PMID- 16980569
TI  - Low-dose methylphenidate actions on tonic and phasic locus coeruleus discharge.
AB  - Methylphenidate (MPH) and other psychostimulants are highly effective in the
      treatment of attention deficit hyperactivity disorder (ADHD). Evidence indicates
      the therapeutic actions of stimulants in ADHD probably involve the locus
      coeruleus (LC)-norepinephrine system. LC neurons display different firing modes
      (tonic and phasic), each associated with distinct behavioral and cognitive
      processes. To date, the impact of low, clinically relevant doses of
      psychostimulants on LC discharge is unknown. The present study examined the
      effects of low-dose MPH on LC tonic and phasic discharge in the halothane
      anesthetized rat. In these studies, MPH produced a dose-dependent suppression of
      tonic and phasic discharge that was relatively modest at the lower doses.
      Nonetheless, these lower doses of MPH suppressed the signal-to-noise ratio of
      excitatory phasic discharge and increased the signal-to-noise ratio of the
      inhibitory component of the phasic response. Largely comparable effects were
      observed with oral and intraperitoneal administration of MPH. Combined, these
      observations indicate relatively modest suppression of LC neuronal discharge
      activity by low-dose MPH and that evoked discharge may be more sensitive than
      tonic activity to the lowest doses of MPH. It is posited that the behavioral
      calming and cognition-enhancing effects of low-dose psychostimulants probably
      involve modest alterations in LC discharge combined with increased catecholamine
      efflux within select forebrain regions (i.e., the prefrontal cortex).

PMID- 16980570
TI  - Acknowledging adult bias: a focus-group approach to utilizing beauty salons as
      health-education portals for inner-city adolescent girls.
AB  - To assess the feasibility of using beauticians as health literacy agents and
      beauty salons as health-education portals for adolescent, inner-city, African
      American girls, the authors conducted focus groups with 25 women: salon clients,
      salon owners, and medical students. Facilitators to program development included
      (a) beautician-client relationships, (b) teens' access to health information, and
      (c) beauticians as information resources. Barriers included (a) adult opinions of
      teen behaviors, (b) teen mistrust of adults, and (c) low health literacy of
      beauticians. In developing a health-education program for this population,
      beauticians and salons may be excellent health information agents and portals if
      barriers including beautician poor health literacy, adolescent mistrust in
      adults, and adults' anti-adolescent bias are improved. Program implementation
      must not solely focus on teens but should also include adult salon users, with
      the goal of reaching the teens first through these adults and, with time and
      trust, reaching the teens directly.

PMID- 16980571
TI  - Drawing from Freirian empowerment methods to develop and use innovative learning
      maps: increasing enrollment of uninsured children on Detroit's eastside.
AB  - In 2001, virtually every child on Detroit's eastside was eligible for health
      coverage, yet approximately 3,000 children remained uninsured. The primary aim of
      the Eastside Access Partnership (EAP), a community-based participatory research
      collaboration, was to increase enrollment of uninsured children in state
      programs. To achieve this aim, one of the approaches that EAP is using is the
      innovative Learning Map titled Choosing the Healthy Path, which was developed in
      collaboration with Root Learning, Inc. Although Learning Maps were originally
      developed to assist corporations in implementing strategic change, their
      integration of visualization and interactive dialogue incorporates Freirian
      principles of empowerment education, making them a viable option for providing
      meaningful learning opportunities for community residents. This article presents
      the collaborative process involving the University of Michigan, local community
      based organizations, community members, and Root Learning consultants to develop
      a visual map that enables community residents to understand and overcome the
      barriers that prevent them from obtaining health insurance for their children.

PMID- 16980572
TI  - Application of a Web-based tailored health risk assessment in a work-site
      population.
AB  - This article presents an examination of the feasibility of implementing a Web
      based tailored health risk assessment (HRA) as part of a University-based work
      site health promotion program. Although the effectiveness of tailoring has been
      well established in the research literature, tailoring health messages for the
      purposes of health promotion and behavior change is only now starting to be used
      and evaluated in real-world settings. Key issues to be examined include the
      feasibility of delivery of a web-based tailored HRA, utility of data gathered for
      program planning, participation rates compared to traditional programming,
      usability, and participant satisfaction with the HRA.

PMID- 16980573
TI  - Change of serum albumin and risk of cardiovascular disease and all-cause
      mortality: Longitudinal Aging Study Amsterdam.
AB  - The aim of this longitudinal study was to investigate 3-year change in serum
      albumin concentration as a determinant of incident cardiovascular disease (CVD)
      and all-cause mortality. Data were from 713 respondents of the Longitudinal Aging
      Study Amsterdam initially aged 55-85 years. Serum albumin was measured at
      baseline (1992/1993) and after 3 years. At the 6-year follow-up, incident CVD
      (among 456 respondents with no prevalent CVD at the 3-year follow-up) and all
      cause mortality were ascertained. Overall, 18.9% developed CVD and 10.9% died.
      After adjustment for potential confounders, a higher level of serum albumin at
      the 3-year follow-up was associated with a lower risk for incident CVD (relative
      risk = 0.88, 95% confidence interval (CI): 0.79, 0.98). The risk of incident CVD
      was 0.88 (95% CI: 0.78, 0.99) per unit (g/liter) increase in change in albumin
      between 3-year follow-up and baseline. Chronic low serum albumin (<or=43 g/liter
      at baseline and 3-year follow-up) was not associated with incident CVD (p =
      0.22). A clinically relevant decrease in serum albumin (>or=1 standard deviation
      (2.5 g/liter) between baseline and 3-year follow-up) tended to be associated with
      a twofold risk (relative risk = 2.00, 95% CI: 0.91, 4.39). For all-cause
      mortality, no associations were observed. These findings suggest that older
      persons with a decrease in serum albumin concentration, even within the normal
      range, might be at increased risk of incident CVD. Change in serum albumin may be
      used as an early marker for CVD risk.

PMID- 16980574
TI  - Schizophrenia and neural tube defects: comparisons from an epidemiological
      perspective.
AB  - In this review, we examine and compare epidemiological studies of schizophrenia
      and neural tube defects (NTDs). Although there is no apparent link between these
      2 disparate disorders in terms of clinical manifestation or phenotypes,
      overlapping patterns in the variation of incidence of schizophrenia with that of
      NTDs indicate the existence of one or more shared etiological risk factors.
      Evidence in support of such a phenomenon may enhance our understanding of
      underlying pathological mechanisms and may guide future studies of etiology and
      prevention. The similarities that occur in a number of epidemiological
      observations for these disorders are in keeping with a hypothesis of nutritional
      deficiencies in utero acting as a risk factor for both schizophrenia and NTDs.
      Programes of periconceptual folate and multivitamin supplementation aimed to
      reduce the risk of NTDs are already in place in many countries. Nevertheless,
      evidence of additional effects of specific maternal micronutrient deficiency on
      risk of schizophrenia may not only increase enthusiasm for expansion of such
      programes but also enhance understanding of etiology of this disorder and offer
      the potential for targeted interventions in high-risk groups.

PMID- 16980575
TI  - Intron size, abundance, and distribution within untranslated regions of genes.
AB  - Most research concerning the evolution of introns has largely considered introns
      within coding sequences (CDSs), without regard for introns located within
      untranslated regions (UTRs) of genes. Here, we directly determined intron size,
      abundance, and distribution in UTRs of genes using full-length cDNA libraries and
      complete genome sequences for four species, Arabidopsis thaliana, Drosophila
      melanogaster, human, and mouse. Overall intron occupancy (introns/exon kbp) is
      lower in 5' UTRs than CDSs, but intron density (intron occupancy in regions
      containing introns) tends to be higher in 5' UTRs than in CDSs. Introns in 5'
      UTRs are roughly twice as large as introns in CDSs, and there is a sharp drop in
      intron size at the 5' UTR-CDS boundary. We propose a mechanistic explanation for
      the existence of selection for larger intron size in 5' UTRs, and outline several
      implications of this hypothesis. We found introns to be randomly distributed
      within 5' UTRs, so long as a minimum required exon size was assumed. Introns in
      3' UTRs were much less abundant than in 5' UTRs. Though this was expected for
      human and mouse that have intron-dependent nonsense-mediated decay (NMD) pathways
      that discourage the presence of introns within the 3' UTR, it was also true for
      A. thaliana and D. melanogaster, which may lack intron-dependent NMD. Our
      findings have several implications for theories of intron evolution and genome
      evolution in general.

PMID- 16980576
TI  - Preferential duplication in the sparse part of yeast protein interaction network.
AB  - Gene duplication is an important mechanism driving the evolution of biomolecular
      network. Thus, it is expected that there should be a strong relationship between
      a gene's duplicability and the interactions of its protein product with other
      proteins in the network. We studied this question in the context of the protein
      interaction network (PIN) of Saccharomyces cerevisiae. We found that duplicates
      have, on average, significantly lower clustering coefficient (CC) than
      singletons, and the proportion of duplicates (PD) decreases steadily with CC.
      Furthermore, using functional annotation data, we observed a strong negative
      correlation between PD and the mean CC for functional categories. By partitioning
      the network into modules and assigning each protein a modularity measure Q(n), we
      found that CC of a protein is a reflection of its modularity. Moreover, the core
      components of complexes identified in a recent high-throughput experiment,
      characterized by high CC, have lower PD than that of the attachments.
      Subsequently, 2 types of hub were identified by their degree, CC and Q(n).
      Although PD of intramodular hubs is much less than the network average, PD of
      intermodular hubs is comparable to, or even higher than, the network average. Our
      results suggest that high CC, and thus high modularity, pose strong evolutionary
      constraints on gene duplicability, and gene duplication prefers to happen in the
      sparse part of PINs.

PMID- 16980577
TI  - Some disassembly required: role of DNA translocases in the disruption of
      recombination intermediates and dead-end complexes.

PMID- 16980578
TI  - Packing for the germy: the role of histone H4 Ser1 phosphorylation in chromatin
      compaction and germ cell development.

PMID- 16980579
TI  - Genetic regulation of bone mass and susceptibility to osteoporosis.
AB  - Osteoporosis is a common disease with a strong genetic component characterized by
      reduced bone mass and increased risk of fragility fractures. Twin and family
      studies have shown that the heritability of bone mineral density (BMD) and other
      determinants of fracture risk-such as ultrasound properties of bone, skeletal
      geometry, and bone turnover-is high, although heritability of fracture is modest.
      Many different genetic variants of modest effect size are likely to contribute to
      the regulation of these phenotypes by interacting with environmental factors such
      as diet and exercise. Linkage studies in rare Mendelian bone diseases have
      identified several previously unknown genes that play key roles in regulating
      bone mass and bone turnover. In many instances, subtle polymorphisms in these
      genes have also been found to regulate BMD in the general population. Although
      there has been extensive progress in identifying the genetic variants that
      regulate susceptibility to osteoporosis, most of the genes and genetic variants
      that regulate bone mass and susceptibility to osteoporosis remain to be
      discovered.

PMID- 16980580
TI  - SAS-mediated acetylation of histone H4 Lys 16 is required for H2A.Z incorporation
      at subtelomeric regions in Saccharomyces cerevisiae.
AB  - The yeast SAS (Something About Silencing) complex and the histone variant H2A.Z
      have both previously been linked to an antisilencing function at the subtelomeric
      regions. SAS is an H4 Lys 16-specific histone acetyltransferase complex. Here we
      demonstrate that the H4 Lys 16 acetylation by SAS is required for efficient H2A.Z
      incorporation near telomeres. The presence of H4 Lys 16 acetylation and H2A.Z
      synergistically prevent the ectopic propagation of heterochromatin. Overall, our
      data suggest a novel antisilencing mechanism near telomeres.

PMID- 16980581
TI  - A cell-type-specific transcriptional network required for estrogen regulation of
      cyclin D1 and cell cycle progression in breast cancer.
AB  - Estrogen stimulates the proliferation of the most common type of human breast
      cancer that expresses estrogen receptor alpha (ERalpha) through the activation of
      the cyclin D1 (CCND1) oncogene. However, our knowledge of ERalpha transcriptional
      mechanisms remains limited. Hence, it is still elusive why ERalpha ectopically
      expressed in ER-negative breast cancer cells (BCC) is functional on ectopic
      reporter constructs but lacks activity on many endogenous target genes, including
      CCND1. Here, we show that estradiol (E2) stimulation of CCND1 expression in BCC
      depends on a novel cell-type-specific enhancer downstream from the CCND1 coding
      region, which is the primary ERalpha recruitment site in estrogen-responsive
      cells. The pioneer factor FoxA1 is specifically required for the active chromatin
      state of this enhancer and as such is crucial for both CCND1 expression and
      subsequent cell cycle progression. Interestingly, even in BCC, CCND1 levels and
      proliferation are tightly controlled by E2 through the establishment of a
      negative feedforward loop involving the induction of NFIC, a putative tumor
      suppressor capable of directly repressing CCND1 transcription. Taken together,
      our results reveal an estrogen-regulated combinatorial network including cell
      specific cis- and trans-regulators of CCND1 expression where ERalpha collaborates
      with other transcription factors associated with the ER-positive breast cancer
      phenotype, including FoxA1 and NFIC.

PMID- 16980582
TI  - The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1beta.
AB  - Although induction of blood vessel growth is acknowledged as a pivotal
      requirement for the evolution of macroscopic tumors, the events that trigger
      onset of tumor angiogenesis remain largely obscure. The pervasive Myc oncoprotein
      is itself a potent inducer of angiogenesis in a wide range of tissues. We have
      used a reversibly switchable mouse transgenic model of Myc-dependent beta-cell
      carcinogenesis to delineate the kinetics and causal sequence of angiogenic
      processes following acute Myc activation. We show that onset of endothelial cell
      proliferation is induced shortly after Myc-induced cell cycle entry of beta
      cells. Endothelial cell proliferation is not indirectly induced by local tissue
      hypoxia but instead via a diffusible angiogenic signal produced by Myc-expressing
      beta cells. This signal triggers the release of pre-existing, sequestered VEGF
      from the islet extracellular matrix, that then homes to the endothelial
      compartment where it induces endothelial cell proliferation. Myc activation in
      beta cells rapidly induces expression and release of the proinflammatory cytokine
      interleukin 1beta (IL-1beta). We show that IL-1beta is the principal effector
      downstream of Myc responsible for triggering rapid onset of islet angiogenesis.
      Together, our data delineate a complete pathway in vivo by which the highly
      pleiotropic Myc oncoproteins elicits coexpansion of the vascular compartment
      during tumorigenic progression.

PMID- 16980583
TI  - The C-terminal tail of the Hedgehog receptor Patched regulates both localization
      and turnover.
AB  - Patched (Ptc) is a membrane protein whose function in Hedgehog (Hh) signal
      transduction has been conserved among metazoans and whose malfunction has been
      implicated in human cancers. Genetic analysis has shown that Ptc negatively
      regulates Hh signal transduction, but its activity and structure are not known.
      We investigated the functional and structural properties of Drosophila Ptc and
      its C-terminal domain (CTD), 183 residues that are predicted to reside in the
      cytoplasm. Our results show that Ptc, as well as truncated Ptc deleted of its
      CTD, forms a stable trimer. This observation is consistent with the proposal that
      Ptc is structurally similar to trimeric transporters. The CTD itself trimerizes
      and is required for both Ptc internalization and turnover. Two mutant forms of
      the CTD, one that disrupts trimerization and the other that mutates the target
      sequence of the Nedd4 ubiquitin ligase, stabilize Ptc but do not prevent
      internalization and sequestration of Hh. Ptc deleted of its CTD is stable and
      localizes to the plasma membrane. These data show that degradation of Ptc is
      regulated at a step subsequent to endocytosis, although endocytosis is a likely
      prerequisite. We also show that the CTD of mouse Ptc regulates turnover.

PMID- 16980584
TI  - CKI and CKII mediate the FREQUENCY-dependent phosphorylation of the WHITE COLLAR
      complex to close the Neurospora circadian negative feedback loop.
AB  - The eukaryotic circadian oscillators consist of circadian negative feedback
      loops. In Neurospora, it was proposed that the FREQUENCY (FRQ) protein promotes
      the phosphorylation of the WHITE COLLAR (WC) complex, thus inhibiting its
      activity. The kinase(s) involved in this process is not known. In this study, we
      show that the disruption of the interaction between FRQ and CK-1a (a casein
      kinase I homolog) results in the hypophosphorylation of FRQ, WC-1, and WC-2. In
      the ck-1a(L) strain, a knock-in mutant that carries a mutation equivalent to that
      of the Drosophila dbt(L) mutation, FRQ, WC-1, and WC-2 are hypophosphorylated.
      The mutant also exhibits ~32 h circadian rhythms due to the increase of FRQ
      stability and the significant delay of FRQ progressive phosphorylation. In
      addition, the levels of WC-1 and WC-2 are low in the ck-1a(L) strain, indicating
      that CK-1a is also important for the circadian positive feedback loops. In spite
      of its low accumulation in the ck-1a(L) strain, the hypophosphorylated WCC
      efficiently binds to the C-box within the frq promoter, presumably because it
      cannot be inactivated through FRQ-mediated phosphorylation. Furthermore, WC-1 and
      WC-2 are also hypophosphorylated in the cka(RIP) strain, which carries the
      disruption of the catalytic subunit of casein kinase II. In the cka(RIP) strain,
      WCC binding to the C-box is constantly high and cannot be inhibited by FRQ
      despite high FRQ levels, resulting in high levels of frq RNA. Together, these
      results suggest that CKI and CKII, in addition to being the FRQ kinases, mediate
      the FRQ-dependent phosphorylation of WCs, which inhibit their activity and close
      the circadian negative feedback loop.

PMID- 16980585
TI  - A novel histone deacetylase pathway regulates mitosis by modulating Aurora B
      kinase activity.
AB  - Histone deacetylase (HDAC) inhibitors perturb the cell cycle and have great
      potential as anti-cancer agents, but their mechanism of action is not well
      established. HDACs classically function as repressors of gene expression,
      tethered to sequence-specific transcription factors. Here we report that HDAC3 is
      a critical, transcription-independent regulator of mitosis. HDAC3 forms a complex
      with A-Kinase-Anchoring Proteins AKAP95 and HA95, which are targeted to mitotic
      chromosomes. Deacetylation of H3 in mitosis requires AKAP95/HA95 and HDAC3 and
      provides a hypoacetylated H3 tail that is the preferred substrate for Aurora B
      kinase. Phosphorylation of H3S10 by Aurora B leads to dissociation of HP1
      proteins from methylated H3K9 residues on mitotic heterochromatin. This
      transcription-independent pathway, involving interdependent changes in histone
      modification and protein association, is required for normal progression through
      mitosis and is an unexpected target of HDAC inhibitors, a class of drugs
      currently in clinical trials for treating cancer.

PMID- 16980586
TI  - Phosphorylation of histone H4 Ser1 regulates sporulation in yeast and is
      conserved in fly and mouse spermatogenesis.
AB  - Sporulation in Saccharomyces cerevisiae is a highly regulated process wherein a
      diploid cell gives rise to four haploid gametes. In this study we show that
      histone H4 Ser1 is phosphorylated (H4 S1ph) during sporulation, starting from mid
      sporulation and persisting to germination, and is temporally distinct from
      earlier meiosis-linked H3 S10ph involved in chromosome condensation. A histone H4
      S1A substitution mutant forms aberrant spores and has reduced sporulation
      efficiency. Deletion of sporulation-specific yeast Sps1, a member of the Ste20
      family of kinases, nearly abolishes the sporulation-associated H4 S1ph
      modification. H4 S1ph may promote chromatin compaction, since deletion of SPS1
      increases accessibility to antibody immunoprecipitation; furthermore, either
      deletion of Sps1 or an H4 S1A substitution results in increased DNA volume in
      nuclei within spores. We find H4 S1ph present during Drosophila melanogaster and
      mouse spermatogenesis, and similar to yeast, this modification extends late into
      sperm differentiation relative to H3 S10ph. Thus, H4 S1ph may be an
      evolutionarily ancient histone modification to mark the genome for gamete
      associated packaging.

PMID- 16980587
TI  - Tid1/Rdh54 promotes dissociation of Dmc1 from nonrecombinogenic sites on meiotic
      chromatin.
AB  - The meiosis-specific recombinase Dmc1 plays a critical role in DNA strand
      exchange in budding yeast. Tid1/Rdh54, a member of the Swi2/Snf2 family of DNA
      translocases, has been shown to stimulate Dmc1-dependent recombination. Tid1and
      its budding yeast paralog Rad54 have a variety of biochemical activities that may
      contribute to their biological function. Here we demonstrate that Dmc1 can
      associate with chromatin in the absence of DNA double-strand breaks (DSBs), and
      Tid1 suppresses this association. Chromatin immunoprecipitation experiments
      indicate that an activity shared by Tid1 and Rad54 is required for normal
      assembly of Dmc1 at DSB sites in preparation for recombination. These results
      lead to a model in which the ATP hydrolysis-dependent DNA translocase activity of
      Tid1 acts to promote dissociation of Dmc1 from nonreombinogenic sites on
      chromatin, with Rad54 being able to substitute for this function in the absence
      of Tid1. The tendency of Dmc1 to form unproductive interactions with chromatin is
      proposed to be a consequence of the mechanism of strand exchange. The results
      raise the possibility that ATP hydrolysis-dependent disruption of nonproductive
      recombinase-DNA interactions is a feature shared with other homologous
      recombination systems.

PMID- 16980588
TI  - Identification of a novel regulatory protein (CsrD) that targets the global
      regulatory RNAs CsrB and CsrC for degradation by RNase E.
AB  - In Escherichia coli, the global regulatory protein CsrA (carbon store regulator
      A) binds to leader segments of target mRNAs, affecting their translation and
      stability. CsrA activity is regulated by two noncoding RNAs, CsrB and CsrC, which
      act by sequestering multiple CsrA dimers. Here, we describe a protein (CsrD) that
      controls the degradation of CsrB/C RNAs. The dramatic stabilization of CsrB/C
      RNAs in a csrD mutant altered the expression of CsrA-controlled genes in a manner
      predicted from the previously described Csr regulatory circuitry. A deficiency in
      RNase E, the primary endonuclease involved in mRNA decay, also stabilized CsrB/C,
      although the half-lives of other RNAs that are substrates for RNase E (rpsO,
      rpsT, and RyhB) were unaffected by csrD. Analysis of the decay of CsrB RNA, both
      in vitro and in vivo, suggested that CsrD is not a ribonuclease. Interestingly,
      the CsrD protein contains GGDEF and EAL domains, yet unlike typical proteins in
      this large superfamily, its activity in the regulation of CsrB/C decay does not
      involve cyclic di-GMP metabolism. The two predicted membrane-spanning regions are
      dispensable for CsrD activity, while HAMP-like, GGDEF, and EAL domains are
      required. Thus, these studies demonstrate a novel process for the selective
      targeting of RNA molecules for degradation by RNase E and a novel function for a
      GGDEF-EAL protein.

PMID- 16980589
TI  - Pdm and Castor specify late-born motor neuron identity in the NB7-1 lineage.
AB  - Embryonic development requires generating cell types at the right place (spatial
      patterning) and the right time (temporal patterning). Drosophila neuroblasts
      undergo stem cell-like divisions to generate an ordered sequence of neuronal
      progeny, making them an attractive system to study temporal patterning. Embryonic
      neuroblasts sequentially express Hunchback, Kruppel, Pdm1/Pdm2 (Pdm), and Castor
      (Cas) transcription factors. Hunchback and Kruppel specify early-born temporal
      identity, but the role of Pdm and Cas in specifying temporal identity has never
      been addressed. Here we show that Pdm and Cas regulate late-born motor neuron
      identity within the NB7-1 lineage: Pdm specifies fourth-born U4 motor neuron
      identity, while Pdm/Cas together specify fifth-born U5 motor neuron identity. We
      conclude that Pdm and Cas specify late-born neuronal identity; that Pdm and Cas
      act combinatorially to specify a temporal identity distinct from either protein
      alone, and that Cas repression of pdm expression regulates the generation of
      neuronal diversity.

PMID- 16980590
TI  - Endothelial lipase is associated with inflammation in humans.
AB  - The aim of this study was to investigate the extent to which inflammation is
      linked with plasma endothelial lipase (EL) concentrations among healthy sedentary
      men. Plasma C-reactive protein (CRP) concentrations were measured with a highly
      sensitive commercial immunoassay, plasma interleukin-6 (IL-6) concentrations were
      measured using a commercial ELISA, and plasma secretory phospholipase A(2) type
      IIA (sPLA(2)-IIA) concentrations were measured using a commercial assay in a
      sample of 74 moderately obese men (mean body mass index, 29.8 +/- 5.2 kg/m(2)).
      Plasma EL concentrations were positively correlated with various indices of
      obesity, fasting plasma insulin, and plasma CRP, IL-6, and sPLA(2)-IIA
      concentrations. Multiple regression analyses revealed that plasma CRP
      concentrations explained 14.5% (P = 0.0008) of the variance in EL concentrations.
      When entered into the model, LPL activity accounted for 16.1% (P < 0.0001) and
      plasma CRP concentrations accounted for 20.9% (P < 0.0001) of the variance in EL
      concentrations. The combined impact of visceral adipose tissue (VAT) and of an
      inflammation score on EL concentrations was investigated. Among subjects with
      high or low VAT, those having a high inflammation score based on plasma CRP, IL
      6, and sPLA(2)-IIA concentrations had increased plasma EL concentrations (P =
      0.0005). In conclusion, our data reveal a strong association between
      proinflammatory cytokines and plasma EL concentrations among healthy people with
      low or high VAT levels.

PMID- 16980591
TI  - Molecular genetic studies of the memory of winter.
AB  - Many plant species have evolved the ability to flower in the proper season by
      sensing environmental cues. The prolonged cold of winter is one such cue that
      certain plants use to acquire competence to flower the following spring. For
      example, biennials and winter annuals become established in one growing season
      and often flower quickly in the early spring of the following year to complete
      their life cycles. The process by which exposure to prolonged cold establishes
      competence to flower is known as vernalization. Many studies, starting with the
      classic work of Lang and Melchers, have shown that the vernalized state can be
      stable; i.e. after exposure to cold has ended, competence to flower, in certain
      species, can persist for many months and throughout many cell divisions in the
      shoot apical meristem. Thus, plants can exhibit a 'memory of winter' and
      vernalization can result in an epigenetic switch in the classic sense of the
      term: a change that is stable in the absence of the inducing signal. The nature
      of this epigenetic switch in Arabidopsis thaliana is discussed here.

PMID- 16980592
TI  - Monitoring plant and soil water status: established and novel methods revisited
      and their relevance to studies of drought tolerance.
AB  - In all studies of the effects of water deficits on plant functioning there is a
      need for an accurate and comprehensive definition of treatments and their effects
      on plant water status. The various measures of water status used in plant and
      soil science are reviewed and their appropriateness for different purposes such
      as for studies of mechanistic effects of water deficits on plants, for breeding
      of drought-tolerant plants, or for management of irrigation systems are reviewed.
      An important conclusion is that the frequent emphasis on water potential rather
      than on cell turgor can be shown to be misleading, as can be measurements in the
      leaf. The disadvantages of the current trend towards the omission of necessary
      water-status measurements, especially common in more molecular studies, are
      outlined, and recommendations made for minimal sets of measurements for specific
      types of experiments.

PMID- 16980593
TI  - Structural and functional compartmentalization in pollen tubes.
AB  - Eukaryotic cellular functions are achieved by concerted activities in the cytosol
      and functions compartmentalized in the nucleus and other membrane-bound
      organelles. Moreover, the cytosol and nucleoplasm are populated with mega
      molecular ensembles that are specialized for different metabolic and biochemical
      processes. Pollen tubes are unique plant cells with a dramatic growth polarity.
      Tube growth is restricted to the tip and is supported by a polarized cytoplasmic
      organization. The apical region of elongating pollen tubes is a domain occupied
      exclusively by transport vesicles to support the secretion and endocytic activity
      needed for the rapid cell expansion at the apex. Larger organelles are
      predominantly segregated to the cytoplasm distal to the subapical region.
      Underlying the organelle compartmentalization is an elaborate actin cytoskeleton
      with distinct structural and dynamics properties at the tip, in the subapical
      region, and in the cytoplasm subtending it. Cytoplasmic domains with differential
      ionic conditions and spatially restricted localization of molecules in pollen
      tubes may also be important for regulating the polar cell growth process. The
      polarized cellular organization in pollen tubes drives an extremely efficient
      cell growth process that is responsive to extracellular signals, including
      directional cues. It may be an amplified framework of the cytoplasmic
      architecture that supports growth in other plant cell types that involves
      considerably more subtle and transient differential cell expansion.

PMID- 16980594
TI  - Light signals and flowering.
AB  - Physiological studies over a long period have shown that light acts to regulate
      flowering through the three main variables of quality, quantity, and duration.
      Intensive molecular genetic and genomic studies with the model plant Arabidopsis
      have given considerable insight into the mechanisms involved, particularly with
      regard to quality and photoperiod. For photoperiodism light, acting through
      phytochromes and cryptochromes, the main photomorphogenetic photoreceptors, acts
      to entrain and interact with a circadian rhythm of CONSTANS (CO) expression
      leading to transcription of the mobile floral integrator, FLOWERING LOCUS T (FT).
      The action of phytochromes and cryptochromes in photoperiodism is augmented by
      ZEITLUPE (ZTL) and FLAVIN-BINDING, KELCH REPEAT, F-BOX (FKF1) acting as accessory
      photoreceptors on entrainment and interaction, respectively. Light quality acts
      independently of the circadian system through Phytochromes B, D, and E to
      regulate FT. Light quantity effects, on the other hand, are still incompletely
      understood but are likely to be linked either directly or indirectly to patterns
      of assimilate partitioning and resource utilization within the plant.

PMID- 16980595
TI  - Down-regulation of sorbitol dehydrogenase and up-regulation of sucrose synthase
      in shoot tips of the transgenic apple trees with decreased sorbitol synthesis.
AB  - Both sorbitol and sucrose are translocated to, and utilized in, sink tissues of
      apple (Malus domestica). Considering that antisense suppression of aldose 6
      phosphate reductase resulted in lower concentrations of sorbitol and higher
      concentrations of sucrose in source leaves without altering the vegetative growth
      of apple trees, it was hypothesized that sorbitol metabolism is down-regulated
      and sucrose metabolism is up-regulated in shoot tips of the transgenic plants.
      Carbohydrate measurements indicated that sorbitol concentration was lower whereas
      sucrose concentration was higher in the shoot tips of transgenic apple plants
      with decreased sorbitol synthesis compared with the untransformed control.
      However, the shoot relative growth rate was not altered in the transgenic plants.
      Sorbitol dehydrogenase (SDH) activity was decreased; acid invertase activity and
      neutral invertase activity remained the same, whereas sucrose synthase (SUSY)
      activity was increased in shoot tips of the transgenic plants. The SDH transcript
      level was lower whereas the SUSY transcript level was higher in shoot tips of the
      transgenic plants. SDH activity and SDH transcript level were specifically
      stimulated by exogenous sorbitol fed to the shoot tips via the transpiration
      stream but were specifically inhibited by sucrose. SUSY activity and SUSY
      transcript level were dramatically enhanced by sucrose, but decreased by glucose
      and fructose. Neither acid invertase nor neutral invertase activity responded to
      sucrose, glucose, fructose, or any other sugars tested. It is concluded that
      sorbitol dehydrogenase is down-regulated, whereas sucrose synthase is up
      regulated in shoot tips of the transgenic apple trees with decreased sorbitol
      synthesis, leading to homeostasis of vegetative growth. Sorbitol and sucrose act
      as signal molecules to modulate the expression and activities of sorbitol
      dehydrogenase and sucrose synthase, both of which play an important role in
      determining the sink strength of apple shoot tips.

PMID- 16980596
TI  - Salinity tolerance of 'Valencia' orange trees on rootstocks with contrasting salt
      tolerance is not improved by moderate shade.
AB  - The effects of shading in combination with salinity treatments were studied in
      citrus trees on two rootstocks with contrasting salt tolerance to determine if
      shading could reduce the negative effects of salinity stress. Well-nourished 2
      year-old 'Valencia' orange trees grafted on Cleopatra mandarin (Cleo, relatively
      salt tolerant) or Carrizo citrange (Carr, relatively salt sensitive), were grown
      either under a 50% shade cloth or left unshaded in full sunlight. Half the trees
      received no salinity treatment and half were salinized with 50 mM Cl- during two
      9 week salinity periods in the spring and autumn interrupted by an 11 week rainy
      period. The shade treatment reduced midday leaf temperature and leaf-to-air
      vapour pressure deficit regardless of salinity treatments. In non-salinized
      trees, shade increased midday CO2 assimilation rate (A(CO2)) and stomatal
      conductance, but had no effect on leaf transpiration (E(lf)). Shade also
      increased leaf chlorophyll and photosynthetic water use efficiency (A(CO2)/E(lf))
      in leaves on both rootstocks and increased total plant dry weight in Cleo. The
      salinity treatment reduced leaf growth and leaf gas exchange parameters. Shade
      decreased Cl- concentrations in leaves of salinized Carr trees, but had no effect
      on leaf or root Cl- of trees on Cleo. There were no significant differences in
      leaf gas exchange parameters of shaded and unshaded salinized plants but the
      growth reduction from salinity stress was actually greater for shaded than for
      unshaded trees. Shaded trees on both rootstocks had higher leaf Na+ than unshaded
      trees after the first salinity period, and this shade-induced elevated leaf Na+
      persisted after the second salinity period in trees on Carr. Thus, shading did
      not alleviate the negative effects of salinity on growth and Na+ accumulation.

PMID- 16980597
TI  - An open-label, fixed-dose study of bupropion effect on sexual function scores in
      women treated for breast cancer.
AB  - BACKGROUND: Sexual morbidity after chemotherapy and hormonal therapy for breast
      cancer can seriously affect patients' quality of life. Bupropion is an
      antidepressant that has been reported to increase libido. OBJECTIVE: To
      investigate the improvement of sexual function in female breast cancer patients
      using bupropion. PATIENTS AND METHODS: We performed an 8-week open trial using
      bupropion in women diagnosed with breast cancer who had received chemotherapy and
      were currently receiving adjunctive hormonal therapy. The Arizona Sexual
      Experience Scale (ASEX) was used. The ASEX scale includes five questions that
      evaluate sexual function in the following areas: libido, excitability and ability
      to reach orgasm. Women received oral Bupropion 150 mg/daily for 8 weeks and were
      evaluated prior to the initiation of the study and again during Weeks 4 and 8.
      RESULTS: Twenty patients were included in the study. At the beginning of the
      study, the mean ASEX score was 23.45 [21.67-25.24] 95% CI. After 4 weeks of
      treatment, we observed a reduction in the mean ASEX score that persisted until
      the end of the study, at eight weeks: 18.45 [16.59-20.31] 95% CI (P = 0.0003) and
      18.95 [16.60-21.30] 95% CI (P = 0.0024), respectively. CONCLUSION: In this non
      controlled open trial bupropion 150 mg/daily was associated with improved sexual
      function in women receiving adjuvant systemic treatment for breast cancer.

PMID- 16980598
TI  - Thyroid transcription factor 1--a new prognostic factor in lung cancer: a meta
      analysis.
AB  - BACKGROUND: The aim of this study was to determine the prognostic role for
      survival of thyroid transcription factor 1 (TTF-1) in lung cancer. METHODS:
      Studies evaluating survival and TTF-1 in lung cancer patients, published until
      August 2005, were assessed with a methodological scoring system. The required
      data for estimation of individual hazard ratios (HRs) for survival were extracted
      from the publications and a combined HR was calculated. RESULTS: We identified 10
      eligible papers, all dealing with non-small-cell lung cancer (NSCLC). Eight were
      meta-analysed (evaluable studies). Seven studies included patients with local
      and/or locoregional diseases and three dealt only with adenocarcinoma. Median
      methodological quality score was 65.9% (range = 31.8%-70.5%). TTF-1 positivity
      was associated with statistically significant reduced or improved survival in one
      and four studies, respectively. Combined HR for the eight evaluable studies was
      0.64 [95% confidence interval (CI) = 0.41-1.00]. In the subgroup of
      adenocarcinoma, the combined HR was 0.53 (95% CI = 0.29-0.95). CONCLUSION: TTF-1
      is a good prognostic factor for survival in NSCLC. Its effect appears also
      significant when the analysis is restricted to patients with adenocarcinoma. This
      study supports the fact that TTF-1 could be included in further prospective
      trials studying prognostic factors in NSCLC.

PMID- 16980599
TI  - Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed
      or refractory multiple myeloma: safety and efficacy.
AB  - BACKGROUND: Lenalidomide is active and well tolerated in relapsed and refractory
      multiple myeloma. We conducted a phase I/II trial of the combination of
      lenalidomide and chemotherapy to evaluate the safety and efficacy of the
      combination. METHODS: The 62 patients enrolled received liposomal doxorubicin 40
      mg/m(2) i.v. and vincristine 2 mg i.v. on day 1, dexamethasone 40 mg p.o. on days
      1-4 (DVd), and lenalidomide on days 1-21 in 28-day cycles. Primary end points
      were maximum tolerated dose (MTD) of lenalidomide with DVd chemotherapy and
      overall response rate (ORR) by Southwest Oncology Group criteria of the
      combination. FINDINGS: The median age was 62 years, 70% of patients were males
      and 65% had refractory multiple myeloma. The MTD of lenalidomide with DVd
      chemotherapy was 10 mg and the dose-limiting toxicity was non-neutropenic sepsis.
      After 7.5 months of median follow-up, the ORR of the combination was 75%, with
      29% of patients achieving a complete or near complete remission. The median
      progression-free survival was 12 months, while the median overall survival has
      not yet been reached. INTERPRETATION: The combination of lenalidomide and DVd
      chemotherapy was well tolerated and resulted in high response rates in this
      mostly refractory patient population. Evaluation of this combination in newly
      diagnosed patients is warranted.

PMID- 16980600
TI  - 18F-Fluoro-deoxy-glucose positron emission tomography in lymphoma of mucosa
      associated lymphoid tissue: histology makes the difference.
AB  - BACKGROUND: The usefulness of 2-[fluorine-18]fluoro-2-deoxy-D-glucose Positron
      emission tomography (18F-FDG-PET) in lymphoma of mucosa-associated lymphoid
      tissue (MALT lymphoma) is still a matter of debate, and conflicting results have
      been reported. We have evaluated whether the histological feature of plasmacytic
      differentiation (PD) might explain the heterogeneous behavior of MALT lymphoma
      regarding 18F-FDG uptake. PATIENTS AND METHODS: A total of 35 patients with a
      diagnosis of MALT lymphoma referred to our PET unit were studied. Whole-body 18F
      FDG-PET scans were carried out on a General Electrics advanced PET scanner 40 min
      after i.v. injection of 300-380 MBq 18F-FDG. Images were reconstructed
      iteratively. In areas with focally elevated FDG uptake, standard uptake values
      (SUVs) were calculated. RESULTS: A total of 19 patients had MALT lymphoma with
      plasmacytic differentiation (pMALT), while MALT lymphoma without plasmacytic
      features was diagnosed in 16 patients. Sixteen of 19 patients with PD showed
      significant 18F-FDG uptake in involved sites (SUV: 3.5-11.7). By contrast, 13 of
      16 patients with normal MALT lymphoma showed a false-negative 18F-FDG-PET result.
      Two of these patients disclosed no tracer uptake in the majority of involved
      sites apart from one single lesions, while three had a true-positive 18F-FDG-PET
      scan (SUV: 3.4-6.0). CONCLUSIONS: 18F-FDG-PET visualizes pMALT in a high
      proportion of patients, whereas FDG-PET results are significantly less reliable
      in typical MALT (P = 0.001). This finding may partly account for the
      heterogeneous results of 18F-FDG-PET-studies in MALT lymphoma.

PMID- 16980601
TI  - Temozolomide in combination with celecoxib in patients with advanced melanoma. A
      phase II study of the Hellenic Cooperative Oncology Group.
AB  - BACKGROUND: There is now increasing evidence that a constitutive expression of
      cyclooxygenase (COX)-2 plays a role in the development and progression of
      malignant epithelial tumors. Expression of COX-2 is seen in 93% of melanomas, as
      determined by immunohistochemistry. Temozolomide (TMZ) has demonstrated activity
      against melanoma and has been investigated as single agent or in combination. We
      designed a phase II study to assess the efficacy and toxicity of the combination
      of TMZ and celecoxib (a COX-2 inhibitor) in patients with advanced melanoma.
      PATIENTS AND METHODS: From January 2003 to July 2004, 52 patients were enrolled
      in the study. Nineteen patients were M1a, six M1b and 27 M1c. Patients received
      TMZ 200 mg/m(2) per day p.o. for 5 consecutive days every 4 weeks and celecoxib
      400 mg b.i.d. p.o. for a maximum of six cycles. Celecoxib was continued until
      progression. RESULTS: The median age was 63 years. There were 29 males and 23
      females. Among 50 assessable patients, there were 11 (21.5%) objective responses
      including five complete responses and six partial responses. Twenty patients
      (38.5%) had stabilization of their disease, and 19 (36.5%) progressed. The median
      time to progression was 4.6 months and the median survival 9.5 months. Twenty-two
      patients (41.5%) completed all cycles of treatment. Median relative dose
      intensity of TMZ was 0.99 (range 0.6-1.2). Most commonly seen toxic effects
      included anemia (27.5%), neutropenia (17.5%), thrombocytopenia (33%),
      nausea/vomiting (75%), gastrointestinal (52%) and fatigue (46.5%). One patient
      discontinued due to severe toxicity. COX-2 was determined by immunohistochemistry
      and was expressed in all cases. CONCLUSION: The combination of TMZ and celecoxib
      is safe and potentially effective in the treatment of metastatic melanoma.
      Randomized studies are needed to explore the role of celecoxib in combination
      with chemotherapy or as maintenance treatment in these patients.

PMID- 16980602
TI  - Clinical outcome of adjuvant endocrine treatment according to PR and HER-2 status
      in early breast cancer.
AB  - Patients with estrogen receptor (ER)+/progesterone receptor (PR)- and/or HER-2
      overexpressing breast carcinomas may derive lower benefit from endocrine
      treatment. We examined retrospectively data from 972 breast cancer patients who
      received tamoxifen (725), tamoxifen + Gn-RH analogs (127) and aromatase
      inhibitors (120) as adjuvant treatments. ER+/PR- versus ER+/PR+ tumours were
      characterised by larger size (P = 0.001), higher tumour grade (P = 0.001), higher
      Ki-67 expression (P = 0.001) and lower mean ER (P = 0.000) and HER-2 expression
      (P = 0.000). At univariate analysis, tumour grading [hazard ratio (HR) = 4.0; 95%
      confidence interval (CI) = 1.4-11.1; P = 0.007], nodal status (HR = 3.4; 95% CI
      1.2-5.7; P = 0.000), tumour diameter (HR = 2.9; 95% CI 1.7-4.7; P = 0.000) lack
      of PR expression (HR = 2.1; 95% CI 1.3-3.4; P = 0.002) and HER-2 overexpression
      (HR = 1.9; 95% CI 1.0-3.5; P = 0.03), as well as Ki 67 expression (HR = 1.7; 95%
      CI 1.0-2.7; P = 0.04) were associated with shorter disease-free survival (DFS).
      At the multivariate analysis, nodal status (HR = 3.6; 95% CI 1.9-6.8; P =
      0.0001), lack of PR expression (HR = 2.3; 95% CI 1.3-4.0; P = 0.003) and tumour
      diameter (HR = 2.1; 95% CI 1.1-3.8; P = 0.018) retained their prognostic
      significance, whereas HER-2 overexpression was associated with a trend towards
      shorter DFS that was of borderline statistical significance (HR = 2.0; 95 % CI
      1.0-3.9; P = 0.05). Our data suggest that lack of PR expression and HER-2
      overexpression are both associated with aggressive tumour features, but the
      prognostic information of PR status on the risk of recurrence in endocrine
      treated breast cancer patients is stronger.

PMID- 16980603
TI  - An induction dose of epoetin alpha of 40 000 IU daily for three consecutive days
      increases and maintains hemoglobin levels in anemic cancer patients undergoing
      chemotherapy.
AB  - BACKGROUND: This pilot study was conducted to evaluate the feasibility, activity,
      and safety of an induction dose of epoetin alpha in cancer patients with moderate
      or severe anemia who were receiving chemotherapy. PATIENTS AND METHODS: Thirty
      patients with solid tumors and hemoglobin (Hb) levels <11.0 g/dl were enrolled.
      Patients received single s.c. injections of epoetin alpha, 40 000 IU for three
      consecutive days, and were then observed for the following 30 days. The primary
      efficacy variable was the response rate (Hb increase > or=1 g/dl) at day 15.
      Secondary efficacy variables included the proportion of patients given blood
      transfusions between baseline and the end of study, the duration of response (Hb
      level > or=1 g/dl), and ability to maintain the planned chemotherapy dose (dose
      intensity). RESULTS: At day 15, 23 of 30 (77%) patients had achieved increases in
      Hb levels of at least 1 g/dl. The mean Hb increase in responders was 2.0 g/dl
      [95% confidence interval (CI) = 1.7-2.3 g/dl]. The Hb increase was 2.3 +/- 0.7
      g/dl in responders with baseline Hb levels <9.5 g/dl (median Hb value), and 1.7
      +/- 0.6 g/dl in those with higher Hb levels (P = 0.012). The median duration of
      response was 6.1 weeks (95% CI = 1.6-10.6 weeks). Hematologic parameters were not
      significantly changed in nonresponders. Multivariate analysis detected no
      significant differences in Hb increase at day 15 on the basis of age, sex,
      weight, baseline Hb levels, type or stage of tumor, or treatment with platinum
      based chemotherapy. No serious adverse event related to epoetin alpha treatment
      was observed. CONCLUSIONS: We conclude that a higher initial dosing of epoetin
      alpha appears to be an efficient schedule for treating anemia in cancer patients
      undergoing chemotherapy, conferring higher response rates than those seen with
      standard doses. Further evaluation of these and other epoetin alpha dosage
      regimens is warranted.

PMID- 16980604
TI  - A phase I safety, pharmacological and biological study of the farnesyl protein
      transferase inhibitor, tipifarnib and capecitabine in advanced solid tumors.
AB  - BACKGROUND: To evaluate the toxicity and pharmacological and biological
      properties of the farnesyl protein transferase (FPTase) inhibitor, tipifarnib
      (R115777, ZARNESTRAtrade mark) and capecitabine administered for 14 days every 3
      weeks. PATIENTS AND METHODS: Patients with advanced cancers received twice daily
      tipifarnib (100-500 mg) and capecitabine (1000-1125 mg/m(2)) for 14 days every 3
      weeks. Pharmacokinetics of tipifarnib, capecitabine and 5-fluorouracil (5-FU)
      were determined. Peripheral blood mononuclear cells were analyzed for
      farnesylation of the HDJ2 chaperone protein and FPTase activity. RESULTS: Forty
      one patients received 185 courses of treatment. Diarrhea and palmar-plantar
      erythrodysesthesia were dose limiting at 300 mg tipifarnib/1125 mg/m(2)
      capecitabine b.i.d. When the capecitabine dose was fixed at 1000 mg/m(2) b.i.d.,
      neutropenia was dose limiting at 400 and 500 mg b.i.d. of tipifarnib.
      Capecitabine did not affect the pharmacology of tipifarnib at 100-300 mg b.i.d.,
      although tipifarnib significantly increased the C(max) of 5-FU at 400 mg b.i.d.
      HDJ2 farnesylation and FPTase activity decreased between 200 and 400 mg b.i.d.
      doses of tipifarnib, without a dose-response relationship. Five patients
      demonstrated partial remissions and 11 patients maintained prolonged stable
      disease. CONCLUSIONS: Tipifarnib and capecitabine are well tolerated at 300
      mg/1000 mg/m(2) b.i.d., respectively, resulting in biologically relevant plasma
      concentrations and antitumor activity. The recommended dose for further disease
      focused studies is 300 mg b.i.d. tipifarnib and 1000 mg/m(2) b.i.d. capecitabine,
      given for 14 days every 3 weeks.

PMID- 16980605
TI  - Concurrent radiotherapy and capecitabine, followed by high-dose methotrexate
      consolidation, provided effective palliation in a patient with leptomeningeal
      metastases from breast cancer.

PMID- 16980606
TI  - ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival
      in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine.
AB  - BACKGROUND: Pivotal studies indicate a role of excision repair cross
      complementation 1 (ERCC1) gene and ribonucleotide reductase M1 (RRM1) gene in
      conferring a differential sensitivity to cytotoxic chemotherapy and epidermal
      growth factor receptor (EGFR) gene has been recently extensively investigated in
      non-small-cell lung cancer (NSCLC). DESIGN: Formalin-fixed, paraffin-embedded
      bronchoscopic/fine needle aspiration biopsies obtained from 70 patients with
      advanced NSCLC were retrospectively collected to investigate the expression level
      of ERCC1, RRM1 and EGFR by real-time PCR. Sufficient amounts of messenger RNA
      (mRNA) were successfully extracted from 61 (87%) specimens, reverse transcribed
      and amplified with intron-spanning primers. Forty-one patients had stage IV
      disease and 43 received cisplatin/gemcitabine chemotherapy. RESULTS: A strong
      correlation between ERCC1 and RRM1 mRNA levels (r(s) = 0.624, P < 0.0001) was
      found. Median survival time in patients with low ERCC1 was significantly longer
      (17.3 versus 10.9, P = 0.0032 log-rank test) as well as in patients with low RRM1
      (13.9 versus 10.9, P = 0.0390 log-rank test). Concomitant low expression levels
      of ERCC1 and RRM1 (n = 33) were predictive of a better outcome (14.9 versus 10.0,
      P = 0.0345 log-rank test). Among cisplatin-treated patients, a low ERCC1 level
      was highly predictive of a longer survival (23.0 versus 12.4, P = 0.0001 log-rank
      test). No correlation between gene expression levels and histology was reported.
      No significant correlation between EGFR expression level and survival was found.
      At multivariate analysis, performance status, response to chemotherapy, presence
      of weight loss and ERCC1 were independent prognostic factors for survival.
      CONCLUSIONS: This retrospective study further validates ERCC1 and RRM1 genes as
      reliable candidates for customized chemotherapy and shows a higher impact on the
      survival of NSCLC patients treated with cisplatin/gemcitabine for ERCC1.
      Prospective pharmacogenomic studies represent a research priority in early and
      advanced NSCLC.

PMID- 16980607
TI  - Mitogen-activated protein kinase-mediated disruption of enhancer-promoter
      communication inhibits hepatocyte nuclear factor 4alpha expression.
AB  - Hepatocyte nuclear factor 4 (HNF-4) is a key member of the transcription factor
      network regulating hepatocyte differentiation and function. Activation of the HNF
      4 gene involves physical interaction between a distant enhancer and the proximal
      promoter region, bound by distinct sets of transcription factors. Here we report
      that, upon mitogen-activated protein (MAP) kinase activation, HNF-4 expression is
      downregulated in human hepatoma cells. This effect is mediated by the loss of
      CEBPalpha expression. During MAP kinase signaling, the recruitment of HNF-3beta
      and HNF-1alpha to the HNF-4 enhancer and RNA polymerase II to the proximal HNF-4
      promoter was compromised. CBP, Brg1, and TFIIB were also dissociated from the HNF
      4 regulatory regions, and the enhancer-promoter complex was disrupted.
      Interestingly, the extent of nucleosome acetylation did not decrease at either
      regulatory region, and HNF-6 and HNF-1alpha, as well as components of the TFIID,
      remained associated with the proximal promoter during the repressed state. The
      results point to an absolute requirement of enhancer-promoter communication for
      maintaining the active state of the HNF-4 gene and provide evidence for a
      molecular bookmarking mechanism, which may contribute to the prevention of
      permanent silencing of the locus during the repressed state.

PMID- 16980608
TI  - Functional analysis of p53 binding under differential stresses.
AB  - Hypoxia and DNA damage stabilize the p53 protein, but the subsequent effect that
      each stress has on transcriptional regulation of known p53 target genes is
      variable. We have used chromatin immunoprecipitation followed by CpG island (CGI)
      microarray hybridization to identify promoters bound by p53 under both DNA
      damaging and non-DNA-damaging conditions in HCT116 cells. Using gene-specific PCR
      analysis, we have verified an association with CGIs of the highest enrichment (>
      2.5-fold) (REV3L, XPMC2H, HNRPUL1, TOR1AIP1, glutathione peroxidase 1, and
      SCFD2), with CGIs of intermediate enrichment (> 2.2-fold) (COX7A2L, SYVN1, and
      JAG2), and with CGIs of low enrichment (> 2.0-fold) (MYC and PCNA). We found
      little difference in promoter binding when p53 is stabilized by these two
      distinctly different stresses. However, expression of these genes varies a great
      deal: while a few genes exhibit classical induction with adriamycin, the majority
      of the genes are unchanged or are mildly repressed by either hypoxia or
      adriamycin. Further analysis using p53 mutated in the core DNA binding domain
      revealed that the interaction of p53 with CGIs may be occurring through both
      sequence-dependent and -independent mechanisms. Taken together, these experiments
      describe the identification of novel p53 target genes and the subsequent
      discovery of distinctly different expression phenomena for p53 target genes under
      different stress scenarios.

PMID- 16980609
TI  - Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1
      and 2.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member
      of the TNF family that induces cancer cell death by apoptosis with some
      selectivity. TRAIL-induced apoptosis is mediated by the transmembrane receptors
      death receptor 4 (DR4) (also known as TRAIL-R1) and DR5 (TRAIL-R2). TRAIL can
      also bind decoy receptor 1 (DcR1) (TRAIL-R3) and DcR2 (TRAIL-R4) that fail to
      induce apoptosis since they lack and have a truncated cytoplasmic death domain,
      respectively. In addition, DcR1 and DcR2 inhibit DR4- and DR5-mediated, TRAIL
      induced apoptosis and we demonstrate here that this occurs through distinct
      mechanisms. While DcR1 prevents the assembly of the death-inducing signaling
      complex (DISC) by titrating TRAIL within lipid rafts, DcR2 is corecruited with
      DR5 within the DISC, where it inhibits initiator caspase activation. In addition,
      DcR2 prevents DR4 recruitment within the DR5 DISC. The specificity of DcR1- and
      DcR2-mediated TRAIL inhibition reveals an additional level of complexity for the
      regulation of TRAIL signaling.

PMID- 16980610
TI  - Distinct functions of dispersed GATA factor complexes at an endogenous gene
      locus.
AB  - The reciprocal expression of GATA-1 and GATA-2 during hematopoiesis is an
      important determinant of red blood cell development. Whereas Gata2 is
      preferentially transcribed early in hematopoiesis, elevated GATA-1 levels result
      in GATA-1 occupancy at sites upstream of the Gata2 locus and transcriptional
      repression. GATA-2 occupies these sites in the transcriptionally active locus,
      suggesting that a "GATA switch" abrogates GATA-2-mediated positive
      autoregulation. Chromatin immunoprecipitation (ChIP) coupled with genomic
      microarray analysis and quantitative ChIP analysis with GATA-1-null cells
      expressing an estrogen receptor ligand binding domain fusion to GATA-1 revealed
      additional GATA switches 77 kb upstream of Gata2 and within intron 4 at +9.5 kb.
      Despite indistinguishable GATA-1 occupancy at -77 kb and +9.5 kb versus other
      GATA switch sites, GATA-1 functioned uniquely at the different regions. GATA-1
      induced histone deacetylation at and near Gata2 but not at the -77 kb region. The
      -77 kb region, which was DNase I hypersensitive in both active and inactive
      states, conferred equivalent enhancer activities in GATA-1- and GATA-2-expressing
      cells. By contrast, the +9.5 kb region exhibited considerably stronger enhancer
      activity in GATA-2- than in GATA-1-expressing cells, and other GATA switch sites
      were active only in GATA-1- or GATA-2-expressing cells. Chromosome conformation
      capture analysis demonstrated higher-order interactions between the -77 kb region
      and Gata2 in the active and repressed states. These results indicate that
      dispersed GATA factor complexes function via long-range chromatin interactions
      and qualitatively distinct activities to regulate Gata2 transcription.

PMID- 16980611
TI  - Modulation of a P-TEFb functional equilibrium for the global control of cell
      growth and differentiation.
AB  - P-TEFb phosphorylates RNA polymerase II and negative elongation factors to
      stimulate general transcriptional elongation. It is kept in a functional
      equilibrium through alternately interacting with its positive (the Brd4 protein)
      and negative (the HEXIM1 protein and 7SK snRNA) regulators. To investigate the
      physiological significance of this phenomenon, we analyzed the responses of HeLa
      cells and murine erythroleukemia cells (MELC) to hexamethylene bisacetamide
      (HMBA), which inhibits growth and induces differentiation of many cell types. For
      both cell types, an efficient, albeit temporary disruption of the 7SK-HEXIM1-P
      TEFb snRNP and enhanced formation of the Brd4-P-TEFb complex occurred soon after
      the treatment started. When the P-TEFb-dependent HEXIM1 expression markedly
      increased as the treatment continued, the abundant HEXIM1 pushed the P-TEFb
      equilibrium back toward the 7SK/HEXIM1-bound state. For HeLa cells, as HMBA
      produced only a minor, temporary effect on their growth, the equilibrium
      gradually returned to its pretreatment level. In contrast, long-term treatment of
      MELC induced terminal division and differentiation. Concurrently, the P-TEFb
      equilibrium was shifted overwhelmingly toward the 7SK snRNP side. Together, these
      data link the P-TEFb equilibrium to the intracellular transcriptional demand and
      proliferative/differentiated states of cells.

PMID- 16980612
TI  - Zebra fish Dnmt1 and Suv39h1 regulate organ-specific terminal differentiation
      during development.
AB  - DNA methylation and histone methylation are two key epigenetic modifications that
      help govern heterochromatin dynamics. The roles for these chromatin-modifying
      activities in directing tissue-specific development remain largely unknown. To
      address this issue, we examined the roles of DNA methyltransferase 1 (Dnmt1) and
      the H3K9 histone methyltransferase Suv39h1 in zebra fish development. Knockdown
      of Dnmt1 in zebra fish embryos caused defects in terminal differentiation of the
      intestine, exocrine pancreas, and retina. Interestingly, not all tissues required
      Dnmt1, as differentiation of the liver and endocrine pancreas appeared normal.
      Proper differentiation depended on Dnmt1 catalytic activity, as Dnmt1 morphants
      could be rescued by active zebra fish or human DNMT1 but not by catalytically
      inactive derivatives. Dnmt1 morphants exhibited dramatic reductions of both
      genomic cytosine methylation and genome-wide H3K9 trimethyl levels, leading us to
      investigate the overlap of in vivo functions of Dnmt1 and Suv39h1. Embryos
      lacking Suv39h1 had organ-specific terminal differentiation defects that produced
      largely phenocopies of Dnmt1 morphants but retained wild-type levels of DNA
      methylation. Remarkably, suv39h1 overexpression rescued markers of terminal
      differentiation in Dnmt1 morphants. Our results suggest that Dnmt1 activity helps
      direct histone methylation by Suv39h1 and that, together, Dnmt1 and Suv39h1 help
      guide the terminal differentiation of particular tissues.

PMID- 16980613
TI  - New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and
      activity of class IIa histone deacetylases.
AB  - Class IIa histone deacetylases (HDACs) are found both in the cytoplasm and in the
      nucleus where they repress genes involved in several major developmental
      programs. In response to specific signals, the repressive activity of class IIa
      HDACs is neutralized through their phosphorylation on multiple N-terminal serine
      residues and 14-3-3-mediated nuclear exclusion. Here, we demonstrate that class
      IIa HDACs are subjected to signal-independent nuclear export that relies on their
      constitutive phosphorylation. We identify EMK and C-TAK1, two members of the
      microtubule affinity-regulating kinase (MARK)/Par-1 family, as regulators of this
      process. We further show that EMK and C-TAK1 phosphorylate class IIa HDACs on one
      of their multiple 14-3-3 binding sites and alter their subcellular localization
      and repressive function. Using HDAC7 as a paradigm, we extend these findings by
      demonstrating that signal-independent phosphorylation of the most N-terminal
      serine residue by the MARK/Par-1 kinases, i.e., Ser155, is a prerequisite for the
      phosphorylation of the nearby 14-3-3 site, Ser181. We propose that this multisite
      hierarchical phosphorylation by a variety of kinases allows for sophisticated
      regulation of class IIa HDACs function.

PMID- 16980614
TI  - Cortical migration defects in mice expressing A-RAF from the B-RAF locus.
AB  - We have previously shown that mice lacking the protein kinase B-RAF have defects
      in both neural and endothelial cell lineages and die around embryonic day 12
      (E12). To delineate the function of B-RAF in the brain, B-RAF KIN/KIN mice
      lacking B-RAF and expressing A-RAF under the control of the B-RAF locus were
      created. B-RAF KIN/KIN embryos displayed no vascular defects, no endothelial and
      neuronal apoptosis, or gross developmental abnormalities, and a significant
      proportion of these animals survived for up to 8 weeks. Cell proliferation in the
      neocortex was reduced from E14.5 onwards. Newborn cortical neurons were impaired
      in their migration toward the cortical plate, causing a depletion of Brn-2
      expressing pyramidal neurons in layers II, III, and V of the postnatal cortex.
      Our data reveal that B-RAF is an important mediator of neuronal survival,
      migration, and dendrite formation and that A-RAF cannot fully compensate for
      these functions.

PMID- 16980616
TI  - The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin
      activation through plasma membrane targeting of Rap1.
AB  - Adhesion of T cells after stimulation of the T-cell receptor (TCR) is mediated
      via signaling processes that have collectively been termed inside-out signaling.
      The molecular basis for inside-out signaling is not yet completely understood.
      Here, we show that a signaling module comprising the cytosolic adapter proteins
      ADAP and SKAP55 is involved in TCR-mediated inside-out signaling and, moreover,
      that the interaction between ADAP and SKAP55 is mandatory for integrin
      activation. Disruption of the ADAP/SKAP55 module leads to displacement of the
      small GTPase Rap1 from the plasma membrane without influencing its GTPase
      activity. These findings suggest that the ADAP/SKAP55 complex serves to recruit
      activated Rap1 to the plasma membrane. In line with this hypothesis is the
      finding that membrane targeting of the ADAP/SKAP55 module induces T-cell adhesion
      in the absence of TCR-mediated stimuli. However, it appears as if the ADAP/SKAP55
      module can exert its signaling function outside of the classical raft fraction of
      the cell membrane.

PMID- 16980615
TI  - DACH1 is a cell fate determination factor that inhibits cyclin D1 and breast
      tumor growth.
AB  - Obstacles to the expansion of cells with proliferative potential include the
      induction of cell death, telomere-based senescence, and the pRb and p53 tumor
      suppressors. Not infrequently, the molecular pathways regulating oncogenesis
      recapitulate aberrations of processes governing embryogenesis. The genetic
      network, consisting of the dachshund (dac), eyes absent (eya), eyeless, and sine
      oculis (so) genes, regulates cell fate determination in metazoans, with dac
      serving as a cointegrator through a So DNA-binding factor. Here, DACH1 inhibited
      oncogene-mediated breast oncogenesis, blocking breast cancer epithelial cell DNA
      synthesis, colony formation, growth in Matrigel, and tumor growth in mice.
      Genetic deletion studies demonstrated a requirement for cyclin D1 in DACH1
      mediated inhibition of DNA synthesis. DACH1 repressed cyclin D1 through a novel
      mechanism via a c-Jun DNA-binding partner, requiring the DACH1 alpha-helical DS
      domain which recruits corepressors to the local chromatin. Analysis of over 2,000
      patients demonstrated increased nuclear DACH1 expression correlated inversely
      with cellular mitosis and predicted improved breast cancer patient survival. The
      cell fate determination factor, DACH1, arrests breast tumor proliferation and
      growth in vivo providing a new mechanistic and potential therapeutic insight into
      this common disease.

PMID- 16980617
TI  - Characterization of R-ras3/m-ras null mice reveals a potential role in trophic
      factor signaling.
AB  - R-Ras3/M-Ras is a member of the RAS superfamily of small-molecular-weight GTP
      binding proteins. Previous studies have demonstrated high levels of expression in
      several regions of the central nervous system, and a constitutively active form
      of M-Ras promotes cytoskeletal reorganization, cellular transformation, survival,
      and differentiation. However, the physiological functions of M-Ras during
      embryogenesis and postnatal development have not been elucidated. By using a
      specific M-Ras antibody, we demonstrated a high level of M-Ras expression in
      astrocytes, in addition to neurons. Endogenous M-Ras was activated by several
      trophic factors in astrocytes, including epidermal growth factor (EGF), basic
      fibroblast growth factor, and hepatocyte growth factor. Interestingly, M-Ras
      activation by EGF was more sustained compared to prototypic Ras. A mouse strain
      deficient in M-Ras was generated to investigate its role in development. M-Ras
      null mice appeared phenotypically normal, and there was a lack of detectable
      morphological and neurological defects. In addition, primary astrocytes derived
      from Mras(-/-) mice did not appear to display substantial alterations in the
      activation of both the mitogen-activated protein kinase and phosphatidylinositol
      3-kinase pathways in response to trophic factors.

PMID- 16980618
TI  - Persistence of cooperatively stabilized signaling clusters drives T-cell
      activation.
AB  - Antigen recognition triggers the recruitment of the critical adaptor protein SLP
      76 to small macromolecular clusters nucleated by the T-cell receptor (TCR). These
      structures develop rapidly, in parallel with TCR-induced increases in tyrosine
      phosphorylation and cytosolic calcium, and are likely to contribute to TCR
      proximal signaling. Previously, we demonstrated that these SLP-76-containing
      clusters segregate from the TCR and move towards the center of the contact
      interface. Neither the function of these clusters nor the structural requirements
      governing their persistence have been examined extensively. Here we demonstrate
      that defects in cluster assembly and persistence are associated with defects in T
      cell activation in the absence of Lck, ZAP-70, or LAT. Clusters persist normally
      in the absence of phospholipase C-gamma1, indicating that in the absence of a
      critical effector, these structures are insufficient to drive T-cell activation.
      Furthermore, we show that the critical adaptors LAT and Gads localize with SLP-76
      in persistent clusters. Mutational analyses of LAT, Gads, and SLP-76 indicated
      that multiple domains within each of these proteins contribute to cluster
      persistence. These data indicate that multivalent cooperative interactions
      stabilize these persistent signaling clusters, which may correspond to the
      functional complexes predicted by kinetic proofreading models of T-cell
      activation.

PMID- 16980619
TI  - Hematopoietic precursor cells transiently reestablish permissiveness for X
      inactivation.
AB  - Xist is the trigger for X inactivation in female mammals. The long noncoding Xist
      RNA localizes along one of the two female X chromosomes and initiates chromosome
      wide silencing in the early embryo. In differentiated cells, Xist becomes
      dispensable for the maintenance of the inactive X, and its function for
      initiation of silencing is lost. How Xist mediates gene repression remains an
      open question. Here, we use an inducible Xist allele in adult mice to identify
      cells in which Xist can cause chromosome-wide silencing. We show that Xist has
      the ability to initiate silencing in immature hematopoietic precursor cells. In
      contrast, hematopoietic stem cells and mature blood cells are unable to initiate
      ectopic X inactivation. This indicates that pathways critical for silencing are
      transiently activated in hematopoietic differentiation. Xist-responsive cell
      types in normal female mice show a change of chromatin marks on the inactive X.
      However, dosage compensation is maintained throughout hematopoiesis. Therefore,
      Xist can initiate silencing in precursors with concomitant maintenance of dosage
      compensation. This suggests that Xist function is restricted in development by
      the limited activity of epigenetic pathways rather than by a change in the
      responsiveness of chromatin between embryonic and differentiated cell types.

PMID- 16980620
TI  - The essential gene wda encodes a WD40 repeat subunit of Drosophila SAGA required
      for histone H3 acetylation.
AB  - Histone acetylation provides a switch between transcriptionally repressive and
      permissive chromatin. By regulating the chromatin structure at specific
      promoters, histone acetyltransferases (HATs) carry out important functions during
      differentiation and development of higher eukaryotes. HAT complexes are present
      in organisms as diverse as Saccharomyces cerevisiae, humans, and flies. For
      example, the well-studied yeast SAGA is related to three mammalian complexes. We
      previously identified Drosophila melanogaster orthologues of yeast SAGA
      components Ada2, Ada3, Spt3, and Tra1 and demonstrated that they associate with
      dGcn5 in a high-molecular-weight complex. To better understand the function of
      Drosophila SAGA (dSAGA), we sought to affinity purify and characterize this
      complex in more detail. A proteomic approach led to the identification of an
      orthologue of the yeast protein Ada1 and the novel protein encoded by CG4448,
      referred to as WDA (will decrease acetylation). Embryos lacking both alleles of
      the wda gene exhibited reduced levels of histone H3 acetylation and could not
      develop into adult flies. Our results point to a critical function of dSAGA and
      histone acetylation during Drosophila development.

PMID- 16980621
TI  - Clustering of raft-associated proteins in the external membrane leaflet modulates
      internal leaflet H-ras diffusion and signaling.
AB  - One of the least-explored aspects of cholesterol-enriched domains (rafts) in
      cells is the coupling between such domains in the external and internal
      monolayers and its potential to modulate transbilayer signal transduction. Here,
      we employed fluorescence recovery after photobleaching to study the effects of
      antibody-mediated patching of influenza hemagglutinin (HA) proteins [raft
      resident wild-type HA and glycosylphosphatidylinositol-anchored HA, or the
      nonraft mutant HA(2A520)] on the lateral diffusion of internal-leaflet raft and
      nonraft Ras isoforms (H-Ras and K-Ras, respectively). Our studies demonstrate
      that the clustering of outer-leaflet or transmembrane raft-associated HA proteins
      (but not their nonraft mutants) retards the lateral diffusion of H-Ras (but not K
      Ras), suggesting stabilized interactions of H-Ras with the clusters of raft
      associated HA proteins. These modulations were paralleled by specific effects on
      the activity of H-Ras but not of the nonraft K-Ras. Thus, clustering raft
      associated HA proteins facilitated the early step whereby H-Ras is converted to
      an activated, GTP-loaded state but inhibited the ensuing step of downstream
      signaling via the Mek/Erk pathway. We propose a model for the modulation of
      transbilayer signaling by clustering of raft proteins, where external clustering
      (antibody or ligand mediated) enhances the association of internal-leaflet
      proteins with the stabilized clusters, promoting either enhancement or inhibition
      of signaling.

PMID- 16980622
TI  - Disruption of Ledgf/Psip1 results in perinatal mortality and homeotic skeletal
      transformations.
AB  - PC4- and SF2-interacting protein 1 (Psip1)-also known as lens epithelium-derived
      growth factor (Ledgf)-is a chromatin-associated protein that has been implicated
      in transcriptional regulation, mRNA splicing, and cell survival in vitro, but its
      biological function in vivo is unknown. We identified an embryonic stem cell
      clone with disrupted Psip1 in a gene trap screen. The resulting Psip1-betageo
      fusion protein retains chromatin-binding activity and the PWWP and AT hook
      domains of the wild-type protein but is missing the highly conserved C terminus.
      The majority of mice homozygous for the disrupted Psip1 gene died perinatally,
      but some survived to adulthood and displayed a range of phenotypic abnormalities,
      including low fertility, an absence of epididymal fat pads, and a tendency to
      develop blepharitis. However, contrary to expectations, the lens epithelium was
      normal. The mutant mice also exhibited motor and/or behavioral defects such as
      hind limb clenching, reduced grip strength, and reduced locomotor activity.
      Finally, both Psip1(-/-) neonates and surviving adults had craniofacial and
      skeletal abnormalities. They had brachycephaly, small rib cages, and homeotic
      skeletal transformations with incomplete penetrance. The latter phenotypes
      suggest a role for Psip1 in the control of Hox expression and may also explain
      why PSIP1 (LEDGF) is found as a fusion partner with NUP98 in myeloid leukemias.

PMID- 16980623
TI  - Intracellular role for sphingosine kinase 1 in intestinal adenoma cell
      proliferation.
AB  - Sphingosine kinase (Sphk) enzymes are important in intracellular sphingolipid
      metabolism as well as in the biosynthesis of sphingosine 1-phosphate (S1P), an
      extracellular lipid mediator. Here, we show that Sphk1 is expressed and is
      required for small intestinal tumor cell proliferation in Apc Min/+ mice. Adenoma
      size but not incidence was dramatically reduced in Apc Min/+ Sphk(-/-) mice.
      Concomitantly, epithelial cell proliferation in the polyps was significantly
      attenuated, suggesting that Sphk1 regulates adenoma progression. Although the S1P
      receptors (S1P1R, S1P2R, and S1P3R) are expressed, polyp incidence or size was
      unaltered in Apc Min/+ S1p2r(-/-), Apc Min/+ S1p3r(-/-), and Apc Min/+ S1p1r(+/-)
      bigenic mice. These data suggest that extracellular S1P signaling via its
      receptors is not involved in adenoma cell proliferation. Interestingly, tissue
      sphingosine content was elevated in the adenomas of Apc Min/+ Sphk1(-/-) mice,
      whereas S1P levels were not significantly altered. Concomitantly, epithelial cell
      proliferation and the expression of the G1/S cell cycle regulator CDK4 and c-myc
      were diminished in the polyps of Apc Min/+ Sphk1(-/-) mice. In rat intestinal
      epithelial (RIE) cells in vitro, Sphk1 overexpression enhanced cell cycle
      traverse at the G1/S boundary. In addition, RIE cells treated with sphingosine
      but not C6-ceramide exhibited reduced cell proliferation, reduced retinoblastoma
      protein phosphorylation, and cyclin-dependent kinase 4 (Cdk4) expression. Our
      findings suggest that Sphk1 plays a critical role in intestinal tumor cell
      proliferation and that inhibitors of Sphk1 may be useful in the control of
      intestinal cancer.

PMID- 16980624
TI  - Control of the DNA methylation system component MBD2 by protein arginine
      methylation.
AB  - DNA methylation is vital for proper chromatin structure and function in mammalian
      cells. Genetic removal of the enzymes that catalyze DNA methylation results in
      defective imprinting, transposon silencing, X chromosome dosage compensation, and
      genome stability. This epigenetic modification is interpreted by methyl-DNA
      binding domain (MBD) proteins. MBD proteins respond to methylated DNA by
      recruiting histone deacetylases (HDAC) and other transcription repression factors
      to the chromatin. The MBD2 protein is dispensable for animal viability, but it is
      implicated in the genesis of colon tumors. Here we report that the MBD2 protein
      is controlled by arginine methylation. We identify the protein arginine
      methyltransferase enzymes that catalyze this modification and show that arginine
      methylation inhibits the function of MBD2. Arginine methylation of MBD2 reduces
      MBD2-methyl-DNA complex formation, reduces MBD2-HDAC repression complex
      formation, and impairs the transcription repression function of MBD2 in cells.
      Our report provides a molecular description of a potential regulatory mechanism
      for an MBD protein family member. It is the first to demonstrate that protein
      arginine methyltransferases participate in the DNA methylation system of
      chromatin control.

PMID- 16980625
TI  - Hyporesponsiveness to glucocorticoids in mice genetically deficient for the
      corticosteroid binding globulin.
AB  - Corticosteroid binding globulin (CBG) is the carrier for glucocorticoids in
      plasma. The protein is believed to keep the steroids inactive and to regulate the
      amount of free hormone acting on target tissues (free hormone hypothesis). Here,
      we generated a mouse model genetically deficient for CBG to test the contribution
      of the carrier to glucocorticoid action and adrenocortical stress response. The
      absence of CBG resulted in a lack of corticosterone binding activity in serum and
      in an approximately 10-fold increase in free corticosterone levels in CBG-null
      mice, consistent with its role in regulation of circulating free hormone levels.
      Surprisingly, cbg(-/-) animals did not exhibit features seen in organisms with
      enhanced glucocorticoid signaling. Rather, the mice exhibited increased activity
      of the pituitary axis of hormonal control, normal levels of gluconeogenetic
      enzymes, and fatigue, as well as an aggravated response to septic shock,
      indicating an inability to appropriately respond to the excess free
      corticosterone in the absence of CBG. Thus, our data suggest an active role for
      CBG in bioavailability, local delivery, and/or cellular signal transduction of
      glucocorticoids that extends beyond a function as a mere cargo transporter.

PMID- 16980626
TI  - Transcriptional repressor foxl1 regulates central nervous system development by
      suppressing shh expression in zebra fish.
AB  - We identified zebra fish forkhead transcription factor l1 (zfoxl1) as a gene
      strongly expressed in neural tissues such as midbrain, hindbrain, and the otic
      vesicle at the early embryonic stage. Loss of the function of zfoxl1 effected by
      morpholino antisense oligonucleotide resulted in defects in midbrain and eye
      development, and in that of formation of the pectoral fins. Interestingly,
      ectopic expression of shh in the midbrain and elevated pax2a expression in the
      optic stalk were observed in foxl1 MO-injected embryos. In contrast, expression
      of pax6a, which is negatively regulated by shh, was suppressed in the thalamus
      and pretectum regions, supporting the idea of augmentation of the shh signaling
      pathway by suppression of foxl1. Expression of zfoxl1-EnR (repressing) rather
      than zfoxl1-VP16 (activating) resulted in a phenotype similar to that induced by
      foxl1-mRNA, suggesting that foxl1 may act as a transcriptional repressor of shh
      in zebra fish embryos. Supporting this notion, foxl1 suppressed isolated 2.7-kb
      shh promoter activity in PC12 cells, and the minimal region of foxl1 required for
      its transcriptional repressor activity showed strong homology with the groucho
      binding motif, which is found in genes encoding various homeodomain proteins. In
      view of all of our data taken together, we propose zfoxl1 to be a novel regulator
      of neural development that acts by suppressing shh expression.

PMID- 16980627
TI  - DRONC coordinates cell death and compensatory proliferation.
AB  - Accidental cell death often leads to compensatory proliferation. In Drosophila
      imaginal discs, for example, gamma-irradiation induces extensive cell death,
      which is rapidly compensated by elevated proliferation. Excessive compensatory
      proliferation can be artificially induced by "undead cells" that are kept alive
      by inhibition of effector caspases in the presence of apoptotic stimuli. This
      suggests that compensatory proliferation is induced by dying cells as part of the
      apoptosis program. Here, we provide genetic evidence that the Drosophila
      initiator caspase DRONC governs both apoptosis execution and subsequent
      compensatory proliferation. We examined mutants of five Drosophila caspases and
      identified the initiator caspase DRONC and the effector caspase DRICE as crucial
      executioners of apoptosis. Artificial compensatory proliferation induced by
      coexpression of Reaper and p35 was completely suppressed in dronc mutants.
      Moreover, compensatory proliferation after gamma-irradiation was enhanced in
      drice mutants, in which DRONC is activated but the cells remain alive. These
      results show that the apoptotic pathway bifurcates at DRONC and that DRONC
      coordinates the execution of cell death and compensatory proliferation.

PMID- 16980628
TI  - MDM2 promotes cell motility and invasiveness by regulating E-cadherin
      degradation.
AB  - Gene amplification and protein overexpression of MDM2, which is often found in
      certain types of cancers, indicate that MDM2 plays an important role in
      tumorigenesis. Interestingly, several clinical reports have demonstrated that
      amplification of the MDM2 gene correlates with the metastatic stage. Using an
      antibody array assay, we identified E-cadherin as an MDM2-binding protein and
      confirmed that E-cadherin is a substrate for the MDM2 E3 ubiquitin ligase. We
      demonstrate that MDM2 interacts in vivo with E-cadherin, resulting in its
      ubiquitination and degradation. This regulation appears to be clinically
      relevant, as we found a significant correlation between high MDM2 and low E
      cadherin protein levels in resected tumor specimens recovered from breast cancer
      patients with lymph node metastases. Ectopic expression of MDM2 in breast cancer
      cells was found to disrupt cell-cell contacts and enhance cell motility and
      invasive potential. We found that E-cadherin and MDM2 colocalized on the plasma
      membrane and in the early endosome, where ubiquitin moieties were attached to E
      cadherin. Blocking endocytosis with dominant-negative mutants of dynamin
      abolished the association of MDM2 with E-cadherin, prevented E-cadherin
      degradation, and attenuated cell motility as observed by fluorescence microscopy.
      Thus, we provide evidence to support a novel role for MDM2 in regulating cell
      adhesions by a mechanism that involves degrading and down-regulating the
      expression of E-cadherin via an endosome pathway. This novel MDM2-regulated
      pathway is likely to play a biologically relevant role in cancer metastasis.

PMID- 16980629
TI  - NF-kappaB/Rel regulates inhibitory and excitatory neuronal function and synaptic
      plasticity.
AB  - Changes in synaptic plasticity required for memory formation are dynamically
      regulated through opposing excitatory and inhibitory neurotransmissions. To
      explore the potential contribution of NF-kappaB/Rel to these processes, we
      generated transgenic mice conditionally expressing a potent NF-kappaB/Rel
      inhibitor termed IkappaBalpha superrepressor (IkappaBalpha-SR). Using the prion
      promoter-enhancer, IkappaBalpha-SR is robustly expressed in inhibitory GABAergic
      interneurons and, at lower levels, in excitatory neurons but not in glia. This
      neuronal pattern of IkappaBalpha-SR expression leads to decreased expression of
      glutamate decarboxylase 65 (GAD65), the enzyme required for synthesis of the
      major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) in GABAergic
      interneurons. IkappaBalpha-SR expression also results in diminished basal GluR1
      levels and impaired synaptic strength (input/output function), both of which are
      fully restored following activity-based task learning. Consistent with diminished
      GAD65-derived inhibitory tone and enhanced excitatory firing, IkappaBalpha-SR+
      mice exhibit increased late-phase long-term potentiation, hyperactivity,
      seizures, increased exploratory activity, and enhanced spatial learning and
      memory. IkappaBalpha-SR+ neurons also express higher levels of the activity
      regulated, cytoskeleton-associated (Arc) protein, consistent with neuronal
      hyperexcitability. These findings suggest that NF-kappaB/Rel transcription
      factors act as pivotal regulators of activity-dependent inhibitory and excitatory
      neuronal function regulating synaptic plasticity and memory.

PMID- 16980630
TI  - Bioinformatic and comparative localization of Rab proteins reveals functional
      insights into the uncharacterized GTPases Ypt10p and Ypt11p.
AB  - A striking characteristic of a Rab protein is its steady-state localization to
      the cytosolic surface of a particular subcellular membrane. In this study, we
      have undertaken a combined bioinformatic and experimental approach to examine the
      evolutionary conservation of Rab protein localization. A comprehensive primary
      sequence classification shows that 10 out of the 11 Rab proteins identified in
      the yeast (Saccharomyces cerevisiae) genome can be grouped within a major
      subclass, each comprising multiple Rab orthologs from diverse species. We
      compared the locations of individual yeast Rab proteins with their localizations
      following ectopic expression in mammalian cells. Our results suggest that green
      fluorescent protein-tagged Rab proteins maintain localizations across large
      evolutionary distances and that the major known player in the Rab localization
      pathway, mammalian Rab-GDI, is able to function in yeast. These findings enable
      us to provide insight into novel gene functions and classify the uncharacterized
      Rab proteins Ypt10p (YBR264C) as being involved in endocytic function and Ypt11p
      (YNL304W) as being localized to the endoplasmic reticulum, where we demonstrate
      it is required for organelle inheritance.

PMID- 16980631
TI  - BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1
      heterodimer.
AB  - CLOCK and BMAL1 are bHLH-PAS-containing transcription factors that bind to E-box
      elements and are indispensable for expression of core circadian clock components
      such as the Per and Cry genes. A key step in expression is the heterodimerization
      of CLOCK and BMAL1 and their accumulation in the nucleus with an approximately 24
      h periodicity. We show here that nucleocytoplasmic shuttling of BMAL1 is
      essential for transactivation and for degradation of the CLOCK/BMAL1 heterodimer.
      Using serial deletions and point mutants, we identified a functional nuclear
      localization signal and Crm1-dependent nuclear export signals in BMAL1. Transient
      transfection experiments revealed that heterodimerization of CLOCK and BMAL1
      accelerates their turnover, as well as E-box-dependent clock gene transcription.
      Moreover, in embryonic mouse fibroblasts, robust transcription of Per2 is tightly
      associated with massive degradation of the CLOCK/BMAL1 heterodimer. CRY proteins
      suppressed this process during the transcription-negative phase and led to
      nuclear accumulation of the CLOCK/BMAL1 heterodimer. Thus, these findings suggest
      that the decrease of BMAL1 abundance during the circadian cycle reflects robust
      transcriptional activation of clock genes rather than inhibition of BMAL1
      synthesis.

PMID- 16980633
TI  - The cumulative effect of rural and regional residence on the health of older
      adults.
AB  - OBJECTIVE: This study considers whether rural status or living in a particular
      region of the United States has effects on mental and physical health. The
      analyses examine whether there are independent and interactive effects of rural
      status and region of residence on health, beyond individual level factors related
      to poverty. METHODS: Ordinary least squares (OLS) regression models are used to
      examine the relationships between rural and regional residence and health across
      three time periods. RESULTS: Negative health effects of rural residence were
      found only in the South region. Positive health effects of rural residence were
      found only in the Midwest region. There are no observed health risks associated
      with rural or regional residence across group. DISCUSSION: The results indicate a
      cumulative risk of rural and Southern residence for older men and women. Living
      in a rural place in the midwestern United States seems to provide unique sources
      of health benefits.

PMID- 16980634
TI  - Development of a screening tool for identifying elderly people at risk of abuse
      by their caregivers.
AB  - OBJECTIVE: This study developed and assessed an instrument to identify older
      people at high risk of abuse based on Reis and Nahmiash's Indicators of Abuse
      (IOA) screen. METHOD: A total of 108 people 65 and older, hospitalized in
      internal medicine departments at two major hospitals in Israel, were screened
      together with their principal caregivers. The interview was based on the expanded
      IOA (E-IOA) and a list of evident signs of abuse. RESULTS: Reliability and
      validity of the E-IOA were tested and confirmed. Indicators proved to be a
      significant predictor of evident signs of abuse. The E-IOA correctly discerned
      92.7% of those at high risk for abuse and 97.9% of those who did not suffer
      abuse. The main indicators for risk were behavioral problems, emotional problems,
      and family problems of the caregiver and the elderly person. Fourteen (13%)
      experienced abuse. DISCUSSION: The proposed assessment tool can be an
      instrumental guide to identify elderly people who suffer abuse (unidentified) or
      who are at high risk.

PMID- 16980632
TI  - Locus-wide chromatin remodeling and enhanced androgen receptor-mediated
      transcription in recurrent prostate tumor cells.
AB  - Prostate cancers (PCas) become resistant to hormone withdrawal through increased
      androgen receptor (AR) signaling. Here we show increased AR-mediated
      transcription efficiency in PCa cells that have acquired the ability to grow in
      low concentrations of androgen. Compared to androgen-dependent PCa cells, these
      cells showed increased activity of transiently transfected reporters and
      increased mRNA synthesis relative to levels of AR occupancy of the prostate
      specific antigen (PSA) gene. The locus also displayed up to 10-fold-higher levels
      of histone H3-K9/K14 acetylation and H3-K4 methylation across the entire body of
      the gene. Although similar increased mRNA expression and locus-wide histone
      acetylation were also observed at another kallikrein locus (KLK2), at a third AR
      target locus (TMPRSS2) increased gene expression and locus-wide histone
      acetylation were not seen in the absence of ligand. Androgen-independent PCa
      cells have thus evolved three distinctive alterations in AR-mediated
      transcription. First, increased RNA polymerase initiation and processivity
      contributed to increased gene expression. Second, AR signaling was more sensitive
      to ligand. Third, locus-wide chromatin remodeling conducive to the increased gene
      expression in the absence of ligand was apparent and depended on sustained AR
      activity. Therefore, increased AR ligand sensitivity as well as locus-specific
      chromatin alterations contribute to basal gene expression of a subpopulation of
      specific AR target genes in androgen-independent PCa cells. These features
      contribute to the androgen-independent phenotype of these cells.

PMID- 16980635
TI  - Elderly veterans' beliefs concerning life-sustaining treatment and the control of
      their end-of-life health and health care.
AB  - OBJECTIVE: This study used qualitative methods to explore patients' beliefs about
      control of their end-of-life health and health care. METHOD: The authors
      recruited 30 elderly patients from a large, urban Veterans Administration medical
      center in the United States and engaged them in semistructured interviews about
      end-of-life care concepts. Using grounded theory methods, they coded,
      categorized, and compared responses. RESULTS: The authors discovered that
      patients' decisions about using life sustaining treatment were interconnected
      with their beliefs about their degree of control over circumstances and the role
      of external factors, including a higher power; institutions and individuals;
      medical interventions; medical conditions; and luck, chance, or fate. DISCUSSION:
      The results shed light on why patients do or do not take active roles in advance
      decisions concerning the use of life-sustaining treatment.

PMID- 16980636
TI  - Comparison of data quality for reports and ratings of ambulatory care by African
      American and White Medicare managed care enrollees.
AB  - OBJECTIVE: Compare missing data and reliability of health care evaluations
      between African Americans and Whites in Medicare managed care health plans.
      METHOD: Consumer Assessment of Healthcare Providers and Systems (CAHPS) 3.0
      health plan survey data collected from 109,980 Medicare managed care enrollees
      (101,189 Whites, 8,791 African Americans) in 321 plans. Participants self
      administered the survey and four single-item global ratings of care. RESULTS:
      Missing data rates were significantly higher for African Americans than Whites on
      all CAHPS items (p < .0001). Internal consistency reliability estimates for the
      CAHPS scales did not differ significantly between African Americans and Whites,
      but plan-level reliability estimates for the scales and global rating items were
      significantly lower for African Americans than Whites. DISCUSSION: Higher missing
      data rates and lower plan-level reliability estimates for African American
      Medicare managed care enrollees suggest caution in making race/ethnicity
      comparisons. Future efforts are needed to enhance the quality of data collected
      from older African Americans.

PMID- 16980637
TI  - Predictors of self-assessed health, anxiety, and depressive symptoms in nursing
      home residents at week 1 postrelocation.
AB  - OBJECTIVE: The purpose of this study was to determine if person factors,
      situation factors, and cognitive appraisal predict health outcomes during the
      first week postrelocation in older adults relocating to a nursing home. METHOD:
      Data were collected using face-to-face interviews with a convenience sample of
      114 older adults. The study was guided by Lazarus and Folkman's stress-appraisal
      coping framework. RESULTS: Hierarchical regression analyses accounted for 12% of
      the variance in self assessed health, 48% of the variance in anxiety, and 55% of
      the variance in depressive symptoms. For all three health outcomes, at least one
      type of cognitive appraisal provided additional explanation of the dependent
      variable beyond that of the person and situation factors. DISCUSSION: The
      findings provide additional empirical evidence for Lazarus and Folkman's stress
      appraisal-coping framework. Findings from this study emphasized the importance of
      mastery, social support, and cognitive appraisal of the older adult relocating
      successfully to a nursing home.

PMID- 16980638
TI  - The role of pain in the recovery of instrumental and social functioning after hip
      fracture.
AB  - OBJECTIVE: It is critical to identify modifiable factors associated with
      functional recovery from hip fracture. The authors examined the association
      between pain intensity and two functional endpoints-instrumental activities of
      daily living and social activity participation-after hip fracture. METHOD: A
      total of 270 cognitively intact, community-dwelling persons older than 65 who
      underwent surgical hip fracture repair in New Haven, Connecticut, were followed
      for 12 months. RESULTS: Pain intensity was strongly negatively associated with
      both instrumental and social functioning (p values < .001). Increases in pain
      intensity between 6 and 12 months were also associated with concurrent decreases
      in function (p values < .001). These relationships were partly explained by
      depressive symptoms and a marker of physical ability-gait speed. DISCUSSION:
      Interventions to control pain may enhance functional status after hip fracture;
      however, pain relief must be maintained to sustain recovery. Attention to the
      complex relationships among pain, depressive symptoms, and physical impairments
      should inform intervention development.

PMID- 16980639
TI  - Moraxella, down but not out--the eye bug that won't go away.

PMID- 16980640
TI  - Relationship between macular hole size and the potential benefit of internal
      limiting membrane peeling.

PMID- 16980641
TI  - Some ethical considerations for the "off-label" use of drugs such as Avastin.

PMID- 16980642
TI  - Disability, sight impairment, and the law.

PMID- 16980643
TI  - The first successful full-thickness corneal transplant: a commentary on Eduard
      Zirm's landmark paper of 1906.

PMID- 16980644
TI  - Influence of cataract on optical coherence tomography image quality and retinal
      thickness.
AB  - BACKGROUND: As optical coherence tomography (OCT) is widely used for diagnosis
      and monitoring of ocular pathology, especially in the elderly people, the
      influence of cataract on image quality and macular retinal thickness was studied.
      METHODS: In 29 patients scheduled for cataract surgery, preoperative and
      postoperative OCT scans were obtained. Cataracts were categorised as nuclear,
      posterior or cortical. Parameters for image quality (signal-to-noise ratio (SNR))
      and signal strength and macular thickness were compared. A three-level expert
      grading scale was used to evaluate the discriminative abilities of SNR and signal
      strength. RESULTS: Nuclear cataracts (n = 12) provided better preoperative scans
      (higher SNR/signal strength) than posterior (n = 7) and cortical (n = 10)
      cataracts (p<0.004). Postoperatively SNR and signal strength increased
      significantly in all patients (p<0.001). The SNR was better at discriminating
      poor from acceptable and good scans than signal strength (area under the receiver
      operating curve: 0.879 and 0.810, respectively). Postoperative macular thickness
      overall showed a significant increase (p = 0.005), most evident in patients with
      posterior cataracts (p = 0.028). CONCLUSIONS: OCT imaging is influenced by
      cataract; image quality is reduced preoperatively and macular thickness
      measurements are slightly increased postoperatively. In individual patients, OCT
      scans remain reliable for gross clinical interpretation, even in the presence of
      cataract.

PMID- 16980645
TI  - Metachronous ispilateral conjunctival then choroidal melanoma.

PMID- 16980646
TI  - Combination photodynamic therapy and juxtascleral triamcinolone acetonide for the
      treatment of a peripapillary choroidal neovascular membrane associated with
      papilloedema.

PMID- 16980647
TI  - Advanced bilateral persistent fetal vasculature associated with a novel mutation
      in the Norrie gene.

PMID- 16980648
TI  - Isolated lichen planus of the conjunctiva.

PMID- 16980649
TI  - Bilateral peripapillary staphyloma, a clinicoradiological report.

PMID- 16980650
TI  - Recurrent hypopyon in chronic anterior uveitis of pauciarticular juvenile
      idiopathic arthritis.

PMID- 16980651
TI  - In vivo measurement of opacified H60M intraocular lenses using Scheimpflug
      photography.

PMID- 16980652
TI  - A simple model for teaching indirect ophthalmoscopy.

PMID- 16980653
TI  - Neodymium:YAG laser treatment for a premacular haemorrhage in a T cell
      lymphoblastic lymphoma patient.

PMID- 16980654
TI  - Predicting steroid response in muscle disease.

PMID- 16980655
TI  - Respiratory involvement in inherited primary muscle conditions.
AB  - Patients with inherited muscle disorders can develop respiratory muscle weakness
      leading to ventilatory failure. Predicting the extent of respiratory involvement
      in the different types of inherited muscle disorders is important, as it allows
      clinicians to impart prognostic information and offers an opportunity for early
      interventional management strategies. The approach to respiratory assessment in
      patients with muscle disorders, the current knowledge of respiratory impairment
      in different muscle disorders and advice on the management of respiratory
      complications are summarised.

PMID- 16980656
TI  - The glucocorticoid receptor N363S polymorphism and steroid response in Duchenne
      dystrophy.
AB  - BACKGROUND: Steroid administration is beneficial in Duchenne muscular dystrophy
      (DMD), but the response, incidence, and the severity of side effects are
      variable. AIMS: To investigate whether glucocorticoid receptor (GRL) gene
      polymorphisms may be responsible for glucocorticoid sensitivity in DMD. METHODS:
      Forty eight DMD patients treated either with prednisone or deflazacort were
      subjected to genetic analyses of the GRL gene. RESULTS: Mutation studies revealed
      an heterozygous A to G mutation at GRL cDNA position 1220 in three DMD patients
      resulting in an asparagine to serine amino acid change at amino acid position 363
      (N363S). The N363S carrier DMD patients showed a trend towards a later age at
      loss of ambulation in comparison with non-carrier patients. CONCLUSIONS: These
      data suggest that the N363S GRL polymorphism may be implicated in the long term
      response to glucocorticoids.

PMID- 16980657
TI  - Neurological picture. Recurrent episodes of sudden tetraplegia caused by an
      anterior cervical arachnoid cyst.

PMID- 16980658
TI  - Expression of granulysin in polymyositis and inclusion-body myositis.
AB  - BACKGROUND: Granulysin, a recently defined cytolytic molecule, is expressed in
      cytotoxic T cells and natural killer cells in a similar way to perforin, which is
      reported to have a major role in the pathogenesis of polymyositis and inclusion
      body myositis (IBM). OBJECTIVE: To clarify the role of granulysin in polymyositis
      and IBM. METHODS: The expression of granulysin and perforin was examined by
      double staining with CD8, CD4 and CD56 in endomysial infiltrating cells and
      autoinvasive cells in muscle biopsy specimens of 17 patients with polymyositis (6
      steroid resistant and 11 steroid responsive) and of 7 patients with IBM. RESULTS:
      Similar to perforin, granulysin was expressed in CD8, CD4 or CD56 cells in
      patients with polymyositis and IBM. The ratio of cells double positive for
      granulysin and CD8 to all CD8 cells at endomysial sites was notably higher in
      steroid-resistant polymyositis than in steroid-responsive polymyositis and IBM.
      CONCLUSION: Granulysin expression in CD8 cells seems to be correlated with
      steroid resistance in polymyositis.

PMID- 16980659
TI  - Mirror movements in Parkinson's disease: effect of dopaminergic drugs.

PMID- 16980660
TI  - Severe amnesia after a restricted lesion in the left hippocampal body.

PMID- 16980661
TI  - Opercular syndrome due to non-convulsive status epilepticus in an adult.

PMID- 16980662
TI  - Successful immunosuppressive treatment and long-term follow-up of anti-Ri
      associated paraneoplastic myelitis.

PMID- 16980663
TI  - Hydatid cysts in breast: mammography and ultrasound findings.
AB  - A case of a 48-year-old woman with hydatid disease of the breast is presented.
      The ultrasound and mammogram findings are shown and an uncommon ultrasound
      appearance of hydatid cyst in the breast is discussed.

PMID- 16980664
TI  - A rare case of extranodal Rosai-Dorfman disease.
AB  - Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder which
      commonly affects the lymph nodes. Extranodal involvement along with concomitant
      nodal disease occurs in about 43% of cases. Isolated extranodal Rosai-Dorfman
      disease is relatively uncommon. We report this rare case of isolated extranodal
      Rosai-Dorfman disease and its ultrasound findings.

PMID- 16980665
TI  - Primary extragonadal retroperitoneal teratoma in an adult.
AB  - Primary retroperitoneal teratoma is a rare entity in adults. It has a distinctive
      imaging appearance. We describe a case of a 22-year-old patient who was referred
      to our hospital with the complaint of abdominal distension. Radiological work-up
      disclosed a retroperitoneal teratoma. Laparotomy with tumour resection was
      performed. Pathological examination revealed a benign cystic teratoma. The
      patient is doing well at follow-up.

PMID- 16980666
TI  - A case of syringomyelia associated with cervical spondylosis.
AB  - Cervical spondylosis is an extremely common condition causing spinal cord
      compression, and yet it very rarely causes secondary syrinx formation. We report
      a case of cervical spondylosis with associated syringomyelia and review the
      possible pathogenesis of this condition.

PMID- 16980667
TI  - MRI appearance of primary giant ovarian leiomyoma in a hysterectomised woman.
AB  - Primary leiomyoma is a rare, benign tumour of the ovary. We describe the MRI
      features of an ovarian leiomyoma identified in a 51-year-old woman after
      hysterectomy. The tumour appeared as a well-circumscribed low signal intensity
      mass on T(1) weighted imaging, with mixed signal intensity on T2 weighted
      imaging. Areas of high signal intensity on T2 weighted imaging corresponded to
      degeneration of leiomyoma. Dynamic contrast-enhanced imaging revealed early
      enhancement of the lesion. MRI appearance was thus similar to that of uterine
      leiomyoma. This case suggests the potential usefulness of dynamic contrast
      enhanced MRI for the diagnosis of ovarian leiomyoma.

PMID- 16980668
TI  - Symptomatic accessory soleus muscle: diagnosis and follow-up on magnetic
      resonance imaging.
AB  - The accessory soleus muscle is a rare anatomical variant which, although
      congenital in origin, may manifest in the second and third decades of life as a
      painful ankle mass or an asymptomatic ankle soft tissue swelling. We report a
      symptomatic accessory soleus muscle in a 21-year-old male soldier that was
      diagnosed and followed-up on MRI. Initial MRI showed a mass with signal
      characteristics of normal muscle, but in an abnormal location. There was
      increased intrafascial fluid and perimuscular oedema around the accessory soleus
      muscle. Following conservative treatment, repeat MRI showed resolution of this
      intrafascial fluid collection and perimuscular oedema, concurrent with relief of
      the patient's painful symptoms.

PMID- 16980669
TI  - Giant coronary artery aneurysm secondary to Kawasaki disease: diagnosis in an
      adult by multi-detector row CT coronary angiography.
AB  - We present the case of an adult female patient with a giant coronary artery
      aneurysm secondary to Kawasaki disease diagnosed for the first time, as far as
      the authors are aware, on multi-detector row computed tomography (MDCT). The long
      term complications relate to the persistence of these aneurysms with giant
      coronary aneurysms having the lowest regression rate, the highest risk of
      stenosis and strongest association with myocardial infarction. MDCT coronary
      angiography represents an ideal, alternative non-invasive imaging modality for
      the diagnosis and follow-up of the coronary arterial complications of Kawasaki
      disease, thereby avoiding invasive coronary imaging, and its use in the
      management algorithm should be considered. We also aim to contribute to the
      expanding clinical role of MDCT coronary imaging.

PMID- 16980670
TI  - Unusual appearance of retroperitoneal fibrosis simulating a tumour.
AB  - Retroperitoneal fibrosis (RPF) is an uncommon entity that usually presents as a
      fibrous plaque-like lesion that encases the aorta and inferior vena cava below
      the level of the renal arteries. We present an unusual mass-like appearance of
      this disease simulating a tumour, with foci of calcification, seen in a young
      girl.

PMID- 16980671
TI  - Spontaneous thrombosis of congenital cerebral arteriovenous malformation
      complicated by subdural collection: in utero detection with disappearance in
      infancy.
AB  - We report a case of congenital left temporal lobe arteriovenous malformation
      (AVM) detected by cranial ultrasound in utero and confirmed immediately after
      birth by cranial Doppler ultrasound and cranial MRI. The AVM disappeared on
      follow-up cranial MRI 4 months later. A small left frontal subdural collection
      was present on these follow-up MR images, which subsequently resolved by the 7
      month MRI study. The cause of the spontaneous thrombosis of the AVM is uncertain.
      The frontal subdural collection may be secondary to volume loss. This case
      documents the perinatal presence of AVM. The baby was neurologically intact
      before, during and after the thrombosis of the AVM.

PMID- 16980672
TI  - CT findings of malarial spleen.
AB  - Malaria is one of the most frequent causes of fever among travellers to tropical
      countries. We report the CT imaging findings of poor contrast enhancement of the
      spleen on arterial phase in a case of malaria presenting as splenomegaly. To the
      best of our knowledge, this is the first report of malarial spleen diagnosed by
      these CT results.

PMID- 16980673
TI  - Huge renal lipoma with prominent hypervascular non-adipose elements.
AB  - A primary renal lipoma is a very rare neoplasm of the kidney and only 20 cases
      have been reported in the literature. We report a case of a huge retroperitoneal
      mass that presented as a hypervascular tumour with a prominent fat component,
      mimicking an angiomyolipoma or a liposarcoma in imaging studies. This finding
      presented a diagnostic challenge in terms of selecting medical versus surgical
      intervention. Surgical excision of the lesions was performed and the pathological
      evaluation revealed a renal lipoma with extrarenal growth.

PMID- 16980674
TI  - Double retroaortic left renal veins as a possible cause of pelvic congestion
      syndrome: imaging findings in two patients.
AB  - Pelvic congestion syndrome is characterized by chronic pelvic pain and varicose
      veins around the uterus and ovaries. We report two cases of double retroaortic
      left renal vein, associated with left-sided pelvic congestion syndrome, diagnosed
      by CT and confirmed by clinical findings and colour Doppler ultrasound. Double
      retroaortic left renal veins may be a contributing factor for the development of
      left pelvic congestion syndrome. This is the first report of double retroaortic
      left renal vein and associated pelvic congestion syndrome.

PMID- 16980675
TI  - Multiple hyperechoic testicular lesions are a common finding on ultrasound in
      Cowden disease and represent lipomatosis of the testis.
AB  - Cowden disease (CD) is a genetic disease associated with multiple hamartomas and
      malignant neoplasms. During investigations for possible subnormal fertility, a
      series of eight males with CD underwent ultrasound scanning of their testes. Our
      findings detail the seven adult patients that were found to have multiple and
      bilateral testicular lesions on ultrasound. These lesions in Cowden's patients
      represent a newly described testicular pathology - lipomatosis of the testis.
      Here we detail the radiological findings. Ultrasound findings showed multiple
      (estimated 40+) discreet lesions randomly scattered thoughout the parenchyma of
      each affected testis. The lesions themselves had heterogeneous echo texture, but
      all being hyperechoic and with a variable size from 1 mm to 6 mm. One patient
      underwent MR examination of the lesions in which a high T(1) signal was seen, but
      no useful characteristic features were identifiable.

PMID- 16980676
TI  - Accuracy and precision of an external-marker tracking-system for radiotherapy
      treatments.
AB  - The purpose of this work was to determine the accuracy and precision of a real
      time motion-tracking system (Osiris+) for the monitoring of external markers used
      on patients receiving radiotherapy treatments. Random and systematic errors in
      the system were evaluated for linear (1D), circular (2D) and elliptical (3D)
      continuous motions, and for a set of static positions offset from an origin. A
      Wellhofer beam data measurement system and a computer controlled platform (which
      could be programmed to give motion in 3D) were used to move a hemi-spherical test
      object. The test object had four markers of the type used on patients. Three
      markers were aligned in the central plane and a fourth was positioned out of
      plane. Errors were expressed as deviations from the planned positions at the
      sampled time points. The marked points on the test object were tracked for the
      linear motion case with a variation from the true position of less than +/-1 mm,
      except for two extreme situations. The variation was within +/-2 mm when the
      lights were dimmed and when the amplitude of the movement was +/-5.0 cm. The 2D
      circular motion was tracked with a standard deviation of 1 mm or less over four
      cycles. The sampling rates of the system were found to be 0.3-0.4 s when it was
      monitoring actively and 1.5-1.6 s otherwise. The recorded Osiris+ measurements of
      known static positions were within +/-1 mm of the value from the computer
      controlled platform moving the test object. The elliptical motions in 3D were
      tracked to +/-1 mm in two directions (Y,Z), and generally to within +/-2 mm for
      the third direction (X); however, specific marked points could display an error
      of up to 5 mm at certain positions in X. The overall displacement error for the
      3D motion was +/-1 mm with a standard deviation of 2.5 mm. The system performance
      is satisfactory for use in tracking external marker motion during radiotherapy
      treatments.

PMID- 16980677
TI  - Particle matters?

PMID- 16980678
TI  - RBE for mammographic X-ray energies.

PMID- 16980679
TI  - Enhanced biological effectiveness of low energy X-rays and implications for the
      UK breast screening programme.

PMID- 16980680
TI  - More than pancreatitis?

PMID- 16980681
TI  - Applications of magnetic resonance spectroscopy in radiotherapy treatment
      planning.
AB  - Following advances in conformal radiotherapy, a key problem now facing radiation
      oncologists is target definition. While MRI and CT provide images of excellent
      spatial resolution, they do not always provide sufficient contrast to identify
      tumour extent or to identify regions of high cellular activity that might be
      targeted with boost doses. Magnetic resonance spectroscopy (MRS) is an
      alternative approach that holds great promise for aiding target definition for
      radiotherapy treatment planning, and for evaluation of response and recurrence.
      MRS is able to detect signals from low molecular weight metabolites such as
      choline and creatine that are present at concentrations of a few mM in tissue.
      Spectra may be acquired from single voxels, or from a 2D or 3D array of voxels
      using spectroscopic imaging. The current state of the art achieves a spatial
      resolution of 6-10 mm in a scan time of about 10-15 min. Co-registered MR images
      are acquired in the same examination. The method is currently under evaluation,
      in particular in brain (where MRS has been shown to differentiate between many
      tumour types and grades) and in prostate (where cancer may be distinguished from
      normal tissue and benign prostatic hypertrophy). The contrast achieved with MRS,
      based on tissue biochemistry, therefore provides a promising alternative for
      identifying tumour extent and regions of high metabolic activity. It is
      anticipated that MRS will become an essential tool for treatment planning where
      other modalities lack the necessary contrast.

PMID- 16980682
TI  - New developments in MRI for target volume delineation in radiotherapy.
AB  - MRI is being increasingly used in oncology for staging, assessing tumour response
      and also for treatment planning in radiotherapy. Both conformal and intensity
      modulated radiotherapy requires improved means of defining target volumes for
      treatment planning in order to achieve its intended benefits. MRI can add to the
      radiotherapy treatment planning (RTP) process by providing excellent and improved
      characterization of soft tissues compared with CT. Together with its multiplanar
      capability and increased imaging functionality, these advantages for target
      volume delineation outweigh its drawbacks of lacking electron density information
      and potential image distortion. Efficient MR distortion assessment and correction
      algorithms together with image co-registration and fusion programs can overcome
      these limitations and permit its use for RTP. MRI developments using new contrast
      media, such as ultrasmall superparamagnetic iron oxide particles for abnormal
      lymph node identification, techniques such as dynamic contrast enhanced MRI and
      diffusion MRI to better characterize tissue and tumour regions as well as
      ultrafast volumetric or cine MR sequences to define temporal patterns of target
      and organ at risk deformity and variations in spatial location have all increased
      the scope and utility of MRI for RTP. Information from these MR developments may
      permit treatment individualization, strategies of dose escalation and image
      guided radiotherapy. These developments will be reviewed to assess their current
      and potential use for RTP and precision high dose radiotherapy.

PMID- 16980683
TI  - The role of PET/CT scanning in radiotherapy planning.
AB  - The introduction of functional data into the radiotherapy treatment planning
      process is currently the focus of significant commercial, technical, scientific
      and clinical development. The potential of such data from positron emission
      tomography (PET) was recognized at an early stage and was integrated into the
      radiotherapy treatment planning process through the use of image fusion software.
      The combination of PET and CT in a single system (PET/CT) to form an inherently
      fused anatomical and functional dataset has provided an imaging modality which
      could be used as the prime tool in the delineation of tumour volumes and the
      preparation of patient treatment plans, especially when integrated with virtual
      simulation. PET imaging typically using 18F-Fluorodeoxyglucose (18F-FDG) can
      provide data on metabolically active tumour volumes. These functional data have
      the potential to modify treatment volumes and to guide treatment delivery to
      cells with particular metabolic characteristics. This paper reviews the current
      status of the integration of PET and PET/CT data into the radiotherapy treatment
      process. Consideration is given to the requirements of PET/CT data acquisition
      with reference to patient positioning aids and the limitations imposed by the
      PET/CT system. It also reviews the approaches being taken to the definition of
      functional/tumour volumes and the mechanisms available to measure and include
      physiological motion into the imaging process. The use of PET data must be based
      upon a clear understanding of the interpretation and limitations of the
      functional signal. Protocols for the implementation of this development remain to
      be defined, and outcomes data based upon clinical trials are still awaited.

PMID- 16980684
TI  - Localization: conventional and CT simulation.
AB  - Recent developments in imaging and computer power have led to the ability to
      acquire large three dimensional data sets for target localization and complex
      treatment planning for radiation therapy. Conventional simulation implies the use
      of a machine capable of the same mechanical movements as treatment units. Images
      obtained from these machines are essentially two dimensional with the facility to
      acquire a limited number of axial slices to provide patient contours and tissue
      density information. The recent implementation of cone beam imaging on simulators
      has transformed them into three dimensional imaging devices able to produce the
      data required for complex treatment planning. The introduction of computed axial
      tomography (CT) in the 1970s was a step-change in imaging and its potential use
      in radiotherapy was quickly realised. However, it remained a predominantly
      diagnostic tool until modifications were introduced to meet the needs of
      radiotherapy and software was developed to perform the simulation function. The
      comparability of conventional and virtual simulation has been the subject of a
      number of studies at different disease sites. The development of different cross
      sectional imaging modalities such as MRI and positron emission tomography has
      provided additional information that can be incorporated into the simulation
      software by image fusion and has been shown to aid in the delineation of tumours.
      Challenges still remain, particularly in localizing moving structures. Fast
      multislice scanning protocols freeze patient and organ motion in time and space,
      which may lead to inaccuracy in both target delineation and the choice of margins
      in three dimensions. Breath holding and gated respiration techniques have been
      demonstrated to produce four-dimensional data sets that can be used to reduce
      margins or to minimize dose to normal tissue or organs at risk. Image guided
      radiotherapy is being developed to address the interfraction movement of both
      target volumes and critical normal structures. Whichever method of localization
      and simulation is adopted, the role of quality control is important for the
      overall accuracy of the patient's treatment and must be adapted to reflect the
      networked nature of the process.

PMID- 16980685
TI  - Developments in electronic portal imaging systems.
AB  - Verification of geometric accuracy at the time of treatment delivery has always
      been a necessary part of the radiotherapy process. Since the introduction of
      conformal and intensity-modulated radiotherapy, the consequences of patient
      positioning errors are more serious. Portal imaging has played a large part in
      fulfilling the need for improved geometric accuracy. This review examines how
      portal imaging has progressed through the development and evolution of electronic
      portal imaging devices (EPIDs). Changes in technology, including the current
      commercial systems, and how image quality has changed are presented. The clinical
      usage of EPIDs and the technological innovations being devised for further
      improvements in image quality and systems are considered.

PMID- 16980686
TI  - Developments in and experience of kilovoltage X-ray cone beam image-guided
      radiotherapy.
AB  - This paper offers a realistic review of kilovoltage X-ray cone beam tomography
      integrated with the treatment machine for image-guided radiotherapy in the light
      of experience taking a commercial system from prototype development into clinical
      use. It shows that key practicalities cannot be ignored, in particular the
      regular characterization of mechanical flex during gantry rotation, the mapping
      of defects in flat panel image transducers and their response to X-ray exposure.
      The number of X-ray projections and the doses required for clinically useful cone
      beam reconstruction at different therapy sites are considered in the context of
      imaging that is fit for purpose. Three roles for cone beam tomography in
      radiotherapy are identified: patient setup in three dimensions (3D), where even
      low dose cone beam tissue detail is superior to megavoltage imaging; disease
      targeting where, despite wide field scatter and slow scanning, it is possible to
      generate images that are suitable for tumour delineation even at challenging
      sites; adaptive treatment planning, where calibrated cone beam images have been
      shown to provide sufficient target detail to support "plan of the day" selection
      and have the potential for planning with bulk corrections. With frequent use in
      mind, the need to limit patient dose during setup, yet maximize much needed image
      quality in the target zone, is considered. Finally, it is noted that the
      development of cone beam tomography for radiotherapy is far from complete, with X
      ray source, image transducer, reconstruction algorithms and techniques for image
      profile collection still being researched.

PMID- 16980687
TI  - Kilovoltage CT using a linac-CT scanner combination.
AB  - Modern radiotherapy techniques such as intensity modulation are capable of
      generating complex dose distributions whose high dose areas tightly conform to
      the tumour target volume, sparing critical organs even when they are located in
      close proximity. This potential can only be exploited to its full extent when the
      accumulated dose actually delivered over the complete treatment course is
      sufficiently close to the dose computed on the initial CT scan used for treatment
      planning. Exact patient repositioning is mandatory, but also other sources of
      error, e.g. changes of the patient's anatomy under therapy, should be taken into
      account. At the German Cancer Research Center, we use a combination of a linear
      accelerator and a CT scanner installed in one room and sharing the same couch. It
      allows the quantification and correction of interfractional variations between
      planning and treatment delivery. In this paper, we describe treatments of
      prostate, paraspinal and head and neck tumours. All patients were immobilized by
      customized fixation devices and treated in a stereotactic setup. For each
      patient, frequent CT scans were taken during the treatment course. Each scan was
      compared with the original planning CT using manual checks and automatic rigid
      matching algorithms. Depending on the individual case, the adaptation to
      variations was carried out offline after several fractions or in real-time
      between the CT scan and linac irradiation. We discuss the techniques for
      detecting and correcting interfractional errors and outline the procedural steps
      of a linac-CT scanner-supported radiation treatment course.

PMID- 16980688
TI  - Dose-guided radiation therapy with megavoltage cone-beam CT.
AB  - Recent advances in fractionated external beam radiation therapy have increased
      our ability to deliver radiation doses that conform more tightly to the tumour
      volume. The steeper dose gradients delivered in these treatments make it
      increasingly important to set precisely the positions of the patient and the
      internal organs. For this reason, considerable research now focuses on methods
      using three-dimensional images of the patient on the treatment table to adapt
      either the patient position or the treatment plan, to account for variable organ
      locations. In this article, we briefly review the different adaptive methods
      being explored and discuss a proposed dose-guided radiation therapy strategy that
      adapts the treatment for future fractions to compensate for dosimetric errors
      from past fractions. The main component of this strategy is a procedure to
      reconstruct the dose delivered to the patient based on treatment-time portal
      images and pre-treatment megavoltage cone-beam computed tomography (MV CBCT)
      images of the patient. We describe the work to date performed to develop our dose
      reconstruction procedure, including the implementation of a MV CBCT system for
      clinical use, experiments performed to calibrate MV CBCT for electron density and
      to use the calibrated MV CBCT for dose calculations, and the dosimetric
      calibration of the portal imager. We also present an example of a reconstructed
      patient dose using a preliminary reconstruction program and discuss the technical
      challenges that remain to full implementation of dose reconstruction and dose
      guided therapy.

PMID- 16980689
TI  - Image registration and data fusion in radiation therapy.
AB  - This paper provides an overview of image registration and data fusion techniques
      used in radiation therapy, and examples of their use. They are used at all stages
      of the patient management process; for initial diagnosis and staging, during
      treatment planning and delivery, and after therapy to help monitor the patients'
      response to treatment. Most treatment planning systems now support some form of
      interactive or automated image registration and provide tools for mapping
      information, such as tissue outlines and computed dose from one imaging study to
      another. To complement this, modern treatment delivery systems offer means for
      acquiring and registering 2D and 3D image data at the treatment unit to aid
      patient setup. Techniques for adapting and customizing treatments during the
      course of therapy using 3D and 4D anatomic and functional imaging data are
      currently being introduced into the clinic. These techniques require
      sophisticated image registration and data fusion technology to accumulate
      properly the delivered dose and to analyse possible physiological and anatomical
      changes during treatment. Finally, the correlation of radiological changes after
      therapy with delivered dose also requires the use of image registration and
      fusion techniques.

PMID- 16980690
TI  - Urothelial cells malignantly transformed by exposure to cadmium (Cd(+2)) and
      arsenite (As(+3)) have increased resistance to Cd(+2) and As(+3)-induced cell
      death.
AB  - This laboratory has shown that both Cd(+2) and As(+3) can malignantly transform
      human urothelial cells. The present study examined metal resistance and the
      mechanism of cell death when the parental and malignantly transformed UROtsa
      cells were exposed to Cd(+2) and As(+3). It was shown that the malignantly
      transformed UROtsa cells were more resistant to the toxic effects of both metals.
      The assessment of the mode of cell death demonstrated that the parental UROtsa
      cells died by both apoptosis and necrosis when exposed to either metal. It was
      shown that apoptosis was the more prominent mechanism of cell death, accounting
      for over 50% of cell death. Apoptotic cell death was determined by the
      observation of fragmented nuclei using 4',6-diamidino-2-phenylindole staining,
      the formation of a DNA ladder, and the detection of cleaved caspase-3 and caspase
      9 products in the cell lysates. Necrotic cell death was determined by measuring
      the release of lactate dehydrogenase into the growth medium. It was determined
      that the extent of apoptosis of the malignantly transformed UROtsa cells was
      decreased and that the extent of necrosis was increased compared to the parental
      UROtsa cells. These observations are consistent with in vivo studies which
      suggest that As(+3) can act as a tumor promoter during the regeneration of the
      bladder urothelium. The present in vitro studies suggest that As(+3)-induced
      cytotoxicity could set the stage for tissue repair due to its own inherent
      toxicity to normal urothelium, and then subsequently act as a tumor promoter
      during the regeneration process through the stimulation of the regrowth of cells
      that have gained increased resistance to As(+3).

PMID- 16980691
TI  - Polybrominated diphenyl ethers, a group of brominated flame retardants, can
      interact with polychlorinated biphenyls in enhancing developmental
      neurobehavioral defects.
AB  - The present study shows that polybrominated diphenyl ethers (PBDEs) and
      polychlorinated biphenyls (PCBs) can interact and enhance developmental
      neurobehavioral defects when the exposure occurs during a critical stage of
      neonatal brain development. PBDEs are used in large quantities as flame-retardant
      additives in polymers, especially in the manufacture of a great variety of
      electrical appliances, and textiles. In contrast to the well-known persistent
      compounds PCBs and DDT, the PBDEs have been found to increase in the environment
      and in human mother's milk. We have previously shown that low-dose exposure to
      environmental toxic agents such as PCB can cause developmental neurotoxic effects
      when present during a critical stage of neonatal brain development.
      Epidemiological studies indicate the adverse neurobehavioral impact of PCBs.
      Recently, we reported that neonatal exposure to PBDEs causes developmental
      neurotoxic effects. In the present study, 10-day-old Naval Medical Research
      Institute male mice were given one single oral dose of PCB 52 (1.4 micromol/kg
      body weight [bw]) + PBDE 99 (1.4 micromol), PCB 52 (1.4 micromol or 14 micromol),
      or PBDE 99 (1.4 micromol or 14 micromol). Controls received a vehicle (20% fat
      emulsion). Animals exposed to the combined dose of PCB 52 (1.4 micromol) + PBDE
      99 (1.4 micromol) and the high dose of PCB 52 (14 micromol) or PBDE 99 (14
      micromol) showed significantly impaired spontaneous motor behavior and
      habituation capability at the age of 4 and 6 months. The neurobehavioral defects
      were also seen to worsen with age in mice neonatally exposed to PCB 52 + PBDE 99.

PMID- 16980692
TI  - The import competence of a peroxisomal membrane protein is determined by Pex19p
      before the docking step.
AB  - Biogenesis of the mammalian peroxisomal membrane requires the action of Pex3p and
      Pex16p, two proteins present in the organelle membrane, and Pex19p, a protein
      that displays a dual subcellular distribution (peroxisomal and cytosolic). Pex19p
      interacts with most peroxisomal intrinsic membrane proteins, but whether this
      property reflects its role as an import receptor for this class of proteins or a
      chaperone-like function in the assembly/disassembly of peroxisomal membrane
      proteins has been the subject of much controversy. Here, we describe an in vitro
      system particularly suited to address this issue. It is shown that insertion of a
      reporter protein into the peroxisomal membrane is a Pex3p-dependent process that
      does not require ATP/GTP hydrolysis. The system can be programmed with
      recombinant versions of Pex19p, allowing us to demonstrate that Pex19p-cargo
      protein complexes formed in the absence of peroxisomes are the substrates for the
      peroxisomal docking/insertion machinery. Data suggesting that cargo-loaded Pex19p
      displays a much higher affinity for Pex3p than Pex19p alone are also provided.
      These results suggest that soluble Pex19p participates in the targeting of newly
      synthesized peroxisomal membrane proteins to the organelle membrane and support
      the existence of a cargo-induced peroxisomal targeting mechanism for Pex19p.

PMID- 16980693
TI  - Streptococcal mitogenic exotoxin, SmeZ, is the most susceptible M1T1
      streptococcal superantigen to degradation by the streptococcal cysteine protease,
      SpeB.
AB  - Superantigens (SAgs) play an important role in the pathogenesis of severe
      invasive infections caused by Group A Streptococcus (GAS). We had shown earlier
      that the expression of streptococcal cysteine protease SpeB results in partial
      loss of the immune-stimulating activity of the native secreted GAS SAgs, namely
      the streptococcal pyrogenic exotoxins produced by the globally disseminated M1T1
      GAS strain, associated with invasive infections worldwide. In this study, we
      examined the susceptibility of each of the M1T1 recombinant SAgs to degradation
      by rSpeB. Whereas SmeZ was degraded completely within 30 min of incubation with
      rSpeB, SpeG, and SpeA were more resistant and SpeJ was completely unaffected by
      the proteolytic effects of this protease. Proteomic analyses demonstrated that
      the order of susceptibility of the M1T1 SAgs to SpeB proteolysis is unaltered
      when they are present in a mixture that reflects their native physiological
      status. As expected, the degradation of SmeZ abolished its immune stimulatory
      activity. In silico sequence disorder and structural analyses revealed that SmeZ,
      unlike the three other structurally related SAgs, possesses a putative SpeB
      cleavage site within an area of the protein likely to be exposed to the surface.
      The study provides evidence for the effect of subtle structural differences
      between highly similar SAgs on their biological activity.

PMID- 16980694
TI  - Very long-chain fatty acid-containing lipids rather than sphingolipids per se are
      required for raft association and stable surface transport of newly synthesized
      plasma membrane ATPase in yeast.
AB  - The proton-pumping H+-ATPase, Pma1p, is an abundant and very long lived polytopic
      protein of the yeast plasma membrane. Pma1p constitutes a major cargo of the
      secretory pathway and thus serves as a model to study plasma membrane biogenesis.
      Pma1p associates with detergent-resistant membrane domains (lipid "rafts")
      already in the ER, and a lack of raft association correlates with mistargeting of
      the protein to the vacuole, where it is degraded. We are analyzing the role of
      specific lipids in membrane domain formation and have previously shown that
      surface transport of Pma1p is independent of newly synthesized sterols but that
      sphingolipids with C26 very long chain fatty acid are crucial for raft
      association and surface transport of Pma1p (Gaigg, B., Timischl, B., Corbino, L.,
      and Schneiter, R. (2005) J. Biol. Chem. 280, 22515-22522). We now describe a more
      detailed analysis of the function that sphingolipids play in this process. Using
      a yeast strain in which the essential function of sphingolipids is substituted by
      glycerophospholipids containing C26 very long chain fatty acids, we find that
      sphingolipids per se are dispensable for raft association and surface delivery of
      Pma1p but that the C26 fatty acid is crucial. We thus conclude that the essential
      function of sphingolipids for membrane domain formation and stable surface
      delivery of Pma1p is provided by the C26 fatty acid that forms part of the yeast
      ceramide.

PMID- 16980695
TI  - Cluster-based network model for time-course gene expression data.
AB  - We propose a model-based approach to unify clustering and network modeling using
      time-course gene expression data. Specifically, our approach uses a mixture model
      to cluster genes. Genes within the same cluster share a similar expression
      profile. The network is built over cluster-specific expression profiles using
      state-space models. We discuss the application of our model to simulated data as
      well as to time-course gene expression data arising from animal models on
      prostate cancer progression. The latter application shows that with a combined
      statistical/bioinformatics analyses, we are able to extract gene-to-gene
      relationships supported by the literature as well as new plausible relationships.

PMID- 16980696
TI  - Causal inference for non-mortality outcomes in the presence of death.
AB  - Evaluation of the causal effect of a baseline exposure on a morbidity outcome at
      a fixed time point is often complicated when study participants die before
      morbidity outcomes are measured. In this setting, the causal effect is only well
      defined for the principal stratum of subjects who would live regardless of the
      exposure. Motivated by gerontologic researchers interested in understanding the
      causal effect of vision loss on emotional distress in a population with a high
      mortality rate, we investigate the effect among those who would live both with
      and without vision loss. Since this subpopulation is not readily identifiable
      from the data and vision loss is not randomized, we introduce a set of
      scientifically driven assumptions to identify the causal effect. Since these
      assumptions are not empirically verifiable, we embed our methodology within a
      sensitivity analysis framework. We apply our method using the first three rounds
      of survey data from the Salisbury Eye Evaluation, a population-based cohort study
      of older adults. We also present a simulation study that validates our method.

PMID- 16980697
TI  - Prevalence of aadA1 and dfrA15 class 1 integron cassettes and SXT circulation in
      Vibrio cholerae O1 isolates from Africa.

PMID- 16980698
TI  - dfrA25, a novel trimethoprim resistance gene from Salmonella Agona isolated from
      a human urine sample in Brazil.
AB  - OBJECTIVES: To describe a novel trimethoprim resistance gene, designated dfrA25,
      which was detected as a gene cassette within a class 1 integron in Salmonella
      Agona. METHODS: The gene was cloned into Escherichia coli MT102 and resistance to
      10 different antimicrobial drugs was measured. A phylogenetic tree was
      constructed based on representative trimethoprim-resistance-mediating DfrA
      proteins retrieved from GenBank. Filter-mating experiments and Southern blots of
      plasmid preparations were performed with the donor and selected transconjugants.
      RESULTS AND CONCLUSIONS: dfrA25 encodes a dihydrofolate reductase of 157 amino
      acids with closest identity (85%) to dfrA5 dihydrofolate reductase. dfrA25 was
      located on a transferable plasmid (approximately 150 kb) that also harboured the
      tetracycline resistance gene tet(A).

PMID- 16980699
TI  - Re: 'Occupational exposures and risks of liver cancer among Shanghai female
      textile workers--a case-cohort study'.

PMID- 16980700
TI  - Cohort profile: the Medical Research Council Cognitive Function and Ageing Study
      (CFAS).

PMID- 16980702
TI  - Repression of nitrate uptake by replacement of Asp105 by asparagine in AtNRT3.1
      in Arabidopsis thaliana L.
AB  - An Arabidopsis mutant (rnc1) with a mutation at the 313th nucleotide from the
      translational start site of AtNRT3.1 was isolated. The mutation resulted in the
      replacement of aspartate by asparagine at the 105th amino acid in a region
      conserved among higher plants. In the rnc1 mutant, both the nitrate
      concentrations in plants and the nitrate uptake from the medium were <13%
      compared with those of the wild type, while AtNRT3.1 mRNA was accumulated
      similarly and both AtNRT1.1 and AtNRT2.1 mRNA were decreased. These results
      suggest that the replacement of Asp105 in AtNRT3.1 markedly reduces nitrate
      uptake and accumulation.

PMID- 16980703
TI  - Active NDH-1 complexes from the cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - We identified eight bands by staining native gels for NADPH-nitroblue tetrazolium
      oxidoreductase activity after electrophoresis of n-dodecyl-beta-d-maltoside
      treated membranes of Synechocystis sp. strain PCC 6803. Among them, bands A, C, D
      and E were attributed to the activity of NADPH dehydrogenase (NDH-1). Band A is a
      highly active supercomplex of NDH-1 (about 1,000 kDa) that was absent in the
      DeltandhD1/D2 mutant and was suppressed under low CO(2). Band C was induced under
      low CO(2) or in the DeltandhD1/D2 mutant and was converted to bands D and E.
      Bands A and C appear to be an NDH-1L dimer and NDH-1M, respectively, with
      subunits essential for the activity.

PMID- 16980704
TI  - Gene trapping in Arabidopsis reveals genes involved in vascular development.
AB  - The procambium is made up of stem cells that give rise to various vascular cells
      in plants. To understand the molecular nature of procambium cells, we tried to
      identify genes that characterize procambium cells using Arabidopsis gene trap
      lines. Among 26,000 gene trap lines, we found 67 lines in which beta
      glucuronidase (GUS) staining occurred along vascular tissues in cotyledons and/or
      adult leaves. Although four gene trap lines showed procambium-preferential GUS
      expression, their expression patterns differed from each other during procambium
      development in root tips and young rosette leaves. Genomic regions flanking the
      gene trap insertion points in 25 of the 67 lines were determined, including three
      lines showing preferential GUS staining of the procambium. The three procambium
      related genes encoded PINHEAD, katanin and an unknown DUF740 domain-containing
      protein. We discuss procambium development based on the functions and the
      differential GUS staining patterns of the procambium-related genes.

PMID- 16980705
TI  - Low-dose treatment with polybrominated diphenyl ethers (PBDEs) induce altered
      characteristics in MCF-7 cells.
AB  - Polybrominated diphenyl ethers (PBDEs) are hydrophobic and persistent additive
      flame retardants that seemingly transfer into environmental compartments where
      they bioaccumulate i.e. in human biota. We examined the micronucleus-forming
      activities of low-dose PBDEs (congeners 47, 99, 153, 183 or 209) in MCF-7 cells
      along with their ability to modulate growth, cell biochemistry [by infrared (IR)
      microspectroscopy], clonogenic survival or quantitative expression of cytochrome
      P450 isoenzymes (CYP1A1, CYP1A2 and CYP1B1), cyclin-dependent kinase inhibitor 1A
      [CDKN1A (P21(WAF1/CIP1))], B-cell leukaemia/lymphoma-2 (BCL-2) and Bcl-2
      associated X (BAX). Elevations in micronucleus formation were observed following
      treatment with 10(-12) to 10(-9) M PBDE concentrations despite the fact that less
      than one-fourth of the concentration of each test agent administered partitioned
      out of the media and into the incubating cells. However, low-dose treatment
      levels remained within the range of reported concentrations measured in UK serum
      samples collected in 2003. Clonogenic survival and gene expression was unaltered
      following 10(-12) to 10(-9) M PBDE treatment but significant (P < 0.05)
      elevations in growth kinetics were observed. Significant alterations in IR cell
      spectra were associated with treatments, and plotted clusters following principal
      component analysis highlighted these changes. Whether such in vitro effects point
      to an underlying ability of PBDEs to initiate and drive target-cell alterations
      in vivo now needs to be addressed.

PMID- 16980706
TI  - Neutron dose measurements with the GSI ball at high-energy accelerators.
AB  - A moderator-type neutron monitor containing pairs of TLD 600/700 elements
      (Harshaw) modified with the addition of a lead layer (GSI ball) for the
      measurement of the ambient dose equivalent from neutrons at medium- and high
      energy accelerators, is introduced in this work. Measurements were performed with
      the Gesellschaft fur Schwerionenforschung (GSI) ball as well as with conventional
      polyethylene (PE) spheres at the high-energy accelerator SPS at European
      Organization for Nuclear Research [CERN (CERF)] and in Cave A of the heavy-ion
      synchrotron SIS at GSI. The measured dose values are compared with dose values
      derived from calculated neutron spectra folded with dose conversion coefficients.
      The estimated reading of the spheres calculated by means of the response
      functions and the neutron spectra is also included in the comparison. The
      analysis of the measurements shows that the PE/Pb sphere gives an improved
      estimate on the ambient dose equivalent of the neutron radiation transmitted
      through shielding of medium- and high-energy accelerators.

PMID- 16980707
TI  - Individual monitoring based on magnesium borate.
AB  - Valuable features of magnesium borate sintered solid thermoluminescence
      dosemeters (TLDs), such as near tissue- equivalence, high sensitivity, and good
      performances for X, gamma, beta and neutron dosimetry, were developed and
      produced by the Institute of Nuclear Sciences, Vinca. These features form the
      basis for using this type of TLDs successfully for legal personal dosimetry
      control in Serbia for the past 27 y. The dosimetric properties of this TL
      material are presented in this study.

PMID- 16980708
TI  - Improvement and calibration of a SSNT personal dosemeter and study of importance
      of albedo factor for dose calculation.
AB  - The Neutriran albedo neutron dosemeter has been improved and calibrated for
      neutron personal dosimetry. The Monte Carlo code MCNP4b was used to calculate the
      thermal neutrons backscattered from the body (albedo factor). Backscattering from
      the wall, ceiling and floor in calibration room was considered also via
      simulation by MCNP4C. A semi automated counting system applying a high-resolution
      scanner was used for counting of tracks. An 241Am source was used to produce
      similar alpha particles from 10B (n,alpha)7Li reaction for the optimisation of
      scanner parameters to distinguish and separate the tracks in SSNTD, which lead to
      a better distinction between etched alpha tracks and, consequently, a higher
      linear region of dose characteristic.

PMID- 16980709
TI  - Non-invasive prediction of fluid responsiveness during major hepatic surgery.
AB  - BACKGROUND: The aim of this study was to evaluate potential predictors of fluid
      responsiveness obtained during major hepatic surgery. The predictors studied were
      invasive monitoring of intravascular pressures (radial and pulmonary artery
      catheter), including direct measurement of respiratory variation in arterial
      pulse pressure (PPVart), transoesophageal echocardiography (TOE), and non
      invasive estimates of PPVart from the infrared photoplethysmography waveform from
      the Finapres (PPVfina) and the pulse oximetry waveform (PPVsat). METHODS: We
      conducted a prospective study of 54 fluid challenges (250 ml colloid) given for
      haemodynamic instability in eight patients undergoing hepatic resection. Fluid
      responsiveness was defined as an increase in stroke volume index (SVI) >or=10%.
      The following variables were recorded before each fluid challenge: right atrial
      pressure (RAP), pulmonary artery occlusion pressure (PAOP), PPVart, PPVfina,
      PPVsat, and the TOE-derived variables left ventricular end-diastolic area index
      (LVEDAI), early/late (E/A) diastolic filling wave ratio, deceleration time of the
      E wave (MDT) of mitral flow and the systolic fraction of the pulmonary venous
      flow (SF). RESULTS: Only PPVfina, PPVart (both P<0.001), PPVsat (P=0.02), LVEDAI
      and MDT (both P=0.04) were different in responder vs non-responder fluid
      challenges. The areas under the receiver operating characteristic (ROC) curves
      were 0.81 (PPVfina), 0.79 (PPVart), 0.70 (LVEDAI), 0.68 (PPVsat and MDT), 0.63
      (RAP), 0.62 (E/A), 0.55 (PAOP) and 0.42 (SF). The areas under the ROC curves for
      RAP, E/A, PAOP and SF were significantly less than that for PPVfina (P<0.05 in
      each case). Only PPVart (r=0.59, P=0.0001) and PPVfina (r=0.56, P=0.0001)
      correlated with the fluid challenge-induced changes in SVI. CONCLUSIONS: PPVart
      and PPVfina predict fluid responsiveness during major hepatic surgery. This
      suggests that intraoperative monitoring of fluid responsiveness may be
      implemented simply and non-invasively.

PMID- 16980710
TI  - Development of a rating scale to predict the severity of alcohol withdrawal
      syndrome.
AB  - AIM: Various factors that may influence the severity of the alcohol withdrawal
      syndrome (AWS) have been identified. We tested the predictive value of these
      factors compiled in a newly developed scale, LARS (Luebeck alcohol withdrawal
      risk scale). METHOD: A total of 100 individuals (81 males, 19 females, mean age:
      47.6 +/- 9.9 years) consecutively transferred to inpatient detoxification were
      included in this prospective study. All fulfilled the ICD-10 criteria for alcohol
      dependence. The LARS was applied at the time of admission. The course of the AWS
      was assessed by AWS-scale at least every 4 h. The maximum AWS-score was taken as
      indicator of the severity of AWS. RESULTS: The mean AWS-score(max) was 6.5 +/-
      3.3. In all 20% of the patients developed a severe AWS (AWS-score(max) > or =10).
      The maximum score usually occurred within 36 h after the last drink. A short
      version, the LARS11, was developed by statistically grounded item reduction. The
      optimal cut-off of the LARS11 was calculated as 10. The positive predictive value
      for severe AWS was 76%, while the negative predictive value was 98.7%. The
      sensitivity and specificity were high (95 or 92.5%, respectively). CONCLUSION:
      LARS11 assessed immediately before detoxification appears to provide a useful
      estimate of mild/moderate versus severe AWS, and is now ready to be validated in
      an independent sample.

PMID- 16980711
TI  - The total body mass of fatty acid ethyl esters in skeletal muscles following
      ethanol exposure greatly exceeds that found in the liver and the heart.
AB  - AIMS: Skeletal muscle appears to be susceptible to chronic and acute excess
      alcohol intake, giving rise to alcoholic myopathy, a common disease among
      alcoholics. Fatty acid ethyl esters (FAEE), non-oxidative metabolites of ethanol,
      have been shown to be toxic to cells in vitro and in vivo. We hypothesized that
      accumulation of FAEE in skeletal muscle could contribute to the development of
      alcoholic myopathy. METHODS: Male wistar rats were treated either with 75 mmol
      ethanol/kg body weight or saline, in the fed state or starved for 1 or 2 days
      before administration. Rats were thus divided into the following groups: fed
      saline (n = 8); fed-ethanol (n = 8); starved 1 day, saline (n = 8); starved 1
      day, ethanol (n = 9); starved 2 days, saline (n = 7); and starved 2 days, ethanol
      (n = 8). At the end of the incubation, skeletal muscles (abdominal and
      gastrocnemius), liver, and heart were isolated and processed for FAEE isolation
      and analysis by gas chromatography-mass spectrometry (GC-MS). RESULTS: Total mass
      of FAEE in the muscles was much greater than that found in the liver and the
      heart. In general, the animals that were fasted for 1 day and received ethanol
      had the highest FAEE levels among the three groups of animals. The major ethyl
      ester species in all cases were ethyl 16:0, ethyl 18:0, ethyl 18:1 n-9, and ethyl
      18:2 n-6. Ethyl 20:4 n-6 and ethyl 22:6 n-3 were also present, except in the
      fasted 1-day group, where ethyl 22:6 disappeared, though it reappeared in the
      fasted 2-day group. CONCLUSION: These findings demonstrate that skeletal muscles
      contain high levels of FAEE that are synthesized in the body after ethanol
      exposure. The concentration of FAEE in skeletal muscle in this study was very
      similar to FAEE concentration in the liver. This differs from previous studies
      suggesting a low concentration of skeletal muscle FAEE with ethanol exposure.

PMID- 16980712
TI  - Whole-genome microarray in Arabidopsis facilitates global analysis of retained
      introns.
AB  - Alternative splicing (AS) is an important post-transcriptional regulatory
      mechanism that can increase protein diversity and affect mRNA stability.
      Different types of AS have been observed; these include exon skipping,
      alternative donor or acceptor site and intron retention. In humans, exon skipping
      is the most common type while intron retention is rare. In contrast, in
      Arabidopsis, intron retention is the most prevalent AS type (approximately 40%).
      Here we show that direct transcript expression analysis using high-density
      oligonucleotide-based whole-genome microarrays (WGAs) is particularly amenable
      for assessing global intron retention in Arabidopsis. By applying a novel
      algorithm retained introns are detected in 8% of the transcripts examined. A
      sampling of 14 transcripts showed that 86% can be confirmed by RT-PCR. This rate
      of detection predicts an overall total AS rate of 20% for Arabidopsis compared
      with 10-22% based on EST/cDNA-based analysis. These findings will facilitate
      monitoring constitutive and dynamic whole-genome splicing on the next generation
      WGA slides.

PMID- 16980713
TI  - Search and classification of potential minisatellite sequences from bacterial
      genomes.
AB  - We used the method of Information Decomposition developed by us to identify the
      latent dinucleotide periodicity regions in bacterial genomes. The number of
      potential minisatellite sequences obtained at high level of statistical
      significance was 454. Then we classified the periodicity matrices and obtained 45
      classes. We used the other new method developed by us--Modified Profile Analysis-
      to reveal more periodic sequences in the presence of indels using the classes
      obtained. The number of sequences found by combination of these two methods was
      3949. Most of them cannot be revealed by other methods including dynamic
      programming and Fourier transformation.

PMID- 16980714
TI  - Genomic instability of the DYZ1 repeat in patients with Y chromosome anomalies
      and males exposed to natural background radiation.
AB  - We assessed genomic instability of 3.4 kb DYZ1 repeat arrays in patients
      encompassing prostate cancer (PC), cases of repeated abortion (RA) and males
      exposed to natural background radiation (NBR) using real-time PCR and
      fluorescence in situ hybridization (FISH). Normal males showed DYZ1 copies
      ranging from 3000 to 4300, RA, 0-2237; PC, 550; and males exposed to NBR, 1577
      5700. FISH showed organizational variation of DYZ1 in these samples
      substantiating the data obtained from real-time PCR. Of the 10 RA samples, 7 were
      found to be affected of which, 5 showed deletion of 265 bp from nt 25 to 290 and
      773 bp from 1347 to 2119 and 2 showed deletion of 275 bp from nt 3128 to 3402.
      Copy number variation of DYZ1 in these males correlated with genetic
      constrains/anomalies. Although precise mechanisms of genomic instability of DYZ1
      remains unclear, we construe that this repeat plays a critical role in
      maintaining the structural integrity of the Y chromosome, possibly by absorbing
      the load of mutations. This may be used as a marker system to analyze genetic
      integrity of the DYZ1 repeat array(s) across the spectrum of patients.

PMID- 16980715
TI  - Identification of an extracellular acid trehalase and its gene involved in fungal
      pathogenesis of Metarizium anisopliae.
AB  - Trehalose is the main sugar in the haemolymph of insects and is a key nutrient
      source for an insect pathogenic fungus. Secretion of trehalose-hydrolysing
      enzymes may be a prerequisite for successful exploitation of this resource by the
      pathogen. An acid trehalase [EC 3.2.1.28] was purified to homogeneity from a
      culture of a locust-specific pathogen, Metarhizium anisopliae, and its properties
      were characterized. The gene (ATM1) of this acid trehalase was also isolated. The
      pure enzyme can efficiently hydrolyze haemolymph trehalose into glucose in vitro.
      The new acid trehalase appearing in the haemolymph of Locusta migratoria infected
      with M. anisopliae had the same pI and substrate specificity as the purified
      fungal acid trehalase, and the concentration of trehalose in the haemolymph
      decreased sharply after infection. RT-PCR also revealed the ATM1 gene's
      expression in the haemolymph of the infected insects. Our results indicated that
      the acid trehalase may serve as an "energy scavenger" and deplete blood trehalose
      during fungal pathogenesis.

PMID- 16980716
TI  - Heart involvement in autoimmune rheumatic diseases: the "phantom of the opera".

PMID- 16980717
TI  - Primary myocardial involvement in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a connective tissue disease characterized by diffuse
      vascular lesions and fibrosis. Primary myocardial involvement is common in SSc
      and, when clinically evident, appears as a poor prognostic factor. An increasing
      body of evidence suggests that myocardial involvement is due, at least in part,
      to microcirculation impairment with abnormal vasoreactivity, with or without
      associated structural abnormalities of the small coronary arteries or arterioles.
      Using conventional methods, myocardial perfusion impairment, systolic and
      diastolic left ventricular dysfunction and right ventricular dysfunction have
      been reported in SSc. Recently, tissue Doppler echocardiography and magnetic
      resonance imaging have confirmed these results. Vasodilators, such as calcium
      channel blockers and angiotensin converting enzyme inhibitors, improve both
      myocardial perfusion and function abnormalities.

PMID- 16980718
TI  - The heart in dermatomyositis and polymyositis.
AB  - Cardiovascular manifestations constitute a major cause of death in myositis.
      Despite this, clinically manifest cardiac involvement in polymyositis and
      dermatomyositis is relatively rare. In contrast, subclinical manifestations are
      frequently reported and are predominated by conduction abnormalities and
      arrhythmias detected by ECG. The most frequently reported clinically overt
      manifestations are congestive heart failure, conduction abnormalities, that may
      lead to complete heart block, and coronary artery disease. The underlying
      pathophysiological mechanisms that may cause cardiac manifestations involve
      myocarditis and coronary artery disease as well as involvement of the small
      vessels of the myocardium.

PMID- 16980719
TI  - Pulmonary arterial hypertension and rheumatic diseases--from diagnosis to
      treatment.
AB  - Survival rates in pulmonary arterial hypertension (PAH) associated with rheumatic
      diseases, in particular connective tissue diseases such as systemic sclerosis,
      are even lower than in idiopathic PAH. These low survival rates highlight the
      need for early diagnosis and treatment in these patients. Transthoracic Doppler
      echocardiography is most often used for diagnostic screening of patients at risk.
      Other screening tests are serum pro-brain-natriuretic peptide (pro-BNP) and
      diffusion capacity for carbon monoxide (DLCO), which appear to be changed early
      in the course of the PAH associated with connective tissue diseases. The
      diagnosis needs to be confirmed by right heart catheterization, which is
      recommended in all patients with suspected PAH. Besides the conventional
      background therapy, a number of specific therapies have been evaluated in
      randomized controlled trials in the recent years. These therapies include
      prostacyclins and prostacyclin analogues, endothelin-receptor antagonists and
      phosphodiesterase-5 inhibitors. Response to treatment can be measured by exercise
      capacity (e.g. 6 min walk distance) and pro-BNP, although certain aspects of
      validation for these outcome measures are lacking in PAH associated with
      connective tissue diseases.

PMID- 16980720
TI  - Cardiac imaging in rheumatic diseases.
AB  - The majority of the imaging techniques in cardiology could be applied in
      rheumatic diseases (RDs), such as echocardiography, single-photon emission
      computed tomography (SPECT), radionuclide ventriculography, angiography,
      cardiovascular MRI and CT. Inflammatory pericardial involvement is the most
      common cardiac manifestation in various forms of RD. Echocardiography is the gold
      standard for diagnosis of pericardial abnormalities, demonstrating location and
      amount of pericardial effusion. Cardiac MRI and CT can be used to assess the
      features of pericardial effusions and pericardial structures. In patients with
      valvular heart disease in RD, transoesophageal echocardiography is a superior
      method and offers reliable information about valve morphology, the severity of
      the disease and left ventricular (LV) function. In addition, cardiac MRI is a
      valuable tool for the evaluation of valvular stenosis and regurgitation severity.
      Myocardial involvement in RD is demonstrated by abnormalities in LV size and
      function, indicating myocardial inflammation. In these patients Doppler
      echocardiography and myocardial tissue imaging can provide essential diagnostic
      information. Both LV angiography and cardiac MRI can provide reliable information
      on LV size, function and mass. In patients with coronary disease associated with
      RD, LV ejection fraction and ventricular wall motion can be assessed by
      echocardiography, radionuclide ventriculography, gated SPECT and MRI. Three
      dimensional (3D) echocardiography is considered superior to 2D echocardiographic
      techniques. Stress echocardiography is the most used method for detection of
      myocardial ischaemia. The only accurate visualization of the coronary arteries is
      by selective coronary arteriography, which remains the gold standard. Although
      new non-invasive techniques have been developed, including CT and MRI
      angiography, some limitations apply.

PMID- 16980721
TI  - Invasive techniques--from diagnosis to treatment.
AB  - Invasive diagnostic and therapeutic techniques are indispensable for the
      diagnosis and interventional treatment of coronary artery disease, valvular
      involvement and, in particular, if the specific components of the inflammatory or
      degenerative processes in rheumatic disease are to be identified in the different
      components of the heart. Although impairment of cardiac function and ischaemia
      can be suspected also by non-invasive techniques, coronary involvement needs the
      final proof by angiography. Endomyocardial or epicardial biopsy identifies the
      key players of autoreactivity: the infiltrating cells and the bound and
      circulating antibodies. Before corticoid treatment is started, a viral or
      microbial aetiology has to be excluded at the site of cardiac inflammation. This
      again can only be done by the analysis of cardiac tissue samples.

PMID- 16980722
TI  - Cardiac arrhythmias and conduction disturbances in autoimmune rheumatic diseases.
AB  - Rhythm and conduction disturbances and sudden cardiac death (SCD) are important
      manifestations of cardiac involvement in autoimmune rheumatic diseases (ARDs). In
      patients with rheumatoid arthritis (RA), a major cause of SCD is atherosclerotic
      coronary artery disease, leading to acute coronary syndrome and ventricular
      arrhythmias. In systemic lupus erythematosus (SLE), sinus tachycardia, atrial
      fibrillation and atrial ectopic beats are the major cardiac arrhythmias. In some
      cases, sinus tachycardia may be the only manifestation of cardiac involvement.
      The most frequent cardiac rhythm disturbances in systemic sclerosis (SSc) are
      premature ventricular contractions (PVCs), often appearing as monomorphic, single
      PVCs, or rarely as bigeminy, trigeminy or pairs. Transient atrial fibrillation,
      flutter or paroxysmal supraventricular tachycardia are also described in 20-30%
      of SSc patients. Non-sustained ventricular tachycardia was described in 7-13%,
      while SCD is reported in 5-21% of unselected patients with SSc. The conduction
      disorders are more frequent in ARD than the cardiac arrhythmias. In RA,
      infiltration of the atrioventricular (AV) node can cause right bundle branch
      block in 35% of patients. AV block is rare in RA, and is usually complete. In SLE
      small vessel vasculitis, the infiltration of the sinus or AV nodes, or active
      myocarditis can lead to first-degree AV block in 34-70% of patients. In contrast
      to RA, conduction abnormalities may regress when the underlying disease is
      controlled. In neonatal lupus, 3% of infants whose mothers are antibody positive
      develop complete heart block. Conduction disturbances in SSc are due to fibrosis
      of sinoatrial node, presenting as abnormal ECG, bundle and fascicular blocks and
      occur in 25-75% of patients.

PMID- 16980723
TI  - The heart and cardiovascular manifestations in rheumatoid arthritis.
AB  - Cardiovascular features in rheumatoid arthritis (RA) are common. Among those are
      the classical extra-articular features that not only include pericarditis,
      cardiomyopathy/myocarditis, cardiac amyloidosis, coronary vasculitis, arrhythmia
      and valve diseases, but also congestive heart failure and ischaemic heart disease
      which are found more frequently and are associated with an increased mortality
      compared with the general population. This overview discusses the epidemiological
      aspects of these cardiovascular diseases and their relevance for diagnosis and
      treatment of RA.

PMID- 16980724
TI  - Nailfold capillaroscopy is useful for the diagnosis and follow-up of autoimmune
      rheumatic diseases. A future tool for the analysis of microvascular heart
      involvement?
AB  - Raynaud's phenomenon (RP) represents the most frequent clinical aspect of
      cardio/microvascular involvement and is a key feature of several autoimmune
      rheumatic diseases. Moreover, RP is associated in a statistically significant
      manner with many coronary diseases. In normal conditions or in primary RP
      (excluding during the cold-exposure test), the normal nailfold capillaroscopic
      pattern shows a regular disposition of the capillary loops along with the
      nailbed. On the contrary, in subjects suffering from secondary RP, one or more
      alterations of the capillaroscopic findings should alert the physician of the
      possibility of a connective tissue disease not yet detected. Nailfold
      capillaroscopy (NV) represents the best method to analyse microvascular
      abnormalities in autoimmune rheumatic diseases. Architectural disorganization,
      giant capillaries, haemorrhages, loss of capillaries, angiogenesis and avascular
      areas characterize >95% of patients with overt scleroderma (SSc). The term 'SSc
      pattern' includes, all together, these sequential capillaroscopic changes typical
      to the microvascular involvement in SSc. The capillaroscopic aspects observed in
      dermatomyositis and in the undifferentiated connective tissue disease are
      generally reported as 'SSc-like pattern'. Effectively, and early in the disease,
      the peripheral microangiopathy may be well recognized and studied by nailfold
      capillaroscopy, or better with nailfold video capillaroscopy (NVC). The early
      differential diagnosis between primary and secondary RP is the best advantage NVC
      may offer. In addition, interesting capillaroscopic changes have been observed in
      systemic lupus erythematosus, anti-phospholipid syndrome and Sjogren's syndrome.
      Further epidemiological and clinical studies are needed to better standardize the
      NCV patterns. In future, the evaluation of nailfold capillaroscopy in autoimmune
      rheumatic diseases might represent a tool for the prediction of microvascular
      heart involvement by considering the systemic microvascular derangement at the
      capillary nailfold.

PMID- 16980725
TI  - Heart involvement in systemic lupus erythematosus, anti-phospholipid syndrome and
      neonatal lupus.
AB  - Cardiac involvement is one of the main complications substantially contributing
      to the morbidity and mortality of patients suffering from systemic autoimmune
      diseases. All the anatomical heart structures can be affected, and multiple
      pathogenic mechanisms have been reported. Non-organ-specific autoantibodies have
      been implicated in immune complex formation and deposition as the initial
      triggers for inflammatory processes responsible for Libman-Sacks verrucous
      endocarditis, myocarditis and pericarditis. Anti-phospholipid antibodies have
      been associated with thrombotic events in coronary arteries, heart valve
      involvement and intra-myocardial vasculopathy in the context of primary and
      secondary anti-phospholipid syndrome. Antibodies-SSA/Ro and anti-SSB/La antigens
      play a major pathogenic role in affecting the heart conduction tissue leading to
      the electrocardiographic abnormalities of the neonatal lupus syndrome and have
      been closely associated with endocardial fibroelastosis.

PMID- 16980726
TI  - Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway
      regulate 3T6 fibroblast growth.
AB  - Eicosanoids participate in the regulation of cellular proliferation. Thus, we
      observed that prostaglandin E(2) interaction with membrane receptors is involved
      in the control of 3T6 fibroblast growth induced by serum. However, our results
      suggested that another arachidonic acid pathway might be implicated in these
      events. Our results show that 3T6 fibroblasts synthesized hydroxyeicosatetraenoic
      acids (HETEs) such as 12-HETE through the cytochrome P-450 (CYP450) pathway.
      However, 3T6 fibroblasts did not produce leukotriene B(4) (LTB(4)), and
      lipoxygenase inhibitors and LT antagonists failed to inhibit 3T6 fibroblast
      growth induced by FBS. In contrast, we observed that CYP450 inhibitors such as
      SKF-525A, 17-octadecynoic acid, 1-aminobenzotriazole, and 6-(2
      propargyloxyphenyl)hexanoic acid reduced 12(S)-HETE levels, 3T6 fibroblast
      growth, and DNA synthesis induced by FBS. The impairment of DNA synthesis and 3T6
      fibroblast growth induced by SKF-525A were reversed by exogenous addition of
      HETEs. Moreover, we report that 5-HETE, 12(S)-HETE, and 15(S)-HETE are mitogenic
      on 3T6 fibroblast in the absence of another growth factor, and this effect was
      dependent on the activation of the phosphatidylinositol-3-kinase pathway. In
      conclusion, our results show that HETEs, probably produced by CYP450, are
      involved in the control of 3T6 fibroblast growth.

PMID- 16980727
TI  - A review of skin and the effects of aging on skin structure and function.
AB  - As the most visible and vulnerable organ of the human body, the skin is
      anatomically and functionally affected by aging. Maintaining skin integrity
      starts with understanding skin anatomy, physiology, and function and recognizing
      conditions as well as aspects of care that may affect structure and function.
      Research suggests that appropriate skin cleansing procedures and protection, as
      well as nutritional and environmental interventions, may help reduce some of the
      effects of aging and have positive psychological and health outcomes. Optimizing
      skin health in the elderly will help maintain its integrity and, as such, should
      be the first step in any wound prevention program.

PMID- 16980728
TI  - Preventing skin tears in a nursing and rehabilitation center: an
      interdisciplinary effort.
AB  - Skin tears are painful, traumatic wounds that result from the separation of the
      epidermis from the dermis. To assess the clinical effectiveness of a preventive
      skin care protocol, 13-month retrospective pre-intervention data collection
      followed by 15-month post-intervention skin tear incidence data collection was
      conducted among all patients in a 209-bed urban nursing and rehabilitation
      center. The preventive skin care strategies implemented - staff education, skin
      sleeves and padded side rails for high-risk patients, gentle skin cleansers, and
      lotion - were selected by facility staff members and the multidisciplinary skin
      team. Nosocomial skin tear data were obtained by reviewing incident reports.
      Following implementation of the prevention protocols, the number of skin tears
      changed from a mean of 18.7 to a mean of 8.73 per month (P <0.001). The average
      monthly reduction in nosocomial skin tears was projected to reduce the dressing
      and labor costs of managing these wounds an average of 1,698 dollars per month
      (18,168.60 dollars annually). The results of this study confirm previously
      reported research suggesting that the effects of implementing a comprehensive
      skin care protocol can persist, reducing the incidence of nosocomial skin tears
      and their associated risks and costs. Prospective cost-effectiveness studies to
      confirm these findings are needed.

PMID- 16980729
TI  - Diabetes mellitus and the elderly: special considerations for foot ulcer
      prevention and care.
AB  - The risk of lower extremity amputation in persons with diabetes mellitus
      increases with advanced age, necessitating clinical vigilance. Individualized and
      comprehensive prevention efforts are required to address the complicated and
      diverse nature of the diabetic foot in the elderly patient, including promotion
      of lifestyle changes to offset diabetes, attention to cognitive deficits and
      economic limitations, and provision of foot care education and management (eg,
      emphasizing the need for appropriate foot wear). If an ulcer develops,
      physiologic and socioeconomic factors may influence its clinical presentation,
      assessment, diagnosis, and treatment. To help ulcer-related complications and
      prevent lower leg amputations, clinicians must address diabetes management; the
      cost of supplies; the importance of offloading, nutrition, and exercise; and
      challenges inherent to impaired eyesight, dexterity, and ability to self-care. A
      multidisciplinary approach is recommended. Additional research to enhance
      understanding of practice parameters in this population is needed to help
      clinicians manage the increasing numbers of older adults with diabetes mellitus.

PMID- 16980730
TI  - Venous leg ulcers in the elderly patient: associated stress, social support, and
      coping.
AB  - Although psychosocial issues in wound management are critical considerations when
      formulating diagnostic and treatment algorithms, they frequently are overlooked.
      Clinician consideration and evaluation of associated stresses, social support,
      and coping are particularly important when caring for elderly patients with
      recalcitrant venous ulcers. The Health Belief Model and health locus of control
      may help explain patient responses to health issues. The psychosocial effects of
      chronic illness, emotional impact of pain, physiological responses to stress, and
      issues related to treatment adherence must be considered. Recent research has
      contributed substantially to understanding of these concerns in the general
      patient population and in persons with venous ulcers. However, quantitative data
      are limited and studies examining the effects of educational level, ethnicity,
      socio-economic status, and clinician-patient relationships on psychosocial health
      in general, and wound healing in particular, are needed. Despite these
      limitations, increased awareness of the psychosocial dynamic in elderly patients
      should be integral to the wound care protocol.

PMID- 16980731
TI  - [The role of the plasmapheresis in the treatment of patients with acute
      intestinal ileus].
AB  - Efficiency of the extracorporal detoxication method such as plasmapheresis in the
      complex treatment of acute intestinal ileus has been studied. 52 patients with
      acute intestinal ileus of various etiology were investigated. Clinical data such
      as nausea, vomiting, mouth dryness, body temperature, lessening of sounding of
      peristaltic or its absence, heart rate, short breath, presence of encephalopathy,
      lowering of diuresis, quantity of excretion at Miller-Ebbot sounding were used as
      the criteria of detoxication efficiency of plasmapheresis. For the estimation of
      efficiency of plasmapheresis by laboratory investigations the following data were
      determined: toxicity of blood plasma up to plasmapheresis and after carrying it
      according to the parametion test, leucocyte index, molecular composition of
      average blood mass. After plasmapheresis all indices of plasma toxicity had
      positive changes. Likewise positive changes were observed in clinical indices of
      intoxication. All the above stated enables us to evaluate plasmapheresis as a
      highly efficient method of extra-corporal detoxication, which may be successfully
      used during complex treatment of acute intestinal ileus.

PMID- 16980732
TI  - [On-pump versus off-pump coronary revascularization: early postoperative
      outcomes].
AB  - Postoperative results of CABG operations, performed with CPB or on beating heart
      (OPCAB) has been summarized. 200 cases have been reviewed. The patients were
      divided into two groups, depending on the type of the procedure. Results showed,
      that in the group of patients operated on beating heart there were no such
      complications as mortality, reexploration, neurological disorders. The percentage
      of complications like heart failure, intraoperative MI, postoperative
      arrhythmias, length of stay in ICU were considerably less comparing to the
      patients operated with CPB. Also cost-effectiveness of beating heart procedure vs
      traditional CABG has been documented.

PMID- 16980733
TI  - Role of suprapubic drainage in the transurethral resection of prostate (TUR-P).
AB  - We assessed some clinical parameters and biochemical changes during TUR-P under
      suprapubic trocar aspiration system with suction. 18 patients underwent TUR-P
      with active aspiration and other 17 using Iglesias type resectoscope. The mean
      values of Sodium, Potassium and hematocrite did not differ significantly between
      the groups before surgery and 20 minutes after the beginning of resection. At the
      end of surgical intervention changes in hematocrit values were insignificant and
      blood electrolyte showed marginal statistical difference. The mean time of
      operation and resection in study group was 45.38 min and 37.31 min respectively,
      and in control group 56.25 min and 47.83 min respectively. Average weight of
      resected prostate tissue in study group was 67.92 g versus 58.75 g in control
      group. The time needed for the resection of 1 g prostate in a study group was
      0.55 min versus 0.81 min in control group (p=0.05). The time needed for the
      removing of 1 g prostate tissue was 0.67 min and 0.96 min respectively (p<0.01).
      Our data supports that suprapubic trocar suction reduces the duration of the
      operation on the other hand, the mean time to remove one gram of prostate is much
      shorter comparing to conventional technique.

PMID- 16980734
TI  - Trabeculation of urinary bladder by ultrasound in patients with benign prostatic
      hyperplasia.
AB  - The aim of our study was to assess the prognostic value of trabeculation of
      urinary bladder assessed by ultrasound as an non-invasive diagnostic tool to
      diagnose the bladder outlet obstruction and prognostic factor to urinary
      retention and the need for surgery. Out of 171 patients 120 were with spontaneous
      voiding and other 51 were presented with acute urinary retention. 87 of them
      underwent surgical treatment immediately and other 17 underwent surgery during
      follow-up period 12 months. Ultrasound investigation revealed trabeculated
      bladder or with diverticula in 107 men and other 64 had non-trabeculated
      bladders. In 120 patients with spontaneous voiding 76 had moderate urinary
      symptoms (10 < I-PSS < 18) and other 46 had severe symptoms (18 < I-PSS < 35). 57
      patients had the residual urine volume les that 100 cc and 63 had above that
      amount. 50 patients had decrease peak flow below and other 70 had Qmax more than
      10 ml/sec. Using chi(2) test statistical analysis urinary symptoms and residual
      urine did not correlate with bladder trabeculation, though the low peak urinary
      flow Qmax highly correlated with bladder trabeculation (p<0.005). We observed
      high correlation between the bladder trabeculation and urinary retention
      (p<0.05); immediate indication for surgical treatment (p< 0.0001) and need for
      surgery during the one year follow-up (p<0.00019). Bladder Trabeculation may be
      helpful in differentiating between the compensated and decompensated stages of
      bladder outlet obstruction.

PMID- 16980735
TI  - Study of zinc content in blood serum of the patients with malignant tumors of the
      digestive systems.
AB  - Zinc (Zn)--the important atomavit (essential chemical element), which
      participates in 120 reactions proceeding in a living organism. There were been
      found the abnormal Zn-levels in blood in the cases of the various pathologies,
      including malignant tumors (MT) of the digestive systems. It has been determined
      the Zn-levels in the blood serum of 48 patients with MT of the digestive systems
      (nosologies: 24--MT of stomachs, 10--esophagus, 14--colorectum) and 12
      practically healthy persons. The results have been analyzed using binomial
      criteria (alpha=0.05; p<0.05). It has been found that in patients with MT of
      digestive systems increase or decrease of Zn-levels in the blood serum occurs
      with equal probability. That seems to reflect the peculiarities of functional
      disorders in mucous membranes, through which the Zn-absorption occurs.

PMID- 16980736
TI  - [The role of definition of receptor status in the prognosis and the choice of
      adequate treatment tactics of breast tumors].

PMID- 16980737
TI  - [Efficiency of treatment methods of the patients with small-cell lung carcinoma].
AB  - With the use of multivariational statistical analysis of 185 patients with small
      cell lung carcinoma has been established that median survival (in months), and 1
      year and 3-year survival rates (in percentage) of the patients are 9.4+/-2.6,
      41.6+/-2.4 and 41.6+/-2.4, respectively. Most of patients died within the year
      from clinical manifestation of the disease. It has been ascertained that
      individual treatment methods in many aspects define prognosis of the disease.
      After combined treatment (radio-chemotherapy) prognosis is better. 1-year
      survival rate in percentage is 58.6+/-4.8 in such cases, 3-year survival rate is
      equal to 12.3+/-7.2 and median survival is 11.2+/-4.7 months (p<0.05). It has
      been shown that of all chemotherapy schemes CDE (cisplatin, doxorubicin,
      etoposide) is more effective. 1-year and 3-year survival rates of the patients
      treated with the use of this scheme were statistically reliably better in
      comparison with those treated with the use of other chemotherapy schemes
      (p<0.05). Thus, at the resistance of a tumor to chemotherapy drugs and in case of
      development of a recurrent tumor, in order to reach complete remission or its
      consolidation it is reasonable to use combination of these preparations. Results
      of observation should be taken into account for the evaluation of the prognosis
      and the choice of most effective treatment method.

PMID- 16980738
TI  - [Treatment of malignant ovarian tumours in Georgia in 1990-2000].
AB  - The adequate treatment of ovary tumor and the issue of improvement of subsequent
      results still remain the urgent question of oncology. In 60-80% of diseased the
      pathology appears at the final--the third and the forth i.e. later stages, while
      the prolongation of life for the five years period is quite rare--13-47%. Our aim
      is to study the effectiveness of treatment of malignant ovary tumor based on the
      data of 1990-2000 provided by A. Gvamichava National Oncological Centre, to
      develop optimal methods of treatment and select the right tactics in order to
      improve subsequent results for patients with malignant ovary tumor. The research
      revealed that the epithelial neoplasm (malignant ovary tumor) is 5.2 times more
      spread than nonepithelial (malignant ovary tumor). In our clinic the preference
      is given to the operational method combined with further chemotherapy (ch/t) for
      treatment of malignant ovary tumor. The advantage is given to the radical surgery
      (59.4%), amputation of uterine appendages and omentum resection (79.3%). In the
      case of less radical surgery (23%)--amputation of uterine appendages (63.8%),
      while for non-radical surgery (17.5%)--ovariectomy, omentum resection (60%). The
      number of radical surgery of epithelial neoplasm 3 times exceeds less radical
      surgery and 12 times--non-radical surgery, while in the case of non epithelial
      neoplasm the number of radical surgery is two times more than less radical
      surgery and 3 times more than that non radical. In 1990-2000 in the National
      Oncological Centre ch/t without platinum and audrioblastin (44.8%) had been most
      frequently used for treatment of ovary tumor. The main schemes were:
      cyclophosphan + phtoruracyle and cyclophosphan + phtoruracyle +metotrexat.

PMID- 16980739
TI  - [Risk of the development of breast cancer during gynecological pathology].
AB  - Detection and timely treatment of diseases of the female's reproductive system,
      as one of the major risk-factors of the development of breast cancer, is one of
      the readily available and efficient methods of the prevention of the breast
      cancer in developing countries, including Georgia. Out results have shown that
      not only the fact of the existence of the gynecological pathology in the
      anamnesis, but also the duration of the pathology is a considerable risk-factor
      of breast diseases, including breast cancer. Realization of the reproductive
      function (pregnancy, number of birth and duration of the lactation period) in
      women can be evaluated as a major natural protector mechanism of the prophylactic
      treatment of breast diseases, including breast cancer.

PMID- 16980740
TI  - [Infectious causes of intrauterine fetal death].
AB  - We have done retrospective analysis of stillbirth. The aim of our study was to
      investigate specific role of infections in stillbirth on the basis of archival
      data of Acad. Chachava Research Institute of Perinatal Medicine, Obstetrics and
      Gynecology. In 768 cases of stillbirth over a period 2000-2004, in 591 cases
      occurred intrauterine fetal death (IFD) (77%). In 85% of cases it was related to
      the preterm labor. Most frequently IFD occurred in relation to the congenital
      fetal malformations (24.4%). In 12.1% of cases the cause of the structural
      anomalies in fetuses was unknown. Infectious pathology occurred in 17.1% of cases
      and in 15.4%--preeclampsia. Significantly high percent are related to the unknown
      reasons that lead to the IFD (34.3%). Study addressing the risk factors of the
      intrauterine fetal death IFD revealed that odds ratio (OR) is the most high for
      fetal malformation--36.34; for preeclampsia--5.15; for infectious pathology-
      10.93; so it holds the third place after the fetal maldevelopment and
      preeclampsia.

PMID- 16980741
TI  - [Benefits of antioxidant agents' use for dental filling consequent to the endo
      bleaching].
AB  - Efficacy of antioxidant agents' use after dental endo bleaching was studied in
      clinical trial. The study enrolled 169 patients, ranging age 16 to 60 years in
      age. The patients were randomized into 2 groups: control (63) and trial (106). In
      patients of the control group tooth cavity was left open after endo bleaching,
      and was filled only after 7 days. In patients of the trial group antioxidant
      agent was administered into the dental tissues consequently to the endo
      bleaching, and the cavity was filled immediately. Assessment of the immediate and
      distant effects revealed unwanted results of postponed dental filling (control
      group) in terms of tooth color stability and forming micro cracks. Results of
      antioxidant use and immediate dental filling after endo bleaching have proven our
      earlier experimental studies on benefits of antioxidant use to be right. Based on
      the results of our clinical study we can recommend use of antioxidant after endo
      bleaching to achieve successful dental fillings in clinical practice.

PMID- 16980742
TI  - [Influence of treatment of vanadium electrophoresis on certainbio-chemical and
      immunological indicators in patients with prolonged cases of pneumonia].
AB  - Inflammatory process in bronchial and lung tissues during the prolonged cases of
      pneumonia causes failure of immunological system and depression of glucocorticoid
      and androgenic functions of cortex of kidneys. That's why it's important to find
      new, more effective anti-inflammation means causing reduction and even
      disappearance of inflammatory process in bronchi and lungs, influencing
      immunological system positively and normalizing its condition and cortex of
      kidneys. 65 patients of age from 25 till 64 were examined, from which 31 had
      nidal prolonged pneumonia and 39 had interstitial prolonged pneumonia. It was
      stated that treatment with vanadium electrophoresis causes reduction and even
      disappearance of the inflammatory process in bronchi and lungs in the patients
      with prolonged pneumonia, leading to the strengthening of cellular chain of the
      immunity, nonspecific resistance of the organism, has a desensitisation
      influence, strengthens glucorticoid and androgenic functions of cortex of
      kidneys, normalises interchange of proteins and humoral immunity, increased
      substance (contents) of vanadium in the whole blood. Indicated positive results
      were more significant in the cases of nidal prolonged pneumonia.

PMID- 16980743
TI  - [Effect of treatment with selenium electrophoresis on biochemical indices in
      patients suffering from ischaemic cardiac disease with a stable stenocardia of
      tension].
AB  - Disturbances in lipid metabolism, intensification of lipid peroxidize oxidation
      and functions of sympatho-adrenal system play an important role in the
      development and progressing of ischaemic cardiac disease. As a result of
      investigations it has been established that microelement--selenium has an
      antiatherogenic action and suppresses peroxidize oxidation of lipids. The effect
      of treatment with selenium electrophoresis in patients suffering from ischaemic
      cardiac disease with a stable stenocardia of tension has been studied. Total of
      76 patients with ICS:SST of I-II functional classes (FC) have been investigated.
      It has been established that treatment with selenium electrophoresis provokes a
      reduction of overall cholesterol, triglycerides and beta-lipoproteins content in
      blood serum, as well as a decrease of cholesterol amount in beta-lipoproteins,
      lipoproteins of low and very low density and diene conjugates in blood serum and
      adrenaline and norepinephrine excretion with urine; increase of lipoprotein
      amount of high density in blood serum, activity of catalase and selenium
      excretion with urine. Above-said positive changes in biochemical data were more
      pronounced for the ICS:SST of the first FC.

PMID- 16980744
TI  - [Chromosomal instability of peripheral blood lymphocytes in patients with
      precancer gastric cases].
AB  - Results of clinical and instrumental-laboratory study of 17 cases are presented.
      According to the rapid urease test (CLO) and histological studies, the
      helicobacter infection was found in 12 (70.6%) cases out of the group of 17
      suffering from chronic atrophic gastritis, gastric ulcer adenomatous polyposis.
      Analyses of Helicobacter pylori dissemination over the gastric mucosa manifested
      the I (weak) degree (up to 20 microbes within field of vision) prevailing in 8
      (66.7%) of 12 cases, while the II (medium) degree (up to 50 microbes within field
      of vision) and III (high) degree (over 50 microbes within field of vision)
      occurred only in 4 cases (33.3%). By comparative cytogenetic research of the
      peripheral blood lymphocytes we found the immunogenetic markers and
      characteristic features of cytogenetic disturbances in the immunocompetent cells
      in cases of pre-cancer Helicobacter pylori-associated diseases (chronic atrophic
      gastritis, gastric ulcer, adenomatous polyposis). Statistical data confirmed an
      increase in the percentage of cells with chromosomal aberrations, which amounted
      to 4.25+/-0.51 in the chronic atrophic gastritis cases, 3.5+/-0.46 in the gastric
      ulcer cases, 5.75+/-0.60 in the adenomatous polyposis cases for 100 analyzed
      metaphases. Considering the questionable role of Helicobacter pylori as a direct
      initiator of mutagenesis, the immune disturbances may be caused by the damage of
      DNA of lymphocytes resulting from the genotoxic effect of some intermediates of
      inflammation.

PMID- 16980745
TI  - [Clinical features of cannabis psychosis in schizophrenia patients].
AB  - Available information regarding the clinical features of cannabis-induced
      psychoses among schizophrenia patients is rather odd and even discrepant. For
      thorough investigation psychopathology due to marijuana intoxication, we examine
      two groups of schizophrenia patients. I group--14 patients, who had long history
      of cannabis use before developing schizophrenia, and II group--schizophrenic
      patients, who already had schizophrenia and later became marijuana users.
      Clinical study allowed us to determine the general psychopathological symptoms
      due to acute intoxication on the one hand, reflecting duration and severity of
      intoxication, and let us to verify specific mental problems connected to the
      dynamics of schizophrenia, on the other hand. Peculiar properties of the data of
      the experimental-psychological tests TAT (Thematic Apperception Test) reflect
      personality changes generated by schizophrenia progression included the
      psychopathological phenomenon related to cannabis intoxication.
      Psychopharmacological treatment brought positive changes in structure and
      thematic features of the data. The patients used more words. The content and the
      volume of the stories increased. Trends to improvement were more common for
      recurrent rather than continuous duration of schizophrenia.

PMID- 16980746
TI  - [Neuropsychic infringements and problem behaviour of teenagers].
AB  - Disorders of neuropsychic functioning play a greater role during formation of
      problem behaviour. Researches specify frequency of disorders of verbal skills and
      skills of self-checking in group of teenagers with problem behaviour. Difficult
      teenagers differ by greater expressiveness of insufficiency of some intellectual
      operations, such as ability to generalization, verbal memory, arithmetic
      operations. Researches of nonverbal intelligence have revealed much more low
      parameters in group of delinquent teenagers in comparison with control group. It
      is considered, that verbal insufficiency has indirect influence on antisocial
      behaviour through school progress.

PMID- 16980747
TI  - Ifn/Rbv treatment induced anemia and its correction with epoetin alpha in
      patients with hepatitis C.
AB  - The aim of the 18 months follow up study was to assess the frequency of anemia
      during IFN/RBV therapy in patients with chronic hepatitis C; to manage anemia
      either with recombinant human erythropoietin (rHuEPO)--epoetin alpha or with RBV
      dose reduction and to compare the rate of SVR in patients with RBV dose reduction
      and with administration of epoetin alpha. Study enrolled 61 patients with chronic
      active hepatitis C aged 33-61 years. All patients had HCV genotype 1b. Out of
      them 41 were male and 20 female. Anemia (Hb <10 or >2 g/dL Hgb drop from
      baseline) developed in 41 patients out of 61 (67,21%) during the therapy. These
      41 patients were randomized into two groups: 21 patients who received 40 000 IU
      epoetin alpha weekly (I group) and 20 patients in whom for managing anemia we
      used standard of care (SOC) or RBV dose reductions from 1000/1200 to 800/600 mg
      (II group). In all 21 patients of the I group the Hb level normalized without
      reduction of RBV dose. In this group of patients SVR at 6 months after completion
      of full course of treatment was achieved in 17 (66%) patients. Improvement of
      quality of life (QOL) was observed in all 21 patients. Out of 20 patients of II
      group with standard of care (SOC) 5 patients developed symptomatic anemia with
      fatigue and dyspnoea; RBV was stopped temporarily. In 15 patients RBV dose was
      reduced from 1200 mg to 600 mg for correction of anemia. In this group of
      patients SVR at 6 months after treatment completion was achieved in 7 (25%)
      patients. Lower RBV doses yield a lower treatment response in patients with HCV
      genotype 1. In anemic HCV-infected patients on RBV/PEG-IFN therapy, EPO maintains
      RBV dose and significantly improves anemia and QOL. EPO has the potential to
      improve adherence rate, which may in turn improve SVR.

PMID- 16980748
TI  - [Muscle strength and mobility of nerve processes among women judoists taking into
      account their menstrual cycle].
AB  - The problem of female sports is considered foremost importance and attract vivid
      attention of scientists and coaches as well. This problem requires special
      research in order to establish effective means for high sportive achievements by
      the sports women, however, without deteriorating their health. Analysis of the
      obtained results showed that physical characteristics were changed in the process
      of permanent training. Sports women's loading should be increased step-by-step,
      in accordance with the level of functional possibilities and menstrual period. In
      1,3 and 5 phases of menstrual cycle, physical activities have to be optimal and
      during the systematic exercises well answer supportive effect and in 2,4
      menstrual cycles, the physical exercises may be maximal. Correct allocation of
      exercises activities considering the menstrual cycle gives the trainer
      possibility to train the sportsmen and enhance the sport effect.

PMID- 16980749
TI  - [The role of some pituitary hormones in patients with non-insulin-dependent
      diabetes mellitus and diabetic retinopathy].
AB  - The level of somatotropin and thyreotropin hormones was measured in blood plasma
      of patients with non-insulin-dependent diabetes mellitus with and without
      diabetic retinopathy (DR). Fifty eight patients (26 males and 32 females) aged
      from 35 to 75 were examined. The patients were divided into two groups. First
      group included 29 patients (13 males and 16 females) with non-insulin-dependent
      diabetes mellitus without DR. Second group included the same number of patients
      with non-insulin-dependent diabetes mellitus complicated by DR. The concentration
      of somatotropin hormones was increased and thyreotropin was decreased in patients
      with non-insulin-dependent diabetes mellitus with DR. The results suggest that
      somatotropin and thyreotropin contributes to the development of diabetic
      retinopathy in humans.

PMID- 16980750
TI  - [The assessment of risk factors of the atresia of the gastro-intestinal tract].
AB  - The rate of gastro-intestinal tract atresia is around 0.3 percent in Georgia. In
      common cases delayed surgical treatment of these malformations is the reason of
      perinatal mortality. So, it is very important to concretize the risk factors,
      which cause the development of gastro-intestinal tract atresia. Our research was
      performed on the basis of examination of 161 probands with Gastro-Intestinal
      tract atresia and 155 control probands from the common population of Georgia, and
      also their relatives of I, II, III degrees of kinship. The methods of
      investigation were: clinical, paraclinical, genealogical, genetical
      epidemiological. The analysis of the clinical material was done by the multiple
      statistical method with the alternative analysis. It was shown, that an elderly
      age of parents, spontaneous abortions, or a hazard of spontaneous abortions,
      acute infections, emotional stress and the action of other teratogenic factors
      during the I trimester of pregnancy, hormonal misbalance of mother and some of
      the professional factors (especially agricultural) are most important etiologic
      and pathogenetic factors of the gastro-intestinal tract atresia.

PMID- 16980751
TI  - [Oxidative metabolism parameters in newborns with sepsis during the cerebral
      ischemia of different degrees].
AB  - Within the last decade neonatal sepsis remains one of the actual problems of
      medicine due to its high morbidity and lethality rates. Reference data clarify
      that in septicaemia pathogenesis a great importance is attributed to the cellular
      oxidation-reduction imbalance and oxide stress development. A redox imbalance
      developed during sepsis indicates to the cell's dysfunction. Also central nervous
      system is one of the first organs, which is damaged during the sepsis. The
      purpose of our research was the investigation of activity of pro- and antioxidant
      system in newborn babies with sepsis during the cerebral ischemia of different
      degrees. It was shown that during the newborns' sepsis the intensity of free
      radical oxidation-reduction process was increased remarkably, antioxidant system
      activity decreased and intensive ESR-signal of HbNO MetHb was fixed in the blood.
      These changes caused to development of hypoxemia and deep cerebral ischemia.

PMID- 16980752
TI  - [State of health of children and structure of morbidity in the region of
      catastrophe of oil producing plant].
AB  - On September 9, 2004 in Sagarejo region, Ninotsminda village an ecologic
      catastrophe took place. As a result of explosion at the oil-producing plant there
      was an oil spill in the surrounding soil, which caused the pollution of the
      environment. Among children living in Ninotsminda village (the main zone) 370
      children were investigated for evaluation of the state of their health and
      nosological structure of the morbidity. The observation was performed by stages.
      1st stage: study of the zone 1 year before the catastrophe. 2(nc) stage:
      quarterly dynamic control over the state of health of the children in both zones
      for the purpose of comparison of definition of the absolute number of morbidity
      index. It was found that after the catastrophe the absolute number of diseases in
      the main zone increased 10.8 times, and in the control one significant
      alterations did not appear. According to the nosological structure of the
      morbidity the predominance of pathology of pulmonary-respiratory system was
      revealed.

PMID- 16980753
TI  - ISAAC I and III in Georgia: time trends in prevalence of asthma and allergies.
AB  - ISAAC I and III surveys were carried out in schoolchildren aged 6-7 years from
      two centres of Georgia to estimate time trends and geographic variations in the
      prevalence of asthma, rhino-conjunctivitis and atopic eczema symptoms. A standard
      core questionnaire was used following the ISAAC methodology and was completed by
      the schoolchildren's parents. The prevalence of symptoms of allergic diseases in
      Phase I and Phase III was compared. The average prevalence of "current wheezing"
      almost not changed over 7 years, however there was some heterogeneity across the
      centres, particularly in Tbilisi centre the prevalence of current wheezing
      increased by 2.6% and in Kutaisi (it decreased by 2.4%. The symptoms of current
      rhino-conjunctivitis slightly decreased, but not statistically significant. More
      significant reduction was observed for symptoms atopic eczema, which was revealed
      in both centres. The results indicate that the epidemiological features of asthma
      and allergies in Georgia are changing, although the causes are still uncertain.
      Different patterns of time trends between centres suggested that there may be
      local differences in risk factors.

PMID- 16980754
TI  - Social isolation rearing of rats decreases the nervous system's resistance to the
      psychogenic stress stimuli.
AB  - Established that one of the factors promoting development of the psycho-nervous
      diseases, are various kinds of social deprivation. The purpose of this study was
      investigation of importance of social interactions at the early period of
      postnatal in development of resistance of the nervous system against the
      psychogenic stress in the adult rats. At weaning, male albino outbred rats from
      three litters were housed socially (control rats) (n=12) or in isolation (n=14)
      for 8 weeks. Modeling the psychogenic stress was performed with the modified
      active avoidance response method. Judging by the speed of acquisition of the
      active avoidance response, i.e. the learning speed, the isolated rats
      significantly lagged behind the control animals. Behavioral acts in the control
      animals manifested with different duration and ratio, depending on the complexity
      of the task and situation, which should point at differential activities of the
      self-regulatory mechanisms, at different stages of psychogenic stress. In all
      situations: in acquisition-stabilization of the active avoidance responses and in
      conditions of the 14-days stressing, behavior of the isolated animals did not
      change and the horizontal standings were dominating, while the vertical standings
      and grooming were poorly displayed. Thus, the isolated rats are characterized
      with insufficient development of the self-regulatory mechanisms of the brain.
      Therefore, social deprivation decreases the nervous system's resistance to the
      stressogenic stimuli.

PMID- 16980755
TI  - Flow cytometry and immunomorphological characteristics of apoptosis in
      hepatocytes of white mice during aging.
AB  - Apoptosis, sometimes called "programmed cell death", the process that goes on
      continuously throughout life has received phenomenal attention in the past few
      years. In the process of aging of organism, most of organs undergo morphological
      and functional changes at various frequencies. Initially, the role of apoptosis
      regarding aging was evaluated negatively, however, at present the issue is in the
      process of reconsideration. The experiments were performed on 74 white mice,
      distributed in three age groups (juveniles, adults, and senescents). Apoptotic
      nuclei were detected by immunomorphological and flow cytometry assay. So, the
      analysis of the data obtained that apoptosis in hepatocytes of white mice
      decreases with age and afterwards increases in a credible way. The maximum value
      is reached in the senescent mice. It has been considered, that aging increases
      the susceptibility of hepatocytes to apoptosis in white mice.

PMID- 16980756
TI  - [The reaction of monoamines and sex hormones on vibration pathology and
      correction of this pathology with anabolic steroids].
AB  - The experiment was held on two groups of 40 grown-up white male rats. After the
      tests had bean finished by means of high-performance liquid chromatography method
      the quantity of monoamines (norepinephrine, serotonin and dopamine) was defined
      in hypothalamus, and the concentration of sex hormones (Follicle stimulating-
      FSH, Luteinizing hormone--LH, testosterone--T, estradiol--E(2)) was also defined
      by immunoferment method in the blood. The research showed that in both groups
      serotonin's level increased compared with the control group. In the first group
      its concentration increased to 147% and in the second one to 120%. As the rate of
      norepinephrine in the first group was increased by 41% against the background of
      anabolic steroid- -retabolil injections its concentration reduced to 90%. Its
      especially worth mentioning that as in the first case the concentration of
      dopamine was too reduced to 14% in the second case it made 70%. As a result of
      the research it was established that the concentration as T and E(2) as their
      regulator gonadotrophin hormones were decreased in the first group, but in
      condition of vibration pathology's correction with retabolil the rate of FSH and
      LH were within the norm, it follows that the rate of sexual steroids T and E(2)
      were within the norm.

PMID- 16980757
TI  - [Serological method of rapid identification of antibodies against fungi of
      Candida genus].
AB  - Technology of preparation of antigenic erythrocytes diagnosticum for detection of
      antibodies against fungi of Candida genus in humans blood is presented.
      Preparation is used in reaction of passive haemagglutination destined for
      serological investigation of candidosis. Erythrocytes of sheep treated with
      formalin and tannin acid were used for preparation of diagnosticum. In the
      capacity of sensitin were water-soluble antigens, received by multiple (5-6)
      freezing-wash cleaning of Candida fungi cultures. Optimal sensitizing dose (8
      mkg/ml) was defined experimentally. Investigation of blood serum of healthy
      people has shown, that medium titer of anti-candidosis antibodies is 38.0+/-7.9.
      Obtained results testify, that antigenic diagnosticum could be successfully used
      for serological diagnosis of diseases caused by fungus of Candida genus.

PMID- 16980758
TI  - [Change of concentration of L-carnitine in blood and other tissues in rats on a
      background of the alcohol intake and influence of mildronate on its level].
AB  - Mildronate is an antiischemic drug. It inhibits carnitine biosynthesis
      (suppresses beta-oxidation of fatty acid) The aim of the study was to establish
      how Mildronate influences the concentration of L-carnitine in blood and in some
      tissues in rats with various stages chronic consumption of alcohol. 28 white rats
      instead of drinking water were taking 15 % ethanol. In the group A the rats were
      on the three-week alcohol consumption, in the group B--after 3 weeks of alcohol
      consumption on a background of alcohol they were taking the mildronate, group C-
      four-week alcohol consumption; D--after 4 weeks of alcohol consumption only
      mildronate was administered. The concentration of L-carnitine in the group A was
      as follows: in the liver 136.11+/-2.44; in heart 74.3+/-3.15; in brain 60.44+/
      5.21; in blood 45.8+/-2.32. In the group B: in liver 115.7+/-4.69; in heart
      72.11+/-4.23; in brain 59.23+/-2.44; in blood 62.5+/-1.99. In the group C: in
      liver 107.71+/-1.43; in heart 52.57+/-0.95; in brain 71.5+/-1.08; in blood 38.8+/
      2.32. And in group D: in liver 106.94+/-1.81; in heart 42.04+/-0.88; in brain
      56.84+/-2.75; in blood 2.37+/-0.69 (nmol/l). During the chronic use of alcohol
      the decrease of concentration of L-carnitine is marked. The level of L-carnitine
      is reduced under influence of alcohol, but at the same time it suppressed also
      all steps of metabolism of the cells. Mildronate not only suppresses carnitine
      dependent oxidation, but also switches metabolism to more favorable aerobic
      glycolysis. Under the influence of mildronate general condition of the body is
      improved both during complete acceptance of alcohol, and on the background of
      continuation of consumption of alcohol.

PMID- 16980759
TI  - State of hypophsis-adrenal gland in conditions of vibration pathology and its
      correction in experiment.
AB  - Vibration is one of the pathological factors, which causes various alterations in
      the cells and organs. The goal of the research was the investigation of the
      hypophysis-adrenal gland system during the vibration and possible methods of its
      correction. The experiment was held on 70 grown-up male rats from 180 to 200 gr
      in weight. An hour vibroseance was carried out daily during two months period.
      According to the means of treatment animals were divided into three groups. The
      control group was consisted of 10 animals. In the first group (experimental
      vibratory pathology without any therapy) concentration of AKTH began to increase
      and reached 154% by the 20th day; by the 40th day it was 130%; AKTH concentration
      decreased up to 87% by the 60th day. The corticosterone in the blood plasma
      increased gradually and by the 20th day reached approximately 188%, which by the
      40th day gradually decreased to 156%, and by the 60th day it was 129%. The second
      group was composed of animals, which underwent liquid oxygen therapy after the
      vibroseance. The AKTH content in the blood plasma of the second group animals was
      less increased: by the 20th day it reached 134%, by the 40th day it was 117%, and
      by the 60th day it decreased to 84%. The corticosterone concentration in the
      second group was lower by the 20th day it was 168%; by the 40th day it reached
      approximately 143%, and by the 60th day decreased to 127%. The third group was
      composed of retabolil treated animals. The AKTH concentration in animals by the
      20th day reached 206%, and then decreased gradually, and by the 40th day it was
      189%, and by the 60th day decreased to 145%. The corticosterone content in the
      blood plasma was high. By the 20th day the concentration was 263%, then it
      gradually decreased and by the 40th day reached 242%, and by the 60th day it was
      199%. According to the experimental data vibration leads to the activation of
      hypophysis-adrenal gland system. Increased AKTH initiated increase of
      corticosterone.

PMID- 16980760
TI  - [Alterations of gonadal axis and sexual steroids concentration in the conditions
      of intoxication with phenol in the experiments].
AB  - It is known that the male reproduction system is too sensitive to the impact of
      the environment conditions. One of such endocrine deregulators is phenol. The
      experiment was held on the 40 adult male albino rats of the mass 200-250 g. Each
      animal during 15 days was daily experienced intoxication with phenol in the
      special closed cabin. On the 16th, 30th, 45th and 60th days after the initiation
      of the experiment we performed decapitation of the animals in conditions of
      general anesthetic, after what in the blood serum we defined alteration of the
      concentration of gonadotrope hormones LH, FSH and sexual steroids--testosterone,
      estrone, estradiol, by means of immune-enzyme method. During the experiment the
      significant alterations of hormones concentration were revealed, namely, in the
      mentioned research it was revealed that LH did not stimulate the testosterone
      secretion, conversely it decreased, while the estrogen concentration increased.
      The mentioned data gave us basis to conclude that the impact of the phenol vapor
      caused disorder of the male reproduction function.

PMID- 16980761
TI  - [Efficiency of assessment of retinol, alpha-tocopherol and beta-carotene by the
      liquid chromatography method].
AB  - Benign prostatic hyperplasia is very frequent disease of the primogenital system
      of elderly men. As the investigations show the antioxidant vitamins have various
      influence on the men's organism. They participate in the pathogenesis of many
      diseases. Taking into account all these circumstances, the prophylactic problem
      must be solved according to the foreseen provision of organism with the vitamins.
      It is very important to have the appropriate methods for determination of
      vitamins and their provitamins. Nowadays, to determine vitamin A, its form b
      carotene and vitamin E, a High Pressure Liquid chromatography is used. We have
      developed an original, highly sensitive method of determining retinol, alpha
      tocopherol and b-carotene, which is characterised by simplicity and high
      accuracy. Applying this method to the determination of vitamins concentration in
      10 healthy donor's blood gave the following results: for the Vitamin A 567.99+/
      57.49345 mkg/l , Vit. E-16.133+/-0.33941 mkg/l and b-carotene- 0.8621+/-0.810
      mkg/l. This corresponds to the reference data. It is suggested that it is
      possible to use above-mentioned method for routine epidemiological
      investigations.

PMID- 16980762
TI  - [Radio-hygienic safety of personnel performing endoscopic investigations].
AB  - The work presents radio-hygienic characteristics for work regimes of medical
      personnel engaged in complex X-ray endoscopic investigations. Irradiation dose
      levels of medical personnel have been defined depending on roentgen diagnostic
      stand constructions. In endoscope regimes X-ray irradiation dose rate averages
      from 80 to 255 mr/h for an endoscopes and from 14 to 80 mr/h for a nurse. Local
      irradiation dose levels for specialists who are working with the endoscope
      retrograde pancreatocholegraphy have been measured. Irradiation dose rate for an
      endoscopies with an individual dose meters fixed on a Shielding apron surface
      ranges from 1.5 to 14.7 mr/h for single investigation and for a nurse from 1.0 to
      4.0 mr/h.

PMID- 16980763
TI  - [Comparative analysis of the influence of various factors in different
      combinations on the ionic homeostasis of a cell].
AB  - The ionic homeostasis is one of the most sensitive tests for the evaluation of
      functional state of a cell. The agents, which promote elevation of ionic
      homeostasis, as well as those, which suppress it, are well known. The goal of the
      present work was tracing the possibilities for altering ionic homeostasis into
      one or another direction, as a result of combined influence of some agents:
      ionizing radiation at a dose of 0.1 Gy, EMF with frequency of 45 Hz, 2.0 mT, in
      one case, and addition to this combination of the homeopathic remedy--stimulated
      phosphoric acid, at different dilutions. The following data have been obtained:
      combination of ionizing radiation of 0.1 Gy increased effect against the effect
      of its constituents, while addition of phosphoric acid at dilution of 10(-14)
      increased effect even further. In the other series of experiments, combination of
      ionizing radiation of 0.5 Gy and EMF was used in the same conditions; as a
      result, the sum effect decreased against its constituents, while addition of
      highly diluted (10(-200)) phosphoric acid practically arrested this effect. It is
      concluded that effect of a combined influence depends on a dose of the
      constituents.

PMID- 16980764
TI  - [Evaluation of anti-blastoma effects of tetravaccine in combination with
      chemotherapy].
AB  - The present work discusses methods of immune-correction and immune-rehabilitation
      of oncological patients using specific bacterial polyvalent vaccines. With this
      purpose the tetra-vaccine (Staphilococcus-Proteus-Clepsiela-Escherichia) has been
      used. Experiments have been carried out on white rats and mice with Sarcoma C-45.
      For chemotherapy of malignant tumors the following remedies were used:
      Cyclophosphan, Vincristin and Adriablastin. The vaccine and chemotherapy were
      applied in both ways, separately (control), and in combination. The results of
      investigations have shown that the best effect was achieved in case of
      combination of vaccine with chemotherapy--particularly, in the first experimental
      series malignant tumors completely underwent regression, while using only tetra
      vaccine, the percent of malignant tumor growth inhibition constituted only 37.6%,
      and in the second experimental series percent of tumor growth inhibition
      constituted 56%-100% and the life span was prolonged by 22.4%-54.6%. Thus, the
      received results are quite encouraging and suggested method could be used for
      treatment of patients with cancer.

PMID- 16980765
TI  - [Analysis of results of certification of bacteriologists in Georgia and the ways
      of its optimization].
AB  - Analysis of the certification of bacteriologists in Georgia (234 specialists) has
      shown that 164 specialists (90-100%) passed the certificate examination with high
      and excellent scores. It indicates to the importance of expansion of test
      questionnaires as well as their complication by 8.8%-9.4%. Specialists with low,
      average and good progress in studies showed almost the same scores (75-80%). All
      together it makes 26% of those who did not pass the examination. According to
      subjects, most specialists make mistakes in general microbiology, especially in
      morphology and physiology of microbes, practical skills, there are a lot of
      mistakes in special microbiology, especially in diagnostics of infections caused
      by anaerobes and hemofil. Most specialists poorly managed questions in
      immunology, clinical microbiology and quality of laboratory researchers. Our data
      should be important for the further adaptation and modernization of certificate
      test-questionnaires.

PMID- 16980766
TI  - [Wounds treatment by the transplantation of the fibroblasts and stem cells on
      collagenic matrix].
AB  - During many decades the development of effective methods of wounds treatment has
      been and still remains to be one of the most actual problems of surgery. Interest
      and constant attention to wounds speaks first of all that simultaneously with
      development of medicine, cellular and molecular biology, molecular genetics and
      immunology consideration of wounds processing is constantly vary. New prospects
      and opportunities of effective treatment of wounds are opening. We develop a new
      original method of treatment full-thickness wounds by a method of transplantation
      fibroblasts and stem cells on the basis of collagenic matrix. The presented
      method of treatment of full-thickness wounds provides the most perfect
      realization of stimulating action of cultures of cells on the processes of
      regeneration of tissue. Application of fibroblasts and stem cells on the basis of
      collagenic matrix promotes restoration of normal structure of a skin and allows
      reducing terms of healing considerably. Stem cells are integrated into three
      dimensional tissue structures of an organism and promote histotopically to
      restoration of defects of a skin covering. Here it is necessary to note, that
      transplanted skin fibroblasts synthesize and allocate in an environment a plenty
      of biologically active substances among which distinguish epidermal growth factor
      (EGF), fibroblast growth factor (FGF), transforming growth factor (TGF),
      keratinocyte growth factor (KGF), and also various components of extracellular
      matrix.

PMID- 16980767
TI  - Is endogenous opioid system involved in non-opioid analgesics tolerance?
AB  - Recent investigations using metamizol and lysine-acetylsalicylate have shown that
      these non-opioid analgesics produce central anti-nociceptive effects probably
      through neural substrates that also support the analgesic effects of opiates. The
      aim of this study was to examine whether a clinically relevant approach, e.g.
      systemic administration of analgine, ketorolac and xefocam causes tolerance to
      them, and cross-tolerance to morphine. The experiments were carried out on
      experimental and control rats with saline by the model of tail-flick reflex to
      the stimulation of focusing light. Latency increase of this reflex indicates the
      degree of antinociception. This study of non-opioid analgesic effects on the
      latency of tail-flick reflex in rats has shown that systemic injections of
      analgine, ketorolac and xefocam result in significant antinociception as compared
      with the control group of rats with saline. Repeated administrations of these
      drugs revealed tolerance to them and cross-tolerance to morphine. Intraperitoneal
      injections of naloxone did not significantly decrease the morphine analgesic
      effect in analgine- and ketorolac-tolerant rats, whereas in saline-treated
      animals morphine analgesic effect was reverted. Taken together the present and
      previous findings support the notion that the contribution of the CNS,
      particularly of downstream pain-control structures, to the analgesic effects of
      NSAIDs involves endogenous opioidergic mechanisms. Thus, obtained data support
      the suggestion about a close relation between non-opioid tolerance and endogenous
      opioid system.

PMID- 16980768
TI  - [Does there exist one specific "view of man" in naturopathy / complementary
      medicine?].
AB  - BACKGROUND: Practitioners and users of naturopathic therapies claim that one of
      the assumptions underlying their work is a holistic "view of man". OBJECTIVE:
      Does there exist one specific view of man in present naturopathy and what does
      this mean? MATERIAL AND METHODS: Database and literature research of use and
      meaning of the term "view of man" and descriptive analysis. RESULTS: The term
      "view of man" is neither timeless nor related to a specific subject area. Its
      meaning is connected with the state of knowledge of the respective epoch as well
      as its reception in science and society. The discourse concerning the term "view
      of man" in the 2nd half of the 20th century in German literature shows, that in
      different fields the argumentation about one specific view of man shifts towards
      a pluralistic understanding of man. This pluralistic view about man exists in
      medicine as well. On the one hand conventional medicine, a long time under
      influence of the reductionism of natural science, has widened its worldview due
      to methods and questions of different disciplines such as psychosomatics,
      psychotherapy or social medicine towards a more complex perception of man. On the
      other hand Traditional European Naturopathy (TEN) too, claims to respect aspects
      of the "body-mind-soul-unity" in its understanding of man; yet, in connection
      with its hardly ever explained "natural forces". Besides the findings in
      literature clinical experience with our patients reveals some aspects that are
      characteristic of today's pluralistic naturopathic understanding of man and could
      also be useful for conventional medicine: recognition of patients' expectations
      (e.g. subjective view of illness), participation in the therapy planning (e.g.
      construction of how to get healthy) and naturopathic modes of therapy (e.g. start
      of therapy at healthy parts of the body, too). CONCLUSIONS: Despite some
      characteristics in naturopathy one finds variations of views or images of man,
      which originate from multiple subjective and socio-cultural perspectives of
      patients and therapists and which require, next to medical knowledge, on both
      sides openness and communication regarding aspects of health, illness and
      therapeutic settings.

PMID- 16980769
TI  - [Associations between chronic irritation of tonsils, indurations of connective
      tissue areas and brachialgia paresthetica nocturna].
AB  - Projective and reflex zones of inner organs to the body's surface are well
      described but there are only few clinical studies about abnormal zones.
      OBJECTIVE: The aim of our study was to investigate associations between chronic
      irritation of tonsils, abnormalities of the connective tissue areas over the
      musculus trapezius and the severity of brachialgia paresthetica nocturna.
      METHODS: Cross sectional study in 100 adult pain patients from an outpatient pain
      department. Patients with tonsillectomy were excluded. Examinations of tonsils
      and the connective tissue area were done separately by two mutually blinded
      physicians. Both were also blinded to the patients' evaluation of his/her
      brachialgia. RESULTS: Regardless of the lateralization, the severity of the
      tonsil irritations was correlated with the abnormalities of the connective tissue
      areas (Spearman's rho = 0.82; 95% confidence interval (CI): 0.74-0.87; p < 0.001)
      and the severity of the brachialgia (rho = 0.64, CI: 0.50-0.74; p < 0.001),
      furthermore indurations of connective tissue areas correlated with the severity
      of brachialgia homolaterally (rho = 0.57; CI: 0.42-0.69; p < 0.001). These
      correlations are considerably higher than those of other connective tissue areas.
      CONCLUSIONS: The results support the existence of easy to diagnose reflex zones,
      at least in a highly selected population of pain patients. They can give
      plausible hints for naturopathic treatments of brachialgia paresthetica nocturna,
      i.e. treatment of the relevant connective tissue zone above the M. trapezius.

PMID- 16980770
TI  - [A new sensor technique for measurements of electrical potential profiles of
      human skin at acupuncture points].
AB  - From an electro-physiological point of view human skin shows an inhomogeneous
      pattern regarding its electrical resistance: in certain areas a decreased
      electrical resistance can be observed. It has been postulated that these areas
      correspond to acupuncture points. Subsequently, devices have been developed as
      detectors for acupuncture points which are used for diagnosis and treatment in
      acupuncture. However, most of these devices are inconsistent: they show a
      remarkable inaccuracy in their measurements and are poorly evaluated. Further
      analyses have shown that the measuring pens often used are subject to various
      disturbances such as pressure, angle of measurement, humidity of the skin,
      different thickness of stratum corneum of the skin and external disturbances such
      as temperature and humidity in the measuring room. MATERIAL AND METHODS: We
      present a new device for standardized measuring of electrical skin resistance. It
      consists of a field of 64 electrodes (measuring array) on a surface of 60 x 60
      mm(2) and a distance of 8 mm between electrodes. For a more precise spatial
      resolution a field of 32 electrodes on a surface of 3.5 x 3.5 mm(2) with a
      distance of 0.65 mm is available. A high, precise, temporal resolution of
      electric potentials in human skin is realized by fast scanning of the electrodes.
      Technical details are described. CONCLUSIONS: First analyses of collected data
      show that reliable and valid measurements are possible. Using this device in a
      controlled and blinded study design will help elucidate the issue of altered skin
      resistance at acupuncture points and clarify if this phenomenon is unique at
      acupuncture points.

PMID- 16980771
TI  - Complementary and conventional medicine in Switzerland: comparing characteristics
      of general practitioners.
AB  - OBJECTIVES: Do structural characteristics of general practitioners (GPs) who
      practice complementary medicine (CAM) differ from those GPs who do not? Assessed
      characteristics included experience and professional integration of general
      practitioners (GPs), workload, medical activities, and personal and technical
      resources of practices. The investigated CAM disciplines were anthroposophic
      medicine, homoeopathy, traditional Chinese medicine, neural therapy and herbal
      medicine. MATERIAL AND METHODS: We designed a cross-sectional study with
      convenience and stratified samples of GPs providing conventional (COM) and/or
      complementary primary care in Switzerland. The samples were taken from the
      database of the Swiss medical association (FMH) and from CAM societies. Data were
      collected using a postal questionnaire. RESULTS: Of the 650 practitioners who
      were included in the study, 191 were COM, 167 noncertified CAM and 292 certified
      CAM physicians. The proportion of females was higher in the population of CAM
      physicians. Gender-adjusted age did not differ between CAM and COM physicians.
      Nearly twice as many CAM physicians work part-time. Differences were also seen
      for the majority of structural characteristics such as qualification of
      physicians, type of practice, type of staff, and presence of technical equipment.
      CONCLUSION: The study results show that structural characteristics of primary
      health care do differ between CAM and COM practitioners. We assumed that the
      activities of GPs are defined essentially by analyzed structures. The results are
      to be considered for evaluations in primary health care, particularly when
      quality of health care is assessed.

PMID- 16980772
TI  - [Attacks of apnea in a newborn aged 18 days].
AB  - Clinical case of an 18-day-old newborn of the 40th + 1 pregnancy week with
      postpartum respiratory adjustment disorder including periodical decreases in
      blood oxygen saturation. On day 8 postpartum the newborn developed myoclonic
      cramps of unknown origin combatted with phenobarbital. 6 days later Cheyne-Stokes
      breathing began under normal phenobarbital level being the cause for an
      additional homeopathic therapy trial. After a single dose of opium C 30 the
      breathing improved significantly, suspending the breaks in breathing and the
      decreases in blood oxygen saturation.

PMID- 16980775
TI  - Embarking on a journey: Implementing bar coding.

PMID- 16980776
TI  - The benefits of a preimplementation phase in electronic medical record
      implementation project.

PMID- 16980777
TI  - Using formulas for data analysis in excel: Creating a grade point average
      calculator.

PMID- 16980778
TI  - Development of theory-based, online health learning modules for older adults:
      Lessons learned.
AB  - Recently, the number of older adult online users has increased rapidly. In 2004,
      22% of Americans aged 65 years or older (about 8 million) used the Internet, and
      66% of them performed online searches for health information. The Web, therefore,
      can serve as a useful medium to educate older adults on selected health topics.
      In this study, the researchers developed four Web-based learning modules related
      to hip fracture prevention and tested the usability of these modules employing
      eight older adult online users. The findings from the usability tests
      demonstrated that the online learning modules were usable to the older adult
      participants. Additionally, these individuals could acquire health knowledge
      using these online modules. The important lessons learned through the research
      process will assist the researchers in conducting further studies in using health
      Web learning modules for older adults. A further study will be conducted to test
      the effects of these modules on preventing hip fractures.

PMID- 16980779
TI  - The design, marketing, and implementation of online continuing education about
      computers and nursing informatics.
AB  - Asynchronous online tutorials using PowerPoint slides with accompanying audio to
      teach practicing nurses about computers and nursing informatics were designed for
      this project, which awarded free continuing education units to completers.
      Participants had control over the advancement of slides, with the ability to
      repeat when desired. Graphics were kept to a minimum; thus, the program ran
      smoothly on computers using dial-up modems. The tutorials were marketed in live
      meetings and through e-mail messages on nursing listservs. Findings include that
      the enrollment process must be automated and instantaneous, the program must work
      from every type of computer and Internet connection, marketing should be live and
      electronic, and workshops should be offered to familiarize nurses with the online
      learning system.

PMID- 16980781
TI  - Nursing administrators' experiences in managing PDA use for inpatient units.
AB  - The adoption of information technology in patient care has become a trend in
      healthcare organizations. The impact of this technology on end users has been
      widely studied, but little attention has been given to its influence from a
      management perspective. The purpose of this study was to explore nurse managers'
      perceived experiences in implementing a policy to adopt personal digital
      assistant technology. A descriptive, exploratory qualitative approach (one-on
      one, in-depth interviews) was used to collect data from 16 nurse managers of
      inpatient units at a medical center in Taiwan. Interview data were analyzed
      according to Miles and Huberman's data reduction, data display, and conclusion
      verification process. The results revealed that nurse managers experienced the
      limitations of technology, training issues, doctors' obstructive influence, role
      conflict, and improvement of future personal digital assistant use. These results
      can be used to improve strategic organizational planning and in-service training
      programs to implement information systems.

PMID- 16980782
TI  - Standardized nursing language in the systematized nomenclature of medicine
      clinical terms: A cross-mapping validation method.
AB  - Many standardized healthcare languages have been mapped to the Systematized
      Nomenclature of Medicine Clinical Terms known as SNOMED CT, which was developed
      by the College of American Pathologists. This study describes a methodology for
      detecting misassigned concepts from source systems to SNOMED CT and presents the
      results of applying this methodology to a subset of concepts from two
      standardized nursing languages, the Nursing Interventions Classification and the
      Nursing Outcomes Classification. The methodology is based on comparing the
      knowledge representations of a set of nursing concepts between source systems
      (nursing languages) and SNOMED CT. If any nursing concept differs in knowledge
      representation in the target system compared with the source system, editorial
      misassignment of the concept was declared and recommendations for target system
      developers were made. In a total of 75 nursing concepts used to test this method,
      five misassigned concepts(6.6%) were found in SNOMED CT. This method can be used
      to validate other healthcare languages.

PMID- 16980785
TI  - Clinical doctorates: meeting the pubic need?

PMID- 16980786
TI  - The National Association of Clinical Nurse Specialists and the doctorate of
      nursing practice.

PMID- 16980789
TI  - Translating instruments into other languages: basic considerations.

PMID- 16980790
TI  - Viagra and vision loss: what is known and unknown.

PMID- 16980791
TI  - On intrapreneurship: from silos to collaboration.

PMID- 16980792
TI  - Brief reports for disseminating systematic reviews to nurses.
AB  - Much has been written about the importance of using research findings to guide
      nursing practice. How to best disseminate those findings to nurses remains a
      challenge. In many clinical settings, nurses interested in research utilization
      and evidence-based practice retrieve, review, and integrate knowledge from
      research reports to guide decisions about best practices. Major barriers to this
      approach, however, are staff nurses' lack of time, expertise, and resources for
      this process. One approach to overcoming these barriers is to disseminate the
      results of systematic research reviews directly to nurses in the form of brief
      reports, written in an easy-to-understand style, and sent via e-mail. This
      article describes the development of brief reports as a strategy for
      disseminating the results of systematic reviews to staff nurses. To demonstrate
      the use of brief reports for this purpose, we chose a systematic review published
      in the Cochrane Database of Systematic Reviews.

PMID- 16980794
TI  - Is there any food I can eat? Living with inflammatory bowel disease and/or
      irritable bowel syndrome.
AB  - INTRODUCTION: Inflammatory bowel disease (Crohn's disease and ulcerative colitis)
      and irritable bowel syndrome are chronic, debilitating gastrointestinal (GI)
      disorders. There are no known causes of inflammatory bowel disease and/or
      irritable bowel syndrome. Both of these GI conditions significantly impair
      quality of life and the ability to complete activities of daily living.
      Unfortunately, there has been little education and research surrounding the
      evaluation of effective coping strategies with respect to GI disorders,
      particularly from the perspective of those diagnosed. As such, exploring the
      strategies of individuals with GI disorders would provide information concerning
      coping strategies from the perspective of those afflicted. PURPOSE: The overall
      objective of this research was to explore the lived experience of women who had
      been diagnosed with inflammatory bowel disease and/or irritable bowel syndrome.
      This article specifically explores the relationship between food and irritable
      bowel syndrome and/or inflammatory bowel disease. METHODS: Eight females,
      diagnosed with inflammatory bowel disease and/or irritable bowel syndrome, were
      recruited via on-campus posters from a university in southern Ontario, Canada.
      Qualitative information was collected in the form of background questionnaires, e
      mail interviews, and face-to-face interviews, which were subsequently analyzed
      for trends. RESULTS: Every woman reported that one of the most significant means
      by which to cope with their condition centered around food consumption or
      controlling their food consumption. Subjects identified the importance of
      determining their "trigger foods," selecting healthy food choices, the impact of
      stress, and problems associated with food and travel. CONCLUSIONS: This research,
      predicated on the narratives of women diagnosed with GI disorders, substantiates
      the profound effect that food has on conditions of the GI tract. All of the women
      identified their relationship with food as a dynamic learning process, one that
      they thought would be a lifelong struggle. The implications for community health
      nurses in assisting individuals with GI disorders are discussed.

PMID- 16980795
TI  - Clinical nurse specialist practice within the Acute Care for Elders
      interdisciplinary team model.
AB  - As the complexity of care increases for hospitalized older adults, the clinical
      nurse specialist is essential for ongoing development of nursing practice and
      care standards. This article describes the Acute Care of the Elderly (ACE) model
      for interdisciplinary management of older adults and clinical specialist
      responsibilities within this interdisciplinary team. Within the model, clinical
      care specialists utilize clinical expertise and consultation skills reflecting
      three spheres of practice related to care of high-risk community-dwelling older
      adults admitted an acute medical unit. The goal for this patient group is to
      achieve medical stability while preserving maximum functioning. The Acute Care of
      the Elderly team members include primary nurses (staff nurses), physicians,
      clinical care specialists, therapies, social workers, dietitians, pharmacists,
      and a discharge planner. Under the leadership of the primarily nurse, the team
      develops a comprehensive care and discharge plan, implemented across a care
      continuum. Using protocols and working together, the team delivers cost
      effective, coordinated care that promotes process improvement resulting in
      practice that is in alignment with current standards of care.

PMID- 16980796
TI  - Profile. Janet M Bingle. Interview by Jo Ellen Rust.

PMID- 16980797
TI  - An interchange of humanity.

PMID- 16980800
TI  - Understanding patient experiences with goal setting for diabetes self-management
      after diabetes education.
AB  - Diabetes educators need to understand self-care experiences of patients with
      diabetes in the early stage after diagnosis and education. A survey assessed
      patient-generated measures of experiences with goals (self-care behaviors) after
      diabetes education among patients with type 2 diabetes (N = 97) between 6 months
      and 1.5 years since diagnosis. Most patients set goals during diabetes education
      and thought that the goals were useful. There is evidence suggesting that
      patients experiencing difficulty with traditional self-care behaviors may use
      approaches to evaluate their diabetes control that are not encouraged in diabetes
      education, such as monitoring their physical and emotional feelings. Implications
      for diabetes education and counseling practices are suggested.

PMID- 16980802
TI  - Assessing a community's elder friendliness: a case example of The AdvantAge
      Initiative.
AB  - The graying of our population has created a need for elder-friendly communities,
      but this concept has not been consistently defined nor applied in community
      assessments. Studies of the topic have examined a range of phenomena--physical
      environments, religious communities, and access to services--in an attempt to
      develop a comprehensive model for community assessment. This article describes an
      elder-friendly community model developed by The AdvantAge Initiative, discusses
      how it was used to identify assets and areas for improvement in one Western
      Washington community and how this assessment is informing strategies to improve
      older adults' quality of life.

PMID- 16980801
TI  - Providing asthma care in elementary schools: understanding barriers to determine
      best practices.
AB  - School nurses play a critical role in the management of children's asthma, yet
      they face barriers in their efforts to deliver quality care. In this qualitative
      study involving focus groups with school nurses, we identified key barriers in
      order to inform best practices. School nurses identified 4 main barriers to
      effective asthma care in elementary schools: lack of education, lack of
      communication, lack of resources, and lack of respect. An analysis of the
      barriers suggests that best practices for asthma care in elementary school
      settings require collaborative strategies that involve schools, families, the
      community, and the healthcare profession.

PMID- 16980803
TI  - Weight status and participation in senior center activities.
AB  - This study extends exploration of weight status and participation in senior
      center activities. Center staff surveyed 740 participants in 21 senior centers
      regarding personal characteristics, program participation, and weight status.
      Findings indicate participant characteristics exert a significant influence on
      weight status. Yet, weight status has no significant association with either
      program participation or perceived benefits from program participation.
      Strategies for influencing weight status through program interventions are
      reviewed and should interest those who view the senior center as a vehicle to
      enhance health and promote independent living for community-dwelling older
      adults.

PMID- 16980804
TI  - Childhood obesity: strategies for prevention.
AB  - The incidence of overweight children aged between 6 and 11 years has more than
      doubled while the incidence for adolescents from age 12 to 19 has tripled between
      1980 and 2000. The prevalence is highest among minorities and children belonging
      to low socioeconomic classes. Because overweight children tend to become obese
      adults, the future economic burden on the American healthcare system will be
      significant. This article examines the prevalence of the problem, highlights
      research and best practice models, and reviews policy trends related to childhood
      obesity.

PMID- 16980805
TI  - Adolescent sexual health & practice--a review of the literature: implications for
      healthcare providers, educators, and policy makers.
AB  - Regardless of the era, youth have engaged in activities that put them at risk and
      can compromise their health and well-being, in particular sexual experimentation.
      This article highlights current national and international literature focusing on
      adolescent sexual health related to health promotion and educational strategies.
      This information can be useful to family, educators, community health
      professionals, and policy makers in planning, implementing, and evaluating
      interventions that target adolescents of diverse cultural backgrounds.

PMID- 16980806
TI  - Impact of massage therapy on health outcomes among orphaned infants in Ecuador:
      results of a randomized clinical trial.
AB  - Diarrhea is the second leading cause of death among infants and young children in
      the developing world. This project investigated whether therapeutic infant
      massage could reduce diarrheal episodes and decrease overall illness of infants.
      Infants living in 2 orphanages in Quito, Ecuador, were matched by age and
      randomly assigned to an experimental or a control condition. The experimental
      group received an intervention, daily infant massage therapy by orphanage staff
      or volunteers, which lasted an average of 53 days, and symptoms of illness data
      were documented daily by volunteers in the orphanages. Results indicated that
      control group infants had a 50% greater risk of having diarrhea than experimental
      infants (rate ratio [RR] = 1.54, 95% confidence interval [CI] = 1.18, 2.03, P <
      0.001). Control group infants were also 11% more likely than experimental infants
      to experience illness of any kind (RR = 1.11, 95% CI = 0.96, 1.28, P = 0.17). The
      implications for the use of therapeutic infant massage, a remarkably inexpensive
      intervention, are discussed, and the need for further research is highlighted.

PMID- 16980807
TI  - Effects of regular exercise on pain, fatigue, and disability in patients with
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a major health problem in Korea. To explore the
      effects of regular exercise on pain, fatigue, and disability, a descriptive study
      was conducted in 435 Korean patients with RA. Exercisers were defined as those
      who are currently exercising more than 3 times a week, for at least 20 minutes,
      and for more than 6-consecutive months after being diagnosed with RA. The primary
      finding was that exercisers had significantly less fatigue and disability
      compared with nonexercisers. Results suggest that regular exercise has advantages
      for patients with RA to decrease fatigue and disability.

PMID- 16980808
TI  - Health literacy as an empowerment tool for low-income mothers.
AB  - Health literacy commonly refers to the extent to which one can access and
      accurately interpret healthcare information. Statistics reveal that limited
      health literacy is prevalent among those of lower socioeconomic status. When
      working with low-income mothers, it is recommended in this article that
      healthcare professionals operationalize a broader conceptualization of health
      literacy than assessment of reading levels and translating knowledge of risk
      factors for illness and disease. Nutbeam's continuum of functional, interactive,
      and critical health literacy directs healthcare professionals to expand their
      health education mandate to encompass equipping low-income mothers with the
      necessary knowledge and skills to gain control over their lives and optimize the
      healthy development of their children. Tenets from social cognitive theory,
      principles from interdependence theory, and strategies from Freire's empowerment
      education model are integral to successful progression along Nutbeam's health
      literacy continuum.

PMID- 16980809
TI  - Fabry disease: guidelines for the evaluation and management of multi-organ system
      involvement.
AB  - Fabry disease is an X-linked metabolic storage disorder due to the deficiency of
      lysosomal alpha-galactosidase A, and the subsequent accumulation of
      glycosphingolipids, primarily globotriaosylceramide, throughout the body. Males
      with classical Fabry disease develop early symptoms including pain and
      hypohidrosis by the second decade of life reflecting disease progression in the
      peripheral and autonomic nervous systems. An insidious cascade of disease
      processes ultimately results in severe renal, cardiac, and central nervous system
      complications in adulthood. The late complications are the main cause of late
      morbidity, as well as premature mortality. Disease presentation in female
      heterozygotes may be as severe as in males although women may also remain
      asymptomatic. The recent introduction of enzyme replacement therapy to address
      the underlying pathophysiology of Fabry disease has focused attention on the need
      for comprehensive, multidisciplinary evaluation and management of the multi-organ
      system involvement. In anticipation of evidence-based recommendations, an
      international panel of physicians with expertise in Fabry disease has proposed
      guidelines for the recognition, evaluation, and surveillance of disease
      associated morbidities, as well as therapeutic strategies, including enzyme
      replacement and other adjunctive therapies, to optimize patient outcomes.

PMID- 16980810
TI  - Diagnostic yield in the clinical genetic evaluation of autism spectrum disorders.
AB  - PURPOSE: Clinical geneticists are often asked to evaluate patients with autism
      spectrum disorders (ASDs) in reference to questions about cause and recurrence
      risk. Recent advances in diagnostic testing technology have greatly increased the
      options available to them. It is not currently clear what the overall diagnostic
      yield of a battery of tests, either collectively or individually, might be. The
      purpose of this study was to evaluate the diagnostic yield of a stepwise approach
      we have implemented in our clinics. METHODS: We used a three-tiered neurogenetic
      evaluation scheme designed to determine the cause of ASDs in patients referred
      for clinical genetic consultation. We reviewed the results of our diagnostic
      evaluations on all patients referred with a confirmed diagnosis of autism over a
      3-year period. RESULTS: By using this approach, we found an overall diagnostic
      yield for ASDs of more than 40%. This represents a significant increase in the
      diagnostic yield reported just a few years ago. CONCLUSIONS: Given the
      implications of these diagnoses on recurrence risk and associated medical
      conditions, a targeted neurogenetic evaluation of all persons with ASDs seems
      warranted. We discuss the issues in the future implementation of a fourth tier to
      the evaluation with the potential for an even higher diagnostic yield.

PMID- 16980811
TI  - Comprehensive genetic analysis of the cystic fibrosis transmembrane conductance
      regulator from dried blood specimens--implications for newborn screening.
AB  - PURPOSE: In the United States, approximately 1/3,700 babies is born with cystic
      fibrosis each year. The >1,300 documented sequence variants pose a challenge for
      detection of cystic fibrosis through genetic screening. To investigate whether
      comprehensive characterization of the cystic fibrosis gene is feasible using
      dried newborn blood specimens, we modified the whole blood Ambry Test: CF and
      determined its sensitivity by testing DNA from individuals with cystic fibrosis
      who still had unknown mutations after commercial mutation panel testing. METHODS:
      DNA from 42 archived newborn dried blood specimens of affected Hispanic, African
      American and Caucasian individuals in California was analyzed by temporal
      temperature gradient electrophoresis screening and targeted sequencing, and by
      gross deletion analysis. RESULTS: Excluding two specimens that could not be
      analyzed due to poor DNA quality, we report a 100% sensitivity and clinical
      detection rate in the remaining 40 patients. Eighty-three mutations representing
      40 different variants were detected, including 8 novel mutations. CONCLUSIONS:
      This study demonstrates the feasibility of temporal temperature gradient
      electrophoresis-based full sequence analysis and targeted sequencing from DNA in
      newborn blood specimens. The Ambry Test: CF, as an additional step in cystic
      fibrosis newborn screening models, can be used to dramatically reduce the number
      of cystic fibrosis carrier sweat test referrals.

PMID- 16980812
TI  - Exploring barriers to long-term follow-up in newborn screening programs.
AB  - PURPOSE: To inform current policy debate regarding the public health role in long
      term follow-up for individuals with disorders identified through state newborn
      testing efforts, by identifying and assessing key challenges, quality assurance
      activities, and long-term follow-up perceptions of state newborn screening
      programs. METHODS: A 23-question, web-based survey sent to newborn screening
      programs in all 50 states and Washington, DC, during January and February, 2005.
      RESULTS: Many U.S. newborn screening programs do not currently engage in
      structured long-term follow-up for newborns with diagnosed disorders. The newborn
      screening programs that do long-term follow-up face various challenges that may
      impact their ability to perform it effectively. Barriers include a lack of
      comprehensive quality assurance practices, outsourcing, financial constraints,
      and perceived communication problems with providers who treat these patients.
      CONCLUSIONS: A more in-depth analysis of the desired and feasible roles that
      should be played by newborn screening programs in long-term follow-up is needed.
      The wide variability within programs regarding the structure and implementation
      of long-term follow-up, and the relative absence of long-term follow-up systems
      components in some newborn screening programs, poses an interesting question
      regarding responsibility for evaluation of longer-term outcomes associated with
      newborn testing and disorder diagnosis.

PMID- 16980813
TI  - Population-based study of the prevalence of family history of cancer:
      implications for cancer screening and prevention.
AB  - PURPOSE: Family history assessment is gaining importance as a potential public
      health tool to help determine susceptibility to common cancers. Population-based
      data on the prevalence of having a family history of common cancers are scant.
      METHODS: We queried survey questions from the National Health Interview Survey,
      an annual nationwide survey of approximately 36,000 households in the United
      States, to determine the prevalence of persons reporting one or more first-degree
      relatives with breast, colorectal, lung, prostate, or ovarian cancer. RESULTS:
      Breast cancer was the most common condition noted for family members (7.74% of
      respondents), followed by lung cancer (7.10%), colorectal cancer (4.96%),
      prostate cancer (4.68%), and ovarian cancer (1.79%). A family history of cancer
      was more commonly reported by older persons, whites, women, and high-income
      groups. CONCLUSION: A substantial proportion of persons in the United States
      report having a close family member with cancer, and thus may be eligible for
      earlier or more aggressive cancer screening services.

PMID- 16980814
TI  - Low rates of acceptance of BRCA1 and BRCA2 test results among African American
      women at increased risk for hereditary breast-ovarian cancer.
AB  - PURPOSE: This study evaluated rates of BRCA1 and BRCA2 (BRCA1/2) test result
      acceptance among African American women and identified determinants of test
      result acceptance. METHODS: Acceptance of BRCA1/2 test results was evaluated
      among 157 African American women at high and moderate risk for having a BRCA1/2
      mutation who were offered genetic testing as part of a clinical genetic
      counseling research program. RESULTS: Twenty-two percent of women received
      BRCA1/2 test results. Test result acceptance differed between women with > or
      =10% prior probability of having a BRCA1/2 mutation (34%) and those who had a 5%
      prior probability (8%). Among women with > or =10% prior probability, test result
      acceptors were most likely to be married (OR = 5.29, 95% CI = 1.82, 15.38, P =
      0.002) and be less certain about their risk of developing cancer (OR = 3.18, 95%
      CI = 1.04, 9.80, P = 0.04). CONCLUSION: These results demonstrate that acceptance
      of BRCA1/2 test results may be limited among African American women. Being
      married and having less certainty about one's cancer risk may motivate acceptance
      of BRCA1/2 test results among African American women. It may be important to
      emphasize the possibility that BRCA1/2 test results may not clarify cancer risks
      during pre-test counseling with African American women to ensure informed
      decision-making about testing.

PMID- 16980815
TI  - Concordance of functional in vitro data and epidemiological associations in
      complex disease genetics.
AB  - PURPOSE: We aimed to assess whether epidemiological evidence on genetic
      associations for complex diseases concord with in vitro functional data. METHODS:
      We examined 36 studies on bi-allelic markers and 23 studies on haplotypes where
      investigators had addressed both epidemiological associations and the functional
      effect of the same gene variants in luciferase reporter systems in vitro.
      RESULTS: There was no correlation between epidemiological odds ratios and
      luciferase activity ratios (-0.09, P = 0.60). Luciferase activity ratios could
      not tell whether a probed epidemiologic association would be significant or not
      (area under receiver operating characteristics curve, 0.52). Luciferase results
      usually were qualitatively similar across cell lines and experimental conditions,
      with some exceptions. A luciferase activity ratio of 1.44 adequately separated
      statistically significant from non-significant functional differences (area under
      receiver operating characteristics curve, 0.95). Binary and continuous disease
      outcomes usually gave concordant results; other in vitro methods, in particular
      EMSA, agreed with luciferase results. Selective reporting and use of different
      variants and contrasts between functional and epidemiological analyses were
      common in these studies. CONCLUSIONS: In vitro biological data and epidemiology
      provide independent lines of evidence on complex diseases. We provide suggestions
      for improving the design and reporting of studies addressing both in vitro and
      epidemiological effects.

PMID- 16980816
TI  - Cholesterol and saturated fat intake determine the effect of polymorphisms at
      ABCG5/ABCG8 genes on lipid levels in children.
AB  - PURPOSE: Analysis of mutations in genes of the cholesterol metabolic pathway has
      not completely explained the interindividual variability of blood cholesterol
      concentrations attributed to gene-nutrient interactions. Thus, we analyzed
      polymorphisms in the ABCG5 and ABCG8 genes, involved in the regulation of
      intestinal cholesterol absorption, with special interest in a potential
      interaction with diet to determine lipid levels. METHODS: The polymorphisms ABCG5
      C1950G (Gln604Glu) and ABCG8 C1895T (Ala640Val) were determined by polymerase
      chain reaction and restriction analysis in 1227 healthy school children, aged 6
      to 8 years. RESULTS: No significant differences were found in blood lipid levels
      between subjects with different genotypes of the two analyzed polymorphisms.
      However, important differences appeared when separating subjects by their
      different lipid intake. The presence of the ABCG8 C1895T and ABCG5 C1950G
      polymorphisms was associated with different plasma total cholesterol, low-density
      lipoprotein cholesterol complex, and apolipoprotein B levels only in low
      cholesterol consumers (significantly for the C1895T polymorphism), and among
      children within the lower tertile of saturated fat intake (significantly for the
      C1950G polymorphism). CONCLUSION: Polymorphisms at the half-transporter ABCG5 and
      ABCG8 genes affect blood cholesterol concentrations in prepubertal children by
      influencing dietary responsiveness. This highly significant gene-nutrient
      interaction could explain the great individual differences in the plasma lipid
      response to cholesterol and fat intake.

PMID- 16980818
TI  - The management and mismanagement of time by deans.
AB  - Many new nursing leaders assuming deanships or assistant or interim deanships
      have limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department,
      both deans, offer survival tips based on their personal experiences and insights.
      They address common issues, challenges, and opportunities that academic executive
      teams face, such as negotiating an executive contract, obtaining faculty lines,
      building effective work teams, managing difficult employees, and creating nimble
      organizational structure to respond to changing consumer, healthcare delivery,
      and community needs. The authors welcome counterpoint discussions with readers.

PMID- 16980819
TI  - Technology and reflective practice: the use of online discussion to enhance
      postconference clinical learning.

PMID- 16980820
TI  - Create a low-cost tracheotomy model for suctioning simulation.
AB  - Use of simulation for nursing skill development can provide effective learning
      while minimizing risk to patients. However, simulators are expensive and
      portability can be limited. The author describes how to create a low-cost model
      for simulating tracheotomy suctioning and care. Construction is simple, with
      estimated materials cost for making the model less than 100 dollars.

PMID- 16980821
TI  - An innovative clinical practicum to teach evidence-based practice.
AB  - A clinical practicum was successfully implemented for RN to BSN students to apply
      evidence-based practice to actual clinical problems affecting nursing practice.
      The author describes how this practicum was implemented and the requisite
      resources and support systems. This senior-level capstone course enabled students
      to understand and value a lifelong learning approach to evidence-based practice.

PMID- 16980822
TI  - Optimizing evaluation of nursing education programs.
AB  - Program evaluation data must be meaningful, credible, objective, and responsive.
      The content, inputs, process, and product model provides an effective and useful
      framework for organizing the evaluation process. The model is a
      decision/accountability-oriented approach that emphasizes both proactive and
      retroactive evaluation to assess program improvement and quality. The authors
      describe the steps used in developing an evaluation plan to address
      undergraduate, graduate, and specialty standards and to serve as a framework for
      data collection, decision-making, continuous quality improvement, and
      demonstration of outcomes.

PMID- 16980823
TI  - Retaining older nurses in bedside practice.

PMID- 16980824
TI  - At-risk students: do theory grades + standardized examinations = success?
AB  - Early identification of students at risk of failing the National Council
      Licensure Examination for Registered Nurses allows nurse educators and students
      the opportunity to develop a remediation plan. The author describes one program's
      systematic review and exploration of the predictive ability of standardized
      examinations, nursing course theory grades, and entrance criteria for identifying
      students at risk. Best predictors at 3 points in the curriculum (entrance,
      midway, and the semester before graduation) are discussed.

PMID- 16980825
TI  - Curriculum design to promote the critical thinking of accelerated bachelor's
      degree nursing students.
AB  - This project describes the curriculum design of an accelerated bachelor's degree
      nursing program intended to promote the critical thinking of its students. Course
      objectives and teaching-learning strategies are described. Rogers' unitary view
      of human beings supports critical thinking as a developing process that should be
      measured in the context of nursing practice. Pre- and post-program critical
      thinking test scores indicated significant growth for the 38 graduates in the
      first 4 consecutive classes tested.

PMID- 16980826
TI  - Positioning advanced practice nurses for financial success in clinical practice.
AB  - Advanced practice nurses (APNs) are well prepared for patient care, but not for
      the financial aspects of clinical practice. A lack of reimbursement knowledge and
      skills limits the prospects for APNs to be key players in business and practice
      ventures. Faculty are challenged to strengthen the advanced practice
      reimbursement component of the financial management core to promote the
      reimbursement competency of APNs. The author discusses 4 primary content
      categories that are critical to financial success in clinical practice.

PMID- 16980827
TI  - A remediation process for nursing students at risk for clinical failure.
AB  - The authors propose a remediation process for nursing students at risk for
      clinical failure. The process is embedded within the context of clinical
      evaluation and includes the use of a learning contract as an integral component.
      The strengths and limits of the process and suggestions for further development
      are included.

PMID- 16980828
TI  - Short written assignments for clinical nursing courses.
AB  - The author describes how short written assignments can be used in clinical
      nursing courses to promote the development of critical thinking skills of
      students. With these assignments, students need to independently think about the
      clinical topic and are less likely to summarize what others have written. Many of
      these short papers can be done as activities in post clinical conferences and are
      critiqued by peers rather than faculty.

PMID- 16980829
TI  - Safety of healthcare: an amazing possibility.

PMID- 16980830
TI  - Building life skills for children with cystic fibrosis: effectiveness of an
      intervention.
AB  - BACKGROUND: With improved survival and the transformation in the course of cystic
      fibrosis (CF), there is a need to develop interventions to help children balance
      the physiologic and functional health demands of CF with psychosocial and
      developmental needs before the downward trajectory of CF intensifies in
      adolescence. OBJECTIVE: The aim of this study was to test the effectiveness of an
      intervention to improve psychosocial adjustment, functional health, and
      physiologic health in children (8-12 years of age) with CF by teaching them life
      skills for managing their chronic illness in their everyday lives. METHODS: A two
      group, experimental, repeated-measures design was used to compare 116 children
      with CF randomly assigned to intervention and usual care groups at baseline and
      at 3, 6, and 9 months post-intervention using repeated measures multivariate
      analysis of variance. Children received an individual, tailored intervention
      during a home visit and a structured group intervention. Four instruments were
      used to measure psychosocial health status: Perceived Illness Experience Scale,
      Self-Perception Profile for Children, Social Support Scale for Children, and
      Children's Loneliness Scale. Functional health status was measured with the
      Functional Disability Inventory for Children. Physiologic status was assessed as
      pulmonary function (FEV1%) and physical growth. RESULTS: Compared with children
      in the usual care group, the participants demonstrated decreased perceived impact
      of illness (p < .0001) and decreased loneliness (p < .0001). At 9 months, the
      improvements were maintained for impact of illness (p = .01) and loneliness (p =
      .01), remaining significantly different from baseline. CONCLUSION: This
      developmentally appropriate, problem-solving, and social skills intervention has
      promise for decreasing the social consequences of chronic illness (CF) in
      children's lives.

PMID- 16980831
TI  - A meta-analytic study of predictors for loneliness during adolescence.
AB  - BACKGROUND: Extensive research has been completed to investigate loneliness in
      adolescents over the past several decades; identification of key predictors for
      loneliness was needed using meta-analytic techniques. OBJECTIVES: To identify
      predictors for loneliness in adolescents through a comprehensive review of the
      literature and to use quantitative meta-analysis to determine the magnitude of
      the relationships between each predictor and loneliness. METHODS: The literature
      reviewed included 242 studies published or unpublished between 1980 and 2004, of
      which 95 met the inclusion criteria. Eleven key predictors for loneliness were
      identified in the 95 studies. A meta-analysis was conducted on each of the 11
      predictors in relation to loneliness. RESULTS: Four predictors (gender,
      depression, shyness, and self-esteem) had large effect sizes, four predictors
      (social support, social anxiety, maternal expressiveness, and paternal
      expressiveness) had large medium to medium effect sizes, two predictors (stress
      and self-disclosure) had low effect sizes, and one predictor (age) had a very low
      effect size. DISCUSSION: Theories of loneliness served as a framework for
      interpreting the findings of the meta-analysis. The most powerful predictors can
      be used in intervention studies aimed at reducing loneliness in adolescents.

PMID- 16980832
TI  - Testing the relationship between job stress and satisfaction in correctional
      nurses.
AB  - BACKGROUND: Correctional nurses function in a high stress environment due to the
      nature of their clients and the primacy of environmental security. Job stress and
      satisfaction are theorized relational concepts that influence intent to stay and
      turnover as described in the anticipated turnover model. An increased
      understanding of the nature and sources of stress and satisfaction provides
      necessary information about correctional nursing. OBJECTIVE: To (a) replicate an
      earlier study of correctional nurses to determine whether similar findings could
      be duplicated in a study of prison nurses from another state and (b) test the
      concepts of stress and satisfaction as represented in the anticipated turnover
      model. METHODS: Using the Index of Work Satisfaction and the Nurse Stress Index,
      a correlational mail survey was designed to assess job stress and satisfaction
      among 454 nurses in a northeastern state prison system. RESULTS: Overall stress
      scores were not significantly different from the original study despite
      differences in demographic characteristics. Highest to lowest mean scores on
      actual sources of satisfaction include physician-nurse interaction, autonomy,
      professional status, task requirements, organizational policies, and pay.
      Satisfaction scores were significantly higher in the original study. An inverse
      relationship exists between job stress and satisfaction among correctional
      nurses. Job stress was a significant predictor of job satisfaction, supporting
      the theorized conceptual relationship between job stress and job satisfaction as
      described in the anticipated turnover model. DISCUSSION: Stress levels and the
      top two sources of stress were essentially the same for both groups of
      correctional nurses. Sources of satisfaction are ranked similarly but subscale
      and overall scores indicate that the nurses in the replication study were more
      dissatisfied. Findings validate the theoretical proposition in the anticipated
      turnover model that job stress is a major predictor variable in explaining job
      satisfaction.

PMID- 16980833
TI  - Testing decisional balance and self-efficacy applied to workers' use of hearing
      protection.
AB  - BACKGROUND: The continued prevalence of low rates of hearing protection device
      (HPD) use by workers exposed to hazardous noise requires ongoing efforts to
      investigate ways to increase HPD use. OBJECTIVE: The aim of this study was to
      investigate the utility of the Transtheoretical Model (TTM) for research with
      factory workers' use of HPDs, specifically focusing on the model suppositions
      related to the constructs of decisional balance and self-efficacy. METHODS: Using
      secondary analysis, pretest measures were obtained through a randomized
      controlled clinical trial of an intervention to increase use of HPDs. The sample
      included in the analyses were factory workers (N = 1,245) exposed to hazardous
      noise in a Midwestern automotive manufacturing plant. Using analysis of variance
      (ANOVA), the TTM constructs pros, cons, and self-efficacy of HPD use were
      examined across stages. RESULTS: Using ANOVA, significant variance was found
      across stages of HPD use. Pros, cons, and self-efficacy significantly differed by
      stage of HPD use in predicted patterns: pros, F(4, 1240) = 46.29, p < .001; cons,
      F(4, 1240) = 17.14, p < .001; and self-efficacy F(4, 1240) = 7.32, p < .001. The
      crossover effect of pros and cons occurred in the preparation stage, as expected.
      CONCLUSIONS: Support was found for the presence of conceptually distinct stages
      of HPD use and the TTM predictions for decisional balance and self-efficacy
      across stages. Performance of the TTM constructs within current research on HPD
      use presents opportunities for increased tailoring of training for factory
      workers on use of HPDs.

PMID- 16980834
TI  - Effect of differentiation of self on adolescent risk behavior: test of the
      theoretical model.
AB  - BACKGROUND: Innovative theoretical models are needed to explain the occurrence of
      high-risk sexual behaviors, alcohol and other-drug (AOD) use, and academic
      engagement among ethnically diverse, inner-city adolescents. OBJECTIVE: The aim
      of this study was to test the credibility of a theoretical model based on the
      Bowen family systems theory to explain adolescent risk behavior. Specifically
      tested was the relationship between the predictor variables of differentiation of
      self, chronic anxiety, and social problem solving and the dependent variables of
      high-risk sexual behaviors, AOD use, and academic engagement. METHODS: An ex post
      facto cross-sectional design was used to test the usefulness of the theoretical
      model. Data were collected from 161 racially/ethnically diverse, inner-city high
      school students, 14 to 19 years of age. Participants completed self-report
      written questionnaires, including the Differentiation of Self Inventory, State
      Trait Anxiety Inventory, Social Problem Solving for Adolescents, Drug Involvement
      Scale for Adolescents, and the Sexual Behavior Questionnaire. RESULTS: Consistent
      with the model, higher levels of differentiation of self related to lower levels
      of chronic anxiety (p < .001) and higher levels of social problem solving (p <
      .01). Higher chronic anxiety was related to lower social problem solving (p <
      .001). A test of mediation showed that chronic anxiety mediates the relationship
      between differentiation of self and social problem solving (p < .001), indicating
      that differentiation influences social problem solving through chronic anxiety.
      Higher levels of social problem solving were related to less drug use (p < .05),
      less high-risk sexual behaviors (p < .01), and an increase in academic engagement
      (p < .01). CONCLUSIONS: Findings support the theoretical model's credibility and
      provide evidence that differentiation of self is an important cognitive factor
      that enables adolescents to manage chronic anxiety and motivates them to use
      effective problem solving, resulting in less involvement in health-comprising
      behaviors and increased academic engagement.

PMID- 16980835
TI  - Psychometric testing of the revised 15-item Bakas Caregiving Outcomes Scale.
AB  - BACKGROUND: Family caregivers of stroke survivors experience a variety of
      negative social, emotional, and health-related outcomes as a result of providing
      care. OBJECTIVES: : To psychometrically test the revised 15-item Bakas Caregiving
      Outcomes Scale (BCOS) measuring life changes specifically resulting from
      providing care. The original 10-item BCOS was improved by adding five items
      addressing financial well-being, level of energy, role functioning, physical
      functioning, and general health. METHODS: Psychometric testing of the revised 15
      item BCOS using a sample of 147 family caregivers of stroke survivors
      approximately 4 months after stroke was conducted to determine the quality of the
      items, internal consistency reliability, test-retest reliability, construct
      validity, and criterion-related validity. Most caregivers were women (78.9%),
      White (68.0%) or African American (29.9%), and either spouses (60.1%) or adult
      children (31.3%). RESULTS: Satisfactory evidence of internal consistency (alpha =
      .90) and 2-week test-retest reliability (intraclass coefficient [ICC] = .66; 95%
      confidence interval [CI] = 0.42-0.81) was provided, with item-to-total
      correlations ranging from .41 to .74. Unidimensionality was supported by
      confirmatory factor analysis with indices, indicating a good fit. Using
      hierarchical multiple regression, 36% of the BCOS variance was explained by
      constructs in the conceptual model [F(11,132) = 6.72, p < .001]. Criterion
      related validity was supported by correlations with the 36-item Short Form (SF
      36) General Health Subscale (r = .32, p < .001) and a criterion variable
      measuring how caregivers' lives had changed overall (r = .67, p < .001).
      DISCUSSION: The revised 15-item BCOS has evidence of satisfactory reliability and
      validity in family caregivers of stroke survivors. The BCOS is a valuable measure
      in research and can be used to identify priority areas for nursing interventions
      designed to improve caregivers' outcomes.

PMID- 16980836
TI  - Impact of uncertainty, social support, and prenatal coping on the psychological
      well-being of high-risk pregnant women.
AB  - BACKGROUND: The effects of uncertainty and social support on the psychological
      well-being of high-risk pregnant women may be influenced by their prenatal coping
      strategies. OBJECTIVE: The purpose of this study was to investigate whether
      prenatal coping strategies (preparation for motherhood, avoidance, positive
      interpretation of events, and prayer) mediate the effects of uncertainty and
      social support on the psychological well-being of high-risk pregnant women.
      METHODS: A cross-sectional, descriptive, correlational design was used. The
      convenience sample consisted of 105 high-risk pregnant women 18-34 years of age
      and at 24-36 weeks gestation. The main measures were Mishel Uncertainty in
      Illness Scale, Medical Outcomes Study Social Support Survey, Prenatal Coping
      Inventory, and Psychological General Well-Being Index. Data analysis included
      descriptive statistics, correlational techniques, and path analyses. RESULTS: The
      women reported low levels of uncertainty, moderate levels of distress, and high
      levels of social support. Prayer was the most frequently used prenatal coping
      strategy, whereas avoidance was used least often. Women who reported higher
      levels of uncertainty also reported less social support (r = -.45, p < .01), less
      psychological well-being (r = -.48, p < .01), less positive interpretation (r = 
      .30, p < .01), and more use of avoidance (r = .43, p < .01). The modified path
      analysis showed good fit with the data. Avoidance significantly mediated the
      effects of uncertainty on psychological well-being (z = -2.74, p < .01). Social
      support had a significant direct effect on preparation for motherhood (beta =
      .43, z = 3.94, p < .001). DISCUSSION: Avoidance mediated the effect of
      uncertainty on psychological well-being for the high-risk pregnant women in this
      sample. The results of the study may help perinatal nurses to better understand
      how high-risk pregnancy affects these women.

PMID- 16980837
TI  - Cancer-related fatigue, depressive symptoms, and functional status: a mediation
      model.
AB  - BACKGROUND: Patients with cancer grapple with a confusing array of disease- and
      treatment-related symptoms while trying to maintain functioning in usual roles
      and daily activities. Research is needed to sort out and identify symptom
      clusters as a basis for a rational approach to symptom management. OBJECTIVE: The
      aim of this study was to test, through secondary analysis, a mediation hypothesis
      about the direct and indirect relationships between fatigue and depressive
      symptoms through a pathway involving functional status. METHODS: Data from the
      experimental and control groups of a randomized clinical intervention trial for
      fatigue management, collected after the second chemotherapy treatment or during
      the last week of radiotherapy, were analyzed. The mediation pathway from fatigue
      to depressive symptoms through functional status was tested separately for groups
      receiving either an energy conservation intervention or a control intervention,
      equating for time and attention. RESULTS: For the control group, the results
      indicate support for partial mediation. The previously significant relationship
      between fatigue and depressive symptoms was reduced after functional status was
      controlled, accounting for 43% of the total mediated effect. The mediation
      hypothesis was not supported in the energy conservation group, indicating that
      the intervention may have changed the role of functional status in mediating the
      effect of fatigue on depressive symptoms. DISCUSSION: In the control group, when
      routine activities became more difficult because of fatigue, individuals had more
      depressive symptoms. The results suggest that functional status is an important
      factor to consider in symptom management for fatigue. An appropriate intervention
      for fatigue would have two targets: the fatigue and strategies to reduce the
      likelihood of impaired functioning that could result in elevated depressive
      symptoms.

PMID- 16980838
TI  - Breast cerebrospinal fluid pseudocyst.

PMID- 16980839
TI  - Free anterolateral thigh perforator flap in a patient with systemic sclerosis and
      Raynaud's phenomenon.

PMID- 16980840
TI  - Free innervated sole of foot transfer for contralateral lower limb salvage.

PMID- 16980841
TI  - Injectable soft-tissue fillers: clinical overview.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Know the composition and biology of injectable fillers. 2. Understand the
      advantages and disadvantages of each injectable filler. 3. Understand the U.S.
      Food and Drug Administration regulatory status of each type of injectable filler,
      including their indications. BACKGROUND: The use of injectable filling agents for
      soft-tissue facial defects has a long history of successful use based on
      xenogeneic collagen materials. New materials of differing compositions for
      injection treatments either are now available or will soon be available for
      clinical use. METHODS: A review of the medical literature was performed to
      provide chemical compositions, methods of preparation, biological behavior, and
      clinical outcomes for every known injectable filler material that is either
      currently used or being evaluated in clinical trials. RESULTS: Hyaluronic acid
      based materials have now replaced animal or human-derived collagen as the
      standard injection materials. Synthetic alternatives offer the potential of
      longer lasting results, but the long-term outcome with their use in large numbers
      of patients is not yet known. CONCLUSIONS: As there is no single injectable
      filler that has all of the desired characteristics, understanding the advantages
      and disadvantages of one filler over another is extremely helpful in guiding the
      patient to an informed decision. Although all of the reviewed injectable fillers
      are safe, the concepts of their long-term volume persistence and how they compare
      with each other remain largely anecdotal, with few prospective controlled
      clinical trials.

PMID- 16980842
TI  - A single surgeon's 12-year experience with tissue expander/implant breast
      reconstruction: part I. A prospective analysis of early complications.
AB  - BACKGROUND: Multiple prior reports are conflicted regarding the true incidence of
      complications following implant-based breast reconstruction. A review of a single
      surgeon's extensive experience with tissue expander/implant reconstruction
      provides the opportunity to critically evaluate outcomes in a uniformly treated
      patient population. The objective of this study was to analyze the development of
      early complications in patients following two-stage implant breast
      reconstruction. METHODS: A review of all tissue expander/implant reconstructions
      performed by a single surgeon over the 12-year period from July of 1992 to June
      of 2004 was performed. A prospectively maintained database was analyzed with
      respect to reconstructive and early complication data on 1522 reconstructions in
      1221 patients. Early complications were defined as those occurring 12 months or
      less from initiation of reconstruction. RESULTS: The overall rate of early
      complications was 5.8 percent; the rate of premature expander removal was 2.7
      percent. The most common complication was infection (2.5 percent). The incidence
      of complications after tissue expander insertion (8.5 percent) was significantly
      higher than that after the exchange procedure (2.7 percent). The rate of
      complications was significantly higher in patients with a history of preoperative
      chest wall irradiation. There was no difference in the incidence of complications
      in patients who were expanded during chemotherapy and those who were not.
      CONCLUSIONS: Tissue expander/implant reconstruction is a safe, reliable method of
      reconstruction with minimal early complications. Early complications are more
      common after expander insertion. Chemotherapy administered during tissue
      expansion does not increase the rate of complications. The rate of complications,
      although higher in previously irradiated patients, remains low.

PMID- 16980843
TI  - A single surgeon's 12-year experience with tissue expander/implant breast
      reconstruction: part II. An analysis of long-term complications, aesthetic
      outcomes, and patient satisfaction.
AB  - BACKGROUND: Few reports have critically evaluated long-term outcomes following
      two-stage implant reconstruction. The objective of this study was to evaluate
      long-term aesthetic results, late complications, and patient satisfaction
      following tissue expander/implant breast reconstruction. A single surgeon's
      extensive experience with implant-based reconstruction provides an opportunity to
      evaluate these results in a uniformly treated patient population. METHODS: A
      total of 1522 tissue expander/implant reconstructions were initiated in 1221
      patients from July of 1992 to June of 2004. Data on a cohort of 315 patients (410
      reconstructions) with a minimum of 1 year of follow-up were entered into a
      prospectively maintained outcomes database. Overall aesthetic grade, capsular
      contracture grade, patient satisfaction, and late complications were
      prospectively evaluated, and outcome data were recorded on an ongoing basis.
      RESULTS: Mean follow-up was 36.7 months. Eighty-eight percent of patients had a
      good to excellent aesthetic result. Laterality of reconstruction (bilateral
      versus unilateral) and radiation history were significant predictors of overall
      cosmesis. Aesthetic results were not related to preoperative breast size, implant
      volume, or body mass index. Pathologic capsular contractures (grade III/IV)
      developed in 10.4 percent of patients. Four percent of all permanent implants
      were exchanged for a second prosthesis. Ninety-five percent of patients were
      satisfied with their reconstruction. CONCLUSIONS: Tissue expander/implant
      reconstruction yields good to excellent long-term aesthetic results in the
      majority of patients, and overall patient satisfaction remains high. Bilateral
      reconstructions have higher overall aesthetic grades. Reconstruction may be
      performed in patients with larger-volume breasts with satisfactory cosmesis.
      Successful outcomes are possible in patients who receive chest wall irradiation.

PMID- 16980844
TI  - Management of gestational gigantomastia.
AB  - BACKGROUND: Gigantomastia of pregnancy is a rare, severely debilitating condition
      characterized by massive enlargement of breasts and resulting in tissue necrosis,
      ulceration, infection, and, occasionally, hemorrhage. Typically, resolution of
      breast hypertrophy to near prepregnancy size occurs in the postpartum period.
      Treatment is controversial. METHODS: The authors present a patient with
      gestational gigantomastia for whom nonoperative management failed and who
      subsequently required bilateral mastectomies. In addition, the authors performed
      a comprehensive review of reported cases and generated a treatment algorithm.
      RESULTS: The patient tolerated the mastectomies well and went on to deliver a
      healthy child. Postpartum delayed breast reconstruction with tissue expansion and
      implant placement yielded good results. The literature review demonstrates that
      medical management has successfully avoided surgery during gestation in 39
      percent of cases since 1968. However, 35 percent of patients eventually underwent
      breast reduction (12 percent) or mastectomy (88 percent) during pregnancy.
      Spontaneous or elective termination of the pregnancy accounted for 30 percent of
      outcomes. Patients who underwent breast reduction and then became pregnant had a
      100 percent (four of four patients) chance of recurrence. Two women had
      mastectomy and subsequent pregnancies. One woman developed multiple small areas
      of recurrence that were surgically excised. The other woman had two additional
      pregnancies with no recurrence of symptoms. CONCLUSIONS: Medical therapies to
      manage gestational gigantomastia are inconsistent in outcome. Since some patients
      respond, these therapies are worth trying. However, if the patient and/or fetus
      are experiencing significant morbidity, then surgical intervention is warranted.
      Breast reduction or mastectomy with delayed reconstruction is the preferred
      procedure. If the mother is considering future pregnancies, mastectomy offers the
      lowest risk of recurrence.

PMID- 16980845
TI  - Differential gene expression between juvenile and adult dura mater: a window into
      what genes play a role in the regeneration of membranous bone.
AB  - BACKGROUND: Although reossification of large calvarial defects is possible in
      children, adults lack this tissue engineering capacity. In this study, the
      authors compared the differences in gene expression between juvenile and adult
      dura mater using a mouse cDNA microarray with 42,000 unique elements. METHODS:
      Non-suture-associated parietal bone was harvested from 6-day-old and 60-day-old
      mice. The dura mater was carefully dissected from the calvarial disk and snap
      frozen. RNA was extracted from pooled dura mater for microarray analysis. The 25
      most differentially expressed genes were listed, as were selected bone-related
      genes. In addition, quantitative real-time reverse-transcriptase polymerase chain
      reaction confirmation of selected genes-BMP-2, BMP-4, and BMP-7; and osteopontin
      (OP), osteocalcin (OC), and FGFR-1-was performed. RESULTS: Juvenile dura mater
      expressed significantly greater amounts of BMP-2 and OP. Minimal difference in OC
      expression was observed between juvenile and adult dura mater. Extracellular
      matrix proteins (Col3a1, 5a1, 6a1, and fibronectin 1), osteoblast differentiation
      markers (Runx2/Cbfa1, Itm2a, and FGFR-1), and the growth factor Ptn were among
      other genes with greater expression in juvenile dura mater. Markers of
      osteoclasts (Acp5, MMP9, Ctsk) and the multiple candidate gene Ntrk2 were also
      expressed at higher levels in the juvenile dura mater. CONCLUSIONS: These
      findings suggest a more differentiated osteoprogenitor population to exist along
      with a greater presence of osteoclasts in the juvenile dura mater relative to
      adults. In addition to establishing a baseline difference in gene expression
      between juvenile and adult dura mater, new genes potentially critical to the
      regenerative potential of juvenile calvaria were identified.

PMID- 16980846
TI  - Commercially available demineralized bone matrix compositions to regenerate
      calvarial critical-sized bone defects.
AB  - BACKGROUND: Demineralized bone matrix products are often used by surgeons to
      regenerate bone. Several different types of carriers have been combined with
      demineralized bone matrix to improve clinical handling and surgical outcome. The
      aim of the study was to quantitate bone regeneration in standard-sized calvarial
      defects (a critical-sized defect) in response to commercially available
      demineralized bone matrix formulations. METHODS: The commercial demineralized
      bone matrix formulations were tested as received in 8-mm-diameter calvarial
      critical-sized defects in an athymic rat model. The demineralized bone matrix
      treatment groups included the following: (1) Allomatrix; (2) demineralized bone
      matrix plus sodium hyaluronate (DBX); (3) DBX with poly(DL-lactide) mesh; 4)
      Dynagraft; (5) Grafton; (6) Regenafil; and (7) human demineralized bone matrix
      without a carrier. An eighth treatment was a poly(DL-lactide) mesh. At designated
      times of 2, 4, and 8 weeks, the critical-sized defects were recovered and
      processed for undecalcified histology and histomorphometry. Histomorphometric
      data were subjected to an analysis of variance and Fisher's protected least
      significant difference multiple comparison test. Significance was established at
      p <or= 0.05. RESULTS: Allomatrix, Dynagraft, Regenafil, and poly(DL-lactide) mesh
      alone had less bone formation than DBX, Grafton, DBX plus mesh, and demineralized
      bone matrix. CONCLUSIONS: DBX, DBX plus mesh, demineralized bone matrix, and
      Grafton produced more bone formation than Allomatrix, Dynagraft, mesh alone, and
      Regenafil.

PMID- 16980847
TI  - The composition and behavior of capsules around smooth and textured breast
      implants in pigs.
AB  - BACKGROUND: The surface of the implant is one of the many factors often
      associated with the occurrence of capsular contracture, the etiopathogeny of
      which remains unclear. The purpose of this study was to analyze the behavior of
      capsular contracture by means of applanation tonometry and histology using a
      midsized animal model. METHODS: Silicone breast implants were implanted into 33
      pigs and observed at 30, 60, 180, and 270 postoperative days. RESULTS: Capsular
      contracture in smooth implants showed significantly greater pressure values of
      tonometry, and the smooth implant capsule was significantly thicker than the
      textured implant capsule. Both pressure and thickness of the capsules increased
      at each period. The collagenous layer did not show any difference considering the
      periods of time in which the total thickness was analyzed; on the other hand, the
      increase in total capsular thickness occurred by thickening of the noncollagenous
      layer in both smooth and textured implants. Taking into consideration both kinds
      of implants, histomorphometric analysis showed that thin fibers were replaced by
      thick fibers in later postoperatives periods (180 and 270 days). CONCLUSIONS: The
      greater incidence of capsular contracture in smooth implants was correlated with
      the progressive increase in total capsule thickness, due to a higher
      concentration of collagenous fibers, when compared with textured implants (p =
      0.011; mean difference, 6.61), and a higher concentration of thick fibers (p =
      0.034; average, >5.51 percentage points per field of thick fibers than the
      textured implants in all periods). Pigs are good animal models for studying the
      healing process after breast augmentation with implants.

PMID- 16980849
TI  - A new Z-epicanthoplasty and a concomitant double eyelidplasty in Chinese eyelids.
AB  - BACKGROUND: Patients with no double eyelid folds and with a mild or moderate
      medial epicanthus are most typically Asians. After only receiving double
      eyelidplasty, they often complain that their eyes look round and their eyelid
      fissures are shorter because their medial epicanthi still exist. METHODS: In this
      article, according to the authors' surgical findings, it is reasoned that the
      malpositioned portion of the orbicularis oculi muscle fibers is the main cause of
      congenital medial epicanthus. Several design principles for performing the Z
      epicanthoplasty concomitant with a double eyelidplasty were advanced: (1) removal
      of the main deformity-formed cause, (2) correcting the pretarsal skin shortage in
      the medial upper eyelid, (3) preventing the prominent scarring in the medial
      canthal area, and (4) achieving other advantages (i.e., easy design and
      operation, precision of performance with a concomitant double eyelidplasty, and
      excellent and reproducible results). RESULTS: Epicanthoplasty only was performed
      in six patients. An epicanthoplasty concomitant with a double eyelidplasty was
      performed in 230 cases with congenital or traumatic medial epicanthi. Sixty-seven
      cases in this series were followed up for 4 to 23 months (average, 7 months). The
      contours of the double eyelids were natural. Mild scar proliferation was observed
      in all of the patients in the early postoperative period and then would diminish
      and become a gray-white line. Some skin wrinkles and skin shadow on the B flap
      could be seen. CONCLUSIONS: The indications for this procedure are all types of
      medial epicanthi but the inversus type. Older age is a relative contraindication.

PMID- 16980848
TI  - Smile reconstruction in adults with free muscle transfer innervated by the
      masseter motor nerve: effectiveness and cerebral adaptation.
AB  - BACKGROUND: This study assesses the ability of the masseter motor nerve
      innervated microneurovascular muscle transfer to produce an effective smile in
      adult patients with bilateral and unilateral facial paralysis. METHODS: The
      operation consists of a one-stage microneurovascular transfer of a portion of the
      gracilis muscle that is innervated with the masseter motor nerve. The muscle is
      inserted into the cheek and attached to the mouth to produce a smile. The
      outcomes assessed were the amount of movement of the transferred muscle; the
      aesthetic quality of the smile; the control, use, and spontaneity of the smile;
      and the functional effects on eating, drinking, and speech. The study included 27
      patients aged 16 to 61 years who received 45 muscle transfers. RESULTS: All 45
      muscle transfers developed movement. The commissure movement averaged 13.0 +/-
      4.7 mm at an angle of 47 +/- 15 degrees above the horizontal, and the mid upper
      lip movement averaged 8.3 +/- 3.0 mm at 42 +/- 17 degrees. Age did not affect the
      amount of movement. Patients older than 50 years had the same amount of movement
      as patients younger than 26 years (p = 0.605). Ninety-six percent of patients
      were satisfied with their smile. CONCLUSIONS: A spontaneous smile, the ability to
      smile without thinking about it, occurred routinely in 59 percent and
      occasionally in 29 percent of patients. Eighty-five percent of patients learned
      to smile without biting. Age did not affect the degree of spontaneity of smiling
      or the patient's ability to smile without biting.

PMID- 16980850
TI  - Visual analogue scale scoring and ranking: a suitable and sensitive method for
      assessing scar quality?
AB  - BACKGROUND: The field of scar assessment lacks a standard methodology. Previous
      methods have focused on a wide range of scar types, resulting in poorer
      sensitivity and diminishing their discriminatory effectiveness. METHODS: As part
      of a clinical trial investigating the scar-improving efficacy of transforming
      growth factor-beta3, the authors investigated the use of a visual analogue scale
      and scar ranking as scar assessment tools. Scar photographic images were assessed
      using a newly developed computerized scar assessment system by an external lay
      panel. RESULTS: A total of 4296 scar images were collected for visual analogue
      scale assessment and 2148 scar pairs were collected for scar ranking. Intrarater
      consistency was 100 percent for the ranking data, with differences very close to
      zero for the visual analogue scale consistency data. Reducing the number of
      assessors in the external panel significantly improved intraclass correlation
      coefficients. From month 1 to month 12, the correlation coefficients for the
      difference in visual analogue scale score showed that the assessors reliably
      noted the changes in the maturing scars. Combining logistic regression with an
      area under the curve of 0.72 in a receiver operating characteristic curve
      analysis, the visual analogue scale score was shown to be a highly statistically
      significant predictor of a good scar. CONCLUSIONS: The authors have shown the
      visual analogue scale scar scoring and scar ranking methods to be consistent,
      reliable, valid, and feasible. These methods for scar assessment are highly
      sensitive and capable of reliably measuring differences in scar quality, making
      them valuable techniques, reaching an unmet clinical need, and enabling
      investigation of changes in scar quality (e.g., with time or after therapeutic
      intervention).

PMID- 16980851
TI  - Omental transposition flap for salvage of ventricular assist devices.
AB  - BACKGROUND: The use of ventricular assist devices for patients with end-stage
      cardiac failure awaiting heart transplantation has become increasingly common.
      Ventricular assist devices improve the longevity and the quality of life for
      these patients. In addition, they serve as a bridge to cardiac allograft
      transplantation until a donor heart is found. However, ventricular assist device
      related infections remain a major problem complicating their long-term use.
      Clinical infection and sepsis can critically threaten these patients with
      ventricular assist devices. Infection can delay immediate transplantation and
      potentially require the removal of the device for definitive treatment of the
      problem. METHODS: Patients who underwent insertion of a ventricular assist device
      at the University of Pittsburgh Medical Center were identified through accessing
      the medical records archives of the hospital. Review of patients' medical records
      was conducted to obtain patient demographics, preoperative diagnosis and disease
      state, type of ventricular assist device inserted, postoperative day of
      ventricular assist device infection onset, infectious organism identified, timing
      of omental flap procedure after the initial insertion, duration of ventricular
      assist device support before cardiac transplantation, and patient follow-up.
      RESULTS: There were 76 patients who underwent a ventricular assist device
      insertion procedure during the 4-year period between January of 2000 and January
      of 2004. Of the 76 patients who received a device, 11 (14 percent) had evidence
      of clinical infection secondary to insertion. Two of these 11 patients died
      before surgical intervention, four had their devices explanted, and the remaining
      five underwent omental flap transposition with bilateral pectoralis major
      advancement flaps in surgically addressing their infections. Of the five patients
      with infections who received omental transposition flaps, two went on to undergo
      successful transplantation, two continue to await cardiac allograft
      transplantation, and one died as a result of an unknown cause. CONCLUSIONS: The
      authors present their experience with five patients who received omental
      transposition flaps to cover infected ventricular assist device pumps and the
      associated tubing in large, open sternoabdominal wounds. Treatment included the
      direct application of an omental transposition flap over the infected device with
      use of a bilateral pectoralis advancement flap to aid in complete sternal and
      skin closure of the sternal wound defect. In each of these cases, the use of the
      omental flap was followed by resolution of the mediastinal infection. In
      addition, the treatment with an omental flap prevented the removal of infected
      devices in patients who were otherwise pump dependent during their waiting
      periods for transplantation. The use of omental transposition flaps can be an
      effective technique in salvaging infected ventricular assist devices and
      preserving this valuable device for patients awaiting a cardiac transplant.

PMID- 16980853
TI  - Efficacy of the handheld Doppler in preoperative identification of the cutaneous
      perforators in the anterolateral thigh flap.
AB  - BACKGROUND: Preoperative localization of the cutaneous perforators is an
      important step in designing anterolateral thigh flaps. The purpose of this study
      was to examine the accuracy of two commonly used Doppler devices in locating
      these perforators. METHODS: This study was conducted in 100 free anterolateral
      thigh flaps during a 2-year period. Cutaneous perforators of the anterolateral
      thigh flaps were localized in the clinic using the Huntleigh Mini Dopplex D-900
      unit with an 8-MHz probe (Huntleigh Diagnostics Ltd., Cardiff, United Kingdom)
      and in the operating room just before surgery using the Koven ES-100X Mini
      Doppler unit with a 10-MHz sterile probe (Koven Technology, Inc., St. Louis,
      Mo.). The locations of Doppler signals and of the actual cutaneous perforators at
      surgery were plotted and compared. RESULTS: One to three cutaneous perforators of
      the anterolateral thigh flap were consistently found at specific locations; they
      were named perforators A, B, and C from proximal to distal. Perforators A, B, and
      C were present in 51, 89, and 62 cases, respectively, at surgery and were
      approximately 5 cm apart. The sensitivities and specificities in detecting
      perforator B were 100 percent and 0 percent, respectively, for the Huntleigh
      Doppler unit, and 91 percent and 55 percent for the Koven unit. The Doppler
      signal was within 1 cm of the actual perforator B location in 74 percent and 70
      percent of the flaps with the Huntleigh and Koven units, respectively. The
      accuracy of Doppler examination decreased as body mass index increased.
      CONCLUSIONS: Preoperative handheld Doppler examination is not always accurate and
      should be used with caution in flap design.

PMID- 16980855
TI  - Microvascular free tissue transfer in patients with hematological disorders.
AB  - BACKGROUND: Microsurgical procedures performed in patients with hematological
      disorders can pose significant challenges. The literature is lacking in reports
      that specifically address the safety, reliability, and management techniques
      related to performing microvascular surgery in this group of patients. METHODS: A
      retrospective chart review of all patients with hematological disorders who
      received free flaps from 1995 to 2004 was performed. All patients had a
      hematologic work-up that confirmed the stability of the underlying disease. There
      were three male and three female patients with an average age of 27.6 years
      (range,12 to 63 years). Patients had leukemia (n = 2), hereditary spherocytosis,
      non-Hodgkin's lymphoma, and hemophilia (n = 2). Their defects were in the areas
      of the nasocolumella/upper lip, palate, palate and midface, and lower
      extremities. RESULTS: All patients received free flaps and all but one had an
      uneventful postoperative course. That patient, with hemophilia, 1 day after
      factor replacement was halted, had bleeding that required surgical re-exploration
      along with aggressive hematologic management. All flaps survived without vascular
      compromise. No wound infections were observed. All donor sites healed without
      complications. CONCLUSIONS: Essential ingredients in the treatment plan of
      patients with hematologic disorders undergoing free flaps include familiarity
      with the preoperative medical condition and potential postoperative
      complications, close monitoring of the patients and their medical condition
      before and after surgery, meticulous surgical technique, and close cooperation
      with the hematologists and infectious disease specialists. By following this
      regimen, patients with hematologic disorders and an otherwise stable medical
      history can undergo free tissue transfer safely and effectively with reliable
      outcomes.

PMID- 16980856
TI  - Surgery versus conservative therapy in carpal tunnel syndrome in people aged 70
      years and older.
AB  - BACKGROUND: Carpal tunnel syndrome is common in the general population, with a
      prevalence that increases with age. Although good satisfaction has been described
      after carpal tunnel release, little is known about the long-term outcome of
      treatment in elderly individuals with carpal tunnel syndrome. METHODS: The
      authors reviewed data from a population-based sample of 102 patients aged 70
      years and older with carpal tunnel syndrome. They used valid and sensitive mailed
      follow-up outcome [Boston Carpal Tunnel, satisfaction (American Academy of
      Orthopaedic Surgeons), and health status (Short Form-36) questionnaires to assess
      symptoms, functional status, expectations of treatment, and satisfaction with the
      results at a minimum of 2 years after initial diagnosis. RESULTS: Seventy
      patients with a mean age of 77.0 years (range, 70.2 to 88.5 years) responded to
      the survey, with a mean follow-up of 4.8 years. Patients who had surgery were
      more likely to have had more severe disease than those treated nonoperatively
      (Mantel-Haentzel test, p < 0.001). Satisfaction was 93 percent after surgical
      treatment and 54 percent after nonsurgical treatment. Patients who had surgery
      had significantly better relief of symptoms (t test, p < 0.01), functional status
      (t test, p < 0.05), satisfaction (t test, p < 0.001), and expectations with
      treatment (t test, p < 0.05) scores as compared with those who had nonsurgical
      treatment. CONCLUSIONS: In patients over the age of 70, surgery appears to be
      associated with better symptom relief, functional status, satisfaction, and
      expectations with treatment than nonoperative therapy does. Age should not be
      considered a contraindication for carpal tunnel surgery, nor should nonoperative
      therapy be favored in this age group.

PMID- 16980858
TI  - Venous supercharging of heterodigital artery flap.
AB  - BACKGROUND: The heterodigital artery island flap is a popular method of
      reconstruction for finger defects. Postoperative venous congestion is a common
      problem. METHODS: The authors present a technique to augment venous drainage of
      the flap. Briefly, the flap is harvested along with a dorsal vein that is then
      anastomosed to a recipient vein in an end-to-end fashion, after flap transfer and
      insetting. Using this technique, seven patients were operated on, ranging in age
      from 5 to 35 years (average age, 23 years). RESULTS: All flaps survived with no
      postoperative flap congestion, fully satisfying the reconstructive requirements.
      By this modification, skeletonization of the digital artery of the flap pedicle
      is safe if that approach is preferred, since there is no need to harvest
      periarterial fat for venous drainage. CONCLUSIONS: Providing good harmony with
      conventional methods and microsurgery, inclusion of a vein with the heterodigital
      artery island flap allows a more reliable and safer reconstructive choice for
      finger defects. Such a modification converts the unconventional venous
      circulation of the heterodigital artery island flap to a more physiologic one.

PMID- 16980859
TI  - Measuring surgeons' treatment preferences and satisfaction with nerve
      reconstruction techniques for children with unique brachial plexus birth palsies.
AB  - BACKGROUND: This study surveyed microsurgeons on treatments chosen for infants
      with brachial plexus birth palsies who have had failure of antigravity biceps
      and/or triceps function due to nerve surgery or natural history. METHODS:
      Questionnaires were sent to surgeons participating in a prospective multicenter
      brachial plexus birth palsy study. With a response rate of 82 percent, the sample
      comprised 22 surgeons with extensive experience in treating brachial plexus birth
      palsy. The survey gathered collective information on two unique clinical groups:
      (1) infants with no antigravity biceps function but intact antigravity deltoid
      and radial nerve function and (2) infants with no antigravity radial nerve
      function (wrist and digital extension, triceps) but intact antigravity biceps and
      deltoid function. Analysis of data and age-based trends was performed using the
      Fisher's exact test. RESULTS: With failure of biceps recovery, surgeons preferred
      microsurgery for children 6 to 18 months old and tendon transfers for children
      older than 18 months. Both procedures were preferred over observation alone (p <
      0.001). With regard to microsurgery techniques, with increasing age, surgeons
      used nerve transfers more than resected neuroma and grafting. With tendon
      transfers, regional transfers were performed more than 90 percent of the time at
      all ages. For patients with no antigravity radial nerve function, most cases at
      all ages were managed by observation rather than microsurgery or tendon transfers
      (p < 0.001). CONCLUSIONS: The authors' data indicate a general consensus in
      treatment choices for the two cases of microsurgical failure in infants with
      brachial plexus birth palsies as well as in satisfaction among experienced
      surgeons in using these treatments.

PMID- 16980860
TI  - Age-dependent closure of bony defects after frontal orbital advancement.
AB  - BACKGROUND: The ability of the immature skull to spontaneously heal large bony
      defects created after craniofacial procedures was examined over a 25-year period
      of craniofacial surgery at the Children's Hospital of Philadelphia. METHODS: Only
      patients who underwent frontal orbital advancement and reconstruction, had at
      least 1 year of documented follow-up, and had the presence or absence of a bony
      defect documented on clinical examination were included. The sex, age at
      operation, diagnosis, history of a prior craniectomy, and presence or absence of
      a postoperative infection were determined for each patient. A variety of
      statistics were applied to the data. RESULTS: Eighty-one patients met the
      inclusion criteria. A statistically significant association between age at
      operation and closure of bony defect was demonstrated. Children who closed a bony
      defect after frontal orbital advancement and reconstruction were significantly
      younger than those children who had a persistent bony defect. Iterative
      regression analyses demonstrated that a transition point between closure and the
      inability to close bony defects occurred between 9 and 11 months of age. Closure
      of bony defects was not statistically associated with sex, prior craniectomy, an
      FGFR mutation, or a postoperative infection in the regression analysis.
      CONCLUSIONS: Healing of bony defects after frontal orbital advancement and
      reconstruction is significantly related to age at initial operation, with a mean
      age for closure of less than 12 months. Between 9 and 11 months of age, a change
      occurs that results in an increasingly lower probability of bony defect closure;
      thus, all other considerations being equal, initial frontal orbital advancement
      and reconstruction would ideally take place before this occurs.

PMID- 16980861
TI  - Long-term stability and growth following unilateral mandibular distraction in
      growing children with craniofacial microsomia.
AB  - BACKGROUND: The purpose of this study was to evaluate long-term mandibular
      skeletal stability and growth following unilateral mandibular distraction in
      growing children. METHODS: This retrospective longitudinal study of 12
      consecutive patients with unilateral craniofacial microsomia who underwent
      mandibular distraction had a range of 5 years of postdistraction follow-up; five
      patients were followed for 10 years. Records included clinical photographs,
      dental study models, lateral and posteroanterior cephalograms, and panoramic
      radiographs obtained before distraction, at the time of device removal, and 1, 5,
      and 10 years after distraction. The mean patient age at the time of distraction
      was 48 months. The device was activated an average of 21.7 mm at the rate of 1 mm
      per day. The mean latency period was 6.1 days, and the mean consolidation period
      was 60.6 days. Fifty-two parameters were examined at each of the five time
      intervals. RESULTS: On average, the ramal length (condylion to gonion) increased
      13.04 mm in the distracted rami. At 1 year after distraction, this dimension
      decreased by 3.46 mm. At 5 and 10 years after distraction, the average condylion
      gonion dimension increased by 3.83 and 4 mm, respectively, with an average growth
      rate of 0.87 mm per year; during the same period, the unaffected ramus grew 1.15
      mm per year. CONCLUSIONS: The distraction technique does not eliminate the
      inherent growth potential of the affected mandibular side. Facial asymmetry is
      significantly improved after distraction, and despite mild relapse observed
      during the first year, surgical correction is stable in the later years of follow
      up.

PMID- 16980862
TI  - Cleft maxillary distraction versus orthognathic surgery: clinical morbidities and
      surgical relapse.
AB  - BACKGROUND: This is the first randomized controlled study aiming to compare the
      postoperative clinical morbidities in cleft lip and palate patients treated with
      distraction osteogenesis versus conventional orthognathic surgery. METHODS:
      Twenty-nine cleft lip and palate patients with moderate maxillary hypoplasia
      requiring a maxillary Le Fort I advancement of 4 to 10 mm were randomized into
      two groups for either internal maxillary distractors or immediate fragment
      transposition using miniplates and screw fixation. Clinical morbidities were
      recorded using standardized questionnaires. Skeletal and dental relapses were
      assessed using lateral cephalometric landmarks. RESULTS: In the distraction
      group, two of 15 patients developed infection around the distractors and one
      patient had an occlusal relapse. Among the 14 patients who received conventional
      orthognathic surgery, the complications included intraoperative hemorrhage (n =
      1), plate exposure leading to sinusitis (n = 1), and occlusal relapse (n = 1). In
      the skeletal relapses of the osteotomy group, a statistically significant
      vertical relapse of the A point was noted during the second to twelfth weeks when
      compared with the distraction group. A statistically significant horizontal
      relapse of the A and P points during the eighth to twelfth weeks was noted when
      the osteotomy group was compared with the distraction group. CONCLUSIONS: There
      were no major differences in the clinical morbidities between the osteotomy and
      distraction groups. Distraction provided better skeletal stability, whereas there
      was a significant amount of skeletal relapse in the first 12 weeks after
      conventional cleft maxillary osteotomy.

PMID- 16980864
TI  - Periorbital rejuvenation and the African American patient: a survey approach.
AB  - BACKGROUND: The number of African Americans pursuing cosmetic plastic surgery is
      increasing. Nonetheless, the authors postulate that the African American patients
      pursuing certain cosmetic procedures still have preconceived notions and concerns
      distinct from their Caucasian counterparts, thereby demanding a different
      surgical strategy. A questionnaire approach was used to determine the concerns,
      expectations, and desires of African American patients regarding periorbital
      rejuvenation and to compare these outcomes with those of Caucasian patients.
      METHODS: One hundred five African American female subjects and 30 Caucasian
      female subjects affiliated with the senior surgeon's cosmetic practice were
      contacted. Of these, 85 African American and 26 Caucasian subjects were
      administered a survey of 18 standardized questions. Patients were stratified in
      terms of age and race to dissect generational and ethnologic concepts toward
      oculoplastic surgery and features of the African American eyelid. The Caucasian
      subjects served as the control group. RESULTS: Of the African American subjects,
      85.9 percent had a favorable or neutral opinion of plastic surgery, and 72.9
      percent did not feel plastic surgery was exclusively for Caucasians. Nearly half
      of all African American subjects interviewed likened African American periorbital
      characteristics to those of Asians, whereas only 19.2 percent of Caucasian
      subjects acknowledged such similarities in African Americans. CONCLUSIONS: This
      study demonstrates the idea that a directed approach to blepharoplasty is
      necessary to help African American patients achieve their desire to maintain
      their ethnic identity while rejuvenating their appearance.

PMID- 16980865
TI  - Platelet gel sealant use in rhytidectomy.
AB  - BACKGROUND: A prospective study was used to evaluate the efficacy of a
      commercially available platelet gel product as a sealant to decrease postsurgical
      drain fluid rates and volumes in patients who have undergone rhytidectomy
      procedures. Quantitative assessments of postoperative drain fluid outputs were
      compared in subjects who did and did not receive platelet gel treatment. METHODS:
      Autologous platelet concentrate was prepared from each subject (n = 19), combined
      with bovine thrombin to form a platelet gel, and applied during the rhytidectomy
      procedure. Surgical drains were placed and effluent was collected postoperatively
      at 8-hour intervals for 24 hours and the volumes were recorded. A retrospective
      examination of surgical drain output over time in subjects (n = 14) who did not
      receive platelet gel treatment was performed; this group served as the control
      group. RESULTS: Subjects who received the platelet gel sealant treatment had
      significantly decreased surgical drain fluid levels over 24 hours [109 +/- 8.5 ml
      (mean +/- SEM)] compared with subjects who did not receive the platelet gel
      sealant (78 +/- 7.5 ml) (p < 0.02). From 0 to 8 hours postoperatively, platelet
      gel-treated subjects had a mean 35 percent decrease in fluid levels compared with
      the controls (p < 0.03). No difference in surgical drain outputs was observed
      from 8 to 16 hours between the two experimental groups. From 16 to 24 hours, the
      control group had increased mean fluid levels (20 percent) and the platelet gel
      sealant group output levels decreased (50 percent). CONCLUSIONS: Platelet gel
      sealant treatment was associated with decreased surgical fluid drain output in
      the first 24 hours postoperatively.

PMID- 16980866
TI  - An outcomes analysis of patients undergoing body contouring surgery after massive
      weight loss.
AB  - BACKGROUND: Although published reports about technical management of massive
      weight loss patients are beginning to appear, risk factors for complications
      following body contouring operations are not known. METHODS: A retrospective
      analysis of massive weight loss patients who had body contouring operations
      between March of 1998 and October of 2004 was performed. Demographic and surgical
      factors were analyzed. Outcome measures included seroma, wound dehiscence,
      thromboembolic complications, blood transfusion after surgery, and extended
      lengths of stay (>2 days). RESULTS: A total of 139 patients were analyzed; 82.7
      percent of them were female; mean age was 41 years. On multiple logistic
      regression, male gender was associated with significant risks for wound
      dehiscence (odds ratio, 6.4; p = 0.01). There were also trends toward increased
      risk for wound dehiscence with hypothyroidism (odds ratio, 4.3; p = 0.06) and
      Ehlers-Danlos syndrome (odds ratio, 18.7; p = 0.05). In terms of risk of blood
      transfusion, asthma and having three or more procedures were the two variables
      that emerged with significant association (odds ratio, 16.8 and 13.7,
      respectively; both p < 0.01). Increased length of stay to greater than 2 days was
      also significantly associated with having three or more procedures (odds ratio,
      4.72; p < 0.01). CONCLUSIONS: Male gender, hypothyroidism, and Ehlers-Danlos
      syndrome may be risk factors for wound dehiscence following body contour
      operations for massive weight loss. Asthma may be a marker of poor general health
      status, and asthmatic patients are at increased risk for requiring blood
      transfusions. Having three or more procedures is associated with an increased
      risk of blood transfusion and increased length of stay.

PMID- 16980867
TI  - A prospective, randomized, double-blind, controlled clinical trial comparing
      laser-assisted lipoplasty with suction-assisted lipoplasty.
AB  - BACKGROUND: The authors randomized and prospectively analyzed their clinical
      experience with the use of internal neodymium:yttrium-aluminum-garnet low-level
      laser-assisted lipoplasty compared with suction-assisted lipoplasty. METHODS:
      Suction-assisted lipoplasty was generated through a SmartLipo machine and
      delivered into the subcutaneous tissues through 2-mm solid optical probes.
      Ipsilateral suction-assisted lipoplasty and contralateral laser-assisted
      lipoplasty were performed on one or more comparable topographic areas of the body
      in the same patient. Laser-assisted lipoplasty and suction-assisted lipoplasty
      sides of 25 patients were compared with preoperative and postoperative
      photographs at 3 to 5 days, 12 to 15 days, and 6 to 11 months. Statistical
      analysis considered surgeon and patient satisfaction, time used in the
      procedures, learning curves, lipocrits, operative technique, postoperative pain,
      edema, ecchymosis, time of recovery, body mass index, DNA proteins, free fatty
      acids, and cytologic patterns of post-laser-assisted lipoplasty and suction
      assisted lipoplasty adipocyte architecture. Photographs were sent to the patients
      (blinded to the operated sides) and two plastic surgeons unfamiliar with the
      cases for evaluation of results. RESULTS: All patients completed the
      preestablished follow-ups. No complications were observed. Less pain, lower
      lipocrits, higher triglycerides, and DNA cellular membrane traces were detected
      in the laser-assisted lipoplasty sides. All other considerations studied showed
      no differences with either technique in the three periods of the follow-up
      controls. Cytologic studies showed more damage of the adipocytes in the laser
      assisted lipoplasty sides. CONCLUSIONS: No major clinical differences for suction
      assisted lipoplasty versus laser-assisted lipoplasty were found. Higher
      concentrations of free-fatty acids after laser-assisted lipoplasty must alert us
      to possible hepatic and renal toxicity.

PMID- 16980868
TI  - Role of adipokines in the obesity-inflammation relationship: the effect of fat
      removal.
AB  - During the past 10 years, there has been a dramatic increase in the prevalence of
      obesity in the United States and other developed nations. Recent studies indicate
      that adipose tissue is an endocrine organ producing numerous proteins,
      collectively referred to as adipokines, with broad biological activity, that play
      an important autocrine role in obesity-associated complications. Adipose tissue
      in general and visceral fat in particular are thought to be key regulators of
      inflammation. Inflammation is heavily involved in the onset and development of
      atherothrombotic disease. Moreover, chronic inflammation may also represent a
      triggering factor in the origin of the metabolic syndrome and type 2 diabetes
      mellitus. According to a hypothesis, stimuli such as overnutrition, physical
      inactivity, and aging would result in cytokine hypersecretion and eventually lead
      to insulin resistance and diabetes in genetically or metabolically predisposed
      individuals. This article discusses the current understanding of important
      adipokines thought to be involved in the metabolic and cardiovascular risk
      associated with obesity. Available evidence linking fat removal by liposuction to
      modification of cardiovascular risk and vascular inflammatory markers in the
      obese patient is also presented. Most studies have shown that liposuction
      produces beneficial effects on insulin resistance and vascular inflammation in
      the obese patient, reducing its cardiovascular risk. Besides having a significant
      role in body contouring of the obese patient at the end of the lengthy process of
      bariatric surgery and massive weight loss, plastic surgery should be incorporated
      into a multifaceted program of lifestyle changes that allows the obese patient to
      obtain weight loss and, more importantly, to maintain the reduced weight in the
      long term.

PMID- 16980870
TI  - Practice advisory on pain management and prevention of postoperative nausea and
      vomiting.

PMID- 16980871
TI  - Podcasts on the Plastic and Reconstructive Surgery Web Site: the journal goes
      portable and audio.

PMID- 16980872
TI  - Face transplantation: an extraordinary case with lessons for ordinary practice.

PMID- 16980874
TI  - Perfusion zones of the DIEP flap revisited: a clinical study.

PMID- 16980877
TI  - Key issues in advanced bleeding care in trauma.
AB  - The incidence of hemostatic abnormalities in the early hours after traumatic
      incident is high and represents an independent predictor of mortality. Key
      factors in the development of traumatic coagulopathy include the severity of
      injury, hypothermia, acidosis, hemorrhagic shock, hemodilution, clotting factor
      consumption, and fibrinolysis. Assessment of bleeding includes evaluation of the
      mechanism of injury, vital signs, biochemistry, detection of external and
      internal bleeding sources, injuries found upon secondary investigation, and
      response to treatment. Priority in treating the bleeding trauma patient should be
      given to prevention of further bleeding, hypothermia, acidosis, coagulopathy, and
      maintenance of tissue oxygenation, achieved by careful physical handling, damage
      control surgery, analgesia, maintenance of normothermia, correction of
      coagulopathy, control of blood pH, and serum calcium. Priority during initial
      treatment is to restore tissue perfusion and achieve hemostasis in vital
      functions; other nonvital procedures may generally be delayed. This state-of-the
      art review aims to address key issues in acute control of bleeding in the trauma
      patient.

PMID- 16980878
TI  - The future of therapeutic myocardial angiogenesis.
AB  - Despite improvements in its medical and surgical management, ischemic coronary
      disease remains responsible for significant morbidity, mortality, and economic
      burden in developed nations. Therapeutic myocardial angiogenesis is an attractive
      treatment option for patients with end-stage coronary disease who have failed
      percutaneous and surgical methods of revascularization. Over the past decade, our
      understanding of the biology of new blood vessel formation has improved
      significantly, and consequently, the use of growth factors to induce myocardial
      angiogenesis has been attempted in preclinical and clinical trials. Although
      growth factor therapy had demonstrated tremendous success in animal models,
      clinical trials have shown limited benefit in patients with coronary disease.
      Vascular endothelial growth factors and fibroblast growth factors are perhaps the
      most potent inducers of angiogenesis that have been used in animal models, and
      the only ones that have been used in clinical trials. This review outlines the
      biology of new vessel formation and the effects of these growth factors in the
      context of myocardial angiogenesis with an emphasis on the effects on the
      endothelium. It also provides a brief overview of delivery strategies and
      summarizes the preclinical and clinical evidence relating to exogenous growth
      factor delivery for myocardial angiogenesis. Lastly, we discuss the limitations
      and future challenges of angiogenic therapy.

PMID- 16980879
TI  - The effects of leukoreduced blood transfusion on infection risk following injury:
      a randomized controlled trial.
AB  - Allogeneic blood transfusions in surgical patients have been associated with an
      increased risk of infectious complications and organ dysfunction. Residual
      leukocytes contaminating units of packed red blood cells have been incriminated
      through the induction of anergy and/or a potentiated inflammatory response,
      leading to the possibility that leukoreduced red blood cell transfusion might
      mitigate these effects. We set out to evaluate the effect of leukoreduced red
      cell transfusion on the risk of infections complications in patients requiring
      transfusion following injury. We conducted a single-center, double-blinded
      randomized controlled trial of leukoreduced versus standard, nonleukoreduced red
      blood cell transfusions in injured patients receiving transfusion within 24 hrs
      of injury. The primary endpoint was infectious complications within 28 days of
      randomization. Secondary end points were multiple organ failure, length of stay,
      febrile episodes, and mortality. Two hundred sixty eight subjects were eligible
      for analysis. Rates of infectious complications were similar in subjects
      receiving leukoreduced transfusions (30%) or standard transfusions (36%) ([RR],
      0.84 [0.55-1.3]) and there was no statistically significant effect of
      leukoreduced blood transfusion on mortality [RR, 1.20 (0.74-1.9)], febrile
      episodes [RR, 1.01 (0.89-1.2)], or organ dysfunction scores (5.9 vs. 6.6;
      P=0.29). Thus, pre-storage leukoreduction of allogeneic red blood cells had a
      small, but non-significant effect on the rate of infectious complication in this
      high-risk population requiring transfusion. There was no effect on the rates of
      febrile episodes, mortality, length of stay, or severity of organ dysfunction.

PMID- 16980880
TI  - Children under 4 years are at greater risk of mortality following acute burn
      injury: evidence from a national sample of 12,902 pediatric admissions.
AB  - It is important to have an accurate understanding of mortality risk in children
      to make sound treatment decisions and to advise parents and families. Several
      studies have found that children younger than 4 years are at greater risk for
      mortality from burn injury than older children, although other studies have found
      no difference. All of these studies, however, have been limited by small sample
      sizes from single burn centers. The objective of this study was to assess age
      related mortality risk in a sample of more than 12,000 children from a national
      burn registry who were admitted to 43 burn centers in the United States from 1992
      to 2002. The study showed that, compared with older children, children younger
      than 4 years were significantly more likely to be admitted with scalds rather
      than flame burns, had smaller burn injuries, and were less likely to have an
      inhalation injury. Logistic regression analysis was used to assess age-related
      mortality risk. After adjusting for sex, burn size, inhalation injury, and type
      of burn (flame versus scald), the risk of mortality was substantially higher for
      children aged 0 to 1.9 years (odds ratio, 2.70; P<0.001) and for children aged
      2.0 to 3.9 years (odds ratio, 2.00; P<0.01) as compared with children aged 4
      years or older. This study provides strong evidence that when comparing children
      based on burn injuries of similar size and etiology, children younger than 4
      years are at substantial risk for death as compared with older children.

PMID- 16980881
TI  - A reappraisal of isoproterenol in goal-directed therapy of septic shock.
AB  - The goal of the study was to evaluate the effect of isoproterenol prescribed in
      goal-directed therapy for septic shock. Out of a cohort of 89 patients with
      septic shock, 14 patients treated with fluid and norepinephrine had inappropriate
      mixed venous oxygen saturation (SvO2<70%) not responding to correction of
      hypoxemia and anemia (>8 g.dL-1). Isoproterenol administration was started at a
      dose of 0.04 microg.kg-1.minute-1 with 0.025 microg.kg-1.minute-1 increments
      every 30 minutes until SvO2 was greater than 70%. Mean arterial pressure was
      maintained>or=65 mm.Hg by adjusting the norepinephrine infusion. Hemodynamic,
      oxygen, and renal variables were collected during a 12-h period. Patients with a
      known prior history of coronary disease were not eligible. Isoproterenol
      administration increased significantly SvO2 (62%+/-10% to 71%+/-9%), cardiac
      index (3.1+/-0.6 to 4.4+/-1.4 L.min-1.m-2), stroke index (27+/-3.4 to 38+/-6.1
      mL.m-2), and left ventricular stroke work index (24+/-3.4 to 40+/-5.0 g.m-1.m-2).
      Heart rate rise did not reach a significant level. Arterial lactate concentration
      decreased significantly during the study period (5.7+/-2.8 to 3.4+/-1.6 mmol.L
      1). No cardiac adverse events occurred with any electrocardiographic aspects of
      myocardial ischemia. This study suggests that isoproterenol is efficient to
      improve hemodynamics and oxygen variables in septic shock patients. There is a
      need for future investigations in larger groups of patients to determine whether
      isoproterenol can be an alternative to dobutamine.

PMID- 16980882
TI  - Stimulation of alpha7 nicotinic acetylcholine receptor inhibits CD14 and the toll
      like receptor 4 expression in human monocytes.
AB  - The lipopolysaccharide (LPS)-receptor complex, CD14/toll-like receptor 4, is
      known to play a role in the immune responses during sepsis. Excessive
      inflammation and tumor necrosis factor (TNF)-alpha synthesis have been reported
      to cause morbidity and mortality in endotoxemia and sepsis. Cell-to-cell
      interaction through the engagement between intercellular adhesion molecule 1,
      B7.1, and CD40 on monocytes and their ligands on T cells has been suggested to
      play a role in the inflammatory response such as TNF-alpha and interleukin 10
      production. Nicotine, with the stimulation of the nicotinic acetylcholine
      receptor alpha7 subunit (alpha7-nAChR), has now become the focus of attention
      because of its anti-inflammatory effects. However, little is known about the
      mechanism of the inhibitory effects induced by nicotine on the LPS-induced immune
      responses. In the present study, we found that nicotine suppressed the expression
      of CD14, toll-like receptor 4, intercellular adhesion molecule 1, B7.1, and CD40
      on monocytes and the production of TNF-alpha, but not interleukin 10, in human
      peripheral blood mononuclear cells in the presence of LPS. The actions of
      nicotine were reversed by a nonselective and a selective alpha7-nAChR antagonist,
      mecamylamine and alpha-bungarotoxin, respectively. Therefore, nicotine might
      inhibit the LPS receptor complex expression via alpha7-nAChR, thus leading to a
      decrease in the adhesion molecule expression and TNF-alpha production. Moreover,
      we demonstrated that a nuclear factor-kappaB and a p38 mitogen-activated protein
      kinase inhibitor mimicked the actions of nicotine in the presence of LPS. These
      results suggested that the nuclear factor-kappaB and p38 mitogen-activated
      protein kinase might be involved in the actions of nicotine.

PMID- 16980883
TI  - Protection against Pseudomonas aeruginosa pneumonia and sepsis-induced lung
      injury by overexpression of beta-defensin-2 in rats.
AB  - Beta-defensin-2 (BD-2), a small cationic antimicrobial peptide, was first
      described to be an inducible defensin at the epithelial surfaces. In vitro
      studies have demonstrated that it may play a pivotal role in the anti
      inflammatory immune response in addition to its antimicrobial activity. The
      purpose of this study was to evaluate the effect of overexpression of BD-2 on
      lung injury to crudely investigate whether the function of BD-2 in the lung
      attributed to both antimicrobial action and modulation of the immune response.
      Recombinant adenovirus carrying an expression cassette of rat BD-2 or control
      adenovirus carrying empty vector was administered intratracheally to Sprague
      Dawley rats 48 h before performing acute lung injury, which was induced either by
      Pseudomonas aeruginosa infection or by cecal ligation and double puncture (2CLP).
      In vivo antimicrobial activity of BD-2, histological changes of the lungs in both
      infectious and 2CLP models, pulmonary intracellular adhesion molecule-1 protein
      level, as well as the 7-day survival rate in the latter model were determined.
      Amounts of the P. aeruginosa in the lung with BD-2 overexpression were
      significantly lower compared with that in controls (2.87+/-0.76x10(4) colony
      forming units [CFU]/mL vs. 2.49+/-0.74x10(6) CFU/mL, P<0.05). Overexpression of
      BD-2 reduced alveolar damage, interstitial edema, and infiltration of neutrophils
      in both models. Furthermore, in the 2CLP model, recombinant BD-2 not only
      significantly decreased protein levels of intracellular adhesion molecule-1 in
      lung tissue at 24, 36, and 72 h after 2CLP (P<0.05), but also significantly
      improved the survival of rats (P<0.05). The CFU of abdominal bacteria was
      comparable to that in the control rats (P>0.05). Therefore, overexpression of BD
      2 protects against P. aeruginosa pneumonia and 2CLP-induced lung injury based on
      its antimicrobial and anti-inflammatory activities, respectively. Modulating the
      expression level of BD-2 may serve as an approach to attenuate lung injury.

PMID- 16980884
TI  - Differential contribution of N-methyl-D-aspartate and non-N-methyl-D-aspartate
      receptors in the intermediolateral cell column of the thoracic spinal cord to
      sympathetic vasomotor tone during experimental endotoxemia in the rat.
AB  - Although the rostral ventrolateral medulla maintains neurogenic vasomotor tone
      via glutamatergic excitation to sympathetic preganglionic neurons located at the
      intermediolateral cell column (IML) of thoracic spinal cord, the relative
      contribution of N-methyl-d-aspartate (NMDA) and non-NMDA receptors on IML neurons
      at rest or during endotoxemia remain unknown. The present study addressed this
      issue using a combination of physiological, pharmacological, and double
      immunofluorescence approaches. Adult male Sprague-Dawley rats maintained under
      propofol anesthesia were used. Intrathecal administration of equimolar
      concentrations (75, 150, or 300 nmol) of an NMDA antagonist, dizocilpine (MK801),
      or a non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, into T10 to T12
      spinal cord elicited a reduction in resting vasomotor tone that was comparable in
      time course and in magnitude. Although both glutamate receptor antagonists
      exacerbated mortality and potentiated the elicited hypotension, bradycardia, or
      reduction in vasomotor tone during experimental endotoxemia induced by
      intravenous administration of Escherichia coli lipopolysaccharide (30 mg kg-1;
      results comparable to 6-cyano-7-nitroquinoxaline-2,3-dione at 150 nmol) were
      obtained only when MK801 was given at 300 nmol. Confocal microscopy further
      showed that augmented immunoreactivity of NR1 subunit on IML neurons coincided
      with the phase of endotoxemia when vasomotor tone was augmented; GluR1
      immunoreactivity remained stable throughout experimental endotoxemia. These
      findings suggest that NMDA and non-NMDA receptors on IML neurons contribute to
      the generation of resting sympathetic vasomotor tone. However, up-regulation of
      NMDA receptors on IML neurons plays a crucial role in the maintenance of
      vasomotor tone during endotoxemia.

PMID- 16980885
TI  - The immediate response to severe shock in a canine model with a combination of
      hypertonic-hyperoncotic solution with naloxone.
AB  - To evaluate the acute hemodynamic and acid-base balance effects of hypertonic
      hyperoncotic solution (HHS) combined with naloxone in the treatment of
      hemorrhagic shock in 45 male splenectomized adult mongrel dogs, a severe
      controlled hemorrhagic shock (20 mmHg mean arterial pressure during 30 min) was
      established in the groups (n=6) no treatment, shed blood reinfusion, hypertonic
      hyperoncotic (saline-dextran) solution alone, naloxone alone (NX), or
      combination. Interventions included propiopromazine-pentobarbital anesthesia and
      installation of Swan-Ganz, femoral arterial, and urethral catheters, and
      exsanguination at 20 mmHg mean arterial pressure during 30 min followed by
      treatment and observation for 160 min. Fifteen (33%) dogs died before completing
      the 30-min shock period. Another 33% from the no-treatment group died during the
      following 90 min. Shed blood improved the cardiac index, arterial pressure, and
      acid-base balance. NX restored the cardiac index to less than 60% of baseline and
      reduced vascular resistance. Additionally, NX produced no improvement in
      acidosis, with 1 dog dead at 95 min posttreatment. HHS restored the cardiac index
      for 45 min and increased vascular resistance and arterial pressure. Acidosis was
      not improved. Single-dose HHS combined with naloxone resulted in a high cardiac
      index, oxygen consumption, and urine output with low peripheral vascular
      resistance (and no acute mortality) compared with untreated or single-dose
      groups.

PMID- 16980886
TI  - Essential role for platelets in organ injury and inflammation in resuscitated
      hemorrhagic shock.
AB  - Platelets are known to contribute to ischemia/reperfusion in several organs, but
      their role in inflammation and organ injury after hemorrhagic shock (HS) has not
      been examined. To address this issue, we rendered mice thrombocytopenic (20% of
      normal platelet count) by treatment with pOp3, a rat monoclonal antibody against
      platelet glycoprotein Ibalpha, 24 h before subjecting them to either a standard
      HS or sham protocol. Liver apoptosis increased 3- to 5-fold (P<0.05), and focal
      liver necrosis increased 11-fold (P<0.01) in placebo-treated shock mice compared
      with sham; these increased indices of liver injury were completely prevented by
      pOp3 pretreatment. Neutrophils infiltrating the liver increased nearly 3-fold in
      placebo-treated shock mice versus sham (P<0.05); this shock-induced increase in
      neutrophil infiltration was also eliminated by pretreatment with pOp3. Alveolar
      cross-sectional area, used to histologically assess interstitial lung edema and
      cellular infiltration, was reduced by 25% in pOp3-treated shock mice versus
      placebo-treated shock mice (P<0.05). Similar to the results in liver, pOp3
      pretreatment decreased neutrophil infiltration in the lung after HS. Thus,
      platelets contribute to the inflammatory injuries of the liver and lung after HS,
      in part, perhaps by facilitating neutrophil infiltration into tissues.

PMID- 16980887
TI  - Assessing intravascular volume by difference in pulse pressure in pigs submitted
      to graded hemorrhage.
AB  - We assessed changes in intravascular volume monitored by difference in pulse
      pressure (dPP%) after stepwise hemorrhage in an experimental pig model. Six pigs
      (23-25 kg) were anesthetized (isoflurane 1.5 vol%) and mechanically ventilated to
      keep end-tidal CO2 (etCO2) at 35 mmHg. A PA-catheter and an arterial catheter
      were placed via femoral access. During and after surgery, animals received
      lactated Ringer's solution as long as they were considered volume responders
      (dPP>13%). Then animals were allowed to stabilize from the induction of
      anesthesia and insertion of catheters for 30 min. After stabilization, baseline
      measurements were taken. Five percent of blood volume was withdrawn, followed by
      another 5%, and then in 10%-increments until death from exsanguination occurred.
      After withdrawal of 5% of blood volume, all pigs were considered volume
      responders (dPP>13%); dPP rose significantly from 6.1+/-3.3% to 19.4+/-4.2%. The
      regression analysis of stepwise hemorrhage revealed a linear relation between
      blood loss (hemorrhage in %) and dPP (y=0.99*x+14; R2=0.7764; P<.0001). In
      addition, dPP was the only parameter that changed significantly between baseline
      and a blood loss of 5% (P<0.01), whereas cardiac output, stroke volume, heart
      rate, MAP, central venous pressure, pulmonary artery occlusion pressure, and
      systemic vascular resistance, respectively, remained unchanged. We conclude that
      in an experimental hypovolemic pig model, dPP correlates well with blood loss.

PMID- 16980888
TI  - Effects of hemorrhage and lactated Ringer's resuscitation on coagulation and
      fibrinogen metabolism in swine.
AB  - Hemorrhagic coagulopathy is a significant complication after traumatic injury,
      and much of the underlying mechanism remains unclear. We investigated the changes
      in fibrinogen metabolism and coagulation after a moderate hemorrhage and
      resuscitation. Pigs of either sex (weight, 40.9+/-0.8 kg) were anesthetized and
      instrumented with arterial and venous catheters and a thermodilution cardiac
      output catheter. Pigs were randomized into control (C; n=6), hemorrhage (H; n=6),
      and hemorrhage and resuscitation (H-LR; n=6) groups. Hemorrhage was induced by
      bleeding 35% of total blood volume for 30 min in H and H-LR groups. Resuscitation
      in H-LR group was performed using lactated Ringer's solution (LR) at 3 times the
      bled volume for 30 min. Fibrinogen metabolism was quantified using a primed
      constant infusion of 1-13C-phenylalanine (6 h) and d5-phenylalanine (4 h) and
      subsequent analysis by gas chromatograph-mass spectrometry, together with
      measurements of hemodynamics (hourly) and coagulation by thromboelastography (at
      baseline and 4 h after hemorrhage and resuscitation). Hemorrhage caused decreases
      in arterial pH and base excess, and an increase in arterial lactate content.
      Fluid resuscitation corrected these changes toward normal levels. Fibrinogen
      level was unchanged in C and decreased to 76%+/-4% in H and to 73%+/-3% in H-LR
      (both P<0.05, compared with baseline) after hemorrhage and resuscitation.
      Fibrinogen breakdown was increased from 3.0+/-0.4 mg kg-1 h-1 in C to 5.4+/-0.6
      mg kg-1 h-1 in H and to 5.6+/-0.5 mg kg-1 h-1 in H-LR (both P<0.05, compared with
      control), but synthesis was unchanged. The clotting reaction time was unchanged
      in C and shortened to 93%+/-3% in H and to 91%+/-1% in H-LR (both P<0.05,
      compared with baseline). We conclude that hemorrhagic shock caused accelerated
      fibrinogen breakdown and coagulation. The LR resuscitation reduced tissue hypoxia
      indexes but did not affect the changes in fibrinogen metabolism and coagulation
      from hemorrhage. Thus, effective treatment of hemorrhage should include combining
      standard-of-care resuscitation with interventions to correct alterations in
      coagulation.

PMID- 16980889
TI  - Green tea polyphenol extract attenuates zymosan-induced non-septic shock in mice.
AB  - Multiple-organ failure (MOF) is defined as the progressive deterioration in
      function which occurs in several organs or systems in patients with septic shock,
      multiple trauma, severe burns, or pancreatitis. In the present study, we have
      investigated the effects of Green Tea extract (GTE) on the development of general
      inflammation caused by zymosan (500 mg/kg, administered i.p. as a suspension in
      saline) in mice. Organ failure and systemic inflammation in mice was assessed 18
      hours after administration of zymosan and/or GTE and monitored for 12 days (for
      loss of body weight and mortality). Treatment of mice with GTE (25 mg/kg i.p., 1
      and 6 hours after zymosan) attenuated the peritoneal exudation and the migration
      of polymorphonuclear cells (PMNs) caused by zymosan, GTE also attenuated the
      lung, liver and pancreatic injury and renal dysfunction caused by zymosan as well
      as the increase in myeloperoxidase (MPO) activity caused by zymosan in the lung
      and intestine. Immunohistochemical analysis for inducible nitric oxide synthase
      (iNOS), nitrotyrosine and poly(ADP-ribose) (PAR) revealed positive staining in
      lung and intestine tissues obtained from zymosan-treated mice. The degree of
      staining for nitrotyrosine, iNOS and PAR were markedly reduced in tissue sections
      obtained from zymosan-treated mice, which received GTE. In conclusion this study
      provides evidence, for the first time, that GTE attenuates the degree of zymosan
      induced generalized inflammation in mice.

PMID- 16980890
TI  - Oleuropein: a novel immunomodulator conferring prolonged survival in experimental
      sepsis by Pseudomonas aeruginosa.
AB  - Oleuropein, a novel immunomodulator derived from olive tree, was assessed in
      vitro and in experimental sepsis by Pseudomonas aeruginosa. After addition in
      monocyte and neutrophil cultures, malondialdehyde, TNF-alpha, IL-6, and bacterial
      counts were estimated in supernatants. Acute pyelonephritis was induced in 70
      rabbits after inoculation of pathogen in the renal pelvis. Intravenous therapy
      was administered in four groups postchallenge by one multidrug-resistant isolate
      (A, controls; B, oleuropein; C, amikacin; D, both agents) and in three groups
      postchallenge by one susceptible isolate (E, controls; F, oleuropein; G,
      amikacin). Survival was recorded; bacterial growth in blood and organs was
      counted; endotoxins (LPS), malondialdehyde, total antioxidant status, and TNF
      alpha in serum were estimated. TNF-alpha and IL-6 of cell supernatants were not
      increased compared with controls when triggered by LPS and P. aeruginosa. Counts
      of multidrug-resistant P. aeruginosa were decreased in monocyte supernatants.
      Median survival of groups A, B, C, D, E, F, and G were 3.00, 6.00, 2.00, 10.00,
      1.00, 5.00, and 1.00 days, respectively. Bacteria in blood were lower at 48 h in
      groups B and D compared with A and in groups F and G compared with E. Total
      antioxidant status decreased steadily over time in groups A, C, D, and G, but not
      in groups B and F. TNF-alpha of groups B, C, and D was lower than A at 48 h.
      Tissue bacteria decreased in group F compared with E. Oleuropein prolonged
      survival in experimental sepsis probably by promoting phagocytosis or inhibiting
      biosynthesis of proinflammatory cytokines.

PMID- 16980891
TI  - Bacterial clearance and mortality are not improved by a combination of IL-10
      neutralization and IFN-gamma administration in a murine model of post-CLP
      immunosuppression.
AB  - Immunocompromise after a major injury is presumed to be a predisposing factor for
      sepsis. Mice subjected to sublethal cecal ligation and puncture (CLP) and
      challenged 5 days later with Pseudomonas aeruginosa had more bacterial growth in
      lung tissue, lower serum interferon gamma (IFN-gamma) and interleukin (IL) 12,and
      higher serum IL-10 when compared with sham CLP mice challenged with Pseudomonas.
      To test the functional significance of these alterations in cytokine production
      in the immune response to bacteria, we administered IFN-gamma and anti-IL-10 to
      post-CLP mice before the Pseudomonas challenge. Administration of IFN-gamma and
      anti-IL-10 did not improve bacterial clearance or mortality in post-CLP mice. In
      further studies, we administered IFN-gamma to IL-10 knockout mice before a
      challenge with P. aeruginosa. Our results showed no significant differences in
      bacterial clearance or mortality in IL-10 knockout mice with or without IFN-gamma
      treatment compared with wild-type controls. Finally, because most mortality
      occurred within 2 to 3 days of the Pseudomonas challenge in the aforementioned
      studies and was likely associated with a marked proinflammatory response, we
      investigated the effect of IFN-gamma and anti-IL-10 on clearance of Pseudomonas
      in C3H/HeJ mice, which do not mount an exaggerated proinflammatory response to
      endotoxin or Gram-negative bacteria. Neither clearance of the Pseudomonas
      bacteria nor mortality was improved in C3H/HeJ mice receiving anti-IL-10 and IFN
      gamma. These results suggest that the suppressed IFN-gamma and IL-12 responses,
      in combination with an exaggerated IL-10 response to P. aeruginosa challenge
      after injury, do not correlate with bacterial clearance or survival.

PMID- 16980892
TI  - Accuracy of cut-off acetabular reamers for minimally invasive THA.
AB  - Cut-off reamers have been introduced for minimally invasive hip replacement to
      make reamer insertion through the small incision easier. However, the accuracy of
      cut-off reamers in comparison to traditional hemispherical reamers has not been
      documented. We reamed four human cadaveric hips using a cut-off reamer and three
      hips using a standard reamer. We started with smallest size reamer to remove
      subchondral bone, and the size was progressively increased until breaching the
      acetabular floor. We performed computed tomography scans for each reamer size to
      digitally determine the true dimensions and sphericity of the reamed acetabula.
      The cut-off reamers breached the acetabulum at a smaller size than with a
      standard reamer in two specimens, and at the same size as the standard reamer in
      one specimen. The accuracy of each reamer size was determined by quantifying the
      percentage of the reamed acetabular surface that was within 0.5 mm of the
      hemispherical reamer size. The average accuracy of the cut-off reamers was 70%
      compared with 81% for the standard reamers. The cut-off acetabular reamers showed
      a trend toward decreased accuracy that may be attributable to a tendency of the
      reamer to wobble in use.

PMID- 16980893
TI  - A new patellofemoral scoring system for total knee arthroplasty.
AB  - Patellofemoral complications after total knee arthroplasty (TKA) can result in
      substantial dissatisfaction with the procedure for some patients. In assessing
      outcomes of TKA, however, there is often a discrepancy between patellofemoral
      symptoms and the results obtained by conventional scoring and radiographic
      analysis. We asked whether a new scoring system and weightbearing radiographic
      view would more accurately represent patellofemoral kinematics and explain
      related complications. Sixty-nine patients (100 knees) who underwent posterior
      stabilized TKA between 1994 and 1997 were included for clinical and radiographic
      evaluation. A new patella score was developed to rapidly determine complications,
      ranged from 0 to 100 points, and included ratings for subjective and objective
      aspects of TKA. A new weight-bearing axial radiographic view was devised by
      positioning the standing patient in a semisquatted position. Measurements for
      patella alignment (tilt and subluxation) were performed. Preoperative Knee
      Society knee and function scores were 43 +/- 5 points, and 39 +/- 15 points,
      respectively. Postoperatively, scores increased to 93 +/- 8 and 89 +/- 8 points,
      respectively. The patella score averaged 89 +/- 8 points and showed satisfactory
      interobserver variability. The new weightbearing radiographic view demonstrated
      sources of patellofemoral symptoms. We report a new scoring system and
      weightbearing view that are easy to use and more accurately represent
      patellofemoral kinematics than do conventional methods of analysis.

PMID- 16980894
TI  - The progression of patellofemoral arthrosis after medial unicompartmental
      replacement: results at 11 to 15 years.

PMID- 16980895
TI  - Tibiofemoral contact behavior is improved in high-flexion cruciate retaining TKA.
AB  - Recently, total knee arthroplasty (TKA) designs have been modified to prevent
      edge loading on the posterior tibial articular surface and increase the
      tibiofemoral contact area at high degrees of flexion. The expected improvement in
      contact behavior of high-flexion TKA over conventional design is not well
      documented. We ascertained peak contact locations and contact areas of a
      conventional and a high-flexion cruciate-retaining TKA design. Both TKAs showed
      similar kinematics throughout the range of flexion although their contact
      behaviors differed: the peak contact point for the high-flexion TKA was located
      more anteriorly than the conventional TKA for flexion angles greater than 90
      degrees. The tibiofemoral contact of both TKAs reached the polyethylene posterior
      edge at 150 degrees. The contact on conventional TKA reached the polyethylene
      posterior edge approximately 15 degrees to 30 degrees before the high-flexion
      TKA. The high flexion TKA exhibited similar contact areas to conventional TKA.
      While the clinical relevance is unclear, these data suggest high flexion TKA
      might improve tibiofemoral contact biomechanics if high flexion is achievable.

PMID- 16980896
TI  - Mechanical characteristics of cortical bone pins designed for fracture fixation.
AB  - Pins constructed from cortical bone may provide a reasonable alternative to other
      fracture-fixation devices by circumventing some of the complications associated
      with stainless steel and synthetic biodegradable implants. However, it is unknown
      whether cortical bone pins provide comparable strength compared to conventional
      pins. Using four-point bending, we compared the mechanical characteristics of 1.2
      mm allogeneic cortical bone pins milled from specific regions of human tibiae and
      femora to commercially available 1.1-mm diameter stainless steel pins and 1.3-mm
      diameter polydioxanone pins. We used impact testing to identify mechanical
      differences in cortical bone pins between gender and harvest site. Cortical bone
      pins had better mechanical properties in four-point bending compared with
      polydioxanone pins, but not stainless steel pins. Pins milled from the right
      tibiae of males had the best bending characteristics. The mechanical performance
      of 1.2-mm cortical bone pins was comparable to those of stainless steel and
      polydioxanone pins regardless of site, bone, and gender. The clinical
      investigation of cortical bone pins as an implant for fracture fixation is
      warranted based on mechanical testing and comparison to commercially available
      polydioxanone and stainless steel pins.

PMID- 16980897
TI  - Bilateral femoral fatigue fracture: an unusual fracture in a military recruit.
AB  - We present a case report of a military recruit who had bilateral fatigue
      fractures of the distal femur. Possible predisposing factors and the long-term
      outcome of these unusual stress fractures also are presented. A 19-year-old
      recruit experienced knee pain 2 weeks after starting his military service.
      Bilateral nondisplaced transverse fatigue fractures were detected
      radiographically in the supracondylar region on the right side and in the distal
      1/3 of the femoral shaft on the left side. The fractures were treated with
      plaster casts for 5 weeks and healed properly. Osteopenia was seen in further
      examinations. At followup after 31 months followup the patient had fully resumed
      his previous athletic activity level and was symptom-free. Osteopenia still could
      be detected at the final examination. Nonoperative treatment with careful
      followup resulted in a favorable outcome in the nondisplaced bilateral distal
      fatigue femoral fractures in this patient.

PMID- 16980898
TI  - Shoulder arthroplasty versus hip and knee arthroplasties: a comparison of
      outcomes.
AB  - Although outcomes of shoulder, hip, and knee arthroplasties have been well
      described, there have been no studies directly comparing the outcomes of these
      procedures as treatments for osteoarthritis. We compared the inpatient mortality,
      complications, length of stay, and total charges of patients who had shoulder
      arthroplasty for osteoarthritis with those of patients who had hip and knee
      arthroplasties for osteoarthritis. A review of the Maryland Health Services Cost
      Review Commission discharge database identified 994 shoulder arthroplasties,
      15,414 hip arthroplasties, and 34,471 knee arthroplasties performed for
      osteoarthritis from 1994 to 2001. There were no in-hospital deaths after shoulder
      arthroplasty, whereas 27 (0.18%) and 54 (0.16%) deaths occurred after hip and
      knee arthroplasties, respectively. Compared with patients who had hip or knee
      arthroplasties, patients who had shoulder arthroplasties had, on average, a lower
      complication rate, a shorter length of stay, and fewer total charges. The latter
      had 1/2 as many in-hospital complications, were 1/6 as likely to have a length of
      stay 6 days or greater, and were 1/10 as likely to be charged more than $15,000.
      We believe shoulder arthroplasty is as safe as the more commonly performed major
      joint arthroplasties.

PMID- 16980899
TI  - Multiple ipsilateral lower extremity masses in a 46-year-old man.
      Schwannomatosis.

PMID- 16980901
TI  - Autologous chondrocyte implantation: superior biologic properties of hyaline
      cartilage repairs.
AB  - Information regarding the quality of autologous chondrocyte implantation repair
      is needed to determine whether the current autologous chondrocyte implantation
      surgical technology and the subsequent biologic repair processes are capable of
      reliably forming durable hyaline or hyaline-like cartilage in vivo. We report and
      analyze the properties and qualities of autologous chondrocyte implantation
      repairs. We evaluated 66 autologous chondrocyte implantation repairs in 57
      patients, 55 of whom had histology, indentometry, and International Cartilage
      Repair Society repair scoring at reoperation for mechanical symptoms or pain.
      International Knee Documentation Committee scores were used to address clinical
      outcome. Maximum stiffness, normalized stiffness, and International Cartilage
      Repair Society repair scoring were higher for hyaline articular cartilage repairs
      compared with fibrocartilage, with no difference in clinical outcome.
      Reoperations revealed 32 macroscopically abnormal repairs (Group B) and 23 knees
      with normal-looking repairs in which symptoms leading to arthroscopy were
      accounted for by other joint disorders (Group A). In Group A, 65% of repairs were
      either hyaline or hyaline-like cartilage compared with 28% in Group B. Autologous
      chondrocyte repairs composed of fibrocartilage showed more morphologic
      abnormalities and became symptomatic earlier than hyaline or hyaline-like
      cartilage repairs. The hyaline articular cartilage repairs had biomechanical
      properties comparable to surrounding cartilage and superior to those associated
      with fibrocartilage repairs.

PMID- 16980902
TI  - The cellular and molecular biology of periprosthetic osteolysis.
AB  - The generation of prosthetic implant wear after total joint arthroplasty is
      recognized as the major initiating event in development of periprosthetic
      osteolysis and aseptic loosening, the leading complication of this otherwise
      successful surgical procedure. We review current concepts of how wear debris
      causes osteolysis, and report ideas for prevention and treatment. Wear debris
      primarily targets macrophages and osteoclast precursor cells, although
      osteoblasts, fibroblasts, and lymphocytes also may be involved. Molecular
      responses include activation of MAP kinase pathways, transcription factors
      (including NFkappaB), and suppressors of cytokine signaling. This results in up
      regulation of proinflammatory signaling and inhibition of the protective actions
      of antiosteoclastogenic cytokines such as interferon gamma. Strategies to reduce
      osteolysis by choosing bearing surface materials with reduced wear properties
      should be balanced by awareness that reducing particle size may increase biologic
      activity. There are no approved treatments for osteolysis despite the promise of
      therapeutic agents against proinflammatory mediators (such as tumor necrosis
      factor) and osteoclasts (bisphosphonates and molecules blocking receptor
      activator of NFkappaB ligand [RANKL] signaling) shown in animal models.
      Considerable efforts are underway to develop such therapies, to identify novel
      targets for therapeutic intervention, and to develop effective outcome measures.

PMID- 16980903
TI  - Habitual floor activities increase risk of knee osteoarthritis.
AB  - Knee osteoarthritis is a major worldwide public health problem. Mechanical
      factors generally are considered important in its pathogenesis. Whether floor
      activities increase the risk of knee osteoarthritis is unclear. We performed a
      population-based survey to document the association of floor activities with
      pattern and severity of knee osteoarthritis. We identified 288 women and 288 men
      40 years or older from Songkhla province in southern Thailand. We recorded their
      lifetime histories of four common positions in floor activities: squatting,
      lotus, side-knee bending, and kneeling. Involvement of osteoarthritis was
      categorized in three patterns: isolated patellofemoral, isolated tibiofemoral,
      and combined. We used multinomial logistic regression analysis adjusted for age,
      gender, body mass index, and smoking status to identify associations between
      lifetime floor activity and knee osteo-arthritis. Squatting and side-knee bending
      positions increased the relative risk of radiographic knee osteoarthritis. All
      types of floor activities except kneeling increased the risk of moderate to
      severe radiographic knee osteoarthritis. Squatting and lotus positions increased
      the relative risk of knee pain with radiographic osteoarthritis. Our data suggest
      habitual lifetime squatting, lotus, and side-knee bending positions increase the
      risk of knee osteoarthritis.

PMID- 16980904
TI  - Body composition changes during lactation in HIV-infected and HIV-uninfected
      South African women.
AB  - BACKGROUND: The nutritional consequences of HIV infection in lactating women are
      unknown. OBJECTIVE: To measure the body composition of South African lactating
      women in relation to HIV status. METHODS: Fat-free mass (FFM) and fat mass (FM)
      using bioimpedance spectrometry (BIS) and anthropometric measurements were
      obtained at 8 and 24 weeks postpartum in 92 HIV-infected (HIVpos) and 50 HIV
      uninfected (HIVneg) lactating mothers. RESULTS: At 8 weeks, HIVpos and HIVneg
      mothers were not significantly different in height (159.7 vs. 158.9 cm), weight
      (62.7 vs. 63.9 kg), body mass index (BMI; 24.6 vs. 25.3 kg/m), FFM (40.7 vs. 42.8
      kg), or FM (21.6 vs. 22.0 kg), respectively. In HIVpos women, the median CD4
      count was 621 (range: 101-1585) cells/muL; 95% had CD4 counts >200 cells/muL.
      Between 8 and 24 weeks, HIVpos mothers had a mean weight loss of 1.4 kg in
      contrast to a 0.4-kg weight gain in HIVneg mothers (P < 0.01). There were no
      significant group differences with regard to change in FFM (0.3 vs. 0.1 kg; P =
      0.9) and FM (-1.5 vs. -0.3 kg; P = 0.2). CONCLUSION: HIVpos South African breast
      feeding mothers without severe immune suppression lost weight and subcutaneous
      fat between 8 and 24 weeks postpartum, whereas HIVneg mothers gained weight. FFM
      was maintained postpartum in HIVpos and HIVneg mothers.

PMID- 16980905
TI  - Incidence of metabolic syndrome in a cohort of HIV-infected adults and prevalence
      relative to the US population (National Health and Nutrition Examination Survey).
AB  - BACKGROUND: Metabolic syndrome increases the risk of cardiovascular outcomes and
      type II diabetes. Most of the metabolic abnormalities defining metabolic syndrome
      are observed in HIV. OBJECTIVE: To determine the incidence and risk factors for
      metabolic syndrome in HIV-infected adults in the Nutrition for Healthy Living
      (NFHL) study (2000-2003) and prevalence relative to the findings of the National
      Health and Nutrition Examination Survey (NHANES) (1999-2002). METHODS: Metabolic
      syndrome is > or =3 of the following: hypertriglyceridemia, low high-density
      lipoprotein (HDL) cholesterol, hypertension, abdominal obesity, and high serum
      glucose. The baseline prevalence of metabolic syndrome in the NFHL study (n =
      477) was compared to that in the NHANES (n = 1876), adjusted for age, race,
      gender, poverty, exercise, and diet. RESULTS: Almost one quarter of NFHL subjects
      had metabolic syndrome. Most with metabolic syndrome (77%) had low HDL and
      hypertriglyceridemia plus > or =1 additional abnormality. The prevalence of
      metabolic syndrome was significantly lower in HAART and non-HAART users compared
      with NHANES participants unadjusted for body mass index (BMI). After adjustment
      for BMI, it was no longer significant but the trend remained. The incidence of
      metabolic syndrome in the NFHL study was higher with increasing viral load,
      higher BMI, higher trunk-to-limb fat ratio, and Kaletra (lopinavir/ritonavir) or
      didanosine (ddI) use and lower among college-educated persons. CONCLUSIONS:
      Metabolic syndrome is mostly diagnosed through low HDL and high triglycerides in
      HIV. The risk of developing the syndrome is related to HIV, specific medications,
      and body fat.

PMID- 16980906
TI  - The economic burden of HIV in the United States in the era of highly active
      antiretroviral therapy: evidence of continuing racial and ethnic differences.
AB  - BACKGROUND: Assessing the economic burden of HIV/AIDS can help to quantify the
      effect of the epidemic on a population and assist policy makers in allocating
      public health resources. OBJECTIVE: To estimate the economic burden of HIV/AIDS
      in the United States and provide race/ethnicity-specific estimates. METHODS: We
      conducted an incidence-based cost-of-illness analysis to estimate the lifetime
      cost of HIV/AIDS resulting from new infections diagnosed in 2002. Data from the
      HIV/AIDS Reporting System of the Centers for Disease Control and Prevention were
      used to determine stage of disease at diagnosis and proportion of cases by
      race/ethnicity. Lifetime direct medical costs and mortality-related productivity
      losses were estimated using data on cost, life expectancy, and antiretroviral
      therapy (ART) use from the literature. RESULTS: The cost of new HIV infections in
      the United States in 2002 is estimated at $36.4 billion, including $6.7 billion
      in direct medical costs and $29.7 billion in productivity losses. Direct medical
      costs per case were highest for whites ($180,900) and lowest for blacks
      ($160,400). Productivity losses per case were lowest for whites ($661,100) and
      highest for Hispanics ($838,000). In a sensitivity analysis, universal use of ART
      and more effective ART regimens decreased the overall cost of illness.
      CONCLUSION: Direct medical costs and productivity losses of HIV/AIDS resulting
      from infections diagnosed in 2002 are substantial. Productivity losses far
      surpass direct medical costs and are disproportionately borne by minority
      races/ethnicities. Our analysis underscores economic benefits of more effective
      ART regimens and universal access to ART.

PMID- 16980907
TI  - Safety and acceptability of the candidate microbicide Carraguard in Thai Women:
      findings from a Phase II Clinical Trial.
AB  - OBJECTIVE: To determine the safety and acceptability of vaginal application of
      Carraguard, a carrageenan-derived candidate microbicide gel. DESIGN: A
      randomized, placebo-controlled, triple-blinded clinical trial was conducted in
      Chiang Rai, northern Thailand. METHODS: Women were asked to insert one applicator
      of study gel vaginally at least three times per week (with or without sex) and to
      use gel with condoms every time they had sex. Safety was assessed by visual
      inspection of the vagina and cervix, changes in vaginal flora and self-reported
      symptoms at day 14, month 1 and then monthly for up to 1 year. Acceptability was
      assessed through reported use of the gel, return of used and unused applicators,
      and quarterly interviews. RESULTS: One hundred sixty-five women were randomized:
      83 to Carraguard and 82 to the placebo (methylcellulose gel) group. Study gel use
      was similarly high in both groups throughout the trial with an average of four
      applicators per week. Carraguard use was not associated with abnormal genital
      clinical findings, abnormal vaginal flora, Pap smear abnormalities or other
      abnormal clinical signs or symptoms. Adverse events were mostly mild, not
      attributed to gel use, and similarly distributed between groups. Participants in
      both groups reported high acceptability. CONCLUSIONS: Carraguard can safely be
      used an average of four times per week with or without sex and is acceptable to
      Thai women. A Phase III efficacy trial of Carraguard is warranted and is
      currently ongoing in South Africa.

PMID- 16980908
TI  - Rapid HIV antibody testing in the New York State Anonymous HIV Counseling and
      Testing Program: experience from the field.
AB  - OBJECTIVES: To assess rapid and conventional HIV test use, client satisfaction,
      and counselors' comfort. METHODS: At 61 HIV test sites in New York State, we
      compared HIV test use during the first 6 months of rapid testing in 2003 with the
      same time period in 2002. We administered surveys to clients at each site during
      the first 30 days of rapid testing and to counselors before and after training
      and after 12 weeks of using rapid tests in the field. RESULTS: Almost all (1249
      [96.5%] of 1294) clients surveyed selected rapid over conventional HIV testing.
      During the evaluation period, 6187 HIV tests were reported, 1667 (36.9%) more
      than during the same period in 2002. All 5771 (100%) of 5771 clients received
      their rapid HIV test results compared with 333 (85.8%) of 388 clients (P <
      0.0001) who had elected conventional testing. After performing rapid testing for
      12 weeks, 32 (80%) of 40 trained counselors reported feeling "very comfortable"
      delivering reactive rapid test results compared with 14 (35%) of 40 trained
      counselors (P < 0.001) before training. CONCLUSIONS: Rapid testing presents a key
      opportunity to increase the number of people undergoing HIV testing and the
      proportion receiving their test results.

PMID- 16980909
TI  - Higher HIV-1 incidence and genetic complexity along main roads in Rakai District,
      Uganda.
AB  - OBJECTIVE: To determine the association between the incidence of HIV-1 infection
      and the genetic complexity of HIV-1 strains in 2 geographic strata within Rakai
      District, Uganda. METHODS: Study volunteers with recent HIV-1 infections during
      the period 1997 through 2003 were recruited from 10 communities that were
      geographically stratified as a main road trading center (n = 5) or a secondary
      road trading village (n = 5). Cryopreserved plasma was available from 384
      volunteers and was the source of viral RNA for genotyping by the multiregion
      hybridization assay. Hazard ratios (HRs) for a single HIV subtype, a recombinant
      form, or dual infection for gender and geographic strata were obtained using Cox
      proportional hazards analysis. RESULTS: The HIV-1 incidence rate during the
      period 1999 through 2002 was 1.3 per 100 person-years (PYs) in the trading
      centers and 1.1 per 100 PYs in the trading villages. The HR for infection with an
      HIV-1 recombinant strain in trading centers relative to trading villages was 2.3
      (95% confidence interval [CI]: 1.0 to 6.7). Among those who changed residence
      between village strata, the HR for a recombinant HIV-1 infection was 8.1 (95% CI:
      0.4 to 47.7). CONCLUSIONS: HIV-1 incidence and genetic complexity are associated
      with geographic strata and population mobility in Rakai District and are
      important variables to be considered in planning and recruitment for vaccine
      trials.

PMID- 16980910
TI  - Longitudinal anthropometric changes in HIV-infected and HIV-uninfected men.
AB  - BACKGROUND: Although morphologic abnormalities are common among HIV-infected
      persons receiving highly active antiretroviral therapy (HAART), longitudinal
      comparative body shape changes among HAART-treated HIV-infected men versus HIV
      seronegative men of similar age remain unclear. METHODS: Since September 1999,
      men enrolled in the Multicenter AIDS Cohort Study underwent body mass index (BMI)
      and circumference measurements of the waist, hip, thigh, and arm at each
      semiannual visit. Changes in these measurements that occurred between 1999 and
      2003 among HIV-infected men were compared with measurements of HIV-seronegative
      men using linear mixed effects regression models. The HIV-infected men were
      further stratified by treatment group (no antiretroviral therapy [ART],
      monotherapy or combination [mono/combo] ART, or HAART). Analyses were adjusted
      for age, nadir CD4 cell count, and BMI (for circumference measurements). RESULTS:
      Over the 4-year observation period, mean BMI increased significantly among the
      392 HIV-seronegative men (0.12 kg/m/y; P < 0.001) but did not change in the 3 HIV
      infected groups (combined n = 661). Mean waist and hip circumferences increased
      significantly in all groups. Hip circumferences increased more slowly in the HIV
      positive HAART-treated group (n = 488) than in the HIV-seronegative group (0.18
      vs. 0.49 cm/y; P < 0.001), however, yielding a more rapid increase in the
      waist/hip ratio in the HIV-positive, HAART-treated group over time (0.005 per
      year; P < 0.001). CONCLUSIONS: The increased rate of change in waist/hip ratio in
      HIV-infected men receiving HAART compared with HIV-seronegative men is
      attributable to slower increases in hip circumference rather than an increased
      rate of change in waist circumference. These findings underscore the importance
      of body fat composition changes in the peripheral compartment relative to the
      central compartment among HIV-infected men receiving HAART.

PMID- 16980911
TI  - HIV incidence trends among white and african-american active duty United States
      Army personnel (1986-2003).
AB  - OBJECTIVE: To analyze HIV incidence rate (IR) trends among white and African
      American active duty US Army personnel between 1986 and 2003. METHODS: Joinpoint
      regression was applied to identify time periods when significant changes in HIV
      IRs occurred, along with the corresponding annual percentage changes (APCs).
      RESULTS: African-Americans had a higher IR than white personnel (0.34/1,000 vs.
      0.07/1,000; P < 0.001). Among white personnel, 2 significant time periods of
      changing HIV IRs were found: between 1986 and 1989 (APC = -31.1; P = 0.006) and
      between 1989 and 2003 (APC = -5.7; P = 0.003). Among African-Americans, a
      significant decline in HIV IRs was observed only between 1986 and 1991 (APC = 
      19.4; P < 0.001). This study revealed that the HIV IRs seem to have increased in
      2 African-American groups: unmarried personnel and health care professionals.
      CONCLUSION: This cohort study (1,280 incident HIV infections among 1.5 million
      persons with 8.4 million person-years of follow-up) provides invaluable
      information on HIV trends in the United States Army. Despite an overall decline
      in HIV IRs, certain subpopulation among African-American personnel were observed
      to have increasing HIV IRs. Future research is needed to identify the current
      behavioral risk factors associated with HIV infection among US Army personnel.

PMID- 16980912
TI  - HIV incidence among injection drug users in Baltimore, Maryland (1988-2004).
AB  - BACKGROUND: We examined recent trends (1999-2004) in HIV incidence among a cohort
      of injection drug users (IDUs) followed since 1988 in Baltimore, Maryland.
      METHODS: One thousand eighty-three HIV-seronegative individuals with a history of
      injection drug use were recruited between 1988 and 1998 and returned for >or=1
      semiannual follow-up visit, where they underwent HIV antibody testing and
      interviews eliciting risk behaviors. Person-time methods were used to calculate
      HIV incidence rates per 100 person-years (PYs). RESULTS: Over 14,770 PYs, 304
      individuals seroconverted to HIV (2.06 per 100 PYs). Annual incidence declined
      from 4.57 in 1988 to 0.53 per 100 PYs in 2004. Similarly, among individuals
      actively injecting drugs, incidence steadily declined from 5.43 in 1988 to 0 in
      2004, with the exception of 2003, when an incidence of 2.59 per 100 PYs was
      observed. Reported sexual risk behaviors and drug injection declined from 1988
      through 2004, but among those actively injecting, reported needle sharing
      declined from 1988 through 1998 and then increased from 30% in 1998 to nearly 40%
      in 2003 through 2004. CONCLUSIONS: Long-term declines in HIV incidence among IDUs
      are consistent with other reports; however, in 2003, we observed an unexpected
      increase in seroconversion that seems to be related to needle sharing. Although
      additional follow-up is needed to identify trends, these data indicate the need
      to reinforce HIV prevention efforts and to continue surveillance of drug users'
      behaviors.

PMID- 16980913
TI  - Unprotected anal intercourse and substance use among men who have sex with men
      with recent HIV infection.
AB  - OBJECTIVES: To examine within-subjects and combined between- and within-subjects
      associations between substance use and unprotected anal intercourse (UAI) among
      men who have sex with men (MSM) with recent HIV infection. METHODS: One hundred
      ninety-four MSM who were recently infected with HIV completed a computer-assisted
      questionnaire regarding sexual behaviors and substance use with their last 3
      partners. Associations between UAI and substance use were assessed using
      conditional logistic regression (CLR) to assess associations among the 116 MSM
      reporting UAI with some but not all partners and generalized linear mixed effects
      models (GLMMs) to examine a combination of within- and between-subjects
      associations in the entire sample (N = 194). RESULTS: In multivariate CLR models
      and GLMMs, UAI was associated with the use of methamphetamine (odds ratio [OR] =
      4.9 and OR = 3.5, respectively), marijuana (OR = 4.0 and OR = 2.2, respectively)
      and erectile dysfunction medications (EDMs) when used with a main partner (OR =
      13.8 and OR = 10.1, respectively). CONCLUSIONS: Results indicate that a direct
      association may exist between specific substances and UAI and provide evidence
      that the use of methamphetamine and EDMs may contribute to HIV transmission.

PMID- 16980914
TI  - Multiperson use of syringes among injection drug users in a needle exchange
      program: a gene-based molecular epidemiologic analysis.
AB  - Syringe-sharing behaviors among injection drug users (IDUs) are typically based
      on self-reports and subject to socially desirable responding. We used 3 short
      tandem repeat (STR) genetic biomarkers to detect sharing in 2,512 syringes
      exchanged by 315 IDUs in the Baltimore needle exchange program (NEP; 738 person
      visits). Demographic characteristics as well as direct and indirect needle
      sharing behaviors corresponding to the closest AIDS Link to Intravenous
      Experience (ALIVE) study visits were examined for association with multiperson
      use (MPU) of syringes. Overall, 56% of the syringes exchanged at the Baltimore
      NEP had evidence of MPU. Less MPU of syringes (48% vs. 71%; P < 0.0001) was seen
      with more rapid syringe turnaround (<3 days). IDUs always exchanging their own
      syringes ("primary" syringes) were less likely to return syringes with evidence
      of MPU (52%) than those who exchanged syringes for others ("secondary" syringes;
      64%; P = 0.0001) and those exchanging primary and secondary syringes (58%; P =
      0.004). In a multivariate analysis restricted to primary exchangers, MPU of
      syringes was associated with sharing cotton (adjusted odds ratio [AOR] = 2.06,
      95% confidence interval [CI]: 1.30 to 3.28), lending syringes (AOR = 1.70, 95%
      CI: 1.24 to 2.34), and injecting less than daily (AOR = 0.64, 95% CI: 0.43 to
      0.95). These findings support additional public health interventions such as
      expanded syringe access to prevent HIV and other blood-borne infections. Testing
      of STRs represents a promising approach to examining and accessing complex
      behavioral data, including syringe sharing.

PMID- 16980915
TI  - Preliminary study on vestibular-evoked myogenic potential induced by bone
      conducted stimuli.
AB  - OBJECTIVE: To study the relationship between vestibular-evoked myogenic potential
      evoked by air-conducted stimuli (A-VEMP) and those evoked by bone-conducted
      stimuli (B-VEMP). STUDY DESIGN: Prospective study. SETTING: University Hospital.
      PATIENTS: To determine the optimum stimulus conditions for B-VEMP, 40 ears of 20
      healthy volunteers were used. To compare results of A-VEMP and B-VEMP, 60 ears of
      30 healthy volunteers and 70 ears of 35 patients with unilateral vestibular
      disorder without conductive hearing loss were used. MAIN OUTCOME MEASURE: A-VEMP
      and B-VEMP were measured. Both examinations involved evaluation of the interaural
      ratio (IAR) of the p13-n23 peak-to-peak amplitude. To compare the relationship
      between A-VEMP and B-VEMP in healthy subjects and patients with unilateral
      vestibular disorder. RESULTS: The optimum stimulus for B-VEMP seemed to be a tone
      burst sound with 8-ms duration at 250 Hz. In all healthy subjects, both A-VEMP
      and B-VEMP could be recorded. The mean IAR of B-VEMP (0.5 +/- 21.0%) was not
      significantly different from that of A-VEMP (0.2 +/- 19.4%). In patients with
      unilateral vestibular disorder, B-VEMP could not be detected in 10 ears in which
      A-VEMP also could not be detected. The IAR of A-VEMP was strongly correlated with
      that of B-VEMP (correlation coefficient, 0.98). CONCLUSION: The results of B-VEMP
      were almost the same as those for A-VEMP, at least, for patients without
      conductive hearing loss.

PMID- 16980916
TI  - Pneumococcal meningitis threshold model: A potential tool to assess infectious
      risk of new or existing inner ear surgical interventions.
AB  - HYPOTHESIS: A minimal threshold of Streptococcus pneumoniae is required to induce
      meningitis in healthy animals for intraperitoneal (hematogenous), middle ear, and
      inner ear inoculations, and this threshold may be altered via recent inner ear
      surgery. BACKGROUND: There has been an increase in the number of reported cases
      of cochlear implant-related pneumococcal meningitis since 2002. The pathogenesis
      of pneumococcal meningitis is complex and not completely understood. The bacteria
      can reach the central nervous system (CNS) from the upper respiratory tract
      mucosa via either hematogenous route or via the inner ear. The establishment of a
      threshold model for all potential routes of infection to the CNS in animals
      without cochlear implantation is an important first step to help us understand
      the pathogenesis of the disease in animals with cochlear implantation. METHODS:
      Fifty-four otologically normal adult Hooded Wistar rats (27 receiving
      cochleostomy and 27 controls) were inoculated with different amounts of bacterial
      counts via three different routes (intraperitoneal, middle ear, and inner ear).
      Rats were monitored during 5 days for signs of meningitis. Blood, cerebrospinal
      fluid, and middle ear swabs were taken for bacterial culture, and brains and
      cochleae were examined for signs of infection. RESULTS: The threshold of
      bacterial counts required to induce meningitis is lowest in rats receiving direct
      inner ear inoculation compared with both intraperitoneal and middle ear
      inoculation. There is no change in threshold between the group of rats with
      cochleostomy and the control (Fisher's exact test, p < 0.05). CONCLUSION: A
      minimal threshold of bacteria is required to induce meningitis in healthy animals
      and is different for three different routes of infection (intraperitoneal, middle
      ear, and inner ear). Cochleostomy performed 4 weeks before the inoculation did
      not reduce the threshold of bacteria required for meningitis in all three
      infectious routes. This threshold model will also serve as a valuable tool,
      assisting clinicians to quantitatively analyze if the presence of a cochlear
      implant or other CNS prostheses alter the risk of meningitis.

PMID- 16980917
TI  - Therapeutic time window of methylprednisolone in acoustic injury.
AB  - HYPOTHESIS: This study aims to investigate the therapeutic time window of
      methylprednisolone in acoustic injury. BACKGROUND: Although glucocorticoids have
      been widely used in the treatment of acoustic injury, the therapeutic time window
      of glucocorticoids in acoustic injury has never been examined. METHODS: Mice were
      exposed to 4-kHz pure tone of 128-dB sound pressure level for 4 hours. Auditory
      brainstem response was examined before, immediately after, and 2 weeks after
      acoustic overexposure. RESULTS: Methylprednisolone significantly improved the
      auditory brainstem response threshold shifts 2 weeks after acoustic overexposure
      when it was administered before or immediately after acoustic overexposure, but
      not when administered 3 hours after acoustic overexposure. CONCLUSION: The
      present findings suggest that methylprednisolone possesses protective effects
      against acoustic injury of the cochlea with a short therapeutic time window.

PMID- 16980918
TI  - Trends in HIV postexposure prophylaxis prescription and compliance after sexual
      exposure in Amsterdam, 2000-2004.
AB  - OBJECTIVE: The objective of this study was to evaluate trends in HIV postexposure
      prophylaxis (PEP) requests after sexual exposure, compliance, and outcome of
      follow-up HIV tests. STUDY DESIGN: The authors conducted a retrospective analysis
      of all HIV PEP requests after sexual exposure between January 1, 2000, and
      December 31, 2004, in Amsterdam. RESULTS: In 5 years, there was a very modest
      increase in PEP requests, of which most (75%) came from men who have sex with men
      (MSM). Although 70% reported side effects, 85% completed their PEP course. Sexual
      assault victims less often completed their course (odds ratio [OR] = 0.1; 95%
      confidence interval [CI] = 0.05-0.4, P = 0.001). People who used HIV PEP more
      often complied with follow-up tests than people who did not use PEP (OR = 3.5;
      95% CI = 1.6-7.9, P = 0.002). One HIV seroconversion was found caused by a later
      exposure than that for which PEP was given. CONCLUSIONS: Despite a widely
      available PEP program in Amsterdam, the number of PEP requests remained low. Most
      people completed their PEP course; compliance with follow-up HIV testing was
      high.

PMID- 16980919
TI  - Effects of partner notification on reducing gonorrhea incidence rate.
AB  - OBJECTIVE: The objective of this study was to estimate the effectiveness of
      partner notification (PN) by linking measures of PN with the gonorrhea incidence
      rate in New York State exclusive of New York City. STUDY DESIGN: Gonorrhea cases
      were identified from the Communicable Disease Confidential Case Reports system.
      Case interview data were obtained from the case management database. Gonorrhea
      incidence data and interview data were aggregated from individual records and
      then linked at the county level. RESULTS: From 1992 to 2002, 100,756 gonorrhea
      cases were reported and 37% were interviewed. A total of 34,807 partners were
      elicited from 37,393 index cases: 18,291 (52.5%) partners sought medical
      evaluation, 10,159 (29.2%) received preventive treatment, and 7,474 (21.5%) were
      infected and treated. The gonorrhea incidence rate was inversely correlated with
      the percent of partners given preventive treatment and positively related to the
      percent of infected partners. CONCLUSIONS: Our study adds new evidence that PN is
      an effective mechanism to detect new cases and interrupt disease transmission
      within communities.

PMID- 16980921
TI  - Cigarette smoking and thyroid eye disease: a systematic review.
AB  - PURPOSE: To evaluate the epidemiological evidence for a causal association
      between tobacco smoking and thyroid eye disease (TED). METHODS: Systematic
      review, including quality assessment, of published epidemiological studies and
      evaluation of the evidence using established causality criteria. RESULTS:
      Fourteen papers describing 15 studies were included. There was a positive
      association between smoking and TED in four case-control studies when compared
      with control patients with Graves' disease but no ophthalmopathy (odds ratio (OR)
      1.94-10.1) and in seven case-control studies in which control subjects did not
      have thyroid disease (OR 1.22-20.2). Two cohort studies examined the occurrence
      of new cases of TED; one study found an increased incidence of TED with smoking.
      Four cohort studies investigated progression or outcome of treatment in patients
      with established TED, three finding an association between smoking and poorer
      outcome. The quality of the studies was variable, but the association with
      smoking was strong in the most methodologically rigorous studies. Other evidence
      supporting a causal link was a consistent association across studies, a dose
      response effect, a reduced risk of TED in ex-smokers, and a temporal
      relationship. CONCLUSION: This systematic review provided strong evidence for a
      causal association between smoking and development of TED. Current-smokers were
      also more likely to experience disease progression or poorer outcome of
      treatment. Patients with Graves' disease and the general public should be
      educated about the risk of smoking and TED. These findings suggest that patients
      with Graves' disease or TED who are smokers should be given effective support to
      stop smoking.

PMID- 16980922
TI  - The spectrum of iris angiography abnormalities in pseudoexfoliation syndrome.
AB  - PURPOSE: To analyse the spectrum of angiographic features in patients
      monolaterally or bilaterally affected by pseudoexfoliation syndrome (PES), with
      and without glaucoma, and to evaluate the sensibility and specificity of these
      features in the diagnosis of glaucoma. METHODS: Sixty-eight patients affected by
      PES and 20 healthy subjects underwent iris fluorescein angiography (IFA) and iris
      indocyanine green angiography (IICGA). Angiographic features analysed were
      hypoperfusion, microneovascularizations, and anastomotic vessels. RESULTS: There
      was no statistically significant difference among unaffected, unilaterally
      affected, and bilaterally affected eyes. Patients affected by PES glaucoma showed
      a statistically significant difference with respect to the other groups for most
      of the variables. The results of qualitative variables revealed a gradual
      increase of the vascular involvement in the different groups. Peripupillary
      tufts, stromal tufts, and radial arterioles showed the best sensibility and
      specificity values on IFA, whereas radial arterioles and plexuses showed the
      highest sensibility and specificity values on IICGA. Considering all the
      parameters, the results were not associated with large effects on the post-test
      probability of disease. The values of likelihood ratio indicated that none of the
      examined variables was sufficiently able to discriminate patients affected by PSE
      glaucoma from the overall group. CONCLUSIONS: Patients clinically affected only
      monolaterally by PES show microvascular changes, which are similar in both eyes.
      Glaucoma PES represents a more advanced stage of the disease, with more
      pronounced alterations, even though no typical microvascular pattern can be
      identified by iris angiography.

PMID- 16980923
TI  - Nd:YAG laser subretinal membranotomy in young patients with long-term retinal
      detachment.

PMID- 16980924
TI  - Correlation between peripapillary atrophy and corticosteroid therapy in patients
      with Vogt-Koyanagi-Harada disease.
AB  - AIMS: To determine the correlation between systemic corticosteroid therapy and
      the occurrence and size of peripapillary atrophy (PPA) in patients with Vogt
      Koyanagi-Harada (VKH) disease. METHODS: All patients with VKH disease were
      retrospectively reviewed for their corticosteroid regimen. The extent of the PPA,
      if present, was measured using digitized imaging software, by two masked
      observers. Eyes with myopia greater than 6 dioptres or glaucoma were excluded.
      The patients were classified into three groups: early high (EH), late high (LH),
      and low dose (LD), according to the dose and timing of corticosteroids received
      during the acute phase of the disease. RESULTS: There were 40 eyes in the EH
      group, 25 eyes in the LH group, and 23 eyes in the LD group. Multivariate
      analysis showed that corticosteroid therapy was the main determinant of PPA
      occurrence. All the eyes in the LD group had PPA and eyes in the LH groups were
      4.02 times (95% confidence interval 1.24-13.07) more likely to develop PPA than
      those in the EH group. The LD group also had larger PPA to disc ratios than the
      EH group. (Mean of 2.83 vs0.19, P<0.001). CONCLUSION: The development and extent
      of PPA in patients with VKH disease appear to be dependent on the dose and timing
      of systemic corticosteroids.

PMID- 16980925
TI  - An observational study of laterality errors in a sample of clinical records.
AB  - BACKGROUND: Confusing left with right eyes can have a potentially serious adverse
      outcome. The most extreme occurrence is wrong site surgery but even potentially
      less serious errors can undermine patient confidence in their medical care. This
      study was designed to look into how often this could be detected in clinical
      notes. METHODS: An observational study conducted in an ophthalmic hospital.
      Hundred patients were randomly selected and their clinical notes retrieved. Notes
      were analysed for the number of left/right transpositions, which part of the
      notes they were found and whether they were corrected. RESULTS: Forty-four
      transposition errors were found in 32 sets on notes. The commonest error was
      drawing the eye on the wrong side of the page. The commonest place where errors
      were found was in the written outpatient notes. Nineteen of the errors had
      evidence of later correction. Three consent forms had the incorrect eye denoted
      and one patient was listed for surgery on the wrong side although this error was
      corrected before the operation. CONCLUSION: As far as we are aware, this study is
      the first to look at how often, in standard clinical notes, left/right
      transposition occurs. Although a direct link cannot made between their occurrence
      and later wrong side surgery, intuitively it would be reasonable to think it
      could increase the likelihood if other defences were to fail. We make a number of
      recommendations that might reduce this confusion and therefore more serious
      consequences.

PMID- 16980927
TI  - Toric posterior chamber (in-the-bag) intraocular lens implantation to correct
      postpenetrating keratoplasty astigmatism.

PMID- 16980926
TI  - Prevalence of horizontal deviation pattern changes with measurements in extreme
      gazes.
AB  - PURPOSE: To analyse the difference between measurement of A and V pattern
      strabismus at 25 degrees and extreme gaze position in esotropia (ET) and
      exotropia (XT). METHODS: This prospective cross-section study included 27
      patients with basic horizontal strabismus associated to any deviation pattern.
      Mean age was 11.88+/-9.17 (6-44) years. Exclusion criteria were amblyopia,
      intermittent XT, noncollaboration with the exam, previous strabismus surgery,
      craniofacial, or spinal abnormalities. The deviations were measured with prism
      cover test at 6 m. Measurements were carried out in primary position, upgaze
      (neck flexion of 25 degrees and maximum flexion) and downgaze (neck extension of
      25 degrees and maximum extension). A goniometer with a bubble level controlled
      the neck position. RESULTS: The most significant changes were in downgaze. The
      pattern size increased 4 prism dioptres (PD) or more in 56.25% of the V- and in
      87.5% of the A-patterns. The mean increase was 8.00+/-6.04 PD (0-17 PD) for the A
      pattern ET, 4.80+/-3.70 PD (0-10 PD) for the V-pattern XT, and 6.50+/-5.58 PD (0
      15 PD) for the V-pattern XT. The only case of A-pattern XT increased 8 PD.
      CONCLUSION: Our results suggest that measurements in extreme up and downgazes may
      uncover increased deviations in a significant proportion of cases. Further
      studies remain necessary to determine the relevance of these findings for
      strabismus correction.

PMID- 16980928
TI  - Screening for suspicious macular lesions using a telemedicine link.

PMID- 16980929
TI  - AMD: Should we screen?

PMID- 16980930
TI  - Successful retrieval of internal limiting membrane specimens.

PMID- 16980931
TI  - Intravitreal steroids may facilitate treatment of Eales' disease (idiopathic
      retinal vasculitis): an interventional case series.
AB  - PURPOSE: Eales' disease is an idiopathic peripheral perivasculitis leading to
      proliferative vascular retinopathy, recurrent vitreous haemorrhages, and
      tractional retinal detachment. It is an elusive cause of blindness in young,
      otherwise healthy individuals. We studied the effects of intravitreal
      triamcinolone acetonide (IVTA) in patients of Eales' disease, which may
      eventually reduce the side effects and cost of management, with results
      equivalent to or better than oral steroids. METHODS: Ethics approval and prior
      patient consent were obtained. Fluorescein fundus angiograms (FFAs) of 12 eyes of
      12 Eales' disease patients were taken before enrolment. These patients received
      0.1 ml of 40 mg/ml (4 mg) intravitreal triamcinolone through pars plana under
      topical anaesthesia. Regular weekly follow-ups were initiated to ascertain
      Snellen visual acuity, intraocular pressure (IOP) with Goldman tonometer, and
      triple mirror examination. Fluorescein fundus angiography was again performed in
      the 8th week to monitor response to treatment. Decrease in areas of late
      perivascular dye extravasation on fluorescein angiography was used as marker for
      improvement. RESULTS: Ten out of a total of 12 (83.33%) eyes treated with IVTA
      showed significant reduction of late leakage from retinal vessels on fluorescein
      fundus angiography. Two out of 12 eyes (16.67%) did not show considerable
      decrease in late perivascular fluorescein dye leakage after 8 weeks of
      intravitreal triamcinolone injection. Two patients (16.67%) had a significant
      rise in IOP after IVTA. CONCLUSION: Intravitreal steroids may be advocated for
      management of idiopathic retinal vasculitis without complications of systemic
      steroids, and minimize need for more invasive procedures.

PMID- 16980932
TI  - Influence of intraocular lens material on the development of acute
      endophthalmitis after cataract surgery?
AB  - PURPOSE: To investigate the causal relationship between acute postoperative
      endophthalmitis (POE) after cataract surgery and the biomaterial properties of
      the intraocular lens (IOLs) implanted. METHODS: This retrospective cohort study
      included all patients who had undergone cataract surgery with IOL implantation at
      the Lyon Croix-Rousse University Hospital between 1st January 1994 and 31st
      December 2004. Details respecting the type of IOL implanted (material and
      manufacturer) were meticulously recorded. The number of patients presenting with
      POE within 6 weeks of cataract surgery was documented together with their medical
      characteristics. These data were then compared, and Fisher's exact test was used
      to establish the significance of any apparent associations. RESULTS: Eight of the
      5837 eyes manifested acute POE (0.14%). Seven of these were composed of
      polymethylmethacrylate (PMMA) and one of heparinized PMMA. Patients with PMMA
      IOLs carried a higher risk of developing POE than did those implanted with either
      heparinized PMMA (P=0.001), hydrophilic acrylic, or hydrophobic acrylic IOLs
      (P=0.002). CONCLUSIONS: The incidence of acute POE after cataract surgery in our
      hospital is similar to that currently reported for other institutions in
      developed countries. Our results add further evidence that IOL material and type
      are factors contributing to the risk to develop an acute POE after cataract
      surgery, and that PMMA IOLs may be associated with an increased risk of POE.

PMID- 16980933
TI  - Two cases of acute macular neuroretinopathy.
AB  - PURPOSE: To report chorioretinal vasoconstriction as a potential pathogenic
      mechanism in acute macular neuroretinopathy (AMNR). To describe a time lag
      between the onset of functional deficits and that of fundoscopically visible
      lesions and illustrate the superior value of infrared (IR) compared to red-free
      or white light imaging in AMNR. METHODS: Two young female patients (30 and 19
      years old) with AMNR are described. Both underwent detailed clinical examination
      with additional imaging using IR, blue, and red-free light. Functional evaluation
      with pattern and multifocal electroretinography, Goldmann manual, and automated
      Humphrey visual fields (VFs) was also performed. RESULTS: The first patient was
      diagnosed with AMNR after a caesarian section during and after which she received
      treatment with vasoconstrictive drugs. She was followed up for 28 months, after
      which time she still suffered from bilateral U-shaped paracentral scotomata
      associated with macular lesions. The second patient complained of central
      scotomata prior to the onset of any visible fundoscopic lesions, following a bout
      of flu. VFs confirmed a central scotoma and pattern electroretinography was
      consistent with loss of macular function. Bilateral petaloid lesions became
      visible after 3 days when function began to improve. In both patients IR imaging
      was superior to standard red-free and white light in identifying macular lesions.
      CONCLUSIONS: Vasoconstriction in the chorioretina may be pathogenic in AMNR.
      Functional complaints precede fundus lesions in AMNR. And, IR light is superior
      to red-free or white light imaging in detecting typical fundus lesions in AMNR
      both early and late in the course of the disease.

PMID- 16980934
TI  - Sterile corneal ulcer with ring infiltrate and hypopyon after recurrent erosions.

PMID- 16980935
TI  - A case of sterile corneal perforation after bone marrow transplantation.

PMID- 16980936
TI  - Bacterial RNase P: a new view of an ancient enzyme.
AB  - Ribonuclease P (RNase P) is a ubiquitous endonuclease that catalyses the
      maturation of the 5' end of transfer RNA (tRNA). Although it carries out a
      biochemically simple reaction, RNase P is a complex ribonucleoprotein particle
      composed of a single large RNA and at least one protein component. In bacteria
      and some archaea, the RNA component of RNase P can catalyse tRNA maturation in
      vitro in the absence of proteins. The discovery of the catalytic activity of the
      bacterial RNase P RNA triggered numerous mechanistic and biochemical studies of
      the reactions catalysed by the RNA alone and by the holoenzyme and, in recent
      years, structures of individual components of the RNase P holoenzyme have been
      determined. The goal of the present review is to summarize what is known about
      the bacterial RNase P, and to bring together the recent structural results with
      extensive earlier biochemical and phylogenetic findings.

PMID- 16980937
TI  - Microorganisms pumping iron: anaerobic microbial iron oxidation and reduction.
AB  - Iron (Fe) has long been a recognized physiological requirement for life, yet for
      many microorganisms that persist in water, soils and sediments, its role extends
      well beyond that of a nutritional necessity. Fe(II) can function as an electron
      source for iron-oxidizing microorganisms under both oxic and anoxic conditions
      and Fe(III) can function as a terminal electron acceptor under anoxic conditions
      for iron-reducing microorganisms. Given that iron is the fourth most abundant
      element in the Earth's crust, iron redox reactions have the potential to support
      substantial microbial populations in soil and sedimentary environments. As such,
      biological iron apportionment has been described as one of the most ancient forms
      of microbial metabolism on Earth, and as a conceivable extraterrestrial
      metabolism on other iron-mineral-rich planets such as Mars. Furthermore, the
      metabolic versatility of the microorganisms involved in these reactions has
      resulted in the development of biotechnological applications to remediate
      contaminated environments and harvest energy.

PMID- 16980938
TI  - Pathogenesis of prion diseases: current status and future outlook.
AB  - The prion, a conformational variant of a host protein, is the infectious particle
      responsible for transmissible spongiform encephalopathy (TSE), a fatal
      neurodegenerative disease of humans and animals. The principal target of prion
      pathology is the brain, yet most TSEs also display prion replication at extra
      cerebral locations, including secondary lymphoid organs and sites of chronic
      inflammation. Despite significant progress in our understanding of this
      infectious agent, many fundamental questions relating to the nature of the prion,
      including the mechanism of replication and the molecular events underlying brain
      damage, remain unanswered. Here we focus on the unresolved issues pertaining to
      prion pathogenesis, particularly on the role played by the immune system.

PMID- 16980939
TI  - Bioinformatics-assisted anti-HIV therapy.
AB  - Highly active antiretroviral therapy (HAART), in which three or more drugs are
      given in combination, has substantially improved the clinical management of HIV-1
      infection. Still, the emergence of drug-resistant variants eventually leads to
      therapy failure in most patients. In such a scenario, the high diversity of
      resistance-associated mutational patterns complicates the choice of an optimal
      follow-up regimen. To support physicians in this task, a range of bioinformatics
      tools for predicting drug resistance or response to combination therapy from the
      viral genotype have been developed. With several free and commercial software
      services available, computational advice is rapidly gaining acceptance as an
      important element of rational decision-making in the treatment of HIV infection.

PMID- 16980940
TI  - Intraductal carcinoma of the prostate on needle biopsy: Histologic features and
      clinical significance.
AB  - Intraductal carcinoma of the prostate (IDC-P) has been described in radical
      prostatectomies. However, there is limited information as to its histologic
      features and clinical significance when seen on prostate biopsy. A total of 27
      cases of prostate biopsies with only IDC-P (ie no infiltrating cancer anywhere on
      the biopsy) were studied from the consult files of one of the authors. IDC-P was
      defined as malignant epithelial cells filling large acini and prostatic ducts,
      with preservation of basal cells forming either: (1) solid or dense cribriform
      patterns or; (2) loose cribriform or micropapillary patterns with either marked
      nuclear atypia (nuclear size 6 x normal or larger) or comedonecrosis. The numbers
      of cores involved by IDC-P in the biopsies ranged from 1 to 7, with >1 core
      involved in 17 cases. The architectural patterns of IDC-P were solid (12), dense
      cribriform (19), loose cribriform (17), and micropapillary (5). More than one
      pattern was present in 24 of 27 cases. The cytological features frequently
      observed in IDC-P were marked pleomorphism (18), non-focal comedonecrosis (22),
      and mitoses (20). Basal cells were observed on regular hematoxylin and eosin
      stained slides in 14 cases; in all the cases, basal cells were confirmed by
      immunohistochemical stains for high molecular weight cytokeratin (n=25) and/or
      p63 (n = 4). After the diagnosis of IDC-P on prostate biopsies, patients were
      treated by radical prostatectomy (6), radiation (7), hormone (5), combined
      radiation and hormone (1), or watchful waiting (2). The follow-up information was
      not available for six patients. The follow-up times ranged up to 4 years with an
      average of 2.1 years. In all six radical prostatectomy specimens, high-grade
      infiltrating carcinoma with Gleason score 8 or 9 was present with five cases also
      revealing prominent IDC-P. Non-focal extraprostatic extension of carcinoma was
      observed in five of the six prostatectomy cases with two cases also demonstrating
      vascular invasion. Three of 16 patients who did not receive radical prostatectomy
      developed bone metastases. Our study indicates that IDC-P on prostate biopsies is
      frequently associated with high-grade cancer and poor prognostic parameters at
      radical prostatectomy as well as potentially advanced disease following other
      therapies. These findings support prior studies that IDC-P represents an advanced
      stage of tumor progression with intraductal spread of tumor. Consideration should
      be given to treat patients with IDC-P on biopsy aggressively even in the absence
      of documented infiltrating cancer.

PMID- 16980941
TI  - Unfavorable pathological characteristics in familial colorectal cancer with low
      level microsatellite instability.
AB  - A high degree of microsatellite instability (MSI) in colorectal cancer (CRC) is a
      hallmark of hereditary non-polyposis colorectal cancer (HNPCC), caused by
      germline defects in the mismatch repair (MMR) genes. A low degree of instability
      (less than 30% of the microsatellites) is seen in a subset of tumors. To clarify
      the significance of this low degree of MSI phenotype, we studied the differences
      between patients with colorectal tumors with high-level, low-level and no MSI.
      Colorectal tumors with no (n = 68) and low-level (n = 18) MSI of patients
      clinically suspected of HNPCC were compared to colorectal tumors with high-level
      MSI (n = 12) of patients that carry a pathogenic germline mutation in a MMR gene.
      Compared to tumors with no MSI, tumors with low-level MSI were classified more
      frequently as stage T3 or T4 (100% vs 68% respectively), and showed less immune
      response (P = 0.02). No significant differences in familial CRC risk were found
      by comparing pedigrees of these two groups of tumors. Compared to the group of
      tumors with high-level MSI, the group of tumors with low-level MSI had a less
      suspicious family history, a higher percentage of lymph node metastasis (56 vs
      17%), and less immune response. Thus, with respect to genetic risks, familial CRC
      can be divided into two groups: Tumors with high-level MSI and tumors with low
      level or no MSI. However, tumors with low-level MSI show unfavorable pathological
      characteristics compared to tumors with no and tumors with high-level MSI. These
      differences suggest a distinct underlying biology of CRC with low-level MSI.

PMID- 16980942
TI  - Higher frequency of chromosomal aberrations in ovarian endometriosis compared to
      extragonadal endometriosis: A possible link to endometrioid adenocarcinoma.
AB  - Endometriosis may progress to invasive endometrioid adenocarcinoma, particularly
      in the ovary. Up to now, little is known of the molecular mechanisms possibly
      involved in the malignant transformation of endometriosis. Therefore, in this
      study, extragonadal endometriosis (n = 10), ovarian endometriosis without
      malignancy (n = 10), ovarian endometriosis with direct transition into
      endometrioid adenocarcinoma (n = 8), and normal endometrium (n = 12) were
      investigated for numerical chromosomal aberrations by fluorescence in situ
      hybridization using centromere enumeration probes. The proportions of cells with
      aneusomies were semiquantitatively assessed. Trisomies 1 and 7, and monosomies 9
      and 17 were found in endometriosis, ovarian endometrioid adenocarcinoma, and
      normal endometrium. The proportions of aneusomic cells were significantly higher
      in ovarian endometrioid carcinoma compared with ovarian endometriosis (P <
      0.001), and in ovarian endometriosis compared with extragonadal endometriosis and
      normal endometrium (P < 0.001). The data provide new evidence of a common lineage
      of endometriosis and ovarian endometrioid carcinoma. The higher frequency of
      chromosomal aberrations in endometrioid carcinoma than in endometriosis may
      reflect an expansion of aberrant cell clones already present in endometriosis
      during the progression to cancer. The higher frequency of chromosomal aberrations
      in ovarian endometriosis than in extragonadal endometriosis suggests a role of
      the ovarian stromal milieu in the induction of genetic changes, which may
      eventually lead to invasive cancer.

PMID- 16980943
TI  - Immunohistochemical expression of CDX2 in primary ovarian mucinous tumors and
      metastatic mucinous carcinomas involving the ovary: comparison with CK20 and
      correlation with coordinate expression of CK7.
AB  - Recent studies have demonstrated conflicting results regarding the value of CDX2
      for distinguishing primary ovarian mucinous tumors from metastatic mucinous
      carcinomas in the ovary. Utility of coordinate expression of cytokeratins 7 and
      20 is restricted to distinction of ovarian mucinous tumors from lower
      gastrointestinal tract metastases and data comparing coordinate expression of all
      three markers is limited. Immunohistochemical studies were performed to compare
      expression of CDX2 and cytokeratin 20, both markers of intestinal
      differentiation, in conjunction with coordinate expression of cytokeratin 7, in
      90 mucinous tumors involving the ovary: 42 primary ovarian mucinous tumors (31
      atypical proliferative (borderline) mucinous tumors (gastrointestinal type), 11
      mucinous carcinomas) and 48 metastatic mucinous carcinomas of upper
      (pancreaticobiliary tract: 14; stomach: five) and lower (colon and rectum: 25;
      appendix: four) gastrointestinal tract origin. Primary ovarian tumors expressed
      CDX2 (40%) less frequently than cytokeratin 20 (83%) (P<0.0001). CDX2 expression
      in primary ovarian tumors (40%) was lower than CDX2 expression in metastatic
      carcinomas of both upper (74%; P=0.016) and lower gastrointestinal tract origin
      (90%; P<0.0001). Cytokeratin 20 expression was similar in primary ovarian tumors
      (83%) and metastases of upper (89%; P=0.071) and lower gastrointestinal tract
      origin (93%; P=0.29). Thus, as a single marker CDX2 offers some advantage over
      cytokeratin 20 because it is less frequently positive in primary ovarian tumors.
      In the almost universally cytokeratin 7-positive primary ovarian tumors and
      metastases of upper gastrointestinal tract origin, CDX2 coordinate expression was
      less common in primary ovarian tumors (36%) than in metastases of upper
      gastrointestinal tract origin (63%) (P=0.022) whereas cytokeratin 20 coordinate
      expression was identical in both tumor types (79%). In the almost universally
      cytokeratin 7-negative metastases of lower gastrointestinal tract origin,
      coordinate expression of CDX2 (83%) and cytokeratin 20 (86%) were equivalent
      (P=1.00). CDX2 was comparable to cytokeratin 20 in distinguishing metastases of
      lower gastrointestinal tract origin (usually cytokeratin 7-negative and
      CDX2/cytokeratin 20 positive) from primary ovarian tumors and metastases of upper
      gastrointestinal tract origin (usually cytokeratin 7-positive and
      CDX2/cytokeratin 20 variable). CDX2 provided some advantage over cytokeratin 20
      for distinguishing primary ovarian mucinous tumors from metastases of upper but
      not lower gastrointestinal tract origin; however, the advantage in the former was
      limited due to the occurrence of shared coordinate expression profiles in both
      tumor types. Cytokeratin 7 provides the predominant discriminatory value among
      these markers yet is limited to distinction of primary ovarian tumors from
      metastases of lower gastrointestinal tract origin.

PMID- 16980944
TI  - Immunohistochemistry using a Mycobacterium tuberculosis complex specific antibody
      for improved diagnosis of tuberculous lymphadenitis.
AB  - The clinical and histological criteria used to diagnose lymphadenitis caused by
      Mycobacterium tuberculosis complex organisms have poor specificity. Acid-fast
      staining and culture has low sensitivity and specificity. We report a novel
      method for diagnosis of tuberculosis that uses immunohistochemistry to detect the
      secreted mycobacterial antigen MPT64 on formalin-fixed tissue biopsies. This
      antigen has not been detected in non-tuberculous mycobacteria. Polymerase chain
      reaction (PCR) for amplification of IS6110 from DNA obtained from the biopsies
      was used as a gold standard. Fifty-five cases of granulomatous lymphadenitis with
      histologically suspected tuberculosis obtained from Norway and Tanzania were
      evaluated. Four known tuberculosis cases were used as positive controls, and 16
      biopsies (12 foreign body granulomas and four other non-granulomatous cases) as
      negative controls. With immunohistochemistry, 64% (35/55) and with PCR, 60%
      (33/55) of granulomatous lymphadenitis cases were positive. Using PCR as the gold
      standard, the classical tuberculosis histology had sensitivity, specificity,
      positive and negative predictive values of 92, 37, 60, and 81%, respectively, and
      immunohistochemistry had sensitivity, specificity, positive and negative
      predictive values of 90, 83, 86, and 88%, respectively. The observed agreement
      between PCR and immunohistochemistry was 87% (kappa = 0.73). Immunohistochemistry
      with anti-MPT64 antiserum is a rapid, sensitive, and specific method for
      establishing an etiological diagnosis of tuberculosis in histologic specimens.
      Immunohistochemistry has the advantages over PCR of being robust and cheap, and
      it can easily be used in a routine laboratory.

PMID- 16980945
TI  - Steroid receptor coactivator AIB1 in endometrial carcinoma, hyperplasia and
      normal endometrium: Correlation with clinicopathologic parameters and biomarkers.
AB  - Members of the p160 steroid receptor cofactor family, including AIB1 (Amplified
      in Breast Cancer 1) (also known as SRC-3/RAC3/ACTR/pCIP/TRAM-1), are of interest
      in endometrial carcinoma as they affect the function of estrogen (ER) and
      progesterone receptors (PR). Since it is feasible that alterations in the
      expression levels of coregulators can either augment ER activity or reduce the
      ability of PR to oppose ER action in endometrial cancers, our primary aim was to
      analyze expression of the AIB1 protein in endometrial carcinoma, carcinoma
      associated complex atypical hyperplasia, and carcinoma-associated normal
      endometrium using immunohistochemistry and tissue microarrays. Expression of AIB1
      was compared with other biomarkers and clinicopathologic parameters. We also
      tested AIB1 expression in non-carcinoma associated hyperplastic, normal secretory
      and proliferative endometrium to determine baseline AIB1 levels. In endometrial
      carcinoma, there is a higher expression of AIB1 compared to carcinoma-associated
      complex atypical hyperplasia (0.007) or carcinoma-associated normal endometrium
      (<0.001). AIB1 expression correlates with older age (P = 0.003), peri- or
      postmenopausal status (P = 0.002) and a higher grade of carcinomas (P = 0.04).
      There were no differences in the expression of additional steroid hormone
      receptor co-activators (SRC-1 and p300/CBP) and the co-repressor SMRT between
      histologic categories. AIB1 expression correlated with ER (r = 0.30, P = 0.006).
      The strongest correlation was between ER and PR-B isoform nuclear expression (r =
      0.52, P < 0.0001). AIB1 levels were higher in non-carcinoma associated normal and
      hyperplastic endometrium compared to carcinoma-associated complex atypical
      hyperplasia and carcinoma-associated normal endometrium, and were the highest in
      normal secretory endometrium. In conclusion, high AIB1 expression in endometrial
      carcinoma is associated with parameters of poor prognosis. We propose that when
      AIB1 is overexpressed in endometrial carcinoma, ER action is augmented, leading
      to endometrial hyperplasia and progression to malignancy. Future studies
      correlating expression with response to hormonal therapy may be beneficial.

PMID- 16980946
TI  - Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of
      dermatofibrosarcoma protuberans.
AB  - Dermatofibrosarcoma protuberans is a superficial low-grade sarcoma that rarely
      evolves into a high-grade fibrosarcoma. Dermatofibrosarcoma protuberans is
      genetically characterized by the unbalanced chromosomal t(17;22)(q21;q13),
      usually in the form of a supernumerary ring chromosome. The product of this
      chromosomal translocation is the chimeric gene COL1A1-PDGFB (collagen type I
      alpha I-platelet-derived growth factor beta), which is amplified at low levels in
      the ring chromosome. The aims of this study were to evaluate (1) whether genomic
      gains of this fusion gene occur during the clonal evolution of
      dermatofibrosarcoma protuberans into fibrosarcomatous dermatofibrosarcoma
      protuberans and (2) whether there is a difference between the number of genomic
      copies of COL1A1-PDGFB between classic dermatofibrosarcoma protuberans and
      dermatofibrosarcoma protuberans areas associated with fibrosarcomatous
      dermatofibrosarcoma protuberans. Eleven cases of fibrosarcomatous
      dermatofibrosarcoma protuberans with both dermatofibrosarcoma protuberans and
      fibrosarcomatous areas and 10 cases of classic dermatofibrosarcoma protuberans
      were studied. Genomic copies of COL1A1-PDGFB were evaluated by fluorescence in
      situ hybridization using a custom designed probe for the PDGFB locus on 4 mum
      thick paraffin-embedded tissue sections. Genomic gains of the COL1A1-PDGFB gene
      were observed in six (of 10) fibrosarcomatous dermatofibrosarcoma protuberans in
      the fibrosarcomatous areas when compared to the dermatofibrosarcoma protuberans
      areas of the same tumor (2-7 gene copies (median PDGFB copy gain, 2.8) versus 1-3
      gene copies (median PDGFB copy gain, 1.7), respectively, P=0.004). Four
      fibrosarcomatous dermatofibrosarcoma protuberans did not show genomic gains of
      COL1A1-PDGFB fusion gene between the two areas. Essentially no difference in the
      copy number of COL1A1-PDGFB fusion gene was observed between dermatofibrosarcoma
      protuberans areas of classic dermatofibrosarcoma protuberans and
      dermatofibrosarcoma protuberans areas of fibrosarcomatous dermatofibrosarcoma
      protuberans (median PDGFB copy gain of 1.8 versus 1.7, respectively, P=0.36).
      Genomic gains of COL1A1-PDGFB fusion gene is possibly an oncogenic mechanism that
      is identified in the clonal evolution of a subset of dermatofibrosarcoma
      protuberans that evolves into fibrosarcomatous dermatofibrosarcoma protuberans.
      Since this finding was not observed in all cases of fibrosarcomatous
      dermatofibrosarcoma protuberans, other oncogenic mechanisms may be operating in
      this form of tumor progression. Copy number of COL1A1-PDGFB fusion gene in the
      classic dermatofibrosarcoma protuberans areas does not seem to be a major
      predisposing mechanism for fibrosarcomatous transformation.

PMID- 16980947
TI  - Deviated VH4 immunoglobulin gene usage is found among thyroid mucosa-associated
      lymphoid tissue lymphomas, similar to the usage at other sites, but is not found
      in thyroid diffuse large B-cell lymphomas.
AB  - It remains unclear whether or not diffuse large B-cell lymphomas of extranodal
      sites arise from mucosa-associated lymphoid tissue (MALT) lymphomas. We studied
      the clinicopathological features of MALT lymphoma and diffuse large B-cell
      lymphoma in the thyroid gland, with special reference to VH usage of
      immunoglobulin gene rearrangement, to clarify the relationships between these two
      types of lymphomas. In addition, t(11; 18) (q21; q21) translocation was examined
      by multiplex reverse transcription-polymerase chain reaction. We examined 58
      patients with primary thyroid lymphoma: 31 (male seven and female 24) with MALT
      lymphoma and 27 (male three and female 24) with diffuse large B-cell lymphoma.
      Interestingly, the sequence of VH genes revealed that the two subtypes differed
      significantly in their use of the VH4 family (P < 0.05). Of the seven MALT
      lymphomas, three used the VH4 family and the other four used the VH3 family,
      whereas eight out of nine diffuse large B-cell lymphoma used the VH3 family, one
      used the VH1 family, and none used the VH4 family. It was also interesting that,
      in one diffuse large B-cell lymphoma patient with MALT lymphoma, the diffuse
      large B-cell lymphoma component used the VH3 family and the MALT lymphoma
      component used the VH4 family. These data imply that, in a subset of cases, these
      two subtypes do not share a common origin and that at least some diffuse large B
      cell lymphomas have a de novo origin. No t(11; 18) (q21; q21) was detected in
      thyroid lymphomas, which are different from MALT lymphoma of the stomach, lungs,
      large intestine and ocular adnexa. This strongly indicated that the presence of
      t(11; 18) (q21; q21) in MALT lymphoma is organ-specific.

PMID- 16980948
TI  - IgG4-positive plasma cell infiltration in the diagnosis of autoimmune
      pancreatitis.
AB  - Autoimmune pancreatitis typically produces an enlarged pancreas with narrowing of
      the pancreatic duct, and can mimic carcinoma. Autoimmune pancreatitis usually
      responds to corticosteroid treatment, making it important to differentiate from
      pancreatic ductal adenocarcinoma. Affected patients often have an elevated serum
      IgG4. It has been proposed that increased numbers of IgG4-positive plasma cells
      in tissue might be a marker for the condition. We investigated the role of IgG4
      staining in the diagnosis of autoimmune pancreatitis, first in resected pancreas
      specimens (29 autoimmune pancreatitis, nine chronic alcoholic pancreatitis and 25
      pancreatic cancer), then in pancreatic needle biopsies. Immunohistochemical
      stains for IgG4 were scored as none, mild, moderate or marked, according to
      published criteria. Moderate to marked numbers of IgG4-positive plasma cells were
      seen in 21/29 autoimmune pancreatitis patients, and were distributed in and
      around ducts, in interlobular fibrous tissue and in peripancreatic fat. In
      contrast, eight of nine examples of chronic alcoholic pancreatitis and 22/25
      ductal adenocarcinomas had scores of none or mild. When we subdivided autoimmune
      pancreatitis into the histologic subtypes lymphoplasmacytic sclerosing
      pancreatitis and idiopathic duct-destructive pancreatitis, 16/17
      lymphoplasmacytic sclerosing pancreatitis had moderate to marked staining,
      compared to five to 12 idiopathic duct-destructive pancreatitis. Needle biopsies
      from nine patients suspected of having autoimmune pancreatitis had increased
      numbers of IgG4 cells. We conclude that pancreatic tissue from patients with
      autoimmune pancreatitis often shows moderate or marked infiltration by IgG4
      positive plasma cells (>10/HPF). This is particularly so in the subtype we have
      designated lymphoplasmacytic sclerosing pancreatitis. We rarely see IgG4 staining
      in patients with chronic alcoholic pancreatitis and pancreatic ductal
      adenocarcinoma. IgG4-positive plasma cells are a useful marker for the tissue
      diagnosis of autoimmune pancreatitis.

PMID- 16980949
TI  - Matrix metalloproteinase type 2 expression in malignant adrenocortical tumors:
      Diagnostic and prognostic significance in a series of 50 adrenocortical
      carcinomas.
AB  - The differential diagnosis of adrenocortical carcinoma from adrenocortical
      adenoma is based on different pathological parameters, usually incorporated in
      scoring systems, which unfortunately lack a 100% sensitivity and specificity.
      Little is known on the molecular mechanisms leading to the malignant phenotype in
      adrenocortical tumors. Among other molecules, metalloproteinases were
      demonstrated to be implicated in malignant progression and metastatization of
      solid tumors, including endocrine ones. Therefore, we aimed to investigate
      metalloproteinases and their inhibitors expression in a series of 50
      adrenocortical carcinomas and 50 control adrenocortical adenomas, diagnosed
      according to the Weiss histological criteria. Immunohistochemical results were
      scored by semiquantitative analysis and compared with clinicopathological
      parameters and outcome. Metalloproteinase type 2 gave the most significant
      result, being detected in neoplastic cells in 1/50 adrenocortical adenomas (2%)
      and 37/50 adrenocortical carcinomas (74%) (P < 0.001), with a focal (score 1,
      <20% of positive cells--two-thirds of cases) or diffuse (score 2, >20% of
      positive cells--one-third of cases) pattern. In addition, diffuse (score 2)
      metalloproteinase type 2 protein expression, as compared to focal or negative
      immunostaining, correlated with shorter survival (P < 0.02) and disease-free
      interval (P = 0.05). No correlation was found comparing metalloproteinase type 2
      expression and any clinicopathological parameter. Our data indicate that
      metalloproteinase type 2 immunohistochemical localization in tumor cells is
      significantly restricted to malignant adrenocortical tumors, with high
      specificity but low sensitivity. In addition, a strong metalloproteinase type 2
      expression in adrenocortical carcinoma was for the first time recognized as an
      unfavorable prognostic factor.

PMID- 16980950
TI  - Immunoglobulin VH somatic hypermutation in mantle cell lymphoma: mutated genotype
      correlates with better clinical outcome.
AB  - Mantle cell lymphoma is an aggressive B-cell lymphoma for which the biology is
      incompletely understood. Previous studies have reported that somatic
      hypermutation of the variable region of the immunoglobulin heavy chain gene
      (V(H)), as commonly defined as <98% homology, can be detected in approximately
      one-third of mantle cell lymphoma, although the V(H) mutation status has not been
      found to significantly correlate with patient survival. In this study, we
      assessed V(H) mutation in 55 mantle cell lymphomas using a method slightly
      different from those used in the previous studies, and we came to different
      conclusions. Using DNA extracted from formalin-fixed/paraffin-embedded tumors in
      all cases, we identified monoclonal IGH bands in 54 of 55 cases with the
      FR1c/J(H) primer; a monoclonal IGH band was amplified using another IGH primer
      set, FR256/J(H), in the remaining case. Cloning was performed in all cases, and
      an average of six clones were sequenced and analyzed for each case. Intraclonal
      heterogeneity was detected in 45 (82%) cases. Further analysis was performed in
      53 cases, in which a predominant IGH species was identified. Most (32 of 53
      cases, 60%) cases were 'mutated', with <98% homology. V(H)1-69, V(H)4-59 and
      V(H)3-74 were utilized in 29 (55%) cases. Intraclonal evolution and non
      productive V(H) rearrangements were more frequent in the mutated group. Patients
      with the 'mutated' genotype had longer overall survival (P=0.017, Log rank) that
      is independent of the international prognostic index. To conclude, our data
      suggest that the V(H) mutation frequency in mantle cell lymphoma may be higher
      than previously believed. Importantly, using our methodology, we found that the
      V(H) mutation status may be a useful prognostic marker for these patients.

PMID- 16980951
TI  - Positional expression profiling indicates candidate genes in deletion hotspots of
      hepatocellular carcinoma.
AB  - Molecular characterizations of hepatocellular carcinoma have indicated frequent
      allelic losses on chromosomes 4q, 8p, 16q and 17p, where the minimal deleted
      regions have been further defined on 4q12-q23, 4q31-q35, 8p21-p22, 16q12.1-q23.1
      and 17p13. Despite these regions are now well-recognized in early liver
      carcinogenesis, few underlying candidate genes have been identified. In an effort
      to define affected genes within common deleted loci of hepatocellular carcinoma,
      we conducted transcriptional mapping by high-resolution cDNA microarray analysis.
      In 20 hepatocellular carcinoma cell lines and 20 primary tumors studied,
      consistent downregulations of novel transcripts were highlighted throughout the
      entire genome and within sites of frequent losses. The array-derived candidates
      including fibrinogen gamma peptide (FGG, at 4q31.3), vitamin D binding protein
      (at 4q13.3), fibrinogen-like 1 (FGL1, at 8p22), metallothionein 1G (MT1G, at
      16q12.2) and alpha-2-plasmin inhibitor (SERPINF2, at 17p13) were confirmed by
      quantitative reverse transcription-polymerase chain reaction, which also
      indicated a more profound downregulation of FGL1, MT1G and SERPINF2 relative to
      reported tumor-suppressor genes, such as DLC1 (8p22), E-cadherin (16q22.1) and
      TP53 (17p13.1). In primary hepatocellular carcinoma examined, a significant
      repression of MT1G by more than 100-fold was indicated in 63% of tumors compared
      to the adjacent nonmalignant liver (P = 0.0001). Significant downregulations of
      FGG, FGL1 and SERPINF2 were also suggested in 30, 23 and 33% of cases,
      respectively, compared to their nonmalignant counterparts (P < 0.016). In
      summary, transcriptional mapping by microarray indicated a number of previously
      undescribed downregulated genes in hepatocellular carcinoma, and highlighted
      potential candidates within common deleted regions.

PMID- 16980953
TI  - Tunable spin-tunnel contacts to silicon using low-work-function ferromagnets.
AB  - Magnetic tunnel junctions have become ubiquitous components appearing in magnetic
      random-access memory, read heads of magnetic disk drives and semiconductor-based
      spin devices. Inserting a tunnel barrier has been key to achieving spin injection
      from ferromagnetic (FM) metals into GaAs, but spin injection into Si has remained
      elusive. We show that Schottky barrier formation leads to a huge conductivity
      mismatch of the FM tunnel contact and Si, which cannot be solved by the well
      known method of adjusting the tunnel barrier thickness. We present a radically
      different approach for spin-tunnelling resistance control using low-work-function
      ferromagnets, inserted at the FM/tunnel barrier interface. We demonstrate that in
      this way the resistance-area (RA) product of FM/Al2O3/Si contacts can be tuned
      over eight orders of magnitude, while simultaneously maintaining a reasonable
      tunnel spin polarization. This raises prospects for Si-based spintronics and
      presents a new category of ferromagnetic materials for spin-tunnel contacts in
      low-RA-product applications.

PMID- 16980954
TI  - Shock deformation of face-centred-cubic metals on subnanosecond timescales.
AB  - Despite its fundamental importance for a broad range of applications, little is
      understood about the behaviour of metals during the initial phase of shock
      compression. Here, we present molecular dynamics (MD) simulations of shock-wave
      propagation through a metal allowing a detailed analysis of the dynamics of high
      strain-rate plasticity. Previous MD simulations have not seen the evolution of
      the strain from one- to three-dimensional compression that is observed in
      diffraction experiments. Our large-scale MD simulations of up to 352 million
      atoms resolve this important discrepancy through a detailed understanding of
      dislocation flow at high strain rates. The stress relaxes to an approximately
      hydrostatic state and the dislocation velocity drops to nearly zero. The
      dislocation velocity drop leads to a steady state with no further relaxation of
      the lattice, as revealed by simulated X-ray diffraction.

PMID- 16980956
TI  - Symbiosis insights through metagenomic analysis of a microbial consortium.
AB  - Symbioses between bacteria and eukaryotes are ubiquitous, yet our understanding
      of the interactions driving these associations is hampered by our inability to
      cultivate most host-associated microbes. Here we use a metagenomic approach to
      describe four co-occurring symbionts from the marine oligochaete Olavius
      algarvensis, a worm lacking a mouth, gut and nephridia. Shotgun sequencing and
      metabolic pathway reconstruction revealed that the symbionts are sulphur
      oxidizing and sulphate-reducing bacteria, all of which are capable of carbon
      fixation, thus providing the host with multiple sources of nutrition. Molecular
      evidence for the uptake and recycling of worm waste products by the symbionts
      suggests how the worm could eliminate its excretory system, an adaptation unique
      among annelid worms. We propose a model that describes how the versatile
      metabolism within this symbiotic consortium provides the host with an optimal
      energy supply as it shuttles between the upper oxic and lower anoxic coastal
      sediments that it inhabits.

PMID- 16980957
TI  - Sall4 modulates embryonic stem cell pluripotency and early embryonic development
      by the transcriptional regulation of Pou5f1.
AB  - Embryonic stem (ES) cells are pluripotent cells that can self-renew or
      differentiate into many cell types. A unique network of transcription factors and
      signalling molecules are essential for maintaining this capability. Here, we
      report that a spalt family member, Sall4, is required for the pluripotency of ES
      cells. Similarly to Oct4, a reduction in Sall4 levels in mouse ES cells results
      in respecification, under the appropriate culture conditions, of ES cells to the
      trophoblast lineage. Sall4 regulates transcription of Pou5f1 which encodes Oct4.
      Sall4 binds to the highly conserved regulatory region of the Pou5f1 distal
      enhancer and activates Pou5f1 expression in vivo and in vitro. Microinjection of
      Sall4 small interfering (si) RNA into mouse zygotes resulted in reduction of
      Sall4 and Oct4 mRNAs in preimplantation embryos and significant expansion of Cdx2
      expression into the inner cell mass. These results demonstrate that Sall4 is a
      transcriptional activator of Pou5f1 and has a critical role in the maintenance of
      ES cell pluripotency by modulating Oct4 expression. The data also indicates that
      Sall4 is important for early embryonic cell-fate decisions.

PMID- 16980958
TI  - Cytosolic chaperonin prevents polyglutamine toxicity with altering the
      aggregation state.
AB  - Polyglutamine (polyQ)-expansion proteins cause neurodegenerative disorders
      including Huntington's disease, Kennedy's disease and various ataxias. The
      cytotoxicity of these proteins is associated with the formation of aggregates or
      other conformationally toxic species. Here, we show that the cytosolic chaperonin
      CCT (also known as TRiC) can alter the course of aggregation and cytotoxicity of
      huntingtin (Htt)-polyQ proteins in mammalian cells. Disruption of the CCT complex
      by RNAi-mediated knockdown enhanced Htt-polyQ aggregate formation and cellular
      toxicity. Analysis of the aggregation states of the Htt-polyQ proteins by
      fluorescence correlation spectroscopy revealed that CCT depletion results in the
      appearance of soluble Htt-polyQ aggregates. Similarly, overexpression of all
      eight subunits of CCT suppressed Htt aggregation and neuronal cell death. These
      results indicate that CCT has an essential role in protecting against the
      cytotoxicity of polyQ proteins by affecting the course of aggregation.

PMID- 16980959
TI  - The chaperonin TRiC controls polyglutamine aggregation and toxicity through
      subunit-specific interactions.
AB  - Misfolding and aggregation of proteins containing expanded polyglutamine repeats
      underlie Huntington's disease and other neurodegenerative disorders. Here, we
      show that the hetero-oligomeric chaperonin TRiC (also known as CCT) physically
      interacts with polyglutamine-expanded variants of huntingtin (Htt) and
      effectively inhibits their aggregation. Depletion of TRiC enhances polyglutamine
      aggregation in yeast and mammalian cells. Conversely, overexpression of a single
      TRiC subunit, CCT1, is sufficient to remodel Htt-aggregate morphology in vivo and
      in vitro, and reduces Htt-induced toxicity in neuronal cells. Because TRiC acts
      during de novo protein biogenesis, this chaperonin may have an early role
      preventing Htt access to pathogenic conformations. Based on the specificity of
      the Htt-CCT1 interaction, the CCT1 substrate-binding domain may provide a
      versatile scaffold for therapeutic inhibitors of neurodegenerative disease.

PMID- 16980960
TI  - The Plk1 target Kizuna stabilizes mitotic centrosomes to ensure spindle
      bipolarity.
AB  - Formation of a bipolar spindle is essential for faithful chromosome segregation
      at mitosis. Because centrosomes define spindle poles, defects in centrosome
      number and structural organization can lead to a loss of bipolarity. In addition,
      microtubule-mediated pulling and pushing forces acting on centrosomes and
      chromosomes are also important for bipolar spindle formation. Polo-like kinase 1
      (Plk1) is a highly conserved Ser/Thr kinase that has essential roles in the
      formation of a bipolar spindle with focused poles. However, the mechanism by
      which Plk1 regulates spindle-pole formation is poorly understood. Here, we
      identify a novel centrosomal substrate of Plk1, Kizuna (Kiz), depletion of which
      causes fragmentation and dissociation of the pericentriolar material from
      centrioles at prometaphase, resulting in multipolar spindles. We demonstrate that
      Kiz is critical for establishing a robust mitotic centrosome architecture that
      can endure the forces that converge on the centrosomes during spindle formation,
      and suggest that Plk1 maintains the integrity of the spindle poles by
      phosphorylating Kiz.

PMID- 16980961
TI  - An oxidation-sensing mechanism is used by the global regulator MgrA in
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a human pathogen responsible for most wound and hospital
      acquired infections. The protein MgrA is both an important virulence determinant
      during infection and a regulator of antibiotic resistance in S. aureus. The
      crystal structure of the MgrA homodimer, solved at 2.86 A, indicates the presence
      of a unique cysteine residue located at the interface of the protein dimer. We
      discovered that this cysteine residue can be oxidized by various reactive oxygen
      species, such as hydrogen peroxide and organic hydroperoxide. Cysteine oxidation
      leads to dissociation of MgrA from DNA and initiation of signaling pathways that
      turn on antibiotic resistance in S. aureus. The oxidation-sensing mechanism is
      typically used by bacteria to counter challenges of reactive oxygen and nitrogen
      species. Our study reveals that in S. aureus, MgrA adopts a similar mechanism but
      uses it to globally regulate different defensive pathways.

PMID- 16980962
TI  - Kinase activity of mutant LRRK2 mediates neuronal toxicity.
AB  - Mutations in the the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal
      dominant Parkinson disease and some cases of sporadic Parkinson disease. Here we
      found that LRRK2 kinase activity was regulated by GTP via the intrinsic GTPase
      Roc domain, and alterations of LRRK2 protein that reduced kinase activity of
      mutant LRRK2 correspondingly reduced neuronal toxicity. These data elucidate the
      pathogenesis of LRRK2-linked Parkinson disease, potentially illuminate mechanisms
      of sporadic Parkinson disease and suggest therapeutic targets.

PMID- 16980963
TI  - Asymmetrical beta-actin mRNA translation in growth cones mediates attractive
      turning to netrin-1.
AB  - Local protein synthesis regulates the turning of growth cones to guidance cues,
      yet little is known about which proteins are synthesized or how they contribute
      to directional steering. Here we show that beta-actin mRNA resides in Xenopus
      laevis retinal growth cones where it binds to the RNA-binding protein Vg1RBP.
      Netrin-1 induces the movement of Vg1RBP granules into filopodia, suggesting that
      it may direct the localization and translation of mRNAs in growth cones. Indeed,
      a gradient of netrin-1 activates a translation initiation regulator, eIF-4E
      binding protein 1 (4EBP), asymmetrically and triggers a polarized increase in
      beta-actin translation on the near side of the growth cone before growth cone
      turning. Inhibition of beta-actin translation abolishes both the asymmetric rise
      in beta-actin and attractive, but not repulsive, turning. Our data suggest that
      newly synthesized beta-actin, concentrated near sites of signal reception,
      provides the directional bias for polymerizing actin in the direction of an
      attractive stimulus.

PMID- 16980964
TI  - Local caspase activity directs engulfment of dendrites during pruning.
AB  - Pruning is important for sculpting neural circuits, as it removes excessive or
      inaccurate projections. Here we show that the removal of sensory neuron dendrites
      during pruning in Drosophila melanogaster is directed by local caspase activity.
      Suppressing caspase activity prevented dendrite removal, whereas a global
      activation of caspases within a neuron caused cell death. A new genetically
      encoded caspase probe revealed that caspase activity is confined to the
      degenerating dendrites of pruning neurons.

PMID- 16980965
TI  - An essential role for beta-actin mRNA localization and translation in Ca2+
      dependent growth cone guidance.
AB  - Axon pathfinding requires directional responses of growth cones to extracellular
      cues, which have been shown to involve local synthesis of protein. The identity
      and functions of the locally produced proteins remain, however, unclear. Here we
      report that Ca(2+)-dependent bidirectional turning of Xenopus laevis growth cones
      requires localized distribution and translation of beta-actin messenger RNA. Both
      beta-actin mRNA and its zipcode-binding protein, ZBP1, are localized at the
      growth cone and become asymmetrically distributed upon local exposure to brain
      derived neurotrophic factor (BDNF). Inhibition of protein synthesis or antisense
      interference with beta-actin mRNA-ZBP1 binding abolishes both Ca(2+)-mediated
      attraction and repulsion. In addition, attraction involves a local increase in
      beta-actin, whereas repulsion is accompanied by a local decrease in beta-actin;
      thus, both produce a synthesis- and ZBP1 binding-dependent beta-actin asymmetry
      but with opposite polarities. Together with a similar asymmetry in Src activity
      during bidirectional responses, our findings indicate that Ca(2+)-dependent
      spatial regulation of beta-actin synthesis through Src contributes to the
      directional motility of growth cones during guidance.

PMID- 16980966
TI  - Functional alignment of feedback effects from visual cortex to thalamus.
AB  - Following from the classical work of Hubel and Wiesel, it has been recognized
      that the orientation and the on- and off-zones of receptive fields of layer 4
      simple cells in the visual cortex are linked to the spatial alignment and
      properties of the cells in the visual thalamus that relay the retinal input. Here
      we present evidence showing that the orientation and the on- and off-zones of
      receptive fields of layer 6 simple cells in cat visual cortex that provide
      feedback to the thalamus are similarly linked to the alignment and properties of
      the receptive fields of the thalamic cells they contact. However, the pattern of
      influence linked to on- and off-zones is phase-reversed. This has important
      functional implications.

PMID- 16980967
TI  - NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse
      formation.
AB  - Synaptic cell adhesion molecules (CAMs) regulate synapse formation through their
      trans-synaptic and heterophilic adhesion. Here we show that postsynaptic netrin-G
      ligand (NGL) CAMs associate with netrin-G CAMs in an isoform-specific manner and,
      through their cytosolic tail, with the abundant postsynaptic scaffold
      postsynaptic density-95 (PSD-95). Overexpression of NGL-2 in cultured rat neurons
      increased the number of PSD-95-positive dendritic protrusions. NGL-2 located on
      heterologous cells or beads induced functional presynaptic differentiation in
      contacting neurites. Direct aggregation of NGL-2 on the surface membrane of
      dendrites induced the clustering of excitatory postsynaptic proteins. Competitive
      inhibition by soluble NGL-2 reduced the number of excitatory synapses. NGL-2
      knockdown reduced excitatory, but not inhibitory, synapse numbers and currents.
      These results suggest that NGL regulates the formation of excitatory synapses.

PMID- 16980968
TI  - Functional and morphological recovery of dystrophic muscles in mice treated with
      deacetylase inhibitors.
AB  - Pharmacological interventions that increase myofiber size counter the functional
      decline of dystrophic muscles. We show that deacetylase inhibitors increase the
      size of myofibers in dystrophin-deficient (MDX) and alpha-sarcoglycan (alpha-SG)
      deficient mice by inducing the expression of the myostatin antagonist follistatin
      in satellite cells. Deacetylase inhibitor treatment conferred on dystrophic
      muscles resistance to contraction-coupled degeneration and alleviated both
      morphological and functional consequences of the primary genetic defect. These
      results provide a rationale for using deacetylase inhibitors in the
      pharmacological therapy of muscular dystrophies.

PMID- 16980969
TI  - Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis.
AB  - The avascularity of cardiac valves is abrogated in several valvular heart
      diseases (VHDs). This study investigated the molecular mechanisms underlying
      valvular avascularity and its correlation with VHD. Chondromodulin-I, an
      antiangiogenic factor isolated from cartilage, is abundantly expressed in cardiac
      valves. Gene targeting of chondromodulin-I resulted in enhanced Vegf-A
      expression, angiogenesis, lipid deposition and calcification in the cardiac
      valves of aged mice. Echocardiography showed aortic valve thickening,
      calcification and turbulent flow, indicative of early changes in aortic stenosis.
      Conditioned medium obtained from cultured valvular interstitial cells strongly
      inhibited tube formation and mobilization of endothelial cells and induced their
      apoptosis; these effects were partially inhibited by chondromodulin-I small
      interfering RNA. In human VHD, including cases associated with infective
      endocarditis, rheumatic heart disease and atherosclerosis, VEGF-A expression,
      neovascularization and calcification were observed in areas of chondromodulin-I
      downregulation. These findings provide evidence that chondromodulin-I has a
      pivotal role in maintaining valvular normal function by preventing angiogenesis
      that may lead to VHD.

PMID- 16980970
TI  - G-CSF induces E-selectin ligand expression on human myeloid cells.
AB  - Clinical use of G-CSF can result in vascular and inflammatory complications. To
      investigate the molecular basis of these effects, we analyzed the adherence of G
      CSF-mobilized human peripheral blood leukocytes (ML) to inflamed (TNF-alpha
      stimulated) vascular endothelium. Studies using parallel plate assays under
      physiologic flow conditions and intravital microscopy in a mouse inflammation
      model each showed that ML take part in heightened adhesive interactions with
      endothelium compared to unmobilized (native) blood leukocytes, mediated by
      markedly increased E-selectin receptor-ligand interactions. Biochemical studies
      showed that ML express the potent E-selectin ligand HCELL (ref. 8) and another,
      previously unrecognized approximately 65-kDa E-selectin ligand, and possess
      enhanced levels of transcripts encoding glycosyltransferases (ST3GalIV, FucT-IV
      and FucT-VII) conferring glycan modifications associated with E-selectin ligand
      activity. Enzymatic treatments and physiologic binding assays showed that HCELL
      and the approximately 65-kDa E-selectin ligand contribute prominently to the
      observed G-CSF-induced myeloid cell adhesion to inflamed endothelium. Treatment
      of normal human bone marrow cells with a pharmacokinetically relevant
      concentration of G-CSF in vitro resulted in increased expression of these two
      molecules, coincident with increased transcripts encoding pertinent
      glycosyltransferases and heightened E-selectin binding. These findings provide
      direct evidence for a role of G-CSF in the induction of E-selectin ligands on
      myeloid cells, thus providing mechanistic insight into the pathobiology of G-CSF
      complications.

PMID- 16980971
TI  - Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage
      specific polyubiquitin chain formation.
AB  - Lys63-linked polyubiquitin chains participate in nonproteolytic signaling
      pathways, including regulation of DNA damage tolerance and NF-kappaB activation.
      E2 enzymes bound to ubiquitin E2 variants (UEV) are vital in these pathways,
      synthesizing Lys63-linked polyubiquitin chains, but how these complexes achieve
      specificity for a particular lysine linkage has been unclear. We have determined
      the crystal structure of an Mms2-Ubc13-ubiquitin (UEV-E2-Ub) covalent
      intermediate with donor ubiquitin linked to the active site residue of Ubc13. In
      the structure, the unexpected binding of a donor ubiquitin of one Mms2-Ubc13-Ub
      complex to the acceptor-binding site of Mms2-Ubc13 in an adjacent complex allows
      us to visualize at atomic resolution the molecular determinants of acceptor
      ubiquitin binding. The structure reveals the key role of Mms2 in allowing
      selective insertion of Lys63 into the Ubc13 active site and suggests a molecular
      model for polyubiquitin chain elongation.

PMID- 16980972
TI  - Structure of a human ASF1a-HIRA complex and insights into specificity of histone
      chaperone complex assembly.
AB  - Human HIRA, ASF1a, ASF1b and CAF-1 are evolutionally conserved histone chaperones
      that form multiple functionally distinct chromatin-assembly complexes, with roles
      linked to diverse nuclear process, such as DNA replication and formation of
      heterochromatin in senescent cells. We report the crystal structure of an ASF1a
      HIRA heterodimer and a biochemical dissection of ASF1a's mutually exclusive
      interactions with HIRA and the p60 subunit of CAF-1. The HIRA B domain forms an
      antiparallel beta-hairpin that binds perpendicular to the strands of the beta
      sandwich of ASF1a, via beta-sheet, salt bridge and van der Waals contacts. The N-
      and C-terminal regions of ASF1a and ASF1b determine the different affinities of
      these two proteins for HIRA, by contacting regions outside the HIRA B domain. CAF
      1 p60 also uses B domain-like motifs for binding to ASF1a, thereby competing with
      HIRA. Together, these studies begin to define the molecular determinants of
      assembly of functionally diverse macromolecular histone chaperone complexes.

PMID- 16980973
TI  - Slow translocon gating causes cytosolic exposure of transmembrane and lumenal
      domains during membrane protein integration.
AB  - Integral membrane proteins are cotranslationally inserted into the endoplasmic
      reticulum via the protein translocation channel, or translocon, which mediates
      the transport of lumenal domains, retention of cytosolic domains and integration
      of transmembrane spans into the phospholipid bilayer. Upon translocon binding,
      transmembrane spans interact with a lateral gate, which regulates access to
      membrane phospholipids, and a lumenal gate, which controls the translocation of
      soluble domains. We analyzed the in vivo kinetics of integration of model
      membrane proteins in Saccharomyces cerevisiae using ubiquitin translocation assay
      reporters. Our findings indicate that the conformational changes in the
      translocon that permit opening of the lumenal and lateral channel gates occur
      less rapidly than elongation of the nascent polypeptide. Transmembrane spans and
      lumenal domains are therefore exposed to the cytosol during integration of a
      polytopic membrane protein, which may pose a challenge to the fidelity of
      membrane protein integration.

PMID- 16980974
TI  - Human C5aR knock-in mice facilitate the production and assessment of anti
      inflammatory monoclonal antibodies.
AB  - Complement component C5a binds C5a receptor (C5aR) and facilitates leukocyte
      chemotaxis and release of inflammatory mediators. We used neutrophils from human
      C5aR knock-in mice, in which the mouse C5aR coding region was replaced with that
      of human C5aR, to immunize wild-type mice and to generate high-affinity
      antagonist monoclonal antibodies (mAbs) to human C5aR. These mAbs blocked
      neutrophil migration to C5a in vitro and, at low doses, both prevented and
      reversed inflammatory arthritis in the murine K/BxN model. Of approximately 40
      mAbs generated to C5aR, all potent inhibitors recognized a small region of the
      second extracellular loop that seems to be critical for regulation of receptor
      activity. Human C5aR knock-in mice not only facilitated production of high
      affinity mAbs against an important human therapeutic target but were also useful
      in preclinical validation of the potency of these antagonists. This strategy
      should be applicable to other important mAb therapeutics.

PMID- 16980975
TI  - Efficient enucleation of erythroblasts differentiated in vitro from hematopoietic
      stem and progenitor cells.
AB  - Erythroblast enucleation is thought to be largely dependent on signals mediated
      by other cells, such as macrophages. In an attempt to improve the in vitro
      production of red blood cells (RBCs) from immature hematopoietic progenitor
      cells, we have developed a method to produce enucleated RBCs efficiently in the
      absence of feeder cells. Our method may represent an efficient way to produce
      transfusable RBCs on a large scale from hematopoietic progenitors.

PMID- 16980976
TI  - Delineation of a Fat tumor suppressor pathway.
AB  - Recent studies in Drosophila melanogaster of the protocadherins Dachsous and Fat
      suggest that they act as ligand and receptor, respectively, for an intercellular
      signaling pathway that influences tissue polarity, growth and gene expression,
      but the basis for signaling downstream of Fat has remained unclear. Here, we
      characterize functional relationships among D. melanogaster tumor suppressors and
      identify the kinases Discs overgrown and Warts as components of a Fat signaling
      pathway. fat, discs overgrown and warts regulate a common set of downstream genes
      in multiple tissues. Genetic experiments position the action of discs overgrown
      upstream of the Fat pathway component dachs, whereas warts acts downstream of
      dachs. Warts protein coprecipitates with Dachs, and Warts protein levels are
      influenced by fat, dachs and discs overgrown in vivo, consistent with its
      placement as a downstream component of the pathway. The tumor suppressors Merlin,
      expanded, hippo, salvador and mob as tumor suppressor also share multiple Fat
      pathway phenotypes but regulate Warts activity independently. Our results
      functionally link what had been four disparate groups of D. melanogaster tumor
      suppressors, establish a basic framework for Fat signaling from receptor to
      transcription factor and implicate Warts as an integrator of multiple growth
      control signals.

PMID- 16980977
TI  - Quantitative and predictive model of transcriptional control of the Drosophila
      melanogaster even skipped gene.
AB  - Here we present a quantitative and predictive model of the transcriptional
      readout of the proximal 1.7 kb of the control region of the Drosophila
      melanogaster gene even skipped (eve). The model is based on the positions and
      sequence of individual binding sites on the DNA and quantitative, time-resolved
      expression data at cellular resolution. These data demonstrated new expression
      features, first reported here. The model correctly predicts the expression
      patterns of mutations in trans, as well as point mutations, insertions and
      deletions in cis. It also shows that the nonclassical expression of stripe 7
      driven by this fragment is activated by the protein Caudal (Cad), and repressed
      by the proteins Tailless (Tll) and Giant (Gt).

PMID- 16980978
TI  - Secretory COPII coat component Sec23a is essential for craniofacial chondrocyte
      maturation.
AB  - An increasing number of human disorders have been linked to mutations in genes of
      the secretory pathway. The chemically induced zebrafish crusher variant results
      in malformed craniofacial skeleton, kinked pectoral fins and a short body length.
      By positional cloning, we identified a nonsense mutation converting leucine to a
      stop codon (L402X) in the sec23a gene, an integral component of the COPII
      complex, which is critical for anterograde protein trafficking between
      endoplasmic reticulum and Golgi apparatus. Zebrafish crusher mutants develop
      normally until the onset of craniofacial chondrogenesis. crusher chondrocytes
      accumulate proteins in a distended endoplasmic reticulum, resulting in severe
      reduction of cartilage extracellular matrix (ECM) deposits, including type II
      collagen. We demonstrate that the paralogous gene sec23b is also an essential
      component of the ECM secretory pathway in chondrocytes. In contrast, knockdown of
      the COPI complex does not hinder craniofacial morphogenesis. As SEC23A lesions
      cause the cranio-lenticulo-sutural dysplasia syndrome, crusher provides the first
      vertebrate model system that links the biology of endoplasmic reticulum to Golgi
      trafficking with a clinically relevant dysmorphology.

PMID- 16980979
TI  - Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to
      abnormal endoplasmic-reticulum-to-Golgi trafficking.
AB  - Cranio-lenticulo-sutural dysplasia (CLSD) is an autosomal recessive syndrome
      characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms
      and skeletal defects mapped to chromosome 14q13-q21 (ref. 1). Here we show, using
      a positional cloning approach, that an F382L amino acid substitution in SEC23A
      segregates with this syndrome. SEC23A is an essential component of the COPII
      coated vesicles that transport secretory proteins from the endoplasmic reticulum
      to the Golgi complex. Electron microscopy and immunofluorescence show that there
      is gross dilatation of the endoplasmic reticulum in fibroblasts from individuals
      affected with CLSD. These cells also exhibit cytoplasmic mislocalization of
      SEC31. Cell-free vesicle budding assays show that the F382L substitution results
      in loss of SEC23A function. A phenotype reminiscent of CLSD is observed in
      zebrafish embryos injected with sec23a-blocking morpholinos. Our observations
      suggest that disrupted endoplasmic reticulum export of the secretory proteins
      required for normal morphogenesis accounts for CLSD.

PMID- 16980980
TI  - B lymphocytes from early vertebrates have potent phagocytic and microbicidal
      abilities.
AB  - The present paradigm dictates that phagocytosis is accomplished mainly by
      'professional' phagocytes (such as macrophages and monocytes), whereas B cells
      lack phagocytic capabilities. Here we demonstrate that B cells from teleost fish
      have potent in vitro and in vivo phagocytic activities. Particle uptake by B
      cells induced activation of 'downstream' degradative pathways, leading to
      'phagolysosome' formation and intracellular killing of ingested microbes. Those
      results indicate a previously unknown function for B cells in the innate immunity
      of these primitive animals. A considerable proportion of Xenopus laevis B cells
      were also phagocytic. Our findings support the idea that B cells evolved from an
      ancestral phagocytic cell type and provide an evolutionary framework for
      understanding the close relationship between mammalian B lymphocytes and
      macrophages.

PMID- 16980982
TI  - Cytokines, p38 MAP kinase and the pathophysiology of depression.

PMID- 16980981
TI  - Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide
      response.
AB  - At mammalian body temperature, the plague bacillus Yersinia pestis synthesizes
      lipopolysaccharide (LPS)-lipid A with poor Toll-like receptor 4 (TLR4)
      stimulating activity. To address the effect of weak TLR4 stimulation on
      virulence, we modified Y. pestis to produce a potent TLR4-stimulating LPS.
      Modified Y. pestis was completely avirulent after subcutaneous infection even at
      high challenge doses. Resistance to disease required TLR4, the adaptor protein
      MyD88 and coreceptor MD-2 and was considerably enhanced by CD14 and the adaptor
      Mal. Both innate and adaptive responses were required for sterilizing immunity
      against the modified strain, and convalescent mice were protected from both
      subcutaneous and respiratory challenge with wild-type Y. pestis. Despite the
      presence of other established immune evasion mechanisms, the modified Y. pestis
      was unable to cause systemic disease, demonstrating that the ability to evade the
      LPS-induced inflammatory response is critical for Y. pestis virulence. Evading
      TLR4 activation by lipid A alteration may contribute to the virulence of various
      Gram-negative bacteria.

PMID- 16980985
TI  - Is hunger a driver of the cognitive development?

PMID- 16980988
TI  - Mismatch of minor histocompatibility antigen contributes to a graft-versus
      leukemia effect rather than to acute GVHD, resulting in long-term survival after
      HLA-identical stem cell transplantation in Japan.
AB  - We determined the alleles of five polymorphic molecules including HA-1 and four
      adhesion molecules for 106 patients transplanted with HLA-identical stem cell
      grafts and investigated the association of mismatches as correlates of relapse
      and graft-versus-host disease (GVHD). All 106 recipients underwent stem cell
      transplantation (SCT) after myeloablative conditioning between 1985 and 2002.
      Risk status of disease at SCT was standard (n=63) and high (n=42). After SCT, 36,
      49 and 33 developed acute GVHD, chronic GVHD and relapsed, respectively. Our
      patients relapsed at rates of 16.7 and 38.6% with one or more and without
      incompatibilities (P=0.013). The relapse rates of patients with CD62L, CD31 codon
      563, CD31 codon 125, HA-1 and CD49b incompatibilities were 5.9, 11.8, 15.4, 16.0
      and 33.3%, respectively. The frequency of acute GVHD did not differ regardless of
      incompatibilities. In standard-risk group, the accumulated relapse rates of 19
      and 44 patients with and without minor histocompatibility antigen incompatibility
      were 22% and unexpectedly 66%, respectively (P=0.02). The probability of 12-year
      survival was 88% in the former and 66% in the latter patients (P=0.03). Our data
      suggest that incompatibility of CD62L, CD31 codon 563 and CD31 codon 125
      contributes to a graft-versus-leukemia effect rather than to GVHD, resulting in
      prolonged survival after HLA-identical SCT.

PMID- 16980989
TI  - Retrospective utility of bronchoscopy after hematopoietic stem cell transplant.
AB  - Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is thought to be the
      procedure of choice to evaluate pulmonary infiltrates in hematopoietic stem cell
      transplant (HSCT) recipients. We retrospectively reviewed 91 bronchoscopies
      performed on 190 in-patient HSCT recipients admitted or treated for pneumonia
      from January 1994 to December 2004. These yielded a diagnosis 49% of the time
      with an overall survival of 35 days post-bronchoscopy. We were unable to detect
      any survival benefit from an addition to the treatment regimen after a positive
      result from analysis of the BAL fluid or transbronchial biopsy. The most common
      bacteria isolated was Pseudomonas that was often resistant to the patient's
      current antibiotics, suggesting that in lieu of this diagnostic procedure,
      changes to better cover resistant Gram-negative bacteria are reasonable. Although
      transbronchial biopsies provided an additional diagnosis in one out of 21
      biopsies performed, six of the seven complications in our series were directly
      related to the transbronchial biopsy. With approximately a 50% yield from a
      bronchoscopy, additional treatment given after only 20% of all bronchoscopies,
      and no detectable survival benefit with a bronchoscopy that yielded a diagnosis,
      the utility of a bronchoscopy in this patient population is questioned by these
      data.

PMID- 16980990
TI  - Rapid and massive expansion of cord blood-derived cytokine-induced killer cells:
      an innovative proposal for the treatment of leukemia relapse after cord blood
      transplantation.
AB  - We have used a standardized 21-day expansion protocol to produce cytokine-induced
      killer (CIK) cells starting from very small amounts of nucleated cells
      (approximately 15 x 10(6) cells) isolated from cord blood. Mononuclear cells are
      stimulated with anti CD3 (OKT3) and IFNgamma and then expanded with IL-2.
      Moreover, we show that washouts of cord blood units bags (at the end of the
      infusion) may be sufficient to yield almost 500 x 10(6) CIK by the same expansion
      protocol. CIK cells show strong cytotoxic activity against a variety of tumor
      target cell lines including B and T lymphomas and myeloid leukemias. More
      importantly, expanded cord blood-derived CIK cells are cytotoxic against fresh
      leukemic blasts and express perforin, granzyme and NKG2D molecule at high levels.
      The same in vitro protocol has already been used to expand CIK cells from
      peripheral blood of adult donors under GMP conditions and therefore these
      observations open up the possibility of imagining a future clinical application
      of leukemia relapse following cord blood transplantation with CIK cells obtained
      from the same cord blood unit.

PMID- 16980991
TI  - Overnight storage of autologous stem cell apheresis products before
      cryopreservation does not adversely impact early or long-term engraftment
      following transplantation.
AB  - To reduce costs and avoid inconvenient overtime work, our institution changed
      policy in September 2000 so that autologous stem cell apheresis products were
      stored overnight before cryopreservation rather than immediately processed. This
      retrospective review was conducted to evaluate the possible impact of this policy
      change on hematopoietic engraftment following autologous stem cell
      transplantation (ASCT). In total, 229 consecutive lymphoma patients who underwent
      a single, unpurged ASCT in Calgary between January 1995 and November 2003 were
      evaluated. Of these patients, 131 patients' autografts underwent immediate
      processing and cryopreservation before September 2000, and 98 patients'
      autografts underwent next-day cryopreservation after overnight storage following
      this date. Results of univariate and multivariate analyses demonstrated no
      adverse effect of overnight storage before cryopreservation on the number of days
      to initial engraftment of platelets or neutrophils, on the proportion of patients
      with low blood counts 6 months post-ASCT, or on lymphoma relapse rates or overall
      survival post-ASCT. These data suggest that overnight storage of the autograft
      before cryopreservation does not adversely affect graft viability or influence
      long-term disease status, and support the continued use of overnight storage of
      stem cells before cryopreservation as a convenient, cost reduction measure.

PMID- 16980992
TI  - Graft-versus-host and graft-versus-leukemia reactions: a summary of the Seventh
      International Symposium held in Garmisch-Partenkirchen, Germany, February 22nd
      25th, 2006, Tolerance and Immunity, an update on lymphoid malignancies.
AB  - The Seventh International Symposium on graft-versus-host and graft-versus
      leukemia reactions was held in Garmisch Partenkirchen (Germany, near Lake
      Riessersee) between January 22nd and 25th, 2006. A total of more than 100 invited
      participants (scientists and clinicians working in the area of allogeneic stem
      cell transplantation) discussed research in the area of lymphoid malignancies.
      Major topics of the 2006 meeting were lymphocyte biology, experimental systems,
      lymphoma pathogenesis, cellular therapy in vivo and vitro, idiotype-specific
      responses and graft-versus-malignancy reactions for lymphomas and multiple
      myeloma. Further highlights were immune responses to blasts of ALL,
      haploidentical transplantation, role of natural killer cells, clinical guidelines
      for allogeneic transplantation and adoptive immunotherapy in chronic lymphocytic
      leukemia and multiple myeloma, new antibody-mediated strategies. As can be seen
      in the summaries of the individual presentations, progress was made in the
      understanding of lymphoma biology and in the clinical application of graft-versus
      lymphoma or graft-versus-myeloma effects. Each day was followed by round-table
      discussions, which summarized new data and challenged established concepts. The
      discussions resulted in new insights and projects for basic research and clinical
      transplantation.

PMID- 16980993
TI  - Successful stem cell transplantation in an infant with severe congenital
      neutropenia complicated by pretransplant inflammatory pseudotumor of the liver.

PMID- 16980994
TI  - Chronic graft-versus-host disease: implications of the National Institutes of
      Health consensus development project on criteria for clinical trials.
AB  - Chronic graft-versus-host disease (GVHD) has been a difficult problem to address
      and clinical research in this area lags behind other innovations in hematopoietic
      stem cell transplantation (HCT). Recently the international transplant community
      has focused more on chronic GVHD. This new focus is well represented by the
      development of the National Institutes of Health sponsored chronic GVHD consensus
      project, which has unified the transplant community's approach to chronic GVHD
      through the activities of focused working groups. From December 2005 through May
      2006, a series of consensus documents have been published addressing the areas of
      diagnosis and staging, histopathology, strategies for the development and
      validation of biomarkers, response criteria, ancillary therapy and supportive
      care and the design of clinical trials. This paper summarizes and discusses these
      reports, focusing specifically on diagnosis and scoring and response criteria.
      Although these documents represent a huge effort by the research community, they
      must be prospectively implemented and validated. These new criteria should
      advance the standards and uniformity of chronic GVHD clinical research. The
      ultimate success of this project is dependent on whether these recommendations
      move the field forward. This is an opportunity for the transplant community to
      unite and make a significant impact in chronic GVHD.

PMID- 16980995
TI  - Comparable kinetics of myeloablation between fludarabine/full-dose busulfan and
      fludarabine/melphalan conditioning regimens in allogeneic peripheral blood stem
      cell transplantation.
AB  - Fludarabine was utilized in the conditioning regimen of 30 adult patients
      undergoing an allogeneic hematopoietic stem cell transplant. In 18 patients it
      was combined with full-dose busulfan (FluBu) as a myeloablative regimen and in 12
      cases with melphalan (FluMel) as a reduced intensity conditioning (RIC) regimen.
      Patients in the FluBu group were younger than in the FluMel group (P=0.03). Of 30
      patients, 24 received peripheral blood stem cells (PBSC) whereas six patients in
      the FluBu group received bone marrow cells. The hematological toxicity of each
      regimen was evaluated by analyzing the kinetics of the neutropenia induced by
      preparative regimens and the time to recovery of the absolute neutrophils count
      (ANC) and platelets post transplantation. In PBSC transplants, the median day of
      severe neutropenia (<500 ANC/microl) occurred on day +6 after the FluBu regimen
      and on day +3 after FluMel (P=ns), whereas both groups had a duration of severe
      neutropenia of 9 days and a comparable time for ANC and platelet engraftment.
      Extra-hematological toxicities were also comparable in the two groups. These
      findings suggest that the hematological and extra-hematological toxicities
      induced by fludarabine/full-dose i.v. busulfan are similar to those induced by a
      standard RIC regimen such as fludarabine/melphalan.

PMID- 16980996
TI  - Clinical outcomes and direct hospital costs of reduced-intensity allogeneic
      transplantation in chronic myeloid leukemia.
AB  - A reduced-intensity conditioning allogeneic stem cell transplantation was given
      to 19 patients (aged 15-59 years) in the first chronic phase and one patient in
      the accelerated phase with chronic myeloid leukemia (CML) after a regimen
      consisting of fludarabine (Flu), busulfan (Bu) and ATG Fresenius. The median
      follow-up was 27 months. Until day +100, no transplant-related mortality was
      recorded. The incidence of acute and chronic graft-versus-host disease (GvHD) was
      55 and 75%, respectively. Two patients (10%) died from GvHD. Fourteen (70%)
      patients achieved molecular remission. Additional post-transplant intervention
      (donor lymphocyte infusion, imatinib) was necessary, however, in 10 patients (50%
      of the patients; non-achievement of stable molecular remission or later
      relapses). The total direct cost of the transplantation treatment for all of the
      patients came to 1,572,880 euro. If the patients had been treated with imatinib
      and followed-up with the same time period as they were following a
      transplantation, the direct cost of the imatinib treatment would have been
      2,005,117 euro. The transplantation treatment appears to be less expensive after
      approximately 2 years of follow-up. Flu+Bu+ATG is a low-toxicity regimen for
      patients with CML. However, a close follow-up is necessary and about 50% of the
      patients require further therapeutic intervention.

PMID- 16980997
TI  - Phase I/II trial of multicycle high-dose chemotherapy with peripheral blood stem
      cell support for treatment of advanced ovarian cancer.
AB  - Ovarian cancer is chemosensitive, but most patients with advanced disease die
      from tumor progression. As 25% of the patients can be cured by chemotherapy, it
      is reasonable to evaluate high-dose chemotherapy (HDCT). Forty-eight patients
      with untreated ovarian cancer were entered in a multicenter phase I/II trial of
      multicycle HDCT. Median age was 46 (19-59 years); International Federation of
      Gynecology and Obstetrics-stage was III in 79% and IV in 21%; 31% had residual
      disease >1 cm after surgery. Two courses of induction/mobilization therapy with
      cyclophosphamide (250 mg/m2) and paclitaxel (250 mg/m2) were used to collect
      peripheral blood stem cells. HDCT consisted of two courses of carboplatin (area
      under curve (AUC) 18-22) and paclitaxel followed by one course of carboplatin and
      melphalan (140 mg/m2) with or without etoposide (1600 mg/m2). Main toxicity was
      gastrointestinal. Limiting carboplatin to AUC 20 and eliminating etoposide
      resulted in manageable toxicity (69% without grade 3/4 toxicity). One patient
      died from treatment-related pneumonitis. At 8 years median follow-up, median
      progression-free-survival (PFS) and overall survival (OS) is 13.3 and 37.0
      months. Five-years PFS and OS is 18 and 33%. Multicycle HDCT is feasible in a
      multicenter setting. A European phase III trial based on this regimen is
      evaluating the efficacy of HDCT.

PMID- 16980998
TI  - Oral mucositis in myeloma patients undergoing melphalan-based autologous stem
      cell transplantation: incidence, risk factors and a severity predictive model.
AB  - Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy
      for multiple myeloma, but is associated with severe oral mucositis (OM). To
      identify predictors for severe OM, we studied 381 consecutive newly diagnosed
      myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body
      surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential
      covariates included demographics, pre-transplant serum albumin and renal and
      liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted
      in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of
      patients and was severe in 21%. Predictors of severe OM in multiple logistic
      regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95%
      confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan
      (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed
      based on these variables. We concluded that BSA dosing of melphalan results in
      wide variations in the mg/kg dose, and that patients with renal dysfunction who
      are scheduled to receive a high mg/kg melphalan dose have the greatest risk for
      severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are
      needed to better understand interpatient variability of melphalan exposure and
      toxicity.

PMID- 16980999
TI  - Plasma antioxidants in subjects before hematopoietic stem cell transplantation.
AB  - Chemo-irradiation induced oxidative damage to vascular endothelium may contribute
      to pulmonary complications of hematopoietic stem cell transplantation (HSCT). We
      measured antioxidants, markers of oxidative stress and plasma antioxidant
      capacity in plasma or serum from 24 subjects at day 7 before HSCT and 20 control
      subjects. The plasma concentration of extracellular glutathione peroxidase (GPX
      3) was significantly reduced in the HSCT subjects compared with controls (HSCT:
      98+/-42 microg/ml, control: 169+/-56 microg/ml, P<0.0001). The concentration of
      gamma-tocopherol was significantly higher in the HSCT subjects compared with
      controls (HSCT: 207+/-103 microg/dl; CONTROL: 98+/-52 microg/dl; P=0.0002). The
      plasma concentrations of protein carbonyl, nitrotyrosine, malondialdehyde, alpha
      tocopherol, vitamin A, homocysteine, cysteine and cysteinylglycine did not differ
      between HSCT and control subjects. Plasma from HSCT subjects was as effective as
      control plasma in quenching menadione-induced intracellular reactive oxygen
      species production in human microvascular endothelial cells. In summary, subjects
      before HSCT have significantly reduced plasma concentrations of GPX-3, elevated
      plasma gamma-tocopherol yet retains the ability to quench an acute oxidative
      stress. These changes may play a role in chronic oxidative stress in the HSCT
      population.

PMID- 16981000
TI  - Cyclosporine short infusion and C2 monitoring in haematopoietic stem cell
      transplant recipients.
AB  - Blood concentrations of cyclosporine A (CsA) >or=800 microg/l measured 2 h post
      dosing, the C2 concentration, is necessary to obtain a maximal pharmacological
      effect and correlates well with transplant-related complications such as
      transplant rejection and toxicity. In an open crossover study CsA blood levels
      were measured during 24 h to generate a pharmacokinetic profile on days 1, 8 and
      15 after starting CsA infusion in 21 haematopoietic allogeneic stem cell
      transplant recipients who were receiving intravenously CsA 3 mg/kg/day either by
      continuous infusion or by 2 h infusion given every 12 h. C2 levels after the 2 h
      infusion correlated better than C1 or C3 levels with the area under the
      concentration-time curve from 0 to 4 h (r2=0.62). C2 levels >or=800 microg/l were
      also achieved for 20 out of 24 (83%) of cases after the 2 h infusion of CsA
      without any increase of CsA-related toxicity but for only three of the 23
      patients (13%) after continuous infusion. Therefore, we recommend CsA infusions
      in 2 h during transplant and perform C2 monitoring to obtain therapeutic C2
      levels >or=800 microg/l.

PMID- 16981001
TI  - Activation of mouse protease-activated receptor-2 induces lymphocyte adhesion and
      generation of reactive oxygen species.
AB  - BACKGROUND AND PURPOSE: Protease-activated receptor-2 (PAR-2) is expressed on
      lymphocytes and endothelial cells, and plays a significant role in inflammatory
      reactions. Since leukocyte-endothelial cell interaction and reactive oxygen
      species (ROS) generation are hallmarks of the development of inflammation, the
      effects of PAR-2 activation by trypsin on lymphocyte adhesion and ROS generation
      was examined utilising PAR-2 wild type and knockout (PAR-2-/-) mice. EXPERIMENTAL
      APPROACH: Lymphocyte adhesion to the luminal surface of mouse isolated aortae was
      measured using 51Cr-labelled leukocytes and ROS generation from isolated
      lymphocytes was quantified using chemiluminescence. KEY RESULTS: Trypsin induced
      adhesion of lymphocytes when added exogenously to the endothelial surface of the
      aorta for 30 min. Similarly, increased lymphocyte adhesion was also observed when
      mice were injected with trypsin intravenously 24 h prior to the adhesion assay,
      an effect which was partly ICAM-1 mediated. Trypsin also increased ROS generation
      from isolated mouse lymphocytes in a dose-dependent manner. The increase in
      lymphocyte adhesion and ROS production in response to trypsin were abolished in
      PAR-2-/- mice indicating a PAR-2 dependent mechanism. Superoxide dismutase had a
      greater inhibitory effect in PAR-2-/- mice compared to wild type mice when
      lymphocytes were stimulated with PMA but not trypsin. CONCLUSIONS AND
      IMPLICATIONS: The present study indicates that activation of PAR-2 may be an
      important factor in modulating lymphocyte adhesion and ROS generation. The
      results have implications for developing anti-inflammatory strategies.

PMID- 16981002
TI  - Multiple drugbinding sites on the R482G isoform of the ABCG2 transporter.
AB  - BACKGROUND & PURPOSE: Drug-resistant cancer cells frequently display efflux pumps
      such as P-glycoprotein (P-gp), the multidrug resistance associated protein (MRP1)
      or the transporter ABCG2. These transporters are each capable of mediating the
      active efflux of numerous anticancer drugs and display relatively distinct
      substrate preferences. The last, most recently discovered member, ABCG2, plays a
      major role in resistance in several types of cancer and the precise pharmacology
      of this multidrug transporter remain unresolved as does the nature of substrate
      binding. EXPERIMENTAL APPROACH: Plasma membranes from insect cells expressing
      ABCG2 were used to characterise binding of [3H]daunomycin to the multidrug
      transporter. The kinetics of association and dissociation for this substrate and
      several other compounds were also determined in this experimental system. KEY
      RESULTS: The dissociation constant for [3H]daunomycin binding was 564 +/- 57 nM
      and a Hill slope of 1.4 suggested cooperative binding. Doxorubicin, prazosin and
      daunomycin completely displaced the binding of radioligand, while mitoxantrone
      and Hoechst 33342 produced only a partial displacement. Analysis of the
      dissociation rates revealed that [3H]daunomycin and doxorubicin bind to multiple
      sites on the transporter. CONCLUSIONS: Both kinetic and equilibrium data support
      the presence of at least two symmetric drug binding sites on ABCG2, which is
      distinct from the asymmetry observed for P-gp. The data provide the first
      molecular details underlying the mechanism by which this transporter is capable
      of interacting with multiple substrates.

PMID- 16981003
TI  - Regional vascular responses to ATP and ATP analogues in the rabbit kidney in
      vivo: roles for adenosine receptors and prostanoids.
AB  - BACKGROUND AND PURPOSE: Our knowledge of the effects of P2-receptor activation on
      renal vascular tone comes mostly from in vitro models. We aimed to characterise
      the pharmacology of ATP in the renal circulation in vivo. EXPERIMENTAL APPROACH:
      In pentobarbitone anaesthetized rabbits, we examined total renal and medullary
      vascular responses to ATP (0.2 and 0.8 mg kg(-1)), beta, gamma-methylene ATP
      (beta, gamma-mATP, 7 and 170 microg kg(-1)), alpha, beta-mATP (0.2 and 2 microg
      kg(-1)) and adenosine (2 and 6 microg kg(-1)) using transit-time ultrasound and
      laser Doppler flowmetry, respectively. We also determined whether adenosine
      receptors, NO or prostanoids contribute to the actions of the purinoceptor
      agonists. KEY RESULTS: Renal arterial boluses of ATP, beta,gamma-mATP, and
      adenosine produced biphasic changes; ischaemia followed by hyperaemia, in total
      renal and medullary blood flow. alpha,beta-mATP induced only ischaemia. The
      adenosine receptor antagonist 8-(p-sulphophenyl)theophylline reduced the
      responses to adenosine and the hyperaemic responses to ATP and beta,gamma-mATP
      only. NO synthase inhibition (Nomega-nitro-L-arginine) did not significantly
      alter responses to the P2 receptor agonists. Subsequent cyclooxygenase inhibition
      (ibuprofen) reduced the ATP- and beta, gamma-mATP-induced increases in renal
      blood flow. All other responses remained unchanged. CONCLUSIONS AND IMPLICATIONS:
      In the rabbit kidney in vivo, alpha, beta-mATP sensitive receptors mediate
      vasoconstriction. beta,gamma-mATP and ATP induce vasodilation at least partly
      through adenosine receptors. ATP induced renal vasodilatation is independent of
      NO and partly dependent on prostanoids in the bulk of the kidney, but not in the
      vasculature controlling medullary blood flow.

PMID- 16981005
TI  - Small molecules with antimicrobial activity against E. coli and P. aeruginosa
      identified by high-throughput screening.
AB  - BACKGROUND AND PURPOSE: New antimicrobials are needed because of the emergence of
      organisms that are resistant to available antimicrobials. The purpose of this
      study was to evaluate a high-throughput screening approach to identify
      antibacterials against two common disease-causing bacteria, and to determine the
      frequency, novelty, and potency of compounds with antibacterial activity.
      EXPERIMENTAL APPROACH: A high-throughput, turbidometric assay of bacterial growth
      in a 96-well plate format was used to screen a diverse collection of 150,000
      small molecules for antibacterial activity against E. coli and P. aeruginosa. The
      statistical Z'-factor for the assay was > or = 0.7. KEY RESULTS: Screening for
      inhibition of E. coli growth gave a 'hit' rate (> 60% inhibition at 12.5 microM)
      of 0.025%, which was more than 5-fold reduced for P. aeruginosa. The most potent
      antibacterials (EC50 < 0.5 microM) were of the nitrofuran class followed by
      naphthalimide, salicylanilide, bipyridinium and quinoazolinediamine chemical
      classes. Screening of > 250 analogs of the most potent antibacterial classes
      established structure-activity data sets. CONCLUSIONS AND IMPLICATIONS: Our
      results validate and demonstrate the utility of a growth-based phenotype screen
      for rapid identification of small-molecule antibacterials. The favourable
      efficacy and structure-activity data for several of the antibacterial classes
      suggests their potential development for clinical use.

PMID- 16981006
TI  - Promotion of axonal maturation and prevention of memory loss in mice by extracts
      of Astragalus mongholicus.
AB  - BACKGROUND AND PURPOSE: Neurons with atrophic neurites may remain alive and
      therefore may have the potential to regenerate even when neuronal death has
      occurred in some parts of the brain. This study aimed to explore effects of drugs
      that can facilitate the regeneration of neurites and the reconstruction of
      synapses even in severely damaged neurons. EXPERIMENTAL APPROACH: We investigated
      the effects of extracts of Astragalus mongholicus on the cognitive defect in mice
      caused by injection with the amyloid peptide Abeta(25-35). We also examined the
      effect of the extract on the regeneration of neurites and the reconstruction of
      synapses in cultured neurons damaged by Abeta(25-35). KEY RESULTS: A. mongholicus
      extract (1 g kg(-1) day(-1) for 15 days, p.o.) reversed Abeta(25-35)-induced
      memory loss and prevented the loss of axons and synapses in the cerebral cortex
      and hippocampus in mice. Treatment with Abeta(25-35) (10 microM) induced axonal
      atrophy and synaptic loss in cultured rat cortical neurons. Subsequent treatment
      with A. mongholicus extract (100 microg/ml) resulted in significant axonal
      regeneration, reconstruction of neuronal synapses, and prevention of Abeta(25-35)
      induced neuronal death. Similar extracts of A. membranaceus had no effect on
      axonal atrophy, synaptic loss, or neuronal death. The major known components of
      the extracts (astragalosides I, II, and IV) reduced neurodegeneration, but the
      activity of the extracts did not correlate with their content of these three
      astragalosides. CONCLUSION AND IMPLICATIONS: A. mongholicus is an important
      candidate for the treatment of memory disorders and the main active constituents
      may not be the known astragalosides.

PMID- 16981004
TI  - Cholinergic regulation of epithelial ion transport in the mammalian intestine.
AB  - Acetylcholine (ACh) is critical in controlling epithelial ion transport and hence
      water movements for gut hydration. Here we review the mechanism of cholinergic
      control of epithelial ion transport across the mammalian intestine. The
      cholinergic nervous system affects basal ion flux and can evoke increased active
      ion transport events. Most studies rely on measuring increases in short-circuit
      current (ISC = active ion transport) evoked by adding ACh or cholinomimetics to
      intestinal tissue mounted in Ussing chambers. Despite subtle species and gut
      regional differences, most data indicate that, under normal circumstances, the
      effect of ACh on intestinal ion transport is mainly an increase in Cl- secretion
      due to interaction with epithelial M3 muscarinic ACh receptors (mAChRs) and, to a
      lesser extent, neuronal M1 mAChRs; however, AChR pharmacology has been plagued by
      a lack of good receptor subtype-selective compounds. Mice lacking M3 mAChRs
      display intact cholinergically-mediated intestinal ion transport, suggesting a
      possible compensatory mechanism. Inflamed tissues often display perturbations in
      the enteric cholinergic system and reduced intestinal ion transport responses to
      cholinomimetics. The mechanism(s) underlying this hyporesponsiveness are not
      fully defined. Inflammation-evoked loss of mAChR-mediated control of epithelial
      ion transport in the mouse reveals a role for neuronal nicotinic AChRs,
      representing a hitherto unappreciated braking system to limit ACh-evoked Cl-
      secretion. We suggest that: i) pharmacological analyses should be supported by
      the use of more selective compounds and supplemented with molecular biology
      techniques targeting specific ACh receptors and signalling molecules, and ii)
      assessment of ion transport in normal tissue must be complemented with
      investigations of tissues from patients or animals with intestinal disease to
      reveal control mechanisms that may go undetected by focusing on healthy tissue
      only.

PMID- 16981007
TI  - Mll partial tandem duplication induces aberrant Hox expression in vivo via
      specific epigenetic alterations.
AB  - We previously identified a rearrangement of mixed-lineage leukemia (MLL) gene
      (also known as ALL-1, HRX, and HTRX1), consisting of an in-frame partial tandem
      duplication (PTD) of exons 5 through 11 in the absence of a partner gene,
      occurring in approximately 4%-7% of patients with acute myeloid leukemia (AML)
      and normal cytogenetics, and associated with a poor prognosis. The mechanism by
      which the MLL PTD contributes to aberrant hematopoiesis and/or leukemia is
      unknown. To examine this, we generated a mouse knockin model in which exons 5
      through 11 of the murine Mll gene were targeted to intron 4 of the endogenous Mll
      locus. Mll(PTD/WT) mice exhibit an alteration in the boundaries of normal
      homeobox (Hox) gene expression during embryogenesis, resulting in axial skeletal
      defects and increased numbers of hematopoietic progenitor cells. Mll(PTD/WT) mice
      overexpress Hoxa7, Hoxa9, and Hoxa10 in spleen, BM, and blood. An increase in
      histone H3/H4 acetylation and histone H3 lysine 4 (Lys4) methylation within the
      Hoxa7 and Hoxa9 promoters provides an epigenetic mechanism by which this
      overexpression occurs in vivo and an etiologic role for MLL PTD gain of function
      in the genesis of AML.

PMID- 16981008
TI  - Reduced maternal expression of adrenomedullin disrupts fertility, placentation,
      and fetal growth in mice.
AB  - Adrenomedullin (AM) is a multifunctional peptide vasodilator that is essential
      for life. Plasma AM expression dramatically increases during pregnancy, and
      alterations in its levels are associated with complications of pregnancy
      including fetal growth restriction (FGR) and preeclampsia. Using AM+/- female
      mice with genetically reduced AM expression, we demonstrate that fetal growth and
      placental development are seriously compromised by this modest decrease in
      expression. AM+/- female mice had reduced fertility characterized by FGR. The
      incidence of FGR was also influenced by the genotype of the embryo, since AM-/-
      embryos were more often affected than either AM+/- or AM+/+ embryos. We
      demonstrate that fetal trophoblast cells and the maternal uterine wall have
      coordinated and localized increases in AM gene expression at the time of
      implantation. Placentas from growth-restricted embryos showed defects in
      trophoblast cell invasion, similar to defects that underlie human preeclampsia
      and placenta accreta. Our data provide a genetic in vivo model to implicate both
      maternal and, to a lesser extent, embryonic levels of AM in the processes of
      implantation, placentation, and subsequent fetal growth. This study provides the
      first genetic evidence to our knowledge to suggest that a modest reduction in
      human AM expression during pregnancy may have an unfavorable impact on
      reproduction.

PMID- 16981010
TI  - TNF-alpha downregulates eNOS expression and mitochondrial biogenesis in fat and
      muscle of obese rodents.
AB  - Obesity is associated with chronic low-grade inflammation. Thus, at metabolically
      relevant sites, including adipose tissue and muscle, there is abnormal production
      of proinflammatory cytokines such as TNF-alpha. Here we demonstrate that eNOS
      expression was reduced, with a concomitant reduction of mitochondrial biogenesis
      and function, in white and brown adipose tissue and in the soleus muscle of 3
      different animal models of obesity. The genetic deletion of TNF receptor 1 in
      obese mice restored eNOS expression and mitochondrial biogenesis in fat and
      muscle; this was associated with less body weight gain than in obese wild-type
      controls. Furthermore, TNF-alpha downregulated eNOS expression and mitochondrial
      biogenesis in cultured white and brown adipocytes and muscle satellite cells of
      mice. The NO donors DETA-NO and SNAP prevented the reduction of mitochondrial
      biogenesis observed with TNF-alpha. Our findings demonstrate that TNF-alpha
      impairs mitochondrial biogenesis and function in different tissues of obese
      rodents by downregulating eNOS expression and suggest a novel pathophysiological
      process that sustains obesity.

PMID- 16981009
TI  - Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of
      autoimmune arthritis.
AB  - Tyrosine kinases play a central role in the activation of signal transduction
      pathways and cellular responses that mediate the pathogenesis of rheumatoid
      arthritis. Imatinib mesylate (imatinib) is a tyrosine kinase inhibitor developed
      to treat Bcr/Abl-expressing leukemias and subsequently found to treat c-Kit
      expressing gastrointestinal stromal tumors. We demonstrate that imatinib potently
      prevents and treats murine collagen-induced arthritis (CIA). We further show that
      micromolar concentrations of imatinib abrogate multiple signal transduction
      pathways implicated in RA pathogenesis, including mast cell c-Kit signaling and
      TNF-alpha release, macrophage c-Fms activation and cytokine production, and
      fibroblast PDGFR signaling and proliferation. In our studies, imatinib attenuated
      PDGFR signaling in fibroblast-like synoviocytes (FLSs) and TNF-alpha production
      in synovial fluid mononuclear cells (SFMCs) derived from human RA patients.
      Imatinib-mediated inhibition of a spectrum of signal transduction pathways and
      the downstream pathogenic cellular responses may provide a powerful approach to
      treat RA and other inflammatory diseases.

PMID- 16981013
TI  - Synthesis and Characterization of a Novel Gd(III)-Cu(II) Dinuclear Adduct.
AB  - Two novel Gd(III)-Cu(II) dinuclear complexes have been prepared by the acid-base
      reaction between Gd(hfa)(3) and Cu(2,2-oxomac) (1, Cu(2,2-oxomac)Gd(hfa)(3)) and
      between Gd(hfa)(3) and Cu(3,2-oxomac) (2, Cu(3,2-oxomac)Gd(hfa)(3)). These
      complexes have been characterized by elemental analysis and infrared
      spectroscopy. The structure of 1 has been determined by X-ray diffraction. The
      copper atom is square pyramidal, bound to the four planar nitrogen atoms of the
      macrocycle and weakly bound to the oxygen atom of a dimethylformamide (dmf)
      molecule. The gadolinium atom is at the center of a tricapped trigonal prism. The
      nine-coordinate gadolinium atom is bound to six oxygen atoms of three hfa
      ligands, the two oxamide oxygen atoms of the copper macrocycle, and one oxygen
      atom of a second coordinated dmf molecule. Unsymmetric binding of the copper
      macrocycle to gadolinium leads to a distortion in the bridging atoms not observed
      in reactions of the copper macrocycles with transition metal hfa's. GRAPHICAL
      ABSTRACT: The reaction of Cu(2,2-oxomac) with Gd(hfa)(3) yields a Gd(III)-Cu(II)
      dinuclear complex with an oxamide bridge between copper(II) and gadolinium(III).
      The gadolinium atom adopts a tricapped trigonal prismatic geometry.

PMID- 16981011
TI  - Androgen-dependent pathology demonstrates myopathic contribution to the Kennedy
      disease phenotype in a mouse knock-in model.
AB  - Kennedy disease, a degenerative disorder characterized by androgen-dependent
      neuromuscular weakness, is caused by a CAG/glutamine tract expansion in the
      androgen receptor (Ar) gene. We developed a mouse model of Kennedy disease, using
      gene targeting to convert mouse androgen receptor (AR) to human sequence while
      introducing 113 glutamines. AR113Q mice developed hormone and glutamine length
      dependent neuromuscular weakness characterized by the early occurrence of
      myopathic and neurogenic skeletal muscle pathology and by the late development of
      neuronal intranuclear inclusions in spinal neurons. AR113Q males unexpectedly
      died at 2-4 months. We show that this androgen-dependent death reflects decreased
      expression of skeletal muscle chloride channel 1 (CLCN1) and the skeletal muscle
      sodium channel alpha-subunit, resulting in myotonic discharges in skeletal muscle
      of the lower urinary tract. AR113Q limb muscles show similar myopathic features
      and express decreased levels of mRNAs encoding neurotrophin-4 and glial cell line
      derived neurotrophic factor. These data define an important myopathic
      contribution to the Kennedy disease phenotype and suggest a role for muscle in
      non-cell autonomous toxicity of lower motor neurons.

PMID- 16981014
TI  - The spouse situation inventory: a role-play measure of coping skills in women
      with alcoholic partners.
AB  - This article reports on the psychometric evaluation of the Spouse Situation
      Inventory (SSI), a role-play measure of coping skills in women with alcoholic
      partners. The study examined the generalizability, alternate form reliability,
      test-retest reliability, and construct validity of the measure in 472 women from
      both treatment and nontreatment populations. The SSI had acceptable
      generalizability and reliability. SSI performance also had predicted
      relationships with measures of general escape coping, alcohol-related coping
      behaviors, the woman's drinking, the partner's drinking in the treatment group,
      and the partner's problem recognition in the nontreatment group. The SSI shows
      promise as a reliable and valid measure of coping skills in this population and
      has direct implications for development and evaluation of skill training
      programs.

PMID- 16981015
TI  - EPR spectroscopy as a probe of metal centres in biological systems.
AB  - Molecular paramagnetism pervades the bioinorganic chemistry of V, Mn, Fe, Co, Ni,
      Cu, Mo, W, and of a number of non-biological transition elements. To date we can
      look back at half a century of fruitful EPR studies on metalloproteins, and
      against this background evaluate the significance of modern EPR spectroscopy from
      the perspective of a biochemist, making a distinction between conventional
      continuous wave X-band spectroscopy as a reliable work horse with broad,
      established applicability even on crude preparations, vs. a diffuse set of
      "advanced EPR" technologies whose practical application typically calls for
      narrowly focused research hypotheses and very high quality samples. The type of
      knowledge on metalloproteins that is readily obtainable with EPR spectroscopy, is
      explained with illustrative examples, as is the relation between experimental
      complexity and the spin value of the system.

PMID- 16981016
TI  - Copper-mediated cleavage of disulfides by tertiary phosphines: a new route to As
      S anions.
AB  - The synthesis of [(PhAs)2(micro-S2)(micro-S)] and its reactions to form novel
      Cu(I) complexes are reported, together with a new cleavage reaction of disulfides
      by Cu(I) thiolates and tertiary phosphines.

PMID- 16981017
TI  - Double half-cubane copper(II) complexes available from copper(II) 1,1,1,5,5,5
      hexafluoropentane-2,4-dionate dissolved in formamides.
AB  - Tetranuclear copper(II) complexes were obtained after simply dissolving
      [Cu(hfac)2] in formamide-methanol mixed solvents (Hhfac=1,1,1,5,5,5
      hexafluoropentane-2,4-dione). X-Ray diffraction studies revealed that they
      possessed a tetranuclear double half-cubane core sandwiched with two trianionic
      ligands from 2,4,6-tris(trifluoromethyl)tetrahydropyran-2,4,6-triol (H3ttpt).
      Complexes [Cu4(ttpt)2(hfac)2(dmf)2.5], [Cu4(ttpt)2(tfa)2(def)4], and
      [Cu4(ttpt)2(hfac)2(H2O)4](fa) were prepared from N,N-dimethylformamide(dmf)-MeOH,
      N,N-diethylformamide (def)-MeOH, and formamide(fa)-MeOH (Htfa=trifluoroacetic
      acid), respectively. A possible mechanism is proposed where a templated aldol
      type reaction takes place between hfac and 1,1,1-trifluoroacetonate. Magnetic
      measurements revealed the presence of antiferromagnetic interaction in the Cu4O6
      core.

PMID- 16981018
TI  - A series of luminescent Cu(I) mixed-ligand complexes containing 2,9-dimethyl-1,10
      phenanthroline and simple diphosphine ligands.
AB  - A series of Cu(I) mixed-ligand complexes containing dmp (2,9-dimethyl-1,10
      phenanthroline) and one of simple diphosphine ligands (Ph2P(CH2)nPPh2) were
      prepared. Among the complexes, [Cu(dppp)(dmp)]PF6 (n=3) and
      [Cu2(dppb)2(dmp)2](PF6)2 (n=4) were characterized by X-ray structure analyses.
      The dppp complex has been characterized as a mononuclear complex, while
      [Cu2(dppb)2(dmp)2]2+ exists as a dinuclear complex in which two dppb ligands
      bridge between the two Cu(I) atoms. Although the distorted tetrahedral structures
      around the central metals of the two complexes are similar, the P-Cu-P angles are
      different between the two complexes. All of the series of complexes show
      photoluminescence in solution, and the intensity of the luminescence increases
      with n (n=2-4). The non-radiative rate constants of the complexes decrease
      markedly with n although radiative rate constants of the complexes are similar.

PMID- 16981019
TI  - The beta-dialdiminato ligand [{N(C6H3Pri(2)-2,6)C(H)}2CPh]-: the conjugate acid
      and Li, Al, Ga and In derivatives.
AB  - The synthesis of the following crystalline complexes is described: [Li(L)(thf)2]
      (), [Li(L)(tmeda)] (), [MCl2(L)] [M=Al (), Ga ()], [In(Cl)(L)(micro
      Cl)2Li(OEt2)2] (), [In(Cl)(L){N(H)C6H3Pri(2)-2,6}] (), [In(L){N(H)C6H3Pri(2)
      2,6}2] (), [{In(Cl)(L)(micro-OH)}2] (), [L(Cl)In-In(Cl)(L)] () (the thf-solvate,
      the solvate-free and the hexane-solvate), [{In(Cl)L}2(micro-S)] () and
      [InCl2(L)(tmeda)] () ([L]-=[{N(C6H3Pri(2)-2,6)C(H)}2CPh]-). From H(L) (), via
      Li(L) in Et2O, and thf, tmeda, AlCl3, GaCl3 or InCl3 there was obtained , , , or
      , respectively in excellent yield. Compound was the precursor for each of , and
      [{InCl3(tmeda)2{micro-(OSnMe2)2}}] () by treatment with one () or two ()
      equivalents of K[N(H)(C6H3Pri(2)-2,6)], successively Li[N(SiMe3)(C6H3Pri(2)-2,6)]
      and moist air (), Na in thf (), tmeda (), or successively tmeda and Me3SnSnMe3
      (). Crystals of (with an equivalent of In) and were obtained from InCl or
      thermolysis of [In(Cl)(L){N(SiMe3)(C6H3Pri(2)-2,6)}] () {prepared in situ from
      and Li[N(SiMe3)(C6H3Pri(2)-2,6)] in Et2O}, respectively. Compound was obtained
      from a thf solution of and sulfur. X-Ray data for crystalline , , , , , and are
      presented. The M(L) moiety in each (not the L-free ) has the monoanionic L
      ligated to the metal in the N,N'-chelating mode. The MN1C1C2C3N2 six-membered
      M(L) ring is pi-delocalised and has the half-chair (, and ) or boat (, and )
      conformation.

PMID- 16981020
TI  - Electrogenerated chemiluminescence of the lithium salts of 8-hydroxyquinoline and
      2-methyl-8-hydroxyquinoline.
AB  - The spectroscopy, electrochemistry, and electrogenerated chemiluminescence (ECL)
      of [(q)(qH)Li]x (qH=8-hydroxyquinolinato) and [(Meq)(MeqH)Li]x (MeQH=2-methyl-8
      hydroxyquinolinato) have been investigated. In both acetonitrile and aqueous
      solutions, [(q)(qH)Li]x and [(Meq)(MeqH)Li]x have absorption maxima at 320 and
      309 nm, respectively. When excited at these wavelengths, the complexes emit
      around 500 nm (blue-green) in acetonitrile. Photoluminescence efficiencies
      (phiem) were 0.036 for [(q)(qH)Li]x and 0.012 for [(Meq)(MeqH)Li]x when compared
      to Ru(bpy)3(2+) (bpy=2,2'-bipyridine) with phiem=0.042. No photoluminescence was
      observed in aqueous media. The complexes show irreversible oxidative
      electrochemistry and quasi-reversible reductions in acetonitrile. ECL
      efficiencies (phiecl) were 0.097 for [(q)(qH)Li]x and 0.080 for [(Meq)(MeqH)Li]x
      when compared to Ru(bpy)(3)2+ (phiecl=1) in aqueous buffered solution and 0.035
      for [(q)(qH)Li]x and 0.028 for [(Meq)(MeqH)Li]x in acetonitrile (0.05 M tri-n
      propylamine (TPrA) as an oxidative-reductive ECL co-reactant). The ECL peaks at a
      potential corresponding to oxidation of both the TPrA and [(q)(qH)Li]x or
      [(Meq)(MeqH)Li]x. Also, qualitative studies using transmission filters suggest
      that both complexes emit ECL in approximately the same blue-green region as their
      photoluminescence, indicating that the same excited state is formed in both
      experiments.

PMID- 16981021
TI  - Group I cation templated formation of luminescent mono- and bis-substituted
      thionaphthol heterobimetallic complexes of Pr, Nd, Eu and Tb.
AB  - Metathesis of lanthanide tris di-tert-butyl beta-diketonates ([Ln(thd)3] Ln=Pr,
      Nd, Eu, Tb) with one or two equivalents of group 1 salts of the sulfur bridged
      binaphtholate dianion [1,1'-S(2-OC10H4But(2)-3,6)2]2-, [M2L], M=K, Li affords
      luminescent mono- and bis-ligand substituted complexes ML[LnL(thd)2].L; M=K,
      Ln=Pr , Nd , Eu and Tb (L=thf, diethyl ether or toluene) and M(thf)2[LnL2(thd)];
      M=Li, Ln=Pr , Nd , Eu , Tb . The potassium salt [K2L] affords mono-L substituted
      complexes most cleanly, while the lithium salt [Li2L] yields the bis-L
      substituted complexes most cleanly. The L ligands function as antenna for the
      sensitised lanthanide-centred emission in Eu3+ and Tb3+ complexes. The X-ray
      single-crystal structures of mono- and bis-L lanthanide complexes of Nd3+ are
      presented.

PMID- 16981022
TI  - Cu2+ and AMP complexation of enlarged tripodal polyamines.
AB  - The synthesis, characterization, Cu2+ coordination and interaction with AMP of
      three tripodal polyamines are reported. The polyamines are based on the structure
      of the tetraamine (tren) which has been enlarged with three propylamino
      functionalities (), with a further anthrylmethyl fragment at one of its terminal
      primary nitrogens () or with naphthylmethyl fragments at its three ends (). The
      protonation constants of all three polyamines show that at pH 6, all six primary
      and secondary nitrogen atoms in the arms are protonated. The interaction with
      Cu2+ and AMP (adenosine-5'-monophosphate) has been studied by potentiometric, UV
      Vis, ESI-MS spectroscopy and NMR techniques. pH-Metric, NMR and ESI/MS techniques
      indicate that and form with AMP adducts of 1:1, 2:1 and 3:1 AMP:L stoichiometries
      in water. This is one of the first examples for the formation of such complexes
      in aqueous solution. Formation of ternary complexes between , , , Cu2+ and AMP is
      observed. Paramagnetic NMR techniques have been used to obtain structural
      information on the binding mode of AMP to the Cu2+- binuclear complexes.

PMID- 16981023
TI  - Synthesis, electrochemical and photophysical properties of phthalocyaninato
      oxotitanium(IV) complexes tetra-substituted at the alpha and beta positions with
      arylthio groups.
AB  - The synthesis, electrochemical and photophysical properties of the following
      tetra-substituted thiol oxotitanium phthalocyanines are reported for the first
      time: 1,(4)-(tetraphenylthiophthalocyaninato)titanium(IV)oxide (); 1,(4)
      (tetrabenzylthiophthalocyaninato)titanium(IV)oxide (); 2,(3)
      (tetraphenylthiophthalocyaninato)titanium(IV)oxide () and 2,(3)
      (benzylthiophthalocyaninato)titanium(IV)oxide (). Cyclic voltammograms of all
      four complexes are similar, with three reversible reduction couples each
      involving a one electron transfer process. The first two reductions were
      confirmed by spectroelectrochemistry to be metal-based reductions due to TiIVPc
      2/TiIIIPc-2 and TiIIIPc-2/TiIIPc-2 redox processes, while the last reduction was
      confirmed to be a ring-based reduction due to TiIIPc-2/TiIIPc-3. Low fluorescence
      quantum yields (0.05-0.14), relatively long triplet lifetimes (150-210 micros)
      and triplet yields (0.31 to 0.82) were observed.

PMID- 16981024
TI  - Hydrido and chloro gallium and aluminium complexes with the tridentate bis(2
      dimethylaminoethyl)amide ligand.
AB  - Five-coordinate gallium and aluminium dihydrides, H2Ga[N(CH2CH2NMe2)2] () and
      H2Al[N(CH2CH2NMe2)2] (), were synthesized and found to be volatile and thermally
      stable. and reacted with H3Ga(NMe3) and H3Al(NMe3), respectively, to form
      H2Ga[N(CH2CH2NMe2)2]GaH3 () and H2Al[N(CH2CH2NMe2)2]AlH3 (), in which the amido
      nitrogen bridged between the MH2 and MH3 groups (M=Ga or Al). A mixed metal
      complex, H2Al[N(CH2CH2NMe2)2]GaH3 () was obtained from the reaction of with
      H3Al(NMe3) or with H3Ga(NMe3), and a crystal consisting of a mixture of and was
      structurally characterized. The five-coordinate chloro derivative,
      Cl2Ga[N(CH2CH2NMe2)2] (), was synthesized and characterized.

PMID- 16981025
TI  - The N-alkyldithiocarbamato complexes [M(S2CNHR)2] (M=Cd(II) Zn(II); R=C2H5, C4H9,
      C6H13, C12H25); their synthesis, thermal decomposition and use to prepare of
      nanoparticles and nanorods of CdS.
AB  - A series of N-alkyldithiocarbamato complexes [M(S2CNHR)2] (M=Cd(II), Zn(II);
      R=C2H5, C4H9, C6H13, C12H25) have been synthesised and characterized. The
      decomposition of these complexes to sulfates has been investigated, and a
      mechanism proposed. The structures of [Zn(S2CNHHex)2], [Cd(SO4)2(NC5H5)4)]n and
      [Cd(SO4)2(NC5H5)2(H2O)2)]n have been determined by X-ray single crystal method.
      The cadmium complex [Cd(S2CNHC12H25)2] and zinc complex [Zn(S2CNHC6H13)2] were
      used as single-source precursors to synthesize CdS and ZnS nanoparticles,
      respectively. The synthesis of CdS nanoparticles was carried under various
      thermolysis conditions and changes in the shape of derived nanoparticles were
      studied by transmission electron microscope (TEM).

PMID- 16981026
TI  - Synthesis, structural characterization, and properties of chromium(III) complexes
      containing amidinato ligands and eta2-pyrazolato, eta(2)-1,2,4-triazolato, or
      eta1-tetrazolato ligands.
AB  - Treatment of anhydrous chromium(III) chloride with 2 or 3 equivalents of 1,3-di
      tert-butylacetamidinatolithium or 1,3-diisopropylacetamidinatolithium in
      tetrahydrofuran at ambient temperature afforded Cr(tBuNC(CH3)NtBu)2(Cl)(THF) and
      Cr(iPrNC(CH3)NiPr)3 in 78% and 65% yields, respectively. Treatment of
      Cr(tBuNC(CH3)NtBu)2(Cl)(THF) with the potassium salts derived from pyrazoles and
      1,2,4-triazoles afforded Cr(tBuNC(CH3)NtBu)2(X), where X=3,5-disubstituted
      pyrazolato or 3,5-disubstituted 1,2,4-triazolato ligands, in 65-70% yields. X-Ray
      crystal structure analyses of Cr(tBuNC(CH3)NtBu)2(Me2pz) (Me2pz=3,5
      dimethylpyrazolato) and Cr(tBuNC(CH3)NtBu)2(Me2trz) (Me2trz=3,5-dimethyl-1,2,4
      triazolato) revealed eta2-coordination of the Me2pz and Me2trz ligands. Treatment
      of Cr(tBuNC(CH3)NtBu)2(Cl)(THF) with trifluoromethyltetrazolatosodium (NaCF3tetz)
      in the presence of 4-tert-butylpyridine afforded Cr(tBuNC(CH3)NtBu)2(CF3tetz)(4
      tBupy) in 30% yield. An X-ray crystal structure determination showed eta1
      coordination of the tetrazolato ligand through the 2-nitrogen atom. The complexes
      Cr(iPrNC(CH3)NiPr)3 and Cr(tBuNC(CH3)NtBu)2(X) are volatile and sublime with <1%
      residue between 120 and 165 degrees C at 0.05 Torr. In addition, these complexes
      are thermally stable at >300 degrees C under an inert atmosphere such as nitrogen
      or argon. Due to the good volatility and high thermal stability, these new
      compounds are promising precursors for the growth of chromium-containing thin
      films using atomic layer deposition.

PMID- 16981027
TI  - [Standardization of the terminology of the academic medical centers and
      biomedical research centers, in the English language, for journal article
      sending].
AB  - PURPOSE: To suggest a standardization, in the English language, the formatting of
      the citation of the research centers. METHODS: From three more recent
      publications of the first 20 journals available in Brazilian Portal of Scientific
      Information - Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
      (CAPES), with bigger factor of impact during the year of 2004, according of
      information in ISI Web of Knowledge Journal Citation Reports database in biennium
      2004-2005, had extracted the formats of citations of the research centers. An
      analogy to the institutional hierarchie step of the Federal University of Sao
      Paulo (UNIFESP) was carried out, and the formats most frequent, in the English
      language, had been adopted as standard to be suggested to cite the research
      centers for sending articles. RESULTS: In relation to the citation
      "Departamento", was standardized "Department of ..." (being "..." the name in
      English of the Department), to the citation "Programa de Pos-Graduacao" "...
      Program", "Disciplina" "Division of ...", "Orgaos, Grupos e Associacoes" "...
      Group ", "Setor" "Section of...", "Centro" "Center for ...", "Unidade" "... Unit
      ", "Instituto" "Institute of ...", "Laboratorio" "Laboratory of ..." and "Grupo"
      "Group of ...".

PMID- 16981028
TI  - Feasibility analysis of loop colostomy closure in patients under local
      anesthesia.
AB  - PURPOSE: To verify prospectively the practicability of performing loop colostomy
      closure under local anesthesia and sedation. METHODS: In this study, 21 patients
      underwent this operation. Lidocaine 2% and bupivacaine 0.5% were utilized. Pain
      was evaluated during the operation, on the first postoperative day and at
      hospital discharge. Intraoperative events, postoperative complications and the
      acceptability of this procedure were analyzed. RESULTS: The mean duration of the
      operation was 133 minutes (range: 85 to 290 minutes). The mean postoperative
      hospitalization was four days (range: one to twelve days). No patients died.
      Complications occurred in two patients (9.4%): abdominal wall hematoma and
      operative wound infection. With regard to pain severity, scores of less than or
      equal to three were indicated in the intraoperative evaluation by 80% of the
      patients (17/21) and on the first postoperative day by 85% (18/21). At hospital
      discharge, 95.2% of the patients (20/21) said they were in favor of the local
      anesthesia technique. CONCLUSION: Loop colostomy closure under local anesthesia
      and sedation is feasible, safe and acceptable to patients.

PMID- 16981030
TI  - Nitric oxide monocyte production levels in patients with the hepatosplenic form
      of schistosomiasis mansoni who underwent splenectomy, ligature of the left
      gastric vein and auto implantation of spleen tissue in the major omentum.
AB  - PURPOSE: To measure the levels of NO production by monocytes in patients with the
      hepatosplenic form of Schistosomiasis mansoni who underwent splenectomy, ligature
      of the left gastric vein and auto implantation of spleen tissue in the major
      omentum. METHODS: Four groups of volunteers were enrolled in the investigation:
      G1 - 12 patients with S. mansoni infection in its hepatosplenic form without any
      kind of treatment (SMH); G2 - 13 SMH patients who underwent medical treatment and
      portal hypertension decompression splenectomy and ligature of the left gastric
      vein (SMH/SLGV); G3 - 19 patients similar to the later group, but additionally
      received auto implantation of spleen morsels in the major omentum (SMH/SLGV/AI);
      and G4 - 15 individuals with no S. mansoni infection coming from the same
      geographical area and presenting similar socio-economical status (CG). Nitrite
      production by monocytes was determined by a standard Griess reaction adapted to
      microplates. The results were presented by mean +/- SD for each group.
      Significant differences in NO production by monocytes were determined by Tukey
      Kramer multicomparisons test. Probability values of 0.05 were considered
      significant. RESULTS: Patients from G1 (SMH) showed lower level of NO production
      by monocytes (5.28 +/- 1.28 micromol/ml). Patients from G2 (SMH/SLGV) showed
      similar results (6.67 +/- 0.44 micromol/ml-q = 2.681 p > 0.05). Individuals of G4
      (CG) showed higher level of NO production by monocytes (8.19 +/- 2.74
      micromol/ml). Patients from G3 (SMH/SGLV/AI) showed similar NO production by PBMC
      as compared to individuals of G4 (CG) - (7.41 +/- 1.65 micromol/ml- q = 1.615 p >
      0.05). The volunteers from G4 (CG) and G3 (SMH/SLGV/AI) showed significantly
      greater levels of NO production by monocytes as compared to those from G1 (SMH) -
      (q = 5.837 p < 0.01, and q = 4.285 p < 0.05). CONCLUSION: Collectively, the
      results point to a restoration of NO normal production by monocytes in SHM
      patients who underwent medical and surgical treatments, especially in those who
      had received auto implantation of spleen tissue in the major omentum after
      splenectomy and ligature of the left gastric vein. The data gives further support
      to the hypothesis that this additional procedure is important in the restoration
      of the immune response of these patients, since NO synthesis by the monocytes
      correlates with protective immunity against infection; thus, protecting them
      against overwhelming post splenectomy infection.

PMID- 16981029
TI  - Experimental model in the qualitative and quantitative assessment of non
      Helicobacter gastric microflora under proton pump inhibitors action.
AB  - PURPOSE: To evaluate models of gastric material collection from Wistar rats with
      and without using proton pump inhibitors(PPIs). METHODS: Twenty-four rats
      underwent intraperitoneal omeprazol treatment, and other 12 received similar
      treatment with 0.9% saline. All animals underwent collection of gastric material
      samples, after stomach removal, by either biopsies, or aspirates, or swabs.
      Samples were bacteriologically processed in order to identify species and
      strains. Values are described as natural logarithm of colony former units per mL
      [Ln(CFU/mL)]. Kruskal-Wallis and Mann-Whitney non-parametric tests were used, and
      p<0.05 was set as statistically significant. RESULTS: Significant difference was
      not seen for Ln (UFC/mL) values among the three methods of collection
      irrespective of using or not omeprazol. Also, significant difference was not seen
      in Ln (UFC/mL) values when comparing a method with each others, either using
      omeprazol or placebo. A significant increase of bacteria strains occurred when
      PPI was used, and this was seen on the three ways of collection, mainly in biopsy
      and swab. CONCLUSION: No difference occurred among the three methods of
      collecting bacteria samples from stomachs of rats, either when using placebo or
      omeprazol. A remarkable change is seen on animals bacterial microflora when PPIs
      are used, and bacteria are better identified when swab and biopsy are used.

PMID- 16981032
TI  - Veress needle insertion in the left hypochondrium in creation of the
      pneumoperitoneum.
AB  - PURPOSE: To test the efficacy of the puncture in the left hypochondrium as an
      alternative method. METHODS: Sixty-two patients randomly distributed into two
      groups were studied: Group LH, puncture in the left hypochondrium (n=30), and
      Group ML, puncture in the abdominal midline (n=32). The following were assessed:
      needle positioning tests, number of failed attempts at needle insertion, and time
      needed for creation of pneumoperitoneum. Gas flow, volume and intraperitoneal
      pressure were recorded at every 20 seconds, until a 12 mmHg pressure was reached
      inside the peritoneal cavity. RESULTS: A similar number of positive results for
      the needle positioning tests were observed in both groups. Two failed attempts to
      reach the peritoneal cavity were observed in Group ML and one in Group LH. The
      time necessary for the creation of pneumoperitoneum was on average 3 minutes and
      46 seconds for Group LH, and 4 minutes and 2 seconds for Group ML. Average gas
      flow, volume and pressure were equivalent for both groups. CONCLUSION: Puncture
      in the left hypochondrium was as effective as puncture in the abdominal midline
      for the creation of pneumoperitoneum.

PMID- 16981033
TI  - Parametric evaluation of methotrimeprazine-midazolam-ketamine and
      methotrimeprazine-midazolam-ketamine-xylazine combination in dogs.
AB  - PURPOSE: To evaluate the parameters of dogs anesthetized by different
      dissociative drugs protocols through continuous intravenous infusion. METHODS:
      Thirty healthy dogs of both sexes were assigned randomly to three groups (G1, G2,
      and G3). G1 was administered with methotrimeprazine as a pre-anesthetic
      medication, intravenously midazolam-ketamine as bolus for induction and midazolam
      ketamine by continuous intravenous infusion for a 60 minute-period of
      maintenance. G2: the same as for G1. plus an increase in the midazolam dose
      during maintenance. G3: the same treatment as for G2, plus the addition of
      xylazine during maintenance. Immediately after induction the anesthetic
      maintenance started, and measures were taken 15 minutes after pre-medication, at
      10 minutes intervals, during maintenance (M0 to M7). RESULTS: Bradycardia,
      atrioventricular blockage, bradypnea and hypoxemia were shown in G3. G1 and G2
      showed a slight hypotension only. CONCLUSION: There were some advantages by using
      the continuous intravenous via: no parameters oscillation and reduction in the
      anesthetic recovery period. The increase in midazolam dose brought about little
      parametric variations which were greater when xylazine was used, with a
      consequent hypoxemia, bradyarrhytmia, and decrease in respiratory frequency and
      minute volume.

PMID- 16981034
TI  - The role of biological adhesive and suture material on rabbit hepatic injury.
AB  - PURPOSE: To evaluate the performance of fibrin adhesive and absorbable suture
      thread in the repairing of hepatic injures in rabbits. METHODS: New Zealand
      albino rabbits (n=16), males and females, from 5 to 6 months old, average weight
      of 2500 g, were distributed randomly in Group A (n-8) - biological adhesive and
      Group B (n=8) - suture thread. After anesthesia with acepromazine (1mg/Kg),
      ketamine (50mg/Kg) and fentanyl EV (0,5ml/Kg), it was performed a supra-umbilical
      median laparotomy, the median hepatic lobe was isolated and subjected to severe
      standardized incision. In the group B the incision edges were sutured with simple
      4-0 catgut, in separated stitches. It was evaluated the total time of the
      procedure, the hemostasis time and hemorrhage volume. In the 21st post-operative
      day it was evaluated the presence of adherences and signs of infection in the
      abdominal cavity, and it was followed by the resection of the median hepatic lobe
      for the histological evaluation. RESULTS: The calculated mean and standard
      deviation showed that the procedure time, hemostasis time and bleeding amount
      were significantly smaller in the group of animals subjected to the use of fibrin
      adhesive. The surgical abdominal incision was significantly more extensive in the
      animals of the suture group (average of 6,8 cm) in relation to the adhesive group
      (average of 3,8), as well as the number of occurrences of abscesses. The
      adherence of the intestinal ansas to the sutured incision (group B) occurred in
      five cases and the major omentum adhesion occurred in all animals. In the group A
      (adhesive) it occurred adherences of the major omentum in three cases. The
      microscopy of the hepatic incision repaired with the use of fibrin showed that
      the inflammatory infection is less intense, not associated with the formulation
      of secretion in the abscesses, and therefore has a more favorable later
      cicatricial aspect than a conventional suture with surgical thread. CONCLUSION:
      In agreement with other biomedical literature works, the fibrin adhesive is a
      viable option for the performance of hemostasis in a animal model (rabbit) with
      severe hepatic injury.

PMID- 16981035
TI  - Effect of soluble fiber or fructooligosaccharide supplementation upon
      trinitrobenzenesulphonic acid induced colitis in rats.
AB  - PURPOSE: To evaluate the effect of soluble fiber or fructooligosaccharide (FOS)
      supplementation upon trinitrobenzene sulphonic acid (TNBS)-induced colitis in
      rats. METHODS: 64 Wistar rats were given water, soluble fiber or FOS
      intragastrically during 14 days prior to colitis induction with TNBS (n=48) or
      rectal enema with water (n=16; control group). On the 7th or 14th day following
      colitis induction the rats were weighed and euthanized in order to determine the
      colon weight/length ratio and macroscopic and microscopic scores. RESULTS: On the
      7th day following colitis induction the body weight had decreased significantly,
      the colon weight/length ratio had increased and macroscopic and microscopic colon
      lesions were observed. On the 14th day following colitis induction no difference
      in body weight was observed, in spite of the persistence of macroscopic and
      microscopic lesions and increased colon weight/length ratio. Supplementation with
      soluble fiber or FOS did not revert colon lesions or any of the study parameters.
      Supplementation with FOS, but not with fiber, was associated with increased colon
      weight/length ratio on the 14th day. CONCLUSION: Supplementation with soluble
      fiber or FOS produced no significant impact on TNBS-induced colitis in rats.

PMID- 16981036
TI  - Subtotal splenectomy preserving the lower pole in rats: technical, morphological
      and functional aspects.
AB  - PURPOSE: To assess the possibility of preserving the lower pole of the spleen,
      supplied by the inferior lobar vessels and segmental vessels, or by vessels of
      the gastrosplenic ligament, in subtotal splenectomy; to study the viability and
      function of the lower pole of the spleen. METHODS: Thirty-six male Wistar rats
      were used in this study. Said animals weighed 273-390 g ( 355.2 +/- 30.5 g ), and
      were randomly distributed into three groups. Group 1 comprised ten animals which
      were submitted to exploratory laparotomy with spleen manipulation (sham
      operation). Group 2 comprised 16 animals which were submitted to total
      splenectomy. Group 3 comprised ten animals which were submitted to subtotal
      splenectomy, preserving the lower pole of the spleen. Blood was collected from
      all animals before and 90 days after surgery to measure the levels of cholesterol
      and triglycerides. The animals were sacrificed 90 days after surgery. Spleens and
      remaining spleens were removed for macroscopic and microscopic examination.
      RESULTS: Surgery was performed with no complications in all groups. Six animals
      died in group 2. Spleens of groups 1 and 2, and lower poles of group 3 were
      macroscopically viable. Apparent white pulp hyperplasia was observed in group 1.
      In group 3, slight inflammation and capsular fibrosis were observed at the
      incision site, as well as diffuse hemosiderosis in the red pulp. Average mass of
      remaining spleen was 35.84% +/- 4.31%. No significant difference was observed
      between preoperative and late postoperative lipid levels in groups 1 and 3 (p >
      0.05). Late postoperative lipid levels significantly increased in group 2.
      CONCLUSIONS: Preservation of the lower pole of the spleen (supplied by
      gastrosplenic vessels or inferior lobar vessels and segmental vessels) was
      possible with subtotal splenectomy. The lower pole was macroscopically and
      microscopically viable in all cases. Subtotal splenectomy preserving the lower
      pole prevented changes in lipid levels, which were observed in rats submitted to
      total splenectomy. Plasma lipid levels in rats submitted to subtotal splenectomy
      were similar to those observed in sham operated rats.

PMID- 16981037
TI  - The role of bovine preserved peritoneum in rats ventral hernia: a histological
      evaluation.
AB  - PURPOSE: To assess the role of preserved bovine parietal peritoneum as a material
      for hernia repair in a rat ventral hernia model. METHODS: An abdominal wall
      defect (15mm x 25mm) was created in Wistar male rats (n=40). Control animals
      (n=20) had the polypropylene (PP) mesh sutured into the defect, whereas bovine
      preserved peritoneum (BPP) was used in experimental group (n=20). After 7 and 28
      days, the abdominal wall was taken off and histological studies of the amount of
      collagen by Sirius Red stain and morphometric evaluation consisted in
      quantitative analysis of the collagen by using specific software (Imagelab). The
      Mann-Whitney, Kruskal-Wallis and ANOVA tests were applied for statistical
      analysis (pd"0.05). RESULTS: Histological examination revealed no difference
      between the BPP and PP groups (p = 0.55 NS). CONCLUSION: BPP is suitable for the
      closure of ventral hernias in rat model as shown by its morphological properties.

PMID- 16981038
TI  - Morphological analysis of three wound-cleaning processes on potentially
      contamined wounds in rats.
AB  - PURPOSE: To evaluate the inflammatory response of potentially infected wounds
      treated with isotonic saline solution, chlorhexidine and PVP-I, seven days after
      surgery. METHODS: Thirty-two male rats were used, divided into 4 groups. All
      animals had their surgical wounds infected with a standard bacterial inoculum.
      Control group (A): animals had their surgical wounds sutured without any kind of
      cleaning. Saline solution group (B): animals had their wounds cleaned with saline
      solution. Chlorhexidine group (C): animals had their wounds cleaned with
      chlorhexidine. PVP-I group (D): animals had their wounds cleaned with PVP-I.
      Seven days after surgery, all the animals had their skin submitted to microscopic
      and macroscopic evaluation. RESULTS: Edema was found on all histological slices
      analyzed, as well as vascular proliferation and congestion. Groups A and D showed
      presence of mild neutrophilic infiltrate, and moderate lymphocytic and macrophage
      infiltrate. Group B showed severe neutrophilic, macrophage, and lymphocytic
      infiltrate. Group C showed moderate neutrophilic, macrophage, and lymphocytic
      infiltrate. CONCLUSION: Group D was the group which showed inflammatory
      infiltrate most similar to the group that was not submitted to treatment.

PMID- 16981039
TI  - Morphology of autogenous bone graft and castor oil polyurethane in the
      infraorbital rim of rabbits: a comparative study.
AB  - PURPOSE: Morphological study comparing castor oil polyurethane and autogenous
      bone graft to repair bone defect in zygomatic bone of rabbits. METHODS: Twenty
      four adult, male New Zealand rabbits were randomly distributed between two groups
      of twelve. Bone defects of 5mm in diameter were cut through the zygomatic bone
      and filled with polyurethane discs in the experimental group or autogenous bone
      harvested from the tibia in the control group. Animals were sacrificed after 30,
      60 or 90 days, and the zygomatic bones were macro- and microscopically analyzed.
      Student's, Fisher's, chi-squared and McNemar's tests were used for statistical
      analysis. RESULTS: Both the castor oil polyurethane and the autograft adapted
      well to the defect, with no need for fixation. Fibrous connective tissue
      encapsulated the polyurethane, but no inflammation or giant cell reaction was
      observed. Acidophilic and basophilic areas were observed inside the micropores of
      the polyurethane, suggesting cell nuclei. After 90 days, bone repair with a
      lamellar pattern of organization was observed in the control group. CONCLUSION:
      The castor oil polyurethane was biocompatible and did not cause inflammation. It
      may be considered an alternative to fill bone defects.

PMID- 16981040
TI  - Effects of structural injure in the bile bacterial contamination after balloon
      transduodenal sphincteroplasty (papillary dilation) in dogs.
AB  - PURPOSE: To evaluate, in dogs, the biliary sphincter subjected to dilation by
      hydrostatic balloon by the point of view of structural alterations of the papilla
      and the biochemestry and bacterial contamination of the bile. METHODS: Twenty
      dogs were submitted to laparotomy, duodenotomy, and enlargement of the major
      duodenal papilla- GA(n=10) - with balloon of 8mm inflated with pressure of 0,5
      atm, during 2 minutes or to the sham procedure - GB(n=10). Blood samples
      collected on times t(0 day), t(7 days) and t(28 days) were subjected to dosages
      of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) for cholestasis
      evaluation. The collected material from the gall bladder at the same times were
      registered and numbered to be submitted to culture in BHI, blood agar (rich, non
      selective element) and Mac Conkey (selective element for Gram-negative bacillus.
      On the 28th day three fragments of the papilla were tranversally cut by the
      choledoc axis 3mm from the duodenal papilla and the cuts, stained with
      hematoxylin-eosin and Masson's tricome, were evaluated according to their
      inflammatory reaction. RESULTS: The GGT and ALP averages on the three periods in
      the groups A and B did not show significant differences, not being characterizes
      the cholestasis. The bacterian contamination was significantly higher in GA
      (2,19) than in GB (1,96); the contamination was lower in the initial time
      compared with 7 and 28 days (t0<t7 and t 28) in GA and GB (t0<t 28). The chronic
      inflammatory alteration of the mucosa occurred in 60% of the GA animals and in
      80% of the GB animals. There was not mural inflammation. CONCLUSION: The duodenal
      papilla dilation or its simple manipulation leads to the bacterial contamination
      of the gall bladder, not associated with cholestasis. The morphologic lesions are
      more intense in the late phase, not associated with an eventual papilla
      esthenosis.

PMID- 16981041
TI  - Hemorrhoids: an experimental model in monkeys.
AB  - PURPOSE: Hemorrhoids are a matter of concern due to a painful outcome. We
      describe a simple, easy and reliable experimental model to produce hemorrhoids in
      monkeys. METHODS: 14 monkeys (Cebus apella) were used. After general anesthesia,
      hemorrhoids were induced by ligation of the inferior hemorrhoidal vein, which is
      very alike to humans. The vein was located through a perianal incision, dissected
      and ligated with a 3-0 vicryl. The skin was sutured with a 4-0 catgut thread.
      Animals were kept in appropriate cages and evaluated daily. RESULTS: Nine days
      later there were hemorrhoidal piles in the anus in fifty percent (50%) of the
      animals. Outcome was unremarkable. There was no bleeding and all animals showed
      no signs of pain or suffering. CONCLUSION: This is an affordable and reliable
      experimental model to induce hemorrhoids for experimental studies.

PMID- 16981042
TI  - Profile of the Brazilian scientific production in multiple sclerosis.
AB  - This paper analyzes the profile of the Brazilian output in the field of multiple
      sclerosis from 1981 to 2004. The search was conducted through the MEDLINE and
      LILACS databases, selecting papers in which the term "multiple sclerosis" was
      defined as the main topic and "Brazil" or "Brasil" as others. The data were
      analyzed regarding the themes, the state in Brazil and institution where the
      papers were produced, the journals where the papers were published, journal's
      impact factor, and language. The search disclosed 141 documents (91 from MEDLINE
      and LILACS, and 50 from LILACS only) published in 44 different journals (23 of
      them MEDLINE-indexed). A total of 111 documents were produced by 17 public
      universities, 29 by 3 private medical schools and 1 by a non-governmental
      organization. There were 65 original contributions, 37 case reports, 20 reviews,
      6 PhD dissertations, 5 guidelines, 2 validation studies, 2 clinical trials, 2
      chapters in textbooks, 1 Master of Science thesis, and 1 patient education
      handout. The journal impact factor ranged from 0.0217 to 6.039 (median 3.03). Of
      91 papers from MEDLINE, 65 were published by Arquivos de Neuro-Psiquiatria. More
      than 90% of the papers were written in Portuguese. Sao Paulo was the most
      productive state in the country, followed by Rio de Janeiro, Minas Gerais and
      Parana. Eighty-two percent of the Brazilian output came from the Southeastern
      region.

PMID- 16981043
TI  - Nucleotide-sugar transporters: structure, function and roles in vivo.
AB  - The glycosylation of glycoconjugates and the biosynthesis of polysaccharides
      depend on nucleotide-sugars which are the substrates for glycosyltransferases. A
      large proportion of these enzymes are located within the lumen of the Golgi
      apparatus as well as the endoplasmic reticulum, while many of the nucleotide
      sugars are synthesized in the cytosol. Thus, nucleotide-sugars are translocated
      from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum by
      multiple spanning domain proteins known as nucleotide-sugar transporters (NSTs).
      These proteins were first identified biochemically and some of them were cloned
      by complementation of mutants. Genome and expressed sequence tag sequencing
      allowed the identification of a number of sequences that may encode for NSTs in
      different organisms. The functional characterization of some of these genes has
      shown that some of them can be highly specific in their substrate specificity
      while others can utilize up to three different nucleotide-sugars containing the
      same nucleotide. Mutations in genes encoding for NSTs can lead to changes in
      development in Drosophila melanogaster or Caenorhabditis elegans, as well as
      alterations in the infectivity of Leishmania donovani. In humans, the mutation of
      a GDP-fucose transporter is responsible for an impaired immune response as well
      as retarded growth. These results suggest that, even though there appear to be a
      fair number of genes encoding for NSTs, they are not functionally redundant and
      seem to play specific roles in glycosylation.

PMID- 16981044
TI  - Partial purification of tightly bound mitochondrial hexokinase from maize (Zea
      mays L.) root membranes.
AB  - In mammals, hexokinase (HK) is strategically located at the outer membrane of
      mitochondria bound to the porin protein. The mitochondrial HK is a crucial
      modulator of apoptosis and reactive oxygen species generation. In plants, these
      properties related to HK are unknown. In order to better understand the
      physiological role of non-cytosolic hexokinase (NC-HK) in plants, we developed a
      purification strategy here described. Crude extract of 400 g of maize roots (230
      mg protein) contained a specific activity of 0.042 micromol G6P min(-1) mg PTN(
      1). After solubilization with detergent two fractions were obtained by DEAE
      column chromatography, NC-HK 1 (specific activity = 3.6 micromol G6P min(-1) mg
      PTN(-1) and protein recovered = 0.7 mg) and NC-HK 2. A major purification (yield
      = 500-fold) was obtained after passage of NC-HK 1 through the hydrophobic phenyl
      Sepharose column. The total amount of protein and activity recovered were 0.04
      and 18%, respectively. The NC-HK 1 binds to the hydrophobic phenyl-Sepharose
      matrix, as observed for rat brain HK. Mild chymotrypsin digestion did not affect
      adsorption of NC-HK 1 to the hydrophobic column as it does for rat HK I. In
      contrast to mammal mitochondrial HK, glucose-6-phosphate, clotrimazole or
      thiopental did not dissociate NC-HK from maize (Zea mays) or rice (Oryza sativa)
      mitochondrial membranes. These data show that the interaction between maize or
      rice NC-HK to mitochondria differs from that reported in mammals, where the
      mitochondrial enzyme can be displaced by modulators or pharmacological agents
      known to interfere with the enzyme binding properties with the mitochondrial
      porin protein.

PMID- 16981045
TI  - High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients.
AB  - Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an
      autosomal recessive mode of inheritance. It is a paradigm for therapeutic
      intervention in medical genetics due to the existence of effective enzyme
      replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian
      patients, carried out in order to establish the frequency of the most common
      mutations and to provide prognostic information based on genotype-phenotype
      correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of
      all the alleles, but N370S/N370S homozygosity was found in only 10% of the
      patients, a much lower frequency than expected, suggesting that most individuals
      presenting this genotype may not receive medical attention. Recombinant alleles
      were detected at a high frequency: 44% of the chromosomes bearing mutation L444P
      had other mutations derived from the pseudogene sequence, present in 25% of
      patients. Three neuronopathic type 2 patients were homozygous for L444P, all
      presenting additional mutations (E326K or recombinant alleles) that probably lead
      to the more severe phenotypes. Six children, classified as type 1 GD patients,
      had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest
      later in life. This would indicate the need for a higher treatment dose during
      enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous
      type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients.
      These findings indicate that G377S cannot be unambiguously classified as mild and
      suggest an allele-dose effect for this mutation.

PMID- 16981046
TI  - The blockade of cyclooxygenases-1 and -2 reduces the effects of hypoxia on
      endothelial cells.
AB  - Hypoxia activates endothelial cells by the action of reactive oxygen species
      generated in part by cyclooxygenases (COX) production enhancing leukocyte
      transmigration. We investigated the effect of specific COX inhibition on the
      function of endothelial cells exposed to hypoxia. Mouse immortalized endothelial
      cells were subjected to 30 min of oxygen deprivation by gas exchange. Acridine
      orange/ethidium bromide dyes and lactate dehydrogenase activity were used to
      monitor cell viability. The mRNA of COX-1 and -2 was amplified and semi
      quantified before and after hypoxia in cells treated or not with indomethacin, a
      non-selective COX inhibitor. Expression of RANTES (regulated upon activation,
      normal T cell expressed and secreted) protein and the protective role of heme
      oxygenase-1 (HO-1) were also investigated by PCR. Gas exchange decreased partial
      oxygen pressure (PaO2) by 45.12 +/- 5.85% (from 162 +/- 10 to 73 +/- 7.4 mmHg).
      Thirty minutes of hypoxia decreased cell viability and enhanced lactate
      dehydrogenase levels compared to control (73.1 +/- 2.7 vs 91.2 +/- 0.9%, P <
      0.02; 35.96 +/- 11.64 vs 22.19 +/- 9.65%, P = 0.002, respectively). COX-2 and HO
      1 mRNA were up-regulated after hypoxia. Indomethacin (300 microM) decreased COX
      2, HO-1, hypoxia-inducible factor-1alpha and RANTES mRNA and increased cell
      viability after hypoxia. We conclude that blockade of COX up-regulation can
      ameliorate endothelial injury, resulting in reduced production of chemokines.

PMID- 16981047
TI  - Mechanisms underlying gas exchange alterations in an experimental model of
      pulmonary embolism.
AB  - The aim of the present study was to determine the ventilation/perfusion ratio
      that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and
      volumetric capnography in a model of experimental acute pulmonary embolism.
      Pulmonary embolization with autologous blood clots was induced in seven pigs
      weighing 24.00 +/- 0.6 kg, anesthetized and mechanically ventilated. Significant
      changes occurred from baseline to 20 min after embolization, such as reduction in
      oxygen partial pressures in arterial blood (from 87.71 +/- 8.64 to 39.14 +/- 6.77
      mmHg) and alveolar air (from 92.97 +/- 2.14 to 63.91 +/- 8.27 mmHg). The
      effective alveolar ventilation exhibited a significant reduction (from 199.62 +/-
      42.01 to 84.34 +/- 44.13) consistent with the fall in alveolar gas volume that
      effectively participated in gas exchange. The relation between the alveolar
      ventilation that effectively participated in gas exchange and cardiac output (V
      Aeff/Q ratio) also presented a significant reduction after embolization (from
      0.96 +/- 0.34 to 0.33 +/- 0.17 fraction). The carbon dioxide partial pressure
      increased significantly in arterial blood (from 37.51 +/- 1.71 to 60.76 +/- 6.62
      mmHg), but decreased significantly in exhaled air at the end of the respiratory
      cycle (from 35.57 +/- 1.22 to 23.15 +/- 8.24 mmHg). Exhaled air at the end of the
      respiratory cycle returned to baseline values 40 min after embolism. The arterial
      to alveolar carbon dioxide gradient increased significantly (from 1.94 +/- 1.36
      to 37.61 +/- 12.79 mmHg), as also did the calculated alveolar (from 56.38 +/-
      22.47 to 178.09 +/- 37.46 mL) and physiological (from 0.37 +/- 0.05 to 0.75 +/-
      0.10 fraction) dead spaces. Based on our data, we conclude that the severe
      arterial hypoxemia observed in this experimental model may be attributed to the
      reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q
      progressively improves after embolization, a fact attributed to the alveolar
      ventilation redistribution induced by hypocapnic bronchoconstriction.

PMID- 16981048
TI  - Systemic and regional hemodynamic effects of enalaprilat infusion in experimental
      normotensive sepsis.
AB  - Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic
      perfusion in distinct shock states. We hypothesized that enalaprilat potentiates
      the benefits of early fluid resuscitation in severe experimental sepsis,
      particularly in the splanchnic region. Anesthetized and mechanically ventilated
      mongrel dogs received an intravenous infusion of live Escherichia coli over a
      period of 30 min. Thereafter, two interventions were performed: fluid infusion
      (normal saline, 32 mL/kg over 30 min) and enalaprilat infusion (0.02 mg kg(-1)
      min(-1) for 60 min) in randomized groups. The following groups were studied:
      controls (fluid infusion, N = 4), E1 (enalaprilat infusion followed by fluid
      infusion, N = 5) and E2 (fluid infusion followed by enalaprilat infusion, N = 5).
      All animals were observed for a 120 min after bacterial infusion. Mean arterial
      pressure, cardiac output (CO), portal vein blood flow (PVBF), systemic and
      regional oxygen-derived variables, and lactate levels were measured. Rapid and
      progressive reductions in CO and PVBF were induced by the infusion of live
      bacteria, while minor changes were observed in mean arterial pressure. Systemic
      and regional territories showed a significant increase in oxygen extraction and
      lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were
      also detected. Fluid replacement promoted transient benefits in CO and PVBF.
      Enalaprilat after fluid resuscitation did not affect systemic or regional
      hemodynamic variables. We conclude that in this model of normotensive sepsis
      inhibition of angiotensin-converting enzyme did not interfere with the course of
      systemic or regional hemodynamic and oxygen-derived variables.

PMID- 16981049
TI  - Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH.
AB  - Glucocorticoids (Gc) influence the differentiation of neural crest-derived cells
      such as those composing sympathoadrenal tumors like pheochromocytomas, as well as
      neuroblastomas and gangliomas. In order to obtain further information on the
      effects of Gc on cells evolving from the neural crest, we have used the human
      neuroblastoma cell line SK-N-SH to analyze: 1) the presence and the binding
      characteristics of Gc receptors in these cells, 2) the effect of dexamethasone
      (Dex) on the migration of SK-N-SH cells, and 3) the effect of Dex on the
      organization of the cytoskeleton of SK-N-SH cells. We show that: 1) receptors
      that bind [(3)H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of
      47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell) are present in
      cytosolic preparations of SK-N-SH cells, and 2) treatment with Dex (in the range
      of 10 nM to 1 microM) has an inhibitory effect (from 100% to 74 and 43%,
      respectively) on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum.
      This inhibition is completely reversed by the Gc receptor antagonist RU486 (1
      microM), and 3) as demonstrated by fluorescent phalloidin-actin detection, the
      effect of Dex (100 nM) on SK-N-SH cell migration is accompanied by modifications
      of the cytoskeleton organization that appear with stress fibers. These
      modifications did not take place in the presence of 1 microM RU486. The present
      data demonstrate for the first time that Dex affects the migration of
      neuroblastoma cells as well as their cytoskeleton organization by interacting
      with specific receptors. These findings provide new insights on the mechanism(s)
      of action of Gc on cells originating in the neural crest.

PMID- 16981050
TI  - Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and
      cyanocobalamin treatment in mandibular molar surgery.
AB  - Third molar extraction is a common procedure frequently accompanied by moderate
      or severe pain, and involves sufficient numbers of patients to make studies
      relatively easy to perform. The aim of the present study was to determine the
      efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg
      dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin)
      when compared with 20 mg piroxicam alone (Feldene) in mandibular third molar
      surgery. Eighty patients scheduled for removal of the third molar were included
      in this randomized and double-blind study. They received (vo) Rheumazin or
      Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain
      was determined by a visual analogue scale and by the need for escape analgesia
      (paracetamol). Facial swelling was evaluated with a measuring tape and adverse
      effects and patient satisfaction were recorded. There was no statistically
      significant difference in facial swelling between Rheumazin and Feldene (control
      group). Both drugs were equally effective in the control of pain, with Rheumazin
      displaying less adverse effects than Feldene. Therefore, Rheumazin appears to
      provide a better risk/benefit ratio in the mandibular molar surgery. Since the
      side effects resulting from nonsteroidal anti-inflammatory drug administration
      are a severe limitation to the routine use of these drugs in clinical practice,
      our results suggest that Rheumazin can be a good choice for third molar removal
      treatment.

PMID- 16981051
TI  - Luteal phase of the menstrual cycle increases sweating rate during exercise.
AB  - The present study evaluated whether the luteal phase elevation of body
      temperature would be offset during exercise by increased sweating, when women are
      normally hydrated. Eleven women performed 60 min of cycling exercise at 60% of
      their maximal work load at 32 degrees C and 80% relative air humidity. Each
      subject participated in two identical experimental sessions: one during the
      follicular phase (between days 5 and 8) and the other during the luteal phase
      (between days 22 and 25). Women with serum progesterone >3 ng/mL, in the luteal
      phase were classified as group 1 (N = 4), whereas the others were classified as
      group 2 (N = 7). Post-exercise urine volume (213 +/- 80 vs 309 +/- 113 mL) and
      specific urine gravity (1.008 +/- 0.003 vs 1.006 +/- 0.002) changed (P < 0.05)
      during the luteal phase compared to the follicular phase in group 1. No menstrual
      cycle dependence was observed for these parameters in group 2. Sweat rate was
      higher (P < 0.05) in the luteal (3.10 +/- 0.81 g m-2 min-1) than in the
      follicular phase (2.80 +/- 0.64 g m(-2) min(-1)) only in group 1. During
      exercise, no differences related to menstrual cycle phases were seen in rectal
      temperature, heart rate, rate of perceived exertion, mean skin temperature, and
      pre- and post-exercise body weight. Women exercising in a warm and humid
      environment with water intake seem to be able to adapt to the luteal phase
      increase of basal body temperature through reduced urinary volume and increased
      sweating rate.

PMID- 16981052
TI  - Persistent atrial fibrillation as a prognostic factor of outcome in patients with
      advanced heart failure.
AB  - INTRODUCTION: Chronic heart failure (CHF) is associated with high morbidity and
      mortality and is diagnosed more and more frequently. Fifteen to 30% of patients
      with systolic CHF develop atrial fibrillation (AF). AIM: To establish whether
      persistent AF was an independent predictor of mortality, and had a predictive
      value with respect to late clinical outcomes in patients with systolic CHF.
      METHODS: Analysis comprised 120 men with systolic CHF. In 35 (58%) patients CHF
      was the result of ischaemic heart disease and in 25 (42%)--idiopathic dilated
      cardiomyopathy (DCM). Presence or absence of AF was a criterion of patients'
      subsequent division into two subgroups. Sixty patients with AF were assigned to
      the AF group. The control group involved 60 individuals with CHF and sinus rhythm
      (SR) on enrollment. Mean follow-up time was 36 months. RESULTS: Overall 59 (49%)
      patients died during 3-year follow-up, including 33 (56%) in the AF group. Deaths
      were noted more often in CHF patients with underlying ischaemic heart disease
      than DCM (66% vs 34%). This difference reached statistical significance in the AF
      group (72% vs 28%, p<0.001). Moreover, patients with AF more often complained of
      palpitations (p<0.01), had worse exercise capacity (p<0.01) as well as more
      frequently presented complex ventricular arrhythmia (p<0.01). The rate of
      hospital readmission was also higher (p<0.02). In univariate as well as
      multivariate analysis, AF was not found to be an independent predictor of
      mortality. Factors with a potential impact on adverse prognosis were concomitant
      complex ventricular arrhythmias (p=0.01), diabetes (0.04) and reduced exercise
      capacity (p<0.01). CONCLUSIONS: Persistent AF is not an independent risk factor
      of death in patients with advanced systolic CHF. However, it has an unfavourable
      impact on functional status. Concomitant complex ventricular arrhythmias and
      reduced exercise capacity worsen prognosis in this group of patients.

PMID- 16981053
TI  - Endothelium-dependent acetylcholine-induced vasodilatory response of saphenous
      vein grafts.
AB  - INTRODUCTION: It has been suggested that endothelial dysfunction is critical to
      saphenous vein graft (SVG) occlusion. AIM: To evaluate in vivo endothelium
      mediated vasoreactivity in angiographically non-stenotic SVG. METHODS: The group
      consisted of 31 patients (pts), aged 58.7+/-8.7 years, 54+/-38 months after
      coronary bypass surgery. In each patient one angiographically normal SVG was
      selected for the study. Endothelium-dependent vasoreactivity was investigated
      with acetylcholine (Ach) 50 microg intragraft infusion. Graft diameter changes
      were measured by quantitative computer angiography (QCA). RESULTS: In 17 (54.8%)
      pts there was a significant reduction in graft diameter following Ach infusion,
      from 3.8+/-0.7 to 3.2+/-0.7 mm (p=0.0001), whereas in 4 (12.9%) pts there were no
      diameter changes (3.2+/-0.7 mm). In the 10 remaining pts (32.3%) we found graft
      dilatation from 3.5+/-0.5 mm to 3.9+/-0.5 mm (p=0.0002). In multivariate linear
      regression analysis, SVG dilatation positively correlated with a low ratio of
      graft/artery diameter (p <0.002), high HDL-cholesterol level (p <0.001) and
      absence of hypertension (p <0.03), and negatively correlated with postoperative
      myocardial infarction (p <0.01). CONCLUSIONS: Endothelium-dependent vasodilatory
      response to Ach is present in one third of old SVG. Dilative response to Ach 50
      is better preserved in SVG with smaller difference between graft/grafted artery
      diameters. Adequate matching of the graft/grafted artery diameters probably
      preserves the endothelium-dependent dilative response of the graft.

PMID- 16981054
TI  - Is transport with platelet GP IIb/IIIa inhibition for primary percutaneous
      coronary intervention more efficient than on-site thrombolysis in patients with
      STEMI admitted to community hospitals? Randomised study. Early results.
AB  - INTRODUCTION: The advantage of primary percutaneous coronary intervention (pPCI)
      in the management of ST-elevation myocardial infarction (STEMI) over thrombolytic
      therapy has been demonstrated. However, an optimal medical treatment of STEMI
      patients admitted to regional hospitals without catheterisation facilities has
      not yet been established. Delay in initiation of pPCI resulting from
      transportation to the catheterisation laboratory may diminish the benefits of
      such therapy in comparison with thrombolysis administered in a regional hospital.
      Early initiation of therapy with platelet glycoprotein IIb/IIIa receptor
      inhibitor, which provides protection for the transportation, may be a reasonable
      solution to maintain the advantage of pPCI over thrombolysis alone in STEMI
      patients. METHODS: The studied group comprised patients with STEMI (infarct
      duration time <12 hours, typical clinical and electrocardiographic criteria of
      MI) who were randomly assigned in 13 regional hospitals located 20 to 150 km from
      invasive centre to one of two subgroups, either to thrombolysis in the community
      hospital or to transport after thrombolysis initiation with platelet GP IIb/IIIa
      receptor inhibitor (tirofiban; 10 mg/kg in intravenous bolus in the emergency
      room of the community hospital followed by continuous intravenous infusion of 0.1
      mg/kg/min during transport as well as coronary procedure) in order to receive
      pPCI. All patients with cardiogenic shock on admission were routinely treated
      with PCI and were excluded from the study. RESULTS: 341 patients were included in
      the study (169 were randomised to receive thrombolytic therapy and 172--transport
      with intention to perform PCI). Mean time between onset of MI and randomisation
      was similar in the transport and thrombolysis groups, (139+/-133 min. vs 143+/
      117 min., respectively, p=0.94). Mean infusion time of tirofiban to the beginning
      of PCI in the transport group was 121+/-36 min. Anterior MI was present in 42.6%
      of patients in the PCI group and in 41.5% in the thrombolytic group (p=0.085).
      Mean time from randomisation to pPCI was 158+/-60 min., and to thrombolysis
      initiation in 44+/-43 min. (p <0.0001). None of the patients died during
      transfer. In a 30-day follow-up we noted (pPCI vs thrombolytic group,
      respectively): mortality 3.49% vs 8.88% (p=0.04); reinfarction 1.16% vs 5.92%
      (p=0.02), stroke 0.58% vs 1.18% (p=0.55). In-hospital stay was significantly
      shorter in the transport group (9+/-3 days vs 14+/-7 days, p <0.0001). During
      hospitalisation, 17 (10.05%) patients initially assigned to thrombolysis alone
      had to be transferred to the catheterisation laboratory to undergo PCI (rescue
      PCI or PCI for postinfarction angina). Combined end-point
      (death/reinfarction/stroke) was reached more frequently in the thrombolytic group
      (15.98% vs 5.23%, p=0.001). CONCLUSIONS: A strategy of invasive therapy involving
      transport with GP IIb/IIIa receptor inhibitor and pPCI in STEMI patients admitted
      to hospital without catheterisation facilities was found to be more effective
      than thrombolytic therapy alone employed in the regional hospitals.

PMID- 16981055
TI  - Increased levels of inflammatory markers in hypertensives with target organ
      damage.
AB  - INTRODUCTION: Inflammatory markers have been reported to be elevated in
      hypertension. AIM: We compared levels of inflammatory markers between
      hypertensives (HT) with target organ damage (TOD) but without associated clinical
      conditions (ACC), n=55, HT with ACC, n=42, HT without TOD/ACC, n=22 and
      normotensive controls, n=41. METHODS: Serum levels of CRP, fibrinogen, TNF-alpha
      and anti-HSP60 antibodies were measured. Hypertensive complications were assessed
      on the basis of clinical history and the following investigations: M-mode
      echocardiography (left ventricular hypertrophy), Doppler: mitral and pulmonary
      vein flow and isovolumetric relaxation time (diastolic dysfunction), vascular
      ultrasound (common carotid artery intima-media thickness--IMT), pulse wave
      velocity (carotid-femoral arterial stiffness) and creatinine concentration (renal
      function). RESULTS: HT with TOD had higher concentrations of CRP than controls
      (1.71 vs 0.76 mg/l, p <0.0001); higher fibrinogen and TNF-a vs controls and also
      vs HT without TOD/ACC (2.80 vs 2.53 vs 2.49 g/l, p <0.0001) and (2.49 vs 2.00 vs
      1.83 pg/ml, p=0.04), respectively. HT without TOD/ACC did not differ from the
      control group in inflammatory marker concentrations. HT with ACC did not differ
      from HT with TOD in inflammatory marker concentrations. There were no differences
      in anti-HSP60 antibody concentrations between all groups. In multiple regression
      analysis only IMT was influenced by inflammatory markers: fibrinogen (beta=0.2,
      p=0.02) and TNF-alpha, (beta=0.17, p=0.05). CONCLUSIONS: We conclude that
      inflammatory markers are elevated in HT with TOD and are not elevated in
      uncomplicated HT without TOD.

PMID- 16981056
TI  - Dilated cardiomyopathy caused by LMNA mutations. Clinical and morphological
      studies.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is familial in about 20-35% of patients.
      The most frequently encountered mutations associated with DCM are found in LMNA.
      AIM: To define the frequency of LMNA mutations in a series of consecutive DCM
      patients and to evaluate the phenotype of mutation carriers. METHODS: We screened
      the 12 exons of LMNA in a series of 61 Polish patients with DCM diagnosed
      angiographically, as well as in two DCM families. RESULTS: Two mutations were
      detected in 5 mutation carriers (D192G in one proband and Y481Stop in one proband
      and 3 of his offspring), which represents 3.3% (2/61) of the DCM patients. These
      mutations were absent from 100 controls. The D192G mutation was found in a 26
      year-old patient with mild DCM and heart failure leading to death within two
      years after onset of symptoms. Mild conduction disease was also present.
      Ultrastructural analysis of the endomyocardial biopsy showed a striking
      alteration of nuclear morphology. This finding can explain nuclear fragility and
      is in agreement with the pathophysiological mechanical hypothesis of LMNA
      mutations. All four Y481Stop mutation-carriers were affected. Three phenotypes
      were found: in the proband, cardiac dysrhythmia and pacemaker requirement
      preceded DCM leading to heart transplantation; the proband's 13-year old daughter
      had conduction disease (2nd degree A-V block) with subtle skeletal muscle
      involvement documented by immunofluorescence study; ventricular arrhythmia was
      detected in the proband's son at the age of 11 and in the proband's daughter at
      the age of 18. Serum creatine kinase was normal in all mutation carriers.

PMID- 16981057
TI  - [Guidelines on the management of stable angina pectoris; the experts of the
      European Society of Cardiology on the management of stable angina pectoris].

PMID- 16981058
TI  - [Significant aortic stenosis with a low pressure gradient and depressed left
      ventricular function. A case report].
AB  - A 48-year-old man, not diagnosed before, hardly physically working before
      admission, was admitted to cardiological ward at a regional hospital in bad
      condition, with severe heart failure symptoms. Massive calcification of the
      bicuspidal aortic valve was found during the echocardiography examination. Mean
      systolic aortic gradient was 32 mmHg. Left ventricular ejection fraction was
      reduced to 20%. The patient was treated with diuretics, digitalis, dobutamine and
      dopamine infusion but his condition was getting worse. On the 10th day of
      hospitalisation, he was transferred to cardio-surgical ward and aortic valve was
      replaced. On the 15th day following operation the patient came back to the
      regional hospital in good condition. The echocardiography examination revealed an
      increase in systolic ejection fraction of the left ventricle up to 48% in one
      month and to 55% in six months after surgery.

PMID- 16981059
TI  - [Post-infarction left ventricular pseudoaneurysm associated with minor clinical
      symptoms. A case report].

PMID- 16981060
TI  - [The extreme curvature of the coronary artery as a possible cause of myocardial
      infarction. A case report].
AB  - A case of a 60 year old female with angina and remote myocardial infarction is
      presented. Coronary angiography revealed an extreme curvature of the right
      coronary artery which was the most probable cause of infarction. A coronary stent
      was implanted which resulted in clinical improvement.

PMID- 16981061
TI  - [Ventricular septal rupture complicating surgically treated left ventricular free
      wall rupture in a patient with acute myocardial infarction. A case report].
AB  - There is a group of rare but serious complications of acute myocardial infarction
      (AMI), including free wall rupture (FWR) and, less frequent, ventricular septal
      rupture (VSR). Urgent surgery combined with simultaneous CABG is usually a
      treatment of choice. We present a case of a 65-year-old male with AMI, who
      developed cardiogenic shock due to cardiac tamponade as a result of FWR. The
      patient was successfully resuscitated and operated. During postoperative
      treatment parasternal systolic murmur was audible and VSR diagnosis was
      confirmed. Three months after AMI the AMPLAZER Muscular VSD Occluder was
      successfully implanted. The follow-up period was uneventful.

PMID- 16981062
TI  - [Angiogenin--new important parameter in the assessment of ischaemic heart
      disease?].

PMID- 16981063
TI  - [Prinzmetal's angina].

PMID- 16981064
TI  - [Three-dimensional echocardiography for the assessment of the efficacy of
      resynchronisation therapy in a patient with dilated cardiomyopathy and Sjogren's
      syndrome].

PMID- 16981065
TI  - [Acute in-stent thrombosis caused by delayed circular dissection of the right
      coronary artery treated with additional stent implantation and abciximab
      infusion].

PMID- 16981066
TI  - [Post-traumatic stress disorder in a patient with recurrent ICD shocks. The role
      of RF ablation].
AB  - In patients with frequent ICD discharges an acute stress disorder (ASD), and
      afterwards a post-traumatic stress disorder (PTSD) is commonly observed. We
      present a case of a 53-year-old patient with ASD and PTSD in whom RF ablation of
      VT was performed. After the successful procedure the symptoms of PTSD were
      significantly diminished. We conclude that in patients with PTSD after ICD
      discharges RF ablation should be performed as soon as possible.

PMID- 16981067
TI  - [Commentary to the article: Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab
      in patients with acute coronary syndromes undergoing percutaneous coronary
      intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial.
      JAMA 2006; 295: 1531-8].

PMID- 16981068
TI  - [Surgical reconstruction of impaired left ventricle following myocardial
      infarction].

PMID- 16981069
TI  - Clinical course of collagenous colitis over a period of 10 years.
AB  - AIM: The aim of this study was to evaluate the long-term outcome of patients with
      collagenous colitis 10 years after the diagnosis. PATIENTS AND METHODS: In
      1989/1990, 65 patients were diagnosed to have collagenous colitis. Initially and
      after an interval of ten years these patients were asked to complete a
      questionnaire including onset and duration of diarrhea, stool frequency and
      consistency, other gastrointestinal symptoms including weight loss, drug history,
      treatment response and concomitant diseases. RESULTS: Questionnaires from 47
      patients (72.3 %) (female 40; mean age 68 years, range 41 - 95 years) were
      available for analysis. After a follow-up of ten years, 11 patients (23.4 %) had
      persistent diarrhea with no change of frequency and consistency compared to
      baseline. Four patients (8.5 %) showed a reduction of diarrhea frequency of at
      least 50 %. Diarrhea was resolved in 23 patients (48.9 %) during the follow-up
      period. Of those, 20 patients received anti-inflammatory treatment. After a
      complete resolution of diarrhea during the long-term follow-up, 9 patients (19.2
      %) showed recurrence of diarrheal symptoms. None of the patients developed any
      malignancies of the GI-tract. CONCLUSION: The long-term outcome of CC is benign
      with a resolution of diarrhea in up to 50 % of patients receiving anti
      inflammatory treatment. About 30 % of patients may experience persistent diarrhea
      even 10 years after diagnosis. Our data confirm that CC is a chronic disorder
      with a variable course of symptoms during a long-term follow-up.

PMID- 16981070
TI  - ["Iatrogenic acute coronary syndrome"--59 year old patient with adenocarcinoma of
      ascending colon and stenocardia while receiving adjuvant chemotherapy with 5
      fluorouracil].
AB  - Fluorouracil-associated cardiotoxic adverse events represent a relevant but
      underestimated problem in 5-fluorouracil treatment. After right hemicolectomy for
      adenocarcinoma of the rightsided colonic flexure a 59-year old patient was
      referred to our hospital for adjuvant chemotherapy according to MOSAIC-protocol
      with oxaliplatin and 5-fluorouracil. The patient's history was unremarkable for
      any cardiopulmonary disease and for any cardiovascular risk factors. 24 hours
      after completing the first cycle the patient was readmitted to our emergency
      department because of thoracic pain combined with significantly elevated cardiac
      enzymes and ischaemic changes in ECG. Coronary angiography was performed
      revealing no coronary artheriosclerosis. Clinical symptoms and pathological
      ischaemic serum parameters returned to normal range within 12 hours. Diagnosis of
      5-FU-induced acute coronary syndrome could be made. Because of the high rate of
      recurring cardiotoxicity the patient's chemotherapy was modified to an
      alternative regimen containing raltitrexed instead of 5-fluorouracil. Immediate
      diagnosis of 5-FU-induced cardiotoxicity and differentiation from preexisting
      coronary heart disease is still a major problem in daily oncological practice.

PMID- 16981072
TI  - [The enteric glia and neurotrophic factors].
AB  - Enteric glia cells (EGCs) play an important role in the maintenance of tissue
      integrity in the gastrointestinal tract. Thus, genetic ablation of glial
      fibrillary acidic protein (GFAP)-positive EGCs in mice induced fatal haemorrhagic
      jejuno-ileitis and led to death within a few days. The exact mechanisms of EGC to
      contribute to gut homeostasis remain enigmatic. Several lines of evidence
      implicate that the secretion of neurotrophic factors by EGC may be a part of the
      glial regulation of gut homoeostasis. The secretion of glia cell-derived
      neurotrophic factor (GDNF), nerve growth factor (NGF) and transforming growth
      factor-beta (TGF-beta) contributes to the maintenance of epithelial integrity and
      the secretion of endothelins might be involved in vasoregulation. These new
      aspects of intestinal glial functions implicate new therapeutic strategies for
      diseases like Crohn's disease and irritable bowel syndrome.

PMID- 16981071
TI  - Recurrent obscure gastrointestinal bleeding caused by aorto-enteric fistula.
AB  - Aorto-enteric fistulas are rare but serious clinical conditions that may arise as
      a complication following abdominal aortic surgery. Clinical symptoms in affected
      patients range from obscure recurrent gastrointestinal bleeding and intermittent
      unexplained fever attacks to fulminant hematochezia and rapid exsanguination. A
      high degree of clinical alertness and suspicion is critical for both accurate
      diagnosis and timely surgical therapy in these patients. This case report
      describes a patient who was referred to our department six months after abdominal
      aortic surgery. The patient presented with septic illness and episodes of obscure
      gastrointestinal bleeding. Diagnostic work-up revealed a retroperitoneal
      infection of the aortic graft. A false aneurysm led to recurrent duodenal
      bleeding, which was accompanied by perforation of the obliterated aortic graft
      into the cecum. After immediate surgical repair, the patient recovered and
      continues to do well. We present a brief review of the current literature on this
      entity, outlining different surgical strategies and their outcomes.

PMID- 16981073
TI  - [Ultrasound in gastroenterology--liver and spleen].
AB  - Conventional B-mode and colour duplex imaging is the first choice imaging
      technique after history taking and physical examination and for the
      interpretation of laboratory parameters. In the hands of a gastroenterologist
      ultrasound has become an equally important diagnostic tool as endoscopy. The
      constantly evolving technique with its possibility of higher resolution by use of
      "harmonic imaging" and signal enhancement with contrast medium is the reason for
      a practically relevant review of the situation. Practical references will be
      given for diagnostics of the liver and portal system including the spleen. The
      significance of the sonographic diagnosis of "fatty liver" is critically
      discussed. The overall importance of ultrasound to distinguish different
      aetiologies of diffuse liver diseases is relatively low. Nevertheless, it is a
      very sensitive means to detect complications of liver cirrhosis. Portosystemic
      shunts and typical changes in blood vessel morphology can be diagnosed by colour
      duplex sonography and used as indirect signs of advanced damage to liver
      parenchyma. In addition, ultrasound has its value in the confirmation or
      exclusion of dilated bile ducts as well as in the detection and differentiation
      of circumscribed liver lesions. The characterisation of focal liver lesions by
      ultrasound is sufficient in typical cases. The use of ultrasound contrast media
      (signal enhancers) raises the rate of differentiation and can avoid the
      uncritical and sequential application of radiological imaging (computed
      tomography [CT] or magnetic resonance imaging [MRI]). If in doubt about the
      nature of a lesion, a histological diagnosis remains indispensable. The
      examination of the spleen and its feeding vessels is regularly done in cases of
      diffuse parenchymal liver disease when searching for its complications, e. g.,
      portal hypertension. Focal spleen lesions can be observed especially in the
      context of lymphoma (infiltration) and other bone marrow diseases. Through the
      application of contrast media, changes of vascularisation (e. g., infarcts) can
      be visualised and traumatic lesions can be diagnosed more precisely.

PMID- 16981074
TI  - [Fecal methylated DNA for the detection of colorectal cancer].

PMID- 16981075
TI  - [Octreotide versus octreotide plus interferon-alpha in endocrine
      gastroenteropancreatic tumors].

PMID- 16981076
TI  - [Smoke-free restaurants: opinions and acceptance in a representative sample of
      the German population].
AB  - BACKGROUND AND OBJECTIVE: Every year over 3,300 non-smokers in Germany die from
      diseases caused by passive smoking. It was the aim of this study to obtain
      country-wide representative opinions about a smoking ban in restaurants. MATERIAL
      AND METHODS: Data were obtained from a cross-sectional sample of the population,
      2,008 men and women aged 16 years or over. Opinions on smoking ban in restaurants
      were analysed by bivariate and multivariate methods with regard to potential
      influencing factors such as smoking status and socio-demographic status. RESULTS:
      The majority of those questioned, namely 50% (95% confidence interval 57-61),
      wished for a smoking ban in restaurants. This represents an increase of 6%
      compared with the preceding year. While over 82% of never-smokers and 71% of
      previous smokers were in favor of a smoking ban, agreement for a ban among
      smokers averaged 25%, depending on the amount smoked. Agreement was especially
      common among women, the elderly and married persons. Three of four Germans said
      that they would continue to go to restaurants as frequently after smoking had
      been banned there. CONCLUSION: This is the first scientific study of opinions
      among the population on the smoking ban in restaurants of Germany. The current
      average approval rate for a ban was comparable to that among other nations. An
      overwhelming majority of the population would welcome a smoking ban and would,
      after its introduction, visit restaurants as often as previously.

PMID- 16981077
TI  - [Outcome of preliminary proceedings against medical practitioners suspected of
      malpractice].
AB  - BACKGROUND AND OBJECTIVE: There are no reliable data in Germany on the incidence
      of medical malpractice, preliminary proceedings against medical practitioners and
      the results of such proceedings. Preliminary proceedings are especially felt by
      medical practioners to be a significant burden on them. MATERIAL AND METHODS: A
      retrospective study was carried out of all criminal proceedings involving
      accusations of medical malpractice, dealt with at the Institute of Forensic
      Medicine of the University of Bonn between 1989 and 2003. RESULTS: The analysis
      comprised 210 preliminary proceedings. The accusations mainly concerned offences
      against the patient's life or health (negligent bodily injury, section sign 229
      StGB; negligent manslaughter, [section sign] 222 StGB). Most of the preliminary
      proceedings were started without the services of a lawyer representing the
      injured/bereaved. Many accused medical practitioners also had not engaged a
      lawyer, probably because they did not even know of the preliminary proceeding.
      87% of the proceedings were closed according to [section sign] 170 Abs. 2 StPO or
      the verdict was acquittal. 7.6% of the cases were completed according to [section
      sign] 153a Abs. 1 StPO or the result was a conviction. CONCLUSION: Preliminary
      proceedings against medical practitioners due to medical malpractice are
      predominantly closed according to [section sign] 170 Abs. 2 StPO. The study
      reveals that, especially in cases ending in death, autopsy findings often
      exonerate medical practitioners from accusations of medical malpractice. Medical
      practitioners themselves should for this reasons officially report the manner of
      death as of undetermined in order to prepare a basis for later objective
      explanation of the cause of death by legal autopsy.

PMID- 16981078
TI  - [Unilateral swollen leg caused by a retroperitoneal ganglioneuroma].
AB  - HISTORY AND ADMISSION FINDINGS: An 84-year-old man was admitted to our hospital
      because of a swollen left leg resembling deep venous thrombosis. Clinical
      conditions favoring thrombosis such as surgery, trauma, malignant tumor or
      immobilization were not evident. His medical and family history were non
      contributory. He denied bowel or bladder dysfunction and did not complain of any
      back pain, discomfort or neurological symptoms. The enlargement of the leg was
      painless and unilateral. There were no deficits on physical examination. The
      neurological status of the patient was unremarkable. INVESTIGATIONS:
      Ultrasonography was performed because deep vein thrombosis was suspected. Color
      coded duplex revealed no thrombus in the veins of the left leg. Both femoral
      veins were compressible. The flow in the femoral vein was much less than in the
      other leg. Computed tomography demonstrated a solid lesion located in front of
      the spine displacing the inferior vena cava. CT-guided biopsy was performed. On
      histological examination it proved to be diagnostic of a ganglioneuroma.
      TREATMENT AND COURSE: Initially low molecular weight heparin was administered.
      Surgical resection was recommended, but the patient opted not to undergo any
      further treatment at that time. Phenprocoumon was recommended to prevent deep
      vein thrombosis. CONCLUSIONS: Ganglioneuroma is a rare, benign, well
      differentiated, slow-growing tumor composed of sympathetic ganglion cells and
      mature stroma with a good prognosis. Its appearance in elderly persons is
      extremely rare and may imitate deep vein thrombosis caused by vessel compression.
      The appropriate treatment is surgical and complete excision is curative.

PMID- 16981080
TI  - [Telomere dysfunction and telomerase: implications for human pathophysiology
      during ageing and chronic diseases].

PMID- 16981081
TI  - [Infectious endocarditis].

PMID- 16981082
TI  - [Systemic mast cell disease with gastrointestinal symptoms--a diagnostic
      questionnaire].
AB  - Systemic mast cell disease often becomes clinically manifest as a mast cell
      mediator activation syndrome with episodic or chronic nonspecific abdominal
      symptoms. As a result of genetic alterations, pathological mast cells have an
      increased proliferation rate as well as accumulation within different organs with
      consequential effect on gastrointestinal secretion, absorption, pain perception
      and motility caused by release of their mediators. These changes may not be
      detected in routine laboratory or imaging methods. This report describes how the
      diagnosis systemic mast cell disease can be established with a diagnostic
      questionnaire based on a synopsis of clinical findings relevant to a mast cell
      mediator activation syndrome.

PMID- 16981083
TI  - [Medical liability in diagnostic errors. Judgement of the High Court of Koblenz
      on 29.06.2006]].

PMID- 16981084
TI  - Study on energy metabolism in perioperative infants.
AB  - OBJECTIVES: To evaluate resting energy expenditure (REE) in surgical infants and
      define the effects of the degree of stress on its level. SUBJECTS AND METHODS:
      Between June 1999 and June 2003 forty-five infants awaiting surgery (boys/girls:
      32/13) from the Department of Pediatric Surgery were entered in the study.
      Indirect calorimetry was used to measure the REE of all the patients before
      operation and 1 - 7 days after operation. Clinical data were collected, including
      age, weight, height, diagnosis, operative method, site and duration, and first
      day postoperative C-reactive protein (CRP) levels. RESULTS: The REE before
      operation did not differ significantly from the postoperative values (paired t
      test, p > 0.05). The predicted REE was significantly higher than the measured REE
      even before and after the operation (p < 0.01). REE values in the first three
      postoperative days were lower in the mild stress group than in the severe
      surgical stress group. CONCLUSIONS: REE variation among the patients is
      relatively large. Changes in REE may be related to the degree of stress.
      Predicted REE values may be not a good reflection of measured REE.

PMID- 16981085
TI  - Tumor model for laparoscopy in pediatric oncology: subperitoneal inoculation of
      human hepatoblastoma cells in nude rats.
AB  - BACKGROUND: Minimally invasive surgery (MIS) for diagnostic or even ablative
      purposes in pediatric oncology is gradually evolving, but little is known about
      its biological consequences and surgical complications. Especially for
      hepatoblastoma (HB), no study on the influence of laparoscopy is available yet. A
      special tumor model could facilitate a variety of investigations. The present
      study introduces a laparoscopic technique to create subperitoneal metastases of
      human HB. METHODS: 7 immuno-incompetent (rnu/rnu) rats (mean weight 198 g)
      received a stab incision in the lower abdomen to insert a 4 mm scope. Under
      laparoscopic guidance (CO2 pressure of 1 mmHg, flow of 0.2 l/min) an 18 G needle
      was introduced, to inject several subperitoneal deposits of the tumor cell
      suspension (HuH6, 3 x 10 (6) in 1 ml of RPMI-1640 medium). Tumor growth was
      allowed for 6 - 7 weeks and finally the animals were laparoscopically evaluated
      for peritoneal metastases. Each suspicious lesion was harvested for histology.
      RESULTS: One animal was investigated after 6 weeks without evidence of tumor
      growth. After 7 weeks, in 4 out of 6 animals at least one lesion could be
      detected. Histology revealed HB in all specimens. CONCLUSION: Subperitoneal
      inoculation of human HB cells in nude rats achieves intraabdominal tumor growth.
      The present model allows a variety of laparoscopic strategies and their
      oncological impact to be studied. Thus it may contribute to the development of
      distinct oncological concepts for MIS in children with HB.

PMID- 16981086
TI  - Management and algorithm for focal nodular hyperplasia of the liver in children.
AB  - PURPOSE: The aim of this study was to determine an appropriate management plan
      for childhood and adolescent FNH, in particular to establish an algorithm for
      preoperative diagnosis and treatment. PATIENTS AND METHODS: Between 1985 and
      2003, 4 children with FNH were diagnosed. Of these 4 patients, 3 (Group A)
      underwent tumor resection, and 1 (Group B) was treated by conservative
      management. Clinical data, pathological findings and follow-up were evaluated
      retrospectively. RESULTS: The 3 patients in Group A were symptomatic, while the 1
      patient in Group B was asymptomatic. In 3 of 4 patients, a homogeneous tumor with
      a central stellate area was noted on abdominal ultrasonography, CT scan and MR
      imaging. In case 2, SPIO-enhanced MR imaging was useful for differentiating FNH
      from hepatocellular carcinoma. Though percutaneous needle biopsy was performed in
      case 3, a pathologically definitive diagnosis was impossible. An open biopsy was
      performed in case 4 and FNH was diagnosed. In case 4 treated by conservative
      management, the tumor size did not change during the 7 years after the diagnosis
      of FNH. CONCLUSION: FNH is usually treated conservatively because of the good
      evolutionary outcome of the lesion. Surgery is indicated in cases of
      complications, compressed adjacent organs, lesion progression, or for symptomatic
      patients. We advocate the use of less invasive SPIO-enhanced MR imaging instead
      of open biopsy when the diagnosis of focal liver lesions is not clear after
      contrast-enhanced CT scan and non-enhanced MR imaging.

PMID- 16981087
TI  - Laparoscopic nephroureterectomy in children: a prospective study on Ligasure
      versus Clip/Ligation.
AB  - PURPOSE: The present study was performed to compare dissection of the renal hilar
      vessels in laparoscopic transabdominal nephrectomy in children using the Endo
      Ligasure vessel sealing system versus clip/ligation. PATIENTS AND METHODS: In a
      prospective and comparative study carried out from February 2003 to April 2004,
      10 consecutive patients (group 1) underwent laparoscopic transabdominal
      nephroureterectomy using clips or intracorporeally performed ligations,
      respectively. From April 2004 to April 2005, 10 consecutive patients (group 2)
      underwent the same procedure using the Endo-Ligasure vessel sealing system.
      Indications for surgery were confirmed non-functioning kidneys secondary to
      benign unilateral renal disease and no prior surgery. The age and underlying
      disease distribution and the affected side were not significantly different
      between the two groups. RESULTS: The operating time was significantly lower in
      the Endo-Ligasure group (group 1: median 167 vs. group 2: 108 min, p < 0.05).
      Bleeding of the renal artery occurred due to dislocation of a suture ligation,
      which was treated laparoscopically with an intracorporeal suture ligation. Blood
      loss was negligible in all patients. All procedures were completed
      laparoscopically and recovery was uneventful. CONCLUSIONS: Endo-Ligasure is a
      beneficial tool in laparoscopic transabdominal nephrectomy. It is safe,
      effective, and reduces operating times compared to clip application and
      intracorporeal suturing.

PMID- 16981088
TI  - Endoscopic correction of vesicoureteric reflux--our thirteen years' experience.
AB  - AIM OF THE STUDY: We review our thirteen years' experience with the endoscopic
      treatment of primary vesicoureteric reflux (VUR). METHODS: We retrospectively
      reviewed the charts of 81 patients with primary vesicoureteric reflux who were
      treated endoscopically. The study included 61 girls and 20 boys aged 3 - 15
      years. Twenty-eight patients had unilateral reflux, and 53 patients had bilateral
      reflux. Endoscopic correction with Teflon paste was done in 64 patients, and
      endoscopic treatment with Deflux was done in 17 patients. A total of 134 ureters
      were treated. RESULTS AND CONCLUSION: Reflux was corrected in 87 ureters (64.9 %)
      after the first injection. The second injection resolved reflux in an additional
      20 ureters (14.9 %). Reimplantation was necessary in 4 patients (4.9 %). Overall
      success rate of the endoscopic treatment was 85.0 %. Reflux was completely absent
      in 79.8 % of the treated patients, and 5.2 % of the patients had a decreased
      grade of reflux after the procedure. Treatment was unsuccessful in 3.0 % of the
      patients. In seven patients spontaneous resolution of the persisting reflux
      occurred. Endoscopic correction should be performed in all patients with grade
      two, three and four reflux. Grade one reflux should be treated conservatively,
      and grade five reflux should be treated surgically. Since Deflux is a
      biodegradable material, most of the patients should be treated bilaterally, even
      if they have only grade one reflux. Endoscopic correction of primary
      vesicoureteric reflux is an easy, simple, fast and safe procedure that, in most
      cases, prevents regurgitation of urine from the bladder to the upper parts of the
      urinary system.

PMID- 16981089
TI  - Antegrade continence enema--an analysis of 20 children with faecal incontinence.
AB  - AIM OF THE STUDY: We present our experience with the Malone antegrade continence
      enema technique in children suffering from severe anal incontinence. METHODS: The
      Malone antegrade continence enema technique was performed using the appendix,
      caecum or ileum in 20 children with faecal incontinence. The stoma was kept
      catheterised for three weeks after the operation in all patients and irrigation
      with saline was initiated after that period. Tap water was used for irrigations
      after discharge from hospital. The functional success was evaluated according to
      the classification defined by Curry et al. RESULTS: The mean age and the mean
      follow-up period was 11 years and 5 years, respectively. Strictures developed in
      five of the 20 cases (25 %) in this series. Four of these patients underwent
      revisional surgery, but in one case with appendiceal tube the stricture and
      catheterisation difficulty resolved spontaneously. Full continence was achieved
      in 13 of the children (65 %). CONCLUSIONS: The Malone procedure is an effective
      procedure in children with faecal incontinence. It should be performed after
      confirming that the patient is completely clean using Pena's programme and aften
      ensuring that both the child and the parents will properly follow the
      recommendations.

PMID- 16981090
TI  - Rare injuries to the distal tibiofibular joint in children.
AB  - Injuries to the distal tibiofibular junction have been very precisely described
      in adults including diagnosis and treatment. By comparison, only two types of
      epiphyseal fracture were described as the equivalent of such an injury in the
      growing skeleton until now: the juvenile Tillaux fracture and the lateral
      triplane fracture. During a five-year period (1997 - 2001) twenty children with
      distal tibiofibular joint injury were treated in our department. Three previously
      unpublished types of epiphyseal injury to the distal tibial mortise are
      presented: intraepiphyseal fractures of Chaput's tubercle type 7A and 7B
      according to Ogden's classification (in two and one cases, respectively) and an
      intraepiphyseal subcortical tibial mortise disruption (one case). The authors
      suggest that these three types are transitive types between juvenile Tillaux
      fracture in children and disruption of the distal tibiofibular syndesmosis in
      adults. All three types were without significant displacement and were stable in
      stress positions of the ankle joint. Thus, the treatment was nonoperative with
      excellent results and without sequelae.

PMID- 16981091
TI  - Congenital oesophageal atresia discordant for tracheo-oesophageal fistula
      occurring in a set of dizygotic twins.
AB  - The authors present a set of female diamnionic and dichorionic twins with
      different blood types and congenital oesophageal atresia (EA) in both. Surgical
      management was successful. It can be assumed that EA with tracheo-oesophageal
      fistula in twin B occurred during an early embryological stage whereas the
      isolated EA in twin A was the result of a later event. To our knowledge, this is
      the first published set of dizygotic twins with different types of EA.

PMID- 16981092
TI  - Endobronchial tuberculous granuloma in children.
AB  - Endobronchial tuberculosis is rare in children, in whom it is usually a
      complication of primary tuberculosis. Endobronchial involvement may adopt several
      forms, with granuloma being infrequent. Here we report on 10 cases of
      endobronchial tuberculous granuloma diagnosed and treated in our Paediatric
      Surgery Service between 1991 and 2004. In 2 cases the presentation was acute and
      constituted the first manifestation of TB; the remaining patients were undergoing
      treatment or had been treated for primary TB, and presented with clinical
      symptoms or radiological signs that led us to suspect endobronchial involvement.
      In all cases the granuloma was removed by bronchoscopy. Patients received
      conventional medical TB treatment, with corticoids for 4 weeks following
      granuloma removal. The clinical course was favourable in all cases and on follow
      up we saw no complications. Endobronchial tuberculous granuloma should be borne
      in mind in children with symptoms or signs of airway obstruction and especially
      during the course of tuberculosis treatment.

PMID- 16981093
TI  - Radiology cases from the Royal Hospital for Sick Children, Glasgow: biloma as a
      complication of hepatic transection due to a handlebar injury.
AB  - Handlebar type injuries are well documented in the paediatric population. We
      describe a case complicated by a biloma, which was successfully treated with
      percutaneous drainage, guided radiologically. The imaging findings including CT,
      MRI and nuclear medicine techniques are presented.

PMID- 16981094
TI  - Post traumatic intra-abdominal pseudo-aneurysms in children.
AB  - Pseudoaneurysms are uncommon following blunt abdominal trauma. A review of the
      literature has shown that such cases are usually managed aggressively. We report
      our experience of two cases of post traumatic intra-abdominal pseudoaneurysms
      which were managed conservatively.

PMID- 16981095
TI  - Antiretroviral agents mimicking functional neonatal bowel obstruction: a case
      report.
AB  - A group of neonates born by elective Caesarean delivery to HIV infected mothers
      taking the antiretroviral agent Zidovudine, are presented. The three newborns
      were also treated with Zidovudine immediately postnatally, and developed
      functional distal bowel obstruction. The bowel obstruction resolved with
      conservative management and cessation of the oral antiretroviral agent. The
      combination of caesarian delivery and antiretroviral agents should be considered
      as a possible cause for delayed meconium passage and a functional distal bowel
      obstruction.

PMID- 16981096
TI  - Ureteral triplication--report of four cases.
AB  - Four cases of ureteral triplication in children are described. In one case
      ureteral triplication was detected incidentally and it was not accompanied by any
      other pathology of the urinary tract. In the three remaining cases there were
      pathologies of the urinary system (reflux, obstruction) that demanded surgical
      treatment. The literature concerning this rare anomaly is reviewed.

PMID- 16981097
TI  - Abdominoscrotal hydrocele--is there a place for conservative management?
AB  - Abdominoscrotal hydrocele (ASH) is an uncommon entity. It consists of large
      inguinoscrotal swelling which is dumbbell shaped, and in theory, communicates
      with its intra-abdominal component. Although various theories have been proposed,
      the aetiology is still unclear. To date, the only reported management is by
      surgical excision. Spontaneous resolution has not been documented in the
      literature. We present a case of proven abdominoscrotal hydrocele successfully
      managed by conservative approach.

PMID- 16981098
TI  - Cervicothoracic malignant peripheral nerve sheath tumor in a 12-year-old girl
      with neurofibromatosis type 1.
AB  - We encountered a 12-year-old girl with neurofibromatosis type 1 (NF1) who
      developed a low-grade cervicothoracic malignant peripheral nerve sheath tumor
      (MPNST). Computed tomography of the neck showed an elastic firm tumor measuring 7
      x 6 x 4 cm and arising from the upper mediastinum. She had no pain or
      neurological symptoms, but the tumor enlarged to ca. 8 x 8 x 4 cm over the
      following 7 months. Although we had diagnosed a neurofibroma by preoperative
      incisional biopsy, the resected tumor showed low-grade MPNST in the central
      portion of the tumor. In treating a tumor in a patient with NF1, we must
      recognize that partial biopsies do not necessarily establish a definitive
      diagnosis and that a growing tumor may indicate malignant transformation.

PMID- 16981099
TI  - Amputation neuroma following a circumcision: a case report.
AB  - We present a case of neuroma formation following the circumcision of an 11-year
      old boy. Amputation neuroma is an extremely rare clinical finding. In the
      literature only a few cases of amputation neuroma have been reported, mainly
      located in the biliary tract, in the cystic duct, or in the main hepatic duct
      after cholecystectomy [1, 4, 8]. There are also few reported cases localised at
      the orbit, on the great auricular nerve [2], and in the neck after radical neck
      dissection for oral cancer [5, 7]. Neuroma formation has also been reported after
      digital amputation [6]. The only reported case of genital amputation neuroma is
      in a 27-year-old infibulated African woman [3].

PMID- 16981100
TI  - Intra-articular recurrence of benign chondroblastoma with articular involvement
      at initial presentation--a case report.
AB  - We report a case of chondroblastoma involving the upper tibial epiphysis, which
      had an unusually aggressive course, with articular involvement at initial
      presentation. Intra-articular and soft tissue recurrence occurred after treatment
      consisting of curettage and bone grafting. Although the incidence of local
      intraosseous recurrence of chondroblastoma is relatively high, intra-articular
      and soft tissue implantation is rare and is usually due to intra-articular
      spillage during surgery. Spontaneous articular involvement is rarely seen.

PMID- 16981101
TI  - Additional muscle in idiopathic club foot.
AB  - During the dissection of seven club feet of foetuses, aborted between the 25th
      and 37th week of gestation, an additional muscle bundle was found in a right
      foot. This muscle arose from both heads of the gastrocnemius muscle, continued
      downwards onto the posterior surface of the soleus, crossed the calcaneal tendon
      and assumed a position on the lateral side of the calcaneal tendon. The muscle's
      tendon was fixed just laterally to the calcaneal tendon in the calcaneal
      tuberosity with some tiny fibres branching off into the superior fibular
      retinaculum.

PMID- 16981102
TI  - Autofluorescence endoscopy in surveillance of Barrett's esophagus: a multicenter
      randomized trial on diagnostic efficacy.
AB  - BACKGROUND AND STUDY AIMS: The reference surveillance method in patients with
      Barrett's esophagus is careful endoscopic observation, with targeted as well as
      random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it
      easier to locate neoplasia. The aim of this study was to elucidate the diagnostic
      accuracy of surveillance with AFE-guided plus four-quadrant biopsies in
      comparison with the conventional approach. PATIENTS AND METHODS: A total of 187
      of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 %
      male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent
      endoscopy for Barrett's esophagus in four study centers, were randomly assigned
      to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or
      conventional endoscopic surveillance, also including four-quadrant biopsies
      (study phase 1). After exclusion of patients with early cancer or high-grade
      dysplasia, who underwent endoscopic or surgical treatment, as well as those who
      declined to participate in phase 2 of the study, 130 patients remained. These
      patients were examined again with the alternative method after a mean of 10
      weeks, using the same methods described. The main study parameter was the
      detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing
      both approaches in study phase 1; the secondary study aim in phase 2 was to
      assess the additional value of the AFE-guided approach after conventional
      surveillance, and vice versa. Test accuracy measures were derived from study
      phase 1. RESULTS: In study phase 1, the AFE and conventional approaches yielded
      adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis.
      With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified
      (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %)
      was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE
      endoscopy in study phase 1, eight were visualized, while 11 were only detected
      using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies
      classified at histology as being nonneoplastic, 58 appeared suspicious
      (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5
      %). In study phase 2, AFE detected two further lesions in addition to the initial
      alternative approach in 3.2 % of cases, in comparison with one lesion with
      conventional endoscopy (1.7 %). CONCLUSIONS: In this referral Barrett's esophagus
      population with a higher prevalence of neoplastic lesions, the AFE-guided
      approach improved the diagnostic yield for neoplasia in comparison with the
      conventional approach using four-quadrant biopsies. However, AFE alone was not
      suitable for replacing the standard four-quadrant biopsy protocol.

PMID- 16981103
TI  - Upper gastrointestinal endoscopy does not reassure patients with functional
      dyspepsia.
AB  - BACKGROUND AND STUDY AIMS: Upper gastrointestinal endoscopy in patients with
      functional dyspepsia is often carried out merely to reassure patients that
      symptoms are not due to serious pathology. The aim of this study was to compare
      anxiety, depression, and health-related quality of life as proxy values for
      reassurance in patients with functional dyspepsia before and after upper
      gastrointestinal endoscopy. PATIENTS AND METHODS: Consecutive patients referred
      for endoscopy between February 2002 and February 2004 were included in the study.
      They were asked to score anxiety and depression using the Hospital Anxiety and
      Depression Scale, health-related quality of life using the EuroQol-5D
      questionnaire, and their impression of their own general health using a visual
      analogue scale, 2 weeks before endoscopy and again 1 month afterwards. RESULTS: A
      total of 420 patients were included, 42 % of whom were found to have an organic
      abnormality of some sort during upper gastrointestinal endoscopy. Neither the
      anxiety nor the depression frequencies differed significantly before and after
      endoscopy, either in patients with organic abnormalities at endoscopy or in those
      without. The general impression of health did not change after endoscopy either:
      organic abnormalities 62.7 +/- 27.4 vs. 64.9 +/- 24.2, P = 0.28; functional
      dyspepsia 61.0 +/- 27.9 vs. 62.8 +/- 27.2, P = 0.39. Only patients who had
      organic abnormalities reported a slightly improved quality of life 1 month after
      endoscopy: 0.74 +/- 0.15 vs. 0.78 +/- 0.12, P < 0.01. CONCLUSION: In patients
      with functional dyspepsia, upper gastrointestinal endoscopy does not improve
      psychological well-being or health-related quality of life. In view of the
      invasiveness, cost, and potential harm associated with endoscopy, careful
      consideration should be given to whether this procedure should be carried out
      merely for the sake of the patient's "peace of mind".

PMID- 16981104
TI  - Development and assessment of morphologic criteria for diagnosing gastric cancer
      using confocal endomicroscopy: an ex vivo and in vivo study.
AB  - BACKGROUND AND STUDY AIMS: The Confocal Endomicroscopy System (Optiscan Pty Ltd.
      and Pentax Corp.) is a newly developed imaging tool that uses laser light and
      optical technology to visualize living tissue at the cellular level. Digital
      images of cells magnified 1000-fold appear in real time on a computer screen,
      which enables immediate detection of changes in cellular structure without the
      need for a biopsy. The aim of this study was to assess the features of the
      cellular architecture of cancerous tissue that can be used in the differential
      diagnosis of cancerous tissue and normal mucosa using this system's image
      processing software. PATIENTS AND METHODS: A total of 27 gastric cancers were
      examined ex vivo using confocal endomicroscopy. A fluorescent contrast agent,
      acriflavine, was applied topically to normal and to cancerous mucosa. In vivo
      imaging of the gastric mucosa after intravenous injection of fluorescein sodium
      was also performed in nine patients with gastritis or gastric cancer. RESULTS:
      The nuclear area in the ex vivo specimens was calculated using Scion Image
      software. The mean nuclear area of cancer cells was found to be significantly
      larger than that of normal cells in 18/27 gastric cancers (67 %). The mean
      nuclear area of the cancers tended to be larger than that of normal mucosa,
      especially in cases of differentiated adenocarcinoma. In more than half the
      cases, it was possible to diagnose malignancy automatically using confocal
      endomicroscopy and image-processing software without the need for biopsy and
      pathological examination. In vivo imaging of cancerous lesions showed
      irregularity in cellularity and vascularity. CONCLUSION: The ability of this
      imaging device to differentiate between normal tissue and cancerous tissues gives
      it potential value as a new screening tool for early detection of malignancy.

PMID- 16981105
TI  - Endoscopic in vivo evaluation of tissue atypia in the esophagus using a newly
      designed integrated endocytoscope: a pilot trial.
AB  - BACKGROUND AND STUDY AIMS: A newly designed magnifying endoscope featuring an
      endocytoscopy function provided by ultrahigh magnification was evaluated in a
      pilot study in patients with various types of benign and malignant pathology in
      the esophagus. PATIENTS AND METHODS: Seventy-five consecutive patients were
      included in the study from 15 March to 21 December 2005. Twenty-nine patients
      with specific esophageal lesions that had been detected by regular or narrow-band
      imaging, or both, were further evaluated using endocytoscopy, followed by tissue
      biopsy or resection. During the endocytoscopic examinations, the esophageal
      mucosa was stained with 0.5 % methylene blue. The endocytoscopic findings were
      graded from 1 to 5 in an endocytoscopic atypia (ECA) classification. The final
      histopathological diagnoses based on biopsies or resected specimens were as
      follows: category 1 in the Vienna classification, n = 4; category 2, n = 6;
      category 3, n = 1; category 4, n = 10; and category 5, n = 7. The endocytoscopic
      diagnoses were compared with the histopathological diagnoses. RESULTS: Clear
      endocytoscopic images were obtained in all cases. In definitely malignant
      lesions, the cell nuclei had an enlarged and irregularly arranged appearance
      (grade ECA 5). The positive predictive value for malignancy (grades ECA 4 and 5)
      was 94 %; the false-negative rate was 16.7 %, and the false-positive rate was 6.3
      %. The overall accuracy of endocytoscopy for differentiating between nonmalignant
      tissue (categories 1 - 3 in the Vienna classification) and malignant tissue
      (categories 4 and 5) was 82 %. CONCLUSIONS: These preliminary results suggest
      that incorporating endocytoscopy facilities into a standard endoscope may be
      helpful in characterizing tissue in a variety of esophageal lesions. The
      potential clinical impact of this method in relation to other gastrointestinal
      organs requires further study.

PMID- 16981106
TI  - The use of self-expanding metal stents to treat acute esophageal variceal
      bleeding.
AB  - BACKGROUND AND STUDY AIMS: Acute variceal bleeding is a life-threatening
      complication of liver cirrhosis. Essential factors for survival after variceal
      bleeding are the rapidity and efficacy of initial primary hemostasis. Endoscopic
      and vasoactive therapy is the gold standard in the management of acute variceal
      hemorrhage. The primary aim of this study was to evaluate the use of self
      expandable metallic stents to arrest uncontrollable acute variceal bleeding.
      PATIENTS AND METHODS: Between November 2002 and May 2005, esophageal stents were
      implanted in 20 patients (18 men, two women; mean age 52, range 27-87) with
      massive ongoing bleeding from esophageal varices, as an alternative treatment to
      balloon tamponade. The patients had not been successfully managed with prior
      pharmacologic or endoscopic therapy. They had had one to five previous bleeding
      episodes (mean 2.4). Eight of the patients were in Child-Pugh grade B and 12 in
      grade C. A new type of stent with special introducers was developed that allowed
      placement without radiographic assistance. RESULTS: The stents were successfully
      placed in all of the patients and were left in place for 2-14 days. Bleeding from
      the esophageal varices ceased immediately after implantation of the stent in all
      cases. While the stent was in place, further diagnostic steps were carried out to
      optimize management of the patients' illness and portal hypertension. No
      recurrent bleeding, morbidity, or mortality occurred during treatment with the
      esophageal stent. All of the stents were extracted without any complications
      after definitive treatment had been started. CONCLUSIONS: In this pilot study,
      the new method of implantation of an esophageal stent was found to be a safe and
      effective treatment for massive bleeding from esophageal varices in patients with
      liver cirrhosis. These initial clinical results will of course have to be
      confirmed in comparative studies including a large number of patients.

PMID- 16981107
TI  - "Salvage" endoscopic mucosal resection in the colon using a retroflexion
      gastroscope dissection technique: a prospective analysis.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection and submucosal dissection
      can provide curative endoscopic therapy for Paris type I/II adenomas and node
      negative early cancer. No studies have addressed the technical feasibility of
      retroflexion endoscopic dissection methods for luminal "salvage" therapy in
      patients considered unresectable using conventional forward-viewing resection.
      PATIENTS AND METHODS: Colonoscopy using an Olympus GIF-XQ240 gastroscope was
      carried out in 76 patients with Paris type I/II adenomas, early colorectal cancer
      (CRC), or laterally spreading tumors (LSTs) when the index endoscopist considered
      the lesion to be unresectable due to retrograde fold involvement. Endoscopic
      mucosal resection (EMR) and submucosal dissection were carried out using a
      complete retroflexion technique. Endoscopic and miniprobe 20-MHz or 12.5-MHz
      ultrasound follow-up data were collected prospectively up to 24 months after the
      index resection. RESULTS: Cecal intubation or cannulation to the neoterminal
      ileum was achieved in 76 (100 %) cases. Forty lesions (53 %) were classified in
      accordance with the Paris criteria as Is; 16 (21 %) as type II; 10 (13.5 %) as
      LST-G; and 10 (13.5 %) as LST-NG. Eight lesions (10 %) were excluded from EMR on
      the basis of endoscopic ultrasound criteria, with 68 of the 76 lesions (89 %)
      meeting the criteria for endoluminal resection. The median intubation time was 16
      min (range 3-32 min). The median resection times were 98 min (range 30 - 242
      min), 36 min (range 10-60 min), 172 min (range 20 - 240 min), and 60 min (range
      10-116 min) for Paris Is, II, LST-G, and LST-NG lesions, respectively. LST-G
      morphology was associated with a high median submucosal injection volume in
      comparison with all other Paris types ( P < 0.05) and with a prolonged resection
      time ( P < 0.01). Sixty-one patients (94 %) completed the surveillance protocol.
      Higaki recurrence criteria were met in seven patients (11 %), with six undergoing
      successful adjunctive endoluminal resection. After 24 months of follow-up, the
      "cure" rate with endoscopic resection was 60 out of 61 (98 %). CONCLUSIONS: This
      is the first prospective study to address the safety and medium-term efficacy of
      retroflexion endoscopic resection in the colon. When appropriate exclusion
      criteria are applied, selected patients can receive curative resection using the
      retroflexion technique. "Salvage" endoluminal therapy may therefore be possible
      in such cases when surgical resection would otherwise have been required.

PMID- 16981108
TI  - Evaluation of dextrose 50 % as a medium for injection-assisted polypectomy.
AB  - BACKGROUND AND STUDY AIMS: Injection-assisted polypectomy (IAP) is traditionally
      carried out by using normal saline as the submucosal fluid cushion. However,
      normal saline, being isotonic, does not maintain the elevation of the mucosa for
      prolonged periods. It was hypothesized that dextrose 50 %, as a hypertonic
      solution, might be an ideal medium for IAP. This study evaluated the efficacy and
      safety of dextrose 50 % for performing IAP. PATIENTS AND METHODS: All patients
      undergoing IAP during gastroscopy or colonoscopy were randomly assigned on a
      prospective basis to receive either normal saline or dextrose 50 % as the
      submucosal fluid cushion. The endoscopist was blinded to the type of solution
      injected. The volume of solution and number of sites injected to elevate the
      lesion, the number of times IAP was interrupted to inject more fluid to maintain
      elevation, the rates of en bloc and complete resections, and the complication
      rates were compared in the two groups. The mean follow-up period was 10 months.
      RESULTS: Fifty-two sessile lesions were removed in 50 patients. In comparison
      with normal saline, smaller volumes (median 7 ml vs. 5 ml; P = 0.02) and fewer
      injections (median 2 vs. 1; P = 0.003) were required to perform IAP when dextrose
      50 % was used. The en bloc resection rate was higher with dextrose 50 % than with
      normal saline (82 % vs. 44 %; P = 0.01). Elevation of the submucosal area
      persisted even after completion of IAP in 96 % of the patients randomly assigned
      to dextrose 50 %, compared with 20 % of those receiving normal saline ( P <
      0.001). There were no significant differences in the rates of complete resection
      or complications between the two groups. CONCLUSIONS: Dextrose 50 % is superior
      to normal saline as a submucosal fluid cushion, as it allows better en bloc
      resection during injection-associated polypectomy.

PMID- 16981109
TI  - A simplified ingestion procedure for esophageal capsule endoscopy: initial
      evaluation in healthy volunteers.
AB  - BACKGROUND AND STUDY AIMS: Initial studies on esophageal capsule endoscopy
      (PillCam ESO) reported excellent sensitivity and specificity, but these were
      followed by mixed results in several subsequent studies, probably due to
      deviations from the recommended ingestion protocol and the inconvenience of
      capsule ingestion in the supine position. The aim of this study was therefore to
      test a simplified ingestion procedure (SIP) for PillCam ESO. PATIENTS AND
      METHODS: Using a cross-over study design, the SIP was prospectively compared with
      the original ingestion procedure for PillCam ESO in 24 healthy volunteers (15
      men, nine women; mean age 44, range 27 - 70) and evaluated for: bubbles/saliva
      interference at the Z-line, Z-line circumferential visualization (quadrants), and
      convenience and ease of the ingestion procedure. All Rapid 4 videos were reviewed
      in a randomized manner and read by an experienced PillCam ESO reader blinded to
      the ingestion procedure used. RESULTS: It was found that the SIP significantly
      improved visualization in comparison with the original ingestion procedure, with
      less interference due to bubbles/saliva observed at the gastroesophageal junction
      ( P = 0.002) and improved visualization of the Z-line ( P = 0.025). Although the
      esophageal transit time was significantly faster with the SIP (3 : 45 min vs. 0 :
      38 min; P = 0.0001), there were no differences in the number of Z-line
      frames/images captured. CONCLUSIONS: This new, simplified ingestion procedure for
      PillCam ESO provides significantly improved visualization of the Z-line in
      healthy volunteers. The overall test characteristics of PillCam ESO using SIP
      should be tested in patients with esophageal disease.

PMID- 16981110
TI  - Endoscopic ultrasound-guided fine-needle aspiration biopsy for lymphadenopathy of
      unknown origin.
AB  - BACKGROUND AND STUDY AIMS: The diagnosis of mediastinal and intra-abdominal
      lymphadenopathy is sometimes difficult, especially in patients who have no other
      primary lesions. Lymphoma is one of the main causes of this condition. Endoscopic
      ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe and accurate
      diagnostic procedure for lesions surrounding the gastrointestinal tract. However,
      diagnosing lymphoma using the EUS-FNA technique remains a diagnostic challenge,
      due to limitations in the amount of material sampled. The aim of the present
      study was to evaluate the yield of EUS-FNA biopsy (EUS-FNAB) using a large-gauge
      needle in patients with mediastinal and intra-abdominal lymphadenopathy of
      unknown origin, especially in relation to subclassification of the lymphomas.
      PATIENTS AND METHODS: Consecutive patients with mediastinal and intra-abdominal
      lymphadenopathy of unknown origin who were referred between October 2003 and
      March 2005 were enrolled in the study. EUS-FNAB was carried out using a 19-gauge
      needle, passing through the esophageal, gastric, and duodenal walls. Pathological
      diagnoses were made on the basis of histological findings, including
      immunopathological staining. RESULTS: A total of 104 patients were included in
      the study. The locations of the lymph nodes were mediastinal in 50 patients,
      intra-abdominal in 48 patients, and both mediastinal and intra-abdominal in six
      patients. The diagnoses made using EUS-FNAB were lymphoma (n = 48), metastasis (n
      = 16), and benign/reactive (n = 40). The overall accuracy of EUS-FNAB for unknown
      lymphadenopathy was 98 %, and it was possible to classify the lymphomas in
      accordance with the World Health Organization classifications in 88 % of cases.
      No serious complications occurred with the procedure. CONCLUSIONS: Open thoracic
      surgery, laparotomy, and other invasive diagnostic procedures such as
      mediastinoscopy and laparoscopy can now be avoided, as EUS-FNAB is potentially a
      safe and accurate tool for diagnosing unknown lymphadenopathy, including
      lymphoma.

PMID- 16981111
TI  - Endoscopic necrosectomy as primary therapy in the management of infected
      pancreatic necrosis.
AB  - BACKGROUND AND STUDY AIMS: Open pancreatic necrosectomy is the standard treatment
      for infected pancreatic necrosis but is associated with significant morbidity,
      mortality, and prolonged hospital stay. Percutaneous or endoscopic necrosectomy
      are alternative techniques. We evaluated the use of endoscopic necrosectomy for
      treatment of patients with necrosis that could be accessed through the posterior
      wall of the stomach. PATIENTS AND METHODS: We retrospectively analyzed the
      indication, patient status according to acute physiology and chronic health
      evaluation (APACHE) 2 severity score, and success of endoscopic necrosectomy as
      primary treatment, in selected patients with localized infected pancreatic
      necrosis, who presented between May 2002 and October 2004. After the necrosis
      cavity had been accessed, with the assistance of endoscopic ultrasound, a large
      orifice was created and necrotic debris was removed using endoscopic accessories
      under radiological control. Follow-up was clinical and radiological. RESULTS: 13
      patients (nine men, four women, mean age 53 years), 11 with positive
      bacteriology, underwent attempted endoscopic necrosectomy. Median APACHE 2 score
      on presentation was 8 (range 1-18). Four patients needed intensive therapy unit
      care and one other patient required (nonventilatory) high-dependency unit care
      only. Necrosis was successfully treated endoscopically in 12 patients, requiring
      a mean of 4 endoscopic interventions (range 1-10); one patient required open
      surgery; two underwent additional percutaneous necrosectomy and one required
      laparoscopic drainage. Two patients died of complications unrelated to the
      procedure. The 11 survivors have a median (range) follow-up of 16 (6-38) months.
      CONCLUSION: Endoscopic necrosectomy is a safe method for treatment of infected
      pancreatic necrosis. Multiple procedures are usually needed. It may be combined
      with other methods of surgical intervention. Larger prospective studies will more
      precisely define its role.

PMID- 16981112
TI  - "Red flag" techniques in Barrett's esophagus: minor additional benefit or a waste
      of time?

PMID- 16981113
TI  - Training facilities in gastrointestinal endoscopy: an animal model as an aid to
      learning endoscopic ultrasound.
AB  - Apart from dedicated fellowships, endoscopic ultrasound (EUS) training comprises
      "informal" methods, including EUS courses and the use of animal models. We have
      tried to determine the usefulness of a "hands-on" experience with a live animal
      model as a teaching strategy for EUS training. In 1997 and 2000 the American
      Society for Gastrointestinal Endoscopy (ASGE) sponsored hands-on EUS workshops
      using a live porcine model and participants in these courses were asked to
      complete a questionnaire about the course (2 years after the 1997 workshop and
      immediately after the 2000 workshop). The main outcome measurements were the
      usefulness and quality of the overall course and of the hands-on component in
      particular, and the effect on EUS practice patterns. Twenty of 38 attendees (53
      %) responded to the survey administered 2 years after the 1997 course: 95 %
      thought the overall course was useful and 85 % valued the hands-on portion; 60 %
      of respondents had either started performing EUS or, if already experienced in
      EUS, had increased the number of EUS examinations and/or the complexity of EUS
      procedures they performed. Of the 34 participants who were at the 2000 ASGE
      course, over 90 % thought that the course enhanced their EUS skills and 88 %
      believed that they would be likely to perform EUS in the future. The study was
      limited in that it did not account for other methods of EUS training that could
      affect EUS practice patterns and also by the fact that not all the 1997 course
      participants responded to the questionnaire. In conclusion, live animal models
      may be a useful adjuctive method for learning EUS skills for the novice or the
      less experienced endosonographer.

PMID- 16981114
TI  - EUS-guided celiac block and neurolysis.
AB  - Abdominal pain related to pancreatic cancer or chronic pancreatitis can be a
      disabling and difficult symptom to treat for patients, their families, and
      physicians. Pharmacologic therapy with nonsteroidal anti-inflammatory drugs is
      usually ineffective. Opiate analgesics may not be well tolerated and can lead to
      dependence. Endoscopic ultrasound-guided celiac plexus block offers a potential
      adjunct treatment for pain control.

PMID- 16981115
TI  - Further evidence to support the safety and efficacy of endoscopic mucosal
      resection for Paris type 0-II, Is and laterally spreading tumors of the
      colorectum in Western cohorts.

PMID- 16981118
TI  - ERCP after a liquid fatty meal: comment.

PMID- 16981119
TI  - Is a second ligation necessary in endoscopic submucosal resection of rectal
      carcinoid tumors?

PMID- 16981120
TI  - Fecal incontinence treated with percutaneous endoscopic cecostomy.

PMID- 16981121
TI  - Endoscopic ultrasound-guided ethanol lavage of a pancreatic fluid collection.

PMID- 16981122
TI  - Direct percutaneous endoscopic jejunostomy tube placement using a fine needle for
      jejunal anchoring.

PMID- 16981123
TI  - Endoscopic removal of a band ligation device from the esophagus.

PMID- 16981124
TI  - Abscess formation in a giant gastrointestinal stromal tumor of the stomach
      following endoscopic biopsy.

PMID- 16981125
TI  - Squamous-cell carcinoma of the duodenum as a rare cause of upper gastrointestinal
      bleeding.

PMID- 16981126
TI  - Esophagitis and anticonvulsant hypersensitivity syndrome.

PMID- 16981127
TI  - Immunoactive polysaccharide-rich fractions from Panax notoginseng.
AB  - Panax notoginseng is a commonly used medicinal plant in south-western China. In a
      previous study, a sequential solubilisation of P. notoginseng high-molecular
      weight (HMW) polymers using phenol-acetic acid-water, hot water, weak and strong
      alkali was performed to determine the structure of the component polysaccharides
      and proteins. The effects of these extracted HMW fractions on the human
      complement system, polymorphonuclear neutrophils (PMN) and peripheral blood
      mononuclear cells (PBMC) are reported here. Fr (1MKOH), which was extracted with
      1 M KOH, showed the strongest complement-fixing activity and priming of reactive
      oxygen species (ROS) production by PMNs, as well as a mitogenic effect. Fr
      (1MKOH) was further fractionated by anion-exchange chromatography followed by gel
      permeation chromatography. 1MD3-G2, the fraction most strongly bound to the DEAE
      anion-exchange column with a molecular weight of 1140 kDa, showed the highest
      complement-fixing activity. It is composed of acidic polysaccharides [including
      glucuronoarabinoxylan (GAX), homogalacturonan (HGA), rhamnogalacturonan I (RG
      I)], neutral polysaccharides (4-galactan and arabinan), and some protein.

PMID- 16981128
TI  - Antimycobacterial activity of geranylated furocoumarins from Tetradium daniellii.
AB  - Seven geranylated furocoumarins were isolated from the fruits of TETRADIUM
      DANIELLII (Benn.) T.G. Hartley (Rutaceae) and tested for their antimycobacterial
      activity against MYCOBACTERIUM FORTUITUM, M. SMEGMATIS and M. PHLEI. They were
      shown to be highly active, with minimal inhibitory concentrations (MICs) ranging
      from 8 to 64 microg/mL. Xanthotoxin and xanthotoxol, representing furocoumarins
      lacking the lipophilic geranyl side chain, were tested similarly and were shown
      to be inactive. Geraniol alone was inactive as well. The antimycobacterial
      activity of the substances was dependent on the position and polarity of the
      geranyl moiety. The compounds were purified using chromatographic methods.
      Structure elucidation was achieved with 1D and 2D NMR experiments.

PMID- 16981129
TI  - New dihydrodibenzoxepins from Bulbophyllum kwangtungense.
AB  - Three new dihydrodibenzoxepins 7,8-dihydro-5-hydroxy-12,13-methylenedioxy-11
      methoxyldibenz[ B,F]oxepin (1), 7,8-dihydro-4-hydroxy-12,13-methylenedioxy-11
      methoxyldibenz[ B,F]oxepin (2), and 7,8-dihydro-3-hydroxy-12,13-methylenedioxy-11
      methoxyldibenz[ B,F]oxepin (3), were isolated from Bulbophyllum kwangtungense
      Schlecht, along with three known compounds, cumulatin (4), densiflorol A (5) and
      plicatol B (6). Their structures were established by a combination of 1D and 2D
      NMR spectroscopic techniques. All new compounds (1-3) and the known compound
      densiflorol A (5) exhibited anti-tumor activities against HeLa and K562 human
      tumor cell lines.

PMID- 16981130
TI  - A ginsenoside metabolite, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol,
      triggers apoptosis in activated rat hepatic stellate cells via caspase-3
      activation.
AB  - We investigated the apoptotic effects of the protopanaxadiol ginsenosides, Rb (1)
      and Rb (2), and their intestinal bacterial metabolite, 20-O-beta-D-glucopyranosyl
      20(S)-protopanaxadiol (M1), and of the protopanaxatriol ginsenoside, Rg (1), and
      its intestinal bacterial metabolite, 20(S)-protopanaxatriol, in activated rat
      hepatic stellate cells (HSCs) transformed by Simian virus 40 (T-HSC/Cl-6). As
      HSCs play a central role in liver fibrosis, agents that selectively induce
      apoptosis of HSCs could be used to treat this disease. Apoptosis was measured
      using cell viability tests, DNA fragmentation analysis, and immunoblot analysis
      of poly(ADP-ribose) polymerase cleavage. M1 (40 microM for 24 h) significantly
      induced apoptosis in activated rat HSCs. M1 induced apoptosis in a dose-dependent
      manner as shown by DNA fragmentation, an increased population of cells in the sub
      G1 phase, and reduced mitochondrial transmembrane potential. M1 induced caspase-3
      activity in a dose- and time-dependent manner. A specific inhibitor of caspase-3
      prevented induction of apoptosis by M1 as shown by DNA fragmentation analysis. It
      is concluded that M1 induces apoptosis in T-HSC/Cl-6 cells via caspase-3
      activation.

PMID- 16981131
TI  - Diarylbutyrolactone lignans from Linum corymbulosum in vitro cultures.
AB  - The arylbutyrolactone lignans (-)-hinokinin, 3,4 : 3',4'-bis(methylenedioxy)-lign
      7( E)-en-9,9'-olide and 3,4 : 3',4'-bis(methylenedioxy)-lign-7( Z)-en-9,9'-olide,
      hitherto unknown for the genus LINUM, were isolated by HPLC from callus cultures
      of LINUM CORYMBULOSUM (Linaceae) and identified by spectroscopic methods.

PMID- 16981132
TI  - An approach to the inheritance of the sesquiterpene chemotypes within Petasites
      hybridus.
AB  - Sesquiterpene esters are the active principle in the medicinal plant Petasites
      hybridus. Two chemotypes, the petasin chemotype and the furanopetasin chemotype,
      are known, but only the first one is suitable for pharmaceutical purposes.
      Experimental crossings were performed within and between plants of both
      chemotypes to study the genetic basis of the occurrence of these sesquiterpenes.
      The chemotype was determined by TLC in extracts of a small piece of rhizome in
      the parent plants and the progenies. A model including the combined action of two
      genes is proposed to explain the inheritance of the chemotypes where the
      furanopetasin chemotype is under recessive genetic control.

PMID- 16981134
TI  - Effect of isoquinoline alkaloids of different structural types on antiplatelet
      aggregation in vitro.
AB  - Forty-one isoquinoline alkaloids were tested for antiplatelet aggregation
      effects. Among them, (-)-discretamine (6), protopine (7), ochotensimine (18), O
      methylarmepavinemethine (23), lindoldhamine (25), isotetrandrine (26),
      thalicarpine (27), papaverine (28), and D-(+)- N-norarmepavine (32) exhibited
      significant inhibitory activity towards adenosine 5'-diphosphate (ADP)-,
      arachidonic acid (AA)-, collagen-, and/or platelet-activating factor (PAF)
      induced platelet aggregation. The results are discussed on the basis of structure
      activity relationships.

PMID- 16981135
TI  - Adenovirus-delivered DKK3/WNT4 and steroidogenesis in primary cultures of
      adrenocortical cells.
AB  - The Wnt family molecules Dickkopf-3 (DKK3) and WNT4 are present at higher
      concentrations in the zona glomerulosa than in the rest of the adrenal cortex. In
      order to study direct effects of these proteins on adrenocortical cell function,
      we created adenoviruses encoding human DKK3 and WNT4. When added to cultured
      human adrenocortical cells, DKK3 inhibited aldosterone and cortisol biosynthesis,
      either alone or together with cyclic AMP. WNT4 increased steroidogenesis when
      added alone but decreased it in the presence of cyclic AMP. A control adenovirus
      encoding GFP had no effect. RNA was prepared from cultured cells and was assayed
      by real-time PCR. CYP11A1 (cholesterol side-chain cleavage enzyme), HSD3B2 (3beta
      hydroxysteroid dehydrogenase type II), CYP17 (17 alpha-hydroxylase), CYP21 (21
      hydroxylase) and CYP11B1 (11 beta-hydroxylase) mRNAs were all increased by cyclic
      AMP, whereas CYP11B2 (aldosterone synthase) was unaffected. DKK3 decreased cyclic
      AMP-stimulated CYP17. WNT4 increased both CYP17 and CYP21 in the absence of
      cyclic AMP. Both DKK3 and WNT4 increased the level of CYP11B2. These data show
      that these Wnt signaling molecules have multiple actions on steroidogenesis in
      adrenocortical cells, including effects on overall steroidogenesis (aldosterone
      and cortisol biosynthesis) and distinct effects on steroidogenic enzyme mRNA
      levels. The co-localization of DKK3 and WNT4 in the glomerulosa and their
      stimulation of CYP11B2 imply an action on glomerulosa-specific function.

PMID- 16981136
TI  - Effect of growth hormone in an experimental model of protein hypercatabolism
      induced by glucocorticoids.
AB  - OBJECTIVE: The aims of the study were to evaluate whether growth hormone could be
      beneficial in a model of hypercatabolism induced by glucocorticoids and to
      examine its effects on ACTH, corticosterone and IGF-1 levels. The effects of
      growth hormone on the expression of both glucocorticoid receptor and tyrosine
      aminotransferase were also evaluated. METHODS: Fifty Wistar rats were divided
      into five groups and treated as follows: (A) daily subcutaneous injection of
      growth hormone (4.8 IU/kg/day) and oral placebo, (B) daily injection of placebo
      and oral dexamethasone (3 mg/kg/day), (C) daily injection of growth hormone and
      oral dexamethasone, (D) daily injection of placebo and oral placebo, and (E) no
      treatment. The animals were decapitated seven days after initiating treatment.
      RESULTS: Growth hormone did not modify the weight loss induced by dexamethasone.
      Glucocorticoid receptor expression was significantly lower in group A than in
      group E. An increase in tyrosine aminotransferase was observed in group C.
      CONCLUSION: Growth hormone did not exert any beneficial effect in this model of
      hypercatabolism. Growth hormone decreased glucocorticoid receptor expression.
      This fact could explain its beneficial effect when protein hypercatabolism is not
      the predominant phenomenon. Growth hormone induced the hyperexpression of
      tyrosine aminotransferase, thus suggesting an amplifying effect on the
      glucocorticoid action.

PMID- 16981137
TI  - Phosphatidylinositol 3-kinase/Akt plays a part in tumor necrosis factor-alpha
      induced interleukin-6 synthesis in osteoblasts.
AB  - We previously showed that tumor necrosis factor-alpha (TNF-alpha) stimulates
      synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, via p44/p42
      mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the
      present study, we investigated whether phosphatidylinositol 3-kinase (PI3
      kinase)/protein kinase B (Akt) is involved in TNF-alpha-stimulated IL-6 synthesis
      in MC3T3-E1 cells. TNF-alpha induced the phosphorylation of Akt depending upon
      time. Akt inhibitor, 1L-6-hydroxymethyl-CHIRO-inositol 2-( R)-2- O-methyl-3-O
      octadecylcarbonate, significantly suppressed the TNF-alpha-stimulated IL-6
      synthesis, but the inhibitory effect was partial. The phosphorylation of Akt
      induced by TNF-alpha was markedly attenuated by LY294002 and wortmannin,
      inhibitors of PI3-kinase. Wortmannin and LY294002 significantly reduce the TNF
      alpha-induced IL-6 synthesis. On the contrary, the suppressive effects of Akt
      inhibitor, wortmannin or LY294002 on TNF-alpha-induced phosphorylation of p44/p42
      MAP kinase were minor. PD98059, a specific inhibitor of MEK, had little effect on
      the TNF-alpha-induced phosphorylation of Akt. A combination of Akt inhibitor and
      PD98059 suppressed the TNF-alpha-induced IL-6 synthesis in an additive manner.
      These results strongly suggest that PI3-kinase/Akt plays a role in the TNF-alpha
      stimulated IL-6 synthesis mainly independent of p44/p42 MAP kinase in
      osteoblasts.

PMID- 16981138
TI  - Tumor necrosis factor alpha induces the expression of the nuclear protein p8 via
      a novel NF kappaB binding site within the promoter.
AB  - p8 is a widely expressed HMG-I/Y-like transcription factor which is involved in
      regulating cell proliferation and tissue stress. Several studies describe a
      strong upregulation of p8 expression during inflammatory processes like
      pancreatitis and LPS-induced sepsis. Here we demonstrate that TNFalpha, which is
      an important inducer of innate defence against gram-negative bacteria,
      significantly stimulates p8 protein production in H4IIE rat hepatoma cells within
      2 hours. Since a putative NF kappaB motif has been described, we further tested
      whether TNFalpha stimulates p8 expression via activation of NF kappaB. We
      characterized the TNFalpha-induced binding of NF kappaB to this motif. We show
      that the TNFalpha-induced NF kappaB pathway contributes to the induction of p8
      during pancreatitis and LPS-induced inflammation.

PMID- 16981139
TI  - Oxidative stress in young Zucker rats with impaired glucose tolerance is
      diminished by acarbose.
AB  - AIMS/HYPOTHESIS: There is evidence that acarbose reduces the risk for development
      of diabetes and cardiovascular complications. The mechanism underlying the
      vasculoprotective effect is however not known. We hypothesized that
      vasculoprotection observed by acarbose may be the consequence of a diminished
      generation of oxidative stress. METHODS: Lean and obese Zucker rats received a
      diet containing 10% sucrose for 7 days. A part of the rats was treated with
      acarbose (15 mg/kg/day in chow). Blood glucose, plasma insulin, lipid peroxides,
      and as a more specific marker of oxidative stress, 8-isoprostanes, were analyzed.
      As cellular markers of oxidative stress we determined the activities of
      mitochondrial aconitase and NADPH-oxidase in aorta, heart, and kidney. In
      addition, poly(ADP-ribose) polymerase activity (PARP) was measured in aorta.
      RESULTS: Sucrose feeding of obese Zucker rats resulted in increased blood glucose
      levels, plasma insulin, lipid peroxides and 8-isoprostanes. Mitochondrial
      aconitase was reduced; the activities of NAPDH-oxidase and PARP were enhanced.
      Treatment of obese Zucker rats with acarbose largely prevented these changes,
      whereas it had no effect in lean sucrose fed rats. CONCLUSION: Specifically in
      obese Zucker rats sucrose feeding is associated with an increased oxidative
      stress. The data provide IN VIVO evidence that mitochondria play a role in the
      generation of reactive oxygen species (ROS) in insulin resistant, hyperglycaemic
      states. Activation of PARP by ROS may be an important mediator of vascular
      dysfunction in insulin resistance. Treatment with acarbose is helpful to prevent
      the increase in oxidative stress and vascular dysfunction induced by
      hyperglycemia.

PMID- 16981140
TI  - Serum lipoprotein(a) dynamics before/after menopause and long-term effects of
      hormone replacement therapy on lipoprotein(a) levels in middle-aged and older
      Japanese women.
AB  - AIM: To assess lipoprotein(a) Lp(a) dynamics before and after menopause and to
      examine long-term changes during hormone replacement therapy (HRT) in middle-aged
      and older Japanese women. METHODS: (1) Serum total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, and Lp(a)
      concentrations of 526 patients were compared. The patients were divided into 3
      groups on the basis of menopausal status (premenopause, perimenopause,
      postmenopause). (2) Serum markers of lipid metabolism were measured at baseline
      and at 6-month intervals in 161 postmenopausal women who continuously received
      HRT with conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA)
      for 4 years. (3) Changes in serum concentrations of markers were compared among
      120 women with hypercholesterolemia who were randomly assigned to receive HRT
      (CEE plus MPA, or transdermal estradiol plus MPA) or pravastatin. RESULTS: (1)
      Lp(a) concentrations were significantly higher in the postmenopausal women than
      in the premenopausal or perimenopausal women. (2) The mean Lp(a) concentration
      after 6 months of HRT decreased by about 19%, and similar levels were maintained
      for 4 years (3). The mean Lp(a) concentration after 6 months of HRT decreased by
      19.9% in the CEE plus MPA group, but did not change significantly in the
      transdermal estradiol plus MPA group or the pravastatin group. CONCLUSION: Our
      results suggest that HRT with CEE plus MPA is useful for the management of
      elevated serum Lp(a) concentrations in middle-aged and older women. However,
      follow-up studies are needed to determine whether this finding is related to the
      future prevention of coronary heart disease events.

PMID- 16981141
TI  - Prolactin, cortisol secretion and thyroid function in patients with stroke of
      mild severity.
AB  - Different attempts were made to identify the variables that may be involved in
      the clinical course of cerebrovascular ischemia. In the case of stroke with mild
      severity (SMS), the clinical significance of neuroendocrine changes as well as of
      post-stroke depression (PSD) remains unknown. We therefore evaluated the presence
      of neuroendocrine changes in the acute and post-acute phase of SMS, and their
      potential role during convalescence. Serum cortisol, T4, T3, FT4, FT3, TSH and
      PRL levels were measured in 17 euthyroid patients with stroke on admission (day
      1), following morning (day 2), 7 days and 3 months later. TSH and PRL secretion
      after TRH test were measured. Stroke severity on admission was determined by
      Scandinavian Stroke Scale (SSS). Montgomery-Asberg Depression Rating Scale
      (Madrs) was used for assessment of post-stroke depression. On admission, TSH and
      T3, were within normal limits and were greater compared to values on day 2. Lower
      basal TSH and decreased TSH response to TRH on day 2, were associated with stroke
      of greater severity. Delta-PRL after TRH on day 2 was higher in patients who
      develop PSD. Changes in serum thyroid hormones in SMS, reflects those of non
      thyroidal illness. A mild stimulation of hypothalamic-pituitary-adrenal axis was
      detected. We provide evidence that PRL response to TRH, in the acute phase of
      stroke may be used as an index for early detection of PSD.

PMID- 16981142
TI  - Insertion/deletion polymorphism on ACE gene is associated with endothelial
      dysfunction in young patients with hypertension.
AB  - Endothelial dysfunction, insulin resistance (IR) and genetic predispositions are
      important risk factors of hypertension. Aim of our study was to test the
      hypothesis, whether insertion/deletion (I/D) polymorphism on the angiotensin
      converting enzyme (ACE) gene and M235T polymorphism on angiotesinogen gene (AGT)
      correlates with parameters of insulin sensitivity and plasminogen activator
      inhibitor (PAI-1) levels in newly diagnosed hypertensive patients as compared
      with normotensive controls. Blood pressure (BP), fasting plasma glucose, insulin,
      epinephrine, norepinephrine and PAI-1 concentrations were determined in 30 male
      patients with hypertension grade 1 (HT) and in 31 matched healthy subjects (NT).
      Insulin resistance was estimated using IR HOMA formula. Patients with HT had
      increased levels of PAI-1, norepinephrine, fasting plasma insulin levels, IR HOMA
      (p<0.001) compared to controls. Subjects (HT and NT) with DD and ID genotype had
      a significantly higher systolic BP (p<0.05) and PAI-1 compared to those with II
      genotype. Homozygous subjects 235T had a higher systolic BP and higher levels of
      epinephrine and norepinephrine than heterozygous or homozygous M235 (p<0.05). In
      conclusion, no association was found between M235T polymorphism and insulin
      resistance or PAI-1 levels, but results indicate relationship between I/D
      polymorphism of the ACE gene and plasma PAI-1 levels in the early stage of
      hypertension.

PMID- 16981143
TI  - A study to determine if acute maternal and fetal hyperglycemia/insulinemia
      induces leptin production during pregnancy.
AB  - BACKGROUND: In pregnant primates, the effect of post-prandial hyperglycemic or
      insulinemic states on leptin production is not known. Our goal was to conduct a
      controlled study using an established pregnant baboon model ( PAPIO ANUBIS) to
      determine whether acute glucose changes would have an effect on maternal or fetal
      plasma leptin levels. METHODS: Two animals were operated on at 138 and 140 days
      of gestation (term approximately 184 days) by placing 4 cannulae in the maternal
      aorta, inferior vena cava, fetal carotid artery, and the amniotic cavity. At 145
      and 150 days, glucose infusions were started via the maternal femoral vein.
      Animal 1 received 7.5 gm of glucose over a 2-hour period at 145 th day. Animal 2
      received 20 gm of glucose over a 1-hour period at 150th day. Both animals
      remained ad libitum throughout the experiments. Maternal and fetal blood samples
      were obtained from the arterial lines before the glucose infusion and at half
      hour intervals to include 30 minutes post-infusion. RESULTS: Significant changes
      from baseline concentrations were observed for maternal and fetal glucose and
      insulin concentrations in response to both glucose challenges. Maternal and fetal
      plasma leptin concentrations did not correlate with glucose or insulin changes.
      CONCLUSION: This preliminary study demonstrated that in primates, acute changes
      in circulating maternal or fetal glucose or insulin concentration do not affect
      maternal or fetal plasma leptin concentrations. These results suggest that
      alterations in leptin secretion by the maternal-placental-fetal unit may only
      occur in pathological states.

PMID- 16981144
TI  - The insertion/deletion polymorphism in the angiotensin-converting enzyme gene and
      hypoglycemia awareness in patients with type 1 diabetes.
AB  - Impaired hypoglycemia awareness affects approximately 25% of all patients with
      type 1 diabetes (T1DM). Duration of diabetes and tight glycemic control represent
      main risk factors of impaired hypoglycemia awareness. However, even among
      patients with good glycemic control and longstanding T1DM, awareness of
      hypoglycemia may be intact. Genetic factors might explain some of this remaining
      variability. Recently, the insertion/deletion ( I/ D) polymorphism in angiotensin
      converting enzyme gene ( ACE) was shown to be associated with significantly
      higher risk of hypoglycemic events in subjects with T1DM. Here, we studied the
      effects of genetic polymorphisms in the ACE on impaired hypoglycemia awareness in
      231 Caucasian T1DM patients. Hypoglycemia awareness status was determined using
      standardized questionnaires (Clarke et al. and Edinburgh Hypoglycemia Scale). ACE
      I/ D genotype was determined by PCR amplification of the respective fragments
      from intron 16 of the ACE and size fractionation (I allele frequency=0.49; P=0.74
      for Hardy-Weinberg equilibrium). In the logistic regression analysis, significant
      risk factors of impaired hypoglycemia awareness were duration of diabetes, C
      peptide and HbA (1c) (all P<0.01). However, no significant effect of the I/ D
      polymorphism on impaired hypoglycemia awareness was observed with and without
      adjustment for age, diabetes duration, C-peptide and HbA (1c). Even though the
      study provides a relatively large dataset, it is possible that small differences
      may have been missed.

PMID- 16981145
TI  - Diurnal variation in insulin-stimulated systemic glucose and amino acid
      utilization in pigs fed with identical meals at 12-hour intervals.
AB  - The diurnal variation in insulin-stimulated systemic glucose and amino acid
      utilization was investigated in eleven pigs of approximately 40 kg. Pigs were fed
      isoenergetic/isoproteinic diets (366 kJ/kg BW (0.75) per meal) in two daily
      rations (06:00 and 18:00 h). After a 3-week habituation period, hyperinsulinemic
      euglycemic euaminoacidemic clamp studies (by intra-portal insulin, glucose and
      amino acids infusion and arterial blood sampling) were performed starting at
      06:00 or 18:00 h (while skipping the meal), using a cross-over within-animal
      design. Basal (preclamp) plasma concentrations of insulin, glucose, lactate,
      individual amino acids and urea were similar in the morning compared to the
      evening. Insulin-stimulated ( approximately 4-fold increase over basal) systemic
      glucose utilization was similar (17.6+/-1.4 and 18.9+/-1.8 mg x kg (-1) x min (
      1)) but amino acid utilization was 19% greater in the morning VS. the evening
      (2.37+/-0.21 VS. 1.99+/-0.15 mg x kg (-1) x min (-1), p<0.05), respectively.
      Insulin-stimulated plasma lactate concentrations remained constant in the morning
      (0.77+/-0.06 to 0.71+/-0.04 mmol x l (-1)) but declined in the evening (0.89+/
      0.09 to 0.65+/-0.06 mmol x l (-1), p<0.05). By contrast, insulin-stimulated
      plasma urea concentrations declined in the morning (2.48+/-0.11 to 2.03+/-0.10
      mmol x l (-1), p<0.005) but remained constant in the evening (2.18+/-0.14 to
      2.12+/-0.12 mmol x l (-1)). In conclusion, pigs fed identical meals at 12-hour
      intervals follow a clear diurnal biorhythm in protein anabolism, with greater
      insulin-stimulated systemic amino acid utilization and lower plasma urea response
      in the morning compared to the evening.

PMID- 16981146
TI  - The PPAR gamma agonist troglitazone induces musclin mRNA expression in human
      myotubes.

PMID- 16981153
TI  - [Do we need a "new" form of child rearing?].

PMID- 16981154
TI  - [Factors influencing juvenile alcohol consumption: the role of gene-environment
      interactions].
AB  - INTRODUCTION: Excessive alcohol consumption in youth increases the risk of
      subsequent alcohol use disorders. Despite the recognition of genetic and
      environmental factors, an appropriate aetiological model is needed to take
      adequate preventative steps. This is in part due to the complex interactions
      between genotype and environment. In this article we review research on factors
      determining alcohol use by adolescents and on the development of an unifying
      model. METHOD: The data bank Medline Advanced was searched for topical articles
      that were then checked for relevance and sorted according to genetic factors,
      environmental factors, and their interactions. RESULTS: Many factors, alone and
      in combination with others, influence juvenile alcohol consumption. Each single
      variable, however, can explain only a small part of the variation in consumption
      behaviour. CONCLUSION: The manifold possibilities of interactions between these
      factors become clear. There is a strong need for comprehensive models of juvenile
      alcohol use and the integration of current results into these models.

PMID- 16981155
TI  - [Neuroimaging data of ADHD, tic-disorder and obsessive-compulsive-disorder in
      children and adolescents].
AB  - ADHD, Tic Disorder, Tourette's Syndrome, and Obsessive-Compulsive Disorder are
      all characterised by an impairment of executive functioning and often occur
      together. There are thus indications of a similar neurobiological basis. This
      review presents an overview of neuroimaging studies of these disorders in
      childhood and adolescence, focusing thereby on magnet resonance imaging data.
      Studies provide concurring data about structural changes in the basal ganglia and
      the prefrontal cortex, and abnormal activation in the fronto-striatal circuitry
      in patients as compared to healthy controls. ADHD and Tourette's Syndrome are
      both associated with prefrontal aberrations. However, variances in Tourette's
      Syndrome are less pronounced, which might be due to compensation mechanisms. ADHD
      children show small, but more global, morphological alterations in the cortex and
      cerebellum, while Tourette's Syndrome seems to be linked additionally to
      differences in the occipital cortex. Furthermore, structural and functional data
      for obsessive-compulsive disorder indicate aberrations in the amygdala and
      thalamus, and functional changes in the orbito-frontal cortex. By comparison,
      findings in children with ADHD point towards abnormal activity in the ventral
      prefrontal cortex. To summarise, the data display an impairment of cortico
      striato-thalamic circuits which appears to be associated with dysfunctioning
      motor inhibition, and impulsive behaviour and objectionable thoughts. Since the
      majority of the studies reviewed are characterised by small and heterogeneous
      samples, and since the studies differ in their methods, comparability is limited
      and general conclusions can not be drawn.

PMID- 16981156
TI  - [Attention deficit/hyperactivity disorders among three-to-six-year-olds treated
      in medical practices--a national survey].
AB  - OBJECTIVE: The aim of the study is to calculate prevalence rates of symptoms and
      diagnoses of Attention Deficit-/Hyperactivity Disorders (ADHD) in preschoolers,
      and to assess functional impairment as well as comorbid symptoms by means of
      parents and teacher symptom checklists. METHOD: N = 708 kindergarten- and
      preschool-children were recruited nationwide by pediatricians or child and
      adolescent psychiatrists. The U8/U9 sample (n = 521 children) was assessed during
      a routine pediatric screening. The clinical sample consisted of n = 187 children
      who were rated as having ADHD problems by the physician. The children were
      assessed by age-adapted ADHD Symptom-Checklists (Fremdbeurteilungsbogen fur
      Aufmerksamkeitsdefizit-/Hyperaktivitatsstorungen im Vorschulalter FBB-ADHS-V)
      rated by parents and teachers. Additionally, the physicians rated ADHD symptoms
      and comorbid symptoms. RESULTS: Based on diagnosis criteria of DSM-IV and the
      parental ratings in U8/U9, 11.3% of the children fulfilled the criteria for one
      of the three ADHD diagnoses (ICD 10: 3.8%). The prevalence rate was lower in
      teacher ratings (6.6%) (ICD 10: 1.5%), and in both the parent and teacher ratings
      4.2% of the children fulfilled the DSM-IV criteria for ADHD (ICD 10: 1.2%).
      Higher prevalence rates and comorbidities were found in the clinical sample. The
      need for professional help (counseling/treatment) is much higher than the
      treatment the parents and children actually received. CONCLUSION: International
      prevalence rates can be applied. Despite methodological restrictions, such as a
      lack of representativeness and possible pre-selection effects, this study
      demonstrates the relevance of prevention and intervention programmes.

PMID- 16981157
TI  - [Consumer satisfaction trajectories of adolescents during in-patient psychiatric
      treatment].
AB  - OBJECTIVE: Patient satisfaction with in-patient treatment and other aspects of
      process quality is usually examined cross-sectionally (e.g. at discharge).
      Therefore, the knowledge about changes in patient satisfaction and related
      issues, such as participation and motivation during the treatment period, is
      limited. This study describes the development of a questionnaire covering these
      topics and the course and variability in these domains for different subgroups.
      METHOD: The study group comprises 88 adolescents (48 females, 40 males; aged 13
      to 18 years) who delivered altogether 1,003 data points (median per person is 8).
      The questionnaire consisted of 16 items that were administered to them by
      computer twice a week at adolescent wards in two psychiatric departments.
      Statistical analysis was done using hierarchical linear modeling (growth curve
      models), which is well suited for the analysis of data with different numbers of
      assessment points and missing data. RESULTS: Psychometric properties of the
      questions were good. The trajectories for all items are very heterogeneous with
      regard to the level.. The trends (slope of the growth curves) are around 0 in
      general satisfaction, i.e. the adolescents stay on their different levels during
      the treatment period. Concerning participation, however, there are diverging
      trends, in particular between the two departments, which may reflect the
      difference in the treatment experience of the teams, whereas age, gender and
      diagnosis (internalizing vs. externalizing) play a minor role. CONCLUSION:
      Evaluation of process characteristics has turned out to be feasible in clinical
      routine and promising for further insights into process quality.

PMID- 16981158
TI  - [Bibliotherapy as a self-help program for parents of children with externalizing
      problem behavior].
AB  - OBJECTIVES: Externalizing problem behaviour is one of the most frequent and most
      stable behavioural disorders of childhood and adolescence. The development of
      applicable alternatives to expensive and restrictedly available treatments
      becomes increasingly necessary. This pilot study tested bibliotherapy in the form
      of a manual-assisted self-help programme under minimum contact conditions for
      parents of children with externalizing problem behaviour. METHOD: A total of 21
      children, aged 6 to 15 years and diagnosed with Attention-Deficit/Hyperactivity
      Disorder (ADHD) and/or an Oppositional Defiant Disorder, were recruited from an
      outpatient population. The bibliotherapy lasted 10 weeks and consisted of working
      through a self-help book for parents (Wackelpeter und Trotzkopf). Initial
      clinical interviews and pre- and post-treatment evaluations were included, as
      well as short weekly telephone contacts (approx. 20 min. per contact) with the
      parents. RESULTS: The children's externalizing behaviour was significantly
      reduced during the intervention. The parenting skills were strengthened. The
      satisfaction of the parents with the program was high. Fewer than 20% of the
      parents indicated a need for an additional intensive behavioural outpatient
      treatment at the end of the intervention. CONCLUSIONS: Bibliotherapy may be an
      applicable and effective treatment alternative for children with disruptive
      behaviour disorders, at least in families with the resources necessary for this
      kind of intervention. The results have to be replicated within randomized control
      group trials.

PMID- 16981162
TI  - [Brainstem auditory evoked potentials and vertex potentials in 5-year-old
      children with defective articulation of the phonemes /l/, /r/, /rr/ and /s/].
AB  - AIMS: In children with articulatory defects it is important to evaluate the
      central auditory level. We compared the results of the interwave intervals of
      brainstem auditory evoked potentials (BAEP) at 80 dB SPL (sound pressure level)
      and the latencies of the waves of long latency auditory evoked potentials (LLAEP)
      (vertex) in 5-year-old children with articulatory defects for /l/, /r/, /rr/ and
      /s/, and in controls. SUBJECTS AND METHODS: Fifty cases of 5-year-old children of
      both sexes were evaluated; 25 had articulatory defects and 25 with no
      articulatory defects were used as controls. Melgar's articulation test was
      applied to both groups. The following aspects were considered in the two groups:
      normal bilateral audition by means of tone audiometry, tympanometry and the
      revised Wechsler Intelligence Scale for preschool and primary school children,
      which were normal; there was no history of neurological damage. Interwave
      intervals for waves I-III, I-V and III-V of the BAEP and the latencies of the
      LLAEP (vertex) were evaluated. RESULTS: Data were analysed using SPSS 12, and
      descriptive statistics and Student's t test were carried out to appraise the
      differences between the two groups. No differences were found between the control
      group and the study group. CONCLUSIONS: It is important to determine whether
      children with articulatory defects have alterations in the auditory receptor or
      in their central auditory function. It can be concluded that the variables
      analysed in the two groups behave in the same way; no significant differences
      were found, which suggests that neither the auditory receptor nor the central
      auditory function are affected in the study group. Further studies are to be
      conducted to investigate the meaning of the difference in central nervous
      conduction between the two afferences in the study group.

PMID- 16981161
TI  - [Interferon-beta response in multiple sclerosis associated with pre-treatment
      disability].
AB  - AIM: To study pre-treatment clinical features and influence of neutralising
      antibodies (NABs) in clinical response to interferon-beta (IFNB). PATIENTS AND
      METHODS: We analysed clinical characteristics and NABs to IFNB in 96 multiple
      sclerosis patients treated with IFNB. Clinical response was established by
      clinical criteria: = 1 relapse or an increase = 0.5 or 1 point in the Expanded
      Disability Status Scale (EDSS) score after one year of treatment compared with
      the year prior to IFNB therapy. RESULTS: Baseline clinical characteristics were
      similar for responders and non-responders, except for a significantly higher
      baseline mean EDSS score in non-responders. Time-to-first-relapse was longer and
      the number of patients relapse-free was higher for NAB-negative patients, but we
      were unable to show an association with the disability status, probably due to
      sample size. CONCLUSIONS: Response to IFNB was significantly associated with pre
      treatment disability measured by the EDSS. The presence of NABs to IFNB presented
      a delayed negative effect for relapses.

PMID- 16981163
TI  - [Benign paroxysmal torticollis. Our experience gained over a 15-year period].
AB  - INTRODUCTION: Benign paroxysmal torticollis (BPT) is characterised by recurring
      episodes of lateral bending of the neck, occasionally accompanied by vegetative
      symptoms, ataxia or an abnormal position of the trunk, with a tendency to
      disappear spontaneously after some months or years, and with no alterations
      between episodes. AIM: To analyse the clinical and developmental characteristics
      of the cases evaluated by the Neuropaediatric Service at our hospital that were
      classified as BPT. PATIENTS AND METHODS: We reviewed the history of the patients
      with BPT included in the Neuropaediatric Service database over a 15-year period.
      Patients who were not following any kind of control were contacted by telephone.
      RESULTS: We found 13 BPT patients with typical criteria, and 4 others with
      possible BPT (p-BPT), because they had had an isolated episode of torticollis.
      Neuroimaging was carried out in nine children (69.2%) from the BPT group: this
      included only transfontanellar ultrasound recording (TF USR) in six cases, TF USR
      and computerised axial tomography (CAT) in one child, only a CAT scan in one
      case, and CAT and magnetic resonance imaging in another. Neuroimaging was
      performed in all the cases of p-BPT: CAT scans were carried out in two cases and
      TF USR was used in two others. CONCLUSIONS: Atypical cases can be excluded by
      establishing a diagnosis of BPT with strict criteria. Since no biological markers
      are available, the diagnosis must be based on the clinical pattern and course
      and, in some cases, complementary examinations have to be performed to preclude
      other pathologies. When a child is diagnosed with BPT, the family needs to be
      reassured and told that it is a benign process with a tendency to disappear
      spontaneously.

PMID- 16981164
TI  - [Pyruvate dehydrogenase deficit associated to the C515T mutation in exon 6 of the
      E1alpha gene].
AB  - INTRODUCTION: Pyruvate dehydrogenase (PDH) deficiency constitutes the most
      frequent metabolic origin of congenital lactic acidosis and is also responsible
      for a less usual form, found exclusively in females, which leads to a dysmorphic
      syndrome accompanied by severe cerebral malformations. The most common defect
      affects fraction E1alpha (gene Xp22.1-22.2). AIM: To report the case of a young
      female with PDH deficiency, dysmorphic syndrome, cerebral deformations and an
      unidentified mutation in the corresponding gene. CASE REPORT: An 8-month-old
      female with microcephaly, a narrow forehead, nasal hypoplasia, anteverted
      nostrils, thin lips, axial hypotonia, epileptic seizures and an umbilical hernia.
      Magnetic resonance imaging of the brain revealed intense supra- and
      infratentorial cortico-subcortical atrophy, ventricular dilatation and agenesis
      of the corpus callosum. Lactic and pyruvic acid concentrations were high both in
      blood and in cerebrospinal fluid (CSF), and the level of alanine was high in CSF.
      Muscular histology results were normal. PDH complex activity in fibroblasts and
      in muscle tissue, as well as that of the mitochondrial respiratory chain
      complexes in muscle homogenate, were found to be normal. A molecular genetic
      study of the gene for PDHE1alpha, both in formed elements in the blood and in
      fibroblasts, showed a C > T change in nucleotide 515 (C515T) of exon 6, which
      causes a P172L change in the protein. A study of 108 controls ruled out the
      possibility of a polymorphism. The parents did not have the mutation.
      CONCLUSIONS: The C515T mutation of exon 6 of the gene for PDH E1alpha is
      described. Normal activity of the PDH complex in fibroblasts and in muscle tissue
      does not exclude this condition.

PMID- 16981165
TI  - [Unilateral facial and cerebral hyperplasia associated with neurofibromatosis
      type 1. Report of four patients].
AB  - INTRODUCTION: Plexiform neurofibroma in any location is one of the commonest
      complications associated with neurofibromatosis type 1 (NF1). Plexiform
      neurofibroma of the upper eyelid and orbit is usually associated with ipsilateral
      hemifacial hyperplasia. We present four patients with NF1 and plexiform
      neurofibroma of the eyelid and orbit associated with hemifacial hyperplasia, who
      also showed hyperplasia of the unilateral cerebral hemisphere. CASE REPORTS:
      There are four patients, three females and one male, who consulted because of NF1
      with plexiform neurofibroma of upper eyelid and hemifacial hyperplasia. Upper
      eyelid involvement was observed since birth and progressed during the first years
      of life. The patients showed normal neurological and mental development without
      motor or cerebellar disorders. Magnetic resonance studies demonstrated the
      asymmetric hyperplasia of the ipsilateral hemisphere in all four cases and of the
      cerebellar hemisphere in one case. The degree of hemispheric hyperplasia was
      related to the size and extension of the plexiform neurofibroma, as well as to
      the severity of the hemifacial hyperplasia. In our case which had the plexiform
      neurofibroma extended to the neck and the upper thorax, the hyperplasia not only
      affected the cerebral hemisphere but also the ipsilateral cerebellar hemisphere.
      All parts of the hemisphere showed increased size. The cortex of the entire
      hemisphere showed normal differentiation of the subcortical white matter.
      CONCLUSION: NF1 appears to be related with facial and cerebral ipsilateral
      hemihyperplasia. The relation between the size and extension of the orbital,
      eyelid and facial plexiform neurofibroma and the degree of asymmetry of the
      hemispheric hyperplasia suggest that different influences of a still unknown
      agent, possibly a gene, obviously related to NF1, causes both the intracranial
      and extracranial abnormalities.

PMID- 16981166
TI  - [Pharmacogenomics in neuro-oncology].
AB  - INTRODUCTION AND DEVELOPMENT: Chemotherapy protocols for treatment of brain
      tumors use toxic molecules for killing cancer cells in a similar way that
      protocols for treating other cancers. Therefore, secondary effects and poor
      response are the major handicaps. Technological developments based on
      pharmacogenomics and pharmacoproteomics will predict response and toxicity giving
      rise to a personalized medicine. However, there are only few studies that
      correlate chemotherapeutical molecules for brain tumor treatment and prediction
      of response and toxicity. CONCLUSIONS: The development of new technologies based
      on high-density microarrays allows the progressive identification of genes whose
      presence will predict the efficacy of therapeutic protocols. Once identified,
      specific equipments based on low-density arrays will detect exclusively in an
      easy and fast way the presence of genes in order to predict patient's response
      and avoid toxicity. Other more sophisticated techniques at present still at an
      experimental step based on proteomics as MALDI (Matrix-Assisted Laser Desorption
      Ionization) and SELDI (Surface-Enhanced Laser Desorption Ionization) will allow
      the identification of proteins that could predict response and toxicity.

PMID- 16981167
TI  - [Giant intracranial aneurysms].
AB  - AIM: Terminology, concept, pathology and phisiopathology, clinical presentation,
      imaging diagnosis and treatment of the giant intracranial aneurysms are reviewed.
      DEVELOPMENT: Saccular, fusiform, dissecting and serpentine giant aneurysms are
      discussed. Giant saccular aneurysms are developed from small regular congenital
      lesions growing far away of their critical rupture size due to the reinforcement
      of their wall. Fusiform and dissecting aneurysms are formed after a wide rupture
      of some of their wall layers and, therefore, both of them are considered to have
      some similarities. Finally, serpentine aneurysms are rare lesions and their
      growing mechanism is still under discussion. CONCLUSION: Any type of giant
      aneurysm represents a great deal for the neurosurgical management.

PMID- 16981168
TI  - [Creation and standardized longitudinal follow-up of a cohort of patients with de
      novo Parkinson's disease: the VIP project].
AB  - INTRODUCTION: Parkinson's disease (PD) is a quite heterogeneous disorder, thus
      difficulting the interpretation of transversal studies. Patients' registries and
      longitudinal studies can be considered as a priority in order to understand many
      still unknown aspects of the disease. AIM: To create and follow in a longitudinal
      way a cohort of 300 patients with de novo PD who will be assessed and treated in
      a uniform way. The end-point of the project will be the donation of the brain.
      DEVELOPMENT: This is a non-hypothesis driven project which immediate steps are:
      a) Inclusion of de novo PD patients; b) Application of a protocol of evaluations
      and treatment recommendations; c) Obtaining and maintenance of biological
      samples; d) Elaboration of a data base to be released on the net; e) Design and
      start of different studies to be performed simultaneously; and f) Brain donation.
      The study will be carried out by the Consorcio Parkinson across the country.
      Retrospective and prospective studies to be addressed in the future are of quite
      diverse nature, from clinical to molecular.

PMID- 16981169
TI  - [Peroneal muscular atrophy secondary to a herniated dorsal disc].

PMID- 16981170
TI  - [Functional independence measure for the evaluation of hemiplegic patients
      disabilities].

PMID- 16981171
TI  - [Neurologic disorders associated with acute intermittent porphyria].

PMID- 16981172
TI  - [Brucellar polyradiculoneuropathy with axonal involvement].

PMID- 16981173
TI  - [Kainate-type glutamate receptors and epilepsy].

PMID- 16981175
TI  - [Vasomotor reactivity and Alzheimer's disease].

PMID- 16981176
TI  - Quantifying the treatment effect explained by markers in the presence of
      measurement error.
AB  - Surrogate markers or intermediate markers are important in identifying subjects
      with high risk of a serious disease or for monitoring disease progression of a
      subject on treatment. Quantifying the proportion of treatment effect (PTE)
      explained by markers has been studied extensively. Due to reasons such as
      biological variation, limited machine precision, etc. markers are generally
      measured with error. The estimated PTE ignoring the measurement error could be
      biased, which may lead to incorrect conclusions. In this article, we adjust for
      the measurement error using regression calibration to construct a less biased
      estimator of excess relative odds, a quantity to measure the treatment effect
      explained by markers. The method is applied to data from a clinical study in
      osteoporosis.

PMID- 16981177
TI  - A comparison of adaptive allocation rules for group-sequential binary response
      clinical trials.
AB  - In clinical trials to compare two or more treatments with dichotomous responses,
      group-sequential designs may reduce the total number of patients involved in the
      trial and response-adaptive designs may result in fewer patients being assigned
      to the inferior treatments. In this paper, we combine group-sequential and
      response-adaptive designs, extending recent work on sample size re-estimation in
      trials to compare two treatments with normally distributed responses, to
      analogous binary response trials. We consider the use of two parameters of
      interest in the group-sequential design, the log odds ratio and the simple
      difference between the probabilities of success. In terms of the adaptive
      sampling rules, we study two urn models, the drop-the-loser rule and the
      randomized Polya urn rule, and compare their properties with those of two
      sequential maximum likelihood estimation rules, which minimize the expected
      number of treatment failures. We investigate two ways in which adaptive urn
      designs can be used in conjunction with group-sequential designs. The first
      method updates the urn at each interim analysis and the second method continually
      updates the urn after each patient response, assuming immediate patient
      responses. Our simulation results show that the group-sequential design, which
      uses the drop-the-loser rule, applied fully sequentially, is the most effective
      method for reducing the expected number of treatment failures and the average
      sample number, whilst still maintaining the nominal error rates, over a range of
      success probabilities.

PMID- 16981178
TI  - IL-15 protects intestinal epithelial cells.
AB  - IL-15, a T-cell growth factor, has been shown to be increased in inflammatory
      bowel disease (IBD). It has been suggested that neutralization of IL-15 could
      protect from T cell-dependent autoimmune inflammation. On the other hand, an anti
      apoptotic effect of IL-15 has been demonstrated in kidney epithelial cells during
      nephritis. We therefore tested the role of IL-15 in two different experimental
      models of colitis in vivo, and in models of intestinal epithelial cell (IEC)
      apoptosis in vitro. IL-15 blockade in chronic dextran sulphate sodium-induced
      colitis resulted in aggravation of the disease with a significantly 2.1-fold
      increased epithelial damage score compared to controls. TUNEL staining clearly
      revealed increased apoptosis. IL-6, TNF and IFN-gamma secretion by mesenteric
      lymph node cells were increased. In the T cell-dependent SCID transfer model of
      colitis IL-15 neutralization reduced the inflammatory infiltration and
      proinflammatory cytokine production. Despite that, the intestinal epithelial
      damage was not reduced. In vitro, IL-15 pre-incubation prevented up to 75% of
      CH11 antibody-induced apoptosis in SW-480 cells and reduced caspase-3 activity.
      According to this, endogenously produced IL-15 in chronic colitis does not only
      act as a proinflammatory cytokine but has at the same time the potential to
      reduce mucosal damage by preventing IEC apoptosis.

PMID- 16981179
TI  - Structural requirements for initiation of cross-reactivity and CNS autoimmunity
      with a PLP139-151 mimic peptide derived from murine hepatitis virus.
AB  - MS is an autoimmune CNS demyelinating disease in which infection appears to be an
      important pathogenic factor. Molecular mimicry, the cross-activation of
      autoreactive T cells by mimic peptides from infectious agents, is a possible
      explanation for infection-induced autoimmunity. Infection of mice with a non
      pathogenic strain of Theiler's murine encephalomyelitis virus (TMEV) engineered
      to express an epitope from Haemophilus influenzae (HI) sharing 6/13 amino acids
      with the dominant proteolipid protein (PLP) epitope, PLP139-151, can induce CNS
      autoimmune disease. Here we demonstrate that another PLP139-151 mimic sequence
      derived from murine hepatitis virus (MHV) which shares only 3/13 amino acids with
      PLP139-151 can also induce CNS autoimmune disease, but only when delivered by
      genetically engineered TMEV, not by immunization with the MHV peptide. Further,
      we demonstrate the importance of proline at the secondary MHC class II contact
      residue for effective cross-reactivity, as addition of this amino acid to the
      native MHV sequence increases its ability to cross-activate PLP139-151-specific
      autoreactive T cells, while substitution of proline in the HI mimic peptide has
      the opposite effect. This study describes a structural requirement for potential
      PLP139-151 mimic peptides, and provides further evidence for infection-induced
      molecular mimicry in the pathogenesis of autoimmune disease.

PMID- 16981180
TI  - Inhibition of CD1d1-mediated antigen presentation by the vaccinia virus B1R and
      H5R molecules.
AB  - Vaccinia virus (VV) has been most commonly used as the vaccine to protect
      individuals against the causative agent of smallpox (variola virus), but it also
      uses a number of strategies meant to evade or blunt the host's antiviral immune
      response. Natural killer T (NKT) cells are a subset of immunoregulatory CD1d
      restricted T lymphocytes believed to bridge the innate and adaptive immune
      responses. It is shown here that the VV-encoded molecules, B1R and H5R, play a
      role in the ability of VV to inhibit CD1d-mediated antigen presentation to NKT
      cells. These are the first poxvirus-encoded molecules identified that can play
      such a role in the evasion of an important component of the innate immune
      response.

PMID- 16981181
TI  - Non-parametric estimation of the case fatality ratio with competing risks data:
      an application to Severe Acute Respiratory Syndrome (SARS).
AB  - For diseases with some level of associated mortality, the case fatality ratio
      measures the proportion of diseased individuals who die from the disease. In
      principle, it is straightforward to estimate this quantity from individual follow
      up data that provides times from onset to death or recovery. In particular, in a
      competing risks context, the case fatality ratio is defined by the limiting value
      of the sub-distribution function, F(1)(t) = Pr(T <or=t and J = 1), associated
      with death, as t --> infinity, where T denotes the time from onset to death (J =
      1) or recovery (J = 2). When censoring is present, however, estimation of
      F(1)(infinity) is complicated by the possibility of little information regarding
      the right tail of F(1), requiring use of estimators of F(1)(t(*)) or
      F(1)(t(*))/(F(1)(t(*))+F(2)(t(*))) where t(*) is large, with F(2)(t) = Pr(T <or=t
      and J = 2) being the analogous sub-distribution function associated with
      recovery. With right censored data, the variability of such estimators increases
      as t(*) increases, suggesting the possibility of using estimators at lower values
      of t(*) where bias may be increased but overall mean squared error be smaller.
      These issues are investigated here for non-parametric estimators of F(1) and
      F(2). The ideas are illustrated on case fatality data for individuals infected
      with Severe Acute Respiratory Syndrome (SARS) in Hong Kong in 2003.

PMID- 16981182
TI  - Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell
      responses during Friend retrovirus infection.
AB  - Cytolytic CD8+ T cells are critical for the control of acute Friend virus (FV)
      infection yet they fail to completely eliminate the virus during chronic
      infection because they are functionally impaired by regulatory T cells (Treg). We
      performed a kinetic analysis of T cell responses during FV infection to determine
      when dysfunction of CD8+ T cells and suppressive activity of CD4+ regulatory T
      cells develops. At 1 week post infection, virus-specific CD8+ T cells with
      effector phenotype and cytolytic potential expanded. Peak expansion was found at
      12 days post infection, correlating with peak viral loads. After 2 weeks when
      viral loads dropped, numbers of activated CD8+ T cells started to decline.
      However, a population of virus-specific CD8+ T cells with effector phenotype was
      still detectable subsequently, but these cells had lost their ability to produce
      granzymes and to degranulate cytotoxic molecules. Contemporaneous with the
      development of CD8+ T cell dysfunction, different CD4+ T cell populations
      expressing cell surface markers for Treg and the Treg-associated transcription
      factor Foxp3 expanded. Transfer as well as depletion experiments indicated that
      regulatory CD4+ cells developed during the second week of FV infection and
      subsequently suppressed CD8+ T cell functions, which was associated with impaired
      virus clearance.

PMID- 16981183
TI  - gammadelta T cells condition dendritic cells in vivo for priming pulmonary CD8 T
      cell responses against Mycobacterium tuberculosis.
AB  - gammadelta T cells and dendritic cells are quickly recruited to the lungs shortly
      after intranasal vaccination with BCG, but the functional in vivo interplay
      between these two cell populations and its role in the induction of adaptive
      immune responses is unclear. Using TCR-deficient mice and bone marrow chimeras,
      we show here that gammadelta T cells provide a non-redundant early source of IFN
      gamma in vivo, which enhances IL-12 production by lung dendritic cells. The in
      vivo-conditioned dendritic cells, in turn, prime a more efficient lung CD8 T cell
      response against Mycobacterium tuberculosis. Thus, strategies exploiting
      gammadelta T cell function and IFN-gamma production could be valuable for the
      design and testing of mucosal vaccines.

PMID- 16981184
TI  - Evidence-based sample size calculations based upon updated meta-analysis.
AB  - Meta-analyses of randomized controlled trials (RCTs) provide the highest level of
      evidence regarding the effectiveness of interventions and as such underpin much
      of evidence-based medicine. Despite this, meta-analyses are usually produced as
      observational by-products of the existing literature, with no formal
      consideration of future meta-analyses when individual trials are being designed.
      Basing the sample size of a new trial on the results of an updated meta-analysis
      which will include it, may sometimes make more sense than powering the trial in
      isolation. A framework for sample size calculation for a future RCT based on the
      results of a meta-analysis of the existing evidence is presented. Both fixed and
      random effect approaches are explored through an example. Bayesian Markov Chain
      Monte Carlo simulation modelling is used for the random effects model since it
      has computational advantages over the classical approach. Several criteria on
      which to base inference and hence power are considered. The prior expectation of
      the power is averaged over the prior distribution for the unknown true treatment
      effect. An extension to the framework allowing for consideration of the design
      for a series of new trials is also presented. Results suggest that power can be
      highly dependent on the statistical model used to meta-analyse the data and even
      very large studies may have little impact on a meta-analysis when there is
      considerable between study heterogeneity. This raises issues regarding the
      appropriateness of the use of random effect models when designing and drawing
      inferences across a series of studies.

PMID- 16981185
TI  - An efficient test for the analysis of dichotomized variables when the reliability
      is known.
AB  - A difference in an outcome variable between the treatment groups in a trial does
      not necessarily mean that there is a difference in the number of patients who
      experience relevant improvement on that variable. When the relevant improvement
      corresponds with an outcome or change in outcome that exceeds a certain
      threshold, the outcome variable can be dichotomized. A responder is a patient
      whose outcome exceeds the threshold. Comparisons can be made between the number
      of responders in the two treatment groups using logistic regression, or some
      other method to evaluate binary outcomes. An important disadvantage of this
      approach is the loss of power. In general, it is more efficient to test the
      difference between the mean values. We developed a statistical test that compares
      response rates for a dichotomized variable. It requires that an estimate of the
      reliability of the outcome variable is available. Simulations showed that the
      test was valid and robust over a wide range of distributions and sample sizes.
      The power was greater than the power of a chi(2) test, which would enable
      substantial reduction in the sample size.

PMID- 16981186
TI  - Fibrin gel improved the spatial uniformity and phenotype of human chondrocytes
      seeded on collagen scaffolds.
AB  - A scaffold made of equine collagen type I based material has been assessed for
      its use in the preparation of tissue-engineered cartilage implants with human
      articular chondrocytes. Improvements of cell-seeding efficiency and specific gene
      expression were studied by combining solid scaffold with fibrin glue or human
      blood plasma. Following 3 weeks of static culture, mRNA expression levels of
      collagen type I, collagen type II, aggrecan and versican were analyzed by real
      time quantitative PCR and compared to those in native cartilage and monolayer
      cell cultures. Constructs prepared with fibrin glue or plasma showed higher cell
      seeding efficiencies than those prepared without gel. Chondrocytes seeded
      directly onto a collagen scaffold appeared fibroblastic in shape while those
      encapsulated in fibrin gel were spherical. The presence of fibrin glue positively
      influences on mRNA levels of collagen type II and aggrecan, while blood plasma
      enhanced only the level of collagen type II expression. Levels of collagen type I
      and versican decreased in presence of fibrin glue. In orthopaedics, the
      combination of solid collagen fleece with fibrin gel for implant preparation is
      seen to be preferred over solid material or even cells in a suspension, since
      fibrin gel improves seeding capacity of the scaffold, supports equal distribution
      of cells and stimulates higher chondrogenic phenotype expression.

PMID- 16981187
TI  - Legacy of the Pacific Islander cancer control network.
AB  - The groundwork for the Pacific Islander cancer control network (PICCN) began in
      the early 1990s with a study of the cancer control needs of American Samoans. The
      necessity for similar studies among other Pacific Islander populations led to the
      development of PICCN. The project's principal objectives were to increase cancer
      awareness and to enhance cancer control research among American Samoans, Tongans,
      and Chamorros. PICCN was organized around a steering committee and 6 community
      advisory boards, 2 from each of the targeted populations. Membership included
      community leaders, cancer control experts, and various academic and technical
      organizations involved with cancer control. Through this infrastructure, the
      investigators developed new culturally sensitive cancer education materials and
      distributed them in a culturally appropriate manner. They also initiated a cancer
      control research training program, educated Pacific Islander students in this
      field, and conducted pilot research projects. PICCN conducted nearly 200 cancer
      awareness activities in its 6 study sites and developed cancer educational
      materials on prostate, colorectal, lung, breast, and cervical cancer and tobacco
      control in the Samoan, Tongan, and Chamorro languages. PICCN trained 9 students
      who conducted 7 pilot research projects designed to answer important questions
      regarding the cancer control needs of Pacific Islanders and to inform
      interventions targeting those needs. The legacy of PICCN lies in its advancement
      of improving cancer control among Pacific Islanders and setting the stage for
      interventions that will help to eliminate cancer-related health disparities.
      Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16981188
TI  - Enhancing the private provision of care through premiums for ability: the case of
      tuberculosis care in the Philippines.
AB  - This paper examines how premiums for ability are set and how these can enhance
      the quality of care provided in private markets. The specific context for this
      study is the market for tuberculosis (TB) care in the Philippines. While the most
      cost- and clinically-effective treatment method known as TB Directly Observed
      Treatment Short Course (TB DOTS) is increasingly being provided by the public
      sector, few private doctors have adopted this protocol. As findings of
      multivariate regression analyses of private physicians' fees suggest, this low
      adoption rate can be partly explained by the modest premiums private doctors
      receive for using TB DOTS. While the public provision of TB DOTS should be
      pursued in earnest, this paper argues that the complementarity between public and
      private provision of TB DOTS should be strengthened, especially since Filipino TB
      patients seem to prefer private doctors. This goal can be achieved through user
      fees that (i) include a sufficiently large premium for physician ability and (ii)
      are paid through the social insurance system.

PMID- 16981189
TI  - APC gene methylation is inversely correlated with features of the CpG island
      methylator phenotype in colorectal cancer.
AB  - The notion of a CpG island methylator phenotype (CIMP) was proposed to describe a
      subset of colorectal cancers (CRC) displaying frequent and concordant methylation
      of CpG islands located within gene promoter regions. Some workers have failed to
      observe associations between CIMP and specific clinicopathological features of
      CRC, possibly because of the choice of genes used to define this phenotype. The
      aim of the current study was to determine whether the aberrant methylation of 6
      genes implicated in CRC development was associated with the same phenotypic
      features of this tumour type. The MethyLight assay was used to provide
      quantitative estimates of MLH1, P16, TIMP3, P14, DAPK and APC methylation levels
      in 199 unselected colorectal tumours. The methylation of MLH1, P16, TIMP3 and P14
      was highly concordant (p < 0.0001 for each pair) but that of DAPK and APC was
      not. An inverse association was observed between the methylation of APC and TIMP3
      (p = 0.004). Methylation of the MLH1, P16, TIMP3 and P14 genes was associated
      with tumour infiltrating lymphocytes (p < 0.05), microsatellite instability (p <
      0.001), BRAF mutation (p < 0.0001) and elevated concentrations of the methyl
      group carriers tetrahydrofolate (THF) and 5,10-methylene THF (p < 0.05). In
      contrast, APC methylation was associated with wildtype BRAF (p = 0.003) and with
      lower concentrations of methyl group carriers (p < 0.05). These findings
      highlight the importance of gene selection in studies that aim to characterize
      the biological features and clinical behaviour of CIMP+ tumours.

PMID- 16981190
TI  - Elasticities of market shares and social health insurance choice in Germany: a
      dynamic panel data approach.
AB  - In 1996, free choice of health insurers was introduced to the German social
      health insurance system. One objective was to increase efficiency through
      competition. A crucial precondition for effective competition among health
      insurers is that consumers search for lower-priced health insurers. We test this
      hypothesis by estimating the price elasticities of insurers' market shares. We
      use unique panel data and specify a dynamic panel model to explain changes in
      market shares. Estimation results suggest that short-run price elasticities are
      smaller than previously found by other studies. In the long-run, however,
      estimation results suggest substantial price effects.

PMID- 16981191
TI  - Are low ultraviolet B and high animal protein intake associated with risk of
      renal cancer?
AB  - Incidence rates of kidney cancer are thought to be highest in places situated at
      high latitudes and in populations with high intake of energy from animal sources.
      This suggests that low 25-hydroxyvitamin D status, due to lower levels of UVB
      irradiance, and energy from animal sources might be involved in etiology. The
      association of latitude with age-adjusted incidence rates was determined for all
      175 countries in a UN cancer database, GLOBOCAN. The independent association of
      UVB irradiance, cloud cover and intake of calories from animal sources with age
      adjusted incidence rates was assessed using multiple regression in 139 countries
      that provided dietary data. Renal cancer incidence rates were highest in
      countries situated at the highest latitudes, in men (R(2) = 0.64, p < 0.01) and
      women (R(2) = 0.63, p < 0.01). According to multivariate analysis in men, UVB
      irradiance was inversely associated with renal cancer incidence rates (p =
      0.0003), while cloud cover (p = 0.003) and intake of calories from animal sources
      (p < 0.0001) were independently positively associated (R(2) for model = 0.73, p <
      0.0001). In women, UVB irradiance was inversely associated with incidence rates
      (p = 0.04), while total cloud cover (p = 0.0008) and calories from animal sources
      (p < 0.0001) were positively associated (R(2) = 0.68, p < 0.0001). Lower levels
      of UVB irradiance and higher intakes of calories from animal sources were
      independently associated with higher incidence rates of kidney cancer.

PMID- 16981192
TI  - Predicting costs over time using Bayesian Markov chain Monte Carlo methods: an
      application to early inflammatory polyarthritis.
AB  - This article focuses on the modelling and prediction of costs due to disease
      accrued over time, to inform the planning of future services and budgets. It is
      well documented that the modelling of cost data is often problematic due to the
      distribution of such data; for example, strongly right skewed with a significant
      percentage of zero-cost observations. An additional problem associated with
      modelling costs over time is that cost observations measured on the same
      individual at different time points will usually be correlated. In this study we
      compare the performance of four different multilevel/hierarchical models (which
      allow for both the within-subject and between-subject variability) for analysing
      healthcare costs in a cohort of individuals with early inflammatory polyarthritis
      (IP) who were followed-up annually over a 5-year time period from 1990/1991. The
      hierarchical models fitted included linear regression models and two-part models
      with log-transformed costs, and two-part model with gamma regression and a log
      link. The cohort was split into a learning sample, to fit the different models,
      and a test sample to assess the predictive ability of these models. To obtain
      predicted costs on the original cost scale (rather than the log-cost scale) two
      different retransformation factors were applied. All analyses were carried out
      using Bayesian Markov chain Monte Carlo (MCMC) simulation methods.

PMID- 16981193
TI  - Expected value of information and decision making in HTA.
AB  - Decision makers within a jurisdiction facing evidence of positive but uncertain
      incremental net benefit of a new health care intervention have viable options
      where no further evidence is anticipated to:(1)adopt the new intervention without
      further evidence;(2)adopt the new intervention and undertake a trial; or(3)delay
      the decision and undertake a trial.Value of information methods have been shown
      previously to allow optimal design of clinical trials in comparing option (2)
      against option (1), by trading off the expected value and cost of sample
      information. However, this previous research has not considered the effect of
      cost of reversal on expected value of information in comparing these options.
      This paper demonstrates that, where a new intervention is adopted, the expected
      value of information is reduced under optimal decision making with costs of
      reversing decisions. Further, the paper shows that comparing expected net gain of
      optimally designed trials for option (2) vs (1) conditional on cost of reversal,
      and (3) vs (1) conditional on opportunity cost of delay allow systematic
      identification of an optimal decision strategy and trial design.

PMID- 16981194
TI  - Public health expenditure and spatial interactions in a decentralized national
      health system.
AB  - One of the limitations of cross-country health expenditure analysis refers to the
      fact that the financing, the internal organization and political restraints of
      health care decision-making are country-specific and heterogeneous. Yet, a way
      through is to examine the influence of such effects in those countries that have
      undertaken decentralization processes. In such a setting, it is possible to
      examine potential expenditure spillovers across the geography of a country as
      well as the influence of the political ideology of regional incumbents and
      institutional factors on public health expenditure. This paper examines the
      determinants of public health expenditure within Spanish region-states
      (Autonomous Communities, ACs), most of them subject to similar financing
      structures although exhibiting significant heterogeneity as a result of the
      increasing decentralization, region-specific political factors along with
      different use of health care inputs, economic dimension and spatial interactions.

PMID- 16981195
TI  - Effects of different immersion media in multiphoton imaging of the epithelium and
      dermis of human skin.
AB  - In this work, we compared the performance of objectives with similar numerical
      aperture of 0.75 but different immersion media of air, water, glycerin, and oil
      in the imaging of human skin epithelium and dermis. In general, we found that the
      oil immersion objective recorded the strongest intensity at the same mechanical
      depth. We also characterized the focal shifts and found that with decreasing
      refractive index, the focal shift becomes increasingly more negative (for both
      the epithelium and dermis). In imaging the dermis, we estimated the image
      resolution at the depths of 18.8 and 30.2 microm, and found that the image
      resolution were comparable at these depths under the four types of immersion
      conditions. Our results demonstrate that by changing the immersion media, the
      main microscopic imaging effects are the recorded axial intensities and the focal
      shifts. The effects on the image resolution are negligible.

PMID- 16981196
TI  - Manipulation, dissection, and lithography using modified tapping mode atomic
      force microscope.
AB  - A modified tapping mode of the atomic force microscope (AFM) was introduced for
      manipulation, dissection, and lithography. By sufficiently decreasing the
      amplitude of AFM tip in the normal tapping mode and adjusting the setpoint, the
      tip-sample interaction can be efficiently controlled. This modified tapping mode
      has some characteristics of the AFM contact mode and can be used to manipulate
      nanoparticles, dissect biomolecules, and make lithographs on various surfaces.
      This method did not need any additional equipment and it can be applied to any
      AFM system.

PMID- 16981197
TI  - Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells
      with angiogenic potential and enhanced multidrug resistance phenotype.
AB  - We investigated in vitro the properties of selected populations of cancer stem
      like cells defined as tumorospheres that were obtained from human glioblastoma.
      We also assessed their potential and capability of differentiating into mature
      cells of the central nervous system. In vivo, their tumorigenicity was confirmed
      after transplantation into the brain of non-obese diabetic/severe combined
      immunodeficient (NOD-SCID) mice. The angiogenic potential of tumorospheres and
      glioblastoma-derived cells grown as adherent cells was revealed by evaluating the
      release of angiogenic factors such as vascular endothelial growth factor and
      CXCL12 by ELISA, as well as by rat aortic ring assay. The proliferative response
      of tumorospheres in the presence of CXCL12 was observed for the first time.
      Multidrug resistance-associated proteins 1 and 3 as well as other molecules
      conferring multidrug resistance were higher when compared with primary adherent
      cells derived from the same tumor. Finally, we obtained cells from the tumor
      developing after grafting that clearly expressed the putative neural stem cell
      marker CD133 as shown by FACS analysis and also nestin and CXCR4. The cells'
      positivity for glial fibrillary acidic protein was very low. Moreover these cells
      preserved their angiogenic potential. We conclude that human glioblastoma could
      contain tumor cell subsets with angiogenic and chemoresistance properties and
      that this chemoresistance potential is highly preserved by immature cells whereas
      the angiogenic potential is, to a higher extent, a property of mature cells. A
      better understanding of the features of these cell subsets may favor the
      development of more specifically targeted therapies.

PMID- 16981198
TI  - Survival of DA neurons is independent of CREM upregulation in absence of CREB.
AB  - cAMP response element binding protein (CREB) and the related factors CREM (cAMP
      response element modulator) and ATF1 (activation transcription factor 1) are bZIP
      domain-containing transcription factors activated through cAMP and other
      signaling pathways. The disruption of CREB function in developing and mature
      neurons affects their development and survival when associated with loss of CREM.
      Since dopaminergic (DA) neurons are affected in several neurological diseases, we
      generated CREB conditional mutants in DA neurons by using a newly generated
      transgenic Cre line targeting the dopaminergic system (DATCre). Here we report
      the generation and analysis of mutant mice lacking CREB in DA neurons
      (CREB(DATCre) mutants). During adulthood, lack of CREB leads to a partial loss of
      DA neurons. Since CREM is upregulated in absence of CREB, we have introduced this
      mutation in a CREM-/- genetic background to assess a compensatory role of CREM.
      Additional inactivation of CREM does not lead to a more severe phenotype.

PMID- 16981199
TI  - Site-specific recombination systems for the genetic manipulation of eukaryotic
      genomes.
AB  - Site-specific recombination systems, such as the bacteriophage Cre-lox and yeast
      FLP-FRT systems, have become valuable tools for the rearrangement of DNA in
      higher eukaryotes. As a first step to expanding the repertoire of recombination
      tools, we screened recombination systems derived from the resolvase/invertase
      family for site-specific recombinase activity in the fission yeast
      Schizosaccharomyces pombe. Here, we report that seven recombination systems, four
      from the small serine resolvase subfamily (CinH, ParA, Tn1721, and Tn5053) and
      three from the large serine resolvase subfamily (Bxb1, TP901-1, and U153), can
      catalyze site-specific deletion in S. pombe. Those from the large serine
      resolvase subfamily were also capable of site-specific integration and inversion.
      In all cases, the recombination events were precise. Functional operation of
      these recombination systems in the fission yeast holds promise that they may be
      further developed as recombination tools for the site-specific rearrangement of
      plant and animal genomes.

PMID- 16981200
TI  - Comparison of multiple Amber force fields and development of improved protein
      backbone parameters.
AB  - The ff94 force field that is commonly associated with the Amber simulation
      package is one of the most widely used parameter sets for biomolecular
      simulation. After a decade of extensive use and testing, limitations in this
      force field, such as over-stabilization of alpha-helices, were reported by us and
      other researchers. This led to a number of attempts to improve these parameters,
      resulting in a variety of "Amber" force fields and significant difficulty in
      determining which should be used for a particular application. We show that
      several of these continue to suffer from inadequate balance between different
      secondary structure elements. In addition, the approach used in most of these
      studies neglected to account for the existence in Amber of two sets of backbone
      phi/psi dihedral terms. This led to parameter sets that provide unreasonable
      conformational preferences for glycine. We report here an effort to improve the
      phi/psi dihedral terms in the ff99 energy function. Dihedral term parameters are
      based on fitting the energies of multiple conformations of glycine and alanine
      tetrapeptides from high level ab initio quantum mechanical calculations. The new
      parameters for backbone dihedrals replace those in the existing ff99 force field.
      This parameter set, which we denote ff99SB, achieves a better balance of
      secondary structure elements as judged by improved distribution of backbone
      dihedrals for glycine and alanine with respect to PDB survey data. It also
      accomplishes improved agreement with published experimental data for
      conformational preferences of short alanine peptides and better accord with
      experimental NMR relaxation data of test protein systems.

PMID- 16981201
TI  - Molecular dynamics simulations of Hydrogenobacter thermophilus cytochrome c552:
      comparisons of the wild-type protein, a b-type variant, and the apo state.
AB  - Molecular dynamic simulations have been performed for wild-type Hydrogenobacter
      thermophilus cytochrome c(552), a b-type variant of the protein, and the apo
      state with the heme prosthetic group removed. In the b-type variant, Cys 10 and
      Cys 13 were mutated to alanine residues, and so the heme group was no longer
      covalently bound to the protein. Two 8-ns simulations have been performed for
      each system at 298 and 360 K. The simulations of the wild-type protein at 298 K
      show a very close agreement with experimental NMR data. A fluxional process
      involving the side chain of Met 59, which coordinates to the heme iron, is
      observed in accord with proposals from NMR studies. Overall, the structure and
      dynamical behavior of the protein during the simulations of the b-type variant is
      closely similar to that of the wild-type protein. However, side chains in the
      heme-binding site show larger fluctuations in the b-type variant simulation at
      360 K. In addition, structural changes are seen for a number of residues close to
      the heme group, particularly Gly 22 and Ser 51. The simulations of the apo state
      show significant conformational changes for residues 50-59. These residues form a
      loop region, which packs over the heme group in the wild-type protein and
      hydrogen bonds to the heme propionate groups. In the absence of heme, in the apo
      state simulations, these residues form short but persistent regions of beta-sheet
      secondary structure. These could provide nucleation sites for the conversion to
      amyloid fibrils.

PMID- 16981202
TI  - A novel high resolution Calpha--Calpha distance dependent force field based on a
      high quality decoy set.
AB  - This work presents a novel C(alpha)--C(alpha) distance dependent force field
      which is successful in selecting native structures from an ensemble of high
      resolution near-native conformers. An enhanced and diverse protein set, along
      with an improved decoy generation technique, contributes to the effectiveness of
      this potential. High quality decoys were generated for 1489 nonhomologous
      proteins and used to train an optimization based linear programming formulation.
      The goal in developing a set of high resolution decoys was to develop a simple,
      distance-dependent force field that yields the native structure as the lowest
      energy structure and assigns higher energies to decoy structures that are quite
      similar as well as those that are less similar. The model also includes a set of
      physical constraints that were based on experimentally observed physical behavior
      of the amino acids. The force field was tested on two sets of test decoys not in
      the training set and was found to excel on all the metrics that are widely used
      to measure the effectiveness of a force field. The high resolution force field
      was successful in correctly identifying 113 native structures out of 150 test
      cases and the average rank obtained for this test was 1.87. All the high
      resolution structures (training and testing) used for this work are available
      online and can be downloaded from http://titan.princeton.edu/HRDecoys.

PMID- 16981203
TI  - Structural basis for the observed differential magnetic anisotropic tensorial
      values in calcium binding proteins.
AB  - Lanthanide ions (Ln(3+)), which have ionic radii similar to those of Ca(2+), can
      displace the latter in a calcium binding protein, without affecting its tertiary
      structure. The paramagnetic Ln(3+) possesses large anisotropic magnetic
      susceptibilities and produce pseudocontact shifts (PCSs), which have r(-3)
      dependence. The PCS can be seen for spins as far as 45 A from the paramagnetic
      ion. They aid in structure refinement of proteins by providing long-range
      distance constraints. Besides, they can be used to determine the interdomain
      orientation in multidomain proteins. This is particularly important in the
      context of a calcium binding protein from Entamoeba histolytica (EhCaBP), which
      consists of two globular domains connected by a flexible linker region containing
      8 residues. As a first step to obtain the interdomain orientation in EhCaBP, a
      suite of 2D and 3D heteronuclear experiments were recorded on EhCaBP by
      displacing calcium with Ce(3+), Ho(3+), Er(3+), Tm(3+), Dy(3+), and Yb(3+) ions
      in separate experiments, and the PCS of (1)H(N) and (15)N spins were measured.
      Such data have been used in the refinement of the individual domain structures of
      the protein in parallel with the calculation of the respective magnetic
      anisotropy tensorial values, which differ substantially (2.1-2.8 times) from what
      is found in other Ca(2+) binding loops. This study provides a structural basis
      for such variations in the magnetic anisotropy tensorial values.

PMID- 16981204
TI  - Aggregation of small peptides studied by molecular dynamics simulations.
AB  - Peptides and proteins tend to aggregate under appropriate conditions. The amyloid
      fibrils that are ubiquitously found among these structures are associated with
      major human diseases like Alzheimer's disease, type II diabetes, and various
      prion diseases. Lately, it has been observed that even very short peptides like
      tetra and pentapeptides can form ordered amyloid structures. Here, we present
      aggregation studies of three such small polypeptide systems, namely, the two
      amyloidogenic peptides DFNKF and FF, and a control (nonamyloidogenic) one, the
      AGAIL. The respective aggregation process is studied by all-atom Molecular
      Dynamics simulations, which allow to shed light on the fine details of the
      association and aggregation process. Our analysis suggests that naturally
      aggregating systems exhibit significantly diverse overall cluster shape
      properties and specific intermolecular interactions. Additional analysis was also
      performed on the previously studied NFGAIL system.

PMID- 16981205
TI  - Prediction of EF-hand calcium-binding proteins and analysis of bacterial EF-hand
      proteins.
AB  - The EF-hand protein with a helix-loop-helix Ca(2+) binding motif constitutes one
      of the largest protein families and is involved in numerous biological processes.
      To facilitate the understanding of the role of Ca(2+) in biological systems using
      genomic information, we report, herein, our improvement on the pattern search
      method for the identification of EF-hand and EF-like Ca(2+)-binding proteins. The
      canonical EF-hand patterns are modified to cater to different flanking structural
      elements. In addition, on the basis of the conserved sequence of both the N- and
      C-terminal EF-hands within S100 and S100-like proteins, a new signature profile
      has been established to allow for the identification of pseudo EF-hand and S100
      proteins from genomic information. The new patterns have a positive predictive
      value of 99% and a sensitivity of 96% for pseudo EF-hands. Furthermore, using the
      developed patterns, we have identified zero pseudo EF-hand motif and 467
      canonical EF-hand Ca(2+) binding motifs with diverse cellular functions in the
      bacteria genome. The prediction results imply that pseudo EF-hand motifs are
      phylogenetically younger than canonical EF-hand motifs. Our prediction of Ca(2+)
      binding motifs provides not only an insight into the role of Ca(2+) and Ca(2+)
      binding proteins in bacterial systems, but also a way to explore and define the
      role of Ca(2+) in other biological systems (calciomics).

PMID- 16981206
TI  - Stereochemistry of guanidine-metal interactions: implications for L-arginine
      metal interactions in protein structure and function.
AB  - The geometries of 150 guanidine-metal ion interactions retrieved from crystal
      structures deposited in the Cambridge Structural Database have been analyzed.
      Metal ions exhibit a preference for anti coordination stereochemistry in the
      plane of the unprotonated guanidine group, usually in chelate complexes with a
      diguanidine moiety, but syn-oriented interactions are occasionally found for
      single guanidine-metal interactions. Three L-arginine-metal coordination
      interactions are found in metalloenzyme structures deposited in the Protein Data
      Bank: biotin synthase from E. coli, His-67 --> Arg human carbonic anhydrase I,
      and inactivated B. caldovelox arginase complexed with L-arginine. In these
      proteins, L-arginine-metal coordination adopts syn/out-of-plane and anti/in-plane
      coordination stereochemistry. The implications of these results for L-arginine
      metal interactions in protein structure and function are discussed. Although such
      interactions are rare, this analysis serves as a useful reference point for the
      growing interest in enzymes containing L-arginine residues that function as
      general bases or metal ligands.

PMID- 16981207
TI  - Reversal of regioselectivity and enhancement of rates of nitrile oxide
      cycloadditions through transient attachment of dipolarophiles to cyclodextrins.
AB  - The reactions of nitrile oxides with monosubstituted dipolarophiles, such as
      propiolamide, typically afford proportionally 80 % or more of the 3,5
      disubstituted cycloadducts. By contrast, the reactions of 6(A)-deoxy-6(A)
      propynamido-beta-cyclodextrin with 4-tert-butylbenzonitrile oxide and 4
      phenylbenzonitrile oxide afford >90 % and approximately 85 % of the corresponding
      3,4-disubstituted isoxazoles, respectively. As well as reversing the
      regioselectivity, the cyclodextrin increases the rates of these cycloadditions.
      The extent of the acceleration is up to more than three orders of magnitude for
      the production of the cycloadduct preferred by the cyclodextrin, but even the
      rate of reaction to give the less favored regioisomer is increased. With 6(A)
      deoxy-6(A)-propynamido-beta-cyclodextrin, the cycloadducts are not easily
      separated from the cyclodextrin, as the amide bond is not readily cleaved. In
      comparison, the regioselectivity of the cycloadditions of 4-tert
      butylbenzonitrile oxide with acrylic acid, methacrylic acid, and crotonic acid is
      also altered by formation of the corresponding cyclodextrin esters, by factors of
      500, >10, and >100, respectively. The rates of cycloaddition are also increased
      by up to 475 times, and in these cases the products of cycloaddition are readily
      released from the cyclodextrin through ester hydrolysis. Incorporating these
      processes into a reaction cycle, acylation of beta-cyclodextrin with p
      nitrophenyl acrylate and subsequent treatment first with 4-tert-butylbenzonitrile
      oxide and then with base, the latter to catalyze ester hydrolysis and regenerate
      the beta-cyclodextrin, affords proportionally fivefold more of the 3,4
      disubstituted isoxazoline than is produced directly from acrylic acid.

PMID- 16981208
TI  - Azumamides A-E: histone deacetylase inhibitory cyclic tetrapeptides from the
      marine sponge Mycale izuensis.

PMID- 16981210
TI  - On the correction of the memory effect in isotopic analysis.

PMID- 16981209
TI  - Effect of caffeic acid phenethyl ester on treatment of experimentally induced
      methicillin-resistant Staphylococcus epidermidis endophthalmitis in a rabbit
      model.
AB  - This study investigated the anti-inflammatory effects of caffeic acid phenethyl
      ester (CAPE), a natural bee-produced compound, and compared it with
      corticosteroids in the treatment of experimentally induced methicillin-resistant
      Staphylococcus epidermidis (MRSE) endophthalmitis in addition to intravitreal
      antibiotics. An experimental endophthalmitis model was produced in 24 New Zealand
      albino rabbits by unilateral intravitreal injection of 0.1 ml of 4.7 x 10(4)
      colony-forming units (CFU) methicillin-resistant S. epidermidis. The animals were
      then divided randomly into three treatment groups and a control group, group 1
      (six rabbits), received only intravitreal vancomycin (1.0 mg/0.1 ml); group 2
      (six rabbits), received both intravitreal vancomycin (1.0 mg/0.1 ml) and
      intravitreal dexamethasone (400 microg/0.1 ml) and group 3 (six rabbits),
      received both intravitreal vancomycin (1.0 mg/0.1 ml) and subtenon CAPE (10
      mg/0.3 ml) after 24 h post-infection. No treatment was given to the control
      group. Treatment efficacy was assessed by clinical examination, vitreous culture
      and histopathology. There were no statististically significant differences
      between clinical scores of all groups in examinations at 24 and 48 h post
      infection (p = 0.915 and p = 0.067 respectively), but in examinations at 72 h
      post-infection and after 7 days post-infection, although the clinical scores of
      treatment groups were not significantly different from each other, they were
      significantly lower than the control group (p < 0.05). The culture results of all
      groups were sterile. As a result, CAPE was found to be as effective as
      dexamethasone in reducing inflammation in the treatment of experimental MRSE
      endophthalmitis when used with antibiotics. More studies are needed to determine
      the optimal administration route and effective dosage of this compound.

PMID- 16981211
TI  - On the mechanism of ion formation from the aqueous solutions irradiated with 3
      microm IR laser pulses under atmospheric pressure.
AB  - The mechanism of atmospheric pressure (AP) laser ionization of water and
      water/glycerol liquid samples at a 3-microm wavelength is studied experimentally.
      For the ion desorption, an in-house built Yb : YAG-pumped optical parametric
      oscillator (OPO) infrared (IR) laser has been coupled with AP MALDI ion source
      interfaced to an ion trap mass spectrometer (MS). It has been shown that water is
      primarily responsible for ion generation in water/glycerol samples, while
      glycerol increases the solution viscosity and decreases the water evaporation
      rate and sample losses. In contrast to AP UV-MALDI, the electric field in the
      case of AP IR-MALDI does not assist in ion production. It was found that the
      absence of the electrical field provides the optimum ionization condition both
      for water and water/glycerol liquid samples at the 3-microm laser irradiation. A
      two-stage ion formation mechanism, which includes the initial emission of
      microdroplets and release of molecular ions at the second stage, can explain the
      experimentally observed ion signal dependencies upon the voltage applied between
      MS inlet and the MALDI sample plate. Postionization using additional corona
      discharge APCI increases the observed signal by approximately 50%, which
      indicates that some portion of the analyte is desorbed in the form of neutral
      molecules.

PMID- 16981212
TI  - Quantitative analysis of EO9 (apaziquone) and its metabolite EO5a in human plasma
      by high-performance liquid chromatography under basic conditions coupled to
      electrospray tandem mass spectrometry.
AB  - A sensitive and specific LC-MS/MS assay for the quantitative determination of EO9
      and its metabolite EO5a is presented. A 200-microl human plasma aliquot was
      spiked with a mixture of deuterated internal standards EO9-d3 and EO5a-d4 and
      extracted with 1.25 ml ethyl acetate. Dried extracts were reconstituted in 0.1 M
      ammonium acetate-methanol (7 : 3, v/v) and 25 microl-volumes were injected into
      the HPLC system. Separation was achieved on a 150 x 2.1 mm C18 column using an
      alkaline eluent (1 mM ammonium hydroxide-methanol (gradient system)). Detection
      was performed by positive ion electrospray followed by tandem mass spectrometry.
      The assay quantifies a range from 5 to 2500 ng/ml for EO9 and from 10 to 2500
      ng/ml EO5a using 200 microl of human plasma samples. Validation results
      demonstrate that EO9 and EO5a concentrations can be accurately and precisely
      quantified in human plasma. This assay will be used to support clinical
      pharmacologic studies with EO9.

PMID- 16981213
TI  - Effectiveness and safety of ritodrine hydrochloride for the treatment of preterm
      labour: a systematic review.
AB  - PURPOSE: To analyse the available data on the effectiveness and safety of
      ritodrine hydrochloride in delaying delivery and in decreasing the incidence of
      preterm birth. METHODS: Systematic review of randomised controlled trials (RCTs)
      that compared the effectiveness and safety of ritodrine hydrochloride with a
      placebo or with no treatment. Main outcome measures were relative risks (RRs) for
      perinatal mortality, neonatal respiratory distress syndrome (RDS), delivery
      within 48 hours or 7 days, preterm birth before 37 weeks gestation and low birth
      weight. We searched computerised databases (MEDLINE, CENTRAL, Ichushi Web) from
      their inception to October 2004, and searched the references of eligible trials.
      RESULTS: Seventeen RCTs were included and meta-analysis was conducted. Pooled RRs
      relative to placebo for delivery within 48 hours or 7 days for parenteral
      ritodrine hydrochloride were 0.74 (95%CI (confidential interval): 0.56, 0.97),
      0.85 (95%CI: 0.74, 0.97). There was no significant decrease in perinatal
      mortality, the proportion of RDS, preterm birth and low birth weight infants.
      Maternal side-effects significantly increased in patients receiving ritodrine
      with respect to those receiving a placebo. Pooled RRs relative to placebo for
      oral ritodrine hydrochloride showed no significant decrease in primary and
      secondary endpoints. CONCLUSIONS: The effectiveness of parenteral ritodrine
      hydrochloride for tocolysis in preterm labour is limited to short-range
      prolongation of gestation. The effectiveness of maintenance tocolytic therapy
      with oral ritodrine hydrochloride was not proved.

PMID- 16981214
TI  - Contact allergy to topical drugs: prevalence in a clinical setting and estimation
      of frequency at the population level.
AB  - OBJECTIVES: To estimate the prevalence of contact allergy (CA) to a set of
      topical drugs patch tested in the research network IVDK (Information Network of
      Departments of Dermatology; www.ivdk.org) between 1995 and 2004, and to
      extrapolate these clinical data to the German population. METHODS: Clinical data
      comprised results of allergy patch tests with topical drugs in patients with
      suspected CA. Clinical epidemiology and drug utilization research (CE-DUR)
      methods were employed to grossly estimate the incidence of CA to these topical
      drugs during two 5-year periods (1995-1999 and 2000-2005) in the German general
      population. To estimate the number of persons eligible for patch testing (with
      the topical drugs) on a general population level, sales data of patch test
      material were obtained. By relating this denominator to the CA frequency observed
      in the IVDK, the incidence of CA to selected topical drugs in the German general
      population was crudely estimated. RESULTS: In general, topical aminoglycosides
      showed the highest CA frequencies and, except for gentamicin sulfate, frequencies
      of CA to all other allergens tested were lower in the 2nd period of analysis.
      According to the medium model, 1-year incidence rates ranged from 1
      (hydrocortisone-17-butyrate) to 29 persons/100,000 (neomycin sulfate) in the
      general population (1995-1999). CONCLUSION: The CE-DUR approach yielded incidence
      estimates of CA to relevant topical drugs in the German general population,
      which, despite their limited precision in absolute terms, illustrate the relative
      frequency of this particular adverse effect. However, comparative risk assessment
      should preferably take exposure information into account.

PMID- 16981215
TI  - A call for international harmonization in therapeutic risk management.
AB  - Therapeutic risk management is required to ensure that the benefits of a
      particular drug outweigh the risks in general practice. Current risk management
      strategies and handling of risk management and pharmacovigilance issues differ
      across borders. Differences in key regulatory decisions on the same product
      around the world, including the handling of safety issues with cisapride,
      dofetilide, and isotretinoin, bring into question the robustness of these
      decisions and the procedures currently in place to manage the risks to the public
      of products with potentially unfavorable risk-benefit balances. These differences
      may be partly due to differences in health care systems, regulatory requirements
      and procedures, and cultures. Greater international harmonization in approaches
      to risk management potentially would improve safety of medicines around the world
      by developing a greater uniformity in acquiring and interpreting risk-benefit
      evidence. The appropriateness and effectiveness of risk management interventions
      in different regions should be examined, and international strategies should be
      'fine-tuned' for each regional health care setting. Recently issued international
      guidance on risk management and pharmacovigilance may help to improve consistency
      of decision-making around the world and promote better international
      communication and collaboration.

PMID- 16981216
TI  - Acenocoumarol and vasculitis: a case report.
AB  - A 62-year-old woman was referred to the dermatology department for a history of
      fever, asthenia and cutaneous rash, which appeared after a 3-day course of
      digitalin and acenocoumarol for atrial fibrillation. The physical examination
      revealed multiple round confluent purpuric lesions over her entire legs with no
      blistering. Laboratory exams were all negative. Biopsy of the involved skin was
      compatible with leucocytoclastic vasculitis. The acenocoumarol treatment was
      withheld and the skin lesions resolved spontaneously over the next 10 days. The
      cause of this purpura was seemingly acenocoumarol because of the close temporal
      relationship between exposure to the drug and the onset of the symptoms, and the
      spontaneous resolution of the lesions after acenocoumarol was discontinued. This
      observation illustrates a rare association between vasculitis and acenocoumarol.
      Clinicians should be aware of this potential adverse effect and recommend
      interrupting the drug intake when temporal relation is evocative.

PMID- 16981217
TI  - Protective effect of alpha-tocopherol on oxidative stress in experimental
      pulmonary fibrosis in rats.
AB  - The study was undertaken to investigate the influence of alpha-tocopherol
      (vitamin E) on malondialdehyde (MDA) and glutathione (GSH) levels and catalase
      (CAT) activity in lung of rats with bleomycin-induced pulmonary fibrosis (PF).
      Fourteen Wistar-albino rats were randomly divided into two groups of seven
      animals each. The first group was treated intra-tracheally with bleomycin
      hydrochloride (BM group); the second group was also instilled with BM but
      received injections of alpha-tocopherol twice a week (BM + E group). The third
      group was treated in the same manner with saline solution only, acting as
      controls (C). There were decreases in GSH level and CAT activity while an
      increase in MDA level in BM group was found compared to the control group (p <
      0.05). Vitamin E had a regulator effect on these parameters. After administration
      of alpha-tocopherol, the increase in GSH level and CAT activity and the decrease
      in MDA level were seen in BM + E group compared to BM group (p < 0.05). Distinct
      histopathological changes were found in the BM group compared to the untreated
      rats. Less severe fibrotic lesions were also observed in the BM + E group. The
      results show that vitamin E is effective on the prevention of BM-induced PF, as
      indicated by differences in the lung levels of oxidants and antioxidants.

PMID- 16981218
TI  - Allele frequency distributions of Apo B VNTR locus in Cukurova, Turkey.
AB  - The highly polymorphic minisatellites contain a variable number of tandemly
      repeated (VNTR) DNA sequences. They are extremely useful and informative markers
      to study genetic variation among human populations. We have analysed the allele
      frequency distribution at the highly polymorphic apolipoprotein B (Apo B) VNTR
      locus in order to obtain the population data for the Cukurova region in Turkey by
      using the polymerase chain reaction and polyacrylamide gel electrophoresis. We
      observed 10 different alleles and 21 genotypes in a sample of 100 unrelated
      individuals. The allele frequencies ranged from 0.01 to 0.4, with an expected
      heterozygosity of 0.69 for the Apo B locus. Alleles 37 (frequency = 0.4) and 35
      (frequency = 0.17) were the most common in the Cukurova population. There was a
      significant deviation from the Hardy-Weinberg equilibrium (HWE) for genotype
      frequencies (chi2 = 29.12; df = 1; p = 0.000). This study possesses novelty as it
      is the first DNA polymorphism study conducted at the Cukurova population using an
      Apo B minisatellite locus.

PMID- 16981219
TI  - Fetal aortic root dilation: a prenatal feature of the Loeys-Dietz syndrome.
AB  - Loeys-Dietz syndrome is a recently described autosomal dominant disorder with
      cardinal manifestations in cardiovascular, craniofacial and skeletal systems.
      Although the disease has some phenotypic overlap with Marfan syndrome, the
      disease, that is caused by mutations in the transforming growth factor beta
      receptor 1 (TGFBR1) or transforming growth factor beta-receptor 2 (TGFBR2) genes,
      presents many distinctive features and a particularly aggressive cardiovascular
      course. We describe prenatal identification of an aortic root aneurysm in a fetus
      of 19 week of gestation as an early marker of Loeys-Dietz syndrome.

PMID- 16981220
TI  - An investigation of the long-term benefits of antidepressant medication in the
      recovery of patients with chronic fatigue syndrome.
AB  - Two hundred and seventy-five patients fulfilling the Centre for Disease Control
      (CDC) criteria for Chronic Fatigue Syndrome (CFS) completed measures assessing
      illness history, global ratings of well being, sleep, activity and
      psychopathology at baseline, 6 months, 18 months and 3 year follow-up. Forty-nine
      of these patients had been prescribed antidepressant medication, namely Tricyclic
      drugs or Selective Serotonin Re-uptake Inhibitors (SSRI). Data from the current
      study suggests that patients in the antidepressant medication group recover at a
      faster rate over time when compared to the untreated patient sample. In addition,
      the positive effects of antidepressant therapy are maintained at the 3-year
      follow-up point. It appears from these data that the SSRI in particular are
      responsible for improvements in the condition. Most importantly, these
      improvements include a reduction in the levels of fatigue recorded by patients.
      These findings have not been demonstrated in previous studies of the effect of
      antidepressant therapy for patients with this illness and this may reflect the
      short time periods studied in the earlier research.

PMID- 16981221
TI  - Prenatal diagnosis of neurofibromatosis type 1: sonographic and MRI findings.
AB  - Prenatal ultrasound and magnetic resonance imaging (MRI) demonstrated a large
      oropharyngeal tumor, and cardiac and cranial abnormalities consistent with
      neurofibromatosis type 1 (NF1) in a third-trimester fetus, which were confirmed
      on postmortem examination. Sonographic features of NF1 are generally nonspecific;
      MR examination provided significant additional information, facilitating prenatal
      diagnosis.

PMID- 16981224
TI  - Accurate-mass identification of chlorinated and brominated products of 4
      nonylphenol, nonylphenol dimers, and other endocrine disrupters.
AB  - LC/ToF-MS was used to identify new chlorination and bromination products of 4
      nonylphenol (4-NP), such as 4-NPBr2, 4-NPBrCl, 4-NP dimer (2 isomers), 4-NPCl
      dimer (2 isomers), 4-NPBr dimer, and a series of methoxy bromo and chloro 4-NPs
      from a laboratory study of nonylphenol chlorination. The identification procedure
      used the exact mass, exact mass of the isotope cluster, and their relative
      intensities, at an average mass accuracy of approximately 1 ppm. The products
      were produced by a simulated study of industrial cleaning procedures where 4-NP,
      nonylphenol ethoxylate (NPEO-1 and 2), and nonylphenol carboxylate (NPEC-1) were
      in contact with sodium hypochlorite solutions (with and without bromide) of
      various strengths (possible environmental scenarios) at neutral pH. The formation
      of the products was measured as a function of chlorine concentration, and it was
      found that 4-NP was the most reactive, producing 4-NPCl, 4-NPCl2, 4-NP (dimers),
      and the 4-NPCl (dimers). In the presence of bromide ions, a mixture results with
      products of 4-NPBr2, 4-NPCl, 4-NPCl2, 4-NPBrCl, 4-NPBr, and a 4-NPBr dimer. Less
      reactive to halogenation was NPEO, which formed only the monochloro and monobromo
      products, and the least reactive was NPEC. A simple stereochemical model is used
      to explain halogenation reactivity for the family of 4-NPs and NPEOs at neutral
      pH. The presence of halogenated 4-NP dimers (bromo and chloro diphenyl ethers) is
      discussed as a possible source of new endocrine disrupters.

PMID- 16981222
TI  - Lysophosphatidylcholine promotes cholesterol efflux from mouse macrophage foam
      cells via PPARgamma-LXRalpha-ABCA1-dependent pathway associated with apoE.
AB  - Formation of macrophage-derived foam cells is a hallmark in earlier stages of
      atherosclerosis (AS). Increased cholesterol efflux from macrophage foam cells
      promote atherosclerotic regression. In the present study, lysophosphatidylcholine
      (LPC) promoting cholesterol efflux from macrophage foam cells was observed, and
      the mechanism underlying the action was investigated. Macrophage foam cells from
      mice were incubated with different concentrations of LPC (10, 20, 40, 80 microM),
      and the free cholesterol in medium increased but total intracellular cholesterol
      decreased. At the same time, the expression of PPARgamma, LXRalpha, ABCA1 was
      enhanced in a dose-dependent manner. The treatment of macrophage foam cells with
      40 microM LPC for 12, 24 and 48 h promoted cellular cholesterol efflux in a time
      dependent manner, meanwhile expression of PPARgamma, LXRalpha, ABCA1 was also
      raised respectively. Addition of different specific inhibitors of PPARgamma
      (GW9662), LXRalpha (GGPP), ABCA1 (DIDS) to the foam cells significantly
      suppressed LPC-induced cholesterol efflux. Also treatment with specific
      inhibitors of PPARgamma or LXRalpha decreased ABCA1 mRNA and protein expressions.
      LPC (40 microM)-induced cholesterol efflux was significantly lower in macrophage
      foam cells from apoE deficient mice than from normal C57BL/6J mice. In contrast,
      10 microg apoAI-induced cholesterol efflux from foam cells remained in apoE
      deficient mice. The present results indicate that LPC promotes cholesterol efflux
      from macrophage foam cells via a PPARgamma-LXRalpha-ABCA1-dependent pathway.
      Furthermore, apoE may be involved in this process.

PMID- 16981225
TI  - Covariates missing by design: comparison of the efficient score to other weighted
      methods.
AB  - This paper addresses the modelling of missing covariate data with the logistic
      regression model. The aim of this paper is to evaluate the properties of an
      efficient score for logistic regression in a two-phase design. Simulation studies
      show that the efficient score is more efficient than two other pseudo-likelihood
      methods when the correlation between the missing covariate and its surrogate is
      high or the sampling proportion is small. These methods are illustrated with data
      from the National Wilms Tumor Study Group. Results from the example confirm the
      simulation study findings with the exception that the pseudo-likelihood approach
      produces more reliable estimates than the weighted pseudo-likelihood approach.

PMID- 16981226
TI  - Estimation of optimal dynamic anticoagulation regimes from observational data: a
      regret-based approach.
AB  - A complication of long-term anticoagulation is that the optimal dose level varies
      not only between patients but over time within patients, in response to short
      term changes in lifestyle. Consequently, doseage needs to be adaptive but there
      are as yet no accepted decision rules. Since anticoagulant use is increasing
      worldwide there is a need for more objective and routine procedures. In this
      paper, we describe an analysis of observational longitudinal anticoagulant data,
      aimed at determining an optimal reactive dose-changing strategy. We use the
      regret parameterization approach advocated by Murphy (J. R. Stat. Soc. Ser. B
      2003; 65:331-366). Practical problems encountered in the implementation of the
      approach are discussed and illustrated.

PMID- 16981227
TI  - Effects of DRD2 and CYP2D6 genotypes on delta EEG power response to aripiprazole
      in healthy male volunteers: a preliminary study.
AB  - The aim of the present study was to evaluate the effects of polymorphisms in
      dopamine D2 receptor (DRD2) and cytochrome P450 (CYP) 2D6 genes on delta EEG
      power response to aripiprazole in healthy male volunteers. Seventeen volunteers
      were recruited according to the DRD2 Taq1A genotype, and separated into the
      following groups: homozygous wild-type (A2/A2, n = 7), heterozygous (A2/A1, n =
      5) and homozygous variant-type (A1/A1, n = 5) groups. After enrollment in this
      study, they were genotyped for CYP2D6. The volunteers received single 10 mg oral
      doses of aripiprazole, in accordance with an open-label parallel group study
      design. Plasma levels of aripiprazole and its metabolite were determined and EEGs
      were obtained simultaneously. The pharmacodynamic parameter was absolute delta
      power in the Cz channel. The changes of delta power were not different according
      to DRD2 Taq1A genotypes. As to the CYP2D6 allele, the subjects had the following
      CYP2D6 genotypes: *10/*10 (n = 4), *1/*10 (n = 5), *1/*5 (n = 2), *1/*1 (n = 3),
      *2/*41 (n = 1), *2/*2 (n = 1), *2N/*10 (n = 1). Subjects exhibiting the *1/*5 and
      *1/*10 genotypes showed a trend toward high area under the plasma aripiprazole
      concentration-time curve (AUC), which was linearly related to area under the EEG
      response-time curve (AUEC). Our results demonstrate a need for further evaluation
      of the CYP2D6 genotypic effect on the pharmacodynamics of aripiprazole.

PMID- 16981228
TI  - Migration of immature mouse DC across resting endothelium is mediated by ICAM-2
      but independent of beta2-integrins and murine DC-SIGN homologues.
AB  - Immature dendritic cells (DC) reside in tissues where they initiate immune
      responses by taking up foreign antigens. Since DC have a limited tissue half
      life, the DC pool in tissues has to be replenished constantly. This implies that
      precursor/immature DC must be able to cross non-activated endothelium using as
      yet unknown mechanisms. Here we show that immature, but not mature bone marrow
      derived murine DC migrate across resting endothelial monolayers in vitro. We find
      that endothelial intercellular adhesion molecule-2 (ICAM-2) is a major player in
      transendothelial migration (TEM) of immature DC, accounting for at least 41% of
      TEM. Surprisingly, the ICAM-2-mediated TEM was independent of beta2-integrins,
      the known ICAM-2 ligands, since neither blocking of beta2-integrins with
      antibodies nor the use of CD18-deficient DC affected the ICAM-2-specific TEM. In
      humans, the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) was
      shown to interact with ICAM-2, suggesting a similar role in mice. However, we
      find that none of the murine DC-SIGN homologues mDC-SIGN, murine DC-SIGN-related
      molecule-1 (mSIGN-R1) and mSIGN-R3 is expressed on the surface of bone marrow
      derived mouse DC. Taken together, this study shows that ICAM-2 strongly supports
      transmigration of immature DC across resting endothelium by interacting with
      ligands that are distinct from beta2-integrins and DC-SIGN homologues.

PMID- 16981229
TI  - Studying co-medication patterns: the impact of definitions.
AB  - PURPOSE: To show the necessity of distinguishing several patterns of drug
      prescribing that may lead to co-medication. It is demonstrated how these
      different patterns can be investigated using large databases containing pharmacy
      data or reimbursement data. METHODS: Two examples illustrate how the particular
      pattern of co-medication studied will influence the reported proportion of
      patients having co-medication, the use of antidepressants among people using
      anticonvulsants, and the use of antihistamines among people receiving
      penicillines. RESULTS: Depending on definition and period considered, the
      percentage of anticonvulsant users co-medicated with antidepressants ranged from
      5.8% (95%CI 5.0%, 6.8%) to 14.5% (95%CI 13.2%, 15.9%) in 2000. Comparing 2002
      with 2000, the ratio of proportions ranged from 1.3 to 2.1. The percentage of
      people who received penicillines and were co-medicated with antihistamines ranged
      from 0.5% (95%CI 0.4%, 0.6%) to 9.7% (95%CI 9.3%, 10.2%) in 2000. Comparing 2002
      with 2000, the ratio of proportions ranged from 1.2 to 1.6. CONCLUSION: The co
      medication patterns investigated yielded clinical as well as statistically
      significant different estimates. The estimates differed up to a factor 2.5 for
      the drugs usually prescribed for long periods, and a factor 12 for drugs
      prescribed for short periods. Hence, we propose to distinguish the patterns 'co
      prescribing', 'concomitant medication,' and 'possibly concurrent medication.' The
      research question determines the co-medication pattern of interest, and the drug
      and disease under study determine the time window.

PMID- 16981230
TI  - Risk of local adverse events by gender following cardiac catheterization.
AB  - PURPOSE: To assess the reason for the relative high risk of local complications
      for women following cardiac catheterization by evaluating the associations
      between gender, sheath size, and local adverse outcomes following cardiac
      catheterization. METHODS: The data used in this study were obtained from a
      portion of the American College of Cardiology-National Cardiovascular Data
      Registry (ACC-NCDR), which included 13 878 patients who underwent cardiac
      catheterization at one of 59 participating cardiac catheterization institutions
      throughout the United States during late 2003. Rates of serious local vascular
      adverse events were calculated by gender following cardiac catheterization, by
      type of vascular hemostasis used, stratified by arterial sheath size. RESULTS:
      Serious local vascular events were reported in 3.54% of patients, most commonly
      hematoma (2.00%). The relative risk for women of any vascular complication was
      1.40 [95%CI = 1.17, 1.67, p = 0.0002]. A statistically significant relative risk
      for woman was evident when collagen plug devices or manual compression alone were
      used as the first method for hemostasis. The rate of vascular complications
      increased progressively with increasing sheath size, more so in women than in
      men. CONCLUSIONS: High relative risk for women of local vascular complications
      following cardiac catheterization was demonstrated with use of manual
      compression, as well as with collagen plug devices to control femoral artery
      bleeding. Large sheath size is associated with both a relatively high absolute
      risk and a high relative risk for women. Knowledge of this information should be
      considered by interventional cardiologists in making decisions on how to achieve
      hemostasis following cardiac catheterization.

PMID- 16981231
TI  - Determination of glyoxylyl-peptide concentration using oxime chemistry and RP
      HPLC analysis.
AB  - Glyoxylyl-peptides are useful peptide derivatives in the context of hydrazone,
      oxime or thiazolidine ligations. We describe a method for the determination of
      glyoxylyl-peptide concentration based on the reaction of the alpha-oxo aldehyde
      group with an excess of O-benzylhydroxylamine. The amount of O
      benzylhydroxylamine necessary to convert the alpha-oxo aldehyde group into the
      corresponding O-benzyloxime was determined by RP-HPLC analysis and corresponded
      to the quantity of glyoxylyl-peptide used in the experiment. The method is rapid,
      sensitive, accurate and allows the automated analysis of several samples.

PMID- 16981232
TI  - Differential capacity of anti-RAP and anti-megalin antibodies to produce
      progressive passive Heymann nephritis - implications for the pathogenesis of
      idiopathic human membranous glomerulonephritis.
AB  - Passive Heymann nephritis (PHN) induced with heterologous antisera has been
      described according to various criteria, which may or may not include induction
      of chronic disease and proteinuria. Characteristics of the glomerular immune
      deposits determined by the antigenic specificities of the antisera presumably
      account for differences in disease outcome. In this study, the clinical and
      immunohistological features in the model produced with monospecific antisera were
      compared against megalin or receptor associated protein (RAP), two proteins that
      have been implicated as target antigens in PHN. Rats injected with either anti
      megalin or anti-RAP antiserum developed typical glomerular immune deposits of PHN
      when examined after 7 days. Although the deposits stained for complement, none of
      the animals had abnormal proteinuria in this time frame. Over a longer time
      course (7-16 weeks), immune deposits persisted and proteinuria increased to
      pathological levels in all animals injected with anti-megalin serum. By contrast,
      immune deposits had cleared from the kidneys of rats injected with anti-RAP
      antiserum when examined at 7-8 weeks post-injection and the proteinuria levels
      observed up to 13 weeks remained in the normal range. Additional doses of anti
      RAP antiserum given 4 and 17 days after the first injection did not prolong the
      duration of glomerular immune deposits. These results demonstrate a clear
      divergence in pathogenic potential of antisera generated against the two renal
      antigens, which suggest differences in the immune deposits linked to a soluble
      antigen that is non-covalently bound to the podocyte membrane versus those linked
      to an integral membrane antigen. These observations could provide clues to the
      nature of the unknown glomerular autoantigen of idiopathic membranous
      glomerulonephritis in humans.

PMID- 16981233
TI  - Numerical characterization of DNA sequences based on the k-step Markov chain
      transition probability.
AB  - A DNA sequence can be regarded as a discrete-time Markov chain. Based on k-step
      transition probabilities, we construct a series of 4 x 4 k-step transition
      matrices to characterize the DNA primary sequences. According to the properties
      of Markov chains, we obtain distributions of A, T, C and G, and analyze the
      changes among them from yesterday to tomorrow. We can calculate the probabilities
      of nucleotide triples of DNA primary sequences. Finally, we introduce a
      correlation of this kind of transition matrices and consider it as an invariant
      to analyze the similarities/dissimilarities of DNA sequences.

PMID- 16981234
TI  - Transition metal-boron complexes BnM: from bowls (n = 8-14) to tires (n = 14).
AB  - Transition metal-boron complexes BnM have been predicted at density functional
      theory level to be molecular bowls (n = 8-14) hosting a transition metal atom (M)
      inside or molecular tires (n = 14) centered with a transition metal atom. Small
      Bn clusters prove to be effective inorganic ligands to all the VB-VIIIB
      transition metal elements in the periodic table. Density functional evidences
      obtained in this work strongly suggest that bowl-shaped fullerene analogues of Bn
      units exist in small BnM complexes and the bowl-to-tire structural transition
      occur to the first-row transition metal complexes BnM (M = Mn, Fe, Co) at n = 14,
      a size obviously smaller than n = 20 where the 2D-3D structural transition occurs
      to bare Bn. The half-sandwich-type B12Cr (C3v), full sandwich-type (B12)2Cr
      (D3d), bowl-shaped B14Fe (C2), and tire-shaped B14Fe (D7d) and B14Fe- (C7v) are
      the most interesting prototypes to be targeted in future experiments. These BnM
      complexes may serve as building blocks to form extended boron-rich BnMm tubes or
      cages (m > or = 2) or as structural units to be placed inside carbon nanotubes
      with suitable diameters.

PMID- 16981235
TI  - Ab initio studies on isomers of macropolyhedral borane ions [B20H18]n (n = 0, -2,
      -4).
AB  - Various isomers of macropolyhedral borane ions [B20H18]n (n = 0, -2, -4) are
      investigated by using the density functional theory methods at RB3LYP/6-31+G* and
      RB3LYP/6-31G* levels to obtain the optimized geometries, harmonic vibrational
      frequencies, electron structures, and the stability order. The calculated results
      show that optimized bond lengths are consistent with the available experimental
      values and the natural populations, taking [a2 -B20H18]4- (4) as an example, are
      also in agreement with NMR spectra. The calculated vibrational frequencies are
      all real, so all of these isomers could be stable, among which [a2 -B20H18]2- (3)
      and [a2 -B20H18]0 (7) are considered for the first time in this paper. On the
      basis of the contour maps of molecular orbitals, the delocalized characteristic
      of molecular orbitals and the possible redox mechanism of these ions are also
      discussed. Moreover, the analysis on counting of skeletal bonding electrons shows
      that the isomers (1)-(6) obey the electronic requirement predicted by the mno
      rule, whereas the newly predicted isomer (7) does not match the mno rule.

PMID- 16981236
TI  - Analysis of the segmented contraction of basis functions using density matrix
      theory.
AB  - A particular formulation based on density matrix (DM) theory at the Hartree-Fock
      level of theory and the description of the atomic orbitals as integral transforms
      is introduced. This formulation leads to a continuous representation of the
      density matrices as functions of a generator coordinate and to the possibility of
      plotting either the continuous or discrete density matrices as functions of the
      exponents of primitive Gaussian basis functions. The analysis of these diagrams
      provides useful information allowing: (a) the determination of the most important
      primitives for a given orbital, (b) the core-valence separation, and (c) support
      for the development of contracted basis sets by the segmented method.

PMID- 16981237
TI  - Importance of individual side chains for the stability of a protein fold:
      computational alanine scanning of the insulin monomer.
AB  - A new computational approach is proposed to probe the importance of residue side
      chains for the stability of a protein fold. Computational mutations to estimate
      protein stability (CMEPS) is based on the notion that the binding free energy
      corresponding to the complexation of a given side chain, considered as a "pseudo
      ligand" of the wild type protein, reflects the importance of this side chain to
      the thermodynamic stability of the protein. The contribution of a particular side
      chain to the folding energy is estimated according to the molecular mechanics
      generalized born surface area MM-GBSA approach, using a single molecular dynamics
      simulation trajectory of the wild type protein. CMEPS is a first principles
      method which does not contain any adjustable parameter that could be fitted to
      experimental data. The approach is first validated for Barnase and the B1 domain
      of protein L, for which a correlation coefficient R = 0.73, between experimental
      and CMEPS calculated DeltaDeltaG values, is found and then applied to the insulin
      monomer. In the present application, CMEPS replaces each amino acid by an alanine
      residue. Therefore, most mutations lead to cavities in the protein. From this the
      change in stability can be correlated with increased cavity volume. For insulin,
      this correlation is very similar compared with data previously analyzed for T4
      lysozyme from an experiment for buried apolar side chains. There, the increased
      cavity volume has been related to the hydrophobic effect. However, since CMEPS
      uses the energetics in terms of electrostatic and van der Waals interactions (and
      not the hydrophobic effect which is difficult to relate to physical
      interactions), it is possible to study the effect of mutations of polar and
      solvent accessible side chains. According to CMEPS, residues Leu A16, Tyr A19,
      Leu B11, Leu B15, and Arg B22 are most important for the stability of the
      monomeric insulin fold. This is in agreement with experimental data. As a
      consequence, mutation of these residues may lead to misfolded and inactive
      insulin analogues.

PMID- 16981238
TI  - TLR-2-mediated induction of vascular endothelial growth factor (VEGF) in
      cartilage in septic joint disease.
AB  - Bacterial arthritis is a progressive joint disease which includes rapid
      destruction of articular cartilage even after clearance of the causal factor. The
      resulting post-infectious arthropathy is mainly characterized by self
      perpetuating joint destruction and extensive angiogenesis in the emerging pannus
      like synovial membrane, but the underlying molecular mechanisms of the bacteria
      initiated process remain incompletely understood. This study was conducted to
      elucidate the expression and regulation of angiogenic and cartilage-destructive
      vascular endothelial growth factor (VEGF) in septic arthritis. For that purpose,
      aspirates of synovial fluid from patients with pyogenic arthritis were examined
      for VEGF levels by ELISA. In vitro studies with primary and immortalized
      chondrocytes were performed to determine whether Gram-positive and Gram-negative
      bacteria induce VEGF expression, by using real-time RT-PCR, ELISA, and
      immunohistochemistry. Activation of the transcription factor AP-1 was assessed by
      EMSA experiments. The necessity of the Toll-like receptor-2 (TLR-2), ERK-1/-2,
      and AP-1 pathway for infectious VEGF induction in chondrocytes was examined by
      using specific blocking reagents. ELISA experiments revealed that aspirates of
      synovial fluid from patients with pyogenic arthritis contain elevated levels of
      VEGF. The in vitro results confirmed the transcriptional induction of VEGF in
      chondrocytes after bacterial challenge by real-time RT-PCR, ELISA, and
      immunohistochemistry. This activation was mediated by a TLR-2-, ERK-1/-2-, and AP
      1-dependent pathway. The findings demonstrate the expression of Toll-like
      receptors on mesenchymal articular chondrocytes and reveal TLR-2-mediated VEGF
      induction in human chondrocytes after Gram-positive bacterial sensing. Since VEGF
      is a potent angiogenic and tissue remodelling factor, evidence that Toll-like
      receptors contribute to destructive arthropathy after microbial joint infection
      is provided. VEGF may be a therapeutic target in the future for the prevention of
      post-infectious cartilage degradation in articular joints.

PMID- 16981239
TI  - Delayed inflammatory responses to endotoxin in fibrinogen-deficient mice.
AB  - Severe inflammation leads to haemostatic abnormalities, such as the development
      of microvascular thrombi. As a result, ischaemia-related downstream organ damage
      can occur. The present study demonstrates that mice with a total deficiency of
      fibrinogen (Fg(-/-)) present with altered responses to challenge with Gram
      negative lipopolysaccharide (LPS). Early survival in response to continuous LPS
      challenge was increased in Fg(-/-) mice and histological findings indicated that
      this improvement correlated with a lack of fibrin deposition in organs.
      Neutrophils appeared early in the lungs of challenged wild-type (WT) mice, but
      occurred in Fg(-/-) mice at later times. This delayed response in Fg(-/-) mice
      was confirmed by studies that showed a strong dependence on Fg of binding of
      neutrophils to endothelial cells in the presence of LPS. While cytokines were
      also elevated in both WT and Fg(-/-) mice, their levels were generally lower at
      early times in this latter group. The time course of MIP-2 expression correlated
      with the occurrence of pulmonary leakage after LPS challenge, which was delayed
      in Fg(-/-) mice. These results suggest that fibrin(ogen) plays a role as an early
      mediator in the cross-talk between coagulation and inflammation.

PMID- 16981240
TI  - Assessment of novel inhibitors of Helicoverpa aminopeptidases as anti-insect
      agents.
AB  - Helicoverpa species present problems worldwide as pests on a variety of
      agricultural crops. In Australia, the costs of controlling H. armigera (Hubn.)
      and H. punctigera (Wall.) are a major burden on the cotton industry, and novel
      mechanisms are continually sought to combat these pests. Potential new targets
      for insecticides are the digestive proteases of the insect, including the
      aminopeptidases (APs). A variety of compounds, designed to be similar in
      structure to known AP inhibitors, were synthesized and screened for activity in
      inhibiting H. armigera larval growth and AP activity. The most effective
      compounds in both assays proved to be hydroxamic acids and methylphosphonic
      acids. Compounds that incorporated both of these groups were also found to have
      significant potential as control agents. The most inhibitory compounds included
      valine methylphosphonic acid and a leucine methylphosphonic acid/hydroxamic acid
      derivative. The valine methylphosphonic acid compound was tested further in
      vitro, with the aim of producing a new active capable of restricting the
      viability of Helicoverpa populations on commercial crops.

PMID- 16981241
TI  - Analysis of novel angiotensin-I-converting enzyme inhibitory peptides from
      protease-hydrolyzed marine shrimp Acetes chinensis.
AB  - Acetes chinensis is an underutilized shrimp species thriving in the Bo Hai Gulf
      of China. In a previous study, we had used the protease from Bacillus sp. SM98011
      to digest this kind of shrimp and found that the oligopeptide-enriched
      hydrolysate possessed antioxidant activity and high angiotensin I-converting
      enzyme (ACE) inhibitory activity with an IC50 value of 0.97 mg/ml. In this paper,
      by ultrafiltration, gel permeation chromatography and reversed-phase high
      performance liquid chromatography (RP-HPLC), five peptides with high ACE
      inhibitory activity were purified from the shrimp hydrolysates and their
      sequences were identified by amino acid composition analysis and molecular weight
      (MW) analysis. Three of them, FCVLRP (a), IFVPAF (f) and KPPETV (j), were novel
      ACE inhibitory peptides. Their IC50 values were 12.3 microM, 3.4 microM and 24.1
      microM, respectively, and their recoveries were 30 mg/100 g (solid basis of
      shrimp), 19 mg/100 g and 33 mg/100 g, respectively. Lineweaver-Burk plots for the
      three novel peptides showed that they are all competitive inhibitors. To test the
      ACE inhibitory activity of peptide a, f, j after they were digested by digestive
      enzymes in vivo, 12 derived peptides from FCVLRP and IFVPAF were synthesized
      based on their amino acid sequences and the cleavage sites of digestive enzymes.
      No digestive enzyme cleavage site was found in KPPETV. The IC50 values of the
      derived peptides were determined and the result showed that except for VPAF, FC
      and FCVL, the ACE inhibitory activity of the other nine derived peptides did not
      significantly change when compared with their original peptides. Surprisingly,
      five peptides had lower IC50 values than their original peptides, particularly
      for RP (IC50 value = 0.39 microM), which is about 30 times lower than its
      original peptide and almost the lowest IC50 value for ACE inhibitory peptides
      reported. Therefore, the novel peptides identified from A. chinensis hydrolysates
      probably still maintain a high ACE inhibitory activity even if they are digested
      in vivo. This is the first report about novel ACE inhibitory peptides from
      hydrolysates of marine shrimp A. chinensis. The novel peptides from hydrolysate
      of A. chinensis and some of their derived peptides with high ACE inhibitory
      activity probably have potential in the treatment of hypertension or in clinical
      nutrition.

PMID- 16981242
TI  - Novel alpha-conotoxins identified by gene sequencing from cone snails native to
      Hainan, and their sequence diversity.
AB  - Conotoxins (CTX) from the venom of marine cone snails (genus Conus) represent
      large families of proteins, which show a similar precursor organization with
      surprisingly conserved signal sequence of the precursor peptides, but highly
      diverse pharmacological activities. By using the conserved sequences found within
      the genes that encode the alpha-conotoxin precursors, a technique based on RT-PCR
      was used to identify, respectively, two novel peptides (LiC22, LeD2) from the two
      worm-hunting Conus species Conus lividus, and Conus litteratus, and one novel
      peptide (TeA21) from the snail-hunting Conus species Conus textile, all native to
      Hainan in China. The three peptides share an alpha4/7 subfamily alpha-conotoxins
      common cysteine pattern (CCX(4)CX(7)C, two disulfide bonds), which are
      competitive antagonists of nicotinic acetylcholine receptor (nAChRs). The cDNA of
      LiC22N encodes a precursor of 40 residues, including a propeptide of 19 residues
      and a mature peptide of 21 residues. The cDNA of LeD2N encodes a precursor of 41
      residues, including a propeptide of 21 residues and a mature peptide of 16
      residues with three additional Gly residues. The cDNA of TeA21N encodes a
      precursor of 38 residues, including a propeptide of 20 residues and a mature
      peptide of 17 residues with an additional residue Gly. The additional residue Gly
      of LeD2N and TeA21N is a prerequisite for the amidation of the preceding C
      terminal Cys. All three sequences are processed at the common signal site -X-Arg-
      immediately before the mature peptide sequences. The properties of the alpha4/7
      conotoxins known so far were discussed in detail. Phylogenetic analysis of the
      new conotoxins in the present study and the published homologue of alpha4/7
      conotoxins from the other Conus species were performed systematically. Patterns
      of sequence divergence for the three regions of signal, proregion, and mature
      peptides, both nucleotide acids and residue substitutions in DNA and peptide
      levels, as well as Cys codon usage were analyzed, which suggest how these
      separate branches originated. Percent identities of the DNA and amino acid
      sequences of the signal region exhibited high conservation, whereas the sequences
      of the mature peptides ranged from almost identical to highly divergent between
      inter- and intra-species. Notably, the diversity of the proregion was also high,
      with an intermediate percentage of divergence between that observed in the signal
      and in the toxin regions. The data presented are new and are of importance, and
      should attract the interest of researchers in this field. The elucidated cDNAs of
      these toxins will facilitate a better understanding of the relationship of their
      structure and function, as well as the process of their evolutionary
      relationships.

PMID- 16981243
TI  - Renal prothrombin mRNA is significantly decreased in a hyperoxaluric rat model of
      nephrolithiasis.
AB  - Although urinary prothrombin fragment 1 (UPTF1) possesses several hallmarks
      expected of a regulatory protein in urolithiasis, its precise role remains
      unknown. To determine the relationship between renal prothrombin (PT), the parent
      molecule of UPTF1, and lithogenesis, this study quantified and compared levels of
      renal PT mRNA in healthy rats (n = 10) and rats rendered lithogenic (n = 10) by
      ingestion of 0.75% ethylene glycol for 8 weeks. Studies included morphological
      and histological examination of the kidneys with scanning electron microscopy of
      the urinary filtrates of control and experimental animals. Haematuria and calcium
      oxalate (CaOx) crystals occurred in the urine of all experimental rats, but not
      in those of controls. Histological examination showed birefringent nephroliths
      and associated damage in kidneys of lithogenic rats, which were not seen in the
      control group. The amounts of total RNA extracted from both groups of rats were
      similar, but the median ratio of PT to beta-actin transcript of 11.14 x 10(-4)
      (10.65 x 10(-4) +/- 2.24 x 10(-4)) in the control rats was significantly (p < or
      = 0.001) reduced to 6.47 x 10(-4) (6.57 x 10(-4) +/- 2.72 x 10(-4)) in the
      lithogenic group. These results demonstrate that renal PT mRNA is reduced by
      approximately 42% in lithogenic rats and confirm the existence of a direct
      association between renal PT synthesis and calculogenesis. Attempts to compare
      renal PT and urinary levels of PTF1 were unsuccessful because of interference
      from hepatic PT circulating in the blood, haematuria, and the presence of urinary
      CaOx crystals. This is the first report of a significant reduction in the renal
      expression of a urinary protein well documented to inhibit CaOx crystal growth
      and aggregation in undiluted human urine in vitro.

PMID- 16981245
TI  - C/EBPbeta is over-expressed in gastric carcinogenesis and is associated with COX
      2 expression.
AB  - The CCAAT/enhancer-binding protein beta (C/EBPbeta) transcription factor has been
      associated with several cancer models. In this study, the expression of C/EBPbeta
      was analysed in a series of 90 gastric carcinomas (GCs). We also assessed the
      effect of C/EBPbeta on COX-2 expression. In normal gastric mucosa, C/EBPbeta
      expression was restricted to cells in the proliferative zone. In intestinal
      metaplasia, dysplasia, and GC of the intestinal and atypical subtypes, C/EBPbeta
      was over-expressed (p < 0.0001, for the association with histological type).
      C/EBPbeta and Ki67, a marker of cell proliferation, were also co-expressed in
      primary GC. We also observed an overlap between C/EBPbeta and COX-2 expression in
      GC. Using GC cell lines we show that C/EBPbeta can regulate the expression of
      endogenous COX-2 and transactivate the promoter of the COX-2 gene, depending on
      its methylation status. These results suggest that C/EBPbeta may be a marker of
      neoplastic transformation and also play an active role in gastric tumourigenesis
      by regulating COX-2 expression.

PMID- 16981244
TI  - Evolution of VHL tumourigenesis in nerve root tissue.
AB  - Haemangioblastomas are the key central nervous system manifestation of von Hippel
      Lindau (VHL) disease, which is caused by germline mutation of the VHL gene. We
      have recently shown that 'tumour-free' spinal cord from patients with VHL disease
      contains microscopic, poorly differentiated cellular aggregates in nerve root
      tissue, which we descriptively designated 'mesenchymal tumourlets'. Here we have
      investigated spinal cord tissue affected by multiple tumours. We show that a
      small subset of mesenchymal tumourlets extends beyond the nerve root to form
      proliferative VHL-deficient mesenchyme and frank haemangioblastoma. We thus
      demonstrate that tumourlets present potential, but true precursor material for
      haemangioblastoma. We further show that intraradicular tumourlets consist of
      scattered VHL-deficient cells with activation of HIF-2alpha and HIF-dependent
      target proteins including CAIX and VEGF, and are associated with an extensive
      angiogenic response. In contrast, activation of HIF-1alpha was only observed in
      the later stages of tumour progression. In addition, ultrastructural examination
      reveals gradual transition from poorly differentiated VHL-deficient cells into
      vacuolated cells with a 'stromal' cell phenotype. The evolution of frank
      haemangioblastoma seems to involve multiple steps from a large pool of precursor
      lesions.

PMID- 16981246
TI  - Spatial and acoustic pressure dependence of microbubble-mediated gene delivery
      targeted using focused ultrasound.
AB  - BACKGROUND: Ultrasound/microbubble-mediated gene delivery has the potential to be
      targeted to tissue deep in the body by directing the ultrasound beam following
      vector administration. Application of this technology would be minimally invasive
      and benefit from the widespread clinical experience of using ultrasound and
      microbubble contrast agents. In this study we evaluate the targeting ability and
      spatial distribution of gene delivery using focused ultrasound. METHODS: Using a
      custom-built exposure tank, Chinese hamster ovary cells in the presence of
      SonoVue microbubbles and plasmid encoding beta-galactosidase were exposed to
      ultrasound in the focal plane of a 1 MHz transducer. Gene delivery and cell
      viability were subsequently assessed. Characterisation of the acoustic field and
      high-resolution spatial analysis of transfection were used to examine the
      relationship between gene delivery efficiency and acoustic pressure. RESULTS: In
      contrast to that seen in the homogeneous field close to the transducer face, gene
      delivery in the focal plane was concentrated on the ultrasound beam axis. Above a
      minimum peak-to-peak value of 0.1 MPa, transfection efficiency increased as
      acoustic pressure increased towards the focus, reaching a maximum above 1 MPa.
      Delivery was microbubble-dependent and cell viability was maintained.
      CONCLUSIONS: Gene delivery can be targeted using focused ultrasound and
      microbubbles. Since delivery is dependent on acoustic pressure, the degree of
      targeting can be determined by appropriate transducer design to modify the
      ultrasound field. In contrast to other physical gene delivery approaches, the non
      invasive targeting ability of ultrasound makes this technology an attractive
      option for clinical gene therapy.

PMID- 16981247
TI  - A peptide-based immunoassay for antibodies against botulinum neurotoxin A.
AB  - Cervical dystonia (CD) is due to neck-muscle spasms that cause pain and
      involuntary contractions resulting in abnormal neck movements and posture.
      Symptoms can be relieved by injecting the affected muscle with a botulinum
      neurotoxin (BoNT, usually type A or type B). The therapeutic benefits are
      impermanent and toxin injections need to be repeated every 3-6 months. In a very
      small percentage of patients (less with BoNT/A than with BoNT/B) the treatment
      elicits blocking anti-toxin antibodies (Abs), which reduce or terminate the
      patient's responsiveness to further treatment. We have recently mapped (Dolimbek
      et al., 2006) the CD sera Ab-binding profile using a panel of 60, 19-residue
      peptides that encompassed the entire H chain sequence 449-1296 and overlapped
      consecutively by 5 residues. Abs in CD sera bound to one or more of the peptides
      N25, C10, C15, C20, and C31. This suggested the possibility that binding to these
      peptides could be used for assay of Abs in CD sera. Data analysis reported here
      found that Ab binding to these regions showed very significant deviations from
      the control responses. Of these four peptides, C10 showed the most significant
      level of separation between patient and control groups (p = 5 x 10(-7)) and the
      theoretical resolution (i.e., ability to distinguish CD patients from control,
      see full definition under 'Statistical analysis' in Methods), 84%, was about 4%
      higher than the least resolved response, C31 (p = 6 x 10(-6), resolution 80%).
      Since the amounts of Abs bound to a given peptide varied with the patient and not
      all the patients necessarily recognized all four peptides, there was the
      possibility that binding to combinations of two or more peptides might give a
      better discriminatory capability. Using two peptides, C10 plus C31, the
      resolution improved to 87% (p = 4 x 10(-8)). These two peptides appeared to
      compliment each other and negate the lower resolution of C31. Combination of
      three peptides gave resolutions that ranged from 85 (N25 + C15 + C31; p = 2 x 10(
      7)) to 88% (C10 + C15 + C31; p = 1 x 10(-8)). Finally, using the data of all four
      peptides, N25 + C10 + C15 + C31, gave a resolution of 86% (p = 1 x 10(-7)).
      Although these levels of resolution are somewhat lower than that obtained with
      whole BoNT/A (resolution 97%; p = 6 x 10(-12)), it may be concluded that the two
      peptide combination C10 + C31, or the three-peptide combination C10 + C15 + C31
      (affording resolutions of 87 and 88%, respectively) provide a good diagnostic,
      toxin-free procedure for assay of total specific anti-toxin Abs in BoNT/A-treated
      CD patients.

PMID- 16981248
TI  - Comparison of efficacy, absorption and translocation of three glyphosate
      formulations on velvetleaf (Abutilon theophrasti).
AB  - Growth analysis, absorption and translocation studies were conducted to compare a
      1-aminomethanamide dihydrogen tetraoxosulfate (GLY-A) formulation of glyphosate
      with two isopropylamine (GLY-IPA-1, GLY-IPA-2) formulations of glyphosate on
      velvetleaf. The two isopropylamine formulations differed by the presence of a
      surfactant in the formulation, GLY-IPA-1 containing surfactant whereas GLY-IPA-2
      did not. Four- to six-leaf velvetleaf was treated with GLY-A and GLY-IPA-1 and
      GLY-IPA-2 (0, 50, 67, 89, 119, 158, 280, 420, 560 and 840 g AE ha(-1)) with and
      without ammonium sulfate (AMS; 20 g L(-1)). GLY-A and GLY-IPA-2 included a non
      ionic surfactant (2.5 mL L(-1)) in the spray solution at all herbicide
      concentrations. No additional surfactant was added to GLY-IPA-1. The IC50 value
      for GLY-A was 88 g AE ha(-1) compared with 346 and 376 g AE ha(-1) for GLY-IPA-1
      and GLY-IPA-2 respectively in the absence of AMS. When AMS (20 g L(-1)) was added
      to the spray solution, the estimated IC50 values were 143, 76 and 60 g AE ha(-1)
      for GLY-IPA-1, GLY-IPA-2 and GLY-A respectively. Absorption of 14C-glyphosate
      into the third leaf of five- to six-leaf velvetleaf was three- to sixfold greater
      72 h after treatment (HAT) when applied as GLY-A compared with GLY-IPA-1 and GLY
      IPA-2 respectively in the absence of AMS. AMS (20 g L(-1)) increased absorption
      of 14C-glyphosate in all glyphosate formulations two- to threefold, but
      differences among the formulations remained. Approximately three- and sixfold
      more 14C-glyphosate applied as GLY-A had translocated out of the treated leaf
      compared with GLY-IPA-1 and GLY-IPA-2 respectively by 72 HAT. Adding AMS (20 g L(
      1)) increased translocation of 14C-glyphosate out of the treated leaf
      approximately 2.5-fold for all three formulations. The increased efficacy of GLY
      A versus GLY-IPA-1 and GLY-IPA-2 on velvetleaf is due to the greater rate of
      absorption and subsequent translocation of glyphosate out of the treated leaf.
      AMS increased the efficacy of all three formulations by increasing absorption and
      translocation of glyphosate in the plant.

PMID- 16981249
TI  - Use of models to assess the reduction in contamination of water bodies by
      agricultural pesticides through the implementation of policy instruments: A case
      study of the Voluntary Initiative in the UK.
AB  - Through normal agricultural use, pesticides may reach environmental water bodies
      via several routes of entry. Various policies and initiatives exist to reduce the
      effects of pesticides in the environment. One such initiative in place in the UK
      is the Voluntary Initiative (VI). The VI is a voluntary scheme put forward by the
      Crop Protection Association with other crop protection and farming organisations
      to reduce the environmental impacts of pesticides. Mathematical models of
      pesticide fate can usefully be applied to examine the impact of factors
      influencing the contamination of water bodies by pesticides. The work reported
      here used water quality models to examine how changes in farmer behaviour could
      potentially impact pesticide contamination of environmental water bodies. As far
      as possible, uncalibrated, standard regulatory models were used. Where suitable
      models were not available, simple models were defined for the purposes of the
      study and calibrated using literature data. Scenarios were developed to represent
      different standards of practice with respect to pesticide user behaviour. The
      development of these scenarios was guided by the Crop Protection Management Plan
      (CPMP) aspect of the VI. A framework for the use of modelling in the evaluation
      of the VI is proposed. The results of the modelling study suggest that, in
      several areas, widespread adoption of the measures proposed in the VI could lead
      to reductions in pesticide contamination of environmental water bodies. These
      areas include pesticide contamination from farmyards, spray drift and field
      runoff. In other areas (including pesticide leaching to groundwater and
      contamination of surface water from field drains) the benefits that may
      potentially be gained from the VI are less clear. A framework to evaluate the VI
      should take into consideration the following aspects: (1) groundwater is more at
      risk when there is a combination of leachable compounds, vulnerable soils,
      shallow groundwater and high product usage; (2) surface water contamination from
      drains is most likely when heavy rain falls soon after application, the soils are
      vulnerable and product usage is high; (3) surface water contamination from drift
      is most likely when the distance between the spray boom and water body is small
      and product usage is high; (4) surface water contamination from farmyards is
      dependent on the nature of the farmyard surface, the competence of the spray
      operator and the level of product usage. Any policy or initiative to reduce
      pesticide contamination should be measured against farmer behaviour in these
      areas.

PMID- 16981250
TI  - Influence of Portland cement amendment on soil pH and residual soil termiticide
      performance.
AB  - Soil adjacent to new brick veneer work is likely to have a higher pH owing to the
      mixture of cement with the soil. In the Gainesville, FL, area, soil samples taken
      from such locations had a range of pH values from 9.0 to 10.1; similar soils used
      in bioassays had a pH of 5.6 before the addition of cement. Addition of 15 mg of
      Portland cement to 33 g of soil increased the pH to 6, and addition of 291 mg of
      Portland cement increased the pH to 9. The pH of soil amended with cement was
      stable for the first 5 months. After 10 months, soil pH values decreased from
      alkaline to near neutral in all cases. Eastern subterranean termite workers,
      Reticulitermes flavipes (Kollar), were exposed to the treated soil at pH 6-9 for
      24 h, and percentage mortality was recorded at 5 days, 5 months and 10 months.
      Termite mortality significantly decreased at higher soil pHs for bifenthrin,
      chlorpyrifos, fipronil and imidacloprid treatments at 5 months and similarly for
      bifenthrin, permethrin, chlorpyrifos, fipronil and imidacloprid treatments at 10
      months. There was an inverse linear relationship between soil pH and mortality.
      Increased soil pH diminished residual activity of termiticide in the following
      order: imidacloprid > fipronil > chlorpyrifos = bifenthrin > permethrin >
      cypermethrin.

PMID- 16981251
TI  - Characterization and over-expression of chaperonin t-complex proteins in
      colorectal cancer.
AB  - The chaperonins are key molecular complexes, which are essential in the folding
      of proteins to produce stable and functionally competent protein conformations.
      One member of the chaperonin group of proteins is TCP1 (chaperonin containing t
      complex polypeptide 1, or CCT), but little is known about this protein in
      tumours. In this study, we used comparative proteomic analysis to show that t
      complex protein subunits TCP1 beta and TCP1 epsilon are over-expressed in
      colorectal adenocarcinomas. Monoclonal antibodies to these proteins were
      developed and the expression and cellular localization of these two proteins in
      colorectal cancer were analysed by immunohistochemistry on a colorectal cancer
      tissue microarray. In colorectal cancer, TCP1 beta cellular localization was
      exclusively cytoplasmic, whereas TCP1 epsilon staining was seen in both the
      nucleus and the cytoplasm. Both cytoplasmic TCP1 beta and cytoplasmic TCP1
      epsilon were significantly over-expressed (p < 0.001 for each protein) in primary
      colorectal cancer and also showed increased expression with advancing Dukes'
      stage (p = 0.018 for TCP1 beta and p = 0.045 for TCP1 epsilon). A trend was also
      identified between over-expression of cytoplasmic TCP1 beta and reduced patient
      survival (p = 0.05). These results show that both TCP1 beta and TCP1 epsilon are
      over-expressed in colorectal cancer and indicate a role for TCP1 beta and TCP1
      epsilon in colorectal cancer progression.

PMID- 16981252
TI  - Low expression of HER2 protein in breast cancer is biologically significant.
AB  - HER2 status is routinely tested using immunohistochemistry or FISH following the
      licensing of a therapeutic agent targeting HER2. However, neither of these
      methods provides quantitative information relating to the 70-80% of patients with
      levels of expression lower than the assay detection thresholds. In this study,
      radioimmunohistochemistry was used to detect quantitative HER2 protein expression
      in 178 breast cancers. Survival analysis was performed, as were correlations with
      known prognostic variables and with overexpression of other HER family members.
      It is demonstrated that the populations expressing very high and very low levels
      of HER2 are each associated with increased risk of cancer-specific death on
      survival analysis (p = 0.0043). The group with low levels of HER2 was more likely
      to be of higher grade, EGFR-positive and ER/HER3/HER4-negative. HER2-positive
      cases were frequently ER-negative/HER3-positive, whilst cases with normal HER2
      expression were often ER-positive/HER4-positive. The aggressive nature of the
      tumour group with low HER2 expression may be explained by actions of other HER
      family members, particularly EGFR, but whether these or other factors have a
      negative regulatory effect on HER2 expression remains to be determined.

PMID- 16981253
TI  - Epigenetic effects of ethanol on liver and gastrointestinal injury.
AB  - Alcohol consumption causes cellular injury. Recent developments indicate that
      ethanol induces epigenetic alterations, particularly acetylation, methylation of
      histones, and hypo- and hypermethylation of DNA. This has opened up a new area of
      interest in ethanol research and is providing novel insight into actions of
      ethanol at the nucleosomal level in relation to gene expression and patho
      physiological consequences. The epigenetic effects are mainly attributable to
      ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative
      metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic
      changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma
      and gastrointestinal injury. This editorial highlights these new advances and its
      future potential.

PMID- 16981254
TI  - Screening in liver disease.
AB  - A disease is suitable for screening if it is common, if the target population can
      be identified and reached and if both a good screening test and an effective
      therapy are available. Of the most common liver diseases only viral hepatitis and
      genetic hemochromatosis partially satisfy these conditions. Hepatitis C is
      common, the screening test is good and the therapy eliminates the virus in half
      of the cases, but problems arise in the definition of the target population. In
      fact generalized population screening is not endorsed by international
      guidelines, although some recommend screening immigrants from high prevalence
      countries. Opportunistic screening (case finding) of individuals with classic
      risk factors, such as transfusion before 1992 and drug addiction, is the most
      frequently used strategy, but there is disagreement whether prison inmates,
      individuals with a history of promiscuous or traumatic sex and health care
      workers should be screened. In a real practice setting the performance of
      opportunistic screening by general practitioners is low but can be ameliorated by
      training programs. Screening targeted to segments of the population or mass
      campaigns are expensive and therefore interventions should be aimed to improve
      opportunistic screening and the detection skills of general practitioners.
      Regarding genetic hemochromatosis there is insufficient evidence for population
      screening, but individual physicians can decide to screen racial groups with a
      high prevalence of the disease, such as people in early middle age and of
      northern European origin. In the other cases opportunistic screening of high risk
      individuals should be performed, with a high level of suspicion in case of
      unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and
      skin pigmentation.

PMID- 16981255
TI  - Mutation screening of mismatch repair gene Mlh3 in familial esophageal cancer.
AB  - AIM: To shed light on the possible role of mismatch repair gene Mlh3 in familial
      esophageal cancer (FEC). METHODS: A total of 66 members from 10 families
      suggestive of a genetic predisposition to hereditary esophageal cancer were
      screened for germline mutations in Mlh3 with denaturing high performance liquid
      chromatography (DHPLC), a newly developed method of comparative sequencing based
      on heteroduplex detection. For all samples exhibiting abnormal DHPLC profiles,
      sequence changes were evaluated by cycle sequencing. For any mutation in family
      members, we conducted a segregation study to compare its prevalence in sporadic
      esophageal cancer patients and normal controls. RESULTS: Exons of Mlh3 in all
      samples were successfully examined. Overall, 4 missense mutations and 3
      polymorphisms were identified in 4 families. Mlh3 missense mutations in families
      9 and 10 might be pathogenic, but had a reduced penetrance. While in families 1
      and 7, there was no sufficient evidence supporting the monogenic explanations of
      esophageal cancers in families. The mutations were found in 33% of high-risk
      families and 50% of low-risk families. CONCLUSION: Mlh3 is a high risk gene with
      a reduced penetrance in some families. However, it acts as a low risk gene for
      esophageal cancer in most families. Mutations of Mlh3 may work together with
      other genes in an accumulated manner and result in an increased risk of
      esophageal tumor. DHPLC is a robust and sensitive technique for screening gene
      mutations.

PMID- 16981256
TI  - Gene therapy that inhibits NF-kappaB results in apoptosis of human
      hepatocarcinoma by recombinant adenovirus.
AB  - AIM: To investigate whether the recombinant adenovirus induces the TNF-alpha
      mediated apoptosis in vivo. METHODS: Human hepatocarcinoma cell line (HepG(2))
      cells were transfected into BALB/c nude mice, and the tumor growth curve was
      drawn. We analyzed apoptosis in HepG(2) cells by TUNEL, HE staining and electron
      microscopy. RESULTS: AdIkappaBalphaM was expressed stably and efficiently in
      HepG(2) and could not be degraded by induction of TNF-alpha. Tumor growth in mice
      could be reduced remarkably if treated by AdIkappaBalphaM plus TNF-alpha. There
      was apoptosis of > 70% of cells treated with AdIkappaBalphaM plus TNF-alpha and
      about 50% of cells treated with AdIkappaBalphaM. In contrast, there was few cell
      apoptosis in HepG(2) cells treated with phosphate buffered saline and
      AdIkappaBalpha. HepG(2) cells in mice also exhibited a high level of apoptosis
      after in vivo injection with AdIkappaBalphaM. The tumor growth curve indicated
      the tumor transfected with AdIkappaBalphaM could be restrained. CONCLUSION:
      AdIkappaBalphaM gene therapy greatly enhances apoptosis due to inhibition of an
      NF-kappaB-mediated antiapoptosis signaling pathway.

PMID- 16981257
TI  - Triple antiviral therapy in HCV positive patients who failed prior combination
      therapy.
AB  - AIM: To assess the efficacy of triple therapy (peginte-rferon or high dose
      standard interferon, plus ribavirin and amantadine) in nonresponders to prior
      combination therapy. METHODS: A total of 196 patients were enrolled in a
      multicenter, open, randomized study. Patients were given 180 mug/wk of
      peginterferon-alpha-2a (40 kDa) plus ribavirin (800-1000 mg/d) and amantadine
      (200 mg/d) for 48 wk (group A) or interferon-alpha-2a (6 MU/d for 4 wk, 3 MU/d
      for 20 wk, and 3 MU tiw for 24 wk) plus ribavirin (800-1000 mg/d) and amantadine
      (200 mg/d) for 48 wk (group B). RESULTS: Overall sustained virologic response
      (SVR) was 26.6% (32.1% and 19.5% in group A and B, P = 0.057). Baseline ALT > 120
      UI/L (OR 2.4; 95% CI: 1.11 to 5.20; P = 0.026) and HCV RNA negativity after 12 wk
      (OR 8.7; 95% CI: 3.87 to 19.74; P < 0.0001) were independently associated with
      SVR. Therapy discontinuation occurred less frequently in patients treated with
      peginterferon than standard interferon (P = 0.036). CONCLUSION: More than 25% of
      nonresponders to combination therapy can eradicate HCV infection when retreated
      with triple therapy, especially if they have a high baseline ALT and are treated
      with pegylated interferon.

PMID- 16981258
TI  - Detection of YMDD mutation using mutant-specific primers in chronic hepatitis B
      patients before and after lamivudine treatment.
AB  - AIM: To develop a PCR assay using mutant-specific primers to detect mutation of
      tyrosine-methionine-aspartate-aspartate (YMDD) motif of HBV to tyrosine-valine
      aspartate-aspartate (YVDD) or tyrosine-isoleucine-aspartate-aspartate (YIDD).
      METHODS: Cloned wild-type and mutant HBV sequences were used as templates to test
      the sensitivity and specificity of the assay. A variety of primer construction,
      primer concentration, dNTP concentration, and annealing temperature of primers
      were systematically examined. Pair primers specific to rtL180M and rtM204V were
      selected for YVDD detection. Primer specific to rtM204I with an additional 3'
      penultimate base mismatched to both the mutant and wild-type sequence was
      selected for YIDD detection. We applied this assay to study YMDD mutants in 28
      chronic hepatitis B patients before and after lamivudine treatment. RESULTS: We
      could detect as little as 0.001%-0.00001% of mutant viruses coexisting in 10(8)
      10(9) copies of wild-type HBV using this assay. YMDD mutants were detected in 8
      of 12 HBeAg-positive patients and 8 of 16 HBeAg-negative patients before
      lamivudine treatment. After treatment, two more patients in HBeAg-positive
      patients and seven more patients in HBeAg-negative patients developed YMDD
      mutations. CONCLUSION: We developed a highly sensitive and specific assay for
      detecting YMDD mutants. This assay can be applied to monitor chronic hepatitis B
      patients before and during lamivudine treatment.

PMID- 16981259
TI  - H. pylori receptor MHC class II contributes to the dynamic gastric epithelial
      apoptotic response.
AB  - AIM: To investigate the role of MHC class II in the modulation of gastric
      epithelial cell apoptosis induced by H pylori infection. METHODS: After
      stimulating a human gastric epithelial cell line with bacteria or agonist
      antibodies specific for MHC class II and CD95, the quantitation of apoptotic and
      anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD
      recruitment, was performed with a fluorometric assay, a cytometric bead array,
      and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with
      the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase
      activation at 24 h of H pylori infection. When caspase 3 activation was
      specifically measured, crosslinking of MHC class II resulted in a marked reduced
      caspase activation, while simple ligation of MHC class II did not. Crosslinking
      of MHC class II also resulted in an increased activation of the anti-apoptosis
      molecule BCL-2 compared to simple ligation. Confocal microscope analysis
      demonstrated that the pretreatment of gastric epithelial cells with a
      crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell
      surface. CONCLUSION: The results presented here demonstrate that the ability of
      MHC class II to modulate gastric epithelial apoptosis is at least partially
      dependent on its crosslinking. Furthermore, while previous research has
      demonstrated that MHC class II signaling can be pro-apoptotic during extended
      ligation, we have shown that the crosslinking of this molecule has anti-apoptotic
      effects during the earlier time points of H pylori infection. This effect is
      possibly mediated by the ability of MHC class II to modulate the activation of
      the pro-apoptotic receptor Fas by blocking the recruitment of the accessory
      molecule FADD, and this delay in apoptosis induction could allow for prolonged
      cytokine secretion by H pylori-infected gastric epithelial cells.

PMID- 16981260
TI  - First-line eradication of H pylori infection in Europe: a meta-analysis based on
      congress abstracts, 1997-2004.
AB  - AIM: To meta-analyse the European abstracts presented between 1997-2004 at the
      European H pylori Study Group, United European Gastroenterology Week meetings and
      World Congresses of Gastroenterology. METHODS: The abstracts of
      randomized/controlled prospective studies were classified into groups based on
      first-line eradication schedules. The quality of the abstracts was checked by a
      validated score system. The pooled eradication rates (PER) and combined odds
      ratios (OR) were calculated and compared with the published meta-analyses.
      RESULTS: The PER of proton pump inhibitor-based (PPI) one week triple therapies
      was 81.4% (confidence interval, 95% CI: 78.5-84.5). Ranitidine bismuth citrate
      based (RBC) triple regimens have an efficiency rate of 78.5% (95% CI: 70.5%
      84.3%) (P = 0.28 vs PPI). The OR for PPI effect vs RBC regimens was 1.1 (95% CI:
      0.92-1.30). H(2) receptor antagonist-based triple therapies achieved 64.1% (95%
      CI: 52.6-75.6) (P = 0.02 < 0.05 vs PPI), the OR vs PPI regimens was 1.55 (95% CI:
      0.72-3.78). PPI-based double combinations were less efficient than triple
      regimens (PER: 55.0%, OR: 4.90, 95% CI: 2.36-9.70). Quadruple regimens were
      successful in 82.6% (95% CI: 76.0-89.7), the OR vs triple therapies was 0.80
      (0.62-1.03). Clarithromycin + amoxicillin or nitroimidazole combinations were
      efficient in 80.5% (95% CI: 77.2-84.2) and 83.8% (95% CI: 81.7-85.9),
      respectively. Amoxicillin + nitromidazole therapies eradicated the infection in
      73.5% (66.6-78.5) (P = 0.01 < 0.05 vs clarithromycin-based regimens). CONCLUSION:
      PPI/RBC-based triple therapies achieved comparable results with the meta
      analyses. H(2)-receptor antagonists and PPI-based double combinations were less
      efficient. Triple and quadruple regimens were equally effective. Clarithromycin +
      either amoxicillin or nitroimidazole containing regimens were more effective than
      amoxicillin + nitroimidazole combinations. High quality congress abstracts
      constitutes a valuable pool of data which is suitable for meta-analytical workup.

PMID- 16981261
TI  - Taurolithocholate impairs bile canalicular motility and canalicular bile
      secretion in isolated rat hepatocyte couplets.
AB  - AIM: To investigate the effects of taurolithocholate (TLC) on the canalicular
      motility in isolated rat hepatocyte couplets (IRHC). METHODS: TLC was added to
      IRHC at concentrations of 10 and 50 mumol/L, respectively. In each group, five
      time-lapse movies containing 3 representative bile canaliculi were taken under
      phase-contrast microscopy for 12 h. The number of bile canalicular contractions
      and the intervals between consecutive canalicular contractions were calculated.
      Furthermore, the effects of TLC on IRHC were examined by transmission electron
      microscopy. RESULTS: The bile canalicular contractions were spontaneous and
      forceful in the controls. Active vesicular movement was observed in the
      pericanalicular region. Immediately after the addition of TLC, the bile
      canaliculi were deformed, and canalicular bile was incorporated into the
      vacuoles. The canaliculi were gradually dilated, and canalicular contractions
      were markedly inhibited by TLC. The vesicular movements became extremely slow in
      the pericanalicular region. The number of canalicular contractions significantly
      decreased in the TLC-treated groups, as compared with that in the controls. The
      time intervals were prolonged, as the TLC dosage increased, indicating that bile
      secretion into the canaliculi was impaired with TLC. Transmission electron
      microscopy revealed the lamellar transformation of the canalicular membranes in
      IRHC treated with TLC. CONCLUSION: TLC impairs both the bile canalicular
      contractions and the canalicular bile secretion, possibly by acting directly on
      the canalicular membranes in TLC-induced cholestasis.

PMID- 16981262
TI  - Evaluation of IGL-1 preservation solution using an orthotopic liver
      transplantation model.
AB  - AIM: To compare, in a pig liver transplantation model, the protective effect of
      UW with that of IGL-1, a high-sodium preservation solution containing
      polyethylene glycol (PEG) as an oncotic supply. METHODS: All livers were
      harvested and grafted orthotopically according to standard techniques. The livers
      were washed out and preserved for 7 h in IGL-1 (n = 6) or in UW solution (n = 7)
      at 4 degree centigrade. In a sham group (n = 4), the livers underwent a 60-min
      warm ischemia at 37 degree centigrade. The hepatocellular injury was assessed in
      organ preservation solution washed out from the graft at the end of ischemic
      storage (before revascularization), and in serum 2 h after reperfusion and daily
      for up to 6 d. RESULTS: Livers preserved in IGL-1 solution released markedly less
      AST than that preserved in the UW solution before and after revascularization (P
      < 0.05). Besides, the activity of creatine kinase-BB, a marker of sinusoidal
      lining cells injury, was higher in the UW group than in the IGL-1 group (P <
      0.05). Histological results showed less necrotic regions in livers preserved in
      IGL-1 solution; however, no difference was observed for inflammation. CONCLUSION:
      IGL-1 liquid effectively protects parenchymal and non-parenchymal cells against
      preservation-reperfusion injuries.

PMID- 16981263
TI  - Kinase domain insert containing receptor promoter controlled suicide gene system
      selectively kills human umbilical vein endothelial cells.
AB  - AIM: To study the selective killing of human umbilical vein endothelial cells
      (HUVECs) by a double suicide gene under the regulation of a kinase domain insert
      containing receptor (KDR) promoter and mediated by an adenoviral gene vector.
      METHODS: Human KDR promoter was cloned by polymerase chain reaction (PCR), and
      two recombinant adenoviral plasmids pAdKDR-CdglyTK, pAdCMV-CDglyTK were
      constructed according to a two-step transformation protocol. These two newly
      constructed plasmids were then transfected into 293 packaging cells to grow
      adenovirus, which were further multiplied and purified. HUVECs and LoVo cells
      were infected with either of the two resultant recombinant adenoviruses (AdKDR
      CDglyTK and AdCMV-CDglyTK) respectively, and the infection rates were estimated
      by detection of green fluorescent protein (GFP) expression. Infected cells were
      cultured in culture media containing different concentrations of 5-fluorocytosine
      (5-FC) and ganciclovir (GCV), and the killing effects were measured. RESULTS: The
      two recombinant adenoviral plasmids pAdKDR-CdglyTK, pAdCMV-CDglyTK were
      successfully constructed and transfected into 293 cells. The resultant
      recombinant adenoviruses infected cells caused similar infection rates; and the
      infected cells exhibited different sensitivity to the prodrugs: HUVECs infected
      with AdCMV-CDglyTK and LoVo cells infected with AdCMV-CDglyTK were highly
      sensitive to the prodrugs, and HUVECs infected with AdKDR-CDglyTK were similarly
      sensitive but significantly more sensitive than the LoVo cells infected with
      AdKDR-CdglyTK (P < 0.001). CONCLUSION: Selective killing of HUVECs may be
      achieved by gene transfer of double suicide gene under the regulation of the KDR
      promoter. This finding may provide an optional way to target gene therapy of
      malignant tumors by abrogation of tumor blood vessels.

PMID- 16981264
TI  - Ursodeoxycholic acid improves gastrointestinal motility defects in gallstone
      patients.
AB  - AIM: To simultaneously evaluate the presence of defects in gallbladder and
      gastric emptying, as well as in intestinal transit in gallstone patients (GS) and
      the effect of chronic ursodeoxycholic acid (UDCA) administration on these
      parameters and on serum bile acids and clinical outcome in GS and controls (CTR).
      METHODS: After a standard liquid test meal, gallbla-dder and gastric emptying (by
      ultrasound), oroileal transit time (OITT) (by an immunoenzymatic technique) and
      serum bile acids (by HPLC) were evaluated before and after 3 mo of UDCA (12 mg/kg
      bw/d) or placebo administration in 10 symptomatic GS and 10 matched healthy CTR.
      RESULTS: OITT was longer in GS than in CTR (P < 0.0001); UDCA significantly
      reduced OITT in GS (P < 0.0001), but not in CTR. GS had longer gastric half
      emptying time (t(1/2)) than CTR (P < 0.0044) at baseline; after UDCA, t(1/2)
      significantly decreased (P < 0.006) in GS but not in CTR. Placebo administration
      had no effect on gastric emptying and intestinal transit in both GS and CTR.
      CONCLUSION: The gallstone patient has simultaneous multiple impairments of
      gallbladder and gastric emptying, as well as of intestinal transit. UDCA
      administration restores these defects in GS, without any effect in CTR. These
      results confirm the pathogenetic role of gastrointestinal motility in gallstone
      disease and suggest an additional mechanism of action for UDCA in reducing bile
      cholesterol supersaturation.

PMID- 16981265
TI  - Alteration of peripheral blood lymphocyte subsets in acute pancreatitis.
AB  - AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute
      pancreatitis (AP). METHODS: Twenty patients with mild AP (M-AP) and 15 with
      severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were
      examined at d 1-3, 5, 10 and 30 by means of flow cytometry. RESULTS: A
      significant depletion of circulating lymphocytes was found in AP. In the early
      AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late
      course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d
      10, strong shift in the CD7+/CD19+ ratio implicating predominance of T- over B
      lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of
      the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the
      normal range. Lymphocytes were found to strongly express activation markers:
      CD69, CD25, CD28, CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5, IL-10,
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels
      were significantly increased in both forms of AP. The magnitude of elevation of
      cytokines known to be produced by Th2 was much higher than cytokines produced by
      Th1 cells. CONCLUSION: AP in humans is characterized by significant reduction of
      peripheral blood T- and B-lymphocytes.

PMID- 16981266
TI  - Association of rare SPINK1 gene mutation with another base substitution in
      chronic pancreatitis patients.
AB  - AIM: To verify and expand the known spectrum of serine protease inhibitor Kazal
      type 1 (SPINK1) gene mutations in chronic pancreatitis. METHODS: DNA extracted
      from 172 chronic pancreatitis patients was assayed for SPINK1 gene mutations by
      PCR and DNA sequencing. A control cohort of 90 unrelated healthy individuals was
      analysed by the same methods for presence of common populational polymorphisms,
      and frequency of five-loci haplotypes was calculated. Linkages of gene
      aberrations in single SPINK1 gene copies were analysed by long-distance PCR
      followed by allele-specific PCR and DNA sequencing. RESULTS: The most frequent
      SPINK1 gene mutation N34S was found at a frequency of 6%. Furthermore, we
      detected the heterozygous intervening sequence (IVS) 3 + 2 T > C mutated gene in
      2 German patients and 1 Macedonian chronic pancreatitis patient. In all three
      SPINK1 gene copies an additional rare base substitution was found: 5'untranslated
      region (UTR)-215 G > A. Polymorphism analysis revealed that all three affected
      genes carried the same five-loci haplotype. DNA sequencing of another chronic
      pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any
      mutations in these 3 patients. CONCLUSION: We found in 3 (2%) of 172 chronic
      pancreatitis patients an IVS3 + 2 T > C SPINK1 gene mutation and a base
      substitution 5'UTR-215 G > A in the same gene copy. Most probably the 5'UTR-215 G
      > A represents a rare polymorphism and not a mutation as previously concluded.
      Haplotype analysis suggests a common origin of the IVS3 + 2 T > C mutation in
      these patients.

PMID- 16981267
TI  - Autopsy study of anatomical features of the posterior gastric artery for surgical
      contribution.
AB  - AIM: To investigate features of the posterior gastric artery (PGA) with respect
      to incidence, location and size by using autopsy subjects. METHODS: Autopsies
      were performed on 72 cadavers of adults with no history of abdominal operations.
      The localization of the PGA, the distance between the root of the splenic artery
      and the origin of the PGA, and the external diameter of the PGA were examined.
      RESULTS: The PGA was recognized in all patients. In 70 (97.2%) cadavers, the PGA
      branched from the splenic artery, and one female in this group had two PGAs. In 1
      (1.4%) patient, the PGA originated from the root of the celiac trunk and in
      another (1.4%) patient, the PGA branched from the superior polar artery. Overall,
      the PGA extended for a length of 5.8-12.2 (mean, 8.4) cm from the root of the
      splenic artery, and the external diameter of the PGA was 1.2-3.2 (mean, 2) mm.
      CONCLUSION: The anatomical features of the PGA can be readily observed and
      characterized by autopsy. This study has provided valuable information on the
      features of the PGA useful in the planning of surgical treatment.

PMID- 16981268
TI  - Synchronous occurrence of gastrointestinal stromal tumors and other primary
      gastrointestinal neoplasms.
AB  - AIM: To review clinical and pathologic features of Gastrointestinal stromal
      tumors (GISTs) occurring synchronously with other primary gastrointestinal
      neoplasms. METHODS: Twenty-eight patients with primary GIST were treated at our
      institution between 1989 and 2005. Clinical and pathologic records were reviewed.
      RESULTS: The gastrointestinal stromal tumor occurred simultaneously with other
      primary GI malignancies in 14% of all patients with GIST. The synchronous stromal
      tumors were located in the stomach and were incidentally found during the
      operation. The coexistent neoplasms were colon adenocarcinoma, gastric cancer (2
      cases) and gastric lymphoma. CONCLUSION: The synchronous occurrence of GISTs and
      other gastrointestinal malignancies is more common than it has been considered.
      The development of gastrointestinal stromal tumors and other neoplasms may
      involve the same carcinogenic agents.

PMID- 16981269
TI  - In vitro and in vivo effects of ferulic acid on gastrointestinal motility:
      inhibition of cisplatin-induced delay in gastric emptying in rats.
AB  - AIM: To study the effects of ferulic acid on gastrointestinal motility both in
      vitro and in vivo. METHODS: Ferulic acid induced concentration-dependent
      stimulation of the basal tone of isolated guinea pig ileum (2-20 micromol/L) and
      isolated rat fundus (0.05-0.4 mmol/L). RESULTS: Ferulic acid significantly
      accelerated the gastrointestinal transit and gastric emptying in rats in a dose
      dependent manner (50-200 mg/kg, po). Cisplatin (2.5-20 mg/kg, ip) induced a dose
      dependent delay in gastric emptying in rats. Pretreatment with ferulic acid dose
      dependently, significantly reversed the cisplatin-induced delay in gastric
      emptying. CONCLUSION: The endogenous prostaglandins (PGs) are involved in
      mediating the stimulant effects of ferulic acid. This effect of dietary ferulic
      acid may help improve other accompanying gastrointestinal symptoms such as
      abdominal discomfort and also may protect against emesis induced by cytotoxic
      drugs.

PMID- 16981270
TI  - Differential reactivity of mouse monoclonal anti-HBs antibodies with recombinant
      mutant HBs antigens.
AB  - AIM: To investigate the reactivity of a panel of 8 mouse anti-hepatitis B surface
      antigen (HBsAg) monoclonal antibodies (mAbs) using a collection of 9 recombinant
      HBsAg mutants with a variety of amino acid substitutions mostly located within
      the "a" region. METHODS: The entire HBs genes previously cloned into a mammalian
      expression vector were transiently transfected into COS7 cells. Two standard
      unmutated sequences of the ayw and adw subtypes served as controls. Secreted
      mutant proteins were collected and measured by three commercial diagnostic
      immunoassays to assess transfection efficiency. Reactivity of anti-HBs mAbs with
      mutated HBsAgs was determined by sandwich enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Reactivity of anti-HBs mAbs with mutated HBsAgs revealed
      different patterns. While three mutants reacted strongly with all mAbs, two
      mutants reacted weakly with only two mAbs and the remaining proteins displayed
      variable degrees of reactivity towards different mAbs. Accordingly, four groups
      of mAbs with different but overlapping reactivity patterns could be envisaged.
      One group consisting of two mAbs (37C5-S7 and 35C6-S11) was found to recognize
      stable linear epitopes conserved in all mutants. Mutations outside the "a"
      determinant at positions 120 (P-->S), 123(T-->N) and 161 (M-->T) were found to
      affect reactivity of these mAbs. CONCLUSION: Our findings could have important
      implications for biophysical studies, vaccination strategies and immunotherapy of
      hepatitis B virus (HBV) mutants.

PMID- 16981271
TI  - Detection of H. pylori infection by ELISA and Western blot techniques and
      evaluation of anti CagA seropositivity in adult Turkish dyspeptic patients.
AB  - AIM: To detect H pylori infection and to evaluate the anti CagA seropositivity in
      adult Turkish dyspeptic patients. METHODS: We evaluated anti-H pylori IgA, IgG
      and anti-CagA antibodies using commercial enzyme-linked immunoassay (ELISA) and
      Western blot in dyspeptic Turkish patients. H pylori status was determined by
      histology and rapid urease testing. RESULTS: Fifty-six patients were entered.
      Forty-eight (85.7%) out of the 56 patients were positive for H pylori. H pylori
      IgG seropositivity was 82.1%, IgA seropositivity 48.2%. CagA ELISA showed that
      IgG was positive in 50% and IgA in 30.4% of those with H pylori infections.
      Western blot showed that IgG seropositivity was 80.4% and IgA seropositivity
      33.9%. Western blot detected IgG antibodies with reactivity to CagA in 50%, VacA
      in 62.5%, UreB in 87.5%, UreA in 80.4%, and OMP in 57.1%. None of the tests had a
      sensitivity and specificity above 80%. CONCLUSION: None of these commercial tests
      seems clinically useful for H pylori detection in adult dyspeptic patients, while
      Western blot can give seropositivity and determine anti-CagA, VacA virulence
      factor status of Turkish dyspeptic patients in the Izmir region.

PMID- 16981272
TI  - Dose-related effects of dexamethasone on liver damage due to bile duct ligation
      in rats.
AB  - AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile
      duct ligation. METHODS: A total of 40 male Sprague-Dawley rats, weighing 165-205
      g, were used in this study. Group 1 (sham-control, n = 10) rats underwent
      laparotomy alone and the bile duct was just dissected from the surrounding
      tissue. Group 2 rats (untreated, n = 10) were subjected to bile duct ligation
      (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10) received a
      daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats
      (high-dose dexa, n = 10) received a daily dose of dexamethasone by orogastric
      tube for 14 d after BDL. At the end of the two-week period, biochemical and
      histological evaluations were processed. RESULTS: The mean serum bilirubin and
      liver enzyme levels significantly decreased, and superoxide dismutase (SOD),
      catalase (CAT) and glutathione peroxidase (GSH-Px) values were significantly
      increased in low-dose dexa and high-dose dexa groups when compared to the
      untreated group. The histopathological score was significantly less in the low
      dose and high-dose dexa groups compared to the untreated rats. In the low-dose
      dexa group, moderate liver damage was seen, while mild liver damage was observed
      in the high-dose dexa group. CONCLUSION: Corticosteroids reduced liver damage
      produced by bile duct obstruction. However, the histopathological score was not
      significantly lower in the high-dose corticosteroid group as compared to the low
      dose group. Thus, low-dose corticosteroid provides a significant reduction of
      liver damage without increased side effects, while high dose is associated not
      with lower fibrosis but with increased side effects.

PMID- 16981273
TI  - Factors associated with H. pylori epidemiology in symptomatic children in Buenos
      Aires, Argentina.
AB  - AIM: To determine prevalence of H pylori infection in symptomatic children in
      Buenos Aires, Argentina, and to investigate factors associated with H pylori
      positivity. METHODS: A total of 395 children with upper gastrointestinal symptoms
      referred to the Gastroenterology Unit of the Children Hospital "Sor Maria
      Ludovica" were evaluated for the presence of H pylori by the (13)C-Urea Breath
      Test ((13)C-UBT). A questionnaire was applied to the recruited population.
      RESULTS: Prevalence of H pylori infection was 40.0% in this population (mean age
      9.97 +/- 3.1 years). The factors associated with H pylori positivity were number
      of siblings (P < 0.001), presence of pet cats (P = 0.03) and birds (P = 0.04) in
      the household, and antecedents of gastritis among family members (P = 0.01).
      After multivariate analysis, number of siblings [Odds ratio (OR) = 1.39; 95% CI,
      1.20-1.61] and contact with pet cats (OR = 1.76; 95% CI, 1.00-3.09) remained as
      variables associated with H pylori infection. CONCLUSION: The prevalence of H
      pylori infection in children with upper gastrointestinal symptoms in Argentina
      was similar to that reported in developed countries. Children from families with
      a higher crowding index and presence of pet cats have a higher risk of being
      colonized with H pylori.

PMID- 16981274
TI  - Treatment of gastric precancerous lesions with Weiansan.
AB  - AIM: To observe the curative effect of Weiansan (WAS) on gastric precancerous
      lesions (GPL) and H pylori elimination. METHODS: Seventy-six patients with GPL
      were randomly divided into two groups: WAS group (n = 42) and Weifuchun (WFC)
      group (n = 34). The patients in the WAS group were administered 5 g WAS 3 times a
      day, and the patients in the WFC group took WFC (4 tablets) 3 times a day. To
      monitor inflammation of gastric mucosa, degree of glandular atrophy (GA),
      intestinal metaplasia (IM) and dysplasia, and H pylori infection, all patients
      underwent gastroscopy and biopsy with pathological examination before and after
      treatment. Fifty male Sprague-Dawley (SD) rats were used in animal experiments.
      Of these, 10 served as the control group (n = 10), 40 were given ranitidine
      combined with N-methyl-N(1)-nitro-N-nitrosoguanidine (MNNG) for 12 wk and divided
      into 4 groups randomly: model group (n = 10), high-dose WAS group (n = 10), low
      dose WAS group (n = 10) and WFC group (n = 10). Twelve weeks later, all rats were
      killed and a 2 cm multiply 1 cm tissue was taken from the lesser curvature of the
      gastric antrum. H pylori infection was determined by the fast urease method.
      RESULTS: The curative effect in WAS groups was similar to that in WFC groups.
      There was no statistical difference in degree of GA, IM and dysplasia between WAS
      and WFC groups. The rate of H pylori infection in the model group
      (positive/negative: 9/1) was significantly higher than that in the control group
      (positive/negative: 1/9) (P < 0.01). H pylori elimination in the high-dose WAS
      group (positive/negative: 4/6) and low-dose WAS group (positive/negative: 6/4)
      was similar to that in the WFC group (positive/negative: 4/6) (P > 0.05).
      CONCLUSION: WAS improves clinical symptoms by suppressing GA, IM and dysplasia
      and eliminating H pylori.

PMID- 16981275
TI  - Colonic metastasis of Klatskin tumor: case report and discussion of the current
      literature.
AB  - We report the case of a 65-year old male patient who initially presented with
      recurrent episodes of upper abdominal pain, lack of appetite and weight loss.
      Abdominal ultrasound indicated enlarged intrahepatic bile ducts, abdominal CT
      scan and ERC were performed and bile duct carcinoma (Klatskin Type III b) was
      diagnosed. The tumor was located in the segments 2, 3, 4 and 1 with possible
      invasion of the left intrahepatic portal vein. Both the segments 2 and 3 of the
      liver were atrophic and displayed a cholestatic bile duct system. Preoperatively
      an intraductal stent was placed in the left bile duct using ERC to drain the left
      hepatic lobe. A specimen of the ascites present preoperatively displayed no
      malignant cells. After evaluation of the preoperatively obtained data left
      hepatic resection was planned. Following laparotomy we found local peritoneal
      carcinosis in the ligamentum hepatoduodenale with lymphatic nodules that tested
      positive for cholangiocellular carcinoma in online pathological examination. In
      the course of further exploration of the abdomen a solid tumor was detected in
      the sigmoid colon. Regarding the advanced stage of the neoplasm it was decided to
      cancel hemihepatectomy and perform sigmoid resection only in order to guarantee
      uncomplicated intestinal passage. The sigmoid colon was removed by a typical
      resection technique with end-to-end anastomosis. Histological examination of the
      resected sigmoid revealed transmural manifestation of a malignant neoplastic
      process with both a tubular and a solid growth pattern in conformity with
      metastasis of a Klatskin tumor. The mucosal layer showed no neoplastic
      alteration. Peritoneal carcinosis is a common phenomenon in the dissemination
      pattern of advanced-stage Klatskin tumors, yet to our knowledge this is the first
      case of intramural colonic growth following peritoneal metastasis.

PMID- 16981276
TI  - Multiplex neuritis in a patient with autoimmune hepatitis: a case report.
AB  - A 37-year old woman presented with a 9-year history of hepatitis of unknown
      origin and aminotransferases within a 3-fold upper limit of normal. Autoimmune
      hepatitis (AIH) was diagnosed on the basis of elevated aminotransferases, soluble
      liver antigen/liver pancreas (SLA/LP) autoantibodies and characteristic
      histology. Immunosuppressive therapy led to rapid normalization of
      aminotransferases. Two years later, the patient developed left sided hemisensory
      deficits under maintenance therapy of prednisolone and azathioprine (AZT). Later
      she developed right foot drop and paraesthesia in the ulnar innervation territory
      on both sides. Magnetic resonance imaging (MRI) and cerebral panangiography
      suggested cerebral vasculitis. Neurological investigation and electromyography
      disclosed multiplex neuritis (MN) probably due to vasculitis. Consistent with
      this diagnosis, autoantibodies to extractable nuclear antigens were detectable in
      serum. Immunosuppression was changed to oral 150 mg cyclophosphamide (CPM0) per
      day. Prednisolone was increased to 40 mg/d and then gradually tapered to 5 mg.
      Oral CPM was administered up to a total dose of 40 g and then substituted by 6
      times of an intervall infusion therapy of CPM (600 mg/m(2)). Almost complete
      motoric remission was achieved after 3 mo of CPM. Sensibility remained reduced in
      the right peroneal innervation territory. Follow-up of cranial MRI provided
      stable findings without any new or progressive lesions. This is the first report
      of multiplex neuritis in a patient with autoimmune hepatitis.

PMID- 16981277
TI  - A left-sided periappendiceal abscess in an adult with intestinal malrotation.
AB  - Left-sided periappendiceal abscesses occur in association with two types of
      congenital anomaly: intestinal malrotation and situs inversus. It is difficult to
      obtain an accurate preoperative diagnosis of these abscesses due to the abnormal
      position of the appendix. We present an unusual case of a left-sided
      periappendiceal abscess in an adult with intestinal malrotation, the diagnosis of
      which was a challenge.

PMID- 16981278
TI  - Stump appendicitis is a rare delayed complication of appendectomy: A case report.
AB  - Stump appendicitis is an acute inflammation of the residual appendix and one of
      the rare complications after appendectomy. Paying attention to the possibility of
      stump appendicitis in patients with right lower abdominal pain after appendectomy
      can prevent the delay of diagnosis and treatment. In patients with stump
      appendicitis, CT scan not only assists in making an accurate preoperative
      diagnosis but also excludes other etiologies. We report a 47-year old man with
      preoperatively diagnosed stump appendicitis by CT, who underwent an open
      appendectomy 20 years ago.

PMID- 16981279
TI  - Ruptured high flow gastric varices with an intratumoral arterioportal shunt
      treated with balloon-occluded retrograde transvenous obliteration during
      temporary balloon occlusion of a hepatic artery.
AB  - A patient presented with hematemesis due to gastric variceal bleeding with an
      intratumoral arterioportal shunt. Contrast-enhanced CT revealed gastric varices
      and hepatocellular carcinoma with tumor thrombi in the right portal vein.
      Angiography and angio-CT revealed a marked intratumoral arterioportal shunt
      accompanied with reflux into the main portal vein and gastric varices. Balloon
      occluded retrograde venography from the gastro-renal shunt showed no
      visualization of gastric varices due to rapid blood flow through the intratumoral
      arterioportal shunt. The hepatic artery was temporarily occluded with a balloon
      catheter to reduce the blood flow through the arterioportal shunt, and then
      concurrent balloon-occluded retrograde transvenous obliteration (BRTO) was
      achieved. Vital signs stabilized immediately thereafter, and contrast-enhanced CT
      revealed thrombosed gastric varices. Worsening of hepatic function was not
      recognized. BRTO combined with temporary occlusion of the hepatic artery is a
      feasible interventional procedure for ruptured high flow gastric varices with an
      intratumoral arterioportal shunt.

PMID- 16981281
TI  - An unusual cause of hematemesis: Goiter.
AB  - Downhill varices are located in the upper part of the esophagus and are usually
      related to superior vena cava obstruction. Bleeding from these varices is
      extremely rare. We describe a 77-year-old patient with hematemesis due to
      downhill varices as a result of recurrent goiter. A right lobe thyroidectomy was
      carried out with disappearance of the varices.

PMID- 16981280
TI  - Successful treatment of giant rectal varices by modified percutaneous
      transhepatic obliteration with sclerosant: Report of a case.
AB  - We present a female patient with continuous melena, diagnosed with rectal
      variceal bleeding. She had a history of esophageal varices, which were treated
      with endoscopic therapy. Five years after the treatment of esophageal varices,
      continuous melena occurred. Since colonoscopy showed that the melena was caused
      by giant rectal varices, we thought that they were not suitable to receive
      endoscopic treatment. We chose the modified percutaneous transhepatic
      obliteration with sclerosant, which is one of the interventional radiology
      techniques but a new clinical procedure for rectal varices. After the patient
      received this therapy, her condition of rectal varices was markedly improved.

PMID- 16981282
TI  - Hepatic venous outflow obstruction after piggyback liver transplantation by an
      unusual mechanism: report of a case.
AB  - Hepatic venous outflow obstruction after piggyback liver transplantation is a
      very rare complication. An unusual mechanism aggravating it is reported. A 33
      year-old man with end-stage hepatitis B liver cirrhosis underwent a piggyback
      orthotopic liver transplantation using a full-size cadaveric graft. Two months
      after transplantation, he developed gross ascites refractory to maximal diuretic
      therapy. Doppler ultrasound showed patent portal and hepatic veins. Serial
      computed tomography scans revealed a hypoperfused right posterior segment of the
      liver which subsequently underwent atrophy. Hepatic venography demonstrated a
      high-grade stenosis with an element of torsion of venous drainage at the
      anastomosis. The stenosis was successfully treated with repeated percutaneous
      balloon angioplasty. The patient remained asymptomatic six months afterwards with
      complete resolution of ascites and peripheral edema. We postulate that liver
      allograft segmental hypoperfusion and atrophy may aggravate or result in a
      hepatic venous outflow problem by the mechanism of torsion effect. Percutaneous
      balloon angioplasty is a safe and effective treatment modality for anastomotic
      stenosis.

PMID- 16981283
TI  - Primary squamous cell carcinoma of the liver: a successful surgically treated
      case.
AB  - Primary squamous cell carcinoma (SCC) of the liver is rare. Totally nine such
      cases have been reported in the literature. Primary SCC of the liver has been
      reported to be associated with hepatic teratoma, hepatic cyst, or
      hepatolithiasis. Complete remission of poorly differentiated SCC of the liver
      could be achieved by systemic chemotherapy followed by surgery or remarkably
      respond to hepatic arterial injection of low dose chemotherapeutic drugs. Here we
      report the first case of primary SCC of the liver presenting as a solid tumor and
      receiving successful hepatic resection with 9-mo disease free survival.

PMID- 16981284
TI  - Rare cause of ileus in the mesenteric cavity of terminal ileum: a report of three
      cases.
AB  - Internal herniation is one of the rare reasons of intestine clog, which is hard
      to diagnose and usually needs an urgent surgical treatment. We report 3 patients
      with internal herniation in the mesenteric cavity of the terminal ileum. Besides
      intestinal congestion, they also had peritoneal irritation. Laparotomy revealed
      that herniation caused disorder in nutrition of the intestine and necrosis. The
      patients underwent subtotal small intestine resection and were discharged 10, 12
      and 14 d after operation.

PMID- 16981285
TI  - Microscopic polyangiitis associated with primary biliary cirrhosis: a causal or
      casual association?
AB  - The association between microscopic polyangiitis (MPA) and primary biliary
      cirrhosis (PBC) has seldom been reported. We describe a patient with PBC and MPA
      who presented with polyarthritis and pulmonary nodules followed by pauci-immune
      crescentic glomerulonephritis and liver dysfunction. Detection of p-ANCA,
      antimyeloperoxidase, and antimitochondrial antibodies along with liver and renal
      histopathology allowed a diagnosis of MPA and PBC. We also discuss 2 other cases
      that could be unrecognized associations of both diseases. Further reports are
      necessary to clarify if the coexistence between PBC and MPA is causal or casual.

PMID- 16981286
TI  - Pulmonary veno-occlusive disease and scleroderma associated pulmonary
      hypertension.
AB  - OBJECTIVE: Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary
      hypertension (PH). We describe a series of 4 patients with systemic sclerosis
      (SSc), concomitant PH, and biopsy-proven/presumed PVOD. We review the literature
      describing the association of PVOD and SSc and discuss diagnostic features and
      treatment implications. In our case series, treatment with an endothelin receptor
      antagonist did not confer a beneficial treatment effect.

PMID- 16981287
TI  - Hypertrophic pachymeningitis in rheumatoid arthritis after adalimumab
      administration.
AB  - Tumor necrosis factor-a (TNF-a) inhibition, used in the treatment of rheumatoid
      arthritis (RA), is associated with central nervous system (CNS) events including
      new onset and/or exacerbations of pre-existing demyelinating neurological
      diseases. We describe a patient with refractory RA where adalimumab, a fully
      humanized IgG1 monoclonal antibody against TNF-a, may have contributed to the
      development of meningoencephalitis, with brain biopsy suggestive of hypertrophic
      pachymeningitis, a rare complication of this disease. The patient had recurrence
      of neurological symptoms upon repeated administration of adalimumab, and
      resolution of symptoms after withdrawal.

PMID- 16981288
TI  - Anakinra prevents symptoms of familial cold autoinflammatory syndrome and
      Raynaud's disease.
AB  - OBJECTIVE: Familial cold autoinflammatory syndrome (FCAS) is a rare, hereditary
      disorder characterized by cold-induced inflammation. We describe the successful
      longterm treatment of a patient with FCAS with anakinra, an interleukin 1
      receptor antagonist (IL-1Ra). The remarkable response of FCAS and associated
      Raynaud's disease in this patient suggests that IL-1 is an important mediator of
      these inflammatory diseases. Our report supports increasing evidence that
      anakinra plays an important role in the treatment of select chronic inflammatory
      diseases.

PMID- 16981289
TI  - Magnetic resonance imaging identifies features in clinically unaffected knees
      predicting extension of arthritis in children with monoarthritis.
AB  - OBJECTIVE: A proportion of children with oligoarthritis have an aggressive
      disease course. Identifying these children at presentation would help guide
      prognosis and management. We examined if magnetic resonance imaging (MRI) of
      clinically unaffected joints is more sensitive than clinical assessment in
      identifying those at risk of developing arthritis in more than one joint.
      METHODS: Ten children were recruited; they had a mean age of 9.4 (range 5.2-14.2)
      years at presentation of a monoarthritis. MRI of a clinically unaffected knee was
      performed within 4 months of presentation, and was reported by 2 pediatric
      radiologists blinded to the clinical findings. All MR examinations included post
      gadolinium sequences. Joints with clinically apparent arthritis were recorded
      regularly over a median of 37.0 (range 6.6-47.0) months by a median of 6.0 (range
      2-8) pediatric rheumatologists blinded to the MR result. RESULTS: Four children
      developed arthritis in other joints over a median of 3.9 (range 3-6) months after
      the MRI scan; all had abnormal MRI scans at presentation. Three of these
      developed clinical features in the previously normal knee 4-11 months after MRI
      identified small joint effusions, synovial hypertrophy, and lymph node
      enhancement. One child developed a polyarthritis, but never developed clinical
      features in the imaged knee over 3.8 years of followup. Four other children had a
      persistent monoarthropathy with a median followup of 29.5 (range 6.6-42.0)
      months. All 4 had normal MRI. Two children had reactive arthritis. CONCLUSION:
      MRI distinguished between patients with a persistent monoarthritis and those who
      developed further clinical arthritis up to 1 year later. The results suggest a
      widespread inflammatory process may exist in children whose arthritis extends,
      and this has implications for our understanding of disease and the design and
      timing of therapeutic interventions.

PMID- 16981290
TI  - Benefit of intraarticular corticosteroid injection under fluoroscopic guidance
      for subtalar arthritis in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To determine the demographics of subtalar arthritis, the response to
      intraarticular corticosteroid injection, and the injection complication rate in a
      clinic sample of children with juvenile idiopathic arthritis (JIA). METHODS: A
      chart review was performed of all patients at a tertiary medical center who
      underwent subtalar corticosteroid injection during the past 5 years. Injection of
      1 ml of triamcinolone hexacetonide or acetonide into the midsubtalar joint was
      performed using a lateral oblique approach under fluoroscopic guidance.
      Improvement was defined by enhanced foot inversion and eversion at the following
      office visit. RESULTS: Thirty-eight patients underwent 55 subtalar injections
      during the study period. All 7 JIA subtypes were represented. Thirty-one patients
      (82%) had subtalar arthritis at time of JIA diagnosis and 32 (84%) had
      concomitant tibiotalar ankle arthritis. Improvement was observed following 34
      (89%) of the initial 38 injections. The mean duration of improvement was 1.2
      years (SD +/- 0.9). Twenty patients (53%) developed hypopigmentation or
      subcutaneous atrophy. This complication was associated with a higher volume of
      injected corticosteroid per patient weight (p = 0.02) and with less efficacious
      injections (p = 0.04). CONCLUSION: Subtalar arthritis in children with JIA is
      common. Similar to other joints, subtalar arthritis responds to corticosteroid
      injection in approximately 90% of cases and often remains improved for greater
      than one year. Hypopigmentation and subcutaneous atrophy are frequent
      complications and are likely related to the dose of injected corticosteroid and
      possibly the accuracy of needle placement.

PMID- 16981291
TI  - FK506 inhibits murine AA amyloidosis: possible involvement of T cells in
      amyloidogenesis.
AB  - OBJECTIVE: To determine the possibility that T cells represent a potential target
      for therapy in AA amyloidosis. METHODS: AA amyloidosis was induced in C3H/HeN
      mice by concomitant administration of AgNO3 and amyloid-enhancing factor (AEF).
      Mice injected with AgNO3 and AEF received intraperitoneal injections of FK506 (2
      200 microg/day). The degree of splenic amyloid deposition was determined by Congo
      red staining. Serum amyloid A (SAA), interleukin 1beta (IL-1beta), IL-6, and
      tumor necrosis factor-a concentrations were measured by ELISA. AA amyloidosis was
      also induced in ICR mice by injection of Freund's complete adjuvant (FCA) and
      Mycobacterium butyricum without AEF. ICR mice injected with FCA and M. butyricum
      also received intraperitoneal injections of FK506 (200 microg/day) to eliminate
      the possibility that FK506 action might depend upon AEF activity in the amyloid
      formation. Amyloid deposition was also induced with and without AEF in severe
      combined immunodeficient (SCID) mice and nude mice to clarify the role of T cells
      in the mechanism of amyloid formation in AA amyloidosis. RESULTS: FK506 treatment
      significantly reduced the amount of amyloid deposition and incidence of
      amyloidosis without reducing serum SAA and proinflammatory cytokine levels in the
      murine AA amyloidosis models with and without AEF. SCID mice and nude mice showed
      resistance to development of AA amyloidosis. CONCLUSION: Our findings may provide
      a new therapeutic strategy for amyloidosis. The results suggested that T cells
      may play an important role in the mechanism of amyloid formation in AA
      amyloidosis.

PMID- 16981292
TI  - Musculoskeletal findings and disability in alkaptonuria.
AB  - OBJECTIVE: To describe the musculoskeletal (MSK) findings in patients with
      alkaptonuria and to show which of these factors are associated with disability in
      this population. METHODS: This is a prospective cross-sectional MSK assessment of
      subjects. Participants included 53 patients with alkaptonuria across the life
      span, 22 female and 31 male, mean age 43.6 years (10-80 yrs), participating in a
      natural history study supported by the National Human Genome Research Institute
      (NHGRI). Assessments included objective measures of the MSK system (range of
      motion, radiographic assessment of joints and spine, etc.) and questionnaires
      including the Human Activity Profile (HAP), Health Assessment Questionnaire
      (HAQ), SF-36 health survey, and the Fatigue Assessment Instrument. RESULTS: There
      were 18 patients with kyphosis, 16 with scoliosis, 16 with marked reduction in
      range of motion of at least one major joint, 15 with joint replacements of major
      joints, 11 with tendon ruptures. A positive Schober's test was highly correlated
      with substantial functional loss and associated with disability as measured by
      the HAP (p < or = 0.0001), HAQ (p < or = 0.0001), and the physical component
      summary (p < or = 0.0001) of the SF-36 health survey. Severity of lumbar spine
      involvement had the greatest correlation with disability measures (p < or =
      0.0001). All objective and subjective physical measures worsened with age.
      CONCLUSION: Disability is common and severe in patients with alkaptonuria and
      correlates well with physical findings. Disability does not correlate with self
      reports of mental competencies. Aging with alkaptonuria is associated with
      progressive disability.

PMID- 16981293
TI  - IL13RA2 gene polymorphisms are associated with systemic sclerosis.
AB  - OBJECTIVE: To investigate the influence of genetic variability on the phenotypic
      expression of systemic sclerosis (SSc), by testing possible associations between
      single nucleotide polymorphisms (SNP) in IL13RA1 and IL13RA2 genes and SSc in a
      Caucasian population. METHODS: As IL13RA1 and IL13RA2 are located on the X
      chromosome and SSc occurs far more frequently in women than in men, only women
      were genotyped. The study group comprised 97 women with SSc, 36 with diffuse
      (dcSSc) and 61 with limited (lcSSc) cutaneous forms of disease, and 109 healthy
      controls. Patients and controls were Caucasian. We investigated 4 SNP in IL13RA1
      and 3 in IL13RA2 by polymerase chain reaction amplifications and enzymatic
      digestion or primer extension reactions and denaturing high-performance liquid
      chromatography. RESULTS: We detected an association between IL13RA2 rs638376 and
      patients with SSc [p = 0.004, odds ratio (OR) = 1.85, confidence interval (CI)
      1.22-2.74, p corr = 0.02], as well as with dcSSc in that subgroup of patients (p
      = 0.01, OR 2.22, 95% CI 1.27-3.89, p corr = 0.05). The IL13RA2 rs638376G allele
      frequency was higher in patients with SSc (51.6%) than in controls (36.4%, p =
      0.003, OR 1.86, 95% CI 1.24-2.79, p corr = 0.015) and in the subgroup with dcSSc
      (57.6%) than in controls (36.4%, p = 0.003, OR 2.37, 95% CI 1.35-4.15, p corr =
      0.015). One other IL13RA2 SNP was only associated with the dcSSc subgroup: the
      IL13RA2 rs5946040G allele was more common in patients with dcSSc (33.8%) than in
      controls (17%, p = 0.004, OR 2.5, 95% CI 1.36-4.60, p corr = 0.02). CONCLUSION:
      Our data suggest that IL13RA2 gene polymorphisms may be involved in
      susceptibility to SSc. Further studies are under way to show that they contribute
      to disease.

PMID- 16981294
TI  - Postpartum management of women at increased risk of thrombosis--results of a
      Canadian pilot survey.
AB  - OBJECTIVE: To determine current practice patterns in the postpartum management of
      women at increased risk of thrombosis. METHODS: Physicians affiliated with the
      University of Toronto departments of Obstetrics and Gynecology, Rheumatology,
      Hematology, and Obstetric Medicine who provide care to pregnant women were mailed
      a questionnaire that presented 6 clinical scenarios involving postpartum
      management of a woman at risk for thrombosis, with (1) recurrent pregnancy loss
      and antiphospholipid antibody syndrome (APS) treated with aspirin (ASA) in the
      pregnancy; (2) 2 pregnancy losses and a low titer antiphospholipid antibody (aPL)
      treated with ASA and low molecular weight (LMW) heparin with placental
      insufficiency; (3) known APS and pregnancy loss treated with LMW heparin and
      delivered by cesarean section; (4) a previous 17 week fetal death and aPL; (5) a
      previous deep vein thrombosis while on oral contraception; and (6) systemic lupus
      erythematosus and secondary APS with a history of a stillbirth. Physicians were
      asked whether they would recommend postpartum coagulation, and if so to choose
      from a list of treatment options. RESULTS: Of the 71 questionnaires mailed, 44
      were returned (62%). Three physicians replied that their practices do not include
      patients similar to those presented in the cases and chose not to respond to the
      clinical scenarios. Percentages of responders recommending treatment in each
      scenario were 29% for Case 1, 49% for Case 2, 63% for Case 3, 41% for Case 4, 51%
      for Case 5, and 58% for Case 6. Recommendation for treatment differed among
      medical specialties, with rheumatologists being less likely to treat in all
      cases. Prophylactic heparin was selected as the treatment of choice most
      frequently by those recommending anticoagulation 70% (84/120). CONCLUSION:
      Postpartum treatment recommendations for women at increased risk of thrombosis
      are variable across different practitioner specializations demonstrating clinical
      equipoise regarding therapy. More definitive research is needed and broader study
      of physicians involved in the care of these patients is planned to more
      accurately describe and understand the decision to treat these patients.

PMID- 16981295
TI  - The effect of menopause on disease activity in systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the effect of menopause on disease activity and course of
      systemic lupus erythematosus (SLE). METHODS: Patients were identified from the
      University of Toronto lupus clinic database. Menopause was diagnosed on the basis
      of 12 months of amenorrhea. A 3 part study was carried out. Part 1 included an
      inception cohort of 190 women with SLE diagnosed in the premenopausal years
      (Group A) and an inception cohort of 55 women with SLE diagnosed in the
      postmenopausal years (Group B), both followed for a minimum of 3 years. Part 2
      included 49 patients followed in the clinic for at least 3 years before and 3
      years after their menopause (Group C). Part 3 included 193 patients followed for
      6 years entirely in the premenopausal period (Group D) and 76 patients followed
      for 6 years entirely in the postmenopausal period (Group E). Disease activity was
      measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the adjusted mean
      SLEDAI-2K (AMS). Damage was assessed by the Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.
      Comparisons were made using t-tests and chi-square and McNemar tests. A
      multivariate linear regression model was used to establish the impact of
      menopausal status on change in disease related features. RESULTS: In the first 3
      years of disease, AMS was higher in Group A than Group B (6.6 +/- 3.8 vs 5.0 +/-
      3.3, p = 0.003). Damage accrual was higher in Group B than in Group A both in the
      first year and at 3 years. For Group C, AMS and the number of flares per 3 year
      interval were lower in the postmenopausal period. SLICC/ACR damage index was
      greater during the 3 years in the postmenopausal period then in the premenopause
      (p = 0.006). SLEDAI-2K was higher among Group D than Group E at the start of the
      study (6.71 vs 4.86, p = 0.04). AMS for the 6 years was higher in the
      premenopausal than postmenopausal women (5.14 vs 3.54, p </= 0.0001), however,
      the magnitude of change in the first and second 3 year periods was not different
      between Group D and E. The 3 year AMS of patients in Groups C, D, and E was
      plotted by age and menopausal status. The slopes of AMS in the pre- and
      postmenopausal periods were identical, indicating that time and not menopausal
      status is associated with the decrease in disease activity. On the other hand,
      SLICC damage index showed a greater damage in postmenopausal women at any of the
      time points of the study. To further delineate the effect of menopausal status on
      changes in disease activity and damage, multiple linear regressions were
      performed including age at diagnosis, disease duration, and SLEDAI-2K at
      presentation as independent variables. No changes in AMS, number of flares, or
      SLICC/ACR damage index score were associated with the menopausal status.
      CONCLUSION: Although premenopausal women with SLE have more disease activity than
      postmenopausal women with SLE, we have shown that there is a constant rate of
      improvement over time, be it in the premenopause, across the menopause, or
      postmenopause. This improvement is not due to change in menopausal status. Thus
      clinicians should not be anticipating the postmenopausal era in a patient's
      course as a period of natural disease improvement.

PMID- 16981297
TI  - Cost effectiveness of rotavirus vaccines and other interventions for diarrhoeal
      diseases: meeting report 2006.

PMID- 16981296
TI  - Cardiovascular disease and risk factors in patients with rheumatoid arthritis,
      psoriatic arthritis, and ankylosing spondylitis.
AB  - OBJECTIVE: To compare the prevalence of cardiovascular diseases and their risk
      factors between patients with rheumatoid arthritis (RA), psoriatic arthritis
      (PsA), and ankylosing spondylitis (AS) and control subjects. METHODS: Data for
      patients continuously enrolled in an integrated outcomes database between January
      1, 2001, and December 31, 2002, with International Classification of Diseases,
      9th Revision codes of 714.x (RA), 696.0 (PsA), or 720.0 (AS) were evaluated in
      this cross-sectional comparative study. Control groups were established for each
      patient group (1:4 ratio) by matching on the basis of age, sex, geographic
      region, and length of time in plan. Age- and sex-adjusted prevalence of
      cardiovascular comorbidities and risk factors were calculated; the prevalence
      ratio of the comorbidities and risk factors for the patient groups compared with
      the control population were estimated. Use of selected cardiovascular medications
      was also compared between patient and control groups. RESULTS: The RA, PsA, and
      AS cohorts comprised 28,208, 3066, and 1843 patients, respectively. The
      prevalence ratio of ischemic heart disease (1.5, 1.3, 1.2), atherosclerosis (1.9,
      1.4, 1.5), peripheral vascular disease (2.4, 1.6, 1.6), congestive heart failure
      (2.0, 1.5, 1.8), cerebrovascular disease (1.6, 1.3, 1.7), type II diabetes (1.4,
      1.5, 1.2), hyperlipidemia (1.2, 1.2, 1.2), and hypertension (1.3, 1.3, 1.3) were
      higher in patients than controls. For RA, PsA, and AS, use of angiotensin
      converting enzyme inhibitors, calcium channel blockers, diuretics,
      nitrates/vasodilators, anticoagulants, and antihyperlipidemia agents was
      significantly higher in patients than controls. CONCLUSION: Cardiovascular
      diseases and their risk factors were more common in patients with RA, PsA, and AS
      than in matched controls.

PMID- 16981298
TI  - Practical ethics. Fore!

PMID- 16981299
TI  - Evidence into practice: the mental health hurdle is high.

PMID- 16981300
TI  - Sipuleucel-T shows partial advantage in prostate cancer.

PMID- 16981301
TI  - Unfunded intravenous drugs recommended.

PMID- 16981302
TI  - Aptamers as potential probes for cancer.

PMID- 16981303
TI  - Erythropoietin helps children with cancer-related anaemia.

PMID- 16981304
TI  - Experts question benefits of tamoxifen.

PMID- 16981305
TI  - Hormones & you. Precocious puberty.

PMID- 16981306
TI  - DVT or not DVT?

PMID- 16981307
TI  - [Epidemiology of risk factors which put hypertense patients at risk of
      cardiovascular disease].

PMID- 16981308
TI  - Shear stress stimulates phosphorylation of protein kinase A substrate proteins
      including endothelial nitric oxide synthase in endothelial cells.

PMID- 16981309
TI  - Beverage ingredients can form carcinogen.

PMID- 16981310
TI  - Influence of rinsing and expectoration after toothbrushing on fluoride dose and
      ingested amount by use of conventional and children's fluoride dentifrices.
AB  - The purpose of this study was to assess the amount of ingested fluoride and the
      fluoride dose to which children are subjected during toothbrushing with a
      conventional dentifrice (1500 ppm F) and a children's dentifrice with special
      flavor (1100 ppm F) and evaluate the influence of rinsing and expectoration after
      brushing. Six brushings followed by 6 residue collections (3 per dentifrice) were
      performed by 42 Brazilian children (aged 20 to 30 months). The concentration of
      fluoride in the residues and dentifrices was determined. The amount ingested was
      obtained by the difference principal. 64.3% of the children did not expectorate
      or rinse after brushing. For both toothpastes, no significant difference was
      found for fluoride doses comparing children that rinsed to those that did not
      rinse (p > or = 0.05). When children's toothpaste was used, children who did not
      expectorate were exposed to a higher dose than those who did expectorate (p =
      0.032). The same was not observed when conventional toothpaste (p = 0.081) was
      used. In conclusion, rinsing and expectoration after brushing had no influence on
      the dose of fluoride to which children were exposed by use of the dentifrices.
      However, expectoration was directly associated to the fluoride dose when the
      children's dentifrice was used.

PMID- 16981312
TI  - New adult concerns on antidepressants.

PMID- 16981311
TI  - Vaccines: more reasons to immunize.

PMID- 16981313
TI  - Association between job strain and nutrient intake by diet in working population:
      the role of shift work.

PMID- 16981314
TI  - Tacrolimus for Crohn's disease.
AB  - (1) Tacrolimus (FK-506) is an immunosuppressant that is being investigated for
      use in patients with Crohn's disease, mainly in those with refractory illness and
      fistulizing patterns of the disease. (2) Evidence from a small, randomized
      controlled trial indicates that, compared with placebo, tacrolimus is associated
      with higher rates of improvement and similar rates of remission in those with
      fistulizing patterns of disease. (3) Nephrotoxicity, which has been reported with
      the use of tacrolimus in clinical trials, seems to improve with dose reduction,
      but may be associated with irreversible histologic changes. (4) More studies are
      needed to determine the optimal dose and duration of therapy, and whether the
      drug is beneficial to patients with non-fistulizing patterns of Crohn's disease.

PMID- 16981315
TI  - Screening programs.

PMID- 16981316
TI  - Bibliography. Current world literature. Kidney cancer.

PMID- 16981317
TI  - Vertebroplasty.

PMID- 16981318
TI  - HIV testing in Scotland. Are we meeting the standard? BASHH Scotland national
      audit 2004.
AB  - Most sexually transmitted infections (STIs) are associated with increased risk of
      HIV transmission. The draft Scottish Sexual Health Strategy (2003) proposed that
      'HIV testing [should be] offered to all GUM clinic attendees not known to be HIV
      infected who present with a new STI. ... Reasons for non-uptake should be
      recorded.' We performed a national audit comparing practice in Scottish
      genitourinary (GU) medicine services against these standards. The results show
      that practice is highly variable but overall in 2004 Scottish GU medicine clinics
      were failing to meet the strategy standard.

PMID- 16981319
TI  - The diagnosis of art: exophthalmos--Gustave Dore's ogre.

PMID- 16981320
TI  - The endocrine pancreas. Functional morphology and histopathology.

PMID- 16981321
TI  - Chemical and biological aspects of insulin and proinsulin.

PMID- 16981322
TI  - Insulin secretion and the development of diabetes mellitus in the adult.

PMID- 16981323
TI  - Application of radioimmunologic methods to problems in insulin antigenicity and
      hormonal assay.

PMID- 16981324
TI  - Insulin preparations and the clinical use of insulin.

PMID- 16981325
TI  - Feasibility of physical training after myocardial infarction and its effect on
      return to work, morbidity and mortality.
AB  - The purpose of this work on patients with myocardial infarction was to find out
      whether physical rehabilitation based on spontaneous home training can be carried
      out in practice, and whether such rehabilitation brings about favourable changes
      in the symptoms, clinical findings and metabolic risk factors. A further
      objective was to find out whether the physical condition of the patients is
      improved, and whether the rehabilitation has any effect on the prognosis and
      return to work. The training group consisted of 180 patients, 143 men and 37
      women. The control group comprised 200 patients, 166 men and 34 women. All the
      patients were of working-age, (under 65 yrs) and all were treated in the Clinic
      of Internal Medicine, University Central Hospital of Oulu. Mobilization was
      early: the intramural infarctions were discharged on the 12th day, and the
      transmural ones on the 16th day. Rehabilitation was started 10 weeks after the
      onset of infarction. The training subjects came for a chalistenic session in
      groups of 5-7, once a month. During the session they learnt a 30-minute series of
      chalistenic movements under the instruction of a physiotherapist, and the
      supervision of a physician. The chalistenic program was an interval type program,
      involving all the large muscle groups and including running on the spot. The
      training became progressively more strenuous every month. The trainers were to
      perform the program every day at home. During each session in a gymnastic hall,
      the subjects took a bicycle ergometer test. The controls came for an ergometric
      test monthly. The patients were examined in an outpatient department every third
      month. The improvement of their physical condition was followed by determining
      the submaximal value of aerobic power, measured as the work load at a heart rate
      of 130 per minute (Physical Working Capacity 130). Furthermore, the subjective
      maximum-of about one fourth of the trainers and controls was determined in the
      ergometric test. The program turned out to be suitable. After 6 months, 78% of
      the training men and 65% of the training women were still participating, and 67%
      of the training men and 62% of the training women attended the last session after
      12 months. The chalistenic home program was carried out enthusiastically. Of the
      training men who were still participating after 6 months, 55% did their exercises
      on 6-7 days of the week, the corresponding figure for the training women being
      70%; after a year 51% of the men and 73% of the women were still equally active.
      At the time of the 12-month checkup, 15% of the men and 14% of the women did an
      insignificant amount of chalistenic exercises (0-2 times a week). Rehabilitation
      had no effect on the clinical condition of the trainers, for no significant
      differences were noted in the symptoms of coronary disease and the clinical
      findings between the training subjects and the controls. One indication of a
      possible favourable training effect was the decrease of prolonged chest pains in
      the male training group, during the follow-up period. The blood pressure of the
      training men and the training women declined, but the difference in comparison
      with the controls was not significant. At the end of the follow-up year the
      training men were less fatigued subjectively than the controls, which may be
      indicative of a favourable psychic effect of rehabilitation. Rehabilitation had
      no effect on the smoking habits. There were no significant differences in the ECG
      findings between the trainers and the controls. The relative heart volume of both
      the training men and the training women increased during the year. In the initial
      checkup, the mean relative heart volume of the training men was 496 cm3/m2 and
      that of the training women 487 cm3/m2, while at the end of the year the figures
      were 506 cm3/m2 for men and 530 cm3/m2 for women. The difference between the
      trainers and the controls was almost significant in both groups at the end of the
      year. The clinical findings in the training group showed no signs of an increase
      of heart failure at the end of the year. Rehabilitation had no effect on serum
      cholesterol, serum triglycerides or serum urate, or 2-hour glucose tolerance. No
      association between training and the increase in physical working capacity 130
      could be shown. PWC 130 increased significantly in the groups of trainers and
      controls, but more so in the control group. At the end of the year, the trainers
      had a 13.3% higher PWC 130 and the controls an 18.3% higher PWC 130 than observed
      initially. PWC 130 improved by over 20% in 39.1% of the trainers and 44.6% of the
      controls. The physical working capacity improved more rapidly in the group of
      trainers than in the control group. Those training men, however, for whom the
      subjective maximum was determined, seemed to improve their physical working
      capacity more than the controls, for the subjective maximum of the training men
      improved significantly (39.3%). The improvement among the control men was not
      significant (31.7%). The training effect achieved by the training men was
      probably peripheral, and did not become manifest in the PWC 130 measurements.
      Rehabilitation had no effect on the return to work. Forty (42.1%) of the training
      men recovered their working capacity, and 37 (39%) of these returned to their
      previous employment; the corresponding figures for the control men were 36 (33%)
      and 35 (32.1%). Seven (25.9%) of the training women and 5 (33.3%) of the control
      women resumed their previous employment. The prognosis of the training subjects
      was followed for an average of 31.5 months and that of the controls for an
      average of 26.5 months. During the follow-up period, 21 trainers (11.7%) and 29
      controls (14.5%) suffered a re-infarction. There were 18 (10%) coronary deaths in
      the training group and 28 (14%) in the control group. During the first year 3.5%
      of the trainers and 8% of the controls died. During the second year mortality was
      3.6% in the training group and 5.5% in the control group. The trainers and
      controls did not differ significantly as regards recidivous infarctions and
      coronary deaths. It should be noted, however, that the differences in both
      recidivous morbidity and coronary mortality were always in the same direction:
      the trainers had lower values of recidivous morbidity and coronary mortality than
      the controls. Training may have had an effect on the prognosis.

PMID- 16981326
TI  - Graft renders dental visits spalike, complete with metaphoric beach dunes, at the
      sun-bright KU64 clinic in Berlin.

PMID- 16981327
TI  - [Study on the epidemiology and etiologic agent of Dengue fever outbreaks in
      Fuzhou in 2004].
AB  - OBJECTIVE: To study the epidemiology and etiologic characteristics of a Dengue
      fever outbreak in Fuzhou from the beginning of September to the end of October in
      2004 in order to understand the source of infection. METHODS: Data on descriptive
      epidemiology was collected to study the characteristics and related factors to
      the epidemic. Dengue virus was isolated through the use of C6/36 cell line while
      viral serotypes were identified by indirect immunofluorecent assay with type
      specific monoclonal antibody. The sources of infection were traced by nucleotide
      sequencing. RESULTS: During the epidemic, 93 cases occured consistently with the
      region entomoplily growth and decay. The viruses of 6 strains isolated from 10
      patients' blood specimens were identified as dengue virus type 1. Phylogenetic
      evidence suggested that the viral isolate had high genetic relation with the
      isolates from Kampuchea (DENV-1/KHM/2001; GenBank Accession No. L0904278).
      CONCLUSION: The epidemic was caused by introduction of patients migrating into
      Fuzhou.

PMID- 16981328
TI  - [Molecular identification and genetic analysis of an echovirus 19-associated
      epidemic of aseptic encephalitis].
AB  - OBJECTIVE: To ascertain the pathogen of aseptic encephalitis epidemic in Long-Yan
      city in Fujian, and to find out the genetic characteristics of the virus.
      METHODS: Rapid detection of enteroviral RNA by reverse transcription
      polymerasechain reaction (RT-PCR) was directly carried out in cerebrospinal
      fluid(CSF) to isolate and identify the viruses from CSF at the same time, and to
      detect the neutralization antibody in two serum specimens collected in acute and
      convalescence phase. Nucleotides of VP1 region was also analyzed by constructing
      phylogenetic tree. RESULTS: ECHO 19 infection was rapidly diagnosed and sequence
      analysed by RT-PCR, and then echovirus type 19 from 16 of 30 CSF samples (53.33%)
      was isolated and detected using RD and Hep-2 cells simultaneity. The titer of
      ECHO 19 neutralization antibody became positive or increased by 4 times from
      acute to convalescence phase in 4 of the 5 patients. Phylogenetic analyses of the
      VP1 genes of these isolates showed that their nucleotides identity were 98.9% 
      100.0% which were different from those ECHO 19 from GeneBank database by 13.0%
      22.4%. CONCLUSION: The etiology of the epidemic of aseptic encephalitis was
      attributed to ECHO 19. The method of molecular identification not only provided
      rapid diagnosis of enterovirus infections, but also information about the genetic
      character of the viruses.

PMID- 16981329
TI  - [Study on the coinfection status of Borrelia burgdorferi sensu lato and spotted
      fever group Rickettsia in ticks from Hunchun, Jilin province].
AB  - OBJECTIVE: To understand the coinfection status of Borrelia burgdorferi sensu
      lato (B.b.s.l) and spotted fever group Rickettsia (SFGR) in Hunchun of Jilin
      province, China. METHODS: Polymerase chain reaction (PCR) was used to detect the
      5S-23S rRNA intergenic spacer of B. b. s. l and ompA of SFGR in ticks was
      collected in Hunchun,Jilin province. The amplification products of positive ticks
      were sequenced, and phylogenetic analysis was conducted by PHYLIP software
      package. RESULTS: The infection rate of B. b. s. l was 36.0% in Ixodes
      persulcatus ticks and the SFGR was discovered in I. persulcatus ticks,with an
      infection rate of 2.0%. The coinfection rate of both agents was 2.0%. In 327
      Dermacentor siltarum ticks, the positive rates of B. b. s. l and SFGR were 30.9%
      and 29.1% respectively. 55 ticks (16.8%) were coinfected with the two pathogens.
      The sequence analysis of B. b. s. l showed that the B. b. s. l in Jilin area,
      which were highly homologous, all belonged to B. garinii genotypes. The sequence
      analysis of SFGR positive products showed that the DNA secquence of the newly
      detected agent (JL-95) was close to the two previously described rickettsiae
      which were detected in I. ricinus from Slovakia (called IRS3 and IRS4).
      Phylogenetic relationships inferred from the comparison of these sequences with
      those of other genus Rickettsiae indicated that JL-95, IRS3 and IRS4 constituted
      a new rickettsial genotype and formed a separate cluster among the spotted fever
      group Rickettsiae. CONCLUSION: Coinfection of B. b. s. l and SFGR existed in
      Hunchun, Jilin province. The sequencing of specific fragment confirmed a new SFGR
      which was different from other rickettsiae known in China.

PMID- 16981330
TI  - [Study on blood biochemical variables of obese children screened by new BMI and
      weight-for-height criterion].
AB  - OBJECTIVE: To evaluate the abnormal state of liver function and plasma lipid
      levels of obese schoolchildren who were screened by weight-for-height criterion
      and new body mass index criterion respectively. METHODS: 280 obese children were
      screened by weight-for-height criterion and 125 obese children were screened by
      body mass index criterion in a routine school check-up program. All of the latter
      subjects was included in the former one. One obese child and 1 non-obese child
      were matched for gender and age. 14 items related to liver functions and plasma
      lipids were measured. RESULTS: Of the abnormal items,7 items in 125 obese
      children screened by new BMI criterion and 5 items in 155 "obese children"
      excluded by BMI criterion, were significantly higher than those children among
      controlled group. The abnormal rates were 10.4%-22.9% in the former and 3.2%
      13.0% in the latter. CONCLUSIONS: The new BMI criterion seemed to be more
      stringent than weight-for-height. Less than a half of the obese children screened
      by weight-for-height were taken on obese children by new BMI criterion. The
      overweight children who were screened by BMI criterion also had abnormal liver
      functions and plasma lipids.

PMID- 16981331
TI  - [An epidemiological survey on the psychological stress status for students in 13
      Chinese colleges].
AB  - OBJECTIVE: To explore the main sources causing stress among Chinese college
      students and its distribution. METHODS: A clustered random sampling method was
      conducted to perform the questionnaire on psychological stress among 2007
      students selected from 13 universities. RESULTS: The main sources of
      psychological stress on college students regarding learning task, college
      environment, job-seeking, interpersonal relationship and emotional disorders.
      49.3% of the population experienced mild level of psychological stress, 8.4%
      belonged to critical groups who experienced higher levels of stress,while 0.3%
      experienced severe level of stress. Sophomores and juniors were under more
      stressful situation than freshmen and senior students, while female students felt
      more stressful on learning and job-seeking than males. Male students felt more
      stressful caused by their families, health status, love affairs, social
      adaptation and frustration than females. Students from countryside were under
      more stress than those coming from urbans. Students from ordinary universities
      felt more stressed than those from famous universities and students from western
      areas were under more stress than those from the coastal areas. CONCLUSION:
      Stress had become a severe problem influencing the mental health development
      among college students. The problem needs to be addressed accordingly.

PMID- 16981332
TI  - [Capacity of monitoring system on birth defects during 1990s in China].
AB  - OBJECTIVE: To understand the status and capacity of monitoring system on birth
      defects in China. METHODS: Data regarding 27 groups of birth defects from 57
      monitoring programs in World Atlas of Birth Defects (2nd Edition) published by
      WHO/ICBDMS/EUROCAT/HGP and descriptive analysis by their ranking and contribution
      were carried out. RESULTS: Both hospital-based (Chinese Birth Defects Monitoring
      Network, CBDMN) and population-based (Birth Defect Surveillance System in Thirty
      Counties of Four Provinces, Beijing) monitoring systems showed the same
      characteristics as below: (1) Not enough groups were monitored, with trisomy
      13/18 and congenital heart disease not reported. (2) Prevalence on those 'easily
      observed' group was high and cleft lip with or without cleft palate in CBDMN
      ranked 5 among 57 programs, with similar situation in polydactyly. (3) While
      prevalence rates of internal system and choromosal anomaly were low, CBDMN ranked
      56 with Beijing the only non-reported city among all the 57 programs. (4)
      Unreasonable relationship was seen with prevalence of cleft lip was 5.76,4.02
      times higher than that of cleft palate in CBDMN and in Beijing program. Which was
      1.58 times of the world's means. Prevalence rates of anencephaly and total
      anotia/microtia rose 10.39% while spina bifida, hydrocephaly, and gastroschisis
      had a 4%-5% increase. The prevalence of hypospadias decreased by 4.13% and Down
      syndrome by 3.02%. CONCLUSION: The capacity of birth defects monitoring, both
      hospital-based and population-based, was poor in the 1990s, in China.

PMID- 16981333
TI  - [Surveillance on pathogens of meningococcal meningitis in Beijing, 2005].
AB  - OBJECTIVE: To study the pathogens of meningococcal meningitis (MM) in Beijing,
      2005. METHODS: Blood and cerebrospinal fluid specimens from MM patients were
      detected by polymerase chain reaction. Bacterial strains were analyzed by pulsed
      field gel electrophoresis and multilocus sequence typing. RESULTS: 7 of the blood
      and 5 of cerebrospinal fluid specimens showed positive results. 105 of the
      Neisseria meningitides strains were isolated from the specimens of patients,
      close contacts and healthy carriers. Serogroup A and C Neisseria meningitides
      strains shared the same patterns of pulsed-fieldgel electrophoresis,
      respectively. The sequence type of serogroup A Neisseria meningitides belonged to
      ST7 while the sequence type of serogroup C Neisseria meningitides belonged to
      ST4821. CONCLUSION: Patients suffered from meningococcal meningitis were caused
      by serogroup A (ST7) and C (ST4821) Neisseria meningitides in Beijing, 2005.

PMID- 16981334
TI  - [A novel method for detection and sero-grouping of Nesseria meningitidis].
AB  - OBJECTIVE: We developed a multiplex polymerase chain reaction (PCR) method for
      detection, identification and sero-grouping strains of N. meningitidis. METHODS:
      The gene of crgA was selected for detection and identification of N. meningitidis
      and the 230 bp of crgA fragments were amplified. The genes of siaD and orf-2 were
      used for sero-grouping. With this technology, N. meningitidis of serogroup
      A,B,C,Y and W135 can be differentiated from the specific fragment 400 bp,450
      bp,250 bp, 120 bp,120 bp. RESULTS: This multiple PCR method seemed to be more
      sensitive than latex agglutination. We used this method to detect 61 isolates of
      N. meningitidis and the 230 bp of crgA fragments were amplified. No positive
      results were obtained from on 4 strains of non-N. meningitidis. It seemed that
      the PCR method which was based on crag, was specific in detecting N.
      meningitidis. The 55 strains of N. meningitidis could be grouped into A,B,C,Y and
      W135 by this multiplex PCR. No gene fragment was synthesized for the other
      serogroups of N. meningitidis. No cross-reaction was observed for other bacterial
      species. 4 samples of meningococcal meningitis patients were detected by the
      multiplex PCR and two of them were positive with 400 bp band,representing
      serogroup A of N. meningitidis but all were negative to culture and latex
      agglutination. 18 samples of Japanese (B) encephalitis patients were also
      detected by multiplex PCR and no positive result was obtained which was
      consistent to the finding from culture and latex agglutination. CONCLUSION: This
      multiplex PCR method showed its potential in clinical diagnosis and
      epidemiological investigation.

PMID- 16981335
TI  - [Preliminary study on the genotyping of Mycobacterium leprae on 50 isolates from
      China].
AB  - OBJECTIVE: To understand the genotypic mapping of Mycobacterium leprae identified
      in China and to compare with those from other countries to select suitable
      alleles for epidemiological investigation in the transmission chain of leprosy.
      METHODS: Various number of tandem repeat(VNTR) in genomic DNA of Mycobacterium
      leprae was used in the present genotyping study. 33 skin biopsies from Wenshan
      prefecture,Yunnan province and 17 from other parts of China were studied. DNA
      extracted from skin biopsies of leprosy patients was subjected to PCR followed by
      agarose gel analysis and DNA sequencing to determine the number of repeats.
      RESULTS: Loci GGT-5,12-5,21-3 and 23-3 were as highly homogenous as 100%; The
      homogeneity of loci AC-8, 18-8, 27-5 and rpoT were 97%, 94%, 97% and 85%
      respectively. Loci GTA-9, AC-9 and 6-7 showed significant allelic diversity in
      isolates and the diversity of GTA-9 in Mycobacterium leprae isolated from China
      was also different from those identified other countries. We had subjected loci
      GTA-9 and the ten loci to phylogenetic tree analysis respectively. CONCLUSION:
      The present study revealed that the genotype of Mycobacterium leprae identified
      from China was close to the strains from the Philippines and India although a few
      loci were somehow differentiate. Locus 12-5 manifested as only 3 copies in China
      whereas 4-5 copies predominating in other countries. 12-5 locus might serve as a
      useful marker to diffrentiate Chinese strains from those in other countries.
      However, further study on the diversity of GTA-9 was needed in China. The
      molecular typing of Mycobacterium leprae from different geographic areas might be
      useful in studying the transmission of leprosy.

PMID- 16981336
TI  - [Analysis on the genetic characteristics of the wide-type measles virus
      circulating in Zhejiang province in 2005].
AB  - OBJECTIVE: To study the genetic characteristics of measles viruses circulating in
      Zhejiang province in 2005. METHODS: 4 groups of measles viruses isolated in
      outbreaks and the H and N gene were amplified by reverse transcription polymerase
      chain reaction (RT-PCR). PCR products were purified, sequenced and data was
      analyzed. RESULTS: All of the 4 measles isolates belonged to genotype H1 which
      had been a main genotype containing all of the isolates in China. The isolates
      shared 99.2% -99.7% identity of amino acid sequence on H and 99.8% identity of
      amino acid sequence on N gene. When comparing to the China vaccine strain
      (Shanghai 191), there were 95.2%-95.5% homogeneties and 95.5% homogeneties on H
      and N gene respectively. CONCLUSION: Data from phylogenic trees of H and N gene
      revealed that the wide-type measles viruses circulating in Zhejiang province in
      2005 all belonged to genotype H1. There were obvious differences on genetic
      characteristics between the isolates and the genotype A (Shanghai 191).

PMID- 16981337
TI  - [Primary investigation on variable but nonculturable-state of enterotoxigenic
      Escherichia coli in vitro].
AB  - OBJECTIVE: 7 variable but nonculturable-state strains of Enterotoxigenic
      Escherichia coli (ETEC) during the routine bacterial subculture were found in our
      lab and their morphology and antigen studied. Biological features, antigens and
      pathogenicity of the revertants were also tested and compared to that of the
      initial strains in order to detect their variations. METHODS: Biological
      variations between the variable but nonculturable-state and the revertant of
      every strain were detected, using the routine gram-staining, reverting the
      isolates in animal intestinal, reverting their pathogenicity, serological
      agglutination, biochemical identifications and antibiotic resistance tests.
      RESULTS: For the 7 variable but nonculturable-state strains of ETEC,other than
      the trains that had changed into sphero vegetale cells, there were no other
      obvious variations found. However, high pathogenicity of these strains still
      remained. CONCLUSION: The presence of variable but nonculturable-state strains
      suggested that the routine method of bacteria storage should be changed and more
      attention should be paid to realize the existence of this kind of bacteria during
      the routine surveillance of the communicable diseases.

PMID- 16981338
TI  - [Study on the genotyping and microevolution of Yersinia pestis in the Qinghai
      Tibet Plateau].
AB  - OBJECTIVE: To study the distribution of genomovars and microevolution of Yersinia
      pestis in the Qinghai-Tibet Plateau. METHODS: Primer pairs targeting the twenty
      two different regions(DFRs) were designed for detecting the presence or deletion
      of each DFR in 297 strains isolated from the Qinghai-Tibet Plateau. RESULTS: 9
      genomovars, i. e. Genomovar 1, 5, 6, 7, 8, 10, 11, new type and Ype-ancestor were
      identified in the Marmota himalayana plague focus of the Qinghai-Tibet Plateau.
      Among these genomovars, genomovar 5,8 and 10 were dominant types. The total rate
      of the three genomovars was 80.6% (204/253) and the genomovars in different
      regions were different. All of 44 strains of Y. pestis in the Microtus fuscus
      plague focus of the Qinghai-Tibet Plateau belonged to genomovar 14. CONCLUSION:
      The distribution of genomovars of Y. pestis in the Qinghai-Tibet plateau had
      remarkable characteristics geographically. Based on the distribution of
      genomovars of Y. pestis, the routes of transmission and microevolution of Y.
      pestis were proposed.

PMID- 16981340
TI  - [DNA repair gene XRCC3 Thr241Met polymorphism and susceptibility to cardia and
      non-cardia gastric cancer: a case-control study].
AB  - OBJECTIVE: To study the association between genetic polymorphisms of XRCC3
      Thr241Met gene and susceptibility to gastric cardia and/non-cardia gastric
      cancer, and to investigate the combined effect between genes and surrounding
      environment. METHODS: A case-control study with respective control group was
      conducted. Genotypes were investigated by PCR-RFLP. Unconditional logistic
      regression models were used to estimate odd ratios (ORs) and their 95% confidence
      intervals(95% CI). RESULTS: The frequency of XRCC3 CC, CT and TT genotypes were
      43.2%, 46.5% and 10.3%, respectively in cardia cancer cases and 53.2%, 40.9% and
      5.8% respectively in non-cardia gastric cancer cases while 59.6%, 35.1%, 5.3%,
      respectively in control group. Variated genotypes (CT and TT) increased the risk
      of cardia cancer after adjusting for potential confounders (OR = 1.76, 95% CI:
      1.07-2.90). On cardia cancer risks, there seemed combined effects between
      variated genotype and high rate of alcohol drinking, low intake of fresh
      vegetables and having chronic gastritis. Combined effects between variated
      genotype and smoking, having chronic gastritis were observed in non-gastric
      cancer group. CONCLUSION: XRCC3 variated genotype was one of the risk factors of
      cardia cancer while different risks of factors might exsit between cardia and non
      cardia gastric cancer.

PMID- 16981339
TI  - [A matched case-control study of papillary thyroid carcinoma].
AB  - OBJECTIVE: In order to explore the risk factors of the papillary thyroid
      carcinoma(PTC), a hospital-based matched case-control study was carried out in
      Shanghai. METHODS: Matched by gender, age (+/- 3 years old) and native place,205
      pairs of cases and controls were recruited and studied. Database was established
      with Epi Info 6.0 software. Univariate and multivariate conditional logistic
      regression analysis were carried out with SPSS 11.5 software. RESULTS: Data from
      multivariate conditional logistic regression analysis showed that often drinking
      tea and having better economic living standard 20 years ago were protective
      factors of PTC, with ORs of 0.456 and 0.221 respectively. Personal history of CT
      examination, familial history of cancer and the mother's age was older than 22
      years when the research subject was delivered, were risk factors of PTC, with ORs
      of 12.935, 7.027 and 3.729 respectively. Results data from multivariate analysis
      on female subjects showed that the history of CT examination, mother's age was
      older than 22 (when the subject was delivered) and the history of gynecological
      disease were the risk factors of PTC,with ORs of 107.453,29.246 and 59.521
      respectively. Taking bean products frequently and having higher standard of
      living 20 years ago were the protective factors of PTC,with ORs of 0.025 and 0.
      144 respectively. CONCLUSION: History of CT examination, familial history of
      cancer and the mother's age(older than 22 when the subject was delivered) were
      the risk factors of PTC. Frequent tea drinking habit and having higher standard
      of living 20 years ago were the protective factors of PTC. History of CT
      examination,mother's age (older than 22 when the subject was delivered) and the
      history of gynecological disease appeared the risk factors of PTC for women.
      Habit on frequent bean products taking and had higher standard of living 20 years
      ago were the protective factors of PTC to women.

PMID- 16981341
TI  - [A case-control study on the association between folate and cervical cancer].
AB  - OBJECTIVE: To evaluate the possible effects of folate on cervical carcinogenesis
      and the interaction of folate and human papillomaviruses 16 (HPV16). METHODS: A
      hospital-based case-control study was conducted. 111 hospitalized cases who were
      pathologically diagnosed of having cervical cancer and 111 controls identified
      with hysteromyoma that frequency-matched to cases on age, birth place and
      residential area. A 60-item food-frequency questionnaire (FFQ) were administered
      to estimate the consumption of dietary folate. HPV16 DNA in exfoliated cervical
      cell and serum folate were detected by special PCR and radioimmunoassay
      respectively. RESULTS: HPV16 infection rate in cases (61.26%) was significantly
      higher than that in controls (28.83%), with adjusted OR of 4.95(95% CI:2.49
      9.83).The levels of dietary folate in cases (5.00 microg/kcal +/- 0.41
      microg/kcal) were significantly lower than that in controls (5.14 microg/kcal +/-
      0.35 microg/kcal), but the adjusted OR showing no statistical significance.
      However, serum folate in cases (1.79 ng/ml +/- 1.42 ng/ml) was significantly
      lower than that in controls(2.59 ng/ml +/- 2.81 ng/ml),and there were
      significantly increasing trend in the risk of cervical cancer with reducing level
      of serum folate (chi-squared trend test of P = 0.000). Meanwhile, low-level of
      serum folate and HPV16-infection showed significant interaction in the
      development of cervical cancer, with likelihood ratio test of G = 5.56, P = 0.02.
      CONCLUSION: Results indicated that low levels of folate might increase the risk
      of cervical cancer, and potential synergistic action might exist between low
      level of serum folate and HPV16 in the development of cervical cancer.

PMID- 16981342
TI  - [Meta-analysis on NRAMP1 gene polymorphisms and tuberculosis susceptibility in
      East-Asia population].
AB  - OBJECTIVE: To provide a quantitative summary in estimating the association
      between polymorphisms of 3 loci in NRAMP1 gene and susceptibility to tuberculosis
      in East-Asia population by means of meta-analysis. METHODS: We searched databases
      (MEDLINE, OVID and CBM disc) from January 1995 to May 2005 using "NRAMP1" or
      "SLC11A1", in combination with "tuberculosis", also performed a manual search of
      citations from relevant original studies and literature. For each study involved,
      information was collected concerning the characteristics of the subjects, such as
      mean age of cases and the size of study. These characteristics were used to
      evaluate the sources of variation. Summary ORs and corresponding 95% CI were
      estimated by fixed effects (Mantel-Haenszel) or random effects (DerSimonian and
      Laird) model. To check for publication bias,a funnel plot, using Egger's linear
      regression method, was constructed. Cumulative meta-analysis was performed to
      evaluate whether the summary OR for studies with the polymorphisms of the 3 loci
      in the NRAMP1 gene was changing along with the accumulation of more data. Chi
      square goodness of fit was used to test deviation from Hardy-Weinberg
      equilibrium. RESULTS: Eight publications, with the number of cases and controls
      of 1067 and 1084 respectively, were identified and all genotype frequencies were
      consistent with Hardy-Weinberg equilibrium. The summary ORs for studies with
      polymorphisms of 3' UTR, D543N and INT4 loci of the NRAMPI gene among the East
      Asia population were 1.68(95% CI: 1.31-2.16, P< 0.001), 1.78(95% CI: 1.38-2.30,
      P< 0.001), 1.56 (95% CI: 0.72- 3.35, P = 0.26), respectively when compared with
      their corresponding common homozygotes. Publication bias was not found in the
      studies with the three loci, except for INT4 locus, by Egger linear regression
      method. The cumulative summary effects ORs were 1.85 (P = 0.02) in 2000, 1.35 (P
      = 0.12) in 2002,1.64 (P= 0.001) in 2003, and 1.68 (P<0.001) in 2004 for 3'UTR
      locus, 1.88 (P = 0.001) in 2000,1.65(P = 0.001) in 2002,1.70(P<0.001) in
      2003,1.76(P<0.001) in 2004, and 1.78(P<0.001) in 2005 for D543N locus, and 0.88(P
      = 0:70) in 2002, 2.50(P = 0.41) in 2003, 1.52(P = 0.42) in 2004 and 1.56(P =
      0.26) in 2005 for INT4 loucs. CONCLUSION: Polymorphisms at 3' UTR and D543N loci
      had statistically significant association between the NRAMP1 variants and
      susceptibility to tuberculosis in the East-Asia descendants, and variant in the
      INT4 locus failed to show statistically significant association in the East-Asia
      population.

PMID- 16981343
TI  - [Cost-effectiveness analysis of emergency endoscopic variceal ligation plus
      octreotide in the treatment of acute esophageal variceal bleeding in cirrhotic
      patients].
AB  - OBJECTIVE: To compare and evaluate the cost and effectiveness of endoscopic
      variceal ligation (EVL) at emergency plus octreotide versus octreotide alone in
      the treatment of acute esophageal variceal bleeding in cirrhotic patients.
      METHODS: Seventy-eight patients with active variceal bleeding under emergency
      endoscope, were assigned to two groups receiving either combined therapy of EVL
      at emergency and octreotide ('EVL' group) or a continuous infusion of octreotide
      alone ('octreotide' group). Both efficacy and cost-effectiveness were observed.
      RESULTS: There were no significant differences between the two groups in
      patients' characteristics, supporting treatment or general treatment. In group
      EVL, there appeared a significantly higher rate in controlling bleeding and lower
      complication rate than that of octreotide group(94.4% vs.78.6%, P = 0.045 and
      19.4% vs. 42.9%, P = 0.027, respectively). Early rebleeding and mortality rate
      were also lower in group EVL, but with no significant differences between them
      (2.9% vs. 7.7%, P = 0.358 and 5.6% vs. 14.3%, P = 0.205, respectively). The
      combined therapy had a significantly shorter time of hemostasis, less
      administration of octreoid, fewer units of blood transfusion and shorter hospital
      stay (P < 0.001). The median costs of the combined therapy and octreotide alone
      were RMB 9046.5 Yuan and 13 743.6 Yuan,respectively (P = 0.045). The cost
      effective ratio of group EVL seemed superior to that of octreoid group.
      CONCLUSION: The therapeutic scheme of emergency EVL plus octreotide was a more
      cost-effective one for controlling acute esophageal variceal bleeding.

PMID- 16981344
TI  - [The application of multifactor dimensionality reduction for detecting gene-gene
      interactions].
AB  - OBJECTIVE: To introduce the application of Multifactor Dimensionality Reduction
      (MDR) method for detecting gene-gene interactions in genetic case-control
      studies. METHODS: A brief overview on basic steps involved in the implementation,
      theoretical details, available software as well as the use and features of the
      MDR method were discussed based on a practical research case. RESULTS: Advantages
      of MDR were compared to the conventional statistical approaches, showing that MDR
      method was a novel, nonparametric, genetic model-free approach that was developed
      specifically for detecting gene-gene interactions. Theoretical and empirical
      studies suggested that MDR was having reasonable power for detecting gene-gene
      interactions. Applications of MDR method had found the evidence of gene-gene
      interactions in several diseases such as sporadic breast cancer, atrial
      fibrillation and essential hypertension. CONCLUSION: MDR method could be used for
      detecting gene-gene interactions in genetic case-control studies as having great
      advantages versus the conventional statistical approaches.

PMID- 16981345
TI  - [On the study of natural history of disease and prognosis of epilepsy in China].

PMID- 16981346
TI  - [A newly discovered the rickettsiosis].

PMID- 16981347
TI  - [Research of Haemophilus influenzae type B in China].

PMID- 16981348
TI  - [Study on the epidemiological difference of four kinds of chronic respiratory
      disease in the urban and rural areas of China].

PMID- 16981349
TI  - My declaration of ... well, dependence.

PMID- 16981350
TI  - Healing war's wounds.

PMID- 16981351
TI  - The new first grade: too much too soon?

PMID- 16981352
TI  - How VA hospitals became the best.

PMID- 16981353
TI  - 'We owe it to society to give the wealth back'. Gates tops annual 100 Most
      Powerful list, spotlighting growing role of philanthropy in fighting healthcare's
      ills.
AB  - Modern Healthcare's fifth annual listing of the 100 Most Powerful People in
      Healthcare spotlights executives, providers and other insiders who have their
      fingers on the pulse of the biggest industry trends, such as electronic health
      records, health savings accounts and rising numbers of uninsured patients. Who's
      the most influential person in healthcare? One hint: It's not the president.

PMID- 16981354
TI  - U.S. News & World retort. JCAHO study questions magazine's ranking system.

PMID- 16981355
TI  - USC takes Tenet to court. Trojans fighting for ownership of hospital.

PMID- 16981356
TI  - Gulf Coast still hurting: study.

PMID- 16981357
TI  - Mississippi Medicaid mess. Officials to probe hospital association payments.

PMID- 16981358
TI  - Nurse admissions slowing.

PMID- 16981359
TI  - Many roads to power. Money is important, but there are other means to industry
      clout.

PMID- 16981360
TI  - How we cut drug errors. At one hospital, IT and changed culture saves lives.

PMID- 16981361
TI  - They have staying power. 23 have been 100 Most Powerful perennials.

PMID- 16981362
TI  - Now entering the outpatient zone. Hospitals invest in 'big box' centers for
      outpatient services to help reap rising revenue in that sector and expand their
      reach.

PMID- 16981363
TI  - Star search. In-town recruiting of top docs is once again in vogue as hospitals
      take advantage of regulations that clearly define what's allowed.

PMID- 16981364
TI  - Trusts risk tribunal payouts over rights of oldest workers.

PMID- 16981366
TI  - Community foundation trusts--market forces or forced markets?

PMID- 16981365
TI  - Government consults ahead of new choice framework.

PMID- 16981367
TI  - On the chief exec scramble.

PMID- 16981368
TI  - What affects same-day discharge rates?

PMID- 16981369
TI  - Workforce. Feel the heat.

PMID- 16981370
TI  - On patient stories.

PMID- 16981371
TI  - HR framework. Still in the frame?

PMID- 16981372
TI  - Embryonic war.

PMID- 16981373
TI  - Why Bush and science may yet meet in the middle. A delicate balance.

PMID- 16981374
TI  - Going beyond massage.

PMID- 16981375
TI  - [MS never sleeps!].

PMID- 16981376
TI  - [How risky are beta-2 mimetics?].

PMID- 16981377
TI  - [Otitis externa: which antibiotics are first choice?].

PMID- 16981378
TI  - [Icterus with unusual origin. Why did the alcoholic become yellow?].

PMID- 16981379
TI  - [A good idea poorly impleted. Guidelines--loved and hated].

PMID- 16981380
TI  - [Obesity 2006].
AB  - Despite the fact that the last decade has seen major advances in our knowledge of
      obesity, the average unsatisfactory successes of lifestyle changes and
      pharmacological treatment strategies clearly show how very far obesity research
      and treatment still has to go. What is most regrettable, however, is the fact
      that, in contrast to the WHO, the German Social Security Code V does not
      recognize obesity as a disease. This means ignoring the approaching flood of
      costs associated with obesity, which will put a great strain our health system.

PMID- 16981381
TI  - [Problems with the implementation of medical guidelines].
AB  - Neither today nor tomorrow will medicine be completely encompassed within
      guidelines. Those who have been concerned with developing guidelines in the past
      years are well aware of the limitations involved. At present, the most important
      task is to review the flood of current guidelines to check their compliance with
      the criteria quoted here, as has already been done for English guidelines in the
      internet. In the future, too, other "paths of knowledge" besides guidelines will
      continue to be taken to improve the quality of medical care in Germany. Quality
      management as a whole offers many as yet unused possibilities for making such
      improvements. Academic research and the teaching of quality management would give
      a new impetus to the spreading of guidelines, and achieve greater acceptance.
      These points are necessary, if we are to produce the evidence for the efficacy of
      quality management.

PMID- 16981382
TI  - [Guideline skating for the family doctor].
AB  - The sheer mass of guidelines sometimes gives the physician more of a headache
      rather than the support in his diagnostic and therapeutic endeavors--which is the
      actual service they are supposed to provide. Indeed, different guidelines exist
      for one and the same disease--it all boils down to the specialty concerned.
      Furthermore, proof of the quality of the individual medical guidelines is often
      lacking. Some doctors also worry that their individual work with the patient is
      degenerating ever more into an automated standardized process.

PMID- 16981383
TI  - [To lower blood pressure without medication].

PMID- 16981384
TI  - [Syncope].
AB  - Syncope may be nothing more than a run of the mill faint, or a precursor of
      sudden cardiac death. In persons with a healthy heart, it usually has an
      autonomic-nervous (vasovagal) genesis; when structural heart disease is present
      it is often rhythmogenic. For diagnostic purposes, the tilt-table is indicated
      when neurocardiogenic syncope is suspected, and an electrophysiological
      investigation or long-term monitoring of cardiac rhythm (implantable loop
      recorder) if rhythmogenic syncope is suspected. Neurocardiogenic syncope is
      treated by providing the patient with relevant information, orthostatic training,
      increased intake of fluids and, where necessary, medication. In the case of the
      prognostically serious rhythmogenic syncope, the underlying rhythm disorders are
      treated in accordance with current recommendations.

PMID- 16981385
TI  - [Do you also lack every time a few hundred Euro?].

PMID- 16981386
TI  - [Only if one wants, has to settle accounts with the patient directly].

PMID- 16981387
TI  - [Contract physicians do not let patients wait long!].

PMID- 16981388
TI  - [Therapy concept with future].

PMID- 16981389
TI  - [Improved blood sugar control plus weight loss].

PMID- 16981390
TI  - [Not all antihypertensive agents protect equally well].

PMID- 16981391
TI  - [When ASS, when anticoagulants?].

PMID- 16981392
TI  - [Plus point -- risk reduction].

PMID- 16981393
TI  - [Kidney protection leads to heart protection, too].

PMID- 16981395
TI  - [It happens every summer again].

PMID- 16981394
TI  - [Suspected depression].

PMID- 16981396
TI  - Peripheral neurons innervating the extrinsic smooth penile musculature of the
      pig: experimental study by retrograde transport and immunohistochemistry.
AB  - Peripheral autonomic and sensitive neurons projecting to the extrinsic smooth
      penile musculature of the pig were studied by means of retrograde tracing and
      single-labelling immunofluorescence methods. The fluorescent retrograde tracer
      Fast Blue was injected into the left retractor penis muscle, that was taken as an
      experimental model of the male genital smooth musculature, of 4 castrated pigs.
      After a 7 day survival time, the ipsilateral paravertebral ganglion S1, the
      caudal mesenteric ganglion and the dorsal root ganglion S2 were collected. In
      these ganglia, the presence and the distribution of immunoreactivities to
      cathecolamine- (Tyrosine Hydroxylase), acetylcholine- (Vesicular Acetylcholine
      Transporter), or nitric oxide-synthesizing (neuronal Nitric Oxide Synthase)
      enzymes and to some biologically active peptides (Calcitonine Gene-Related
      Peptide, Leu-Enkephaline, Neuropeptide Y, Substance P and Vasoactive Intestinal
      Peptide) were studied. In paravertebral ganglion S1, Tyrosine Hydroxylase and
      Neuropeptide Y were the most frequently present substances. Also Leu-Enkephaline
      and neuronal Nitric Oxide were present quite frequently, while there was scarce
      immunoreactivity for the other antisera (in decreasing order Substance P,
      Vasoactive Intestinal Peptide, Vesicular Acetylcholine Transporter, Calcitonine
      Gene-Related Peptide). In caudal mesenteric ganglion, in addition to Tyrosine
      Hydroxylase- and Neuropeptide Y-immunoreactivity, Substance P-, Vesicular
      Acetylcholine Transporter-, Vasoactive Intestinal Peptide-, Leu-Enkephaline-
      immunoreactivity were also frequently present, followed by neuronal Nitric Oxide-
      and Calcitonine Gene-Related Peptide- immunoreactivity. In dorsal root ganglion
      S2, Calcitonine Gene-Related Peptide and neuronal Nitric Oxide resulted to be the
      most frequently present neurotransmitters, followed by Vasoactive Intestinal
      Peptide, Vesicular Acetylcholine Transporter, Leu-Enkephaline, Substance P,
      Tyrosine Hydroxylase and Neuropeptide Y.

PMID- 16981397
TI  - Lectin binding in the ependymal cells of the cephalic portion of the nervous
      system in the chick embryo.
AB  - The content, distribution and changes of the glycoconjugates oligosaccharides in
      the ependymal cells of the cephalic portion of the nervous system, in the chick
      embryo from 5 days of incubation till hatching and in the 3 days old chicken,
      were investigated. For this purpose a battery of six HRP-conjugated lectins were
      used (WGA, SBA, UEA I, LTA, PNA, ConA). Enzyme and chemical treatments were
      performed on some sections prior to staining with HRP-lectins. Our findings
      showed a large amount of all the investigated sugar residues at the apical
      portion of the ependymal cells, for the whole considered period of incubation and
      in the 3 days old chicken. This could indicate that also the immature ependymal
      cells (spongiobasts) begin to play a tipical role of the mature cells. The
      presence of cytoplasmic sopranuclear granules, containing D-glucosamine, D
      galactose-(beta --> 3)-N-acetil-D-galactosamine and sialic acid in the early
      stages of incubation, might represent a secretion by the ependymal cells to
      integrate a not yet fully functioning secretion by the choroid plexuses. At the
      ciglia a large amount of oligosaccharides were detected in the second part of the
      period of incubation and in 3 days old chicken. These oligosaccharides could be
      involved in determining and mantaining the movement of the ciglia to facilitate
      the flow of the CSF.

PMID- 16981398
TI  - A histological study on the prenatal development of the palatal rugae in the
      white rat.
AB  - This study was designed to investigate the prenatal development of the palatal
      rugae in the White Rat and to discuss the possible role played by the developing
      rugae in palatal shelf elevation. Extraction of embryos from twenty pregnant
      female rats was carried out in the 12th, 13th, 14th, 15th and 16th day of
      pregnancy. Four embryos from each age were decapitated and their heads were fixed
      and processed. Serial coronal and sagittal sections were made and stained with
      haematoxylin and eosin and with Mallory's trichrome stains. The results of the
      present study revealed that in the 12th day rat embryo the lateral and medial
      surfaces of the vertical palatine processes were covered with epithelium of
      uniform thickness but there was marked epithelial thickening at the junction
      between the lateral surface of the palatine process and the maxillary process
      with increased condensation in the subjacent mesenchyme. In the 13th day, the
      thickened epithelium was invaginated into the underlying mesenchyme to form a
      well-marked groove. In the 14th day, the anterior set of palatal rugae started to
      appear on the future oral surface of the vertical palatine process as three
      vertically arranged areas of epithelial thickenings. In the 15th day, the
      palatine processes became horizontal and the anterior set of rugae became
      apparent in coronal and sagittal sections. In the 16th day, the anterior set of
      rugae became well developed and their thickened epithelium became invaded by the
      subjacent mesenchyme. The posterior set of rugae started to appear as localized
      epithelial thickenings. It was concluded that the anterior set of rugae is
      developed prior to shelf elevation while the posterior set is developed only
      after palatal shelf elevation. The rugae may act as struts which help in keeping
      the palatine shelves horizontal when they have been elevated.

PMID- 16981399
TI  - Histological characteristics of the deep fascia of the upper limb.
AB  - Post-mortem specimens taken from the antebrachial and brachial fasciae of 20
      upper limbs were studied by histological and immunohistochemical staining in
      order to evaluate collagen fibre bundle arrangement, the presence of elastic
      fibres, and the density of innervation in deep muscular fascia. The study
      demonstrated that the fasciae are formed of numerous layers of undulating
      collagen fibre bundles. In each layer, the bundles are parallel to each other,
      whereas adjacent layers show different orientations. Each layer is separated from
      the adjacent one by a thin layer of adipose tissue, like plywood. Many elastic
      fibres and a variety of both free and encapsulated nerve endings, especially
      Ruffini and Pacini corpuscles, are also present, suggesting a proprioceptive
      capacity of the deep fascia. Thanks to the undulating collagen fibre bundles and
      elastic fibres, the fasciae can adapt to stretching, but this is only possible
      within certain limits, beyond which nerve terminations are activated by
      stretching. This mechanism allows a sort of "gate control" on the normal
      activation of intrafascial receptors. The capacity of the various collagen layers
      to slide over each other may be altered in cases of over-use syndrome, trauma or
      surgery. In such cases, the amortising mechanism of the fascia on the nervous
      terminations is lost, causing incorrect paradoxical activation of nerve receptors
      within the fascia, resulting in the propagation of a nociceptive signal even in
      situations of normal physiological stretch. At the same time, the layered
      collagen fibres allow transmission of tension according to the various lines of
      force. This structure of the muscular fascia guarantees perceptive and
      directional continuity along a particular myokinetic chain, acting like a
      transmission belt between two adjacent joints and also between synergic muscle
      groups.

PMID- 16981400
TI  - Behaviour of nitric oxide synthase isoforms in inflammatory human joint diseases:
      an immunohistochemical study.
AB  - Nitric oxide (NO) is produced by nitric oxide synthases (NOS) expressed in
      various human tissues and, depending on the amount of NO produced in each tissue,
      the physiological function of NO is determined. Since increased inducibile nitric
      oxide synthase (iNOS) expression and NO generation are associated with
      pathogenesis of idiopatic osteoarthritis of synovial tissue and data about
      constitutive nitric oxide isoform (cNOS) in this tissue are scarce, in this study
      we investigated the localization and distribution of nitric oxide isoforms in
      normal, acute and chronic diseased synovium. The immunohistochemical and
      histologic analysis was performed in human synovial tissue obtained from 10
      patients with post-traumatic inflammation, 14 patients with idiopatic
      osteoarthritis and normal synovial specimens were obtained from 7 patients
      undergoing surgery for reconstruction of the anterior cruciate ligament.
      Immunohistochemical data showed iNOS was strongly expressed in the synovial
      lining layer, subsynovium and blood vessels from patients with acute and chronic
      inflammation pathology, on the contrary, normal joints were negative. A similar
      pattern of cNOS immunoreactivity was seen in synovial lining and vascular smooth
      muscle in the pathological samples, while in the normal joint the intensity of
      staining was weaker than the inflammed. These data indicate that NO is produced
      locally in the pathological synovial lining not only by iNOS but also by cNOS.

PMID- 16981401
TI  - Urinary nicotine and its metabolites as a biomarker of exposure to environmental
      tobacco smoke.
AB  - The validity of urinary nicotine and its metabolites as a biomarker of exposure
      to environmental tobacco smoke (ETS) has been investigated. After exposure to
      ETS, urine samples were collected from 10 subjects for the analyses of nicotine,
      cotinine and 3'-hydroxycotinine. The former two chemicals were detected in the
      urine of all subjects, and 3'-hydroxycotinine was detected in the urine of 9
      subjects out of 10, indicating these three chemicals can be used as a biomarker
      of ETS exposure. 3'-Hydroxycotinine was not detected in the urine of one subject,
      suggesting that this subject may be a poor metabolizer of nicotine. In 9 subjects
      with 3'-hydroxycotinine excreted, the amounts of nicotine and cotinine started to
      increase after exposure, reached the peak at the end of the second exposure and
      decreased gradually. 3'-Hydroxycotinine started to be excreted into urine from 3
      hours after exposure and kept the same level until 72 hours after exposure. In
      the urine of 72 hours after exposure, the amount of 3'-hydroxycotinine was the
      highest among these three chemicals.

PMID- 16981402
TI  - A retrospective cohort study among iron-steel workers in Anshan, China: exposure
      assessment.
AB  - Although adequate assessment of exposure is needed in epidemiological studies
      among foundry workers, previous studies are often lacking in this aspect. We
      conducted a retrospective cohort study of a Chinese iron and steel company with a
      14-yr follow up during 1980-1993. Exposure assessment was performed for a single
      job, i.e., the current job for the active worker and the longest job for the
      retired or deceased worker as of the end of the follow-up, which was allocated as
      the surrogate of lifetime job and was applied to a job-exposure matrix. Of the
      147,062 cohort members, 52,394 males (43%) and 5,291 females (21%) were exposed
      to any of 15 hazardous factors such as dust, silica, PAHs (polycyclic aromatic
      hydrocarbons), CO (carbon monoxide) and heat. In 2,104 randomly selected samples,
      the exposure assessment of exposed workers based on a single job was found to be
      12-14% lower than the real situation. This study suggests that the exposure
      assessment is valuable in evaluating the health effects among the foundry
      workers, despite some limitations such as underestimation of exposure assessment
      and the lack of data regarding smoking and drinking habits.

PMID- 16981403
TI  - Cyclooxygenase system contributes to the maintenance of post convulsive period of
      epileptic phenomena in the genetically epileptic El mice.
AB  - Recent studies have shown that cytokines and cyclooxygenase (COX)-2 are up
      regulated in the brain of human epilepsy patients and animal models of epilepsy.
      We investigated the effect of inflammatory responses induced by intramuscular
      injection of turpentine on the epileptic phenomenon in genetically epileptic El
      mice. As parameters of epileptic seizure, seizure threshold (number of toss-ups
      to induce convulsion), duration of actual convulsion and duration of post actual
      convulsive period (period from the offset of convulsion to full recovery) were
      evaluated. The post actual convulsive period was prolonged without any change of
      seizure threshold or duration of actual convulsion 24 h after turpentine
      injection. Although pretreatment with indomethacin for one week did not change
      the seizure parameters, indomethacin suppressed the prolongation of the post
      actual convulsive period induced by turpentine. The mRNA expression of IL-1beta,
      IL-6 and COX-2 in the cerebral cortex was detected by RT-PCR. There was no
      difference in the mRNA expression in the cerebral cortex before and 24 h after
      seizure. The mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex were
      up-regulated 24 h after turpentine injection. On the other hand, the up-regulated
      mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex after turpentine
      treatment were not suppressed by indomethacin. These results suggest that
      prostaglandins induced with COX-2 in the cerebral cortex seem to play an
      important role in the maintenance of the post convulsive period, but not in
      induction and maintenance of the actual convulsive state.

PMID- 16981404
TI  - Distinction between steady-state inactivation and voltage-dependent facilitation
      in L-type Ca2+ channel alpha1c and alpha1c/beta subunits.
AB  - The L-type Ca2+ channel has a unique kinetic property known as voltage-dependent
      facilitation. Many researchers have repeatedly investigated the mechanism in
      response to the voltage-dependent facilitation since the first observation by
      Fenwick et al. in 1982. Electrophysiological evaluations of voltage-dependent
      facilitation, however, remain inconsistent, partially because of its unclear
      definition. Some scientists understand it as a current augmentation by a
      conditioning prepulse prior to the test pulse, and others understand it as a
      result of the U-shape steady-state inactivation curve. We therefore investigated
      to identify the distinction between the voltage-dependent facilitation and the
      steady-state inactivation, by use of Ba2+ as the charge in order to avoid the
      other inactivation mechanism or the Ca(2+)-dependent inactivation upon this
      analysis. Conventional whole-cell mode patch clamp technique was applied to
      chinese hamster fibroblast (CHW) cells that express the alpha1c subunit alone or
      the alpha1c subunit with the beta subunit (alpha1c/beta) derived from rabbit
      heart to investigate the voltage-dependent facilitation depending on the
      composition of the subunits. Coexpression of the beta subunit augmented alpha1
      subunit channel current and shifted current-voltage relation towards
      hyperpolarized direction. In the experiment using conventional double pulse
      protocol to investigate steady-state inactivation, alpha1c subunit channel
      current and alpha1c/beta subunit channel current were not fully inactivated.
      Subtraction of the steady-state inactivation component from whole recovered
      current enabled us to identify the voltage-dependent facilitation component of
      the L-type Ca2+ channel. The voltage-dependent facilitation of the alpha1 subunit
      current and the alpha1c/beta subunit current were identical in kinetics, and
      could be generated at 0 mV or depolarized potentials partially overlapped with
      the potential range for the steady-state inactivation of the current. These
      results suggest that the voltage-dependent facilitation of the L-type Ca2+
      channel could be formed by the alpha1c subunit without interaction with the beta
      subunit, and that the range for the voltage-dependent facilitation and the steady
      state inactivation overlap each other at 0 mV or more depolarized potentials up
      to approximately + 100 mV.

PMID- 16981405
TI  - [Hormone therapy for breast cancer].
AB  - Breast cancer is a hormone responsive disease, and its proliferation and
      progression correlate with estrogen. Estrogen binds to estrogen receptor and
      induces various target genes, thus promoting proliferation of breast cancer
      cells. Therefore, the strategy of endocrine therapy is the blockade of estrogen
      action. We can use a luteinizing hormone releasing hormone agonist and aromatase
      inhibitor as an interruptor of supply, tamoxifen as an inhibitor of estrogen
      receptor, and medroxyprogesterone acetate with an anti-estrogen action. In this
      article, we review endocrine therapy for breast cancer patients based on recent
      clinical trials.

PMID- 16981406
TI  - [Factors influencing student nurses' emotions toward children and their concept
      of motherhood].
AB  - The purpose of this study is to investigate the factors influencing the emotions
      of student nurses toward children in order to apply the results to their
      practical training, since the opportunity for contact with children has been
      decreasing in recent years due to the declining birth rate. 278 student nurses
      completed a self-administered anonymous questionnaire that consisted of their
      background, such as living with children and experience of contact with children,
      their learning process, such as finished lectures and nursing training in child
      and maternal care or not, 28 items from Hanazawa's scale of emotions toward
      children, and 27 items for the concept of motherhood. The obtained data was
      analyzed using the SPSS 12.0J for Windows with the Spearman's correlation
      coefficient, Mann-Whitney U test and Kruskal Wallis test. The valid recovery was
      121 (43.5%). The negative point for the concept of motherhood was significantly
      lower in the group that had finished nursing training in child and maternal care
      than in the group without such training. On the other hand, living with children
      and experience of contact with children did not influence their emotions toward
      children or concept of motherhood. The results of this study suggest that the
      experiences that student nurses have some deliberate and active contacts with
      children and mothers during their nursing training in child and maternal care
      have an influence on their concept of motherhood.

PMID- 16981407
TI  - [The instruction of the patient educational method in clinical nursing training:
      the actual condition of a student guidance case about diabetic's nursing using
      the diabetes retinopathy model].
AB  - We taught fourth-year students in a university about patient education using the
      diabetes retinopathy model in adult nursing practice. We analyzed teacher's
      student guidance plans and the guidance process using a clinical training
      education analysis form from the viewpoint of qualitative interpretation. We
      evaluated the degree of achievement of the students' goal for practice and the
      training subject. Consequently, the teacher developed training guidance as a
      class.

PMID- 16981408
TI  - [Change in awareness of waste reduction as observed among female students
      attending a college of nursing].
AB  - We conducted a survey from 1999 to 2004 of female students attending a college of
      nursing, regarding their awareness of the municipal waste reduction policy as
      well as the problems caused by dioxins. The questionnaire survey showed that over
      the six years a majority of students supported a stricter waste-sorting policy.
      The students were willing to sort waste in more minute details. Only a handful of
      students was aware of the municipal government's waste-reduction campaign.
      Furthermore, the students' awareness regarding problems caused by dioxins was
      high, but decreased from 94.7% in 1999 to 76.5% in 2004, with more than 90.0% of
      the students recognizing that it is necessary to reduce the total amount of waste
      in order to decrease dioxin emission from incineration plants.

PMID- 16981410
TI  - A plea for preservation.

PMID- 16981409
TI  - [Influence of inclusive child day-care on nursery school teachers: a
      questionnaire survey of teachers with experience in inclusive child day-care in K
      City].
AB  - The purpose of this survey questionnaire is to investigate the factors
      influencing how nursery school teachers perceive inclusive child day-care in K
      City in order to qualify what support we can provide. The questionnaire was sent
      to nursery school teachers with experience in inclusive child day-care in K City.
      Three hundred seventeen teachers provided sufficient data for analysis. The
      results of this survey suggest that teachers perceive inclusive child day-care to
      lead up to self-development and the pleasure of child-caring. On the other hand,
      they feel a burden of inclusive child day-care, with teachers in their 40 s
      feeling a stronger burden than teachers in their 20 s. And teachers with
      experience in taking care of emotionally disturbed children or teachers with
      experience in taking care of hearing-impaired children feel a stronger burden
      than teachers without experience in taking care of them. The results of our
      survey also suggest that it is necessary for support systems to have special
      knowledge about disabled children and special ways of caring, and to decrease
      teachers' burden or dissatisfaction with inclusive child day-care.

PMID- 16981411
TI  - Over (and behind) the counter. A deal is struck on selling the 'morning-after
      pill'--and a new FDA chief.

PMID- 16981412
TI  - A storm over warming. Are hurricanes linked to global warming?

PMID- 16981413
TI  - Conquering those growing pains.

PMID- 16981414
TI  - Not just for tots. Three new vaccines for older kids expand protection from
      disease.

PMID- 16981415
TI  - Obesity gets an early start.

PMID- 16981416
TI  - [What is the most effective approach to the reduction of cardiovascular risk in
      type-2 diabetes mellitus?].
AB  - It is well known that the target blood glucose values are not fulfilled in
      treatment of patients with type 2 diabetes mellitus. (UKPDS) The high mortality
      rate in type 2 diabetes mellitus is associated with the augmented cardiovascular
      risk. It is well documented, that the beneficial influence of high blood
      pressure, dyslipidaemia, and hypercoagulation compared to hyperglycaemia, is a
      more powerful approach in reduction of cardiovascular risk in type 2 diabetes
      mellitus. The effect of medical interventions on alteration of cardiovascular
      risk and glucose homeostasis is not always concordant: beta-blockers
      automatically reduce cardiovascular risk, but may result in deterioration of
      blood glucose values, sulfanylurea drugs effectively reduce hyperglycaemia, but
      could paradoxically increase the cardiovascular risk. The acarbose, metformin,
      thiazolidindione, fibric acid treatment improves the profile of vascular risk
      factors, additionally could have a beneficial metabolic effect resulting in
      reducing cardiovascular risk in patients with type 2 diabetes mellitus. IN
      CONCLUSION: the cardiovascular risk in type 2 diabetes mellitus can be most
      effectively influenced by reduction of high blood pressure, dyslipidaemia, and
      dysfunction of haemostasis. The improvement of glucose homeostasis is, novel
      medical interventions seem to be important tools in reducing cardiovascular risk
      in patients with type 2 diabetes mellitus.

PMID- 16981418
TI  - [Different clinical forms of adrenal abscess in two newborns].
AB  - Adrenal abscess is a rare disease in the neonatal period. The classical symptoms
      are abdominal mass, anaemia and prolonged jaundice which are associated with
      fever, vomiting and feeding difficulties. The authors present the histories of
      two mature, male newborns with adrenal hemorrhage, where the size of the masses
      increased progressively and finally adrenal abscesses were developed. The first
      case showed the classical symptoms of adrenal abscess, however, the antibiotic
      treatment led to complete remission of the symptoms and laboratory infectious
      markers, therefore the baby was discharged. In a few day later he became septic
      and was admitted again. This time he was operated on and a large abscess was
      evacuated, which contained about 60 ml of pus. After this intervention multi
      organ failure developed, but due to the intensive therapy the baby recovered. In
      the second newborn the increasing adrenal hemorrhage was accompanied by elevated
      infectious markers despite of the different antibiotic treatments, however, he
      showed no clinical signs of infection. Because of the discrepancies between the
      clinical and laboratory findings and also the imaging studies the possibility of
      neuroblastoma has also arisen. Urinary vanillylmandelic acid excretion was
      normal, but elevated neuron-specific enolase levels were measured. Surgical
      exploration was performed, pus was drained from the mass and anaerobic
      Bacteroides fragilis was cultured, therefore metronidazole therapy was started.
      After that the baby fully recovered.

PMID- 16981417
TI  - [Prevention of malignant tumors caused by human papilloma virus (HPV) by
      vaccination and with the methods of classical gynecologic diagnostics].
AB  - The "gold standard" of the gynecologic examinations is even today the classical
      clinical examination completed with the digital colposcopy, the Pap smears
      prepared from transport media and histological examination of biopsy material.
      Without these classical examinations one cannot evaluate the results of the
      molecular tests detecting papillomaviruses. The majority (70 to 90%) of the
      primary clinical symptoms caused by papillomaviruses recovers spontaneously. The
      recovery can be supported by, "imiquimod" (Aldara) which is an immunostimulant
      inducing interferon gamma and the production of interleukins, since
      papillomavirus infection is able to prevent the production of these mediators
      through its blocking effect to the innate immunity. Prevention is the main aim of
      the contemporary public health facilitated by the modern gene technology. The
      tetravalent vaccine (types 6, 11, 16 and 18) is harmless, since no tumor inducing
      genes are included. The empty capsids are manufactured in yeast cells and
      purified to a high degree similar to that of hepatitis B vaccine. The tetravalent
      vaccine is a preventive vaccine. It will be useful for teenagers, who have not
      acquired yet the most common papillomavirus types. There is intensive research
      going on in order to create therapeutic vaccines, that might be effective also in
      people of older age who had acquired certain virus types before vaccination, and
      may possess clinical symptoms, too. Men are the source of papillomavirus
      infection of women. Therefore vaccination of both genders will be indicated. The
      importance of the classical diagnostic procedures will not be diminished even
      under the umbrella of vaccination, since the preventive efforts were shown to be
      fully effective, if the clinical examinations, colposcopy, pap smears and
      biopsies are regularly performed in the patients with clinical symptoms
      increasing the rate of recovery above 90%. About 13 to 15 subtypes of human
      papillomaviruses may induce malignant processes. These are also present and most
      frequent in Hungary both in sexually transmitted infections and in the cancers of
      head and neck.

PMID- 16981419
TI  - [Fatty acid composition of human milk in mothers of preterm and full-term infants
      in the first three weeks of lactation].
AB  - INTRODUCTION: It is a classical question of infant nutrition whether fatty acid
      composition of human milk differs in mothers of preterm as compared to those of
      full-term infants. AIMS AND METHODS: The authors analysed fatty acid composition
      of milk samples obtained five times during the first month of lactation from
      mothers of preterm (n = 8, gestational age: 28.0 [4.2] weeks, birthweight: 1235
      [420] g, median [IQR]) and full-term (n = 10, gestational age: 38.5 [2.7] weeks,
      birthweight: 3375 [282] g) infants with high-resolution capillary gas-liquid
      chromatography. RESULTS: Maternal age, body mass index and eating habits of the
      mothers did not differ between the two groups. Neither did fat contents of human
      milk differ between the two groups. Values of linoleic (C18:2omega-6) and alpha
      linolenic (C18:3omega-3) acid did not differ. Values of arachidonic acid
      (C20:4omega-6) and docosahexaenoic acid (C22:6omega-3) were significantly higher
      following preterm as compared to full-term delivery. Values of the intermediary
      metabolites g-linolenic acid (C18:3omega-6), dihomo-gamma-linolenic acid
      (C20:3omega-6), octadecanotetraenoic acid (C18:4omega-3) and eicosatrienoic acid
      (C20:3omega-3) were also significantly higher in human milk samples of mothers of
      preterm as compared to those of full-term infants. CONCLUSION: Significantly
      higher contribution of long-chain polyunsaturated fatty acids in breast milk of
      mothers giving birth to preterm as compared to full-term infants supports the
      concept, that preterm infants would benefit more from feeding their own mothers
      milk than from receiving donor milk.

PMID- 16981421
TI  - [Diagnosis and surgical treatment of female stress incontinence].

PMID- 16981420
TI  - [Granulomatous hepatitis successfully treated with ursodeoxycholic acid].
AB  - The etiology of granulomatous hepatitis is extremely extensive for which the
      granulomatous reaction induced hepatic inflammation is characteristic. In the
      majority of cases it is part of a systemic disease but sometimes there is primer
      hepatic lesion in the background. The 21 year-old Caucasian female patient was
      taken to hospital having flu-like symptoms and icterus. While searching for the
      cause of her cholestatic hepatocellular lesion infections, tumors, storage
      diseases were excluded. However the root cause could not be identified. The
      histology showed granulomatous reaction, inflammation, intrahepatic bile duct
      proliferation and micronodular cirrhosis in the liver tissue. Taken it into
      consideration together with the the clinical picture and the laboratory findings
      primer sclerosing cholangitis was rendered probable. Her state deteriorated and
      even the necessity of liver transplantation emerged. The patient was treated with
      ursodeoxycholic acid which resulted in remission lasting for years now. Two years
      after the onset of the hepatic disease pancolitis ulcerosa with affection of the
      ileum terminalis was found in the patient which supports the diagnosis of primary
      sclerosing cholangitis.

PMID- 16981422
TI  - [Nutrition and cardiovascular mortality].
AB  - About 17 million persons die in cardiovascular disease yearly in the world. Most
      part of this disease can be prevented by the elimination of primary risk factors,
      thus by the abolishment of unhealthy nutrition, physical inactivity and by the
      absence of smoking. The cost-effective national program, as well as the life
      style with decreasing individual risk factors can give a trend to decrease the
      cardiovascular mortality. Individually the usual blood pressure and cholesterol
      control, the inhibition of obesity and the life style without smoking are able to
      decrease the organic changes, which produce the lethal consequences of this
      disease. The different kinds of diets can significantly influence the development
      of human diseases. The Western diet has atherogenic effect, increases the risk of
      myocardial infarction. The Mediterranean diet beneficially influences the life
      expectancy at birth. The Far-East Japanese diet could specially be important from
      the viewpoint of nutrition, because the longest life expectancy at birth and the
      smallest cardiovascular mortality can be found there. The quality nutrition
      factors (vitamins, vitamin like materials, polyphenols in wine and fruit juices,
      trace elements, omega-3 fatty acids) play an important role in the decreasing of
      oxidative stress and cardiovascular mortality.

PMID- 16981423
TI  - [Radiotherapy of pituitary tumours].
AB  - In this article, the role of conventional radiotherapy and radiosurgery in the
      management of pituitary tumors is discussed. After a brief review about the
      mechanism of action and different techniques of irradiation therapy, the
      therapeutic effectiveness and side effects are analysed in the various types of
      pituitary tumors. Conventional fractionated radiotherapy has long been used to
      control growth and/or hormonal secretion of residual or recurrent pituitary
      tumors. Nevertheless, there is still a controversy concerning patient selection
      for radiotherapy, because several potentially significant side effects including
      hypopituitarism may develop. Stereotactic radiosurgical methods may have several
      advantages over conventional radiotherapy; they can be applied, for example, in
      patients with residual or recurrent pituitary tumors who had previously received
      conventional radiotherapy. However, long-term follow-up data with these
      relatively new techniques are still limited.

PMID- 16981424
TI  - [Prevention of target organ damage with modern antihypertensive agents].
AB  - This review summarises the recent epidemiological data on hypertension, the aims
      of the treatment of hypertension, and emphasizes the importance of the
      modification of target organ damages and accelerated clinical conditions. Because
      the pathogenesis of hypertension is extremely complex, the therapy most likely
      requires a combined drug administration. The modern third generation
      dihydropyridine calcium channel blocker, amlodipine, not only has a favourable
      antihypertensive and anti-ischemic effect, but anti-atherosclerosis properties as
      well. There are plenty of evidence which demonstrate that lisinopril, a first
      line antihypertensive agent, has a positive effect in the treatment of left
      ventricular hypertrophy, retinopathy and nephropathy, and also has a favourable
      outcome after myocardial infarction and in heart failure. The combined
      administration of the two drugs leads to a favourable additive effect, with a
      decrease in the number and severity of side effects. The results of the ASCOT
      study proved a favourable effect with amlodipine based, combination therapy with
      an ACE-inhibitor, compared with the traditional beta-blockers and diuretics. The
      data of the CAFE sub-study showed, that in spite of the similar peripheral
      antihypertensive effect, the amlodipine based therapy decreased the central
      aortic pulse pressure to a greater extent. The central aortic pressure showed a
      good correlation with the end-points of the study, respectively. The results of
      the Hungarian multicenter study (HAMLET) proved the effective and safe
      administration of the two drugs in combination. Based on the above evidence, the
      fixed-dose combination of the CCB-ACE inhibitor (amlodipine-lisinopril) has not
      only effective blood pressure reducing properties, but also results in
      cardiovascular risk reduction, good tolerability and favourable compliance.

PMID- 16981425
TI  - [Changes of the different neuropeptide containing nerve elements in the inflamed
      human gall bladder].
AB  - BACKGROUND, AIMS: The changes of different neuropeptide containing nerve elements
      might play a role in the pathogenesis of cholecystitis and the formation of
      gallstones, therefore the authors have investigated the density of the
      neuropeptide containing nerve fibres and immunocompetent cells in human
      gallbladder (control and cholecystitis). METHODS: The different neuropeptide
      containing nerve elements and immunocytes were detected by avidin-biotin
      peroxidase (ABC) immunohistochemistry. RESULTS: In the control gallbladder the
      density of the different neuropeptide containing nerve fibres showed different
      pattern in all layers. In the inflamed gallbladder the number of the vasoactive
      intestinal polypeptide (VIP) positive nerve fibres increased significantly, very
      dense immunoreactive (IR) nerve fibres were located mainly in the tunica mucosa
      just below the epithelial lining. The number of the VIP IR nerve cell bodies was
      also increased. However, the number of the substance P (SP) IR nerve fibres was
      decreased significantly in the cholecystitis. The number of the neuropeptide Y
      (NPY) nerve fibres showed no changes, while their distribution was altered
      compared to the control. In the inflamed area the number of immunocompetent cells
      was strongly increased (being granulocytes, lymphocytes, plasma cells and mast
      cells) and some of them were also immunoreactive for SP, calcitonin gene-related
      peptide (CGRP) and VIP. Close contacts were detected between IR nerve fibres and
      the immunocytes in several cases. CONCLUSIONS: During inflammation the changes of
      the neuropeptide containing nerve fibres might alter the function (causing
      dilation) of the gall bladder, the activated immunocytes can also synthesize
      neuropeptides (SP, CGRP, VIP), so the released materials (cytokines, chemokines,
      histamine, as well as neuropeptides) might act in an autocrine and/or paracrine
      way influencing the function of the organ and of the immune system.

PMID- 16981426
TI  - [Head protection and cranial injury in the middle ages].

PMID- 16981427
TI  - [Rehabilitation and balneotherapy, wellness--2004].

PMID- 16981428
TI  - [Puccini--physicians, personages, illnesses, passion and destiny].

PMID- 16981429
TI  - The inhibitory action of long-chain fatty acids on the DNA binding activity of
      p53.
AB  - The in vitro relationship between human p53 DNA binding domain (p53 DBD) and FA
      was investigated. We found that saturated and monounsaturated long-chain FA
      inhibited the double-stranded DNA (dsDNA) binding activity of p53 DBD. The
      strongest inhibitors of saturated and unsaturated FA were docosanoic acid (22:0)
      and cis-12-heneicosenoic acid (21:1n-9), respectively. n-Octadecane, trans
      unsaturated FA, and FAME had no influence on the binding activity of p53 DBD,
      showing that the FA structures such as one or no double bond of cis
      configuration, hydrocarbon chain of length C20 to C22, and free carboxyl groups
      are important for the inhibition. The inhibitory effect of the R248A mutant of
      p53 DBD by saturated FA was as strong as that for wild-type p53 DBD. On the other
      hand, the inhibition of dsDNA binding activity of the same mutant by the cis
      configuration of monounsaturated FA was weaker than that for the wild type. These
      results suggest that R248 in p53 DBD is important for binding to monounsaturated
      FA. This is the first report that long-chain FA act as a dsDNA binding inhibitor
      of p53, and it could be considered that FA in the cell membrane might regulate
      the activity of p53 for cell division, cell-cycle checkpoint, and tumor
      suppression.

PMID- 16981430
TI  - Low-density lipoproteins are more electronegatively charged in type 1 than in
      type 2 diabetes mellitus.
AB  - Multifactorial etiology is involved in premature atherosclerosis related to
      diabetes. Most of the mechanisms that are responsible for the etiology in
      diabetes have remained unsolved so far. Type 1 diabetes is associated with a
      favorable lipid pattern and with microangiopathy, which is not true for type 2
      diabetes, which is related to dyslipidemia and macroangiopathy. The aim of this
      work was to evaluate the degree of LDL modification related to the types of
      diabetes. The question is whether the LDL could be differently modified since the
      pathogenesis of type 1 and type 2 diabetes is different. Thirty-one type 1 (19
      male and 12 female) and thirty type 2 (18 male and 12 female) diabetic patients
      were included in this study. Isolated LDL was analyzed by capillary
      electrophoresis for diene conjugate content and for electronegativity. LDL from
      type 1 diabetes subjects showed the highest electrophoretic mobility (P = 0.000).
      Instead, the diene conjugates contents were higher in the type 2 patients with
      HbA1c levels > 8% (P = 0.007). In conclusion, the increased diene content in type
      2 diabetic subjects in poor glycemic control and the highest LDL mobility found
      in type 1 subjects show that the LDL undergoes different modifications. In type 2
      patients, electronegative LDL are in a state of higher susceptibility to
      oxidation, whereas in type 1 subjects the finding of electronegative lipoproteins
      could provide an index of the relative atherogenicity of circulating LDL,
      especially as LDL has higher electrophoretic mobility than normal subjects.

PMID- 16981431
TI  - Dietary fatty acids early in life affect lipid metabolism and adiposity in young
      rats.
AB  - The purpose of this study was to evaluate the effects of four isoenergetic diets
      of differing fat composition on blood lipid profile and adiposity in young rats.
      Diets containing different lipid sources--partially hydrogenated vegetable oil
      (PHVO), palm oil (PO), canola oil (CO), and soy oil (SO)--were fed to lactating
      rats during the 21 days of lactation, and then fed to young males following
      weaning until the 45th day of life. In vivo lipogenesis rate (LR), lipid content
      (LC), relative level of FA, and the activity of lipoprotein lipase (LPL) enzyme
      were measured in epididymal adipose tissue (EPI). Fasting blood lipoproteins and
      LC in the carcass were also appraised. Body weight of PO and PHVO groups was
      significantly higher than CO and SO groups from day 14 of lactation to day 45,
      despite the lower food intake in the PHVO group. PO and PHVO groups presented
      higher LR and LC in EPI than SO and CO groups. Carcass fat content was
      significantly higher in PHVO and PO groups than in CO and SO groups. The LPL
      activity in EPI was unaffected by dietary lipids. PHVO group had increased total
      cholesterol and TAG concentrations in comparison with the PO group, and
      significantly lower HDL level compared with the other groups. These results show
      that the kind of FA in the dietary lipid offered early in life can affect lipid
      metabolism and adiposity.

PMID- 16981432
TI  - Mice raised on milk transgenically enriched with n-3 PUFA have increased brain
      docosahexaenoic acid.
AB  - The brain contains high levels of the long-chain n-3 FA DHA (22:6n-3), mainly in
      the gray matter and synaptosomes. Adequate intake of DHA is crucial for optimal
      nervous system function, particularly in infants. Supplementation of infant
      formulas with DHA at levels similar to human breast milk is recommended for
      biochemical and functional benefits to neonates. We generated transgenic mice
      that produce elevated levels of n-3 PUFA in their milk by expressing the
      Caenorhabditis elegans n-3 FA desaturase under the control of a lactation-induced
      goat beta-casein promoter. To examine the postnatal effects of consuming the n-3
      enriched milk, we compared the growth and brain and plasma FA composition of
      mouse pups raised on milk from transgenic dams with those observed for pups
      raised on milk from nontransgenic dams. A significant decrease in arachidonic
      acid (ARA, 20:4n-6) and concomitant increases in n-3 PUFA were observed in the
      phospholipid fraction of transgenic mouse milk. The n-6:n-3 FA ratios were 4.7
      and 34.5 for the transgenic and control milk phospholipid fractions,
      respectively. DHA and DPA (22:5n-6) comprised 15.1% and 2.8% of brain FA from
      weanling mice nursed on transgenic dams, as compared with 6.9% and 9.2% for
      weanling mice nursed on control dams, respectively. This transgenic mouse model
      offers a unique approach to disassociate the effects and fetal programming
      resulting from a high n-6:n-3 FA ratio gestational environment from the postnatal
      nutritional effects of providing milk with differing n-6:n-3 FA ratios.

PMID- 16981433
TI  - Solubility in and affinity for the bile salt micelle of plant sterols are
      important determinants of their intestinal absorption in rats.
AB  - Intestinal absorption of various plant sterols was investigated in thoracic duct
      cannulated normal rats. Lymphatic recovery was the highest in campesterol,
      intermediate in brassicasterol and sitosterol, and the lowest in stigmasterol and
      sitostanol. Higher solubility in the bile salt micelle was observed in
      sitosterol, campesterol, and sitostanol than in brassicasterol and stigmasterol.
      The solubility of the latter two sterols was extremely low. When the affinity of
      plant sterols for the bile salt micelle was compared in an in vitro model system,
      which assessed sterol transfer from the micellar to the oil phase, the transfer
      rate was the highest in brassicasterol, intermediate in campesterol and
      stigmasterol, and lowest in sitosterol and sitostanol. Although no significant
      correlations between lymphatic recovery of plant sterols and their micellar
      solubility or transfer rate from the bile salt micelle were observed, highly
      positive correlation was obtained between the lymphatic recovery and the
      multiplication value of the micellar solubility and the transfer rate. These
      observations strongly suggest that both solubility in and affinity for the bile
      salt micelle of plant sterols are important determinants of their intestinal
      absorption in rats.

PMID- 16981434
TI  - Diacylglycerol acyltransferases from Vernonia and Stokesia prefer substrates with
      vernolic acid.
AB  - Genetic engineering of common oil crops for industrially valuable epoxy FA
      production by expressing epoxygenase genes alone had limited success. Identifying
      other key genes responsible for the selective incorporation of epoxy FA into seed
      oil in natural high accumulators appears to be an important next step. We
      investigated the substrate preferences of acyl CoA:diacylglycerol
      acyltransferases (DGAT) of two natural high accumulators of vernolic acid,
      Vernonia galamensis and Stokesia laevis, as compared with a common oilseed crop
      soybean. Developing seed microsomes were fed with either [14C]oleoyl CoA or [14C]
      vernoloyl CoA in combinations with no exogenous DAG or with 1,2-dioleoyl-sn
      glycerol, 1-palmitoyl-2-vernoloyl-sn-glycerol, 1,2-divernoloyl-sn-glycerol, 1,2
      dioleoyl-rac-glycerol, or 1,2-divernoloyl-rac-glycerol to determine their
      relative incorporation into TAG. The results showed that in using sn-1,2-DAG, the
      highest DGAT activity was from the substrate combination of vernoloyl CoA with
      1,2-divernoloyl-sn-glycerol, and the lowest was from vernoloyl CoA or oleoyl CoA
      with 1,2-dioleoyl-sn-glycerol in both V. galamensis and S. laevis. Soybean DGAT
      was more active with oleoyl CoA than vernoloyl CoA, and more active with 1,2
      dioleoyl-sn-glycerol when oleoyl CoA was fed. DGAT assays without exogenous DAG,
      or with exogenous sn-1,2-DAG fed individually or simultaneously showed consistent
      results. In combinations with either oleoyl CoA or vernoloyl CoA, DGAT had much
      higher activity with rac-1,2-DAG than with their corresponding sn-1,2-DAG, and
      the substrate selectivity was diminished when rac-1,2-DAG were used instead of sn
      1,2-DAG. These studies suggest that DGAT action might be an important step for
      selective incorporation of vernolic acid into TAG in V. galamensis and S. laevis.

PMID- 16981436
TI  - One-step analysis of major bile components in human bile using 1H NMR
      spectroscopy.
AB  - Human gallbladder bile dissolved in dimethylsulfoxide provides sharp and resolved
      signals for major bile components in 1H NMR spectra. Characteristic well-resolved
      marker signals that invariably appear in 1H NMR spectra of bile were identified
      for cholesterol (H18 methyl signal at 0.643 ppm), lipids (glycerol CH signal at
      5.064 ppm), total bile acids (H18 signals in the range 0.520-0.626 ppm), total
      glycine conjugated bile acids (NH signal at 6.958 ppm), total taurine conjugated
      bile acids (NH signal at 7.646 ppm), and urea (NH2 signal near 5.48 ppm), which
      enabled their rapid and accurate analysis. Excellent linearity and precision of
      quantitative analysis was observed for all the identified bile components (R2 >
      0.99 for all). The method was demonstrated on gallbladder bile from 19 patients
      with gallbladder diseases. Urea in bile was identified by NMR for the first time
      and its quantitative analysis, along with several other bile components, is
      presented. The majority of the bile components could be analyzed in a single
      step. Accurate and rapid quantification of several bile components noninvasively
      by using the method presented herein may have far-reaching implications in the
      study of bile acid metabolism and pathophysiology of various hepatobiliary and
      gastrointestinal diseases.

PMID- 16981435
TI  - Impact of 20:4n-6 supplementation on the fatty acid composition and hemocyte
      parameters of the Pacific oyster Crassostrea gigas.
AB  - Arachidonic acid (20:4n-6, ArA) and its eicosanoid metabolites have been
      demonstrated to be implicated in immune functions of vertebrates, fish, and
      insects. Thus, the aim of this study was to assess the impact of ArA
      supplementation on the FA composition and hemocyte parameters of oysters
      Crassostrea gigas. Oyster dietary conditioning consisted of direct addition of
      ArA solutions at a dose of 0, 0.25, or 0.41 microg ArA per mL of seawater into
      tanks in the presence or absence of T-Iso algae. Results showed significant
      incorporation of ArA into gill polar lipids when administered with algae (up to
      19.7%) or without algae (up to 12.1%). ArA supplementation led to an increase in
      hemocyte numbers, phagocytosis, and production of reactive oxygen species by
      hemocytes from ArA-supplemented oysters. Moreover, the inhibitory effect of
      Vibrio aestuarianus extracellular products on the adhesive proprieties of
      hemocytes was lessened in oysters fed ArA-supplemented T-Iso. All changes in
      oyster hemocyte parameters reported in the present study suggest that ArA and/or
      eicosanoid metabolites affect oyster hemocyte functions.

PMID- 16981437
TI  - Single-step analysis of individual conjugated bile acids in human bile using 1H
      NMR spectroscopy.
AB  - 1H and 13C NMR spectra of intact human bile were assigned using one-dimensional
      (1H and 13C) and two-dimensional (1H-1H and 1H-13C) experiments. Individual
      conjugated bile acids--glycocholic acid, glycodeoxycholic acid,
      glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and
      taurochenodeoxycholic acid--were identified. The bile acids were quantified
      accurately and individually in a single step by using distinct and characteristic
      amide signals. Making use of 13C NMR, the study also suggests a way to analyze
      unconjugated bile acids separately, if present. Chemical shift assignments and
      rapid single-step analysis of individual conjugated bile acids from intact bile
      presented herein may have immense utility in the study of bile acid metabolism
      and deeper understanding of hepatobiliary diseases.

PMID- 16981438
TI  - Accelerated solvent extraction for quantitative measurement of fatty acids in
      plasma and erythrocytes.
AB  - Consumption of fish rich in n-3 highly unsaturated FAs (i.e., EPA and DHA) has
      been suggested to decrease the risk of lifestyle-related diseases such as
      coronary heart disease, cancer, diabetes, and dementia. Blood levels of those FA
      are known appropriate biomarkers of both the corresponding dietary FA intakes and
      fish consumption. In place of traditional handwork methods for extracting FA, we
      performed an accelerated solvent extraction (ASE) for at least 13 selected FA in
      plasma and erythrocytes to measure them by GLC. The FA levels (concentrations and
      compositions) in 35-50 microL of plasma or erythrocytes were extracted by ASE and
      measured by GLC. Intra- and interassay coefficients of variation were < or = 6.0%
      for both blood materials, except with a minor group of FA (< or = 1.0% of total
      FA). When ASE was compared with two traditional handwork methods, FA levels in
      plasma from 18 healthy subjects were all coincident with very high Pearson's
      correlation coefficients for the three sets of the same 18 samples (r > or = 0.85
      to 0.95, P < 0.0001), except for 18:0 (r = 0.59, P < 0.01). Using ASE and GLC, we
      have developed a new method for determination the levels of FA in plasma and
      erythrocytes as biomarkers for dietary intake of fish, fat, and FA. This new
      method makes it feasible to measure small volumes of samples, automatically,
      quantitatively, routinely, easily, rapidly and cheaply, with acceptable precision
      and accuracy.

PMID- 16981439
TI  - HPLC method for quantification and characterization of cholesterol and its
      oxidation products in eggs.
AB  - A new method was developed for the simultaneous determination of cholesterol and
      its oxidation products in eggs, using HPLC with UV and refractive index (RI)
      detectors, and HPLC interfaced with atmospheric pressure chemical ionization
      coupled to MS (HPLC-APCI-MS). The best conditions for direct saponification of
      the sample and extraction of the non-saponifiable material were defined using
      complete factorial designs with central points. The method showed accuracy and
      precision with a detection limit between 0.002 and 0.079 microg/g. The oxides
      cholest-5-ene-3beta,20alpha-diol and cholest-5-ene-3beta,25-diol identified by
      HPLC-UV-RI were not confirmed by HPLC-APCI-MS.

PMID- 16981440
TI  - Identification and production of n-8 odd-numbered polyunsaturated fatty acids by
      a delta12 desaturation-defective mutant of Mortierella alpina 1S-4.
AB  - A mutant of Mortierella alpina, JT-180, which is defective in its delta12
      desaturase activity but exhibits enhanced activities of delta5 and delta6
      desaturases, produced a high proportion (up to 80%) of odd-chain FA when grown on
      3% n-heptadecane. Following growth of the mutant on n-heptadecane, three unusual
      odd-chain fatty acyl residues were identified as 6,9-heptadecadienoic acid
      (17:2), 8,11 -nonadecadienoic acid (19:2), and 5,8,11-nonadecatrienoic acid
      (19:3) by means of GC-MS, MS-MS, and NMR analyses. The mycelial contents of these
      FA reached 20.3, 3.6, and 5.8 mg/g dry mycelia, respectively, when it was
      cultivated in medium comprising 4% (vol/vol) n-heptadecane and 1% (wt/vol) yeast
      extract, pH 6.0, at 28 degrees C for 7 d. The biosynthetic route (n-8 route) to
      19:3 was presumed to mimic the n-9 route to Mead acid (20:3n-9) in mammals: 17:0 
      -> 9-17:1 --> 6,9-17:2 --> 8,11-19:2 --> 5,8,11-19:3.

PMID- 16981441
TI  - Emerging technologies and the safety and health of farming people.

PMID- 16981442
TI  - Protecting young workers in agriculture: participation in tractor certification
      training.
AB  - Tractor-related injuries among youth are an important public health problem. The
      major objectives of this study were to (1) provide a rigorous estimate of the
      number of youth operating tractors in Ohio and (2) assess the extent to which
      these youth are participating in federally mandated tractor safety training. A
      self-administered questionnaire was completed by approximately 4,000 students
      ages 14 or 15 years who were enrolled in a stratified cluster sample of 99 Ohio
      schools. Almost one-third of the youth (30%) reported having operated tractors,
      with 19% having operated a tractor on a farm not owned by a parent or guardian.
      More than half of the youth (52%) reported having operated a tractor and/or other
      hazardous machinery, with 25% having operated the machinery on a farm not owned
      or operated by a parent or guardian. Extrapolating from 4-H records and Ohio
      census data, fewer than 1% of the youth who are operating tractors or other
      hazardous machinery have participated in tractor certification training.
      Increasing participation in mandated training may be an important step in
      protecting the health of our nation's young agricultural workers.

PMID- 16981443
TI  - An investigation of three physical parameters of PTO entanglements.
AB  - The PTO driveline is the most common means of transferring power from a tractor
      to towed machinery and stationary equipment. While equipment manufacturers
      install shielding to protect operators and bystanders from coming in contact with
      operating PTO components (particularly around the knuckle), entanglement is still
      a cause of some of the most catastrophic agricultural work-related injuries. This
      study investigated the influence of material type, material length, and angle of
      material introduction on entanglements with a spinning PTO shaft knuckle. These
      variables were tested using a laboratory PTO apparatus where 165 entanglements
      were recorded during the 720 trials conducted. The results indicate that lighter
      materials, such as cotton thread, have a significantly higher probability of
      becoming entangled than heavier materials, such as leather bootlaces. Materials
      that were longer (i.e., extend further below the midline of the PTO knuckle) have
      higher probabilities of becoming entangled than do shorter materials. The
      horizontal path that the material traveled across the centerline of the PTO shaft
      impacted the probability of entanglement. When the angle of intersection of the
      horizontal path of travel relative to the centerline of the PTO shaft is 90
      degrees, or close to 90 degrees, a higher probability of entanglement occurs. All
      165 entanglements occurred on the downward rotational side of the PTO knuckle
      regardless of which side the horizontal path of travel started from. The results
      of this study provide the first look at understanding the physical phenomena
      associated with the initial stages of PTO entanglements and set the stage for
      future research.

PMID- 16981444
TI  - Rollover protection on New York tractors and farmers' readiness for change.
AB  - Tractor overturns contribute significantly to fatalities in New York State
      agriculture. On-site inspections a decade ago indicated that approximately 60% of
      tractors were without effective rollover protection. Our objectives were: to
      describe the current prevalence and distribution of rollover protective
      structures (ROPS) on New York farm tractors, to identify characteristics
      associated with the absence of ROPS, to explore segmenting the New York farm
      community on readiness for ROPS retrofitting, and to identify demographic
      characteristics that might assist in this segmenting. A random selection of 644
      livestock, dairy, fruit, cash crop, vegetable, and organic farms were contacted
      for a telephone survey. Of 562 farms (87%) participating, 102 (18.1%) had all
      tractors equipped with ROPS and 138 (24.6%) had none. A disproportionate number
      of livestock, cash crop, and organic operations had no ROPS. Rates of ROPS
      equipped tractors correlated directly with farm size and annual hours of tractor
      operation. Older farmers had a lower proportion of ROPS tractors. The presence of
      a child operator did not affect the proportion of ROPS tractors. After weighting
      the sample, the total number of non-ROPS tractors in New York is estimated at
      more than 80,000. In addition to providing key farm demographics, the survey
      enabled placement of farmers on a "stage of change" continuum related to
      readiness for retrofitting. Three-quarters of New York farmers are in the
      "precontemplation" stage of change relative to ROPS retrofitting, and this varies
      little by size of operation, age of farmer, or the presence of child tractor
      operators. Stage of change may relate to hours of tractor operation (p = 0.05)
      and does relate to commodity (p = 0.003) due primarily to the higher proportion
      of crop farmers in the earliest stage of change. The goal of retrofitting all New
      York farm tractors with ROPS appears nearly as daunting as it did a decade ago.

PMID- 16981445
TI  - Risk perceptions, barriers, and motivators to tractor ROPS retrofitting in the
      New York state farm community.
AB  - The prevalence of tractor rollovers among agricultural workers has made the
      retrofitting of tractors with rollover protective structures (ROPS) and seat
      belts a public health priority for agricultural health and safety specialists. To
      address this concern, the New York Center for Agricultural Medicine and Health
      (NYCAMH) developed a seven-question survey, designed to assess perceptions of
      risk as well as potential motivators and barriers to retrofitting. Data from 465
      phone surveys were gathered from New York State farmers representing various
      commodities and farm sizes. Analysis of responses to three qualitative questions
      contained in the survey indicated that most farmers in New York understand the
      importance of ROPS but lack the proper motivation to consider retrofitting. It
      appears that more convenient safety strategies, cost, and age of the tractor
      compete with a farmer's initiative to retrofit. In addition, survey responses
      illustrate that although many farmers believe ROPS are important in a general
      sense, many believe that this safety measure is not necessary for them in
      particular. Frequent motivators to retrofitting are concerns about safety,
      although the authors conclude that a more thorough analysis of these "general
      safety concerns" in qualitative interviews is important.

PMID- 16981446
TI  - Psychological determinants of behaviors leading to occupational injuries and
      diseases in agriculture: a literature overview.
AB  - Agriculture is one of the most hazardous occupational sectors, with a high
      prevalence of occupational injuries and work-related health problems. Most of
      these problems are caused by the interplay of human behavior and ergonomic
      factors and are thus preventable. Interventions to prevent occupational injuries
      and diseases among agricultural workers should aim to change risk behaviors and
      conditions by addressing specific behavioral determinants. To identify these
      factors, social cognitive models can be use that explain and predict health
      related behavior. This study reviews the literature on the application of social
      cognitive models for the prevention of occupational injuries and diseases among
      agricultural workers. Studies are reviewed that apply the Health Belief Model,
      Theory of ReasonedAction, Theory of Planned Behavior, Transtheoretical Model of
      Change, or their subcomponents, to predict or change preventive behavior. Only a
      limited number of studies were found describing interventions that make use of
      these models, and those that do are often poorly documented with regard to the
      effect sizes and the explanatory or predictive value. It is concluded that the
      application of social cognitive models could significantly contribute to the
      effectiveness of preventive interventions in agriculture.

PMID- 16981447
TI  - [Analysis of RAPD on medicinal plants of Codonopsis pilosula].
AB  - OBJECTIVE: To study genetic diversity and genetic relationship among 9 cultivated
      and 4 nature populations of Codonopsis pilosula and C. pilosula var. modesta form
      Gansu Province at DNA level. METHODS: DNA of 217 individuals was amplified by 14
      decamer primers from 200 radom primers. The polymorphic bands of RAPD were
      counted. And the results were analyzed by clustering analysis NTSYS-PC software.
      RESULTS: A total of 125 loci were detected by 14 arbitrary primers, among which
      109 and 106 loci were polymorphic in C. pilosula and C. pilosula var. modesta
      respectively, and the percentage of polymorphic bands (PPB) were 87.20% and 84.
      80%. The cluster analysis showed that 13 populations were divided into 2 groups.
      The one included 8 cultivated populations of C. pilosula, the other group
      consisted of a cultivated population and 4 nature populations of C. pilosula var.
      modesta. CONCLUSION: The RAPD results indicated that there was abundant genetic
      diversity in cultivated populations of C. pilosula and C. pilosula var. modesta.
      The genetic differentiation among 8 cultivated populations of C. pilosula was
      very small and related to their geographical distance. Only the cultivation in
      Wen County originated from C. pilosula var. modesta, while the other populations
      cultivated in Gansu Province belongs to C. pilosula.

PMID- 16981449
TI  - [Analysis of total alkaloids in Meconopsis quintuplinervia from different
      localtites of Qinghai].
AB  - The contents of total alkaloids in Meconopsis quintuplinervia Regel, grown in the
      different localtites of Qinghai Province, are detected by the method of
      spectrophometry. The result showed that total alkaloid in different localities
      were 0. 0262% to approximately 0.0788% , its mean was 0.0502%. The content of
      total alkaloids in the herb increased with elevation, not with latitude.

PMID- 16981448
TI  - [Effects of water stress on the growth of Lonicera japonica and quality of
      honeysuckle].
AB  - OBJECTIVE: Effects of water stress on the growth of Lonicera japonica and quality
      of honeysuckle were studied. METHODS: Different extent water stress treatment
      imposed to potted plants before the first florescence of honeysuckle, and the
      growth and related physiological indexes of Lonicera japonica were determined.
      RESULTS: Shoot grow slowly as well as the increases of specific weight of leaf
      and the decrease of the yield of honeysuckle under water stress. The contents of
      chlorophyl in the leaves treated water stress all increased, and the content of
      soluble suger had a rising stream. The content of soluble protein in leaves of
      plant imposed by minor stress treatment was obviously higher than that of CK and
      severe stress treatment. As the stress was hard, the content of proline in leaves
      increased significantly. With water stress severing, the content of chlorogenic
      acid in the flower bud decreased very significantly than CK. CONCLUSION: Water
      condition was a important factor affected the growth and development of shoots,
      leaves and flower buds as well as the quality of honeysuckle. In the cultivation
      of Loniccra japonica, irrigation timing and certain irrigation condition was
      necessary.

PMID- 16981450
TI  - [The morphological and histological identification of Chukrasia tabularis].
AB  - In this paper the descriptions and microscopic characters of Chukrasia tabularis
      were reported. The results provided scientific evidences for recognition and
      resources utilization.

PMID- 16981451
TI  - [Pharmacognostic studies on Begonia sinensis rhizome].
AB  - OBJECTIVE: To establish the characteristic method of rude medicinal material of
      rhizome of Begonia sinensis. METHOD: The characteristic features of the rhizome
      were studies by morphological and microscopic observation. RESULTS: The
      description and transverse features of transverse section of the rhizome were
      described, and in the powder the microscopic features such as cluster needle
      crystals, tentacle, ring-thread vessel were found. CONCLUSION: The
      characteristics can be used to differentiate the rhizome of Begonia sinensis.

PMID- 16981452
TI  - [Study on chemical constituents of Cyclocarya paliurus].
AB  - Phytochemical investigation of chemical constituents of the CHCl3 fraction of 75%
      alcohol extract from the leaves of Cyclocarya paliurus has resulted in the
      isolation of five compounds, alpha-boswellic (I), beta-boswellic (II), Oleanolic
      acid (III), 4-hydroxyl-3-methoxyl-benzoic acid (IV) and 3,6,3',5'-tetramenthox
      5,7,4'-trihydroxy-flavonol (V). Their structures were elucidated on the basis of
      spectroscopic analyses, especially NMR. Compunds I, II, IV and V were obtained
      from this plant for the first time.

PMID- 16981453
TI  - [Determination of istanbulin A in Sarcandra glabra].
AB  - OBJECTIVE: To determine istanbulin A in Sarcandra glabra (Thunb.) Nakai. METHODS:
      An RP-HPLC method was established and an hypersil ODS C18 column (4.6 mm x 200
      mm, 5 microm) was used. The detective wavelength was at 218nm. RESULTS:
      Istanbulin A had a good linearity in the range of 0. 135 to approximately 2. 16
      microg. The recovery rate was 98.54%. CONCLUSION: This method is simple, accurate
      and repeatable. It can be used to determine istanbulin A in Sarcandra glabra.

PMID- 16981454
TI  - [Determination of sulphur dioxide in commonly used Chinese herbal medicines with
      both food and medicine function for health care by ion-chromatographic method].
AB  - OBJECTIVE: To dertermine SO2 in Chinese herbal medicine with both food and
      medicinal functions. METHODS: A distilling and ion-chromatorgraphic method was
      applied. RESULTS: The results indicated that among 32 commonly used Chinese
      herbal medicines, 26 samples contained sulphur dioxide, varying in its contents
      and up to 3180 microg/g. The amount of sulphur dioxide did not change much after
      samples were washed by water. On the other hand, sulphur dioxide contents
      decreased after samples were exposed outdoor or boiled in water. CONCLUSION: The
      method was simple, accurate and reproducible.

PMID- 16981455
TI  - [Determination of capsaicin in Pheretima aspergillum from different habitats by
      RP-HPLC].
AB  - OBJECTIVE: To determine the content of hypoxanthine in Pheretima aspergillum from
      different habitats. METHOD: A RP-HPLC method was established. The chromatographic
      column was Inertsil ODS-EP. The mobile phase was H2O-CH3OH-C4H8O(93:: 7: 0.05).
      The flow rate was 1.0 ml/min, and the detection wavelength was 254 nm. RESULTS:
      The average recoveries for hypoxanthine was 98.6% , precision of the method was
      0. 50% (RSD, n = 6). CONCLUSION: The method can be used to determine the content
      of hypoxanthine in Pheretima aspergillum from diffrent habitats.

PMID- 16981456
TI  - [Determination of 5F in Pteris semipinnata L. from various origins by TLC
      scanning].
AB  - OBJECTIVE: To determine the content of 5F in Pteris semipinnata L. from various
      origins. METHODS: 5F was determined by TLC-Scanning. RESULTS: The linear
      relationship was in range of 0. 504 - 2. 520 microg. The mean recovery was 96.
      68% and RSD = 1.24% (n = 5). CONCLUSION: The method is available with a good
      reproducibility, and pretreatment is simple and easy to operate.

PMID- 16981457
TI  - [Effect of extract components from Plastrum testudinis and their combination
      component on proliferation of rat mesenchymal stem cell in vitro].
AB  - OBJECTIVE: To observe the effect of extract components from Plastrum Testudinis
      and their combination component on the proliferaiton of mesenchymal stem cell
      (MSC) to screen out the effective components. METHODS: Mesenchymal stem cells
      were dissociated from bone marrow of rat and were marked by Brdu, and the
      expression of CD44, CD54 and double label of Brdu and CD44 extract components (A
      to approximately J) with different concentration (2 microl, 5 microl,10 microl,20
      microl)added to cultured MSC. The cell viability was tested by MTT. RESULTS: Cell
      viability in component A, B, H, I with 20 microl, C, F with 10 microl and J with
      5 microl concentration group increased compared with that in control group (P <
      0.05) and cell viability in compponent E with 2 microl to approximately 20 microl
      concentration groups decreased compared with that in control group (P < 0.05).
      Cell viability in component D and G with 2 microl to approximately 20 microl
      concentration groups was similar to that in control group. Cell viability in
      combination component with J component increased, but cell viability in
      combination component with E component decrased. CONCLUSION: All compoents A,
      B,C,F, H, I and J can improve proliferation of MSC. Anong them, component J and
      its combination are the best. Component E and its combination can inhibit
      proliferation. But component D and G have no effect on proliferation of MSC.

PMID- 16981458
TI  - [Anti-proliferation effect of serum containning WEI KANG NING on gastric cancer
      MGC-803 cells and its mechanism].
AB  - OBJECTIVE: To investigate the anti-proliferation effect of WEI KANG NING on
      gastric cancer. METHODS: MGC-803 cells were cultured in different concentrations
      of serum containning WEI KANG NING. The inhibitory ratio of the cells was
      measured by MTT assay. Apoptosis was observed by Hoechst 33258 fluorescence
      staining. RESULTS: Each concentration of serum containning WEI KANG NING could
      inhibit cells proliferation. Among them, both high and medium concentration could
      inhibit longer. Moreover, high concentration could induce cells apoptosis.
      CONCLUSION: WEI KANG NING serum has anti-proliferation effect on MGC-803 cells
      and the effect may be related to cell apoptosis induced by WEI KANG NING.

PMID- 16981459
TI  - [Effects of Cinnabar and Realgar in Angong Niuhuang powder on heat shock protein,
      nitric oxide synthase and inflammatory cytokines in contusion cerebral edema].
AB  - OBJECTIVE: To explore the pharmacological mechanism of Cinnabar and Realgar in
      Angong Niuhuang powder (ANP). METHODS: SD rats were randomly divided into six
      groups (12 rats/group): normal controls group (NS group), contusion cerebral
      edema model group( CCE group) , cerebral edema rats administrated by cinnabar 0.
      15 g/kg 1h (CA group), cerebral edema rats administrated by realgar 0.15 g/kg 1h
      (RG group), cerebral edema rats administrated by Angong Niuhuang powder 1.5 g/kg
      1h (ANP I group), cerebral edema rats administrated by Angong Niuhuang powder
      substracted cinnabar and realgar 1.2 g/kg 1h (ANP II group). Each group was
      divided into two subgroups (6 rats/subgroup). The rats in subgroups were killed
      at 8h and 24h after modeling respectively. Expression of heat shock protein 70 (
      HSP 70) mRNA in brain tissues was measured by RT-PCR. Activities of nitric oxide
      synthase (NOS) and its isoenzymes (iNOS, cNOS) in brain tissues were tested by
      colorimetry. Levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1
      beta (IL-1beta) in serum were determined by radioimmunoassay (RIA). RESULTS:
      Expression of HSP 70 mRNA in ANP I group and ANP II group significantly increased
      as compared with CCE group 8h after being modeled (P < 0.05), and increase range
      in ANP I group were singificantly higher than that in ANP II group (P < 0.05).
      Activities of iNOS in CA group, RG group, ANP I group and ANP II group were lower
      than that in CCE group 8h after being modeled (P < 0.05) , and the activities in
      ANP I group were the lowest in the four groups. Levels of TNF-alpha in RG group,
      ANP I group and ANP II group decreased obviously as compared with CCE group 8h
      after being modeled (P < 0.05) , so did levels of IL-1beta in ANP I group and ANP
      II group (P < 0.05). But no significant difference was shown between ANP I group
      and ANP 11 group. CONCLUSION: HSP 70, iNOS, TNF-alpha and IL-1beta are involved
      in contusion cerebral edema. ANP and CA, RG in ANP are protective against CCE in
      rats. It may be associated with the increase of HSP 70 mRNA expression,
      inhibition of iNOS activity, and the decreasae of inflammatory cytokines (TNF
      alpha, IL-1beta) levels.

PMID- 16981460
TI  - [Experimental study on treatment of allergic asthma guinea pigs with different
      fractions of Modified Zhisousan].
AB  - OBJECTIVE: To study the effects of different fractions of Modified Zhisousan (MZ,
      MZC, MZS) on the contents of nitric oxide (NO), endothelin-1 (ET-1) and
      eosinophilia (EOS) in the allergic asthma guinea pigs and observe the pathology
      changes of lung tissue. METHODS: The number of EOS in the blood and
      bronchialveolar lavage fluid (BALF) was counted by Wright staining. The contents
      of ET-1 and No in serum and BALF were analyzed by RIA and nitric acid reductase
      method. The guinea pig lungs were observed under the optical and electron
      microscope. RESULTS: The number of EOS and the contents of ET-1 and NO in model
      group were higher than those in control group (P < 0.01). The pathological
      changes of lung were obvious. The number of EOS and the contents of ET-1 and NO
      were descended remarkably (P < 0.05 or P < 0.01) and the pathological changes in
      the lung tissue were lightened obviously in MZ and MZC groups, but MZS group had
      no such effects. CONCLUSION: MZC is the effective part of MZ and the anti
      asthmatic mechanisms ware related to its significant reduction in contents of ET
      1, NO, EOS and the damage of lung tissue possibly.

PMID- 16981461
TI  - [Research on resveratrol's mechanism of immunity in anti-aging].
AB  - OBJECTIVE: To research resveratrol's mechanism of immunity in anti-aging and
      explore the new clinical use of resveratrol. METHODS: The sub acute aging model
      was made by continuous subcutaneous injection of D galactose to mice inducing
      reactive oxygen species (ROS). Meanwhile, the resveratrol was given and its
      effect on anti-aging was observed. RESULTS: The resveratrol could increase the
      content of SOD and decrease the content of MDA in serum. There was no change in
      spleen index, but thymus index increased obvionsly. There was no change in the
      quantity of CD4+, but the quantity of CD8+ increased and the ratio of CD4+/CD8+
      was decreased. The serum IL-6 and IL-8 level were decreased obviously.
      CONCLUSION: The resveratrol possessed the function to anti-aging and the
      applications foreground in anyi-aging.

PMID- 16981462
TI  - [Comparative study on effects of rutin and quercetin on metabolism in osteoblast
      cells].
AB  - OBJECTIVE: To investigate the mechanism of rutin and its aglycone (quercetin) in
      preventing and treating osteoporosis and their effects on stimulating bone
      formation were studied comparatively in osteoblast cells. METHODS: The effects of
      rutin and quercetin on the proliferation, differentiation and mineralization were
      studied respectively by using tetrazolium (MTT), alkaline phosphatase (ALP) and
      mineralized nodules assays in newborn rat calvarial osteoblast (ROB) cells.
      RESULTS: Quercetin showed significant stimulatory effects on proliferation and
      mineralization in ROB cells, so it could promote bone formation. However, rutin
      could not imporve stimulation of bone formation because it increased
      proliferation and inhibited differentation and had no remarkable influence on ROB
      cells in vitro. CONCLUSION: Rutin showed less activity than quercetin on bone
      formation in ROB cells in vitro. Therefore the mechanism that some foods and
      traditional Chinese medicine containing rutin can prevent and treat osteoporosis
      is that its metaboite in vivo can promote bone formation in ROB cells.

PMID- 16981463
TI  - [Making of compound Rhizoma Acori Tatarinowii naphtha emulsion].
AB  - OBJECTIVE: To determine an ideal recipe and technique for making of compound
      Rhizoma Acori Tatarinowii naphtha emulsion (CRATNE) , diameter for the granule in
      10 to approximately 20 microm. METHODS: CRATNE was made by two-step
      emulsification and the recipe was evaluated to investigate the effect of diameter
      for the granule on stir time and stir speed and oxygen ventilated. RESULTS: The
      percentages of diameter for the granule in 10 to approximately 20 microm was 72%.
      Emulsion was made on recipe No. 4 [ Rhizoma Acori Tatarimowii naphtha (ml):
      liquid paraffin (ml): Sorbian monooleate (g): 0.5% gelatin solution (ml):
      distilled water (ml) is 1.05: 16: 7: 1: 16] and compound emulsion is made on
      recipe No. 4 [fore emulsion (g): Tween-80 (g): distilled water (ml) is 10: 1: 9].
      Recipe No. 4 was the best one if stiring at low speed through magnetic force
      mixer was used. Stir time was 1 min. The oxygen was ventilated with a flow rate
      of 2 L/min for CRATNE. Ventilation time was 1 h. The percentages of diameter for
      the granule in 10 to approximately 12 microm increased from 72% to 79%. was type
      W/O/W. CONCLUSION: The diameter of CRATNE for the granule is in 10 to
      approximately 20 microm, can be made following above-mentioned methods.

PMID- 16981464
TI  - [Study on extraction methods of activity components from Podophyllum emodi wall].
AB  - Supercritical fluid Extraction (SFE) with subsequent HPLC analysis was utilized
      to extract activity components such as podophyllotoxin, deoxypodophyllotoxin,
      kaempferol and quercetin from the roots and stems of Podophyllum emodi Wall. The
      extraction yields obtained by SFE were compared to those obtained by organic
      solvent extraction and were found to be comparable or lower. In addition, we used
      the orthogonal experiment which conducts with 3 factors and 4 levers in order to
      find the best dynamic extraction conditions.

PMID- 16981465
TI  - [The prenatal diagnosis and early intervention of nonsyndromic hearing loss of
      connexin26 gene].
AB  - OBJECTIVE: To detect the mutations of gene connexin26 in the pedigrees of
      nonsyndromic hearing loss, and to make prenatal diagnosis and carry out early
      intervention to the pedigrees with mutations of gene con nexin26. METHOD: The
      connexin26 gene of probands in 100 nonsyndromic hearing loss pedigrees was
      inspected by polymerase chain reaction, single strand conformational polymorphism
      and direct sequencing to detect the gene mutations. To the pregnant women in
      pedigrees with confirmed nosogenetic mutations of connexin26 gene, the prenatal
      diagnosis to the fetus by cordocentesis was made and the early intervention was
      carried out. RESULT: The homozygous deletion C at position 233-235 of connexin26
      cDNA was proved to be a nosogenetic mutation, and G79A, G109A, A341G, G442A,
      G506A and T608C were proved to be polymorphisms. In the prenatal diagnosis for
      the second pregnancy of a woman in a pedigree with the homozygous deletion C at
      position 233-235 of connexin26 cDNA, the same mutation in the fetus' connexin26
      gene was found and she was advised to end the pregnancy. CONCLUSION: The
      homozygous deletion C at position 233-235 of connexin26 cDNA will induce
      autosomal recessive nonsyndromic hereditary hearing loss and the heterogeneous
      mutation will not cause hearing loss. The prenatal diagnosis and early
      intervention can prevent the birth of deaf children. This is the first time in
      our country to make prenatal diagnosis and proceed early intervention to the
      fetus of hereditary hearing loss.

PMID- 16981466
TI  - [Treacher Collins syndrome: case report and literature review].
AB  - OBJECTIVE: To study the genetic background, clinical features, diagnosis,
      management, and prenatal testing and counseling of Treacher Collins syndrome
      (TCS). METHOD: The clinical data of a patient and his mother suffering from TCS
      was reported and the relevant literatures were also reviewed. RESULT: TCS is an
      autosomal dominant disorder characterized by craniofacial mal-development,
      including antimongoloid slant of the eyes, micrognathia, microtia and other
      deformity of the ears. TCS results from the mutation in TCOF1 gene (Treacher
      Collins-Franceschetti Syndrome gene), located in 5q32-q33.1. Diagnosis of TCS is
      made through clinical evaluation, radiographic examination, and molecular genetic
      analysis. Treatment is tailored to the specific needs of each individual by a
      multidisciplinary craniofacial management team. The choosing of optimal operation
      time and method is very important. Prenatal testing and genetic counseling for
      risky pregnancy is necessary. CONCLUSION: The stepwise regimen of treatment is
      craniofacial reconstruction, orthognathic procedures, orthodontic alignment of
      the teeth, nasal reconstruction, external ear reconstruction and external
      auditory canal and middle ear reconstruction.

PMID- 16981467
TI  - [Self hearing recovery in infants with hearing loss after universal newborn
      hearing screening system].
AB  - OBJECTIVE: To analyze the reasons of hearing recovery of newborns and infants
      which were diagnosed hearing loss within 3 months old by universal newborn
      hearing screening (UNHS) system. METHOD: Newborns and infants born from Nov. 2001
      to Jun. 2005 in Shanghai who failed UNHS were studied. Audiometric evaluations
      were performed in Shanghai Children's Hearing and Speech Center. Those with
      hearing loss were diagnosed within 3 months old and were followed-up at least 6
      months. Analysis was carried out targeting for hearing recovery cases. RESULT:
      Six hundred and eighty-one cases failed the UNHS and were confirmed hearing loss
      within 3 months old. During the 6-24 months period of followed-up, 94 (13.8%) of
      681 infants caught normal hearing. Among these 94 infants(115 ears), otitis media
      with effusion was found in 56 cases (59.6%), no reasonable cause was found in the
      other 38 cases (40.4%). Among the 115 ears which recovered to normal, there were
      105 ears (91.3%) with primary diagnosis of mild hearing loss, 8 ears (7.0%) with
      moderate hearing loss and 2 ears (1.7%) with moderate-severe hearing loss. No
      recovery was found in the cases with primary diagnosis of severe and profound
      hearing loss. CONCLUSION: Newborns and infants with hearing loss diagnosed within
      3 months old have possibility to recover as they are growing. The critical
      reasons might be self-recovery from otitis media with effusion and outcomes of
      central auditory system development.

PMID- 16981468
TI  - [Analysis of the related factors that influence the effect of hearing aid].
AB  - OBJECTIVE: To investigate the related factors that may influence the effect
      hearing aid for sensorineural hearing loss patients. METHOD: Sixty cases with
      moderate to severe sensorineural hearing loss were selected. Audiological
      measurements were performed before and after hearing aiding. Factor analysis was
      carried out. RESULT: The unaided hearing level (UHL), Speech perception thresher
      (SPT), speech recognition thresher (SRT), speech recognition score (SRS) and
      aided hearing level (AHL) have notable influence on the effect of hearing aid
      fitting. The most comfortable level (MCL), age, education period, hearing loss
      duration and aided duration also have some influence on the results. CONCLUSION:
      Hearing aid is not only a hearing compensating tool, it also has some therapeutic
      effect as well.

PMID- 16981469
TI  - [Equivalence analysis of disyllabic Mandarin speech test materials].
AB  - OBJECTIVE: To evaluate the equivalence of difficulty of disyllabic Mandarin
      Speech Test Materials (MSTM) in order to facilitate wider use of speech
      audiometry in Chinese audiology clinics. METHOD: The Mandarin disyllabic
      materials, including 10 lists with 50 words in each, have been recorded and
      converted digitally into CD format. Sixty-five subjects (the age-range 18-25
      years) with normal hearing who speak Mandarin well in their daily lives
      participated in this study. Five of them joined the pilot study, which aimed to
      identify a presentation level which would be used into the formal test. The other
      sixty subjects participated in the formal speech perception test. The results
      were analyzed statistically with Statistical Package for the Social Sciences
      Software Version 11.0 (SPSS 11.0). RESULT: Nine of the 10 lists were found to
      have equal difficulty with application of the ANOVA and SNK-Q statistical
      methods. CONCLUSION: Nine lists of 50 words of these Mandarin disyllabic
      materials can be considered to have equal difficulty and could be used in a
      clinical setting.

PMID- 16981470
TI  - [ABR and CNAP combined monitoring during the lateral skull base surgeries].
AB  - OBJECTIVE: Through the application of ABRs and CNAPs monitoring during the
      lateral skull base surgeries, we intended to detect the causes of intraoperative
      hearing damage and estimate the value of the techniques. METHOD: Intraoperative
      auditory monitoring were performed in 14 lateral skull base surgeries in which
      hearing preservation were attempted. ABRs was recorded in all the steps of the
      procedure, while CNAPs was recorded after opening the dura. All patients' hearing
      levels were followed up. RESULT: All the patients had auditory evoked potentials
      (AEPs) change during the procedure, especially after the step of drilling
      [prolonged (0.26 +/- 0.19) ms] and during the encephalic manipulations [prolonged
      (0.68 +/- 0.38) ms]. Some patients' AEPs recruited in the end of procedure.
      CONCLUSION: The intraoperative auditory monitoring could play a role in
      preventing the hearing damage in the procedure. Drilling may cause the hearing
      damage. After relieving the manipulation inducement, the hearing damage would
      partially recruit. The prognosis of hearing is related to the prolongation of
      wave latencies in the procedure. A combination use of the ABR and CNAPs may be a
      better method of intraoperative auditory monitoring.

PMID- 16981471
TI  - [The application of 3D reconstruction of CT scans for the observation of the
      cochlear implanted electrode location].
AB  - OBJECTIVE: To discuss the different methods of computed tomography (CT) scans and
      three dimensional reconstruction of inner ear with implanted electrodes, and to
      evaluate the value and image features of these methods. METHOD: Six cochlear
      implant (MEDEL Combi 40+, Advanced Bionics) recipients were involved in this
      study. The implanted electrodes of all patients were examined on the seventh
      postoperative day. The data of the CT scans was transferred to workstation for
      three dimensional reconstruction by volume rendering (VR), average intensity
      projection (AIP) and surface shaded display (SSD). RESULT: The three methods of
      three dimensional reconstruction provided satisfactory image of implanted
      electrode including the shape and the special relationship of the electrode in
      the inner ear. The insertion depth of the electrode can be evaluated directly.
      Moreover, each of the electrode pairs can be identified clearly. CONCLUSION:
      Postoperative evaluation of the implanted electrode with three methods of CT
      scans with three dimensions reconstruction of inner ear provide more accurate
      image of the special relationship of the electrode in the cochlear canal with
      direct demonstration of electrode insertion depth in the cochlea.

PMID- 16981472
TI  - [Effect of nitric oxide and nitric oxide synthase on sensorineural hearing loss
      secondary to secretory otitis media].
AB  - OBJECTIVE: To evaluate the effect of nitric oxide synthase (NOS) and nitric
      oxide(NO) on sensorineural hearing loss (SNHL) secondary to secretory otitis
      media (SOM). METHOD: Samples of middle ear effusion were collected at the time of
      tympanocentesis from 16 cases of SOM with SNHL(group A) and 16 cases of SOM
      without SNHL(group B). And the concentration of NO and NOS activity in middle ear
      effusion were detected by colorimetric assay (Griess method). RESULT: The
      concentration of NO in group A (181.19 +/- 44.31) micromol/L was significantly
      higher than that in group B (137.00 +/- 40.67) micromol/L (P < 0.01). The NOS
      activity in group A (97.69 +/- 29.62)U was also significantly higher than that in
      group B (75.50 +/- 26.99)U (P < 0.05). CONCLUSION: Excess generation of NO in
      middle ear effusion which synthesized by NOS may hurt inner ear directly by its
      cytotoxic action or enhance local inflammatory reaction with other inflammatory
      factors. This study suggests that NO play a significant role in the process and
      pathogenesis of SNHL secondary to SOM.

PMID- 16981473
TI  - [Clinical study of acute low-tone sensorineural hearing loss].
AB  - OBJECTIVE: To study the etiology, diagnosis and therapeutic strategies of acute
      low-tone sensorineural hearing loss (ALHL). METHOD: Fifty-five patients (58 ears)
      with ALHL were selected for this study. With detailed history collection,
      otological examination and pure tone audiometry,acoustic immittance and auditory
      brainstem response (ABR), all cases were divided into two groups, the prednisone
      group and the control group, randomly with six months follow-up. RESULT: ALHL
      mainly affected young people. The symptoms included the sensation of ear
      fullness, low-tone tinnitus, and hearing impairment. Otological examinations
      showed normal results. Mild to moderate sensorineural hearing loss at low
      frequencies and type "A" tympanograms were found in all cases. Acoustic stapedial
      reflexes were elicited in 49 out of 58 affected ears and 40 of them had positive
      results on the Metz test. ABR responses were normal in all 45 tested ears. with
      comparison of the two groups, the effect of prednisone group was superior to that
      of the control group. CONCLUSION: ALHL patients are clinically characterized by
      low-tone tinnitus, aural fullness and hearing loss, which mainly involve
      unilateral ear. Audiological findings indicate cochlear impairment, which only
      invades low frequency region. This study suggest that the corticosteroid therapy
      probably have some effect.

PMID- 16981474
TI  - [Sinus histiocytosis with massive lymphadenopathy].
AB  - OBJECTIVE: To explore the therapeutic strategy of sinus histiocytosis with
      massive lymphadenopathy (SHML). METHOD: The six patients with SHML were treated
      with different therapeutic strategies. RESULT: Two of six patients were treated
      with radiation therapy and chemical therapy resulting in tumor lessened markedly.
      The tumor of other four cases disappeared after comprehensive treatment including
      operation, immunity and interferon therapy. CONCLUSION: The comprehensive
      therapy, mainly including surgical treatment, is effective for SHML.

PMID- 16981475
TI  - [Thyroid malignant tumor with flare up glottic paralysis for first symptom].
AB  - OBJECTIVE: To approach clinical feature of thyroid malignant tumor with Flare up
      glottic paralysis for first symptom, and analysis that should be avoided missed
      diagnosis and misdiagnosis during diagnosis and treatment. METHOD: Retrospective
      research five cases of thyroid malignant tumor with flare up glottic paralysis
      papillary adenocarcinoma of thyroid by pathology. Four cases had one side glottic
      paralysis, the same side thyroid were moved after dissecting the recurrent
      laryngeal nerve. Three cases of them recovered normal vocal cord function, the
      function of one case was compensated by another side vocal cord. The last one had
      right gliotic paralysis first, then both cricoarytenoid joint had been fixed,
      hoarse voice was worse and developed to dyspnea since the tumor invaded in larynx
      one year later. We only did cut the right thyroid and right half larynx, but the
      tumor came back again in larynx in three months, then had to removal whole larynx
      without recurrence follow up two years. CONCLUSION: For the flare up glottic
      paralysis with same side tiny thyroid tumor, we suggest that the thyroid must be
      made operation research if no other reasons, dissecting and protecting the
      recurrent laryngeal nerve during operation, and cut reasonable thyroid and others
      according to fast pathologic diagnosis.

PMID- 16981476
TI  - [Excitotoxic effects of glutamate on the in vitro spiral ganglion cells].
AB  - OBJECTIVE: To explore the excitotoxic effects of glutamate on the in vitro
      primarily cultured spiral ganglion cell (SGC) of rat. METHOD: Spiral ganglion
      cells (SGCs) were cultured in vitro for 4 days, and exposed to 1 mmol/L glutamate
      for 24 hours. Damaged cells double-labeling with Hoechest33258 and PI were
      observed by fluorescence microscope. Ffluo-3 and CLSM for measurement of
      intracellular calcium levels were also utilized. RESULT: Most cells were damaged
      and the intracellular calcium increased and after exposure to 1 mmol/L glutamate
      (P < 0.05). CONCLUSION: Glutamate excitotoxicity was associated with free
      intracellular calcium ion concentration elevation in SGC.

PMID- 16981477
TI  - Lawsuit over lack of call coverage raises new concerns about liability.
AB  - Regarding poor call coverage, take every step possible to minimize your potential
      exposure to litigation. Here are some strategies: Have policies and procedures
      for addressing the needs of patients for times when coverage is not available.
      Make sure potential patients and families are clear on the services your ED does
      and does not offer. Be sure to have transfer relationships set up with facilities
      that provide the services your ED cannot.

PMID- 16981478
TI  - Is OPPS rule as good as it looks for EDs?
AB  - The proposed payment rule for hospital outpatient services could significantly
      enhance your department's revenues in the coming year. Familiarizing yourself
      with the new service levels can help point out strategies that will help boost
      your Medicare reimbursement. The new Level 5 ambulatory payment classification
      (APC) will pay nearly 100 dollars more than this year's highest level, so
      determine the percentage of your patients that fall within that category to
      estimate your potential reimbursement gains. Offer fast track services or place
      physicians in triage to reduce the number of low-acuity patients that come into
      your ED. Market appropriate use of your ED to limit the number of patients who
      come to your department seeking primary care services.

PMID- 16981479
TI  - EKG at triage slashes door-to-aspirin time.
AB  - Giving all chest pain patients an electrocardiogram (EKG) in triage can
      significantly improve treatment times and quality of care and it eliminates the
      need to prioritize patients and takes undue pressure off the nurses, ED managers
      say. Triage delays in chest pain evaluation are eliminated by giving all patients
      the same treatment. Time to first aspirin at one hospital was slashed from 67
      minutes to eight minutes. Asking nurses to differentiate patients on the basis of
      an interview and a set of vitals is unrealistic, managers say.

PMID- 16981480
TI  - Positive feedback spurs process improvements.
AB  - Motivate your staff to strive for excellence by clearly establishing optimal
      standards of care and then rewarding and recognizing your top performers.
      Identify "excellence", using standards such as core measures from the Centers for
      Medicare & Medicaid Services. Post pathways on the department bulletin board to
      make sure all your staff members are aware of what they are striving for. Reward
      those who achieve excellence with creative gifts, and publicly recognize them
      within the department.

PMID- 16981481
TI  - Increasing ICU bed capacity cuts diversions.
AB  - A new study demonstrates a real dollar cost to diversions, which can give ED
      managers added ammunition when lobbying administration for increased bed capacity
      hospitalwide. Here are some strategies you can use: Point out the demonstrated
      link between increased bed capacity in the intensive care unit and reduced
      diversions. Emphasize the fact that when patients are boarded, staff morale is
      negatively affected. Because your ED may represent 30% of your hospital's volume,
      note the connection between improved flow and patient satisfaction.

PMID- 16981482
TI  - Applying EMTALA to behavioral emergencies.

PMID- 16981483
TI  - Adult obesity.
AB  - OBJECTIVES: Based on direct measures of height and weight, this article compares
      the prevalence of obesity among adults aged 18 or older in 1978/79 and 2004.
      Prevalence by demographic, socio-economic and lifestyle characteristics is
      presented, along with associations between obesity and selected chronic
      conditions. Canadian and US data are also compared. DATA SOURCES: Data are from
      the 2004 Canadian Community Health Survey: Nutrition, the 1978/79 Canada Health
      Survey and the 1986 to 1992 Canadian Heart Health Surveys. US data are from the
      1999-2002 National Health and Nutrition Examination Survey. ANALYTICAL
      TECHNIQUES: Descriptive statistics were used to estimate the proportion of adults
      who were obese in 2004 in relation to selected characteristics. Logistic
      regression models were used to examine relationships between obesity and high
      blood pressure, diabetes and heart disease, controlling for socio-economic status
      and other risk factors such as smoking and physical activity. MAIN RESULTS: In
      2004, 23% of adults, 5.5 million people aged 18 or older, were obese--up
      substantially from 14% in 1978/79. An additional 36% (8.6 million) were
      overweight. Obese individuals tended to have sedentary leisure-time pursuits and
      to consume fruit and vegetables infrequently. As body mass index (BMI) increased,
      so did an individual's likelihood of reporting high blood pressure, diabetes and
      heart disease.

PMID- 16981484
TI  - Overweight and obesity among children and youth.
AB  - OBJECTIVES: This article describes the prevalence of overweight and obesity among
      Canadian children and youth aged 2 to 17, based on direct measurements of their
      height and weight. Data from 1978/79 and 2004 are compared, and trends by sex and
      age groups are presented. DATA SOURCES: Data based on direct measurements are
      from the 2004 Canadian Community Health Survey (CCHS): Nutrition. Other
      information is from the 1978/79 Canada Health Survey and the 1999-2002 National
      Health and Nutrition Examination Survey, conducted in the US. ANALYTICAL
      TECHNIQUES: The estimated prevalence of overweight and of obesity, including an
      overall rate reflecting both, was based on 2004 CCHS data for 8,661 children and
      youth whose height and weight were measured. MAIN RESULTS: In 2004, 26% of
      Canadian children and adolescents aged 2 to 17 were overweight or obese, and 8%
      were obese. Over the past 25 years, the prevalence of overweight and obesity
      combined has more than doubled among youth aged 12 to 17, while the prevalence of
      obesity alone has tripled. Children and youth who ate fruit and vegetables at
      least five times a day were substantially less likely to be overweight or obese
      than were those who ate these foods less often. The likelihood of being
      overweight/obese rose as "screen time" (watching TV, playing video games or using
      a computer) increased.

PMID- 16981485
TI  - Obesity--a growing issue.
AB  - OBJECTIVES: This article, based on longitudinal data, follows a sample of people
      who were aged 20 to 56 in 1994/95 to determine the percentage who made the
      transition from normal to overweight, or from overweight to obese by 2002/03.
      Characteristics that increased the chances of overweight people becoming obese
      are examined. DATA SOURCES: The data are from five cycles of the National
      Population Health Survey, 1994/95 through 2002/03. ANALYTICAL TECHNIQUES: Cox
      proportional hazards modelling was used to identify variables associated with an
      increased or decreased risk of becoming obese; 1,937 men and 1,184 women who were
      overweight in 1994/95 were selected. MAIN RESULTS: Close to a third (32%) of
      people who were aged 20 to 56 and of normal weight in 1994/95 had become
      overweight by 2002/03. During the same period, almost a quarter of those who had
      been overweight in 1994/95 had become obese. Among people who were overweight,
      the risk of obesity was relatively high for younger men and members of low-income
      households. Overweight men who smoked or who had activity restrictions had a high
      risk of obesity. Physical activity helped women avoid obesity.

PMID- 16981486
TI  - Trends in adult obesity.

PMID- 16981487
TI  - Regional differences in obesity.

PMID- 16981488
TI  - Treatment of patients with substance use disorders, second edition. American
      Psychiatic Association.

PMID- 16981489
TI  - [Incidence of avian flu worldwide and in the Russian Federation. Improvement of
      surveillance and control of influenza during preparation for potential pandemic].
AB  - Problem of influenza and acute respiratory virus infections (ARVI) remains one of
      the most urgent medical and socio-economic issues in despite of certain
      achievements in vaccine and chemoprophylaxis. In Russia influenza and ARVI
      account for up to 90% of the total annual incidence of infectious disease (up to
      30 million of sick people; 45-60% of them are children). Economic damage, caused
      by influenza and ARVI, makes around 86% of total economic damage, caused by
      infectious diseases. WHO predicts that in the years coming a new antigenic
      influenza virus will appear, which can lead to development of large pandemia with
      4-5 times increase in disease incidence and 5-10 times increase in death rate.
      During 2005 some changes in animal influenza epidemiology were registered. New
      cases of people infections are detected, the virus has spread to some new
      countries. Avian influenza is a high contagious virus infection that can affect
      all bird species. For birds influenza is enteral infection, it severely affects
      parenchymatous organs, especially spleen, and lungs. By now it is known that
      carriers of avian influenza virus H5N1 can be all known species of wild waterfowl
      and near-water birds. Poultry is highly susceptible to many stocks of influenza
      virus H5N1, death rate reaches 100%. At that hens, especially chickens, are most
      susceptible. From January 2004 to 24th November 2005 in the world there were
      detected 131 cases of influenza, caused by virus A/H5N1/, 68 of them (51%) ended
      in lethal outcome (Vietnam--92 cases, Thailand--21 cases, Cambodia--4, Indonesia-
      11, China--3). Most of the described cases of avian influenza resulted from
      direct contact with infected birds (handling bird internal organs is especially
      dangerous). In frozen meat of infected birds the virus can remain for about one
      year. Heating kills virus (no cases of infection caused by use for food of
      poultry products were detected). In order to prevent wide ranging spread of
      infection over Russia it is necessary to organize medical monitoring of sea
      ships, aircraft and train crews, arriving from the countries where influenza H5N1
      cases were detected, in case of need to arrange raids to outlets and markets to
      detect poultry and poultry products brought from these countries. In Russia it is
      necessary to prepare a reserve of vaccine strains of viruses--potential causative
      agent of pandemic, including H5N1 and H7N7, that can start to vaccine
      reproduction immediately in case of pandemic.

PMID- 16981490
TI  - [Avian flu epizootia and its prevention].
AB  - In the review cited the data about avian flu epizootia for last years, about
      economic damage by epizootia, the information on an infection of people by
      viruses of animals. Problems the development of vaccines against a avian flu,
      including ways of designing of vaccine strains are discussed. Data on methods of
      struggle with avian influenza epizootia of poultry, about methods of prevention
      the epizootia and uses for this purpose of vaccines and drugs are resulted.

PMID- 16981491
TI  - [Development of the anti-influenza H5N1 vaccines worldwide and in Russia].
AB  - Article is dedicated to analytical investigation of the problem of current
      technologies in construction and manufacturing of anti-influenza vaccines.
      Epidemiological events in July-November 2005 in Russia (mainly in Siberia) and
      later in Ukraine showed that Health Care system was not ready for that turn over
      of epidemiological situation. It was completely the same situation in other
      countries. There are two general questions of a readiness in pre-pandemic
      situation: level of a diagnostic monitoring of epidemiological situation and
      preparedness to fast production of actual vaccine preparations. First task can be
      solved by immediate production of diagnostic sets for regional branches of
      National WHO Centers, and a second one depends on application of a novel
      approaches in construction of a anti-influenza vaccines. The construction of anti
      influenza vaccines is based on genetic engineering (reverse genetics) and
      manipulation with plasmids carried out basic viral genes. Reassortation
      technology for preparation of hybrid viruses is going to the past by objective
      reasons. Advanced technologies are safety in laboratories and in manufacturing
      facilities. Moreover, genetic engineering in this field allows to planing the
      construction of vaccines bank, when the prognoses for actual viruses include more
      then two strains with different antigenic properties.

PMID- 16981492
TI  - [Comparison of in vitro and in vivo methods of evaluation of the efficacy of
      influenza virus hemagglutinin inhibitors].
AB  - One of the problem in the selection of the most effective antiviral preparations
      with a broad spectrum of antiviral protective activity, is the "continuity" of
      assays of different level of complexity so, that the most effective antiviral
      therapeutic, selected by in vitro assays would be the most effective in vivo.
      Comparative study of the efficacy of the influenza virus inhibitor in the assays
      of inhibition of virus binding with fetuin, inhibition of infectious focus
      forming units in MDCK cells, inhibition of virus yield in infected MDCK cells,
      and inhibition of influenza virus infectivity in mice infected by viral aerosol
      are presented. The value of 50% inhibiting concentration IC50 for the pare
      "influenza virus strain A/NIB/23/89-MA-inhibitor tetra-Aca6-6'SLN" corresponded
      to 6-10 microM and was invariant for three different tests--in vitro assay of
      inhibition of virus binding with fetuin, inhibition of yield in infected MDCK
      cell culture, and inhibition of virus infectivity in mice, but not for the assay
      of inhibition of infectious focus forming units in cell culture.

PMID- 16981494
TI  - [Results of two-year-old inspection of the presence of infuenza virus in wild
      birds in Western Mongolia].
AB  - The results of virology inspection of the wild birds living in territory of the
      Western Mongolia, carried out in 2003-2004 are presented. For the specified
      period influenza viruses H3 and H4 subtype hemagglutinins are isolated from
      birds. It is revealed taxonomic and ecological heterogeneity of the birds
      involved in maintenance of circulation of influenza viruses in the given
      territory. Influenza viruses are isolated from birds of 5 special groups; among
      them there are preferring water and nearwater biotops, a species preferring dry
      plain region, and also a species which habitat does not depend from water's
      territories.

PMID- 16981493
TI  - [Study of highly pathogenic H5N1 influenza virus isolated from sick and dead
      birds in Western Siberia].
AB  - The mass destruction of domestic birds has been registered in July, 2005 in
      Novosibirsk region. Influenza virus H5N1 have been isolated from bodies of the
      lost birds on developing chicken embryos and identified by serological and
      molecular biological methods. M-gene and genes coding hemagglutinin and
      neurominidase were in part sequening. The phylogenetic analysis of hemagglutinin
      gene has shown, that the isolated viruses are forming a claster with strains,
      isolated from birds during outbreak of the bird's flu on lake Tsinghai (Qinghai)
      in China in 2005, in Japan in 2004, and also with H5N1 strains, isolated from the
      person and birds in the countries of Southeast Asia during ipizootia in 2003
      2004. The site of the restriction which associated with pathogenicity of isolated
      avian influenza viruses H5 serogroup, corresponds to sequence of high pathogenic
      strains, circulating in the countries of Southeast Asia. The test for
      pathogenicity with use of chickens has confirmed, that researched strains were
      high pathogenic for birds.

PMID- 16981495
TI  - [Circulation of type A influenza viruses in poultry during the pre-epizootic
      period of 2005 in Novosibirsk region].
AB  - Work is devoted to studying of circulation of avian flu influenza A (H5N1) virus
      at poultry in territory of Novosibirsk region in preepizootic period. 1901 sample
      from clinically healthy poultry is collected and investigated. On chicken embryos
      it has been isolated 28 virions, including from poultry of the industrial
      maintenance--16, from the poultry contained in private farmsteads--12. At the
      analysis of isolates it has been shown, that among poultry in preepizootic period
      circulated various serovars of influenza viruses namely, HI, H4 and H3
      serogroups. The percent of isolates from geese of the industrial maintenance
      increased to 0.6% depending on area. The percent of isolates from a bird
      contained in private farmsteads, increased to 7.5%. The greatest percent of
      isolates was observed from the samples taken from hens--77. Thus, it is shown,
      that among poultry circulation of not pathogenic influenza viruses of type A is
      the usual phenomenon, and asymptomatic carriers 7.5% of a livestock. Also it has
      been established, that in preepizootic period 2005 (January-June) at poultry it
      is not revealed influenza viruses of H5 serotype, caused epizootia at Summer of
      2005 in territory of Western Siberia.

PMID- 16981496
TI  - [Epizootic and epidemiological situation with the avian flu in Dovolensk and
      Kupinsk areas of Novosibirsk region and the preventive measures].
AB  - Results of the analysis registered avian flu epizootia are submitted. Diseases
      were registered as among wild birds, and poultry. From a biological material from
      a poultry and wild bird of some villages of Novosibirsk region the influenza
      virus type A (H5N1) is allocated. Carrying out sanitary and antiepidemic measures
      is organized. It is established, that disease and a mass destruction of poultry
      have taken place after contact to a wild bird on lakes. It is revealed, that the
      degree of distribution of a mass destruction of poultry on farmsteads in the
      struck territories depends on terms of carrying out of necessary measures on
      localization of the foci. Occurrence of new cases of disease among wild birds and
      poultry in 2006 as lakes in this territory are a place of nesting of the wild
      birds being the reservoir of the influenza virus is predicted.

PMID- 16981497
TI  - [Organization of antiepidemic and antiepizootic measures during liquidation of
      the mass losses of poultry from from avian flu in Novosibirsk region].
AB  - The data on preparation of the basic documents regulating work in conditions of
      an extreme situation--registration of a mass destruction of poultry in personal
      farmsteads of citizens in Novosibirsk region are submitted. Circuits of the daily
      reporting on a case, on household detours, under actions of depopulation of
      poultry have been developed. Cited concrete works given on the periods, the order
      of decision-making, action of special structures and results of work for the
      period of avian flu epizootia.

PMID- 16981498
TI  - [Operational experience of disinfection service of Novosibirsk region with
      liquidation of the avian flu foci in Kupinsky, Zdvinsky and Dovolensky regions in
      August, 2005].
AB  - Results of work of disinfection service using a complex of disinfecion's measures
      on a mode against virus infections are resulted. In view of absence now
      methodical normative documents on modes of disinfection in the centers of the
      bird's flu the recommendations on use of new disinfectants are made.

PMID- 16981499
TI  - [Operational experience with liquidation of avian flu foci in Zdvinsk of
      Novosibirsk region].
AB  - The operational experience on liquidation of the centers of the avian flu in
      separate region of Novosibirsk is considered. From 32 settlements in 7 (22%) have
      been registered the centers of a case of a bird. Despite of undertaken measures
      under the prevention of distribution of an infection and occurrence of the new
      centers, during first time the case of a bird proceeded because of proceeding
      free ride out of poultry on lakes. Carrying out quarantine and actions on mass
      depopulation of birds appeared effectual measures on liquidation of the foci.
      Taking into account features of this area (a plenty of lakes) with nesting a wild
      waterfowl and accepted free ride out for poultry, the conclusion about an
      opportunity of occurrence and development new epizootia of bird's flu is made
      during spring-autumn of 2006.

PMID- 16981500
TI  - [Detection of RNA and specific antibodies against influenza virus A (H5N1) in
      human samples].
AB  - Results of inspection 451 persons in the age of from 19 till 58 years and 2
      children in the age of till 2 years on presence of specific antibodies and RNA of
      the infuenza virus A (H5N1) are submitted. RNA of infuenza virus A (H5N1) in
      researched samples is not revealed. Specific antibodies to a infuenza virus A
      (H5N1) in a blood serum of 211 patients and donors it is not revealed.

PMID- 16981501
TI  - [The organization, control and coordination of measures for localization and
      liquidation of mass poultry loss and prevention of human diseases caused by avian
      flu in Ordynsk area of Novosibirsk region].
AB  - Materials on the organization, the control and to coordination of actions of
      services in carrying out of actions on localization and liquidation of the
      centers of a mass destruction of birds and preventive measures of people diseases
      by avian flu during the period from July, 21 till September, 18, 2005 are
      submitted. The basic actions which have been carried out by a territorial
      department, the quarantine of poultry excluding contact with wild birds,
      depopulation of a sick and suspicious birds on disease and disinfection in the
      foci of a mass case, including installation disinfection barriers, etc. As a
      result of spent actions the bird's mass destruction has been stopped, quarantine
      is taken off 10.11.2005. The conclusion is made, that due to carrying out
      sanitary-preventive and antiepidemic measures it is possible not only to locate,
      but also completely to liquidate a mass destruction of birds.

PMID- 16981502
TI  - [Epizootia of the avian flu among the wild waterfowl in Sargatsk of Omsk region
      in 2005].
AB  - The epidemiological characteristic of avian flu among a wild waterfowl in
      Sargatsk region in 2005 is presented. The analysis of the climate-geographical
      characteristic of region and the data on migration and specific structure of a
      wild waterfowl, and also results of investigation of the facts of its destruction
      are submitted. Laboratory research with the PCR help has confirmed presence of
      influenza virus A (H5N1) at a wild birds. As a result of carried out in the
      period of epizootia in full preventive and antiepidemic measures, including
      quarantine contacts resulted in absence between a wild birds and poultry, with
      out of raid to the maintenance of poultry on farm-steads, etc., the mass
      destruction of poultry was absent. It is marked, that with a view of maintenance
      of epidemiological well-being in region high readiness for actions in conditions
      of an extreme situation, and also vaccination of the population should be kept.

PMID- 16981503
TI  - [Organization of sanitary and epidemiological measures to protect the Omsk region
      involved in epizootia of avian flu].
AB  - In article organizational aspects of carrying out preventive and antiepidemic
      actions at a regional level are considered at the bird's flu epizootia. Epizootic
      researches have shown, that infection of poultry has taken place as a result of
      contact to a wild bird. Serological inspection 521 persons on presence of
      antibodies to a influenza A (H5N1) has not revealed seropositive persons. The
      conclusion, that the forecast of development of a situation for spring of 2006 is
      made in view of a direction of migration of a wild waterfowl is unfavourable.

PMID- 16981504
TI  - [Surveillance measures at joint-stock company "Poultry Farm Lubinskaya" during
      the period of avian flu epizootia in Omsk region].
AB  - The organization of sanitary-and-epidemiologic supervision of an integrated
      poultry farm during epizootia of avian flu is devoted. The unsuccessful situation
      demands acceptance of additional measures which provided performance
      antiepizootic, preventive and antiepidemic measures with a view of restriction
      and distribution of an infection on poultry-farming enterprise. The disinfection
      barriers of several levels are established. Are organized a sanitary filtrates
      for the personnel and regular medical supervision over workers of the enterprise
      and their families. It is carried out the serological control over presence of
      specific antibodies to a virus of influenza virus among the workers contacting to
      a bird. Monitoring research of tests of blood of birds on antibodies to the
      influenza virus was carried out since August, 2005.

PMID- 16981505
TI  - [Epizootological and epidemiological features of the avian flu outbreak in the
      Chelyabinsk region in season 2005].
AB  - Results of the analysis of epizootological and epidemiological situations on
      avian flu in the Chelyabinsk region in season 2005 are submitted. Features of the
      foci of the avian flu in the given territory are marked. In particular, the
      struck settlements were marked by a plenty of nearby reservoirs. On all
      farmsteads perished on the average from 53% up to 68% of a bird contained at the
      moment of disease. Hens were mainly amazed. However in well isolated private
      enterprises the poultry remained healthy. The conclusion that the primary foci of
      the avian flu are connected to disease of wild birds which case was marked on
      reservoirs of this territory is made. The forecast for spring and autumn of 2006
      on disease the bird's flu remains adverse, presence of the infected territories
      kept since 2005 is possible. Feature epizootic process in 2006 can be a presence
      of a plenty of the young growth more subject to disease that can lead to increase
      in a level of disease the bird's flu.

PMID- 16981506
TI  - [Epizootic situation with the avian flu in Kurgan region].
AB  - The epizootia on avian flu and a measure on its liquidation are stated. The
      increase in number of a wild waterfowl in 2005 is marked in comparison with 2002.
      It is determined, that disease among poultry arose in the facilities which are
      taking place near of reservoirs at ride out of its contents. The complex of
      sanitary-and-hygienic measures are carried out with the purpose of the prevention
      of disease among people. Cases of disease caused by an avian influenza among
      people it is not revealed.

PMID- 16981507
TI  - [Avian flu in Altay territory].
AB  - The avian flu epizootia among wild waterfowl and poultry in personal farmsteads
      is described. In 38.9% of tests from a sectioning material from bird's mass
      destruction the genetic materials of a influenza virus type A (H5N1), and in 24%
      of tests of serum antibodies to a influenza virus type A (H5N1) in diagnostic
      titers are revealed. It is carried out serological monitoring among workers of
      integrated poultry farms and the population. Activation of epizootic process in
      second half of summer and is predicted by Autumn, 2006. For the prevention of
      distribution of disease among birds and infection of the person carrying out of a
      complex of the actions directed on creation of quarantine for a wild waterfowl
      and restriction of contacts to a poultry, and on vaccine prevention from annual
      100% immunization of workers of integrated poultry farms is necessary.

PMID- 16981508
TI  - [Some aspects of avian flu in the Tyumen region].
AB  - The list of the actions spent in the summer of 2005 in territory of the Tyumen
      region, in connection with a destruction of wild birds and poultry from the avian
      flu is submitted. Except for the quarantine and other sanitary-epidemic measures
      warning drift of a avian influenza virus in facilities, it is carried out of
      serological monitoring among workers of poultry-farming facilities and the
      population of the struck settlements on presence of antibodies to an influenza A
      (H5N1) virus. Taking into account ways of migration of a wild waterfowl in this
      territory, probability of contact to it and risk of infection of people, the
      conclusion about necessity of continuation the monitoring behind circulation of
      an avian influenza virus in region is made.

PMID- 16981509
TI  - Diving into the gene pool.

PMID- 16981510
TI  - How to spot a liar.

PMID- 16981511
TI  - The sports-drink wars.

PMID- 16981512
TI  - [Guidelines for self-monitoring of blood pressure at home].

PMID- 16981513
TI  - [Present status of home blood pressure monitoring].

PMID- 16981514
TI  - [Prognostic significance of home blood pressure monitoring for stroke].

PMID- 16981515
TI  - [Value of home blood pressure can also predict a loss of functional independence
      in the community-dwelling elderly aged 75 years or older].

PMID- 16981516
TI  - [Improvement in medication compliance by home blood pressure measurement].

PMID- 16981517
TI  - [Dipper and non-dipper].

PMID- 16981518
TI  - [Morning surge].

PMID- 16981519
TI  - [Morning blood pressure variability and autonomic nervous activity].

PMID- 16981520
TI  - [Morning hypertension].

PMID- 16981521
TI  - [Development of micro-ABPM device].

PMID- 16981522
TI  - [White coat hypertension].

PMID- 16981523
TI  - [Reverse white-coat hypertension].

PMID- 16981524
TI  - [Recent reports of the Framingham study].

PMID- 16981525
TI  - [Changes in cardiovascular risk factors and their impact].

PMID- 16981526
TI  - [Prediction of the development of hypertension].

PMID- 16981527
TI  - [The Ohasama study].

PMID- 16981528
TI  - [Tanno-Sobetsu chou study].

PMID- 16981529
TI  - [NIPPON DATA].

PMID- 16981530
TI  - [J-TOPP].

PMID- 16981531
TI  - [The JMS cohort study].

PMID- 16981532
TI  - [Epidemiological study on cardiovascular and renal diseases in Okinawa].

PMID- 16981533
TI  - [Oxidative stress marker].

PMID- 16981534
TI  - [Pulse wave velocity and hypertension].

PMID- 16981535
TI  - [Carotid arterial stiffness parameter].

PMID- 16981536
TI  - [FPW, RPW, augmentation index].

PMID- 16981537
TI  - [Endothelial function].

PMID- 16981538
TI  - [MMP/TIMP ratio and hypertensive target organ damage].

PMID- 16981539
TI  - [Electrocardiographic findings].

PMID- 16981540
TI  - [Echocardiography--latest topic].

PMID- 16981541
TI  - [Heart diseases complicated with hypertension].

PMID- 16981542
TI  - [Hypertension and renal dysfunction].

PMID- 16981543
TI  - [Cerebrovascular disease complicated with hypertension].

PMID- 16981544
TI  - [Ocular complications in patients with hypertension].

PMID- 16981545
TI  - [Introduction to lifestyle modifications for hypertension].

PMID- 16981546
TI  - [Preventive hypertension education program].

PMID- 16981547
TI  - [Dietary salt restriction for patients with hypertension].

PMID- 16981548
TI  - [Other dietary management for patients with hypertension].

PMID- 16981549
TI  - [Exercise and hypertension].

PMID- 16981550
TI  - [Lifestyle modification for patients with hypertension: alcohol restriction].

PMID- 16981551
TI  - [Smoking and hypertension].

PMID- 16981552
TI  - [Prescribing trends in antihypertensive drugs].

PMID- 16981553
TI  - [Predicting factors for antihypertensive response to drugs].

PMID- 16981554
TI  - [Pharmacoeconomic issues in antihypertensive treatment].

PMID- 16981555
TI  - [Medication guidance for patients with hypertension].

PMID- 16981556
TI  - [Usefulness of diuretics for hypertensive patients].

PMID- 16981557
TI  - [Medical economics of antihypertensive agents].

PMID- 16981558
TI  - [Evidence of antihypertensive therapy with diuretics].

PMID- 16981559
TI  - [Alpha adrenergic receptor blockers for patients with hypertension].

PMID- 16981560
TI  - [Alpha beta-blockers for patients with hypertension].

PMID- 16981561
TI  - [ACE-I for patients with hypertension].

PMID- 16981562
TI  - [ARB for patients with hypertension].

PMID- 16981563
TI  - [Combination therapy in hypertension].

PMID- 16981564
TI  - [Characteristics of elderly hypertension].

PMID- 16981565
TI  - [Prognosis of elderly hypertension].

PMID- 16981566
TI  - [Resistant hypertension].

PMID- 16981567
TI  - [Management of hypertension in patients with acute stroke].

PMID- 16981568
TI  - [Blood pressure control in chronic stroke].

PMID- 16981569
TI  - [Large-scale trials in hypertension: clinical relevance and evaluation].

PMID- 16981570
TI  - [ALLHAT].

PMID- 16981571
TI  - [LIFE].

PMID- 16981572
TI  - [ANBP-2].

PMID- 16981574
TI  - [Study on cognition and prognosis in the elderly].

PMID- 16981573
TI  - [VALUE].

PMID- 16981575
TI  - [CHARM].

PMID- 16981576
TI  - [Blood pressure lowering effects of DASH diet as a life style modification].

PMID- 16981577
TI  - [JATOS].

PMID- 16981578
TI  - [CASE-J].

PMID- 16981579
TI  - [VALISH].

PMID- 16981580
TI  - [COPE trial].

PMID- 16981581
TI  - [E-COST].

PMID- 16981582
TI  - [Background for the revision of JSH2004].

PMID- 16981583
TI  - [Measurement and evaluation of blood pressure].

PMID- 16981584
TI  - [Choice of antihypertensive drugs].

PMID- 16981585
TI  - [Treatment for hypertension with metabolic disorders (DM etc)].

PMID- 16981586
TI  - [Therapy of hypertension associated with organ damage].

PMID- 16981587
TI  - [Treatment of hypertension in the elderly].

PMID- 16981588
TI  - [Comparison of guidelines for hypertension therapy in each country].

PMID- 16981589
TI  - [JNC 7].

PMID- 16981590
TI  - [WHO/ISH 2003].

PMID- 16981591
TI  - [ESH/ESC 2003].

PMID- 16981592
TI  - The long-term consequences of antiretroviral therapy.

PMID- 16981593
TI  - The long-term consequences of antiretroviral therapy: a review.

PMID- 16981594
TI  - The impact of antiretroviral therapy on AIDS and survival.

PMID- 16981595
TI  - HIV Congress 2006, Mumbai, India, 10-12 March 2006.

PMID- 16981596
TI  - A four-year prospective study of cognitive functioning in Huntington's disease.
AB  - The contribution of neurologic, genetic, and demographic variables to decline in
      cognition was examined in 70 early- to mid-stage patients with Huntington's
      disease (HD) using random effects modeling. Study participants were followed
      prospectively at baseline and at four annual reevaluations. Only modest decline
      was noted on most neuropsychological variables. Neurologic dysfunction, assessed
      using the Quantified Neurologic Examination (QNE), proved to be the strongest
      predictor of cognitive decline. While significantly predictive of more rapid
      decline in neurologic functioning, CAG repeat length was not generally related to
      cognitive decline after adjusting for QNE, with the exception of performance on a
      single test of visual scanning and psychomotor speed (i.e., Trail Making Test,
      Part A). We propose that CAG repeat length is more closely linked with changes in
      basal ganglia that predominate in early- to mid-stage HD than with cortical
      degeneration seen later in disease progression. Such a relationship would explain
      the predictive value that CAG repeat length plays in changes associated with
      automatic motor response programs (e.g., QNE and Trail Making Test, Part A) but
      not in dysfunction on tasks requiring higher-order processing.

PMID- 16981597
TI  - Saccadic trajectory in Huntington's disease.
AB  - Trajectories of saccadic eye movements can be modulated by the presence of a
      competing visual distractor. It is proposed that the superior colliculus (SC)
      controls the initial deviation through competitive lateral interactions. Given
      the ramifications of connections between basal ganglia (BG) thalamo-cortical
      circuitry and the SC, it was anticipated that this modulation would be
      differentially effected in those with Huntington's disease, which in its early
      stages is primarily a disorder of the BG. Horizontal deviation was determined for
      exogenously driven and endogenously driven vertical saccades in the presence of
      peripheral distractors. For neurologically healthy participants, the initial
      trajectories of both saccade types curved away from distractor locations, as
      predicted. However, for HD participants exogenous saccades consistently deviated
      leftwards, irrespective of distractor location. Endogenous saccades also revealed
      anomalous horizontal deviation, with significant leftward deviation evident for
      saccades directed upward and significant rightward deviation for saccades
      directed downward. Further, both groups generated a comparable proportion of
      erroneous responses to distractor stimuli, but only neurologically healthy
      participants demonstrated a response time advantage for compatible
      target/distractor presentation. These results suggest anomalous regulation of
      distractor-related activity in HD.

PMID- 16981598
TI  - Perceptual organization and visual immediate memory in children with specific
      language impairment.
AB  - Children with specific language impairment (LI) have deficits on some nonverbal
      tasks, but it is not clear if these are related to specific visuospatial deficits
      or to more general deficits in processing strategies. Children with LI were given
      two visuospatial tasks that we have shown to be sensitive to strategy use as well
      as specific processing deficits. In Study 1, children with LI (N=29, ages 6 to 12
      years) performed significantly worse than typically developing children (N=26) on
      the Hierarchical Forms Memory task. In Study 2, children with LI (N=15; ages 9 to
      12 years) performed significantly worse than typically developing children (N=40)
      on the Rey-Osterrieth Complex Figure task. Children with LI were less accurate
      and tended to use a fairly piecemeal (immature) strategy when copying the figure
      and were less likely to draw the core rectangle in a more integrated fashion
      during the immediate memory condition. These results suggest children with LI
      have subtle deficits on visuospatial tasks that may be more indicative of
      limitations associated with processing load and planning than of specific
      visuospatial processing deficits.

PMID- 16981599
TI  - The impact of motivation on neuropsychological performance in sports-related mild
      traumatic brain injury.
AB  - The current project examined the impact of differential motivation on baseline
      versus post-mild traumatic brain injury (MTBI) neuropsychological measures in
      athletes. Collegiate athletes were administered a neuropsychological battery
      prior to and post-MTBI. High Motivation at Baseline (HMB) and Suspect Motivation
      at Baseline (SMB) groups were established for each measure based on whether
      baseline performance fell +/- one or more standard deviations from the mean of
      the given measure. Greater improvement was expected in the SMB group than the HMB
      group given hypothesized differences in baseline motivation. In repeated measures
      analysis of covariance (ANCOVA) that removed achievement performance, the SMB
      groups demonstrated greater improvement than the HMB groups for the Trail Making
      Test A & B (TMT-A & B), Digit Span, and Stroop-Color Word (Stroop-CW) tests.
      Also, the percentage of participants who improved according to reliable change
      indices was greater for the SMB groups on the TMT-A & B, Stroop-CW, and the
      Vigil. These findings are likely due to lower motivation in the SMB group for
      each test. However, results also suggest that some tests may be relatively
      unaffected by motivation. These data may have clinical implications and point to
      the need for better methods of identifying athletes with suspect motivation at
      baseline.

PMID- 16981600
TI  - Presentation modality influences behavioral measures of alerting, orienting, and
      executive control.
AB  - The Attention Network Test (ANT) uses visual stimuli to separately assess the
      attentional skills of alerting (improved performance following a warning cue),
      spatial orienting (an additional benefit when the warning cue also cues target
      location), and executive control (impaired performance when a target stimulus
      contains conflicting information). This study contrasted performance on auditory
      and visual versions of the ANT to determine whether the measures it obtains are
      influenced by presentation modality. Forty healthy volunteers completed both
      auditory and visual tests. Reaction-time measures of executive control were of a
      similar magnitude and significantly correlated, suggesting that executive control
      might be a supramodal resource. Measures of alerting were also comparable across
      tasks. In contrast, spatial-orienting benefits were obtained only in the visual
      task. Auditory spatial cues did not improve response times to auditory targets
      presented at the cued location. The different spatial-orienting measures could
      reflect either separate orienting resources for each perceptual modality, or an
      interaction between a supramodal orienting resource and modality-specific
      perceptual processing.

PMID- 16981601
TI  - Subject-performed tasks improve associative learning in amnestic mild cognitive
      impairment.
AB  - Subject-performed tasks (SPTs) may facilitate the deficit in associative learning
      among individuals with amnestic mild cognitive impairment (aMCI) by inducing
      episodic integration of object-action associations. To test this hypothesis, we
      examined free recall and recognition memory following enactment and verbal
      encoding in healthy elderly controls and individuals with aMCI. Study lists
      contained either semantically integrated ("Bounce the ball") or crossed object
      action commands, in which episodic and semantic associations were placed in
      opposition ("Pet the compass"). Associative learning was indeed better after SPT
      than verbal encoding and with integrated relative to crossed lists for the aMCI
      group, as it was for controls. Moreover, the degree to which SPTs reduced the
      semantic interference inherent in the crossed conditions was equivalent for the
      two groups. The results showed that enactment facilitates formation of episodic
      associations, even when not supported by preexisting semantic knowledge, and even
      among individuals who have particular difficulty forming new associations.

PMID- 16981602
TI  - Sex differences in clustering and switching in verbal fluency tasks.
AB  - Sex differences in executive speech tasks, favoring women, have been noted in
      behavioral studies and functional imaging studies. In the present study, the
      clustering and switching components of semantic and phonemic verbal fluency tests
      were examined in 40 healthy men and 40 healthy women. Possible sex differences in
      the influence of cognitive factors such as speed of information processing, word
      knowledge, and/or verbal long-term memory on these verbal fluency factors were
      also assessed. The results showed that women switched more often between
      categories in the phonemic fluency test, whereas men showed a trend toward a
      larger cluster size leading to a smaller total number of words generated.
      Additionally, higher performance on the Digit Symbol test was associated with
      better performance on the semantic and phonemic verbal fluency test in men,
      whereas in women, better memory performance was associated with better
      performance on these verbal fluency tests. Our data indicate that men and women
      are using different processing strategies for phonemic verbal fluency tests to
      optimize verbal fluency task performance. In the current study, women adopted a
      more successful strategy of balancing clustering and switching in the phonemic
      fluency task.

PMID- 16981603
TI  - Differential disruptions of working memory components in schizophrenia in an
      object-location binding task using the suppression paradigm.
AB  - Patients with schizophrenia exhibit normal memory for separate objects or
      locations but are disproportionately impaired when the items must be bound for
      later recognition in a working memory (WM) setting (Burglen et al., 2004). This
      study aimed at further evaluating the contribution of each WM component to the
      patients' binding deficit, using selective articulatory, visuospatial, and
      executive suppression tasks. In the object-location binding task used, a trial
      comprised the successive presentation of three drawings of familiar objects and
      of three spatial locations in a grid, either separately (i.e., objects alone or
      locations alone) or bound (i.e., object+location), and required a recognition
      test following an 8-s delay. In the suppression modalities, suppression was
      continuous from presentation to test. A total of 22 patients with schizophrenia
      and 24 healthy controls participated. The results confirmed the binding deficit
      in patients' performance in the baseline modality where no suppression was
      required. They also showed that patients were particularly disrupted when
      suppression was visuospatial. This last finding extends the specific visuospatial
      vulnerability in schizophrenia to the operations of binding.

PMID- 16981604
TI  - Comparing attentional skills in children with acquired and developmental central
      nervous system disorders.
AB  - Attentional impairments in children occur in the context of both developmental
      and acquired disorders involving the central nervous system (CNS) and may have
      implications for ongoing development, potentially impeding cognitive,
      educational, and behavioral functions. Using a continuous performance paradigm
      (CPT), this study compared attentional profiles of children with developmental
      and acquired conditions impacting on the CNS: (i) attention deficit-hyperactivity
      disorder (ADHD: n=27); (ii) moderate traumatic brain injury (TBI: n=41); (iii)
      acute lymphoblastic leukemia (n=31); and (iv) insulin-dependent diabetes mellitus
      (n=39). A healthy control group (n=46) was also examined. Groups were compared on
      measures of sustained attention, selective attention, and response inhibition. In
      addition, measures of performance variability and deterioration and processing
      speed were examined. Results showed that children with ADHD exhibited global and
      severe attentional impairments in contrast to all other groups. Children with
      moderate TBI displayed mild attentional difficulties, restricted to selective and
      sustained attention domains. In conclusion, although CPT parameters
      differentiated the ADHD group from all others, a disorder-specific profile was
      not observed.

PMID- 16981605
TI  - Distribution of attention in normal people as a function of spatial location:
      right-left, up-down.
AB  - The spatial allocation of attention influences estimates of stimulus magnitude,
      including line length and the line bisection task has been used to assess the
      asymmetrical allocation of spatial attention. The purpose of this study is to
      learn if normal subjects' allocation of attention changes as a function of the
      trunk-head centered spatial position of the line stimuli. Normal subjects were
      asked to bisect lines placed in five different head-trunk centered special
      positions (central, right up-distal, left up-distal, right down-proximal, left
      down-proximal). When compared with the central condition, deviations in the right
      or left lateral conditions were only significant in the down-proximal conditions,
      such that the bisection bias significantly shifted direction to the left of the
      objective midline in left hemispace and to the right of the objective midline in
      right hemispace, suggesting that stimuli presented in lateral hemispace primarily
      activate the contralateral hemisphere's attentional systems. The finding that the
      lines presented in down-proximal lateral hemispace induce a greater spatial bias
      than lines in up-distal lateral space suggests that the portion of the brain's
      dorsal visual system, which processes stimuli in down-proximal space, influences
      the horizontal (right-left) spatial allocation of attention more than does the
      brain's ventral visual system.

PMID- 16981606
TI  - Forming, switching, and maintaining mental sets among psychopathic offenders
      during verbal and nonverbal tasks: another look at the left-hemisphere activation
      hypothesis.
AB  - Three hypotheses for cognitive deficits among psychopaths were tested: executive
      dysfunction, left hemisphere activation, and an interaction between the two.
      Twenty-one psychopathic and 23 nonpsychopathic criminal offenders identified with
      the Hare Psychopathy Checklist-Revised participated in verbal and visual-spatial
      tasks during which the level of executive processing demands was manipulated.
      Consistent with prior research, psychopathic offenders made more errors than
      controls, but only during the verbal task and only on trials with high executive
      demand. Within those trials, most errors occurred when set-maintenance demands
      were the highest. No response latency differences between groups were found.

PMID- 16981607
TI  - Validity of the minimal assessment of cognitive function in multiple sclerosis
      (MACFIMS).
AB  - Cognitive impairment occurs in roughly 50% of patients with multiple sclerosis
      (MS). It is well known that processing speed and episodic memory deficits are the
      most common neuropsychological (NP) sequelae in this illness. Consensus has
      emerged about the specific tests that prove most helpful for routine monitoring
      of MS associated cognitive impairment. The purpose of this study was to examine
      the validity of the Minimal Assessment of Cognitive Function in MS (MACFIMS), a
      recommended battery based on the findings of an international conference held in
      2001. We tested 291 MS patients and 56 healthy controls. Frequencies of
      impairment paralleled those reported in previous work for both individual
      cognitive domains and general impairment. All tests were impaired in the MS
      group, and distinguished relapsing-remitting (RR) from secondary progressive (SP)
      course. Principle components analysis showed a distinct episodic memory
      component. Most of the MACFIMS tests discriminated disabled from employed
      patients. However, in regression models accounting for all NP tests, those
      emphasizing verbal memory and executive function were most predictive of
      vocational status. We conclude that the MACFIMS is a valid approach to routine NP
      assessment of MS patients. Future work is planned to determine its psychometric
      properties in a longitudinal study.

PMID- 16981608
TI  - The effects of reward and punishment contingencies on decision-making in multiple
      sclerosis.
AB  - Many patients with multiple sclerosis (MS) show cognitive and emotional
      disorders. The purpose of this study is to evaluate the role of contingency
      learning in decision-making in young, non-depressed, highly functioning patients
      with MS (n=21) and in matched healthy controls (n=30). Executive functions,
      attention, short-term memory, speed of information processing, and selection and
      retrieval of linguistic material were also investigated. Contingency learning
      based on the cumulative effect of reward and punishment was assessed using the
      Iowa Gambling Test (IGT). In the classic ABCD version of the IGT, advantageous
      decks are characterized by immediate small reward but even smaller future
      punishment. In the modified EFGH version, advantageous decks are characterized by
      immediate large punishment but even larger future reward. Results revealed that
      patients with MS showed significant dysfunctions in both versions of the IGT.
      Performances on neuropsychological tests sensitive to dorsolateral prefrontal
      functions did not predict and did not correlate with the IGT scores. These
      results suggest that patients with MS show impaired performances on tasks
      designed to assess decision-making in a situation requiring the evaluation of
      long-term outcomes regardless of gain or loss, and that this deficit is not a
      pure consequence of executive dysfunctions.

PMID- 16981609
TI  - Processing of local and global visual features in obsessive-compulsive disorder.
AB  - Research conducted with the Rey-figure task has suggested that patients with
      obsessive-compulsive disorder (OCD) process local aspects of a complex stimulus
      more efficiently than the overall gestalt. The aim of the present study was to
      investigate if this "local bias" is established already during early stimulus
      encoding or occurs only during later processing, once a percept has been formed
      (e.g., memory retrieval). To this end, responding to local and global targets of
      hierarchical letters (e.g., an "E" composed out of small "T"s) was assessed in 30
      OCD patients and 28 healthy controls. OCD patients and controls performed
      comparably on all parameters. These results lend no support to the notion of an
      early perceptual bias towards local elements in OCD patients. It remains to be
      tested whether a bias towards local features is confined to situations where
      local and global features compete for selection.

PMID- 16981610
TI  - Verbal fluency patterns in amnestic mild cognitive impairment are characteristic
      of Alzheimer's type dementia.
AB  - Amnestic mild cognitive impairment (aMCI) represents a high-risk factor for
      Alzheimer's disease (AD) and is characterized by a selective decline in episodic
      memory. Although by definition aMCI is not associated with impaired verbal
      fluency performance, we examined relative differences between fluency tasks
      because AD is characterized by poorer semantic than phonemic fluency. Phonemic
      and semantic fluency trials were administered to 46 healthy controls, 33 patients
      with aMCI, and 33 patients with AD. Results revealed a progressive advantage
      (controls > aMCI > AD) in semantic, relative to phonemic fluency. Difference
      scores between tasks distinguished each group from the others with medium to
      large effect sizes (d) ranging from 0.49 to 1.07. Semantic fluency relies more on
      semantic associations between category exemplars than does phonemic fluency. This
      aMCI fluency pattern reflects degradation of semantic networks demonstrating that
      initial neuropathology may extend beyond known early changes in hippocampal
      regions.

PMID- 16981611
TI  - Multitasking performance of Chinese children with ADHD.
AB  - The aim of this study was to explore multitasking skills in a Chinese sample of
      22 children with attention deficit-hyperactivity disorder (ADHD) compared with 22
      healthy controls matched by gender, age, and IQ. All of the participants
      completed the children's version of the Six Elements Test (C-SET) and
      neuropsychological tests that captured specific domains of attention, memory, and
      executive function. Children with ADHD performed significantly worse than the
      healthy controls in all domains except the number of rules broken in the C-SET.
      The majority of the C-SET domain scores correlated significantly with measures of
      executive function. The ADHD group also demonstrated deficits in various
      neurocognitive test performances compared with the healthy group. This
      preliminary study suggests that the C-SET is sensitive to multitasking behavior
      in Chinese children with ADHD. The main impairments of multitasking behavior in
      this clinical group involve the inhibition of goal-directed planning, flexible
      strategy generation, and self-monitoring.

PMID- 16981612
TI  - Hand movement span after mild traumatic brain injury: a longitudinal study.
AB  - This study examined whether memory span was impaired during the acute and post
      acute phases following mild traumatic brain injury (mTBI). Twenty-two adults with
      mTBI were compared with 22 controls on computerized tasks of immediate memory for
      verbal, spatial, and hand movement sequences under no interference (baseline) and
      articulatory suppression conditions. Groups were assessed within a month and
      followed up 3-12 months post-injury. In the acute phase, there were no group
      differences across tasks under either condition. At follow-up, all spatial and
      verbal span scores and associated practice effects were equivalent across groups.
      Yet for the hand movement task, baseline movement span was worse for the mTBI
      group suggesting that they failed to benefit from practice to the same extent as
      controls. Furthermore, the fact that this group difference in span scores
      disappeared when articulatory suppression was imposed indicates that successful
      hand movement task performance involves verbal recoding.

PMID- 16981613
TI  - The relationship between childhood sexual abuse and sexual health practices of
      homeless adolescents.
AB  - This study explored the gender differences in sexual self-concept, personal
      resources for sexual health, safe sex behaviors, and risky sexual behaviors among
      homeless adolescents with and without histories of sexual abuse. Data for this
      secondary analysis were collected in 2003 to 2004 in the first phase of a larger
      repeated-measures sexual health intervention study; 371 homeless youth between 16
      and 23 years of age (M = 19.26, SD = 1.83) were recruited from a street outreach
      center. The majority (64.6%) of participants were males. Self-report instruments
      were completed at the outreach center via audio computer-assisted self-interview
      (A-CASI) format. It was found that female participants were better off than males
      on numerous measures of sexual health behaviors and attitudes. Sexually abused
      participants had significantly less future time perspective (p = .05), fewer
      sexual self-care behaviors (p = .04), and less social support than nonabused
      participants (p = .01) and almost significantly more sexual risk-taking (p =
      .08). However, no significant differences were found between abused and nonabused
      participants on sexual self-concept, self-efficacy or intention to use condoms,
      safe sex behaviors, AIDS knowledge, assertive communication, or self-efficacy to
      perform testicular/ breast self-exams. Overall, participants who did not report a
      history of sexual abuse had significantly more sexual health resources and
      engaged in fewer sex-risk behaviors than those who reported having been abused.
      These differences have notable implications for screening adolescents for a
      history of sexual abuse. Adolescents who report sexual abuse should receive risk
      counseling and be screened regularly for the development of sexual risk
      behaviors.

PMID- 16981614
TI  - Dropout policies and trends for students with and without disabilities.
AB  - Students with and without disabilities are dropping out of school at an alarming
      rate. However, the precise extent of the problem remains elusive because
      individual schools, school districts, and state departments of education often
      use different definitional criteria and calculation methods. In addition,
      specific reasons why students drop out continues to be speculative and minimal
      research exists validating current dropout prevention programs for students with
      and without disabilities. This study examined methods secondary school principals
      used to calculate dropout rates, reasons they believed students dropped out of
      school, and what prevention programs were being used for students with and
      without disabilities. Results indicated that school districts used calculation
      methods that minimized dropout rates, students with and without disabilities
      dropped out for similar reasons, and few empirically validated prevention
      programs were being implemented. Implications for practice and directions for
      future research are discussed.

PMID- 16981615
TI  - Violence and minority youth: the effects of risk and asset factors on fighting
      among African American children and adolescents.
AB  - This cross-sectional study examined risk and asset factors thought to be
      associated with fighting among a sample of 1,642 African American children and
      adolescents in a central Alabama school district. Results show that poor grades,
      parental abuse, and gang affiliation were significant risk factors associated
      with higher frequency of fighting. Results also show that parental monitoring and
      being happy at school were associated with lower frequency of fighting,
      suggesting the importance of continued support for outreach to parents and
      further efforts to reduce or eliminate the community factors that promote
      proliferation of gangs. Programs, either for an entire community or a school
      system within a community, must be sensitive to the specific risks, assets, and
      outcomes of that environment so that prevention and intervention are sensitive to
      cultural, environmental, and demographic distinctions in target populations.

PMID- 16981616
TI  - Ethnic differences in adolescents' mental distress, social stress, and resources.
AB  - Limited data on ethnic group differences among young adolescents exist regarding
      the prevalence of mental distress, social stress, and resources. The aim of this
      cross-sectional study was to examine ethnic differences among African American
      (AA), European American (EA), Hispanic American (HA), and Asian American
      adolescents in mental distress, social stress, and resources. A total of 316
      adolescents completed the self-administered questionnaire: The DSD, Somatic
      Symptom Scale, SAFE-C, FES, Coping, and Rosenberg's Self-Esteem Scale. The
      findings revealed that (1) Asian Americans and HAs reported significantly higher
      scores on social stress and mental distress and lower scores on resources than
      EAs; (2) Compared to EAs, AAs and HAs were more likely to experience social
      stress (2.2 < or = OR < or = 4.3), and HAs are more likely to have suicidal
      ideation (OR = 2.04; 95% CI = 1.04-3.98). Findings highlighted the importance of
      understanding the role of social stress in the development of adolescents' mental
      distress. Identified ethnic minority adolescents are vulnerable groups who
      require additional research and attention from health care providers.

PMID- 16981617
TI  - Xenophobia, ethnic community, and immigrant youths' friendship network formation.
AB  - Immigrant youth often rebuild their friendships and other social networks after
      arriving in a new country. The difficulties involved can threaten their
      psychosocial development. Formation of social networks needs to be understood
      within the macro sociocultural context that shapes the experience. Nonetheless,
      the current literature on social network formation rarely captures that context.
      Knowledge about immigrant youths' social network, for example, is often embedded
      in assimilation, ethnic identity, and adaptation literature. This paper examines
      how the sociocultural context enables immigrant youth to rebuild their friendship
      networks. A critical ethnography was conducted in the northwest region of the
      United States. Sixteen Taiwanese immigrant youth and their parents (N = 13)
      participated in the study. Data collection consisted of semi-structured in-depth
      interviews, a demographic questionnaire, and participant observations. The
      findings showed that because of limited English proficiency, the youth kept at a
      distance from American peers to avoid nervousness and embarassment. Further
      analysis, derived from xenophobia, found that limited English proficiency
      increases segregation between American peers ("we") and immigrant youth ("the
      other"). The English as a Second Language program inadvertently perpetuates the
      immigrants' sense of "otherness" and increases the odds of their becoming targets
      of discrimination. A protective factor for these youths is living near an ethnic
      community because the inclusion of coethnics increases new friendship networks.
      Knowledge about the teen culture in coethnics' countries of origin (China, Hong
      Kong, or the United States), also influences their selection of friends.

PMID- 16981618
TI  - Suicide attempts among adolescent Mexican American students enrolled in special
      education classes.
AB  - Suicide is the second leading cause of death among school-aged students between
      the ages of 15 and 19. There is an increasing frequency of suicide and other self
      destructive behaviors among Mexican American youth and students in special
      education classrooms for emotional and behavioral disabilities. Recognizing
      Mexican American youth in special education classes as a separate risk group,
      this study (a) identifies factors that contribute to suicide, (b) reviews the
      signs and characteristics associated with these factors, (c) interviews Mexican
      American students in special education who have either exhibited various
      characteristics of suicidal thoughts and/or have attempted suicide, (d) explores
      effective prevention programs, and (e) provides suggestions for school personnel.
      Interviews with five adolescent Mexican American special education students
      support previous research findings that depression, substance abuse, social and
      interpersonal conflict, family distress, and school stress are primary
      characteristics related to suicidal minority youth.

PMID- 16981619
TI  - Experiences of school bullying in Northern Ireland: data from the Life and Times
      Survey.
AB  - Little is known about the levels of bully/victim behaviors in schools in Northern
      Ireland. The aim of the present study was to supplement previous research
      findings from Northern Ireland by examining the self-reported experiences of
      school bullying among Northern Ireland children through data collected as part of
      the 1998 "Youth Life and Times Survey." A random sample of 397 12 to 17-year-olds
      living throughout Northern Ireland were interviewed during 1998 and 1999. As part
      of the larger survey, six questions were asked relating to experience of bullying
      behaviors and being a victim of such behaviors. The findings suggests that the
      incidence of school bullying in Northern Ireland may be higher than those found
      in the rest of Ireland and the United Kingdom. Furthermore, the data supplements
      previous findings among Northern Irish children employing alternate measures of
      bully/victim problems.

PMID- 16981620
TI  - Peer groups and substance use: examining the direct and interactive effect of
      leisure activity.
AB  - This paper explores the relationships among adolescent leisure activities, peer
      behavior, and substance use. We suggest that peer group interaction can have a
      differential effect on adolescent deviant behavior depending on the type of
      leisure pattern adolescents engage in. We analyze data from a representative
      national sample of Icelandic adolescents, exploring the variations in the use of
      alcohol and illegal drugs among three different patterns of leisure activity,
      controlling for parental ties and school commitment. The findings show that
      alcohol and substance use varies significantly across the three leisure patterns.
      Moreover, it was found that the well-known relationship between adolescent
      substance use and having substance-using friends is significantly contingent on
      the type of leisure pattern. Our findings suggest that it is important to take
      into account different peer leisure activities in order to understand adolescent
      substance use. Finally, we discuss the implications of the findings for
      prevention work with adolescents.

PMID- 16981621
TI  - Psychological well-being in adolescence: the contribution of interpersonal
      relations and experience of being alone.
AB  - This study investigated the influence of loneliness and relationships with
      parents and friends on the psychological well-being or adolescent malaise. Data
      were collected via two questionnaires (LLCA-Marcoen, Goossens & Caes, 1987; TRI
      Bracken, 1996) from a sample of 330 Italian adolescents, males and females, aged
      between 11 and 19. As hypothesized, results showed that a positive relationship
      with friends and parents promotes psychological well-being in adolescents and
      reduces malaise. In addition, the study showed that the adolescents were able to
      distinguish between different states of loneliness; on one hand they could
      recognize the pain of isolation and social refusal, and on the other, they could
      recognize the pleasant dimension of loneliness, according to the age and sex.
      Therefore loneliness can be a risk for the adolescent's well-being if it is
      caused by social refusal, but it can also be a developmental need (parallel to
      the need for attachment), and can promote psychological well-being when
      adolescents choose to be alone.

PMID- 16981622
TI  - Tobacco consumption and motives for use in Mexican university students.
AB  - Increased tobacco consumption, especially among adolescents and females, has been
      observed recently in Mexico. The goal of this study is to describe tobacco
      consumption and motives for use among university students. A descriptive cross
      sectional study was performed using data provided by 282 students aged 15-24
      studying at the University of Guadalajara's University Center for Health Sciences
      (CUCS). A validated online survey was applied. The study was voluntary,
      anonymous, and confidential; 65.5% of respondents were 20-24 years of age (65.4%
      were females). Students in the upper-middle socioeconomic level comprised 64.5%
      of respondents; 22.3% of students had smoked during the previous month, and 22%
      felt a deep need to smoke during the past year. The motives for smoking varied.
      Dealing with problematic emotional behavior was the reason given by 75.6% of
      smokers; 20.7% of smokers claimed their smoking was a reasoned action, as they
      had healthy friends who smoked. Motives for not smoking also varied; that smoking
      was harmful was cited by 47.7% of respondents. The view that smoking was a
      problematic form of behavior was held by 46.2% of nonsmokers; 29% of students had
      no access to cigarettes. No differences in response frequencies were found
      between males and females.

PMID- 16981623
TI  - The effects of sports participation on young adolescents' emotional well-being.
AB  - This study examined the relationship between children's sports participation and
      emotional well-being including self-reported emotional and behavioral problems
      and multidimensional aspects of self-concept. Data were collected from 203 young
      adolescents using a multitrait-multimethod assessment methodology. Information
      was obtained using a sports questionnaire concerning participation in and
      perceptions of sporting activities. Emotional well-being was assessed by the
      Youth Self-Report (Achenbach, 1991) and the Self-Perception Profile for Children
      (Harter, 1985). The study found that increased levels of sports participation had
      a positive relationship with aspects of emotional and behavioral well-being,
      particularly self-concepts. Results also showed that children with increased
      perceptions of sport-related competencies reported significantly fewer emotional
      and behavioral problems than did children who were, by external standards (e.g.,
      teacher rating, number of sporting achievements), actually competent at sport.
      The study also found particular areas of sports participation to be positively
      associated with self-concept. Evidence suggests a similar beneficial association
      with some aspects of behavior problems. Practical implications of the findings
      are discussed along with recommendations for future research.

PMID- 16981624
TI  - Studying social policy and resilience to adversity in different welfare states:
      Britain and Sweden.
AB  - Is poverty more damaging to health in Britain than in Sweden, and if so, why?
      Following previous research by the authors that suggested such an effect, a new
      comparative study is examining whether there are aspects of the social and policy
      context in Britain that add to and reinforce the health-damaging experience of
      being poor. Conversely, are there other aspects of living in Sweden that are
      supportive for people in poverty, which make the experience of poverty less
      stressful and health-damaging? Stemming from this ongoing study, the aim of this
      article is to present a framework for understanding the context in which social
      welfare policies are formed and operate in Britain and Sweden. It then uses the
      framework to consider the "upstream" influences of ideology, culture, and values
      on policy development in the two countries and what these developments might mean
      for the health and well-being of people facing financial adversity in the two
      societies.

PMID- 16981625
TI  - Basic family budgets: working families' incomes often fail to meet living
      expenses around the United States.
AB  - The ability of families to meet their most basic needs is an important measure of
      economic stability and well-being. While poverty thresholds are used to evaluate
      the extent of serious economic deprivation in our society, family budgets--that
      is, the income a family needs to secure safe and decent-yet-modest living
      standards in the community in which it resides--offer a broader measure of
      economic welfare. Basic family budgets take into account differences in both
      geographic location and family type. In total, this report presents basic budgets
      for more than 400 U.S. communities and six family types (either one or two
      parents with one, two, or three children). That the budgets differ by location is
      important, since certain costs, such as housing, vary significantly depending on
      where one resides. This geographic dimension of family budget measurements offers
      a comparative advantage over using poverty thresholds, which only use a national
      baseline in their measurements.

PMID- 16981626
TI  - Child poverty in rich countries, 2005, Part II.
AB  - Protecting children from the sharpest edges of poverty during their years of
      growth and formation is both the mark of a civilized society and a means of
      addressing some of the evident problems that affect the quality of life in the
      economically developed nations. The proportion of children living in poverty has
      risen in a majority of the world's developed economies over the past decade. This
      report asks what is driving poverty rates upwards and why some OECD countries are
      doing a much better job than others in protecting children at risk.

PMID- 16981627
TI  - The dialectics of childhood diarrhea mortality.
AB  - As in European countries a century ago, diarrhea is a major cause of child
      mortality in poor countries today. In Stockholm at the turn of the 19th century,
      political commitment, infrastructural investments in water and sanitation, and
      enforcement of sanitary improvements by a strong implementing organization helped
      eliminate diarrhea as a principal cause of death among children. These
      interventions also had an equitable impact on social class differences in
      diarrhea mortality, but not on overall mortality; overall mortality declined, but
      class differences remained. General infrastructural improvement and health
      education coupled with targeted interventions to vulnerable children may be
      successful in improving child health and reducing social differentials in
      mortality. Specific health care interventions may need to be complemented by
      infrastructural investments to improve water and sanitation if diarrhea mortality
      is to be further reduced in poor countries today.

PMID- 16981628
TI  - Depleted uranium: all the questions about DU and Gulf War syndrome are not yet
      answered.
AB  - For 15 years, the debate about depleted uranium (DU) and its detrimental effects
      on the health of veterans of the Gulf War of 1991, on the Iraqi people and
      military (and subsequently on the people of Kosovo, Afghanistan, and Iraq during
      the second war) has remained unresolved. Meanwhile, the number of Gulf War
      veterans who have developed the so-called Gulf War syndrome has risen to about
      one-third of the 800,000 U.S. forces deployed, and unknown proportions of those
      involved in the subsequent wars. Uncounted civilians and personnel of other
      nations that fought in Iraq and other wars since 1991 have also been afflicted.
      The veterans have suffered from multiple serious physiological disorders and have
      received little or no official recognition, medical relief, or compensation. We
      need to take another look at this issue, using a holistic and interactive model
      for the toxic matrix of exposures, identifying the major roadblocks to resolving
      the scientific questions, and finding appropriate medical and political
      responses. This commentary is such an attempt.

PMID- 16981629
TI  - Hitting home: a survey of housing conditions of homes used for long-term care in
      Ontario.
AB  - A telephone survey of a random sample of 811 long-term home care clients from
      three geographically distinct regions in Ontario was conducted to illuminate the
      living and working conditions in households receiving long-term care services.
      The median age of clients was 77 years and 75 percent were female. The majority
      had not completed high school. Almost half were widowed, had income levels of
      dollar 20,000 (Canadian) or less, and lived alone. Approximately one-third needed
      help with most basic activities of daily living. The vast majority could not
      bathe or dress themselves. More than three-quarters needed help with preparing
      meals, housekeeping, and shopping. Few clients could perform yardwork and home
      repairs. Many clients' homes required major and minor repairs, were not suitable
      in size, were not affordable, and lacked important household amenities. More than
      30 percent required modifications to enable clients to live and be cared for
      comfortably and safely, and half the clients had not completed these because of
      exorbitant costs. Overall, many clients were living in homes less than optimal
      for domestic life and long-term care provision. These results highlight
      significant gaps in care provision and a need to link housing to health and
      social service policies.

PMID- 16981630
TI  - Silenced complaints, suppressed expectations: the cumulative effects of home care
      rationing.
AB  - In many Western welfare jurisdictions, publicly provided home care is being
      eroded and its provision increasingly individualized. These shifts are of a
      particular significance for older women, a group for whom supportive home care
      has been an important buttress against the social and physical jeopardies of old
      age. A longitudinal, qualitative study of such women in Ontario, Canada, spanned
      the implementation of managed competition in home care and a period of rapid
      privatization and service rationing. Study participants experienced cuts and,
      stemming from increasingly precarious employment conditions in the home care
      workforce, inconsistent care providers. These changes generated distress,
      insecurity, and isolation in participants' lives. This article explores how their
      complaints about insufficient care were silenced: by fear, hopelessness, and the
      cultural injunction to put a stoic and selfless face on the limitations of old
      age. Their accounts reveal how large material and discursive shifts and state
      restructuring come to penetrate identity, feeling, and speech. This examination
      of the silencing of complaint at home care's front lines reveals the cumulative
      effects of rationing; it also illuminates how, if heard, service users' voices
      can inform collective struggles to resist the degradation of home care and
      reposition older people in relation to the state.

PMID- 16981631
TI  - Reifying human difference: the debate on genetics, race, and health.
AB  - The causes of racial and ethnic inequalities in health and the most appropriate
      categories to use to address health inequality have been the subject of heated
      debate in recent years. At the same time, genetic explanations for racial
      disparities have figured prominently in the scientific and popular press since
      the announcement of the sequencing of the human genome. To understand how such
      explanations assumed prominence, this essay analyzes the circulation of ideas
      about race and genetics and the rhetorical strategies used by authors of key
      texts to shape the debate. The authority of genetic accounts for racial and
      ethnic difference in disease, the author argues, is rooted in a broad cultural
      faith in the promise of genetics to solve problems of human disease and the inner
      truth of human beings that is intertwined with historical meanings attached to
      race. Such accounts are problematic for a variety of reasons. Importantly, they
      produce, reify, and naturalize notions of racial difference, provide a scientific
      rationale for racially targeted medical care, and distract attention from
      research that probes the complex ways in which political, economic, social, and
      biological factors, especially those of inequality and racism, cause health
      disparities.

PMID- 16981632
TI  - Understanding women, health, and social change: the case of South Korea.
AB  - Since the 1960s, South Korea has experienced rapid economic development and an
      improvement in the health of its population. During this period there have been
      marked increases in women's educational and occupational opportunities. But
      despite these improvements, women still suffer higher levels of gender
      discrimination than their counterparts in many other countries at similar stages
      of development. Most dramatically, there are still high levels of sex-selective
      abortion. Women have lower socioeconomic status than men, and their lives are
      markedly restricted by the cultural values associated with Confucianism. This
      article explores the effects of these factors on women's health. Despite their
      greater longevity, South Korean women still report higher rates of morbidity and
      distress than men. This can be compared with the "gender paradox" in health
      reported in many developed countries during the 1970s and 1980s. More detailed
      research is needed on the factors influencing the health of South Korean women
      and on related trends in other newly industrializing Asian societies.

PMID- 16981633
TI  - Families in today's world-and tomorrow's.
AB  - The world's family systems derive from the great world religions and the cultural
      history of civilizations. On this basis, five fundamental family systems of the
      world can be identified--those of East, South, and West Asia (with North Africa),
      sub-Saharan Africa, and Europe--together with two important interstitial or
      hybrid systems--of Creole America and of Southeast Asia--each with significant
      subvariants. The comparative overview of these seven family systems looks at
      their internal power relations (patriarchy), their marriage patterns and
      regulation of sexuality, and their fertility. Changes tend to move in the same
      direction across the world, but without convergence.

PMID- 16981634
TI  - Explaining paralysis in Chile's health sector, 1990-2000.
AB  - This article looks at the health sector in Chile between 1990 and 2000 to examine
      the obstacles that policymakers face in implementing reforms. Given that the
      health sector is highly politicized, it is important to pay attention not only to
      what kind of reforms are needed but even more to how the desired reforms may be
      implemented. The author identifies the key actors in the Chilean health sector
      and shows how the given politico-institutional context allowed them to obstruct
      reforms. As a result, the health sector came to be characterized by paralysis,
      despite widespread recognition that reforms were needed, and despite an awareness
      that large numbers of Chileans were more concerned about health than political
      issues.

PMID- 16981635
TI  - Distortion of some of the basic principles of public health practice in India.
AB  - India's political leadership has chosen personnel from the Indian Administrative
      Service cadre of generalist administrators and from the clinician-dominated cadre
      of the Central Health Services to run the country's health service system. The
      personnel's inadequate or distorted understanding of some of the basic principles
      of public health practice--such as developing an epidemiological approach to
      solving community health problems, choice of appropriate technology, and
      optimization of health service systems--has had a very deleterious effect on the
      health service system. These administrators have become vulnerable to
      manipulation by personnel from international agencies, who also have questionable
      public health credentials, to create space for imposition of their technocentric,
      ill-conceived, and ill-designed agenda. To rationalize adoption of such an
      obviously faulty agenda, they have to be ahistorical, apolitical, and
      atheoretical and indulge in misinformation, disinformation, and suppression and
      manipulation of information. This amounts to what Navarro has termed
      "intellectual fascism."

PMID- 16981636
TI  - Having fun in the second modernization.
AB  - This study investigates the reasons given by Finnish adolescents for their own
      alcohol use, and for the use of alcohol by others. In 1999, a questionnaire on
      reasons for drugs use was administered to a sample of adolescents aged 14-16
      (N=488). It was found that the reasons given (i.e., attributions) involving inner
      subjective experiences, referring to the "good feeling" and "fun" resulting from
      alcohol use are common.

PMID- 16981637
TI  - Influencing alcohol control policies and practices at community festivals.
AB  - The goal of this study was to assess the feasibility and effectiveness of two
      interventions aimed at reducing alcohol-related risks at community festivals--a
      training program for festival planners and a community organizing campaign. We
      randomly selected four festivals for each intervention and had 24 comparison
      festivals. Our assessment included process evaluation to track and evaluate types
      of alcohol policies resulting from each of the interventions, pre and post
      telephone surveys of key festival planners and law enforcement agencies, and pre
      and post pseudo-underage and pseudo-intoxicated purchase attempts. Analyses
      showed that both interventions were feasible and were successful in influencing
      adoption of written policies and improving alcohol-related practices. However,
      neither intervention appeared to decrease propensity for illegal alcohol sales at
      these events, likely due, in part, to the short time frame of the interventions.
      Future research should assess effects of the interventions on alcohol-related
      problems and effects of enforcement interventions.

PMID- 16981638
TI  - Prescription drug abuse information in D.A.R.E.
AB  - This investigation was designed to examine prescription drug-related content and
      learning objectives in Drug Abuse Resistance Education (D.A.R.E.) for upper
      elementary and middle schools. Specific prescription-drug topics and context
      associated with content and objectives were coded. The coding system for topics
      included 126 topics organized within 14 categories. A two-dimensional coding
      system for context identified Use versus Abuse and Explicit versus Implicit
      references to prescription drugs. Results indicated that content and objectives
      found in D.A.R.E. represent a very narrow breadth of prescription drug topics.
      Moreover, all prescription-drug related content and objectives were presented in
      an Abuse-Implicit context. Although some educational material in D.A.R.E. modules
      potentially is related to prescription drugs, none of the content or objectives
      explicitly identify drugs discussed as prescription drugs. If elementary and
      middle schools rely on D.A.R.E. modules to teach students about drug abuse,
      students are likely to be underinformed about prescription drug risks.

PMID- 16981639
TI  - The five-factor model of personality and smoking: a meta-analysis.
AB  - This article describes a meta-analysis of the relationship between the Five
      Factor Model of personality and smoking. The results, based on nine studies and a
      total of 4730 participants, show that smoking was associated with the following
      five-factor traits: low conscientiousness, low agreeableness, and high
      neuroticism. Smokers outside Canada and the United States had significantly
      higher extraversion than nonsmokers, while extraversion was not significantly
      related to smoking in Canada and the United States. The results, which for the
      first time quantified precisely through meta-analysis the association between the
      five-factor model of personality and smoking, provide support for the relevance
      of the Five-Factor Model to an important behavior and for the trait element of
      Gilbert's (1995) Situation-Trait-Adaptation-Response model of smoking. The
      results also suggest possible avenues for smoking prevention and treatment and
      for further smoking research.

PMID- 16981640
TI  - The effects of fatal vision goggles on drinking and driving intentions in college
      students.
AB  - The present study was designed to examine the effectiveness of Fatal Vision
      Goggles in reducing intentions to drink and drive. Participants performed a field
      sobriety task and drove in a traffic simulator while wearing the goggles. A
      regression analysis was performed in order to predict changes in intentions to
      drink and drive, using typical drinking patterns, perceived likelihood of getting
      into a collision when drinking and driving, self efficacy, and driving
      independence as predictor variables. Results showed that drinking and driving
      intentions were reduced following the use of Fatal Vision Goggles among those
      that typically drink more during outings, among those that believe the likelihood
      of collisions when drinking and driving are greater, and among those less likely
      to drive to achieve independence and autonomy. These results indicate that Fatal
      Vision Goggles can be an effective tool in altering drinking and driving
      attitudes among drivers with specific attitudinal and personal characteristics.

PMID- 16981641
TI  - Alcohol-related incident guardianship and undergraduate college parties:
      enhancing the social norms marketing approach.
AB  - This randomized experiment examines the effects of contextual information on
      undergraduate college student's levels of alcohol-related incident guardianship
      at college parties. The research is conceptualized using routine activities
      theory and the theory of planned behavior. The experiment examines attitudinal
      variations about heavy drinking differentiated by sex, athletic status, and
      location of the drinking event. The sex and athletic status variables produce
      statistically effects on the dependent variables, while location of the drinking
      event is not significant. The article concludes by discussing the importance of
      context as it pertains to the social norms marketing strategy utilized in much
      college alcohol programming, and suggests a more directed marketing approach.

PMID- 16981642
TI  - Heavy alcohol use compared to alcohol and marijuana use: do college students
      experience a difference in substance use problems?
AB  - This study examines the risk for alcohol and other drug (AOD) problems resulting
      from alcohol plus marijuana use compared to alcohol-only use. Data are from
      telephone interviews with 1113 randomly selected college students attending two
      large urban universities in the southwestern United States. Alcohol and marijuana
      users (dual users) were more likely to be younger and report a higher mean number
      of drinks per occasion and experiencing all AOD problems studied compared to
      alcohol-only users. Multivariate logistic regression analysis findings reveal the
      relationship between dual-substance use and increased risk for AOD problems
      remained after controlling for demographics and alcohol use behaviors. Such
      problems include greater odds of legal problems and riding with or being an
      intoxicated driver. College students using alcohol and marijuana are at much
      higher risk for AOD problems than are students who use alcohol only, even when
      heavy drinking is taken into account.

PMID- 16981644
TI  - Production of anti-digoxigenin antibody HRP conjugate for PCR-ELISA DIG detection
      system.
AB  - There are several methods used to visualize the end product of polymerase chain
      reactions. One of these methods is an ELISA-based detection system (PCR-ELISA)
      which is very sensitive and can be used to measure the PCR products
      quantitatively by a colorimetric method. According to this technique, copies of
      DNA segments from genomic DNA are amplified by PCR with incorporation of
      digoxigenin-11-dUTP. Samples are analyzed in a microtiter plate format by
      alkaline denaturation and are hybridized to biotinylated allele-specific capture
      probes bound to streptavidin coated plates. Use of the produced anti-digoxigenin
      antibody horseradish peroxidase conjugate and the substrate 2,2'-azino-di-3
      ethylbenzthiazolinsulfonate (ABTS) detected the hybridized DNA. One of the key
      components in this procedure is the anti-digoxigenin antibody HRP conjugate.
      Described here is the preparation, purification, and characterization of anti
      digoxigenin antibody HRP conjugate for use in the PCR-ELISA DIG detection system.
      Several biochemical protocols and modifications were applied to increase the
      sensitivity and specificity of this conjugate for an efficient and cost-effective
      product.

PMID- 16981643
TI  - Rapid analytical detection of microcystins using gold colloidal
      immunochromatographic strip.
AB  - Routine monitoring of microcystin in natural waters is difficult because the
      concentration of the toxin is low and the detection method is usually
      complicated. We developed a rapid analytical detection method of microcystins
      gold colloidal immunochromatogeraphic strip. The sensitivity of the strip is
      about 1 ng/mL for microcystin LR; it is able to distinguish visually among
      different concentrations of microcystin solutions. The developed gold colloidal
      strip can detect microcystins within 15 min and does not require either a
      complicated extraction system, or trained or qualified experts.

PMID- 16981645
TI  - Comparison between therapeutic antitoxin F(ab)2 fractionated with ammonium
      sulfate and caprylic acid.
AB  - To date, animal derived therapeutic antibodies represent the best and only choice
      source of antitoxins, especially in developing countries. Furthermore, this
      industry needs to develop a production protocol to achieve safer products.
      Recently, several laboratories changed their production protocol from ammonium
      sulfate (AS) protocol to caprylic acid (CA) fractionation. Our results showed
      that using the CA protocol leads to improvement in the product quality, as
      assessed by the albumin and protein content decrease (from 4.75 to 3.54 g/dL and
      0.64 to 0.18 g/dL, respectively), which yielded a purer antitoxin product. The
      F(ab)2 protein aggregate formation and turbidity have been significantly reduced,
      4.60 versus 2.55 and 0.046 versus 0.021 (p < 0.01), respectively. However, the
      anti-complementary activity was also reduced, from 42 to 33. The total IgG
      content was higher in CA fractionated products than AS materials. The endotoxin
      content was worrisome in some F(ab)2 products.

PMID- 16981646
TI  - Detection of serum antibodies to S-antigen by surface plasmon resonance (SPR).
AB  - Serum autoantibodies to visual arrestin, also termed S-antigen, have been shown
      to accompany several autoimmune-related diseases. However, they were also
      detected in sera of healthy individuals; there is lack of a sensitive and fast
      method for evaluation of putative differences between those two groups of
      antibodies. We show that, using biosensor technology based on surface plasmon
      resonance (SPR), it was possible to characterize real-time interactions of immune
      sera with immobilized arrestin. Binding characteristics revealed different
      interaction kinetics of antiarrestin antibodies present in two distinct rabbit
      sera and, thus, broadened results of immunoblotting analysis. Therefore, we
      suggest that SPR-based biosensor technology might be a valuable method for
      monitoring and evaluation of antiarrestin antibodies in patients' sera.

PMID- 16981647
TI  - Assessment of immunometric parameters in malaria: role of enzyme immunoassay.
AB  - Human blood samples collected from local malaria clinics, hospitals, and by cross
      sectional surveys in malaria endemic areas were tested by enzyme immunoassay for
      circulating malarial antigen, antimalarial antibody, and antigen-specific
      circulating immune complexes. The assays were done in serum and finger-prick
      blood absorbed on filter paper. The results obtained from the present study
      suggest their roles as effective immunometric indicators.

PMID- 16981648
TI  - Prevalence of antibodies reactive to pathogenic and nonpathogenic bacteria in
      preimmune serum of New Zealand white rabbits.
AB  - Polyclonal antibodies are typically produced in rabbits. The rabbit's health
      plays an important role in the quality of antibodies produced. Therefore,
      recommendations have been made by organizations on which bacteria and how
      frequently to test rabbit colonies. Since it is well known that rabbits may
      contain cross-reactive antibodies in their preimmune serum, it is common to test
      the rabbits for reactivity prior to immunization. Here preimmune sera from 19
      different rabbits were tested with ELISA against 27 pathogenic and nonpathogenic
      bacterial cultures. ELISA results showed that Salmonella enterica serovar
      Typhimurium and Bacillus cereus AS4-12 had the highest average absorbance values
      (0.60 and 0.54, respectively) and the most preimmune serum samples testing
      positive was 17. Pseudomonas putrefaciens and B. subtilis had the lowest
      absorbance values (< 0.1) and did not test positive in any of the preimmune serum
      samples. Fourteen of the 27 cultures showed positive reactions with 50% or more
      of the preimmune serum samples tested. Fifty-three percent of the rabbit
      preimmune sera showed positive reactions with 10 or more bacterial cultures. In
      Western blot analyses, selected serum samples showing the highest ELISA values
      reacted with bands in the 97, 36, and 29 kDa regions or with bands in the 63 kDa
      and 32 kDa regions. Data suggest that the presence of cross-reactive antibodies
      in the preimmune serum is a common problem amongst the samples tested. Extensive
      preimmune serum testing should be implemented when polyclonal antibodies are
      intended for diagnostic testing.

PMID- 16981649
TI  - Application of Evidence Investigator for the simultaneous measurement of soluble
      adhesion molecules: L-, P-, E- selectins, VCAM-1, ICAM-1 in a biochip platform.
AB  - The semiautomated Evidence Investigator has been applied to the simultaneous
      specific measurement of soluble adhesion molecules: L-, P-, E- selectins, VCAM-1,
      ICAM-1 using a reduced volume of sample. The biochip is the solid support and
      vessel where the sandwich immunoassay takes place. Signal detection, imaging,
      data processing, and storage are fully automated. Calibration curves are
      generated simultaneously for each analyte, with automatic validation against
      supplied calibration data. These curves are used for the calculation of the
      concentrations in multi-analyte controls and human serum samples. Data from the
      evaluation parameters assessed indicate suitability of the Evidence Investigator
      system for the application.

PMID- 16981650
TI  - [Embryology and growth of the skull].

PMID- 16981651
TI  - [Movement of bone at the base and dysmorphogenesis of the skull].

PMID- 16981652
TI  - [Positional plagiocephaly: the place of cranial orthotics].

PMID- 16981653
TI  - [Craniosynostosis: physiopathology].

PMID- 16981654
TI  - [Classification of craniosynostosis].

PMID- 16981655
TI  - [Etiology of craniosynostosis].

PMID- 16981656
TI  - [Diagnosis of craniosynostosis].

PMID- 16981657
TI  - [Prenatal diagnosis of craniosynostosis].

PMID- 16981658
TI  - [Functional retardation in craniosynostosis].

PMID- 16981659
TI  - [The treatment of craniosynostosis: indications and techniques].

PMID- 16981660
TI  - [Anesthesia-resuscitation in the treatment of craniosynostosis].

PMID- 16981661
TI  - [Craniosynostosis: functional and morphologic postoperative results].

PMID- 16981662
TI  - Clinical use of genomics in multiple myeloma.

PMID- 16981663
TI  - Using the HapMap in drug development.

PMID- 16981665
TI  - Sticky platelet syndrome.

PMID- 16981664
TI  - New therapeutic options for renal cell carcinoma.

PMID- 16981666
TI  - Durable remission of intravascular lymphoma with central nervous system
      involvement following chemotherapy and rituximab.

PMID- 16981667
TI  - Long-term results of the MRC AML10 trial.

PMID- 16981668
TI  - CALGB/SWOG C80405: A phase III trial of FOLFIRI or FOLFOX with bevacizumab or
      cetuximab or both for untreated metastatic adenocarcinoma of the colon or rectum.

PMID- 16981669
TI  - Chemotherapy in endometrial cancer.
AB  - Endometrial cancer is a highly curable malignancy when it presents as uterine
      confined disease, but the prognosis for metastatic or recurrent endometrial
      cancer is poor. The median survival of women enrolled in trials for recurrent or
      metastatic endometrial cancer is only approximately 12 months. Hormonal therapy,
      most commonly with progestins, benefits a small group of patients. Cytotoxic
      chemotherapy is indicated as frontline treatment for the majority of women with
      metastatic or recurrent disease. Anthracyclines, platinum compounds, and taxanes
      consistently achieve response rates greater than 20% in single-agent trials of
      chemotherapy-naive patients. Combination chemotherapy typically produces higher
      response rates, although combination regimens have not always improved survival
      historically. Doxorubicin plus cisplatin has been accepted as the Gynecologic
      Oncology Group (GOG) standard regimen based on phase III data. Recently, a COG
      randomized trial compared doxorubicin plus cisplatin to the triplet of
      doxorubicin, cisplatin, and paclitaxel, and it was found that the addition of
      paclitaxel significantly improved response rate, progression-free survival, and
      overall survival. Moreover, chemotherapy has been reported to improve survival
      when

PMID- 16981670
TI  - Trichobezoar: an unusual cause for pancreatitis in a patient with sickle cell
      anemia.

PMID- 16981671
TI  - Amyloid fibrils--common threads in the natural history of proteins.

PMID- 16981673
TI  - Conformational change and assembly through edge beta strands in transthyretin and
      other amyloid proteins.
AB  - Numerous diseases are characterized by the formation of insoluble, amyloid
      protein fibrils. Intensive investigations are beginning to unravel the detailed
      molecular and structural principles that underlie the spontaneous formation of
      these fibrils. The amyloid protein transthyretin serves as an excellent system
      for dissecting the conformational changes and ensuing subunit-subunit
      associations that lead to amyloid. One working model for tranthyretin amyloid
      involves the exposure of an "unprotected" edge beta strand, followed by symmetric
      assembly of subunits to give head-to-head and tail-to-tail protofibrils. The
      models and principles emerging from studies on transthyretin lead to connections
      to other amyloid systems.

PMID- 16981672
TI  - The structural biology of protein aggregation diseases: Fundamental questions and
      some answers.
AB  - Amyloid fibrils are found in association with at least two dozen fatal diseases.
      The tendency of numerous proteins to convert into amyloid-like fibrils poses
      fundamental questions for structural biology and for protein science in general.
      Among these are the following: What is the structure of the cross-beta spine,
      common to amyloid-like fibrils? Is there a sequence signature for proteins that
      form amyloid-like fibrils? What is the nature of the structural conversion from
      native to amyloid states, and do fibril-forming proteins have two distinct stable
      states, the native state and the amyloid state? What is the basis of protein
      complementarity, in which a protein chain can bind to itself? We offer tentative
      answers here, based on our own recent structural studies.

PMID- 16981674
TI  - Hydrogen/deuterium exchange mass spectrometry--a window into amyloid structure.
AB  - The beta-sheet network of the amyloid fibril is a dominant structural feature of
      this class of protein structures. An attractive way to view the protein
      misfolding events that lead to the formation of fibrils and other aggregates is
      to consider how native protein secondary structure rearranges to yield the H
      bonding relationships within the aggregate structure. We describe here the
      application of hydrogen-deuterium exchange mass spectrometry (HX-MS) methods to
      probe the secondary structure of protein aggregates. This includes exploration of
      the structures of monomers, protofibrils, and fibrils, the structural
      relationships among these states, the energetic contribution of H-bonding to
      fibril stability, and the plasticity of the H-bond network.

PMID- 16981675
TI  - Alpha-sheet: The toxic conformer in amyloid diseases?
AB  - A novel secondary structure, the alpha-sheet, was identified through molecular
      dynamics (MD) simulations of various proteins associated with amyloid diseases
      under amyloidogenic conditions. The structure was first predicted by Pauling and
      Corey, and it has been directly observed in crystal structures of "nonnatural
      peptides". There are occurrences of alpha-strands and alpha-sheets in the Protein
      Data Bank, but they are rare. We propose that alpha-sheet is formed during the
      conformational changes associated with amyloidosis and that it may represent the
      toxic conformer. Here, structural properties of the alpha-sheet, background
      information, and experimental support for this novel structure are presented.
      Finally we speculate about the possible role of this conformation in disease.

PMID- 16981676
TI  - Normal and aberrant biological self-assembly: Insights from studies of human
      lysozyme and its amyloidogenic variants.
AB  - Studies of lysozyme have played a major role over several decades in defining the
      general principles underlying protein structure, folding, and stability.
      Following the discovery some 10 years ago that two mutational variants of
      lysozyme are associated with systemic amyloidosis, these studies have been
      extended to investigate the mechanism of amyloid fibril formation. This Account
      describes our present knowledge of lysozyme folding and misfolding, and how the
      latter can give rise to amyloid disease. It also discusses the significance of
      these studies for our general understanding of normal and aberrant protein
      folding in the context of human health and disease.

PMID- 16981677
TI  - Small molecule oxidation products trigger disease-associated protein misfolding.
AB  - Oxidative stress and inflammation are risk factors for both the development of
      alpha-synucleinopathies, such as Parkinson's disease and dementia with Lewy
      bodies, and Alzheimer's disease, the two most common neurodegenerative disorders.
      These diseases are associated with the neurotoxic deposition of misassembled
      alpha-synuclein and amyloid-beta (Abeta) peptides, respectively. Both occur
      sporadically, that is, without detectable disease-related mutations, in the vast
      majority of cases. Small molecule oxidation products, especially secosterols
      derived from cholesterol and 4-hydroxynonenal derived from lipid peroxidation,
      found in afflicted brains, accelerate the misassembly of both Abeta and alpha
      synuclein. This Account explores the mechanism of small molecule oxidation
      product-mediated protein misassembly and possible intervention strategies.

PMID- 16981678
TI  - Sequence and structural determinants of amyloid fibril formation.
AB  - Amyloid fibril formation is a process that represents an essential feature of the
      chemistry of proteins and plays a central role in human pathology and the biology
      of living organisms. In this Account, we shall describe some of the recent
      results on the sequence and structural determinants of protein aggregation. We
      shall describe the factors that govern aggregation of unfolded peptides and
      proteins. We shall then try to summarize the factors that pertain to the
      aggregation of partially structured states and will show that even fully folded
      states of proteins have an ability to aggregate into at least early oligomers
      with no need to undergo substantial conformational changes.

PMID- 16981679
TI  - The aggregation and fibrillation of alpha-synuclein.
AB  - alpha-Synuclein is a small (14 kDa), abundant, intrinsically disordered
      presynaptic protein, whose aggregation is believed to be a critical step in
      Parkinson's disease (PD). The kinetics of alpha-synuclein fibrillation are
      consistent with a nucleation-dependent mechanism, in which the critical early
      stage of the structural transformation involves a partially folded intermediate.
      Although the basis for the toxic effects of aggregated alpha-synuclein are
      unknown, it has been proposed that transient oligomers are responsible, possibly
      by forming pores in membranes. In this Account, I discuss our investigations into
      the molecular basis for alpha-synuclein aggregation/fibrillation, including
      factors that either accelerate or inhibit fibrillation, effects of molecular
      crowding, oxidation, point mutations, and lipid membranes, as well as the variety
      of conformational and oligomeric states that alpha-synuclein can adopt. It is
      apparent that neuronal cells must have a very fine balance of factors that
      control the levels and potential aggregation of alpha-synuclein.

PMID- 16981680
TI  - Elucidating amyloid beta-protein folding and assembly: A multidisciplinary
      approach.
AB  - Oligomeric, neurotoxic amyloid protein assemblies are thought to be causative
      agents in Alzheimer's and other neurodegenerative diseases. Development of
      oligomer-specific therapeutic agents requires a mechanistic understanding of the
      oligomerization process. This is a daunting task because amyloidogenic protein
      oligomers often are metastable and comprise structurally heterogeneous
      populations in equilibrium with monomers and fibrils. A single methodological
      approach cannot elucidate the entire protein assembly process. An integrated
      multidisciplinary program is required. We discuss here the synergistic
      application of in hydro, in vacuo, and in silico methods to the study of the
      amyloid beta-protein, the key pathogenetic agent in Alzheimer's disease.

PMID- 16981681
TI  - Prions and transmissible spongiform encephalopathy (TSE) chemotherapeutics: A
      common mechanism for anti-TSE compounds?
AB  - No validated treatments exist for transmissible spongiform encephalopathies (TSEs
      or prion diseases) in humans or livestock. The search for TSE therapeutics is
      complicated by persistent uncertainties about the nature of mammalian prions and
      their pathogenic mechanisms. In pursuit of anti-TSE drugs, we and others have
      focused primarily on blocking conversion of normal prion protein, PrP(C), to the
      TSE-associated isoform, PrP(Sc). Recently developed high-throughput screens have
      hastened the identification of new inhibitors with strong in vivo anti-TSE
      activities such as porphyrins, phthalocyanines, and phosphorthioated
      oligonucleotides. New routes of administration have enhanced beneficial effects
      against established brain infections. Several different classes of TSE inhibitors
      share structural similarities, compete for the same site(s) on PrP(C), and induce
      the clustering and internalization of PrP(C) from the cell surface. These
      activities may represent a common mechanism of action for these anti-TSE
      compounds.

PMID- 16981682
TI  - The emerging principles of mammalian prion propagation and transmissibility
      barriers: Insight from studies in vitro.
AB  - Self-perpetuating conformational conversion of the cellular prion protein PrP(C)
      into the beta-sheet-rich "scrapie" conformer (PrP(Sc)) is believed to be the
      central molecular event in pathogenesis of a group of diseases known as
      transmissible spongiform encephalopathies. Recent advances provide growing
      support for the notion that a misfolded protein alone might act as an infectious
      agent. Furthermore, findings regarding the mechanism of prion protein structural
      rearrangement, the role of folding intermediates in conformational conversion,
      and "conformational adaptability" in the propagation of prion amyloids in vitro
      yield molecular-level insight into such phenomena as inherited prion diseases,
      prion transmission barriers, and prion strains.

PMID- 16981683
TI  - Direct observation of amyloid fibril growth, propagation, and adaptation.
AB  - Amyloid fibrils form through nucleation and growth. To clarify the mechanism
      involved, direct observations of both processes are important. First, seed
      dependent fibril growth of beta2-microglobulin (beta2-m) and amyloid beta peptide
      was visualized in real time at the single fibril level using total internal
      reflection fluorescence microscopy combined with the binding of thioflavin T, an
      amyloid-specific fluorescence dye. Second, using atomic force microscopy,
      ultrasonication-induced formation of beta2-m fibrils was shown, indicating that
      ultrasonication is useful to accelerate the nucleation process. Third, with the
      proteolytic fragment of beta2-m, propagation and a transformation of fibril
      morphology was demonstrated. These direct observations indicate that template
      dependent growth and structural diversity are key factors determining the
      structure and function of amyloid fibrils.

PMID- 16981684
TI  - Kinetics and thermodynamics of amyloid fibril assembly.
AB  - With some exceptions, amyloids appear to be accidental aggregated structures
      whose formation was not selected for in molecular evolution. Despite this,
      amyloid fibrils are in many respects surprisingly well-behaved molecules. For
      example, Huntington's disease-related polyglutamine sequences aggregate via a
      relatively simple nucleated growth polymerization mechanism. In addition, the
      Alzheimer's plaque protein Abeta has been shown to undergo reversible amyloid
      fibril formation to a position of dynamic equilibrium such that reaction
      thermodynamics can be quantified. Studies of these well-behaved amyloid systems
      are allowing us to peer more deeply into the process and products of off-pathway
      misfolding and aggregation.

PMID- 16981685
TI  - The extended family of neutral sphingomyelinases.
AB  - The neutral sphingomyelinases (N-SMases) are considered major candidates for
      mediating the stress-induced production of ceramide, and N-SMase activity has
      been identified, characterized, and cloned from bacteria, yeast, and mammalian
      cells. Although the level of identity between these enzymes is low, a number of
      key residues thought to be involved in metal binding and catalysis are conserved.
      This has led to the suggestion of a common catalytic mechanism, and thus, these
      enzymes are considered to form an extended family of N-SMases. Despite
      considerable research into N-SMase activity in cell culture and various tissues,
      the lack, until recently, of molecular identification of specific N-SMase enzymes
      had precluded specific insights into the regulation, physiological, and
      pathological roles of these proteins. In this review, we summarize, for the first
      time, current knowledge of the N-SMase family, focusing on cloned members from
      bacteria, yeast, and mammalian cells. We also briefly consider the major future
      directions for N-SMase research which promises highly significant and specific
      insight into sphingolipid-mediated functions.

PMID- 16981686
TI  - Implications for viral capsid assembly from crystal structures of HIV-1 Gag(1
      278) and CA(N)(133-278).
AB  - Gag, the major structural protein of retroviruses such as HIV-1, comprises a
      series of domains connected by flexible linkers. These domains drive viral
      assembly by mediating multiple interactions between adjacent Gag molecules and by
      binding to viral genomic RNA and host cell membranes. Upon viral budding, Gag is
      processed by the viral protease to liberate distinct domains as separate
      proteins. The first two regions of Gag are MA, a membrane-binding module, and CA,
      which is a two-domain protein that makes important Gag-Gag interactions, forms
      the cone-shaped outer shell of the core (the capsid) in the mature HIV-1
      particle, and makes an important interaction with the cellular protein
      cyclophilin A (CypA). Here, we report crystal structures of the mature CA N
      terminal domain (CA(N)(133-278)) and a MA-CA(N) fusion (Gag(1-278)) at
      resolutions/R(free) values of 1.9 A/25.7% and 2.2 A/25.8%, respectively.
      Consistent with earlier studies, a comparison of these structures indicates that
      processing at the MA-CA junction causes CA to adopt an N-terminal beta-hairpin
      conformation that seems to be required for capsid morphology and viral
      infectivity. In contrast with an NMR study (Tang, C., et al. (2002) Nat. Struct.
      Biol. 9, 537-543), structural overlap reveals only small relative displacements
      for helix 6, which is located between the beta-hairpin and the CypA-binding loop.
      These observations argue against the proposal that CypA binding is coupled with
      beta-hairpin formation and support an earlier surface plasmon resonance study
      (Yoo, S., et al. (1997) J. Mol. Biol. 269, 780-795), which concluded that beta
      hairpin formation and CypA-binding are energetically independent events.

PMID- 16981687
TI  - Endocannabinoid metabolism in the absence of fatty acid amide hydrolase (FAAH):
      discovery of phosphorylcholine derivatives of N-acyl ethanolamines.
AB  - Lipid transmitters are tightly regulated by a balance of biosynthetic and
      degradative enzymes. Termination of the activity of the N-acyl ethanolamine (NAE)
      class of lipid-signaling molecules, including the endocannabinoid anandamide
      (AEA), is principally mediated by the integral membrane enzyme fatty acid amide
      hydrolase (FAAH) in vivo. FAAH(-/-) mice are highly sensitized to the
      pharmacological effects of AEA; however, these animals eventually recover from
      AEA treatment, implying the existence of alternative routes for NAE metabolism.
      Here, we have pursued the characterization of these pathways by profiling the
      metabolome of FAAH(-/-) mice treated with AEA. Multiple AEA-induced metabolites
      were observed in brains from FAAH(-/-) mice, including a major product with a
      mass shift of +165 Da (m/z 513). The structure of this product was determined to
      be O-phosphorylcholine (PC)-AEA. Analysis of untreated mice identified PC-NAEs as
      endogenous constituents of the central nervous system (CNS) that were highly
      elevated in FAAH(-/-) animals. PC-NAEs were very poor substrates for FAAH;
      however, a vanadate-sensitive enzymatic activity was detected in brain membranes
      that converted PC-NAEs back to their parent NAEs. The choline-specific
      phosphodiesterase NPP6 was identified as a candidate enzyme responsible for this
      activity. These data indicate the presence of a complete metabolic pathway for
      the production and degradation of PC-NAEs in the CNS that constitutes an
      alternative route for endocannabinoid metabolism.

PMID- 16981688
TI  - Structure of coenzyme A-disulfide reductase from Staphylococcus aureus at 1.54 A
      resolution.
AB  - Coenzyme A (CoASH) replaces glutathione as the major low molecular weight thiol
      in Staphylococcus aureus; it is maintained in the reduced state by coenzyme A
      disulfide reductase (CoADR), a homodimeric enzyme similar to NADH peroxidase but
      containing a novel Cys43-SSCoA redox center. The crystal structure of S. aureus
      CoADR has been solved using multiwavelength anomalous dispersion data and refined
      at a resolution of 1.54 A. The resulting electron density maps define the Cys43
      SSCoA disulfide conformation, with Cys43-S(gamma) located at the flavin si face,
      3.2 A from FAD-C4aF, and the CoAS- moiety lying in an extended conformation
      within a cleft at the dimer interface. A well-ordered chloride ion is positioned
      adjacent to the Cys43-SSCoA disulfide and receives a hydrogen bond from Tyr361'
      OH of the complementary subunit, suggesting a role for Tyr361' as an acid-base
      catalyst during the reduction of CoAS-disulfide. Tyr419'-OH is located 3.2 A from
      Tyr361'-OH as well and, based on its conservation in known functional CoADRs,
      also appears to be important for activity. Identification of residues involved in
      recognition of the CoAS-disulfide substrate and in formation and stabilization of
      the Cys43-SSCoA redox center has allowed development of a CoAS-binding motif.
      Bioinformatics analyses indicate that CoADR enzymes are broadly distributed in
      both bacterial and archaeal kingdoms, suggesting an even broader significance for
      the CoASH/CoAS-disulfide redox system in prokaryotic thiol/disulfide homeostasis.

PMID- 16981689
TI  - X-ray, NMR, and mutational studies of the catalytic cycle of the GDP-mannose
      mannosyl hydrolase reaction.
AB  - GDP-mannose hydrolase catalyzes the hydrolysis with inversion of GDP-alpha-D
      hexose to GDP and beta-D-hexose by nucleophilic substitution by water at C1 of
      the sugar. Two new crystal structures (free enzyme and enzyme-substrate complex),
      NMR, and site-directed mutagenesis data, combined with the structure of the
      enzyme-product complex reported earlier, suggest a four-stage catalytic cycle. An
      important loop (L6, residues 119-125) contains a ligand to the essential Mg2+
      (Gln-123), the catalytic base (His-124), and three anionic residues. This loop is
      not ordered in the X-ray structure of the free enzyme due to dynamic disorder, as
      indicated by the two-dimensional 1H-15N HMQC spectrum, which shows selective
      exchange broadening of the imidazole nitrogen resonances of His-124 (k(ex) = 6.6
      x 10(4) s(-1)). The structure of the enzyme-Mg2+-GDP-mannose substrate complex of
      the less active Y103F mutant shows loop L6 in an open conformation, while the
      structure of the enzyme-Mg2+-GDP product complex showed loop L6 in a closed,
      "active" conformation. 1H-15N HMQC spectra show the imidazole N epsilon of His
      124 to be unprotonated, appropriate for general base catalysis. Substituting Mg2+
      with the more electrophilic metal ions Mn2+ or Co2+ decreases the pKa in the pH
      versus kcat rate profiles, showing that deprotonation of a metal-bound water is
      partially rate-limiting. The H124Q mutation, which decreases kcat 10(3.4)-fold
      and largely abolishes its pH dependence, is rescued by the Y103F mutation, which
      increases kcat 23-fold and restores its pH dependence. The structural basis of
      the rescue is the fact that the Y103F mutation shifts the conformational
      equilibrium to the open form moving loop L6 out of the active site, thus
      permitting direct access of the specific base hydroxide from the solvent. In the
      proposed dissociative transition state, which occurs in the closed, active
      conformation of the enzyme, the partial negative charge of the GDP leaving group
      is compensated by the Mg2+, and by the closing of loop L2 that brings Arg-37
      closer to the beta-phosphate. The development of a positive charge at mannosyl
      C1, as the oxocarbenium-like transition state is approached, is compensated by
      closing the anionic loop, L6, onto the active site, further stabilizing the
      transition state.

PMID- 16981690
TI  - Channeling in sulfate activating complexes.
AB  - The synthesis of activated sulfate (adenosine 5'-phosphosulfate, APS) and
      inorganic pyrophosphate from ATP and SO4 is remarkably unfavorable: K(eq)
      approximately 10(-8) under presumed, near-physiological conditions. Consequently,
      ATP sulfurylases, which catalyze APS synthesis, suffer approximately 10(8)-fold
      losses in catalytic efficiency in the forward (APS-synthesis) versus reverse
      reaction. Losses of this magnitude place this catalyst at risk of being unable to
      supply its nutrients to the cell in a timely fashion. ATP sulfurylase domains are
      often embedded in multifunctional complexes that are capable of also catalyzing
      the second of two steps in the sulfate activation pathway: the phosphorylation of
      APS to produce PAPS (3'-phosphoadenosine 5'-phosphosulfate). The colocalization
      of these activities in a single scaffold suggests that evolution might have
      worked around the inefficiency problem by fashioning a system capable of
      transferring APS directly between the active sites of the complex, thereby
      avoiding the solution-phase energetics. For these reasons, representatives from
      each of the three types of sulfate activating complex (SAC) [Homo sapiens (type
      I); Mycobacterium tuberculosis (type II); and Rhodobacter sphaeroides (type III)]
      were tested for the ability to channel APS. A channeling assay that optically
      detects solution-phase APS was devised with APS reductase from M. tuberculosis, a
      previously uncharacterized enzyme. Channeling was not detected in two of the
      three types of SAC; however, the type III SAC channels with high efficiency.
      Structural models of type III reveal a 75 A-long channel that interconnects
      active-site pairs in the complex and that opens and closes in response to
      occupancy of those sites.

PMID- 16981691
TI  - Mechanistic study of HCV polymerase inhibitors at individual steps of the
      polymerization reaction.
AB  - Little is known about the mechanism of HCV polymerase-catalyzed nucleotide
      incorporation and the individual steps employed by this enzyme during a catalytic
      cycle. In this paper, we applied various biochemical tools and examined the
      mechanism of polymerase catalysis. We found that formation of a productive RNA
      enzyme complex is the slowest step followed by RNA dissociation and initiation of
      primer strand synthesis. Various groups have reported several classes of small
      molecule inhibitors of hepatitis C virus NS5B polymerase; however, the mechanism
      of inhibition for many of these inhibitors is not clear. We undertook a series of
      detailed mechanistic studies to characterize the mechanisms of inhibition for
      these HCV polymerase inhibitors. We found that the diketoacid derivatives
      competitively bind to the elongation NTP pocket in the active site and inhibit
      both the initiation and elongation steps of polymerization. While both
      benzimidazoles and benzothiadiazines are noncompetitive with respect to the
      active site elongation NTP pocket, benzothiadiazine compounds competitively bind
      to the initiation pocket in the active site and inhibit only the initiation step
      of de novo RNA polymerization. The benzimidazoles bind to the thumb allosteric
      pocket and inhibit the conformational changes during RNA synthesis. We also
      observed a cross interaction between the thumb allosteric pocket and the
      initiation pocket using inhibitor-inhibitor cross competition studies. This
      information will be very important in designing combination therapies using two
      small molecule drugs to treat hepatitis C virus.

PMID- 16981692
TI  - Stability of 100 homo and heterotypic coiled-coil a-a' pairs for ten amino acids
      (A, L, I, V, N, K, S, T, E, and R).
AB  - We present the thermal stability monitored by circular dichroism (CD)
      spectroscopy at 222 nm of 100 heterodimers that contain all possible coiled-coil
      a-a' pairs for 10 amino acids (I, V, L, N, A, K S, T, E, and R). This includes
      the stability of 36 heterodimers for 6 amino acids (I, V, L, N, A, and K)
      previously described and 64 new heterodimers including the 4 amino acids (S, T,
      E, and R). We have calculated a double mutant alanine thermodynamic cycle to
      determine a-a' pair coupling energies to evaluate which a-a' pairs encourage
      specific dimerization partners. The four new homotypic a-a' pairs (T-T, S-S, R-R,
      E-E) are repulsive relative to A-A and have destabilizing coupling energies.
      Among the 90 heterotypic a-a' pairs, the stabilizing coupling energies contain
      lysine or arginine paired with either an aliphatic or a polar amino acid. The
      range in coupling energies for each amino acid reveals its potential to regulate
      dimerization specificity. The a-a' pairs containing isoleucine and asparagine
      have the greatest range in coupling energies and thus contribute dramatically to
      dimerization specificity, which is to encourage homodimerization. In contrast,
      the a-a' pairs containing charged amino acids (K, R, and E) show the least range
      in coupling energies and promiscuously encourage heterodimerization.

PMID- 16981693
TI  - Effects of protein-ligand associations on the subunit interactions of
      phosphofructokinase from B. stearothermophilus.
AB  - Differences between the crystal structures of inhibitor-bound and uninhibited
      forms of phosphofructokinase (PFK) from B. stearothermophilus have led to a
      structural model for allosteric inhibition by phosphoenolpyruvate (PEP) wherein a
      dimer-dimer interface within the tetrameric enzyme undergoes a quaternary shift.
      We have developed a labeling and hybridization technique to generate a tetramer
      with subunits simultaneously containing two different extrinsic fluorophores in
      known subunit orientations. This construct has been utilized in the examination
      of the effects of allosteric ligand and substrate binding on the subunit
      affinities of tetrameric PFK using several biophysical and spectroscopic
      techniques including 2-photon, dual-channel fluorescence correlation spectroscopy
      (FCS). We demonstrate that PEP-binding at the allosteric site is sufficient to
      reduce the affinity of the active site interface from beyond the limits of
      experimental detection to nanomolar affinity, while conversely strengthening the
      interface at which it is bound. The reduced interface affinity is specific to
      inhibitor binding because binding the activator ADP at the same allosteric site
      causes no reduction in subunit affinity. With inhibitor bound, the weakened
      subunit affinity has allowed the kinetics of dimer association to be elucidated.

PMID- 16981694
TI  - Despite having a common P1 Leu, eglin C inhibits alpha-lytic proteinase a million
      fold more strongly than does turkey ovomucoid third domain.
AB  - Results of the inhibition of alpha-lytic proteinase by two standard mechanism
      serine proteinase inhibitors, turkey ovomucoid third domain (OMTKY3) and eglin C,
      and many of their variants are presented. Despite similarities, including an
      identical P1 residue (Leu) in their primary contact regions, OMTKY3 and eglin C
      have vastly different association equilibrium constants toward alpha-lytic
      proteinase, with Ka values of 1.8 x 10(3) and 1.2 x 10(9) M(-1), respectively.
      Although 12 of the 13 serine proteinases tested in our laboratory for inhibition
      by OMTKY3 and eglin C are more strongly inhibited by the latter, the million-fold
      difference observed here with alpha-lytic proteinase is the largest we have seen.
      The million-fold stronger inhibition by eglin C is retained when the Ka values of
      the P1 Gly, Ala, Ser, and Ile variants of OMTKY3 and eglin C are compared.
      Despite the small size of the S1 pocket in alpha-lytic proteinase,
      interscaffolding additivity for OMTKY3 and eglin C holds well for the four P1
      residues tested here. To better understand this difference, we measured Ka values
      for other OMTKY3 variants, including some that had residues elsewhere in their
      contact region that corresponded to those of eglin C. Assuming intrascaffolding
      additivity and using the Ka values obtained for OMTKY3 variants, we designed an
      OMTKY3-based inhibitor of alpha-lytic proteinase that was predicted to inhibit
      10,000-fold more strongly than wild-type OMTKY3. This variant
      (K13A/P14E/L18A/R21T/N36D OMTKY3) was prepared, and its Ka value was measured
      against alpha-lytic proteinase. The measured Ka value was in excellent agreement
      with the predicted one (1.1 x 10(7) and 2.0 x 10(7) M(-1), respectively).
      Computational protein docking results are consistent with the view that the
      backbone conformation of eglin C is not significantly altered in the complex with
      alpha-lytic proteinase. They also show that the strong binding for eglin C
      correlates well with more favorable atomic contact energy and desolvation energy
      contributions as compared to OMTKY3.

PMID- 16981695
TI  - A trimerizing GxxxG motif is uniquely inserted in the severe acute respiratory
      syndrome (SARS) coronavirus spike protein transmembrane domain.
AB  - In an attempt to understand what distinguishes severe acute respiratory syndrome
      (SARS) coronavirus (SCoV) from other members of the coronaviridae, we searched
      for elements that are unique to its proteins and not present in any other family
      member. We identified an insertion of two glycine residues, forming the GxxxG
      motif, in the SCoV spike protein transmembrane domain (TMD), which is not found
      in any other coronavirus. This surprising finding raises an "oligomerization
      riddle": the GxxxG motif is a known dimerization signal, while the SCoV spike
      protein is known to be trimeric. Using an in vivo assay, we found that the SCoV
      spike protein TMD is oligomeric and that this oligomerization is driven by the
      GxxxG motif. We also found that the GxxxG motif contributes toward the
      trimerization of the entire spike protein; in that, mutations in the GxxxG motif
      decrease trimerization of the full-length protein expressed in mammalian cells.
      Using molecular modeling, we show that the SCoV spike protein TMD adopts a
      distinct and unique structure as opposed to all other coronaviruses. In this
      unique structure, the glycine residues of the GxxxG motif are facing each other,
      enhancing helix-helix interactions by allowing for the close positioning of the
      helices. This unique orientation of the glycine residues also stabilizes the
      trimeric bundle during multi-nanosecond molecular dynamics simulation in a
      hydrated lipid bilayer. To the best of our knowledge, this is the first
      demonstration that the GxxxG motif can potentiate other oligomeric forms beside a
      dimer. Finally, according to recent studies, the stabilization of the trimeric
      bundle is linked to a higher fusion activity of the spike protein, and the
      possible influence of the GxxxG motif on this feature is discussed.

PMID- 16981696
TI  - HDV ribozyme activity in monovalent cations.
AB  - Activity of the two ribozymes from hepatitis delta virus in monovalent salts was
      examined and compared to activity in Mg2+. Both ribozymes self-cleaved in high
      concentrations of monovalent cations, and an active site cytosine was required
      for cleavage activity under those conditions. Cleavage rates were 30-50-fold
      higher for reactions in LiCl than for reactions in NaCl or NH4Cl, and a thio
      effect indicated that chemistry was rate-determining for cleavage of the HDV
      genomic ribozyme in LiCl. Still, in LiCl, there was a more than 100-fold increase
      in the rate when MgCl2 was included in the reaction. However, the pH-rate
      profiles for the reactions in LiCl with and without MgCl2 were both bell-shaped
      with the pH optima in the neutral range. These findings support the idea that
      monovalent cations can partially substitute for divalent metal ions in the HDV
      ribozymes, although a divalent metal ion is more effective in supporting
      catalysis. The absence of a dramatic change in the general shape of pH-rate
      profiles in LiCl, relative to the profile for reactions including Mg2+, is in
      contrast to earlier data for the reactions in NaCl and limits our interpretation
      of the specific role played by the divalent metal ion in the catalytic mechanism.

PMID- 16981697
TI  - Activation of the cGMP signaling pathway is essential in delaying oocyte aging in
      diabetes mellitus.
AB  - Uncontrolled diabetes mellitus (DM) adversely affects oocyte maturation and
      embryo development via mechanisms that are yet unclear. Nonetheless, DM may cause
      uncoupling of nitric oxide synthases (NOSs) with reduction in the bioavailability
      of nitric oxide (NO), which is critical to maintain oocyte viability and prevent
      aging. The current study investigates the role of NO-mediated signaling related
      to oocyte aging in diabetic and nondiabetic mice. Age-related alterations in the
      oocytes, including ooplasmic microtubule dynamics (OMD), cortical granule (CG)
      status, and zona pellucida (ZP) hardening as well as the integrity of the
      spindle/chromatin were studied using confocal microscopy. Oocytes obtained from
      diabetic mice exhibited accelerated aging compared to that from nondiabetic mice.
      Moreover, oocytes from diabetic animals were exquisitely sensitive to NOS and
      guanylate cyclase (GC) inhibitors (L-NAME, ODQ), which induced aging and
      relatively resistant to its delay by the cGMP derivative (8-Br-cGMP). Oocytes
      from nondiabetic control mice displayed similar sensitivity to L-NAME in older
      oocytes, although to a significantly lower extent than that of DM (P < 0.04
      0.0001). Despite the differences in response between DM and nonDM mice, the
      activation of cGMP pathway is essential to maintain the integrity of oocytes and
      delay oocyte aging. These findings not only indicate the role of NO signaling in
      the prevention of oocyte aging but also suggest enhanced aging and NO
      insufficiency in oocytes from diabetic mice. A comprehensive model incorporating
      our current findings with NOS, GC, and G kinase cycles is presented.

PMID- 16981698
TI  - GSKIP is homologous to the Axin GSK3beta interaction domain and functions as a
      negative regulator of GSK3beta.
AB  - Although prominent FRAT/GBP exhibits a limited degree of homology to Axin, the
      binding sites on GSK3 for FRAT/GBP and Axin may overlap to prevent the effect of
      FRAT/GBP in stabilizing beta-catenin in the Wnt pathway. Using a yeast two-hybrid
      screen, we identified a novel protein, GSK3beta interaction protein (GSKIP),
      which binds to GSK3beta. We have defined a 25-amino acid region in the C-terminus
      of GSKIP that is highly similar to the GSK3beta interaction domain (GID) of Axin.
      Using an in vitro kinase assay, our results indicate that GSKIP is a good
      GSK3beta substrate, and both the full-length protein and a C-terminal fragment of
      GSKIP can block phosphorylation of primed and nonprimed substrates in different
      fashions. Similar to Axin GID(381-405) and FRATtide, synthesized GSKIPtide is
      also shown to compete with and/or block the phosphorylation of Axin and beta
      catenin by GSK3beta. Furthermore, our data indicate that overexpression of GSKIP
      induces beta-catenin accumulation in the cytoplasm and nucleus as visualized by
      immunofluorescence. A functional assay also demonstrates that GSKIP-transfected
      cells have a significant effect on the transactivity of Tcf-4. Collectively, we
      define GSKIP as a naturally occurring protein that is homologous with the
      GSK3beta interaction domain of Axin and is able to negatively regulate GSK3beta
      of the Wnt signaling pathway.

PMID- 16981699
TI  - Minimal determinants for binding activated G alpha from the structure of a G
      alpha(i1)-peptide dimer.
AB  - G-proteins cycle between an inactive GDP-bound state and an active GTP-bound
      state, serving as molecular switches that coordinate cellular signaling. We
      recently used phage display to identify a series of peptides that bind G alpha
      subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S.,
      Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V.
      J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005)
      Structure 13, 1069-1080]. Here we describe the structural features and functions
      of KB-1753, a peptide that binds selectively to GDP x AlF4(-)- and GTPgammaS
      bound states of G alpha(i) subunits. KB-1753 blocks interaction of G
      alpha(transducin) with its effector, cGMP phosphodiesterase, and inhibits
      transducin-mediated activation of cGMP degradation. Additionally, KB-1753
      interferes with RGS protein binding and resultant GAP activity. A fluorescent KB
      1753 variant was found to act as a sensor for activated G alpha in vitro. The
      crystal structure of KB-1753 bound to G alpha(i1) x GDP x AlF4(-) reveals binding
      to a conserved hydrophobic groove between switch II and alpha3 helices and, along
      with supporting biochemical data and previous structural analyses, supports the
      notion that this is the site of effector interactions for G alpha(i) subunits.

PMID- 16981701
TI  - Backbone dynamics of TEM-1 determined by NMR: evidence for a highly ordered
      protein.
AB  - Backbone dynamics of TEM-1 beta-lactamase (263 amino acids, 28.9 kDa) were
      studied by 15N nuclear magnetic resonance relaxation at 11.7, 14.1, and 18.8 T.
      The high quality of the spectra allowed us to measure the longitudinal relaxation
      rate (R1), the transverse relaxation rate (R2), and the {1H}-15N NOE for up to
      227 of the 250 potentially observable backbone amide groups. The model-free
      formalism was used to determine internal motional parameters using an axially
      anisotropic model. TEM-1 exhibits a small prolate axial anisotropy
      (D(parallel)/D(perpendicular) = 1.23 +/- 0.01) and a global correlation time
      (tau(m)) of 12.41 +/- 0.01 ns. The unusually high average generalized order
      parameter (S2) of 0.90 +/- 0.02 indicates that TEM-1 is one of the most ordered
      proteins studied by liquid-state NMR to date. Although the omega-loop has a high
      degree of order in the picosecond-to-nanosecond time scale (mean S2 value of 0.90
      +/- 0.02), we observed the presence of microsecond-to-millisecond time scale
      motions for this loop, as for the vicinity of the active site. These motions
      could be relevant for the catalytic function of TEM-1. Amide exchange experiments
      were also performed, and several amide groups were not exchanged after 12 days,
      an indication that global motions in TEM-1 are also very limited. Although
      detailed dynamics characterization by NMR cannot be readily applied to TEM-1 in
      the presence of relevant substrates, the unusual picosecond-to-nanosecond
      dynamics behavior of TEM-1 presented here will be essential to the validation and
      improvement of future molecular dynamics simulations of TEM-1 in the presence of
      functionally relevant substrates.

PMID- 16981700
TI  - Proximal influences in two-on-two globins: effect of the Ala69Ser replacement on
      Synechocystis sp. PCC 6803 hemoglobin.
AB  - The cyanobacterium Synechocystis sp. PCC 6803 (S6803) expresses a two-on-two
      globin in which His46 (distal side) and His70 (proximal) function as heme iron
      axial ligands. His46 can be displaced by O2, CO, and CN-, among others, whereas
      His70 is not labile under native conditions. The residue preceding the proximal
      histidine has been implicated in controlling globin axial ligand reactivity; the
      details of the mechanism, however, are not well understood, and little
      information exists for bis-histidyl hexacoordinate proteins. In many vertebrate
      hemoglobins and in the Synechocystis protein, the position is occupied by an
      alanine, whereas, in myoglobins, it is a serine involved in an intricate hydrogen
      bond network. We examined the role of Ala69 in S6803 hemoglobin through the
      effects of an Ala --> Ser replacement. The substitution resulted in minor
      structural perturbations, but the response of the holoprotein to temperature-,
      urea-, and acid-induced denaturation was measurably affected. Enhanced three
      state behavior was manifested in the decoupling of heme binding and secondary
      structure formation. Urea-gradient gel experiments revealed that the stability of
      the apoprotein was unchanged by the replacement and that a slight alteration of
      the folding kinetics occurred in the holoproteins. Cyanide-binding experiments
      were performed to assess trans effects. The apparent rate constant for
      association decreased 2-fold upon Ala69Ser replacement. This deceleration was
      attributed to a change in the lifetime of a state containing a decoordinated
      His46. The results demonstrated that, as in vertebrate globins and leghemoglobin,
      proximal influences operate to determine fundamental dynamic and thermodynamic
      properties of the protein.

PMID- 16981702
TI  - Aspartic acid 405 contributes to the substrate specificity of aminopeptidase B.
AB  - Aminopeptidase B (EC 3.4.11.6, ApB) specifically cleaves in vitro the N-terminal
      Arg or Lys residue from peptides and synthetic derivatives. Ap B was shown to
      have a consensus sequence found in the metallopeptidase family. We determined the
      putative zinc binding residues (His324, His328, and Glu347) and the essential
      Glu325 residue for the enzyme using site-directed mutagenesis (Fukasawa, K. M.,
      et al. (1999) Biochem. J. 339, 497-502). To identify the residues binding to the
      amino-terminal basic amino acid of the substrate, rat cDNA encoding ApB was
      cloned into pGEX-4T-3 so that recombinant protein was expressed as a GST fusion
      protein. Twelve acidic amino acid residues (Glu or Asp) in ApB were replaced with
      a Gln or Asn using site-directed mutagenesis. These mutants were isolated to
      characterize the kinetic parameters of enzyme activity toward Arg-NA and compare
      them to those of the wild-type ApB. The catalytic efficiency (kcat/Km) of the
      mutant D405N was 1.7 x 10(4) M(-1) s(-1), markedly decreased compared with that
      of the wild-type ApB (6.2 x 10(5) M(-1) s(-1)). The replacement of Asp405 with an
      Asn residue resulted in the change of substrate specificity such that the
      specific activity of the mutant D405N toward Lys-NA was twice that toward Arg-NA
      (in the case of wild-type ApB; 0.4). Moreover, when Asp405 was replaced with an
      Ala residue, the kcat/Km ratio was 1000-fold lower than that of the wild-type ApB
      for hydrolysis of Arg-NA; in contrast, in the hydrolysis of Tyr-NA, the kcat/Km
      ratios of the wild-type (1.1 x 10(4) M(-1) s(-1)) and the mutated (8.2 x 10(3) M(
      1) s(-1)) enzymes were similar. Furthermore, the replacement of Asp-405 with a
      Glu residue led to the reduction of the kcat/Km ratio for the hydrolysis of Arg
      NA by a factor of 6 and an increase of that for the hydrolysis of Lys-NA. Then
      the kcat/Km ratio of the D405E mutant for the hydrolysis of Lys-NA was higher
      than that for the hydrolysis of Arg-NA as opposed to that of wild-type ApB. These
      data strongly suggest that the Asp 405 residue is involved in substrate binding
      via an interaction with the P1 amino group of the substrate's side chain.

PMID- 16981703
TI  - Transient kinetic experiments demonstrate the existence of a unique catalytic
      enzyme form in the peptide-stimulated ATPase mechanism of Escherichia coli Lon
      protease.
AB  - Lon is an oligomeric serine protease whose proteolytic activity is mediated by
      ATP hydrolysis. Although each monomeric subunit has an identical sequence, Lon
      contains two types of ATPase sites that hydrolyze ATP at drastically different
      rates. The catalytic low-affinity sites display pre-steady-state burst kinetics
      and hydrolyze ATP prior to peptide cleavage. The high-affinity sites are able to
      hydrolyze ATP at a very slow rate. By utilizing the differing Kd's, the high
      affinity site can be blocked with unlabeled nucleotide while the activity at the
      low-affinity site is monitored. Little kinetic data are available that describe
      microscopic events along the reaction pathway of Lon. In this study we utilize
      MANT-ATP, a fluorescent analogue of ATP, to monitor the rate constants for
      binding of ATP as well as the release of ADP from Escherichia coli Lon protease.
      All of the adenine nucleotides tested bound to Lon on the order of 10(5) M(-1) s(
      1), and the previously proposed conformational change associated with nucleotide
      binding was also detected. On the basis of the data obtained in this study we
      propose that the rate of ADP release is slightly different for the two ATPase
      sites. As the model peptide substrate [S2; YRGITCSGRQK(Bz)] [Thomas-Wohlever, J.,
      and Lee, I. (2002) Biochemistry 41, 9418-9425] or the protein substrate casein
      affects only the steady-state ATPase activity of the low-affinity sites, we
      propose that Lon adopts a different form after its first turnover as an ATP
      dependent protease. Based on the obtained rate constants, a revised kinetic model
      is presented for ATPase activity in Lon protease in both the absence and presence
      of the model peptide substrate (S2).

PMID- 16981704
TI  - The transferable tail: fusion of the N-terminal acidic extension of heparin
      cofactor II to alpha1-proteinase inhibitor M358R specifically increases the rate
      of thrombin inhibition.
AB  - The conversion of the reactive center bond of the serpin alpha1-proteinase
      inhibitor (alpha1-PI, also known as alpha1-antitrypsin) from Met-Ser to Arg-Ser
      decreases the rate at which it inhibits neutrophil elastase and endows it with
      the ability to inhibit thrombin and activated protein C (APC). Another serpin,
      heparin cofactor II (HCII), contains a unique N-terminal extension that binds
      thrombin exosite 1. We fused residues 1-75 of HCII to the N-terminus of alpha1-PI
      M358R, forming an HCII-alpha1-PI chimera (HAPI M358R). It inhibited alpha
      thrombin 21-fold faster than alpha1-PI M358R, with second-order rate constants of
      2.3 x 10(8) M(-1) min(-1) versus 1.1 x 10(7) M(-1) min(-1), respectively. When
      gammaT-thrombin, which lacks an intact exosite 1, was substituted for alpha
      thrombin, the kinetic advantage of HAPI M358R over alpha1-PI M358R was reduced to
      9-fold, whereas APC and trypsin, proteases lacking exosite 1-like regions, were
      inhibited only 1.3- and 2-fold more rapidly by HAPI M358R than by alpha1-PI
      M358R, respectively. Maximal enhancement of alpha1-PI M358R activity required the
      acidic residues found between HCII residues 55 and 75, because no enhancement was
      observed either by fusion of residues 1-54 alone or by fusion of a mutated HCII
      acidic extension in which all Glu and Asp residues between positions 55 and 75
      were neutralized by mutation. Fusing residues 55-75 to alpha1-PI M358R yielded a
      relative rate enhancement of only 6-fold, suggesting a need for the full tail
      region to achieve maximal enhancement. Our results suggest that transfer of the N
      terminal acidic extension of HCII to alpha1-PI M358R enhanced its inhibition of
      thrombin by conferring the ability to bind exosite 1 on HAPI M358R. This
      enhancement may aid in efforts to tailor this inhibitor for therapeutic use.

PMID- 16981705
TI  - Positively charged C-terminal subdomains of EcoRV endonuclease: contributions to
      DNA binding, bending, and cleavage.
AB  - The carboxy-terminal subdomains of the homodimeric EcoRV restriction endonuclease
      each bear a net charge of +4 and are positioned on the inner concave surface of
      the 50 degree DNA bend that is induced by the enzyme. A complete kinetic and
      structural analysis of a truncated EcoRV mutant lacking these domains was
      performed to assess the importance of this diffuse charge in facilitating DNA
      binding, bending, and cleavage. At the level of formation of an enzyme-DNA
      complex, the association rate for the dimeric mutant enzyme was sharply decreased
      by 10(3)-fold, while the equilibrium dissociation constant was weakened by nearly
      10(6)-fold compared with that of wild-type EcoRV. Thus, the C-terminal subdomains
      strongly stabilize the enzyme-DNA ground-state complex in which the DNA is known
      to be bent. Further, the extent of DNA bending as observed by fluorescence
      resonance energy transfer was also significantly decreased. The crystal structure
      of the truncated enzyme bound to DNA and calcium ions at 2.4 A resolution reveals
      that the global fold is preserved and suggests that a divalent metal ion crucial
      to catalysis is destabilized in the active site. This may explain the 100-fold
      decrease in the rate of metal-dependent phosphoryl transfer observed for the
      mutant. These results show that diffuse positive charge associated with the C
      terminal subdomains of EcoRV plays a key role in DNA association, bending, and
      cleavage.

PMID- 16981706
TI  - Exploring the role of the active site cysteine in human muscle creatine kinase.
AB  - All known guanidino kinases contain a conserved cysteine residue that interacts
      with the non-nucleophilic eta1-nitrogen of the guanidino substrate. Site-directed
      mutagenesis studies have shown that this cysteine is important, but not essential
      for activity. In human muscle creatine kinase (HMCK) this residue, Cys283, forms
      part of a conserved cysteine-proline-serine (CPS) motif and has a pKa about 3 pH
      units below that of a regular cysteine residue. Here we employ a computational
      approach to predict the contribution of residues in this motif to the unusually
      low cysteine pKa. We calculate that hydrogen bonds to the hydroxyl and to the
      backbone amide of Ser285 would both contribute approximately 1 pH unit, while the
      presence of Pro284 in the motif lowers the pKa of Cys283 by a further 1.2 pH
      units. Using UV difference spectroscopy the pKa of the active site cysteine in WT
      HMCK and in the P284A, S285A, and C283S/S285C mutants was determined
      experimentally. The pKa values, although consistently about 0.5 pH unit lower,
      were in broad agreement with those predicted. The effect of each of these
      mutations on the pH-rate profile was also examined. The results show conclusively
      that, contrary to a previous report (Wang et al. (2001) Biochemistry 40, 11698
      11705), Cys283 is not responsible for the pKa of 5.4 observed in the WT
      V/K(creatine) pH profile. Finally we use molecular dynamics simulations to
      demonstrate that, in order to maintain the linear alignment necessary for
      associative inline transfer of a phosphoryl group, Cys283 needs to be ionized.

PMID- 16981707
TI  - Biosynthesis of fosfomycin, re-examination and re-confirmation of a unique Fe(II)
      and NAD(P)H-dependent epoxidation reaction.
AB  - (S)-2-Hydroxypropylphosphonic acid epoxidase (HppE) catalyzes the epoxide ring
      closure of (S)-HPP to form fosfomycin, a clinically useful antibiotic. Early
      investigation showed that its activity can be reconstituted with Fe(II), FMN,
      NADH, and O2 and identified HppE as a new type of mononuclear non-heme iron
      dependent oxygenase involving high-valent iron-oxo species in the catalysis.
      However, a recent study showed that the Zn(II)-reconstituted HppE is active, and
      HppE exhibits modest affinity for FMN. Thus, a new mechanism is proposed in which
      the active site-bound Fe2+ or Zn2+ serves as a Lewis acid to activate the 2-OH
      group of (S)-HPP and the epoxide ring is formed by the attack of the 2-OH group
      at C-1 coupled with the transfer of the C-1 hydrogen as a hydride ion to the
      bound FMN. To distinguish between these mechanistic discrepancies, we re-examined
      the bioautography assay, the basis for the alternative mechanism, and showed that
      Zn(II) cannot replace Fe(II) in the HppE reaction and NADH is indispensable.
      Moreover, we demonstrated that the proposed role for FMN as a hydride acceptor is
      inconsistent with the finding that FMN cannot bind to HppE in the presence of
      substrate. In addition, using a newly developed HPLC assay, we showed that
      several non-flavin electron mediators could replace FMN in the HppE-catalyzed
      epoxidation. Taken together, these results do not support the newly proposed
      "nucleophilic displacement-hydride transfer" mechanism but are fully consistent
      with the previously proposed iron-redox mechanism for HppE catalysis, which is
      unique within the mononuclear non-heme iron enzyme superfamily.

PMID- 16981708
TI  - Characterization of the acyl substrate binding pocket of acetyl-CoA synthetase.
AB  - AMP-forming acetyl-CoA synthetase [ACS; acetate:CoA ligase (AMP-forming), EC
      6.2.1.1] catalyzes the activation of acetate to acetyl-CoA in a two-step
      reaction. This enzyme is a member of the adenylate-forming enzyme superfamily
      that includes firefly luciferase, nonribosomal peptide synthetases, and acyl- and
      aryl-CoA synthetases/ligases. Although the structures of several superfamily
      members demonstrate that these enzymes have a similar fold and domain structure,
      the low sequence conservation and diversity of the substrates utilized have
      limited the utility of these structures in understanding substrate binding in
      more distantly related enzymes in this superfamily. The crystal structures of the
      Salmonella enterica ACS and Saccharomyces cerevisiae ACS1 have allowed a directed
      approach to investigating substrate binding and catalysis in ACS. In the S.
      enterica ACS structure, the propyl group of adenosine 5'-propylphosphate, which
      mimics the acyl-adenylate intermediate, lies in a hydrophobic pocket. Modeling of
      the Methanothermobacter thermautotrophicus Z245 ACS (MT-ACS1) on the S.
      cerevisiae ACS structure showed similar active site architecture, and alignment
      of the amino acid sequences of proven ACSs indicates that the four residues that
      compose the putative acetate binding pocket are well conserved. These four
      residues, Ile312, Thr313, Val388, and Trp416 of MT-ACS1, were targeted for
      alteration, and our results support that they do indeed form the acetate binding
      pocket and that alterations at these positions significantly alter the enzyme's
      affinity for acetate as well as the range of acyl substrates that can be
      utilized. In particular, Trp416 appears to be the primary determinant for acyl
      chain length that can be accommodated in the binding site.

PMID- 16981709
TI  - Structure and kinetics of phosphonopyruvate hydrolase from Variovorax sp. Pal2:
      new insight into the divergence of catalysis within the PEP mutase/isocitrate
      lyase superfamily.
AB  - Phosphonopyruvate (P-pyr) hydrolase (PPH), a member of the phosphoenolpyruvate
      (PEP) mutase/isocitrate lyase (PEPM/ICL) superfamily, hydrolyzes P-pyr and shares
      the highest sequence identity and functional similarity with PEPM. Recombinant
      PPH from Variovorax sp. Pal2 was expressed in Escherichia coli and purified to
      homogeneity. Analytical gel filtration indicated that the protein exists in
      solution predominantly as a tetramer. The PPH pH rate profile indicates maximal
      activity over a broad pH range. The steady-state kinetic constants determined for
      a rapid equilibrium ordered kinetic mechanism with Mg2+ binding first (Kd = 140
      +/- 40 microM), are kcat = 105 +/- 2 s(-1) and P-pyr Km = 5 +/- 1 microM. PEP
      (slow substrate kcat = 2 x 10(-4) s(-1)), oxalate, and sulfopyruvate are
      competitive inhibitors with Ki values of 2.0 +/- 0.1 mM, 17 +/- 1 microM, and 210
      +/- 10 microM, respectively. Three PPH crystal structures have been determined,
      that of a ligand-free enzyme, the enzyme bound to Mg2+ and oxalate (inhibitor),
      and the enzyme bound to Mg2+ and P-pyr (substrate). The complex with the
      inhibitor was obtained by cocrystallization, whereas that with the substrate was
      obtained by briefly soaking crystals of the ligand-free enzyme with P-pyr prior
      to flash cooling. The PPH structure resembles that of the other members of the
      PEPM/ICL superfamily and is most similar to the functionally related enzyme,
      PEPM. Each monomer of the dimer of dimers exhibits an (alpha/beta)8 barrel fold
      with the eighth helix swapped between two molecules of the dimer. Both P-pyr and
      oxalate are anchored to the active site by Mg2+. The loop capping the active site
      is disordered in all three structures, in contrast to PEPM, where the equivalent
      loop adopts an open or disordered conformation in the unbound state but
      sequesters the inhibitor from solvent in the bound state. Crystal packing may
      have favored the open conformation of PPH even when the enzyme was cocrystallized
      with the oxalate inhibitor. Structure alignment of PPH with other superfamily
      members revealed two pairs of invariant or conservatively replaced residues that
      anchor the flexible gating loop. The proposed PPH catalytic mechanism is
      analogous to that of PEPM but includes activation of a water nucleophile with the
      loop Thr118 residue.

PMID- 16981710
TI  - Quantitative analysis of binding of single-stranded DNA by Escherichia coli DnaB
      helicase and the DnaB x DnaC complex.
AB  - DnaB helicase is responsible for unwinding duplex DNA during chromosomal DNA
      replication and is an essential component of the DNA replication apparatus in
      Escherichia coli. We have analyzed the mechanism of binding of single-stranded
      DNA (ssDNA) by the DnaB x DnaC complex and DnaB helicase. Binding of ssDNA to
      DnaB helicase was significantly modulated by nucleotide cofactors, and the
      modulation was distinctly different for its complex with DnaC. DnaB helicase
      bound ssDNA with a high affinity [Kd = (5.09 +/- 0.32) x 10(-8) M] only in the
      presence of ATPgammaS, a nonhydrolyzable analogue of ATP, but not other
      nucleotides. The binding was sensitive to ionic strength but not to changes in
      temperature in the range of 30-37 degrees C. On the other hand, ssDNA binding in
      the presence of ADP was weaker than that observed with ATPgammaS, and the binding
      was insensitive to ionic strength. DnaC protein hexamerizes to form a 1:1 complex
      with the DnaB hexamer and loads it onto the ssDNA by forming a DnaB6 x DnaC6
      dodecameric complex. Our results demonstrate that the DnaB6 x DnaC6 complex bound
      ssDNA with a high affinity [Kd = (6.26 +/- 0.65) x 10(-8) M] in the presence of
      ATP, unlike the DnaB hexamer. In the presence of ATPgammaS or ADP, binding of
      ssDNA by the DnaB6 x DnaC6 complex was a lower-affinity process. In summary, our
      results suggest that in the presence of ATP in vivo, the DnaB6 x DnaC6 complex
      should be more efficient in binding DNA as well as in loading DnaB onto the ssDNA
      than DnaB helicase itself.

PMID- 16981711
TI  - Detergent-mediated phospholipidation of plasma lipoproteins increases HDL
      cholesterophilicity and cholesterol efflux via SR-BI.
AB  - Cellular cholesterol efflux is an early, obligatory step in reverse cholesterol
      transport, the putative antiatherogenic mechanism by which human plasma high
      density lipoproteins (HDL) transport cholesterol from peripheral tissue to the
      liver for recycling or disposal. HDL-phospholipid content is the essential
      cholesterol-binding component of lipoproteins and therefore a major determinant
      of cholesterol efflux. Thus, increased phospholipidation of lipoproteins,
      particularly HDL, is one strategy for increasing cholesterol efflux. This study
      validates a simple, new detergent perturbation method for the phospholipidation
      of plasma lipoproteins; we have quantified the cholesterophilicity of human
      plasma lipoproteins and the effects of lipoprotein phospholipidation on
      cholesterophilicity and cellular cholesterol efflux mediated by the class B type
      I scavenger receptor (SR-BI). We determined that low-density lipoproteins (LDL)
      are more cholesterophilic than HDL and that LDL has a higher affinity for
      phospholipids than HDL whereas HDL has a higher phospholipid capacity than LDL.
      Phospholipidation of total human plasma lipoproteins enhances cholesterol efflux,
      an effect that occurs largely through the preferential phospholipidation of HDL.
      We conclude that increasing HDL phospholipid increases its cholesterophilicity,
      thereby making it a better acceptor of cellular cholesterol efflux.
      Phospholipidation of lipoproteins by detergent perturbation is a simple way to
      increase HDL cholesterophilicity and cholesterol efflux in a way that may be
      clinically useful.

PMID- 16981712
TI  - Conformational properties of the SDS-bound state of alpha-synuclein probed by
      limited proteolysis: unexpected rigidity of the acidic C-terminal tail.
AB  - Alpha-synuclein (alpha-syn) is a "natively unfolded" protein constituting the
      major component of intracellular inclusions in several neurodegenerative
      disorders. Here, we describe proteolysis experiments conducted on human alpha-syn
      in the presence of SDS micelles. Our aim was to unravel molecular features of
      micelle-bound alpha-syn using the limited proteolysis approach. The nonspecific
      proteases thermolysin and proteinase K, as well as the Glu-specific V8-protease,
      were used as proteolytic probes. While alpha-syn at neutral pH is easily degraded
      to a variety of relatively small fragments, in the presence of 10 mM SDS the
      proteolysis of the protein is rather selective. Complementary fragments 1-111 and
      112-140, 1-113 and 114-140, and 1-123 and 124-140 are obtained when thermolysin,
      proteinase K, and V8 protease, respectively, are used. These results are in line
      with a conformational model of alpha-syn in which it acquires a folded helical
      structure in the N-terminal region in its membrane-bound state. At the same time,
      they indicate that the C-terminal portion of the molecule is rather rigid, as
      seen in its relative resistance to extensive proteolytic degradation. It is
      likely that, under the specific experimental conditions of proteolysis in the
      presence of SDS, the negatively charged C-terminal region can be rigidified by
      binding a calcium ion, as shown before with intact alpha-syn. In this study, some
      evidence of calcium binding properties of isolated C-terminal fragments 112-140,
      114-140, and 124-140 was obtained by mass spectrometry measurements, since
      molecular masses for calcium-loaded fragments were obtained. Our results indicate
      that the C-terminal portion of the membrane-bound alpha-syn is quite rigid and
      structured, at variance from current models of the membrane-bound protein deduced
      mostly from NMR. Considering that the aggregation process of alpha-syn is
      modulated by its C-terminal tail, the results of this study may provide useful
      insights into the behavior of alpha-syn in a membrane-mimetic environment.

PMID- 16981713
TI  - Single chain Fv antibodies against the 25-35 Abeta fragment inhibit aggregation
      and toxicity of Abeta42.
AB  - Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta
      (Abeta) protein in the brain. Immunization studies have demonstrated that anti
      Abeta antibodies reduce Abeta deposition and improve clinical symptoms seen in
      AD. However, conventional antibody-based therapies risk an inflammatory response
      that can result in meningoencephalitis and cerebral hemorrhage. Here we report on
      the development of human-based single chain variable domain antibody fragments
      (scFvs) directed against the Abeta 25-35 region as potential therapeutics for AD
      that do not risk an inflammatory response. The 25-35 region of Abeta represents a
      promising therapeutic target since it promotes aggregation and is highly toxic.
      Two scFvs with differing affinities for Abeta were studied, and both inhibited
      aggregation of Abeta42 as determined by thioflavin T binding assay and atomic
      force microscopy analysis and blocked Abeta-induced toxicity toward human
      neuroblastoma SH-SY5Y cells as determined by MTT and LDH release assays. These
      results provide additional evidence that scFvs against Abeta provide an
      attractive alternative to more conventional antibody-based therapeutics for
      controlling aggregation and toxicity of Abeta.

PMID- 16981714
TI  - Structure and function of the long pentraxin PTX3 glycosidic moiety: fine-tuning
      of the interaction with C1q and complement activation.
AB  - The prototypic long pentraxin PTX3 is a unique fluid-phase pattern recognition
      receptor that plays a nonredundant role in innate immunity and female fertility.
      The PTX3 C-terminal domain is required for C1q recognition and complement
      activation and contains a single N-glycosylation site on Asn 220. In the present
      study, we characterized the structure of the human PTX3 glycosidic moiety and
      investigated its relevance in C1q interaction and activation of the complement
      classical pathway. By specific endo and exoglycosidases digestion and direct mass
      spectrometric analysis, we found that both recombinant and naturally occurring
      PTX3 were N-linked to fucosylated and sialylated complex-type sugars.
      Interestingly, glycans showed heterogeneity mainly in the relative amount of bi,
      tri, and tetrantennary structures depending on the cell type and inflammatory
      stimulus. Enzymatic removal of sialic acid or the entire glycosidic moiety
      equally enhanced PTX3 binding to C1q compared to that in the native protein, thus
      indicating that glycosylation substantially contributes to modulate PTX3/C1q
      interaction and that sialic acid is the main determinant of this contribution.
      BIAcore kinetic measurements returned decreasing K(off) values as sugars were
      removed, pointing to a stabilization of the PTX3/C1q complex. No major
      rearrangement of PTX3 quaternary structure was observed after desialylation or
      deglycosylation as established by size exclusion chromatography. Consistent with
      C1q binding, PTX3 desialylation enhanced the activation of the classical
      complement pathway, as assessed by C4 and C3 deposition. In conclusion, our
      results provided evidence of an involvement of the PTX3 sugar moiety in C1q
      recognition and complement activation.

PMID- 16981715
TI  - Mechanism of the highly efficient quenching of tryptophan fluorescence in human
      gammaD-crystallin.
AB  - Quenching of the fluorescence of buried tryptophans (Trps) is an important
      reporter of protein conformation. Human gammaD-crystallin (HgammaD-Crys) is a
      very stable eye lens protein that must remain soluble and folded throughout the
      human lifetime. Aggregation of non-native or covalently damaged HgammaD-Crys is
      associated with the prevalent eye disease mature-onset cataract. HgammaD-Crys has
      two homologous beta-sheet domains, each containing a pair of highly conserved
      buried tryptophans. The overall fluorescence of the Trps is quenched in the
      native state despite the absence of the metal ligands or cofactors. We report the
      results of detailed quantitative measurements of the fluorescence emission
      spectra and the quantum yields of numerous site-directed mutants of HgammaD-Crys.
      From fluorescence of triple Trp to Phe mutants, the homologous pair Trp68 and
      Trp156 were found to be extremely quenched, with quantum yields close to 0.01.
      The homologous pair Trp42 and Trp130 were moderately fluorescent, with quantum
      yields of 0.13 and 0.17, respectively. In an attempt to identify quenching and/or
      electrostatically perturbing residues, a set of 17 candidate amino acids around
      Trp68 and Trp156 were substituted with neutral or hydrophobic residues. None of
      these mutants showed significant changes in the fluorescence intensity compared
      to their own background. Hybrid quantum mechanical-molecular mechanical (QM-MM)
      simulations with the four different excited Trps as electron donors strongly
      indicate that electron transfer rates to the amide backbone of Trp68 and Trp156
      are extremely fast relative to those for Trp42 and Trp130. This is in agreement
      with the quantum yields measured experimentally and consistent with the absence
      of a quenching side chain. Efficient electron transfer to the backbone is
      possible for Trp68 and Trp156 because of the net favorable location of several
      charged residues and the orientation of nearby waters, which collectively
      stabilize electron transfer electrostatically. The fluorescence emission spectra
      of single and double Trp to Phe mutants provide strong evidence for energy
      transfer from Trp42 to Trp68 in the N-terminal domain and from Trp130 to Trp156
      in the C-terminal domain. The backbone conformation of tryptophans in HgammaD
      Crys may have evolved in part to enable the lens to become a very effective UV
      filter, while the efficient quenching provides an in situ mechanism to protect
      the tryptophans of the crystallins from photochemical degradation.

PMID- 16981716
TI  - The binding of DYNLL2 to myosin Va requires alternatively spliced exon B and
      stabilizes a portion of the myosin's coiled-coil domain.
AB  - The myosin Va light chain DYNLL2 has been proposed to function as an adaptor to
      link the myosin to certain cargo. Here, we mapped the binding site for DYNLL2
      within the myosin Va heavy chain. Copurification and pull-down experiments showed
      that the heavy chain contains a single DYNLL2 binding site and that this site
      resides within a discontinuity in the myosin's central coiled-coil domain.
      Importantly, exon B, an alternatively spliced, three-amino acid exon, is a part
      of this binding site, and we show in the context of full-length myosin Va that
      this exon is required for DYNLL2-myosin Va interaction. We investigated the
      effect of DYNLL2 binding on the structure of a myosin Va heavy chain fragment
      that contains the DYNLL2 binding site and flanking sequence, only parts of which
      are strongly predicted to form a coiled coil. Circular dichroism measurements
      revealed a DYNLL2-induced change in the secondary structure of this dimeric
      myosin fragment that is consistent with an increase in alpha-helical coiled-coil
      content. Moreover, the binding of DYNLL2 considerably stabilizes this heavy chain
      fragment against thermal denaturation. Analytical ultracentrifugation yielded an
      apparent association constant of approximately 3 x 10(6) M(-1) for the
      interaction of DYNLL2 with the dimeric myosin fragment. Together, these data show
      that alternative splicing of the myosin Va heavy chain controls DYNLL2-myosin Va
      interaction and that DYNLL2 binding alters the structure of a portion of the
      myosin's coiled-coil domain. These results suggest that exon B could have a
      significant impact on the conformation and regulatory folding of native myosin
      Va, as well as on its interaction with certain cargos.

PMID- 16981717
TI  - Anion uptake in halorhodopsin from Natromonas pharaonis studied by FTIR
      spectroscopy: consequences for the anion transport mechanism.
AB  - The uptake of chloride, bromide, iodide, nitrate, and azide by anion-depleted
      blue halorhodopsin from Natronobacterium pharaonis has been followed by FTIR
      difference spectroscopy using an ATR sampling device. The spectra are compared
      with the spectrum of the O intermediate obtained by time-resolved FTIR studies of
      the photocycle. It is demonstrated that anion-free blue halorhodopsin can be
      identified with the O intermediate and, thus, that the decay of O is due to the
      passive uptake of the anion. The great similarity of the anion-binding spectra
      and their identity in the case of the monoatomic anions indicate a rather
      unspecific binding site for the different anions dominated by electrostatic
      interactions. Comparing spectra obtained with 15N nitrate and unlabeled nitrate,
      the NO-stretching bands could be identified. The small splitting and the small IR
      intensity of those bands indicate a rather nonpolar binding site with a rather
      isotropic influence on the nitrate, in contrast to aqueous nitrate. In further
      experiments on the photocycle of blue halorhodopsin, the all-trans --> 13-cis
      isomerization can be clearly identified. Up to 100 micros, the isomerization
      induced structural changes deduced from amide I changes are similar to those
      occurring during the anion-transporting photocycle. Compared to these, the
      molecular changes involved in the release and their reversion during the uptake
      of anions are considerably larger. They can be reached via two pathways: (1) by
      reducing the anion concentration and (2) transiently during the anion
      transporting photocycle with the formation of the precursor of O with O
      conformation. Consequences of the anion transport mechanism are discussed.

PMID- 16981718
TI  - Temperature dependence of nucleotide association and kinetic characterization of
      myo1b.
AB  - Myo1b is a widely expressed myosin-I isoform that concentrates on endosomal and
      ruffling membranes and is thought to play roles in membrane trafficking and
      dynamics. It is one of the best characterized myosin-I isoforms and appears to
      have unique biochemical properties tuned for tension sensing or tension
      maintenance. We determined the key biochemical rate constants that define the
      actomyo1b ATPase cycle at 37 degrees C and measured the temperature dependence of
      ATP binding, ADP release, and the transition from a nucleotide-inaccessible state
      to a nucleotide-accessible state (k(alpha)). The rate of ATP binding is highly
      temperature sensitive, with an Arrhenius activation energy 2-3-fold greater than
      other characterized myosins (e.g., myosin-II and myosin-V). ATP hydrolysis is
      fast, and phosphate release is slow and rate limiting with an actin dependence
      that is nearly identical to the steady-state ATPase parameters (Vmax and
      K(ATPase)). ADP release is not as temperature dependent as ATP binding. The rates
      and temperature dependence of ADP release are similar to k(alpha) suggesting that
      a similar structural change is responsible for both transitions. We calculate a
      duty ratio of 0.08 based on the biochemical kinetics. However, this duty ratio is
      likely to be highly sensitive to strain.

PMID- 16981719
TI  - Identification of the single specific IQ motif of myosin V from which calmodulin
      dissociates in the presence of Ca2+.
AB  - Each heavy chain of dimeric chick brain myosin V (BMV) has a neck domain
      consisting of six IQ motifs with different amino acid sequences. The six IQ
      motifs form binding sites for five calmodulin (CaM) molecules and one essential
      light chain (either 17 or 23 kDa). When the calcium concentration is high, a
      small fraction of the 10 total CaM molecules dissociates from one molecule of
      BMV, resulting in loss of actin-based motor activity. At low Ca2+ concentrations,
      two molecules of exogenous CaM associate with one molecule of CaM-released BMV.
      This suggests that there is a single specific IQ motif responsible for the
      calcium-induced dissociation of CaM. In this study, we identify the specific IQ
      motif to be IQ2, the second IQ motif when counted from the N-terminal end of the
      neck domain. In addition, we showed that the essential light chains do not reside
      on IQ1 and IQ2. These findings were derived from proteolysis of BMV at high Ca2+
      concentrations specifically at the neck region and SDS-PAGE analyses of the
      digests.

PMID- 16981720
TI  - Involvement of insulin-like growth factor type 1 receptor and protein kinase
      Cdelta in bis(maltolato)oxovanadium(IV)-induced phosphorylation of protein kinase
      B in HepG2 cells.
AB  - Vanadium(IV) oxo-bis(maltolato) (BMOV), an organovanadium compound, is a potent
      insulinomimetic agent and improves glucose homeostasis in various models of
      diabetes. We have shown previously that BMOV stimulates the phosphorylation of
      PKB which may contribute as one of the mechanisms for the insulinomimetic effect
      of this compound. However, the upstream mechanism of BMOV-induced PKB
      phosphorylation remains elusive. Therefore, in this study, we examine the
      upstream events leading to BMOV-induced PKB phosphorylation in HepG2 cells. Since
      BMOV is an inhibitor of protein tyrosine phosphatases and through enhanced
      tyrosine phosphorylation may activate various protein tyrosine kinases (PTK), we
      have investigated the potential role of different receptor or nonreceptor PTK in
      mediating BMOV-induced PKB phosphorylation. Among several pharmacological
      inhibitors that were tested, only AG1024, a selective inhibitor of IGF-1R-PTK,
      almost completely blocked BMOV-stimulated phosphorylation of PKB. In contrast,
      AG1295 and AG1478, specific inhibitors of PDGFR and EGFR, respectively, were
      unable to block the BMOV response. Moreover, efficient reduction of the level of
      IGF-1R protein expression by antisense oligonucleotides (ASO) attenuated BMOV
      induced PKB phosphorylation. BMOV-induced PKB phosphorylation was associated with
      an increased level of tyrosine phosphorylation of the IRbeta subunit, IGF-1Rbeta
      subunit, IRS-1, and p85alpha subunit of PI3-kinase. However, this response was
      independent of IR-PTK activity because in cells overexpressing a PTK-inactive
      form of IR, insulin response was attenuated while the effect of BMOV remained
      intact. A role of PKC in BMOV-induced response was also tested. Pharmacological
      inhibition with chelerythrine, a nonselective PKC inhibitor, or rottlerin, a
      PKCdelta inhibitor, as well as chronic treatment with PMA attenuated BMOV-induced
      PKB phosphorylation. In contrast, GO6976 and RO31-8220 PKCalpha/beta selective
      inhibitors failed to alter the BMOV effect. Taken together, these data suggest
      that IGF-1R and PKCdelta are required to stimulate PKB phosphorylation in
      response to BMOV in HepG2 cells and provide new insights into the molecular
      mechanism by which this compound exerts its insulinomimetic effects.

PMID- 16981721
TI  - Influence of differential stability of G protein betagamma dimers containing the
      gamma11 subunit on functional activity at the M1 muscarinic receptor, A1
      adenosine receptor, and phospholipase C-beta.
AB  - Ggamma11 is an unusual guanine nucleotide-binding regulatory protein (G protein)
      subunit. To study the effect of different Gbeta-binding partners on gamma11
      function, four recombinant betagamma dimers, beta1gamma2, beta4gamma2,
      beta1gamma11, and beta4gamma11, were characterized in a receptor reconstitution
      assay with the G(q)-linked M1 muscarinic and the G(i1)-linked A1 adenosine
      receptors. The beta4gamma11 dimer was up to 30-fold less efficient than
      beta4gamma2 at promoting agonist-dependent binding of [35S]GTPgammaS to either
      alpha(q) or alpha(i1). Using a competition assay to measure relative affinities
      of purified betagamma dimers for alpha, the beta4gamma11 dimer had a 15-fold
      lower affinity for G(i1) alpha than beta4gamma2. Chromatographic characterization
      of the beta4gamma11 dimer revealed that the betagamma is stable in a
      heterotrimeric complex with G(i1) alpha; however, upon activation of alpha with
      MgCl2 and GTPgammaS under nondenaturing conditions, the beta4 and gamma11
      subunits dissociate. Activation of purified G(i1) alpha:beta4gamma11 with
      Mg+2/GTPgammaS following reconstitution into lipid vesicles and incubation with
      phospholipase C (PLC)-beta resulted in stimulation of PLC-beta activity; however,
      when this activation preceded reconstitution into vesicles, PLC-beta activity was
      markedly diminished. In a membrane coupling assay designed to measure the ability
      of G protein to promote a high-affinity agonist-binding conformation of the A1
      adenosine receptor, beta4gamma11 was as effective as beta4gamma2 when coexpressed
      with G(i1) alpha and receptor. However, G(i1) alpha:beta4gamma11-induced high
      affinity binding was up to 20-fold more sensitive to GTPgammaS than G(i1)
      alpha:beta4gamma2-induced high-affinity binding. These results suggest that the
      stability of the beta4gamma11 dimer can modulate G protein activity at the
      receptor and effector.

PMID- 16981722
TI  - On the mechanism of alleviation by phenobarbital of the malfunction of an
      epilepsy-linked GABA(A) receptor.
AB  - A mechanism for the alleviation of the malfunction of a mutated (gamma2(K289M))
      epilepsy-linked gamma-aminobutyric acid (GABA) neurotransmitter receptor by
      phenobarbital is presented. Compared to the wild-type receptor, the GABA-induced
      current is considerably reduced in the mutated (alpha1beta2gamma2(K289M))
      epilepsy-linked GABA(A) receptor [Baulac, S., Huberfeld, G., Gurfinkel-An, I.,
      Mitropoulou, G., Beranger, A., Prud'homme, J. F., Baulac, M., Brice, A.,
      Bruzzone, R., and LeGuer, E. (2001) Nat. Genet. 28, 46-48]. This is due to an
      impaired GABA-induced equilibrium between the closed- and open-channel forms of
      the receptor [Ramakrishnan, L., and Hess, G. P. (2004) Biochemistry 43, 7534
      7540]. We report that a barbiturate anticonvulsant, phenobarbital, alleviates the
      effect of this mutation. Transient kinetic techniques with a millisecond-to
      microsecond time resolution and the wild-type and mutated receptors recombinantly
      expressed in mammalian HEK293T cells were used. The efficacy of phenobarbital in
      potentiating currents elicited by a saturating concentration of GABA is about 3
      times higher for the mutated receptor than for the wild type. The results
      indicate that phenobarbital alleviates the malfunction of the mutated receptor by
      increasing its channel-opening equilibrium constant (phi(-1) = k(op)/k(cl)) by
      about an order of magnitude. Phenobarbital changes the channel-opening rate
      constant (k(op)) by less than 2-fold but decreases the channel-closing rate
      constant (k(cl)) 8-fold. The dissociation constant of GABA is unaffected. The
      experiments also indicate that at saturating concentrations of GABA the mutated
      (gamma2(K289M)) form of the alpha1beta2gamma2 GABA(A) receptor is well suited for
      a rapid and simple screening of positive allosteric modulators of the receptor.

PMID- 16981723
TI  - The mechanism of heme transfer from the cytoplasmic heme binding protein PhuS to
      the delta-regioselective heme oxygenase of Pseudomonas aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa has evolved two outer membrane
      receptor-mediated uptake systems (encoded by the phu and has operons) by which it
      can utilize the hosts heme and hemeproteins as a source of iron. PhuS is a
      cytoplasmic heme binding protein encoded within the phu operon and has previously
      been shown to function in the trafficking of heme to the iron-regulated heme
      oxygenase (pa-HO). While the heme association rate for PhuS was similar to that
      of myoglobin, a markedly higher rate of heme dissociation (approximately 10(5) s(
      1)) was observed, in keeping with a function in heme-trafficking. Additionally,
      the transfer of heme from PhuS to pa-HO was shown to be specific and
      unidirectional when compared to transfer to the non-iron regulated heme oxygenase
      (BphO), in which heme distribution between the two proteins merely reflects their
      relative intrinsic affinities for heme. Furthermore, the rate of transfer of heme
      from holo-PhuS to pa-HO of 0.11 +/- 0.01 s(-1) is 30-fold faster than that to apo
      myoglobin, despite the significant higher binding affinity of apo-myoglobin for
      heme (kH = 1.3 x 10(-8) microM) than that of PhuS (0.2 microM). This data
      suggests that heme transfer to pa-HO is independent of heme affinity and is
      consistent with temperature dependence studies which indicate the reaction is
      driven by a negative entropic contribution, typical of an ordered transition
      state, and supports the notion that heme transfer from PhuS to pa-HO is mediated
      via a specific protein-protein interaction. In addition, pH studies, and
      reactions conducted in the presence of cyanide, suggest the involvement of spin
      transition during the heme transfer process, whereby the heme undergoes spin
      change from 6-c LS to 6-c HS either in PhuS or pa-HO. On the basis of the
      magnitudes of the activation parameters obtained in the presence of cyanide,
      whereby both complexes are maintained in a 6-c LS state, and the biphasic
      kinetics of heme transfer from holo-PhuS to pa-HO-wt, supports the notion that
      the spin-state crossover occur within holo-PhuS prior to the heme transfer step.
      Alternatively, the lack of the biphasic kinetic with pa-HO-G125V, 6-c LS, and
      with comparable rate of heme transfer as pa-HO is supportive of a mechanism in
      which the spin-change could occur within pa-HO. The present data suggests either
      or both of the two pathways proposed for heme transfer may occur under the
      present experimental conditions. The dissection of which pathway is
      physiologically relevant is the focus of ongoing studies.

PMID- 16981724
TI  - Reaction of adenosylcobalamin-dependent glutamate mutase with 2-thiolglutarate.
AB  - We have investigated the reaction of glutamate mutase with the glutamate
      analogue, 2-thiolglutarate. In the standard assay, 2-thiolglutarate behaves as a
      competitive inhibitor with a Ki of 0.05 mM. However, rather than simply binding
      inertly at the active site, 2-thiolglutarate elicits cobalt-carbon bond homolysis
      and the formation of 5'-deoxyadenosine. The enzyme exhibits a complicated EPR
      spectrum in the presence of 2-thiolglutarate that is markedly different from any
      previously observed with the enzyme. The spectrum was simulated well by assuming
      that it arises from electron-electron spin coupling between a thioglycolyl
      radical and low-spin Co2+ in cob(II)alamin. Analysis of the zero-field splitting
      parameters obtained from the simulations places the organic radical approximately
      10 A from the cobalt and at a tilt angle of approximately 70 degrees to the
      normal of the corrin ring. This orientation is in good agreement with that
      expected from the crystal structure of glutamate mutase complexed with the
      substrate. 2-Thiolglutarate appears to react in a manner analogous to that of
      glutamate by first forming a thiolglutaryl radical at C-4 that then undergoes
      fragmentation to produce acrylate and the sulfur-stabilized thioglycolyl radical.
      The thioglycolyl radical accumulates on the enzyme, suggesting it is too stable
      to undergo further steps in the mechanism at a detectable rate.

PMID- 16981725
TI  - Bias from H2 cleavage to production and coordination changes at the Ni-Fe active
      site in the NAD+-reducing hydrogenase from Ralstonia eutropha.
AB  - The soluble NAD+-reducing Ni-Fe hydrogenase (SH) from Ralstonia eutropha H16 is
      remarkable because it cleaves hydrogen in the presence of dioxygen at a unique Ni
      Fe active site (Burgdorf et al. (2005) J. Am. Chem. Soc. 127, 576). By X-ray
      absorption (XAS), FTIR, and EPR spectroscopy, we monitored the structure and
      oxidation state of its metal centers during H2 turnover. In NADH-activated
      protein, a change occurred from the (CN)O2Ni(II)(mu-S)2Fe(II)(CN)3(CO) site
      dominant in the wild-type SH to a standard-like S2Ni(II)(mu-S)2Fe(II)(CN)2(CO)
      site as the prevailing species in a specific mutant protein, HoxH-H16L. The wild
      type SH primarily was active in H2 cleavage. The nonstandard reaction mechanism
      does not involve stable EPR-detectable trivalent Ni oxidation states, namely, the
      Ni-A,B,C states as observed in standard hydrogenases. In the HoxH-mutant protein
      H16L, H2 oxidation was impaired, but H2 production occurred via a stable Ni-C
      state (Ni(III)-H(-)-Fe(II)), suggesting a reaction sequence similar to that of
      standard hydrogenases. It is proposed that reductive activation by NADH of both
      wild-type and H16L proteins causes the release of an oxygen species from Ni and
      is initiated by electron transfer from a [2Fe-2S] cluster in the HoxU subunit
      that at first becomes reduced by electrons from NADH. Electrons derived from H2
      cleavage, on the other hand, are transferred to NAD+ via a different pathway
      involving a [4Fe-4S] cluster in HoxY, which is reducible only in wild-type SH but
      not in the H16L variant.

PMID- 16981726
TI  - Unfolding of alanine-based peptides using electron spin resonance distance
      measurements.
AB  - We describe a scheme for tagging an alanine-based peptide with a Cu(II) and a
      nitroxide to measure unfolding transitions. The enhancement in longitudinal
      relaxation rate of the nitroxide due to the presence of Cu(II) was measured at
      physiological temperatures by pulsed electron spin resonance (ESR). The change in
      relaxation rate provided the average interspin distance between the Cu(II) and
      the nitroxide. Control experiments on a proline-based peptide verify the
      robustness of the method. The change in interspin distances with temperature for
      the alanine-based peptide is in accord with the change in helicity measured by
      circular dichroism. The data provide an opportunity to examine the unfolding
      process in polyalanine peptides. The distance in the folded state is in
      concordance with molecular dynamics. However, the ESR experiment measures an
      average distance of 17 A in the unfolded state, whereas molecular dynamics
      indicates a distance of 42 A if the unfolded geometry was a polyproline type II
      helix. Therefore, ESR demonstrates that the unfolded state of this alanine-based
      peptide is not an ideal extended polyproline type II helix.

PMID- 16981727
TI  - Ability of viral topoisomerase II to discern the handedness of supercoiled DNA:
      bimodal recognition of DNA geometry by type II enzymes.
AB  - Previous studies with human and bacterial topoisomerases suggest that the type II
      enzyme utilizes two distinct mechanisms to recognize the handedness of DNA
      supercoils. It has been proposed that the ability of some type II enzymes, such
      as human topoisomerase IIalpha and Escherichia coli topoisomerase IV, to
      distinguish supercoil geometry during DNA relaxation is mediated by elements in
      the variable C-terminal domain of the protein. In contrast, the ability of human
      topoisomerase IIalpha and topoisomerase IIbeta to discern the handedness of
      supercoils during DNA cleavage suggests that residues in the conserved N-terminal
      or central domain of the protein are involved in this process. To test this
      hypothesis, the ability of Paramecium bursaria chlorella virus-1 (PBCV-1) and
      chlorella virus Marburg-1 (CVM-1) topoisomerase II to relax and cleave negatively
      and positively supercoiled plasmids was assessed. These enzymes display a high
      degree of sequence identity with the N-terminal and central domains of eukaryotic
      topoisomerase II but naturally lack the C-terminal domain. While PBCV-1 and CVM-1
      topoisomerase II relaxed under- and overwound substrates at similar rates, they
      were able to discern the handedness of supercoils during the cleavage reaction
      and preferentially cut negatively supercoiled DNA. Preferential cleavage was not
      due to a change in site specificity, DNA binding, or religation. These findings
      are consistent with a bimodal recognition of DNA geometry in which topoisomerase
      II uses elements in the C-terminal domain to sense the handedness of supercoils
      during DNA relaxation and elements in the conserved N-terminal or central domain
      during DNA cleavage.

PMID- 16981729
TI  - Bivalent probes of the human multidrug transporter P-glycoprotein.
AB  - A small library of bivalent agents was designed to probe the substrate binding
      sites of the human multidrug transporter P-glycoprotein (P-gp). The bivalent
      agents were composed of two copies of the P-gp substrate emetine, linked by
      tethers of varied composition. An optimum distance between the emetine molecules
      of approximately 10 A was found to be necessary for blocking transport of the
      known fluorescent substrate rhodamine 123. Additionally, it was determined that
      hydrophobic tethers were optimal for bridging the bivalent compounds; hydrophilic
      or cationic moieties within the tether had a detrimental effect on inhibition of
      transport. In addition to acting as probes of P-gp's drug binding sites, these
      agents were also potent inhibitors of P-gp. One agent, EmeC5, had IC50 values of
      2.9 microM for inhibiting transport of rhodamine 123 and approximately 5 nM for
      inhibiting the binding of a known P-gp substrate, [125I]iodoarylazidoprazosin.
      Although EmeC5 is an inhibitor of P-gp and was shown to interact directly with P
      gp in one or more of the substrate binding sites, our data suggest that it is
      either not a P-gp transport substrate itself or a poor one. Most significantly,
      EmeC5 was shown to reverse the MDR phenotype of MCF-7/DX1 cells when co
      administered with a cytotoxic agent, such as doxorubicin.

PMID- 16981728
TI  - Selective deletion of the NH2-terminal variable region of cardiac troponin T in
      ischemia reperfusion by myofibril-associated mu-calpain cleavage.
AB  - The structure of the NH2-terminal region of troponin T (TnT) is hypervariable
      among the muscle type-specific isoforms and is also regulated by alternative RNA
      splicing. This region does not contain binding sites for other thin filament
      proteins, but alteration of its structure affects the Ca2+ regulation of muscle
      contraction. Here we report a truncated cardiac TnT produced during myocardial
      ischemia reperfusion. Amino acid sequencing and protein fragment reconstruction
      determined that it is generated by a posttranslational modification selectively
      removing the NH2-terminal variable region and preserving the conserved core
      structure of TnT. Triton X-100 extraction of cardiac muscle fibers promoted
      production of the NH2-terminal truncated cardiac TnT (cTnT-ND), indicating a
      myofibril-associated proteolytic activity. Mu-calpain is a myofibril-associated
      protease and is known to degrade TnT. Supporting a role of mu-calpain in
      producing cTnT-ND in myocardial ischemia reperfusion, calpain inhibitors
      decreased the level of cTnT-ND in Triton-extracted myofibrils. Mu-calpain
      treatment of the cardiac myofibril and troponin complex specifically reproduced
      cTnT-ND. In contrast, mu-calpain treatment of isolated cardiac TnT resulted in
      nonspecific degradation, suggesting that this structural modification is relevant
      to physiological structures of the myofilament. Triton X-100 treatment of
      transgenic mouse cardiac myofibrils overexpressing fast skeletal muscle TnT
      produced similar NH2-terminal truncations of the endogenous and exogenous TnT,
      despite different amino acid sequences at the cleavage site. With the functional
      consequences of removing the NH2-terminal variable region of TnT, the mu-calpain
      mediated proteolytic modification of TnT may act as an acute mechanism to adjust
      muscle contractility under stress conditions.

PMID- 16981730
TI  - Cavitation as a mechanism of substrate discrimination by adenylosuccinate
      synthetases.
AB  - Adenylosuccinate synthetase catalyzes the first committed step in the de novo
      biosynthesis of AMP, coupling L-aspartate and IMP to form adenylosuccinate. Km
      values of IMP and 2'-deoxy-IMP are nearly identical with each substrate
      supporting comparable maximal velocities. Nonetheless, the Km value for L
      aspartate and the Ki value for hadacidin (a competitive inhibitor with respect to
      L-aspartate) are 29-57-fold lower in the presence of IMP than in the presence of
      2'-deoxy-IMP. Crystal structures of the synthetase ligated with hadacidin, GDP,
      and either 6-phosphoryl-IMP or 2'-deoxy-6-phosphoryl-IMP are identical except for
      the presence of a cavity normally occupied by the 2'-hydroxyl group of IMP. In
      the presence of 6-phosphoryl-IMP and GDP (hadacidin absent), the L-aspartate
      pocket can retain its fully ligated conformation, forming hydrogen bonds between
      the 2'-hydroxyl group of IMP and sequence-invariant residues. In the presence of
      2'-deoxy-6-phosphoryl-IMP and GDP, however, the L-aspartate pocket is poorly
      ordered. The absence of the 2'-hydroxyl group of the deoxyribonucleotide may
      destabilize binding of the ligand to the L-aspartate pocket by disrupting
      hydrogen bonds that maintain a favorable protein conformation and by the
      introduction of a cavity into the fully ligated active site. At an approximate
      energy cost of 2.2 kcal/mol, the unfavorable thermodynamics of cavity formation
      may be the major factor in destabilizing ligands at the L-aspartate pocket.

PMID- 16981732
TI  - Shape-coded silica nanotubes for biosensing.
AB  - Shape-coded silica nanotubes (SNTs) were fabricated on the basis of template
      synthesis as a new dispersible microarray system. The template synthesis of shape
      coded SNTs begins with the fabrication of a porous alumina film that has well
      defined cylindrical pores with two or more different diameter segments by
      multistep anodization of an aluminum substrate. Then, SNTs were fabricated with a
      surface sol-gel method that can control the wall thickness of SNTs on the single
      nanometer level. Attractively, the difference in optical reflectance between the
      segmented parts of individual silica nanotube makes it very convenient to
      identify each nanotube and enables these shape-coded SNTs to work as coding
      materials for biosensing.

PMID- 16981733
TI  - Fabrication of polymeric replicas of cell surfaces with nanoscale resolution.
AB  - We report an approach for fabricating biomimetic surface replicas of cells with
      nanoscale resolution. Fixed cells serve as a template for a two-stage replica
      molding process. Cast from the template, the impression replica contains a
      reproduction of cellular topographical features indented into its surface, and
      cast from the impression replica, the relief replica contains a copy of these
      features protruding from its surface. Various polymers and cells can be utilized,
      and scanning electron microscopy, atomic force microscopy, and white light
      interferometry analyses confirm the replication of nanoscale features. These
      replicas are useful for investigating cellular function and for biomimetic tissue
      engineering.

PMID- 16981734
TI  - Displacement reactions of covalently attached organosilicon monolayers on Si.
AB  - The covalently attached monolayers of alkylsilanes (R(CH(3))(2)SiX) on Si undergo
      complete displacement by the solutions of different organosilanes
      (R'(CH(3))(2)SiX). By varying the reaction time, the degree of displacement can
      be controlled offering a convenient method for the preparation of surfaces with
      mixed functionalities (R and R').

PMID- 16981735
TI  - Creating patterned carbon nanotube catalysts through the microcontact printing of
      block copolymer micellar thin films.
AB  - We report a route for synthesizing patterned carbon nanotube (CNT) catalysts
      through the microcontact printing of iron-loaded poly(styrene-block-acrylic acid)
      (PS-b-PAA) micellar solutions onto silicon wafers coated with thin aluminum oxide
      (Al(2)O(3)) layers. The amphiphilic block copolymer, PS-b-PAA, forms spherical
      micelles in toluene that can form quasi-hexagonal arrays of spherical PAA domains
      within a PS matrix when deposited onto a substrate. In this report, we dip a
      poly(dimethylsiloxane) (PDMS) molded stamp into an iron-loaded micellar solution
      to create a thin film on the PDMS features. The PDMS stamp is then put in contact
      with a substrate, and uniaxial compressive stress is applied to transfer the
      micellar thin film from the PDMS stamp onto the substrate in a defined pattern.
      The polymer is then removed by oxygen plasma etching to leave a patterned iron
      oxide nanocluster array on the substrate. Using these catalysts, we achieve
      patterned vertical growth of multiwalled CNTs, where the CNTs maintain the
      fidelity of the patterned catalyst, forming high-aspect-ratio standing
      structures.

PMID- 16981736
TI  - Evidence of ion transport through surface conduction in alkylsilane
      functionalized nanoporous ceramic membranes.
AB  - Alkylsilane-modified nanoporous ceramic membranes exclude water from their pores
      yet exhibit transmembrane electrical conductivity in aqueous electrolyte
      solutions. That effect was studied using impedance spectroscopy and (29)Si NMR.
      Anodic aluminum oxide membranes with alkylsilane-functionalized pores exhibited a
      transmembrane electrical resistance that increased with the length of the
      hydrocarbon chain. Microstructural studies revealed that the conduction was due
      primarily to a small number of "hydrophilically defective" pores in membranes
      modified by long-chain alkylsilanes and both hydrophilic defects and surface
      conduction in pores modified by short-chain alkylsilanes. Hydroxyl groups in
      short-chain alkylsilane layers act as "water wires" to enable surface ion
      transport. The local concentration of hydroxyl groups decreased with alkylsilane
      chain length, explaining the resistance trend. This constitutes the first direct
      evidence that alkylsilane functionalization affects electrical as well as wetting
      properties.

PMID- 16981737
TI  - Surface-anisotropic polystyrene spheres by electroless deposition.
AB  - Surfaces of sulfate-terminated polystyrene microspheres are anisotropically
      modified with silver nanoparticles covering 20-50% of the sphere surface using
      electroless deposition. A PDMS templating method is employed. Silver
      nanoparticles are found to deposit uniformly onto the exposed sphere surfaces.
      The deposition is diffusion-controlled and the nanoparticles adhere strongly to
      the polystyrene particles despite extensive exposure to ultrasonication. Silver
      content is confirmed by EDAX analysis. The final silver coverage is controlled
      via the PDMS pre-curing conditions.

PMID- 16981738
TI  - Non-affine structural evolution of soft colloidal crystalline latex films under
      stretching as observed via synchrotron X-ray scattering.
AB  - A polymer dispersion consisting of soft latex spheres with a diameter of 135 nm
      was used to produce a crystalline film with face-centered cubic (fcc) packing of
      the spheres. Different from conventional small-molecule and hard-sphere colloidal
      crystals, the crystalline latex film in the present case is soft (i.e., easily
      deformable). The structural evolution of this soft colloidal latex film under
      stretching was investigated by in-situ synchrotron ultra-small-angle X-ray
      scattering. The film exhibits polycrystalline scattering behavior corresponding
      to fcc structure. Stretching results not only in a large deformation of the
      crystallographic structure but also in considerable nonaffine deformation at high
      draw ratios. The unexpected nonaffine deformation was attributed to slippage
      between rows of particles and crystalline grain boundaries. The crystalline
      structure remains intact even at high deformation, suggesting that directional
      anisotropic colloidal crystallites can be easily produced.

PMID- 16981739
TI  - Stable superhydrophobic polybenzoxazine surfaces over a wide pH range.
AB  - In this study, we report on a simple two-step casting process designed to create
      a stable superhydrophobic surface. This method possesses the advantages of being
      both simple and inexpensive as well as utilizing non-fluorine-containing
      compounds. Most interestingly, we found that the as-prepared surface possesses
      superhydrophobic properties not only for pure water but also for corrosive water
      under both acidic and basic conditions. Furthermore, the superhydrophobic
      polybenzoxazine surfaces had excellent environmental stability with regard to
      both heating and organic solvent treatment in terms of the contact angle to
      water.

PMID- 16981740
TI  - Polymerizable cationic gemini surfactant.
AB  - A polymerizable cationic gemini surfactant,
      [CH(2)=C(CH(3))COO(CH(2))(11)N(+)CH(3))(2)CH(2)](2).2Br(-), 1 has been
      synthesized and its basic interfacial properties were investigated (in water and
      in the presence of 0.05 M NaBr). For comparison, the properties of monomeric
      surfactant corresponding to 1, CH(2)=C(CH(3))COO(CH(2))(11)N(+)(CH(3))(3).Br(-),
      2, were also investigated. Parameters studied include cmc (critical micelle
      concentration), C(20) (required to reduce the surface tension of the solvent by
      20 mN/m), gamma(cmc) (the surface tension at the cmc), Gamma(cmc) (the maximum
      surface excess concentration at the air/water interface), A(min) (the minimum
      area per surfactant molecule at the air/water interface), and cmc/C(20) ratio (a
      measure of the tendency to form micelles relative to adsorb at the air/water
      interface). For the polymerizable gemini surfactant, 1, the methacryloxy groups
      at the terminal of each hydrophobic group in a molecule have no contact with the
      air/water interface in the monolayer, whereas for the corresponding monomeric
      surfactant, 2, the methacryloxy group contacts at the interface forming a looped
      configuration like a bolaamphiphile. Polymerized micelles of the gemini
      surfactant are fairly small monodisperse and spherical particles with a mean
      diameter of 3 nm.

PMID- 16981741
TI  - Molecular thermodynamics for micellar branching in solutions of ionic
      surfactants.
AB  - We develop an analytical molecular-thermodynamic model for the aggregation free
      energy of branching portions of wormlike ionic micelles in 1:1 salt solution. The
      junction of three cylindrical aggregates is represented by a combination of
      pieces of the torus and bilayer. A geometry-dependent analytical solution is
      obtained for the linearized Poisson-Boltzmann equation. This analytical solution
      is applicable to saddle-like structures and reduces to the solutions known
      previously for planar, cylindrical, and spherical aggregates. For micellar
      junctions, our new analytical solution is in excellent agreement with numerical
      results over the range of parameters typical of ionic surfactant systems with
      branching micelles. Our model correctly predicts the sequence of stable aggregate
      morphologies, including a narrow bicontinuous zone, in dependence of hydrocarbon
      tail length, head size, and solution salinity. For predicting properties of a
      spatial network of wormlike micelles, our aggregation free energy is used in the
      Zilman-Safran theory. Our predictions are compared with experimental data for
      branching micelles of ionic surfactants.

PMID- 16981742
TI  - Poly(DEAEMa-co-PEGMa): a new pH-responsive comb copolymer stabilizer for
      emulsions and dispersions.
AB  - Stimulus responsive copolymers are an important class of surfactants that are
      attracting growing attention in the literature. When used to stabilize colloids,
      they confer responsiveness to an otherwise nonresponsive system. In this work, a
      new pH-responsive comb copolymer surfactant, poly(DEAEMa-co-PEGMa), where DEAEMa
      and PEGMa are diethylaminoethyl methacrylate and poly(ethylene glycol)
      methacrylate, is introduced and used to stabilize emulsions and particulate
      dispersions. The copolymer contained 70 mol % of DEAEMa. Turbidity versus pH
      measurements and photon correlation spectroscopy of the copolymer solutions
      revealed pH-triggered collapse of the chains above the pK(a). The surface
      activity of the copolymer increased with pH. The minimum surface tension measured
      was 33.6 mN/m at pH = 10. These data enabled identification of the pK(a) for
      poly(DEAEMa-co-PEGMa) as 6.8. The emulsions consisted of tetradecane-in-water and
      had a droplet size in the range 5-11 mum. They were slightly flocculated when the
      pH value was close to the isoelectric point. The emulsions phase separated at low
      pH values. The particulate dispersions were based on carbendazim, which is a
      fungacide, and had an average size of 1.8 mum. The data for the emulsions and
      carbendazim dispersions show that the extent of flocculation decreases with
      decreasing size of the dispersed phase. Analysis of the data suggest that optimum
      emulsion stability occurs in the pH region of 5.3-6.8 as judged by turbidity
      measurements. Electrophoretic mobility measurements as a function of pH for the
      emulsions and carbendazim dispersions reveal a similar isoelectric point in the
      range of 8.5-9.0, which is about two pH units higher than the pK(a) of the
      copolymer. A mechanism that explains the pH-responsive stability of the emulsions
      and dispersions is presented and discussed.

PMID- 16981743
TI  - Investigation of short-time particle dynamics near an interface in the presence
      of nonadsorbed macro-ions.
AB  - The optical technique of total internal reflection microscopy was used to study
      the normal Brownian motion of a single colloidal particle near an interface. The
      measurements were made using a recently developed technique in which the
      diffusion coefficient was determined by the variance of the short-time (Deltat -
      > 0) motion of the particle. Experiments were performed in solutions containing
      either silica nanospheres or clay platelets (Laponite RD) to investigate the
      effect of nonadsorbed material on the dynamics of near-contact particle motion.
      The change in the diffusion coefficient with separation distance between the
      particle and plate in solutions containing nonadsorbed macro-ions was well
      described by the theory developed for simple fluids. These results suggest that,
      in dilute solutions of nonadsorbed material in which the bulk rheological
      properties remain similar to those of the pure fluid, the mobility and diffusion
      coefficient correction factors developed for simple fluids remain valid.

PMID- 16981744
TI  - Optimization of nano-emulsion preparation by low-energy methods in an ionic
      surfactant system.
AB  - The low-energy emulsification method Emulsion Inversion Point (EIP) was used to
      prepare O/W nano-emulsions in the W/potassium oleate-oleic acid
      C(12)E(10)/hexadecane ionic system. This method had not practically been used in
      ionic systems up to now. The resulting droplet sizes, much smaller than those
      obtained with the high-energy emulsification methods, depend on the composition
      (formulation variables) and preparation variables (addition and mixing rate).
      Phase diagrams, rheology measurements, and experimental designs applied to nano
      emulsion droplet sizes obtained were combined to study the formation of these
      nano-emulsions. To obtain small droplet sizes, it is necessary to cross a direct
      cubic liquid crystal phase along the emulsification path, and it is also crucial
      to remain in this phase long enough to incorporate all of the oil into the liquid
      crystal. When nano-emulsion forms, the oil is already intimately mixed with all
      of the components, and it only has to be redistributed. Results show that the
      smaller droplet sizes are obtained when the liquid crystal zone is wide and
      extends to high water content, because in this case, during the emulsification
      process, the system remains long enough in the liquid crystal phase to allow the
      incorporation of all of the oil. Around the optimal formulation variables, the
      liquid crystal zone crossed during emulsification is wide enough to incorporate
      all of the oil whatever mixing or stirring rate is used, and then the resulting
      droplet size is independent of preparation variables. However, when the
      composition is far from this optimum, the liquid crystal zone becomes narrower
      and the mixing of components controls the nano-emulsion formation. High agitation
      rates and/or low addition rates are required to ensure the dissolution of all of
      the oil into this phase.

PMID- 16981745
TI  - Determination of lipid phase transition temperatures in hybrid bilayer membranes.
AB  - The main gel-to-liquid-crystal (LC) phase transition temperature, T(m), of the
      lipid monolayer in hybrid bilayer membranes (HBMs) was investigated using
      vibrational sum frequency spectroscopy (VSFS). In the gel phase, the acyl chains
      of the lipid molecules assume an ordered, all-trans configuration, whereas in the
      LC phase, the acyl chains exhibit a significant number of disordered gauche
      conformers. VSFS has unique sensitivity to the order/disorder transitions in the
      acyl chains and was used to determine T(m) for a series of saturated
      phosphatidylcholine lipids on octadecanethiolate self-assembled monolayers
      (SAMs). The values obtained for T(m) for all lipids studied are significantly
      higher than for the corresponding lipids in vesicles in solution. Additionally,
      the transition widths are broader for the lipids in HBMs. The underlying SAM
      clearly influences the phase behavior of the overlying lipid monolayer.

PMID- 16981746
TI  - Foaming properties of monoglycerol fatty acid esters in nonpolar oil systems.
AB  - Foaming properties of monoglycerol fatty acid esters that have different alkyl
      chain lengths were studied in different nonpolar oils, namely liquid paraffin (LP
      70), squalane, and squalene. The effect of the hydrocarbon chain length of the
      surfactant, the concentration, the nature of the oil, and the temperature on the
      nonaqueous foam stability was mainly studied. Five weight percent of glycerol
      alpha-monododecanoate (monolaurin) formed highly stable foams in squalane at 25
      degrees C, and the foams were stable for more than 14 h. Foam stability of the
      monolaurin/LP 70 and the monolaurin/squalene systems are almost similar, and the
      foams were stable for more than 12 h. Foam stability was decreased as the
      hydrocarbon chain length of the monoglyceride decreased. In the glycerol alpha
      monodecanoate (monocaprin)-oil systems, the foams were stable only for 3-4 h,
      depending on the nature of the oil. However, the foams formed in the glycerol
      alpha-monooctanoate (monocaprylin)-oil systems coarsened very quickly, leading to
      the progressive destruction of foam films, and all of the foams collapsed within
      a few minutes. Foam stability decreased when the oil was changed from squalane to
      squalene, in both monocaprin and monolaurin systems. It was observed that, in the
      dilute regions, these monoglycerides form fine solid dispersions in the
      aforementioned oils at 25 degrees C. At higher temperatures, the solid melts to
      isotropic single-liquid or two-liquid phases and the foams formed collapsed
      within 5 min. Judging from the wide-angle X-ray scattering (WAXS) and the foaming
      test, it is concluded that the stable foams are mainly caused by the dispersion
      of the surfactant solids (beta-crystal) and foam stability is largely influenced
      by the shape and size of the dispersed solid particles.

PMID- 16981747
TI  - A novel and simplified procedure for patterning hydrophobic and hydrophilic SAMs
      for microfluidic devices by using UV photolithography.
AB  - This work describes how selective patterning of hydrophobic and hydrophilic areas
      inside microchannels of microfluidic devices can be achieved by combining well
      known chemical protocols and standard photolithography equipment (365 nm). Two
      techniques have been performed and compared. The first technique is based on the
      preparation of self-assembled monolayers of photocleavable organosilane and the
      second one on photoassisted grafting (365 nm) of self-assembled monolayers (SAMs)
      on a silicon or glass substrate. In the first case, we begin with monolayers
      carrying an o-nitrobenzyl function (hydrophobic area) that is photochemically
      cleaved, revealing a carboxylic acid group (hydrophilic area). The problem is
      that the energy necessary to cleave this monolayer is too high and the reaction
      time is more than 1 h with 50 mW/cm(2) irradiation flux. To overcome this
      practical disadvantage, we propose another approach that is based on the thiol
      ene reaction with benzophenone as photoinitiator. In this approach, a monolayer
      of mercaptopropyltrimethoxysilane (MPTS) is prepared first. Subsequently, a
      hydrocarbon chain is photografted locally onto the thiol layer, forming a
      hydrophobic surface while the reminding unmodified thiol surface is oxidized into
      sulfonic acid (hydrophilic area). We demonstrated the feasibility of this
      approach and synthesized high-quality self-assembled monolayers by UV grafting
      with an irradiation time of 30 s at 365 nm (50 mW/cm(2)). The modified surfaces
      have been characterized by contact angle measurements, X-ray photoelectron
      spectroscopy (XPS), AFM, and multiple internal reflection infrared spectroscopy
      (MIR-FTIR). The difference in the contact angles on the hydrophilic and
      hydrophobic surfaces reached a remarkable 77 degrees. We have also demonstrated
      that this method is compatible with selective surface grafting inside
      microfluidic channels.

PMID- 16981748
TI  - Computer simulation of the adsorption of thiophene in all-silica Y and Na-Y.
AB  - A grand canonical ensemble Monte Carlo simulation is performed to investigate the
      adsorption, heat of adsorption, and distributions of thiophene in all-silica Y
      and Na-Y zeolites. Biased particle insertions and deletions were implemented to
      allow the computation of equilibrium adsorption isotherms of such molecules. The
      calculated number of absorbed thiophene molecules in these zeolites is in good
      agreement with the experimental data. The calculated results show that the number
      absorbed of thiophene molecules in Na-Y is much greater than that in all-silica Y
      over the range of pressure. The calculated heat of adsorption is in good
      agreement with experimental results. The Na-Y zeolite, rather than all-silica Y,
      preferentially adsorbs the thiophene. A distribution analysis of the adsorbed
      phase structure reveals a different adsorption site in the zeolites.

PMID- 16981749
TI  - Reaction of alkenes with hydrogen-terminated and photooxidized silicon surfaces.
      A comparison of thermal and photochemical processes.
AB  - Reagentless micropatterning of hydrogen-terminated Si(111) via UV irradiation
      through a photomask has proven to be a convenient strategy for the preparation of
      ordered bicomponent monolayers. The success of this technique relies upon the
      differential rate of reaction of an alkene with the hydrogen-terminated and
      photooxidized regions of the surface. Monolayer formation can be accomplished
      under either thermal or photochemical conditions. It was observed that, after 3
      h, reaction in neat alkene solution irradiation (Rayonet, 300 nm) afforded the
      expected patterned surface, while thermal conditions (150 degrees C) resulted in
      a partial loss of pattern fidelity. Monolayer properties and formation were
      studied on oxidized and hydrogen-terminated silicon under thermal and
      photochemical initiation, by contact angle, ellipsometry, Fourier transform
      infrared spectroscopy, high-resolution electron energy loss spectroscopy, and X
      ray photoelectron spectroscopy. Results show that alkenes add to silanol groups
      on the silica surface in a manner consistent with acid catalysis: once attached
      to the surface, the silica oxidized the hydrocarbon.

PMID- 16981750
TI  - Factors affecting the preparation and properties of electrodeposited silica thin
      films functionalized with amine or thiol groups.
AB  - Well-adherent sol-gel-derived silica films functionalized with amine or thiol
      groups have been electrogenerated on gold electrodes and both the deposition
      process and the film properties have been studied by various physicochemical
      techniques. Electrodeposition was achieved by combining the formation of a self
      assembled "nanoglue" on the electrode surface, the sol-gel process, and the
      electrochemical manipulation of pH to catalyze polycondensation of the
      precursors. Gold electrodes pretreated with mercaptopropyltrimethoxysilane
      (MPTMS) were immersed in sol solutions containing the selected precursors
      (tetraethoxysilane, TEOS, in mixture with (3-aminopropyl)triethoxysilane, APTES,
      or MPTMS) where they underwent a cathodic electrolysis to generate the hydroxyl
      ions that are necessary to catalyze the formation of the organosilica films on
      the electrode surface. Special attention was given to analyze the effects of
      deposition time and applied potential and to compare APTES and MPTMS films.
      Characterization was made using quartz crystal microbalance, scanning electron
      microscopy, cyclic voltammetry, and atomic force microscopy (including in situ
      monitoring). The electrodeposition process was found to occur at two growing
      rates: a first slow stage giving rise to rather homogeneous, yet rough, films
      with thickness in the sub-mum range (increasing continuously when increasing the
      deposition time), which was followed by a faster gelification step resulting in
      much thicker (>1 microm) and rougher macroporous deposits. These two successive
      situations were observed independently on the applied potential except that more
      cathodic values led to narrower sub-microm ranges (as expected from the larger
      amounts of the electrogenerated hydroxyl catalyst). Thiol-functionalized silica
      films were deposited more rapidly than the amine ones and, for both of them,
      permeability to redox probe was found to decrease when increasing the film
      thickness because of higher resistance to mass transport.

PMID- 16981751
TI  - Distance-dependent metal-enhanced fluorescence from Langmuir-Blodgett monolayers
      of alkyl-NBD derivatives on silver island films.
AB  - We described the effect of fluorophore distance from the silver island films
      (SIFs) on the metal-enhanced fluorescence (MEF) from two newly developed long
      chain nitrobenzoxadiazole derivatives (NBD-C16 and NBD-C18). The well-established
      Langmuir-Blodgett technique is used to deposit the fluorophores at defined
      distances from the SIFs surface, and an inert amphiphilic stearic acid is used to
      control the distance. NBD probes deposited directly on the SIFs surface show the
      highest metal-enhanced fluorescence of approximately 32-fold, and both of the
      probes that were studied show a consistent decrease in metal-enhanced
      fluorescence when increasing the distance from the fluorophore to the SIFs
      surface. The lowest fluorescence enhancement of approximately 4-fold is observed
      for the probes located 90 nm from the SIFs surface. Additionally, we also have
      noticed the shortest fluorescence lifetimes for the NBD probes deposited directly
      onto the SIFs surface, and the lifetimes are consistently increased when
      increasing the distances between the fluorophore and SIFs surfaces. These
      contrasting spectral changes, enhanced fluorescence, and decreased fluorescence
      lifetimes are in accordance with an increase in the rate of radiative decay for
      fluorophores near the silver particles. The present study provides significant
      information on the effect of fluorophore distance on the metal-enhanced
      fluorescence phenomenon.

PMID- 16981752
TI  - D-penicillamine adsorption on gold: an in situ ATR-IR spectroscopic and QCM
      study.
AB  - The adsorption of penicillamine from ethanol on gold was studied in situ by
      attenuated total reflection infrared (ATR-IR) and quartz crystal microbalance
      (QCM) experiments. Both ATR-IR and QCM reveal a fast mass uptake. In ethanol, the
      molecule adopts a zwitterionic form. Upon adsorption, part of the molecules
      deprotonate at the amine group, which is a relatively slow process that goes
      along with a strong shift of the nu(as)(COO(-)) mode. Both ATR-IR and QCM confirm
      a physisorbed layer. ATR-IR furthermore shows that the latter consists of
      zwitterionic molecules only, whereas both zwitterionic and anionic species are
      found in the chemisorbed layer. The infrared spectra of the physisorbed and
      chemisorbed layers are rather different, and the molecules within both layers
      seem to be oriented with respect to the surface. The ATR-IR spectra furthermore
      indicate that all three functional groups of penicillamine (i.e., thiol,
      carboxylate, and amine) interact with the surface, and density functional theory
      calculations support this finding. QCM also shows that the molecule uses
      considerably more space on the surface than molecules of similar size, which
      supports a three-point interaction. The latter leads to a strong anchoring of the
      molecule to the metal, which may explain the exceptional capability of
      penicillamine to bind metals.

PMID- 16981753
TI  - Self-assembly of polystyrene-block-poly(ethylene oxide) copolymers at the air
      water interface: is dewetting the genesis of surface aggregate formation?
AB  - Block copolymer self-assembly at the air-water interface is commonly regarded as
      a two-dimensional counterpart of equilibrium block copolymer self-assembly in
      solution and in the bulk; however, the present analysis of atomic force
      microscopy (AFM) and isotherm data at different spreading concentrations suggests
      a nonequilibrium mechanism for the formation of various polystyrene-b
      poly(ethylene oxide) (PS-b-PEO) aggregates (spaghetti, dots, rings, and chainlike
      aggregates) at the air-water interface starting with an initial dewetting of the
      copolymer spreading solution from the water surface. We show that different
      spreading concentrations provide kinetic snapshots of various stages of self
      assembly at the air-water interface as a result of different degrees of PS chain
      entanglements in the spreading solution. Two block copolymers are investigated:
      MW = 141k (11.4 wt % PEO) and MW = 185k (18.9 wt % PEO). Langmuir compression
      isotherms for the 185k sample deposited from a range of spreading concentrations
      (0.1-2.0 mg/mL) indicate less dense packing of copolymer chains within aggregate
      cores formed at lower spreading concentrations due to a competition between the
      interfacial adsorption of PEO blocks and the kinetic restrictions of PS chain
      entanglements. From AFM analysis of the transferred Langmuir-Blodgett films, it
      is clear that PS chain entanglements in the spreading solution also affect the
      morphological evolution of surface aggregates for both samples, with earlier
      structures being trapped at higher concentrations. At the highest spreading
      concentration for the 141k copolymer, the coexistence of long spaghetti
      aggregates with cellular arrays of holes, along with various transition
      structures, indicates that various surface aggregates evolve from networks of
      rims formed as a result of dewetting of the evaporating spreading solution from
      the water surface.

PMID- 16981754
TI  - Fuzzy ternary particle systems by surface-initiated atom transfer radical
      polymerization from layer-by-layer colloidal core-shell macroinitiator particles.
AB  - We report the synthesis of ternary polymer particle material systems composed of
      (a) a spherical colloidal particle core, coated with (b) a polyelectrolyte
      intermediate shell, and followed by (c) a grafted polymer brush prepared by
      surface-initiated polymerization as the outer shell. The layer-by-layer (LbL)
      deposition process was utilized to create a functional intermediate shell of
      poly(diallyl-dimethylammonium chloride)/poly(acrylic acid) multilayers on the
      colloid template with the final layer containing an atom transfer radical
      polymerization (ATRP) macroinitiator polyelectrolyte. The intermediate core-shell
      architecture was analyzed with FT-IR, electrophoretic mobililty (zeta-potential)
      measurements, atomic force microscopy, and transmission electron microscopy (TEM)
      techniques. The particles were then utilized as macroinitiators for the surface
      initiated ATRP grafting process for poly(methyl methacrylate) polymer brush. The
      polymer grafting was confirmed with thermo gravimetric analysis, FT-IR, and TEM.
      The polymer brush formed the outermost shell for a ternary colloidal particle
      system. By combining the LbL and surface-initiated ATRP methods to produce
      controllable multidomain core-shell architectures, interesting functional
      properties should be obtainable based on independent polyelectrolyte and polymer
      brush behavior.

PMID- 16981755
TI  - Study on the surface density of surface-active substances through total
      reflection X-ray absorption fine structure measurement.
AB  - The total-reflection X-ray absorption fine structure (XAFS) method previously
      employed for the adsorption of dodecyltrimethylammonium bromide (DTAB) at the
      air/water interface was applied to that in the presence of NaBr. The surface
      concentration of the bromide ions Gamma(X)(B) of DTAB and NaBr was evaluated by
      using the Br K-edge absorption jump values of the total-reflection XAFS spectra
      and was compared to the corresponding value Gamma(H)(B) estimated from the
      dependence of surface tension on the bulk concentrations of DTAB m(1) and NaBr
      m(2). The Gamma(X)(B) values trace almost perfectly the Gamma(X)(B) versus m(1)
      curve up to a concentration near the critical micelle concentration (cmc) and
      deviate gradually above the concentration. This behavior is basically similar to
      that of the single DTAB system and ensures that the XAFS method is also
      applicable to the DTAB system, even in the presence of NaBr. In addition, this
      method was extended to the single nonionic amphiphile with covalently bonded
      bromine, and the surface concentrations of 6-bromo-1-hexanol (BrC6OH),
      Gamma(X)(1) and Gamma(H)(B), were evaluated and compared with each other. It was
      found that the Gamma(X)(1) value almost perfectly traces the Gamma(H)(1) versus
      m(1) curve, even at high surface concentrations. The excellent coincidence
      confirmed that the total-reflection XAFS method can be applied to the nonionic
      amphiphile system as well as a cationic surfactant with or without an added salt
      system. Finally, the difference between the Gamma(X)(B) and Gamma(H)(B) values
      observed in the DTAB with and without an added salt system is briefly described.

PMID- 16981756
TI  - Mixed monolayers of alkylated azacrown ethers and palmitic acid at the air-water
      surface.
AB  - The Langmuir films of two alkylated azacrown ethers at the air-water surface were
      characterized using surface pressure-area isotherms, ellipsometry, Brewster angle
      microscopy, and constant-area surface pressure relaxation. The azacrown ether
      molecules aggregate in the monolayer, which significantly stabilizes the film
      against dissolution. Mixed azacrown ether-palmitic acid monolayers were also
      characterized; results suggest that at high compression the two molecules
      interact repulsively. The influence of Cu(II) ions present in the aqueous
      subphase on the single components and mixed monolayer characteristics was also
      studied.

PMID- 16981757
TI  - Ellipsometry of silica nanoparticulate Langmuir-Blodgett films for the
      verification of the validity of effective medium approximations.
AB  - The validity of various effective medium approximations (EMAs) (Bruggeman,
      Maxwell-Garnett) was studied for nanostructured systems, where the scale of
      inhomogeneities is comparable to the wavelength. Langmuir-Blodgett (LB) layers of
      Stober silica nanospheres of diameters between 40 and 129 nm are excellent model
      structures for the experimental verification of the validity of the EMA methods
      in spectroscopic ellipsometry (SE) evaluation. Nanostructured mono- and
      multilayered silica films were investigated by SE and reflectance spectroscopy.
      The effective refractive index and film thickness were determined from the
      results of multiparameter fitting of SE spectra in the 300-759 nm wavelength
      region. The distribution of the effective refractive index in the particulate
      films was calculated assuming an ideal close-packed arrangement of particles. The
      average deviation from such a structure was deduced from the corrected model by
      introducing a "fill factor". In the EMA approximation, the spherical shape of the
      silica particle determines the optical behavior, rather than the "depth
      distribution" of silica or porosity. Therefore, the shape of particles has a
      dominant effect on the optical properties of nanoparticulate LB films.

PMID- 16981758
TI  - Modification of the wettability of a polymeric substrate by pH effect.
      Determination of the surface acid dissociation constant by contact angle
      measurements.
AB  - The wetting properties of a substrate can be changed by chemical reaction. Here,
      we studied simple materials with acid-base properties, by preparing poly(vinyl
      chloride) films containing lauric acid. These substrates constitute simple
      polymeric surfaces the wettability of which can be easily controlled by the acid
      base equilibrium. The roughness of the material was then varied by adding Aerosil
      (hydrophobic fumed silica). We then studied the wettability of these materials
      toward aqueous buffer solutions between pH 2 and 12 from contact angle
      measurements. The variation of the contact angle of a droplet of buffer solution
      with the pH of the solution was described by a simple thermodynamic model
      requiring only two parameters. Thus, we could characterize the acid polymer by an
      effective surface acid dissociation constant the value of which was consistent
      with those obtained with a similar surface. We showed that the behavior of any
      substrate could be described even if the surface geometry was not well-known.

PMID- 16981759
TI  - Relation between contact angle and the cross-sectional area of small, sessile
      liquid drops.
AB  - In this theoretical study, the cross-sectional areas of small, sessile drops were
      calculated for solid surfaces with a wide range of wettability. These areas were
      then used to estimate obstruction of rectangular gas flow channels by sessile
      liquid drops. Our findings suggest that even a small improvement in wettability
      (i.e., a lower contact angle) will lead to a substantial decrease in blockage.
      This work has implications for small channels that contain two-phase flow, such
      as those found in fuel cells.

PMID- 16981760
TI  - Characterizing the pH-responsive behavior of thin films of diblock copolymer
      micelles at the silica/aqueous solution interface.
AB  - The pH-responsive behavior of cationic diblock poly(2-(dimethylamino)ethyl
      methacrylate)-block-poly(2-(diethylamino)ethyl methacrylate) copolymer micelles
      adsorbed at the silica/aqueous solution interface has been characterized. The
      micellar morphology of this copolymer, initially adsorbed at pH 9, can be
      dramatically altered by lowering the solution pH. The original micelle-like
      morphology of the adsorbed copolymer chains at pH 9 completely disappears as the
      pH is decreased to 4, and a brush-like layer structure is produced. This change
      results from protonation of the copolymer chains: the subsequent electrostatic
      repulsions within the film drive the copolymer chains to expand into the aqueous
      phase. Returning the solution pH from 4 to 9 causes this brush-like layer to
      collapse, with atomic force microscopy images suggesting degradation of the film.
      Hence, the pH-responsive behavior of the copolymer film exhibits irreversible
      morphological changes. Measurements of the adsorbed/desorbed amounts of the
      copolymer film were conducted using both a quartz crystal microbalance with
      dissipation monitoring (QCM-D) and optical reflectometry (OR). After an initial
      rinse at both pH values, the OR adsorbed mass becomes almost constant during
      subsequent pH cycling, whereas the corresponding QCM-D adsorbed mass changes
      significantly but reversibly in response to the solution pH. Since the QCM-D
      measures a bound mass that moves in tandem with the surface, the discrepancy with
      the OR data is due to changes in the amount of bound water in the copolymer film
      as a result of the pH-induced changes in surface morphology. The larger effective
      mass observed at pH 4 suggests that the brush-like layer contains much more
      entrapped water than the micellar films at pH 9. The pH dependence of the contact
      angle of the adsorbed film is consistent with the changes observed using the
      other techniques, regardless of whether the solution pH is altered in situ or the
      aqueous solution is completely replaced. In fact, comparison of these two
      approaches provides direct evidence of the exposure of adsorbed micelle core
      blocks to the solution during pH cycling and the concomitant impact upon all the
      other measurements.

PMID- 16981761
TI  - Adsorption thermodynamics of short-chain peptides on charged and uncharged
      nanothin polymer films.
AB  - The present work describes experimental measurements of submolecular-level
      interaction energies involved in the process of peptide adsorption on polymer
      films using surface plasmon resonance spectroscopy. Gibbs energy change on
      adsorption (DeltaG(ad)) for tyrosine, phenylalanine, and glycine homopeptides
      were measured at 25 degrees C and pH 7 on highly uniform, nanothin polymer films,
      and the results were used to predict DeltaG(ad) for homologous homopeptides with
      a larger number of residue units. Nanothin poly(2-vinylpyridine), poly(styrene),
      and poly(1-benzyl-2-vinylpyridinium bromide) films were used for the adsorption
      studies; they were prepared using a graft polymerization methodology. In-situ
      swelling experiments were done with ellipsometry to examine the uniformity of the
      surfaces and to ensure that the graft densities of the different polymer films
      were similar to facilitate the comparison of adsorption results on these
      surfaces. The swelling experiments showed that the films were uniform, and the
      grafting densities were found to be 0.14-0.17 chains/nm(2). For uncharged
      surfaces, predicted and measured DeltaG(ads) values for homopeptides deviated by
      < or =4.9%. To extend this approach to a mixed-residue peptide, measurements were
      made for glycine, phenylalanine, and tyrosine-leucine subunits found in leucine
      enkephalin. The predicted DeltaG(ads) values for leucine enkephalin deviated by
      3.0% and -9.1% for poly(2-vinylpyridine) and poly(styrene) films, respectively.
      Deviations between measured and predicted adsorption energies were larger for the
      charged poly(1-benzyl-2-vinylpyridinium bromide) surface relative to uncharged
      surfaces. While the adsorption energies were found to be additive within
      experimental uncertainties for the charged surface, generally speaking, measured
      uncertainty values were also larger for the charged surface.

PMID- 16981762
TI  - Phlorizin- and 6-ketocholestanol-mediated antagonistic modulation of alamethicin
      activity in phospholipid planar membranes.
AB  - As a result of the interfacial chemical heterogenity, membrane-penetrating
      peptides will experience a dramatic variation in environmental polarity
      manifested via electrical interactions with the surface and dipole potential of
      membranes prone to modulate the membrane insertion and folding of different
      peptides and proteins. Herein we present evidence demonstrating that roughly a 30
      mV, phlorizin-induced lowering of the magnitude of the dipole potential of a
      phosphatidyilcholine membrane leads to a 4-fold increase in the electrical
      activity of embedded alamethicin. The effect is voltage-independent, implying
      that the dipole potential affects the barrier of alamethicin adsorption to the
      membrane rather than the translocation of it across the hydrophobic core. Our
      interpretation points to an enhanced interfacial accumulation of alamethicin
      monomers on the cis side of the membrane caused by a lower value of the cis
      dipole potential, which will promote an elevated activity of alamethicin
      oligomers across the membrane. As expected for a modestly selective ion channel,
      the enhancing effect of such dipole potential changes on the electrical
      conductivity is limited (80 +/- 3 pS before and 100 +/- 2 pS after phlorizin
      addition to the membrane, for the first conductive state of the channel). Our
      study emphasizes the possibility that, by manipulating at will the sign of change
      and the magnitude of the interfacial dipole field, it is possible to modulate the
      extent of the membrane penetration of ion-channel-forming peptides and thereby
      provide deeper insights into mechanisms of protein-lipid and protein-protein
      interactions within membranes.

PMID- 16981763
TI  - Bioactive galactose-branched polyelectrolyte multilayers and microcapsules: self
      assembly, characterization, and biospecific lectin adsorption.
AB  - We describe the fabrication of multilayers and microcapsules with biologically
      designed targeting activity using chemoenzymatic synthesized carbohydrate
      branched polyelectrolytes. A novel cationic d-galactose-branched copolymer
      [poly(vinyl galactose ester-co-methacryloxyethyl trimethylammonium chloride),
      PGEDMC] is alternated with poly(styrene sulfonate) (PSS) to form thin multifilms
      by the layer-by-layer (LbL) technique on such different solid surfaces as quartz
      slides, poly(ethylene terephthalate) (PET) films, silicon wafers, and polystyrene
      (PS) microparticles. The experimental protocols were first optimized on flat,
      smooth silica substrates using UV-vis, contact angle, and atomic force microscopy
      (AFM) measurements. The film properties of PGEDMC/PSS multilayers are modified by
      varying polyelectrolyte concentration, ionic strength, and counteranion types.
      Hollow capsules were formed after the removal of colloidal templates;
      transmission (TEM) and scanning (SEM) electron microscopy were used to verify the
      LbL process integrity. PGEDMC/PSS planar films and capsules carrying beta
      galactose as recognition signals have specific recognition abilities with peanut
      agglutinin (PNA) lectin rather than concanavalin A (Con A) lectin observed by
      fluorescence spectroscopy.

PMID- 16981764
TI  - Exploring gradients of halogens and zinc in the surface and subsurface of Nereis
      jaws.
AB  - The outstanding mechanical properties of impact-bearing tissues, such as Nereis
      jaws, make their morphology and chemical composition a subject of particular
      interest. The complex structure of the jaw was recently reported to exhibit
      molecular gradients that were closely correlated with stiffness and hardness.(18)
      Accordingly, we have explored the spatial distribution and bonding chemistries of
      Zn and the halogens in the surface structure of the jaws. Using secondary ion
      mass spectrometry (SIMS) and scanning electron microscopy (SEM), we found that
      Cl, Br, and I distributions are enhanced in surface layers of the basal protected
      portion of the jaw but are shifted to greater depths toward the exposed jaw tip.
      There are thus two complementary halogen gradients in the jaw: one on the surface
      that decreases from the base to the tip, coupled to an increasing one in the
      subsurface layers. The outer surface coating appeared to have granular
      morphology, in contrast to the anisotropic, fibrous core that dominates the
      subarchitecture. Using X-ray photoelectron spectroscopy (XPS), we discovered that
      Zn, I, and Br in the jaws have single chemical environments whereas chlorine is
      present in two distinct modes (Cl-Zn and Cl-C). Given the inverse relationship
      between surface exposure and halogen abundance in the jaws, it is unlikely that
      the halogens contribute directly to mechanical properties such as wear and
      hardness.

PMID- 16981765
TI  - Transition from nanotubes to micelles with increasing concentration in dilute
      aqueous solution of potassium N-acyl phenylalaninate.
AB  - An aggregation behavior of potassium N-acyl phenylalaninate in dilute aqueous
      solution was investigated. It was found that this surfactant formed large
      aggregates at lower concentrations, which were then transformed to micelles at
      higher concentrations. Fluorescence intensity measurements using a probe were
      used to examine the effects of alkali concentration, acyl chain length, and
      solvent isotope on the aggregation behavior. The influence of the alkali
      concentration suggested that formation of an acid-soap dimer brought about the
      construction of the large particles at very dilute concentrations. Increases in
      both the acyl chain length and replacement of H(2)O with D(2)O resulted in
      stronger hydrophobic interactions; consequently, the large aggregate formation
      was enhanced. This aggregation behavior has not been observed when racemic
      modification of N-acyl phenylalaninate has taken place. By using cryo
      transmission electron microscopy (TEM) with a Zernike differential contrast phase
      plate, it was found that the large aggregates were tubes with bilayer structures,
      which were then transformed into spherical micelles via threadlike micelles with
      increasing concentration due to a drastic increase in the concentration of ionic
      species in the aggregate.

PMID- 16981766
TI  - Supramolecular assembly of cyclodextrin-based nanoparticles on solid surfaces for
      gene delivery.
AB  - In this work, a new approach for surface-mediated gene delivery based on
      inclusion complex formation between the solid surface and delivery vehicles is
      presented. beta-Cyclodextrin (CD) molecules form high-affinity inclusion
      complexes with adamantane. This complexation ability was used to specifically
      immobilize beta-CD-modified poly(ethylenimine) (CD-PEI) nanoparticles on
      adamantane- (AD-) modified self-assembled monolayers. To investigate the
      nanoparticle/surface interaction, CD-PEI-based and PEI-based nanoparticles were
      passed through a surface plasmon resonance flow cell containing the monolayers.
      CD-PEI nanoparticles are specifically immobilized on the chip surface by
      cyclodextrin-adamantane inclusion complex formation. Minimal nanoparticle
      adsorption was detected with PEI-based nanoparticles or on control surfaces.
      Competition studies with free cyclodextrins reveal that the multivalent
      interactions between CD-PEI nanoparticles and the adamantane-modified surface
      results in significantly higher binding affinity than single cyclodextrin
      adamantane complexes. Immobilized nanoparticles were characterized by atomic
      force microscopy and quantified by fluorescence assay. Thus, the ability of CD
      PEI nanoparticles to form inclusion complexes can be exploited to attain
      specific, high-affinity loading of delivery vehicles onto solid surfaces.

PMID- 16981767
TI  - Bimodal polymer mushrooms: compressive forces and specificity toward receptor
      surfaces.
AB  - End-grafted poly(ethylene glycol) (or PEG) polymer chains are used to extend the
      in vivo circulation time of targeted liposomes and nanoparticles; however, the
      most efficacious structure for also imparting high target specificity remains
      unknown. Using the surface force apparatus, we have measured the specific and
      nonspecific forces between bimodal mixtures of grafted polymer mushrooms and
      model receptor surfaces. Specifically, supported lipid membranes anchoring 2000
      or 5000 Da PEG with a controlled fraction of PEG(2000) bearing biotin ligands
      were compressed against opposing streptavidin surfaces. The presence of the
      longer 5000 Da chain increased the steric repulsion of the bimodal mushroom layer
      and thus decreased the net adhesive force when shorter chains were ligated.
      However, the 5000 Da chain did not detectably alter the distance where ligand
      receptor binding occurs and adhesion begins. This latter result is in good
      agreement with theoretical predictions based on summing the repulsive steric and
      attractive bridging forces. Further, all ligated structures adhered to receptors
      under both static and dynamic fluid flow conditions. The dynamic movement of the
      flexible PEG tethers permitted ligand-receptor bonds to form far beyond the
      equilibrium edge of the bimodal mushroom layer. This work demonstrates that
      liposome targeting should be enhanced by grafting ligands to liposomes with a
      tether that has a contour length longer than the equilibrium height of the
      bimodal mushroom layer.

PMID- 16981768
TI  - ATR-FTIR spectroscopy reveals bond formation during bacterial adhesion to iron
      oxide.
AB  - The contribution of various bacterial surface functional groups to adhesion at
      hematite and ZnSe surfaces was examined using attenuated total reflectance (ATR)
      Fourier transform infrared (FTIR) spectroscopy. When live Shewanella oneidensis,
      Pseudomonas aeruginosa, and Bacillus subtilis cells were introduced to a
      horizontal hematite (alpha-Fe(2)O(3))-coated internal reflection element (IRE),
      FTIR peaks emerged corresponding to bacterial phosphate group binding. These IR
      peaks were not observed when bacteria were introduced to the uncoated ZnSe IRE.
      When cells were added to colloidal suspensions of alpha-Fe(2)O(3) at pH 7,
      spectra included peaks corresponding to P-OFe and nu(COOH), the latter being
      attributed to bridging of carboxylate at mineral surface OH groups. Selected
      model organic compounds with P-containing functionalities (phenylphosphonic acid
      [PPA], adenosine 5'-monophosphate [AMP], 2'-deoxyadenyl(3'-->5')-2'
      deoxyadenosine [DADA], and deoxyribonucleic acid [DNA]) produce spectra with
      similar peaks corresponding to P-OFe when adsorbed to alpha-Fe(2)O(3). The data
      indicate that both terminal phosphate/phosphonate and phosphodiester groups,
      either exuded from the cell or present as surface biomolecules, are involved in
      bacterial adhesion to Fe-oxides through formation of innersphere Fe
      phosphate/phosphonate complexes.

PMID- 16981769
TI  - Fabrication of phytic acid sensor based on mixed phytase-lipid Langmuir-Blodgett
      films.
AB  - This paper reports the surface activity of phytase at the air-water interface,
      its interaction with lipid monolayers, and the construction of a new phytic acid
      biosensor on the basis of the Langmuir-Blodgett (LB) technique. Phytase was
      inserted in the subphase solution of dipalmitoylphosphatidylglycerol (DPPG)
      Langmuir monolayers, and its incorporation to the air-water interface was
      monitored with surface pressure measurements. Phytase was able to incorporate
      into DPPG monolayers even at high surface pressures, ca. 30 mN/m, under
      controlled ionic strength, pH, and temperature. Mixed Langmuir monolayers of
      phytase and DPPG were characterized by surface pressure-area and surface
      potential-area isotherms, and the presence of the enzyme provided an expansion in
      the monolayers (when compared to the pure lipid at the interface). The enzyme
      incorporation also led to significant changes in the equilibrium surface
      compressibility (in-plane elasticity), especially in liquid-expanded and liquid
      condensed regions. The dynamic surface elasticity for phytase-containing
      interfaces was investigated using harmonic oscillation and axisymmetric drop
      shape analysis. The insertion of the enzyme at DPPG monolayers caused an increase
      in the dynamic surface elasticity at 30 mN m(-)(1), indicating a strong
      interaction between the enzyme and lipid molecules at a high-surface packing.
      Langmuir-Blodgett (LB) films containing 35 layers of mixed phytase-DPPG were
      characterized by ultraviolet-visible and fluorescence spectroscopy and crystal
      quartz microbalance nanogravimetry. The ability in detecting phytic acid was
      studied with voltammetric measurements.

PMID- 16981770
TI  - Gelatin hydrogels cross-linked with bis(vinylsulfonyl)methane (BVSM): 1. The
      chemical networks.
AB  - This paper deals with chemical gelation of gelatin in the presence of a cross
      linker, bis(vinylsulfonyl)methane (BVSM), which is able to create covalent C-N
      bonds with amine groups. The investigation is performed at 40 degrees C, where no
      triple helices are present. Gelatin is in random coil conformation. The influence
      of various parameters (gelatin concentration, cross-linker concentration, and pH
      (number of reacting sites along the gelatin chain)) was examined. Gel formation
      was followed by rheological and thermodynamic measurements (microcalorimetry)
      versus time (kinetic measurements). Furthermore, the storage moduli were compared
      to the number of links formed in the course of gelation. The experiments show
      that, within the experimental range investigated, a fully homogeneous network is
      not reached; the chemical gels, even upon completion of the reactions, are still
      in the critical domain, near the threshold. A power law behavior was put in
      evidence for the shear modulus versus the distance to the gel point, expressed as
      the concentration of links per gelatin chain. The exponent (f = 3.4 +/- 0.3) is
      close to that expected for the vulcanization of long chains. The storage moduli
      can be superposed on a single curve where the abscissa is the product of the
      number of C-N links per unit volume and the gelatin concentration at an exponent
      equal to -0.76 +/- 0.03. This exponent suggests the role of entanglements for
      interchain cross-linking.

PMID- 16981771
TI  - Gelatin hydrogels cross-linked with bisvinyl sulfonemethyl. 2. The physical and
      chemical networks.
AB  - This paper deals with the physical and the chemical gelation of gelatin in the
      presence of a reactant, bisvinyl sulfonemethyl (BVSM). The strategy of this
      investigation is to separate the contributions of the two types of cross-links in
      order to deduce the resultant elasticity of the network. In addition, the
      question raised by several authors concerning an increase of the thermal
      stability of the triple helices in the presence of cross-links was examined by
      using several techniques. In this study, the concentration of gelatin and BVSM
      were kept constant, while the influence of the thermal protocols was put in
      evidence. The gel formation was followed by rheological, thermodynamic
      (microcalorimetry), and optical spectroscopy (optical rotation) measurements. The
      results demonstrate the large differences which arise on the storage moduli by
      changing the thermal protocols. Cross-linking of the networks in the presence of
      the triple helices induce a heterogeneous repartition of the bonds, which can
      form along the triple helices and at the end of the sequences. Consequently, the
      rubber like network obtained by denaturation of the triple helices is still
      reminiscent of the initial twist of the chains, and a large modulus is observed,
      as if rigid segments were still present (storage modulus 10 times larger than for
      random cross-linking). The hydrogels have an elastic modulus which is larger that
      the addition of the physical and chemical contributions. The interpretation of
      the network elasticity is based on the predominant role of the rigid rods of
      triple helices, where the BVSM cross-links can either modify the ratio between
      the apparent length and distance between rods, l/d, and/or increase the rigidity
      of the interchain connections, which are loose coils for the physical gels. The
      hydrogels investigated have a network which is still close to the percolation
      threshold of the physical gel, and therefore, the statistical models known for
      well developed networks cannot be directly validated in these experimental
      conditions.

PMID- 16981772
TI  - Dendrimer-tuned formation of fluorescent organic microcrystals. Influence of dye
      hydrophobicity and dendrimer charge.
AB  - The reprecipitation method is a simple and useful way to prepare microcrystals
      through a solvent exchange process. It was applied to three fluorescent dyes of
      the 4-amino-7-nitrobenz-2-oxa-1,3-diazole series. Compounds 1, 2, and 3 differ by
      the length of the alkyl chain, which comprises 8, 12, and 18 carbon atoms,
      respectively. The reprecipitation process was first studied in water, in the
      absence of additives. The kinetics was monitored by UV/vis absorption
      spectroscopy. The size and shape of the microparticles were analyzed by
      fluorescence microscopy and transmission electron microscopy. Dyes 1 and 2 lead
      to microcrystals, the whole process taking much more time for 2 than for 1. The
      long-chained dye 3 only gave stable aggregates. Therefore, it appears that the
      hydrophobicity of the organic dye markedly influenced the reprecipitation
      process. The latter was then studied in the presence of additives.
      Poly(amidoamine) dendrimers, terminated by 64 carboxylate or amino groups were
      placed in the reprecipitation medium. They had little effect upon the formation
      of aggregates for dye 3. In contrast, they drastically accelerated the
      reprecipitation of 1 and 2 and tuned the size and shape of the microcrystals.
      Platelets and spindles were thus obtained by varying the nature of the dendrimer,
      and their optical properties were briefly investigated.

PMID- 16981773
TI  - Formation mechanisms and properties of semifluorinated molecular gradients on
      silica surfaces.
AB  - The goal of this study is to elucidate the formation of molecular gradients made
      of semifluorinated organosilanes (SFOs) on flat substrates by using a methodology
      developed by Chaudhury and Whitesides (Science 1992, 256, 1539). We use surface
      sensitive combinatorial near-edge X-ray absorption fine structure (combi-NEXAFS)
      spectroscopy to measure the position-dependent concentration and orientation of
      SFO molecules in SFO molecular gradients on flat silica surfaces. Using the combi
      NEXAFS data, we establish the correlation between the fraction of the
      F(CF(2))(8)(CH(2))(2)- species on the substrate and the average tilt angle of the
      -(CF(2))(8)F group in the SFO as a function of the deposition gas medium (air vs
      nitrogen) and the end group around the silicon atom (monofunctional vs
      trifunctional). In addition, we utilize the gradient geometry to comprehend the
      mechanism of formation of SFO self-assembled monolayers (SAMs). Specifically, we
      provide evidence that depending on the nature of the end group in the SFO and the
      vapor phase the SFO molecules add themselves into the existing SAMs either as
      individual molecules or as multimolecular complexes.

PMID- 16981774
TI  - Silica structures templated on fibers of tetraalkylphosphonium salt gelators in
      organogels.
AB  - Phosphonium cations (18(n)RP(+)) consisting of three or four n-octadecyl chains
      and R = PhCH(2) or C(m)H(2)(m+1) (m = 1-5 or 12) when n = 3 and with iodide,
      bromide, chloride, fluoride, or perchlorate anions are used to gelate and
      polymerize solutions of 2-10 wt % tetraethyl orthosilicate in ethanol, benzene,
      tetrahydrofuran, and dimethyl sulfoxide using acid or base catalysis and under
      hydrolytic or nonhydrolytic conditions. These are the simplest low-molecular-mass
      organic gelator structures of which we are aware that have been able to template
      silica. The silica objects that are obtained after the hydrolytic sol-gel process
      include porous, spherulitic, and tubular objects in the size range of several
      micrometers to tens of nanometers. Their specific shapes and sizes depend on the
      specific conditions of the hydrolytic sol-gel process, including the nature of
      the catalyst. The electrostatic interaction between silicate intermediates and
      gelator strands is the driving force for templating. The template effect is
      strongly influenced by several factors, including (1) the competition between
      silicate/solvent and silicate/template interactions, (2) the period of the sol
      gel process, (3) the hardness of the anion of the gelator salt, (4) the surface
      tension of the solvent, (5) and the sequence of drying and template removal
      processes. The nature of the R group influences the stability of the molecular
      gels but appears to have little effect on the silica morph obtained. In addition,
      it is shown in one case, where a direct comparison is possible, that the fibers
      of one of our phosphonium salts are a much more efficient template for silica
      than those of the corresponding ammonium salt (with its "harder" cationic
      center). The specific nature of the objects and the conditions under which they
      can be formed are discussed.

PMID- 16981775
TI  - Anion effect on the nanostructure of a metal ion binding self-assembling peptide.
AB  - Effects of copper salts containing different anions (SO(4)(2)(-), Cl(-), and
      NO(3)(-)) on the self-assembly of a designed peptide EAK16(II)GGH with affinity
      for Cu(2+) have been investigated. The peptide secondary structure, self
      assembled nanostructures, and surface activity were observed to depend strongly
      on the type of anion. Over a salt concentration range from 0.05 to 10.0 mM,
      SO(4)(2)(-) induced long fiber formation, whereas Cl(-) and NO(3)(-) caused short
      fiber formation. The fiber length increased with copper sulfate concentration,
      but the concentration of copper chloride and copper nitrate did not affect the
      peptide nanostructures significantly. Analysis by Fourier transform infrared
      spectroscopy (FTIR) revealed that the addition of the copper salts tended to
      cause the peptide conformation to change from alpha-helix/random coil to beta
      sheet, the extent to which depended on the anion type. This evidence of the anion
      effect was also supported by surface tension measurements using the axisymmetric
      drop shape analysis-profile (ADSA-P) technique. An explanation for the effect of
      anions on the peptide self-assembly was proposed. The divalent anion SO(4)(2)(-)
      might serve as a bridge by electrostatically interacting with two lysine residues
      from different peptide molecules, promoting beta-sheet formation. The extensive
      beta-sheet formation may further promote peptide self-assembly into long fibers.
      On the other hand, monovalent anions Cl(-) and NO(3)(-) may only
      electrostatically interact with one charged residue of the peptide; hence, a
      mixed secondary structure of alpha-helix/random coil and beta-sheet was observed.
      This observation might explain the predominant formation of short fibers in
      copper chloride and copper nitrate solutions.

PMID- 16981776
TI  - Poly(vinyl pyrrolidone): a dual functional reductant and stabilizer for the
      facile synthesis of noble metal nanoplates in aqueous solutions.
AB  - Poly(vinyl pyrrolidone) (PVP) has been extensively used in the solution-phase
      synthesis of many types of colloidal particles, where it is mainly considered as
      a steric stabilizer or capping agent with a major role to protect the product
      from agglomeration. In a recent study, we discovered that the hydroxyl end groups
      of PVP could also serve as a very mild reductant for kinetically controlled
      synthesis of Ag nanoplates with yields as high as 75%. Here we further
      demonstrate that hydroxyl-terminated PVP is also a well-suited reductant for the
      aqueous synthesis of circular, triangular, and hexagonal nanoplates made of other
      noble metals including Pd, Au, and Pt. The reduction kinetics of a metal salt by
      the hydroxyl end groups of PVP can be maneuvered in at least two different ways
      to facilitate the evolution of plate morphology: (i) by adjusting the molar ratio
      of PVP to the salt precursor and (ii) by altering the molecular weight of PVP.
      Unlike previously reported studies of Ag and Au thin plates, light was found to
      have a negligible role in the present synthesis.

PMID- 16981777
TI  - Fabrication of chemically microstructured polymer brushes.
AB  - In this paper, a new and simple pathway to fabricate polymer brush layers with
      lateral control over the chemical composition is described. The process combines
      two subsequent free radical grafting from steps: in the first step, a
      micropatterned polymer brush is grown by photochemical initiation of the polymer
      growth from the surface through a mask in direct contact. The uncoated areas are
      then backfilled with a second polymer brush by using the unreacted surface-bound
      initiator molecules to thermally trigger a second polymerization. As an example
      for the overall process, the co-assembly of a micropatterned, soft, water
      swellable layer consisting of the two-brush system poly(methacrylic acid) (PMAA)
      poly(hydroxyethyl methacrylate) (PHEMA) is demonstrated.

PMID- 16981779
TI  - Size-controlled synthesis of monodispersed silver nanoparticles capped by long
      chain alkyl carboxylates from silver carboxylate and tertiary amine.
AB  - Monodispersed silver nanoparticles capped by long-chain alkyl carboxylates were
      prepared by the reaction of silver carboxylate with tertiary amine at 80 degrees
      C for 2 h. This approach is a unique, size-controlled synthetic method for the
      large-scale preparation of silver nanoparticles. Long-chain alkyl carboxylate
      derived from a precursor acts as a stabilizer to avoid the aggregation of silver
      nanoparticles and to control particle size. In addition, amine plays an important
      role both as a reagent to form a thermally unstable, amine-coordinated
      intermediate, bis(amine)silver(I) carboxylate, and as a mild reducing agent for
      the intermediate to produce nanoparticles at a low temperature. The silver core
      and carboxylate-capping ligand of silver nanoparticles were characterized by
      various techniques such as transmission electron microscopy, optical absorption
      spectroscopy, powder X-ray diffraction, X-ray photoelectron spectroscopy, gas
      chromatograph mass spectroscopy, and thermogravimetric and differential thermal
      analysis. The diameter of the nanoparticles can be strongly influenced by the
      alkyl chain length and the structure of the carboxylate. The average diameters of
      the silver nanoparticles were controlled to less than 5 nm in the case of silver
      carboxylate with a single alkyl chain length of 13 or 17 carbon atoms. On the
      contrary, the average diameters of silver nanoparticles became large and
      polydisperse in the case of silver carboxylate with a chain length of 7 carbon
      atoms or a branched chain. In comparing triethylamine with trioctylamine, there
      was no obvious effect to regulate the size distribution of the nanoparticles
      because they could not function as a capping ligand of the nanoparticles due to
      their weak coordination to silver. In addition, the heat treatment of silver
      nanoparticles in solution rather than in the solid state was effective for the
      growth of particles while maintaining narrow size distributions.

PMID- 16981778
TI  - Superhydrophobic behavior of a perfluoropolyether lotus-leaf-like topography.
AB  - We demonstrate the fabrication of 2-D arrays of nanopillars made from
      perfluoropolyether derivatives using a porous anodic aluminum oxide membrane as a
      template. Pretexturing the aluminum prior to anodization enables one to engineer
      multiple morphological length scales and thereby synthesize a lotus-leaf-like
      topography. Both nanopillars on a flat surface and on a lotus-leaf-like topology
      exhibit superhydrophobicity, low contact angle hysteresis, and self-cleaning.

PMID- 16981780
TI  - Large damage threshold and small electron escape depth in X-ray absorption
      spectroscopy of a conjugated polymer thin film.
AB  - The information depth of near-edge X-ray absorption fine structure spectroscopy
      in the total electron yield mode (TEY-NEXAFS) is given by the escape depth of the
      TEY electrons z(TEY). This is determined by the effective ranges both of the
      inelastically scattered secondary electrons and of the primary excited electron
      before they thermalize below the vacuum level. For regioregular poly(3
      hexylthiophene) (rreg-P3HT) thin films, we have measured the total electron
      emission efficiency to be 0.028 +/- 0.005 e/ph at an incident photon energy of
      320 eV. The range of the primary electron was computed using optical dielectric
      loss theory to be 7.5 nm. The range of the secondary electrons was then found by
      modeling to be 3.0 nm. This gives z(TEY) to be 2.5 nm, which is considerably less
      than the often-assumed value of 10 nm in the literature. It is also considerably
      smaller than the computed electron-electron scattering inelastic mean free path
      in the material, which suggests the predominance of electron-phonon scattering.
      Thus, TEY-NEXAFS has sufficient surface sensitivity to probe the frontier
      molecular layers of these organic conjugated polymers. In a second aspect of this
      report, the rreg-P3HT films have been characterized by in-situ core and valence
      photoemission spectroscopies and by ex-situ microattenuated total-reflection
      vibrational spectroscopy as a function of irradiation dose. No damage was
      observed in composition, bonding, orientation, and surface morphology under
      typical TEY-NEXAFS spectral acquisition conditions. For an integrated TEY that
      exceeds 2 x 10(-3) C cm(-2), however, the material degrades via alkyl side-chain
      dehydrogenation to unsaturated units, cross linking, ring opening of the
      backbone, and sulfur extrusion. Given that secondary electrons are the dominant
      cause of radiation damage, this exposure threshold measured by integrated TEY
      should also be valid at other X-ray energies.

PMID- 16981781
TI  - Replica molding of high-aspect-ratio polymeric nanopillar arrays with high
      fidelity.
AB  - Polymeric nanostructures with high aspect ratios, so-called nanopillars, are of
      interest for a wide range of applications. However, it remains a challenge to
      fabricate high-density, polymeric nanopillars using soft lithography when the
      feature size is decreased to hundreds of nanometers and the structures are close
      to each other. Here, we investigate the fidelity of replica molding technique to
      fabricate polymer nanopillar arrays with diameters ranging from 300 nm to 1 mum,
      and we compare the experimental results to the theoretical prediction to
      understand the nature of the instability of nanopillars. Nanopillars molded from
      soft materials, poly(dimethylsiloxane) (PDMS), mainly ground collapse due to the
      adhesive force when the aspect ratio is above 6, whereas those from stiffer
      materials, polyurethane and epoxy, collapse laterally at a much higher aspect
      ratio (>/=12), of which the critical value is dependent on the nanopillar's
      feature size, spacing, height, and shape. Further, we attempt to restore the
      collapsed high-aspect-ratio nanopillars using supercritical CO(2) drying.

PMID- 16981782
TI  - Photophysical behavior of terpyridine-lanthanide ion complexes incorporated in a
      poly(N,N-dimethylacrylamide) hydrogel.
AB  - Poly(N,N-dimethylacrylamide) hydrogel forms complexes with terpyridine and
      various trivalent ions, like Eu(3+), Tb(3+), Gd(3+), and In(3+). The hydrogel can
      be obtained in three different phases: swollen with water, lyophilized (i.e.,
      dried by freeze-drying), where it loses the solvent but preserves the swollen
      configuration, and dried in the air where it shrinks. The three hydrogel phases
      affect the type of complex formed between terpyridine and the metal ion. Thus, in
      the swollen and lyophilized phases, metal-centered emission can be obtained by
      energy transfer from the excited ligand. In the shrunk phase, an intense green
      fluorescence is emitted, which is ligand-centered and is independent of the
      complexed ion. In the absence of any ion, the ligand emits blue luminescence,
      independently of the hydrogel phase. In the presence of europium(III) ions, blue,
      green, or red emission can be thus produced at appropriate compositions and
      hydrogel phases. Analysis of the photophysical behavior of the polymer-ligand
      metal ion complex is related with the photophysical behavior of the ligand and
      its complexes in various pure solvents.

PMID- 16981783
TI  - Design of antibacterial surfaces by a combination of electrochemistry and
      controlled radical polymerization.
AB  - In this paper we report a new method for the electrochemical deposition of a
      metal/polymer composite layer on a conducting substrate. The electrochemical
      solution is a mixture of an acrylate (ethyl acrylate, EA; 2-phenyl-2-(2,2,6,6
      tetramethylpiperidin-1-yloxy)ethyl acrylate, PTEA; 8-quinolinyl acrylate, 8QA), a
      metallic salt (silver(I) acetate), and a conducting salt in dimethylformamide.
      The process has been first studied with EA as the polymer precursor and then
      extended to PTEA and 8QA, respectively, with the purpose to prepare antibacterial
      surfaces. The final coating has been characterized by attenuated total reflection
      Fourier transform infrared spectroscopy, energy-dispersive X-ray analysis,
      environmental scanning electron microscopy, and atomic force microscopy. All the
      silver-containing coatings were effective against Gram-negative bacteria
      Escherichia coli. Bacteria Staphylococcus aureus could not adhere to the
      Ag(0)/polyacrylate films deposited on stainless steel.

PMID- 16981787
TI  - Intensity modulated radiation therapy: a review of current practice and future
      directions.
AB  - The use of intensity modulated radiation therapy (IMRT) has been rapidly growing
      in the United States. This technology is now being used in a multitude of
      academic and community centers throughout the country and is being incorporated
      into the treatment of cancers in almost every anatomical site, most commonly head
      and neck cancer, central nervous system tumors, and prostate cancer. In addition,
      current protocols are investigating the use of IMRT for the treatment of breast
      cancer, lung cancer, abdominal/retroperitoneal malignancies, and gynecological
      diseases. This article presents a brief technical review of IMRT and addresses
      specific clinical concerns and caveats that radiation oncologists should be aware
      of when utilizing this technology.

PMID- 16981788
TI  - New developments in intensity modulated radiation therapy.
AB  - As intensity modulated radiation therapy (IMRT) becomes routine clinical
      practice, its advantages and limitations are better understood. With these new
      understandings, some new developments have emerged in an effort to alleviate the
      limitations of the current IMRT practice. This article describes a few of these
      efforts made at the University of Maryland, including: i) improving IMRT
      efficiency with direct aperture optimization; ii) broadening the scope of
      optimization to include the mode of delivery and beam angles; and iii) new
      planning methods for intensity modulated arc therapy (IMAT).

PMID- 16981789
TI  - Clinical implementation of adaptive helical tomotherapy: a unique approach to
      image-guided intensity modulated radiotherapy.
AB  - Image-guided IMRT is a revolutionary concept whose clinical implementation is
      rapidly evolving. Methods of executing beam intensity modulation have included
      individually designed compensators, static multi-leaf collimators (MLC), dynamic
      MLC, and sequential (serial) tomotherapy. We have developed helical tomotherapy
      as an innovative solution to overcome some of the limitations of other IMRT
      systems. The unique physical design of helical tomotherapy allows the realization
      of the concepts of adaptive radiotherapy and conformal avoidance. In principle,
      these advances should improve normal tissue sparing and permit dose
      reconstruction and verification, thereby allowing significant biologically
      effective dose escalation. Recent radiobiological findings can be translated into
      altered fractionation schemes that aim to improve the local control and long-term
      survival. This strategy is being tested at the University of Wisconsin using
      helical tomotherapy with its highly precise delivery and verification system
      along with meticulous and practical forms of immobilization. Innovative
      techniques such optical guidance, respiratory gating, and ultrasound assessments
      are being designed and tailored for helical tomotherapy use. The intrinsic
      capability of helical tomotherapy for megavoltage CT (MVCT) imaging for IMRT
      image-guidance is being optimized. The unique features of helical tomotherapy
      might allow implementation of image-guided IMRT that was previously impossible or
      impractical. Here we review the technological, physical, and radiobiological
      rationale for the ongoing and upcoming clinical trials that will use image-guided
      IMRT in the form of helical tomotherapy; and we describe our plans for testing
      our hypotheses in a rigorous prospective fashion.

PMID- 16981790
TI  - Independent evaluations of IMRT through the use of an anthropomorphic phantom.
AB  - Intensity-modulated radiation therapy (IMRT) has gained rapid and wide-spread
      acceptance in the radiation oncology community for its ability to create dose
      distributions that conform to the convoluted shapes of many tumors. It is a
      complicated treatment technique, for which quality assurance procedures are
      correspondingly complicated and labor intensive. Several of the cooperative
      cancer study groups that conduct clinical trials under the auspices of the
      National Cancer Institute have required participating institutions to seek
      credentialing before enrolling patients in trials involving IMRT. The
      Radiological Physics Center has conducted such credentialing programs through the
      use of anthropomorphic phantoms that evaluate the planning and delivery of IMRT.
      The experience obtained through the irradiation of the phantoms by a number of
      institutions demonstrates that institutions vary significantly in their ability
      to deliver doses and dose distributions that agree with their own treatment
      plans.

PMID- 16981791
TI  - Dynamic IMRT treatments of sinus region tumors: comparison of Monte Carlo
      calculations with treatment planning system calculations and ion chamber
      measurements.
AB  - Results are presented comparing Monte Carlo (MC) calculations for dynamic IMRT
      treatments of tumors in the sinus region with Eclipse treatment planning system
      dose calculations, and ion chamber measurements. The EGS4nrc MC code, BEAMnrc,
      was commissioned to simulate a Varian 21Ex Linac for both open and IMRT fields.
      The accuracy of the simulation for IMRT plans was evaluated using a head phantom
      by comparing MC, Eclipse, TLD results, and ion chamber in solid water phantom
      measurements. The MC code was then used to simulate dose distributions for five
      patients who were treated using dynamic IMRT for tumors in the sinus region. The
      results were compared with absolute and relative dose distributions calculated
      using Eclipse (pencil beam, modified-Batho inhomogeneity correction). Absolute
      dose differences were also compared with ion chamber results. Comparison of the
      doses calculated on the head phantom using MC, compared with Eclipse, ion
      chamber, and TLD measurements showed differences of -3.9%, -1.4%, and -2.0%,
      respectively (MC is colder). Relative dose distributions for the patient plans
      calculated using MC agreed well with those calculated using Eclipse with respect
      to targets and critical organs, indicating the modified-Batho correction is
      adequate. Average agreement for mean absolute target doses between MC and Eclipse
      was -3.0 +/-; 2.3% (1 s.d.). Agreement between ion chamber and Eclipse for these
      patients was -2.2 +/- 1.9%, compared with 0.2 +/- 2.0% for all head and neck IMRT
      patients. When Eclipse doses were corrected based on ion chamber results,
      agreement between MC and Eclipse was -0.7 +/- 2.0%, indicating a small systematic
      uncertainty in the doses calculated using the treatment planning system for this
      subset of patients.

PMID- 16981792
TI  - Retinoblastoma with cerebrospinal fluid metastasis treated with orbital and
      craniospinal irradiation using IMRT.
AB  - A 4-year-old male child presented with history of leucocoria, photophobia, and
      progressive visual deterioration in the left eye. Clinical examination and
      computed tomography revealed a unilateral retinoblastoma involving the left
      globe. He underwent enucleation of the left eye and was referred for adjuvant
      radiotherapy in view of optic nerve infiltration up to the line of resection.
      However, he did not report for treatment and presented six months later with a
      recurrent mass in the left orbit with intracranial extension. Cerebrospinal fluid
      (CSF) cytology was positive for malignant retinoblastoma cells. He received
      multiagent chemotherapy with vincristine, carboplatin, and etoposide along with
      intrathecal methotrexate. Although the recurrent orbital mass reduced
      significantly with chemotherapy, malignant cells persisted in the CSF. He was
      subsequently treated using intensity modulated radiation therapy (IMRT) to treat
      the left orbital mass along with craniospinal axis irradiation. Computed
      tomography done at three and nine months after completion of radiotherapy showed
      complete disappearance of orbital tumor. CSF cytology also showed no evidence of
      malignant cells.

PMID- 16981793
TI  - Single course IMRT plan to deliver 45 Gy to seminal vesicles and 81 Gy to
      prostate in 45 fractions.
AB  - We treat prostate and seminal vesicles (SV) to 45 Gy in 25 fractions (course 1)
      and boost prostate to 81 Gy in 20 more fractions (course 2) with Intensity
      Modulated Radiation Therapy (IMRT). This two-course IMRT with 45 fractions
      delivered a non-uniform dose to SV and required two plans and two QA procedures.
      We used Linear Quadratic (LQ) model to develop a single course IMRT plan to treat
      SV to a uniform dose, which has the same biological effective dose (BED) as that
      of 45 Gy in 25 fractions and prostate to 81 Gy, in 45 fractions. Single course
      IMRT plans were compared with two-course IMRT plans, retrospectively for 14
      patients. With two-course IMRT, prescription to prostate and SV was 45 Gy in 25
      fractions and to prostate only was 36 Gy in 20 fractions, at 1.8 Gy/fraction.
      With 45-fraction single course IMRT plan, prescription to prostate was 81 Gy and
      to SV was 52 or 56 Gy for a alpha/beta of 1 and 3, respectively. 52 Gy delivered
      in 45 fractions has the same BED of 72 Gy3 as that of delivering 45 Gy in 25
      fractions, and is called Matched Effective Dose (MED). LQ model was used to
      calculate the BED and MED to SV for alpha/beta values of 1-10. Comparison between
      two-course and single course IMRT plans was in terms of MUs, dose-max, and dose
      volume constraints (DVC). DVC were: 95% PTV to be covered by at least 95% of
      prescription dose; and 70, 50, and 30% of bladder and rectum should not receive
      more than 40, 60, and 70% of 81 Gy. SV Volumes ranged from 2.9-30 cc. With two
      course IMRT plans, mean dose to SV was non-uniform and varied between patients by
      48% (54 to 80 Gy). With single-course IMRT plan, mean dose to SV was more uniform
      and varied between patients by only 9.6% (58.2 to 63.8 Gy), to deliver MED of 56
      Gy for alpha/beta - 1. Single course IMRT plan MUs were slightly larger than
      those for two-course IMRT plans, but within the range seen for two-course plans
      (549-959 MUs, n=51). Dose max for single-course plans were similar to two-course
      plans. Doses to PTV, rectum and bladder with single course plans were as per DVC
      and comparable to two-course plans. Single course IMRT plan reduces IMRT planning
      and QA time to half.

PMID- 16981794
TI  - Linac-based intensity modulated total marrow irradiation (IM-TMI).
AB  - Total body irradiation (TBI) has been used as a form of systemic therapy for the
      treatment of hematological malignancies and as a pre-conditioning regimen prior
      to bone marrow transplant. However, standard techniques are associated with both
      acute and chronic toxicities due to the large volumes of normal tissue
      irradiated. Intensity modulated radiation therapy (IMRT), with its ability to
      conform the high dose region to the shape of the target, offers a method to
      reduce radiation related sequelae and potentially allow for the delivery of
      higher than conventional doses. The goal of this study is to investigate the
      feasibility of a linac-based approach to intensity modulated total marrow
      irradiation (IM-TMI) and to discuss the challenges associated with its clinical
      implementation. The successful development of linac-based IM-TMI would represent
      advancement in the field of radiotherapy and potentially reduce the incidence and
      severity of complications associated with current TBI techniques.

PMID- 16981795
TI  - Comparison of 2D vs. 3D dosimetry for Rotte 'Y' applicator high dose rate
      brachytherapy for medically inoperable endometrial cancer.
AB  - The purpose of our research is to compare CT-based volumetric calculations and
      International Commission on Radiation Units and Measurements (ICRU) reference
      point estimates of radiation doses to the target volume, bladder, rectum, and
      sigmoid colon in patients with carcinoma of the endometrium treated with high
      dose rate intracavitary Rotte 'Y' applicator brachytherapy (HDRB). Eleven
      patients with cancer of the endometrium were treated with CT-compatible HDR
      intracavitary Rotte 'Y' applicators (Nucletron) and underwent post-implant pelvic
      CT scans with applicators in place. All patients were treated using orthogonal
      radiography-based planning. The dose was prescribed to uterine point (a point
      located 2 cm below the center of a line drawn between the tips of the two ends of
      the Rotte applicator extending laterally from the tandem by half the maximum
      uterine width), Point A, and 0.5 cm depth along the upper 3 cm vagina. CT-images
      were transferred to the PLATO treatment planning system version 14.2.6 and
      retrospectively planned for volumetric calculations. The clinical target volume
      (CTV) included the entire uterus, cervix, and upper 3 cm of vagina. The volumes
      of organs at risk (OAR) were digitized. Dwell positions were identified and
      registered in both the uterine tandem for each patient. For those receiving HDRB
      alone, the prescribed dose was 7 Gy x 5 fractions. Patients who were treated
      following external beam radiation therapy (EBRT) received 4 Gy x 5 fractions. The
      interfraction interval was 6-8 hours. The DVHs were computed for the CTV,
      bladder, rectum, and sigmoid colon. To compare doses of OARs, 1.0 cc, 2.0 cc, and
      5.0 cc volumes receiving the highest dose were calculated from DVHs. 3D
      optimization was done to improve target coverage and decrease dose to critical
      organs and compared with the 2D orthogonal radiograph-based plan. The mean of
      percentage of prescribed dose +/- S.D to 1 cc, 2 cc, and 5 cc of the OARs of
      interest were as follows: Rectum 44 +/- 21%, 39 +/- 18%, and 33 +/- 15%; bladder
      104 +/- 36%, 91 +/- 31%, and 73.9 +/- 24%; and sigmoid 124 +/- 35%, 109 +/- 30%,
      and 89 +/- 25%, respectively. The corresponding dose to ICRU 38 bladder and
      rectal points were 98 +/- 55% and 50.5 +/- 32%, respectively. The mean dose to
      uterine point and point A were 99 +/- 1.7% and 98 +/- 3%, respectively. The mean
      CTV volume was 160 +/- 89 cc with the percentage of volume getting 100% and 90%
      of the dose being 62 +/- 12% and 68 +/- 12% with 2D plan versus 57 +/- 8% and 67
      +/- 8.9% with 3D plan. The dose to critical organs were reduced with 3D
      optimization for rectum, bladder, and sigmoid by 5.6% (p = 0.04), 20.6% (p =
      0.02), and 26.8% (p = 0.005), respectively. Compared to the 3-D volume dose, the
      prescription points overestimated the dose to the target volume. The under-dosing
      was because of inability of two channel applicator to cover volumes in the region
      of the cervix and vagina. The dose to sigmoid colon was high and attention should
      be given to the sigmoid dose at the time of treatment planning. 3D planning
      helped in reducing the dose to the critical organs without compromising target
      coverage. Correlations with outcome are needed to better define the role of 3D
      dosimetry in treatment planning.

PMID- 16981796
TI  - Frameless stereotactic radiosurgery for recurrent head and neck carcinoma.
AB  - The aim of this study was to assess the feasibility and toxicity of stereotactic
      radiosurgery (CK-SRS) using the CyberKnife Frameless Radiosurgery System (Accuray
      Inc., Sunnyvale, CA) in the management of recurrent squamous cell carcinoma of
      the head and neck region (SCCHN). Between November 2001 and February 2004, 22
      patients with recurrent, previously irradiated SCCHN were treated with CK-SRS.
      The following endpoints were assessed post-CK-SRS: local control (LC), cause
      specific survival (CSS), overall survival (OS), symptom relief, and acute and
      late toxicity. Kaplan-Meier survival analyses were used to estimate the LC, CSS,
      and OS rates. Clinical symptoms were graded as "improved," "stable," or
      "progressed" after CK-SRS. Acute and late toxicity were graded according to the
      National Cancer Institute Common Toxicity Criteria (CTC) scale, version 2.0.
      Seventeen patients were followed until their death. The median follow-up in the
      remaining five patients was 19 months (range 11-40 months). The median survival
      time for the entire cohort was 12 months from the time of CK-SRS. The 2-year LC,
      CSS, and OS rates were 26%, 26%, and 22%, respectively. After CK-SRS, symptoms
      were improved or stable in all but one patient who reported increasing pain. The
      treatment was well tolerated, with one case each of Grade 2 and 3 mucositis.
      There were no acute Grade 4 or 5 CTC toxicities. There were no late toxicities in
      this cohort. Frameless stereotactic radiosurgery for recurrent SCCHN is feasible
      and safe in the setting of high doses of prior irradiation. The majority of
      patients experienced palliation of disease without excess toxicity.

PMID- 16981797
TI  - In vivo tumor imaging in mice using a state-of-the-art clinical PET/CT in
      comparison with a small animal PET and a small animal CT.
AB  - The aim of this prospective study was to assess the feasibility of a state-of-the
      art clinical PET/CT scanner for in vivo tumor imaging in mice in comparison to a
      small animal PET scanner and a small animal CT scanner. Seventeen female NMRI
      nude mice bearing a subcutaneous transplanted murine mammary carcinoma (EMT6) on
      the right hind limb were examined using a clinical PET/CT scanner (biograph
      Sensation 16), a dedicated small animal PET scanner (MOSAIC system), and a
      dedicated small animal CT scanner (MicroCAT II). 18F-fluoroazomycin arabinoside
      (18F-FAZA) was used as PET tracer for imaging of regional tumor hypoxia. The
      examination of tumor-bearing mice using a state-of-the-art clinical PET/CT
      scanner, a dedicated small animal PET scanner and a dedicated small animal CT
      scanner revealed good image quality and allowed the evaluation and correlation of
      molecular/metabolic alterations of cancers with anatomical/morphological
      findings. The tumor lesions showed a 1.89 +/- 0.6 higher mean tumor-to-background
      ratio +/- SD for the dedicated small animal PET scanner than the PET from the
      clinical PET/CT scanner (P<0.001). The mean tumor-to-background ratio of the PET
      of the clinical PET/CT scanner showed a high correlation with the mean tumor-to
      background ratio of the dedicated small animal PET scanner (r2 = 0.92). The
      tissue hypoxia in the subcutaneous transplanted EMT6 tumors did not correlate
      with the tumor volume. Clinical PET/CT scanners are widely available and could
      contribute not only to human clinical routine examinations, but also to tumor
      research in animals. The molecular/metabolic information is reduced when imaging
      small tumors of mice with clinical PET/CT scanners due to the low spatial
      resolution and sensitivity of the PET scanners. The examination of small tumors
      in mice should be reserved to research centers with small animal PET/CT scanners
      because they provide promising hope to achieve accurate measurement of activity
      concentration. For tumor research in humans and animals using clinical PET/CT
      scanners, PET scanners with a higher spatial resolution and a higher sensitivity
      will be highly promising, but will be in competition to PET/MRI.

PMID- 16981798
TI  - Effect of polyethylenimine, a cell permeabilizer, on the photosensitized
      destruction of algae by methylene blue and nuclear fast red.
AB  - The present study reports the effect a cell permeabilizer, polyethylenimine (PEI)
      has on the photodynamic effect of methylene blue (MB) and nuclear fast red (NFR)
      in the presence of hydrogen peroxide (H2O2). The photosensitized destruction of
      the algae Chlorella vulgaris under irradiation with visible light is examined.
      The photodynamic effect was investigated under aerobic and anaerobic conditions.
      The presence of a permeabilizer during the photosensitized destruction of C.
      vulgaris does not enhance the activity of the MB, MB/H2O2 system or the NFR,
      NFR/H2O2 system under aerobic conditions. However under anaerobic conditions we
      have determined that when a cell permeabilizer was added to the MB/H202 system,
      the photosensitized destruction of C. vulgaris proceeded via a combination of
      Type I and Type II mechanisms. The presence of PEI enforces MB/H2O2 to be active
      toward the destruction of C. vulgaris whether oxygen is present or absent. Under
      aerobic and anaerobic conditions the activity of NFR was suppressed in the
      presence of PEI as a result of electrostatic interactions between the
      photosensitizer and the cell permeabilizer. The decrease in fluorescence recorded
      is indicative of destruction of the chlorophyll a pigment.

PMID- 16981799
TI  - Assessing potentially inappropriate prescribing in the elderly Veterans Affairs
      population using the HEDIS 2006 quality measure.
AB  - BACKGROUND: Studies have found that 20% to 25% of older patients receive drugs
      identified as inappropriate by the 1997 Beers criteria. After the addition of 22
      new drugs to the 2003 Beers criteria, the National Committee on Quality Assurance
      convened an expert consensus panel to identify which drugs from the 2003 Beers
      criteria should always be avoided in the elderly. The resulting list of drugs to
      avoid was added to the 2006 Health Plan Employer Data and Information Set (HEDIS)
      to measure the quality of prescribing for the elderly. OBJECTIVE: To use HEDIS
      2006 criteria to determine the rate of potentially inappropriate prescribing in
      the elderly (PIPE) and to determine if patient risk factors are similar to those
      found using Beers criteria. METHODS: This cross-sectional database study
      identified older patients receiving drugs included in the HEDIS 2006 criteria
      using national data from the Veterans Health Administration. Patients aged 65
      years or older on October 1, 1999, with at least 2 outpatient visit days during
      fiscal year 2000, ending September 30, or outpatient visits in fiscal years 1999
      and 2000 were included (N=1,096,361). Multivariable logistic regression analyses
      stratified by gender identified patient characteristics associated with increased
      risk of HEDIS 2006 drug exposure. Since oral estrogens were considered
      appropriate at the time of this study, they were excluded from the list of HEDIS
      2006 drugs. RESULTS: Overall, 19.6% of older veterans were exposed to HEDIS 2006
      drugs. 23.3% of older veteran women and 19.2% of older veteran men. The most
      commonly prescribed HEDIS 2006 drugs were antihistamines (received by 9.0% of men
      and 10.7% of women), opioid analgesics (received by 4.6% of men and 5.8% of
      women), and skeletal muscle relaxants (received by 4.3% of men and 5.3% of
      women). Propoxyphene was the most commonly used HEDIS 2006 drug, received by 4.5%
      of men and 5.7% of women, followed by diphenhydramine, received by 3.5% of men
      and 4.7% of women, and hydroxyzine, received by 3.2% of both men and women.
      Patients receiving 10 or more medications of any type were at greatest risk of
      exposure. Men were 8.2 times more likely to receive at least 1 HEDIS 2006 drug
      than those taking 1 to 3 drugs of any type (95% confidence interval [CI], 8.0
      8.4), while women were 9.6 times more likely (95% CI, 8.2-11.2). CONCLUSIONS:
      Even though we included a slightly different list of drugs to avoid, results for
      the HEDIS 2006 measure were similar to those of the 1997 Beers criteria. The
      HEDIS 2006 drugs are commonly prescribed, and there is a distinct need for direct
      evidence linking HEDIS 2006 PIPE exposure to adverse patient outcomes. To reduce
      PIPE, it seems necessary to provide additional evidence for clinicians through
      the conducting of a well-designed study to assess patient outcomes associated
      with PIPE exposure as defined by the HEDIS criteria.

PMID- 16981800
TI  - Total and component health care costs in a non-Medicare HMO population of
      patients with and without type 2 diabetes and with and without macrovascular
      disease.
AB  - BACKGROUND: Type 2 diabetes (T2DM) is one of the most prevalent and costly
      chronic conditions in the United States. Macrovascular disease (MVD) remains a
      common and costly comorbidity in T2DM. Understanding the impact of MVD on total
      health care costs in patients with T2DM is of great importance to managed care
      organizations (MCOs). OBJECTIVE: To examine from the perspective of an MCO the
      impact of MVD on health care costs in patients with T2DM and in a matched
      comparison group of patients without diabetes. METHODS: This study involved
      retrospective analysis of administrative claims (eligibility, pharmacy, and
      medical) using data from a commercial health maintenance organization population
      of approximately 700,000 members in an East Coast health plan. Patients were
      included in this study if they (a) had 2 or more claims for T2DM ( International
      Classification of Diseases, Ninth Revision, Clinical Modification[ICD-9-CM] codes
      250.X0 or 250.X2), or (b) had a prescription drug claim for insulin and a
      diagnosis of T2DM, or (c) had at least 1 pharmacy claim for an oral glycemic
      modifying agent during the 12-month period from January 1, 2003, through December
      31, 2003. Patients with 2 or more medical claims for type 1 diabetes (ICD-9-CM
      codes 250.X1 or 250.X3) were excluded from the study. A random group of
      comparison patients without diabetes (ICD-9 code 250.xx) were matched on age
      group and sex. Study patients in these 2 groups were subdivided into 4 groups
      based on the presence of medical claims with diagnosis codes for MVD (acute
      myocardial infarction, other ischemic heart disease, coronary artery bypass
      surgery, percutaneous transluminal angioplasty, congestive heart failure,
      cerebrovascular accident, peripheral vascular disease, cerebrovascular disease,
      and peripheral vascular disease). Direct medical costs were aggregated for 12
      months after the index date for patients in all 4 groups. Bootstrapping technique
      was used to compare the health care costs between patients with T2DM and those
      without diabetes, stratified by MVD status. RESULTS: A total of 9,059 patients
      with T2DM were identified and were matched by age group and sex to a random group
      of patients without diabetes. MVD was present in 26.9% (n=2,441) of patients with
      T2DM versus 11.3% (n=1,027) of patients without diabetes. Patients with MVD and
      T2DM were, on average, a year younger than patients with MVD but without diabetes
      (54.55 vs. 55.55 years, P <0.001). Patients with T2DM but without MVD were nearly
      the same age as patients with neither diabetes nor MVD (50.44 vs. 50.59 years,
      P=0.092). The T2DM patients with MVD had average 12-month costs more than 3 times
      the costs for patients with T2DM but without medical claims with diagnosis codes
      for MVD--10,450 dollars versus 3,385 dollars, respectively. Pharmacy costs
      accounted for 29.0% and inpatient hospital costs accounted for 43.9% of total
      medical costs in T2DM patients with MVD versus 55.0% and 17.3%, respectively, in
      T2DM patients without MVD. Patients with MVD diagnoses and T2DM had total average
      medical costs that were 1.7 times the total medical costs for MVD patients
      without T2DM--10,450 dollars versus 6,090 dollars, respectively. CONCLUSIONS: The
      results of this analysis suggest that MVD may triple the total medical care costs
      in patients with T2DM. These economic consequences would appear to support the
      importance of interventions intended to prevent macrovascular events in patients
      with T2DM.

PMID- 16981801
TI  - Review of eight pharmacoeconomic studies of the value of biologic DMARDs
      (adalimumab, etanercept, and infliximab) in the management of rheumatoid
      arthritis.
AB  - BACKGROUND: Treatment options for the management of rheumatoid arthritis (RA)
      have expanded from the traditional disease-modifying antirheumatic drugs (DMARDs)
      to include the biologic DMARDs that inhibit tumor necrosis factoralpha (TNF-a).
      OBJECTIVE: To assess the medical literature for studies of the economic value of
      biologic DMARDs, specifically the 3 TNF-a inhibitors (adalimumab, etanercept, and
      infliximab) used for the management of RA, compared with the traditional DMARDs
      such as sulfasalazine, antimalarials, penicillamine, gold, methotrexate,
      azathioprine, leflunomide, and cyclophosphamide. METHODS: A comprehensive search
      of the MEDLINE and HealthSTAR databases was conducted to identify cost-efficacy,
      cost-effectiveness, or cost-utility studies published in the English language
      (from 1966 through November 2004). The search terms and/or MeSH (medical subject
      headings) titles were cost-benefit analysis, rheumatoid arthritis, antirheumatic
      agents, antineoplastic and immunosuppressive agents. Studies were critically
      reviewed and quality was assessed using the Quality of Health Economic Studies
      instrument. Most studies evaluated the use of biologics among RA patients
      resistant to DMARDs. Studies were assessed with regard to comparators evaluated,
      measures of efficacy, perspectives, model duration, treatment duration, and
      discount rate. RESULTS: From 180 titles identified, 155 were excluded for the
      following reasons: 89 because they did not consider the drugs of interest, 15
      because the population was not RA, 19 because of having the wrong drugs and
      population, 22 because they were review articles, and 10 because they were
      general articles. Twentyfive abstracts were accepted for further review. Of
      these, 13 abstracts were subsequently selected for full-text review. One of the
      authors identified a study not indexed in MEDLINE. Ultimately, 2 cost
      effectiveness and 6 cost-utility studies were selected for this critical review.
      One study over 6 months reported that triple therapy with DMARDs (methotrexate
      hydroxychloroquine-sulfasalazine) was cost effective for methotrexate-resistant
      patients, which is consistent with American College of Rheumatology (ACR)
      guidelines that support the use of triple therapy prior to biologics. The
      incremental cost-effectiveness ratio (ICER) was $1,500 per patient to achieve an
      ACR20 response for this triple therapy compared with no second-line agent.
      Overall, biologic therapies cost considerably more than traditional DMARDs but
      produced more quality-adjusted life-years (QALYs). Despite differences in design
      and assumptions, published economic models consistently reported ICERs <50,000
      dollars per QALY gained for biologics compared with traditional DMARDs, although
      ICERs of >100,000 dollars were reported from sensitivity analyses. CONCLUSIONS:
      Clinical guidelines currently recommend the use of biologics as step therapy
      after failure of traditional DMARDs. Reported ICERs comparing biologics with
      traditional DMARDs are within a range that is comparable with other accepted
      medical interventions. The worth of the additional expenditure will ultimately be
      judged by formulary and policy decision makers because no maximum cost has been
      defined. Models can be used to inform decision makers, but they must be
      interpreted and applied carefully. More research is also needed to differentiate
      the relative economic value of the various biologic agents by therapeutic
      indication.

PMID- 16981802
TI  - Pharmacy benefit spending on oral chemotherapy drugs.
AB  - BACKGROUND: Pharmacy benefits have historically excluded injectable drugs,
      resulting in coverage of injectable drugs under the medical benefit. High-cost
      biologics and other new drug therapies are often injectables and therefore have
      not presented cost threats to pharmacy benefits. The U.S. Food and Drug
      Administration approval of capecitabine, an oral form of fluorouracil, in 1998,
      and imatinib mesylate in oral dose form for chronic myeloid leukemia, in 2001,
      signaled a new period in budget forecasting for pharmacy benefits, particularly
      for small, self-insured employers for whom a drug with a cost of 25,000 dollars
      per year of therapy for 1 patient could increase total pharmacy benefit costs by
      10% or more. OBJECTIVE: To quantify the actual relative costs of the oral
      chemotherapy drugs in pharmacy benefits in 2006 and identify the history of
      spending on oral chemotherapy drugs relative to total pharmacy benefit spending
      for small, self-insured employers over the 4.5 years through May 2006. METHODS:
      Administrative pharmacy claims from the database of a pharmacy benefits manager
      (PBM) for approximately 500,000 members of small, self-insured employer plans
      were used to calculate the net plan cost of oral chemotherapy drugs relative to
      total drug benefit costs for the period January 1, 2002, through May 31, 2006.
      Current costs for oral chemotherapy drugs for small employers were compared with
      an insured health plan of approximately the same number of members for dates of
      service January 1, 2006, through May 31, 2006. RESULTS: This descriptive analysis
      found that oral chemotherapy drugs represented 0.27% of total drug benefit costs,
      or approximately 0.08 dollars per member per month (PMPM) for small, self-insured
      employers in 2002, rising linearly to 0.73%, or approximately 0.24 dollars PMPM
      in the first 5 months of 2006. Members in pharmacy benefit plans sponsored by
      small employers paid an average 6.9% cost share for oral chemotherapy drugs in
      2006, nearly identical to the average 8.5% paid by members of an insured health
      plan of similar size in total membership, versus 26.9% average cost share for all
      drugs. Imatinib mesylate accounted for 45% of total spending on oral chemotherapy
      agents in 2002 versus 40% in 2006. CONCLUSION: Spending on oral chemotherapy
      drugs as a proportion of total pharmacy benefit costs has more than doubled, from
      about 0.3% in 2002 to 0.7% in 2006. For small, self-insured employers, this
      represents a nearly 3-fold increase in spending, from about 0.08 dollars PMPM in
      2002 to about 0.24 dollars PMPM in 2006.

PMID- 16981803
TI  - PPIs are therapeutically interchangeable and ideal for a managed care
      intervention such as therapeutic MAC.

PMID- 16981804
TI  - Employers need to have a wider horizon than drug costs alone when considering the
      implementation of health care intervention programs.

PMID- 16981805
TI  - What are incretins, and how will they influence the management of type 2
      diabetes?
AB  - OBJECTIVE: To review the pathophysiology of type 2 diabetes (T2DM), the role of
      incretins, the potential of incretin-based therapies to address unmet therapeutic
      needs in T2DM, and the potential impact this will have on the contribution of
      managed care pharmacy to diabetes therapy. SUMMARY: Diabetes, the fifth leading
      cause of death by disease in the United States, costs approximately $132 billion
      per year in direct and indirect medical expenses. According to the Centers for
      Disease Control and Prevention.s National Health and Nutrition Examination
      Survey, a majority of diabetes patients do not achieve target A1C levels with
      their current treatment regimens. Advances in understanding the pathophysiologic
      abnormalities underlying the metabolic dysfunctions associated with T2DM are
      leading to the development of new treatment approaches and new therapeutic
      classes of drugs. Novel incretin-based therapies currently available, and in late
      stage development, are among those showing the greatest promise for addressing
      the unmet needs of traditional therapies.

PMID- 16981806
TI  - Residential treatment for youth: introduction and a cautionary tale.
AB  - This special issue addresses an area in child and adolescent mental health which
      has suffered from significant neglect, that of residential treatment. Though the
      American Orthopsychiatric Association contributed to the development of the
      principles of residential treatment fifty years ago, we find ourselves in the
      midst of a national crisis on how this level of care is implemented in the field.
      This article summarizes the major themes of the special issue, as well as reports
      on the editor's cautionary experience with major problems in one residential
      facility.

PMID- 16981807
TI  - Residential treatment of children and adolescents: past, present, and future.
AB  - This paper reviews the history of residential treatment, examines the central
      concepts that define the therapeutic modality, and shows how those concepts
      provide means of addressing criticisms that have been raised about it in the past
      and adapting residential programs to meet challenges facing them in the future.

PMID- 16981808
TI  - Unlicensed residential programs: the next challenge in protecting youth.
AB  - Over the past decade in the United States, the number of private residential
      facilities for youth has grown exponentially, and many are neither licensed as
      mental health programs by states, nor accredited by respected national
      accrediting organizations. The Alliance for the Safe, Therapeutic and Appropriate
      use of Residential Treatment (A START) is a multi-disciplinary group of mental
      health professionals and advocates that formed in response to rising concerns
      about reports from youth, families and journalists describing mistreatment in a
      number of the unregulated programs. This article summarizes the information
      gathered by A START regarding unregulated facilities. It provides an overview of
      common program features, marketing strategies and transportation options. It
      describes the range of mistreatment and abuse experienced by youth and families,
      including harsh discipline, inappropriate seclusion and restraint, substandard
      psychotherapeutic interventions, medical and nutritional neglect, rights
      violations and death. It reviews the licensing, regulatory and accrediting
      mechanisms associated with the protection of youth in residential programs, or
      the lack thereof. Finally, it outlines policy implications and provides
      recommendations for the protection of youth and families who pursue residential
      treatment.

PMID- 16981809
TI  - Hope as an outcome variable among youths in a residential care setting.
AB  - This study investigated changes in hope among 155 youths (ages 10 to 17 years)
      placed in a residential treatment facility over a 6-month period. The child and
      adolescent participants met criteria for a range of emotional and behavioral
      disorders and received interventions hypothesized to improve hopeful thinking.
      Hope scores significantly improved over 6 months of treatment. The positive
      changes in hope were not moderated by ethnicity or sex. For Agency hope scores
      (i.e., willpower), those with higher levels of psychopathology at admission
      demonstrated significantly more improvement in agency thinking over the course of
      6 months.

PMID- 16981810
TI  - Gender differences in adolescents in residential treatment.
AB  - Gender differences for adolescents in residential care were examined for a sample
      of 2,067 youths in a large residential facility. At admission, female youths were
      more troubled than male youths, as shown in significantly higher Diagnostic
      Interview Schedule for Children (DISC) diagnoses and comorbidity rates, higher
      internalizing and externalizing Child Behavior Checklist scores, and
      significantly higher Suicide Prevention Scale hopelessness, negative self
      evaluation, and suicide ideation scores. Girls had higher rates of depressive and
      anxiety diagnoses on the DISC at both admission and 1 year. Both genders
      demonstrated significant reductions in both externalizing and internalizing
      problem behaviors over the first year in the program. Girls had significantly
      higher rates of internalizing problem behavior but showed a significantly greater
      reduction in these behaviors than did boys. At departure, girls were rated as
      being more successful than boys by clinical staff. Youths did not differ by
      gender in their behavior on a 6-month follow-up success scale. Implications for
      prioritizing research addressing the needs of female adolescents in residential
      care are discussed.

PMID- 16981811
TI  - Attachment representations of institutionalized adolescents and their
      professional caregivers: predicting the development of therapeutic relationships.
AB  - This study prospectively examined the effects of adolescent (N=81) and
      professional caregiver (N=33) attachment representations, measured using the
      Adult Attachment Interview, on therapeutic relationships in a youth treatment
      institution. After the first 3 months of the clients' stay in the institution, no
      effects of adolescents' or mentors' (i.e., the professional caregiver assigned)
      security and type of attachment representations were found. In a subgroup of 28
      clients staying for a longer period, more secure adolescents were perceived by
      their mentors as increasing their secure base use and decreasing avoidance of
      contact, whereas more secure mentors were increasingly perceived as available as
      a secure base. Moreover, specific combinations of attachment representations of
      mentor and adolescent had different effects on adolescent hostility.

PMID- 16981812
TI  - Trauma and posttraumatic stress disorder symptomatology: patterns among American
      Indian adolescents in substance abuse treatment.
AB  - In this study the authors examined the prevalence and correlates of posttraumatic
      stress disorder (PTSD) and trauma symptomatology among a sample of 89 American
      Indian adolescents in a residential substance abuse treatment program. These
      youths reported an average of 4.1 lifetime traumas, with threat of injury and
      witnessing injury being most common; molestation, rape, and sexual attack were
      least common. Approximately 10% of participants met the Diagnostic and
      Statistical Manual IV Text Revision (DSM-IV-TR) criteria for full PTSD, and about
      14% met the criteria for subthreshold PTSD. Molestation (including rape and
      sexual attack), experiencing 6 or more traumas, and a diagnosis of abuse of or
      dependence on stimulants were significantly associated with PTSD. Findings
      indicated that trauma was a pervasive phenomenon among this population, with
      sexual traumas being particularly stigmatizing, resulting in high rates of
      posttraumatic symptomatology, specifically PTSD.

PMID- 16981813
TI  - Psychological distress and well-being of Latina and non-Latina White mothers of
      youth and adults with an autism spectrum disorder: cultural attitudes towards
      coresidence status.
AB  - This article examined the emotional well-being of 108 Latina and non-Latina White
      mothers who were coresiding with a youth or adult with an autism spectrum
      disorder (ASD). It was hypothesized that Latina mothers would be more satisfied
      with coresidence than non-Latina White mothers, and that satisfaction with
      coresidence would mediate the relationship between ethnicity and outcomes. When
      controlling for demographic characteristics, non-Latina White mothers were more
      distressed and had lower levels of psychological well-being than Latina mothers.
      As hypothesized, satisfaction with coresidence mediated this difference.
      Qualitative analysis revealed that both groups of mothers valued family cohesion
      as a positive aspect of coresidence. However, Latina mothers were less likely to
      report negative aspects of coresidence than non-Latina White mothers.

PMID- 16981814
TI  - Placement into foster care and the interplay of urbanicity, child behavior
      problems, and poverty.
AB  - Child welfare involvement is related to involvement with poverty, but the
      dimensions of that relationship have not been fully explored. Data from the
      National Survey of Child and Adolescent Well-Being were used to test the
      relationship between poverty indicators and placement into foster care. Poverty,
      ages of children, urban or nonurban settings, and the presence of mental health
      disorders interact to contribute to placement decisions. In urban areas, poverty
      is strongly associated with involvement with child welfare services, but
      children's mental health problems are not. In nonurban areas, children's mental
      health problems are a far greater contributor to child welfare involvement than
      poverty. Implications for understanding the dual functions of child welfare
      placements are provided. Child welfare services continue to address the needs of
      families with children with substantial behavioral problems--yet, federal child
      welfare policy includes no recognition of this important role.

PMID- 16981815
TI  - Who uses consumer-run self-help organizations?
AB  - A multisite evaluation of community mental health services is used to answer two
      questions: (a) How do diagnosis, functioning, and self-assessments of
      consumer/survivor initiative (CSI) and assertive community treatment (ACT)
      participants compare?, and (b) What other supports/services are CSI and ACT
      participants using? The sample is from an Ontario evaluation of consumer/survivor
      peer initiatives in four communities (n=73). The reference group is new (n=48)
      and ongoing (n=134) clients of four ACT teams. Self-help organizations are
      serving a broader population of individuals who include a significant subgroup of
      persons with severe mental illness along with others with a mixed picture of
      higher functioning and greater instability. There is little overlap in the use of
      these modes of service delivery, which suggests that maintaining options within
      systems of care is critical to ensuring coverage and access for the broader
      population.

PMID- 16981816
TI  - Racial differences in social support: kin versus friends.
AB  - Social support was examined among 290 Black and White women recruited from the
      community. We hypothesized that (1) social support, adjusted for social class,
      would not vary by race and (2) social support would be related to well-being.
      Standardized measures were administered, examining support provided by friends
      versus kin separately. Multivariate models showed that Black women reported
      similar numbers of kin and fewer friends than Whites, while satisfaction with
      support did not vary by race. Measures of social support were generally
      associated with well-being. These findings question earlier reports that Black
      women have stronger kin support than White women, suggesting that clinicians
      should not assume that Blacks can rely on kin for social support.

PMID- 16981817
TI  - Generational, ethnic, and national differences in attitudes toward the rights of
      children in Israel and Palestine.
AB  - With the nearly universal ratification of the Convention on the Rights of the
      Child, children's rights have become a cornerstone of discussions in relation to
      human rights and human services around the world. Although the concept of
      children's rights is now broadly established, the meaning of this concept and its
      significance for policies and programs are apt to vary across nations, cultures,
      religions, and age groups. With the close proximity of diverse national, ethnic,
      and religious groups and seemingly omnipresent political conflicts about the
      meaning of rights among them, the Middle East presents unusual opportunities to
      understand the effects of such variables on attitudes toward children's rights.
      Drawing from samples of Jews from Israel, Palestinian Muslims from Israel, and
      Palestinian Muslims from the Palestinian Authority, surveys were conducted of
      adolescents, young mothers (mothers of toddlers), middle-aged mothers (mothers of
      adolescents), and grandmothers. Attitudes toward children's rights were more
      strongly affected by the respondents' ethnicity and nationality than by their
      age.

PMID- 16981818
TI  - Family influences and biologically confirmed sexually transmitted infections
      among detained adolescents.
AB  - Data from a convenience sample of 476 detained adolescents were used to examine
      the relationship between family influences and biologically confirmed sexually
      transmitted diseases (STDs). Results indicated that frequent parental monitoring
      was negatively associated with STD infection and that this relationship was
      modified by age, gender, and race. Findings suggest that STD prevention efforts
      for detained adolescents (particularly high-risk minority females older than age
      16) might focus on increasing monitoring by a parent or parental figure.

PMID- 16981819
TI  - Mental health in adolescence: is America's youth flourishing?
AB  - A continuous assessment and a categorical diagnosis of the presence of mental
      health, described as flourishing, and the absence of mental health, characterized
      as languishing, are proposed and applied to data from the second wave of the
      Child Development Supplement (CDS-II) of the Panel Study of Income Dynamics
      (PSID), in which a comprehensive set of subjective well-being items were
      administered to a sample of 1,234 youth ages 12-18. Flourishing was the most
      prevalent diagnosis among youth ages 12-14; moderate mental health was the most
      prevalent diagnosis among youth ages 15-18. Depressive symptoms decreased as
      mental health increased. Prevalence of conduct problems (arrested, skipped
      school, alcohol use, cigarette smoking, and marijuana use) also decreased and
      measures of psychosocial functioning (global self-concept, self-determination,
      closeness to others, and school integration) increased as mental health
      increased. Findings suggest the importance of positive mental health in future
      research on adolescent development.

PMID- 16981820
TI  - Target validation in silico: does the virtual patient cure the pharma pipeline?
AB  - Genomics has multiplied the number of targets for new therapeutic interventions,
      but this has not yet lead to a marked increase of pharma pipeline outputs. The
      complexity of protein function in higher order biological systems is often
      underestimated. Translation from in vitro and in vivo results to the human
      setting frequently fails due to unforeseen toxicity and efficacy issues.
      Biosimulation addresses these issues by capturing the complex dynamics of
      interacting molecules and cells in mechanistic, predictive models. A central
      concept is that of the virtual patient, an encapsulation of a specific
      pathophysiological behaviour in a biosimulation model. The authors describe how
      virtual patients are being used in target identification, target validation and
      clinical development, and discuss challenges for the acceptance of biosimulation
      methods.

PMID- 16981821
TI  - Epidermal growth factor receptor-targeted molecular therapeutics for head and
      neck squamous cell carcinoma.
AB  - Several molecular-targeted therapeutics have been tested in clinical trials for
      the treatment of head and neck squamous cell carcinoma (HNSCC). Of these,
      therapeutics targeting the epidermal growth factor receptor (EGFR) have been
      studied most extensively and some agents have demonstrated measurable clinical
      effectiveness. However, molecular studies designed to define HNSCC patient
      subcohorts of likely responders to EGFR-targeted therapy have not identified
      molecular signatures that correlate with clinical response. Here, the authors
      summarise the relevant clinical findings and highlight reported molecular
      correlative studies for EGFR-targeted therapeutics for HNSCC. The authors focus
      especially on molecular markers evaluated for association with clinical response
      and include data from EGFR-targeted clinical studies in other cancer sites that
      they anticipate will be of interest to the head and neck cancer research and
      treatment communities.

PMID- 16981822
TI  - The therapeutic potential of CD39: interview with Dr Simon Robson by Emma
      Quigley.
AB  - Dr Simon C Robson (Harvard University) was interviewed by Emma Quigley
      (Commissioning Editor, Expert Opinion) on 14th August 2006. Born in the UK, Dr
      Simon Robson obtained his MB, ChB from the University of Cape Town, South Africa
      in 1978 and his PhD in Immunology in 1989. He worked in both South Africa and the
      UK before moving to the USA in 1994. Now an Associate Professor in Medicine at
      Harvard University, Dr Robson is conducting research dealing with the vascular
      biology of transplantation and specifically focussing on how endothelial and
      immune cell purinergic signalling is modulated by ecto-nucleotidases of the CD39
      family (ecto-enzymes that hydrolyse extracellular nucleotides to generate
      nucleosides). In several studies funded by the NIH, ROTRF and other agencies, Dr
      Robson has been researching genomics, proteomics and the biology of CD39 in
      models of inflammation and immunity. Dr Robson has published > 200 papers and is
      on the Editorial Boards of many well-respected journals, including Expert Opinion
      on Therapeutic Targets.

PMID- 16981823
TI  - Targeting the CB2 receptor for immune modulation.
AB  - Early work on the biology of the components of Cannabis sativa showed evidence
      for a potential influence on immune regulation. With the discovery of a
      peripheral cannabinoid receptor associated with immune cells, many laboratories
      have sought to link the immunoregulatory activities of cannabinoid compounds with
      this receptor, hoping that such compounds would lack the psychoactive effects of
      marijuana and other nonspecific cannabinoid agonists. In this report, the authors
      investigate the role of the cannabinoid CB2 receptor in immune regulation, with
      particular emphasis on compounds shown to regulate immune cell recruitment. The
      authors conclude by using the immune cell recruitment model to rationalise
      cannabinoid CB2 receptor-specific effects in modulating immune disease,
      particularly the increasing evidence for its role in experimental autoimmune
      encephalomyelitis and in influencing bone density.

PMID- 16981824
TI  - Current strategies for the treatment of Alzheimer's disease and other
      tauopathies.
AB  - The pathological hallmarks of Alzheimer's disease (AD) include abnormal intra-
      and extraneuronal tau and amyloid accumulation, respectively, accompanied by
      gliosis, oxidative stress and neuron loss. The discovery of mutations within the
      tau gene itself that cause clinical dementia (i.e., fronto-temporal dementia with
      Parkinsonism linked to chromosome 17 [FTDP17]) demonstrated that disruption of
      normal tau function independent of amyloidogenesis was sufficient to cause
      neuronal loss and clinical dementia. These studies demonstrate the need for
      therapeutics that either decrease the total pool of tau or selectively reduce
      aberrant forms of tau (i.e., hyperphosphorylated, misfolded etc.). To this point,
      therapeutic development for tauopathies, including AD, have primarily focused on
      either the phosphorylation of tau, as it is a downstream target for many kinases
      and signalling cascades, or inhibition of tau aggregation. Recent developments,
      however, suggest that pharmacological targeting of other mechanisms may hold
      therapeutic promise for the treatment of tauopathies.

PMID- 16981825
TI  - Phosphodiesterase 4D and heart failure: a cautionary tale.
AB  - Stimulation of several G-protein-coupled receptors (GPCRs) promotes intracellular
      production of cyclic adenosine 3',5'-monophosphate (cAMP) and subsequently
      activates protein kinase A (PKA). In the heart, beta-adrenergic receptor (beta
      AR) stimulation increases contractile performance and heart rate as part of the
      'fight-or-flight' stress response. Molecular organisation of PKA-effector
      association occurs by A kinase anchoring proteins (AKAPs), which target kinase
      action to specific intracellular sites. Some AKAPs interact directly with
      specific cAMP-hydrolysing phosphodiesterase (PDE) isoforms allowing for the
      assembly of multi-protein complexes that create focal points of intracellular
      cAMP signalling. Certain PDE isoforms co-localise with PKA as part of negative
      feedback mechanisms which may protect from excess beta-AR stimulation of Ca2+
      transporters during cardiac excitation-contraction coupling. Pharmacological PDE
      inhibition increases intracellular cAMP concentrations and augments excitation
      contraction coupling in heart failure. However, chronic PDE inhibitor treatment
      causes severe cardiac side effects and increases mortality. Moreover, cAMP
      hydrolysing PDE activity was found decreased in heart failure which may
      contribute to disease progression via chronic PKA-dependent dysregulation of Ca2+
      transport proteins. The authors review the contribution of PDE activity in the
      heart to contractile stress adaptation, the significance of altered cAMP
      signalling in heart failure, and the effects of PDE inhibition in heart disease.

PMID- 16981826
TI  - The role of nitric oxide in mediating tumour blood flow.
AB  - Nitric oxide (NO) is a ubiquitous molecule with a myriad of physiological and
      pathophysiological roles. It has numerous direct and indirect effects on tumour
      vasculature as both a regulatory and effector molecule. NO affects tumour blood
      flow through its effects on tumour angiogenesis, vascular tone and vascular
      permeability, partly via its interaction with vascular endothelial growth factor.
      In this review, the authors examine the basic tenants of NO biology, the
      association of NO with tumour progression, and the role NO plays in mediating
      alterations in vascular functions in tumours.

PMID- 16981827
TI  - Targeting caspase 8 to reduce the formation of metastases in neuroblastoma.
AB  - The clinical challenge in neuroblastoma is the presence of metastasis at
      diagnosis in the majority of patients. Caspase 8 is an integral protein in death
      receptor-associated apoptosis, and loss of caspase 8 via the epigenetic
      phenomenon of methylation in neuroblastoma has led to increased resistance to
      chemotherapy. Recent evidence suggests that caspase 8 loss may also contribute to
      a metastatic phenotype; thus, caspase 8 may prove to be an attractive target for
      therapy both in treating primary tumours as well as preventing and treating
      metastatic lesions. Numerous methods have been described to manipulate caspase 8
      levels both in vitro and in vivo, and investigation into caspase 8 isoforms may
      also bring forth additional therapeutic targets.

PMID- 16981828
TI  - Is caveolin-1 a viable therapeutic target to reduce cancer metastasis?
AB  - Caveolin-1 is the major structural protein in caveolae; small Omega-shaped
      invaginations within the plasma membrane. Caveolae are involved in signal
      transduction, wherein caveolin-1 acts as a scaffold to organise multiple
      molecular complexes regulating a variety of cellular events. Caveolin-1 has both
      tumour suppressor and oncogenic activities. However, recent evidence suggests a
      role for caveolin-1 in promoting cancer cell migration and metastasis with both
      loss and overexpression of caveolin-1 being described as a marker for progression
      in a variety of tumour types. Further studies are beginning to determine the
      molecular mechanisms by which caveolin-1 acts in promoting a metastatic
      phenotype. Targeting caveolin-1 expression may present a novel means of
      preventing metastasis. The purpose of this review is twofold: firstly, to survey
      the current knowledge of the contribution of caveolin-1 in promoting a
      metastasis, and secondly, to explore the viability of targeting caveolin-1 with
      novel therapeutics.

PMID- 16981829
TI  - A ubiquitous membrane fusion protein alpha SNAP: a potential therapeutic target
      for cancer, diabetes and neurological disorders?
AB  - Alpha soluble NSF attachment protein (alphaSNAP) is a ubiquitous and
      indispensable component of membrane fusion machinery. Deletion of alphaSNAP is
      embryonically lethal. Yet, there is accumulating evidence that milder alterations
      in expression levels of alphaSNAP may be associated with a number of specific
      pathological conditions, such as several neurological disorders, Type 2 diabetes
      and aggressive neuroendocrine tumours. Here, the authors review the evidence
      available for animal models and for humans, and discuss possible therapeutic
      approaches that may target alphaSNAP.

PMID- 16981830
TI  - The vitamin D receptor as a therapeutic target.
AB  - The vitamin D receptor (VDR) is a member of the large family of nuclear receptor
      transcription factors and specifically binds the micronutrient-derived hormone
      1alpha,25(OH)2D3. A central endocrine role for this receptor in bone health was
      established at the beginning of the 20th century. Over the last 25 years,
      additional roles, perhaps through autocrine and paracrine mechanisms, have been
      established for VDR to regulate cell proliferation and differentiation, and more
      recently to exert immunomodulatory and antimicrobial functions. These findings,
      from in vitro and in vivo experiments, have generated considerable interest in
      targeting the VDR in multiple therapeutic settings. As with many potential
      therapeutics, it has also become clear that cells and tissues may also display de
      novo and acquired mechanisms of resistance to these actions. Consequently, a
      range of experimental and clinical options are being developed to bring about
      more targeted actions, overcome resistance and enhance efficacy of VDR-centred
      therapeutics.

PMID- 16981831
TI  - The fatty acid oxidation pathway as a therapeutic target for insulin resistance.
AB  - It is recognised that obesity is a major driver for insulin resistance and Type 2
      diabetes in both adult and young members of diverse societies. Weight loss
      strategies involving diet, exercise and behaviour modification work only for the
      minority of highly motivated individuals, but fail completely in the vast
      majority; yet weight loss is associated with benefits in metabolic health. Why is
      it so difficult to maintain weight loss in the longer term? Here, the authors
      explore the possibility that energy partitioning, especially of lipids, plays a
      key role in both weight recidivism and, by association, insulin resistance. Drug
      targets that address key pathways important in this process, where progress in
      drug discovery is apparent, are discussed.

PMID- 16981832
TI  - Heat-shock proteins: new keys to the development of cytoprotective therapies.
AB  - As molecular chaperones, heat-shock proteins (HSPs) function to limit protein
      aggregation, facilitate protein refolding and chaperone other proteins. Under
      conditions of cellular stress, intracellular HSP levels increase in order to
      provide cellular protection and maintain homeostasis. Evidence exists that the
      HSP family may be secreted into the circulation via lipid raft-mediated, granule
      mediated or exosome-mediated exocytosis in haematopoietic and tumour cells.
      Extracellular HSPs exert immunomodulatory activities and play an important role
      in innate immune activation against pathogen infection. Membrane-bound Hsp70 in
      tumour cells or released chaperone-tumour associated antigen complex represent a
      target structure for the cytolytic attack by natural killer cells or T
      lymphocytes. Cellular stresses induce stress granule formation to evade
      detrimental cellular effects, mediating preconditioning phenotype. Therefore,
      induction of cellular stress tolerance by preconditioning (e.g., heat shock)
      might be potential therapeutic targets.

PMID- 16981833
TI  - Novel targets in pancreatic cancer: focus on future paths to therapy.
AB  - This clinical science symposium at ASCO 2006, co-chaired by Drs Barbara Burtness
      (Fox Chase Cancer Center, USA) and Christophe Louvet (Hopital Saint Antoine,
      France), focused on the evaluation of new targets for treatment of pancreatic
      cancer. Pancreatic cancer is a devastating tobacco-related malignancy, with >
      33,000 new cases expected in 2006 and a nearly equal number of deaths. Cytotoxic
      therapy has had little impact on a dismal overall survival in advanced disease of
      6 months. Thus, the development of new therapeutics is critical. As the number of
      novel targeted therapeutics increases, the ability to design and conduct rational
      clinical trials will be of paramount importance. The presentations focused on
      preclinical model systems to evaluate new therapeutics for clinical testing, a
      laboratory analysis of the role of tissue factor in pancreatic cancer
      pathogenesis, and clinical data evaluating dual epidermal growth factor
      receptor/Her2 inhibition.

PMID- 16981834
TI  - Novel targets in prostate cancer.
AB  - Despite recent advances in the understanding of the cellular and molecular
      biology of prostate cancer, new options for the treatment of prostate cancer
      remain elusive. Targeted therapies have shown promising activities in many solid
      tumours and the growing number of targets and targeted agents is creating
      numerous opportunities for clinical research in advanced prostate cancer. At ASCO
      2006 in Atlanta, a clinical science symposium on novel targets in prostate cancer
      was presented. It consisted of three abstracts, each of which was followed by a
      discussant who reviewed the work and placed it in the overall context of current
      approaches to treating prostate cancer. The three abstracts were a discussion of
      a new method for quantification of the androgen receptor; the impact of high-dose
      vitamin D plus chemotherapy on hormone refractory disease and on the risk of
      thromboembolic disease; and the paradoxical effects seen with the raf-kinase and
      vascular endothelial growth factor inhibitor sorafenib, which produced
      improvement in bone scans in the absence of any prostate-specific antigen
      responses.

PMID- 16981835
TI  - The mind-brain relation and neuroscientific foundations: III. Brain and
      psychopathology, the split brain, and dreaming.
AB  - In addition to the findings of neuroscientific research on brain function,
      reviewed in the previous articles (Meissner, 2006a, 2006b), contemporary findings
      relevant to the mind-brain relation derive also from the study of the underlying
      patterns of brain dysfunction related to various forms of psychopathology. Other
      information derives from study of split-brain conditions and from research on
      dream processes and their relation to brain mechanisms. Review of these research
      findings casts further light on aspects of the mind-brain relation and further
      substantiates a unified theory of mind-brain integration.

PMID- 16981836
TI  - Increasing executive and "self-soothing" capacities in the treatment of addictive
      disorders.
AB  - Freud noted many years ago (1917/1963, 1933/1964) that the talking cure was
      developed due to the rather primitive nature of neuroscientific knowledge with
      regard to the brain and hence might eventually be made unnecessary or irrelevant
      by subsequent discoveries of the neuropsychological causation of neurotic
      symptoms. The opposite may be true, however. These discoveries may validate the
      potential effectiveness of therapeutic work with a wide variety of difficult
      personality disorders and addictive forms of pathology. The recent work of
      neuroscientists such as Barkley, Davidson, Goldberg, Schore and Volkow and Fowler
      may allow for empirical demonstrations of benign changes in brain functions
      following an effective course of treatment.

PMID- 16981837
TI  - Borderline personality organization and dissociation.
AB  - The relationship between Kernberg's psychodynamic model of personality
      organization (PO) and dissociation has not yet been explored. Seventy-two
      nonclinical subjects and 222 psychiatric patients completed the Dissociative
      Experiences Scale and the Inventory of Personality Organization. Its Reality
      Testing subscale emerged as the most important predictor for all facets of
      dissociation. Discussing our results in the framework of Fonagy and coworkers'
      model of mentalization, we suggest that dissociation may reflect the preoedipal
      "pretend" mode of psychic functioning while impaired reality testing and
      psychotic experiences might be indicative of the "psychic equivalent" mode.

PMID- 16981838
TI  - Family functioning in the caregivers of patients with dementia: one-year follow
      up.
AB  - Caregivers for relatives with dementia can maintain their quality of life without
      specific intervention. It is unclear which variables are protective and which
      variables are aggravating for the caregiver. To assess the impact of family
      functioning on caregiver burden over time, the authors had caregivers of out
      patients with dementia complete self-report questionnaires at recruitment and at
      1 year. At recruitment, 63% of caregivers were female, with a mean age of 62
      years. Mean patient age was 73 years. The average number of caregiving years was
      3.1. Caregivers were more likely to be spouses (61%). After 1-year, caregivers
      who stayed in the study reported no change in burden, reward, quality of life, or
      overall family functioning, although the patient's activities of daily living and
      level of disability were perceived to have significantly deteriorated. Caregivers
      who reported poor family functioning at initial assessment had higher ratings of
      strain and burden.

PMID- 16981839
TI  - Therapist-client five-factor personality similarity: a brief report.
AB  - A five-factor personality inventory and other measures were administered to 39
      clients and 15 therapists. Global therapist-client personality similarity and
      client neuroticism were moderately to strongly associated with lower symptoms.
      For female clients, global personality similarity and client extraversion were
      moderately associated with therapeutic alliance. These preliminary results
      warrant further investigation. If results are replicated, intake personality
      matching may lead to decreased premature terminations and better outcomes in many
      kinds of psychosocial treatments.

PMID- 16981841
TI  - New study provides comprehensive view of breast cancer gene mutations in the US
      population.

PMID- 16981842
TI  - HLA-B locus in Caucasian patients with carbamazepine hypersensitivity.
AB  - BACKGROUND: A strong pharmacogenetic association has been reported in Chinese
      patients between human leukocyte antigen (HLA)-B*1502 and carbamazepine (CBZ)
      induced Stevens-Johnson syndrome (SJS). METHODS: We have genotyped the HLA-B
      alleles in 56 Caucasian patients with varying severities of CBZ hypersensitivity
      and 43 controls on CBZ without adverse effects. RESULTS: None of our patients
      (including two with blistering skin rashes) were positive for the HLA-B*1502
      allele. HLA-B*0702 allele may protect against severe CBZ hypersensitivity but
      warrants further study. Of secondary interest, the correlation between HLA-B*0801
      and HLA-DR3, DQ2 and TNF -308 alleles (on the ancestral haplotype 8.1) is
      consistent with our previous findings. CONCLUSION: HLA-B*1502 does not seem to be
      a marker for all forms of CBZ-induced hypersensitivity in a Caucasian population.

PMID- 16981843
TI  - Cigarette smoking, N-acetyltransferase genes and the risk of advanced colorectal
      adenoma.
AB  - BACKGROUND: Cigarette use is associated with greater risk for colorectal adenoma,
      a colorectal cancer precursor. N-acetyltransferases, NAT1 and NAT2, are important
      enzymes involved in the metabolism of aromatic amine carcinogens present in
      cigarette smoke. Our interest is in the polymorphisms within the NAT1 and NAT2
      genes that influence the tobacco-colorectal tumor relationship by impacting on
      the metabolic activation and detoxification of tobacco smoke-derived carcinogens.
      METHODS: In the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening
      trial, we compared NAT1 and NAT2 gene variant distributions for 772 cases with
      left-sided advanced adenoma and 777 gender and age-matched controls. Individual
      NAT1 and NAT2 diplotypes were assigned and NAT2 acetylator phenotypes were
      derived. RESULTS: Risks for advanced colorectal adenoma were significantly
      increased among recent smokers (current smokers or those who quit less than 10
      years ago) (odds ratio [OR] = 2.3, 95% confidence interval [CI]: 1.7-3.1) and
      among those who smoked more than 20 cigarettes per day (OR = 1.7, 95% CI: 1.3
      2.2), compared with nonsmokers. Risk decreased with increasing NAT2 phenotypic
      activity (0: slow, 1: intermediate, and 2: rapid) (OR trend: 0.8; 95% CI: 0.7
      1.0, p-trend = 0.04) overall. When stratified by smoking status, significant
      phenotype-associated trends were observed among recent smokers (OR trend = 0.4,
      95% CI: 0.3-0.7, p trend <0.001) (p-interaction = 0.02), but not among past or
      nonsmokers. Diplotypes most strongly associated with lower risks in smokers were
      NAT2*4/*5B (OR = 0.3, 95% CI: 0.1-0.8, p = 0.01) and NAT2*4/*4 (OR = 0.2, 95% CI:
      0.04-0.7, p = 0.02), categorized as intermediate and rapid acetylators,
      respectively. One NAT1 diplotype, NAT1*4/*10 (OR = 0.5, 95% CI: 0.3-0.9, p =
      0.03), was also associated with a decreased risk in smokers. CONCLUSIONS: Our
      study indicated that NAT2 gene variants associated with a slow acetylator
      phenotype were more susceptible to the effects of tobacco smoking with respect to
      adenoma risk, providing leads for disease prevention.

PMID- 16981844
TI  - Systematic screening for polymorphisms in the CYP3A4 gene in the Chinese
      population.
AB  - OBJECTIVES: Cytochrome P450 3A4 (CYP3A4) is a major CYP enzyme in the liver and
      intestine. It is involved in the metabolism of over 50% of all drugs currently in
      use. The present study was designed to determine the genetic basis of CYP3A4
      variability. METHODS: Single nucleotide polymorphism (SNP) analysis of the CYP3A4
      gene was performed on 60 healthy Chinese subjects consisting of 20 Han, 30 She
      and ten Dong subjects, using direct sequencing. Linkage disequilibrium, haplotype
      inference and Hardy-Weinberg equilibrium were also determined for these samples.
      RESULTS: A total of 20 SNPs were found in the CYP3A4 gene, including 11 known
      SNPs and nine novel SNPs. The known SNPs detected in our study were CYP3A4*1B,
      CYP3A4*1G, CYP3A4*10, CYP3A4*13, CYP3A4*14, CYP3A4*15, CYP3A4*17, CYP3A4*18,
      rs3091339, rs3091430 and rs28371761, and the novel SNPs were -658 A-->C, G27A
      (E10K), T48A, G14284A (G167D), A15623G (N191D), C15635A (L196I), T15656C (F203L),
      G14199A (intron 5) and C15566T (intron 6). The allelic frequencies found in our
      sample varied from 1-37%. The novel SNPs detected in the CYP3A4 gene suggest that
      the Chinese population has different patterns of allele frequency compared with
      other populations. CONCLUSION: Several SNPs were detected in the CYP3A4 gene. The
      study of genetic variants in CYP3A4 may have an important significance for the
      understanding of genotype and phenotype relationships.

PMID- 16981845
TI  - Relationships between genetic polymorphisms and anticancer drug cytotoxicity vis
      a-vis the NCI-60 panel.
AB  - INTRODUCTION: The National Cancer Institute (NCI)-60 panel consists of 60 human
      tumor cell lines initially established for screening thousands of molecules for
      antiproliferative activity. It has been powerful for deciphering the
      relationships between anticancer drug cytotoxicity and cell molecular
      characteristics. We tested its potential interest for establishing relationships
      between the polymorphism of genes involved in drug metabolism and transport or in
      DNA repair, and drug cytotoxicity extracted from NCI databases. METHODS: Using
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      techniques, three frequent single nucleotide polymorphisms (SNPs) were analyzed:
      Lys751Gln in the Xeroderma pigmentosum complementation group D (XPD, ERCC2) gene,
      Asp1104His in the Xeroderma pigmentosum complementation group G (XPG, ERCC5) gene
      and Ile105Val in the glutathione S-transferase P1 (GSTP1) gene. RESULTS: The
      allelic frequencies of the variants were 33% for ERCC2, 23% for ERCC5 and 39% for
      GSTP1. The ERCC2 polymorphism appeared to be a strong determinant of the in vitro
      cytotoxicity of most anticancer agents, with lower half maximal inhibitory
      concentration (IC50) values in variant homozygous lines than in common homozygous
      or heterozygous cell lines. Unexpectedly, the cytotoxicity of taxanes appeared
      markedly dependent upon the ERCC2 genotype, with threefold lower mean IC50 values
      in variant homozygous cell lines. The ERCC5 genotype appeared to be important
      only for taxanes, with fourfold higher IC50 values in variant homozygous cell
      lines. The GSTP1 polymorphism was related to the cytotoxicity of several drug
      classes, especially topoisomerase inhibitors, antimetabolites and N7 alkylating
      agents. CONCLUSION: The NCI-60 panel is capable of providing clues and tracks for
      the establishment of clinically useful relationships between a given genotype and
      the cytotoxicity of an anticancer agent.

PMID- 16981846
TI  - A framework to evaluate the economic impact of pharmacogenomics.
AB  - INTRODUCTION: Pharmacogenomics and personalized medicine promise to improve
      healthcare by increasing drug efficacy and minimizing side effects. There may
      also be substantial savings realized by eliminating costs associated with failed
      treatment. This paper describes a framework using health claims data for
      analyzing the potential value of pharmacogenomic testing in clinical practice.
      METHODS: We evaluated a model of alternate clinical strategies using asthma
      patients' data from a retrospective health claims database to determine a
      potential cost offset. We estimated the likely cost impact of using a
      hypothetical pharmacogenomic test to determine a preferred initial therapy. We
      compared the annualized per patient costs distributions under two clinical
      strategies: testing all patients for a nonresponse genotype prior to treating and
      testing none. RESULTS: In the Test All strategy, more patients fall into lower
      cost ranges of the distribution. In our base case (15% phenotype prevalence, 200
      US dollars test, 74% overall first-line treatment efficacy and 60% second-line
      therapy efficacy) the cost savings per patient for a typical run of the testing
      strategy simulation ranged from 200 US dollars to 767 US dollars (5th and 95th
      percentile). Genetic variant prevalence, test cost and the cost of choosing the
      wrong treatment are key parameters in the economic viability of pharmacogenomics
      in clinical practice. CONCLUSIONS: A general tool for predicting the impact of
      pharmacogenomic-based diagnostic tests on healthcare costs in asthma patients
      suggests that upfront testing costs are likely offset by avoided nonresponse
      costs. We suggest that similar analyses for decision making could be undertaken
      using claims data in which a population can be stratified by response to a drug.

PMID- 16981847
TI  - Genetics of antipsychotic treatment emergent weight gain in schizophrenia.
AB  - Classic and modern antipsychotics can induce substantial weight gain causing
      diabetes, lipid abnormalities and psychological distress. Treatment emergent
      weight gain varies within the broad class of antipsychotics; however, an
      individual's propensity to develop weight gain largely depends on genetic
      factors. The first part of this review highlights current ideas and concepts
      related to antipsychotic-induced weight gain, including principles on energy
      homeostasis. The second part summarizes genetic findings emphasizing studies
      published after 2003 as prior studies have been reviewed in detail elsewhere.
      Candidate gene studies have produced significant findings in the 5
      hydroxytryptamin 2C (5HT2C) and adrenergic alpha2a (ADRalpha2a) receptor genes,
      as well as in the leptin, guanine nucleotide binding protein (GNB3) and
      synaptomal-associated protein 25kDa (SNAP25) genes. Results from genome-wide
      association and linkage studies point to several chromosomal regions (e.g.,
      12q24) and some specific genes (e.g., promelanin concentrating hormone [PMCH],
      polycyctic kidney and hepatic disease 1 [PKHD1], peptidylglycine alpha-amidating
      monooxygenase [PAM]). However, more efforts are needed before risk prediction and
      personalized medicine can be made available for antipsychotic-induced weight
      gain.

PMID- 16981848
TI  - Can pharmacogenetics help rescue drugs withdrawn from the market?
AB  - Observations over the later half of the last century have suggested that genetic
      factors may be the prime determinant of drug response, at least for some drugs.
      Retrospectively gathered data have provided further support to the notion that
      genotype-based prescribing will improve the overall efficacy rates and minimize
      adverse drug reactions (ADRs), making personalized medicine a reality. During the
      last 16 years, 38 drugs have been withdrawn from major markets due to safety
      concerns. Inevitably, a question arises as to whether it might be possible to
      'rescue' some of these drugs by promoting genotype-based prescribing. However,
      ironically pharmacogenetics has not perceptibly improved the risk/benefit of a
      large number of genetically susceptible drugs that are already in wide clinical
      use and are associated with serious ADRs. Drug-induced hepatotoxicity and QT
      interval prolongation (with or without torsade de pointes) account for 24 (63%)
      of these 38 drug withdrawals. In terms of the number of drugs implicated, both
      these toxicities are on the increase. Many others have had to be withdrawn due to
      their inappropriate use. This paper discusses the criteria that a drug would need
      to fulfill, and summarizes the likely regulatory requirements, before its
      pharmacogenetic rescue can be considered to be realistic. One drug that fulfils
      these criteria is perhexiline (withdrawn worldwide in 1988) and is discussed in
      some detail. For the majority of these 38 drugs there are, at present, no
      candidates for genetic traits to which the toxicity that led to their withdrawal
      may be linked. For a few other drugs where a potential candidate for a genetic
      trait might explain the toxicity of concern, the majority of patients who
      experienced the index toxicity had easily managed nongenetic risk factors. It may
      be possible to rescue these drugs simply by careful attention to their dose,
      interaction potential and prescribing patterns, but without the need for any
      pharmacogenetic test. In addition, the pharmacogenetic rescue of drugs might not
      be as effective as anticipated as hardly any pharmacogenetic test is known to
      have the required test efficiency to promote individualized therapy. Multiple
      pathways of drug elimination, contribution to toxicity by metabolites as well as
      the parent drug, gene-gene interactions, multiple mechanisms of toxicity and
      inadequate characterization of phenotype account for this lack of highly
      predictive tests. The clinical use of tests that lack the required efficiency
      carries the risks of over- or under-dosing some patients, denying the drug to
      others and decreasing physician vigilance of patients. Above all, at present,
      prescribing physicians lack an adequate understanding of pharmacogenetics and its
      limitations. It is also questionable whether their prescribing will comply with
      the requirements for pretreatment pharmacogenetic tests to make pharmacogenetic
      rescue a realistic goal.

PMID- 16981849
TI  - The genomics of new drugs in sickle cell disease.
AB  - The quality of life of patients with sickle cell disease in developed countries
      has improved significantly over the past two decades. Currently available
      measures to prevent the painful crises and the complications of the disease
      include the use of penicillin prophylaxis, antipneumonococcal vaccine, folate
      administration, chronic red cell transfusions in patients with cerebrovascular
      disease, iron chelating agents, fetal hemoglobin-enhancing agents, such as
      hydroxyurea, decitabine and butyrate, drugs that augment the endogenous nitric
      oxide levels and agents that restore red cell dehydration. Sickle cell patients
      show a broad phenotypic expression and a great variability in treatment response.
      Genetic association studies, which attempt to link polymorphisms with certain
      disease phenotypes and drug response, are taking the first steps in aiding
      individualized therapy in sickle cell patients in order to enhance efficacy and
      reduce toxicity.

PMID- 16981850
TI  - Pharmacogenomics of beta2-agonist: key focus on signaling pathways.
AB  - Asthma is one of the most common respiratory diseases, where inhalation and
      exhalation are obstructed due to narrowing of the airways by broncho-constriction
      or by inflammation. Among all the available anti-asthma therapies, beta2-agonists
      are the most effective bronchodilators available, and give rapid relief of asthma
      symptoms. Evidence suggests that the degree of beta2-agonist response varies
      greatly between patients and genetic factors have a major role in it. Despite
      several studies on the beta2-agonist pharmacogenetics, significant gaps in
      knowledge still remain and need to be resolved before the pharmacotyping of beta2
      agonist responsiveness comes to clinical practice. As we know, beta2-agonists
      show their influence by targeting beta2-adrenergic receptors, leading to the
      activation of beta2-adrenergic receptors and its downstream cascade. Signaling
      through beta2-adrenergic receptors mediates numerous airway functions by
      regulating broncho-constriction and dilation pathways. Therefore, it is an
      important prerequisite to understand these pathways, which will assist in
      defining the variability in therapeutic responses for beta2-agonists. Owing to
      the complexity of the action of a beta2-agonist and its therapeutic response, a
      broader genomics approach will help in optimizing therapy for the individual
      patient. This might be achieved by considering and focusing on receptor/s at
      which the drug binds directly, signal transduction cascades or downstream
      proteins and proteins involved in the relaxation and constriction of the airway
      smooth muscle. Considering that a drug response may involve a large number of
      proteins, it seems unlikely that a single polymorphism or haplotype in a single
      gene would explain a high degree of drug response variability in a consistent
      fashion. Thus, it shows that a polygenic approach will be more appropriate. In
      order to follow this, the mode of action of the beta2-agonist and its downstream
      signaling cascade should essentially be assessed to resolve the beta2-agonist
      enigma.

PMID- 16981851
TI  - A review of the ethnic differences in breast cancer.
AB  - Women of African descent have a lower incidence of breast cancer than their white
      counterparts; however, the overall age-adjusted breast cancer mortality rates are
      higher. They also present at a younger age, and have more advanced disease that
      exhibits poor prognostic features including significantly larger tumors of higher
      grade, higher rates of estrogen receptor and progesterone receptor negativity and
      a higher rate of p53 mutations and HRAS1 proto-oncogene expression, all of which
      confer a poor prognosis. While there are many possible contributory factors to
      the discrepancies in outcome in women of African descent, there is no
      satisfactory explanation as to why women of African origin tend to present at a
      younger age with hormone receptor-negative tumors and more adverse prognostic
      features.

PMID- 16981852
TI  - Translational medicine: the discovery of bridging biomarkers using
      pharmacogenomics.

PMID- 16981853
TI  - Ribose 5-phosphate isomerase type B from Trypanosoma cruzi: kinetic properties
      and site-directed mutagenesis reveal information about the reaction mechanism.
AB  - Trypanosoma cruzi, the human parasite that causes Chagas disease, contains a
      functional pentose phosphate pathway, probably essential for protection against
      oxidative stress and also for R5P (ribose 5-phosphate) production for nucleotide
      synthesis. The haploid genome of the CL Brener clone of the parasite contains one
      gene coding for a Type B Rpi (ribose 5-phosphate isomerase), but genes encoding
      Type A Rpis, most frequent in eukaryotes, seem to be absent. The RpiB enzyme was
      expressed in Escherichia coli as a poly-His tagged active dimeric protein, which
      catalyses the reversible isomerization of R5P to Ru5P (ribulose 5-phosphate) with
      Km values of 4 mM (R5P) and 1.4 mM (Ru5P). 4-phospho-D-erythronohydroxamic acid,
      an analogue to the reaction intermediate when the Rpi acts via a mechanism
      involving the formation of a 1,2-cis-enediol, inhibited the enzyme competitively,
      with an IC50 value of 0.7 mM and a Ki of 1.2 mM. Site-directed mutagenesis
      allowed the demonstration of a role for His102, but not for His138, in the
      opening of the ribose furanosic ring. A major role in catalysis was confirmed for
      Cys69, since the C69A mutant was inactive in both forward and reverse directions
      of the reaction. The present paper contributes to the know-ledge of the mechanism
      of the Rpi reaction; in addition, the absence of RpiBs in the genomes of higher
      animals makes this enzyme a possible target for chemotherapy of Chagas disease.

PMID- 16981854
TI  - MEGF9: a novel transmembrane protein with a strong and developmentally regulated
      expression in the nervous system.
AB  - MEGF9 [multiple EGF (epidermal growth factor)-like-domains 9], a novel
      transmembrane protein with multiple EGF-like repeats, is predominantly expressed
      in the developing and adult CNS (central nervous system) and PNS (peripheral
      nervous system). The domain structure of MEGF9 consists of an N-terminal region
      with several potential O-glycosylation sites followed by five EGF-like domains,
      which are highly homologous with the short arms of laminins. Following one single
      pass transmembrane domain, a highly conserved short intracellular domain with
      potential phosphorylation sites is present. The protein was recombinantly
      expressed and characterized as a tissue component. To study the expression
      pattern further, immunohistochemistry was performed and staining was detected in
      Purkinje cells of the cerebellum and in glial cells of the PNS. Additional
      expression was observed in the epidermal layer of skin, papillae of the tongue
      and the epithelium of the gastrointestinal tract. By immunoelectron microscopy,
      MEGF9 was detected in glial cells of the sciatic nerve facing the basement
      membrane. MEGF9 represents a novel putative receptor, expressed in neuronal and
      non-neuronal tissues, that is regulated during development and could function as
      a guidance or signalling molecule.

PMID- 16981855
TI  - Precise mapping of an IGF-I-binding site on the IGF-1R.
AB  - The IGF-1R [type 1 IGF (insulin-like growth factor) receptor] is activated upon
      binding to IGF-I and IGF-II leading to cell growth, survival and migration of
      both normal and cancerous cells. We have characterized the binding interaction
      between the IGF-1R and its ligands using two high-affinity mouse anti-IGF-1R mAbs
      (monoclonal antibodies), 7C2 and 9E11. These mAbs both block IGF-I binding to the
      IGF-1R but have no effect on IGF-II binding. Epitope mapping using chimaeras of
      the IGF-1R and insulin receptor revealed that the mAbs bind to the CR (cysteine
      rich) domain of IGF-1R. The epitope was finely mapped using single point
      mutations in the IGF-1R. Mutation of Phe241, Phe251 or Phe266 completely
      abolished 7C2 and 9E11 binding. The three-dimensional structure showed that these
      residues cluster on the surface of the CR-domain. BIAcore analyses revealed that
      IGF-I and a chimaeric IGF-II with the IGF-I C-domain competed for the binding of
      both mAbs with the IGF-1R, whereas neither IGF-II nor a chimaeric IGF-I with the
      IGF-II C-domain affected antibody binding. We therefore conclude the IGF-I C
      domain interacts with the CR (cysteine-rich) domain of the receptor at the
      cluster of residues Phe241, Phe251 and Phe266. These results allow precise
      orientation of IGF-I within the IGF-I-IGF-1R complex involving the IGF-I C-domain
      binding to the IGF-1R CR domain. In addition, mAbs 7C2 and 9E11 inhibited both
      IGF-I- and IGF-II-induced cancer cell proliferation, migration and IGF-1R down
      regulation, demonstrating that targeting the IGF-1R is an effective strategy for
      inhibition of cancer cell growth.

PMID- 16981856
TI  - Contraception for women with epilepsy.
AB  - Antiepileptic drugs that induce hepatic enzyme activity may alter the metabolism
      of most hormonal methods of contraception, and this affects the contraceptive
      regime. This effect should be considered in the choice of both the treatment of
      the epilepsy and the choice of contraceptive method. This review considers these
      interactions and offers advice about their management.

PMID- 16981858
TI  - Effects of carbamazepine and oxcarbazepine on the reproductive endocrine function
      in women with epilepsy.
AB  - PURPOSE: The aim of the study was to compare the effects of carbamazepine (CBZ)
      and oxcarbazepine (OXC) on the reproductive endocrine function in women with
      epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of
      reproductive dysfunction in women treated with OXC monotherapy for epilepsy has
      not been studied previously. METHODS: Thirty-five women with epilepsy were
      examined in the Department of Neurology at Oulu University Hospital. Sixteen
      patients were treated with CBZ monotherapy, and nineteen patients were treated
      with OXC monotherapy. The subjects were clinically examined, vaginal
      ultrasonography was performed, and serum sex hormone concentrations were
      measured. RESULTS: The women taking CBZ or OXC had lower serum testosterone (T)
      levels and lower free androgen indexes (FAIs) than the control subjects. CBZ
      medication was associated with increased concentrations of serum sex hormone
      binding globulin (SHBG). The patients taking OXC had higher concentrations of
      dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women
      taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the
      OXC-treated women. CONCLUSIONS: CBZ and OXC have different effects on the
      reproductive endocrine function. Although both drugs were associated with low
      serum T concentrations and low FAIs, only OXC was associated with a high
      frequency of elevated levels of A and DHEAS and with an increased prevalence of
      PCOs. These findings suggest that OXC may be disadvantageous for women with
      epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.

PMID- 16981859
TI  - Hormone replacement therapy in women with epilepsy: a randomized, double-blind,
      placebo-controlled study.
AB  - PURPOSE: Previous reports have suggested that hormone replacement therapy (HRT)
      could increase seizure activity in women with epilepsy. We sought to determine
      whether adding HRT to the medication regimen of postmenopausal women with
      epilepsy was associated with an increase in seizure frequency. METHODS: This was
      a randomized, double-blind, placebo-controlled trial of the effect of HRT on
      seizure frequency in postmenopausal women with epilepsy, taking stable doses of
      antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3
      month prospective baseline, subjects were randomized to placebo, Prempro (0.625
      mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or
      CEE/MPA) daily, or double-dose CEE/MPA daily for a 3-month treatment period.
      RESULTS: Twenty-one subjects were randomized after completing baseline. The
      subjects' ages ranged from 45 to 62 years (mean, 53 years; SD, +/-5), and the
      number of AEDs used ranged from none to three (median, one). Five (71%) of seven
      subjects taking double-dose CEE/MPA had a worsening seizure frequency of at least
      one seizure type, compared with four (50%) of eight taking single-dose CEE/MPA
      and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency
      of the subject's most severe seizure type was associated with increasing CEE/MPA
      dose (p = 0.008). An increase in complex partial seizure frequency also was
      associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking
      lamotrigine had a decrease in lamotrigine levels of 25-30% while taking CEE/MPA.
      CONCLUSIONS: CEE/MPA is associated with a dose-related increase in seizure
      frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine
      levels.

PMID- 16981860
TI  - Interictal and postictal circadian and ultradian luteinizing hormone secretion in
      men with temporal lobe epilepsy.
AB  - PURPOSE: Hypothalamic regulation of the reproductive axis in temporal lobe
      epilepsy (TLE), represented by the ultradian pulsatile secretion of luteinizing
      hormone (LH), has been shown to be altered interictally and postictally. Our
      objective is to determine if epilepsy or seizures disrupt normal circadian
      fluctuations of LH as well as circadian organization of ultradian bursts of LH.
      METHODS: We characterized LH secretion in 10 men with TLE during two 24-h blocks:
      an interictal epoch and a postictal epoch initiated by a seizure. Serum LH was
      measured every 10 min and characterized by circadian and ultradian patterns with
      cosinor and deconvolution analysis. RESULTS: Mean peak serum concentrations of LH
      occurred at approximately 0400 in controls, were significantly delayed
      approximately 5 h interictally, and were randomly distributed postictally. Burst
      amplitudes differed significantly by phase among controls, with the largest
      amplitudes between 0101 and 0700 and the smallest between 1301 and 1900. No phase
      differences were present in interictal or postictal epochs. Burst frequency
      weakly but significantly was slowest between 0101 and 0700 in controls, but did
      not differ significantly by phase in either interictal or postictal epochs.
      Postictal LH burst frequencies, but not amplitudes, were significantly decreased
      immediately postictally. CONCLUSION: The pulsatile secretion of LH in TLE is
      abnormal both in the circadian as well as the ultradian domain. Interictal
      effects consist mainly in loss of circadian fluctuations in LH burst amplitude,
      whereas postictal effects consist of altered burst timing. Altered daily patterns
      of neuroendocrine signals may underlie other disorders of homeostasis in TLE.

PMID- 16981857
TI  - The influence of gonadal hormones on neuronal excitability, seizures, and
      epilepsy in the female.
AB  - It is clear from both clinical observations of women, and research in laboratory
      animals, that gonadal hormones exert a profound influence on neuronal
      excitability, seizures, and epilepsy. These studies have led to a focus on two of
      the primary ovarian steroid hormones, estrogen and progesterone, to clarify how
      gonadal hormones influence seizures in women with epilepsy. The prevailing view
      is that estrogen is proconvulsant, whereas progesterone is anticonvulsant.
      However, estrogen and progesterone may not be the only reproductive hormones to
      consider in evaluating excitability, seizures, or epilepsy in the female. It
      seems unlikely that estrogen and progesterone would exert single, uniform actions
      given our current understanding of their complex pharmacological and
      physiological relationships. Their modulatory effects are likely to depend on
      endocrine state, relative concentration, metabolism, and many other factors.
      Despite the challenges these issues raise to future research, some recent
      advances have helped clarify past confusion in the literature. In addition,
      testable hypotheses have developed for complex clinical problems such as
      "catamenial epilepsy." Clinical and animal research, designed with the relevant
      endocrinological and neurobiological issues in mind, will help advance this field
      in the future.

PMID- 16981861
TI  - Characterization of insulin secretion in Valproate-treated patients with
      epilepsy.
AB  - PURPOSE: Valproate (VPA) treatment has been reported to be associated with
      obesity and high fasting serum insulin concentrations in parallel with an
      unfavorable serum lipid profile and hyperandrogenism and polycystic ovaries in
      women. The pathogenetic mechanism underlying these changes has remained unknown,
      although several mechanisms have been implicated. METHODS: Fifty-one patients
      receiving monotherapy (31 male and 20 female patients) were included in this
      study, with 45 (23 male and 22 female) healthy control subjects. These
      participants were interviewed, clinically examined, and blood samples for fasting
      plasma glucose, serum insulin, proinsulin, and C-peptide concentrations were
      taken after an overnight fast. RESULTS: The valproate-treated patients had
      fasting hyperinsulinemia (11.30 +/- 6.23 pM vs. 6.28 +/- 4.66 pM in the control
      subjects; p < 0.001), although the fasting serum proinsulin and C-peptide
      concentrations were not significantly higher in the patients than in the control
      subjects. In addition, proinsulin/insulin (0.30 +/- 0.14) and C-peptide/insulin
      ratios (35.48 +/- 24.09) were lower (p < 0.001) in the VPA-treated patients when
      compared with the control subjects (0.53 +/- 0.36 and 94.27 +/- 61.85,
      respectively), and they also had lower fasting plasma glucose concentrations
      (4.72 +/- 0.35 mM) than the control subjects (5.12 +/- 0.58 mM; p < 0.01).
      CONCLUSIONS: This study suggests that valproate does not induce insulin secretion
      but might interfere with the insulin metabolism in the liver, resulting in higher
      insulin concentrations in the peripheral circulation. These changes are seen
      irrespective of concomitant weight gain, suggesting that increased insulin
      concentrations induce weight gain and not vice versa.

PMID- 16981863
TI  - Electrocorticographic discharge patterns in glioneuronal tumors and focal
      cortical dysplasia.
AB  - PURPOSE: To determine whether highly epileptiform electrocorticographical
      discharge patterns occur in patients with glioneuronal tumors (GNTs) and focal
      cortical dysplasia (FCD) and whether specific histopathological features are
      related to such patterns. METHODS: The series consists of operated patients with
      pharmacoresistant epilepsy because of FCD or GNT between 1992 and 2003.
      Electrocorticography was reviewed for presence of continuous spiking, bursts,
      recruiting discharges, or sporadic spikes. Surgical specimens were reviewed for
      the presence of balloon cells, (coexisting) cortical dysplasia, and relative
      frequencies of neurons, glia, and microglia. RESULTS: Continuous spiking was seen
      in 55% versus 12% of patients with FCD and GNT, respectively (p = 0.005). Bursts
      and recruiting discharges were seen in a similar proportion of patients with FCD
      or GNT. Ninety-one percent of patients with continuous spiking showed
      (coexisting) cortical dysplasia in contrast to 42% of patients without this
      pattern (p = 0.004). The presence of balloon cells and glia or microglia content
      were not associated with discharge patterns. CONCLUSION: Continuous spiking,
      bursts, and recruiting discharges occur in patients with FCD and GNT. Continuous
      spiking was seen significantly more often in patients with FCD. When continuous
      spiking is found with GNT, it is likely to be associated with dysplastic regions
      with a high neuronal density.

PMID- 16981862
TI  - High-frequency intracerebral EEG activity (100-500 Hz) following interictal
      spikes.
AB  - PURPOSE: High-frequency activity has been recorded with intracerebral
      microelectrodes in epileptic patients and related to seizure genesis. Our goal
      was to analyze high-frequency activity recorded with electroencephalograph (EEG)
      macroelectrodes during the slow wave immediately following interictal spikes,
      given the potential importance of this presumed hyperpolarization in transforming
      spikes into seizures. METHODS: Depth electrode EEG recordings from 10 patients
      with intractable focal epilepsy were low-pass filtered at 500 Hz and sampled at
      2,000 Hz. Spikes were categorized according to localization and morphology.
      Segments of 256 ms were selected immediately following (postspike), and 2 s
      before each spike (baseline). Power was estimated in subgamma (0-40 Hz), gamma
      (40-100 Hz), high frequency (100-200 Hz), and very high frequency (250-500 Hz)
      bands. RESULTS: Changes in power above 100 Hz were seen in 22 of 29 spike
      categories, consisting primarily of a widespread decrease in frequencies above
      100 Hz. This decrease became spatially more restricted as frequencies increased,
      and coincided with the localization of largest spikes for the highest
      frequencies. High-frequency power decreases were prominent in the hippocampus but
      less common in amygdala and neocortex. High-frequency power increases were
      observed in the amygdala. CONCLUSIONS: Thus high-frequency EEG activity can be
      recorded with macroelectrodes in humans and may provide insights on neuronal
      mechanisms related to human epilepsy. This activity undergoes consistent
      modifications after EEG spikes. We propose that the reduction in high frequencies
      reflects a postspike depression in neuronal activity that is more pronounced in
      the region of spike generation. This depression is almost always seen in
      hippocampus but less in amygdala.

PMID- 16981864
TI  - Event-related fMRI of myoclonic jerks arising from dysplastic cortex.
AB  - BACKGROUND: Malformations of cortical development can cause epileptiform activity
      and myoclonic jerks, yet EEG correlates of jerks can be difficult to obtain.
      METHODS: We studied a woman who had frequent episodes of persistent right-foot
      jerking since childhood. Ictal and interictal EEG had shown no localizing
      epileptiform activity. Functional imaging experiments were performed with
      concurrent video monitoring to document the timing of foot jerks. These studies
      mapped brain regions controlling voluntary right- and left-foot movements, and
      spontaneous right-foot jerks. RESULTS: High-resolution structural MR imaging
      revealed a dysplastic gyrus extending anteriorly off the left central sulcus.
      Event-related analysis of spontaneous jerks revealed prominent activation of the
      left precentral gyrus (right-foot motor area), bilateral medial frontal regions
      (supplementary motor area), and the dysplastic gyrus. Hemodynamic response
      modeling to foot jerks revealed the hemodynamic response peaked earlier in the
      dysplastic cortex and SMA regions than in the foot area. DISCUSSION: Event
      related fMRI in a patient with spontaneous and induced epileptic foot jerks
      revealed brain regions active during jerks. The results of this analysis allowed
      us to tailor subsequent intracerebral recordings. Analysis of the timing of the
      hemodynamic response showed certain brain regions with an earlier rise in BOLD
      signal, suggesting a possible initiating role, or different hemodynamic response
      functions. Hemodynamic response timing should be considered carefully when
      interpreting event-related studies of epileptiform activity.

PMID- 16981865
TI  - Prolonged febrile seizures are associated with hippocampal vasogenic edema and
      developmental changes.
AB  - PURPOSE: There is mounting evidence that a prolonged febrile seizure (PFS) can
      cause acute hippocampal edema although the nature of that edema remains
      uncertain. The principal aims of the current study were: (1) to use apparent
      diffusion coefficient (ADC) measurements to further characterize the hippocampal
      edema previously identified within 5 days of a PFS, and (2) to determine whether
      the age dependency of ADC in the hippocampus is different in patients when
      compared to a control population following a PFS. METHODS: Diffusion weighted
      imaging was acquired in 23 children within 5 days of a PFS, and in 14 of these
      children a mean of 5.5 months later. Twenty-four control children were enrolled.
      RESULTS: There was a reduction in ADC between the acute and follow-up
      investigations [mean reduction = 0.0072 mm2/s/month since PFS (95% confidence
      interval; 0.0001-0.014 mm2/s/month since PFS), p = 0.048] consistent with early
      vasogenic edema, followed by recovery in children investigated within 2 days of a
      PFS. In addition, the behavior of ADC with respect to age was different in
      patients when compared to control subjects [mean difference in slope =-0.155
      mm2/s/log10 age (95% confidence interval; -0.290-0.0203 mm2/s/log10 age), p =
      0.029], in that the expected age dependence was observed only in the control
      subjects. CONCLUSION: We suggest that these latter findings are most consistent
      with a preexisting developmental hippocampal abnormality that may predispose
      individuals to having a PFS.

PMID- 16981866
TI  - How long do most seizures last? A systematic comparison of seizures recorded in
      the epilepsy monitoring unit.
AB  - PURPOSE: More information is needed regarding how long seizures typically last,
      since this influences treatment decisions. Seizure type and other factors could
      influence seizure duration. METHODS: Data were collected from a random sample of
      patients being evaluated with continuous video and scalp EEG. Seizure duration
      was defined as time from early sign of seizure (clinical or EEG) until the end of
      seizure on EEG. Seizures were categorized as simple partial (SPS), complex
      partial (CPS), secondarily generalized tonic-clonic (SGTCS), primary generalized
      tonic-clonic (PGTCS) and tonic (TS). SGTCS were divided into a complex partial
      part (SGTCS/CP) and a tonic-clonic part (SGTCS/TC). Median and longest duration
      of each seizure type in each individual were used. Comparisons of seizure types,
      first and last seizure, area of onset, and state of onset were performed.
      RESULTS: Five hundred seventy-nine seizures were recorded in 159 adult patients.
      Seizures with partial onset spreading to both hemispheres had the longest
      duration. SGTCS were unlikely to last more than 660 s, CPS more than 600 s, and
      SPS more than 240 s. PGTCS and TS had shorter durations, but the number of
      subjects with those two types was small. CPS did not differ in duration according
      to sleep state at onset nor side of origin. CONCLUSION: A working definition of
      status epilepticus in adults with cryptogenic or symptomatic epilepsy can be
      drawn from these data for purposes of future epidemiologic research. More
      information is needed for the idiopathic epilepsies and in children.

PMID- 16981867
TI  - Nonconvulsive status epilepticus in children: clinical and EEG characteristics.
AB  - BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a highly heterogeneous
      clinical condition that is understudied in the pediatric population. OBJECTIVE:
      To analyze the epidemiological, clinical, and electroencephalograpic features in
      pediatric patients with NCSE. METHODS: We identified 19 pediatric patients with
      NCSE from the epilepsy database of the Comprehensive Epilepsy Center at, Columbia
      University between June 2000 and December 2003. Continuous
      electroencephalographic (EEG) monitoring was analyzed and chart review was
      performed. RESULTS: The patients ranged from 1 month old to 17 years of age. Five
      patients developed NCSE following convulsive status epilepticus (CSE), and a
      further 12 patients developed NCSE after brief convulsions. Two developed NCSE as
      the first manifestation during a comatose state following hypoxic events. Acute
      hypoxic-ischemic injury was the most frequent etiology of NCSE in our population
      (5 of 19; 26%), followed by exacerbation of underlying neurometabolic disease (4
      of 19; 21%), acute infection (3 of 19; 16%), change in antiepileptic drug regimen
      (3 of 19;16%), refractory epilepsy (2 of 19; 11%) and intracranial hemorrhage (2
      of 19; 11%). Six patients had associated periodic lateralized epileptiform
      discharges (PLEDs), one had generalized periodic epileptiform discharges (GPEDs).
      Five (5 of 19; 26%) patients died of the underlying acute medical illness.
      Periodic discharges were associated with worse outcome. CONCLUSION: The majority
      of our patients with NCSE had preceding seizures in the acute setting prior to
      the diagnosis of NCSE, though most of these seizures were brief, isolated
      convulsions (12 patients) rather than CSE (five patients). Prolonged EEG
      monitoring to exclude NCSE may be warranted in pediatric patients even after
      brief convulsive seizures. Prompt recognition and treatment may be necessary to
      improve neurological outcome.

PMID- 16981868
TI  - Nonconvulsive seizures in the pediatric intensive care unit: etiology, EEG, and
      brain imaging findings.
AB  - PURPOSES: To determine the occurrence of nonconvulsive seizures (NCS) in the
      Pediatric Intensive Care Unit (PICU); to ascertain the relationship of NCS to
      past medical history, etiology, EEG, and brain imaging; and to determine the
      concordance between abnormal EEG findings and neuroimaging abnormalities.
      METHODS: A retrospective review was conducted of all pediatric patients who were
      admitted or transferred to the PICU from January 2000 to December 2003 with an
      unexplained decrease in level of consciousness, no overt clinical seizures, and
      EEG recordings performed within the 24 h of onset of an altered state of
      consciousness. RESULTS: Twenty-three of 141 patients who met criteria for
      inclusion in the study (16.3%) were found to have NCS. The male to female ratio
      was 1.9:1. The largest group of patients (43%) had no preexisting neurological
      condition prior to the onset of NCS. In the remainder, the etiology of NCS
      included: acute structural brain lesion (48%), acute nonstructural brain lesion
      (22%), epilepsy-related seizure (13%), and others (17%). Epileptic foci were
      lateralized to the right side in 39.2%, the left side in 30.4%, and were
      bilateral in 30.4%. Of 23 patients with NCS, 18 (78.3%) demonstrated abnormal
      neuroimaging. In 10 of 18 of these patients (55.6%), the findings on neuroimaging
      were concordant with the lateralization found on EEG (p < 0.05, Fisher's exact
      test). CONCLUSIONS: NCS are not uncommon in pediatric patients with an altered
      state of consciousness. Almost half of the patients were previously healthy
      especially if they were under 6 months of age. This report highlights the
      importance of clinical awareness of NCS in the PICU.

PMID- 16981869
TI  - Substantia nigra is an anticonvulsant site of action of topiramate in the focal
      pilocarpine model of limbic seizures.
AB  - PURPOSE: The substantia nigra pars reticulata (SNR) is known to play a role in
      gating and control of seizures. Prompted by the observation that intrahippocampal
      topiramate (TPM) administration does not suppress limbic seizures in the focal
      pilocarpine model, we investigated the role of the SNR in the anticonvulsant
      mechanism of action of TPM. METHODS: Limbic seizures were evoked in freely moving
      rats by intrahippocampal administration of pilocarpine via a microdialysis probe.
      Changes in hippocampal extracellular (EC) glutamate and GABA concentrations were
      monitored. Effects of intraperitoneal (10-200 mg/kg), intrahippocampal (1-5 mM),
      and bilateral intranigral (100-300 nmol) TPM administration on pilocarpine
      induced seizures and neurochemical changes were evaluated. Effects of TPM
      administration alone on hippocampal and nigral EC amino acid concentrations were
      also studied. RESULTS: Systemic and intranigral, but not intrahippocampal TPM
      administration suppressed pilocarpine-induced seizures and neurochemical changes.
      Nigral GABA(A) receptor blockade by picrotoxin abolished the anticonvulsant
      effect of TPM in SNR. Systemic TPM administration increased hippocampal glutamate
      and decreased GABA. Intranigral TPM administration increased hippocampal
      glutamate, but not GABA. Intrahippocampal TPM increased hippocampal glutamate and
      GABA, but only at high concentrations. CONCLUSIONS: In the focal pilocarpine
      model, TPM does not exert its anticonvulsant effect at the site of seizure
      initiation. We identified the SNR as a site of action of TPM, and showed that the
      nigral GABA-ergic system is central to TPM's anticonvulsant effect in SNR.
      Anticonvulsant effects and neurochemical changes in hippocampus following
      intranigral TPM administration suggest the existence of a nigro-hippocampal
      circuit, which may be involved in the control of limbic seizures.

PMID- 16981870
TI  - The BOLD effect of interictal spike activity in childhood occipital lobe
      epilepsy.
AB  - PURPOSE: Occipital lobe epilepsy (OLE) presents in childhood with different
      manifestations, age of onset and EEG features that form distinct syndromes. The
      ictal clinical symptoms are difficult to correlate with onset in particular areas
      in the occipital lobes, and the EEG recordings have not been able to overcome
      this limitation. The mapping of epileptogenic cortical regions in OLE remains
      therefore an important goal in our understanding of these syndromes. METHODS: In
      this work, three patients with two types of idiopathic childhood OLE were studied
      with EEG source analysis and also with mapping of the BOLD effect associated with
      spikes in simultaneous EEG/fMRI recordings. RESULTS: Two patients with late onset
      OLE provided EEG source localizations in the lateral parietal cortex and in the
      medial occipital areas. The BOLD activations were more consistent and restricted
      to the medial parietal-occipital cortex in both cases. One patient with
      photosensitive idiopathic OLE presented with dipole sources in the medial
      parietal cortex, but the BOLD activations were widespread over inferior and
      bilateral occipital areas and also posterior temporal ones. There was little
      spatial overlap between the EEG and BOLD results, but the localizations suggested
      by the latter are more consistent with the ictal clinical manifestations of each
      type of epileptic syndrome. CONCLUSIONS: Overall, the BOLD effect associated with
      interictal spikes maps epileptogenic areas to different localizations than the
      ones suggested by EEG source analysis. These maps are similar in two patients
      with late onset idiopathic OLE, but different from a case of photosensitive
      idiopathic OLE.

PMID- 16981871
TI  - FDG-PET/MRI coregistration and diffusion-tensor imaging distinguish epileptogenic
      tubers and cortex in patients with tuberous sclerosis complex: a preliminary
      report.
AB  - PURPOSE: Patients with tuberous sclerosis complex (TSC) are potential surgical
      candidates if the epileptogenic region(s) can be accurately identified. This
      retrospective study determined whether FDG-PET/MRI coregistration and diffusion
      tensor imaging (DTI) showed better accuracy in the localization of epileptogenic
      cortex than structural MRI in TSC patients. METHODS: FDG-PET/MRI coregistration
      and/or DTI for apparent diffusion coefficient (ADC) and fractional anisotropy
      (FA) were utilized in 15 TSC patients. Presurgery scalp EEG and postsurgery
      seizure control identified epileptogenic tubers (n = 27) and these were compared
      with nonepileptogenic tubers (n = 204) for MRI tuber volume, volume of FDG-PET
      hypometabolism on MRI coregistration, DTI, ADC, and FA values. RESULTS: Compared
      with nonepileptogenic tubers, epileptogenic regions had increased volume of FDG
      PET hypometabolism (p < 0.0001), and increased ADC values in subtuber white
      matter (p < 0.0001). In contrast, the largest MRI identified tuber (p = 0.046)
      and decreased FA values (p = 0.58) were less accurate in identifying
      epileptogenic regions. Larger volumes of FDG-PET hypometabolism correlated
      positively with increased ADC values (p = 0.029), and localized to areas of
      cortical dysplasia adjacent to the tuber in four cases. CONCLUSIONS: Larger
      volumes of FDG-PET hypometabolism relative to MRI tuber size and higher ADC
      values identified epileptogenic tubers and adjoining cortex containing cortical
      dysplasia in TSC patients with improved accuracy compared with largest tuber by
      MRI or lowest FA values. Used in conjunction with ictal scalp EEG and interictal
      magnetoencephalography, these newer neuroimaging techniques should improve the
      noninvasive evaluation of TSC patients with intractable epilepsy in
      distinguishing epileptogenic sites for surgical resection.

PMID- 16981872
TI  - Ictal perfusion patterns associated with single MRI-visible focal dysplastic
      lesions: implications for the noninvasive delineation of the epileptogenic zone.
AB  - BACKGROUND: Invasive electroencephalogram (EEG) studies are often considered
      necessary to localize the epileptogenic zone in partial epilepsies associated
      with focal dysplastic lesions (FDL). Our aim was to evaluate the relationships
      between subtraction ictal SPECT coregistered with magnetic resonance imaging
      (MRI) (SISCOM) hyperperfusion clusters and MRI-visible FDL, and to establish a
      preliminary algorithm for a noninvasive presurgical evaluation protocol for MRI
      visible FDLs in patients with refractory epilepsy. METHODS: Fifteen consecutive
      patients with refractory partial epilepsy and a single MRI-visible FDL underwent
      a noninvasive presurgical evaluation including SISCOM. Each hyperperfusion
      cluster was visually analyzed, automatically quantitated, and its distance form
      the lesion as outlined on the MRI was measured. In patients who underwent
      surgery, the volumes of resected brain tissue containing the FDL, the SISCOM
      hyperperfusion cluster, and surrounding regions were assessed on postoperative
      MRI and correlated with surgical outcome. RESULTS: Fourteen of the 15 patients
      (93%) showed SISCOM hyperperfusion overlapping with the FDL. The FDL was detected
      only after reevaluation of the MRI guided by the ictal SPECT in 7 of the 15
      patients (47%). Four distinct hyperperfusion patterns were observed, representing
      different degrees of seizure propagation. Nine patients have been operated on.
      Five have been seizure-free since surgery and one since a reoperation. The degree
      of resection of the MRI-visible FDL was the major determinant of surgical
      outcome. Full resection of the SISCOM hyperperfusion cluster was not required to
      render a patient seizure-free. CONCLUSION: Detailed analysis of SISCOM
      hyperperfusion patterns is a promising tool to detect subtle FDL on MRI and to
      establish the epileptic nature of these lesions noninvasively. Overlap between
      the SISCOM hyperperfusion cluster and MRI-visible FDL in a noninvasive
      presurgical evaluation with concordant data may suffice to proceed to epilepsy
      surgery aimed at removing the MRI-visible FDL and the part of the hyperperfusion
      cluster within and immediately surrounding the FDL.

PMID- 16981873
TI  - Report of the ILAE classification core group.
AB  - A Core Group of the Task Force on Classification and Terminology has evaluated
      the lists of epileptic seizure types and epilepsy syndromes approved by the
      General Assembly in Buenos Aires in 2001, and considered possible alternative
      systems of classification. No new classification has as yet been proposed.
      Because the 1981 classification of epileptic seizure types, and the 1989
      classification of epilepsy syndromes and epilepsies are generally accepted and
      workable, they will not be discarded unless, and until, clearly better
      classifications have been devised, although periodic modifications to the current
      classifications may be suggested. At this time, however, the Core Group has
      focused on establishing scientifically rigorous criteria for identification of
      specific epileptic seizure types and specific epilepsy syndromes as unique
      diagnostic entities, and is considering an evidence-based approach. The short
      term goal is to present a list of seizure types and syndromes to the ILAE
      Executive Committee for approval as testable working hypotheses, subject to
      verification, falsification, and revision. This report represents completion of
      this work. If sufficient evidence subsequently becomes available to disprove any
      hypothesis, the seizure type or syndrome will be reevaluated and revised or
      discarded, with Executive Committee approval. The recognition of specific seizure
      types and syndromes, as well as any change in classification of seizure types and
      syndromes, therefore, will continue to be an ongoing dynamic process. A major
      purpose of this approach is to identify research necessary to clarify remaining
      issues of uncertainty, and to pave the way for new classifications.

PMID- 16981874
TI  - Increased apparent oral clearance of valproic acid during intake of combined
      contraceptive steroids in women with epilepsy.
AB  - PURPOSE: To determine potential changes in total and unbound serum valproic acid
      (VPA) concentrations at steady-state during a cycle of intake of combined
      hormonal contraceptive (HC) steroids. METHODS: Blood samples were collected from
      nine women stabilized on VPA monotherapy on two separate randomized occasions:
      (i) at the end of the 4- to 7-day HC-free interval, and (ii) on the last day of
      the HC intake period. Trough concentrations of VPA in serum and serum
      ultrafiltrates were determined by fluorescence polarization immunoassay. RESULTS:
      In all women, total and unbound VPA concentrations were higher during the HC-free
      interval than during HC intake (means +/- SD: 425 +/- 184 vs. 350 +/- 145
      micromol/L, respectively, for total VPA, p = 0.002, and 55 +/- 37 vs. 39 +/- 25
      micromol/L, respectively, for unbound VPA, p = 0.005). Compared with the HC-free
      interval, HC intake was associated with a mean 21.5% increase in VPA total
      apparent oral clearance (from 8.0 +/- 5.2 to 9.7 +/- 6.4 ml/h/kg, p = 0.01) and a
      45.2 % increase in VPA unbound apparent oral clearance (from 79 +/- 81 to 115 +/-
      121 ml/h/kg, p = 0.029). CONCLUSIONS: The apparent oral clearance of total and
      unbound VPA increases during the HC intake period compared with the HC-free
      interval, probably due to induction of glucuronosyltransferase by
      ethinylestradiol. The magnitude of the change varies across individuals, being
      potentially clinically relevant in some cases. Serum VPA concentrations should be
      monitored when adding or discontinuing HC steroids, and possibly during the on
      off intervals of a HC cycle.

PMID- 16981875
TI  - Variation in lamotrigine plasma concentrations with hormonal contraceptive
      monthly cycles in patients with epilepsy.
AB  - PURPOSE: This is the first report comparing intrasubject lamotrigine (LTG) plasma
      concentrations between hormonal contraceptive (HC) intake and week-off phases in
      epilepsy patients receiving combined LTG and HC treatment. We describe the
      variation in LTG plasma concentrations with hormonal contraceptive (HC) monthly
      intake cycles in a series of eight patients with epilepsy. METHODS: Venous blood
      samples were prospectively drawn from patients before their first morning dose of
      LTG, once between days 18 and 21 of HC intake and once between days 5 and 7 of
      the HC-free week. RESULTS: Median LTG plasma concentrations were significantly
      higher during the HC washout week than during the phase of HC intake (p = 0.02).
      The median value of intrasubject percentage increase was 27%, with a wide
      interpatient variability. CONCLUSIONS: These findings are in line with a
      preliminary report on healthy volunteers. Standardization of blood sampling in
      relation to HC intake cycles is advisable when planning LTG therapeutic
      monitoring in patients receiving HC.

PMID- 16981876
TI  - Two cases of painful gynecomastia and lower extremity pain in association with
      pregabalin therapy.
AB  - We report two patients with refractory epilepsy who developed unilateral painful
      gynecomastia and lower extremity pain (one of them localized and the other one
      diffuse), shortly after receiving Pregabalin (PGB). Neither of them had previous
      endocrinologic problems or complaints about pain on their medical history. PGB
      was stopped in one patient and reduced in the other one, with complete
      disparition of the symptoms in the following weeks in both patients. This
      supports the hypothesis that gynecomastia could be a drug-induced and easy to
      manage secondary effect of PGB, with a higher incidence than observed on previous
      clinical trials.

PMID- 16981877
TI  - Comparison of reproductive effects of levetiracetam and valproate studied in
      prepubertal porcine ovarian follicular cells.
AB  - PURPOSE: Long-term valproate (VPA) treatment has been associated with
      reproductive endocrine disorders characterized by hyperandrogenism and polycystic
      changes in the ovaries in women with epilepsy. Levetiracetam (LEV) is a
      promising, new antiepileptic drug that may represent an alternative to VPA for
      many patients. Here the effect of LEV and VPA on basal and gonadotropin
      stimulated steroid secretion from prepubertal porcine ovarian follicular cells
      was compared and the conversion of testosterone to estradiol is measured.
      METHODS: Ovarian follicles were obtained from prepubertal pigs. Follicular theca
      and granulosa cells were cocultured and different concentrations of LEV or VPA
      added to the control or gonadotropin-stimulated cultures. RESULTS: VPA, but not
      LEV, caused a significant increase of LH-stimulated testosterone secretion and
      decreased FSH-stimulated estradiol secretion. VPA decreased conversion of
      testosterone to estradiol in both basal and FSH-stimulated cultures, while LEV
      only decreased testosterone to estradiol conversion after FSH stimulation and
      only at the highest, nontherapeutic drug concentration. Both drugs increased
      basal testosterone secretion at therapeutic drug levels. VPA also reduced basal
      estradiol secretion, while LEV decreased basal estradiol secretion only at
      nontherapeutic drug levels. CONCLUSION: Both LEV and VPA affect endocrine
      function in the prepubertal ovary. But while VPA alters both basal and
      gonadotropin-stimulated testosterone and estradiol secretion at therapeutic drug
      concentrations, LEV only affects basal hormone secretion at this concentration
      level. The possibility that LEV could be an alternative treatment to VPA if
      reproductive endocrine problems emerge in adult women, is discussed. However,
      extrapolation to the clinical situation is problematic and particular emphasis is
      placed on the need for further studies.

PMID- 16981880
TI  - Bone metabolism and vitamin D levels in carbamazepine-treated patients.

PMID- 16981881
TI  - Hypermotor seizure arising from insular cortex.

PMID- 16981882
TI  - Proposed diagnostic scheme for the classification of epileptic seizures and
      epilepsies (ILAE, 2001): proposal from Japan Epilepsy Society.

PMID- 16981884
TI  - Interventions to prevent venous thrombosis after air travel: are they necessary?
      No.

PMID- 16981885
TI  - Anticoagulation therapy after recent bleeding: is it ever safe?

PMID- 16981886
TI  - Prothrombin A19911G polymorphism and the risk of venous thromboembolism.
AB  - BACKGROUND: The A > G polymorphism at position 19911 of the prothrombin gene is
      associated with increased plasma prothrombin levels but its role as a risk factor
      for venous thromboembolism (VTE) is not established. OBJECTIVE: To investigate
      the role of prothrombin 19911 A > G polymorphism in the risk of VTE in patients
      with heterozygous prothrombin 20210GA or factor (F) V Leiden and in those without
      thrombophilia. PATIENTS AND METHODS: Case-control study of 793 patients with
      prothrombin 20210 GA (n = 167) or FV Leiden (n = 198), and without thrombophilia
      (n = 428), and of 795 healthy individuals with the corresponding coagulation
      profile, investigated for the presence of prothrombin 19911 A > G. Plasma
      prothrombin levels were measured in 342 individuals. RESULTS: Prothrombin 19911 A
      > G did not increase the risk of VTE in carriers of prothrombin 20210 GA [odds
      ratio (OR) 1.2, 95% CI (95% CI) 0.8-1.8] but significantly increased the risk in
      carriers of FV Leiden (OR 2.1, 95% CI 1.3-3.4) and in patients without
      thrombophilia (OR 1.5, 95% CI 1.0-2.2). Higher plasma prothrombin levels in
      carriers of prothrombin 19911 A > G polymorphism than in non-carriers were found
      among individuals without thrombophilia (P =0.05) and with FV Leiden (P = 0.07),
      but not in carriers of prothrombin 20210 GA (P = 0.2). CONCLUSIONS: Prothrombin
      19911 A > G polymorphism was independently associated with a 1.5-fold increased
      risk of VTE and increased 2-fold the risk of VTE associated with FV Leiden, both
      increases statistically significant. No effect was observed in carriers of
      prothrombin 20210 GA, perhaps because this polymorphism has a stronger influence
      on plasma prothrombin levels than the prothrombin 19911 polymorphism.

PMID- 16981887
TI  - Is protein C inhibitor antithrombotic and protective in pulmonary hypertension?

PMID- 16981888
TI  - More on: incorrect use of thromboprophylaxis for venous thromboembolism in
      medical and surgical patients: results of a multicentric, observational, and
      cross-sectional study in Brazil.

PMID- 16981889
TI  - A nicotinic acetylcholine receptor mutation (Y151S) causes reduced agonist
      potency to a range of neonicotinoid insecticides.
AB  - Neonicotinoid insecticides are potent selective agonists of insect nicotinic
      acetylcholine receptors (nAChRs). Since their introduction in 1991, resistance to
      neonicotinoids has been slow to develop, but it is now established in some insect
      field populations such as the planthopper, Nilaparvata lugens, a major rice pest
      in many parts of Asia. We have reported recently the identification of a target
      site mutation (Y151S) within two nAChR subunits (Nlalpha1 and Nlalpha3) from a
      laboratory-selected field population of N. lugens. In the present study, we have
      examined the influence of this mutation upon the functional properties of
      recombinant nAChRs expressed in Xenopus oocytes (as hybrid nAChRs, co-expressed
      with a rat beta2 subunit). The agonist potency of several nicotinic agonists has
      been examined, including all of the neonicotinoid insecticides that are currently
      licensed for either crop protection or animal health applications (acetamiprid,
      clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid and
      thiamethoxam). The Y151S mutation was found to have no significant effect on the
      maximal current (I(max)) observed with the endogenous agonist, acetylcholine. In
      contrast, a significant reduction in I(max) was observed for all neonicotinoids
      (the I(max) for mutant nAChRs ranged from 13 to 81% of that observed on wild-type
      receptors). In addition, nAChRs containing the Y151S mutation caused a
      significant rightward shift in agonist dose-response curves for all
      neonicotinoids, but of varying magnitude (shifts in EC(50) values ranged from 1.3
      to 3.6-fold). The relationship between neonicotinoid structure and their potency
      on nAChRs containing the Y151S target-site mutation is discussed.

PMID- 16981890
TI  - The age-related attenuation in long-term potentiation is associated with
      microglial activation.
AB  - It is well established that inflammatory changes contribute to brain ageing, and
      an increased concentration of proinflammatory cytokine, interleukin-1beta (IL
      1beta), has been reported in the aged brain associated with a deficit in long
      term potentiation (LTP) in rat hippocampus. The precise age at which changes are
      initiated is unclear. In this study, we investigate parallel changes in markers
      of inflammation and LTP in 3-, 9- and 15-month-old rats. We report evidence of
      increased hippocampal concentrations of the proinflammatory cytokines IL-1alpha,
      IL-18 and interferon-gamma (IFNgamma), which are accompanied by deficits in LTP
      in the older rats. We also show an increase in expression of markers of
      microglial activation, CD86, CD40 and intercellular adhesion molecules (ICAM).
      Associated with these changes, we observed a significant impairment of
      hippocampal LTP in the same rats. The importance of microglial activation in the
      attenuation of long-term potentiation (LTP) was demonstrated using an inhibitor
      of microglial activation, minocycline; partial restoration of LTP in 15-month-old
      rats was observed following administration of minocycline. We propose that signs
      of neuroinflammation are observed in middle age and that these changes, which are
      characterized by microglial activation, may be triggered by IL-18.

PMID- 16981891
TI  - Temporal coupling of cyclic AMP and Ca/calmodulin-stimulated adenylyl cyclase to
      the circadian clock in chick retinal photoreceptor cells.
AB  - cAMP signaling pathways play crucial roles in photoreceptor cells and other
      retinal cell types. Previous studies demonstrated a circadian rhythm of cAMP
      level in chick photoreceptor cell cultures that drives the rhythm of activity of
      the melatonin synthesizing enzyme arylalkylamine N-acetyltransferase and the
      rhythm of affinity of the cyclic nucleotide-gated channel for cGMP. Here, we
      report that the photoreceptor circadian clock generates a rhythm in
      Ca(2+)/calmodulin-stimulated adenylyl cyclase activity, which accounts for the
      temporal changes in the cAMP levels in the photoreceptors. The circadian rhythm
      of cAMP in photoreceptor cell cultures is abolished by treatment with the l-type
      Ca(2+) channel antagonist nitrendipine, while the Ca(2+) channel agonist, Bay K
      8644, increased cAMP levels with continued circadian rhythmicity in constant
      darkness. These results indicate that the circadian rhythm of cAMP is dependent,
      in part, on Ca(2+) influx. Photoreceptor cell cultures exhibit a circadian rhythm
      in Ca(2+)/calmodulin-stimulated adenylyl cyclase enzyme activity with high levels
      at night and low levels during the day, correlating with the temporal changes of
      cAMP in these cells. Transcripts encoding two of the Ca(2+)/calmodulin-stimulated
      adenylyl cyclases, type 1 and type 8 (Adcy1 and Adcy8), displayed significant
      daily rhythms of mRNA expression under a light-dark cycle, but only the Adcy1
      transcript rhythm persisted in constant darkness. Similar rhythms of Adcy1 mRNA
      level and Ca(2+)/calmodulin-stimulated adenylyl cyclase activity were observed in
      retinas of 2-week-old chickens. These results indicate that a circadian clock
      controls the expression of Adcy1 mRNA and Ca(2+)/calmodulin-stimulated adenylyl
      cyclase activity; and calcium influx into these cells gates the circadian rhythm
      of cAMP, a key component in the regulation of photoreceptor function.

PMID- 16981892
TI  - Isoform- and subcellular fraction-specific differences in hippocampal 14-3-3
      levels following experimentally evoked seizures and in human temporal lobe
      epilepsy.
AB  - 14-3-3 proteins are a family of signaling molecules involved in diverse cellular
      functions, which can mediate anti-apoptotic effects. Seizure-induced neuronal
      death may involve programmed (apoptotic) cell death pathways and is associated
      with a decline in brain 14-3-3 levels. Presently, we investigated the subcellular
      localization and effects of seizures on isoforms of 14-3-3 in rat hippocampus,
      and contrasted these to findings in human temporal lobe epilepsy (TLE). All brain
      isoforms of 14-3-3 were detected in the cytoplasmic compartment of rat
      hippocampus, while 14-3-3gamma and -zeta were also present in mitochondrial and
      microsome-enriched fractions. Focally evoked seizures in rats significantly
      reduced 14-3-3gamma levels within the microsome-enriched compartment at 4 h, with
      similar responses for 14-3-3zeta, while cytoplasm-localized 14-3-3beta, -epsilon
      and -eta remained unchanged. Analysis of human autopsy control hippocampus
      revealed similar 14-3-3 isoform expression profiles. In TLE samples, the
      microsome-enriched fraction also showed differences, but here 14-3-3epsilon and 
      zeta levels were higher than controls. TLE sample 14-3-3 isoform abundance within
      the cytoplasmic fraction was not different to controls. This study defines the
      subcellular localization of 14-3-3 isoforms in rat and human hippocampus and
      identifies the microsome-enriched fraction as the main site of altered 14-3-3
      levels in response to acute prolonged and chronic recurrent seizures.

PMID- 16981893
TI  - Ontogeny of brain and blood serotonin levels in 5-HT receptor knockout mice:
      potential relevance to the neurobiology of autism.
AB  - The most consistent neurochemical finding in autism has been elevated group mean
      levels of blood platelet 5-hydroxytryptamine (5-HT, serotonin). The origin and
      significance of this platelet hyperserotonemia remain poorly understood. The 5
      HT(1A) receptor plays important roles in the developing brain and is also
      expressed in the gut, the main source of platelet 5-HT. Post-natal tissue levels
      of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan were examined in the
      brain, duodenum and blood of 5-HT(1A) receptor-knockout and wild-type mice. At 3
      days after birth, the knockout mice had lower mean brain 5-HT levels and normal
      mean platelet 5-HT levels. Also, at 3 days after birth, the mean tryptophan
      levels in the brain, duodenum and blood of the knockout mice were around 30%
      lower than those of the wild-type mice. By 2 weeks after birth, the mean brain 5
      HT levels of the knockout mice normalized, but their mean platelet 5-HT levels
      became 24% higher than normal. The possible causes of these dynamic shifts were
      explored by examining correlations between central and peripheral levels of 5-HT,
      5-HIAA and tryptophan. The results are discussed in relation to the possible role
      of 5-HT in the ontogeny of autism.

PMID- 16981894
TI  - Alpha-synuclein inhibits aromatic amino acid decarboxylase activity in
      dopaminergic cells.
AB  - Alpha-synuclein is a presynaptic protein strongly implicated in Parkinson's
      disease (PD). Because dopamine neurons are invariably compromised during
      pathogenesis in PD, we have been exploring the functions of alpha-synuclein with
      particular relevance to dopaminergic neuronal cells. We previously discovered
      reduced tyrosine hydroxylase (TH) activity and minimal dopamine synthesis in
      stably-transfected MN9D cells overexpressing either wild-type or A53T mutant
      (alanine to threonine at amino acid 53) alpha-synuclein. TH, the rate-limiting
      enzyme in dopamine synthesis, converts tyrosine to l-dihydroxyphenylalanine (L
      DOPA), which is then converted to dopamine by the enzyme, aromatic amino acid
      decarboxylase (AADC). We confirmed an interaction between alpha-synuclein and
      AADC in striatum. We then sought to determine whether wild-type or A53T mutant
      alpha-synuclein might have affected AADC activity in dopaminergic cells. Using
      HPLC with electrochemical detection, we measured dopamine and related catechols
      after L-DOPA treatments to bypass the TH step. We discovered that while alpha
      synuclein did not reduce AADC protein levels, it significantly reduced AADC
      activity and phosphorylation in our cells. These novel findings further support a
      role for alpha-synuclein in dopamine homeostasis and may explain, at least in
      part, the selective vulnerability of dopamine neurons that occurs in PD.

PMID- 16981895
TI  - Effect of hypoxia on the transcription pattern of subunit isoforms and the
      kinetics of cytochrome c oxidase in cortical astrocytes and cerebellar neurons.
AB  - Brain energy metabolism essentially depends on the availability of oxygen
      representing the energetic substrate for cytochrome c oxidase (COX). The
      catalytic activity of mammalian COX is regulated by binding of ATP to the N
      terminus of subunit IV. This causes an allosteric inhibition of the enzyme at a
      high energy level and thus plays an important role in adjusting energy production
      to cellular energy requirements. We have studied COX activity in cortical
      astrocytes and cerebellar granule cells after normoxia and hypoxia treatment.
      Differences in the kinetic behaviour of COX from these two brain cell types can
      be addressed to a differential, but cell type-specific, expression of the COX
      subunit IV-2 isoform. Besides COX isoform IV-1, which is ubiquitously transcribed
      in all mammalian tissues, we also detected low levels of COX isoform IV-2 in
      cerebellar neurons, but not in cortical astrocytes. Under conditions of oxygen
      deprivation, transcription of COX IV-2 is induced in astrocytes and further up
      regulated in cerebellar granule cells. Elevated transcription levels of the COX
      IV-2 isoform are accompanied by an abolition of the allosteric inhibition of COX
      by ATP. We conclude that the presence of the COX isoform IV-2 suppresses the
      sensitivity of COX to its allosteric regulator ATP and overrules the regulation
      of COX by the cellular energy level. This suggests a pivotal role of COX as an
      oxygen sensor for brain function.

PMID- 16981896
TI  - Distribution of the FcgammaRIIIa 176 F/V polymorphism amongst healthy Chinese,
      Malays and Asian Indians in Singapore.
AB  - AIMS: To determine and compare the distribution of the FcgammaRIIIa 176 F/V
      polymorphism across three ethnically distinct populations (Chinese, Asian Indians
      and Malays) in Singapore. METHODS: The FcgammaRIIIa 176 F/V polymorphism was
      genotyped by direct sequencing from genomic DNA samples obtained from normal
      healthy Chinese, Asian Indians and Malays (n = 192 from each population).
      RESULTS: The allelic frequencies of the high binding affinity FcgammaRIIIa 176 V
      allele for Chinese, Asian Indians and Malays were 35%, 33% and 46%, respectively
      (F allele frequencies were 65%, 67% and 54%, respectively). Genotype
      distributions were found to conform to the Hardy-Weinberg law (P > 0.05) in each
      group. chi(2) comparisons revealed significant differences in the genotype
      distributions of the FcgammaRIIIa 176 V/F polymorphism of Malays from the other
      two populations (Chinese and Asian Indians). However, no significant difference
      in the genotype distributions of the FcgammaRIIIa 176 V/F polymorphism was
      observed between Chinese and Asian Indian populations. CONCLUSIONS: The genotype
      distributions of the FcgammaRIIIa 176 V/F polymorphism in healthy Malays are
      significantly different from both Chinese and Indians. These observations provide
      the fundamentals on which future disease associations may be built and also
      present important implications for the design of therapeutic regimens amongst
      various ethnic groups.

PMID- 16981897
TI  - Effect of 2% dorzolamide on retinal blood flow: a study on juvenile primary open
      angle glaucoma patients already receiving 0.5% timolol.
AB  - AIM: To investigate whether dorzolamide modifies peripapillary retinal
      haemodynamics in juvenile primary open-angle glaucoma (JPOAG) patients treated
      with timolol. METHODS: In 40 JPOAG subjects, before and after dorzolamide
      coadministration with timolol, the following examinations were achieved:
      intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP),
      heart rate (HR), visual field and retinal flowmetry. RESULTS: Adjunctive therapy
      with dorzolamide induced the following modifications: IOP reduction [1.75 mmHg,
      95% confidence interval (CI) 1.23, 2.26; P < 0.05], OPP increase (5.09 mmHg, 95%
      CI 2.97, 7.20; P < 0.02) and retinal blood flow improvement (35.0 arbitrary
      units, 95% CI 12.20, 57.80; P < 0.03). BP, HR and visual field indices did not
      change. CONCLUSIONS: Dorzolamide, in association or in fixed combination with
      timolol, significantly improves retinal blood flow in JPOAG patients.

PMID- 16981898
TI  - Differential protein binding of indinavir and saquinavir in matched maternal and
      umbilical cord plasma.
AB  - AIMS: To determine whether lower umbilical cord than maternal binding of
      indinavir and saquinavir contributed to the low cord : maternal (C : M) total
      concentration ratios reported previously. METHODS: Indinavir and saquinavir
      unbound fraction (fu) was determined using equilibrium dialysis. Buffer solutions
      of human serum albumin (HSA) (20.0, 30.0, 40.0 g l(-1)) and alpha(1)-acid
      glycoprotein (AAG) (0.20, 0.60, 2.00 g l(-1)) were spiked with indinavir (1.00
      and 8.00 mg l(-1)) or saquinavir (0.15 and 1.50 mg l(-1)). Matched maternal and
      umbilical cord plasma was spiked with 1.00 mg l(-1) indinavir (n = 12) or 0.15 mg
      l(-1) saquinavir (n = 20). Spiked protein/plasma solutions were dialyzed against
      isotonic phosphate buffer, at 37 degrees C. At equilibrium, indinavir and
      saquinavir concentrations were quantified, and the f(u) determined. RESULTS:
      Indinavir and saquinavir demonstrated protein concentration-dependent binding in
      buffer solutions of HSA and AAG. Indinavir f(u) was significantly higher in
      umbilical cord (0.53 +/- 0.12) compared with maternal (0.36 +/- 0.11) plasma (95%
      CI of the difference -0.26, -0.097). Similarly, saquinavir fu was different
      between umbilical cord (0.0090 +/- 0.0046) and maternal plasma (0.0066 +/-
      0.0039) (95% CI of the difference -0.0032, -0.0016). The transplacental AAG
      concentration gradient contributed significantly to the binding differential of
      both drugs. CONCLUSIONS: The differential plasma binding of both drugs, which was
      largely the result of the transplacental AAG concentration gradient, would
      contribute to the low C : M total plasma concentration ratios observed
      previously. Unbound concentrations of indinavir and saquinavir are likely to be
      substantially lower in umbilical cord than maternal plasma.

PMID- 16981899
TI  - Adrenal axis suppression unrelated to the dynamics of dosing with beclomethasone
      monopropionate.
AB  - AIMS: Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment. At
      high doses they can give rise to systemic side-effects such as hypothalamic
      pituitary-adrenal (HPA) axis suppression. This effect may depend on the delivery
      system, which in turn alters drug deposition and adsorption. We hypothesized that
      adrenal suppression depends on the rate of steroid absorption rather than the
      total steroid dose received. METHODS: Eight healthy adult males were recruited
      for a randomized double-blind placebo controlled trial. Adrenocortical
      suppression ability was demonstrated by a 30% suppression of early morning
      cortisol following 1 mg dexamethasone. Subjects then attended in the evening on
      two occasions receiving 500 microg of intravenous beclomethasone monopropionate
      (17-BMP) for either 15 min or 2 h. Overnight urinary cortisol : creatinine (C :
      C) ratio was measured before and after the infusion and an 08.00 h serum cortisol
      was measured following the infusion. RESULTS: Mean C : C pre and post 15 min
      infusion was 5.97 and 3.22 (P = 0.005). Mean C : C pre and post 2 h infusion was
      6.31 and 4.15 (P = 0.004). Delta C : C and mean 08.00 h cortisol for 15 min and 2
      h infusion was 2.74 and 2.16 and 425 nmol l(-1) and 400 nmol l(-1), respectively
      (P = NS). CONCLUSIONS: The rate of infusion of 17-BMP seemed to have little
      effect on the degree of adrenal suppression. Individual C : C ratios were
      reproducible. Differences in absorption of ICS are unlikely to explain observed
      differences in HPA axis suppression.

PMID- 16981901
TI  - Lack of a pharmacokinetic interaction between steady-state roflumilast and single
      dose midazolam in healthy subjects.
AB  - AIMS: The aim of this study was to investigate the effects of roflumilast, an
      investigational PDE4 inhibitor for the treatment of COPD and asthma, on the
      pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites.
      METHODS: In an open, randomized (for midazolam treatment sequence) study, 18
      healthy male subjects received single doses of midazolam (2 mg oral and 1 mg
      i.v., 1 day apart) alone, repeated doses of roflumilast (500 microg once daily
      for 14 days) alone, and repeated doses of roflumilast together with single doses
      of midazolam (2 mg oral and 1 mg i.v., 1 day apart). RESULTS: A comparison of
      clearance and peak and systemic exposure to midazolam following administration of
      roflumilast indicated no effect of roflumilast dosed to steady state on the
      pharmacokinetics of midazolam. Point estimates (90% CI) were 0.97 (0.84, 1.13)
      for the AUC of i.v. midazolam and 0.98 (0.82, 1.17) for that of oral midazolam
      with and without roflumilast. CONCLUSIONS: Therapeutic steady state
      concentrations of roflumilast and its N-oxide do not alter the disposition of the
      CYP3A substrate midazolam in healthy subjects. This finding suggests that
      roflumilast is unlikely to alter the clearance of drugs that are metabolized by
      CYP3A4.

PMID- 16981900
TI  - Effect of multiple doses of montelukast on the pharmacokinetics of rosiglitazone,
      a CYP2C8 substrate, in humans.
AB  - AIMS: To investigate the effect of multiple dosing with montelukast, a selective
      leukotriene-receptor antagonist, on the pharmacokinetics of rosiglitazone, a
      CYP2C8 substrate, in humans. METHODS: A two-period, randomized crossover study
      was conducted in 10 healthy subjects. After administration of oral doses of
      placebo or 10 mg montelukast daily for 6 days, 4 mg rosiglitazone was
      administered and plasma samples were obtained for 24 h and analyzed for
      rosiglitazone and N-desmethylrosiglitazone using high-performance liquid
      chromatography with fluorescence detection. RESULTS: During the montelukast
      phase, the total area under the time-concentration curve (AUC) and peak plasma
      concentration of rosiglitazone were 102% (90% CI 98, 107%) and 98% (90% CI 92,
      103%) of the corresponding values during the placebo phase, respectively.
      Multiple dosing with montelukast did not affect the oral clearance of
      rosiglitazone significantly (90% CI 94, 105%; P = 0.50). The AUC ratio and plasma
      concentration ratios of N-desmethylrosiglitazone : rosiglitazone were not changed
      by multiple dosing with montelukast (90% CI 90, 103%; P = 0.14). CONCLUSIONS:
      Multiple doses of montelukast do not inhibit CYP2C8-mediated rosiglitazone
      metabolism in vivo despite in vitro findings indicating that montelukast is a
      selective CYP2C8 inhibitor.

PMID- 16981902
TI  - Chemotherapy for older patients with prostate cancer.

PMID- 16981903
TI  - Chitosomes: past, present and future.
AB  - Jose Ruiz-Herrera's discovery that chitin microfibrils could be made by a fungal
      extract paved the way for elucidating the intracellular location of chitin
      synthetase. In collaboration with Charles Bracker, chitosomes were identified as
      the major reservoir of chitin synthetase in fungi. Unique in size, buoyant
      density, and membrane thickness, chitosomes were found in a wide range of fungi.
      Their reversible dissociation into 16S subunits is another unique property of
      chitosomes. These 16S subunits are the smallest molecular entities known to
      retain chitin synthetase activity. Further dissociation leads to complete loss of
      activity. From studies with secretory mutants, yeast researchers concluded that
      chitosomes were components of the endocytosis pathway. However, key structural
      and enzymatic characteristics argue in favor of the chitosome being poised for
      exocytotic delivery rather than endocytotic recycling. The chitosome represents
      the main vehicle for delivering chitin synthetase to the cell surface. An
      immediate challenge is to elucidate chitosome ontogeny and the role of proteins
      encoded by the reported chitin synthetase genes in the structure or function of
      chitosomes. The ultimate challenge would be to understand how the chitosome
      integrates with the cell surface to construct the organized microfibrillar
      skeleton of the fungal cell wall.

PMID- 16981904
TI  - Cell density- and ComE-dependent expression of a group of mutacin and mutacin
      like genes in Streptococcus mutans.
AB  - Streptococcus mutans is a major cariogenic inhabitant of the high cell density
      oral biofilm (dental plaque). In previous studies, we showed that production of
      one of its virulence factors, the bacteriocin mutacin IV, was regulated by high
      cell density as well as the competence regulatory system ComED. In this study, we
      utilized luciferase fusions and real-time reverse transcriptase polymerase chain
      reaction (RT-PCR), to demonstrate that high cell density and ComED also regulate
      an uncharacterized group of mutacin and mutacin-like genes. Under high cell
      density or in the presence of externally added competence-stimulating peptide
      (CSP), gene expression increased 10- to 30-fold. Interestingly, high cell density
      was able to bypass the requirement for CSP addition. However, both cell density
      and CSP-dependent gene expression had a strict requirement for the ComE response
      regulator.

PMID- 16981905
TI  - Osteoprotegerin protects endothelial cells against apoptotic cell death induced
      by Porphyromonas gingivalis cysteine proteinases.
AB  - Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis during the
      progression of periodontitis. Recent reports suggest that osteoprotegerin may
      also prevent arterial calcification and contribute to endothelial cell survival.
      To determine whether the vascular functions of osteoprotegerin are involved in
      periodontitis, we examined whether osteoprotegerin contributed to the survival of
      endothelial cells damaged by Porphyromonas gingivalis cysteine proteinases
      (gingipains). Gingipain proteinases cleave a broad range of host proteins, and
      are important virulence factors of P. gingivalis, a major causative bacterium of
      adult periodontitis. Human microvascular endothelial cells (HMVEC) were exposed
      to activated gingipain extracts from P. gingivalis 381, with and without
      pretreatment with osteoprotegerin. Cell viability was quantified by the
      tetrazolium (WST-8) reduction assay, and apoptosis was examined using Hoechst
      33342 nuclear staining. After 16 h of treatment with activated gingipain
      extracts, HMVEC showed near-complete detachment from the tissue culture dish, and
      apoptosis was evident by 24 h. Pretreatment of HMVEC with osteoprotegerin reduced
      the extent of both cellular detachment and apoptotic cell death. Our results
      indicated that osteoprotegerin pretreatment protected HMVEC against detachment
      and apoptotic cell death induced by gingipain-active bacterial cell extracts.
      These results also suggest that osteoprotegerin may function as a survival factor
      for endothelial cells during periodontitis.

PMID- 16981906
TI  - Carotid artery haemorrhage: an uncommon complication of constipation in a patient
      with severe haemophilia A.

PMID- 16981907
TI  - A functional polymorphism of apolipoprotein C1 detected by mass spectrometry.
AB  - A survey of plasma proteins in approximately 1,300 individuals by MALDI-TOF MS
      resulted in identification of a structural polymorphism of apolipoprotein C1
      (ApoC1) that was found only in persons of American Indian or Mexican ancestry.
      MS/MS analysis revealed that the alteration consisted of a T45S variation. The
      methyl group of T45 forms part of the lipid-interacting surface of ApoC1. In
      agreement with an impact on lipid contact, the S45 variant was more susceptible
      to N-terminal truncation by dipeptidylpeptidase IV in vitro than was the T45
      variant. The S45 protein also displayed greater N-terminal truncation (loss of
      Thr-Pro) in vivo than the T45 variant. The S45 variant also showed preferential
      distribution to the very-low-density lipoprotein fraction than the T45 protein.
      These properties indicate a functional effect of the S45 variant and support a
      role for residue 45 in lipid contact and lipid specificity. Further studies are
      needed to determine the effects of the variant and its altered N-terminal
      truncation on the metabolic functions of ApoC1.

PMID- 16981908
TI  - DNA modification with cisplatin affects sequence-specific DNA binding of p53 and
      p73 proteins in a target site-dependent manner.
AB  - Proteins p53 and p73 act as transcription factors in cell cycle control,
      regulation of cell development and/or in apoptotic pathways. Both proteins bind
      to response elements (p53 DNA-binding sites), typically consisting of two copies
      of a motif RRRCWWGYYY. It has been demonstrated previously that DNA modification
      with the antitumor drug cisplatin inhibits p53 binding to a synthetic p53 DNA
      binding site. Here we demonstrate that the effects of global DNA modification
      with cisplatin on binding of the p53 or p73 proteins to various p53 DNA-binding
      sites differed significantly, depending on the nucleotide sequence of the given
      target site. The relative sensitivities of protein-DNA binding to cisplatin DNA
      treatment correlated with the occurrence of sequence motifs forming stable
      bifunctional adducts with the drug (namely, GG and AG doublets) within the target
      sites. Binding of both proteins to mutated p53 DNA-binding sites from which these
      motifs had been eliminated was only negligibly affected by cisplatin treatment,
      suggesting that formation of the cisplatin adducts within the target sites was
      primarily responsible for inhibition of the p53 or p73 sequence-specific DNA
      binding. Distinct effects of cisplatin DNA modification on the recognition of
      different response elements by the p53 family proteins may have impacts on
      regulation pathways in cisplatin-treated cells.

PMID- 16981909
TI  - The immunohistochemical expression of CD34 in human hair follicles: a comparative
      study with the bulge marker CK15.
AB  - BACKGROUND: Anti-CD34 antibodies label the bulge region of mouse hair follicles.
      However, in human hair follicles, CD34 immunoreactivity is found in the outer
      root sheath below the bulge zone. The immunohistochemical staining of CD34 in
      catagen and telogen follicles has not been evaluated. AIMS: To characterize the
      expression of CD34 immunoreactivity at different stages of the hair cycle in
      human terminal hair follicles, and to compare the immunostaining pattern of CD34
      with that of CK15, used here as a marker of the bulge region. METHOD: Serial
      vertical sections of human hair follicles in anagen, catagen and telogen phases
      were immunostained with anti-CD34 (QBEnd 10) and anti-CK15 (LHK15 and C8/144B)
      antibodies. Double-labelling immunofluorescence was also performed. RESULTS: The
      catagen and telogen follicles studied did not show CD34 immunoreactivity in the
      outer root sheath. The location of CD34 and CK15 immunoreactivity in anagen
      follicles reveals a different staining pattern: CD34-positive cells are located
      in the outer root sheath below the attachment zone of the arrector pili muscle,
      whereas CK15-positive cells are located in the outer root sheath above the
      attachment zone of the arrector pili muscle. CONCLUSIONS: Only anagen human hair
      follicles show CD34 immunoreactivity. CD34 and CK15 recognize different types of
      cells or cells at different stages of differentiation.

PMID- 16981910
TI  - Antiangiogenic and immunomodulatory effects of rapamycin on islet endothelium:
      relevance for islet transplantation.
AB  - Donor intra-islet endothelial cells contribute to neovascularization after
      transplantation. Several factors may interfere with this process and ultimately
      influence islet engraftment. Rapamycin, a central immunosuppressant in islet
      transplantation, is an mTOR inhibitor that has been shown to inhibit cancer
      angiogenesis. The aim of this study was to evaluate the effects of rapamycin on
      islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from
      freshly purified human islets and the formation of capillary-like structures in
      vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID
      mice. Rapamycin decreased migration, proliferation and angiogenic properties of
      human and mouse islet-derived endothelial cell lines with appearance of
      apoptosis. The expression of angiogenesis-related factors VEGF, alphaVbeta3
      integrin and thrombospondin-1 on islet endothelium was altered in the presence of
      rapamycin. On the other hand, rapamycin decreased the surface expression of
      molecules involved in immune processes such as ICAM-1 and CD40 and reduced the
      adhesion of T cells to islet endothelium. Our results suggest that rapamycin
      exerts dual effects on islet endothelium inducing a simultaneous inhibition of
      angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion
      and activation.

PMID- 16981911
TI  - Utilizing list exchange and nondirected donation through 'chain' paired kidney
      donations.
AB  - In a list exchange (LE), the intended recipient in an incompatible pair receives
      priority on the deceased donor waitlist (DD-waitlist) after the paired
      incompatible donor donates a kidney to a DD-waitlist candidate. A nondirected
      donor's (ND-D) kidney is usually transplanted directly to a DD-waitlist
      candidate. These two established practices would help even more transplant
      candidates if they were integrated with kidney paired donation (KPD). We consider
      a scenario in which the donor of an LE intended recipient (LE-IR) donates to a
      compatible KPD intended recipient (KPD-IR), and the KPD donor (KPD-D) donates to
      the waitlist (an LE-chain). We consider a similar scenario in which an ND-D
      donates to a KPD-IR and the KPD-D donates to the DD-waitlist (an ND-chain). Using
      data derived from the New England Program for Kidney Exchange (NEPKE) and from
      OPTN/SRTR recipient-donor distributions, simulations are presented to evaluate
      the potential impact of chain exchanges coordinated with KPD. LE donors (LE-D)
      and ND-D who are ABO-O result in the highest number of additional transplants,
      while results for ABO-A and B donors are similar to each other. We recommend that
      both LE and ND donations be utilized through chain exchanges.

PMID- 16981912
TI  - BRIEF REPORT: health care provided by program directors to their resident
      physicians and families.
AB  - BACKGROUND: Who provides health care to resident physicians is not well studied.
      OBJECTIVE: To determine whether residency program directors (PDs)provide health
      care to their own residents and residents' families. DESIGN: An anonymous survey
      mailed to 1,345 PDs in Emergency Medicine, Family Medicine, Internal Medicine,
      Medicine-Pediatrics,and Obstetrics-Gynecology in the United States in 2003.
      RESULTS: Six hundred nineteen PDs (46%) responded. Half had taken care of their
      own residents for acute conditions. Less commonly, directors had written
      prescriptions for acute (40%) or chronic needs (15%}or provided ongoing care
      (22%). Only 3% believed this conflicted with their ability to be effective
      directors. Responders more likely to provide future care to residents considered
      this kind of care generally appropriate(P< .001), or appropriate under certain
      circumstances {P< .001).Most of these spent > 31% of their time seeing patients.
      There was no difference among types of programs, gender of the director, or the
      years as director. Twenty-five percent of directors provided care to their
      residents' families. CONCLUSIONS: Substantial numbers of directors provided
      healthcare to their own residents. Few believed this conflicted with their
      director role. We believe organizations of PDs should develop positions about
      this practice.

PMID- 16981913
TI  - Confusing ICD terminology: refractory and blanking periods.

PMID- 16981914
TI  - Influence of drive cycle length on initiation of ventricular fibrillation during
      implantable cardioverter defibrillator threshold testing.
AB  - BACKGROUND: Programmed electrical stimulation of the heart as a method to induce
      tachyarrhythmias has been described since the 1960s. To date, no study has
      examined optimal drive cycle length in the induction of ventricular fibrillation
      (VF) during defibrillation threshold testing after implantable cardioverter
      defibrillator placement. We hypothesized that longer drive cycle length, by means
      of the longer action potential duration, would promote intramyocardial phase 2
      reentry and facilitate induction of VF. METHODS: Fifty consecutive implants were
      randomized in a prospective crossover format for this study. The group consisted
      of 40 men and 10 women, with each patient receiving either a 400 or 600 ms
      initial drive train prior to 1.2 J internal shock on the T wave with a goal to
      induce ventricular fibrillation. The timing of the T wave shock was determined by
      measuring the interval from the beginning of the QRS to the apex of the T wave in
      lead II. Successful inductions were defibrillated via the cardioverter
      defibrillator. Patients were then crossed over and the protocol repeated.
      RESULTS: Twenty of 23 (87%) patients were successfully induced into VF in the
      initial 400 ms drive train arm whereas 22 of 27 (81%) were successfully induced
      in the 600 ms arm. Thus, a total of 44 (88%) patients were successfully induced
      at 400 ms, 41 (82%) patients were successfully induced at 600 ms, and 2 (4%)
      patients were not inducible at either cycle length, but were inducible with 50 Hz
      ventricular stimulation. However, no significant difference was noted between the
      two groups. CONCLUSION: No investigation to date has questioned whether a
      relationship exists between drive cycle length and initiation of ventricular
      fibrillation. Our study addresses this question, though negative for difference
      between 400 and 600 ms drive trains. Further research into optimal strategies for
      inducing ventricular fibrillation will minimize patient sedation time and
      discomfort while undergoing defibrillator threshold testing.

PMID- 16981915
TI  - A pilot study examining the performance of polynomial-modeled ventricular shock
      electrograms for rhythm discrimination in implantable devices.
AB  - BACKGROUND: Inappropriate shocks continue to be a problem for patients with
      implantable defibrillators (ICD). We evaluated the performance of polynomial
      modeled ventricular electrograms (EGM) to discriminate between supraventricular
      tachycardia (SVT) and ventricular tachycardia (VT). METHODS: Seven sets of EGM
      from patients having both SVT and VT documented during a single ICD interrogation
      were included. The cardiac cycle was analyzed off-line in two parts, QR and RQ
      segments, which were modeled separately using third-order and sixth-order
      polynomial equations, respectively. These segments were then analyzed to
      determine which polynomial coefficients were most significant for rhythm
      discrimination. RESULTS: When analyzing the QR segment during arrhythmia, there
      were statistically significant (P<0.05) correlations in 4 of 4 (100%) of the QR
      coefficients when comparing normal sinus rhythm (NSR) to SVT and 2 of 4 (50%)
      when comparing NSR to VT or SVT to VT. When analyzing the RQ segment during
      arrhythmia, there were statistically significant (P<0.05) correlations in 4 of 7
      (57%) of the RQ coefficients when comparing NSR to SVT, 5 of 7 (71%) when
      comparing NSR to VT, and 3 of 7 (43%) when comparing SVT to VT. Using a cutoff
      value of 50% change from NSR, the ratio of first-order to zero-order QR
      coefficient was able to completely separate VT from SVT (P=0.03) in this series
      of patients. CONCLUSION: Our data demonstrate the feasibility of simple
      polynomial equations that reproduce the depolarization and repolarization phases
      of human ventricular shock EGM. The ratio of first-order to zero-order QR
      coefficient was able to reliably discriminate between SVT and VT while reducing
      the polynomial model to a first-order system. The results of this pilot trial may
      serve as the basis for a larger prospective trial implementing a discrimination
      algorithm for use in low computational power implantable devices.

PMID- 16981916
TI  - Anodal capture in cardiac resynchronization therapy implications for device
      programming.
AB  - INTRODUCTION: Right ventricular (RV) anodal capture (AC) has been reported in
      cardiac resynchronization therapy (CRT), when left ventricular (LV) pacing uses
      pseudobipolar (LV tip to RV proximal electrode) configuration. The aim of the
      study was to analyze the prevalence of AC and its implications for device
      programming. METHODS AND RESULTS: When AC occurred, the resulting QRS morphology
      was evaluated with the following pacing modes: (1) LV tip pacing plus RV AC, (2)
      Biventricular (BiV) pacing (i.e., both LV and RV tip pacing), and (3) BiV pacing
      plus RV AC. Several interventricular pacing (VV) intervals from 50 ms of LV
      preactivation to 30 ms of RV preactivation were tested in modes 2 and 3. From 38
      consecutive patients, AC was achieved in 14 (in 74% of the pacemakers and in none
      of the defibrillators). LV tip pacing plus RV AC obtained narrower QRS than BiV
      pacing at all VV intervals in seven of the patients with AC (50%). When BiV
      pacing is combined with RV AC, it produced a ventricular depolarization through
      two wave fronts (one from the LV tip and the second from either the ring or the
      tip of the RV lead depending on the VV interval programmed). CONCLUSIONS: AC
      obtained the narrowest QRS of all tested pacing modes in a significant proportion
      of patients undergoing CRT. Though the stimulus was delivered from three sites
      (BiV pacing plus RV AC mode), only two wave fronts of ventricular activation were
      seen by ECG.

PMID- 16981917
TI  - Long-term follow-up of patients supplied with single-chamber or dual-chamber
      cardioverter defibrillators.
AB  - INTRODUCTION: In patients who have an indication for an implantable cardioverter
      defibrillator (ICD) a dual-chamber device is indicated in the case of concomitant
      significant sinus node disease or atrioventricular block. It is a matter of
      debate whether dual-chamber ICD may be beneficial for patients with preserved
      sinus and atrioventricular nodal function as data from prospective randomized
      trials are limited. Mid- or long-term follow-up data are unavailable. METHODS AND
      RESULTS: One hundred patients (age 60+/-12 years, 11 women) with the indication
      for the implantation of an ICD and without antibradycardia pacing indication were
      randomly assigned to either receive a dual-chamber ICD (n=52) or a single-chamber
      ICD (n=48). Patients were followed-up for a mean of 52+/-14 months. Mortality and
      arrhythmogenic morbidity were assessed. All-cause mortality was 21% for single
      chamber and 31% for dual-chamber ICD recipients, respectively (P=0.26).
      Cardiovascular mortality was 13% for single-chamber ICD recipients versus 21% in
      the dual-chamber group (P=0.25). Subgroup analysis using 35% of ventricular paced
      beats as cutoff value in the dual-chamber ICD group revealed a 42% mortality rate
      for the patients with frequent ventricular pacing compared to 10% of patients
      with a low rate of ventricular pacing (P=0.05, relative risk 4.21, 95% confidence
      interval: 0.9-19.8). As for arrhythmogenic morbidity, the difference in the
      ventricular tachyarrhythmia load was not different in both groups (single
      chamber: 23+/-74 VT episodes, dual chamber: 54+/-134 VT episodes, P=0.17).
      CONCLUSION: In ICD recipients without conventional indication for dual-chamber
      pacing, dual chamber compared to single-chamber ICD has no advantage concerning
      mortality and arrhythmogenic morbidity in a long-term follow-up. In these
      patients the implantation of a single-chamber device is sufficient.

PMID- 16981918
TI  - Psychological reaction to potential malfunctioning of implantable defibrillators.
AB  - BACKGROUND: Psychological problems following implantable cardioverter
      defibrillators (ICD) implantation are diverse and include increased levels of
      anxiety. Anxiety may even rise further when possible malfunctioning of an ICD is
      announced, with a higher risk of serious ventricular arrhythmias and death as a
      consequence. Following the public statement of Medtronic, all patients in the
      Netherlands with the specific Medtronic ICD were contacted for extra device
      evaluation. The aim of this exploratory study was to determine whether the
      proportion of ICD patients with high levels of anxiety would increase after this
      extra device evaluation. METHODS: Patients were recruited from an ongoing
      prospective study on psychological effects of ICD implantation. Thirty-three
      patients completed the State subscale of the State-Trait Anxiety Inventory (STAI)
      before and after extra device evaluation. The STAI can identify patients with
      high levels of anxiety. RESULTS: A high level of anxiety was experienced by two
      patients (6.1%) at baseline and eight patients (24.2%) at follow-up (P=0.031).
      Hence, ICD patients were significantly more likely to experience high levels of
      anxiety following the public statement of potential malfunctioning of their
      device. CONCLUSION: A public statement regarding device safety may increase
      levels of anxiety among ICD patients. Given the potential triggering effect of
      high levels of anxiety on arrhythmias, psychological support may be considered
      for some of the ICD patients after such public statement.

PMID- 16981919
TI  - Mechanical esophageal deflection during ablation of atrial fibrillation.
AB  - To prevent esophageal damage during ablation of atrial fibrillation, we developed
      a technique to move the esophagus away from a desired ablation site too close to
      the esophagus. Under fluoroscopy, a transesophageal echocardiography probe was
      used to deflect the barium-opacified esophagus from the ablation site. This
      technique was successfully employed in three patients where critical sites of the
      posterior left atrial wall were very close to the esophagus.

PMID- 16981920
TI  - Pulmonary vein vestibule ablation for the control of atrial fibrillation in
      patients with impaired left ventricular function.
AB  - INTRODUCTION: Congestive heart failure (CHF) and atrial fibrillation (AF) are
      frequently linked, and when associated produce additive deleterious effects. In
      this prospective study, the effects of catheter ablation for AF in patients with
      impaired left ventricular (LV) function are presented. METHODS: Baseline data and
      clinical outcome have been prospectively collected in 105 consecutive patients
      who underwent pulmonary vein ablation for the control of AF. We evaluated 40
      patients affected by LV dysfunction with ejection fraction (EF)<40% and compared
      them to the remaining 65 patients with normal ventricular function in terms of
      changes in LV function, maintenance of sinus rhythm, and quality of life during
      follow-up. RESULTS: After a mean follow-up of 14+/-2 months, 87% of patients with
      impaired LV function and 92% of patients with normal ventricular function were in
      sinus rhythm, with or without antiarrhythmic therapy (P=NS). A significant
      improvement in LVEF and fractional shortening was documented in patients with CHF
      (33+/-2% vs 47+/-3%, and 19+/-4% vs 30+/-3%, P<0.01 for both comparisons).
      Evaluation of exercise capacity and quality of life documented better
      improvements in patients with CHF compared to patients without CHF. CONCLUSIONS:
      Catheter ablation in patients with LV dysfunction is feasible, not associated
      with higher procedural complications, and provides a significant improvement in
      LV performance, symptoms, and quality of life during follow-up.

PMID- 16981921
TI  - Nonfluoroscopic catheter navigation for radiofrequency catheter ablation of
      supraventricular tachycardia in children.
AB  - BACKGROUND: Radiofrequency catheter ablation (RCA) of supraventricular
      tachycardia (SVT) in children is highly successful but requires exposure to
      radiation. Nonfluoroscopic mapping systems may significantly reduce fluoroscopy
      time. METHODS: Forty consecutive pediatric patients who underwent RCA for
      accessory pathways (AP) or AV nodal reentrant tachycardia (AVNRT) with use of a
      nonfluoroscopic navigation system (Ensite NavX) (group A) were compared
      retrospectively to 40 consecutive patients with similar diagnoses who underwent
      RCA with fluoroscopic guidance only (group B). RESULTS: Group A (mean age 12.1+/
      2.9 years, mean weight 47+/-13.9 kg) consisted of 11 patients (27.7%) with AVNRT
      and 29 (72.5%) with AP. Group B (mean age 10.9+/-3.1 years, mean weight 47.1+/
      17.1 kg) consisted of 7 patients (17.5%) with AVNRT and 33 (82.5%) with AP. There
      were no significant differences in AP location, patients with congenital heart
      disease, and number of radiofrequency lesions. Fluoroscopy time was significantly
      shorter in group A than in group B (10.4+/-6.1, range 3.1-28.8 minutes, vs 24.9+/
      16.0, range 4.4-82.0 minutes, P<0.0001). Procedure duration was also
      significantly shorter in group A than in group B (170+/-68.5, range 90-420
      minutes, vs 218+/-69.3, range 90-360 minutes, P<0.0001). Initial success was 95%
      in group A and 100% in group B. Tachycardia recurrences occurred in two patients
      in group A (5%) and six patients in group B (15%). Final success, including
      repeat ablations for recurrences or failures, was 100% in both groups.
      CONCLUSIONS: The use of a nonfluoroscopic system for catheter navigation
      significantly reduced fluoroscopy exposure and total procedure duration of RCA of
      common SVT substrates in children.

PMID- 16981922
TI  - Incidence, time course, and characteristics of microbubble formation during
      radiofrequency ablation of pulmonary veins with an 8-mm ablation catheter.
AB  - BACKGROUND: Microbubble formation during pulmonary vein (PV) radiofrequency (RF)
      ablation of atrial fibrillation (AF) occurs relatively frequently. Prior studies
      have shown that microbubble formation may be associated with an increased risk of
      complications. However, the incidence, time course, and temperature
      characteristics of microbubble formation during AF ablation with an 8-mm catheter
      have not been prospectively described in humans. METHODS: We studied 46 (30 men,
      age 56+/-10 years) patients with AF who underwent RF ablation of PVs between
      January 2005 and December 2005 using an 8F, 8-mm Biosensetrade mark ablation
      catheter (Biosense-Webster, Diamond Bar, CA, USA). All patients underwent
      continuous intracardiac echocardiography (ICE). Microbubble patterns were
      classified as either type 1 (intermittent, scattered microbubble formation) or
      type 2 (explosive shower of dense microbubbles). Formation of any microbubbles
      was detected by ICE and the time, PV location, and electrode temperature were
      recorded. RESULT: A total of 1,479 (32+/-13, range 12-73) RF lesions were
      delivered to 167 veins. Twenty (2%) lesions were classified as type 2. Since the
      number of lesions resulting in type 2 bubbles was very small, only type 1 lesions
      were included in the final analysis. Thirty-nine (85%) patients had at least one
      lesion associated with bubble formation during ablation (mean: 7+/-7 lesions,
      range 1-28 lesions). Twenty-three percent (327) of the RF lesions resulted in
      bubble formation. RF generator power setting during lesions resulting in bubble
      formation was lower than lesions which did not result in bubble formation (47.9+/
      7.4 W vs 49.7+/-7.1 W, P<0.001). Logistic regression analysis revealed a
      significant negative correlation (P<0.001) between RF generator power settings
      and a positive correlation between the generator temperature settings and
      formation of bubbles (both P<0.02). However, the maximum temperature attained was
      not different between lesions resulting in bubble formation (n=327) and those
      which did not result in bubble formation (n=1,139). Fifty-three (16%) of the
      lesions associated with bubble formation occurred within 2-10 seconds after RF
      was begun. Bubble formation was significantly more frequent in left superior PVs
      compared to the other PVs (left superior PV 27.3% left inferior PV 18.6%, right
      superior PV 20.5%, and right inferior PV 18.8%, P=0.005, left superior PV vs
      other PVs, P<0.001) even after adjustment for the other factors including
      generator power settings and the temperature setting. CONCLUSION: Bubble
      formation is common during RF ablation of PV with 8-mm tip catheter and can occur
      as early as 2 seconds after starting RF. RF generator power is negatively
      correlated with bubble formation while generator temperature settings are
      positively correlated with formation of bubbles. Microbubble formation is also
      more frequent with ablation of the left superior PV probably due to better
      catheter contact in that area.

PMID- 16981923
TI  - Effect of right ventricular apex pacing on the Tei index and brain natriuretic
      peptide in patients with a dual-chamber pacemaker.
AB  - BACKGROUND: Asynchronous electrical activation induced by right ventricular apex
      (RVA) pacing can cause various abnormalities in left ventricular (LV) function,
      particularly in the context of severe LV dysfunction or structural heart disease.
      However, the effect of RVA pacing in patients with normal LV and right
      ventricular (RV) function has not been fully elucidated. The aim of this study
      was to characterize the effects of RVA pacing on LV and RV function by assessing
      isovolumic contraction time and isovolumic relaxation time divided by ejection
      time (Tei index) and by assessing changes in plasma brain natriuretic peptide
      (BNP). METHODS: Doppler echocardiographic study and BNP measurements were
      performed at follow-up (mean intervals from pacemaker implantation, 44+/-75
      months) in 76 patients with dual chamber pacemakers (sick sinus syndrome, n=30;
      atrioventricular block, n=46) without structural heart disease. Patients were
      classified based on frequency of RVA pacing, as determined by 24-hour ambulatory
      electrocardiogram (ECG) that was recorded just before echocardiographic study:
      pacing group, n=46 patients with RVA pacing>or=50% of the time, percentage of
      ventricular paced 100+/-2%; sensing group, n=30, patients with RVA pacing<50% of
      the time, percentage of ventricular paced 3+/-6%. RESULTS: There was no
      significant difference in mean heart rate derived from 24-hour ambulatory ECG
      recordings when comparing the two groups (66+/-11 bpm vs 69+/-8 bpm). LV Tei
      index was significantly higher in pacing group than in sensing group (0.67+/-0.17
      vs 0.45+/-0.09, P<0.0001), and the RV Tei index was significantly higher in
      pacing group than in sensing group (0.34+/-0.19 vs 0.25+/-0.09, P=0.011).
      Furthermore, BNP levels were significantly higher in pacing group than in sensing
      group (40+/-47 pg/mL vs 18+/-11 pg/mL, P=0.017). With the exception of LV
      diastolic dimension (49+/-5 mm vs 45+/-5 mm, P=0.012), there were no significant
      differences in other echocardiographic parameters, including left atrium (LA)
      diameter (35+/-8 mm vs 34+/-5 mm), LA volume (51+/-27 cm3 vs 40+/-21 cm3), LV
      systolic dimension (30+/-6 mm vs 29+/-7 mm), or ejection fraction (66+/-9% vs
      63+/-11%), when comparing the two groups. CONCLUSIONS: These findings suggest
      that the increase of LV and RV Tei index, LVDd, and BNP are highly correlated
      with the frequency of the RVA pacing in patients with dual chamber pacemakers.

PMID- 16981924
TI  - ICD shock triggered by atrial bigeminy.

PMID- 16981925
TI  - From gene therapy and stem cells to clinical electrophysiology.
AB  - Gene therapy, cell therapy, and tissue engineering are emerging as novel
      experimental therapeutic paradigms for a variety of cardiovascular disorders. In
      the current report we will review the possible implications of these emerging
      technologies in the field of cardiac electrophysiology. Initially, the possible
      role of myocardial gene and cell therapies in creating a biological alternative
      to electronic pacemakers for the treatment of bradyarrhythmias will be discussed.
      This will be followed by a description of the possible applications of using
      similar strategies for the treatment of common tachyarrhythmias. Finally, the
      electrophysiological implications of cardiac stem cell therapy for heart failure,
      as well as the possible in vitro applications of stem cell technology for
      electrophysiological studies and drug screening, will be discussed. While these
      emerging strategies provide a paradigm shift from conventional treatment
      modalities, this field is still at its infancy and several obstacles, discussed
      in this review, should be overcome before any clinical breakthroughs can be
      expected.

PMID- 16981926
TI  - The renin-angiotensin system: a therapeutic target in atrial fibrillation.
AB  - There is growing evidence to suggest a role for the renin-angiotensin system
      (RAS) in the pathogenesis of atrial fibrillation (AF). Experimental animal data
      suggest RAS-dependent mechanisms for the development of a structural and
      electrophysiologic substrate for AF. This is consistent with clinical data
      demonstrating the effectiveness of RAS blockade in preventing new-onset or
      recurrent AF in a variety of patient populations including patients with
      hypertension and left ventricular hypertrophy, congestive heart failure, and
      those undergoing electrical cardioversion for AF. This review summarizes
      experimental and clinical evidence to date relating to the role of RAS in the
      pathogenesis of AF, and the efficacy of its inhibition in managing this common
      arrhythmia.

PMID- 16981927
TI  - The homozygous KCNQ1 gene mutation associated with recessive Romano-Ward
      syndrome.
AB  - In a 7-year-old boy with normal hearing suffering from repeated syncope an
      extremely prolonged QTc interval (up to 700 ms) was found. The mother was
      completely asymptomatic and the father had an intermittently borderline QTc
      interval (maximum 470 ms) but no symptoms. In the proband a mutation analysis of
      KCNQ1 gene revealed a homozygous 1893insC mutation. The parents were heterozygous
      for this mutation. There was no consanguineous marriage in the family. The
      clinical relevance of these findings is that apparently normal individuals may
      have a latent reduction of repolarizing currents, a "reduced repolarization
      reserve," because they are carriers of latent ion channel genes mutations.

PMID- 16981928
TI  - Spontaneous polymorphic ventricular tachycardia after administration of
      pilsicainide in a patient resuscitated from ventricular fibrillation.
AB  - We performed a pilsicainide challenge test in a 38-year-old man who was
      resuscitated from ventricular fibrillation without apparent baseline
      electrocardiogram (ECG) abnormality. His father had a history of ventricular
      fibrillation and his brother had multiple episodes of syncope. Pilsicainide (1
      mg/kg) induced short coupled ventricular premature beats followed by repetitive
      polymorphic ventricular tachycardia without apparent J wave and ST elevation, and
      excessive changes in QRS duration and QT interval. An implantable cardioverter
      defibrillator was implanted.

PMID- 16981929
TI  - Electrocardiographic manifestations of cardiac metastasis in lung cancer.
AB  - We describe a case of primary lung cancer with myocardial metastasis, documented
      with electrocardiogram (ECG) mimicking myocardial ischemia and manifesting VT.
      Metastatic tumor to the myocardium proper is uncommon and difficult to diagnose
      because of nonspecific signs and symptoms. We observed such ECG changes in this
      case were initially misinterpreted as acute coronary syndrome. The diagnosis of
      cardiac metastasis was confirmed by contrast-enhanced magnetic resonance imaging
      and computed tomography.

PMID- 16981930
TI  - Ventricular fibrillation in a patient with prominent j wave in the inferior and
      lateral electrocardiographic leads after gastrostomy.
AB  - We describe the case of a 39-year-old man who experienced a ventricular
      fibrillation storm related to a prominent J wave in the inferior and lateral
      electrocardiographic leads on the day after gastrostomy. The J wave slowly
      decreased after amiodarone therapy (400 mg/day) was started, and ventricular
      fibrillation disappeared.

PMID- 16981931
TI  - Upgrading patients with chronic defibrillator leads to a biventricular system and
      reducing patient risk: contralateral LV lead placement.
AB  - Increasing numbers of patients with indwelling single- or dual- chamber internal
      cardioverter defibrillators (ICDs) will require upgrading of an existing system
      to a biventricular ICD providing cardiac resynchronization with back-up
      defibrillation. Upgrading, usually by the addition of a new left ventricular (LV)
      lead, can be technically challenging with central venous occlusion or stenosis
      often being the main obstacle to a successful procedure. We report a new
      technique of implanting a LV lead from the contralateral side to the existing ICD
      system to minimize the peri- and postoperative risk to the patient.

PMID- 16981932
TI  - Underestimation of pacing threshold as determined by an automatic ventricular
      threshold testing algorithm.
AB  - In this case report, we describe markedly different pacing thresholds determined
      by a manual threshold test and the automatic Ventricular Capture Management
      algorithm. The discrepancy in pacing threshold values reported was due to the
      difference in the AV intervals used with the different testing methods. We
      propose that the differences in right ventricular dimensions with altered
      diastolic filling periods affected the threshold in this patient with a new
      passive fixation lead in the right ventricular apex.

PMID- 16981934
TI  - Imaging of vascular disorders of the female pelvis.
AB  - Clinical presentation of vascular disorders of female pelvis including placental
      adhesion, retained product of conception, ovarian venous thrombosis, varices,
      torsion and haemorrhagic infarct of ovary is often non-specific. Because of its
      availability, safety, and cost-effectiveness, ultrasound is the first
      investigation of choice. Computed tomography and MRI clearly depict the pelvic
      and retroperitoneal anatomy. This pictorial essay illustrates the complementary
      role of US, CT, and MRI in diagnosing vascular disorders of female pelvis.

PMID- 16981935
TI  - Posttransplant lymphoproliferative disorder: a pictorial review.
AB  - Posttransplant lymphoproliferative disorder (PTLD) is a serious and potentially
      fatal complication after solid organ and haemopoietic stem cell transplantation.
      The frequency of PTLD varies with the type of organ transplant but overall it
      affects 2-10% of all solid organ transplant recipients. Most cases develop within
      1 year after the transplant, although occasional cases present 5-10 years later.
      Posttransplant lymphoproliferative disorder is clinically and pathologically
      heterogeneous - the majority are of the non-Hodgkin's lymphoma type, whereas
      Hodgkin's lymphoma arising after transplantation is rare. We have retrospectively
      reviewed patients with a histological diagnosis of PTLD after a solid organ
      transplant. We present the imaging features and a clinical review of this
      condition. Early diagnosis of PTLD may alter the management and outcome of the
      disease. The radiologist can play a vital role in establishing the diagnosis by
      imaging features supplemented with percutaneous biopsy and also in monitoring the
      disease response to treatment.

PMID- 16981936
TI  - Spontaneous intracranial hypotension: a study of six cases with MR findings and
      literature review.
AB  - Spontaneous intracranial hypotension is clinically characterized by orthostatic
      headache and other symptoms caused by low cerebrospinal fluid pressure due to
      leakage of cerebrospinal fluid from dural punctures or other medical causes. The
      other symptoms are mainly due to traction of the cranial and spinal nerves owing
      to descent of the brain caused by low cerebrospinal fluid pressure. Magnetic
      resonance imaging is very useful in the diagnosis because of its characteristic
      findings. We describe the MRI findings in six cases that had variable clinical
      presentation.

PMID- 16981937
TI  - Pulmonary embolism: accuracy and safety of a negative CT pulmonary angiogram and
      value of a negative D-dimer assay to exclude CT pulmonary angiogram-detectable
      pulmonary embolism.
AB  - This is a retrospective study to determine the accuracy and safety of a negative
      CT pulmonary angiogram (CTPA) based on clinical outcome and to determine the
      usefulness of a negative D-dimer assay before CTPA. A total of 483 patients with
      a negative CTPA study were followed up for 3 months, with the aim of detecting
      episodes of venous thromboembolism and mortality. Three hundred and forty-nine
      patients had an immunochromatographic D-dimer assay called 'Simplify', carried
      out before a CTPA examination. Seventy-eight patients had a negative D-dimer
      assay and a negative CTPA. Three patients had a negative D-dimer assay and a
      positive CTPA. All three patients had a moderate pretest clinical probability. Of
      the 483 patients who had a negative CTPA and a 3-month follow up, 444 (92%) were
      alive and 39 (8%) had died. Of the 444 patients who were alive, none had any
      further suspected episode of thromboembolism or had received anticoagulation
      therapy within the follow-up period. Of those who died, none of the deaths was
      thought to be as a result of pulmonary embolism (PE). Single-detector helical CT
      can be used safely as the primary diagnostic test to evaluate PE. Negative
      Simplify D-dimer assay and low pretest clinical probability exclude CTPA
      detectable PE, and a CTPA is unnecessary in this cohort of patients.

PMID- 16981938
TI  - Normal obstetric ultrasound reduces the risk of Down syndrome in fetuses of older
      mothers.
AB  - The objective of this study is to determine whether a normal fetal morphology
      ultrasound scan in women older than 35 years reduces the risk of aneuploidy. We
      reviewed the results of amniocentesis and second trimester sonogram in all women
      older than 35 years from 1991 to 1995. None had prior screening. We excluded
      fetuses with structural anomalies. We determined the sensitivity and specificity
      of minor markers in detecting Down syndrome and also determined the reduction in
      risk of a normal sonogram. Among the 2060 women older than 35 years giving birth
      during the study period, 16 (0.78%) delivered an infant with Down syndrome. Of
      the 16 fetuses, two had no prenatal testing or ultrasound, two had invasive
      testing but no second trimester sonogram, five had a normal sonogram and seven
      had one or more sonographic markers of Down syndrome. At least 17% of women older
      than 35 years did not participate in prenatal testing or ultrasound. Ultrasound
      detected Down syndrome with a sensitivity of 59% (95% confidence interval: 45
      72%), a false-positive rate of 10.6% (9.4-11.8%) and a positive predictor value
      of 1 in 9. The likelihood of having normal karyotype if the sonogram was normal
      was 0.46 (0.31-0.61). In women older than 35 years, a normal second trimester
      sonogram reduces the risk of Down syndrome by more than 50%. At least 17% of
      women older than 35 years do not participate in prenatal testing or ultrasound.

PMID- 16981939
TI  - Duration of pneumothorax as a complication of CT-guided lung biopsy.
AB  - The purpose of this study was to determine management guidelines for biopsy
      induced pneumothorax with the assistance of manual aspiration, mainly based on
      the duration of complicated pneumothorax. Data from 388 consecutive percutaneous
      needle lung biopsies were examined. Patients with pneumothorax on postbiopsy
      chest CT images underwent percutaneous manual aspiration with an 18-G i.v.
      catheter. Frequency and management of biopsy-induced pneumothorax and period to
      its disappearance were reviewed. Postbiopsy pneumothorax occurred in 133 of 388
      (34.3%) procedures. Manual aspiration in 72 of these 133 patients was carried out
      immediately after biopsy. The pneumothorax had resolved completely on follow-up
      chest radiographs without chest tube placement in 121 of the 133 pneumothoraces
      (91.0%). In cases requiring chest tube, the mean period from biopsy until
      resolution of the pneumothorax was 6.0 +/- 5.3 days, but was only 2.4 +/- 2.9
      days when chest tube placement was not needed. Specifically, time until recovery
      was short both in those not requiring manual aspiration (2.1 +/- 3.4 days) and in
      those with a pneumothorax that disappeared completely or almost completely after
      manual aspiration (1.9 +/- 2.0 days). The almost equally short recovery periods
      in patients not requiring manual aspiration and those requiring immediate manual
      aspiration indicates the value of rapid management.

PMID- 16981940
TI  - Radiology curriculum for medical students: clinicians' perspectives.
AB  - This study was conducted to establish clinicians' perspectives of a set of
      radiology curriculum topics for medical student teaching, which were held to be
      important by radiologists. A questionnaire was sent to clinicians in all
      specialties. Forty-six clinicians (51.1%) out of 90 returned the questionnaires.
      All curriculum topics were scored above an average of 4 (agree). The five highest
      ranking curriculum topics in order of importance were: developing a system for
      viewing chest radiographs (5.59), developing a system for viewing abdominal
      radiographs (5.56), developing a system for viewing bone and joint radiographs
      (5.33), distinguishing normal structures from abnormal in chest and abdominal
      radiographs (5.33) and identifying gross bone or joint abnormalities in skeletal
      radiographs (5.22). Correlative analysis between speciality groups showed
      surgical and medical specialities were significantly different in their responses
      of two learning outcomes: basic knowledge about the contrast media benefits and
      risks (P= 0.01) and ability to select the most appropriate and the most cost
      effective methods of radiological investigations for clinical situations (P=
      0.03). Acute specialities were not significantly different from the other two
      groups for these two learning outcomes. There was no statistically significant
      difference for other learning outcomes between the three speciality groups.

PMID- 16981941
TI  - Alternative technique for transjugular intrahepatic portosystemic shunt in a
      young child.
AB  - Liver transplantation is safer, more readily available and is increasingly being
      carried out in younger patients. Therapeutic bridging procedures such as
      transjugular intrahepatic portosystemic shunt have therefore become more relevant
      to paediatrics, especially in the group of patients who are too unstable for
      surgery or in whom a liver graft is not available. We describe a transjugular
      intrahepatic portosystemic shunt procedure in a 4-year-old child with life
      threatening variceal bleeding in whom the conventional procedure had failed. This
      technique may provide an alternative to conventional transjugular intrahepatic
      portosystemic shunt in this group.

PMID- 16981942
TI  - Peripherally inserted central catheters and upper extremity deep vein thrombosis.
AB  - The purpose of the study was to determine the incidence and risk factors for
      venous thrombosis in patients with a peripherally inserted central catheter
      (PICC). A retrospective study of all upper extremity venous duplex scans was
      carried out in the Vascular Medicine department from year 2000 to 2002 inclusive.
      A chart review of positive scans was undertaken to identify possible thrombotic
      risk factors. Of 317 upper extremity venous duplex scans carried out, 115, or
      32%, were positive for upper extremity deep vein thrombosis. Three main risk
      factors were identified - presence of a central line, malignancy and
      administration of chemotherapy. PICC were the most common central line present.
      Symptomatic thrombosis occurred in 7% of PICC inserted for chemotherapy compared
      with 1% of PICC inserted for other reasons. Ten per cent of the patients
      receiving chemotherapy through a PICC developed a thrombosis. The post-thrombotic
      syndrome was infrequent following upper extremity deep vein thrombosis. Patients
      receiving chemotherapy through a PICC are at increased risk of thrombosis. There
      may be a role for prophylactic low-dose anticoagulation in these high-risk
      patients.

PMID- 16981943
TI  - Patient satisfaction in radiation oncology.
AB  - As part of a quality improvement exercise at the Perth Radiation Oncology Centre,
      a survey was undertaken to ascertain the current level of patient satisfaction
      with the information they were receiving from their treating radiation
      oncologist. In addition, the effect of radiation on patients' anxiety levels was
      investigated. Two questionnaires were given to patients having radical
      radiotherapy for malignancy. The first questionnaire consisted of the Information
      Satisfaction Questionnaire and the State Trait Anxiety Index. It was given to
      patients before the commencement of their course of radiotherapy. The second
      questionnaire consisted of the State Trait Anxiety Index and was given at the
      completion of their radiotherapy. A total of 120 patients completed both the
      questionnaires. The majority of patients were satisfied/very satisfied with the
      explanation of their illness and radiation toxicities. Fewer patients were
      satisfied with the explanation of lifestyle (e.g. diet, exercise, smoking) and
      practical issues such as parking and treatment costs. The patients showed a
      statistically significant reduction in both their State and Trait Anxiety scores
      following radiotherapy. Following this study, we have developed new information
      booklets addressing lifestyle and practical issues, which were not being
      adequately addressed as shown in this study. Our next study will assess the
      effect of these new information booklets.

PMID- 16981944
TI  - Comparison of non-coplanar and coplanar irradiation techniques to treat cancer of
      the pancreas.
AB  - We compared two different techniques of pancreatic irradiation using measures
      associated with normal tissue complications. Seven consecutive patients with
      pancreatic cancer were planned for both coplanar and non-coplanar (NCP) external
      beam radiation treatments, using the same defined anatomical volumes for each
      patient, in each case. Each pair of plans was then compared using a range of
      objective criteria. Individual normal tissues were assessed against traditional
      tolerance limits. Selected dose-points, normal tissue complication probability
      (NTCP) and equivalent uniform doses (EUD) were also compared, as were indices
      combining information from individual tissues - total NTCP and total weighted
      EUD. All individual normal tissues doses were within established tolerance
      limits. For NCP relative to coplanar planning, NTCP and EUD were lower for all
      individual tissues in four cases and one case, respectively, i.e. in most cases a
      benefit to one tissue was offset by detriment to others. Summary measures
      demonstrated overall benefits for NCP techniques, with the total NTCP in six
      patients, and with the total weighted EUD in all patients. NCP techniques show
      potentially useful benefits. We present a new objective measure, the total
      weighted EUD, which may be particularly useful comparing plans where there are
      multiple critical tissues.

PMID- 16981945
TI  - Use of topical misoprostol to reduce radiation-induced mucositis: results of a
      randomized, double-blind, placebo-controlled trial.
AB  - Radiation-induced mucositis is an acute reaction of the mucosa of patients
      undergoing head and neck radiotherapy. It can have debilitating and dose-limiting
      consequences. There is no consensus on an accepted intervention that
      significantly reduces its severity. Misoprostol is a synthetic prostaglandin E1
      analogue, with properties of a mucosal cytoprotectant. We designed a randomized,
      double-blind, placebo-controlled trial of misoprostol in patients with head and
      neck cancer. The aim of this study was to determine if topical misoprostol was
      effective in reducing the severity of radiation-induced mucositis in patients
      receiving radical dose radiotherapy. The effect of this intervention on a
      patient's general well-being was also investigated. The primary end-point of the
      study was the incidence of Radiation Therapy Oncology Group grade 3 mucositis.
      Between 1999 and 2002, 83 patients were recruited into the study at Westmead and
      Nepean Hospitals, Sydney. Forty-two patients were randomized to receive
      misoprostol and 41 to receive a placebo. Most patients received radiotherapy in
      the adjuvant setting (52 of the 83) and had either an oral cavity (42 of the 83)
      or an oropharyngeal (16 of the 83) cancer. We could not identify any significant
      difference in the incidence of severe mucositis based on whether patients were
      allocated to receive misoprostol or placebo. There was no significant difference
      in the mean area under the mucositis curve (13.2 vs 16.6; P = 0.1). Patients
      allocated to misoprostol did report slightly increased soreness (7.6 vs 6.9; P =
      0.04) and a greater use of analgesics. However, this difference did not translate
      into a worse feeling of general well-being as measured by a simple visual
      analogue scale (5.8 vs 5.2; P = 0.3). In conclusion, we were unable to identify a
      reduction in radiation-induced mucositis in patients receiving misoprostol. There
      is a paucity of high-level evidence on potentially useful interventions and a
      continued need for new and innovative research, incorporating quality-of-life
      measurements, in patients experiencing radiation-induced mucositis.

PMID- 16981946
TI  - Outcome of post-prostatectomy radiotherapy in one institution.
AB  - We present a retrospective study to evaluate the outcome of postoperative
      radiotherapy for biochemical or clinical recurrent prostate cancer. Twenty-six
      patients (median age 60 years) underwent radiotherapy after radical prostatectomy
      between January 1997 and January 2004. Seven patients received adjuvant
      radiotherapy and 19 received salvage radiotherapy. The median prostate-specific
      antigen at diagnosis was 8.6 (0.9-89) and most (23 patients) presented with
      T(3)N(0) disease. The median follow up was 19.5 months (5-84 months). All
      patients received a dose of 61.2 Gy at 1.8 Gy per fraction, 20 initially
      receiving 45 Gy to the lesser pelvis. The median dose to the bladder, rectum and
      left femoral head were 55.6, 57.5 and 33.8 Gy, respectively. All patients were
      managed radiotherapeutically by the first author. Twenty-four patients are alive.
      Two patients have died, one from oesophageal cancer and the second from
      metastatic prostate cancer. Two other patients also developed metastatic disease.
      Four asymptomatic patients with a rising prostate-specific antigen are under
      observation. None of the 26 patients has developed a local recurrence. Seven
      patients have developed grade 1 late bowel effects and three a grade 2 late
      effect. Eight patients suffer from grade 1 late genitourinary effects and two
      from grade 2 effects. One patient developed impotence, whereas 23 patients were
      rendered impotent postoperatively. There were no grade 3/4 late effects.
      Postoperative radiotherapy is well tolerated and provides effective local
      control.

PMID- 16981947
TI  - Metastatic choriocarcinoma: a rare cause of stroke in the young adult.
AB  - A 20-year old woman presented with acute right hemiplegia 10 weeks after
      intrauterine fetal death at 34-weeks gestation (G1P0). A brain MRI showed a
      typical acute infarct in the left middle cerebral artery territory. A CT
      pulmonary angiography carried out 1 week later for sudden cardiopulmonary
      deterioration showed disseminated pulmonary metastases. The CT was extended to
      the abdomen and pelvis, which showed a uterine mass with bilateral theca lutein
      cysts. The radiological diagnosis of metastatic choriocarcinoma was made and was
      subsequently confirmed with the markedly increased serum beta-human chorionic
      gonadotrophin. A serum beta-human chorionic gonadotrophin is therefore considered
      worthwhile in any young female adult who presents with stroke.

PMID- 16981948
TI  - Cholecystocolonic fistula diagnosed with CT-intravenous cholangiography.
AB  - Cholecystoenteric fistulas are often not diagnosed preoperatively and delineation
      of fistula can have an influence on surgical planning. We report a case of
      cholecystocolonic fistula diagnosed preoperatively using CT-i.v. cholangiography
      and review the published reports.

PMID- 16981949
TI  - Bilateral lipoma arborescens of the subdeltoid bursa.
AB  - Lipoma arborescens is a rare cause of chronic monoarticular arthritis. It is most
      commonly seen in the knees, but only a few cases involving other joints,
      especially the subdeltoid bursa, have been described. To our knowledge, this is
      the first reported case of lipoma arborescens involving bilateral subdeltoid
      bursae. Although it is associated with joint effusion, synovial cysts and
      erosions, the presence of reactive bone formation has not been reported. Magnetic
      resonance imaging is a very effective method for the diagnosis of this rare
      condition because of its ability to do tissue characterization.

PMID- 16981950
TI  - Echocardiogram-gated multislice spiral CT in functionally univentricular heart
      following long-lasting Waterston-Cooley anastomosis.
AB  - Waterston-Cooley anastomosis may be carried out in patients with tricuspid
      atresia to provide pulmonary perfusion. It is associated with several
      complications, including preferential blood flow to the right lung, hypoplasia of
      the left pulmonary artery, obstruction of the anatomosis or rupture of pulmonary
      aneurysms. We study a patient with thrombosis in the pulmonary arteries following
      surgical construction of a Waterston shunt in childhood. Imaging findings and
      clinical symptoms are discussed with emphasis on echocardiogram-gated multislice
      spiral CT.

PMID- 16981951
TI  - Non-cavernomatous superior mesenteric thrombosis successfully recanalized with
      interventional radiological procedures carried out with a combination
      transmesenteric and transjugular approaches.
AB  - This is the study of a 52-year-old man with oesophageal, rectal and anal varices
      caused by portal hypertension with complete obstruction of the superior
      mesenteric vein. Treatment by two sessions of interventional radiological
      procedures was successful. The first was a catheter-directed thrombolysis using
      the transmesenteric approach. The second was percutaneous transluminal
      angioplasty and stent implantation for the obstructed segment of the superior
      mesenteric vein and the creation of a transjugular intrahepatic portosystemic
      shunt. In the second session, devices were advanced over a guidewire inserted
      from the right jugular vein and pulled out of the ileocolic vein using the pull
      through technique.

PMID- 16981952
TI  - Leiomyosarcoma of the great saphenous vein.
AB  - Peripheral vascular leiomyosarcomas are rare. A case of leiomyosarcoma of the
      great saphenous vein diagnosed pre-surgically by MRI and fine-needle aspiration
      is presented. Characteristics of the tumour and imaging features are discussed.

PMID- 16981953
TI  - Ovarian vascular pedicle sign in ovarian metastasis arising from gall bladder
      carcinoma.
AB  - A case of a large mass in the pelvis confirmed to be a rare ovarian metastasis
      arising from a primary adenocarcinoma of the gall bladder is presented. The value
      of the recently described ovarian pedicle sign in confirming the organ of origin
      of the pelvic mass is emphasized.

PMID- 16981957
TI  - Conflict of interest: Full disclosure is essential.

PMID- 16981958
TI  - The sad, misunderstood prostate: Understanding perceptions and reality.

PMID- 16981954
TI  - Laparoscopic scar: a mimicker of Sister Mary Joseph's nodule on positron emission
      tomography/CT.
AB  - Positron emission tomography/CT is an established imaging method in the diagnosis
      and staging of cancers. (18)F-fluoro-2-deoxy-d-glucose (FDG) is the most commonly
      used radiotracer in positron emission tomography/CT. It is a tumour viability
      agent and usually its uptake within a lesion reflects the presence of a viable
      tumour tissue. However, false-positive FDG uptake is known to occur in benign
      processes of either inflammatory or infectious aetiology. We describe FDG uptake
      at the site of laparoscopic scar that mimicked Sister Mary Joseph's nodule in a
      patient with gastric adenocarcinoma. Here, the knowledge of the patient's history
      and subtle imaging findings helped in accurate staging of the patient. In this
      case report, we emphasize the value of the knowledge of the patient history and
      awareness of different pitfalls of FDG to achieve a correct diagnosis on positron
      emission tomography/CT.

PMID- 16981959
TI  - Low HDL-cholesterol: Common and under-treated, but which drug to use?

PMID- 16981960
TI  - Erectile dysfunction in diabetes: 'NO' role for the endothelium?

PMID- 16981961
TI  - The rising tide of aggression and delinquency in adolescent girls.

PMID- 16981962
TI  - Magnetic resonance imaging to evaluate NASHA/Dx gel (Zuidex) for stress urinary
      incontinence.
AB  - The Zuidex system for the treatment of stress urinary incontinence consists of
      non-animal stabilised hyaluronic acid/dextranomer (NASHA/Dx) gel and a precision
      guide, the Implacer. Whether the Implacer accurately deposits NASHA/Dx gel in the
      desired location within the urethral wall was investigated by magnetic resonance
      imaging (MRI), performed at a mean of 35 days post-treatment. Three or more
      deposits were observed in 11 of 16 patients (68.8%), with 39 of the 50 deposits
      clearly located within the urethral wall, as intended. Fourteen of 16 patients
      (87.5%) demonstrated improvement in their incontinence at 3 months, sustained at
      12 months in 13 patients. No significant correlations between total implant
      volume and improvements in incontinence were observed at 3 months (p > or = 0.16)
      and 12 months (p > or = 0.30). In conclusion, accurate placement of NASHA/Dx gel
      into the desired location within the urethral wall was achieved in the majority
      of cases using the Implacer device, without endoscopic guidance.

PMID- 16981963
TI  - DNA damage in metabolic syndrome and its association with antioxidative and
      oxidative measurements.
AB  - The purpose of this study was to assess DNA damage levels in subjects with
      metabolic syndrome (MetS). Sixty-five subjects with MetS and 65 controls were
      enrolled in this study. Levels of DNA damage, total antioxidant capacity (TAC),
      total peroxide and oxidative stress index (OSI) were measured. We found that DNA
      damage levels were significantly increased [155.5 (60-264) vs. 93.2 (0-208)
      arbitrary units; p < 0.001] and TAC levels were significantly decreased in MetS
      than in control (1.34 +/- 0.27 vs. 55 +/- 0.33 mmol Trolox equivalent/l; p <
      0.001). A significant falling trend in TAC levels and a significant rising trend
      in DNA damage values with the increase in the number of metabolic disturbances
      (anova p < 0.001 for both) were observed. Total peroxide (30.9 +/- 4.9 vs. 21.3
      +/- 2.5 micromol H2O2/l; p < 0.001) and OSI levels [2.4 (1.3-3.8) vs. 1.4 (0.7
      2.3) arbitrary units; p < 0.001] were significantly higher in the subjects with
      MetS than in controls. We found significant negative correlation between DNA
      damage and TAC levels in MetS (r = -0.656, p < 0.001) and in control (r = -0.546,
      p < 0.001). In multiple linear regression analysis, age, body mass index,
      presence of MetS and number of the components of MetS were independent predictors
      of log-transformed DNA damage (p < 0.05, for all). DNA damage is increased in
      patients with MetS. The increase in DNA damage might be occur because of the
      increase in the imbalance between the production of oxidants and antioxidant
      defences in subjects with MetS.

PMID- 16981964
TI  - Renal functional reserve in obesity hypertension.
AB  - The capacity to increase glomerular filtration rate in response to an acute oral
      protein load is known as the renal functional reserve; the loss of such capacity
      is used as a marker of hyperfiltration. This physiological response in obese
      hypertensives is not yet fully understood. We aimed to study the interdependent
      effects of obesity and hypertension on renal reserve, taking into account renal
      kallikrein and nitric oxide in the modulation of that parameter. Fourteen obese
      hypertensives (mean age, 50.5 +/- 0.9 years) and nine lean hypertensives (mean
      age, 50.6 +/- 2.7 years) were evaluated. Renal haemodynamics and the levels of
      serum nitric oxide and urinary kallikrein were assessed at baseline and after a
      protein load (1 g/kg of body weight). An increase in the following parameters was
      observed when comparing obese and lean hypertensives: basal glomerular filtration
      rate; renal plasma flow; and urinary kallikrein and nitric oxide levels (129.2 +/
      2.9 vs. 101.4 +/- 3.4 ml/min/1.73 m2; 587.5 +/- 18.2 vs. 502.8 +/- 16.7
      ml/min/1.73 m2; 0.120 +/- 0.02 vs. 0.113 +/- 0.02 mU/ml; 23.2 +/- 0.8 vs. 19.5 +/
      1.2 mmol/ml, respectively). The renal reserve was lower in obese hypertensives
      when compared with that of lean hypertensives (4.1 +/- 0.5 vs. 11.8 +/- 0.8
      ml/min, p < 0.005). After a protein load, contrasting with the lean group,
      inability to elevate the nitric oxide serum levels and a lower increase in
      urinary kallikrein were observed in the obese group. These data suggest that
      obese hypertensives lose renal reserve earlier in the evolution to renal
      dysfunction. This may be due to the defective modulation of renal vasodilatation
      mechanisms by renal kallikrein and nitric oxide production.

PMID- 16981965
TI  - Staphylococcus aureus nasal carriage among the diabetic and non-diabetic
      haemodialysis patients.
AB  - Staphylococcus aureus is the most common cause of serious infections in patients
      undergoing long-term haemodialysis (HD). S. aureus infections in HD patients are
      associated with considerable morbidity and mortality. Especially, methicillin
      resistant S. aureus (MRSA) strains are becoming increasingly multidrug-resistant
      and have recently developed resistance to vancomycin, used successfully to treat
      MRSA for more than 30 years. In vitro determination of resistance patterns of S.
      aureus is critical in terms of administering suitable antimicrobial treatment.
      The objective of this study was to identify the frequency of S. aureus among
      diabetic and non-diabetic HD patients and to investigate resistance patterns
      against various antibiotics used broadly for treatment. This study was carried
      out between January 2004 and December 2004. In the present survey, 261 patients
      undergoing HD treatment from three HD units in Hatay were examined. A total of
      148 Staphylococcus aureus strains were processed to assess their occurrence rates
      and antimicrobial susceptibility profiles. S. aureus positivity was determined in
      148 (56.7%) of the 261 HD patients and 26 (16.2%) of the 160 individuals in the
      control group. The difference was significant (p < 0.001). HD length was found to
      be 38.4 +/- 24.3 months in the patients of S. aureus carrier and 27.3 +/- 18.5
      months in non-carrier patients. Significant correlation was also identified
      between durations those on HD and the isolation of S. aureus (p < 0.001).
      However, the carrier state was unrelated to the presence of diabetes mellitus
      (DM), age or sex. In conclusion, nasal carriage of S. aureus was found to be more
      prevalent in HD patients than that in those in the control group. Also, it is
      concluded that DM was not a risk factor for the nasal carriage of S. aureus. In
      addition, the rates of antibiotic resistance of S. aureus strains were found to
      be quite higher in HD patients than in the control group (p < 0.05).

PMID- 16981966
TI  - Fluticasone propionate/salmeterol hydrofluoroalkane via metered-dose inhaler with
      integrated dose counter: Performance and patient satisfaction.
AB  - Currently, patients have to keep track of doses to determine when to replace
      their metered-dose inhalers (MDIs). This study evaluated the performance and
      patient satisfaction of a novel MDI with an integrated dose counter. In an open
      label study at 38 outpatient centres, patients > or =12 years old with asthma or
      chronic obstructive pulmonary disease (COPD) received two actuations of
      fluticasone propionate/salmeterol 125/25 microg (115/21 microg ex-actuator)
      hydrofluoroalkane (ADVAIR) HFA) via MDI with counter twice a day until all 120
      actuations were completed. Concordance between counter and diary recordings in
      patients who reported use of > or =90% of labelled actuations (completer
      population, n = 228) was high (discrepancy rate of 0.94%) and the incidence of
      device firing without changes in counter readings was low (0.13%). Mean expected
      actuations based on canister weights (114) were slightly lower than mean counter
      (121) and diary reported actuations (120). Upon study completion, 95% of patients
      were satisfied with the dose counter and 92% agreed it would help prevent them
      from running out of medication. Safety assessments (intent-to-treat population, n
      = 237) indicated that the drug was well tolerated. This integrated MDI counter
      may help patients maintain better disease control by enabling them to accurately
      track their medication supply.

PMID- 16981967
TI  - Once-daily vs. twice-daily intrapleural urokinase treatment of complicated
      parapneumonic effusion in paediatric patients: A randomised, prospective study.
AB  - To evaluate the effective dose frequency (once daily vs. twice daily) of
      intrapleural urokinase treatment in children who required tube thoracostomy for
      drainage of a complicated parapneumonic effusion, we designed a randomised
      prospective study in a tertiary medical centre in Taiwan. From June 2002 to
      January 2005, 30 paediatric patients with complicated parapneumonic effusion who
      had received chest tube drainage were randomised 1 : 1 to the once-daily
      (urokinase 5000-6000 IU/kg/dose) or twice-daily (urokinase 2500-3000 IU/kg/dose)
      treatment. We compared clinical manifestations and outcomes in both groups. There
      were no differences in pleural effusion characteristics between the groups. Six
      patients had Streptococcus pneumoniae, one had Staphylococcus aureus, one had
      Group A Streptococcus, and 22 had unknown pathogens. There were no significant
      differences between the once- vs. twice-daily group in the amount of drained
      pleural fluid (564.9 +/- 422.1 ml vs. 560.5 +/- 198.6 ml, respectively), fever
      duration after chest tube insertion (4.3 +/- 3.2 days vs. 5.3 +/- 2.7 days), or
      total admission days (14.3 +/- 3.9 days vs. 14.6 +/- 3.0 days) (p > 0.05 for
      all). Only two patients (one in each group) required the surgery. Thus, we found
      that both once- and twice-daily administration of urokinase were similarly
      efficacious, and resulted in good clinical outcomes. Both obviated the need for
      surgery in most (93%) cases of pneumonia with complicated parapneumonic effusion
      in this series. A larger, multicentre study is necessary to verify our findings.

PMID- 16981968
TI  - Neural network technology to predict intracellular water volume.
AB  - Artificial neural network (ANN) is increasingly applied in clinical medicine. We
      therefore constructed an ANN to predict intracellular water (ICW) volume in 44
      healthy Taiwaners. Demographic and anthropometric data were recorded as
      predictors, and ICW volume measured by bioelectrical impedance analysis (ICW-BIA)
      was the reference. ICW volume predicted by ANN (ICW-ANN) was compared with ICW
      BIA. ICW-BIA (21.26 +/- 0.58 l) and ICW-ANN (21.25 +/- 0.57 l) was
      insignificantly different (p = 0.76). ICW-BIA and ICW-ANN were strongly
      correlated (r = 0.94, p < 0.0001) with a significant agreement (mean difference,
      0.01; lower and upper limits of agreement, -2.31 and 2.33) in Bland-Altman plot.
      Passing-Bablok regression was described as ICW-BIA = 1.04 x ICW-ANN - 0.49, with
      95% confidence interval for slope 0.94-1.14 and for intercept -2.76-1.49,
      indicating that both methods were interchangeable. ANN provided an excellent
      alternative of BIA to predict ICW volume in healthy subjects.

PMID- 16981969
TI  - Thromboprophylaxis in ENT patients: A national survey.
AB  - The aim of this survey was to establish whether ENT departments in England follow
      British Medical Journal guidelines on thromboprophylaxis. A telephone survey of
      doctors in 80 ENT departments was used to present six clinical scenarios. The
      participants were asked what their local department routinely did. They were also
      asked whether they were aware of a local or national thromboprophylaxis policy.
      For patients undergoing procedures other than major head and neck procedures,
      compliance was poor and ranged between 7.5% and 37.5%. For laryngectomy, the rate
      was 82.6%. There was no statistical difference in answers given by doctors of
      different levels of seniority. Where local thromboprophylaxis guidelines exist,
      compliance is found to be statistically better. These results suggest that most
      ENT departments do not follow national or local guidelines on thromboprophylaxis.
      Greater awareness of existing guidelines is required.

PMID- 16981970
TI  - Overactive bladder: The importance of new guidance.
AB  - Overactive bladder (OAB) affects an estimated 49 million people in Europe, but
      only a minority receive appropriate treatment. Others are bothered by
      unacceptable levels of symptoms that severely impair their quality of life and
      represent a significant financial burden to themselves and to their healthcare
      providers. Recently updated guidelines from the International Consultation on
      Incontinence (ICI) and the European Association of Urology (EAU) take account of
      important new developments in the management of bladder problems in both primary
      and secondary care. However, local implementation of previous guidance has been
      variable, with many patients with OAB and other bladder problems failing to gain
      full benefit from current clinical and scientific understanding of these
      conditions. The recent expansion of the range of treatments available for OAB and
      stress urinary incontinence makes it especially important that physicians become
      aware of the differential diagnosis of these conditions - the questions they need
      to ask, and the investigations which will help determine the most appropriate
      course of action.

PMID- 16981971
TI  - Thiazolidinediones, insulin resistance and obesity: Finding a balance.
AB  - The clinical efficacy of currently available thiazolidinediones (TZDs) in
      improving glycaemic control and ameliorating several risk factors for
      cardiovascular disease (linked to their insulin-sensitising actions as well as
      direct vascular effects) is well established. Treatment-associated weight gain,
      however, which has been identified as a class effect of the TZDs, is seen in a
      number of patients. The magnitude of weight gain correlates in part with improved
      metabolic control, i.e. better responders are more prone to increases in body
      weight. The cardiovascular risk associated with obesity appears to be depot
      specific; while peripheral obesity is associated with a low risk of
      cardiovascular complications, central obesity confers a greater degree of risk.
      Evidence is reviewed that increases in body weight associated with TZD treatment
      are associated with neutral effects (or even, decreases) in visceral fat, the
      adipose depot that is associated with central obesity.

PMID- 16981972
TI  - Basic concepts in meta-analysis: A primer for clinicians.
AB  - With the expanding volume of medical literature, meta-analysis, a form of
      systematic review, has become indispensable for clinicians for evidence-based
      decision making. While the number of meta-analyses has substantially increased
      during recent years, there are still controversial issues regarding their
      methodology, interpretation and clinical application. In this review, the basic
      concepts of meta-analysis have been discussed from a clinician's perspective in
      order to facilitate its understanding, appraising and applicability in clinical
      practice. Although randomised controlled trials are the usual source for meta
      analysis, observational studies are also being increasingly considered for meta
      analysis. Like every other research design, meta-analysis starts with formulating
      a question, followed by searching for related data, based on predefined criteria
      and strategies. Inclusion of studies must be carried out with careful
      consideration of their quality and assessment of homogeneity using graphical
      means as well as statistical tools such as Q statistics, I(2) statistics and meta
      regression. The pooled effect size is commonly calculated using either a 'fixed
      effect model' or 'random effect model'. Publication bias and other source of bias
      should be investigated and the impact of potential confounders should be
      eliminated as required. Given the above-mentioned considerations, meta-analysis
      can provide a more precise estimate of an effect size to be used in clinical
      decision making.

PMID- 16981973
TI  - Novel anti-hepatitis B agents: A focus on telbivudine.
AB  - Although preventable by vaccination, hepatitis B infection is common, affecting
      more than 350 million individuals worldwide. Chronic hepatitis B infection is
      associated with the complications of chronic liver disease including cirrhosis
      and hepatocellular carcinoma. Current agents designed to target hepatitis B are
      hindered by the development of resistance, poor tolerability or limited efficacy
      and a demand for new agents and strategies continues. This review focuses on
      telbivudine, a novel agent in the fight against hepatitis B.

PMID- 16981974
TI  - Acute pseudo-obstruction of the colon (Ogilvie's syndrome) following instrumental
      vaginal delivery.
AB  - Acute pseudo-obstruction of the colon (Ogilvie's syndrome) is an adynamic ileus
      without mechanical obstruction of the bowel. Predisposing factors include:
      abdominal and pelvic surgery, or trauma, or severe pre-existing systemic illness.
      In obstetrics, many cases have been reported after caesarean delivery, but none
      following a vaginal delivery. Conservative and pharmacological therapies are
      effective in many patients, but surgical intervention may be required. Early
      diagnosis and appropriate treatment is imperative to avoid caecal rupture, faecal
      peritonitis and the associated high maternal mortality. High index of clinical
      suspicion and proper assessment of the gastrointestinal system in the post
      surgical patient are vital to the management of this uncommon but potentially
      serious condition met with in obstetrics practice.

PMID- 16981975
TI  - A case of progressive pseudorheumatoid arthropathy of 'childhood' with the
      diagnosis delayed to the fifth decade.
AB  - Progressive pseudorheumatoid arthropathy of childhood (PPAC) is a rare single
      gene disorder which is frequently misdiagnosed as juvenile rheumatoid arthritis.
      It is characterised with arthralgia, joint contractures, bony swelling of
      metacarpophalangeal and interphalangeal joints and platyspondyly. Clinical and
      laboratory signs of joint inflammation such as synovitis, a high erythrocyte
      sedimentation rate and an elevated C-reactive protein level are usually absent.
      Although the disease begins early in life (usually between 3 and 8 years of age),
      the diagnosis may be delayed. In the present case report, we describe a male
      patient diagnosed with PPAC at the age of 46 years, although he had been
      exhibiting the typical radiological and clinical features of the disease since
      the age of 7 years.

PMID- 16981976
TI  - Paraneoplastic syndrome, infection or arthritis: Difficulties in diagnosis.
AB  - Many different diseases have overlapping clinical symptoms. A major challenge in
      daily clinical practice is to differentiate between diseases associated with
      systemic inflammation, such as neoplasia, infection and autoimmune disease. We
      report on a 46-year-old Caucasian male with a 3-month history of rheumatoid
      arthritis presenting with dramatic weight loss and dysphagia. Computer tomography
      revealed multiple lesions in the liver and the spleen, strongly suggesting
      malignant disease of unknown origin. Surprisingly, on biopsy, the liver lesions
      drained pus. Workup revealed that the abscesses resulted from gastric
      perforation, which was the consequence of NSAR therapy for rheumatoid arthritis.
      Antibiotic therapy was initiated, abscesses diminished and dysfunctional
      deglutition improved. This unique case demonstrates in a dramatic way the
      difficulties in daily clinical practice to differentiate between paraneoplasia,
      infection and autoimmune disease and the potentially life-threatening
      consequences of their therapy.

PMID- 16981977
TI  - A large splenic cyst mimicking diabetic gastroparesis.
AB  - Splenic cysts are rare, many of which are asymptomatic and incidental finding. We
      report an interesting case of a large incidental splenic cyst in a young diabetic
      patient who presented with diabetic ketoacidosis and mimicking gastroparesis. The
      differential diagnosis and management of splenic cysts is discussed.

PMID- 16981978
TI  - A case of haemangiopericytoma-associated hypoglycaemia: Beneficial effect of
      treatment with radiotherapy.
AB  - A 72-year-old lady presented with recurrent hypoglycaemia and a large pelvic
      mass. Hypoglycaemia was accompanied by undetectable serum insulin and c-peptide
      and high insulin-like growth factor II (IGFII) to IGFI ratio. She had undergone
      successful resection of a large bladder haemangiopericytoma 7 years earlier. A
      core biopsy was performed, and histology confirmed the recurrence of the
      haemangiopericytoma. Local palliative radiotherapy resulted in the reduction of
      IGFII level and IGFII to IGFI ratio and increased insulin, c-peptide and growth
      hormone (GH) level with long-term amelioration of hypoglycaemic episodes.
      Clinically and biochemically, radiotherapy was more effective than GH therapy.

PMID- 16981979
TI  - Diabetic erectile dysfunction--an indicator of generalised endothelial function
      per se?
AB  - Erectile dysfunction (ED) affects up to 70% of men with diabetes. However, the
      pathophysiology of ED in diabetes remains uncertain with both neuronal and
      vascular factors cited. We examined whether ED is an indicator of generalized
      endothelial dysfunction. A unique group of diabetic patients free from
      established conventional cardiac risk factors were investigated. Forearm
      bloodflow responses to nitroprusside and acetylcholine on 11 diabetic men with ED
      and 11 potent diabetic men were measured by venous plethysmography. Patient
      characteristics between the impotent and potent patients were similar except for
      Hba1c which was higher in the group with ED (8.35% vs. 7.03%: p = 0.003). Both
      groups showed increases in FBF to incremental infusions of nitroprusside and
      acetylcholine but the area under curve (AUC) were similar in the ED and the non
      ED groups (p = 0.16 and p = 0.17, respectively). We demonstrated that ED in
      patients with type 2 diabetes is not associated with additional generalized
      endothelial dysfunction.

PMID- 16981980
TI  - Transdermal buprenorphine in pain management--experiences from clinical practice:
      Five case studies.
AB  - Buprenorphine is a semi-synthetic opioid derived from thebaine. The transdermal
      formulation of buprenorphine has been available in Belgium for 3 years, during
      which time the Pain Clinic of the St Elisabeth of Verviers Hospital has gained
      experience in the use of transdermal buprenorphine for the treatment of moderate
      to-severe pain. This paper presents four cases of chronic, non-malignant pain,
      and one case of chronic cancer pain. By starting patients on low doses and slowly
      titrating upwards, transdermal buprenorphine matrix patches provided effective
      analgesia and were well tolerated. Low doses of transdermal buprenorphine were
      created by cutting the smallest available matrix patch (35 mug/h) into halves or
      quarters. The initial dose was then gradually titrated upwards to the dose needed
      for optimum pain relief by the patients. No problems were encountered in
      switching patients from prior analgesic therapy with other opioids to transdermal
      buprenorphine.

PMID- 16981981
TI  - Accuracy and feasibility of point-of-care and continuous blood glucose analysis
      in critically ill ICU patients.
AB  - INTRODUCTION: To obtain strict glucose regulation, an accurate and feasible
      bedside glucometry method is essential. We evaluated three different types of
      point-of-care glucometry in seriously ill intensive care unit (ICU) patients. The
      study was performed as a single-centre, prospective, observational study in a 12
      bed medical ICU of a university hospital. METHODS: Patients with an expected ICU
      stay of more than 48 hours were included. Because the reference laboratory
      delivers glucose values after approximately 30 to 60 minutes, which is too slow
      to use in a glucose regulation protocol and for calibration of the subcutaneous
      continuous glucose monitoring system (CGMS) (CGMS System Gold), we first
      validated the ICU-based blood gas/glucose analyser ABL715 (part 1 of the study).
      Subsequently, part 2 was performed: after inserting (and calibrating) the
      subcutaneous CGMS, heparinised arterial blood samples were drawn from an arterial
      line every 6 hours and analysed on both the Precision PCx point-of-care meter
      using test strips and on the blood gas/glucose analyser ABL715. CGMS glucose data
      were downloaded after 24 to 72 hours. The results of the paired measurements were
      analysed as a scatter plot by the method of Bland and Altman and were expressed
      as a correlation coefficient. RESULTS: Part 1: Four hundred and twenty-four blood
      samples were drawn from 45 critically ill ICU patients. The ICU-based blood
      gas/glucose analyser ABL715 provided a good estimate of conventional laboratory
      glucose assessment: the correlation coefficient was 0.95. In the Clarke error
      grid, 96.8% of the paired measurements were in the clinically acceptable zones A
      and B. Part 2: One hundred sixty-five paired samples were drawn from 19 ICU
      patients. The Precision PCx point-of-care meter showed a correlation coefficient
      of 0.89. Ninety-eight point seven percent of measurements were within zones A and
      B. The correlation coefficient for the subcutaneous CGMS System Gold was 0.89.
      One hundred percent of measurements were within zones A and B. CONCLUSION: The
      ICU-based blood glucose analyser ABL715 is a rapid and accurate alternative for
      laboratory glucose determination and can serve as a standard for ICU blood
      glucose measurements. The Precision PCx is a good alternative, but feasibility
      may be limited because of the blood sample handling. The subcutaneous CGMS System
      Gold is promising, but real-time glucose level reporting is necessary before it
      can be of clinical use in the ICU. When implementing a glucose-insulin algorithm
      in patient care or research, one should realise that the absolute glucose level
      may differ systematically among various measuring methods, influencing targeted
      glucose levels.

PMID- 16981982
TI  - Evolution of vaccination rates after the implementation of a free systematic
      pneumococcal vaccination in Catalonian older adults: 4-years follow-up.
AB  - BACKGROUND: The systematic vaccination with 23-valent polysaccharide pneumococcal
      vaccine (PPV) was introduced as a strategic objective of health for all the
      people over 65 in Catalonia in 1999. We analysed the evolution of the
      pneumococcal vaccination rates from 2000 to 2003. METHODS: We conducted a
      retrospective population-based study including all the individuals 65 years or
      older assigned to 8 Primary Care Centres (PCCs) in Tarragona (Catalonia, Spain),
      who figured in the administrative population databases on 31 December 2003 (n =
      10,410 persons). We assessed whether every person had received PPV during the
      last four years (2000 to 2003) or whether they had received it before January
      2000. Data sources were the computerised clinical records of the 8 participating
      PCCs, which included adult vaccination registries and diagnoses coded of
      International Classification of Diseases 9th REVIEW RESULTS: The overall
      vaccination uptake increased to 38.6% at the end of 2000. Global accumulated
      coverages increased more slowly the following years: 44.4% in 2001, 50.9% in
      2002, and 53.1% at the end of 2003. Vaccine uptake varied significantly according
      to age (46.7% in people 65-74 years-old, 60.9% in people 75 years or more; p <
      0.001) and number of diseases or risk factors (DRFs) for pneumonia (47.1%
      vaccinated in people without DRFs, 56.8% in patients with one DRF, and 62.2% in
      patients with two or more DRFs; p < 0.001). The highest coverages were observed
      among those patients with: diabetes (65.9%), active neoplasia (64.8%), history of
      stroke (63.7%), and chronic lung disease (63.5%). The lowest uptake was observed
      among smokers (48.7%). DISCUSSION: The pneumococcal vaccination coverage
      increased quickly after the introduction of the recommendation for free
      vaccination in all the elderly people (with and without risk factors), but two
      years after the improvement the coverage became stable and increased slowly.

PMID- 16981983
TI  - Would artificial neural networks implemented in clinical wards help nephrologists
      in predicting epoetin responsiveness?
AB  - BACKGROUND: Due to its strong intra- and inter-individual variability, predicting
      the ideal erythropoietin dose is a difficult task. The aim of this study was to
      re-evaluate the impact of the main parameters known to influence the
      responsiveness to epoetin beta and to test the performance of artificial neural
      networks (ANNs) in predicting the dose required to reach the haemoglobin target
      and the monthly dose adjustments. METHODS: We did a secondary analysis of the
      survey on Anaemia Management in dialysis patients in Switzerland; a prospective,
      non-randomized observational study, enrolling 340 patients of 26 centres and in
      order to have additional information about erythropoietin responsiveness, we
      included a further 92 patients from the Renal Services of the Ente Ospedaliero
      Cantonale, Bellinzona, Switzerland. The performance of ANNs in predicting the
      epoetin dose was compared with that of linear regressions and of nephrologists in
      charge of the patients. RESULTS: For a specificity of 50%, the sensitivity of
      ANNs compared with linear regressions in predicting the erythropoietin dose to
      reach the haemoglobin target was 78 vs. 44% (P < 0.001). The ANN built to predict
      the monthly adaptations in erythropoietin dose, compared with the nephrologists'
      opinion, allowed to detect 48 vs. 25% (P < 0.05) of the patients treated with an
      insufficient dose with a specificity of 92 vs. 83% (P < 0.05). CONCLUSION: In
      predicting the erythropoietin dose required for an individual patient and the
      monthly dose adjustments ANNs are superior to nephrologists' opinion. Thus, ANN
      may be a useful and promising tool that could be implemented in clinical wards to
      help nephrologists in prescribing erythropoietin.

PMID- 16981984
TI  - Population-associated differences between the phase variable LPS biosynthetic
      genes of Helicobacter pylori.
AB  - BACKGROUND: Population structures are normally determined using genes under
      minimal functional selection. In this study we have assessed genes that are not
      always essential, show differences in alleles between strains, and are involved
      in the directly host-selectable phenotype of LPS biosynthesis. RESULTS: Eight
      complete LPS biosynthesis genes, seven of which are associated with phase
      variation in some or all strains of Helicobacter pylori, have been sequenced and
      their divergence analyzed. The differences observed indicate that recombination
      within these genes largely reflects exchange between strains within the
      population lineages previously determined on the basis of MLST using housekeeping
      genes. This indicates that the differences that are used for MLST are likely to
      broadly associate with genes under functional selection, and differences in
      strain behaviour. However, instances of exchange between the subpopulations were
      identified, including the hpAfrica2 subpopulation. Further, there were other
      differences in gene complements and the chromosomal location of genes indicative
      of greater diversity within the population than is revealed by the available
      genome sequences and comparative genome hybridization studies. CONCLUSION: These
      results indicate that the described population structure based upon MLST is
      broadly a good basis for studying the biology of H. pylori, but that individual
      alleles may not follow these associations. As a consequence, when working in
      unsequenced strains, it is necessary to carefully check the presence, sequence,
      and distribution of any individual gene of interest.

PMID- 16981985
TI  - Sexual behavior and awareness of Chinese university students in transition with
      implied risk of sexually transmitted diseases and HIV infection: a cross
      sectional study.
AB  - BACKGROUND: The vulnerability of young people to HIV and the recent emergence of
      the HIV epidemic in China have made it urgent to assess and update the HIV/STD
      risk profile of Chinese young people. METHODS: A self-administered questionnaire
      survey with cross-sectional design was conducted among 22,493 undergraduate
      students in two universities in Ningbo, China. Bivariate trend analysis and
      multiple logistic regression analysis were used to compare sexual behaviors and
      awareness between grades. RESULTS: Of respondents, 17.6% of males and 8.6% of
      females reported being sexually active. Condom was reported never/rarely used by
      35% of sexually active students in both genders in the previous year. Pregnancy
      and induced abortion had each been experienced by about 10% of sexually active
      female students and the female partners of male students, and about 1.5% of
      sexually active students of both genders reported being diagnosed with an STD.
      Multivariate analysis revealed that students in lower grades, compared to those
      in higher grades, were more likely to have become sexually active before
      university, to have become aware of sex before high school, and to have been
      exposed to pornographic media before the age of 17 years, and for sexually active
      respondents of both genders, to have engaged in sex without using a condom.
      CONCLUSION: Sexual behaviors of Chinese university students are poorly protected
      and sexual behaviors and awareness may have been undergoing rapid change,
      becoming active earlier and more risky. If this trend continues, vulnerable
      sexual network will grow among them that allow more expansion of sexually
      transmitted diseases and HIV.

PMID- 16981986
TI  - Accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium in
      critically ill patients treated with intravenous voriconazole under renal
      replacement therapy.
AB  - BACKGROUND: Voriconazole was introduced for the treatment of life-threatening
      fungal infections. The intravenous form includes the solvent vehicle
      sulphobutylether beta cyclodextrin sodium which shows an impaired clearance under
      intermittent dialysis therapy. This investigation aimed to determine first
      clinical data on sulphobutylether beta cyclodextrin sodium blood levels to verify
      the risk for accumulation. METHODS: In four patients suffering from renal
      insufficiency and intermittent dialysis therapy who needed a treatment with
      intravenous voriconazole as a reserve antifungal at the intensive care unit of
      the Mainz University Hospital the trough levels of voriconazole and
      sulphobutylether beta cyclodextrin sodium were measured. RESULTS: A 75-year-old
      woman showed a maximal sulphobutylether beta cyclodextrin sodium plasma level of
      145 microg/ml in the initial phase. After a few days renal function recovered and
      the plasma levels came down to less than 20 microg/ml. In contrast to this
      patient with a recovery of renal function the remaining three patients showed
      renal failure during the complete period of intravenous treatment with
      voriconazole. In these patients an accumulation of sulphobutylether beta
      cyclodextrin sodium plasma levels was determined with a maximum of 523 mug/ml in
      a 18-year-old man, 409 microg/ml in a 57-year-old man, and 581 microg/ml in a 47
      year-old man. CONCLUSION: The present data indicate an accumulation of
      sulphobutylether beta cyclodextrin sodium in patients treated with intravenous
      voriconazole and dialysis therapy. Fortunately, no toxic effects were observed,
      although the accumulated dose values were lower but comparable with those used in
      previous toxicity studies with animals.

PMID- 16981987
TI  - Molecular and clinical analyses of 84 patients with tuberous sclerosis complex.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disease
      characterized by the development of multiple hamartomas in many internal organs.
      Mutations in either one of 2 genes, TSC1 and TSC2, have been attributed to the
      development of TSC. More than two-thirds of TSC patients are sporadic cases, and
      a wide variety of mutations in the coding region of the TSC1 and TSC2 genes have
      been reported. METHODS: Mutational analysis of TSC1 and TSC2 genes was performed
      in 84 Taiwanese TSC families using denaturing high-performance liquid
      chromatography (DHPLC) and direct sequencing. RESULTS: Mutations were identified
      in a total of 64 (76 %) cases, including 9 TSC1 mutations (7 sporadic and 2
      familial cases) and 55 TSC2 mutations (47 sporadic and 8 familial cases). Thirty
      one of the 64 mutations found have not been described previously. The phenotype
      association is consistent with findings from other large studies, showing that
      disease resulting from mutations to TSC1 is less severe than disease due to TSC2
      mutation. CONCLUSION: This study provides a representative picture of the
      distribution of mutations of the TSC1 and TSC2 genes in clinically ascertained
      TSC cases in the Taiwanese population. Although nearly half of the mutations
      identified were novel, the kinds and distribution of mutation were not different
      in this population compared to that seen in larger European and American studies.

PMID- 16981988
TI  - Obesity, physical activity, and the urban environment: public health research
      needs.
AB  - Persistent trends in overweight and obesity have resulted in a rapid research
      effort focused on built environment, physical activity, and overweight. Much of
      the focus of this research has been on the design and form of suburbs. It
      suggests that several features of the suburban built environment such as low
      densities, poor street connectivity and the lack of sidewalks are associated with
      decreased physical activity and an increased risk of being overweight. But
      compared to suburban residents, inner city populations have higher rates of
      obesity and inactivity despite living in neighborhoods that are dense, have
      excellent street connectivity and who's streets are almost universally lined with
      sidewalks. We suggest that the reasons for this apparent paradox are rooted in
      the complex interaction of land use, infrastructure and social factors affecting
      inner city populations. Sometimes seemingly similar features are the result of
      very different processes, necessitating different policy responses to meet these
      challenges. For example, in suburbs, lower densities can result from government
      decision making that leads to restrictive zoning and land use issues. In the
      inner city, densities may be lowered because of abandonment and disinvestment. In
      the suburbs, changes in land use regulations could result in a healthier built
      environment. In inner cities, increasing densities will depend on reversing
      economic trends and investment decisions that have systematically resulted in
      distressed housing, abandoned buildings and vacant lots. These varying issues
      need to be further studied in the context of the totality of urban environments,
      incorporating what has been learned from other disciplines, such as economics and
      sociology, as well as highlighting some of the more successful inner city policy
      interventions, which may provide examples for communities working to improve
      their health. Certain disparities among urban and suburban populations in obesity
      and overweight, physical activity and research focus have emerged that are timely
      to address. Comparable research on the relationship of built environment and
      health is needed for urban, especially inner city, neighborhoods.

PMID- 16981989
TI  - Bowel cancer screening in England: a qualitative study of GPs' attitudes and
      information needs.
AB  - BACKGROUND: The National Health Service Bowel Cancer Screening Programme is to be
      introduced in England during 2006. General Practitioners are a potentially
      important point of contact for participants throughout the screening process. The
      aims of the study were to examine GPs' attitudes and information needs with
      regard to bowel cancer screening, with a view to developing an information pack
      for primary care teams that will be circulated prior to the introduction of the
      programme. METHODS: 32 GPs participated in semi-structured telephone interviews.
      18 of these had participated in the English Bowel Screening Pilot, and 14 had
      not. Interviews covered attitudes towards the introduction of the Bowel Cancer
      Screening Programme, expected or actual increases in workload, confidence in
      promoting informed choice, and preferences for receiving information about the
      programme. RESULTS: GPs in the study were generally positive about the
      introduction of the Bowel Cancer Screening Programme. A number of concerns were
      identified by GPs who had not taken part in the pilot programme, particularly
      relating to patient welfare, patient participation, and increased workload. GPs
      who had taken part in the pilot reported holding similar concerns prior to their
      involvement. However, in many cases these concerns were not confirmed through GPs
      experiences with the pilot. A number of specific information needs were
      identified by GPs to enable them to provide a supportive role to participants in
      the programme. CONCLUSION: The study has found considerable GP support for the
      introduction of the new Bowel Cancer Screening Programme. Nonetheless, GPs hold
      some significant reservations regarding the programme. It is important that the
      information needs of GPs and other members of the primary care team are addressed
      prior to the roll-out of the programme so they are equipped to promote informed
      choice and provide support to patients who consult them with queries regarding
      screening.

PMID- 16981990
TI  - Overweight, physical activity, tobacco and alcohol consumption in a cross
      sectional random sample of German adults.
AB  - BACKGROUND: There is a current paucity of data on the health behaviour of non
      selected populations in Central Europe. Data on health behaviour were collected
      as part of the EMIL study which investigated the prevalence of infection with
      Echinococcus multilocularis and other medical conditions in an urban German
      population. METHODS: Participating in the present study were 2,187 adults (1,138
      females [52.0%]; 1,049 males [48.0%], age: 18-65 years) taken from a sample of
      4,000 persons randomly chosen from an urban population. Data on health behaviour
      like physical activity, tobacco and alcohol consumption were obtained by means of
      a questionnaire, documentation of anthropometric data, abdominal ultrasound and
      blood specimens for assessment of chemical parameters. RESULTS: The overall rate
      of participation was 62.8%. Of these, 50.3% of the adults were overweight or
      obese. The proportion of active tobacco smokers stood at 30.1%. Of those surveyed
      38.9% did not participate in any physical activity. Less than 2 hours of leisure
      time physical activity per week was associated with female sex, higher BMI (Body
      Mass Index), smoking and no alcohol consumption. Participants consumed on average
      12 grams of alcohol per day. Total cholesterol was in 62.0% (>5.2 mmol/l) and
      triglycerides were elevated in 20.5% (> or = 2.3 mmol/l) of subjects studied.
      Hepatic steatosis was identified in 27.4% of subjects and showed an association
      with male sex, higher BMI, higher age, higher total blood cholesterol, lower HDL,
      higher triglycerides and higher ALT. CONCLUSION: This random sample of German
      urban adults was characterised by a high prevalence of overweight and obesity.
      This and the pattern of alcohol consumption, smoking and physical activity can be
      considered to put this group at high risk for associated morbidity and underscore
      the urgent need for preventive measures aimed at reducing the significantly
      increased health risk.

PMID- 16981991
TI  - Event-related potentials when identifying or color-naming threatening schematic
      stimuli in spider phobic and non-phobic individuals.
AB  - BACKGROUND: Previous studies revealed increased parietal late positive potentials
      (LPPs) in response to spider pictures in spider phobic individuals. This study
      searched for basic features of fear-relevant stimuli by investigating whether
      schematic spider images are sufficient to evoke differential behavioral as well
      as differential early and late ERP responses in spider phobic, social phobic (as
      a clinical control group), and non-phobic control participants. METHODS:
      Behavioral and electrophysiological correlates of the processing of schematic
      spider and flower images were investigated while participants performed a color
      (emotional Stroop) and an object identification task. Stimuli were schematic
      pictures of spiders and flowers matched with respect to constituting visual
      elements. RESULTS: Consistent with previous studies using photographic spider
      pictures, spider phobic persons showed enhanced LPPs when identifying schematic
      spiders compared to schematic flowers. In addition, spider phobic individuals
      showed generally faster responses than the control groups. This effect was
      interpreted as evidence for an increased general behavioral hypervigilance in
      this anxiety disorder group. Furthermore, both phobic groups showed enhanced P100
      amplitudes compared to controls, which was interpreted as evidence for an
      increased (cortical) hypervigilance for incoming stimuli in phobic patients in
      general. Finally, all groups showed faster identification of and larger N170
      amplitudes in response to schematic spider than flower pictures. This may reflect
      either a general advantage for fear-relevant compared to neutral stimuli, or
      might be due to a higher level of expertise in processing schematic spiders as
      compared to the more artificially looking flower stimuli. CONCLUSION: Results
      suggest that schematic spiders are sufficient to prompt differential responses in
      spider-fearful and spider-non-fearful persons in late ERP components. Early ERP
      components, on the other hand, seem to be modified by anxiety status per se,
      which is consistent with recent theories on general hypervigilance in the anxiety
      disorder spectrum.

PMID- 16981992
TI  - Adjuvant endocrine therapy for postmenopausal breast cancer in the era of
      aromatase inhibitors: an update.
AB  - There is overwhelming evidence that optimal adjuvant endocrine therapy for
      hormone sensitive breast cancer in postmenopausal women should include a third
      generation aromatase inhibitor (AI). On current evidence, adjuvant anstrozole or
      letrozole should be used upfront in such patients especially in those with high
      risk disease (node positive and/or tumours > 2 cm). The sequential approach of
      tamoxifen for 2-3 years followed by exemestane or anastrozole for 2-3 years is a
      reasonable alternative to 5 years of AI monotherapy in patients with low risk
      disease (node negative and tumour smaller than 2 cm) especially if the tumour is
      positive for estrogen and progesterone receptors.Node-positive patients
      completing 5 years of adjuvant tamoxifen should be offered letrozole for up 48
      months. Further research is required to establish the long-term cardiovascular
      safety of AIs especially that of letrozole and exmestane, the optimal AI to use,
      duration of AI therapy and whether monotherapy with an AI for 5 years is superior
      to sequencing an AI after 2-3 years of tamoxifen. The bone mineral density (BMD)
      should be measured at baseline and monitored during therapy in women being
      treated with AIs. Anti-osteoporosis agents should such as bisphosphonates should
      be considered in patients at high risk of bone fractures.

PMID- 16981993
TI  - Correlated fragile site expression allows the identification of candidate fragile
      genes involved in immunity and associated with carcinogenesis.
AB  - BACKGROUND: Common fragile sites (cfs) are specific regions in the human genome
      that are particularly prone to genomic instability under conditions of
      replicative stress. Several investigations support the view that common fragile
      sites play a role in carcinogenesis. We discuss a genome-wide approach based on
      graph theory and Gene Ontology vocabulary for the functional characterization of
      common fragile sites and for the identification of genes that contribute to
      tumour cell biology. RESULTS: Common fragile sites were assembled in a network
      based on a simple measure of correlation among common fragile site patterns of
      expression. By applying robust measurements to capture in quantitative terms the
      non triviality of the network, we identified several topological features clearly
      indicating departure from the Erdos-Renyi random graph model. The most important
      outcome was the presence of an unexpected large connected component far below the
      percolation threshold. Most of the best characterized common fragile sites
      belonged to this connected component. By filtering this connected component with
      Gene Ontology, statistically significant shared functional features were
      detected. Common fragile sites were found to be enriched for genes associated to
      the immune response and to mechanisms involved in tumour progression such as
      extracellular space remodeling and angiogenesis. Moreover we showed how the
      internal organization of the graph in communities and even in very simple
      subgraphs can be a starting point for the identification of new factors of
      instability at common fragile sites. CONCLUSION: We developed a computational
      method addressing the fundamental issue of studying the functional content of
      common fragile sites. Our analysis integrated two different approaches. First,
      data on common fragile site expression were analyzed in a complex networks
      framework. Second, outcomes of the network statistical description served as
      sources for the functional annotation of genes at common fragile sites by means
      of the Gene Ontology vocabulary. Our results support the hypothesis that fragile
      sites serve a function; we propose that fragility is linked to a coordinated
      regulation of fragile genes expression.

PMID- 16981994
TI  - Semi-supervised discovery of differential genes.
AB  - BACKGROUND: Various statistical scores have been proposed for evaluating the
      significance of genes that may exhibit differential expression between two or
      more controlled conditions. However, in many clinical studies to detect clinical
      marker genes for example, the conditions have not necessarily been controlled
      well, thus condition labels are sometimes hard to obtain due to physical,
      financial, and time costs. In such a situation, we can consider an unsupervised
      case where labels are not available or a semi-supervised case where labels are
      available for a part of the whole sample set, rather than a well-studied
      supervised case where all samples have their labels. RESULTS: We assume a latent
      variable model for the expression of active genes and apply the optimal discovery
      procedure (ODP) proposed by Storey (2005) to the model. Our latent variable model
      allows gene significance scores to be applied to unsupervised and semi-supervised
      cases. The ODP framework improves detectability by sharing the estimated
      parameters of null and alternative models of multiple tests over multiple genes.
      A theoretical consideration leads to two different interpretations of the latent
      variable, i.e., it only implicitly affects the alternative model through the
      model parameters, or it is explicitly included in the alternative model, so that
      the interpretations correspond to two different implementations of ODP. By
      comparing the two implementations through experiments with simulation data, we
      have found that sharing the latent variable estimation is effective for
      increasing the detectability of truly active genes. We also show that the
      unsupervised and semi-supervised rating of genes, which takes into account the
      samples without condition labels, can improve detection of active genes in real
      gene discovery problems. CONCLUSION: The experimental results indicate that the
      ODP framework is effective for hypotheses including latent variables and is
      further improved by sharing the estimations of hidden variables over multiple
      tests.

PMID- 16981995
TI  - Substance P induces localization of MIF/alpha1-inhibitor-3 complexes to umbrella
      cells via paracellular transit through the urothelium in the rat bladder.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is released into the
      intraluminal fluid during bladder inflammation in the rat complexed to alpha1
      inhibitor-3 (A1-I3; a rodent proteinase inhibitor in the alpha-macroglobulin
      family). The location of A1-I3 in the bladder had not been investigated.
      Therefore, we examined the location of A1-I3 and MIF/A1-I3 complexes in the
      bladder and changes due to experimental inflammation. METHODS: Anesthetized male
      rats had bladders removed with no treatment (intact) or were injected with
      Substance P (SP; s.c.; saline vehicle). After one hour intraluminal fluid was
      removed, bladder was excised and MIF and A1-I3 levels were determined using ELISA
      and/or western-blotting. MIF co-immunoprecipitation determined MIF/A1-I3
      complexes in the bladder. Bladder sections were immunostained for A1-I3 and
      MIF/A1-I3. RESULTS: A1-I3 immunostaining was observed in interstitial spaces
      throughout the bladder (including submucosa) but not urothelium in intact and
      saline-treated rats. RT-PCR showed that the bladder does not synthesize A1-I3,
      therefore, A1-I3 in the interstitial space of the bladder must be plasma derived.
      In SP-treated rats, A1-I3 in the bladder increased and A1-I3 was observed
      traversing through the urothelium. Umbrella cells that do not show MIF and/or A1
      I3 immunostaining in intact or saline-treated rats, showed co-localization of MIF
      and A1-I3 after SP-treatment. Western blotting demonstrated that in the bladder
      MIF formed non-covalent interactions and also binds covalently to A1-I3 to form
      high molecular weight MIF/A1-I3 complexes (170, 130 and 75-kDa, respectively,
      verified by co-immunoprecipitation). SP-induced inflammation selectively reduced
      170-kDa MIF/A1-I3 in the bladder while increasing 170 and 130-kDa MIF/A1-I3 in
      the intraluminal fluid. CONCLUSION: A1-I3 and MIF/A1-I3 complexes are resident in
      bladder interstitium. During SP-induced inflammation, MIF/A1-I3 complexes are
      released from the bladder into the lumen. Binding of MIF/A1-I3 complexes to
      urothelial cells during inflammation suggests these complexes participate in the
      inflammatory reaction through activation of receptors for MIF and/or for A1-I3.

PMID- 16981996
TI  - Exploring the role of GIS during community health assessment problem solving:
      experiences of public health professionals.
AB  - BACKGROUND: A Community health assessment (CHA) involves the use of Geographic
      Information Systems (GIS) in conjunction with other software to analyze health
      and population data and perform numerical-spatial problem solving. There has been
      little research on identifying how public health professionals integrate this
      software during typical problem solving scenarios. A better understanding of this
      is needed to answer the "What" and the "How". The "What" identifies the specific
      software being used and the "How" explains the way they are integrated together
      during problem solving steps. This level of understanding will highlight the role
      of GIS utilization during problem solving and suggest to developers how GIS can
      be enhanced to better support data analysis during community health assessment.
      RESULTS: An online survey was developed to identify the information technology
      used during CHA analysis. The tasks were broken down into steps and for our
      analysis these steps were categorized by action: Data Management/Access, Data
      Navigation, Geographic Comparison, Detection of Spatial Boundaries, Spatial
      Modelling, and Ranking Analysis. 27 CHA professionals completed the survey, with
      the majority of participants (14) being from health departments. Statistical
      software (e.g. SPSS) was the most popular software for all but one of the types
      of steps. For this step (detection of spatial boundaries), GIS was identified as
      the most popular technology. CONCLUSION: Most CHA professionals indicated they
      use statistical software in conjunction with GIS. The statistical software
      appears to drive the analysis, while GIS is used primarily for simple spatial
      display (and not complex spatial analysis). This purpose of this survey was to
      thoroughly examine into the process of problem solving during community health
      assessment data analysis and to gauge how GIS is integrated with other software
      for this purpose. These findings suggest that GIS is used more for spatial
      display while other software such as statistical packages (the "What") are used
      to drive data management, data navigation, and data calculation (the "How").
      Focusing at the level of how public health problems are solved, can shed light on
      how GIS technology can be enhanced to encompass a stronger role during community
      health assessment problem solving.

PMID- 16981997
TI  - Kinetics of progenitor hemopoetic stem cells in sepsis: correlation with patients
      survival?
AB  - BACKGROUND: Current theories underline the crucial role of pro-inflammatory
      mediators produced by monocytes for the pathogenesis of sepsis. Since monocytes
      derive from progenitor hemopoetic cells, the kinetics of stem cells was studied
      in peripheral blood of patients with sepsis. METHODS: Blood was sampled from 44
      patients with septic syndrome due to ventilator-associated pneumonia on days 1,
      3, 5 and 7 upon initiation of symptoms. Concentrations of tumour necrosis factor
      alpha (TNFalpha), interleukin (IL)-6, IL-8 and G-CSF were estimated by ELISA.
      CD34/CD45 cells were determined after incubation with anti-CD45 FITC and anti
      CD34 PE monocloncal antibodies and flow cytometric analysis. Samples from eight
      healthy volunteers served as controls. RESULTS: Median of CD34/CD45 absolute
      count of controls was 1.0/mul. Respective values of the total study population
      were 123.4, 112.4, 121.5 and 120.9/mul on days 1, 3, 5 and 7 (p < 0.0001 compared
      to controls). Positive correlations were found between the absolute CD34/CD45
      count and the absolute monocyte count on days 1, 5 and 7. Survival was prolonged
      among patients with less than 310/microl CD34/CD45 cells on day 1 compared to
      those with more than 310/microl of CD34/CD45 cells (p: 0.022). Hazard ratio for
      death due to sepsis was 5.47 (p: 0.039) for CD34/CD45 cells more than 310/microl.
      Median IL-6 on day 1 was 56.78 and 233.85 pg/ml respectively for patients with
      less than 310/microl and more than 310/microl CD34/CD45 cells (p: 0.021).
      CONCLUSION: Stem cells are increased in peripheral blood over all days of follow
      up compared to healthy volunteers. Patients with counts on day 1 less than
      310/microl are accompanied by increased survival compared to patients with more
      than 310/microl.

PMID- 16981998
TI  - Gene expression analysis indicates extensive genotype-specific crosstalk between
      the conjugative F-plasmid and the E. coli chromosome.
AB  - BACKGROUND: Plasmids are an important component of the bacterial genome, but the
      crosstalk between genes encoded on the chromosome and on the plasmid is still
      poorly understood. RESULTS: We performed a large-scale survey for genes on the E.
      coli chromosome that are affected by the presence of the conjugative F-plasmid
      (crosstalk). The expression pattern of about 4% (107 genes) of the genes encoded
      by the chromosome was affected by the presence of the F-plasmid. Comparing two
      different Escherichia coli strains, MG1655 and DH5alpha, we found a strong host
      genotype-specific crosstalk of the host chromosome with the F-plasmid. About 88%
      of the genes affected by the presence of the F-plasmid showed a significant
      plasmid by host genotype interaction, i.e. the presence of the F-plasmid resulted
      in a different gene expression in the two host genotypes. Less than 12% of the
      genes showed an additive effect of gene expression, i.e. host genotype
      independent crosstalk between plasmid and host chromosome. CONCLUSION: We propose
      that epistatic effects also contribute to the maintenance of F-plasmids in
      natural populations.

PMID- 16981999
TI  - Uncommon sarcomas of the uterine cervix: a review of selected entities.
AB  - Sarcomas constitute less than 1% of all cervical malignancies. With over 150
      reported cases, rhabdomyosarcomas represent the most commonly reported sarcoma at
      this location. In this report, a select group of the more uncommon sarcomas of
      the uterine cervix are reviewed, including all previously reported examples of
      leiomyosarcoma, liposarcoma, alveolar soft part sarcoma, Ewing sarcoma/primitive
      neuroectodermal tumor, undifferentiated endocervical sarcoma, and malignant
      peripheral nerve sheath tumor (MPNST). Emphasis is placed on any distinctive
      clinicopathologic features of these entities at this unusual location.

PMID- 16982000
TI  - Asymmetric aza-Diels-Alder reaction of Danishefsky's diene with imines in a
      chiral reaction medium.
AB  - The asymmetric aza-Diels-Alder reaction of chiral imines with Danishefsky's diene
      in chiral ionic liquids provides the corresponding cycloadduct with moderate to
      high diastereoselectivity. The reaction has proved to perform better at room
      temperature in ionic liquids without either Lewis acid catalyst or organic
      solvent. Chiral ionic liquids are recycled while their efficiency is preserved.

PMID- 16982001
TI  - The association of comorbidities, utilization and costs for patients identified
      with low back pain.
AB  - BACKGROUND: Existing studies have examined the high prevalence of LBP along with
      the high treatment costs of patients with low back pain (LBP). Various factors
      have been shown to be correlated or predictive of chronic or episodic LBP
      including the characteristics of the initial episode, pain, comorbid conditions,
      psychosocial issues, and opiate use. This study replicates and extends earlier
      studies by examining the association of patient characteristics including
      baseline comorbidities with patterns of healthcare service use and cost. METHODS:
      This is a retrospective analysis of measures of comorbidities, healthcare use,
      and cost for patients identified with LBP, stratified by the number of LBP
      episodes. Administrative data associated with outpatient and hospital based care
      for the years 1996 through 2001, were used to identify adult patients with LBP.
      LBP patients continuously enrolled for 12 months prior and 24 months after their
      initial LBP event were included in the study. A LBP episode was identified as the
      number of 30-day periods where a patient had one or more healthcare events with a
      diagnosis consistent with LBP. Chi-square and multivariate regression analyses
      were employed to estimate the variation in utilization and costs. RESULTS: Of
      16,567 patients enrolled, 67% were identified with only one LBP episode and 4.5%
      had > or =6. The prevalence of comorbidities, analgesic use, and healthcare
      service use, varied by the number of back pain episodes. Diabetes, rheumatoid
      arthritis, anxiety, psychotic illness, depression, use of opiates and NSAIDs were
      associated with significant incremental increases in costs (P < .003).
      CONCLUSION: Physical and mental health co-morbidities and measures of analgesic
      use were associated with chronicity, healthcare utilization and costs. Given the
      association of comorbidities and cost for patients with LBP, management
      approaches that are effective across chronic illnesses may prove to be beneficial
      for high cost patients identified with LBP.

PMID- 16982002
TI  - Integrated problem-based learning in the neuroscience curriculum--the SUNY
      Downstate experience.
AB  - BACKGROUND: This paper reports the author's initial experience as Block Director
      in converting a Conventional Curriculum into a problem-based learning model (PBL)
      for teaching Psychopathology. As part of a wide initiative in curriculum reform,
      Psychopathology, which was a six-week course in the second-year medical school
      curriculum, became integrated into a combined Neuroscience block. The study
      compares curriculum conversion at State University of New York (SUNY), Downstate,
      with the experiences at other medical centres that have instituted similar
      curricula reform. METHODS: Student satisfaction with the Conventional and PBL
      components of the Neuroscience curriculum was compared using questionnaires and
      formal discussions between faculty and a body of elected students. The PBL
      experience in Psychopathology was also compared with that of the rest of the
      Neuroscience Block, which used large student groups and expert facilitators,
      while the Psychopathology track was limited to small groups using mentors
      differing widely in levels of expertise. RESULTS: Students appeared to indicate a
      preference toward conventional lectures and large PBL groups using expert
      facilitators in contrast to small group mentors who were not experts. Small PBL
      groups with expert mentors in the Psychopathology track were also rated
      favorably. CONCLUSION: The study reviews the advantages and pitfalls of the PBL
      system when applied to a Neuroscience curriculum on early career development. At
      SUNY, conversion from a Conventional model to a PBL model diverged from that
      proposed by Howard S. Barrows where student groups define the learning objectives
      and problem-solving strategies. In our model, the learning objectives were
      faculty-driven. The critical issue for the students appeared to be the level of
      faculty expertise rather than group size. Expert mentors were rated more
      favorably by students in fulfilling the philosophical objectives of PBL. The
      author, by citing the experience at other major Medical Faculties, makes a
      cautious attempt to address the challenges involved in the conversion of a
      Psychopathology curriculum into a PBL dominated format.

PMID- 16982003
TI  - Analog peptides of type II collagen can suppress arthritis in HLA-DR4 (DRB1*0401)
      transgenic mice.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease associated with the
      recognition of self proteins secluded in diarthrodial joints. We have previously
      established that mice transgenic for the human DR genes associated with RA are
      susceptible to collagen-induced arthritis (CIA) and we have identified a
      determinant of type II collagen (CII(263-270)) that triggers T-cell immune
      responses in these mice. We have also determined that an analog of CII(263-270)
      would suppress disease in DR1 transgenic mice. Because the immunodominant
      determinant is the same for both DR1 transgenic and DR4 transgenic mice, we
      attempted to determine whether the analog peptide that was suppressive in DR1
      transgenic mice would also be effective in suppressing CIA in DR4 transgenic
      mice. We treated DR4 transgenic mice with two analog peptides of CII that
      contained substitutions in the core of the immunodominant determinant: CII(256
      276) (F263N, E266D) and CII(256-270) (F263N, E266A). Mice were observed for CIA,
      and T-cell proliferative responses were determined. Either peptide administered
      at the time of immunization with CII significantly downregulated arthritis.
      Binding studies demonstrated that replacement of the phenylalanine residue in
      position 263 of the CII peptide with asparagine significantly decreased the
      affinity of the peptide for the DR4 molecule. In contrast, replacement of the
      glutamic acid residue in position 266 with aspartic acid or with alanine had
      differing results. Aspartic acid reduced the affinity (35-fold) whereas alanine
      did not. Both peptides were capable of suppressing CIA. With the use of either
      peptide, CII(256-276) (F263N, E266D) or CII(256-270) (F263N, E266A), the
      modulation of CIA was associated with an increase in T-cell secretion of IL-4
      together with a decrease in IFN-gamma. We have identified two analog peptides
      that are potent suppressors of CIA in DR4 transgenic mice. These experiments
      represent the first description of an analog peptide of CII recognized by T cells
      in the context of HLA-DR4 that can suppress autoimmune arthritis.

PMID- 16982004
TI  - Comparison of methods for genomic localization of gene trap sequences.
AB  - BACKGROUND: Gene knockouts in a model organism such as mouse provide a valuable
      resource for the study of basic biology and human disease. Determining which gene
      has been inactivated by an untargeted gene trapping event poses a challenging
      annotation problem because gene trap sequence tags, which represent sequence near
      the vector insertion site of a trapped gene, are typically short and often
      contain unresolved residues. To understand better the localization of these
      sequences on the mouse genome, we compared stand-alone versions of the alignment
      programs BLAT, SSAHA, and MegaBLAST. A set of 3,369 sequence tags was aligned to
      build 34 of the mouse genome using default parameters for each algorithm. Known
      genome coordinates for the cognate set of full-length genes (1,659 sequences)
      were used to evaluate localization results. RESULTS: In general, all three
      programs performed well in terms of localizing sequences to a general region of
      the genome, with only relatively subtle errors identified for a small proportion
      of the sequence tags. However, large differences in performance were noted with
      regard to correctly identifying exon boundaries. BLAT correctly identified the
      vast majority of exon boundaries, while SSAHA and MegaBLAST missed the majority
      of exon boundaries. SSAHA consistently reported the fewest false positives and is
      the fastest algorithm. MegaBLAST was comparable to BLAT in speed, but was the
      most susceptible to localizing sequence tags incorrectly to pseudogenes.
      CONCLUSION: The differences in performance for sequence tags and full-length
      reference sequences were surprisingly small. Characteristic variations in
      localization results for each program were noted that affect the localization of
      sequence at exon boundaries, in particular.

PMID- 16982005
TI  - Breaking down the barriers: fMRI applications in pain, analgesia and analgesics.
AB  - This review summarizes functional magnetic resonance imaging (fMRI) findings that
      have informed our current understanding of pain, analgesia and related phenomena,
      and discusses the potential role of fMRI in improved therapeutic approaches to
      pain. It is divided into 3 main sections: (1) fMRI studies of acute and chronic
      pain. Physiological studies of pain have found numerous regions of the brain to
      be involved in the interpretation of the 'pain experience'; studies in chronic
      pain conditions have identified a significant CNS component; and fMRI studies of
      surrogate models of chronic pain are also being used to further this
      understanding. (2) fMRI studies of endogenous pain processing including placebo,
      empathy, attention or cognitive modulation of pain. (3) The use of fMRI to
      evaluate the effects of analgesics on brain function in acute and chronic pain.
      fMRI has already provided novel insights into the neurobiology of pain. These
      insights should significantly advance therapeutic approaches to chronic pain.

PMID- 16982006
TI  - A genome-wide map of aberrantly expressed chromosomal islands in colorectal
      cancer.
AB  - BACKGROUND: Cancer development is accompanied by genetic phenomena like deletion
      and amplification of chromosome parts or alterations of chromatin structure. It
      is expected that these mechanisms have a strong effect on regional gene
      expression. RESULTS: We investigated genome-wide gene expression in colorectal
      carcinoma (CRC) and normal epithelial tissues from 25 patients using
      oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal
      islands with aberrant gene expression. Of these, 38 islands show a gain in
      expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human
      genes) are located in aberrantly expressed islands. Many chromosomal regions that
      are linked to hereditary colorectal cancer show deregulated expression. Also,
      many known tumor genes localize to chromosomal islands of misregulated expression
      in CRC. CONCLUSION: An extensive comparison with published CGH data suggests that
      chromosomal regions known for frequent deletions in colon cancer tend to show
      reduced expression. In contrast, regions that are often amplified in colorectal
      tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA
      expression. Because for several islands of deregulated expression chromosomal
      aberrations have never been observed, we speculate that additional mechanisms
      (like abnormal states of regional chromatin) also have a substantial impact on
      the formation of co-expression islands in colorectal carcinoma.

PMID- 16982007
TI  - Effect of random and hub gene disruptions on environmental and mutational
      robustness in Escherichia coli.
AB  - BACKGROUND: Genome-wide profiling has allowed the regulatory interaction networks
      of many organisms to be visualised and the pattern of connections between genes
      to be studied. These networks are non-random, following a power-law distribution
      with a small number of well-connected 'hubs' and many genes with only one or a
      few connections. Theoretical work predicts that power-law networks display
      several unique properties. One of the most biologically interesting of these is
      an intrinsic robustness to disturbance such that removal of a random gene will
      have little effect on network function. Conversely, targeted removal of a hub
      gene is expected to have a large effect. RESULTS: We compared the response of
      Escherichia coli to environmental and mutational stress following disruption of
      random or hub genes. We found that disruption of random genes had less effect on
      robustness to environmental stress than did the targeted disruption of hub genes.
      In contrast, random disruption strains were slightly less robust to the effect of
      mutational stress than were hub disruption strains. When we compared the effect
      of each disruption on environmental and mutational stress, we found a negative
      relationship, such that strains that were more environmentally robust tended to
      be less robust to mutational stress. CONCLUSION: Our results demonstrate that
      mutant strains of E. coli respond differently to stress, depending on whether
      random or hub genes are disrupted. This difference indicates that the power-law
      distribution of regulatory interactions has biological significance, making
      random disruptions less deleterious to organisms facing environmental stress.
      That E. coli can reduce the effect of environmental stress without reducing the
      phenotypic effect of additional mutations, indicates that robustness and
      evolvability need not be antagonistic.

PMID- 16982008
TI  - Order is needed to promote linear or quantum changes in nutrition and physical
      activity behaviors: a reaction to 'A chaotic view of behavior change' by Resnicow
      and Vaughan.
AB  - Recently, Drs. Ken Resnicow and Roger Vaughan published a thought-provoking paper
      in the International Journal of Behavioral Nutrition and Physical Activity
      (IJBNPA). They argue that the most often used social-cognition theories in
      behavioral nutrition and physical activity are of limited use. These models
      describe behavior change as a linear event, while Resnicow and Vaughan posit that
      behavior change is more likely to occur in quantum leaps that are impossible to
      predict. They introduce Chaos Theory into the behavioral nutrition and physical
      activity domain as a more valid framework to study the complex process of health
      behavior change. The present paper is a commentary on Resnicow and Vaughan's
      article by Resnicow's opponent in a recent debate-session at the annual meeting
      of the International Society of Behavioral Nutrition and Physical Activity. The
      chair of that meeting, Prof. Tom Baranowski, provides a separate commentary on
      Resnicow and Vaughan's paper also published recently in the IJBNPA. In the
      present commentary I relate Resnicow and Vaughan's paper to the other
      contributions to the Theory debate in the IJBNPA. I recognize the limited success
      of social cognition models, and, next to a better application of these models and
      more thorough research to test these model, also support research to further test
      the quantum and chaotic character of health behavior change. However, if such
      research supports the chaotic and quantum nature of health behavior change, the
      implications for behavioral nutrition and physical activity interventions may be
      limited, because even if behavior change is quantum rather than linear, the
      social cognition models are still relevant to inform interventions to promote
      quantum leaps in behavior change.

PMID- 16982009
TI  - How well do HapMap SNPs capture the untyped SNPs?
AB  - BACKGROUND: The recent advancement in human genome sequencing and genotyping has
      revealed millions of single nucleotide polymorphisms (SNP) which determine the
      variation among human beings. One of the particular important projects is The
      International HapMap Project which provides the catalogue of human genetic
      variation for disease association studies. In this paper, we analyzed the
      genotype data in HapMap project by using National Institute of Environmental
      Health Sciences Environmental Genome Project (NIEHS EGP) SNPs. We first determine
      whether the HapMap data are transferable to the NIEHS data. Then, we study how
      well the HapMap SNPs capture the untyped SNPs in the region. Finally, we provide
      general guidelines for determining whether the SNPs chosen from HapMap may be
      able to capture most of the untyped SNPs. RESULTS: Our analysis shows that HapMap
      data are not robust enough to capture the untyped variants for most of the human
      genes. The performance of SNPs for European and Asian samples are marginal in
      capturing the untyped variants, i.e. approximately 55%. Expectedly, the SNPs from
      HapMap YRI panel can only capture approximately 30% of the variants. Although the
      overall performance is low, however, the SNPs for some genes perform very well
      and are able to capture most of the variants along the gene. This is observed in
      the European and Asian panel, but not in African panel. Through observation, we
      concluded that in order to have a well covered SNPs reference panel, the SNPs
      density and the association among reference SNPs are important to estimate the
      robustness of the chosen SNPs. CONCLUSION: We have analyzed the coverage of
      HapMap SNPs using NIEHS EGP data. The results show that HapMap SNPs are
      transferable to the NIEHS SNPs. However, HapMap SNPs cannot capture some of the
      untyped SNPs and therefore resequencing may be needed to uncover more SNPs in the
      missing region.

PMID- 16982010
TI  - Antimicrobial resistance and patient outcomes: the hazards of adjustment.
AB  - Outcomes studies of infections with resistant bacteria often do not account
      appropriately for intermediate variables--events in the causal pathway between
      the exposure and the outcome--when controlling for confounders. We discuss how
      failure to distinguish between confounders and intermediate variables can bias
      the analysis, and we address methods of approaching this issue.

PMID- 16982011
TI  - An ounce of prevention: noninvasive ventilation to prevent postextubation
      respiratory failure.

PMID- 16982012
TI  - PICCing the best access for your patient.

PMID- 16982013
TI  - Predicting volume responsiveness in spontaneously breathing patients: still a
      challenging problem.
AB  - The prediction of which patients respond to fluid infusion and which patients do
      not is an important issue in the intensive care setting. Assessment of this
      response by monitoring changes in some hemodynamic characteristics in relation to
      spontaneous breathing efforts would be very helpful for the management of the
      critically ill. This unfortunately remains a difficult clinical problem, as
      discussed in the previous issue of the journal. Technical factors and
      physiological factors limit the usefulness of current techniques.

PMID- 16982015
TI  - [Medication errors--many possibilities to improvement].

PMID- 16982016
TI  - [Medication errors on hospital admission].
AB  - INTRODUCTION: This study investigated the number of medication errors on hospital
      admission and the clinical relevance of these errors. The new personal electronic
      medicine profile (PEM) was tested to establish whether it can contribute further
      information about the patient's medication on admission. MATERIALS AND METHODS:
      This cross-sectional study included patients admitted to an acute medical
      admissions ward. In addition to the ward's usual admission procedure, a clinical
      pharmacist created an extra medication history by carrying out semi-structured
      interviews and obtaining additional information from the patient's GP.
      Information was then obtained from the PEM. A clinical expert panel assessed the
      potential clinical relevance of the discrepancies. RESULTS: Of 67 patients
      admitted, 48 were interviewed. The patients' average age was 71, and they used an
      average of 6.4 medications each. There were 309 prescriptions registered,
      producing 85 errors: the extra medication history highlighted 73 of these errors,
      and the subsequent check of the PEM revealed a further 12 errors. Thirty-three
      patients (69%) were affected by one or more errors, of which the expert panel
      considered six (18%) to be potentially serious. CONCLUSION: Medication errors on
      admission to hospital reduce the quality of treatment and can lead to adverse
      events. The PEM cannot replace the traditional medication history, but the use of
      a PEM and the increased focus on medication histories can contribute to an
      improved hospital stay.

PMID- 16982017
TI  - [Surgical treatment of proximal femoral fracture].
AB  - In Denmark, 11,000 patients with proximal femoral fractures are admitted to
      hospital each year, using 2.2% of the national hospitalisation capacity. The
      patients are generally old and have a high degree of co-morbidities. In Denmark,
      the 30-day mortality rate is 10%, and on an international level, reoperation
      rates of 10-20% are reported. This article reports on current treatment
      stategies, classifications and surgical techniques and presents possible
      guidelines. The use of specialized centres and accelerated clinical programmes in
      Denmark is recommended.

PMID- 16982018
TI  - [Treatment of alcohol withdrawal symptoms with benzodiazepines].

PMID- 16982019
TI  - [Treatment of rheumatoid arthritis with adalimumab. Results from a Cochrane
      review].

PMID- 16982020
TI  - [Surgical treatment of symptomatic hemorrhoids].

PMID- 16982021
TI  - [Incidence of delirium in a geriatric ward of a university hospital].
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of delirium
      based on the CAM scale in a geriatric ward in a university hospital. This paper
      describes the numbers of predisposing and precipitating factors are compared with
      the development of delirium. Finally, we present a discussion about treatment and
      prophylaxis. MATERIALS AND METHODS: Over a period of eight weeks, all newly
      admitted patients were interviewed and scored with CAM. The numbers of
      predisposing and precipitating factors were registered. Finally, the treatment
      was focused upon. RESULTS: 270 patients were admitted, 222 patients were
      interviewed and 48 patients were excluded. The prevalence of delirium was 7%. We
      were unable to find a correlation between risk factors or precipitating factors
      and delirium for this population. CONCLUSION: The prevalence of 7% is a
      satisfying result. There is a discrepancy between diagnosing delirium with CAM
      and the doctors' routine. All patients must be considered as high-risk patients.
      Treatment has not been completely standardised.

PMID- 16982022
TI  - [Cost-effectiveness of clopidogrel vs. aspirin treatment in high-risk acute
      coronary syndrome patients in Denmark].
AB  - INTRODUCTION: The aim of this study was to estimate the cost-effectiveness of
      clopidogrel versus aspirin (ASA) in Denmark in the secondary prevention of
      cardiovascular events in three high-risk CAPRIE populations: (1) patients with a
      history of coronary artery bypass grafting, (2) patients with a history of
      ischemic events and (3) patients with multiple vascular territory involvement.
      Additionally, the cost-effectiveness of clopidogrel versus no treatment in ASA
      intolerant patients was estimated. MATERIALS AND METHODS: Clinical,
      epidemiological and cost data (Danish estimates) were combined in a Markov model.
      Estimates of transition probabilities were derived from post hoc analyses of the
      CAPRIE database. RESULTS: Cost-effectiveness (CE) ratios ranged from 25,445
      Danish kroner per LYG (life year gained) in patients with a history of CABG to
      55,503 Danish kroner per LYG in patients with multiple vascular territory
      involvement. The estimated cost-effectiveness ratio of clopidogrel in ASA
      intolerant patients was significantly lower (3,093 Danish kroner per LYG).
      Sensitivity analyses showed that the order of magnitude of these CE ratios is
      unaffected by changes in model assumptions. CONCLUSION: In a Danish setting,
      clopidogrel may be considered a cost-effective treatment alternative to ASA for
      the secondary prevention of cardiovascular events in high-risk populations.
      Clopidogrel is also an effective and cost-effective treatment for ASA-intolerant
      patients.

PMID- 16982023
TI  - [Should high-energy traumas always result in a trauma team call?].
AB  - BACKGROUND: This study was performed to evaluate the trauma triage system
      currently used by the general hospital of Viborg County, Denmark. According to
      the trauma triage system, an isolated high-energy trauma leads to a trauma team
      call. The aim of the study was to determine whether a high-energy trauma patient
      with no symptoms of injury is a sufficient indication to lead to a trauma team
      call. MATERIALS AND METHODS: The study was based on prospective registration of
      traumatised patients admitted to the hospital during the period from 1 March 2000
      to 28 February 2003. A ROC curve analysis was used to validate the ability of the
      trauma points to predict severe injury by isolated high-energy traumas. RESULTS:
      The study included 514 trauma patients, 304 of whom had suffered high-energy
      traumas. The positive predictive value of a trauma team call was 45% of severe
      injury. Among the subgroup of patients with no immediate symptoms, the positive
      predictive value was 15%. The ROC curve analysis found the optimum cut point to
      be a high-energy trauma with at least one symptom of injury. The sensitivity was
      70% and the specificity 52%. CONCLUSION: The study suggests that a high-energy
      trauma patient showing no symptoms of injury is not a sufficient indication to
      lead to a trauma team call. This has caused a change in the scoring system. A
      trauma team call based on a high-energy trauma now implies that the patient shows
      signs of at least one symptom of injury.

PMID- 16982024
TI  - [Mediastinal parathyroid cystadenoma--a rare cause of primary
      hyperparathyroidism].
AB  - Parathyroid cysts located in the mediastinum are rare. They may be non
      functioning or associated with primary hyperparathyroidism (PHPT). We present a
      patient with persistent PHPT despite previous parathyroid surgery. Parathyroid
      scintigraphy with 99mTc sestamibi showed no focus with radioactivity retention,
      but MRI revealed a large parathyroid cystadenoma in the mediastinum, which was
      successfully removed. In general, MRI is not the first choice for parathyroid
      imaging, but when the adenoma is localized at ectopic sites, MRI is a good
      imaging modality.

PMID- 16982025
TI  - [Aortic coarctation in a teenager presenting as mycotic pseudoaneurysm].
AB  - Since the introduction of surgical treatment for coarctation aortae, presentation
      of the disease with postcoarctation mycotic pseudoaneurysm has become rare. We
      report an 18-year-old male with endarteritis caused by Staphylococcus aureus
      treated with appropriate antibiotics. Later the patient developed an irritative
      cough and problems with swallowing. CT and MRI of the chest demonstrated a
      postcoarctation pseudoaneurysm. After acute surgery with resection of the
      coarctation and pseudoaneurysm and insertion of a tube graft, the patient had an
      uneventful postsurgical course.

PMID- 16982026
TI  - [Picture of the month: rupture of the pectoralis major].

PMID- 16982028
TI  - Molecular characterization and anticoagulant activity of a novel annexin derived
      from the Taenia solium.
AB  - A novel annexin gene was isolated from the Taenia solium cDNA library by
      degenerate PCR. The purified protein was generated by hydrolysis with thrombin in
      glutathione S-transferase (GST) affinity chromatography following expression in
      GST tagged pGEX-5T vector. It shares the common structural features of the
      annexin family and specially possesses two unique fragments between repeating
      domains II and III which do not exist in other annexin family members revealed by
      aligning and homology modeling, hence it was designated as Tso ANXB2 according to
      the new nomenclature of annexins. According to the parasitic behaviors of the
      origin, a series of coagulation assays was performed, indicating that Tso ANXB2
      inhibits extrinsic blood coagulation pathway and platelet aggregation also has
      platelet binding activity. Nevertheless, the mutant protein deleting the
      consensus coagulation-related KGD motif of Tso ANXB2 showed significant
      decreasing platelet binding and anticoagulation activity.

PMID- 16982029
TI  - Kinetics of oligonucleotide hybridization to photolithographically patterned DNA
      arrays.
AB  - The hybridization kinetics of oligonucleotide targets to oligonucleotide probe
      arrays synthesized using photolithographic fabrication methods developed by
      Affymetrix have been measured. Values for the fundamental adsorption parameters,
      k(a), k(d), and K, were determined at both room temperature and 45 degrees C by
      monitoring the hybridization of fluorescently labeled targets to the array. The
      values for these parameters and the adsorbed target density (<or=1 pmol/cm(2) at
      saturation) agree relatively well with published values for arrays fabricated by
      immobilizing intact probes. The isotherms can be fit well with the Sips model, a
      generalization of the Langmuir model that allows for multiple binding energies.
      However, binding to these arrays also displays certain characteristics that may
      result from the close spacing of probes on the array. At high target
      concentrations and 22 degrees C, an "overshoot" is observed, wherein a large
      amount of target binds rapidly and then desorbs to a final plateau. This binding
      mode may be a result of the unique nature of photolithographically patterned
      arrays given that targets initially can bind in lower stability binding modes by
      partially adsorbing to a probe and its neighbor(s), a process that can be viewed
      as a form of competitive hybridization for overlapping sites on a given probe.
      Using the values measured for k(a) and k(d), an analytical model that accounts
      for this behavior is proposed. Alternatively, at 45 degrees C, the adsorption
      approaches an initial plateau, rather than an overshoot, and then undergoes a
      "secondary rise" to a final value. A potential explanation for this phenomenon
      that is compatible with the analysis at lower temperature is offered.

PMID- 16982030
TI  - Plasma membrane-associated endothelial nitric oxide synthase and activity in
      aging rat aortic vascular endothelia markedly decline with age.
AB  - The mechanisms leading to the age-related loss of endothelial nitric oxide (NO)
      and NO-dependent vasodilation remain largely unknown. Freshly isolated
      endothelium from young (6 months) and old (36 months) F344xBrN rats were analyzed
      for endothelial nitric oxide synthase (eNOS) protein, its subcellular
      distribution, and association with regulatory proteins. Results show that both
      vessel ring vasoreactivity and A23187-induced eNOS activity in isolated
      endothelial cells significantly (p < or = 0.05) declined with age. Levels of
      cGMP, a reliable marker for NO bioactivity also declined significantly (p < or =
      0.01). However, no change in overall eNOS protein was evident. Subcellular
      fractionation studies revealed an age-related loss in active, plasma membrane
      bound eNOS relative to eNOS in the Golgi/cytosol of the endothelium. Plasma
      membrane-associated eNOS in aged endothelium was also less complexed with the
      activating proteins Hsp90 and Akt and more associated with to caveolin-1, which
      inhibits eNOS activity. These results suggest that age-dependent loss of NO may
      be partly caused by differences in eNOS subcellular distribution and its
      association with inhibitory proteins.

PMID- 16982032
TI  - gammaepsilon Sub-complex of thermophilic ATP synthase has the ability to bind
      ATP.
AB  - The isolated epsilon subunit of F(1)-ATPase from thermophilic Bacillus PS3
      (TF(1)) binds ATP [Y. Kato-Yamada, M. Yoshida, J. Biol. Chem. 278 (2003) 36013].
      The obvious question is whether the ATP binding concern with the regulation of
      ATP synthase activity or not. If so, the epsilon subunit even in the ATP synthase
      complex should have the ability to bind ATP. To check if the ATP binding to the
      epsilon subunit within the ATP synthase complex may occur, the gammaepsilon sub
      complex of TF(1) was prepared and ATP binding was examined. The results clearly
      showed that the gammaepsilon sub-complex can bind ATP.

PMID- 16982031
TI  - LC-MS/MS based proteomic analysis and functional inference of hypothetical
      proteins in Desulfovibrio vulgaris.
AB  - High efficiency capillary liquid chromatography-tandem mass spectrometry (LC
      MS/MS) was used to examine the proteins extracted from Desulfovibrio vulgaris
      cells across six treatment conditions. While our previous study provided a
      proteomic overview of the cellular metabolism based on proteins with known
      functions [W. Zhang, M.A. Gritsenko, R.J. Moore, D.E. Culley, L. Nie, K.
      Petritis, E.F. Strittmatter, D.G. Camp II, R.D. Smith, F.J. Brockman, A proteomic
      view of the metabolism in Desulfovibrio vulgaris determined by liquid
      chromatography coupled with tandem mass spectrometry, Proteomics 6 (2006) 4286
      4299], this study describes the global detection and functional inference for
      hypothetical D. vulgaris proteins. Using criteria that a given peptide of a
      protein is identified from at least two out of three independent LC-MS/MS
      measurements and that for any protein at least two different peptides are
      identified among the three measurements, 129 open reading frames (ORFs)
      originally annotated as hypothetical proteins were found to encode expressed
      proteins. Functional inference for the conserved hypothetical proteins was
      performed by a combination of several non-homology based methods: genomic context
      analysis, phylogenomic profiling, and analysis of a combination of experimental
      information, including peptide detection in cells grown under specific culture
      conditions and cellular location of the proteins. Using this approach we were
      able to assign possible functions to 20 conserved hypothetical proteins. This
      study demonstrated that a combination of proteomics and bioinformatics
      methodologies can provide verification of the expression of hypothetical proteins
      and improve genome annotation.

PMID- 16982033
TI  - Upon intracellular processing, the C-terminal death domain-containing fragment of
      the p53-inducible PIDD/LRDD protein translocates to the nucleoli and interacts
      with nucleolin.
AB  - The p53-inducible and death domain-containing PIDD/LRDD protein has been
      described as an adaptor protein, which forms large protein complexes with RAIDD,
      another death domain-containing protein, leading to recruitment, and activation
      of the initiator caspase-2, and p53-mediated apoptosis. Here, we describe in
      further detail the proteolytic processing of PIDD/LRDD that occurs in healthy
      cells before induction of apoptosis. We could demonstrate that the C-terminal
      fragment containing the PIDD death domain shuttles into the nucleoli. This
      translocation is mediated by or leads to the interaction of the PIDD death domain
      with nucleolin, a protein important for rRNA processing within nucleoli and
      possibly involved in the DNA damage response. Ectopically expressed LRDD and
      endogenous nucleolin co-localized within the nucleoli, and overexpression of both
      full-length LRDD and the LRDD death domain sensitized cells for UV-induced
      apoptosis. When expressed alone, the PIDD/LRDD death domain tended to form large
      filamentous structures resembling so-called death filaments. The functional
      consequences of the identified PIDD/nucleolin interaction remain to be
      elucidated, but may be related to a recently discovered new role for PIDD in the
      activation of NF-kappaB upon genotoxic stress.

PMID- 16982034
TI  - Mammary radioiodine accumulation due to functional sodium iodide symporter
      expression in a benign fibroadenoma.
AB  - The sodium iodide symporter (NIS) has been characterized to mediate the active
      transport of iodide not only in the thyroid gland but also in various non
      thyroidal tissues, including lactating mammary gland and the majority of breast
      cancers, thereby offering the possibility of diagnostic and therapeutic
      radioiodine application in breast cancer. In this report, we present a 57-year
      old patient with multifocal papillary thyroid carcinoma, who showed focal
      radioiodine accumulation in a lesion in the right breast on a posttherapy (131)I
      scan following radioiodine therapy. CT and MR-mammography showed a focal solid
      lesion in the right breast suggestive of a fibroadenoma, which was confirmed by
      histological examination. Immunostaining of paraffin-embedded tumor tissue
      sections using a human NIS antibody demonstrated NIS-specific immunoreactivity
      confined to epithelial cells of mammary ducts. In conclusion, in a thyroid cancer
      patient we identified a benign fibroadenoma of the breast expressing high levels
      of functionally active NIS protein as underlying cause of focal mammary
      radioiodine accumulation on a posttherapy (131)I scan. These data show for the
      first time that functional NIS expression is not restricted to lactating mammary
      gland and malignant breast tissue, but can also be detected in benign breast
      lesions, such as fibroadenomata of the breast.

PMID- 16982035
TI  - Mitochondrial permeability transition induced by novel pyridothiopyranopyrimidine
      derivatives: potential new antimitochondrial antitumour agents.
AB  - New pyridothiopyranopyrimidine derivatives (PTP1 and PTP2) were synthesised.
      Evaluation of the antiproliferative activity showed a significant capacity of the
      two compounds to inhibit cell growth. Investigation of the mechanism of action
      reveals that PTP1 interferes with the mitochondrial functions by inducing both
      swelling of the mitochondrial matrix and collapse of the electrical potential.
      These phenomena are fully prevented by typical inhibitors of the mitochondrial
      permeability transition, and are accompanied by the release of cytochrome c in
      the cytosol. The estimation of the redox state of thiol groups and glutathione
      suggests that the induction of permeability transition mediated by PTP1 is the
      result of an oxidative stress. The ability of cyclosporin A to prevent the
      antiproliferative effect of PTP1 indicates the induction of mitochondrial
      permeability transition as the molecular event responsible for the inhibition of
      cell growth. PTP1 also induces DNA fragmentation in intact cells. As regards
      PTP2, the presence of the p-toluensulphonamido group makes the lead chromophore
      unable to induce any effect on mitochondria.

PMID- 16982036
TI  - 2',4',6'-Tris(methoxymethoxy) chalcone attenuates hepatic stellate cell
      proliferation by a heme oxygenase-dependent pathway.
AB  - Proliferation of hepatic stellate cells (HSCs) is central for the development of
      fibrosis during liver injury. We have shown previously that butein (3,4,2',4'
      tetrahydroxychalcone) suppresses myofibroblastic differentiation of rat HSCs. Our
      aim in this study was to determine whether a new synthetic chalcone derivative,
      2',4',6'-tris(methoxymethoxy) chalcone (TMMC) inhibits HSC proliferation induced
      by serum- or platelet-derived growth factor (PDGF). TMMC significantly inhibited
      growth factor-induced HSC proliferation. The inhibition of PDGF-induced
      proliferation by TMMC was associated with the phosphatidylinositol 3-kinase-Akt
      p70(S6K) pathways. TMMC induced the expression of heme oxygenase 1 (HO-1) in
      HSCs. Using the chemical inhibitor tin protoporphyrin, we also found that the
      inhibitory action of TMMC on PDGF-induced proliferation is mediated by HO-1.
      Glutathione (GSH) depletion produced by TMMC activated extracellular signal
      regulated kinase (ERK), which led to c-Fos expression and transactivation of
      activator protein 1 (AP-1) and HO-1 gene expression in the HSCs. These results
      demonstrate that TMMC preferentially activates ERK and that this activation leads
      to the transcriptional activation of AP-1 and consequently to HO-1 expression. HO
      1 expression might be responsible for the antiproliferative effect of TMMC on
      HSCs.

PMID- 16982037
TI  - Organization in the descending tracts of the dorsolateral funiculus in the cat.
AB  - Organization of the fibers in the descending tracts of the dorsolateral funiculus
      of the cervical spinal cord was investigated in cats. The spinal cord was
      penetrated with microelectrodes at 400 mum intervals in the medio-lateral
      direction at the c5/c6 and c6/c7 segmental borders. Silicon substrate
      microelectrodes with a linear arrangement of activated iridium contacts were
      used. The stimulus consisted of a 20 ms train of charge balanced biphasic current
      pulses at 330 Hz. The evoked activities from selected forelimb muscles were
      acquired into computer. Only the data points with an activation threshold of less
      than 35 muA were considered in the analysis. Muscle contractions were mostly in
      the form of short twitches. In both spinal segments, an area of high threshold
      was found in the middle of the dorsolateral funiculus. Majority of the muscles
      studied had a dorsal or ventral concentration of activation points. The distal
      muscles were mostly activated in the ventro-lateral aspect of the funiculus,
      while the elbow muscle maps spread to both dorsal and ventral sides. These
      results show a functional organization in both cervical segments studied, with
      overlapping regions between the areas dedicated for each forelimb muscle.

PMID- 16982038
TI  - Psychophysical 'perceptual maps' of heat and pain sensations by direct
      localization of CO2 laser stimuli on the skin.
AB  - Brain activation patterns derived from neurofunctional methods are often
      implicitly regarded as being directly related to subjective perceptual experience
      in an iso- or at least homomorph manner, neglecting the operational differences
      between these two dimensions. This paper (a) introduces a method for assessing
      'perceptual maps' of stimulation patterns presented to the body surface,
      providing a means to parametrically relate neural representation and subjective
      percept, and (b) applies this method to demonstrate the existence of 'somatotopic
      maps' of hot and painful stimulus patterns independent from mechanoceptive co
      activation. Brief (90 ms) CO2 laser pulses were presented in an array of multiple
      stimulation sites on the dorsal forearms (N. radialis area, C7 dermatome) of
      healthy subjects. Perceived locations were indicated with a 3D tracker without
      touching the skin, and (mis-)localizations in distal-proximal direction were
      analyzed. Stimuli were localized with overall mean errors of 22 mm (SD: 16 mm)
      toward the wrist and 24 mm (SD: 18 mm) toward the elbow. Somatotopic
      representation of thermal-nociceptive stimuli could be demonstrated in all
      subjects, independent from mechanoceptive co-activation. The perceptual maps
      revealed striking individual (mis-)localization patterns, many subjects
      exhibiting 'stretched', some 'condensed' somatotopic representations. In
      estimating the mapping parameters from physical to perceptual space linear
      regressions generally provided a good fit (adj. R2>0.80 in 10 out of 12
      subjects). Nonlinear models were advantageous in some subjects only. Our method
      can be useful in assessing inter-individual differences or experimentally induced
      shifts in somatotopic processing.

PMID- 16982040
TI  - Studies on enolization of aldehydo-aldose derivatives.
AB  - Acetylation of the 2,3-O-isopropylidene derivative (1) of D-glyceraldehyde with
      hot acetic anhydride in the presence of sodium acetate give a mixture of (Z)- and
      (E)-enol acetates (2 and 3), together with the acetylated racemic aldehydrol (4)
      of 1. Likewise, the acyclic aldehydo 2,3:4,5-diisopropylidene acetals of D- and L
      arabinose, D-xylose, and D-ribose underwent conversion into enol acetates, with
      the (Z) isomers preponderating, and convertible photochemically into the
      corresponding (E) isomers. Under other conditions of acetylation, the aldehydo
      derivatives were converted into the corresponding aldehydrol diacetates.

PMID- 16982039
TI  - Ablation of NK1 receptor bearing neurons in the nucleus of the solitary tract
      blunts cardiovascular reflexes in awake rats.
AB  - The nucleus of the solitary tract (NTS) receives primary afferents involved in
      cardiovascular regulation. We investigated the role of NK(1)-receptor bearing
      neurons in the NTS on cardiovascular reflexes in awake rats fitted with chronic
      venous and arterial cannulae. These neurons were lesioned selectively with
      saporin conjugated with substance P (SP-SAP, 2 microM, bilateral injections of 20
      nL in the subpostremal NTS, or 200 nL in both the subpostremal and the
      commissural NTS). Before, and 7 and 14 days after injection of SP-SAP, we
      measured changes in blood pressure and heart rate induced by i.v. injection of
      phenylephrine and nitroprusside (baroreceptor reflex), cyanide (arterial
      chemoreceptor reflex), and phenylbiguanide (Bezold-Jarisch reflex). The smaller
      injections with SP-SAP completely abolished NK1 receptor staining in the
      subpostremal NTS. The larger injections abolished NK1 receptor immunoreactivity
      in an area that extended from the commissural NTS to the rostral end of the
      subpostremal NTS. The lesions seemed to affect only a limited number of neurons,
      since neutral red stained sections did not show any obvious reduction in cell
      number. The smaller lesions reduced the gain of baroreflex bradycardia and the
      hypotension induced by phenylbiguanide. The larger lesions completely abolished
      the response to phenylbiguanide, blocked the baroreflex bradycardia induced by
      phenylephrine, severely blunted the baroreflex tachycardia, and blocked the
      bradycardia and reduced the hypertension induced by cyanide. Thus, these
      responses depend critically on NK(1)-receptor bearing neurons in the NTS.

PMID- 16982041
TI  - Neuroprotective effects of arachidonic acid against oxidative stress on rat
      hippocampal slices.
AB  - Arachidonic acid (AA), 5,8,11,14-eicosateraenoic acid is abundant, active and
      necessary in the human body. In the present study, we reported the
      neuroprotective effects and mechanism of arachidonic acid on hippocampal slices
      insulted by glutamate, NaN(3) or H(2)O(2)in vitro. Different types of models of
      brain injury in vitro were developed by 1mM glutamate, 10mM NaN(3) or 2mM
      H(2)O(2). After 30 min of preincubation with arachidonic acid or linoleic acid,
      hippocampal slices were subjected to glutamate, NaN(3) or H(2)O(2), then the
      tissue activities were evaluated by using the 2,3,5-triphenyltetrazolium chloride
      method. Endogenous antioxidant enzymes activities (SOD, GSH-PX and catalase) in
      hippocampal slices were evaluated during the course of incubation. MK886 (5
      microM; a noncompetitive inhibitor of proliferator-activated receptor
      [PPAR]alpha), BADGE (bisphenol A diglycidyl ether; 100 microM; an antagonist of
      PPARgamma) and cycloheximide (CHX; 30 microM; an inhibitor of protein synthesis)
      were tested for their effects on the neuroprotection afforded by arachidonic
      acid. Population spikes were recorded in randomly selected hippocapal slices.
      Arachidonic acid (1-10 microM) dose dependently protected hippocampal slices from
      glutamate and H(2)O(2) injury (P<0.01), and arachidonic acid (10 microM) can
      significantly improve the activities of Cu/Zn-SOD in hippocampal slices after 1h
      incubation. In addition, 10 microM arachidonic acid significantly increased the
      activity of Mn-SOD and catalase, and decreased the activities of Cu/Zn-SOD to
      control value after 3h incubation. These secondary changes of SOD during
      incubation can be reversed by indomethacine (10 microM; a nonspecific
      cyclooxygenase inhibitor) or AA 861 (20 microM; a 5-lipoxygenase inhibitor). Its
      neuroprotective effect was completely abolished by BADGE and CHX. These
      observations reveal that arachidonic acid can defense against oxidative stress by
      boosting the internal antioxidant system of hippocampal slices. Its
      neuroprotective effect may be mainly mediated by the activation of PPARgamma and
      synthesis of new protein in tissue.

PMID- 16982043
TI  - Novel missense mutations in the first Chinese patient with very-long-chain acyl
      CoA dehydrogenase deficiency.

PMID- 16982042
TI  - Effects of phospholipase A2 on the lysosomal ion permeability and osmotic
      sensitivity.
AB  - In this study, we investigated the mechanism of PLA(2)-induced lysosomal
      destabilization. Through the measurements of lysosomal beta-hexosaminidase free
      activity, their membrane potential, the intra-lysosomal pH and the lysosomal
      latency loss in hypotonic sucrose medium, we established that PLA(2) could
      increase the lysosomal membrane permeability to both potassium ions and protons.
      The enzyme could also enhance the organelle osmotic sensitivity. The increases in
      the lysosomal ion permeability promoted influx of potassium ions into the
      lysosomes via K(+)/H(+) exchange. The resulted osmotic imbalance across the
      lysosomal membranes osmotically destabilized the lysosomes. In addition, the
      enhancement of the lysosomal osmotic sensitivity caused the lysosomes to become
      more liable to destabilization in the osmotic stress. The results explain how
      PLA(2) destabilized the lysosomes.

PMID- 16982044
TI  - Judgments of associative memory.
AB  - Judgments of associative memory (JAM) were indexed by ratings given to pairs of
      cue and response words. The normed probabilities, p(response|cue), were obtained
      from free association norms. The ratings were linearly related to the
      probabilities. The JAM functions were characterized by high intercepts (
      approximately 50 on a 100 point scale) and shallow slopes (<0.5). The JAM
      function generalized across materials and method of rating. The function was not
      affected by expectancies or semantic similarity. Attempts to alter the function
      by making alternative responses more available were unsuccessful. A computer
      simulation model (MINERVA 2) exhibited the linear JAM function and successfully
      accounted for more complex phenomena (like the joint influence of forward and
      backward associative strengths on ratings). The shallow JAM slope appears to
      result from a fundamental lack of discrimination among associative strengths. The
      high intercept appears to result partly from an independent post-mnemonic source
      of bias producing over-estimation of association.

PMID- 16982045
TI  - A wavelet-based data pre-processing analysis approach in mass spectrometry.
AB  - Recently, mass spectrometry analysis has a become an effective and rapid approach
      in detecting early-stage cancer. To identify proteomic patterns in serum to
      discriminate cancer patients from normal individuals, machine-learning methods,
      such as feature selection and classification, have already been involved in the
      analysis of mass spectrometry (MS) data with some success. However, the
      performance of existing machine learning methods for MS data analysis still needs
      improving. The study in this paper proposes a wavelet-based pre-processing
      approach to MS data analysis. The approach applies wavelet-based transforms to MS
      data with the aim of de-noising the data that are potentially contaminated in
      acquisition. The effects of the selection of wavelet function and decomposition
      level on the de-noising performance have also been investigated in this study.
      Our comparative experimental results demonstrate that the proposed de-noising pre
      processing approach has potentials to remove possible noise embedded in MS data,
      which can lead to improved performance for existing machine learning methods in
      cancer detection.

PMID- 16982046
TI  - Chondroitin acts in the guidance of gonadal distal tip cells in C. elegans.
AB  - In Caenorhabditis elegans hermaphrodites, the U-shaped gonad arms are formed by
      directed migration of the gonadal distal tip cells (DTCs). The stereotyped
      pattern of DTC migration is carefully controlled by extracellular and cell
      surface molecules during larval development. Here we report that two proteins,
      SQV-5 (chondroitin synthase) and its cofactor MIG-22 (chondroitin polymerizing
      factor), are required for chondroitin biosynthesis and are essential for the
      dorsally guided migration of DTCs. We found that MIG-22 is expressed in migrating
      DTCs, hypodermal seam cells, developing vulva and oocytes. The expression of SQV
      5 or MIG-22 in both DTCs and hypodermis rescued the DTC migration defects of the
      relevant mutants more efficiently than when they were expressed in either single
      tissue. Furthermore, the expression of SQV-5 by the mig-22 promoter significantly
      rescued sqv-5 mutants, implying that these two proteins act in the same tissues
      and that chondroitin proteoglycans produced in both of these tissues are required
      for DTC migration. The DTC migration defects caused by sqv-5 or mig-22 mutations
      were partially suppressed in the anterior and enhanced in the posterior DTCs in
      unc-6, unc-5 or unc-40 mutant backgrounds, suggesting that chondroitin
      proteoglycans play roles in the UNC-6/netrin-dependent guidance of DTCs.

PMID- 16982047
TI  - FGF signal transduction and the regulation of Cdx gene expression.
AB  - Cdx homeodomain transcription factors play important roles in the development of
      the vertebrate body axis and gut epithelium. Signaling involving FGF, wnt and
      retinoic acid ligands has been implicated in the regulation of individual Cdx
      genes. In this study we examine the requirement for FGF-dependent signal
      transduction pathways in the regulation of Cdx gene expression. In the amphibian
      Xenopus laevis the earliest expression of Cdx1, Cdx2 and Cdx4 is within the
      developing mesoderm. We show that a functional FGF signaling pathway is required
      for the normal expression of all three amphibian Cdx genes during gastrula
      stages. We show that FGF stimulation activates signaling through both the MAP
      kinase pathway and the PI-3 kinase pathway in Xenopus tissue explants. However,
      our analysis of these pathways in gastrula stage embryos indicates that the MAP
      kinase pathway is required for Cdx gene expression, whereas the PI-3 kinase
      pathway is not. We show that FGF and wnt signaling can interact in the regulation
      of Cdx genes and during gastrula stages the normal expression of the Cdx genes
      requires the activity of both pathways. Furthermore, we show that wnt mediated
      Cdx regulation is independent of the MAP kinase pathway.

PMID- 16982048
TI  - The role of gap junctions in Caenorhabditis elegans oocyte maturation and
      fertilization.
AB  - We have investigated the role of gap junctions in Caenorhabditis elegans oocyte
      maturation and fertilization. Gap junctions are observed between oocytes and the
      surrounding ovarian sheath cells in wild-type gonads. The sheath transcription
      factor CEH-18 is required to negatively regulate oocyte maturation, mitogen
      activated protein kinase (MAPK) activation, and ovulation. Transmission electron
      microscopy (TEM) indicates that sheath/oocyte gap junctions are rare or absent in
      ceh-18(mg57) null mutant gonads. To test the hypothesis that gap junctions
      negatively regulate oocyte maturation, we performed an RNAi screen of innexin
      genes, which encode channel-forming proteins. Here we show that INX-14 and INX-22
      are required in the female germ line to inhibit oocyte maturation, MAPK
      activation, and ovulation. Genetic analysis and TEM are consistent with INX-14
      and INX-22 being components of sheath/oocyte gap junctions. Our results support
      the hypothesis that gap junctions maintain oocytes in meiotic prophase I when
      sperm are absent. We also implicate these channels in regulating sheath cell
      contractile activity and sperm recruitment to the spermatheca, the site of sperm
      storage and fertilization. Together with previous studies, our results help
      establish the C. elegans gonad as a model system for investigating the molecular
      mechanism(s) by which gap junctions regulate meiosis and fertilization.

PMID- 16982050
TI  - Zebrafish cypher is important for somite formation and heart development.
AB  - Mammalian CYPHER (Oracle, KIA0613), a member of the PDZ-LIM family of proteins
      (Enigma/LMP-1, ENH, ZASP/Cypher, RIL, ALP, and CLP-36), has been associated with
      cardiac and muscular myopathies. Targeted deletion of Cypher in mice is neonatal
      lethal possibly caused by myopathies. To further investigate the role of cypher
      in development, we have cloned the zebrafish orthologue. We present here the
      gene, domain structure, and expression pattern of zebrafish cypher during
      development. Cypher was not present as a maternal mRNA and was absent during
      early development. Cypher mRNA was first detected at the 3-somite stage in
      adaxial somites, and as somites matured, cypher expression gradually enveloped
      the whole somite. Later, cypher expression was also found in the heart, in head
      and jaw musculature, and in the brain. We further identified 13 alternative
      spliced forms of cypher from zebrafish heart and skeletal muscle tissue, among
      them a very short form containing the PDZ domain but lacking the ZM (ZASP-like)
      motif and the LIM domains. Targeted gene knock-down experiments using cypher
      antisense morpholinos led to severe defects, including truncation of the embryo,
      deformation of somites, dilatation of the pericardium, and thinning of the
      ventricular wall. The phenotype could be rescued by a cypher form, which contains
      the PDZ domain and the ZM motif, but lacks all three LIM domains. These findings
      indicate that a PDZ domain protein is important for normal somite formation and
      in normal heart development. Treatment of zebrafish embryos with cyclopamine,
      which disrupts hedgehog signaling, abolished cypher expression in 9 somite and 15
      somite stage embryos. Taken together, our data suggest that cypher may play a
      role downstream of sonic hedgehog, in a late stage of somite development, when
      slow muscle fibers differentiate and migrate from the adaxial cells.

PMID- 16982049
TI  - GLP-1: a novel zinc finger protein required in somatic cells of the gonad for
      germ cell development.
AB  - Mouse gonadal development is regulated by a variety of transcription factors.
      Here we report the identification and characterization of a novel nuclear zinc
      finger protein called GATA like protein-1 (GLP-1), which is expressed at high
      levels in the somatic cells of the developing gonads, including Leydig cells in
      the testes and granulosa cells in the ovaries. Biochemical analysis of GLP-1
      shows that it acts as a transcriptional repressor of GATA factor function. To
      determine the necessity of GLP-1 in gonadal development, a null allele in mice
      was generated by replacing all of the coding exons with the bacterial lacZ gene.
      GLP-1(lacZ) null mice are viable with no detectable defects in visceral organ
      development; however, both males and females are completely infertile. Loss of
      GLP-1 leads to defective sperm development in males with a marked reduction in
      mature spermatids observed as early as postnatal week 1. In females, loss of GLP
      1 leads to a severe block in germ cell development as early as E17.5. Together,
      these data identify GLP-1 as a critical nuclear repressor in somatic cells of the
      gonad that is required for germ cell development, and highlight the importance of
      somatic-germ cell interactions in the regulation of this critical process.

PMID- 16982051
TI  - Effects of postconditioning of adenosine and acetylcholine on the ischemic
      isolated rat ventricular myocytes.
AB  - In this study, protective effects of adenosine and acetylcholine-induced
      postconditioning were investigated on the contractile function of the ischemic
      isolated rat ventricular myocytes. A video-based edge-detection system was used
      to monitor single ventricular myocytes contraction. Adenosine and acetylcholine
      were administrated for 6 min before ischemia as preconditioning, or 15 min after
      ischemia as postconditioning. Adenosine and acetylcholine receptor antagonists
      and mitoKATP inhibitor were used to analyze pathways underlying the effects on
      postconditioning. RESULTS: (1) The peak shortening of ischemic heart cells was
      improved by both adenosine and acetylcholine during preconditioning (84.72+/
      5.34% and 68.61+/-8.10% vs. control: 8.43+/-5.35% of the pre-ischemia value), as
      well as postconditioning (76.47+/-7.87% and 57.48+/-6.97% vs. control: 8.43+/
      5.35% of the pre-ischemia value) and the effects of preconditioning and
      postconditioning were comparable. More datum in the normal text. (2) Observed
      effects of adenosine and acetylcholine postconditioning were missing in the
      presence of adenosine A1 receptor and muscarinic M2 receptor antagonists,
      respectively. (3) Adenosine and acetylcholine-induced postconditioning was also
      blocked by mitoKATP antagonist. These results suggest that both adenosine and
      acetylcholine protect the contractile function of ischemic heart cells to a
      similar extent during preconditioning and postconditioning. The postconditioning
      of adenosine and acetylcholine is relative to the adenosine A1 and muscarinic M2
      receptors, respectively. MitoKATP is implicated in the postconditioning of both
      acetylcholine and adenosine.

PMID- 16982052
TI  - Allogeneic mesoangioblasts give rise to alpha-sarcoglycan expressing fibers when
      transplanted into dystrophic mice.
AB  - Cell therapy for muscular dystrophy involves transplantation of either
      genetically modified autologous cells or normal donor cells that will be rejected
      unless the host is adequately immune suppressed. The extent of the immune
      response appears to be mitigated in this case of stem cells, by immune
      suppressive and tolerogenic molecules that they release. We previously reported
      significant morphological and functional amelioration of a mouse model of limb
      girdle muscular dystrophy by transplantation of mesoangioblasts. These are vessel
      associated stem cells that can be propagated in vitro and differentiate into
      several types of mesoderm including skeletal muscle. In these experiments, both
      donor cells and host were syngeneic (C57Bl/6J) and thus possible immune reaction
      to the donor cells could not be appreciated. To address this question, we
      transplanted H2-mismatched mesoangioblasts (BalbC) in the same dystrophic mice,
      and in addition, we treated the host with different pharmacological drugs
      (rapamycin, IL-10 or both). The results showed that donor cells give rise to
      fibers that express the mutated gene product (alpha-sarcoglycan) even in the
      absence of immune suppression; however, the combined action of rapamycin and IL
      10 increases the number of alpha-sarcoglycan expressing fibers while reducing the
      levels of inflammatory cytokines. These results indicate that transplantation of
      mesoangioblasts into immunologically unrelated host leads to long-term survival
      of donor cells and this may be further enhanced by appropriate protocols of
      immune modulation, thus setting the stage for experimentation in large animals
      and in patients.

PMID- 16982053
TI  - Connexin 26 expression prevents down-regulation of barrier and fence functions of
      tight junctions by Na+/K+-ATPase inhibitor ouabain in human airway epithelial
      cell line Calu-3.
AB  - Gap junctions are considered to play a crucial role in differentiation of
      epithelial cells and to be associated with tight junction proteins. In this
      study, to investigate the role of gap junctions in regulation of the barrier
      function and fence function on the tight junctions, we introduced the Cx26 gene
      into human airway epithelial cell line Clau-3 and used a disruption model of
      tight junctions employing the Na(+)/K(+)-ATPase inhibitor ouabain. In parental
      Calu-3 cells, gap junction proteins Cx32 and Cx43, but not Cx26, and tight
      junction proteins occludin, JAM-1, ZO-1, claudin-1, -2, -3, -4, -5, -6, -7, -8, 
      9, and -14 were detected by RT-PCR. The barrier function and fence function of
      tight junctions were well maintained, whereas the GJIC was low level. Treatment
      with ouabain caused disruption of the barrier function and fence function of
      tight junctions together with down-regulation of occludin, JAM-1, claudin-2, and 
      4 and up-regulation of ZO-1 and claudin-14. In Cx26 transfectants, Cx26 protein
      was detected by Western blotting and immunocytochemistry, and many gap junction
      plaques were observed with well-developed tight junction strands. Expression of
      claudin-14 was significantly increased in Cx26 transfectants compared to parental
      cells, and in some cells, Cx26 was co-localized with claudin-14. Interestingly,
      transfection with Cx26 prevented disruption of both functions of tight junctions
      by treatment with ouabain without changes in the tight junction proteins.
      Pretreatment with the GJIC blockers 18beta-glycyrrhetinic acid and oleamide did
      not affect the changes induced by Cx26 transfection. These results suggest that
      Cx26 expression, but not the mediated intercellular communication, may regulate
      tight junction barrier and fence functions in human airway epithelial cell line
      Calu-3.

PMID- 16982054
TI  - Hypoxia-induced mitogenic factor enhances angiogenesis by promoting proliferation
      and migration of endothelial cells.
AB  - Our previous studies have indicated that hypoxia-induced mitogenic factor (HIMF)
      has angiogenic properties in an in vivo matrigel plug model and HIMF upregulates
      expression of vascular endothelial growth factor (VEGF) in mouse lungs and
      cultured lung epithelial cells. However, whether HIMF exerts angiogenic effects
      through modulating endothelial cell function remains unknown. In this study,
      mouse aortic rings cultured with recombinant HIMF protein resulted in enhanced
      vascular sprouting and increased endothelial cell spreading as confirmed by Dil
      Ac-LDL uptake, von Willebrand factor and CD31 staining. In cultured mouse
      endothelial cell line SVEC 4-10, HIMF dose-dependently enhanced cell
      proliferation, in vitro migration and tubulogenesis, which was not attenuated by
      SU1498, a VEGFR2/Flk-1 receptor tyrosine kinase inhibitor. Moreover, HIMF
      stimulation resulted in phosphorylation of Akt, p38 and ERK1/2 kinases in SVEC 4
      10 cells. Treatment of mouse aortic rings and SVEC 4-10 cells with LY294002, but
      not SB203580, PD098059 or U0126, abolished HIMF-induced vascular sprouting and
      angiogenic responses. In addition, transfection of a dominant-negative mutant of
      phosphatidylinositol 3-kinase (PI-3K), Deltap85, blocked HIMF-induced
      phosphorylation of Akt, endothelial activation and tubulogenesis. These results
      indicate that HIMF enhances angiogenesis by promoting proliferation and migration
      of endothelial cells via activation of the PI-3K/Akt pathways.

PMID- 16982055
TI  - Exploring ego-integrity in old adults: a Q-methodology study.
AB  - BACKGROUND: Achieving ego-integrity involves fully accepting oneself and is
      important in quality of later life, but the concept of ego-integrity in old
      adults has not yet been well articulated in nursing practice. OBJECTIVES: This
      study aimed to elucidate the concept of ego-integrity in late adulthood in terms
      of the range of meanings this concept embraces within contemporary Korean
      society. DESIGN: Q-methodology was applied, which represents a method for
      measuring subjectivity. SETTINGS: The study was performed in a community setting
      in the Republic of Korea. PARTICIPANTS: The participants were 26 old adults, aged
      65-70 years, living in the community in Korea. Two inclusion criteria were
      applied: (1) the participants had to be literate and competent to ensure that
      they were able to sort the cards stating the Q-samples in a forced distributive
      manner, and (2) the participants were regarded by researchers as having achieved
      ego-integrity in late adulthood as described in the literature. METHODS: Data
      obtained from June 2004 to December 2004 from a sample of 26 older adults were
      analyzed by PCQ software (a factor analysis program for the Q-technique) to
      delineate the factors of ego-integrity in late adulthood. RESULTS: A four-factor
      solutions for the study subjects indicates that there were differences in the
      frames of reference in achieving ego-integrity in late adulthood. The frames of
      reference of the four factors were: (1) a satisfactory connection between the
      generations, (2) enjoying a peaceful life, (3) peace through acceptance, and (4)
      achieving a praiseworthy life in spite of adversity. CONCLUSION: The projected
      property of ego-integrity in late adulthood is closely related to cultural and
      psycho-social environmental influences throughout the life span. Culturally
      sensitive life-reviews methods need to be developed to intervene in the specific
      ways that individual older adults achieve their own ego-integrity throughout
      their life experiences.

PMID- 16982056
TI  - The reliability and validity of the Polish version of the Breastfeeding Self
      Efficacy Scale-Short Form: translation and psychometric assessment.
AB  - BACKGROUND: The majority of women discontinue breastfeeding before the
      recommended 6 months postpartum. If health professionals are to improve low
      breastfeeding duration and exclusivity rates, they need to reliably assess high
      risk women and identify predisposing factors that are amenable to intervention.
      One possible modifiable variable is breastfeeding confidence. The Breastfeeding
      Self-Efficacy Scale Short Form (BSES-SF) is a 14-item measure designed to assess
      a mother's confidence in her ability to breastfeed her baby. OBJECTIVES: To
      translate the BSES-SF into Polish and assess its psychometric properties among
      breastfeeding mothers. DESIGN: Methodological study. SETTING: Five hospitals in
      Lodz Poland. PARTICIPANTS: Using convenience sampling, 105 in-hospital
      breastfeeding mothers were recruited. METHODS: Following back-translation
      procedures, mothers completed questionnaires in-hospital and at 8 and 16 weeks
      postpartum. RESULTS: The Cronbach's alpha coefficient for internal consistency
      was 0.89. In-hospital BSES-SF scores significantly predicted breastfeeding
      duration and exclusivity at 8 and 16 weeks postpartum. Demographic response
      patterns suggested the BSES-SF is a unique tool to identify breastfeeding mothers
      at risk of prematurely discontinuing. CONCLUSIONS: This study provides evidence
      that the translated version of the BSES-SF may be a valid and reliable measure of
      breastfeeding self-efficacy among a sample of mothers in Lodz Poland.

PMID- 16982057
TI  - Changes in health-related quality of life following percutaneous coronary
      intervention: a longitudinal study.
AB  - BACKGROUND: Coronary artery disease (CAD) is a major cause of mortality and
      morbidity in developed countries. The percutaneous coronary intervention (PCI) is
      a frequently used treatment for CAD. In order to manage the disease more
      effectively and to promote the health-related quality of life (HRQoL) of these
      patients, understanding the current status of HRQoL before and after PCI
      procedure is essential. OBJECTIVES: This study was to examine the changes of
      HRQoL from before PCI to the first 3 months after PCI on Hong Kong Chinese.
      DESIGN: A longitudinal, one-group observational design was used. SETTING: Data
      collected from cardiac patients admitted into a regional public hospital at Hong
      Kong Island for PCI. PARTICIPANTS: Between August 2003 and February 2004, all
      patients admitted for non-emergency PCI at the study site and met the inclusion
      criteria were invited to take part in the study. Seventy-eight out of 85 eligible
      patients agreed to participate. However, 13 patients dropped out during data
      collection period. METHODS: HRQoL data using the Medical Outcomes Study 36-Item
      Short Form 36 (SF-36) and Seattle Angina Questionnaire (SAQ) were collected
      before PCI, 1 and 3 months after PCI. RESULTS: Sixty-five patents completed the
      study. All domains in SF-36 and SAQ improved at 1 month but the improvements did
      not continue in all domains at 3 months. The HRQoL measured by SF-36 improved
      significantly over time (p<0.05) for six out of the eight domains. Scores of all
      domains of SF-36 improved at 3 months when compared with baseline. Moreover, all
      five domains of SAQ changed significantly over time (p<0.05); however, the score
      of angina stability at the third month was lower than that at baseline.
      CONCLUSIONS: The results of this study quantify the benefits of PCI procedure on
      HRQoL of patients. Although PCI improved the HRQoL 1 month after PCI, the effect
      did not last long. Nursing interventions are needed to maintain and further
      enhance the HRQoL of these patients and the interventions should be introduced
      immediately post-PCI.

PMID- 16982058
TI  - Autologous bone-marrow mononuclear cell implantation in patients with severe
      lower limb ischaemia: a comparison of using blood cell separator and Ficoll
      density gradient centrifugation.
AB  - Different studies have provided evidence that implantation of bone-marrow
      mononuclear cells (BM-MNC) into ischaemic limbs can improve tissue
      vascularization. Based on these results we performed a pilot study in patients
      with critical lower limb ischaemia to assess efficacy and safety of implantation
      of autologous BM-MNC. The amount and efficacy of BM-MNC purified either by an
      automated method or by a manual procedure were compared. Twelve patients with
      severe unilateral lower limb ischaemia were entered into this study. They were
      randomly assigned to be injected with BM-MNC sorted on a blood cell separator or
      isolated by density gradient on Ficoll-Hypaque. BM-MNC were implanted into the
      ischaemic legs. Patients were monitored with resting ankle-brachial pressure
      index (ABI), arterial oxygen saturation (SaO(2)), pain-free walking time and rest
      pain scale evaluation. The automated and manual methods used for mononuclear cell
      separation gave results not significantly different. Monitored variables improved
      in both groups. Improvement of ischaemic condition persisted during 24 weeks
      follow-up. Limb salvage was achieved in five cases. Our results indicate that BM
      MNC implantation into ischaemic limbs is a practical, safe and effective method
      that may significantly contribute to the management of patients with limb
      ischaemia. The Ficoll method is a simple and effective procedure for BM-MNC
      concentration that may be useful, mainly in hospitals without sophisticated
      facilities.

PMID- 16982059
TI  - The relationship between oxidized LDL and other cardiovascular risk factors and
      subclinical CVD in different ethnic groups: the Multi-Ethnic Study of
      Atherosclerosis (MESA).
AB  - Several groups have demonstrated an association between established CHD and
      elevated oxidized LDL (oxLDL). The relation with cardiovascular risk factors and
      subclinical CVD is less clear. Therefore, we examined this association in the
      Multi-Ethnic Study of Atherosclerosis cohort: 879 persons without CHD, all non
      statin users, examined cross-sectionally. oxLDL was measured with a monoclonal
      antibody 4E6-based ELISA. The presence of subclinical CVD was defined as plaque
      occurrence in carotid arteries with > or = 25 stenosis, ankle-brachial blood
      pressure index (ABI) < 0.9 and coronary calcification based on Agatston calcium
      score > or = 200. In a multivariate model, dyslipidemia (adverse levels of
      cholesterol, HDL-cholesterol, triglycerides), inflammation (elevated fibrinogen),
      gender (male), ethnicity (Black), and current smoking explained the most
      variation in oxLDL (model R2=0.41). In bivariate analyses, persons with
      subclinical CVD had higher levels of oxLDL (1.22 mg/dl versus 0.95 mg/dl;
      P=0.0002). Adjustment for risk factor correlates attenuated associations with
      subclinical CVD (P=0.026). In conclusion, oxLDL is associated with subclinical
      CVD by its relationship with many cardiovascular risk factors.

PMID- 16982060
TI  - Toll-like receptor 4 signalling is neither sufficient nor required for oxidised
      phospholipid mediated induction of interleukin-8 expression.
AB  - OBJECTIVE: Toll-like receptor (TLR)-4 signalling has been shown to accelerate
      atherosclerosis. As oxidised phospholipids are present in atherosclerotic plaque
      and have been shown to modulate TLR4 signalling, we investigated the role of
      oxidised 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (OxPAPC) in the
      regulation of TLR 1, 2, 4 and 6 signalling. METHODS AND RESULTS: Unlike
      established TLR agonists, OxPAPC did not induce NF-kappaB-dependent gene
      expression in monocytic THP-1 cells, human aortic endothelial cells or TLR
      deficient HEK-293 cells transfected with TLRs 1, 2, 4 or 6. OxPAPC induction of
      IL-8 was not blocked by the TLR4 specific antagonist Rhodobacter sphaeroides LPS
      in human aortic endothelial cells, though OxPAPC potently inhibited TLR4 mediated
      IL-8 induction in these cells. OxPAPC upregulated IL-8 production in TLR4
      deficient HEK-293 cells and this was not increased following TLR4 overexpression.
      Lipids extracted from carotid atherectomy samples did not stimulate TLR 1, 2, 4
      or 6 signalling in a HEK-293 transfection assay. CONCLUSIONS: TLR4 signalling
      does not contribute to OxPAPC induced IL-8 expression in human epithelial HEK
      293, monocytic THP-1 or aortic endothelial cells. As lipids extracted from
      diseased human artery also induced no TLR signalling, it is likely that the TLR
      activating materials contributing to atherosclerosis are not of endogenous lipid
      origin.

PMID- 16982062
TI  - Diet-induced hyperhomocysteinemia does not lead to large gene-expression
      differences in rat aorta.

PMID- 16982061
TI  - Comparison of the pro-inflammatory potential of monocytes from healthy adults and
      those with peripheral arterial disease using an in vitro culture model.
AB  - We adapted a monocyte:endothelial cell co-culture model to investigate the pro
      inflammatory potential of monocytes from patients with peripheral arterial
      disease (PAD). Isolated monocytes were cultured with human umbilical vein
      endothelial cells (HUVEC) for 24h, after which the ability of the HUVEC to
      recruit flowing neutrophils was tested. Development of a usable protocol required
      comparisons of primary HUVEC with cells that had been passaged and/or frozen and
      thawed, evaluation of optimal culture media and comparison of monocytes from
      freshly drawn and stored blood. We found, for instance, that expansion of HUVEC
      was assisted by inclusion of hydrocortisone, but this agent was withdrawn before
      the test phase because it reduced responses of HUVEC. Using the optimal practical
      protocol, we found great variation in the ability of monocytes from different
      donors to cause neutrophil adhesion. Slightly more ( approximately 20%) monocytes
      from patients with PAD adhered to HUVEC than monocytes from healthy controls, and
      the monocytes from PAD patients induced approximately 70% greater subsequent
      adhesion of neutrophils. Thus, we developed a functional model of inflammatory
      potential usable in clinically-related studies and found that patients with PAD
      had circulating monocytes with greater than normal ability to activate
      endothelial cells.

PMID- 16982063
TI  - Quality evaluation of Radix Astragali through a simultaneous determination of six
      major active isoflavonoids and four main saponins by high-performance liquid
      chromatography coupled with diode array and evaporative light scattering
      detectors.
AB  - A method, high-performance liquid chromatography coupled with diode array and
      evaporative light scattering detectors (HPLC-DAD-ELSD), was developed to evaluate
      the quality of Radix Astragali through a simultaneous determination of six major
      active isoflavonoids and four main saponins. The wavelength at 280 nm was chosen
      to determine six isoflavonoids: calycosin-7-O-beta-D-glucoside (1), ononin (2),
      (6alphaR, 11alphaR)-9,10-dimethoxypterocarpan-3-O-beta-D-glucoside (3), (3R)-2'
      hydroxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucoside (4), calycosin (5), and
      formononetin (6); and ELSD connected after DAD was employed to determine four
      saponins: astragaloside IV (7), astragaloside II (8), astragaloside I (9), and
      acetylastragaloside I (10). This assay was fully validated with respect to
      precision, repeatability and accuracy. The proposed method was successfully
      applied to quantify the ten components in eleven samples from different
      localities in China; significant variations were demonstrated in the content of
      these compounds in the samples from different areas. This simple, rapid, low-cost
      and reliable HPLC-DAD-ELSD method is suitable for routine quantitative analysis
      and quality control of traditional Chinese medicines (TCMs) consisting of
      bioactive multi-components with different structures such as Radix Astragali.

PMID- 16982064
TI  - Ultrasound-assisted pressurized solvent extraction for aliphatic and polycyclic
      aromatic hydrocarbons from soils.
AB  - In the present work the efficiency of extraction of aliphatic diesel range
      organics (DROs) and polycyclic aromatic hydrocarbons (PAHs) from soil was
      assessed by using dynamic modes of pressurized solvent extraction (PSE), and
      ultrasound-assisted pressurized solvent extraction (US-PSE). Optimization studies
      were carried out using a blank soil (Non-Polluted Soil#1, CLN-1, RTC) and a real
      soil which was previously spiked with the analyte mixture and aged for 90 days. A
      laboratory-made manifold with controlled temperature and pressure was used to
      carry out the leaching processes. The extraction cell was inserted into an oven
      for PSE and into an ultrasound bath for US-PSE. The following variables were
      studied in each case, keeping the pressure at about 1800 psi: extraction
      temperature, time of static and dynamic extraction and solvent flow rate. In
      addition, the time of ultrasound application was also studied in US-PSE. For PSE
      with dichloromethane (DCM) the recoveries were about 90-95% for both the families
      of analytes, using extraction times of 20 min. Analyte extraction was
      quantitative by using US-PSE with DCM for 10 min. In all cases, after the
      extraction process, the analytes were determined by GC-MS. Application of the
      method to a natural contaminated sample suggests that either the extraction time
      used in US-PSE should be increased to 20 min or the solvent (DCM) should be
      replaced by a mixture of DCM:acetone (1:1), to reach comparability with Soxhlet
      extraction.

PMID- 16982065
TI  - Biological fingerprinting analysis of the interactome of a kinase inhibitor in
      human plasma by a chemiproteomic approach.
AB  - In this study, a gel free chemiproteomic method based on chromatography was
      developed and applied for the biological fingerprinting analysis of complex
      biological system. p-Aminobenzamidine (ABA), an inhibitor of trypsin-like serine
      proteases, was immobilized for characterizing their interacting proteins in human
      plasma. By the proteomic analysis method, 214 proteins were identified with
      obvious affinity to the immobilized ABA. By searching the sequences of above
      proteins with consensus patterns of the two active sites, seven proteins belong
      to trypsin-like serine protease group were found. Based on the Gene Ontology
      annotation, the identified trypsin-like serine proteases have the function of
      catalytic activity and calcium ion binding, and are mainly involved in the
      biological process of blood coagulation. Eight more other proteins related to
      calcium ion binding and blood coagulation were found. Nearly all of these
      proteins cannot be identified by directly analyzing the plasma sample
      demonstrating the chemiproteomics a useful approach to characterize interacting
      proteins in the low abundance range.

PMID- 16982066
TI  - The regulation of heat shock protein expression: how, when and where.

PMID- 16982067
TI  - Minimalist representations and the importance of nearest neighbor effects in
      protein folding simulations.
AB  - In order to investigate the level of representation required to simulate folding
      and predict structure, we test the ability of a variety of reduced
      representations to identify native states in decoy libraries and to recover the
      native structure given the advanced knowledge of the very broad native
      Ramachandran basin assignments. Simplifications include the removal of the entire
      side-chain or the retention of only the Cbeta atoms. Scoring functions are
      derived from an all-atom statistical potential that distinguishes between atoms
      and different residue types. Structures are obtained by minimizing the scoring
      function with a computationally rapid simulated annealing algorithm. Results are
      compared for simulations in which backbone conformations are sampled from a
      Protein Data Bank-based backbone rotamer library generated by either ignoring or
      including a dependence on the identity and conformation of the neighboring
      residues. Only when the Cbeta atoms and nearest neighbor effects are included do
      the lowest energy structures generally fall within 4 A of the native backbone
      root-mean square deviation (RMSD), despite the initial configuration being highly
      expanded with an average RMSD > or = 10 A. The side-chains are reinserted into
      the Cbeta models with minimal steric clash. Therefore, the detailed, all-atom
      information lost in descending to a Cbeta-level representation is recaptured to a
      large measure using backbone dihedral angle sampling that includes nearest
      neighbor effects and an appropriate scoring function.

PMID- 16982068
TI  - Bacteriophage T4 capsid: a unique platform for efficient surface assembly of
      macromolecular complexes.
AB  - We report the first description of a macromolecular complex display system using
      bacteriophage T4. Decorated with two dispensable outer capsid proteins, Hoc (155
      copies) and Soc (810 copies), the 120 nm x 86 nm T4 capsid particle offers a
      unique binding site-rich platform for surface assembly of hetero-oligomeric
      complexes. To display the 710 kDa anthrax toxin complex, two bipartite functional
      fusion proteins, LF-Hoc and LFn-Soc, were constructed. Using a defined in vitro
      binding system, sequential assembly was performed by first attaching LF-Hoc
      and/or LFn-Soc to hoc-soc- phage, saturating the Hoc and Soc binding sites.
      Trypsin-nicked PA63 was then assembled into heptamers through specific
      interaction with the capsid-exposed LFn domain. EF was then attached to the
      unoccupied sites of PA63 heptamers, completing the assembly of the tripartite
      anthrax toxin. Negative electron microscopy showed decoration of each capsid with
      a layer of heptameric PA63 rings. Up to 229 anthrax toxin complexes, equivalent
      to a total of 2400 protein molecules and a mass of about 133 MDa (2.7 times the
      mass of capsid shell), were anchored on a single particle, making it the highest
      density display reported on any virus. The phage T4 capsid lattice provides a
      stable biological platform allowing maximum display of large hetero-oligomeric
      complexes in vitro and offers insights for developing novel vaccines, analysis of
      protein-protein interactions, and structure determination of complexes.

PMID- 16982069
TI  - Emergence of the concept of the basic reproduction number from mathematical
      demography.

PMID- 16982070
TI  - The role of variance in capped-rate stochastic growth models with external
      mortality.
AB  - Techniques from queueing theory can be used to model the growth of individuals in
      a stochastic environment where the growth rate cannot exceed some physiological
      maximum. In the simplifying case where there are no metabolic costs and the
      individual has an unlimited gut size, a general theory for the probability of
      reaching a target weight is presented. The role of environmental variance is
      examined in two different cases; randomly varying prey size and clustering in the
      prey arrival rate. It is argued that when food is scarce environmental
      stochasticity is beneficial to the individual but when food is abundant it can
      lower the chance of survival. The growth and recruitment of larval fish is used
      as an example.

PMID- 16982071
TI  - Diabetes-induced cerebrovascular dysfunction: role of poly(ADP-ribose)
      polymerase.
AB  - Our goal was to identify the role of poly(ADP-ribose) polymerase (PARP) in
      cerebrovascular dysfunction in Type 1 diabetes mellitus (T1D). In a first series
      of studies, rats were assigned to nondiabetic and diabetic (streptozotocin; 50
      mg/kg IP) groups. Two to three months after injection of streptozotocin, we
      examine in vivo responses of pial arterioles to nitric oxide synthase (NOS)
      dependent (adenosine diphosphate (ADP), acetylcholine and histamine) and 
      independent (nitroglycerin) agonists. After the initial examination of reactivity
      to the agonists, we treated pial arterioles acutely with an inhibitor of PARP (PJ
      34; 1 microM), and then we again examined responses to the agonists. In a second
      series of studies, we examine superoxide production (lucigenin chemiluminescence)
      by parietal cortex tissue in nondiabetic and diabetic rats. We found that
      dilation of pial arterioles in response to ADP, acetylcholine and histamine, but
      not to nitroglycerin, was impaired in diabetic compared to nondiabetic rats. In
      addition, although PJ-34 did not alter responses in nondiabetic rats, PJ-34
      alleviated T1D-induced impairment of NOS-dependent vasodilation. We also found
      that basal production of superoxide was increased in diabetic compared to
      nondiabetic rats and that PJ-34 decreased this basal production of superoxide.
      Our findings suggest that T1D impairs NOS-dependent reactivity of cerebral
      arterioles by a mechanism that appears to be related to the formation of
      superoxide via activation of PARP.

PMID- 16982072
TI  - Non-linear chromosomal inversion response in prostate after low dose X-radiation
      exposure.
AB  - Somatic intrachromosomal recombination can result in inversions and deletions in
      DNA, which are important mutations in cancer. The pKZ1 chromosomal inversion
      assay is a sensitive assay for studying the effects of DNA damaging agents using
      chromosomal inversion as a mutation end-point. We have previously demonstrated
      that the chromosomal inversion response in pKZ1 spleen after single low doses of
      X-radiation exposure does not follow the linear no-threshold dose-response model.
      Here, we optimised a chromosomal inversion screening method to study the effect
      of low dose X-radiation exposure in pKZ1 prostatic tissue. In the present study,
      a significant induction in inversions was observed after ultra-low doses of 0.005
      0.01 mGy or after a high dose of 1000 mGy, whereas a reduction in inversions to
      below the sham-treated frequency was observed between 1 and 10 mGy exposure. This
      is the first report of a reduction to below endogenous frequency for any mutation
      end-point in prostate. In addition, the doses of radiation studied were at least
      three orders of magnitude lower than have been reported in other mutation assays
      in prostate in vivo or in vitro. In sham-treated pKZ1 controls and in pKZ1 mice
      treated with low doses of 1-10 mGy the number of inversions/gland cross-section
      rarely exceeded three. Up to 4 and 7 inversions were observed in individual
      prostatic gland cross-sections after doses < or =0.02 mGy and after 1000 mGy,
      respectively. The number of inversions identified in individual cross-sections of
      prostatic glands of untreated mice and all treated mice other than the 1000 mGy
      treatment group followed a Poisson distribution. The dose-response curves and
      fold changes observed after all radiation doses studied were similar in spleen
      and prostate. These results suggest that the pKZ1 assay is measuring a
      fundamental response to DNA damage after low dose X-radiation exposure which is
      independent of tissue type.

PMID- 16982073
TI  - The responses of growing pigs to a chronic-intermittent stress treatment.
AB  - Many of the stressor treatments used in animal models of depression have
      parallels in the normal experiences of domestic pigs. The experiment described
      here aimed to assess whether a chronic-intermittent stress regime caused
      behavioural or physiological changes, indicative of depression, in domestic pigs.
      Ten juvenile male pigs were exposed to a social and environmental stress regime.
      Over the stressor period, weight gain was significantly lower in test pigs than
      in control pigs. Stress treatment had a significant effect on salivary cortisol
      levels, with test pigs having a higher salivary cortisol concentration than
      control pigs after the stress treatment but not before. Test pigs showed less
      ventral lying than control pigs in the post-stress observation. A detrended
      fluctuation analysis (DFA) of postural behavioural organisation showed that test
      pigs had a more structured pattern of activity than controls in the post-stress
      observation and a tendency towards a more structured pattern in the pre-stress
      observation. There were no major behavioural differences between the two groups
      during three repeated open field tests. The results suggest that the stressor
      treatment did create a mild chronic stress, as indicated by the
      hypercortisolaemia and lower weight gain in the test pigs. However, no
      unambiguous behavioural indicators of depression were seen. The behavioural
      analysis did show that fractal techniques, such as DFA, could be applied to pig
      behaviour and that they can reveal extra novel information about the structure of
      an individual's behavioural organisation and how it changes in response to
      complex environmental stressors.

PMID- 16982074
TI  - Food, the law and public health: three models of the relationship.

PMID- 16982075
TI  - Introduction: the importance of law for public health policy and practice.

PMID- 16982076
TI  - Quasispecies and recombination.
AB  - Recombination is introduced into Eigen's theory of quasispecies evolution.
      Comparing numerical simulations of the rate equations in the non-recombining and
      recombining cases show that recombination has a strong effect on the error
      threshold and, for a wide range of mutation rates, gives rise to two stable fixed
      points in the dynamics. This bi-stability results in the existence of two error
      thresholds. However, we prove that, for low mutation rates the bi-stability
      breaks down and the unique equilibrium distribution is concentrated around the
      sequence with highest fitness.

PMID- 16982077
TI  - Protection against the toxicity of microcystin-LR and cylindrospermopsin in
      Artemia salina and Daphnia spp. by pre-treatment with cyanobacterial
      lipopolysaccharide (LPS).
AB  - Purified cyanobacterial lipopolysaccharide (LPS) was not acutely toxic to three
      aquatic invertebrates (Artemia salina, Daphnia magna and Daphnia galeata) in
      immersion trials. However, pre-exposure (24 h) to 2 ngmL(-1) LPS increased the
      LC(50) of microcystin-LR significantly in all 3 species. Similar results were
      observed with A. salina pre-treated with the same concentration of cyanobacterial
      LPS and subsequently exposed to cylindrospermopsin, increasing the LC(50) by 8.
      The findings indicate the need to include exposures to defined combinations of
      cyanotoxins, and in defined sequences, to understand the contributions of
      individual cyanotoxins in accounting for cyanobacterial toxicity to invertebrates
      in natural aquatic environments.

PMID- 16982078
TI  - A new in-vitro agglutination technique for potency estimation of antisnake venom
      serum (ASVS).
AB  - Traditionally the potency of ASVS is assayed quantitatively by in-vivo
      neutralization test for lethality in mice. A sensitive and simple in-vitro
      agglutination assay for the quantitative determination of Antisnake Venom Serum
      (ASVS) potency is reported. The method is rapid, cheap, simple, economical and
      above all does not require the use of experimental animals for potency assay of
      in process, unpurified and purified sera batches. Among in-vitro procedures,
      agglutination assay was favored in comparison to flocculation as the later was
      found to give variable results and also time consuming (high Kf value). Before
      application, the method was standardized and validated for choice and
      concentration of particulate material (latex vs. bentonite), temperature and
      optimum antiserum concentration. It is well known fact that venoms lose toxicity
      on dilution however this study demonstrated that the bentonite adsorbed venoms of
      the entire four snake species viz., Cobra, Krait, Russell's viper and Echis are
      stable even up to 30 days of storage. Among five lots each of unpurified serum,
      unprocessed plasma and purified sera tested, the results were found comparable
      with universally accepted in-vivo biological assay. The coefficient of
      correlation was found to be near 1.0 within 95% fiducial limits of acceptance and
      also significantly less variation was observed in the mean potency values and
      standard deviations. For all results p value was observed to be <0.01. Results
      indicate that in-vitro agglutination assay is suitable and can be used for
      potency estimation of in process as well as unpurified and purified ASVS batches.

PMID- 16982080
TI  - Application of the self-organizing map (SOM) to assess the heavy metal removal
      performance in experimental constructed wetlands.
AB  - The self-organizing map (SOM) model was applied to elucidate heavy metal removal
      mechanisms and to predict heavy metal concentrations in experimental constructed
      wetlands treating urban runoff. A newly developed SOM map showed that nickel in
      constructed wetland filters is likely to leach under high conductivity in
      combination with low pH in winter. In contrast, influent pH and conductivity were
      not shown to have clear relationships with copper (Cu) concentrations in the
      effluent, suggesting that the mobility of Cu was not considerably affected by
      salt increase during winter. The accuracy of prediction with SOM was highly
      satisfactory, suggesting heavy metals can be efficiently estimated by applying
      the SOM model with input variables such as conductivity, pH, temperature and
      redox potential, which can be monitored in real time. Moreover, domain
      understanding was not required to implement the SOM model for prediction of heavy
      metal removal efficiencies.

PMID- 16982079
TI  - Release of cellular proteases into the acidic extracellular milieu exacerbates
      Ebola virus-induced cell damage.
AB  - Ebola virus is highly cytopathic through mechanisms that are largely unknown. We
      present evidence that progressive acidification of the extracellular milieu by
      Ebola virus-infected cells combined with reduced levels of natural cysteine
      protease inhibitor makes the cells vulnerable to uncontrolled proteolysis of
      extracellular matrix components by released active endosomal cathepsins, thereby
      exacerbating Ebola virus-induced cell destruction. The cell surface
      microenvironment was shown to be crucial in aiding this activity. Blocking the
      proteolytic activity with the cathepsin inhibitor E64 resulted in remarkable
      improvements with respect to viral cytopathicity and cell survival despite an
      overwhelmingly high viral load. We propose that the observed enzymatic matrix
      degradation, enhanced by an associated protease/inhibitor imbalance and metabolic
      acidosis, represents an effective viral strategy to boost infection and
      underlies, in part, the remarkable pathogenesis caused by Ebola virus. Further in
      vitro and in vivo research will establish whether a cellular protease with
      hemorrhagic activity is the leading cause of vascular leakage-the hallmark of
      Ebola virus hemorrhagic fever-and help understand the Ebola virus caused cell
      death.

PMID- 16982081
TI  - Trace element level in infant hair and diet, and in the local environment of the
      Moroccan city of Marrakech.
AB  - A sample of 573 infants (aged 0 to 12 months) from the Moroccan city of Marrakech
      was studied in order to determine the level of Pb and Al contaminations. Mean
      values of Pb and Al in children's hair were 6.6 and 9.5 microg/l, respectively.
      Age, gender, and parents' occupation influenced significantly Pb content but not
      Al content. Larger mean values were measured for Al compared with Pb. This
      finding can be explained by a higher level of Al available in both the infant
      diet (complementary feeding) and the local environmental factors (soil and
      drinking water). During weaning, beverages like tea, widely used in Morocco,
      represent an important source of Pb and Al contamination. Al content in drinking
      water is above the international standard.

PMID- 16982082
TI  - Effect of repeated treatment with fluoxetine on tryptophan hydroxylase-2 gene
      expression in the rat brainstem.
AB  - Selective serotonin (5-HT) reuptake inhibitors such as fluoxetine are widely used
      in the treatment of depression and anxiety; however, the mechanisms underlying
      their action and particularly the delay in therapeutic onset remain unclear. It
      is proposed that 5-HT reuptake inhibitors exert their therapeutic activity by
      increasing serotonergic neurotransmission; therefore, the aim of the present
      study was to investigate the effects of repeated treatment with fluoxetine (25
      mg/kg/day p.o., 14 days) on expression of genes coding for proteins that involved
      in the synthesis and reuptake of 5-HT. Exposure of animals to plus-maze
      conditions on the first day of drug administration produced an increase in
      baseline anxiety on subsequent trial 2 weeks later. Fluoxetine strengthened the
      anxiogenic effects of maze experience. Two-week fluoxetine treatment also
      significantly reduced expression of tryptophan hydroxylase-2 (TPH2) and 5-HT
      transporter mRNAs as determined by RT-PCR in the brainstem. These changes were
      consistent with the decreased 5-HT levels and 5-HT turnover in the brain, and
      might contribute to the anxiogenic effects of the drug. The results also suggest
      that recently found association between treatment responses to fluoxetine and
      polymorphic variants of human TPH2 gene [Peters EJ, Slager SL, McGrath PJ,
      Knowles JA, Hamilton SP. Investigation of serotonin-related genes in
      antidepressant response. Mol Psychiatry 2004; 9:879-889] may be related to the
      drug effect on the TPH2 gene expression.

PMID- 16982083
TI  - Influence of induction of parturition on the neonatal acute phase response in
      foals.
AB  - The objectives of the present study were to determine whether induction of
      parturition in mares at term with low doses of oxytocin (2.5 i.u. i.v. every 20
      min) affected the incidence of peri-partum complications or inflammatory
      responses in the neonatal foal. Parturition was induced in 11 of 26 mares and the
      remainder foaled spontaneously. Serum concentrations of amyloid A (AA; an acute
      phase protein) were measured (with a commercial ELISA) from 0 to 72 h postpartum
      in 18 of the neonatal foals. The incidence of dystocia and premature placental
      separation was higher in induced mares (2 of 11 and 1 of 11 versus 0 of 15 and 0
      of 15, respectively), whereas retained fetal membranes were more common in
      spontaneous foalings (2 of 15 versus 0 of 11). When abnormal foals were excluded
      (to decrease the influence of endogenous serum AA elevations), serum
      concentrations of AA increased to the same extent over time in foals with induced
      versus spontaneous parturition; foals with spontaneous parturition had a mean
      serum AA concentration of 7.8 microg/mL at birth that increased to a maximum of
      58.9 microg/mL at 36 h; foals with induced parturition had a mean serum AA
      concentration of 5.4 microg/mL at birth that increased to a maximum of 41.4
      microg/mL at 48 h. Baseline serum AA concentrations were lower in induced foals.
      We concluded that inducing parturition with low doses of oxytocin in mares at
      term did not affect (relative to spontaneous parturition) the temporal dynamics
      of serum AA concentrations in the normal foal in the first 72 h of life. However,
      the induction procedure may lead to complications during parturition that, if not
      detected early, could result in the development of an inflammatory response in
      the neonate.

PMID- 16982084
TI  - Pharmacotherapy of aphasia: myth or reality?
AB  - Pharmacotherapy of aphasia had been discussed for the last twenty years with
      first bromocriptine and amphetamine and then serotoninergic, GABAergic and
      cholinergic agents. Here, we reviewed the MEDLINE available reports of drug
      therapy for aphasia. So far, proofs of efficiency were found indubitable for none
      of the studied molecules. However, some of them showed limited efficiency
      (piracetam and amphetamine). Moreover, drug therapies for aphasia were less
      efficient alone than when they were associated with speech therapy.

PMID- 16982085
TI  - Phoneme monitoring in silent naming and perception in adults who stutter.
AB  - The present study investigated phonological encoding skills in persons who
      stutter (PWS). Participants were 10 PWS (M=31.8 years, S.D.=5.9) matched for age,
      gender, and handedness with 12 persons who do not stutter (PNS) (M=24.3 years,
      S.D.=4.3). The groups were compared in a phoneme monitoring task performed during
      silent picture naming. The phonological complexity of the target items in the
      task was varied such that participants monitored either compound words or noun
      phrases. Performance in this task was compared to phoneme monitoring performed on
      aurally presented target words to investigate whether any differences observed in
      silent naming were also evident in perception. Analysis of the response time
      data, in milliseconds, indicated that PWS were significantly slower as compared
      to PNS in phoneme monitoring during silent naming; group differences were not
      obtained in the perception task. The groups were also comparable in the response
      time to phoneme monitoring within compound words and noun phrases in both silent
      naming and perception. The findings suggested that PWS were slower in the
      encoding of segmental, phonological units during silent naming. Furthermore,
      absence of such differences in perception ruled out a general monitoring deficit
      in PWS. Findings are interpreted within the context of the psycholinguistic
      theories of stuttering that postulate phonological encoding and/or monitoring as
      a causal variable in stuttering. EDUCATIONAL OBJECTIVES: As a result of this
      activity, the participant should: (1) describe relevant literature on
      phonological encoding skills in children and adults who stutter, (2) identify
      paradigms that can be used to investigate phonological processing in PWS, and (3)
      discuss the role of phonological encoding in speech production.

PMID- 16982086
TI  - Comparing judgments of stuttering made by students, clinicians, and highly
      experienced judges.
AB  - PURPOSE: The purpose of this study was to compare judgments of stuttering made by
      students and clinicians with previously available judgments made by highly
      experienced judges in stuttering. METHOD: On two occasions, 41 university
      students and 31 speech-language pathologists judged the presence or absence of
      stuttering in each of 216 audiovisually recorded 5-s intervals of the speech of
      adults who stutter. Intrajudge and interjudge agreement were calculated, and
      comparisons were made to judgments previously made about the same recordings by
      10 highly experienced judges of stuttering. RESULTS: Students and clinicians
      showed similar and relatively high levels of intrajudge and interjudge agreement,
      but both students and clinicians identified less than half as much stuttering as
      the highly experienced judges had identified. CONCLUSIONS: These results
      replicate previous findings of high agreement coexisting with low accuracy in
      students' judgments of stuttering, extending those findings to show that similar
      problems are evident in judgments made by practicing clinicians. Implications
      include the need for explicit stuttering judgment training programs for both
      students and practicing clinicians. EDUCATIONAL OBJECTIVES: After reading this
      article, the reader will be able to: (1) describe different methods for
      identifying stuttering and possible problems associated with each method; (2)
      describe two different methods for reporting interjudge reliability; (3) describe
      how the identification of stuttering differs for student, clinician, and highly
      experienced judges.

PMID- 16982087
TI  - Fracture toughness comparison of three test methods with four dental porcelains.
AB  - OBJECTIVE: The aim of this study was to compare three fracture toughness test
      methods, using four commercial dental porcelains. MATERIALS AND METHODS: The
      fracture toughness test techniques involved were: the single-edge-notched beam
      (SENB), the indentation strength method (IS), and a rather convenient ASTM
      standard for advanced ceramics, which is still rarely used in dental ceramic
      research, the Chevron-notched beam method (CN). Duceram, Duceram LFC, Sintagon Zx
      and Carrara Vincent were chosen for study. Data was analyzed by two-way and
      paired ANOVA. RESULT: No statistical difference was found between the CN and SENB
      methods with four dental porcelains, but IS was not always in statistical
      agreement with SENB or CN. Statistical agreement among all three methods occurred
      only with Duceram LFC. CONCLUSION: The different test methods did not always lead
      to the same ranking or values of fracture toughness. Yet the toughness results of
      the SENB method were comparable to those of the CN method for all the four dental
      porcelains tested in this study.

PMID- 16982088
TI  - Patterns of variation among distinct alleles of the Flag silk gene from Nephila
      clavipes.
AB  - Spider silk proteins and their genes are very attractive to researchers in a wide
      range of disciplines because they permit linking many levels of organization.
      However, hypotheses of silk gene evolution have been built primarily upon single
      sequences of each gene each species, and little is known about allelic variation
      within a species. Silk genes are known for their repeat structure with high
      levels of homogenization of nucleotide and amino acid sequence among repeated
      units. One common explanation for this homogeneity is gene convergence. To test
      this model, we sequenced multiple alleles of one intron-exon segment from the
      Flag gene from four populations of the spider Nephila clavipes and compared the
      new sequences to a published sequence. Our analysis revealed very high levels of
      heterozygosity in this gene, with no pattern of population differentiation. There
      was no evidence of gene convergence within any of these alleles, with high levels
      of nucleotide and amino acid substitution among the repeating motifs. Our data
      suggest that minimally, there is relaxed selection on mutations in this gene and
      that there may actually be positive selection for heterozygosity.

PMID- 16982089
TI  - The potential role of fucosylated cationic liposome/NFkappaB decoy complexes in
      the treatment of cytokine-related liver disease.
AB  - Cytokine production by Kupffer cells, which is regulated by NFkappaB, causes
      severe liver injury in endotoxin syndrome. NFkappaB decoy has been reported to
      inhibit NFkappaB-mediated transcription. The purpose of this study is to inhibit
      LPS-induced cytokine production by Kupffer cell-targeted delivery of NFkappaB
      decoy using fucosylated cationic liposomes (Fuc-liposomes). Cholesten-5-yloxy-N
      {4-[(1-imino-2-L-thiofucosyl-ethyl)-amino] butyl-}formamide (Fuc-C4-Chol) was
      synthesized to prepare Fuc-liposomes. Tissue accumulation, intrahepatic
      distribution and serum cytokine concentrations were investigated after
      intravenous injection of Fuc-liposomes/NFkappaB decoy complexes. Intravenously
      injected Fuc-liposome complexes rapidly and highly accumulated in the liver while
      little naked NFkappaB decoy accumulated in the liver. An intrahepatic
      distribution study showed that Fuc-liposome complexes are mainly taken up by non
      parenchymal cells. The liver accumulation of Fuc-liposome complexes was inhibited
      by GdCl(3) pretreatment, which selectively inhibited Kupffer cell uptake. This
      result suggested that Kupffer cells contribute to liver accumulation. TNFalpha,
      IFNgamma, ALT and AST serum levels in LPS-infected mice were significantly
      attenuated by treatment with Fuc-liposome complexes compared with naked NFkappaB
      decoy. Fuc-liposome complexes also reduced the amount of activated NFkappaB in
      the liver nuclei. Fuc-liposomes would be a useful carrier for Kupffer cell
      selective delivery of NFkappaB decoy by intravenous injection.

PMID- 16982090
TI  - Effect of construct properties on encapsulated chondrocyte expression of insulin
      like growth factor-1.
AB  - Hydrogels are a promising type of biomaterial for articular cartilage constructs
      since they have been shown to enable encapsulated chondrocytes to express their
      predominant phenotypic marker, type II collagen. Endogenously expressed signaling
      molecules, such as insulin-like growth factor-1 (IGF-1), are also known to
      facilitate the retention of this chondrocytic phenotype. Recent investigations
      have attempted to enhance the ability of encapsulated chondrocytes to regenerate
      cartilage through delivery of exogenous signaling molecules. However, we
      hypothesize that by altering construct properties, such as cell density and
      polymer concentration, we can augment the expression of endogenous IGF-1 in
      chondrocytes. To this end, bovine articular chondrocytes were encapsulated within
      alginate hydrogels at two different cell densities (25,000 and 100,000
      cells/bead) and various alginate concentrations (0.8%, 1.2%, and 2.0% w/v). These
      parameters were chosen to simultaneously investigate cell-to-cell distance on
      paracrine signaling and water content on IGF-1 diffusion by chondrocytes. At 1,
      4, and 8d, chondrocytes were analyzed for protein and mRNA expression of IGF-1 as
      well as type II collagen. Results suggest that cell density and alginate
      concentration at high cell density can significantly affect the endogenous IGF-1
      expression by chondrocytes. Therefore, these results indicate that construct
      properties can impact chondrocyte gene expression and should be considered in
      order to create a proper engineered articular cartilage construct.

PMID- 16982091
TI  - Techniques for biological characterization of tissue-engineered tendon and
      ligament.
AB  - Injuries to tendons and ligaments are prevalent and result in a significant
      decrease in quality of patient life. Tissue-engineering strategies hold promise
      as alternatives to current treatments for these injuries, which often fail to
      fully restore proper joint biomechanics and produce significant donor site
      morbidity. Commonly, tissue engineering involves the use of a three-dimensional
      scaffold seeded with cells that can be directed to form tendon/ligament tissue.
      When determining the success of such approaches, the viability and proliferation
      of the cells in the construct, as well as extracellular matrix production and
      structure should be taken into account. Histology and histochemistry, microscopy,
      colorimetric assays, and real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) are techniques that are employed to assess these biological
      characteristics. This review provides an overview of each of these methods,
      including specific examples of how they have been used in evaluation of tissue
      engineered tendon and ligament tissue. Basic physical principles underlying each
      method and advantages and disadvantages of the various techniques are summarized.

PMID- 16982092
TI  - T-cell type lymphoproliferative disease of granular lymphocytes (LDGL) is
      equipped with a phenotypic pattern typical of effector cytotoxic cells.
AB  - By analyzing the expression of several cytotoxic markers, killer-immunoglobulin
      like receptors (KIRs), CD94/CD159, CD314 and natural cytotoxicity receptors
      (NCRs), in 22 CD3+ lymphoproliferative disease of granular lymphocyte (LDGL)
      patients we investigated whether granular lymphocytes (GLs) displayed the
      phenotype of fully differentiated cytotoxic cells. Our results demonstrate that
      GLs express a pattern consistent with fully differentiated CTLs. KIRs are
      expressed only in a fraction of patients (7/22), as is CD94/CD159 (5/22). In
      conclusion, GLs in CD3+ LDGL patients typically show the phenotype of fully
      differentiated CTL, whereas the expression of NK receptors does not represent a
      common feature of the proliferating clone.

PMID- 16982093
TI  - Childhood adversity, poly-substance use, and disordered eating in adolescent
      Latinas: mediated and indirect paths in a community sample.
AB  - OBJECTIVE: Although many studies have identified associations between childhood
      maltreatment and later substance use and disordered eating, few have examined
      causal or explanatory pathways, and whether victim characteristics predict the
      development of one versus the other of these outcomes remains uninvestigated.
      Furthermore, relatively little childhood maltreatment research has examined
      Latino samples. To address these gaps, this study examined among Latina
      adolescents the effects of sexual abuse, physical/emotional abuse, neglect,
      disconnection from family, and parental alcohol problems on poly-substance use
      and disordered eating, and whether five individual characteristics explain or
      differentiate these outcomes. METHOD: Data from a community sample of 361 Latina
      adolescents were analyzed using structural equation modeling. RESULTS:
      Physical/emotional abuse predicted poly-substance use and weight concerns, and
      these associations were mediated by impaired current attachment. Disconnection
      from family predicted bulimic behaviors, and this association was mediated by
      dysphoria. One indirect path also emerged: Disconnection from family predicted
      low social conformity, and low social conformity predicted poly-substance use.
      Childhood sexual abuse did not uniquely predict any adverse outcome or individual
      characteristic examined. CONCLUSIONS: Dysphoria and impaired current attachment
      appear to play important roles in the development of substance use and disordered
      eating in Latina adolescents when physical/emotional abuse or disconnection from
      family predicts these outcomes. Dysphoria and low social conformity may
      differentiate the development of bulimic behaviors and poly-substance use,
      respectively, when family disconnection predicts these outcomes.

PMID- 16982095
TI  - Building beauty: physiognomy on the gas-lit stage.
AB  - From 1816 onwards, London theatres began to install gas-lighting systems to
      replace candles. In addition to allowing theatre managers to adjust the level of
      illumination, gas lights offered greater brightness and visibility for the
      audience. Actors had to adjust to this new level of exposure that threatened
      their ability to "look the part." Until this illuminating moment, there had been
      little need for makeup and actors to adhere to the principles of physiognomy--a
      system that correlated character traits to facial features. Under the new harsh
      glare of the gas lights, both the faces of the actors and the theatres themselves
      were found wanting.

PMID- 16982094
TI  - Depressive-like behavior and high alcohol drinking co-occur in the FH/WJD rat but
      appear to be under independent genetic control.
AB  - This review will consider the evidence supporting the view that a specific
      substrain of Fawn-Hooded rat (FH/Wjd) exhibits co-occurring depressive-like
      behavior and high alcohol intake independently. First, the FH/Wjd rat is compared
      with other Fawn-Hooded substrains (FH/Har, FHH/Eur, FHL/Eur) and it is concluded
      that only the FH/Wjd rat is both highly immobile in the forced swim test and
      drinks substantial amounts of 5-10% alcohol voluntarily. Next it is demonstrated
      that the FH/Wjd rat fulfils many of the criteria proposed for an animal model of
      alcoholism (becomes tolerant, becomes dependent and expresses withdrawal
      symptoms, bar-presses for alcohol). Other literature in addition to the high swim
      test immobility suggests that the FH/Wjd rat may also be an animal model of
      depression (high basal corticosterone levels, blunted hormonal responses to
      serotonergic agonists). To study the phenotypes more closely an inbred strain
      (ACI/N) of rat that drank little alcohol voluntarily and exhibited considerable
      swimming in the forced swim test (i.e., low immobility) was obtained. A
      systematic intercrossing of the parental strains and the resulting F1 progeny was
      carried out to generate more than 800 F2s. Swim test immobility, alcohol intake
      and preference and saccharin intake are four of the 7 variables assessed in each
      of these rats. Using classical quantitative genetics methods, it was determined
      that these four phenotypes exhibited modest heritability and were influenced by
      multiple genes. Correlation coefficients between immobility and the other
      measures were near zero, whereas alcohol intake and preference were highly
      correlated (r=0.9) and alcohol and saccharin intakes were modestly correlated
      (r=0.3). A final study showed that chronic fluoxetine treatment counteracted the
      high immobility but did not affect alcohol intake, similar to human studies.
      These findings suggest that although depressive-like behavior and high alcohol
      intake co-occur in the FH/Wjd rat, they are independently regulated.

PMID- 16982096
TI  - Molecular cloning and characterisation of a proteinase inhibitor, alpha 2
      macroglobulin (alpha2-M) from the haemocytes of tiger shrimp Penaeus monodon.
AB  - An alpha 2-macroglobulin (alpha2-M) gene was cloned from the haemocytes of tiger
      shrimp Penaeus monodon by RT-PCR, cloning and sequencing of overlapping PCR and
      rapid amplification of cDNA ends (RACE) method. Analysis of the nucleotide
      sequence revealed that the alpha2-M cDNA consists of 4876 bp with an open reading
      frame (ORF) of 4494 bp, a 52 bp 5'-untranslated region, and a 327 bp 3'
      untranslated region containing a poly A signal. The open reading frame encodes a
      protein of 1498 amino acids with 18 residues signal sequence. The predicted
      molecular mass of the mature protein (1480 amino acids) is 167.7 kDa with an
      estimated pI of 5.30. The P. monodon alpha2-M sequence contains putative
      functional domains including a GCGEQNM thioester region, a bait region, and a
      receptor-binding domain which are present in other invertebrate and vertebrate
      alpha2-Ms. Sequence comparison showed that alpha2-M deduced amino acid sequence
      of P. monodon has an overall similarity of 85, 52 and 49% to that of kuruma
      shrimp Marsupenaeus japonicus, American horseshoe crab Limulus polyphemus and mud
      crab Scylla serrata, respectively. Alignment of the deduced amino acid sequence
      to other species alpha2-M showed that the overall structure is evolutionarily
      conserved and phylogenetic analysis revealed that P. monodon alpha2-M is closely
      related to other arthropod alpha2-M, and displays the highest similarity to M.
      japonicus alpha2-M. The alpha2-M was mainly expressed in haemocytes, but not in
      eyestalk, gill, muscle, hepatopancreas, and intestine. Quantitative real-time RT
      PCR analysis showed that alpha2-M mRNA transcript in haemocytes of P. monodon
      increased significantly in 12, 24 and 48 h post-peptidoglycan (PG) injection, but
      returned to the original values in 72 h post-PG injection.

PMID- 16982097
TI  - Collagen and major histocompatibility class II expression in mesenchymal cells
      from CIITA hypomorphic mice.
AB  - Major histocompatibility class II (MHC II) transactivator (CIITA) is critical for
      interferon-gamma (IFN-gamma)-induced repression of collagen [Xu, Y., Wang, L.,
      Buttice, G., Sengupta, P.K., Smith, B.D., 2004. Major histocompatibility class II
      transactivator (CIITA) mediates repression of collagen (COL1A2) transcription by
      interferon gamma (IFN-gamma). J. Biol. Chem. 279, 41319-41332] and activation of
      MHC II transcription. To better understand the role of CIITA and IFN-gamma
      induced repression of collagen, mesenchymal cells (lung fibroblasts, adventitial
      fibroblasts, and smooth muscle cells) were isolated from a CIITA deficient mouse
      (C2ta(tm1Ccum)). IFN-gamma induced MHC II expression and repressed collagen type
      I expression in all three cell types isolated from the wild type background. As
      expected, IFN-gamma treatment of cells isolated from CIITA deficient mice did not
      induce MHC II production or activate the MHC II promoter. Interestingly, collagen
      gene expression and promoter activity was similar to that of wild type. Moreover,
      IFN-gamma induced CIITA mRNA and a truncated form of CIITA protein in all cells
      isolated from CIITA deficient mice. Most importantly, truncated CIITA occupied
      the collagen alpha 2(I) gene (col1a2) transcription start site during IFN-gamma
      treatment, but it did not occupy the MHC II promoter as judged by chromatin
      immunoprecipitation assays. Exogenous expression of a similar truncated form of
      CIITA maintained its ability to repress col1a2 transcription, but lost its
      ability to activate MHC II gene transcription suggesting a role for the CIITA C
      terminal domain in activation, but not repression. IFN-gamma induced primarily
      types I and IV CIITA isoforms in the mouse cells. All three isoforms of CIITA
      were capable of repressing col1a2 and activating MHC II gene transcription. These
      data suggest that the previously described CIITA knockout mouse carries a
      hypomorphic mutation, rather than a null mutation. The removal of the leucine
      rich region in CIITA blocks activation of MHC II without altering repression of
      collagen transcription.

PMID- 16982098
TI  - Activating transcription factor 3 (ATF3) represses the expression of CCL4 in
      murine macrophages.
AB  - Acute expression of macrophage inflammatory protein-1 beta (also known as CCL4)
      promotes beneficial leukocyte recruitment to infected tissues, but chronic
      expression of this chemokine contributes to inflammatory disease. CCL4 expression
      is controlled largely at the transcriptional level and an ATF/CRE sequence
      located in the promoter (-104 to -97bp, relative to the transcriptional start
      site) has been identified as a critical cis-acting element. The trans-acting
      binding proteins that influence CCL4 transcription via this site are largely
      unknown. We investigated whether activating transcription factor 3 (ATF3), a
      member of the ATF/CREB family of transcription factors, binds to the CCL4 ATF/CRE
      site in macrophages. Using the electrophoretic mobility shift assay and the
      chromatin immunoprecipitation assay, we found that ATF3 binds to the ATF/CRE site
      within the CCL4 promoter in untreated and lipopolysaccharide (LPS)-stimulated
      macrophages. Quantitative RT-PCR analysis showed that CCL4 mRNA levels in
      elicited peritoneal macrophages from ATF3(-/-) mice are significantly higher than
      in congenic ATF3(+/+) macrophages under both unstimulated and LPS-stimulated
      conditions, suggesting that ATF3 represses transcription of the CCL4 gene.
      Consistent with the higher gene expression, ATF3-deficient macrophages secreted
      more CCL4 protein than ATF3(+/+) macrophages. Similar results were obtained in
      bone-marrow-derived macrophages treated with Toll-like receptor 2, 3, 4 and 5
      agonists. Thus, we conclude that ATF3 constitutively binds to the ATF/CRE site in
      the CCL4 promoter where it represses basal and pathogen-associated molecular
      pattern (PAMP)-stimulated transcription. Consequently, ATF3 appears to be part of
      a control mechanism that limits the amount of CCL4 released by macrophages,
      preventing excessive inflammation.

PMID- 16982099
TI  - Effects of sarin and cyclosarin exposure during the 1991 Gulf War on
      neurobehavioral functioning in US army veterans.
AB  - BACKGROUND: During the Gulf War (GW), in early March 1991, a munitions dump at
      Khamisiyah, Iraq, was destroyed. Later, in 1996, the dump was found to have
      contained the organophosphate chemical warfare agents, sarin and cyclosarin.
      METHODS: Data collected in a study conducted between 1994 and 1996, before the
      Khamisiyah incident was publicly disclosed, were used to examine neurobehavioral
      task performances of GW veterans (n=140) categorized as having received high,
      moderate, or low-to-no exposure dose levels to sarin and cyclosarin at
      Khamisiyah, Iraq. Exposure levels were based on modeled estimates of the exposure
      plume and on troop location information at the time of the Khamisiyah event.
      Based on recent findings observed in follow-up studies of persons exposed to
      sarin during the 1995 terrorist attacks in Japan, we hypothesized that exposure
      to sarin and cyclosarin would be associated with poorer performances on objective
      neurobehavioral tasks in specific functional domains (particularly in
      visuospatial abilities and psychomotor functioning) in a dose-dependent manner.
      RESULTS: Sarin and cyclosarin exposure was significantly associated with less
      proficient neurobehavioral functioning on tasks involving fine psychomotor
      dexterity and visuospatial abilities 4-5 years after exposure. CONCLUSIONS:
      Findings suggest a dose-response association between low-level exposure to sarin
      and cyclosarin and specific functional central nervous system effects 4-5 years
      after exposure.

PMID- 16982100
TI  - Optimal HP configurations of proteins by combining local search with elastic net
      algorithm.
AB  - The prediction of protein conformation from its amino-acid sequence is one of the
      most prominent problems in computational biology. But it is NP-hard. Here, we
      focus on an abstraction widely studied of this problem, the two-dimensional
      hydrophobic-polar protein folding problem (2D HP PFP). Mathematical optimal model
      of free energy of protein is established. Native conformations are often sought
      using stochastic sampling methods, but which are slow. The elastic net (EN)
      algorithm is one of fast deterministic methods as travelling salesman problem
      (TSP) strategies. However, it cannot be applied directly to protein folding
      problem, because of fundamental differences in the two types of problems. In this
      paper, how the 2D HP protein folding problem can be framed in terms of TSP is
      shown. Combination of the modified elastic net algorithm and novel local search
      method is adopted to solve this problem. To our knowledge, this is the first
      application of EN algorithm to 2D HP model. The results indicate that our
      approach can find more optimal conformations and is simple to implement,
      computationally efficient and fast.

PMID- 16982101
TI  - Genome conservation between the bovine and human interleukin-8 receptor complex:
      improper annotation of bovine interleukin-8 receptor b identified.
AB  - Interleukin (IL)-8 and its receptors, CXCR1 and CXCR2, are key regulators of
      inflammation. However, knowledge of these receptors at the genomic level is
      limiting or absent in cattle. Therefore, our objective was to identify bovine
      orthologs of human CXCR1 and CXCR2. Alignment of bovine CXCR2 reference mRNA to
      the bovine genome revealed two regions of similarity on BTA2 approximately 20 kb
      apart and on opposite strands. Comparison with the human genome suggested the
      more centromeric region to be CXCR2 and the more telomeric region to be CXCR1
      which contradicts the current annotation of the bovine CXCR2 reference mRNA. This
      observation was verified by sequencing RT-PCR products of specific regions within
      each predicted IL-8 receptor and comparing with human sequences using ClustalW.
      Further examination of coding and non-coding regions within the IL-8 receptor
      genome complex revealed that both bovine and canine CXCR1 and CXCR2 genes had
      more conserved sequences in common with the human genes than either mouse or rat,
      and may offer more suitable animal models for certain applications. This
      molecular information provides a stepping stone for greater understanding of the
      role each IL-8 receptor plays in inflammation and will enhance our ability to
      develop strategies against inflammatory based diseases.

PMID- 16982102
TI  - Targeted disruption of the genes, mlcR and ariB, which encode GAL4-type proteins
      in Penicillium citrinum.
AB  - The role of two genes, mlcR and ariB, was investigated by gene disruption
      experiments. The mlcR gene in the ML-236B biosynthetic gene cluster of
      Penicillium citrinum encodes a putative 50.2-kDa protein with a Zn (II) 2Cys6 DNA
      binding domain, and has similarity to most of the GAL4-type regulatory proteins.
      The mlcR disruptant did not produce ML-236B or its intermediates, suggesting that
      mlcR is involved in ML-236B biosynthesis. Transcriptional analysis of the mlcR
      disruptant by Northern hybridization and RT-PCR indicated that MlcR activates the
      transcription of mlcA, B, C,D, F, G and H in a pathway-specific manner. On the
      other hand, MlcR did not affect the transcription of mlcE and the genes outside
      the ML-236B cluster. The ariB gene, next to mlcR, encodes another GAL4-type
      protein. Transcriptional analysis of the ariB disruptant indicated that it is a
      transcriptional activator of the genes outside the ML-236B cluster, and is not
      related to ML-236B biosynthesis.

PMID- 16982103
TI  - Caregiving in the Philippines: a quantitative survey on adult-child caregivers'
      perceptions of burden, stressors, and social support.
AB  - This study aims to describe the present caregiving situation of Filipino adult
      child caregivers (CGs) particularly aiming to identify the predictors of CG
      burden and to assess the effect of social support on stressors and perception of
      burden. A cross-sectional survey employing face-to-face interviews with 193 adult
      child CGs in Davao City, Philippines, measured the perception of burden using the
      Cost of Care Index (CCI) by Kosberg and Cairl. Results indicated the majority
      were daughter CGs living with their elderly parents, who were receiving high
      levels of informal social support. A moderate to high level of burden perception
      (mean+/-S.D. score of 47.0+/-9.1) was found among respondents. CGs with higher
      educational attainment showed low burden perception. However, higher family
      income and higher State-Trait Anxiety Inventory (STAI) anxiety scores were
      associated with higher burden perception. Also, longer caregiving hours, a male
      care recipient (CR), and the presence of CR's memory and behavior problems
      predicted higher CG burden. The interaction between stressors and perceived
      burden showed that social support provided a buffering effect for CGs
      experiencing higher burden perception. This suggests that respite and support
      resources including community-based counseling and education programs to assist
      CGs in dealing with stress may positively contribute to reduce burden.

PMID- 16982104
TI  - Financial analysis of various strategies for the control of Neospora caninum in
      dairy cattle in Switzerland.
AB  - The present study was conducted to estimate the direct losses due to Neospora
      caninum in Swiss dairy cattle and to assess the costs and benefits of different
      potential control strategies. A Monte Carlo simulation spreadsheet module was
      developed to estimate the direct costs caused by N. caninum, with and without
      control strategies, and to estimate the costs of these control strategies in a
      financial analysis. The control strategies considered were "testing and culling
      of seropositive female cattle", "discontinued breeding with offspring from
      seropositive cows", "chemotherapeutical treatment of female offspring" and
      "vaccination of all female cattle". Each parameter in the module that was
      considered to be uncertain, was described using probability distributions. The
      simulations were run with 20,000 iterations over a time period of 25 years. The
      median annual losses due to N. caninum in the Swiss dairy cow population were
      estimated to be euro 9.7 million euros. All control strategies that required
      yearly serological testing of all cattle in the population produced high costs
      and thus were not financially profitable. Among the other control strategies, two
      showed benefit-cost ratios (BCR) >1 and positive net present values (NPV):
      "Discontinued breeding with offspring from seropositive cows" (BCR=1.29, NPV=25
      million euros ) and "chemotherapeutical treatment of all female offspring"
      (BCR=2.95, NPV=59 million euros). In economic terms, the best control strategy
      currently available would therefore be "discontinued breeding with offspring from
      seropositive cows".

PMID- 16982105
TI  - Cavum septi pellucidi and intrusive recollections in cancer survivors.
AB  - A previous study reported abnormally large cavum septi pellucidi (CSP) in
      posttraumatic stress disorder (PTSD). We utilized magnetic resonance imaging to
      examine the frequency of large CSP, as defined by Nopoulos et al. (1997), in
      cancer survivors with and without intrusive recollections in a sample identical
      to that of our previous study. The frequency of large CSP did not differ between
      the two groups. The results suggest that alteration in midline structures during
      the course of neurodevelopment may lead to severe PTSD, while subthreshold PTSD,
      such as intrusive recollections, appear not to be associated with such
      alterations.

PMID- 16982106
TI  - Sequential gene integration for the engineering of Kluyveromyces marxianus.
AB  - The attributes of the yeast Kluyveromyces marxianus (rapid growth rate at high
      temperature, utilization of a wide range of inexpensive carbon sources) make it a
      promising industrial host for the synthesis of protein and non-protein products.
      However, no stable multicopy plasmids are currently available for long-term
      culture of K. marxianus. To allow the stable genetic/metabolic engineering of K.
      marxianus, a method for integrating precise numbers of the same or different
      genes was developed for this yeast. A K. marxianus URA3 deletion mutant was
      constructed and the URA3 blaster (UB) reusable selection cassette from
      Saccharomyces cerevisiae was used to select sequential, untargeted chromosomal
      insertions of the Bacillus megaterium lactate dehydrogenase (LDH) gene. Following
      excision of the UB cassette from the chromosomes, the integrating vector was
      retransformed into the strain and a second copy of LDH was inserted,
      demonstrating the success of this method for sequential gene integrations in K.
      marxianus. LDH activity and lactic acid concentration increased with each gene
      insertion, further illustrating the success of this method.

PMID- 16982107
TI  - Metabolic syndrome does not increase the risk of conversion of impaired glucose
      tolerance to diabetes in Asian Indians--Result of Indian diabetes prevention
      programme.
AB  - AIMS: In this study, we assessed for the prevalence of metabolic syndrome (MetS)
      in the cohort of subjects with impaired glucose tolerance (IGT) in the Indian
      Diabetes Prevention Programme and studied whether the syndrome enhanced the
      conversion to diabetes. METHODS: Effectiveness of lifestyle modification (LSM),
      metformin (Met) and LSM plus Met was tested in a randomised, controlled primary
      prevention study in subjects with IGT n=502 (M:W 397:105) at a median follow up
      of 30 months. Baseline prevalence of MetS was calculated using the WHO criteria.
      Insulin resistance (IR) was calculated using homeostasis model assessment (HOMA)
      method. RESULTS: MetS was present in 233 subjects (46.4%; 95% CI 41.9-50.9) in
      the total group, in men (n=168; 42.3%; 95% CI 37.4-47.3) and in women (n=65;
      61.9%; 95% CI 51.9-71.2) (men versus women chi(2)=12.8, p=0.0005). Insulin
      resistance (HOMA-IR>or=4.1) was present in 69.1% with no gender difference. IR
      increased proportionately with increasing number of abnormalities, in IGT
      (39.8%), IGT plus one abnormality (56.5%) and IGT plus any two or more
      abnormalities (69.1%) (Mantel Haenszel chi(2)=22.8, p<0.0001). Incidence of
      diabetes was similar in subjects with (40.3%) (n=94/233) or without (40.1%)
      (n=108/269) MetS (p=0.97). Cox's regression analysis confirmed that MetS did not
      enhance the conversion rate of IGT to diabetes both in the control (HR=0.88, 95%
      CI 0.53-1.47, p=0.63) and in the total group (HR=1.02, 95% CI 0.78-1.35, p=0.88),
      after correcting for effects of intervention. CONCLUSION: Prevalence of MetS is
      high in Asian Indian IGT subjects, especially in women. However, it did not
      influence the rate of conversion of IGT to diabetes.

PMID- 16982108
TI  - "Return to sender, address unknown...." Are variant addressins involved in PSC?

PMID- 16982109
TI  - Large liver cell dysplasia: a controversial entity.
AB  - Large cell change (LCC) is a noncommittal term used today to indicate liver cell
      dysplasia of the large cell type. Dysplasia was deleted from the original
      definition because not enough evidence has been collected over time to support
      premalignancy. LCC is a microscopically well-defined lesion, usually found in
      cirrhosis, whose origin, natural history, and fate are still debated. Different
      morphologic, phenotypic, molecular and clinical studies have been performed to
      address the issue of the dysplastic versus reactive nature of this lesion. The
      aim of this review is to critically evaluate the contributions to the topic and
      to underline that the heterogeneity of the lesion is an important issue to be
      taken into account for our biological understanding of it. While LCC has
      important morphologic analogies in experimental liver carcinogenesis, no
      comparable lesions are known in solid non-liver parenchymal human tissues that
      morphologically feature dysplasia, but in which it is uncertain whether the
      lesions are reactive or preneoplastic. The debate over the lesion may be useful
      in learning the actual limits of morphology and how additional information can be
      gained by looking inside the cells.

PMID- 16982110
TI  - Hypolocomotion in rats with chronic liver failure is due to increased glutamate
      and activation of metabotropic glutamate receptors in substantia nigra.
AB  - BACKGROUND/AIMS: Patients with hepatic encephalopathy show altered motor
      function, psychomotor slowing and hypokinesia. The underlying mechanisms remain
      unclear. This work's aims were: (1) to analyse in rats with chronic liver failure
      due to portacaval shunt (PCS) the neurochemical alterations in the basal ganglia
      thalamus-cortex circuits; (2) to correlate these alterations with those in motor
      function and (3) to normalize motor activity of PCS rats by pharmacological
      means. METHODS: Extracellular neurotransmitters levels were analysed by in vivo
      brain microdialysis. Motor activity was determined by counting crossings in open
      field. RESULTS: Extracellular glutamate is increased in substantia nigra pars
      reticulata (SNr) of PCS rats. Blocking metabotropic receptor 1 (mGluR1) in SNr
      normalizes motor activity in PCS rats. In ventro-medial thalamus of PCS rats GABA
      is increased and it is normalized by blocking mGluR1 in SNr. Blocking mGluR1 in
      SNr increases and mGluR1 activation reduces glutamate in motor cortex and motor
      activity. CONCLUSIONS: Increased extracellular glutamate and activation of mGluR1
      in SNr are responsible for reduced motor activity in rats with chronic liver
      failure. Blocking mGluR1 in SNr normalizes motor activity in PCS rats, suggesting
      that, under appropriate conditions, similar treatments could be useful to treat
      the psychomotor slowing and hypokinesia in patients with hepatic encephalopathy.

PMID- 16982112
TI  - Power calculations for generalized linear models in observational longitudinal
      studies: a simulation approach in SAS.
AB  - Repeated measurements arising from longitudinal studies occur frequently in
      applied research. Methods to calculate power in the context of repeated measures
      are available for experimental settings where the covariate of interest is a
      discrete treatment indicator. However, no closed form expression exists to
      calculate power for generalized linear models with non-zero within-cluster
      correlation that are common in epidemiological and observational studies in which
      the covariate of interest varies over time and is often measured on a continuous
      scale, and where the researchers control for several potential confounders. We
      describe a Monte Carlo simulation approach conducted to calculate power, and
      illustrate its application in two models frequently encountered in practice, the
      normal linear mixed model, and the logistic regression model, both with repeated
      measurements and non-zero within-cluster correlation. This approach can be used
      to calculate the effect on power of changing various simulation conditions
      controlled by the researcher, such as sample size, within-cluster correlation
      structure, smallest meaningful difference to detect, and distributional
      assumptions.

PMID- 16982113
TI  - Association of genetic polymorphisms in the base excision repair pathway with
      lung cancer risk: a meta-analysis.
AB  - Lung cancer is a major cause of cancer-related death in the developed countries
      and the overall survival rate has still an extremely poor. Although cigarette
      smoking is the main cause of lung cancer, not all smokers develop lung cancer,
      and a fraction of lifelong non-smokers will die from lung cancer. Genetic host
      factors have recently been implicated to account for some of the observed
      differences in lung cancer susceptibility. Various DNA alterations can be caused
      by exposure to environmental and endogenous carcinogens. Most of these
      alterations, if not repaired, may result in genetic instability, mutagenesis and
      cell death. DNA repair mechanisms are important for maintaining DNA integrity and
      preventing carcinogenesis. Recent genetic association studies on lung cancer risk
      have focused on identifying effects of single nucleotide polymorphisms (SNPs) in
      candidate genes, among which DNA repair genes are increasingly studied. Genetic
      variations in DNA repair genes are thought to modulate DNA repair capacity and
      are suggested to be related to lung cancer risk. We identified a sufficient
      number of epidemiologic studies on lung cancer to conduct a meta-analysis for
      genetic polymorphisms in nucleotide base repair (BER) pathway, focusing on 8
      oxoguanine DNA glycosylase 1, X-ray cross-complementing group 1 (XRCC1) and
      apurinic/apyrimidinic endonuclease 1. The 399Gln/Gln genotype of the XRCC1
      Arg399Gln polymorphism was associated with an increased risk of lung cancer among
      Asians (OR=1.34, 95% CI=1.16-1.54) but not among Caucasians. Little evidence of
      associations has been found between other BER genes and lung cancer risk.
      Considering the data available, it can be conjectured that if there is any risk
      association between single SNP and lung cancer, this risk increase/decrease will
      probably be minimal. Advances in identification of new polymorphisms and in high
      throughput genotyping techniques will facilitate analysis of multiple genes in
      multiple DNA repair pathways. Therefore, it is likely that the defining feature
      of future epidemiologic studies will be the simultaneous analysis of large
      samples of cases and controls.

PMID- 16982114
TI  - Identification of management units using population genetic data.
AB  - The identification of management units (MUs) is central to the management of
      natural populations and is crucial for monitoring the effects of human activity
      upon species abundance. Here, we propose that the identification of MUs from
      population genetic data should be based upon the amount of genetic divergence at
      which populations become demographically independent instead of the current
      criterion that focuses on rejecting panmixia. MU status should only be assigned
      when the observed estimate of genetic divergence is significantly greater than a
      predefined threshold value. We emphasize the need for a demographic
      interpretation of estimates of genetic divergence given that it is often the
      dispersal rate of individuals that is the parameter of immediate interest to
      conservationists rather than the historical amount of gene flow.

PMID- 16982115
TI  - Cloning, functional identification and structural modelling of Vitis vinifera S
      adenosylmethionine decarboxylase.
AB  - In this paper we report the cloning and full sequencing of S-adenosylmethionine
      decarboxylase (SAMDC, EC 4.1.1.50) cDNA from Vitis vinifera L. (VV) leaves, an
      enzyme belonging to the polyamine biosynthetic pathway, which appears to play an
      important role in the regulation of plant growth and development. The presence of
      two overlapping ORFs (tiny ORF and small ORF) upstream of the main ORF is
      reported in the Vitis cDNA. When the Vitis SAMDC cDNA was expressed in yeast
      without the two upstream ORFs, the resulting activity was about 50 times higher
      than the activity obtained with the full cDNA. These results demonstrated the
      strong regulatory activity of the tiny and small ORFs. RT-PCR expression analysis
      showed evidence of a similar mRNA level in all the tissues tested, with the
      exception of the petioles. The VV SAMDC was also modelled using its homologues
      from Solanum tuberosum and Homo sapiens as template. The present work confirmed,
      for the first time in a woody plant of worldwide economic interest such as
      grapevine, the presence of a regulatory mechanism of SAMDC, enzyme that has a
      well-established importance in the modulation of plant growth and development.

PMID- 16982116
TI  - Developmental regulation of water uptake in wheat.
AB  - The discovery of aquaporins has provided a new basis for studying and
      interpreting water relations in plants. However, slow progress has been made in
      elucidating the functional facets of the aquaporin-mediated water pathway in
      whole plant systems. While increasing experimental evidence suggests that these
      proteins are directly involved in mediating water homeostasis at varying
      environmental conditions, only a few attempts have been made to understand their
      contribution to overall water transport at different developmental stages. By
      using a chemical inhibitor (HgCl(2)) of aquaporins function, here we present in
      planta evidence for both diurnal and developmental regulation of aquaporin
      activity in wheat. We demonstrate that the greatest sensitivity of water flux to
      pharmacological blockage occurs at the stage of ear emergence and does not
      coincide with the phenological stage at which the greatest plant water uptake
      occurs (milky ripeness). The relationship transpiration flux (Q) vs. soil-leaf
      water potential difference (DeltaPsi(soil-leaves)) revealed a gradual decrease of
      plant resistance to water flux from tillering to milky ripeness, both in HgCl(2)
      treated and untreated control plants. However, the mercury-inhibition of water
      flux began to gradually increase at ear emergence, suggesting that a larger
      portion of water moves through aquaporins from this developmental stage on.
      Although the intercept of the DeltaPsi(soil-leaves)/Q regression line, i.e. the
      DeltaPsi required to initiate the water flux through the soil-plant-air
      continuum, was generally not affected by mercury treatment, a significant mercury
      effect on the intercept was observed at the stage of ear formation. These
      findings may have important implications for predicting which strategy plants
      utilize to optimize water use during their life cycle.

PMID- 16982117
TI  - [Aspergillosis in systemic diseases treated with steroids and/or
      immunosuppressive drugs: report of 9 cases and review of the literature].
AB  - This is a multicentric retrospective study of aspergillosis in patients treated
      by corticosteroids and/or immunosuppressive drugs for systemic diseases and a
      review of the literature. Nine patients, 5 men and 4 women, mean age of 62.8
      years old were included among which Horton's diseases (3 cases), systemic lupus
      erythematosus (2), polymyositis (1), microscopic polyangiitis (1), idiopathic
      thrombocytopenic purpura (1), rheumatoid polyarthritis (1). Aspergillosis
      occurred in average 28.4 month after the diagnosis of systemic disease, and 28
      months after the beginning of its treatment: corticosteroids in all cases, at a
      dose of 50.8 mg/day (equivalent prednisone) in average, cyclophosphamide (2
      cases), methotrexate (1), intravenous immunoglobulins (1), leflunomide (1). All
      cases were invasive or chronic pulmonary aspergillosis located in the lungs (6
      cases), or in the brain (3). Revealing symptoms were mild and non specific.
      Lymphopenia was severe in most cases, in average 472 lymphocytes/mm3 and 283
      CD4+/mm3. The diagnosis was confirmed 20.75 days after the first symptoms in
      invasive aspergillosis, and 18.5 months in the chronic pulmonary cases, by
      cultures in 7 cases (broncho-alveolar lavage: 4; cerebral biopsy: 3), and direct
      microscopy examination of broncho-alveolar lavage in 2 cases. Specific serology
      was positive in 4 cases. Patients were treated by voriconazole (4 cases),
      itraconazole (2), amphotericin B (1), association of caspofungin and voriconazole
      (1), successive voriconazole and itraconazole (1). Six patients recovered from
      aspergillosis with 10.8 months of following time, 3 patients died a few days
      after confirmation of the diagnosis. Fifty-four cases of the literature are
      analysed.

PMID- 16982118
TI  - Contamination of the southern Baltic Sea with 137Cs and 90Sr over the period 2000
      2004.
AB  - Changes of the (137)Cs activity concentrations in the southern Baltic Sea waters
      were investigated over the period 2000-2004 and distribution of the (90)Sr
      concentrations was determined in 2004. In the discriminated period further
      decrease of (137)Cs concentrations was observed. The average activity
      concentration of (137)Cs declined from 59.4Bq/m(3) in 2000 to 45.1Bq/m(3) in
      2004. The greatest changes of (137)Cs activities occurred in 2003 as a
      consequence of the medium-size inflow of a saline waters from the North Sea. This
      inflow affected (137)Cs activities as well as its distribution in the Baltic Sea.
      Changes in (90)Sr activity concentrations proceeded at much slower rate. The
      average activity concentration of (90)Sr was equal to 8.7Bq/m(3) in 2004. The
      annual fluvial (137)Cs fluxes from the Vistula river were also estimated. In
      2000, the (137)Cs load from Vistula was of an order of 0.15TBq/year, and in 2004
      0.05TBq/year.

PMID- 16982119
TI  - ELISA method for monitoring human serum IgE specific for Cry1Ab introduced into
      genetically modified corn.
AB  - Enzyme-linked immunosorbent assay (ELISA) is the most convenient method of
      monitoring the occurrence of IgE antibodies specific for novel proteins in
      genetically modified (GM) foods. The levels of IgE specific for a recombinant
      protein, Cry1Ab, were determined using an ELISA method. A soluble form of the
      Cry1Ab protein purified from pCold1 vector-transformed Escherichia coli
      pTf16/BL21 was used as the ELISA coating antigen, and 1M NaCl was used as the
      washing buffer to remove IgE non-specifically bound to the coated antigen. Sera
      from 44 patients allergic to major food allergens were obtained, diluted 20-fold,
      tested, and found no identifiable IgE above background levels. We also tested
      sera from patients with corn allergy against whole extracts of non-GM and GM-corn
      (MON 810) using immunoblotting. The staining patterns were similar for the two
      types of corn. These results indicate that significant levels of IgE antibodies
      specific to Cry1Ab were not found in the sera of Japanese patients with food
      allergies.

PMID- 16982120
TI  - Health technology adoption and the politics of governance in the UK.
AB  - The manner in which clinical and cost-effectiveness data are used to inform
      decisions about the funding and availability of drugs, therapies and medical
      devices is inherently politicised within collectively financed systems of health
      care. The National Institute for Health and Clinical Excellence (NICE) was
      established by the British government in 1999 to reach evidence-based decisions
      on whether selected health technologies should be made available by the National
      Health Service in England and Wales. But NICE is also required to involve a broad
      range of interested parties in the decision-making process, provide detailed
      rationales for its rulings and defend appeals from aggrieved parties. Debates
      about the emergence of "deliberative" forms of policy governance--based upon
      participation by a broad range of stakeholders rather than reliance on
      scientific, bureaucratic or political expertise alone--are thus particularly
      apposite. This article draws on a study of decision-making within NICE by
      focusing upon the tenor and orientation of deliberation about the adoption of
      health technologies. Does such deliberation take place upon a level playing field
      for different interests? Or do implicit parameters and understandings in the
      deliberative process tend to privilege some interests by structuring debate and
      attendant outcomes? Findings suggest that deliberative assumptions and parameters
      pertaining to fluid and contestable ideas of transparent reasoning and domain
      competence both reflect and shape relationships of influence and marginality
      among participants. Broader analytical implications centre on a distinction
      between "deliberative democracy" and "democratic deliberation". The extent to
      which this distinction is acknowledged and addressed in policy and practise will
      have marked implications for the substantive nature of attempts to broaden
      involvement in decision-making within public sector bodies such as NICE.

PMID- 16982121
TI  - Correlation between drug treatment adherence and lithium treatment attitudes and
      knowledge by bipolar patients.
AB  - BACKGROUND: Non-adherence should always be investigated when there is a failure
      in bipolar treatments, since it is known that reported non-adherence rates in
      bipolar disorder treatment for long-term prophylactic pharmacotherapy range from
      18% to 52%, with a median prevalence of 44.7%. Several factors are related to the
      poor adherence and reduction of medication efficiency, such as the different
      types of bipolar disorder, the presence of side effects, medication interactions,
      level of patient's knowledge about the disorder and their attitude towards
      treatment, complexity of medical regimens and the doctor-patient relationship.
      METHODS: Bipolar disorder outpatients under lithium treatment from the Hospital
      de Clinicas and Materno Infantil Presidente Vargas of Porto Alegre were
      recruited. All the patients had bipolar disorder and gave informed consent to
      participate in a clinical interview (106), answered the Lithium Attitudes
      Questionnaire (LAQ), Lithium Knowledge Test (LKT), Medication Adherence Rating
      Scale (MARS) and had plasma and red blood cells lithium measurements to assess
      their medication adherence and the factors that influenced it. RESULTS: 85.6% of
      bipolar disorder were adherent to lithium treatment showing plasma lithium
      between 0.6 and 1.2 mmol/L. There was an inverted correlation between the total
      LAQ score with plasma and red blood cells, a positive correlation between LKT and
      MARS with plasma and red blood cell lithium. CONCLUSION: These results confirmed
      that knowledge level is directly correlated to treatment adherence and patients'
      attitudes, lower adherence, general opposition to prophylaxis, fear of side
      effects, denial of therapeutic effectiveness and illness severity.

PMID- 16982122
TI  - Pretreatment with pyridinium oximes improves antidotal therapy against tabun
      poisoning.
AB  - Oximes K033 [1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide] and K048
      [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide]
      were tested as pretreatment drugs in tabun-poisoned mice followed by treatment
      with atropine plus K033, K048, K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4
      carbamoylpyridinium) propane dibromide], TMB-4 [1,3-bis(4
      hydroxyiminomethylpyridinium) propane dibromide] and HI-6 [(1-(2
      hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane
      dichloride)]. Oxime doses of 25% or 5% of its LD(50) were used for pretreatment
      15 min before tabun-poisoning and for treatment 1 min after tabun administration
      to mice. The best therapeutic effect was obtained when oxime K048 (25% of its
      LD(50)) was used in both pretreatment and treatment with atropine. This regiment
      insured survival of all tested animals after the application of 10 LD(50) of
      tabun. In addition, since butyrylcholinesterase (BChE; EC 3.1.1.8) is considered
      an endogenous bioscavenger of anticholinesterase compounds and its interactions
      with oximes could be masked by AChE interactions, we evaluated kinetic parameters
      for interactions of tested oximes with native and tabun-inhibited human plasma
      BChE and compared them with results obtained previously for human erythrocyte
      acetylcholinesterase (AChE; EC 3.1.1.7). Progressive inhibition of BChE by tabun
      was slightly faster than that of AChE. The reactivation of tabun-inhibited BChE
      by oximes was very slow, and BChE binding affinity for oximes was lower than
      AChE's. Therefore, BChE could scavenge tabun prior to AChE inhibition, but fast
      oxime-assisted reactivation of tabun-inhibited AChE or protection of AChE by
      oxime against inhibition with tabun would not be obstructed by interaction
      between BChE and oximes.

PMID- 16982123
TI  - Effects of perinatal exposure to low doses of cadmium or methylmercury on thyroid
      hormone metabolism in metallothionein-deficient mouse neonates.
AB  - Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired
      neurodevelopment. Thyroid hormone is essential for normal brain development.
      However, the issue whether Cd or MeHg, especially at low doses, interrupts
      thyroid hormone action remains to be investigated. In the present study, effects
      of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism
      were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal
      mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from
      gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were
      collected from neonates on PND 10. Iodothyronine deiodinase activities and serum
      thyroxine (T4) concentrations were measured. MeHg exposure failed to induce
      changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2
      deiodinase (D2) activities regardless of the MT genotype. However, exposure to
      MeHg resulted in a decrease in brain type 3 deiodinase (D3) activity in MT-I/II
      null and wild-type neonates. In contrast, exposure to Cd resulted in a decrease
      in serum T4 levels in MT-I/II null neonates. Consistently, brain D2 activity was
      increased in Cd-exposed MT-I/II null neonates. No significant changes in liver D1
      and brain D3 activities were induced by Cd administration. Our study demonstrates
      that perinatal exposure to low doses of Cd or MeHg can induce changes in brain
      deiodinase activities in the neonates, suggesting that thyroid hormone metabolism
      in fetuses and neonates might be a potential target of Cd and MeHg.

PMID- 16982124
TI  - Monitoring intervention programmes for out-of-hospital cardiac arrest in a mixed
      urban and rural setting.
AB  - BACKGROUND: Only a few data are available on the survival rate following out-of
      hospital cardiac arrest in different Italian settings. We report an analysis of a
      10-year experience in a mixed rural/urban setting, the main variables associated
      with survival, and the preliminary results of the implementation of an automated
      external defibrillator (AED) programme operated by lay volunteers on the
      effectiveness of the existing Emergency Medical Service (EMS). METHODS: We report
      data from an observational cohort study on all adults, resuscitated from
      witnessed cardiac arrest between 1994 and 2004 in the district area of Forli
      (Italy). The AED programme was introduced in 2002. Entry variables, time
      intervals and nodal events were tested according to Utstein recommendations. The
      predictors of favourable outcomes (Overall Performance Category 1-2) were
      identified by logistic regression analysis. RESULTS: The witnessed cardiac arrest
      rate was 27/100,000 population per year (95% confidence interval, 18-38). The
      initial rhythm was shockable in 241/479 cases (50.3%). After resuscitation, 55
      (11.5%) subjects had a favourable outcome at discharge and 38 (7.9%) at 1 year.
      Time-to-treatment was longer for EMS than for AED-equipped units (median, 8 min
      interquartile range, 6-10 (467 cases) versus 6 min interquartile range, 4-8 (13
      cases); P<0.013), but the final results of the AED programme were poor, with only
      1 subject saved/171,000 inhabitants in 2 years. Positive outcome predictors were
      male sex, younger age, shockable rhythms, low number of defibrillations, and no
      history of hypertension, diabetes, myocardial infarction or congestive heart
      failure. CONCLUSIONS: Even in a mixed urban/rural setting, survival from out-of
      hospital cardiac arrest is dependent on well-known predictors. In our setting,
      the number of cases saved by an AED programme is limited when accompanied by an
      efficient traditional EMS. The allocation of resources to an AED programme should
      be reconsidered in a mixed rural/urban setting.

PMID- 16982125
TI  - Radiological assessment of the adult chest: implications for chest compressions.
AB  - The recommended depth for chest compression during adult cardiopulmonary
      resuscitation (CPR) is 4-5 cm, and for children one-third the anterior-posterior
      (AP) chest diameter. A compression depth of one-third of the AP chest diameter
      has also been suggested for adult CPR. We have assessed chest CT scans to measure
      what proportion of the adult AP chest diameter is compressed during CPR.
      Measurements of AP diameter of chest CT scans were taken from the skin anteriorly
      at the middle of the lower half of the sternum, perpendicularly to the skin on
      the posterior thorax. The anatomical structure that would be compressed at this
      level was also noted. One hundred consecutive CT scans were examined (66 males
      and 34 females). The age (mean +/- S.D.) was 68+/-12 years. AP chest diameter was
      253 +/- 27 mm for males and 235 +/- 30 mm for females. The proportion of total AP
      chest diameter compressed with current compressions is 15.8-19.8% for males and
      17.0-21.3% for females. The commonest anatomical structures that would be
      compressed are the ascending aorta (38%) and the top of the left atrium (36%).
      There is also a wide anatomical variation in the shape of the adult chest. A
      chest compression depth of 4-5 cm in adults equates to approximately one-fifth of
      the AP diameter of the adult chest.

PMID- 16982126
TI  - Androstenetriol improves survival in a rodent model of traumatic shock.
AB  - Trauma results in activation of the hypothalamic-pituitary-adrenal axis to
      mediate a cascade of neurohormonal changes as a defensive mechanism. Its
      prolongation, however, leads to a hypermetabolic, hypoperfused, and
      immunosuppressed state, setting the stage for subsequent sepsis and organ
      failure. Androstenetriol (5-androstene-3beta, 7beta, 17betatriol - AET), a
      metabolite of dehydroepiandrosterone, up-regulates the host immune response
      markedly, prevents immune suppression and controls inflammation, leading to
      improved survival after lethal infections by several diverse pathogens and lethal
      radiation. Such actions may be useful in improving survival from traumatic shock.
      HYPOTHESIS: The neurosteroid AET will increase survival following traumatic
      shock. METHODS: A combat relevant model of traumatic shock was used. Male Sprague
      Dawley rats were anesthetized, catheterized and subjected to soft tissue injury
      (laparotomy). Animals were allowed to regain consciousness over the next 0.5 h
      and then bled 40% of their blood volume over 15 min. Forty-five minutes after the
      onset of hemorrhage animals were randomized to receive either a single
      subcutaneous dose of AET (40 mg/kg, sc) or vehicle (methylcellulose). Volume
      resuscitation consisted of l-lactated Ringer's (three times the shed blood
      volume), followed by packed red blood cells (one-third shed red cell volume).
      Animals were observed for three days. RESULTS: A total of 24 animals were
      studied. Of the 12 animals randomized to receive AET, all (100%) survived
      compared to 9 of 12 animals (75%) randomized to receive the vehicle (p < 0.05).
      CONCLUSION: AET significantly improved survival when administered subcutaneously
      in a single dose in this rodent model of traumatic shock. Further survival and
      mechanism studies are warranted.

PMID- 16982127
TI  - Effects of compression depth and pre-shock pauses predict defibrillation failure
      during cardiac arrest.
AB  - BACKGROUND: Cardiopulmonary resuscitation (CPR) and electrical defibrillation are
      the primary treatment options for ventricular fibrillation (VF). While recent
      studies have shown that providing CPR prior to defibrillation may improve
      outcomes, the effects of CPR quality remain unclear. Specifically, the clinical
      effects of compression depth and pauses in chest compression prior to
      defibrillation (pre-shock pauses) are unknown. METHODS: A prospective, multi
      center, observational study of adult in-hospital and out-of-hospital cardiac
      resuscitations was conducted between March 2002 and December 2005. An
      investigational monitor/defibrillator equipped to measure compression
      characteristics during CPR was used. RESULTS: Data were analyzed from 60
      consecutive resuscitations in which a first shock was administered for VF. The
      primary outcome was first shock success defined as removal of VF for at least 5s
      following defibrillation. A logistic regression analysis demonstrated that
      successful defibrillation was associated with shorter pre-shock pauses (adjusted
      odds ratio 1.86 for every 5s decrease; 95% confidence interval 1.10-3.15) and
      higher mean compression depth during the 30s of CPR preceding the pre-shock pause
      (adjusted odds ratio 1.99 for every 5mm increase; 95% confidence interval 1.08
      3.66). CONCLUSIONS: The quality of CPR prior to defibrillation directly affects
      clinical outcomes. Specifically, longer pre-shock pauses and shallow chest
      compressions are associated with defibrillation failure. Strategies to correct
      these deficiencies should be developed and consideration should be made to
      replacing current-generation automated external defibrillators that require long
      pre-shock pauses for rhythm analysis.

PMID- 16982128
TI  - From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to
      wants.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis is the critical mediator of the
      vertebrate stress response system, responding to environmental stressors by
      maintaining internal homeostasis and coupling the needs of the body to the wants
      of the mind. The HPA axis has numerous complex drivers and highly flexible
      operating characterisitics. Major drivers include two circadian drivers, two
      extra-hypothalamic networks controlling top-down (psychogenic) and bottom-up
      (systemic) threats, and two intra-hypothalamic networks coordinating behavioral,
      autonomic, and neuroendocrine outflows. These various networks jointly and
      flexibly control HPA axis output of periodic (oscillatory) functions and a range
      of adventitious systemic or psychological threats, including predictable daily
      cycles of energy flow, actual metabolic deficits over many time scales, predicted
      metabolic deficits, and the state-dependent management of post-prandial responses
      to feeding. Evidence is provided that reparation of metabolic derangement by
      either food or glucocorticoids results in a metabolic signal that inhibits HPA
      activity. In short, the HPA axis is intimately involved in managing and
      remodeling peripheral energy fluxes, which appear to provide an unidentified
      metabolic inhibitory feedback signal to the HPA axis via glucocorticoids. In a
      complementary and perhaps a less appreciated role, adrenocortical hormones also
      act on brain to provide not only feedback, but feedforward control over the HPA
      axis itself and its various drivers, as well as coordinating behavioral and
      autonomic outflows, and mounting central incentive and memorial networks that are
      adaptive in both appetitive and aversive motivational modes. By centrally
      remodeling the phenotype, the HPA axis provides ballistic and predictive control
      over motor outflows relevant to the type of stressor. Evidence is examined
      concerning the global hypothesis that the HPA axis comprehensively induces
      integrative phenotypic plasticity, thus remodeling the body and its governor, the
      brain, to yoke the needs of the body to the wants of the mind. Adverse side
      effects of this yoking under conditions of glucocorticoid excess are discussed.

PMID- 16982129
TI  - Language and cortical function: conceptual developments.
AB  - Mastery of a language is a capacity that distinguishes humans from other animals.
      Attempts to identify the brain functions that are necessary for the possession of
      linguistic skills began in the 19th century with the research of Broca and
      Wernicke. We trace the principal experimental developments since then, ranging
      from psychological studies of aphasic patients to non-invasive brain-imaging
      investigations. The development of theories concerning word recognition, reading
      aloud, fluent speech and understanding utterances are described. Possible brain
      regions involved in these abilities, identified by means of non-invasive imaging,
      are considered. We examine the various claims made by these researchers as to
      what their experiments show and in particular examine the validity of their
      theories. This conceptual analysis shows that in many cases the interpretation of
      experiments is confused and that the theories elaborated are not tenable. We seek
      to clarify what can be substantiated concerning the workings of the brain and the
      exercise of linguistic skills.

PMID- 16982130
TI  - Non-obstetrical acute abdomen during pregnancy.
AB  - Acute abdomen in pregnancy remains one of the most challenging diagnostic and
      therapeutic dilemmas today. The incidence of acute abdomen during pregnancy is 1
      in 500-635 pregnancies. Despite advancements in medical technology, preoperative
      diagnosis of acute abdominal conditions is still inaccurate. Laboratory
      parameters are not specific and often altered as a physiologic consequence of
      pregnancy. Use of laparoscopic procedures as diagnostic tools makes diagnosis of
      such conditions earlier, more accurate, and safer. Appendicitis is the most
      common cause of the acute abdomen during pregnancy, occurring with a usual
      frequency of 1 in 500-2000 pregnancies, which amounts to 25% of operative
      indications for non-obstetric surgery during pregnancy. Surgical treatment is
      indicated in most cases, as in nonpregnant women. Laparoscopic procedures in the
      treatment of acute abdomen in pregnancy proved safe and accurate, and in selected
      groups of patients are becoming the procedures of choice with a perspective for
      the widening of such indications with more frequent use and subsequent optimal
      results. Despite these advances, laparotomy still remains the procedure of choice
      in complicated and uncertain cases.

PMID- 16982131
TI  - Administration of the anabolic androgenic steroid nandrolone decanoate to female
      rats causes alterations in the morphology of their uterus and a reduction in
      reproductive capacity.
AB  - OBJECTIVE: The aim of the present investigation was to characterize the effects
      of supraphysiological doses of the anabolic androgenic steroid nandrolone
      decanoate (ND) on the fertility of female rats, as well as on the morphology of
      their uterus. STUDY DESIGN: Female Wistar rats (n=15) received a subcutaneous
      injection of ND (15 mg/kg) once daily during a 2-week period, while the control
      animals (n=10) were administered vehicle alone (arachidis oleum) in the same
      manner. Estrus behavior was evaluated 4 weeks after termination of this treatment
      and in cases where signs of receptivity were present, the female rat was given
      the opportunity to copulate with a male. After breeding, the female animals were
      sacrificed and their uteri examined histomorphologically. RESULTS: All ND-treated
      animals exhibited abnormal vaginal smears, whereas all of the control smears were
      normal. Most (73%) of the treated females demonstrated normal estrus behavior
      (i.e., willingness) on the day of mating, but none got pregnant; whereas all of
      the control rats became pregnant. The female rats receiving the ND showed an
      enhanced rate of weight gain and the myometrium thickness of their uteri was
      significantly increased, while the endometrium was significantly thinner.
      Furthermore, ND caused a significant proportion of the treated animals to display
      tortuous and irregularly branching endometrial glands, as well as a lack of the
      physiologically normal infiltration of eosinophilic leukocytes into the
      endometrium (endometrial eosinophilic homing), a finding that has not been
      reported previously. CONCLUSION: The present findings indicate that high doses of
      ND cause morphological and physiological alterations in the uterus of female rats
      that are associated with a suppression of their reproductive capacity.

PMID- 16982132
TI  - Developing the interaction matrix technique as a tool assessing the impact of
      traffic on air quality.
AB  - This paper develops a technique which can be used as a preliminary tool for
      assessing air quality related to urban traffic. It combines a Geographic
      Information System (GIS) with an interaction matrix-type methodology based on a
      system analysis approach. The matrix identifies and quantifies interactions
      between all selected variables involved in a system as well as their interaction
      with the system as a whole. This matrix is used to determine the weightings to
      apply to spatial datasets within a GIS to develop a pollution vulnerability map.
      The focus of the paper is to introduce and assess a more versatile coding of the
      interaction matrix with respect to previously used coding. A case study is
      presented in which the modified interaction methodology is applied to data for a
      busy urban location. The resulting vulnerability map, in terms of pollution
      vulnerable hot spots, was compared to a pollution map derived from an advanced
      dispersion model. The interaction matrix technique with GIS can be used as a tool
      complementary to sophisticated numerical modelling and has potential as an
      analytical tool to evaluate multidisciplinary systems.

PMID- 16982134
TI  - Monitoring and information reporting for sustainable forest management: a
      regional comparison of forestry stakeholder perceptions.
AB  - Since the United Nations Conference on Environment and Development (UNCED) [1992,
      Agenda 21: programme of action for sustainable development. United Nations
      Conference on Environment and Development (UNCED), 3-14 June 1992. Rio de
      Janeiro, Brazil, 294pp.], the management of information has become central to the
      management of forest resources. In the cases of North America and Europe, similar
      issues have been challenging policy makers as they determine the information
      suitable for monitoring progress towards sustainable forest management (SFM).
      Using an 'online' survey, this research explored multiple stakeholder
      perspectives on monitoring and information reporting for SFM in different
      jurisdictions. The research was based on the premise that an analysis of the
      variation in stakeholder observations across a range of SFM 'issue areas' could
      provide valuable insight into the perceived need for SFM-related monitoring and
      information reporting in the regions of Europe, Canada and the USA. Despite the
      traditional limitations associated with exploratory survey research, the results
      indicate a demand for more information on SFM-related issues. The results also
      highlight the degree to which the perceptions of a sample of stakeholders can
      differ between Europe, USA and Canada. While these results cannot be generalized
      beyond the present study, they do suggest that further studies are needed to
      understand stakeholder perspectives on forestry-related monitoring and
      information reporting in different jurisdictions.

PMID- 16982133
TI  - Partial neutralization of rain by seaspray: the case of Reconcavo, Bahia-Brazil.
AB  - In the Reconcavo of Bahia (located between 12 degrees 33' and 13 degrees 10'S and
      38 degrees 00'and 39 degrees 00'W), there are significant discharges of SO(2) and
      NO(x) due to local, industrial and urban activities. The incoming air masses from
      the Atlantic Ocean are enriched with seaspray, which neutralizes part of the rain
      acidity. The extent of seaspray neutralization of rain acidity was quantified in
      four sites of the region, each with different loads of seaspray. Rain samples
      were obtained daily at the same time, integrating the precipitation of the
      previous 24h, using wet-only collectors and analyzed for pH by potentiometry and
      for sodium by flame photometry. The amount of rain acidity in Reconcavo
      neutralized by seaspray ranged from <1% up to 88% and depended on the site. On
      average, neutralization ranged from 5% to 18%.

PMID- 16982135
TI  - Economics of "essential use exemptions" for metered-dose inhalers under the
      Montreal Protocol.
AB  - The Montreal Protocol on Substances that Deplete the Ozone Layer has led to rapid
      reductions in the use of ozone-depleting substances worldwide. However, the
      Protocol provides for "essential use exemptions" (EUEs) if there are no
      "technically and economically feasible" alternatives. An application that might
      qualify as an "essential use" is CFC-powered medical metered-dose inhalers (MDIs)
      for the treatment of asthma and chronic obstructive pulmonary disease (COPD), and
      the US and other nations have applied for exemptions in this case. One concern is
      that exemptions are necessary to ensure access to medications for low-income
      uninsureds. We examine the consequences of granting or withholding such
      exemptions, and conclude that government policies and private-sector programs are
      available that make it economically feasible to phase out chlorofluorocarbons
      (CFCs) in this application, thereby furthering the global public health
      objectives of the Montreal Protocol without compromising the treatment of
      patients who currently receive medication by means of MDIs.

PMID- 16982136
TI  - Re: Michael Muntener, Brigitte Schurch, Bjorn Wefer and Andre Reitz. Systemic
      nitric oxide augmentation leads to a rapid decrease of the bladder outlet
      resistance in healthy men. Eur Urol 2006;50:112-117; discussion 117-118.

PMID- 16982137
TI  - Low-temperature preparation and microwave photocatalytic activity study of TiO2
      mounted activated carbon.
AB  - TiO2 thin films were deposited on granular activated carbon by a dip-coating
      method at low temperature (373 K), using microwave radiation to enhance the
      crystallization of titania nanoparticles. Uniform and continuous anatase titania
      films were deposited on the surface of activated carbon. BET surface area of TiO2
      mounted activated carbon (TiO2/AC) decreased a little in comparison with
      activated carbon. TiO2/AC possessed strong optical absorption capacity with a
      band gap absorption edge around 360 nm. The photocatalytic activity did not
      increase when the as-synthesized TiO2/AC was thermally treated, but was much
      higher than commercial P-25 in degradation of phenol by irradiation of
      electrodeless discharge lamps (EDLs).

PMID- 16982138
TI  - Experimental investigation of basic oxygen furnace slag used as aggregate in
      asphalt mixture.
AB  - Chinese researchers have commenced a great deal of researches on the development
      of application fields of basic oxygen steel making furnace slag (BOF slag) for
      many years. Lots of new applications and properties have been found, but few of
      them in asphalt mixture of road construction engineering. This paper discussed
      the feasibility of BOF steel slag used as aggregate in asphalt pavement by two
      points of view including BOF steel slag's physical and micro-properties as well
      as steel slag asphalt materials and pavement performances. For the former part,
      this paper mainly concerned the mechanochemistry and physical changes of the
      steel slag and studied it by performing XRD, SEM, TG and mercury porosimeter
      analysis and testing method. In the second part, this paper intended to use BOF
      steel slag as raw material, and design steel slag SMA mixture. By using
      traditional rutting test, soak wheel track and modified Lottman test, the high
      temperature stability and water resistance ability were tested. Single axes
      compression test and indirect tensile test were performed to evaluate the low
      temperature crack resistance performance and fatigue characteristic.
      Simultaneously, by observing steel slag SMA pavement which was paved
      successfully. A follow-up study to evaluate the performance of the experimental
      pavement confirmed that the experimental pavement was comparable with
      conventional asphalt pavement, even superior to the later in some aspects. All of
      above test results and analysis had only one main purpose that this paper
      validated the opinion that using BOF slag in asphalt concrete is feasible. So
      this paper suggested that treated and tested steel slag should be used in a more
      extensive range, especially in asphalt mixture paving projects in such an
      abundant steel slag resource region.

PMID- 16982139
TI  - Auto-refrigeration/brittle fracture analysis of existing olefins plants-
      translation of lessons learned to other processes.
AB  - This paper describes the use of process hazards analysis (PHA) techniques and
      "API 579 Recommended Practice for Fitness-for-Service, Assessment of Existing
      Equipment for Brittle Fracture" to evaluate existing olefins plants. It also
      examines some of the identified transient process excursions that can result in
      operations below vessel minimum allowable temperature (MAT), creating the
      potential for brittle fracture, and the methods of the evaluation are described.
      The importance of identifying transient process conditions and making materials
      of-construction selections based on these conditions is emphasized. Translation
      of the typical findings and lessons learned to other processes handling light
      liquid hydrocarbon materials in carbon steel equipment is discussed, as well as
      the importance of operator training and response.

PMID- 16982140
TI  - Polychlorinated naphthalenes and other chlorinated tricyclic aromatic
      hydrocarbons emitted from combustion of polyvinylchloride.
AB  - Chloronaphthalenes (CNs) and phenanthrenes or/and anthracenes (CP/CAs) were
      detected in the emissions of polyvinylchloride (PVC) combustion at 900 degrees C.
      The presence of metallic iron, copper, or aluminum increased the formation of
      highly chlorinated CNs (tri- to octachloro-homologues) in the PVC combustion
      process. Total levels of CNs and CP/CAs were 40-48 and 76-116 mg/kg PVC,
      respectively, in the emissions from combustion of PVC with metals.
      Monochloronaphthalenes, dichloronaphtahlenes, monochlorophenanthrenes, and
      monochloroanthracenes were the predominant homologues. The other CN homologues
      were minor combustion byproducts. Detection of CNs in the PVC combustion
      emissions suggests that CN formation from solid waste incineration is a source of
      CNs in the environment.

PMID- 16982141
TI  - Textural development of sugar beet bagasse activated with ZnCl2.
AB  - In this study, activated carbons were prepared from sugar beet bagasse, which is
      side product and waste in sugar plants, by chemical activation with ZnCl2.
      Influence of activation temperature was investigated on to pore structure.
      ZnCl2/sugar beet bagasse ratio (impregnation ratio) was selected as 1:1. The
      impregnated sample was raised to the activation temperature under N(2)
      (100ml/min) atmosphere with 10 degrees C/min heating rate and hold at this
      temperature for 1h. The activation temperature was varied over the temperature
      range of 400-900 degrees C. BET surface area values were determined in the range
      of 832-1697 m(2)/g. Under the experimental conditions, 500 degrees C was found to
      be the optimal condition for producing high surface area carbons with ZnCl2
      activation. Sugar beet bagasse was suitable for preparation of activated carbon
      with essentially microporous structure. Activated carbon ash content was found in
      the range of 1.2-2.7 (%w/w d.b.). Activated carbon samples and raw material were
      characterized by XRD, FT-IR, DTA and TGA.

PMID- 16982142
TI  - Batch kinetics and thermodynamics of chromium ions removal from waste solutions
      using synthetic adsorbents.
AB  - Mg(OH)(2) was identified as a component in the magnesia cement being adsorbent
      for Cr(VI). Modified magnesia cement was prepared by the addition of ferric
      chloride and humic acid. The equilibrium adsorption of Cr(VI) on magnesia cement
      adsorbents (MF5-1) and (MF5-2) was investigated as a function of contact time,
      adsorbent weight, solute concentration and temperature. Tests of different
      isotherms have shown that the adsorption data fit the Langmiur and Freundlich
      isotherms at 25+/-1 degrees C. The nature of the diffusion process responsible
      for adsorption of Cr(VI) on (MF5-1) and (MF5-2) adsorbents was discussed. The
      kinetics and mechanism of diffusion of Cr(VI) into (MF5-1) and (MF5-2) adsorbents
      from aqueous solution have been studied as a function of Cr(VI) concentrations
      and reaction temperatures. The adsorption of Cr(VI) on the MF5-1 and MF5-2
      adsorbents follows first-order reversible kinetics. The forward and backward
      constants, k(1) and k(2) have been calculated at different temperatures between
      10 and 50 degrees C. The heat of activation of the adsorption, DeltaH(*) and
      DeltaS(*) were calculated for Cr(VI) at 25 degrees C. The values of DeltaH(*)
      were found 18.1 and 10.7 kJ mol(-1) for MF5-1 and MF5-2, respectively, while
      entropy change, DeltaS(*), were found -106.8 and -118.6 J mol(-1)K(-1) for MF5-1
      and MF5-2, respectively. The study showed that pore diffusion is the rate
      determining step in the adsorption of Cr(VI) ions for MF5-1 and MF5-2. MF5-2 was
      found more efficient for Cr(VI) adsorption than MF5-1. Also Cr(VI) can be
      adsorbed on MF5-2, whereas Cr(III) cannot. So, the competitive adsorption of
      multi-metals onto the MF5-2 adsorbent was studied. The studies showed that this
      adsorbent can be used as an efficient adsorbent material for the removal of
      Cr(VI) from water and nuclear power plant coolant water.

PMID- 16982143
TI  - Photocatalytic degradation of methyl red by TiO2: comparison of the efficiency of
      immobilized nanoparticles versus conventional suspended catalyst.
AB  - The photocatalytic efficiency of supported TiO2 nanoparticles (mean size 6 nm),
      immobilized onto the inner walls of a cylindrical glass photoreactor was compared
      versus the performance of conventional TiO2 Degussa P25 catalyst. For this
      purpose the degradation of methyl red dye was used as evaluation test. The
      obtained results showed that the TiO2 Degussa P25 catalyst is more efficient than
      the supported nanoparticles. The poorer performance of the nanosized catalyst can
      be ascribed to the fact that the immobilization procedure turns out, in spite of
      the extremely high surface to volume ratio, in an overall reduction of active
      surface area available for target molecule adsorption, due to the low porosity of
      the supported catalyst layer. The kinetics of the investigated processes were
      monitored and a study on the reaction products and intermediates was carried out
      in order to evaluate possible difference in the reaction pathway in presence of
      immobilized nanoparticles versus suspended catalyst. The results demonstrate that
      the mechanisms of parent dye degradation in presence of supported TiO2
      nanoparticles are the same as those occurring in presence of TiO2 Degussa P25
      catalyst. The present work describe the results obtained on the feasibility of
      scaling up the colloidal nanocrystal-based photocatalysis experiment: the
      comparison with a well standardized degradation method performed with a known
      material can allow a realistic evaluation of the advantages and the limits of the
      investigated nanoparticle towards the ultimate technology transfer.

PMID- 16982144
TI  - Time-dependent increase in Nogo-A expression after focal cerebral ischemia in
      marmoset monkeys.
AB  - Nogo-A is a myelin-associated protein that has been shown to inhibit axonal
      sprouting after lesions to the CNS. Several studies have demonstrated that
      blocking the activity or expression of this inhibitor can induce structural and
      functional recovery after CNS lesions. However, there are limited and
      contradictory data on the expression of Nogo-A after CNS lesions. In the present
      study, marmoset monkeys received permanent occlusion of the middle cerebral
      artery (MCAo). Two, 3, or 4 months after the onset of injury brain sections were
      stained for Nogo-A protein. Two sham operated marmosets were included as a
      control. Nogo-A protein expression was quantified in white matter and grey matter
      in the areas adjacent to the lesion (or the equivalent areas in the intact side).
      At 2 months after injury, but not at 3 or 4 months, there was a significant
      increase in the number of oligodendrocytes that were Nogo-A immunopositive. This
      increase was observed in white matter structures that were adjacent to the lesion
      (e.g. corona radiate (CR)); but not in: white matter structures distal to the
      lesion (e.g. corpus callosum (CC)); cortical regions adjacent to the lesion;
      contralateral regions or in sham operated marmosets. These data suggest that Nogo
      A levels are significantly increased within oligodendrocytes in areas adjacent to
      the lesion up to 2 months following cerebral ischaemia. Future studies will
      determine whether this offers the opportunity to promote plasticity by targeting
      Nogo-A weeks or months following stroke.

PMID- 16982145
TI  - Effects of external feedback about body tilt: Influence on the Subjective
      Proprioceptive Horizon.
AB  - The present study investigated a cognitive aspect upon spatial perception, namely
      the impact of a true or false verbal feedback (FB) about the magnitude of body
      tilt on Subjective Proprioceptive Horizon (SPH) estimates. Subjects were asked to
      set their extended arm normal to gravity for different pitch body tilts up to 9
      degrees . True FB were provided at all body tilt angles, whereas false FB were
      provided only at 6 degrees backward and 6 degrees forward body tilts for half of
      the trials. Our data confirmed previous results about the egocentric influence of
      body tilt itself upon SPH: estimates were linearly lowered with forward tilts and
      elevated with backward tilts. In addition, results showed a significant effect of
      the nature of the external FB provided to the subjects. When subjects received a
      false FB inducing a 3 degrees forward bias relative to physical body tilt, they
      set their SPH consequently higher than when they received a false FB inducing a 3
      degrees backward bias. These findings clearly indicated that false cognitive
      information about body tilt might significantly modify the judgement of a
      geocentric direction of space, such as the SPH. This may have deleterious
      repercussions in aeronautics when pilots have to localize external objects
      relative to earth-based directions in darkened environments.

PMID- 16982146
TI  - Adult aggression during an initial social encounter: effects of neonatal anoxia
      and relation to juvenile open-field activity.
AB  - In male Long-Evans hooded rats, we examined: (1) combined effects of neonatal
      anoxia and novelty exposure on aggression during adulthood; (2) open-field
      activity before juvenility as a predictor for adult aggression. Litters of
      neonates were exposed to either 100% N2 gas (Anoxia) or room air (Control) for 25
      min on postnatal Day 1 (P1). Within each of the Anoxia and Control conditions,
      one half of the neonates were individually exposed to a non-home cage for 3 min
      daily during P2-21 (Novel: N(Anoxia)=15; N(Control)=13) while the other half
      remained in the home cage (Home: N(Anoxia)=15; N(Control)=13). Prior to the onset
      of juvenility (P25), open-field activity was measured during four 20-s trials. At
      the onset of adulthood (P100-101), we measured the occurrence of biting during
      four 5-min sessions of social interaction between pairs of rats. Neonatal anoxia
      and novelty exposure had contrasting effects on adult aggression with the former
      increasing aggression and the latter having no statistically significant effect.
      The open-field measures before the onset of juvenility were significantly
      correlated with the occurrence of biting behavior during adulthood, suggesting
      that activity in a novel environment observed very briefly in early life may
      serve as a predictor for adult aggression.

PMID- 16982147
TI  - Thapsigargin-induced apoptosis was prevented by glycogen synthase kinase-3
      inhibitors in PC12 cells.
AB  - Uncontrolled calcium stress has been linked causally to a variety of
      neurodegenerative diseases, including ischemia, excitotoxicity and Alzheimer's
      disease. Thapsigargin, which increases [Ca2+]i, induces apoptotic cell death
      (chromatin condensation and DNA fragmentation) accompanied by caspase-3
      activation in PC12 cells. We examined whether GSK-3 is involved in thapsigargin
      induced cell death by using GSK-3 inhibitors in PC12 cells. Cells treated with
      0.1 microM thapsigargin for 24h shrank. The injured cells underwent chromatin
      condensation and nuclear fragmentation, indicating apoptotic cell death. We
      assayed the effects of selective GSK-3 inhibitors, SB216763, azakenpaullone and
      alsteropaullone on thapsigargin-induced apoptosis. These inhibitors completely
      protected cells from thapsigargin-induced apoptosis. Alsterpaullone did not
      reduce the GRP78 protein expression induced by thapsigargin, suggesting that GSK
      3 activation is not involved in induction of GRP78. In addition, GSK-3 inhibitors
      inhibited caspase-3 activation accompanied by thapsigargin-induced apoptosis. We
      showed in this report that thapsigargin-induced apoptosis is prevented by GSK-3
      inhibitors, suggesting that thapsigargin induces caspase-dependent apoptosis
      mediated through GSK-3 activation in PC12 cells.

PMID- 16982148
TI  - Impact of low back pain on functional limitations, depressed mood and quality of
      life in patients with rheumatoid arthritis.
AB  - Low back pain (LBP) and rheumatoid arthritis (RA) are common orthopedic problems,
      but there is little information on the importance of LBP in RA patients. The aim
      of this study was to investigate how LBP affects functional limitations,
      depressed mood, and quality of life in patients with RA. A complex questionnaire
      was answered by 281 RA patients, including questions about their RA and their
      experience of LBP. Functional limitations were assessed using the Hannover
      Activities of Daily Living questionnaire (ADL), depressed mood using the Center
      for Epidemiological Studies Depression Scale (CES-D) and health-related quality
      of life using the Short Form 12 health questionnaire (SF-12). The prevalence of
      LBP in RA patients was 53.4%. RA patients with LBP displayed a significantly
      higher degree of disability and depression than RA patients without LBP. There
      were no differences between the two groups with regard to the duration of RA, the
      number of operations or medication. LBP is an important factor for the physical
      and psychological behavior of RA patients. Therefore, the onset of LBP should not
      be overlooked or underestimated.

PMID- 16982149
TI  - Energy dissipation and dynamic response of an amplitude-modulation atomic-force
      microscopy subjected to a tip-sample viscous force.
AB  - In a common environment of atomic force microscopy (AFM), a damping force occurs
      between a tip and a sample. The influence of damping on the dynamic response of a
      cantilever must be significant. Moreover, accurate theory is very helpful for the
      interpretation of a sample's topography and properties. In this study, the
      effects of damping and nonlinear interatomic tip-sample forces on the dynamic
      response of an amplitude-formulation AFM are investigated. The damping force is
      simulated by using the conventional Kelvin-Voigt damping model. The interatomic
      tip-sample force is the attractive van der Waals force. For consistance with real
      measurement of a cantilever, the mathematical equations of the beam theory of an
      AM-AFM are built and its analytical solution is derived. Moreover, an AFM system
      is also simplified into a mass-spring-damper model. Its exact solution is simple
      and intuitive. Several relations among the damping ratio, the response ratio, the
      frequency shift, the energy dissipation and the Q-factor are revealed. It is
      found that the resonant frequencies and the phase angles determined by the two
      models are almost same. Significant differences in the resonant quality factors
      and the response ratios determined by using the two models are also found.
      Finally, the influences of the variations of several parameters on the error of
      measuring a sample's topography are investigated.

PMID- 16982150
TI  - The pathogenesis of anaemia in goats experimentally infected with Trypanosoma
      congolense or Trypanosoma brucei: use of the myeloid:erythroid ratio.
AB  - The present study examined the development of anaemia in Small East African goats
      experimentally infected with Trypanosoma congolense or Trypanosoma brucei.
      Experimental goats received a primary trypanosome challenge on day 0, treated
      with diminazene aceturate on day 49 and received a secondary trypanosome
      challenge on day 77 of the 136-day experiment. Both primary and secondary
      challenges were characterised by reduced peripheral erythrocyte counts, fall in
      packed cell volume (PCV), hypohaemoglobinaemia and reductions in the
      myeloid:erythroid ratios (M:E) compared with the uninfected goats. The
      progressive reduction in the M:E ratios denoted increased erythrogenesis in
      response to increased destruction of erythrocytes in blood by infecting
      trypanosomes or their products. The more rapid fall in M:E ratio in T. congolense
      infections shows that this parasite causes more severe clinical pathological
      effects in goats than T. brucei.

PMID- 16982151
TI  - Biologic and genetic comparison of Toxoplasma gondii isolates in free-range
      chickens from the northern Para state and the southern state Rio Grande do Sul,
      Brazil revealed highly diverse and distinct parasite populations.
AB  - The prevalence of Toxoplasma gondii in 84 free-range chickens (34 from the
      northern Para state, and 50 from Rio Grande do Sul, the southern state) from
      Brazil, South America was determined. Antibodies to T. gondii were assayed by the
      modified agglutination test (MAT), and found in 39 (46.4%) of 84 chickens with
      titers of 1:10 in one, 1:20 in two, 1:40 in four, 1:80 in seven, 1:160 in five,
      1:320 in six, 1:640 in eight and > or =1:1280 in six. Hearts and brains of 45
      chickens with titers of 1:20 or less were pooled and fed to two T. gondii-free
      cats. Hearts and brains of 39 chickens with titers of 1:10 or higher were
      bioassayed in mice. Feces of cats were examined for oocysts. One cat fed tissues
      from 31 chickens with titers of less than 1:10 from Rio Grande do Sul shed T.
      gondii oocysts. T. gondii was isolated by bioassay in mice from 33 chickens with
      MAT titers of 1:20 or higher. All infected mice from 10 isolates died of
      toxoplasmosis. All 34 isolates (15 from Para, 19 from Rio Grande do Sul) were
      genotyped using 11 genetic markers including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8,
      c29-2, L358, PK1, a new SAG2 and Apico. Eleven genotypes were revealed for Para
      isolates and seven genotypes for Rio Grande do Sul. No genotype was shared
      between the two geographical locations. These data suggest that T. gondii
      isolates are highly diverse and genetically distinct between the two different
      regions in Brazil that are 3500 km apart.

PMID- 16982152
TI  - Trichinella zimbabwensis in wild reptiles of Zimbabwe and Mozambique and farmed
      reptiles of Ethiopia.
AB  - In 1995, a new species of Trichinella (Trichinella zimbabwensis) was discovered
      in farmed Nile crocodiles (Crocodylus niloticus) in Zimbabwe, where the mode of
      transmission was the consumption of the meat of slaughtered crocodiles, used as
      feed. To determine whether T. zimbabwensis affects poikilotherm vertebrates in
      the wild, monitor lizards (Varanus niloticus) and Nile crocodiles were collected
      in Zimbabwe and Mozambique. In 5 (17.6%) of the 28 monitor lizards from Zimbabwe,
      T. zimbabwensis larvae were identified. For the wild Nile crocodiles from
      Mozambique, species-level identification was not possible, yet
      immunohistochemical analysis revealed that 8 (20%) of the 40 animals harboured
      non-encapsulated Trichinella sp. larvae, which probably belonged to T.
      zimbabwensis. This is the first report of T. zimbabwensis in wild reptiles, and
      the findings are consistent with reports that vertebrates with scavenger and
      cannibalistic behaviour are the most important hosts of Trichinella spp. The wide
      distribution of monitor lizards and crocodiles in Africa and the development of
      national crocodile breeding programs in many African countries should be taken
      into consideration when evaluating the risk of transmission of this parasite to
      mammals, including humans.

PMID- 16982153
TI  - Inhibition of krr1 gene expression in Giardia canis by a virus-mediated
      hammerhead ribozyme.
AB  - Giardia, a most primitive eukaryote, infects several species including human and
      it is a major agent of waterborne outbreak of diarrhea. It has been difficult to
      employ standard genetic methods in the study of Giardia, but the RNA virus-based
      transfection system has been developed and used for the genetic manipulation.
      KRR1 protein is responsible for ribosome biosynthesis in Giardia. In this study,
      cDNA encoding hammerhead ribozyme flanked with various lengths of antisense Krr1
      RNA were cloned into a viral vector pGCV634/GFP/GCV2174 derived from the genome
      of Giardia canis virus (GCV). RNA transcripts of the plasmids showed high
      cleavage activities on Krr1 mRNA in vitro. They were electroporated into GCV
      infected G. canis trophozoites and Krr1 mRNA level was decreased by 72% with the
      ribozyme KRzS and 86% with the ribozyme KRzL, while the control ribozyme TRzS
      showed no effect on the level of Krr1 mRNA. The two hammerhead ribozyme
      transfected cells grew slowly, their internal structures got blurred and the
      cells were deformed. These results indicated that GCV could be useful tool for
      gene manipulation of G. canis.

PMID- 16982154
TI  - Attenuation of beta-amyloid induced toxicity by sialic acid-conjugated
      dendrimeric polymers.
AB  - beta-amyloid (Abeta) is the primary protein component of senile plaques in
      Alzheimer's disease and is believed to be associated with neurotoxicity in the
      disease. We and others have shown that Abeta binds with relatively high affinity
      to clustered sialic acid residues on cell surfaces and that removal of cell
      surface sialic acids attenuate Abeta toxicity. In the current work, we have
      prepared sialic acid conjugated dendrimeric polymers and assessed the ability of
      these sialic acid conjugated dendrimers to prevent Abeta toxicity. Flow cytometry
      was used to analyze viability of SH-SY5Y neuroblastoma cells and the effects of
      soluble and clustered sialic acid mimics on Abeta cell toxicity. Soluble sialic
      acid attenuation of Abeta induced toxicity was effective only at high sialic acid
      concentrations and low Abeta concentration. The sialic acid conjugated
      dendrimeric polymers were able to attenuate Abeta toxicity at micromolar
      concentrations, or approximately three orders of magnitude lower concentrations
      than the soluble sialic acid. The toxicity prevention properties of the sialic
      acid modified dendrimers were a function of dendrimer size. This work may lead to
      the development of new classes of therapeutics for the prevention of Abeta
      toxicity.

PMID- 16982155
TI  - Biochemical characterization of a low molecular weight aspartic protease
      inhibitor from thermo-tolerant Bacillus licheniformis: kinetic interactions with
      Pepsin.
AB  - The present article reports a low molecular weight aspartic protease inhibitor,
      API, from a newly isolated thermo-tolerant Bacillus licheniformis. The inhibitor
      was purified to homogeneity as shown by rp-HPLC and SDS-PAGE. API is found to be
      stable over a broad pH range of 2-11 and at temperature 90 degrees C for 2 1/2h.
      It has a Mr (relative molecular mass) of 1363 Da as shown by MALDI-TOF spectra
      and 1358 Da as analyzed by SDS-PAGE . The amino acid analysis of the peptide
      shows the presence of 12 amino acid residues having Mr of 1425 Da. The secondary
      structure of API as analyzed by the CD spectra showed 7% alpha-helix, 49% beta
      sheet and 44% aperiodic structure. The Kinetic studies of Pepsin-API interactions
      reveal that API is a slow-tight binding competitive inhibitor with the IC(50) and
      Ki values 4.0 nM and (3.83 nM-5.31 nM) respectively. The overall inhibition
      constant Ki* value is 0.107+/-0.015 nM. The progress curves are time-dependent
      and consistent with slow-tight binding inhibition: E+I -->/<-- (k(4), k(5)) EI -
      >/<-- (k(6), k(7)) EI*. Rate constant k(6)=2.73+/-0.32 s(-1) reveals a fast
      isomerization of enzyme-inhibitor complex and very slow dissociation as proved by
      k(7)=0.068+/-0.009 s(-1). The Rate constants from the intrinsic tryptophanyl
      fluorescence data is in agreement with those obtained from the kinetic analysis;
      therefore, the induced conformational changes were correlated to the
      isomerization of EI to EI*.

PMID- 16982156
TI  - Analysis of burns caused by pre-filled gas canisters used for lamps or portable
      camping stoves.
AB  - The use of pre-filled valveless gas canisters for lamps or camping stoves has
      caused a number of serious burn incidents. We performed a retrospective analysis
      of all of the patients who were victims of such incidents admitted to the
      Marseille Burn Centre between January 1990 and March 2004. There were a total of
      21 patients burned in such conditions. Adult males made up the majority of the
      victims of this sort. Lesions were often extensive (60% of the patients were
      burned over more than 10% of their body surface) and systematically deep. In
      order of frequency, burn locations were: the lower limbs, the upper limbs, the
      hands and the face. The incidents principally occurred during replacement of the
      canister near an open flame. The marketing of a canister with a valve in order to
      avoid gas leaks did not cause the old canisters to be taken off the market. On
      the contrary, European Safety Standard EN417, updated in October 2003, validated
      the use of these valveless canisters. The severity of the lesions caused and the
      existence of safe equivalent products requires the passage of a law that forbids
      valveless canisters.

PMID- 16982157
TI  - Stress hormones and emotion-regulation in two genetic animal models of
      depression.
AB  - Children of depressed parents often exhibit emotion-regulation deficits,
      characterized by either excessive withdrawal or approach strategies toward the
      mother. The current study examined behavioral and physiological emotion
      regulation in preweanling pups (postnatal day 17-19) belonging to two different
      genetic animal models of depression, Wistar-Kyoto (WKY) and Flinders Sensitive
      Line (FSL) rats. The study also examined the effects of stress on the two animal
      models, hypothesizing an interactive effect of hereditary vulnerability and
      exposure to stress. Chronic-stress was simulated by providing limited bedding to
      the dam and litter for a week, in the early postnatal period. Acute-stress was
      generated by exposure to an adult male rat, an ethologically valid stressor.
      Emotion-regulation of the pups was examined using a Y-maze preference test and
      radioimmunoassay of Hypothalamic-Pituitary-Adrenal (HPA) axis hormones
      (corticosterone & adreno-corticotropin/ACTH). WKY and FSL pups exhibited reduced
      approach-behavior toward the dam, an emotion-regulation profile reminiscent of
      avoidant attachment evident in many children of depressed parents. In contrast,
      the two animal models did not show similar HPA axis activity. FSL pups exhibited
      markedly lower ACTH levels compared to controls, while WKY pups did not differ
      from controls. With regard to the stress manipulations, the limited-bedding
      condition had no effect, while the acute-stressor induced overall effects on all
      groups, with more pronounced reactivity evident in the WKY and FSL pups. Taken
      together, the experiments indicate a similar behavioral profile of the two
      strains at the preweanling period, while suggesting HPA dysfunction in only one
      of the strains.

PMID- 16982158
TI  - Economic manifestations of opiate addiction: evidence from historical data from
      colonial Indonesia.
AB  - The aim of this paper is to demonstrate, using an example, the utility of
      historical data to illuminate important questions in the field of drug dependence
      research. The literature on the consumption of addictive substances often
      characterizes users as being one of two types: "addicts" and "casual users." An
      econometric characterization of the responses of opium consumers in the late
      colonial Netherlands Indies to changes in the price of opium and other important
      variables is provided, which explicitly acknowledges the existence of different
      types of opium smokers, as modeled in the underlying theory. The results reveal
      systematic differences between the behavior of groups of high-intensity consumers
      and groups of low-intensity consumers. While the findings show that both groups
      showed similar total price elasticities, the high-intensity consumers were
      affected predominantly via changes in the number of users rather than in per
      capita consumption. In the course of the analysis, various analytic methods that
      are new to the field of drug dependence research are introduced.

PMID- 16982159
TI  - Molecular characterization of bovine rotavirus circulating in beef and dairy
      herds in Argentina during a 10-year period (1994-2003).
AB  - Group A bovine rotavirus (BRV) is one of the main causes of neonatal calf
      diarrhea. The present study reports the incidence of rotavirus diarrhea and the
      genotypes of BRV strains circulating in beef and dairy herds from Argentina,
      during a 10-year period (1994-2003). Group A BRV was detected in 62.5% (250/400)
      of the total studied cases of diarrhea. Positive cases were analyzed by
      heminested multiplex RT-PCR for P and G genotypes identification. Sixty percent
      of them were typed as P[5]G6, 4.4% P[11]G10, 4.4% P[11]G6 and 2.4% P[5]G10.
      Additionally, 9.2% of the cases were initially typed as G8 combined with P[5] or
      P[11], but sequence analysis revealed they belonged to genotype G6, lineage Hun4
      like. Partial typing was assessed in 12.0% of the cases. One of the partially
      typed samples was closely related to genotype G15. BRV was detected in 71% and
      58% of the outbreaks registered in beef and dairy farms, respectively. A clear
      differential distribution of G/P types was found according to the herd type.
      P[5]G6 was the prevalent strain in beef herds, while P[11] was the prevalent P
      type in dairy herds (71%), associated in similar proportions with G6 and G10,
      These findings indicate that BRV genotypes included in the current commercially
      available rotavirus vaccines (G6, G10, P[5] and P[11]) should protect calves from
      most Argentinean field strains. Nevertheless, continuous surveillance is
      necessary to detect the emergence of new variants.

PMID- 16982160
TI  - Protection in alpacas against Corynebacterium pseudotuberculosis using different
      bacterial components.
AB  - Corynebacterium pseudotuberculosis is a Gram positive bacterium that produces
      caseous lymphadenitis in sheep and goats, and a granulomatous lymphadenitis in
      llamas and alpacas. To evaluate the immune potential of different doses of cell
      wall and toxin components of C. pseudotuberculosis from alpaca origin, 12 adult
      alpacas were allotted at random to four groups, and SC inoculated in the left
      flank with vaccines composed of low and high doses of bacterial crude antigens,
      cell wall: 250 and 500 microg/ml and toxin: 133 and 265 microg/ml, respectively.
      The vaccines were supplemented with 20 microg/ml of muramyl dipeptide as
      adjuvant. Three alpacas were sham inoculated with adjuvant as a control. After 3
      weeks, immunized and naive alpacas were challenged intradermally in the right
      flank with 1 x 10(6) colony forming units (CFU) of C. pseudotuberculosis. The
      alpacas were sacrificed at days 28, 58 and 112 after inoculation, and the degree
      of protection induced by vaccines was demonstrated by the absence of abscesses
      and/or bacteria. The alpacas vaccinated with high dose of toxin, did not show
      abscesses. In contrast, the alpacas vaccinated with a low dose of toxin showed
      abscesses at the inoculation site, regional, and renal lymph nodes. The cell wall
      vaccinated alpacas showed a lesser degree of protection than the other groups
      with superficial and internal abscesses. The control alpacas had persistent fever
      and abscesses at the inoculation site, regional, and internal lymph nodes. In
      addition, a robust and early humoral response was observed in all vaccinated
      alpacas after challenge, lasting at least 3 months. The results suggest that the
      toxin of C. pseudotuberculosis is a very important antigen, inducing a dose
      dependant protective immunity against this bacterium in alpacas.

PMID- 16982161
TI  - Stability of canine distemper virus (CDV) after 20 passages in Vero-DST cells
      expressing the receptor protein for CDV.
AB  - Isolates 007Lm, S124C and Ac96I and a Vero cell-adapted Onderstepoort strain of
      canine distemper viruses (CDV) were examined for stability after passages in Vero
      cells expressing the canine signaling lymphocyte activation molecule (dogSLAM,
      the intrinsic receptor to CDV). These viruses passage once in Vero cells
      expressing dogSLAM (Vero-DST) cells (original) and after 20 passages (20p) were
      compared by using sequence analyses and growth characteristics. All four strains
      of 20p grew well and were slightly better than their originals. The 20p viruses
      developed a cytopathic effect slightly lower than the original strains. A few
      changes in amino acids in the H gene were between the 20p and the original
      viruses, but the sites of changes were not specific. Fragments of P, M and L
      genes of all strains showed no nucleotide changes after the passages. These
      results showed that: (1) passages of CDVs in Vero-DST cells induced amino acid
      changes only in the H gene, not in the P, M and L genes, unlike in a previous
      study with Vero cells; (2) passages did not markedly affect the growth
      characteristics of every viral strain. These results indicate that Vero cells
      expressing canine SLAM allow the isolation and passaging of CDV without major
      changes in viral genes.

PMID- 16982162
TI  - Cardiovascular impact of dobutamine in neonates with myocardial dysfunction.
AB  - OBJECTIVE: To study effects of dobutamine on cardiac functional parameters,
      cerebral, mesenteric and renal blood flow in preterm neonates with myocardial
      dysfunction. STUDY DESIGN: Prospective evaluation of Doppler sonographically
      measured left ventricular systolic time intervals, stroke volume (SV), cardiac
      output (CO), and blood flow parameters of anterior cerebral artery (ACA),
      superior mesenteric artery (SMA) and renal arteries (RA), before, after 20 min
      and 8-10 h of dobutamine treatment in 20 neonates (gestational age 29.6+/-4.4
      weeks, birth weight 1450+/-609 g and postnatal age 2+/-2.1 days). Dobutamine was
      given in a mean dosage of 9.1+/-1.1 microg/kg. RESULTS: After 20 min SV increased
      from 1.71+/-0.5 ml to 2.12+0.57 ml/kg, CO from 223+/-76 to 290 ml/kg/min. A
      shortening of left ventricular pre ejection period from 86+/-12 to 66+/-13 ms and
      of the ratio of pre-ejection period/ejection time from 0.52+/-0.12 to 0.40+/-0.11
      were observed. Blood flow velocities of ACA increased after 8-10 h: peak systolic
      flow velocity (PSV) from 19.0+/-6 to 29.6+/-7.1 ms, end diastolic velocity (EDV)
      from 2.9+/-2.6 to 12.7+/-11.3 ms. PSV of SMA increased from 32.5+/-4.7 to 49.7+/
      7.8 ms after 8-10 h, EDV from 8.9+/-8 ms to 20.6+/-6.1 ms. PSV of RA increased
      from 18.2+/-6.1 ms to 39.9+/-4.8 ms, EDV from 2.2+/-1.2 to 8.2+/-2.1 ms after 8
      10 h. The pulsatility indices decreased significantly after 8-10 h: ACA from
      2.3+/-0.6 to 1.4+/-0.5, SMA from 1.7 to 1.2 and RA from 2.57 to 1.57. CONCLUSION:
      Dobutamine improves the cardiac functional parameters already after 20 min and
      has an influence on the blood flow parameters of ACA, SMA and RA 8-10 h after
      administration in neonates with myocardial dysfunction.

PMID- 16982163
TI  - The effect of water solubility of solutes on their flux through human skin in
      vitro.
AB  - The Flynn database (n=97) for determining the effect of the physicochemical
      properties of solutes on their skin absorption has been edited to give a database
      for which the solubilities of the solutes in water, S(AQ), and their maximum
      fluxes from water through human skin in vitro, J(MAQ), are known or can be
      calculated (n=76). Data from the six major contributors to the original Flynn
      database have been included. Data for solutes, which were significantly ionized
      or for experiments using different thicknesses of skin were not excluded so that
      the edited database is as diverse as the original. The edited database was fit to
      five equations where the independent variables were solubility in octanol
      (S(OCT)) in water (S(AQ)) or molecular weight (MW), and combinations of those
      three variables; and the dependent variable was J(MAQ). The best fit was obtained
      from the Roberts-Sloan (RS) equation: logJ(MAQ)=x+ylogS(OCT)+(1-y)logS(AQ)-zMW,
      x=-3.00, y=0.73, z=0.0048, r(2)=0.934, S.D.=0.37 and F=274. This result is
      important because J (amount/area time) is the more clinically useful descriptor
      of permeation compared to P (distance/time); and because the identification of
      S(AQ) as a significant variable in predicting flux changes the design parameters
      for optimizing topical delivery of drugs from solubility in lipids (or partition
      coefficients between OCT and AQ, K(OCT:AQ)) and MW, to solubility in lipids,
      S(OCT), and in water, S(AQ), as well as MW.

PMID- 16982164
TI  - Response adaptation to broadband sounds in primary auditory cortex of the awake
      ferret.
AB  - Driven by previous reports of adaptation to persistent stimuli in other brain
      regions, we investigated adaptive effects in the Primary Auditory Cortex of awake
      non-behaving ferrets (Mustela putorius furo). Electrophysiological data was
      obtained in response to the presentation of auditory gratings with a structured
      spectro-temporal envelope of varying bandwidth which had repeated transitions
      between low and high modulation depths. The responses were analyzed in terms of
      the evoked spike rates and in terms of the degree of phase locking to the
      modulation. We found two populations of cells, both of which showed adaptation in
      the traditional sense. For one population, we also found a second order of
      adaptation--i.e., adaptation of the adaptation. This suggests the existence of at
      least two coding strategies which differ in the weight placed on sensory context.

PMID- 16982165
TI  - Hearing in large (Eidolon helvum) and small (Cynopterus brachyotis) non
      echolocating fruit bats.
AB  - Comparing the hearing abilities of echolocating and non-echolocating bats can
      provide insight into the effect of echolocation on more basic hearing abilities.
      Toward this end, we determined the audiograms of two species of non-echolocating
      bats, the straw-colored fruit bat (Eidolon helvum), a large (230-350 g) African
      fruit bat, and the dog-faced fruit bat (Cynopterus brachyotis), a small (30-45 g)
      bat native to India and Southeast Asia. A conditioned suppression/avoidance
      procedure with a fruit juice reward was used for testing. At 60 dB SPL, the
      hearing range of E. helvum extends from 1.38 to 41 kHz with best sensitivity at
      8k Hz; the hearing range of C. brachyotis extends from 2.63 to 70 kHz with best
      sensitivity at 10 kHz. As with all other bats tested so far, neither species was
      able to hear below 500 Hz, suggesting that they may not use a time code for
      perceiving pitch. Comparison of the high-frequency hearing abilities of
      echolocating and non-echolocating bats suggests that the use of laryngeal
      echolocation has resulted in additional selective pressure to hear high
      frequencies. However, the typical high-frequency sensitivity of small non
      echolocating mammals would have been sufficient to support initial echolocation
      in the early evolution of bats, a finding that supports the possibility of
      multiple origins of echolocation.

PMID- 16982166
TI  - Brazilian plants with possible action on the central nervous system: a study of
      historical sources from the 16th to 19th century.
AB  - Brazil is a country rich in biodiversity, endemism, and cultural diversity,
      inhabited by different types of population. European expeditions and the
      migratory processes that began in the 16th century greatly contributed both to
      cultural diversity and to Brazilian popular therapeutics, and produced the first
      records on medicinal plants in Brazil. This study comprises a bibliographical
      survey of historic books found in Sao Paulo libraries (16th through 19th
      centuries) on medicinal plants exerting effects on the central nervous system
      (CNS). Thirty-four plants native to Brazil were selected from the reading of the
      books. Of these 34 plants, 13 were also recorded in ethnopharmacological studies
      among modern Brazilian communities and 16 have been studied phytochemically. Only
      eight have been the object of pharmacological studies, six of these, recently,
      with a request for a patent. Results showed that most of the species recorded in
      this study have been reported as medicinal for centuries, but have never been the
      object of pharmacological investigation down to the present time. Such results
      provide ideas for a selection of these species as potentially bioactive to be
      included in future pharmacological studies.

PMID- 16982167
TI  - Mild oliguria in preterm infants who later developed periventricular
      leukomalacia.
AB  - The aim of this study is to determine whether or not renal involvement was
      present during the early neonatal period in preterm infants with PVL. We
      conducted a case-control study. The following items were evaluated; urine output,
      serum levels of sodium (Na), potassium (K), chloride (Cl), urea nitrogen (UN),
      and creatinine (Cr). The factors that could influence the urine output were also
      compared between the PVL and the control group. The mean urine output during the
      first 24h in the PVL group was 19.8ml/kg/day, and was significantly lower than in
      the control group (28.8ml/kg/day, p<0.05). The mean UN and Cr were not
      significantly different between the two groups. The minimal serum Na and Cl
      levels in the PVL group were significantly lower (128.3 and 94.3mEq/l) than those
      in the control group (134.8 and 100.7mEq/l, p<0.01 each). The maximal serum K
      level was significantly higher in the PVL group (6.47mEq/l) as compared to the
      control group (5.57mEq/l, p<0.05). There were no differences in any postnatal
      variables between the two groups. The preterm infants who later developed PVL had
      mild but significant oliguria during the first 24h of life. This suggests that
      preterm infants with PVL will have renal involvement immediately after birth.

PMID- 16982168
TI  - Investigating the decision-making needs of HIV-positive women in Africa using the
      Ottawa Decision-Support Framework: Knowledge gaps and opportunities for
      intervention.
AB  - OBJECTIVE: To examine HIV-positive women's decision making in the context of
      pregnancy and HIV/AIDS and to explore interventions that may enhance and develop
      women's decision-making capacity in the sub-Saharan African context. METHODS: The
      Ottawa Decision-Support Framework was used to assemble evidence of women's
      decision-making needs. Several electronic databases were searched and an Internet
      search of the World Wide Web was conducted to search grey literature sources. An
      evidence-based approach to assessing benefits, harms and current practices was
      employed. RESULTS: Several gaps in our knowledge about women's decision making in
      the context of pregnancy and HIV were identified. The availability of evidence
      varied for each decision; however, significant gaps included: evidence around
      testing for ones status, advanced directives for self and child, disclosure
      (specifically, the impact of), others perceptions of antiretroviral use and data
      on termination of pregnancies. CONCLUSION: Decision making as a concept was
      generally not addressed in the MTCT literature. Evidence regarding the
      perceptions of women and others regarding the various decisions was often not
      available and subsequently an important aspect of MTCT interventions neglected.
      PRACTICE IMPLICATIONS: Incorporating a multi-disciplinary decision-support
      framework may prove useful to promote women's autonomy and involvement in MTCT
      related decision making.

PMID- 16982169
TI  - Progression of atherosclerotic renovascular disease: A prospective population
      based study.
AB  - OBJECTIVE: Previous reports from select hypertensive patients suggest that
      atherosclerotic renovascular disease (RVD) is rapidly progressive and associated
      with a decline in kidney size and kidney function. This prospective, population
      based study estimates the incidence of new RVD and progression of established RVD
      among elderly, free-living participants in the Cardiovascular Health Study (CHS).
      METHOD: The CHS is a multicenter, longitudinal cohort study of cardiovascular
      risk factors, morbidity, and mortality among men and women aged >65 years old.
      From 1995 through 1996, 834 participants underwent renal duplex sonography (RDS)
      to define the presence or absence of significant RVD. Between 2002 and 2005, a
      second RDS study was performed in 119 participants (mean study interval, 8.0 +/-
      0.8 years). Significant RVD was defined as hemodynamically significant stenosis
      (renal artery peak systolic velocity [RA-PSV] exceeding 1.8 m/s) or renal artery
      occlusion. Prevalent RVD was significant RVD at the first RDS, and incident
      disease was defined as new significant RVD at the second RDS. Significant change
      of RVD was defined as a change in RA-PSV of greater than two times the standard
      deviation of expected change over time, regardless of hemodynamic significance or
      progression to renal artery occlusion. RESULTS: The second RDS study cohort
      included 119 CHS participants with 235 kidneys (35% men; mean age, 82.8 +/- 3.4).
      On follow-up, no prevalent RVD (n = 13 kidneys; 6.0%) progressed to occlusion.
      Twenty-nine kidneys without RVD at the first RDS demonstrated significant change
      in PSV at the second RDS; including nine kidneys with new significant RVD (8 new
      stenoses; 1 new occlusion). Controlling for within-subject correlation, the
      overall estimated change in RVD among all 235 kidneys was 14.0% (95% confidence
      interval [CI], 9.2% to 21.4%), with progression to significant RVD in 4.0% (95%
      CI, 1.9% to 8.2%). Longitudinal increase in diastolic blood pressure and decrease
      in renal length were significantly associated with progression to new (ie,
      incident) significant RVD but not prevalent RVD. CONCLUSIONS: This is the first
      prospective, population-based estimate of incident RVD and progression of
      prevalent RVD among free-living elderly Americans. In contrast to previous
      reports among select hypertensive patients, CHS participants with a low rate of
      clinical hypertension demonstrated a significant change of RVD in only 14.0% of
      kidneys on follow-up of 8 years (annualized rate, 1.3% per year). Progression to
      significant RVD was observed in only 4.0% (annualized rate, 0.5% per year), and
      no prevalent RVD progressed to occlusion.

PMID- 16982170
TI  - Adjuvant arteriovenous fistula as means of rescue for infrapopliteal venous
      bypass with poor runoff.
AB  - OBJECTIVE: The aim of this study was to assess the outcome of infrapopliteal
      bypass when an adjuvant arteriovenous (AV) fistula was reconstructed as means of
      rescue as a result of poor runoff. The design was a retrospective multicenter
      case-control study. METHODS: Seventy-seven infrapopliteal vein bypasses required
      an adjuvant AV fistula among 1813 patients operated on for critical leg ischemia
      in 3 vascular centers between 1996 and 2003. The mean age was 74 years (range, 39
      90 years). A total of 70% of the patients had diabetes, and 24% had undergone
      previous vascular surgery. In 25% of the bypasses, the distal anastomosis was in
      a crural artery, in 55% it was in the dorsal pedal artery, and in 20% it was in a
      plantar artery. An adjuvant AV fistula was reconstructed in all cases because of
      poor intraoperative arterial status, intraoperative angiography, or low
      intraoperative flow. A control group was retrieved that matched the study group
      according to the recipient artery and runoff score. RESULTS: The primary and
      secondary patency were 61% and 75%, respectively, at 1 year in the AV fistula
      group and 57% and 71% in the control group. The 3-year patency rates were 49% and
      62% for the AV fistula group and 46% and 71% for the control group, respectively.
      There was a 76% leg-salvage rate at 3 years in the study group, compared with 87%
      in the control group. There were no major complications related to the AV
      fistula. Intraoperative flow was increased from a median of 20 mL/min to 115
      mL/min by the AV fistula (P = .003). The graft flow was significantly higher in
      the AV fistula group than in the control group (P = .001). CONCLUSIONS: The
      adjuvant AV fistula increased graft flow significantly in a poor-outflow venous
      bypass. In this extreme patient group, acceptable patency and leg salvage was
      achieved without adverse effects. Despite this, the AV fistula did not improve
      the outcome.

PMID- 16982172
TI  - Improving the clinical utility of the SIRS cognitive items: preliminary
      reliability, validity, and normative data in pretrial and clinical samples.
AB  - The utility of the Structured Interview of Reported Symptoms [SIRS; Rogers, R.,
      Bagby, R. M., & Dickens, S. E. (1992). Structured Interview of Reported Symptoms
      professional manual. Odessa, FL: Psychological Assessment Resources], Improbable
      Failure Rate (IF) scale in pretrial (N=64) and clinical (N=153) samples was
      explored. Internal consistencies of the IF items were alpha=.81 and alpha=.92,
      respectively, with split-half reliabilities of .89 and .84, respectively. The IF
      scale loaded distinctly from the SIRS primary (psychosis) scales in principal
      components analysis, and the pattern of performances among clinical groups were
      as expected (e.g., normal controls outperformed patients with focal lesions and
      dementia, CHI patients outperformed dementia patients). Performance on the IF
      items was correlated with MMSE score (r=-.59, p<or=.001), age (r=.53, p<or=.001),
      and education (r=.31, p<or=.001), but not with Barona estimated FSIQ (r=-.14,
      p=.08). For normals and psychiatric patients there was a clear falling off of IF
      error scores after 1 error, and for CHI patients the fall off began after 2
      errors. Results lend credence to the SIRS IF scale as an acceptable screening
      measure for feigned cognitive abilities.

PMID- 16982173
TI  - The Driving Cognitions Questionnaire: development and preliminary psychometric
      properties.
AB  - Recent research has suggested that fear of driving is common in the general
      population. People may have various concerns when driving, and instruments for
      the assessment of these concerns are lacking. The present paper describes the
      development and preliminary evaluation of the Driving Cognitions Questionnaire
      (DCQ). The DCQ is a 20-item scale that measures three areas of driving-related
      concerns--panic-related, accident-related, and social concerns. In three separate
      samples from different countries (n=69, 100, and 78), the scale showed good
      internal consistency and substantial correlations with measures of the severity
      of driving fear. It discriminated well between people with and without driving
      phobia. It also showed convergent validity with other measures. The questionnaire
      shows promise for use in research and clinical practice.

PMID- 16982174
TI  - A rapid method for microarray cross platform comparisons using gene expression
      signatures.
AB  - Microarray technology has become highly valuable for identifying complex changes
      in global gene expression patterns. The inevitable use of a variety of different
      platforms has compounded the difficulty of effectively comparing data between
      projects, laboratories, and public access databases. The need for consistent,
      believable results across platforms is fundamental and methods for comparing
      results across platforms should be as straightforward as possible. We present the
      results of a study comparing three major, commercially available, microarray
      platforms (Affymetrix, Agilent, and Illumina). Concordance estimates between
      platforms was based on mapping of probes to Human Gene Organization (HUGO) gene
      names. Appropriate data normalization procedures were applied to each dataset
      followed by the generation of lists of regulated genes using a common
      significance threshold for all three platforms. As expected, concordance measured
      by directly comparing gene lists was relatively low (an average 22.8% for all
      platforms across all possible comparisons). However, when statistical tests (gene
      set enrichment analysis--GSEA, parametric analysis of gene enrichment--PAGE)
      which align gene lists with continuous measures of differential gene expression
      were applied to the cross platform datasets using significant gene lists to poll
      entire datasets, the relatedness of the results from all three platforms was
      specific, obvious, and profound.

PMID- 16982175
TI  - Correlations of functional capacity and neuropsychological performance in older
      patients with schizophrenia: evidence for specificity of relationships?
AB  - BACKGROUND: Neuropsychological (NP) performance is a consistent correlate of
      everyday functioning in schizophrenia, but it is unclear whether relationships
      between individual NP ability areas and domains of everyday functioning are
      general or specific. Assessments of real-world everyday functioning may be
      influenced by environmental and social factors (e.g., social security, disability
      status, opportunities and restrictions in living situations). This study examined
      the specificity of the relationships between different NP abilities and
      performance-based measures of social and living skills. METHODS: 181 ambulatory
      older (age>50) patients with schizophrenia were examined with NP tests measuring
      episodic and working memory, executive functioning, verbal fluency, and
      processing speed. All subjects performed tasks examining social (Social Skills
      Performance Assessment: SSPA) and everyday living (UCSD Performance Based Skills
      Assessment: UPSA) skills. RESULTS: Using canonical analysis, the NP variables
      were used to predict the functional capacity measures. The analysis found that
      37% of the variance in the functional capacity and NP measures was shared, X(2)
      (54)=106.29, p<.001. Two canonical roots described the cognitive variables and
      the roots were differentially associated with everyday living and social skills.
      The root loading on processing speed, episodic memory, and executive functions
      were associated with UPSA scores, while the root loading on working and episodic
      memory and verbal fluency were associated most strongly with social competence.
      IMPLICATIONS: Social and everyday living skills deficits in patients with
      schizophrenia may reflect generally independent domains of functional outcome,
      linked through cognitive performance. The data suggest that somewhat different
      cognitive processes are associated with these two domains of functional capacity,
      although there appears to be some overlap, which may be due to the nature of the
      NP tests employed.

PMID- 16982176
TI  - Genetic transformation of Echinacea purpurea with Agrobacterium rhizogenes and
      bioactive ingredient analysis in transformed cultures.
AB  - A method of the transformed hairy roots cultures of Echinacea purpurea was
      established by infecting different types of explants with three type strains of
      Agrobacterium rhizogenes (A4, R1601 and R1000) in this paper. We obtained that
      the transformed percentage of E. purpurea leaves with A4, R1601 and R1000 were
      80%, 60%, 40%, respectively and that of E. purpurea leafstalks were 10%, 30%,
      45%, respectively. The contents of polysaccharides and phenolic compounds were
      measured in transformed hairy roots and non-transformed roots after 2 months in
      culture. For transformed hairy roots, the contents of polysaccharides and
      phenolic compounds were 236.0 and 18.9 mg g(-1) DW, respectively. While the
      contents of polysaccharides and phenolic compounds in non-transformed roots were
      161.5 and 33.3 mg g(-1) DW, respectively.

PMID- 16982177
TI  - Solubilization and dissolution of insoluble weak acid, ketoprofen: effects of pH
      combined with surfactant.
AB  - This study investigated the combined effect of pH and surfactant on the
      solubility and dissolution of ketoprofen (KP), a highly permeable and an
      ionizable and water-poorly soluble drug in gastrointestinal tract. The
      equilibrium solubility of KP was determined in buffers at the pH range from 4.0
      to 6.8 and sodium lauryl sulfate (SLS) concentrations from 0% to 2.0%. Its
      intrinsic dissolution rate was measured in the same media using a rotating disk
      apparatus. A simple additive model accounting for the free unionized KP and
      ionized KP(-) forms, and their corresponding micellar forms was employed to study
      the in vitro solubility and dissolution behavior. Non-linear regression analysis
      showed that the proposed model agreed well with the experimental data, with
      R(sq)=0.96 (P<0.0001) for the solubility study, and R(sq)=0.98 (P<0.0001) for the
      intrinsic dissolution rate measurement. The pK(a) and c(KP) values are estimated
      as 4.76+/-0.00 and 0.253+/-0.05 mg/mL, respectively, in good agreement with
      literature reports. The micellar solubilization coefficient k(*) for the
      unionized [KP](micelle) is 757+/-165 L/mol, whereas the value k(**) for the
      ionized [KP(-)](micelle) is 9.88+/-6.70 L/mol. The diffusion coefficients of
      various species: KP, KP(-), [KP](micelle), and [KP(-)](micelle), are 7.68 x 10(
      6), 1.54 x 10(-6), 2.32 x 10(-7), and 2.13 x 10(-20)cm(2)/s, respectively. The
      maximum enhancement of solubilization is approximately 232-fold, while the
      maximum dissolution amplification is only 54-fold because of the smaller
      diffusivity of micellar species. The dramatic enhancement of in vitro
      solubility/dissolution attributable to an increase of pH and presence of SLS
      mimics the in vivo solubilization/dissolution behavior of KP along the
      gastrointestinal tract, when the pH increases from 1-2 in the stomach to 5-6 in
      the duodenum. The results suggest that the KP dissolves very rapidly in small
      intestine, implying that its absorption will be predominantly controlled by
      gastric emptying, and only minimally limited by the subsequent dissolution
      processes. This behavior is very similar to BCS I drugs, thus KP may be
      considered for possible waivers of bioequivalence.

PMID- 16982179
TI  - Toxicity of an effective amphotericin B formulation at high cationic lipid to
      drug molar ratio.
AB  - Therapeutic activity of an effective and less nephrotoxic amphotericin B (AMB)
      formulation with dioctadecyldimethylammonium bromide (DODAB) bilayer fragments
      (named DODAB/AMB) inspired this toxicity survey in mice. At low drug to lipid
      molar ratios, hepatotoxicity, spleen damage and blood changes in comparison to
      DOC/AMB (sodium desoxycholate/amphotericin B, Fungizone) are evaluated ultimately
      showing toxic effects associated to DODAB only. Swiss Webster female mice were
      given DODAB, DODAB/AMB or DOC/AMB intraperitonially (ip) for 10 consecutive days
      (0.4 mg/kg/day AMB; 80 mg/kg/day DODAB) and repeated dose-toxicity was evaluated
      at the end of the treatment period (on day 11) and after a recovery period of 6
      months from biochemical and hematological parameters plus histopathological
      examination of spleen and liver. Both at day 11 and 180, DODAB in the formulation
      administered ip causes irreversible changes in spleen such as fibrosis and
      leukocytes infiltration as a consequence of the administration route. Whereas
      focal necrosis is induced by DODAB in liver at day 180, DOC/AMB causes more
      severe multifocal necrosis both at day 11 and day 180. In the kidneys, the novel
      formulation preserves integrity of tubules and glomeruli in contrast to the
      serious damage caused by DOC/AMB as shown previously. The majority of the toxic
      effects observed for the novel formulation were due to the DODAB carrier used at
      10mg/mL, i.e., at a rather high concentration and further studies should minimize
      DODAB dose.

PMID- 16982178
TI  - Reversed chitosan-alginate polyelectrolyte complex for stability improvement of
      alpha-amylase: optimization and physicochemical characterization.
AB  - The present work explores, using response surface methodology, the main and
      interaction effects of some process variables on the preparation of a reversed
      chitosan-alginate polyelectrolyte complex (PEC) with entrapped alpha-amylase for
      stability improvement. A 3(3) full factorial design was used to investigate the
      effect of the chitosan and alginate concentrations and hardening time on the
      percent entrapment, time required for 50% (T(50)) and 90% (T(90)) enzyme release,
      and particle size. The beads were prepared by dropping chitosan containing alpha
      amylase into a sodium alginate solution without any salt. The in vitro enzyme
      release profile of the beads was fitted to various release kinetics models to
      study the release mechanism. A topographical characterization was carried out
      using scanning electron microscopy (SEM), and the entrapment was confirmed using
      Fourier transform infrared (FTIR) spectroscopy and differential scanning
      calorimetry (DSC). Stability testing was carried out according to the
      International Conference on Harmonization (ICH) guidelines for zones III and IV.
      Beads prepared using 2.5%w/v chitosan and 3%w/v sodium alginate with a hardening
      time of 60 min had more than 90% entrapment and a T(90) value greater than 48
      min. Moreover, the shelf-life of the enzyme-loaded beads was found to increase to
      3.68 years, compared with 0.99 years for the conventional formulation. It can be
      inferred that the proposed methodology can be used to prepare a reversed PEC of
      chitosan and alginate with good mechanical strength, provided both the reactants
      are in a completely ionized form at the time of the reaction. Proper selection of
      the reaction pH, polymer concentration and hence charge density, and hardening
      time is important and determines the characteristics of the PEC.

PMID- 16982180
TI  - Sequences and domain structures of mammalian, avian, amphibian and teleost
      tropoelastins: Clues to the evolutionary history of elastins.
AB  - Tropoelastin is the monomeric form of elastin, a polymeric extracellular matrix
      protein responsible for properties of extensibility and elastic recoil in
      connective tissues of most vertebrates. As an approach to investigate how
      sequence and structural characteristics of tropoelastin assist in polymeric
      assembly and account for the elastomeric properties of this polymer, and to
      better understand the evolutionary history of elastin, we have identified and
      characterized tropoelastins from frog (Xenopus tropicalis) and zebrafish (Danio
      rerio), comparing these to their mammalian and avian counterparts. Unlike other
      species, two tropoelastin genes were expressed in zebrafish. All tropoelastins
      shared a predominant and characteristic alternating domain arrangement, as well
      as the fundamental crosslinking sequence motifs. However, zebrafish and frog
      tropoelastins had several unusual characteristics, including increased exon
      numbers and protein molecular weights, and decreased hydropathies. For all
      tropoelastins there was evidence of evolutionary expansion of the proteins by
      extensive replication of a hydrophobic-crosslinking exon pair. This was
      particularly apparent for zebrafish and frog tropoelastin genes, where remnants
      of sequence similarity were also seen in introns flanking the replicated exon
      pair. While overall alignment of mammalian, avian, frog and zebrafish
      tropoelastin sequences was not possible because of sequence variability, the C
      terminal exon was well-conserved in all species. In addition, good sequence
      alignment was possible for several exons just upstream of the putative region of
      replication, suggesting that these conserved domains may represent 'primordial'
      core sequences present in the ancestral sequence common to all tropoelastins and
      in some way essential to the structure/function of elastin.

PMID- 16982181
TI  - Increased in CD8 T lymphocytes in the BAL fluid of patients with sulfur mustard
      gas-induced pulmonary fibrosis.
AB  - OBJECTIVE: In an attempt to understand better the potential role of the T cell in
      the pathogenesis of pulmonary fibrosis (PF) due to sulfur mustard gas inhalation,
      this study was designed to analyze bronchoalveolar lavage (BAL) lymphocyte
      subsets and to determine the ratio of CD4 to CD8 lymphocytes in BAL fluid.
      SETTING: University hospital. PATIENTS: Twenty-one veterans with mustard gas
      induced pulmonary fibrosis and 20 normal veterans as control group. INTERVENTION:
      Chest roentgenograms, pulmonary function tests (PFTs), tests for carbon monoxide
      diffusing capacity of the lung (DLCO), high-resolution CT scans of the chest, BAL
      via fiberoptic bronchoscopy, analyses of BAL fluids for cellular and Flow
      cytometric analysis of the phenotype of bronchoalveolar cells were performed in
      all cases. A transbronchial lung biopsy was done in all patients following BAL.
      RESULTS: Neutrophilic alveolitis was the predominant feature. Neutrophils
      (P<0.0001) and eosinophils (P=0.0006) were the predominant cell types in the BAL
      fluid of patients with PF. CD8 lymphocytes expressed as percentage or absolute
      number were significantly higher in patients with PF than in healthy controls
      (22.96+/-7.48% vs. 14.16+/-7.73%, respectively; P=0.0006; and 2.28+/-0.84 vs.
      1.10+/-0.55 x 10(3) cells/ml, respectively; P<0.0001). The CD4/CD8 ratio was
      significantly lower in patients with PF than in healthy controls (0.73+/-0.25 vs.
      1.58+/-0.67; P<0.0001). Except for the percentage and the absolute number of the
      BAL fluid neutrophils (r=0.70, P=0.001: r=-0.62, P=0.005; respectively), no
      correlation was found between DLCO% and the other BAL cells. A significant
      negative correlation was observed between the percentage of DLCO and both the
      percentage and the absolute number of CD8 lymphocytes in BAL fluid in patients
      with PF (r=-0.81, P=0.0003; r=-0.61, P=0.006; respectively). A significant
      correlation was also seen between the percentage of DLCO and the CD4/CD8 ratio
      (r=-0.60, P=0.006) in our patients. CONCLUSION: CD8 T cells in BAL fluid were
      significantly elevated in patients with pulmonary fibrosis. Patients with higher
      grades of pulmonary fibrosis expressed as percentage of DLCO, revealed higher
      percentages and the absolute number of CD8 T cells and a lower CD4/CD8 ratio.

PMID- 16982182
TI  - A novel potent inhibitor of inducible nitric oxide synthase, ONO-1714, reduces
      hyperoxic lung injury in mice.
AB  - STUDY OBJECTIVES: High-concentration oxygen therapy is used to treat tissue
      hypoxia, but hyperoxia causes lung injury. Overproduction of nitric oxide by
      nitric oxide synthase (NOS) is thought to promote hyperoxic lung injury. The
      present study was conducted to examine the role of inducible nitric oxide
      synthase (iNOS) in hyperoxic lung injury in mice. MEASUREMENTS AND RESULTS: Mice
      were exposed to >98% oxygen for 72 h, and ONO-1714 (0.05 mg/kg) (ONO) was
      subcutaneously administered to block iNOS. Hyperoxia significantly increased
      total cell count, protein concentration, and nitrites/nitrates in the
      bronchoalveolar lavage fluid and proinflammatory cytokines in the lung tissue.
      ONO significantly prevented the increases in all of these variables. ONO
      suppressed histologic evidence of lung injury. ONO markedly inhibited iNOS
      protein expression and nitrotyrosine production in lung homogenates. After
      exposure to hyperoxia, alveolar epithelial cells stained positively for 8-hydroxy
      2'-deoxyguanosine, a proper marker of oxidative DNA damage by reactive oxygen
      species. ONO attenuated this finding. CONCLUSIONS: NOS play important roles in
      the pathogenesis of hyperoxic lung injury. Selective iNOS inhibitors may be
      useful for the treatment of hyperoxic lung injury.

PMID- 16982183
TI  - Antifungal treatment in sarcoidosis--a pilot intervention trial.
AB  - BACKGROUND: Sarcoidosis is generally treated with corticosteroids that are not
      always an effective therapy. OBJECTIVES: To assess if treatment with antifungal
      drugs would improve the clinical status of patients with sarcoidosis. METHODS:
      Patients (n=18) with sarcoidosis grades II and III according to established
      criteria and without clinical and immunological signs of fungal infection, were
      treated with antifungal medication together with corticosteroids for 3-6 months.
      Pulmonary X-ray infiltration, lung function, and severity of symptoms were
      registered before and after the treatment and at follow up 9-58 months later.
      RESULTS: The treatment resulted in statistically significant decreases in the
      degree of pulmonary infiltration with an average decrease in the group from 2.0
      to 1.0. There were also significant increases in diffusion capacity and decreases
      in the severity of symptoms. CONCLUSION: It is suggested that treatment with
      antifungal drugs may be useful, at least in certain cases of sarcoidosis.

PMID- 16982184
TI  - Nanocrystalline silicon-based oligonucleotide chips.
AB  - A novel oligonucleotide array sensor has been developed with nanocrystalline Si
      (ncSi) substrates. The ncSi was prepared by electrochemical etching technique.
      Our study indicated that both the binding capacity and the hybridization
      efficiency are dependent upon the particle size of ncSi. In contrary, the chips
      developed with Si substrates exhibit the lower binding capacity and hybridization
      efficiency. The improved performances of the sensor chips are attributed to the
      large specific surface area of ncSi compared to the existing conventional
      techniques. The sensor chips with the ncSi substrate of 13 nm-sized particle can
      be regenerated and reused for at least 12 times. The oligonucleotide array sensor
      also shows high stability, which can bear relatively the stringent conditions
      (e.g. 80 degrees C, 75% of relative humidity and 3.6 klx of irradiation).

PMID- 16982185
TI  - Simultaneous determination of ascorbic acid and dopamine in the presence of uric
      acid on ruthenium oxide modified electrode.
AB  - RuOx x nH2O film was electrochemically synthesized conveniently using cyclic
      voltammetric technique. The film formation was ascertained by the Electrochemical
      quartz crystal microbalance (EQCM) method and 45 ng of deposit per cycle was
      obtained. Stoichiometric ratio of the ruthenium and ruthenium oxide have been
      studied with different pH of phosphate buffer. The stability of the modified
      electrode in the presence of different cations and anions with different
      concentrations and pH were examined. Electrochemical studies have shown that the
      ascorbic acid (AA) and dopamine (DA) catalytic oxidation on ruthenium oxide
      modified electrode (RME) with a span of 300 mV separation even in the presence of
      uric acid (UA) with a large decrease in their respective over potential compared
      with bare glassy carbon electrode (GC). Accidentally, the reversible redox
      properties of the AA have been expediently studied on the RME using cyclic
      voltammetry and this peculiarity was interrogated through rotating ring disc
      electrode (RRDE) experiments. RRDE experiment results are conformed to the CV
      studies result and thus reversible redox property of AA have been reiterated.
      Amperometric detection under stirred condition up to approximately 0.8mM of AA
      and DA was carried out at free of electrode fouling. Interestingly, the
      regeneration of used RME electrode even after many consequent analysis, 100% was
      obtained.

PMID- 16982186
TI  - Do we live in a quantum world? Advances in multidimensional coherent
      spectroscopies refine our understanding of quantum coherences and structural
      dynamics of biological systems.
AB  - The issue of quantum effects in biological functions reduces to determining the
      relevant length and/or time scales over which phase relationships (coherence) in
      the wave properties of matter are conserved and lead to observable interference
      effects. Recent advances in femtosecond laser-based two-dimensional spectroscopy
      and coherent control have made it possible to directly determine the relevant
      timescales of quantum coherence in biological systems and even manipulate such
      effects, respectively, and also provide direct information on the interactions
      between the different degrees of freedom (electronic and nuclear) with sufficient
      time resolution to catch the very chemical processes driving biological functions
      in action. The picture that is emerging is that there are primary events in
      biological processes that occur on timescales commensurate with quantum coherence
      effects.

PMID- 16982187
TI  - Induction of A.T to G.C mutations by erroneous repair of depurinated DNA
      following estrogen treatment of the mammary gland of ACI rats.
AB  - Evidence suggests that the genotoxic mechanism of estrogens (estrone/estradiol)
      in breast cancer involves their oxidation to 3,4-quinones and reaction with DNA
      to form depurinating N3Ade and N7Gua adducts. We examined whether estrogen
      genotoxicity is mutagenic in the mammary gland of the female ACI rat, a model for
      estrogen-dependent breast cancer. Mutagenesis was studied by PCR amplification of
      the H-ras1 gene (exons 1-2), cloning in pUC18, transforming Escherichia coli, and
      sequencing the inserts in plasmids from individual colonies. Mammary glands of
      both estrogen-responsive (ACI and DA) and resistant (Sprague-Dawley) rats
      contained pre-existing mutations at frequencies of (39.8-58.8)x10(-5), the
      majority (62.5-100%) of which were A.T to G.C transitions. Estradiol-3,4-quinone
      (200 nmol) treatment of ACI rats caused rapid (6h to 1 day) mutagenesis
      (frequency (83.3-156.1)x10(-5); A.T to G.C 70-73.3%). The estrogen-induced A.T to
      G.C mutations were detected as G.T heteroduplexes, as would be expected if N3Ade
      depurinations caused Gua misincorporations by erroneous repair. These
      heteroduplexes were identified by the T.G-DNA glycosylase (TDG) assay. TDG
      converts G.T heteroduplexes to G.abasic sites, rendering DNA templates refractory
      to PCR amplification. Consequently, A.T to G.C mutations present as G.T
      heteroduplexes in the DNA are eliminated from the spectra. TDG treatment of
      mammary DNA from estradiol-3,4-quinone-treated ACI rats brought A.T to G.C
      mutations down to pre-existing frequencies. Our results demonstrate that
      treatment with estradiol-3,4-quinone, an important metabolite of estrogens,
      produced A.T to G.C mutations in the DNA of the mammary gland of ACI rats.

PMID- 16982188
TI  - Comparative protein modeling and surface analysis of Leishmania sirtuin: A
      potential target for antileishmanial drug discovery.
AB  - Homology model of Leishmania SIR2 shed new light on the ligand binding features
      of this enzyme. The molecular electrostatic potentials (MESP), the cavity depth
      analysis, and LmSIR2-hSIRT2 models' superposition suggested that the nicotinamide
      binding catalytic domain has several minor but potentially important structural
      differences. These differences could be exploited for designing antileishmanial
      compounds.

PMID- 16982189
TI  - Positively coded photoaffinity label for altering isoelectric points of proteins.
AB  - Novel diazirinyl photoaffinity ligand, which contains (3-trifluoromethyl)
      phenyldiazirine and penta(epsilon-Boc-Lys) as a photoreactive code, allows the
      introduction of a positive cascade to alter the pI value of labeled components,
      facilitating the isolation of photolabeled biocomponents with isoelectric
      focusing techniques.

PMID- 16982191
TI  - Design, synthesis and in vivo activity of 9-(S)-dihydroerythromycin derivatives
      as potent anti-inflammatory agents.
AB  - The synthesis of a new class of 9-(S)-dihydroerythromycin derivatives and their
      anti-inflammatory activity on in vivo PMA assay are described. Modifying the
      desosamine sugar on the C-3' amino group, it was possible to differentiate
      between anti-biotic and anti-inflammatory action. The compounds are completely
      devoid of anti-microbial effects but their anti-inflammatory properties are
      enhanced. These results strongly suggest the potential of macrolides as a new
      class of anti-inflammatory agents.

PMID- 16982190
TI  - Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones
      with acyclic alanyl amides as P4 motifs.
AB  - Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2
      ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating
      an alanylamide P4 group with acyclic tertiary amide termini. Optimized
      hydrophobic contacts of one amide substituent in P4 were complemented by
      hydrophobicity-modulating features in the second, producing potent fXa inhibitors
      including examples with excellent anticoagulant properties.

PMID- 16982192
TI  - Arylsulfonamides: a study of the relationship between activity and conformational
      preferences for a series of factor Xa inhibitors.
AB  - Torsional scans of sulfonamide S-C bonds in small model systems of a series of
      arylsulfonamide factor Xa inhibitors were performed in order to investigate if
      conformational effects can help to rationalise the observed SAR. Computational
      results were in good agreement with the experimental data indicating that the
      sulfonamide conformation plays an important role in determining the activity in
      this particular series of factor Xa inhibitors.

PMID- 16982193
TI  - Discovery of small molecule inhibitors of integrin alphavbeta3 through structure
      based virtual screening.
AB  - Inhibitors of integrin alphavbeta3 have been implicated in the treatment of a
      variety of diseases, including tumor metastasis, neovascularization,
      osteoporosis, and rheumatoid arthritis. It is therefore desirable to develop new
      types of small molecule inhibitors of integrin alphavbeta3. Here we describe the
      discovery of novel classes of small molecule inhibitors, via structure-based
      virtual screening, that target the ligand binding site of integrin alphavbeta3.
      Application of the docking procedure for screening of a commercially available
      compound database resulted in a 1774-fold reduction in the size of the screening
      set (88695 to 50 compounds) and gave a hit-rate of 14% upon biological evaluation
      (IC50 value ranging from 30 to 200 microM). The best hit, compound 37, 3,4
      dichloro-phenylbiguanide, showed inhibitory activity, in a time- and dose
      dependent manner, in both cell motility and angiogenesis assays. Based on the
      best hit, compound 37, a more effective derivative compound 62 has been
      identified. Furthermore, molecular graphics analyses of a series of substituted
      phenylbiguanides were carried out to predict the binding mode between the active
      compounds and integrin alphavbeta3. Our results indicate that the substituted
      phenylbiguanides might be involved in the inhibition of bivalent cation-mediated
      ligand binding of integrin alphavbeta3.

PMID- 16982194
TI  - Breast core biopsy reporting categories--An internal validation in a series of
      3054 consecutive lesions.
AB  - We reviewed 3226 consecutive core biopsies (CBs) of 3054 mammographically
      detected breast lesions performed at our Centre from November 1993 to June 2003.
      CB diagnoses, classified according to the Non-operative Diagnosis Subgroup of the
      British National Health Service Breast Cancer Screening Programme (NHSBSP), were
      B5 (37.1%), B4 (0.5%), B3 (7.6%), B2 (50.9%) and B1 (3.9%). It was necessary to
      repeat the procedure in 172 cases (5.3%). The values for absolute sensitivity and
      specificity are 90.8% and 83.8%, respectively. The positive predictive value for
      categories B4 and B5 is 100%, with no false-positives. The positive predictive
      value for category B3 is 16.3%. The negative predictive value for B2 category is
      97.2%, with a false-negative rate of 3.5%. In conclusion, this system of analysis
      has enabled us to confirm that our CB results surpass the minimum recommended
      standards proposed by the NHSBSP.

PMID- 16982195
TI  - Walking speed influences on gait cycle variability.
AB  - The purpose of this study was to investigate the influence of walking speed on
      the amount and structure of the stride-to-stride fluctuations of the gait cycle.
      Based on previous findings for both walking [Hausdorff JM, Purdon PL, Peng CK,
      Ladin Z, Wei JY, Goldberger AL. Fractal dynamics of human gait: stability of long
      range correlations in stride interval fluctuations. J Appl Physiol 1996;80:1448
      57], and running [Jordan K, Challis JH, Newell KM. Long range correlations in the
      stride interval of running. Gait Posture 2006;24:120-5] it was hypothesized that
      the fractal nature of human locomotion is a reflection of the attractor dynamics
      of human locomotion. Female participants walked for 12min trials at 80%, 90%,
      100%, 110% and 120% of their preferred walking speed. Eight gait cycle variables
      were investigated: stride interval and length, step interval and length, and from
      the vertical ground reaction force profile the impulse, first and second peak
      forces, and the trough force. Detrended fluctuation analysis (DFA) revealed the
      presence of long range correlations in all gait cycle variables investigated.
      Speed related U-shaped functions occurred in five of the eight variables, with
      the minima of these curves falling between 100% and 110% of the preferred walking
      speed. These findings are consistent with those previously shown in running
      studies and support the hypothesis that reduced strength of long range
      correlations at preferred locomotion speeds is reflective of enhanced stability
      and adaptability at these speeds.

PMID- 16982196
TI  - Structure of the Ctr1 copper trans'PORE'ter reveals novel architecture.
AB  - Copper is essential for biological processes such as free radical detoxification,
      mitochondrial respiration and iron metabolism. A central player in copper
      homeostasis is the high-affinity integral plasma membrane copper transporter
      Ctr1. However, the precise mechanisms by which Ctr1 functions are not known.
      Here, we highlight an important breakthrough in our understanding of how Ctr1
      facilitates Cu(I) movement across membranes: the publication of structural
      details for human Ctr1 obtained from 2D crystallography and electron microscopy.

PMID- 16982197
TI  - Difficulties and limitations in minimally invasive repair of pectus excavatum--6
      years experiences with Nuss technique.
AB  - OBJECTIVE: In 1998, Dr Donald Nuss proposed minimally invasive repair of pectus
      excavatum (MIRPE) which did not require the osteochondrous parts of the anterior
      chest wall to be resected. The paper aims at presenting the authors' own 6 years
      of experience in funnel chest repair with MIRPE technique. Also, many technical
      problems of this method are discussed. MATERIALS AND METHODS: Between 1999 and
      2005, 461 patients (99 female and 362 male, aged 3-31 years, mean age 15.2 years)
      with pectus excavatum were operated with the Nuss technique. All patients were
      operated-on according to the original operative protocol proposed by Donald Nuss.
      With growing experience, own modifications were introduced. Insertion of two bars
      was done in 17.4%, transverse sternotomy in adolescents with rigid anterior chest
      wall in 7.8%, limited excision of the rib cartilages in 5.9%, and parasternal
      fixation of the bar to prevent it from rotating in 59.7% of patients. RESULTS:
      There were no deaths. Intraoperative complications were noted in 19 (4.1%)
      patients and postoperative ones were observed in 43 (9.3%) patients. The
      operative time ranged from 25 to 130 min (52 min on average). In 192 (41.6%)
      patients, an epidural block was used. The hospital stay ranged from 4 to 12 days
      with the mean of 5.3 days. A redo procedure for the bar rotation was necessary in
      13 (2.8%) patients. The support bar has been removed in 260 (56.4%) patients so
      far. In all the patients, an adequate contour of the anterior chest wall has been
      maintained. CONCLUSIONS: MIRPE proposed by Nuss has all the features of a
      minimally invasive procedure and is straightforward. Better clinical results are
      achievable in patients under 12 years of age with a symmetric deformity. In older
      patients (over 15 years of age) with a rigid chest or with an asymmetric
      deformity, additional procedures are required to achieve a comprehensive
      correction of the deformity. Recent results and forward clinical observations may
      give proof to establish MIRPE as a method of choice in funnel chest correction.

PMID- 16982198
TI  - Vesicle disruption, plasma membrane bleb formation, and acute cell death caused
      by illumination with blue light in acridine orange-loaded malignant melanoma
      cells.
AB  - Acridine orange (AO), a weakly basic fluorescent dye, is permeable to plasma and
      vesicle membranes and preferentially remains in intracellular acidic regions.
      Using fluorescence microscopy, we observed dynamic changes in AO-loaded cultured
      malignant melanoma cells during illumination with blue light. Immediately after
      the start of the illumination, the successive disruption of vesicles was observed
      as a flash of fluorescence, and shortly after that, blebs were formed on the
      plasma membrane. These cells died within 5 min. Vesicle disruption was completely
      inhibited when cells were treated with the vacuolar H(+)-ATPase inhibitor
      bafilomycin A1 followed by loading with AO, but not when bafilomycin A1 was
      treated after AO loading. Thus, the filling of AO in the vesicle, which is driven
      by vacuolar H(+)-ATPase, is initially required for vesicle disruption. In
      contrast, bafilomycin A1 did not prevent plasma membrane blebbing, indicating
      that the blebs are formed independently of the vesicle disruption. Acute cell
      death was inhibited by treatment with bafilomycin A1 before but not after AO
      loading. Thus, AO- and blue light-induced acute cell death is associated with
      vesicle disruption rather than bleb formation. Both the vesicle disruption and
      the formation of plasma membrane blebs were inhibited by removal of oxygen from
      the cell environment and by singlet oxygen scavengers, sodium azide, ascorbic
      acid, and L-histidine, but not inhibited by the hydroxyl radical scavenger
      dimethyl thiourea. Acute cell death was also prevented by singlet oxygen
      scavengers but not by dimethyl thiourea. Thus, these phenomena are likely caused
      at least in part by the generation of singlet oxygen. The photosensitive features
      of plasma and vesicle membranes observed in the present study may be based on the
      use of the photodynamic effect, such as cancer therapy.

PMID- 16982199
TI  - Anti-inflammatory cytokines in gingival crevicular fluid in patients with
      periodontitis and rheumatoid arthritis: a preliminary report.
AB  - Cytokines which are produced by host cells play an important role in pathogenesis
      both rheumatoid arthritis (RA) and chronic periodontitis (CP). In this study, we
      aim to investigate the levels of Interleukin (IL)-4 and IL-10 in gingival
      crevicular fluid (GCF). Seventeen patients with CP, 17 patients with RA and 17
      healthy controls (HC) were included. The RA group was divided into two groups
      according to gingival sulcus depths (RA-a: PD < or =3mm, (n=12), RA-b: PD>3mm,
      (n=5)). For each patient, clinical parameters were recorded. The GCF samples were
      evaluated by enzyme-linked immunosorbent assay (ELISA) for IL-4 and IL-10 levels.
      IL-4 levels in the RA-a, RA-b and CP subjects were significantly lower compared
      to the HC subjects (p<0.05). The mean level of IL-4 in RA-b group was
      significantly higher than that in CP group (p<0.05). IL-10 mean level in the HC
      group was higher than those in the other groups (p<0.05). In the RA-a group,
      higher IL-10 level was found compared to the CP patients (p<0.05). Within the
      limitations of this preliminary report, it can be concluded that the initiation
      and progression of periodontal inflammation may be due to a lack or inappropriate
      response of the anti-inflammatory cytokines in both CP and RA.

PMID- 16982200
TI  - New high fidelity polymerases from Thermococcus species.
AB  - Two DNA polymerase genes have been isolated from Thermococcus strains,
      Thermococcus zilligii from New Zealand, and the other, Thermococcus 'GT', a fast
      growing strain isolated from the Galapagos trench. Both genes were isolated by
      genomic walking PCR, a technique that does not require expression of the gene
      product. Phylogenetic analysis of SSU rDNA showed that the two strains were not
      closely related, as confirmed by an examination of the DNA polymerase sequences.
      Inteinless versions of each gene were generated by overlap-extension PCR and
      transferred into plasmid expression vectors. The proteins were produced in an
      Escherichia coli strain with additional copies of tRNAs corresponding to rarely
      used codons and purified by standard chromatographic procedures. Both enzymes
      were able to support PCR, but the Thermococcus 'GT' polymerase required higher
      concentrations of template than the enzyme from T. zilligii. Both enzymes showed
      3' to 5' exonuclease activity, which was abolished in the case of T. zilligii by
      mutating the aspartic acid at position 141 and the glutamic acid at position 143
      to alanine. Both enzymes showed a significant increase in fidelity of replication
      compared to the family A Thermus aquaticus DNA polymerase, in agreement with
      other results reported for family B polymerases with proof-reading ability.

PMID- 16982201
TI  - Bacterial expression and purification of the ovine type II bone morphogenetic
      protein receptor ectodomain.
AB  - Bone morphogenetic proteins (BMPs) are essential for a wide range of
      developmental processes. They signal through type I and type II serine/threonine
      kinase receptors, and differ from other TGF-beta family members in that the type
      II receptor binds with a lower affinity than the type I. Here, we describe the
      development of various Escherichia coli expression systems for the extracellular
      domain of the ovine type II bone morphogenetic protein receptor. In order to
      facilitate disulfide bond formation and protein solubility, BMPRII was expressed
      fused to bacterial thioredoxin, which, following cleavage, could be purified
      using several chromatography steps. Although this material migrated as a single
      band in denaturing PAGE, native-PAGE indicated heterogeneity, and this protein
      could not be crystallised. When expressed alone, either containing a histidine
      tag or as an untagged protein, the receptor ectodomain was deposited as insoluble
      inclusion bodies. Protein subjected to in vitro refolding procedures exhibited
      multiple species following anion exchange chromatography and size exclusion
      chromatography, as visualised on native-PAGE. Separation of these species could
      be achieved using a MonoP chromatofocusing matrix. One of these separated
      fractions, representing about 5% of the starting material, was amenable to
      crystallisation, and furthermore exhibited biological activity. Crystals of the
      histidine-tagged form were shown to diffract weakly, whereas crystals of the
      native form grew in two different morphologies, and diffracted to a resolution of
      1.2A.

PMID- 16982202
TI  - Striatal dopamine release during performance of executive functions: A [(11)C]
      raclopride PET study.
AB  - To date, while the contribution of the striatum in executive processes is well
      documented, the role played by striatal dopamine during tasks requiring executive
      functions is still unknown. We used D2-dopamine receptor ligand [(11)C]
      raclopride PET in healthy subjects while performing the Montreal Card Sorting
      Task (MCST). We observed a striatal reduction in [(11)C] raclopride binding
      potential during planning of a set-shift when compared with matching according to
      an ongoing rule. These findings suggest that striatal dopamine neurotransmission
      increases significantly during the performance of specific executive processes
      confirming previous evidence of striatal activation during fMRI studies. The
      present observation may provide some insights on the origin of cognitive deficits
      underlying certain neurological disorders associated with dopamine dysfunction,
      such as Parkinson's disease.

PMID- 16982203
TI  - Mitochondrial DNA analyses of the Cape hakes reveal an expanding, panmictic
      population for Merluccius capensis and population structuring for mature fish in
      Merluccius paradoxus.
AB  - The Cape hake species, Merluccius capensis and Merluccius paradoxus are the most
      important resource of the South African and Namibian demersal fishery, but it is
      unclear whether there is a single population of each shared by both countries. We
      analysed the population structure and evolutionary history of these two species
      using the variable 5' region of the mtDNA control region for 311 specimens of M.
      capensis and 333 specimens of M. paradoxus sampled between Luderitz (southern
      Namibia) to south of Cape Point (South Africa). 107 haplotypes for M. capensis
      and eight haplotypes for M. paradoxus were recovered. AMOVA and pairwise Phi(st)
      analyses revealed no structure in M. capensis, however significant genetic
      differentiation between Namibian and South African 'populations' was detected for
      M. paradoxus. This was only restricted to mature fish older than 3 and 4 years
      and not for juvenile fish younger than 3 years. Analyses reveal that M. capensis
      has undergone population expansion (Fu's Fs=-26.65, P<0.001), possibly within the
      last 4500-23,000 years, whereas M. paradoxus has not. Our study highlights the
      utility of genetic markers to unravel the evolutionary history of sympatric
      species, as well as addressing management issues within regions where
      commercially valuable fish stocks are shared between nations.

PMID- 16982204
TI  - Cattle with thymic lymphoma and haematoma of the ventral neck: a comparison of
      findings.
AB  - The goal of the present paper was to establish criteria for the differentiation
      of thymic lymphoma and haematoma of the ventral neck in cattle. Four cattle with
      thymic lymphoma and seven with haematoma of the ventral neck underwent physical,
      haematological, biochemical and ultrasonographic examinations as well as
      histological evaluation of a biopsy specimen. All of the animals had firm non
      painful swellings, which were no warmer than normal and extended from the
      pharyngeal region to the thoracic inlet. A diagnosis could not be established
      based on the results of physical examination and palpation of the swellings.
      Animals with a haematoma had a shorter history of being ill compared to those
      with thymic lymphoma. In patients with a haematoma, anaemia was present, the
      heart rate was elevated and the haematocrit was decreased, but not in cattle with
      thymic lymphoma. A tentative diagnosis was made on the basis of a macroscopic
      evaluation of the biopsy samples, which were dark red and firm in cattle with a
      haematoma. All cases of malignant thymic lymphoma were confirmed by histological
      examination of a biopsy sample. Ultrasonography did not help to differentiate
      between haematoma and thymic lymphoma. All animals with thymic lymphoma and three
      of those with a haematoma were euthanased. The four remaining animals with a
      haematoma were treated successfully.

PMID- 16982205
TI  - Effects of radiation damping on Z-spectra.
AB  - Radiation damping induced by the strong water magnetization in Z-spectroscopy
      experiments can be sufficient to perturb significantly the resultant Z-spectrum.
      With a probe tuned to exact electrical resonance the effects are relatively
      straightforward, narrowing the central feature of the Z-spectrum. Where, as is
      commonly the case, the probe is tuned sufficiently well to give optimum signal-to
      noise ratio and radiofrequency field strength but is not at exact resonance,
      radiation damping introduces an unexpected asymmetry into the Z-spectrum. This
      has the potential to complicate the use of Z-spectrum asymmetry to study chemical
      exchange, for example in the estimation of pH in vivo.

PMID- 16982206
TI  - Spinal cord injury resulting from incorrect microchip placement in a cat.
AB  - A 2-year-old, male neutered domestic shorthair cat was presented for
      investigation of an acute onset of tetraparesis immediately following the
      implantation of a pet identification microchip. A left-sided C6-T2 spinal segment
      localisation was suspected from the neurological examination, with spinal cord
      trauma being the primary differential diagnosis. Myelography demonstrated
      obliteration of the contrast columns by the microchip at the C5-C6 intervertebral
      disc space. A dorsal laminectomy was undertaken and the microchip was
      successfully removed. Eleven months after the surgery, the cat was able to weight
      bear in all limbs but with mild residual paresis in the left thoracic limb.

PMID- 16982207
TI  - [Haemostatic hysterectomies in developing countries: A vital act. Prospective
      study in a reference Nigerian maternity].
AB  - OBJECTIVE: The purpose of our prospective study was to determine the frequency,
      the main indications and difficulties of coverage of the peripartum haemostatic
      hysterectomy in a developing country. The secondary purpose was to assess the
      maternal forecast and suggest suited management and to estimate the necessary
      material and human means to reduce the incidence of this surgery. PATIENTS AND
      METHODS: We realized a forward-looking monocentric study in the Issaka Gazobi
      maternity of Niamey, between January 1st, 2003 and December 31st, 2003. RESULTS:
      3255 deliveries took place, and 41 peripartum haemostatic hysterectomies for post
      partum haemorrhage were realized (ie 1.26%). The mean age of our patients was
      32.76. The multiparous (more than 5 children) were most often concerned. The
      majority of patients had benefited from an in utero transfer. 31 patients
      presented an active bleeding, 11 were in a state of shock during the admittance.
      The main indications of hysterectomies were represented by an abruptio haematoma,
      uterine inertia, a rupture of the uterus, a wound of the genital field, 1
      placenta accreta with uterine inversion. In a third part of the cases a
      disseminated intravascular coagulation was associated to the clinical picture.
      The hysterectomy was subtotal in most of the cases. Finally, the rate of maternal
      death is high in our series. DISCUSSION AND CONCLUSION: Prevention of post-partum
      haemostatic haemorrhage and new therapeutic strategies are essential to reduce
      the rate of haemostatic hysterectomy in our regions, and improve the coverage of
      this pathology. However, it is a vital surgery which must be technically
      mastered.

PMID- 16982208
TI  - Raman spectrum, quantum mechanical calculations and vibrational assignments of
      (95% alpha-TeO2/5% Sm2O3) glass.
AB  - Chozen system of tellurite glasses doped with rare earth oxides (95% alpha
      TeO(2)+5% Sm2O3) was prepared by melt quenching. Consequently, the Raman spectrum
      (150-1250 cm(-1)) of the modified tellurite have been recorded. As a continuation
      to our normal coordinate analysis, force constants and quantum mechanical (QM)
      calculations for tbp TeO4(4-) (triagonal bipyramid, C(2v)) and TeO(3+1); Te2O7(6
      ) (bridged tetrahedral), we have carried out ab initio frequency calculations for
      tpy TeO3(2-) (triagonal pyramidal, C(3v) and C(s)) and tp TeO3(2-) (triagonal
      planar, D(3h)) ions. The quantum mechanical calculations at the levels of RHF,
      B3LYP and MP2 allow confident vibrational assignments and structural
      identification in the binary oxide glass (95% alpha-TeO2 +5% Sm2O3). The dominant
      three-dimensional network structures in the modified glass are triagonal
      pyramidal TeO3 with minor features of short range distorted tbp TeO4 and bridged
      tetrahedral unit of TeO(3+1), leading to a structure of infinite chain.
      Therefore, alpha-TeO2/Sm2O3 (95/5%) glass experience structural changes from TeO4
      (tbp); Te2O7 (TeO(3+1))-->TeO3 (tpy).

PMID- 16982209
TI  - Molecular and epidemiologic analysis of enterovirus B neurological infection in
      Argentine children.
AB  - BACKGROUND: Human enteroviruses are one of the major causes of central nervous
      system (CNS) infections in pediatrics. STUDY DESIGN: We have studied 1242
      children under 15 years old with suspicion of CNS infection from January 1998 to
      December 2003. CSF was obtained and molecular typing of human enterovirus B
      serotypes was performed by RT-PCR and sequencing of the N-terminal part of VP1
      gene. RESULTS: According to the clinical syndromes, patients were grouped as
      aseptic meningitis (n=654, 52.6%), encephalitis (n=239, 19.2%), febrile seizures
      (n=153, 12.3%), febrile infant (n=84, 6.7%), neonatal disease (n=70, 5.6%),),
      acute flaccid paralysis (n=31, 2.4%) and acute disseminated encephalomyelitis
      (n=11, 0.9%). HEV was detected in 335/1242 CSF samples (26.97%) and was
      associated to aseptic meningitis (n=243, 72.5%); febrile infant (n=31, 9.2%);
      neonatal infection (n=26, 7.7%); encephalitis (n=25, 7.5%), febrile seizures
      (n=9, 2.68%); acute flaccid paralysis (n=1, 0.3%). Seasonal incidence of HEV-B
      species was analyzed showing that in Buenos Aires infections occur mainly during
      late spring and summer. Molecular serotyping was completed in 60/335 samples.
      Echovirus 30, Echovirus 9, Coxsackie B3 to B5 and Echovirus 33 were the most
      frequently identified. CONCLUSIONS: We showed that HEV are responsible for a
      considerable proportion of hospitalizations in children with central nervous
      system compromise reaching 27% of overall etiology.

PMID- 16982210
TI  - LDL receptor gene transcription is selectively induced by t10c12-CLA but not by
      c9t11-CLA in the human hepatoma cell line HepG2.
AB  - Conjugated linoleic acids (CLA) have attracted scientific interest due to their
      potential beneficial effects on atherosclerosis. Recently, a mixture of CLA
      isomers was demonstrated to upregulate LDL receptor expression in the human
      hepatoma cell line HepG2. However, the underlying mechanisms remain to be
      resolved. Thus, the aim of this study was to elucidate how CLA mediates
      upregulation of LDL receptor in HepG2 cells and whether this upregulation is
      isomer-specific. The results revealed that LDL receptor promoter activity and
      mRNA expression were strongly induced upon treatment with t10c12-CLA (P<0.05),
      whereas c9t11-CLA and linoleic acid (LA) had no effect. In addition, only
      treatment with t10c12-CLA markedly induced mRNA expression of SREBP-2 and HMG-CoA
      reductase and slightly induced that of SREBP-1 (P<0.05). Using SREBP-2 knockdown
      cells, we could demonstrate that the effect of t10c12-CLA on LDL receptor gene
      transcription was significantly reduced when compared to control cells (P<0.05).
      When using SREBP-1 knockdown cells the effect of t10c12-CLA on LDL receptor mRNA
      only slightly decreased compared to control cells. In addition, using different
      deletion constructs of the LDL receptor gene promoter we showed that the
      induction of the LDL receptor by t10c12-CLA is independent of the AP-1 motif in
      the LDL receptor promoter. In conclusion, the present study revealed that
      transcriptional activation of the LDL receptor gene by t10c12-CLA is dependent on
      the upregulation of SREBP-2 and is probably due to the activation of the SRE-1 in
      the LDL receptor gene promoter in HepG2 cells. Thus, the decreased plasma
      cholesterol levels in response to CLA as observed in a limited number of animal
      and human studies might be explained by an enhanced uptake of VLDL and LDL
      cholesterol via hepatic LDL receptors. However, it provides no explanation for
      the outcome of most human studies reporting unaltered or even increased plasma
      and LDL cholesterol concentrations in response to supplementation with CLA.

PMID- 16982211
TI  - Ubiquitin: tool and target for intracellular NF-kappaB inhibitors.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) has a pivotal role in
      initiating inflammation and raising an effective immune response. Because NF
      kappaB activation depends on ubiquitination, cells have developed ubiquitin (Ub)
      mediated strategies for inhibiting NF-kappaB activation and preventing excessive
      inflammation. Recent findings concerning tumor necrosis factor (TNF) receptor and
      toll-like receptor (TLR)-interleukin-1 (IL-1) receptor signalling pathways show
      that Ub can be a tool as well as a target for NF-kappaB inhibitory proteins,
      either by labelling specific signalling proteins for proteasome-dependent
      degradation or by serving as a target for specific de-ubiquitinating enzymes that
      prevent the formation of pertinent signalling complexes. Interfering with
      ubiquitination therefore seems to be a versatile means for regulating NF-kappaB
      activity, indicating that studies of Ub-mediated signalling might hold the key
      for developing new therapeutic strategies for inflammatory disease.

PMID- 16982212
TI  - Protein model refinement using structural fragment tessellation.
AB  - A method is described for the refinement of rough protein models based on finding
      a selection of structural fragments that match the model. Unlike most fragment
      based methods, these are not necessarily contiguous in the sequence and form a
      tiling (tessellation) that covers most of the structure. The residue positions of
      the fragments are then used as a target for the model atoms to generate a revised
      model which is used as the basis of a subsequent pattern definition and search.
      The method was shown to improve the recognition of the native fold in a series of
      decoys largely as a result of improved secondary structure representation.

PMID- 16982213
TI  - Defect internalization and tyrosine kinase activation in Aire deficient antigen
      presenting cells exposed to Candida albicans antigens.
AB  - Patients with Autoimmune polyendocrine syndrome type I (APS I) present with
      multiple endocrine failures due to organ-specific autoimmune disease, thought to
      be T-cell-mediated. Paradoxically, APS I patients suffer from chronic
      mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune
      regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus
      and in antigen presenting cells in the periphery. T cells from Aire deficient
      mice and men displayed an enhanced proliferative response against Candida antigen
      in vitro, suggesting that Aire deficient T cells are competent in recognizing
      Candida albicans. In contrast, monocytes from APS I patients displayed a
      decreased and delayed internalization of zymosan. Furthermore, Candida antigen
      activated monocytes from APS I patients show decreased and altered phoshotyrosine
      kinase activation. In conclusion, Aire deficient APCs have a defect receptor
      mediated internalization of Candida which affects kinase activation, likely
      altering the innate Candida immune response.

PMID- 16982214
TI  - Rheumatoid synovial fluid T cells are sensitive to APO2L/TRAIL.
AB  - The infiltration and accumulation of T cells in the rheumatoid arthritis (RA)
      synovial fluid (SF) are hallmarks of disease. We aimed to assess the functional
      relevance of FasL and of APO2L/TRAIL in the persistence of T cells in the
      rheumatoid SF. We have analyzed the expression of the activation markers HLA-DR
      and CD69 and also of the death receptor Fas/CD95 and death ligands FasL or
      APO2L/TRAIL in CD3+ lymphocytes from SF of 62 RA patients, together with their
      sensitivity to anti-Fas mAb or to rAPO2L/TRAIL, using as controls T lymphocytes
      present in SF of 20 patients with traumatic arthritis. T lymphocytes infiltrated
      in SF of RA patients have a chronically activated phenotype, but they are
      resistant to Fas-induced toxicity. However, they are more susceptible to
      rAPO2L/TRAIL than T cells in the SF of traumatic arthritis patients. In addition,
      we found very low amounts of bioactive FasL and APO2L/TRAIL associated with
      exosomes in SF from RA patients as compared with SF from traumatic arthritis
      patients. The observation on the sensitivity of RA SF T cells to rAPO2L could
      have therapeutic implications because bioactive APO2L/TRAIL could be beneficial
      as a RA treatment.

PMID- 16982215
TI  - Long-term monitoring of transplanted islets using positron emission tomography.
AB  - Islet transplantation can restore glucose homeostasis in those with type 1
      diabetes; however, most recipients eventually lose graft function. A noninvasive
      method to monitor islets following transplantation would enable assessment of
      their survival and aid the development of therapeutics to prolong graft survival.
      Here, we show that recombinant lentivirus can be used to engineer human islets to
      express a positron emission tomography (PET) reporter gene. Following
      transplantation into mice, transduced islets could be imaged in vivo using
      microPET and a radiolabeled probe approved by the FDA for clinical use in humans.
      The magnitude of signal from engineered islets implanted into the axillary cavity
      reflected the implanted islet mass. Signals from implanted islets decreased by
      approximately one-half during the first few weeks following transplantation,
      which may reflect islet cell death shortly after transplantation. Thereafter, the
      magnitude of signals from the implanted islets remained fairly constant when the
      recipients were repetitively reimaged over 90 days. Histological analysis of the
      implants showed healthy islets with PET reporter-expressing cells distributed
      throughout the islet architecture. These studies suggest that PET imaging of
      lentivirus-transduced islets could provide a safe and feasible method for long
      term monitoring of islet graft survival.

PMID- 16982216
TI  - The MitoDrome database annotates and compares the OXPHOS nuclear genes of
      Drosophila melanogaster, Drosophila pseudoobscura and Anopheles gambiae.
AB  - The oxidative phosphorylation (OXPHOS) is the primary energy-producing process of
      all aerobic organisms and the only cellular function under the dual control of
      both the mitochondrial and the nuclear genomes. Functional characterization and
      evolutionary study of the OXPHOS system is of great importance for the
      understanding of many as yet unclear aspects of nucleus-mitochondrion genomic co
      evolution and co-regulation gene networks. The MitoDrome database is a web-based
      database which provides genomic annotations about nuclear genes of Drosophila
      melanogaster encoding for mitochondrial proteins. Recently, MitoDrome has
      included a new section annotating genomic information about OXPHOS genes in
      Drosophila pseudoobscura and Anopheles gambiae and their comparative analysis
      with their Drosophila melanogaster and human counterparts. The introduction of
      this new comparative annotation section into MitoDrome is expected to be a useful
      resource for both functional and structural genomics related to the OXPHOS
      system.

PMID- 16982217
TI  - Development of an enzymatic DNA repair assay for molecular epidemiology studies:
      distribution of OGG activity in healthy individuals.
AB  - While the role of reduced DNA repair in susceptibility to hereditary cancers is
      well established, its role in sporadic cancer is less understood. One of the
      reasons is the lack of specific DNA repair assays that are suitable for
      epidemiology studies. Here we describe the development of the OGG test, an
      epidemiology-grade enzymatic assay for the activity of the base excision repair
      enzyme 8-oxoguanine DNA glycosylase, in protein extracts prepared from human
      blood cells. The assay is robust and reproducible, with a coefficient of
      variation of 10%. Using the OGG test we determined OGG activity in 120 healthy
      individuals. Our results show an inter-individual variation of 2.8-fold in OGG
      activity, from 3.6 up to 10.1units/microg protein, with a mean value of
      7.2units/microg protein. There was no significant difference in OGG activity
      between males and females, or between smokers and non-smokers. Interestingly,
      there was a gender-specific effect of age: OGG activity was slightly but
      significantly lower in males older than the age of 55 years compared to younger
      males, but not in females at the same age groups. Analysis of OGG1 mRNA by
      quantitative real-time RT-PCR showed a group trend of an increase in OGG
      enzymatic activity with increasing mRNA expression, but the correlation between
      activity and mRNA in individuals was poor, indicating the importance of factors
      other than mRNA expression. The OGG test described is expected to be useful in
      studying the role of 8-oxoguanine repair in cancer, as recently demonstrated for
      non-small cell lung cancer [T. Paz-Elizur, M. Krupsky, S. Blumenstein, D.
      Elinger, E. Schechtman, Z. Livneh, J. Natl. Cancer Inst. 95 (2003) 1312-1319]. In
      addition, it may serve as a paradigm for the development of additional functional
      DNA repair tests, which are needed in order to gain further insight into the role
      of DNA repair in cancer risk and pathology.

PMID- 16982219
TI  - Restless leg syndrome manifested by iron deficiency from chronic hemoptysis in
      cystic fibrosis.
AB  - Restless leg syndrome (RLS) and periodic limb movement disorder (PLMD) are
      considered to be a continuum of a neurological sleep disorder associated with
      abnormal iron metabolism or deficiency. I describe a case of RLS and PLMD in a
      cystic fibrosis patient with iron deficiency from chronic hemoptysis. This is the
      first case that reports RLS and PLMD manifesting from iron deficiency caused by
      chronic hemoptysis in advanced cystic fibrosis lung disease.

PMID- 16982218
TI  - NEIL2-initiated, APE-independent repair of oxidized bases in DNA: Evidence for a
      repair complex in human cells.
AB  - DNA glycosylases/AP lyases initiate repair of oxidized bases in the genomes of
      all organisms by excising these lesions and then cleaving the DNA strand at the
      resulting abasic (AP) sites and generate 3' phospho alpha,beta-unsaturated
      aldehyde (3' PUA) or 3' phosphate (3' P) terminus. In Escherichia coli, the AP
      endonucleases (APEs) hydrolyze both 3' blocking groups (3' PUA and 3' P) to
      generate the 3'-OH termini needed for repair synthesis. In mammalian cells, the
      previously characterized DNA glycosylases, NTH1 and OGG1, produce 3' PUA, which
      is removed by the only AP-endonuclease, APE1. However, APE1 is barely active in
      removing 3' phosphate generated by the recently discovered mammalian DNA
      glycosylases NEIL1 and NEIL2. We showed earlier that the 3' phosphate generated
      by NEIL1 is efficiently removed by polynucleotide kinase (PNK) and not APE1. Here
      we show that the NEIL2-initiated repair of 5-hydroxyuracil (5-OHU) similarly
      requires PNK. We have also observed stable interaction between NEIL2 and other
      BER proteins DNA polymerase beta (Pol beta), DNA ligase IIIalpha (Lig IIIalpha)
      and XRCC1. In spite of their limited sequence homology, NEIL1 and NEIL2 interact
      with the same domains of Pol beta and Lig IIIalpha. Surprisingly, while the
      catalytically dispensable C-terminal region of NEIL1 is the common interacting
      domain, the essential N-terminal segment of NEIL2 is involved in analogous
      interaction. The BER proteins including NEIL2, PNK, Pol beta, Lig IIIalpha and
      XRCC1 (but not APE1) could be isolated as a complex from human cells, competent
      for repair of 5-OHU in plasmid DNA.

PMID- 16982220
TI  - Facial nerve palsy associated with a low serum vitamin A level in an infant with
      cystic fibrosis.
AB  - A previously healthy 10-week-old infant presented with isolated unilateral facial
      nerve paralysis which progressed to bilateral paralysis over a 2-week period.
      Evaluation including MRI and CT of the brain and facial nerve, CSF evaluation and
      EMG yielded no diagnosis. A single F508 gene mutation on the newborn screen
      prompted sweat chloride testing which confirmed a diagnosis of cystic fibrosis.
      On measurement of fat-soluble vitamins, levels of vitamin A were approximately
      10% of the lower normal range, in the absence of objective evidence of
      pseudotumor cerebri. This case emphasizes an important association between
      hypovitaminosis A, cystic fibrosis and facial nerve palsy.

PMID- 16982221
TI  - Selective inhibition of ion transport mechanisms regulating intracellular pH
      reduces proliferation and induces apoptosis in cholangiocarcinoma cells.
AB  - BACKGROUND: Cells within the acidic extracellular environment of solid tumours
      maintain their intracellular pH through the activity of the Na(+)/H(+) exchanger
      and the Na(+) dependent Cl(-)/HCO(3)(-) exchanger. The inhibition of these
      mechanisms could therefore inhibit cancer cell growth. AIM: We evaluated the
      effect of two selective inhibitors of these transporters (cariporide and S3705)
      on proliferation and apoptosis of human cholangiocarcinoma cells (HUH-28 and Mz
      ChA-1 cells) as a function of external pH (7.4 and 6.8). METHODS/RESULTS: HUH-28
      cells incubated for 24h at external pH 7.4 or 6.8 without inhibitors maintained
      intracellular pH at physiological level, whereas incubation with cariporide
      and/or S3705 caused the intracellular pH of cells to drop. Incubation of HUH-28
      cells with cariporide and/or S3705 was able to reduce proliferation, evaluated by
      a colorimetric ELISA method, and to induce apoptosis, evaluated by measuring
      caspase-3 activity and Annexin-V staining, and these effects were more evident at
      external pH 6.8. S3705 but not cariporide was able to inhibit serum-induced
      phosphorylation of ERK1/2, AKT and BAD, intracellular molecules involved in
      cancer cell proliferation and survival. Similar results were obtained in Mz-ChA-1
      cells. CONCLUSIONS: (1) Inhibition of intracellular pH regulatory mechanisms by
      cariporide and S3705 reduces proliferation and induces apoptosis in
      cholangiocarcinoma cells; and (2) these drugs might have potential therapeutic
      value against cholangiocarcinoma.

PMID- 16982222
TI  - Lack of correlation of degree of villous atrophy with severity of clinical
      presentation of coeliac disease.
AB  - BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal
      damage in coeliac disease vary greatly. In view of conflicting information as to
      whether the mode of presentation correlates with the degree of villous atrophy,
      we reviewed a large cohort of patients with coeliac disease. PATIENTS AND
      METHODS: We correlated mode of presentation (classical, diarrhoea predominant or
      atypical/silent) with histology of duodenal biopsies and examined their trends
      over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68%
      females. The majority had silent coeliac disease (56%) and total villous atrophy
      (65%). There was no correlation of mode of presentation with the degree of
      villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a
      severe villous atrophy (p=0.052). There was a significant trend over time for a
      greater proportion of patients presenting as atypical/silent coeliac disease and
      having partial villous atrophy, though the majority still had total villous
      atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in
      duodenal biopsies did not correlate with the mode of presentation, indicating
      that factors other than the degree of villous atrophy must account for diarrhoea
      in coeliac disease.

PMID- 16982224
TI  - HPV vaccines: now that they're here, how do we maximize their benefit?

PMID- 16982223
TI  - A case of oncogenic osteomalacia with preoperative secondary hyperparathyroidism:
      description of the biochemical response of FGF23 to octreotide therapy and
      surgery.
AB  - Oncogenic osteomalacia is a rare condition characterized by a low serum
      phosphate, reduced tubular reabsorption of phosphate and a low or inappropriately
      normal 1,25 dihydroxyvitamin D and is usually secondary to a phosphaturic
      mesenchymal tumor. Complete tumor resection results in resolution of all
      features. We report a patient with oncogenic osteomalacia and concurrent
      secondary hyperparathyroidism. Serum phosphate failed to normalize preoperatively
      with octreotide therapy, although this treatment did suppress serum FGF23. The
      postoperative course was distinguished by marked hyperphosphatemia that was
      associated with elevated serum 1,25 dihydroxyvitamin D concentrations.

PMID- 16982225
TI  - The Cochrane Fertility Regulation Group: synthesizing the best evidence about
      family planning.
AB  - The Fertility Regulation Group of the Cochrane Collaboration has been assessing
      the best available evidence on fertility regulation, family size and birth
      spacing. By the end of 2005, this group had published 32 systematic reviews and
      12 protocols; most reviews were on contraception. Because of suboptimal trial
      quality, firm conclusions could be made in only five reviews. Threats to internal
      validity in published trials include the absence of description of allocation
      concealment, intentional exclusion of participants after randomization, failure
      to use intention-to-treat analyses and lack of treatment blinding. The precision
      of results has been limited by small sample sizes. The finding that most trials
      of oral contraceptives were conducted by pharmaceutical companies raises concerns
      about potential commercial bias. Of necessity, most information about fertility
      regulation effectiveness and adverse effects comes from observational studies,
      which vary widely in quality. Systematic reviews of evidence, with an emphasis on
      randomized controlled trials when available, will continue to improve fertility
      regulation in the years ahead.

PMID- 16982226
TI  - Continuation rates of Implanon in the UK: data from an observational study in a
      clinical setting.
AB  - BACKGROUND: Long-acting reversible methods of contraception can potentially
      reduce unintended pregnancy. There are few data on "real-life" continuation rates
      of the contraceptive implant Implanon. MATERIALS AND METHODS: Three hundred
      twenty-four women choosing Implanon in a community family planning clinic in
      Scotland were followed up by case note review (n=236) or postal questionnaire
      (n=87) 3 years after insertion of the implant (1 woman chose not to disclose her
      home address). RESULTS: Data were available for 85% of the women. Continuation
      rates were 89% (CI 84-91) at 6 months, 75% (CI 69-79) at 1 year, 59% (CI 52-63)
      at 2 years and 47% (CI 40-52) at 2 years and 9 months. Of the 68 women who
      discontinued Implanon within 1 year, 62 (91%) did so because of unwanted side
      effects, the most common being frequent and/or unpredictable bleeding (n=42,
      62%). Almost half changed to a less-effective method of contraception; however,
      one third (n=99, 39%) chose to use a second implant when the first one expired.
      CONCLUSIONS: Continuation rates of Implanon in this clinic setting in the UK make
      it a cost-effective method of contraception and justify its widespread provision.

PMID- 16982227
TI  - Cerebral venous sinus thrombosis in users of four hormonal contraceptives:
      levonorgestrel-containing oral contraceptives, norgestimate-containing oral
      contraceptives, desogestrel-containing oral contraceptives and the contraceptive
      patch.
AB  - BACKGROUND: It has been suggested that the risk for cerebral venous sinus
      thrombosis (CVST) may be greater among users of the contraceptive patch than
      among users of oral contraceptives (OCs). METHODS: From the PharMetrics database,
      we identified women aged 15-44 years who filled at least one prescription for
      either the contraceptive patch or desogestrel-containing, norgestimate-containing
      or levonorgestrel-containing OCs to assess the risk of CVST. The person-time of
      current exposure to each study drug, as well as the incidence rates (IRs) and
      incidence rate ratios (IRRs) of CVST, was calculated. RESULTS: We identified over
      1 million users of the four study drugs. There were five cases of CVST among
      current users of desogestrel, seven cases among current users of norgestimate,
      two cases among current users of levonorgestrel and none among current users of
      the contraceptive patch. The IRs per 100,000 woman-years were 2.7 [95% confidence
      interval (95% CI)=0.9-6.3], 1.6 (95% CI=0.7-3.3), 0.7 (95% CI=0.1-2.4) and 0.0
      (95% CI=0.0-4.8), respectively, in users of desogestrel, norgestimate,
      levonorgestrel and the contraceptive patch. There were two women who had CVST
      while not currently taking a hormonal contraceptive (IR=0.4 per 100,000 woman
      years; 95% CI=0.1-1.3). The IRRs were 4.0 (95% CI=0.7-42.4) for desogestrel
      containing versus levonorgestrel-containing OCs, and 2.4 (95% CI=0.5-24.0) for
      norgestimate-containing versus levonorgestrel-containing OCs. The IRR for the
      patch could not be calculated. CONCLUSIONS: There is no evidence of an increased
      risk of CVST in users of the contraceptive patch compared to users of
      levonorgestrel-containing OCs.

PMID- 16982228
TI  - Effects of transdermal and oral contraceptives on estrogen-sensitive hepatic
      proteins.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of the
      contraceptive patch and an oral contraceptive (OC) on serum concentrations of
      estrogen-sensitive hepatic proteins, ethinyl estradiol (EE) and levonorgestrel
      (LNG). METHODS: Twenty-four women were randomized to receive three cycles of a
      contraceptive patch that delivers EE 20 microg/day and norelgestromin 150
      microg/day or an OC that contains EE 35 microg and norgestimate 250 microg. Blood
      samples were taken at baseline and at the end of Cycle 3. Serum levels of sex
      hormone-binding globulin (SHBG), thyroxine-binding globulin (TBG), corticosteroid
      binding globulin (CBG) and C-reactive protein (CRP) were quantified by
      immunoassay methods. EE and LNG levels in patch users were measured by
      radioimmunoassay (RIA) and liquid chromatography-tandem mass spectrometry (LC
      MS/MS) assay. The paired t test and Student's t test were used for statistical
      analysis. RESULTS: Nineteen women completed the study (patch, n=10; OC, n=9).
      Treatment with both the patch and OC resulted in significant increases from
      baseline in SHBG, TBG and CBG. The increase in CRP was significant in the patch
      group and approached significance in the OC group. The increases in SHBG and TBG
      observed with the patch were significantly greater than those associated with the
      OC. By way of RIA and LC-MS/MS assay methods, the patch was associated with mean
      EE levels of 114 and 111 pg/mL, respectively. CONCLUSIONS: The serum
      concentrations of estrogen-sensitive hepatic proteins and EE associated with the
      patch suggest that this new contraceptive system may have relatively large net
      estrogen effects.

PMID- 16982229
TI  - Effects of the long-term use of depot medroxyprogesterone acetate as hormonal
      contraceptive on bone mineral density and biochemical markers of bone remodeling.
AB  - PURPOSE AND METHOD: Our objective is to evaluate the effects of the long-term use
      of depot medroxyprogesterone acetate (DMPA) as a method of contraception on bone
      mineral density (BMD) and bone remodeling. Forty women (21-44 years old) who used
      DMPA for contraception for <1, 1-2 and >5 years, in addition to 20 age-matched
      healthy women (nonusers), participated in this study. Lumbar spine BMD (LS-BMD)
      was measured by dual-energy X-ray absorptionmetry. Serum osteocalcin (OC), a bone
      formation marker, was measured by enzyme amplification sorbent immunoassay.
      Urinary deoxypyridinoline (DPD), a bone resorption marker, was determined by
      enzyme immunoassay. RESULTS: Serum OC and urinary DPD levels in women who used
      DMPA for <1, 1-2 and >5 years were significantly increased compared to the
      corresponding levels in nonusers. The increase of both biomarkers was more
      pronounced with longer duration of use. LS-BMD was significantly decreased in
      women on long-term DMPA use compared to LS-BMD in nonusers. The mean percentage
      decrease of LS-BMD in women who used DMPA for 1-2 and >5 years was 9% and 11.8%,
      respectively. LS-BMD was negatively correlated with serum OC and urinary DPD in
      women who used DMPA. On the other hand, LS-BMD and bone turnover were not
      significantly different between women who used DMPA for <1 year and nonusers.
      CONCLUSION: Long-term use of DMPA (>2 years) had a significant adverse effect on
      BMD and induced increased bone turnover, as evidenced by a significant increase
      in biochemical indices of bone formation and resorption. The measurement of LS
      BMD and of biomarkers of bone turnover may be recommended in women aged above 40
      years and who used DMPA for a long duration (2-5 years).

PMID- 16982230
TI  - ORTHO birth control satisfaction assessment tool: assessing sensitivity to change
      and predictors of satisfaction.
AB  - OBJECTIVE: To test the sensitivity to change of the ORTHO Birth Control
      Satisfaction Assessment Tool (ORTHO BC-SAT) among dissatisfied women switching to
      a new hormonal birth control method and to better understand which factors
      contribute to a woman's satisfaction with the method. MATERIALS AND METHODS:
      Women switching to a new hormonal birth control method [oral contraceptives
      (OCs), injections, vaginal ring or transdermal patch] completed the ORTHO BC-SAT,
      a questionnaire measuring satisfaction, two times over a 3-month period.
      Sensitivity to change was measured by examining change scores, as well as the
      Guyatt's statistic. Predictors of satisfaction were examined using forward
      stepping linear regression. RESULTS: Fifty-six women completed the ORTHO BC-SAT
      twice. With the exception of Future Fertility Concerns, women reported
      statistically significant improvements on all scales of the questionnaire. The
      scales most sensitive to change were Overall Satisfaction, Assurance/Confidence,
      Lifestyle Impact, and Ease of Use/Convenience. Being older, switching from a
      nonhormonal method of birth control at baseline and more bodily pain at baseline
      predicted the increase in satisfaction scales. CONCLUSION: The ORTHO BC-SAT has
      demonstrated sensitivity to change in this population. In addition, we identified
      several factors at baseline that predicted an increase in satisfaction scale
      scores.

PMID- 16982231
TI  - Sociodemographic and sexual health profile of users of emergency hormonal
      contraception: data from a British probability sample survey.
AB  - OBJECTIVE: This study aimed to identify factors associated with the use of
      emergency hormonal contraception (EHC). METHODS: Data from a probability sample
      survey of 12,110 men and women aged 16-44 living in Britain were used for this
      study; 5916 women were selected as potential users of EHC, defined as women
      reporting at least one male partner in the year prior to the survey. RESULTS: Of
      the 5916 women, 2.3% reported EHC use in the previous year. EHC use was more
      common among younger, single women, those with more than one sexual partner in
      the past year and those using condoms for contraception. It was significantly
      associated with experience of abortion (odds ratio adjusted for age, marital
      status and number of male partners: 2.40) but not with sexually transmitted
      infection (STI) diagnosis. CONCLUSIONS: The use of EHC identifies a group of
      women at increased risk of unplanned pregnancy and condom use but not STI
      acquisition. Provision of information on more reliable contraceptive methods is
      needed to reduce the risk of unplanned pregnancy recurrence.

PMID- 16982232
TI  - Survey of attitudes regarding natural family planning in an urban Hispanic
      population.
AB  - METHODS: We performed a cross-sectional survey of 357 reproductive-aged women,
      mostly Hispanic (81.8%), presenting for ambulatory and hospital reproductive care
      in Phoenix, AZ, about their interest in natural family planning (NFP).
      Participants completed questionnaires, and responses were analyzed to determine
      predictors of interest in NFP. RESULTS: Sixty-one percent stated that they were
      likely or very likely to use NFP to avoid pregnancy, and 50% would use NFP to
      achieve pregnancy. Of factors studied, Hispanic ethnicity, lower level of
      acculturation, less education and recent use of condoms or withdrawal were
      independently associated with interest in using NFP to avoid pregnancy. Younger
      age and desire for future pregnancy were independently predictive of potential
      NFP use to achieve pregnancy. CONCLUSION: This study suggests that Hispanic women
      find NFP to be an appealing family planning alternative.

PMID- 16982233
TI  - Utilization of contraception and abortion and its relationship to HIV infection
      among female sex workers in Tashkent, Uzbekistan.
AB  - OBJECTIVE: This study aimed to describe reported contraceptive and abortion
      utilization and their relationship to human immunodeficiency virus (HIV)
      infection among female sex workers (FSW) in Tashkent, Uzbekistan. METHODS: For
      this cross-sectional study, women were recruited through outreach workers
      affiliated with Istiqbolli Avlod. Participants completed a self-administered
      questionnaire and underwent HIV testing. RESULTS: Of 448 participants, the
      majority (86.2%, n=386) used contraception; 39.6% reported inconsistent use.
      Methods most frequently utilized were condoms (50.9%) and intrauterine devices
      (16.1%). One fourth (24.3%, n=109) reported multiple (>or=3) prior abortions.
      Inconsistent contraceptive users were more likely to be infected with HIV
      (AOR=2.72, 95% CI=1.19-6.22), but such infection was not related to a specific
      contraceptive method, including condoms, or utilization of abortion. CONCLUSIONS:
      Inconsistent contraceptive use is common and may be a predictor of HIV infection
      among Tashkent FSW. Factors preventing consistent contraceptive use may be
      related to HIV risk and require further study in this population.

PMID- 16982234
TI  - The use of vaginal misoprostol for second-trimester pregnancy termination in
      women with previous single cesarean section.
AB  - INTRODUCTION: This retrospective study reports of 85 women in the second
      trimester with one prior cesarean section undergoing medical abortion of a viable
      unwanted pregnancy using vaginal misoprostol. Two regimens that were selected in
      a nonrandomized manner were used. MATERIALS AND METHODS: Eighty-five women
      treated with vaginal misoprostol in a 3-year period were retrospectively
      analyzed. All received 400 mug of misoprostol initially and 22 (25.8%) aborted.
      Then Group A (n=43) received subsequent administration of 200 microg every 6 h,
      whereas Group B (n=20) received 400 microg/6 h. RESULTS: All patients aborted.
      The groups had no statistical difference in mean age, gravidity, parity,
      gestational age, and time from previous cesarean section, and there was no
      difference in occurrence of side effects and mean induction to abortion time
      interval. The lower dosage group received a median of 600 microg of vaginal
      misoprostol (min 600 microg to max 1000 microg). There were no uterine ruptures,
      need for hysterotomy, or excess bleeding in any patient. CONCLUSIONS: This is the
      largest series reported to date of second-trimester pregnancy termination in
      cases with one previous cesarean section using only vaginal misoprostol. The
      study shows that both used regimens are safe and equally effective. All 85 women
      aborted.

PMID- 16982235
TI  - Sublingual versus vaginal misoprostol (400 microg) for cervical priming in first
      trimester abortion: a randomized trial.
AB  - OBJECTIVE: Our objective was to compare the sublingual administration and the
      vaginal administration of misoprostol for cervical priming before first-trimester
      surgical abortion. DESIGN: We used an open, multicenter, randomized trial.
      LOCATIONS: We conducted the study in four clinics (in Valencia, Castello, Murcia
      and Murcia Capital) in Spain. PARTICIPANTS: A total of 1424 healthy pregnant
      women with amenorrhea of <or=84 days who voluntarily decided to terminate their
      pregnancy participated in the study. METHODS: Women were randomly assigned to
      receive a single dose of 400 microg of misoprostol either sublingually or
      vaginally 1-3 h before aspiration. OUTCOME MEASURES: The outcome measures
      assessed were cervical dilation before surgery and surgical time needed for
      aspiration. The incidence of side effects, such as nausea, vomiting, diarrhea,
      fever/chills and paresthesia, was evaluated. RESULTS: The mean cervical dilation
      achieved was 6.8+/-0.8 and 6.7+/-0.9 mm for the sublingual and vaginal groups,
      respectively. The mean surgical time was 7.0+/-2.8 and 7.4+/-2.5 min for the
      sublingual and vaginal groups, respectively. Nausea, vomiting and diarrhea were
      more frequent in the sublingual group. CONCLUSIONS: Both regimens had equal
      efficacy; however, the sublingual route caused more side effects.

PMID- 16982236
TI  - Timing of steps and reasons for delays in obtaining abortions in the United
      States.
AB  - OBJECTIVE: We studied the steps in the process of obtaining abortions and women's
      reported delays in order to help understand difficulties in accessing abortion
      services. METHODS: In 2004, a structured survey was completed by 1209 abortion
      patients at 11 large providers, and in-depth interviews were conducted with 38
      women at four sites. RESULTS: The median time from the last menstrual period to
      suspecting pregnancy was 33 days; the median time from suspecting pregnancy to
      confirming the pregnancy was 4 days; the median time from confirming the
      pregnancy to deciding to have an abortion was 0 day; the median time from
      deciding to have an abortion to first attempting to obtain abortion services was
      2 days; and the median time from first attempting to obtain abortion services to
      obtaining the abortion was 7 days. Minors took a week longer to suspect pregnancy
      than adults did. Fifty-eight percent of women reported that they would have liked
      to have had the abortion earlier. The most common reasons for delay were that it
      took a long time to make arrangements (59%), to decide (39%) and to find out
      about the pregnancy (36%). Poor women were about twice as likely to be delayed by
      difficulties in making arrangements. CONCLUSIONS: Financial limitations and lack
      of knowledge about pregnancy may make it more difficult for some women to obtain
      early abortion.

PMID- 16982237
TI  - Efficacy of suppository analgesia in postabortion pain reduction.
AB  - PURPOSE: Termination of pregnancy is a painful procedure. Currently, there are no
      sufficient data regarding the best mode to reduce this pain. The aim of the study
      was to evaluate postabortion pain levels and to examine the analgesic effect of
      three different generic types of suppositories provided at the end of the
      surgical procedure prior to awakening from general anesthesia. METHOD: Two
      hundred seventeen women were randomly assigned to four groups: indomethacin (100
      mg), paracetamol (1000 mg), tramadol (100 mg), and control group with no
      suppository treatment. Pain levels were evaluated by VAS five times--15, 30, 60,
      90 and 120 min after abortion. The number of doses of rescue analgesia with
      dipyrone (1 g po) was recorded. RESULTS: There was a significant difference in
      pain levels between the four groups during the 2-h study (p<.05). Indomethacin
      always had the lowest VAS rank. Rescue analgesia was requested by 22/55 women in
      the control group, 10/55 in the tramadol group, 7/54 in the paracetamol group and
      5/53 in the indomethacin group (chi(2)=19.0, p<.0001). CONCLUSION: The
      application of a single suppository of an analgesic drug, especially
      indomethacin, is a simple, inexpensive and safe mode to reduce postabortion pain.

PMID- 16982238
TI  - Minor error in our paper which was recently published in Contraception.

PMID- 16982239
TI  - Re: improving contraceptive technology is not a zero-sum game.

PMID- 16982240
TI  - Contraception: an international perspective.

PMID- 16982242
TI  - Atypical presentation of serious pelvic inflammatory disease following
      mifepristone-induced medical abortion.

PMID- 16982246
TI  - Risk of nonfatal venous thromboembolism in women using a contraceptive
      transdermal patch and oral contraceptives containing norgestimate and 35 microg
      of ethinyl estradiol.

PMID- 16982247
TI  - Safety and efficacy of an extended-regimen oral contraception utilizing low-dose
      ethinyl estradiol.

PMID- 16982250
TI  - The otolaryngologist-ophthalmologist relationship: an historic perspective.
AB  - Otolaryngology and ophthalmology have a long and congenial professional
      relationship in the development of their mutual specialties over many years. In
      the early years they were one professional society, but later split into their
      separate specialties. Some problems involve both specialties because of the
      shared common anatomic areas. These problems include: orbital complications of
      sinusitis, management of exopthalmus, silent sinus syndrome, lacrimal apparatus
      problems, tumor and trauma problems, optic nerve decompression, and complications
      of endoscopic sinus surgery. Both specialties have their own expertise to
      contribute to these common problems. In many cases it is in the best interest of
      the patient if both specialties consult and contribute their knowledge,
      experience, and techniques in these cases. Otolaryngologists and opthalmologists
      continue their long and mutually respected professional relationship.

PMID- 16982251
TI  - Anatomy of the orbit, lacrimal apparatus, and lateral nasal wall.
AB  - Endoscopic approaches to the orbit take advantage of key anatomic relationships
      that arise from the fact that the sinonasal tract and orbit are contiguous
      structures separated by thin bone. For the most part, the orbit is surrounded by
      air-containing sinuses for much of the length of three of its four borders. Thus,
      a thorough understanding of both sinonasal and orbital anatomy is essential for
      safe and efficacious surgery in this complex region. The structural features of
      the lateral nasal wall and medial orbit are highlighted, and relevant aspects of
      orbital, lacrimal, and paranasal sinus anatomy are reviewed.

PMID- 16982252
TI  - Radiologic evaluation of lacrimal and orbital disease.
AB  - This article discusses the evaluation of specific lacrimal disorders and orbital
      trauma using CT, MRI, and other radiologic techniques.

PMID- 16982253
TI  - Traditional approaches to the orbit.
AB  - The selection of the surgical approach to the orbit depends on the indication for
      surgery and the location, size, and extent of the lesion. For the anterior half
      of the orbit, anterior orbitotomy provides adequate exposure. For the posterior
      half, more extensive procedures with osteotomy are necessary. This article
      details the external approaches to the orbit. The traditional approaches for
      orbital decompression for Grave's ophthalmopathy are also described.

PMID- 16982254
TI  - Office evaluation of lacrimal and orbital disease.
AB  - This article describes a stepwise system for evaluating the function of the
      lacrimal system. It discusses evaluation of the orbit with particular attention
      to thyroid eye disease and orbital fractures.

PMID- 16982255
TI  - Evaluation and management of Graves' orbitopathy.
AB  - Graves' orbitopathy, also known as Graves' ophthalmopathy or thyroid eye disease,
      is a potentially progressive but generally self-limited autoimmune process
      associated with hyperthyroidism. It is the most common cause of proptosis and the
      most common orbital inflammatory disorder in adults.

PMID- 16982256
TI  - Endoscopic orbital and optic nerve decompression.
AB  - The endoscopic transnasal approach is well suited for decompression of both the
      orbit and optic canal. High-resolution nasal endoscopes provide excellent
      visualization for bone removal along the orbital apex and skull base. Endoscopic
      orbital decompression has proved to be safe and effective for the treatment of
      patients with Graves' orbitopathy; however, the indications and outcomes for
      endoscopic decompression of the optic nerve remain controversial.

PMID- 16982257
TI  - Evaluation and management of congenital nasolacrimal duct obstruction.
AB  - Congenital nasolacrimal obstruction is a common disorder in infants that results
      in persistent tearing and may lead to infections, such as dacryocystitis, orbital
      cellulitis, and bacterial conjunctivitis. The true incidence of this disorder in
      healthy newborns remains controversial. The most frequently quoted number of 6%
      comes from a study of 200 consecutive live births in the 1940s in which
      nasolacrimal patency was assessed by the presence or absence of discharge on
      compression of the lacrimal sac. Estimates from other studies, which often use
      different criteria for diagnosis, vary considerably from 1.2% to 30%. The
      incidence of the disorder is higher in children who have craniofacial disorders
      and Down's syndrome. This article reviews the causes and treatment of congenital
      nasolacrimal obstruction.

PMID- 16982258
TI  - Acquired nasolacrimal duct obstruction.
AB  - Acquired nasolacrimal duct obstruction is a common problem. Although tearing is
      the usual complaint, the clinical presentation can range from a patient having no
      symptoms to one with a life-threatening infection. Despite many studies providing
      useful clues, the exact pathophysiology of the obstructive process is
      incompletely understood. The clinician must be able to accurately make the
      diagnosis, which is often a clinical one, because many treatments with excellent
      success are available.

PMID- 16982259
TI  - Endoscopic dacryocystorhinostomy and conjunctivodacryocystorhinostomy.
AB  - Intranasal approaches to the correction of lacrimal outflow obstruction initially
      were described more than 100 years ago, but they have gained renewed popularity
      with the recent development of the field of endoscopic sinus surgery. Endoscopic
      dacryocystorhinostomy (EDCR) surgery may be considered in many patients who have
      lacrimal outflow obstruction. It may be particularly advantageous in patients who
      have concomitant sinonasal disease, patients with a history of radiation therapy,
      pediatric patients, and in revision procedures. Advantages of the endoscopic
      technique include excellent visualization, the ability to evaluate the location
      and size of the rhinostomy site thoroughly, and the avoidance of a facial scar.
      Recent studies suggest that the success rates of EDCR are comparable to those
      achieved through traditional external dacryocystorhinostomy.

PMID- 16982260
TI  - Mechanical endonasal dacryocystorhinostomy with mucosal flaps.
AB  - Mechanical endonasal dacryocystorhinostomy (DCR) involves the creation of a large
      rhinostomy and the preservation of lacrimal and nasal mucosa. It replicates the
      main advantages of the external approach to DCR using minimally invasive
      techniques. A thorough knowledge of intranasal anatomy and the close
      collaboration of a multidisciplinary team are important when converting from the
      external to the endonasal approach.

PMID- 16982261
TI  - Endoscopic management of orbital abscesses.
AB  - Orbital complications of sinusitis have declined in the postantibiotic era.
      Nonetheless, the development of a subperiosteal or intraorbital abscess remains a
      serious condition that is best managed through a multidisciplinary approach.
      Surgical management is almost always indicated when orbital collections are
      present, and medical therapy plays a complimentary role. The endoscopic approach
      of draining a medial orbital collection offers significant advantages over the
      traditional external approach. The preoperative and intraoperative use of
      computer-aided technology may be a useful adjunct in the endoscopic management of
      orbital abscesses.

PMID- 16982262
TI  - Endoscopic orbital fracture repair.
AB  - Orbital fractures involving the middle or posterior third of the orbital floor
      are difficult to visualize with traditional surgical approaches. The authors
      describe their method of combining a transconjunctival incision with an endonasal
      endoscopic approach in the repair of orbital fractures. In their experience, this
      technique is especially useful in the treatment of posterior fractures or
      secondary repairs for residual enophthalmos. Besides better visualization,
      advantages include increased illumination; video projection for the rest of the
      surgical team and for documentation and recording; confirmation of correct
      implant placement; and, most importantly, precise and complete reduction of
      herniated orbital soft tissues.

PMID- 16982263
TI  - Endoscopic management of pediatric nasolacrimal anomalies.
AB  - Developmental anomalies of the nasolacrimal drainage system typically manifest
      early in childhood with epiphora and occasionally infection. Although the
      majority of cases of congenital nasolacrimal obstruction resolve spontaneously
      with conservative medical management, certain anomalies require operative
      intervention. Included in this latter group are dacryocystoceles or nasolacrimal
      duct cysts. The application of endoscopic sinus surgical techniques to children
      with persistent symptomatic nasolacrimal obstruction provides an alternative to
      external dacryocystorhinostomy that appears to be equally efficacious and
      concurrently allows for the potential correction of any predisposing intranasal
      pathology. Endonasal endoscopic dacryocystorhinostomy is best performed as a
      joint otolaryngologic-ophthalmologic procedure.

PMID- 16982264
TI  - Speed of injection influences efficacy of inferior alveolar nerve blocks: a
      double-blind randomized controlled trial in volunteers.
AB  - This randomized double-blind crossover trial investigated the efficacy and
      discomfort associated with slow (60 seconds) and rapid (15 seconds) inferior
      alveolar nerve blocks (IANB) using 2.0 ml of 2% lidocaine with 1:80,000
      epinephrine in securing mandibular first molar, premolar and lateral incisor pulp
      anesthesia in 38 healthy adult volunteers. Episodes of maximal stimulation (80
      microA) without sensation on electronic pulp testing were recorded. Injection
      discomfort was self-recorded by volunteers on 100 mm visual analogue scales. Data
      were analyzed by McNemar, Friedman, Wilcoxon Signed Ranks, and paired t tests.
      Slow IANB produced more episodes of no response to maximal pulp stimulation than
      rapid IANB in molars (220 episodes versus 159, p < 0.001), premolars (253
      episodes versus 216, p = 0.003) and lateral incisors (119 episodes versus 99, p =
      0.049). Slow IANB was more comfortable than rapid IANB (p = 0.021).

PMID- 16982265
TI  - Demographic characteristics of endodontic practice sites in the United States.
AB  - Few studies have addressed the demographic characteristics of dental practice
      sites including endodontic practice sites. This study investigated the
      demographic characteristics of endodontic practice sites in the United States.
      Demographic data and endodontic practices were organized by zip codes and
      analyzed using discriminant analysis. The demographic characteristics associated
      with zip codes that contained an endodontic practice were determined versus the
      characteristics of zip codes that did not contain an endodontic practice. The
      resulting model correctly classified 93.7% of the 30,171 zip code areas based
      upon the presence or absence of an endodontic practice. The variables most
      closely associated with a zip code containing an endodontic practice included:
      number of dental practices (nonendodontic), population size, percent of adult
      population with a college degree, size of employed population, projected
      population growth (2005 to 2010), percent of population over 64 years old, and
      median housing value.

PMID- 16982266
TI  - Survival rate of endodontically treated teeth with posts after prosthetic
      restoration.
AB  - The purpose of this retrospective clinical study was to evaluate the survival
      rate of teeth that were endodontically treated and restored with endodontic posts
      and prosthodontic restorations. A total of 864 teeth in 360 patients were
      included in the study. Dental records and radiographs of the patients were
      evaluated and four parameters were documented. The parameters were type of post,
      type of prosthodontic restoration, observation time, and, in cases of failure,
      failure mode. Statistical survival analyses were performed according to Kaplan
      Meier. The mean observation time was 22.5 +/- 14.9 months. The calculated
      survival rates of the abutments were statistically significant different for
      fixed partial dentures (FPDs) and for removable partial dentures (RPDs) with
      survival rates of 92.7% and 51.0% after 60 months, respectively. Most of the
      presumed factors influencing the survival rate of endodontically treated abutment
      teeth only affected the outcome in the RPD group. Teeth restored with post and
      cores present a high risk for failure when used as abutments for conical-double
      crown-retained RPDs.

PMID- 16982267
TI  - Complicated root canal morphology of mandibular first premolar in a Chinese
      population using the cross section method.
AB  - The purpose of this study was to assess the canal anatomy and morphology of
      mandibular first premolars in a Chinese population. Eighty-two extracted
      mandibular first premolars with intact roots were collected and stored in a
      glutaraldehyde solution. The teeth were embedded in clear resin and the root
      length was measured. The roots were resected perpendicular to the long axis at 3,
      6, 9, and 12 mm from the apex. The resected root surfaces were polished, rinsed,
      dried, and stained with methylene blue. Digital photographs of the cross
      sectional root surfaces were made at 24X. The incidence of multiple canals and
      varied morphology was determined by two independent examiners. The results
      indicated that 54% of the mandibular first premolars demonstrated a single canal.
      Twenty-two percent contained two canals and 18% percent had C-shaped
      configuration. The C-shaped root canal occurred predominantly in the 3 and 6 mm
      sections with one or two canals coronally. A unique finding was the
      circumferential canal (apical delta), which was characterized by a single canal
      splitting into 3 or 4 canals. The incidence of circumferential canal was 6% and
      occurred only in the apical 3 mm cross-sections. Identification of this unique
      apical canal configuration and the high incidence of multiple canals in
      mandibular first premolars may explain endodontic treatment failure in this tooth
      group.

PMID- 16982268
TI  - Molecular analysis of Filifactor alocis, Tannerella forsythia, and treponema
      denticola associated with primary endodontic infections and failed endodontic
      treatment.
AB  - The aim of this study was to investigate the presence of strict anaerobes such as
      Filifactor alocis, Tannerella forsythia, and Treponema denticola in primary and
      secondary root-infected canals with periapical lesions by molecular analysis and
      the association of these species with specific endodontic signs and symptoms.
      Microbial samples were taken from 100 root canals, 50 with necrotic pulp tissues
      (NPT, primary infection), and 50 with failed endodontic treatment (FET, secondary
      infection). DNA was extracted from the samples, which were analyzed for the
      presence of three endodontic pathogens using species-specific primers and PCR. F.
      alocis were isolated from 23 canals with NPT and 12 canals with FET; T. forsythia
      from 12 canals with NPT and three canals with FET; T. denticola from 19 canals
      with NPT and 12 canals with TEP. Suggested associations were found between
      primary infection and the presence of F. alocis and T. forsythia (both p < 0.05).
      In particular, associations were found between: pain and F. alocis; swelling and
      F. alocis; tenderness to percussion and T. forsythia; mobility and T. forsythia
      and T. denticola; wet canals and F. alocis, T. forsythia, and T. denticola;
      purulent exsudate and F. alocis, T. forsythia and T. denticola; abscess and F.
      alocis, T. forsythia, and T. denticola (all p < 0.05). The findings of this study
      indicated that F. alocis, T. forsythia, and T. denticola seem to be associated
      with endodontic signs and symptoms. Additionally, F. alocis and T. forsythia were
      detected more frequently in teeth with necrotic pulp than in teeth with failing
      endodontic treatment.

PMID- 16982269
TI  - Quantitative three-dimensional analysis of root canal curvature in maxillary
      first molars using micro-computed tomography.
AB  - In endodontic therapy, access and instrumentation are strongly affected by root
      canal curvature. However, the few studies that have actually measured curvature
      are mostly from two-dimensional radiographs. The purpose of this study was to
      measure the three-dimensional (3D) canal curvature in maxillary first molars
      using micro-computed tomography (microCT) and mathematical modeling. Extracted
      maxillary first molars (46) were scanned by microCT (502 image slices/tooth, 1024
      X 1024 pixels, voxel size of 19.5 x 19.5 x 39.0 microm) and their canals
      reconstructed by 3D modeling software. The intersection of major and minor axes
      in the canal space of each image slice were connected to create an imaginary
      central axis for each canal. The radius of curvature of the tangential circle was
      measured and inverted as a measure of curvature using custom-made mathematical
      modeling software. Root canal curvature was greatest in the apical third and
      least in the middle third for all canals. The greatest curvatures were in the
      mesiobuccal (MB) canal (0.76 +/- 0.48 mm(-1)) with abrupt curves, and the least
      curvatures were in the palatal (P) canal (0.38 +/- 0.34 mm(-1)) with a gradual
      curve. This study has measured the 3D curvature of root canals in maxillary first
      molars and reinforced the value of microCT with mathematical modeling.

PMID- 16982270
TI  - Coaggregation interactions between oral and endodontic Enterococcus faecalis and
      bacterial species isolated from persistent apical periodontitis.
AB  - Interactions between Enterococcus faecalis and other species found in root canal
      infections might be important for the development and persistence of periapical
      disease. The aim of this study was to investigate the coaggregation interactions
      between E. faecalis clinical isolates and species previously shown to survive and
      induce apical periodontitis in monkeys: Peptostreptococcus anaerobius, Prevotella
      oralis, Fusobacterium nucleatum, and Streptococcus anginosus. Intergeneric
      coaggregation assays were conducted in duplicate with observations scored
      immediately at 0 h, 1 h and 24 h after mixing of combinations of strains. All E.
      faecalis strains (n = 53) coaggregated with F. nucleatum; E. faecalis did not
      coaggregate with P. anaerobius or S. anginosus. One strain, E. faecalis E1,
      coaggregated with P. oralis, with aggregates visible at 1 h. Coaggregation
      interactions between E. faecalis and F. nucleatum observed in this study suggest
      a potential role for this combination in endodontic infections.

PMID- 16982271
TI  - TLR4 mediates LPS-induced VEGF expression in odontoblasts.
AB  - Lipopolysaccharide (LPS) from gram-negative bacteria cell walls such as
      Prevotella intermedia and Escherichia coli induce vascular endothelial growth
      factor (VEGF) expression in odontoblasts, but not in undifferentiated dental pulp
      cells. CD14 and TLR4 are responsible for LPS signaling in macrophages, but their
      expression levels and function in dental pulp cells are unknown. We showed here
      that murine odontoblast-like cells (MDPC-23) express CD14 and TLR4 by
      immunohistochemistry and flow cytometry. In contrast, undifferentiated dental
      pulp cells (OD-21) presented low or no expression of these two receptors. MDPC-23
      cells showed CD14 and TLR4 up-regulation upon exposure to LPS, as determined by
      real time PCR. Dominant negative murine TLR4 (DN-mTLR4) transfected MDPC-23 cells
      did not show upregulated VEGF expression in response to LPS stimulation. These
      results demonstrate that odontoblast-like cells express CD14 and TLR4, and that
      LPS-induced VEGF expression is mediated, at least in part, by TLR4 signaling.

PMID- 16982272
TI  - Apical leakage of root-end placed SuperEBA, MTA, and Geristore restorations in
      human teeth previously stored in 10% formalin.
AB  - The purpose of this study was to determine if storage of extracted teeth in 10%
      formalin affects microleakage of MTA, Geristore, or SuperEBA root-end fillings.
      There were 130 freshly extracted single-rooted teeth collected, immediately
      placed in phosphate buffered saline (PBS) and stored for less than 24 hours.
      Teeth were divided and either placed in 10% formalin for a 4-weeks immersion or
      immediately prepared. Preparation for all teeth consisted of canal
      instrumentation, obturation, apical resection, retrograde preparation, and
      placement of a root-end filling material. After 72 hours, the apical portions
      were immersed in India ink under vacuum pressure for 30 minutes, and then stored
      in ink for 1 week. Negative controls and positive controls performed as expected.
      In general, there was significantly less dye leakage of root-end restorations in
      teeth stored in 10% formalin when compared to the freshly extracted teeth (p <
      0.0001). No difference in dye leakage was observed between Geristore restorations
      placed in teeth stored in formalin as compared to fresh teeth (p = 0.892). Less
      dye leakage was noted in teeth restored with Geristore as compared to MTA and
      SuperEBA, regardless of storage medium (p < 0.0001). No difference was observed
      between MTA and SuperEBA root-end restorations (p = 0.157). The results of this
      study provide evidence that storage of teeth in 10% formalin over a 4-week period
      may significantly influence dye leakage as compared to leakage in freshly
      extracted teeth.

PMID- 16982273
TI  - Comparison of the shaping ability of RaCe and FlexMaster rotary nickel-titanium
      systems in simulated canals.
AB  - The aim of this study was to compare the shaping ability of RaCe and FlexMaster
      rotary nickel-titanium instruments in simulated canals. A total of 80 canals with
      four different shapes were prepared with either RaCe or FlexMaster instruments.
      Pre- and postoperative images of each canal were recorded and combined using
      image analysis software. The development of canal aberrations and transportation
      was assessed. There was a significant difference (p < 0.001) between the systems
      for time of preparation to apical size 30, .06 taper; FlexMaster instruments took
      on average 1.86 min and RaCe 1.66 min. One RaCe and two FlexMaster instruments
      fractured. No zips, elbows, or danger zones were created. One perforation and
      eight outer widenings were created using FlexMaster instruments; RaCe instruments
      created two outer widenings. No differences were found between the instruments
      for direction of transportation. RaCe and FlexMaster nickel-titanium instruments
      prepared canals rapidly with few aberrations.

PMID- 16982274
TI  - An in vitro comparison of the intraradicular dentin bond strength of Resilon and
      gutta-percha.
AB  - The purpose of this study was to compare the micropush-out bond strength of
      Resilon to that of gutta-percha. Extracted human anterior teeth were used for
      evaluation. The crowns were removed and the root canals were instrumented with
      Gates Glidden drills and 0.06 Profile rotary files. Instrumentation was performed
      with 5.25% sodium hypochlorite irrigation and a final rinse of 17% EDTA. The
      teeth were randomly divided into two groups. Gutta-percha group: obturation with
      gutta-percha and Kerr Pulp Canal Sealer EWT. Resilon group: obturation with
      Resilon points, Epiphany Primer, and Root Canal Sealant. The teeth were cut
      perpendicular to their long axis to obtain a series of 1.0 mm thick disks (n = 15
      per group). Micropush-out bond strengths to root canal dentin were measured. The
      results show that the mean bond strength to root canal dentin was significantly
      higher (p < 0.05) in the Resilon/Epiphany group as compared to the gutta
      percha/Kerr Pulp Canal Sealer EWT group.

PMID- 16982275
TI  - Effects of sodium hypochlorite and chlorhexidine solutions on Resilon (synthetic
      polymer based root canal filling material) cones: an atomic force microscopy
      study.
AB  - The aim of the present study is to evaluate the effects of 2% chlorhexidine and
      5.25% sodium hypochlorite on the surface properties of Resilon cones with the
      atomic force microscopy. The Resilon cones were immersed in disinfecting agents
      (5.25% sodium hypochlorite and 2% chlorhexidine) at 1 and 5 min time intervals.
      Atomic force microscopy was used to evaluate topographical deviations of Resilon
      cones. Root mean square (RMS) parameters for topographic amplitudes were
      calculated. The cones exhibited statistically significant low RMS values at 5-min
      immersion in sodium hypochlorite and chlorhexidine groups compared to the all
      other groups (p < 0.05). One-minute immersion did not show any significant
      deterioration on the Resilon surface (p > 0.05). In conclusion, sodium
      hypochlorite and chlorhexidine solutions used for disinfection significantly
      decreased (p < 0.05) the RMS values of Resilon cones at 5-min applications.

PMID- 16982276
TI  - Reduction in antimicrobial substantivity of MTAD after initial sodium
      hypochlorite irrigation.
AB  - Potential intrinsic tetracycline staining of intraradicular dentin has been
      observed when BioPure MTAD was employed as the final irrigant after initial
      rinsing with NaOCl. This study examined the effect of NaOCl-MTAD interaction on
      the antimicrobial substantivity of MTAD in dentin. Dentin cores previously
      irrigated with either MTAD, or in conjunction with 1.3% NaOCl as an initial
      irrigant were placed on blood agar plates inoculated with Escherichia faecalis at
      10(5) cfu/ml. Dentin cores irrigated with 1.3% NaOCl only, and autoclaved dentin
      disks were used as the respective positive and negative controls. After anaerobic
      incubation, the mean diameter of bacterial inhibition zones formed around the
      MTAD group was significantly larger than the NaOCl/MTAD group, which, in turn,
      was not significantly different from the NaOCl positive control. Oxidation of
      MTAD by NaOCl resulted in the partial loss of antimicrobial substantivity in a
      manner similar to the peroxidation of tetracycline by reactive oxygen species.

PMID- 16982277
TI  - An in vitro evaluation of the apical sealing ability of a new resin-based root
      canal obturation system.
AB  - The purpose of this study was to assess the apical sealing ability of the new
      resin-based Epiphany-Resilon root canal filling system, and to compare this with
      the sealing abilities of different pairings of AH plus, gutta-percha, Epiphany,
      and Resilon. Seventy extracted human single-rooted teeth were used. All teeth
      were instrumented using a set of ProTaper rotary instruments. The canal spaces
      were filled with different combinations of core and sealer using lateral
      condensation, as follows: group 1, AH Plus + gutta-percha; group 2, AH Plus +
      Resilon; group 3, Epiphany + Resilon; group 4, Epiphany + gutta-percha. Apical
      leakage quantity was measured with the computerized fluid filtration meter.
      Statistical analysis indicated that Epiphany gutta-percha combination had the
      least amount of microleakage than all the other groups; AH Plus gutta-percha
      combination proved to have second least amount of microleakage among the groups.
      AH Plus-Resilon combination demonstrated the greatest amount of microleakage.
      There were a significant difference between Epiphany gutta-percha and AH Plus
      Resilon combinations (p < 0.05). It was found that there were no significant
      differences between Epiphany-Resilon combination and all the other groups (p >
      0.05).

PMID- 16982278
TI  - Photodynamic therapy for endodontic disinfection.
AB  - The aims of this study were to investigate the effects of photodynamic therapy
      (PDT) on endodontic pathogens in planktonic phase as well as on Enterococcus
      faecalis biofilms in experimentally infected root canals of extracted teeth.
      Strains of microorganisms were sensitized with methylene blue (25 microg/ml) for
      5 minutes followed by exposure to red light of 665 nm with an energy fluence of
      30 J/cm2. Methylene blue fully eliminated all bacterial species with the
      exception of E. faecalis (53% killing). The same concentration of methylene blue
      in combination with red light (222 J/cm2) was able to eliminate 97% of E.
      faecalis biofilm bacteria in root canals using an optical fiber with multiple
      cylindrical diffusers that uniformly distributed light at 360 degrees. We
      conclude that PDT may be developed as an adjunctive procedure to kill residual
      bacteria in the root canal system after standard endodontic treatment.

PMID- 16982279
TI  - Effect of root canal treatments on quartz fiber posts bonding to root dentin.
AB  - The aim of this study was to evaluate the effect of irrigants and endodontic
      sealers on fiber post push-out strength in both fatigue cycling and no-cycling
      conditions. Fifty single-rooted human teeth received five endodontic treatments.
      The posts were cemented using a flowable composite and a three-steps adhesive.
      Five specimens from each group were subjected to 2 x 10(6) cycles of 37.5 N.
      There were 200 sections obtained for the push-out test. Fatigue cycled groups
      treated with an eugenol-containing sealer showed the lowest push-out strength (p
      < 0.001). No significant differences were found among no-cycled groups (p =
      0.665). The post-cement interface was found to be weaker than the cement-dentin
      one. However, fatigue cycles increased the occurrence of cement-dentin failures
      (p = 0.001). The eugenol-containing sealer reduced the bonding of fiber posts
      when mechanically cycled, thus the use of a resin-based sealer is advisable.

PMID- 16982280
TI  - Initial in vitro biological response to contemporary endodontic sealers.
AB  - The objective of this study was to evaluate the cytotoxicity of three endodontic
      sealers (AH Plus/Maillefer-Dentsply, Epiphany/Pentron, GuttaFlow, Coltene
      Whaledent). Materials were mixed according to the manufacturer instructions and
      packed into Teflon molds (10 x 1 mm). For cytotoxicity testing (MTT method), the
      specimens were placed in contact with cultured cells, then evaluated at two
      subsequent time points (24 or 72 h). In addition to testing the mixed materials,
      5 microl of primer liquid (GuttaFlow and Epiphany) and resin solvents (HEMA,
      ethanol, sterile water, or acetone) were added directly in culture for 24 and 72
      h. The results showed that most materials pose significant cytotoxic risks and
      that cytotoxicity generally increased with time. At 72 h, GuttaFlow became
      significantly less toxic than AH Plus, Epiphany sealer, and Resilon. The current
      results support the need to continue to develop better endodontic sealers that
      combine the excellent sealing and bonding properties of resins with acceptable
      biological properties for endodontic applications.

PMID- 16982281
TI  - The effectiveness of different acid irrigating solutions in root canal cleaning
      after hand and rotary instrumentation.
AB  - The goal of this study was to evaluate the cleaning ability of three acid
      irrigating solutions after hand and rotary instrumentation. Eighty human teeth
      were randomly divided in eight groups. Four groups were prepared with hand
      instrumentation and other four with ProTaper. The irrigating solutions were 15%
      citric acid plus 2.5% NaOCl; 15% EDTA plus 2.5% NaOCl; 5% orthophosphoric acid
      plus 2.5% NaOCl; and 2.5% NaOCl alone as control. Canal walls were observed with
      scanning electron microscopy, and photomicrographs were taken in apical, middle,
      and coronal thirds. A scoring system for debris and smear layer was used. Acid
      solutions with 2.5% NaOCl were effective in the elimination of smear layer or
      debris, and no significant differences were showed in smear layer removal between
      techniques. However, 2.5% NaOCl did not remove smear layer or debris, and no
      significant differences in debris were observed between manual and rotary
      techniques.

PMID- 16982282
TI  - Polymicrobial leakage of four root canal sealers at two different thicknesses.
AB  - The present study investigated the sealing ability of four root canal sealers at
      two different thicknesses. There were 82 maxillary incisors roots prepared with
      Gates Glidden drills up to size 6 and divided into four groups: Pulp Canal
      Sealer, EndoREZ, Sealapex, and AH Plus. Each group was divided in two subgroups
      and gutta-percha cylinders 1.5 or 1 mm wide were used, respectively. The roots
      were mounted in a bacterial leakage model and the system was checked daily during
      the following 12 wk. Data were analyzed by Log-Rank test and Student t-test. In
      the thin layer samples, the sealers demonstrated similar results while, in the
      thick layer samples, AH Plus revealed the best performance. Generally, greater
      sealer thickness influenced negatively the sealing ability of the root canal
      filling, except in AH Plus samples.

PMID- 16982283
TI  - Maxillary central incisor with two root canals: a case report.
AB  - The success of endodontic therapy requires a knowledge of the internal and
      external dental anatomy and its variations in presentation. The internal anatomy
      of the maxillary central incisor is well known and usually presents with one root
      and one radicular canal system. This case report describes an endodontic
      treatment of a maxillary central incisor with two roots and two canal systems,
      demonstrated by radiography and computerized tomography examinations.

PMID- 16982284
TI  - Cemental tear: a case report of a rare root fracture.
AB  - A 79-yr-old female presented to the clinic for endodontic evaluation of an
      unresolved periodontal defect. The patient's dental history included extraction
      of tooth #30 with subsequent placement of two dental implants. The patient
      presented with a localized periodontal defect on the distal of tooth #29.
      Radiographic evaluation revealed a thin radiopacity and associated radiolucency
      along the entire lateral aspect of tooth #29. Periodontal surgery and biopsy
      resulted in a diagnosis of cemental tear. Cemental tears have been rarely
      reported in the endodontic literature. Case reports of cemental tears have been
      associated with age, trauma, and traumatic occlusion. With the increasing age of
      the dental population and longer retention of teeth, clinicians should be aware
      of this rare entity.

PMID- 16982285
TI  - A review of the receptor-binding and pharmacokinetic properties of dopamine
      agonists.
AB  - BACKGROUND: Dopamine agonists (DAs), which can be categorized as ergot derived
      and non-ergot derived, are used in the treatment of Parkinson's disease.
      OBJECTIVES: This review describes the pharmacologic and pharmacokinetic
      properties of selected DAs and relates these characteristics to clinical
      outcomes, with an emphasis on adverse events. METHODS: Relevant articles were
      identified through a search of MEDLINE (to May 2006) using the terms dopamine
      agonists (or each individual drug name) and pbarmacokinetics, metabolism, drug
      drug interaction, interactions, CYP450, fibrosis, valvular heart disease, tremor,
      clinical trials, reviews, and meta-analyses. Abstracts from recent sessions of
      the International Congress of Parkinson's Disease and Movement Disorders were
      also examined. Clinical studies with <20 patients overall or <10 patients per
      treatment group in the final analysis were excluded. All DAs that were graded at
      least possibly useful with respect to at least 3 of 4 items connected to the
      treatment/prevention of motor symptoms/complications in the most recent evidence
      based medical review update were included. This resulted in a focus on the ergot
      derived DAs bromocriptine, cabergoline, and pergolide, and the non-ergot-derived
      DAs pramipexole and ropinirole. RESULTS: Bromocriptine, cabergoline, pergolide,
      and ropinirole, but not pramipexole, have the potential for drug-drug
      interactions mediated by the cytochrome P450 (CYP) enzyme system. The occurrence
      of dyskinesia may be linked to stimulation of the dopamine D(1) receptor, for
      which cabergoline and pergolide have a similar and relatively high affinity;
      bromocriptine, pramipexole, and ropinirole have been associated with a lower risk
      of dyskinesias. The valvular heart disease (VHD) and pulmonary and
      retroperitoneal fibrosis seen with long-term use appear to represent a class
      effect of the ergot-derived DAs that may be related to stimulation of serotonin 5
      HT(2B) (and possibly 5-HT(2A)) receptors. The incidence of valvular regurgitation
      was 31% to 47% with ergot-derived DAs, 10% with non-ergot-derived DAs, and 13%
      with controls. CONCLUSIONS: As reflected in the results of the clinical trials
      included in this review, dyskinesia associated with DA therapy may be linked to
      stimulation of the D(1) receptor. Fibrosis (including VHD) seemed to be a class
      effect of the ergot-derived DAs. Each of the DAs except pramipexole has the
      potential to interact with other drugs via the CYP enzyme system.

PMID- 16982286
TI  - Tigecycline: a glycylcycline antimicrobial agent.
AB  - BACKGROUND: Tigecycline, the first glycylcycline to be approved by the US Food
      and Drug Administration, is a structural analogue of minocycline that was
      designed to avoid tetracycline resistance mediated by ribosomal protection and
      drug efflux. It is indicated for the treatment of complicated skin and skin
      structure infections and complicated intra-abdominal infections and is available
      for intravenous administration only. OBJECTIVE: This article summarizes the in
      vitro and in vivo activities and pharmacologic and pharmacokinetic properties of
      tigecycline, and reviews its clinical efficacy and tolerability profile. METHODS:
      Relevant information was identified through a search of MEDLINE (1966-April
      2006), Iowa Drug Information Service (1966-April 2006), and International
      Pharmaceutical Abstracts (1970-April 2006) using the terms tigecycline, GAR-936,
      and glycylcycline. Also consulted were abstracts and posters from meetings of the
      Infectious Diseases Society of America and the Interscience Conference on
      Antimicrobial Agents and Chemotherapy (1999-2006) and documents provided for
      formulary consideration by the US manufacturer of tigecycline. RESULTS: Like the
      tetracyclines, tigecycline binds to the 30S subunit of bacterial ribosomes and
      inhibits protein synthesis by preventing the incorporation of amino acid residues
      into elongating peptide chains. In vitro, tigecycline exhibits activity against a
      wide range of clinically significant gram-positive and gram-negative bacteria,
      including multidrug-resistant strains (eg, oxacillin-resistant Staphylococcus
      aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase
      producing Enterobacteriaceae), and anaerobes (eg, Bacteroides spp). In
      pharmacokinetic studies in human adults, tigecycline had a large Vd (7-9 L/kg),
      was moderately bound to plasma protein (71%-89%), had an elimination t(1/2) of
      42.4 hours, and was eliminated primarily by biliary/fecal (59%) and renal (33%)
      excretion. Dose adjustment did not appear to be necessary based on age, sex,
      renal function, or mild to moderate hepatic impairment (Child-Pugh class A-B). In
      patients with severe hepatic impairment (Child-Pugh class C), the maintenance
      dose should be reduced by 50%. In 4 Phase III clinical trials in patients with
      complicated skin and skin-structure infections and complicated intra-abdominal
      infections, tigecycline was reported to be noninferior to its comparators
      (vancomycin + aztreonam in 2 studies and imipenem/cilastatin in 2 studies), with
      clinical cure rates among clinically evaluable patients of >80% (P < 0.001 for
      noninferiority). The most frequently reported (> or =5 %) adverse events with
      tigecycline were nausea (28.5%), vomiting (19.4%), diarrhea (11.6%), local IV
      site reaction (8.2%), infection (6.7%), fever (6.3%), abdominal pain (6.0%), and
      headache (5.6%). The recommended dosage of tigecycline is 100 mg IV given as a
      loading dose, followed by 50 mg IV g12h for 5 to 14 days. CONCLUSIONS: In
      clinical trials, tigecycline was effective for the treatment of complicated skin
      and skin-structure infections and complicated intra-abdominal infections. With
      the exception of gastrointestinal adverse events, tigecycline was generally well
      tolerated. With a broad spectrum of activity that includes multidrug-resistant
      gram-positive and gram-negative pathogens, tigecycline may be useful in the
      treatment of conditions caused by these pathogens.

PMID- 16982287
TI  - Comparative sensitivity of stopwatch methodology and conventional pain assessment
      measures for detecting early response to triptans in migraine: results of a
      randomized, open-label pilot study.
AB  - BACKGROUND: The standard measure of efficacy used in migraine trials is a 4-point
      patient-rated headache pain intensity (HPI) scale. However, it has been suggested
      that using a stopwatch to measure the time to meaningful pain relief can provide
      a more precise measurement of treatment response. OBJECTIVE: This study evaluated
      the sensitivity of a stopwatch method for detecting meaningful relief of headache
      pain and the correlation of this method with the HPI scale and a 5-point pain
      relief scale. METHODS: In this open-label, parallel-group pilot study, patients
      were randomized to receive oral eletriptan 40 mg, eletriptan 80 mg, or
      rizatriptan 10 mg for the treatment of a single acute migraine attack. The effect
      of study treatment on migraine pain was assessed immediately before dosing and at
      0.5, 1, 1.5, 2, 3, and 4 hours after dosing. At each time point, patients
      recorded the 3 types of pain assessment in a patient diary. HPI was rated using
      the standard 4-point International Headache Society pain intensity scale (from 0
      = no pain to 3 = severe pain). Pain relief was rated on a 5-point pain relief
      scale (from 4 = no relief to 0 = complete relief). The time to the onset of
      meaningful pain relief was measured using a stopwatch. At 4 hours after dosing,
      patients provided a global rating of the overall efficacy of study medication on
      a 5-point scale (from 0 = poor to 4 = excellent). RESULTS: Seventy-nine patients
      participated in the trial (78.5% female; mean [SD] age, 37.7 [9.8] years; 58.2%
      white). The median times to meaningful pain relief measured by stopwatch were 84,
      72, and 93 minutes for eletriptan 40 mg, eletriptan 80 mg, and rizatriptan 10 mg,
      respectively (log-rank P = 0.029, eletriptan 80 mg vs rizatriptan 10 mg). At 90
      minutes (approximating the median time to meaningful pain relief on the
      stopwatch), headache response rates using HPI scoring (mild to no pain) were 65%,
      68%, and 52% in the respective treatment groups, with no significant difference
      between groups. On the pain relief scale, the corresponding mean (SD) scores at
      90 minutes were 1.6 (1.2), 1.4 (1.3), and 2.0 (1.4) (P = NS). The pain relief
      defined response (> or = 75% pain relief) at 90 minutes did not differ
      significantly between the 3 treatment groups (62%, 56%, and 48%). Detection of
      early improvement (0.5 and 1 hour) was similar with the HPI and pain relief
      scales. CONCLUSION: The results of this open-label pilot study suggest the
      convergent validity of 3 pain-assessment methods in migraine, but indicate that
      the use of a stopwatch may be a more sensitive method for detecting between-group
      differences.

PMID- 16982288
TI  - Influence of age on flurbiprofen axetil requirements for preventing pain on
      injection of propofol in Japanese adult surgical patients: a prospective,
      randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study.
AB  - BACKGROUND: Pain on injection is a recognized adverse event (AE) of propofol
      administration for the induction of general anesthesia. Preceded by venous
      occlusion, flurbiprofen axetil, a prodrug of the NSAID flurbiprofen, has been
      associated with a reduction in pain induced by propofol injection. A review of
      the literature determined that no published data were available on the influence
      of age on the requirements for flurbiprofen axetil dose. OBJECTIVE: This study
      was undertaken to examine the influence of age on flurbiprofen axetil
      requirements for the treatment of propofol-induced pain on injection in Japanese
      adult surgical patients. METHODS: This prospective, randomized, double-blind,
      vehicle-controlled, parallel-group, dose-ranging study was conducted at the
      Department of Anesthesiology, Institute of Clinical Medicine, University of
      Tsukuba, Tsukuba, Japan. Young (age 20-40 years) and older (age 60-80 years)
      Japanese patients scheduled for various types of surgery (eg, cholecystectomy)
      were eligible. Patients were randomized to receive flurbiprofen axetil at 1 of 2
      doses (25 or 50 mg, regardless of body weight) or inactive vehicle (saline),
      preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and
      followed by the infusion of the first 25% of calculated propofol dose (0.5 mg/kg
      at room temperature, 23 degrees C) into the largest dorsal vein of the hand
      through a 20-G IV cannula (without local anesthesia), followed by the release of
      the occlusion and delivery of propofol 2 mg/kg. An investigator blinded to
      treatment questioned each patient about pain intensity during propofol injection
      which was assessed using a verbal rating scale: 0 = none; 1 = mild; 2 = moderate;
      and 3 = severe. The overall prevalence of pain was calculated in each group. AEs
      at the injection site (pain, edema, wheal, inflammation) were assessed by the
      study investigator for 24 hours after surgery using spontaneous reporting and
      patient interview. RESULTS: A total of 150 patients, 75 young adults (38 men, 37
      women; mean [SD] age, 31 [5] years; mean [SD] height, 163 [7] cm; mean [SD] body
      weight, 58 [9] kg) and 75 older adults (38 men, 37 women; mean [SD] age, 70 [6]
      years; mean [SD] height, 154 [8] cm; mean [SD] body weight, 53 [10] kg), were
      enrolled. Each treatment group comprised 25 patients. No differences in
      demographic characteristics were observed among the 3 study groups. In young
      patients, the overall prevalence of propofol-induced pain was significantly lower
      in patients who received flurbiprofen axetil 50 mg (12 [48%]) compared with that
      in patients who received flurbiprofen axetil 25 mg (20 [80%]) or vehicle (22
      [88%]) (P < 0.05 and P < 0.01, respectively). The median pain intensity score was
      significantly lower in patients who received flurbiprofen axetil 50 mg (0)
      compared with that in patients who received flurbiprofen axetil 25 mg (1) or
      vehicle (2) (P < 0.05 and P < 0.01, respectively). In older patients, the overall
      prevalences of pain on propofol injection were 9 (36%) in the flurbiprofen axetil
      50-mg group and 11 (44%) in the flurbiprofen axetil 25-mg group compared with 21
      (84%) in the vehicle group (both, P < 0.01). The median pain score was
      significantly lower in patients who received flurbiprofen 50 mg (0) or 25 mg (0)
      than in those who received vehicle (1) (both, P < 0.01). All treatments were well
      tolerated. CONCLUSIONS: In this small clinical trial in Japanese surgical
      patients undergoing general anesthesia, flurbiprofen axetil requirements for the
      reduction of pain during injection of propofol were found to be 50 mg in young
      adults (age 20-40 years) and 25 or 50 mg in older adults (age 60-80 years),
      regardless of weight, preceded by venous occlusion for 2 minutes.

PMID- 16982289
TI  - Hepatic disorders in patients treated with COX-2 selective inhibitors or
      nonselective NSAIDs: a case/noncase analysis of spontaneous reports.
AB  - BACKGROUND: Hepatic adverse events associated with the use of nonaspirin drugs
      and NSAIDs are uncommon, but the widespread use of these drugs may impact public
      health. OBJECTIVE: We conducted a case/noncase analysis of spontaneous reports to
      compare the hepatic safety profile of cyclooxygenase (COX)-2 selective inhibitors
      with that of nonselective NSAIDs. METHODS: This case/noncase analysis was
      conducted using the US Food and Drug Administration Freedom of Information
      (FDA/FOI) database (through quarter 1, 2003) and the World Health Organization
      Uppsala Monitoring Centre (WHO/UMC) database (through quarter 3, 2003). Council
      for International Organizations of Medical Sciences and WHO Adverse Reaction
      Terminology preferred terms were used to classify hepatic disorders with broad
      and specific case definitions. After reports involving established hepatotoxic
      drugs (bromfenac, nimesulide, sulindac) were excluded, the proportion of reports
      (PRs) of each case definition was calculated for each NSAID. Crude and adjusted
      reporting odds ratios (RORs) were used to compare the overall proportions of
      hepatic disorders and hepatic failure of celecoxib and rofecoxib versus
      nonselective NSAIDs. RESULTS: A total of 158,539 and 185,253 reports of NSAIDs
      were identified in the FDA/FOI and WHO/UMC databases and 25% and 16%,
      respectively, involved other hepatotoxic drugs. The PRs of hepatic disorders for
      all COX-2 selective inhibitors and non-selective NSAIDs were 3.0% in the FDA/FOI
      database and 2.7% in the WHO/UMC database. In the FDA/FOI and WHO/UMC databases,
      respectively, mmesulide (16.7% and 14.4%), bromfenac (12.0% and 20.7%),
      diclofenac (8.1% and 4.7%), and sulindac (6.1 % and 9.9%) were reported to be
      associated with higher proportions of overall hepatic disorders compared with
      those of other NSAIDs. Crude and adjusted RORs for the prevalences of overall
      hepatic disorders and hepatic failure with celecoxib and rofecoxib versus the
      other NSAIDs were <1 (indicating that the proportion was not higher than that of
      the comparator) in both databases. The interpretation of the results was
      unchanged when bromfenac, nimesulide, and sulindac were excluded from the
      analysis. CONCLUSIONS: In this case/noncase analysis, bromfenac, nimesulide,
      sulindac, and diclofenac had higher proportions of reports of hepatic disorders
      compared with those of other NSAIDs in the FDA/FOI and WHO/UMC databases. The
      analysis did not raise a safety concern for celecoxib or rofecoxib versus NSAIDs
      for overall hepatic disorders and hepatic failure.

PMID- 16982290
TI  - Clinically important drug-disease interactions and their prevalence in older
      adults.
AB  - BACKGROUND: Older adults may have decreased homeostatic reserve, have multiple
      chronic diseases, and take multiple medications. Therefore, they are at risk for
      adverse outcomes after receiving a drug that exacerbates a chronic disease.
      OBJECTIVES: The aims of this study were to compile a list of clinically important
      drug-disease interactions in older adults, obtain the consensus of a
      multidisciplinary panel of geriatric health care professionals on these
      interactions, and determine the prevalence of these interactions in a sample of
      outpatients. METHODS: This analysis included a 2-round modified Delphi survey and
      cross-sectional study. Possible drug-disease interactions in patients aged > or
      =65 years were identified through a search of the English-language literature
      indexed on MEDLINE and International Pharmaceutical Abstracts (1966-July 2004)
      using terms that included drug-disease interaction, medication errors, and
      inappropriate prescribing. Nine health care professionals with expertise in
      geriatrics (2 geriatricians, 7 geriatric clinical pharmacist specialists) were
      selected based on specialty training and continuing clinical work in geriatrics,
      academic appointments, and geographic location. The panel rated the importance of
      the potential drug-disease interactions using a 5-point Likert scale (from 1 =
      definitely not serious to 5 = definitely serious). Consensus on a drug-disease
      interaction was defined as a lower bound of the 95% CI > or =4.0. The prevalence
      of drug-disease interactions was determined by applying the consensus criteria to
      a convenience sample of frail older veterans at hospital discharge who were
      enrolled in a health services intervention trial. RESULTS: The panel reached
      consensus on 28 individual drug-disease interactions involving 14 diseases or
      conditions. Overall, 205 (15.3%) of the 1340 veterans in the sample had > or =1
      drug-disease interaction. The 2 most common drug-disease interactions were use of
      first-generation calcium channel blockers in patients with congestive heart
      failure and use of aspirin in patients with peptic ulcer disease (both, 3.7%).
      CONCLUSIONS: A survey of multidisciplinary geriatric health care professionals
      resulted in a concise consensus list of clinically important drug-disease
      interactions in older adults. Further research is needed to examine the impact of
      these drug-disease interactions on health outcomes and their applicability as
      national measures for the prevention of drug-related problems.

PMID- 16982291
TI  - Patterns of dosage changes with transdermal buprenorphine and transdermal
      fentanyl for the treatment of noncancer and cancer pain: a retrospective data
      analysis in Germany.
AB  - BACKGROUND: Previous studies have suggested that buprenorphine may have a low
      association with tolerance development compared with other strong opioids. In a
      previous study by our group, mean cohort and intraindividual dosage increases
      over an entire course of treatment and on a per-day basis were significantly
      lower with transdermal (TD) buprenorphine than with TD fentanyl. However, no
      information concerning the relationship between qualitative and quantitative dose
      changes is available. OBJECTIVE: The aim of this study was to compare TD
      buprenorphine and TD fentanyl with respect to dosage increases, dosage stability,
      and the nature of dosage changes. METHODS: This retrospective analysis used data
      from the IMS Disease Analyzer-Mediplus database, which contains patient-related
      data documented by 400 medical practices in Germany. Data from patients with
      noncancer or cancer pain treated with TD buprenorphine or TD fentanyl for at
      least 3 months between May 2002 and April 2005 were analyzed. Daily dosages were
      directly determined from the prescribed patch strength, taking into account the
      possibility of multiple patches applied simultaneously. To determine dosage
      stability, patients were classified based on the type of dosage change (stable,
      increase, alternating, or decrease) of the prescribed dosages. From the
      prescribed daily dosages, mean percentage increases were calculated on a per
      patient basis for the entire treatment period and per day, and these were
      assessed in relation to the type of dosage change. RESULTS: In total, 631
      patients with noncancer pain and 605 patients with cancer pain were included in
      the analysis (782 women, 454 men; mean age, 76.3 years [range, 29-100 years]).
      Treatment indications included osteoarthritis, low back pain, osteoporosis
      (noncancer groups), and neoplasm (cancer groups). Patients had similar analgesic
      premedication requirements based on steps 1 to 3 of the World Health Organization
      analgesic ladder. Comedication requirements for breakthrough pain were also
      similar between the TD buprenorphine and TD fentanyl groups. The mean percentage
      increases per day were 0.10% (TD buprenorphine) and 0.25% (TD fentanyl) in the
      noncancer groups and 0.19% (TD buprenorphine) and 0.47% (TD fentanyl) in the
      cancer groups (both, P < 0.05). A significantly larger proportion of patients
      receiving TD buprenorphine had stable dosages over the entire treatment period
      compared with patients receiving TD fentanyl (noncancer groups: 56.9% vs 41.6%;
      cancer groups: 50.0% vs 26.2% [both, P < 0.05]). Compared with TD buprenorphine,
      the proportion of patients with alternating dosage changes was significantly
      greater in patients receiving TD fentanyl (noncancer groups: 22.7% vs 13.1%;
      cancer groups: 30.6% vs 11.8% [both, P < 0.05]). CONCLUSIONS: In this
      retrospective data analysis, compared with TD buprenorphine, the increase in mean
      daily dosage was significantly greater in patients treated with TD fentanyl.
      Also, compared with TD buprenorphine, alternating dosage changes were seen in a
      significantly greater proportion of patients receiving TD fentanyl. On the other
      hand, a significantly greater proportion of patients treated with TD
      buprenorphine had stable dosages over their entire treatment periods.

PMID- 16982292
TI  - Effectiveness and tolerability of prolonged linezolid treatment for chronic
      osteomyelitis: a retrospective study.
AB  - BACKGROUND: Linezolid is an oxazolidinone agent which is apparently well designed
      for treating chronic osteomyelitis, but data on effectiveness and tolerability as
      prolonged therapy is currently lacking. OBJECTIVE: The purpose of this study was
      to assess the effectiveness and tolerability of linezolid in the treatment of
      chronic osteomyelitis. METHODS: The charts of hospitalized patients who had been
      treated with linezolid for >4 weeks because of chronic osteomyelitis and were
      followed up for > or =12 months after the end of treatment were retrospectively
      reviewed for clinical outcome and tolerability. Cure was defined as the absence
      of clinical, biological, or radiological evidence of infection throughout the
      posttreatment follow-up. Linezolid tolerability was assessed on the basis of
      hematologic properties during treatment. RESULTS: Of the 66 patients included,
      all were white (mean [SD] age, 67.7 [18.1] years; 41 men and 25 women; mean [SD]
      weight, 80.7 [18.6] kg). Thirty-seven (56.1%) patients had infection due to
      implants including 27 prosthetic joints. Pathogens were predominantly methicillin
      resistant staphylococci (49/72 strains, 68.1 %). Every patient was administered N
      linezolid (600 mg BID) treatment for 6 to 8 days as inpatients, and then, as
      outpatients, they were switched to PO treatment. Fifty (75.8%) patients received
      a combination of linezolid and other antimicrobial agents, including rifampin (32
      [48.5%]). Surgery was performed in 52 (78.8%) patients. The median hospital stay
      was 14 days (mean [SD], 19 [11.4] days [range, 7-70 days] ). The median duration
      of treatment was 13 weeks (mean [SD], 14.3 [8.2] weeks [range, 5-36 weeks]). At
      the end of treatment, 56 (84.8%) patients were cured, and during the post
      treatment follow-up (median duration, 15 months [range, 12-36 months]), 4
      relapses occurred, resulting in an overall successful cure for 52 (78.8%)
      patients. Reversible anemia was reported in 21 patients (31.8%), of whom 16
      (24.2%) required blood transfusions. Median time from treatment initiation to
      anemia onset was 7.3 weeks (range, 4-12 weeks). Peripheral neuropathy was
      reported in 6 (9.1%) patients, of whom 4 remained symptomatic for up to 24 months
      after linezolid discontinuation. Other reported adverse events included nausea (6
      [9.1%]), diarrhea (1 [1.5%]), and headache (2 [3.0%]), although none of these
      patients discontinued treatment. CONCLUSIONS: In this retrospective chart review,
      treatment with linezolid as monotherapy or in combination with antimicrobials
      and/or surgery was associated with cure of chronic osteomyelitis in 84.8% of
      subjects at 12 weeks after the end of treatment and 78.8% at follow-up. Adverse
      events were reported in 51.5% of subjects, and 34.8% of subjects discontinued the
      study because of adverse events. The potential for severe complications justifies
      close monitoring of these patients.

PMID- 16982293
TI  - A post hoc subgroup analysis of meropenem versus imipenem/cilastatin in a
      multicenter, double-blind, randomized study of complicated skin and skin
      structure infections in patients with diabetes mellitus.
AB  - BACKGROUND: In a multicenter, international, double-blind, randomized clinical
      trial involving hospitalized patients with complicated skin and skin-structure
      infections (cSSSIs), meropenem and imipenem/cilastatin (both administered 500 mg
      intravenously every 8 hours) were not significantly different in their efficacy
      and safety profiles. OBJECTIVE: The objective of the post hoc subgroup analysis
      discussed in the current article was to report the efficacy and tolerability of
      meropenem and imipenem/cilastatin for the treatment of cSSSIs in patients with or
      without underlying diabetes mellitus (DM). METHODS: Hospitalized patients aged >
      or =13 years with evidence of cSSSIs were eligible for inclusion. Patients were
      randomized to receive meropenem or imipenem/cilastatin, each 500 mg intravenously
      every 8 hours, for at least 3 days and up to a maximum of 14 days. Patients were
      analyzed according to the presence or absence of DM and by the pathogen(s)
      isolated from wound cultures at baseline, end of N treatment, and test-of-cure
      visits. The primary efficacy end point was clinical outcome at the posttreatment
      follow-up (test-of-cure) visit in the clinically evaluable and modified intent-to
      treat (intent-to-treat [ITT] subjects who met all eligibility criteria)
      populations; this was defined as 7 to 14 days after final administration of
      antibiotics. The secondary efficacy end points included clinical response at the
      test-of-cure visit in the ITT population (ie, those who received >1 dose of study
      drug) and at the end of N treatment visit in the clinically evaluable and fully
      evaluable populations. At baseline, the end of N treatment, and the test-of-cure
      visits, specimens were obtained from the most extensive site of skin and skin
      structure infection and were cultured for bacteria. Adverse events were monitored
      daily during treatment and for 30 days after the completion of all antibiotic
      treatment. RESULTS: Of the 1076 patients enrolled in the original study, 398 had
      DM. The mean ages of patients with and without DM were 55 and 45 years,
      respectively; 17.3% of patients with DM and 6.1% of patients without DM had
      impaired renal function at study entry. Complex abscess was the most common
      infection diagnosis in both groups (patients with DM, 30.0%; patients without DM,
      48.8%). The other top infections per group (patients with and without DM,
      respectively) were as follows: cellulitis, 24.6% and 12.4%; and ischemic/diabetic
      ulcers, 20.9% and 1.9%. Gram-negative aerobic and anaerobic pathogens accounted
      for >40% of bacterial isolates from both groups, with polymicrobial infections
      reported in 44.2% of patients with DM and 34.0% of patients without DM. In the
      clinically evaluable population, the satisfactory clinical response rate was
      85.6% for patients with DM receiving meropenem and 72.4% for those receiving
      imipenem/cilastatin; for patients without DM, those rates were 86.6% and 89.0%,
      respectively. Meropenem and imipenem/cilastatin were generally well tolerated.
      Reported adverse events were similar between groups. CONCLUSION: This subgroup
      analysis found that 500 mg every 8 hours intravenously of meropenem or
      imipenem/cilastatin appeared efficacious and well tolerated for the treatment of
      cSSSIs among these patients with and without DM.

PMID- 16982294
TI  - Levofloxacin 750 mg QD for five days versus amoxicillin/clavulanate 875 mg/125 mg
      BID for ten days for treatment of acute bacterial exacerbation of chronic
      bronchitis: a post hoc analysis of data from severely ill patients.
AB  - This post hoc analysis of data from a previous randomized, blinded, multicenter,
      parallel, noninferiority study assessed the bacterial etiology, symptom
      resolution, and tolerability of severe acute bacterial exacerbation of chronic
      bronchitis (ABECB) patients treated with either levofloxacin 750 mg QD for 5 days
      or amoxicillin/clavulanate 875 mg/125 mg BID for 10 days. Severe ABECB was
      defined as ABECB and forced expiratory volume in 1 second (FEV(1)) <50% of the
      predicted value, or (FEV(1)) of 50% to 65% of the predicted value plus
      comorbidities, or > or =4 exacerbations per year. A total of 369 patients were
      included in the intent-to-treat (ITT) population (187 treated with levofloxacin
      and 182 treated with amoxicillin/clavulanate), and 175 patients were
      microbiologically assessable (MA) (86 treated with levofloxacin and 89 treated
      with amoxicillin/clavulanate). In the ITT population, the mean age was 58.7
      years, 49.1 % were male, and 48.2% were current smokers. At the on-treatment
      visit, a significantly higher proportion of MA patients in the levofloxacin group
      resolved purulent sputum production (57.5% vs 35.6%; P < 0.006), sputum
      production (65.4% vs 45.3%; P < 0.013), and cough (60.0% vs 44.0%; P < 0.045),
      compared with the amoxicillin/clavulanate group. However, no significant between
      group differences were observed at posttreatment. A total of 341 pathogens were
      isolated, of which 143 (41.9%) were traditional ABECB flora, 181 (53.1%) were
      other gram-negative organisms, and 17 (5.0%) were gram-positive organisms.
      Overall susceptibility of the pathogens was 97.1% for levofloxacin and 90.6% for
      amoxicillin/clavulanate (P < 0.001). The prevalence of treatment-emergent adverse
      events was 42.1 % in patients who received levofloxacin and 48.6 % in those who
      received amoxicillin/clavulanate (95% CI,-4.0 to 17.0).

PMID- 16982295
TI  - The reference case ten years later: has comparing cost-effectiveness analyses
      improved?

PMID- 16982297
TI  - Comparison of medication adherence and associated health care costs after
      introduction of pioglitazone treatment in African Americans versus all other
      races in patients with type 2 diabetes mellitus: a retrospective data analysis.
AB  - OBJECTIVE: The aim of this study was to compare treatment adherence and health
      care costs in African Americans versus all other races (All Others) in patients
      with type 2 diabetes mellitus starting treatment with pioglitazone. METHODS: In
      this retrospective cohort study, the North Carolina Medicaid database was used
      (query dates: July 1, 2000, to June 30, 2003). Using at least 1 code from the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      for type 2 diabetes (250.xx) and 1 National Drug Code for antidiabetic
      medication, we identified a cohort of male and female patients aged > or =18
      years with type 2 diabetes who maintained continuous Medicaid eligibility for the
      entire 36-month follow-up period. Race was categorized as African American and
      All Others (white, Asian, Native American, Pacific Islander, other) based on self
      reported data collected at the time of Medicaid enrollment. Medication adherence
      was expressed as medication possession ratio (calculated as the number of days of
      antidiabetic prescription supply dispensed [eg, a 30-day supply] divided by the
      number of days between the first and last dispensation). Reimbursements made by
      Medicaid were used to calculate diabetes-related and total health care costs,
      which included medical and dental care, including costs for regular checkups,
      office visits, home health care, inpatient and outpatient care, long-term care
      facility care, and prescription drugs. To compare the differences in medication
      adherence and annual total and diabetes-related health care costs between African
      Americans and All Others, multivariate regression analysis was performed using
      only data from the year after (year 2) the year in which pioglitazone treatment
      was started (year 1). RESULTS: Among the 1073 patients treated with pioglitazone
      (26.1% men; mean [SD] age, 49.5 [10.6] years; 50.2% African American; mean [SD]
      total health care costs in year 1, US $7906 [$12,256]; year 2, $9546 [$14,861]),
      African Americans had significantly higher adherence (62%) to pioglitazone
      treatment compared with All Others (57%) (P < 0.05) on unadjusted analysis.
      However, no significant differences in rates of adherence to the medication were
      found between African Americans and All Others on multivariate regression
      analysis. African American race was not found to be an independent predictor of
      increased or decreased annual total health care costs in this population.
      Significant reductions in total health care costs (2% for every 10% increase in
      adherence; P < 0.001) and diabetes-related costs (4% for every 10% increase in
      adherence; P < 0.01) with increased adherence were found. CONCLUSIONS: On
      multivariate analysis, this study found no significant differences in treatment
      adherence between African Americans versus all other races in this population of
      diabetic patients enrolled in a Medicaid program (query dates: July 1, 2000, to
      June 30, 2003). A higher adherence rate was associated with significantly lower
      diabetes-related and total health care costs in this population.

PMID- 16982296
TI  - Cost-effectiveness analysis of linezolid compared with vancomycin for the
      treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus
      aureus.
AB  - OBJECTIVE: This study compared the cost-effectiveness of linezolid and vancomycin
      in the treatment of patients with nosocomial pneumonia (NP) caused by methicillin
      resistant Staphylococcus aureus (MRSA). METHODS: A retrospective decision
      analytic model was applied to pooled data from 2 prospective, randomized,
      controlled, double-blind studies, and claims data from a large health plan (3.3
      million members) located in the Mid-Atlantic region. Using hospital claims for
      patients in the health plan with suspected NP, we then determined their daily
      billed (submitted) hospital charges for 4 mutually exclusive potential health
      outcomes of linezolid or vancomycin treatment: survival with bacteremia, survival
      without bacteremia, nonsurvival with bacteremia, and nonsurvival without
      bacteremia. To generate the expected total daily billed hospital charge for each
      drug-treatment group, we weighted the determined daily billed hospital charges by
      the probabilities of each outcome developing in each treatment arm, as derived
      from the clinical-trial data. Drug acquisition costs were then incorporated, and
      the difference in expected total costs relative to the difference in rates of
      survival between the linezolid and vancomycin arms was used to calculate the
      incremental cost-effectiveness ratio (ICER) for linezolid. RESULTS: Costs were
      higher for nonsurviving patients compared with surviving patients. Estimated
      median daily billed treatment charges were $2888 for linezolid and $2993 for
      vancomycin. Based on Monte Carlo simulations, the respective 95% CIs were $2671
      to $3106 and $2615 to $3372. Using mean treatment durations of 11.3 and 10.7
      days, respectively, we obtained expected total hospitalization charges of $32,636
      for linezolid treatment (95% CI, $30,182-$35,098), compared with $32,024 for
      vancomycin treatment (95% CI, $27,978-$36,078). The ICER for linezolid per life
      saved was $3600. CONCLUSIONS: The higher acquisition cost of linezolid was almost
      completely offset by improved survival and a reduction in health care costs
      associated with improved survival. As a result, linezolid was almost cost-neutral
      compared with vancomycin in the treatment of NP caused by MRSA.

PMID- 16982299
TI  - A cross-national study of prescription nonadherence due to cost: data from the
      Joint Canada-United States Survey of Health.
AB  - BACKGROUND: In Canada and the United States, patients who have difficulty paying
      for prescribed medications are less likely to obtain them and may experience
      increased risks for morbidity and mortality and/or increased health care costs
      due to nonadherence. As prescription drug costs have risen, the ability to pay
      for medications has emerged as a critical public health issue. OBJECTIVES: The
      objectives of this study were to estimate the rates of cost-associated
      nonadherence in Canada and the United States, and to identify factors that
      predict cost-associated nonadherence in both countries. METHODS: This original
      analysis used data from the 2002/2003 Joint Canada-US Survey of Health, a
      household phone survey jointly conducted by Statistics Canada (Ottawa, Ontario,
      Canada) and the US National Center for Health Statistics (Hyattsville, Maryland).
      The sample included 3505 adults in Canada and 5183 adults in the United States.
      Weighted group comparisons and logistic regression analyses were used to identify
      population factors predictive of cost-associated prescription nonadherence.
      RESULTS: Residents of Canada were much less likely than residents of the United
      States to report cost-associated nonadherence (5.1% vs 9.9%; P < 0.001).
      Americans without health insurance (28.2%) and Americans and Canadians without
      prescription-drug coverage (16.2%) were significantly more likely than those with
      insurance (6.2%) to report cost-associated nonadherence (P < 0.001). In addition
      to country of residence and insurance coverage, significant risk factors
      predictive of nonadherence were young age, poor health, chronic pain, and low
      household income. CONCLUSIONS: The results of this analysis suggest that people
      with low incomes and inadequate insurance, as well as those with poor health
      and/or chronic symptoms, are more likely to report failing to fill a prescription
      due to cost. The overall rate of cost-associated nonadherence was significantly
      higher in the United States than in Canada, even when other person-level factors
      were controlled for, including health insurance and prescription-drug coverage.

PMID- 16982298
TI  - Case-control study of the relationship between MRSA bacteremia with a vancomycin
      MIC of 2 microg/mL and risk factors, costs, and outcomes in inpatients undergoing
      hemodialysis.
AB  - BACKGROUND: An increased prevalence of bacteremia caused by methicillin-resistant
      Staphylococcus aureus (MRSA) with a vancomycin hydrochloride MIC of 2 microg/mL
      was noted in a population of inpatients undergoing hemodialysis at Baptist
      Memorial Health Care, Memphis, Tennessee. OBJECTIVES: The aims of this study were
      to determine risk factors for infection with MRSA and to assess the differences
      in clinical and economic outcomes in patients undergoing hemodialysis with MRSA
      bacteremia with vancomycin MIC 2 microg/mL versus those with MRSA bacteremia with
      vancomycin MIC < or =0.5 microg/mL and uninfected controls. METHODS: This
      retrospective case-control study was conducted at Baptist Memorial Health Care.
      The study population (inpatients undergoing hemodialysis for MRSA bacteremia with
      vancomycin MIC 2 microg/mL [high-MIC group], MIC < or = 0.5 microg/mL [low-MIC
      group], and uninfected controls) was identified. Risk factors and clinical and
      economic outcomes (costs of hospitalization, nursing, and pharmacy) were
      determined and compared using univariate and multivariate statistics. RESULTS:
      Fifty patients with MRSA bacteremia undergoing hemodialysis were identified
      during the study period (high-MIC group, 17 [11 women, 6 men; mean (SD) age, 60
      (17) years]; low-MIC group, 33 [23 women, 10 men; mean (SD) age, 62 (14) years])
      and matched with 100 uninfected controls (57 men, 43 women; mean [SD] age, 63
      [15] years). Risk factors for MRSA bacteremia found to be associated with high
      MIC included female sex, higher body mass index (1-point increments), recent
      surgery, and a history of cardiovascular disease (P < 0.05, P < 0.046, P = 0.04,
      and P = 0.028, respectively) (multivariate analysis). In the outcomes analysis,
      mortality was significantly higher in the high-MIC group compared with those in
      the low-MIC and control groups (35% vs 24% and 15%, respectively; P = 0.022).
      Total mean (SD) hospitalization costs were significantly higher in the high-MIC
      group compared with those in the low-MIC group and controls (US $47,624 [$80,534]
      vs $26,792 [$25,167] and $13,185 [$15,568], respectively; P < 0.001). Nursing
      costs were almost 6-fold higher in both infected groups compared with those in
      controls. Pharmacy costs in the low- and high-MIC groups were 3- to 6-fold
      higher, respectively, compared with those in controls. CONCLUSIONS: Surgery
      within the previous 6 months and intensive care unit admission were identified as
      significant risk factors for patients with MRSA bacteremia with a vancomycin MIC
      2 microg/mL undergoing hemodialysis. These patients experienced a longer mean
      hospital length of stay and increased hospital costs compared with patients with
      MRSA bacteremia with a vancomycin MIC < or =0.5 microg/mL and uninfected
      controls.

PMID- 16982300
TI  - Application of concentration ratios to analyze the phenomenon of "next-door"
      pharmacy in Taiwan.
AB  - BACKGROUND: In Taiwan, a policy of separation of prescribing and dispensing
      practices of practitioners at Western medical and dental clinics was implemented
      on an incremental basis in 1997. The purpose of this policy was to promote
      pharmacists' autonomy and increase the transparency and safety of prescribing
      medications. To avoid profit loss from no longer being able to dispense
      prescription medications, some clinics opened pharmacies located under the same
      roof as the clinic ("next-door" pharmacies) or hired an on-site pharmacist. This
      practice might compromise pharmacists' professional autonomy and patients'
      benefit in pharmaceutical care. OBJECTIVE: The aim of the current study was to
      clarify the relationship between practicing pharmacies and clinics that resulted
      from contracts between pharmacies and the Bureau of National Health Insurance
      from 1996 to 2004. METHODS: The National Health Research Institutes database in
      Taiwan supplied the complete claims data sets of practicing pharmacies from 1997
      to 2004. The prescribing source of every dispensed prescription was used to
      calculate the 1-firm concentration ratio (CR-1) (ie, the proportion of
      prescriptions issued by the largest prescribing clinic/hospital in the total
      number of dispensed prescriptions of a pharmacy in each year). Similar processing
      was applied to the clinics. We identified each clinic's largest cooperating
      pharmacy and compared their CR-1s. Pharmacies that dispensed >900
      prescriptions/mo during the study period were considered thriving. Pharmacies
      with a CR-1 > or =0.99 and whose largest cooperating clinic had a CR-1 > or =0.99
      were considered to have a close business relationship, possibly indicating a next
      door pharmacy. RESULTS: The total number of prescriptions dispensed at all
      pharmacies in the database grew from 226,901 in 1996 to 59,785,039 in 2004, and
      the number of pharmacies, from 481 to 3529. An increasing number of pharmacies
      had a higher CR-1 after 1999. We found that most prescriptions could be dispensed
      at only 1 pharmacy during the study period. In 2004, 1429 clinics had >900
      prescriptions/mo dispensed externally and a CR-1 > or =0.99. They had released
      75.8% of all prescriptions to be dispensed at practicing pharmacies; 811 of these
      clinics had a cooperating pharmacy with a CR-1 > or =0.99. CONCLUSIONS: In this
      data analysis in Taiwan, most prescriptions from practitioners at Western medical
      and dental clinics could be dispensed at only 1 pharmacy during the study period,
      suggesting that pharmacists' professional autonomy and the patients' benefit in
      pharmaceutical care might be compromised in Taiwan.

PMID- 16982301
TI  - The decision-making process of US Food and Drug Administration advisory
      committees on switches from prescription to over-the-counter status: a
      comparative case study.
AB  - BACKGROUND: The US Food and Drug Administration (FDA) and FDA advisory committees
      have been under increasing scrutiny as a result of media attention to safety
      concerns. OBJECTIVE: This article compares the decision-making process of the
      FDA's Nonprescription Drugs Advisory Committee (NDAC) in 3 cases of a proposed
      switch from prescription to over-the-counter (OTC) status involving a nicotine
      replacement therapy product, 2 statins, and an emergency oral contraceptive.
      METHODS: This comparative case study reviewed written transcripts and slides from
      4 NDAC committee meetings and a digital video disc recording of a later meeting
      held to reconsider one of the proposed switches. The focus was on the committee's
      discussion and deliberation processes. Content analysis and iterative coding were
      used to assess the level of participation by committee members and the extent to
      which committee discussion adhered to both the key draft list questions provided
      by the FDA and the published DeLap criteria for switches from prescription to OTC
      status. Other major themes and discussion topics were identified, and the voting
      process was analyzed. RESULTS: In the absence of clearly defined meeting
      procedures, the advisory committees developed their own procedural standards.
      There were major differences between meetings in terms of the extent of
      discussion of the key draft list questions and adherence to the DeLap principles,
      discussion of other themes and topics, and voting methods. In each case, at least
      1 major topic of discussion was not directly related to safety, efficacy, or self
      use. Additional identified themes were the public health significance of a switch
      to OTC status, costs, and access. CONCLUSIONS: Variability in processes created
      discrepancies in the decision-making criteria used by the NDAC committees. There
      is a need to establish structured procedures to achieve an optimal level of
      uniformity and transparency in advisory committee processes.

PMID- 16982303
TI  - Long-term postoperative bleeding after dentoalveolar surgery in the pretransplant
      liver failure patient.
AB  - PURPOSE: A retrospective review of a protocol-driven single institutional
      experience for treatment of pretransplant liver failure patients requiring
      dentoalveolar procedures for transplant clearance. MATERIALS AND METHODS: Between
      January 2003 and June 2005, 30 liver failure patients requiring pretransplant
      dentoalveolar surgery at the University of Michigan Hospital were treated in the
      Department of Oral and Maxillofacial Surgery/Hospital Dentistry undergoing 35
      total procedures. These patients were stratified preoperatively into 3 different
      "risk" groups (minimal, moderate, high) based on number and complexity of teeth
      to be extracted as well as any planned adjunctive preprosthetic procedures.
      RESULTS: Analysis of variance (ANOVA) comparison of groups was conducted, as well
      as logistic regression analysis and 2-tailed Pearson correlation using chi2 and
      the Fisher exact test. The only statistically significant (P < .05) predictors of
      long-term postoperative bleeding were surgeon-defined "risk," the number of
      simple extractions, and quadrants of alveoplasty. Additional postoperative
      correlations were found between long-term bleeding and the need for hospital
      admission as well as the use of blood products for treatment. Model for end-stage
      liver disease (MELD), preoperative prothombin time (PT), preoperative partial
      thromboplastin time (PTT), preoperative international normalized ratio (INR), and
      preoperative platelet count were not statistically significant in predicting
      postoperative bleeding. Despite a more aggressive protocol for preoperative
      management of "high risk" patients, 5/10 (50%) experienced prolonged
      postoperative bleeding, with 3/5 (60%) requiring admission, while 1/5 (20%)
      experienced significant prolongation of their current inpatient stay. Review of
      the data showed that 5/9 (56%) of patients with 10 or more simple extractions
      developed long-term postoperative bleeding, all of whom had been classified in
      the "high risk" grouping. Admitted patients remained hospitalized an average of 4
      days (range of 1-6 days). CONCLUSION: Even with aggressive preoperative
      management, pretransplant liver failure patients requiring extraction of at least
      10 teeth prior to placement on the liver transplant list are at significant risk
      of long-term postoperative bleeding and hospital admission for its management.

PMID- 16982304
TI  - Failure strength of 2.0 locking versus 2.0 conventional Synthes mandibular
      plates: A laboratory model.
AB  - PURPOSE: This laboratory study compared the performance of locking versus
      nonlocking Synthes (Synthes, Paoli, PA) 2-mm mandibular fixation plates. The
      purpose of the study was to determine if there are physical or mechanical
      properties to support the use of one rigid fixation device over the other.
      MATERIALS AND METHODS: A bovine rib model was selected for this study because
      they closely approximate characteristics of the human mandible. Two experimental
      groups composed of 10 locking and 10 nonlocking 2-mm plates were secured to
      randomly selected osteotomized bovine ribs using 10-mm monocortical screws. The
      specimens were loaded using a 4-point bending system to the point of failure
      using a MTS model 309.00 servo-hydraulic testing system (MTS Systems Corp, Eden
      Prairie, MN) with a custom fabricated fixator. The data was obtained with
      TestStar 2 version 4.0 and TestWare Sx 4.0 software (MTS Systems Corp), and
      analyzed to determine if there was any difference in performance between the 2
      mandibular plate designs. RESULTS: Overall, there were no statistically
      significant differences between the locking and conventional 2-mm mandibular
      plate. Of the 20 samples tested, 1 (nonlocking) had a unique early screw failure
      (pullout) inconsistent with any other samples and was not analyzed. Of the
      remaining 19 samples, 17 produced a yield failure, bend, or stretch rather than a
      plate fracture. Both of the plate fractures occurred in the nonlocking plates.
      Although the data suggested that this mode of failure was more common in
      nonlocking plates, the difference between both groups in the mode of failure did
      not achieve statistical significance (chi2 = 2.0, P = .16). Thus, yield was the
      predominant mode of failure for both types of devices. The force at which each
      device failed was also similar in both groups. The force of failure for the
      nonlocking plates was 559.9 N (SD = 247.9), whereas the locking plate failure
      strength was 637.8 N (SD = 276.3; t (17) = 0.6, P = .53). The results indicated
      that there was no suggestion that one plate might be stronger than the other.
      CONCLUSIONS: In this laboratory model, no significant differences were found
      between the 2 types of mandibular plates. Although studies have shown the locking
      system to be more rigid, this study suggested that the type and degree of failure
      are more likely related to bone quality and surgical technique when using the 2
      mm mandibular plate. Additional prospective studies are needed to correlate these
      results in patient models.

PMID- 16982305
TI  - Relationship between the morphologies of the masseter muscle and the ramus and
      occlusal force in patients with mandibular prognathism.
AB  - PURPOSE: The purpose of this study was to examine the relationship between the
      morphologies of the masseter muscle and the ramus and occlusal force in patients
      with mandibular prognathism. PATIENTS AND METHODS: The study group consisted of
      71 patients with mandibular prognathism. They were divided into 2 groups,
      consisting of prognathism with or without symmetry, determined by frontal
      cephalogram analysis. All patients underwent 3-dimensional (3D) computed
      tomography (CT) and occlusal force was recorded with pressure-sensitive sheets.
      RESULTS: In the cross-sectional area of masseter muscle, there were no
      significant differences between the right and left sides in the symmetry and
      asymmetry groups. In occlusal force, there was no significant difference between
      the symmetry and asymmetry groups. Occlusal force was not significantly
      correlated to the cross-sectional area of the ramus, but it was significantly
      positively correlated to the cross-sectional area of the masseter muscle (P <
      .05). CONCLUSION: Occlusal force was associated with the ipsilateral cross
      sectional area of masseter muscle in patients with prognathism; however, it was
      not associated significantly with the degree of mandibular deviation.

PMID- 16982306
TI  - Reconstruction of mandibular condyle by transport distraction osteogenesis:
      Experimental study in rhesus monkey.
AB  - PURPOSE: This study investigated histomorphologic changes in the newly formed
      condyle reconstructed by transport distraction osteogenesis through a nonhuman
      primate model. MATERIALS AND METHODS: Six adult rhesus monkeys were used in this
      study. Bilateral condyles and articular discs were extirpated, and the technique
      of transport distraction osteogenesis was carried out to reconstruct the
      condyles. X-ray and 3-dimensional (3D) computed tomography (CT) scanning films
      were taken at various intervals. Two monkeys were killed respectively at 4, 12,
      and 24 weeks after completion of distraction; the transport segments and the
      distracted calluses were harvested and processed for histologic examination. The
      original condyles removed at surgery served as normal control. RESULTS: Open bite
      was seen in all animals postoperatively and diminished at the end of distraction.
      Bone regeneration was perfect in the distraction gap between the transport disc
      and the pre-existing mandible. The bony transport disc gradually remodeled to a
      neocondyle that was similar to the original condyle in the appearances and
      structures. The head of neocondyle was covered with a fibrous cap, which might
      play the role of an articular disc. CONCLUSION: A neocondyle with functional
      shape can be created by transport distraction osteogenesis. This suggests that
      this technique is an alternative method for reconstruction of the mandibular
      condyle.

PMID- 16982307
TI  - Clinical and anatomical study of retromolar foramen and canal.
AB  - PURPOSE: The retromolar canal is a rare anatomic variation of the mandible. The
      neurovascular content of the mandibular retromolar canal is very important for
      surgical procedures involving the retromolar area and there has been a lack of
      information on this subject. This study consists of anatomic research of the
      retromolar foramen and canal, planned after an impacted third molar tooth
      extraction operation in which we encountered a retromolar neurovascular bundle.
      MATERIALS AND METHODS: Eighty sides of 40 mandibles were evaluated and the
      presence of the retromolar foramen and its relation to the last teeth, the
      transverse and sagittal distances of the retromolar trigone, and the distance of
      the retromolar foramen to the last socket of the arch were measured. RESULTS: The
      neurovascular bundle includes striated muscle fibers, thin myelinated nerve
      fibers, numerous venules and a muscular artery. Of the 40 mandibles included in
      this study, retromolar foramens were found in 10 (25%). The presence of the
      retromolar foramen is not dependent on the last teeth of the arch. The dimensions
      of the retromolar trigone were measured and the presence of the retromolar
      foramen was found to be nonrelevant to the dimensions of the retromolar trigone.
      Retromolar foramen distance from the distal edge of the last socket of the arch
      was found to be 11.91 +/- 6.71 mm and 4.23 +/- 2.30 mm, respectively, from the
      second and third molars. CONCLUSIONS: This study therefore clearly establishes
      the incidence and importance of the retromolar canal. This study shows that the
      retromolar foramen and canal can be seen occasionally in routine dental surgery.
      Due to the neurovascular bundle passing through it, the retromolar canal and
      foramen must be kept in mind in all anesthetic and surgical approaches regarding
      the retromolar area and mandible.

PMID- 16982308
TI  - Bone regeneration in mandibular distraction osteogenesis combined with
      compression stimulation.
AB  - PURPOSE: This study compared modified distraction osteogenesis (DO) protocol with
      conventional DO protocol on healing bone formation. Computer simulation was
      performed to understand the mechanical environment of modified DO protocol, which
      applies compression during the consolidation period. MATERIALS AND METHODS: Fifty
      rats were used in this study. Twenty-five rats in the conventional DO (control)
      group were sacrificed at postoperative days 11, 21, 28, 35, and 49 after
      osteotomy. In the modified DO (experimental) group, compression was applied on
      day 7 after distraction (day 18 postoperatively) for 4 days during the early
      consolidation period and 25 rats were sacrificed on postoperative day 19, 28, 39,
      46, and 53. The histologic and radiographic findings were used to compare the 2
      groups. Further, computer simulation was used to predict the mechanical
      environment of healing bone under conventional and modified DO protocol. RESULTS:
      Radiographic findings showed that the experimental group resulted in denser and
      wider healing bone. Histologically, the experimental group yielded more mature
      lamellar bone than the control group. Computer simulation showed that absolute
      values of tissue strains were nearly double in the control group because of the
      softer healing tissues. Both the experimental and control groups showed high
      strains at the ridge crest. Concentrated tensile strain along the distraction
      direction at the ridge crest might hinder bone formation at the interface, while
      compressive strain could facilitate the process. CONCLUSION: This study proposed
      a modified DO protocol of adding compression during the early consolidation
      period of conventional DO protocol. This new technique appears to provide faster
      and denser bone regeneration.

PMID- 16982309
TI  - Comparison of mandibular rami width in patients with prognathism and
      retrognathia.
AB  - PURPOSE: The purpose of this study was to assess the ramus thickness in skeletal
      Class III and Class II patients. METHODS: Forty patients were evaluated using
      computed tomography scanning. RESULTS: Compared with the Class II patients, the
      mandibular ramus of Class III patients was thinner. The ramus thickness in
      retrognathic patients was 8.84 mm and the ramus thickness in prognathic patients
      was 7.80 mm. CONCLUSION: The ramus is thinner in patients with prognathism than
      in those with retrognathia.

PMID- 16982311
TI  - The effect of autogenous costochondral grafts on temporomandibular joint fibrous
      and bony ankylosis: A preliminary experimental study.
AB  - PURPOSE: The purpose of this study was to test the functional and histologic fate
      of costochondral grafts (CG) in temporomandibular joint (TMJ) reconstruction for
      unilateral ankylosis in the sheep. MATERIALS AND METHODS: Five pure-bred adult
      Merino sheep were used. Ankylosis was induced by articular damage, disc removal,
      and placement of a bone graft. At 3 months, a gap arthroplasty was performed with
      a CG from the thirteenth rib. The sheep were sacrificed 3 months after CG
      reconstruction. The range of jaw movements were recorded at first operation, at
      lysis of ankylosis, and at sacrifice. The joints were examined radiologically,
      macroscopically, and histologically. RESULTS: All sheep showed a decrease in
      masticatory function, as shown by weight loss and decreased jaw opening, during
      the ankylosis period. On release, they regained weight and increased the range of
      jaw movement. Histologically, the joint space was filled with fibrous tissue.
      However, the partial spaces around the CG head were covered by fibrous tissue
      and/or fibrous cartilage. CONCLUSIONS: This study shows that, when CGs are used
      with a gap arthroplasty in a fibrous and bony ankylosed TMJ, masticatory function
      is restored.

PMID- 16982310
TI  - Biomechanical evaluation of different types of rigid internal fixation techniques
      for subcondylar fractures.
AB  - PURPOSE: The aim of this study was to evaluate the biomechanical stability of
      various internal fixation systems for subcondylar fractures. MATERIALS AND
      METHODS: Eighteen identical synthetic mandibles were used. Left condylar
      processes were cut to mimic perpendicular subcondylar fracture and right sides
      were mimicked oblique subcondylar fracture. The fixation systems used included
      single 4-hole mini adaptation plate, double fixation with the same plates, single
      4-hole mini dynamic compression plate (DCP), Eckelt lag screw system, Wurzburg
      lag screw plate system and double 4-hole biodegradable miniplates made of poly L
      lactide (PLLA). In oblique fractures, one of the screws fixing plates was used
      bicortically through bone fragments. The loading vector simulated physiologic
      forces to the condyle on biting with servohydraulic testing machine until failure
      was reached. Load-displacement curve, maximum load for failure, and stiffness
      were measured. RESULTS: In perpendicular fracture, double adaptation plate showed
      the highest level of tolerance load followed by Eckelt lag and double PLLA plate.
      In stiffness, double adaptation plate and Eckelt lag screw showed higher level of
      stiffness, whereas double PLLA was almost at the same level of single DCP. In
      oblique fracture, double adaptation plate showed the highest strength.
      CONCLUSIONS: In this laboratory setting, double adaptation plates fixation proved
      to have superior biomechanical stability in both fracture conditions. Eckelt lag
      screw showed good stability in the perpendicular fracture, however, it was weak
      in the oblique fracture.

PMID- 16982312
TI  - The prevention of periodontal bone loss at the osteotomy site after anterior
      segmental and dento-osseous osteotomy.
AB  - PURPOSE: Degeneration of the gingival margin and periodontal bone loss between
      segments can occur in various segmental osteotomies. However, treatment and
      management of these problems have not yet been resolved; improvement of the
      conventional method is necessary. The purpose of this retrospective study is to
      evaluate the usefulness and advantage of orthodontic devices in osteotomies.
      PATIENTS AND METHODS: Forty Japanese adults presented with jaw deformities
      diagnosed as mandibular prognathism with maxillary protrusion, bimaxillary
      protrusion, and anterior crowding. Of these 40 patients, 20 (group 1) underwent
      anterior segmental osteotomy or dento-osseous osteotomy along with our original
      orthodontic periodontal management. The remaining 20 (group 2) patients underwent
      conventional procedures. After surgery, pocket depth and periodontal bone loss at
      the osteotomy site were evaluated. RESULTS: In all cases of patients who
      underwent our original technique, degeneration of the gingival marginal and
      periodontal defects at the osteotomy site were not found. The rate of alveolar
      bone height in group 1 significantly increased and that in group 2 significantly
      decreased after maxillary osteotomy (P < .05). CONCLUSION: This technique may
      prevent periodontal defects from occurring at the interdental osteotomy site.

PMID- 16982313
TI  - Surgical management of ameloblastoma in the mandible: Segmental mandibulectomy
      and immediate reconstruction with free fibula or deep circumflex iliac artery
      flap (evaluation of the long-term esthetic and functional results).
AB  - PURPOSE: Ameloblastoma is responsible for 1% of all the oral and
      maxillomandibular cysts and tumors. It is odontogenic in origin and benign in
      nature but it has a high percentage of local recurrence rate and possible
      malignant development when treated inadequately. With the advancement of
      craniofacial surgical techniques, use of free flaps for mandibular
      reconstruction, and dental rehabilitation (such as osseointegration), the
      segmental mandibulectomy and immediate reconstruction with free flaps are
      beginning to be used more effectively for the treatment of the mandibular
      ameloblastoma. The aim of this article is to evaluate the clinical results of the
      patients with mandibular ameloblastoma who were treated with segmental
      mandibulectomy and immediate reconstruction with free flaps. PATIENTS AND
      METHODS: We present 11 patients who had segmental mandibulectomy and immediate
      reconstruction with free deep circumflex iliac artery or fibular flap for
      treatment of mandibular ameloblastoma. The average age of the patients was 25.4
      years (range, 18-38 years). The patients were followed up for a mean of 29.3
      months (range, 17-38 months). The functional and esthetic results were also
      evaluated by using a questionnaire in the long term. The questionnaire consisted
      of questions addressing oral continence, diet, social activities, speech, and
      facial appearance. RESULTS: All flaps survived totally. Recurrence was not
      detected during the follow-up period. It was found that all patients had good
      esthetic and functional results after immediate reconstruction. The social
      activities of patients also were not affected after treatment. CONCLUSIONS: We
      experienced that segmental mandibulectomy with safe borders and immediate
      reconstruction with free fibula flap or deep circumflex iliac artery (DCIA) flap
      is an ideal treatment method for mandibular ameloblastoma. The functional and
      esthetic results are also detected as very satisfactory for the patients.

PMID- 16982314
TI  - Alveolar bone graft for patients with cleft lip/palate using bone particles and
      titanium mesh: A quantitative study.
AB  - PURPOSE: This study evaluated the bone volume, height, and width that can be
      obtained in alveolar ridge augmentation using titanium mesh and autogenous bone
      particles in patients with cleft lip/palate. PATIENTS AND METHODS: Subjects were
      15 patients with cleft lip/palate requiring tertiary bone graft for implant
      therapy. Computed tomography (CT) scans were taken before removing the mesh, from
      1 to 21 months after bone grafting. Forty-three reconstructed images
      corresponding to the positions for implant placement were selected for this
      study. The percent defect filled with bone (%BONE), defined as the percentage of
      newly formed bone in the space created by the mesh, was measured for image
      analyses. In linear analyses, 4 parameters were used: increased bone height
      (IBH), percent increased bone height (%IBH), increased bone width (IBW), and
      percent increased bone width (%IBW). Factors influencing the quantitative data
      and the clinical courses of placed implants were also explored. RESULTS: The
      average %BONE was 91.1%. IBH averaged 4.4 mm, whereas %IBH averaged 88.5%. IBW
      averaged 4.6 mm, whereas %IBW averaged 86.4%. Little correlation was present
      between the quantitative data and patient age, or time interval. A significant
      correlation was identified between the data for span of the grafted area and
      %BONE (correlation coefficient value = -0.36). However, the diminishing rate was
      very low. No implants were lost postoperatively. CONCLUSIONS: Alveolar ridge
      augmentation with titanium mesh and autogenous bone particles from the anterior
      iliac crest has very high predictability as a preimplant procedure in patients
      with cleft lip/palate.

PMID- 16982315
TI  - Image-guided minimally invasive surgical access to the temporomandibular joint: A
      preliminary report.
AB  - PURPOSE: To establish a protocol for image-guided minimally invasive surgical
      access to the temporomandibular joint (TMJ). MATERIALS AND METHODS: This study
      involved 2 patients with TMJ pain and mandibular motion dysfunction. Axial
      magnetic resonance imaging (MRI) of the TMJ was obtained and loaded into an intra
      operative navigation system to guide joint space injection. With a navigated
      syringe, 1 mL synvisc Hylan G-F 20 was directly injected into the superior and
      inferior joint spaces under navigation guidance. RESULTS: With the assistance of
      an intraoperative navigational system, the TMJ MRI images were visualized in 3
      dimensions and enabled guiding a needle into the superior and inferior joint
      spaces for therapeutic injection. The treatment outcome for both patients was
      satisfactory with improvement in pain score and mandibular motion. CONCLUSIONS: A
      protocol for image-guided minimally invasive surgical access to the TMJ was
      established. This could provide the technical basis for evaluation of accurate
      joint space intervention as a form of treatment of appropriate TMJ disorders.

PMID- 16982316
TI  - New fixation method for maxillary distraction osteogenesis using locking
      attachments.
AB  - PURPOSE: The external traction hooks of the intraoral splint used in the rigid
      external distraction (RED) system for maxillary distraction osteogenesis
      interfere with the surgical procedures. The purpose of this study is to introduce
      an innovative splint fixation method for maxillary distraction osteogenesis with
      Locking Attachments and evaluate their advantages, such as reduction of operating
      time compared with the traditional intraoral splint method. PATIENTS AND METHODS:
      Retrospective comparison of operative times of maxillary Le Fort I osteotomy
      procedures was carried out with the traditional protocol using the intraoral
      splint cemented to the maxillary dentition (n = 14), and a removable intraoral
      splint that is inserted postsurgically (n = 14). Operative procedure times were
      compared and analyzed statistically using the data extracted from the surgical
      records. RESULTS: There were no complications inserting the removable splint
      postsurgically, including pain, discomfort, or time-consuming procedure. Stable
      and secure splint fixation was obtained before the distraction procedure and the
      desired treatment goals were obtained in all patients. The total operative
      procedure times were significantly reduced in the Locking Attachments group by
      24% to 41% (approximately 65 minutes) compared with earlier operations involving
      the conventional splints (P < .05). CONCLUSIONS: Maxillary distraction
      osteogenesis with the Locking Attachments is a highly effective fixation approach
      to manage severe hypoplastic maxilla, eliminating lip constraints resulting from
      scarring and allowing for easier, more deliberate and careful dissection. The use
      of the Locking Attachments is reliable in craniofacial surgery and has proved to
      be advantageous in the reduction of the operating time and surgical risks.

PMID- 16982317
TI  - Transplantation of vascularized submandibular gland in dogs.
AB  - PURPOSE: Presently, treatments for xerostomia only target symptoms, as an active
      therapy method has not been established. Herein, we discuss the possibility of
      using a submandibular gland allograft technique for the disease. MATERIALS AND
      METHODS: Using a vascularized submandibular gland transplantation method, we
      extracted portions of the submandibular gland, including the duct and chorda
      tympani branches, from beagle dogs and placed them into the submental region of
      age- and weight-matched dogs. We then measured the amount of saliva secretion and
      examined the grafted glands histologically. RESULTS: Sufficient quantities of
      saliva were secreted from the grafted glands with pilocarpine treatment.
      Histologic findings showed that the acinar cells in the grafted and untreated
      contralateral glands had some atrophy, as compared with the normal glands;
      however, periodic acid Schiff staining showed that they produced saliva.
      CONCLUSIONS: Transplantation of vascularized submandibular glands into dogs was
      successful and may become a novel treatment strategy for patients with
      xerostomia.

PMID- 16982318
TI  - Upper lip reconstruction with the alar crescent flap: A new approach.
AB  - PURPOSE: The alar crescent advancement flap technique has been widely used for
      repair of large central defects of the upper lip and base of the nose because of
      its 1-stage procedural simplicity and good results. Several more complicated and
      multiple staged procedures that respect either structure or function, often
      compromising one to achieve the other, have become popular and have recently
      taken its place. However, these procedures are more complex and in many cases
      require a staged approach. In this study, we present a series of 33 patients who
      underwent reconstruction of large upper lip defects utilizing alar crescent flaps
      between 1992 and 2002. PATIENTS AND METHODS: A series of 20 patients underwent
      reconstruction of large upper lip defects using alar crescent flaps between 1992
      and 2002. Malignant etiologies were responsible for the defect in all patients.
      Reconstruction was performed as a 1-staged procedure in 19 cases. In 1 patient
      with a total upper lip defect, bilateral alar crescent flaps were used in
      conjunction with a cross lip flap that was later divided in a second stage
      procedure. RESULTS: All patients tolerated the procedure well with no major
      complications. Minor complications not requiring surgical intervention occurred
      in 5 patients. During the 12- to 60-month follow-up, all patients were found to
      be satisfied with the functional result. However, 7 patients underwent minor
      surgical procedures for esthetic improvement. There was no recurrence of disease
      in the 20 patients who underwent resection of malignancy. CONCLUSIONS: In these
      20 cases, we have shown the utility of the alar crescent flap for varying length
      partial and full-thickness reconstruction of upper lip defects. This simple and
      straightforward technique provided good functional and esthetic results. The
      disadvantage of this procedure is the loss of philtral anatomic detail. Its
      primary advantage is that it is a single-stage procedure with a relatively low
      morbidity and patient inconvenience. As a single-stage technique it satisfies
      concerns over cost containment over more complex and staged procedures while
      still providing a good functional and cosmetic result. Furthermore, for those
      same reasons, this procedure is a good first choice in the elderly.

PMID- 16982319
TI  - Tetracycline compound placement to prevent dry socket.

PMID- 16982320
TI  - Persisting alveolar sockets-a radiologic symptom of BP-ONJ?

PMID- 16982321
TI  - Chemokines in multiple myeloma.
AB  - OBJECTIVE: In this article we focus on the role that chemokines and chemokine
      receptors play in the pathogenesis of multiple myeloma and the associated bone
      destructive process, and consider their utility as novel therapeutic targets for
      treating this devastating disease. METHODS: Current research on the role that
      chemokine and chemokine receptors play in the pathogenesis of myeloma is
      reviewed. RESULTS: The chemokines, MIP-1alpha, MCP-1, IL-8, and SDF-1, and their
      receptors play important roles in homing of MM cells, tumor growth, and bone
      destruction in myeloma. They are attractive therapeutic targets for treating
      myeloma patients. CONCLUSION: Addition of chemokine antagonists to current
      treatment regimens for myeloma should result in better therapeutic responses
      because of the loss of both the protective effect of the marrow microenvironment
      on the MM cells and the induction of osteoclast activity.

PMID- 16982322
TI  - Sustained G-CSF plasma levels following administration of pegfilgrastim fasten
      neutrophil reconstitution after high-dose chemotherapy and autologous blood stem
      cell transplantation in patients with multiple myeloma.
AB  - OBJECTIVE: Pegfilgrastim has shown to decrease the duration of severe neutropenia
      after conventional chemotherapy, but its use after high-dose chemotherapy and
      autologous blood stem cell transplantation has not been established yet.
      Therefore we studied the efficacy and the pharmacokinetic profile of
      pegfilgrastim in patients with multiple myeloma undergoing high-dose
      chemotherapy. METHOD: In total, 21 patients received a single subcutaneous
      injection of 6 mg pegfilgrastim on day +1 after transplantation and pegfilgrastim
      plasma levels were measured daily by enzyme-linked immunosorbent assay. Clinical
      outcome was compared with pegfilgrastim levels of 282 plasma samples and data of
      a historical control group of patients without granulocyte colony-stimulating
      factor (G-CSF) support. RESULTS: Pegfilgrastim levels showed an inverse
      correlation (r = -0.68, p < 0.01) with neutrophil counts. Peak levels were
      reached at day +4 (94 ng/mL; range: 37-205) and were maintained until day +7 (85
      ng/mL; range: 35-186). Comparison with the control group without G-CSF support
      showed that time to neutrophil reconstitution was significantly shorter in the
      pegfilgrastim group with 10 vs 15 days, respectively (p < 0.001). There was no
      correlation of pegfilgrastim levels and the duration of neutropenia, although
      patients with a fivefold increase in neutrophil counts the day after
      pegfilgrastim administration had a significantly shorter median duration of
      neutropenia in comparison to patients who were less susceptible to G-CSF
      stimulation (5 vs 7 days, p < 0.01). CONCLUSION: Neutrophil reconstitution after
      high-dose chemotherapy could be accelerated by the use of pegfilgrastim in
      patients with myeloma. Responsiveness of neutrophils to pegfilgrastim before
      neutropenia was correlated with faster neutrophil reconstitution, whereas G-CSF
      levels had no impact on neutrophil recovery.

PMID- 16982323
TI  - Preclinical evaluation of Hematide, a novel erythropoiesis stimulating agent, for
      the treatment of anemia.
AB  - OBJECTIVE: To evaluate the preclinical erythropoiesis stimulating properties of
      Hematide, a novel, PEGylated, synthetic peptide for the treatment of anemia
      associated with chronic kidney disease and cancer. METHODS: The in vitro activity
      of Hematide was assessed in competitive binding, proliferation, signal
      transduction, and apoptosis assays, and in erythroid colony-forming assays with
      CD34(+) cells purified from human bone marrow. Erythropoiesis and
      pharmacokinetics were evaluated in rat, monkey, and a rat chronic renal
      insufficiency (CRI) model following single administration. Erythropoiesis and
      immunogenicity were also evaluated following repeat administration in rats.
      RESULTS: Hematide binds and activates the erythropoietin receptor and causes
      proliferation and differentiation of erythroid progenitor cells. Sustained
      circulatory persistence of Hematide is observed in rats and monkeys. In a rat CRI
      model, Hematide exhibited twofold lower clearance than in the normal rat, with
      hypothesis consistent with Hematide being cleared, at least partially, via the
      kidney. A dose-dependent rise in hemoglobin (Hgb) and duration of response was
      observed following single administration in rats and monkeys. Hematide was able
      to alleviate anemia in an experimental CRI rodent model. Repeat intravenous (IV)
      and subcutaneous (SC) administration in rats yielded similar erythrogenic
      responses, with no anti-Hematide antibodies being detected. CONCLUSIONS: Hematide
      is a potent erythropoiesis stimulating agent with a prolonged half-life and slow
      clearance times. It is anticipated that similar prolonged clearance and activity
      will be observed in the clinic, potentially enabling dosing intervals of 3 to 4
      weeks that may translate into improved patient convenience for the treatment of
      anemia.

PMID- 16982324
TI  - Evidence for downregulation of erythropoietin receptor in bone marrow erythroid
      cells of patients with chronic idiopathic neutropenia.
AB  - OBJECTIVE: The aim of this study is to probe the mechanisms underlying anemia in
      patients with chronic idiopathic neutropenia (CIN) by evaluating parameters of
      bone marrow (BM) erythropoiesis. PATIENTS AND METHODS: Ten CIN patients
      fulfilling the criteria of anemia of chronic disease, 27 nonanemic CIN patients,
      and 30 healthy volunteers were enrolled in the study. Reserves and survival
      characteristics of BM erythroid cells were evaluated using flow cytometry and
      clonogenic assays. Serum erythropoietin (EPO) was measured with ELISA. Expression
      of EPO receptors (EPORs) on BM erythroid cells was evaluated by flow cytometry
      and reverse-transcription polymerase chain reaction. RESULTS: CIN patients
      display defective erythropoiesis in addition to previously reported impaired
      granulopoiesis. Patients have low number of CD34(+)/CD71(+) progenitor and CD36(
      )/ Glycophorin A(+) (GlycoA(+)) precursor BM cells, and increased proportion of
      apoptotic cells within the CD34(+)/CD71(+) and CD36(+)/GlycoA(+) compartments.
      Burst-forming units erythroid (BFU-Es) in BM mononuclear or purified CD34(+)
      cells were significantly reduced in the patients. Patient BFU-Es increased
      significantly following in vitro treatment with tumor necrosis factor-alpha (TNF
      alpha) and/or interferon gamma (IFN-gamma)-neutralizing antibodies. Local TNF
      alpha and IFN-gamma production was higher in anemic than in nonanemic patients.
      EPO production was appropriate in the patients, but EPOR expression was
      significantly reduced in patient GlycoA(+) cells, especially in anemic patients.
      CONCLUSION: Impaired BM erythropoiesis in CIN patients is probably the result of
      increased local production of TNF-alpha and IFN-gamma that induce apoptosis, cell
      growth inhibition, and downregulation of EPOR expression on erythroid cells. We
      suggest that anemia in CIN patients displays overlapping pathophysiologic
      features with anemia of chronic disease.

PMID- 16982325
TI  - Erythropoietin induces sustained phosphorylation of STAT5 in primitive but not
      definitive erythrocytes generated from mouse embryonic stem cells.
AB  - OBJECTIVE: During embryonic development murine erythropoiesis occurs in two waves
      by producing first primitive erythroid cells (EryPs) and then definitive
      erythroid cells (EryDs). Erythropoietin (EPO) signaling is compared between EryPs
      and EryDs. METHODS: We studied the EPO signaling in EryPs and EryDs using an
      embryonic stem-derived culture system, which can recapitulate this in vivo
      development process and has thus been used as a convenient in vitro model system
      of erythropoiesis. RESULTS: We found that EPO induced sustained phosphorylation
      and nuclear translocation of signal transducer and activator of transcription 5
      (STAT5) in EryPs but not EryDs. EryPs expressed dramatically higher amounts of
      EPO receptor compared with EryDs, indicating there was excessive signaling from
      the receptor upon EPO stimulation. In addition, reduced expression of tyrosine
      phosphatase, Src homology region 2 domain-containing phosphatase-1, and decreased
      total phosphatase activity in EryPs partly explain the persistent activation of
      STAT5. Nevertheless, Janus kinase 2 (JAK2) phosphorylation, which is essential
      for transduction of EPO signaling from the EPO receptor to STAT5, was observed in
      a transient but not a persistent manner. Inhibition of JAK activity resulted in
      partial suppression of transient phosphorylation of STAT5 and no suppression of
      sustained phosphorylation of STAT5. CONCLUSION: This study presents a unique
      feature of EryPs, as this is the first known example of sustained activation of
      STAT5 in normal cells. Our results also imply the existence of a JAK2-independent
      pathway of EPO signaling to induce STAT5 activation.

PMID- 16982326
TI  - Stable gene transfer to human CD34(+) hematopoietic cells using the Sleeping
      Beauty transposon.
AB  - OBJECTIVE: Methods of gene transfer to hematopoietic stem cells that result in
      stable integration may provide treatments for many inherited and acquired blood
      diseases. It has been demonstrated previously that a gene delivery system based
      on the Sleeping Beauty (SB) transposon can be derived where a plasmid transiently
      expressing the SB transposase can mediate the stable chromosomal integration of a
      codelivered second plasmid containing a gene expression unit flanked by the
      inverted repeats derived from the transposon. METHODS: Plasmid DNA containing the
      elements required for SB transposition was delivered to hematopoietic cells via
      electroporation. Integrated transgene (enhanced green fluorescent protein [eGFP])
      expression was assessed in vitro and in vivo. RESULTS: In the K562 human
      hematopoietic cell line, we observed stable expression of eGFP in >60% of cells
      for over 2 months after electroporation of the two plasmids; in contrast, in
      control cells either not treated with transposase or exposed to a defective
      mutant transposase, the level of gene expression had fallen to near background
      (<0.1%) by 2 weeks. In purified human cord blood CD34(+) progenitor cells, the
      transposase led to stable gene transfer at levels up to 6% for over 4 weeks, but
      gene transfer to more primitive nonobese diabetic/severe combined immunodeficient
      repopulating cells or CD34(+)/CD38(-) in long-term culture was low and
      electroporation of the cells with plasmid DNA caused significant cell death.
      CONCLUSION: The long-term stable expression highlights the potential of this
      transposase-based gene delivery method for ameliorating diseases affecting the
      hematopoietic system, although further improvements in gene transfer efficacy are
      needed.

PMID- 16982327
TI  - High-efficient lentiviral vector-mediated gene transfer into primary human NK
      cells.
AB  - OBJECTIVE: The long-term transfection of genes into primary natural killer (NK)
      cells without disrupting normal cellular functions has been proven to be
      difficult with currently available gene-transfer methods. In this study, we
      establish a lentiviral vector-based technique for improved gene transfer into
      human NK cells in vitro and we report on high-efficient transduction of freshly
      isolated as well as cultured primary NK cells. METHODS: Freshly isolated or
      primary cultured human NK cells, as well as the human NK cell line YTS, were
      transduced with replication-incompetent human immunodeficiency virus (HIV)-based
      lentiviral vector bearing a GFP reporter gene or a gene of interest under the
      control of the elongation factor 1alpha (EF1alpha) promoter. Transduction
      efficiencies were monitored by flow cytometry. RESULTS: A long-term transgene
      expression was detected in up to 98% of YTS NK cells, whereas in freshly isolated
      or primary cultured NK cells exposed to interleukin (IL)-2 plus IL-12 upon
      infection, efficiency was in the range of 50% to 90%. Moreover, in freshly
      isolated quiescent NK cells a transfection efficiency of 18% to 20% was achieved
      without stimulation. Notably, no major phenotypic and functional modifications
      were observed in transduced cells with respect to control cells: the expression
      levels of activating receptors, CD69-antigen induction as well as cytotoxic
      function were unaffected. CONCLUSION: Results of our study demonstrate that NK
      cells can be efficiently transduced by lentiviral vectors.

PMID- 16982328
TI  - A Stro-1(+) human universal stromal feeder layer to expand/maintain human bone
      marrow hematopoietic stem/progenitor cells in a serum-free culture system.
AB  - OBJECTIVE: To compare the ability of allogeneic versus autologous purified human
      Stro-1(+) mesenchymal stem cell (MSC) populations from different human donors to
      support the ex vivo expansion and maintenance of human hematopoietic
      stem/progenitor cells (HSCs). Furthermore, we compared the results obtained with
      MSC as a feeder layer to traditional allogeneic stromal layers grown in long-term
      bone marrow culture media (LT-ST). METHODS: Adult human bone marrow CD34(+)
      enriched cells were cultured in serum-free medium for 2 to 3 weeks over the
      respective MSC-irradiated feeder layers or over traditional allogeneic LT- ST
      stromal layers in the presence of stem cell factor, basic fibroblast growth
      factor, leukemia inhibitory factor, and Flt-3 and analyzed every 2 to 4 days for
      expansion, phenotype, and clonogenic ability. RESULTS: There was a progressive
      expansion of total numbers of cells in all the experimental groups; however,
      allogeneic MSCs were more efficient at expanding CD34(+)CD38(-) cells and showed
      a higher clonogenic potential than both allogeneic LT-ST and autologous MSCs. The
      differentiative potential of cells cultured on both MSC and LT-ST was primarily
      shifted toward myeloid lineage; however, only MSCs were able to maintain/expand a
      CD7(+) population with lymphocytic potential. Importantly, transplantation into
      preimmune fetal sheep demonstrated that the HSCs cultured over MSCs retained
      their engraftment capability. CONCLUSION: These results indicate that purified
      Stro-1(+) MSCs may be used as a universal and reproducible stromal feeder layer
      to efficiently expand and maintain human bone marrow HSCs ex vivo.

PMID- 16982329
TI  - Constitutive c-jun N-terminal kinase activity in acute myeloid leukemia derives
      from Flt3 and affects survival and proliferation.
AB  - OBJECTIVE: c-jun N-terminal kinase (JNK) has been implicated in proliferation and
      survival downstream from the tyrosine kinase oncogene, p210 BCR-ABL, in chronic
      myeloid leukemia. We studied whether a similar relationship between JNK and FMS
      like tyrosine kinase 3 (Flt3) describes acute myeloid leukemia (AML). METHODS: By
      immunoprecipitation, Flt3 was found to be activated and identified as the
      potential origin of JNK activity in a heavy majority of JNK+ve AML blasts tested.
      Often, Flt3 activity is associated with activating mutation of the gene locus.
      However, statistical linkage tied JNK activity with Flt3 expression levels rather
      than with mutation. An adaptor network to describe the signal cascade Flt3-to-JNK
      was uncovered. RESULTS: Active Flt3 was linked to p85 phosphoinositide-3 (PI-3)
      kinase, and p85 with cbl and CrkII/CrkL by co-immunoprecipitaton assays from
      lysates of model cell lines and primary AML blasts. JNK1 co-immunoprecipitated
      from such lysates with p85-cbl-crkII/L and bound to Crk species SH3 domain in
      pull-down assay. siRNA-mediated depletion of Flt3 or of cbl, the adaptor at the
      nexus of this signaling group, inhibited JNK activity on substrate c-jun. Within
      AML blast cells influenced by Flt3 signaling, selective inhibition of JNK by a
      small molecule inhibitor, led to proliferative inhibition, apoptosis, and
      sensitizing cells to the anthracycline, daunorubicin. These effects occurred upon
      JNK inhibition without off-target inhibition of extracellular signal-regulated
      kinase or AKT pathways, and p38-kinase activation, an effector in the p53/p14 arf
      tumor suppressor pathway, was also maintained or augmented. CONCLUSION: JNK is a
      bonafide signaling pathway from Flt3 in AML whose function for proliferation and
      survival is required in a significant AML cohort with active Flt3 signaling, by
      mutation or overexpression of Flt3.

PMID- 16982331
TI  - JTE-607, a multiple cytokine production inhibitor, ameliorates disease in a SCID
      mouse xenograft acute myeloid leukemia model.
AB  - OBJECTIVE: Accumulating findings suggest that in acute myeloid leukemia (AML)
      patients, proinflammatory cytokines and growth factors play important roles in
      the proliferation and survival of AML cells in an autocrine and paracrine manner,
      leading to deterioration of AML. JTE-607 is a multiple cytokine inhibitor that
      potently suppresses production of proinflammatory cytokines. In the present
      study, we investigated the potency of JTE-607 as an antileukemic agent by
      exploiting a SCID mouse acute leukemia model. METHODS: SCID mice injected with
      anti-asialo-GM1 antibody were exposed to sublethal total-body irradiation at a
      dose of 3 Gy and then inoculated intravenously with AML cells. JTE-607 was
      administered using osmotic minipumps. The effects of JTE-607 on mouse survival
      time, human interleukin (IL)-8 levels in mouse plasma, and proportion of human
      CD45(+) cells in the bone marrow were studied. RESULTS: The survival time of the
      mice was strictly dependent on the number of U-937 cells proliferating in vivo.
      Administration of JTE-607 during the initial 7 days significantly prolonged
      survival of the mice, suggesting killing activity of JTE-607 against AML cells in
      vivo. Delayed administration of JTE-607 also prolonged the survival of mice
      bearing established leukemia with an effect comparable to the maximum tolerable
      dose of cytarabine. Flow cytometer analysis of bone marrow cells revealed
      decreased number of human CD45(+) cells. Human IL-8 level was also reduced by JTE
      607. CONCLUSION: Our results indicate that JTE-607 has potential to be a new
      class of antileukemic drug that exerts inhibitory activities against both the
      proliferation and proinflammatory cytokine production of AML cells.

PMID- 16982330
TI  - Cytotoxic and biochemical effects of 3,3',4,4',5,5'-hexahydroxystilbene, a novel
      resveratrol analog in HL-60 human promyelocytic leukemia cells.
AB  - OBJECTIVE: Resveratrol (3,4',5,-trihydroxystilbene, RV), an ingredient of wine,
      is an inhibitor of the proliferation-linked enzyme ribonucleotide reductase (RR)
      and shows a broad spectrum of cytotoxic effects against human cancer cells. In
      order to enhance these effects, we introduced additional hydroxyl moieties into
      the molecule. In the present study, the activity of a novel RV analog,
      3,3',4,4',5,5'-hexahydroxystilbene (M8), was investigated in HL-60 human
      promyelocytic leukemia cells. METHODS: Cytotoxicity of M8 alone or in combination
      with Ara-C was assessed employing growth inhibition assays. Effects of M8 on
      nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) were
      examined by HPLC. The apoptotic potential of M8 and RV was compared using a
      specific double-staining method and inhibition of TNF-alpha-induced activation of
      NF-kappaB was studied. Cell-cycle distribution was analyzed by FACS. RESULTS:
      Addition of ascorbic acid decreased the IC(50) value of M8 from 6.25 microM to 2
      microM. M8 depleted dATP and dTTP pools to 41% and 21% of control values, whereas
      dCTP pools increased to 199% of untreated controls. In addition, TTP, ATP, CTP,
      and GTP concentrations were decreased while UTP concentrations increased. M8
      induced apoptosis at concentrations significantly lower than RV and could
      remarkably inhibit the activation of NF-kappaB. M8 arrested cells in the S phase
      of the cell cycle while depleting cells in the G2-M phase and exhibited
      synergistic combination effects when applied simultaneously with Ara-C.
      CONCLUSION: Due to these promising results, this novel polyhydroxylated stilbene
      derivative might become an additional option for the treatment of leukemia and
      therefore deserves further preclinical and in vivo testing.

PMID- 16982332
TI  - Evaluation of liposomal clodronate in experimental spontaneous autoimmune
      hemolytic anemia in dogs.
AB  - OBJECTIVES: Liposomal clodronate (dichloromethylene diphosphonate) has been used
      to deplete macrophages and block clearance of opsonized cells in mouse models of
      autoimmune disease. However, liposomal clodronate (LC) has not been previously
      evaluated in a large-animal spontaneous autoimmune disease model. Therefore, the
      safety and efficacy of LC treatment was assessed in normal dogs and in dogs with
      spontaneous autoimmune hemolytic anemia (AIHA). METHODS: LC was administered
      intravenously first to healthy dogs and then to dogs with spontaneous, severe
      AIHA to determine if the treatment was safe and could block clearance of
      opsonized red blood cells (RBCs) in vivo. Studies were also conducted to assess
      the in vitro effects of LC on dog macrophages and dendritic cells. RESULTS:
      Intravenous infusion of low doses of LC was well tolerated and blocked clearance
      of opsonized RBCs in normal dogs in vivo. LC was taken up by splenic macrophages
      and dendritic cells in vivo, and induced killing of macrophages and dendritic
      cells in vitro. Seven dogs with severe, spontaneous AIHA were treated with LC in
      a pilot study. Treatment was well tolerated, 2 of 7 LC-treated dogs with AIHA had
      a decrease in RBC clearance, and LC-treated dogs had significantly increased
      survival times compared to historical control dogs matched for disease severity.
      CONCLUSIONS: These results indicate that LC can be safely administered
      intravenously to dogs and that even relatively low doses are capable of blocking
      RBC clearance and improving outcomes in a spontaneous large-animal model of AIHA.
      Therefore, additional studies of LC for treatment of autoantibody-mediated
      cytopenias in dogs and humans may be warranted.

PMID- 16982333
TI  - Dendritic cells pulsed or fused with AML cellular antigen provide comparable in
      vivo antitumor protective responses.
AB  - OBJECTIVE: To investigate whether syngeneic BM-derived DCs generated in vitro and
      fused with syngeneic C1498 tumor cells (murine AML line) could induce a better
      antitumor protective effect compared to similarly generated DCs pulsed with C1498
      lysate with or without co-injection of a class B CpG oligodeoxynucleotide (CpG
      7909) in vivo. METHODS: DCs were pulsed with C1498 lysate prior to intravenous
      administration 14 and 7 days prior to tumor challenge. Separate cohorts received
      DCs electrically fused to irradiated C1498 cells. Cohorts were administered DCs
      that were lysate-pulsed or fused with tumor cells on days 14 and 7 prior to tumor
      injection. Some cohorts were co-injected with CpG 7909 at the time of DC
      administration. RESULTS: All DC vaccines significantly improved survival (p <
      0.01) vs nonvaccinated controls. There was no difference in the antitumor
      protective response between mice that received pulsed vs fused DCs (47% vs 45%
      survival). Both DC vaccines generated a fivefold increase in splenic tumor
      reactive cytotoxic T-lymphocyte precursor cells and significantly (p < 0.05)
      higher mean frequencies of IFN-gamma-producing splenocytes compared to controls.
      CpG 7909 improved the survival of mice receiving the fused DCs (p < 0.05) but not
      the pulsed DCs. Surviving mice were rechallenged and found to be resistant to
      lethal tumor injection. CONCLUSIONS: DC vaccine strategies may be effective in
      generating anti-AML responses. No advantage was observed between lysate-pulsed
      and tumor cell-fused DCs. CpGs may provide an adjuvant effect depending on the
      type of DC vaccine administered.

PMID- 16982334
TI  - In vitro analysis of multipotent mesenchymal stromal cells as potential cellular
      therapeutics in neurometabolic diseases in pediatric patients.
AB  - Multipotent mesenchymal stromal cells (MSCs) play an important role in stromal
      support for hematopoietic stem cells, immune modulation, and tissue regeneration.
      We investigated their potential as cellular therapeutic tools in neurometabolic
      diseases as a growing number of affected children undergo to bone marrow
      transplantation. MSCs were isolated from bone marrow aspirates and expanded ex
      vivo under various culture conditions. MSCs under optimal good medical practice
      (GMP)-conform culture conditions showed the typical morphology, immunophenotype,
      and plasticity. Biochemically, the activities of beta-hexosaminidase A, total
      beta-hexosaminidase, arylsulfatase A (ASA), and beta-galactosidase measured in
      MSCs were comparable to those in fibroblasts of healthy donors. These four
      enzymes were interesting for their expression in MSCs, as each of them is
      defective, respectively, in well-known neurometabolic diseases. We found that
      MSCs released significant amounts of ASA into the media. In coculture
      experiments, fibroblasts from patients with metachromatic leukodystrophy, who are
      deficient for ASA, took up a substantial amount of ASA that was released into the
      media from MSCs. Mannose-6-phosphate (M6P) inhibited this uptake, which was in
      accordance with the M6P receptor-mediated uptake of lysosomal enzymes. Taken
      together, we show that MSCs produce appreciable amounts of lysosomal enzyme
      activities, making these cells first-choice candidates for providing metabolic
      correction when given to enzyme-deficient patients. With the example of ASA, it
      was also shown that an enzyme secreted from MSCs is taken up by enzyme-deficient
      patient fibroblasts. Given the plasticity of MSCs, these cells represent an
      interesting add-on option for cellular therapy in children undergoing bone marrow
      transplantation for lysosomal storage diseases and other neurometabolic diseases.

PMID- 16982335
TI  - Activation of cyclic AMP pathway prevents CD34(+) cell apoptosis.
AB  - OBJECTIVE: Although cAMP is involved in a number of physiologic functions, its
      role in hematopoietic cell fate decision remains poorly understood. We have
      recently demonstrated that in CD34(+)-derived megakaryocytes, cAMP-related agents
      prevent apoptosis. In this study we addressed the question of whether cAMP also
      regulates survival of their precursors, CD34(+) cells. METHODS: Apoptosis was
      evaluated by fluorescence microscopy, and detection of hypodiploid or annexin
      V(+) cells by flow cytometry. Mitochondrial membrane potential and bcl-xL or
      caspase-3 expression were assessed by flow cytometry. Colony-forming units were
      studied by clonogenic assays in methylcellulose. RESULTS: We found that two
      different cAMP analogs such as Dibutiril-cAMP and sp-5,6-DCl-BIMPS (BIMPS)
      promoted survival of human umbilical cord-derived CD34(+) cells by suppressing
      apoptosis induced by either nitric oxide (NO) or serum deprivation. Involvement
      of PKA and PI3K pathway was demonstrated by the ability of their specific
      inhibitors Rp-cAMP and Wortmannin or LY294002 respectively to reverse the
      antiapoptotic effect of BIMPS. Treatment of CD34(+) cell with BIMPS not only
      restrained the bcl-xL downregulation but also suppressed the loss of
      mitochondrial membrane potential and caspase-3 activation induced by serum
      starvation. While thrombopoietin (TPO), granulocyte colony-stimulating factor (G
      CSF) or stem cell factor (SCF) were not able to increase cAMP levels, the
      antiapoptotic activity exerted by these growth factors was blocked by inhibition
      of the adenylate cyclase and synergized by BIMPS. Cyclic AMP analogs suppressed
      the decreased colony formation in cells exposed to NO or serum deprivation.
      CONCLUSION: Altogether, our results strongly suggest that cAMP appears to be not
      only a key pathway controlling CD34(+) survival, but also a mediator of the TPO-,
      G-CSF- and SCF-mediated cytoprotection.

PMID- 16982336
TI  - Low percentages of circulating CD8(+)/CD45RA(+) human T lymphocytes expressing
      beta7 integrin correlate with the occurrence of intestinal acute graft-versus
      host disease after allogeneic hematopoietic stem cell transplantation.
AB  - OBJECTIVE: Effector phase of acute graft-versus-host disease (a-GVHD) is mainly
      mediated by donor-derived, anti-host cytotoxic T cells. T-cell homing into gut
      associated lymphoid tissues is ascribed to the alpha4beta7 integrin. We reasoned
      that development of intestinal a-GVHD might be triggered by recruitment in the
      intestinal mucosa of circulating, alloreactive, alpha4beta7(+) donor T cells.
      Therefore, we evaluated the correlation existing between circulating beta7(+) T
      lymphocyte subsets early after allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) and occurrence of a-GVHD. PATIENTS AND METHODS: Surface expression of
      beta7 integrin on T cells was evaluated by means of direct immunofluorescence, in
      three-color analysis. Sixty-five patients given allo-HSCT were evaluated: 13 of
      them experienced intestinal a-GVHD, 14 developed a-GVHD without intestinal
      involvement, and 38 did not develop a-GVHD. Patients were studied early after
      initial signs of hematologic reconstitution and before occurrence of a-GVHD.
      RESULTS: We found a significantly higher absolute number of CD8(+) and a
      significantly lower percentage of CD8(+)CD45RA(+)beta7(+) T cells in patients
      with intestinal a-GVHD than in patients with a-GVHD without intestinal
      involvement (p = 0.003 and p = 0.003, respectively) or not experiencing a-GVHD (p
      = 0.02 and p = 0.002, respectively). In particular, we found that intestinal a
      GVHD occurred in over 70% of patients showing an absolute number of CD8(+) T
      cells > or = 60 x 10(6)/L and a percentage of circulating CD8(+)CD45RA(+)beta7(+)
      T cells < 35%. CONCLUSION: Measuring the absolute number of CD8(+) T cells and
      percentage of CD8(+)CD45RA(+)beta7(+) T cells at time of hematologic
      reconstitution may help identify patients at risk of developing intestinal a-GVHD
      who could benefit from strategies aimed at hampering alloreactive T-cell homing
      to intestinal mucosa.

PMID- 16982340
TI  - Emergency medicine and the health of the public: the critical role of emergency
      departments in US public health.
AB  - This issue of the Emergency Medicine Clinics of North America focuses on the
      spectrum of public health issues that significantly impact the practice of
      emergency medicine and which are faced by practicing emergency physicians on
      daily basis. Topics include public health research in the emergency department;
      respiratory threats; emerging infectious diseases; emergency department
      overcrowding; end-of-life care; racial and ethnic disparities; issues of health
      promotion and disease prevention encompassing substance abuse, alcohol, and
      injury and violence; and public health surveillance; and the problems of homeless
      and disadvantaged patients. This article gives a brief introduction to the
      important relationship between emergency medicine and public health.

PMID- 16982337
TI  - Mannan-binding lectin pathway deficiencies and invasive fungal infections
      following allogeneic stem cell transplantation.
AB  - OBJECTIVE: The Mannan-binding lectin (MBL) pathway involves recognition of fungal
      surfaces by MBL and cleavage of C2 and C4 by MBL-associated serine protease
      (namely, MASP-2). Recent data show that MBL pathway deficiency might result not
      only from polymorphisms of the MBL2 gene but also of MASP2. The aim of the study
      was to assess whether polymorphisms of these genes are associated with invasive
      fungal infections (IFIs) following allogeneic stem cell transplantation (allo
      SCT). METHODS: The promoter and the exon 1 of MBL2 and the exon 3 of MASP2 were
      sequenced in 106 donor-recipient pairs from HLA-identical sibling allo-SCTs
      performed in a single institution. RESULTS: Ten percent of the donors and 11% of
      the recipients carried the MBL-low (O/O, LXA/O) genotypes; 7% of the donors and
      3% of the recipients were heterozygous for the MASP2 Asp105Gly variant. Factors
      associated with a higher probability of IFIs were donor's MBL-low genotype (38%
      vs 12%, p = 0.01), recipient's MASP2 variant (67% vs 14%, p = 0.01), and acute
      graft-versus-host disease (GVHD) grades II to IV (27% vs 11%, p = 0.04); in the
      multivariate analysis MBL-low genotype (relative risk [RR] 7.3, p = 0.003), MASP2
      variant (RR 6.4, p = 0.002), and acute GVHD II to IV (RR 3.8, p = 0.02) retained
      independent prognostic value. CONCLUSION: These results show for the first time
      that polymorphisms responsible for not only MBL but also MASP-2 deficiency are
      independent predictive factors for IFI after allo-SCT.

PMID- 16982341
TI  - Emergency department crowding: old problem, new solutions.
AB  - Emergency department (ED) crowding is becoming an increasing problem in EDs
      throughout the United States for a multitude of reasons, including an increase in
      patient volume and a decrease in available EDs. Crowding has an adverse impact on
      the ability to deliver quality and timely care and may contribute to adverse
      patient outcomes. Conceptually, factors that contribute to ED crowding can be
      divided into three domains, which correspond to their "sites of action": input,
      throughput, and output. A number of measures have been developed to better
      quantify crowding and its effects. More research needs to be done to better
      understand the factors that contribute to crowding, the impact of this problem on
      patients and ED throughput, and how to alleviate this nationwide crisis.

PMID- 16982342
TI  - The role of the emergency department in the care of homeless and disadvantaged
      populations.
AB  - This article provides an overview of the role of the emergency department (ED) in
      the care of homeless and disadvantaged populations. It suggests that organized
      emergency medicine can have a significant impact on total community health by
      maintaining a universal "safety net" for the delivery of integrated health and
      human services. The epidemiology of social deprivation among ED patients is
      examined, with a particular focus on homelessness. Current research on the value
      of socio-medical integration in the ED setting is discussed, with emphasis on
      selected initiatives that have demonstrated feasibility, cost-effectiveness, and
      impact.

PMID- 16982343
TI  - Health promotion and disease prevention in the emergency department.
AB  - This article provides an overview of health promotion and disease and injury
      prevention concepts. It provides an emergency medicine perspective and reviews
      approaches that can be used in the emergency department. It discusses examples of
      innovative emergency medicine-based preventive activities including prevention in
      the prehospital setting. This article ends with a discussion of the importance of
      a system approach to prevention and suggests a role for a preventionist as a new
      member of the emergency medicine team.

PMID- 16982344
TI  - Injury prevention.
AB  - Emergency medicine plays a significant role in injury prevention through the use
      of public health models that link injury data to prevention programming,
      research, and advocacy. The day-to-day experiences in the emergency department
      provide a picture of the injury problem in a given community and give the
      emergency practitioner a real-world basis for injury prevention efforts. This
      article covers the basics or injury prevention, including defining the problem,
      discussing data and conceptual aspects of injury prevention, and systematically
      identifying successful approach to reducing the burden of injuries.

PMID- 16982345
TI  - The relationship between intimate partner violence and other forms of family and
      societal violence.
AB  - Intimate partner violence was previously considered a private matter sometimes
      requiring law enforcement intervention. It is increasingly accepted as not only a
      medical issue for the victim, but a public and safety issue. Some of these other
      related issues, including unplanned pregnancy, same-sex relationships, overlap
      with elder, child, and animal abuse, and effects on workplace and school violence
      are explored. Screening, medical manifestations, documentation, reporting
      intervention, and referral are also discussed.

PMID- 16982346
TI  - Racial and ethnic disparities in the emergency department: a public health
      perspective.
AB  - This article discusses racial and ethnic disparities from a public health
      perspective, specifically why they threaten to impede the efforts to improve the
      nation's health. The authors (1) provide background information, including a
      review of the Institute of Medicine report on health care disparities; (2)
      describe the racial and ethnic compositions of the individuals in the emergency
      department setting from the perspective of both the patient and health care
      provider; (3) discuss the most prevalent disease presentations to the emergency
      department that are likely to have racial and ethnic disparities; and (4) give
      conclusions and general recommendations on how to address disparities in
      emergency health care.

PMID- 16982347
TI  - The impact of alcohol, tobacco, and other drug use and abuse in the emergency
      department.
AB  - Alcohol, tobacco, and other drug use is a significant societal problem.
      Individuals who use these substances are frequently seen in emergency departments
      at rates disproportionately greater than their population prevalence. This
      article highlights the impact of these drugs on patients and on emergency
      departments, including common presenting problems of individuals on these
      substances. Also discussed is how to help and to refer individuals with substance
      abuse problems through brief motivational interventions.

PMID- 16982348
TI  - Death, dying, and last wishes.
AB  - Issues regarding patient care near the end of life can be challenging and
      rewarding for emergency physicians. Knowledge of the patient's wishes is
      essential, and may be accomplished by advance directives or communication with
      patients and surrogates. Resuscitative efforts are appropriate for many patients,
      but inappropriate for others. The goals of medicine remain the following:
      providing optimal health care, provision of the best possible symptom control,
      communication, empathy, and caring. As death approaches, provision of the best
      possible medical care, in accordance with the patient's wishes, can be rewarding
      for patients, families, and health care providers.

PMID- 16982349
TI  - Communicable respiratory threats in the ED: tuberculosis, influenza, SARS, and
      other aerosolized infections.
AB  - Respiratory infections are the most common communicable infectious diseases. EDs
      are the front line for patients with respiratory infections because of their
      acute nature and because the ED is the principal site of health care for those at
      highest risk. These diseases include influenza, tuberculosis, and measles,
      together accounting for 25% of infectious causes of death worldwide. These are
      emerging and biothreat agents that follow the same route of transmission, such as
      pneumonic plague. We discuss epidemiology, pathogenesis, diagnosis, and treatment
      of each agent. Emphasis is on the ED's role as a public health prevention arena,
      with attention to education and disease prevention, early identification of
      disease in patients at risk, and reduction of illnesses.

PMID- 16982350
TI  - Emergency medicine and the public's health: emerging infectious diseases.
AB  - In recent years, multiple global forces have contributed to the emergence and
      widespread distribution of previously unknown disease entities. This article
      discusses Ebola virus, West Nile virus, and Hantavirus as representative emerging
      infectious diseases. Smallpox is discussed along with concerns about the safety
      of the smallpox vaccine, given the uncertain risk of bioterrorism and smallpox
      exposure. ED physicians must become familiar with the presentation, management,
      and public health impact of all of these entities, as well as understand the
      potential impact of other emerging infectious diseases.

PMID- 16982351
TI  - Update on public health surveillance in emergency departments.
AB  - The development of public health surveillance systems based on ED visits, in
      conjunction with other health and non-health-related data, is an important step
      to better understanding the health needs of the US population. There are multiple
      steps to develop a functional organization, and these actions require the support
      and involvement of many different partners. The ability to (1) analyze data; (2)
      distribute results; and (3) influence policy, funding, and patients' behavior are
      important outgrowths of these activities. This chapter discusses the
      opportunities and obstacles related to public health surveillance systems based
      on ED data.

PMID- 16982352
TI  - The future of emergency medicine public health research.
AB  - This chapter addresses past successes and challenges and then elaborates on the
      potential for further advances in three areas that bridge emergency medicine and
      the broader public health and health services research agenda: (1) monitoring
      health care access; (2) surveillance of diseases, injuries, and health risks; and
      (3) delivering clinical preventive services. This article also suggests ways to
      advance policy-relevant research on systems of health and social welfare that
      impact the health of the public.

PMID- 16982353
TI  - Predictors of in-hospital delay to reperfusion in patients with acute myocardial
      infarction in Japan.
AB  - The purpose of this study was to identify factors associated with in-hospital
      delay in patients with acute myocardial infarction (AMI) in Japan. In this
      observational study, 155 consecutive patients admitted with AMI to one of five
      urban hospitals were studied. The median door-to-needle time and door-to
      catheterization-laboratory time was 19 min and 60 min, respectively. Three
      variables predicted door-to-catheterization-laboratory times >/= 60 min: failing
      to call an ambulance, direct admission to the hospital, and absence of
      diaphoresis (p < 0.05). These findings support the need for public education
      emphasizing the importance of calling an ambulance for AMI symptoms. Moreover,
      Japanese physicians should be aware that admitting patients directly to the
      hospital and bypassing the Emergency Department might increase delay to
      treatment.

PMID- 16982354
TI  - The Pittsburgh Decision Rule: triage nurse versus physician utilization in the
      emergency department.
AB  - The Pittsburgh Decision Rule (PDR) is a rule for ordering knee radiographs in
      patients with acute knee injuries. This study was designed to compare the
      utilization of the PDR between triage nurses and physicians. Consecutive patients
      presenting to the Emergency Department were enrolled. Nurses and physicians were
      blinded to each other's examinations. Of 182 subjects approached, 30 were
      excluded for incomplete data or refusal to obtain radiographs, leaving 152
      subjects enrolled. Thirteen fractures (8.6%) were identified. Kappa scores were
      high for each component of the rule: mechanism of injury (fall or blunt trauma)
      kappa = 0.67, age (< 12 or > 50 years) kappa = 1, inability to ambulate kappa =
      0.67 and overall kappa = 0.83. Four of 13 fractures (31%) would have been missed
      using the PDR, resulting in a sensitivity of 77% for both physicians and nurses,
      and a specificity of 57% for physicians and 58% for nurses. Triage nurses and
      physicians were able to apply the PDR to patients who presented with acute knee
      injuries with a high level of agreement. However, the PDR demonstrated poor
      sensitivity in this patient population.

PMID- 16982355
TI  - Lidocaine-induced altered mental status and seizure after hematoma block.
AB  - Hematoma blocks with lidocaine are routinely utilized in the Emergency Department
      to allow reduction of Colles' fractures. Lidocaine toxicity is a potential
      complication of this procedure. We present a case report of a patient who
      developed acute mental status changes and generalized seizure immediately
      following administration of lidocaine during a hematoma block. The rapid onset of
      seizure development following injection was most likely due to inadvertent
      intravascular administration.

PMID- 16982356
TI  - Heat stroke and multi-organ failure with liver involvement in an asylum-seeking
      refugee.
AB  - Heat stroke is the result of exposure to high environmental temperature and
      strenuous exercise representing a medical emergency characterized by an elevated
      core body temperature and central nervous system disorders. Slightly elevated
      liver enzymes, lacking clinical significance, seem to be frequent in heat stroke,
      whereas severe, clinically relevant, hepatocellular injury has been observed in
      only a minority of cases. In the present report we describe the case of an
      otherwise healthy young asylum-seeking refugee from East Timor, who developed
      severe heat stroke during his transportation to Greece in a closed container on a
      ship under unusually high temperatures. He was admitted to the hospital with
      severe multi-organ failure. After a short period of initial improvement, he
      developed severe hepatocellular injury and hepatic encephalopathy. Other causes
      of liver damage were excluded. The patient completely recovered.

PMID- 16982357
TI  - Occipital condyle fracture in a victim of a motor vehicle collision.
AB  - Occipital condyle fractures are rarely reported in the Emergency Medicine
      literature. It is unclear whether these fractures are rare or under-diagnosed.
      Occipital condyle fractures are associated with high-energy blunt trauma with
      significant cranial-cervical torque or axial loading. We report a case of a
      female patient with an occipital condyle fracture. The patient only complained of
      shoulder pain, but was found to have high cervical spine tenderness, after a
      moderate-speed front-end motor vehicle collision. Initial cervical spine
      radiographs were non-diagnostic. Computed tomography of the cervical spine
      demonstrated a non-displaced occipital condyle fracture. Conservative management
      with a semi-rigid cervical collar was successful in treating this patient's
      fracture. A review of the literature covers the diagnosis, radiographic findings,
      and management of this fracture.

PMID- 16982358
TI  - Southern Pacific Rattlesnake bite: a unique clinical challenge.
AB  - The Southern Pacific Coast Rattlesnake (Crotalus Helleri) is responsible for most
      of the snake bites in the coastal area of California from Los Angeles to San
      Diego. However, Crotalidae polyvalent immune ovine Fab fragments are not made
      from the venom of C. Helleri. This sheep-derived antivenom is indicated only in
      moderate snakebite envenomations. Very scant data are available regarding venom
      induced thrombocytopenia treated with ovine Crotaline Fab fragments. This is the
      second reported case of venom-induced thrombocytopenia that followed a "biphasic"
      pattern with the inability of ovine Crotaline Fab fragments to prevent this toxic
      effect. This case shows that severe envenomation from Crotalus Helleri associated
      with a delayed presentation to the Emergency Department does not have a sustained
      response to the ovine antivenom, and suggests that the use of Wyeth (equine)
      antivenom may be of greater therapeutic benefit.

PMID- 16982359
TI  - Isolated atomoxetine (Strattera) ingestions commonly result in toxicity.
AB  - Atomoxetine is a recently approved medication for attention deficit disorder. It
      is a selective norepinephrine reuptake inhibitor with an onset of action within 2
      h, and a duration of effect up to 40 h in therapeutic doses. Experience in the
      overdose setting is limited. After brief training in systematic chart review,
      reviewers blinded to the purpose of the study completed a standardized data
      collection sheet. Two years after atomoxetine was released, poison center patient
      encounters were reviewed. Age, outcomes, and signs and symptoms were recorded.
      All patients were followed until the cessation of symptoms or 24 h. Seventeen
      cases of isolated atomoxetine were reviewed. The age range of these 6 patients
      was 9 months to 28 years old with a mean of 15.6 years. The range of amount
      ingested was 10-1200 mg. The onset of symptoms was delayed as long as 3 h in 3
      patients. All neurological symptoms were preceded by tachycardia. Ten of 17
      patients had tachycardia, 6/17 had emesis, and 3/17 had agitation that required
      benzodiazepines to control. All symptoms resolved within 30 h. Supratherapeutic
      ingestions of atomoxetine can result in transient tachycardia, vomiting, and
      cognitive disturbances.

PMID- 16982360
TI  - Diffusion-weighted magnetic resonance imaging versus computed tomography in the
      diagnosis of acute ischemic stroke.
AB  - Current treatment protocols using reperfusion therapy for acute ischemic stroke
      rely on non-contrast computed tomography (NCCT), with most indications including
      the absence of acute hemorrhage or large volume of infarction in the presence of
      clinical signs and symptoms. This predictably results in a significant incidence
      of the administration of reperfusion therapy to patients with "stroke mimics,"
      such as migraine headache or Todd's paralysis after a seizure. Diffusion-weighted
      imaging (DWI) is a technique based on magnetic resonance imaging (MRI) that may
      be more sensitive and specific for acute cerebral ischemia than NCCT. In
      addition, data for techniques such as perfusion-weighted imaging can be acquired
      with minimal additional time required. This may allow better risk assessment of a
      clinical response to reperfusion therapy vs. the possibility of hemorrhagic
      complications. This article describes a methodical review of studies comparing
      the sensitivity, specificity, positive predictive value, and negative predictive
      value of DWI vs. NCCT in the evaluation of acute ischemic stroke. Data from
      studies meeting our screening criteria are combined to produce overall values for
      each.

PMID- 16982361
TI  - An unusual case of urinary retention in a competitive gymnast.
AB  - Hydrocolpos is the accumulation of blood behind an imperforate hymen. Patients
      often present in early adolescence with cyclic abdominal pain. We present the
      case of an elite gymnast who, after 6 months of symptoms and a series of
      incorrect diagnoses, was diagnosed with hydrocolpos. It is likely that the
      patient's extraordinary training regimen contributed to the difficulty in
      diagnosis.

PMID- 16982362
TI  - Effect of head rotation on vascular anatomy of the neck: an ultrasound study.
AB  - Carotid artery injury is a serious complication of landmark-guided internal
      jugular catheterization. Studies have determined that the internal jugular vein
      (IJV) frequently overlaps the carotid artery (CA), which has been postulated to
      increase the rate of arterial injury. The purpose of this study was to define the
      anatomic relationship of the IJV and CA by describing CA overlap by the more
      superficial IJV. We also seek to determine the effect of head rotation on the
      amount of overlap, which may have implications for IJV catheter placement. We
      prospectively studied the vascular anatomy of the neck in 156 Emergency
      Department patients. The primary intervention was head rotation to the left, as
      if the patient was positioned for right IJV catheterization. The patient's head
      was positioned at 0, 45 and 90 degrees of rotation. Ultrasound images were
      obtained in a transverse orientation. The percentage overlap of the CA by the IJV
      was measured. We also measured the distance between the jugular vein and the
      carotid artery. In neutral position, there was a mean overlap of 29% at the apex
      of the sternocleidomastoid. As the head was turned, the percent overlap
      increased. At 90 degrees, there was a mean overlap of 72%. Differences were
      determined to be significant by analysis of variance (ANOVA) with a p < 0.001.
      Furthermore, we found a distance of 10 mm between IJV and CA when the head is in
      neutral position. As the head was turned, the jugular-carotid distance decreased
      to 1 mm in the far lateral head position. These differences were also found to be
      significant by ANOVA with a p < 0.001. We concluded that the IJV overlaps the CA
      in the neutral position to a significant degree. This overlap increases until the
      head is fully turned, where most of the CA is overlapped by the IJV. This may
      help explain the mechanism of CA puncture. We propose two modifications to
      standard IJV line technique: minimize the patients' head rotation; and use
      ultrasound guidance for IJV catheterization.

PMID- 16982363
TI  - Bedside ultrasound of the soft tissue of the face: a case of early Ludwig's
      angina.
AB  - A case is reported of a 38-year-old man presenting with early Ludwig's angina. It
      is difficult to differentiate superficial from deep infections of the face and
      neck by physical examination alone. The diagnosis of this condition with bedside
      soft tissue ultrasound of the face is described. Ludwig's angina is an uncommon
      infection of the deep tissues of the face and neck that usually evolves from more
      superficial infections such as dental abscesses.

PMID- 16982364
TI  - Rash and fever.

PMID- 16982365
TI  - A rare abdominal complication of ventriculoperitoneal shunt.

PMID- 16982366
TI  - A case of carpometacarpal dislocation.

PMID- 16982367
TI  - Luxatio erecta: inferior humeral dislocation.

PMID- 16982368
TI  - Tetanus in an immunized, healthy adult.

PMID- 16982369
TI  - Re: Delayed ischemic stroke associated with methamphetamine use.

PMID- 16982370
TI  - Re: Journal club and teaching evidence-based medicine.

PMID- 16982373
TI  - Wireless handheld computers and voluntary utilization of computerized prescribing
      systems in the emergency department.
AB  - Illegible or invalid hand-written prescriptions can result in avoidable medical
      errors. Computer-based prescribing can mitigate the problem. An observational
      study was performed to examine the effect of wireless handheld computers
      (handhelds) on voluntary utilization of computerized prescribing within an
      Emergency Department. Handhelds with prescription-writing software were provided
      to physicians and the numbers of hand-written and computer-generated
      prescriptions were compared before and after the introduction of the handhelds.
      The resulting increase in computer-based prescribing was statistically
      significant and was observed largely among physicians who already used desktop
      computers for prescribing. The study concluded that handhelds increased voluntary
      utilization of computerized prescribing, but that the physicians most likely to
      use handhelds were those who already used desktop-based prescribing.

PMID- 16982374
TI  - The use of intramuscular benzodiazepines and antipsychotic agents in the
      treatment of acute agitation or violence in the emergency department.
AB  - The management of an agitated, abusive or violent patient is a common and
      challenging problem in Emergency Medicine. Priorities include measures to ensure
      the safety of the patient and the emergency staff, including provision of
      physical restraint of the patient and evaluation for correctable medical causes
      of such behavior. Medications used in the treatment of such patients include
      benzodiazepines and antipsychotic agents. The newer atypical antipsychotic agents
      seem to provide a safe and effective treatment for such patients. The atypical
      antipsychotic agents may have fewer short-term side effects than older typical
      antipsychotic agents, such as haloperidol and droperidol. Currently available
      atypical antipsychotic medications for the treatment of acute agitation include
      ziprasidone and olanzapine, which can be administered in an intramuscular
      formulation, and risperidone, which is available in a rapidly dissolvable tablet
      and liquid formulation.

PMID- 16982375
TI  - Injury pattern of the Flash-Ball, a less-lethal weapon used for law enforcement:
      report of two cases and review of the literature.
AB  - Less-lethal weapons are used in law enforcement to neutralize combative
      individuals and to disperse riot crowds. Local police recently used such an
      impact weapon, the Flash-Ball, in two different situations. This gun fires large
      rubber bullets with kinetic energies around 200 J. Although it is designed to
      avoid skin penetration, impacts at such energies may still create major trauma
      with associated severe injuries to internal organs. This is a report of 2
      patients shot with the Flash-Ball who required medical attention. One could be
      discharged quickly, but the other required hospitalization for heart and lung
      contusion. Both patients required advanced investigations including computed
      tomography (CT) scan. The medical literature on injuries induced by less-lethal
      impact weapons is reviewed. Impacts from the Flash-Ball can cause significant
      injury to internal organs, even without penetration. Investigations as for other
      high-energy blunt traumas are called for in these cases.

PMID- 16982376
TI  - Violence against emergency department workers.
AB  - The purpose of this study was to describe the violence experienced by Emergency
      Department (ED) workers from patients and visitors during the 6 months before the
      survey. Two hundred forty-two employees at five hospitals who came in direct
      contact with patients or visitors completed a survey. The study found that most
      workers had been verbally harassed by patients or visitors at least once. There
      were at least 319 assaults by patients and 10 assaults by visitors. Sixty-five
      percent of subjects assaulted stated that they did not report the assault to
      hospital authorities. Sixty-four percent of subjects had not had any violence
      prevention training during the previous 12 months. There were significant
      relationships among violent experiences, feelings of safety, and job
      satisfaction. ED workers are at high risk for violence, and efforts are needed to
      decrease the incidence of violence. Such efforts are likely to have a positive
      impact on job satisfaction and retention of ED workers.

PMID- 16982377
TI  - Media literacy has potential to improve adolescents' health.

PMID- 16982378
TI  - Vaccination: an opportunity to enhance early adolescent preventative services.
AB  - New vaccines are being developed that will be recommended for adolescents
      Adolescence is a time period when adolescent-parent dynamics change and when
      adolescents may be confronted with increasing opportunities to engage in risk
      taking behaviors such as sexual behavior and substance use. Despite clear
      recommendations regarding preventative counseling, many adolescents do not
      receive adequate preventive care. In this manuscript, we provide suggestions as
      to how a new vaccination schedule can be used to enhance preventative services to
      both adolescents and their parents.

PMID- 16982380
TI  - Time trends and demographic differences in youth exposure to alcohol advertising
      on television.
AB  - OBJECTIVE: To examine trends in youth exposure to alcohol advertising on
      television across different demographic groups. METHODS: We used television
      ratings data on alcohol advertisements to examine trends in exposure between
      September 1998 and February 2002. Further, we explored the differences in
      exposure across demographic groups by examining group-level alcohol ad exposure
      across specific networks, program types, and times of day. RESULTS: We found that
      boys were more exposed than girls and African-Americans are more exposed than
      whites. Moreover, the race differential appeared to be increasing over time,
      whereas the gender differential appeared to increase with age. Differences in
      viewing patterns across race and gender contributed to the observed differences
      in exposure to alcohol advertising on television. CONCLUSIONS: These results
      provide guidance in identifying comparative vulnerabilities in exposure to
      alcohol advertising on television, and can aid in the development of strategies
      to inoculate youth against those vulnerabilities.

PMID- 16982379
TI  - Association of cigarette smoking and media literacy about smoking among
      adolescents.
AB  - PURPOSE: To determine whether media literacy concerning tobacco use is
      independently associated with two clinically relevant outcome measures in
      adolescents: current smoking and susceptibility to smoking. METHODS: We asked
      high school students aged 14-18 years to complete a survey that included a
      validated 18-item smoking media literacy (SML) scale, items assessing current
      smoking and susceptibility to future smoking, and covariates shown to be related
      to smoking. We used logistic regression to assess independent associations
      between the two outcome measures and SML. RESULTS: Of the 1211 students who
      completed the survey, 19% reported current smoking. Controlling for all potential
      confounders of smoking, we found that an increase of one point (out of 10) in SML
      was independently associated with an odds ratio for smoking of .84 (95%
      confidence interval [CI] .71-.99). Compared with students below the median score
      on the SML scale, students above the median had an odds ratio for smoking of .57
      (95% CI .37-.87). Of the students who were nonsmokers, 40% were classified as
      susceptible to future smoking. Controlling for all potential confounders of
      smoking, we found that an increase of one point (out of 10) was independently
      associated with and an odds ratio for smoking susceptibility of .68 (95% CI .58
      .79). Compared with students below the median SML, students above the median SML
      had an odds ratio for smoking susceptibility of .49 (95% CI .35-.68).
      CONCLUSIONS: In this sample of high school students, higher SML is independently
      associated with reduced current smoking and reduced susceptibility to future
      smoking.

PMID- 16982381
TI  - Escalation and initiation of younger adolescents' substance use: the impact of
      perceived peer use.
AB  - PURPOSE: The middle school years are peak years for substance use initiation. The
      current study assessed the impact of peer influence on both initiation and
      escalation of cigarette, alcohol, and marijuana use among sixth, seventh, and
      eighth graders. METHODS: Youth (n = 974; 45% male) were surveyed twice over an
      academic year and reported on their personal substance use and their perception
      of peer substance use. The sample ranged in age from 10 to 15 years at Time 1 (M
      age = 11.95) and was 44% White, 26% Latino, 7% Asian American/Pacific Islander,
      4% African American, and 14% mixed ethnic origin. RESULTS: Hierarchical
      regressions examined whether personal and perceived peer substance use predicted
      later substance involvement, and logistic regressions assessed whether Time 1
      perceived peer and personal use of other substances discriminated between
      initiates and noninitiates. After controlling for personal substance use,
      perceived peer alcohol use predicted both increased alcohol and marijuana use,
      and perceived peer marijuana use predicted increased alcohol use. Only perceived
      peer alcohol use was associated with initiation of alcohol, and both perceived
      peer alcohol and marijuana use predicted onset of marijuana use. CONCLUSIONS:
      Results highlight the importance of perceived peer use in predicting both onset
      and escalation of use and suggest utilizing a multifaceted prevention approach
      that targets multiple substances.

PMID- 16982382
TI  - Are drug experimenters better adjusted than abstainers and users?: a longitudinal
      study of adolescent marijuana use.
AB  - PURPOSE: Experimentation with substance use is normative during adolescence and
      prior research suggests that adolescents who refrain from experimentation may be
      psychologically maladjusted. This longitudinal study compared lifetime marijuana
      abstainers (n = 1177), experimenters (n = 873), and frequent users (n = 205) at
      grade 12 on psychosocial functioning during late adolescence and young adulthood.
      METHODS: Participants were recruited from middle schools in 1985 (grade 7) and
      assessed repeatedly, including in 1990 (grade 12) and 1995 (age 23). Self-report
      surveys assessed lifetime substance use at grade 12, and psychosocial functioning
      at grade 12 and age 23. Group differences after controlling for key demographics
      were estimated using multivariate logistic regression and analysis of covariance.
      RESULTS: Adolescent abstainers from marijuana often fared better (and in no case
      worse) than experimenters and frequent users both concurrently and later in life
      on school engagement, family and peer relations, mental health, and deviant
      behavior. Similar results were found in ancillary analyses using a definition of
      adolescent "abstainer" that also accounted for cigarette and alcohol use.
      CONCLUSIONS: Results refute the idea that adolescents who abstain from substance
      use are maladjusted, and suggest instead that they function better than
      experimenters later in life, during the transition to young adulthood.

PMID- 16982383
TI  - Relationship of binge drinking and other health-compromising behaviors among
      urban adolescents in China.
AB  - PURPOSE: To describe frequency and patterns of alcohol use and explore the
      association between binge drinking and other health-compromising behaviors among
      adolescents in urban China. METHODS: Data on alcohol use and other behavioral
      risk factors were obtained from the 2004 China Adolescent Behavioral Risk Factor
      Survey conducted in 18 provincial capitals. Chi-square test was used to estimate
      the prevalence of alcohol use and compare differences in drinking frequency by
      gender, school type, and grade. Logistic regression was used to estimate the
      association between binge drinking and other health-compromising behaviors.
      RESULTS: Data were available on 54,040 students in grades 7 to 12. In all, 51.1%
      of students reported ever using alcohol (male: 58.6%; female: 44.3%), 29.7%
      reported drinking before 13 years of age, and 14.1% had gotten drunk at least
      once during the past year. In the 30 days preceding the interview, 25.2% students
      reported consuming at least one alcoholic drink (male: 31.4%; female: 19.6%) and
      10.3% reported at least one episode of binge drinking (male: 14.4%; female:
      6.6%). Male students from vocational senior high schools reported the highest
      frequency of alcohol use. The prevalence of other risk behaviors, such as
      smoking, drug use, and fighting were significantly higher among students with a
      positive history of binge drinking. CONCLUSIONS: Alcohol use among urban
      adolescents is a major problem in China. A comprehensive alcohol control policy
      is needed, incorporating measures to educate the public about the dangers of
      adolescent alcohol use and regulating access and purchase of alcohol by minors.

PMID- 16982384
TI  - Self-esteem in adolescent females.
AB  - PURPOSE: Self-esteem is a major "predictor" of satisfaction with life. This
      longitudinal study examined mean and individual changes in self-esteem, and how
      self-esteem is affected by race and body mass. METHODS: Girls were recruited at
      ages 9 and 10 years, and followed to age 22 years. The Harter Self-Perception
      Profile was administered every other year, analyzing scores from the Global Self
      Worth Scale, by age or developmental phase: ages 9-12 (I), 13-16 (II), and 17-22
      (III). Regression modeling included main effects and interactions between
      age/phase, race, and body mass index (BMI). RESULTS: Self-worth was greater in
      black than white women, and greater with lower BMI in both races. In the model
      with age ("traditional model") (with race and BMI), significant variables
      included BMI (inverse relationship) and the interactions between age and race,
      race and BMI, and the triple interaction between age, race, and BMI. In the model
      with phase ("transitional model") (with race and BMI), BMI, and the interactions
      between BMI and race, and race and phase, were significant. For example, self
      worth was generally lower in Phase II (middle adolescence) for white women. Self
      esteem tracked significantly (correlation 0.22, p < .001). An individual's self
      worth during any given phase of adolescence was correlated significantly with the
      other two phases. CONCLUSIONS: In this longitudinal analysis of self-esteem in
      adolescent girls, race and BMI are important predictors of self-esteem. Self
      esteem is consistent across the phases of adolescence, and comparable with other
      personality traits. As noted by others, lower levels of self-esteem may increase
      the vulnerability of adolescents to risky behaviors.

PMID- 16982385
TI  - Physical activity for bone health in inactive teenage girls: is a supervised,
      teacher-led program or self-led program best?
AB  - PURPOSE: To investigate the effect of a six-month teacher-led osteogenic physical
      activity program, vs. a self-led activity program, on ultrasound measurements of
      bone in inactive teenage girls. METHODS: Ninety sedentary girls [mean (SD) age
      16.3 (.6) years] were identified from 300 assessed for physical activity across
      five schools in southeast Ireland. Schools were matched and randomly assigned to
      a teacher-led physical activity (TLPA) program, a self-led physical activity
      (SLPA) program, or a control group. Broadband ultrasound attenuation (BUA), speed
      of sound (SOS), and os calcis stiffness index (OCSI) were measured using a
      portable ultrasound machine. Anthropometry, aerobic fitness, calcium intake, and
      physical activity were assessed, and focus groups held one month after program
      completion. Descriptive statistics, paired t-tests, and analysis of variance were
      used to analyze the data. RESULTS: Both intervention groups demonstrated
      significant improvements (p < .05) in BUA, SOS, OCSI and aerobic fitness, i.e.,
      TLPA: +14.9%, +21.9%, + 15.9%, and +8.5%, respectively, and SLPA: +10.6%, +30.3%,
      + 15.6%, and +5.1%, respectively, with no change in controls. Differences between
      intervention groups and controls were significant for BUA and OCSI (p < .05).
      TLPA and SLPA groups engaged in an average of 4.5 and 3.4 hours/week of physical
      activity, respectively, over the intervention period. The SLPA group continued to
      exercise after the intervention had ceased, whereas the TLPA group did not.
      CONCLUSIONS: Previously inactive teenage girls can adhere to an osteogenic
      activity program whether supervised or directing their own activity. Longer-term,
      sustainable initiatives with this age group are needed and might focus on
      developing personal skills for physical activity.

PMID- 16982386
TI  - The relationship between sedentary activities and physical inactivity among
      adolescents: results from the Canadian Community Health Survey.
AB  - PURPOSE: To evaluate the relationships between the time spent on sedentary
      activities (computer usage, video game playing, television viewing, and reading)
      and physical inactivity in a sample of youth (aged 12-19 years) from the 2000
      2001 Canadian Community Health Survey. METHODS: The study sample included 7982
      youth (4034 males, 3948 females) across Canada (mean age: 15.61 years, SD: 2.23
      years). Weekly time spent on computers, video games, television, and reading
      during leisure-time was obtained through self-reported questionnaires. Physical
      inactivity was determined by respondents' daily energy expenditure assessed
      through a physical activity questionnaire. Multivariate logistic regression
      analysis was conducted to examine the relationship between sedentary activities
      and physical inactivity respectively by gender. Sociodemographic variables,
      health status, and overweight status were controlled in the analysis. RESULTS: A
      substantial proportion of Canadian youth was inactive: 50.3% of males and 67.8%
      of females. Controlling for sociodemographic variables, health status, and body
      mass index, television viewing was significantly associated with physical
      inactivity for both males and females regardless of their overweight status.
      However, computer usage was associated with physical activity among males, and
      reading was associated with physical activity among females. CONCLUSIONS: There
      is a complex inter-relationship between sedentary behaviors and physical
      inactivity, highlighting the need for targeted interventions addressing patterns
      of sedentary behavior engagement. Reducing time spent on television viewing may
      be one plausible strategy within such interventions in reducing physical
      inactivity among youth.

PMID- 16982387
TI  - Sport participation and physical activity in adolescent females across a four
      year period.
AB  - PURPOSE: To determine the odds of engaging in future moderate-to-vigorous
      physical activity (MVPA) and vigorous physical activity (VPA) in adolescent
      female sport participants. A secondary purpose was to compare activity levels of
      three groups of girls, those who played sports at three time points, those who
      dropped out, and those who did not participate in sports. METHODS: Data were
      collected at three time points, eighth, ninth, and 12th grades, in 429 adolescent
      girls across the state of South Carolina. Demographic, sport participation and
      physical activity (PA) data were collected using surveys. Odds ratios were
      calculated to determine the association between sport participation and future PA
      behavior. PA was also compared for three sport participation groups
      (nonparticipants, dropouts, or three-year participants) using analysis of
      variance. RESULTS: For MVPA, ninth grade participants were more likely to be
      active in 12th grade (OR = 1.74 [1.13, 2.67]), and eighth and ninth grade
      participants more likely to be active in 12th grade than nonparticipants (OR =
      1.54 [confidence interval 1.01, 2.35]). For VPA, sport participants had higher
      odds of being active at all future time points. Three-year participants were
      significantly more vigorously active than nonparticipants and dropouts at all
      three time points (p < .01). CONCLUSIONS: Adolescent girls who participate in
      sports in eighth, ninth, and 12th grades are more likely to be vigorously active
      in 12th grade. These findings are novel in providing evidence that sport
      participation contributes to overall vigorous physical activity during late
      adolescence, when overall physical activity is known to decline precipitously.

PMID- 16982388
TI  - Impact of the "Planning to be Active" leisure time physical exercise program on
      rural high school students.
AB  - PURPOSE: The purpose of the study was to evaluate the effects of a Social
      Cognitive Theory-based intervention designed to increase the frequency of leisure
      time planned moderate and vigorous physical exercise among rural high school
      students attending physical education class. METHODS: Students in treatment and
      comparison groups were exposed to an activity-based physical education curricula.
      The treatment group received eight behavioral skill-building lessons integrated
      into the existing curriculum. RESULTS: The Social Cognitive Theory-based
      educational treatment increased levels of moderate physical exercise occurring
      outside the classroom. CONCLUSIONS: This study demonstrated an impact on
      adolescent leisure time moderate physical exercise using classroom instruction.
      The intervention was most effective with students who were previously sedentary.
      The curricular approaches used to promote regular moderate exercise may be useful
      for sedentary adolescents.

PMID- 16982389
TI  - Racial/ethnic and socioeconomic status differences in overweight and health
      related behaviors among American students: national trends 1986-2003.
AB  - PURPOSE: This article reports long-term trends by race/ethnicity and
      socioeconomic status (SES) in the percent of American students who are overweight
      and who engage in three health-related behaviors hypothesized to be associated
      with overweight. METHODS: Data are from the Monitoring the Future annual surveys,
      using nationally representative samples of eighth, 10th, and 12th grade students.
      Participants include 62,156 eighth and 64,899 10th graders who completed the 1993
      2003 surveys and 35,107 12th graders who completed the questionnaire form
      containing the measures pertaining to this study in the 1986-2003 surveys. Trends
      are presented separately by gender and grade level for different racial/ethnic
      and SES subgroups, in: (a) percent overweight (body mass index > or = 85th
      percentile), (b) percent who always or almost always eat breakfast, (c) percent
      who regularly exercise vigorously, and (d) average hours of weekday television
      viewing. RESULTS: The prevalence of overweight and of engaging in less healthy
      behaviors is considerably greater among youth from racial/ethnic minority
      backgrounds, of lower socioeconomic status, and in higher grades. Trends in
      overweight and these behaviors are found to vary substantially by gender,
      racial/ethnic group, socioeconomic status, and grade level. CONCLUSIONS: The
      study findings show well-established and persistent differences in the percent of
      racial/ethnic minority and low SES youth who are overweight and whose dietary and
      exercise habits are less healthy. Documentation of these problems may lead to
      research and policy agendas that will contribute both to our understanding and to
      the reduction of these important health disparities.

PMID- 16982390
TI  - Weight stereotypes and behavioral intentions toward thin and fat peers among
      White and Hispanic adolescents.
AB  - PURPOSE: This study examined weight stereotypes among White and Hispanic youth.
      Specific objectives were to: (a) document stereotyped beliefs about fat vs. thin
      peers; (b) examine the extent to which stereotyped beliefs contribute to
      behavioral intentions toward fat vs. thin peers; and (c) explore potential
      differences in weight stereotypes and behavioral intentions in White and Hispanic
      youth. METHODS: Participants, 157 Hispanic and 117 White middle school students,
      completed a demographic and background survey, the Fat Stereotypes Questionnaire
      (FSQ), Adjective Checklist, and Shared Activities Questionnaire (SAQ). RESULTS:
      Participants endorsed weight-related stereotypes, which were predictive of their
      social, academic, and recreation behavioral intentions. Participants indicated
      greater willingness to engage in social (p < .001), academic (p < .05), and
      recreational (p < .001) activities with thin vs. fat peers. Few differences were
      found between White and Hispanic adolescents. CONCLUSIONS: The results of this
      study highlight the ubiquitous nature of stereotyped beliefs about fat youth. Fat
      youth are considered unhealthy, lazy, and socially inept by their peers. Such
      stereotypes influence a variety of behavioral intentions and may contribute to
      discriminatory behaviors and difficult peer relationships. Additional research
      focused on weight stereotypes and peer relationships is needed.

PMID- 16982391
TI  - Long-term evaluation of multi-disciplinary treatment of morbid obesity in low
      income minority adolescents: La Rabida Children's Hospital's FitMatters program.
AB  - PURPOSE: Long-term evaluation of an empirically based program for the treatment
      of morbidly obese, low-income, minority adolescents. METHODS: In the first year,
      150 participants received cognitive-behavior therapy, nutritional education,
      medical monitoring, and structured exercise training. Weights and heights were
      collected at follow-up. Successful and Less Successful groups were delineated
      based on change in body mass index z-scores. Medical record review provided
      weight and height data one year before treatment for a subset of participants
      (comparison group). Analyses of variance examined differences between groups.
      Discriminant function analyses examined predictors of success in the domains of
      socioeconomic status, individual factors and psychological functioning, family
      factors, and prior weight loss behaviors. Correlates of success were explored.
      RESULTS: Eighty-three adolescents participated in the follow-up, on average 23
      months (SD = 3.8) after initial assessment. Nineteen (23%) participants achieved
      clinically meaningful weight change (-.70 z-scores or better). Discriminant
      function analyses, correlations, and direct comparisons showed that the
      Successful group, compared with the Less Successful group, on average, attended
      50% more sessions over 84% more weeks, were heavier initially, had somewhat
      better critical weight control skills (e.g., self-monitoring) before and during
      the program, and were somewhat more psychologically and intellectually challenged
      before treatment. CONCLUSION: Although some of these very high risk adolescents
      made clinically significant progress, more intensive treatments, like long-term
      residential treatments and bariatric surgery, may produce even more favorable
      outcomes.

PMID- 16982392
TI  - Large arterial elasticity varies as a function of gender and racism-related
      vigilance in black youth.
AB  - BACKGROUND: This exploratory study examined the relationship of gender and racism
      related vigilance to baseline and task-induced changes in large arterial
      elasticity (LAE). METHODS: The convenience sample consisted of 153 black youth (M
      age = 11.5 years, SD = 1.4) who were normotensive. Large arterial elasticity was
      measured via pulse wave contour analysis, before, during, and after a
      sequentially administered digit forward and digit backward task. Racism-related
      vigilance was reported by participants. RESULTS: Although findings from general
      linear models indicated that the independent effects of gender and racism-related
      vigilance were not significantly related to LAE (baseline, reactivity, or
      recovery) (all p > .05), these analyses showed that gender and racism-related
      vigilance interacted to predict baseline LAE (p < .02) and task-induced changes
      (reactivity only) in LAE (p < .006). Follow-up regression analyses explicating
      the pattern of these interaction effects indicated that 1) racism-related
      vigilance was marginally and inversely related to baseline LAE among boys (p <
      .06) but not in girls (p > .21); and, 2) racism-related vigilance was positively
      and significantly associated with task-induced changes (reactivity) in LAE among
      boys (p < .008) but not in girls (p > .30). CONCLUSIONS: The relationship between
      racism-related vigilance and LAE varies as a function of gender, and may have
      longer-term implications for between and within-group disparities in
      cardiovascular health.

PMID- 16982393
TI  - Do perceptions of friends' behaviors affect age at first sex? Evidence from Cebu,
      Philippines.
AB  - PURPOSE: To explore the effect of perceptions of friends' romantic and physical
      behaviors on adolescent sexual behavior and the relative influence of friends'
      sexual behaviors and maternal attitudes on age at first sex. METHODS: Using
      longitudinal data collected from 1943 adolescents who have never had sex at
      baseline in Cebu, Philippines, logistic regression assessed whether adolescents'
      perceptions of friends' sexual behaviors, measured at ages 14 to 16 years, were
      associated with age at first intercourse. Survival analysis assessed the hazard
      of having first intercourse by ages 17 to 19 years. Final models adjusted for
      sociodemographics, mothers'/caretakers' disapproval of premarital sex, living
      with a caretaker, and the adolescents' own behaviors at baseline. RESULTS: Boys
      and girls, who at ages 14 to 16 years, perceived that their friends had ever had
      boyfriends/girlfriends, dated, held hands, kissed, petted or had sex were
      significantly more likely to have experienced that behavior by ages 17 to 19
      years. For each additional behavior an adolescent perceived his or her friends to
      have experienced, the hazard of having sex at a younger age increased by 1.15 (p
      = .02) among boys and 1.19 (p < .002) among girls, after adjusting for
      mothers'/caretakers' disapproval of premarital sex and other factors.
      CONCLUSIONS: These results demonstrate the important role of peers in light of
      competing influences in adolescents' lives. They provide support for asking at
      early ages what romantic and physical behaviors adolescents think their friends
      have experienced. Interventions can use such information to better prepare
      adolescents to make responsible and informed decisions about sexuality.

PMID- 16982394
TI  - The role of parent religiosity in teens' transitions to sex and contraception.
AB  - PURPOSE: To examine whether multiple dimensions of parent and family religiosity-
      including parental religious attendance, denomination, beliefs, and family
      religious activities--are associated with the timing of sexual initiation or
      contraceptive use at first sex. METHODS: We analyze a sample of sexually
      inexperienced adolescents aged 12-14 years in the 1997 National Longitudinal
      Survey of Youth (NLSY97) to test the association between multiple dimensions of
      parent and family religiosity and the transition to first sexual experience and
      contraceptive use at first sex during the teen years. We assess the association
      between parent and family religiosity and the timing of adolescent sexual
      experience using multivariate event history models, and examine contraceptive use
      outcomes using logistic regressions. All analyses are conducted separately by
      gender and race/ethnicity. RESULTS: More frequent parental religious attendance
      is associated with a delayed timing of first sex among all sub-populations except
      among black adolescents. Engaging in family religious activities on a daily basis
      is associated with delayed sexual initiation among male, female, and white teens.
      Results for contraceptive use differ, however. Only strong parental religious
      beliefs and more frequent participation in family religious activities are
      associated with contraceptive use at first sex, in a negative direction, among
      males. CONCLUSION: More frequent parental religious attendance and family
      religious activities are related to later timing of sexual initiation,
      highlighting an important dimension of family environments that can help improve
      reproductive health outcomes for children. However, stronger family religiosity
      does not translate into improved contraceptive use.

PMID- 16982395
TI  - Having sex and condom use: potential risks and benefits reported by young,
      sexually inexperienced adolescents.
AB  - PURPOSE: This study determines what young adolescents themselves identify as the
      potential positive and negative outcomes of having sex, using a condom and not
      using a condom. METHODS: Using written surveys, 418 ethnically diverse ninth
      graders, 86% of whom had never had sex, responded to a scenario describing two
      adolescents who had sex. One randomly selected group read a scenario in which a
      condom was used; the other group read a scenario in which no condom was used. All
      participants were asked to list the risks and benefits of having sex. Depending
      on the scenario read, participants were asked to list the risks and benefits of
      either using or not using a condom. Responses were coded thematically.
      Percentages of responses were compared with chi-square analysis in total and by
      gender. RESULTS: Participants spontaneously identified a broad range of health
      and psychosocial risks and benefits of having sex, using a condom and not using a
      condom. A strong aversion to pregnancy was evident, and the risks of sexually
      transmitted disease/human immunodeficiency virus (STD/HIV) and condom malfunction
      were commonly mentioned. Benefits of using a condom included pregnancy and STD
      prevention. Benefits of both having sex and of not using a condom included
      improving the relationship, fun, and pleasure. Gender differences emerged across
      questions. CONCLUSIONS: Communication with adolescents regarding safe sexual
      activity could benefit from widening the communication from a focus on health
      risks to include discussion of the psychosocial risks and benefits that
      adolescents themselves think about with respect to sex and condom use.

PMID- 16982396
TI  - Validation of the European proxy KIDSCREEN-52 pilot test health-related quality
      of life questionnaire: first results.
AB  - PURPOSE: The KIDSCREEN project aims to develop a European cross-cultural generic
      self-administered Health-Related Quality of Life (HRQoL) instrument for children
      and adolescents. Proxy measures HRQoL should be a useful and practical
      alternative to assess children's HRQoL. The KIDSCREEN pilot study involved 3988
      children and 2526 child-proxy pairs in seven European countries (Austria,
      Switzerland, Germany, Spain, France, United Kingdom, and The Netherlands). The
      proxy instrument is based on the model developed from the children and
      adolescents reports. The aim of this study is to assess the psychometric
      properties of the proxy measure in terms of reliability and construct and
      external validity. METHODS: Confirmatory factor analysis (CFA) of the parent's
      data allows testing of the multidimensional structure of the proxy measure. Rasch
      analysis evaluates the scalability of each dimension. The mutltitrait-multimethod
      (MTMM) model assesses the trait validity through CFA. The agreement between
      children and proxies reports has been assessed using the Intraclass Correlation
      Coefficient (ICC). RESULTS: CFA indicates that the children's model is adequate
      to the parents' data. Reliability is satisfactory for every dimension (CFI =
      .957). For every dimension, Rasch analysis indicates that items form a
      unidimensional continuum. MTMM results confirm the trait validity of the
      instrument. Higher agreement was found for the physical well being dimension
      (ICC=.52) and school/cognitive functioning (ICC=.52). Adolescents showed higher
      agreement than the children, and girls higher than boys. Children with physical
      chronic health conditions showed higher agreement for several domains: physical
      and psychological well-being, social support, and school environment.
      CONCLUSIONS: Exploring different facets of validity showed satisfactory results.
      This new instrument provides a promising measure to further assess the
      relationships between youth and proxy reports.

PMID- 16982397
TI  - Factors associated with HIV infection in adolescent females in Zimbabwe.
AB  - PURPOSE: To identify factors associated with human immunodeficiency virus (HIV)
      infection among adolescent females in Zimbabwe and appropriate prevention
      strategies for this vulnerable population. METHODS: A total of 1807 females aged
      15-19 years completed a questionnaire and provided a blood sample for HIV testing
      as part of a nationally representative survey. Associations between HIV infection
      and factors operating at the individual, household, partner and community levels,
      as well as sexual behavior, were explored through bivariate and multivariate
      logistic regression analyses. Two multivariate models were fitted: the first
      model considered sexual risk behaviors and contextual variables, whereas the
      second model considered only contextual variables. RESULTS: Of 1807 adolescent
      females, 192 (10.6%) were HIV positive, and 41% of HIV-positive adolescent
      females reported no sexual risk behaviors. In the first multivariate model, the
      risk associated with number of lifetime sexual partners was increased for 1
      partner (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.57-3.6), 2
      partners (OR = 4.4, 95% CI = 2.22-8.55), and 3 or more partners (OR = 6.3, 95% CI
      = 2.56-15.7) as compared with having 0 partners. Believing that people with HIV
      have many sexual partners (OR = 1.71, 95% CI = 1.14-2.57) and that the man should
      take the initiative to have sex (OR = 1.55, 95% CI = 1.03-2.32) were also risk
      factors. In the second model, increased risk was associated with having ever
      married or lived with a man (OR = 1.99, 95% CI = 1.18-3.35) as well as the
      attitudes above. Decreased risk of HIV infection was associated with having a job
      (OR = .39, 95% CI = .18-.88), main activity in past 12 months was as a student
      (OR = .39, 95% CI = .19-.80), participation in school-based lectures on sexual
      health (OR = .49, 95% CI = .27-.87), and perceiving that AIDS is a somewhat
      serious problem in the community (OR = .55, 95% CI = .33-.92). CONCLUSIONS:
      Adolescent females in Zimbabwe who are married, not attending school and/or are
      unemployed, are at heightened risk for HIV infection. Interventions that improve
      their educational and employment opportunities, strengthen school-based
      prevention services, foster more equitable gender attitudes, and make marriage
      safer by, for example, promoting knowledge of partners' serostatus before
      marriage, may reduce their risk. Future research priorities are proposed.

PMID- 16982398
TI  - Risk factors for unintended versus intended rapid repeat pregnancies among
      adolescents.
AB  - PURPOSE: Whereas previous research has elucidated a number of risk factors for
      rapid repeat pregnancies among adolescents, we sought to assess both established
      and hypothetical risk factors in the context of the intendedness of the repeat
      pregnancy. METHODS: The study population, drawn from the 2002 National Survey of
      Family Growth (NSFG), consisting of women who experienced at least one pregnancy
      as an adolescent, were interviewed at least 24 months since that pregnancy's
      resolution and were aged 30 years and younger at the time of the NSFG interview.
      To evaluate the effect of various predictor variables on the intendedness of a
      rapid repeat pregnancy, we constructed a polytomous multiple logistic regression
      model. Outcomes are reported as ratios of odds ratios (ROR) and were calculated
      using women experiencing an adolescent pregnancy, but not a rapid repeat
      pregnancy, as the reference group. RESULTS: In the 2002 NSFG, 34% of the
      adolescents experiencing a rapid repeat pregnancy reported such pregnancies to be
      intended. Although young age (< or = 15 years) at first conception was associated
      with a decreased likelihood of an unintended rapid repeat pregnancy,
      racial/ethnic characteristics as well as characteristics of the teen's mother
      (educational status and young age of the teen's mother at first birth) were not
      associated with either intended or unintended rapid repeat pregnancies. Factors
      found to be associated with an increased likelihood of having an intended repeat
      pregnancy included an intended first pregnancy, prior poor obstetrical outcome,
      and having the repeat pregnancy intended by the teen's partner. Being married at
      the time of second conception was associated with a decreased likelihood of an
      unintended rapid repeat pregnancy. CONCLUSIONS: Consideration of the intendedness
      of repeat pregnancies among teenagers could help create more appropriate and
      effective family planning interventions.

PMID- 16982399
TI  - Screening emergency department patients for under-immunized adolescents.
AB  - Among 200 adolescents presenting to an emergency department in a city with high
      vaccination coverage, 11 (6%) were seronegative to rubella or varicella.
      Seronegative adolescents were older and more likely to be immigrants. ED
      screening for under-immunized adolescents may have a low yield in settings with
      high vaccine coverage.

PMID- 16982400
TI  - Depression, stress, and social support as predictors of high-risk sexual
      behaviors and STIs in young women.
AB  - A total of 403 women (aged 14-25 years) were surveyed to determine the
      association of psychosocial variables with risky sexual behaviors and sexually
      transmitted infections (STIs). Depression, stress, and low social support were
      associated with high-risk sexual behaviors and past STIs. When comparing
      adolescent women (aged 14-19) to young women (aged 20-25), the adolescents had
      stronger associations with the outcome variables.

PMID- 16982401
TI  - Injury trends for adolescents with early childhood lead exposure.
AB  - This pilot study investigated adolescents with well-documented childhood lead
      burdens to determine the relationship between lead and unintentional injury.
      Adolescents completed a self-administered injury questionnaire. Results
      demonstrated that elevated childhood blood lead concentrations were significantly
      related to injury variables. Further study is necessary to understand adolescent
      health and safety implications.

PMID- 16982402
TI  - Challenges of conducting a placebo-controlled trial for dysmenorrhea in
      adolescents.
AB  - We recruited adolescents to study oral contraceptives versus placebo for
      dysmenorrhea. We anticipated high discontinuation and concerns about safety, side
      effects, and sexual behavior. Treatment discontinuation (11%) and loss to follow
      up (1%) were lower than expected. The most common reason for nonenrollment was
      logistical issues (63%). Most participants remained abstinent.

PMID- 16982403
TI  - Lifetime community violence exposure and health risk behavior among young adults
      in college.
AB  - Among the undergraduates in this study, lifetime community violence exposure was
      associated with greater lifetime substance use and sexual risk-taking, and
      greater 30-day substance use and risky driving practices. Findings were
      independent of gender, ethnic minority status, personality characteristics,
      aggression, family socioeconomic status, family support, and neighborhood
      collective efficacy.

PMID- 16982404
TI  - Preferences of Israeli adolescents in regard to health services: a pilot study.
AB  - This pilot study surveyed Israeli adolescents' preferences regarding health
      services as a preliminary step for a national survey. A total of 444 students
      filled a questionnaire including demographics, personal health data, and
      preferences regarding 31 statements on health care, based on a Philadelphia
      questionnaire. Factors of most significant impact in seeking health care were
      cleanliness, integrity, respectfulness, knowledge, and competence. The 10 top
      statements important to Israeli teens included 9 of the 11 top statements of the
      Philadelphia teens. Future research may demonstrate change in outcome if
      adolescents' desires were attended based on a cultural adapted questionnaire.

PMID- 16982405
TI  - The "other side".

PMID- 16982407
TI  - Human papillomavirus (HPV) vaccine: a position statement of the Society for
      Adolescent Medicine.

PMID- 16982408
TI  - Cat and mouse.
AB  - The role of cathepsin B, a lysosomal protease implicated in amyloid-beta (Abeta1
      42) metabolism, in Alzheimer's disease remains controversial. In this issue of
      Neuron, Mueller-Steiner et al. manipulate the expression of cathepsin B in aged
      APP transgenic mice, observing that increased expression degrades preformed
      oligomeric and fibrillar amyloid, while inactivation accelerates beta
      amyloidosis.

PMID- 16982409
TI  - Inherited neuropathies: new genes don't fit old models.
AB  - Mutations in GARS cause dominantly inherited neuropathies in humans. GARS encodes
      glycyl-tRNA synthetase, the enzyme that couples glycine to its tRNA. In this
      issue of Neuron, Seburn et al. have identified and characterized a mutant mouse
      with a dominantly inherited axonal neuropathy caused by a Gars mutation that is
      inferred to have a gain of function.

PMID- 16982410
TI  - Nervous Rac: DOCK7 regulation of axon formation.
AB  - Microtubules play an important role in neuronal polarity. In this issue of
      Neuron, Watabe-Uchida et al. link a novel Rac-mediated pathway that regulates
      microtubule dynamics to axon formation.

PMID- 16982411
TI  - The synaptic vesicle cycle: is kissing overrated?
AB  - In this issue of Neuron, Granseth et al. re-examine the mechanism of endocytosis
      at hippocampal synapses using a new optical reporter, sypHy. They conclude that
      only a single slow mode of endocytosis operates at this synapse and that
      retrieval after physiological stimuli is largely, if not solely, dominated by the
      clathrin-mediated pathway. These conclusions dispute previous assertions that
      "kiss-and-run" is a major mechanism of vesicle recycling at hippocampal synapses.

PMID- 16982412
TI  - Leptin in energy balance and reward: two faces of the same coin?
AB  - Leptin receptors are expressed on mesolimbic dopamine neurons, yet little is
      known about the functional significance of this anatomical relationship. In this
      issue of Neuron, Hommel et al. reveal a novel site for leptin's regulation of
      feeding. In turn, Fulton et al. propose a novel role for leptin in regulating non
      feeding-related motivated behaviors.

PMID- 16982413
TI  - Multiple memory mechanisms in the cerebellum?
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are arguably two of
      the most widely discussed cellular plasticity mechanisms for learning and memory.
      However, the extent to which they are required for behavioral plasticity and
      learning is not clear. In this issue of Neuron, Boyden et al. use mice lacking
      CaMKIV and Hansel et al. use mice lacking alphaCaMKII to assess the contribution
      of LTD to cerebellar learning.

PMID- 16982414
TI  - From a whisper to a roar: adaptation to the mean and variance of naturalistic
      sounds.
AB  - In this issue of Neuron, Nagel and Doupe make a quantitative assessment of
      temporal adaptation in the avian auditory forebrain, capturing seemingly complex
      responses with a simple linear-nonlinear (LN) model of kinetics and gain. A
      comparison of these findings with similar results in the early visual system
      shows an important unifying picture of efficient sensory processing and
      adaptation.

PMID- 16982415
TI  - Neuronal RNA granules: movers and makers.
AB  - RNA localization contributes to cell polarity and synaptic plasticity. Evidence
      will be discussed that RNA transport and local translation in neurons may be more
      intimately linked than originally thought. Second, neuronal RNA granules,
      originally defined as intermediates involved in mRNA transport, are much more
      diverse in their composition and functions than previously anticipated. We focus
      on three classes of RNA granules that include transport RNPs, stress granules,
      and P bodies and discuss their potential functions in RNA localization, microRNA
      mediated translational regulation, and mRNA degradation.

PMID- 16982416
TI  - Thoughts for food: brain mechanisms and peripheral energy balance.
AB  - The past decade has witnessed dramatic advancements regarding the neuroendocrine
      control of food intake and energy homeostasis and the effects of peripheral
      metabolic signals on the brain. The development of molecular and genetic tools to
      visualize and selectively manipulate components of homeostatic systems, in
      combination with well-established neuroanatomical, electrophysiological,
      behavioral, and pharmacological techniques, are beginning to provide a clearer
      picture of the intricate circuits and mechanisms of these complex processes. In
      this review, we attempt to provide some highlights of these advancements and
      pinpoint some of the shortcomings of the current understanding of the brain's
      involvement in the regulation of daily energy homeostasis.

PMID- 16982417
TI  - Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) may result from the accumulation of amyloid-beta (Abeta)
      peptides in the brain. The cysteine protease cathepsin B (CatB) is associated
      with amyloid plaques in AD brains and has been suspected to increase Abeta
      production. Here, we demonstrate that CatB actually reduces levels of Abeta
      peptides, especially the aggregation-prone species Abeta1-42, through proteolytic
      cleavage. Genetic inactivation of CatB in mice with neuronal expression of
      familial AD-mutant human amyloid precursor protein (hAPP) increased the relative
      abundance of Abeta1-42, worsening plaque deposition and other AD-related
      pathologies. Lentivirus-mediated expression of CatB in aged hAPP mice reduced
      preexisting amyloid deposits, even thioflavin S-positive plaques. Under cell-free
      conditions, CatB effectively cleaved Abeta1-42, generating C-terminally truncated
      Abeta peptides that are less amyloidogenic. Thus, CatB likely fulfills
      antiamyloidogenic and neuroprotective functions. Insufficient CatB activity might
      promote AD; increasing CatB activity could counteract the neuropathology of this
      disease.

PMID- 16982418
TI  - An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a
      Charcot-Marie-Tooth 2D mouse model.
AB  - Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D
      (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl
      tRNA synthetase (GlyRS). Here we report a dominant mutation in Gars that causes
      neuropathy in the mouse. Importantly, both sensory and motor axons are affected,
      and the dominant phenotype is not caused by a loss of the GlyRS aminoacylation
      function. Mutant mice have abnormal neuromuscular junction morphology and
      impaired transmission, reduced nerve conduction velocities, and a loss of large
      diameter peripheral axons, without defects in myelination. The mutant GlyRS
      enzyme retains aminoacylation activity, and a loss-of-function allele, generated
      by a gene-trap insertion, shows no dominant phenotype in mice. These results
      indicate that the CMT2D phenotype is caused not by reduction of the canonical
      GlyRS activity and insufficiencies in protein synthesis, but instead by novel
      pathogenic roles for the mutant GlyRS that specifically affect peripheral
      neurons.

PMID- 16982419
TI  - The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation
      of stathmin/Op18.
AB  - The polarization of a neuron generally results in the formation of one axon and
      multiple dendrites, allowing for the establishment of neuronal circuitry. The
      molecular mechanisms involved in priming one neurite to become the axon,
      particularly those regulating the microtubule network, remain elusive. Here we
      report the identification of DOCK7, a member of the DOCK180-related protein
      superfamily, as a Rac GTPase activator that is asymmetrically distributed in
      unpolarized hippocampal neurons and selectively expressed in the axon. Knockdown
      of DOCK7 expression prevents axon formation, whereas overexpression induces
      formation of multiple axons. We further demonstrate that DOCK7 and Rac activation
      lead to phosphorylation and inactivation of the microtubule destabilizing protein
      stathmin/Op18 in the nascent axon and that this event is important for axon
      development. Our findings unveil a pathway linking the Rac activator DOCK7 to a
      microtubule regulatory protein and highlight the contribution of microtubule
      network regulation to axon development.

PMID- 16982420
TI  - Neuroligins determine synapse maturation and function.
AB  - Synaptogenesis, the generation and maturation of functional synapses between
      nerve cells, is an essential step in the development of neuronal networks in the
      brain. It is thought to be triggered by members of the neuroligin family of
      postsynaptic cell adhesion proteins, which may form transsynaptic contacts with
      presynaptic alpha- and beta-neurexins and have been implicated in the etiology of
      autism. We show that deletion mutant mice lacking neuroligin expression die
      shortly after birth due to respiratory failure. This respiratory failure is a
      consequence of reduced GABAergic/glycinergic and glutamatergic synaptic
      transmission and network activity in brainstem centers that control respiration.
      However, the density of synaptic contacts is not altered in neuroligin-deficient
      brains and cultured neurons. Our data show that neuroligins are required for
      proper synapse maturation and brain function, but not for the initial formation
      of synaptic contacts.

PMID- 16982421
TI  - Modulation of inactivation properties of CaV2.2 channels by 14-3-3 proteins.
AB  - Inactivation of presynaptic Ca(V)2.2 channels may play a role in regulating short
      term synaptic plasticity. Here, we report a direct modulation of Ca(V)2.2 channel
      inactivation properties by 14-3-3, a family of signaling proteins involved in a
      wide range of biological processes. The structural elements critical for 14-3-3
      binding and channel modulation lie in the carboxyl tail of the pore-forming
      alpha(1B) subunit, where we have identified two putative 14-3-3 interaction
      sites, including a phosphoserine-containing motif that directly binds to 14-3-3
      and a second region near the EF hand and IQ domain. In transfected tsA 201 cells,
      14-3-3 coexpression dramatically slows open-state inactivation and reduces
      cumulative inactivation of Ca(V)2.2 channels. In hippocampal neurons,
      interference with 14-3-3 binding accelerates Ca(V)2.2 channel inactivation and
      enhances short-term synaptic depression. These results demonstrate that 14-3-3
      proteins are important regulators of Ca(V)2.2 channel activities and through this
      mechanism may contribute to their regulation of synaptic transmission and
      plasticity.

PMID- 16982422
TI  - Clathrin-mediated endocytosis is the dominant mechanism of vesicle retrieval at
      hippocampal synapses.
AB  - The maintenance of synaptic transmission requires that vesicles be recycled after
      releasing neurotransmitter. Several modes of retrieval have been proposed to
      operate at small synaptic terminals of central neurons, including a fast "kiss
      and-run" mechanism that releases neurotransmitter through a fusion pore. Using an
      improved fluorescent reporter comprising pHluorin fused to synaptophysin, we find
      that only a slow mode of endocytosis (tau = 15 s) operates at hippocampal
      synapses when vesicle fusion is triggered by a single nerve impulse or short
      burst. This retrieval mechanism is blocked by overexpression of the C-terminal
      fragment of AP180 or by knockdown of clathrin using RNAi, and it is associated
      with the movement of clathrin and vesicle proteins out of the synapse. These
      results indicate that clathrin-mediated endocytosis is the major, if not
      exclusive, mechanism of vesicle retrieval after physiological stimuli.

PMID- 16982423
TI  - The synaptic mechanism of direction selectivity in distal processes of starburst
      amacrine cells.
AB  - Patch-clamp recordings revealed that distal processes of starburst amacrine cells
      (SACs) received largely excitatory synaptic input from the receptive field center
      and nearly purely inhibitory inputs from the surround during both stationary and
      moving light stimulations. The direct surround inhibition was mediated mainly by
      reciprocal GABA(A) synapses between opposing SACs, which provided leading and
      prolonged inhibition during centripetal stimulus motion. Simultaneous Ca(2+)
      imaging and current-clamp recording during apparent-motion stimulation further
      demonstrated the contributions of both centrifugal excitation and GABA(A/C)
      receptor-mediated centripetal inhibition to the direction-selective Ca(2+)
      responses in SAC distal processes. Thus, by placing GABA release sites in
      electrotonically semi-isolated distal processes and endowing these sites with
      reciprocal GABA(A) synapses, SACs use a radial-symmetric center-surround
      receptive field structure to build a polar-asymmetric circuitry. This circuitry
      may integrate at least three levels of interactions--center excitation, surround
      inhibition, and reciprocal inhibitions that amplify the center--surround
      antagonism-to generate robust direction selectivity in the distal processes.

PMID- 16982424
TI  - Leptin receptor signaling in midbrain dopamine neurons regulates feeding.
AB  - The leptin hormone is critical for normal food intake and metabolism. While
      leptin receptor (Lepr) function has been well studied in the hypothalamus, the
      functional relevance of Lepr expression in the ventral tegmental area (VTA) has
      not been investigated. The VTA contains dopamine neurons that are important in
      modulating motivated behavior, addiction, and reward. Here, we show that VTA
      dopamine neurons express Lepr mRNA and respond to leptin with activation of an
      intracellular JAK-STAT pathway and a reduction in firing rate. Direct
      administration of leptin to the VTA caused decreased food intake while long-term
      RNAi-mediated knockdown of Lepr in the VTA led to increased food intake,
      locomotor activity, and sensitivity to highly palatable food. These data support
      a critical role for VTA Lepr in regulating feeding behavior and provide
      functional evidence for direct action of a peripheral metabolic signal on VTA
      dopamine neurons.

PMID- 16982425
TI  - Leptin regulation of the mesoaccumbens dopamine pathway.
AB  - Leptin is an adipose-derived hormone that acts on hypothalamic leptin receptors
      to regulate energy balance. Leptin receptors are also expressed in
      extrahypothalamic sites including the ventral tegmental area (VTA), critical to
      brain reward circuitry. We report that leptin targets DA and GABA neurons of the
      VTA, inducing phosphorylation of signal-transducer-and-activator-of-transcription
      3 (STAT3). Retrograde tracing combined with pSTAT3 immunohistochemistry show
      leptin-responsive VTA neurons projecting to nucleus accumbens (NAc). Assessing
      leptin function in the VTA, we showed that ob/ob mice had diminished locomotor
      response to amphetamine and lacked locomotor sensitization to repeated
      amphetamine injections, both defects reversed by leptin infusion. Electrically
      stimulated DA release from NAc shell terminals was markedly reduced in ob/ob
      slice preparations, and NAc DA levels and TH expression were lower. These data
      define a role for leptin in mesoaccumbens DA signaling and indicate that the
      mesoaccumbens DA pathway, critical to integrating motivated behavior, responds to
      this adipose-derived signal.

PMID- 16982426
TI  - Selective engagement of plasticity mechanisms for motor memory storage.
AB  - The number and diversity of plasticity mechanisms in the brain raises a central
      question: does a neural circuit store all memories by stereotyped application of
      the available plasticity mechanisms, or can subsets of these mechanisms be
      selectively engaged for specific memories? The uniform architecture of the
      cerebellum has inspired the idea that plasticity mechanisms like cerebellar long
      term depression (LTD) contribute universally to memory storage. To test this
      idea, we investigated a set of closely related, cerebellum-dependent motor
      memories. In mutant mice lacking Ca(2+)/calmodulin-dependent protein kinase IV
      (CaMKIV), the maintenance of cerebellar LTD is abolished. Although memory for an
      increase in the gain of the vestibulo-ocular reflex (VOR) induced with high
      frequency stimuli was impaired in these mice, memories for decreases in VOR gain
      and increases in gain induced with low-frequency stimuli were intact. Thus, a
      particular plasticity mechanism need not support all cerebellum-dependent
      memories, but can be engaged selectively according to the parameters of training.

PMID- 16982427
TI  - alphaCaMKII Is essential for cerebellar LTD and motor learning.
AB  - Activation of postsynaptic alpha-calcium/calmodulin-dependent protein kinase II
      (alphaCaMKII) by calcium influx is a prerequisite for the induction of long-term
      potentiation (LTP) at most excitatory synapses in the hippocampus and cortex.
      Here we show that postsynaptic LTP is unaffected at parallel fiber-Purkinje cell
      synapses in the cerebellum of alphaCaMKII(-/-) mice. In contrast, a long-term
      depression (LTD) protocol resulted in only transient depression in juvenile
      alphaCaMKII(-/-) mutants and in robust potentiation in adult mutants. This
      suggests that the function of alphaCaMKII in parallel fiber-Purkinje cell
      plasticity is opposite to its function at excitatory hippocampal and cortical
      synapses. Furthermore, alphaCaMKII(-/-) mice showed impaired gain-increase
      adaptation of both the vestibular ocular reflex and optokinetic reflex. Since
      Purkinje cells are the only cells in the cerebellum that express alphaCaMKII, our
      data suggest that an impairment of parallel fiber LTD, while leaving LTP intact,
      is sufficient to disrupt this form of cerebellar learning.

PMID- 16982428
TI  - Temporal processing and adaptation in the songbird auditory forebrain.
AB  - Songbird auditory neurons must encode the dynamics of natural sounds at many
      volumes. We investigated how neural coding depends on the distribution of
      stimulus intensities. Using reverse-correlation, we modeled responses to
      amplitude-modulated sounds as the output of a linear filter and a nonlinear gain
      function, then asked how filters and nonlinearities depend on the stimulus mean
      and variance. Filter shape depended strongly on mean amplitude (volume): at low
      mean, most neurons integrated sound over many milliseconds, while at high mean,
      neurons responded more to local changes in amplitude. Increasing the variance
      (contrast) of amplitude modulations had less effect on filter shape but decreased
      the gain of firing in most cells. Both filter and gain changes occurred rapidly
      after a change in statistics, suggesting that they represent nonlinearities in
      processing. These changes may permit neurons to signal effectively over a wider
      dynamic range and are reminiscent of findings in other sensory systems.

PMID- 16982429
TI  - Influences of rewarding and aversive outcomes on activity in macaque lateral
      prefrontal cortex.
AB  - Both appetitive and aversive outcomes can reinforce animal behavior. It is not
      clear, however, whether the opposing kinds of reinforcers are processed by
      specific or common neural mechanisms. To investigate this issue, we studied
      macaque monkeys that performed a memory-guided saccade task for three different
      outcomes, namely delivery of liquid reward, avoidance of air puff, and feedback
      sound only. Animals performed the task best in rewarded trials, intermediately in
      aversive trials, and worst in sound-only trials. Most task-related activity in
      lateral prefrontal cortex was differentially influenced by the reinforcers.
      Aversive avoidance had clear effects on some prefrontal neurons, although the
      effects of rewards were more common. We also observed neurons modulated by both
      positive and negative reinforcers, reflecting reinforcement or attentional
      processes. Our results demonstrate that information about positive and negative
      reinforcers is processed differentially in prefrontal cortex, which could
      contribute to the role of this structure in goal-directed behavior.

PMID- 16982430
TI  - Resolving emotional conflict: a role for the rostral anterior cingulate cortex in
      modulating activity in the amygdala.
AB  - Effective mental functioning requires that cognition be protected from emotional
      conflict due to interference by task-irrelevant emotionally salient stimuli. The
      neural mechanisms by which the brain detects and resolves emotional conflict are
      still largely unknown, however. Drawing on the classic Stroop conflict task, we
      developed a protocol that allowed us to dissociate the generation and monitoring
      of emotional conflict from its resolution. Using functional magnetic resonance
      imaging (fMRI), we find that activity in the amygdala and dorsomedial and
      dorsolateral prefrontal cortices reflects the amount of emotional conflict. By
      contrast, the resolution of emotional conflict is associated with activation of
      the rostral anterior cingulate cortex. Activation of the rostral cingulate is
      predicted by the amount of previous-trial conflict-related neural activity and is
      accompanied by a simultaneous and correlated reduction of amygdalar activity.
      These data suggest that emotional conflict is resolved through top-down
      inhibition of amygdalar activity by the rostral cingulate cortex.

PMID- 16982431
TI  - Prokaryotic expression, purification and activity assay of recombinant vascular
      endothelial growth factor.
AB  - OBJECTIVE: To express human vascular endothelial growth factor (hVEGF(165)) in E.
      coli JM109 in the form of fusion protein by genetic engineering and test the
      biological activity and immunological competence of the expressed protein.
      METHODS: hVEGF(165) gene was subcloned by PCR and inserted into pQE30 plasmid.
      hVEGF(165) fusion protein was expressed in E. coli JM109 and purified by Ni(2+)
      NTA. The immunological competence of the expressed protein was tested by means of
      Western blotting and enzyme-linked immunosorbent assay (ELISA), and its
      biological activity was assayed by chicken chorioallantoic membrane (CAM) and
      Matrigel angiogenesis assay. RESULTS: The recombinant hVEGF(165) fusion protein
      was successfully expressed in E. coli JM109 and its expression accounted for 30%
      of the total cellular protein. The purified protein presented a single band of 23
      kD in SDS-PAGE. Western blotting, ELISA, CAM and matrigel angiogenesis assay
      showed excellent immunologic competence and biological activity of the
      recombinant protein. CONCLUSION: Recombinant hVEGF(165) protein with excellent
      biological activity has been successfully expressed in E.coli JM109, which may
      facilitate future study in construction of prefabricated tissue-engineered bone
      graft.

PMID- 16982432
TI  - [Modulation of inflammatory cytokines by ATP-binding cassette A1 in THP-1
      macrophages].
AB  - OBJECTIVE: To observe the effects of ATP-binding cassette A1 (ABCA1) on
      intercellular cell adhesion molecule type 1 (ICAM-1), monocyte chemoattractant
      protein-1 (MCP-1) and interleukin-1beta (IL-1beta) in THP-1 macrophages
      stimulated with 8-Br-cAMP to identify a possible new mechanism that ABCA1
      contributes to atherosclerogenesis (AS). METHODS: Monocytic THP-1 cells were
      cultured in the presence of 100 nmol/L phorbol myristate acetate (PMA) for 72 h
      to transform the cells into THP-1 macrophages. After the macrophages were
      stimulated with 8-Br-cAMP (final concentration 0.5 mmol/L) for 3, 6, 12 and 24 h
      respectively, the amounts of ABCA1, ICAM-1 and MCP-1 mRNA were examined by real
      time fluorescent quantitative RT-PCR, and the protein amounts of ABCA1, ICAM-1,
      MCP-1 and IL-1beta were determined by Western blotting and enzyme-linked
      immunosorbent assay (ELISA). Phosphorothioate antisense oligonucleotides of ABCA1
      were add into the culture media at a final concentration of 100 nmol/L and the
      experiments were repeated. RESULTS: ABCA1, ICAM-1 and MCP-1 mRNA and protein and
      IL-1beta protein were increased in the macrophages after stimulation with 8-Br
      cAMP for 6 and 12 h. The mRNA expressions of ABCA1, ICAM-1 and MCP-1 were
      decreased significantly at 3 and 6 h (P<0.01), and the protein expressions of
      ABCA1, ICAM-1, MCP-1 and IL-1beta declined significantly at 12 and 24 h (P<0.01)
      after transfection of the macrophages with antisense oligonucleotides of ABCA1.
      CONCLUSION: ABCA1 can increase the expressions of the inflammatory cytokines in
      THP-1 macrophages stimulated by 8-Br-cAMP and plays a role in the pathogenesis of
      AS.

PMID- 16982433
TI  - [Effects of pentobarbital sodium on rhythmical respiration of neonatal rat
      medullary preparations].
AB  - OBJECTIVE: To study the effects of pentobarbital sodium in generation and
      modulation of rhythmical respiration in neonatal rats. METHODS: The effects of
      pentobarbital sodium were examined on hypoglossal nerve (XII) rootlets and
      inspiratory neurons in the medullary preparations including the medial region of
      the nucleus retrofacialis, pre-Botzinger complex and the dorsal respiratory group
      of neonatal rats aged 0-3 days. The electrical activity of XII nerve rootlets and
      inspiratory neurons were recorded. Different doses of pentobarbital sodium (20,
      40, 60, 80 micromol/L) were added into modified Krebs solution to observe changes
      in the discharge activity of XII nerve and inspiratory neurons. Bicuculline was
      used to further investigate the mechanisms that pentobarbital sodium suppresses
      respiration. RESULTS: The discharge activity inhibition of XII nerve was
      increased as pentobarbital sodium doses increased from 20 to 60 micromol/L, but
      no significant difference was observed between the doses of 60 and 80 micromol/L.
      Bicuculline can partly restore the rhythmical respiration discharge activity.
      CONCLUSION: Pentobarbital sodium can suppress respiration partly via GABAA
      receptors.

PMID- 16982434
TI  - [Effects of peritoneal dialysis solution on proliferation and apoptosis of rat
      peritoneal mesothelial cells].
AB  - OBJECTIVE: To investigate the effects of peritoneal dialysis solution (PDS) on
      proliferation and apoptosis of rat peritoneal mesothelial cells (RPMCs). METHODS:
      The proliferation of RPMCs treated with PDS containing glucose of different
      concentrations for different times in vitro were examined by MTT colorimeric
      assay. The cell cycles and cell apoptosis rate were determined by flow cytometry.
      RESULTS: After PDS treatment for 1 h, the cell proliferation inhibition rate,
      percentage of cells at G(0)/G(1) stage and early cell apoptosis rate increased,
      and such increment was more manifest with higher glucose concentration in PDS and
      longer treatment time of the cells. After treatment with PDS containing 4.25%
      glucose for 3 h, the proliferation inhibition rate of the RPMCs reached 44.12%,
      the percentage of cells at the G(0)/G(1) stage amounted to 71.95% and the early
      apoptosis rate reached 23.59%, which was several times higher than that of the
      negative control and 1.5% glucose/PDS groups, and also higher than that of 4.25%
      mannitol/PDS groups. CONCLUSION: PDS containing high-concentration glucose can
      induce significant apoptosis and inhibit the proliferation of RPMCs in vitro.

PMID- 16982435
TI  - [Construction of Lactococcus lactis expression vector of recombinant human
      trefoil factor family 2].
AB  - OBJECTIVE: To construct a Lactococcus lactis expression vector of c-myc-tagged
      human trefoil factor family 2 (hTFF2) fusion gene to prepare for genetic
      modification of Lactococcus lactis that can secrete bioactive c-myc-hTFF2
      protein. METHODS: Based on the amino sequence of hTFF2 and optimal Lactococcus
      lactis codon usage, the cDNA of hTFF2 was designed and extended at their 5' ends
      with a sequence encoding c-myc as the molecular tag. According to the restriction
      sites of pBluescript II sk (+), the SalI and BamHI sites were arranged at the 5'
      and 3' ends of the fusion gene respectively. The sequence of the fusion gene c
      myc-hTFF2 was designed as 14 oligonucleotides that overlapped with each other,
      and by means of PCR, all the oligonucleotides were spliced to complete the
      construction of c-myc-hTFF2 fusion gene. The target gene of c-myc-hTFF2 was
      inserted into pBluescript II sk (+) to construct the cloning vector pBS-hTFF2 of
      c-myc-hTFF2 followed by verification by enzyme digestion and DNA sequencing. By
      digestion of pBS-TFF2 with BamHI/SalI and of pNBC1000 with BamHI/XhoI, we
      connected c-myc-hTFF2 with pNBC1000 to construct the expression vector c-myc
      hTFF2 in E. coli named as pNTFF2. After digestion of pNTFF2 and pTRKH2 with XbaI,
      the target gene was subcloned into pTRKH2 and the construction of the expression
      vector pTRTFF2 in Lactococcus lactis was completed. The constructed vector was
      identified by restriction enzyme digestion. RESULTS AND CONCLUSION: The
      expression vector pTRTFF2 of c-myc-hTFF2 fusion gene has been successfully
      constructed. Assembly of oligonucleotides in vitro is an effective means to
      synthesize the target fusion gene and this prepares the ground for constructing
      engineered bacterium of Lactococcus lactis.

PMID- 16982436
TI  - [Effect of histamine on intracortical blood vessels of rats].
AB  - OBJECTIVE: To investigate histamine-induced changes of the intracortical vessels
      in the cortical slice of rat brain. METHODS: Immunohistochemistry was employed to
      detect the expression of H1 and H2 receptors in the intracortical blood vessels
      of rats. Histamine-induced constriction of the intracortical blood vessels of the
      brain slices was observed with differential interference contrast microscope.
      Measurements of the luminal diameter were made on-line during the course of the
      experiment and confirmed off-line from the stored images. In order to observe
      whether histamine H1 and H2 receptors affected histamine-induced constriction,
      the intracortical blood vessels in the brain slices were pre-treated with H1
      receptor antagonist diphenhydramine and H2 receptor antagonist cimetidine.
      RESULTS: Expression of H1 and H2 receptors was detected in the intracortical
      blood vessels of the rat brain. Histamine (1-100 micromol/L) induced a
      concentration-dependent constriction from (1.48-/+0.67)% to (32.91-/+7.91)%. The
      reactions to each histamine concentration were significantly (P<0.01) different
      from each other, with the exception of the highest histamine concentrations (30
      and 100 micromol/L) when maximal constriction due to histamine were observed
      (P>0.05). With pre-treatment of the slice with 10 micromol/L diphenhydramine,
      application of histamine did not elicit constriction. Pre-treatment of the slice
      with 10 micromol/L cimetidine did not completely inhibit but somehow
      significantly weakened vascular constriction in response to histamine treatment
      at 10 and 30 micromol/L (P<0.05). CONCLUSION: Histamine can induce constriction
      of the intracortical blood vessels, which is mediated by H1 receptor.

PMID- 16982437
TI  - [Effects of prenatal stress on kinetic properties of high-voltage-activated Ca2+
      channel in freshly isolated offspring rat hippocampal CA3 pyramidal neurons].
AB  - OBJECTIVE: To investigate the effects of prenatal stress (PNS) on kinetic
      properties of high-voltage-activated (HVA) Ca(2+) channel in freshly isolated
      offspring rat hippocampal CA3 pyramidal neurons. METHODS: The pregnant rats were
      exposed to restraint stress, and the hippocampal CA3 pyramidal neurons were
      freshly isolated from the offspring rats to record voltage-gate Ca(2+) channel
      currents in these neurons using whole-cell configuration of patch-clamp
      technique. RESULTS: PNS significantly increased HVA calcium current density and
      integral current but did not alter the steady-state activation and steady-state
      inactivation properties of HVA Ca(2+) channel in the offspring rat CA3 neurons.
      The maximal HVA calcium current density was -40.89-/+0.31 pA/pF in the control
      group (n=10) and -49.44-/+0.37 pA/pF in PNS group (n=8, P<0.01). The maximal
      integral current of the HVA Ca(2+) channel was 106.81-/+4.20 nA*ms in the control
      group (n=10) and 133.49-/+2.59 nA*ms in the PNS group (n=8, P<0.01). CONCLUSION:
      Maternal exposure to stress during the critical phase of pregnancy may result in
      long-lasting effects on the ion channels of the hippocampal neurons in the
      offspring rats.

PMID- 16982438
TI  - [In vitro screening of 32 traditional Chinese herbal extracts against U2OS human
      osteosarcoma cells].
AB  - OBJECTIVE: To test 32 traditional Chinese medicinal herbs with effects against
      osteosarcoma in vitro. METHODS: U(2)OS human osteosarcoma cell line was treated
      with the extracts of the Chinese herbs at various concentrations. The changes in
      cell proliferation in response to the treatment were examined by MTT assay, and
      the effects of these extracts against human osteosarcoma growth were compared.
      Morphological observation, flow cytometry and Annexin V were employed to detect
      the cell apoptosis after the treatments. RESULTS: According to the results of MTT
      assay, several of the 32 Chinese herbs, especially Venenum Bufonis and oxgall
      powder, were identified to produce growth inhibition against U(2)OS cells.
      Further study of the aqueous extracts of Venenum Bufonis and oxgall powder
      demonstrated their effects in inducing U(2)OS cell apoptosis, and Venenum Bufonis
      showed the strongest effect. In spite of the obvious growth inhibitory effect of
      oxgall powder, its extract induced cell apoptosis only at high concentrations.
      CONCLUSION: Several of the traditional Chinese herbs, especially Venenum Bufonis
      and oxgall powder, may inhibit the growth of U(2)OS cell line, and the results of
      this study pave the way for further identification of the effective components in
      the herbs that inhibit osteosarcoma growth both in vivo and in vitro.

PMID- 16982439
TI  - [Contribution of endothelin and its receptors to ouabain-induced hypertension in
      rats].
AB  - OBJECTIVE: To investigate the effect of endothelin and its receptors on ouabain
      induced hypertension in rats. METHODS: Male Sprague-Dawley (SD) rats were treated
      with ouabain or saline for 6 weeks and their systolic blood pressure (SBP) were
      recorded weekly. At the end of 2, 4 and 6 weeks, respectively, the plasma and
      left ventricle endothelin contents were measured by radio-immunoassay, and real
      time quantitative RT-PCR was employed to determine the mRNA level of endothelin
      type A receptor (ETAR) and type B receptor (ETBR) in the left ventricle, and the
      protein expressions of ETAR and ETBR were examined by immuno-histochemistry.
      RESULTS: After 4 weeks of intraperitoneal ouabain injection, the mean SBP in
      ouabain group increased till reaching a level significantly higher than that in
      the control group after 6 weeks (P<0.001). The plasma and left ventricle
      endothelin contents were significantly increased after 2 weeks of ouabain
      injection (P<0.01), and similarly, increased ETAR mRNA was observed. After 4
      weeks of treatment, ETAR mRNA was increased continuously and the protein
      expression of ETAR upregulated in ouabain group as compared with the control
      group. The transcription and protein expression of ETBR were not altered by
      ouabain treatment. CONCLUSION: Before detectable blood pressure elevation occurs,
      endothelin concentration and ETAR can be already upregulated in ouabain-induced
      hypertensive rats, suggesting that endothelin might be involved in the
      cardiovascular effects of ouabain via an action on ETAR.

PMID- 16982440
TI  - [Molecular scanning of MODY1 gene mutations in pedigrees of early onset type 2
      diabetes in Beijing].
AB  - OBJECTIVE: To explore MDOY1 gene mutations in pedigrees of early-onset familial
      type 2 diabetes. METHODS: We collected 100 early-onset type 2 diabetes pedigrees
      in Beijing, in which the probands were diagnosed with type 2 diabetes before the
      age of 40 years with at least one first-degree relative having such a diagnosis
      before the age of 45 years. PCR was employed to amplify all the exons and
      exon/intron splice sites of MDOY1 gene and the PCR products were sequenced to
      identify the DNA variants. RESULTS: Two DNA variants in the noncoding region
      including IVS1C +44A>T and IVS2 -5C>T were identified, and 3 mutations in the
      coding region we identified M49V, T130I, and S462S were found in these pedigrees.
      CONCLUSION: Currently no sufficient evidence has been obtained to identify the
      variation in or near MDOY1 genes as the major cause of early-onset type 2
      diabetic in Chinese population.

PMID- 16982441
TI  - [Preliminary research of hepatocarcinoma stem cell markers].
AB  - OBJECTIVE: To study human hepatocarcinoma stem cell markers. METHODS: Tumor
      tissue samples were obtained from 8 patients with hepatic cellular cancer
      undergoing surgical tumor resection and the tumor cells were cultured with
      primary tissue culture in vitro. The cell subpopulations with each marker were
      isolated from the tumor cells by immunopanning using oval cell markers (CD34, c
      kit, Thy-1, CK7, CK19, CK14). The cells of each phenotype were injected into nude
      mice to measure their ability of tumor formation and the tumor mass was weighed
      one month after implantation. The tumorigenic subpopulations of the cells were
      injected into the nude mice again in 1/4 or 1/10 of their original densities to
      further analyze their ability of tumor formation. RESULTS: Among all the cell
      subpopulations, those positive for CD34, c-kit and CK7, respectively, showed
      marked difference from the negative cells in their ability of proliferation and
      tumor formation. The CD34(-), c-kit(+) and CK7(+) subpopulations of the cells
      exhibited strong capacity of tumor formation even in only 1/4 or 1/10 of their
      original density. CONCLUSIONS: There are heterogeneous subpopulations within
      human hepatocarcinoma with observable difference in tumor formation ability. The
      strong tumor formation ability of CD34(-), c-kit(+) and CK7(+) subpopulation of
      the cells suggests that CD34(-), c-kit(+) and CK7(+) represent part of the
      surface markers of hepatocarcinoma stem cells.

PMID- 16982442
TI  - [Expressions of vascular endothelial growth factor C and matrix
      metalloproteinases-2 and prognosis of non-small cell lung carcinoma].
AB  - OBJECTIVE: To investigate the expressions of vascular endothelial growth factor-C
      (VEGF-C) and matrix metalloproteinases-2 (MMP-2) proteins and its relationship
      with the biological behaviors of non-small cell lung carcinoma (NSCLC). METHODS:
      Immunohistochemical staining was used to detect the expressions of VEGF-C and MMP
      2 proteins in 42 cases of NSCLC tissues. The relationship of VEGF-C and MMP-2
      expressions was analyzed with the tumor size, lymphatic vessel density (LVD),
      histological type, differentiation, clinical recurrence, lymph node metastasis
      and patients' survival time. RESULTS: Out of the 42 cases of NSCLC, 23 and 26
      cases showed positive expressions of VEGF-C and MMP-2 proteins, respectively,
      with the expression rates of VEGF-C and MMP-2 protein of 54.8% and 61.9%,
      respectively. VEGF-C expression was positively associated with LVD and lymph node
      metastasis (P<0.05), and inversely with the differentiation of NSCLC and the
      patients' survival time (P<0.05). MMP-2 expression was positively associated with
      lymph node metastasis (P<0.05) and inversely with the patients' survival
      (P<0.05). VEGF-C and MMP-2 expressions was positively associated (r=0.469,
      P<0.05). CONCLUSION: The expressions of VEGF-C and MMP-2 proteins are closely
      associated with the biological behaviors of NSCLC, and their high expression
      suggests probable lymph node metastasis and poor prognosis.

PMID- 16982443
TI  - [Determination of arsenic content in Changtong oral liquid by inductively coupled
      plasma- mass spectrometry].
AB  - OBJECTIVE: To determine arsenic content in Changtong oral liquid, inductively
      coupled plasma-mass spectrometry (ICP-MS) was employed, which generated linear
      calibration curves in the range of 5-25 ng/ml for As (r=0.9998). The average
      recovery of As was 98.94% (n=5, RSD=2.58%).

PMID- 16982444
TI  - [Construction and identification of tetracycline-inducible rat Smad7 eukaryotic
      expression vector].
AB  - OBJECTIVE: To construct a tetracycline-inducible eukaryotic expression vector of
      rat Smad7. METHODS: The total RNA was extracted from normal rat kidney with
      Trizol agent. Rat Smad7 cDNA fragment was cloned by RT-PCR, and was inserted into
      the restriction site between Nhe I and Hind III of the inducible eukaryotic
      expression vector pBI-L by tetracycline. pBI-L-Smad7 was constructed by digestion
      and ligation, and detected by restriction endonuclease digestion and sequencing.
      RESULTS: The recombinant eukaryotic expression vector pBI-L-Smad7 was constructed
      correctly as confirmed by restriction endonuclease digestion and sequencing. The
      fragment of pBI-L-Smad7 digested with restriction endonucleases and the sequence
      of inserted Smad7 cDNA were consistent with the results of theoretical analysis.
      CONCLUSION: The tetracycline- inducible eukaryotic expression vector of rat
      Smad7, pBI-L-Smad7, is constructed successfully, which may facilitate further
      clinical study of Smad7 gene therapy for tissue and organ fibrosis.

PMID- 16982445
TI  - [Relationship between programmed cell death 5 protein expression and prognosis of
      renal clear cell carcinoma].
AB  - OBJECTIVE: To study the role of programmed cell death 5 (PDCD5) protein in the
      oncogenesis and development of renal clear cell carcinoma and its association
      with the prognosis of the malignancy. METHODS: PDCD5 expression was assayed
      immunohistochemically in 46 cases of human renal clear cell carcinoma, and the
      patients' survival was followed up. RESULTS: PDCD5 staining in the adjacent
      normal tissue of the tumor was significantly stronger than that in the tumor
      tissue, and PDCD5 expression was significantly correlated with the tumor grade,
      stage and prognosis. The tumors of high grade with strong invasive ability had
      much less PDCD5 expression and lighter staining. The three- or five-year survival
      rates of patients positive for PDCD5 expression was much higher than that of
      patients negative for PDCD5 expression. CONCLUSION: PDCD5 is a potent inhibitor
      of malignant transformation of renal clear cell carcinoma and may serve as a
      major predictor for evaluating the malignant potential and prognosis of the
      tumor.

PMID- 16982446
TI  - [Construction of prokaryotic expression plasmid pET15b-PEP-1-CAT and expression
      and purification of PEP-1-CAT fusion protein].
AB  - OBJECTIVE: To construct the prokaryotic expression plasmid pET15b-PEP-1-CAT to
      obtain purified fusion protein of PEP-1-CAT. METHODS: Using pfu DNA polymerase,
      the full-length human catalase cDNA was amplified by PCR from pZeoSV2(+)-CAT
      plasmid, and the PCR product was added with "A" using Taq DNA polymerase. The
      purified product of CAT cDNA with the base A at its 3' end was ligated with pGEM
      T Easy vector and transformed into DH5alpha. The correct recombinant was
      identified by PCR and Sal I/Bgl II digestion and named as pGEM-T-CAT. Two
      oligonucleotides were synthesized and annealed to generate a double-stranded
      oligonucleotide encoding the PEP-1 peptide, which was directly ligated into Nde
      I/Xho I-digested pET15b. The recombinant plasmid was identified by double-enzyme
      digestion and named as pET15b-PEP-1. pET15b-PEP-1 and pGEM-T-CAT were further
      digested by Xho I/BamH I and Sal I/Bgl II, respectively. The purified linear
      fragment of pET15b-PEP-1 and CAT cDNA fragment were ligated using two pairs of
      isocaudarners possessing different recognition sequences but producing compatible
      cohesive ends. The clone with the expected insert was selected using Xho I
      restriction analysis followed by sequence analysis. The recombinant plasmid was
      transformed into E. coli BL21(DE3) which was induced by IPTG. The recombinant
      protein possessed an N-terminal His-tag sequence which could be used to purify
      the target protein by affinity chromatography on a Ni(2+)-NTA-resin column. The
      fusion protein PEP-1-CAT was produced and confirmed by specific enzyme activity
      in vitro. RESULTS: Sequence analysis showed that the PEP-1 and the human CAT cDNA
      sequence of pET15b- PEP-1-CAT had identical sequence with designed PEP-1 peptide
      and human catalase cDNA sequence in GenBank (accession No. AY028632),
      respectively. SDS-PAGE and Western blotting confirmed successful expression and
      purification of PEP-1-CAT fusion protein with specific activity of 77.15 U/g.
      CONCLUSION: The prokaryotic expression plasmid pET15b-PEP-1-CAT has been
      constructed successfully, and the successful expression and purification of PEP-1
      CAT provides a basis for prevention and therapy of various disorders related to
      oxidative stress.

PMID- 16982447
TI  - [Reversed phase high-performance liquid chromatography for determination of
      plasma olanzapine and pharmacokinetics of olanzapine in healthy Chinese
      volunteers].
AB  - OBJECTIVE: To establish a reversed phase high-performance liquid chromatography
      (HPLC) system for determining plasma concentration of olanzapine and analyze the
      pharmacokinetics of olanzapine in healthy Chinese volunteers. METHODS: Ten
      healthy male subjects received a single oral dose of 20 mg olanzapine tablets.
      The plasma concentrations of olanzapine were determined by HPLC, and the data
      were analyzed using 3P97 program. RESULTS: The plasma concentration curve of
      olanzapine following a single oral dose conformed to the two compartment open
      model. The main pharmacokinetics parameters of olanzapine were as follow: C(max)
      was 113.7-/+33.1 microg/L, T(max) 5.07-/+0.65 h, t(1/2) 35.44-/+4.21 h, AUC(0
      144) 2,235-/+257 microg.h.L(-1), and AUC(0-inf) 2,516-/+301 microg.h.L(-1).
      CONCLUSION: The system established in this study allows for highly sensitive,
      selective and accurate determination of plasma concentration of olanzapine, and
      provides valuable information for clinical trials.

PMID- 16982448
TI  - [Expression of eosinophil major basic protein mRNA in bronchial asthma].
AB  - OBJECTIVE: To investigate the expression of eosinophil major basic protein (MBP)
      mRNA in bronchial asthma and explore its significance. METHODS: Peripheral blood
      eosinophil MBP mRNA levels were measured in 40 patients with asthma and 20 normal
      controls by semi-quantitative RT-PCR. The association of MBP mRNA levels with
      eosinophil count and pulmonary function was also analyzed. RESULTS: Compared with
      the normal control group, MBP mRNA level were significantly increased in asthma
      patients (0.37-/+0.11 vs 0.17-/+0.04, P<0.001), so was the eosinophil count (0.86
      /+0.52 vs 0.21-/+0.10, P<0.001). MBP mRNA levels in patients with moderate
      persistent asthma (0.42-/+0.05) and those with severe persistent asthma (0.47
      /+0.05) were significantly higher than those in patients with mild persistent
      asthma (0.25-/+0.06, P<0.001), and the difference in MBP mRNA levels between
      moderate persistent asthma patients and severe ones was also significant
      (P<0.05). Among the asthma patients, MBP mRNA levels showed an inverse
      correlation with pulmonary function (r=-0.7490, P<0.001). CONCLUSION: Increased
      MBP mRNA expression level may correlate with the severity of asthma. MBP may play
      an important role in the development of asthma.

PMID- 16982449
TI  - [Ultrastructural changes of the extraintestinal organs of newborn mice with human
      rotavirus infection].
AB  - OBJECTIVE: To investigate the ultrastructural changes of the extraintestinal
      organs of newborn mice with human retrovirus (RV) infection to probe into the
      mechanism and clinical diagnose and therapy of extraintestinal RV infection.
      METHODS: Human RV was inoculated into the abdominal cavity of the newborn mice,
      and the ultrastructural changes of the heart, lung, livers, and kidneys of the
      infected and control mice were observed by transmission electron microscope.
      RESULTS: The mice with intraabdominal RV injection showed pathological changes of
      the cells in the small intestinal villus, liver, and kidneys. Shortened small
      intestinal villus, nuclear membrane disorganization, massive vacuolization,
      mitochondrial swelling and rough endoplasmic reticulum dilation were observed in
      the cells of the small intestinal. In the liver of the mice, marked mitochondrial
      swelling and agglutination, cell nucleus pyknosis or collapse, presence of
      numerous lipid droplets and vacuoles were seen in the liver cells, with
      lymphocyte and plasmacyte infiltration. Obvious dilatation and shedding of the
      microvillus were seen in cholangioles. The mitochondria of the proximal
      convoluted renal tubule showed mild swelling, but the cells in the heart and lung
      did not display obvious changes. CONCLUSION: The small intestinal villi were
      highly susceptible to RV infection, and systemic spread of human RV may cause
      damage of various extraintestinal organs especially the liver, which can also be
      susceptible to RV.

PMID- 16982450
TI  - [Evaluation of cyclodextrin inclusion of the volatile components in compound
      traditional Chinese medicine].
AB  - OBJECTIVE: To study the factors affecting cyclodextrin (CD) inclusion of the
      volatile components in compound traditional Chinese medicines and evaluate the
      stability of the inclusion compound. METHODS: This study took Gengnian compound
      as an example to examine the factors affecting the inclusion process according to
      the inclusion compound utilization ratio. Orthogonal design method was employed
      optimize the parameters in the inclusion process. The moisture absorption rate of
      the beta-CD inclusion compound was determined in different humidity and Q10 was
      used to predict its. RESULTS: The inclusion method, inclusion compound dosage,
      temperature, inclusion time, and the drying method could all obviously influence
      the inclusion process. The results of orthogonal design study showed that the
      optimal beta-CD inclusion of Gengnian compound volatile components could be
      achieved by adding 8-fold volume of beta-CD and stirring for 3 h at room
      temperature. Stability experiment showed that the humility did not significantly
      influence the inclusion compound, which can be stable for 1.26 years. CONCLUSION:
      This study comprehensively examines the factors affecting the inclusion process
      and the stability of the inclusion compound, and provides experimental basis for
      application and study of the inclusion technology.

PMID- 16982451
TI  - [Growth differentiation factor-9 gene expression in in vitro cultured oocytes in
      mice].
AB  - OBJECTIVE: To explore the relation between oocyte maturation and growth
      differentiation factor-9 (GDF-9) gene expression. METHODS: Ovariectomy was
      performed in 50 Kunming female mice of 10 days old, and the preantral follicles
      were isolated from the ovaries and cultured in medium drops for 12 days. Oocytes
      and somatic cells were mechanically isolated. The oocytes cultured in vitro for
      2, 4, 6, 8, 10, and 12 days constituted the in vitro cultured group and the
      oocytes obtained from female mice of 12, 14, 16, 18, 20, and 22 days old served
      as the in vivo group. Semi-quantitative RT-PCR and agar gel electrophoresis were
      performed to quantify GDF-9 gene expression in each oocyte. RESULTS: Follicle
      survival, antrum formation and maturation rate was 89.5%, 51.8% and 56.6% in the
      in vitro cultured follicles, respectively. GDF-9 gene expression on days 2, 4, 6,
      8, 10, and 12 in in vitro cultured oocytes was 0.83-/+0.08, 0.52-/+0.09, 0.45
      /+0.13, 0.49-/+0.09, 0.49-/+0.09, and 0.68-/+0.08, respectively; GDF-9 gene
      expression in in vivo grown oocytes of 12, 14, 16, 18, 20, and 22 days were 0.64
      /+0.35, 0.48-/+0.10, 0.52-/+0.10, 0.66-/+0.08, 0.72-/+0.09, and 0.91-/+0.11,
      respectively. Between days 8 and 12, GDF-9 gene expression in in vitro cultured
      oocyte was significantly lower than that in in vivo grown oocytes (P<0.05).
      CONCLUSION: MII oocytes can be obtained from in vitro culture of the preantral
      follicles. GDF-9 gene expression in the oocytes varies with their growth stages.
      Between days 8 and 12 of in vitro culture, GDF-9 gene expression in the cultured
      oocytes is different from that in in vivo grown oocytes.

PMID- 16982452
TI  - [Jingjielianqiao Decoction promotes leg ulcer healing in rabbits].
AB  - OBJECTIVE: To study the effect of Jingjielianqiao Decoction in promoting leg
      ulcer in rabbits. METHODS: Nine adult male New Zealand albino rabbits with
      chronic leg ulcers were randomized into 3 groups, namely group A treated with
      Jingjielianqiao Decoction, group B with Shengjiyuhong Decoction, and group C with
      normal saline. Gross observation of the wounds was carried out regularly for
      evaluating the changes in the ulcerous area, depth and wound surface excretion.
      After 3 weeks of treatment, the tissues on the edge of the ulcer were sampled and
      prepared for routine pathological examination, electron microscopy and
      immunohistochemistry for vascular endothelial growth factor (VEGF) and CD34. The
      number of blood vessels and their areas were also recorded. RESULTS: The wounds
      showed no significant differences between the 3 groups by gross observation
      during the treatment, but after completion of the 3-week treatment, routine
      pathological examination and electron microscopy revealed significant differences
      between the groups. Immunohistochemistry for VEGF and CD34 yielded comparable
      results between groups A and B (positive control), but showed significant
      differences between group C and the other two groups (P<0.01). CONCLUSION:
      Jingjielianqiao Decoction and Shengjiyuhong Decoction can obviously promote the
      healing of leg ulcer in rabbits.

PMID- 16982453
TI  - [Clinical study of early interventions for ABO hemolytic disease of the newborn].
AB  - OBJECTIVE: To investigate therapeutic effect of high-dose intravenous
      immunoglobulin (IVIG) for early management of ABO hemolytic disease of the
      newborn (ABO-HDN). METHODS: A total of 121 cases with ABO-HDN were randomly
      divided into treatment group (n=61) and control group (n=60). In addition to the
      routine treatment of the control group, IVIG were given at a daily dose of 400
      mg/kg to the cases in the treatment group for 2-3 times, and therapeutic effects
      were evaluated and compared between the two groups. RESULTS: The serum total
      billirubin concentration on the third day after treatment (153.42-/+45.21
      micromol/L) and mean daily serum total billirubin concentration reduction (56.49
      /+24.05 micromol/L) in treatment group were lower than those in the control group
      (P<0.01). The jaundice resolution time (23.51-/+11.19 h) and the phototherapy
      time (3.01-/+0.89 h) for billirubinemia treatment in treatment group were shorter
      than those in the control group (P<0.01). The patients in the the treatment group
      had higher hemoglobin level after treatment (15.59-/+2.01 g/L) than those of the
      control group (P<0.01). CONCLUSION: High-dose IVIG can effectively arrest the
      progression of hemolytic disease, quickly reduce serum total billirubin
      concentration and shorten phototherapy time for early treatment of ABO-HDN.

PMID- 16982454
TI  - [Influence of transforming growth factor beta1 on long-term renal allograft
      function].
AB  - OBJECTIVE: To determine the association between urine transforming growth factor
      beta(1) (TGF-beta(1)) concentration and long-term renal allograft function.
      METHODS: Patients undergoing kidney transplantation between August 1, 1999 and
      June 30, 2001 and survived for one year with normal renal functions were
      investigated. The blood and urine TGF-beta(1) concentrations were tested at an
      interval of at least 6 months. Totally 134 patients completed the 3-year follow
      up investigation. Correlation between their renal functions (creatinine clearance
      rates) and their urine relative TGF-beta(1) concentrations 1 year after renal
      transplantation were determined. Of the 134 renal recipients, 16 were diagnosed
      to have chronic allograft nephropathy (CAN), and their blood and urine TGF
      beta(1) concentrations 1 year after renal transplantation were compared with
      those of the recipients free of CAN. RESULTS: There was a positive correlation
      between long-term renal functions (loss of creatinine clearance rates) and in
      relative concentration of TGF-beta(1) urine 1 year after renal transplantation.
      The urine TGF-beta(1) concentrations of CAN and CAN-free recipients 1 year after
      transplantation were 182.7-/+40.2 and 398-/+33.5 pg/mg.Cr, respectively, showing
      significant differences. The blood TGF-beta(1) concentrations of CAN and CAN-free
      recipients were comparable (32.1-/+4.7 and 31.9-/+4.8 ng/ml, respectively).
      CONCLUSION: Urine TGF-beta(1) is significantly elevated even before the onset of
      renal dysfunction in patients with CAN, and urine TGF-beta(1) level in early
      stage after renal transplantation can help predict long-term renal function.

PMID- 16982455
TI  - [Detection and typing of dengue virus using polymerase chain reaction and
      microwell plate hybridization].
AB  - OBJECTIVE: To establish a specific, sensitive and practicable method for
      detection and typing of dengue virus. METHODS: Based on the genomic sequence
      analysis of dengue virus types 1-4, 4 pairs of primers were designed. The
      specific capture probes of dengue virus types 1-4 were amplified using RT-PCR,
      cloned and sequenced before using them for precoating the microwell plate. The
      samples were amplified using biotin-labeled forward primer and reverse primer,
      and microwell plate hybridization was carried out for detection and typing of
      dengue virus types 1-4. RESULTS: The absorbance of the positive samples were
      higher than 0.5, while the average absorbance of the negative samples was lower
      than 0.1, with the S/N higher than 10. CONCLUSION: The method of PCR-ELISA we
      established for early detection and typing of all 4 dengue viruses seretypes.

PMID- 16982456
TI  - [Effects of irbesartan on nitric oxide system in the heart of diabetic rats].
AB  - OBJECTIVE: To investigate the effects of irbesartan for heart protection and on
      heart nitric oxide (NO) system in diabetic rats. METHODS: Thirty adult male
      Wistar rats were randomly divided into three equal groups, namely control group,
      diabetes group and irbesartan group. Streptozotocin (STZ, 50 mg/kg) was injected
      to the abdomen to induce diabetes in the rats. After treatment for 12 weeks, the
      rats were sacrificed and the urine volume, body weight, ratio of heart to body
      weight, plasma glucose and glycosylated hemoglobin (HbA1c) were measured. NO
      levels in the serum and myocardium were determined. Inducible nitric oxide
      synthase (iNOS) expression was determined by immunohistochemistry, and iNOS mRNA
      detected by RT-PCR. RESULTS: Urine volume, ratio of heart to body weight, plasma
      glucose, HbA1C, NO levels in the urine, blood and myocardium in diabetic and
      irbesartan rats were significantly greater than those of normal controls
      (P<0.05). The ratio of heart to body weight and NO levels of urine, serum and
      heart tissue in rats of irbesartan group were significantly decreased as compared
      with those of diabetes rats (P<0.05). Myocardium iNOS mRNA and protein expression
      decreased significantly in irbesartan group, but not in diabetes group.
      CONCLUSIONS: The abnormality in NO and iNOS mRNA expression might be related to
      diabetic cardiomyopathy. Irbesartan can decrease iNOS mRNA and protein
      expressions and reduce NO levels in STZ-induced diabetic rats.

PMID- 16982457
TI  - [Effect of resveratrol on lipopolysaccharide-induced activation of rat peritoneal
      macrophages].
AB  - OBJECTIVE: To investigate nuclear factor kappa B (NF-kappaB) activation induced
      by lipopolysaccharide (LPS) in rat peritoneal macrophages (PMAs) and the
      inhibitory effect of resveratrol on NF-kappaB activation. METHODS: PMAS from
      normal SD rats were randomly divided into 7 groups, including a control group, a
      LPS group and 5 resveratrol groups (I-V). PMAs of the control group were
      incubated in DMEM, and those in LPS group in DMEM containing LPS (10 microg/ml).
      PMAS of resveratrol groups I-V were incubated in DMEM containing LPS (10
      microg/ml) and different concentrations of resveratrol. After 24 h of incubation,
      NF-kappaB activation in the PMAs was determined, and the expression levels of
      tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and nitric oxide
      (NO) in the culture medium were measured. RESULTS: Exposure to LPS resulted in an
      excessive enhancement of cytokine and NO expressions in the PMAs. Resveratrol at
      1.25-10 microg/ml produced a dose- dependent inhibition of cytokine and NO
      expressions and on NF-kappaB activation in LPS-stimulated PMAs. CONCLUSION:
      Resveratrol can inhibit LPS-induced NF-kappaB activation in rat PMAs and
      subsequently suppress the expressions of TNF-alpha, IL-1 and NO.

PMID- 16982458
TI  - Phase I trial of PT-100 (PT-100), a cytokine-inducing small molecule, following
      chemotherapy for solid tumor malignancy.
AB  - PT-100 upregulates cytokine expression competitively inhibiting the dipeptidyl
      peptidase activity of fibroblast activation protein (FAP) and dipeptidyl
      peptidase IV (DPP-IV). This dose-escalation study was conducted to evaluate the
      safety of PT-100 in patients receiving myelosuppressive chemotherapy and to
      assess its effects on neutrophil recovery.PT-100 was administered orally for 7
      days as a 200 microg, 400 microg, 800 microg, or 1,200 microg total daily dose
      (divided twice daily) to 6, 6, 17, and 5 patients, respectively. Patients
      received 2 cycles of chemotherapy: The first cycle served as each individual
      patient's control. Patients had to develop Grade 3+ neutropenia in Cycle 1 in
      order to receive PT-100 in Cycle 2. Most patients received PT-100 on Days 2-8 of
      chemotherapy in Cycle 2, except at 800 microg where an additional cohort (n = 8)
      was treated on a Days 5-11 schedule. Five of 7 patients receiving 800 microg on
      Days 2-8 experienced a >/=1-day improvement in Grade 3+ neutropenia in Cycle 2
      versus Cycle 1. Overall, PT-100 was well tolerated. A reduction in chemotherapy
      related nausea, vomiting, fatigue, alopecia, and diarrhea was noted in patients
      receiving PT-100. Edema/peripheral swelling, hypotension, hypovolemia, and
      dizziness were the most common nonhematologic adverse events considered related
      to PT-100. Two Grade 3 adverse events were considered related to PT-100: syncope
      (1,200 microg) and orthostatic hypotension (800 microg). A maximum tolerated dose
      was not reached. Given the accelerated neutrophil recovery, preclinical evidence
      of antitumor activity, and tolerable toxicities of PT-100, additional studies to
      optimize the PT-100 dosing schedule in patients receiving myelosuppressive
      chemotherapy are needed.

PMID- 16982459
TI  - Iron absorption during epoetin alfa therapy for chemotherapy-associated anaemia.
AB  - Absorption of a physiological dose of ferrous iron was studied in 18 patients
      with solid malignancy receiving epoetin therapy for mild chemotherapy-associated
      anemia. The historical control group consisted of 25 iron replete volunteers
      (iron absorption 20 +/- 11% in males and 26 +/- 13% in females) and 21 patients
      with uncomplicated iron deficiency (iron absorption 71 +/- 19%). Iron absorption
      was increased in the majority of the cancer patients (iron absorption 59 +/-
      35%). There were no significant differences in iron absorption between cancer
      patients who were iron replete or iron deficient according to current clinical
      practice guidelines (iron deficiency: transferrin saturation < 20% and/or serum
      ferritin < 100 ng/mL). Red cell iron incorporation was not disturbed in the
      majority (89%) of patients.

PMID- 16982460
TI  - A novel 3-d model of chick chorioallantoic membrane for ameliorated studies in
      angiogenesis.
AB  - Decisive indulgence of angiogenesis requires a more holistic assessment and
      several in vivo assays have been developed that permit a more realistic appraisal
      of the angiogenic response. One of the most popular assays to study angiogenic
      activity is the chick chorioallantoic membrane (CAM). Although CAM assay is a
      vital technique used to study normal and putative angiogenesis, a serious
      drawback in its utilization is the lack of quantitative assessment of
      vascularization. In this study, we proposed a new 3-D model of the developing CAM
      for precise quantification of normal vasculature of CAM from Day 4 to Day 13 of
      incubation. Image probing technique was used to quantify different 3-D parameters
      of vascular microarchitecture. A significant increase (P < 0.05) in surface
      roughness (Sa) was observed at Day 5 of incubation, while highly significant
      increase (P < 0.01) in Sa values was observed at Day 6 of incubation. Maximum
      increase (P < 0.001) in Sa values was observed from Day 7 to Day 9 of incubation
      and slight decrease in Sa values was observed in successive days. Similar results
      were observed for root mean square values (Sq), absolute heights of the surface
      (Sz), and amount of lowest valleys (Sy) on CAM. A significant increase (P < 0.05)
      in developed surface area (Sdr) from Day 5 of incubation, reaching to its maximum
      (P < 0.01) at Day 9 also was noted. Similarly, significant increase (P < 0.05) in
      fluid core retention (Sci) illustrates presence of copious fluid in blood
      vessels. Image probing technique offers a useful modality for visualizing 3-D
      microvascular architecture of CAM to exaggerate the fine details and reveal the
      hidden information that can be helpful for precise quantification of
      angiogenesis. This approach can be used to evaluate the angiogenic and
      antiangiogenic potential of different biological substances and also can be a
      valuable independent prognostic indicator in a wide variety of human cancers.

PMID- 16982461
TI  - Serum vascular endothelial growth factor (VEGF) and bcl-2 levels in advanced
      stage non-small cell lung cancer.
AB  - The characteristic changes in cancer process are assumed to be genetic
      alterations about the imbalance of cell proliferation and apoptotic cell death.
      This study was conducted to determine the value of the circulating vascular
      endothelial growth factor (VEGF) and Bcl-2 in patients with advanced stage non
      small cell lung cancer (NSCLC). These serum factors were measured of 52 NSCLC
      patients pathologically verified on before and after chemotherapy in comparison
      with 16 healthy controls by using ELISA method. Both of the serum levels of VEGF
      (p = 0.015) and Bcl-2 (p < 0.001) were increased significantly in NSCLC patients
      compared with the healthy controls. No statistically significant relationships
      between investigated elevated serum parameters and various characteristics of
      patients and disease such as stage and tumor burden were determined. Likewise, we
      also found no correlation between serum VEGF and Bcl-2. Cytotoxic therapy of
      patients was accompanied by unchanged serum levels of serum factors. The median
      survival of all patients was 27 weeks and one-year survival rate was 22.4
      percent. With the median serum levels as the cut-off value, patients were divided
      into high- and low-serum parameter groups. While we found that patients'
      performance status (p < 0.0001), serum LDH level (p = 0.0002), response to
      chemotherapy (p = 0.0023), and stage of the disease (p = 0.0085) were prognostic
      factors for survival, serum VEGF (p = 0.48) and Bcl-2 (p = 0.91) levels were
      determined as ineffective on survival in patients with advanced NSCLC. In
      conclusion, our data suggest that these serum factors, VEGF and Bcl-2, are useful
      diagnostic factors, not predictive and prognostic markers for overall survival in
      advanced NSCLC patients.

PMID- 16982462
TI  - Cyclin e expression and prognosis in breast cancer patients: a meta-analysis of
      published studies.
AB  - In vitro studies showed that cyclin E can accelerate the cell cycle by shorten
      the G1/S phase transition. Therefore, varieties of studies have investigated the
      relationship between cyclin E and survival in breast cancer patients. However,
      the results differed widely between studies. We reviewed the published studies
      and performed a meta-analysis, which including 12 independent studies and 2,534
      patients. The combined HR estimate for relapse-free survival (RFS) was 2.32 (95%
      CI, 1.25-4.30) and 1.72 (95% CI, 0.95-3.10) in univariate and multivariate
      analysis, respectively. In addition, the combined HR estimate for overall
      survival (OS) and breast cancer specific survival (BCSS) was 2.98 (95% CI, 1.85
      4.78) and 2.86 (95% CI, 1.85-4.41) in univariate and multivariate analysis,
      respectively. In conclusion, the high level of cyclin E appears to be an
      independent prognostic factor to OS/BCSS of breast cancer patients but not to
      RFS.

PMID- 16982463
TI  - Tocopherols and saponins derived from Argania spinosa exert, an antiproliferative
      effect on human prostate cancer.
AB  - The aim of our study is to evaluate the antiproliferative effect of tocopherols
      obtained from alimentary virgin argan oil extracted from the endemic argan tree
      of Morocco and of saponins extracted from argan press cake on three human
      prostatic cell lines (DU145, LNCaP, and PC3). The results were compared to 2
      methoxyestradiol as antiproliferative drug candidates. Cytotoxicity and
      antiproliferative effects were investigated after cells' treatment with
      tocopherols and saponins compared to 2-Methoxyoestradiol as the positive control.
      Tocopherols and saponins extracted from argan tree and 2-methoxyestradiol exhibit
      a dose-response cytotoxic effect and an antiproliferative action on the tested
      cell lines. The best antiproliferative effect of tocopherols is obtained with
      DU145 and LNCaP cell lines (28 microg/ml and 32 microg/ml, respectively, as
      GI50). The saponins fraction displayed the best antiproliferative effect on the
      PC3 cell line with 18 microg/ml as GI50. Our results confirm the
      antiproliferative effect of 2-methoxyestradiol and show for the first time the
      antiproliferative effect of tocopherols and saponins extracted from the argan
      tree on hormone-dependent and hormone-independent prostate cancer cell lines.
      These data suggest that argan oil is of potential interest in developing new
      strategies for prostate cancer prevention.

PMID- 16982464
TI  - Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab
      as salvage treatment for patients with relapsed or refractory aggressive non
      Hodgkin's lymphoma.
AB  - We designed a multicenter Phase II trial to prospectively evaluate the efficacy
      and safety of the combination of rituximab with the DHAP regimen (dexamethasone,
      high-dose cytarabine, cisplatin) in patients who relapsed after or were resistant
      to a CHOP-like regimen. A total of 53 patients with relapsed or resistant
      aggressive B-cell NHL were analyzed. The overall response rate was 62.3 percent.
      With a median follow-up of 24.9 months, median overall and progression-free
      survivals were 8.5 and 6.7 months, respectively. Immunochemotherapy with
      rituximab and DHAP proved to be feasible and effective in this patient
      population.

PMID- 16982465
TI  - Prolactin promotes growth of a spontaneous T cell lymphoma: role of tumor and
      host derived cytokines.
AB  - The present study was conducted to investigate the effect of prolactin (PRL) on
      the progressive growth of a T cell lymphoma. Using a murine model of a
      transplantable T cell lymphoma, designated as the Dalton's lymphoma (DL) it is
      shown that in vivo administration of PRL to tumor bearing mice reduces the
      survival duration of tumor-bearing host due to an augmentation of tumor growth.
      In vitro studies demonstrated that PRL directly stimulates the proliferation of
      DL cells in a dose and time dependent manner. PRL-treated DL cells showed an
      increase in cell size along with a decrease in cells with apoptotic morphology.
      Evidence also is presented to show the involvement of tumor and macrophage
      derived cytokines: IL-1, IL-2, TGF-beta, and M-CSF in PRL-dependent augmentation
      of tumor growth. Moreover, PRL treatment was found to inhibit Caspase-activated
      DNase (CAD) expression in DL cells indicating that PRL acts through modulation of
      caspase dependent pathway of apoptosis. The study is of novel significance as it
      demonstrates for the first time that PRL can promote growth of a T cell lymphoma
      involving host and tumor-derived tumor growth promoting cytokines.

PMID- 16982466
TI  - Four primary malignancies successively occurred in a BRCA2 mutation carrier: a
      case report.
AB  - Carriers of BRCA2 germline mutation have a significantly increased lifetime risk
      of breast and ovarian cancer compared to non carriers. Several other carcinomas
      seem to be associated with BRCA2 mutations: pancreas, prostate, larynx,
      gallbladder, bile duct cancer, and malignant melanoma. We described a case of a
      67-year-old BRCA2 mutation carrier of Caucasian, non-Jewish, ethnic origin who
      successively developed 4 primary malignancies in 30 months: breast ductal
      carcinoma, chronic lymphatic leukemia, ovarian serous papillary carcinoma, and
      endocervical adenocarcinoma. This is the first case of 4 primary malignancies in
      a BRCA mutation carrier, also occurred in such a short observation period.
      Chronic lymphatic leukemia and endocervical adenocarcinoma have not been yet
      associated to BRCA2 germline mutation.

PMID- 16982467
TI  - An atypical presentation of thymoma with diffuse pleural dissemination mimicking
      mesothelioma.
AB  - Although rare, thymoma is the most frequent type of malignancy in the anterior
      mediastinum. On most occasions, radiological diagnosis is easy, owing to current
      imaging studies like computerized tomography. Additionally, the radiological
      diagnosis of thymoma can be differentiated easily from malignant pleural
      mesothelioma in most cases. However, thymoma's differentiation from lymphoma,
      thymic hyperplasia, or thymic remnants sometimes may pose diagnostic challenges.
      Here, we report a case of advanced thymoma mimicking malignant pleural
      mesothelioma, with circumferential encasement of the lung. A brief review of the
      literature with special reference to radiological imaging on thymoma also is
      presented.

PMID- 16982468
TI  - Euthanasia: an overview and the jewish perspective.
AB  - BACKGROUND: End-of-life care poses fundamental ethical problems to clinicians.
      Defining euthanasia is a difficult and complex task, which causes confusion in
      its practical clinical application. Over the course of history, abuse of the term
      has led to medical atrocities. Familiarity with the relevant bioethical issues
      and the development of practical guidelines might improve clinical performance.
      OBJECTIVE: To define philosophical concepts, to present historical events, to
      discuss the relevant attitudes in modern bioethics and law that may be helpful in
      elaborating practical guidelines for clinicians regarding euthanasia and end-of
      life care. Concepts found in the classic sources of Jewish tradition might shed
      additional light on the issue and help clinicians in their decision-making
      process. METHODS: An historical overview defines the concepts of active versus
      passive euthanasia, physician-assisted suicide and related terms. Positions found
      in classical Jewish literature are presented and analyzed with their later
      interpretations. The relevance and application in modern clinical medicine of
      both the general and Jewish approaches are discussed. RESULTS: The overview of
      current bioethical concepts demonstrates the variety of approaches in western
      culture and legal systems. Philosophically and conceptually, there is a crucial
      distinction between active and passive euthanasia. The legitimacy of active
      euthanasia has been the subject of major controversy in recent times in various
      countries and religious traditions. CONCLUSION: The historical overview and the
      literature review demonstrate the need to provide clearer definitions of the
      concepts relating to euthanasia, for in the past the term has led to major
      confusion and uncontrolled abuse. Bioethical topics should, therefore, be
      included in medical training and continuing education. There are major debates
      and controversies regarding the current clinical and legal approaches. We trust
      that classical Jewish sources might contribute to the establishment of clinical
      definitions, meaningful approaches and practical guidelines for clinicians.

PMID- 16982469
TI  - Pharmacogenomics of colorectal cancer prevention and treatment.
AB  - Pharmacogenomic tools are beginning to emerge that will provide guidance in the
      treatment and prevention of colorectal cancer. Significant individual genetic
      variation exists in drug metabolism of 5FU, capecitabine, irinotecan, and
      oxaliplatin that influences both the toxicity and efficacy of these agents.
      Recent FDA approval of genetic testing for mutations in the UGT1A1 gene that
      predict adverse reactions to irinotecan is ushering in a new era that will
      increasingly rely on genotyping to individualize treatment decisions for patients
      with cancer as well as for patients at high risk who may be candidates for
      chemoprevention agents. This review focuses on current knowledge regarding key
      mutations and polymorphisms which affect outcomes for colorectal cancer patients,
      as well as the pharmacogenetics of chemoprevention trials.

PMID- 16982470
TI  - Targeted therapy for renal cell carcinoma: a new therapeutic paradigm.
AB  - Renal cell carcinoma is the most common tumor of the kidney. It has an
      unpredictable behavior and poor response to systemic therapy. Developing newer
      therapy for this disease is a priority considering the high recurrence rate and
      the small subset of patients who benefit from the use of cytokines such as
      interferon-alpha or interleukin-2. Identifying molecular targets and targeting
      various biomarkers has revolutionized the therapeutic approach to advanced and
      metastatic renal cell carcinoma. Although some of the antiangiogenic agents and
      receptor tyrosine kinase inhibitors appear promising, further understanding of
      their mechanism of action and the patient population who would benefit most from
      such agents is still being explored. As numerous targeted agents are entering the
      clinical investigation arena in a relatively short period of time, newer
      challenges in renal cell carcinoma therapeutics are emerging. Some of the future
      challenges in using targeted antineoplastic agents in renal cell carcinoma will
      include evaluating their long-term safety and benefit, using the particular drug
      in the appropriate patient population after appropriate stratification and
      studying the combination of some of these drugs for synergy or additive effects.

PMID- 16982472
TI  - Skull and mandible formation in the cuckoo (Aves, Cuculidae): contributions to
      the nomenclature in avian osteology and systematics.
AB  - The study of the contributions of different bones to the formation of the
      skeleton in birds is necessary: (1) to establish homologies in comparative
      anatomy; (2) to delimit each bone structure correctly, mainly in relation to the
      skull and mandible where the bones are fused to each other in adults; and (3) to
      standardize nomenclature in avian osteology. In this paper at least one young
      specimen belonging to each sub-family of Cuculidae was examined in order to
      identify each bone in terms of boundaries and contributions to skull and mandible
      formation. These cuckoos specimens were also compared with adults and young of
      turacos and hoatzin. The results show little variation of skull and jaw among the
      young cuckoos studied compared with the variations among adult specimens.
      However, it provides new suggestions for the boundaries and nomenclature of
      certain osseous structures in the skull and mandible of birds, specifically
      fissura zona flexoria craniofacialis, prominetia frontoparietalis, crista
      temporalis transversa, processus squamosalis, fossa laterosphenoidalis,
      tuberculum laterosphenoidale and processus retroangularis. This study also
      provides more reliable homologies for use in cladistic analysis and above all it
      contributes to the phylogenetic position of Cuculidae within Neognathae,
      specifically the skull formation suggest that turacos and hoatzin are more
      similar to each other than either is to the cuckoos.

PMID- 16982473
TI  - Plexiform vascular structures in the human digital dermal layer: a SEM--corrosion
      casting morphological study.
AB  - This study aimed to describe the impressive diversity of vascular plexiform
      structures of the hypodermal layer of human skin. We chose the human body site
      with the highest concentration of dermal corpuscles, the human digit, and
      processed it with the corrosion casting technique and scanning electron
      microscopy analysis (SEM). This approach proved to be the best tool to study
      these microvascular architectures, free from any interference by surrounding
      tissues. We took high-definition pictures of the vascular network of sweat
      glands, thermoreceptorial and tactile corpuscles, the vessels constituting the
      glomic bodies and those feeding the hair follicles. We observed that the three
      dimensional disposition of these vessels strictly depends on the shape of the
      corpuscles supplied. We could see the tubular vascularization of the excretory
      duct of sweat glands and the ovoid one feeding their bodies, sometimes made up of
      two lobes. In some cases, knowledge of these morphological data regarding the
      normal disposition in space and intrinsic vascularization structure of the dermal
      corpuscles can help to explain many of the physiopathological changes occurring
      during chronic microangiopathic diseases.

PMID- 16982474
TI  - A comparison of different embalming fluids on the quality of histological
      preservation in human cadavers.
AB  - There are significant problems in obtaining normal human material for histology
      for teaching or research purposes. This study shows that tissue from cadavers
      embalmed for teaching can be used for routine histology. Twelve cadavers embalmed
      with four different formalin-containing embalming fluids were used (n = 3 per
      fluid): (1) formalin mix (10% formalin); (2) Dunedin mix (an alcohol-based fluid
      containing phenol); (3) Michigan mix (a water-based fluid); and (4)
      phenoxyethanol mix (an alcohol-based fluid containing phenoxyethanol). Tissue
      blocks of liver, heart, kidney, skin and skeletal muscle were taken from each
      cadaver, paraffin embedded, sectioned and stained with haematoxylin and eosin (H
      & E), Periodic Acid Schiff (PAS), or Mallory trichrome (Malt). Each section was
      assigned an overall score based on the histological quality of the cellular
      components of the tissue. Sections were scored from 1 to 3 (1 = poor, 2 =
      satisfactory, 3 = good). Satisfactory sections were obtained from all cadavers
      except those embalmed with the Dunedin mix. The Michigan and phenoxyethanol
      fluids resulted in consistently good quality sections. No significant differences
      in tissue morphology were observed between the different stains. The clearest
      morphology was observed in the skin and skeletal muscle sections, and in tissues
      embalmed with fluids which do not contain phenol.

PMID- 16982475
TI  - Lumbar ontogenetic allometry and dimorphism in humans. A case for comparison
      between interspecific and intraspecific scaling.
AB  - The ontogenetic allometry of the lumbar region of 1913 humans (1228 females and
      685 males), ranging from newborn to 21-year-old individuals, was studied by means
      of length, width, projected surface area and bone mineral density of the segment
      L2 - L4, obtained by dual X-ray absorptiometry (DXA). All these parameters were
      regressed to body mass and height of the individuals, considered alternatively as
      the independent variable. Firstly, we addressed the comparison between the
      results obtained on both sexes in order to elucidate whether ontogenetic
      differences existed. Length of the segments increased significantly faster in
      females than in males, independently whether the regression was made against body
      mass or height, while in both types of regression width scaled in males faster
      than in females. Regarding bone mineral density, although males increased bone
      mineral density faster than females, slope differences were not significant.
      However, y-interception was significantly higher in females than in males when
      bone mineral density was regressed to body mass. Results on length and width are
      compared with others from previous research on allometry. Finally, global results
      are discussed as regards the slope predictions for interspecific scaling.

PMID- 16982476
TI  - Mechanical anisotropy in cobra skin is related to body movement.
AB  - The mechanical breaking stress and strain of cobra leather, along with their
      mechanical anisotropies, were studied in relation to body movement. The
      mechanical breaking strain in the transverse direction (TD), which was
      perpendicular to the direction (CCD) from the caudal to the cranial end, was much
      larger around the dorsum, and slightly larger around the abdomen, than that in
      the CCD. The mechanical strain is closely related to the expansion of skin. The
      mechanical anisotropy of cobra leather was relatively large in the dorsum, but
      smaller in the abdomen. These findings indicate that it was comparatively easy
      for the cobra body to expand preferentially in the TD around the dorsum and also
      to expand roughly equally in all directions around the abdomen, whereas expansion
      of the dorsum in the CCD was restricted by the spinal column. These findings also
      suggest that the strong mechanical anisotropy in cobra leather is closely related
      to the motion of the skin around the waist, which accompanies movement of the
      body.

PMID- 16982477
TI  - Influence of high-calorie (cafeteria) diets on the population of Paneth cells in
      the small intestine of the rat.
AB  - A high-calorie (cafeteria) diet is known to cause changes in the intestinal
      morphology and functioning that seem to be related to calorie overfeeding. Among
      the cell lineages found in the small intestine epithelium, the Paneth cell (PC)
      population is known to be influenced by factors related mainly to the intestinal
      microbiota. The role of PCs in the intestinal cell concert remains unclear,
      because experimental evidence suggests PC involvement in local processes other
      than protection against pathogens. Participation of PC in digestive mechanisms
      has been proposed on this basis. We have analyzed the effect of high-carbohydrate
      (HC) and high-fat (HF) cafeteria diets on the PC population in the small
      intestine of the adult rat. For 8 weeks, both HC and HF diets caused a gain in
      body weight, but whereas the HC-fed rats showed reduced counts of intestinal
      crypts per 5-mum section, the HF-fed group showed the opposite. In control rats,
      the number of crypts per section showed a slight tendency to decrease along the
      duodenum - ileum axis, whereas the number of PCs per crypt was increased towards
      the ileum. As a result, the number of PCs per section (calculated from these
      data) remained constant along the three segments of the intestine. The
      hypercaloric diets did not modify the general tendencies seen in the crypt and PC
      counts, but reduced the number of PCs per section in the duodenum by 50%. HC-fed,
      but not HF-fed, rats showed a similar reduction in jejunum also. These changes do
      not correlate particularly with any of the predictable effects of diet
      composition, so that a multifactorial control of PC density is proposed.

PMID- 16982479
TI  - Fractal dimension of the middle meningeal vessels: variation and evolution in
      Homo erectus, Neanderthals, and modern humans.
AB  - The middle meningeal vascular network leaves its traces on the endocranial
      surface because of the tight relationship between neurocranial development and
      brain growth. Analysing the endocast of fossil specimens, it is therefore
      possible to describe the morphology of these structures, leading inferences on
      the cerebral physiology and metabolism in extinct human groups. In this paper,
      general features of the meningeal vascular traces are described for specimens
      included in the Homo erectus, Homo neanderthalensis, and Homo sapiens hypodigms.
      The complexity of the arterial network is quantified by its fractal dimension,
      calculated through the box-counting method. Modern humans show significant
      differences from the other two taxa because of the anterior vascular dominance
      and the larger fractal dimension. Neither the fractal dimension nor the anterior
      development are merely associated with cranial size increase. Considering the
      differences between Neanderthals and modern humans, these results may be
      interpreted in terms of phylogeny, cerebral functions, or cranial structural
      network.

PMID- 16982478
TI  - Tracking the changes in unloaded bone: Morphology and gene expression.
AB  - Bone formation and growth are controlled by genetic, hormonal and biomechanical
      factors. In this study, an established rat disuse osteoporosis model, hindlimb
      suspension (HLS), was used to relate morphological change and gene expression to
      altered mechanical load in the underloaded femora and the ostensibly normally
      loaded humeri of the suspended rats (39 days old at onset; 1, 3, 7 and 14 days
      suspension). Morphological change was measured by labelling new bone formation
      with fluorescent agents during the experimental period and subsequent
      histological analysis of bone sections post-sacrifice. Hindlimb suspension
      reduced both the total amount of bone present, assessed as cross-sectional area,
      and the bone formation rate at the mid-diaphysis of the unloaded femora while no
      significant effect was found in the loaded humeri. In addition, the femora of the
      suspended animals were found to have a markedly increased circularity as a result
      of unloading. A sensitive semi-quantitative method of gene expression analysis,
      involving the creation of SMART cDNA arrays, was successfully implemented. This
      technique amplified all populations of mRNA to levels where they could be
      assessed using standard molecular biology protocols. Gene expression patterns of
      two candidate genes, c-fos and osteocalcin were assessed in periosteal tissue.
      Altered gene expression patterns were identified and tracked over the suspension
      period. The altered levels of both candidate genes were found to be consistent
      with the changes observed in the histological analysis.

PMID- 16982480
TI  - Permanently increased conductance of the murine uterine arcade after the first
      pregnancy.
AB  - Mechanical forces due to increased blood flow during the first pregnancy might
      induce a permanently higher conductance of the uterine arcade. Number of
      endothelial and smooth muscle cells, cross-sectional area and wall thickness of
      the uterine artery were measured in nulliparous mice (n = 11) and until the 93rd
      day after parturition in primiparous mice (n = 44). Inner diameter and wall area
      were calculated. Three months after the first pregnancy, uterine artery wall
      thickness was not altered compared to nulliparous mice. In contrast, inner
      diameter increased 1.6-fold, wall area 1.5-fold and the numbers of endothelial
      and smooth muscle cells increased 1.5 times. These changes were completely stable
      during the whole observation period. The increased blood flow during the first
      pregnancy might be a mandatory mechanical stimulus for uterine arcade maturation.
      This physiological maturation process could result in abortion explaining the
      higher prevalence of unexplained pregnancy losses in primiparous women.

PMID- 16982481
TI  - Undiagnosed fracture in a common foot variant: the biphalangeal little toe.
AB  - The biphalangeal little toe is an anatomical anomaly that has been previously
      well described in the early anatomical literature. But, as is the case with many
      anomalies, there is a lack of awareness of it amongst current clinicians. We
      report the case of a fracture through the distal phalanx of the little toe, with
      a delay in the diagnosis due to confusion over the X-ray findings. X-rays
      revealed a biphalangeal toe with a fracture through the distal phalanx, which
      mimicked the usual triphalangeal toe. This is the first reported case of clinical
      confusion over this anatomical variation. A review of 102 human skeletal feet at
      the Department of Anatomy, University of Melbourne, was performed to evaluate the
      frequency of the biphalangeal little toe variant, revealing an incidence of 26%.

PMID- 16982482
TI  - A mysterious something: the discovery of insulin and the 1923 Nobel Prize for
      Frederick G. Banting (1891-1941) and John J.R. Macleod (1876-1935).

PMID- 16982483
TI  - Recent advances in hyperinsulinemic hypoglycemia of infancy.
AB  - Hyperinsulinemia-induced hypoglycemia is the most common cause of persistent
      hypoglycemia in adults, children, and infants. Our understanding of the disorders
      responsible for this type of hypoglycemia has been increasing due to the recent
      discoveries in the molecular and biochemical regulation of insulin secretion. In
      this article, we review the current knowledge of the pathophysiology, clinical
      presentation, and diagnosis of disorders that cause hyperinsulinemic hypoglycemia
      of infancy. We highlight the distinction between the diffuse and focal forms of
      the disease, especially the promising results with (18)F-L-dopa positive emission
      tomography (PET) scanning for preoperative localization and distinction to guide
      the extent of surgical removal of pancreatic tissue that may result in cure
      rather than persistence of disturbed carbohydrate metabolism. CONCLUSION: Despite
      all these discoveries, much remains to be learned, as currently about one third
      of infants with hyperinsulinemic hypoglycemia have no identifiable cause.

PMID- 16982484
TI  - Repeated supratherapeutic doses of paracetamol in children--a literature review
      and suggested clinical approach.
AB  - The safety of paracetamol when given in the recommended dosage is well
      documented. However, in recent years there have been many reports of liver
      failure associated with repeated exposure to supratherapeutic doses of
      paracetamol. This paper reviews the literature on chronic supratherapeutic
      paracetamol exposure in children and the different dosing guidelines. Based on
      which, we suggest the following approach: liver injury secondary to repeated
      dosing of paracetamol should be considered when a child has received more than 75
      mg/kg/d for at least 2 d, or if risk factors for paracetamol toxicity have been
      identified. Liver transaminases, coagulation factors, and paracetamol serum
      concentrations should be measured in these children and in symptomatic children
      with vomiting, right upper quadrant abdominal pain, and jaundice who have taken
      paracetamol. Treatment with N-acetyl cysteine should be started regardless of
      paracetamol concentrations if transaminases or INR are elevated. CONCLUSION:
      Liver injury secondary to repeated dosing of paracetamol is rare but may result
      in severe morbidity and mortality. The cumulative dose of paracetamol should not
      exceed 75 mg/kg/d. Children treated with higher doses for more than 2 d should be
      evaluated for possible liver injury and treated with N-acetyl cysteine if
      evidence of liver injury is found.

PMID- 16982485
TI  - Hypothermia in the resuscitation of the neonate: a glance in my rear-view mirror.
AB  - Recent research indicates that the outcome of perinatal hypoxia-ischaemia can be
      improved by hypothermia. This was actually first observed about 40 years ago, as
      discussed in this article. Clinical application of whole-body hypothermia in the
      asphyxiated neonate showed a positive effect. Reference is made to previous
      review articles on the subject. A large experimental study indicated that the
      degree of protection against hypoxic-ischaemic damage, as judged by the
      conditioned avoidance response, was dependent on the fall in body temperature.
      The earlier reported resistance against hypothermia in the asphyxiated neonate is
      discussed and analysed. CONCLUSION: Experimental and clinical evidence suggest
      that hypothermia may be of value in resuscitation of the neonate.

PMID- 16982486
TI  - The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in
      children.
AB  - AIM: To determine the efficacy of prophylactic administration of zinc sulphate in
      reducing the occurrence of the common cold in children, and to evaluate the
      efficacy of zinc sulphate in reducing the duration and severity of cold symptoms.
      METHODS: A total of 200 healthy children were randomly assigned to receive oral
      zinc sulphate (zinc group, n=100) or placebo (placebo group, n=100). Zinc
      sulphate (15 mg of zinc) or placebo syrup were administered for prophylaxis once
      daily during a 7-mo study period. The dose was increased to two times per day (30
      mg of zinc) at the onset of cold, until symptoms resolved. RESULTS: The mean
      number of colds in the zinc group was significantly less than in the placebo
      group (1.2 vs 1.7 colds per child; p=0.003). The mean cold-related school absence
      was 0.9 d per child in the zinc group versus 1.3 d in the placebo group (p=0.04).
      Compared to the placebo group, the zinc group had shorter mean duration of cold
      symptoms and decreased total severity scores for cold symptoms (p<0.0001).
      Adverse effects were mild and similar in both groups. CONCLUSION: Zinc sulphate
      appears to be an easily administered, safe and well-tolerated alternative for the
      prevention and treatment of the common cold in children.

PMID- 16982487
TI  - Prevalence, severity and determinants of asthma in Danish five-year-olds.
AB  - BACKGROUND: The prevalence of asthma and wheeze is increasing. AIM: To study the
      annual and cumulative prevalence of asthma and wheeze in 5-y-old Danish children.
      METHODS: We obtained data on 3052 (82.0% of eligible) Danish children by a postal
      parental questionnaire including ISAAC questions regarding respiratory symptoms
      and our own questions on sociodemography and tobacco exposure. RESULTS: "Wheeze
      ever" was reported in 38.3%, "doctor-diagnosed asthma ever" in 10.5%, "childhood
      bronchitis ever" in 30.0%, "current wheeze" (<12 mo) in 19.7%, and being "severe"
      (>3 episodes) in 3.9% of the children. Current wheeze was associated with male
      gender (OR 1.63, 95% CI 1.35-1.96), low parental post-primary education (OR 1.29,
      95% CI 1.02-1.63 for <3 y vs > or =3 y) and current maternal smoking (OR 1.69,
      95% CI 1.39-2.04). "Severe current wheeze" was recognized as asthma in six and
      childhood bronchitis in three of 10 cases. Nearly all diagnosed asthmatics had
      suffered wheeze, two-thirds recently. CONCLUSION: We found a high prevalence of
      asthma and wheeze in Danish late-preschool children, associated with male gender,
      current maternal tobacco smoking and low parental post-primary education. The
      majority of children with current wheeze had an early onset, and severe early
      symptoms tended to persist. Used with consideration, the label "childhood
      bronchitis" seems purposeful.

PMID- 16982488
TI  - Sex influences on lung function and medication in childhood asthma.
AB  - AIM: To evaluate possible sex differences in prevalence, diagnosis and treatment
      of asthma, and influence on lung function associated with asthma severity in a
      population-based birth cohort (BAMSE) of 4089 children. METHODS: At 4-y follow
      up, 92% responded to a questionnaire on symptoms of asthma, current medication
      and doctor's diagnosis of asthma. A total of 2965 children participated in
      clinical testing, including measurements of peak expiratory flow (PEF), and were
      assigned to groups of asthma or no asthma by reported airway symptoms. RESULTS:
      Children in asthma groups had lower PEF readings compared to healthy children.
      This effect was most pronounced for both sexes in the persistent group (boys
      p<0.05, girls p<0.001) and for girls in the transient group (p<0.01). A doctor's
      diagnosis of asthma did not significantly differ between boys and girls, but
      significantly more boys than girls had inhaled corticosteroids, even when
      stratifying by frequency of symptoms. CONCLUSION: These results suggest that when
      4-y-old children are stratified according to common diagnostic criteria, girls
      have a larger effect on PEF of asthma symptoms and are less frequently treated
      compared to boys.

PMID- 16982489
TI  - Asthma and overweight are associated with symptoms of gastro-oesophageal reflux.
AB  - AIM: To explore the prevalence of symptoms suggestive of gastro-oesophageal
      reflux disease (GERD) in asthmatics and controls, and to control for the possible
      effect of overweight. METHODS: The prevalence of GERD symptoms was assessed using
      a questionnaire about reflux symptoms in children with asthma (n=872, mean age
      10.4 y, 65% males) compared to non-asthmatic controls (n=264, mean age 10.8 y,
      48% males), and a symptom score was calculated. The association between GERD
      symptoms and overweight (age-adjusted BMI > 25) was assessed independently.
      RESULTS: A positive reflux symptom score was found in 19.7% of the asthmatics
      compared to 8.5% of the non-asthmatic control group (odds ratio (OR) 2.6, 95% CI
      1.7-4.2). Overweight children reported GERD symptoms more frequently than
      children with normal weight (OR 1.8, 95% CI 1.2-2.6). Asthma and obesity remained
      significant predictors when analysed simultaneously by logistic regression
      analysis. One hundred and fifty-two children with asthma consented to an
      oesophageal pH study, and an abnormal pH study result (reflux index > 5.0)
      correlated positively with overweight (OR 4.9, 95% CI 2.2-11.0). CONCLUSION: The
      prevalence of symptoms associated with gastro-oesophageal reflux was increased in
      children with asthma and in overweight children. Overweight and asthma were
      independently associated with GERD symptoms, and overweight did not explain the
      higher frequency of GERD in asthma patients.

PMID- 16982490
TI  - Is paediatric assessment of motor development of very preterm and low-birthweight
      children appropriate?
AB  - AIM: To determine whether paediatricians that examine, in regular clinical
      practice, very preterm and very-low-birthweight children at 5 y of age detect
      neurological impairments and functional motor problems in these children.
      METHODS: We compared a paediatric judgement, a standardized neurological
      examination (Touwen examination) and a screening of motor development (Denver
      Developmental Screening Test; DDST) with the Movement ABC in 396 5-y-old very
      preterm and low-birthweight children. RESULTS: The Movement ABC detected
      clinically important motor disorders in 20.5% and borderline disturbances in
      22.5% of the children. Compared to the Movement ABC, the sensitivity of the
      paediatric judgement was 0.19, Touwen examination 0.62 and DDST 0.52; the
      negative predictive values were 0.61, 0.74 and 0.69, respectively. CONCLUSION:
      Paediatric assessment of motor development in 5-y-old very preterm and low
      birthweight children generally is not sensitive enough to detect functional motor
      problems. The Movement ABC should be added to the assessment of the motor
      development of very preterm and low-birthweight children at 5 y of age.

PMID- 16982491
TI  - Conclusiveness of the Cochrane Neonatal Reviews: a systematic analysis.
AB  - AIM: To assess the conclusiveness of the Cochrane Neonatal Reviews (CNRs). We
      tested the hypotheses that: 1) the majority of the reviews is inconclusive; 2)
      the majority of reviews recognizes the need for further studies; 3) the ability
      to reach a conclusion is dependent upon both the number of studies and the number
      of patients. We also aimed to determine whether the conclusiveness of the CNRs
      was affected by time. METHODS: We selected CNRs available in the Cochrane Library
      in June 2004. The number of randomized clinical trials (RCTs) found, number of
      RCTs included for analysis, number of patients enrolled, the stated need for
      further studies, and the conclusiveness of CNRs were recorded. RESULTS: Out of
      170 CNRs, 67.7% were conclusive. The average number of articles was similar, but
      the total number of patients enrolled was three times higher in the conclusive
      CNRs. The percentage of articles included in conclusive studies was significantly
      higher than in inconclusive ones. The vast majority of CNRs recognized the need
      for further studies. The number of studies included correlated significantly with
      the total number of patients included. The percentage of conclusive CNRs
      correlated negatively with year of publication. CONCLUSION: The majority of CNRs
      is conclusive, but emphasizes the need for further studies. The ability of a CNR
      to reach a conclusion is affected by the cumulative sample size and by the number
      of studies performed. The probability of a newer review to be conclusive is lower
      than that of an older review.

PMID- 16982492
TI  - Selectin polymorphisms and perinatal morbidity in low-birthweight infants.
AB  - BACKGROUND: Studies have shown an association between altered expression of
      selectins and premature birth, early sepsis and bronchopulmonary dysplasia. AIM:
      To investigate the possible link between functional polymorphisms of the E-, P-
      and L-selectin genes and perinatal morbidity. METHODS: We compared the genotype
      distribution of the E-selectin Ser128Arg, P-selectin Thr715Pro and L-selectin
      Pro213Ser polymorphisms in 125 low-birthweight singleton infants with those of
      156 healthy term neonates. We also analysed the association of genotype with risk
      of sepsis and bronchopulmonary dysplasia. RESULTS: We found no association
      between E-selectin or P-selectin polymorphisms and premature birth, nor did we
      find any association between E-selectin or P-selectin and early postnatal sepsis
      or bronchopulmonary dysplasia. Carriers of the 213Ser L-selectin allele were
      found to be more prevalent in low-birthweight infants, particularly in those with
      bronchopulmonary dysplasia. We found no association between the L-selectin
      polymorphism and early postnatal sepsis. CONCLUSION: Our results underline the
      importance of L-selectin in perinatal pathology, but further studies are needed
      to evaluate the alteration of L-selectin levels in carriers of the 213Ser allele
      and their possible contribution to premature birth and bronchopulmonary
      dysplasia.

PMID- 16982493
TI  - Values of C-reactive protein, procalcitonin, and Staphylococcus-specific PCR in
      neonatal late-onset sepsis.
AB  - AIM: To evaluate the predictive value of relevant clinical and laboratory
      parameters (complete blood count (CBC), C-reactive protein (CRP), procalcitonin
      (PCT) and Staphylococcus-specific polymerase chain reaction (PCR)) in neonates
      with suspected late-onset sepsis (LOS). METHODS: NICU neonates were prospectively
      followed for septic events. One hundred and eleven neonates developed 148
      suspected septic events beyond 3 d of age. We recorded the clinical signs and
      laboratory abnormalities at onset of sepsis, serum CRP and PCT, Staphylococcus
      specific PCR, microbiological data, and empiric antimicrobial therapy. RESULTS:
      Variables significantly associated with subsequently confirmed LOS included
      hypotension (relative risk (RR) = 5.6, 95% CI 3.29-9.53), mechanical ventilation
      (RR = 2.46, 95% CI 1.24-4.86), immature/total neutrophil ratio (I/T) > 0.2 (RR =
      5.13, 95% CI 2.54-10.31), CRP > 1.0 mg/dl (RR = 2.85, 95% CI 1.32-6.15), and
      small-for-gestational-age (SGA) status (RR = 2.13, 95% CI 1.03-4.38). PCT was not
      significantly associated with LOS. For detection of staphylococcal bacteremia,
      Staphylococcus-specific PCR showed: sensitivity 57.1%, specificity 94.7%,
      positive predictive value 53.3%, and negative predictive value 95.4%. CONCLUSION:
      Hypotension, mechanical ventilation, I/T > 0.2, CRP > 1.0 mg/dl, and SGA status
      at onset of sepsis are significant predictors of proven neonatal LOS.
      Staphylococcus-specific PCR might be of value in ruling out staphylococcal
      sepsis.

PMID- 16982494
TI  - Cord blood lipoprotein profile after magnesium sulphate treatment in pre
      eclamptic patients.
AB  - AIM: To determine lipoprotein metabolism alterations in magnesium-exposed
      neonates of women with pre-eclampsia. METHODS: The study group comprised seven
      singleton neonates of women with pre-eclampsia at term and treated with magnesium
      sulphate. Controls were 26 neonates of uncomplicated pregnancies of term
      delivery. Total serum magnesium concentrations were analysed by the photometric
      colour method. Total serum cholesterol, triglycerides and high-density
      lipoprotein cholesterol (HDL-C) levels were determined by enzymatic colour
      methods, while apoprotein (apo) A-I and apo B values were measured by
      immunoturbidimetry. Low-density lipoprotein cholesterol (LDL-C) levels were
      calculated by Friedewald's formula. Very-low-density lipoprotein cholesterol
      levels, total cholesterol/ HDL-C, apo B/apo A-I, LDL-C/apo B, LDL-C/HDL-C, and
      HDL-C/apo A-I ratios were determined by calculation. RESULTS: Magnesium levels of
      magnesium-exposed neonates were found to be 1.6 times higher than those of
      controls. Magnesium-exposed neonates had lower serum apo A-I levels, and they had
      higher apo B/apo A-I and HDL-C/apo A-I ratios when compared to controls.
      CONCLUSION: The lipoprotein profile became more atherogenic in magnesium-exposed
      neonates as it may be a potential risk factor of cardiovascular heart disease.

PMID- 16982495
TI  - Shorter hospital stay for moderately preterm infants.
AB  - AIM: To determine length of hospital stay (LOS) for moderately preterm infants
      during the last 20 years, and to identify factors affecting the number of bed
      days. METHODS: Review of LOS for all infants delivered between 30 to 34
      gestational weeks during 1983, 1988, 1993, 1998 and 2002. EXCLUSION CRITERIA:
      life-threatening abnormalities, chromosomal anomalies and death during
      hospitalization. RESULTS: 564 included infants accounted for 20% of admissions
      and 48% of bed-days in the neonatal unit. Between 1983 and 2002, maternal age and
      use of nasal continuous positive airway pressure increased, use of antibiotics
      and mechanical ventilation decreased, whereas distributions for gestational age,
      birthweight, gender, smallness for gestational age, low Apgar score or incidence
      of respiratory distress syndrome did not change. For healthy inborn singletons
      discharged home, LOS decreased from 1983 (28+/-11 d, mean+/-SD values) to 2002
      (14+/-7 d, p<0.05). Infants born more immature had longer LOS, but
      postconceptional age at discharge did not differ between age groups. CONCLUSION:
      LOS for moderately preterm infants has decreased as a result of individualized
      neonatal care and organization of homecare support. Shorter LOS is of benefit to
      the family, prevents overcrowding in the NICU and has important economic
      implications.

PMID- 16982496
TI  - Intimal thickness of the coronary arteries in low-birthweight infants.
AB  - BACKGROUND: Intimal thickening is considered to be an early manifestation of
      developing atherosclerosis in healthy young adults and children. Low birthweight
      correlates with increased incidence of cardiovascular diseases. AIM: To test the
      hypothesis that low birthweight is associated with relatively thickened intima at
      birth. METHODS: The coronary arteries of 175 children were screened from serial
      cross-sections for maximal intimal thickening and measured morphometrically. The
      area of intima and media and the length of internal elastic lamina were measured.
      The intimal to medial area ratio and calculated thicknesses of intima were used
      in statistical comparisons. Only children who died within 30 d after birth
      (n=111) were included. RESULTS: There was a significant positive correlation
      between intimal thickness and birthweight in low-birthweight children (p<0.006).
      Neither the relative thickness of the intima nor the ratio of intimal to medial
      area increased with increasing growth restriction. The sum of the thicknesses of
      arterial media and intima had a significant positive correlation with birthweight
      in these infants. CONCLUSION: Intimal thickness present at birth in small-for
      date children does not seem to be an aetiological factor for the increased risk
      of coronary heart disease later in life.

PMID- 16982497
TI  - Gender differences in neurodevelopmental outcomes among extremely preterm,
      extremely-low-birthweight infants.
AB  - AIM: To determine whether gender-specific responses to perinatal and neonatal
      events and exposures explain the male disadvantage in early childhood outcomes.
      METHODS: Infants were in the National Institute of Child Health and Human
      Development (NICHD) Neonatal Research Network, born 1/1/1997-12/31/2000, <28 wk,
      with neurodevelopmental follow-up at 18-22 mo corrected age. We evaluated and
      compared univariate and multivariate associations of risk factors with
      neurodevelopmental outcomes for girls and boys. Neurodevelopmental impairment
      (NDI) was one or more of the following: moderate--severe cerebral palsy (CP),
      Bayley Mental (MDI) or Psychomotor (PDI) Development Indices <70, deafness or
      blindness. RESULTS: Boys (n=1216) were more likely than girls (n=1337) to have
      adverse outcomes (moderate--severe CP: 10.7% vs 7.3%; MDI < 70: 41.9% vs 27.1%;
      NDI: 48.1% vs 34.1%). Major risk factors were also more common in boys.
      Independent multivariate associations of risk factors with outcome differed by
      gender, but not consistently in favor of girls. In multivariate models including
      both girls and boys, male gender remained an independent risk factor for MDI < 70
      (2.0, 95% CI 1.6-2.5) and NDI (1.8, 95% CI 1.5-2.2). CONCLUSION: Perinatal,
      neonatal and early childhood factors confer similar incremental risk or
      protection to boys and girls, but boys appear to have inherently greater baseline
      risk. Unmeasured biological variables likely contribute to the preterm male
      neurodevelopmental outcome disadvantage.

PMID- 16982498
TI  - Development and behaviour of low-birthweight term infants at 8 years in northeast
      Brazil: a longitudinal study.
AB  - AIM: To investigate the development and behaviour of low-birthweight (LBW) term
      infants compared with matched term infants of appropriate birthweight (ABW).
      METHODS: Two parallel cohorts of LBW infants (1500-2499 g) and ABW controls (3000
      3499 g) were enrolled at birth in northeast Brazil. At 8 y, 164 children were
      assessed using clinical and psychological tests. RESULTS: The LBW group had lower
      IQ scores than ABW children on the Weschler Intelligence Scale for Children;
      differences were larger on the performance (5 points, p = 0.04) than the verbal
      scale (3 points, p = 0.11). LBW children had poorer dynamic balance (p = 0.03)
      and eye-hand coordination (p = 0.02), but better selective attention (p = 0.02).
      Hyperactivity and conduct problems were common in both groups, but fewer LBW
      children had peer problems (p = 0.04). After controlling for social background,
      IQ was not significantly associated with birthweight (p = 0.10). Significant
      determinants were maternal education, home stimulation and type of school
      attended. The effect of birthweight on coordination and selective attention
      remained significant. Birth head circumference and growth in head size in the
      first 6 mo had independent effects on IQ. CONCLUSION: After controlling for
      social background, LBW term infants did not differ from ABW infants in cognition
      at school age. Head circumference at birth and 6 mo was a better predictor than
      birthweight of IQ.

PMID- 16982499
TI  - Effect of a six-month training programme on the physical capacities of Romanian
      schoolchildren.
AB  - AIM: To analyze the effects of a training programme on the motor performance of
      Romanian schoolchildren. METHODS: A total of 178 boys (9.5+/-0.8 y, 34+/-9 kg,
      137.6+/-8 cm) and 192 girls (9.6+/-0.4 y, 32.7+/-7.6 kg, 136.9+/-7.5 cm) were
      randomly selected for the training group (TG) (n=198, 109 girls, 89 boys) and
      control group (CG) (n=172, 83 girls, 89 boys). The TG completed a 6-mo
      extracurricular training programme (two 50-min sessions per week) involving
      moderate-intensity impact exercises. At baseline and at follow-up, the EUROFIT
      tests were administered, and body composition, skeletal maturation and BMI were
      calculated. RESULTS: At baseline there were no differences in physical
      characteristics between TG and CG. With the exception of cardiorespiratory
      endurance, both groups improved motor performances at follow-up. However, for TG
      boys the improvement was greater than for CG boys in the plate-tapping (+37.2%),
      sit-up (+20.4%), standing broad-jump (+13%) and shuttle-run tests (+3.8%). TG
      girls improved more than CG girls only in the standing broad-jump (+18.8%) and
      shuttle-run (+8.5%) tests. CONCLUSION: Boys and girls in trained groups
      demonstrated greater increases in some tests of motor performance compared to
      their untrained peers. Two extra sessions of physical education per week were
      sufficient to elicit improvements in a number of components of motor fitness.

PMID- 16982500
TI  - The frequency of vitamin D insufficiency in healthy female adolescents.
AB  - AIM: To establish the frequency and causes of vitamin D insufficiency in healthy
      female adolescents in Izmir, Turkey. METHODS: 64 adolescents from a low--(Ikinci
      Inonu) and a high--(Ilica) socio-economic settlement were included. Parents'
      monthly income was classified as low, middle and high. The blood samples were
      drawn at the end of the summer and winter periods. RESULTS: Vitamin D
      insufficiency percentages for the end-of-winter period were 59.4% in Ikinci Inonu
      and 15.6% in Ilica, and for the end of summer 25% and 15.6%, respectively.
      Calcidiol levels of cases from Ikinci Inonu were found to be lower compared with
      the levels of cases from Ilica (34+/-15 vs 59+/-24 nmol/l for end of winter,
      p=0.000; 51+/-22 vs 65+/-28 nmol/l for end of summer, p=0.03). Calcidiol levels
      of cases whose parental monthly income was low and whose mothers were illiterate
      were significantly lower than the others (48+/-18 vs 65+/-29 nmol/l for end of
      summer, p=0.01; 33+/-16 vs 56+/-23 nmol/l for end of winter, p=0.000; 45+/-13 vs
      64+/-29 nmol/l for end of summer, p=0.007; 36+/-17 vs 51+/-25 nmol/l for end of
      winter, p=0.02; respectively). CONCLUSION: Vitamin D insufficiency was frequent,
      especially in the end-of-winter period. Basic risk factors were low socio
      economic status, illiteracy of mothers and low calcium intake.

PMID- 16982501
TI  - The prevalence of unwanted and unlawful sexual experiences reported by Danish
      adolescents: results from a national youth survey in 2002.
AB  - AIM: To obtain current data about child sexual abuse in Denmark and to assess
      abused children's own perception of early sexual experiences, which are unlawful
      according to the Danish Penal Code. METHODS: Multimedia computer-based self
      administered questionnaires (CASI) were completed by a national representative
      sample of 15-16-y-olds. Child sexual abuse was defined according to the penal
      code and measured by questions defining specific sexual activities, the
      relationship between the older person and the child, and the youth's own
      perception of the incident. RESULTS: Among 5829 respondents, 11% reported
      unlawful sexual experiences, 7% of boys and 16% of girls. Only 1% of boys and 4%
      of girls felt that they "definitely" or "maybe" had been sexually abused.
      CONCLUSION: A relatively high percentage of Danish adolescents have early,
      unlawful sexual experiences. However, young people's own perception of sexual
      abuse tends to differ from that of the authorities, or their tolerance of abusive
      incidents is high. Gender differences were found in factors predicting perception
      of abuse.

PMID- 16982502
TI  - Neuromuscular function and balance of prepubertal and pubertal blind and sighted
      boys.
AB  - AIM: To compare the neuromuscular function and balance of blind prepuberty- and
      puberty-aged boys to those with normal sight. METHODS: Thirty-three prepubertal
      (aged 9-13 y) and pubertal (aged 15-18 y) blind and sighted boys were tested for
      muscle mass thickness, electromyography and maximal isometric strength, dynamic
      explosive actions, and balance. RESULTS: There was no difference in the muscle
      mass thickness, maximal strength or vertical jump between the blind and sighted
      boys. However, fitness-ball throwing and five-jump distances were significantly
      shorter in both blind groups compared to the sighted groups. One-leg stance of
      the prepuberty-aged sighted boys was 109 (67) s and in blind boys 32 (12) s, and
      in the puberty-aged boys 120 (57) s and 31 (8) s, respectively. When vision was
      blocked in the sighted boys, differences between the blind and sighted boys
      disappeared. CONCLUSION: The results showed comparable performance between
      prepubertal and pubertal blind and sighted boys in the static physical fitness
      tests. However, balance and performance in dynamic multi-joint tests did not
      improve similarly in the blind groups compared to sighted groups, indicating that
      maturation, learning and experience by themselves cannot compensate for the loss
      of sight.

PMID- 16982503
TI  - Recurrence of brain tumours in patients treated with growth hormone: analysis of
      KIGS (Pfizer International Growth Database).
AB  - BACKGROUND: Growth hormone (GH) has been used successfully in the treatment of
      short stature secondary to GH deficiency in survivors of childhood brain tumours.
      There has been concern that GH might increase the risk of recurrence. AIM: To
      analyse KIGS (Pfizer International Growth Database) with respect to tumour
      recurrence in patients with brain tumours. METHODS: Data for tumour recurrence
      were analysed retrospectively in 1038 patients with craniopharyngiomas, 655 with
      medulloblastomas, 113 with ependymomas, 297 with germinomas, and 400 with
      astrocytomas or gliomas. All patients had received recombinant human GH
      (Genotropin, Pfizer Inc.). RESULTS: Recurrence-free survival rates were 63% at a
      follow-up of 10.3 y in craniopharyngioma, 69% in 9.1 y in the glial tumours, 71%
      in 7.4 y in germinomas, 92% in 4.6 y in medulloblastomas and 89% in 2.5 y in
      ependymomas. Dose of GH and treatment modalities did not differ significantly
      between patients with and without recurrence. CONCLUSION: Tumour recurrence rates
      in surviving patients with brain tumours receiving GH treatment do not appear to
      be increased compared with published reports. However, longer follow-up regarding
      recurrences and secondary neoplasms remains essential.

PMID- 16982504
TI  - Bone mineral density is reduced in brain tumour patients treated in childhood.
AB  - AIM: To determine the prevalence of low bone mineral density among children
      surviving brain tumours and to identify possible factors underlying impaired bone
      health. METHODS: Cross-sectional study; total body bone mineral density (TBBMD),
      fat mass (FM) and lean body mass (LBM) were measured by dual-energy X-ray
      absorptiometry (DXA) in 46 brain tumour patients aged from 3.8 to 28.7 y (mean
      14.9 y) treated in childhood 1.4-14.8 y (mean 6.4 y) after end of treatment for
      brain tumour. Low bone mineral density was defined as TBBMD z score < - 2.0.
      RESULTS: Fifteen patients had TBBMD z scores < - 2.0, indicating a 33% prevalence
      of low bone density. The TBBMD z score ranged from -5.7 to 0.6 (mean -1.7). Out
      of several potential factors, only combined craniospinal irradiation was
      significantly associated with low z score (p=0.034, according to multiple
      regression analysis), while exclusive cranial irradiation showed a borderline
      statistical association (p=0.100, according to multiple regression analysis).
      CONCLUSION: One third of brain tumour patients treated in childhood had reduced
      bone mineral density. The reasons for this condition are apparently
      multifactorial, including craniospinal irradiation.

PMID- 16982505
TI  - Cathepsin K expression is diminished in infants with bronchopulmonary dysplasia.
AB  - The expression of a potent collagenolytic enzyme, cathepsin K, was measured in
      repeated tracheal aspirate samples from premature infants with and without a
      chronic lung disorder, bronchopulmonary dysplasia (BPD). At 9--13 d, but not
      before, cathepsin K expression was significantly lower in the lungs of premature
      infants developing BPD. CONCLUSION: Insufficient pulmonary cathepsin K in BPD may
      predispose premature lungs to pulmonary fibrosis.

PMID- 16982506
TI  - Early detection of infant hearing loss: current experiences of health
      professionals in a developing country.
AB  - AIM AND METHODS: To investigate the experiences of doctors and nurses in infant
      hearing loss through an open-ended questionnaire in Lagos, Nigeria. RESULTS: Few
      respondents detected children with hearing loss within the first 6 mo of life.
      Parental concern was the most significant lead for doctors. Children suspected of
      hearing loss were often referred to ENT surgeons before objective hearing
      evaluation was conducted. CONCLUSION: Doctors and nurses should routinely seek
      objective infant hearing assessment for timely detection of permanent hearing
      loss.

PMID- 16982507
TI  - Ex utero intrapartum treatment (EXIT) for congenital giant ranula.
AB  - Congenital giant ranula causing life-threatening upper airway obstruction is a
      rare condition. A well-planned ex utero intrapartum treatment (EXIT) procedure
      for aspiration and decompression of the cystic lesion is simple, efficacious and
      effective in securing a patent airway before the fetus is completely delivered,
      and may prevent lifelong neurodevelopmental complications associated with
      perinatal asphyxia in such cases. CONCLUSION: EXIT could be a life-saving
      procedure for congenital giant ranula.

PMID- 16982508
TI  - Fast improvement of verbal memory function after left temporal tumour resection.
AB  - CASE REPORT: A 7-y-old, right-handed girl presented at our clinic with complex
      partial seizures, behavioural problems and word-finding difficulties. Clinical
      examination was normal, but electroencephalogram revealed bilateral epileptic
      discharges in the temporal and paracentral leads. Magnetic resonance imaging
      showed an intracerebral mass in the left mesial temporal lobe in the areas of the
      gyrus temporooccipitalis medialis and gyrus parahippocampalis. Neuropsychological
      testing brought to light an above-average general intelligence, but the girl
      performed below average in verbal memory tests and average in figural memory
      tests. RESULTS: The tumour was completely removed by surgery. Neuropsychological
      testing 3 and 11 wk after tumour resection demonstrated above-average verbal
      learning and memory abilities and improved visual memory. The emotional
      disturbances, seizures and electroencephalogram abnormalities disappeared
      completely during the postoperative follow-up. CONCLUSION: After resection of a
      left temporal brain tumour, the patient was free of seizures, and
      neuropsychological functions recovered completely within weeks.

PMID- 16982509
TI  - Vasopressin in catecholamine-resistant septic and cardiogenic shock in very-low
      birthweight infants.
AB  - AIM: To evaluate vasopressin as a rescue therapy in catecholamine-refractory
      septic and cardiogenic shock in very-low-birthweight (VLBW) infants. METHODS:
      Prospective assessment of vasopressin therapy in three VLBW infants with
      catecholamine-refractory septic shock (24 + 6 wk, 600 g) and cardiogenic shock
      (26 + 1 wk, 890 g; 26 + 1 wk, 880 g) at a university hospital. RESULTS: Adequate
      systemic arterial blood pressure could only be restored after vasopressin
      administration as a continuous infusion over a 36-h period in the preterm
      suffering from septic shock; in the two neonates with cardiogenic shock, only a
      transient stabilization in mean arterial pressure was observed, which did not
      impact on the poor prognosis. CONCLUSION: Although vasopressin appears to be a
      suitable rescue therapy in catecholamine-resistant septic shock in VLBW infants,
      further evaluation in controlled clinical trials is warranted.

PMID- 16982510
TI  - Circulating adiponectin levels in Kawasaki disease.
AB  - AIM: To investigate the kinetics of adipocytokine in Kawasaki disease (KD).
      METHODS: The plasma levels of adiponectin, IL-6 and TNF-alpha were measured in 20
      patients with KD, 15 patients with acute febrile diseases (disease control, DC)
      and 15 healthy children (HC). RESULTS: Plasma adiponectin levels in patients with
      acute KD were significantly lower (p < 0.01) than those with convalescent KD, DC
      and HC. The decreased levels of adiponectin negatively correlated with the
      increased levels of CRP and IL-6 in acute KD. CONCLUSION: Hypoadiponectinaemia
      was shown during the acute phase of KD vasculitis. The downregulation of
      adiponectin secreted from adipose tissue may be closely linked to upregulation of
      systemic pro-inflammatory markers in acute KD.

PMID- 16982511
TI  - On transient breastfeeding-related chylomicronaemia syndrome.
AB  - This paper reports on two male infants with abnormally high levels of serum
      triacylglycerols (>15.00 mmol/l) and massive accumulation of chylomicrons.
      Pathological lipidograms were observed during breastfeeding only and were typical
      of a rare chylomicronaemia syndrome. Laboratory abnormalities were detected
      accidentally in the otherwise healthy infants. An unrecognized modulating factor
      in fresh mother's milk caused transitory decreased activity of hydrolytic complex
      for chylomicrons and very-low-density lipoproteins, probably due to a dysfunction
      of lipoprotein lipase. The normalization of lipidograms suggested that the
      catalytic activity of lipoprotein lipase rapidly recovered after weaning.
      Pathogenesis moved more towards an immune disorder, to the production of
      (auto)antibodies against a component of the lipolytic system. Mother's milk
      should be substituted with banked donor human milk, but this is not an
      unambiguous demand. CONCLUSION: Fresh mother's milk caused a decrease in the
      activity of lipolytic enzyme (lipoprotein lipase). The massive
      hypertriacylglycerolaemia quickly disappeared after weaning. Two infants with
      this transient chylomicronaemia syndrome were asymptomatic.

PMID- 16982512
TI  - Painful rash and swelling of the limbs after recurrent infections in a teenager:
      polyarteritis nodosa.
AB  - Polyarteritis nodosa is a rare disease in childhood and adolescence that is
      difficult to diagnose clinically. We report on a 17-y-old girl presenting with a
      history of recurrent infections of the upper respiratory tract and conjunctivitis
      followed by a painful rash on the upper and lower extremities resembling erythema
      nodosum. The diagnosis of polyarteritis nodosa was proven by skin biopsy. Therapy
      with intravenous immunoglobulins failed, but with systemic steroids she responded
      promptly. CONCLUSION: Polyarteritis nodosa is a differential diagnosis in
      adolescents presenting with fever and an erythema nodosum-like rash.

PMID- 16982513
TI  - Case 1: Acute abdomen following submandibular swelling in a girl.

PMID- 16982514
TI  - Case 2: Suspected non-accidental injury.

PMID- 16982515
TI  - Case 3: A neonate with an abdominal mass.

PMID- 16982516
TI  - Formation of iodoacetic acids during cooking: interaction of iodized table salt
      with chlorinated drinking water.
AB  - Iodoacetic and chloroiodoacetic acids were formed when municipal chlorinated tap
      water was allowed to react with iodized (with potassium iodide) table salt or
      with potassium iodide itself. Iodoacetic acid was recently shown to be a potent
      cytotoxic and genotoxic agent. For analysis, samples were extracted with t-amyl
      methyl ether and converted to the corresponding methyl esters using methanol and
      sulfuric acid. The concentration of iodoacetic acid was determined by gas
      chromatography-mass spectrometry (GC-MS) using an authentic standard. The
      identities of iodoacetic and chloroiodoacetic acids were further confirmed by gas
      chromatography-high-resolution mass spectrometry (GC-HRMS). Certain influences of
      sodium hypochlorite and humic acid as well as the concentration of potassium
      iodide on the yields of these acids were investigated. The concentration of
      iodoacetic acid in tap water samples boiled with 2 g l-1 of iodized table salt
      was found to be in the 1.5 microg l-1 range, whilst the concentration of
      chloroiodoacetic acid was estimated to be three to five times lower.

PMID- 16982517
TI  - Supercritical fluid extraction (SFE) of 4(5)-methylimidazole (4-MeI) and 2-acetyl
      4(5)-(1,2,3,4)-tetrahydroxybutyl-imidazole (THI) from ground-coffee with high
      performance liquid chromatographic-electrospray mass spectrometric quantification
      (HPLC/ESI-MS).
AB  - Two polar analytes, 4(5)-methylimidazole (4-MeI) and 2-acetyl-4(5)-(1,2,3,4)
      tetrahydroxybutyl-imidazole (THI), were extracted with supercritical carbon
      dioxide (CO2) modified with aqueous methanol. The method was applied to a roasted
      coffee powder with good recovery rates. Method efficiency was compared with that
      of solid-phase extraction using SCX Disc cartridges and validated for spiked
      solid matrix. The analytes were determined using isocratic liquid chromatography
      mass spectrometry (LC/MS) on an Atlantis HILIC Silica column (150 x 2.1 mm, 3
      microm) with 80% methanol and 20% 0.01 mol l-1 ammonium formate as the mobile
      phase. The limit of quantification was around 1.5 pg for 4-MeI and 2.0 pg for
      THI. The linearity of the calibration curves was satisfactory as indicated by
      correlation coefficients of >0.999. The coefficient of variation for the intra
      day and inter-day precisions was <4% (n = 6). Accuracy was in the range 98-101%;
      recovery rates were > or = 98 and > or = 99% for THI and 4-MeI, respectively.
      Several samples of Arabica coffee from various locations and commercially
      available 'off-the-shelf' coffee products (Arabica/Robusta mixtures) were
      analysed to test the method.

PMID- 16982518
TI  - Evidence that urinary excretion of thiouracil in adult bovine submitted to a
      cruciferous diet can give erroneous indications of the possible illegal use of
      thyrostats in meat production.
AB  - Thyrostats have been banned for use as veterinary drugs in Europe since 1981
      because of their carcinogenic and teratogenic properties. Until now, the
      identification of thiouracil in animal biological matrices has been interpreted
      as the consequence of an illegal administration. The present paper studies the
      influence of a cruciferous-based feed on the occurrence of thiouracil as a
      residue in urine. Urine samples collected from two heifers fed on cabbage or
      rapeseed cakes were analysed for the presence of thiouracil by 3
      iodobenzylbromide derivatization and liquid chromatography-electrospray
      ionization tandem mass spectroscopy (LC-ESI(-)-MS/MS) analysis. Urine collected
      after cabbage or rapeseed feeding showed thiouracil concentrations in the range 3
      7 and 2-9 microg l-1, respectively, demonstrating a relationship between a diet
      based on cruciferous vegetables and the occurrence of thiouracil in urine.
      Thiouracil was excreted in urine in the hours following cruciferous intake.
      Complete elimination (<0.8 microg l-1) of the compound occurred within 5 days.
      The precursors in cruciferous vegetables responsible for the thiouracil excretion
      in urine were proved not to be thiouracil itself.

PMID- 16982519
TI  - Novel approach to control sulfamethazine misuse in food-producing animals by hair
      analysis.
AB  - The presence of sulfamethazine residues in pig and calf hair was compared with
      the residual levels encountered in the corresponding edible tissues (liver and
      muscle) as a consequence of drug administration. Sulfamethazine up to 84.7 mg kg
      1 was found in calf hair samples after a pharmacological treatment, with a
      significant effect of hair pigmentation. High concentrations of the parent drug
      were detected in calf hair for 4 weeks after administration, when sulfamethazine
      residues were no longer detectable in the corresponding edible tissues. In a
      similar way, pig hair also accumulated sulfamethazine residues up to 40.5 mg kg
      1, which was more than the amount detected in the corresponding muscle and liver
      samples at slaughter. Hair analysis seems a suitable tool to improve the efficacy
      of regulatory controls, and thus the safety of the food chain and to discourage
      the improper use of sulfamethazine in animal farming.

PMID- 16982520
TI  - Effect of cooking on enrofloxacin residues in chicken tissue.
AB  - The aim of this study was to determine the effect of different cooking processes
      (microwaving, roasting, boiling, grilling and frying) on naturally incurred
      enrofloxacin residues in chicken muscle. Enrofloxacin and its metabolite,
      ciprofloxacin, were analysed using a validated LC-MS method with limits of
      detection (LOD) and quantification (LOQ), respectively, of 2 and 5 ng g-1
      quinolones in muscle samples. The method was shown to be linear over the range 5
      500 ng g-1. Mean intra-day relative standard deviation (RSD) at a concentration
      of 50 ng g-1 (n = 6) was 6%; inter-day RSD was 12%. A recovery study demonstrated
      that 65-101%, of the drug and metabolite could be recovered from the tissue. The
      RSD with naturally incurred roasted chicken breast was 9.18% at a concentration
      of 11 +/- 1.01 ng g-1 (n = 6). In water, enrofloxacin remained stable for 3 h
      when heated at 100 degrees C. It was concluded that residue data from raw tissue
      are valid for estimation of consumer exposure to this drug, as well as the ADI
      calculations because cooking procedures did not affect enrofloxacin residues,
      which remained stable during heating. However, there was an apparent decrease in
      quinolone concentration in tissue because some was lost by exudation into the
      liquid used for cooking. Conversely, for a cooking procedure with water loss,
      there was an apparent increase in residue concentration.

PMID- 16982521
TI  - Rate of degradation of lambda-cyhalothrin and methomyl in grapes (Vitis vinifera
      L.).
AB  - Rates of degradation of lambda-cyhalothrin and methomyl residues in grape are
      reported. The dissipation behavior of both insecticides followed first-order rate
      kinetics with similar patterns at standard and double-dose applications. Residues
      of lambda-cyhalothrin were lost with pre-harvest intervals (PHI) of 12.0-12.5 and
      15.0-15.5 days, corresponding to the applications at 25 and 50 g a.i. ha-1,
      respectively. In the case of methomyl, residues were lost with PHI of 55.0 and
      61.0 days, following applications at 1 and 2 kg a.i. ha-1, respectively. The PHI,
      recommended on the basis of the experimental results, was shown to be effective
      in minimizing residue load of these insecticides below their maximum residue
      limits (MRLs) in vineyard samples.

PMID- 16982522
TI  - Co-occurrence of aflatoxin B1, fumonisin B1, ochratoxin A and zearalenone in
      cereals and peanuts from Cote d'Ivoire.
AB  - This survey examined 30 samples of rice (n = 10), maize (n = 10) and peanuts (n =
      10) from Cote d'Ivoire for aflatoxin B1, fumonisin B1 and zearalenone using
      immunoassays, and ochratoxin A using a validated HPLC method with fluorescence
      detection. In Cote d'Ivoire, as in other countries, several mycotoxins are
      present in the same commodities. These mycotoxins are from different structural
      families: aflatoxin B1, fumonisin B1, zearalenone and ochratoxin A, normally
      produced by fungal species from Aspergillus, Penicillium and Fusarium genera.
      Some samples contained four mycotoxins (86%). Four peanuts samples did not show
      ochratoxin A (14%), whereas they contained aflatoxin B1 concentrations above the
      EU regulatory limits. Concentrations of ochratoxin A, zearalenone and fumonisin
      B1 were low and may not cause problems per se; however, fears remain that the
      tolerable daily intake may be exceeded due to eating habits and synergistic
      effects could be important with the combination of several mycotoxins.
      Investigations in this direction are underway, together with isolation and
      characterization of the fungal species involved.

PMID- 16982523
TI  - Effects of Fusarium toxin-contaminated wheat and feed intake level on the
      biotransformation and carry-over of deoxynivalenol in dairy cows.
AB  - An experiment was carried out to examine the effects of feeding Fusarium toxin
      contaminated wheat (8.21 mg deoxynivalenol (DON) and 0.09 mg zearalenone (ZON)
      per kg dry matter) at different feed intake levels on the biotransformation and
      carry-over of DON in dairy cows. For this purpose, 14 ruminal and duodenal
      fistulated dairy cows were fed a diet containing 60% concentrate with a wheat
      portion of 55% (Fusarium toxin-contaminated wheat (mycotoxin period) or control
      wheat (control period)) and the ration was completed with maize- and grass silage
      (50 : 50) on a dry matter basis. Daily DON intakes ranged from 16.6 to 75.6 mg in
      the mycotoxin period at dry matter intakes of 5.6-20.5 kg. DON was almost
      completely biotransformed to de-epoxy DON (94-99%) independent of the DON/feed
      intake, and the flow of DON and de-epoxy DON at the duodenum related to DON
      intake ranged from 12 to 77% when the Fusarium toxin-contaminated wheat was fed.
      In the serum samples, de-epoxy DON was detected in the range of 4-28 ng ml-1 in
      the mycotoxin period, while concentrations of DON were all below the detection
      limit. The daily excretion of DON and de-epoxy DON in the milk of cows fed the
      contaminated wheat varied between 1 and 10 microg and between 14 and 104 microg,
      respectively. The total carry-over rates as the ratio between the daily excretion
      of DON and de-epoxy DON into milk and DON intake were in the ranges of 0.0001
      0.0002 and 0.0004-0.0024, respectively. Total carry-over rates of DON as DON and
      de-epoxy DON into the milk increased significantly with increasing milk yield. In
      the urine samples, de-epoxy DON was the predominant substance as compared with
      DON with a portion of the total DON plus de-epoxy DON concentration to 96% when
      the Fusarium toxin-contaminated wheat was fed, whereas the total residues of DON
      plus de-epoxy DON in faeces ranged between 2 and 18% of DON intake in the
      mycotoxin period. The degree of glucuronidation of de-epoxy DON was found to be
      approximately 100% in serum. From 33 to 80% of DON and from 73 to 92% of de-epoxy
      DON, and from 21 to 92% of DON and from 86 to 100% of de-epoxy DON were
      glucuronidated in the milk and urine, respectively. It is concluded that DON is
      very rapidly biotransformed to de-epoxy DON in the rumen and only negligible
      amounts of DON and de-epoxy DON were transmitted into the milk within the range
      of 5.6-20.5 kg day-1 dry matter intake and milk yields (fat corrected milk)
      between 10 and 42 kg day-1.

PMID- 16982524
TI  - Impact of fungicides on Aspergillus carbonarius growth and ochratoxin A
      production on synthetic grape-like medium and on grapes.
AB  - A study was undertaken to evaluate the impact of the application of several
      fungicide treatments used in Spanish vines on Aspergillus carbonarius growth and
      ochratoxin A production. Three trials were designed in order: (1) to screen 26
      fungicides at the doses recommended by manufacturers on grape-like synthetic
      medium at 20 and 30 degrees C; (2) to find out the minimum inhibitory
      concentration of each fungicide for A. carbonarius growth on synthetic medium;
      and (3) to investigate the effect of several fungicides on A. carbonarius
      inoculated grapes. In synthetic medium nine fungicides significantly reduced A.
      carbonarius growth rate. Meanwhile, 13 fungicides completely inhibited its
      growth. In general, growth was faster at 30 degrees C than at 20 degrees C,
      contrary to ochratoxin A production. Fungicides that stopped fungal growth also
      inhibited ochratoxin A production, but not all the fungicides that reduced growth
      reduced the ochratoxin A synthesis. In general, fungicides that contained copper
      or strobilurins reduced both growth and ochratoxin A production, contrary to
      sulphur fungicides. At the optimum temperature for A. carbonarius growth of 30
      degrees C, higher amounts of fungicide were needed to prevent fungal growth than
      at 20 degrees C. Among the fungicides that inhibited A. carbonarius growth on
      synthetic medium at the initial doses, cyprodinil seemed to be the active
      ingredient more effective at stopping fungal growth when testing reduced doses.
      The fungicide effect on grapes was similar to that on synthetic medium. Both
      infection and ochratoxin A production were reduced when using cyprodinil (37.5%)
      plus fludioxonil (25%) and azoxystrobin (25%). Penconazole (10%) also showed a
      clear reduction in ochratoxin A production at both temperatures, although
      infection was only reduced at 20 degrees C. Ochratoxin A reduction was strain and
      temperature-dependent. In general, fenhexamid (50%), mancozeb (80%) and copper
      hydroxide (80%) plus copper (50%) enhanced infection and ochratoxin A production.

PMID- 16982525
TI  - Identification of organic contaminants in disposable aluminium foil containers.
AB  - A series of disposable aluminium foil containers designed for cooking and
      packaging foods and available on the Italian market were investigated. Using
      different analytical techniques (near infrared (NIR), High Resolution Gas
      Chromatography (HRGC), gas chromatography/mass spectrometry (GC/MS)), organic
      substances used as lubricants in the manufacturing of the containers were
      detected on the aluminium layer in contact with the food. These contaminants were
      not mineral hydrocarbon fractions used for the shaping of can lids and bodies,
      but had an organic structure identifiable as esters derived by synthesis between
      fatty acids C8 and C10 with glycerine, and between C16 and C18 with butyl
      alcohol. Mixtures of higher esters were also identified as contaminants. Twelve
      samples were analysed, and the total amount of contaminant substances was found
      to range from 900 to 1200 microg dm-2. It is recommended, for safety and
      compliance with European Community (EC) Regulation No. 1935/2004 (27 October
      2004), that the use of aluminium foil containers be subject to appropriate
      regulation concerning substances adopted for technological purposes.

PMID- 16982526
TI  - Modelling of migration from multi-layers and functional barriers: estimation of
      parameters.
AB  - Functional barriers form parts of multi-layer packaging materials, which are
      deemed to protect the food from migration of a broad range of contaminants, e.g.
      those associated with reused packaging. Often, neither the presence nor the
      identity of the contaminants is known, so that safety assessment of the materials
      has to rely on predictive tools. Several complementary freeware described here
      allow one to model diffusion in multi-layer films. These tools require the input
      of parameters that are not easy to determine or predict. Previous work has
      focused on the prediction of diffusion coefficients at storage temperatures of
      packaging in contact with food. However, many other kinetic and thermodynamic
      parameters are needed to describe transport properties during the processing of a
      material at high temperature and during its shelf-life. All parameters needed for
      the calculations are discussed. In order to propose default values, the approach
      consists of (1) reviewing the available literature data, (2) running experiments
      on polypropylene, polyethylene and poly(ethylene vinyl alcohol) in typical
      conditions (separately diffusion during processing and migration) and (3)
      simulating numerical sets for typical situations. Several freeware are proposed
      to simulate migration from multi-layers and functional barriers using the default
      parameters.

PMID- 16982529
TI  - Particulate air pollution from bushfires: human exposure and possible health
      effects.
AB  - Toxicological studies have implicated trace metals adsorbed onto airborne
      particles as possible contributors to respiratory and/or cardiovascular
      inflammation. In particular, the water-soluble metal content is considered to be
      a harmful component of airborne particulate matter. In this work, the trace metal
      characteristics of airborne particulate matter, PM2.5, collected in Singapore
      from February to March 2005 were investigated with specific reference to their
      bioavailability. PM2.5 mass concentrations varied between 20.9 mug/m3 and 46.3
      microg/m3 with an average mass of 32.8 microg/m3. During the sampling period,
      there were several bushfires in Singapore that contributed to sporadic increases
      in the particulate air pollution, accompanied by an acrid smell and asthma
      related allergies. The aerosol samples were subjected to analysis of trace
      elements for determining their total concentrations as well as their water
      soluble fractions. Our results showed an increase in concentration of several
      water-soluble trace metals during bushfires compared to their urban background
      levels in Singapore. In order to measure the human exposure to particulate air
      pollution, the daily respiratory uptake (DRU) of several trace metals was
      calculated and compared between haze and nonhaze periods. The DRU values were
      significantly higher for several metals, including Zn, Cu, and Fe, during
      bushfires. Electron paramagnetic resonance (EPR) measurements showed that the
      particulate samples collected during bush fires generate more toxic hydroxyl
      radicals (OH.) than those in the background air, due to the presence of more
      soluble iron ions.

PMID- 16982530
TI  - Assessing exposure to diesel exhaust particles: a case study.
AB  - The assessment of the vehicular contributions to urban pollution levels is of
      particular importance given the current interest in the possible adverse health
      effects. This study focused on human exposure to diesel-engine-derived
      particulate matter. Diesel vehicles are known to emit fine particulate matter
      (PM2.5) containing carcinogens such as polycyclic aromatic hydrocarbons (PAHs),
      and have therefore received considerable attention. In this study, the physical
      (mass and number concentration, and size distribution) and chemical (PAHs)
      properties were investigated at a major bus interchange in Singapore, influenced
      only by diesel exhausts. Number concentration and size distribution of particles
      were determined in real time, while the mass concentrations of PM2.5, and PAHs
      were measured during operating and nonoperating hours. The average mass
      concentrations of PM2.5 and PAHs increased by a factor of 2.34 and 5.18,
      respectively, during operating hours. The average number concentration was also
      elevated by a factor of 5.07 during operating hours. This increase in the
      concentration of PM2.5 particles and their chemical constituents during operating
      hours was attributable to diesel emissions from in-use buses based on the
      particle size analysis, correlation among PAHs, and the commonly used PAHs
      diagnostic ratios. To evaluate the potential health threat due inhalation of air
      pollutants released from diesel engines, the incremental lifetime cancer risk was
      also calculated for a maximally exposed individual. The findings indicate that
      the air quality at the bus interchange poses adverse health effects.

PMID- 16982531
TI  - Levels of persistent organic pollutant residues in human adipose and muscle
      tissues in Singapore.
AB  - Persistent organic pollutants (POPs), due to their persistence and
      bioconcentration in lipid-rich tissue, bioaccumulate in food chains, resulting in
      elevated concentrations in humans. This study was performed to determine and
      compare levels of POPs in human adipose and muscle tissues in the female
      population of Singapore. In total, 36 human adipose tissues and 8 human muscle
      tissues were collected from volunteer expectant mothers admitted to the National
      University Hospital Singapore for cesarean section delivery between August 2003
      and January 2005. Samples were analyzed using a validated and quality-assured gas
      chromatography-mass spectroscopy (GC-MS) method in conjunction with microwave
      assisted extraction (MAE). Analytes recoveries from certified reference
      materials, that is, IRMM-446 (polychlorinated biphenyls [PCBs] in pork fat) and
      BCR-430 (organochlorine pesticides in pork fat), were between 70 and 130%,
      indicating reliable analytical precision for this methodology. MAE efficiency for
      polybrominated diphenyl ethers (PBDEs) was compared to Soxhlet extraction (SE)
      efficiency and yielded comparable results (variation < 13%). Analytical results
      indicate that p,p'-DDE of the dichlorodiphenyltrichloroethane (DDT) residues
      group is the predominant compound in adipose tissue, followed by beta
      hexachlorocyclohexane (beta-HCH) among HCH isomers, then hexachlorobenzene (HCB)
      compound and specific PCB and PBDE congeners. Among the 36 adipose tissues, the
      lipid contents in adipose tissue were in the range of 60% to 95%, while in the 8
      muscle tissues, lipids were undetectable. However, the profile of PCBs and
      pesticide residues present in muscle tissues were similar to those in adipose
      tissues.

PMID- 16982532
TI  - Familial characteristics of kidney-yang deficiency and cold syndrome.
AB  - Family investigation is a reliable model to study the effects of both genetic and
      environmental factors on human health. This article studies kidney-yang
      deficiency syndrome and cold syndrome through family investigation and cDNA
      microarray technology, exploring the effects of both genetic and environmental
      factors on the health of family members. Particularly, these two syndromes were
      first assessed by the accumulated clinical scores measured by 40-item scoring
      tables among 15 family members. The family patterns were obtained and the
      correlation of these two syndromes was determined. Then the gene differential
      expression profiles among 12 family members were obtained using an 18,816 clones
      cDNA microarray. The profiles of the patients with typical kidney-yang deficiency
      syndrome and cold syndrome were compared to those of normal members and 89
      differential expression genes were found. Further, only 22 genes were identified
      as known functions, and most (16 genes) were associated with the regulation of
      metabolism, temperature feeling, and growth. Therefore, the formation and
      development of these two syndromes have not only genetic but also environmental
      factors, including living conditions and lifestyle.

PMID- 16982533
TI  - Detection of sildenafil analogues in herbal products for erectile dysfunction.
AB  - Sildenafil, the active ingredient in Viagra (Pfizer), is a prescription medicine
      used for erectile dysfunction. Compounds with chemical structures similar to that
      of sildenafil were isolated and purified during the analysis of some herbal
      products marketed for treatment of erectile dysfunction. Structural elucidation
      using liquid chromatography-diode array detection, infrared spectroscopy, liquid
      chromatography-tandem mass spectrometry, and nuclear magnetic resonance
      spectroscopy confirmed that the compounds were homosildenafil,
      hydroxyhomosildenafil, and acetildenafil. The implications of adulteration by
      compounds structurally related to prescription drugs are discussed. Unlike
      established drugs, the efficacy and safety of such analogues are largely unknown.
      This poses a great challenge for safety and health administrators to detect these
      modified structures and to regulate them. Consumers who use such adulterated
      products are at risk of developing serious adverse reactions, potentially leading
      to death. Greater collaboration and exchange of information between various
      health authorities, health professionals, academics, researchers, and industry,
      as well as public education, are key steps in the efforts to stem the growing
      trend of adulteration of herbal products by analogues of prescription drugs.

PMID- 16982534
TI  - A preliminary ecotoxicity study of pharmaceuticals in the marine environment.
AB  - Environmental fates and effects of pharmaceuticals in the aquatic environment
      have been the focus of recent research in environmental ecotoxicology. Worldwide
      studies of common over-the-counter pharmaceuticals have reported detectable
      levels in the aquatic environment, but there are few studies examining impacts on
      marine habitats. These drugs can affect the functions of various vertebrates and
      invertebrates. The stability of two pharmaceuticals, cyclizine (CYC) and
      prochlorperazine (PCZ), in seawater was examined under light and dark conditions,
      as well as the toxicity of these compounds to larvae of the barnacle Balanus
      amphitrite, which is a cosmopolitan marine organism found in most of the world's
      oceans. CYC was very stable under all the tested conditions. On the other hand,
      PCZ degraded in light but not in the dark, and was more stable in seawater than
      fresh water. For the barnacle larvae, the LC50 of prochlorperazine was 0.93
      microg/ml and the LC50 for CYC was approximately 0.04 microg/ml.

PMID- 16982535
TI  - Use of genetically modified viruses and genetically engineered virus-vector
      vaccines: environmental effects.
AB  - Despite major therapeutic advances, infectious diseases remain highly
      problematic. Recent advancements in technology in producing DNA-based vaccines,
      together with the growing knowledge of the immune system, have provided new
      insights into the identification of the epitopes needed to target the development
      of highly targeted vaccines. Genetically modified (GM) viruses and genetically
      engineered virus-vector vaccines possess significant unpredictability and a
      number of inherent harmful potential hazards. For all these vaccines, safety
      assessment concerning unintended and unwanted side effects with regard to
      targeted vaccinees has always been the main focus. Important questions concerning
      effects on nontargeted individuals within the same species or other species
      remain unknown. Horizontal transfer of genes, though lacking supportive
      experimental or epidemiological investigations, is well established. New hybrid
      virus progenies resulting from genetic recombination between genetically
      engineered vaccine viruses and their naturally occurring relatives may possess
      totally unpredictable characteristics with regard to host preferences and disease
      causing potentials. Furthermore, when genetically modified or engineered virus
      particles break down in the environment, their nuclei acids are released.
      Appropriate risk management is the key to minimizing any potential risks to
      humans and environment resulting from the use of these GM vaccines. There is
      inadequate knowledge to define either the probability of unintended events or the
      consequences of genetic modifications. The objective of this article is to
      highlight the limitations in environmental risk assessment and raise awareness of
      the potential risks involving the use of genetically modified viruses and
      genetically engineered virus-vector vaccines.

PMID- 16982536
TI  - Vitamin D2 from irradiated mushrooms significantly increases femur bone mineral
      density in rats.
AB  - A method has been optimized for the conversion of ergosterol in mushrooms to
      vitamin D2, and the vitamin D-enriched mushrooms have been tested for
      bioavailability of vitamin D2 using a rat model. Femur bone mineral density (BMD)
      of the experimental group of animals fed with vitamin D2 (1 microg/d) obtained
      from irradiated mushrooms was significantly increased. Femur BMD of two groups
      was significantly higher. Femur BMD of the experimental group was significantly
      elevated compared to initial femur BMD of the study group. Data indicate that
      vitamin D2 from ultraviolet (UV)-irradiated mushrooms was well absorbed and
      metabolized in animals.

PMID- 16982537
TI  - Persistent organic pollutants and adverse health effects in humans.
AB  - Persistent organic pollutants (POPs) are synthetic chemicals that have an
      intrinsic resistance to natural degradation processes, and are therefore
      environmentally persistent. The introduction of POPs into the environment from
      anthropogenic activities resulted in their widespread dispersal and accumulation
      in soils and water bodies, as well as in human and ecological food chains, where
      they are known to induce toxic effects. Due to their ubiquity in the environment
      and lipophilic properties, there is mounting concern over the potential risks of
      human exposure to POPs. This has led to the establishment of monitoring programs
      worldwide to determine prevailing levels of POPs in the population and to
      investigate the adverse health risks associated with background exposure. This
      article reviews the state of knowledge regarding residual levels of POPs in human
      adipose tissue worldwide, and highlights research data for POPs in the
      environment and human maternal adipose tissue in Singapore. Although
      concentrations are comparable to those observed elsewhere, longer term monitoring
      of a larger cross section of the population is warranted in order to establish
      temporal trends and potential risks to human health.

PMID- 16982538
TI  - The emerging evidence for Stereotactic Body Radiotherapy.

PMID- 16982539
TI  - Design of multi-institutional and cooperative group studies of SBRT.

PMID- 16982540
TI  - Accreditation and quality assurance for Radiation Therapy Oncology Group:
      Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung
      cancer.
AB  - Starting in 2002, the Radiation Therapy Oncology Group in North America began the
      process of developing multicenter prospective trials in lung cancer using
      Stereotactic Body Radiation Therapy (SBRT). Much of the work was based on the
      prospective single institution trials from Indiana University that had been
      presented and published. In late 2004, RTOG 0236 using SBRT for medically
      inoperable patients with clinical stage I non-small cell lung cancer (NSCLC) was
      activated for accrual. Prior to activation, representatives from the Lung, Image
      Guided Therapy, Physics, and Radiobiology Committees met on regular occasions to
      design the multicenter study and quality assurance measures. SBRT is not a black
      box, and the essence of the therapy had to be distilled via guidelines. Issues
      related to patient selection, method of dosimetry construction, equipment
      requirements, motion assessments and control, site accreditation, data exchange,
      and follow-up policies were worked out by compromise and consensus. RTOG 0236 has
      nearly completed its accrual. The Lung Committee has initiated the development of
      several other trials, each building on the last, to investigate the therapy in
      central tumors, in combinations with systemic therapy, in operable patients, and
      in lung metastases patients. The guidelines developed for RTOG 0236 will be
      refined to take advantage of more modern innovations including heterogeneity
      corrections and intensity modulation when appropriate. The development of RTOG
      0618 using SBRT in operable patients with early stage NSCLC is a testament to
      both the enthusiasm from already published works and prospective multicenter
      clinical testing using SBRT techniques.

PMID- 16982541
TI  - Factors important for efficacy of stereotactic body radiotherapy of medically
      inoperable stage I lung cancer. A retrospective analysis of patients treated in
      the Nordic countries.
AB  - We reviewed results of SBRT treatment of 138 patients with medically inoperable
      stage I NSCLC treated during 1996-2003 at five different centres in Sweden and
      Denmark. Mean age was 74 years (range 56-90) with 69 men and 72 women. SBRT was
      delivered using a 3D conformal multifield technique and a stereotactic body
      frame. Doses delivered were 30-48 Gy (65% isodose at the periphery of planning
      target volume, PTV) in 2-4 fractions. Equivalent dose in 2 Gy fractions (EQD2)
      was in the range of 50-100 Gy. Mean gross tumour volume (GTV) was 39 cm3 (2-436),
      and planning target volume was 101 cm3 (11-719). Overall response rate (CR, PR)
      was 61% (84/138). SD was noted in 36% (50/138). During a median follow-up period
      of 33 months (1-107), 16 (12%) local failures occurred, ten of which also
      included distant metastases. Local failure was associated with tumour size,
      target definition and central or pleura proximity. Distant metastases occurred in
      25% (35/138) of the patients. Ninety-one (65%) patients died during follow-up of
      which 55 patients (60%) died of other causes than lung cancer. Three- and 5-year
      overall survival was 52 and 26% respectively. Lung cancer specific 3- and 5-year
      overall survival was 66 and 40% respectively. Fifty nine percent (83/138) of the
      patients had no side effects. Fourteen patients experienced grade 3-4 toxicity
      according to radiation therapy oncology group (RTOG). EQD2 (> v.s.<55.6 Gy)
      showed a statistically significant benefit survival for the higher doses. SBRT
      for stage I NSCLC results in favourable local control not inferior to
      fractionated RT and with acceptable toxicity.

PMID- 16982542
TI  - Stereotactic hypofractionated radiotherapy in stage I (T1-2 N0 M0) non-small-cell
      lung cancer (NSCLC).
AB  - Stereotactic Radiotherapy has the potential to produce high local control rates
      with low risk of severe lung toxicity. From December 2000 to January 2006, 68
      inoperable patients (median age 76 years) with stage I NSCLC received definitive
      hSRT. A mean total dose of 37.5 Gy (24-40 Gy; 60%-isodose) in 3-5 fractions was
      applied. Immobilisation was carried out by means of a vacuum couch and low
      pressure foil (Medical Intelligence, Schwab Munchen, Germany). Staging procedures
      were thoracic and abdominal CT-scan, FDG-PET and CT or MRI of the brain in all
      patients. Clinical target volume was the tumor as seen in lung windowing of CT
      and in FDG-PET. Organ movements (6-22 mm) and patient positioning in the couch (3
      12 mm) were added as safety margin for the definition of the planning target
      volume (PTV), that was enclosed by the 60%-isodose. We observed four (6%) local
      tumor recurrences, resulting in an actuarial local tumor control rate of 96%, 88%
      and 88% after 1, 2 and 3 year follow-up. Nineteen patients died, with eight
      patients due to cancer (12%), two to local tumor progression alone. Cancer
      specific survival is 96%, 82% and 73% at 1, 2 and 3 years. Eleven patients died
      from comorbidities, making a 53% overall 3-year survival. Fifty five percent of
      the patients were affected by mild acute and subacute side effects, with only 3%
      experiencing pneumonitis III degrees . Late effects were pneumonitis III degrees
      in 1%, rib fractures in 3%, and benign pleural effusion in 2 patients.
      Hypofractionated SRT is safe even in elderly patients with stage I NSCLC and
      significantly reduced lung capacity. It leads to high local control rates and
      should be offered to patients not amenable for curative resection.

PMID- 16982543
TI  - Stereotactic body radiation therapy for centrally located lung lesions.
AB  - Presentation of outcomes of patients treated by stereotactic body radiation
      therapy (SBRT) for lung lesions located within or touching a 2 cm zone around
      major airways. Serial tomotherapeutic SBRT has been planned and delivered at our
      institution since August 2001. Of 108 patients treated for primary and secondary
      lung tumors, nine harbored tumors (8 metastases, 1 recurrent NSCLC) located in
      close proximity to carina, right and left main bronchi, right and left upper lobe
      bronchi, intermedius, right middle lobe, lingular, or right and left lower lobe
      bronchi. SBRT was delivered to total doses of 36 Gy in 3 fractions (n = 8) or 6
      fractions (n = 1), using a serial tomotherapy system (Nomos Peacock). We assessed
      local tumor control, clinical toxicity, normal tissue imaging changes, and
      overall survival. Median tumor volume was 26 cm3 (range 1.7 to 135 cm3). Tumor
      locations were hilar (n = 3), and parenchymal in six cases. Hilar lesions
      accounted for the three largest tumor volumes in the series. During a median
      follow-up of 10.6 months (range 2.5 to 41.5 months), all lesions treated were
      locally controlled as confirmed by CT or CT/PET imaging. Parenchymal imaging
      changes included focal lung fibrosis and major airway wall thickening. One
      occurrence of major airway occlusion (right lower lobe bronchus) was observed.
      This event was diagnosed by chest x-ray at 36 months, following treatment of the
      second largest hilar lesion in the present series. Based on the outcomes observed
      in this small sample series, SBRT for centrally located lung lesions appears
      feasible, was associated with low incidence of toxicities, and provided sustained
      local tumor control. However, long-term survival may be associated with major
      airway injury. As long-term follow-up in larger numbers of patients is lacking at
      this time, exclusion of patients with centrally located lesions may be considered
      when patients are treated in curative intent.

PMID- 16982544
TI  - Stereotactic Body Radiation Therapy (SBRT) for lung metastases.
AB  - The curative treatment of oligometastases with radiotherapy remains an area of
      active investigation. We hypothesise that treating oligometastases with SBRT can
      prolong life and potentially cure patients, while in patients with multiple lung
      metastases SBRT can improve quality of life. Fifty patients with lung metastases
      were treated on this study. Individuals with five or fewer total lesions were
      treated with curative intent. Individuals with > five metastases were treated
      palliatively. Most patients (62%) received 5 Gy/fraction for a total of 50 Gy.
      The number of targets treated per patient ranged from one to five (mean 2.6).
      Tumor sizes ranged from 0.3-7.7 cm in maximal diameter (median 2.1 cm). Mean
      follow-up was 18.7 months. Local control of treated lesions was obtained in 42 of
      49 evaluable patients (83%). Of the 125 total lesions treated, eight progressed
      after treatment (94% crude local control). The median overall survival time from
      time of treatment completion of the curatively treated patients was 23.4 months.
      The progression-free survival of the same group of patients was 25% and 16% at 12
      and 24 months, respectively. Grade 1 toxicity occurred in 35% of all the
      patients, 6.1% had grade 2 toxicity, and 2% had grade 3 toxicity. Excellent local
      tumor control rates with low toxicity are seen with SBRT. Median survival time
      and progression-free survival both appear better than that achieved with standard
      care alone. Long-term progression-free survival can be seen in a subset of
      patients when all tumors are targeted.

PMID- 16982545
TI  - Aggravation of dyspnea in stage I non-small cell lung cancer patients following
      stereotactic body radiotherapy: Is there a dose-volume dependency?
AB  - In SBRT for NSCLC, highly potent radiation doses are delivered to patients with
      frequent pre-irradiatory compromise of pulmonary function. For the risk of
      pulmonary toxicity to be minimized during SBRT planning, data on its dose-volume
      dependency is needed. In the present study, we analyse the association of dose
      volume histogram parameters with changes in dyspnea. The study concerns 28
      medically inoperable stage I NSCLC patients that received SBRT at our department
      between 2000 and 2003. A central dose of 45 Gy/3 fractions was delivered in 5-8
      days. WHO toxicity scoring of dyspnea was prospectively performed at baseline and
      during a 6-month follow-up post-SBRT. DVH parameters for pulmonary tissue were
      retrieved from the 3-D dose distributions. Aggravated dyspnea was registered in
      11 patients (40%). We found no association between DVH parameters and changes in
      dyspnea. Nor did we find any consistent temporal variations of dyspnea after
      SBRT. We identified COPD as the factor showing the closest association with
      aggravation of dyspnea. The observed aggravation of dyspnea following SBRT
      reflects habitual exacerbations of COPD rather than treatment-related toxicity.
      Concern about pulmonary toxicity should not be prohibitive for future studies
      targeting limitations to dose and volume.

PMID- 16982546
TI  - Phase II study on stereotactic body radiotherapy of colorectal metastases.
AB  - Surgical resection provides long term survival in approximately 30% of patients
      with colorectal carcinoma (CRC) liver metastases. However, only a limited number
      of patients with CRC-metastases are amendable for surgery. We have tested the
      effect of stereotactic body radiotherapy (SBRT) in the treatment of inoperable
      patients with CRC-metastases. Sixty-four patients with a total number of 141 CRC
      metastases in the liver (n = 44), lung (n = 12), lymph nodes (n = 3), suprarenal
      gland (n = 1) or two organs (n = 4) were treated with SBRT with a central dose of
      15 Gy x 3 within 5-8 days. Median follow-up was 4.3 years. After 2 years,
      actuarial local control was 86% and 63% in tumor and patient based analysis,
      respectively. Nineteen percent were without local or distant progression after 2
      years and overall survival was 67, 38, 22, 13, and 13% after 1, 2, 3, 4 and 5
      years, respectively. One patient died due to hepatic failure, one patient was
      operated for a colonic perforation and two patients were conservatively treated
      for duodenal ulcerations. Beside these, only moderate toxicities such as nausea,
      diarrhoea and skin reactions were observed. SBRT in patients with inoperable CRC
      metastases resulted in high probability of local control and promising survival
      rate. One toxic death and few severe reactions were observed. For the majority of
      patients, the treatment related toxicity was moderate.

PMID- 16982547
TI  - Stereotactic body radiation therapy for primary and metastatic liver tumors: A
      single institution phase i-ii study.
AB  - The feasibility, toxicity and tumor response of stereotactic body radiation
      therapy (SBRT) for treatment of primary and metastastic liver tumors was
      investigated. From October 2002 until June 2006, 25 patients not suitable for
      other local treatments were entered in the study. In total 45 lesions were
      treated, 34 metastases and 11 hepatocellular carcinoma (HCC). Median follow-up
      was 12.9 months (range 0.5-31). Median lesion size was 3.2 cm (range 0.5-7.2) and
      median volume 22.2 cm3 (range 1.1-322). Patients with metastases, HCC without
      cirrhosis, and HCC < 4 cm with cirrhosis were mostly treated with 3 x 12.5 Gy.
      Patients with HCC > or =4 cm and cirrhosis received 5 x 5 Gy or 3 x 10 Gy. The
      prescription isodose was 65%. Acute toxicity was scored following the Common
      Toxicity Criteria and late toxicity with the SOMA/LENT classification. Local
      failures were observed in two HCC and two metastases. Local control rates at 1
      and 2 years for the whole group were 94% and 82%. Acute toxicity grade > or =3
      was seen in four patients; one HCC patient with Child B developed a liver failure
      together with an infection and died (grade 5), two metastases patients presented
      elevation of gamma glutamyl transferase (grade 3) and another asthenia (grade 3).
      Late toxicity was observed in one metastases patient who developed a portal
      hypertension syndrome with melena (grade 3). SBRT was feasible, with acceptable
      toxicity and encouraging local control. Optimal dose-fractionation schemes for
      HCC with cirrhosis have to be found. Extreme caution should be used for patients
      with Child B because of a high toxicity risk.

PMID- 16982548
TI  - Stereotactic radiotherapy of primary liver cancer and hepatic metastases.
AB  - The purpose was to evaluate the clinical results of stereotactic radiotherapy in
      primary liver tumors and hepatic metastases. Five patients with primary liver
      cancer and 39 patients with 51 hepatic metastases were treated by stereotactic
      radiotherapy since 1997. Twenty-eight targets were treated in a "low-dose"-group
      with 3 x 10 Gy (n = 27) or 4 x 7 Gy (n = 1) prescribed to the PTV-encl. 65%
      isodose. In a "high-dose"-group patients were treated with 3 x 12 - 12.5 Gy (n =
      19; same dose prescription) or 1 x 26 Gy/PTV-enclosing 80%-isodose (n = 9).
      Median follow-up was 15 months (2-48 months) for primary liver cancer and 15
      months (2-85 months) for hepatic metastases. While all primary liver cancers were
      controlled, nine local failures (3-19 months) of 51 metastases were observed
      resulting in an actuarial local control rate of 92% after 12 months and 66% after
      24 months and later. A borderline significant correlation between dose and local
      control was observed (p = 0.077): the actuarial local control rate after 12 and
      24 months was 86% and 58% in the low-dose-group versus 100% and 82% in the high
      dose-group. In multivariate analysis high versus low-dose was the only
      significant factor predicting local control (p = 0.0089). Overall survival after
      1 and 2 years was 72% and 32% for all patients and was impaired due to systemic
      progression of disease. No severe acute or late toxicity exceeding RTOG/EORTC
      score 2 were observed. Stereotactic irradiation of primary liver cancer and
      hepatic metastases offers a locally effective treatment without significant
      complications in patients, who are not amenable for surgery. Patient selection is
      important, because those with low risk for systemic progression are more likely
      to benefit from this approach.

PMID- 16982549
TI  - Interim analysis of a prospective phase I/II trial of SBRT for liver metastases.
AB  - Stereotactic Body Radiation Therapy (SBRT) is a potent means of systemic
      cytoreductive therapy for selected patients with metastatic cancer. We here
      report an interim analysis of a prospective Phase I/II study of SBRT for liver
      metastases. Eligible patients with liver metastases met these criteria: (1)
      maximum tumor diameter < 6 cm; (2) < or =3 discrete lesions; (3) treatment
      planning confirmed > or = 700 cm3 of normal liver receives < or =15 Gy. The gross
      tumor volume (GTV) was expanded 5-10 mm to yield the planning target volume,
      which received 60 Gy in 3 fractions of SBRT over 3-14 days in the Phase II
      component of the trial. As of July, 2006, 36 patients have been enrolled: 18 in
      Phase I, 18 in Phase II. The median age was 58 years (range 27-91); the M:F ratio
      was 20:16. The most common primary sites were lung (n = 10), colorectal (n = 9),
      and breast (n = 4). Among 21 pts with > or = 6 months post-SBRT follow-up (median
      19 months, range 6-29), one instance of SBRT-related grade 3 toxicity occurred in
      subcutaneous tissue superficial to the liver. No grade IV toxicity occurred. For
      28 discrete lesions treated (median GTV 14 cm3, range 1-98) the 18 month
      actuarial local control estimate is 93%. This interim analysis indicates that a
      very high rate of durable in-field tumor control can be safely achieved with SBRT
      to 1-3 liver lesions as administered in this protocol, to a prescription dose of
      60 Gy in 3 fractions.

PMID- 16982550
TI  - Individualized image guided iso-NTCP based liver cancer SBRT.
AB  - A highly individualized stereotactic body radiotherapy (SBRT) strategy was
      developed to allow a wide spectrum of patients with liver cancer to be treated.
      This phase I/II study encompasses individualization of immobilization, radiation
      planning, PTV margin determination, image guidance strategy and prescription
      dose. Active breathing control breath hold is used to immobilize the liver when
      feasible. Image guidance strategies include orthogonal MV images and orthogonal
      kV fluoroscopy using the diaphragm for a surrogate for the liver, and kV cone
      beam CT using the liver or tumour for guidance. The prescription dose is
      individualized to maintain the same estimated risk of radiation-induced liver
      disease (RILD), based on a normal tissue complication probability (NTCP) model,
      with a maximum permitted dose of 60 Gy in 6 fractions. Since August 2003, 79
      patients with hepatocellular carcinoma (33), intrahepatic cholangiocarcinoma (12)
      and liver metastases (34) were treated. The median tumour volume was 293 cm3 (2.9
      3 088 cm3). The median prescribed dose was 36.6 Gy (24.0 Gy-57.0 Gy) in 6
      fractions. The median effective liver volume irradiated was 45% (9-80%). Sixty
      percent of patients were treated with breath hold to immobilize their liver.
      Intra-fraction reproducibility (sigma) of the liver with repeat breath holds was
      excellent (1.5 mm); however inter-fraction reproducibility (sigma) was worse (3.4
      mm). Image guidance reduced the residual systematic and random setup errors
      significantly.

PMID- 16982551
TI  - Absence of tissue reaction after focal high-dose irradiation of rabbit liver.
AB  - BACKGROUND: A focal reaction of the liver is radiologically seen after
      stereotactic high dose radiotherapy of liver tumors. The histological counterpart
      of this reaction should be clarified using an animal model. MATERIALS AND
      METHODS: Six New Zealand white rabbits were positioned on a special stereotactic
      set-up. Parts of the liver (1.5-8 ml) were irradiated with either 20-24 Gy/80% (n
      = 3) or 36 Gy/80% (n = 3). The animals were followed by CT examination up to 2
      years after radiotherapy. Finally, the animals were sacrificed and the liver
      macroscopically and microscopically inspected. RESULTS: No focal reaction could
      be observed in any liver at any time by CT examination. The liver macroscopically
      and microscopically showed no changes 6 months or 2 years after radiotherapy.
      CONCLUSION: Up to a single dose of 36 Gy/80%, rabbits seem to show no focal
      tissue reaction after high dose radiation therapy of small parts of the liver.

PMID- 16982552
TI  - A prospective Phase II trial of using extracranial stereotactic radiotherapy in
      primary and metastatic renal cell carcinoma.
AB  - A retrospective study has indicated that stereotactic radiotherapy (SRT) has a
      value in treating both primary tumors and singular metastatic lesions that cause
      local symptoms. Here we present the results of a prospective study evaluating the
      safety and local efficacy of SRT in metastatic or inoperable primary renal
      cancer. Thirty patients with metastatic renal cell carcinoma (RCC) or inoperable
      primary RCC received high-dose fraction SRT. In total, 82 lesions were treated.
      Dose/fractionation schedules varied depending on target location and size. The
      most frequently used fractionations were 8 Gy x 4, 10 Gy x 4, 15 Gy x 2 or 15 Gy
      x 3 prescribed to the periphery of the PTV. Local control, defined as
      radiologically stable disease (SD) or partial/complete response (PR/CR) was
      obtained in 98% of treated lesions but 19% of lesions were in patients with a
      follow time of less than 6 months. CR was observed in 21% of the patients and 58%
      of the patients had a partial volume reduction or local stable disease after a
      median follow-up of 52 months (range 11-66) for patients alive and 18 months
      (range 4-57) for deceased patients. Local progression was seen in two lesions.
      Side effects were grade I-II in 90% of cases. The overall survival was 32 months.
      SRT for patients with primary and metastatic RCC resulted in high local control
      rate with generally low toxicity. The method can thus be considered a therapeutic
      option to surgery in patients with a limited number of metastases, as local
      treatment in RCC with an indolent presentation or as a method of reducing tumor
      burden prior to medical treatment.

PMID- 16982553
TI  - Radiation administered as a large single dose or in a fractionated schedule: Role
      of the tumour vasculature as a target for influencing response.
AB  - This study was designed to demonstrate a differential tumour response to
      radiation given as a large single dose or fractionated, and to investigate the
      postulated role of the tumour vasculature as a target for this difference. A C3H
      mammary carcinoma grown in the right rear foot of female CDF1 mice was used when
      at 200 mm3. Radiation (240 kV x-rays) was given locally to the tumour bearing
      foot either as 1 x 20 Gy or 10 x 2 Gy (2 fractions/day). Tumour response was
      assessed by calculating tumour growth time (TGT; time to grow to 3 times
      treatment volume). Vascular effects were monitored by performing dynamic contrast
      enhanced-magnetic resonance imaging using a 3-Tesla magnet and the contrast agent
      gadolinium (Gd)-DTPA. The endpoint was the initial area under the concentration
      curve (IAUC) following Gd-DTPA. The mean (+/-1 S.E.) TGT for control mice was 4.0
      days (+/-0.2). This was significantly (Student's t-test; p < 0.05) increased to
      12.9 (+/-0.6) and 19.8 (+/-0.7) days, by 10 x 2 and 1 x 20 Gy, respectively. The
      mean (+/-1 S.E.) of the median IAUC values for control tumours was 8.4 mMs (+/
      0.5). This was non-significantly increased to 9.4 mMs (+/-0.4) 6-hours after 1 x
      20 Gy, but then significantly decreased to a nadir of 6.8 mMs (+/-0.5) after 48
      hours. IAUC recovered at longer time intervals. With 10 x 2 Gy, IAUC
      significantly decreased during irradiation, reaching 6.7 (+/-0.3) and 5.6 (+/
      0.3) mMs at the mid-point and end of the irradiation period, respectively. IAUC
      recovered 24-hours after irradiating before significantly decreasing to 4.4 mMs
      (+/-0.3) at 48-hours. Our results confirm that radiation given in a large single
      dose is superior to the same dose given in a more conventional fractionated
      schedule, but vascular-mediated effects did not account for this difference in
      radiation sensitivity.

PMID- 16982554
TI  - Image guided respiratory gated hypofractionated Stereotactic Body Radiation
      Therapy (H-SBRT) for liver and lung tumors: Initial experience.
AB  - To evaluate our initial experience with image guided respiratory gated H-SBRT for
      liver and lung tumors. The system combines a stereoscopic x-ray imaging system
      (ExacTrac X-Ray 6D) with a dedicated conformal stereotactic radiosurgery and
      radiotherapy linear accelerator (Novalis) and ExacTrac Adaptive Gating for
      dynamic adaptive treatment. Moving targets are located and tracked by x-ray
      imaging of implanted fiducial markers defined in the treatment planning computed
      tomography (CT). The marker position is compared with the position in
      verification stereoscopic x-ray images, using fully automated marker detection
      software. The required shift for a correct, gated set-up is calculated and
      automatically applied. We present our acceptance testing and initial experience
      in patients with liver and lung tumors. For treatment planning CT and
      Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) as well as magnetic
      resonance imaging (MRI) taken at free breathing and expiration breath hold with
      internal and external fiducials present were used. Patients were treated with 8
      11 consecutive fractions to a dose of 74.8-79.2 Gy. Phantom tests demonstrated
      targeting accuracy with a moving target to within +/-1 mm. Inter- and
      intrafractional patient set-up displacements, as corrected by the gated set-up
      and not detectable by a conventional set-up, were up to 30 mm. Verification
      imaging to determine target location during treatment showed an average marker
      position deviation from the expected position of up to 4 mm on real patients.
      This initial evaluation shows the accuracy of the system and feasibility of image
      guided real-time respiratory gated H-SBRT for liver and lung tumors.

PMID- 16982555
TI  - Feasibility report of image guided stereotactic body radiotherapy (IG-SBRT) with
      tomotherapy for early stage medically inoperable lung cancer using extreme
      hypofractionation.
AB  - We report on the technical feasibility, dosimetric aspects, and daily image
      guidance capability with megavoltage CT (MVCT) of stereotactic body radiotherapy
      (SBRT) using helical tomotherapy for medically inoperable T1/2 N0 M0 non-small
      cell lung cancer. Nine patients underwent treatment planning with 4D-CT in a
      double vacuum based immobilization system to minimize tumor motion and to define
      a lesion-specific 4D-motion envelope. Patients received 60 Gy in 5 fractions
      within 10 days to a PTV defined by a motion envelope plus a 6 mm expansion for
      microscopic extension and setup error using tomotherapy, with daily pretreatment
      MVCT image guidance. The primary endpoint was technical feasibility. Secondary
      endpoints were defining the acute and sub-acute toxicities and tumor response.
      Forty three of 45 fractions were successfully delivered, with an average delivery
      time of 22 minutes. MVCT provided excellent tumor visualization for daily image
      guidance. No significant tumor regression was observed on MVCT in any patient
      during therapy. Median mean normalized total doses were: tumor 117 Gy10; residual
      lung 9 Gy3. Maximum fraction-size equivalent dose values were: esophagus 5 Gy39;
      cord 7 Gy36. No patient experienced > or = grade 2 pulmonary toxicity. 3
      complete, 4 partial and 2 stable responses were observed, with <3 months median
      follow-up. The mean tumor regression is 72%. SBRT using tomotherapy proved to be
      feasible, safe and free of major technical limitations or acute toxicities. Daily
      pretreatment MVCT imaging allows for precise daily tumor targeting with the
      patient in the actual treatment position, and therefore provides for precise
      image guidance.

PMID- 16982556
TI  - Cone-beam CT based image-guidance for extracranial stereotactic radiotherapy of
      intrapulmonary tumors.
AB  - Cone-beam CT (CB-CT) based image-guidance was evaluated for extracranial
      stereotactic radiotherapy of intrapulmonary tumors. A total of 21 patients (25
      lesions: prim. NSCLC n = 6; pulmonary metastases n = 19) were treated with
      stereotactic radiotherapy (1 to 8 fractions). Prior to every fraction a CB-CT was
      acquired in treatment position, errors between planned and actual tumor position
      were measured and corrected. Intra- and inter-observer variability of manual
      evaluation of tumor position error was investigated and this manual method was
      compared with automatic image registration. Based on CB-CTs from 66 fractions the
      discrepancy (3-D vector) between planned and actual tumor position was 7.7 mm +/
      1.3 mm. Tumor position error relative to the bony anatomy was 5.3 mm +/-1.2 mm,
      the correlation between bony anatomy and tumor position was poor. Intra-observer
      and inter-observer variability of manual evaluation of tumor position error was
      0.9 mm +/-0.8 mm and 2.3 mm +/-1.1 mm, respectively. Automatic image registration
      showed highly reproducible results (<1 mm). However, compared with manual
      registration a systematic error was found in direction of predominant tumor
      breathing motion (2.5 mm vs 1.4 mm). Image-guidance using CB-CT was validated for
      high precision radiotherapy of intrapulmonary tumors. It was shown that both the
      planning reference and the verification image study have to consider tumor
      breathing motion.

PMID- 16982557
TI  - IGRT of prostate cancer; is the margin reduction gained from daily IG time
      dependent?
AB  - The aim of this study was to assess the set-up uncertainties and the possible CTV
      PTV margin reduction when adopting daily IGRT. Further, to identify any
      intrafraction time trends in the prostate movements to ensure the margin
      reduction gained from IGRT. Fifteen prostate cancer patients treated with IMRT
      using daily IG of three implanted fiducial markers were included. The
      interfraction uncertainties were assessed by statistically evaluating the daily
      prostate marker displacement. The intrafraction uncertainties were represented by
      the difference in prostate marker displacement before and after beam delivery. To
      evaluate any intrafraction time trends, the data points were divided into two
      groups with respect to time duration and statistically analysed. This study
      confirmed that daily IG considerably reduces the set-up uncertainties. Our
      results implied that if IGRT is performed on a daily basis, both systematic and
      random set-up errors will be reduced to a minimum, leading to a required set-up
      margin of only 1.5 mm. Results from measurements of intrafraction motions in time
      durations ranging from 2 to 27 min, indicated that a margin enlargement of 1 mm
      was required to account for the intrafraction uncertainties. The results did not
      suggest any significant time trends in the intrafraction uncertainties.

PMID- 16982558
TI  - Respiration correlated cone-beam computed tomography and 4DCT for evaluating
      target motion in Stereotactic Lung Radiation Therapy.
AB  - An image-guidance process for using cone-beam computed tomography (CBCT) for
      stereotactic body radiation therapy (SBRT) of peripheral lung lesions is
      presented. Respiration correlated CBCT on the treatment unit and four dimensional
      computed tomography (4DCT) from planning are evaluated for assessing respiration
      induced target motion during planning and treatment fractions. Image-guided SBRT
      was performed for 12 patients (13 lesions) with inoperable early stage non-small
      cell lung carcinoma. Kilovoltage (kV) projections were acquired over a 360 degree
      gantry rotation and sorted based on the pixel value of an image-based aperture
      located at the air-tissue interface of the diaphragm. The sorted projections were
      reconstructed to provide volumetric respiration correlated CBCT image datasets at
      different phases of the respiratory cycle. The 4D volumetric datasets were
      directly compared with 4DCT datasets acquired at the time of planning. For ten of
      12 patients treated, the lung tumour motion, as measured by respiration
      correlated CBCT on the treatment unit, was consistent with the tumour motion
      measured by 4DCT at the time of planning. However, in two patients, maximum
      discrepancies observed were 6 and 10 mm in the anterior-posterior and superior
      inferior directions, respectively. Respiration correlated CBCT acquired on the
      treatment unit allows target motion to be assessed for each treatment fraction,
      allows target localization based on different phases on the breathing cycle, and
      provides the facility for adaptive margin design in radiation therapy of lung
      malignancies. The current study has shown that the relative motion and position
      of the tumour at the time of treatment may not match that of the planning 4DCT
      scan. Therefore, application of breathing motion data acquired at simulation for
      tracking or gating radiation therapy may not be suitable for all patients - even
      those receiving short course treatment techniques such as SBRT.

PMID- 16982559
TI  - Three-dimensional spatial modelling of the correlation between abdominal motion
      and lung tumour motion with breathing.
AB  - The aim of this research was to investigate whether a spatial correlation could
      be found between an external 3-D respiratory signal and the tumour trajectory.
      The respiratory signal was obtained by tracking the abdominal movement and the
      tumour trajectory was obtained by automatically determining the tumour position
      in a series of portal images. Three different models, based on Systems
      Identification, are presented to model the correlation using a 1-D respiratory
      signal, a 3-D respiratory signal and a 3-D respiratory signal together with
      previously determined tumour positions. Adequate correlation was found for all
      models in the direction of the tumour movement with standard deviations of 0.89
      mm, 0.72 mm and 0.75 mm, respectively, and model fit of Rt2 = 0.19, 0.63 and
      0.82, respectively. Increasing the frame rate for the acquisition of portal
      images from 3 to 15 frames per second improved the standard deviation and model
      fit. In summary, it is possible to spatially correlate a 3-D respiratory signal
      with the tumour trajectory using this approach. The models presented provide a
      framework that can be extended to include more information if required. A 3-D
      respiratory signal is preferable to a 1-D signal in modelling the tumour motion
      that is not along the main axis of tumour movement.

PMID- 16982560
TI  - Comparison of respiratory surrogates for gated lung radiotherapy without internal
      fiducials.
AB  - An investigation was carried out to compare the ability of two respiratory
      surrogates to mimic actual lung tumor motion during audio coaching. The
      investigation employed video clips acquired after patients had had fiducial
      markers implanted in lung tumors to be used for image-guided stereoscopic
      radiotherapy. The positions of the markers in the clips were measured within the
      video frames and used as the standard for tumor volume motion. An external marker
      was tracked optically during the fluoroscopic acquisitions. An image correlation
      technique was developed to compute a gating signal from the fluoroscopic images.
      The correlation gating trace was similar to the optical gating trace in the phase
      regions of the respiratory cycle used for gating. A cross correlation analysis
      and comparison of the external optical marker gating with internal fluoroscopic
      gating was performed. The fluoroscopic image correlation surrogate was found to
      be superior to the external optical surrogate in the AP-views in four out of six
      cases. In one of the remaining two cases, the two surrogates performed
      comparably, while in the last case, the external fiducial trace performed best.
      It was concluded that fluoroscopic gating based on correlation of native image
      features in the fluoroscopic images will be adequate for respiratory gating.

PMID- 16982561
TI  - Use of motion tracking in stereotactic body radiotherapy: Evaluation of
      uncertainty in off-target dose distribution and optimization strategies.
AB  - Spatial accuracy in extracranial radiosurgery is affected by organ motion. Motion
      tracking systems may be able to avoid PTV enlargement while preserving treatment
      times, however special attention is needed when fiducial markers are used to
      identify the target can move with respect to organs at risk (OARs). Ten patients
      treated by means of the Synchrony system were taken into account. Sparing of
      irradiated volume and of complication probability were estimated by calculating
      treatment plans with a motion tracking system (Cyberknife Synchrony, Sunnyvale,
      CA, USA) and a PTV-enlargement strategy for ten patients. Six patients were also
      evaluated for possible inaccuracy of estimation of dose to OARs due to relative
      movement between PTV and OAR during respiration. Dose volume histograms (DVH) and
      Equivalent Uniform Dose (EUD) were calculated for the organs at risk. In the
      cases for which the target moved closer to the OAR (three cases of six), a small
      but significant increase was detected in the DVH and EUD of the OAR. In three
      other cases no significant variation was detected. Mean reduction in PTV volume
      was 38% for liver cases, 44% for lung cases and 8.5% for pancreas cases. NTCP for
      liver reduced from 23.1 to 14.5% on average, for lung it reduced from 2.5 to 0.1%
      on average. Significant uncertainty may arise from the use of a motion-tracking
      device in determination of dose to organs at risk due to the relative motion
      between PTV and OAR. However, it is possible to limit this uncertainty. The
      breathing phase in which the OAR is closer to the PTV should be selected for
      planning. A full understanding of the dose distribution would only be possible by
      means of a complete 4D-CT representation.

PMID- 16982562
TI  - Internal movement, set-up accuracy and margins for stereotactic body radiotherapy
      using a stereotactic body frame.
AB  - The aim of this study was to evaluate the uncertainty of patient immobilization
      within the Elekta body frame (SBF) used for stereotactic body radiotherapy (SBRT)
      and to suggest margins sufficient to ensure dose coverage to the gross target
      volume (GTV). The study was based on the evaluation of repeated CT-scans of 30
      patients treated by SBRT. The overall uncertainty was divided between uncertainty
      related to internal movement of the tumor and uncertainty in the patient set-up.
      Standard deviations of the overall tumor displacement were 2 mm, 3 mm and 4 mm in
      medial-lateral (m-l), anterior-posterior (a-p), and cranio-caudal (c-c)
      directions, respectively. In a model based on the data, an ellipsoid planned
      target volume (PTV) corresponding to the standard deviations in the orthogonal
      directions and a scaling factor, K defined a 3-dimentional (3-D) probability
      density. According to the model, a 90% probability of full dose coverage of the
      GTV was secured using margins of 9 mm (m-l), 9 mm (a-p) and 13 mm (c-c),
      respectively. The overall uncertainty was dominated by internal tumor movements
      whereas the set-up uncertainty of the patient in the SBF was less pronounced. It
      was concluded that the Elekta SBF is useful for immobilisation of patients for
      SBRT. However, due to internal movement conventional margins of 5 mm in m-l and a
      p and 10 mm in the c-c directions may be insufficient for full dose coverage.

PMID- 16982563
TI  - Tomotherapeutic stereotactic body radiation therapy: Techniques and comparison
      between modalities.
AB  - Presentation and comparison of tomotherapeutic intensity-modulated techniques for
      planning and delivery of stereotactic body radiation therapy. Serial
      tomotherapeutic SBRT has been planned and delivered at our institution since
      8/2001. Since 12/2005, 12 patients have been treated using a helical tomotherapy
      unit. For these 12 patients both helical and serial tomotherapy plans were
      computed and clinically approved. Techniques and considerations of tomotherapy
      SBRT planning, associated image-guidance, and delivery are presented. The
      respective treatment plans were compared based on dosimetric parameters as well
      as time to develop a treatment plan and delivery times. Also the associated
      quality of megavoltage CT (MVCT) image-guidance inherent to the helical
      tomotherapy unit was assessed. Tumor volumes averaged 9.3, 9.8, and 58.7 cm3 for
      liver, lung, and spinal targets. Helical and serial tomotherapy plans showed
      comparable plan quality with respect to maximum and average doses to the gross
      tumor and planning target volumes. Time to develop helical tomotherapy plans
      averaged 3.5 h while serial tomotherapy planning consistently required less than
      one hour. Treatment delivery was also slower using helical tomotherapy, with
      differences of less than 10 min between modalities. MVCT image-guidance proved
      satisfactory for bony and lung targets, but failed to depict liver lesions, owing
      to poor soft-tissue contrast. SBRT planning and delivery is clinically feasible
      using either tomotherapeutic modality. While treatment planning time was
      consistently shorter and more readily accomplished in a standardized approach
      using the serial tomotherapy modality, actual plan quality and treatment delivery
      times are grossly comparable between the modalities. MVCT volumetric image
      guidance, was observed to be valuable for thoracic and spinal target volumes,
      whereas it proved challenging for liver targets.

PMID- 16982564
TI  - Lung tumor tracking during stereotactic radiotherapy treatment with the
      CyberKnife: Marker placement and early results.
AB  - Lung tumor tracking during stereotactic radiotherapy with the CyberKnife requires
      the insertion of markers in or close to the tumor. To reduce the risk of
      pneumothorax, three methods of marker placement were used: 1) intravascular coil
      placement, 2) percutaneous intrathoracal, and 3) percutaneous extrathoracal
      placement. We investigated the toxicity of marker placement and the tumor
      response of the lung tumor tracking treatment. Markers were placed in 20 patients
      with 22 tumors: 13 patients received a curative treatment, seven a palliative.
      The median Charlson Comorbidity Score was 4 (range: 1-8). Platinum fiducials and
      intravascular embolisation coils were used as markers. In total, 78 markers were
      placed: 34 intrathoracal, 23 intravascular and 21 extrathoracal. The PTV equaled
      the GTV + 5 mm. A median dose of 45 Gy (range: 30-60 Gy, in 3 fractions) was
      prescribed to the 70-85% isodose. The response was evaluated with a CTscan
      performed 6-8 weeks after the last treatment and routinely thereafter. The median
      follow-up was 4 months (range: 2-11). No severe toxicity due to the marker
      placement was seen. Pneumothorax was not seen. The local control was 100%. Four
      tumors in four patients showed a complete response, 15 tumors in 14 patients a
      partial response, and three tumors in two patients with metastatic disease had
      stable disease. No severe toxicity of marker placement was seen due to the
      appropriate choice of one of the three methods. CyberKnife tumor tracking with
      markers is feasible and resulted in excellent tumor response. Longer follow-up is
      needed to validate the local control.

PMID- 16982565
TI  - 4D imaging for target definition in stereotactic radiotherapy for lung cancer.
AB  - Stereotactic radiotherapy of Stage I lung tumors has been reported to result in
      high local control rates that are far superior to those obtained with
      conventional radiotherapy techniques, and which approach those achieved with
      primary surgery. Breathing-induced motion of tumor and target tissues is an
      important issue in this technique and careful attention should be paid to the
      contouring and the generation of individualized margins. We describe our
      experience with the use of 4DCT scanning for this group of patients, the use of
      post-processing tools and the potential benefits of respiratory gating.

PMID- 16982566
TI  - Dummy run for a phase II study of stereotactic body radiotherapy of T1-T2 N0M0
      medical inoperable non-small cell lung cancer.
AB  - In forthcoming multicentre studies on stereotactic body radiotherapy (SBRT)
      compliance with volume and dose prescriptions will be mandatory to avoid
      unnecessary heterogeneity bias. To evaluate compliance in a multicentre setting
      we used two cases from an ongoing phase II study of SBRT of T1-T2N0M0 inoperable
      NSCLC in a dummy run oriented on volumes and doses. Six Scandinavian centres
      participated. Each centre received CT-scans covering the whole lung volumes of
      two patients with instructions to follow the study protocol when outlining tumour
      and target volumes, prescribing doses and creating dose plans. Volumes and doses
      of the 12 dose plans were evaluated according to the study protocol. For the two
      patients the GTV volume range was 24 to 39 cm3 and 26 to 41 cm3, respectively.
      The PTV volume range was 90 to 116 cm3, and 112 to 155 cm3, respectively. For all
      plans the margin between CTV and PTV in all directions followed in detail the
      protocol. The prescribed dose was for all centres 45 Gy/3 fractions (isocentre
      dose about 66 Gy). The mean GTV doses ranged from 63 to 67 Gy and from 63 to 68
      Gy, respectively. The minimum doses for GTV were between 50-64 Gy and between 55
      65 Gy, respectively. The dose distribution was conformed to PTV for 10 of 12
      plans and 2 of 12 plans from one centre had sub-optimal dose distribution. Most
      of the volume and dose parameters for the participating centres showed fully
      acceptable compliance with the study protocol.

PMID- 16982567
TI  - Dose distributions in SBRT of lung tumors: Comparison between two different
      treatment planning algorithms and Monte-Carlo simulation including breathing
      motions.
AB  - In stereotactic body radiotherapy (SBRT) of lung tumors, dosimetric problems
      arise from: 1) the limited accuracy in the dose calculation algorithms in
      treatment planning systems, and 2) the motions with the respiration of the tumor
      during treatment. Longitudinal dose distributions have been calculated with Monte
      Carlo simulation (MC), a pencil beam algorithm (PB) and a collapsed cone
      algorithm (CC) for two spherical lung tumors (2 cm and 5 cm diameter) in lung
      tissue, in a phantom situation. Respiratory motions were included by a
      convolution method, which was validated. In the static situation, the PB
      significantly overestimates the dose, relative to MC, while the CC gives a
      relatively accurate estimate. Four different respiratory motion patterns were
      included in the dose calculation with the MC. A "narrowing" of the longitudinal
      dose profile of up to 20 mm (at about 90% dose level) is seen relative the static
      dose profile calculated with the PB.

PMID- 16982568
TI  - Monte Carlo characterization of target doses in stereotactic body radiation
      therapy (SBRT).
AB  - To compare finite-size pencil beam/equivalent path-length (FSPB/EPL) and Monte
      Carlo (MC) SBRT dose computations for serial tomotherapy and to quantitatively
      assess dose differences between the dose calculation methods. Based on 72 SBRT
      plans for pulmonary targets, FSPB/EPL, considering the inhomogeneous lung
      environment, and MC calculations were performed to establish differences between
      FSPB/EPL predicted dose and MC derived doses. Compared with MC, FSPB/EPL
      consistently overestimated minimum doses to the clinical target volume and
      planning target volumes by an average of 18.1+/-7.15% (range 4 to 33.4%), and
      21.9+/-10.4% (range 1.2 to 45.5%), respectively. The respective mean target dose
      differences were 15.5+/-7.4% (2.8-36.4%) and 19.2+/-7.6% (3.6-40.1%). Deviations
      from MC doses were lesion size and location dependent, with smaller lesions
      completely embedded into lung parenchyma being most susceptible. Larger lesion in
      contact with mediastinum and chest wall showed lesser differences. In comparison
      with MC dose calculation, FSPB/EPL overestimates doses delivered to pulmonary
      SBRT targets. The observed dose differences may have impact on local tumor
      control rates, and may deserve consideration when using fast, but less accurate
      dose calculation methods.

PMID- 16982569
TI  - Change in subjective age among older people over an eight-year follow-up:
      'getting older and feeling younger?'.
AB  - The purpose of this prospective study was to describe changes in subjective age
      over an 8-year period among community-dwelling people aged 65 to 84 years in
      Finland. At the baseline 1155 respondents met study criteria and 451 of these
      participated in the follow-up study. Participants described in years the age they
      felt themselves to be (feel age) and their preferred age (ideal age). Discrepancy
      scores relative to chronological age were calculated for feel age and ideal age.
      No significant mean-level changes were observed in the age discrepancy scores
      over the 8-year time frame. The baseline discrepancy between chronological and
      feel age remained constant among 48% of the participants, with 26% reporting a
      younger and 26% an older feel age. Similar patterns were observed in the
      discrepancy between chronological age and ideal age. The findings point both to
      stability and to individual variability in feel and preferred age identification
      over time in older adults.

PMID- 16982570
TI  - Validation study of the three-objects-three-places test: a screening test for
      Alzheimer's disease.
AB  - The aim of the present study was to validate a short, ecological test of episodic
      memory for the screening of Alzheimer's disease (AD). The validation was
      performed by computing intrarater reliability, homogeneity, internal coherence,
      convergent, discriminant and known group validities in the performance of normal
      subjects (N = 65), mild cognitive impairment (MCI) patients (N = 114), and AD (N
      = 44) and non-AD demented (N = 39) patients. Intrarater reliability was 0.88,
      homogeneity ranged from 0.81 to 0.97, and internal coherence was 0.87. With
      respect to convergent and discriminant validities, the test loaded strongly on
      memory factor (value = 0.64) and weakly on other nonmemory factors. The known
      group validity showed a specificity between 87% and 91% and a sensitivity between
      92% and 100% in correctly identifying AD in age classes ranging from 50 to 65 and
      66 to 80 years. The test is a valid instrument for the screening of AD.

PMID- 16982572
TI  - Physical activity moderates time-of-day differences in older adults' working
      memory performance.
AB  - Based on a synthesis of the literature on time of day and physical fitness
      effects on cognition, the current study examined whether physical activity
      moderated time-of-day differences in older adults' performance on a working
      memory task. Sedentary older adults' working memory performance declined
      significantly from morning to evening, whereas more active older adults performed
      similarly across the day. This interaction did not extend to performance on a
      simple reaction time task. A novel explanation based on the selective effect of
      mental fatigue on executive control processes is proposed.

PMID- 16982571
TI  - A common cognitive profile in elderly fallers and in patients with Parkinson's
      disease: the prominence of impaired executive function and attention.
AB  - The present study examined the cognitive profile of elderly fallers relative to
      healthy elderly controls and patients with Parkinson's disease (PD), a positive
      control group, using a computerized battery. Fallers performed more poorly than
      controls on executive function, attention, and motor skills, but performed
      comparably on memory, information processing and the Mini-Mental State
      Examination. A similar profile was evident for PD patients. However, unlike PD
      patients, fallers were abnormally inconsistent in their reaction times. These
      findings indicate that elderly fallers may have a unique cognitive processing
      deficit (i.e., variability of response timing) and underscore the importance of
      executive function and attention as potential targets for fall risk screening and
      interventions.

PMID- 16982574
TI  - The human skin as a hormone target and an endocrine gland.
AB  - Hormones influence the development and function of human skin which also produces
      and releases hormones. Recently attention has been focused on identifying and
      understanding the complex endocrine properties of human skin, such as expression
      and function of specific hormone receptors, synthesis of hormones from major
      classes of compounds used by the body for general purposes, organized metabolism,
      activation, inactivation and elimination of the hormones in specialized cells of
      the tissue, exertion of biological activity and release of tissue hormones in the
      circulation. Specifically, hormones exert their biological effects on the skin
      through interaction with high-affinity receptors, such as several receptors for
      peptide hormones and neurotransmitters, steroid and thyroid hormones. Hormones
      exhibit a wide range of biological activities on the skin with distinct effects
      caused by growth hormone/insulin-like growth factor-I, neuropeptides, sex
      steroids, glucocorticoids, retinoids, vitamin D, peroxisome proliferator
      activated receptor ligands, eicosanoids, melatonin and serotonin. Human skin
      produces, activates or inactivates metabolically numerous hormones which are
      probably important for skin functions but also for functions of the entire human
      organism, such as sex hormones, especially in aged individuals, insulin-like
      growth factor and -binding proteins, neuropeptides, prolactin, catecholamines,
      retinoids, steroids, vitamin D and eicosanoids. These functions are undertaken in
      most cases by different skin cell populations in a coordinated way, indicating
      the endocrine autonomy of the skin. Characteristic examples are the metabolic
      pathways of the corticotropin-releasing hormone/propiomelanocortin axis,
      steroidogenesis, vitamin D and retinoids. The human skin is, thus, the largest,
      peripheral endocrine organ.

PMID- 16982573
TI  - Internally generated memory testing: results of repeated test administration.
AB  - A critical memory skill rarely clinically tested is the ability to remember self
      generated material. Healthy aged participants (n = 30; Experiment 1) and pilot
      participants with probable Alzheimer disease (pAD) (n = 9; Experiment 2) were
      twice administered a memory test including both internally generated and
      externally supplied items for recall. Healthy aged participants were biased to
      recall internally originating over externally supplied material on first, but not
      second, presentation. However, pAD participants demonstrated internal bias during
      both sessions. The pAD participants were also specifically impaired when told to
      remember internal material. This study provides further evidence that internally
      originating items can be used to assess memory. In pAD, memory for internal
      material with specific attempt to remember may be selectively impaired.

PMID- 16982575
TI  - Pegvisomant: a new treatment modality for acromegaly.
AB  - Acromegaly, a multisystemic disease resulting from excessive growth hormone (GH)
      and insulin-like growth factor-I (IGF-I) levels in adults, is associated with a
      two-to-threefold increase in mortality. The available treatment options (surgery,
      radiotherapy and medical treatment with somatostatin analogues or dopamine
      agonists) fail to achieve the currently accepted goals of therapy in a
      substantial number of patients. Pegvisomant, a newly developed GH receptor
      antagonist, represents a novel treatment modality for this disease. It binds with
      the GH receptor and induces internalization, but blocks receptor signaling
      events, thereby reducing IGF-I production. The two main published studies suggest
      that it is the most potent medical therapy with greater specificity, without
      being dependent on the tumour characteristics. However, apart from its high cost
      and the dilemmas raised concerning the appropriateness of using serum IGF-I
      concentrations as a marker of disease activity, it may also occasionally be
      associated with elevations in liver enzyme levels. Further studies are required
      to confirm its high success rates as well as to investigate the possibility of
      inducing an increase in the pituitary tumour size. Currently, pegvisomant is a
      second line treatment for acromegaly with an adjuvant role and possibly of
      greater value in cases of resistance to other therapeutic options.

PMID- 16982576
TI  - Hormones in sports: growth hormone abuse.

PMID- 16982577
TI  - Increased leptin levels in preeclampsia: associations with BMI, estrogen and SHBG
      levels.
AB  - Leptin is secreted mainly by the white adipose tissue but is also synthesized in
      several non-adipose tissue organs including the placenta. Serum leptin levels are
      increased in normal pregnancies and are higher in preeclamptic than normal
      pregnant women. There is, however, a lack of empirical evidence of an independent
      association of serum leptin levels and preeclamsia. We have studied cross
      sectionally 18 3rd trimester preeclamptic women, 28 3rd trimester and 30 2nd
      trimester control women to confirm the reported increase of serum leptin in
      preeclampsia and to assess whether elevated leptin levels in preeclampsia
      increase the variance explained by body mass index (BMI), androgens, estrogens
      and/or sex hormone binding globulin (SHBG). Anthropometric, demographic and
      hormonal data were analyzed using linear and logistic regression models. RESULTS:
      Leptin is significantly increased in preeclampsia by univariate analysis, but use
      of multivariate analysis indicates that the elevated leptin levels are not
      associated with preeclampsia independently from BMI, estrogens and SHBG.
      CONCLUSION: This study confirms that leptin levels are higher in women with
      preeclampsia than in controls and demonstrates that serum leptin levels do not
      add to the prediction of preeclampsia after accounting for BMI, estrogen and SHBG
      levels of preeclamptic women.

PMID- 16982578
TI  - Clinical aspects of hyperthyroidism in hospitalised patients in Albania.
AB  - The purpose of this study was to evaluate certain clinical aspects of
      hyperthyroidism in Albania, which is an iodine deficient country, as it is known
      that iodine intake may influence the type of thyroid hyperfunction. The files of
      sixty-six patients with thyrotoxicosis who were hospitalised for their disease
      were retrospectively analysed. 59.1% of these patients suffered from toxic
      multinodular goiter, 27.3% from Grave's disease (toxic diffuse goiter), 10.6%
      from toxic adenoma, 1.5% from iodide-induced hyperthyroidism and 1.5% from
      transient hyperthyroidism due to subacute thyroiditis. There was an increased
      female to male ratio (83.3% vs 16.7%, respectively, p<0.001). 83.9% of all
      hyperthyroid patients lived in cities, while 16.1% lived in villages.
      Ophthalmopathy was found in 11.1% of patients with Graves' disease, and
      thyrotoxic heart disease was found in 14% of patients with thyrotoxicosis. 71.9%
      of all patients with hyperthyroidism were treated with propylthiouracil (PTU),
      while 28.1% of them were treated with methimazole; 67.2% of all these patients
      also received propranolol hydrochloride, while 32.8% were prescribed atenolol.
      Compliance was lower than that reported in other studies as only 41% of all
      patients received their treatment regularly. Side effects from treatment with
      antithyroid drugs were as follows: 4.1% (2/48) of patients treated with
      propylthiouracil presented leukopenia with agranulocytosis, and 6.1% of them
      toxic hepatitis, while 11.1% (2/18) of patients treated with methimazole
      presented agranulocytosis. In conclusion, the mode of presentation and side
      effects of hyperthyroidism appears to be different in Albania when compared with
      other countries, probably as a result of iodine deficiency and/or possibly
      nutritional status. Compliance with treatment is lower than that reported in
      other series, while antithyroid drug side effects seem to be more frequent. The
      latter observation may be due to the fact that only hospitalised patients were
      analysed in this study.

PMID- 16982579
TI  - Langerhans' cell histiocytosis in an adult patient manifested as recurrent skull
      lesions and Diabetes Insipidus.
AB  - We describe a 57-year old female with the diagnosis of skull and meningeal
      Langerhans' cell histiocytosis who was treated with the combination of
      azathioprine and methotrexate. Although the skull lesions improved considerably
      on this regimen, the patient developed diabetes insipidus while the anterior
      pituitary function remained intact.

PMID- 16982580
TI  - Treatment of recurrent gastrointestinal haemorrhage in a patient with von
      Willebrand's disease with administration of octreotide LAR and propranolol.
AB  - We report a patient with von Willebrand' s disease who had had recurrent and life
      threatening bleeding from the gastrointestinal tract. Despite extensive
      investigation, no apparent cause of haemorrhage was identified. He was
      successfully treated with combined administration of octreotide LAR (long-acting
      release) and propranolol. This is the first report on the successful use of
      octreotide LAR in a patient with von Willebrand' s disease.

PMID- 16982581
TI  - Primary adrenal lymphoma presented with adrenal insufficiency.
AB  - We report a 71-year old man who presented with symptoms of adrenal insufficiency
      and large bilateral adrenal masses. Computed tomography guided FNA biopsy was not
      diagnostic. However, because of the rapid growth of the masses, the negative
      workup for primary malignancy and the strong clinical suspicion of a lymphoma, an
      open biopsy was performed and a B-cell lymphoma was disclosed.

PMID- 16982582
TI  - Recent developments in transsphenoidal surgery of pituitary tumors.

PMID- 16982584
TI  - Histopathology of thyroid tumors. An overview.

PMID- 16982583
TI  - Management of diabetic retinopathy. An overview.

PMID- 16982585
TI  - Factors associated with body mass index in adults from Northern Greece.
AB  - The aim of this large scale epidemiological cross-sectional study was to
      investigate potential factors, such as age, gender, socioeconomic status
      (measured as educational level and profession), smoking habits and physical
      activity, that could influence Body Mass Index (BMI) in a large sample of Greeks
      of Central Macedonia. Overall, 4032 adults (1296 males and 2736 females), age:
      44.3+/-14.5 y (mean +/- SD) participated in this study. Candidates were contacted
      by phone and provided self-reported data about their age, weight, height,
      socioeconomic status, smoking habits and physical activity. Our results showed
      that the mean BMI value was 26.2+/-5 (x+/-SD). Factors associated with BMI were
      age (positively), physical activity and education level (negatively) in both
      genders and smoking habits (negatively) only in women. Obesity prevalence was
      higher in females, and in middle age, in civil employees, less educated and non
      smoking subjects of both genders while overweight prevalence was higher in males,
      and in old age, in less educated and non-smoking subjects of both genders. In
      conclusion, several environmental factors were found to be associated with
      obesity or overweight indices in our sample of Greek individuals.

PMID- 16982586
TI  - The serum triiodothyronine to thyroxine (T3/T4) ratio in various thyroid
      disorders and after Levothyroxine replacement therapy.
AB  - In order to examine the significance of differences in the
      triiodothyronine/thyroxine (T3/T4) ratio in the achievement of euthyroidism and
      in different thyroidal diseases, we studied 1050 subjects: 233 were euthyroid
      (Eu), 239 hypothyroid (Hypo) with initial TSH levels >15 mU/L, 273 hypothyroid on
      substitution therapy with L-thyroxine alone and TSH values of 0.35-3.5 mU/L,
      (hypoRx), 236 hyperthyroid (hyper) and 69 in the acute phase of subacute
      thyroiditis De Quervain's (DQ). The ratio of T3/T4 was calculated using the
      conventional values. RESULTS: The values of T3/T4 ratio in the various categories
      were: Eu= 15.89, Hypo= 24.12, hyper= 19.57, hypoRx= 13.42, DQ= 15.16. The T3/T4
      ratio was lower in the hypoRx group than in the EU group (P <0.001), although
      neither TSH values nor T3 values showed any differences between these two groups,
      whereas T4 levels were significantly higher in the hypoRx group (Eu= 7.99+/-1.46,
      hypoRx = 9.11+/-1.58, P< 0.001). The T3/T4 ratio in the DQ group was comparable
      to that of the Eu group, but significantly lower than the hyper group (P=0.95
      between Eu and DQ, P<0.001 between DQ and hyper). CONCLUSIONS: These findings
      indicate that in hypothyroid patients, L-T4-replacement that is sufficient to
      maintain a normal serum TSH is accompanied by a serum T4 that is higher than in
      normal individuals and may not result in an appropriately normal serum T3
      concentration. In Thyrotoxicosis, a ratio of total T3/T4 >18.9 suggests Graves'
      disease or toxic multinodular goiter whereas T3/T4 <16 suggests thyroiditis
      (subacute or silent).

PMID- 16982587
TI  - Familial paraganglioma: a novel presentation of a case and response to therapy
      with radiolabelled MIBG.
AB  - Phaeochromocytomas (PC) and paragangliomas are disorders of the sympatho
      adrenomedullary system. They are chromaffin-containing neuroendocrine tumors of
      neural crest origin that contain catecholamine-secreting granules: they arise
      from either the adrenal medulla (phaeochromocytomas) or from extra-adrenal neural
      crest derivatives e.g. the sympathetic chain (paragangliomas). The term
      paraganglioma is also used for vascular head and neck tumors derived from
      parasympathetic tissue, which commonly arise at the carotid bifurcation. It has
      been reported that some 10% of phaeochromocytomas are part of a familial
      syndrome, although recent data have suggested that germline mutations in known
      predisposing syndromes, such as multiple endocrine neoplasia type 2 (MEN2) and
      Von Hippel-Lindau (VHL), occur in a much higher percentage. However, familial
      genetic syndromes have been said to be less common in paragangliomas, although
      more recently described genetic syndromes may not have been considered. Thus,
      there is increasing evidence that mutations of subunits of the succinate
      dehydrogenase gene (SDHB, SDHC & SDHD) may confer susceptibility to
      paragangliomas and head-and-neck paragangliomas (HNPGL). We report a case of a
      patient with a previously published gene mutation in SDHB who had a single
      paraganglioma arising from the bladder with a characteristic clinical
      presentation, and in whom there was a positive family history of a HNPGL. He has
      demonstrated malignant recurrence with metastases which have been treated, so far
      successfully, with radiolabelled MIBG.

PMID- 16982588
TI  - Symptomatic pheochromocytoma with normal urinary catecholamine metabolites.
AB  - A 61-year old female presented with paroxysmal hypertension and a 4.5cm left
      adrenal mass on CT scan. Repeated measurements of 24-hour urinary fractionated
      metanephrines, total catecholamines and vanillylmandelic acid (VMA) were within
      normal range. A further scintigraphic study with (131)I -metaiodobenzylguanidine
      ((131)I-MIBG) revealed selective concentration of the radiotracer, corresponding
      to the CT mass. After adequate preoperative treatment, successful surgical
      excision of the tumor was performed and the pathological examination confirmed
      the diagnosis of a cystic pheochromocytoma with a 2cm solid tumor. On
      reevaluation three months later using (131)I-MIBG, no evidence of remaining or
      recurrent disease was found. The patient, off any antihypertensive medication,
      reported mild recurrent hypertension and panic attacks that were adequately
      controlled with antidepressants. This is a rare case of a symptomatic
      pheochromocytoma without elevated urine catecholamines and metanephrines.
      According to the literature, plasma free metanephrines would be the ideal test
      for biochemical detection of the tumor. However, in the event that they are not
      available and there is a high clinical suspicion for the presence of
      pheochromocytoma, as in our patient, we suggest performance of a functional
      nuclear medicine study, such as (131)I-MIBG, to confirm the clinical diagnosis.

PMID- 16982589
TI  - Unresolved issues, dilemmas and points of interest in thyroid cancer: a current
      perspective.
AB  - Thyroid cancer (TC) is the commonest endocrine malignancy. In the overwhelming
      majority of cases, thyroid carcinomas are well-differentiated malignancies that
      respond favorably to treatment; however, this outcome cannot be absolutely
      guaranteed. The absence of large prospective randomized clinical trials in TC-due
      to its low incidence and protracted clinical course in cases with
      persistent/recurrent metastatic disease-results in considerable debates regarding
      the optimal treatment and follow-up regimens in this malignancy. Some of these
      debates originated several decades ago, yet are still ongoing despite interim
      advancements in other domains of oncology. Here we discuss what we believe are
      the issues of major controversy in TC; these are mentioned in the following non
      exhaustive list: (i) the optimal management of solitary and multiple thyroid
      nodules; (ii) the role of basal calcitonin measurements in the diagnostic
      investigation of nodular thyroid disease; (iii) the extent of the initial
      operation after establishment of the diagnosis of TC; (iv) the intensity and
      frequency of radioactive iodine (RAI; (131)I) therapies (especially in patients
      with persistent/recurrent metastatic disease); (v) the degree and duration of
      long-term thyroid hormone suppression therapy (THST) required for optimal
      outcomes in TC patients; (vi) the optimal management of patients with RAI
      refractory disease or other "high-risk" clinicopathologic features; and, finally,
      (vii) the optimal algorithm for lifelong follow-up of TC patients after their
      initial treatment. We present elements of the above controversies as pertinent to
      the various types of TC. We have opted for breadth rather than depth of
      commentary, at the same time providing the reader with extended up-to-date
      bibliography.

PMID- 16982590
TI  - The role of estrogens in cardiovascular disease in the aftermath of clinical
      trials.
AB  - The effects of estrogens on reproductive tissues and climacteric symptoms are
      unambiguous. However, their effects on other tissues and, in particular, the
      cardiovascular system remain controversial. In general, premenopausal women are
      protected from coronary heart disease (CHD) compared with aged-matched men but
      this ;female protection' appears to be lost after menopause, suggesting
      beneficial effects of female sex hormones on the cardiovascular system. This view
      has been supported by observational studies showing that estrogen replacement
      therapy (ERT) is associated with a 30% to 50% decrease in CHD risk in
      postmenopausal women. Nevertheless, randomized clinical trials in postmenopausal
      women, with or without pre-existing CHD, have found no benefits to combined
      hormone replacement therapy (HRT). A possible explanation for these apparently
      contradictory findings may relate to the divergent effects of estrogens depending
      on the state of the vascular endothelium. It has been suggested that estrogens
      may prevent the development and early progression of atherosclerosis by
      contributing to the maintenance of endothelial health but may have a neutral or
      negative effect on a dysfunctional endothelium or on advanced atheromatous
      lesions. Furthermore, it is possible that estrogens have adverse effects on other
      cardiovascular risk factors such as thrombosis and inflammation. It is also
      conceivable that a decline in vascular estrogen receptor expression with
      advancing age, through methylation of the estrogen receptor promoter, prevents
      postmenopausal women from deriving the beneficial cardiovascular effects of
      estrogens. In conclusion, estrogens possibly prevent the development of
      atherosclerosis through favourable effects on an intact endothelium, but once the
      vascular endothelium is damaged, the prothrombotic and possibly proinflammatory
      effects of estrogens are likely to predominate and prove harmful.

PMID- 16982591
TI  - Glucocorticoids and bone: cellular, metabolic and endocrine effects.

PMID- 16982592
TI  - The effect of long-term somatostatin analogue treatment on free and total insulin
      like growth factor (IGF) -I, -II and IGF binding protein -1, -2 and -3 serum
      levels in euthyroid patients with active thyroid eye disease.
AB  - The aim of this study was to investigate the effect of long-term somatostatin
      analogue (SM-a) treatment on serum levels of free (F) and total (T) insulin-like
      growth factor (IGF)-I, -II and IGF binding protein (IGFBP) - 1, -2 and -3 in
      euthyroid patients with active thyroid ophthalmopathy. For this purpose, we
      measured the above-mentioned parameters in 21 patients (11M, 10F), aged 50.8+/
      11.8 years (range 35-70) and 19 healthy individuals matched for age, gender and
      body mass index (BMI). A total of 4 SM-a (sandostatin LAR((R))-30) injections,
      each monthly, were administered in each patient and measurements were performed
      prior to treatment and 20-30 days after the last injection, while in control
      individuals the same determinations were performed only once. All patients had
      active thyroid eye disease (TED), with clinical activity scores (CAS) >/= 4
      (5.3+/-1.1) and positive orbital octreoscan in both eyes. Serum F and T IGF-I and
      IGF-II were determined using non-competitive, time-resolved monoclonal
      immunofluorometric assays. IGFBP-1 and IGFBP-2 were determined by an in-house
      radioimmunoassay, while IGFBP-3 by commercially available IRMA. Our results
      showed that F and T IGF-I, -II and IGFBP-1, -2 and -3 levels in patients before
      and after administration of SM-a were comparable and the levels did not differ
      significantly from those of controls. Furthermore, no statistically significant
      differences emerged in the ratio between molar weights of TIGF-I/IGFBP-3 and TIGF
      II/IGFBP-3, as well as in the ratio of F/TIGF-I and F/TIGF-II in patients before
      and after SM-a therapy. Fourteen patients (66%) experienced a decline in CAS of
      at least >1 point in each eye after SM-a administration, whereas in the remaining
      the CAS did not change. Finally, no relationship was found between the levels of
      the above-mentioned parameters (post therapy) and CAS, octreoscan scores and
      thyroid hormones levels. In conclusion, we showed that although SM-a
      administration in euthyroid patients with active TED had a beneficial effect in a
      significant percentage of patients, this effect was not associated with a decline
      in the circulating IGF-I, -II and IGFBP-1, -2 and -3 levels, at least under the
      conditions of the present study. It can be postulated that if the mechanism of
      action of SM-a is through reduction of IGF-I levels, this effect is possibly
      exerted in the retrobulbar tissues by local paracrine/autocrine action.

PMID- 16982593
TI  - The concurrence of microalbuminuria and retinopathy with cardiovascular risk
      factors; reliable predictors of asymptomatic coronary artery disease in type 2
      diabetes.
AB  - People with diabetes mellitus type 2 (DM2) have a greater risk for premature
      morbidity and mortality due to cardiovascular disease than the general
      population: cardiovascular disease accounts for 75% of deaths in this population
      group. We examined whether or not the association of clinical cardiovascular risk
      factors (RF) with both microalbuminuria (MA) and diabetic retinopathy (DR)
      constitutes reliable evidence for the existence of asymptomatic coronary artery
      disease (CAD), as assessed by positive myocardial thallium scintiscan using the
      SPECT method (Tl-scan) in patients with DM2. The study included 76 individuals
      with DM2 (54 men and 22 women, aged 46-70 years), with a negative history for
      infarction and negative clinical or ECG findings of CAD. In all patients, 3
      overnight (11 pm - 7 am) urine collections were made for evaluation of MA.
      Fundoscopy after dilatation and a Tl-scan (reference method) were also carried
      out. In addition, blood pressure and waist/hip ratio were measured and smoking
      habits were recorded. In the 35 patients with a positive Tl-scan (46%) a higher
      (p<0.001) incidence of MA, DR, hypertension, smoking and higher waist/hip ratio
      were detected. Of the 16 patients with concurrent presence of MA and DR, 15 had a
      positive Tl-scan (94%), whereas the Tl-scan was negative in 30/36 (83%) patients
      with absence of both MA and DR. One or no cardiovascular RF in the absence of MA
      and DR increased the prediction of a negative Tl-scan to 100% (NPV: 1.00). Based
      only on history, fundoscopy and MA testing, and without resorting to expensive
      and laborious testing procedures, it is possible to safely distinguish patients
      with type 2 diabetes, who require no further investigations for asymptomatic CAD.

PMID- 16982594
TI  - Growth hormone deficiency associated with moyamoya disease in a 16 year-old boy.
AB  - Moyamoya disease is a rare cerebrovascular disorder which, according to a few
      literature reports, can coexist with hypothalamic-pituitary dysfunction. We
      report a 16 year-old boy referred to our Department because of short stature and
      headaches. He additionally, at admission, presented discrete facial dysmorphy,
      bruxism, luxation of temporomandibular joint and cryptorchidism. The height was
      146 cm (-4.3 SDS); the sexual development was P2G2A1 and the bone age 11.5 years.
      The intellectual development was normal. No focal neurological deficits were
      observed. Based on baseline and stimulated hormonal values, isolated growth
      hormone deficiency was diagnosed. Malformation of the cerebral vessel was
      suspected on magnetic resonance imaging and upon angiocomputed tomography and
      panangiography, a picture suggesting moyamoya disease was obtained. Growth
      hormone has been administered with daily injections at the dose of 0.025
      mg/kg/24h, and the first year height velocity was 12 cm/yr. No adverse events
      resulting from the treatment have been noted so far. This case indicates that GH
      deficiency may be associated with moyamoya disease, possibly resulting from
      chronic cerebrovascular insufficiency.

PMID- 16982595
TI  - A tribute to Carl Adolph von Basedow: to commemorate 150 years since his death.

PMID- 16982596
TI  - The pathophysiology of miscarriage in women with polycystic ovary syndrome.
      Review and proposed hypothesis of mechanisms involved.

PMID- 16982597
TI  - The adult consequences of feminising genital surgery in infancy. A growing
      skepticism.

PMID- 16982598
TI  - Growth, pubertal development, skeletal maturation and bone mass acquisition in
      athletes.
AB  - The genetic potentials for growth can be fully expressed only under favourable
      environmental conditions. Excessive physical training may negatively affect
      growth, especially during puberty. Sports that require a strict control of energy
      input in the presence of a high energy output are of particular concern. In
      gymnastics, a different pattern in skeletal maturation was observed, leading to
      an attenuation of growth potential ins Artistic Gymnasts (AG), more pronounced in
      males than in females, whereas in female Rhythmic Gymnasts (RG) the genetic
      predisposition to growth was preserved because of a late catch-up growth
      phenomenon. In all other sports not requiring strict dietary restrictions, no
      deterioration of growth has been documented. Intensive physical training and
      negative energy balance modify the hypothalamic pituitary set point at puberty,
      prolong the prepubertal stage and delay pubertal development and menarche in a
      variety of sports. In elite RG and AG the prepubertal stage is prolonged and
      pubertal development is entirely shifted to a later age, paralleling the bone age
      rather than the chronological age. Bone formation, and, consequently, BMD are
      enhanced by physical activity. In athletes, high-impact loading activities have
      been shown to improve BMD, while in sports requiring a lean somatotype, the delay
      in skeletal maturation and pubertal development, resulting from hypoestrogenemia,
      predisposes athletes to osteopenia. In AG, an increase in bone density is
      observed using the bone age as denominator.

PMID- 16982599
TI  - A Paradox: the roles of inositolphosphoglycans in mediating insulin sensitivity
      and hyperandrogenism in the polycystic ovary syndrome.

PMID- 16982600
TI  - Roles of protein kinase A (PKA) and PKC on corticotropin-releasing hormone (CRH)
      induced elevation of cytosolic calcium from extra-and intra-cellular sources.
AB  - Corticotropin-releasing hormone (CRH) affects cytosolic calcium ion levels. The
      aim of the present work was to examine the role of protein kinase A (PKA)- and
      PKC-dependent signalling pathways in mediating the effect of CRH on calcium ion
      influx (from extra-cellular sources) and calcium ion mobilization (from intra
      cellular stores). In this study, we employed a well-known model of neural crest
      derived cells, the PC12 rat pheochromocytoma cell line. We found that CRH
      increased the concentration of cytosolic calcium ions in calcium-rich and in
      calcium-free media. In both conditions, an inhibitor of PKA phosphorylation
      abolished the effect of CRH. In contrast, the inhibitor of PKC phosphorylation
      blocked the effect of CRH only in calcium-free conditions. The phorbol ester PMA,
      activator of PKC, accelerated the steep of the curve of cytosolic calcium ion
      increase from intra-cellular stores. These data suggest that: (a) CRH induces
      calcium ion entrance into the cytoplasm from both extra-cellular sources (influx)
      and from intra-cellular stores (mobilization); (b) the PKA-dependent signalling
      pathway mediates both effects of CRH; and (c) the PKC-dependent signalling
      pathway mediates only the CRH-induced mobilization of calcium ions from intra
      cellular stores. Thus, this is the first report demonstrating that distinct
      signalling pathways control the effects of CRH on calcium ion influx and on
      calcium ion mobilization from intra-cellular stores.

PMID- 16982601
TI  - Growth without growth hormone (GH): a case report.
AB  - Growth without growth hormone (GH) has occasionally been described in patients
      with organic pituitary pathology, and even more rarely in patients with
      idiopathic pituitary hormone deficiency. The mechanism of growth without GH
      remains a mystery. We describe a 17-year old male who grew 38.5 cm in height over
      a 7-year period, despite the fact that he had established panhypopituitarism. The
      hypopituitarism was initially attributed to a presumptive hypothalamic hamartoma
      which was not, however, confirmed on subsequent and prolonged follow-up. Regular
      endocrine evaluation confirmed persistent anterior and posterior pituitary
      hormonal deficiencies with severe concomitant hyperinsulinemia as shown by an
      exaggerated insulin response to a standard oral glucose tolerance test. In our
      patient, a postulated mechanism could be the severe hyperinsulinemia, acting
      either through the insulin and/or IGF receptors and thus potentiating the
      mitogenic effect. This case illustrates that final height attainment within or
      above target height may occur in patients with idiopathic pituitary hormonal
      deficiency despite persistent, severe GH insufficiency.

PMID- 16982602
TI  - The significance of the number seven in ancient Greece and its relation to
      Endocrinology.

PMID- 16982603
TI  - A short history of the thyroid gland.

PMID- 16982604
TI  - Identification of the heparin-binding determinants within fibronectin repeat
      III1: role in cell spreading and growth.
AB  - Fibronectins are high molecular mass glycoproteins that circulate as soluble
      molecules in the blood, and are also found in an insoluble, multimeric form in
      extracellular matrices throughout the body. Soluble fibronectins are polymerized
      into insoluble extracellular matrix (ECM) fibrils via a cell-dependent process.
      Recent studies indicate that the interaction of cells with the ECM form of
      fibronectin promotes actin organization and cell contractility, increases cell
      growth and migration, and enhances the tensile strength of artificial tissue
      constructs; ligation of integrins alone is insufficient to trigger these
      responses. Evidence suggests that the effect of ECM fibronectin on cell function
      is mediated in part by a matricryptic heparin-binding site within the first III1
      repeat (FNIII1). In this study, we localized the heparin-binding activity of
      FNIII1 to a cluster of basic amino acids, Arg613, Trp614, Arg615, and Lys617.
      Site-directed mutagenesis of a recombinant fibronectin construct engineered to
      mimic the ECM form of fibronectin demonstrates that these residues are also
      critical for stimulating cell spreading and increasing cell proliferation. Cell
      proliferation has been tightly correlated with cell area. Using integrin- and
      heparin-binding fibronectin mutants, we found a positive correlation between cell
      spreading and growth when cells were submaximally spread on ECM protein-coated
      surfaces at the time of treatment. However, cells maximally spread on vitronectin
      or fibronectin still responded to the fibronectin matrix mimetic with an increase
      in growth, indicating that an absolute change in cell area is not required for
      the increase in cell proliferation induced by the matricryptic site of FNIII1.

PMID- 16982605
TI  - Phosphorylation of specific serine residues in the PKR activation domain of PACT
      is essential for its ability to mediate apoptosis.
AB  - Activation of the latent protein kinase, PKR, by extracellular stresses and
      triggering of resultant cellular apoptosis are mediated by the protein, PACT,
      which itself gets phosphorylated in stressed cells. We have analyzed the
      underlying biochemical mechanism by carrying out alanine-scanning mutagenesis of
      the PKR activation domain of PACT. Among the indispensable residues identified
      were two serine residues, whose phosphorylation was essential for the cellular
      actions of PACT. Two-dimensional gel analysis, Western analysis using
      phosphoamino acid-specific antiserum, and in vivo 32P labeling of PACT
      demonstrated that constitutive phosphorylation of one of the two residues,
      Ser246, was required for stress-induced phosphorylation of the other, Ser287.
      Substitution of either of them by threonine or aspartic acid, but not alanine,
      was tolerated. Substitution of both residues with the phosphoserine mimetic,
      aspartic acid, produced a mutant PACT that, unlike the wild-type protein, caused
      PKR activation and apoptosis, even in unstressed cells. These results indicate
      that phosphorylation of specific serine residues in the activation domain of PACT
      is the major mode of transmission of cellular stress response to PKR.

PMID- 16982606
TI  - Interdomain interactions in the tumor suppressor discs large regulate binding to
      the synaptic protein GukHolder.
AB  - Multidomain scaffolding proteins are central components of many signaling
      pathways and are commonly found at membrane specializations. Here we have shown
      that multiple interdomain interactions in the scaffold Discs Large (Dlg) regulate
      binding to the synaptic protein GukHolder (GukH). GukH binds the Src homology 3
      (SH3) and guanylate kinase-like (GK) protein interaction domains of Dlg, whereas
      an intramolecular interaction between the two domains inhibits association with
      GukH. Regulation occurs through a PDZ domain adjacent to the SH3 that allows GukH
      to interact with the composite SH3-GK binding site, but PDZ ligands inhibit GukH
      binding such that Dlg forms mutually exclusive PDZ ligand and GukH cellular
      complexes. The PDZ-SH3-GK module is a common feature of membrane associate
      guanylate kinase scaffolds such as Dlg, and these results indicate that its
      supramodular architecture leads to regulation of Dlg complexes.

PMID- 16982607
TI  - FRAT1, a substrate-specific regulator of glycogen synthase kinase-3 activity, is
      a cellular substrate of protein kinase A.
AB  - FRAT1, like its Xenopus homolog glycogen synthase kinase-3 (GSK-3)-binding
      protein, is known to inhibit GSK-3-mediated phosphorylation of beta-catenin. It
      is currently unknown how FRAT-GSK-3-binding protein activity toward GSK-3 is
      regulated. FRAT1 has recently been shown to be a phosphoprotein in vivo; however,
      the responsible kinase(s) have not been determined. In this study, we identified
      Ser188 as a phosphorylated residue in FRAT1. The identity of the kinase that
      catalyzes Ser188 phosphorylation and the significance of this phosphorylation to
      FRAT1 function were investigated. Protein kinase A (PKA) was found to
      phosphorylate Ser188 in vitro as well as in intact cells. Importantly, activation
      of endogenous cAMP-coupled beta-adrenergic receptors with norepinephrine
      stimulated the phosphorylation of FRAT1 at Ser188. GSK-3 was also able to
      phosphorylate FRAT1 at Ser188 and other residues in vitro or when overexpressed
      in intact cells. In contrast, endogenous GSK-3 did not lead to significant FRAT1
      phosphorylation in cells, suggesting that GSK-3 is not a major FRAT1 kinase in
      vivo. Phosphorylation of Ser188 by PKA inhibited the ability of FRAT1 to activate
      beta-catenin-dependent transcription. In conclusion, PKA phosphorylates FRAT1 in
      vitro as well as in intact cells and may play a role in regulating the inhibitory
      activity of FRAT1 toward GSK-3.

PMID- 16982608
TI  - Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL
      10 and assembly of the signaling complex.
AB  - Interleukin-10 receptor 2 (IL-10R2) is a critical component of the IL-10.IL
      10R1.IL-10R2 complex which regulates IL-10-mediated immunomodulatory responses.
      The ternary IL-10 signaling complex is assembled in a sequential order with the
      IL-10.IL-10R1 interaction occurring first followed by engagement of the IL-10R2
      chain. In this study we map the IL-10R2 binding site on IL-10 using surface
      plasmon resonance and cell-based assays. Critical IL-10R2 binding residues are
      located in helix A adjacent to the previously identified IL-10R1 recognition
      surface. Interestingly, IL-10R2 binding residues located in the N-terminal end of
      helix A exhibit large structural differences between unbound cIL-10 and cIL-10.IL
      10R1 crystal structures. This suggests IL-10R1-induced conformational changes
      regulate IL-10R2 binding and assembly of the ternary IL-10.IL-10R1.IL-10R2
      complex. The basic mechanistic features of the assembly process are likely shared
      by six additional class-2 cytokines (viral IL-10s, IL-22, IL-26, IL-28A, IL28B,
      and IL-29) to promote IL-10R2 binding to six additional receptor complexes. These
      studies highlight the importance of structure in regulating low affinity protein
      protein interactions and IL-10 signal transduction.

PMID- 16982609
TI  - Antagonistic interactions of kleisins and DNA with bacterial Condensin MukB.
AB  - MukBEF is a bacterial SMC (structural maintenance of chromosome) complex required
      for faithful chromosome segregation in Escherichia coli. The SMC subunit of the
      complex, MukB, promotes DNA condensation in vitro and in vivo; however, all three
      subunits are required for the function of MukBEF. We report here that MukEF
      disrupts MukB x DNA complex. Preassembled MukBEF was inert in DNA binding or
      reshaping. Similarly, the association of MukEF with DNA-bound MukB served to
      displace MukB from DNA. When purified from cells, MukBEF existed as a mixture of
      MukEF-saturated and unsaturated complexes. The holoenzyme was unstable and could
      only bind DNA upon dissociation of MukEF. The DNA reshaping properties of
      unsaturated MukBEF were identical to those of MukB. Furthermore, the unsaturated
      MukBEF was stable and proficient in DNA binding. These results support the view
      that kleisins are not directly involved in DNA binding but rather bridge distant
      DNA-bound MukBs.

PMID- 16982610
TI  - The anaphase-promoting complex/cyclosome inhibitor Emi2 is essential for meiotic
      but not mitotic cell cycles.
AB  - Vertebrate oocytes awaiting fertilization are arrested at metaphase of meiosis II
      by cytostatic factor (CSF). This arrest is due to inhibition of the anaphase
      promoting complex/cyclosome, in part by a newly identified protein, Emi2 (xErp1).
      Emi2 is required for maintenance of CSF arrest in egg extracts, but its function
      in CSF establishment in oocytes and the normal embryonic cell cycle is unknown.
      Here we show that during oocyte maturation, Emi2 appears only after metaphase I,
      and its level peaks at CSF arrest (metaphase II). In M phase, Emi2 undergoes a
      phosphorylation-dependent electrophoretic shift. Microinjection of antisense
      oligonucleotides against Emi2 into stage VI oocytes blocks progression through
      meiosis II and the establishment of CSF arrest. Recombinant Emi2 rescues CSF
      arrest in these oocytes and also causes CSF arrest in egg extracts and in
      blastomeres of two-cell embryos. Fertilization triggers rapid, complete
      degradation of Emi2, but it is resynthesized in the first embryonic cell cycle to
      reach levels 5-fold lower than during CSF arrest. However, depletion of the
      protein from cycling egg extracts does not prevent mitotic cell cycle
      progression. Thus, Emi2 plays an essential role in meiotic but not mitotic cell
      cycles.

PMID- 16982611
TI  - Two xyloglucan xylosyltransferases catalyze the addition of multiple xylosyl
      residues to cellohexaose.
AB  - Xyloglucan (XyG) is the principal hemicellulose found in the primary cell walls
      of most plants. XyG is composed of a beta-(1,4)-glucan backbone that is
      substituted in a regular pattern with xylosyl residues, which are added by at
      least one and likely two or three xylosyltransferase (XT) enzymes. Previous work
      identified seven Arabidopsis thaliana candidate genes, one of which (AtXT1) was
      shown to encode a protein with XT activity (Faik, A., Price, N. J., Raikhel, N.
      V., and Keegstra, K. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 7797-7802). We
      expressed both AtXT1 and a second closely related gene, now called AtXT2, in
      insect cells and demonstrated that both have XT activity for cellopentaose and
      cellohexaose acceptor substrates. Moreover, we showed that cellohexaose was a
      significantly better acceptor substrate than cellopentaose. Product structural
      characterization showed that AtXT1 and AtXT2 preferentially added the first
      xylosyl residue to the fourth glucosyl residue from the reducing end of both
      acceptors. Furthermore, when the ratio of UDP-xylose to cellohexaose and the
      reaction time were increased, both AtXT1 and AtXT2 added a second xylosyl residue
      adjacent to the first, which generated dixylosylated cellohexaose. On the basis
      of these results, we concluded that AtXT1 and AtXT2 have the same acceptor
      specificities and generate the same products in vitro. The implications of these
      results for understanding in vivo XyG biosynthesis are considered.

PMID- 16982612
TI  - Mutational analysis of the Medicago glycosyltransferase UGT71G1 reveals residues
      that control regioselectivity for (iso)flavonoid glycosylation.
AB  - The plant glycosyltransferase UGT71G1 from the model legume barrel medic
      (Medicago truncatula) glycosylates flavonoids, isoflavonoids, and triterpenes. It
      can transfer glucose to each of the five hydroxyl groups of the flavonol
      quercetin, with the 3'-O-glucoside as the major product, and to the A-ring 7
      hydroxyl of the isoflavone genistein. The sugar donor and acceptor binding
      pockets are located in the N and C termini, respectively, of the recently
      determined crystal structure of UGT71G1. The residues forming the binding pockets
      of UGT71G1 were systematically altered by site-directed mutagenesis. Mutation of
      Phe148 to Val, or Tyr202 to Ala, drastically changed the regioselectivity for
      quercetin glycosylation from predominantly the 3'-O-position of the B-ring to the
      3-O-position of the C ring. The Y202A mutant exhibited comparable catalytic
      efficiency with quercetin to the wild-type enzyme, whereas efficiency was reduced
      3-4-fold in the F148V mutant. The Y202A mutant gained the ability to glycosylate
      the 5-hydroxyl of genistein. Additional mutations affected the relative
      specificities for the sugar donors UDP-galactose and UDP-glucuronic acid,
      although UDP-glucose was always preferred. The results are discussed in relation
      to the design of novel biocatalysts for production of therapeutic flavonoids.

PMID- 16982613
TI  - Spatial compartmentalization of tumor necrosis factor (TNF) receptor 1-dependent
      signaling pathways in human airway smooth muscle cells. Lipid rafts are essential
      for TNF-alpha-mediated activation of RhoA but dispensable for the activation of
      the NF-kappaB and MAPK pathways.
AB  - Tumor necrosis factor (TNF)-alpha-induced activation of RhoA, mediated by TNF
      receptor 1 (TNFR1), is a prerequisite step in a pathway that leads to increased
      20-kDa light chain of myosin (MLC20) phosphorylation and airway smooth muscle
      contraction. In this study, we have investigated the proximal events in TNF-alpha
      induced RhoA activation. TNFR1 is localized to both lipid raft and nonraft
      regions of the plasma membrane in primary human airway smooth muscle cells. TNF
      alpha engagement of TNFR1 recruited the adaptor proteins TRADD, TRAF-2, and RIP
      into lipid rafts and activated RhoA, NF-kappaB, and MAPK pathways. Depletion of
      cholesterol from rafts with methyl-beta-cyclodextrin caused a redistribution of
      TNFR1 to nonraft plasma membrane and prevented ligand-induced RhoA activation. By
      contrast, TNF-alpha-induced activation of NF-kappaB and MAPKs was unaffected by
      methyl-beta-cyclodextrin indicating that, in airway smooth muscle cells,
      activation of these pathways occurred independently of lipid rafts. Targeted
      knockdown of caveolin-1 completely abrogated TNF-alpha-induced RhoA activation,
      identifying this raft-resident protein as a positive regulator of the activation
      process. The signaling adaptors TRADD and RIP were also found to be necessary for
      ligand-induced RhoA activation. Taken together, our results suggest that in
      airway smooth muscle cells, spatial compartmentalization of TNFR1 provides a
      mechanism for generating distinct signaling outcomes in response to ligand
      engagement and define a mechanistic role for lipid rafts and caveolin-1 in TNF
      alpha-induced activation of RhoA.

PMID- 16982614
TI  - Apigenin inhibition of involucrin gene expression is associated with a specific
      reduction in phosphorylation of protein kinase Cdelta Tyr311.
AB  - Apigenin is a plant-derived flavanoid that has significant promise as a skin
      cancer chemopreventive agent. In the present study, we examine the mechanism
      whereby apigenin regulates normal human keratinocyte differentiation. Expression
      of involucrin (hINV), a marker of keratinocyte differentiation, is increased by
      differentiating agents via a protein kinase Cdelta (PKCdelta), Ras, MEKK1, MEK3
      cascade that increases AP1 factor level and AP1 factor binding to DNA elements in
      the hINV promoter. We show that apigenin inhibits this response. Apigenin
      suppresses the 12-O-tetradeconylphorbol-13-acetate-dependent increase in AP1
      factor expression and binding to the hINV promoter and the increase in hINV
      promoter activity. Apigenin also inhibits the increase in promoter activity
      observed following overexpression of PKCdelta, constitutively active Ras, or
      MEKK1. The suppression of PKCdelta activity is associated with reduced
      phosphorylation of PKCdelta-Y311. The physiological importance of this
      phosphorylation event was confirmed by showing that the PKCdelta phosphorylation
      defective mutant, PKCdelta-Y311F, is less able to increase hINV promoter
      activity. Activation of hINV promoter activity by the green tea polyphenol, (-)
      epigellocathecin-3-gallate, is also inhibited by apigenin, suggesting that the
      two chemopreventive agents can produce opposing actions in keratinocytes.
      Additional studies show that the apigenin-dependent suppression of
      differentiation is associated with reduced cell proliferation but that there is
      no evidence of apoptosis.

PMID- 16982615
TI  - Structure of FitAB from Neisseria gonorrhoeae bound to DNA reveals a tetramer of
      toxin-antitoxin heterodimers containing pin domains and ribbon-helix-helix
      motifs.
AB  - Neisseria gonorrhoeae is a sexually transmitted pathogen that initiates
      infections in humans by adhering to the mucosal epithelium of the urogenital
      tract. The bacterium then enters the apical region of the cell and traffics
      across the cell to exit into the subepithelial matrix. Mutations in the fast
      intracellular trafficking (fitAB) locus cause the bacteria to transit a polarized
      epithelial monolayer more quickly than the wild-type parent and to replicate
      within cells at an accelerated rate. Here, we describe the crystal structure of
      the toxin-antitoxin heterodimer, FitAB, bound to a high affinity 36-bp DNA
      fragment from the fitAB promoter. FitA, the antitoxin, binds DNA through its
      ribbon-helix-helix motif and is tethered to FitB, the toxin, to form a
      heterodimer by the insertion of a four turn alpha-helix into an extensive FitB
      hydrophobic pocket. FitB is composed of a PIN (PilT N terminus) domain, with a
      central, twisted, 5-stranded parallel beta-sheet that is open on one side and
      flanked by five alpha-helices. FitB in the context of the FitAB complex does not
      display nuclease activity against tested PIN substrates. The FitAB complex points
      to the mechanism by which antitoxins with RHH motifs can block the activity of
      toxins with PIN domains. Interactions between two FitB molecules result in the
      formation of a tetramer of FitAB heterodimers, which binds to the 36-bp DNA
      fragment and provides an explanation for how FitB enhances the DNA binding
      affinity of FitA.

PMID- 16982616
TI  - Three complement-like repeats compose the complete alpha2-macroglobulin binding
      site in the second ligand binding cluster of the low density lipoprotein receptor
      related protein.
AB  - Given the importance of the low density lipoprotein receptor-related protein
      (LRP) as an essential endocytosis and signaling receptor for many protein
      ligands, and of alpha2-macroglobulin (alpha2M)-proteinase complexes as one such
      set of ligands, an understanding of the specificity of their interaction with LRP
      is an important goal. A starting point is the known role of the 138-residue
      receptor binding domain (RBD) in binding to LRP. Previous studies have localized
      high affinity alpha2M binding to the eight complement repeat (CR)-containing
      cluster 2 of LRP. In the present study we have identified the minimum CR domains
      that constitute the full binding site for RBD and, hence, for alpha2M on LRP. We
      report on the ability of the triple construct of CR3-4-5 to bind RBD with an
      affinity (Kd = 130 nM) the same as for isolated RBD to intact LRP. This Kd is 30
      fold smaller than for RBD to CR5-6-7, demonstrating the specificity of the
      interaction with CR3-4-5. Binding requires previously identified critical lysine
      residues but is almost pH-independent within the range of pH values encountered
      between extracellular and internal compartments, consistent with an earlier
      proposed model of intracellular ligand displacement by intramolecular YWTD
      domains. The present findings suggest a model to explain the ability of LRP to
      bind a wide range of structurally unrelated ligands in which a nonspecific ligand
      interaction with the acidic region present in most CR domains is augmented by
      interactions with other CR surface residues that are unique to a particular CR
      cluster.

PMID- 16982617
TI  - A conserved subtilisin protease identified in Babesia divergens merozoites.
AB  - Invasion of erythrocytes is an integral part of the Babesia divergens life cycle.
      Serine proteases have been shown to play an important role in invasion by related
      Apicomplexan parasites such as the malaria parasite Plasmodium falciparum. Here
      we demonstrate the presence of two dominant serine proteases in asexual B.
      divergens using a biotinylated fluorophosphonate probe. One of these active
      serine proteases (p48) and its precursors were recognized by anti-PfSUB1
      antibodies. These antibodies were used to clone the gene encoding a serine
      protease using a B. divergens cDNA library. BdSub-1 is a single copy gene with no
      introns. The deduced gene product (BdSUB-1) clearly belongs to the subtilisin
      superfamily and shows significant homology to Plasmodium subtilisins, with the
      highest degree of sequence identity around the four catalytic residues. Like
      subtilisin proteases in other Apicomplexan parasites, BdSUB-1 undergoes two steps
      of processing during activation in the secretory pathway being finally converted
      to an active form (p48). The mature protease is concentrated in merozoite dense
      granules, apical secretory organelles involved in erythrocyte invasion. Anti
      PfSUB1 antibodies have a potent inhibitory effect on erythrocyte invasion by B.
      divergens merozoites in vitro. This report demonstrates conservation of the
      molecular machinery involved in erythrocyte invasion by these two Apicomplexan
      parasites and paves the way for a comparative analysis of other molecules that
      participate in this process in the two parasites.

PMID- 16982618
TI  - Mu opioid receptor activation of ERK1/2 is GRK3 and arrestin dependent in
      striatal neurons.
AB  - In this study we investigated the mechanisms responsible for MAP kinase ERK1/2
      activation following agonist activation of endogenous mu opioid receptors (MOR)
      normally expressed in cultured striatal neurons. Treatment with the MOR agonist
      fentanyl caused significant activation of ERK1/2 in neurons derived from wild
      type mice. Fentanyl effects were blocked by the opioid antagonist naloxone and
      were not evident in neurons derived from MOR knock-out (-/-) mice. In contrast,
      ERK1/2 activation by fentanyl was not evident in neurons from GRK3-/- mice or
      neurons pretreated with small inhibitory RNA for arrestin3. Consistent with this
      observation, treatment with the opiate morphine (which is less able to activate
      arrestin) did not elicit ERK1/2 activation in wild type neurons; however,
      transfection of arrestin3-(R170E) (a dominant positive form of arrestin that does
      not require receptor phosphorylation for activation) enabled morphine activation
      of ERK1/2. In addition, activation of ERK1/2 by fentanyl and morphine was rescued
      in GRK3-/- neurons following transfection with dominant positive arrestin3
      (R170E). The activation of ERK1/2 appeared to be selective as p38 MAP kinase
      activation was not increased by either fentanyl or morphine treatment in neurons
      from wild type, MOR-/-, or GRK3-/- mice. In addition, U0126 (a selective
      inhibitor of MEK kinase responsible for ERK phosphorylation) blocked ERK1/2
      activation by fentanyl. These results support the hypothesis that MOR activation
      of ERK1/2 requires opioid receptor phosphorylation by GRK3 and association of
      arrestin3 to initiate the cascade resulting in ERK1/2 phosphorylation in striatal
      neurons.

PMID- 16982619
TI  - Bmi-1 regulates the differentiation and clonogenic self-renewal of I-type
      neuroblastoma cells in a concentration-dependent manner.
AB  - Human neuroblastoma I-type cells have been proposed as a population of malignant
      neural crest stem cells, based on their high tumorigenic potential, expression of
      stem cell markers, and ability to differentiate into cells of neural crest
      lineages, including neuroblastic (N-type) and Schwann/glial (S-type) cells. Here,
      we demonstrate at single cell levels that a subpopulation of I-type cells possess
      clonogenic self-renewal capacity that requires the Polycomb group family
      transcription repressor Bmi-1. We further show that Bmi-1 expression levels exert
      an instructive influence on lineage commitment by I-type cells. Spontaneous and
      induced differentiation of I-type cells into S-type cells is accompanied by a
      marked reduction in the level of Bmi-1 expression, and enforced down-regulation
      of BMI-1 facilitates spontaneous differentiation of I-type cells into S-type
      cells. By contrast, N-type neuroblastoma cell lines and differentiated N-type
      cells express higher levels of Bmi-1 relative to I-type cells, and overexpression
      of BMI-1 promotes the differentiation of I-type cells along the neuronal lineage.
      Thus, Bmi-1 acts in a concentration-dependent manner in the control of the
      delicate balance between the self-renewal and differentiation of neuroblastoma I
      type cells. These observations suggest that graded activation of a master
      regulator within individual tumors could trigger divergent developmental programs
      responsible for both tumor growth and heterogeneity.

PMID- 16982620
TI  - Ultra-efficient replication of infectious prions by automated protein misfolding
      cyclic amplification.
AB  - Prions are the unconventional infectious agents responsible for transmissible
      spongiform encephalopathies, which appear to be composed mainly or exclusively of
      the misfolded prion protein (PrPSc). Prion replication involves the conversion of
      the normal prion protein (PrPC) into the misfolded isoform, catalyzed by tiny
      quantities of PrPSc present in the infectious material. We have recently
      developed the protein misfolding cyclic amplification (PMCA) technology to
      sustain the autocatalytic replication of infectious prions in vitro. Here we show
      that PMCA enables the specific and reproducible amplification of exceptionally
      minute quantities of PrPSc. Indeed, after seven rounds of PMCA, we were able to
      generate large amounts of PrPSc starting from a 1x10(-12) dilution of scrapie
      hamster brain, which contains the equivalent of approximately 26 molecules of
      protein monomers. According to recent data, this quantity is similar to the
      minimum number of molecules present in a single particle of infectious PrPSc,
      indicating that PMCA may enable detection of as little as one oligomeric PrPSc
      infectious particle. Interestingly, the in vitro generated PrPSc was infectious
      when injected in wild-type hamsters, producing a disease identical to the one
      generated by inoculation of the brain infectious material. The unprecedented
      amplification efficiency of PMCA leads to a several billion-fold increase of
      sensitivity for PrPSc detection as compared with standard tests used to screen
      prion-infected cattle and at least 4000 times more sensitivity than the animal
      bioassay. Therefore, PMCA offers great promise for the development of highly
      sensitive, specific, and early diagnosis of transmissible spongiform
      encephalopathy and to further understand the molecular basis of prion
      propagation.

PMID- 16982621
TI  - ATP from subplasmalemmal mitochondria controls Ca2+-dependent inactivation of
      CRAC channels.
AB  - A sustained Ca2+ entry is the primary signal for T lymphocyte activation after
      antigen recognition. This Ca2+ entry mainly occurs through store-operated Ca2+
      channels responsible for a highly selective Ca2+ current known as I(CRAC). Ca2+
      ions act as negative feedback regulators of I(CRAC), promoting its inactivation.
      Mitochondria, which act as intracellular Ca2+ buffers, have been proposed to
      control all stages of CRAC current and, hence, intracellular Ca2+ signaling in
      several types of non-excitable cells. Using the whole-cell configuration of the
      patch clamp technique, which allows control of the intracellular environment, we
      report here that respiring mitochondria located close to CRAC channels can
      regulate slow Ca2+-dependent inactivation of I(CRAC) by increasing the Ca2+
      buffering capacity beneath the plasma membrane, mainly through the release of
      ATP.

PMID- 16982622
TI  - Identification and functional characterization of a monofunctional peroxisomal
      enoyl-CoA hydratase 2 that participates in the degradation of even cis
      unsaturated fatty acids in Arabidopsis thaliana.
AB  - A gene, named AtECH2, has been identified in Arabidopsis thaliana to encode a
      monofunctional peroxisomal enoyl-CoA hydratase 2. Homologues of AtECH2 are
      present in several angiosperms belonging to the Monocotyledon and Dicotyledon
      classes, as well as in a gymnosperm. In vitro enzyme assays demonstrated that
      AtECH2 catalyzed the reversible conversion of 2E-enoyl-CoA to 3R-hydroxyacyl-CoA.
      AtECH2 was also demonstrated to have enoyl-CoA hydratase 2 activity in an in vivo
      assay relying on the synthesis of polyhydroxyalkanoate from the polymerization of
      3R-hydroxyacyl-CoA in the peroxisomes of Saccharomyces cerevisiae. AtECH2
      contained a peroxisome targeting signal at the C-terminal end, was addressed to
      the peroxisome in S. cerevisiae, and a fusion protein between AtECH2 and a
      fluorescent protein was targeted to peroxisomes in onion cells. AtECH2 gene
      expression was strongest in tissues with high beta-oxidation activity, such as
      germinating seedlings and senescing leaves. The contribution of AtECH2 to the
      degradation of unsaturated fatty acids was assessed by analyzing the carbon flux
      through the beta-oxidation cycle in plants that synthesize peroxisomal
      polyhydroxyalkanoate and that were over- or underexpressing the AtECH2 gene.
      These studies revealed that AtECH2 participates in vivo to the conversion of the
      intermediate 3R-hydroxyacyl-CoA, generated by the metabolism of fatty acids with
      a cis (Z)-unsaturated bond on an even-numbered carbon, to the 2E-enoyl-CoA for
      further degradation through the core beta-oxidation cycle.

PMID- 16982623
TI  - Nickel compounds render anti-apoptotic effect to human bronchial epithelial Beas
      2B cells by induction of cyclooxygenase-2 through an IKKbeta/p65-dependent and
      IKKalpha- and p50-independent pathway.
AB  - The carcinogenicity of nickel compounds has been well documented both in vitro
      and in vivo; however, the molecular mechanisms by which nickel compounds cause
      cancers are far from understood. Because suppression of apoptosis is thought to
      contribute to carcinogenesis, we investigated the mechanisms implicated in nickel
      induced anti-apoptotic effect in human bronchial epithelial (Beas-2B) cells. We
      found that exposure of Beas-2B cells to nickel compounds resulted in increased
      cyclooxygenase-2 (COX-2) expression and that small interfering RNA (siCOX-2)
      knockdown of COX-2 expression resulted in increased cell sensitivity to nickel
      triggered cell apoptosis, demonstrating that COX-2 induction has an anti
      apoptotic effect on Beas-2B cells. Overexpression of IKKbeta-KM, a kinase
      inactive mutant of IKKbeta, blocked NF-kappaB activation and COX-2 induction by
      nickel compounds, indicating that activated NF-kappaB may be a mediator for COX-2
      induction. To further explore the contribution of the NF-kappaB pathway in COX-2
      induction and in protection from nickel exposure, mouse embryonic fibroblasts
      deficient in IKKbeta, IKKalpha, p65, and p50 were analyzed. Loss of IKKbeta
      impaired COX-2 induction by nickel exposure, whereas knockout of IKKalpha had a
      marginal effect. Moreover, the NF-kappaB p65, and not the p50 subunit, was
      critical for nickel-induced COX-2 expression. In addition, a deficiency of
      IKKbeta or p65 rendered cells more sensitive to nickel-induced apoptosis as
      compared with those in wild type cells. Finally, it was shown that reactive
      oxygen species H(2)O(2) were involved in both NF-kappaB activation and COX-2
      expression. Collectively, our results demonstrate that COX-2 induction by nickel
      compounds occurs via an IKKbeta/p65 NF-kappaB-dependent but IKKalpha- and p50
      independent pathway and plays a crucial role in antagonizing nickel-induced cell
      apoptosis in Beas-2B cells.

PMID- 16982624
TI  - The "linker" region (amino acids 38-47) of the disintegrin elegantin is a novel
      inhibitory domain of integrin alpha5beta1-dependent cell adhesion on fibronectin:
      evidence for the negative regulation of fibronectin synergy site biological
      activity.
AB  - Disintegrins are a family of potent inhibitors of cell-cell and cell-matrix
      adhesion. In this study we have identified a region of the disintegrin elegantin,
      termed the "linker domain" (amino acids 38-47), with inhibitory activity toward
      alpha(5)beta(1)-mediated cell adhesion on fibronectin (Fn). Using a chimeric
      structure-function approach in which sequences of the functionally distinct
      disintegrin kistrin were introduced into the elegantin template at targeted
      sites, a loss of inhibitory function toward alpha(5)beta(1)-mediated adhesion on
      Fn was observed when the elegantin linker domain was substituted. Subsequent
      analysis comparing the inhibitory efficacies of the panel of elegantin-kistrin
      chimeras toward CHO alpha(5) cell adhesion on recombinant Fn III(6-10) fragments
      showed that the loss of inhibitory activity associated with the disruption of the
      elegantin linker domain was dependent upon the presence of a functional Fn III(9)
      synergy site within the Fn III(6-10) substrate. This suggested that the elegantin
      linker domain inhibits primarily the activity of the Fn synergy domain in
      promoting alpha(5)beta(1) integrin-mediated cell adhesion. Construction of a
      cyclic peptide corresponding to the entire region of the elegantin linker domain
      showed that this domain has intrinsic alpha(5)beta(1) inhibitory activity
      comparable with the activity of the RGDS peptide. These data demonstrate a novel
      biological function for a disintegrin domain that antagonizes integrin-mediated
      cell adhesion.

PMID- 16982625
TI  - Identification of Tctex2beta, a novel dynein light chain family member that
      interacts with different transforming growth factor-beta receptors.
AB  - Endoglin is a membrane-inserted protein that is preferentially synthesized in
      angiogenic vascular endothelial and smooth muscle cells. Endoglin associates with
      members of the transforming growth factor-beta (TGF-beta) receptor family and has
      been identified as the gene involved in hereditary hemorrhagic telangiectasia.
      Although endoglin is known to affect cell responses to TGF-beta, its mode of
      action is largely unknown. We performed yeast two-hybrid screening of a human
      placental cDNA library and isolated a new endoglin-binding partner, a novel 221
      amino acid member of the Tctex1/2 family of cytoplasmic dynein light chains named
      Tctex2beta, as the founder of a new Tctex1/2 subfamily. The interaction was
      localized exclusively to the cytoplasmic domain of endoglin. Reverse
      transcription-PCR showed expression of Tctex2beta in a wide range of tissues,
      including vascular endothelial and smooth muscle cells, placenta, and testis, as
      well as in several tumor cell lines. High expression levels were found in human
      umbilical vein endothelial cells and the large cell lung cancer cell line. Forced
      expression of Tctex2beta had a profound inhibitory effect on TGF-beta signaling.
      Additional Tctex2beta-interacting receptors were identified to be the TGF-beta
      type II receptor and most likely beta-glycan, but not ALK5, ALK1, or the bone
      morphogenetic protein type II receptor. Upon fluorescence tagging, co
      localization of Tctex2beta and endoglin, as well as Tctex2beta, endoglin, and the
      TGF-beta type II receptor, was observed by different microscopy techniques. Our
      findings link endoglin for the first time to microtubule-based minus end-directed
      transport machinery, suggesting that some endoglin functions might be regulated
      and directed by its interaction with the cytoplasmic dynein light chain
      Tctex2beta.

PMID- 16982626
TI  - Suppression of cancer cell migration and invasion by protein phosphatase 2A
      through dephosphorylation of mu- and m-calpains.
AB  - The mu- and m-calpains are major members of the calpain family that play an
      essential role in regulating cell motility. We have recently discovered that
      nicotine-activated protein kinase C iota enhances calpain phosphorylation in
      association with enhanced calpain activity and accelerated migration and invasion
      of human lung cancer cells. Here we found that specific disruption of protein
      phosphatase 2A (PP2A) activity by expression of SV40 small tumor antigen up
      regulates phosphorylation of mu- and m-calpains whereas C2-ceramide, a potent
      PP2A activator, reduces nicotine-induced calpain phosphorylation, suggesting that
      PP2A may function as a physiological calpain phosphatase. PP2A co-localizes and
      interacts with mu- and m-calpains. Purified, active PP2A directly
      dephosphorylates mu- and m-calpains in vitro. Overexpression of the PP2A
      catalytic subunit (PP2A/C) suppresses nicotine-stimulated phosphorylation of mu-
      and m-calpains, which is associated with inhibition of calpain activity, wound
      healing, cell migration, and invasion. By contrast, depletion of PP2A/C by RNA
      interference enhances calpain phosphorylation, calpain activity, cell migration,
      and invasion. Importantly, C2-ceramide-induced suppression of calpain
      phosphorylation results in decreased secretion of mu- and m-calpains from lung
      cancer cells into culture medium, which may have potential clinic relevance in
      controlling metastasis of lung cancer. These findings reveal a novel role for
      PP2A as a physiological calpain phosphatase that not only directly
      dephosphorylates but also inactivates mu- and m-calpains, leading to suppression
      of migration and invasion of human lung cancer cells.

PMID- 16982627
TI  - Redox regulation of 4-hydroxy-2-nonenal-mediated endothelial barrier dysfunction
      by focal adhesion, adherens, and tight junction proteins.
AB  - 4-Hydroxy-2-nonenal (4-HNE), one of the major biologically active aldehydes
      formed during inflammation and oxidative stress, has been implicated in a number
      of cardiovascular and pulmonary disorders. 4-HNE has been shown to increase
      vascular endothelial permeability; however, the underlying mechanisms are
      unclear. Hence, in the current study, we tested our hypothesis that 4-HNE-induced
      changes in cellular thiol redox status may contribute to modulation of cell
      signaling pathways that lead to endothelial barrier dysfunction. Exposure of
      bovine lung microvascular endothelial cells (BLMVECs) to 4-HNE induced reactive
      oxygen species generation, depleted intracellular glutathione, and altered cell
      cell adhesion as measured by transendothelial electrical resistance. Pretreatment
      of BLM-VECs with thiol protectants, N-acetylcysteine and mercaptopropionyl
      glycine, attenuated 4-HNE-induced decrease in transendothelial electrical
      resistance, reactive oxygen species generation, Michael protein adduct formation,
      protein tyrosine phosphorylation, activation of ERK, JNK, and p38 MAPK, and actin
      cytoskeletal rearrangement. Treatment of BLMVECs with 4-HNE resulted in the
      redistribution of FAK, paxillin, VE-cadherin, beta-catenin, and ZO-1, and
      intercellular gap formation. Western blot analyses confirmed the formation of 4
      HNE-derived Michael adducts with the focal adhesion and adherens junction
      proteins. Also, 4-HNE decreased tyrosine phosphorylation of FAK without affecting
      total cellular FAK contents, suggesting the modification of integrins, which are
      natural FAK receptors. 4-HNE caused a decrease in the surface integrin in a time
      dependent manner without altering total alpha5 and beta3 integrins. These
      results, for the first time, revealed that 4-HNE in redox-dependent fashion
      affected endothelial cell permeability by modulating cell-cell adhesion through
      focal adhesion, adherens, and tight junction proteins as well as integrin signal
      transduction that may lead dramatic alteration in endothelial cell barrier
      dysfunction during heart infarction, brain stroke, and lung diseases.

PMID- 16982628
TI  - Proteolytically processed soluble tumor endothelial marker (TEM) 5 mediates
      endothelial cell survival during angiogenesis by linking integrin alpha(v)beta3
      to glycosaminoglycans.
AB  - Tumor endothelial marker (TEM) 5 is a member of the adhesion family of G-protein
      coupled receptors and up-regulated in endothelial cells during tumor and
      physiologic angiogenesis. Here, we report that TEM5 is expressed on the surface
      of endothelial cells. A soluble TEM5 (sTEM5) fragment is shed by endothelial
      cells during capillary-like network formation and upon growth factor stimulation.
      We found that sTEM5 binds to several glycosaminoglycans. Furthermore, sequence
      analysis and functional and biochemical studies revealed that sTEM5 contains a
      cryptic RGD-binding site for integrin alpha(v)beta3. Matrix metalloprotease 9
      processed, but not full-length, sTEM5 mediated endothelial cell adhesion by
      direct interaction with integrin alpha(v)beta3. Adhesion to proteolytically
      processed sTEM5 (ppsTEM5) or glycosaminoglycan-bound ppsTEM5 promoted survival of
      growth factor deprived endothelial cells. ppsTEM5-mediated cell survival was
      inhibited by a function blocking integrin alpha(v)beta3 antibody. Based on our
      results we conclude that sTEM5 is shed by endothelial cells during angiogenesis
      and binds to glycosaminoglycans present on extracellular matrix and cell surface
      proteoglycans. Further proteolytic processing of sTEM5 leads to exposure of its
      RGD motif mediating endothelial cell survival by linking integrin alpha(v)beta3
      to glycosaminoglycans.

PMID- 16982629
TI  - Functional characterization of the N-terminal region of myosin-2.
AB  - All class 2 myosins contain an N-terminal extension of approximately 80 residues
      that includes an Src homology 3 (SH3)-like subdomain. To explore the functional
      importance of this region, which is also present in most other myosin classes, we
      generated truncated constructs of Dictyostelium discoideum myosin-2. Truncation
      at position 80 resulted in the complete loss of myosin-2 function in vivo. Actin
      affinity was more than 80-fold, and the rate of ADP release approximately 40-fold
      decreased in this mutant. In contrast, a myosin construct that lacks only the SH3
      like subdomain, corresponding to residues 33-79, displayed much smaller
      functional defects. In complementation experiments with myosin-2 null cells, this
      construct rescued myosin-2-dependent processes such as cytokinesis, fruiting body
      formation, and sporogenesis. An 8-fold reduction in motile activity and changes
      of similar extent in the affinity for ADP and filamentous actin indicate the
      importance of the SH3-like subdomain for correct communication between the
      functional regions within the myosin motor domain and suggest that local
      perturbations in this region can play a role in modulating myosin-2 motor
      activity.

PMID- 16982630
TI  - Angiotensin II-induced NADPH oxidase activation impairs insulin signaling in
      skeletal muscle cells.
AB  - The renin-angiotensin system (RAS) and reactive oxygen species (ROS) have been
      implicated in the development of insulin resistance and its related
      complications. There is also evidence that angiotensin II (Ang II)-induced
      generation of ROS contributes to the development of insulin resistance in
      skeletal muscle, although the precise mechanisms remain unknown. In the present
      study, we found that Ang II markedly enhanced NADPH oxidase activity and
      consequent ROS generation in L6 myotubes. These effects were blocked by the
      angiotensin II type 1 receptor blocker losartan, and by the NADPH oxidase
      inhibitor apocynin. Ang II also promoted the translocation of NADPH oxidase
      cytosolic subunits p47phox and p67phox to the plasma membrane within 15 min.
      Furthermore, Ang II abolished insulin-induced tyrosine phosphorylation of insulin
      receptor substrate 1 (IRS1), activation of protein kinase B (Akt), and glucose
      transporter-4 (GLUT4) translocation to the plasma membrane, which was reversed by
      pretreating myotubes with losartan or apocynin. Finally, small interfering RNA
      (siRNA)-specific gene silencing targeted specifically against p47phox (p47siRNA),
      in both L6 and primary myotubes, reduced the cognate protein expression,
      decreased NADPH oxidase activity, restored Ang II-impaired IRS1 and Akt
      activation as well as GLUT4 translocation by insulin. These results suggest a
      pivotal role for NADPH oxidase activation and ROS generation in Ang II-induced
      inhibition of insulin signaling in skeletal muscle cells.

PMID- 16982631
TI  - Light chain tubulopathy without Fanconi syndrome.

PMID- 16982632
TI  - Tissue factor and its inhibitor in human non-crescentic glomerulonephritis-
      immunostaining vs plasma and urinary levels.
AB  - BACKGROUND: Tissue factor (TF)-the most potent trigger of coagulation and
      emerging antiapoptotic, proliferative and angiogenic factor, along with its
      principal inhibitor (tissue factor pathway inhibitor, TFPI) are known to be
      involved in crescentic glomerulonephritis (GN). We studied the relationship
      between plasma and urinary levels as well as renal biopsy immunostaining of TF
      and TFPI antigens with reference to some clinical parameters in human chronic non
      crescentic GN. METHODS: We examined plasma and urinary levels of TF and total
      TFPI (pre-biopsy, ELISA) and the intensity of TF, TFPI 1 and TFPI 2 staining
      (immunoperoxidase histochemistry) in kidney biopsy specimens from 30 chronic GN
      patients. RESULTS: Plasma and urinary TF (uTF) were higher in patients than in 18
      healthy individuals. In normal kidneys, TF and TFPI 1/2 antigens were
      undetectable in glomeruli while a distinct staining of both TFPI variants was
      observed in tubules and interstitial microvessels. In diseased kidneys, TF was
      strongly expressed in glomeruli but was undetectable in tubules. In contrast,
      staining for TFPI 1/2 was observed in glomeruli and tubules. Neither plasma nor
      urinary levels of the markers correlated with the intensity of TF and TFPI 1/2
      staining in biopsy specimens. uTF was significantly associated with creatinine
      clearance (R = 0.489, P = 0.006) and urinary TFPI (R = 0.554, P = 0.014), and
      tended to be lower in proliferative vs non-proliferative GN [83 (0-617) vs 281
      (10-805) pg/ml; P = 0.06]. CONCLUSION: The intrarenal TF/TFPI system is
      profoundly disturbed in chronic GN. Plasma and urinary concentrations of TF and
      TFPI probably do not reflect genuine activity of the disease, likely due to a
      confounding effect of kidney insufficiency. uTF measurement seems to be helpful
      in initial identification of proliferative GN, yet further studies are required
      to validate its use as a marker of glomerular injury in chronic GN.

PMID- 16982633
TI  - Changes in fat mass after initiation of maintenance dialysis is influenced by the
      uncoupling protein 2 exon 8 insertion/deletion polymorphism.
AB  - BACKGROUND: A high body mass index (BMI) has been reported to confer a survival
      advantage in end-stage renal disease (ESRD) patients. On the other hand, body fat
      accumulation, especially visceral adipose tissue, is an important risk factor for
      cardiovascular disease, as well as a clinically important source of adipokines.
      Uncoupling protein 2 (UCP2) uncouples respiration from ATP synthesis, thus
      regulating energy expenditure and fat oxidation. In this longitudinal cohort
      study, we investigated the impact of the UCP2 insertion/deletion (ins/del)
      polymorphism on body composition changes in ESRD patients starting dialysis.
      METHODS: A total of 222 incident Caucasian ESRD patients (mean age 53 +/- 12
      years; 60% males) were investigated close to the start of dialysis with
      peritoneal dialysis (PD; n = 126) or haemodialysis (HD; n = 96), and again after
      about 1 year (n = 159). Genotyping of the UCP2 ins/del polymorphism was performed
      in the patients and in 207 healthy controls. Dual-energy X-ray absorptiometry was
      conducted at baseline and after 1 year to monitor body composition. RESULTS:
      While HD patients and PD patients with the ins/del genotype did not display any
      changes in body composition, the 48 PD patients with the del/del genotype that
      completed follow-up had a significant increase; DeltaBMI (0.7 +/- 1.8 kg/m(2)),
      Deltabody fat mass (3.5 +/- 3.8 kg) and Deltatruncal fat mass (1.7 +/- 1.2 kg).
      In a multiple linear regression analysis, the del/del genotype was an independent
      predictor of the increase in truncal fat mass in PD patients (F-ratio = 7.99, P <
      0.05) together with age and diabetes mellitus. CONCLUSIONS: PD patients, but not
      HD patients, with the UCP2 del/del genotype showed a significant increase in
      total and truncal fat mass during the first year of dialysis therapy, suggesting
      a possible role for UCP2 in dissipating the excess energy of a high-glucose
      environment.

PMID- 16982634
TI  - The reverse epidemiology of plasma total homocysteine as a mortality risk factor
      is related to the impact of wasting and inflammation.
AB  - BACKGROUND: The reason(s) for the apparently paradoxical 'reverse' association in
      end-stage renal disease (ESRD) patients in whom a low, rather than a high, total
      plasma total homocysteine (tHcy) level is an indicator of poor outcome remains
      unclear. The aim of this study was to examine whether the inverse association
      maintains, mitigates or reverses after comprehensive multivariate adjustment for
      the presence of wasting and inflammation as well as other potential confounders.
      METHODS: We studied 317 ESRD patients starting dialysis therapy. Fasting blood
      samples were taken for the analyses of tHcy, serum albumin, C-reactive protein
      (CRP), serum creatinine and plasma folate. Nutritional status was assessed by
      subjective global assessment (SGA). Survival was followed for up to 66 months;
      105 patients died. RESULTS: Using Kaplan-Meier analysis, a low tHcy concentration
      (< or =30 micromol/l) was associated with higher all-cause and cardiovascular
      (CV) mortality (P < 0.05). Using Cox proportional analysis adjusting for age,
      gender, glomerular filtration rate = GFR, cardiovascular disease = CVD, plasma
      folate, total cholesterol and diabetes mellitus, the all-cause and CV mortality
      still tended to be high for patients with low tHcy. Adding nutritional and
      inflammation markers (Body mass index = BMI, SGA, serum creatinine, serum albumin
      and CRP), a low tHcy level was no longer associated with higher mortality but a
      trend for high tHcy was observed. CONCLUSIONS: The link between wasting
      inflammation and a low tHcy appears to be responsible for the reverse association
      between plasma tHcy and clinical outcome in ESRD patients. After adjustment for
      confounders including nutritional and inflammation markers, a trend towards
      increased death risk for high, rather than low, tHcy levels was apparent after
      adjustment.

PMID- 16982635
TI  - Risk factors associated with body mass index increase in men at 28 years follow
      up.
AB  - BACKGROUND: Several studies have reported a general increase in body mass index
      (BMI). AIM: To identify factors influencing BMI changes at 28 years follow-up.
      DESIGN: Prospective screening study. METHODS: The cohort of the Oslo I study of
      1972/73 had another screening in 2000 (Oslo II). We present data for these men,
      and men from Oslo I who participated in five similar studies during 1996-2001. In
      all, 7157 men aged 20-49 years at first screening attended two health screenings,
      and complete data were available for 7104. BMI change from 1972/73 to 2000 was
      the dependent variable in multiple regression analyses. RESULTS: The percentage
      with obesity (BMI > or = 30) increased overall from 2.5% to 13.5%. The overall
      mean (SD) BMI increased from 24.2 (2.6) kg/m2 to 26.2 (3.4) kg/m2. The increase
      was largest (3.9 (2.5) kg/m2) among men aged 20-24 in 1972/73 and least (1.6
      (2.5) kg/m2) in those aged 45-49 years. No age trend was observed for those with
      BMI > or = 30.0 kg/m2 in 1972/3. On multiple regression analysis, increasing
      triglycerides, systolic blood pressure, age and non-fasting glucose, decreasing
      physical activity and not smoking were all significantly related to increasing
      BMI. Having stopped smoking was also related to increased BMI. Daily smoking in
      both 1972/73 and 2000, and daily smoking in 2000 but not in 1972/73, were
      inversely related to increased BMI. DISCUSSION: There was a substantial increase
      in BMI, with the largest increase in the younger men, except in those who were
      already obese at first screening. Overall, obesity increased by 11% in the study
      period and was associated with multiple life-style factors.

PMID- 16982636
TI  - Loeffler endomyocardial fibrosis.

PMID- 16982637
TI  - Binding of human SLBP on the 3'-UTR of histone precursor H4-12 mRNA induces
      structural rearrangements that enable U7 snRNA anchoring.
AB  - In metazoans, cell-cycle-dependent histones are produced from poly(A)-lacking
      mRNAs. The 3' end of histone mRNAs is formed by an endonucleolytic cleavage of
      longer precursors between a conserved stem-loop structure and a purine-rich
      histone downstream element (HDE). The cleavage requires at least two trans-acting
      factors: the stem-loop binding protein (SLBP), which binds to the stem-loop and
      the U7 snRNP, which anchors to histone pre-mRNAs by annealing to the HDE. Using
      RNA structure-probing techniques, we determined the secondary structure of the 3'
      untranslated region (3'-UTR) of mouse histone pre-mRNAs H4-12, H1t and H2a-614.
      Surprisingly, the HDE is embedded in hairpin structures and is therefore not
      easily accessible for U7 snRNP anchoring. Probing of the 3'-UTR in complex with
      SLBP revealed structural rearrangements leading to an overall opening of the
      structure especially at the level of the HDE. Electrophoretic mobility shift
      assays demonstrated that the SLBP-induced opening of HDE actually facilitates U7
      snRNA anchoring on the histone H4-12 pre-mRNAs 3' end. These results suggest that
      initial binding of the SLBP functions in making the HDE more accessible for U7
      snRNA anchoring.

PMID- 16982638
TI  - PhenomicDB: a new cross-species genotype/phenotype resource.
AB  - Phenotypes are an important subject of biomedical research for which many
      repositories have already been created. Most of these databases are either
      dedicated to a single species or to a single disease of interest. With the advent
      of technologies to generate phenotypes in a high-throughput manner, not only is
      the volume of phenotype data growing fast but also the need to organize these
      data in more useful ways. We have created PhenomicDB (freely available at
      http://www.phenomicdb.de), a multi-species genotype/phenotype database, which
      shows phenotypes associated with their corresponding genes and grouped by gene
      orthologies across a variety of species. We have enhanced PhenomicDB recently by
      additionally incorporating quantitative and descriptive RNA interference (RNAi)
      screening data, by enabling the usage of phenotype ontology terms and by
      providing information on assays and cell lines. We envision that integration of
      classical phenotypes with high-throughput data will bring new momentum and
      insights to our understanding. Modern analysis tools under development may help
      exploiting this wealth of information to transform it into knowledge and,
      eventually, into novel therapeutic approaches.

PMID- 16982639
TI  - XE7: a novel splicing factor that interacts with ASF/SF2 and ZNF265.
AB  - Pre-mRNA splicing is performed by the spliceosome. SR proteins in this
      macromolecular complex are essential for both constitutive and alternative
      splicing. By using the SR-related protein ZNF265 as bait in a yeast two-hybrid
      screen, we pulled out the uncharacterized human protein XE7, which is encoded by
      a pseudoautosomal gene. XE7 had been identified in a large-scale proteomic
      analysis of the human spliceosome. It consists of two different isoforms produced
      by alternative splicing. The arginine/serine (RS)-rich region in the larger of
      these suggests a role in mRNA processing. Herein we show for the first time that
      XE7 is an alternative splicing regulator. XE7 interacts with ZNF265, as well as
      with the essential SR protein ASF/SF2. The RS-rich region of XE7 dictates both
      interactions. We show that XE7 localizes in the nucleus of human cells, where it
      colocalizes with both ZNF265 and ASF/SF2, as well as with other SR proteins, in
      speckles. We also demonstrate that XE7 influences alternative splice site
      selection of pre-mRNAs from CD44, Tra2-beta1 and SRp20 minigenes. We have thus
      shown that the spliceosomal component XE7 resembles an SR-related splicing
      protein, and can influence alternative splicing.

PMID- 16982640
TI  - Examination of the structural and functional versatility of glmS ribozymes by
      using in vitro selection.
AB  - Self-cleaving ribozymes associated with the glmS genes of many Gram-positive
      bacteria are activated by binding to glucosamine-6-phosphate (GlcN6P).
      Representatives of the glmS ribozyme class function as metabolite-sensing
      riboswitches whose self-cleavage activities down-regulate the expression of GlmS
      enzymes that synthesizes GlcN6P. As with other riboswitches, natural glmS
      ribozyme isolates are highly specific for their target metabolite. Other small
      molecules closely related to GlcN6P, such as glucose-6-phosphate, cannot activate
      self-cleavage. We applied in vitro selection methods in an attempt to identify
      variants of a Bacillus cereus glmS ribozyme that expand the range of compounds
      that induce self-cleavage. In addition, we sought to increase the number of
      variant ribozymes of this class to further examine the proposed secondary
      structure model. Although numerous variant ribozymes were obtained that
      efficiently self-cleave, none exhibited changes in target specificity. These
      findings are consistent with the hypothesis that GlcN6P is used by the ribozyme
      as a coenzyme for RNA cleavage, rather than an allosteric effector.

PMID- 16982641
TI  - Genetic regulation of fluxes: iron homeostasis of Escherichia coli.
AB  - Iron is an essential trace-element for most organisms. However, because high
      concentration of free intracellular iron is cytotoxic, cells have developed
      complex regulatory networks that keep free intracellular iron concentration at
      optimal range, allowing the incorporation of the metal into iron-using enzymes
      and minimizing damage to the cell. We built a mathematical model of the network
      that controls iron uptake and usage in the bacterium Escherichia coli to explore
      the dynamics of iron flow. We simulate the effect of sudden decrease or increase
      in the extracellular iron level on intracellular iron distribution. Based on the
      results of simulations we discuss the possible roles of the small RNA RyhB and
      the Fe-S cluster assembly systems in the optimal redistribution of iron flows. We
      suggest that Fe-S cluster assembly is crucial to prevent the accumulation of
      toxic levels of free intracellular iron when the environment suddenly becomes
      iron rich.

PMID- 16982642
TI  - Sequence-specific binding of single-stranded RNA: is there a code for
      recognition?
AB  - A code predicting the RNA sequence that will be bound by a certain protein based
      on its amino acid sequence or its structure would provide a useful tool for the
      design of RNA binders with desired sequence-specificity. Such de novo designed
      RNA binders could be of extraordinary use in both medical and basic research
      applications. Furthermore, a code could help to predict the cellular functions of
      RNA-binding proteins that have not yet been extensively studied. A comparative
      analysis of Pumilio homology domains, zinc-containing RNA binders, hnRNP K
      homology domains and RNA recognition motifs is performed in this review. Based on
      this, a set of binding rules is proposed that hints towards a code for RNA
      recognition by these domains. Furthermore, we discuss the intermolecular
      interactions that are important for RNA binding and summarize their importance in
      providing affinity and specificity.

PMID- 16982643
TI  - A peptide with alternating lysines can act as a highly specific Z-DNA binding
      domain.
AB  - Many nucleic acid binding proteins use short peptide sequences to provide
      specificity in recognizing their targets, which may be either a specific sequence
      or a conformation. Peptides containing alternating lysine have been shown to bind
      to poly(dG-d5meC) in the Z conformation, and stabilize the higher energy form [H.
      Takeuchi, N. Hanamura, H. Hayasaka and I. Harada (1991) FEBS Lett., 279, 253-255
      and H. Takeuchi, N. Hanamura and I. Harada (1994) J. Mol. Biol., 236, 610-617.].
      Here we report the construction of a Z-DNA specific binding protein, with the
      peptide KGKGKGK as a functional domain and a leucine zipper as a dimerization
      domain. The resultant protein, KGZIP, induces the Z conformation in poly(dG
      d5meC) and binds to Z-DNA stabilized by bromination with high affinity and
      specificity. The binding of KGZIP is sufficient to convert poly(dG-d5meC) from
      the B to the Z form, as shown by circular dichroism. The sequence KGKGKGK is
      found in many proteins, although no functional role has been established. KGZIP
      also has potential for engineering other Z-DNA specific proteins for future
      studies of Z-DNA in vitro and in vivo.

PMID- 16982644
TI  - AccuTyping: new algorithms for automated analysis of data from high-throughput
      genotyping with oligonucleotide microarrays.
AB  - Microarray-based analysis of single nucleotide polymorphisms (SNPs) has many
      applications in large-scale genetic studies. To minimize the influence of
      experimental variation, microarray data usually need to be processed in different
      aspects including background subtraction, normalization and low-signal filtering
      before genotype determination. Although many algorithms are sophisticated for
      these purposes, biases are still present. In the present paper, new algorithms
      for SNP microarray data analysis and the software, AccuTyping, developed based on
      these algorithms are described. The algorithms take advantage of a large number
      of SNPs included in each assay, and the fact that the top and bottom 20% of SNPs
      can be safely treated as homozygous after sorting based on their ratios between
      the signal intensities. These SNPs are then used as controls for color channel
      normalization and background subtraction. Genotype calls are made based on the
      logarithms of signal intensity ratios using two cutoff values, which were
      determined after training the program with a dataset of approximately 160,000
      genotypes and validated by non-microarray methods. AccuTyping was used to
      determine >300,000 genotypes of DNA and sperm samples. The accuracy was shown to
      be >99%. AccuTyping can be downloaded from
      http://www2.umdnj.edu/lilabweb/publications/AccuTyping.html.

PMID- 16982645
TI  - Computational analysis of tissue-specific combinatorial gene regulation:
      predicting interaction between transcription factors in human tissues.
AB  - Tissue-specific gene expression is generally regulated by more than a single
      transcription factor (TF). Multiple TFs work in concert to achieve tissue
      specificity. In order to explore these complex TF interaction networks, we
      performed a large-scale analysis of TF interactions for 30 human tissues. We
      first identified tissue-specific genes for 30 tissues based on gene expression
      databases. We then evaluated the relationships between TFs using the relative
      position and co-occurrence of their binding sites in the promoters of tissue
      specific genes. The predicted TF-TF interactions were validated by both known
      protein-protein interactions and co-expression of their target genes. We found
      that our predictions are enriched in known protein-protein interactions (>80
      times that of random expectation). In addition, we found that the target genes
      show the highest co-expression in the tissue of interest. Our findings
      demonstrate that non-tissue specific TFs play a large role in regulation of
      tissue-specific genes. Furthermore, they show that individual TFs can contribute
      to tissue specificity in different tissues by interacting with distinct TF
      partners. Lastly, we identified several tissue-specific TF clusters that may play
      important roles in tissue-specific gene regulation.

PMID- 16982646
TI  - A set of nearest neighbor parameters for predicting the enthalpy change of RNA
      secondary structure formation.
AB  - A complete set of nearest neighbor parameters to predict the enthalpy change of
      RNA secondary structure formation was derived. These parameters can be used with
      available free energy nearest neighbor parameters to extend the secondary
      structure prediction of RNA sequences to temperatures other than 37 degrees C.
      The parameters were tested by predicting the secondary structures of sequences
      with known secondary structure that are from organisms with known optimal growth
      temperatures. Compared with the previous set of enthalpy nearest neighbor
      parameters, the sensitivity of base pair prediction improved from 65.2 to 68.9%
      at optimal growth temperatures ranging from 10 to 60 degrees C. Base pair
      probabilities were predicted with a partition function and the positive
      predictive value of structure prediction is 90.4% when considering the base pairs
      in the lowest free energy structure with pairing probability of 0.99 or above.
      Moreover, a strong correlation is found between the predicted melting
      temperatures of RNA sequences and the optimal growth temperatures of the host
      organism. This indicates that organisms that live at higher temperatures have
      evolved RNA sequences with higher melting temperatures.

PMID- 16982648
TI  - Identification of a structural and functional domain in xNAP1 involved in protein
      protein interactions.
AB  - xNAP1 (Xenopus nucleosome assembly protein) belongs to the family of nucleosome
      assembly proteins (NAPs) and shares 92% identity with human and mouse NAP1. NAPs
      have been reported to have a role in nucleosome assembly, cell cycle regulation,
      cell proliferation and transcriptional control, although the precise function of
      NAP1 is still not clear. Here we report the identification of a putative domain
      of xNAP1 by limited proteolysis. This domain has been mapped in the xNAP1 protein
      sequence to residues 38-282 and thus lacks the acidic sequences at the N- and C
      termini. We have studied this domain and related fragments in vitro and by a
      functional assay involving over-expression of the protein in Xenopus laevis
      embryos. Analytical ultracentrifugation shows that removal of the acidic N- and C
      terminal regions does not prevent the formation of larger multimers, which are
      predominantly hexadecamers. Injection of mRNA encoding the full-length xNAP1 or
      the putative domain and other related constructs into Xenopus embryos gave
      identical phenotypes. These results are discussed in relation to protein-protein
      interactions between NAP1 octamers and a possible 'squelching' mechanism.

PMID- 16982647
TI  - Controlling activation of the RNA-dependent protein kinase by siRNAs using site
      specific chemical modification.
AB  - The RNA-dependent protein kinase (PKR) is activated by binding to double-stranded
      RNA (dsRNA). Activation of PKR by short-interfering RNAs (siRNAs) and stimulation
      of the innate immune response has been suggested to explain certain off-target
      effects in some RNA interference experiments. Here we show that PKR's kinase
      activity is stimulated in vitro 3- to 5-fold by siRNA duplexes with 19 bp and 2
      nt 3'-overhangs, whereas the maximum activation observed for poly(I)*poly(C) was
      17-fold over background under the same conditions. Directed hydroxyl radical
      cleavage experiments indicated that siRNA duplexes have at least four different
      binding sites for PKR's dsRNA binding motifs (dsRBMs). The location of these
      binding sites suggested specific nucleotide positions in the siRNA sense strand
      that could be modified with a corresponding loss of PKR binding. Modification at
      these sites with N2-benzyl-2'-deoxyguanosine (BndG) blocked interaction with
      PKR's dsRBMs and inhibited activation of PKR by the siRNA. Importantly,
      modification of an siRNA duplex that greatly reduced PKR activation did not
      prevent the duplex from lowering mRNA levels of a targeted message by RNA
      interference in HeLa cells. Thus, these studies demonstrate that specific
      positions in an siRNA can be rationally modified to prevent interaction with
      components of cellular dsRNA-regulated pathways.

PMID- 16982649
TI  - Evaluation of a nutrition education intervention for women residents of
      Washington, DC, public housing communities.
AB  - We designed, implemented and evaluated an educational intervention to increase
      fruit and vegetable consumption among urban African-American women. Women aged 20
      50 years (n=212) from 11 public housing communities participated in seven 90-min
      classes with a professional nutritionist. Our prospective pre- and post-test
      design, with 4-month follow-up, assessed the relationship between attendance and
      dietary change, using three 24-hour recalls per time point. Mean change in
      average daily dietary values for fruits and vegetables, calories and percent
      calories from fat (post-test versus pre-test, follow-up versus pre-test) was
      compared by class attendance, to evaluate the impact of class attendance on
      dietary change. Attendance varied from zero (35%) to five to seven classes (42%).
      Baseline dietary recalls showed average daily consumption of 3.05 servings of
      fruits and vegetables, 2416 calories and 35.8% calories from fat. No improvements
      in fruit and vegetable consumption, but statistically significant decreases in
      total calories and percent calories from fat, were seen at both endpoints. Women
      attending five to seven classes had the greatest dietary improvements, averaging,
      at post-test and follow-up, respectively, 246.2 and 324.5 fewer calories and 3.08
      and 2.97% fewer calories from fat. Results suggest that, for some residents of
      low-resource communities, small group interventions are popular, effective
      vehicles for nutrition education.

PMID- 16982650
TI  - Out of context? Translating evidence from the North Karelia project over place
      and time.
AB  - Within the literature on community-based heart health promotion and chronic
      disease prevention, the North Karelia project is often viewed as a model program
      for achieving community-wide reductions in risk factors and mortality associated
      with cardiovascular disease. In the present study, we examine the tendency to
      attempt replication of elements of the North Karelia project, without due
      consideration of the unique population and setting being targeted. We analysed a
      sample of 64 articles reporting on community-based interventions targeting
      chronic disease, published between 1990 and 2002. Of these 64 articles, 43 (67%)
      made explicit reference to North Karelia or one of the other early projects
      (Stanford, Minnesota, Pawtucket). Of these 43 articles, 8 (19%) explicitly
      acknowledged the unique features of the population/setting in question, and
      articulated a need to adapt to these unique features, while 10 (23%) provided no
      acknowledgment of unique population/setting features. The remaining 25 (58%) were
      'in between', and examples from each group are discussed. We conclude that for
      many contemporary community-based interventions, concern with replicating the
      North Karelia project is accompanied by inadequate consideration or reporting of
      the details of the unique context (including people, place and time), and this
      may undermine the success of community-based health promotion.

PMID- 16982651
TI  - Physiological responses of potato (Solanum tuberosum L.) to partial root-zone
      drying: ABA signalling, leaf gas exchange, and water use efficiency.
AB  - The physiological responses of potato (Solanum tuberosum L. cv. Folva) to partial
      root-zone drying (PRD) were investigated in potted plants in a greenhouse (GH)
      and in plants grown in the field under an automatic rain-out-shelter. In the GH,
      irrigation was applied daily to the whole root system (FI), or to one-half of the
      root system while the other half was dried, for 9 d. In the field, the plants
      were drip irrigated either to the whole root system near field capacity (FI) or
      using 70% water of FI to one side of the roots, and shifted to the other side
      every 5-10 d (PRD). PRD plants had a similar midday leaf water potential to that
      of FI, whereas in the GH their root water potential (Psi(r)) was significantly
      lowered after 5 d. Stomatal conductance (g(s)) was more sensitive to PRD than
      photosynthesis (A) particularly in the field, leading to greater intrinsic water
      use efficiency (WUE) (i.e. A/g(s)) in PRD than in FI plants on several days. In
      PRD, the xylem sap abscisic acid concentration ([ABA](xylem)) increased
      exponentially with decreasing Psi(r); and the relative [ABA](xylem) (PRD/FI)
      increased exponentially as the fraction of transpirable soil water (FTSW) in the
      drying side decreased. In the field, the leaf area index was slightly less in PRD
      than in FI treatment, while tuber biomass was similar for the two treatments.
      Compared with FI, PRD treatment saved 30% water and increased crop water use
      efficiency (WUE) by 59%. Restrictions on leaf area expansion and g(s) by PRD
      induced ABA signals might have contributed to reduced water use and increased
      WUE.

PMID- 16982652
TI  - Dynamic analysis of ABA accumulation in relation to the rate of ABA catabolism in
      maize tissues under water deficit.
AB  - The plant hormone abscisic acid (ABA) accumulates in plant tissues which
      experience water deficit (stress ABA). This study analysed its accumulation as a
      function of both synthesis and catabolism in maize tissues. By following the
      disappearance of the stress ABA when ABA synthesis was blocked by
      nordihydroguaiaretic acid (NDGA), the rate of the catabolism of stress ABA was
      determined. When compared with the catabolic rate of baseline (non-stress) ABA,
      stress ABA showed a catabolic rate >11 times higher. With such an elevated
      catabolic rate, it is proposed that the xanthophyll precursor pool may not be
      able to sustain the ABA accumulation, and such a proposition has been
      substantiated by further experiments where fluridone is used to limit the
      availability of upstream ABA precursors. When fluridone was used, stress ABA
      accumulation could only be sustained for a few hours, i.e. approximately 5 h for
      leaf and 1 h for root tissues. In detached roots, stress ABA accumulation could
      not be sustained even if fluridone was not used, suggesting that stress ABA
      accumulation in root systems requires the continuous import of ABA precursors
      from the shoots. Such an assumption was substantiated by the observation that
      defoliation or shading significantly reduced ABA accumulation in intact roots.
      The present study suggests that ABA catabolism is rapid enough to play an
      important role in the regulation of ABA accumulation.

PMID- 16982653
TI  - Dynamics of spatial heterogeneity of stomatal closure in Tradescantia virginiana
      altered by growth at high relative air humidity.
AB  - The spatial heterogeneity of stomatal closure in response to rapid desiccation of
      excised well-watered Tradescantia virginiana leaves grown at moderate (55%) or
      high (90%) relative air humidity (RH) was studied using a chlorophyll
      fluorescence imaging system under non-photorespiratory conditions. Following
      rapid desiccation, excised leaves grown at high RH had both a greater
      heterogeneity and a higher average value of PSII efficiency (Phi(PSII)) compared
      with leaves grown at moderate RH. Larger decreases in relative water content
      resulted in smaller decreases in water potential and Phi(PSII) of high RH-grown
      leaves compared with moderate RH-grown leaves. Moreover, the Phi(PSII) of excised
      high RH-grown leaves decreased less with decreasing water potential, implying
      that the stomata of high RH-grown leaves are less sensitive to decreases in leaf
      water potential compared with moderate RH-grown leaves. After desiccation, some
      non-closing stomata were distributed around the main vein in high RH-grown
      leaves. Direct measurements of stomatal aperture showed 77% stomatal closure in
      the margins after 2 h desiccation compared with 40% closure of stomata in the
      main-vein areas in high RH-grown leaves. Faster closure of stomata in leaf
      margins compared with main-vein areas of leaves grown at high RH was related to
      substantially lower relative water content in these areas of the leaves.

PMID- 16982654
TI  - Cerebellar damage impairs detection of somatosensory input changes. A
      somatosensory mismatch-negativity study.
AB  - Several recent studies support the view that the cerebellum's contribution to
      sensory processing is not limited to movement regulation. In a previous paper
      (Restuccia D, Valeriani M, Barba C, Le Pera D, Capecci M, Filippini V, Molinari
      M. Functional changes of the primary somatosensory cortex in patients with
      unilateral cerebellar lesions. Brain 2001; 124: 757-68) we showed that the
      cerebellum influences somatosensory input processing at very early stages. The
      present study was aimed at verifying whether an analogous influence is also
      exerted at higher levels. For some time it has been known that in the auditory
      modality a specific event-related potential (ERP), that is, mismatch negativity
      (MMN), reflects preattentive detection of changes in the incoming stimulus by
      comparing the new stimulus with sensory memory traces. To test the cerebellar
      influence on the processing of incoming somatosensory stimuli we first verified
      whether the electrical stimulation of fingers, according to an 'oddball' paradigm
      within a stimulus-ignored condition, was able to elicit event-related components
      specifically linked to the preattentive detection of change. We analysed scalp
      responses obtained from eight healthy volunteers during frequent and rare
      electrical stimulation of the first and fifth finger of the left hand,
      respectively. To ensure that responses to deviant stimuli were due to changes in
      detection mechanisms, rather than to activation of new afferents, we also
      analysed responses to rare stimulation alone ('standard-omitted' condition). The
      'oddball' stimulation was able to elicit a parieto-occipital extra negativity
      that was different in scalp distribution and latency from the N140 response to
      the 'standard-omitted' stimulation. We considered that this response was related
      to changes in detection mechanisms and labelled it somatosensory mismatch
      negativity (S-MMN). When the same procedure was applied to six patients with
      unilateral cerebellar lesions we found that the S-MMN was clearly abnormal after
      stimulation of the affected hand (ipsilateral to the affected cerebellar
      hemisphere). Earlier ERPs, as well as ERPs elicited during the 'standard-omitted'
      condition, were fully normal. Present data indicate that cerebellar processing is
      involved in preattentive detection of somatosensory input changes. In conclusion,
      this study demonstrates the reliability of S-MMN recordings and indicates that
      subjects with cerebellar damage may be impaired in the cortical processing of
      incoming somatosensory inputs.

PMID- 16982655
TI  - Multi-disciplinary centres/networks of excellence for endometriosis management
      and research: a proposal.
AB  - Centres/networks of excellence are the only way forward to ensure that women with
      endometriosis receive consistent, evidence-based care, ensuring excellence,
      continuity of care, multi-disciplinarity, research, training and cost
      effectiveness. Clinical excellence should be achieved by proper training,
      adherence to evidence-based guidelines, quality management and continuous
      measurement of patient outcome as a central focus. To ensure continuity of care,
      the first step is to assign to each patient a central gynaecologist who must have
      continuously updated knowledge regarding all diagnostic and management options
      for endometriosis and who must set priorities and realistic expectations together
      with the woman using a long-term multi-disciplinary treatment plan. Scientific
      research within and scientific collaboration between centres/networks of
      excellence will create the critical mass of patients and tissue samples that is
      needed to make progress. Centres/networks of excellence should be accredited as
      training centres by professional bodies. They should aim at improving the cost
      effectiveness of the management of endometriosis by a reduction in the time to
      diagnosis, a reduction in the time before individualized specialist care is
      invoked, a reduction of expensive hit-and-miss treatments and a reduction in
      expensive fertility treatments, if the disease is under control before fertility
      is impaired.

PMID- 16982656
TI  - Effects of ageing on spermatozoal chromatin and its sensitivity to in vivo and in
      vitro oxidative challenge in the Brown Norway rat.
AB  - BACKGROUND: The goals of our study were to examine chromatin packaging and
      integrity in spermatozoa taken from the caput and cauda epididymides of young (4
      month-old) and old (21-month-old) Brown Norway rats and to assess whether
      spermatozoal sensitivity to oxidative treatments is altered with age. METHODS:
      Oxidative treatments consisted of (i) in vivo oxidative challenge by systemic
      administration of the glutathione-depleting drug l-buthionine-[S,R]-sulphoximine
      (BSO) and (ii) in vitro oxidative challenge by incubating collected spermatozoa
      with hydrogen peroxide (H(2)O(2)). Chromatin parameters assessed included
      quantification of thiols, nuclear chromomycin A3 (CMA3) penetration, DNA breaks
      by TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling
      (TUNEL) and ease of DNA dissociation by acridine orange (AO) staining. RESULTS:
      In spermatozoa from older rats, we found decreases in thiols, CMA3 penetration
      and the percentage of cells that undergo DNA dissociation. Administration of BSO
      had oxidizing effects on the thiol groups. It also decreased CMA3 penetration and
      DNA dissociation and increased TUNEL staining. Furthermore, BSO treatment
      sensitized cauda epididymidis spermatozoa, from older animals, to H(2)O(2).
      CONCLUSIONS: Overall, we show that spermatozoa from older rats have altered
      chromatin packaging and integrity and that spermatozoa from the cauda
      epididymidis are more responsive to combined in vivo and in vitro oxidative
      challenge than spermatozoa from young rats.

PMID- 16982657
TI  - Toll-like receptor 4 polymorphisms and idiopathic chromosomally normal
      miscarriage.
AB  - BACKGROUND: Lipopolysaccharide (LPS or endotoxin) exposure resulting from
      microbial invasion of the endometrium disturbs the Th1/Th2 balance at the feto
      maternal interface and has been linked to the risk of idiopathic miscarriage in a
      range of human and animal studies. Toll-like receptor 4 (TLR4) mediates LPS
      signalling, and the human TLR4 gene harbours two single-nucleotide polymorphisms
      (SNPs) known to reduce LPS responsiveness. We hypothesized that genetic variation
      altering TLR4 function may influence the risk of idiopathic pregnancy loss.
      METHODS AND RESULTS: We examined fetal TLR4 genotypes in a case-control cohort of
      chromosomally normal miscarriages (n=96) and healthy term newborns (n=113). The
      allele frequencies of the Asp299Gly and Thr399Ile TLR4 SNPs were determined by
      quantitative PCR using DNA extracted from extraembryonic tissues and umbilical
      cord blood, respectively. TLR4 genotype frequencies were not significantly
      different between cases and controls. CONCLUSIONS: There was no association
      between fetal TLR4 polymorphisms, Asp299Gly and Thr399Ile, known to blunt LPS
      responsiveness, and the risk of idiopathic, chromosomally normal miscarriage.
      Nevertheless, TLR4 or perhaps other LPS-binding chaperone molecules are
      biologically plausible candidate genes that may alter the risk of idiopathic
      miscarriage.

PMID- 16982658
TI  - Patient-centred care: using online personal medical records in IVF practice.
AB  - BACKGROUND: Generic patient-accessible medical records have shown promise in
      enhancing patient-centred care for patients with chronic diseases. We sought to
      design, implement and evaluate a patient-accessible medical record specifically
      for patients undergoing a course of assisted reproduction (IVF or ICSI). METHODS:
      The personal medical record (PMR) database was developed using three formative
      evaluation steps, and its user-experience was evaluated through a cross-sectional
      study. Fifty-four patient-couples receiving an IVF or ICSI treatment in our
      hospital were granted access to the PMR. Main outcomes concern the usage of the
      PMR, the perceived usefulness of its functions and user attitudes towards privacy
      and financial issues. RESULTS: The PMR consists of 15 major functions that can be
      classified into personal information, general information and communication
      functions. Fifty-three patient-couples accessed the website and 51 couples filled
      out the evaluation questionnaire. They rated most functions as useful and
      preferred personalized to general functions. The results also show that some
      functions require further development. Patients using the PMR have little
      concerns regarding privacy, and 76% are willing to pay for such a service in the
      future. CONCLUSIONS: The patients in this study frequently and intensively used
      the Internet-accessible PMR. This suggests that the PMR offers very useful
      functions from an IVF/ICSI patient's perspective.

PMID- 16982659
TI  - Medical outcome of 8-year-old singleton ICSI children (born >or=32 weeks'
      gestation) and a spontaneously conceived comparison group.
AB  - BACKGROUND: There is little information about the long-term outcome of children
      born after ICSI. In this study, the eldest cohort of ICSI children worldwide,
      reaching the age of 8 years, was investigated at the prepubertal stage to monitor
      subsequent puberty and future fertility. To investigate possible health problems,
      a thorough medical and neurological examination was performed. METHODS: Medical
      outcome of 8-year-old singletons (n=150) born through ICSI (>or=32 weeks) was
      compared with that of 147 singletons of the same age born after spontaneous
      conception (SC). Information about their general health was obtained from the
      parents by means of a questionnaire. RESULTS: Fifteen of 150 ICSI children
      experienced a major congenital malformation compared with 5/147 SC children (P <
      0.05). Pubertal staging was similar in both groups. Neurological examination did
      not show important differences between ICSI and SC children. ICSI children did
      not require more remedial therapy or surgery or hospitalization than SC children.
      CONCLUSION: Physical examination including a thorough neurological examination
      did not reveal important differences between the two groups. Major congenital
      malformations were significantly more frequent in the ICSI group. However, most
      of them were corrected by minor surgery. Further monitoring of these children at
      an older age is recommended.

PMID- 16982660
TI  - Novel direct cover vitrification for cryopreservation of ovarian tissues
      increases follicle viability and pregnancy capability in mice.
AB  - BACKGROUND: Cryopreservation of ovarian tissue is valuable for fertility
      preservation. We develop an innovative vitrification method using less
      concentrated cryoprotectants and direct application of liquid nitrogen to the
      ovarian tissue (direct cover vitrification, DCV) to improve its efficiency.
      METHODS: Ovaries of 5- to 6-week-old C57BL/6J mice were randomly allocated to
      four groups: DCV, conventional vitrification, slow-freezing and non-frozen
      controls. Experiment 1: observing the follicle morphology. Experiment 2:
      assessing viability. Experiment 3: investigating the ultrastructure. Experiment
      4: examining the follicle number after grafting. Experiment 5: ascertaining
      pregnancy potential by allogeneic orthotopic transplantation. RESULTS: The
      percentages of morphologically normal or viable follicles from DCV were
      significantly greater than those achieved from conventional vitrification and
      slow freezing (P < 0.01). The ultrastructure of primordial follicles from DCV
      appeared better than that achieved from conventional vitrification and slow
      freezing. After grafting, the follicle number from DCV was greater than
      conventional vitrification (P = 0.001) and slow freezing (P = 0.021). The
      pregnancy rate of DCV was higher than conventional vitrification (P < 0.01). The
      litter size from DCV was comparable with that from non-frozen graft and was
      significantly greater than that achieved from conventional vitrification and slow
      freezing (P < 0.01). CONCLUSIONS: DCV is highly efficient for cryopreservation of
      ovarian tissue. Using less concentrated cryoprotectants appears to reduce
      toxicity. Direct cover by liquid nitrogen maximizes cooling that could facilitate
      vitrification and prevent ice crystal injury.

PMID- 16982661
TI  - The contradictory information on the distribution of non-disjunction and pre
      division in female gametes.
AB  - Valuable information on the cytogenetic constitution of female gametes has been
      deduced from the direct, so-called conventional analysis of oocytes remaining
      unfertilized in programmes of assisted reproduction. Additional, indirect
      conclusions have become possible by PGD of the polar bodies. Both techniques
      provided evidence for the co-existence of two aneuploidy-causing mechanisms
      during first maternal meiosis; non-disjunction (ND) of bivalents results in the
      loss or gain of whole chromosomes in metaphase II complements, whereas a
      precocious division (pre-division, PD) of univalents leads to the loss or gain of
      single chromatids. As to the distribution of ND and PD, however, direct oocyte
      chromosome studies and PGD tell surprisingly different stories. Moreover, first
      and second polar body analyses contradict the data derived from DNA polymorphism
      studies concerning the distribution of first and second meiotic division errors.
      An increased awareness of these problems appears necessary because important
      decisions are made on the basis of PGD results.

PMID- 16982662
TI  - Morphologic parameters of early cleavage-stage embryos that correlate with fetal
      development and delivery: prospective and applied data for increased pregnancy
      rates.
AB  - BACKGROUND: Many different embryo selection criteria have been used in assisted
      reproductive technologies (ART), but there are no published prospective studies
      to ascertain their usefulness in predicting implantation. METHODS: In a
      prospective trial, 20 early scoring parameters previously reported to influence
      clinical outcome were collected, but embryos were selected for transfer by
      current laboratory protocols; day 1 pronuclear (PN) (Z) score combined with day 3
      or 5 morphology. Data points for each oocyte/embryo were scored independently and
      tracked individually. Data were analysed retrospectively for parameters most
      likely to result in a positive pregnancy test, fetal heartbeat (FHB) and
      delivery. RESULTS: Results indicated that day 1 PN morphology and nucleolar
      precursor body (NPB) ratio, day 2 cell number, blastomere symmetry and nucleation
      and the ability to cleave from day 2 to day 3 were the six most significant
      factors in fetal development. This outcome was then applied prospectively over 8
      months. The implantation rate (IR) and clinical pregnancy rate (CPR) increased in
      each age group, and the number of embryos used decreased. CONCLUSION: In
      conclusion, early parameters that include PN morphology, number and ratio of NPBs
      per nucleus and the day 2 morphology of cleaving embryos are stronger positive
      predictors of implantation than day 3 morphology or the ability to achieve the
      blastocyst stage of development. Parameters that were most consistently
      correlated with no delivery were lack of PN symmetry, day 2 multinucleation and
      uneven cell size. Day 3 and day 5 parameters were not significant compared with
      the combination of early parameters.

PMID- 16982663
TI  - Gangliosides as components of lipid membrane domains.
AB  - Cell membrane components are organized as specialized domains involved in
      membrane-associated events such as cell signaling, cell adhesion, and protein
      sorting. These membrane domains are enriched in sphingolipids and cholesterol but
      display a low protein content. Theoretical considerations and experimental data
      suggest that some properties of gangliosides play an important role in the
      formation and stabilization of specific cell lipid membrane domains. Gangliosides
      are glycolipids with strong amphiphilic character and are particularly abundant
      in the plasma membranes, where they are inserted into the external leaflet with
      the hydrophobic ceramide moiety and with the oligosaccharide chain protruding
      into the extracellular medium. The geometry of the monomer inserted into the
      membrane, largely determined by the very large surface area occupied by the
      oligosaccharide chain, the ability of the ceramide amide linkage to form a
      network of hydrogen bonds at the water-lipid interface of cell membranes, the
      Delta(4) double bond of sphingosine proximal to the water-lipid interface, the
      capability of the oligosaccharide chain to interact with water, and the absence
      of double bonds into the double-tailed hydrophobic moiety are the ganglioside
      features that will be discussed in this review, to show how gangliosides are
      responsible for the formation of cell lipid membrane domains characterized by a
      strong positive curvature.

PMID- 16982664
TI  - Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage
      in older people.
AB  - Cerebral amyloid angiopathy (CAA) is an important cause of primary intracerebral
      haemorrhage (PICH) in older people, accounting for approximately 10% of all types
      of PICH. The amount of amyloid deposition in the vessels and vasculopathic
      changes determine the propensity to PICH. The risk factors of CAA include
      advanced age and the presence of certain alleles of apolipoprotein E. There are
      no specific clinical features of CAA-related PICH, although lobar, recurrent or
      multiple simultaneous haemorrhages in older patients should raise suspicion of
      its diagnosis. A definitive diagnosis of CAA requires pathological examination of
      the affected tissue. However, with modern imaging techniques, it is possible to
      make a diagnosis of 'probable CAA' in patients presenting with PICH. Gradient
      echo magnetic resonance imaging is a sensitive, non-invasive technique for
      identifying small haemorrhages in life. Currently, there is no specific treatment
      available for CAA. Recent advances in the immunopathology and pathogenesis of CAA
      are expected to help in developing specific anti-amyloid therapy.

PMID- 16982665
TI  - Pharmacist-led medication reviews can reduce patient morbidity?

PMID- 16982666
TI  - Cholecalciferol, not ergocalciferol, should be used for vitamin D
      supplementation.

PMID- 16982667
TI  - Endometrial receptivity markers, the journey to successful embryo implantation.
AB  - Human embryo implantation is a three-stage process (apposition, adhesion and
      invasion) involving synchronized crosstalk between a receptive endometrium and a
      functional blastocyst. This ovarian steroid-dependent phenomenon can only take
      place during the window of implantation, a self-limited period of endometrial
      receptivity spanning between days 20 and 24 of the menstrual cycle. Implantation
      involves a complex sequence of signalling events, consisting in the acquisition
      of adhesion ligands together with the loss of inhibitory components, which are
      crucial to the establishment of pregnancy. Histological evaluation, now
      considered to add little clinically significant information, should be replaced
      by functional assessment of endometrial receptivity. A large number of molecular
      mediators have been identified to date, including adhesion molecules, cytokines,
      growth factors, lipids and others. Thus, endometrial biopsy samples can be used
      to identify molecules associated with uterine receptivity to obtain a better
      insight into human implantation. In addition, development of functional in vitro
      systems to study embryo-uterine interactions will lead to better definition of
      the interactions existing between the molecules involved in this process. The
      purpose of this review was not only to describe the different players of the
      implantation process but also to try to portray the relationship between these
      factors and their timing in the process of uterine receptivity.

PMID- 16982668
TI  - Internal genetic structure and outcrossing rate in a natural population of
      Araucaria angustifolia (Bert.) O. Kuntze.
AB  - The internal genetic structure and outcrossing rate of a population of Araucaria
      angustifolia (Bert.) O. Kuntze were investigated using 16 allozyme loci.
      Estimates of the mean number of alleles per loci (1.6), percentage of polymorphic
      loci (43.8%), and expected genetic diversity (0.170) were similar to those
      obtained for other gymnosperms. The analysis of spatial autocorrelation
      demonstrated the presence of internal structure in the first distance classes (up
      to 70 m), suggesting the presence of family structure. The outcrossing rate was
      high (0.956), as expected for a dioecious species. However, it was different from
      unity, indicating outcrossings between related individuals and corroborating the
      presence of internal genetic structure. The results of this study have
      implications for the methodologies used in conservation collections and for the
      use or analysis of this forest species.

PMID- 16982669
TI  - A method for identification of the expression mode and mapping of QTL underlying
      embryo-specific characters.
AB  - Embryos of crop seeds are one of the major sources of the plant protein and lipid
      for human nutrition. The genetic expression for embryo-specific characters in
      crop seeds can be controlled exclusively by the embryo or the maternal genotypes
      and sometimes by both simultaneously. However, current methods for mapping
      quantitative trait loci (QTLs) underlying characters of maternal plants have not
      been effective in dealing with the QTL analysis of embryo characters. On the
      basis of the expression feature of embryo, a statistical method was proposed for
      the identification of expression mode and mapping of QTL controlling embryo
      traits. The maximum likelihood method implemented via the expectation
      maximization algorithm was used to estimate parameters of a putative embryo
      specific QTL. The QTL expression mode was identified by the likelihood ratio test
      statistic. Statistical power and other properties of the proposed method were
      investigated under a variety of scenarios through simulation studies. The results
      showed that the mapping method neglecting the effects of embryo genotype or
      maternal effects could neither identify the expression mode of QTL nor estimate
      its genetic effects accurately, whereas the proposed method could effectively map
      the embryo-specific QTL of various expression modes.

PMID- 16982670
TI  - Generation means analysis of climbing ability in common bean (Phaseolus vulgaris
      L.).
AB  - Climbing common bean (Phaseolus vulgaris L.) genotypes have among the highest
      yield potential of all accessions found in the species. Genetic improvement of
      climbing beans would benefit from an understanding of the inheritance of climbing
      capacity (made up of plant height [PH] and internode length [IL] traits). The
      objective of this study was to determine the inheritance of climbing capacity
      traits in 3 crosses made within and between gene pools (Andean x Andean [BRB32 x
      MAC47], Mesoamerican x Mesoamerican [Tio Canela x G2333], and Mesoamerican x
      Andean [G2333 x G19839]) using generation means analysis. For each population, we
      used 6 generations (P(1), P(2), F(1), F(2), BC(1)P(1), and BC(1)P(2)) that were
      evaluated at 2 growth stages (40 and 70 days after planting). Results showed the
      importance of additive compared with the dominant-additive portion of the genetic
      model. Broad-sense heritabilities for the traits varied from 62.3% to 85.6% for
      PH and from 66.5% to 83.7% for IL. The generation means analysis and estimates of
      heritability suggested that the inheritance of PH and IL in climbing beans is
      relatively simple.

PMID- 16982671
TI  - Airway responses in Brown Norway rats following inhalation sensitization and
      challenge with trimellitic anhydride.
AB  - Trimellitic anhydride (TMA) is a cause of asthma in man. Dose-dependent TMA
      specific IgE, histopathology, and airway responses after sensitization by
      inhalation were examined in the Brown Norway rat. Rats were exposed to 0.04, 0.4,
      4, or 40 mg/m3 TMA aerosol for 10 min, once a week, over 10 weeks. All lower
      exposures were, subsequently, rechallenged to 40 mg/m3 TMA aerosol. All rats
      received a sham exposure 1 week prior to the first TMA exposure. Following the
      sham exposure and weekly after each TMA exposure, TMA-specific IgE and both early
      phase airway response (EAR) and late-phase airway response (LAR) were measured
      using enhanced pause (Penh). All rats sensitized by 40 mg/m3 TMA developed
      specific IgE, EAR, and LAR to one or more of the challenges to 40 mg/m3 TMA. TMA
      of 4 mg/m3 induced a much lower, but stable, specific IgE response. EAR and LAR
      were observed only after a 40 mg/m3 TMA rechallenge in this group, but it was
      much larger than that observed in the 40 mg/m3 TMA-sensitized and challenged
      group. Exposure-dependent histopathological changes noted included eosinophilic
      granulomatous interstitial pneumonia, perivascular eosinophil infiltrates,
      bronchial-associated lymphoid tissue hyperplasia, and peribronchiolar plasma cell
      infiltrates.

PMID- 16982672
TI  - Coffee and sweetened beverage consumption and the risk of type 2 diabetes
      mellitus: the atherosclerosis risk in communities study.
AB  - The authors analyzed data from a prospective, community-based cohort to assess
      the risk of incident type 2 diabetes mellitus associated with coffee and
      sweetened beverage consumption. They included 12,204 nondiabetic, middle-aged men
      and women in the Atherosclerosis Risk in Communities (ARIC) Study (1987-1999).
      Consumption of each beverage was assessed by food frequency questionnaire and
      classified into categories of cups per day. They found an inverse association,
      after adjusting for potential confounders, between increased coffee consumption
      and risk of type 2 diabetes mellitus in men (for > or =4 cups (> or =0.95
      liter)/day compared with almost never: hazard ratio = 0.77, p(trend) = 0.02) with
      no significant association in women (hazard ratio = 0.89, p(trend) = 0.32) using
      a combination of self-report of physician-diagnosed diabetes, diabetes treatment,
      and a fasting or nonfasting blood glucose test. When self-reported diabetes or
      diabetes treatment alone was used, a stronger and significant inverse association
      was seen in men and women. Sweetened beverage consumption (men: hazard ratio =
      1.03, p(trend) = 0.94; women: hazard ratio = 1.01, p(trend) = 0.58) showed no
      consistent association with the incidence of type 2 diabetes mellitus. In
      summary, increased coffee consumption was significantly associated with a
      decreased risk of diagnosed type 2 diabetes mellitus in community-based US
      adults.

PMID- 16982673
TI  - Identification of clinically significant tumor antigens by selecting phage
      antibody library on tumor cells in situ using laser capture microdissection.
AB  - Much work has been done to develop tumor-targeting antibodies by selecting a
      phage antibody library on cancer cell lines. However, when tumor cells are
      removed from their natural environment, they may undergo genetic and epigenetic
      changes yielding different surface antigens than those seen in actual cases of
      cancer. We developed a strategy that allows selection of phage antibodies against
      tumor cells in situ on both fresh frozen and paraffin-embedded tissues using
      laser capture microdissection. By restricting antibody selection to binders of
      internalizing epitopes, we generated a panel of phage antibodies that target
      clinically represented prostate cancer antigens. We identified ALCAM/MEMD/CD166,
      a newly discovered prostate cancer marker, as the target for one of the selected
      antibodies, demonstrating the effectiveness of our approach. We further
      conjugated two single chain Fv fragments to liposomes and demonstrated that these
      nanotargeting devices were efficiently delivered to the interior of prostate
      cancer cells. The ability to deliver payload intracellularly and to recognize
      tumor cells in situ makes these antibodies attractive candidates for the
      development of targeted cancer therapeutics.

PMID- 16982674
TI  - A network-based analysis of polyanion-binding proteins utilizing yeast protein
      arrays.
AB  - The high affinity of certain cellular polyanions for many proteins (polyanion
      binding proteins (PABPs)) has been demonstrated previously. It has been
      hypothesized that such polyanions may be involved in protein structure
      stabilization, stimulation of folding through chaperone-like activity, and intra-
      and extracellular protein transport as well as intracellular organization. The
      purpose of the proteomics studies reported here was to seek evidence for the idea
      that the nonspecific but high affinity interactions of PABPs with polyanions have
      a functional role in intracellular processes. Utilizing yeast protein arrays and
      five biotinylated cellular polyanion probes (actin, tubulin, heparin, heparan
      sulfate, and DNA), we identified proteins that interact with these probes and
      analyzed their structural and amino acid sequence requirements as well as their
      predicted functions in the yeast proteome. We also provide evidence for the
      existence of a network-like system for PABPs and their potential roles as
      critical hubs in intracellular behavior. This investigation takes a first step
      toward achieving a better understanding of the nature of polyanion-protein
      interactions within cells and introduces an alternative way of thinking about
      intracellular organization.

PMID- 16982675
TI  - WITHDRAWN: Parallel analysis of v-SRC mutant protein function using reverse
      transfection cell arrays.
AB  - This paper was withdrawn by the Publisher due to Publisher Error.

PMID- 16982677
TI  - Mice mutant in the DM domain gene Dmrt4 are viable and fertile but have
      polyovular follicles.
AB  - Proteins containing the DM domain, a zinc finger-like DNA binding motif, have
      been implicated in sexual differentiation in diverse metazoan organisms. Of seven
      mammalian DM domain genes, only Dmrt1 and Dmrt2 have been functionally analyzed.
      Here, we report expression analysis and targeted disruption of Dmrt4 (also called
      DmrtA1) in the mouse. Dmrt4 is widely expressed during embryonic and postnatal
      development. However, we find that mice homozygous for a putative null mutation
      in Dmrt4 develop essentially normally, undergo full sexual differentiation in
      both sexes, and are fertile. We observed two potential mutant phenotypes in Dmrt4
      mutant mice. First, ovaries of most mutant females have polyovular follicles,
      suggesting a role in folliculogenesis. Second, 25% of mutant males consistently
      exhibited copulatory behavior toward other males. We also tested potential
      redundancy between Dmrt4 and two other gonadally expressed DM domain genes, Dmrt1
      and Dmrt7. We observed no enhancement of gonadal phenotypes in the double
      mutants, suggesting that these genes function independently in gonadal
      development.

PMID- 16982676
TI  - Homeodomain transcription factor Phox2a, via cyclic AMP-mediated activation,
      induces p27Kip1 transcription, coordinating neural progenitor cell cycle exit and
      differentiation.
AB  - Mechanisms coordinating neural progenitor cell cycle exit and differentiation are
      incompletely understood. The cyclin-dependent kinase inhibitor p27(Kip1) is
      transcriptionally induced, switching specific neural progenitors from
      proliferation to differentiation. However, neuronal differentiation-specific
      transcription factors mediating p27(Kip1) transcription have not been identified.
      We demonstrate the homeodomain transcription factor Phox2a, required for central
      nervous system (CNS)- and neural crest (NC)-derived noradrenergic neuron
      differentiation, coordinates cell cycle exit and differentiation by inducing
      p27(Kip1) transcription. Phox2a transcription and activation in the CNS-derived
      CAD cell line and primary NC cells is mediated by combined cyclic AMP (cAMP) and
      bone morphogenetic protein 2 (BMP2) signaling. In the CAD cellular model, cAMP
      and BMP2 signaling initially induces proliferation of the undifferentiated
      precursors, followed by p27(Kip1) transcription, G(1) arrest, and neuronal
      differentiation. Small interfering RNA silencing of either Phox2a or p27(Kip1)
      suppresses p27(Kip1) transcription and neuronal differentiation, suggesting a
      causal link between p27(Kip1) expression and differentiation. Conversely, ectopic
      Phox2a expression via the Tet-off expression system promotes accelerated CAD cell
      neuronal differentiation and p27(Kip1) transcription only in the presence of cAMP
      signaling. Importantly, endogenous or ectopically expressed Phox2a activated by
      cAMP signaling binds homeodomain cis-acting elements of the p27(Kip1) promoter in
      vivo and mediates p27(Kip1)-luciferase expression in CAD and NC cells. We
      conclude that developmental cues of cAMP signaling causally link Phox2a
      activation with p27(Kip1) transcription, thereby coordinating neural progenitor
      cell cycle exit and differentiation.

PMID- 16982678
TI  - Polysome-bound endonuclease PMR1 is targeted to stress granules via stress
      specific binding to TIA-1.
AB  - The generalized process of mRNA decay involves deadenylation followed by release
      from translating polysomes, decapping, and exonuclease decay of the mRNA body. In
      contrast the mRNA endonuclease PMR1 forms a selective complex with its
      translating substrate mRNA, where it initiates decay by cleaving within the mRNA
      body. In stressed cells the phosphorylation of the alpha subunit of eukaryotic
      initiation factor 2 causes translating mRNAs to accumulate with stalled 48S
      subunits in large subcellular structures termed stress granules (SGs), wherein
      mRNAs undergo sorting for reinitiation, storage, or decay. Given the unique
      relationship between translation and PMR1-mediated mRNA decay, we examined the
      impact of stress-induced dissociation of polysomes on this process. Arsenite
      stress disrupts the polysome binding of PMR1 and its substrate mRNA but has no
      impact on the critical tyrosine phosphorylation of PMR1, its association with
      substrate mRNA, or its association with the functional approximately 680-kDa mRNP
      complex in which it normally resides on polysomes. We show that arsenite stress
      drives PMR1 into an RNase-resistant complex with TIA-1, and we identify a
      distinct domain in the N terminus of PMR1 that facilitates its interaction with
      TIA-1. Finally, we show that arsenite promotes the delayed association of PMR1
      with SGs under conditions which cause tristetraprolin and butyrate response
      factor 1, proteins that facilitate exonucleolytic mRNA, to exit SGs.

PMID- 16982679
TI  - MDM2 is required for suppression of apoptosis by activated Akt1 in salivary
      acinar cells.
AB  - Chronic damage to the salivary glands is a common side effect following head and
      neck irradiation. It is hypothesized that irreversible damage to the salivary
      glands occurs immediately after radiation; however, previous studies with rat
      models have not shown a causal role for apoptosis in radiation-induced injury. We
      report that etoposide and gamma irradiation induce apoptosis of salivary acinar
      cells from FVB control mice in vitro and in vivo; however, apoptosis is reduced
      in transgenic mice expressing a constitutively activated mutant of Akt1 (myr
      Akt1). Expression of myr-Akt1 in the salivary glands results in a significant
      reduction in phosphorylation of p53 at serine(18), total p53 protein
      accumulation, and p21(WAF1) or Bax mRNA following etoposide or gamma irradiation
      of primary salivary acinar cells. The reduced level of p53 protein in myr-Akt1
      salivary glands corresponds with an increase in MDM2 phosphorylation in vivo,
      suggesting that the Akt/MDM2/p53 pathway is responsible for suppression of
      apoptosis. Dominant-negative Akt blocked phosphorylation of MDM2 in salivary
      acinar cells from myr-Akt1 transgenic mice. Reduction of MDM2 levels in myr-Akt1
      primary salivary acinar cells with small interfering RNA increases the levels of
      p53 protein and renders these cells susceptible to etoposide-induced apoptosis in
      spite of the presence of activated Akt1. These results indicate that MDM2 is a
      critical substrate of activated Akt1 in the suppression of p53-dependent
      apoptosis in vivo.

PMID- 16982680
TI  - Binding of AlF-C, an Orc1-binding transcriptional regulator, enhances replicator
      activity of the rat aldolase B origin.
AB  - A region encompassing the rat aldolase B gene (aldB) promoter acts as a
      chromosomal origin of DNA replication (origin) in rat aldolase B-nonexpressing
      hepatoma cells. To examine replicator function of the aldB origin, we constructed
      recombinant mouse cell lines in which the rat aldB origin and the mutant
      derivatives were inserted into the same position at the mouse chromosome 8 by cre
      mediated recombination. Nascent strand abundance assays revealed that the rat
      origin acts as a replicator at the ectopic mouse locus. Mutation of site C in the
      rat origin, which binds an Orc1-binding protein AlF-C in vitro, resulted in a
      significant reduction of the replicator activity in the mouse cells. Chromatin
      immunoprecipitation (ChIP) assays indicated that the reduction of replicator
      activity was paralleled with the reduced binding of AlF-C and Orc1, suggesting
      that sequence-specific binding of AlF-C to the ectopic rat origin leads to
      enhanced replicator activity in cooperation with Orc1. Involvement of AlF-C in
      replication in vivo was further examined for the aldB origin at its original rat
      locus and for a different rat origin identified in the present study, which
      contained an AlF-C-binding site. ChIP assays revealed that both replication
      origins bind AlF-C and Orc1. We think that the results presented here may
      represent one mode of origin recognition in mammalian cells.

PMID- 16982681
TI  - The polypyrimidine tract binding protein (PTB) represses splicing of exon 6B from
      the beta-tropomyosin pre-mRNA by directly interfering with the binding of the
      U2AF65 subunit.
AB  - Splicing of exon 6B from the beta-tropomyosin pre-mRNA is repressed in nonmuscle
      cells and myoblasts by a complex array of intronic elements surrounding the exon.
      In this study, we analyzed the proteins that mediate splicing repression of exon
      6B through binding to the upstream element. We identified the polypyrimidine
      tract binding protein (PTB) as a component of complexes isolated from myoblasts
      that assemble onto the branch point region and the pyrimidine tract. In vitro
      splicing assays and PTB knockdown experiments by RNA interference demonstrated
      that PTB acts as a repressor of splicing of exon 6B. Using psoralen experiments,
      we showed that PTB acts at an early stage of spliceosome assembly by preventing
      the binding of U2 snRNA on the branch point. Using UV cross-linking and
      immunoprecipitation experiments with site-specific labeled RNA in PTB-depleted
      nuclear extracts, we found that the decrease in PTB was correlated with an
      increase in U2AF65. In addition, competition experiments showed that PTB is able
      to displace the binding of U2AF65 on the polypyrimidine tract. Our results
      strongly support a model whereby PTB competes with U2AF65 for binding to the
      polypyrimidine tract.

PMID- 16982682
TI  - Glucocorticoids regulate tristetraprolin synthesis and posttranscriptionally
      regulate tumor necrosis factor alpha inflammatory signaling.
AB  - Glucocorticoids are used to treat various inflammatory disorders, but the
      mechanisms underlying these actions are incompletely understood. The zinc finger
      protein tristetraprolin (TTP) destabilizes several proinflammatory cytokine mRNAs
      by binding to AU-rich elements within their 3' untranslated regions, targeting
      them for degradation. Here we report that glucocorticoids induce the synthesis of
      TTP mRNA and protein in A549 lung epithelial cells and in rat tissues.
      Dexamethasone treatment leads to a sustained induction of TTP mRNA expression
      that is abrogated by RU486. Glucocorticoid induction of TTP mRNA is also blocked
      by actinomycin D but not by cycloheximide, suggesting a transcriptional mechanism
      which has been confirmed by transcription run-on experiments. The most widely
      characterized TTP-regulated gene is the AU-rich tumor necrosis factor alpha (TNF
      alpha) gene. Dexamethasone represses TNF-alpha mRNA in A549 cells and decreases
      luciferase expression of a TNF-alpha 3' untranslated region reporter plasmid in
      an orientation-dependent manner. Small interfering RNAs to TTP significantly
      prevent this effect, and a cell line stably expressing a short-hairpin RNA to TTP
      conclusively establishes that TTP is critical for dexamethasone inhibition of TNF
      alpha mRNA expression. These studies provide the molecular evidence for
      glucocorticoid regulation of human TTP and reflect a novel inductive anti
      inflammatory signaling pathway for glucocorticoids that acts via
      posttranscriptional mechanisms.

PMID- 16982683
TI  - ShcA mediates the dominant pathway to extracellular signal-regulated kinase
      activation during early thymic development.
AB  - During thymic development, the beta selection checkpoint is regulated by pre-T
      cell receptor-initiated signals. Progression through this checkpoint is
      influenced by phosphorylation and activation of the serine/threonine kinases
      extracellular signal-regulated kinase 1 (ERK1) and ERK2, but the in vivo
      relevance of specific upstream players leading to ERK activation is not known.
      Here, using mice with a conditional loss of the shc1 gene or expressing mutants
      of ShcA, we demonstrate that the adapter protein ShcA is responsible for up to
      70% of ERK activation in double-negative (DN) thymocytes in vivo and ex vivo. We
      also identify two specific tyrosines on ShcA that promote ERK phosphorylation in
      vivo, and mice expressing ShcA with mutations of these tyrosines show impaired DN
      thymocyte development. This work provides the first in vivo demonstration of the
      relative requirement of upstream adapters in controlling ERK activation during
      beta selection and suggests a dominant role for ShcA.

PMID- 16982684
TI  - Role of the cyclic AMP response element in the bcl-2 promoter in the regulation
      of endogenous Bcl-2 expression and apoptosis in murine B cells.
AB  - We have previously shown for B-cell lines that the cyclic AMP response element
      (CRE) is a major positive regulatory site in the bcl-2 promoter. However, the
      role of the CRE in the regulation of endogenous bcl-2 expression in vivo has not
      been characterized. We used gene targeting to generate knock-in mice in which a
      mutated CRE was introduced into the bcl-2 promoter region (mutCRE-bcl2 mice).
      Quantitative chromatin immunoprecipitation assays revealed that mutation of the
      CRE abolished the binding of CREB/ATF and CBP transcription factors to the bcl-2
      promoter and greatly diminished the binding of NF-kappaB factors. The mutant CRE
      significantly reduced the expression of Bcl-2 in B cells and rendered them
      susceptible to surface immunoglobulin- and chemotherapeutic agent-induced
      apoptosis. The low levels of Bcl-2 were not changed with activation of the cells.
      The numbers of pre-B, immature B, and mature B cells in the bone marrow were
      decreased, as were the numbers of splenic B cells in mutCRE-bcl2 mice. Our
      findings indicate that the CRE in the bcl-2 promoter has an important functional
      role in the regulation of endogenous Bcl-2 expression and plays a critical role
      in the coordination of signals that regulate B-cell survival.

PMID- 16982685
TI  - Ubiquitin-binding motifs in REV1 protein are required for its role in the
      tolerance of DNA damage.
AB  - REV1 protein is a eukaryotic member of the Y family of DNA polymerases involved
      in the tolerance of DNA damage by replicative bypass. The precise role(s) of REV1
      in this process is not known. Here we show, by using the yeast two-hybrid assay
      and the glutathione S-transferase pull-down assay, that mouse REV1 can physically
      interact with ubiquitin. The association of REV1 with ubiquitin requires the
      ubiquitin-binding motifs (UBMs) located at the C terminus of REV1. The UBMs also
      mediate the enhanced association between monoubiquitylated PCNA and REV1. In
      cells exposed to UV radiation, the association of REV1 with replication foci is
      dependent on functional UBMs. The UBMs of REV1 are shown to contribute to DNA
      damage tolerance and damage-induced mutagenesis in vivo.

PMID- 16982686
TI  - Serotonin increases phosphorylation of synaptic 4EBP through TOR, but eukaryotic
      initiation factor 4E levels do not limit somatic cap-dependent translation in
      aplysia neurons.
AB  - The target of rapamycin (TOR) plays an important role in memory formation in
      Aplysia californica. Here, we characterize one of the downstream targets of TOR,
      the eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP) from Aplysia.
      Aplysia 4EBP contains the four critical phosphorylation sites regulated by TOR as
      well as an N-terminal RAIP motif and a C-terminal TOS site. Aplysia 4EBP was
      hypophosphorylated in synaptosomes, and serotonin addition caused a rapamycin
      sensitive increase in 4EBP phosphorylation both in synaptosomes and in isolated
      neurites. Aplysia 4EBP was regulated in a fashion similar to that of mammalian
      4EBPs, binding to eIF4E when dephosphorylated and releasing eIF4E after
      phosphorylation. Overexpression of 4EBP in the soma of Aplysia neurons caused a
      specific decrease in cap-dependent translation that was rescued by concomitant
      overexpression of eIF4E. However, eIF4E overexpression by itself did not increase
      cap-dependent translation, suggesting that increasing levels of free eIF4E by
      phosphorylating 4EBP is not important in regulating cap-dependent translation in
      the cell soma. Total levels of eIF4E were also regulated by 4EBP, suggesting that
      4EBP can also act as an eIF4E chaperone. These studies demonstrate the conserved
      nature of 4EBP regulation and its role in cap-dependent translation and suggest
      differential roles of 4EBP phosphorylation in the soma and synapse.

PMID- 16982687
TI  - Two domains of the erythropoietin receptor are sufficient for Jak2
      binding/activation and function.
AB  - Biochemical and genetic studies have shown that Jak2 is an essential component of
      EpoR signal transduction which is required for normal erythropoiesis. However,
      whether Jak2 is the sole direct mediator of EpoR signal transduction remains
      controversial. To address this issue, we have used an extensive and systematic
      mutational analysis across the EpoR cytoplasmic tail and transmembrane domain
      with the goal of determining whether mutants that negatively affected EpoR
      biological activity but retained Jak2 activation could be identified. Analysis of
      over 40 mutant receptors established that two large domains in the membrane
      proximal region, which include the previously defined Box1 and Box2 domains as
      well as a highly conserved glycine among cytokine receptors, are required for
      Jak2 binding and activation and to sustain biological activity of the receptor.
      Importantly, none of the mutants that lost the ability to activate Jak2 retained
      the ability to bind Jak2, thus questioning the validity of models of receptor
      reorientation for Jak2 activation. Also, no correlation was made between cell
      surface expression of the receptor and its ability to bind Jak2, thus questioning
      the role of Jak2 in trafficking the receptor to the plasma membrane.
      Collectively, the results suggest that Jak2 is the sole direct signaling molecule
      downstream of EpoR required for biological activity.

PMID- 16982688
TI  - Role of RNA polymerase III transcription factors in the selection of integration
      sites by the dictyostelium non-long terminal repeat retrotransposon TRE5-A.
AB  - In the compact Dictyostelium discoideum genome, non-long terminal repeat (non
      LTR) retrotransposons known as TREs avoid accidental integration-mediated gene
      disruption by targeting the vicinity of tRNA genes. In this study we provide the
      first evidence that proteins of a non-LTR retrotransposon interact with a target
      specific transcription factor to direct its integration. We applied an in vivo
      selection system that allows for the isolation of natural TRE5-A integrations
      into a known genomic location upstream of tRNA genes. TRE5-A frequently modified
      the integration site in a way characteristic of other non-LTR retrotransposons by
      adding nontemplated extra nucleotides and generating small and extended target
      site deletions. Mutations within the B-box promoter of the targeted tRNA genes
      interfered with both the in vitro binding of RNA polymerase III transcription
      factor TFIIIC and the ability of TRE5-A to target these genes. An isolated B box
      was sufficient to enhance TRE5-A integration in the absence of a surrounding tRNA
      gene. The RNA polymerase III-transcribed ribosomal 5S gene recruits TFIIIC in a B
      box-independent manner, yet it was readily targeted by TRE5-A in our assay. These
      results suggest a direct role of an RNA polymerase III transcription factor in
      the targeting process.

PMID- 16982689
TI  - Activation of Saccharomyces cerevisiae HIS3 results in Gcn4p-dependent, SWI/SNF
      dependent mobilization of nucleosomes over the entire gene.
AB  - The effects of transcriptional activation on the chromatin structure of the
      Saccharomyces cerevisiae HIS3 gene were addressed by mapping the precise
      positions of nucleosomes in uninduced and induced chromatin. In the absence of
      the Gcn4p activator, the HIS3 gene is organized into a predominant nucleosomal
      array. In wild-type chromatin, this array is disrupted, and several alternative
      overlapping nucleosomal arrays are formed. The disruption of the predominant
      array also requires the SWI/SNF remodeling machine, indicating that the SWI/SNF
      complex plays an important role in nucleosome mobilization over the entire HIS3
      gene. The Isw1 remodeling complex plays a more subtle role in determining
      nucleosome positions on HIS3, favoring positions different from those preferred
      by the SWI/SNF complex. Both the SWI/SNF and Isw1 complexes are constitutively
      present in HIS3 chromatin, although Isw1 tends to be excluded from the HIS3
      promoter. Despite the apparent disorder of HIS3 chromatin generated by the
      formation of multiple nucleosomal arrays, nucleosome density profiles indicate
      that some long-range order is always present. We propose that Gcn4p stimulates
      nucleosome mobilization over the entire HIS3 gene by the SWI/SNF complex. We
      suggest that the net effect of interplay among remodeling machines at HIS3 is to
      create a highly dynamic chromatin structure.

PMID- 16982690
TI  - Tyk2 tyrosine kinase expression is required for the maintenance of mitochondrial
      respiration in primary pro-B lymphocytes.
AB  - Tyk2, a member of the Jak family of protein tyrosine kinases, is critical for the
      biological actions of alpha/beta interferon (IFN-alpha/beta). Although Tyk2(-/-)
      mice are phenotypically normal, they exhibit abnormal responses to inflammatory
      challenges in a variety of cells isolated from Tyk2(-/-) mice. The reported
      phenotypic alterations in both Tyk2-null cells and mice are consistent with the
      possibility that the expression of this tyrosine kinase may regulate
      mitochondrial function. We report here that Tyk2-null pro-B cells are markedly
      deficient in basal oxygen consumption and exhibit a significant decrease in
      steady-state cellular ATP levels compared to wild-type cells. Tyk2-null cells
      also exhibit impaired complex I, III, and IV function of the mitochondrial
      electron transport chain. Reconstitution of Tyk2-null pro-B cells with either the
      wild type or a kinase-inactive mutant of Tyk2 restores basal mitochondrial
      respiration. By contrast, the kinase activity of Tyk2 is required for maintenance
      of both complex I-dependent mitochondrial respiration as well as induction of
      apoptosis in cells incubated with IFN-beta. Consistent with the role of Tyk2 in
      the regulation of tyrosine phosphorylation of Stat3, expression of a
      constitutively active Stat3 can restore the mitochondrial respiration in Tyk2
      null cells treated with IFN-beta. Finally, Tyk2(-/-) mice show decreased exercise
      tolerance compared to wild-type littermates. Our results implicate a novel role
      for Tyk2 kinase and Stat3 phosphorylation in mitochondrial respiration.

PMID- 16982691
TI  - Regulation of the M-cadherin-beta-catenin complex by calpain 3 during terminal
      stages of myogenic differentiation.
AB  - The cysteine protease calpain 3 (CAPN3) is essential for normal muscle function,
      since mutations in CAPN3 cause limb girdle muscular dystrophy type 2A.
      Previously, we showed that myoblasts isolated from CAPN3 knockout (C3KO) mice
      were able to fuse to myotubes; however, sarcomere formation was disrupted. In
      this study we further characterized morphological and biochemical features of
      C3KO myotubes in order to elucidate a role for CAPN3 during myogenesis. We showed
      that cell cycle withdrawal occurred normally in C3KO cultures, but C3KO myotubes
      have an increased number of myonuclei per myotube. We found that CAPN3 acts
      during myogenesis to specifically control levels of membrane-associated but not
      cytoplasmic beta-catenin and M-cadherin. CAPN3 was able to cleave both proteins,
      and in the absence of CAPN3, M-cadherin and beta-catenin abnormally accumulated
      at the membranes of myotubes. Given the role of M-cadherin in myoblast fusion,
      this finding suggests that the excessive myonuclear index of C3KO myotubes was
      due to enhanced fusion. Postfusion events, such as beta1D integrin expression and
      myofibrillogenesis, were suppressed in C3KO myotubes. These data suggest that the
      persistence of fusion observed in C3KO cells inhibits subsequent steps of
      differentiation, such as integrin complex rearrangements and sarcomere assembly.

PMID- 16982692
TI  - KLHL1/MRP2 mediates neurite outgrowth in a glycogen synthase kinase 3beta
      dependent manner.
AB  - The actin-based cytoskeleton is essential for the generation and maintenance of
      cell polarity, cellular motility, and the formation of neural cell processes.
      MRP2 is an actin-binding protein of the kelch-related protein family. While MRP2
      has been shown to be expressed specifically in brain, its function is still
      unknown. Here, we report that in neuronal growth factor (NGF)-induced PC12 cells,
      MRP2 was expressed along the neurite processes and colocalized with Talin at the
      growth cones. MRP2 mRNA and protein levels were up-regulated in PC12 cells
      following NGF stimulation. Moreover, treatment of PC12 cells with interfering
      RNAs for MRP2 and glycogen synthase kinase 3beta (GSK3beta) resulted in the
      inhibition of neurite outgrowth. A significant decrease in MRP2 expression levels
      was observed following GSK3beta inhibition, which was correlated with the
      inhibited neurite outgrowth, while GSK3beta overexpression was found to increase
      MRP2 expression levels. MRP2 interacted with GSK3beta through its NH2 terminus
      containing the BTB domain, and these molecules colocalized along neurite
      processes and growth cones in differentiated PC12 cells and rat primary
      hippocampal neurons. Additionally, increased associations of MRP2 with GSK3beta
      and MRP2 with actin were observed in the NGF-treated PC12 cells. Thus, this study
      provides, for the first time, insights into the involvement of MRP2 in neurite
      outgrowth, which occurs in a GSK3beta-dependent manner.

PMID- 16982693
TI  - Specific isoforms of translation initiation factor 4GI show differences in
      translational activity.
AB  - The eukaryotic initiation factor (eIF) 4GI gene locus (eIF4GI) contains three
      identified promoters, generating alternately spliced mRNAs, yielding a total of
      five eIF4GI protein isoforms. Although eIF4GI plays a critical role in mRNA
      recruitment to the ribosomes, little is known about the functions of the
      different isoforms, their partner binding capacities, or the role of the homolog,
      eIF4GII, in translation initiation. To directly address this, we have used short
      interfering RNAs (siRNAs) expressed from DNA vectors to silence the expression of
      eIF4GI in HeLa cells. Here we show that reduced levels of specific mRNA and
      eIF4GI isoforms in HeLa cells promoted aberrant morphology and a partial
      inhibition of translation. The latter reflected dephosphorylation of 4E-BP1 and
      decreased eIF4F complex levels, with no change in eIF2alpha phosphorylation.
      Expression of siRNA-resistant Myc-tagged eIF4GI isoforms has allowed us to show
      that the different isoforms exhibit significant differences in their ability to
      restore translation rates. Here we quantify the efficiency of eIF4GI promoter
      usage in mammalian cells and demonstrate that even though the longest isoform of
      eIF4GI (eIF4GIf) was relatively poorly expressed when reintroduced, it was more
      efficient at promoting the translation of cellular mRNAs than the more highly
      expressed shorter isoforms used in previous functional studies.

PMID- 16982694
TI  - The middle domain of Hsp90 acts as a discriminator between different types of
      client proteins.
AB  - The mechanism of client protein activation by Hsp90 is enigmatic, and it is
      uncertain whether Hsp90 employs a common route for all proteins. Using a
      mutational analysis approach, we investigated the activation of two types of
      client proteins, glucocorticoid receptor (GR) and the kinase v-Src by the middle
      domain of Hsp90 (Hsp90M) in vivo. Remarkably, the overall cellular activity of v
      Src was highly elevated in a W300A mutant yeast strain due to a 10-fold increase
      in cellular protein levels of the kinase. In contrast, the cellular activity of
      GR remained almost unaffected by the W300A mutation but was dramatically
      sensitive to S485Y and T525I exchanges. In addition, we show that mutations S485Y
      and T525I in Hsp90M reduce the ATP hydrolysis rate, suggesting that Hsp90 ATPase
      is more tightly regulated than assumed previously. Therefore, the activation of
      GR and v-Src has various demands on Hsp90 biochemistry and is dependent on
      separate functional regions of Hsp90M. Thus, Hsp90M seems to discriminate between
      different substrate types and to adjust the molecular chaperone for proper
      substrate activation.

PMID- 16982695
TI  - Prostaglandin E2 induces fibroblast growth factor 9 via EP3-dependent protein
      kinase Cdelta and Elk-1 signaling.
AB  - Fibroblast growth factor 9 (FGF-9) is a potent mitogen that controls the proper
      development of many tissues and organs. In contrast, aberrant expression of FGF-9
      also results in the evolution of many human diseases, such as cancers and
      endometriosis. Despite its vital function being reported, the cellular and
      molecular mechanisms responsible for the regulation of FGF-9 expression are
      mostly unknown. We report here that prostaglandin E2 (PGE2) induces expression of
      FGF-9, which promotes endometriotic stromal cell proliferation, through the EP3
      receptor-activated protein kinase Cdelta (PKCdelta) signaling pathway. Activation
      of PKCdelta leads to phosphorylation of ERK1/2, and the transcription factor Elk
      1 thereby promotes transcription of FGF-9. Two Elk-1 cis-binding sites located at
      nucleotides -1324 to -1329 and -1046 to -1051 of the human FGF-9 promoter are
      identified as crucial for mediating PGE2 actions. Collectively, we demonstrate,
      for the first time, that PGE2 can directly induce FGF-9 expression via a novel
      signaling pathway involving EP3, PKCdelta, and a member of the ETS domain
      containing transcription factor superfamily in primary human endometriotic
      stromal cells. Our findings may also provide a molecular framework for
      considering roles for PGE2 in FGF-9-related embryonic development and/or human
      diseases.

PMID- 16982696
TI  - Serum- and glucocorticoid-inducible kinase 1 (SGK1) increases neurite formation
      through microtubule depolymerization by SGK1 and by SGK1 phosphorylation of tau.
AB  - Serum- and glucocorticoid-inducible kinase 1 (SGK1) is a member of the Ser/Thr
      protein kinase family that regulates a variety of cell functions. Recently, SGK1
      was shown to increase dendritic growth but the mechanism underlying the increase
      is unknown. Here we demonstrated that SGK1 increased the neurite formation of
      cultured hippocampal neurons through microtubule (MT) depolymerization via two
      distinct mechanisms. First, SGK1 directly depolymerized MTs. In vitro MT
      depolymerization experiments revealed that SGK1, especially N-truncated SGK1,
      directly disassembled self-polymerized MTs and taxol-stabilized MTs in a dose
      dependent and ATP-independent manner. The transfection of sgk1 to HeLa cells also
      inhibited MT assembly in vivo. Second, SGK1 indirectly depolymerized MTs through
      the phosphorylation of tau at Ser214. An in vitro kinase assay revealed that
      active SGK1 phosphorylated tau Ser214 specifically. In vivo transfection of sgk1
      also phosphorylated tau Ser214 in HEK293T cells and hippocampal neurons. Further,
      sgk1 transfection significantly increased the number of primary neurites and
      shortened the length of the total process in cultured hippocampal neurons. These
      effects were antagonized by the cotransfection of the tauS214A mutant plasmid.
      Dexamethasone, a synthetic glucocorticoid, mimics the effect of sgk1
      overexpression. Together, these results suggest that SGK1 enhances neurite
      formation through MT depolymerization by a direct action of SGK1 and by the SGK1
      phosphorylation of tau.

PMID- 16982697
TI  - A CTX family cell adhesion molecule, JAM4, is expressed in stem cell and
      progenitor cell populations of both male germ cell and hematopoietic cell
      lineages.
AB  - Stem cells are maintained in an undifferentiated state by interacting with a
      microenvironment known as the "niche," which is comprised of various secreted and
      membrane proteins. Our goal was to identify niche molecules participating in stem
      cell-stem cell and/or stem cell-supporting cell interactions. Here, we isolated
      genes encoding secreted and membrane proteins from purified male germ stem cells
      using a signal sequence trap approach. Among the genes identified, we focused on
      the junctional adhesion molecule 4 (JAM4), an immunoglobulin type cell adhesion
      molecule. JAM4 protein was actually localized to the plasma membrane in male germ
      cells. JAM4 expression was downregulated as cells differentiated in both germ
      cell and hematopoietic cell lineages. To analyze function in vivo, we generated
      JAM4-deficient mice. Histological analysis of testes from homozygous nulls did
      not show obvious abnormalities, nor did liver and kidney tissues, both of which
      strongly express JAM4. The numbers of hematopoietic stem cells in bone marrow
      were indistinguishable between wild-type and mutant mice, as was male germ cell
      development. These results suggest that JAM4 is expressed in stem cells and
      progenitor cells but that other cell adhesion molecules may substitute for JAM4
      function in JAM4-deficient mice both in male germ cell and hematopoietic
      lineages.

PMID- 16982698
TI  - CIB1 is essential for mouse spermatogenesis.
AB  - CIB1 is a 22-kDa calcium binding, regulatory protein with approximately 50%
      homology to calmodulin and calcineurin B. CIB1 is widely expressed and binds to a
      number of effectors, such as integrin alphaIIb, PAK1, and polo-like kinases, in
      different tissues. However, the in vivo functions of CIB1 are not well
      understood. To elucidate the function of CIB1 in whole animals, we used
      homologous recombination in embryonic stem cells to generate Cib1(-/-) mice.
      Although Cib1(-/-) mice grow normally, the males are sterile due to disruption of
      the haploid phase of spermatogenesis. This is associated with reduced testis size
      and numbers of germ cells in seminiferous tubules, increased germ cell apoptosis,
      and the loss of elongated spermatids and sperm. Cib1(-/-) testes also show
      increased mRNA and protein expression of the cell cycle regulator Cdc2/Cdk1. In
      addition, mouse embryonic fibroblasts (MEFs) derived from Cib1(-/-) mice exhibit
      a much slower growth rate compared to Cib1(+/+) MEFs, suggesting that CIB1
      regulates the cell cycle, differentiation of spermatogenic germ cells, and/or
      differentiation of supporting Sertoli cells.

PMID- 16982699
TI  - Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit
      through p21 binding.
AB  - Protein kinase B (PKB/Akt) is an important modulator of insulin signaling, cell
      proliferation, and survival. Using small interfering RNA duplexes in
      nontransformed mammalian cells, we show that only Akt1 is essential for cell
      proliferation, while Akt2 promotes cell cycle exit. Silencing Akt1 resulted in
      decreased cyclin A levels and inhibition of S-phase entry, effects not seen with
      Akt2 knockdown and specifically rescued by microinjection of Akt1, not Akt2. In
      differentiating myoblasts, Akt2 knockout prevented myoblasts from exiting the
      cell cycle and showed sustained cyclin A expression. In contrast, overexpression
      of Akt2 reduced cyclin A and hindered cell cycle progression in M-G1 with
      increased nuclear p21. p21 is a major target in the differential effects of Akt
      isoforms, with endogenous Akt2 and not Akt1 binding p21 in the nucleus and
      increasing its level. Accordingly, Akt2 knockdown cells, and not Akt1 knockdown
      cells, showed reduced levels of p21. A specific Akt2/p21 interaction can be
      reproduced in vitro, and the Akt2 binding site on p21 is similar to that in
      cyclin A spanning T145 to T155, since (i) prior incubation with cyclin A prevents
      Akt2 binding, (ii) T145 phosphorylation on p21 by Akt1 prevents Akt2 binding, and
      (iii) binding Akt2 prevents phosphorylation of p21 by Akt1. These data show that
      specific interaction of the Akt2 isoform with p21 is key to its negative effect
      on normal cell cycle progression.

PMID- 16982702
TI  - A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino) methyl]amino}-2,2
      dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a novel and selective P2X7
      receptor antagonist, dose-dependently reduces neuropathic pain in the rat.
AB  - ATP-sensitive P2X(7) receptors are localized on cells of immunological origin
      including glial cells in the central nervous system. Activation of P2X(7)
      receptors leads to rapid changes in intracellular calcium concentrations, release
      of the proinflammatory cytokine interleukin-1beta (IL-1beta), and following
      prolonged agonist exposure, cytolytic plasma membrane pore formation. P2X(7)
      knockout mice show reduced inflammation as well as decreased nociceptive
      sensitivity following peripheral nerve injury. A-740003 (N-(1-{[(cyanoimino)(5
      quinolinylamino) methyl] amino}-2,2-dimethylpropyl)-2-(3,4
      dimethoxyphenyl)acetamide) is a novel competitive antagonist of P2X(7) receptors
      (IC(50) values = 40 nM for human and 18 nM for rat) as measured by agonist
      stimulated changes in intracellular calcium concentrations. A-740003 showed weak
      or no activity (IC(50) > 10 muM) at other P2 receptors and an array of other
      neurotransmitter and peptide receptors, ion channels, reuptake sites, and
      enzymes. A-740003 potently blocked agonist-evoked IL-1beta release (IC(50) = 156
      nM) and pore formation (IC(50) = 92 nM) in differentiated human THP-1 cells.
      Systemic administration of A-740003 produced dose-dependent antinociception in a
      spinal nerve ligation model (ED(50) = 19 mg/kg i.p.) in the rat. A-740003 also
      attenuated tactile allodynia in two other models of neuropathic pain, chronic
      constriction injury of the sciatic nerve and vincristine-induced neuropathy. In
      addition, A-740003 effectively reduced thermal hyperalgesia observed following
      intraplantar administration of carrageenan or complete Freund's adjuvant (ED(50)
      = 38-54 mg/kg i.p.). A-740003 was ineffective in attenuating acute thermal
      nociception in normal rats and did not alter motor performance at analgesic
      doses. These data demonstrate that selective blockade of P2X(7) receptors in vivo
      produces significant antinociception in animal models of neuropathic and
      inflammatory pain.

PMID- 16982700
TI  - Screening for PTB domain binding partners and ligand specificity using proteome
      derived NPXY peptide arrays.
AB  - Modular interaction domains that recognize peptide motifs in target proteins can
      impart selectivity in signaling pathways. Phosphotyrosine binding (PTB) domains
      are components of cytoplasmic docking proteins that bind cell surface receptors
      through NPXY motifs. We have employed a library of human proteome-derived NXXY
      sequences to explore PTB domain specificity and function. SPOTS peptide arrays
      were used to create a comprehensive matrix of receptor motifs that were probed
      with a set of 10 diverse PTB domains. This approach confirmed that individual PTB
      domains have selective and distinct recognition properties and provided a means
      to explore over 2,500 potential PTB domain-NXXY interactions. The results
      correlated well with previously known associations between full-length proteins
      and predicted novel interactions, as well as consensus binding data for specific
      PTB domains. Using the Ret, MuSK, and ErbB2 receptor tyrosine kinases, we show
      that interactions of these receptors with PTB domains predicted to bind by the
      NXXY arrays do occur in cells. Proteome-based peptide arrays can therefore
      identify networks of receptor interactions with scaffold proteins that may be
      physiologically relevant.

PMID- 16982701
TI  - Transcriptional coactivator PC4, a chromatin-associated protein, induces
      chromatin condensation.
AB  - Human transcriptional coactivator PC4 is a highly abundant multifunctional
      protein which plays diverse important roles in cellular processes, including
      transcription, replication, and repair. It is also a unique activator of p53
      function. Here we report that PC4 is a bona fide component of chromatin with
      distinct chromatin organization ability. PC4 is predominantly associated with the
      chromatin throughout the stages of cell cycle and is broadly distributed on the
      mitotic chromosome arms in a punctate manner except for the centromere. It
      selectively interacts with core histones H3 and H2B; this interaction is
      essential for PC4-mediated chromatin condensation, as demonstrated by micrococcal
      nuclease (MNase) accessibility assays, circular dichroism spectroscopy, and
      atomic force microscopy (AFM). The AFM images show that PC4 compacts the 100-kb
      reconstituted chromatin distinctly compared to the results seen with the linker
      histone H1. Silencing of PC4 expression in HeLa cells results in chromatin
      decompaction, as evidenced by the increase in MNase accessibility. Knocking down
      of PC4 up-regulates several genes, leading to the G2/M checkpoint arrest of cell
      cycle, which suggests its physiological role as a chromatin-compacting protein.
      These results establish PC4 as a new member of chromatin-associated protein
      family, which plays an important role in chromatin organization.

PMID- 16982703
TI  - Pifithrin-alpha enhances chemosensitivity by a p38 mitogen-activated protein
      kinase-dependent modulation of the eukaryotic initiation factor 4E in malignant
      cholangiocytes.
AB  - Pifithrin-alpha is the lead compound for a novel group of small molecules that
      are being developed for use as anticancer agents. The eukaryotic initiation
      factor 4E (eIF-4E) is overexpressed in many cancers, it can mediate sensitivity
      to therapy, and it may be regulated by p53. We examined the utility of pifithrin
      alpha as an adjunct to therapy for the treatment of human cholangiocarcinoma, a
      tumor that is highly refractory to therapy, and we assessed the involvement of
      p53-dependent eIF-4E regulation in cellular responses to pifithrin-alpha. The
      expression of eIF-4E was increased in human cholangiocarcinomas compared with
      normal liver. Modulation of eIF-4E expression by RNA interference enhanced the
      efficacy of gemcitabine in KMCH cholangiocarcinoma cells. Preincubation of KMCH
      cells with pifithrin-alpha enhanced gemcitabine-induced cytotoxicity in an eIF-4E
      dependent manner. Furthermore, pifithrin-alpha increased eIF-4E phosphorylation
      at serine 209 via activation of p38 mitogen-activated protein kinase (MAPK).
      Pifithrin-alpha was shown to activate aryl hydrocarbon receptor (AhR) signaling
      and p38 MAPK activation. Sequencing analysis indicated the presence of a
      functionally inactivating p53 mutation in KMCH cells, and small interfering RNA
      to p53 did not modulate chemosensitization by pifithrin-alpha. Pifithrin-alpha
      enhanced chemosensitivity by a mechanism independent of p53 and involving AhR and
      p38 MAPK deregulation of eIF-4E phosphorylation. Thus, pifithrin-alpha may prove
      useful for enhancing chemosensitivity in tumors with mutated p53. Moreover,
      modulation of eIF-4E is an attractive therapeutic target for intervention in
      cancer treatment.

PMID- 16982704
TI  - Acetylcholine release at neuromuscular junctions of adult tottering mice is
      controlled by N-(cav2.2) and R-type (cav2.3) but not L-type (cav1.2) Ca2+
      channels.
AB  - The mutation in the alpha(1A) subunit gene of the P/Q-type (Ca(v)2.1) Ca(2+)
      channel present in tottering (tg) mice causes ataxia and motor seizures that
      resemble absence epilepsy in humans. P/Q-type Ca(2+)channels are primarily
      involved in acetylcholine (ACh) release at mammalian neuromuscular junctions.
      Unmasking of L-type (Ca(v)1.1-1.2) Ca(2+) channels occurs in cerebellar Purkinje
      cells of tg mice. However, whether L-type Ca(2+) channels are also up-regulated
      at neuromuscular junctions of tg mice is unknown. We characterized thoroughly the
      pharmacological sensitivity of the Ca(2+) channels, which control ACh release at
      adult tg neuromuscular junctions. Block of N- and R-type (Ca(v)2.2-2.3), but not
      L-type Ca(2+) channels, significantly reduced quantal content of end-plate
      potentials in tg preparations. Neither resting nor KCl-evoked miniature end-plate
      potential frequency differed significantly between tg and wild type (WT).
      Immunolabeling of Ca(2+) channel subunits alpha(1A), alpha(1B), alpha(1C), and
      alpha(1E) revealed an apparent increase of alpha(1B), and alpha(1E) staining, at
      tg but not WT neuromuscular junctions. This presumably compensates for the
      deficit of P/Q-type Ca(2+)channels, which localized presynaptically at WT
      neuromuscular junctions. No alpha(1C) subunits juxtaposed with pre- or
      postsynaptic markers at either WT or tg neuromuscular junctions. Thus, in adult
      tg mice, immunocytochemical and electrophysiological data indicate that N- and R
      type channels both assume control of ACh release at motor nerve terminals.
      Recruitment of alternate subtypes of Ca(2+) channels to control transmitter
      release seems to represent a commonly occurring method of neuronal plasticity.
      However, it is unclear which conditions underlie recruitment of Ca(v)2 as opposed
      to Ca(v)1-type Ca(2+) channels.

PMID- 16982706
TI  - Clearcut: a fast implementation of relaxed neighbor joining.
AB  - SUMMARY: Clearcut is an open source implementation for the relaxed neighbor
      joining (RNJ) algorithm. While traditional neighbor joining (NJ) remains a
      popular method for distance-based phylogenetic tree reconstruction, it suffers
      from a O(N(3)) time complexity, where N represents the number of taxa in the
      input. Due to this steep asymptotic time complexity, NJ cannot reasonably handle
      very large datasets. In contrast, RNJ realizes a typical-case time complexity on
      the order of N(2)logN without any significant qualitative difference in output.
      RNJ is particularly useful when inferring a very large tree or a large number of
      trees. In addition, RNJ retains the desirable property that it will always
      reconstruct the true tree given a matrix of additive pairwise distances. Clearcut
      implements RNJ as a C program, which takes either a set of aligned sequences or a
      pre-computed distance matrix as input and produces a phylogenetic tree.
      Alternatively, Clearcut can reconstruct phylogenies using an extremely fast
      standard NJ implementation. AVAILABILITY: Clearcut source code is available for
      download at: http://bioinformatics.hungry.com/clearcut

PMID- 16982705
TI  - Identification and expression analysis of twelve members of the nucleobase
      ascorbate transporter (NAT) gene family in Arabidopsis thaliana.
AB  - By screening genome databases, 12 genes encoding membrane proteins homologous to
      nucleobase-ascorbate transporters (NATs) were identified in Arabidopsis thaliana.
      A similar number of genes was found in the rice genome. The plant NAT proteins
      split into five clades (I-V) based on protein multisequence alignments. This
      classification nicely correlates with the patterns of organ- and tissue-specific
      expression during the whole life cycle of A. thaliana. Interestingly, expression
      of two members of clade III, AtNAT7 and AtNAT8, was found to be up-regulated in
      undifferentiated tissues such as callus or tumors produced by Agrobacterium
      tumefaciens. Clade V comprises AtNAT12 possessing a hydrophilic N-terminal
      extension. Transient expression of green fluorescent protein (GFP) fusions in
      different systems showed that AtNAT12 along with AtNAT7 and -8 are located in the
      plasma membrane. Mutations in any of the AtNAT genes do not induce phenotypic
      alterations. The absence of obvious mutant phenotypes in single but also in
      double and triple mutants suggests a high degree of functional redundancy between
      AtNAT genes, but might also point to redundant functions provided by genes or
      pathways unrelated to the AtNATs.

PMID- 16982707
TI  - ADAM: another database of abbreviations in MEDLINE.
AB  - MOTIVATION: Abbreviations are an important type of terminology in the biomedical
      domain. Although several groups have already created databases of biomedical
      abbreviations, these are either not public, or are not comprehensive, or focus
      exclusively on acronym-type abbreviations. We have created another abbreviation
      database, ADAM, which covers commonly used abbreviations and their definitions
      (or long-forms) within MEDLINE titles and abstracts, including both acronym and
      non-acronym abbreviations. RESULTS: A model of recognizing abbreviations and
      their long-forms from titles and abstracts of MEDLINE (2006 baseline) was
      employed. After grouping morphological variants, 59 405 abbreviation/long-form
      pairs were identified. ADAM shows high precision (97.4%) and includes most of the
      frequently used abbreviations contained in the Unified Medical Language System
      (UMLS) Lexicon and the Stanford Abbreviation Database. Conversely, one-third of
      abbreviations in ADAM are novel insofar as they are not included in either
      database. About 19% of the novel abbreviations are non-acronym-type and these
      cover at least seven different types of short-form/long-form pairs. AVAILABILITY:
      A free, public query interface to ADAM is available at
      http://arrowsmith.psych.uic.edu, and the entire database can be downloaded as a
      text file.

PMID- 16982708
TI  - RankProd: a bioconductor package for detecting differentially expressed genes in
      meta-analysis.
AB  - While meta-analysis provides a powerful tool for analyzing microarray experiments
      by combining data from multiple studies, it presents unique computational
      challenges. The Bioconductor package RankProd provides a new and intuitive tool
      for this purpose in detecting differentially expressed genes under two
      experimental conditions. The package modifies and extends the rank product method
      proposed by Breitling et al., [(2004) FEBS Lett., 573, 83-92] to integrate
      multiple microarray studies from different laboratories and/or platforms. It
      offers several advantages over t-test based methods and accepts pre-processed
      expression datasets produced from a wide variety of platforms. The significance
      of the detection is assessed by a non-parametric permutation test, and the
      associated P-value and false discovery rate (FDR) are included in the output
      alongside the genes that are detected by user-defined criteria. A visualization
      plot is provided to view actual expression levels for each gene with estimated
      significance measurements. AVAILABILITY: RankProd is available at Bioconductor
      http://www.bioconductor.org. A web-based interface will soon be available at
      http://cactus.salk.edu/RankProd

PMID- 16982709
TI  - Concept inventing: continuing clarification.

PMID- 16982710
TI  - On joy-sorrow: a paradoxical pattern of human becoming.
AB  - The idea of paradox is central to Parse's human becoming theory. Joy-sorrow is an
      example of a paradoxical pattern of human becoming which was earlier investigated
      by Parse, using her research method. Here, the concept is revisited and further
      explored in light of selected literature, including a classic work on grief and
      other writings on aesthetic experience. Connections are also drawn between joy
      sorrow and the Japanese concept of wabi-sabi.

PMID- 16982711
TI  - Joy-sorrow revisited.

PMID- 16982713
TI  - Studying synchronicity related to dead loved ones AKA after-death communication:
      Martha, what do you think?

PMID- 16982712
TI  - Dying and grieving seen through a unitary lens.
AB  - In this column, Todaro-Franceschi presents a unitary view of energy, grounded
      within Rogers' (1992) science of unitary human beings, that supports a new view
      of dying and grieving, one based on the assumption that energy transforms, but is
      never lost. She briefly discusses her research on synchronicities related to dead
      loved ones as a basis for a new healing modality for the bereaved. Pilkington
      summarizes five studies on the lived experience of grieving within Parse's human
      becoming theory that were conducted either by her or William Cody. The unified
      description that emerged can assist nurses in being truly present with those who
      are grieving a loss.

PMID- 16982714
TI  - Developing nursing knowledge on grieving: a human becoming perspective.

PMID- 16982715
TI  - Living ethics: contributing to knowledge building through qualitative inquiry.
AB  - In this column, the authors discuss ethical and scientific standards in research
      and publication in light of their worldviews; human science; human becoming; and
      Parse's conceptual, ethical, methodological, and interpretive dimensions of the
      research process.

PMID- 16982716
TI  - Teaching the abyss: living the art-science of nursing.
AB  - This column addresses how nurse educators can provide the teaching-learning
      experiences for novice nurses to develop the leadership competence to effectively
      practice nursing in an extremely demanding healthcare environment. The authors
      delve into Mitchell and Bunkers' use of the metaphor of an abyss to explore the
      lived experience of risking being with others in extremely intense interpersonal
      situations. Using reflection, students' journal narratives affirm connections
      made among past experiences and the new knowledge gleaned from exploring and
      naming the phenomenon of the abyss. Several teaching-learning strategies are
      offered as ways for addressing the leadership issues related to dealing with
      intense relational experiences in nursing practice, including exploring nurse
      theorist Rosemarie Rizzo Parse's essentials of leadership.

PMID- 16982717
TI  - Jo Ann Ashley 30 years later: legacy for practice.
AB  - Jo Ann Ashley, nurse scholar, educator, and feminist activist died at age 41 in
      1980. Ashley illuminated the historical foundations of modern medicine, nursing,
      and hospital care in her pivotal book published in 1976, Hospitals, Paternalism,
      and the Role of the Nurse. Ashley's innovative research uncovered a web of
      pervasive gender and class bias in the delivery of healthcare in the United
      States. This column commemorates the 30-year anniversary of that publication with
      a remembrance of her life and ideas. It examines Ashley's relevance for nursing
      theory and current practice through an analysis of her many scholarly works and
      through interviews with those who knew her.

PMID- 16982718
TI  - Human becoming-guided practice.

PMID- 16982719
TI  - Newman's health as expanding consciousness.

PMID- 16982720
TI  - A perspective on Watson's theory of human caring.

PMID- 16982721
TI  - Humanistic nursing, interpersonal relations theory, and the empathy-altruism
      hypothesis.
AB  - The purpose of this paper is to illuminate the relevance and applicability of
      theory for nursing research and practice. Following a brief explanation of the
      four levels of theoretical abstraction recognized by nursing, Paterson and
      Zderad's humanistic nursing theory and Peplau's theory of interpersonal relations
      are described. In addition, one social psychology theory, the empathy-altruism
      hypothesis, is also explained. The value and implications of the three theories
      for nursing research and practice are discussed, and several research questions
      are proposed.

PMID- 16982722
TI  - A phenomenological study: the lived experience of persons having a different
      sense of hearing.
AB  - Living with a different sense of hearing, including loss of hearing, is a
      worldwide phenomenon, known to be a silencing condition that can change persons'
      patterns of relating and divest effective ways of giving and receiving messages
      of sound. This research describes the meaning of this experience for 7
      participants. The researcher followed Giorgi's descriptive phenomenological
      method for analysis-synthesis to arrive at a general structural description of
      the experience. Parse's theory of human becoming framed the researcher's
      theoretical perspective. Findings build on Parse's theory and may enhance nurses'
      understanding, in turn altering the way nurses approach persons having a
      different sense of hearing.

PMID- 16982723
TI  - A process model of healing and personal transformation in persons with chronic
      skin wounds.
AB  - Utilizing Newman's research as praxis process, this research examined the
      patterns of those living with chronic skin wounds. Ten men and 8 women, primarily
      of retirement age and living with chronic skin wounds for a year or more,
      reflected upon important relationships and life events during two in-depth
      interviews and a self-expressive drawing. Emerging from each participant's
      pattern was the link among human development, expanding consciousness, and
      processing a serious physical threat. Considering data across participants, five
      themes emerged from the data with evolution of a process model of wholistic
      healing that has implications for advanced nursing practice.

PMID- 16982724
TI  - Nursing in Turkey.
AB  - The current discussion on the nursing shortage needs to focus as much on nursing
      job satisfaction and retention as on nursing recruitment and education. Selected
      aspects of the motivational psychology of Abraham Maslow, Mihaly
      Csikszentmihalyi, and Frederick Hertzberg are here discussed in light of the
      challenges-opportunities of nursing in Turkey and elsewhere. Also discussed is an
      innovative program to support the application of nursing theory and professional
      development in Toronto, Canada.

PMID- 16982725
TI  - Nursing satisfaction and job enrichment in Turkey.
AB  - Survey research was conducted with the aim of better understanding nurses'
      perceptions of organizational factors which relate to their job satisfaction and
      motivation in Turkey. Nurses (N = 290) who were employed at a training and
      research hospital, part of the Turkish Republic Ministry of Health, were
      included. The questionnaire used was developed for this study based on Hackman
      and Oldman's job enrichment theory. The results showed that only one third of the
      nurse leaders and one in five of the staff nurses reported being satisfied with
      their job. The participants saw the five core job dimensions of Hackman and
      Oldman's work design model: skill variety, task identity, task significance,
      autonomy, and feedback as important for nurses. Nursing was described by the
      participants as hard and challenging, but they also found it meaningful and said
      that it gave them the opportunity to use their skills and abilities.

PMID- 16982726
TI  - Health promotion in adolescents: a review of Pender's health promotion model.
AB  - Adolescents have unique health considerations as they transition from parent
      managed healthcare to personal responsibility for health behavior. One question
      to consider is the goodness-of-fit of available theoretical models for explaining
      and predicting adolescent health-promoting behavior. This integrative review
      explored Pender's health promotion model in relation to adolescent health.
      Specifically, this review summarizes the components of Pender's model and the
      supporting theoretical underpinnings based in the social cognitive theory.
      Research literature related to the health promotion model and various aspects of
      teen health is explored. Recommendations for further research and theory
      development are discussed.

PMID- 16982728
TI  - Cancer's molecular sweet tooth and the Warburg effect.
AB  - More than 80 years ago, the renowned biochemist Otto Warburg described how cancer
      cells avidly consume glucose and produce lactic acid under aerobic conditions.
      Recent studies arguing that cancer cells benefit from this phenomenon, termed the
      Warburg effect, have renewed discussions about its exact role as cause,
      correlate, or facilitator of cancer. Molecular advances in this area may reveal
      tactics to exploit the cancer cell's "sweet tooth" for cancer therapy.

PMID- 16982729
TI  - Interplay between Notch signaling and epigenetic silencers in cancer.
AB  - Given its role in the development and self-renewal of many tissues, it is not
      surprising that a prominent role has recently been proposed for the Notch signal
      transduction pathway in tumor development. However, exactly how Notch
      hyperactivation promotes oncogenesis is poorly understood. Recent findings in
      Drosophila melanogaster have linked the Notch pathway to epigenetic silencing and
      the tumor suppressor gene Rb during tumorigenesis. Because aberrant epigenetic
      gene silencing contributes to the pathogenesis of most human cancers, these
      findings may provide a new focal point to understand how Notch is associated with
      cancers, and to help develop better selective cancer therapies.

PMID- 16982730
TI  - Small molecules, big players: the National Cancer Institute's Initiative for
      Chemical Genetics.
AB  - In 2002, the National Cancer Institute created the Initiative for Chemical
      Genetics (ICG), to enable public research using small molecules to accelerate the
      discovery of cancer-relevant small-molecule probes. The ICG is a public-access
      research facility consisting of a tightly integrated team of synthetic and
      analytical chemists, assay developers, high-throughput screening and automation
      engineers, computational scientists, and software developers. The ICG seeks to
      facilitate the cross-fertilization of synthetic chemistry and cancer biology by
      creating a research environment in which new scientific collaborations are
      possible. To date, the ICG has interacted with 76 biology laboratories from 39
      institutions and more than a dozen organic synthetic chemistry laboratories
      around the country and in Canada. All chemistry and screening data are deposited
      into the ChemBank web site (http://chembank.broad.harvard.edu/) and are available
      to the entire research community within a year of generation. ChemBank is both a
      data repository and a data analysis environment, facilitating the exploration of
      chemical and biological information across many different assays and small
      molecules. This report outlines how the ICG functions, how researchers can take
      advantage of its screening, chemistry and informatic capabilities, and provides a
      brief summary of some of the many important research findings.

PMID- 16982731
TI  - EPHB4 and survival of colorectal cancer patients.
AB  - The family of receptor tyrosine kinases EPH and their Ephrin ligands regulate
      cell proliferation, migration, and attachment. An important role in colorectal
      carcinogenesis is emerging for some of its members. In this study, we evaluate
      the role of EPHB4 in colorectal cancer and its value as a prognostic marker.
      EPHB4 levels were assessed by immunohistochemical staining of tissue microarrays
      of 137 colorectal tumors and aberrant hypermethylation of the EPHB4 promoter was
      investigated using methylation-specific PCR. We found that EPHB4 expression is
      frequently reduced or lost in colorectal tumors. Patients with low EPHB4 tumor
      levels had significantly shorter survival than patients in the high EPHB4 group
      (median survival, 1.8 and >9 years, respectively; P < 0.01, log-rank test), and
      this finding was validated using an independent set of 125 tumor samples. In
      addition, we show that EPHB4 promoter hypermethylation is a common mechanism of
      EPHB4 inactivation. Moreover, reintroduction of EPHB4 resulted in a significant
      reduction in the clonogenic potential of EPHB4-deficient cells, whereas
      abrogation of EPHB4 in cells with high levels of this receptor lead to a
      significant increase in clonogenicity. In summary, we identified EPHB4 as a
      useful prognostic marker for colorectal cancer. In addition, we provide
      mechanistic evidence showing that promoter methylation regulates EPHB4
      transcription and functional evidence that EPHB4 can regulate the long-term
      clonogenic potential of colorectal tumor cells, revealing EPHB4 as a potential
      new tumor suppressor gene in colorectal cancer.

PMID- 16982732
TI  - A mouse model for the molecular characterization of brca1-associated ovarian
      carcinoma.
AB  - Little is known about the mechanisms that underlie Brca1-associated ovarian
      tumorigenesis, mainly due to the lack of an appropriate experimental model. We
      developed genetically defined primary mouse ovarian surface epithelial (OSE) cell
      lines in which the loss of functional Brca1 and p53 recapitulates the events that
      are thought to occur in early ovarian cancer development in patients with Brca1
      mutations. This system allows for the introduction of additional oncogenes that
      are thought to cooperate with the loss of Brca1 and p53 to induce tumorigenesis.
      We showed that Myc is sufficient to induce transformation of ovarian cells that
      are deficient for both Brca1 and p53 but not sufficient for the transformation of
      cells that are deficient for either Brca1 or p53. The transformed Brca1-deficient
      OSE cells display an increased number of centrosomes, acquire complex chromosome
      aberrations, and lack Rad51 nuclear foci in the presence of DNA-damaging agents,
      such as mitomycin C and cisplatin. Immunocompetent mice injected with transformed
      OSE cells develop tumors that resemble human metastatic serous ovarian carcinoma,
      the most common type of ovarian cancer in women. Consistent with the reported
      platinum chemosensitivity in patients with Brca1-associated ovarian cancer, the
      Brca1-deficient OSE cells have increased sensitivity to the DNA-damaging agent
      cisplatin, whereas sensitivity to the microtubule poison paclitaxel is similar
      between Brca1 wild-type and Brca1-deficient cells. The Brca1 wild-type and Brca1
      deficient mouse ovarian tumors and cell lines provide a new experimental system
      for the evaluation of therapies that target the Brca1 pathway.

PMID- 16982733
TI  - Inhibition of mitogen-elicited signal transduction and growth in prostate cancer
      with a small peptide derived from the functional domain of DOC-2/DAB2 delivered
      by a unique vehicle.
AB  - Differentially expressed in ovarian cancer-2/disabled 2 (DOC-2/DAB2) protein,
      often lost in prostate cancer and other cancer types, is a part of homeostatic
      machinery in normal prostate epithelium. DOC-2/DAB2 modulates mitogen-elicited
      mitogen-activated protein kinase (MAPK) signal transduction by sequestering
      several adaptor or effector molecules, such as growth factor receptor bound
      protein 2 and c-Src. We have shown that the proline-rich sequence in DOC-2/DAB2
      is the key functional domain for this action. In this study, we further
      synthesized peptide based on the functional proline-rich domain and examined its
      biological function in prostate cancer using cell-permeable peptide (CPP) as a
      delivery system. From screening of several CPPs in prostate cancer cell lines, a
      polyarginine peptide (R11) seemed to be the best delivery vehicle because of its
      highly efficient uptake. In addition, we also observed a similar in vitro half
      life and cellular location of R11 in four different prostate cancer cell lines.
      By conjugating a proline-rich sequence (PPL) or control sequence (AAL) derived
      from DOC-2/DAB2 to the COOH terminus of R11, we showed that R11PPL but not R11 or
      R11AAL was able to suppress either serum- or androgen-induced cell proliferation
      in prostate cancer cells without endogenous DOC-2/DAB2 expression. Consistently,
      the activation status of MAPK elicited by these mitogens was significantly
      inhibited by R11PPL but not by R11AAL or R11. Taken together, we conclude that a
      functional peptide derived from proline-rich domain in DOC-2/DAB2 has growth
      inhibitory activity as its native protein, and CPP seems to be an efficient
      delivery system in prostate cancer cells.

PMID- 16982734
TI  - Asynchronous growth of prostate cancer is reflected by circulating tumor cells
      delivered from distinct, even small foci, harboring loss of heterozygosity of the
      PTEN gene.
AB  - The clinical value of prostate-specific antigen (PSA)-positive circulating tumor
      cells (CTCs) is still a matter of debate and it is also still unclear if these
      CTCs actually represent the primary tumor. Therefore, we isolated PSA-positive
      CTCs from the peripheral blood of patients suffering from multifocal cancers and
      did genetic profiling of each cancer focus by a multiplex PCR-based
      microsatellite analysis (D7S522, D8S522, NEFL, D10S541, D13S153, D16S400,
      D16S402, D16S422, and D17S855). In 17 of 20 prostate cancer cases, the loss of
      heterozygosity (LOH) pattern of the CTCs was identical with only one focus of the
      primary tumor. Moreover, in six cases, the LOH pattern suggested that smaller
      foci, down to 0.2 cm3, might deliver CTCs. Interestingly, the highest number of
      LOHs was observed at the marker D10S541 (85%), the PTEN gene, which was observed
      much less frequently in unifocal prostate cancer (48%). Furthermore, the
      infrequently occurring LOH in the BRCA1 gene (38%) was found in four of the five
      cases where a biochemical recurrence was seen within 3 years after prostatectomy.
      Therefore, the data might support the assumption that CTCs in prostate cancer are
      derived from distinct foci of a primary tumor. The size of the tumor focus is not
      related to the delivery of cells. Although the number of cases that were
      investigated in this study was small, it might be suggested that the LOH at
      distinct markers such as D10S541 and D17S855 represent the genes PTEN and BRCA1,
      which might be associated with the occurrence of CTCs in the peripheral blood of
      patients as well as an early biochemical recurrence.

PMID- 16982735
TI  - Rare germ line CHEK2 variants identified in breast cancer families encode
      proteins that show impaired activation.
AB  - Germ line mutations in CHEK2, the gene that encodes the Chk2 serine/threonine
      kinase activated in response to DNA damage, have been found to confer an
      increased risk of some cancers. We have previously reported the presence of the
      common deleterious 1100delC and four rare CHEK2 mutations in inherited breast
      cancer. Here, we report that predictions made by bioinformatic analysis on the
      rare mutations indicate that two of these, delE161 (483-485delAGA) and R117G, are
      likely to be deleterious. We show that the proteins encoded by 1100delC and
      delE161 are both unstable and inefficiently phosphorylated at Thr68 in response
      to DNA damage, a step necessary for the oligomerization of Chk2. Oligomerization
      is in turn necessary for additional phosphorylation and full activation of the
      protein. A second rare mutation, R117G, is phosphorylated at Thr68 but fails to
      show a mobility shift on DNA damage, suggesting that it fails to become further
      phosphorylated and hence fully activated. Our results indicate that delE161 and
      R117G encode nonfunctional proteins and are therefore likely to be pathogenic.
      The findings from the biochemical analysis correlate well with predictions made
      by bioinformatics analysis. In addition, the results imply that these mutations,
      as well as 1100delC, cannot act in a dominant-negative manner to cause cancer,
      and tumorigenesis in association with these mutations may be due to
      haploinsufficiency.

PMID- 16982736
TI  - Autoantibody cancer biomarker: extracellular protein kinase A.
AB  - In cancer cells, cyclic AMP-dependent protein kinase (PKA) is secreted into the
      conditioned medium. This PKA, designated as extracellular protein kinase A
      (ECPKA), is markedly up-regulated in the sera of patients with cancer. The
      currently available tumor markers are based on the antigen determination method
      and lack specificity and sensitivity. Here, we present an ECPKA autoantibody
      detection method for a universal biomarker that detects cancer of various cell
      types. We tested sera from 295 patients with cancers of various cell types, 155
      normal controls, and 55 patients without cancer. The specificity and sensitivity
      of this autoantibody enzyme immunoassay method were compared with the
      conventional antigen determination method by receiver-operating characteristic
      plots. In the sera, the presence of autoantibody directed against ECPKA was
      highly correlated with cancer. High anti-ECPKA autoantibody titers (frequency,
      90%; mean titer, 3.0) were found in the sera of patients with various cancers,
      whereas low or negative titers (frequency, 12%; mean titer, 1.0) were found in
      the control group. The receiver-operating characteristic plot showed that
      autoantibody enzyme immunoassay exhibited 90% sensitivity and 88% specificity,
      whereas the enzymatic assay exhibited 83% sensitivity and 80% specificity. These
      results show that the autoantibody method distinguished between patients with
      cancer and controls better than the antigen method could. Our results show that
      autoantibody ECPKA is a universal serum biomarker for cancers of various cell
      types.

PMID- 16982737
TI  - Role of apoptotic nuclease caspase-activated DNase in etoposide-induced treatment
      related acute myelogenous leukemia.
AB  - Etoposide-induced treatment-related acute myelogenous leukemia (t-AML) is
      characterized by rearrangements of the mixed lineage leukemia (MLL) gene with one
      of its >50 partner genes, most probably as a consequence of etoposide-induced DNA
      double-strand breaks (DSBs). Recent studies have shown that etoposide-induced
      DSBs occur predominantly within the breakpoint cluster region (bcr) of the MLL
      gene. However, bcr-specific DSBs induced by etoposide are not topoisomerase II
      linked but the result of apoptotic nuclease-mediated DNA cleavage. Here, we test
      the involvement of caspase-activated DNase (CAD) and other apoptotic components
      in etoposide-induced gene rearrangements using two methods. First, we measured
      the effect of etoposide on the integration frequency of a transfected plasmid.
      Etoposide strongly stimulated plasmid integration in CAD cDNA-complemented mouse
      embryonic fibroblasts (MEFs) but not in CAD knockout (KO) MEFs. Consistently,
      down-regulation of ICAD (inhibitor of CAD, also required for proper folding of
      CAD) in an HT29-derived cell line, which leads to decreased CAD activity,
      significantly reduced etoposide-induced plasmid integration. Second, we used long
      template inverse PCR to focus on gene rearrangements at the MLL locus. Etoposide
      stimulated MLL fusion product formation in CAD cDNA-complemented MEFs but not in
      CAD KO MEFs. Together, these results suggest that CAD and other apoptotic
      components may play an important role in etoposide-induced t-AML.

PMID- 16982738
TI  - Implications of gene-environment interaction in studies of gene variants in
      breast cancer: an example of dietary isoflavones and the D356N polymorphism in
      the sex hormone-binding globulin gene.
AB  - Studies to identify common genetic variants contributing to breast cancer risk
      often yield inconsistent results. Breast cancer is a complex disease involving
      both genetic and environmental determinants. Dietary isoflavones are thought to
      reduce breast cancer risk by stimulating circulating sex hormone-binding globulin
      (SHBG) levels. The SHBG gene contains a D356N polymorphism and the N variant is
      associated with reduced SHBG clearance compared with the D variant. In this
      study, we show a significant gene-environment interaction between SHBG D356N
      polymorphism and dietary isoflavone exposure on circulating SHBG levels in 1,988
      postmenopausal women. SHBG levels were positively associated with isoflavones in
      women carrying the N variant (etap2 = 1.9%; P = 0.006) but not in women carrying
      only the D variant (etap2 = 0.0%; P = 0.999; P(interaction) = 0.019). This
      finding shows that the subtle effects of some genetic variants may be magnified
      and only become detectable in the presence of certain exposures. This gene
      environment interaction might explain heterogeneity in studies associating SHBG
      gene variants and soy consumption with breast cancer risk in Far East population
      exposed to high isoflavone levels compared with populations with lower levels.

PMID- 16982739
TI  - Array comparative genomic hybridization reveals distinct DNA copy number
      differences between gastrointestinal stromal tumors and leiomyosarcomas.
AB  - Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation.
      Until recently, most gastrointestinal stromal tumors (GIST) were also classified
      as smooth muscle tumors, but now GISTs are recognized as a separate entity,
      defined as spindle cell and/or epithelioid tumors localized in the
      gastrointestinal tract. Using microarray-based comparative genomic hybridization
      (array CGH), we have created a detailed map of DNA copy number changes for 7
      GISTs and 12 leiomyosarcomas. Considerable gains and losses of chromosomal
      segments were observed in both tumor types. The most frequent aberration observed
      in GISTs was loss of chromosomes 14 and 22, with minimal recurrent regions in
      14q11.2-q32.33 (71% of the tumors) and 22q12.2-q13.31 (100%). In leiomyosarcomas,
      frequent loss of chromosome 10 and 13q was observed, with minimal recurrent
      regions in 10q21.3 (75%) and 13q14.2-q14.3 (75%). Recurrent high-level
      amplification of 17p13.1-p11.2 was detected in leiomyosarcomas. Expression
      profiling using cDNA microarrays revealed four candidate genes in this region
      with high expression (AURKB, SREBF1, MFAP4, and FLJ10847). Altered expression of
      AURKB and SREBF1 has been observed previously in other malignancies. Hierarchical
      clustering of all samples separated GISTs and leiomyosarcomas into two distinct
      clusters. Statistical analysis identified six chromosomal regions, 1p36.11-p13.1,
      9q21.11-9q34.3, 14q11.2-q23.2, 14q31.3-q32.33, 15q24.3-q26.3, and 22q11.21
      q13.31, which were significantly different in copy number between GISTs and
      leiomyosarcomas. Our results show the potential of using array comparative
      genomic hybridization to classify histologically similar tumors such as GISTs and
      leiomyosarcomas.

PMID- 16982740
TI  - MCT-1 protein interacts with the cap complex and modulates messenger RNA
      translational profiles.
AB  - MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and
      has been shown to induce cell proliferation as well as activate survival-related
      pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain
      that is found in several tRNA and rRNA modification enzymes. Here, we established
      that MCT-1 protein interacts with the cap complex through its PUA domain and
      recruits the density-regulated protein (DENR/DRP), containing the SUI1
      translation initiation domain. Through the use of microarray analysis on polysome
      associated mRNAs, we showed that up-regulation of MCT-1 was able to modulate the
      translation profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs, despite
      equivalent levels of mRNAs in the cytoplasm. Our data establish a role for MCT-1
      in translational regulation, and support a linkage between translational control
      and oncogenesis.

PMID- 16982741
TI  - The expression of CD30 in anaplastic large cell lymphoma is regulated by
      nucleophosmin-anaplastic lymphoma kinase-mediated JunB level in a cell type
      specific manner.
AB  - Chromosomal translocation t(2;5) and the resulting fusion protein nucleophosmin
      anaplastic lymphoma kinase (NPM-ALK) are detected in 50% to 70% of anaplastic
      large cell lymphoma (ALCL), which is a T/null cell non-Hodgkin's lymphoma showing
      anaplastic morphology with cell surface expression of CD30. Because aberrant CD30
      expression was also observed in the T-cell lymphoma derived from lineage-specific
      NPM-ALK transgenic mice, we tested the hypothesis that there might be a
      functional relationship between the two neoplastic-related proteins: NPM-ALK and
      CD30. In this study, we used the RNA interference method to modulate NPM-ALK
      protein expression in ALCL-derived, t(2;5)-positive Karpas 299 cells. We observed
      decreased CD30 expression when NPM-ALK was repressed. Further analysis suggested
      that JunB functioned as the mediator of NPM-ALK-derived CD30 transcriptional
      regulation. The NPM-ALK-repressed cells, which had low CD30 expression, were
      characterized with lower cell proliferation compared with cells in the control
      group, suggesting that altered CD30 expression may correlate to NPM-ALK-mediated
      tumor cell growth inhibition. Combination of NPM-ALK repression and CD30 ligand
      leads to significantly increased tumor cell growth inhibition compared with one
      method alone, suggesting its potential application for ALCL-specific cancer
      treatment.

PMID- 16982742
TI  - Hypoxic stress induces dimethylated histone H3 lysine 9 through histone
      methyltransferase G9a in mammalian cells.
AB  - Dimethylated histone H3 lysine 9 (H3K9me2) is a critical epigenetic mark for gene
      repression and silencing and plays an essential role in embryogenesis and
      carcinogenesis. Here, we investigated the effects of hypoxic stress on H3K9me2 at
      both global and gene-specific level. We found that hypoxia increased global
      H3K9me2 in several mammalian cell lines. This hypoxia-induced H3K9me2 was
      temporally correlated with an increase in histone methyltransferase G9a protein
      and enzyme activity. The increase in H3K9me2 was significantly mitigated in G9a-/
      mouse embryonic stem cells following hypoxia challenge, indicating that G9a was
      involved in the hypoxia-induced H3K9me2. In addition to the activation of G9a,
      our results also indicated that hypoxia increased H3K9me2 by inhibiting H3K9
      demethylation processes. Hypoxic mimetics, such as deferoxamine and
      dimethyloxalylglycine, were also found to increase H3K9me2 as well as G9a protein
      and activity. Finally, hypoxia increased H3K9me2 in the promoter regions of the
      Mlh1 and Dhfr genes, and these increases temporally correlated with the
      repression of these genes. Collectively, these results indicate that G9a plays an
      important role in the hypoxia-induced H3K9me2, which would inhibit the expression
      of several genes that would likely lead to solid tumor progression.

PMID- 16982743
TI  - Cytogenetic instability in ovarian epithelial cells from women at risk of ovarian
      cancer.
AB  - Fanconi anemia is an inherited cancer predisposition disease characterized by
      cytogenetic and cellular hypersensitivity to cross-linking agents. Seeking
      evidence of Fanconi anemia protein dysfunction in women at risk of ovarian
      cancer, we screened ovarian surface epithelial cells from 25 primary cultures
      established from 22 patients using cross-linker hypersensitivity assays. Samples
      were obtained from (a) women at high risk for ovarian cancer with histologically
      normal ovaries, (b) ovarian cancer patients, and (c) a control group with no
      family history of breast or ovarian cancer. In chromosomal breakage assays, all
      control cells were mitomycin C (MMC) resistant, but eight samples (five of the
      six high-risk and three of the eight ovarian cancer) were hypersensitive.
      Lymphocytes from all eight patients were MMC resistant. Only one of the eight
      patients had a BRCA1 germ-line mutation and none had BRCA2 mutations, but FANCD2
      was reduced in five of the eight. Ectopic expression of normal FANCD2 cDNA
      increased FANCD2 protein and induced MMC resistance in both hypersensitive lines
      tested. No FANCD2 coding region or promoter mutations were found, and there was
      no genomic loss or promoter methylation in any Fanconi anemia genes. Therefore,
      in high-risk women with no BRCA1 or BRCA2 mutations, tissue-restricted
      hypersensitivity to cross-linking agents is a frequent finding, and chromosomal
      breakage responses to MMC may be a sensitive screening strategy because
      cytogenetic instability identified in this way antedates the onset of carcinoma.
      Inherited mutations that result in tissue-specific FANCD2 gene suppression may
      represent a cause of familial ovarian cancer.

PMID- 16982744
TI  - Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear
      factor-kappaB.
AB  - Daxx is a nuclear protein that localizes to PML oncogenic domains, sensitizes
      cells to apoptosis, and functions as a transcriptional repressor. We found that
      Daxx represses the expression of several antiapoptotic genes regulated by nuclear
      factor-kappaB, including cIAP2, in human tumor cell lines. Daxx interacts with
      RelB and inhibits RelB-mediated transcriptional activation of the human cIAP2
      gene promoter. Daxx also forms complexes with RelB while bound to its target
      sites in the cIAP2 promoter, as shown by electrophoretic mobility shift assays
      and chromatin immunoprecipitation experiments. Using cells from daxx-/- mouse
      embryos, we observed that levels of the corresponding murine c-IAP mRNA and
      protein are increased in cells lacking Daxx. Conversely, c-IAP mRNA and protein
      levels were reduced in relB-/- cells. Taken together, these observations provide
      a mechanism that links two previously ascribed functions of Daxx: transcriptional
      repression and sensitization to apoptosis.

PMID- 16982745
TI  - A human cell-based assay to evaluate the effects of alterations in the MLH1
      mismatch repair gene.
AB  - We describe a new approach to investigate alterations in the human MLH1 mismatch
      repair (MMR) gene. This is based on complementation of the phenotype of a MLH1
      defective subclone of the ovarian carcinoma A2780 cells by transfection of
      vectors encoding altered MLH1 proteins. Measurements of resistance (tolerance) to
      methylating agents, mutation rate at HPRT, microsatellite instability (MSI), and
      steady-state levels of DNA 8-oxoguanine were used to define the MMR status of
      transfected clones. The approach was validated by transfecting cDNA of wild-type
      (WT) MLH1, cDNAs bearing two previously identified polymorphisms (I219V and
      I219L) and two with confirmed hereditary nonpolyposis colorectal cancer (HNPCC)
      syndrome mutations (G224D and G67R). A low-level expression of two MLH1
      polymorphisms partially reversed methylation tolerance and the mutator phenotype,
      including MSI. Higher levels of I219V resulted in full restoration of these
      properties to WT. Increased expression of I129L did not fully complement the MLH1
      defect, because there was a simultaneous escalation in the level of oxidative DNA
      damage. The findings confirmed the important relationship between deficient MMR
      and increased levels of oxidative DNA damage. Mutations from Italian HNPCC
      families (G224D, G67R, N635S, and K618A) were all ineffective at reversing the
      phenotype of the MLH1-defective A2780 cells. One (K618A) was identified as a low
      penetrance mutation based on clinical and genetic observations.

PMID- 16982746
TI  - Aberrant expression of a disintegrin and metalloproteinase 17/tumor necrosis
      factor-alpha converting enzyme increases the malignant potential in human
      pancreatic ductal adenocarcinoma.
AB  - A disintegrin and metalloproteinase (ADAM) molecules are known for their unique
      potential to combine adhesion, proteolysis, and signaling. To understand the role
      of ADAM17/tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in
      pancreatic ductal adenocarcinoma (PDAC), we investigated its expression,
      function, and in vitro regulation. ADAM17/TACE mRNA was expressed in 3 of 10
      normal pancreatic tissues, 6 of 8 samples from patients with chronic
      pancreatitis, 10 of 10 PDAC tissues, and 9 of 9 pancreatic cancer cell lines, but
      it was absent in primary duct epithelial cells. Immunohistochemical staining
      revealed positive cancer cells in 8 of 10 PDACs but no staining of ducts in
      normal pancreas. ADAM17/TACE was found in 0 of 16 pancreatic intraepithelial
      neoplasia (PanIN)-1A lesions, 1 of 30 PanIN-1B lesions, 2 of 13 PanIN-2 lesions
      but, in 13 of 15 PanIN-3 lesions, associated with PDAC. Western blot, flow
      cytometry, and confocal microscopy analyses showed the aberrant expression of
      ADAM17/TACE protein in pancreatic cancer cell lines. The proteolytic activity of
      ADAM17/TACE, assessed by the release of TNF-alpha, was inhibited by TNF-alpha
      protease inhibitor. ADAM17/TACE gene silencing using small interfering RNA
      technique in vitro reduced invasion behavior dramatically, whereas proliferation
      was unaffected. Furthermore, ADAM17/TACE mRNA expression was down-regulated in
      pancreatic cancer cells arrested in G2-M phase as well as in a time-dependent
      manner after TNF-alpha and interleukin-6 incubation. In conclusion, our findings
      provide evidence of aberrant expression of the proteolytically active ADAM17/TACE
      in advanced precursor lesions (PanIN-3) and PDAC while identifying its critical
      involvement in the invasion process.

PMID- 16982747
TI  - Tumor stromal-derived factor-1 recruits vascular progenitors to mitotic
      neovasculature, where microenvironment influences their differentiated
      phenotypes.
AB  - Mechanisms underlying tumor vasculogenesis, the homing and engraftment of bone
      marrow-derived vascular progenitors, remain undefined. We hypothesized that tumor
      cell-secreted factors regulate vasculogenesis. We studied vasculogenic and
      nonvasculogenic intracranial murine gliomas. A PCR screen identified stromal
      derived factor-1 (SDF-1/CXCL12) and vascular endothelial growth factor (VEGF)
      expression by vasculogenic glioma cells and spontaneously arising vasculogenic
      tumors in NF1+/-:Trp53+/- mice, but not by nonvasculogenic glioma cells. Enforced
      SDF-1, not VEGF, expression in nonvasculogenic cells caused vasculogenesis.
      Combined SDF-1 and VEGF expression augmented vasculogenesis over SDF-1 expression
      alone. Blocking SDF-1 receptor CXCR4 reduced short-term homing and long-term
      engraftment of vascular progenitors. Implanting tumor cells secreting SDF-1 was
      therefore necessary and sufficient to incorporate marrow-derived precursors into
      tumor endothelium. SDF-1 seemed to exert these effects by acting locally
      intratumorally and did not cause an efflux of marrow-derived progenitors into
      circulation. Tumor microenvironment determined additional fates of marrow-derived
      cells. Hypoxia, observed with ectopic s.c. murine tumors at levels approximating
      that of intracranial human glioblastoma, interacted with tumor-secreted SDF-1 to
      expand engrafted vascular progenitor differentiated phenotypes to include
      pericytes as well as endothelium. In contrast, less hypoxic orthotopic
      intracranial murine gliomas contained only marrow-derived endothelium without
      marrow-derived pericytes. Furthermore, we found that vasculogenesis is
      significant for tumors because it generates endothelium with a higher mitotic
      index than endothelium derived from local sources. Although CXCR4 blockade
      selectively targeted endothelium generated by vasculogenesis, completely
      inhibiting vessel formation may require combination therapy targeting locally
      derived and marrow-derived endothelium.

PMID- 16982748
TI  - Extracellular calcium as a candidate mediator of prostate cancer skeletal
      metastasis.
AB  - Prostate cancer almost exclusively metastasizes to skeletal sites, indicating
      that the bone provides a favorable microenvironment for its localization and
      progression. A natural yet understudied factor in bone that could facilitate
      tumor localization is elevated extracellular calcium ([Ca2+]o). The present study
      found that elevated [Ca2+]o (2.5 mmol/L) enhanced proliferation of skeletal
      metastatic prostate cell lines (PC-3 and C4-2B), but not the nonskeletal
      metastatic, epithelial-derived prostate cell line LNCaP. The proliferative effect
      of elevated [Ca2+]o was associated with higher expression of the calcium-sensing
      receptor (CaSR), a heterotrimeric G-protein-coupled receptor that is the
      predominant cell-surface sensor for [Ca2+]o. Knockdown of the CaSR via RNA
      interference reduced cell proliferation in vitro and metastatic progression in
      vivo. CaSR signaling in PC-3 cells was evaluated by measuring the elevated
      [Ca2+]o-dependent inhibition of cyclic AMP accumulation, induced by either
      prostaglandin E2 or forskolin. Elevated [Ca2+]o stabilized expression of cyclin
      D1, a protein required for cell cycle transition. Furthermore, elevated [Ca2+]o
      triggered activation of the Akt signaling pathway and enhanced PC-3 cell
      attachment. Both pertussis toxin (a G-protein inhibitor) and LY294002 (an
      inhibitor of Akt signaling) reduced cell attachment. These data suggest that
      elevated [Ca2+]o following increased bone remodeling could facilitate metastatic
      localization of prostate cancer via the CaSR and the Akt signaling pathway. Taken
      together, [Ca2+]o is a candidate mediator of prostate cancer bone metastasis.

PMID- 16982749
TI  - IQGAP1 protein specifies amplifying cancer cells in glioblastoma multiforme.
AB  - The accurate identification and thorough characterization of tumorigenic cells in
      glioblastomas are essential to enhance our understanding of their malignant
      behavior and for the design of strategies that target this important cell
      population. We report here that, in rat brain, the scaffolding protein IQGAP1 is
      a marker of brain nestin+ amplifying neural progenitor cells. In a rat model of
      glioma, IQGAP1 also characterizes a subpopulation of nestin+ amplifying tumor
      cells in glioblastoma-like tumors but not in tumors with oligodendroglioma
      features. We next confirmed that IQGAP1 represents a new marker that may help to
      discriminate human glioblastoma from oligodendrogliomas. In human glioblastoma
      exclusively, IQGAP1 specifies a subpopulation of amplifying nestin+ cancer cells.
      Neoplastic IQGAP1+ cells from glioblastoma can be expanded in culture and possess
      all the characteristics of cancer stem-like progenitors. The similarities between
      amplifying neural progenitors and glioblastoma amplifying cancer cells may have
      significant implications for understanding the biology of glioblastoma.

PMID- 16982750
TI  - Inhibition of the janus kinase family increases extracellular signal-regulated
      kinase 1/2 phosphorylation and causes endoreduplication.
AB  - The role of Janus-activated kinase (JAK) signaling in cell cycle transit and
      maintenance of genomic stability was determined in HL-60 myeloblastic leukemia
      cells. Inhibition of JAKs, all JAKs (JAK1, JAK2, JAK3, and tyrosine kinase 2),
      JAK2, or JAK3, caused a significant reduction in cell growth with a major G2-M
      arrest evident 24 hours after treatment. Targeting all JAKs also caused
      endoreduplication 48 and 72 hours after treatment. We discovered mitotic cells in
      both G2 (4N DNA) and G4 (8N DNA) subpopulations of cells treated with an
      inhibitor of all JAKs as detected by phosphorylated histone H3 expression.
      Treatment with inhibitors of just JAK2 or JAK3 drastically reduced such mitotic
      cells. We observed a complete blockage of IFN-gamma and interleukin-6-induced
      signal transducer and activator of transcription (STAT)-1 and STAT-3 response
      when all JAKs were inhibited. At the same time, we found baseline phosphorylated
      extracellular signal-regulated kinase (ERK) 1/2 to be elevated by JAK inhibition,
      particularly when all JAKs were inhibited. The G2-M arrest and endoreduplication
      induced by JAK inhibitors were reduced in cells pretreated with PD98059 to
      inhibit ERK. PD98059 also increased back the expression of the MAD2 cell cycle
      checkpoint protein that was down-regulated during "all JAKs inhibitor"-mediated
      endoreduplication. These data suggest that JAK signaling is needed for G2-M
      transit with inhibition of ERK.

PMID- 16982751
TI  - MicroRNA regulates the expression of human cytochrome P450 1B1.
AB  - MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression through
      translational repression or mRNA cleavage. Here, we found that cytochrome P450
      (CYP), a superfamily of drug-metabolizing enzymes, is a target of miRNA. Human
      CYP1B1, which is highly expressed in estrogen target tissues, catalyzes the
      metabolic activation of various procarcinogens and the 4-hydroxylation of 17beta
      estradiol. CYP1B1 protein is abundant in cancerous tissues. We identified a near
      perfect matching sequence with miR-27b in the 3'-untranslated region of human
      CYP1B1. Luciferase assays revealed that the reporter activity of the plasmid
      containing the miR-27b recognition element was decreased in MCF-7 cells (miR-27
      positive) but not in Jurkat cells (miR-27b negative). Exogenously expressed miR
      27b could decrease the luciferase activity in Jurkat cells. In MCF-7 cells, the
      antisense oligoribonucleotide for miR-27b restored the luciferase activity and
      increased the protein level and enzymatic activity of endogenous CYP1B1. These
      results suggested that human CYP1B1 is post-transcriptionally regulated by miR
      27b. The expression levels of miR-27b and CYP1B1 protein in breast cancerous and
      adjacent noncancerous tissues from 24 patients were evaluated. In most patients,
      the expression level of miR-27b was decreased in cancerous tissues, accompanied
      by a high level of CYP1B1 protein. A significant inverse association was observed
      between the expression levels of miR-27b and CYP1B1 protein. Thus, the decreased
      expression of miR-27b would be one of causes of the high expression of CYP1B1
      protein in cancerous tissues. This is the first study to show that miRNAs
      regulate not only essential genes for physiologic events but also drug
      metabolizing enzymes.

PMID- 16982752
TI  - HBXIP, cellular target of hepatitis B virus oncoprotein, is a regulator of
      centrosome dynamics and cytokinesis.
AB  - Hepatitis B virus accounts for more than 1 million cancer deaths annually, but
      the mechanism by which this virus promotes hepatocellular carcinoma remains
      unclear. The hepatitis B virus genome encodes an oncoprotein, HBx, which binds
      various cellular proteins including HBXIP. We show here that HBXIP is a regulator
      of centrosome duplication, required for bipolar spindle formation in HeLa human
      carcinoma cells and primary mouse embryonic fibroblast cells. We found that most
      cells deficient in HBXIP arrest in prometaphase with monopolar spindles whereas
      HBXIP overexpression causes tripolar or multipolar spindles due to excessive
      centrosome replication. Additionally, a defect in cytokinesis was seen in HBXIP
      deficient HeLa cells, with most cells failing to complete division and succumbing
      eventually to apoptosis. Expression of viral HBx in HeLa cells mimicked the
      effects of HBXIP overexpression, causing excessive centrosome replication,
      resulting in tripolar and multipolar spindles and defective cytokinesis.
      Immunolocalization and fluorescent protein tagging experiments showed that HBXIP
      associates with microtubules of dividing cells and colocalizes with HBx on
      centrosomes. Thus, viral HBx and its cellular target HBXIP regulate centrosome
      dynamics and cytokinesis affecting genetic stability. In vivo experiments using
      antisense oligonucleotides targeting HBXIP in a mouse model of liver regeneration
      showed a requirement for HBXIP for growth and survival of replicating
      hepatocytes. Thus, HBXIP is a critical regulator of hepatocyte cell growth in
      vivo, making it a strong candidate for explaining the tumorigenic actions of
      viral HBx.

PMID- 16982754
TI  - Death receptor-3, a new E-Selectin counter-receptor that confers migration and
      survival advantages to colon carcinoma cells by triggering p38 and ERK MAPK
      activation.
AB  - E-selectin-mediated adhesion of colon cancer cells to endothelial cells is a key
      event in metastasis. However, the signaling mechanisms that confer metastatic
      advantages to cancer cells adhering to E-selectin are ill defined. By using
      affinity column chromatography and pull-down assays on purified membrane extracts
      of HT29 and LoVo cells coupled to mass spectrometry analysis, we obtained the
      first evidence indicating that E-selectin binds to death receptor-3 (DR3)
      expressed by the cancer cells. Thereafter, we accumulated several results,
      suggesting that DR3 is an E-selectin receptor on colon cancer cells and that its
      activation by E-selectin triggers the activation of p38 and extracellular signal
      regulated kinase (ERK) mitogen-activated protein kinase (MAPK) and confers
      migration and survival advantages. First, by Western blotting, we found that the
      E-selectin-binding protein, identified as DR3, is recognized by two anti-DR3
      antibodies. Second, the neutralization of DR3 with an antibody and its knockdown
      by small interfering RNA decrease the adhesion of colon cancer cells to E
      selectin and E-selectin-expressing human umbilical vein endothelial cells. Third,
      inhibiting DR3 and knocking down its expression impair transendothelial migration
      of HT29 cells and block the activation of p38 and ERK by E-selectin. Fourth, high
      molecular weight isoforms of DR3 are expressed in samples of primary human colon
      carcinoma but not in samples from normal colon tissue. Intriguingly, DR3 is a
      death receptor but its activation by E-selectin does not induce apoptosis in
      colon cancer cells, except when ERK is inhibited. Our findings identify novel
      signaling and functional roles of DR3 activated in response to E-selectin and
      highlight the potential link between DR3 and metastasis.

PMID- 16982753
TI  - beta2-microglobulin is a signaling and growth-promoting factor for human prostate
      cancer bone metastasis.
AB  - The protein factor beta2-microglobulin (beta2M), purified from the conditioned
      medium of human prostate cancer cell lines, stimulated growth and enhanced
      osteocalcin (OC) and bone sialoprotein (BSP) gene expression in human prostate
      cancer cells by activating a cyclic AMP (cAMP)-dependent protein kinase A
      signaling pathway. When beta2M was overexpressed in prostate cancer cells, it
      induced explosive tumor growth in mouse bone through increased phosphorylated
      cAMP-responsive element binding protein (CREB) and activated CREB target gene
      expression, including OC, BSP, cyclin A, cyclin D1, and vascular endothelial
      growth factor. Interrupting the beta2M downstream signaling pathway by injection
      of the beta2M small interfering RNA liposome complex produced an effective
      regression of previously established prostate tumors in mouse bone through
      increased apoptosis as shown by immunohistochemistry and activation of caspase-9,
      caspase-3, and cleavage of poly(ADP-ribose) polymerase. These results suggest
      that beta2M signaling is an attractive new therapeutic target for the treatment
      of lethal prostate cancer bone metastasis.

PMID- 16982755
TI  - Epigenetic silencing of occludin promotes tumorigenic and metastatic properties
      of cancer cells via modulations of unique sets of apoptosis-associated genes.
AB  - Occludin is the first identified integral protein for the tight junction (TJ),
      and its long COOH-terminal domain is considered to have functions in receiving
      and transmitting cell survival signals. Loss of TJ-associated molecules, such as
      occludin, has been correlated with tumor progression in carcinogenesis; however,
      the precise molecular mechanisms explaining its loss of expression and whether
      occludin expression has any effects on cancer phenotypes remain to be clarified.
      Here, we show that forced expression of occludin in cancer cells exhibits
      enhanced sensitivity to differently acting apoptogenic factors, and thus inhibits
      the tumorigenicity of transformed cells, via modulation of unique sets of
      apoptosis-associated genes. In addition, studies using deletion mutants of
      occludin constructs show that 44 amino acids at the COOH-terminal end play a
      critical role in modifying the cellular phenotypes. Interestingly, occludin
      decreases cellular invasiveness and motility, thereby abrogating metastatic
      potencies of cancer cells. We also found that occludin expression is silenced by
      CpG island hypermethylation on its promoter region. Synergy with a demethylator
      and histone deacetylase inhibitor or retinoids that stimulate retinoic acid
      receptor alpha induces endogenous occludin, which is sufficient for apoptotic
      sensitization. Our results show the functional diversity of occludin and suggest
      that methylator phenotype of occludin provides enhanced tumorigenic, invasive,
      and metastatic properties of cancer cells, identifying occludin as a likely
      candidate for a tumor-suppressor gene in certain types of cancer.

PMID- 16982756
TI  - KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor
      tyrosine kinases, has antitumor activities and affects functional vascular
      properties.
AB  - Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis
      by stimulating the proangiogenic signaling of endothelial cells via activation of
      VEGF receptor (VEGFR) tyrosine kinases. Therefore, VEGFRs are an attractive
      therapeutic target for cancer treatment. In the present study, we show that a
      quinoline-urea derivative, KRN951, is a novel tyrosine kinase inhibitor for
      VEGFRs with antitumor angiogenesis and antigrowth activities. KRN951 potently
      inhibited VEGF-induced VEGFR-2 phosphorylation in endothelial cells at in vitro
      subnanomolar IC50 values (IC50 = 0.16 nmol/L). It also inhibited ligand-induced
      phosphorylation of platelet-derived growth factor receptor-beta (PDGFR-beta) and
      c-Kit (IC50 = 1.72 and 1.63 nmol/L, respectively). KRN951 blocked VEGF-dependent,
      but not VEGF-independent, activation of mitogen-activated protein kinases and
      proliferation of endothelial cells. In addition, it inhibited VEGF-mediated
      migration of human umbilical vein endothelial cells. Following p.o.
      administration to athymic rats, KRN951 decreased the microvessel density within
      tumor xenografts and attenuated VEGFR-2 phosphorylation levels in tumor
      endothelium. It also displayed antitumor activity against a wide variety of human
      tumor xenografts, including lung, breast, colon, ovarian, pancreas, and prostate
      cancer. Furthermore, dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) analysis revealed that a significant reduction in tumor vascular
      hyperpermeability was closely associated with the antitumor activity of KRN951.
      These findings suggest that KRN951 is a highly potent, p.o. active
      antiangiogenesis and antitumor agent and that DCE-MRI would be useful in
      detecting early responses to KRN951 in a clinical setting. KRN951 is currently in
      phase I clinical development for the treatment of patients with advanced cancer.

PMID- 16982757
TI  - Chemosensitization by knockdown of adenine nucleotide translocase-2.
AB  - Mitochondrial membrane permeabilization (MMP) is a rate-limiting step of
      apoptosis, including in anticancer chemotherapy. Adenine nucleotide translocase
      (ANT) mediates the exchange of ADP and ATP on the inner mitochondrial membrane in
      healthy cells. In addition, ANT can cooperate with Bax to form a lethal pore
      during apoptosis. Humans possess four distinct ANT isoforms, encoded by four
      genes, whose transcription depends on the cell type, developmental stage, cell
      proliferation, and hormone status. Here, we show that the ANT2 gene is up
      regulated in several hormone-dependent cancers. Knockdown of ANT2 by RNA
      interference induced no major changes in the aspect of the mitochondrial network
      or cell cycle but provoked minor increase in mitochondrial transmembrane
      potential and reactive oxygen species level and reduced intracellular ATP
      concentration without affecting glycolysis. At expression and functional levels,
      ANT2 depletion was not compensated by other ANT isoforms. Most importantly, ANT2,
      but not ANT1, silencing facilitated MMP induction by lonidamine, a mitochondrion
      targeted antitumor compound already used in clinical studies for breast, ovarian,
      glioma, and lung cancer as well as prostate adenoma. The combination of ANT2
      knockdown with lonidamine induced apoptosis irrespective of the Bcl-2 status.
      These data identify ANT2 as an endogenous inhibitor of MMP and suggest that its
      selective inhibition could constitute a promising strategy of chemosensitization.

PMID- 16982758
TI  - Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal
      tumor.
AB  - Inhibition of KIT oncoproteins by imatinib induces clinical responses in most
      gastrointestinal stromal tumor (GIST) patients. However, many patients develop
      imatinib resistance due to secondary KIT mutations. Heat shock protein 90 (HSP90)
      protects KIT oncoproteins from proteasome-mediated degradation, and we therefore
      did preclinical validations of the HSP90 inhibitor, 17-allylamino-18-demethoxy
      geldanamycin (17-AAG), in an imatinib-sensitive GIST cell line (GIST882) and in
      novel imatinib-resistant GIST lines that are either dependent on (GIST430 and
      GIST48) or independent of (GIST62) KIT oncoproteins. 17AAG (>100 nmol/L)
      inhibited imatinib-sensitive and imatinib-resistant KIT oncoproteins, with
      substantially reduced phospho-KIT and total KIT expression after 30 minutes and 6
      hours, respectively. KIT signaling intermediates, including AKT and mitogen
      activated protein kinase, were inactivated by 17-AAG in the KIT-positive GIST
      lines, but not in the KIT-negative GIST62. Likewise, cell proliferation and
      survival were inhibited in the KIT-positive GISTs but not in GIST62. These
      findings suggest that 17-AAG biological effects in KIT-positive GISTs result
      mainly from KIT oncoprotein inhibition. The dramatic inactivation of imatinib
      resistant KIT oncoproteins suggests that HSP90 inhibition provides a therapeutic
      solution to the challenge of heterogeneous imatinib resistance mutations in GIST
      patients.

PMID- 16982759
TI  - Therapeutic implications of a human neutralizing antibody to the macrophage
      stimulating protein receptor tyrosine kinase (RON), a c-MET family member.
AB  - RON is a member of the c-MET receptor tyrosine kinase family. Like c-MET, RON is
      expressed by a variety of epithelial-derived tumors and cancer cell lines and it
      is thought to play a functional role in tumorigenesis. To date, antagonists of
      RON activity have not been tested in vivo to validate RON as a potential cancer
      target. In this report, we used an antibody phage display library to generate IMC
      41A10, a human immunoglobulin G1 (IgG1) antibody that binds with high affinity
      (ED50 = 0.15 nmol/L) to RON and effectively blocks interaction with its ligand,
      macrophage-stimulating protein (MSP; IC50 = 2 nmol/L). We found IMC-41A10 to be a
      potent inhibitor of receptor and downstream signaling, cell migration, and
      tumorigenesis. It antagonized MSP-induced phosphorylation of RON, mitogen
      activated protein kinase (MAPK), and AKT in several cancer cell lines. In HT-29
      colon, NCI-H292 lung, and BXPC-3 pancreatic cancer xenograft tumor models, IMC
      41A10 inhibited tumor growth by 50% to 60% as a single agent, and in BXPC-3
      xenografts, it led to tumor regressions when combined with Erbitux. Western blot
      analyses of HT-29 and NCI-H292 xenograft tumors treated with IMC-41A10 revealed a
      decrease in MAPK phosphorylation compared with control IgG-treated tumors,
      suggesting that inhibition of MAPK activity may be required for the antitumor
      activity of IMC-41A10. To our knowledge, this is the first demonstration that a
      RON antagonist and specifically an inhibitory antibody of RON negatively affects
      tumorigenesis. Another major contribution of this report is an extensive analysis
      of RON expression in approximately 100 cancer cell lines and approximately 300
      patient tumor samples representing 10 major cancer types. Taken together, our
      results highlight the potential therapeutic usefulness of RON activity inhibition
      in human cancers.

PMID- 16982760
TI  - A dimeric peptide that binds selectively to prostate-specific membrane antigen
      and inhibits its enzymatic activity.
AB  - Prostate-specific membrane antigen (PSMA) is highly expressed by both normal and
      malignant prostate epithelial cells and by the neovasculature of many tumor
      types; however, it is not expressed by normal endothelial cells or other normal
      tissues. PSMA, therefore, represents an attractive candidate for selectively
      targeted therapies for prostate and/or other solid tumors. As an alternative
      approach to antibody-based anti-PSMA therapies, small peptides that bind
      selectively to PSMA-producing cells can be used to deliver cytotoxic drugs,
      protein toxins, and viruses selectively to malignant sites while minimizing
      systemic toxicity to normal tissues. Small peptides are relatively inexpensive to
      produce, not immunogenic, and easily coupled to cytotoxic agents. In the present
      study, a random phage library consisting of linear 12 amino acid peptides was
      used to identify peptides that bound selectively to PSMA. From a series of
      monomeric peptides, one with the sequence WQPDTAHHWATL was used to show binding
      of soluble peptide to PSMA. A dimeric version of this peptide showed markedly
      enhanced binding to soluble PSMA and an IC50 of 2.2 micromol/L for inhibition of
      PSMA enzymatic activity. Fluorescently labeled dimeric peptide bound selectively
      to PSMA-producing prostate cancer cells in vitro with no significant binding to
      non-PSMA-producing cells. Molecular modeling of the dimeric peptide revealed that
      histidine residues in close vicinity can efficiently coordinate a divalent ion
      and hold the peptide in a favorable configuration for binding and subsequent
      inhibition. These dimeric peptides, therefore, represent putative PSMA-selective
      targeting agents that are currently being evaluated for selective binding in
      vivo.

PMID- 16982761
TI  - Quantifying the activity of adenoviral E1A CR2 deletion mutants using renilla
      luciferase bioluminescence and 3'-deoxy-3'-[18F]fluorothymidine positron emission
      tomography imaging.
AB  - The adenoviral E1A CR2 mutant dl922-947 has potent activity in ovarian cancer. We
      have used Renilla luciferase bioluminescence imaging to monitor viral E1A
      expression and replication and [18F]fluorothymidine positron emission tomography
      ([18F]FLT-PET) to quantify the activity of dl922-947 in vivo. We created dlCR2
      Ren, with the same E1A CR2 deletion as dl922-947 and the luciferase gene from
      Renilla reniformis downstream of E1. Light emitted from s.c. and i.p. IGROV1
      ovarian carcinoma xenografts was measured following treatment with dlCR2 Ren.
      Mice bearing s.c. IGROV1 xenografts were injected with 2.96 to 3.7 MBq of
      [18F]FLT 48 and 168 hours following i.t. injection of dl922-947 or control virus
      Ad LM-X. The presence of Renilla luciferase in dlCR2 Ren did not reduce in vitro
      nor in vivo potency compared with dl922-947. Light emission correlated closely
      with E1A expression in vitro and peaked 48 hours after dlCR2 Ren injection in
      both s.c. and i.p. IGROV1 xenografts. It diminished by 168 hours in s.c. tumors
      but persisted for at least 2 weeks in i.p. models. Normalized tumor [18F]FLT
      uptake at 60 minutes (NUV60), fractional retention, and area under radioactivity
      curve all decreased marginally 48 hours after dl922-947 treatment and
      significantly at 168 hours compared with controls. There was a close linear
      correlation between NUV60 and both tumor proliferation (Ki67 labeling index) and
      thymidine kinase 1 expression. Renilla luciferase bioluminescence and [18F]FLT
      PET imaging are capable of quantifying the activity and effectiveness of E1A CR2
      deleted adenoviral mutants in ovarian cancer.

PMID- 16982762
TI  - PDZ-binding kinase/T-LAK cell-originated protein kinase, a putative cancer/testis
      antigen with an oncogenic activity in breast cancer.
AB  - Breast cancer is one of the most common cancers among women. To discover
      molecular targets that are applicable for development of novel breast cancer
      therapy, we previously did genome-wide expression profile analysis of 81 breast
      cancers and found dozens of genes that were highly and commonly up-regulated in
      breast cancer cells. Among them, we here focused on one gene that encodes PDZ
      binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), including a
      kinase domain. Northern blot analyses using mRNAs of normal human organs, breast
      cancer tissues, and cancer cell lines indicated this molecule to be a novel
      cancer/testis antigen. Reduction of PBK/TOPK expression by small interfering RNA
      resulted in significant suppression of cell growth probably due to dysfunction in
      the cytokinetic process. Immunocytochemical analysis with anti-PBK/TOPK antibody
      implicated a critical role of PBK/TOPK in an early step of mitosis. PBK/TOPK
      could phosphorylate histone H3 at Ser10 in vitro and in vivo, and mediated its
      growth-promoting effect through histone H3 modification. Because PBK/TOPK is the
      cancer/testis antigen and its kinase function is likely to be related to its
      oncogenic activity, we suggest PBK/TOPK to be a promising molecular target for
      breast cancer therapy.

PMID- 16982763
TI  - Magnetic resonance visualization of tumor angiogenesis by targeting neural cell
      adhesion molecules with the highly sensitive gadolinium-loaded apoferritin probe.
AB  - Tumor vessel imaging could be useful in identifying angiogenic blood vessels as
      well as being a potential predictive marker of antiangiogenic treatment response.
      We recently reported the expression of the neural cell adhesion molecule (NCAM)
      in the immature and tumor endothelial cell (TEC) lining vessels of human
      carcinomas. Exploiting an in vivo model of human tumor angiogenesis obtained by
      implantation of TEC in Matrigel in severe combined immunodeficiency mice, we
      aimed to image angiogenesis by detecting the expression of NCAM with magnetic
      resonance imaging. The imaging procedure consisted of (a) targeting NCAMs with a
      biotinylated derivative of C3d peptide that is known to have high affinity for
      these epitopes and (b) delivery of a streptavidin/gadolinium (Gd)-loaded
      apoferritin 1:1 adduct at the biotinylated target sites. The remarkable
      relaxation enhancement ability of the Gd-loaded apoferritin system allowed the
      visualization of TEC both in vitro and in vivo when organized in microvessels
      connected to the mouse vasculature. Gd-loaded apoferritin displayed good in vivo
      stability and tolerability. The procedure reported herein may be easily extended
      to the magnetic resonance visualization of other epitopes suitably targeted by
      proper biotinylated vectors.

PMID- 16982764
TI  - Alteration of the methylation status of tumor-promoting genes decreases prostate
      cancer cell invasiveness and tumorigenesis in vitro and in vivo.
AB  - We tested the hypothesis that cell invasiveness and tumorigenesis are driven by
      hypomethylation of genes involved in tumor progression. Highly invasive human
      prostate cancer cells PC-3 were treated with either the methyl donor S
      adenosylmethionine (SAM) or methyl DNA-binding domain protein 2 antisense
      oligonucleotide (MBD2-AS). Both treatments resulted in a dose- and time-dependent
      inhibition of key genes, such as urokinase-type plasminogen activator (uPA),
      matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor
      expression to decrease tumor cell invasion in vitro. No change in the levels of
      expression of genes already known to be methylated in late-stage prostate cancer
      cells, such as glutathione S-transferase P1 and androgen receptor, was seen.
      Inoculation of PC-3 cells pretreated with SAM and MBD2-AS into the flank of male
      BALB/c nu/nu mice resulted in the development of tumors of significantly smaller
      volume compared with animals inoculated with PC-3 cells treated with vehicle
      alone or MBD2 scrambled oligonucleotide. Immunohistochemical analysis of tumors
      showed the ability of SAM and MBD2-AS to significantly decrease tumoral uPA and
      MMP-2 expression along with levels of angiogenesis and survival pathway signaling
      molecules. Bisulfite sequencing analysis of tumoral genomic DNA showed that
      inhibition of both uPA and MMP-2 expression was due to methylation of their 5'
      regulatory region. These studies support the hypothesis that DNA hypomethylation
      controls the activation of multiple tumor-promoting genes and provide valuable
      insight into developing novel therapeutic strategies against this common disease,
      which target the demethylation machinery.

PMID- 16982765
TI  - Inhibition of hsp90 compromises the DNA damage response to radiation.
AB  - Inhibitors of the molecular chaperone Hsp90 have been shown to enhance tumor cell
      radiosensitivity. To begin to address the mechanism responsible, we have
      determined the effect of the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17
      demethoxygeldanamycin (17DMAG) on the DNA damage response to radiation. Exposure
      of MiaPaCa tumor cells to 17DMAG, which results in radiosensitization, inhibited
      the repair of DNA double-strand breaks according to gammaH2AX foci dispersal and
      the neutral comet assay. This repair inhibition was associated with reduced DNA
      PK catalytic subunit (DNA-PKcs) phosphorylation after irradiation and a
      disruption of DNA-PKcs/ErbB1 interaction. These data suggest that the previously
      established 17DMAG-mediated reduction in ErbB1 activity reduces its interaction
      with DNA-PKcs and thus accounts for the attenuation of radiation-induced DNA-PK
      activation. 17DMAG was also found to abrogate the activation of the G(2)- and S
      phase cell cycle checkpoints. Associated with these events was a reduction in
      radiation-induced ataxia-telangiectasia mutated (ATM) activation and foci
      formation in 17DMAG-treated cells. Although no interaction between ATM and Hsp90
      was detected, Hsp90 was found to interact with the MRE11/Rad50/NBS1 (MRN)
      complex. 17DMAG exposure reduced the ability of the MRN components to form
      nuclear foci after irradiation. Moreover, 17DMAG exposure reduced the interaction
      between NBS1 and ATM, although no degradation of the MRN complex was detected.
      These results suggest that the diminished radiation-induced activation of ATM in
      17DMAG-treated cells was the result of a compromise in the function of the MRN
      complex. These data indicate that Hsp90 can contribute to the DNA damage response
      to radiation affecting both DNA repair and cell cycle checkpoint activation.

PMID- 16982766
TI  - Role of p53 up-regulated modulator of apoptosis and phosphorylated Akt in
      melanoma cell growth, apoptosis, and patient survival.
AB  - Malignant melanoma is an aggressive and chemoresistant form of skin cancer
      characterized by rapid metastasis and poor patient prognosis. The development of
      innovative therapies with improved efficacy is critical to treatment of this
      disease. Here, we show that aberrant expression of two proteins, p53 up-regulated
      modulator of apoptosis (PUMA) and phosphorylated Akt (p-Akt), is associated with
      poor patient survival. Using tissue microarray analysis, we found that patients
      exhibiting both weak PUMA expression and strong p-Akt expression in their
      melanoma tumor tissue had significantly worse 5-year survival than patients with
      either weak PUMA or strong p-Akt expression alone (P < 0.001). Strikingly, no
      patients exhibiting strong PUMA expression and weak p-Akt expression in primary
      tumor tissue died within 5 years of diagnosis. We propose a two-pronged
      therapeutic strategy of (a) boosting PUMA expression and (b) inhibiting Akt
      phosphorylation in melanoma tumor tissue. Here, we report that a recombinant
      adenovirus containing human PUMA cDNA (ad-PUMA) efficiently inhibits human
      melanoma cell survival in vitro, rapidly induces apoptosis, and dramatically
      suppresses human melanoma tumor growth in a severe combined immunodeficient mouse
      xenograft model. In melanoma cells strongly expressing p-Akt, we show that
      Akt/protein kinase B signaling inhibitor-2 (API-2; a small-molecule Akt
      inhibitor) reduces cell survival in a dose- and time-dependent manner and
      enhances ad-PUMA-mediated growth inhibition of melanoma cells. Finally, we show
      that, by combining ad-PUMA and API-2 treatments, human melanoma tumor growth can
      be inhibited by >80% in vivo compared with controls. Our results suggest that a
      strategy to correct dysregulated PUMA and p-Akt expression in malignant melanoma
      may be an effective therapeutic option.

PMID- 16982767
TI  - Anticancer activity of BIM-46174, a new inhibitor of the heterotrimeric
      Galpha/Gbetagamma protein complex.
AB  - A large number of hormones and local agonists activating guanine-binding protein
      coupled receptors (GPCR) play a major role in cancer progression. Here, we
      characterize the new imidazo-pyrazine derivative BIM-46174, which acts as a
      selective inhibitor of heterotrimeric G-protein complex. BIM-46174 prevents the
      heterotrimeric G-protein signaling linked to several GPCRs mediating (a) cyclic
      AMP generation (Galphas), (b) calcium release (Galphaq), and (c) cancer cell
      invasion by Wnt-2 frizzled receptors and high-affinity neurotensin receptors
      (Galphao/i and Galphaq). BIM-46174 inhibits the growth of a large panel of human
      cancer cell lines, including anticancer drug-resistant cells. Exposure of cancer
      cells to BIM-46174 leads to caspase-3-dependent apoptosis and poly(ADP-ribose)
      polymerase cleavage. National Cancer Institute COMPARE analysis for BIM-46174
      supports its novel pharmacologic profile compared with 12,000 anticancer agents.
      The growth rate of human tumor xenografts in athymic mice is significantly
      reduced after administration of BIM-46174 combined with either cisplatin,
      farnesyltransferase inhibitor, or topoisomerase inhibitors. Our data validate the
      feasibility of targeting heterotrimeric G-protein functions downstream the GPCRs
      to improve anticancer chemotherapy.

PMID- 16982768
TI  - Identification of new compounds that trigger apoptosome-independent caspase
      activation and apoptosis.
AB  - Identification of alternative pathways of caspase activation is an important step
      to develop new antitumor treatments. We report here the result of a screening
      with a small chemical library, the Developmental Therapeutics Program-National
      Cancer Institute "challenge set," on cells expressing mutated caspase-9. We have
      identified two molecules capable of activating an apoptosome-independent
      apoptotic pathway. These compounds, named F6 and G5, target the ubiquitin
      proteasome system by inhibiting the ubiquitin isopeptidases. We have shown that
      F6 and G5 induce a rather unique apoptotic pathway, which includes a Bcl-2
      dependent but apoptosome-independent mitochondrial pathway with up-regulation of
      the BH3-only protein Noxa, stabilization of the inhibitor of apoptosis antagonist
      Smac, but also the involvement of the death receptor pathway. Noxa plays an
      important role in the induction of mitochondrial fragmentation and caspase
      activation, whereas the death receptor pathway becomes critical in the absence of
      a functional apoptosome. This study suggests that screening of chemical libraries
      on cancer cells with defined mutations in apoptotic key elements can lead to the
      identification of compounds that are useful to characterize alternative pathways
      of caspase activation.

PMID- 16982769
TI  - Adenomatous polyposis coli determines sensitivity to histone deacetylase
      inhibitor-induced apoptosis in colon cancer cells.
AB  - Inhibitors of histone deacetylases (HDAC) inhibit malignant cell growth and
      induce apoptosis through unknown mechanisms. Here, we report that the expression
      status of adenomatous polyposis coli (APC) protein determines the relative
      sensitivity of colon cancer cells to HDAC inhibitor-induced apoptosis. HCA-7
      cells (expressing wild-type beta-catenin and APC proteins) are more sensitive to
      apoptosis induced by HDAC inhibitors valproic acid (VPA) and suberoylanilide
      hydroxamic acid than SW620 or HT-29 cells (both expressing mutant APC). When wild
      type APC protein was expressed using an inducible expression system, HT-29 cells
      became sensitive to apoptosis in response to VPA. Conversely, knocking down of
      endogenous APC protein by small interfering RNA (siRNA) blocked VPA-induced
      apoptosis in HCA-7 cells. APC mediated VPA-induced apoptosis through down
      regulation of survivin. The level of survivin protein decreased in HCA-7 and HT
      29/APC cells, but not in SW620 and HT-29/beta-Gal cells after VPA treatment.
      Whereas knocking down of survivin by siRNA sensitized SW620 cells to VPA-induced
      apoptosis, overexpression of survivin blocked VPA-induced apoptosis in HCA-7
      cells. Down-regulation of survivin transcription occurred through changes in GSK
      3beta/beta-catenin/Tcf-4 signaling molecules. VPA also induced proteasome
      mediated degradation of survivin protein in HCA-7 cells. Furthermore, we have
      shown that APC mutation-mediated resistance to apoptosis can be overcome by
      cotreatment with Flavopiridol, which promotes survivin degradation. These results
      suggest that APC is a critical determinant of HDAC inhibitor-induced apoptosis in
      colon cancer cells and survivin is a potential target to enhance apoptotic
      response to HDAC inhibitors.

PMID- 16982770
TI  - Nelfinavir down-regulates hypoxia-inducible factor 1alpha and VEGF expression and
      increases tumor oxygenation: implications for radiotherapy.
AB  - The phosphatidylinositol 3-kinase (PI3K)/Akt pathway can increase vascular
      endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha)
      expression. We examined the effect of nelfinavir, an HIV protease inhibitor that
      inhibits Akt signaling, on VEGF and HIF-1alpha expression and on angiogenesis,
      tumor oxygenation, and radiosensitization. Nelfinavir decreases VEGF expression
      under normoxia via the transcription factor Sp1, which regulates the proximal
      core VEGF promoter. Nelfinavir decreased Sp1 phosphorylation and decreased Sp1
      binding to a probe corresponding to the proximal VEGF promoter in a gel shift
      assay. Nelfinavir also decreased the hypoxic induction of HIF-1alpha, which also
      regulates the VEGF promoter, most likely by decreasing its translation. The
      effect of nelfinavir on VEGF expression had the functional consequence of
      decreasing angiogenesis in an in vivo Matrigel plug assay. To determine the
      effect this might have on tumor radiosensitization, we did tumor regrowth assays
      with xenografts in nude mice. The combination of nelfinavir and radiation
      increased time to regrowth compared with radiation alone whereas nelfinavir alone
      had little effect on tumor regrowth. This radiosensitizing effect was greater
      than suggested by in vitro clonogenic survival assays. One possible explanation
      for the discordance is that nelfinavir has an effect on tumor oxygenation.
      Therefore, we examined this with the hypoxia marker EF5 and found that nelfinavir
      leads to increased oxygenation within tumor xenografts. Our results suggest that
      nelfinavir decreases HIF-1alpha/VEGF expression and tumor hypoxia, which could
      play a role in its in vivo radiosensitizing effect. These data support the use of
      nelfinavir in combination with radiation in future clinical trials.

PMID- 16982771
TI  - (-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death
      by targeting the molecular chaperone glucose-regulated protein 78.
AB  - Many beneficial properties have been attributed to (-)-epigallocatechin gallate
      (EGCG), including chemopreventive, anticarcinogenic, and antioxidant actions. In
      this study, we investigated the effects of EGCG on the function of glucose
      regulated protein 78 (GRP78), which is associated with the multidrug resistance
      phenotype of many types of cancer cells. Our investigation was directed at
      elucidating the mechanism of the EGCG and GRP78 interaction and providing
      evidence about whether EGCG modulates the activity of anticancer drugs through
      the inhibition of GRP78 function. We found that EGCG directly interacted with
      GRP78 at the ATP-binding site of protein and regulated its function by competing
      with ATP binding, resulting in the inhibition of ATPase activity. EGCG binding
      caused the conversion of GRP78 from its active monomer to the inactive dimer and
      oligomer forms. Further, we showed that EGCG interfered with the formation of the
      antiapoptotic GRP78-caspase-7 complex, which resulted in an increased etoposide
      induced apoptosis in cancer cells. We also showed that EGCG significantly
      suppressed the transformed phenotype of breast cancer cells treated with
      etoposide. Overall, these results strongly suggested that EGCG could prevent the
      antiapoptotic effect of GRP78, which usually suppresses the caspase-mediated cell
      death pathways in drug-treated cancer cells, contributing to the development of
      drug resistance.

PMID- 16982772
TI  - Combined depletion of cell cycle and transcriptional cyclin-dependent kinase
      activities induces apoptosis in cancer cells.
AB  - Selective cyclin-dependent kinase (cdk) 2 inhibition is readily compensated.
      However, reduced cdk2 activity may have antiproliferative effects in concert with
      other family members. Here, inducible RNA interference was used to codeplete cdk2
      and cdk1 from NCI-H1299 non-small cell lung cancer and U2OS osteosarcoma cells,
      and effects were compared with those mediated by depletion of either cdk alone.
      Depletion of cdk2 slowed G1 progression of NCI-H1299 cells and depletion of cdk1
      slowed G2-M progression in both cell lines, with associated endoreduplication in
      U2OS cells. However, compared with the incomplete cell cycle blocks produced by
      individual depletion, combined depletion had substantial consequences, with G2-M
      arrest predominating in NCI-H1299 cells and apoptosis the primary outcome in U2OS
      cells. In U2OS cells, combined depletion affected RNA polymerase II expression
      and phosphorylation, causing decreased expression of the antiapoptotic proteins
      Mcl-1 and X-linked inhibitor of apoptosis (XIAP), effects usually mediated by
      inhibition of the transcriptional cdk9. These events do not occur after
      individual depletion of cdk2 and cdk1, suggesting that reduction of cdk2, cdk1,
      and RNA polymerase II activities all contribute to apoptosis in U2OS cells. The
      limited cell death induced by combined depletion in NCI-H1299 cells was
      significantly increased by codepletion of cdk9 or XIAP or by simultaneous
      treatment with the cdk9 inhibitor flavopiridol. These results show the potency of
      concomitant compromise of cell cycle and transcriptional cdk activities and may
      guide the selection of clinical drug candidates.

PMID- 16982773
TI  - HLA class I antigen down-regulation in primary laryngeal squamous cell carcinoma
      lesions as a poor prognostic marker.
AB  - We have investigated the role of antigen-processing machinery (APM) component
      defects in HLA class I antigen down-regulation in laryngeal squamous cell
      carcinoma (SCC) lesions and assessed the clinical significance of these defects.
      To this end, 63 formalin-fixed, paraffin-embedded tumor lesions were examined for
      APM component and HLA class I antigen expression by immunohistochemistry.
      Calnexin, calreticulin, and ERp57 were down-regulated in approximately 25% of the
      lesions tested, whereas LMP2, TAP1, tapasin, and HLA class I antigens were down
      regulated in at least 70% of the lesions tested. LMP2 and tapasin expression was
      significantly correlated with HLA class I antigen expression suggesting APM
      component defects as a mechanism underlying HLA class I antigen down-regulation
      in laryngeal SCC lesions. The expression of most APM components and HLA class I
      antigens was correlated with the extent of CD8+ T cell infiltration into tumor
      lesions. Furthermore, LMP2 and HLA class I antigen down-regulation and low CD8+ T
      cell infiltration were significantly associated with reduced patients' survival.
      Multivariate analysis identified HLA class I antigen down-regulation as an
      independent unfavorable prognostic marker. This association is likely to reflect
      the reduction in the extent of CD8+ T cell infiltration in laryngeal SCC lesions.

PMID- 16982774
TI  - Human tumor-released microvesicles promote the differentiation of myeloid cells
      with transforming growth factor-beta-mediated suppressive activity on T
      lymphocytes.
AB  - Human tumors constitutively release endosome-derived microvesicles, transporting
      a broad array of biologically active molecules with potential modulatory effects
      on different immune cells. Here, we report the first evidence that tumor-released
      microvesicles alter myeloid cell function by impairing monocyte differentiation
      into dendritic cells and promoting the generation of a myeloid immunosuppressive
      cell subset. CD14+ monocytes isolated from healthy donors and differentiated with
      interleukin (IL)-4 and granulocyte macrophage colony-stimulating factor in the
      presence of tumor-derived microvesicles turned into HLA-DR(-/low) cells,
      retaining CD14 expression and failing to up-regulate costimulatory molecules,
      such as CD80 and CD86. These phenotypic changes were paralleled by a significant
      release of different cytokines, including IL-6, tumor necrosis factor-alpha, and
      transforming growth factor-beta (TGF-beta), and a dose-dependent suppressive
      activity on activated T-cell-proliferation and cytolytic functions, which could
      be reversed by anti-TGF-beta-neutralizing antibodies. Microvesicles isolated from
      plasma of advanced melanoma patients, but not from healthy donors, mediated
      comparable effects on CD14+ monocytes, skewing their differentiation toward
      CD14+HLA-DR-/low cells with TGF-beta-mediated suppressive activity on T-cell
      functions. Interestingly, a subset of TGF-beta-secreting CD14+HLA-DR- cells
      mediating suppressive activity on T lymphocytes was found to be significantly
      expanded in peripheral blood of melanoma patients compared with healthy donors.
      These data suggest the development in cancer patients of an immunosuppressive
      circuit by which tumors promote the generation of suppressive myeloid cells
      through the release of circulating microvesicles and without the need for cell-to
      cell contact. Therapeutic interventions on the crucial steps of this pathway may
      contribute to restore tumor/immune system interactions favoring T-cell-mediated
      control of tumor growth in cancer patients.

PMID- 16982776
TI  - Estrogen receptor positive breast cancer metastasis: altered hormonal sensitivity
      and tumor aggressiveness in lymphatic vessels and lymph nodes.
AB  - Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are
      estrogen receptor (ER) and/or progesterone receptor (PR) positive, then the
      likelihood that LN metastases express receptors exceeds 80%. However, due to lack
      of ER+ models, little is known about the role of hormones in breast cancer spread
      or the effects of the LN microenvironment on hormone responsiveness. We have
      developed metastasis models using ZsGreen labeled MCF-7 and T47D human breast
      cancer cells. Tumors are tracked in living mice by whole-body imaging, and
      macrometastases or micrometastases are detected by intravital imaging or
      fluorescence microscopy. Tumor growth is estrogen dependent and required for
      intratumoral lymphangiogenesis. Seventy-five percent of all tumors and >95% of
      larger tumors generate LN metastases. Occasionally more distant metastases are
      also observed. "Triads" of primary tumors, tumor-filled draining lymphatic
      vessels, and tumor-filled LNs from the same mouse show that (a) proliferation, as
      measured by 5-bromo-2'-deoxyuridine uptake, is higher in the LN than in the
      primary tumor. (b) High ER levels are extensively down-regulated by estradiol in
      primary tumors. However, there is partial failure of ER down-regulation in LNs
      associated with (c) reduced PR expression. This suggests that ER are
      dysfunctional in the LN microenvironment and perhaps hormone resistant. (d) CD44
      is sparsely expressed in primary tumor cells but homogeneously overexpressed in
      cells transiting the lymphatics and populating LNs. We hypothesize that CD44
      expression targets tumor cells for transport to, and uptake in, LNs. If so, the
      CD44 pathway could be targeted therapeutically to slow or prevent LN metastases.

PMID- 16982775
TI  - All-trans-retinoic acid improves differentiation of myeloid cells and immune
      response in cancer patients.
AB  - Abnormal dendritic cell differentiation and accumulation of immature myeloid
      suppressor cells (ImC) is one of the major mechanisms of tumor escape. We tested
      the possibility of pharmacologic regulation of myeloid cell differentiation using
      all-trans-retinoic acid (ATRA). Eighteen patients with metastatic renal cell
      carcinoma were treated with ATRA followed by s.c. interleukin 2 (IL-2). Eight
      healthy individuals comprised a control group. As expected, the cancer patients
      had substantially elevated levels of ImC. We observed that ATRA dramatically
      reduced the number of ImC. This effect was observed only in patients with high
      plasma concentration of ATRA (>150 ng/mL), but not in patients with lower ATRA
      concentrations (<135 ng/mL). Effects of ATRA on the proportions of different
      dendritic cell populations were minor. However, ATRA significantly improved
      myeloid/lymphoid dendritic cell ratio and the ability of patients' mononuclear
      cells to stimulate allogeneic T cells. This effect was associated with
      significant improvement of tetanus-toxoid-specific T-cell response. During the IL
      2 treatment, the ATRA effect was completely eliminated. To assess the role of IL
      2, specimens from 15 patients with metastatic renal cell carcinoma who had been
      treated with i.v. IL-2 alone were analyzed. In this group also, IL-2
      significantly reduced the number and function of dendritic cells as well as T
      cell function. These data indicate that ATRA at effective concentrations
      eliminated ImC, improved myeloid/lymphoid dendritic cell ratio, dendritic cell
      function, and antigen-specific T-cell response. ATRA treatment did not result in
      significant toxicity and it could be tested in therapeutic combination with
      cancer vaccines.

PMID- 16982777
TI  - The corepressor silencing mediator for retinoid and thyroid hormone receptor
      facilitates cellular recovery from DNA double-strand breaks.
AB  - Cells are frequently challenged by DNA double-strand breaks (DSB) that threaten
      their normal function and survival. In mammalian cells, the repair of DSBs is
      predominantly mediated by the DNA-dependent protein kinase (DNA-PK) complex. We
      unexpectedly found that the corepressor silencing mediator for retinoid and
      thyroid hormone receptor (SMRT) associates with the DNA-PK repair complex. The
      SMRT/histone deacetylase 3 complex is required for the transcriptional repressive
      property of the Ku70 subunit of the repair complex. Moreover, SMRT, but not the
      related Nuclear Receptor Corepressor, is required for cellular recovery from DNA
      DSBs induced by ionizing radiation or DNA damage-inducing drugs. Thus, the
      corepressor SMRT plays a novel and critical role in the cellular response to
      DSBs.

PMID- 16982778
TI  - Endogenous inhibition of histone deacetylase 1 by tumor-suppressive maspin.
AB  - Maspin, a noninhibitory serine protease inhibitor, exerts multifaceted tumor
      suppressive effects. Maspin expression is associated with better differentiated
      phenotypes, better cancer prognosis, and better drug sensitivity. Consistently,
      maspin also correlates with increased expression of Bax and p21WAF1/CIP1.
      Interestingly, histone deacetylase 1 (HDAC1), a major HDAC responsible for
      histone deacetylation, was shown to interact with maspin in a yeast two-hybrid
      screening. In this study, we confirmed the maspin/HDAC1 interaction in human
      prostate tissues, in prostate cancer cell lines, and with purified maspin. We
      produced several lines of evidence that support an inhibitory effect of maspin on
      HDAC1 through direct molecular interaction, which was detected in both the
      nucleus and the cytoplasm. Both endogenously expressed maspin and purified maspin
      inhibited HDAC1. In contrast, small interfering RNA (siRNA) silencing of maspin
      in PC3 cells increased HDAC activity. Accordingly, maspin-transfected DU145 cells
      exhibited increased expression of HDAC1 target genes Bax, cytokeratin 18 (CK18),
      and p21(WAF1/CIP1), whereas maspin siRNA decreased CK18 expression in PC3 cells.
      The maspin effect on HDAC1 correlated with an increased sensitivity to cytotoxic
      HDAC inhibitor M344. Interestingly, glutathione S-transferase (GST, another
      maspin partner) was detected in the maspin/HDAC1 complex. Furthermore, a COOH
      terminally truncated maspin mutant, which bound to HDAC1 but not GST, did not
      increase histone acetylation. Although HDACs, especially the highly expressed
      HDAC1, are promising therapeutic targets in cancer intervention, our data raise a
      novel hypothesis that the endogenous inhibitory effect of maspin on HDAC1 is
      coupled with glutathione-based protein modification, and provide new leads toward
      future developments of specific HDAC1-targeting strategies.

PMID- 16982779
TI  - Population-based study of natural variation in the melanocortin-1 receptor gene
      and melanoma.
AB  - Natural variation in the coding region of the melanocortin-1 receptor (MC1R) gene
      is associated with constitutive pigmentation phenotypes and development of
      melanoma and nonmelanoma skin cancers. We investigated the effect of MC1R
      variants on melanoma using a large, international population-based study design
      with complete determination of all MC1R coding region variants. Direct sequencing
      was completed for 2,202 subjects with a single primary melanoma (controls) and
      1,099 subjects with second or higher-order primary melanomas (cases) from
      Australia, the United States, Canada, and Italy. We observed 85 different MC1R
      variants, 10 of which occurred at a frequency >1%. Compared with controls, cases
      were more likely to carry two previously identified red hair ("R") variants
      [D84E, R151C, R160W, and D294H; odds ratio (OR), 1.6; 95% confidence interval
      (95% CI), 1.1-2.2]. This effect was similar among individuals carrying one R
      variant and one r variant (defined as any non-R MC1R variant; OR, 1.6; 95% CI,
      1.3-2.2) and among those carrying only one R variant (OR, 1.5; 95% CI, 1.1-1.9).
      There was no statistically significant association among those carrying only one
      or two r variants. Effects were similar across geographic regions and categories
      of pigmentation characteristics or number of moles. Our results confirm that MC1R
      is a low-penetrance susceptibility locus for melanoma, show that pigmentation
      characteristics may not modify the relationship of MC1R variants and melanoma
      risk, and suggest that associations may be smaller than previously reported in
      part due to the study design.

PMID- 16982780
TI  - In vitro activity of ceftobiprole against aerobic and anaerobic strains isolated
      from diabetic foot infections.
AB  - Against 443 aerobic and anaerobic bacteria isolated from diabetic foot
      infections, ceftobiprole MICs (microg/ml) at which 90% of the isolates tested
      were inhibited were as follows: methicillin-resistant Staphylococcus aureus, 1;
      methicillin-susceptible S. aureus and Staphylococcus lugdunensis, 0.5;
      Anaerococcus prevotii, 0.125; Finegoldia magna, 0.5; Peptoniphilus
      asaccharolyticus, 1; Peptostreptococcus anaerobius, 4; Escherichia coli and
      Enterobacter species, 0.125; Klebsiella species, 2; and Pseudomonas aeruginosa,
      8.

PMID- 16982781
TI  - In vitro human immunodeficiency virus type 1 resistance selections with
      combinations of tenofovir and emtricitabine or abacavir and lamivudine.
AB  - Human immunodeficiency virus type 1 (HIV-1) resistance development was evaluated
      in vitro by using combinations of the drugs tenofovir and emtricitabine or
      abacavir and lamivudine, as well as by using the compounds individually.
      Emtricitabine- and lamivudine-resistant HIV-1 isolates with the M184I or M184V
      mutation in reverse transcriptase were readily selected in the cultures with
      emtricitabine alone, lamivudine alone, and the two drug combinations and
      conferred high-level resistance to emtricitabine and lamivudine. Tenofovir
      resistant HIV-1 isolates with the K65R mutation occurred in both the culture with
      tenofovir alone and the culture with the combination of emtricitabine and
      tenofovir. The S68N and S68K mutations were also observed in the tenofovir
      cultures, with no detectable impact on resistance, suggesting a possible
      compensatory role in viral fitness. At low concentrations of emtricitabine and
      tenofovir, the M184I mutation appeared first, followed by the K65R mutation, in a
      subset of viruses. At intermediate concentrations of emtricitabine and tenofovir,
      viruses harboring the K65R mutation or a novel K65N and K70R double mutation grew
      before they gave rise to mutants with K65R and M184V/I double mutations at higher
      emtricitabine concentrations. Abacavir resistance was characterized by the
      accumulation of the M184V, Y115F, and K65R mutations in the abacavir culture,
      while the M184V and L74V mutations were selected in combination with lamivudine.
      In the presence of the abacavir resistance mutations, viral growth was strong
      even in the presence of high concentrations of abacavir. In contrast, viral
      growth was markedly impaired in the cultures with high tenofovir concentrations,
      even in the presence of K65R. In conclusion, these studies show that HIV-1
      mutants with a K65R and M184V genotype are generated under maximum selection
      pressure from the combination of tenofovir and emtricitabine.

PMID- 16982782
TI  - Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical
      patients.
AB  - Linezolid is a new antimicrobial agent effective against drug-resistant gram
      positive pathogens commonly responsible for central nervous system (CNS)
      infections in neurosurgical patients hospitalized in intensive care units. In
      order to study the penetration of this antimicrobial into the cerebrospinal fluid
      (CSF) of such patients, the disposition of linezolid in serum and CSF was studied
      in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h
      intravenous infusion) for the treatment of CNS infections caused by gram-positive
      pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state
      concentrations were analyzed by high-pressure liquid chromatography, and the
      concentration-time profiles obtained were analyzed to estimate pharmacokinetic
      parameters. The mean +/- standard deviation (SD) linezolid maximum and minimum
      measured concentrations were 18.6 +/- 9.6 microg/ml and 5.6 +/- 5.0 microg/ml,
      respectively, in serum and 10.8 +/- 5.7 microg/ml and 6.1 +/- 4.2 microg/ml,
      respectively, in CSF. The mean +/- SD areas under the concentration-time curves
      (AUCs) were 128.7 +/- 83.9 microg x h/ml for serum and 101.6 +/- 59.6 microg x
      h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for
      serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than
      that in serum (19.1 +/- 19.0 h and 6.5 +/- 3.6 h, respectively). The serum and
      CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4
      microg/ml for susceptible target pathogens for the entire dosing interval in the
      majority of patients. These findings suggest that linezolid may achieve adequate
      concentrations in the CSF of patients requiring antibiotics for the management or
      prophylaxis of CNS infections caused by gram-positive pathogens.

PMID- 16982783
TI  - Pharmacokinetics of itraconazole and hydroxyitraconazole in healthy subjects
      after single and multiple doses of a novel formulation.
AB  - Originally, itraconazole for parenteral administration was licensed in a 40%
      hydroxypropyl-beta-cyclodextrin (HPBCD) solution for intravenous administration.
      A novel formulation, the NanoCrystal formulation (NCF), was prepared. NCF
      consists of drug particles of approximately 200 to 300 nm. The pharmacokinetics
      of itraconazole and its hydroxy metabolite in healthy subjects were evaluated
      after single and multiple doses of itraconazole as NCF. In the single-ascending
      dose (SAD) study, itraconazole doses were planned to range from 50 to 500 mg,
      while in the multiple-ascending-dose (MAD) study, itraconazole doses of 100, 200,
      and 300 mg as NCF were studied, as was one dose level (200 mg) as an HBPCD
      solution. Samples were collected in heparinized tubes at various time points and
      were analyzed by high-performance liquid chromatography to allow full
      pharmacokinetic analysis both after the first dose and on day 7. The results of
      both the SAD and the MAD studies indicated that there was a dose dependency in
      the half-life of itraconazole from the novel formulation, increasing from 44 h
      (100 mg) to more than 150 h (300 mg) once steady state was achieved. Similar dose
      dependent effects were observed for the hydroxy metabolite. The areas under the
      concentration-time curves for itraconazole and hydroxyitraconazole were also dose
      dependent. The pharmacokinetic profiles after 200-mg doses of itraconazole as NCF
      and HPBCD formulations were comparable with respect to the terminal half-life,
      both after a single dose and at steady state. NCF may provide an alternative to
      the HPBCD solution for the further optimization of antifungal treatment with
      itraconazole.

PMID- 16982784
TI  - Role of Asp104 in the SHV beta-lactamase.
AB  - Among the TEM-type extended-spectrum beta-lactamases (ESBLs), an amino acid
      change at Ambler position 104 (Glu to Lys) results in increased resistance to
      ceftazidime and cefotaxime when found with other substitutions (e.g., Gly238Ser
      and Arg164Ser). To examine the role of Asp104 in SHV beta-lactamases, site
      saturation mutagenesis was performed. Our goal was to investigate the properties
      of amino acid residues at this position that affect resistance to penicillins and
      oxyimino-cephalosporins. Unexpectedly, 58% of amino acid variants at position 104
      in SHV expressed in Escherichia coli DH10B resulted in beta-lactamases with
      lowered resistance to ampicillin. In contrast, increased resistance to cefotaxime
      was demonstrated only for the Asp104Arg and Asp104Lys beta-lactamases. When all
      19 substitutions were introduced into the SHV-2 (Gly238Ser) ESBL, the most
      significant increases in cefotaxime and ceftazidime resistance were noted for
      both the doubly substituted Asp104Lys Gly238Ser and the doubly substituted
      Asp104Arg Gly238Ser beta-lactamases. Correspondingly, the overall catalytic
      efficiency (kcat/Km) of hydrolysis for cefotaxime was increased from 0.60 +/-
      0.07 microM(-1) s(-1) (mean +/- standard deviation) for Gly238Ser to 1.70 +/-
      0.01 microM(-1) s(-1) for the Asp104Lys and Gly238Ser beta-lactamase (threefold
      increase). We also showed that (i) k3 was the rate-limiting step for the
      hydrolysis of cefotaxime by Asp104Lys, (ii) the Km for cefotaxime of the doubly
      substituted Asp104Lys Gly238Ser variant approached that of the Gly238Ser beta
      lactamase as pH increased, and (iii) Lys at position 104 functions in an
      energetically additive manner with the Gly238Ser substitution to enhance
      catalysis of cephalothin. Based on this analysis, we propose that the amino acid
      at Ambler position 104 in SHV-1 beta-lactamase plays a major role in substrate
      binding and recognition of oxyimino-cephalosporins and influences the
      interactions of Tyr105 with penicillins.

PMID- 16982785
TI  - Urinary bactericidal activity of extended-release ciprofloxacin (1,000
      milligrams) versus levofloxacin (500 milligrams) in healthy volunteers receiving
      a single oral dose.
AB  - Twelve volunteers received a single oral dose of 1,000 mg extended-release (XR)
      ciprofloxacin versus 500 mg levofloxacin to assess urinary bactericidal titers
      (UBTs) against common uropathogens. Areas under UBT-time curves were
      significantly larger for Proteus mirabilis with XR ciprofloxacin and for
      staphylococci with levofloxacin.

PMID- 16982786
TI  - Antifungal effects on metabolite profiles of medically important yeast species
      measured by nuclear magnetic resonance spectroscopy.
AB  - Drug-induced inhibition of fungal growth is used in the diagnostic laboratory to
      predict therapeutic efficacy but is relatively slow, and determination of
      endpoints can be problematic. Nuclear magnetic resonance (NMR) spectroscopy
      identifies the metabolic complement of microorganisms while monitoring
      utilization of constituents of the incubation medium. This technique may provide
      a rapid and objective indicator of antifungal effects. We evaluated the effects
      of caspofungin, amphotericin B (AMB), and voriconazole on metabolic profiles of
      yeast species cultured in RPMI-2% glucose-morpholinepropanesulfonic acid buffer
      in microtiter plates in a proof-of-principle study. 1H NMR spectra were obtained
      using Bruker NMR spectrometers at 1H frequencies of 600 and 360 MHz. Metabolites
      were identified by two-dimensional correlation NMR spectra, and relative peak
      integrals were calculated from one-dimensional 1H NMR spectra. MICs were
      determined by a modification of the Clinical and Laboratory Standards Institute
      broth microdilution method M27-A. Utilization of glucose and branched-chain and
      aromatic amino acid substrates was accompanied by fungal production of acetate,
      acetaldehyde, ethanol, formate, fumarate, glycerol, lactate, pyruvate, and
      succinate. Clear-cut metabolic endpoints indicating a greater than 50% reduction
      in substrate utilization and fungal metabolite production which correlated with
      MICs were noted at 16 and 24 h for all three drugs. At 8 h, reductions of greater
      than 50% for selected metabolites were noted for caspofungin and AMB. Direct NMR
      based observation of metabolic alterations in yeast cultures reveals changes in
      key metabolic pathways and should be evaluated formally as a rapid technique for
      determining susceptibility to antifungal drugs.

PMID- 16982787
TI  - Prevalence of mutations associated with higher levels of sulfadoxine
      pyrimethamine resistance in Plasmodium falciparum isolates from Car Nicobar
      Island and Assam, India.
AB  - To assess sulfadoxine and pyrimethamine resistance (SPR), we describe here the
      dihydropteroate synthetase (DHPS) mutations among the Plasmodium falciparum
      isolates in which dihydrofolate reductase (DHFR) mutations had recently been
      described by us (A. Ahmed, M. K. Das, V. Dev, M. A. Saifi, Wajihullah, and Y. D.
      Sharma, Antimicrob. Agents Chemother. 50:1546-1549, 2006). A majority of isolates
      from Car Nicobar island showed double DHPS mutations, whereas a majority of
      isolates from Uttar Pradesh (U.P.) and Assam contained the wild-type DHPS. Based
      on DHFR-DHPS mutations, the expected level of SPR was lowest in U.P., higher in
      Assam, and highest in Car Nicobar, suggesting that a region-wise drug policy is
      needed in India.

PMID- 16982788
TI  - qnrA in CTX-M-producing Escherichia coli isolates from France.
AB  - By PCR, we screened for qnr genes 112 clinical isolates of extended-spectrum beta
      lactamase-producing Escherichia coli collected from hospitals in France during
      2004. For the first time, 7.7% of CTX-M-producing E. coli isolates presented a
      plasmid-mediated resistance to quinolones. All strains harbored a qnrA gene
      located on a sul1-type class 1 integron with similar structure to the In36
      integron.

PMID- 16982789
TI  - Duration of outpatient fecal colonization due to Escherichia coli Isolates with
      decreased susceptibility to fluoroquinolones: longitudinal study of patients
      recently discharged from the hospital.
AB  - Among 10 subjects colonized with Escherichia coli isolates with reduced
      susceptibility to fluoroquinolones, the median duration of colonization following
      hospital discharge was 80 days (range, 8 to 172 days). Colonization was longer
      for isolates demonstrating organic-solvent tolerance than for isolates that were
      not organic-solvent tolerant (151 versus 29 days, respectively; P = 0.07) but was
      not associated with other resistance mechanisms, demographics, or antibiotic use.

PMID- 16982790
TI  - Emergence of a novel lamivudine-resistant hepatitis B virus variant with a
      substitution outside the YMDD motif.
AB  - Lamivudine is a major drug approved for treatment of chronic hepatitis B virus
      (HBV) infection. Emergence of drug-resistant mutants with amino acid
      substitutions in the YMDD motif is a well-documented problem during long-term
      lamivudine therapy. Here we report a novel lamivudine-resistant strain of HBV
      with an intact YMDD motif, which included an amino acid substitution, rtA181T, in
      the reverse transcriptase (RT) domain of HBV polymerase. The substitution also
      induced a unique amino acid substitution (W172L) in the overlapping hepatitis B
      surface (HBs) protein. The YMDD mutant strains were not detected even by using
      the sensitive peptide nucleic acid-mediated PCR clamping method. The detected
      nucleotide substitution was accompanied by the emergence of an additional
      nucleotide substitution that induced amino acid change (S331C) in the spacer
      domain. The rtA181T mutant strain displayed a threefold decrease in
      susceptibility to lamivudine in in vitro experiments in comparison with the wild
      type. In vivo analysis using human hepatocyte-chimeric mice confirmed the
      resistance of this mutant strain to lamivudine. We developed a method to detect
      this novel rtA181T mutation and a previously reported rtA181T mutation with the
      HBs stop codon using restriction fragment length polymorphism PCR and identified
      one patient with the latter pattern among 40 patients with lamivudine resistance.
      In conclusion, although the incidence is not high, we have to be careful
      regarding the emergence of lamivudine-resistant mutant strains with intact YMDD
      motif.

PMID- 16982791
TI  - Rapid emergence of resistance to linezolid during linezolid therapy of an
      Enterococcus faecium infection.
AB  - We report the emergence of linezolid resistance (MICs of 16 to 32 mg/liter) in
      clonally related vancomycin-susceptible and -resistant Enterococcus faecium
      isolates from an intensive care unit patient after 12 days of linezolid therapy.
      Only linezolid-susceptible isolates of the same clone were detected at 28 days
      after termination of linezolid therapy.

PMID- 16982792
TI  - Prevalence and genetic analysis of plasmid-mediated quinolone resistance
      determinants QnrA and QnrS in Enterobacteriaceae isolates from a French
      university hospital.
AB  - The spread of plasmid-mediated quinolone resistance determinants QnrA and QnrS
      was evaluated in a collection of 186 extended-spectrum beta-lactamase (ESBL)
      positive enterobacterial isolates from 2002 to 2005 and 185 nalidixic acid
      resistant strains isolated during the first 6 months of 2005 at the Bicetre
      hospital, France. Out of these 186 ESBL-positive isolates, 2.2 and 1.6% carried a
      QnrA1 and a QnrS1 determinant, respectively. The ESBLs associated with QnrA1 were
      VEB-1, SHV-12, and CTX-M-1, whereas those associated with QnrS1 were TEM-52, SHV
      12, and CTX-M-1. Among the 185 nalidixic acid-resistant strains isolated in 2005,
      0.5 and 2.7% had a QnrA1 determinant and a QnrS1 determinant, respectively. The
      genetic environments of the qnrA1 gene differed but were always associated with
      sul1 type integrons. In contrast, qnrS1 genes were not embedded in class 1
      integrons but located often (but not systematically) downstream of the insertion
      sequence ISEcl2 on plasmids that often carried a novel beta-lactamase gene,
      bla(LAP-1). This is the first study identifying the QnrS resistance determinant
      in Europe and indicating that this determinant might also be widespread.

PMID- 16982793
TI  - Genetic environment of acquired bla(ACC-1) beta-lactamase gene in
      Enterobacteriaceae isolates.
AB  - We studied the genetic organization of bla(ACC-1) in 14 isolates of
      Enterobacteriaceae from France, Tunisia, and Germany. In a common ancestor,
      ISEcp1 was likely involved in the mobilization of this gene from the Hafnia alvei
      chromosome to a plasmid. Other genetic events involving insertion sequences
      (particularly IS26), transposons (particularly Tn1696), or sulI-type integrons
      have occurred, leading to complex genetic environments.

PMID- 16982794
TI  - Mutations in the E9L polymerase gene of cidofovir-resistant vaccinia virus strain
      WR are associated with the drug resistance phenotype.
AB  - Cidofovir (CDV) is an effective drug against viruses of the Orthopoxviridae
      family and is active in vitro against variola virus, the cause of smallpox.
      However, CDV-resistant poxviruses can be generated by repeated in vitro passage
      in the presence of suboptimal concentrations of CDV. To determine if mutations in
      the E9L polymerase gene could confer resistance to this nucleoside analog, this
      gene was sequenced from CDV-resistant vaccinia virus and found to encode five
      amino acid changes, centered on an N-terminal region associated with 3'-->5'
      exonuclease activity. Transfer of this mutant E9L gene into wild-type vaccinia
      virus by marker rescue sufficed to confer the resistance phenotype. E9L
      polymerase mutations occurred sequentially during passage in CDV, and an
      H296Y/S338F double mutant that conferred an intermediate CDV resistance phenotype
      was identified. In vitro, the marker-rescued CDV-resistant vaccinia virus
      containing all five mutations grew nearly as well as wild-type vaccinia virus.
      However, the virulence of this virus for mice was reduced, as 10- to 30-fold more
      CDV-resistant virus than wild-type virus was required for lethality following
      intranasal challenge. Cidofovir and hexadecyloxypropyl-cidofovir gave partial
      protection to mice infected with the virus when used at 50 and 100 mg/kg of body
      weight given as single treatments 24 h after virus exposure, whereas 2-amino-7
      [(1,3-dihydroxy-2-propoxy)methyl]purine (compound S2242) was completely
      protective at 25, 50, and 100 mg/kg/day when given daily for 5 days. These
      findings suggest that drug therapy for poxviruses may be complicated by drug
      resistance but that treatment of the infection with currently known compounds is
      possible.

PMID- 16982795
TI  - Search for cyclodextrin-based inhibitors of anthrax toxins: synthesis, structural
      features, and relative activities.
AB  - Recently, using structure-inspired drug design, we demonstrated that aminoalkyl
      derivatives of beta-cyclodextrin inhibited anthrax lethal toxin action by
      blocking the transmembrane pore formed by the protective antigen (PA) subunit of
      the toxin. In the present study, we evaluate a series of new beta-cyclodextrin
      derivatives with the goal of identifying potent inhibitors of anthrax toxins.
      Newly synthesized hepta-6-thioaminoalkyl and hepta-6-thioguanidinoalkyl
      derivatives of beta-cyclodextrin with alkyl spacers of various lengths were
      tested for the ability to inhibit cytotoxicity of lethal toxin in cells as well
      as to block ion conductance through PA channels reconstituted in planar bilayer
      lipid membranes. Most of the tested derivatives were protective against anthrax
      lethal toxin action at low or submicromolar concentrations. They also blocked ion
      conductance through PA channels at concentrations as low as 0.1 nM. The
      activities of the derivatives in both cell protection and channel blocking were
      found to depend on the length and chemical nature of the substituent groups. One
      of the compounds was also shown to block the edema toxin activity. It is hoped
      that these results will help to identify a new class of drugs for anthrax
      treatment, i.e., drugs that block the pathway for toxin translocation into the
      cytosol, the PA channel.

PMID- 16982796
TI  - Thymidine kinase mutations conferring acyclovir resistance in herpes simplex type
      1 recombinant viruses.
AB  - Contributions of thymidine kinase (TK) mutations to acyclovir (ACV) resistance
      were evaluated in herpes simplex virus type 1 recombinant viruses generated using
      a set of overlapping cosmids and plasmids. Alterations in both conserved and
      nonconserved regions of the TK gene were shown to confer high levels of
      resistance to ACV.

PMID- 16982797
TI  - Heparanase deglycanation of syndecan-1 is required for binding of the epithelial
      restricted prosecretory mitogen lacritin.
AB  - Cell surface heparan sulfate (HS) proteoglycans are carbohydrate-rich regulators
      of cell migratory, mitogenic, secretory, and inflammatory activity that bind and
      present soluble heparin-binding growth factors (e.g., fibroblast growth factor,
      Wnt, Hh, transforming growth factor beta, amphiregulin, and hepatocyte growth
      factor) to their respective signaling receptors. We demonstrate that the
      deglycanated core protein of syndecan-1 (SDC1) and not HS chains nor SDC2 or -4,
      appears to target the epithelial selective prosecretory mitogen lacritin. An
      important and novel step in this mechanism is that binding necessitates prior
      partial or complete removal of HS chains by endogenous heparanase. This limits
      lacritin activity to sites where heparanase appears to predominate, such as sites
      of exocrine cell migration, secretion, renewal, and inflammation. Binding is
      mutually specified by lacritin's C-terminal mitogenic domain and SDC1's N
      terminus. Heparanase modification of the latter transforms a widely expressed HS
      proteoglycan into a highly selective surface-binding protein. This novel example
      of cell specification through extracellular modification of an HS proteoglycan
      has broad implications in development, homeostasis, and disease.

PMID- 16982798
TI  - Higher order Rab programming in phagolysosome biogenesis.
AB  - Phagosomes offer kinetically and morphologically tractable organelles to dissect
      the control of phagolysosome biogenesis by Rab GTPases. Model phagosomes
      harboring latex beads undergo a coordinated Rab5-Rab7 exchange, which is akin to
      the process of endosomal Rab conversion, the control mechanisms of which are
      unknown. In the process of blocking phagosomal maturation, the intracellular
      pathogen Mycobacterium tuberculosis prevents Rab7 acquisition, thus, providing a
      naturally occurring tool to study Rab conversion. We show that M. tuberculosis
      inhibition of Rab7 acquisition and arrest of phagosomal maturation depends on
      Rab22a. Four-dimensional microscopy revealed that phagosomes harboring live
      mycobacteria recruited and retained increasing amounts of Rab22a. Rab22a
      knockdown in macrophages via siRNA enhanced the maturation of phagosomes with
      live mycobacteria. Conversely, overexpression of the GTP-locked mutant Rab22aQ64L
      prevented maturation of phagosomes containing heat-killed mycobacteria, which
      normally progress into phagolysosomes. Moreover, Rab22a knockdown led to Rab7
      acquisition by phagosomes harboring live mycobacteria. Our findings show that
      Rab22a defines the critical checkpoint for Rab7 conversion on phagosomes,
      allowing or disallowing organellar transition into a late endosomal compartment.
      M. tuberculosis parasitizes this process by actively recruiting and maintaining
      Rab22a on its phagosome, thus, preventing Rab7 acquisition and blocking
      phagolysosomal biogenesis.

PMID- 16982799
TI  - Structural and functional features and significance of the physical linkage
      between ER and mitochondria.
AB  - The role of mitochondria in cell metabolism and survival is controlled by calcium
      signals that are commonly transmitted at the close associations between
      mitochondria and endoplasmic reticulum (ER). However, the physical linkage of the
      ER-mitochondria interface and its relevance for cell function remains elusive. We
      show by electron tomography that ER and mitochondria are adjoined by tethers that
      are approximately 10 nm at the smooth ER and approximately 25 nm at the rough ER.
      Limited proteolysis separates ER from mitochondria, whereas expression of a short
      "synthetic linker" (<5 nm) leads to tightening of the associations. Although
      normal connections are necessary and sufficient for proper propagation of ER
      derived calcium signals to the mitochondria, tightened connections, synthetic or
      naturally observed under apoptosis-inducing conditions, make mitochondria prone
      to Ca2+ overloading and ensuing permeability transition. These results reveal an
      unexpected dependence of cell function and survival on the maintenance of proper
      spacing between the ER and mitochondria.

PMID- 16982800
TI  - Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein
      vMIA.
AB  - Replication of human cytomegalovirus (CMV) requires the expression of the viral
      mitochondria-localized inhibitor of apoptosis (vMIA). vMIA inhibits apoptosis by
      recruiting Bax to mitochondria, resulting in its neutralization. We show that
      vMIA decreases cell size, reduces actin polymerization, and induces cell
      rounding. As compared with vMIA-expressing CMV, vMIA-deficient CMV, which
      replicates in fibroblasts expressing the adenoviral apoptosis suppressor E1B19K,
      induces less cytopathic effects. These vMIA effects can be separated from its
      cell death-inhibitory function because vMIA modulates cellular morphology in Bax
      deficient cells. Expression of vMIA coincided with a reduction in the cellular
      adenosine triphosphate (ATP) level. vMIA selectively inhibited one component of
      the ATP synthasome, namely, the mitochondrial phosphate carrier. Exposure of
      cells to inhibitors of oxidative phosphorylation produced similar effects, such
      as an ATP level reduced by 30%, smaller cell size, and deficient actin
      polymerization. Similarly, knockdown of the phosphate carrier reduced cell size.
      Our data suggest that the cytopathic effect of CMV can be explained by vMIA
      effects on mitochondrial bioenergetics.

PMID- 16982801
TI  - Ca2+ and synaptotagmin VII-dependent delivery of lysosomal membrane to nascent
      phagosomes.
AB  - Synaptotagmin (Syt) VII is a ubiquitously expressed member of the Syt family of
      Ca2+ sensors. It is present on lysosomes in several cell types, where it
      regulates Ca2+-dependent exocytosis. Because [Ca2+]i and exocytosis have been
      associated with phagocytosis, we investigated the phagocytic ability of
      macrophages from Syt VII-/- mice. Syt VII-/- macrophages phagocytose normally at
      low particle/cell ratios but show a progressive inhibition in particle uptake
      under high load conditions. Complementation with Syt VII rescues this phenotype,
      but only when functional Ca2+-binding sites are retained. Reinforcing a role for
      Syt VII in Ca2+-dependent phagocytosis, particle uptake in Syt VII-/- macrophages
      is significantly less dependent on [Ca2+]i. Syt VII is concentrated on peripheral
      domains of lysosomal compartments, from where it is recruited to nascent
      phagosomes. Syt VII recruitment is rapidly followed by the delivery of Lamp1 to
      phagosomes, a process that is inhibited in Syt VII-/- macrophages. Thus, Syt VII
      regulates the Ca2+-dependent mobilization of lysosomes as a supplemental source
      of membrane during phagocytosis.

PMID- 16982802
TI  - p120 catenin is essential for mesenchymal cadherin-mediated regulation of cell
      motility and invasiveness.
AB  - During epithelial tumor progression, the loss of E-cadherin expression and
      inappropriate expression of mesenchymal cadherins coincide with increased
      invasiveness. Reexpression experiments have established E-cadherin as an invasion
      suppressor. However, the mechanism by which E-cadherin suppresses invasiveness
      and the role of mesenchymal cadherins are poorly understood. We show that both
      p120 catenin and mesenchymal cadherins are required for the invasiveness of E
      cadherin-deficient cells. p120 binding promotes the up-regulation of mesenchymal
      cadherins and the activation of Rac1, which are essential for cell migration and
      invasiveness. p120 also promotes invasiveness by inhibiting RhoA activity,
      independently of cadherin association. Furthermore, association of endogenous
      p120 with E-cadherin is required for E-cadherin-mediated suppression of
      invasiveness and is accompanied by a reduction in mesenchymal cadherin levels.
      The data indicate that p120 acts as a rheostat, promoting a sessile cellular
      phenotype when associated with E-cadherin or a motile phenotype when associated
      with mesenchymal cadherins.

PMID- 16982803
TI  - Nuclear import time and transport efficiency depend on importin beta
      concentration.
AB  - Although many components and reaction steps necessary for bidirectional transport
      across the nuclear envelope (NE) have been characterized, the mechanism and
      control of cargo migration through nuclear pore complexes (NPCs) remain poorly
      understood. Single-molecule fluorescence microscopy was used to track the
      movement of cargos before, during, and after their interactions with NPCs. At low
      importin beta concentrations, about half of the signal-dependent cargos that
      interacted with an NPC were translocated across the NE, indicating a nuclear
      import efficiency of approximately 50%. At high importin beta concentrations, the
      import efficiency increased to approximately 80% and the transit speed increased
      approximately sevenfold. The transit speed and import efficiency of a signal
      independent cargo was also increased by high importin beta concentrations. These
      results demonstrate that maximum nucleocytoplasmic transport velocities can be
      modulated by at least approximately 10-fold by the importin beta concentration
      and therefore suggest a potential mechanism for regulating the speed of cargo
      traffic across the NE.

PMID- 16982804
TI  - HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward
      endothelial cells.
AB  - Reendothelialization involves endothelial progenitor cell (EPC) homing,
      proliferation, and differentiation, which may be influenced by fluid shear stress
      and local flow pattern. This study aims to elucidate the role of laminar flow on
      embryonic stem (ES) cell differentiation and the underlying mechanism. We
      demonstrated that laminar flow enhanced ES cell-derived progenitor cell
      proliferation and differentiation into endothelial cells (ECs). Laminar flow
      stabilized and activated histone deacetylase 3 (HDAC3) through the Flk-1-PI3K-Akt
      pathway, which in turn deacetylated p53, leading to p21 activation. A similar
      signal pathway was detected in vascular endothelial growth factor-induced EC
      differentiation. HDAC3 and p21 were detected in blood vessels during
      embryogenesis. Local transfer of ES cell-derived EPC incorporated into injured
      femoral artery and reduced neointima formation in a mouse model. These data
      suggest that shear stress is a key regulator for stem cell differentiation into
      EC, especially in EPC differentiation, which can be used for vascular repair, and
      that the Flk-1-PI3K-Akt-HDAC3-p53-p21 pathway is crucial in such a process.

PMID- 16982805
TI  - Sensitivity and specificity of various tests for the diagnosis of Helicobacter
      pylori in Egyptian children.
AB  - OBJECTIVES: Many noninvasive methods (using breath, blood, and stool samples) are
      available to diagnose Helicobacter pylori. However, because the noninvasive tests
      are proxy measures of the infection, they need validation before use. Factors
      that may affect test validity include patient age, gender, and geographic
      location. Because no data were available on the validation of noninvasive tests
      for the diagnosis of H. pylori among children in the Middle East, this study was
      performed. METHODS: Children between 2 and 17 years of age evaluated at the Cairo
      University School of Medicine pediatric gastroenterology clinic who were already
      scheduled for upper endoscopy were eligible for enrollment in the study. At the
      time of endoscopy, 3 biopsies were collected and used for rapid urease,
      histology, and culture, respectively. All children also donated a sample of stool
      and blood and had a urea breath test performed. Stool and serum samples were
      tested for the presence of H. pylori by using commercially available enzyme
      linked immunosorbent assay-based technology. The sensitivity, specificity, and
      positive and negative predictive values were calculated for each noninvasive test
      used in the study. Receiver operating curves also were charted to determine
      optimal cut points for the various tests when used in the current study cohort.
      RESULTS: One hundred eight children were enrolled in the study, with 52 children
      being under 6 years of age. The urea breath test and HpStar (DakoCytomation,
      Norden, Denmark) stool enzyme-linked immunosorbent assay kit had the highest
      sensitivity and specificity (sensitivity and specificity: 98 and 89 [urea breath
      test] and 94 and 81 [HpStar], respectively), whereas the serologic kit had an
      unacceptably low sensitivity (50%). The sensitivity of neither the urea breath
      test nor the HpStar tests was affected by subject age, but specificity of the
      HpStar test, although still high, was significantly lower among children under 6
      years. Receiver operating curves found optimal cut points of the urea breath test
      at 6.2 delta over baseline and of the HpStar at 0.25 enzyme-linked immunosorbent
      assay units. CONCLUSION: The urea breath test and HpSTAR stool antigen kit are
      reliable tests for the noninvasive diagnosis of H. pylori among children living
      in the Middle East.

PMID- 16982806
TI  - Expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral
      outcomes in Prader-Willi syndrome.
AB  - Prader-Willi syndrome is a neurodevelopmental disorder that is characterized by
      infantile hypotonia, feeding difficulties, hypogonadism, mental deficiency,
      hyperphagia (leading to obesity in early childhood), learning problems, and
      behavioral difficulties. A paternal 15q11-q13 deletion is found in approximately
      70% of patients with Prader-Willi syndrome, approximately 25% have uniparental
      maternal disomy 15, and the remaining 2% to 5% have imprinting defects. The
      proximal deletion breakpoint in the 15q11-q13 region occurs at 1 of 2 sites
      located within either of 2 large duplicons allowing for the identification of 2
      deletion subgroups. The larger, type I (TI) deletion involves breakpoint 1, which
      is close to the centromere, whereas the smaller, type II (TII) deletion involves
      breakpoint 2, located approximately 500 kilobases distal to breakpoint 1.
      Breakpoint 3 is located at the distal end of the 15q11-q13 region and common to
      both typical deletion subgroups. Analyses of the genetic subtypes of Prader-Willi
      syndrome to date have primarily compared individuals with typical deletion and
      uniparental maternal disomy 15 without grouping the individuals with a deletion
      into TI or TII. Distinct differences have been reported between individuals with
      Prader-Willi syndrome resulting from deletion compared with uniparental maternal
      disomy 15 in physical, cognitive, and behavioral parameters. We previously
      presented the first assessment of clinical differences in individuals with Prader
      Willi syndrome categorized as having type I or II deletions. Adaptive behavior,
      obsessive-compulsive behaviors, reading, math, and visual-motor integration
      assessments were generally poorer in individuals with Prader-Willi syndrome and
      the TI deletion compared with subjects with Prader-Willi syndrome with the TII
      deletion or uniparental maternal disomy 15. Four genes (NIPA1, NIPA2, CYFIP1, and
      GCP5) have been identified in the chromosomal region between breakpoints 1 and 2
      and are implicated in compulsive behavior and lower intellectual ability observed
      in individuals with Prader-Willi syndrome with TI versus TII deletions. We
      quantified messenger-RNA levels of these 4 genes in actively growing
      lymphoblastoid cells derived from 8 subjects with Prader-Willi syndrome with the
      TI deletion (4 males, 4 females; mean: age 25.2 +/- 8.9 years) and 9 with the TII
      deletion (3 males, 6 females; mean age: 19.5 +/- 5.8 years). Messenger-RNA levels
      were correlated with validated psychological and behavioral scales administered
      by trained psychologists blinded to genotype status. Messenger RNA from NIPA1,
      NIPA2, CYFIP1, and GCP5 was reduced but detectable in the subjects with Prader
      Willi syndrome with the TI deletion, supporting biallelic expression. For the
      most part, messenger-RNA values were positively correlated with assessment
      parameters, indicating a direct relationship between messenger-RNA levels and
      better assessment scores, with the highest correlation for NIPA2. The coefficient
      of determination indicated the quantity of messenger RNA of the 4 genes explained
      from 24% to 99% of the variation of the behavioral and academic parameters
      measured. By comparison, the coefficient of determination for deletion type alone
      explained 5% to 50% of the variation in the assessed parameters. Understanding
      the influence of gene expression on behavioral and cognitive characteristics in
      humans is in the early stage of research development. Additional research is
      needed to identify the function of these genes and their interaction with gene
      networks to clarify the potential role they play in central nervous system
      development and function.

PMID- 16982807
TI  - Antifungal prophylaxis to prevent neonatal candidiasis: a survey of perinatal
      physician practices.
AB  - BACKGROUND: Bloodstream infections with Candida species have a high mortality
      rate in very low birth weight infants. Preliminary data suggest that prophylaxis
      with fluconazole reduces the incidence of colonization and invasive Candida
      infections in high-risk, very low birth weight neonates. The extent of antifungal
      prophylaxis use to prevent neonatal candidemia is unknown. METHODS: We surveyed a
      20% random sample of the members of the American Academy of Pediatrics Section on
      Perinatal Pediatrics. We collected information on prophylactic agents used,
      indications for use, and rationale for reported practices. RESULTS: A total of
      219 (47%) of 469 members sampled responded; 3 clinicians who did not provide care
      to very low birth weight infants were excluded. Antifungal prophylaxis use was
      reported by 73 (34%) respondents. Agents used included intravenous fluconazole
      (66%), oral nystatin (59%), and intravenous amphotericin B (21%). Decreased birth
      weight or early gestational age was the most frequent indication to start
      prophylaxis (57 [78%]). Respondents who did not use antifungal prophylaxis
      compared with respondents who used fluconazole prophylaxis were significantly
      more likely to have concerns about (1) the emergence of antifungal resistance,
      (2) unclear criteria on which to base the decision to start prophylaxis, and (3)
      the need for clarification of the role of surveillance cultures. CONCLUSIONS:
      Although preliminary data suggest that fluconazole is efficacious to prevent
      candidemia in a subset of neonates, this practice is not used widely by
      clinicians who care for very low birth weight infants. Additional efficacy
      studies should address the emergence of antifungal resistance or clarification of
      criteria to initiate prophylaxis, including the role of surveillance cultures.

PMID- 16982808
TI  - Spontaneous hemopneumothorax in children: case report and review of literature.
AB  - Spontaneous hemopneumothorax is rare, occurs in young adolescents, and can be
      life threatening secondary to massive bleeding. An adolescent with spontaneous
      hemopneumothorax and shock managed by tube thorascostomy is described here. We
      compared our case with published data of spontaneous hemopneumothorax in the
      pediatric age group. Spontaneous hemopneumothorax involves the accumulation of
      air and blood in the pleural space in the absence of trauma or other obvious
      causes. Spontaneous hemopneumothorax is usually seen in adolescents, more common
      in males than females. The common clinical features of spontaneous
      hemopneumothorax include dyspnoea and chest pain, and 30% present with
      hypovolemic shock. The bleeding can result from a torn adhesion between the
      parietal and visceral pleurae, from a rupture of vascularized bullae, or from
      torn congenital aberrant vessels. Over the last 6 decades, the treatment has
      progressed from the thoracotomy to minimally invasive techniques such as video
      assisted thoracoscopic surgery, with great reduction in mortality and recurrence
      rates. Although a rare entity, diagnosis of spontaneous hemopneumothorax must be
      considered in young adolescents presenting with spontaneous onset of chest pain
      and dyspnoea with radiograph findings of hydropneumothorax and/or signs of shock.

PMID- 16982809
TI  - PPARgamma controls CD1d expression by turning on retinoic acid synthesis in
      developing human dendritic cells.
AB  - Dendritic cells (DCs) expressing CD1d, a molecule responsible for lipid antigen
      presentation, are capable of enhancing natural killer T (iNKT) cell
      proliferation. The signals controlling CD1 expression and lipid antigen
      presentation are poorly defined. We have shown previously that stimulation of the
      lipid-activated transcription factor, peroxisome proliferator-activated receptor
      (PPAR)gamma, indirectly regulates CD1d expression. Here we demonstrate that
      PPARgamma, turns on retinoic acid synthesis by inducing the expression of retinol
      and retinal metabolizing enzymes such as retinol dehydrogenase 10 and
      retinaldehyde dehydrogenase type 2 (RALDH2). PPARgamma-regulated expression of
      these enzymes leads to an increase in the intracellular generation of all-trans
      retinoic acid (ATRA) from retinol. ATRA regulates gene expression via the
      activation of the retinoic acid receptor (RAR)alpha in human DCs, and RARalpha
      acutely regulates CD1d expression. The retinoic acid-induced elevated expression
      of CD1d is coupled to enhanced iNKT cell activation. Furthermore, in vivo
      relevant lipids such as oxidized low-density lipoprotein can also elicit retinoid
      signaling leading to CD1d up-regulation. These data show that regulation of
      retinoid metabolism and signaling is part of the PPARgamma-controlled
      transcriptional events in DCs. The uncovered mechanisms allow the DCs to respond
      to altered lipid homeostasis by changing CD1 gene expression.

PMID- 16982811
TI  - Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively
      enhance expression of antimicrobial peptides.
AB  - Th17 cells are a distinct lineage of effector CD4(+) T cells characterized by
      their production of interleukin (IL)-17. We demonstrate that Th17 cells also
      expressed IL-22, an IL-10 family member, at substantially higher amounts than T
      helper (Th)1 or Th2 cells. Similar to IL-17A, IL-22 expression was initiated by
      transforming growth factor beta signaling in the context of IL-6 and other
      proinflammatory cytokines. The subsequent expansion of IL-22-producing cells was
      dependent on IL-23. We further demonstrate that IL-22 was coexpressed in vitro
      and in vivo with both IL-17A and IL-17F. To study a functional relationship among
      these cytokines, we examined the expression of antimicrobial peptides by primary
      keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F. IL-22 in
      conjunction with IL-17A or IL-17F synergistically induced the expression of beta
      defensin 2 and S100A9 and additively enhanced the expression of S100A7 and
      S100A8. Collectively, we have identified IL-22 as a new cytokine expressed by
      Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated
      with skin innate immunity.

PMID- 16982810
TI  - Impaired selection of invariant natural killer T cells in diverse mouse models of
      glycosphingolipid lysosomal storage diseases.
AB  - Glycolipid ligands for invariant natural killer T cells (iNKT cells) are loaded
      onto CD1d molecules in the late endosome/lysosome. Accumulation of
      glycosphingolipids (GSLs) in lysosomal storage diseases could potentially
      influence endogenous and exogenous lipid loading and/or presentation and, thus,
      affect iNKT cell selection or function. The percentages and frequency of iNKT
      cells were reduced in multiple mouse models of lysosomal GSL storage disease,
      irrespective of the specific genetic defect or lipid species stored. Reduced
      numbers of iNKT cells resulted in the absence of cytokine production in response
      to alpha-galactosylceramide (alpha-GalCer) and reduced iNKT cell-mediated lysis
      of wild-type targets loaded with alpha-GalCer. The reduction in iNKT cells did
      not result from defective expression of CD1d or a lack of antigen-presenting
      cells. Although H-2 restricted CD4(+) T cell responses were generally unaffected,
      processing of a lysosome-dependent analogue of alpha-GalCer was impaired in all
      the strains of mice tested. These data suggest that GSL storage may result in
      alterations in thymic selection of iNKT cells caused by impaired presentation of
      selecting ligands.

PMID- 16982812
TI  - Clonal origin of metastatic testicular teratomas.
AB  - PURPOSE: Testicular teratomas in adult patients are histologically diverse tumors
      that frequently coexist with other germ cell tumor (GCT) components. These mixed
      GCTs often metastasize to retroperitoneal lymph nodes where multiple GCT elements
      are frequently present in the same metastatic lesion. Neither the genetic
      relationships among the different components in metastatic lesions nor the
      relationships between primary and metastatic GCT components have been elucidated.
      EXPERIMENTAL DESIGN: We examined metastases from 31 patients who underwent
      primary retroperitoneal lymph node dissection for metastatic testicular GCT. All
      patients had metastatic mature teratoma with one or more other GCT components.
      This study included a total of 72 metastatic GCT components and 16 primary GCT
      components from 31 patients. Genomic DNA samples from each component were
      prepared from formalin-fixed, paraffin-embedded tissue sections using laser
      assisted microdissection. Loss of heterozygosity (LOH) assays for seven
      microsatellite polymorphic markers on chromosomes 1p36 (D1S1646), 9p21 (D9S171
      and IFNA), 9q21 (D9S303), 13q22-q31 (D13S317), 18q22 (D18S543), and 18q21
      (D18S60) were done to assess clonality. RESULTS: Twenty-nine of 31 (94%) cases
      showed allelic loss in one or more components of the metastatic GCTs. Twenty-nine
      of 31 mature teratomas showed allelic loss in at least one of seven
      microsatellite polymorphic markers analyzed. The frequency of allelic loss in
      informative cases of metastatic mature teratoma was 27% (8 of 30) with D1S1646,
      34% (10 of 29) with D9S171, 37% (10 of 27) with IFNA, 27% (8 of 30) with D9S303,
      46% (13 of 28) with D13S317, 26% (7 of 27) with D18S543, and 36% (10 of 28) with
      D18S60. Completely concordant allelic loss patterns between the mature teratoma
      and all of the other metastatic GCT components were seen in 26 of 29 cases in
      which the mature teratoma component showed LOH. Nearly identical allelic loss
      patterns were seen in the three remaining cases. In six cases analyzed, LOH
      patterns of each metastatic component were compared with each GCT component of
      the primary testicular tumor. In all six cases, each primary and metastatic
      component showed an identical pattern of allelic loss. CONCLUSION: Our data
      support the common clonal origin of metastatic mature teratomas with other
      components of metastatic testicular GCTs and with each component of the primary
      tumor.

PMID- 16982813
TI  - Calf muscles imaged at BOLD MR: correlation with TcPO2 and flowmetry measurements
      during ischemia and reactive hyperemia--initial experience.
AB  - PURPOSE: To prospectively compare the blood oxygen level-dependent (BOLD)
      magnetic resonance (MR) signal intensity of calf muscle during ischemia and
      reactive hyperemia with laser Doppler flowmetry (LDF) and transcutaneous oxygen
      pressure (TcPo2) measurements, two parameters routinely used to evaluate
      peripheral arterial occlusive disease. MATERIALS AND METHODS: The study was
      institutional review board approved; all volunteers gave informed consent.
      Fifteen healthy volunteers (eight male, seven female; mean age, 33.0 years +/-
      6.1 [standard deviation]) underwent LDF, TcPo2 measurement, and BOLD MR imaging
      of the calf during ischemia and reactive hyperemia. The BOLD signal intensity of
      the gastrocnemius muscle was measured at 1.5-T single-shot multiecho gradient
      echo echo-planar imaging. Time to half ischemia minimum (THIM), time to half
      hyperemia peak (THHP), and time to peak (TTP) after cuff deflation were measured
      with each method. Correlation coefficients (CCs) for associations of BOLD
      response with LDF and TcPo2 time courses were calculated. Student t testing of
      key BOLD MR, LDF, and TcPo2 measurement parameters was performed. RESULTS: During
      ischemia, normalized LDF and TcPo2 measurements decreased similarly to BOLD MR
      signal intensity (CCs: 0.86 and 0.96 for associations with LDF and TcPo2
      measurements, respectively). Mean THIM values were 136.0, 82.5, and 121.3 seconds
      for BOLD MR, LDF (P < .01), and TcPo2 (P > .05) measurements, respectively.
      During early reactive hyperemia, LDF and TcPo2 measurements increased rapidly to
      peak values, similarly to BOLD MR signal intensity (CCs: 0.81 and 0.78,
      respectively). Mean THHP values were 26.0, 12.5, and 44.0 seconds for BOLD MR,
      LDF (P < .01), and TcPo2 (P < .01) measurements, respectively. Mean TTP values
      were 48.7, 47.5, and 98.0 seconds for BOLD MR, LDF (P > .05), and TcPo2 (P < .01)
      measurements, respectively. CONCLUSION: BOLD MR imaging of calf muscles-depending
      on underlying key parameters-has moderate to good correlation with LDF and TcPo2
      measurements during ischemia and reactive hyperemia.

PMID- 16982814
TI  - Female pelvis: MR imaging at 3.0 T with sensitivity encoding and flip-angle sweep
      technique.
AB  - This study had institutional review board approval; all 33 patients (mean age, 47
      years +/- 16 [standard deviation]) gave informed consent. The aim was to
      prospectively evaluate the diagnostic image quality yielded by a 3.0-T T2
      weighted turbo spin-echo magnetic resonance imaging sequence with a very short
      imaging time versus that yielded by a standard 3.0-T sequence at imaging of the
      female pelvis. Signal-to-noise ratio and delineation of gynecologic disorders
      were approximately equal between the two sequences. The majority of tissue
      contrasts were comparable, but contrast between fluid and muscle was
      significantly higher and motion artifacts were reduced (P < .001 for both) with
      the short imaging time sequence. The fast sequence maintained or improved image
      quality and thus seems to be advantageous for uncooperative patients.

PMID- 16982815
TI  - Multidetector CT of pancreas: effects of contrast material flow rate and
      individualized scan delay on enhancement of pancreas and tumor contrast.
AB  - PURPOSE: To prospectively assess whether high contrast material flow rate (8
      mL/sec) and individualized scan delay improve enhancement of normal pancreas with
      multidetector computed tomography (CT) and, as a result, tumor-to-pancreas
      contrast of pancreatic adenocarcinoma. MATERIALS AND METHODS: Informed consent
      was obtained in 40 patients (21 women, 19 men; mean age, 67.1 years); the
      institutional review board approved this protocol. Patients were referred for
      multidetector CT because they were suspected of having a pancreatic tumor and
      were randomized to receive 150 mL of nonionic contrast material (300 mg of iodine
      per milliliter) at a flow rate of 4 mL/sec (n = 21) or 8 mL/sec (n = 19).
      Patients underwent dynamic scanning at one level every 2 seconds for 66 seconds
      after intravenous administration of contrast material. Contrast enhancement of
      pancreas and tumors was measured with circular regions of interest (analysis of
      variance and Bonferroni-Holm corrected post hoc t tests). RESULTS: Peak contrast
      enhancement in pancreas was observed significantly earlier (mean +/- standard
      deviation, 28.7 seconds +/- 3.5 vs 48.2 seconds +/- 5.3; P < .05) and was
      significantly higher (129.0 HU +/- 25.7 vs 106.2 HU +/- 35.4, P < .05) with a
      flow rate of 8 mL/sec than with a flow rate of 4 mL/sec. Tumor-to-pancreas
      contrast greater than 40 HU lasted significantly longer with a flow rate of 8
      mL/sec than with a flow rate of 4 mL/sec (26.4 seconds +/- 11.9 vs 8.6 seconds +/
      8.3, P < .05). With a flow rate of 8 mL/sec, an individualized scan delay of 19
      seconds after aortic transit time revealed higher tumor-to-pancreas contrast than
      did a fixed scan delay, and tumor conspicuity was better. CONCLUSION: With 16
      section CT, increased contrast material flow rate of 8 mL/sec and individualized
      scan delay were associated with improved pancreatic enhancement and tumor-to
      pancreas contrast compared with flow rate of 4 mL/sec and fixed scan delay.

PMID- 16982816
TI  - Screening for colorectal neoplasia with CT colonography: initial experience from
      the 1st year of coverage by third-party payers.
AB  - PURPOSE: To evaluate our experience in the 1st year of computed tomographic (CT)
      colonography screening since the initiation of local third-party payer coverage.
      MATERIALS AND METHODS: This HIPAA-compliant study was approved by the
      institutional review board, and informed consent was waived. Over a 1-year period
      that ended on April 27, 2005, 1110 consecutive adults (585 women, 525 men; mean
      age, 58.1 years) underwent primary CT colonography screening. More than 99% were
      covered by managed care agreements. CT colonographic interpretation was performed
      with primary three-dimensional polyp detection, and the final results were issued
      within 2 hours. Patients with large (> or =10-mm) polyps were referred for same
      day optical colonoscopy, and patients with medium-sized (6-9-mm) lesions had the
      option of immediate optical colonoscopy or short-term CT colonography
      surveillance. RESULTS: Large colorectal polyps were identified at CT colonography
      in 43 (3.9%) of 1110 patients. Medium-sized lesions were identified in 77 (6.9%)
      patients, 31 (40%) of whom chose optical colonoscopy and 46 (60%) of whom chose
      CT colonography surveillance. Concordant lesions were identified in 65 of 71
      patients who underwent subsequent optical colonoscopy (positive predictive value,
      91.5%). Sixty-one (86%) of 71 optical colonoscopic procedures were performed on
      the same day as CT colonography, thereby avoiding the need for repeat bowel
      preparation. The actual endoscopic referral rate for positive findings at CT
      colonography was 6.4% (71 of 1110 patients). The demand for CT colonography
      screening from primary care physicians and their patients increased throughout
      the study period. CONCLUSION: As a primary colorectal screening tool, CT
      colonography covered by third-party payers has an acceptably low endoscopic
      referral rate and a high concordance of positive findings at optical colonoscopy.

PMID- 16982817
TI  - Phylogeography and ethnogenesis of aboriginal Southeast Asians.
AB  - Studying the genetic history of the Orang Asli of Peninsular Malaysia can provide
      crucial clues to the peopling of Southeast Asia as a whole. We have analyzed
      mitochondrial DNA (mtDNAs) control-region and coding-region markers in 447 mtDNAs
      from the region, including 260 Orang Asli, representative of each of the
      traditional groupings, the Semang, the Senoi, and the Aboriginal Malays, allowing
      us to test hypotheses about their origins. All of the Orang Asli groups have
      undergone high levels of genetic drift, but phylogeographic traces nevertheless
      remain of the ancestry of their maternal lineages. The Semang have a deep
      ancestry within the Malay Peninsula, dating to the initial settlement from Africa
      >50,000 years ago. The Senoi appear to be a composite group, with approximately
      half of the maternal lineages tracing back to the ancestors of the Semang and
      about half to Indochina. This is in agreement with the suggestion that they
      represent the descendants of early Austroasiatic speaking agriculturalists, who
      brought both their language and their technology to the southern part of the
      peninsula approximately 4,000 years ago and coalesced with the indigenous
      population. The Aboriginal Malays are more diverse, and although they show some
      connections with island Southeast Asia, as expected, they also harbor haplogroups
      that are either novel or rare elsewhere. Contrary to expectations, complete mtDNA
      genome sequences from one of these, R9b, suggest an ancestry in Indochina around
      the time of the Last Glacial Maximum, followed by an early-Holocene dispersal
      through the Malay Peninsula into island Southeast Asia.

PMID- 16982818
TI  - On the varied pattern of evolution of 2 fungal genomes: a critique of Hughes and
      Friedman.
AB  - A number of statistical tests have been proposed to detect positive Darwinian
      selection affecting a few amino acid sites in a protein, exemplified by an excess
      of nonsynonymous nucleotide substitutions. These tests are often more powerful
      than pairwise sequence comparison, which averages synonymous (d(S)) and
      nonsynonymous (d(N)) rates over the whole gene. In a recent study, however,
      Hughes AL and Friedman R (2005. Variation in the pattern of synonymous and
      nonsynonymous difference between two fungal genomes. Mol Bio Evol. 22: 1320-1324)
      argue that d(S) and d(N) are expected to fluctuate along the sequence by chance
      and that an excess of nonsynonymous differences in individual codons is no
      evidence for positive selection. The authors compared codons in protein-coding
      genes from the genomes of 2 yeast species, Saccharomyces cerevisiae and
      Saccharomyces paradoxus. They calculated the proportions of synonymous and
      nonsynonymous differences per site (p(S) and p(N)) in every codon and discovered
      that p(N) is often greater than p(S) and that among some codons p(S) and p(N) are
      negatively correlated. The authors argued that these results invalidate previous
      tests of codons under positive selection. Here I discuss several errors of
      statistics in the analysis of Hughes and Friedman, including confusion of
      statistics with parameters, arbitrary data filtering, and derivation of
      hypotheses from data. I also apply likelihood ratio tests of positive selection
      to the yeast data and illustrate empirically that Hughes and Friedman's
      criticisms on such tests are not valid.

PMID- 16982819
TI  - Higher intensity of purifying selection on >90% of the human genes revealed by
      the intrinsic replacement mutation rates.
AB  - For over 3 decades, the rate of replacement mutations has been assumed to be
      equal to, and estimated from, the rate of "strictly" neutral sequence divergence
      in noncoding regions and in silent-codon positions where mutations do not alter
      the amino acid encoded. This assumption is fundamental to estimating the fraction
      of harmful protein mutations and to identifying adaptive evolution at individual
      codons and proteins. We show that the assumption is not justifiable because a
      much larger fraction of codon positions is involved in hypermutable CpG
      dinucleotides as compared with the introns, leading to a higher expected
      replacement mutation rate per site in a vast majority of the genes. Consideration
      of this difference reveals a higher intensity of purifying natural selection than
      previously inferred in human genes. We also show that a much smaller number of
      genes are expected to be evolving with positive selection than that predicted
      using sequence divergence at intron and silent positions in the human genome.
      These patterns indicate the need for using new approaches for estimating rates of
      amino acid-altering mutations in order to find positively selected genes and
      codons in genomes that contain hypermutable CpG's.

PMID- 16982820
TI  - Evolutionary relationships of apusomonads inferred from taxon-rich analyses of 6
      nuclear encoded genes.
AB  - The phylogenetic relationships of the biflagellate protist group Apusomonadidae
      have been unclear despite the availability of some molecular data. We analyzed
      sequences from 6 nuclear encoded genes-small-subunit rRNA, large-subunit rRNA,
      alpha-tubulin, beta-tubulin, actin, and heat shock protein 90-to infer the
      phylogenetic position of Apusomonas proboscidea Alexeieff 1924. To increase the
      taxon richness of the study, we also obtained new sequences from representatives
      of several other major eukaryotic groups: Chrysochromulina sp. National Institute
      for Environmental Studies 1333 (Haptophyta), Cyanophora paradoxa (Glaucophyta),
      Goniomonas truncata (Cryptophyceae), Leucocryptos marina (Kathablepharidae),
      Mesostigma viride (Streptophyta, Viridiplantae), Peridinium limbatum (Alveolata),
      Pterosperma cristatum (Prasinophytae, Viridiplantae), Synura sphagnicola
      (Stramenopiles), and Thaumatomonas sp. (Rhizaria). In most individual gene
      phylogenies, Apusomonas branched close to either of the 2 related taxa
      Opisthokonta (including animals, fungi, and choanoflagellates) or Amoebozoa.
      Combined analyses of all 4 protein-coding genes or all 6 studied genes strongly
      supported the hypothesis that Apusomonadidae is closely related to Opisthokonta
      (or to all other eukaryotic groups except Opisthokonta, depending on the position
      of the eukaryotic root). Alternative hypotheses were rejected in approximately
      unbiased tests at the 5% level. However, the strong phylogenetic signal
      supporting a specific affiliation between Apusomonadidae and Opisthokonta largely
      originated from the alpha-tubulin data. If alpha-tubulin is not considered,
      topologies in which Apusomonadidae is sister to Opisthokonta or is sister to
      Amoebozoa were more or less equally supported. One current model for deep
      eukaryotic evolution holds that eukaryotes are divided into primary "unikont" and
      "bikont" clades and are descended from a "uniflagellate" common ancestor.
      Together with other information, our data suggest instead that unikonts
      (=Opisthokonta and Amoebozoa) are not strictly monophyletic and are descended
      from biflagellate ancestors.

PMID- 16982821
TI  - Interplay of selective pressure and stochastic events directs evolution of the
      MEL172 satellite DNA library in root-knot nematodes.
AB  - According to the library model, related species can have in common satellite DNA
      (satDNA) families amplified in differing abundances, but reasons for persistence
      of particular sequences in the library during long periods of time are poorly
      understood. In this paper, we characterize 3 related satDNAs coexisting in the
      form of a library in mitotic parthenogenetic root-knot nematodes of the genus
      Meloidogyne. Due to sequence similarity and conserved monomer length of 172 bp,
      this group of satDNAs is named MEL172. Analysis of sequence variability patterns
      among monomers of the 3 MEL172 satellites revealed 2 low-variable (LV) domains
      highly reluctant to sequence changes, 2 moderately variable (MV) domains
      characterized by limited number of mutations, and 1 highly variable (HV) domain.
      The latter domain is prone to rapid spread and homogenization of changes.
      Comparison of the 3 MEL172 consensus sequences shows that the LV domains have 6%
      changed nucleotide positions, the MV domains have 48%, whereas 78% divergence is
      concentrated in the HV domain. Conserved distribution of intersatellite
      variability might indicate a complex pattern of interactions in heterochromatin,
      which limits the range and phasing of allowed changes, implying a possible
      selection imposed on monomer sequences. The lack of fixed species-diagnostic
      mutations in each of the examined MEL172 satellites suggests that they existed in
      unaltered form in a common ancestor of extant species. Consequently, the
      evolution of these satellites seems to be driven by interplay of selective
      constraints and stochastic events. We propose that new satellites were derived
      from an ancestral progenitor sequence by nonrandom accumulation of mutations due
      to selective pressure on particular sequence segments. In the library of
      particular taxa, established satellites might be subject to differential
      amplification at chance due to stochastic mechanisms of concerted evolution.

PMID- 16982822
TI  - Rapid onset of ulcerative typhlocolitis in B6.129P2-IL10tm1Cgn (IL-10-/-) mice
      infected with Helicobacter trogontum is associated with decreased colonization by
      altered Schaedler's flora.
AB  - Infection with Helicobacter trogontum, a urease-positive helicobacter isolated
      from subclinically infected rats, was evaluated in B6.129P2-IL10(tm1Cgn)
      (interleukin-10(-/-) [IL-10(-/-)]) and C57BL/6 (B6) mice. In a first experiment,
      IL-10(-/-) mice naturally infected with Helicobacter rodentium had subclinical
      typhlocolitis but developed severe diarrhea and loss of body condition with
      erosive to ulcerative typhlocolitis within 1 to 3 weeks of experimental infection
      with H. trogontum. A second experiment demonstrated that helicobacter-free IL-10(
      /-) mice dosed with H. trogontum also developed severe clinical signs and
      typhlocolitis within 2 to 4 weeks, whereas B6 mice colonized with H. trogontum
      were resistant to disease. In a third experiment, using helicobacter-free IL-10(
      /-) mice, dosing with H. trogontum resulted in acute morbidity and typhlocolitis
      within 8 days. Acute typhlocolitis was accompanied by signs of sepsis supported
      by degenerative hemograms and recovery of Escherichia coli and Proteus spp. from
      the livers of infected mice. Quantitative PCR data revealed that H. rodentium and
      H. trogontum may compete for colonization of the lower bowel, as H. trogontum
      established higher colonization levels in the absence of H. rodentium (P <
      0.003). H. trogontum-induced typhlocolitis was also associated with a significant
      decrease in the levels of colonization by five of eight anaerobes that comprise
      altered Schaedler's flora (P < 0.002). These results demonstrate for the first
      time that H. rodentium infection in IL-10(-/-) mice causes subclinical
      typhlocolitis and that infection with H. trogontum (with or without H. rodentium)
      induces a rapid-onset, erosive to ulcerative typhlocolitis which impacts the
      normal anaerobic flora of the colon and increases the risk of sepsis.

PMID- 16982823
TI  - Single nucleotide polymorphism in the cytolethal distending toxin B gene confers
      heterogeneity in the cytotoxicity of Actinobacillus actinomycetemcomitans.
AB  - Clinical Actinobacillus actinomycetemcomitans produces cytolethal distending
      toxin (CDT) with titers ranging from 10(2) to 10(8) U/mg. Single nucleotide
      polymorphism analysis of the cdt gene in clinical isolates identified a variation
      of a single amino acid at residue 281 of CdtB, which significantly affected CDT
      toxicity by modulating the chromatin-degrading activity of CdtB.

PMID- 16982824
TI  - Lack of in vitro and in vivo recognition of Francisella tularensis subspecies
      lipopolysaccharide by Toll-like receptors.
AB  - Francisella tularensis is an intracellular gram-negative bacterium that is highly
      infectious and potentially lethal. Several subspecies exist of varying
      pathogenicity. Infection by only a few organisms is sufficient to cause disease
      depending on the model system. Lipopolysaccharide (LPS) of gram-negative bacteria
      is generally recognized by Toll-like receptor 4 (TLR4)/MD-2 and induces a strong
      proinflammatory response. Examination of human clinical F. tularensis isolates
      revealed that human virulent type A and type B strains produced lipid A of
      similar structure to the nonhuman model pathogen of mice, Francisella novicida.
      F. novicida LPS or lipid A is neither stimulatory nor an antagonist for human and
      murine cells through TLR4 or TLR2. It does not appear to interact with TLR4 or MD
      2, as it is not an antagonist to other stimulatory LPS. Consistent with these
      observations, aerosolization of F. novicida LPS or whole bacteria induced no
      inflammatory response in mice. These results suggest that poor innate recognition
      of F. tularensis allows the bacterium to evade early recognition by the host
      innate immune system to promote its pathogenesis for mammals.

PMID- 16982825
TI  - Rat strains differ in susceptibility to Ureaplasma parvum-induced urinary tract
      infection and struvite stone formation.
AB  - Individuals with struvite uroliths are susceptible to recurrent urinary tract
      infections (UTI), sepsis, and renal disease. Unfortunately, little is known about
      the host-specific factors that predispose to this disease. In order to develop a
      rodent model that can address this problem, we inoculated female Fischer 344
      (F344), Lewis (LEW), Sprague-Dawley (SD), and Wistar (WIS) rats with a host
      adapted strain of Ureaplasma parvum. Animals were necropsied at 2 weeks
      postinoculation; 100% of F344, 42% of SD, 10% of LEW, and 10% of WIS rats
      remained infected. Severe bladder lesions and struvite calculi were seen in 64%
      of F344 rats; in other rat strains, bladder lesions were mild or absent. F344
      rats with struvite uroliths had the highest urinary levels of proinflammatory
      cytokines, such as GRO/KC, interleukin-1alpha (IL-1alpha), and IL-1beta. F344
      rats without struvite stones at necropsy had milder bladder lesions and
      significantly lower urinary levels of proinflammatory cytokines but a more
      prominent inflammatory response than did other rat strains. Based on our results,
      struvite stone formation is linked to a robust inflammatory response that does
      not resolve UTI but instead promotes damage to surrounding tissues.

PMID- 16982826
TI  - CXCL10/gamma interferon-inducible protein 10-mediated protection against
      Leishmania amazonensis infection in mice.
AB  - Leishmania amazonensis can cause progressive disease in most inbred strains of
      mice. We have previously shown that L. amazonensis-infected C57BL/6 mice have
      profound impairments in expression of proinflammatory cytokines and chemokines
      and in activation of antigen-specific CD4(+) T cells. These impairments are
      independent of interleukin-4 (IL-4) but partially due to IL-10 production. The
      precise mechanism of pathogenesis associated with L. amazonensis infection
      remains largely unresolved. Since chemokines are essential mediators of leukocyte
      recruitment and effector cell function, we hypothesized that these molecules are
      important for the initiation of early responses locally and for the eventual
      control of the infection. In this study, we examined the roles of CXCL10/gamma
      interferon-inducible protein 10 (IP-10) and CCL2/monocyte chemoattractant protein
      1 (MCP-1) in the activation of the macrophage effector function in vitro and
      their efficacy in ameliorating infection in vivo. Bone marrow-derived macrophages
      of both BALB/c and C57BL/6 mice were treated with increasing concentrations of
      recombinant chemokines prior to infection with either stationary-phase
      promastigotes or tissue-derived amastigotes. We found that treatment with IP-10
      or MCP-1 significantly reduced parasite burdens, in a dose-dependent manner, and
      triggered nitric oxide production. When susceptible C57BL/6 mice were injected
      locally with IP-10 following L. amazonensis infection, there was a significant
      delay in lesion development and a reduction in parasite burdens, accompanied by 7
      and 3.5-fold increases in gamma interferon and IL-12 secretion, respectively, in
      restimulated lymph node cells. This study confirms that IP-10 plays a protective
      role in promoting the reduction of intracellular parasites and thereby opens new
      avenues for therapeutic control of nonhealing cutaneous leishmaniasis in the New
      World.

PMID- 16982827
TI  - Effect of different forms of adenylate cyclase toxin of Bordetella pertussis on
      protection afforded by an acellular pertussis vaccine in a murine model.
AB  - Four recombinant forms of the cell-invasive adenylate cyclase toxin (CyaA) of
      Bordetella pertussis were compared for the ability to enhance protection against
      B. pertussis in mice when coadministered with an acellular pertussis vaccine
      (ACV). The four forms were as follows: fully functional CyaA, a CyaA form lacking
      adenylate cyclase enzymatic activity (CyaA*), and the nonacylated forms of these
      toxins, i.e., proCyaA and proCyaA*, respectively. None of these forms alone
      conferred significant (P > 0.05) protection against B. pertussis in a murine
      intranasal challenge model. Mice immunized with ACV alone showed significant (P <
      0.05) reductions in bacterial numbers in the lungs after intranasal challenge
      compared with those for control mice. When administered with ACV, both CyaA and
      CyaA* further reduced bacterial numbers in the lungs of mice after intranasal
      challenge compared with those for ACV-immunized mice, but the enhanced protection
      was only significant (P < 0.05) with CyaA*. Coadministration of CyaA* with ACV
      caused a significant (P < 0.05) increase in immunoglobulin G2a antibody levels
      against pertactin compared with those in mice immunized with ACV alone. Spleen
      cells from mice immunized with ACV plus CyaA* secreted larger amounts of
      interleukin-5 (IL-5), IL-6, gamma interferon (IFN-gamma), and granulocyte
      macrophage colony-stimulating factor (GM-CSF) than did cells from mice immunized
      with ACV plus CyaA or ACV alone after stimulation in vitro with a mixture of B.
      pertussis antigens. Spleen cells from mice immunized with ACV plus CyaA* also
      secreted larger amounts of IFN-gamma and GM-CSF than did cells from mice
      immunized with CyaA* alone after stimulation in vitro with CyaA*. Macrophages
      from mice immunized with ACV plus CyaA* produced significantly (P < 0.05) higher
      levels of nitric oxide than did macrophages from mice immunized with CyaA* alone,
      ACV alone, or ACV plus CyaA after stimulation in vitro with a mixture of B.
      pertussis antigens or heat-killed B. pertussis cells. These data suggest that the
      enhancement of protection provided by CyaA* was due to an augmentation of both
      Th1 and Th2 immune responses to B. pertussis antigens.

PMID- 16982828
TI  - Contribution of FliC to epithelial cell invasion by enterohemorrhagic Escherichia
      coli O113:H21.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O113:H21 can invade epithelial cells.
      In this study, we found that invasion but not adherence was inhibited by anti
      FliC(H21) specific antibodies. In addition, deletion of fliC(H21) from EHEC
      O113:H21 resulted in an eightfold decrease in invasion that was restored upon
      transcomplementation with fliC(H21) but not with fliC(H6). These results
      suggested that FliC plays an important role in the pathogenesis of infections
      caused by EHEC O113:H21 by allowing bacteria to penetrate the intestinal
      epithelium.

PMID- 16982829
TI  - Mouse and human cell activation by N-dodecanoyl-DL-homoserine lactone, a
      Chromobacterium violaceum autoinducer.
AB  - Chromobacterium violaceum produces autoinducers, including homoserine lactones
      (HSLs), for genetic regulation. Among the seven HSLs derived from C. violaceum we
      evaluated, only C(12)-HSL stimulated the production of inflammatory cytokines in
      mammalian monocytic cell lines through the activation of the NF-kappaB signaling
      pathway besides their quorum-sensing role, like 3-oxo-C(12)-HSL from Pseudomonas
      aeruginosa.

PMID- 16982830
TI  - CXCL16 regulates cell-mediated immunity to Salmonella enterica serovar
      Enteritidis via promotion of gamma interferon production.
AB  - CXCL16 is a recently discovered multifaceted chemokine that has been shown not
      only to recruit activated T lymphocytes but also to play a direct role in the
      binding and phagocytosis of bacteria by professional antigen-presenting cells. In
      this study, we investigated the role of CXCL16 in vivo in the regulation of the
      immune response using a murine model of Salmonella enterica serovar Enteritidis
      infection. The expression of CXCL16 was strongly upregulated in the spleens and
      livers of animals developing an immune response to a primary acute infection but
      not in the Peyer's patches. Animals developing a secondary response after
      reexposure to the bacteria displayed a similar pattern of expression. During the
      primary response, prior treatment with neutralizing antibodies to CXCL16 induced
      a significant increase in bacterial burden in the spleen and liver. The
      production of gamma interferon (IFN-gamma) by the lymphocytes in the spleen was
      decreased by anti-CXCL16 treatment. In comparison, during the secondary response,
      anti-CXCL16 treatment also significantly increased bacterial burden in both the
      spleen and liver but had no effect on IFN-gamma production. No role was found for
      CXCL16 in the production of antibody against SefA, a major surface antigen of S.
      enteritidis. Together, these results demonstrate a role for CXCL16 in the control
      of bacterial colonization of target organs and, more specifically, in the
      regulation of the cell-mediated arm of the primary response to S. enteritidis.

PMID- 16982831
TI  - Neutrophil elastase, an innate immunity effector molecule, represses flagellin
      transcription in Pseudomonas aeruginosa.
AB  - Recognition of pathogen-associated molecular patterns (PAMPs) by pattern
      recognition receptors triggers an innate immune response to colonizing or
      invading bacteria. Conversely, many bacteria have evolved mechanisms to dampen
      this response by downregulating the synthesis of such PAMPs. We have previously
      demonstrated that Pseudomonas aeruginosa growing in mucopurulent human
      respiratory mucus from cystic fibrosis patients represses the expression of its
      flagellin, a potent stimulant of the innate immune response. Here we demonstrate
      that this phenomenon occurs in response to the presence of neutrophil elastase in
      such mucus. Nonpurulent mucus from animals had no such repressive effect.
      Furthermore, lysed neutrophils from human blood reproduced the flagellin
      repressive effect ex mucus and, significantly, had no effect on the viability of
      this organism. Neutrophil elastase, a component of the innate host defense
      system, has been described to be bactericidal for gram-negative bacteria and to
      degrade bacterial virulence factors. Thus, the resistance of P. aeruginosa to the
      bactericidal effect of neutrophil elastase, as well as this organism's ability to
      sense this enzyme's presence and downregulate the synthesis of a PAMP, may be the
      key factors in allowing P. aeruginosa to colonize the lungs. These findings
      demonstrate the dynamic nature of this bacterium's response to host defenses that
      ensures its success as a colonizer and also highlights the dual nature of defense
      molecules that confer advantages and disadvantages to both hosts and pathogens.

PMID- 16982832
TI  - Prebiotic galactooligosaccharides reduce adherence of enteropathogenic
      Escherichia coli to tissue culture cells.
AB  - Prebiotic oligosaccharides are thought to provide beneficial effects in the
      gastrointestinal tract of humans and animals by stimulating growth of selected
      members of the intestinal microflora. Another means by which prebiotic
      oligosaccharides may confer health benefits is via their antiadhesive activity.
      Specifically, these oligosaccharides may directly inhibit infections by enteric
      pathogens due to their ability to act as structural mimics of the pathogen
      binding sites that coat the surface of gastrointestinal epithelial cells. In this
      study, the ability of commercial prebiotics to inhibit attachment of microcolony
      forming enteropathogenic Escherichia coli (EPEC) was investigated. The adherence
      of EPEC strain E2348/69 on HEp-2 and Caco-2 cells, in the presence of
      fructooligosaccharides, inulin, galactooligosaccharides (GOS), lactulose, and
      raffinose was determined by cultural enumeration and microscopy. Purified GOS
      exhibited the greatest adherence inhibition on both HEp-2 and Caco-2 cells,
      reducing the adherence of EPEC by 65 and 70%, respectively. In addition, the
      average number of bacteria per microcolony was significantly reduced from 14 to 4
      when GOS was present. Adherence inhibition by GOS was dose dependent, reaching a
      maximum at 16 mg/ml. When GOS was added to adhered EPEC cells, no displacement
      was observed. The expression of BfpA, a bundle-forming-pilus protein involved in
      localized adherence, was not affected by GOS, indicating that adherence
      inhibition was not due to the absence of this adherence factor. In addition, GOS
      did not affect autoaggregation. These observations suggest that some prebiotic
      oligosaccharides may have antiadhesive activity and directly inhibit the
      adherence of pathogens to the host epithelial cell surface.

PMID- 16982833
TI  - Alleles 308A and 238A in the tumor necrosis factor alpha gene promoter do not
      increase the risk of severe malaria in children with Plasmodium falciparum
      infection in Mali.
AB  - The hypothesis that tumor necrosis factor (TNF) aggravates malaria in children is
      supported by observations that TNF polymorphisms and high TNF levels have been
      associated with cerebral malaria. Nevertheless, severe malaria was not associated
      with polymorphisms located at positions -308A and -238A in the TNF alpha gene
      promoter or with a high TNF level in plasma in children from Bamako, Mali.

PMID- 16982834
TI  - Immunogenicity of a Yersinia pestis vaccine antigen monomerized by circular
      permutation.
AB  - Caf1, a chaperone-usher protein from Yersinia pestis, is a major protective
      antigen in the development of subunit vaccines against plague. However,
      recombinant Caf1 forms polymers of indeterminate size. We report the conversion
      of Caf1 from a polymer to a monomer by circular permutation of the gene.
      Biophysical evaluation confirmed that the engineered Caf1 was a folded monomer.
      We compared the immunogenicity of the engineered monomer with polymeric Caf1 in
      antigen presentation assays to CD4 T-cell hybridomas in vitro, as well as in the
      induction of antibody responses and protection against subcutaneous challenge
      with Y. pestis in vivo. In C57BL/6 mice, for which the major H-2(b)-restricted
      immunodominant CD4 T-cell epitopes were intact in the engineered monomer,
      immunogenicity and protective efficacy were preserved, although antibody titers
      were decreased 10-fold. Disruption of an H-2(d)-restricted immunodominant CD4 T
      cell epitope during circular permutation resulted in a compromised T-cell
      response, a low postvaccination antibody titer, and a lack of protection of
      BALB/c mice. The use of circular permutation in vaccine design has not been
      reported previously.

PMID- 16982835
TI  - Monocyte chemoattractant protein 1 does not contribute to protective immunity
      against pneumococcal pneumonia.
AB  - To determine the role of monocyte chemoattractant protein 1 (MCP-1) during
      pneumococcal pneumonia, MCP-1 knockout and wild-type mice were infected with
      Streptococcus pneumoniae. Pulmonary MCP-1 levels were strongly correlated to
      bacterial loads in wild-type mice. However, MCP-1 knockout and wild-type mice
      were indistinguishable with respect to bacterial growth, inflammatory responses,
      and lethality.

PMID- 16982836
TI  - Mycobacterium avium subsp. paratuberculosis PtpA is an endogenous tyrosine
      phosphatase secreted during infection.
AB  - Adaptive gene expression in prokaryotes is mediated by protein kinases and
      phosphatases. These regulatory proteins mediate phosphorylation of histidine or
      aspartate in two-component systems and serine/threonine or tyrosine in eukaryotic
      and eukaryote-like protein kinase systems. The genome sequence of Mycobacterium
      avium subsp. paratuberculosis, the causative agent of Johne's disease, does not
      possess a defined tyrosine kinase. Nevertheless, it encodes for protein tyrosine
      phosphatases. Here, we report that Map1985, is a functional low-molecular
      tyrosine phosphatase that is secreted intracellularly upon macrophage infection.
      This finding suggests that Map1985 might contribute to the pathogenesis of
      Mycobacterium avium subsp. paratuberculosis by dephosphorylating essential
      macrophage signaling and/or adaptor molecules.

PMID- 16982837
TI  - Oral immunization with Acanthamoeba castellanii mannose-binding protein
      ameliorates amoebic keratitis.
AB  - Acanthamoeba castellanii mannose-binding protein (MBP) mediates adhesion of the
      amoebae to corneal epithelial cells, a key first step in the pathogenesis of
      Acanthamoeba keratitis (AK), a devastating corneal infection. In the present
      study, we demonstrate that oral immunization with recombinant MBP ameliorates AK
      in a hamster animal model and that this protection is associated with the
      presence of elevated levels of anti-MBP immunoglobulin A in the tear fluid of the
      immunized animals.

PMID- 16982838
TI  - Identification and characterization of a novel ABC iron transport system, fit, in
      Escherichia coli.
AB  - A putative ABC transporter, fit, with significant homology to several bacterial
      iron transporters was identified in Escherichia coli. The E. coli fit system
      consists of six genes designated fitA, -B, -C, -D, -E, and -R. Based on DNA
      sequence analysis, fit encodes an outer membrane protein (FitA), a periplasmic
      binding protein (FitE), two permease proteins (FitC and -D), an ATPase (FitB),
      and a hypothetical protein (FitR). Introduction of the E. coli fit system into E.
      coli strain K-12 increased intracellular iron content and transformed bacteria
      were more sensitive to streptonigrin, which suggested that fit transports iron in
      E. coli. Expression of fit was studied using a lacZ reporter assay. A functional,
      bidirectional promoter was identified in the intergenic region between genes fitA
      and fitB. The expression of the E. coli fit system was found to be induced by
      iron limitation and repressed when Fe(2+) was added to minimal medium. Several
      fit mutants were created in E. coli using an in vitro transposon mutagenesis
      strategy. Mutations in fit did not affect bacterial growth in iron-restricted
      media. Using a growth promotion test, it was found that fit was not able to
      transport enterobactin, ferrichrome, transferrin, and lactoferrin in E. coli.

PMID- 16982839
TI  - Toll-like receptors differentially regulate CC and CXC chemokines in skeletal
      muscle via NF-kappaB and calcineurin.
AB  - Immunologically active molecules such as cytokines and chemokines have been
      implicated in skeletal muscle weakness during sepsis as well as recovery from
      muscle injury. In sepsis, Toll-like receptors (TLRs) act as key sentinel
      molecules of the innate immune system. Here we determined skeletal muscle cell
      responses of two prototypical CC and CXC chemokine genes (monocyte
      chemoattractant protein 1 [MCP-1] and KC, respectively), to stimulation with
      specific TLR ligands. In addition, we examined whether NF-kappaB and calcineurin
      signaling are involved in these responses. Differentiated myotubes and intact
      whole muscles expressed TLR2, TLR4, TLR5, and TLR9. Stimulation with ligands for
      TLR2 (peptidoglycan) or TLR4 (LPS) elicited robust and equivalent levels of MCP-1
      and KC mRNA expression, whereas stimulation of TLR5 (by flagellin) required gamma
      interferon priming to induce similar effects. Although both TLR2 and TLR4 ligands
      activated the NF-kappaB pathway, NF-kappaB reporter activity was approximately 20
      fold greater after TLR4 stimulation than after TLR2 stimulation. Inhibitory
      effects of NF-kappaB blockade on TLR-mediated chemokine gene expression, by
      either pharmacological (pyrrolidine dithiocarbamate) or molecular (IKKbeta
      dominant-negative transfection) methods, were also more pronounced during TLR4
      stimulation. In contrast, inhibitory effects on TLR-mediated chemokine expression
      of calcineurin blockade (by FK506) were greater for TLR2 than for TLR4
      stimulation. MCP-1 and KC mRNA levels also demonstrated differential responses to
      NF-kappaB and calcineurin blockade during stimulation with specific TLR ligands.
      We conclude that skeletal muscle cells differentially utilize the NF-kappaB and
      calcineurin pathways in a TLR-specific manner to enable complex regulation of CC
      and CXC chemokine gene expression.

PMID- 16982840
TI  - Both influenza-induced neutrophil dysfunction and neutrophil-independent
      mechanisms contribute to increased susceptibility to a secondary Streptococcus
      pneumoniae infection.
AB  - Since secondary Streptococcus pneumoniae infections greatly increase the
      mortality of influenza infections, we determined the relative roles of neutrophil
      dependent and -independent mechanisms in increased susceptibility to S.
      pneumoniae during influenza infection. Mice infected with influenza for 6 days,
      but not 3 days, showed a significant increase in susceptibility to S. pneumoniae
      infection compared to mice not infected with influenza. There was significant
      neutrophil accumulation in the lungs of S. pneumoniae-infected mice regardless of
      whether or not they were infected with influenza for 3 or 6 days. Depletion of
      neutrophils in these mice resulted in increased susceptibility to S. pneumoniae
      in both the non-influenza-infected mice and mice infected with influenza for 3
      days but not in the mice infected with influenza for 6 days, indicating that a
      prior influenza infection of 6 days may compromise neutrophil function, resulting
      in increased susceptibility to a S. pneumoniae infection. Neutrophils from the
      lungs of mice infected with influenza for 3 or 6 days exhibited functional
      impairment in the form of decreased phagocytosis and intracellular reactive
      oxygen species generation in response to S. pneumoniae. In addition, neutrophil
      depleted mice infected with influenza for 6 days were more susceptible to S.
      pneumoniae than neutrophil-depleted mice not infected with influenza, indicating
      that neutrophil-independent mechanisms also contribute to influenza-induced
      increased susceptibility to S. pneumoniae. Pulmonary interleukin-10 levels were
      increased in coinfected mice infected with influenza for 6 days but not 3 days.
      Thus, an influenza infection of 6 days increases susceptibility to S. pneumoniae
      by both suppression of neutrophil function and by neutrophil-independent
      mechanisms such as enhanced cytokine production.

PMID- 16982841
TI  - Differences in the growth of paired Ugandan isolates of Mycobacterium
      tuberculosis within human mononuclear phagocytes correlate with epidemiological
      evidence of strain virulence.
AB  - Previous studies have suggested that isolates of Mycobacterium tuberculosis
      responsible for tuberculosis outbreaks grow more rapidly within human mononuclear
      phagocytes than do other isolates. Clinical scenarios suggesting virulence of
      specific M. tuberculosis isolates are readily identified. Determination of
      appropriate "control" isolates for these studies is more problematic, but equally
      important for validating these assays and, ultimately, for identifying biologic
      differences between M. tuberculosis strains that contribute to virulence. We
      utilized the database from a study of Ugandan tuberculosis patients and their
      household (HH) contacts to identify M. tuberculosis isolates transmitted within
      HH and nontransmitted control isolates. Isolate pairs were evaluated from matched
      HH in each of three clinical scenarios: (i) coprevalent disease and no disease,
      (ii) incident disease and no disease, and (iii) M. tuberculosis infection
      (purified protein derivative [PPD] positive) and no infection (PPD negative).
      Intracellular growth of paired organisms was determined in a blinded fashion
      using two models of intracellular infection in which we have previously
      demonstrated correlation between intracellular growth and strain virulence,
      primary human monocytes (MN) and THP-1 human macrophage-like cells. In both
      models, transmitted isolates from coprevalent disease HH displayed more rapid
      growth than nontransmitted control isolates. In the THP-1 model, this was also
      true of transmitted isolates from HH with incident disease and their controls.
      Differences in production of tumor necrosis factor alpha and interleukin-10 by
      matched isolates showed correlation with growth patterns in the THP-1 cells but
      not in MN. Paired isolates characterized in this manner may be of particular
      interest for further investigations of the virulence of M. tuberculosis.

PMID- 16982842
TI  - Listeria monocytogenes flagella are used for motility, not as adhesins, to
      increase host cell invasion.
AB  - Flagellar structures contribute to the virulence of multiple gastrointestinal
      pathogens either as the effectors of motility, as adhesins, or as a secretion
      apparatus for virulence factors. Listeria monocytogenes is a food-borne, gram
      positive pathogen that uses flagella to increase the efficiency of epithelial
      cell invasion (A. Bigot, H. Pagniez, E. Botton, C. Frehel, I. Dubail, C. Jacquet,
      A. Charbit, and C. Raynaud, Infect. Immun. 73:5530-5539, 2005; L. Dons, E.
      Eriksson, Y. Jin, M. E. Rottenberg, K. Kristensson, C. N. Larsen, J. Bresciani,
      and J. E. Olsen, Infect. Immun. 72:3237-3244, 2004). In this study, we aimed to
      elucidate the mechanism by which flagella contribute to L. monocytogenes
      invasion. To examine the role of flagella as adhesins, invasion and adhesion
      assays were performed with flagellated motile and nonmotile bacteria and
      nonflagellated bacteria. We observed that flagellated but nonmotile bacteria do
      not adhere to or invade human epithelial cells more efficiently than
      nonflagellated bacteria. These results indicated that flagella do not function as
      adhesins to enhance the adhesion of L. monocytogenes to targeted host cells.
      Instead, it appears that motility is important for tissue culture invasion.
      Furthermore, we tested whether motility contributes to early colonization of the
      gastrointestinal tract using a competitive index assay in which mice were
      infected orally with motile and nonmotile bacteria in a 1:1 ratio. Differential
      bacterial counts demonstrated that motile bacteria outcompete nonmotile bacteria
      in the colonization of the intestines at early time points postinfection. This
      difference is also reflected in invasion of the liver 12 h later, suggesting that
      flagellum-mediated motility enhances L. monocytogenes infectivity soon after
      bacterial ingestion in vivo.

PMID- 16982843
TI  - A recombinant attenuated Salmonella enterica serovar Typhimurium vaccine encoding
      Eimeria acervulina antigen offers protection against E. acervulina challenge.
AB  - Coccidiosis is a ubiquitous disease caused by intestinal protozoan parasites
      belonging to several distinct species of the genus Eimeria. Cell-mediated
      immunity (CMI) is critically important for protection against Eimeria; thus, our
      approach utilizes the bacterial type III secretion system (TTSS) to deliver an
      antigen directly into the cell cytoplasm of the immunized host and into the major
      histocompatibility complex class I antigen-processing pathway for induction of
      CMI and antigen-specific cytotoxic T-lymphocyte responses in particular. To
      accomplish this goal, Eimeria genes encoding the sporozoite antigen EASZ240 and
      the merozoite antigen EAMZ250 were fused to the Salmonella enterica serovar
      Typhimurium effector protein gene sptP in the parental pYA3653 vector, yielding
      pYA3657 and pYA3658, respectively. SptP protein is secreted by the TTSS of
      Salmonella and translocated into the cytoplasm of immunized host cells. The host
      strain chromosomal copy of the sptP gene was deleted and replaced by a reporter
      gene, xylE. The newly constructed vectors pYA3657 and pYA3658 were introduced
      into host strain chi8879 (DeltaphoP233 DeltasptP1033::xylEDelta asdA16). This
      strain is an attenuated derivative of the highly virulent strain UK-1. When
      strain chi8879(pYA3653) as the vector control and strain chi8879 harboring
      pYA3657 or pYA3658 were used to orally immunize day-of-hatch chicks, colonization
      of the bursa, spleen, and liver was observed, with peak titers 6 to 9 days
      postimmunization. In vitro experiments show that the EASZ240 antigen is secreted
      into the culture supernatant via the TTSS and that it is delivered into the
      cytoplasm of Int-407 cells by the TTSS. In vivo experiments indicate that both
      humoral and cell-mediated immune responses are induced in chickens vaccinated
      with a recombinant attenuated Salmonella serovar Typhimurium vaccine, which leads
      to significant protection against Eimeria challenge.

PMID- 16982844
TI  - Caveolin-1-deficient mice show defects in innate immunity and inflammatory immune
      response during Salmonella enterica serovar Typhimurium infection.
AB  - A number of studies have shown an association of pathogens with caveolae. To this
      date, however, there are no studies showing a role for caveolin-1 in modulating
      immune responses against pathogens. Interestingly, expression of caveolin-1 has
      been shown to occur in a regulated manner in immune cells in response to
      lipopolysaccharide (LPS). Here, we sought to determine the role of caveolin-1
      (Cav-1) expression in Salmonella pathogenesis. Cav-1(-/-) mice displayed a
      significant decrease in survival when challenged with Salmonella enterica serovar
      Typhimurium. Spleen and tissue burdens were significantly higher in Cav-1(-/-)
      mice. However, infection of Cav-1(-/-) macrophages with serovar Typhimurium did
      not result in differences in bacterial invasion. In addition, Cav-1(-/-) mice
      displayed increased production of inflammatory cytokines, chemokines, and nitric
      oxide. Regardless of this, Cav-1(-/-) mice were unable to control the systemic
      infection of Salmonella. The increased chemokine production in Cav-1(-/-) mice
      resulted in greater infiltration of neutrophils into granulomas but did not alter
      the number of granulomas present. This was accompanied by increased necrosis in
      the liver. However, Cav-1(-/-) macrophages displayed increased inflammatory
      responses and increased nitric oxide production in vitro in response to
      Salmonella LPS. These results show that caveolin-1 plays a key role in regulating
      anti-inflammatory responses in macrophages. Taken together, these data suggest
      that the increased production of toxic mediators from macrophages lacking
      caveolin-1 is likely to be responsible for the marked susceptibility of caveolin
      1-deficient mice to S. enterica serovar Typhimurium.

PMID- 16982845
TI  - Role for matrix metalloproteinase 9 in granuloma formation during pulmonary
      Mycobacterium tuberculosis infection.
AB  - Recent studies have shown that matrix metalloproteinases (MMPs) are induced by
      Mycobacterium tuberculosis during pulmonary infection. Here, expression of MMP-9
      during pulmonary M. tuberculosis infection was characterized to determine whether
      its production correlated with disease resistance in vivo and to determine what
      role, if any, MMP-9 might have in granuloma formation. Following aerosol
      infection with M. tuberculosis, dissemination of bacilli occurred earlier in the
      C57BL/6 resistant mouse strain than in the susceptible CBA/J strain, as was
      evident from an increased number of bacteria in the blood, spleen, and liver at
      day 14 after infection. In addition, early dissemination of the bacilli was
      associated with early induction of protective immunity as assessed from gamma
      interferon levels. Nonspecific blocking of MMPs in C57BL/6 mice early during
      infection reduced hematogenous spread of the bacilli, suggesting that MMPs indeed
      play a role in facilitating dissemination, likely via extracellular matrix
      degradation. The concentration of active MMP-9, specifically, was greater in the
      lungs of C57BL/6 mice than in those of the CBA/J mice at day 28, thereby
      suggesting that MMP-9 is not one of the MMPs directly involved in promoting early
      dissemination of M. tuberculosis. Instead, however, histological lung sections
      and flow cytometric analysis of lung cells from MMP-9-knockout mice showed that
      MMP-9 is involved in macrophage recruitment and granuloma development. These
      combined data support the idea that early MMP activity is an essential component
      of resistance to pulmonary mycobacterial infection and that MMP-9, specifically,
      is required for recruitment of macrophages and tissue remodeling to allow for the
      formation of tight, well-organized granulomas.

PMID- 16982846
TI  - Standardization of immunohistochemistry for formalin-fixed, paraffin-embedded
      tissue sections based on the antigen-retrieval technique: from experiments to
      hypothesis.
AB  - From a practical point of view, one of the most difficult issues in the
      standardization of IHC for FFPE tissue is the adverse influence of formalin upon
      antigenicity, as well as the great variation in fixation/processing procedures.
      Based on previous study, an additional study using four markers demonstrated the
      potential for obtaining equivalent IHC staining among FFPE tissue sections with
      periods of formalin fixation ranging from 6 hr to 30 days. On this basis, the
      following hypothesis is proposed. "The use of optimized AR protocols permits
      retrieval of specific proteins (antigens) from FFPE tissues to a defined and
      reproducible degree (expressed as R%), with reference to the amount of protein
      present in the original fresh/unfixed tissue". This hypothesis may also be
      presented mathematically: the protein amount in a fresh cell/tissue, expressed as
      Pf, produces an IHC signal in fresh tissue of integral(Pf). When the identical
      IHC staining plus AR treatment is applied to a FFPE tissue section, the IHC
      signal may be represented as integral (Pffpe). The degree of retrieval after AR
      (R%) is calculated as follows: R% = integral (Pffpe)/ integral (Pf) x 100%. The
      amount of protein in the FFPE tissue may then be derived as follows: Pffpe = Pf x
      R%. In a situation where optimized AR is 100% effective, the IHC signal would
      then be of equal strength in fresh tissue and FFPE tissue, and Pffpe= Pf. Further
      studies are designed to test the limitations of the proposed hypothesis.

PMID- 16982847
TI  - Developmental biology of the Psammomys obesus pancreas: cloning and expression of
      the Neurogenin-3 gene.
AB  - The desert gerbil Psammomys obesus, an established model of type 2 diabetes
      (T2D), has previously been shown to lack pancreatic and duodenal homeobox gene 1
      (Pdx-1) expression. Pdx-1 deficiency leads to pancreas agenesis in both mice and
      humans. We have therefore further examined the pancreas of P. obesus during
      embryonic development. Using Pdx-1 antisera raised against evolutionary conserved
      epitopes, we failed to detect Pdx-1 immunoreactivity at any time points. However,
      at E14.5, Nkx6.1 immunoreactivity marks the nuclei of all epithelial cells of the
      ventral and dorsal pancreatic buds and the only endocrine cell types found at
      this time point are glucagon and PYY. At E18.5 the pancreas is well branched and
      both glucagon- and ghrelin-positive cells are scattered or found in clusters,
      whereas insulin-positive cells are not found. At E22.5, the acini of the exocrine
      pancreas are starting to mature, and amylase and carboxypeptidase A
      immunoreactivity is found scattered and not in all acini. Ghrelin-, glucagon-,
      PYY-, gastrin-, somatostatin (SS)-, pancreatic polypeptide (PP)-, and insulin
      immunoreactive cells are found scattered or in small groups within or lining the
      developing ductal epithelium as marked by cytokeratin 19. Using degenerate PCR,
      the P. obesus Neurogenin-3 (Ngn-3) gene was cloned. Nucleotide and amino acid
      sequences show high homology with known Ngn-3 sequences. Using specific
      antiserum, we can observe that Ngn-3-immunoreactive cells are rare at E14.5 but
      readily detectable at E18.5 and E22.5. In conclusion, despite the lack of
      detection of Pdx-1, the P. obesus pancreas develops similarly to Muridae species,
      and the Ngn-3 sequence and expression pattern is highly conserved in P. obesus.

PMID- 16982848
TI  - APOBEC3G expression is restricted to epithelial cells of the proximal convoluted
      tubules and is not expressed in the glomeruli of macaques.
AB  - The Vif protein of human immunodeficiency virus-1 (HIV-1) interacts with members
      of the APOBEC family of cytidine deaminases. In this study, we isolated RNA from
      renal cortex as well as from isolated glomeruli and tubulointerstitial fractions
      from two pigtailed macaques that were exsanguinated and perfused with saline. RT
      PCR results indicate that APOBEC3G was detected in the tubule fractions but not
      in the glomerular fractions. Immunoblot analysis using lysates prepared from
      these same fractions and a monoclonal antibody to APOBEC3G confirmed the RT-PCR
      findings. To determine which cell types express APOBEC3G, immunohistochemical
      studies were performed using this monoclonal antibody on renal cortical sections.
      Our results clearly show that the glomeruli do not express APOBEC3G but that
      select tubules within the cortex express APOBEC3G at high levels. To further
      differentiate the distribution of APOBEC3G expression, serial sections were
      stained with the lectins Dolichos biflorus agglutinin (DBA) and Phaseolus
      vulgaris erythroagglutinin (PHA-E), which differentially bind to epithelial cells
      of the tubules and glomeruli. Our results indicate that APOBEC3G expression was
      restricted to PHA-E-staining tubules and not DBA-staining tubules, suggesting
      that APOBEC3G expression was restricted to proximal convoluted tubules. These
      findings suggest that infection of epithelial cells of proximal renal tubules
      could suppress Vif-defective HIV-1 replication, whereas infection of cells of the
      glomeruli, a major target of HIV-associated nephropathy, could act as a reservoir
      for the replication of Vif-defective HIV-1.

PMID- 16982849
TI  - Expression studies of neogenin and its ligand hemojuvelin in mouse tissues.
AB  - Juvenile hemochromatosis is a severe hereditary iron overload disease caused by
      mutations in the HJV (hemojuvelin) and HAMP (hepcidin) genes. Hepcidin is an
      important iron regulatory hormone, and hemojuvelin may regulate hepcidin
      synthesis via the multifunctional membrane receptor neogenin. We explored the
      expression of murine hemojuvelin and neogenin mRNAs and protein. Real-time RT-PCR
      analysis of 18 tissues from male and female mice was performed to examine the
      mRNA expression profiles. To further study protein expression and localization we
      used immunohistochemistry on several tissues from three mouse strains. Mouse Neo1
      mRNA was detectable in the 18 tissues tested, the highest signals being evident
      in the ovary, uterus, and testis. Neogenin protein was observed in the brain,
      skeletal muscle, heart, liver, stomach, duodenum, ileum, colon, renal cortex,
      lung, testis, ovary, oviduct, and uterus. The spleen, thymus, and pancreas were
      negative for neogenin. The highest signals for Hjv mRNA were detectable in the
      skeletal muscle, heart, esophagus, and liver. The results indicate that Neo1 mRNA
      is widely expressed in both male and female mouse tissues with the highest
      signals detected in the reproductive system. Moreover, Hjv and Neo1 mRNAs are
      simultaneously expressed in skeletal muscle, heart, esophagus, and liver.

PMID- 16982850
TI  - Distribution of pancreatic endocrine cells including IAPP-expressing cells in non
      diabetic and type 2 diabetic cases.
AB  - There is a lack of agreement on the distribution of islet amyloid polypeptide
      (IAPP) in the pancreases of healthy and diabetic subjects. Therefore, a detailed
      morphometrical and immunohistochemical study was performed to obtain information
      on the distribution of cells expressing insulin, glucagon, somatostatin,
      pancreatic polypeptide (PP), and IAPP in the pancreases of non-diabetic (n=4) and
      diabetic individuals (n=6). In the non-diabetic cases, beta-cells contributed to
      approximately 64%, alpha-cells to 26%, delta-cells to 8%, PP cells to 0.3%, and
      IAPP cells to 34% of the islet cell population. The ratio of IAPP/insulin was
      approximately 1:2. In diabetic cases, beta-cells were decreased by 24%, and IAPP
      was decreased by 57%. The alpha- and delta-cells were increased by 40% and 58%,
      respectively. IAPP/insulin ratio was decreased by 41%. Thus, only 50% of the beta
      cells in non-diabetics and only 30% in diabetics coexpressed IAPP. In diabetics,
      more delta-cells coexpressed IAPP than in non-diabetics. The results seem to
      argue against the notion that the secretion of IAPP is increased in diabetics. It
      is possible that an increase in somatostatin and glucagon plays a greater role in
      diabetes than IAPP.

PMID- 16982851
TI  - Expression of ABCA3 in developing lung and other tissues.
AB  - ABCA3 is a member of the ATP-binding cassette (ABC) family of transport proteins
      and is required for perinatal respiratory adaptation. Monoclonal and polyclonal
      antibodies were generated against a recombinant human ABCA3 peptide and used to
      assess its expression in the developing lung and adult tissues. Immunostaining
      for ABCA3 was detected at highest levels in type II epithelial cells of the lung
      but was also noted in other organs including liver, stomach, kidney, adrenal,
      pancreas, trachea, and brain. In the fetal lung, ABCA3 staining and mRNA
      increased prior to birth. Like other surfactant protein genes, ABCA3 expression
      was induced by thyroid transcription factor-1 in vitro. ABCA3 was coexpressed
      with SP-B and proSP-C in type II epithelial cells. ABCA3 staining was detected
      surrounding large, intracellular organelles consistent with its association with
      lamellar bodies. In the human fetal lung, ABCA3 staining was not detected prior
      to 22-23 weeks of gestation, except in the presence of pulmonary inflammation.
      ABCA3 was detected in type II epithelial cells of the human lung from 28 weeks of
      gestation and thereafter. Postnatally, intense ABCA3 staining was observed in
      hyperplastic epithelial cells relining injured airways in infants with chronic
      lung disease. Localization and regulation of ABCA3 in the respiratory epithelium
      is consistent with its proposed role in surfactant homeostasis. The role of ABCA3
      in extrapulmonary tissues and organs remains to be elucidated. This manuscript
      contains online supplemental material at (www.jhc.org). Please visit this article
      online to view these materials.

PMID- 16982852
TI  - Antibody wars: extreme diversity.

PMID- 16982853
TI  - Pillars Article: Origin of antibody variation. Nature 1966. 211: 242-243.

PMID- 16982854
TI  - The inflammatory caspases: key players in the host response to pathogenic
      invasion and sepsis.
AB  - Caspases are cysteinyl-aspartate-specific proteinases known for their role in
      apoptosis (cell death or apoptotic caspases) and proinflammatory cytokine
      maturation (inflammatory caspases). The inflammatory caspases were among the
      first to be discovered, but only recently have the mechanisms leading to their
      activation and inhibition begun to be elucidated. In this review, we examine the
      biochemistry, substrates, and function of this unique family of inflammatory
      proteases, highlight the most recent findings regarding their regulatory
      mechanisms, and discuss what remains to be understood about their roles in health
      and disease.

PMID- 16982855
TI  - Cutting edge: IL-7-independent regulation of IL-7 receptor alpha expression and
      memory CD8 T cell development.
AB  - Expression of IL-7Ralpha on a subset of Ag-specific effector CD8 T cells is
      believed to identify memory cell precursors. However, whether IL-7 regulates IL
      7Ralpha expression in vivo and is responsible for selective survival of IL
      7Ralpha(+) effector cells is unknown. Our results show that in the absence of IL
      7, IL-7Ralpha expression was extinguished on the majority of CD8 T cells
      responding to virus infection, sustained on a subset of effector cells
      transitioning to memory, and expressed at high levels by memory cells.
      Additionally, an IL-7-deficient environment was capable of supporting bcl-2 up
      regulation and memory cell development in response to virus infection. Thus, IL
      7Ralpha regulation occurs independently of IL-7 in responding CD8 T cells,
      indicating that CD8 memory T cell precursors are not selected by IL-7/IL-7Ralpha
      interactions.

PMID- 16982856
TI  - Cutting edge: ASC mediates the induction of multiple cytokines by Porphyromonas
      gingivalis via caspase-1-dependent and -independent pathways.
AB  - Porphyromonas gingivalis (Pg) is a major etiologic agent for chronic
      periodontitis. Tissue destruction by Pg results partly from induction of host
      inflammatory responses through TLR2 signaling. This work examines the role of
      apoptosis-associated speck-like protein containing a caspase-recruitment domain
      (ASC), an adaptor molecule important for TLR-mediated caspase-1 activation.
      Results demonstrate that ASC levels are stable upon infection of human THP1
      monocytic cells with Pg but decrease after cytokine induction. Using short
      hairpin RNA, we demonstrate an essential role for ASC in induction of IL-1beta by
      TLR2, 4, and 5 agonists, live Escherichia coli, and Pg. Induction of IL-6, IL-8,
      IL-10, and TNF also requires ASC, but this induction is not inhibited by IL-1
      receptor antagonist or caspase-1 inhibitor. Similar results in U937 indicate
      broad applicability of these findings. Pg-infected ASC knockdown THP1 cells
      exhibit reduced transcript levels and NF-kappaB activation. These results suggest
      a role for ASC in cytokine induction by Pg involving both caspase-1-dependent and
      -independent mechanisms.

PMID- 16982857
TI  - Cutting edge: Paracrine, but not autocrine, IL-2 signaling is sustained during
      early antiviral CD4 T cell response.
AB  - IL-2 is expressed predominantly by activated T cells, and regulates T cell
      function by activating, via its receptor, the latent transcription factor STAT5.
      This signaling can occur in either a paracrine (between cells) or an autocrine
      (same cell) manner, although the kinetics by which these two signaling modes
      operate during in vivo T cell responses are unknown. In the current study, IL-2
      expression and signaling in a clonotypic population of antiviral CD4+ T cells was
      analyzed by flow cytometry during the initial 24 h of priming. IL-2 expression
      and STAT5 activation peaked in parallel, but surprisingly, were almost completely
      mutually exclusive. Thus, only paracrine IL-2 signaling could be observed. As an
      additional indication of the efficiency of paracrine IL-2 signaling, polyclonal
      CD4+CD25+Foxp3+ regulatory T cells displayed detectable STAT5 activation under
      steady-state conditions, which was strongly enhanced by neighboring IL-2
      expressing antiviral CD4 cells.

PMID- 16982858
TI  - Cutting edge: T cell requirement for CD28 costimulation is due to negative
      regulation of TCR signals by PTEN.
AB  - Recent studies suggest that the phosphatase and tensin homolog deleted on
      chromosome 10 (PTEN) plays a critical role in the maintenance of self-tolerance.
      Using T cell-specific PTEN knockout mice (PTENDeltaT), we have identified a novel
      mechanism by which PTEN regulates T cell tolerance. We found that TCR stimulation
      alone, without CD28 costimulation, is sufficient to induce hyperactivation of the
      PI3K pathway, which leads to enhanced IL-2 production by naive PTENDeltaT T
      cells. Importantly, as a result of this increased response to TCR stimulation,
      PTENDeltaT CD4(+) T cells no longer require CD28 costimulation for in vitro or in
      vivo expansion. In fact, unlike wild-type T cells, PTENDeltaT CD4(+) T cells are
      not anergized by delivery of TCR stimulation alone. These data suggest that by
      negatively regulating TCR signals, PTEN imposes a requirement for CD28
      costimulation, thus defining a novel mechanism for its role in self-tolerance.

PMID- 16982859
TI  - Cutting edge: IL-1beta mediates the proangiogenic activity of osteopontin
      activated human monocytes.
AB  - Inflammation plays an important role in the onset of angiogenesis. In the present
      study, we show that osteopontin (OPN), a proinflammatory mediator involved in
      tissue repair, induces IL-1beta up-regulation in human monocytes. This was
      accompanied by the enhanced production of TNF-alpha, IL-8, and IL-6, a decreased
      release of IL-10, and increased p38 phosphorylation. The supernatants of OPN
      treated monocytes were highly angiogenic when delivered on the chick embryo
      chorioallantoic membrane. The angiogenic response was completely abrogated by a
      neutralizing anti-IL-1 Ab, thus indicating that this cytokine represents the
      major proangiogenic factor expressed by OPN-activated monocytes. Accordingly, rIL
      1beta mimicked the proangiogenic activity of OPN-treated monocyte supernatants,
      and IL-1R (type I) was found to be expressed in the chorioallantoic membrane. In
      conclusion, OPN-activated monocytes may contribute to the onset of angiogenesis
      through a mechanism mediated by IL-1beta.

PMID- 16982860
TI  - Cutting edge: rho activation and actin polarization are dependent on plexin-A1 in
      dendritic cells.
AB  - We recently identified expression of the semaphorin receptor, plexin-A1, in
      dendritic cells (DCs); however, its function in these cells remains to be
      elucidated. To investigate function and maximize physiological relevance, we
      devised a retroviral approach to ablate plexin-A1 gene expression using small
      hairpin RNA (shRNA) in primary bone marrow-derived DCs. We show that plexin-A1
      localizes within the cytoplasm of immature DCs, becomes membrane-associated, and
      is enriched at the immune synapse in mature DCs. Reducing plexin-A1 expression
      with shRNA greatly reduced actin polarization as well as Rho activation without
      affecting Rac or Cdc42 activation. A Rho inhibitor, C3, also reduced actin
      polarization. These changes were accompanied by the near-ablation of T cell
      activation. We propose a mechanism of adaptive immune regulation in which plexin
      A1 controls Rho activation and actin cytoskeletal rearrangements in DCs that is
      associated with enhanced DC-T cell interactions.

PMID- 16982861
TI  - Cutting edge: Uniqueness of lymphoid chemokine requirement for the initiation and
      maturation of nasopharynx-associated lymphoid tissue organogenesis.
AB  - CD3(-)CD4(+)CD45(+) inducer cells are required for the initiation of mucosa
      associated organogenesis of both nasopharynx-associated lymphoid tissues (NALT)
      and Peyer's patches (PP) in the aerodigestive tract. CXCL13(-/-) mice and mice
      carrying the paucity of lymph node T cell (plt) mutation and lacking expression
      of CCL19 and CCL21 accumulate CD3(-)CD4(+)CD45(+) cells at the site of NALT but
      not of PP genesis. Although NALT was observed to develop in adult CXCL13(-/-) and
      plt/plt mice, the formation of germinal centers in CXCL13(-/-) mice was affected,
      and their population of B cells was much lower than in the NALT of CXCL13(+/-)
      mice. Similarly, fewer T cells were observed in the NALT of plt/plt mice than in
      control mice. These findings indicate that the initiation of NALT organogenesis
      is independent of CXCL13, CCL19, and CCL21. However, the expression of these
      lymphoid chemokines is essential for the maturation of NALT microarchitecture.

PMID- 16982862
TI  - Preferential involvement of Tim-3 in the regulation of hepatic CD8+ T cells in
      murine acute graft-versus-host disease.
AB  - Tim-3, a member of the T cell Ig mucin (TIM) family regulates effector Th1
      responses. We examined Tim-3 and its ligand expression as well as the effects of
      anti-Tim-3 mAb treatment in a murine model of acute graft-vs-host disease
      (aGVHD). In mice with aGVHD, Tim-3 expression was markedly up-regulated on
      splenic and hepatic CD4+ and CD8+ T cells, dendritic cells (DCs), and
      macrophages, and this was especially dramatic in hepatic CD8+ T cells. Both donor
      and host-derived CD8+ T cells induced similar levels of Tim-3. Tim-3 ligand
      expression was also up-regulated in splenic T cells, DCs, and macrophages, but
      not in the hepatic lymphocytes. The administration of anti-Tim-3 mAbs accelerated
      aGVHD, as demonstrated by body weight loss, reduction in total splenocyte number,
      and infiltration of lymphocytes in the liver. IFN-gamma expression by splenic and
      hepatic CD4+ and CD8+ T cells was significantly augmented by anti-Tim-3 mAb
      treatment. In addition, the cytotoxicity against host alloantigen by donor CD8+ T
      cells was enhanced. These results demonstrate that the anti-Tim-3 treatment in
      aGVHD augmented the activation of effector T cells expressing IFN-gamma or
      exerting cytotoxicity. Our results suggest that Tim-3 may play a crucial role in
      the regulation of CD8+ T cells responsible for the maintenance of hepatic
      homeostasis and tolerance.

PMID- 16982863
TI  - Combination of vaccination and chimeric receptor expressing T cells provides
      improved active therapy of tumors.
AB  - We have generated murine T cells expressing chimeric immune receptors (CR)
      against human 5T4 oncofetal Ag (h5T4) and evaluated their tumor therapeutic
      efficacy alone and in combination with immunization using a replication-defective
      adenovirus encoding h5T4 (Rad.h5T4) and bone marrow-derived dendritic cells
      (BMDC). The h5T4-specific engineered T cells demonstrated Ag-specific, non-MHC
      restricted cytolysis of h5T4-positive B16 and CT26 tumor cells in vitro by
      cytotoxicity assay and antitumor activity in vivo using a Winn assay. In the s.c.
      injected B16h5T4 melanoma model, early local but not systemic i.v. administration
      of syngeneic h5T4-specific CR T cells significantly increased mice survival. This
      improvement was further enhanced when combined with immunization with Rad.h5T4,
      followed by post-CR T cell treatment with BMDC in the active therapy model,
      possibly through mechanisms of enhancing Ag-specific cellular immune responses.
      This synergistic effect was lost without delivery of the BMDC. Our findings
      suggest that combining engineered T cells with specific vaccination strategies
      can improve the active tumor therapy.

PMID- 16982864
TI  - Dual ligand stimulation of RAW 264.7 cells uncovers feedback mechanisms that
      regulate TLR-mediated gene expression.
AB  - To characterize how signaling by TLR ligands can be modulated by non-TLR ligands,
      murine RAW 264.7 cells were treated with LPS, IFN-gamma, 2-methyl-thio-ATP (2MA),
      PGE(2), and isoproterenol (ISO). Ligands were applied individually and in
      combination with LPS, for 1, 2, and 4 h, and transcriptional changes were
      measured using customized oligo arrays. We used nonadditive transcriptional
      responses to dual ligands (responses that were reproducibly greater or less than
      the expected additive responses) as a measure of pathway interaction. Our
      analysis suggests that cross-talk is limited; <24% of the features with
      significant responses to the single ligands responded nonadditively to a dual
      ligand pair. PGE(2) and ISO mainly attenuated, while 2MA enhanced, LPS-induced
      transcriptional changes. IFN-gamma and LPS cross-regulated the transcriptional
      response induced by each other: while LPS preferentially enhanced IFN-gamma
      induced changes in gene expression at 1 h, IFN-gamma signaling primarily
      attenuated LPS-induced changes at 4 h. Our data suggest specific cross-talk
      mechanisms: 1) LPS enhances the expression of IFN-gamma-response genes by
      augmenting STAT1 activity and by activating NF-kappaB, which synergizes with IFN
      gamma-induced transcriptional factors; 2) IFN-gamma attenuates the late LPS
      transcriptional response by increasing the expression of suppressor of cytokine
      signaling 1 and cytokine-inducible SH2-containing protein expression; 3) 2MA
      modulates LPS secondary transcriptional response by increasing IFN-beta and
      inhibiting IL-10 gene expression; 4) PGE(2) and ISO similarly regulate the LPS
      transcriptional response. They increase IL-10 transcription, resulting in
      attenuated expression of known IL-10-suppressed genes.

PMID- 16982865
TI  - T cell, Ig domain, mucin domain-2 gene-deficient mice reveal a novel mechanism
      for the regulation of Th2 immune responses and airway inflammation.
AB  - The development of asthma and other atopic diseases is influenced by cytokines
      produced by Th2 effector T cells. How effector T cell responses are regulated
      once these cell populations are established remains unclear. The recently
      described T cell and airway phenotype regulator locus, containing the T cell, Ig
      domain, mucin domain (TIM) genes, is genetically associated with Th2 cytokine
      production and Th2-dependent immune responses. In this study, we report the
      phenotype of the TIM-2 gene-deficient mouse, and demonstrate exacerbated lung
      inflammation in an airway atopic response model. Immune responses in the TIM-2
      deficient mouse reveal disregulated expression of Th2 cytokines, and adoptive
      transfer experiments show that the T cell compartment is responsible for the
      heightened inflammatory phenotype. These studies show that TIM-2 is a novel and
      critical regulator of effector T cell activity.

PMID- 16982866
TI  - Transient receptor potential vanilloid subtype 1 mediates microglial cell death
      in vivo and in vitro via Ca2+-mediated mitochondrial damage and cytochrome c
      release.
AB  - The present study examined the expression of transient receptor potential
      vanilloid subtype 1 (TRPV1) in microglia, and its association with microglial
      cell death. In vitro cell cultures, RT-PCR, Western blot analysis, and
      immunocytochemical staining experiments revealed that rat microglia and a human
      microglia cell line (HMO6) showed TRPV1 expression. Furthermore, exposure of
      these cells to TRPV1 agonists, capsaicin (CAP) and resiniferatoxin (RTX),
      triggered cell death. This effect was ameliorated by the TRPV1 antagonists,
      capsazepine and iodo-resiniferatoxin (I-RTX), suggesting that TRPV1 is directly
      involved. Further examinations revealed that TRPV1-induced toxicity was
      accompanied by increases in intracellular Ca(2+), and mitochondrial damage; these
      effects were inhibited by capsazepine, I-RTX, and the intracellular Ca(2+)
      chelator BAPTA-AM. Treatment of cells with CAP or RTX led to increased
      mitochondrial cytochrome c release and enhanced immunoreactivity to cleaved
      caspase-3. In contrast, the caspase-3 inhibitor z-DEVD-fmk protected microglia
      from CAP- or RTX-induced toxicity. In vivo, we also found that intranigral
      injection of CAP or 12-hydroperoxyeicosatetraenoic acid, an endogenous agonist of
      TRPV1, into the rat brain produced microglial damage via TRPV1 in the substantia
      nigra, as visualized by immunocytochemistry. To our knowledge, this study is the
      first to demonstrate that microglia express TRPV1, and that activation of this
      receptor may contribute to microglial damage via Ca(2+) signaling and
      mitochondrial disruption.

PMID- 16982867
TI  - Three memory subsets of human CD8+ T cells differently expressing three cytolytic
      effector molecules.
AB  - Multicolor flow cytometric analysis for the expression of three effector
      molecules, i.e., perforin (Per), granzyme A (GraA), and granzyme B (GraB), in
      human CD8(+) T cells demonstrated that they included five subpopulations,
      implying the following pathway for the differentiation of CD8(+) T cells: Per(
      )GraA(-)GraB(-)-->Per(-)GraA(+)GraB(-)-->Per(low)GraA(+)GraB(-)-->
      Per(low)GraA(+)GraB(+)-->Per(high)GraA(+)GraB(+). The analysis of the expression
      of these molecules in the subsets classified by the combination of the expression
      of CCR7 and CD45RA or by that of CD27, CD28, and CD45RA showed that functional
      CD8(+) T cell subsets could be partially identified by these phenotypic
      classifications. However, the functional subsets could be precisely identified by
      the classification using five cell surface markers or three cell surface markers
      and three cytolytic molecules. Per(-)GraA(-)GraB(-) and Per(-/low)GraA(+)GraB(-)
      cells were predominantly found in CCR5(-)CCR7(+) and CCR5(high/low)CCR7(-)
      subsets, respectively, of CD8(+) T cells expressing the CD27(+)CD28(+)CD45RA(-)
      phenotype, whereas Per(low)GraA(+)GraB(+) cells were found in the CCR5(low)CCR7(
      ) subset of those expressing this phenotype and in a part of the CCR5(-/low)CCR7(
      ) subset of those expressing the CD27(-/low)CD28(-)CD45RA(-/+) phenotype. Ex vivo
      EBV-specific CD8(+) T cells, which were Per(low/-)GraA(+)GraB(-/+) cells, hardly
      or very weakly killed the target cells, indicating that these were not effector T
      cells. These findings suggest that the Per(-)GraA(-)GraB(-), Per(
      /low)GraA(+)GraB(-), and Per(low)GraA(+)GraB(+) cells were central memory, early
      effector memory, and late effector memory T cells, respectively. Per(
      /low)GraA(+)GraB(-) cells gained GraB expression after TCR stimulation,
      indicating that early effector memory T cells could differentiate into late
      effector and effector T cells. The present study showed the existence of three
      memory subsets and the pathway for their differentiation.

PMID- 16982868
TI  - The human CD77- B cell population represents a heterogeneous subset of cells
      comprising centroblasts, centrocytes, and plasmablasts, prompting phenotypical
      revision.
AB  - The process of becoming an Ig-producing plasma cell takes the mature B cell
      through the germinal center, where Ig genes are diversified through somatic
      hypermutation and class switch recombination. To more clearly define functional
      characteristics of the germinal center dark zone centroblasts and the light zone
      centrocytes, we have performed expression analysis of the CD77(+) and CD77(-)
      populations, because CD77 has been accepted as a discriminator of centroblasts
      and centrocytes. Our results demonstrated that the CD77(+) and the CD77(-)
      populations lack functional associated expression programs discriminating the two
      populations. Both populations are shown to be actively cycling and to share
      common features associated with cell cycle regulation and DNA maintenance. They
      are also shown to have an equally active DNA repair program, as well as
      components involved in somatic hypermutation and class switch recombination.
      Moreover, the data also demonstrated that the CD77(-) population comprises cells
      with an already initiated plasma cell differentiation program. Together this
      demonstrates that CD77 does not discriminate centroblasts and centrocytes and
      that the CD77(-) population represents a heterogeneous subset of cells,
      comprising centroblasts, centrocytes, and plasmablast.

PMID- 16982869
TI  - Cigarette smoke-induced pulmonary inflammation and emphysema are attenuated in
      CCR6-deficient mice.
AB  - Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette
      smoking, and is characterized by an increase in inflammatory cells in the airways
      and pulmonary tissue. The chemokine receptor CCR6 and its ligand MIP-3alpha/CCL20
      may be involved in the recruitment of these inflammatory cells. To investigate
      the role of CCR6 in the pathogenesis of COPD, we analyzed the inflammatory
      responses of CCR6 knockout (KO) and wild-type mice upon cigarette smoke (CS)
      exposure. Both subacute and chronic exposure to CS induced an increase in cells
      of the innate and adaptive immune system in the bronchoalveolar lavage, both in
      CCR6 KO and wild-type mice. However, the accumulation of dendritic cells,
      neutrophils, and T lymphocytes, which express CCR6, was significantly attenuated
      in the CCR6 KO mice, compared with their wild-type littermates. In the lung
      tissue of CCR6 KO mice, there was an impaired increase in dendritic cells,
      activated CD8(+) T lymphocytes, and granulocytes. Moreover, this attenuated
      inflammatory response in CCR6 KO mice offered a partial protection against
      pulmonary emphysema, which correlated with an impaired production of MMP-12.
      Importantly, protein levels of MIP-3alpha/CCL20, the only chemokine ligand of the
      CCR6 receptor, and MCP-1/CCL2 were significantly increased upon CS exposure in
      wild-type, but not in CCR6 KO mice. In contrast, CCR6 deficiency had no effect on
      the development of airway wall remodeling upon chronic CS exposure. These results
      indicate that the interaction of CCR6 with its ligand MIP-3alpha contributes to
      the pathogenesis of CS-induced pulmonary inflammation and emphysema in this
      murine model of COPD.

PMID- 16982870
TI  - Identification and characterization of the precursors committed to osteoclasts
      induced by TNF-related activation-induced cytokine/receptor activator of NF-kappa
      B ligand.
AB  - Osteoclasts are terminally differentiated from cells of monocyte/macrophage
      lineage by stimulation with TNF-related activation-induced cytokine (TRANCE)
      (receptor activator of NF-kappaB ligand/osteoprotegerin ligand/osteoclast
      differentiation factor/TNFSF11/CD254). In the present study, we attempted to
      determine when and how the cell fate of precursors becomes committed to
      osteoclasts following TRANCE stimulation. Although mouse bone marrow-derived
      macrophages (BMMs) were able to differentiate into either osteoclasts or
      dendritic cells, the cells no longer differentiated into dendritic cells after
      treatment with TRANCE for 24 h, indicating that their cell fate was committed to
      osteoclasts. Committed cells as well as BMMs were still quite weak in tartrate
      resistant acid phosphatase activity, an osteoclast marker, and incorporated
      zymosan particles by phagocytosis. Interestingly, committed cells, but not BMMs,
      could still differentiate into osteoclasts even after incorporation of the
      zymosan particles. Furthermore, IL-4 and IFN-gamma, potent inhibitors of
      osteoclast differentiation, failed to inhibit osteoclast differentiation from
      committed cells, and blocking of TRANCE stimulation by osteoprotegerin resulted
      in cell death. Adhesion to culture plates was believed to be essential for
      osteoclast differentiation; however, committed cells, but not BMMs,
      differentiated into multinucleated osteoclasts without adhesion to culture
      plates. Although LPS activated the NF-kappaB-mediated pathway in BMMs as well as
      in committed cells, the mRNA expression level of TNF-alpha in the committed cells
      was significantly lower than that in BMMs. These results suggest that
      characteristics of the committed cells induced by TRANCE are distinctively
      different from that of BMMs and osteoclasts.

PMID- 16982871
TI  - Inhibitory role of IFN-gamma-inducible lysosomal thiol reductase in T cell
      activation.
AB  - IFN-gamma-inducible lysosomal thiol reductase (GILT) is a unique thiol reductase
      with optimal enzymatic activity at low pH. GILT plays a crucial role in unfolding
      the antigenic proteins in preparation for their proteolytic cleavage and
      presentation of resulting peptides by MHC class II. In this study, we demonstrate
      that GILT is expressed in T lymphocytes and that it has an APC-nonrelated role in
      the regulation of T cell activation. Surprisingly, comparison of wild-type and
      GILT-deficient T cell activation in vitro revealed stronger responsiveness in the
      absence of GILT. The effect of GILT in reducing the proliferative and cytotoxic
      responses was endogenous to T cells and resulted from decreased sensitivity at
      the individual cell level. Therefore, a molecule with primarily lysosomal
      localization suppresses T cell activation, a process characterized by signal
      transmission from plasma membrane to cytoplasm and nucleus.

PMID- 16982872
TI  - Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in
      vivo.
AB  - Naturally occurring CD4+ regulatory T cells (T(R)) that express CD25 and the
      transcription factor FoxP3 play a key role in immune homeostasis, preventing
      immune pathological responses to self and foreign Ags. CTLA-4 is expressed by a
      high percentage of these cells, and is often considered as a marker for T(R) in
      experimental and clinical analysis. However, it has not yet been proven that CTLA
      4 has a direct role in T(R) function. In this study, using a T cell-mediated
      colitis model, we demonstrate that anti-CTLA-4 mAb treatment inhibits T(R)
      function in vivo via direct effects on CTLA-4-expressing T(R), and not via
      hyperactivation of colitogenic effector T cells. Although anti-CTLA-4 mAb
      treatment completely inhibits T(R) function, it does not reduce T(R) numbers or
      their homing to the GALT, suggesting the Ab mediates its function by blockade of
      a signal required for T(R) activity. In contrast to the striking effect of the
      Ab, CTLA-4-deficient mice can produce functional T(R), suggesting that under some
      circumstances other immune regulatory mechanisms, including the production of IL
      10, are able to compensate for the loss of the CTLA-4-mediated pathway. This
      study provides direct evidence that CTLA-4 has a specific, nonredundant role in
      the function of normal T(R). This role has to be taken into account when
      targeting CTLA-4 for therapeutic purposes, as such a strategy will not only boost
      effector T cell responses, but might also break T(R)-mediated self-tolerance.

PMID- 16982873
TI  - Induction of autoimmunity by expansion of autoreactive CD4+CD62Llow cells in
      vivo.
AB  - The prerequisites of peripheral activation of self-specific CD4(+) T cells that
      determine the development of autoimmunity are incompletely understood. SJL mice
      immunized with myelin proteolipid protein (PLP) 139-151 developed experimental
      autoimmune encephalomyelitis (EAE) when pertussis toxin (PT) was injected at the
      time of immunization but not when injected 6 days later, indicating that PT
      induced alterations of the peripheral immune response lead to the development of
      autoimmunity. Further analysis using IA(s)/PLP(139-151) tetramers revealed that
      PT did not change effector T cell activation or regulatory T cell numbers but
      enhanced IFN-gamma production by self-specific CD4(+) T cells. In addition, PT
      promoted the generation of CD4(+)CD62L(low) effector T cells in vivo. Upon
      adoptive transfer, these cells were more potent than CD4(+)CD62L(high) cells in
      inducing autoimmunity in recipient mice. The generation of this population was
      paralleled by higher expression of the costimulatory molecules CD80, CD86, and B7
      DC, but not B7-RP, PD-1, and B7-H1 on CD11c(+)CD4(+) dendritic cells whereas
      CD11c(+)CD8alpha(+) dendritic cells were not altered. Collectively, these data
      demonstrate the induction of autoimmunity by specific in vivo expansion of
      CD4(+)CD62L(low) cells and indicate that CD4(+)CD62L(low) effector T cells and
      CD11c(+)CD4(+) dendritic cells may be attractive targets for immune interventions
      to treat autoimmune diseases.

PMID- 16982874
TI  - The effects of age, thymectomy, and HIV Infection on alpha and beta TCR excision
      circles in naive T cells.
AB  - Due to homeostasis total naive T cell numbers remain fairly constant over life
      despite a gradual involution of the thymus. The contribution of the thymus to
      maintaining naive T cell pools is typically measured with TCR excision circles
      (TRECs) that are formed in thymocytes. The mechanisms underlying thymic
      involution are poorly understood. Some data suggest that thymocytes undergo fewer
      divisions in old (small) than young (large) thymi, and other data suggest that
      the number of TRECs per thymocyte is independent of age. If thymic involution
      were associated with a decreased number of divisions of the thymocytes, this
      would markedly complicate the interpretation of TREC data. To study this we
      develop a mathematical model in which the division rate of thymocytes decreases
      with increasing age. We describe the dilution of TRECs formed during the
      arrangement of both chains of the TCR by division of thymocytes, recent thymic
      emigrants, and mature naive T cells. The model behavior is complicated as TREC
      contents in naive T cells can increase with age due to decreased dilution in the
      thymus. Because our model is consistent with current data on the effects of age
      and thymectomy on TRECs in peripheral T cells, we conclude that aging may well
      affect thymocyte division, which markedly complicates the interpretation of TREC
      data. It is possible, but more difficult, to let the model be consistent with the
      rapid changes in alpha and beta TRECs observed shortly after HIV infection.

PMID- 16982876
TI  - Host-derived Langerhans cells persist after MHC-matched allografting independent
      of donor T cells and critically influence the alloresponses mediated by donor
      lymphocyte infusions.
AB  - Mouse models of minor histocompatibility Ag-mismatched bone marrow
      transplantation were used to study donor dendritic cell (DC) reconstitution after
      conditioning, variables influencing the persistence of residual host DCs in
      different compartments, their phenotype, and their role in governing donor
      lymphocyte infusion (DLI)-mediated alloresponses. Reconstitution of all splenic
      DC subsets occurred rapidly after bone marrow transplantation and before T cell
      reconstitution. However, in contrast to MHC-mismatched chimeras, residual host
      derived DCs persisted in the cutaneous lymph nodes (CLNs) of MHC-matched chimeras
      despite the presence or addition of donor T cells to the graft. The phenotype of
      these residual host-derived DCs in CLNs was consistent with Langerhans' cells
      (LCs). We confirmed their skin origin and found near-complete preservation of
      host-derived LCs in the skin. Host-derived LCs retained their ability to
      continuously traffic to the CLNs, expressed homogeneously increased levels of
      costimulatory molecules, and could capture and carry epicutaneously applied Ags.
      To determine the role of residual host LCs in governing DLI-mediated
      alloresponses, we administered DLI alone or after topical application of the TLR7
      ligand imiquimod, which is known to enhance the LC emigration from the skin. DLI
      administration resulted in a decrease in host-derived DCs in the CLNs and
      increased recruitment of donor-derived DCs to the skin, whereas imiquimod
      augmented their alloreactivity. These results suggest uniqueness of the MHC
      matched setting in relation to the persistence of host-derived DCs in the skin
      and points to a previously unrecognized role of host-derived LCs in the induction
      of DLI-mediated graft-vs-host alloresponses.

PMID- 16982875
TI  - A large T cell invagination with CD2 enrichment resets receptor engagement in the
      immunological synapse.
AB  - T cell activation is driven by the TCR and complemented by costimulation. We have
      studied the dynamics of ligand-engagement of the costimulatory receptor CD2 in T
      cell/APC couples. Thousands of ligand-engaged CD2 molecules were included in a
      large T cell invagination at the center of the cellular interface within 1 min of
      cell couple formation. The structure and regulation of this invagination shared
      numerous features with phagocytosis and macropinocytosis. Three observations
      further characterize the invagination and the inclusion of CD2: 1) numerous
      ligand-engaged receptors were enriched in and internalized through the T cell
      invagination, none as prominently as CD2; 2) dissolution of the T cell
      invagination and CD2 engagement were required for effective proximal T cell
      signaling; and 3) the T cell invagination was uniquely sensitive to the affinity
      of the TCR for peptide-MHC. Based on this characterization, we speculate that the
      T cell invagination, aided by CD2 enrichment, internalizes parts of the TCR
      signaling machinery to reset T cell signaling upon agonist-mediated, stable APC
      contact.

PMID- 16982877
TI  - Early exposure to IL-4 stabilizes IL-4 mRNA in CD4+ T cells via RNA-binding
      protein HuR.
AB  - The mechanisms regulating IL-4 mRNA stability in differentiated T cells are not
      known. We found that early exposure of CD4+ T cells to endogenous IL-4 increased
      IL-4 mRNA stability. This effect of IL-4 was mediated by the RNA-binding protein
      HuR. IL-4 mRNA interacted with HuR and the dominant binding site was shown within
      the coding region of IL-4 mRNA. Exposure of CD4+ T cells to IL-4 had no effects
      on HuR expression or subcellular localization, but triggered HuR binding to IL-4
      mRNA. Thus, IL-4 plays a positive role in maintaining IL-4 mRNA stability in CD4+
      T cells via a HuR-mediated mechanism.

PMID- 16982878
TI  - Regulatory role of gammadelta T cells in the recruitment of CD4+ and CD8+ T cells
      to lung and subsequent pulmonary fibrosis.
AB  - The mechanisms by which T cells accumulate in the lungs of patients with
      pulmonary fibrosis are poorly understood. Because the lung is continually exposed
      to microbial agents from the environment, we repeatedly exposed C57BL/6 mice to
      the ubiquitous microorganism, Bacillus subtilis, to determine whether chronic
      exposure to an inhaled microorganism could lead to T cell accumulation in the
      lungs and subsequent pulmonary fibrosis. C57BL/6 mice repeatedly treated with B.
      subtilis for 4 consecutive weeks developed a 33-fold increase in the number of
      CD4+ T cells and a 354-fold increase in gammadelta T cells in the lung. The
      gammadelta T cells consisted almost entirely of Vgamma6/Vdelta1+ cells, a murine
      subset bearing an invariant TCR the function of which is still unknown. Treatment
      of C57BL/6 mice with heat-killed vs live B. subtilis resulted in a 2-fold
      increase in the number of CD4+ T cells in the lung but no expansion of gammadelta
      T cells indicating that gammadelta cells accumulate in response to live
      microorganisms. In addition, mice treated with heat-killed B. subtilis developed
      significantly increased pulmonary fibrosis compared with mice treated with the
      live microorganism. Mice deficient in Vgamma6/Vdelta1+ T cells when treated with
      B. subtilis had a 231-fold increase in lung CD4+ T cells and significantly
      increased collagen deposition compared with wild-type C57BL/6 mice, consistent
      with an immunoregulatory role for the Vgamma6/Vdelta1 T cell subset. These
      findings indicate that chronic inhalation of B. subtilis can result in T cell
      accumulation in the lung and fibrosis, constituting a new model of immune
      mediated pulmonary fibrosis.

PMID- 16982879
TI  - Induction of C3 and CCL2 by C3a in keratinocytes: a novel autocrine amplification
      loop of inflammatory skin reactions.
AB  - The complement fragment-3a (C3a) acts via a G protein-coupled C3aR and is of
      importance in allergic and inflammatory diseases. Recent studies suggest the
      presence of complement proteins in the epidermal compartment and synthesis of
      some of these proteins (C3, factor B, and factor H) by human primary
      keratinocytes (KCs) during inflammation. However, expression of C3aR and its role
      in human KCs is not elucidated thus far. In this study, we demonstrate the
      expression of C3aR on KCs as detected by quantitative real-time RT-PCR and flow
      cytometry. IFN-gamma and IFN-alpha strongly up-regulated the surface expression
      of C3aR on KCs among all other cytokines tested. After up-regulation of C3aR by
      IFN-gamma and IFN-alpha, we observed the induction of five genes (CCL2, CCL5,
      CXCL8, CXCL10, and C3) after stimulation of KCs with C3a in microarray analysis.
      We confirmed the induction of C3 and CCL2 at RNA and protein levels. Furthermore,
      incubation of C3 with skin mast cells tryptase resulted in the generation of C3
      fragments with C3a activity. In conclusion, our data illustrate that epidermal
      KCs express functional C3aR. The increases of C3 and CCL2 synthesis by C3a and C3
      activation by skin mast cell tryptase delineates a novel amplification loop of
      complement activation and inflammatory responses that may influence the
      pathogenesis of allergic/inflammatory skin diseases.

PMID- 16982880
TI  - Cell-autonomous CCL5 transcription by memory CD8 T cells is regulated by IL-4.
AB  - Immunological memory is associated with the display of improved effector
      functions. The maintenance by CD8 memory cells of high levels of untranslated
      CCL5 mRNA allows these cells to immediately secrete this chemokine upon Ag
      stimulation. Untranslated mRNA storage is a newly described process supporting
      the immediate display of an effector function by memory lymphocytes. We have
      tested the capacity of different cytokines to regulate the memorization of CCL5
      by memory CD8 T cells. We found that IL-4 treatment of murine CD8 T cells impairs
      immediate CCL5 secretion capacity by inhibiting CCL5 mRNA transcription through a
      STAT6-dependent pathway. The inhibition by IL-4 is reversible, as memory CD8 T
      cells reconstitute their CCL5 mRNA stores and reacquire their immediate CCL5
      secretion capacity when IL-4 is withdrawn. This recovery is cell autonomous
      because it proceeds in culture medium in the absence of exogenous growth factors,
      suggesting that CCL5 expression by memory CD8 T cells is a default process.
      Overall, these results indicate that the expression of CCL5 is an intrinsic
      property acquired by memory CD8 T cells that is regulated by environmental
      factors.

PMID- 16982881
TI  - Augmented IL-7 signaling during viral infection drives greater expansion of
      effector T cells but does not enhance memory.
AB  - IL-7 signals are crucial for the survival of naive and memory T cells, and the IL
      7R is expressed on the surface of these cells. Following viral infection, the IL
      7R is expressed on only a subset of effector CD8 T cells, and has been
      demonstrated to be important for the survival of these memory precursors. IL-7
      message levels remain relatively constant during the T cell response to
      lymphocytic choriomeningitis virus, but a short-lived burst of GM-CSF is observed
      soon after infection. Retroviral expression of a chimeric GM-CSF/IL-7R, in which
      binding of GM-CSF by T cells leads to IL-7 signaling, allows for the delivery of
      an IL-7 signal in all effector T cells expressing the receptor. In mice infected
      with lymphocytic choriomeningitis virus, CD8 and CD4 T cells transduced with this
      chimeric receptor underwent an enhanced proliferative response compared with
      untransduced populations in the same host. Similarly, TCR transgenic CD8 cells
      expressing the chimeric receptor produced higher effector numbers during the peak
      of the T cell response to infection. Surprisingly, the enhanced proliferation did
      not lead to higher memory numbers, as the subsequent contraction phase was more
      pronounced in the transduced cell populations. These findings demonstrate that
      artificial IL-7 signaling during an infection leads to significantly increased Ag
      specific effector T cell numbers, but does not result in increased numbers of
      memory progeny. The extent of contraction may be dictated by intrinsic factors
      related to the number of prior cell divisions.

PMID- 16982882
TI  - Functional dichotomy between OX40 and 4-1BB in modulating effector CD8 T cell
      responses.
AB  - Members of the TNFR family are thought to deliver costimulatory signals to T
      cells and modulate their function and survival. In this study, we compare the
      role of two closely related TNFR family molecules, OX40 and 4-1BB, in generating
      effector CD8 T cells to Ag delivered by adenovirus. OX40 and 4-1BB were both
      induced on responding naive CD8 T cells, but 4-1BB exhibited faster and more
      sustained kinetics than OX40. OX40-deficient CD8 T cells initially expanded
      normally; however, their accumulation and survival at late times in the primary
      response was significantly impaired. In contrast, 4-1BB-deficient CD8 T cells
      displayed hyperresponsiveness, expanding more than wild-type cells. The 4-1BB
      deficient CD8 T cells also showed enhanced maturation attributes, whereas OX40
      deficient CD8 T cells had multiple defects in the expression of effector cell
      surface markers, the synthesis of cytokines, and in cytotoxic activity. These
      results suggest that, in contrast to current ideas, OX40 and 4-1BB can have a
      clear functional dichotomy in modulating effector CD8 T cell responses. OX40 can
      positively regulate effector function and late accumulation/survival, whereas 4
      1BB can initially operate in a negative manner to limit primary CD8 responses.

PMID- 16982883
TI  - CpG DNA activates survival in murine macrophages through TLR9 and the
      phosphatidylinositol 3-kinase-Akt pathway.
AB  - Bacterial CpG-containing (CpG) DNA promotes survival of murine macrophages and
      triggers production of proinflammatory mediators. The CpG DNA-induced
      inflammatory response is mediated via TLR9, whereas a recent study reported that
      activation of the Akt prosurvival pathway occurs via DNA-dependent protein kinase
      (DNA-PK) and independently of TLR9. We show, in this study, that Akt activation
      and survival of murine bone marrow-derived macrophages (BMM) triggered by CpG
      containing phosphodiester oligodeoxynucleotides or CpG-containing
      phosphorothioate oligodeoxynucleotides was completely dependent on TLR9. In
      addition, survival triggered by CpG-containing phosphodiester
      oligodeoxynucleotides was not compromised in BMM from SCID mice that express a
      catalytically inactive form of DNA-PK. CpG DNA-induced survival of BMM was
      inhibited by the PI3K inhibitor, LY294002, but not by the MEK1/2 inhibitor,
      PD98059. The effect of LY294002 was specific to survival, because treatment of
      BMM with LY294002 affected CpG DNA-induced TNF-alpha production only modestly.
      Therefore, CpG DNA activates macrophage survival via TLR9 and the PI3K-Akt
      pathway and independently of DNA-PK and MEK-ERK.

PMID- 16982884
TI  - B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated
      autoantigen presentation.
AB  - Both B cells and dendritic cells (DCs) have been implicated as autoantigen
      presenting cells in the activation of self-reactive T cells. However, most self
      proteins are ubiquitously and/or developmentally expressed, making it difficult
      to determine the source and the exposure of autoantigens to APCs in a controlled
      manner. In this study, we have used an Ig transgenic mouse model to examine the
      mechanisms by which B cells and other APCs acquire and present lupus autoantigens
      in vivo. Targeting a lupus autoantigen, the small nuclear ribonucleoprotein
      particle D protein, to the BCR activates autoreactive T cells in the periphery.
      Our in vivo studies demonstrate that autoantigen-specific B cells, when present
      in the repertoire, are the first subset of APCs to capture and present self
      proteins for activating T cells. Thereafter, DCs acquire self-Ag and become
      effective APCs for stimulating the same subsets of autoreactive T cells. This
      mechanism provides one explanation of how early steps in autoimmunity can focus
      responses, via BCR, at a small group of self-proteins among the total milieu of
      intracellular self-proteins. Subsequently, DCs and other professional APCs may
      then amplify and perpetuate the autoimmune T cell response.

PMID- 16982885
TI  - The majority of human peripheral blood CD4+CD25highFoxp3+ regulatory T cells bear
      functional skin-homing receptors.
AB  - CD4+CD25+ T regulatory cells (Treg) are thought to be important in the peripheral
      tolerance. Recent evidence suggests that human peripheral blood CD4+CD25+ T cells
      are heterogeneous and contain both CD4+CD25(high) T cells with potent regulatory
      activity and many more CD4+CD25(low/med) nonregulatory T cells. In this study, we
      found that virtually all peripheral blood CD4+CD25(high)Foxp3+ Treg expressed
      high levels of the chemokine receptor CCR4. In addition, 80% of Treg expressed
      cutaneous lymphocyte Ag (CLA) and 73% expressed CCR6. These molecules were
      functional, as CLA+ Treg showed CD62E ligand activity and demonstrable
      chemotactic responses to the CCR4 ligands CCL22 and CCL17 and to the CCR6 ligand
      CCL20. The phenotype and chemotactic response of these Treg were significantly
      different from those of CD4+CD25(med) nonregulatory T cells. We further
      demonstrated that blood CLA+ Treg inhibited CD4+CD25- T cell proliferation
      induced by anti-CD3. Based on homing receptor profile, CLA+ Treg should enter
      normal skin. We next isolated CD4+CD25(high) T cells directly from normal human
      skin; these cells suppressed proliferation of skin CD4+CD25- T cells. Therefore,
      the majority of true circulating Treg express functional skin-homing receptors,
      and human Treg may regulate local immune responses in normal human skin.

PMID- 16982886
TI  - Ligation of CD80 is critical for high-level CD25 expression on CD8+ T
      lymphocytes.
AB  - CD80 and CD86 have been shown to play a critical role in the optimal activation
      of T cells. Although these two molecules bind the same ligand, CD28, the question
      of whether CD80 and CD86 provide unique signals or serve redundant roles remains
      controversial. Previous studies have suggested that CD80 binding to CD28 may be
      superior to CD86 for the activation of naive CD8+ T cells. This study provides a
      potential mechanism to explain these observations. Our study demonstrates a
      previously unappreciated role for CD80, its superiority over CD86 in promoting
      CD25 expression, increasing both the number of cells that express CD25 and the
      level expressed on a per cell basis. These findings provide new insights into the
      role of CD80 vs CD86 and have important implications for the design of vaccines
      and immunotherapeutics aimed at the generation of a robust CD8+ T cell response
      in vivo.

PMID- 16982887
TI  - A novel role for viral-defective interfering particles in enhancing dendritic
      cell maturation.
AB  - Dendritic cell (DC) maturation is a crucial event in the development of adaptive
      immune responses that confer long-lasting protection against reinfection with the
      same virus. Sendai virus strain Cantell has a particularly strong ability to
      mature DCs independently of type I IFNs and TLR signaling, currently the best
      described pathways for the induction of DC maturation. In this study, we
      demonstrate that defective-interfering (DI) particles present in Sendai virus
      Cantell stocks are required for its robust DC maturation ability. DI particles
      contain incomplete genomes that are unable to replicate unless the viral
      polymerase is supplied by coinfection with complete virus. Accordingly, the
      improvement in the virus-induced maturation of DCs provided by DI particles
      requires standard virus coinfection and likely results from increased production
      of dsRNA replication intermediaries. This unique ability of DI particles to
      stimulate DC maturation cannot be mimicked by simply increasing the dose of
      standard virus. Furthermore, viruses with weak DC maturation abilities can be
      converted into potent DC stimulators with the addition of DI particles,
      supporting a potential application for DI particles as a novel natural adjuvant
      for viral immunizations.

PMID- 16982888
TI  - Trauma-hemorrhage induces depressed splenic dendritic cell functions in mice.
AB  - Although Kupffer cell, splenic, and peritoneal macrophage functions are markedly
      altered following trauma-hemorrhage (T-H), it remains unclear whether T-H also
      affects splenic dendritic cell (sDC) functions. We hypothesized that sDC
      functions will also be compromised following T-H. Male C3H/HeN (6- to 8-wk) mice
      were randomly assigned to sham operation or T-H. T-H was induced by midline
      laparotomy and approximately 90 min of hemorrhagic shock (blood pressure 35
      mmHg), followed by fluid resuscitation (four times the shed blood volume in the
      form of Ringer's lactate). Two hours later, the mice were sacrificed; sDC were
      isolated; and the changes in their apoptosis, MHC class II expression, and
      ability to produce costimulatory cytokines and Ag presentation were measured. The
      results indicate that sDC Ag presentation capacity was significantly decreased
      and MHC class II expression was also significantly decreased following T-H.
      Moreover, LPS-induced IL-12 production and LPS- or IL-12-induced IFN-gamma
      production following T-H were significantly decreased. Thus, the markedly
      decreased MHC class II expression and cytokine (IL-12, IFN-gamma) production
      following T-H may be the cause for the depressed sDC Ag presentation under those
      conditions. This depression in Ag presentation could contribute to the host's
      enhanced susceptibility to sepsis following T-H.

PMID- 16982889
TI  - Homeostatic proliferation as an isolated variable reverses CD8+ T cell anergy and
      promotes tumor rejection.
AB  - Although recent work has suggested that lymphopenia-induced homeostatic
      proliferation may improve T cell-mediated tumor rejection, there is little direct
      evidence isolating homeostatic proliferation as an experimental variable, and the
      mechanism by which improved antitumor immunity occurs via homeostatic
      proliferation is poorly understood. An adoptive transfer model was developed in
      which tumor-specific 2C/RAG2(-/-) TCR transgenic CD8+ T cells were introduced
      either into the lymphopenic environment of RAG2(-/-) mice or into P14/RAG2(-/-)
      mice containing an irrelevant CD8+ TCR transgenic population. RAG2(-/-), but not
      P14/RAG2(-/-) recipients supported homeostatic proliferation of transferred T
      cells as well as tumor rejection. Despite absence of tumor rejection in P14/RAG2(
      /-) recipients, 2C cells did become activated, as reflected by CFSE dilution and
      CD44 up-regulation. However, these cells showed poor IFN-gamma and IL-2
      production upon restimulation, consistent with T cell anergy and similar to the
      hyporesponsiveness induced by administration of soluble peptide Ag. To determine
      whether homeostatic proliferation could uncouple T cell anergy, anergic 2C cells
      were transferred into RAG(-/-) recipients, which resulted in vigorous homeostatic
      proliferation, recovery of IL-2 production, and acquisition of the ability to
      reject tumors. Taken together, our data suggest that a major mechanism by which
      homeostatic proliferation supports tumor rejection is by maintaining and/or re
      establishing T cell responsiveness.

PMID- 16982890
TI  - STAT1-independent cell type-specific regulation of antiviral APOBEC3G by IFN
      alpha.
AB  - APOBEC3G (A3G) has broad antiviral activity against retroviruses and hepatitis B
      virus. However, the role of IFNs in regulating A3G during innate immunity has not
      been established. In this study, we show that the A3G gene is uniquely regulated
      by IFNs in a cell type-dependent manner. A3G was up-regulated by IFN-alpha in
      liver cells and macrophages, but not in T lymphoid cells or epithelial 293T
      cells. In contrast, other IFN-alpha-stimulated genes such as dsRNA-activated
      protein kinase were induced in all these cells, suggesting additional cellular
      factors may regulate IFN-alpha-induced A3G expression. Consistent with this idea,
      IFN-alpha-mediated induction of A3G, but not other IFN-alpha-stimulated genes,
      was potently inhibited by the drug Rottlerin, through a mechanism independent of
      STAT1 activation. The canonical IFN-alpha-mediated pathway of gene transcription
      requires both STAT1 and STAT2. Surprisingly, induction of A3G was STAT1
      independent, but STAT2 dependent in liver cells. However, STAT1 signaling was
      functional and required for IFN-gamma induction of A3G in these cells. Our
      results indicate that A3G may participate in antiviral cellular defenses through
      a novel IFN-mediated signaling pathway.

PMID- 16982891
TI  - Intracellular protein modification associated with altered T cell functions in
      autoimmunity.
AB  - Posttranslational protein modifications influence a number of immunologic
      responses ranging from intracellular signaling to protein processing and
      presentation. One such modification, termed isoaspartyl (isoAsp), is the
      spontaneous nonenzymatic modification of aspartic acid residues occurring at
      physiologic pH and temperature. In this study, we have examined the intracellular
      levels of isoAsp residues in self-proteins from MRL(+/+), MRL/lpr, and NZB/W F(1)
      mouse strains compared with nonautoimmune B10.BR mice. In contrast to control
      B10.BR or NZB/W mice, the isoAsp content in MRL autoimmune mice increased and
      accumulated with age in erythrocytes, brain, kidney, and T lymphocytes. Moreover,
      T cells that hyperproliferate to antigenic stimulation in MRL mice also have
      elevated intracellular isoAsp protein content. Protein l-isoaspartate O
      methyltransferase activity, a repair enzyme for isoAsp residues in vivo, remains
      stable with age in all strains of mice. These studies demonstrate a role for the
      accumulation of intracellular isoAsp proteins associated with T cell
      proliferative defects of MRL autoimmune mice.

PMID- 16982892
TI  - Rac1 negatively regulates lipopolysaccharide-induced IL-23 p19 expression in
      human macrophages and dendritic cells and NF-kappaB p65 trans activation plays a
      novel role.
AB  - IL-23 is a heterodimeric cytokine composed of a unique p19 subunit and of a p40
      subunit that is also common to IL-12. We defined the distinct signaling
      mechanisms that regulate the LPS-mediated induction of IL-23 p19 and p40 in human
      macrophages and dendritic cells. We found that the overexpression of dominant
      negative Rac1 (N17Rac1) enhanced LPS-induced IL-23 p19 expression but did not
      alter p40 expression or IL-12 p70 production in PMA-treated THP-1 macrophages and
      in human monocyte-derived dendritic cells. Although the inhibition of either p38
      MAPK or JNK enhanced LPS-induced p19 expression, N17Rac1 did not influence either
      p38 MAPK or JNK activation. By contrast, N17Rac1 augmented both NF-kappaB gene
      expression and p65 trans activation stimulated by LPS without affecting the
      degradation of IkappaB-alpha or DNA binding to NF-kappaB. Furthermore, small
      interference RNA of NF-kappaB p65 attenuated cellular amounts of p65 and
      suppressed LPS-induced p19 expression but did not affect p40 expression. Our
      findings indicate that Rac1 negatively controls LPS-induced IL-23 p19 expression
      through an NF-kappaB p65 trans activation-dependent, IkappaB-independent pathway
      and that NF-kappaB p65 regulates LPS-induced IL-23 p19, but not p40, expression,
      which causes differences in the control of IL-23 p19 and p40 expression by Rac1.

PMID- 16982893
TI  - CD25+CD4+ regulatory T cells and memory T cells prevent lymphopenia-induced
      proliferation of naive T cells in transient states of lymphopenia.
AB  - Lymphopenia has been associated with autoimmune pathology and it has been
      suggested that lymphopenia-induced proliferation of naive T cells may be
      responsible for the development of immune pathology. In this study we demonstrate
      that lymphopenia-induced proliferation is restricted to conditions of extreme
      lymphopenia, because neither naive nor memory T cells transferred into T cell
      depleted hosts proliferate unless the depletion exceeds 90% of the peripheral
      repertoire. Memory CD4 T cells as well as regulatory CD4 T cells proved to be
      relatively resistant to depletion regimes, and both subsets restrict the
      expansion and phenotypic conversion of naive T cells by an IL-7R-dependent
      mechanism. It therefore seems unlikely that lymphopenia-induced proliferation of
      peripheral T cells causes deleterious side effects that result in immune
      pathology in states of partial and transient lymphopenia.

PMID- 16982894
TI  - PKB rescues calcineurin/NFAT-induced arrest of Rag expression and pre-T cell
      differentiation.
AB  - Protein kinase B (PKB), an Ag receptor activated serine-threonine kinase,
      controls various cellular processes including proliferation and survival.
      However, PKB function in thymocyte development is still unclear. We report PKB as
      an important negative regulator of the calcineurin (CN)-regulated transcription
      factor NFAT in early T cell differentiation. Expression of a hyperactive version
      of CN induces a profound block at the CD25+CD44- double-negative (DN) 3 stage of
      T cell development. We correlate this arrest with up-regulation of Bcl-2, CD2,
      CD5, and CD27 proteins and constitutive activation of NFAT but a severe
      impairment of Rag1, Rag2, and intracellular TCR-beta as well as intracellular TCR
      gammadelta protein expression. Intriguingly, simultaneous expression of active
      myristoylated PKB inhibits nuclear NFAT activity, restores Rag activity, and
      enables DN3 cells to undergo normal differentiation and expansion. A correlation
      between the loss of NFAT activity and Rag1 and Rag2 expression is also found in
      myristoylated PKB-induced CD4+ lymphoma cells. Furthermore, ectopic expression of
      NFAT inhibits Rag2 promoter activity in EL4 cells, and in vivo binding of NFATc1
      to the Rag1 and Rag2 promoter and cis-acting transcription regulatory elements is
      verified by chromatin immunoprecipitation analysis. The regulation of CN/NFAT
      signaling by PKB may thus control receptor regulated changes in Rag expression
      and constitute a signaling pathway important for differentiation processes in the
      thymus and periphery.

PMID- 16982895
TI  - Structural characterization of mycobacterial phosphatidylinositol mannoside
      binding to mouse CD1d.
AB  - Mycobacterial phosphatidylinositol tetramannosides (PIM4) are agonists for a
      distinct population of invariant human (Valpha24) and mouse (Valpha14) NKT cells,
      when presented by CD1d. We determined the crystal structure at 2.6-A resolution
      of mouse CD1d bound to a synthetic dipalmitoyl-PIM2. Natural PIM2, which differs
      in its fatty acid composition is a biosynthetic precursor of PIM4, PIM6,
      lipomannan, and lipoarabinomannan. The PIM2 headgroup (inositol-dimannoside) is
      the most complex to date among all the crystallized CD1d ligands and is
      remarkably ordered in the CD1d binding groove. A specific hydrogen-bonding
      network between PIM2 and CD1d orients the headgroup in the center of the binding
      groove and above the A' pocket. A central cluster of hydrophilic CD1d residues
      (Asp(153), Thr(156), Ser(76), Arg(79)) interacts with the phosphate, inositol,
      and alpha1-alpha6-linked mannose of the headgroup, whereas additional specificity
      for the alpha1- and alpha2-linked mannose is conferred by Thr(159). The
      additional two mannoses in PIM4, relative to PIM2, are located at the distal 6'
      carbon of the alpha1-alpha6-linked mannose and would project away from the CD1d
      binding groove for interaction with the TCR. Compared with other CD1d
      sphingolipid structures, PIM2 has an increased number of polar interactions
      between its headgroup and CD1, but reduced specificity for the diacylglycerol
      backbone. Thus, novel NKT cell agonists can be designed that focus on
      substitutions of the headgroup rather than on reducing lipid chain length, as in
      OCH and PBS-25, two potent variants of the highly stimulatory invariant NKT cell
      agonist alpha-galactosylceramide.

PMID- 16982896
TI  - Repression of IFN-gamma induction of class II transactivator: a role for
      PRDM1/Blimp-1 in regulation of cytokine signaling.
AB  - MHC class II is expressed in restricted lineages and is modulated in response to
      pathogens and inflammatory stimuli. This expression is controlled by MHC CIITA,
      which is transcribed from multiple promoters. Although factors required for
      induction of CIITA are well characterized, less is known about the mechanisms
      leading to repression of this gene. During plasma cell differentiation, B
      lymphocyte-induced maturation protein-1 (PRDM1/Blimp-1) represses promoter (p)III
      of CIITA, responsible for constitutive expression in B cells. pIV is inducible by
      IFN-gamma in epithelia, macrophages and B cells. An IFN regulatory factor-element
      (IRF-E) in CIITA-pIV, which is bound by IRF-1 and IRF-2, is necessary for this
      response. This site matches the PRDM1/Blimp-1 consensus binding site, and
      PRDM1/Blimp-1 is expressed in cell lineages in which this promoter is operative.
      We, therefore, investigated whether PRDM1 regulates CIITA-pIV and found that
      PRDM1 bound to CIITA-pIV in vivo and the IRF-E in vitro. PRDM1 repressed IFN
      gamma-mediated induction of a CIITA-pIV luciferase reporter in a fashion
      dependent on an intact consensus sequence and competes with IRF-1/IRF-2 for
      binding to the IRF-E and promoter activation. In human myeloma cell lines that
      express IRFs, PRDM1 occupancy of CIITA-pIV was associated with resistance to IFN
      gamma stimulation, while short interfering RNA knockdown of PRDM1 led to up
      regulation of CIITA. Our data indicate that PRDM1 is a repressor of CIITA-pIV,
      identifying a target of particular relevance to macrophages and epithelia. These
      findings support a model in which PRDM1/Blimp-1 can modulate the cellular
      response to IFN-gamma by competing with IRF-1/IRF-2 dependent activation of
      target promoters.

PMID- 16982897
TI  - Characterization of a novel C-type lectin, Bombyx mori multibinding protein, from
      the B. mori hemolymph: mechanism of wide-range microorganism recognition and role
      in immunity.
AB  - To investigate the system used by insects to recognize invading microorganisms,
      we examined proteins from the larval hemolymph of Bombyx mori that bind to the
      cell surface of microorganisms. Two hemolymph proteins that bound to the cell
      surfaces of Micrococcus luteus and Saccharomyces cerevisiae were shown to be
      identical. This protein bound to all 11 microorganisms examined-5 Gram-negative
      bacteria, 3 Gram-positive bacteria, and 3 yeasts-and was consequently designated
      B. mori multibinding protein (BmMBP). The sequence of the cDNA encoding BmMBP
      revealed that it was a C-type lectin with two dissimilar carbohydrate-recognition
      domains (CRD1 and CRD2) distantly related to known insect C-type lectins. CRD1
      and CRD2 were prepared as recombinant proteins and their binding properties were
      investigated using inhibition assays. Each domain had wide, dissimilar binding
      spectra to sugars. These properties enable BmMBP to bind to two sites on a
      microorganism, facilitating high-affinity binding to many types of
      microorganisms. The dissociation constants of BmMBP with M. luteus cells and S.
      cerevisiae were 1.23 x 10(-8) and 1.00 x 10(-11) M, respectively. rBmMBP
      triggered the aggregation of hemocytes from B. mori larvae in vitro and
      microorganisms recognized by BmMBP were surrounded by aggregated hemocytes in
      vivo, forming a nodule, which is the typical cellular reaction in insect immune
      responses. These observations suggest that BmMBP functions as a trigger for the
      nodule reaction and that the multirecognition characteristic of BmMBP plays an
      important role in the early stages of infection by a variety of microorganisms.

PMID- 16982898
TI  - Molecular mechanisms for transcriptional regulation of human high-affinity IgE
      receptor beta-chain gene induced by GM-CSF.
AB  - The beta-chain of the high-affinity receptor for IgE (FcepsilonRI) plays an
      important role in regulating activation of FcepsilonRI-expressing cells such as
      mast cells in allergic reactions. We already reported that the transcription
      factor myeloid zinc finger (MZF) 1 which formed a high m.w. complex including
      four and a half LIM-only protein (FHL)3 in the nucleus repressed human beta-chain
      gene expression through an element in the fourth intron. We also found that GM
      CSF induced expression of MZF-1 and nuclear translocation of FHL3. We screened a
      human cDNA library and identified NFY which was reported to bind histone
      deacetylases (HDACs) as a constituent of the complex. The C-subunit of NFY was
      demonstrated to form a ternary complex with MZF-1/FHL3 and interact with a beta
      chain gene region including the element in the fourth intron. HDAC1 and HDAC2
      were also shown to interact with the fourth intron region of the beta-chain gene.
      In a human mast cell line HMC-1 cultured with GM-CSF, both beta-chain expression
      and acetylation of histones interacting with the fourth intron region of the beta
      chain gene were decreased. Collectively, these results indicated that HDACs,
      which were recruited to the beta-chain gene through the element in the fourth
      intron by MZF-1/FHL3/NFY, repressed beta-chain gene transcription by
      deacetylation of histones in the presence of GM-CSF. These mechanisms will be
      involved in not only the cell type-specific repression of beta-chain gene
      expression in differentiating hemopoietic cells but also the repression of beta
      chain gene expression in the peripheral cells under specific circumstances.

PMID- 16982899
TI  - Identification of susceptibility loci for skin disease in a murine psoriasis
      model.
AB  - Psoriasis is a frequently occurring inflammatory skin disease characterized by
      thickened erythematous skin that is covered with silvery scales. It is a complex
      genetic disease with both heritable and environmental factors contributing to
      onset and severity. The CD18 hypomorphic PL/J mouse reveals reduced expression of
      the common chain of beta(2) integrins (CD11/CD18) and spontaneously develops a
      skin disease that closely resembles human psoriasis. In contrast, CD18
      hypomorphic C57BL/6J mice do not demonstrate this phenotype. In this study, we
      have performed a genome-wide scan to identify loci involved in psoriasiform
      dermatitis under the condition of low CD18 expression. Backcross analysis of a
      segregating cross between susceptible CD18 hypomorphic PL/J mice and the
      resistant CD18 hypomorphic C57BL/6J strain was performed. A genome-wide linkage
      analysis of 94 phenotypically extreme mice of the backcross was undertaken.
      Thereafter, a complementary analysis of the regions of interest from the genome
      wide screen was done using higher marker density and further mice. We found two
      loci on chromosome 10 that were significantly linked to the disease and
      interacted in an additive fashion in its development. In addition, a locus on
      chromosome 6 that promoted earlier onset of the disease was identified in the
      most severely affected mice. For the first time, we have identified genetic
      regions associated with psoriasis in a mouse model resembling human psoriasis.
      The identification of gene regions associated with psoriasis in this mouse model
      might contribute to the understanding of genetic causes of psoriasis in patients
      and pathological mechanisms involved in development of disease.

PMID- 16982900
TI  - MHC class II molecules control murine B cell responsiveness to lipopolysaccharide
      stimulation.
AB  - LPS is a strong stimulator of the innate immune system and inducer of B
      lymphocyte activation. Two TLRs, TLR4 and RP105 (CD180), have been identified as
      mediators of LPS signaling in murine B cells, but little is known about genetic
      factors that are able to control LPS-induced cell activation. We performed a
      mouse genome-wide screen that aside from identifying a controlling locus mapping
      in the TLR4 region (logarithm of odds score, 2.77), also revealed that a locus
      closely linked to the MHC region (logarithm of odds score, 3.4) governed B cell
      responsiveness to LPS stimulation. Using purified B cells obtained from MHC
      congenic strains, we demonstrated that the MHC(b) haplotype is accountable for
      higher cell activation, cell proliferation, and IgM secretion, after LPS
      stimulation, when compared with the MHC(d) haplotype. Furthermore, B cells from
      MHC class II(-/-) mice displayed enhanced activation and proliferation in
      response to LPS. In addition, we showed that the MHC haplotype partially controls
      expression of RP105 (a LPS receptor molecule), following a pattern that resembles
      the LPS responsiveness phenotype. Together, our results strongly suggest that
      murine MHC class II molecules play a role in constraining the B cell response to
      LPS and that genetic variation at the MHC locus is an important component in
      controlling B cell responsiveness to LPS stimulation. This work raises the
      possibility that constraining of B cell responsiveness by MHC class II molecules
      may represent a functional interaction between adaptive and innate immune
      systems.

PMID- 16982901
TI  - Restoration of natural IgM production from liver B cells by exogenous IL-18
      improves the survival of burn-injured mice infected with Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is the most common bacterium of postburn infection. In the
      present study we investigated the immune mechanism of susceptibility to this type
      of postburn infection and also examined the efficacy of IL-18 treatment. C57BL/6
      mice were challenged with P. aeruginosa on day 7 after burn injury. Although the
      burn-injured mice showed a poor survival rate after bacterial challenge, they
      retained their IFN-gamma production. The burned mice showed lower serum IgM
      levels and a poor IgM response following P. aeruginosa challenge in comparison
      with the sham mice, whereas IL-18 treatment after burn injury (alternate day
      injections for 1 wk) greatly improved the serum IgM levels, which are P.
      aeruginosa-independent natural IgM before bacterial challenge, thereby increasing
      the survival rate after the challenge. IL-18 treatment also induced specific IgM
      to P. aeruginosa in the sera 5 days after bacterial challenge in the burned mice.
      Interestingly, CD43(+)CD5(-)CD23(-)B220(dim) cells, namely B-1b cells, increased
      in the liver after the IL-18 treatment and were found to actively produce IgM in
      vitro without any additional stimulation. Furthermore, the IL-18 treatment up
      regulated the neutrophil count and the C3a levels in the blood as a result of the
      increased IgM level, which may thus play a critical role in the opsonization and
      elimination of any invading bacteria. IL-18 treatment for the burned mice and
      their resultant natural IgM production were thus found to strengthen the host
      defense against P. aeruginosa infection.

PMID- 16982902
TI  - Inhibition of IL-2 induced IL-10 production as a principle of phase-specific
      immunotherapy.
AB  - Leishmania donovani, a protozoan parasite, inflicts a fatal disease, visceral
      leishmaniasis. The suppression of antileishmanial T cell responses that
      characterizes the disease was proposed to be due to deficiency of a T cell growth
      factor, IL-2. We demonstrate that during the first week after L. donovani
      infection, IL-2 induces IL-10 that suppresses the host-protective functions of T
      cells 14 days after infection. The observed suppression is concurrent with
      increased CD4+ glucocorticoid-induced TNF receptor+ T cells and Foxp3 expression
      in BALB/c mice, implicating IL-2-dependent regulatory T cell control of
      antileishmanial immune responses. Indeed, IL-2 and IL-10 neutralization at
      different time points after the infection demonstrates their distinct roles at
      the priming and effector phases, respectively, and establishes kinetic modulation
      of ongoing immune responses as a principle of a rational, phase-specific
      immunotherapy.

PMID- 16982903
TI  - Fatal recall responses mediated by CD8 T cells during intracellular bacterial
      challenge infection.
AB  - The roles(s) of CD8 T cells during infections by intracellular bacteria that
      reside in host cell endocytic compartments are not well understood. Our previous
      studies in a mouse model of human monocytotropic ehrlichiosis indicated that CD8
      T cells are not essential for immunity. However, we have observed an unexpected
      role for these cells during challenge infection. Although immunocompetent mice
      cleared a primary low-dose (nonfatal) Ixodes ovatus ehrlichia infection, a
      secondary low-dose challenge infection resulted in fatal disease and loss of
      control of infection. The outcome was CD8-dependent, because CD8-deficient mice
      survived secondary low-dose challenge infection. Moreover, effector and/or memory
      phenotype CD8 T cells were responsible, because adoptive transfer of purified
      CD44(high) CD8 T cells to naive mice induced fatal responses following a primary
      low-dose infection. The fatal responses were perforin- and Fas ligand
      independent, and were associated with high serum concentrations of TNF-alpha and
      CCL2, and low levels of IL-10. Accordingly, blockade of either TNF-alpha or CCL2
      ameliorated fatal recall responses, and in vitro coculture of memory CD8 T cells
      and Ixodes ovatus ehrlichia-infected peritoneal exudate cells resulted in
      substantial increases in TNF-alpha and CCL2. Thus, during monocytotropic
      ehrlichiosis, inflammatory cytokine production, by CD8 T cells and/or other host
      cells, can trigger chemokine-dependent disease. These findings highlight a novel
      role for CD8 T cells, and reveal that live vaccines for intracellular bacteria
      can, under some conditions, induce undesirable consequences.

PMID- 16982904
TI  - Immunologic homeostasis during infection: coexistence of strong pulmonary cell
      mediated immunity to secondary Cryptococcus neoformans infection while the
      primary infection still persists at low levels in the lungs.
AB  - Maintenance of immunity to persistent pathogens is poorly understood. In this
      study, we used a murine model of persistent pulmonary fungal infection to study
      the ongoing cell-mediated immune response. CBA/J mice with low-level persistent
      Cryptococcus neoformans infection had CD4+ T cells of effector memory phenotype
      present in their lungs. Although unable to eliminate the primary infection to
      sterility, these mice displayed hallmarks of immunologic memory in response to
      rechallenge with C. neoformans: 1) the secondary cryptococcal challenge was
      controlled much more rapidly, 2) the inflammatory response developed and resolved
      more rapidly, 3) CD4+ T and CD8+ T cell responses were higher in magnitude, and
      4) effector cytokine production by T cells was greatly enhanced. Depletion of
      CD4+ T cells at the time of secondary challenge adversely affected clearance of
      C. neoformans from the lungs. These results demonstrate that persistent low-level
      infection with C. neoformans does not impair the cell-mediated response to the
      fungus. Although they are relatively free of overt disease, these mice can
      respond with a rapid secondary immune response if the burden of C. neoformans
      increases. These data support the concept that immunologically healthy
      individuals can maintain low numbers of cryptococci that can become a nidus for
      re-activation disease during immunodeficient states such as AIDS.

PMID- 16982905
TI  - IL-17 production is dominated by gammadelta T cells rather than CD4 T cells
      during Mycobacterium tuberculosis infection.
AB  - IL-17 is a cytokine produced by T cells in response to IL-23. Recent data support
      a new subset of CD4 Th cells distinct from Th1 or Th2 cells that produce IL-17
      and may contribute to inflammation. In this study, we demonstrate that, in naive
      mice, as well as during Mycobacterium tuberculosis infection, IL-17 production is
      primarily from gammadelta T cells and other non-CD4(+)CD8(+) cells, rather than
      CD4 T cells. The production of IL-17 by these cells is stimulated by IL-23 alone,
      and strongly induced by the cytokines, including IL-23, produced by M.
      tuberculosis-infected dendritic cells. IL-23 is present in the lungs early in
      infection and the IL-17-producing cells, such as gammadelta T cells, may
      represent a central innate protective response to pulmonary infection.

PMID- 16982906
TI  - Murine gamma-herpesvirus 68 limits naturally occurring CD4+CD25+ T regulatory
      cell activity following infection.
AB  - During microbial infections, naturally occurring CD4+CD25+ T regulatory cells can
      suppress protective host responses or they can limit pathogen-induced
      inflammatory responses. The particular role played by these cells seems to depend
      upon the infectious agent being investigated. Gamma-herpesviruses are efficacious
      pathogens which are well-known for their ability to induce lymphoproliferative
      disease and to establish latency in the host. However, no studies have
      investigated the importance of naturally occurring CD4+CD25+ T regulatory cells
      during infection with these viruses. Using the murine model of gamma-herpesvirus
      infection, murine gamma-herpesvirus 68 (gammaHV-68), we were surprised to find
      that levels of the CD4+CD25+ T regulatory cell transcript, FoxP3, continued to
      decrease as viral latency increased and as the leukocytosis phase of the disease
      progressed. Consistent with these results, the decrease in FoxP3 protein
      expression followed similar kinetics. Along with the reduced expression of this
      regulatory T cell marker, we also observed diminished CD4+CD25+ T regulatory cell
      activity in these cells isolated from gammaHV-68-infected animals. Dendritic
      cells infected in vitro with gammaHV-68 did not alter the ability of normal
      CD4+CD25+ regulatory T cells to limit the proliferation of CD4+ Th cells
      following stimulation. Taken together, these studies demonstrate a decreased
      presence and activity of CD4+CD25+ T regulatory cells during the mononucleosis
      like phase of this viral infection. These alterations in naturally occurring T
      regulatory cell function may help to explain the dysregulation of the host's
      immune response which allows the uncontrolled expansion of leukocytes as viral
      latency is established.

PMID- 16982907
TI  - Specific recognition of Candida albicans by macrophages requires galectin-3 to
      discriminate Saccharomyces cerevisiae and needs association with TLR2 for
      signaling.
AB  - Stimulation of cells of the macrophage lineage is a crucial step in the sensing
      of yeasts by the immune system. Glycans present in both Candida albicans and
      Saccharomyces cerevisiae cell walls have been shown to act as ligands for
      different receptors leading to different stimulating pathways, some of which need
      receptor co-involvement. However, among these ligand-receptor couples, none has
      been shown to discriminate the pathogenic yeast C. albicans. We explored the role
      of galectin-3, which binds C. albicans beta-1,2 mannosides. These glycans are
      specifically and prominently expressed at the surface of C. albicans but not on
      S. cerevisiae. Using a mouse cell line and galectin-3-deleted cells from knockout
      mice, we demonstrated a specific enhancement of the cellular response to C.
      albicans compared with S. cerevisiae, which depended on galectin-3 expression.
      However, galectin-3 was not required for recognition and endocytosis of yeasts.
      In contrast, using PMA-induced differentiated THP-1, we observed that the
      presence of TLR2 was required for efficient uptake and endocytosis of both C.
      albicans and S. cerevisiae. TLR2 and galectin-3, which are expressed at the level
      of phagosomes containing C. albicans, were shown to be associated in
      differentiated macrophages after incubation with this sole species. These data
      suggest that macrophages differently sense C. albicans and S. cerevisiae through
      a mechanism involving TLR2 and galectin-3, which probably associate for binding
      of ligands expressing beta-1,2 mannosides specific to the C. albicans cell wall
      surface.

PMID- 16982908
TI  - The reduced bactericidal function of complement C5-deficient murine macrophages
      is associated with defects in the synthesis and delivery of reactive oxygen
      radicals to mycobacterial phagosomes.
AB  - Complement C5-deficient (C5(-/-)) macrophages derived from B.10 congenic mice
      were found to be defective in killing intracellular Mycobacterium tuberculosis
      (MTB). They were bacteriostatic after activation with IFN-gamma alone but
      bactericidal in the combined presence of IFN-gamma and C5-derived C5a
      anaphylatoxin that was deficient among these macrophages. Reduced killing
      correlated with a decreased production of reactive oxygen species (ROS) in the
      C5(-/-) macrophages measured using fluorescent probes. Furthermore, a lack of
      colocalization of p47(phox) protein of the NADPH oxidase (phox) complex with GFP
      expressing MTB (gfpMTB) indicated a defective assembly of the phox complex on
      phagosomes. Reconstitution with C5a, a known ROS activator, enhanced the assembly
      of phox complex on the phagosomes as well as the production of ROS that inhibited
      the growth of MTB. Protein kinase C (PKC) isoforms are involved in the
      phosphorylation and translocation of p47(phox) onto bacterial phagosomes. Western
      blot analysis demonstrated a defective phosphorylation of PKC (alpha, beta,
      delta) and PKC-zeta in the cytosol of C5(-/-) macrophages compared with C5 intact
      (C5(+/+)) macrophages. Furthermore, in situ fluorescent labeling of phagosomes
      indicated that PKC-beta and PKC-zeta were the isoforms that are not
      phosphorylated in C5(-/-) macrophages. Because Fc receptor-mediated phox assembly
      was normal in both C5(-/-) and C5(+/+) macrophages, the defect in phox assembly
      around MTB phagosomes was specific to C5 deficiency. Reduced bactericidal
      function of C5(-/-) macrophages thus appears to be due to a defective assembly
      and production of ROS that prevents effective killing of intracellular MTB.

PMID- 16982909
TI  - Differential selection pressure exerted on HIV by CTL targeting identical
      epitopes but restricted by distinct HLA alleles from the same HLA supertype.
AB  - HLA diversity is seen as a major challenge to CTL vaccines against HIV. One
      current approach focuses on "promiscuous" epitopes, presented by multiple HLA
      alleles from within the same HLA supertype. However, the effectiveness of such
      supertype vaccines depends upon the functional equivalence of CTL targeting a
      particular epitope, irrespective of the restricting HLA. In this study, we
      describe the promiscuous HIV-specific CTL epitopes presented by alleles within
      the B7 supertype. Substantial differences were observed in the ability of CTL to
      select for escape mutation when targeting the same epitope but restricted by
      different HLA. This observation was common to all six promiscuous B7 epitopes
      identified. Moreover, with one exception, there were no significant differences
      in the frequency, magnitude, or immunodominance of the CTL responses restricted
      by different HLA alleles to explain these discrepancies. This suggests that the
      unique peptide/MHC complexes generated by even closely related HLA induce CTL
      responses that are qualitatively different. This hypothesis is supported by
      additional differences observed between CTL targeting identical epitopes but
      restricted by different HLA: first, the occurrence of distinct, HLA-specific
      escape mutation; second, the recruitment of distinct TCR repertoires by
      particular peptide/MHC complexes; and, third, significant differences in the
      functional avidity of CTL. Taken together, these data indicate that significant
      functional differences exist between CTL targeting identical epitopes but
      restricted by different, albeit closely related HLA. These findings are of
      relevance to vaccine approaches that seek to exploit HLA supertypes to overcome
      the problem of HLA diversity.

PMID- 16982910
TI  - High vaccine efficacy against shigellosis of recombinant noninvasive Shigella
      mutant that expresses Yersinia invasin.
AB  - Live attenuated Shigella vaccines elicit protective immune responses, but involve
      a potential risk of inducing a strong inflammatory reaction. The bacterial
      invasiveness that is crucial for Ag delivery causes inflammatory destruction of
      infected epithelial cells and proinflammatory cell death of infected macrophages.
      In this study, the noninvasive Shigella mutant DeltaipaB was equipped with
      Yersinia invasin protein, which has been shown to mediate bacterial invasion and
      targeting to M cells located in follicle-associated epithelium. Invasin
      expressing DeltaipaB (DeltaipaB/inv) was internalized into epithelial cells and
      retained in the intraphagosomal space. DeltaipaB/inv did not induce necrotic cell
      death of infected macrophages nor cause symptomatic damage after intranasal
      vaccination of mice. DeltaipaB/inv was safer and more effective than the
      conventional live vaccine, DeltavirG. Infection by DeltaipaB/inv caused
      polymorphonuclear neutrophil infiltration in the lung, but did not induce
      production of large amounts of proinflammatory cytokines. We concluded that the
      low experimental morbidity and high vaccine efficacy of DeltaipaB/inv are
      primarily based on high protective immune responses, which may be enhanced by the
      polymorphonuclear neutrophil infiltration unaccompanied by tissue injury.

PMID- 16982911
TI  - Galectin-3 induces death of Candida species expressing specific beta-1,2-linked
      mannans.
AB  - Lectins play a critical role in host protection against infection. The galectin
      family of lectins recognizes saccharide ligands on a variety of microbial
      pathogens, including viruses, bacteria, and parasites. Galectin-3, a galectin
      expressed by macrophages, dendritic cells, and epithelial cells, binds bacterial
      and parasitic pathogens including Leishmania major, Trypanosoma cruzi, and
      Neisseria gonorrhoeae. However, there have been no reports of galectins having
      direct effects on microbial viability. We found that galectin-3 bound only to
      Candida albicans species that bear beta-1,2-linked oligomannans on the cell
      surface, but did not bind Saccharomyces cerevisiae that lacks beta-1,2-linked
      oligomannans. Surprisingly, binding directly induced death of Candida species
      containing specific beta-1,2-linked oligomannosides. Thus, galectin-3 can act as
      a pattern recognition receptor that recognizes a unique pathogen-specific
      oligosaccharide sequence. This is the first description of antimicrobial activity
      for a member of the galectin family of mammalian lectins; unlike other lectins of
      the innate immune system that promote opsonization and phagocytosis, galectin-3
      has direct fungicidal activity against opportunistic fungal pathogens.

PMID- 16982912
TI  - Activation of the lectin pathway by natural IgM in a model of
      ischemia/reperfusion injury.
AB  - Reperfusion of ischemic tissues elicits an acute inflammatory response involving
      serum complement, which is activated by circulating natural IgM specific to self
      Ags exposed by ischemia. Recent reports demonstrating a role for the lectin
      pathway raise a question regarding the initial events in complement activation.
      To dissect the individual roles of natural IgM and lectin in activation of
      complement, mice bearing genetic deficiency in early complement, IgM, or mannan
      binding lectin were characterized in a mesenteric model of ischemia reperfusion
      injury. The results reveal that IgM binds initially to ischemic Ag providing a
      binding site for mannan-binding lectin which subsequently leads to activation of
      complement and injury.

PMID- 16982913
TI  - TLR3 ligation activates an antiviral response in human fetal astrocytes: a role
      for viperin/cig5.
AB  - TLR3 functions as a viral nucleic acid sentinel activated by dsRNA viruses and
      virus replication intermediates within intracellular vesicles. To explore the
      spectrum of genes induced in human astrocytes by TLR3, we used a microarray
      approach and the analog polyriboinosinic polyribocytidylic acid (pIC) as ligand.
      As expected for TLR activation, pIC induced a wide array of cytokines and
      chemokines known for their role in inflammatory responses, as well as up
      regulation of the receptor itself. The data also showed activation of a broad
      spectrum of antiviral response genes. To determine whether pIC induced an
      antiviral state in astrocytes, a pseudotyped HIV viral particle, vesicular
      stomatitis virus g-env-HIV-1, was used. pIC significantly abrogated HIV-1
      replication, whereas IL-1, which also potently activates astrocytes, did not. One
      of the most highly up-regulated genes on microarray was the protein viperin/cig5.
      We found that viperin/cig5 expression was dependent on IFN regulatory factor 3
      and NF-kappaB signaling, and that repetitive stimulation with pIC, but not IL-1,
      further increased expression. Viperin induction could also be substantially
      inhibited by neutralizing Abs to IFN-beta, as could HIV-1 replication. To explore
      a role for viperin in IFN-beta-mediated inhibition of HIV-1, we used an RNA
      interference (RNAi) approach. RNAi directed against viperin, but not a scrambled
      RNAi, significantly inhibited viperin expression, and also significantly reversed
      pIC-induced inhibition of HIV-1 replication. We conclude that viperin contributes
      to the antiviral state induced by TLR3 ligation in astrocytes, supporting a role
      for astrocytes as part of the innate immune response against infection in the
      CNS.

PMID- 16982914
TI  - The monoclonal antibody CHO-131 identifies a subset of cutaneous lymphocyte
      associated antigen T cells enriched in P-selectin-binding cells.
AB  - T cells use the vascular adhesion molecules E- and P-selectin to enter inflamed
      skin. Previous studies have indicated the possibility for diversity in the
      synthesis of E- and P-selectin glycan ligands by activated T cells due to their
      different requirements for the O-glycan branching enzyme core 2 beta1,6-N
      acetylglucosaminyltransferase I and its independent regulation. It is known that
      T cell staining by the mAb HECA-452 (referred to as cutaneous lymphocyte
      associated Ag (CLA) T cells) correlates with E-selectin binding, yet whether
      these cells uniformly bind P-selectin is less clear. The mAb CHO-131 and P
      selectin binding require a glycan moiety consisting of a sialylated and
      fucosylated oligosaccharide properly positioned on a core-2 O-glycan.
      Interestingly, CHO-131 stains a subset of CLA(+) T cells. A direct comparison of
      the selectin binding capacity of CHO-131(+) and CHO-131(-) CLA(+) T cells
      revealed a significantly greater P-selectin, but not E-selectin, binding activity
      by the former subset. Based on the expression of homing and central and effector
      memory cell markers, CHO-131(+) and CHO-131(-) CLA(+) T cells have an overlapping
      skin-tropic and memory phenotype. CHO-131(+) T cells were considerably enriched
      in psoriatic skin, yet, unlike the peripheral blood of healthy individuals, HECA
      452 and CHO-131 stained a similar proportion of T cells in the cutaneous lesions,
      indicating an accumulation advantage by CHO-131(+) T cells. We conclude that the
      CHO-131(+)CLA(+) T cell subset is enriched in P-selectin binding cells. These
      findings should provide new insights into the regulation and function of skin
      homing T cells.

PMID- 16982915
TI  - Basal rather than induced heme oxygenase-1 levels are crucial in the antioxidant
      cytoprotection.
AB  - Heme oxygenase-1 (HO-1) overexpression protects against tissue injury in many
      inflammatory processes, including ischemia/reperfusion injury (IRI). This study
      evaluated whether genetically decreased HO-1 levels affected susceptibility to
      liver IRI. Partial warm ischemia was produced in hepatic lobes for 90 min
      followed by 6 h of reperfusion in heterozygous HO-1 knockout (HO-1(+/-)) and HO
      1(+/+) wild-type (WT) mice. HO-1(+/-) mice demonstrated reduced HO-1 mRNA/protein
      levels at baseline and postreperfusion. This corresponded with increased
      hepatocellular damage in HO-1(+/-) mice, compared with WT. HO-1(+/-) mice
      revealed enhanced neutrophil infiltration and proinflammatory cytokine (TNF
      alpha, IL-6, and IFN-gamma) induction, as well as an increase of intrahepatic
      apoptotic TUNEL(+) cells with enhanced expression of proapoptotic genes
      (Bax/cleaved caspase-3). We used cobalt protoporphyrin (CoPP) treatment to
      evaluate the effect of increased baseline HO-1 levels in both WT and HO-1(+/-)
      mice. CoPP treatment increased HO-1 expression in both animal groups, which
      correlated with a lower degree of hepatic damage. However, HO-1 mRNA/protein
      levels were still lower in HO-1(+/-) mice, which failed to achieve the degree of
      antioxidant hepatoprotection seen in CoPP-treated WT. Although the baseline and
      postreperfusion HO-1 levels correlated with the degree of protection, the HO-1
      fold induction correlated instead with the degree of damage. Thus, basal HO-1
      levels are more critical than the ability to up-regulate HO-1 in response to the
      IRI and may also predict the success of pharmacologically induced cytoprotection.
      This model provides an opportunity to further our understanding of HO-1 in stress
      defense mechanisms and design new regimens to prevent IRI.

PMID- 16982916
TI  - Follistatin-like protein-1 is a novel proinflammatory molecule.
AB  - While analyzing gene expression in collagen-induced arthritis, we discovered that
      a poorly characterized gene, follistatin-like protein 1 (FSTL-1), is highly
      overexpressed in mouse paws during early arthritis, especially at the interface
      of synovial pannus and eroding bone. In this study, we show that FSTL-1 is a
      novel proinflammatory molecule with a previously unrecognized role in
      inflammation. Transfection of FSTL-1 into macrophages and fibroblasts leads to up
      regulation of proinflammatory cytokines, including IL-1beta, TNF-alpha, and IL-6.
      Overexpression of FSTL-1 in mouse paws by gene transfer results in severe paw
      swelling and arthritis.

PMID- 16982917
TI  - TCR zeta down-regulation under chronic inflammation is mediated by myeloid
      suppressor cells differentially distributed between various lymphatic organs.
AB  - T cell AgR zeta chain down-regulation associated with T cell dysfunction has been
      described in cancer, infectious, and autoimmune diseases. We have previously
      shown that chronic inflammation is mandatory for the induction of an
      immunosuppressive environment leading to this phenomenon. To identify the key
      immunosuppressive components, we used an in vivo mouse model exhibiting chronic
      inflammation-induced immunosuppression. Herein, we demonstrate that: 1) under
      chronic inflammation secondary lymphatic organs display various immunological
      milieus; zeta chain down-regulation and T cell dysfunction are induced in the
      spleen, peripheral blood, and bone marrow, but not in lymph nodes, correlating
      with elevated levels of Gr1(+)Mac-1(+) myeloid suppressor cells (MSC); 2) MSC are
      responsible for the induction of such an immunosuppression under both normal and
      inflammatory conditions; and 3) normal T cells administered into mice exhibiting
      an immunosuppressive environment down-regulate their zeta expression. Such an
      environment is anticipated to limit the success of immunotherapeutic strategies
      based on vaccination and T cell transfer, which are currently under investigation
      for immunotherapy of cancer.

PMID- 16982918
TI  - Renal collecting duct epithelial cells react to pyelonephritis-associated
      Escherichia coli by activating distinct TLR4-dependent and -independent
      inflammatory pathways.
AB  - TLR4 plays a central role in resistance to pyelonephritis caused by uropathogenic
      Escherichia coli (UPEC). It has been suggested that renal tubule epithelial cells
      expressing TLRs may play a key role in inflammatory disorders and in initiating
      host defenses. In this study we used an experimental mouse model of ascending
      urinary tract infection to show that UPEC isolates preferentially adhered to the
      apical surface of medullary collecting duct (MCD) intercalated cells. UPEC
      infected C3H/HeJ (Lps(d)) mice carrying an inactivating mutation of tlr4 failed
      to clear renal bacteria and exhibited a dramatic slump in proinflammatory
      mediators as compared with infected wild-type C3H/HeOuJ (Lps(n)) mice. However,
      the level of expression of the leukocyte chemoattractants MIP-2 and TNF-alpha
      still remained greater in UPEC-infected than in naive C3H/HeJ (Lps(d)) mice.
      Using primary cultures of microdissected Lps(n) MCDs that expressed TLR4 and its
      accessory molecules MD2, MyD88, and CD14, we also show that UPECs stimulated both
      a TLR4-mediated, MyD88-dependent, TIR domain-containing adaptor-inducing IFN-beta
      independent pathway and a TLR4-independent pathway, leading to bipolarized
      secretion of MIP-2. Stimulation by UPECs of the TLR4-mediated pathway in Lps(n)
      MCDs leads to the activation of NF-kappaB, and MAPK p38, ERK1/2, and JNK. In
      addition, UPECs stimulated TLR4-independent signaling by activating a TNF
      receptor-associated factor 2-apoptosis signal-regulatory kinase 1-JNK pathway.
      These findings demonstrate that epithelial collecting duct cells are actively
      involved in the initiation of an immune response via several distinct signaling
      pathways and suggest that intercalated cells play an active role in the
      recognition of UPECs colonizing the kidneys.

PMID- 16982920
TI  - A novel C5a receptor-tissue factor cross-talk in neutrophils links innate
      immunity to coagulation pathways.
AB  - Neutrophils and complement are key sentinels of innate immunity and mediators of
      acute inflammation. Recent studies have suggested that inflammatory processes
      modulate thrombogenic pathways. To date, the potential cross-talk between innate
      immunity and thrombosis and the precise molecular pathway by which complement and
      neutrophils trigger the coagulation process have remained elusive. In this study,
      we demonstrate that antiphospholipid Ab-induced complement activation and
      downstream signaling via C5a receptors in neutrophils leads to the induction of
      tissue factor (TF), a key initiating component of the blood coagulation cascade.
      TF expression by neutrophils was associated with an enhanced procoagulant
      activity, as verified by a modified prothrombin time assay inhibited by anti-TF
      mAb. Inhibition studies using the complement inhibitor compstatin revealed that
      complement activation is triggered by antiphospholipid syndrome (APS) IgG and
      leads to the induction of a TF-dependent coagulant activity. Blockade studies
      using a selective C5a receptor antagonist and stimulation of neutrophils with
      recombinant human C5a demonstrated that C5a, and its receptor C5aR, mediate the
      expression of TF in neutrophils and thereby significantly enhance the
      procoagulant activity of neutrophils exposed to APS serum. These results identify
      a novel cross-talk between the complement and coagulation cascades that can
      potentially be exploited therapeutically in the treatment of APS and other
      complement-associated thrombotic diseases.

PMID- 16982919
TI  - Cyclooxygenase-1 overexpression decreases Basal airway responsiveness but not
      allergic inflammation.
AB  - Pharmacological inhibition or genetic disruption of cyclooxygenase (COX)-1 or COX
      2 exacerbates the inflammatory and functional responses of the lung to
      environmentally relevant stimuli. To further examine the contribution of COX
      derived eicosanoids to basal lung function and to allergic lung inflammation,
      transgenic (Tr) mice were generated in which overexpression of human COX-1 was
      targeted to airway epithelium. Although no differences in basal respiratory or
      lung mechanical parameters were observed, COX-1 Tr mice had increased
      bronchoalveolar lavage fluid PGE(2) content compared with wild-type littermates
      (23.0 +/- 3.6 vs 8.4 +/- 1.4 pg/ml; p < 0.05) and exhibited decreased airway
      responsiveness to inhaled methacholine. In an OVA-induced allergic airway
      inflammation model, comparable up-regulation of COX-2 protein was observed in the
      lungs of allergic wild-type and COX-1 Tr mice. Furthermore, no genotype
      differences were observed in allergic mice in total cell number, eosinophil
      content (70 vs 76% of total cells, respectively), and inflammatory cytokine
      content of bronchoalveolar lavage fluid, or in airway responsiveness to inhaled
      methacholine (p > 0.05). To eliminate the presumed confounding effects of COX-2
      up-regulation, COX-1 Tr mice were bred into a COX-2 null background. In these
      mice, the presence of the COX-1 transgene did not alter allergen-induced
      inflammation but significantly attenuated allergen-induced airway
      hyperresponsiveness, coincident with reduced airway leukotriene levels.
      Collectively, these data indicate that COX-1 overexpression attenuates airway
      responsiveness under basal conditions but does not influence allergic airway
      inflammation.

PMID- 16982921
TI  - Complement-dependent control of teratoma formation by embryonic stem cells.
AB  - The fetus has pluripotent stem cells that when transferred to mature individuals
      can generate tumors. However, for reasons yet unknown, tumors form rarely in the
      fetus and/or the mother during normal gestation. We questioned whether the
      complement system might protect against tumor formation by pluripotent stem
      cells. Murine embryonic stem cells were notably more susceptible than
      cardiomyocytes differentiated from those cells to lysis by complement in
      heterologous and homologous sera. Treatment of embryonic stem cells with
      heterologous serum averted tumor formation after residual cells were transplanted
      into mice. Confirming the importance of homologous complement in preventing
      formation of tumors, untreated embryonic stem cells formed tumors more quickly in
      C3-deficient than in wild-type mice. Susceptibility of embryonic stem cells to
      complement required an intact alternative pathway and was owed at least in part
      to a relative deficiency of sialic acid on cell surfaces compared with
      differentiated cells. Susceptibility to complement and resistance to tumors was
      inversely related to the number of cells transferred. These findings show that
      formation of tumors from embryonic stem cells is controlled in part by the
      alternative pathway of complement and suggest that susceptibility to complement
      might represent a general property of pluripotent stem cells that can be
      exploited to prevent tumor formation.

PMID- 16982923
TI  - Regulation of IL-1 and TNF receptor expression and function by endogenous
      macrophage migration inhibitory factor.
AB  - Macrophage migration inhibitory factor (MIF) has a key role in regulation of
      innate and adaptive immunity and is implicated in sepsis, tumorigenesis, and
      autoimmune disease. MIF deficiency or immunoneutralization leads to protection
      against fatal endotoxic, exotoxic, and infective shock, and anti-inflammatory
      effects in other experimental models of inflammatory disease. We report a novel
      regulatory role of MIF in type 1 IL-1R and p55 TNFR expression and function.
      Compared with wild-type cells, MIF-deficient cells were hyporesponsive to IL-1-
      and TNF-induced MAPK activity, AP-1 activity, and cellular proliferation, while
      NF-kappaB function was preserved. Hyporesponsiveness of MIF-deficient cells was
      associated with down-regulation of cytokine receptor expression, which was
      restored by reconstitution of either an upstream kinase of MAPK, MAPK/ERK kinase,
      or MIF. These data suggest that endogenous MIF is required for cytokine
      activation of MAPK/AP-1 and cytokine receptor expression. This autocrine
      regulatory pathway defines an important amplifying role of endogenous MIF in
      cytokine-mediated immune and inflammatory diseases and provides further molecular
      evidence for the critical role of MIF in cellular activation.

PMID- 16982922
TI  - A role for inflammatory mediators in the induction of immunoregulatory B cells.
AB  - UV exposure suppresses the immune response to a variety of microbial, fungal, and
      viral Ags. In addition, UV radiation is a complete carcinogen and the immune
      suppression induced by UV radiation is a major risk factor for skin cancer
      induction. In this study, we examined the mechanisms underlying the induction of
      immune suppression and tolerance induction by UV radiation. Transferring lymph
      nodes cells from UV-irradiated, FITC-sensitized mice into normal recipients
      transferred immune tolerance. Contrary to expectations, the cell responsible was
      an FITC(+), IL-10-secreting, CD19(+), B220(+) B cell. Because the lipid mediator
      of inflammation, platelet-activating factor (PAF) is released by UV-irradiated
      keratinocytes and is essential for the induction of immune suppression, we
      determined its role in tolerance induction. When UV-irradiated mice were injected
      with PCA 4248, a selective PAF receptor (PAFR) antagonist, transfer of tolerance
      was suppressed. However, immune suppression was not transferred when FITC(+)
      cells from the draining lymph nodes of UV-irradiated, PAFR-deficient donor mice
      were injected into the recipients. Because PCA 4248 also blocks serotonin
      receptor binding, we measured the effect that blocking both serotonin and PAFR
      binding has on the transfer of immune suppression. Only when both PAF and
      serotonin binding were blocked could we inhibit tolerance induction. These data
      identify a novel function for PAF and serotonin in modulating immune function,
      the activation of immunoregulatory B cells.

PMID- 16982924
TI  - A microbial TLR2 agonist imparts macrophage-activating ability to apolipoprotein
      A-1.
AB  - There is increasing epidemiologic evidence implying a role for chronic infection
      in atherosclerosis and that microbial TLR agonists may contribute to this
      disease. Mycoplasma arthritidis is an agent of acute and chronic inflammatory
      disease in rodents, and has been used extensively as a model for defining the
      mechanisms involved in arthritis and other inflammatory diseases. We have
      purified a 28-kDa, apolipoprotein A-1 (apoA-1)-like TLR2-dependent macrophage
      activating moiety from a culture of a virulent strain of M. arthritidis. ApoA-1
      similarly isolated from uninoculated mycoplasma medium was without bioactivity.
      The activity of the mycoplasma-derived molecule was resistant to heat and to
      digestion with proteinase K, but was susceptible to alkaline hydrolysis and
      H(2)O(2) oxidation. Infrared profiles of normal apoA-1 and that derived from
      mycoplasma were distinct. Unlike the activity of other mycoplasmal TLR2 agonists
      such as macrophage-activating lipopeptide-2, activity of the M. arthritidis
      derived 28-kDa component was dependent upon CD14, a coreceptor for LPS. Finally,
      we showed that bioactive lipopeptides prepared from M. arthritidis grown in serum
      free medium and also from a 41-kDa known bioactive lipoprotein of M. arthritidis,
      avidly bound to purified apoA-1 that separated out by SDS-PAGE, induced TNF-alpha
      and IL-12p40 both in vitro and in vivo. ApoA-1 is a key functional component of
      the high-density lipoprotein cholesterol complex by scavenging and removing
      unwanted lipids. Our finding that this molecule can acquire macrophage-activating
      properties from microbial TLR2-dependent agonists suggests a novel mechanism
      whereby some microbial agents might reverse the protective role of apoA-1, thus
      contributing to the genesis of atherosclerosis.

PMID- 16982925
TI  - Exposure of the promonocytic cell line THP-1 to Escherichia coli induces IFN
      gamma-inducible lysosomal thiol reductase expression by inflammatory cytokines.
AB  - IFN-gamma-inducible lysosomal thiol reductase (GILT), which plays a role in MHC
      class II-restricted processing and presentation of Ags containing disulfide
      bonds, can be induced in various cell types by the cytokine IFN-gamma. APCs,
      including circulating macrophages, constitutively express high levels of GILT,
      although the pathways regulating its expression in these cells have not been
      characterized. In this study, we used the promonocytic cell line THP-1, an
      established model for monocyte to macrophage differentiation, to investigate the
      induction of GILT upon exposure to bacteria. We show that contact with LPS or
      intact Escherichia coli causes THP-1 cells to undergo programmed differentiation,
      characterized by adhesion, cytokine secretion, and up-regulation of Ag processing
      and presentation components, including GILT. Unlike GILT induction in response to
      IFN-gamma treatment, induction by bacteria is dependent on new protein synthesis,
      NF-kappaB signaling, and secretion of the inflammatory cytokines TNF and IL
      1beta. Furthermore, we show that both cytokines are sufficient for GILT induction
      in the absence of a microbial stimulus. The majority of GILT synthesized by
      differentiated THP-1 cells is secreted as the precursor form rather than being
      transported to, and maturing in, lysosomes, suggesting a novel role for GILT in
      cells of the macrophage lineage.

PMID- 16982926
TI  - Collaborative action of NF-kappaB and p38 MAPK is involved in CpG DNA-induced IFN
      alpha and chemokine production in human plasmacytoid dendritic cells.
AB  - CpG DNA induces plasmacytoid dendritic cells (pDC) to produce type I IFN and
      chemokines. However, it has not been fully elucidated how the TLR9 signaling
      pathway is linked to these gene expressions. We examined the mechanisms involving
      the TLR9 and type I IFN signaling pathways, in relation to CpG DNA-induced IFN
      alpha, IFN regulatory factor (IRF)-7, and chemokines CXCL10 and CCL3 in human
      pDC. In pDC, NF-kappaB subunits p65 and p50 were constitutively activated. pDC
      also constitutively expressed IRF-7 and CCL3, and the gene expressions seemed to
      be regulated by NF-kappaB. CpG DNA enhanced the NF-kappaB p65/p50 activity, which
      collaborated with p38 MAPK to up-regulate the expressions of IRF-7, CXCL10, and
      CCL3 in a manner independent of type I IFN signaling. We then examined the
      pathway through which IFN-alpha is expressed. Type I IFN induced the expression
      of IRF-7, but not of IFN-alpha, in a NF-kappaB-independent way. CpG DNA enabled
      the type I IFN-treated pDC to express IFN-alpha in the presence of NF-kappaB/p38
      MAPK inhibitor, and chloroquine abrogated this effect. With CpG DNA, IRF-7, both
      constitutively and newly expressed, moved to the nuclei independently of NF
      kappaB/p38 MAPK. These findings suggest that, in CpG DNA-stimulated human pDC,
      the induction of IRF-7, CXCL10, and CCL3 is mediated by the NF-kappaB/p38 MAPK
      pathway, and that IRF-7 is activated upstream of the activation of NF-kappaB/p38
      MAPK in chloroquine-sensitive regulatory machinery, thereby leading to the
      expression of IFN-alpha.

PMID- 16982927
TI  - Caveolin-1 regulates NF-kappaB activation and lung inflammatory response to
      sepsis induced by lipopolysaccharide.
AB  - Caveolin-1, the principal structural and signaling protein of caveolae, is
      implicated in NO-mediated cell signaling events, but its precise role in
      inflammation is not well understood. Using caveolin-1-knockout (Cav-1(-/-)) mice,
      we addressed the role of caveolin-1 in the lung inflammatory response to sepsis
      induced by i.p. injection of LPS. LPS-challenged wild-type (WT) lungs exhibited
      significant increases in neutrophil sequestration (approximately 16-fold), lung
      microvascular permeability K(f,c) (approximately 5.7-fold), and edema formation
      (approximately 1.6-fold). Compared with WT, Cav-1(-/-) lungs showed marked
      attenuation of LPS-induced neutrophil sequestration (approximately 11-fold
      increase) and inhibition of microvascular barrier breakdown and edema formation.
      Prevention of lung injury in Cav-1(-/-) mice was associated with decreased
      mortality in response to LPS challenge. To address the basis of the reduced
      inflammation and injury in Cav-1(-/-) lungs, we examined the role of NO because
      its plasma concentration is known to be increased in Cav-1(-/-) mice. Cav-1(-/-)
      mouse lungs demonstrated a significant increase in endothelial NO synthase (eNOS)
      derived NO production relative to WT, which is consistent with the role of
      caveolin-1 as a negative regulator of eNOS activity. Cav-1(-/-) lungs
      concurrently showed suppression of NF-kappaB activity and decreased transcription
      of inducible NO synthase and ICAM-1. Coadministration of LPS with the NO synthase
      inhibitor nitro-L-arginine in Cav-1(-/-) mice prevented the suppression of NF
      kappaB activity and restored lung polymorphonuclear leukocyte sequestration in
      response to LPS challenge. Thus, caveolin-1, through its ability to regulate eNOS
      derived NO production, is a crucial determinant of NF-kappaB activation and the
      lung inflammatory response to LPS.

PMID- 16982928
TI  - Eosinophil-derived cationic proteins activate the synthesis of remodeling factors
      by airway epithelial cells.
AB  - Eosinophil cationic proteins influence several biological functions of the
      respiratory epithelium, yet their direct contribution to airway remodeling has
      not been established. We show that incubation of the human bronchial epithelial
      cell line, BEAS-2B, or primary cultured human bronchial epithelial cells, normal
      human bronchial epithelial cells, with subcytotoxic concentrations (0.1, 0.3, and
      1 microM) of major basic protein (MBP), or eosinophil peroxidase (EPO), augmented
      the transcripts of endothelin-1, TGF-alpha, TGF-beta1, platelet-derived growth
      factor (PDGF)-beta, epidermal growth factor receptor, metalloproteinase (MMP)-9,
      fibronectin, and tenascin. A down-regulation of MMP-1 gene expression was
      observed exclusively in BEAS-2B cells. Cationic protein-induced transcriptional
      effects were followed by the release of endothelin-1, PDGF-AB in the supernatants
      by ELISA, and by a down- and up-regulation, respectively, in the levels of MMP-1
      and MMP-9 in cell lysates, by Western blot. Cell stimulation with the synthetic
      polycation, poly-L-arginine, reproduced some but not all effects of MBP and EPO.
      Finally, simultaneous cell incubation with the polyanion molecules, poly-L
      glutamic acid or heparin, restored MMP-1 gene expression but incompletely
      inhibited MBP- and EPO-induced transcriptional effects as well as endothelin-1
      and PDGF-AB release, suggesting that cationic proteins act partially through
      their cationic charge. We conclude that eosinophil-derived cationic proteins are
      able to stimulate bronchial epithelium to synthesize factors that influence the
      number and behavior of structural cells and modify extracellular matrix
      composition and turnover.

PMID- 16982930
TI  - Native high-density lipoprotein augments monocyte responses to lipopolysaccharide
      (LPS) by suppressing the inhibitory activity of LPS-binding protein.
AB  - High-density lipoprotein (HDL) is an abundant plasma lipoprotein that is
      generally thought to be anti-inflammatory in both health and infectious disease.
      It binds and neutralizes the bioactivity of the potent bacterial lipids, LPS and
      lipoteichoic acid, that stimulate host innate immune responses. LPS-binding
      protein (LBP) plays an important role in augmenting leukocyte responses to LPS,
      whereas high concentrations of LBP, in the range of those found in plasma, can be
      inhibitory. We found that native HDL (nHDL) augmented human monocyte responses to
      LPS in the presence of inhibitory concentrations of LBP as measured by production
      of TNF and other cytokines. HDL did not stimulate cells in the absence of LPS,
      and it did not augment responses that were stimulated by IL-1beta or lipoteichoic
      acid. This activity of HDL was inhibited by trypsin treatment, suggesting that
      one or more protein constituents of HDL are required. In contrast to nHDL, low
      density lipoprotein, and reconstituted HDL did not possess this activity. The
      total lipoprotein fraction of normal plasma had activity that was similar to that
      of nHDL, whereas lipoproteins from septic patients with reduced HDL levels had a
      reduced ability to augment responses to LPS; this activity was restored by adding
      normal HDL to the patient lipoproteins. Our results demonstrate a novel
      proinflammatory activity of HDL that may help maintain sensitive host responses
      to LPS by suppressing the inhibitory activity of LBP. Our findings also raise the
      possibility that the decline of HDL during sepsis may help control the response
      to LPS.

PMID- 16982929
TI  - Novel approach to inhibit asthma-mediated lung inflammation using anti-CD147
      intervention.
AB  - Extracellular cyclophilins have been well described as chemotactic factors for
      various leukocyte subsets. This chemotactic capacity is dependent upon
      interaction of cyclophilins with the cell surface signaling receptor CD147.
      Elevated levels of extracellular cyclophilins have been documented in several
      inflammatory diseases. We propose that extracellular cyclophilins, via
      interaction with CD147, may contribute to the recruitment of leukocytes from the
      periphery into tissues during inflammatory responses. In this study, we examined
      whether extracellular cyclophilin-CD147 interactions might influence leukocyte
      recruitment in the inflammatory disease allergic asthma. Using a mouse model of
      asthmatic inflammation, we show that 1) extracellular cyclophilins are elevated
      in the airways of asthmatic mice; 2) mouse eosinophils and CD4+ T cells express
      CD147, which is up-regulated on CD4+ T cells upon activation; 3) cyclophilins
      induce CD147-dependent chemotaxis of activated CD4+ T cells in vitro; 4) in vivo
      treatment with anti-CD147 mAb significantly reduces (by up to 50%) the
      accumulation of eosinophils and effector/memory CD4+ T lymphocytes, as well as Ag
      specific Th2 cytokine secretion, in lung tissues; and 5) anti-CD147 treatment
      significantly reduces airway epithelial mucin production and bronchial
      hyperreactivity to methacholine challenge. These findings provide a novel
      mechanism whereby asthmatic lung inflammation may be reduced by targeting
      cyclophilin-CD147 interactions.

PMID- 16982931
TI  - Essential role for IL-10 in resistance to lipopolysaccharide-induced preterm
      labor in mice.
AB  - IL-10 is highly expressed in the uterus and placenta and is implicated in
      controlling inflammation-induced pathologies of pregnancy. To investigate the
      role of IL-10 in regulating preterm labor, the response of IL-10 null mutant mice
      to low-dose LPS in late gestation was evaluated. When IL-10 null mutant C57BL/6
      (IL-10(-/-)) and control (IL-10(+/+)) mice were administered LPS on day 17 of
      pregnancy, the dose of LPS required to elicit 50% preterm fetal loss was 10-fold
      lower in IL-10(-/-) mice than in IL-10(+/+) mice. Surviving fetuses in IL-10(-/-)
      mice exhibited fetal growth restriction at lower doses of LPS than IL-10(+/+)
      mice. Marked elevation of LPS-induced immunoactive TNF-alpha and IL-6 was evident
      in the serum, uterus, and placenta of IL-10(-/-) mice, and TNF-alpha and IL-6
      mRNA expression was elevated in the uterus and placenta, but not the fetus. Serum
      IL-1alpha, IFN-gamma, and IL-12p40 were increased and soluble TNFRII was
      diminished in the absence of IL-10, with these changes also reflected in the
      gestational tissues. Administration of rIL-10 to IL-10(-/-) mice attenuated
      proinflammatory cytokine synthesis and alleviated their increased susceptibility
      to preterm loss. Exogenous IL-10 also protected IL-10(+/+) mice from fetal loss.
      These data show that IL-10 modulates resistance to inflammatory stimuli by down
      regulating proinflammatory cytokines in the uterus and placenta. Abundance of
      endogenous IL-10 in gestational tissues is therefore identified as a critical
      determinant of resistance to preterm labor, and IL-10 may provide a useful
      therapeutic agent in this common condition.

PMID- 16982932
TI  - Functional reversion of antigen-specific CD8+ T cells from patients with Hodgkin
      lymphoma following in vitro stimulation with recombinant polyepitope.
AB  - Recent studies on Hodgkin's lymphoma (HL) have indicated that patients with
      active disease display functional impairment of Ag-specific CD8+ T cells due to
      expansion of regulatory T cells at sites of disease and in the peripheral blood.
      Adoptive cellular immunotherapy based on EBV-specific CD8+ T cells has been
      explored with limited success to date. It has been proposed that improved
      targeting of these CD8+ T cells toward viral Ags that are expressed in HL may
      enhance future therapeutic vaccine strategies. In this study, we have developed a
      novel replication-deficient adenoviral Ag presentation system that is designed to
      encode glycine alanine repeat-deleted EBV nuclear Ag 1 covalently linked to
      multiple CD8+ T cell epitopes from latent membrane proteins 1 and 2. A single
      stimulation of CD8+ T cells from healthy virus carriers, and patients with HL
      with this adenoviral construct in combination with IL-2, was sufficient to
      reverse the functional T cell impairment and restored both IFN-gamma production
      and cytolytic function. More importantly, these activated CD8+ T cells responded
      to tumor cells expressing membrane proteins and recognized novel EBNA1 epitopes.
      Flow cytometric analysis revealed that a large proportion of T cells expanded
      from patients with HL were CD62L(high) and CD27(high), and CCR7(low), consistent
      with early to mid effector T cells. These findings provide an important platform
      for translation of Ag-specific adoptive immunotherapy for the treatment of EBV
      associated malignancies such as HL and nasopharyngeal carcinoma.

PMID- 16982934
TI  - An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL
      12/IL-23 in psoriasis.
AB  - Psoriasis is characterized by activation of T cells with a type 1 cytokine
      profile. IL-12 and IL-23 produced by APCs are essential for inducing Th1 effector
      cells. Promising clinical results of administration of an Ab specific for the p40
      subunit of IL-12 and IL-23 (anti-IL-12p40) have been reported recently. This
      study evaluated histological changes and mRNA expression of relevant cytokines
      and chemokines in psoriatic skin lesions following a single administration of
      anti-IL-12p40, using immunohistochemistry and real-time RT-PCR. Expression levels
      of type 1 cytokine (IFN-gamma) and chemokines (IL-8, IFN-gamma-inducible protein
      10, and MCP-1) were significantly reduced at 2 wk posttreatment. The rapid
      decrease of these expression levels preceded clinical response and histologic
      changes. Interestingly, the level of an anti-inflammatory cytokine, IL-10, was
      also significantly reduced. Significant reductions in TNF-alpha levels and
      infiltrating T cells were observed in high responders (improvement in clinical
      score, > or =75% at 16 wk), but not in low responders. Of importance, the levels
      of APC cytokines, IL-12p40 and IL-23p19, were significantly decreased in both
      responder populations, with larger decreases in high responders. In addition,
      baseline levels of TNF-alpha significantly correlated with the clinical
      improvement at 16 wk, suggesting that these levels may predict therapeutic
      responsiveness to anti-IL-12p40. Thus, in a human Th1-mediated disease, blockade
      of APC cytokines by anti-IL-12p40 down-regulates expression of type 1 cytokines
      and chemokines that are downstream of IL-12/IL-23, and also IL-12/IL-23
      themselves, with a pattern indicative of coordinated deactivation of APCs and Th1
      cells.

PMID- 16982933
TI  - An unconventional antigen translated by a novel internal ribosome entry site
      elicits antitumor humoral immune reactions.
AB  - Self-tumor Ags that elicit antitumor immune responses in responses to IFN-alpha
      stimulation remain poorly defined. We screened a human testis cDNA library with
      sera from three polycythemia vera patients who responded to IFN-alpha and
      identified a novel Ag, MPD6. MPD6 belongs to the group of cryptic Ags without
      conventional genomic structure and is encoded by a cryptic open reading frame
      located in the 3'-untranslated region of myotrophin mRNA. MPD6 elicits IgG Ab
      responses in a subset of polycythemia vera patients, as well as patients with
      chronic myelogenous leukemia and prostate cancer, suggesting that it is broadly
      immunogenic. The expression of myotrophin-MPD6 transcripts was up-regulated in
      some tumor cells, but only slightly increased in K562 cells in response to IFN
      alpha treatment. By using bicistronic reporter constructs, we showed that the
      translation of MPD6 was mediated by a novel internal ribosome entry site (IRES)
      upstream of the MPD6 reading frame. Furthermore, the MPD6-IRES-mediated
      translation, but not myotrophin-MPD6 transcription, was significantly up
      regulated in response to IFN-alpha stimulation. These findings demonstrate that a
      novel IRES-mediated mechanism may be responsible for the translation of
      unconventional self-Ag MPD6 in responsive to IFN-alpha stimulation. The eliciting
      antitumor immune response against unconventional Ag MPD6 in patients with
      myeloproliferative diseases suggests MPD6 as a potential target of novel
      immunotherapy.

PMID- 16982935
TI  - ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal
      center Th cells.
AB  - ICOS is expressed on activated T cells and particularly on CXCR5+ follicular Th
      cells in germinal centers (GC). Its deletion leads to a profound deficiency in
      memory B cell formation and switched Ab response in humans. Here, we show that in
      ICOS-deficient patients the generation of GCs is severely disturbed, and the
      numbers of circulating CXCR5+CD45RO+ memory CD4 T cells are significantly
      reduced, indicating an essential role of ICOS in the differentiation of CXCR5+CD4
      T cells. The GC-specific CD57+CXCR5+ subpopulation is virtually absent. In ICOS-/
      mice, the decrease of circulating CXCR5+CD4 T cells reflects the reduction of
      CXCR5+ follicular Th cells in lymph nodes and spleen. Therefore, in concurrence
      with the absence of CXCR5+ T cells in the blood of CD40L-deficient patients,
      these data support the hypothesis that circulating CD57+CXCR5+ T cells are GC
      derived and thus may serve as a surrogate marker for the presence of functional
      GCs in humans.

PMID- 16982936
TI  - Influenza vaccination as secondary prevention for cardiovascular disease: a
      science advisory from the American Heart Association/American College of
      Cardiology.
AB  - Evidence from cohort studies and a randomized clinical trial indicates that
      annual vaccination against seasonal influenza prevents cardiovascular morbidity
      and all-cause mortality in patients with cardiovascular conditions. The American
      Heart Association and American College of Cardiology recommend influenza
      immunization with inactivated vaccine (administered intramuscularly) as part of
      comprehensive secondary prevention in persons with coronary and other
      atherosclerotic vascular disease (Class I, Level B). Immunization with live,
      attenuated vaccine (administered intranasally) is not currently recommended
      [corrected] for persons with cardiovascular conditions. It is important to note
      that influenza vaccination coverage levels overall and in this population remain
      well below national goals and are marked by disparities across different age and
      ethnic groups. One of the barriers to vaccination for patients with
      cardiovascular disease is that cardiology practices frequently do not stock and
      administer influenza vaccine. Healthcare providers who treat individuals with
      cardiovascular disease can help improve influenza vaccination coverage rates by
      providing and strongly recommending vaccination to their patients before and
      throughout the influenza season.

PMID- 16982937
TI  - Death, cardiac dysfunction, and arrhythmias are increased by calmodulin kinase II
      in calcineurin cardiomyopathy.
AB  - BACKGROUND: Activation of cellular Ca2+ signaling molecules appears to be a
      fundamental step in the progression of cardiomyopathy and arrhythmias. Myocardial
      overexpression of the constitutively active Ca2+-dependent phosphatase
      calcineurin (CAN) causes severe cardiomyopathy marked by left ventricular (LV)
      dysfunction, arrhythmias, and increased mortality rate, but CAN antagonist drugs
      primarily reduce hypertrophy without improving LV function or risk of death.
      METHODS AND RESULTS: We found that activity and expression of a second Ca2+
      activated signaling molecule, calmodulin kinase II (CaMKII), were increased in
      hearts from CAN transgenic mice and that CaMKII-inhibitory drugs improved LV
      function and suppressed arrhythmias. We devised a genetic approach to "clamp"
      CaMKII activity in CAN mice to control levels by interbreeding CAN transgenic
      mice with mice expressing a specific CaMKII inhibitor in cardiomyocytes. We
      developed transgenic control mice by interbreeding CAN transgenic mice with mice
      expressing an inactive version of the CaMKII-inhibitory peptide. CAN mice with
      CaMKII inhibition had reduced risk of death and increased LV and ventricular
      myocyte function and were less susceptible to arrhythmias. CaMKII inhibition did
      not reduce transgenic overexpression of CAN or expression of endogenous CaMKII
      protein or significantly reduce most measures of cardiac hypertrophy.
      CONCLUSIONS: CaMKII is a downstream signal in CAN cardiomyopathy, and increased
      CaMKII activity contributes to cardiac dysfunction, arrhythmia susceptibility,
      and longevity during CAN overexpression.

PMID- 16982938
TI  - Role of store-operated calcium channels and calcium sensitization in normoxic
      contraction of the ductus arteriosus.
AB  - BACKGROUND: At birth, the increase in oxygen causes contraction of the ductus
      arteriosus, thus diverting blood flow to the lungs. Although this contraction is
      modulated by substances such as endothelin and dilator prostaglandins, normoxic
      contraction is an intrinsic property of ductus smooth muscle. Normoxic inhibition
      of potassium channels causes membrane depolarization and calcium entry through L
      type calcium channels. However, the studies reported here show that after
      inhibition of this pathway there is still substantial normoxic contraction,
      indicating the involvement of additional mechanisms. METHODS AND RESULTS: Using
      ductus ring experiments, calcium imaging, reverse-transcription polymerase chain
      reaction, Western blot, and cellular electrophysiology, we find that this
      depolarization-independent contraction is caused by release of calcium from the
      IP3-sensitive store in the sarcoplasmic reticulum, by subsequent calcium entry
      through store-operated channels, and by increased calcium sensitization of actin
      myosin filaments, involving Rho-kinase. CONCLUSIONS: Much of the normoxic
      contraction of the ductus arteriosus at birth is related to calcium entry through
      store-operated channels, encoded by the transient receptor potential superfamily
      of genes, and to increased calcium sensitization. A clearer understanding of the
      mechanisms involved in normoxic contraction of the ductus will permit the
      development of better therapy to close the patent ductus arteriosus, which
      constitutes approximately 10% of all congenital heart disease and is especially
      common in premature infants.

PMID- 16982939
TI  - Blood lead below 0.48 micromol/L (10 microg/dL) and mortality among US adults.
AB  - BACKGROUND: Blood lead levels above 0.48 micromol/L (10 microg/dL) in adults have
      been associated with increased risk of cardiovascular, cancer, and all-cause
      mortality. The objective of the present study was to determine the association
      between blood lead levels below 0.48 micromol/L and mortality in the general US
      population. METHODS AND RESULTS: Blood lead levels were measured in a nationally
      representative sample of 13,946 adult participants of the Third National Health
      and Nutrition Examination Survey recruited in 1988 to 1994 and followed up for up
      to 12 years for all-cause and cause-specific mortality. The geometric mean blood
      lead level in study participants was 0.12 micromol/L (2.58 microg/dL). After
      multivariate adjustment, the hazard ratios (95% CI) for comparisons of
      participants in the highest tertile of blood lead (> or = 0.17 micromol/L [> or =
      3.62 microg/dL]) with those in the lowest tertile (< 0.09 micromol/L [< 1.94
      microg/dL]) were 1.25 (1.04 to 1.51; P(trend) across tertiles = 0.002) for all
      cause mortality and 1.55 (1.08 to 2.24; P(trend) across tertiles = 0.003) for
      cardiovascular mortality. Blood lead level was significantly associated with both
      myocardial infarction and stroke mortality, and the association was evident at
      levels > 0.10 micromol/L (> or = 2 microg/dL). There was no association between
      blood lead and cancer mortality in this range of exposure. CONCLUSIONS: The
      association between blood lead levels and increased all-cause and cardiovascular
      mortality was observed at substantially lower blood lead levels than previously
      reported. Despite the marked decrease in blood lead levels over the past 3
      decades, environmental lead exposures remain a significant determinant of
      cardiovascular mortality in the general population, constituting a major public
      health problem.

PMID- 16982940
TI  - Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors: results
      from the CRUSADE (Can Rapid risk stratification of Unstable angina patients
      Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines)
      initiative.
AB  - BACKGROUND: Glycoprotein (GP) IIb/IIIa inhibitors are beneficial in patients with
      non-ST-segment elevation acute coronary syndromes (NSTE ACS); their safe use in
      women, however, remains a concern. The contribution of dosing to the observed sex
      related differences in bleeding is unknown. METHODS AND RESULTS: We explored the
      relationship between patient sex, GP IIb/IIIa inhibitor use, dose, and bleeding
      in 32 601 patients with NSTE ACS across 400 CRUSADE (Can Rapid risk
      stratification of Unstable angina patients Suppress ADverse outcomes with Early
      implementation of the ACC/AHA guidelines) hospitals, of whom 18 436 were treated.
      GP IIb/IIIa inhibitor dose was defined as excessive if not reduced when
      creatinine clearance was < 50 mL/min for eptifibatide or < 30 mL/min for
      tirofiban. Major bleeding was defined as a hematocrit drop > or = 0.12, need for
      transfusion, or intracranial bleeding. Major bleeding was adjusted for clinical
      factors and antithrombotic dose. The risk for bleeding attributable to excess GP
      IIb/IIIa dose was determined by sex using prevalence and adjusted odds ratios
      (ORs). Women had higher rates of major bleeding than men among those treated with
      GP IIb/IIIa inhibitors (15.7% versus 7.3%, P<0.0001) and among those not treated
      (8.5% versus 5.4%, P<0.0001). Despite similar serum creatinine levels, creatinine
      clearance averaged 20 points lower among treated women than men. Treated women
      were also more likely to receive excess GP IIb/IIIa doses than men (46.4% versus
      17.2%, P<0.0001; adjusted OR 3.81, 95% confidence interval [CI] 3.39 to 4.27).
      Excess dosing was associated with increased risk of bleeding in women (OR 1.72,
      95% CI 1.30 to 2.28) and men (OR 1.27, 95% CI 0.97 to 1.66); however, bleeding
      risk attributable to dosing was much higher in women (25.0% versus 4.4%).
      CONCLUSIONS: Women experience more bleeding than men whether or not they are
      treated with GP IIb/IIIa inhibitors; however, because of frequent excessive
      dosing in women, up to one fourth of this sex-related risk difference in bleeding
      is avoidable. Appropriate dosing will improve care of all patients with NSTE ACS,
      with a particular benefit for women.

PMID- 16982941
TI  - Exercise and respiratory training improve exercise capacity and quality of life
      in patients with severe chronic pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH) is associated with restricted physical
      capacity, limited quality of life, and a poor prognosis because of right heart
      failure. The present study is the first prospective randomized study to evaluate
      the effects of exercise and respiratory training in patients with severe
      symptomatic PH. METHODS AND RESULTS: Thirty patients with PH (21 women; mean age,
      50+/-13 years; mean pulmonary artery pressure, 50+/-15 mm Hg; mean World Health
      Organization [WHO] class, 2.9+/-0.5; pulmonary arterial hypertension, n=23;
      chronic thromboembolic PH, n=7) on stable disease-targeted medication were
      randomly assigned to a control (n=15) and a primary training (n=15) group.
      Medication remained unchanged during the study period. Primary end points were
      the changes from baseline to week 15 in the distance walked in 6 minutes and in
      scores of the Short Form Health Survey quality-of-life questionnaire. Changes in
      WHO functional class, Borg scale, and parameters of echocardiography and gas
      exchange also were assessed. At week 15, patients in the primary and secondary
      training groups had an improved 6-minute walking distance; the mean difference
      between the control and the primary training group was 111 m (95% confidence
      interval, 65 to 139 m; P<0.001). Exercise training was well tolerated and
      improved scores of quality of life, WHO functional class, peak oxygen
      consumption, oxygen consumption at the anaerobic threshold, and achieved
      workload. Systolic pulmonary artery pressure values at rest did not change
      significantly after 15 weeks of exercise and respiratory training (from 61+/-18
      to 54+/-18 mm Hg) within the training group. CONCLUSIONS: This study indicates
      that respiratory and physical training could be a promising adjunct to medical
      treatment in severe PH. The effects add to the beneficial results of modern
      medical treatment.

PMID- 16982942
TI  - High-density lipoproteins and their constituent, sphingosine-1-phosphate,
      directly protect the heart against ischemia/reperfusion injury in vivo via the
      S1P3 lysophospholipid receptor.
AB  - BACKGROUND: All treatments of acute myocardial infarction are aimed at rapid
      revascularization of the occluded vessel; however, no clinical strategies are
      currently available to protect the heart from ischemia/reperfusion injury after
      restitution of blood flow. We hypothesized that some of the cholesterol transport
      independent biological properties of high-density lipoprotein (HDL) implied in
      atheroprotection may also be beneficial in settings of acute myocardial
      reperfusion injury. METHODS AND RESULTS: In an in vivo mouse model of myocardial
      ischemia/reperfusion, we observed that HDL and its sphingolipid component,
      sphingosine-1-phosphate (S1P), dramatically attenuated infarction size by
      approximately 20% and 40%, respectively. The underlying mechanism was an
      inhibition of inflammatory neutrophil recruitment and cardiomyocyte apoptosis in
      the infarcted area. In vitro, HDL and S1P potently suppressed leukocyte adhesion
      to activated endothelium under flow and protected rat neonatal cardiomyocytes
      against apoptosis. In vivo, HDL- and S1P-mediated cardioprotection was dependent
      on nitric oxide (NO) and the S1P3 lysophospholipid receptor, because it was
      abolished by pharmacological NO synthase inhibition and was completely absent in
      S1P3-deficient mice. CONCLUSIONS: Our data demonstrate that HDL and its
      constituent, S1P, acutely protect the heart against ischemia/reperfusion injury
      in vivo via an S1P3-mediated and NO-dependent pathway. A rapid therapeutic
      elevation of S1P-containing HDL plasma levels may be beneficial in patients at
      high risk of acute myocardial ischemia.

PMID- 16982944
TI  - Images in cardiovascular medicine. Angiographic computed tomography for imaging
      of underdeployed intracranial stent.

PMID- 16982943
TI  - Role of endothelin-1 in exposure to high altitude: Acute Mountain Sickness and
      Endothelin-1 (ACME-1) study.
AB  - BACKGROUND: The degree of pulmonary hypertension in healthy subjects exposed to
      acute hypobaric hypoxia at high altitude was found to be related to increased
      plasma endothelin (ET)-1. The aim of the present study was to investigate the
      effects of ET-1 antagonism on pulmonary hypertension, renal water, and sodium
      balance under acute and prolonged exposure to high-altitude-associated hypoxia.
      METHODS AND RESULTS: In a double-blind fashion, healthy volunteers were randomly
      assigned to receive bosentan (62.5 mg for 1 day and 125 mg for the following 2
      days; n=10) or placebo (n=10) at sea level and after rapid ascent to high
      altitude (4559 m). At sea level, bosentan did not induce any significant changes
      in hemodynamic or renal parameters. At altitude, bosentan induced a significant
      reduction of systolic pulmonary artery pressure (21+/-7 versus 31+/-7 mm Hg,
      P<0.03) and a mild increase in arterial oxygen saturation versus placebo after
      just 1 day of treatment. However, both urinary volume and free water clearance
      (H2OCl/glomerular filtration rate) were significantly reduced versus placebo
      after 2 days of ET-1 antagonism (1100+/-200 versus 1610+/-590 mL; -6.7+/-3.5
      versus -1.8+/-4.8 mL/min, P<0.05 versus placebo for both). Sodium clearance and
      segmental tubular function were not significantly affected by bosentan
      administration. CONCLUSIONS: The present results indicate that the early
      beneficial effect of ET-1 antagonism on pulmonary blood pressure is followed by
      an impairment in volume adaptation. These findings must be considered for the
      prevention and treatment of acute mountain sickness.

PMID- 16982945
TI  - Images in cardiovascular medicine. Coronary collaterals in full effect.

PMID- 16982946
TI  - Images in cardiovascular medicine. Cannulation of a persistent left superior vena
      cava: a clue given by ECG guidance.

PMID- 16982947
TI  - Letter by Romanens and Miserez regarding article, "Effect of intensive versus
      standard lipid-lowering treatment with atorvastatin on the progression of
      calcified coronary atherosclerosis over 12 months: a multicenter, randomized,
      double-blind trial".

PMID- 16982948
TI  - Viewpoint: The immune system and atherosclerosis.

PMID- 16982949
TI  - From theory to practice: optimizing the efficiency of an inefficient circulation.

PMID- 16982950
TI  - Percutaneous coronary intervention "dominates" coronary artery bypass graft
      surgery for high-risk patients: good news for patients, a challenge for
      healthcare planners.

PMID- 16982951
TI  - Food and Drug Administration perspective: Magnetic resonance imaging of pacemaker
      and implantable cardioverter-defibrillator patients.

PMID- 16982952
TI  - Is it appropriate to make statins available over the counter? Over-the-counter
      statins are worth considering in primary prevention of cardiovascular disease.

PMID- 16982953
TI  - Is it appropriate to make statins available over the counter? The argument
      against the appropriateness of over-the-counter statins.

PMID- 16982954
TI  - Insulin resistance and obesity in a mouse model of systemic lupus erythematosus.
AB  - Accumulating data indicate that metabolic syndrome is an inflammatory condition.
      Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with
      nephritis and cardiovascular disease. Evidence suggests that individuals with SLE
      are at risk for developing insulin resistance; however, this has not been
      directly examined. Using an established mouse strain with SLE (NZBWF1), we
      examined whether SLE is associated with increased body weight and fat deposition.
      Mean arterial pressure was significantly increased (140+/-4 versus 114+/-2 mm Hg;
      n > or = 5) in SLE mice by 36 weeks of age compared with control mice (NZW/LacJ).
      Body weight in SLE mice was higher at each age compared with controls by 12%,
      22%, and 34% (n > 30). Visceral adipose tissue weight was increased in SLE by
      44%, 74%, and 117% at 8, 20, and 36 weeks, respectively (n > or = 12). Plasma
      leptin was increased in SLE mice (8.6+/-1.0 versus 24.7+/-2.2 ng/mL; n = 5), and
      renal and adipose tissue exhibited macrophage infiltration. Fasted insulin was
      higher in SLE mice (0.6+/-0.1 versus 1.4+/-0.3 ng/mL; n > or = 10), but fasted
      glucose was not different (94+/-5 versus 80+/-9; n > or = 9). A glucose tolerance
      test caused a significantly greater and longer increase in blood glucose from
      mice with SLE compared with control mice. Food intake was not different between
      control and SLE mice. However, mice with SLE demonstrated lower levels of
      nighttime activity than controls. These data show that the NZBWF1 strain may be
      an important model to study the effects of obesity and insulin resistance on SLE
      associated hypertension.

PMID- 16982955
TI  - Extensive genetic analysis of 10 candidate genes for hypertension in Japanese.
AB  - The identification of genes that contribute to essential hypertension has been
      hampered because of a lack of statistical power and problems with multiple
      testing. In the present study, we performed association analyses between the 161
      single nucleotide polymorphisms of 10 candidate genes and hypertension in a
      Japanese population recruited from the Suita Study (n=3654). We found that 5
      polymorphisms in the 3 genes (SLC9A2, UMOD, and ELN) were associated with
      hypertension status, and 4 of these 5 polymorphisms were also associated with
      blood pressure values with a classical criterion of P<0.05. However, when a
      Bonferroni correction for multiple testing was applied, none of the polymorphisms
      were associated with blood pressure levels. We also performed association
      analyses between these 5 polymorphisms and intermediate phenotypes corresponding
      with the functions of candidate genes, including the renin/aldosterone profile,
      plasma uric acid levels, and pulse wave velocity. The ELN 3'-untranslated region
      (-/A) polymorphism was found to significantly affect pulse wave velocity, an
      indicator of arterial stiffness. Associations of the ELN 3'-untranslated region (
      /A) polymorphism with hypertension and pulse wave velocity were reconfirmed in
      another set of the study population. Thus, ELN seems to contribute to blood
      pressure regulation by affecting arterial stiffness in Japanese.

PMID- 16982956
TI  - Heme oxygenase-1 inhibition of Nox oxidase activation is a microvascular
      endothelial antioxidant effect of NO.

PMID- 16982957
TI  - NO modulates NADPH oxidase function via heme oxygenase-1 in human endothelial
      cells.
AB  - NO is known to induce expression of heme oxygenase-1, an antioxidant enzyme in
      blood vessels. We tested whether NO might modulate the endothelial NADPH oxidase
      function via heme oxygenase-1. In human microvascular endothelial cells, the NO
      donor DETA-NONOate (0.1 to 1 mmol/L) strongly induced expression of heme
      oxygenase-1 but not Cu/Zn superoxide dismutase. This was associated with a
      reduction of the superoxide-generating capacity of NADPH oxidase, an effect that
      depended on de novo gene transcription and heme oxygenase-1 activity. Activation
      of NADPH oxidase by tumor necrosis factor (TNF) alpha increased generation of
      reactive oxygen species. DETA-NONOate alone had little effect on TNF-stimulated
      reactive oxygen species, but it enhanced the TNF response when: (1) heme
      oxygenase-1 expression was blocked with specific small-interfering RNA; (2) heme
      oxygenase-1 activity was blocked by zinc-protoporphyrin; or (3) NADPH oxidase
      activity was blocked by diphenyleneiodonium. Moreover, the heme oxygenase-1 end
      product bilirubin directly inhibited fully functional NADPH oxidase and seemed to
      interrupt the assembly and activation of the oxidase. In conclusion, NO may
      modulate superoxide production by NADPH oxidase in human vascular endothelial
      cells, at least partly by inducing heme oxygenase-1. Our results indicate that
      suppression of NADPH oxidase-dependent reactive oxygen species formation may
      represent a novel mechanism underlying the cardiovascular protective actions of
      heme oxygenase-1 and bilirubin.

PMID- 16982958
TI  - Large increases in hypertension diagnosis and treatment in Canada after a
      healthcare professional education program.
AB  - This study was conducted to compare the self-reported prevalence and treatment of
      hypertension in adult Canadians before and subsequent to the implementation of
      the Canadian Hypertension Education Program in 1999. Data were obtained from 5
      cycles of the Canadian Health Surveys between 1994 and 2003 on respondents aged >
      or = 20 years. Piecewise linear regression was used to calculate the average
      annual increase in rates, before and after 1999. Between 1994 and 2003, the
      percentage of adult Canadians aware of being diagnosed with hypertension
      increased by 51% (from 12.37% to 18.74%; P<0.001), and the percentage prescribed
      antihypertensive drugs increased by 66% (from 9.57% to 15.86%; P<0.001). After
      1999, there was approximately a doubling of the annual rate of increase in the
      diagnosis of hypertension (from 0.52% of the population per year before 1999 to
      1.03% per year after 1999; P<0.001) and the percentage prescribed
      antihypertensive drugs (from 0.54% of the population per year before 1999 versus
      0.98% per year after 1999; P<0.001). The proportion of those aware of the
      diagnosis of hypertension but not being treated with drugs was reduced by half
      between 1994 and 2003 (from 31.47% untreated to 15.34% untreated; P<0.001). There
      was a greater increase in awareness of hypertension and use of antihypertensive
      drugs among men compared with women after 1999. The large increase in the
      diagnosis and treatment of hypertension in Canada between 1994 and 2003 is
      consistent with an overall beneficial effect of the Canadian Hypertension
      Education Program, including a reduced gender gap in hypertension care.

PMID- 16982959
TI  - Digesting the remodeled heart: role of lysosomal cysteine proteases in heart
      failure.

PMID- 16982960
TI  - Elastolytic cathepsin induction/activation system exists in myocardium and is
      upregulated in hypertensive heart failure.
AB  - Cathepsins are cysteine proteases that participate in various types of tissue
      remodeling. However, their expressions during myocardial remodeling have not been
      examined. In this study, we investigated their expressions in the left
      ventricular (LV) myocardium of rats and humans with hypertension-induced LV
      hypertrophy or heart failure (HF). Real-time PCR and immunoblot analysis revealed
      that the abundance of cathepsin S mRNA or protein in the LV tissues was greater
      in rats or humans with HF than in those with hypertrophy or in control subjects.
      Immunostaining showed that cathepsin S was localized predominantly to cardiac
      myocytes and coronary vascular smooth muscle cells, but also overlapped in part
      with macrophages. Elastic lamina fragmentations significantly increased in the LV
      intramyocardial coronary arteries of HF rats. The amount of elastolytic activity
      in the extract of the LV myocardium was markedly increased for HF rats compared
      with controls, and this activity was mostly because of cathepsin S. Although the
      amount of elastin mRNA was increased in the LV myocardium of HF rats, the area of
      interstitial elastin was not. The expression of interleukin 1beta was increased
      in the LV myocardium of HF rats, and this cytokine was found to increase the
      expression and activity of cathepsin S in cultured neonatal cardiomyocytes. These
      results suggest that cathepsin S participates in pathological LV remodeling
      associated with hypertension-induced HF. This protease is, thus, a potential
      target for therapeutics aimed at preventing or reversing cardiac remodeling.

PMID- 16982961
TI  - Predicting stroke using 4 ambulatory blood pressure monitoring-derived blood
      pressure indices: the Ohasama Study.
AB  - We investigated the association between stroke and blood pressure (BP) indices
      (systolic BP [SBP], diastolic BP [DBP], mean BP [MBP], and pulse pressure [PP])
      determined by ambulatory BP monitoring. The predictive power for stroke of these
      indices was compared in the general Japanese population. We obtained ambulatory
      BP data in 1271 subjects (40% men) aged > or = 40 (mean: 61) years. During a mean
      follow-up of 11 years, 113 strokes were observed. The multivariate adjusted
      relative hazard and likelihood ratio for a 1-SD increase for each BP index was
      determined by Cox proportional hazard regression. Comparison of the likelihood
      ratio between Cox models including 2 indices and those including 1 index
      indicated that PP was significantly less informative than other indices (P<0.01
      when adding MBP, SBP, or DBP to the PP model; P>0.09 when adding PP to the model
      including another index). However, after removing age from covariates, PP became
      more informative than DBP and MBP (P<0.0001 when adding PP to the MBP or DBP
      model, whereas SBP was more informative than PP even after removing age; P<0.05
      when adding SBP to the PP model). In conclusion, PP was the weakest predictor of
      stroke. Exclusion of age from covariates increased the predictive power of PP,
      suggesting that the stroke risk associated with PP reflected the risk of aging
      per se.

PMID- 16982962
TI  - Prehypertension revisited.

PMID- 16982963
TI  - Is there a new treatment for hypertensive disease in the horizon? Role of soluble
      guanylate cyclase.

PMID- 16982964
TI  - Soluble guanylate cyclase stimulation on cardiovascular remodeling in angiotensin
      II-induced hypertensive rats.
AB  - It is unknown whether long-term pharmacological stimulation of soluble guanylate
      cyclase (sGC), elevating intracellular cGMP levels, has a beneficial effect on
      hypertension. The purpose of this study is to investigate the effects of BAY41
      2272, an orally available sGC stimulator, on cardiovascular remodeling in
      hypertensive rats. Eight-week-old male Wistar rats with hypertension induced by
      angiotensin II infused subcutaneously at 250 ng/kg per minute were treated orally
      with a low ([L] 2 mg/kg per day) or high ([H] 10 mg/kg per day) dose of BAY41
      2272 for 14 days. BAY41-2272-H partially suppressed the rise in blood pressure
      and reduced the heart weight (4.20+/-0.34 versus 3.68+/-0.20 mg/g; P<0.01),
      whereas BAY41-2272-L had no effect. However, both doses decreased the angiotensin
      II-induced left ventricular accumulation of collagen in the perivascular area (L,
      -20%, P<0.05; H, -30%, P<0.01) and myocardial interstitium (L, -21%, P<0.05; H, 
      38%, P<0.01), reducing the number of activated fibroblasts surrounding coronary
      arteries (L, -74%; H, -79%; P<0.05). BAY41-2272 downregulated the angiotensin II
      induced left ventricular gene expression of type 1 collagen (L, -41%, P<0.05; H, 
      49%, P<0.01) and transforming growth factor-beta1 (L, -49%, P<0.05; H, -65%,
      P<0.01). cGMP levels were elevated by BAY41-2272 not only in the left ventricle,
      but also in cultured cardiac fibroblasts, resulting in reduced thymidine
      incorporation into the cells. Thus, stimulation of sGC by BAY41-2272 attenuates
      fibrosis of the left ventricle in rats with angiotensin II-induced hypertension
      partly in a pressure-independent manner, suggesting an important role for sGC
      generating cGMP in inhibiting cardiovascular remodeling.

PMID- 16982965
TI  - Angiotensin II type 2 receptor expression after vascular injury: differing
      effects of angiotensin-converting enzyme inhibition and angiotensin receptor
      blockade.
AB  - It has been suggested that the effects of angiotensin II type 1 receptor (AT1R)
      blockers are in part because of angiotensin II type 2 receptor (AT2R) signaling.
      Interactions between the AT2R and kinins modulate cardiovascular function.
      Because AT2R expression increases after vascular injury, we hypothesized that the
      effects on vascular remodeling of the AT1R blocker valsartan and the ACE
      inhibitor benazepril require AT2R signaling through the bradykinin 1 and 2
      receptors (B1R and B2R). To test this hypothesis, Brown Norway rats were assigned
      to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT2R inhibitor),
      valsartan+des-arg9-[Leu8]-bradykinin (B1R inhibitor), valsartan+HOE140 (B2R
      inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week
      of treatment, carotid balloon injury was performed. Two weeks later, carotids
      were harvested for morphometry and analysis of receptor expression by
      immunohistochemistry and Western blotting. Valsartan and benazepril significantly
      reduced the intima:media ratio compared with vehicle. Blockade of AT2R, B1R, or
      B2R in the presence of valsartan prevented the reduction seen with valsartan
      alone. B2R blockade inhibited the effect of benazepril. Injury increased AT1R,
      AT2R, B1R, and B2R expression. Treatment with valsartan but not benazepril
      significantly increased intima AT2R expression 2-fold compared with vehicle,
      which was not reversed by inhibition of AT2R, B1R, and B2R. Functionally,
      valsartan increased intimal cGMP levels compared with vehicle, and this increase
      was inhibited by blocking the AT2R, B1R, and B2R. Results suggest that AT2R
      expression and increased cGMP represent a molecular mechanism that differentiates
      AT1R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors
      like benazepril.

PMID- 16982966
TI  - Antihypertensive prescribing: do we have reason to celebrate?

PMID- 16982967
TI  - Changes in antihypertensive prescribing during US outpatient visits for
      uncomplicated hypertension between 1993 and 2004.
AB  - Monitoring national patterns of antihypertensive drug therapy is essential to
      assessing adherence to treatment guidelines and the impact of major scientific
      publications on physician prescribing. We analyzed data from 2 US National
      Ambulatory Care Surveys to examine trends between 1993 and 2004 in the
      prescription of antihypertensive drug classes for uncomplicated hypertension and
      the association between thiazide and beta-blocker prescribing and physician and
      patient characteristics. Diuretic prescriptions remained level through 2001 (39%;
      95% CI: 34% to 44%) but increased to 53% (48% to 58%) in 2003, largely because of
      a 72% increase in thiazide prescriptions in the first quarter of 2003 (50%; 95%
      CI: 40% to 59%). However, these increases did not sustain in 2004. Beta-blocker
      prescriptions increased modestly from 1993 (24%; 95% CI: 19% to 29%) to 2004
      (33%; 95% CI: 28% to 39%). Prescription of calcium channel blockers and
      angiotensin-converting enzyme inhibitors declined significantly following the
      sixth Joint National Committee report, but both subsequently rebounded to
      prereport levels. Prescription of angiotensin II receptor blockers increased
      continuously from 1% in 1995 to 23% by 2004. Polytherapy prescriptions,
      particularly those involving > or = 3 drug classes, became increasingly
      prevalent, accounting for 60% of antihypertensive drug visits by 2004.
      Prescriptions of thiazides and beta-blockers were both more likely in 1998-2004
      (versus 1993-1997). Blacks, women, and hospital outpatients were more likely to
      receive thiazides. Also, cardiologists were more likely to prescribe beta
      blockers. Evidence-based guidelines for antihypertensive drug therapy do impact
      physician prescribing, but the impact seems to be short lived. Future
      interventions are imperative for promoting long-term adherence to published
      guidelines.

PMID- 16982968
TI  - Experience with surgical management of cholesteatomas.
AB  - OBJECTIVE: To evaluate long-term results after at least 10 years of follow-up for
      a common method of ear surgery for managing cholesteatomas. METHODS: This
      retrospective study was performed by assessing the medical records of adult
      patients who underwent canal-wall-down mastoidectomy for management of
      cholesteatomas. RESULTS: From January 1, 1989, through December 31, 1995, 148
      patients underwent surgery for cholesteatoma. Of these, 72 (48%) were treated by
      using the canal-wall-down method. During follow-up (10-16 years), 5 (7%) patients
      underwent at least 1 revision operation. Ten years after primary surgery, 69
      (96%) of the ears were dry and 55 (76%) had intact tympanic membranes with fair
      hearing in 30 (42%). One patient who was deaf was seen in this group of 72
      patients. The recurrence rate was 7%, independent of the size of the
      cholesteatoma, mastoid status, or labyrinth or footplate erosion. The major
      predisposing factor for recurrence was retraction, especially in the posterior
      superior quadrant. CONCLUSION: Our results showed that the surgical technique
      could be improved by using endoscopes to lower the recurrence rate and improve
      hearing results.

PMID- 16982969
TI  - Effects of type 2 diabetes mellitus on cochlear structure in humans.
AB  - OBJECTIVE: To evaluate the effects of type 2 diabetes mellitus on cochlear
      elements in humans. DESIGN: Comparative study of the histopathologic
      characteristics of human temporal bones. SETTING: Otopathology laboratory in a
      tertiary academic medical center. PATIENTS: Temporal bones from 18 patients with
      type 2 diabetes mellitus were divided into 2 groups according to the method of
      management of diabetes: insulin in 11 patients (mean age, 51.9 years; age range,
      44-65 years) and oral hypoglycemic agents in 7 patients (mean age, 54.4 years;
      age range, 45-64 years). The diabetic groups and 26 age-matched controls (mean
      age, 52.9 years) were examined using light microscopy, and the cochlear changes
      were compared between groups. MAIN OUTCOME MEASURES: Morphometric measurements of
      vessel wall thickness in the basilar membrane and stria vascularis were made in
      all turns of the cochlea at the midmodiolar level. Area measurements of the stria
      vascularis were made in all turns of the cochlea at the midmodiolar level.
      Cochlear reconstructions and standard cytocochleograms were prepared using an oil
      immersion objective. The number of spiral ganglion cells was determined for each
      segment of the cochlea. Comparisons were made in each segment between diabetic
      and control groups. RESULTS: In the insulin group, walls of the vessels of the
      basilar membrane and stria vascularis in all turns were significantly thicker
      than those of controls. Walls of the vessels of the stria vascularis in the basal
      turn were also significantly thicker in the oral hypoglycemic group than in
      controls. Atrophy of the stria vascularis in most turns of the insulin group and
      the lower middle turn of the oral hypoglycemic group was significantly greater
      than in the controls. Loss of cochlear outer hair cells was significantly greater
      in the lower and upper basal turns in both diabetic groups. No significant
      difference was found in the number of spiral ganglion cells or inner hair cells
      between groups. CONCLUSION: This study demonstrates that cochlear microangiopathy
      and degeneration of the stria vascularis and cochlear outer hair cells are found
      in patients with type 2 diabetes mellitus.

PMID- 16982970
TI  - Clinical predictors for hearing loss in children with bacterial meningitis.
AB  - OBJECTIVES: To identify clinical risk factors that predict a higher incidence of
      hearing loss in children with bacterial meningitis, to determine the overall
      incidence of hearing loss in a large group of children proven by culture findings
      to have bacterial meningitis, and to compare clinical characteristics among
      patients with Streptococcus pneumoniae meningitis and Neisseria meningitidis
      meningitis. DESIGN: Retrospective review SETTING: Tertiary pediatric hospital.
      PATIENTS: A total of 171 children identified with bacterial meningitis who met
      inclusion criteria over a consecutive 10-year period. MAIN OUTCOME MEASURE:
      Presence of sensorineural hearing loss. RESULTS: Of 134 patients who underwent
      audiologic testing during their initial hospitalization, 41 (30.6%) were found to
      have at least a unilateral mild sensorineural hearing loss. The incidence of
      hearing loss was greater in patients with S pneumoniae meningitis than in
      patients with N meningitidis meningitis (35.9% and 23.9%, respectively). Length
      of hospitalization, development of seizures, elevated cerebrospinal fluid
      protein, and decreased cerebrospinal fluid glucose were significant predictors
      for hearing loss in children with bacterial meningitis. These factors were not
      found to be as strong a predictor for hearing loss in patients with N
      meningitidis meningitis. Stability of hearing was demonstrated with limited
      follow-up audiometry. CONCLUSIONS: Sensorineural hearing loss is a common sequela
      in children with bacterial meningitis. Identification of hearing loss in children
      with bacterial meningitis and early rehabilitation will lessen the long-term
      educational and social difficulties these children may experience.

PMID- 16982971
TI  - Interrater and intrarater reliability in the evaluation of velopharyngeal
      insufficiency within a single institution.
AB  - OBJECTIVE: To explore the interrater and intrarater reliability in nasoendoscopic
      assessment of velopharyngeal (VP) function using the standardized reporting
      method described by Golding-Kushner within a single institution. DESIGN:
      Prospective blinded study. SETTING: Academic, tertiary care, pediatric hospital.
      PARTICIPANTS: Six health care providers (2 pediatric otolaryngology faculty
      members, 2 pediatric otolaryngology fellows, and 2 speech pathologists)
      independently rated 50 videotaped nasoendoscopy segments twice. The segments on
      the videotape were obtained in a clinical setting. MAIN OUTCOME MEASURES: The
      Golding-Kushner rating system was used to rate VP function. Raters described VP
      closure quantitatively by rating palatal and lateral pharyngeal wall movement for
      each segment. They also qualitatively described characteristics of the VP gap,
      rated gap size as none, small, medium, or large, and estimated the percentage gap
      size relative to the resting position. Reliability coefficients were calculated
      for the data sets. RESULTS: Fairly good interrater and intrarater reliability was
      seen in the quantitative measures. Faculty otolaryngologists rated segments more
      similarly to each other than did pediatric otolaryngology fellows, but intrarater
      reliability was similar for both the experienced and less experienced
      otolaryngologists. Less consistency was seen in the ratings of the speech
      pathologists. Raters tended to rate with less consistency when describing
      qualitative characteristics of the VP gap than when making quantitative
      measurements. CONCLUSIONS: The Golding-Kushner scale is a reasonably reliable
      tool for reporting nasoendoscopic findings at our institution. However, these
      data also indicate that there exists room for improvement and that rater training
      may increase reliability.

PMID- 16982972
TI  - Young patients with oral squamous cell carcinoma: study of the involvement of
      GSTP1 and deregulation of the Fanconi anemia genes.
AB  - OBJECTIVE: To investigate whether oral squamous cell carcinomas (OSCCs) from
      young (</=40 years) and older (>/=60 years) patients have differential expression
      levels of GSTP1, FANCA, FANCC, FANCD2, and FANCG. DESIGN: Quantitative real-time
      reverse transcriptase-polymerase chain reaction and immunohistochemical analysis
      were used to assess gene and protein expression, respectively. SETTING: This
      study was performed in a research institute within a hospital setting. PATIENTS:
      Our study group consisted of 104 patients (42 young and 62 older). We collected
      RNA from 32 OSCC samples (10 young and 22 older patients) for gene expression
      analysis. Seventy-seven OSCC samples (37 from young and 40 from older patients)
      were used for protein expression analysis. Five patients were studied in both
      analyses. RESULTS: Lower expression of GSTP1 (P = .04) and FANCA (P = .01) was
      observed in the tumors of young compared with older patients. We also detected
      lower expression of GSTP1 in the tumors of young patients compared with their
      nondysplastic mucosa (P = .01). FANCA was underexpressed in nondysplastic mucosa
      of young compared with older patients (P = .01). GSTP1 protein showed negative or
      low expression in 41% (n = 15 of 37) of young vs 5% (n = 2 of 40) of older
      patient tumors (P = .001). FANCG protein expression was absent or low in 81% (n =
      30 of 37) of young compared with 36% (n = 15 of 40) of older patient tumors
      (P<.001). CONCLUSIONS: Differences in expression levels of GSTP1, FANCA, and
      FANCG in OSCC of young and older patients suggest that different mechanisms may
      be involved in tumor development through defective carcinogen metabolism and/or
      DNA repair capabilities. GSTP1 plays a key role in detoxification; therefore,
      underexpression of this gene in tumors of young patients may cause deficient
      detoxification that could lead to an increased susceptibility to the development
      of oral carcinoma.

PMID- 16982973
TI  - Intracranial complications of sinusitis in children and adolescents and their
      outcomes.
AB  - OBJECTIVE: To gain insight into patterns of presentation, imaging,
      microbiological aspects, therapy, disease course, and outcome of intracranial
      complications of sinusitis (ICS), which are challenging conditions with the
      potential to cause significant morbidity and mortality. We reviewed our
      experience with ICS in children and adolescents. DESIGN: Consecutive case series
      with a mean follow-up of 12 months. SETTING: Tertiary pediatric referral center.
      PATIENTS: Consecutive sample of 25 children and adolescents treated for 35
      intracranial complications (mean age, 13.2 years [range, 4-18 years]).
      INTERVENTIONS: Medical and surgical management. MAIN OUTCOME MEASURES: Survival
      and temporary and permanent neurologic sequelae. RESULTS: Most patients were
      adolescents (n = 19; 76%) and male (n = 19; 76%). Epidural abscess was most
      common (13 complications), followed by subdural empyema (n = 9), meningitis (n =
      6), encephalitis (n = 2), intracerebral abscess (n = 2), and dural sinus
      thrombophlebitis (n = 2). Abscesses were primarily located in the frontal or
      frontoparietal regions. Magnetic resonance imaging was extensively used and was
      superior to contrast computed tomography in diagnosis. All patients received
      intravenous antibiotics, 21 underwent endoscopic sinus surgery, and 13 underwent
      neurosurgical drainage. Only 1 death occurred from sepsis secondary to meningitis
      (mortality, 4%). Overall, neurologic outcome was excellent. Although 10 patients
      (40%) had neurologic deficits, most resolved within 2 months. Only 2 patients had
      permanent neurologic sequelae. Among ICS, epidural abscess appeared to be a
      distinct clinical entity. Epidural abscesses typically presented without specific
      neurologic symptoms or signs, were more often associated with orbital
      complications, and had outcomes considerably better than the other ICS.
      CONCLUSION: Intracranial complications of sinusitis are challenging, but
      prognosis can be favorable in children and adolescents by using aggressive
      medical and surgical management.

PMID- 16982974
TI  - Laser epiglottopexy for laryngomalacia: 10 years' experience in the west of
      Scotland.
AB  - OBJECTIVES: To determine the results of laser epiglottopexy and to compare them
      with other surgical techniques for severe laryngomalacia. DESIGN: A retrospective
      10-year case note review of laser epiglottopexy for severe laryngomalacia.
      SETTING: Royal Hospital for Sick Children, Glasgow, Scotland. PATIENTS: The study
      population comprised 52 male and 24 female children who underwent surgery for
      laryngomalacia between January 1, 1993, and December 31, 2002. In all children
      except 2, the indication for surgery was stridor associated with poor feeding and
      failure to thrive. The age at presentation ranged from 5 days to 32 months (mean,
      16 weeks). Three had neurological problems, in 3 a syndrome was diagnosed, and 2
      were described as dysmorphic and no syndrome was diagnosed; 5 had a cardiac
      abnormality. Complete follow-up data were available for 59 children (78%).
      Intervention Laser epiglottopexy. MAIN OUTCOME MEASURE: Resolution of stridor and
      growth velocity. RESULTS: Resolution of stridor was complete in 34 children, with
      mild residual stridor in 4 and persistent stridor but good weight gain in 5 (73%
      improved sufficiently with 1 procedure). Improvement was documented objectively
      by measuring growth velocity. Two children required a brief period of intubation
      postoperatively, and 4 had postoperative respiratory tract infections. Seven
      children (12%) required revision endoscopic laser surgery to control symptoms.
      There were no cases of supraglottic stenosis. One child died of cardiac
      abnormalities, and 8 (14%) required a tracheostomy, of whom 6 had neurological or
      syndromal abnormalities and 2 had associated tracheomalacia. CONCLUSIONS: We
      describe a technique of laser epiglottopexy for laryngomalacia and present
      objective evidence of its efficacy by means of growth velocity charts in a
      retrospective review of laryngomalacia surgery over a 10-year period. We believe
      this to be a safe method for treating a self-limiting condition. We have had
      comparable success to other surgical techniques without having the risks of
      permanent scarring to the supraglottis.

PMID- 16982975
TI  - Overexpression of hepatocyte growth factor and its receptor c-Met in nasal
      polyps.
AB  - OBJECTIVES: To investigate the expression and distribution of hepatocyte growth
      factor (HGF) and c-Met proteins in normal nasal mucosa and in nasal polyps and to
      evaluate the possible effects of HGF and c-Met on the development of nasal
      polyps. DESIGN: Prospective study. SETTING: Tertiary academic institution.
      PATIENTS: Normal inferior turbinate mucosa was obtained from 20 patients
      undergoing surgery for augmentation rhinoplasty. Nasal polyps were obtained from
      20 patients undergoing endoscopic sinus surgery for chronic polypoid sinusitis.
      INTERVENTIONS: Semiquantitative reverse-transcriptase polymerase chain reaction,
      immunohistochemistry, and Western blot analysis were performed. MAIN OUTCOME
      MEASURES: The expression and distribution of HGF and c-Met were analyzed.
      RESULTS: Using immunohistochemistry, moderate to high levels of HGF were mainly
      localized in submucosal glands of nasal polyps, while c-Met was detected in
      submucosal glands and in epithelial cells. In normal turbinate mucosa,
      immunopositive HGF was detected in submucosal glands, where faint staining was
      found, while c-Met was noted in epithelial cells and in submucosal glands.
      Semiquantitative reverse-transcriptase polymerase chain reaction and Western blot
      analysis showed that HGF expression was increased in nasal polyps compared with
      that in normal turbinate mucosa. The same result was observed for c-Met.
      CONCLUSION: Elevated c-Met expression in combination with expression of HGF in
      nasal polyps may enhance the proliferation of epithelial cells and submucosal
      glandular cells through the release of HGF, which activates c-Met receptors in
      nasal polyps.

PMID- 16982976
TI  - Changes in nasal resistance and quality of life after endoscopic microdebrider
      assisted inferior turbinoplasty in patients with perennial allergic rhinitis.
AB  - OBJECTIVE: To assess objective and subjective outcomes in patients with perennial
      allergic rhinitis who had undergone endoscopic microdebrider-assisted inferior
      turbinoplasty. DESIGN: Prospective study. SETTING: Tertiary referral center.
      PATIENTS: Fifty patients with perennial allergic rhinitis who had substantial
      mucosal hypertrophy of the inferior turbinates and who underwent endoscopic
      microdebrider-assisted inferior turbinoplasty with follow-up 1 year after
      surgery. INTERVENTION: A newly designed microdebrider blade incorporated with an
      elevator was used to perform this procedure in the clinical setting with the
      patient under local anesthesia and with 30 degrees endoscopic guidance. MAIN
      OUTCOME MEASURES: Both objective outcome evaluated by total nasal resistance at
      anterior rhinomanometry and subjective outcome assessed with the
      Rhinoconjunctivitis Quality of Life Questionnaire were analyzed before and 1 year
      after surgery. RESULTS: The median total nasal resistance in 50 patients
      decreased from 0.45 Pa/cm(3) per second preoperatively to 0.28 Pa/cm(3) per
      second 1 year postoperatively, a statistically significant difference (P<.001).
      Compared with preoperative scores, the postoperative scores of these patients
      significantly improved in both 7 separate domain scores and overall
      Rhinoconjunctivitis Quality of Life Questionnaire scores (P<.005). CONCLUSION:
      Our results suggest that endoscopic microdebrider-assisted inferior turbinoplasty
      is effective for decreasing nasal resistance and improving quality of life in
      patients with perennial allergic rhinitis who have substantial nasal congestion.

PMID- 16982977
TI  - Effect of acid and pepsin on glottic wound healing: a simulated reflux model.
AB  - OBJECTIVE: To evaluate the effects of acid and pepsin on the healing of
      traumatized vocal folds in a simulated reflux model. Gastroesophageal reflux is
      related to various laryngeal manifestations. However, there is a lack of
      established reflux animal models that would ensure longer observation periods.
      DESIGN: A prospective randomized animal study. INTERVENTIONS: Forty-two rabbits
      underwent a stripping procedure of the unilateral glottis and catheter insertion
      under transoral endoscopic guidance. The animals were randomly assigned to a
      control group (n = 21; isotonic sodium chloride was used) or a reflux group (n =
      21, acid and pepsin were used). They received intrapharyngeal catheter irrigation
      with 3 mL of isotonic sodium chloride or a solution of acid with a pH of 3 and
      pepsin, 0.3 mg/mL, twice daily for 4 or 8 weeks after surgery. MAIN OUTCOME
      MEASURES: Gross and histologic findings of the preinjured glottides of the 2
      groups were compared. RESULTS: The catheter extrusion rate was significantly low
      (6%), and any catheter problems were immediately solved by reinsertion or
      reconnection. The extent of glottic scarring and frequency of granulation
      formation were higher in the reflux group compared with the control group
      (P<.05). Histologic inflammation scores and collagen deposition were
      significantly greater in the reflux group compared with the control group
      (P<.05). CONCLUSIONS: Our data suggest that glottic wound healing is
      significantly affected by acid and pepsin. Antireflux treatment can be advocated
      to minimize further injury caused by gastroesophageal reflux in patients who
      undergo laryngeal surgery.

PMID- 16982978
TI  - Differential expression of surfactant protein A in the nasal mucosa of patients
      with allergy symptoms.
AB  - OBJECTIVE: To characterize surfactant protein A (SP-A) expression in human nasal
      tissue and correlate differential expression of SP-A with symptoms suggestive of
      allergic rhinitis. DESIGN: Allergic rhinitis symptom data were prospectively
      collected in the form of the Rhinitis Symptom Utility Index, the
      Rhinoconjunctivitis Quality of Life Questionnaire, and a Visual Analog Scale.
      Immunohistochemical staining for SP-A was performed on resected nasal tissue.
      Quantitative polymerase chain reaction amplification of the SP-A gene referenced
      to beta-actin was performed on complementary DNA samples synthesized from total
      RNA isolates. SETTING: Academic tertiary referral center, department of
      otolaryngology laboratories. PATIENTS: Twenty-five consecutive patients
      undergoing nasal surgery. MAIN OUTCOME MEASURES: Immunohistochemical staining of
      SP-A in human nasal mucosa and submucosa, polymerase chain reaction amplification
      of SP-A messenger RNA, and rhinitis symptom scores. RESULTS: Immunostaining
      localized SP-A to the mucosa and submucosal glands in specimens. Quantitative
      polymerase chain reaction demonstrated correlation between SP-A messenger RNA
      concentration and the total Rhinitis Symptom Utility Index score (0.51, P = .009)
      as well as "sneezing over the previous week" (0.40, P = .049), "runny nose over
      the previous week" (0.55, P = .005), and "sneezing today" (0.47, P = .02).
      CONCLUSIONS: To our knowledge, this is the first report of SP-A expression in
      human nasal tissue. Furthermore, the degree of expression correlated with
      severity of disease as measured by the Rhinitis Symptom Utility Index in patients
      with allergic rhinitis symptoms.

PMID- 16982979
TI  - Antenatal carbimazole and choanal atresia: a new embryopathy.
AB  - Carbimazole embryopathy is a recently recognized and defined phenotype. Choanal
      atresia; gastrointestinal anomalies, particularly esophageal atresia; athelia or
      hypothelia; developmental delay; hearing loss; aplasia cutis; and dysmorphic
      facial features all can occur after exposure to the antithyroid drugs carbimazole
      or methimazole during gestation. Although full expression of this phenotype
      appears to be an uncommon sequelae of antenatal carbimazole exposure, infants
      with less overt manifestations may remain with the condition undiagnosed. It is
      clearly important when an infant with choanal atresia is assessed to take an
      adequate drug history and consider this embryopathy as a potential causative
      factor.

PMID- 16982980
TI  - Pathology quiz case 1. Metastatic mesothelioma involving the tongue.

PMID- 16982981
TI  - Pathology quiz case 2. Subglottic amyloidosis.

PMID- 16982983
TI  - Alar expansion and reinforcement: a new technique to manage nasal valve collapse.
AB  - OBJECTIVE: To describe the new technique of alar expansion and reinforcement as a
      comprehensive approach to the surgical management of nasal valve collapse.
      METHODS: Alar expansion and reinforcement expands the narrow nasal valve and
      reinforces the floppy nasal sidewall. Forty-one patients underwent rhinoplastic
      surgery for nasal valve collapse between May 1, 2002, and April 30, 2005, using
      an external rhinoplasty approach; of these, 32 responded to our postoperative
      questionnaire. Twenty-four patients (75%) underwent primary surgery and 8 (25%)
      had undergone previous rhinoplasty. All patients had permanent adjustable
      expansion sutures. Twelve patients (38%) had an excessively floppy nasal sidewall
      that required a high-density porous polyethylene alar batten implant to anchor
      the expansion sutures. Patients underwent clinical review from 6 months to 3
      years after surgery, and a telephone survey was used to evaluate their functional
      and cosmetic satisfaction rates. RESULTS: Thirty patients (94%) experienced good
      improvement in their nasal airway. The improvement in nasal airway patency was
      statistically significant (P<.001). Two patients (6%) reported no improvement.
      There were no complications. Cosmetic outcome was satisfactory in all 8 patients
      who also requested cosmetic improvement. Of the 24 patients who had surgery for
      nasal obstruction only, 10 (42%) rated their cosmetic appearance as better, with
      the remaining 14 (58%) indicating that they did not identify any significant
      change in their nasal appearance. CONCLUSION: Alar expansion and reinforcement is
      a safe, reliable, and effective technique to manage nasal valve collapse.

PMID- 16982984
TI  - The evolution of midface rejuvenation: combining the midface-lift and fat
      transfer.
AB  - OBJECTIVE: To evaluate the aesthetic results in our initial group of patients
      treated with a combination of a midface-lift and fat transfer compared with a
      randomly selected group of patients who underwent a midface-lift without
      concurrent fat transfer by one of us. METHODS: The setting was a private,
      ambulatory, surgical center. The design was a comparative study between patients
      who did or did not receive fat transfer in addition to a midface-lift to
      determine if the addition of fat transfer to the midface-lift resulted in an
      improved aesthetic outcome. A total of 40 patients with complete photographic and
      medical records and a minimum of 6 months of follow-up were included in the
      study. Group 1 consisted of 30 patients randomly selected (from >650 potential
      patients) who underwent a midface-lift without fat transfer to serve as a control
      group. Group 2 consisted of our initial 10 patients who underwent fat transfer in
      addition to a midface-lift at the same setting. The degree of aesthetic
      improvement in 4 facial zones was assessed by 3 independent blinded evaluators.
      Zone 1 represents the tear trough/infraorbital rim; zone 2, the malar eminence;
      zone 3, the submalar region; and zone 4, the nasolabial crease. Each zone was
      given a rating from 0 to 2 (0 for no improvement; 1, mild improvement; and 2,
      marked improvement). The 2 groups were compared with 4 chi(2) tests of
      independence. RESULTS: Four chi(2) tests of independence were conducted to
      compare the findings between group 1 and group 2. One hundred twenty ratings were
      conducted; group 1 consisted of 90 total ratings on 30 patients and group 2
      consisted of 30 total ratings on 10 patients. The first chi(2) (tear
      trough/infraorbital rim) test revealed a significant difference on tear trough
      ratings by group (chi(2)(2) = 73.59, P<.01). The second chi(2) test (malar
      eminence) did not reveal a significant difference on malar eminence ratings by
      group (chi(2)(2) = 3.10, P = .21). The third chi(2) test (submalar region) failed
      to reveal a significant difference on submalar region by group (chi(2)(2) = 4.01,
      P = .13). The final chi(2) test (nasolabial crease) revealed a significant
      difference on nasolabial ratings by group (chi(2)(2) = 14.28, P<.01).
      CONCLUSIONS: Our findings revealed a statistically significant difference between
      group 1 (no fat transfer) and group 2 (fat transfer) in the tear trough region
      (P<.01) and the nasolabial crease (P<.01). The fat transfer technique in
      combination with a midface-lift is a safe and effective means to provide more
      complete facial rejuvenation, especially in the regions of the tear trough and
      nasolabial crease.

PMID- 16982985
TI  - Analysis of outcomes after functional rhinoplasty using a disease-specific
      quality-of-life instrument.
AB  - OBJECTIVE: To measure the efficacy of functional rhinoplasty techniques with a
      validated quality-of-life instrument. DESIGN: Prospective observational outcomes
      study of patients with severe nasal obstruction owing to septal deviation,
      internal or external valve collapse, and turbinate hypertrophy who subsequently
      underwent functional rhinoplasty. Preoperative and postoperative evaluations were
      performed using the Nasal Obstruction Symptoms Evaluation scale. RESULTS: Forty
      one patients completed preoperative and postoperative evaluations. No
      complications occurred. There was a significant improvement in mean Nasal
      Obstruction Symptoms Evaluation score postoperatively for the entire cohort
      (P<.01). Nasal Obstruction Symptoms Evaluation scores were also examined based on
      the procedure performed, such as spreader grafting, septoplasty, external valve
      suspension, and turbinectomy. Each subgroup also demonstrated airway improvement.
      CONCLUSIONS: Functional rhinoplasty techniques are effective in improving nasal
      airway function as measured by a patient-based, disease-specific, quality-of-life
      instrument. The specific techniques considered to treat nasal obstruction can be
      tailored to address the areas of concern, including septal deviation, internal or
      external valve collapse, and turbinate hypertrophy.

PMID- 16982986
TI  - Use of hyperbaric oxygen to enhance auricular composite graft survival in the
      rabbit model.
AB  - OBJECTIVE: To evaluate the efficacy of using hyperbaric oxygen to enhance
      auricular composite graft survival via a prospective, randomized, placebo
      controlled, double-blind study. DESIGN: Eighteen New Zealand White rabbits were
      randomly assigned to treatment (n = 9) and control (n = 9) groups after
      amputation and reattachment of 20 x 10-mm auricular composite grafts. The
      treatment group received twice-daily hyperbaric oxygen treatments for 5 days. The
      control group received twice-daily hyperbaric room-air treatments for 5 days.
      After 21 days, digital photographs of the composite grafts were taken and
      compared with photographs taken on the day of surgery. From these photographs,
      digital imaging software was used to calculate the percentage of graft survival.
      RESULTS: The treated group (18 ears) had a mean +/- SD graft survival area of
      80.67% +/- 19%, whereas the control group (18 ears) had a mean +/- SD graft
      survival area of 26.33% +/- 29%. Variance analysis with the Snedecor test allowed
      the comparison of the groups. The paired, 2-tailed t test proved a significant
      difference (P<.001) between groups. CONCLUSION: Hyperbaric oxygen therapy is an
      effective way to enhance the survival of 2-cm auricular composite grafts.

PMID- 16982987
TI  - Validation of a quality-of-life instrument for patients with nonmelanoma skin
      cancer.
AB  - OBJECTIVE: To validate a disease-specific quality-of-life instrument--the Skin
      Cancer Index--intended to measure quality-of-life issues relevant to patients
      with nonmelanoma skin cancer. METHODS: Internal reliability, convergent and
      divergent validity with existing scales, and factor analyses were performed in a
      cross-sectional study of 211 patients presenting with cervicofacial nonmelanoma
      skin cancer to a dermatologic surgery clinic. RESULTS: Factor analyses of the
      Skin Cancer Index confirmed a multidimensional scale with 3 distinct subscales
      emotional, social, and appearance. Excellent internal validity of the 3 subscales
      was demonstrated. Substantial evidence was observed for convergent validity with
      the Dermatology Life Quality Index, Rosenberg Self-Esteem Scale, Lerman's Cancer
      Worry Scale, and Medical Outcomes Survey Short-Form 12 domains for vitality,
      emotion, social function, and mental health. CONCLUSIONS: These findings validate
      a new disease-specific quality-of-life instrument for patients with cervicofacial
      nonmelanoma skin cancer. Studies on the responsiveness of the Skin Cancer Index
      to clinical intervention are currently under way.

PMID- 16982988
TI  - The Korean American woman's nose: an in-depth nasal photogrammatic analysis.
AB  - OBJECTIVES: To assess the differences in nasal anthropometric measurements
      between Korean American women and North American white women and to perform an in
      depth nasal index calculation. METHODS: This anthropometric survey included a
      volunteer sample of Korean American women (n = 72) aged 18 to 35 years with
      Korean parents and no previous nasal surgery or trauma to the nose. Standardized
      and referenced frontal, lateral, and basal photographs of the nose were taken of
      the subjects and 22 standard anthropometric measurements of the nose were
      determined. Results were compared with published standards for North American
      white women. In addition, 18 nasal indices were calculated and compared with the
      published standards for North American white women. RESULTS: The Korean American
      woman's nose did not fit the neoclassic facial canons. Compared with North
      American white women, 20 of 22 nasal measurements in Korean American women were
      found to be significantly different. Nasal indices also revealed significant
      differences in 16 of the 18 that were calculated. The Korean American woman's
      nose exhibits less rotation, has a flatter dorsum, and is more flared at the
      alae, with less definition of the nasal tip. CONCLUSIONS: The average Korean
      American and North American white female nasal anthropometric measurements are
      very different. As cosmetic surgery becomes more popular among Asian Americans,
      our findings bolster the need for a broader view of facial analysis and
      transcultural aesthetics.

PMID- 16982989
TI  - The lip-cheek groove: a new analysis with treatment options.
AB  - OBJECTIVE: To present a clinical classification of the lip-cheek groove. DESIGN:
      The clinical classification, which is based on years of analysis, will provide
      optimal management options for achieving the greatest degree of correction and
      rejuvenation of the lip-cheek groove. RESULTS: The use of the clinical
      classification of the lip-cheek groove will guide the surgeon to the management
      option(s) that will attain the best aesthetic outcome. CONCLUSION: The
      classification of the lip-cheek groove enables the surgeon to choose the optimal
      approach for improvement of the groove.

PMID- 16982990
TI  - Effects of tamoxifen on normal human dermal fibroblasts.
AB  - OBJECTIVE: To evaluate the effects of tamoxifen on the growth and autocrine
      growth factor production of human dermal fibroblasts from the face. METHODS: In
      vitro study of normal adult dermal fibroblast cells developed from surgical
      specimens in a serum-free model. Cell cultures were exposed to 5-, 8-, 12-, 16-,
      and 50-microg/mL concentrations of tamoxifen solution. Cell counts were
      performed, and the cell-free supernatants were collected at 0, 1, 3, 5, and 7
      days after the initial exposure. Population doubling times were calculated, and
      supernatants were quantitatively assayed for basic fibroblast growth factor
      (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor
      (TGF) beta1. RESULTS: Tamoxifen appears to delay cellular proliferation rates in
      a dose-dependent manner up to a concentration of 12 microg/mL. Higher
      concentrations, approaching 50 microg/mL, appear to have a toxic effect on cell
      growth. The analysis of growth factor production revealed decreased levels of
      bFGF and VEGF but no change in the levels of TGF-beta1. CONCLUSIONS: The in vitro
      findings of delayed cell proliferation and decreased production of VEGF and bFGF
      in cells exposed to tamoxifen are consistent with previous in vivo reports of
      delayed wound healing but improved scar formation. The in vitro findings of
      growth factor modulation by tamoxifen provide cellular and molecular evidence
      supporting the clinical use of tamoxifen to ultimately improve scar formation.

PMID- 16982991
TI  - Lateral crus pull-up: a method for collapse of the external nasal valve.
AB  - Collapse of the nasal vestibule during inspiration is a frequently encountered
      symptom, often caused by weak or medially displaced lateral crura in the lower
      lateral cartilages. Numerous techniques are available for lateralizing and
      strengthening the lateral crura using cartilage grafts or suture techniques. In
      most cases, they involve an external rhinoplasty approach or additional
      incisions. An elegant endonasal method for widening and strengthening the lateral
      component of the nasal valve area is described herein. The basis of the procedure
      is a permanent submucosal spanning suture between the piriform aperture and the
      distal part of the lower lateral cartilage. The effect of this technique is 2
      fold. First, it provides superolateral rotation of the lateral crura, increasing
      the cross-sectional area, and second, the spanning suture provides additional
      support for the lateral wall of the nasal vestibule.

PMID- 16982992
TI  - Medical licensure and the Federation of State Medical Boards.

PMID- 16982993
TI  - Rhinoplasty techniques: a historical perspective and survey of 8155 single
      surgeon cases.

PMID- 16982995
TI  - Mapping pain generators for surgical treatment of migraine headaches.

PMID- 16982994
TI  - Senescence, a multifactorial problem.

PMID- 16982996
TI  - Bartolome Esteban Murillo's Saint Justa.

PMID- 16982997
TI  - The cutting edge. Severe hidradenitis suppurativa treated with adalimumab.

PMID- 16982998
TI  - Identification of clinically featureless incipient melanoma using sequential
      dermoscopy imaging.
AB  - OBJECTIVES: To examine the role of sequential dermoscopy imaging in detecting
      incipient melanoma and to elucidate the impact of length of follow-up on the
      relevance of observed changes. DESIGN: Baseline and follow-up images of melanomas
      and melanocytic nevi excised only because of changes across time were inspected
      on a computer screen and assessed according to prospectively defined criteria.
      Lesions were stratified into 3 groups according to the length of follow-up.
      SETTING: Three hospital-based referral centers in Europe and Australia. Patients
      Four hundred sixty-one patients selected for digital dermoscopy monitoring. MAIN
      OUTCOME MEASURES: Description and comparison of dermoscopy features and changes
      in melanomas and melanocytic nevi at baseline and after follow-up. RESULTS: We
      inspected baseline and follow-up images of 499 melanocytic skin lesions from 461
      patients. The histopathologic diagnosis was melanoma in 91 cases and melanocytic
      nevus in 408. Most melanomas (58.2%; n = 53) were in situ, and the median
      thickness of invasive melanomas was 0.38 mm. Dermoscopy features of melanomas and
      nevi did not differ significantly at baseline. After follow-up of 1.5 to 4.5
      months, 61.8% of the melanomas showed no specific dermoscopy features for
      melanoma. This value declined to 45.0% after follow-up of 4.5 to 8.0 months and
      to 35.1% after more than 8.0 months. We could not differentiate melanomas and
      changing nevi by means of observed changes or dermoscopy features when follow-up
      was shorter than 4.5 months. With longer follow-up, melanomas tended to enlarge
      asymmetrically with architectural and color changes, and nevi tended to enlarge
      symmetrically without architectural and color changes. CONCLUSIONS: Sequential
      dermoscopy imaging detects incipient melanomas when they are still featureless.
      Interpretation of changes observed during follow-up depends on the length of
      follow-up.

PMID- 16982999
TI  - Dermoscopic patterns of acral melanocytic nevi and melanomas in a white
      population in central Italy.
AB  - OBJECTIVE: To investigate the dermoscopic features of acral melanocytic lesions
      in a white population in central Italy. DESIGN: Retrospective review. SETTING:
      University dermatology department. PATIENTS: Six hundred fifty-one Italian
      subjects, ranging in age from 6 months to 78 years. MAIN OUTCOME MEASURES: We
      retrospectively investigated all digital dermoscopic images of acral melanocytic
      lesions included in our database from January 1996 to May 2005. RESULTS: We
      retrieved digital images of 723 benign acral melanocytic lesions in 641 patients
      (235 males and 406 females; mean age, 26.5 years) and of 10 acral melanomas in 10
      patients (7 males and 3 females; mean age, 65 years). Individual lesions were
      located on the soles (n=520), fingers (n=146), and palms (n=67). Among acral
      nevi, the parallel furrow (42.1%) was the most common pattern, followed by the
      latticelike (14.9%), nontypical (13.7%), fibrillar (10.8%), homogeneous (9.3%),
      globular (5.4%), and reticular (2.1%) patterns. The frequency of distribution of
      the latticelike, nontypical, fibrillar, and homogeneous patterns significantly
      differed (P<.001, P=.03, P<.001, and P=.03, respectively) between anatomical
      sites. Also, 13 acral nevi (1.8%), mainly located on the fingers, showed a new
      combined pattern (transition pattern) consisting of a brownish black network
      associated with a parallel furrow or latticelike pattern. All 10 acral melanomas
      showed a multicomponent dermoscopic pattern. CONCLUSIONS: In our series of acral
      nevi, we observed 8 dermoscopic patterns, with varying distribution by anatomical
      site. Identification of a specific pattern is highly suggestive of the benign or
      the malignant nature of any given acral melanocytic lesion.

PMID- 16983000
TI  - Lymphoma risk in psoriasis: results of the PUVA follow-up study.
AB  - OBJECTIVE: To assess the risk of lymphoma in patients with psoriasis. DESIGN:
      Prospective cohort study that spans 30 years and a systematic review of the
      literature. SETTING: Sixteen university medical centers. PATIENTS: A total of
      1380 patients with psoriasis who were initially treated with psoralen-UV-A (PUVA)
      from 1975 through 1976 and who underwent periodic interviews and physician
      examinations irrespective of their use of any treatment. MAIN OUTCOME MEASURE:
      Incidence of lymphoma relative to that expected in the general US population
      (original primary end point of the study). RESULTS: The incidence of lymphoma in
      patients who received PUVA and were not exposed to high levels of methotrexate
      was comparable to that expected in the general population (incidence rate ratio,
      0.85; 95% confidence interval, 0.37-1.67) but was elevated among those exposed to
      high levels of methotrexate (> or =36 months) (incidence rate ratio, 4.39; 95%
      confidence interval, 1.59-12.06). CONCLUSION: Unless exposed to high levels of
      methotrexate, the risk of lymphoma among members of the PUVA Follow-up Study was
      comparable to that observed in the general population.

PMID- 16983001
TI  - 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of
      intertriginous psoriasis: a double-blind, randomized controlled study.
AB  - OBJECTIVE: During the last decades, management of intertriginous psoriasis (IP)
      has been unsatisfactory because of the adverse effects associated with long-term
      corticosteroid application and the lack of alternatives. Recently, both
      pimecrolimus and tacrolimus have been investigated for this indication and shown
      to be safe and effective. So far, to our knowledge, a comparison of one of these
      drugs with standard regimens for IP has not been performed. DESIGN: A single
      center, 4-week, double-blind, randomized, vehicle-controlled comparison study to
      assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1%
      betamethasone valerate in the treatment of IP. SETTING: Dermatologic hospital at
      Ruhr University of Bochum. PATIENTS: Eighty adults with IP. INTERVENTIONS:
      Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or
      the vehicle once daily for 28 days. MAIN OUTCOME MEASURES: Mean reduction of the
      Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of
      treatment was considered the primary outcome measure, which was analyzed on an
      intention-to-treat basis. The secondary outcome was a visual analog scale score
      for itching. RESULTS: After 4 weeks of treatment, the 3 active compounds and the
      vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1%
      betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and
      21.1% for vehicle). The 0.1% betamethasone was significantly more effective than
      1% pimecrolimus during the study period (P<.05). No significant difference was
      found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005%
      calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus
      decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1%
      pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for
      the corticosteroid (P<.05). CONCLUSIONS: The 1% pimecrolimus was shown to be less
      potent than 0.1% betamethasone in the treatment of IP. Considering the adverse
      effect profile of long-term application of corticosteroids, occasional or
      intermittent rescue therapy with short-term topical corticosteroids and
      maintenance with a less potent agent, such as 1% pimecrolimus or 0.005%
      calcipotriol, might be appropriate for patients with IP in general practice.

PMID- 16983002
TI  - Uniform resource locator decay in dermatology journals: author attitudes and
      preservation practices.
AB  - OBJECTIVES: To describe dermatology journal uniform resource locator (URL) use
      and persistence and to better understand the level of control and awareness of
      authors regarding the availability of the URLs they cite. DESIGN: Software was
      written to automatically access URLs in articles published between January 1,
      1999, and September 30, 2004, in the 3 dermatology journals with the highest
      scientific impact. Authors of publications with unavailable URLs were surveyed
      regarding URL content, availability, and preservation. MAIN OUTCOME MEASURES:
      Uniform resource locator use and persistence and author opinions and practices.
      RESULTS: The percentage of articles containing at least 1 URL increased from 2.3%
      in 1999 to 13.5% in 2004. Of the 1113 URLs, 81.7% were available (decreasing with
      time since publication from 89.1% of 2004 URLs to 65.4% of 1999 URLs) (P<.001).
      Uniform resource locator unavailability was highest in The Journal of
      Investigative Dermatology (22.1%) and lowest in the Archives of Dermatology
      (14.8%) (P=.03). Some content was partially recoverable via the Internet Archive
      for 120 of the 204 unavailable URLs. Most authors (55.2%) agreed that the
      unavailable URL content was important to the publication, but few controlled URL
      availability personally (5%) or with the help of others (employees, colleagues,
      and friends) (6.7%). CONCLUSIONS: Uniform resource locators are increasingly used
      and lost in dermatology journals. Loss will continue until better preservation
      policies are adopted.

PMID- 16983003
TI  - Wells syndrome in adults and children: a report of 19 cases.
AB  - BACKGROUND: Wells syndrome, an uncommon inflammatory dermatosis, is characterized
      by protean cutaneous manifestations, suggestive but not specific histopathologic
      findings, and usually a recurrent course. Because of its original description as
      a distinct entity, it has come to be regarded as an abnormal eosinophilic
      response to a number of causative agents. OBSERVATIONS: The medical records of 19
      patients (12 adults and 7 children) with Wells syndrome referred to the Institute
      of Dermatological Sciences from 1990 to 2005 were evaluated for the type and
      prevalence of skin lesions, clinical course and response to treatment, and
      possibly associated systemic symptoms, as well as histologic, laboratory, and
      immunofluorescence findings. The classic plaque-type variant proved to be the
      most common presentation in children but not in adults, who more frequently had
      the annular granuloma-like variant. Unilesional forms were found to occur more
      frequently in children. The course was recurrent, although slowly progressing,
      with a mean duration of disease of 5 years for adults and 3 years for children.
      CONCLUSIONS: We emphasize the concept that the diagnosis of Wells syndrome is a
      clinicopathologic diagnosis. Although it should be classified within a spectrum
      that includes multisystem eosinophilic disorders, such as Churg-Strauss and
      hypereosinophilic syndromes, Wells syndrome, which has 7 variants, is a distinct
      cutaneous disease lacking systemic involvement.

PMID- 16983004
TI  - Chronic recurrent lymphocytic Sweet syndrome as a predictive marker of
      myelodysplasia: a report of 9 cases.
AB  - BACKGROUND: Sweet syndrome is an acute neutrophilic dermatosis that occurs with
      malignant diseases, mainly myeloid hemopathies, in about 20% of cases. When
      associated with myelodysplasia, Sweet syndrome may be clinically atypical. It can
      be histologically unusual. Concomitant infiltration of mature neutrophils and
      immature myeloid cells has been reported, and its significance is still debated.
      In few patients, lymphocytic infiltrates are the presenting feature of Sweet
      syndrome with myelodysplasia. OBSERVATIONS: We present 9 male adult patients with
      chronic Sweet syndrome, all with recurrent eruptions of erythematous and annular
      plaques that were associated with relapsing polychondritis in 4 of the 9
      patients. Results from sequential biopsies showed that infiltrates were initially
      composed of lymphocytes and that neutrophilic dermal infiltration typical of
      Sweet syndrome occurred 24 to 96 months later, except in 2 cases. Moreover,
      atypical mononuclear cells were present on all initial biopsy specimens and
      strongly reacted to CD68 and myeloperoxidase, indicating a myeloid origin.
      Myelodysplastic syndrome occurred in all 9 patients, concomitantly with the
      neutrophilic infiltrate in 4 cases. CONCLUSIONS: Lymphocytic infiltrates with a
      clinical aspect of Sweet syndrome might represent the initial stage of a
      cutaneous dysgranulopoiesis syndrome and should lead to the research of atypical
      myeloid cells in skin infiltrate, blood, and bone marrow for the early detection
      of an associated myelodysplastic syndrome.

PMID- 16983005
TI  - Granulomatous skin infection caused by Malassezia pachydermatis in a dog owner.
AB  - BACKGROUND: Malassezia pachydermatis is part of the normal cutaneous microflora
      of dogs and many other mammals. M pachydermatis has not yet been reported as an
      agent that causes skin infection in humans, although it has been found to cause
      fungemia and other nosocomial infections in preterm newborns and
      immunocompromised adults. OBSERVATIONS: Malassezia pachydermatis was isolated
      from the facial granuloma of a healthy woman and her dog's skin scrapings and
      cerumen. The yeast identity was established by standard methods and scanning
      electron microscopy. A skin biopsy specimen showed chronic inflammatory
      granuloma, numerous purple-red round or ovoid spores in the superficial necrotic
      tissue, and sparse red spores in the dermis. The skin lesions healed after oral
      fluconazole and cryotherapy. CONCLUSIONS: Definite diagnosis of M pachydermatis
      induced skin infection principally depends on the results of fungal culture and
      histologic examination, and the combination of oral fluconazole and adjunctive
      cryotherapy seems to be an effective therapeutic regimen.

PMID- 16983006
TI  - What is meant by a "flare" in atopic dermatitis? A systematic review and
      proposal.
AB  - OBJECTIVE: To make preliminary recommendations for defining a flare of atopic
      dermatitis (AD) in clinical research based on a systematic review of the
      literature and experience in running clinical trials. DATA SOURCES: A sensitive
      electronic search of MEDLINE biographic database was conducted on April 19, 2005,
      using the following search terms: flare$, exacerbation$, relaps$, remission$,
      worse$, and *recurrence. The search was restricted to all prospective studies of
      AD in humans, using the Cochrane search terms for AD and prospective studies. In
      addition, we searched the literature on 3 chronic intermittent diseases (asthma,
      rheumatoid arthritis, and multiple sclerosis) to gain insight as to how other
      disciplines had tackled the definition of flares. DATA SYNTHESIS: A total of 401
      citations were reviewed, of which 16 articles (15 studies) were relevant. All
      were clinical trials. The definitions of disease flare or relapse in retrieved
      articles could be categorized into 3 broad themes: (1) composite definitions that
      include at least 2 different factors (eg, symptoms, severity duration, or
      treatment) (4 studies); (2) score thresholds or changes in severity scores (8
      studies); and (3) behavioral definitions, such as the use of rescue therapy (3
      studies). Only 1 investigative group (3 studies) used the same definition. None
      of the included studies were primarily designed to develop a definition of
      "flare." Evidence from other disciplines suggested at least 2 measures-totally
      controlled weeks and well-controlled weeks from asthma research-that could be
      used successfully in AD research. CONCLUSIONS: Defining an AD flare is a complex
      process, and this review has highlighted the need for standardization in defining
      measures of long-term disease control. We propose that a flare of AD be simply
      defined as an episode requiring escalation of treatment or seeking additional
      medical advice. Consideration should also be given to totally controlled weeks
      and well-controlled weeks to assess overall disease activity in patients with AD.
      Together, these definitions are intuitive, simple to use, and easy to understand.
      Future work is required to test the applicability of these recommendations in a
      variety of research settings.

PMID- 16983007
TI  - Two "positive" studies of probiotics for atopic dermatitis: or are they?

PMID- 16983008
TI  - Tacrolimus and pimecrolimus for atopic dermatitis: where do they fit in?

PMID- 16983009
TI  - Why perform dermoscopy? The evidence for its role in the routine management of
      pigmented skin lesions.

PMID- 16983010
TI  - Reflections on eosinophils and flame figures: where there's smoke there's not
      necessarily Wells syndrome.

PMID- 16983011
TI  - Ulcerated plaque in a 36-year-old woman. Tuberculosis verrucosa cutis.

PMID- 16983012
TI  - Cystic swelling overlying the upper sternum in a teenager. Bronchogenic cyst.

PMID- 16983013
TI  - Translucent nodular lesion of the penis. Apocrine hidrocystoma of the penis.

PMID- 16983014
TI  - A thick lichenified plaque on the ventral penile shaft. Penile porokeratosis of
      Mibelli.

PMID- 16983015
TI  - The 10 most commonly asked questions about dermatology maintenance of
      certification.

PMID- 16983016
TI  - Dermatology's role in treating sexually transmitted diseases.

PMID- 16983017
TI  - Compliance with sun protection following organ transplantation.

PMID- 16983018
TI  - Topical calcineurin inhibitors labeling: putting the "box" in perspective.

PMID- 16983019
TI  - Cost-effectiveness of Mohs micrographic surgery vs surgical excision for basal
      cell carcinoma of the face.

PMID- 16983020
TI  - Failure of etanercept therapy in disseminated granuloma annulare.

PMID- 16983021
TI  - Atypical early follicular graft-vs-host disease.

PMID- 16983022
TI  - Generalized milialike idiopathic calcinosis cutis.

PMID- 16983023
TI  - Campylobacter presenting as erythematous plaques on the lower extremity of a man
      with human immunodeficiency virus.

PMID- 16983024
TI  - Mycobacterium marinum infection cured by photodynamic therapy.

PMID- 16983025
TI  - Thelalgia in man: successful treatment with botulinum toxin.

PMID- 16983026
TI  - Pigmented lesions of the iris: common in patients, uncommon in dermatology
      textbooks.

PMID- 16983027
TI  - Dermoscopic color perspective.

PMID- 16983028
TI  - Inappropriate antibiotic use in soft tissue infections.
AB  - HYPOTHESIS: Many soft tissue infections treated with surgical drainage resolve
      even when treated with antibiotics not active against the organism isolated from
      the infection. DESIGN: Retrospective. SETTING: Integrated Soft Tissue Infection
      Services clinic. PATIENTS: All patients treated from July 19, 2000, to August 1,
      2001, who underwent surgical drainage of a soft tissue infection and had
      microbiological culture results. MAIN OUTCOME MEASURES: Documented resolution of
      the infection with drainage of the abscess and antibiotic therapy alone was
      deemed a cure. An infection resulting in death or other surgical therapy was
      deemed a failure. Therapy was appropriate when the organism was sensitive to
      prescribed antibiotics and was inappropriate when the organism was insensitive.
      RESULTS: The study included 376 patients with 450 infections. Staphylococcus
      aureus as the primary organism was isolated from 441 of the cultures. Methicillin
      sodium-sensitive S aureus and methicillin-resistant S aureus were found in 157
      and 284 of these isolates, respectively. Appropriate antibiotics were prescribed
      in 153 infections with methicillin-sensitive S aureus and in 25 with methicillin
      resistant S aureus. Of 441 episodes, 408 were clinically evaluated for cure.
      Three patients failed treatment, 2 in the appropriately treated group (resulting
      in death and amputation) and 1 patient with osteomyelitis in the inappropriately
      treated group. The cure rate for infections treated appropriately or
      inappropriately was the same. CONCLUSIONS: Treatment of soft tissue infections
      after surgical drainage, even with inappropriate antibiotics, has a high cure
      rate. Further studies to evaluate the efficacy of treating these infections
      without antibiotics are needed.

PMID- 16983029
TI  - Simplifying minimally invasive transhiatal esophagectomy with the inversion
      approach: Lessons learned from the first 20 cases.
AB  - HYPOTHESIS: The laparoscopic transhiatal esophagectomy can be simplified and
      performed safely and effectively by using a novel esophageal inversion technique.
      DESIGN: Case series describing technique, initial experience, and learning curve
      with laparoscopic inversion esophagectomy. SETTING: Tertiary care university
      hospital and veteran's hospital. PATIENTS: Twenty consecutive patients with high
      grade dysplasia (n = 16) and esophageal adenocarcinoma (n = 4). INTERVENTION:
      Laparoscopic inversion esophagectomy, a totally laparoscopic approach to
      transhiatal esophagectomy that incorporates distal to proximal inversion to
      improve mediastinal exposure and ease of dissection. MAIN OUTCOME MEASURES:
      Perioperative end points and complications, compared between the first and second
      groups of 10 patients. RESULTS: There were 19 men and 1 woman. Median operative
      time was 448 minutes. Median blood loss was 175 cm3. Median intensive care unit
      stay was 4 days, and median total hospital stay was 9 days. Overall anastomotic
      leak rate was 20%. Five patients developed an anastomotic stricture, all
      successfully managed with endoscopic dilation. There were 2 recurrent laryngeal
      nerve injuries, which resolved. There was no intraoperative or 30-day mortality.
      Between the first 10 consecutive cases and last 10 procedures, the incidence of
      anastomotic leak and stricture formation decreased from 30% to 10% and 40% to
      10%, respectively. During this period, the number of lymph nodes harvested
      increased 9-fold, and duration of intensive care unit stay decreased from 8.00 to
      2.50 days. CONCLUSIONS: Laparoscopic inversion esophagectomy is a safe procedure.
      The learning curve for the inversion approach is approximately 10 operations in
      the hands of esophageal surgeons with advanced laparoscopic expertise.

PMID- 16983030
TI  - Management and outcomes of isolated axillary node recurrence in breast cancer.
AB  - HYPOTHESIS: Management strategies affect the outcome of axillary recurrence in
      breast cancer. DESIGN: Population-based analysis. SETTING: Cancer agency breast
      cancer database. PATIENTS: Two hundred twenty women diagnosed with stage 0
      through III breast cancer between 1989 and 2003 who subsequently developed an
      isolated axillary relapse. MAIN OUTCOME MEASURES: Overall survival rate and
      disease-free survival rate according to treatment strategy of the axillary
      recurrence. RESULTS: Among 19 789 women diagnosed with stage 0 through III breast
      cancer during the study era, 220 had an isolated axillary recurrence (Kaplan
      Meier 5-year isolated axillary relapse rate, 1.0%). The median interval between
      primary breast cancer diagnosis and axillary recurrence was 2.2 years (range,1.8
      months to 11.9 years). Median follow-up time after axillary recurrence was 5.4
      years. Treatment for the axillary recurrence included lymph node biopsy (47.3%),
      complete axillary dissection (25.9%), axillary radiation (65.0%), chemotherapy
      (24.1%), and hormonal therapy (68.2%). The 5-year Kaplan-Meier overall survival
      rate estimate after axillary recurrence was 49.3% (95% confidence interval, 42.0
      56.3). Median survival time from the isolated axillary recurrence was 4.9 years
      (range, 2.0 months to 15.1 years). Overall (P < .001) and disease-free (P = .006)
      survival times were highest in those treated with a combination of surgery and
      radiation. Other factors associated with improved overall survival rate were an
      interval from diagnosis to relapse greater than 2.5 years (P = .003), no initial
      axillary radiation (P < .001), asymptomatic presentation of the recurrence (P =
      .05), and subsequent systemic treatment (P = .02). CONCLUSIONS: The 5-year
      isolated axillary recurrence rate of women treated for breast cancer was 1.0%.
      Multimodality management at the time of recurrence, including axillary surgery,
      radiation, and systemic therapy, significantly improved overall and disease-free
      survival.

PMID- 16983031
TI  - Surgical management of the groin lymph nodes in melanoma in the era of sentinel
      lymph node dissection.
AB  - HYPOTHESIS: Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL)
      has become an increasingly popular surgical technique for staging the regional
      lymph nodes in early-stage melanoma. The technique of LM/SL has potentially great
      advantage for the groin, where the morbidity of superficial groin dissection or
      iliac dissection can be high. The surgical management of these basins is unknown
      for patients with tumor-positive sentinel lymph nodes (SNs). DESIGN: Cohort of
      successive patients undergoing LM/SL over 18 years. Those patients found to have
      tumor-positive SNs underwent sentinel complete lymph node dissection.
      Postoperatively, patients were followed up on a routine basis with serial
      examinations and chest radiography. The median follow-up was 50 months. SETTING:
      Tertiary cancer center. PATIENTS: The technique of LM/SL was performed for 431
      consecutive patients. Sentinal lymph nodes were identified in each case. Patients
      with tumor-positive SNs underwent sentinel complete lymph node dissection.
      INTERVENTION: Cutaneous lymphoscintigraphy and blue dye with or without use of
      the gamma probe-directed LM/SL. Sentinel lymph nodes were examined by hematoxylin
      eosin staining and immunohistochemistry staining with HMB-45 and S100 protein.
      Only patients with tumor-positive SNs had sentinel complete lymph node
      dissection. Main Outcome Measure Computer-assisted database with statistical
      analyses using log-rank tests and Cox regression models. RESULTS: Of the 431
      patients, 264 (61%) were women and the median age was 50 years (age range, 15-89
      years). A majority (86%) of the primary tumors were on the lower extremities, 54%
      were of Clark level IV or V, and there was a mean +/- SD thickness of 1.89 +/-
      1.59 mm (range, 0.30-14.00 mm). Ninety-three patients (21%) were found to have
      tumor-positive SNs. After LM/SL and sentinel complete lymph node dissection, 62
      patients (67%) were found to have a single tumor-positive lymph node, 25 (27%)
      had 2 tumor-positive lymph nodes, and 6 (6%) had 3 or more tumor-positive lymph
      nodes. Only 12 patients (4%) with tumor-negative SNs have had recurrence in the
      dissected basin. The 5-year overall survival was significantly better for
      patients with tumor-negative lymph nodes (mean +/- SD 5-year overall survival,
      94% +/- 5%) than for patients with tumor-positive lymph nodes (mean +/- SD 5-year
      overall survival, 75% +/- 4%) (P < .01). The tumor status of the Cloquet lymph
      node was predictive of the tumor status of the iliac lymph nodes. Multivariate
      analyses with a Cox regression model identified tumor-positive SN (P = .001),
      primary tumor thickness (P = .03), and ulceration (P = .001) as being predictive
      of survival. Sex, age, Clark level, and primary site were not significant (P >
      .05). CONCLUSIONS: Our results demonstrate the prognostic significance of LM/SL
      for early-stage melanoma draining to the groin basin. The accuracy of LM/SL
      measured by the rare recurrences suggests that this surgical procedure should
      become standard for patients with early-stage melanoma of the lower extremities
      and trunk. Sampling of the Cloquet node should be used to determine the need for
      iliac dissection when a tumor-positive SN is identified in the groin.

PMID- 16983032
TI  - The effect of parathyroidectomy on bone fracture risk in patients with primary
      hyperparathyroidism.
AB  - BACKGROUND: Parathyroidectomy may increase bone density in primary
      hyperparathyroidism (PHPT), but it is unclear whether fracture risk is decreased.
      HYPOTHESIS: Parathyroidectomy decreases fracture risk. DESIGN: Retrospective
      cohort study with median follow-up of 6.5 years. SETTING: Twelve regional
      hospitals in California. PATIENTS: One thousand five hundred sixty-nine patients
      with PHPT. INTERVENTIONS: Parathyroidectomy or observation. Main Outcome Measure
      Fracture-free survival. RESULTS: Mean initial calcium, parathyroid hormone, and
      creatinine levels were 11.2 mg/dL (2.8 mmol/L), 123.0 pg/mL, and 0.9 mg/dL (79.6
      micromol/L), respectively. Parathyroidectomy was performed in 452 (28.8%)
      patients, and 1117 (71.2%) were observed. The 10-year fracture-free survival
      after PHPT diagnosis was 73% in patients treated with parathyroidectomy compared
      with 59% in those observed (hazard ratio [HR], 0.53; 95% confidence interval
      [CI], 0.38-0.73; P < .001). Parathyroidectomy decreased the 10-year hip fracture
      rate by 8% (P = .001) and the upper extremity fracture rate by 3% (P = .02).
      Parathyroidectomy was independently associated with a decreased fracture risk
      (HR, 0.68; 95% CI, 0.47-0.98), whereas female sex (HR, 1.82; 95% CI, 1.19-2.80)
      and increased creatinine level (HR per 1-mg/dL [88.4-micromol/L] increment, 2.05;
      95% CI, 1.22-3.46) remained independently associated with an increased fracture
      risk. Age of 50 years or older (HR, 1.62; 95% CI, 0.99-2.66), initial parathyroid
      hormone level (HR, 1.00; 95% CI, 0.99-1.02), and calcium level (HR, 1.02; 95% CI,
      0.75-1.37) were not independently associated with fracture risk after adjusting
      for all other variables. CONCLUSIONS: Parathyroidectomy is associated with a
      decreased risk of fracture in PHPT. The largest decrease was in hip fractures.
      Parathyroidectomy should be considered for all patients with PHPT to reduce
      fracture risk, regardless of age or calcium or parathyroid hormone levels.

PMID- 16983033
TI  - Laparoscopic-assisted pancreatic necrosectomy: A new surgical option for
      treatment of severe necrotizing pancreatitis.
AB  - HYPOTHESIS: Open surgery for pancreatic debridement is often associated with
      major morbidity such as wound complications, fascial dehiscence, and intestinal
      fistulae. Hand-assisted laparoscopic surgery (HALS) is useful for complex
      abdominal procedures since the benefits of traditional laparoscopic surgery are
      retained. Published experience with HALS for pancreatic debridement is limited to
      anecdotal case reports. SETTING: University-affiliated private and public
      hospitals. PATIENTS: Twenty-three patients with necrotizing pancreatitis were
      evaluated and 19 patients underwent pancreatic debridement from 2001 to 2006. A
      GelPort (Applied Medical, Rancho Santa Margarita, Calif) was used to provide
      laparoscopic hand access. In the majority of the patients, an infracolic approach
      was used to access the pancreatic necrosis. RESULTS: Nineteen patients underwent
      laparoscopic evacuation of pancreatic necrosis, and in 18 patients, the procedure
      was completed. The mean age was 54 years; the mean +/- SEM body mass index,
      calculated as weight in kilograms divided by height in meters squared, was 32.0
      +/- 2.6; the mean American Society of Anesthesiologists score was 3.4; and 7 of
      19 patients had past history organ failure. The mean +/- SEM operating time was
      153 +/- 10 minutes and mean +/- SEM blood loss was 352.6 +/- 103 mL. Four
      patients required reoperations, 2 using HALS and 2 open. There were no
      postoperative complications related to the HAL procedure itself, such as major
      wound infections, intestinal fistulae, or postoperative hemorrhage. Postoperative
      computed tomographic scans confirmed adequacy of debridement. The mean +/- SEM
      length of hospital stay after surgery was 16.3 +/- 3.8 days. CONCLUSIONS: This is
      the largest reported study of laparoscopic debridement for pancreatic necrosis.
      The procedure is feasible and associated with a low morbidity and mortality.
      Pancreatic debridement with HALS may provide a new option for the surgical
      treatment of selected patients with severe necrotizing pancreatitis.

PMID- 16983034
TI  - Factors affecting long-term mortality after endovascular repair of abdominal
      aortic aneurysms.
AB  - HYPOTHESIS: Endovascular repair of abdominal aortic aneurysms has made
      considerable advancements with respect to perioperative mortality. However, fewer
      data are available regarding factors affecting long-term mortality, including the
      impact of adverse perioperative cardiac events. Perioperative clinical cardiac
      risk factors are significant predictors of long-term mortality. DESIGN, SETTING,
      AND PATIENTS: Retrospective review of a prospective database of 468 patients who
      underwent endovascular abdominal aortic aneurysm repair from June 3, 1996, to
      January 31, 2005. MAIN OUTCOME MEASURES: Preoperative, intraoperative, and
      postoperative factors were analyzed using multivariate Cox proportional hazards
      models to identify statistically significant independent predictors of long-term
      survival (beyond 30 days and after discharge from the hospital). RESULTS: The
      mean age was 74 years, and 90% of the patients were male. Median follow-up was
      2.57 years (interquartile range, 0.92-4.06 years). The leading cause of death was
      cardiac in nature. On multivariate analysis, the number of preoperative clinical
      cardiac risk factors (P < .001), spending 2 or more days in the intensive care
      unit (P < .001), and having an ST-segment elevation myocardial infarction (P <
      .001) were predictors of decreased long-term survival. Of note, having a
      perioperative non-ST-segment elevation myocardial infarction was not predictive
      of decreased survival (P = .09). CONCLUSIONS: Adverse cardiac events are the
      leading cause of long-term mortality following endovascular repair of abdominal
      aortic aneurysms. Preoperative clinical cardiac risk factors are significant
      predictors of long-term mortality, as are a prolonged intensive care unit stay
      and a perioperative ST-segment elevation myocardial infarction. A perioperative
      non-ST-segment elevation myocardial infarction did not influence long-term
      outcome.

PMID- 16983035
TI  - Prosthetic replacement of the infrahepatic inferior vena cava for leiomyosarcoma.
AB  - HYPOTHESIS: Resection of the infrahepatic inferior vena cava associated with
      prosthetic graft replacement for caval leiomyosarcoma is an acceptable procedure
      to obtain prolonged and good-quality survival. DESIGN: A consecutive sample
      clinical study with a mean follow-up of 40 months. SETTING: The surgical
      department of an academic tertiary center and an affiliated secondary care
      center. PATIENTS: Eleven patients, with a mean age of 51 years, who have primary
      leiomyosarcoma of the infrahepatic inferior vena cava. INTERVENTIONS: All of the
      patients underwent radical resection of the tumor en bloc with the affected
      segment of the vena cava. Reconstruction consisted of 10 cavocaval
      polytetrafluoroethylene grafts and 1 cavobiliac graft. An associated right
      nephrectomy was performed in 2 cases. The left renal vein was reimplanted in the
      graft in 3 cases. MAIN OUTCOME MEASURES: Cumulative disease-specific survival,
      disease-free survival, and graft patency rates expressed by standard life-table
      analysis. RESULTS: No patients died in the postoperative period. The cumulative
      (SE) disease-specific survival rate was 53% (21%) at 5 years. The cumulative (SE)
      disease-free survival rate was 44% (19%) at 5 years. The cumulative (SE) graft
      patency rate was 67% (22%) at 5 years. CONCLUSION: Radical resection followed by
      prosthetic graft reconstruction is a valuable method for treating primary
      leiomyosarcoma of the infrahepatic inferior vena cava.

PMID- 16983036
TI  - Impact of inguinal hernia repair on family and other informal caregivers.
AB  - HYPOTHESIS: Inguinal hernia significantly affects family and other informal
      caregivers, and hernia repair will significantly reduce caregiver burden.
      METHODS: We analyzed data from a Veterans Affairs Cooperative Study with mixed
      models to compare the level of burden among caregivers of inguinal hernia
      patients from preoperative measurement to measurement at 2 weeks and at 3 months
      postoperatively. RESULTS: Most caregivers were wives (73%) and lived with the
      patients (88%). There were no differences in caregiver burden by type of
      treatment. The time caregivers spent assisting patients increased significantly
      over the 2 weeks following treatment (odds ratio, 4.34). In contrast, 3 months
      after treatment, caregivers reported spending less time on additional chores than
      before treatment (odds ratio, 0.12). Furthermore, caregivers' concerns about
      patients' abilities to perform normal household activities decreased by 2 weeks
      posttreatment (odds ratio, 0.52). Wives/girlfriends and caregivers of patients
      with complications were more likely to report these concerns. CONCLUSIONS:
      Inguinal hernia and its repair significantly affect informal caregivers.
      Caregivers assumed the heaviest time and effort-related burden 2 weeks following
      hernia repair and expended additional effort if the patient experienced
      complications. Interventions should reflect when burden is greatest and target
      the subgroups of caregivers who most need support.

PMID- 16983037
TI  - Wrong-side/wrong-site, wrong-procedure, and wrong-patient adverse events: Are
      they preventable?
AB  - HYPOTHESIS: Wrong-side/wrong-site, wrong-procedure, and wrong-patient adverse
      events (WSPEs) are devastating, unacceptable, and often result in litigation, but
      their frequency and root causes are unknown. Wrong-side/wrong-site, wrong
      procedure, and wrong-patient events are likely more common than realized, with
      little evidence that current prevention practice is adequate. DESIGN: Analysis of
      several databases demonstrates that WSPEs occur across all specialties, with high
      numbers noted in orthopedic and dental surgery. Databases analyzed included: (1)
      the National Practitioner Data Bank (NPDB), (2) the Florida Code 15 mandatory
      reporting system, (3) the American Society of Anesthesiologists (ASA) Closed
      Claims Project database, and (4) a novel Web-based system for collecting WSPE
      cases (http://www.wrong-side.org). RESULTS: The NPDB recorded 5940 WSPEs (2217
      wrong-side surgical procedures and 3723 wrong-treatment/wrong-procedure errors)
      in 13 years. Florida Code 15 occurrences of WSPEs number 494 since 1991,
      averaging 75 events per year since 2000. The ASA Closed Claims Project has
      recorded 54 cases of WSPEs. Analysis of WSPE cases, including WSPE cases
      submitted to http://www.wrong-side.org, suggest several common causes of WSPEs
      and recurrent systemic failures. Based on these findings, we estimate that there
      are 1300 to 2700 WSPEs annually in the United States. Despite a significant
      number of cases, reporting of WSPEs is virtually nonexistent, with reports in the
      lay press far more common than reports in the medical literature. Our research
      suggests clear factors that contribute to the occurrence of WSPEs, as well as
      ways to reduce them. CONCLUSIONS: Wrong-side/wrong-site, wrong-procedure, and
      wrong-patient adverse events, although rare, are more common than health care
      providers and patients appreciate. Prevention of WSPEs requires new and
      innovative technologies, reporting of case occurrence, and learning from
      successful safety initiatives (such as in transfusion medicine and other high
      risk nonmedical industries), while reducing the shame associated with these
      events.

PMID- 16983038
TI  - Image of the month: Schwannoma.

PMID- 16983039
TI  - Image of the month: Abdominal cocoon.

PMID- 16983040
TI  - Steroids and the intensive care unit.

PMID- 16983041
TI  - Corticosteroids in critically ill patients: A long and winding road.

PMID- 16983042
TI  - Using corticosteroids in intensive care.

PMID- 16983043
TI  - Ablative therapy of malignant liver neoplasm.

PMID- 16983044
TI  - Sleep and health: Everywhere and in both directions.

PMID- 16983045
TI  - Sleep duration and health in young adults.
AB  - BACKGROUND: Both long and short sleep durations have been associated with
      negative health outcomes in middle-aged and older adults. This study assessed the
      relationship between sleep duration and self-rated health in young adults.
      METHODS: Using anonymous questionnaires, data were collected from 17 465
      university students aged 17 to 30 years who were taking non-health-related
      courses at 27 universities in 24 countries. The response rate was greater than
      90%. Sleep duration was measured by self-report; the health outcome was self
      rated health; and age, sex, socioeconomic background, smoking, alcohol
      consumption, body mass index, physical activity, depression (Beck Depression
      Inventory), recent use of health services, and country of origin were included as
      covariates. RESULTS: Sixty-three percent of respondents slept for 7 to 8 hours;
      21% were short sleepers (6%, <6 hours; 15%, 6-7 hours); and 16% were long
      sleepers (10%, 8-10 hours; 6%, >10 hours). Compared with the reference category
      (7-8 hours), the adjusted odds ratio of poor health was 1.56 (95% confidence
      interval [CI], 1.22-1.99) for respondents sleeping 6 to 7 hours and 1.99 (95% CI,
      1.31-3.03) for those sleeping less than 6 hours. The same significant pattern was
      seen when the results were analyzed separately by sex. When respondents from
      Japan, Korea, and Thailand (characterized by relatively short sleep durations)
      were excluded, the adjusted odds ratios were 1.33 (95% CI 1.03-1.73) and 1.62
      (95% CI, 1.06-2.48) for those sleeping 6 to 7 hours and less than 6 hours,
      respectively. There were no significant associations between self-rated health
      and long sleep duration. CONCLUSION: Our data suggest that short sleep may be
      more of a concern than long sleep in young adults.

PMID- 16983046
TI  - Shift of monocyte function toward cellular immunity during sleep.
AB  - BACKGROUND: Sleep is considered to strengthen immune defense. We hypothesized
      that sleep achieves this effect by shifting the balance between types 1 and 2
      cytokine activity toward increased type 1 activity, thereby supporting adaptive
      cellular immune responses. METHODS: We analyzed monocyte-derived type 1
      (interleukin 12 [IL-12]) and type 2 (IL-10) cytokines by means of multiparametric
      flow cytometry in healthy human subjects (n = 11) during a regular sleep-wake
      cycle and 24 hours of wakefulness. RESULTS: Sleep increased the number of IL-12
      producing monocytes and concurrently decreased the number of IL-10-producing
      monocytes, thereby inducing clear rhythms in these cells, with maximum numbers at
      2:20 and 11:30 am, respectively. The rhythms were completely absent during
      continuous wakefulness. Correlation analyses and supplementary in vitro studies
      suggest that high prolactin and low cortisol levels are factors contributing to
      the shift in the IL-12/IL-10 ratio toward increased IL-12 activity during sleep.
      CONCLUSIONS: Monocyte-derived IL-12 and IL-10 play a critical role for tuning the
      synapse between antigen-presenting cells and lymphocytes. By preferentially
      supporting type 1 IL-12 activity, sleep induces a 24-hour oscillation between
      predominant types 1 and 2 cytokines and, in this way, acts to globally increase
      the efficacy of adaptive immune responses. Improving sleep could represent a
      therapeutic option to enhance the success of vaccinations and success in the
      treatment of diseases (eg, atopic dermatitis and human immunodeficiency virus
      infection) that are characterized by type 2 cytokine overactivity.

PMID- 16983047
TI  - Sleep duration and body mass index in a rural population.
AB  - BACKGROUND: A growing body of epidemiological evidence suggests an association
      between short sleep duration and obesity. Recently, potential hormonal links have
      been observed that may account for the relationship. The possible connection
      between sleep duration and body mass index (BMI) has not been explored in rural
      populations. Rural populations are of interest because obesity rates are high and
      lifestyle patterns of nutrition, physical activity, work hours, and sleep may
      differ from those in urban and suburban populations. We conducted this study to
      determine whether short sleep duration is related to BMI and obesity in a rural
      population in southeast Iowa. METHODS: We conducted a cross-sectional analysis of
      data collected in the Keokuk County Rural Health Cohort Study, 1999-2004. Study
      participants were from a population-based sample consisting of 990 employed
      adults in a rural community in southeastern Iowa. The main outcome measure was
      BMI. Multiple linear regression modeling was used to adjust for potential
      confounding variables. RESULTS: Self-reported sleep duration on weeknights was
      negatively correlated (beta = -0.42; 95% confidence interval, -0.77 to -0.07)
      with higher BMI after adjusting for sex, age, educational achievement, physical
      job demand, household income, depressive symptoms, marital status, alcohol
      consumption, and snoring. CONCLUSION: These data support an association between
      short sleep duration and higher BMI in this rural population, which is consistent
      with the relationship found in other settings.

PMID- 16983048
TI  - Longitudinal association of sleep-related breathing disorder and depression.
AB  - BACKGROUND: Sleep-related breathing disorder (SRBD) and depression have each been
      independently associated with substantial morbidity, impairment, and disability.
      The development of clinical strategies for screening and managing depression in
      patients with SRBD requires elucidation of the association between the 2
      conditions. This population-based epidemiological study assesses SRBD as a
      longitudinal predictor of depression. METHODS: Men (n = 788) and women (n = 620)
      randomly selected from a working population were evaluated for SRBD by in
      laboratory polysomnography and for depression by the Zung depression scale.
      Results of multiple studies, performed at 4-year intervals, were available for
      most participants. Sleep-related breathing disorder was characterized by the
      apnea-hypopnea index (AHI; events per hour) categories: AHI = 0, no SRBD; 0 < AHI
      < 5, minimal SRBD; 5 < or = AHI < 15, mild SRBD; and AHI > or = 15, moderate or
      worse SRBD. Depression was defined as a score of 50 or higher on the Zung scale
      or use of antidepressants. Potential confounding, interacting, and mediating
      factors were assessed by clinical measurements and questionnaires. RESULTS: In
      purely longitudinal models, an increase of 1 SRBD category (eg, from minimal to
      mild SRBD) was associated with a 1.8-fold (95% confidence interval, 1.3-2.6)
      increased adjusted odds for development of depression. In adjusted models
      combining longitudinal and cross-sectional associations, compared with
      participants with no SRBD, the odds for development of depression were increased
      by 1.6-fold (95% confidence interval, 1.2-2.1) in participants with minimal SRBD,
      by 2.0-fold (95% confidence interval, 1.4-2.9) in participants with mild SRBD,
      and by 2.6-fold (95% confidence interval, 1.7-3.9) in those with moderate or
      worse SRBD. CONCLUSION: Our longitudinal findings of a dose-response association
      between SRBD and depression provide evidence consistent with a causal link
      between these conditions and should heighten clinical suspicion of depression in
      patients with SRBD.

PMID- 16983049
TI  - Sleepiness and sleep in patients with both systolic heart failure and obstructive
      sleep apnea.
AB  - BACKGROUND: Adverse effects of obstructive sleep apnea (OSA), including sleep
      deprivation, can contribute to the progression of heart failure. The usual
      indication to diagnose and treat sleep apnea is subjective sleepiness. Previous
      studies suggest that patients with both heart failure and obstructive sleep apnea
      often do not complain of sleepiness, albeit their sleep time may be reduced.
      Therefore, we tested the hypothesis that patients with heart failure have less
      sleepiness and sleep less compared with subjects without heart failure for a
      given severity of OSA. METHODS: Sleepiness assessed with the Epworth Sleepiness
      Scale and sleep structure measured with polysomnography were compared among 155
      consecutive patients with heart failure and from a random community sample (n =
      1139) according to categories of the apnea-hypopnea index (<5, no OSA; 5-14, mild
      OSA; and > or =15, moderate to severe OSA). RESULTS: Compared with the community
      sample, for any given severity of OSA, patients with heart failure had lower mean
      +/- SE Epworth Sleepiness Scale scores (7.1 +/- 0.4 vs 8.3 +/- 0.2 [P = .005];
      6.7 +/- 0.7 vs 9.2 +/- 0.3 [P < .001]; and 7.8 +/- 0.7 vs 9.8 +/- 0.4 [P = .01]),
      indicating less sleepiness despite sleeping less (total sleep time mean +/- SE
      [in minutes]: 306 +/- 7 vs 384 +/- 2, 295 +/- 19 vs 384 +/- 5, and 285 +/- 13 vs
      359 +/- 7 for no, mild, and moderate to severe OSA, respectively; P < .001 for
      all comparisons). CONCLUSIONS: Patients with heart failure have less subjective
      daytime sleepiness compared with individuals from a community sample, despite
      significantly reduced sleep time, whether or not they have OSA. In patients with
      heart failure, the absence of subjective sleepiness is not a reliable means of
      ruling out OSA.

PMID- 16983050
TI  - Soluble interleukin 6 receptor: A novel marker of moderate to severe sleep
      related breathing disorder.
AB  - BACKGROUND: Given the previously described association between sleep-related
      breathing disorder (SRBD) and markers of inflammation, we assessed the
      relationship of SRBD with levels of both interleukin 6 (IL-6) and soluble IL-6
      receptor (sIL-6R), a marker with more expansive physiologic effects than IL-6.
      The objectives were to explore the relationship between moderate to severe sleep
      apnea with IL-6 and sIL-6R levels and to examine morning and evening variability
      for each cytokine. METHODS: A total of 385 adult participants (> or =18 years of
      age) in the Cleveland Family Study, Cleveland, Ohio, underwent sleep studies and
      determination of IL-6 and sIL-6R levels in samples obtained in the evening and
      morning of polysomnography. Moderate to severe SRBD was defined as a respiratory
      disturbance index greater than or equal to 30. RESULTS: The subjects were aged
      44.9 +/- 16.7 (mean +/- SD) years, 44% were male, and 48% were African American,
      with a body mass index (weight in kilograms divided by the height in meters
      squared) of 32.5 +/- 8.1 (mean +/- SD). Linear regression analysis showed that
      after adjustment for subject characteristics, waist circumference, and
      comorbidities, SRBD was not significantly associated with morning IL-6 levels. In
      contrast, linear regression analyses showed that, compared with the participants
      without SRBD, those with SRBD had significantly higher morning sIL-6R levels
      (mean +/- SD, 4.60 +/- 1.42 ng/mL [P = .001]), even after adjustment for subject
      characteristics, waist circumference, and comorbidities, which persisted after
      adjustment of evening sIL-6R levels. CONCLUSIONS: Morning sIL-6R levels
      demonstrated stronger associations with moderate to severe SRBD than morning IL-6
      levels. Associations with SRBD and morning sIL-6R levels persisted even after
      adjustment for waist circumference, cardiovascular disease, and evening sIL-6R
      levels, suggesting the potential utility of sIL-6R as a marker for measuring
      overnight SRBD stresses. Further investigation of this biomarker may provide
      insight into SRBD-related inflammation.

PMID- 16983051
TI  - Consequences of comorbid insomnia symptoms and sleep-related breathing disorder
      in elderly subjects.
AB  - BACKGROUND: The prevalence of sleep-related breathing disorder (SRBD) and
      insomnia symptoms increases considerably with advancing age, but little is known
      about their cooccurrence and their effects on daytime functioning when present
      together. METHODS: Older adults with (cases, n = 99) and without (controls, n =
      100) symptoms of insomnia underwent 2 nights of in-laboratory polysomnography,
      daytime nap, and neurobehavioral testing and completed study questionnaires.
      Predictors of SRBD were identified (apnea-hypopnea index [indicating number of
      events per hour], > or =15). Participants were divided into 4 groups--with and
      without insomnia and with and without SRBD--and the groups were compared on
      measures of daytime functioning. RESULTS: Cases had a lower rate of SRBD (29.3%)
      than controls (38.0%). Body mass index (calculated as weight in kilograms divided
      by height in meters squared) of 30 or higher, neck circumference greater than
      15.5 inches, and a history of "loud snoring" or "stops breathing, chokes, or
      struggles for breath" were independently predictive of SRBD in participants with
      insomnia symptoms. Having both insomnia symptoms and SRBD was associated with
      significantly lower daytime functioning and longer psychomotor reaction times
      compared with having neither condition. CONCLUSION: Because insomnia comorbid
      with SRBD is associated with the greatest functional impairment, and SRBD is
      commonly found in the elderly population, health care providers should also
      consider SRBD in elderly patients with insomnia symptoms.

PMID- 16983052
TI  - Plasma levels of tumor necrosis factor alpha and soluble tumor necrosis factor
      receptors in patients with narcolepsy.
AB  - BACKGROUND: Narcolepsy is a disabling sleep disorder characterized by excessive
      daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis.
      Recent studies suggest that the immune system might play a pathogenic role
      pointing to a possible involvement of inflammatory cytokines. METHODS: We
      investigated a sample of 30 patients with narcolepsy in comparison with 120 sex-
      and age-matched and 101 sex-, body mass index (BMI)-, and age-matched randomly
      selected normal controls. In these groups, plasma concentrations of tumor
      necrosis factor alpha (TNF-alpha) and its soluble receptors p55 and p75 (soluble
      TNF receptor [sTNF-R] p55 and sTNF-R p75) were measured using commercial enzyme
      linked immunosorbent assays. RESULTS: The narcoleptic patients showed a
      significantly higher BMI compared with controls of the same age. Soluble TNF-R
      p75 levels were consistently elevated in the narcoleptic patients compared with
      their sex- and age-matched (P = .001) as well as sex-, BMI-, and age-matched
      counterparts (P = .003). Female narcoleptic patients exhibited higher sTNF-R p55
      levels compared with their sex- and age-matched controls (P = .01), but this
      difference disappeared when comparing patients with sex-, BMI-, and age-matched
      normal controls. Tumor necrosis factor alpha levels did not differ significantly
      between groups. CONCLUSION: Narcoleptic patients show increased plasma levels of
      sTNF-R p75, suggesting a functional alteration of the TNF-alpha cytokine system,
      further corroborating a possible pathogenic role of the immune system in this
      sleep disorder.

PMID- 16983053
TI  - Allergic rhinitis and its consequences on quality of sleep: An unexplored area.
AB  - BACKGROUND: Allergic rhinitis (AR) is common and has been shown to impair social
      life and sleep. Patients with severe symptoms may have more sleep disturbances
      than those with a mild form of the disease, but this has never been assessed
      using a validated tool. The objective of our study was to assess, in patients
      with AR, whether duration and severity of AR are associated with sleep
      impairment. METHODS: A nationwide controlled cross-sectional epidemiological
      study was carried out. A representative sample of 260 French ear, nose, and
      throat and allergy specialists enrolled 591 patients with AR of at least 1 year's
      duration. Sleep disorders, sleep quality, and AR were assessed using validated
      tools (Sleep Disorders Questionnaire, Epworth Sleepiness Scale, and Score for
      Allergic Rhinitis). The severity of AR was assessed using the Allergic Rhinitis
      and its Impact on Asthma classification. RESULTS: All dimensions of sleep were
      impaired by AR, particularly by the severe type. Sleep was significantly more
      impaired in patients with severe AR than in those with the mild type. The
      duration of AR (intermittent or persistent) had no effect on sleep. CONCLUSION:
      These data underline the close relationship between AR and sleep and highlight
      the need for clinicians, particularly general practitioners, to be attentive in
      this respect.

PMID- 16983054
TI  - Impact of a child's chronic illness on maternal sleep and daytime functioning.
AB  - BACKGROUND: Chronic illness may not only directly impact the sleep of a patient
      but also indirectly impact the sleep of the family members who provide nighttime
      care. For parents of children with chronic illnesses, few studies have examined
      sleep disruptions that may account for elevated rates of depression and fatigue.
      Our objectives were to examine sleep patterns and causes of sleep disturbances in
      caregivers of children with and without chronic illnesses and to determine
      whether sleep mediates the relationship between a child's chronic illness and
      daytime functioning in caregivers. METHODS: A total of 118 mothers of children
      with ventilator dependency (VENT), cystic fibrosis (CF), or healthy children
      (HEALTHY) completed a series of self-reported measures during a structured
      telephone interview, including the Pittsburgh Sleep Quality Index, the 24-Hour
      Sleep Patterns Interview, the Child Health Questionnaire-General Health Scale,
      the Center for Epidemiological Studies-Depression Scale, and the Iowa Fatigue
      Scale. RESULTS: Ventilator dependency caregivers reported an earlier morning wake
      time and shorter total sleep time than both CF and HEALTHY caregivers. In
      addition, VENT caregivers reported more night wakings and poorer sleep quality
      than HEALTHY caregivers. Frequent sleep disruptions for VENT caregivers were due
      to nighttime caregiving, while almost 40% of both VENT and CF caregivers reported
      sleep disruptions due to stress related to their child's health. Finally,
      caregiver sleep quality was found to mediate the relationship between child
      health and caregiver depression and fatigue. CONCLUSIONS: Sleep in caregivers of
      children with chronic illnesses, in particular ventilator dependency, is
      significantly disrupted, resulting in chronic partial sleep deprivation. Owing to
      the level of attention and care required by these children, interventions and
      support for caregivers to improve their sleep quality and quantity are necessary.

PMID- 16983055
TI  - Sleep deprivation and activation of morning levels of cellular and genomic
      markers of inflammation.
AB  - BACKGROUND: Inflammation is associated with increased risk of cardiovascular
      disorders, arthritis, diabetes mellitus, and mortality. The effects of sleep loss
      on the cellular and genomic mechanisms that contribute to inflammatory cytokine
      activity are not known. METHODS: In 30 healthy adults, monocyte intracellular
      proinflammatory cytokine production was repeatedly assessed during the day across
      3 baseline periods and after partial sleep deprivation (awake from 11 pm to 3
      am). We analyzed the impact of sleep loss on transcription of proinflammatory
      cytokine genes and used DNA microarray analyses to characterize candidate
      transcription-control pathways that might mediate the effects of sleep loss on
      leukocyte gene expression. RESULTS: In the morning after a night of sleep loss,
      monocyte production of interleukin 6 and tumor necrosis factor alpha was
      significantly greater compared with morning levels following uninterrupted sleep.
      In addition, sleep loss induced a more than 3-fold increase in transcription of
      interleukin 6 messenger RNA and a 2-fold increase in tumor necrosis factor alpha
      messenger RNA. Bioinformatics analyses suggested that the inflammatory response
      was mediated by the nuclear factor kappaB inflammatory signaling system as well
      as through classic hormone and growth factor response pathways. CONCLUSIONS:
      Sleep loss induces a functional alteration of the monocyte proinflammatory
      cytokine response. A modest amount of sleep loss also alters molecular processes
      that drive cellular immune activation and induce inflammatory cytokines; mapping
      the dynamics of sleep loss on molecular signaling pathways has implications for
      understanding the role of sleep in altering immune cell physiologic
      characteristics. Interventions that target sleep might constitute new strategies
      to constrain inflammation with effects on inflammatory disease risk.

PMID- 16983056
TI  - A double-blind, placebo-controlled, crossover study of sildenafil in obstructive
      sleep apnea.
AB  - BACKGROUND: Sildenafil prolongs the action of cyclic guanosine monophosphate and
      nitric oxide by inhibiting cyclic guanosine monophosphate-specific
      phosphodiesterase 5. It is largely used for erectile dysfunction, a highly
      prevalent condition in obstructive sleep apnea. Because nitric oxide promotes
      upper airway congestion, muscle relaxation, and pulmonary vasodilation, the aim
      of this study was to establish the impact of a single 50-mg dose of sildenafil on
      the sleep of patients with severe obstructive sleep apnea. METHODS: Thirteen
      [corrected] middle-aged men with severe obstructive sleep apnea were
      consecutively selected for this double-blind, placebo-controlled, crossover
      study. Exclusion criteria were obesity, cardiovascular and/or respiratory
      disease, and conditions that interfere with sleep. All-night polysomnography was
      preceded by a single 50-mg dose of sildenafil or matching placebo randomly
      administered at bedtime, after a washout period of 1 week. RESULTS: In comparison
      to placebo, a single 50-mg dose of sildenafil significantly increased the
      percentage of total sleep time with an arterial oxygen saturation of less than
      90% (mean +/- SD, 15.6% +/- 9.6% vs 7.9% +/- 3.3%, [corrected] P < .01), without
      a difference in the nadir of oxygen desaturation. The mean arterial oxygen
      saturation also decreased (92.1% +/- 1.9% vs 93.8% +/- 1.3%, P = .03),
      [corrected] and the desaturation index increased (30.3 +/- 14.5 [corrected]
      events per hour vs 18.5 +/- 9.1 [corrected] events per hour, P < .001). There was
      an increase in apnea-hypopnea index (48.1 +/- 20.8 [corrected] events per hour vs
      32.3 +/- 11.3 [corrected] events per hour, P = .001), [corrected] involving
      mostly obstructive events. CONCLUSION: In patients with severe obstructive sleep
      apnea, a single 50-mg dose of sildenafil at bedtime worsens respiratory and
      desaturation events.

PMID- 16983057
TI  - Role of sleep duration and quality in the risk and severity of type 2 diabetes
      mellitus.
AB  - BACKGROUND: Evidence from laboratory and epidemiologic studies suggests that
      decreased sleep duration or quality may increase diabetes risk. We examined
      whether short or poor sleep is associated with glycemic control in African
      Americans with type 2 diabetes mellitus. METHODS: We conducted a cross-sectional
      study of volunteers with type 2 diabetes interviewed at the University of Chicago
      Hospitals, Chicago, Ill. The final analysis included 161 participants. Glycemic
      control was assessed by hemoglobin A1c (HbA1c) level obtained from medical
      charts. Sleep quality was assessed using the Pittsburgh Sleep Quality Index
      (PSQI). Perceived sleep debt was calculated as the difference between preferred
      and actual weekday sleep duration. RESULTS: The mean +/- SD sleep duration was
      6.0 +/- 1.6 hours, and 71% of the participants were classified as having poor
      quality sleep (PSQI score >5). We excluded patients with sleep frequently
      disrupted by pain (n = 39). In patients without diabetic complications, glycemic
      control was associated with perceived sleep debt but not PSQI score. The
      predicted increase in HbA1c level for a perceived sleep debt of 3 hours per night
      was 1.1% above the median. In patients with at least 1 complication, HbA1c level
      was associated with PSQI score but not perceived sleep debt. The predicted
      increase in HbA1c level for a 5-point increase in PSQI was 1.9% above the median.
      CONCLUSIONS: In our sample, sleep duration and quality were significant
      predictors of HbA1c, a key marker of glycemic control. Combined with existing
      evidence linking sleep loss to increased diabetes risk, these data suggest that
      optimizing sleep duration and quality should be tested as an intervention to
      improve glucose control in patients with type 2 diabetes.

PMID- 16983058
TI  - Insomnia, trouble sleeping, and complementary and alternative medicine: Analysis
      of the 2002 national health interview survey data.
AB  - BACKGROUND: Insomnia and other disorders that result in trouble sleeping are
      common in the United States and are often associated with chronic health
      conditions. Some individuals with insomnia or trouble sleeping use complementary
      and alternative medicine (CAM) therapies to treat their condition, but the
      prevalence of such use and the most common types of CAM therapies selected are
      not known. METHODS: Prevalence of insomnia or trouble sleeping and of CAM use for
      treating such conditions was examined using the 2002 National Health Interview
      Survey. Logistic regression was used to examine associations between insomnia or
      trouble sleeping, comorbid conditions, and use of CAM treatments. RESULTS: The 12
      month prevalence rate of insomnia or trouble sleeping was 17.4%. There was a
      strong positive association between adults who reported having insomnia or
      trouble sleeping and adults who reported 4 of 5 common conditions: obesity
      (adjusted odds ratio [OR], 1.15; 99% confidence interval [CI], 1.01-1.31),
      hypertension (OR, 1.32; 99% CI, 1.16-1.51), congestive heart failure (OR, 2.24;
      99% CI, 1.60-3.14), and anxiety or depression (OR, 5.64; 99% CI, 5.07-6.29). Of
      those with insomnia or trouble sleeping, 4.5% used some form of CAM therapy to
      treat their condition. CONCLUSIONS: According to the National Health Interview
      Survey analysis, over 1.6 million civilian, noninstitutionalized adult US
      citizens use CAM to treat insomnia or trouble sleeping. The details of this
      analysis will serve as a guide for future research on CAM therapies for sleep
      disorders.

PMID- 16983059
TI  - Infliximab and human immunodeficiency virus infection: Viral load reduction and
      CD4+ T-cell loss related to apoptosis.

PMID- 16983060
TI  - The role of deranged glucose metabolism.

PMID- 16983061
TI  - Corticosteroids and atrial fibrillation: Risks or benefits?

PMID- 16983062
TI  - Corticosteroids in atrial fibrillation: Friends or foes?

PMID- 16983063
TI  - It is time to stop comparing blood pressure-lowering drugs with placebo.

PMID- 16983064
TI  - Analytic errors undermine conclusions of cardiovascular study.

PMID- 16983065
TI  - Notice of Retraction: "The relation between pulse pressure and cardiovascular
      mortality in 12,763 middle-aged men from various parts of the world: a 25-year
      follow-up of the seven countries study" (Arch Intern Med. 2005;165:2142-2147).

PMID- 16983066
TI  - Profile of Ranulfo Romo.

PMID- 16983067
TI  - Functional CD8+ but not CD4+ T cell responses develop independent of thymic
      epithelial MHC.
AB  - The role of nonthymic epithelial (non-TE) MHC in T cell repertoire selection
      remains controversial. To analyze the relative roles of thymic epithelial (TE)
      and non-TE MHC in T cell repertoire selection, we have generated tetraparental
      aggregation chimeras (B6-nude<=>BALB/c and B6<=>BALB/c-nude) harboring T and B
      cells from both parents, whereas TE cells originated exclusively from the non
      nude donor. These chimeras mounted protective virus-specific TE and non-TE MHC
      restricted T cell responses. To further evaluate whether non-TE MHC alone was
      sufficient to generate a functional T cell repertoire, we generated tetraparental
      aggregation chimeras lacking MHC class II (B6-nude<=>MHCII(-/-)) or both MHC
      molecules (B6-nude<=>MHCI(-/-)II(-/-)) on TE cells, but not on cells of B6-nude
      origin. Chimeras with MHC-deficient TE cells mounted functional virus-specific
      CD8+ but not CD4+ T cell responses. Thus, maturation of functional CD4+ T cell
      responses required MHC class II on thymic epithelium, whereas CD8+ T cells
      matured in the absence of TE MHC.

PMID- 16983068
TI  - K+ channel selectivity depends on kinetic as well as thermodynamic factors.
AB  - Potassium channels are necessary for a number of essential biological tasks such
      as the generation of action potentials and setting the resting membrane potential
      in cells, both of which require that these channels selectively permit the
      passage of potassium ions while suppressing the flow of other ions. Generally,
      this selectivity is attributed to a narrow stretch of the channel known as the
      selectivity filter. Over this stretch ions are dehydrated, and the backbone
      oxygen atoms of the protein mimic the ion's loss of coordination by water.
      However, channels are long pores with spatially distinct ion-binding sites that
      all must be traversed during ion permeation. We have shown that selectivity of
      mutant Kir3.2 (GIRK2) channels can be substantially amplified by introducing
      acidic residues into the cavity, a binding site below the selectivity filter.
      Here, we carry out electrostatic calculations on homology models to quantify the
      degree of stabilization that these mutations have on ions in the cavity. We then
      construct a multiion model of ion permeation to calculate the channel's
      permeability to potassium relative to sodium. This kinetic model uses rates
      derived from the electrostatic calculations and demonstrates that nonselective
      electrostatic stabilization of cations in the cavity can amplify channel
      selectivity independently of the selectivity filter. This nonintuitive result
      highlights the dependence of channel properties on the entire channel
      architecture and suggests that selectivity may not be fully understood by
      focusing solely on thermodynamic considerations of ion dehydration and the
      energetics of the selectivity filter.

PMID- 16983069
TI  - Electrostatic interactions in the channel cavity as an important determinant of
      potassium channel selectivity.
AB  - Potassium channels are membrane proteins that allow the passage of potassium ions
      at near diffusion rates while severely limiting the flux of the slightly smaller
      sodium ions. Although studies thus far have focused on the narrowest part of the
      channel, known as the selectivity filter, channels are long pores with multiple
      ions that traverse the selectivity filter, the water-filled central cavity, and
      the rest of the pore formed by cytoplasmic domains. Here, we present experimental
      analyses on Kir3.2 (GIRK2), a G protein-activated inwardly rectifying potassium
      (Kir) channel, showing that a negative charge introduced at a pore-facing
      position in the cavity (N184) below the selectivity filter restores both K(+)
      selectivity and inward rectification properties to the nonselective S177W mutant
      channel. Molecular modeling demonstrates that the negative residue has no effect
      on the geometry of the selectivity filter, suggesting that it has a local effect
      on the cavity ion. Moreover, restoration of selectivity does not depend on the
      exact location of the charge in the central cavity as long as this residue faces
      the pore, where it is in close contact with permeant ions. Our results indicate
      that interactions between permeant ions and the channel cavity can influence ion
      selectivity and channel block by means of an electrostatic effect.

PMID- 16983070
TI  - The X-linked lymphoproliferative disease gene product SAP associates with PAK
      interacting exchange factor and participates in T cell activation.
AB  - SLAM (signaling lymphocyte activation molecule)-associated protein (SAP) is a Src
      homology 2 (SH2) domain-containing adaptor expressed in T cells and natural
      killer cells. Its essential role in immune responses is underscored by the recent
      finding that mutations in SAP result in a rare but fatal X-linked
      lymphoproliferative disease (XLP). Although SAP is known to associate with SLAM
      family receptors, the exact molecular mechanism by which SAP regulates lymphocyte
      signaling remains elusive. We here report that in T cells, SAP associates with
      the PAK-interacting exchange factor (PIX), a guanine nucleotide exchange factor
      (GEF) specific for Rac/Cdc42 GTPases. Moreover, SAP, PIX, and an activated form
      of Cdc42 form a complex in mammalian cells. We demonstrate that the SAP-PIX
      interaction is specific and is mediated by the C-terminal region of the SAP SH2
      domain and the PIX SH3 domain. We further show that SAP is required for the
      recruitment of PIX to the SLAM-family receptors. Interestingly, overexpression of
      SAP, but not its homolog EAT-2, leads to a synergistic activation of nuclear
      factor of activating T cells (NFAT) in combination with a calcium signal in T
      cells. This SAP-mediated activation appears to be receptor-dependent and can be
      blocked by a dominant negative form of PIX. Taken together, our data strongly
      suggest that, in addition to the known SAP-interacting kinase Fyn, PIX may be
      another key player in SAP-mediated T cell activation.

PMID- 16983071
TI  - Crystal structure of 12-oxophytodienoate reductase 3 from tomato: self-inhibition
      by dimerization.
AB  - 12-Oxophytodienoate reductase (OPR) 3, a homologue of old yellow enzyme (OYE),
      catalyzes the reduction of 9S,13S-12-oxophytodienoate to the corresponding
      cyclopentanone, which is subsequently converted to the plant hormone jasmonic
      acid (JA). JA and JA derivatives, as well as 12-oxophytodienoate and related
      cyclopentenones, are known to regulate gene expression in plant development and
      defense. Together with other oxygenated fatty acid derivatives, they form the
      oxylipin signature in plants, which resembles the pool of prostaglandins in
      animals. Here, we report the crystal structure of OPR3 from tomato and of two
      OPR3 mutants. Although the catalytic residues of OPR3 and related OYEs are highly
      conserved, several characteristic differences can be discerned in the substrate
      binding regions, explaining the remarkable substrate stereoselectivity of OPR
      isozymes. Interestingly, OPR3 crystallized as an extraordinary self-inhibited
      dimer. Mutagenesis studies and biochemical analysis confirmed a weak dimerization
      of OPR3 in vitro, which correlated with a loss of enzymatic activity. Based on
      structural data of OPR3, a putative mechanism for a strong and reversible
      dimerization of OPR3 in vivo that involves phosphorylation of OPR3 is suggested.
      This mechanism could contribute to the shaping of the oxylipin signature, which
      is critical for fine-tuning gene expression in plants.

PMID- 16983072
TI  - Genes with internal repeats require the THO complex for transcription.
AB  - The evolutionarily conserved multisubunit THO complex, which is recruited to
      actively transcribed genes, is required for the efficient expression of FLO11 and
      other yeast genes that have long internal tandem repeats. FLO11 transcription
      elongation in Tho- mutants is hindered in the region of the tandem repeats,
      resulting in a loss of function. Moreover, the repeats become genetically
      unstable in Tho- mutants. A FLO11 gene without the tandem repeats is transcribed
      equally well in Tho+ or Tho- strains. The Tho- defect in transcription is
      suppressed by overexpression of topoisomerase I, suggesting that the THO complex
      functions to rectify aberrant structures that arise during transcription.

PMID- 16983073
TI  - The Arabidopsis thaliana vernalization response requires a polycomb-like protein
      complex that also includes VERNALIZATION INSENSITIVE 3.
AB  - In Arabidopsis thaliana, the promotion of flowering by cold temperatures,
      vernalization, is regulated via a floral-repressive MADS box transcription
      factor, FLOWERING LOCUS C (FLC). Vernalization leads to the epigenetic repression
      of FLC expression, a process that requires the polycomb group (PcG) protein
      VERNALIZATION 2 (VRN2) and the plant homeodomain protein VERNALIZATION
      INSENSITIVE 3 (VIN3). We demonstrate that the repression of FLC by vernalization
      requires homologues of other Polycomb Repressive Complex 2 proteins and VRN2. We
      show in planta that VRN2 and VIN3 are part of a large protein complex that can
      include the PcG proteins FERTILIZATION INDEPENDENT ENDOSPERM, CURLY LEAF, and
      SWINGER. These findings suggest a single protein complex is responsible for
      histone deacetylation at FLC and histone methylation at FLC in vernalized plants.
      The abundance of the complex increases during vernalization and declines after
      plants are returned to higher temperatures, consistent with the complex having a
      role in establishing FLC repression.

PMID- 16983074
TI  - Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models
      and depress molecular motor function.
AB  - Dilated cardiomyopathy (DCM) leads to heart failure, a leading cause of death in
      industrialized nations. Approximately 30% of DCM cases are genetic in origin,
      with some resulting from point mutations in cardiac myosin, the molecular motor
      of the heart. The effects of these mutations on myosin's molecular mechanics have
      not been determined. We have engineered two murine models characterizing the
      physiological, cellular, and molecular effects of DCM-causing missense mutations
      (S532P and F764L) in the alpha-cardiac myosin heavy chain and compared them with
      WT mice. Mutant mice developed morphological and functional characteristics of
      DCM consistent with the human phenotypes. Contractile function of isolated
      myocytes was depressed and preceded left ventricular dilation and reduced
      fractional shortening. In an in vitro motility assay, both mutant cardiac myosins
      exhibited a reduced ability to translocate actin (V(actin)) but had similar force
      generating capacities. Actin-activated ATPase activities were also reduced.
      Single-molecule laser trap experiments revealed that the lower V(actin) in the
      S532P mutant was due to a reduced ability of the motor to generate a step
      displacement and an alteration of the kinetics of its chemomechanical cycle.
      These results suggest that the depressed molecular function in cardiac myosin may
      initiate the events that cause the heart to remodel and become pathologically
      dilated.

PMID- 16983075
TI  - Determining the underlying Fermi surface of strongly correlated superconductors.
AB  - The notion of a Fermi surface (FS) is one of the most ingenious concepts
      developed by solid-state physicists during the past century. It plays a central
      role in our understanding of interacting electron systems. Extraordinary efforts
      have been undertaken, by both experiment and theory, to reveal the FS of the high
      temperature superconductors, the most prominent class of strongly correlated
      superconductors. Here, we discuss some of the prevalent methods used to determine
      the FS and show that they generally lead to erroneous results close to half
      filling and at low temperatures, because of the large superconducting gap
      (pseudogap) below (above) the superconducting transition temperature. Our
      findings provide a perspective on the interplay between strong correlations and
      superconductivity and highlight the importance of strong coupling theories for
      the characterization and determination of the underlying FS in angle-resolved
      photoemission spectroscopy experiments.

PMID- 16983077
TI  - Helmholtz decomposition coupling rotational to irrotational flow of a viscous
      fluid.
AB  - In this work, I present the form of the Navier-Stokes equations implied by the
      Helmholtz decomposition in which the relation of the irrotational and rotational
      velocity fields is made explicit. The idea of self-equilibration of irrotational
      viscous stresses is introduced. The decomposition is constructed by first
      selecting the irrotational flow compatible with the flow boundaries and other
      prescribed conditions. The rotational component of velocity is then the
      difference between the solution of the Navier-Stokes equations and the selected
      irrotational flow. To satisfy the boundary conditions, the irrotational field is
      required, and it depends on the viscosity. Five unknown fields are determined by
      the decomposed form of the Navier-Stokes equations for an incompressible fluid:
      the rotational component of velocity, the pressure, and the harmonic potential.
      These five fields may be readily identified in analytic solutions available in
      the literature. It is clear from these exact solutions that potential flow of a
      viscous fluid is required to satisfy prescribed conditions, like the no-slip
      condition at the boundary of a solid or continuity conditions across a two-fluid
      boundary. It can be said that equations governing the Helmholtz decomposition
      describe the modification of irrotational flow due to vorticity, but the analysis
      shows the two fields are coupled and cannot be completely determined
      independently.

PMID- 16983076
TI  - TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the
      early phase of diet-induced obesity.
AB  - The vgf gene has been identified as an energy homeostasis regulator. Vgf encodes
      a 617-aa precursor protein that is processed to yield an incompletely
      characterized panel of neuropeptides. Until now, it was an unproved assumption
      that VGF-derived peptides could regulate metabolism. Here, a VGF peptide
      designated TLQP-21 was identified in rat brain extracts by means of
      immunoprecipitation, microcapillary liquid chromatography-tandem MS, and database
      searching algorithms. Chronic intracerebroventricular (i.c.v.) injection of TLQP
      21 (15 mug/day for 14 days) increased resting energy expenditure (EE) and rectal
      temperature in mice. These effects were paralleled by increased epinephrine and
      up-regulation of brown adipose tissue beta2-AR (beta2 adrenergic receptor) and
      white adipose tissue (WAT) PPAR-delta (peroxisome proliferator-activated receptor
      delta), beta3-AR, and UCP1 (uncoupling protein 1) mRNAs and were independent of
      locomotor activity and thyroid hormones. Hypothalamic gene expression of
      orexigenic and anorexigenic neuropeptides was unchanged. Furthermore, in mice
      that were fed a high-fat diet for 14 days, TLQP-21 prevented the increase in body
      and WAT weight as well as hormonal changes that are associated with a high-fat
      regimen. Biochemical and molecular analyses suggest that TLQP-21 exerts its
      effects by stimulating autonomic activation of adrenal medulla and adipose
      tissues. In conclusion, we present here the identification in the CNS of a
      previously uncharacterized VGF-derived peptide and prove that its chronic i.c.v.
      infusion effected an increase in EE and limited the early phase of diet-induced
      obesity.

PMID- 16983078
TI  - Vibrio cholerae virulence regulator-coordinated evasion of host immunity.
AB  - To successfully propagate and cause disease, pathogenic bacteria must modulate
      their transcriptional activities in response to pressures exerted by the host
      immune system, including secreted immunoglobulins such as secretory IgA (S-IgA),
      which can bind and agglutinate bacteria. Here, we present a previously
      undescribed flow cytometry-based screening method to identify bacterial genes
      expressed in vitro and repressed during infections of Vibrio cholerae, an aquatic
      Gram-negative bacterium responsible for the severe diarrheal disease cholera. We
      identified a type IV mannose-sensitive hemagglutinin (MSHA) pilus that is
      repressed specifically in vivo. We showed that bacteria that failed to turn off
      MSHA biosynthesis were unable to colonize the intestines of infant mice in the
      presence of S-IgA. We also found that V. cholerae bound S-IgA in an MSHA
      dependent and mannose-sensitive fashion and that binding of S-IgA prevented
      bacteria from penetrating mucus barriers and attaching to the surface of
      epithelial cells. The ability of V. cholerae to evade the non-antigen-specific
      binding of S-IgA by down-regulating a surface adhesin represents a previously
      undescribed mechanism of immune evasion in pathogenic bacteria. In addition, we
      found that repression of MSHA was mediated by the key virulence transcription
      factor ToxT, indicating that V. cholerae is able to coordinate both virulence
      gene activation and repression to evade host defenses and successfully colonize
      intestines.

PMID- 16983079
TI  - Epistasis correlates to genomic complexity.
AB  - Whether systematic genetic interactions (epistasis) occur at the genomic scale
      remains a challenging topic in evolutionary biology. Epistasis should make a
      significant contribution to variation in complex traits and influence the
      evolution of genetic systems as sex, diploidy, dominance, or the contamination of
      genomes with deleterious mutations. We have collected data from widely different
      organisms and quantified epistasis in a common, per-generation scale. Simpler
      genomes, such as those of RNA viruses, display antagonistic epistasis (mutations
      have smaller effects together than expected); bacterial microorganisms do not
      apparently deviate from independent effects, whereas in multicellular eukaryotes,
      a transition toward synergistic epistasis occurs (mutations have larger effects
      together than expected). We propose that antagonistic epistasis might be a
      property of compact genomes with few nonpleiotropic biological functions, whereas
      in complex genomes, synergism might emerge from mutational robustness.

PMID- 16983080
TI  - Ex vivo pretreatment of bone marrow mononuclear cells with endothelial NO
      synthase enhancer AVE9488 enhances their functional activity for cell therapy.
AB  - Bone marrow mononuclear cells (BMC) from patients with ischemic cardiomyopathy
      (ICMP) show a reduced neovascularization capacity in vivo. NO plays an important
      role in neovascularization, and NO bioavailability is typically reduced in
      patients with ICMP. We investigated whether the impaired neovascularization
      capacity of ICMP patient-derived progenitor cells can be restored by pretreatment
      with the novel endothelial NO synthase (eNOS) transcription enhancer AVE9488
      (AVE). Ex vivo pretreatment of BMC from patients with ICMP with AVE significantly
      increased eNOS mRNA expression by 2.1-fold (P < 0.05) and eNOS activity as
      assessed by ESR by >3-fold (P < 0.05). The increased eNOS expression was
      associated with an enhanced migratory capacity in vitro (P < 0.01) and improved
      neovascularization capacity of the infused BMC in an ischemic hind limb model in
      vivo (P < 0.001). The improvement in ischemic limb perfusion after infusion of
      AVE-pretreated BMC resulted in an increase in swimming time (P < 0.05). The
      enhancement of limb perfusion by AVE-treated BMC was abrogated by ex vivo
      pretreatment with the eNOS inhibitor N(G)-nitro-l-arginine methyl ester.
      Consistently, AVE showed no effect on the impaired migratory capacity of BMC
      derived from eNOS-deficient mice, documenting the specific involvement of NO. The
      reduced neovascularization capacity of BMC from patients with ICMP may limit
      their therapeutic potential in cell therapy studies. Here, we show that
      pharmacological enhancement of eNOS expression with AVE at least partially
      reverses the impaired functional activity of BMC from ICMP patients, highlighting
      the critical role of NO for progenitor cell function.

PMID- 16983081
TI  - The cellular basis for parallel neural transmission of a high-frequency stimulus
      and its low-frequency envelope.
AB  - Sensory stimuli often have rich temporal and spatial structure. One class of
      stimuli that are common to visual and auditory systems and, as we show, the
      electrosensory system are signals that contain power in a narrow range of
      temporal (or spatial) frequencies. Characteristic of this class of signals is a
      slower variation in their amplitude, otherwise known as an envelope. There is
      evidence suggesting that, in the visual cortex, both narrowband stimuli and their
      envelopes are coded for in separate and parallel streams. The implementation of
      this parallel transmission is not well understood at the cellular level. We have
      identified the cellular basis for the parallel transmission of signal and
      envelope in the electrosensory system: a two-cell network consisting of an
      interneuron connected to a pyramidal cell by means of a slow synapse. This
      circuit could, in principle, be implemented in the auditory or visual cortex by
      the previously identified biophysics of cortical interneurons.

PMID- 16983082
TI  - Inhibitors of Plasmodium falciparum methionine aminopeptidase 1b possess
      antimalarial activity.
AB  - With >1 million deaths annually, mostly among children in sub-Saharan Africa,
      malaria poses one of the most critical challenges in medicine today. Although
      introduction of the artemisinin class of antimalarial drugs has offered a
      temporary solution to the problem of drug resistance, new antimalarial drugs are
      needed to ensure effective control of the disease in the future. Herein, we have
      investigated members of the methionine aminopeptidase family as potential
      antimalarial targets. The Plasmodium falciparum methionine aminopeptidase 1b
      (PfMetAP1b), one of four MetAP proteins encoded in the P. falciparum genome, was
      cloned, overexpressed, purified, and used to screen a 175,000-compound library
      for inhibitors. A family of structurally related inhibitors containing a 2-(2
      pyridinyl)-pyrimidine core was identified. Structure/activity studies led to the
      identification of a potent PfMetAP1b inhibitor, XC11, with an IC(50) of 112 nM.
      XC11 was highly selective for PfMetAP1b and did not exhibit significant
      cytotoxicity against primary human fibroblasts. Most importantly, XC11 inhibited
      the proliferation of P. falciparum strains 3D7 [chloroquine (CQ)-sensitive] and
      Dd2 (multidrug-resistant) in vitro and is active in mouse malaria models for both
      CQ-sensitive and CQ-resistant strains. These results suggest that PfMetAP1b is a
      promising target and XC11 is an important lead compound for the development of
      novel antimalarial drugs.

PMID- 16983083
TI  - Hydroxymalonyl-acyl carrier protein (ACP) and aminomalonyl-ACP are two additional
      type I polyketide synthase extender units.
AB  - Combinatorial biosynthesis of type I polyketide synthases is a promising approach
      for the generation of new structural derivatives of polyketide-containing natural
      products. A target of this approach has been to change the extender units
      incorporated into a polyketide backbone to alter the structure and activity of
      the natural product. One limitation to these efforts is that only four extender
      units were known: malonyl-CoA, methylmalonyl-CoA, ethylmalonyl-CoA, and
      methoxymalonyl-acyl carrier protein (ACP). The chemical attributes of these
      extender units are quite similar, with the exception of the potential hydrogen
      bonding interactions by the oxygen of the methoxy moiety. Furthermore, the
      incorporated extender units are not easily modified by using simple chemical
      approaches when combinatorial biosynthesis is coupled to semisynthetic chemistry.
      We recently proposed the existence of two additional extender units,
      hydroxymalonyl-ACP and aminomalonyl-ACP, involved in the biosynthesis of
      zwittermicin A. These extender units offer unique possibilities for combinatorial
      biosynthesis and semisynthetic chemistry because of the introduction of free
      hydroxyl and amino moieties into a polyketide structure. Here, we present the
      biochemical and mass spectral evidence for the formation of these extender units.
      This evidence shows the formation of ACP-linked extender units for polyketide
      synthesis. Interestingly, aminomalonyl-ACP formation involves enzymology
      typically found in nonribosomal peptide synthesis.

PMID- 16983084
TI  - Differences in vertebrate microRNA expression.
AB  - MicroRNAs (miRNAs) attenuate gene expression by means of translational inhibition
      and mRNA degradation. They are abundant, highly conserved, and predicted to
      regulate a large number of transcripts. Several hundred miRNA classes are known,
      and many are associated with cell proliferation and differentiation. Many exhibit
      tissue-specific expression, which aids in evaluating their functions, and it has
      been assumed that their high level of sequence conservation implies a high level
      of expression conservation. A limited amount of data supports this, although
      discrepancies do exist. By comparing the expression of approximately 100 miRNAs
      in medaka and chicken with existing data for zebrafish and mouse, we conclude
      that the timing and location of miRNA expression is not strictly conserved. In
      some instances, differences in expression are associated with changes in miRNA
      copy number, genomic context, or both between species. Variation in miRNA
      expression is more pronounced the greater the differences in physiology, and it
      is enticing to speculate that changes in miRNA expression may play a role in
      shaping the physiological differences produced during animal development.

PMID- 16983085
TI  - A variable immunoreceptor in a subpopulation of human neutrophils.
AB  - Neutrophils are thought to rely solely on nonspecific immune mechanisms. Here we
      provide molecular biological, immunological, ultrastructural, and functional
      evidence for the presence of a T cell receptor (TCR)-based variable
      immunoreceptor in a 5-8% subpopulation of human neutrophils. We demonstrate that
      these peripheral blood neutrophils express variable and individual-specific
      TCRalphabeta repertoires and the RAG1/RAG2 recombinase complex. The
      proinflammatory cytokine granulocyte colony-stimulating factor regulates
      expression of the neutrophil immunoreceptor and RAG1/RAG2 in vivo. Specific
      engagement of the neutrophil TCR complex protects from apoptosis and stimulates
      secretion of the neutrophil-activating chemokine IL-8. Our results, which also
      demonstrate the presence of the TCR in murine neutrophils, suggest the
      coexistence of a variable and an innate host defense system in mammalian
      neutrophils.

PMID- 16983086
TI  - An alpha2-macroglobulin-like protein is the cue to gregarious settlement of the
      barnacle Balanus amphitrite.
AB  - Many benthic marine invertebrates, like barnacles, have a planktonic larval stage
      whose primary purpose is dispersal. How these species colonize suitable substrata
      is fundamental to understanding their evolution, population biology, and wider
      community dynamics. Unlike larval dispersal, settlement occurs on a relatively
      small spatial scale and involves larval behavior in response to physical and
      chemical characteristics of the substratum. Biogenic chemical cues have been
      implicated in this process. Their identification, however, has proven
      challenging, no more so than for the chemical basis of barnacle gregariousness,
      which was first described >50 years ago. We now report that a biological cue to
      gregarious settlement, the settlement-inducing protein complex (SIPC), of the
      major fouling barnacle Balanus amphitrite is a previously undescribed
      glycoprotein. The SIPC shares a 30% sequence homology with the thioester
      containing family of proteins that includes the alpha(2)-macroglobulins. The cDNA
      (5.2 kb) of the SIPC encodes a protein precursor comprising 1,547 aa with a 17
      residue signal peptide region. A number of structural characteristics and the
      absence of a thioester bond in the SIPC suggest that this molecule is a
      previously undescribed protein that may have evolved by duplication from an
      ancestral alpha(2)-macroglobulin gene. Although the SIPC is regarded as an adult
      cue that is recognized by the cyprid at settlement, it is also expressed in the
      juvenile and in larvae, where it may function in larva-larva settlement
      interactions.

PMID- 16983087
TI  - Gata4 is required for maintenance of postnatal cardiac function and protection
      from pressure overload-induced heart failure.
AB  - An important event in the pathogenesis of heart failure is the development of
      pathological cardiac hypertrophy. In cultured cardiomyocytes, the transcription
      factor Gata4 is required for agonist-induced hypertrophy. We hypothesized that,
      in the intact organism, Gata4 is an important regulator of postnatal heart
      function and of the hypertrophic response of the heart to pathological stress. To
      test this hypothesis, we studied mice heterozygous for deletion of the second
      exon of Gata4 (G4D). At baseline, G4D mice had mild systolic and diastolic
      dysfunction associated with reduced heart weight and decreased cardiomyocyte
      number. After transverse aortic constriction (TAC), G4D mice developed overt
      heart failure and eccentric cardiac hypertrophy, associated with significantly
      increased fibrosis and cardiomyocyte apoptosis. Inhibition of apoptosis by
      overexpression of the insulin-like growth factor 1 receptor prevented TAC-induced
      heart failure in G4D mice. Unlike WT-TAC controls, G4D-TAC cardiomyocytes
      hypertrophied by increasing in length more than width. Gene expression profiling
      revealed up-regulation of genes associated with apoptosis and fibrosis, including
      members of the TGF-beta pathway. Our data demonstrate that Gata4 is essential for
      cardiac function in the postnatal heart. After pressure overload, Gata4 regulates
      the pattern of cardiomyocyte hypertrophy and protects the heart from load-induced
      failure.

PMID- 16983088
TI  - Sex-biased maternal effects reduce ectoparasite-induced mortality in a passerine
      bird.
AB  - Duration of developmental stages in animals evolves under contrasting selection
      pressures of age-specific mortality and growth requirements. When relative
      importance of these effects varies across environments, evolution of
      developmental periods is expected to be slow. In birds, maternal effects on egg
      laying order and offspring growth, two proximate determinants of nestling period,
      should enable rapid adjustment of developmental periods to even widely
      fluctuating mortality rates. We test this hypothesis in a population of house
      finches (Carpodacus mexicanus) breeding under two contrasting mortality risks:
      (i) a nest mite-free condition when selection on offspring survival favors a
      longer time in the nest; and (ii) a mite infestation when selection favors a
      shorter nest tenure. Mites affected survival of sons more than daughters, and
      females breeding under mite infestation laid male eggs last and female eggs first
      in the clutch, thereby reducing sons' exposure to mites and associated mortality.
      Strong sex bias in laying order and growth patterns enabled mite-infested
      offspring to achieve similar fledging size, despite a shorter nest tenure,
      compared with mite-free conditions. In mite-infested nests, male nestlings
      hatched at larger sizes, completed growth earlier, and had faster initial growth
      compared with mite-free nests, whereas mite-infested females grew more slowly but
      for a longer period of time. A combination of heavily sex-biased laying order and
      sex differences in growth patterns lowered mite-induced mortality by >10% in both
      sexes. Thus, strong maternal effects can account for frequently observed, but
      theoretically unexpected, concordance of mortality risks and growth patterns,
      especially under fluctuating ecological conditions.

PMID- 16983089
TI  - Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3
      cleavage plays an essential role in cardiac myocyte apoptosis.
AB  - Rho-associated coiled-coil protein kinase 1 (ROCK-1) is a direct cleavage
      substrate of activated caspase-3, which is associated with heart failure. In the
      course of human heart failure, we found marked cleavage of ROCK-1 resulting in a
      130-kDa subspecies, which was absent in normal hearts and in an equivalent cohort
      of patients with left ventricular assist devices. Murine cardiomyocytes treated
      with doxorubicin led to enhanced ROCK-1 cleavage and apoptosis, all of which was
      blocked by a caspase-3 inhibitor. In addition, a bitransgenic mouse model of
      severe cardiomyopathy, which overexpresses Gq protein and hematopoietic
      progenitor kinase-/germinal center kinase-like kinase, revealed the robust
      accumulation of the 130-kDa ROCK-1 cleaved fragment. This constitutively active
      ROCK-1 subspecies, when expressed in cardiomyocytes, led to caspase-3 activation,
      indicating a positive feed-forward regulatory loop. ROCK-1-dependent caspase-3
      activation was coupled with the activation of PTEN and the subsequent inhibition
      of protein kinase B (Akt) activity, all of which was attenuated by siRNA directed
      against ROCK-1 expression. Similarly, ROCK-1-null mice (Rock-1(-/-)) showed a
      marked reduction in myocyte apoptosis associated with pressure overload. These
      data suggest an obligatory role for ROCK-1 cleavage in promoting apoptotic
      signals in myocardial hypertrophy and/or failure.

PMID- 16983090
TI  - Autophagy-mediated reentry of Francisella tularensis into the endocytic
      compartment after cytoplasmic replication.
AB  - Intracellular bacterial pathogens evade the bactericidal functions of mammalian
      cells by physical escape from their phagosome and replication into the cytoplasm
      or through the modulation of phagosome maturation and biogenesis of a membrane
      bound replicative organelle. Here, we detail in murine primary macrophages the
      intracellular life cycle of Francisella tularensis, a highly infectious bacterium
      that survives and replicates within mammalian cells. After transient interactions
      with the endocytic pathway, bacteria escaped from their phagosome by 1 h after
      infection and underwent replication in the cytoplasm from 4 to 20 h after
      infection. Unexpectedly, the majority of bacteria were subsequently found to be
      enclosed within large, juxtanuclear, LAMP-1-positive vacuoles called Francisella
      containing vacuoles (FCVs). FCV formation required intracytoplasmic replication
      of bacteria. Using electron and fluorescence microscopy, we observed that the
      FCVs contained morphologically intact bacteria, despite fusing with lysosomes.
      FCVs are multimembranous structures that accumulate monodansylcadaverine and
      display the autophagy-specific protein LC3 on their membrane. Formation of FCVs
      was significantly inhibited by 3-methyladenine, confirming a role for the
      autophagic pathway in the biogenesis of these organelles. Taken together, our
      results demonstrate that, via autophagy, F. tularensis reenters the endocytic
      pathway after cytoplasmic replication, a process thus far undescribed for
      intracellular pathogens.

PMID- 16983091
TI  - Structural insights into methyltransfer reactions of a corrinoid iron-sulfur
      protein involved in acetyl-CoA synthesis.
AB  - The cobalt- and iron-containing corrinoid iron-sulfur protein (CoFeSP) is
      functional in the acetyl-CoA (Ljungdahl-Wood) pathway of autotrophic carbon
      fixation in various bacteria and archaea, where it is essential for the
      biosynthesis of acetyl-CoA. CoFeSP acts in two methylation reactions: the
      transfer of a methyl group from methyltransferase (MeTr)-bound
      methyltetrahydrofolate to the cob(I)amide of CoFeSP and the transfer of the
      methyl group of methyl-cob(III)amide to the reduced Ni-Ni-[4Fe-4S] active site
      cluster A of acetyl-CoA synthase (ACS). We have solved the crystal structure of
      as-isolated CoFeSP(Ch) from the CO-oxidizing hydrogenogenic bacterium
      Carboxydothermus hydrogenoformans at 1.9-A resolution. The heterodimeric protein
      consists of two tightly interacting subunits with pseudo-twofold symmetry. The
      large CfsA subunit comprises three domains, of which the N-terminal domain binds
      the [4Fe-4S] cluster, the middle domain is a (betaalpha)(8)-barrel, and the C
      terminal domain shows an open fold and binds Cobeta-aqua-(5,6
      dimethylbenzimidazolylcobamide) in a "base-off" state without a protein ligand at
      the cobalt ion. The small CfsB subunit also displays a (betaalpha)(8)-barrel fold
      and interacts with the upper side of the corrin macrocycle. Structure-based
      alignments show that both (betaalpha)(8)-barrel domains are related to the MeTr
      in the acetyl-CoA pathway and to the folate domain of methionine synthase. We
      suggest that the C-terminal domain of the large subunit is the mobile element
      that allows the necessary interaction of CoFeSP(Ch) with the active site of
      ACS(Ch) and the methyltetrahydrofolate carrying MeTr. The conformation in the
      crystal structure shields the two open coordinations of cobalt and likely
      represents a resting state.

PMID- 16983092
TI  - Task-modulated "what" and "where" pathways in human auditory cortex.
AB  - Human neuroimaging studies suggest that localization and identification of
      relevant auditory objects are accomplished via parallel parietal-to-lateral
      prefrontal "where" and anterior-temporal-to-inferior-frontal "what" pathways,
      respectively. Using combined hemodynamic (functional MRI) and electromagnetic
      (magnetoencephalography) measurements, we investigated whether such dual pathways
      exist already in the human nonprimary auditory cortex, as suggested by animal
      models, and whether selective attention facilitates sound localization and
      identification by modulating these pathways in a feature-specific fashion. We
      found a double dissociation in response adaptation to sound pairs with phonetic
      vs. spatial sound changes, demonstrating that the human nonprimary auditory
      cortex indeed processes speech-sound identity and location in parallel anterior
      "what" (in anterolateral Heschl's gyrus, anterior superior temporal gyrus, and
      posterior planum polare) and posterior "where" (in planum temporale and posterior
      superior temporal gyrus) pathways as early as approximately 70-150 ms from
      stimulus onset. Our data further show that the "where" pathway is activated
      approximately 30 ms earlier than the "what" pathway, possibly enabling the brain
      to use top-down spatial information in auditory object perception. Notably,
      selectively attending to phonetic content modulated response adaptation in the
      "what" pathway, whereas attending to sound location produced analogous effects in
      the "where" pathway. This finding suggests that selective-attention effects are
      feature-specific in the human nonprimary auditory cortex and that they arise from
      enhanced tuning of receptive fields of task-relevant neuronal populations.

PMID- 16983093
TI  - Ralstonia solanacearum requires F-box-like domain-containing type III effectors
      to promote disease on several host plants.
AB  - The phytopathogenic bacterium Ralstonia solanacearum encodes a family of seven
      type III secretion system (T3SS) effectors that contain both a leucine-rich
      repeat and an F-box domain. This structure is reminiscent of a class of typical
      eukaryotic proteins called F-box proteins. The latter, together with Skp1 and
      Cullin1 subunits, constitute the SCF-type E3 ubiquitin ligase complex and control
      specific protein ubiquitinylation. In the eukaryotic cell, depending on the
      nature of the polyubiquitin chain, the ubiquitin-tagged proteins either see their
      properties modified or are doomed for degradation by the 26S proteasome. This
      pathway is essential to many developmental processes in plants, ranging from
      hormone signaling and flower development to stress responses. Here, we show that
      these previously undescribed T3SS effectors are putative bacterial F-box proteins
      capable of interacting with a subset of the 19 different Arabidopsis Skp1-like
      proteins like bona fide Arabidopsis F-box proteins. A R. solanacearum strain in
      which all of the seven GALA effector genes have been deleted or mutated was no
      longer pathogenic on Arabidopsis and less virulent on tomato. Furthermore, we
      found that GALA7 is a host-specificity factor, required for disease on Medicago
      truncatula plants. Our results indicate that the GALA T3SS effectors are
      essential to R. solanacearum to control disease. Because the F-box domain is
      essential to the virulence function of GALA7, we hypothesize that these effectors
      act by hijacking their host SCF-type E3 ubiquitin ligases to interfere with their
      host ubiquitin/proteasome pathway to promote disease.

PMID- 16983094
TI  - The von Hippel-Lindau tumor suppressor gene product represses oncogenic beta
      catenin signaling in renal carcinoma cells.
AB  - Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial
      and most sporadic clear cell renal cell carcinoma (RCC), resulting in the
      aberrant expression of genes that control cell proliferation, invasion, and
      angiogenesis. The molecular mechanisms by which VHL loss leads to tumorigenesis
      are not yet fully defined. VHL loss has been shown to allow robust RCC cell
      motility, invasiveness, and morphogenesis in response to hepatocyte growth factor
      (HGF) stimulation, processes that are known to contribute to tumor invasiveness
      and metastatic potential. Among the most likely intracellular mediators of these
      HGF-driven activities is beta-catenin, a structural link between cadherens and
      the actin cytoskeleton, as well as a gene transactivator. We show that
      reconstitution of VHL expression in RCC cells repressed HGF-stimulated beta
      catenin tyrosyl phosphorylation, adherens junction disruption, cytoplasmic beta
      catenin accumulation, and reporter gene transactivation in RCC cells. Ectopic
      expression of a ubiquitination-resistant beta-catenin mutant specifically
      restored HGF-stimulated invasion and morphogenesis in VHL-transfected RCC cells.
      VHL gene silencing in non-RCC renal epithelial cells phenotypically mimicked VHL
      loss in RCC, and HGF-driven invasiveness was blocked by the expression of a
      dominant-negative mutant of Tcf. We conclude that, unlike many other cancers,
      where HGF pathway activation contributes to malignancy through the acquisition of
      autocrine signaling, receptor overexpression, or mutation, in RCC cells VHL loss
      enables HGF-driven oncogenic beta-catenin signaling. These findings identify beta
      catenin as a potential target in biomarker and drug development for RCC.

PMID- 16983095
TI  - Synergistic inhibition of growth of lung carcinomas by antagonists of growth
      hormone-releasing hormone in combination with docetaxel.
AB  - We investigated the effect of antagonists of growth hormone-releasing hormone
      (GHRH) MZ-J-7-138 and JV-1-92 on H460 human non-small cell lung carcinoma (NSCLC)
      xenografted orthotopically into nude mice. Treatment with MZ-J-7-138 or JV-1-92
      inhibited orthotopic growth of H460 NSCLC by 52-65% (P < 0.001) and was
      associated with a significant decrease in protein expression of K-Ras,
      cyclooxygenase-2 (Cox-2) and phospho-Akt (pAkt). In other experiments, treatment
      with MZ-J-7-138 or docetaxel reduced tumor volume of s.c. xenografted H460 human
      NSCLC by 30-36% (P < 0.01). The combination of MZ-J-7-138 and docetaxel resulted
      in a synergistic growth inhibition of H460 NSCLC xenografts of 63%. MZ-J-7-138
      alone or in combination with docetaxel significantly reduced protein levels of K
      Ras, Cox-2, and pAkt by 56-63%. Docetaxel given singly diminished the protein
      levels only of Cox-2 and did not affect K-Ras and pAkt. High-affinity binding
      sites, mRNA, and protein expression of pituitary GHRH receptors and its splice
      variant (SV) 1 were found in H460. H460 NSCLC cells contained GHRH peptide, and
      its growth was significantly inhibited in vitro by 10 microM MZ-J-7-138 (P <
      0.001). Serum insulin-like growth factor 1 (IGF1) was not reduced by either GHRH
      antagonists. These findings suggest that antiproliferative effects of GHRH
      antagonists in H460 NSCLC are associated with down-regulation of K-Ras, Cox-2,
      and pAkt. In conclusion, GHRH antagonists in combination with docetaxel
      synergistically inhibit growth of H460 NSCLC and the expression of K-ras, Cox-2,
      and pAkt, which might abrogate the signal transduction pathways for cell growth
      stimulation and therapeutic resistance.

PMID- 16983096
TI  - Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma
      associated herpesvirus LANA.
AB  - The Kaposi's sarcoma-associated herpesvirus LANA protein is expressed in all
      Kaposi's sarcoma-associated herpesvirus-infected cells, including the tumor cells
      of endemic and AIDS-associated Kaposi sarcoma, primary effusion lymphoma, and
      Castleman disease. LANA modulates cell gene expression, but the mechanisms of
      LANA-mediated transcriptional reprogramming are poorly understood. LANA-repressed
      cell genes were identified by using retroviral-transduced telomerase-immortalized
      microvascular endothelial cells. Transciptional repression of targeted genes was
      relieved by treatment with the methyltransferase inhibitor 5-aza-2'
      deoxycytidine, suggesting a role for DNA methylation in repression. We found that
      LANA coprecipitated with DNA methyltransferases (Dnmts) and recruited endogenous
      DNA methyltransferase activity from the cell extract. LANA preferentially
      relocalized Dnmt3a from the nuclear matrix into the chromatin fraction. Further,
      LANA associated with repressed cellular promoters, recruited Dnmt3a to DNA, and
      facilitated de novo promoter methylation of a down-regulated gene, cadherin 13 (H
      cadherin). The data provide an example of promoter-specific epigenetic DNA
      modification through viral protein recruitment of de novo Dnmt activity.

PMID- 16983097
TI  - An intracellular lamellar-nonlamellar phase transition rationalizes the superior
      performance of some cationic lipid transfection agents.
AB  - Two cationic phospholipid derivatives with asymmetric hydrocarbon chains were
      synthesized: ethyl esters of oleoyldecanoyl-ethylphosphatidylcholine (C18:1/C10
      EPC) and stearoyldecanoyl-ethylphosphatidylcholine (C18:0/C10-EPC). The former
      was 50 times more effective as a DNA transfection agent (human umbilical artery
      endothelial cells) than the latter, despite their similar chemical structure and
      virtually identical lipoplex organization. A likely reason for the superior
      effectiveness of C18:1/C10-EPC relative to C18:0/C10-EPC (and to many other
      cationic lipoids) was suggested by the phases that evolved when these lipoids
      were mixed with negatively charged membrane lipid formulations. The saturated
      C18:0/C10-EPC remained lamellar in mixtures with biomembrane-mimicking lipid
      formulations [e.g., dioleoyl-phosphatidylcholine/dioleoyl
      phosphatidylethanolamine/dioleoyl-phosphatidylserine/cholesterol at 45:20:20:15
      (wt/wt)]; in contrast, the unsaturated C18:1/C10-EPC exhibited a lamellar
      nonlamellar phase transition in such mixtures, which took place at physiological
      temperatures, approximately 37 degrees C. As is well known, lipid vehicles
      exhibit maximum leakiness and contents release in the vicinity of phase
      transitions, especially those involving nonlamellar phase formation. Moreover,
      nonlamellar phase-forming compositions are frequently highly fusogenic. Indeed,
      FRET experiments showed that C18:1/C10-EPC exhibits lipid mixing with negatively
      charged membranes that is several times more extensive than that of C18:0/C10
      EPC. Thus, C18:1/C10-EPC lipoplexes are likely to easily fuse with membranes,
      and, as a result of lipid mixing, the resultant aggregates should exhibit
      extensive phase coexistence and heterogeneity, thereby facilitating DNA release
      and leading to superior transfection efficiency. These results highlight the
      phase properties of the carrier lipid/cellular lipid mixtures as a decisive
      factor for transfection success and suggest a strategy for the rational design of
      superior cationic lipid carriers.

PMID- 16983098
TI  - Regulation of gene expression in the mammalian eye and its relevance to eye
      disease.
AB  - We used expression quantitative trait locus mapping in the laboratory rat (Rattus
      norvegicus) to gain a broad perspective of gene regulation in the mammalian eye
      and to identify genetic variation relevant to human eye disease. Of >31,000 gene
      probes represented on an Affymetrix expression microarray, 18,976 exhibited
      sufficient signal for reliable analysis and at least 2-fold variation in
      expression among 120 F(2) rats generated from an SR/JrHsd x SHRSP intercross.
      Genome-wide linkage analysis with 399 genetic markers revealed significant
      linkage with at least one marker for 1,300 probes (alpha = 0.001; estimated
      empirical false discovery rate = 2%). Both contiguous and noncontiguous loci were
      found to be important in regulating mammalian eye gene expression. We
      investigated one locus of each type in greater detail and identified putative
      transcription-altering variations in both cases. We found an inserted cREL
      binding sequence in the 5' flanking sequence of the Abca4 gene associated with an
      increased expression level of that gene, and we found a mutation of the gene
      encoding thyroid hormone receptor beta2 associated with a decreased expression
      level of the gene encoding short-wavelength sensitive opsin (Opn1sw). In addition
      to these positional studies, we performed a pairwise analysis of gene expression
      to identify genes that are regulated in a coordinated manner and used this
      approach to validate two previously undescribed genes involved in the human
      disease Bardet-Biedl syndrome. These data and analytical approaches can be used
      to facilitate the discovery of additional genes and regulatory elements involved
      in human eye disease.

PMID- 16983099
TI  - Combinations of biomarkers predictive of later life mortality.
AB  - A wide range of biomarkers, reflecting activity in a number of biological systems
      (e.g., neuroendocrine, immune, cardiovascular, and metabolic), have been found to
      prospectively predict disability, morbidity, and mortality outcomes in older
      adult populations. Levels of these biomarkers, singly or in combination, may
      serve as an early warning system of risk for future adverse health outcomes. In
      the current investigation, 13 biomarkers were examined as predictors of mortality
      occurrence over a 12-year period in a sample of men and women (n = 1,189) 70-79
      years of age at enrollment into the study. Biomarkers examined in analyses
      included markers of neuroendocrine functioning (epinephrine, norepinephrine,
      cortisol, and dehydroepiandrosterone), immune activity (C-reactive protein,
      fibrinogen, IL-6, and albumin), cardiovascular functioning (systolic and
      diastolic blood pressure), and metabolic activity [high-density lipoprotein (HDL)
      cholesterol, total to HDL cholesterol ratio, and glycosylated hemoglobin].
      Recursive partitioning techniques were used to identify a set of pathways,
      composed of combinations of different biomarkers, that were associated with a
      high-risk of mortality over the 12-year period. Of the 13 biomarkers examined,
      almost all entered into one or more high-risk pathways although combinations of
      neuroendocrine and immune markers appeared frequently in high-risk male pathways,
      and systolic blood pressure was present in combination with other biomarkers in
      all high-risk female pathways. These findings illustrate the utility of recursive
      partitioning techniques in identifying biomarker combinations predictive of
      mortal outcomes in older adults, as well as the multiplicity of biological
      pathways to mortality in elderly populations.

PMID- 16983100
TI  - Health complaints following an air disaster: a "second disaster".

PMID- 16983101
TI  - World at work: Evidence based risk management of nail dust in chiropodists and
      podiatrists.

PMID- 16983102
TI  - What is the impact of shared decision making on treatment and outcomes for older
      women with breast cancer?
AB  - PURPOSE: Shared decision making (SDM) has been recommended as a standard of care,
      especially when there are treatment alternatives or uncertainty in outcomes.
      However, we know little about use of SDM in cancer care, and even less is known
      about SDM in older patients. We describe patient and physician determinants of
      SDM in older women with breast cancer and evaluate whether SDM is associated with
      treatment patterns or short-term outcomes of care. PATIENTS AND METHODS: Women
      age 67 or older treated for early stage breast cancer in 29 sites from five
      geographic regions comprise the study sample (N = 718). Data were obtained from
      patients by in-person and telephone interviews. Physician data were collected via
      survey, and medical records were reviewed to ascertain comorbidity and tumor
      characteristics. Random effects and logistic regression models were used to
      assess associations between SDM and other factors. RESULTS: Women who were age 67
      to 74 years (v 75 or older) were accompanied to consultation and who sought
      information reported the highest SDM, after considering covariates. While SDM was
      not associated with surgical treatment, greater SDM was associated with higher
      odds of having adjuvant treatment, controlling for clinical factors. Greater SDM
      was also associated with improved short-term satisfaction. CONCLUSION: SDM plays
      an important role in the process of care for older women with breast cancer.
      Physicians treating this growing population have a simple, but powerful tool for
      improving outcomes within their grasp-spending time to engage and involve older
      women in their breast cancer care.

PMID- 16983103
TI  - Fluorodeoxyglucose positron emission tomography for the preoperative staging of
      oral cavity cancers: only one piece of the puzzle.

PMID- 16983104
TI  - Treating breast cancer: the age old dilemma of old age.

PMID- 16983105
TI  - Prospective study of [18F]fluorodeoxyglucose positron emission tomography and
      computed tomography and magnetic resonance imaging in oral cavity squamous cell
      carcinoma with palpably negative neck.
AB  - PURPOSE: To assess the clinical usefulness of [(18)F]fluorodeoxyglucose positron
      emission tomography ([18F]FDG PET) as well as computed tomography (CT) or
      magnetic resonance imaging (MRI) in oral squamous cell carcinoma (SCC) patients
      with palpably negative neck. PATIENTS AND METHODS: In total, 134 oral SCC
      patients with palpably negative neck were prospectively evaluated with [18F]FDG
      PET, CT/MRI, and their visual correlation. Histopathologic analysis was used as
      the gold standard for assessment of these imaging techniques. RESULTS: Thirty
      five (26.1%) of our 134 patients were found to have neck metastases. On a level
      by-level basis, the sensitivity of [18F]FDG PET for nodal metastases was two-fold
      higher than that of CT/MRI (41.2% v 21.6%, respectively; P = .021). Visual
      correlation of [(18)F]FDG PET and CT/MRI yielded slightly higher sensitivity and
      specificity than [18F]FDG PET alone (47.1% v 41.2%, P = .25; 98.0% v 96.8%, P =
      .125, respectively). On a patient-by-patient basis, the sensitivity of [18F]FDG
      PET for neck metastases was 51.4% and increased to 57.1% after visual correlation
      with CT/MRI. The probabilities of occult neck metastasis after using [(18)F]FDG
      PET were 6.7% in T1 tumors, 10.8% in T2 tumors, 13.3% in T3 tumors, and 25% in T4
      tumors and decreased to 3.3% in T1 tumors and to 9.2% in T2 tumors after visual
      correlation with CT/MRI. CONCLUSION: [(18)F]FDG PET was superior to CT/MRI for
      detecting palpably occult neck metastasis of oral SCC. Because [(18)F]FDG PET
      could reduce the probability of occult neck metastasis to less than 15% in T1 to
      T3 tumors, it should be indicated for evaluation of these subpopulations.

PMID- 16983106
TI  - Breast cancer treatment of older women in integrated health care settings.
AB  - PURPOSE: A substantial literature describes age-dependent variations in breast
      cancer treatment, showing that older women are less likely to receive standard
      treatment than younger women. We sought to identify patient and tumor
      characteristics associated with the nonreceipt of standard primary tumor and
      systemic adjuvant therapies. PATIENTS AND METHODS: We studied 1,859 women age 65
      years or older with stage I and II breast cancer diagnosed between 1990 and 1994
      who were cared for in six geographically dispersed community-based health care
      systems. We collected demographic, tumor, treatment, and comorbidity data from
      electronic data sources, including cancer registry, administrative, and clinical
      databases, and from subjects' medical records. RESULTS: Women 75 years of age or
      older and women with higher comorbidity indices were more likely to receive
      nonstandard primary tumor therapy, to not receive axillary lymph node dissection,
      and to not receive radiation therapy after breast-conserving surgery (BCS). Asian
      women were less likely to receive BCS, and African American women were less
      likely to be prescribed tamoxifen. Although nonreceipt of most therapies was
      associated with a lower baseline risk of recurrence, an important minority of
      high-risk women (16% to 30%) did not receive guideline therapies. CONCLUSION: Age
      is an independent risk factor for nonreceipt of effective cancer therapies, even
      when comorbidity and risk of recurrence are taken into account. Information
      regarding treatment effectiveness in this age group and tools that allow
      physicians and patients to estimate the benefits versus the risks of therapies,
      taking into account age and comorbidity burden, are critically needed.

PMID- 16983107
TI  - Simultaneous chemoradiotherapy compared with radiotherapy alone after induction
      chemotherapy in inoperable stage IIIA or IIIB non-small-cell lung cancer: study
      CTRT99/97 by the Bronchial Carcinoma Therapy Group.
AB  - PURPOSE: The aim of this study was to examine whether, after preceding induction
      chemotherapy, simultaneous chemoradiotherapy is superior to radiotherapy alone.
      PATIENTS AND METHODS: Patients with non-small-cell lung cancer in inoperable
      stage IIIA or IIIB received induction chemotherapy with two cycles of paclitaxel
      200 mg/m2 and carboplatin area under the curve 6 every 3 weeks. Patients without
      progression at restaging after induction chemotherapy were randomly assigned to
      radiotherapy (60 Gy) or chemoradiotherapy (paclitaxel 60 mg/m2 weekly). The
      primary end point was overall survival; secondary end points were time to
      progression, response, and toxicity. RESULTS: Three hundred three patients
      entered the study, and 276 completed induction chemotherapy. Two hundred fourteen
      patients were randomly assigned (radiotherapy alone: n = 113; simultaneous
      chemoradiotherapy: n = 101). Median follow-up time of all randomly assigned
      patients was 13.6 months (interquartile range [IQR], 6.4 to 29.0 months), and
      median follow-up time of the subgroup of censored patients (n = 52) was 37.4
      months (IQR, 5.9 to 57.0 months; maximum, 76.1 months). Toxicities during the
      induction phase were mild. During radiotherapy, overall toxicity rates were not
      significantly different between the two arms. Median survival times in the
      radiotherapy group and chemoradiotherapy group were 14.1 months (95% CI, 11.8 to
      16.3 months) and 18.7 months (95% CI, 14.1 to 23.3 months; difference not
      statistically significant, P = .091). Median time to progression significantly
      favored simultaneous chemoradiotherapy (11.5 months; 95% CI, 8.3 to 14.7 months)
      versus radiotherapy alone (6.3 months; 95% CI, 5.0 to 7.6 months; P < .001, log
      rank test). CONCLUSION: Induction chemotherapy followed by chemoradiotherapy with
      weekly paclitaxel is feasible. Response, time to progression, and survival favor
      chemoradiotherapy compared with radiotherapy alone.

PMID- 16983108
TI  - Elderly patients benefit from second-line cytotoxic chemotherapy: a subset
      analysis of a randomized phase III trial of pemetrexed compared with docetaxel in
      patients with previously treated advanced non-small-cell lung cancer.
AB  - PURPOSE: Numerous prospective and retrospective studies have concluded that
      elderly patients (> or = 70 years old) achieve a similar survival benefit, with
      acceptable toxicity, from first-line cytotoxic chemotherapy for the treatment of
      advanced non-small-cell lung cancer (NSCLC) compared with their younger
      counterparts. However, few published data exist on the efficacy and tolerability
      of second-line cytotoxic therapy in this population. PATIENTS AND METHODS:
      Retrospective analysis of a large second-line trial was performed. Data from 571
      patients randomly assigned to docetaxel 75 mg/m2 or pemetrexed 500 mg/m2 every 3
      weeks were analyzed for efficacy and toxicity comparisons between age groups and
      treatment arms. RESULTS: Eighty-six of 571 patients (15%) were > or = 70 years
      old, similar to rates of elderly observed in the first-line setting. Elderly
      patients receiving pemetrexed (n = 47) or docetaxel (n = 39) had a median
      survival of 9.5 and 7.7 months compared with 7.8 and 8.0 months for younger
      patients receiving pemetrexed (n = 236) or docetaxel (n = 249), respectively.
      Elderly patients treated with pemetrexed had a longer time to progression and a
      longer survival than their counterpart patients treated with docetaxel (not
      statistically significant). Febrile neutropenia was less frequent in elderly
      patients treated with pemetrexed (2.5%) compared with docetaxel (19%; P = .025),
      with only one death as a result of toxicity (docetaxel arm). CONCLUSION: Elderly
      patient participation was similar to rates observed in the first-line setting.
      There was no significant difference in outcome or toxicity between elderly and
      younger patients. For elderly patients with advanced NSCLC and good performance
      status, second-line cytotoxic therapy is appropriate. In this subset, pemetrexed
      produced a more favorable toxicity profile.

PMID- 16983109
TI  - Phase II trial of lomustine plus temozolomide chemotherapy in addition to
      radiotherapy in newly diagnosed glioblastoma: UKT-03.
AB  - PURPOSE: To evaluate toxicity and efficacy of the combination of lomustine,
      temozolomide (TMZ) and involved-field radiotherapy in patients with newly
      diagnosed glioblastoma (GBM). PATIENTS AND METHODS: Thirty-one adult patients
      (median Karnofsky performance score 90; median age, 51 years) accrued in two
      centers received involved-field radiotherapy (60 Gy in 2-Gy fractions) and
      chemotherapy with lomustine 100 mg/m2 (day 1) and TMZ 100 mg/m2/d (days 2 to 6)
      with individual dose adjustments according to hematologic toxicity. RESULTS: A
      median of five courses (range, one to six courses) were delivered. WHO grade 4
      hematotoxicity was observed in five patients (16%) and one of these patients died
      as a result of septicemia. Nonhematologic toxicity included one patient with WHO
      grade 4 drug-induced hepatitis (leading to discontinuation of lomustine and TMZ)
      and one patient with WHO grade 2 lung fibrosis (leading to discontinuation of
      lomustine). The progression-free survival (PFS) rate at 6 months was 61.3%. The
      median PFS was 9 months (95% CI, 5.3 to 11.7 months), the median overall survival
      time (MST) was 22.6 months (95% CI, 12.5 to not assessable), the 2-year survival
      rate was 44.7%. O6-methylguanine-DNA methyltransferase (MGMT) gene-promoter
      methylation in the tumor tissue was associated with longer PFS (P = .014, log
      rank test) and MST (P = .037). CONCLUSION: The combination of lomustine, TMZ, and
      radiotherapy had acceptable toxicity and yielded promising survival data in
      patients with newly diagnosed GBM. MGMT gene-promoter methylation was a strong
      predictor of survival.

PMID- 16983110
TI  - Designing dose-escalation trials with late-onset toxicities using the time-to
      event continual reassessment method.
AB  - PURPOSE: The standard design for phase I trials of combined chemotherapy and
      radiation, which enters either three or six patients per dose level, has little
      statistical basis and is subject to opening and closing because of delayed
      toxicities that disrupt patient accrual. We compared the operating
      characteristics of this standard design and the time-to-event continual
      reassessment method (TITE-CRM) for dose-escalation trials of combination
      chemotherapy and radiation. METHODS: The operating characteristics were
      determined by Monte Carlo simulation of 60,000 phase I trials. RESULTS: Compared
      with the standard trial design, in studies with delayed toxicity (ie, where four
      or more patients are expected to enter onto the study during a single previously
      enrolled patient's observation for toxicity), TITE-CRM trials are significantly
      shorter when toxicity observation times are long, treat more patients at or above
      the maximum-tolerated dose, identify the maximum-tolerated dose (MTD) more
      accurately, and provide phase II information, but do not expose patients to
      significant additional risk. Estimation precision and overdose control of TITE
      CRM increase as the design assumptions more closely resemble the true state of
      nature, but are reduced if, for instance, the toxicity of treatment has been
      grossly underestimated. CONCLUSION: Compared with the standard design, if there
      is any prior knowledge concerning the toxicity profile of a treatment, TITE-CRM
      can leverage it to produce more accurate estimates of the MTD and does not expose
      patients to significant excess risk, but requires timely communication between
      clinical investigators, data managers, and study statisticians.

PMID- 16983111
TI  - MDM2 promoter polymorphism is associated with both an increased susceptibility to
      gastric carcinoma and poor prognosis.
AB  - PURPOSE: Recently, a single-nucleotide polymorphism in the MDM2 promoter (SNP309)
      has been found to lower the age of onset of tumors and increase the occurrence of
      multiple primary tumors in Li-Fraumeni syndrome, and accelerate the development
      of sporadic adult soft tissue sarcoma. The aim of this study was to determine
      whether SNP309 is associated with susceptibility to gastric carcinoma and its
      prognosis. PATIENTS AND METHODS: In a case-control study including 438 controls
      and 410 patients with sporadic gastric carcinoma, MDM2 SNP309 was genotyped.
      Serum pepsinogens (PGs) I and II were measured in 438 control subjects and 253
      cases selected from 410 patients. Tumor tissue was immunostained with p53 and
      examined for mutations in exons 5 to 8 of p53 using polymerase chain reaction
      based single strand conformational polymorphism analysis and direct sequencing.
      RESULTS: The risk of overall gastric carcinoma for SNP309 (G/G) was significantly
      increased when compared with T carriers (P = .039), especially carcinomas with
      extragastric tumors (P = .005), carcinoma with severe atrophic gastritis positive
      for PG assay (PG I level < 70 ng/mL and PG I/II < 3.0; P = .005), antral
      carcinoma (P = .020), intestinal-type carcinoma (P = .023), p53-immunopositive
      carcinoma (P = .007), and carcinoma with p53 mutations (P = .007). No significant
      difference in age at diagnosis was observed among genotypes. SNP309 (G/G) was an
      independent marker of poor overall survival in advanced carcinoma (hazard ratio,
      3.16; 95% CI, 1.22 to 8.20; P = .018). CONCLUSION: This study provides evidence
      supporting the association of SNP309 with gastric carcinogenesis via p53 tumor
      suppressor pathway, extragastric tumorigenesis, and poor prognosis.

PMID- 16983112
TI  - Randomized phase III study of exatecan and gemcitabine compared with gemcitabine
      alone in untreated advanced pancreatic cancer.
AB  - PURPOSE: Exatecan mesylate is a hexacyclic, water-soluble, topoisomerase-1
      inhibitor. Exatecan has single-agent and combination activity with gemcitabine in
      advanced pancreatic cancer. A multicenter, randomized, phase III trial comparing
      exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer
      was conducted. PATIENTS AND METHODS: Eligibility criteria included Karnofsky
      performance status > or = 60%, locally advanced or metastatic pancreatic
      adenocarcinoma, and no prior chemotherapy. Radiation alone for locally advanced
      disease was permitted. Patients were randomly assigned on a 1:1 basis. For the
      exatecan plus gemcitabine arm, exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2
      were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at
      1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3
      weeks of a 4-week cycle. Tumor assessment was performed every 6 weeks. The
      primary end point was overall survival. An intent-to-treat analysis was used.
      RESULTS: From August 2001 to January 2003, 349 patients were randomly assigned,
      175 to exatecan plus gemcitabine and 174 to gemcitabine alone. Twenty-four
      patients (6.9%) were not treated. The median survival time was 6.7 months for
      exatecan plus gemcitabine and 6.2 months for gemcitabine alone (P = .52). One
      complete response (CR; < 1%) and 11 partial responses (PRs; 6.3%) were observed
      in the exatecan plus gemcitabine treatment group, and one CR (< 1%) and eight PRs
      (4.6%) were observed in the gemcitabine-alone group. Grade 3 and 4 toxicities
      were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone
      arm; neutropenia (30% v 15%) and thrombocytopenia (15% v 4%). CONCLUSION:
      Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to
      overall survival in the first-line treatment of advanced pancreatic cancer.

PMID- 16983113
TI  - Diabetes and cardiovascular disease during androgen deprivation therapy for
      prostate cancer.
AB  - PURPOSE: Androgen deprivation therapy with a gonadotropin-releasing hormone
      (GnRH) agonist is associated with increased fat mass and insulin resistance in
      men with prostate cancer, but the risk of obesity-related disease during
      treatment has not been well studied. We assessed whether androgen deprivation
      therapy is associated with an increased incidence of diabetes and cardiovascular
      disease. PATIENTS AND METHODS: Observational study of a population-based cohort
      of 73,196 fee-for-service Medicare enrollees age 66 years or older who were
      diagnosed with locoregional prostate cancer during 1992 to 1999 and observed
      through 2001. We used Cox proportional hazards models to assess whether treatment
      with GnRH agonists or orchiectomy was associated with diabetes, coronary heart
      disease, myocardial infarction, and sudden cardiac death. RESULTS: More than one
      third of men received a GnRH agonist during follow-up. GnRH agonist use was
      associated with increased risk of incident diabetes (adjusted hazard ratio [HR],
      1.44; P < .001), coronary heart disease (adjusted HR, 1.16; P < .001), myocardial
      infarction (adjusted HR, 1.11; P = .03), and sudden cardiac death (adjusted HR,
      1.16; P = .004). Men treated with orchiectomy were more likely to develop
      diabetes (adjusted HR, 1.34; P < .001) but not coronary heart disease, myocardial
      infarction, or sudden cardiac death (all P > .20). CONCLUSION: GnRH agonist
      treatment for men with locoregional prostate cancer may be associated with an
      increased risk of incident diabetes and cardiovascular disease. The benefits of
      GnRH agonist treatment should be weighed against these potential risks.
      Additional research is needed to identify populations of men at highest risk of
      treatment-related complications and to develop strategies to prevent treatment
      related diabetes and cardiovascular disease.

PMID- 16983114
TI  - Confidence and uncertainty long after initial treatment for early prostate
      cancer: survivors' views of cancer control and the treatment decisions they made.
AB  - PURPOSE: The many years most men diagnosed with early prostate cancer live after
      diagnosis allow evolving assessments of their cancer control and their treatment
      choices, but little is known of these outcomes or the factors that influence
      them. PATIENTS AND METHODS: We surveyed an established, prospective cohort that
      had initiated treatment for early prostate cancer 4 to 8 years previously. We
      assessed perceived cancer control, quality of treatment decisions, and other
      domains of quality of life, along with treatment-related urinary, bowel, and
      sexual dysfunction. RESULTS: Most men reported high confidence in cancer control
      and their treatment decisions, but many reported misgivings about one or both.
      The diagnostic, treatment, and quality-of-life factors associated with these two
      outcomes were distinct. Perceived cancer control was lower among those with
      adverse medical factors: higher pretreatment Gleason scores, subsequent rises in
      prostate-specific antigen (PSA), and secondary androgen ablation therapy.
      Confidence in treatment decisions was unrelated to these factors and was higher
      in men who opted for radical prostatectomy or brachytherapy, reported close
      attention to current PSA, had high masculine self-esteem and little distress from
      sexual dysfunction, and were married. CONCLUSION: Although perceptions of cancer
      control and the quality of their treatment decisions are linked, men can
      distinguish between these two outcomes. They incorporate objective indicators of
      high risk and adverse outcomes when assessing their cancer control; confidence in
      treatment decisions represents a more complex psychosocial adjustment to the
      persistent uncertainty that originates with their diagnosis.

PMID- 16983115
TI  - Sentinel and nonsentinel node status in stage IB and II melanoma patients: two
      step prognostic indicators of survival.
AB  - PURPOSE: To evaluate the prognostic significance of sentinel node biopsy in the
      management of stage IB and II melanoma patients, and to evaluate the status of
      nonsentinel nodes as a "second step key factor" to assess the prognosis of these
      patients. PATIENTS AND METHODS: We conducted an analysis of data collected in a
      prospective database. RESULTS: From February 1994 to June 2005, 1,108 consecutive
      patients with stage IB and II melanoma were submitted to sentinel node biopsy;
      176 patients (15.9%) had occult node metastases. The frequency of positive nodes
      increased with increasing Breslow's thickness. The largest diameter of metastatic
      foci and their localization within the lymph node were associated with the risk
      of nonsentinel node metastases only. The 5-year survival of patients with
      positive sentinel nodes was 81.4% in patients with one positive node and 39.6% in
      patients with two positive nodes (P = .056). Multivariate analysis indicated that
      status of sentinel nodes is a key factor and that sex and Breslow's thickness
      maintain statistically significant relevance. Ulceration, which was associated
      with survival when considered as single factor (P < .001) had no impact on
      survival in the multivariate analysis (P = .10). To evaluate the relevance of
      metastases to nonsentinel nodes, we identified four groups of patients.
      CONCLUSION: Evaluation of the sentinel node is a useful procedure to identify
      patients to be submitted for complete lymph node dissection. The procedure makes
      it possible to assess the best prognosis of patients.

PMID- 16983116
TI  - Delayed nausea and vomiting continue to reduce patients' quality of life after
      highly and moderately emetogenic chemotherapy despite antiemetic treatment.
AB  - PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are major adverse
      effects of cancer chemotherapy. We compared the impact of acute (during the first
      24 hours postchemotherapy) and delayed (days 2 through 5 postchemotherapy) CINV
      on patients' quality of life (QoL) after highly or moderately emetogenic
      chemotherapy (HEC and MEC, respectively). PATIENTS AND METHODS: This prospective,
      multicenter, multinational study was conducted in 14 medical practices on cancer
      patients undergoing either HEC or MEC treatment. Patients recorded episodes of
      nausea and vomiting in a diary. Patients completed the Functional Living Index
      Emesis (FLIE) questionnaire at baseline and on day 6. RESULTS: A total of 298
      patients were assessable (67 HEC patients, 231 MEC patients). Emesis was reported
      by 36.4% of patients (13.2% acute, 32.5% delayed) and nausea by 59.7% (36.2%
      acute, 54.3% delayed). HEC patients reported significantly lower mean FLIE total
      score than MEC patients (95.5 v 107.8 respectively; P = .0049). Among all
      patients, the nausea score was significantly lower than the vomiting score (50.0
      and 55.3, respectively; P = .0097). Of the 173 patients who experienced neither
      vomiting nor nausea during the first 24 hours postchemotherapy, 22.9% reported an
      impact of CINV on daily life caused by delayed CINV. CONCLUSION: CINV continues
      to adversely affect patients' QoL despite antiemetic therapy even after treatment
      with only moderately emetogenic chemotherapy regimens, and even in the subgroup
      of patients who do not experience nausea and vomiting during the first 24 hours.
      On the basis of the FLIE results in this study, nausea had a stronger negative
      impact on patients' daily lives than vomiting.

PMID- 16983117
TI  - Patients' decision-making process regarding participation in phase I oncology
      research.
AB  - PURPOSE: This study assesses the decision-making process of patients enrolling in
      phase I oncology studies. PATIENTS AND METHODS: Participants were eligible if
      they had consented to participate in a phase I cancer study at one of five cancer
      centers, understood English, and were older than 18 years. Trained interviewers
      conducted structured in-person interviews. RESULTS: Of the 163 participants, 88%
      were white, 96% had health insurance, and 51% were college graduates or post
      graduates. Overall, 81% were aware of hospice, but only 6% had seriously
      considered hospice for themselves; 84% were aware of palliative care and 10%
      seriously considered it for themselves; and 7% considered getting no treatment at
      all. Overall, 75% reported moderate or a lot of pressure to participate in the
      phase I study because their cancer was growing, whereas 7% reported such pressure
      from the study investigators and 9% felt such pressure from their families. For
      63% of patients, the most important information for decision making was that the
      phase I drug killed cancer cells; only 12% reported that the adverse effects of
      the drug(s) was the most useful information. More than 90% of patients said they
      would still participate in the study even if the experimental drug caused serious
      adverse effects, including a 10% chance of dying. CONCLUSION: Patients are aware
      of many alternatives to phase I studies, but do not seriously consider them. Very
      few experience pressure from family or researchers to participate in research.
      Their main goal is to fight their cancer, and almost no adverse effect, including
      death, would dissuade them from enrolling.

PMID- 16983118
TI  - Longitudinal study of the relationship between chemoradiation therapy for non
      small-cell lung cancer and patient symptoms.
AB  - PURPOSE: Cancer patients undergoing aggressive therapy suffer from multiple
      nonspecific treatment-related symptoms. The goal of this prospective study was to
      establish a profile of the development of different symptoms over the time of
      therapy and to examine symptom-related functional interference in patients with
      non-small-cell lung cancer (NSCLC) undergoing concurrent chemoradiation therapy
      (CXRT). PATIENTS AND METHODS: Patients with locally advanced unresectable (stage
      II-IIIB) NSCLC were recruited for the study (N = 64). The M.D. Anderson Symptom
      Inventory (MDASI) was used to measure multiple symptoms before and weekly for 12
      weeks after the start of CXRT. Mixed-effect growth curve models were used to
      estimate symptom development during CXRT. RESULTS: Approximately 63% of patients
      suffered from moderate to severe levels of multiple symptoms by the end of CXRT.
      Symptom clusters with four development patterns appeared over the time of CXRT.
      With some variation between patients, all symptoms had a significant impact on
      the level of interference (all P < .001). Fatigue, distress, and sadness were the
      single strongest predictors of total symptom interference (each R2 > or = 0.49).
      Physical symptoms had greater impact on interference with function when they were
      moderate to severe, whereas affective symptoms had the largest effect on
      interference when they were mild to moderate. CONCLUSION: Longitudinal analysis
      identified symptom clusters that have different development patterns in NSCLC
      patients receiving CXRT, providing a base for more accurate symptom management
      and suggesting the need for further study to identify potential mechanisms that
      might lead to better symptom control or prevention.

PMID- 16983119
TI  - Type I pleuropulmonary blastoma: a report from the International Pleuropulmonary
      Blastoma Registry.
AB  - PURPOSE: Type I pleuropulmonary blastoma (PPB) is a rare, cystic lung neoplasm in
      infants characterized by subtle malignant changes and a good prognosis.
      Recurrences after type I PPB are usually advanced type II or type III neoplasms
      with a poor prognosis. This article describes the first collection of type I PPB
      cases, analyzes outcome based on treatments of surgery or surgery plus
      chemotherapy, and presents type I PPB management recommendations. PATIENTS AND
      METHODS: Type I PPB cases from the International PPB Registry and literature were
      evaluated using standard statistical methods for outcomes based on age at
      diagnosis, sex, thoracic side, surgical extent, length of follow-up,
      constitutional/familial disease, pre-existing lung cysts, intrathoracic findings,
      and treatments (surgery or surgery and chemotherapy). RESULTS: Thirty-eight type
      I PPB cases were identified: Registry (n = 30) and literature (n = 8). Twenty
      children had surgery alone; eight (40%) experienced recurrence; and four died.
      Eighteen children had surgery and adjuvant chemotherapy; one experienced
      recurrence and died. All recurrences were type II or III PPB. Recurrence-free
      survival was higher in the surgery + chemotherapy group (P = .01); overall
      survival did not differ (P = .18). The improved recurrence-free survival was
      found only in males. Four of nine children with recurrence survived. CONCLUSION:
      Adjuvant chemotherapy appears to benefit type I PPB patients. Benefit limited to
      males requires broader substantiation. Salvage after types II and III recurrence
      is poor (four of nine; 44%). A rigorous surveillance schedule after type I PPB
      diagnosis might detect early recurrence and be an acceptable alternative to
      adjuvant chemotherapy.

PMID- 16983120
TI  - Less toxicity by optimizing chemotherapy, but not by addition of granulocyte
      colony-stimulating factor in children and adolescents with acute myeloid
      leukemia: results of AML-BFM 98.
AB  - PURPOSE: To improve prognosis in children with acute myeloid leukemia (AML) by
      randomized comparisons of (1) two short consolidation cycles versus the Berlin
      Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the
      prophylactic administration of granulocyte colony-stimulating factor (G-CSF)
      versus no G-CSF. Further, therapy for standard risk patients was intensified by
      addition of a second induction, HAM (high-dose cytarabine and mitoxantrone).
      PATIENTS AND METHODS: Four hundred seventy-three patients younger than 18 years
      with de novo AML were enrolled in trial AML-BFM 98. Patients received five
      courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance
      therapy. RESULTS: Four hundred eighteen patients (88%) achieved remission.
      Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P =
      .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03).
      Both types of consolidation therapy led to similar outcome (event-free survival,
      51% v 50%), but in the two-cycle arm, treatment duration was shorter (median
      duration, 15 days), and treatment related mortality was lower (five v nine
      patients). G-CSF shortened neutropenia, but did not reduce the rate of severe
      infections. Intensification of induction therapy did not improve prognosis of
      standard-risk patients (event-free survival, 62% v 67%). CONCLUSION: Overall
      results were improved by neither the administration of G-CSF nor by cycle
      therapy; however, the latter was easier to perform. Compared with study AML-BFM
      93, therapy intensification with HAM in standard-risk patients did not result in
      improved prognosis. Future treatment designs have to balance intensification of
      treatment with higher toxicity, improve supportive care, and to consider
      alternative treatment strategies.

PMID- 16983121
TI  - Use of urine flow cytometry to verify relapse of Burkitt's lymphoma in the
      genitourinary system.

PMID- 16983122
TI  - HIV-associated anal squamous cell cancer: an otherwise preventable disease.

PMID- 16983124
TI  - Primary Burkitt's lymphoma of frontal bone: a rare presentation.

PMID- 16983123
TI  - Response and resistance in a non-small-cell lung cancer patient with an epidermal
      growth factor receptor mutation and leptomeningeal metastases treated with high
      dose gefitinib.

PMID- 16983125
TI  - Summaries for patients. Causes of death in people with AIDS in New York City
      between 1999 and 2004.

PMID- 16983126
TI  - Summaries for patients. Can doctors use self-reported sexual identity as a
      reliable indicator of sexual behavior?

PMID- 16983127
TI  - Causes of death among persons with AIDS in the era of highly active
      antiretroviral therapy: New York City.
AB  - BACKGROUND: Monitoring the full spectrum of causes of death among persons with
      AIDS is increasingly important as survival improves because of highly active
      antiretroviral therapy. OBJECTIVE: To describe recent trends in deaths due to HIV
      related and non-HIV-related causes among persons with AIDS, identify factors
      associated with these deaths, and identify leading causes of non-HIV-related
      deaths. DESIGN: Population-based cohort analysis. SETTING: New York City.
      PATIENTS: All adults (age > or =13 years) living with AIDS between 1999 and 2004
      who were reported to the New York City HIV/AIDS Reporting System and Vital
      Statistics Registry through 2004 (n = 68,669). MEASUREMENTS: Underlying cause of
      death on the death certificate. RESULTS: Between 1999 and 2004, the percentage of
      deaths due to non-HIV-related causes increased by 32.8% (from 19.8% to 26.3%; P =
      0.015). The age-adjusted mortality rate decreased by 49.6 deaths per 10,000
      persons with AIDS (P < 0.001) annually for HIV-related causes but only by 7.5
      deaths per 10 000 persons with AIDS (P = 0.004) annually for non-HIV-related
      causes. Of deaths due to non-HIV-related causes, 76% could be attributed to
      substance abuse, cardiovascular disease, or a non-AIDS-defining type of cancer.
      Compared with men who have sex with men, injection drug users had a statistically
      significantly increased risk for death due to HIV-related causes (hazard ratio,
      1.59 [95% CI, 1.49 to 1.70]) and non-HIV-related causes (hazard ratio, 2.54 [CI,
      2.24 to 2.87]). LIMITATIONS: Compared with autopsy and chart review, death
      certificates may lack specificity in the underlying cause of death or detailed
      clinical and treatment-related information. CONCLUSIONS: Non-HIV-related causes
      of death account for one fourth of all deaths of persons with AIDS.
      Cardiovascular disease, non-AIDS-defining cancer, and substance abuse account for
      most non-HIV-related deaths. Reducing deaths from these causes requires a shift
      in the health care model for persons with AIDS from a primary focus on managing
      HIV infection to providing care that addresses all aspects of physical and mental
      health.

PMID- 16983128
TI  - Noninvasive detection of coronary artery stenoses with multislice computed
      tomography or magnetic resonance imaging.
AB  - BACKGROUND: Multislice computed tomography (CT) and magnetic resonance imaging
      (MRI) are the main candidates for noninvasive coronary angiography; however,
      multislice CT, unlike MRI, exposes patients to radiation and an iodinated
      intravenous contrast agent. OBJECTIVE: To compare the diagnostic accuracy of
      multislice CT and MRI for noninvasive detection of clinically significant
      coronary stenoses (> or =50%). DESIGN: Prospective intention-to-diagnose study.
      SETTING: Single tertiary referral center, Berlin, Germany. PATIENTS: 129
      consecutive patients with suspected coronary artery disease. INTERVENTIONS:
      Multislice CT and MRI were both performed within a median of 1 day before
      conventional coronary angiography, which served as the reference standard.
      MEASUREMENTS: Diagnostic performance of multislice CT and MRI. RESULTS: 129
      patients completed the study. Altogether, 108 patients with 430 vessels could be
      examined with both multislice CT and MRI and were used for analysis. In the per
      patient analysis, the sensitivity of multislice CT (92% [95% CI, 82% to 96%]) was
      significantly higher than that of MRI (74% [CI, 61% to 83%]; P = 0.013). The
      sensitivity for detecting clinically significant stenoses was 82% for multislice
      CT and 54% for MRI (P < 0.001). Specificity and negative predictive value of
      multislice CT and MRI in the per-vessel analysis were 90% versus 87% (P = 0.73)
      and 95% versus 90% (P = 0.032), respectively. The effective radiation dose used
      with multislice CT (mean, 12.3 mSv [SD, 1.4]) in a consecutive subgroup of 73
      patients was not significantly different from that used with diagnostic cardiac
      catheterization (11.4 mSv [SD, 4.8]) (P = 0.169). Most patients (74%) indicated
      that they would prefer multislice CT for future diagnostic imaging (P < 0.001).
      LIMITATIONS: This was a single-center study with 129 patients. CONCLUSIONS: In
      patients referred for conventional coronary angiography, multislice CT compares
      favorably with MRI for noninvasive detection of coronary stenoses.

PMID- 16983129
TI  - Discordance between sexual behavior and self-reported sexual identity: a
      population-based survey of New York City men.
AB  - BACKGROUND: Persons reporting sexual identity that is discordant with their
      sexual behavior may engage in riskier sexual behaviors than those with concordant
      identity and behavior. The former group could play an important role in the
      spread of sexually transmitted diseases. OBJECTIVE: To describe discordance
      between self-described sexual identity and behavior among men who have sex with
      men and associations between identity-behavior and risk behaviors. DESIGN: Cross
      sectional, random digit-dialed telephone survey of health status and risk
      behaviors. SETTING: New York City. PARTICIPANTS: Population-based sample of 4193
      men. MEASUREMENTS: Concurrent measures of sexual identity and sexual behaviors,
      including number and sex of sex partners, condom use during last sexual
      encounter, and recent testing for HIV infection. Sex partner information was
      ascertained in a separate section from sexual identity; all participants were
      asked about the number of male sex partners and then were asked about the number
      of female sex partners in the past year. RESULTS: Of New York City men reporting
      a sexual identity, 12% reported sex with other men. Men who had sex with men
      exclusively but self-identified as heterosexual were more likely than their gay
      identified counterparts to belong to minority racial or ethnic groups, be foreign
      born, have lower education and income levels, and be married. These men were more
      likely than gay-identified men who have sex with men to report having only 1
      sexual partner in the previous year. However, they were less likely to have been
      tested for HIV infection during that time (adjusted prevalence ratio, 0.6 [95%
      CI, 0.4 to 0.9]) and less likely to have used condoms during their last sexual
      encounter (adjusted prevalence ratio, 0.5 [CI, 0.3 to 1.0]). LIMITATIONS: The
      survey did not sample groups that cannot be reached by using residential
      telephone services. CONCLUSIONS: Many New York City men who have sex with men do
      not identify as gay. Medical providers cannot rely on patients' self-reported
      identities to appropriately assess risk for HIV infection and sexually
      transmitted diseases; they must inquire about behavior. Public health prevention
      messages should target risky sexual activities rather than a person's sexual
      identity.

PMID- 16983130
TI  - Medication dispensing errors and potential adverse drug events before and after
      implementing bar code technology in the pharmacy.
AB  - BACKGROUND: Many dispensing errors made in hospital pharmacies can harm patients.
      Some hospitals are investing in bar code technology to reduce these errors, but
      data about its efficacy are limited. OBJECTIVE: To evaluate whether
      implementation of bar code technology reduced dispensing errors and potential
      adverse drug events (ADEs). DESIGN: Before-and-after study using direct
      observations. SETTING: Hospital pharmacy at a 735-bed tertiary care academic
      medical center. INTERVENTION: A bar code-assisted dispensing system was
      implemented in 3 configurations. In 2 configurations, all doses were scanned once
      during the dispensing process. In the third configuration, only 1 dose was
      scanned if several doses of the same medication were being dispensed.
      MEASUREMENTS: Target dispensing errors, defined as dispensing errors that bar
      code technology was designed to address, and target potential ADEs, defined as
      target dispensing errors that can harm patients. RESULTS: In the pre- and post
      bar code implementation periods, the authors observed 115,164 and 253,984
      dispensed medication doses, respectively. Overall, the rates of target potential
      ADEs and all potential ADEs decreased by 74% and 63%, respectively. Of the 3
      configurations of bar code technology studied, the 2 configurations that required
      staff to scan all doses had a 93% to 96% relative reduction in the incidence of
      target dispensing errors (P < 0.001) and 86% to 97% relative reduction in the
      incidence of potential ADEs (P < 0.001). However, the configuration that did not
      require scanning of every dose had only a 60% relative reduction in the incidence
      of target dispensing errors (P < 0.001) and an increased (by 2.4-fold) incidence
      of target potential ADEs (P = 0.014). There were several potentially life
      threatening ADEs involving intravenous dopamine and intravenous heparin in that
      configuration. LIMITATIONS: The authors used surrogate outcomes; did not mask
      assessors to the purpose of study; and excluded the controlled substance fill
      process (a process with low error rates at baseline) from the study, which may
      bias the combined decrease in error rates toward a larger magnitude. CONCLUSIONS:
      The overall rates of dispensing errors and potential ADEs substantially decreased
      after implementing bar code technology. However, the technology should be
      configured to scan every dose during the dispensing process.

PMID- 16983131
TI  - Narrative review: initial management of newly diagnosed, early-stage chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia is one of the most common malignant lymphoid
      diseases in the western world and is frequently diagnosed by internists. There
      have been clinically significant changes in method of diagnosis, prognostic
      tools, supportive care, and treatment over the past 2 decades. Most patients with
      chronic lymphocytic leukemia now have Rai stage 0 or I disease at diagnosis.
      Patients with early-stage disease are a heterogeneous group: Approximately 30% to
      50% will have accelerated disease progression, and the remainder may live for
      decades and possibly never require therapy. Recent insights into the biological
      characteristics of leukemic B cells have led to the discovery of new prognostic
      tools (immunoglobulin variable-region heavy chain gene mutation status,
      cytogenetic abnormalities assessed by fluorescent in situ hybridization, and Z
      chain-associated protein kinase-70 protein expression) that can identify patients
      with early-stage disease who are at high risk for early disease progression.
      These tools allow physicians to individualize counseling, follow-up, and
      management on the basis of disease risk. In addition, new treatments developed
      over the past 2 decades (purine nucleoside analogues, monoclonal antibodies, and
      combination chemoimmunotherapy regimens) have dramatically improved response
      rates and appear to prolong survival. In this review, the authors discuss the
      current work-up of lymphocytosis and highlight how to use recently identified
      prognostic tools to stratify risk in patients with newly diagnosed, early-stage
      chronic lymphocytic leukemia. Recommendations for patient counseling, follow-up,
      supportive care, and initial treatment are presented for each risk category.

PMID- 16983132
TI  - Narrative review: the U.S. Pharmacopeia and model guidelines for Medicare Part D
      formularies.
AB  - The Medicare Prescription Drug, Improvement, and Modernization Act of 2003
      includes a provision directing the Secretary of the U.S. Department of Health and
      Human Services to request that the U.S. Pharmacopeia (USP) develop a list of
      categories and classes (the USP Model Guidelines) that can be used by
      prescription drug plans in developing their formularies for the Part D
      prescription drug benefit. The Centers for Medicare & Medicaid Services (CMS)
      used the Model Guidelines and USP's related listing, termed the Formulary Key
      Drug Types, to evaluate prescription drug plan formularies submitted by
      prescription drug plan sponsors intending to provide the new Part D benefit. This
      article recounts how USP's all-volunteer Model Guidelines Expert Committee
      developed the USP Model Guidelines and Formulary Key Drug Types, working under a
      cooperative agreement with CMS in response to the Secretary's request. The Model
      Guidelines and Formulary Key Drug Types are updated annually to reflect advances
      in evidence-based medicine, thereby offering timely guidance to CMS and to
      prescription drug plans based on USP's demonstrated expertise in setting
      standards.

PMID- 16983133
TI  - Update in allergy and immunology.

PMID- 16983134
TI  - Rapid HIV testing at home: does it solve a problem or create one?
AB  - The U.S. Food and Drug Administration (FDA) is considering approval of an over
      the-counter, rapid HIV test for home use. To date, testimony presented before the
      FDA has been overwhelmingly supportive. Advocates have argued enthusiastically
      that there is value in empowering individuals to manage their HIV risks and have
      suggested that the availability of a rapid home HIV test will dramatically
      increase rates of disease detection in communities that have proven difficult to
      reach and to link to appropriate care. The authors offer a more cautious
      perspective. According to what is already known about the market demand for over
      the-counter HIV testing kits, their costs, and the performance of rapid HIV tests
      in that market, the authors do not anticipate that the rapid home test will have
      a profound impact either on the HIV public health crisis or on the populations in
      greatest need. Home HIV testing will attract a predominantly affluent clientele,
      composed disproportionately of HIV-uninfected new couples and "worried well"
      persons, as well as very recently infected persons with undetectable disease. The
      authors illustrate how testing in these populations may have the perverse effect
      of increasing both false-positive and false-negative results. A poorly
      functioning home HIV test may thereby undermine confidence in the reliability of
      HIV testing more generally and weaken critical efforts to expand HIV detection
      and linkage to lifesaving care for the estimated 300,000 U.S. citizens with
      unidentified HIV infection.

PMID- 16983135
TI  - The changing face of HIV care: common things really are common.

PMID- 16983136
TI  - Who is a candidate for noninvasive coronary angiography?

PMID- 16983137
TI  - Surveying the dying: medical epidemiology and the terminally ill.

PMID- 16983138
TI  - Preventing scientific fraud.

PMID- 16983139
TI  - Preventing scientific fraud.

PMID- 16983140
TI  - Severe hepatotoxicity of telithromycin.

PMID- 16983141
TI  - Preventing scientific fraud.

PMID- 16983142
TI  - Symptomatic myopathy due to red yeast rice.

PMID- 16983143
TI  - An RNA ligase-mediated method for the efficient creation of large, synthetic
      RNAs.
AB  - RNA ligation has been a powerful tool for incorporation of cross-linkers and
      nonnatural nucleotides into internal positions of RNA molecules. The most widely
      used method for template-directed RNA ligation uses DNA ligase and a DNA splint.
      While this method has been used successfully for many years, it suffers from a
      number of drawbacks, principally, slow and inefficient product formation and slow
      product release, resulting in a requirement for large quantities of enzyme. We
      describe an alternative technique catalyzed by T4 RNA ligase instead of DNA
      ligase. Using a splint design that allows the ligation junction to mimic the
      natural substrate of RNA ligase, we demonstrate several ligation reactions that
      appear to go nearly to completion. Furthermore, the reactions generally go to
      completion within 30 min. We present data evaluating the relative importance of
      various parameters in this reaction. Finally, we show the utility of this method
      by generating a 128-nucleotide pre-mRNA from three synthetic
      oligoribonucleotides. The ability to ligate synthetic or in vitro transcribed RNA
      with high efficiency has the potential to open up areas of RNA biology to new
      functional and biophysical investigation. In particular, we anticipate that site
      specific incorporation of fluorescent dyes into large RNA molecules will yield a
      wealth of new information on RNA structure and function.

PMID- 16983144
TI  - Differential effects of PER2 phosphorylation: molecular basis for the human
      familial advanced sleep phase syndrome (FASPS).
AB  - PERIOD (PER) proteins are central components within the mammalian circadian
      oscillator, and are believed to form a negative feedback complex that inhibits
      their own transcription at a particular circadian phase. Phosphorylation of PER
      proteins regulates their stability as well as their subcellular localization. In
      a systematic screen, we have identified 21 phosphorylated residues of mPER2
      including Ser 659, which is mutated in patients suffering from familial advanced
      sleep phase syndrome (FASPS). When expressing FASPS-mutated mPER2 in oscillating
      fibroblasts, we can phenocopy the short period and advanced phase of FASPS
      patients' behavior. We show that phosphorylation at Ser 659 results in nuclear
      retention and stabilization of mPER2, whereas phosphorylation at other sites
      leads to mPER2 degradation. To conceptualize our findings, we use mathematical
      modeling and predict that differential PER phosphorylation events can result in
      opposite period phenotypes. Indeed, interference with specific aspects of mPER2
      phosphorylation leads to either short or long periods in oscillating fibroblasts.
      This concept explains not only the FASPS phenotype, but also the effect of the
      tau mutation in hamster as well as the doubletime mutants (dbtS and dbtL ) in
      Drosophila.

PMID- 16983146
TI  - Higher plasma docosahexaenoic acid is associated with reduced progression of
      coronary atherosclerosis in women with CAD.
AB  - Fish intake, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and in some
      cases alpha-linolenic acid (ALA) have been associated with reduced risk of
      cardiovascular events and death. The association between n-3 fatty acids in
      plasma lipids and the progression of coronary artery atherosclerosis was assessed
      among women with established coronary artery disease (CAD). A prospective cohort
      study involved postmenopausal women (n = 228) participating in the Estrogen
      Replacement and Atherosclerosis Trial. Quantitative coronary angiography was
      performed at baseline and after 3.2 +/- 0.6 (mean +/- SD) years. Women with
      plasma phospholipid (PL) DHA levels above the median, compared with below,
      exhibited less atherosclerosis progression, as expressed by decline in minimum
      coronary artery diameter (-0.04 +/- 0.02 and -0.10 +/- 0.02 mm, respectively; P =
      0.007) or increase in percentage stenosis (1.34 +/- 0.76% and 3.75 +/- 0.74%,
      respectively; P = 0.006), and had fewer new lesions [2.0% (0.5-3.5%) of measured
      segments (95% confidence interval) and 4.2% (2.8-5.6%), respectively; P = 0.009]
      after adjustments for cardiovascular risk factors. Similar results were observed
      for DHA in the triglycerides (TGs). EPA and ALA in plasma lipids were not
      significantly associated with atherosclerosis progression. Consistent with higher
      reported fish intake, higher levels of plasma TG and PL DHA are associated with
      less progression of coronary atherosclerosis in postmenopausal women with CAD.

PMID- 16983145
TI  - A cancer cell metalloprotease triad regulates the basement membrane
      transmigration program.
AB  - Carcinoma cells initiate the metastatic cascade by inserting invasive pseudopodia
      through breaches in the basement membrane (BM), a specialized barrier of cross
      linked, extracellular matrix macromolecules that underlies epithelial cells and
      ensheaths blood vessels. While BM invasion is the sine qua non of the malignant
      phenotype, the molecular programs that underlie this process remain undefined. To
      identify genes that direct BM remodeling and transmigration, we coupled high
      resolution electron microscopy with an ex vivo model of invasion that phenocopies
      the major steps observed during the transition of carcinoma in situ to frank
      malignancy. Herein, a triad of membrane-anchored proteases, termed membrane type
      1, type-2, and type-3 metalloproteinases, are identified as the triggering agents
      that independently confer cancer cells with the ability to proteolytically efface
      the BM scaffolding, initiate the assembly of invasive pseudopodia, and propagate
      transmigration. These studies characterize the first series of gene products
      capable of orchestrating the entire BM remodeling program that distinguishes the
      carcinomatous phenotype.

PMID- 16983147
TI  - Increased nonsterol isoprenoids, dolichol and ubiquinone, in the Smith-Lemli
      Opitz syndrome: effects of dietary cholesterol.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an inherited autosomal recessive cholesterol
      deficiency disorder. Our studies have shown that in SLOS children, urinary
      mevalonate excretion is normal and reflects hepatic HMG-CoA reductase activity
      but not ultimate sterol synthesis. Hence, we hypothesized that in SLOS there may
      be increased diversion of mevalonate to nonsterol isoprenoid synthesis. To test
      our hypothesis, we measured urinary dolichol and ubiquinone, two nonsterol
      isoprenoids, in 16 children with SLOS and 15 controls, all fed a low-cholesterol
      diet. The urinary excretion of both dolichol (P < 0.002) and ubiquinone (P <
      0.02) in SLOS children was 7-fold higher than in control children, whereas
      mevalonate excretion was comparable. In a subset of 12 SLOS children, a high
      cholesterol diet decreased urinary mevalonate excretion by 61% (P < 0.001),
      dolichol by 70% (P < 0.001), and ubiquinone by 67% (P < 0.03). Our hypothesis
      that in SLOS children, normal urinary mevalonate excretion results from increased
      diversion of mevalonate into the production of nonsterol isoprenoids is
      supported. Dietary cholesterol supplementation reduced urinary mevalonate and
      nonsterol isoprenoid excretion but did not change the relative ratios of their
      excretion. Therefore, in SLOS, a secondary peripheral regulation of isoprenoid
      synthesis may be stimulated.

PMID- 16983149
TI  - Centrosymmetric and pseudo-centrosymmetric structures refined as non
      centrosymmetric.
AB  - The behaviour of the Flack parameter for centrosymmetric and pseudo
      centrosymmetric crystal structures based on crystal structures published as being
      non-centrosymmetric is presented. It is confirmed for centrosymmetric structures
      that the value obtained for the Flack parameter is critically dependent on the
      Friedel coverage of the intensity data, approaching 0.5 for a coverage of 100%
      and sticking near the starting value for a coverage of 0%. For pseudo
      centrosymmetric structures, even those very close to being centrosymmetric, it is
      found that it is often possible to obtain significant values of the Flack
      parameter. A theoretical basis for this surprising result is established. It has
      also been possible to establish an a priori estimate of the standard uncertainty
      of the Flack parameter based only on the chemical composition of the compound and
      the wavelength of the radiation. The paper concludes with preliminary
      presentations of bias in the Flack parameter and of inconsistent chemical and
      crystallographic data.

PMID- 16983148
TI  - Reconstructing contiguous regions of an ancestral genome.
AB  - This article analyzes mammalian genome rearrangements at higher resolution than
      has been published to date. We identify 3171 intervals, covering approximately
      92% of the human genome, within which we find no rearrangements larger than 50
      kilobases (kb) in the lineages leading to human, mouse, rat, and dog from their
      most recent common ancestor. Combining intervals that are adjacent in all
      contemporary species produces 1338 segments that may contain large insertions or
      deletions but that are free of chromosome fissions or fusions as well as
      inversions or translocations >50 kb in length. We describe a new method for
      predicting the ancestral order and orientation of those intervals from their
      observed adjacencies in modern species. We combine the results from this method
      with data from chromosome painting experiments to produce a map of an early
      mammalian genome that accounts for 96.8% of the available human genome sequence
      data. The precision is further increased by mapping inversions as small as 31 bp.
      Analysis of the predicted evolutionary breakpoints in the human lineage confirms
      certain published observations but disagrees with others. Although only a few
      mammalian genomes are currently sequenced to high precision, our theoretical
      analyses and computer simulations indicate that our results are reasonably
      accurate and that they will become highly accurate in the foreseeable future. Our
      methods were developed as part of a project to reconstruct the genome sequence of
      the last ancestor of human, dogs, and most other placental mammals.

PMID- 16983150
TI  - Bond analyses of borates from the Inorganic Crystal Structure Database.
AB  - Various fundamental building blocks (FBBs) are observed in the crystallographic
      structures of oxoborates available in the Inorganic Crystal Structure Database,
      Version 1.3.3 (2004); the occurrence of borate groups with low complexity is
      dominant. Bond-valence parameters d(0) of B-O bonds in 758 oxoborates with
      various FBBs have been calculated using the bond-valence sum model. Some
      discrepancies in the d(0) values obviously occur if the detailed configurations
      of FBBs in borate crystals are considered; d(0) is sensitive to the chemical
      bonding structure of B atoms in the crystallographic framework. Moreover, d(0)
      values are affected by the existence of interstitial atoms and the substitution
      of other anionic groups. In addition, the d(0) parameters for B-N, B-S, B-P and B
      F bonds are also calculated statistically. Some suitable d(0) data for various
      borate FBBs are recommended according to their particular configurations,
      especially for those with low complexity. On the basis of the proposed linear
      relationship between calculated nonlinear optical (NLO) coefficients of borates
      and the current d(0) values for various FBBs, it is found that the d(0) values
      may be regarded as a useful parameter for pre-investigating the NLO properties of
      borates, leading to an efficient structural evaluation and design of novel
      borates.

PMID- 16983151
TI  - Modulated corrugations in the crystal structure of the superconductor CaAlSi.
AB  - We report the crystal structure analyses of CaAlSi from single-crystal and powder
      X-ray diffraction and the existence of two commensurately modulated phases, a
      sixfold and a fivefold modulated structure. This polymorphism seems to be
      correlated to the thermal history of the sample. We describe both modulated
      structures using a three-dimensional and a (3 + 1)-dimensional formalism.

PMID- 16983152
TI  - Structural phase transition and hydrogen ordering of TlH2PO4 at low temperature.
AB  - The crystal structure of TlH(2)PO(4) (TDP) has been studied at low temperature.
      The lattice parameters were derived from high-resolution X-ray powder diffraction
      in the temperature range between 8 and 300 K. A detailed crystal structure
      analysis of the antiferroelectric low-temperature phase TDP-III has been
      performed based on neutron diffraction data measured at 210 K on a twinned
      crystal consisting of two domain states. The structure model in the triclinic
      space group P?bar 1 is characterized by a complete ordering of all the H atoms in
      the asymmetric O-H...O hydrogen bonds. The phase transition from the ferroelastic
      TDP-II to the antiferroelectric TDP-III phase at 229.5 +/- 0.5 K is only slightly
      of first order and shows no detectable hysteresis effects. Its mechanism is
      driven by the hydrogen ordering between the partially ordered TDP-II state and
      the completely ordered TDP-III state. The polymorphism of TDP and the fully
      deuterated TlD(2)PO(4) (DTDP) is presented in the form of group-subgroup
      relations between the different space groups.

PMID- 16983153
TI  - Structural characterization of Ni2Si pseudoepitaxial transrotational structures
      on [001] Si.
AB  - The formation of pseudoepitaxial transrotational structures has been observed
      during the early stage of the reaction of thin Ni layers on [001] Si substrates.
      During the reaction, large Ni(2)Si domains, characterized by single bending
      contours, establish a close relationship with the silicon lattice. The silicide
      domain consists of a core region, along the bending contour, where the silicide
      layer has grown epitaxially with silicon. Outside the core, the planes, at first
      parallel to the bending contour, continuously bend over the range 15-20 degrees ,
      whilst those at 90 degrees remain aligned with silicon across the interface.
      Owing to the cylindrical symmetry of those transrotational structures,
      transmission electron microscopy analyses provided direct evidence of the bending
      phenomenon and allowed a complete description of the fully relaxed domain
      structure. A non-conventional mechanism of strain relaxation has been proposed,
      which is competitive with respect to the usual formation of misfit dislocations.
      The competitive phenomenon consists of Ni(2)Si lattice bending and rearrangement
      of the interface to minimize the Gibbs free energy of the domain.

PMID- 16983154
TI  - Superspace description of the homologous series Ga4Tim-4O2m-2 with the
      crystallographic shear structure based on that of rutile.
AB  - A generalized approach is proposed for the structure description of the
      homologous series Ga(4)Ti(m-4)O(2m-2) with crystallographic shear (CS) structures
      based on that of rutile. A (3 + 1)-dimensional model for an ideal CS structure is
      built up in connection with the CS operation in three-dimensional space. Its
      structural parameters are determined by m, the shear plane and the shear vector.
      The Rietveld fitting of the X-ray diffraction profile of Ga(4)Ti(13)O(32) (m =
      17) was successfully carried out using the ideal CS structure as an initial
      model, where modulation functions of atomic positions are inherently
      discontinuous and sawtooth-like. The deviation of a real structure from the ideal
      one was described by a few additional Fourier terms. This method was confirmed to
      be efficient for reducing the number of structural parameters required in the
      refinement in comparison to the conventional three-dimensional description.

PMID- 16983155
TI  - Bond-valence parameters of lanthanides.
AB  - Ln-O and Ln-N bond-valence parameters have been computed in coordination
      complexes for lanthanides (Ln) at oxidation states other than +3 (Ce(IV), Sm(II),
      Eu(II) and Yb(II)). Moreover, Ln-Cl, Ln-S and Ln-C(pi-bonded) bond-valence
      parameters are presented, as calculated for coordination compounds. In general,
      the bond-valence parameters decrease in the order Ln-O > Ln-C > Ln-N > Ln-Cl > Ln
      S. It has been found that the values of bond-valence parameters decrease with
      increasing lanthanide atomic number for coordination compounds. As expected, the
      values of lanthanide-oxygen and lanthanide-nitrogen bond-valence parameters
      diminish with increasing lanthanide oxidation state. Several examples are given
      where the total valence of the lanthanide ion is apparently incorrectly assigned,
      as well as cases where bond-valence method calculations confirm the doubtful
      oxidation state assignment.

PMID- 16983156
TI  - LnOn coordination polyhedra (Ln = La-Lu) in crystal structures.
AB  - Voronoi-Dirichlet (VD) polyhedra and the method of intersecting spheres were used
      to analyze the crystal structures of 2,917 compounds containing 3,903
      crystallographically non-equivalent types of LnO(n) polyhedra (Ln = La-Lu). It
      was established that Ln coordination numbers (CN) vary from 3 to 12, and 20 types
      of coordination polyhedra are present in the structures. Despite the great
      diversity of CN and types of coordination polyhedra, the volume of the VD
      polyhedron was found to depend only on the identity of the Ln atom and its
      oxidation state.

PMID- 16983157
TI  - Specific twin junctions in doped zirconia.
AB  - The effect of different dopant cations on the phase transformations of the
      initially stabilized supersaturated tetragonal ZrO(2) phase during various heat
      treatments has been studied. The obtained fraction of monoclinic grains develop
      twinned structures, but there is still a lack of information about the character
      of grain boundaries formed in doped monoclinic solid solutions. The inspection of
      particular selected-area electron diffraction patterns provides an alternative
      method with respect to high-resolution electron microscopy or electron back
      scattered diffraction for characterizing different twin junctions in various
      doped zirconia systems. The classification of these special twins is based on the
      coincidence site lattice concept.

PMID- 16983158
TI  - Structure and phase transition of the Se-rich variety of antimonpearceite,
      [(Ag,Cu)6(Sb,As)2(S,Se)7][Ag9Cu(S,Se)2Se2].
AB  - The crystal structure of a Se-rich antimonpearceite has been solved and refined
      by means of X-ray diffraction data collected at temperatures above (room
      temperature) and below (120 K) an ionic conductivity-induced phase transition.
      Both structure arrangements consist of the stacking of
      [(Ag,Cu)(6)(Sb,As)(2)(S,Se)(7)](2-) A (A') and [Ag(9)Cu(S,Se)(2)Se(2)](2+) B (B')
      module layers in which Sb forms isolated SbS(3) pyramids typically occurring in
      sulfosalts; copper links two S atoms in a linear coordination, and silver
      occupies sites with coordination ranging from quasi-linear to almost tetrahedral.
      In the ionic-conducting form, at room temperature, the silver d(10) ions are
      found in the B (B') module layer along two-dimensional diffusion paths and their
      electron densities described by means of a combination of a Gram-Charlier
      development of the atomic displacement factors and a split-atom model. The
      structure resembles that of pearceite, except for the presence of both specific
      (Se) and mixed (S, Se) sites. In the low-temperature ;ordered' phase at 120 K the
      silver d(10) ions of the B (B') module layer are located in well defined sites
      with mixed S-Se coordination ranging from quasi-linear to almost tetrahedral. The
      structure is then similar to that of 222-pearceite but with major differences,
      specifically its cell metric, symmetry and local arrangement in the B (B') module
      layer.

PMID- 16983159
TI  - First (3 + 2)-dimensional superspace approach to the structure of levyclaudite
      (Sb), a member of the cylindrite-type minerals.
AB  - The structure of synthetic levyclaudite-(Sb), approximately (Pb(1 -
      y)Sb(y)S)(1.357)[Sn(1 - x)(Cu(2))(x)S(2)], has been determined by single-crystal
      X-ray diffraction on the basis of the (3 + 2)-dimensional superspace approach.
      This misfit-layer compound, of the cylindrite type, results from the combination
      of two heavily modulated triclinic Q and H subsystems with a common q wavevector
      and only one shared reciprocal axis (stacking direction). The Q pseudo-tetragonal
      layer, approximately (Pb(0.70)Sb(0.30)S), derived from the NaCl archetype, is
      positively charged; the H pseudo-hexagonal layer, approximately
      (Sn(0.85)Cu(0.30)S(2)), derived from the CdI(2) archetype, is negatively charged,
      owing to the replacement of Sn(4+) in an octahedral coordination by Cu(+) pairs
      in an opposite triangular coordination. The analysis shows a strong transverse
      displacive modulation of the two layers, referred to as a 'mondulation',
      correlated to a maximal Sb site occupation factor in the concavity of the Q layer
      undulation. The wavelength control of the ;mondulation' obeys the vernier
      principle (14c(Q) congruent with 13c(H)), which would correspond to an energy
      minimization through a charge transfer density modulation wave, common to all two
      dimensional misfit-layer inorganic compounds.

PMID- 16983160
TI  - Commensurate (C6H14N2)2[Mo8O26] * 4H2O and incommensurate (C6H14N2)2[Mo8O26] *
      4.66H2O: a structural versatility linked to solvent content.
AB  - The syntheses and structure determinations by means of single-crystal X-ray
      diffraction of commensurate (C(6)H(14)N(2))(2)[Mo(8)O(26)] * 4H(2)O and
      incommensurate (C(6)H(14)N(2))(2)[Mo(8)O(26)] * 4.66H(2)O, two new organic
      inorganic hybrid compounds based on polyoxomolybdates and differing in their
      solvent content, are reported. Given the important disorder observed in the
      latter compound, only a combination of non-harmonic waves, crenel functions and
      TLS tensors offered a good modelling of the structure.
      (C(6)H(14)N(2))(2)[Mo(8)O(26)] * nH(2)O results from the self-assembly of
      [Mo(8)O(26)](4-) anionic chains, C(6)H(14)N(2)(2+) (H(2)DABCO(2+)) cations and
      water molecules. The [Mo(8)O(26)](4-) chain is built from gamma-[Mo(8)O(28)](8-)
      octamolybdate clusters, connected to each other through corner sharing. In both
      compounds, the [Mo(8)O(26)](4-) chains are separated, in a similar way, by the
      H(2)DABCO(2+) subunits, acting as charge-compensating cations, and by the water
      molecules. The orientation of the H(2)DABCO(2+) cations is shown to be different
      from what has been observed previously in monoclinic (H(2)DABCO)(2)[Mo(8)O(26)] *
      4H(2)O, and therefore to give a different network of hydrogen bonds.

PMID- 16983161
TI  - Stoichiometry-dependent structures: an X-ray and neutron single-crystal
      diffraction study of the effect of reaction stoichiometry on the crystalline
      products formed in the potassium-cyanurate system.
AB  - Reaction of cyanuric acid (C(3)H(3)N(3)O(3); neutral form CYH(3); anionic form
      CYH_2;-; dianionic form CYH(2-)) with K(2)CO(3) or KOH in aqueous solution gave
      three different crystalline products, according to the reaction stoichiometry
      used. The structures of two products were easily determined by single-crystal X
      ray diffraction: [K(CYH(2))(H(2)O)], (1), of which the crystal structure is
      already known [Marsh, R. E. et al. (2002). Acta Cryst. B58, 62-77], and
      [K(2)(CYH)], (2), a highly symmetrical and dense structure. Further
      stoichiometric variation produced another new complex, (3), and reaction of
      Rb(2)CO(3) with CYH(3) yielded a further product, (4), which was found to be
      isostructural with (3). Determination of the structures of (3) and (4) by X-ray
      diffraction gave a result that was chemically unreasonable owing to a charge
      imbalance, with the asymmetric unit apparently containing 2- against 1.5+
      (partial charges as the result of crystallographic mirror symmetry). A single
      crystal neutron diffraction analysis carried out on a fully deuterated sample of
      (3) revealed the presence of a supercell, with the c axis doubled compared with
      the X-ray result. Subsequent refinement of the structure with this supercell
      showed that it is the result of just two D atoms breaking crystallographically
      imposed mirror symmetry, which is otherwise essentially observed by the rest of
      the structure. This minor deviation from pseudo-symmetry could not be identified
      by X-ray diffraction. Thus, single-crystal neutron diffraction data revealed that
      the true chemical formula of the structure of (3) [and presumably also of the
      isostructural (4) with Rb instead of K and H instead of D], is
      [K(3)(C(3)D(2)N(3)O(3))(3)(C(3)D(3)N(3)O(3))(D(2)O)(4)], the deuterated form of
      [K(3)(CYH(2))(3)(CYH(3))(H(2)O)(4)].

PMID- 16983162
TI  - Two-dimensional metal-organic frameworks containing linear dicarboxylates.
AB  - The solvothermal synthesis of four two-dimensional metal-organic frameworks
      containing linear dicarboxylic acids as ligands for Zn(II) centres is described.
      Zn(BDC)(DMF) [(1) where BDC = benzene-1,4-dicarboxylic acid; DMF = N,N
      dimethylformamide] adopts a common paddlewheel motif leading to a 4(4) grid
      network, whereas Zn(3)(BDC)(3)(EtOH)(2) (2), Zn(3)(BDC)(3)(H(2)O)(2) * 4DMF (3)
      and Zn(3)(BPDC)(3)(DMF)(2) * 4DMF (4) each form networks with the relatively
      uncommon 3(6) topology based upon Zn(3)(O(2)CR)(6) secondary building units. All
      contain coordinated solvent molecules, namely DMF [(1) and (4)], ethanol (2) or
      H(2)O (3). Comparison of structures (2) and (3) illustrates a clay-like
      flexibility in interplanar spacing which sheds light on the ability of the
      Zn(3)(BDC)(3) framework to undergo desolvation and uptake of small solvent and
      gas molecules.

PMID- 16983163
TI  - High-pressure neutron diffraction study of L-serine-I and L-serine-II, and the
      structure of L-serine-III at 8.1 GPa.
AB  - The hydrostatic compression of L-serine-d(7) has been studied to 8.1 GPa by
      neutron powder diffraction. Over the course of this pressure range the compound
      undergoes two phase transitions, the first between 4.6 and 5.2 GPa, yielding L
      serine-II, and the second between 7.3 and 8.1 GPa, yielding L-serine-III. All
      three polymorphs are orthorhombic, P2(1)2(1)2(1), and feature chains of serine
      molecules connected via head-to-tail ND...O hydrogen bonds formed between
      ammonium and carboxylate groups. The chains are linked into a ribbon by a second
      set of ND...O hydrogen bonds. The hydroxyl moieties are distributed along the
      outer edges of the ribbon and in phase I they connect the ribbons into a layer by
      chains of OD...OD hydrogen bonds. The layers are connected together by a third
      set of ND...O hydrogen bonds, forming R;3_4(14) rings with substantial voids at
      their centres. In the transition from phase I to II these voids begin to close
      up, but at the cost of breaking the OD...OD chains. The OD...OD hydrogen bonds
      are replaced by shorter OD...O hydrogen bonds to carboxylate groups. At 7.3 GPa
      the O...O distance in the OD...O hydrogen bonds measures only 2.516 (17) A, which
      is short, and we propose that the phase transition to phase III that occurs
      between 7.3 and 8.1 GPa relieves the strain that has built up in this region of
      the structure. The hydroxyl D atom now bifurcates between the OD...O contact that
      had been present in phase II and a new OD...O contact formed to a carboxylate in
      another layer. Hirshfeld surface fingerprint plots show that D...D interactions
      become more numerous, while hydrogen bonds actually begin to lengthen in the
      transition from phase II to III.

PMID- 16983164
TI  - Exploration of the high-pressure behaviour of polycyclic aromatic hydrocarbons:
      naphthalene, phenanthrene and pyrene.
AB  - The structural response of three members of the family of polycyclic aromatic
      hydrocarbons (PAHs) to high-pressure recrystallization from dichloromethane
      solutions is presented. Recrystallization of naphthalene in the 0.2-0.6 GPa
      pressure range does not result in the formation of a new polymorph. Furthermore,
      direct compression of a single crystal to 2.1 GPa does not result in a phase
      transition. A density decrease of 18.2% over the 0.0-2.1 GPa pressure range is
      observed and the principal effect of pressure is to ;tighten' the herringbone
      structural motif and decrease the size of void regions. A new polymorph of
      pyrene, form III, has been crystallized at 0.3 and at 0.5 GPa. Structural
      investigation of this new polymorph by means of topological analysis and
      comparison of Hirshfeld surfaces and fingerprint plots shows that intermolecular
      interactions are substantially different from those found in the ambient-pressure
      structures, and do not fit a previously established packing model for PAHs.
      Similar discrepancies are found for the high-pressure polymorph of phenanthrene,
      which is here re-investigated in greater detail. The structures of these high
      pressure polymorphs are dominated by pi...pi stacking with a limited contribution
      from C-H...pi (peripheral) interactions. It is perhaps not surprising that high
      pressure polymorphs deviate from a model that has been devised for ambient
      pressure structures, and this may be a direct consequence of the ability of
      pressure to modify and combine intermolecular interactions in ways that are not
      usually found at ambient pressure. This is achieved by modifying the relative
      orientations of molecules and by encouraging the formation of denser structures
      in which molecules pack together more efficiently.

PMID- 16983165
TI  - Invariom structure refinement, electrostatic potential and toxicity of 4-O
      methylalpinumisoflavone, O,O-dimethylalpinumisoflavone and 5-O-methyl-4-O-(3
      methylbut-2-en-1-yl)alpinumisoflavone.
AB  - The accurate X-ray single-crystal structures of the isoflavone compounds 4-O
      methylalpinumisoflavone, O,O-dimethylalpinumisoflavone and 5-O-methyl-4-O-(3
      methylbut-2-en-1-yl)alpinumisoflavone {alpinumisoflavone = 5-hydroxy-7-(4
      hydroxyphenyl)-2,2-dimethyl-2H,6H-benzo[1,2-b:5,4-b']dipyran-6-one} from data
      sets measured at cryogenic temperature have been obtained from invariom modelling
      using theoretically predicted Hansen and Coppens multipole-model form factors,
      which describe the aspherical electron density distribution. Molecular dipole
      moments and electrostatic potentials obtained from invariom modelling are
      discussed and compared with results from ab initio theoretical calculations. All
      three studied compounds are solvent extracts of root bark or seed powder of
      Millettia thonningii (leguminosae), a plant molluscicide and cercaricide used in
      Franco West Africa as medication against various diseases. The compounds'
      toxicities to brine shrimp have been determined and their different potencies
      tentatively related to conformation differences, intramolecular contacts, dipole
      moments and electrostatic potential features.

PMID- 16983166
TI  - pi-Bond cooperativity and anticooperativity effects in resonance-assisted
      hydrogen bonds (RAHBs).
AB  - Bond cooperativity effects, which are typical of ;resonant' chains or rings of pi
      conjugated hydrocarbons, can also occur in hydrogen-bonded systems in the form of
      sigma-bond and pi-bond cooperativity or anticooperativity. sigma-Bond
      cooperativity is associated with the long chains of O-H...O bonds in water and
      alcohols while sigma-bond anticooperativity occurs when the cooperative chain is
      interrupted by a local defect reversing the bond polarity. pi-Bond cooperativity
      is the driving force controlling resonance-assisted hydrogen bonds (RAHBs), while
      pi-bond anticooperativity has never been considered so far and is investigated
      here by studying couples of hydrogen-bonded beta-enolone and/or beta-enaminone
      six-membered rings fused through a common C=O or C-C bond. The effect is studied
      by X-ray crystal structure determination of five compounds [(2Z)-1-(2
      hydroxyphenyl)-3-phenyl-1,3-propanedione enol (1), (2Z)-1-(2-hydroxy-5
      chlorophenyl)-3-phenyl-1,3-propanedione enol (2), (2Z)-1-(2-hydroxy-5
      methylphenyl)-3-phenyl-1,3-propanedione enol (3), (2Z)-1-(2-hydroxy-4-methyl-5
      chlorophenyl)-3-phenyl-1,3-propanedione enol (4) and dimethyl(2E)-3-hydroxy-2
      {[(4-chlorophenyl)amino]carbonyl}pent-2-enedioate (5)] and by extensive analysis
      of related fragments found in the CSD (Cambridge Structural Database). It is
      shown that fusion through the C=O bond is always anticooperative and such to
      weaken the symmetric O-H...O...H-O and N-H...O...H-N bonds formed, but not the
      asymmetric O-H...O...H-N bond. Fusion through the C-C bond may produce either
      cooperative or anticooperative hydrogen bonds, the former being more stable than
      the latter and giving rise to a unique resonance-assisted ten-membered ring
      running all around the two fused six-membered rings, which can be considered a
      type of tautomerism never described before.

PMID- 16983167
TI  - Molecular versus crystal symmetry in tri-substituted triazine, benzene and
      isocyanurate derivatives.
AB  - The crystal structures of triethyl-1,3,5-triazine-2,4,6-tricarboxylate (I),
      triethyl-1,3,5-benzenetricarboxylate (II) and tris-2-hydroxyethyl isocyanurate
      (III) have been determined from conventional laboratory X-ray powder diffraction
      data using the differential evolution structure solution technique. The
      determination of these structures presented an unexpectedly wide variation in
      levels of difficulty, with only the determination of (III) being without
      complication. In the case of (I) structure solution resulted in a Rietveld
      refinement profile that was not ideal, but was subsequently rationalized by
      single-crystal diffraction as resulting from disorder. Refinement of structure
      (II) showed significant variation in side-chain conformation from the initial
      powder structure solution. Further investigation showed that the structure
      solution optimization had indeed been successful, and that preferred orientation
      had a dramatic effect on the structure-solution R-factor search surface. Despite
      the presence of identical side chains in (I) and (II), only the triazine-based
      system retains threefold molecular symmetry in the crystal structure. The lack of
      use of the heterocyclic N atom as a hydrogen-bond acceptor in this structure
      results in the formation of a similar non-centrosymmetric network to the benzene
      based structure, but with overall three-dimensional centrosymmetry. The hydrogen
      bonded layer structure of (III) is similar to that of other isocyanurate-based
      structures of this type.

PMID- 16983168
TI  - Anisotropic displacement parameters for H atoms using an ONIOM approach.
AB  - X-ray diffraction data cannot provide anisotropic displacement parameters (ADPs)
      for H atoms, a major outstanding problem in charge-density analysis of molecular
      crystals. Although neutron diffraction experiments are the preferred source of
      this information, for a variety of reasons they are possible only for a minority
      of materials of interest. To date, approximate procedures combine rigid-body
      analysis of the molecular heavy-atom skeleton, based on ADPs derived from the X
      ray data, with estimates of internal motion provided by spectroscopic data,
      analyses of neutron diffraction data on related compounds, or ab initio
      calculations on isolated molecules. Building on these efforts, an improved
      methodology is presented, incorporating information on internal vibrational
      motion from ab initio cluster calculations using the ONIOM approach implemented
      in GAUSSIAN03. The method is tested by comparing model H-atom ADPs with reference
      values, largely from neutron diffraction experiments, for a variety of molecular
      crystals: benzene, 1-methyluracil, alpha-glycine, xylitol and 2-methyl-4
      nitroaniline. The results are impressive and, as the method is based on widely
      available software, and is in principle widely applicable, it offers considerable
      promise in future charge-density studies of molecular crystals.

PMID- 16983169
TI  - New monocyclic and acyclic hNK-2 antagonists retaining the beta-turn feature. X
      ray and molecular modelling studies.
AB  - The human tachykinin NK-2 (hNK-2) receptor is considered a promising target for
      relevant pathologies at the respiratory, gastrointestinal and genitourinary
      level. With the aim of reducing the complexity of existing peptide antagonists,
      two series of hNK-2 receptor antagonists were designed, with the support of
      modelling, and synthesized. The X-ray structure determination of two compounds,
      each belonging to one of the two series, allowed the experimental validation of
      the initial rationale. In addition, it has been found that the two series share a
      beta-turn structure, a key feature for binding the hNK-2 receptor.

PMID- 16983170
TI  - Distribution of molecular pairs in Z' = 2 structures.
AB  - The positions of pairs of independent molecules in Z' = 2 structures have been
      surveyed for six of the most populated space groups for that class of structure.
      These results have been compared with the Z' = 1 situation to reveal whether
      there are any fundamental differences in the construction of the asymmetric units
      in these cases. The results indicate that, broadly speaking, the packing of the
      molecular pairs in Z' = 2 structures resembles that of single molecules in
      structures with Z' = 1; this similarity may be chiefly attributed to the
      constraints imposed by the symmetry operators of the space group. However, there
      are key differences, which are particularly marked in the space groups with
      higher symmetry, that indicate that the asymmetric units in Z' = 1 and Z' = 2
      structures are not directly comparable. In those cases where the positions of the
      pair centroids in Z' = 2 structures are similar to the positions of molecular
      centroids for Z' = 1 structures, it follows that the molecular centroids in Z' =
      2 structures must follow a different distribution. A different pattern is
      produced if the independent molecules in Z' = 2 structures behave like the
      individual molecules in Z' = 1 structures. These two scenarios combine to form
      the observed distributions of pair centroid positions.

PMID- 16983171
TI  - On hydrogen bonding in 1,6-anhydro-beta-D-glucopyranose (levoglucosan): X-ray and
      neutron diffraction and DFT study.
AB  - The geometry of hydrogen bonds in 1,6-anhydro-beta-D-glucopyranose (levoglucosan)
      is accurately determined by refinement of time-of-flight neutron single-crystal
      diffraction data. Molecules of levoglucosan are held together by a hydrogen-bond
      array formed by a combination of strong O-H...O and supporting weaker C-H...O
      bonds. These are fully and accurately detailed by the neutron diffraction study.
      The strong hydrogen bonds link molecules in finite chains, with hydroxyl O atoms
      acting as both donors and acceptors of hydroxyl H atoms. A comparison of
      molecular and solid-state DFT calculations predicts red shifts of O-H and
      associated blue shifts of C-H stretching frequencies due to the formation of
      hydrogen bonds in this system.

PMID- 16983172
TI  - Supercell and subcell description of the crystal structure of triammonium bis(O
      phospho-L-serinate) trihydrate.
AB  - The X-ray diffraction pattern obtained for a crystal of triammonium bis(O-phospho
      L-serinate) trihydrate at 100 K displays the presence of weak superstructure
      reflections with odd l indices. Omission of the superstructure reflections leads
      to orthorhombic Laue symmetry. The structure may be solved and refined in the
      space group P2(1)2(1)2(1) as an average structure omitting the weak reflections.
      The model reveals the presence of O-phospho-L-serinate monoanions, ammonium
      cations and partly disordered water molecules. The structure solution for the
      whole data set could be obtained only in the space group P2(1). There are two
      monoanions and two dianions of O-phospho-L-serinate per asymmetric unit, as well
      as six ordered ammonium cations and six water molecules.

PMID- 16983173
TI  - Accurate molecular structures and hydrogen bonding in two polymorphs of ortho
      acetamidobenzamide by single-crystal neutron diffraction.
AB  - The structures of both known forms of the polymorphic material ortho
      acetamidobenzamide, C(9)H(10)N(2)O(2), have been determined by low-temperature
      neutron single-crystal diffraction. Neutron diffraction allows the full
      description of the H-atom positions in this molecular material, which is vital in
      benchmarking related crystal-structure predictions. Significant conformational
      differences are indicated by a number of the torsion angles involving H atoms
      when compared with previous X-ray studies. A comprehensive description of the
      hydrogen-bonding scheme in both polymorphs is given.

PMID- 16983174
TI  - Isomeric N-(iodophenyl)nitrobenzamides form different three-dimensional framework
      structures.
AB  - The isomeric N-(iodophenyl)nitrobenzamides, C(13)H(9)IN(2)O(3), all form
      different three-dimensional framework structures. Molecules of N-(2-iodophenyl)-3
      nitrobenzamide (II) are linked by a combination of N-H...O and C-H...O hydrogen
      bonds and a two-centre iodo...carbonyl interaction. The supramolecular structure
      of N-(2-iodophenyl)-4-nitrobenzamide (III) is built from one N-H...O and two C
      H...O hydrogen bonds, but short I...O contacts are absent from the structure. In
      N-(3-iodophenyl)-2-nitrobenzamide (IV), which crystallizes with Z' = 2 in space
      group P2(1), the structure contains two N-H...O hydrogen bonds, four C-H...O
      hydrogen bonds, two two-centre iodo...nitro interactions and an aromatic pi...pi
      stacking interaction. The structure of N-(3-iodophenyl)-3-nitrobenzamide (V)
      contains one N-H...O hydrogen bond and three C-H...O hydrogen bonds, together
      with a two-centre iodo...nitro interaction and an aromatic pi...pi stacking
      interaction, while in N-(3-iodophenyl)-4-nitrobenzamide (VI), the combination of
      one N-H...O hydrogen bond and two C-H...O hydrogen bonds is augmented not only by
      a two-centre iodo...nitro interaction and an aromatic pi...pi stacking
      interaction, but also by a dipolar carbonyl...carbonyl interaction. In the
      supramolecular structure of N-(4-iodophenyl)-4-nitrobenzamide (IX), which
      crystallizes with Z' = 2 in space group P?overline 1, there are two N-H...O
      hydrogen bonds, four C-H...O hydrogen bonds and two three-centre iodo...nitro
      interactions.

PMID- 16983175
TI  - Order-disorder twinning model and stacking faults in alpha-NTO.
AB  - Crystals of the recently published [Bolotina, Kirschbaum & Pinkerton (2005). Acta
      Cryst. B61, 577-584] triclinic (P?overline1) structure of 5-nitro-2,4-dihydro
      1,2,4-triazol-3-one (alpha-NTO) occur as fourfold twins. There are Z' = 4
      independent molecules per asymmetric unit. We show that the structure contains
      layers with 2-periodic layer-group symmetry p2(1)/b 1 (1). This symmetry is lost
      through the stacking of the layers, which is a possible explanation for Z' = 4. A
      layer can assume four different but equivalent positions with respect to its
      nearest neighbor. Twinning arises through stacking faults and is an instructive
      example of the application of order-disorder theory using local symmetry
      operations. The near-neighbor relations between molecules remain unchanged
      through all twin boundaries. The four structures with maximum degree of order,
      one of which is the observed one, and the family reflections common to all
      domains are identified. Rods of weak diffuse scattering confirm the stacking
      model.

PMID- 16983176
TI  - Accurate bond-valence parameters for the Bi3+/Br- ion pair.
AB  - Using a new calculation scheme, reliable and physically meaningful values of the
      bond-valence parameters (r(0) = 2.567 A and b = 0.421 A) have been deduced for
      the Bi(3+)/Br(-) ion pair from the molecular geometry and from the crystal
      structure of BiBr(3).

PMID- 16983177
TI  - Primary "empty sella" in adults: endocrine findings.
AB  - Increasing evidence of impaired pituitary function in many subjects with primary
      empty sella (PES) has been reported. We conducted a retrospective analysis of our
      patients with PES, in order to ascertain presenting symptoms and endocrine status
      on diagnosis and during follow-up. Magnetic resonance imaging (MRI) of the
      pituitary leading to the diagnosis of PES was performed in 8 patients (5 F and 3
      M, age: 60.1 +/- 3.3 years, M +/- SE; group 1) after the diagnosis of global
      anterior hypopituitarism (H), and in 20 patients (F, age 56.9 +/- 2.2 years,
      group 2) for other clinical reasons. Baseline determinations of pituitary and
      target gland hormones and of IGF-I were performed. GH response to GHRH plus
      arginine stimulation was also evaluated. Ten age- and BMI-matched subjects (7 F,
      3 M, age: 53.0 +/- 4.0 years) with normal pituitary function served as controls
      (C). In group 1, the presenting symptoms leading to the diagnosis of H were
      consciousness disturbances, hyponatremia and chronic fatigue. The GH response to
      stimulation was absent (peak:1.0 +/- 0.3 ng/ml) and IGF-I levels (60.1 +/- 9.3
      ng/ml) were significantly lower (p<0.001) than in C and group 2 PES patients.
      Among group 2 PES patients, the main presenting symptoms were headache and visual
      alterations. Baseline hormone levels proved normal in 17 subjects, while slight
      hyperprolactinemia was observed in 2 and hypogonadotropic hypogonadism in one.
      The GH response to stimulation (12.9 +/- 3.4 ng/ml) and IGF-I levels (141.7 +/-
      12.0 ng/ml) were lower (p<0.05) than in C (GH: 33.4 +/- 8.8 ng/ml, IGF-I: 193.1
      +/- 20.3 ng/ml). PES is a heterogeneous condition that ranges from
      hypopituitarism to various degrees of isolated GH deficiency, and which needs
      careful endocrine assessment, treatment and follow-up.

PMID- 16983178
TI  - Effect of parathyroid hormone administration in a patient with severe
      hypoparathyroidism caused by gain-of-function mutation of calcium-sensing
      receptor.
AB  - Hypoparathyroidism caused by gain-of-function mutations of the calcium-sensing
      receptor (CaR) in the transmembrane domain is usually severe and difficult to
      manage. A patient with severe hypoparathyroidism, caused by CaR activating
      mutation F821L, was treated for 3 days (Day 1 to Day 3) with synthetic human
      parathyroid hormone 1-34 (teriparatide, PTH). An Ellsworth-Howard test of the
      patient revealed normal responses of urine phosphate and cyclic AMP excretion,
      indicating that the patient's renal tubules normally responded to extrinsic PTH.
      On Day 1 to Day 3, 0.9 microg/kg/day of PTH was administered subcutaneously twice
      daily at 0800 and 2000. On Day 1, the serum calcium level that was 1.8 mmol/l
      before PTH administration increased to 2.1 mmol/l at 1200, and gradually
      decreased to 1.8 mmol/l at 2000. On Days 2 and 3, the maximum calcium levels were
      2.5 and 2.4 mmol/l, respectively, at 1200. At 2000, they returned to or below
      basal levels at 0800. On Day 4 without PTH administration, the calcium levels
      were maintained at the basal levels at Day 0. The urine calcium/creatinine
      (Ca/Cr) ratio that was high (>0.4) before PTH injection decreased after PTH
      administration (0.4>). Changes in the ionized calcium levels were almost parallel
      with the total calcium levels. The serum inorganic phosphate (IP) level decreased
      to 2.4 mmol/l at 1000, but gradually increased before the second PTH injection to
      the level at 0800 on Day 1. The minimum IP level on Days 2 and 3 was 2.1 mmol/l
      and 2.0 mmol/l, respectively. In contrast to the remarkable changes in the serum
      calcium level by PTH treatment, the serum magnesium levels showed few changes.
      These results indicate that PTH therapy could be effective in correcting serum
      and urine calcium and the phosphate levels in hypoparathyroidism caused by
      activating mutation of CaR.

PMID- 16983179
TI  - In vitro transdifferentiation of mature hepatocytes into insulin-producing cells.
AB  - Adenovirus-mediated gene transfer of pancreatic duodenal homeobox transcription
      factor PDX-1, especially its super-active version (PDX-1/VP16), induces the
      expression of pancreatic hormones in murine liver and reverses streptozotocin
      induced hyperglycemia. Histological analyses suggest that hepatocytes are the
      major source of insulin-producing cells by PDX-1 gene transfer, although the
      conversion of cultured hepatocytes into insulin-producing cells remains to be
      elucidated. The present study was conducted to address this issue. Hepatocytes
      were isolated from adult rats. Then, PDX-1 or PDX-1/VP16 gene was introduced by
      using adenovirus vector. Two days later, the expression of insulin was detected
      at mRNA and protein levels. Transfection of PDX-1/VP16 was more efficient in
      converting hepatocytes to insulin-producing cells. Immunoreactivity of albumin
      was downregulated in transdifferentiated cells and some of them almost completely
      lost albumin expression. During the course of transdifferentiation, upregulation
      of mRNA for CK19 and alpha-fetoprotein was observed. When cultured in collagen-1
      gel sandwich configuration, hepatocytes maintained their mature phenotype and did
      not proliferate. In this condition, transfer of PDX-1/VP16 also induced the
      expression of insulin. These results clearly indicate that hepatocytes possess a
      potential to transdifferentiate into insulin-producing cells in vitro.

PMID- 16983180
TI  - Effect of methimazole treatment for 2 years on circulating IL-4, IgE, TBII, and
      TSAb in patients with hyperthyroid Graves' disease.
AB  - In this study we confirmed our previous findings on the importance of IgE in
      Graves' disease and further investigated the relationships existing among Graves'
      disease, IgE, and interleukin-4. Two hundred and thirty-two newly diagnosed
      Graves' disease patients were treated with methimazole for 2 years, and were
      classified into 3 groups according to their response to the therapy. Incidence of
      IgE elevation (IgE> or =170 IU/ml) before treatment was lowest, 23.8%, in the
      group who achieved remission without recurrence, while it was 41.7% in the group
      who achieved remission but recurrence occurred within 4 years. Incidence of IgE
      elevation before treatment was highest, 60.7%, in the group who failed to achieve
      remission, significantly higher than that of the group without recurrence.
      Incidence of IgE elevation before treatment in all these patients of Graves'
      disease were 35.3%, significantly higher than those of Hashimoto's thyroiditis
      (17.5%) and of simple goiter (7.0%). Serum IL-4 levels before treatment were
      significantly higher in the patients of Graves' disease with IgE elevation than
      in those without IgE elevation. Serum T4 concentration and TSAb titration before
      treatment were also significantly higher in elevated IgE group than in normal IgE
      group. These results support our previous findings and suggest that IL-4 may play
      important roles in the elevation of IgE, TBII, and TSAb in patients of Graves'
      disease, and that IL-4 and IgE may be involved in the development, progression,
      and maintenance of Graves' disease.

PMID- 16983181
TI  - Intracellular calcium and sodium-lithium countertransport in type 2 diabetic
      patients with and without albuminuria.
AB  - Increased intracellular calcium concentrations ([Ca(2+)](i)) and enhanced sodium
      lithium countertransport (Na/Li CT) activities may play a role in the development
      of diabetic complications such as diabetic nephropathy. The present study was
      designed to test the hypothesis that albuminuria in patients with type 2 diabetes
      is associated with increased [Ca(2+)](i) in response to stimulation with platelet
      activating factor (PAF) or with enhanced Na/Li CT activities. The study
      population comprised 203 type 2 diabetic patients. Albuminuria was defined as an
      albumin excretion rate exceeding 30 mg/d (117 cases). PAF-evoked rises in
      [Ca(2+)](i) and Na/Li CT activities were determined in Epstein-Barr-virus
      immortalized lymphoblasts. Albuminuria was related to high stimulated [Ca(2+)](i)
      but not to high basal [Ca(2+)](i). The association was independent of age, sex
      and several non-diabetes related confounders, but depended on diabetes-related
      factors, such as the duration of diabetes. The risk of albuminuria was highest in
      subjects with high [Ca(2+)](i) who reported a diabetes duration of < or =10
      years. There was no association between Na/Li CT activities and albuminuria. The
      present results support the hypothesis that albuminuria in type 2 diabetic
      patients is associated with a primary defect in intracellular calcium
      homeostasis. The association between stimulated [Ca(2+)](i) and albuminuria is
      most prominent in early diabetes.

PMID- 16983182
TI  - Effects of vertically transferred 3,3',4,4',5-pentachlorobiphenyl (PCB-126) on
      the reproductive development of female rats.
AB  - In order to study the effects of vertically transferred coplanar polychlorinated
      biphenyls on female reproductive development, female rat offspring from dams of
      Sprague-Dawley strain, which received daily oral administration of vehicle (corn
      oil) or 1 or 3 microg/kg of 3,3',4,4',5-pentachlorobiphenyl (PCB-126) from 2
      weeks prior to mating with intact males until 20 days after delivery were
      examined from birth until puberty. Hepatic expression of the aryl hydrocarbon
      receptor (AhR)-inducible enzyme cytochrome P450 1A1 (CYP1A1) was detected in all
      offspring from PCB-126-exposed dams, indicating vertical transfer of PCB-126.
      Furthermore, quantification of ovarian mRNAs encoding CYP1A1, AhR and ARNT
      demonstrated that the ovary equipped the AhR-signaling system through which
      transcription of the CYP1A1 gene was enhanced in a dose-dependent manner.
      Exposure to PCB-126 retarded the growth of offspring in both exposed groups,
      while the viability of the neonates of the exposed groups was comparable to that
      of the oil-exposed controls. The exposure to 3 mug/kg/day reduced the ovarian
      weight on postnatal day (PND) 24, with atresia of most of the antral follicles
      and delayed vaginal opening. Exposure to 1 microg/kg/day did not produce such
      effects; however, both doses of PCB-126 induced external urogenital anomalies,
      such as vaginal thread and hypospadias, in all of the PCB-126-exposed female
      offspring. These results indicate that vertically transferred PCB-126 is potent
      enough to exert a direct effect on the ovary and adversely affect female puberty
      by altering the morphological and functional development of the female
      reproductive system.

PMID- 16983183
TI  - Audiometric patterns in ototoxicity of intra-arterial Cisplatin chemoradiation in
      patients with locally advanced head and neck cancer.
AB  - This study describes audiometric patterns of ototoxicity in a consecutive series
      of patients uniformly treated with intra-arterial high-dose cisplatin
      chemoirradiation for advanced cancer of the head and neck. Air conduction
      thresholds were measured from 0.125 to 16 kHz and bone conduction thresholds were
      measured from 0.5 to 4 kHz. The overall audiometric pattern was characterized by
      maximum threshold shifts after the 2nd cisplatin infusion and a maximum total
      threshold shift at 8 kHz, irrespective of gender, age, pretreatment sensorineural
      hearing loss (SNHL) or subjective complaints during therapy. A hearing
      deterioration gradient was observed from (ultra-) high to low frequencies, worse
      with increasing pre-existent SNHL and with increasing cumulative dose of
      cisplatin chemoradiation. Cisplatin chemoradiation-induced hearing loss seemed to
      reach a plateau at higher levels (75-80 dB HL) for frequencies above 8 kHz
      compared to frequencies up to 8 kHz (45-60 dB HL). Recovery of SNHL was found
      after therapy in 27 ears characterized by extensive hearing loss at frequencies
      1, 2 and 4 kHz.

PMID- 16983184
TI  - Distortion product otoacoustic emissions as a prognostic factor for idiopathic
      sudden sensorineural hearing loss.
AB  - We investigated distortion product otoacoustic emissions (DPOAE) as a prognostic
      factor in idiopathic sudden sensorineural hearing loss (ISSHL) patients with the
      time-dependent Cox proportional-hazards model. We also compared the importance of
      the prognostic factors that are reported in the literature. 108 patients with
      ISSHL were included. Both DPOAE and pure tone audiometry were performed everyday
      for a maximum of 7 days during admission and followed every other week or monthly
      after discharge. All DPOAE amplitudes were analyzed at 2f1-f2--namely 1093, 1375,
      1750, 2187, 2781, 3500, 4375, and 5500 Hz. The average of two series of DPOAE
      intensity corrected for the noise level in eight frequencies was coded as
      dichotomous at > or =6 or <6 dB. We selected the most updated DPOAE at 3 days or
      more before the assessment of recovery into the analysis. The potential
      confounders including age, sex, history of vertigo at onset, history of
      hypertension, diabetes, coronary arterial disease, and stroke, configuration and
      severity of initial pure tone audiometry, the duration from onset to treatment,
      auditory brainstem response (ABR), vestibular evoked myogenic potential (VEMP),
      and plasma triglyceride and cholesterol levels, hemoglobin level, and erythrocyte
      sedimentation rate were collected for evaluation. The results showed that a
      better DPOAE amplitude was a significantly good prognostic indicator both in
      univariate analysis (recovery rate ratio = 3.626, 95% CI = 2.119-6.205, p <
      0.0001) and multivariate analysis (recovery rate ratio = 2.94, 95% CI = 1.537
      5.624, p = 0.0011). The Kaplan-Meier estimates showed that the younger age group
      (< or =40 years) with better initial pure tone audiometry (<65 dB) represented a
      better prognosis that was compatible with previous literature (log-rank test, p =
      0.0297 and p = 0.0019 respectively). In the univariate analysis, normal ABR and
      VEMP waveforms were associated with a better prognosis (ABR: recovery rate ratio
      = 2.984, 95% CI = 1.742-5.112, p < 0.0001; VEMP: recovery rate ratio = 1.978, 95%
      CI = 1.183-3.305, p = 0.0093). The configuration of initial audiometry was also a
      significant prognostic factor that patients with scale-out type (recovery rate
      ratio = 0.228, 95% CI = 0.089-0.584, p = 0.002) and tent type (recovery rate
      ratio = 0.081, 95% CI = 0.008-0.778, p = 0.0295) were associated with a poorer
      prognosis than those with the flat type in the multivariate analysis. In this
      study, the time-dependent Cox proportional-hazards model established the
      prognostic value of DPOAE for ISSHL patients. This model can also be used for
      comparison of different treatment protocols. In addition, the further development
      of a predictive model based on this method is worthy of being investigated.

PMID- 16983185
TI  - Behavioural and psychological symptoms of Alzheimer type dementia are not
      correlated with plasma homocysteine concentration.
AB  - BACKGROUND/AIMS: Vitamin B12 and folate deficiencies have been associated with
      cognitive impairment and various psychiatric symptoms but not specifically with
      behavioural and psychological symptoms of dementia (BPSD). A limitation of
      previous studies in dementia was lack of concurrent homocysteine measurement
      especially as it may provide a better indicator of tissue activities of these
      vitamins. This study was designed to clarify whether a relationship exists
      between plasma homocysteine concentration and BPSD. METHODS: Plasma homocysteine,
      serum vitamin B12 and folate were measured in 23 Alzheimer's disease (AD)
      patients with BPSD and 27 AD patients without BPSD as determined through the use
      of the Neuropsychiatric Inventory (NPI). Blood levels of measured substances were
      also correlated with individual NPI scores and with cumulative NPI scores for
      different cluster of symptoms. RESULTS: There was no significant difference (p =
      0.956) in the mean plasma homocysteine levels between AD patients with BPSD
      (17.48 micromol/l) and AD patients without BPSD (17.34 micromol/l). Similarly,
      there was no significant difference between the two groups in the mean serum B12
      (382.61 and 391.60 pg/ml, respectively) and folate (7.95 and 10.02 ng/ml,
      respectively). Mean levels for both vitamins were well within the laboratory
      reference range. Neither individual nor cluster NPI scores correlated
      significantly with plasma homocysteine. CONCLUSION: This study shows for the
      first time that BPSD are not associated with hyperhomocysteinaemia in Alzheimer
      dementia. Although previous studies have identified homocysteine as an
      independent risk factor in AD, the results reported here do not lend weight to an
      aetiological role for homocysteine specifically in BPSD.

PMID- 16983186
TI  - Association of insulin-like growth factor-1 receptor polymorphism in dementia.
AB  - There is an increasing interest in how oxidative stress can cause cells to go
      into apoptosis in both normal ageing and in neurodegenerative disorders. Previous
      research has implicated insulin-like growth factor-1 (IGF-1) as being involved in
      the pathogenesis in Alzheimer's disease (AD) by protecting the neurons through
      reducing neuronal susceptibility to oxidative stress. IGF-1 receptor (IGF-1R)
      polymorphisms alter cerebral and systemic levels of IGF-1 and may alter the
      function of the receptor. We genotyped the IGF-1R gene by polymerase chain
      reaction (PCR) and restriction fragment length polymorphism (RFLP) to assess
      whether this gene polymorphism can be linked to dementia. We used leukocyte DNA
      from 72 patients with AD, 75 patients with vascular dementia (VaD), 14 patients
      with mixed dementia (AD+VaD), and a control group consisting of 209 individuals
      without a history of progressive neurological disorders. Analysis of gene
      frequency for gender revealed a significant difference between female VaD
      patients and female controls carrying at least one A allele (OR = 1.8, CI 95% 1.1
      2.9, p = 0.02), but not for male patients. In addition, we found a strong
      tendency to a difference between all cases of female dementia patients and
      controls carrying the A allele (OR = 1.5, CI 95% 0.99-2.2, p = 0.054). Our
      results suggest that the A allele of IGF-1R may be involved in the pathogenesis
      of VaD in females.

PMID- 16983187
TI  - An exploratory open-label trial of ziprasidone for the treatment of behavioral
      and psychological symptoms of dementia.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of ziprasidone in behavioral
      and psychological symptoms of dementia. METHOD: A 7-week open-label trial of
      ziprasidone. RESULTS: Of the 25 patients who participated, 15 completed the
      study. The main reason for discontinuation was adverse events. The mean total
      Neuropsychiatric Inventory (NPI) score fell significantly from 47.1 +/- 17.1
      (baseline) to 25.8 +/- 17.9 (day 49) (p < 0.01). The NPI caregiver burden showed
      a significant improvement from 22.6 +/- 8.3 at baseline to 11.8 +/- 7.3. The most
      frequent adverse events were somnolence, gastrointestinal symptoms and
      parkinsonism. CONCLUSIONS: Ziprasidone was able to significantly improve
      distressing non-cognitive symptoms of dementia although adverse effects occurred.
      Additional large-scale, double-blind, well-controlled studies are necessary to
      evaluate the use of ziprasidone in this indication.

PMID- 16983188
TI  - Body mass index and mortality in elderly men and women from general population.
      The experience of Cardiovascular Study in the Elderly (CASTEL).
AB  - BACKGROUND: The role of body mass index (BMI) as a factor influencing longevity
      of the elderly subject is still under debate. OBJECTIVE: To evaluate at a
      population level whether or not BMI is a risk factor of mortality in the elderly,
      highlighting possible gender-related differences. METHODS: 3,282 Subjects aged 65
      95 years, were recruited from an Italian general population and 12-year events
      were recorded. Blood tests and anthropometric measurements were performed. BMI as
      a continuous item was divided into quintiles and, for each quintile, adjusted
      hazard ratio (HR) with 95% confidence intervals for mortality was derived by
      classes of age and gender from Cox analysis. RESULTS: BMI inversely predicted
      overall and cancer mortality in men only. Overall mortality rate was 64.7% (HR =
      1.63 [1.23-2.71]) in the 1st quintile of BMI, 54.9% (1.21 [0.92-1.73]) in the
      2nd, 54.1% (1.20 [0.85-1.67]) in the 3rd, 53.3% (1.04 [0.82-1.32]) in the 4th and
      52.5% in the 5th; cancer mortality rate was 23.1% (HR = 2.35 [1.31-4.23]), 14.2%
      (HR = 1.19 [0.65-1.80]), 15.8% (HR = 1.49 [0.93-2.39]), 15.8% (HR = 1.36 [0.84
      2.16]) and 13.4%, respectively. The relationship between BMI and mortality
      remained significant only in men aged 76 years or less. No relationship was found
      between BMI and coronary or cerebrovascular mortality. CONCLUSIONS: BMI <22.7
      kg/m2 does not improve survival in the elderly, while it is an independent
      predictor of cancer mortality in men aged <or=76 years. No prediction based on
      BMI is possible in women.

PMID- 16983189
TI  - The exocytoskeleton.
AB  - The murein or peptidoglycan wall enclosing most bacteria is essential for the
      life style of most organisms in the Domain of Bacteria. Only in special
      situations does it not play a role in the bacterial growth cycle. When life first
      appeared on this planet the cellular osmotic pressure was probably low and a
      sacculus was probably not relevant, but became necessary as bacterial life
      evolved from the complex and sophisticated cell called the Last Universal
      Ancestor. The construction of the murein wall outside of the cytoplasmic membrane
      is complex and requires elaborate special biochemistry. Growth of the sacculus in
      some parts of the surface and not in others is important for bacteria cells and
      allows them to divide and grow without becoming larger and larger and for their
      being able to maintain a shape characteristic of individual species.

PMID- 16983190
TI  - Resolving chromosome segregation in bacteria.
AB  - Bacterial chromosomes are evenly distributed between daughter cells, however no
      equivalent eukaryotic mitotic apparatus has been identified yet. Nevertheless, an
      advance in our understanding of the dynamics of the bacterial chromosome has been
      accomplished in recent years by adopting fluorescence microscopy techniques to
      visualize living bacterial cells. Here, some of the most recent studies that
      yield new insights into the nature of bacterial chromosome dynamics are
      described. In addition, we review in detail the current models that attempt to
      illuminate the mechanism of chromosome segregation in bacteria and discuss the
      possibility that a bacterial mitotic apparatus does indeed exist.

PMID- 16983192
TI  - Intermediate filament-like cytoskeleton of Caulobacter crescentus.
AB  - Eukaryotic cytoskeleton consists of three main types of filaments: actin
      microfilaments, microtubules and intermediate filaments (IFs). Actin and tubulin
      like proteins are also found in bacteria where they perform diverse cytoskeletal
      functions. IFs, however, are considered to be a characteristic constituent of
      metazoan cells only, where they (among other functions) are involved in
      determination and maintenance of cell shape and cellular integrity. Surprisingly,
      a coiled coil-rich protein called crescentin was recently shown to play a key
      role in determining the complex curved and helical cell shapes of the bacterium
      Caulobacter crescentus, and to exhibit several characteristic properties of
      animal IF proteins. First, the arrangement of the coiled coil domains of
      crescentin closely resembles the tripartite molecular architecture of IF
      proteins. Second, crescentin also possesses the defining biochemical property of
      IF proteins to assemble into 10-nm-wide filaments in vitro without cofactors.
      Furthermore, crescentin forms a higher-order helical structure in vivo, which is
      localized asymmetrically along the concave side of the cell. In close association
      with the cell membrane, the crescentin structure promotes the helical growth of
      the cell and thereby determines a curved or a helical shape, depending on the
      length of the cell. The unexpected finding of an IF-like element in a bacterium
      raises several interesting questions concerning, for example, the molecular
      mechanisms whereby complex and asymmetric cell shapes are generated by different
      bacteria, or the functional and evolutionary relatedness of crescentin to animal
      IF proteins.

PMID- 16983191
TI  - Z ring as executor of bacterial cell division.
AB  - It has become apparent that bacteria possess ancestors of the major eukaryotic
      cytoskeletal proteins. FtsZ, the ancestral homologue of tubulin, assembles into a
      cytoskeletal structure associated with cell division, designated the Z ring.
      Formation of the Z ring represents a major point of both spatial and temporal
      regulation of cell division. Here we discuss findings concerning the structure
      and the formation of the ring as well as its spatial and temporal regulation.

PMID- 16983193
TI  - Cytoskeletal cytoplasmic filament ribbon of Treponema: a member of an
      intermediate-like filament protein family.
AB  - Development of genetic systems for many bacterial genera, including Treponema,
      now allow the study of structures that are specific to certain pathogens. The
      cytoplasmic filament ribbon of treponemes that is involved in the cell division
      cycle has a unique organization. Cytoplasmic bridging proteins connect the
      filaments, maintaining the distance between them and providing the overall ribbon
      like structure. The filaments are anchored by proteins associated with the inner
      membrane. Each filament is composed of a unique monomer, the cytoplasmic filament
      protein A (CfpA), with coiled-coils secondary structures. CfpA is part of a
      growing family of proteins that we propose to call bacterial intermediate-like
      filaments (BILF).

PMID- 16983194
TI  - Archaeal flagella, bacterial flagella and type IV pili: a comparison of genes and
      posttranslational modifications.
AB  - The archaeal flagellum is a unique motility organelle. While superficially
      similar to the bacterial flagellum, several similarities have been reported
      between the archaeal flagellum and the bacterial type IV pilus system. These
      include the multiflagellin nature of the flagellar filament, N-terminal sequence
      similarities between archaeal flagellins and bacterial type IV pilins, as well as
      the presence of homologous proteins in the two systems. Recent advances in
      archaeal flagella research add to the growing list of similarities. First, the
      preflagellin peptidase that is responsible for processing the N-terminal signal
      peptide in preflagellins has been identified. The preflagellin peptidase is a
      membrane-bound enzyme topologically similar to its counterpart in the type IV
      pilus system (prepilin peptidase); the two enzymes are demonstrated to utilize
      the same catalytic mechanism. Second, it has been suggested that the archaeal
      flagellum and the bacterial type IV pilus share a similar mode of assembly. While
      bacterial flagellins and type IV pilins can be modified with O-linked glycans, N
      linked glycans have recently been reported on archaeal flagellins. This mode of
      glycosylation, as well as the observation that the archaeal flagellum lacks a
      central channel, are both consistent with the proposed assembly model. On the
      other hand, the failure to identify other genes involved in archaeal flagellation
      by homology searches likely implies a novel aspect of the archaeal flagellar
      system. These interesting features remain to be deciphered through continued
      research. Such knowledge would be invaluable to motility and protein export
      studies in the Archaea.

PMID- 16983195
TI  - Type IV pilin structures: insights on shared architecture, fiber assembly,
      receptor binding and type II secretion.
AB  - Type IV pili are long, flexible filaments that extend from the surface of Gram
      negative bacteria and are formed by the polymerization of pilin subunits. This
      review focuses on the structural information available for each pilin subclass,
      type IVa and type IVb, highlighting the contributions crystal and nuclear
      magnetic resonance structures have made in understanding pilus function and
      assembly. In addition, the type II secretion pseudopilus subunit structure and
      helical assembly is compared to that of the type IV pilus. The pilin subunits
      adopt an alphabeta-roll fold formed by the hydrophobic packing of the C-terminal
      half of a long alpha-helix against an antiparallel beta-sheet. The conserved N
      terminal half of the same alpha-helix, as well as two sequence- and structurally
      variable regions, protrude from this globular head domain. Filament models have a
      hydrophobic core formed by the signature long alpha-helices, with variable
      regions at the filament surface.

PMID- 16983196
TI  - The archaeabacterial flagellar filament: a bacterial propeller with a pilus-like
      structure.
AB  - Common prokaryotic motility modes are swimming by means of rotating internal or
      external flagellar filaments or gliding by means of retracting pili. The
      archaeabacterial flagellar filament differs significantly from the eubacterial
      flagellum: (1) Its diameter is 10-14 nm, compared to 18-24 nm for eubacterial
      flagellar filaments. (2) It has 3.3 subunits/turn of a 1.9 nm pitch left-handed
      helix compared to 5.5 subunits/turn of a 2.6 nm pitch right-handed helix for
      plain eubacterial flagellar filaments. (3) The archaeabacterial filament is
      glycosylated, which is uncommon in eubacterial flagella and is believed to be one
      of the key elements for stabilizing proteins under extreme conditions. (4) The
      amino acid composition of archaeabacterial flagellin, although highly conserved
      within the group, seems unrelated to the highly conserved eubacterial flagellins.
      On the other hand, the archaeabacterial flagellar filament shares some
      fundamental properties with type IV pili: (1) The hydrophobic N termini are
      largely homologous with the oligomerization domain of pilin. (2) The flagellin
      monomers follow a different mode of transport and assembly. They are synthesized
      as pre-flagellin and have a cleavable signal peptide, like pre-pilin and unlike
      eubacterial flagellin. (3) The archaeabacterial flagellin, like pilin, is
      glycosylated. (4) The filament lacks a central channel, consistent with
      polymerization occurring at the cell-proximal end. (5) The diameter of type IV
      pili, 6-9 nm, is closer to that of the archaeabacterial filament, 10-14 nm. A
      large body of data on the biochemistry and molecular biology of archaeabacterial
      flagella has accumulated in recent years. However, their structure and symmetry
      is only beginning to unfold. Here, we review the structure of the
      archaeabacterial flagellar filament in reference to the structures of type IV
      pili and eubacterial flagellar filaments, with which it shares structural and
      functional similarities, correspondingly.

PMID- 16983197
TI  - The flagellar cytoskeleton of the spirochetes.
AB  - The recent discoveries of prokaryotic homologs of all three major eukaryotic
      cytoskeletal proteins (actin, tubulin, intermediate filaments) have spurred a
      resurgence of activity in the field of bacterial morphology. In spirochetes,
      however, it has long been known that the flagellar filaments act as a
      cytoskeletal protein structure, contributing to their shape and conferring
      motility on this unique phylum of bacteria. Therefore, revisiting the spirochete
      cytoskeleton may lead to new paradigms for exploring general features of
      prokaryotic morphology. This review discusses the role that the periplasmic
      flagella in spirochetes play in maintaining shape and producing motility. We
      focus on four species of spirochetes: Borrelia burgdorferi, Treponema denticola,
      Treponema phagedenis and Leptonema (formerly Leptospira) illini. In spirochetes,
      the flagella reside in the periplasmic space. Rotation of the flagella in the
      above species by a flagellar motor induces changes in the cell morphology that
      drives motility. Mutants that do not produce flagella have a markedly different
      shape than wild-type cells.

PMID- 16983198
TI  - Cytoskeletal elements in bacteria Mycoplasma pneumoniae, Thermoanaerobacterium
      sp., and Escherichia coli as revealed by electron microscopy.
AB  - Recently, electron microscopic studies on the eubacteria Mycoplasma pneumoniae,
      Thermoanaerobacterium sp., and Escherichia coli have revealed the existence of
      cytoskeletal elements so far unknown in prokaryotes. The wall-less bacterium M.
      pneumoniae contains, in close vicinity to the inner face of the cytoplasmic
      membrane, a helically organized lining composed of protein elements that form a
      regular network of meshes that encloses the entire cytoplasm. Numerous regularly
      spaced pin-like structural elements, the stalks with terminal knobs, connect the
      lining with the cytoplasmic membrane. In this bacterium, a specific rod-like
      structural element is located in the tip region. Occasionally, it is bent or
      twisted. It consists of two matching blade-like sub-elements. A number of
      parallel linkers, extending from the edges of the rod, make contact with the
      lining. The proximal end of the rod is attached to a wheel-like complex. Fibrils
      originating from the wheel cross the cytoplasm and make contact with the lining.
      E. coli contains a similar helically organized lining close to the inner face of
      the cytoplasmic membrane. Groups of ribosomes (polysomes) were seen to be
      attached to the helical elements of the lining. A feature that is common to both
      bacteria and to Thermoanaerobacterium sp. appears to be that the lining and the
      fibrils crossing the cytoplasm contain a high number of copies of the bacterial
      elongation factor Tu (EF-Tu). This indicates that this protein may play an
      important role as a structural element in bacterial cytoskeletons. This notion
      was supported by experiments in which the cytoskeleton in E. coli was
      destabilized by induced expression of truncated EF-Tu, with the consequence of
      cell lysis, and by the finding that in vitro polymerization of monomeric EF-Tu
      into protofilaments was hindered in a mixture of full-size EF-Tu and truncated EF
      Tu consisting of domain 3 only. Current research and developmental efforts are
      aimed at the design of a new class of antibacterial drugs, acting by
      destabilization of the EF-Tu-containing bacterial cytoskeleton, and of an
      innovative mode of inducible lysis of recombinant bacteria by controlled
      destabilization of the EF-Tu-containing cytoskeleton.

PMID- 16983199
TI  - Mycoplasmas: a distinct cytoskeleton for wall-less bacteria.
AB  - The bacterial genus Mycoplasma includes a large number of highly genomically
      reduced species which in nature are associated with hosts either commensally or
      pathogenically. Several Mycoplasma species, including Mycoplasma pneumoniae,
      feature a multifunctional polar structure, the terminal organelle. Essential for
      colonization of the host and for gliding motility, the terminal organelle is
      associated with an internal cytoskeleton crucial to its assembly and function.
      This cytoskeleton is structurally and compositionally novel as compared with the
      cytoskeletons of other organisms, including other bacteria, is also involved in
      the cell division process. In this review we discuss the cytoskeletal structures
      and protein components of the attachment organelle and how they might interact
      and contribute to its various functions.

PMID- 16983200
TI  - Cytoskeleton of mollicutes.
AB  - Mollicutes are a class of bacteria that lack a peptidoglycan layer but have
      various cell shapes. They perform chromosome segregation and binary fission in a
      well-organized manner. Especially, species with polarized cell morphology
      duplicate their membrane protrusion at a position adjacent to the original one
      and move the new protrusion laterally to the opposite end pole before cell
      division. The featured various cell shapes of Mollicutes are supported by
      cytoskeletal structures composed of proteins. Recent progress in the study of
      cytoskeletons of walled bacteria and genome sequencing has revealed that the
      cytoskeletons of Mollicutes are not common with those of other bacteria.
      Mollicutes have special cytoskeletal proteins and structures that are sometimes
      not shared even by other mollicute species.

PMID- 16983201
TI  - The cytoskeleton of spiroplasma: a complex linear motor.
AB  - Spiroplasma are wall-less, helical bacteria from the class Mollicutes. The
      Mollicutes (Mycoplasma, Acholeplasma, Spiroplasma) evolved by regressive
      evolution to generate one of the simplest and minimal free-living and self
      replicating forms of life. The spiroplasmas are the more advanced members in the
      class and are the closest to their clostridial ancestors. Spiroplasmas were
      discovered and identified as such only in 1972 and the finding of a unique and
      well-defined internal cytoskeleton, believed to be uncommon in bacteria, followed
      in 1973. Structural analysis suggests that the core of the spiroplasmal
      cytoskeleton is a flat, monolayered ribbon comprised of the 59-kDa fib gene
      product. The ribbon follows the shortest helical line of the polar cell from end
      to end. The structural building blocks of the cytoskeletal ribbon are fibrils
      assembling into a structure with approximately 10-nm axial and lateral repeats.
      Differential length changes of the fibrils may generate a wide dynamic spectrum
      of helical and non-helical geometries allowing for directional motility in low
      Reynolds number environments. The presence of other cytoskeletal elements (FtsZ,
      FtsA, EF-TU, MreB) has been demonstrated only recently in Spiroplasma cells. The
      cellular and molecular structure and dynamics of spiroplasmas and their
      cytoskeletal elements are reviewed.

PMID- 16983202
TI  - The 'free-floating' retina epoch: new models for new scopes.

PMID- 16983222
TI  - The epidemiology and impact of traumatic brain injury: a brief overview.
AB  - Traumatic brain injury (TBI) is an important public health problem in the United
      States and worldwide. The estimated 5.3 million Americans living with TBI-related
      disability face numerous challenges in their efforts to return to a full and
      productive life. This article presents an overview of the epidemiology and impact
      of TBI.

PMID- 16983203
TI  - Effects of beta-adrenoceptors overexpression on cell survival are mediated by
      Bax/Bcl-2 pathway in rat cardiac myocytes.
AB  - BACKGROUND: Chronic activation of beta-adrenoceptors (beta-ARs) results in
      cardiac myocyte injury, even death, and diminishes the number of beta-ARs.
      OBJECTIVES: To investigate the effects of overexpression of beta(1)- or beta(2)
      AR on cardiomyocytes injured by isoprenaline (ISO). METHODS: We have used an
      adenoviral vector carrying the sequence for human beta(1)- or beta(2)-AR
      (Adv.beta(1), Adv.beta(2)) to increase the content of beta(1) or beta(2)-AR in
      isolated adult rat ventricular myocytes, and we have examined the cell survival
      and the expression of Bax and Bcl-2. RESULTS: With use of adenoviral vectors, the
      beta(1)- and beta(2)-AR contents of myocytes were increased 2.98- and 2.87-fold,
      respectively. Overexpression of beta(1)-AR sharpened the cellular injury of ISO.
      If beta(2)-AR activity was further blocked by addition of selective beta(2)-AR
      antagonist ICI118,551, the cells were more sensitive to the impairment of
      Adv.beta(1) + ISO. Overexpression of Adv.beta(2) partially inversed the
      cytotoxicity of ISO stimulation. The beneficial effects were strengthened by
      addition of CGP20712A, a beta(1)-AR-blocking agent. Western blot analysis
      demonstrated that both increasing beta(1)-AR and inhibition of beta(2)-AR
      increased the ratio of Bax/Bcl-2. Whereas, increasing beta(2)-AR and inhibition
      of beta(1)-AR decreased the ratio of Bax/ Bcl-2. Control adenovirus CGP had no
      effect on cell survival. CONCLUSIONS: Overexpression of Adv.beta(2) and/or
      inhibition of beta(1)-AR have protective effect on adult rat ventricular myocytes
      chronically stimulated by ISO. Overexpression of Adv.beta(1) and/or inhibition of
      beta(2)-AR are deleterious in the same state. The effects of beta-ARs on cell
      survival might be mediated by the Bax/Bcl-2 signal pathway.

PMID- 16983223
TI  - Traumatic brain injury research since the 1998 NIH Consensus Conference:
      accomplishments and unmet goals.
AB  - In 1998, an NIH sponsored Consensus Conference on Traumatic Brain Injury (TBI)
      Rehabilitation identified 30 different areas of needed research. A comprehensive
      review of recently generated research knowledge in the field of TBI has shown
      that a large number of Class III and IV evidence studies have been published, but
      relatively few of the more scientifically rigorous Class I or II studies. A rapid
      growth of publications on TBI rehabilitation has generated new knowledge in the
      epidemiology of TBI, the management of TBI and its secondary medical
      complications, rehabilitation of cognitive impairment, impact of TBI on community
      integration and quality of life, incidence of psychiatric dysfunction, and how
      caregivers and family members are affected. However, there is need to replicate
      many of these studies using more scientifically rigorous methodologies, while
      other areas of important TBI research remain largely unexplored.

PMID- 16983224
TI  - Multimodal neuroimaging approaches to disorders of consciousness.
AB  - Advances in neuroimaging techniques hold significant promise for improving
      understanding of disorders of consciousness arising from severe brain injuries.
      We review neuroimaging studies of the vegetative state (VS) and minimally
      conscious state (MCS), and findings in an unusual case of late emergence from
      MCS. Multimodal neuroimaging studies using positron emission tomography
      techniques, functional magnetic resonance imaging, and quantitative
      electroencephalography and magnetoencephalography quantify variations of residual
      cerebral activity across these patient populations. The results suggest models to
      distinguish the pathophysiologic basis of VS and MCS. Less clear are potential
      brain mechanisms underlying late recovery of communication in rare MCS patients.
      Diffusion tensor magnetic resonance imaging studies and recent experimental
      findings suggest that structural remodeling of the brain following severe injury
      may play a role in late functional recoveries. More generally, relatively long
      time courses of recovery following severe brain injury emphasize the need to
      develop markers for identifying patients who may harbor potential for further
      meaningful recovery. Introduction of neuroimaging into the clinical evaluation
      process will require developing frameworks for longitudinal assessments of
      cerebral function. Although limited in number, available studies already provide
      important insights into underlying brain mechanisms that may help guide
      development of such assessment strategies.

PMID- 16983226
TI  - Update on biotechnology for TBI rehabilitation: a look at the future.
AB  - The purpose of this review article is to discuss the novel dynamics in the area
      of traumatic brain injury medicine and how rapid changes in biotechnology will
      influence the lives of persons with traumatic brain injury. This article will
      focus on biomaterials, devices, cellular therapy, conventional therapy, and
      person-specific therapy that will be part of the future care plans for those who
      treat persons with traumatic brain injury.

PMID- 16983225
TI  - Military TBI during the Iraq and Afghanistan wars.
AB  - Traumatic brain injury (TBI) is an important source of morbidity in the Iraq and
      Afghanistan wars. Although penetrating brain injuries are more readily
      identified, closed brain injuries occur more commonly. Explosion or blast injury
      is the most common cause of war injuries. The contribution of the primary blast
      wave (primary blast injury) in brain injury is an area of active research.
      Lessons learned from the sports concussion and civilian mild TBI literature are
      useful. Individuals with TBI and posttraumatic stress disorder require treatment
      of both conditions. Families and communities need to be cognizant of the needs of
      these returning veterans.

PMID- 16983228
TI  - Alert senior executives to the impending storm.

PMID- 16983227
TI  - Transcranial magnetic stimulation: a possible treatment for TBI.
AB  - The purpose of this article is to outline the principles of transcranial magnetic
      stimulation (TMS), to summarize the existing use of TMS as a prognostic indicator
      and as a therapeutic device in clinical populations, and to highlight the
      potential of repetitive TMS (rTMS) as an intervention for traumatic brain injury.
      TMS is a painless method to stimulate the human brain. Repeated applications of
      TMS can influence brain plasticity and cortical reorganization through
      stimulation-induced alterations in neuronal excitability. Existing evidence has
      demonstrated positive outcomes in people with motor disorders and psychiatric
      conditions who have received rTMS as a therapeutic intervention. These findings
      suggest that rTMS may be a promising treatment for people with traumatic brain
      injury.

PMID- 16983229
TI  - Five more concepts for creating change.

PMID- 16983230
TI  - Infection prevention: tools for success.

PMID- 16983231
TI  - What's nursing's PLAN for IT ubiquity?

PMID- 16983234
TI  - Trade confusion for order.

PMID- 16983232
TI  - Sustain an infrastructure to support EBP.

PMID- 16983235
TI  - Scale down bariatric surgery's risks.

PMID- 16983237
TI  - Eliminate destructive behaviors through example and evidence.

PMID- 16983238
TI  - Best practices in wound care prevention and treatment.

PMID- 16983239
TI  - Turn new ideas into corporate visions.

PMID- 16983241
TI  - What a nurse wants, what a nurse needs.

PMID- 16983240
TI  - Improve PRN effectiveness documentation.

PMID- 16983242
TI  - Can American healthcare coverage catch up?

PMID- 16983243
TI  - A 14-year-old girl with agitation and hyperthermia.

PMID- 16983244
TI  - Prevalence of tubo-ovarian abscess in adolescents diagnosed with pelvic
      inflammatory disease in a pediatric emergency department.
AB  - OBJECTIVES: The rate of tubo-ovarian abscess (TOA) in adolescents with pelvic
      inflammatory disease (PID) is reported to range from 17% to 20%. However, no
      reports have focused specifically on the adolescent patient presenting to the
      emergency department (ED), regardless of whether they are treated in the
      inpatient or outpatient setting. Recent changes in the 2002 Centers for Disease
      Control and Prevention (CDC) Guidelines for the Treatment of Sexually Transmitted
      Diseases and sexually transmitted infection screening programs are likely to have
      impacted both the prevalence of PID and the rates of its complications,
      particularly TOA. Given that most patients with PID are treated as outpatients,
      it is imperative to accurately assess the prevalence of TOA in this population.
      Therefore, we sought to determine the rate of TOA in female adolescents diagnosed
      with PID in a large urban pediatric ED. METHODS: We performed a retrospective
      medical record review to assess the prevalence of TOA in adolescents diagnosed
      with PID in the ED by an attending physician in pediatric emergency medicine. All
      cases were identified on the basis of the clinical criteria from the 2002 CDC
      Guidelines for the Treatment of Sexually Transmitted Diseases. Data collected
      included historical and physical examination findings, and laboratory and
      radiological imaging results. RESULTS: Three (2.4%; 95% confidence interval, 0.5
      6.7) of 127 patients diagnosed with PID in the ED who had imaging or clinical
      follow-up were also found to have a TOA. The mean age of the patients was 16
      years. Most patients (89%) had imaging studies performed within 24 hours; most of
      these studies (97%) were pelvic ultrasounds. Eleven patients did not have imaging
      but had clinical follow-up within 72 hours. Four patients were diagnosed with PID
      during the study period and were lost to follow-up. CONCLUSION: The rate of TOA
      in adolescents diagnosed with PID in an urban pediatric ED is much lower than the
      rates previously reported in adolescents. This lower prevalence may be attributed
      to the broader 2002 CDC guidelines for diagnosing PID. In addition, community
      based screening programs for Chlamydia trachomatis and Neisseria gonorrhoeae may
      help to identify young women at risk for developing PID earlier in the course of
      infection.

PMID- 16983245
TI  - Odds of critical injuries in unrestrained pediatric victims of motor vehicle
      collision.
AB  - OBJECTIVES: To compare morbidity and mortality between pediatric victims of motor
      vehicle collisions (MVC) who were unrestrained to those restrained and to
      describe compliance with child restraint usage in our population. MATERIALS AND
      METHODS: A retrospective consecutive chart review study was performed on MVC
      victims 14 years old and younger who presented to our academic, level 1 trauma
      emergency department in 2003. Each patient's emergency department and hospital
      course was reviewed and data were collected. Odds ratios (ORs) were calculated
      for unrestrained children with respect to restrained children for fractures;
      intraabdominal injuries, intrathoracic injuries, intracranial injuries,
      admission, surgery, blood transfusion, intubation; and deaths. Hospital charges
      and length of hospital stay were compared between those unrestrained and
      restrained. Percentage of children unrestrained was determined. RESULTS: Of 336
      patients, 81 (24%) were unrestrained. Mean hospital stay for unrestrained
      children was longer, 1.94 days (95% confidence interval [CI] 0.75-3.12) versus
      0.098 days (95% CI 0.02-0.21). Unrestrained victims had higher mean charges,
      14,754 dollars (95% CI 7676 dollars-21,831 dollars) versus 1996 dollars (95% CI
      1207 dollars-2786 dollars). Admissions (OR = 14.48, 95% CI 5.91-38.63), fractures
      (OR = 5.85, 95% CI 2.13-16.89), intraabdominal injuries (OR = 20.16, 95% CI 2.36
      930.68), and intrathoracic injuries (OR = 13.09, 95% CI 1.26-647.05) were all
      more likely in unrestrained patients. No restrained child had intracranial
      injury, whereas 9/81 (11.11%) of unrestrained did. Odds were higher in
      unrestrained for surgery [OR = 13.09, 95% CI 3.30-74.33] and transfusion [OR =
      27.61, 95% CI 3.56-229.85]. Ten out of 81 (12.35%) of unrestrained children
      required intubation versus none for restrained. The only 2 mortalities were
      unrestrained patients. CONCLUSION: Critical injuries and cost of care are higher
      in unrestrained than restrained children. Improved compliance with child safety
      restraint in southern Arizona should decrease childhood morbidity and mortality
      from MVCs.

PMID- 16983246
TI  - Foreign body removal from the external auditory canal in a pediatric emergency
      department.
AB  - OBJECTIVES: To describe the experience with external auditory canal foreign body
      removal in a pediatric emergency department. To identify factors associated with
      procedural complications and/or failed removal. METHODS: Retrospective case
      series of patients treated in the emergency department over a 5-year period.
      Primary outcomes include success and complication rates. Secondary outcomes
      include removal rates in the otolaryngology clinic and operating room. RESULTS:
      Physicians in our pediatric emergency department successfully removed 204 (80%)
      of 254 foreign bodies. In 30 cases (12%), there was a complication. Multiple
      attempts at removal were associated with failure (relative risk [RR], 6.0; 95%
      confidence interval [CI], 3.0-12.0) and complications (RR, 3.1; 95% CI, 1.5-6.3).
      The use of multiple instruments was also associated with failure (RR, 5.4; 95%
      CI, 2.7-10.8) and complications (RR, 4.0; 95% CI, 2.0-7.6). Of the 244 patients
      in whom emergency department attempts at removal were made, 26 were successfully
      removed in otolaryngology clinic, and 14 were removed in the operating room.
      Foreign bodies present in the canal for more than 24 hours were not at higher
      risk of failed removal or complications. Patients younger than 4 years also were
      not at increased risk of having failed removal or complications. CONCLUSIONS:
      Physicians in a pediatric emergency department remove most foreign bodies from
      the external auditory canal successfully with minimal complications and need for
      operative removal. These data suggest that referral to otolaryngology be
      considered if more than 1 attempt or instrument is needed for removal.

PMID- 16983247
TI  - Methods of categorizing emergency department visit urgency: a survey of pediatric
      emergency medicine physicians.
AB  - OBJECTIVE: Between 20% and 80% of emergency department (ED) visits are nonurgent.
      This variability in estimates is partially due to the multiple classification
      methods used, none of which has undergone validity or reliability testing. Our
      objectives were to determine the methods thought to be most valid and to
      understand expert perceptions of nonurgent ED utilization. METHODS: A survey of
      the Pediatric Emergency Medicine (PEM) Special Interest Group at the 2005
      Pediatric Academic Societies meeting was conducted. An education session with
      case-based discussion for categorizing ED visit urgency was presented. Six
      methods were reviewed: implicit criteria, explicit criteria, resource
      utilization, diagnoses, Current Procedural Terminology Codes, and nurse triage
      category. The primary outcome was the percentage of respondents ranking each
      method first or second best for categorizing urgency. Respondents also identified
      ED resources and presenting symptoms constituting an urgent visit. RESULTS:
      Seventy-four percent of attendees completed the survey, most were Pediatric
      Emergency Medicine physicians. Implicit criteria were rated highest, with 65.1%
      ranking it first or second, followed by explicit criteria (53.8%). With limited
      data available, resource utilization ranked highest (68.6%), followed by nurse
      triage (61.2%). There was an agreement that certain presenting symptoms and
      resources were adequate for determining ED visit urgency; however, there was no
      agreement on whether x-rays, urinalyses, or fever in a child older than 3 months
      was sufficient to identify urgency. CONCLUSIONS: Methods using complete medical
      record information are favored to determine ED visit urgency. Resource
      utilization and nurse triage are preferred when limited data are available. This
      survey will serve as the basis for endorsement of methodologically sound criteria
      for ED visit urgency.

PMID- 16983248
TI  - Language and length of stay in the pediatric emergency department.
AB  - BACKGROUND: Quality and accessibility of care for patients presenting to the
      emergency department (ED) can be limited if they cannot communicate in the same
      language as their health care provider. STUDY OBJECTIVES: We aimed to determine
      if children whose parents speak a primary language other than English have a
      longer length of stay (LOS) in the ED compared with English-speaking families.
      METHODS: We reviewed computerized ED records of age-matched English and 4 most
      common non-English languages in a tertiary pediatric hospital in Toronto, Canada.
      We randomly chose English-speaking families in a 3:1 ratio with non-English. We
      performed bivariate analyses and a multivariable linear regression to test the
      relationship between language, triage score, age, gender, day of the week, and
      diagnostic grouping. RESULTS: Out of 48,497 visits for 1 year, we included 6051
      English-, 628 Spanish-, 486 Cantonese-, 486 Mandarin-, and 417 Tamil-speaking
      families. The average LOS was 3.86 and 3.95 hours for English and non-English
      speaking patients, respectively (P > 0.05). Non-English speakers had lower acuity
      more frequently (P = 0.004) and arrived more over weekdays (P = 0.02). In the
      multivariate regression model, language, triage score, age, and gender were all
      significantly associated with LOS. Only 6% of the variance in LOS was explained
      by the regression model. CONCLUSIONS: Language, triage score, patient age, and
      gender are significantly associated with LOS in the ED. Among other
      interventions, securing ways to accommodate non-English-speaking health providers
      in the ED can possibly shorten the LOS and reduce nonacute visits to the ED.

PMID- 16983249
TI  - Trampoline-related injury in children.
AB  - OBJECTIVES: To quantify and describe trampoline-related injuries in children
      attending an urban pediatric emergency department. METHODS: Retrospective cohort
      study of consecutive patients attending a children's emergency department with
      trampoline-related injuries over a 3-month period (May-July 2005). RESULTS: One
      hundred and sixty-eight children were treated for trampoline-related injuries
      during the period reviewed. Sixty-three percent were girls. Their age ranged
      between 4 months and 16 years (mean, 10.4 years [SD, 3 years and 10 months]).
      Lower limb injuries (51%) were more common overall. The most common injuries were
      to the ankle (31%), followed by foot (9.2%), and neck (8.4%). Sprain or soft
      tissue injuries (68%) were the most common type of injury, followed by fracture
      (12.2%). The most common mechanism of injury was inversion of the ankle on a
      trampoline (18.4%). CONCLUSIONS: Trampoline-related injuries represented 2.5% of
      morbidity from accidental trauma in children presenting to emergency department
      in our study. The rate and severity of injury has become a significant public
      health concern. It appears that current preventative strategies are inadequate in
      making children's carers aware of the potential risks of trampoline use,
      particularly when used recreationally.

PMID- 16983250
TI  - Fell on outstretched hand.
AB  - Radial neck fractures in children are not uncommon. Most are minimally displaced
      or nondisplaced. Severely displaced fractures or angulated radial neck fractures
      in children often have poor outcomes, especially if not reduced, and even after
      open reduction.

PMID- 16983251
TI  - Acute abdominal pain caused by a spontaneous intramyometrial hematoma in type III
      von Willebrand disease.
AB  - OBJECTIVES: To discuss the clinical picture, differential diagnosis and
      management of a pediatric patient with von Willebrand disease (vWD) presenting
      with severe abdominal pain caused by an intramyometrial hematoma. METHODS: A 17
      year-old girl with type III vWD was admitted to the emergency department with a
      complaint of severe lower abdominal pain different from her usual dysmenorrhea.
      She had no history of trauma to the pelvic region or any sexual intercourse.
      Transabdominal ultrasonography and magnetic resonance imaging revealed an
      intramyometrial hematoma in anterofundal region of uterus. RESULTS: A favorable
      clinical outcome was obtained through a treatment with factor VIII concentrates
      containing von Willebrand factor which resulted in complete resolution of the
      sonographic findings within 3 weeks. CONCLUSIONS: Intramyometrial hematoma can be
      an unusual cause of severe abdominal pain in patients with vWD applying to
      emergency departments. Especially in adolescence years, when transvaginal
      sonography could not be performed, transabdominal ultrasonography and magnetic
      resonance imaging are useful tools for the diagnosis.

PMID- 16983252
TI  - Duodenal hematoma after upper endoscopy and biopsy in a 4-year-old girl.
AB  - We describe a 4-year-old girl who developed a duodenal hematoma after upper
      endoscopy and biopsy. Although rare, duodenal hematoma formation can occur after
      upper endoscopy and biopsy in otherwise healthy children. A young child
      presenting with a duodenal hematoma in the absence of a clear mechanism of either
      previous gastrointestinal procedures or injury to the abdomen should have an
      extensive evaluation to exclude child abuse. A thorough evaluation for other
      medical causes, such as a coagulopathy, should be performed simultaneously.

PMID- 16983253
TI  - Munchausen syndrome by proxy caused by ipecac poisoning.
AB  - OBJECTIVE: To present a case of Munchausen syndrome by proxy caused by ipecac
      poisoning to increase the awareness of their warning signs and symptoms so that
      they may be recognized and diagnosed earlier. CASE: Report of one case of a child
      who was determined to be a victim of Munchausen syndrome by proxy by ipecac
      poisoning who was hospitalized multiple times over a 4-year period at 2 different
      hospitals before an accurate diagnosis was made.

PMID- 16983254
TI  - Playing soccer; fell; pain in the hip.

PMID- 16983255
TI  - ECGs in the ED.

PMID- 16983256
TI  - Emergency preparedness for pandemic influenza.

PMID- 16983257
TI  - Pediatric emergency medicine: legal briefs.

PMID- 16983264
TI  - Benchmark for intensive care unit length of stay: One step forward, several more
      to go.

PMID- 16983265
TI  - Does weaning postpone liberation?

PMID- 16983266
TI  - A new twist on albumin therapy in the intensive care unit, again.

PMID- 16983267
TI  - Dismantling the barriers to optimal end-of-life care in the intensive care unit.

PMID- 16983268
TI  - Blowing up the lungs--Does the right ventricle care?

PMID- 16983269
TI  - Soluble CD163: An age-dependent, anti-inflammatory biomarker predicting outcome
      in sepsis.

PMID- 16983270
TI  - A new perspective on community consultation in pediatric resuscitation research.

PMID- 16983271
TI  - Healthcare-associated bacteremia: Stirring the mud.

PMID- 16983272
TI  - Let's go dynamic with procalcitonin!

PMID- 16983273
TI  - Left atrial decompression: Is there a standard during extracorporeal support of
      the failing heart?

PMID- 16983274
TI  - Interleukin-6: Still crazy after all these years.

PMID- 16983275
TI  - Does cold-bloodedness protect against sepsis?

PMID- 16983276
TI  - Evolving career of hyperbaric oxygen in sepsis: From augmentation of oxygen
      delivery to the modulation of the immune response.

PMID- 16983277
TI  - Intraperitoneal microdialysis: Postoperative monitoring of splanchnic ischemia by
      measurements of the lactate pyruvate ratio.

PMID- 16983278
TI  - To drink or not to drink: The role of fluid versus vasopressor resuscitation in
      traumatic brain injury and systemic inflammatory response syndrome.

PMID- 16983280
TI  - Effect of life-support decision tools on actual decisions in the intensive care
      unit.

PMID- 16983282
TI  - Dobutamine to rescue the microcirculation?

PMID- 16983284
TI  - Diagnosing pulmonary embolism in pregnancy: Is there a role for D-dimer as a
      stand-alone test?

PMID- 16983285
TI  - Pediatric in--intensive-care-unit cardiac arrest: New horizon of extracorporeal
      life support.

PMID- 16983286
TI  - Severe acute respiratory distress syndrome, leptospirosis, and lung protective
      strategies.

PMID- 16983290
TI  - Traumatic perforation of tympanic membrane by cotton tipped applicator.

PMID- 16983291
TI  - Gunshot wound to the femoral neck: a unique case.

PMID- 16983292
TI  - Blunt vertebral artery injury leading to cervical fracture diagnosis.

PMID- 16983293
TI  - Osteoporotic pelvic insufficiency fracture with gross instability.

PMID- 16983294
TI  - Acute exertional compartment syndrome of the forearm.

PMID- 16983295
TI  - Fulminant pulmonary embolism treated by extracorporeal membrane oxygenation in a
      patient with traumatic brain injury.

PMID- 16983296
TI  - Retroperitoneal gunshot wound hernia: an unusual cause of early postoperative
      small bowel obstruction after laparotomy for trauma.

PMID- 16983298
TI  - Surgical management of Ehlers-Danlos syndrome type IV following abdominal trauma.

PMID- 16983297
TI  - Penetrating craniofacial injury inflicted by a knife.

PMID- 16983299
TI  - Perforated Meckel's diverticulum in a child after blunt abdominal trauma.

PMID- 16983300
TI  - Isolated cerebral fat emboli syndrome in multiply injured patients: a review of
      three cases and the literature.

PMID- 16983301
TI  - Hybrid procedures combining open and endovascular surgical techniques for the
      management of subclavian artery injuries.

PMID- 16983302
TI  - Pediatric tracheal disruption repaired via median sternotomy.

PMID- 16983303
TI  - Prognosis following severe head injury: Development and validation of a model for
      prediction of death, disability, and functional recovery.
AB  - BACKGROUND: A prognostic model for head trauma patients is useful only if it
      predicts clinically relevant outcomes accurately on new subjects in various
      settings. Most existing models consider only dichotomous outcome and have not
      been tested externally. We developed and validated a rule for prediction of three
      functional outcome states after severe head injury, using information from day 1.
      METHODS: The model was developed in a cohort of 304 adults who were admitted to a
      Dutch trauma center and had survived and remained comatose for >24 hours
      following severe head injury. We used ordinal logistic regression analysis to
      predict the extended Glasgow Outcome Scale after > or =12 months, merged into
      three categories. We preselected five known predictors of outcome and used
      bootstrapping techniques to avoid statistical overfitting. The performance of the
      model was subsequently tested in a cohort of 122 patients from an unrelated
      hospital. RESULTS: The model contained age (p < 0.0001), best motor response on
      day 1 (p = 0.002), pupil response after resuscitation (p = 0.005), computed
      tomography findings (p = 0.004), and presence of arterial hypotension (p = 0.37)
      as predictor variables. In the external validation cohort, the model showed
      adequate agreement between observed and predicted outcome probabilities
      (calibration). The model had a good ability to discriminate patients with
      different outcomes (c-statistic 0.808). The predictive accuracy was 66% when the
      model was used to classify patients across the three outcome categories.
      CONCLUSIONS: We have developed a practical model for predicting the probability
      of death, survival with major disability, and functional recovery in patients who
      are comatose 24 hours after severe head injury. The model performed well in an
      external setting, indicating that measures to avoid statistical overfitting were
      successful.

PMID- 16983304
TI  - Hepatic vascular isolation in treatment of a complex hepatic vein injury.

PMID- 16983306
TI  - Hearing loss in chronic lymphocytic leukemia.

PMID- 16983305
TI  - Tourniquet cuff pressure: The gulf between science and practice.
AB  - Tourniquet use is effective in producing a bloodless field. It is recommended
      that the least effective pressures be used to minimize tissue microstructure and
      biochemical damage from tourniquet application. When applied at the thigh, the
      minimum effective tourniquet pressure is 90 to 100 mm Hg above systolic BP, and
      in a normotensive, nonobese patient, pressure of 250 mm Hg is sufficient.
      Similarly, an arm tourniquet pressure of 200 mm Hg is recommended. The purpose of
      this survey was to assess the tourniquet pressures used by orthopaedic surgeons,
      both academic and community based, and their familiarity with associated
      literature. MATERIALS: A Website-based survey was distributed to a random sample
      of academic and community-based surgeons. Respondents were asked the upper and
      lower-extremity tourniquet pressures they routinely use. They were asked if they
      were able to cite or were aware of literature to support their answer. They were
      also asked to specify their practice setting and years in practice. Results were
      statistically analyzed utilizing Fisher's exact test and Mann-Whitney test.
      RESULTS: A total of 199 survey responses were collected. Out of these, 151 (76%)
      were complete for the lower extremity, and 141 (71%) were complete for upper
      extremity. The average years in practice were 12.6 years (range, 1-30). The
      median LE pressure was 300 mm (range, 150-400), and the median UE pressure was
      250 mm (range, 150-300). Less than 20% of respondents routinely used pressures of
      250 mm or less for the lower extremity. For upper extremity, only 11.3% used
      pressures at or below 200 mm. Surgeons in academic practice were more likely to
      use lower tourniquet pressures, and less likely to choose "don't know" as the
      option for literature support, but the difference was not statistically
      significant. Although 60% of respondents thought that they were aware of
      literature supporting their answers, only 25% of these for the lower extremity
      and 11% for the upper used the correct pressures. CONCLUSION: This survey
      demonstrates the existing gulf between tourniquet use and supporting literature.
      Tourniquet use is not benign and the correct pressure usage allows the least
      morbidity. We hope this survey will raise awareness of the correct tourniquet
      pressures and change practice patterns based on "that's how we have always done
      it".

PMID- 16983307
TI  - Malleus head fixation with stapedial otosclerosis.

PMID- 16983308
TI  - Cavernous hemangioma of the endolymphatic sac.

PMID- 16983309
TI  - Paget's disease of the temporal bone.

PMID- 16983310
TI  - Jacobson's nerve schwannoma.

PMID- 16983312
TI  - Dehiscence of posterior semicircular canal.

PMID- 16983314
TI  - Recurrent diving-related inner ear barotrauma.
AB  - OBJECTIVE: To present two cases of recurrent diving-related inner ear barotrauma
      (IEB) and to discuss the possible cause and pathogenesis of the increased inner
      ear vulnerability. STUDY DESIGN: Case series. SETTING: Tertiary referral center.
      PATIENTS: Two scuba divers suffering from repeated cochleovestibular barotrauma.
      INTERVENTIONS: Neurotological evaluation, perilymphatic fistulae repair, and
      conservative treatment. MAIN OUTCOME MEASURE: The increasing popularity of scuba
      diving expose the individuals involved in this sport to unique pathologies that
      are not common under terrestrial conditions. The otolaryngologist who is involved
      in the care of these patients is required to diagnose and treat diving-related
      ear injuries and to consider the risk for recurrent inner ear injury when diving
      is resumed. CONCLUSION: IEB carries a risk for permanent hearing loss and chronic
      vestibulopathy. We recommend complete neurotological evaluation including high
      resolution CT of the temporal bones as a routine workup for IEB. The presence of
      a significant residual sensorineural hearing loss, evidence for noncompensated
      vestibular damage, and CT findings of possible enhanced cerebrospinal fluid
      perilymph connection should be considered when a return to diving activity is
      considered.

PMID- 16983313
TI  - Optimization of ribonucleic acid detection from archival Guinea pig temporal bone
      specimens.
AB  - HYPOTHESIS: The choice of ribonucleic acid (RNA) isolation protocol coupled with
      modifications to RNA extraction and detection procedures may result in a more
      reliable method to detect gene expression in archived temporal bones. BACKGROUND:
      A large number of archival temporal bones exist. Retrospective analysis of these
      specimens using techniques of RNA extraction will greatly enrich our
      understanding of the pathophysiology of specific otologic diseases. However,
      archival human temporal bones are aged and embedded in paraffin or celloidin,
      rendering isolation and manipulation of nucleic acid in preserved specimens
      difficult, especially as it pertains to RNA degradation. Despite some reports of
      moderate success in the recent past, RNA isolation and gene expression using
      polymerase chain reaction (PCR) analysis continues to be challenging and
      unreliable. Archival guinea pig temporal bone specimens were used to develop and
      optimize a protocol for RNA extraction and gene expression analysis using PCR and
      quantitative PCR methods. The genes amplified comprise housekeeping genes and
      genes associated with the glutamate pathway. METHODS: Archival celloidin-embedded
      guinea pig temporal bones were collected from the senior author's collection of
      experimental hydropic inner ear specimens. RNA from this tissue was extracted
      using the protocol described previously in 16animals and using a modified trizol
      extraction technique in 10 animals. Gene expression analysis was performed on the
      extracted RNA. Analysis included two housekeeping genes, GAPDH and 18S, as well
      as three mediators of the glutamate pathway, glutamate aspartate transporter,
      glutamate synthetase, and inducible nitric oxide synthase. RESULTS: Compared with
      the standard extraction protocol, the trizol-based extraction technique showed
      greater reliability and reproducibility of RNA detection. The housekeeping gene
      GAPDH or 18S was detected in 7 of 36 attempts with the standard protocol versus 9
      of 9 using the modified extraction method (P < 0.001). The gene of interest,
      glutamate aspartate transporter, was detected in 3 of 26 attempts with the
      standard protocol versus 12 of 13 attempts using the modified extraction method
      (P < 0.001). Quantification of messenger RNA levels was then achieved using
      quantitative PCR methods. CONCLUSION: Improved reliability for detection of gene
      expression and demonstration of reproducibility were accomplished by modification
      of RNA extraction technique and standard reverse transcriptase PCR protocol. In
      addition, we also showed that gene expression from archival material can be
      quantified by real-time PCR.

PMID- 16983315
TI  - DNA methylation of multiple genes in vestibular schwannoma: Relationship with
      clinical and radiological findings.
AB  - HYPOTHESIS: The purpose of this study was to examine the DNA methylation profile
      of several genes in a series of vestibular schwannomas, and to analyze its
      relationship with clinical and radiological features. BACKGROUND: Aberrant
      methylation of promoter regions is a major mechanism for silencing of tumor
      suppressor genes in several tumors. There is limited information about
      methylation status in vestibular schwannoma, with no clinical or radiological
      implications described to date. METHODS: The methylation status of 16 tumor
      related genes including RASSF1A, RAR-B, VHL, PTEN, HMLH1, RB1, TP16, CASP8, ER,
      TIMP3, MGMT, DAPK, TP73, GSTP1, TP14, and THBS1 was examined in a series of 22
      vestibular schwannomas.The bisulfite modification of genomic DNA was performed.
      Clinical and radiological features were compared with the methylation results.
      RESULTS: Methylation values from 9% to 27% were found in 12 of 16 genes tested,
      including RASSF1A, VHL, PTEN, TP16, CASP8, TIMP3, MGMT, DAPK, THBS1, HMLH1, TP73,
      and GSTP1. A significant association was found between CASP8 and RASSF1A
      methylation. Methylation of CASP8 was associated with the patient's age and the
      tumor size. Methylation of TP73 was associated with hearing loss. RASSF1A
      methylation was inversely correlated with the clinical growth index. CONCLUSION:
      Aberrant methylation of tumor-related genes may play a role in the development of
      vestibular schwannomas. Our results may provide useful clues to the development
      of prognostic assays for these tumors.

PMID- 16983316
TI  - Comparative study of laser versus radiofrequency myringotomy in rabbits: The
      effectiveness of mitomycin C application.
AB  - OBJECTIVE: To compare laser-assisted tympanostomy (LAT) with radiofrequency
      myringotomy (RFM), as well as the effectiveness of mitomycin C (MC) on the above
      techniques, in rabbits. STUDY DESIGN: Experimental animal research protocol.
      SETTING: University of Crete, School of Medicine, Medical Experimental Education
      and Research Center. METHODS: Bilateral myringotomies were performed under
      general anesthesia on 40 rabbits. LAT was performed on 20 animals (40 ears) and
      RFM on the remaining 20 animals (40 ears). MC (0.3 mg/mL) pledgets were applied
      to the right ears and saline pledgets to the left ears. Animals were monitored
      weekly using otomicroscopy until myringotomy closure. Kaplan-Meier survival
      techniques were used to compare myringotomy patency times. INTERVENTIONS: Under
      general anesthesia, bilateral LAT was performed on 20 rabbits and bilateral RFM
      on 20 rabbits. MAIN OUTCOME MEASURES: Myringotomy patency time. RESULTS: The mean
      patency times of the saline-treated ears were: 1.85 weeks (95% confidence
      interval [CI], 1.556-2.144 wk) for the LAT group and 1.70 weeks (95% CI, 1.494
      1.906 wk) for the RFM group. This difference was not significant (p > 0.5). MC
      application significantly prolonged mean patency time (p < 0.0001) in both LAT
      and RFM groups. The mean patency times in the MC-treated ears were 5.45 weeks
      (95% CI, 5.226-5.674 wk) for the LAT group and 5.55 weeks (95% CI, 5.285-5.815
      wk) for the RFM group. This difference was not significant (p > 0.5). CONCLUSION:
      There is no significant difference in myringotomy patency times between LAT and
      RFM techniques in rabbits, whereas MC significantly prolongs the patency rate of
      either technique.

PMID- 16983322
TI  - Isotretinoin revisited: pluripotent effects on human sebaceous gland cells.
AB  - Nelson et al. confirmed the previously described antiproliferative effect of
      isotretinoin on human sebocytes. They attributed a portion of this decrease to
      cell cycle arrest and detected sebocyte apoptosis, which was not recapitulated by
      alitretinoin or tretinoin. These events were specific to sebocytes, as
      isotretinoin failed to induce apoptosis in keratinocytes. Isotretinoin-induced
      apoptosis was shown to be an RAR-independent mechanism.

PMID- 16983323
TI  - Photoadaptation: a path toward rational phototherapy protocols.
AB  - Photoadaptation is defined as the diminished future response to equivalent doses
      of irradiation. It is most often estimated in vivo by looking at changes in the
      minimal erythema dose with subsequent doses of UV radiation. Although
      photoadaptation's mechanism of action is poorly understood, Palmer et al. help
      clarify the clinical significance of photoadaptation for the dosimetry of UV
      based phototherapy.

PMID- 16983324
TI  - Sebaceous skin lesions as clues to hereditary non-polyposis colorectal cancer.
AB  - Cutaneous lesions consonant with Muir-Torre syndrome strongly suggest hereditary
      non-polyposis colorectal cancer (HNPCC). Ponti et al. discuss the importance of
      combining molecular genetic features of the sebaceous neoplasms, including
      microsatellite instability and immunohistochemistry, with family history, to
      determine the likelihood of HNPCC. Proof of diagnosis is identification of one of
      the mismatch repair germline mutations.

PMID- 16983325
TI  - The duality of angiogenesis: implications for therapy of human disease.
AB  - Angiogenesis, the development of a microvasculature to a neoplastic,
      inflammatory, or infectious disease process, is a promising therapeutic target
      for disease therapy that has not been fully exploited. To further understand
      angiogenesis and its potential for therapy of dermatologic disorders, one must
      understand the many dualities of pathologic angiogenesis. These dualities are
      direct versus indirect angiogenesis inhibition, the differing origins of
      endothelial cells, which may arise either locally or through bone marrow stem
      cells, and regulation of vascular endothelial growth factor (VEGF) by hypoxia
      dependent and/or independent pathways. The future development of therapy directed
      at pathologic angiogenesis is dependent upon an understanding of the factors that
      regulate angiogenesis. The presence of both direct and indirect inhibition of
      angiogenesis, the multiple sources of endothelial cells, and the regulation of
      VEGF by hypoxia-independent and/or-dependent pathways must taken into
      consideration if the promise of effective therapy of human disease is to be
      realized.

PMID- 16983326
TI  - New insights into the molecular control of the lymphatic vascular system and its
      role in disease.
AB  - The cutaneous lymphatic system plays an important role in the maintenance of
      tissue fluid homeostasis, in the afferent phase of the immune response, and in
      the metastatic spread of skin cancers. However, the lymphatic system has not
      received as much scientific attention as the blood vascular system, largely due
      to a lack of lymphatic-specific markers and to the dearth of knowledge about the
      molecular regulation of its development and function. The recent identification
      of genes that specifically control lymphatic development and the growth of
      lymphatic vessels (lymphangiogenesis), together with the discovery of new
      lymphatic endothelium-specific markers, have now provided new insights into the
      molecular mechanisms that control lymphatic growth and function. Moreover,
      studies of several genetic mouse models have set the framework for a new
      molecular model for embryonic lymphatic vascular development, and have identified
      molecular pathways whose mutational inactivation leads to human diseases
      associated with lymphedema. These scientific advances have also provided
      surprising evidence that malignant tumors can directly promote lymphangiogenesis
      and lymphatic metastasis, and that lymphatic vessels play a major role in
      cutaneous inflammation and in the cutaneous response to UVB irradiation.

PMID- 16983328
TI  - Bioinformatics approach leads to the discovery of the TMPRSS2:ETS gene fusion in
      prostate cancer.
AB  - Recurrent chromosomal rearrangements have not been well characterized in common
      carcinomas. We describe the use of a novel bioinformatics approach to discover
      candidate oncogenic chromosomal aberrations on the basis of outlier gene
      expression called COPA (cancer outlier profile analysis). We demonstrate how this
      approach led to the identification of gene fusions of the 5'-untranslated region
      of TMPRSS2 (21q22.3), an androgen regulated gene, with the ETS transcription
      factor family members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4(17q21). These
      novel gene fusions suggest a mechanism for overexpression of the ETS genes in the
      majority of prostate cancers identified through PSA screening. Considering the
      high incidence of prostate cancer and the high frequency of this gene fusion, the
      TMPRSS2-ETS gene fusions are the most common genetic aberration so far described
      in human malignancies. The clinical implications of this discovery are
      significant for diagnosis and potentially for the development of targeted
      therapy.

PMID- 16983329
TI  - Agrin, a novel basement membrane component in human and rat liver, accumulates in
      cirrhosis and hepatocellular carcinoma.
AB  - Agrin is a multifunctional heparan sulfate proteoglycan originally discovered in
      the neuromuscular junctions and later observed in numerous other localizations.
      The presence of agrin in the liver, either healthy or diseased, has formerly not
      been reported. We detected agrin in minor amounts in the basement membranes of
      blood vessels and bile ducts in the healthy liver. The proliferation of bile
      ductules and the formation of new septal blood vessels in liver cirrhosis, as
      well as neoangiogenesis in the hepatocellular carcinoma (HCC) result in a
      dramatic increase in the quantity of agrin. Vascular and peribiliary basement
      membranes were strongly immunopositive for agrin in 29/29 human liver specimens
      with cirrhosis and HCC. However, sinusoidal walls of regenerative nodules in the
      cirrhotic liver consistently remained negative. Given the selectivity of agrin
      for tumor microvessels, agrin immunohistochemistry may prove helpful in
      recognizing malignant transformation in cirrhotic livers. Similar
      immunohistochemical observations were made on the liver of rats exposed to a
      combined cirrhosis/HCC induction treatment. In both human and rats, agrin
      probably originates from activated myofibroblasts, vascular smooth muscle cells
      and biliary epithelial cells. Increased agrin expression in human specimens, in
      the liver of 4/4 treated rats, as well as in isolated rat liver mesenchymal cells
      was verified by quantitative RT-PCR. Considering that agrin binds various growth
      factors, and it directly interacts with cell membrane receptors such as alphav
      integrins, we hypothesize a stimulatory role for agrin in neoangiogenic processes
      such as tumor vascularization, and a supportive role in bile ductule
      proliferation.

PMID- 16983330
TI  - Defective hepatic regeneration after partial hepatectomy in leptin-deficient mice
      is not rescued by exogenous leptin.
AB  - Liver regeneration after partial hepatectomy (PH) is impaired in leptin-deficient
      ob/ob mice. Here, we tested whether exogenous leptin and/or correction of the
      obese phenotype (by food restriction or long-term leptin administration) would
      rescue hepatocyte proliferation and whether the hepatic progenitor cell
      compartment was activated in leptin-deficient ob/ob livers after PH. Because of
      the high mortality following 70% PH to ob/ob mice, we performed a less extensive
      (55%) resection. Compared to lean mice, liver regeneration after 55% PH was
      deeply impaired and delayed in ob/ob mice. Administration of exogenous leptin to
      ob/ob mice at doses that restored circulating leptin levels during the surgery
      and postsurgery period or for 3 weeks prior to the surgical procedure did not
      rescue defective liver regeneration. Moreover, correction of obesity, metabolic
      syndrome and hepatic steatosis by prolonged administration of leptin or food
      restriction (with or without leptin replacement at the time of PH) did not
      improve liver regeneration in ob/ob mice. The hepatic progenitor cell compartment
      was increased in ob/ob mice. However, after PH, the number of progenitor cells
      decreased and signs of proliferation were absent from this cell compartment. In
      this study, we have conclusively shown that neither leptin replacement nor
      amelioration of the metabolic syndrome, obese phenotype and hepatic steatosis,
      with or without restitution of normal circulating levels of leptin, was able to
      restore replicative competence to ob/ob livers after PH. Thus, leptin does not
      directly signal to liver cells to promote hepatocyte proliferation, and the obese
      phenotype is not solely responsible for impaired regeneration.

PMID- 16983331
TI  - Nonredundant roles of TIRAP and MyD88 in airway response to endotoxin,
      independent of TRIF, IL-1 and IL-18 pathways.
AB  - Inhaled endotoxins induce an acute inflammatory response in the airways mediated
      through Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88
      (MyD88). However, the relative roles of the TLR4 adaptor proteins TIRAP and TRIF
      and of the MyD88-dependent IL-1 and IL-18 receptor pathways in this response are
      unclear. Here, we demonstrate that endotoxin-induced acute bronchoconstriction,
      vascular damage resulting in protein leak, Th1 cytokine and chemokine secretion
      and neutrophil recruitment in the airways are abrogated in mice deficient for
      either TIRAP or MyD88, but not in TRIF deficient mice. The contribution of other
      TLR-independent, MyD88-dependent signaling pathways was investigated in IL-1R1,
      IL-18R and caspase-1 (ICE)-deficient mice, which displayed normal airway
      responses to endotoxin. In conclusion, the TLR4-mediated, bronchoconstriction and
      acute inflammatory lung pathology to inhaled endotoxin critically depend on the
      expression of both adaptor proteins, TIRAP and MyD88, suggesting cooperative
      roles, while TRIF, IL-1R1, IL-18R signaling pathways are dispensable.

PMID- 16983332
TI  - Expression of p53 and p53/47 are controlled by alternative mechanisms of
      messenger RNA translation initiation.
AB  - P53 controls the growth and survival of cells by acting in response to a
      multitude of cellular stresses. It is, however, not yet fully understood how
      different p53 activation pathways result in either cell cycle arrest or
      apoptosis. We and others have described an N-terminally truncated p53 protein
      (p53/47) originating from a second translation initiation site in the p53
      messenger RNA (mRNA), which can interact with p53 and impose altered stability
      and transactivation properties to p53 complexes. Here we show that cap-dependent
      and cap-independent mechanisms of initiation govern the translation of the p53
      mRNA. Changes in synthesis of full-length p53 or p53/47 are regulated through
      distinct cell stress-induced pathways acting through separate regions of the p53
      mRNA. We also show that some cytotoxic drugs require the presence of full-length
      p53 to induce apoptosis, whereas for others p53/47 is sufficient. This indicates
      that by harbouring alternative translation initiation sites, the p53 mRNA gives
      rise to different levels of the p53 isoforms which help to orchestrate the cell
      biological outcome of p53 activation in response to different types of cell
      stress. This sheds new light into the way p53 can integrate and differentiate a
      large multiplicity of changes in the cellular environment.

PMID- 16983333
TI  - Nitric oxide-mediated inhibition of androgen receptor activity: possible
      implications for prostate cancer progression.
AB  - Chronic inflammation increases the risk of cancer and many cancers, including
      prostate cancer, arise at sites of chronic inflammation. Inducible nitric oxide
      synthase (iNOS) is an enzyme dominantly expressed during inflammatory reactions.
      Although synthesis of high amounts of nitric oxide (NO) by iNOS has been
      demonstrated in pathophysiological processes, such as acute or chronic
      inflammation, autoimmune diseases or tumorigenesis, the role of iNOS activity in
      most of these diseases is poorly understood. Analysing prostate cancer biopsies
      by immunohistochemistry we found iNOS protein expression in tumor cells strongly
      paralleled by nitrotyrosine suggesting that iNOS is fully active. In vitro, NO
      inhibits androgen receptor-dependent promoter activity and prostate specific
      antigen production as well as DNA-binding activity of the androgen receptor (AR)
      in a concentration-dependent manner. Inhibition of the activity of androgen
      receptor-dependent reporter constructs is neither owing to diminished AR protein
      levels nor owing to an inhibition of its nuclear import. In addition, NO inhibits
      the proliferation of androgen receptor-positive prostate cancer cells
      significantly more efficiently than proliferation of androgen receptor-negative
      prostate cancer cells. In summary, our findings suggest that intratumoral iNOS
      activity favors development of prostate cancer cells that are able to proliferate
      androgen receptor-independently, thereby promoting prostate tumor progression.

PMID- 16983334
TI  - Cyclooxygenase inhibitors modulate the p53/HDM2 pathway and enhance chemotherapy
      induced apoptosis in neuroblastoma.
AB  - Cyclooxygenase-2 (COX-2) is upregulated in many tumors including neuroblastoma,
      and its overexpression has been implicated in resistance to p53-dependent
      apoptosis. Although p53 is rarely mutated in neuroblastoma, the p53 protein is
      rendered inactive via several mechanisms including sequestration in the
      cytoplasm. Here, we show that COX inhibitors inhibit the growth of neuroblastoma
      and when combined with low doses of chemotherapy, exert synergistic effects on
      neuroblastoma cells. Following COX inhibitor treatment, HDM2, which targets p53
      for ubiquitin-mediated degradation, is downregulated, resulting in an attenuation
      of p53 ubiquitination and an increase in p53 half-life. The level of HDM2
      phosphorylation at ser166, which influences both HDM2 and p53 subcellular
      distribution, is markedly diminished in response to COX inhibitors and is
      associated with increased p53 nuclear localization. Combining COX inhibitors with
      low-dose chemotherapy potentiates apoptosis and p53 stability, nuclear
      localization, and activity. p53 knockdown by siRNA resulted in the rescue of COX
      inhibitor-treated cells, indicating that COX inhibitor-induced apoptosis is, at
      least in part, p53-dependent. Taken together, these results provide the first
      evidence that COX inhibitors enhance chemosensitivity in neuroblastoma via
      downregulating HDM2 and augmenting p53 stability and nuclear accumulation.

PMID- 16983335
TI  - Distinct promoters mediate constitutive and inducible Bcl-XL expression in
      malignant lymphocytes.
AB  - Bcl-X(L) is a Bcl-2-related survival protein that is essential for normal
      development. Bcl-X(L) expression is rapidly induced by a wide range of survival
      signals and many cancer cells constitutively express high levels. The Bcl-X gene
      has a complex organization with multiple promoters giving rise to RNAs with
      alternate 5' non-coding exons. Here we have investigated the mechanisms that
      control basal and induced expression of Bcl-X(L) in B-lymphoma cells. Antisense
      experiments demonstrated that Bcl-X(L) was essential for survival of Akata6 B
      lymphoma cells. The levels of RNAs containing the IB Bcl-X non-coding exon,
      derived from the distal 1B promoter, correlated with basal expression of Bcl-X(L)
      in primary malignant B cells and this promoter was highly active in B-cell lines.
      The activity of this promoter was largely dependent on a single Ets binding site
      and Ets family proteins were bound at this promoter in intact cells. CD40 ligand
      (CD40L)-induced cell survival was associated with increased Bcl-X(L) expression
      and accumulation of exon IA-containing RNAs, derived from the proximal 1A
      promoter. Nuclear factor-kappaB (NF-kappaB) inhibition prevented induction of Bcl
      X(L) protein and exon IA-containing RNAs by CD40L. Therefore, the distal Bcl-X 1B
      promoter plays a critical role in driving constitutive expression-mediated via
      Ets family proteins in malignant B cells, whereas NF-kappaB plays a central role
      in the induction of Bcl-X(L) in response to CD40 signalling via the proximal 1A
      promoter.

PMID- 16983336
TI  - Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth
      involves suppression of angiogenesis.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional
      protein that induces apoptosis utilizing both insulin-like growth factor receptor
      (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP
      3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in
      severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections
      reduced tumor size and increased apoptosis and also led to a reduction in the
      number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular
      endothelial growth factor- and IGF-stimulated human umbilical vein endothelial
      cells vascular network formation in a matrigel assay. This action is primarily
      IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog
      Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug
      assay and chick allantoic membrane assays to show that IGFBP-3 has potent
      antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF
      binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and
      the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that
      the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together,
      these studies provide the first evidence that IGFBP-3 has direct, IGF-independent
      inhibitory effects on angiogenesis providing an additional mechanism by which it
      exerts its tumor suppressive effects and further supporting its development for
      clinical use in the therapy of patients with prostate cancer.

PMID- 16983337
TI  - MUC1 is a novel regulator of ErbB1 receptor trafficking.
AB  - ErbB receptors are key regulators of cell survival and growth in normal and
      transformed tissues. The oncogenic glycoprotein MUC1 is a binding partner and
      substrate for erbB1 and MUC1 expression can potentiate erbB-dependent signal
      transduction. After receptor activation, erbB1 is typically downregulated via an
      endocytic pathway that results in receptor degradation or recycling. We report
      here that MUC1 expression inhibits the degradation of ligand-activated erbB1.
      Through the use of both RNAi-mediated knock down and overexpression constructs of
      MUC1, we show that MUC1 expression inhibits erbB1 degradation after ligand
      treatment in breast epithelial cells. This MUC1-mediated protection against erbB1
      degradation can increase total cellular pools of erbB1 over time. Biotinylation
      of surface proteins demonstrates that cell-surface associated erbB1 receptor is
      protected by MUC1 against ligand-induced degradation, although this is
      accompanied by an increase in erbB1 internalization. The MUC1-mediated protection
      against degradation occurs with a decrease in EGF-stimulated ubiquitination of
      erbB1, and an increase in erbB1 recycling. These data indicate that MUC1
      expression is a potent regulator of erbB1 receptor stability upon activation and
      may promote transformation through the inhibition of erbB1 degradation.

PMID- 16983338
TI  - Apoptosis induced by proteasome inhibition in cancer cells: predominant role of
      the p53/PUMA pathway.
AB  - The proteasome has emerged as a novel target for antineoplastic treatment of
      hematological malignancies and solid tumors, including those of the central
      nervous system. To identify cell death pathways activated in response to
      inhibition of the proteasome system in cancer cells, we treated human SH-SY5Y
      neuroblastoma cells with the selective proteasome inhibitor (PI) epoxomicin
      (Epoxo). Prolonged exposure to Epoxo was associated with increased levels of poly
      ubiquitinylated proteins and p53, release of cytochrome c from the mitochondria,
      and activation of caspases. Analysis of global gene expression using high-density
      oligonucleotide microarrays revealed that Epoxo triggered transcriptional
      activation of the two Bcl-2-homology domain-3-only (BH3-only) genes p53
      upregulated modulator of apoptosis (PUMA) and Bim. Subsequent studies in PUMA-
      and Bim-deficient cells indicated that Epoxo-induced caspase activation and
      apoptosis was predominantly PUMA-dependent. Further characterization of the
      transcriptional response to Epoxo in HCT116 human colon cancer cells demonstrated
      that PUMA induction was p53-dependent; with deficiency in either p53 or PUMA
      significantly protected HCT116 cells against Epoxo-induced apoptosis. Our data
      suggest that p53 activation and the transcriptional induction of its target gene
      PUMA play an important role in the sensitivity of cancer cells to apoptosis
      induced by proteasome inhibition, and imply that antineoplastic therapies with
      PIs might be especially useful in cancers with functional p53.

PMID- 16983339
TI  - Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis.
AB  - D-type cyclins are components of the cell-cycle engine that link cell signaling
      pathways and passage throughout G1 phase. We previously described the effects of
      overexpression cyclin D1, D2 or D3 in mouse epidermis and tumor development. We
      now asked whether cyclin D2 and/or cyclin D3 play a relevant role in ras
      dependent tumorigenesis. Here, we described the effect of cyclin D3 and cyclin D2
      overexpression in mouse skin tumor development. Notably, overexpression of cyclin
      D3 results in reduced tumor development and malignant progression to squamous
      cell carcinomas (SCC). Biochemical analysis of keratinocytes shows that
      overexpression of cyclin D3 results in strong reduction of cyclin D2 and its
      associated kinase activity. Furthermore, we found that reinstatement of cyclin D2
      level in the cyclin D3/cyclin D2 bigenic mice results in a complete reversion of
      the inhibitory action of cyclin D3. Supporting these results, ablation of cyclin
      D2 results in reduced tumorigenesis and malignant progression. On the other hand,
      overexpression of cyclin D2 results in an increased number of papillomas and
      malignant progression. We conclude that cyclin D3 and cyclin D2 play opposite
      roles in mouse skin tumor development and that the suppressive activity of cyclin
      D3 is associated with cyclin D2 downregulation.

PMID- 16983340
TI  - Sustained leukaemic phenotype after inactivation of BCR-ABLp190 in mice.
AB  - Pharmacological inactivation of cancer genes or products is being used as a
      strategy for therapy in oncology. To investigate the potential role of BCR
      ABLp190 cessation in leukaemia development, we generated mice carrying a
      tetracycline-repressible BCR-ABLp190 transgene. These mice were morphologically
      normal at birth, and developed leukaemias. Disease was characterized by the
      presence of B-cell blasts co-expressing myeloid markers, reminiscent of the human
      counterpart. BCR-ABLp190 activation can initiate leukaemia in both young and
      adult mice. Transitory expression of BCR-ABLp190 is enough to develop leukaemia.
      Suppression of the BCR-ABLp190 transgene in leukaemic CombitTA-p190 mice did not
      rescue the malignant phenotype, indicating that BCR-ABLp190 is not required to
      maintain the disease in mice. Similar results were obtained by inactivation of
      BCR-ABLp190 with STI571 (Gleevec; Novartis, East Hanover, NJ, USA) in leukaemic
      CombitTA-p190 mice. However, gradual suppression of BCR-ABLp190 in leukaemic
      CombitTA-p190 mice identified a minimum level of BCR-ABLp190 expression necessary
      to revert the specific block in B-cell differentiation in the leukaemic cells.
      Overall, the findings indicate that BCR-ABLp190 appears to cause epigenetic
      and/or genetic changes in tumour-maintaining cells that render them insensitive
      to BCR-ABLp190 inactivation.

PMID- 16983341
TI  - Matriptase inhibition by hepatocyte growth factor activator inhibitor-1 is
      essential for placental development.
AB  - Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a Kunitz-type
      transmembrane serine protease inhibitor that forms inhibitor complexes with
      several trypsin-like serine proteases and is required for mouse placental
      development and embryo survival. Here we show that the essential function of HAI
      1 in placentation and all other embryonic processes is to restrict the activity
      of the type II transmembrane serine protease, matriptase. Enzymatic gene trapping
      of matriptase combined with HAI-1 immunohistochemistry revealed that matriptase
      is co-expressed with HAI-1 in both extraembryonic and embryonic tissues. As early
      as embryonic day 8.5, matriptase and HAI-1 were expressed in a population of
      chorionic trophoblasts. Ablation of HAI-1 disrupted the epithelial integrity of
      this cell population, causing disorganized laminin deposition and altered
      expression of E-cadherin and beta-catenin. This led to a complete loss of
      undifferentiated chorionic trophoblasts after embryonic day 9.5 and prevented the
      formation of the placental labyrinth. Genetic ablation of matriptase activity in
      HAI-1-deficient embryos, however, restored the integrity of chorionic
      trophoblasts and enabled placental labyrinth formation and development to term.
      Furthermore, matriptase/HAI-1 double-deficient mice were phenotypically
      indistinguishable from matriptase single-deficient littermates.

PMID- 16983342
TI  - Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem
      cell regulator C/EBPalpha by inhibiting its ubiquitination.
AB  - Functional inactivation of transcription factors in hematopoietic stem cell
      development is involved in the pathogenesis of acute myeloid leukemia (AML). Stem
      cell regulator C/enhancer binding protein (EBP)alpha is among such transcription
      factors known to be inactive in AML. This is either due to mutations or
      inhibition by protein-protein interactions. Here, we applied a mass spectrometry
      based proteomic approach to systematically identify putative co-activator
      proteins interacting with the DNA-binding domain (DBD) of C/EBP transcription
      factors. In our proteomic screen, we identified c-Jun N-terminal kinase (JNK) 1
      among others such as PAK6, MADP-1, calmodulin-like skin proteins and ZNF45 as
      proteins interacting with DBD of C/EBPs from nuclear extract of myelomonocytic
      U937 cells. We show that kinase JNK1 physically interacts with DBD of C/EBPalpha
      in vitro and in vivo. Furthermore, we show that active JNK1 inhibits
      ubiquitination of C/EBPalpha possibly by phosphorylating in its DBD.
      Consequently, JNK1 prolongs C/EBPalpha protein half-life leading to its enhanced
      transactivation and DNA-binding capacity. In certain AML patients, however, the
      JNK1 mRNA expression and its kinase activity is decreased which suggests a
      possible reason for C/EBPalpha inactivation in AML. Thus, we report the first
      proteomic screen of C/EBP-interacting proteins, which identifies JNK1 as positive
      regulator of C/EBPalpha.

PMID- 16983343
TI  - Sperm-associated antigen 1 is expressed early in pancreatic tumorigenesis and
      promotes motility of cancer cells.
AB  - Sperm-associated antigen 1 (SPAG1) was recently identified in a rare form of
      infertility where anti-SPAG1 antibodies derived from the serum of an infertile
      woman were reported to cause sperm agglutination. Except for its expression and
      potential role in spermatogenesis, the function of SPAG1 is completely unknown.
      The unexpected finding of high levels of SPAG1 expression in pancreatic
      adenocarcinoma compared to normal pancreatic tissue in our previous cDNA array
      experiments prompted us to look in more detail at the expression and role of this
      gene in a panel of normal and malignant human tissues as well as in a larger
      series of pancreatic cancer specimens. We have generated an SPAG1-specific
      monoclonal antibody and showed high levels of SPAG1 protein in testis and in a
      large proportion of pancreatic ductal adenocarcinomas (PDAC). In the latter,
      SPAG1 expression was predominantly cytoplasmic and confined to malignant cells.
      Furthermore, the extent and intensity of SPAG1 expression was shown to be
      associated with stage and tumour nodal status, while analysis of precursor
      lesions, pancreatic intraepithelial neoplasias (PanINs), demonstrated its
      increased immunoreactivity with increasing PanIN grade, suggesting that SPAG1 is
      a novel marker of PDAC progression. Immunocytochemical analysis demonstrated
      colocalization of SPAG1 with microtubules, and their association was confirmed by
      co-immunoprecipitation; subsequent motility assays further substantiated a
      potential role of SPAG1 in cancer cell motility. Combined with the finding of its
      early expression in PDAC development, our data suggest that SPAG1 could
      contribute to the early spread and poor prognosis of pancreatic adenocarcinoma.

PMID- 16983344
TI  - Viral oncoproteins target the DNA methyltransferases.
AB  - Small DNA tumour viruses have evolved a number of mechanisms to drive nondividing
      cells into S phase. Virally encoded oncoproteins such as adenovirus E1A and human
      papillomavirus (HPV) E7 can bind an array of cellular proteins to override
      proliferation arrest. The DNA methyltransferase Dnmt1 is the major mammalian
      enzyme responsible for maintaining CpG methylation patterns in the cell following
      replication. One of the hallmarks of tumour cells is disrupted DNA methylation
      patterns, highlighting the importance of the proper regulation of DNA
      methyltransferases in normal cell proliferation. Here, we show that adenovirus 5
      E1A and HPV-16 E7 associate in vitro and in vivo with the DNA methyltransferase
      Dnmt1. Consistent with this interaction, we find that E1A and E7 can purify DNA
      methyltransferase activity from nuclear extracts. These associations are direct
      and mediated by the extreme N-terminus of E1A and the CR3 zinc-finger domain of
      E7. Furthermore, we find that a point mutant at leucine 20 of E1A, a residue
      known to be critical for its transformation functions, is unable to bind Dnmt1
      and DNA methyltransferase activity. Finally, both E1A and E7 can stimulate the
      methyltransferase activity of Dnmt1 in vitro. Our results provide the first
      indication that viral oncoproteins bind and regulate Dnmt1 enzymatic activity.
      These observations open up the possibility that this association may be used to
      control cellular proliferation pathways and suggest a new mechanism by which
      small DNA tumour viruses can steer cells through the cell cycle.

PMID- 16983345
TI  - Transcription linked to recombination: a gene-internal promoter coincides with
      the recombination hot spot II of the human MLL gene.
AB  - The MLL gene is frequently involved in chromosomal translocations associated with
      high-risk acute leukaemia. Infant and therapy-related acute leukaemia patients
      display chromosomal breakpoints preferentially clustered in the telomeric portion
      of the MLL breakpoint cluster region (SCII). Here, we demonstrate that SCII
      colocalizes with a gene-internal promoter element in the mouse and human MLL
      gene, respectively. The mRNA generated encodes an N-terminally truncated version
      of MLL that still exhibits many functional regions, including the C-terminal SET
      domain. Etoposide-induced DNA double-strand breaks colocalize with the binding
      site of RNA polymerase II and the transcription initiation region, but not with a
      nearby Topo II consensus sequence. Thus, the observed genomic instability of the
      human MLL gene is presumably linked to transcriptional processes. The
      consequences of this novel finding for the creation of chromosomal
      translocations, the biology of the MLL protein and for MLL-mediated acute
      leukaemia are discussed.

PMID- 16983346
TI  - HIV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous
      recombination.
AB  - An ATM-dependent cellular signal, a DNA-damage response, has been shown to be
      involved during infection of human immunodeficiency virus type-1 (HIV-1), and a
      high incidence of malignant tumor development has been observed in HIV-1-positive
      patients. Vpr, an accessory gene product of HIV-1, delays the progression of the
      cell cycle at the G2/M phase, and ATR-Chk1-Wee-1, another DNA-damage signal, is a
      proposed cellular pathway responsible for the Vpr-induced cell cycle arrest. In
      this study, we present evidence that Vpr also activates ATM, and induces
      expression of gamma-H2AX and phosphorylation of Chk2. Strikingly, Vpr was found
      to stimulate the focus formation of Rad51 and BRCA1, which are involved in repair
      of DNA double-strand breaks (DSBs) by homologous recombination (HR), and
      biochemical analysis revealed that Vpr dissociates the interaction of p53 and
      Rad51 in the chromatin fraction, as observed under irradiation-induced DSBs. Vpr
      was consistently found to increase the rate of HR in the locus of I-SceI, a rare
      cutting-enzyme site that had been introduced into the genome. An increase of the
      HR rate enhanced by Vpr was attenuated by an ATM inhibitor, KU55933, suggesting
      that Vpr-induced DSBs activate ATM-dependent cellular signal that enhances the
      intracellular recombination potential. In context with a recent report that
      KU55933 attenuated the integration of HIV-1 into host genomes, we discuss the
      possible role of Vpr-induced DSBs in viral integration and also in HIV-1
      associated malignancy.

PMID- 16983347
TI  - Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death:
      Relationship to Bcl-2 family and caspase activation.
AB  - In order to define genetic determinants of primary and metastatic melanoma cell
      susceptibility to tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary
      T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1
      and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2%
      of which displayed differential expression in G1 and T1 cells. Cell
      susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene
      expression signatures in this model. Some of the differentially expressed genes
      were identified as involved in ATP-binding and signaling pathways, based on
      previously published data. Further analysis provided evidences that c-kit was
      overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor,
      imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL
      resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and
      TRAIL-mediated apoptosis in melanoma cells. We investigated the possible
      involvement of several molecules, including c-ABL, platelet-derived growth factor
      receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like
      inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1),
      proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib
      did not modulate the expression or activation of its own targets, such as c-ABL,
      PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2
      associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1
      cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells
      previously treated with imatinib. More notably, we found that the resistance to
      TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the
      DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L)
      knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the
      expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a
      crucial role in determining TRAIL resistance in metastatic melanoma cells. Our
      results also show that imatinib enhances TRAIL-induced cell death independently
      of BH3-interacting domain death agonist translocation, in a process involving the
      Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and
      caspase activation. Our data indicate that imatinib sensitizes T1 cells by
      directly downregulating c-FLIP(L), with the use of an alternative pathway for
      antitumor activity, because PDGFRalpha is not activated in T1 cells and these
      cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and
      mitochondria also play a key role in the imatinib-mediated sensitization of
      melanoma cells to the proapoptotic action of TRAIL.

PMID- 16983372
TI  - Modern computational approaches for analysing molecular genetic variation data.
AB  - An explosive growth is occurring in the quantity, quality and complexity of
      molecular variation data that are being collected. Historically, such data have
      been analysed by using model-based methods. Models are useful for sharpening
      intuition, for explanation and for prediction: they add to our understanding of
      how the data were formed, and they can provide quantitative answers to questions
      of interest. We outline some of these model-based approaches, including the
      coalescent, and discuss the applicability of the computational methods that are
      necessary given the highly complex nature of current and future data sets.

PMID- 16983373
TI  - Genetic relatedness analysis: modern data and new challenges.
AB  - Individuals who belong to the same family or the same population are related
      because of their shared ancestry. Population and quantitative genetics theory is
      built with parameters that describe relatedness, and the estimation of these
      parameters from genetic markers enables progress in fields as disparate as plant
      breeding, human disease gene mapping and forensic science. The large number of
      multiallelic microsatellite loci and biallelic SNPs that are now available have
      markedly increased the precision with which relationships can be estimated,
      although they have also revealed unexpected levels of genomic heterogeneity of
      relationship measures.

PMID- 16983374
TI  - A tutorial on statistical methods for population association studies.
AB  - Although genetic association studies have been with us for many years, even for
      the simplest analyses there is little consensus on the most appropriate
      statistical procedures. Here I give an overview of statistical approaches to
      population association studies, including preliminary analyses (Hardy-Weinberg
      equilibrium testing, inference of phase and missing data, and SNP tagging), and
      single-SNP and multipoint tests for association. My goal is to outline the key
      methods with a brief discussion of problems (population structure and multiple
      testing), avenues for solutions and some ongoing developments.

PMID- 16983375
TI  - Spreading of silent chromatin: inaction at a distance.
AB  - One of the oldest unsolved problems in genetics is the observation that gene
      silencing can 'spread' along a chromosome. Although spreading has been widely
      perceived as a process of long-range assembly of heterochromatin proteins, such
      'oozing' might not apply in most cases. Rather, long-range silencing seems to be
      a dynamic process, involving local diffusion of histone-modifying enzymes from
      source binding sites to low-affinity sites nearby. Discontinuous silencing might
      reflect looping interactions, whereas the spreading of continuous silencing might
      be driven by the processive movement of RNA or DNA polymerases. We review the
      evidence for the spreading of silencing in many contexts and organisms and
      conclude that multiple mechanisms have evolved that silence genes at a distance.

PMID- 16983376
TI  - TAR cloning: insights into gene function, long-range haplotypes and genome
      structure and evolution.
AB  - The structural and functional analysis of mammalian genomes would benefit from
      the ability to isolate from multiple DNA samples any targeted chromosomal segment
      that is the size of an average human gene. A cloning technique that is based on
      transformation-associated recombination (TAR) in the yeast Saccharomyces
      cerevisiae satisfies this need. It is a unique tool to selectively recover
      chromosome segments that are up to 250 kb in length from complex genomes. In
      addition, TAR cloning can be used to characterize gene function and genome
      variation, including polymorphic structural rearrangements, mutations and the
      evolution of gene families, and for long-range haplotyping.

PMID- 16983377
TI  - Genes, environment and the value of prospective cohort studies.
AB  - Case-control studies have many advantages for identifying disease-related genes,
      but are limited in their ability to detect gene-environment interactions. The
      prospective cohort design provides a valuable complement to case-control studies.
      Although it has disadvantages in duration and cost, it has important strengths in
      characterizing exposures and risk factors before disease onset, which reduces
      important biases that are common in case-control studies. This and other
      strengths of prospective cohort studies make them invaluable for understanding
      gene-environment interactions in complex human disease.

PMID- 16983379
TI  - Learning science like a scientist.

PMID- 16983380
TI  - The inorganic side of chemical biology.
AB  - Bioinorganic chemistry remains a vibrant discipline at the interface of chemistry
      and the biological sciences. Metal ions function in numerous metalloenzymes, are
      incorporated into pharmaceuticals and imaging agents, and inspire the synthesis
      of catalysts used to achieve many chemical transformations.

PMID- 16983381
TI  - Flipping the safety catch of procaspase-3.

PMID- 16983382
TI  - Cyclization of natural products.

PMID- 16983383
TI  - Breaking the silence in Friedreich's ataxia.

PMID- 16983384
TI  - Engineering a multipurpose catalyst.

PMID- 16983385
TI  - How complex is a complex?

PMID- 16983387
TI  - Therapeutic intervention based on protein prenylation and associated
      modifications.
AB  - In eukaryotic cells, a specific set of proteins are modified by C-terminal
      attachment of 15-carbon farnesyl groups or 20-carbon geranylgeranyl groups that
      function both as anchors for fixing proteins to membranes and as molecular
      handles for facilitating binding of these lipidated proteins to other proteins.
      Additional modification of these prenylated proteins includes C-terminal
      proteolysis and methylation, and attachment of a 16-carbon palmitoyl group; these
      modifications augment membrane anchoring and alter the dynamics of movement of
      proteins between different cellular membrane compartments. The enzymes in the
      protein prenylation pathway have been isolated and characterized. Blocking
      protein prenylation is proving to be therapeutically useful for the treatment of
      certain cancers, infection by protozoan parasites and the rare genetic disease
      Hutchinson-Gilford progeria syndrome.

PMID- 16983389
TI  - Two isoforms of GABA(A) receptor beta2 subunit with different
      electrophysiological properties: Differential expression and genotypical
      correlations in schizophrenia.
AB  - Single nucleotide polymorphisms in type A gamma-aminobutyric acid (GABA(A))
      receptor beta2 subunit gene (GABRB2) were found to be associated with
      schizophrenia in Chinese, German, Japanese and Portuguese. To explore potential
      functional consequences of these DNA sequence polymorphisms, this study examined
      the expression and electrophysiological properties of two alternatively spliced
      products of GABRB2 along with genotypical disease association analysis. Real-time
      quantitative polymerase chain reaction, performed with a cohort of 31
      schizophrenics and 31 controls of US population, showed 21.7% reduction in the
      expression of the long isoform beta(2L), 13.4% in the short isoform beta(2S) and
      15.8% in the sum of the two isoforms beta(2T) in postmortem schizophrenic brain.
      Furthermore, two independent mRNA quantitation methods showed that the relative
      expression of the long over the short isoforms was significantly decreased,
      suggesting the occurrence of altered splicing, in schizophrenia. In male
      schizophrenics, the heterozygous genotypes of rs1876071 (T/C) and rs1876072 (A/G)
      were correlated with reduced expression of beta(2L), beta(2S) and beta(2T), and
      the heterozygous of rs2546620 (A/G) and homozygous-minor of rs1876071 (C/C) and
      rs1876072 (G/G) were correlated with reduced expression of beta(2T). Significant
      correlations of expression levels with different alleles and haplotypes were also
      indicated by quantitative trait analysis. Recombinant GABA(A) receptors expressed
      in HEK293 human cells containing beta(2L) underwent a steeper current rundown
      upon repetitive GABA activation than receptors containing beta(2S). The results
      thus revealed genotype-dependent expression of the alternatively spliced isoforms
      of GABA(A) receptor beta2 subunit, giving rise to electrophysiological
      consequences that could play an important role in the pathogenesis mechanism of
      schizophrenia.

PMID- 16983390
TI  - Prefrontal hyperactivation during working memory task in untreated individuals
      with major depressive disorder.
AB  - The prefrontal cortex, a part of the limbic-thalamic-cortical network,
      participates in regulation of mood, cognition and behavior and has been
      implicated in the pathophysiology of major depressive disorder (MDD). Many
      neuropsychological studies demonstrate impairment of working memory in patients
      with MDD. However, there are few functional neuroimaging studies of MDD patients
      during working memory processing, and most of the available ones included
      medicated patients or patients with both MDD and bipolar disorder. We used
      functional magnetic resonance imaging (fMRI) to measure prefrontal cortex
      function during working memory processing in untreated depressed patients with
      MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of
      Mental Disorders-Fourth Edition recurrent MDD (mean age+/-s.d.=34.3+/-11.5 years)
      and 15 healthy comparison subjects (37.7+/-12.1 years) matched for age, sex and
      race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence
      was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back)
      was used to elicit frontal cortex activation. Data were analyzed with a multiple
      regression analysis using the FSL-FEAT software. MDD patients showed
      significantly greater left dorsolateral cortex activation during the n-back task
      compared to the healthy controls (P<0.01), although task performance was similar
      in the two groups. Furthermore, the patients showed significant anterior
      cingulate cortex activation during the task, but the comparison subjects did not
      (P<0.01). This study provides in vivo imaging evidence of abnormal frontolimbic
      circuit function during working memory processing in individuals with MDD.

PMID- 16983392
TI  - Dietary n-3 PUFA deprivation alters expression of enzymes of the arachidonic and
      docosahexaenoic acid cascades in rat frontal cortex.
AB  - The enzymes that regulate the brain arachidonic acid (AA) cascade have been
      implicated in bipolar disorder and neuroinflammation. Fifteen weeks of dietary n
      3 polyunsaturated fatty acid (PUFA) deprivation in rats decreases the
      concentration of docosahexaenoic acid (DHA) and increases its half-life within
      the brain. Based on this, we hypothesized that such dietary deprivation would
      decrease expression of enzymes responsible for the metabolic loss of DHA while
      increasing expression of those responsible for the metabolism of AA. Fifteen
      weeks of n-3 PUFA deprivation significantly decreased the activity, protein and
      mRNA expression of the DHA regulatory phospholipase A2 (PLA2), calcium
      independent iPLA2, in rat frontal cortex. In contrast the activities, protein and
      mRNA levels of the AA selective calcium-dependent cytosolic phospholipase (cPLA2)
      and secretory sPLA2 were increased. Cyclooxygenase (COX)-1 protein but not mRNA
      was decreased in the n-3 PUFA-deprived rats whereas COX-2 protein and mRNA were
      increased. This study suggests that n-3 PUFA deprivation increases the half-live
      of brain DHA by downregulating iPLA2. The finding that n-3 PUFA deprivation
      increases cPLA2, sPLA2 and COX-2 is opposite to what has been reported after
      chronic administration of anti-manic agents to rats and suggests that n-3 PUFA
      deprivation may increase susceptibility to bipolar disorder.

PMID- 16983391
TI  - n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF
      via a p38 MAPK-dependent mechanism.
AB  - Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF)
      have been implicated in bipolar disorder. It also has been reported that dietary
      deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats,
      increased their depression and aggression scores. Here, we show that n-3 PUFA
      deprivation for 15 weeks decreased the frontal cortex DHA level and reduced
      frontal cortex BDNF expression, cAMP response element binding protein (CREB)
      transcription factor activity and p38 mitogen-activated protein kinase (MAPK)
      activity. Activities of other CREB activating protein kinases were not
      significantly changed. The addition of DHA to rat primary cortical astrocytes in
      vitro, induced BDNF protein expression and this was blocked by a p38 MAPK
      inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may
      contribute to its therapeutic efficacy in brain diseases having disordered cell
      survival and neuroplasticity.

PMID- 16983393
TI  - Efficacy and tolerability of the dual 5alpha-reductase inhibitor, dutasteride, in
      the treatment of benign prostatic hyperplasia in African-American men.
AB  - The efficacy and tolerability of dutasteride (0.5 mg daily for 2 years) in
      African-Americans (n=161), compared with Caucasians (n=3961), was assessed in a
      post hoc analysis of data from three Phase III clinical trials. Dutasteride
      significantly reduced serum dihydrotestosterone levels by >90% and significantly
      improved subjective (symptom score) and objective (prostate volume, peak urinary
      flow rate, risk of benign prostatic hyperplasia-related surgery and acute urinary
      retention) outcomes in both African-Americans and Caucasians. For all efficacy
      measures, there was no statistically significant treatment-by-race interaction
      and dutasteride was well tolerated in both racial groups. Therefore, dutasteride
      demonstrated similar efficacy and safety profiles in African-Americans and
      Caucasians.

PMID- 16983394
TI  - Comparison of late gastrointestinal and genitourinary toxicity of prostate cancer
      patients undergoing intensity-modulated versus conventional radiotherapy using
      localized fields.
AB  - To compare late genitourinary (GU) and gastrointestinal (GI) toxicity of
      radiotherapy (RT) to localized fields for prostate cancer delivered using
      intensity-modulated RT (IMRT) versus conventional RT (ConvRT). The records of 461
      patients were reviewed; 355 patients received IMRT and 106 received ConvRT. Late
      GU and GI toxicity were compared. Late GU toxicity rates were not significantly
      different (P=0.166); however, late GI toxicity rates were lower with IMRT
      (P=0.001). Regression analyses demonstrated that only IMRT use (P=0.006)
      predicted reduction in late GI toxicity but no factors correlated with late GU
      toxicity. IMRT did not influence late GU toxicity but was associated with a
      reduction of late GI toxicity over ConvRT.

PMID- 16983395
TI  - Persistently high levels of immunosuppressive cytokines in patients after radical
      prostatectomy.
AB  - A significant proportion of men undergoing 'curative' radical prostatectomy (RP)
      for organ-confined prostate cancer relapse within 5 years. A number of adverse
      risk factors have been identified, but to date no adjuvant treatment as improved
      the outlook for these men. We proposed that these patients, despite small tumour
      burdens, may be immunosuppressed from their cancer, which may be amenable to
      immune modulation. We investigated their immune profile using sensitive
      functional cytokine assays, both pre- and post-surgery. In comparison with
      controls, RP patients expressed higher levels of both T helper type 1 (Th1)
      (interleukin (IL)-2 and tumour necrosis factor-alpha) and Th2 cytokines (IL-4, -5
      and -10) with little change after removal of tumour. Further analysis based on
      known poor-prognostic factors indicated a trend to expression of higher levels of
      Th2 cytokines IL-4 and IL-5 in worse prognosis patients rather than the mixed
      Th1/2 found across the whole cohort. Persistently high levels of both Th1 and Th2
      cytokines were detected in RP compared to control patients, despite the removal
      of relatively small tumour burdens. Cytokine expression studies may be useful as
      surrogate marker of potential disease progression, and could be used to identify
      patients who may benefit from immune modulation post-surgery.

PMID- 16983396
TI  - Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and
      its administration is associated with a reduced prostate-specific antigen
      velocity in a phase II clinical study.
AB  - Interest in lycopene has focused primarily on its use in the chemoprevention of
      prostate cancer (CaP); there are few clinical trials involving men with
      established disease. In addition, most data examining its mechanism of action
      have been obtained from experiments using immortal cell lines. We report the
      inhibitory effect(s) of lycopene in primary prostate epithelial cell (PEC)
      cultures, and the results of a pilot phase II clinical study investigating whole
      tomato lycopene supplementation on the behavior of established CaP, demonstrating
      a significant and maintained effect on prostate-specific antigen velocity over 1
      year. These data reinforce the justification for a large, randomized, placebo
      controlled study.

PMID- 16983398
TI  - A novel polymorphism in the 17beta-hydroxysteroid dehydrogenase type 5 (aldo-keto
      reductase 1C3) gene is associated with lower serum testosterone levels in
      caucasian men.
AB  - Genetic variation in the androgen metabolizing enzymes is important to identify
      and feature as they may influence the risk of prostate cancer and help clarify
      the etiology of the disease. Human 17beta-hydroxysteroid dehydrogenase type 5
      (AKR1C3) is highly expressed in the prostate gland and plays a major role in the
      formation and metabolism of androgens. We identified five novel polymorphisms in
      the AKR1C3 gene. One of those an A>G substitution in exon 2 that confers a
      Glu77Gly change occurred in 4.8% in Caucasians but was completely absent in
      Orientals. Interestingly, the testosterone level in serum was significantly lower
      in subjects with the Gly77 allele. A promoter A>G polymorphism was associated
      with significantly altered promoter activity in reporter constructs, but was not
      associated with any change in testosterone levels. In conclusion, the Glu77Gly
      polymorphism is associated with lower testosterone levels in serum.

PMID- 16983399
TI  - No evidence for binding of clozapine, olanzapine and/or haloperidol to selected
      receptors involved in body weight regulation.
AB  - The underlying mechanisms of antipsychotic (AP)-induced weight gain are unknown,
      but both central and peripheral AP target receptors could potentially be
      involved. This study used radioligand binding assays to compare the binding
      affinities of clozapine, olanzapine and haloperidol for candidate receptors
      potentially involved in AP-induced weight gain. Selected candidates derived from
      known pathways involved in body weight regulation included receptors classified
      as anorexigenic (bombesin receptor subtype 3, calcitonin gene-related peptide
      receptor, cholecystokinin receptor, melanocortin-4 receptor, neurotensin receptor
      1) or orexigenic (cannabinoid receptor 1, galanin 1 receptor, melanin
      concentrating hormone receptor (MCHR), neuropeptide Y1 receptor) as well as
      receptors involved in physiological actions related to digestion and fluid
      homeostasis (angiotensin II type 1 receptor, bradykinin B2 receptor, endothelin
      receptor, neurokinin 1 receptor, vasoactive intestinal polypeptide receptor 1).
      Clozapine, olanzapine and haloperidol exhibited negligible affinities to all of
      these receptors except for the MCHR (Ki=501 nM; haloperidol). With respect to
      other candidates from (neuro)transmitter systems already suggested to be involved
      in AP-induced weight gain, the binding profile of olanzapine resembled that of
      clozapine, with high affinity (Ki<10 nM) for serotonin (5-HT) 5-HT2A, 5-HT2C and
      5-HT6, muscarinic M1 and histamine H1 receptors. In contrast, the binding profile
      of haloperidol was substantially different (high affinity only for the dopamine
      D1 receptor). In conclusion, we have not identified a novel binding site of the
      two investigated atypical AP that could contribute to the induced weight gain.

PMID- 16983400
TI  - Pharmacogenetics of warfarin: current status and future challenges.
AB  - Warfarin is an anticoagulant that is difficult to use because of the wide
      variation in dose required to achieve a therapeutic effect, and the risk of
      serious bleeding. Warfarin acts by interfering with the recycling of vitamin K in
      the liver, which leads to reduced activation of several clotting factors. Thirty
      genes that may be involved in the biotransformation and mode of action of
      warfarin are discussed in this review. The most important genes affecting the
      pharmacokinetic and pharmacodynamic parameters of warfarin are CYP2C9 (cytochrome
      P(450) 2C9) and VKORC1 (vitamin K epoxide reductase complex subunit 1). These two
      genes, together with environmental factors, partly explain the interindividual
      variation in warfarin dose requirements. Large ongoing studies of genes involved
      in the actions of warfarin, together with prospective assessment of environmental
      factors, will undoubtedly increase the capacity to accurately predict warfarin
      dose. Implementation of pre-prescription genotyping and individualized warfarin
      therapy represents an opportunity to minimize the risk of haemorrhage without
      compromising effectiveness.

PMID- 16983401
TI  - Deficit of mitochondria-derived ATP during oxidative stress impairs mouse MII
      oocyte spindles.
AB  - Although the role of oxidative stress in maternal aging and infertility has been
      suggested, the underlying mechanisms are not fully understood. The present study
      is designed to determine the relationship between mitochondrial function and
      spindle stability in metaphase II (MII) oocytes under oxidative stress. MII mouse
      oocytes were treated with H2O2 in the presence or absence of permeability
      transition pores (PTPs) blockers cyclosporin A (CsA). In addition, antioxidant N
      acetylcysteine (NAC), F0/F1 synthase inhibitor oligomycin A, the mitochondria
      uncoupler carbonyl cyanide 4-trifluoro-methoxyphenylhydrazone (FCCP) or
      thapsigargin plus 2.5 mM Ca2+ (Th+2.5 mM Ca2+) were used in mechanistic studies.
      Morphologic analyses of oocyte spindles and chromosomes were performed and
      mitochondrial membrane potential (DeltaPsim), cytoplasmic free calcium
      concentration ([Ca2+]c) and cytoplasmic ATP content within oocytes were also
      assayed. In a time- and H2O2 dose-dependent manner, disruption of meiotic
      spindles was found after oocytes were treated with H2O2, which was prevented by
      pre-treatment with NAC. Administration of H2O2 led to a dissipation of DeltaPsim,
      an increase in [Ca2+]c and a decrease in cytoplasmic ATP levels. These
      detrimental responses of oocytes to H2O2 treatment could be blocked by pre
      incubation with CsA. Similar to H2O2, both oligomycin A and FCCP dissipated
      DeltaPsim, decreased cytoplasmic ATP contents and disassembled MII oocyte
      spindles, while high [Ca2+]c alone had no effects on spindle morphology. In
      conclusion, the decrease in mitochondria-derived ATP during oxidative stress may
      cause a disassembly of mouse MII oocyte spindles, presumably due to the opening
      of the mitochondrial PTPs.

PMID- 16983402
TI  - Identification of gene polymorphisms of human DNA topoisomerase I in the National
      Cancer Institute panel of human tumour cell lines.
AB  - Topoisomerase 1 (Top1), a nuclear enzyme involved in DNA relaxation, is the
      target of several anticancer drugs. TOP1 mutations occur in camptothecin
      resistant tumour cell lines. We explored, in the NCI panel of 60 human tumour
      cell lines, whether polymorphic variations in the TOP1 gene could explain
      differences in drug sensitivity. The 21 exons of the gene were fully studied as
      well as five intronic domains that had previously been shown to harbour single
      nucleotide polymorphisms (SNPs) or mutations. PCR products covering the whole
      exonic sequences or the relevant intronic domains were subjected to denaturing
      high-performance liquid chromatography. Nucleotide variations were then
      determined by sequencing. Discrimination between intronic common and variant
      homozygous samples was performed using a restriction fragment length polymorphism
      technique. Only one exonic mutation was detected, at the heterozygous state; it
      occurs in exon 19 of a colon cancer cell line (HCT-15) and consists of a G>A
      transition at position 75, resulting in a Met675Ile change. The intronic
      sequences studied harboured the SNPs expected with allelic frequencies between 20
      and 40%. Three major haplotypes, generating 92% of the 10 genotypes encountered,
      were defined as containing none of the intronic SNPs, or three of them, or all of
      them. No significant relationship was evidenced between Top1 expression and the
      TOP1 polymorphisms studied. However, when comparing the cytotoxicity of 138 drugs
      as a function of the genotypes, several drug groups, namely Top1 inhibitors,
      antifolates and taxanes, had significantly different IC(50)s as a function of the
      distribution of the intronic SNPs of the TOP1 gene.

PMID- 16983404
TI  - Diffraction-based determination of the phase modulation for general spatial light
      modulators.
AB  - We describe a characterization method based on diffraction for obtaining the
      phase response of spatial light modulators (SLMs), which in general exhibit both
      amplitude and phase modulation. Compared with the conventional interferometer
      based approach, the method is characterized by a simple setup that enables in
      situ measurements, allows for substantial mechanical vibration, and permits the
      use of a light source with a fairly low temporal coherence. The phase
      determination is possible even for a SLM with a full amplitude modulation depth,
      i.e., even if there are nulls in the amplitude transmission characteristic of the
      SLM. The method successfully determines phase modulation values in the full 2pi
      rad range with high accuracy. The experimental work includes comparisons with
      interferometer measurements as well as a SLM characterization with a light
      emitting diode (LED).

PMID- 16983403
TI  - Improving the outcome of patients with castration-resistant prostate cancer
      through rational drug development.
AB  - Castration-resistant prostate cancer (CRPC) is now the second most common cause
      of male cancer-related mortality. Although docetaxel has recently been shown to
      extend the survival of patients with CRPC in two large randomised phase III
      studies, subsequent treatment options remain limited for these patients. A
      greater understanding of the molecular causes of castration resistance is
      allowing a more rational approach to the development of new drugs and many new
      agents are now in clinical development. Therapeutic targets include the adrenal
      steroid synthesis pathway, androgen receptor signalling, the epidermal growth
      factor receptor family, insulin growth factor-1 receptor, histone deacetylase,
      heat shock protein 90 and the tumour vasculature. Drugs against these targets are
      giving an insight into the molecular pathogenesis of this disease and promise to
      improve patient quality of life and survival. Finally, the recent discovery of
      chromosomal translocations resulting in the upregulation of one of at least 3 ETS
      genes (ERG, ETV1, ETV4) may lead to novel agents for the treatment of this
      disease.

PMID- 16983405
TI  - Realizing any central projection with a mirror pair.
AB  - We show that, for any rotationally symmetric projection with a single virtual
      viewpoint, it is possible to design a two-mirror rotationally symmetric system
      that realizes the projection exactly. These mirror pairs are derived from two
      coupled differential equations. We give examples in which the projections from
      the sphere at infinity are stereographic, perspective, and equiresolution.

PMID- 16983406
TI  - Mosaic imaging with spatial light modulator technology.
AB  - Diffractive wavefront control with spatial light modulator technology has been
      successfully demonstrated both as a means of steering optical wavefronts and for
      compensating large optical aberrations. We describe the use of a spatial light
      modulator operating as a programmable diffractive optic to record extended-field
      of-view mosaic images centered about a large off-axis field angle. A gimbaled
      primary mirror allows the nominal viewing angle to be varied, and diffractive
      wavefront steering allows images to be acquired at discrete increments in the
      field angle about the nominal angle. Diffractive wavefront compensation corrects
      aberrations associated with the primary mirror orientation and changes in field
      angle introduced by diffractive wavefront steering. A time sequence of images
      recorded at discrete increments in the field angle is then digitally combined to
      create a high-pixel-count mosaic image. The effects of diffraction efficiency and
      wavelength-dependent wavefront errors on image quality are analyzed.

PMID- 16983407
TI  - Statistical adaptive sensing by detectors with spectrally overlapping bands.
AB  - It has recently been reported that by using a spectral-tuning algorithm, the
      photocurrents of multiple detectors with spectrally overlapping responsivities
      can be optimally combined to synthesize, within certain limits, the response of a
      detector with an arbitrary responsivity. However, it is known that the presence
      of noise in the photocurrent can degrade the performance of this algorithm
      significantly, depending on the choice of the responsivity spectrum to be
      synthesized. We generalize this algorithm to accommodate noise. The results are
      applied to quantum-dot mid-infrared detectors with bias-dependent spectral
      responses. Simulation and experiment are used to show the ability of the
      algorithm to reduce the adverse effect of noise on its spectral-tuning
      capability.

PMID- 16983408
TI  - Electrical-contact-free readout of the response of superconductive bolometer
      arrays using thermal cross talk.
AB  - We utilized and investigated the unique dependence of the magnitude and phase of
      the response on thermal cross talk between bolometer pixels in an array to
      measure the response of the devices through fewer monitoring devices. We show the
      feasibility of the proposed readout technique by use of two source pixels in an
      array, as the image-mapping devices, and one optically shielded pixel as the
      readout device. While the sensing pixels were electrical-contact free, the
      readout device was current biased in 4-probe current-bias configuration. Both the
      phase and the magnitude of the response due to the cross talk in the array were
      found to be strongly dependent on the modulation frequency and the distance
      between the sensing and the readout pixels. A series of measurements were
      designed to extract the response of each single-sensing pixel. By combining the
      measured data, the response of individual pixels could be extracted through the
      interpolation of the mapped responses.

PMID- 16983409
TI  - Commercial scale fabrication method for fabricating a gradient refractive-index
      rod: Overcoming volume shrinkage and chemical restrictions.
AB  - We report a fabrication method for a gradient refractive-index polymeric object
      from a binary comonomer system, regardless of the monomers' reactivity ratio and
      the molar volume criteria of gradient refractive-index development. To fabricate
      a large gradient refractive-index rod consisting of a methyl methacrylate and
      2,2,3,3-tetrafluoropropyl methacrylate comonomer pair that has not been used for
      fabrication of a copolymer gradient refractive-index rod by previous conventional
      methods because of chemical restrictions in molar volume and reactivity ratio
      difference, we use the so-called successive UV polymerization in a controlled
      radial volume in conjunction with an automatic refill reactor. Simultaneously and
      automatically, the volume shrinkage problem, an inevitable shortcoming for the
      fabrication of a large polymeric object in a commercial production scale, is
      overcome and exploited. The theoretical features of the refractive-index profile
      generation of this method are also compared with those of conventional methods
      for which the chemical restrictions of monomers are crucial for the shape of a
      refractive-index profile.

PMID- 16983410
TI  - Range gated active night vision system for automobiles.
AB  - Night vision for automobiles is an emerging safety feature that is being
      introduced for automotive safety. We develop what we believe is an innovative new
      night vision system using gated imaging principles. The concept of gated imaging
      is described and its basic advantages, including the backscatter reduction
      mechanism for improved vision through fog, rain, and snow. Evaluation of
      performance is presented by analyzing bar pattern modulation and comparing
      Johnson chart predictions.

PMID- 16983411
TI  - Imaging characteristics of a wavefront coding system with off-axis aberrations.
AB  - Imaging characteristics are analyzed for a wavefront coding system suffering from
      off-axis aberrations such as primary astigmatism and primary coma. Some
      analytical expressions for the optical transfer function are obtained by using
      the stationary-phase method. These expressions give the relationship between the
      optical transfer function and the off-axis aberrations. Some cases are computed
      and illustrated graphically. It is shown that the wavefront coding system has a
      high tolerance to primary astigmatism and a low sensitivity to primary coma.

PMID- 16983412
TI  - Self-mixing differential vibrometer based on electronic channel subtraction.
AB  - An instrument for noncontact measurement of differential vibrations is developed,
      based on the self-mixing interferometer. As no reference arm is available in the
      self-mixing configuration, the differential mode is obtained by electronic
      subtraction of signals from two (nominally equal) vibrometer channels, taking
      advantage that channels are servo stabilized and thus insensitive to speckle and
      other sources of amplitude fluctuation. We show that electronic subtraction is
      nearly as effective as field superposition. Common-mode suppression is 25-30 dB,
      the dynamic range (amplitude) is in excess of 100 microm, and the minimum
      measurable (differential) amplitude is 20 nm on a B = 10 kHz bandwidth. The
      instrument has been used to measure vibrations of two metal samples kept in
      contact, revealing the hysteresis cycle in the microslip and gross-slip regimes,
      which are of interest in the study of friction induced vibration damping of gas
      turbine blades for aircraft applications.

PMID- 16983413
TI  - Measurement of a low-absorption sample of OH-reduced fused silica.
AB  - Low-absorption optics made of OH-reduced fused silica are a key technology for
      future gravitational wave detectors such as the Advanced LIGO. We developed a
      sensitive method to measure the absorption inside the beam splitter of the GEO
      600, taking advantage of the effect of thermal lensing. Using this method, we
      derived a bulk absorption of less than 0.25 ppm/cm for a piece of Suprasil 311 SV
      at a wavelength of 1064 nm. To the best of our knowledge, this is the lowest
      value of light absorption inside fused silica reported so far in the literature.

PMID- 16983414
TI  - Hybrid normal-reverse prism coupler for light-emitting diode backlight systems.
AB  - For the first time to our knowledge, a hybrid normal-reverse prism coupler was
      formed on the bottom surface of a light guide in a LED backlight system to
      achieve a thin, lightweight, LED backlight system. The hybrid prism coupler (HPC)
      simultaneously exhibits two functions: extraction of guided light from the light
      guide and focusing the radiated light from the light guide, corresponding to the
      optical functions of the prism and diffusive sheets used in conventional LED
      backlight systems. Therefore, using a HPC eliminates the prism and diffusive
      sheets that have been indispensable optical elements in conventional LED
      backlight systems, which consequently reduces the thickness of the LED backlight
      system by 40% compared with conventional systems.

PMID- 16983415
TI  - Optical configuration of a horizontal-switching liquid-crystal cell for
      improvement of the viewing angle.
AB  - We propose an optical configuration of a horizontal-switching liquid-crystal
      cell, consisting of a splayed liquid-crystal cell and uniaxial films, to improve
      the viewing angle characteristics by compensating for the phase dispersion in a
      diagonal direction. The optical design of the proposed configuration was
      performed on a Poincare sphere with geometric calculations. By fabricating in
      plane switching cells with the introduced configuration, we demonstrated their
      optical performances. As a result, we found that the diagonal viewing angle of
      the proposed horizontal-switching cell could be increased by 80% compared to a
      symmetrical viewing cone.

PMID- 16983416
TI  - Optically tunable guided-mode resonance filter.
AB  - We have demonstrated a guided-mode resonance filter (GMRF) whose properties are
      tunable with laser illumination through the incorporation of a nonlinear dye.
      Laser illumination causes a change in the refractive index of the dye-doped
      portion of the structure, leading to controlled tuning of the GMRF reflectance
      spectrum. Changes in the refractive index of dye-doped regions are proportional
      to the intensity of the incident laser beam and are as high as Delta n = 0.09.
      The reflectance tuning effect occurs on a time scale of many seconds and is
      completely reversible upon termination of the laser illumination.

PMID- 16983417
TI  - Surface plasmon resonance sensors based on uniform-waist tapered fibers in a
      reflective configuration.
AB  - We present a configuration for surface plasmon resonance sensors based on uniform
      waist tapered optical fibers and reflective elements. Once the fiber is tapered
      fulfilling the adiabatic criterion, a multilayer including a metallic medium is
      asymmetrically deposited on the uniform waist of the fiber. This feature provides
      the resonant excitation of multiple surface plasma waves. In addition, a mirror
      is produced at the fiber tip by a chemical Tollens reaction. In this way, the
      sensor operates in a reflective mode, more convenient for dip probes. When these
      sensors are spectrally interrogated, a high sensitivity of 10-4 refractive index
      units per nanometer is attained. These devices can be advantageously used for any
      kind of chemical sensing and biosensing.

PMID- 16983418
TI  - Single-particle evanescent light scattering simulations for total internal
      reflection microscopy.
AB  - We simulate and measure light scattering of a micrometer-sized spherical particle
      suspended in solution close to a glass substrate. The model, based on the
      discrete sources method, is developed to describe the experimental situation of
      total internal reflection microscopy experiments; i.e., the particle is
      illuminated by an evanescent light field originating from the glass-solvent
      interface. In contrast to the well-established assumption of a simple exponential
      decay of the scattering intensity with distance, we demonstrate significant
      deviations for a certain range of penetration depths and polarization states of
      the incident light.

PMID- 16983419
TI  - Interferometric tracking of optically trapped probes behind structured surfaces:
      A phase correction method.
AB  - We investigate the influence of an additional scatterer on the tracking signal of
      an optically trapped particle. The three-dimensional particle position is
      recorded interferometrically with nanometer precision by using a quadrant
      photodiode in the back focal plane of a detection lens. A phase disturbance
      underneath the sample leads to incorrect position signals. The resulting
      interaction potential and forces are therefore erroneous as well. We present a
      procedure to correct for the disturbance by measuring its interferometric signal.
      We prove the applicability of our phase correction approach by generating a
      defined displacement of the trapped probe.

PMID- 16983420
TI  - Toward resistant vacuum-ultraviolet coatings for free-electron lasers down to 150
      nm.
AB  - Research and development are currently trying to run a storage ring free-electron
      laser down to 150 nm with robust optics. Vacuum-ultraviolet fluoride optics with
      protected oxide layers and enhanced metallic mirrors are investigated.

PMID- 16983421
TI  - Microstructure of magnesium fluoride films deposited by boat evaporation at 193
      nm.
AB  - Single layer magnesium fluoride (MgF2) was deposited on fused-silica substrates
      by a molybdenum boat evaporation process at 193 nm. The formation of various
      microstructures in relation to the different substrate temperatures and
      deposition rates were investigated. The relation between these microstructures
      (including cross-sectional morphology, surface roughness, and crystalline
      structures), the optical properties (including refractive index and optical loss)
      and stress, were all investigated. It was found that the laser-induced damage
      threshold (LIDT) would be affected by the microstructure, optical loss, and
      stress of the thin film. To obtain a larger LIDT value and better optical
      characteristics, MgF2 films should be deposited at a high substrate temperature
      (300 degrees C) and at a low deposition rate (0.05 nm s(-1)).

PMID- 16983422
TI  - Joint transform correlator with spatial code division multiplexing.
AB  - A joint transform correlator may suffer from overlapping of the zero diffraction
      order of the output, which does not contain relevant information, and the
      correlation peaks that appear in the first diffraction orders if objects are not
      sufficiently separated. Such overlapping significantly reduces the signal-to
      noise ratio of the identification process. We propose a novel approach based on
      code division multiplexing technique in which the contrast of the identification
      peaks is significantly enhanced. The approach does not include placing the two
      objects side by side but rather includes code multiplexing them. Moreover, the
      code division multiplexing technique allows the space-bandwidth product to be
      improved. Optical implementation results are given.

PMID- 16983423
TI  - Viewing angle enhancement for two- and three-dimensional holographic displays
      with random superresolution phase masks.
AB  - Holographic displays employing binary phase modulation have been demonstrated to
      be attractive on the grounds of efficiency and miniaturization, and they offer a
      plausible approach to two-dimensional (2D) and three-dimensional (3D) image
      projection and display. A novel algorithm--one-step phase retrieval--and
      corresponding hardware architecture have recently been proposed, providing the
      performance required for real-time holographic display. However, since viewing
      angle varies inversely with pixel size, very small display pixels are required to
      achieve a wide field of view. This is particularly problematic for 3D displays,
      as the requirement for a large display with small pixels has hitherto
      necessitated an unachievably large electrical bandwidth. We present a novel
      approach, utilizing fixed random pixelated quaternary phase masks of greater
      resolution than the displayed hologram, to dramatically increase the viewing
      angle for 2D and 3D holographic displays without incurring a bandwidth penalty or
      significantly degrading image quality. Furthermore, an algorithm is presented to
      generate holograms accounting for the presence of such a phase mask, so that only
      one mask is required.

PMID- 16983424
TI  - Multiframe blind deconvolution of heavily blurred astronomical images.
AB  - A multichannel blind deconvolution algorithm that incorporates the maximum
      likelihood image restoration by several estimates of the differently blurred
      point-spread function (PSF) into the Ayers-Dainty iterative algorithm is
      proposed. The algorithm uses no restrictions on the image and the PSFs except for
      the assumption that they are positive. The algorithm employs no cost functions,
      input parameters, a priori probability distributions, or the analytically
      specified transfer functions. The iterative algorithm permits its application in
      the presence of different kinds of distortion. The work presents results of
      digital modeling and the results of processing real telescope data from several
      satellites. The proof of convergence of the algorithm to the positive estimates
      of object and the PSFs is given. The convergence of the Ayers-Dainty algorithm
      with a single processed frame is not obvious in the general case; therefore it is
      useful to have confidence in its convergence in a multiframe case. The dependence
      of convergence on the number of processed frames is discussed. Formulas for
      evaluating the quality of the algorithm performance on each iteration and the
      rule of stopping its work in accordance with this quality are proposed. A method
      of building the monotonically converging subsequence of the image estimates of
      all the images obtained in the iterative process is also proposed.

PMID- 16983425
TI  - Collaborative multihop transmission of distributed sensor imagery.
AB  - We consider a network of imaging sensors. We address the problem of energy
      efficient communication of the measurements of the sensors. A novel algorithm is
      presented for the purpose of exploiting intersensor and intrasensor correlation,
      which is inherent in a network of imaging sensors. The collaborative algorithm is
      used in conjunction with a cooperative multihop routing strategy to maximize the
      lifetime of the network. The algorithm is demonstrated to achieve an average gain
      in the lifetime as high as 3.2 over previous methods.

PMID- 16983426
TI  - Integrated approach for automatic target recognition using a network of
      collaborative sensors.
AB  - We introduce what is believed to be a novel concept by which several sensors with
      automatic target recognition (ATR) capability collaborate to recognize objects.
      Such an approach would be suitable for netted systems in which the sensors and
      platforms can coordinate to optimize end-to-end performance. We use correlation
      filtering techniques to facilitate the development of the concept, although other
      ATR algorithms may be easily substituted. Essentially, a self-configuring
      geometry of netted platforms is proposed that positions the sensors optimally
      with respect to each other, and takes into account the interactions among the
      sensor, the recognition algorithms, and the classes of the objects to be
      recognized. We show how such a paradigm optimizes overall performance, and
      illustrate the collaborative ATR scheme for recognizing targets in synthetic
      aperture radar imagery by using viewing position as a sensor parameter.

PMID- 16983427
TI  - Multidirectional curved integral imaging with large depth by additional use of a
      large-aperture lens.
AB  - We propose a curved integral imaging system with large depth achieved by the
      additional use of a large-aperture lens in a conventional large-depth integral
      imaging system. The additional large-aperture lens provides a multidirectional
      curvature effect and improves the viewing angle. The proposed system has a simple
      structure due to the use of well-fabricated, unmodified flat devices. To
      calculate the proper elemental images for the proposed system, we explain a
      modified computer-generated pickup technique based on an ABCD matrix and analyze
      an effective viewing zone in the proposed system. From experiments, we show that
      the proposed system has an improved viewing angle of more than 7 degrees compared
      with conventional integral imaging.

PMID- 16983428
TI  - Feature-specific structured imaging.
AB  - We present a feature-specific imaging system based on the use of structured
      light. Feature measurements are obtained by projecting spatially structured
      illumination onto an object and collecting all the reflected light onto a single
      photodetector. Principal component features are used to define the illumination
      patterns. The optimal linear minimum mean-square error (LMMSE) operator is used
      to generate object estimates from the measured features. We study the optimal
      allocation of illumination energy into each feature measurement in the presence
      of additive white Gaussian detector noise and optical blur. We demonstrate that
      this new imaging approach reduces imager complexity and provides improved image
      quality in high noise environments. Compared to the optimal LMMSE postprocessing
      of a conventional image, feature-specific structured imaging provides a 38% rms
      error reduction and requires 400 times fewer measurements for a noise standard
      deviation of sigma = 2 x 10(-3). Experimental results validate these theoretical
      predictions.

PMID- 16983429
TI  - Performance evaluation of partial differential equation models in electronic
      speckle pattern interferometry and the delta-mollification phase map method.
AB  - The ordinary differential equation (ODE) and partial differential equation (PDE)
      image- processing methods have been applied to reduce noise and enhance the
      contrast of electronic speckle pattern interferometry fringe patterns. We
      evaluate the performance of a few representative PDE denoising models
      quantitatively with two parameters called image fidelity and speckle index, and
      then we choose a good denoising model. Combining this denoising model with the
      ODE enhancement method, we make it possible to perform contrast enhancement and
      denoising simultaneously. Second, we introduce the delta-mollification method to
      smooth the unwrapped phase map. Finally, based on PDE image processing, delta
      mollification and some traditional techniques, an approach of phase extraction
      from a single fringe pattern is tested for computer-simulated and experimentally
      obtained fringe patterns. The method works well under a high noise level and
      limited visibility and can extract accurate phase values.

PMID- 16983430
TI  - Iterative soft-minimum mean-square error equalization for digital nonlinear page
      oriented memories.
AB  - Digital page-oriented volume holographic memory (POVHM) is a promising candidate
      for next-generation ultrahigh capacity optical data storage technology. As the
      capacity of the POVHMs increases, the bit error rate performance of the system is
      degraded due to increased interpixel interference (IPI) and noise. To improve the
      system performance under these adverse effects and to increase the capacity,
      joint iterative soft equalization-detection and error correction decoding might
      be attractive. To address that, by considering the nonlinearity inherent in the
      channel, an iterative soft equalization method that is optimized in the minimum
      mean-square error (MMSE) sense, called the iterative soft-MMSE (ISMMSE)
      equalization, is devised. The performance of the ISMMSE is evaluated by use of
      numerical experiments under different amounts of IPI and optical noise.
      Simulation results suggest that the ISMMSE is a good candidate for an ultrahigh
      capacity POVHM, which employs joint iterative equalization-detection and
      decoding.

PMID- 16983432
TI  - Retrieval of aerosol properties from combined multiwavelength lidar and
      sunphotometer measurements.
AB  - Simulation studies were carried out with regard to the feasibility of using
      combined observations from sunphotometer (SPM) and lidar for microphysical
      characterization of aerosol particles, i.e., the retrieval of effective radius,
      volume, and surface-area concentrations. It was shown that for single,
      homogeneous aerosol layers, the aerosol parameters can be retrieved with an
      average accuracy of 30% for a wide range of particle size distributions. Based on
      the simulations, an instrument combination consisting of a lidar that measures
      particle backscattering at 355 and 1574 nm, and a SPM that measures at three to
      four channels in the range from 340 to 1020 nm is a promising tool for aerosol
      characterization. The inversion algorithm has been tested for a set of
      experimental data. The comparison with the particle size distribution parameters,
      measured with in situ instrumentation at the lidar site, showed good agreement.

PMID- 16983431
TI  - Bio-optical properties and ocean color algorithms for coastal waters influenced
      by the Mississippi River during a cold front.
AB  - During the passage of a cold front in March 2002, bio-optical properties examined
      in coastal waters impacted by the Mississippi River indicated that westward
      advective flows and increasing river discharge containing high concentrations of
      nonalgal particles contributed significantly to surface optical variability. A
      comparison of seasonal data from three cruises indicated spectral models of
      absorption and scattering to be generally consistent with other coastal
      environments, while their parameterization in terms of chlorophyll (Chl) alpha
      concentration showed seasonal variability. The exponential slope of the colored
      dissolved organic matter (CDOM) averaged 0.0161+/-0.00054 nm(-1) and nonalgal
      absorption averaged 0.011 nm(-1) with deviations from general trends observed due
      to anomalous water properties. Although the phytoplankton specific absorption
      coefficients varied over a wide range [0.02 to 0.1 m2 (mg Chl)(-1) at 443 nm]
      being higher in offshore surface waters, values of phytoplankton absorption
      spectra at the Sea-Viewing Wide Field-of-View Sensor (SeaWiFS) wave bands were
      highly correlated to modeled values. Particulate scattering characteristics were
      similar to observations for other coastal waters, while backscattering ratios
      were on average lower in phytoplankton-dominated surface waters (0.011+/-0.003)
      and higher in low Chl near-bottom waters (0.0191+/-0.0045). Average percent
      differences in remote sensing reflectance Rrs derived from modeled and in-water
      radiometric measurements were highest in the blue wave bands (52%) and at
      locations with more stratified water columns. SeaWiFS estimates of Chl and CDOM
      absorption derived using regional empirical algorithms were highly correlated to
      in situ data.

PMID- 16983433
TI  - Analytical solution of radiative transfer in the coupled atmosphere-ocean system
      with a rough surface.
AB  - Using the computationally efficient discrete-ordinate method, we present an
      analytical solution for radiative transfer in the coupled atmosphere-ocean system
      with a rough air-water interface. The theoretical formulations of the radiative
      transfer equation and solution are described. The effects of surface roughness on
      the radiation field in the atmosphere and ocean are studied and compared with
      satellite and surface measurements. The results show that ocean surface roughness
      has significant effects on the upwelling radiation in the atmosphere and the
      downwelling radiation in the ocean. As wind speed increases, the angular domain
      of sunglint broadens, the surface albedo decreases, and the transmission to the
      ocean increases. The downward radiance field in the upper ocean is highly
      anisotropic, but this anisotropy decreases rapidly as surface wind increases and
      as ocean depth increases. The effects of surface roughness on radiation also
      depend greatly on both wavelength and angle of incidence (i.e., solar elevation);
      these effects are significantly smaller throughout the spectrum at high Sun. The
      model-observation discrepancies may indicate that the Cox-Munk surface roughness
      model is not sufficient for high wind conditions.

PMID- 16983434
TI  - Regularized inversion method for retrieval of aerosol particle size distribution
      function in W(1,2) space.
AB  - A determination of the aerosol particle size distribution function by using the
      particle spectrum extinction equation is an ill-posed integral equation of the
      first kind. To overcome this, we must incorporate regularization techniques. Most
      of the literature focuses on the Phillips-Twomey regularization or its
      variations. However, there are drawbacks for some applications in which the real
      aerosol distributions have large oscillations in a Junge-type distribution. The
      reason for this is that the scale matrix based on the norm of the second
      differences in the Phillips-Twomey regularization is too ill- conditioned to
      filter the large perturbations induced by the small algebraic spectrum of the
      kernel matrix and the additive noise. Therefore we reexamine the aerosol particle
      size distribution function retrieval problem and solve it in W1,2 space. This
      setting is based on Sobolev's embedding theorem in which the approximate solution
      best simulates the true particle size distribution functions. For choosing the
      regularization parameters, we also develop an a posteriori parameter choice
      method, which is based on the discrepancy principle. Our numerical results are
      based on the remote sensing data measured by the CE318 sunphotometer in Jia Xiang
      County, Shan Dong Province, China, and are performed to show the feasibility of
      the proposed algorithms.

PMID- 16983435
TI  - Characteristics of dust aerosols inferred from lidar depolarization measurements
      at two wavelengths.
AB  - Lidar depolarization measurements were performed simultaneously at two
      wavelengths (532 and 1064 nm) in an Asian dust event. The observed particle
      depolarization ratio for 1064 nm was generally larger than that for 532 nm, and
      it was found that the mixing of Asian dust and other spherical aerosols must be
      taken into account. A simple two-component theory considering two types of
      aerosol (dust and spherical aerosols) was developed and applied to the observed
      data. The mixing ratio of dust and the backscatter-related Angstrom exponents for
      dust and spherical aerosols was derived. These parameters can be used to infer
      characteristics of the aerosols and the mixed states.

PMID- 16983436
TI  - Combined Henyey-Greenstein and Rayleigh phase function.
AB  - The phase function is an important parameter that affects the distribution of
      scattered radiation. In Rayleigh scattering, a scatterer is approximated by a
      dipole, and its phase function is analytically related to the scattering angle.
      For the Henyey-Greenstein (HG) approximation, the phase function preserves only
      the correct asymmetry factor (i.e., the first moment), which is essentially
      important for anisotropic scattering. When the HG function is applied to small
      particles, it produces a significant error in radiance. In addition, the HG
      function is applied only for an intensity radiative transfer. We develop a
      combined HG and Rayleigh (HG-Rayleigh) phase function. The HG phase function
      plays the role of modulator extending the application of the Rayleigh phase
      function for small asymmetry scattering. The HG-Rayleigh phase function
      guarantees the correct asymmetry factor and is valid for a polarization radiative
      transfer. It approaches the Rayleigh phase function for small particles. Thus the
      HG-Rayleigh phase function has wider applications for both intensity and
      polarimetric radiative transfers. For microwave radiative transfer modeling in
      this study, the largest errors in the brightness temperature calculations for
      weak asymmetry scattering are generally below 0.02 K by using the HG-Rayleigh
      phase function. The errors can be much larger, in the 1-3 K range, if the
      Rayleigh and HG functions are applied separately.

PMID- 16983437
TI  - Cross-linkable bromo-fluorinated poly(arylene ether ketone)s for photonic device
      applications.
AB  - A series of novel cross-linkable bromo-fluorinated poly(arylene ether ketone)s
      have been synthesized and used to fabricate photonic devices. The polymers,
      prepared by polycondensation reactions of decafluorobenzophenone with mixtures of
      bisphenols in different ratios, exhibit excellent solubility in common organic
      solvents and can be easily cast into optical-quality thin films by spin coating.
      The materials are thermally stable with decomposition temperatures (Td, 5% weight
      loss) over 450 degrees C and have high glass transition temperatures (Tg) in the
      range of 164 degrees C-178 degrees C. By controlling the bromine content of the
      polymers, the refractive index can be precisely controlled over a range as wide
      as 0.07. The material has excellent design flexibility, low optical loss (0.4-0.6
      dB/cm at 1550 nm), a low birefringence (2-3 x 10(-3)), and is suitable for use in
      wavelength sensitive photonic devices based on arrayed waveguide gratings.

PMID- 16983438
TI  - Nanocrystals of PbSe core, PbSe/PbS, and PbSe/PbSxS(1-x) core/shell as saturable
      absorbers in passively Q-switched near-infrared lasers.
AB  - The saturable optical absorption properties of PbSe core nanocrystals (NCs), and
      their corresponding PbSe/PbScore/shell and PbSe/PbSexS(1-x) core/alloyed-shell
      NCs, were examined at lambda = 1.54 microm. Saturation intensities of
      approximately 100 MW/cm2 were obtained. The NCs act as passive Q switches in near
      infrared pulsed lasers. Q-switched output pulse energies up to 3 mJ, with a pulse
      duration of 40-55 ns were demonstrated. Analysis of the optical transmission
      versus pulse light intensity was carried out according to a model that includes
      ground-state as well as excited-state absorption. For pulses approximately 10 ns
      long, the NCs act as fast saturable absorbers. The theoretical fits yield a
      ground-state absorption cross section of 10-16-10-15 cm2, an excited-state
      absorption cross section of sigma(es) is congruent to 10(-16) cm2, and an
      effective lifetime of tau(eff) is congruent to 5 x 10(-12) s.

PMID- 16983439
TI  - Optical sensors based on III-nitride photodetectors for flame sensing and
      combustion monitoring.
AB  - Combustion control requires visible photodetectors to sense the CH* CL emission
      at 430 nm that combined with a visible-blind UV photodetector allows us to obtain
      the OH*/CH* ratio. UV-visible P-InGaN/GaN multiple quantum well-N photodiodes
      with 15-18 mm2 areas were fabricated to conduct OH* (308 nm) and CH* CL detection
      without external filters. Bandpass detectors at 230-390 nm and 360-450 nm
      presented linear responses over five decades and rejection ratios >10(3) at 430
      and 308 nm, respectively. A full optical sensor system was built and detectors
      operated at 120 degrees C in a combustion chamber, showing linear responses
      within the dynamic range, maximum signal-to-noise ratios of 103 and response
      times of <1 s. An exponential association dependence between the optical OH*/CH*
      CL signals and the gas/air ratios was found.

PMID- 16983440
TI  - Concurrent multiaxis differential optical absorption spectroscopy system for the
      measurement of tropospheric nitrogen dioxide.
AB  - The development of a new concurrent multiaxis (CMAX) sky viewing spectrometer to
      monitor rapidly changing urban concentrations of nitrogen dioxide is detailed.
      The CMAX differential optical absorption spectroscopy (DOAS) technique involves
      simultaneous spectral imaging of the zenith and off-axis measurements of
      spatially resolved scattered sunlight. Trace-gas amounts are retrieved from the
      measured spectra using the established DOAS technique. The potential of the CMAX
      DOAS technique to derive information on rapidly changing concentrations and the
      spatial distribution of NO2 in an urban environment is demonstrated. Three
      example data sets are presented from measurements during 2004 of tropospheric NO2
      over Leicester, UK (52.62 degrees N, 1.12 degrees W). The data demonstrate the
      current capabilities and future potential of the CMAX DOAS method in terms of the
      ability to measure real-time spatially disaggregated urban NO2.

PMID- 16983441
TI  - Fabrication and characterization of microstructures with optical quality surfaces
      in fused silica glass using femtosecond laser pulses and chemical etching.
AB  - We present a study of the sidewall surface quality inside microchannels
      fabricated in fused silica glass by femtosecond laser pulses and chemical
      etching. Multiple combinations of laser exposure and etching solution parameters
      were examined. Results of scanning electron microscopy, atomic force microscopy,
      and optical reflection analyses of the surfaces are presented. The results
      obtained demonstrate the feasibility of optical quality surface fabrication,
      which in turn demonstrates the feasibility of fabricating complex integrated
      devices containing microfluidic channels and optical waveguides in the glass
      substrates.

PMID- 16983442
TI  - Simple pulse compression scheme based on filtering self-phase modulation
      broadened spectrum and its application in an optical time-division multiplexing
      system.
AB  - We propose a simple and stable pulse compression scheme based on a filtering self
      phase modulation broadened spectrum in a highly nonlinear fiber. It is found
      experimentally that under offset filtering the compressed pulse has a better
      quality compared with center filtering, such as a no pulse pedestal. Furthermore,
      numerical simulations reveal that the scheme has the potential to improve the
      pulse extinction ratio during compression. Finally, based on the obtained pulse
      train the 4 x 10 Gbits/s optical time-division multiplexing system is studied for
      verification of the high pulse quality. The compression scheme has the advantages
      of simple configuration, being pedestal-free, and having a high pulse extinction
      ratio.

PMID- 16983443
TI  - Simultaneous extraction of optical transport parameters and intrinsic
      fluorescence of tissue mimicking model media using a spatially resolved
      fluorescence technique.
AB  - We present a method based on spatially resolved fluorescence measurement for the
      simultaneous estimation of optical transport parameters, namely, the reduced
      scattering coefficient (micro s'), the absorption coefficient (micro a), and the
      intrinsic fluorescence spectra from turbid media. The accuracy of this approach
      was tested by conducting studies on a series of tissue-simulating phantoms with
      known optical transport properties. The estimated relative error in the values
      for micro s' and micro a using this technique was found to be < or =10%.
      Furthermore, the line shape and intensity of the intrinsic fluorescence recovered
      by using this approach were observed to be free from the distorting effects of
      the wavelength-dependent absorption and scattering properties of the medium, and
      they were in excellent agreement with the directly measured intrinsic
      fluorescence spectra of the fluorophores.

PMID- 16983444
TI  - Fiber-optic fluorescence correlation spectrometer.
AB  - Fluorescence correlation spectroscopy (FCS) is a sensitive technique used to
      probe size, concentration, flow velocity, and reaction kinetics in a dilute
      solution. Conventional FCS spectrometers achieve this sensitivity at the cost of
      using bulky optics. We demonstrate a technique that utilizes a single-mode
      optical fiber of 3.3 microm mode field diameter to perform FCS measurements. We
      demonstrate that the technique has adequate sensitivity to perform FCS
      measurements on fluorescent beads of 13 nm radius, and that the results agree
      with theoretical predictions. Our method potentially allows FCS to be extended to
      remote and in vivo applications.

PMID- 16983445
TI  - Action plans in asthma.
AB  - BACKGROUND: Action plans are recommended for most patients with persistent asthma
      to reduce the morbidity associated with this chronic disease. Unfortunately,
      despite these recommendations, this tool remains underused. METHODS: The authors
      conducted a descriptive study at the asthma clinic of a tertiary care centre to
      determine the number of asthmatic patients presenting to a respiratory physician
      (new reference or follow-up visit) who possessed an individualized, written
      action plan, and to evaluate the patients' level of confidence and perceived
      efficacy toward their plans. In addition, for all patients in the study, the
      level of confidence in and the perceived efficacy of three different action plans
      (two traditional tools versus a simplified tool) were compared. RESULTS: A total
      of 92 asthmatic patients were included in the study. Overall, 46% of the patients
      possessed an action plan. The patients' average level of confidence and perceived
      efficacy toward their action plans were high (4.1 out of five and 3.3 out of
      four, respectively). When the three different action plans were compared, the
      level of confidence in and perceived efficacy of the traditional tools were
      similar, both being superior to the simplified tool. CONCLUSION: The number of
      asthmatic patients who presented to the asthma clinic and who possessed an action
      plan was higher than the reported Canadian mean of 10%; however, most of the
      patients were treated by specialized respiratory physicians, which may explain
      this improvement. Considering that most patients with persistent asthma should
      have an individualized, written action plan, the present study confirms that this
      tool is still not used for all asthmatic patients.

PMID- 16983446
TI  - The value of thoracic computed tomography scans in clinical diagnosis: a
      prospective study.
AB  - BACKGROUND: Computed tomography (CT) scans are used extensively to investigate
      chest disease because of their cross-sectional perspective and superior contrast
      resolution compared with chest radiographs. These advantages lead to a more
      accurate imaging assessment of thoracic disease. The actual use and evaluation of
      the clinical impact of thoracic CT has not been assessed since scanners became
      widely available. OBJECTIVE: To identify patterns of utilization, waiting times
      and the impact of CT scan results on clinical diagnoses. DESIGN: A before and
      after survey of physicians who had ordered thoracic CT scans. SETTING: Vancouver
      General Hospital--a tertiary care teaching centre in Vancouver, British Columbia.
      SUBJECTS: Physicians who had ordered CT scans. INTERVENTION: Physicians completed
      a standard questionnaire before and after the CT scan result was available.
      MEASUREMENTS: Changes in the clinical diagnosis, estimates of the probabilities
      for the diagnosis both before and after the CT scan, and waiting times. RESULTS:
      Four hundred fifty-four thoracic CT cases had completed questionnaires, of whom
      80% were outpatients. A change in diagnosis was made in 48% of cases (25% with a
      normal CT scan and 23% with CT scan findings that indicated a different
      diagnosis). The largest change in probability scores for the clinical diagnosis
      before and after the CT scan was 43.9% for normal scans, while it was 36.3% for a
      different diagnosis and 26.3% for the same diagnosis. High-priority scans were
      associated with decreased waiting time (--7.89 days for each unit increase in
      priority). CONCLUSIONS: The CT scan results were associated with a change in
      diagnosis in 48% of cases. Normal scans constituted 25% of the total and had the
      greatest impact scores. Waiting times were highly correlated with increased
      urgency of the presenting problem.

PMID- 16983447
TI  - Factors associated with length of stay in hospital for suspected community
      acquired pneumonia.
AB  - OBJECTIVE: To determine factors associated with the length of stay (LOS) for
      patients with suspected community-acquired pneumonia (CAP) who required
      hospitalization for treatment. STUDY DESIGN: The authors studied a population
      based prospective cohort of 2,757 adults with suspected CAP who were admitted
      over a two-year period. Logistic regression, multiple linear regression, and
      classification and regression trees were used to determine the factors associated
      with LOS. SETTING: The study was conducted in two community and tertiary care
      hospitals, two community and secondary care hospitals, and two community
      hospitals in the Capital Health Region of Edmonton, Alberta. RESULTS: Symptoms
      such as sweats, shaking chills and wheezing were associated with an LOS of seven
      days or shorter, whereas weight loss, functional impairment, heart, renal or
      neoplastic diseases and time to first dose of antibiotic were predictive of an
      LOS greater than seven days. Regression tree analysis indicated that rapid
      achievement of physiological stability was associated with a shorter LOS. The use
      of an indwelling urinary catheter was found to be an important determinant of
      LOS. CONCLUSIONS: The present study found several new associations with increased
      LOS in patients with CAP, including functional status, time to receipt of first
      dose of antibiotic therapy, use of certain antibiotics, presence of a urinary
      catheter and the importance of time to physiological stability. An intervention
      targeting avoidance of urinary catheters may be associated with a shorter LOS.

PMID- 16983449
TI  - Review of scalp alopecia due to a clinically unapparent or minimally apparent
      neoplasm (SACUMAN).
AB  - Neoplastic cells, both malignant and benign, local occurring and metastatic, can
      cause alopecia of the scalp. However, the infiltration of neoplastic cells is
      sometimes not florid; a condition known as "scalp alopecia due to a clinically
      unapparent or minimally apparent neoplasm" (SACUMAN). Neoplastic cells can
      nevertheless destroy hair follicles by inducing fibroplasias via inflammatory
      mediators, attracting inflammatory cells and/or replacing normal cellular
      populations. The infiltrative nature of such an alopecia can be unapparent or
      only minimally apparent. The most common neoplasm in which an uncomplicated,
      minimally or unapparent scalp alopecia occurs and no infiltrate of cancer is
      suspected is metastatic breast carcinoma. Other causes include squamous and basal
      cell carcinomas, angiosarcoma, gastric carcinoma, placental site tromphoblastic
      tumor, and mycosis fungoides. Syringoma-like proliferations can underlie
      alopecia. It is unclear whether these proliferations are true syringomas or
      normal findings. In conclusion, neoplasms causing cicatricial alopecia of the
      scalp are very rare, so generalizations from the limited number of case reports
      are of uncertain importance. Moreover, it is likely that many cases of neoplasms
      causing cicatricial alopecia of the scalp are diagnosed as inflammatory alopecia
      and not neoplasms, thus depriving us of a full accounting and understanding of
      this entity. Dermatologists must be aware that in rare cases a bland scalp
      alopecia can represent a new or recurring, local or metastatic neoplasm.

PMID- 16983448
TI  - Mucin overproduction in chronic inflammatory lung disease.
AB  - Mucus overproduction and hypersecretion are commonly observed in chronic
      inflammatory lung disease. Mucins are gel-forming glycoproteins that can be
      stimulated by a variety of mediators. The present review addresses the mechanisms
      involved in the upregulation of secreted mucins. Mucin induction by neutrophil
      elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis
      transmembrane conductance regulator malfunction are also discussed.

PMID- 16983450
TI  - Agrobacterium tumefaciens mediated transfer of Phaseolus vulgaris alpha-amylase
      inhibitor-1 gene into mungbean Vigna radiata (L.) Wilczek using bar as selectable
      marker.
AB  - Morphologically normal and fertile transgenic plants of mungbean with two
      transgenes, bar and alpha-amylase inhibitor, have been developed for the first
      time. Cotyledonary node explants were transformed by cocultivation with
      Agrobacterium tumefaciens strain EHA105 harboring a binary vector pKSB that
      carried bialaphos resistance (bar) gene and Phaseolus vulgaris alpha-amylase
      inhibitor-1 (alphaAI-1) gene. Green transformed shoots were regenerated and
      rooted on medium containing phosphinothricin (PPT). Preculture and wounding of
      the explants, presence of acetosyringone and PPT-based selection of transformants
      played significant role in enhancing transformation frequency. Presence and
      expression of the bar gene in primary transformants was evidenced by PCR-Southern
      analysis and PPT leaf paint assay, respectively. Integration of the Phaseolus
      vulgaris alpha-amylase inhibitor gene was confirmed by Southern blot analysis.
      PCR analysis revealed inheritance of both the transgenes in most of the T(1)
      lines. Tolerance to herbicide was evidenced from seed germination test and
      chlorophenol red assay in T(1) plants. Transgenic plants could be recovered after
      8-10 weeks of cocultivation with Agrobacterium. An overall transformation
      frequency of 1.51% was achieved.

PMID- 16983451
TI  - Heterosynaptic modulation of the dorsal root potential in the turtle spinal cord
      in vitro.
AB  - In the somatosensory system, the flow of sensory information is regulated at
      early stages by presynaptic inhibition. Recent findings have shown that the
      mechanisms generating the primary afferent depolarization (PAD) associated with
      presynaptic inhibition are complex, with some components mediated by a non
      spiking mechanism. How sensory inputs carried by neighbouring afferent fibres
      interact to regulate the generation of PAD, and thus presynaptic inhibition, is
      poorly known. Here, we investigated the interaction between neighbouring primary
      afferents for the generation of PAD in an in vitro preparation of the turtle
      spinal cord. To monitor PAD we recorded the dorsal root potential (DRP), while
      the simultaneous cord dorsum potential (CDP) was recorded to assess the
      population postsynaptic response. We found that the DRP and the CDP evoked by a
      primary afferent test stimulus was greatly reduced by a conditioning activation
      of neighbouring primary afferents. This depression had early and late components,
      mediated in part by GABAA and GABAB receptors, since they were reduced by
      bicuculline and SCH 50911 respectively. However, with the selective stimulation
      of C and Adelta fibres in the presence of TTX, the early and late depression of
      the DRP was replaced by facilitation of the GABAergic and glutamatergic
      components of the TTX-resistant DRP. Our findings suggest a subtle lateral
      excitatory interaction between primary afferents for the generation of PAD
      mediated by a non-spiking mechanism that may contribute to shaping of information
      transmitted by C and Adelta fibres in a spatially confined scale in analogy with
      the retina and olfactory bulb.

PMID- 16983453
TI  - Plant dehydrins--tissue location, structure and function.
AB  - Dehydrins (DHNs) are part of a large group of highly hydrophilic proteins known
      as LEA (Late Embryogenesis Abundant). They were originally identified as group II
      of the LEA proteins. The distinctive feature of all DHNs is a conserved, lysine
      rich 15-amino acid domain, EKKGIMDKIKEKLPG, named the K-segment. It is usually
      present near the C-terminus. Other typical dehydrin features are: a track of Ser
      residues (the S-segment); a consensus motif, T/VDEYGNP (the Y-segment), located
      near the N-terminus; and less conserved regions, usually rich in polar amino
      acids (the Phi-segments). They do not display a well-defined secondary structure.
      The number and order of the Y-, S-and K-segments define different DHN sub
      classes: Y(n)SK(n), Y(n)Kn, SK(n), K(n) and K(n)S. Dehydrins are distributed in a
      wide range of organisms including the higher plants, algae, yeast and
      cyanobacteria. They accumulate late in embryogenesis, and in nearly all the
      vegetative tissues during normal growth conditions and in response to stress
      leading to cellular dehydration (e.g. drought, low temperature and salinity).
      DHNs are localized in different cell compartments, such as the cytosol, nucleus,
      mitochondria, vacuole, and the vicinity of the plasma membrane; however, they are
      primarily localized to the cytoplasm and nucleus. The precise function of
      dehydrins has not been established yet, but in vitro experiments revealed that
      some DHNs (YSK(n)-type) bind to lipid vesicles that contain acidic phospholipids,
      and others (K(n)S) were shown to bind metals and have the ability to scavenge
      hydroxyl radicals [Asghar, R. et al. Protoplasma 177 (1994) 87-94], protect lipid
      membranes against peroxidation or display cryoprotective activity towards
      freezing-sensitive enzymes. The SK(n)-and K-type seem to be directly involved in
      cold acclimation processes. The main question arising from the in vitro findings
      is whether each DHN structural type could possess a specific function and tissue
      distribution. Much recent in vitro data clearly indicates that dehydrins
      belonging to different subclasses exhibit distinct functions.

PMID- 16983452
TI  - Building collaborative networks for HIV/AIDS vaccine development: the AVIP
      experience.
AB  - The need for an effective HIV/AIDS vaccine is imperative to halt a pandemic that
      involves more than 40 million individuals worldwide as of 2005 and is causing
      enormous socio-economic losses, especially in developing countries (DC). The
      overall failure of more than two decades of HIV vaccine research justifies the
      demands for a concerted effort for the rapid development of new and efficacious
      vaccines against HIV/AIDS. In this context, building international collaborative
      networks is a must for speeding up scientific research and optimizing the use of
      funding in a synergistic fashion, as resources for HIV/AIDS are limited and do
      not involve most of the biggest Pharmas that are more interested in drug
      discovery. The AIDS Vaccine Integrated Project (AVIP) consortium is an example of
      synergistic partnership of international European Union and DC experts with a
      common research goal. AVIP is a European Commission-funded (FP-6), consortium
      based, 5-year program directed to the fast development of new HIV/AIDS vaccine
      candidates to be tested in phase I clinical trials in Europe for future
      advancement to phase II/III testing in DC. To ensure their rapid development,
      AVIP novel combined vaccines include both regulatory and structural HIV antigens,
      which have already been tested, as single components, in phase I clinical trials.
      In particular, such combination vaccines may be superior to earlier vaccine
      candidates, the vast majority of which are based only on either structural or
      regulatory HIV products. In fact, the generation of immune responses to both
      types of viral antigens expressed either early (regulatory products) or late
      (structural products) during the viral life cycle can maximize immune targeting
      of both primary or chronic viral infection. Further, the rational design of
      combined vaccines allows exploitation of immunomodulatory functions of HIV
      regulatory proteins, which can improve immunity against structural vaccine
      components. The building of the AVIP consortium and its scientific strategy will
      be reviewed in this paper as an example of the establishment of a consortium
      regulated by a specific intellectual property agreement.

PMID- 16983454
TI  - Is a genetic defect in Fkbp6 a common cause of azoospermia in humans?
AB  - FK506-binding protein 6 (Fkbp6) is a member of a gene family containing a prolyl
      isomerase/FK506-binding domain and tetratricopeptide protein-protein interaction
      domains. Recently, the targeted inactivation of Fkbp6 in mice has been observed
      to result in aspermic males and the absence of normal pachytene spermatocytes.
      The loss of Fkbp6 results in abnormal pairing and a misalignment of the
      homologous chromosomes, and in non-homologous partner switches and autosynapsis
      of the X chromosome cores in meiotic spermatocytes. In this study, we analyzed
      whether human FKBP6 gene defects might be associated with human azoospermia. We
      performed a mutation analysis in all the coding regions of the human FKBP6 gene
      in 19 patients with azoospermia resulting from meiotic arrest. The expression of
      the human FKBP6 gene was specific to the testis, and a novel polymorphism site,
      245C --> G (Y60X) could be found in exon 3. Our findings suggest that the human
      FKBP6 gene might be imprinted in the testis based on an analysis using two
      polymorphism sites.

PMID- 16983455
TI  - A comparative gene-expression analysis of CD34+ hematopoietic stem and progenitor
      cells grown in static and stirred culture systems.
AB  - Static and stirred culture systems are widely used to expand hematopoietic cells,
      but differential culture performances are observed between these systems. We
      hypothesize that these differential culture outcomes are caused by the
      physiological responses of CD34(+) hematopoietic stem and progenitor cells
      (HSPCs) to the different physical microenvironments created in these culture
      devices. To understand the genetic changes provoked by culture microenvironments,
      the gene expression profiling of CD34(+) HSPCs grown in static and stirred
      culture systems was compared using SMART-PCR and cDNA arrays. The results
      revealed that 103 and 99 genes were significantly expressed in CD34(+) cells from
      static and stirred systems, respectively. Of those, 91 have similar levels of
      expression, while 12 show differential transcription levels. These differentially
      expressed genes are mainly involved in anti-oxidation, DNA repair, apoptosis, and
      chemotactic activity. A quantitative molecular understanding of the influences of
      growth microenvironments on transcriptional events in CD34(+) HSPCs should give
      new insights into optimizing culture strategies to produce hematopoietic cells.

PMID- 16983456
TI  - Comparative serial analysis of gene expression of transcript profiles of tomato
      roots infected with cyst nematode.
AB  - We analyzed global transcripts for tomato roots infected with the cyst nematode
      Globodera rostochiensis using serial analysis of gene expression (SAGE). SAGE
      libraries were made from nematode-infected roots and uninfected roots at 14 days
      after inoculation, and the clones including SAGE tags were sequenced. Genes were
      identified by matching the SAGE tags to tomato expressed sequence tags and cDNA
      databases. We then compiled a list of numerous genes according to the mRNA levels
      that were altered after cyst nematode infection. Our SAGE results showed
      significant changes in expression of many unreported genes involved in nematode
      infection. Of these, for discussion we selected five SAGE tags of RSI-1, BURP
      domain-containing protein, hexose transporter, P-rich protein, and PHAP2A that
      were activated by cyst nematode infection. Over 20% of the tags that were
      upregulated in the infected root have unknown functions (non-annotated),
      suggesting that we can obtain information on previously unreported and
      uncharacterized genes by SAGE. We can also obtain information on previously
      reported genes involved in nematode infection (e.g., multicystatin, peroxidase,
      catalase, pectin esterase, and S-adenosylmethionine transferase). To evaluate the
      validity of our SAGE results, seven genes were further analyzed by
      semiquantitative reverse transcriptase-polymerase chain reaction and Northern
      blot hybridization; the results agreed well with the SAGE data.

PMID- 16983457
TI  - The importance of communication in secondary fragility fracture treatment and
      prevention.
AB  - INTRODUCTION: We report on a Canadian longitudinal qualitative case study of
      midlife women with fragility fractures, their treating orthopaedic surgeons and
      family physicians. METHODS: Women and their treating physicians were followed for
      an average of one year post fracture to investigate the health outcomes and what,
      if any, follow-up occurred aimed at secondary fracture prevention. The final
      dataset includes 223 interviews gathered from women aged 40 to 65 with fragility
      fractures, orthopaedic surgeons and family physicians. RESULTS: The circle of
      care for those with fragility fractures is disrupted at vital communication
      junctures: (1) the inconsistent flow of information between acute care
      institutions and family physicians; (2) unidirectional and inconsistent
      communication from orthopaedic surgeons to family physicians; and (3) competing
      demands of the cast clinic environment and patient expectations. It is not the
      lack of will that is undermining the consistent and detailed communication among
      patients, physicians and institutions. It is the episodic nature of fracture care
      that makes communication among involved parties difficult, if not impossible.
      CONCLUSIONS: Communication about events, acuity and clear expectations around
      roles and follow-up is urgently needed to improve communication throughout the
      circle of care to support secondary fracture prevention. Fractures from a
      standing height or similar trauma in women aged 40 to 65 should be treated as
      suspicious fractures and followed-up to investigate the underlying bone
      condition. This article reports on challenges and barriers to clear communication
      among women, their orthopaedic surgeons and family physicians that is necessary
      for follow-up and prevention of future fractures.

PMID- 16983458
TI  - Vertebral height restoration in osteoporotic compression fractures: kyphoplasty
      balloon tamp is superior to postural correction alone.
AB  - INTRODUCTION: Kyphoplasty has been shown to restore vertebral height and sagittal
      alignment. Proponents of vertebroplasty have recently demonstrated that many
      vertebral compression fractures (VCFs) are mobile and positional correction can
      lead to clinically significant height restoration. The current investigation
      tested the hypothesis that positional maneuvers do not achieve the same degree of
      vertebral height correction as kyphoplasty balloon tamps for the reduction of low
      energy VCFs. METHODS: Twenty-five consecutive patients with a total of 43
      osteoporotic VCFs were entered into a prospective analysis. Each patient was
      sequentially evaluated for postural and balloon vertebral fracture reduction.
      Preoperative standing and lateral radiographs of the fractured vertebrae were
      compared with prone cross-table lateral radiographs with the patient in a hyper
      extension position and on pelvic and sternal rolls. Following positional
      manipulation, patients underwent a unilateral balloon kyphoplasty. Postoperative
      standing radiographs were evaluated for the percentage of height restoration
      related to positioning and balloon kyphoplasty. RESULTS: In the middle portion of
      the vertebrae, the percentage available for restoration restored with extension
      positioning was 10.4% (median 11.1%) and after balloon kyphoplasty was 57.0%
      (median 62.2%). This difference was statistically significant (p<0.001). Thus,
      kyphoplasty provided an additional 46.6% of the height available for restoration
      from the positioning alone. With operative positioning, 51.2% of VCFs had >10%
      restoration of the central portion of the vertebral body, whereas 90.7% of
      fractures improved at least 10% following balloon kyphoplasty (p<0.002).
      CONCLUSION: Although this study supports the concept that many VCFs can be moved
      with positioning, balloon kyphoplasty enhanced the height reduction >4.5-fold
      over the positioning maneuver alone and accounted for over 80% of the ultimate
      reduction. If height restoration is the goal, kyphoplasty is clearly superior in
      most cases to the positioning maneuver alone.

PMID- 16983459
TI  - An estimate of the worldwide prevalence and disability associated with
      osteoporotic fractures.
AB  - OBJECTIVE: The aim of this study was to quantify the global burden of
      osteoporotic fracture worldwide. METHODS: The incidence of hip fractures was
      identified by systematic review and the incidence of osteoporotic fractures was
      imputed from the incidence of hip fractures in different regions of the world.
      Excess mortality and disability weights used age- and sex-specific data from
      Sweden to calculate the Disability Adjusted Life Years (DALYs) lost due to
      osteoporotic fracture. RESULTS: In the year 2000 there were an estimated 9.0
      million osteoporotic fractures of which 1.6 million were at the hip, 1.7 million
      at the forearm and 1.4 million were clinical vertebral fractures. The greatest
      number of osteoporotic fractures occurred in Europe (34.8%). The total DALYs lost
      was 5.8 million of which 51% were accounted for by fractures that occurred in
      Europe and the Americas. World-wide, osteoporotic fractures accounted for 0.83%
      of the global burden of non-communicable disease and was 1.75% of the global
      burden in Europe. In Europe, osteoporotic fractures accounted for more DALYs lost
      than common cancers with the exception of lung cancer. For chronic musculo
      skeletal disorders the DALYs lost in Europe due to osteoporosis (2.0 million)
      were less than for osteoarthrosis (3.1 million) but greater than for rheumatoid
      arthritis (1.0 million). CONCLUSION: We conclude that osteoporotic fractures are
      a significant cause of morbidity and mortality, particularly in the developed
      countries.

PMID- 16983460
TI  - Role of the simultaneous sequential strategy for failed acute sinus restoration
      after modified left maze procedure for persistent atrial fibrillation with
      concomitant mitral surgery.
AB  - BACKGROUND: We assessed whether the simultaneous sequential strategy could (1)
      achieve additional sinus restoration for those patients who were not in sinus
      rhythm while coming off bypass after modified left maze procedure and (2) attain
      the same long-term success rates as the bi-atrial maze procedure in patients with
      persistent atrial fibrillation (AF) and mitral valve disease. MATERIALS AND
      METHODS: Twenty-seven consecutive patients - ten men and 17 women with a mean age
      of 52 +/- 13 years, all with persistent AF and mitral valve disease - underwent
      the modified maze procedure with the simultaneous sequential strategy. In the
      first phase, the modified left atrial maze operation was carried out with
      concomitant valvular surgery; the right side maze operation was subsequently
      carried out as a second phase of the sequential strategy only if AF re-appeared
      following the spontaneous restoration of heart beats during the operation.
      RESULTS: Twenty patients (74.1%) underwent the left atrial maze procedure only,
      and seven patients (25.9%) required the subsequent right atrial maze procedure as
      part of the sequential strategy. At a mean follow-up of 15.1 +/- 7.7 months, six
      of the 27 patients (22.2%) who underwent additional right atrial maze procedure
      had restored sinus rhythm. At a mean follow-up of 17.8 +/- 7.3 months, 24 of the
      27 patients (88.9%) had restored sinus rhythm and 22 patients (81.5%) had
      restored bi-atrial transport function (right atrial filling fraction: 40.8 +/-
      11.7%; left atrial filling fraction: 22.9 +/- 8.1%) after application of the
      sequential strategy. CONCLUSIONS: Compared with modified left atrial maze
      procedure, the application of the simultaneous sequential strategy successfully
      restored sinus rhythm in an additional 22.2% of patients with persistent AF. The
      overall sinus conversion rate of 88.9% was comparable with that of the standard
      bi-atrial maze procedure.

PMID- 16983461
TI  - Effect of prevailing local treatment options of breast cancer on survival outside
      controlled clinical trials: experience of a specialist breast unit in North
      India.
AB  - BACKGROUND: This study aimed at analyzing different treatments of breast cancer
      (BC) prevalent in the region, their effect on patients' survival, and discusses
      the most suitable method within available resources. METHODS: The study was set
      up at a tertiary care hospital in north India. We retrospectively reviewed data
      of 473 female BC patients who attended the departments of Surgical Oncology and
      Radiotherapy from January 1997 to December 1999. Patients with cTNM stage IV and
      inoperable stage III were included; those who defaulted or were lost to follow-up
      were excluded. Out of 473 patients, 372 were selected. The selected patients were
      divided into groups on the basis of place and type of local treatment they
      received: (1) local excision only, (2) standard breast conservation therapy
      (BCT), (3) total mastectomy (TM) + axillary lymph node dissection + radiotherapy
      (RT), and (4) modified radical mastectomy (MRM) + RT. Data regarding recurrence
      and survival were analyzed in December 2005. Minimum follow-up was 6 years.
      RESULTS: Overall recurrence rates were significantly higher in patients operated
      elsewhere (P <0.0001). Of 194 operated at our Breast Unit, 25 (14.6%) of 171 MRM
      patients and none of 23 BCT had recurrence. Of 178 patients operated elsewhere,
      44 (100%), 6 (42.9%), 41 (41%), and 8 (40%) developed recurrence in groups 1, 2,
      3, and 4 respectively. Overall survival was significantly better in patients with
      MRM at our unit versus TM outside (93.6% vs. 80%). CONCLUSIONS: Several types of
      treatment from improper local excision alone, BCT, TM, to a carefully done MRM
      are prevalent here. Properly done, MRM yields significant local control with
      survival benefit and appears to remain the gold standard in management of our BC
      patients.

PMID- 16983467
TI  - Treatment of abdominal compartment syndrome with subcutaneous anterior abdominal
      fasciotomy in severe acute pancreatitis.
AB  - BACKGROUND: Managing the abdominal compartment syndrome associated with severe
      acute pancreatitis by the open abdomen method is associated with considerable
      morbidity and resource utilization. METHODS: A technique of subcutaneous anterior
      abdominal fasciotomy is described for the first time in two patients with severe
      acute pancreatitis. RESULTS: Following the procedure, the intra-abdominal
      pressure decreased from 30 mmHg immediately to 23 mmHg and to a sustained level
      of 12-14 mmHg in the first patient, and from 35 mmHg immediately to 23 mmHg and
      to a sustained level of 14-19 mmHg in the second patient. CONCLUSIONS: The
      subcutaneous anterior abdominal fasciotomy is a promising method for safe and
      effective abdominal decompression with sustained effect and avoiding the
      morbidity associated with the alternative open abdomen techniques.

PMID- 16983469
TI  - Clinical significance of lymph node metastasis of thyroid papillary carcinoma
      located in one lobe.
AB  - BACKGROUND: Previous studies have shown that lymph node metastasis can be of
      prognostic value. In this study, we investigated the clinical significance of
      node metastasis focusing on metastasis in the central compartment for patients
      with papillary carcinoma located in one lobe. PATIENTS AND METHODS: We
      investigated the frequency of lymph node metastasis in 759 patients with
      papillary carcinoma to determine whether and how such metastasis affects disease
      free survival (DFS). RESULTS: Central node metastasis was observed in 63% of
      patients, and the frequency was increased in relation to tumor size. The
      frequency of lateral node metastasis was 62.0%, which was also directly related
      to tumor size. On multivariate analysis of cases showing tumor larger than 1 cm,
      central node metastasis was recognized as an independent prognostic factor of
      DFS. The frequency of metastasis to the paratracheal nodes contralateral to the
      tumor was drastically elevated for tumors larger than 1 cm, but metastasis to
      this region did not independently predict worse DFS. CONCLUSION: Central node
      metastasis independently predicts a worse DFS for patients with papillary
      carcinoma larger than 1 cm.

PMID- 16983470
TI  - Hepatectomy for colorectal liver metastases with macroscopic intrabiliary tumor
      growth.
AB  - OBJECTIVES: We set out to clarify the clinicopathologic characteristics of
      colorectal liver metastases with macroscopic intrabiliary tumor growth and to
      determine optimal surgical management. METHODS: Over 15 years, 6 of 103 patients
      undergoing hepatectomy for colorectal liver metastases had macroscopic
      intrabiliary tumor growth and were analyzed retrospectively. RESULTS: We
      performed 11 operations for the 6 patients, consisting of 10 hepatectomies
      (including 1 hepatopancreatoduodenectomy) and 1 pancreatoduodenectomy. Three
      patients survived more than 5 years: 1 died of pulmonary emphysema with no sign
      of recurrence 101 months after initial hepatectomy; the 2 others were alive with
      no sign of recurrence at 74 and 145 months after initial hepatectomy. Median
      survival time of all 6 patients was 87.5 months. Histologically, intrabiliary
      tumor growth had two components: intraluminal and intraepithelial extension. In
      the proximal direction, distance between these two components ranged from 4-10
      mm. CONCLUSION: Aggressive surgical treatment can improve chances of long-term
      survival for patients with macroscopic intrabiliary growth of colorectal liver
      metastasis. Although nonanatomic limited resection is a common procedure for
      colorectal liver metastasis, anatomic hepatobiliary resection is recommended.

PMID- 16983471
TI  - Who will care for Iraq's wounded warriors? Health policy and national security.
AB  - INTRODUCTION: Since 2003, Iraq has struggled to build a single national health
      system administered by the Iraqi Ministry of Health, but politics, lack of
      leadership, and a cultural bias against treating soldiers in civilian hospitals
      have hindered access to care for members of Iraq's armed forces who are wounded
      in combat. METHODS: U.S. surgeons are providing trauma care for Iraqi soldiers in
      American field hospitals, with more than 80% of hospital bed days occupied by
      Iraqis. At the same time, Iraqi hospitals have been treating the many civilian
      casualties of violence, and the Ministry of Health has greatly improved its
      emergency response and management capabilities over the past year. RESULTS:
      Ministry of Health hospitals have adequate surgical capabilities and bed capacity
      to care for both civilian and security forces casualties. Faltering attempts to
      develop a national health policy that provides comprehensive care for Iraqi
      Security Forces will jeopardize Iraq's ability to assume responsibilities for the
      country's national defense, and could delay the withdrawal of Coalition military
      forces from Iraq. CONCLUSIONS: It is imperative that leadership of the new
      government of Iraq and the international surgical community strongly endorse the
      implementation of a single health care system for all Iraqis.

PMID- 16983472
TI  - Commercial mesh versus Nylon mosquito net for hernia repair. A randomized double
      blind study in Burkina Faso.
AB  - PURPOSE: The goal of this study was to investigate whether locally available
      Nylon mosquito net might be a useful alternative to expensive commercial mesh
      implants for hernia repair, a clinical randomized double-blind study was
      performed. MATERIALS AND METHODS: Over a period of 3 months 35 patients with a
      total of 40 inguinal hernias were randomized for hernia repair with either a
      commercial graft (Ultrapro) or a piece of sterilized 100% Nylon mesh available as
      mosquito net in most African village markets. The surgeons' comfort in handling
      the meshes, the incidence of complications, and the patients' quality of life
      before and 30 days after hernia repair were evaluated. In addition, the costs of
      the two materials were compared. RESULTS: There was no significant difference in
      the clinical short-term outcome of the hernia treatment or the surgeons' comfort
      in handling the two different materials. The price of the locally bought Nylon
      mesh was 0.0043 US dollars as compared to 108 US dollars for the commercial mesh.
      CONCLUSIONS: In situations where superior results of hernia repair depend on the
      use of a mesh prosthesis but where commercial material is not available or
      affordable, the use of Nylon mosquito net may be an alternative. Further studies
      with a larger number of patients and longer follow-up are justified and
      recommended.

PMID- 16983473
TI  - Management of right colon diverticulitis: a 10-year experience.
AB  - BACKGROUND: Controversies abound as regards the optimal treatment for patients
      with diverticulitis of the right colon. METHODS: This is a retrospective review
      of 113 patients with a diagnosis of right colonic diverticulitis who received
      treatment at the China Medical University Hospital from July 1994 to June 2004.
      RESULTS: Medical therapy was undertaken in 56 patients diagnosed preoperatively
      with uncomplicated diverticulitis. All but one patient was successfully treated
      with bowel rest and antibiotics. Of the 51 patients with a preoperative diagnosis
      of acute appendicitis, 32 received appendectomy along with postoperative
      antibiotic therapy, 8 received diverticulectomy in addition to appendectomy, and
      11 received colectomy. In all, 17 patients required right hemicolectomy or
      ileocecal resection due to diverticulitis-related complications or suspected
      malignancy. Of the 87 (56-1+32) patients who responded to conservative treatment,
      11 developed recurrent diverticulitis. All 11 patients were successfully treated
      with medical therapy, and 2 subsequently received elective right hemicolectomy.
      Of the 9 patients who received medical treatment alone at the second attack, 2
      suffered a third attack. Both were successfully managed with medical therapy.
      CONCLUSIONS: For uncomplicated diverticulitis of the right colon diagnosed
      preoperatively, antibiotic therapy with bowel rest is an effective treatment.
      Once it is encountered during surgery for presumed acute appendicitis, a
      conservative approach involving prophylactic appendectomy and postoperative
      antibiotics is recommended. For patients with recurrent diseases, medical
      treatment is still safe and efficient. Colectomy is indicated when complications
      occur or when malignancy is strongly suspected.

PMID- 16983474
TI  - Indirect inguinal herina: towards less invasive surgery in rural conditions.

PMID- 16983475
TI  - Prophylactic antibiotics in chest trauma: a meta-analysis of high-quality
      studies.
AB  - BACKGROUND: Use of antibiotics in patients with isolated chest trauma is
      controversial. Available studies offer contradictory results because of small
      sample sizes. However, information provided by recent randomized controlled
      trials (RCT) included in a systematic review and meta-analysis could help solve
      the controversy. We performed a systematic review using high-quality information
      related to the use of antibiotics in patients with a chest tube. METHODS: We
      developed a systematic review to evaluate the effectiveness of prophylactic
      antibiotics in chest-trauma patients. Studies included were class I RCT comparing
      prophylactic antibiotics versus placebo in patients with isolated chest trauma.
      Main outcomes were posttraumatic empyema and pneumonia. RESULTS: Five Class I
      studies were selected. There were statistically significant differences regarding
      the frequency of posttraumatic empyema (RR 0.19) and pneumonia (RR 0.44) in favor
      of the use of prophylactic antibiotics when compared with placebo. CONCLUSIONS:
      The use of prophylactic antibiotics in patients with chest trauma decreases the
      incidence of posttraumatic empyema and pneumonia.

PMID- 16983476
TI  - Benefits of a synbiotic formula (Synbiotic 2000Forte) in critically Ill trauma
      patients: early results of a randomized controlled trial.
AB  - BACKGROUND: Since probiotics are considered to exert beneficial health effects by
      enhancing the host's immune response, we investigated the benefits of a
      synbiotics treatment on the rate of infections, systemic inflammatory response
      syndrome (SIRS), severe sepsis, and mortality in critically ill, mechanically
      ventilated, multiple trauma patients. Length of stay in the intensive care unit
      (ICU) and number of days under mechanical ventilation were also evaluated.
      METHOD: Sixty-five patients were randomized to receive once daily for 15 days a
      synbiotic formula (Synbiotic 2000Forte, Medipharm, Sweden) or maltodextrin as
      placebo. The synbiotic preparation consisted of a combination of four probiotics
      (10(11) CFU each): Pediococcus pentosaceus 5-33:3, Leuconostoc mesenteroides 32
      77:1, L. paracasei ssp. paracasei 19; and L. plantarum 2,362; and inulin, oat
      bran, pectin, and resistant starch as prebiotics. Infections, septic
      complications, mortality, days under ventilatory support, and days of stay in ICU
      were recorded. RESULTS: Synbiotic-treated patients exhibited a significantly
      reduced rate of infections (P = 0.01), SIRS, severe sepsis (P = 0.02), and
      mortality. Days of stay in the ICU (P = 0.01) and days under mechanical
      ventilation were also significantly reduced in relation to placebo (P = 0.001).
      CONCLUSION: The administration of this synbiotic formula in critically ill,
      mechanically ventilated, multiple trauma patients seems to exert beneficial
      effects in respect to infection and sepsis rates and to improve the patient's
      response, thus reducing the duration of ventilatory support and intensive care
      treatment.

PMID- 16983477
TI  - Quality of life following laparoscopic anterior 90 degrees versus Nissen
      fundoplication: results from a multicenter randomized trial.
AB  - BACKGROUND: The short-term clinical outcomes from a multicenter prospective
      randomized trial of laparoscopic Nissen versus anterior 90 degrees partial
      fundoplication have been reported previously. These demonstrated a high level of
      satisfaction with the overall outcome following anterior 90 degrees
      fundoplication. However, the results of postoperative objective tests and
      specific clinical symptoms are not always consistent with an individual patient's
      functional status and general well being following surgery, and quality of life
      (QOL) is also an important outcome to consider following surgery for reflux.
      Hence, QOL information was collected in this trial to investigate the hypothesis:
      improvements in QOL following laparoscopic antireflux surgery are greater after
      anterior 90 degrees partial fundoplication than after Nissen fundoplication.
      METHODS: Patients undergoing a laparoscopic fundoplication for gastro-esophageal
      reflux at one of nine university teaching hospitals in six major cities in
      Australia and New Zealand were randomized to undergo either laparoscopic Nissen
      or anterior 90 degrees partial fundoplication. Quality of life before and after
      surgery was assessed using validated questionnaires - the Short Form 36 general
      health questionnaire (SF36) and an Illness Behavior Questionnaire (IBQ). Patients
      were asked to complete these questionnaires preoperatively and at 3, 6, 12 and 24
      months postoperatively. RESULTS: One hundred and twelve patients were randomized
      to undergo a Nissen fundoplication (52) or a 90 degrees anterior fundoplication
      (60). Patients who underwent anterior fundoplication reported significant
      improvements in eight of the nine SF36 scales compared to four of the nine
      following a Nissen fundoplication. The majority of these improvements occurred
      early in the postoperative period. With respect to the illness behavior data,
      there were no significant differences between the two procedures. Both groups had
      a significant improvement in disease conviction scores at all time points
      compared to their preoperative scores. CONCLUSIONS: Patients undergoing
      laparoscopic anterior 90 degrees partial fundoplication reported more QOL
      improvements in the early postoperative period than patients undergoing a Nissen
      fundoplication. However, the QOL outcome for both procedures was similar at later
      follow-up.

PMID- 16983478
TI  - Assessment of nutritional status and prediction of postoperative liver function
      from serum apolioprotein A-1 levels with hepatectomy.
AB  - BACKGROUND: We investigated the usefulness of apolipoprotein A-1 (apoA) as an
      indicator of nutritional status, and the correlation of the preoperative apoA
      level with changes in postoperative liver function following hepatectomy.
      METHODS: One hundred patients underwent hepatectomy. Serum levels of apoA,
      prealbumin (prealb), retinol-binding protein (RBP), lectin-cholesterol
      acyltransferase (LCAT), hyarulonate (HA), indocyanine green dye retention at 15
      minutes (ICG), and the receptor index of Tc-GSA scintigraphy (LHL15) were
      measured at preoperation and on postoperative days (POD) 7 and 14. Partial
      resection was carried out in 62 cases, segmentectomy in nine cases, and
      bisegmentectomy in 29 cases. Co-existent liver conditions were normal liver (NL)
      in 43 cases, chronic hepatitis (CH) in 29 cases, and liver cirrhosis (LC) in 28
      cases. RESULTS: In most cases the serum apoA level had decreased on POD 7, and
      recovered on POD 14. There were no significant differences in the changes of apoA
      between the individual operative procedures. Although preoperative apoA had
      almost the same value in the NL, CH, and LC cases, apoA in LC cases on POD 14 was
      the lowest of all cases. The apoA level showed significant correlations with
      prealb, LCAT, and HA on POD 14. All cases were divided into two groups (group N:
      apoA over 91 mg/dl; group L: apoA under 90 mg/dl) based on the preoperative serum
      apoA level. On POD 14, the ICG, LHL15, and HA of group L were significantly
      deteriorated compared with those of group L. CONCLUSION: The serum level of apoA
      reflects the changes in hepatic protein synthetic ability after hepatectomy;
      therefore, it may be possible to estimate recovery of nutritional status after
      hepatectomy from serum apoA. Moreover, we can predict postoperative deterioration
      of liver function from the preoperative apoA level.

PMID- 16983479
TI  - Distinct recurrence pattern and outcome of adenocarcinoma of the gastric cardia
      in comparison with carcinoma of other regions of the stomach.
AB  - BACKGROUND: Carcinoma arising in the cardioesophageal junction is a distinct
      clinical entity compared with tumors located in other regions of the stomach. The
      prognosis for adenocarcinoma of the upper stomach is considered to be relatively
      poorer than carcinomas of the more distal stomach. We have therefore investigated
      patients with carcinoma of the gastric cardia in order to evaluate the underlying
      cause of this poor prognosis. MATERIALS AND METHODS: Clinicopathologic features
      and postoperative prognosis of 101 patients with carcinoma of the cardia were
      evaluated and compared with findings on 1884 patients with tumors in other
      regions of the stomach. RESULTS: Tumors of the cardia had a mean size of 6.8 cm,
      which was significantly larger than the mean size of 5.9 cm for tumors found in
      the middle- and lower third of the stomach. The incidence of serosal invasion,
      lymph node metastasis, and lymphatic and blood vessel invasion was higher in
      association with adenocarcinoma of the cardia than with adenocarcinoma in
      remaining parts of the stomach. In the analysis of patients who had undergone
      curative resection, the 5-year survival rates were 61.6, 79.1, and 82.6% in
      patients with carcinoma of the cardia, upper one-third, and remaining middle- and
      lower one-third of the stomach, respectively, and the differences were
      statistically significant. Multivariate analysis indicated that adenocarcinoma of
      the gastric cardia is an independent prognostic factor. With regard to the site
      of recurrence, both lymph node and hematogenous recurrence were observed more
      frequently in the cardia than in the remaining parts of the stomach. CONCLUSIONS:
      Our data indicate that the prognosis of patients with adenocarcinoma of the
      gastric cardia is extremely poor. To improve their prognosis, new treatments in
      addition to gastrectomy with extensive lymph node dissection are needed.

PMID- 16983480
TI  - Observational assessment of surgical teamwork: a feasibility study.
AB  - BACKGROUND: Teamwork is fundamental to effective surgery, yet there are currently
      no measures of teamwork to guide training, evaluate team interventions or assess
      the impact of teamwork on outcomes. We report the first steps in the development
      of an observational assessment of teamwork and preliminary findings. METHOD: We
      observed 50 operations in general surgery from a single operating theater using a
      measure of teamwork specifically developed for use in the operating theater. The
      OTAS (Observational Teamwork Assessment for Surgery) comprises a procedural task
      checklist centered on the patient, equipment and communications tasks and ratings
      on team behavior constructs, namely: communication, co-operation, co-ordination,
      shared-leadership and monitoring. RESULTS: Ratings of overall team performance
      were reasonably high, though variable, but there was evidence that clinically
      significant steps were being missed which at the very least eroded safety
      margins. There was, for instance, a frequent failure to check both surgical and
      anesthetic equipment and a failure to confirm the procedure verbally, patient
      notes were missing in about one-eighth of the cases and delays or changes
      occurred in over two-thirds of the cases. CONCLUSIONS: This study takes an
      initial step towards developing measures of team performance in surgery that are
      defined in relation to tasks and behaviors of the team. The observational method
      of assessment is feasible and can provide a wealth of potentially valuable
      research data. However, for these measures to be used for formal assessment, more
      research is needed to make them robust and standardized.

PMID- 16983481
TI  - Adrenal cysts: an institutional experience.
AB  - INTRODUCTION: Adrenal cysts are rare clinical entities. We report our
      institutional experience with adrenal cysts and also assess various management
      options. MATERIAL AND METHODS: Over the past 15 years the Department of Endocrine
      Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow,
      India, has had seven cases of adrenal cysts, of which two were functional: one
      patient had Cushing's syndrome and the other patient had pheochromocytoma. The
      other five cases were incidentally detected. Ultrasound scan and computerized
      tomography (CT) scan were the imaging modalities. Four patients had a single
      cyst, two patients had two cysts, and one patient had multiple unilateral cysts.
      RESULTS: None of these cysts had foci of malignancy. Laparoscopic adrenalectomy
      was possible in three patients with no morbidity or mortality. DISCUSSION: The
      reported incidence in clinical series has been 5.4%. Pseudocysts, endothelial
      cysts, epithelial cysts, and hemorrhagic cysts have been commonly described. The
      management can be conservative or surgical. It is generally agreed that a
      hormonal work-up is necessary in all cases of adrenal cysts to rule out a sub
      clinical disease. Adrenal neoplasms, including adrenocortical carcinomas, can be
      associated with cysts that are benign in appearance. Percutaneous aspiration has
      been suggested as an alternative treatment option if the cyst is not hormonally
      active and if there is no suspicion of malignancy. However, surgical excision
      provides a definite histopathological diagnosis and also removes the fear of
      future complications such as hemorrhage into the cyst and local pressure effects
      due to the tumor. CONCLUSIONS: Given that the adrenals are a vascular gland and
      taking into consideration the possibilities of bleeding and complications in the
      cyst, our treatment of choice is the elective excision of adrenal cysts.

PMID- 16983482
TI  - Malpractice, standards and surgical journals.

PMID- 16983483
TI  - Receptor-receptor interactions as studied with microdialysis. Focus on NTR/D2
      interactions in the basal ganglia.
AB  - Using mono and dualprobe(s) microdialysis in the basal ganglia of the freely
      moving rat evidence has been obtained that neurotensin (NT) in threshold
      concentrations can counteract the D(2) agonist (intrastriatally perfused) induced
      inhibition of striatal dopamine (DA) release and of pallidal GABA release from
      the striato-pallidal GABA pathway, effects that are blocked by a NTR(1)
      antagonist SR48692. These results indicate the existence of antagonistic
      intramembrane NTR/D(2) receptor interactions in the striatal DA terminals and in
      the somato-dendritic regions of the striato-pallidal GABA neurons. By the NT
      induced reduction of the D(2) mediated signals at the striatal pre- and
      postjunctional level DA transmission is switched towards a D(1) mediated
      transmission leading to increased activity in the striatopallidal and
      striatonigral GABA pathways. The former action will contribute to the motor
      inhibition and catalepsy found with NT treatment and underlies the use of NT
      receptor antagonists as a treatment strategy for Parkinson's disease. Nigral NT
      by an antagonistic NTR/D(2) receptor interaction in the DA cell body and
      dendrites may also increase nigral DA release leading to a D(2) mediated
      inhibition of the nigrothalamic GABA pathway. Such an effect, will instead result
      in antiparkinsonian actions. Thus, increases in NT transmission will have
      different consequences for the motor system depending upon where in the basal
      ganglia the increase takes place.

PMID- 16983484
TI  - Calmodulin concentrates at the apex of growing hyphae and localizes to the
      Spitzenkorper in Aspergillus nidulans.
AB  - The calmodulin (CaM) localization pattern in the growing hyphal tip of
      Aspergillus nidulans was studied with the functional GFP::CaM fusion protein. A
      faint tip-high gradient of CaM was found in the growing hyphal tip, with CaM
      highly localized in the region corresponding to the Spitzenkorper forming a
      bright granule. The position of highly concentrated CaM in the extreme apex
      seemed to determine the orientation of the hypha. The normal pattern of CaM
      localization was also shown to be dependent on the integrated actin cytoskeleton.
      When the growth of the hyphal tip ceased, CaM failed to localize in the bright
      granule and was evenly distributed in the hyphal tip. These findings suggest that
      CaM may play an important role in establishing and maintaining apical
      organization, morphogenesis, and growth in Aspergillus nidulans.

PMID- 16983485
TI  - Involvement of gibberellin in tracheary element differentiation and lignification
      in Zinnia elegans xylogenic culture.
AB  - Gibberellin (GA) is considered an important growth regulator involved in many
      aspects of plant development. However, little is known about the relationship
      between GA and lignification. In this study, we analyzed the role of GA in
      tracheary element (TE) differentiation and lignification using a Zinnia elegans
      xylogenic culture. When gibberellic acid-3 (GA3) was exogenously supplied, a
      slight increase in the frequency of TE differentiation and a remarkable increase
      in lignin content were observed. Computer image analysis of individual TEs showed
      that the lignification level of each TE was significantly increased in the
      culture treated with GA3 compared with those of the control. In contrast,
      suppression of TE differentiation and lignification was observed when GA
      biosynthesis was inhibited by ancymidol, paclobutrazol, or uniconazole. This
      suppression was restored by the addition of GA3. These results suggest that GA
      plays an important role in TE differentiation, and even more so in lignification.
      When conditioned medium obtained after 120 h of control culture was analyzed by
      high-performance liquid chromatography, many lignin precursors were detected.
      However, these lignin precursors were greatly reduced in the GA-treated culture.
      This result suggests that GA promotes lignification by activating the
      polymerization of lignin precursors.

PMID- 16983486
TI  - Mucor rouxii ultrastructure: cyclic AMP and actin cytoskeleton.
AB  - A comparative analysis of the effect of two compounds, dibutyryl-cyclic-AMP
      (dbcAMP) and latrunculin B, on the morphology and ultrastructure of the dimorphic
      fungus Mucor rouxii under aerobic growth conditions is presented. dbcAMP acts
      through the sustained activation of protein kinase A, and latrunculin B through
      the disruption of the actin cytoskeleton. Upon addition of these compounds to the
      growth medium at any stage of the germination process, cells lost polarised
      growth and switched to isodiametric growth. The effect was reversible. The
      morphologies, visualised by light microscopy or scanning electron microscopy
      (SEM), were alike. A switch from a rough to a smooth surface was observed by SEM
      when cells were repolarised by removal of the added compound. Ultrastructural
      changes under both conditions, as observed by transmission electron microscopy,
      were similar, the main feature being the enlargement of the cell wall, with
      irregular depositions, and detachment from the cell membrane. dbcAMP-treated
      cells showed a decrease in the number of glycogen granules compared with control
      and latrunculin B-treated cells. F-actin staining with fluorescein isothiocyanate
      phalloidin showed that both dbcAMP- and latrunculin B-treated cells displayed a
      much lower fluorescence than control cells, with only a few pale plaques. The
      results suggest that the sustained activation of protein kinase A, which impairs
      polarised growth, might exert its effect through a modification of actin
      cytoskeleton organisation, very probably also involving an integrinlike pathway,
      as judged by the cell wall detachment and loss of cell adhesiveness of the dbcAMP
      treated isodiametric cells.

PMID- 16983487
TI  - Calcium carbonate deposition in a cell wall sac formed in mulberry idioblasts.
AB  - Although calcium carbonate is known to be a common biomineral in plants, very
      little attention has been given to the biological control of calcium carbonate
      deposition. In mulberry leaves, a subcellular structure is involved in mineral
      deposition and is described here by a variety of cytological techniques. Calcium
      carbonate was deposited in large, rounded idioblast cells located in the upper
      epidermal layer of mulberry leaves. Next to the outmost region ("cap") of young
      idioblasts, we found that the inner cell wall layer expanded to form a peculiar
      outgrowth, named cell wall sac in this report. This sac grew and eventually
      occupied the entire apoplastic space of the idioblast. Inside the mature cell
      wall sac, various cellulosic membranes developed and became the major site of Ca
      carbonate deposition. Concentrated Ca2+ was pooled in the peripheral zone, where
      small Ca carbonate globules were present in large numbers. Large globules were
      tightly packed among multiple membranes in the central zone, especially in
      compartments formed by cellulosic membranes and in their neighboring membranes.
      The maximum Ca sink capacity of a single cell wall sac was quantified using
      enzymatically isolated idioblasts as approximately 48 ng. The newly formed
      outgrowth in idioblasts is not a pure calcareous body but a complex cell wall
      structure filled with substantial amounts of Ca carbonate crystals.

PMID- 16983488
TI  - Phylogenetics of Chinese Dryopteris (Dryopteridaceae) based on the chloroplast
      rps4-trnS sequence data.
AB  - Dryopteris is one of the largest and most taxonomically complex fern genera in
      the Dryopteridaceae, with 127 species occurring throughout temperate, sub
      temperate, subtropical, and tropical China. Investigations of the evolutionary
      relationships of a subset of these Chinese Dryopteris species, using DNA sequence
      based methods, specifically tested the monophyly of the genus and the validity of
      the previous subgeneric classifications. Sixty species of Dryopteris, four
      closely related non-Dryopteris and three species of Arachniodes, were used as
      outgroup taxa. The rps4-trnS region of the chloroplast genome was sequenced in
      these species for the first time. Both maximum parsimony (MP) and neighbor
      joining (NJ) analyses identified six polyphyletic clades that contained
      Dryopteris species. These results were supported by a Bayesian analysis of the
      same data set. The phylogenetic patterns strongly suggest the polyphyletic status
      of Dryopteris; the monophyletic groupings of the species do not correspond with
      either Fraser-Jenkins [In: Bull Brit Mus (Nat Hist) Bot 14(3):183-218, 1986} or
      Wu (In: Flora Reipublica Popularis Sinicae Tomus 5 (1) pp 1-241, 2000] subgeneric
      classification of Dryopteris, except in a few specific cases. This work
      represents the first molecular systematic analyses of Chinese Dryopteris, and we
      propose the next steps necessary to recognize new subgenera of the genus.

PMID- 16983490
TI  - Lipoxygenase inhibition: the neglected frontier for regulating chronic
      inflammation and pain.

PMID- 16983489
TI  - Obsessive-compulsive disorder and personality disorder: evidence from the British
      National Survey of Psychiatric Morbidity 2000.
AB  - BACKGROUND: Previous studies indicate that most individuals with obsessive
      compulsive disorder (OCD) have comorbid personality disorders (PDs), particularly
      from the anxious cluster. However, the nature and strength of this association
      remains unclear, as the majority of previous studies have relied heavily on
      clinical populations. We analysed the prevalence of screen positive personality
      disorder in a representative sample of adults with OCD living in private
      households in the UK. METHODS: A secondary analysis of data from the 2000 British
      National Survey of Psychiatric Morbidity. The prevalence of PD, as determined by
      the SCID-II questionnaire, was compared in participants with OCD, with other
      neuroses and non-neurotic controls. Within the OCD group we also analysed
      possible differences relating to sex and subtypes of the disorder. RESULTS: The
      prevalence of any screen positive PD in the OCD group (N=108) was 74%,
      significantly greater than in both control groups. The most common screen
      positive categories were paranoid, obsessive-compulsive, avoidant, schizoid and
      schizotypal. Compared to participants with other neuroses, OCD cases were more
      likely to screen positively for paranoid, avoidant, schizotypal, dependent and
      narcissistic PDs. Men with OCD were more likely to screen positively for PDs in
      general, cluster A PDs, antisocial, obsessive-compulsive and narcissistic
      categories. The presence of comorbid neuroses in people with OCD had no
      significant effect on the prevalence of PD. CONCLUSIONS: Personality pathology is
      highly prevalent among people with OCD who are living in the community and should
      be routinely assessed, as it may affect help-seeking behaviour and response to
      treatment.

PMID- 16983491
TI  - Professor William Watson Buchanan, MB ChB, MD, FRCP (Glas., Edin., C.), FRACP,
      FRCP (Hon; Ireland), FACR (Hon) (4.7.1930-28.1.2006).

PMID- 16983492
TI  - Current status of the therapeutic uses and actions of the preferential cyclo
      oxygenase-2 NSAID, nimesulide.
AB  - This review summarizes the principal therapeutic responses to the preferential
      COX-2 NSAID, nimesulide, in treating musculo-skeletal joint symptoms and various
      acute and chronic pain conditions and the mode of action in relation to therapy
      in these states. In extensive studies in laboratory animal models and clinical
      trails in patients nimesulide has been found to have potent analgesic, anti
      inflammatory and anti-pyretic activities. It is approved for use in over 50
      countries worldwide (including those in the EU, South and Central America, China,
      India and some other South-East Asia) for the treatment of acute pain, the
      symptomatic treatment of painful osteoarthritis and primary dysmenorrhoea. Its
      mode of action in these states is related to the preferential inhibition of the
      production of cyclo-oxygenase-2 (COX-2) and other inflammatory mediators whose
      production is controlled by stimulation of cyclic-3 ,5'-adenosine monophosphate
      (cAMP); this means that nimesulide is a multi-factorial drug in controlling
      inflammation and pain. The adverse reaction profile of nimesulide is, in general,
      like that of other NSAIDs. It does, however, have relatively low occurrence of
      gastro-intestinal (GI) side effects which is related to its low propensity to
      inhibit the physiologically important COX-1 in the GI mucosa and important
      physicochemical properties (high pKa of 6.5 and lipophilicity) as well as
      inhibiting of mast cell derived histamine and acid secretion in the stomach. In
      contrast with the coxibs, nimesulide has not been found to have appreciable
      cardiovascular toxicity.

PMID- 16983493
TI  - Therapeutic use of cephazolin to prevent complications of spine surgery.
AB  - Discitis, caused by pyogenic organisms, is a potential complication of any
      procedure which involves entering the intervertebral disc during open or
      percutaneous procedures. While there are wide variations in the severity of
      symptoms, the characteristic feature of discitis is the development of
      increasingly severe back pain, which is not relieved by rest, or narcotic
      analgesics. While there is a tendency to spontaneous resolution over time, a self
      limiting course does not always eventuate. Serious complications resulting from
      spread of the infective process can lead to vertebral osteomyelitis or to the
      formation of an epidural abscess with further risk of neural compression.
      Clinical and experimental evidence now supports the prophylactic use of a
      suitable antibiotic, but some uncertainties exist about the benefits of
      antibiotic therapy in treating established discitis. While cephazolin is a widely
      favoured choice of antibiotic, the timing of its administration to prevent or
      treat discitis has been complicated by the lack of suitable methods for detecting
      and measuring the concentration of cephazolin in the plasma and disc in
      experimental and clinical conditions. This paper describes a high-performance
      liquid chromatography technique for detecting the antibiotic cephazolin. The
      results conclude cephazolin can be detected in the plasma and disc after
      administering an intravenous bolus dose. However, concentration of cephazolin in
      the outer disc was 12 times greater than that of the inner disc.

PMID- 16983494
TI  - Porphyromonas gingivalis lipopolysaccharide-induced cytosolic phospholipase A2
      activation interferes with salivary mucin synthesis via platelet activating
      factor generation.
AB  - Liberation of arachidonate from membrane phospholipids by cytosolic phospholipase
      A2 (cPLA2) upon cell activation is considered the key step in generation of
      platelet-activating factor (PAF), a potent lipid messenger recognized as the most
      proximal mediator of inflammatory events triggered by bacterial infection. Here,
      we report on the role of cPLA2 in the disturbances in salivary mucin synthesis
      evoked by the lipopolysaccharide (LPS) of a periodontopathic bacterium, P.
      gingivalis. Using mucous cells of sublingual gland, we show that P. gingivalis
      LPS detrimental effect on salivary mucin synthesis, associated with up-regulation
      in PAF and endothelin-1 (ET-1) generation, was subject to suppression by a
      specific inhibitor of cPLA2, MAFP. Moreover, the LPS-induced changes in mucin
      synthesis and ET-1 generation were countered by PAF receptor antagonist, BN52020.
      The inhibition by PAF antagonist of the LPS-induced reduction in mucin synthesis
      was countered by wortmannin, an inhibitor of PI3K, as well as by ERK inhibitor,
      PD98059. The blockade of ERK caused also inhibition of the LPS-induced cPLA2
      activation and amplification in the impedance capacity of PAF antagonist on the
      LPS-induced ET-1 generation, while the inhibitor of PI3K had no effect. The
      findings are the first to demonstrate that P. gingivalis LPS detrimental effect
      on salivary mucin synthesis involves ERK-dependent cPLA2 activation that leads to
      up-regulation in PAF production and ET-1 generation. We also show that PAF
      receptor activation is a critical prerequisite for the LPS-induced ET-1
      production.

PMID- 16983495
TI  - Paracetamol [acetaminophen]-induced gastrotoxicity: revealed by induced
      hyperacidity in combination with acute or chronic inflammation.
AB  - Paracetamol is regarded as a relatively safe drug in the gastro-duodenal region
      of humans but recent epidemiological investigations have suggested that at high
      doses there may be an increased risk of ulcers and bleeding. To investigate the
      possibility that inflammatory conditions and gastric acidity may play a role in
      potentiating development of gastric mucosal injury from paracetamol in rats (as
      noted previously with various non-steroidal anti-inflammatory drugs) we studied
      the gastric irritant effects of paracetamol and some phenolic and non-phenolic
      analgesics and antipyretics in rats with adjuvant or collagen II induced
      arthritis or zymosan-induced paw inflammation and given 1.0 ml hydrochloric acid
      (HCl) 0.1 M and/or an i. p. injection of the cholinomimetic, acetyl-beta-methyl
      choline chloride 5.0 mg/kg. Gastric lesions were determined 2 h after oral
      administration of 100 or 250 mg/kg paracetamol or at therapeutically effective
      doses of the phenolic or non-phenolic analgesics/antipyretics. The results showed
      that gastric mucosal injury occurred with all these agents when given to animals
      that received all treatments so indicating there is an adverse synergy of these
      three factors, namely: (i) intrinsic disease; (ii) hyperacidity; and (iii) vagal
      stimulation for rapidly promoting gastric damage, both in the fundic as well as
      the antral mucosa, for producing gastric damage by paracetamol, as well as the
      other agents. Removing one of these three predisposing factors effectively
      blunts/abolishes expression of this paracetamol-induced gastrotoxicity in rats.
      These three factors, without paracetamol, did not cause significant acute
      gastropathy.

PMID- 16983496
TI  - Reduced inflammatory potential of peritoneal macrophages recruited in mice
      pretreated with a glycolipid synthesis inhibitor.
AB  - Integral components of mammalian cell membranes, glycosphingolipids (GSL) reside
      in specialized plasma membrane microdomains critical for cell signaling. N
      alkylated nojirimycins are compounds developed for GSL substrate deprivation
      therapy, blocking GSL synthesis by specifically inhibiting an essential enzyme,
      ceramide glucosyltransferase. Peritoneal macrophages recruited in mice pretreated
      with an inhibitory N-alkylnojirimycin displayed a reduced capacity to release
      either TNFalpha or interleukin-6 when re-exposed to whole killed E. coli in
      vitro. Cell viability and protein content were not affected. A nojirimycin
      analogue without GSL inhibitory capacity had no effect. The results show
      inhibition of GSL synthesis in vivo by an N-alkylnojirimycin can reduce the
      response to an inflammatory stimulus and indicate N-alkylnojirimycins have
      experimental and potential clinical value for modulating innate immune responses
      in vivo.

PMID- 16983497
TI  - Arthritic disease suppression and cartilage protection with glycosaminoglycan
      polypeptide complexes (Peptacans) derived from the cartilage extracellular
      matrix: a novel approach to therapy.
AB  - Molecular fragments of cartilage are antigenic and can stimulate an autoimmune
      response. Oral administration of type II collagen prevents disease onset in
      animal models of arthritis but the effects of other matrix components have not
      been reported. We evaluated glycosaminoglycan polypeptides (GAG-P) and matrix
      proteins (CaP) from cartilage for a) mitigating disease activity in rats with
      collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) and b)
      stimulating proteoglycan (PG) synthesis by chondrocytes in-vitro. CIA and AIA
      were established in Wistar rats using standard methods. Agents were administered
      orally (10-200 mg/kg), either for seven days prior to disease induction
      (toleragenic protocol), or continuously for 15 days after injecting the
      arthritigen (prophylactic protocol). Joint swelling and arthritis scores were
      determined on day 15. Histological sections of joint tissues were assessed post
      necropsy. In chondrocyte cultures, CaP + / - interleukin-1 stimulated PG
      biosynthesis. CaP was also active in preventing arthritis onset at 3.3, 10 or 20
      mg/kg in the rat CIA model using the toleragenic protocol. It was only active at
      20 and 200 mg/kg in the CIA prophylactic protocol. GAG-P was active in the CIA
      toleragenic protocol at 20 mg/kg but chondroitin sulfate and glucosamine
      hydrochloride or glucosamine sulfate were all inactive. The efficacy of CaP in
      the rat AIA model was less than in the CIA model. These findings lead us to
      suggest that oral CaP could be used as a disease-modifying anti-arthritic drug.

PMID- 16983498
TI  - Protective effects of nedocromil sodium and sodium cromoglycate on gastroduodenal
      ulcers: a comparative study in rats.
AB  - Stabilization of mast cells plays a key mechanism to protect gastrointestinal
      tract from injury. This study presents a comparative evaluation of mast cell
      stabilizers nedocromil sodium (NDS) and sodium cromoglycate (SCG) in experimental
      gastric and duodenal ulcers in rats. Wistar rats of either sex were used in this
      study. Both NDS and SCG, in the doses of 10, 30 and 100 mg/kg were given
      intraperitoneally for gastric secretion studies and by gavage for antiulcer
      studies. Acid secretion studies were undertaken in pylorus-ligated rats. Gastric
      lesions were induced by water immersion restraint stress (WIRS), indomethacin and
      ethanol whereas duodenal ulcers were produced by cysteamine. The level of
      glutathione (GSH) and gastric wall mucus were measured in glandular stomach of
      rats following ethanol-induced gastric lesions. SCG was more effective than NDS
      in preventing WIRS- and indomethacin-induced gastric lesions whereas reverse was
      true in ethanol- and cysteamine-induced ulcers. All the 3 doses of SCG offered
      almost equal protection against WIRS-induced gastric lesions whereas only medium
      and high dose of NDS provided significant protection in this model of ulcer. NDS
      significantly inhibited cysteamine-induced duodenal ulcers whereas SCG failed to
      do so. Pretreatment with NDS or SCG significantly and dose-dependently protected
      gastric mucosa against ethanol-induced injury, while the former drug appeared to
      be more effective. The cytoprotective effects of these two drugs were accompanied
      by the attenuation of ethanol-induced depletion of gastric wall mucus and GSH.
      The differential effects of NDS and SCG against various gastric lesions
      rationalize the possible benefits of a combined therapy (NDS+SCG) for the
      treatment of complex gastroduodenal ulcers.

PMID- 16983499
TI  - Steadiness of quadriceps contractions in young and older adults with and without
      a history of falling.
AB  - Decreased steadiness of muscle force may be associated with ageing and could be a
      cause of falls in older people. We studied this in isometric and anisometric
      quadriceps contractions in healthy young and older people. The older group
      contained people with and without a history of medically unexplained falls. Forty
      four young (aged 18-40 years) and 78 older (aged > 70 years) subjects
      participated. In the latter group 34 people had a history of falling (fallers)
      and 44 did not (non-fallers). Isometric steadiness was measured by the
      coefficient of variation (CoV) of force at 10, 25 and 50% maximal voluntary force
      (MVC). Anisometric steadiness was measured by the SD of acceleration during
      concentric and eccentric contractions against two external loads (1 and 5 kg).
      There was an overall trend for the younger subjects to be most steady and the
      fallers the least but the differences were not consistently significant.
      Isometric steadiness was unaffected by force in all groups. The fallers were less
      steady (P < 0.001) than both the young and non-fallers, who had similar values.
      During anisometric contractions, steadiness was similar with both external loads
      and types of contraction in all groups. During dynamic contractions the older
      subjects were less steady (P < 0.002). Only eccentric contractions distinguished
      between the two older groups, with the fallers being less steady by 31% (P =
      0.013). These data indicate ageing per se is associated with decreased
      anisometric, but not isometric, steadiness. Greater unsteadiness during eccentric
      contractions in the fallers could be an important mechanism of medically
      unexplained falls.

PMID- 16983501
TI  - The effect of oxysterols, individually and as a representative mixture from food,
      on in vitro cultured bovine ovarian granulosa cells.
AB  - The cytotoxicity of five oxysterols identified in cooked fish, 7-ketocholesterol,
      7beta-hydroxycholesterol, cholesterol 5alpha,6alpha-epoxide, cholestanetriol and
      4-cholesten-3-one, was investigated in primary cultures of bovine ovarian
      granulosa cells. Cells were exposed to the oxysterols individually and to a
      mixture of the same oxysterols for 24 h. Cell viability as determined by trypan
      blue exclusion and mitochondrial integrity (3-[4,5-dimethylthiazol-2yl]-2,5
      diphenyltetrazolium bromide (MTT) reduction) was reduced by 0.5 and 2.5 microM
      7beta-hydroxycholesterol, cholesterol 5alpha,6alpha-epoxide, cholestanetriol and
      4-cholesten-3-one, but not by 0.5 or 2.5 microM 7-ketocholesterol under the same
      culture conditions. A mixture of 7-ketocholesterol, 7beta-hydroxycholesterol,
      cholesterol 5alpha,6alpha-epoxide, cholestanetriol and 4-cholesten-3-one 0.5
      microM each; 2.5 microM oxysterol in total) did not change cell viability
      relative to controls. Lipid peroxidation, as determined by thiobarbituric acid
      reactive substances assay, was unaffected by a 24-hour exposure of granulosa
      cells to individual oxysterols but was increased slightly by the oxysterol
      mixture. The specific activities of antioxidant enzymes superoxide dismutase and
      catalase were increased to different extents (1.17- to 6.43-fold), relative to
      controls, by the administration of individual oxysterols and the oxysterol
      mixture. These results indicate that while some individual oxysterols can induce
      cytotoxic effects and defensive responses in bovine ovarian granulosa cells,
      administration of the same oxysterols as a mixture does not elicit the same
      responses. In addition, the oxysterols tested exerted a pro-apoptotic effect on
      granulosa cells when administered individually at concentrations of 0.5 and 2.5
      microM, but not when administered as a 2.5 microM oxysterol mixture. The results
      suggest that major oxysterols are not universally cytotoxic, they may complete
      with other oxysterols for receptor sites, and that the simultaneous presence of
      several different oxysterol species may reduce the adverse effects of individual
      oxysterols.

PMID- 16983502
TI  - Evaluation of alpha-glutathione-S-transferase as a biomarker of lamivudine
      therapy for chronic hepatitis B.
AB  - Hepatic damage associated with chronic hepatitis B (CHB) relies on measurement of
      serum transaminases and asssessment of hepatic histology. We determined if serum
      hepatic function tests, including alpha-glutathione-S-transferase ((GST), were of
      value in monitoring or predicting the effect of lamivudine therapy for CHB.
      Thirty-nine patients received orally 100 mg of lamivudine daily for 48 weeks.
      Blood samples were obtained at baseline and at 24 and 48 weeks. At the end of the
      treatment period the patients were then divided into four groups according to the
      pattern of HBs and HBe antigens. At baseline and at 24 weeks ALT, AST, and (GST
      had lower values in the complete response compared to the complete failure
      groups. Using ROC analysis, only ALT at 24 weeks (area under the curve = 0.803)
      had significant diagnostic ability in detecting responders. These results
      reaffirm the value of measuring serum ALT as an indicator of treatment response
      and provide information on the potential use of (GST as an additional prognostic
      biomarker in this patient group.

PMID- 16983503
TI  - The effect of caffeic acid phenethyl ester on bacterial translocation and
      intestinal damage in cholestatic rats.
AB  - We investigated the effect of caffeic acid phenethyl ester in rat ileum injury
      induced by chronic biliary obstruction. Swiss albino rats were divided into three
      groups: Group 1, sham (n = 7); Group 2, common bile duct ligation (n = 7); and
      Group 3, common bile duct ligation plus caffeic acid phenethyl ester (n = 7). In
      the caffeic acid phenethyl ester-treated rats, ileum tissue levels of
      malondialdehyde and myeloperoxidase were significantly lower than those of the
      bile duct-ligated rats (P < 0.001). The levels of tumor necrosis factor-alpha,
      interleukin-6, and interleukin-1alpha in the caffeic acid phenethyl ester group
      were significantly lower than those in the bile duct ligation group (P < 0.03, P
      < 0.01, and P < 0.02 respectively). The present study demonstrates that
      intraperitoneal administration of caffeic acid phenethyl ester in bile duct
      ligated rats reduces intestinal oxidative stress. This effect may be useful in
      the preservation of intestinal damage in cholestasis.

PMID- 16983505
TI  - Pelvic floor muscle biofeedback in the treatment of urinary incontinence: a
      literature review.
AB  - Biofeedback is efficacious in the training of the pelvic floor musculature in
      order to enhance continence. This article reviews the anatomy and physiology of
      micturition as the underlying rationale for pelvic floor muscle biofeedback in
      the treatment of urinary incontinence. It critically reviews 28 studies published
      in peer reviewed journals from 1975 to 2005 that were prospective, randomized
      studies with parametric statistical analyses, operationally defined patient
      selection criteria, treatment protocols and outcome measures. The overall mean
      treatment improvement for patients undergoing biofeedback for urinary
      incontinence was 72.61%. In 21 of 35 (60%) paired comparisons, biofeedback
      demonstrated superior symptomatic outcome to control or alternate treatment
      groups. Larger studies and a standardization of technology and methodology are
      required for more conclusive determinations.

PMID- 16983504
TI  - Neuroimmune link in the mucosa of chronic gastritis with Helicobacter pylori
      infection.
AB  - It is suggested that different neuropeptides regulate gastric mucosal integrity
      and participate in the development of chronic gastritis. The aim of this study
      was to examine the roles and changes of immunoreactive (IR) nerves and
      immunocompetent cells in human gastritis. Immunohistochemical,
      immunocytochemical, and confocal laser microscopic methods were used. All
      investigated nerve fibers were found in different quantities in the mucosa of
      both control and gastritis samples. The number of SP, NPY, and VIP IR nerve
      fibers increased significantly (P < 0.05) in gastritis. No IR immunocompetent
      cells (lymphocytes, plasma cells, mast cells) were found in the control, however,
      some showed NPY (16.8%) and SP (9.4%) immunoreactivity in chronic gastritis. The
      distance between nerve fibers and immunocompetent cells was 200 nm to 1 microm.
      In conclusion, the increased number of SP, NPY, and VIP IR nerves and IR
      immunocytes suggests that they participate in development of neurogenic
      inflammation, repairing processes of chronic gastritis.

PMID- 16983506
TI  - A Phase II study of SU5416 in patients with advanced or recurrent head and neck
      cancers.
AB  - BACKGROUND: SU5416 (semaxanib) is a synthetic small molecule inhibitor of the
      tyrosine kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2).
      This Phase II study was conducted to determine the safety and efficacy of SU5416
      in patients with recurrent or metastatic head and neck cancers. PATIENTS AND
      METHODS: This was an open label, single arm, Phase 2 study for patients who had
      received no more than 2 cytotoxic regimens. Thirty-five patients received
      intravenous SU5416 (145 mg/m(2)) twice per week by intravenous catheter.
      Radiologic imaging for response assessment was planned at the conclusion of each
      8 week cycle. Serum VEGF levels and power Doppler ultrasound tumor imaging were
      explored as potential surrogate markers for SU5416 activity. RESULTS: Thirty-two
      patients had received prior radiotherapy, including 18 patients who received
      prior concurrent chemoradiotherapy. Twelve patients had received prior
      chemotherapy in the recurrent disease setting. Thirty-one patients were evaluable
      for response. There was one partial response and one minor response. The median
      number of 8-week cycles received was 1 (range 1-4). Median overall survival was
      6.25 months. The most common > or = grade 3 toxicity was headache (31%). There
      was one fatal carotid artery hemorrhage. Fatigue, nausea, and vomiting were
      common grade 1-2 adverse events. Power Doppler ultrasound demonstrated decreased
      tumor vascularity in 5 of 7 patients. CONCLUSIONS: Treatment with SU5416 in
      patients with head and neck cancers is feasible, but objective responses are
      rare. Studies evaluating more potent anti-angiogenic agents in this disease are
      of interest.

PMID- 16983507
TI  - Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients
      with advanced colorectal cancer: final results of a randomised, controlled,
      multicenter phase II study.
AB  - BACKGROUND: Oxaliplatin-induced neurotoxicity is a growing, relevant clinical
      problem. In this study we evaluated the efficacy and safety of carbamazepine for
      prevention of oxaliplatin-associated neuropathy in patients with advanced
      colorectal cancer. METHODS: Chemotherapeutic treatment consisted of oxaliplatin
      85 mg/m(2) given biweekly and weekly folinic acid 500 mg/m(2) followed by a 24-h
      infusion of 5-FU 2000 mg/m(2) (FUFOX). One cycle consisted of six consecutive
      weeks of treatment followed by two weeks of rest (=Treatment B). For Treatment A
      carbamazepine was added in a dosage for targeted plasma levels of 4-6 mg/L.
      Neurotoxicity was regularly assessed using a specific scale. Moreover, an
      evaluation of chronic sensory symptoms and a neurologic examination including
      tests for vibrational sense, strength and deep tendon reflexes were added
      creating a peripheral neuropathy (PNP) score. RESULTS: The prospectively defined
      adequate number of patients needed to provide power for the primary outcome could
      not be achieved. 19 patients were assigned to Treatment A and 17 to Treatment B.
      At baseline, the distribution of all clinicopathologic variables was comparable
      between the two groups. Overall response rates were 16% and 24% and overall
      survival 15.1 months and 17.4 months for Treatment A and Treatment B,
      respectively. Between Treatment A and Treatment B there were no major differences
      when considering worst neurotoxicity during the study period (p=0.46). Grade 3/4
      neurotoxicity occured in 4 patients with Treatment A vs. 6 patients with
      Treatment B. There were no major differences between both groups in each category
      of the PNP score. CONCLUSIONS: Based on the small number of patients and low
      statistical power of our study definite conclusions regarding efficacy and safety
      of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients
      with advanced colorectal cancer cannot be drawn.

PMID- 16983508
TI  - A phase II study of PS-341 (Bortezomib) in advanced or metastatic urothelial
      cancer. A trial of the Princess Margaret Hospital and University of Chicago phase
      II consortia.
AB  - BACKGROUND: Based on evidence of activity in epithelial tumors in preclinical and
      Phase I studies, its novel mechanism of action, and its tolerability we undertook
      a study of bortezomib [PS-341], a reversible proteasome inhibitor, for patients
      with advanced or metastatic urothelial cancer. PATIENTS AND METHODS: Patients
      with advanced or metastatic unresectable urothelial carcinoma were enrolled onto
      this multicenter, phase II trial. Patients with measurable disease were treated
      with bortezomib 1.3 mg/m2/day (twice weekly for 2 weeks out of 3) by intravenous
      infusion on days 1, 4, 8, and 11 every 21 days. A two stage phase II design was
      used. RESULTS: Twenty-one patients were enrolled and twenty were eligible and
      received treatment. Eighty-five percent of patients had previous chemotherapy
      regimens. No objective responses were observed, median time-to-progression was
      8.1 weeks (95% confidence interval [CI] 6.4 to 9), and median overall survival is
      estimated to be 15 weeks (95% CI 3.6 - NA). A total of 15 patients experienced a
      grade 3-4 adverse event. The most common were alkaline phosphatase (20%
      patients), lymphopenia (20% patients), myalgia (15% patients), dyspnea (15%
      patients) and thrombosis/embolism (15% patients). CONCLUSION: Single-agent
      bortezomib is an ineffective treatment for progressive-cisplatin-refractory
      urothelial carcinoma and should not be considered for future clinical trials in
      this population of patients.

PMID- 16983509
TI  - Effect of polystyrene microsphere surface to fluorescence lifetime under two
      photon excitation.
AB  - Molecular assays such as immunoassays are often performed using solid carriers
      and fluorescent labels. In such an assay format a question can be raised on how
      much the fluorescence of the label is influenced by the bio-affinity binding
      events and the solid carrier surface. Since changes in fluorescence intensity as
      labels bind to surfaces are notoriously difficult to quantify other approaches
      are preferred. A good indicator, independent of the fluorescence intensity of the
      label, is the fluorescence lifetime of the marker fluorophore. Changes in
      fluorescence lifetime reliably indicate the presence of dynamic quenching, energy
      transfer or other de-excitation processes. A microsphere based assay system is
      studied under two-photon excitation. Changes in fluorescence lifetime are studied
      as labeled protein conjugates bind on microsphere surfaces--both direct on the
      surface and with a few nanometer distance from the surface. Fluorescence signal
      is measured from individual polystyrene microspheres and the fluorescence
      lifetime histogram is simultaneously recorded. The results indicate that self
      quenching and quenching by the polystyrene surface are both present in such a
      system. However, the effect of the surface can be avoided by increasing the
      distance between the surface and the label. Typical distances achieved by a
      standard sandwich type of assay, are already sufficient to overcome the surface
      induced quenching in fluorescence detection.

PMID- 16983510
TI  - Sensitive determination of norfloxacin by the fluorescence probe of terbium (III)
      sodium dodecylbenzene sulfonate and its luminescence mechanism.
AB  - The fluorescence system of the norfloxacin-Tb3+- sodium dodecylbenzene sulfonate
      (SDBS) was investigated in this paper. The experiments indicated that the
      fluorescence intensity of the Tb3+-SDBS was greatly enhanced by the norfloxacin.
      On the basis of the above findings, a sensitive fluorimetric method for
      determining the norfloxacin was established. The fluorescence intensity was
      measured by a 1-cm quartz cell with the excitation wavelength of 290 nm and the
      emission wavelength of 545 nm. The enhanced fluorescence intensity of the system
      (Delta F) showed a good linear relationship with the concentration of norfloxacin
      in the range of 5.0x10(-9) mol L(-1)-2.0x10(-6) mol L-1, its correlation
      coefficient was 0.9991 and the detection limit (S/N=3) was 1.2x10(-9) mol L-1.
      The presented method was used to determine the norfloxacin in real pharmaceutical
      samples. The luminescence mechanism was also discussed in detail. In the
      fluorescence system of the norfloxacin-Tb3+-SDBS, the SDBS not only acted as the
      surfactant, but also acted as the energy donor.

PMID- 16983511
TI  - Luminescence characterisation of the reaction system histidine-KBrO3-Tb(III)
      H2SO4.
AB  - Chemiluminescence of the system containing Tb(III) ions, histidine and bromate
      ions in acid solution was studied. The kinetic curves and CL emission spectra of
      the system were discussed. The emission spectrum of the histidine-Tb(III)-KBrO3
      H2SO4 system revealed two emission maxima at approximately 490 and 550 nm,
      characteristic of Tb(III) ions. Values of lifetimes of the Eu(III) excited states
      in Eu(III)-histidine system have shown that the histidine formed ML and ML2
      complexes in neutral solution and did not make them in acidic environment. On the
      basis of the results, a possible mechanism of reaction system: histidine-Tb(III)
      KBrO3-H2SO4 is presented.

PMID- 16983512
TI  - Cultivating systemic capacity: the Rhode Island tobacco control enhancement
      project.
AB  - This paper describes the Rhode Island Tobacco Control Enhancement Project (TCEP),
      a state-university-community technical assistance system. TCEP was developed
      under the auspices of the Rhode Island Department of Health's Tobacco Control
      program and was designed to build capacity among nine community-based
      organizations to mount comprehensive tobacco control interventions in five
      diverse communities within the state. This paper: (1) provides a description of
      community mobilization; (2) presents a logic model for planning and decision
      making used by state-university-community partners; (3) describes training,
      technical assistance services and implementation; and, (4) describes the
      evaluation and program improvement activities used to support on-going project
      development.

PMID- 16983513
TI  - Computerized performance monitoring systems: learning and living with its
      limitations.
AB  - Computer technology now allows clinical administrators to collect and analyze
      large data sets for performance monitoring. Despite the obvious usefulness of
      this technology, there are limitations. The indices that we can measure are at
      best proxies that might correlate with good clinical care but can also become
      dissociated from it in a variety of ways. First, there may not be a relationship
      throughout the entire continuum between the indicator and what we really value.
      Second, change in an indicator may not be associated with comparable change in
      the underlying value. Thirdly, the valence of an indicator can change depending
      on the context. Fourth, the very act of measuring an indicator can change its
      valence. Although, from a research perspective there may be technical solutions
      to these problems, in the real world where clinical care and politics meet, this
      may not be possible. Indices become reified. Measures become benchmarks and
      benchmarks quotas. Average is not a statistical phrase but a judgment and below
      average a term of approbation. To maximize the benefits of computerized
      monitoring, administrators need to be sensitive to this political dimension.

PMID- 16983515
TI  - Effect of tumor-derived cytokines and growth factors on differentiation and
      immune suppressive features of myeloid cells in cancer.
AB  - It is well established that cancers affect differentiation of dendritic cells and
      promote systemic expansion of immune suppressive immature myeloid cells. This
      phenomenon may represent a mechanism of tumor escape from immune attack and could
      have significant impact on tumor progression. In this review we discuss the role
      of different tumor-derived factors, which were implicated in abnormal myeloid
      cell differentiation. The role of reactive oxygen species as well as JAK/STAT
      signaling in mechanisms of the effects of tumor-derived factors on myeloid cells
      is also discussed.

PMID- 16983516
TI  - Social sex selection and the balance of the sexes: empirical evidence from
      Germany, the UK, and the US.
AB  - Preconception sex selection for nonmedical reasons is one of the most
      controversial issues in bioethics today. The most powerful objection to social
      sex selection is based on the assumption that it may severely distort the natural
      sex ratio and lead to a socially disruptive imbalance of the sexes. Based on
      representative social surveys conducted in Germany, the United Kingdom, and the
      United States, this paper argues that the fear of an impending sex ratio
      distortion is unfounded. Given the predominant preference for a "gender balanced
      family," a widely available service for social sex selection is highly unlikely
      to upset the balance of the sexes in Western societies.

PMID- 16983517
TI  - Regulated family balancing by equalizing the sex-ratio of gender-selected births.

PMID- 16983518
TI  - Optimization of endometrial preparation results in a normal endometrial function
      test (EFT) and good reproductive outcome in donor ovum recipients.
AB  - PURPOSE: Numerous studies have investigated potential markers of endometrial
      receptivity as predictors of successful implantation. Cyclin E and p27 have
      recently been studied using the endometrial function test (EFT). Our objective is
      to determine the correlation between the expression of cyclin E and p27 and the
      adequacy of uterine preparation of recipients using donor oocytes. METHODS:
      Twenty recipients undergoing preparatory cycles with leuprolide acetate,
      estrogen, and progesterone. Endometrial biopsies were obtained 10-12 days after
      progesterone supplementation following the course of estrogen. The tissue was
      prepared for histological analysis and immunohistochemical staining for cyclin E
      assessment. The outcome of their subsequent ovum donation cycle was blinded to
      the reviewer of the EFT. RESULTS: All recipients showed normal luteal
      transformation. Nineteen (95%) of the recipients had a normal EFT. This is
      significantly higher than what we demonstrated, previously, in unexplained
      infertility patients, where only 40% of such patients had a normal EFT. Thirteen
      recipients with a normal EFT had a clinical pregnancy, while 6 did not become
      pregnant in their subsequent transfer cycles. The sole patient with an abnormal
      EFT did not conceive on 2 subsequent cycles. CONCLUSIONS: While a normal EFT does
      not guarantee a successful pregnancy, an abnormal EFT appears to be associated
      with pregnancy failure. This may be useful in identifying women who need
      adjustments to their stimulation protocols prior to progressing to a physically,
      emotionally, and financially costly cycle.

PMID- 16983519
TI  - Extended estrogen administration for women with thin endometrium in frozen-thawed
      in-vitro fertilization programs.
AB  - PURPOSE: To evaluate the effect of extended estrogen administration for women
      with thin endometrium in frozen-thawed in-vitro fertilization (IVF) programs.
      METHODS: Thirty-six women undergoing IVF program had thin endometrium (<8 mm).
      Among them, 23 received fresh embryo transfer (control group), but 13 canceled
      embryo transfer and underwent frozen-thawed embryo transfer in the subsequent
      cycle after extended administration of exogenous estrogen (study group). RESULTS:
      In the study group, the mean endometrial thickness increased significantly from
      6.7 mm in controlled ovarian hyperstimulation cycles to 8.6 mm after an extended
      estrogen therapy for 14 to 82 days (P=0.031). Their pregnancy rate was
      significantly higher than that in the control group (38.5% vs. 4.3%, P=0.016).
      Among 5 women achieving pregnancies in the study group, one was complicated with
      placenta accreta, and the other 4 had uneventful pregnancies. CONCLUSIONS:
      Extended estrogen administration followed by frozen-thawed IVF programs is
      beneficial for women with thin endometrium. However, the risk of abnormal
      placentation and peripartal complication should be kept in mind.

PMID- 16983521
TI  - Economic evaluation of Durogesic in moderate to severe, nonmalignant, chronic
      pain in Germany.
AB  - We carried out a cost-effectiveness evaluation of transdermal fentanyl compared
      to three other widely used opioids: transdermal buprenorphine, sustained-release
      morphine, and controlled-release oxycodone from a third-party-payers perspective.
      A decision analytic model with data from a structured database search and from
      panel data and assumptions was used to derive both cost and utility results.
      Probabilistic sensitivity analysis was performed to ensure the findings.
      Transdermal fentanyl patients gain more quality adjusted life-days or quality
      adjusted life-years per euro. The incremental cost per quality-adjusted life-year
      is 1,625.65 euro for transdermal fentanyl compared to sustained-release morphine
      and 1,003.03 euro compared to CO, and it is cost-saving compared to transdermal
      buprenorphine (-203.38 euro per patient). Transdermal fentanyl is thus cost
      effective compared to both sustained-release morphine and CO and dominant
      compared to transdermal buprenorphine in the treatment of adults with
      nonmalignant moderate to severe chronic pain.

PMID- 16983520
TI  - Impact of physician performing embryo transfer on pregnancy rates in an assisted
      reproductive program.
AB  - PURPOSE: To evaluate the effect of the individual physician performing embryo
      transfer, on clinical pregnancy rates. METHOD: Data from a total of 485
      consecutive embryo transfers performed on 485 women aged 23-37 years were
      prospectively collected for this study. All patients underwent a standard
      downregulation long protocol for ovarian stimulation. Oocyte recovery was
      performed at 36 h after hCG administration. Embryo transfer took place at 48 h
      after insemination. The patients were matched in two groups that have been linked
      to two different ET providers (A and B). The same method of loading embryos into
      the embryo transfer catheter was used. RESULTS: Clinical pregnancy rates varied
      significantly (p< or =0.01) between the two providers: 36.1% in group A and 20.6%
      in group B. The number and quality of embryos transferred did not differ between
      the groups. CONCLUSION: The results suggest that the physician factor may be an
      important variable in embryo transfer technique.

PMID- 16983522
TI  - The demand for private health care under national health insurance: the case of
      the self-employed.
AB  - This study explores the demand for private health care and supplemental health
      insurance in Israel, where universal national health insurance provides all
      inhabitants with a standard package of medical care. Our theoretical model and
      empirical study follow research previously conducted in four other countries. It
      was found that the self-employed in Israel demand more private health services
      and supplemental health insurance than wage-earners. Income, age, education,
      health status, marital status, origin, and profession were found to play a part
      in explaining these demands.

PMID- 16983524
TI  - Long-term results of surgery in childhood glaucoma.
AB  - PURPOSE: The aim of this study is to assess the functional results and
      morphological parameters in children surgically treated for glaucoma. METHODS:
      Data from 43 patients and 68 eyes who were operated in our department between
      1990 and 2002 were collected. This retrospective trial included primary
      congenital glaucoma (n=36), and secondary glaucoma (n=7) in Rieger-Axenfeld
      syndrome and Sturge Weber syndrome. Intraocular pressure (IOP), axial length of
      the eyeball, visual acuity, refractive errors and orthoptic status were analysed.
      RESULTS: The age of patients at the first surgery was 6.0 +/- 5.3 months (range
      0.7 to 28.0 months). The mean period of follow-up was 57.3 +/- 36.8 months (6.0
      161.0). The mean number of surgical procedures performed on one eye was 2.5 +/-
      2.4 procedures (1-11). The mean IOP before the first surgery was 31.0 +/- 7.9
      mmHg (17.5-52.0), and was 15.0 +/- 3.9 mmHg (7.0-28.0) at the last visit. 49 eyes
      (72.1%) did not need any further medical treatment after the last surgical
      procedure. The IOP was 18 mmHg or lower without medication in 29 eyes (42.6%)
      after just one surgical procedure (21 trabeculotomy, 8 combined
      trabeculotomy/trabeculectomy with or without mitomycin-C). At the first
      examination, the mean axial length of the eyeball was 22.6 +/- 1.8 mm (the mean
      normal value at this age is 20.3 +/- 0.7 mm), and was 24.4 +/- 2.0 mm at the last
      visit (the mean normal value at this age is 22.2 +/- 0.6 mm). The best corrected
      visual acuity at the last visit was 0.25 +/- 4.6 lines; the normal range of
      visual acuity at this age is from 0.4 +/- 4.0 lines to 0.8 +/- 3.0 lines. Visual
      acuity was 0.32 or more in 53.0% of the eyes. Visual acuity was lower than 0.1 in
      only 15.2% of the eyes. Myopia was present in 57.4% of the eyes with a mean
      spherical equivalent of -6.1 +/-3.9 dioptres. 15 patients (34.9%) developed
      strabismus. 22 patients (51.2%) were treated with part-time occlusion. Binocular
      function as assessed with the Lang-1 test was positive in 17 of 30 patients
      (56.7%). CONCLUSIONS: Although a good long-term IOP-control can often be achieved
      in childhood glaucoma, the visual acuity remains below the normal range in most
      cases despite close orthoptic follow-up.

PMID- 16983525
TI  - Tumor lysis syndrome as a contributory factor to the development of reversible
      posterior leukoencephalopathy.
AB  - INTRODUCTION: Reversible posterior leukoencephalopathy syndrome (RPLS) is a
      recently described clinical and radiological entity comprising headache,
      seizures, altered level of consciousness and visual disturbances in association
      with transient posterior cerebral white-matter abnormalities. METHOD: We report a
      young woman with Burkitt's lymphoma who developed RPLS after combined
      chemotherapy administered during the tumor lysis syndrome. RESULTS: The symptoms
      in this patient fitted well with those of RPLS; they included abrupt alterations
      in mental status, seizures, headache, visual changes and characteristic
      neuroradiological findings. She was given further combination chemotherapy
      without any neurological complications, at which time she had already recovered
      from both RPLS and tumor lysis syndrome. CONCLUSION: Although many etiological
      factors have been reported in the development of RPLS, the underlying mechanism
      is not yet well understood. With prompt and appropriate management, RPLS is
      usually reversible, and chemotherapy can be continued after complete recovery
      from RPLS. We suggest that tumor lysis syndrome should be considered as a
      contributory factor to the development of RPLS in patients for whom treatment
      with combined chemotherapy for hematological malignancies is planned.

PMID- 16983526
TI  - Nitrogen removal in a wastewater treatment plant through biofilters: nitrous
      oxide emissions during nitrification and denitrification.
AB  - In order to estimate N(2)O emissions from immersed biofilters during nitrogen
      removal in tertiary treatments at urban wastewater treatment plants (WWTPs), a
      fixed culture from the WWTP of "Seine Centre" (Paris conurbation) was subjected
      to lab-scale batch experiments under various conditions of oxygenation and a
      gradient of methanol addition. The results show that during nitrification, N(2)O
      emissions are positively related to oxygenation (R (2) = 0.99). However, compared
      to the rates of ammonium oxidation, the percentage of emitted N(2)O is greater
      when oxygenation is low (0.5-1 mgO(2) L(-1)), representing up to 1% of the
      oxidized ammonium (0.4% on average). During denitrification, the N(2)O emission
      reaches a significant peak when the quantity of methanol allows denitrification
      of between 66% and 88%. When methanol concentrations lead to a denitrification of
      close to 100%, the flows of N(2)O are much lower and represent on average 0.2% of
      the reduced nitrate. By considering these results, we can estimate, the emissions
      of N(2)O during nitrogen removal, at the "Seine Centre" WWTP, to approximately 38
      kgN-N(2)O day(-1).

PMID- 16983527
TI  - The effect of bioaugmentation on the performance of sequencing batch reactor and
      sludge characteristics in the treatment process of papermaking wastewater.
AB  - In this paper, the differences between reinforced sequencing batch reactor, which
      was inoculated with superior mixed flora, and conventional sequencing batch
      reactor were compared in the process of treating papermaking wastewater under
      similar conditions. The results showed that the addition of superior mixed flora
      could not only shorten the sludge acclimation time, but also improve the
      treatment efficiency of reactor as well as make the reactor have higher ability
      to withstand high volume loading rate; the phenomenon of aerobic granulation only
      occurred in reinforced sequencing batch reactor, and superior mixed flora were
      the key reason that aerobic granular sludge could shape; aerobic granular sludge
      had many advantages over conventional activated sludge such as it possessed
      compacter microbial structure, better settling performance, and lower water
      content.

PMID- 16983528
TI  - [Prevention of local recurrence using adjuvant radiotherapy after radical
      prostatectomy. Indications, results, and side effects].
AB  - Depending on the tumor stage, 15-60% of patients develop a rise in PSA from
      levels around zero following radical prostatectomy. It is unclear whether this
      involves a local, systemic, or a mixed form of local/systemic progression. In
      addition to a multitude of retrospective studies, the results of three randomized
      trials are available that have already been published in full or in abstract
      form. For pT3 prostate cancer with extraprostatic extension, data are available
      from three randomized trials that consistently evidence an absolute decrease in
      biochemical progression rate of 20% after 4-5 years. These findings confirm the
      results of numerous retrospective studies. The large majority of authors employ
      total radiation doses of 60 Gy with single doses of 2 Gy. One randomized trial
      has shown that an increased local control rate is the basis for prolonged
      biochemical progression-free survival. The rate of acute and late radiation
      sequelae after three-dimensionally planned prostatic fossa radiotherapy (RT) with
      60 Gy is very low; the rate of more severe late sequelae is <2%. Data on the
      status of pT2 prostate cancer with positive surgical margins are worse. The
      current findings are controversial and require further investigations. Basically,
      however, adjuvant RT is also possible for pT2 cancers with positive surgical
      margins. The efficacy of adjuvant RT for patients with positive surgical margins
      of pT3 carcinomas, whether or not they achieve PSA levels around zero, has been
      substantiated. A prolongation of survival time has, however, not yet been
      established because the follow-up period is too short. Randomized trials are
      still needed for cases of organ-confined prostate cancer (pT2 R1). It is unclear
      whether adjuvant RT is superior to RT when PSA levels increase beyond zero after
      radical prostatectomy. Randomized trials addressing this issue are still lacking.

PMID- 16983529
TI  - [Salvage radical prostatectomy].
AB  - BACKGROUND: Following external beam radiation and interstitial radiation for
      prostate cancer, between 30% and 50% of the patients experience locoregional
      recurrence of their cancer. Although radical salvage prostatectomy is a secondary
      treatment option with curative intent, so far only a few hundred patients (<2%)
      worldwide have undergone this operation. The subject of this paper is a review of
      the world literature with reference to the frequency with this operation is
      performed and the technique, and also the prospects of success and possible
      complications. PATIENTS AND METHODS: After radiotherapy, approximately 30% of
      biopsies are positive. Nonetheless, only 536 cases of salvage radical
      prostatectomy had been reported in the world literature up to 2005. The diagnosis
      of a local recurrence was always confirmed by rectal punch biopsy, pelvic CT and
      bone scintigraphy. Salvage radical prostatectomy with or without nerve sparing,
      with pelvic lymphadenectomy and, in some patients with cystectomy plus urinary
      diversion was the operative treatment applied. RESULTS: Following secondary
      treatment after radiotherapy (RT), three parameters have been consistently
      identified as predictors of local failure: PSA nadir, time to nadir and PSA
      doubling time; clinical stage and type of first-line treatment are not helpful in
      predicting failure. The 5-year biochemical relapse-free survival rates are 77%,
      71% and 28% for stages pT2, pT3a and pT3b/pN1, respectively. The success rate for
      salvage radical prostatectomy is thus similar to that for de novo radical
      prostatectomy for the same stages. In the past salvage radical prostatectomy
      following radiotherapy had a high complication rate. CONCLUSIONS: A salvage
      radical prostatectomy with curative intent is a radical prostatectomy following
      radiotherapy also performed with curative intent. The reasons for the few
      literature reports of salvage RPX are: (1) oncological misgivings (too long a
      period of observation of PSA by the radiation oncologist/urologist; (2)
      misgivings to do with surgical technique, as the operation is technically
      challenging and involves a high risk of complications, especially incontinence.
      In recent times the comorbidity rate has become acceptable in cases in which the
      indications have been correctly observed. We believe that salvage prostatectomy
      should be considered only for patients in good general health whose life
      expectancy is over 10 years and who have recurrent cancer confirmed by punch
      biopsy 1 year or longer after the completion of radiotherapy and whose cancer was
      initially in an early (T1-2) clinical stage before their radiotherapy. Ideally,
      serum PSA should be less than 10 ng/ml both initially (before radiotherapy) and
      before salvage surgery. In addition, patients should be highly motivated and able
      to accept the surgical morbidity (50% incontinence rate).

PMID- 16983530
TI  - Anaplastic large-cell non-Hodgkin's lymphoma of the breast in periprosthetic
      localisation 32 years after treatment for primary breast cancer--a case report.
AB  - Primary, as well as secondary, lymphomas of the breast are rare diseases and
      might, in some cases, be misdiagnosed as breast cancer on routine
      hematoxylin/eosin stainings. We report a case of an anaplastic large cell
      lymphoma in a 72-year-old woman with a history of breast cancer treated with
      breast-ablative surgery and a subsequent silicon implant 32 years ago.
      Clinically, she presented with an ulceration of the skin, which had developed
      within a few months. On conventional histology, the tumor cells were mimicking
      poorly differentiated invasive ductal carcinoma with a prominent leukocytic
      infiltrate. The immunoprofile of the tumor showed negativity for cytokeratins and
      led to the diagnosis of a CD30-positive anaplastic large cell lymphoma.

PMID- 16983531
TI  - A novel luminescent lifetime-based optrode for the detection of gaseous and
      dissolved oxygen utilising a mixed ormosil matrix containing ruthenium (4,7
      diphenyl-1,10-phenanthroline)3Cl2 (Ru.dpp).
AB  - A novel luminescent lifetime optrode is presented for the detection of gaseous
      and dissolved oxygen. The optrode utilises ruthenium (4,7-diphenyl-1,10
      phenanthroline)(3)Cl(2) as the sensing fluorophore immobilised in a hydrophobic
      ormosil matrix. The ormosil matrix is synthesised at room temperature from
      octyltriethoxysilane and methyltriethoxysilane precursors. Investigations of
      different ormosils were conducted and the most effective one was selected for
      optrode production. Optrodes were tested for responses to gaseous and dissolved
      oxygen. Their responses were modelled using traditional two-site or two
      exponential methods and feed-forward artificial neural networks. Comparison of
      the two modelling methodologies is presented and further improvements in
      modelling and ormosil design are suggested.

PMID- 16983532
TI  - Platinum electrode coated with a bentonite-carbon composite as an environmental
      sensor for detection of lead.
AB  - A Pt wire coated with a bentonite-carbon composite in a poly(vinyl chloride)
      membrane was used for detection of lead. The sensor has a Nernstian slope of
      29.42+/-0.50 mV per decade over a wide range of concentration, 1.0 x 10(-7) to
      1.0 x 10(-3) mol L(-1) Pb(NO(3))(2). The detection limit is 5.0 x 10(-8) mol L(
      1) Pb(NO(3))(2) and the electrode is applicable in the pH range 3.0-6.7. It has a
      response time of approximately 10 s and can be used at least for three months.
      The electrode has good selectivity relative to nineteen other metal ions. The
      practical analytical utility of the electrode is demonstrated by measurement of
      Pb(II) in industrial waste and river water samples.

PMID- 16983533
TI  - Localization and replication of the systemic lupus erythematosus linkage signal
      at 4p16: interaction with 2p11, 12q24 and 19q13 in European Americans.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized
      by both population and phenotypic heterogeneity. Our group previously identified
      linkage to SLE at 4p16 in European Americans (EA). In the present study we
      replicate this linkage effect in a new cohort of 76 EA families multiplex for SLE
      by model-free linkage analysis. Using densely spaced microsatellite markers in
      the linkage region, we have localized the potential SLE susceptibility gene(s) to
      be telomeric to the marker D4S2928 by haplotype construction. In addition, marker
      D4S394 showed marginal evidence of linkage disequilibrium with the putative
      disease locus by the transmission disequilibrium test and significant evidence of
      association using a family-based association approach as implemented in the
      program ASSOC. We also performed both two-point and multipoint model-based
      analyses to characterize the genetic model of the potential SLE susceptibility
      gene(s), and the lod scores both maximized under a recessive model with
      penetrances of 0.8. Finally, we performed a genome-wide scan of the total 153 EA
      pedigrees and evaluated the possibility of interaction between linkage signals at
      4p16 and other regions in the genome. Fourteen regions on 11 chromosomes (1q24,
      1q42, 2p11, 2q32, 3p14.2, 4p16, 5p15, 7p21, 8p22, 10q22, 12p11, 12q24, 14q12,
      19q13) showed evidence of linkage, among which, signals at 2p11, 12q24 and 19q13
      also showed evidence of interaction with that at 4p16. These results provide
      important additional information about the SLE linkage effect at 4p16 and offer a
      unique approach to uncovering susceptibility loci involved in complex human
      diseases.

PMID- 16983534
TI  - The Triticum aestivum non-specific lipid transfer protein (TaLtp) gene family:
      comparative promoter activity of six TaLtp genes in transgenic rice.
AB  - Plant non-specific lipid transfer proteins (nsLTPs) are encoded by a multigene
      family and support physiological functions, which remain unclear. We adapted an
      efficient ligation-mediated polymerase chain reaction (LM-PCR) procedure that
      enabled isolation of 22 novel Triticum aestivum nsLtp (TaLtp) genes encoding
      types 1 and 2 nsLTPs. A phylogenetic tree clustered the wheat nsLTPs into ten
      subfamilies comprising 1-7 members. We also studied the activity of four type 1
      and two type 2 TaLtp gene promoters in transgenic rice using the 1-Glucuronidase
      reporter gene. The activities of the six promoters displayed both overlapping and
      distinct features in rice. In vegetative organs, these promoters were active in
      leaves and root vascular tissues while no beta-Glucuronidase (GUS) activity was
      detected in stems. In flowers, the GUS activity driven by the TaLtp7.2a,
      TaLtp9.1a, TaLtp9.2d, and TaLtp9.3e gene promoters was associated with vascular
      tissues in glumes and in the extremities of anther filaments whereas only the
      TaLtp9.4a gene promoter was active in anther epidermal cells. In developing
      grains, GUS activity and GUS immunolocalization data evidenced complex patterns
      of activity of the TaLtp7.1a, TaLtp9.2d, and TaLtp9.4a gene promoters in embryo
      scutellum and in the grain epicarp cell layer. In contrast, GUS activity driven
      by TaLtp7.2a, TaLtp9.1a, and TaLtp9.3e promoters was restricted to the vascular
      bundle of the embryo scutellum. This diversity of TaLtp gene promoter activity
      supports the hypothesis that the encoded TaLTPs possess distinct functions in
      planta.

PMID- 16983535
TI  - Photosynthetic activity of homoiochlorophyllous desiccation tolerant plant
      Haberlea rhodopensis during dehydration and rehydration.
AB  - The functional state of the photosynthetic apparatus of flowering
      homoiochlorophyllous desiccation tolerant plant Haberlea rhodopensis during
      dehydration and subsequent rehydration was investigated in order to characterize
      some of the mechanisms by which resurrection plants survive drought stress. The
      changes in the CO2 assimilation rate, chlorophyll fluorescence parameters,
      thermoluminescence, fluorescence imaging and electrophoretic characteristics of
      the chloroplast proteins were measured in control, moderately dehydrated (50%
      water content), desiccated (5% water content) and rehydrated plants. During the
      first phase of desiccation the net CO2 assimilation decline was influenced by
      stomatal closure. Further lowering of net CO2 assimilation was caused by both the
      decrease in stomatal conductance and in the photochemical activity of photosystem
      II. Severe dehydration caused inhibition of quantum yield of PSII electron
      transport, disappearance of thermoluminescence B band and mainly charge
      recombination related to S2QA- takes place. The blue and green fluorescence
      emission in desiccated leaves strongly increased. It could be suggested that
      unchanged chlorophyll content and amounts of chlorophyll-proteins, reversible
      modifications in PSII electron transport and enhanced probability for non
      radiative energy dissipation as well as increased polyphenolic synthesis during
      desiccation of Haberlea contribute to drought resistance and fast recovery after
      rehydration.

PMID- 16983536
TI  - Heterologous expression of cDNAs encoding monodehydroascorbate reductases from
      the moss, Physcomitrella patens and characterization of the expressed enzymes.
AB  - Monodehydroascorbate reductase (MDHAR; EC 1.6.5.4) catalyses the reduction of the
      monodehydroascorbate (MDHA) radical to ascorbate, using NADH or NADPH as an
      electron donor, and is believed to be involved in maintaining the reactive oxygen
      scavenging capability of plant cells. This key enzyme in the ascorbate
      glutathione cycle has been studied here in the moss Physcomitrella patens, which
      is tolerant to a range of abiotic stresses and is increasingly used as a model
      plant. In the present study, three cDNAs encoding different MDHAR isoforms of 47
      kDa were identified in P. patens, and found to exhibit enzymic characteristics
      similar to MDHARs in vascular plants despite low-sequence identity and a distant
      evolutionary relationship between the species. The three cDNAs for the P. patens
      MDHAR enzymes were expressed in Escherichia coli and the active enzymes were
      purified and characterized. Each recombinant protein displayed an absorbance
      spectrum typical of flavoenzymes and contained a single non-covalently bound FAD
      coenzyme molecule. The Km and kcat values for the heterologously expressed
      PpMDHAR enzymes ranged from 8 to 18 microM and 120-130 s(-1), respectively, using
      NADH as the electron donor. The Km values were at least an order of magnitude
      higher for NADPH. The Km values for the MDHA radical were approximately 0.5-1.0
      microM for each of the purified enzymes, and further kinetic analyses indicated
      that PpMDHARs follow a 'ping-pong' kinetic mechanism. In contrast to previously
      published data, site-directed mutagenesis indicated that the conserved cysteine
      residue is not directly involved in the reduction of MDHA.

PMID- 16983538
TI  - Decoding spike train ensembles: tracking a moving stimulus.
AB  - We consider the issue of how to read out the information from nonstationary spike
      train ensembles. Based on the theory of censored data in statistics, we propose a
      'censored' maximum-likelihood estimator (CMLE) for decoding the input in an
      unbiased way when the spike activity is observed over time windows of finite
      length. Compared with a rate-based, moment estimator, the CMLE is proved
      consistently more efficient, particularly with nonstationary inputs. Using our
      approach, we show that a dynamical input to a group of neurons can be inferred
      accurately and with high temporal resolution (50 ms) using as few as about one
      spike per neuron within each decoding window. By applying our theoretical results
      to a population coding setting, we then demonstrate that a spiking neural network
      can encode spatial information in such a way to allow fast and precise tracking
      of a moving target.

PMID- 16983539
TI  - Hemorrhagic fever with renal syndrome (HFRS, Korean hemorrhagic fever).

PMID- 16983537
TI  - Effect of LiCl on phosphoenolpyruvate carboxylase kinase and the phosphorylation
      of phosphoenolpyruvate carboxylase in leaf disks and leaves of Sorghum vulgare.
AB  - In the present work, the effect of LiCl on phosphoenolpyruvate carboxylase kinase
      (PEPCase-k), C4 phosphoenolpyruvate carboxylase (PEPCase: EC 4.1.1.31) and its
      phosphorylation process has been investigated in illuminated leaf disks and
      leaves of the C4 plant Sorghum vulgare. Although this salt induced severe damages
      to older leaves, it did not significantly alter the physiological parameters
      (photosynthesis, transpiration rate, intercellular CO2 concentration) of young
      leaves. An immunological approach was used to demonstrate that the PEPCase-k
      protein accumulated rapidly in illuminated leaf tissues, consistent with the
      increase in its catalytic activity. In vivo, LiCl was shown to strongly enhance
      the light effect on PEPCase-k protein content, this process being dependent on
      protein synthesis. In marked contrast, the salt was found to inhibit the PEPCase
      k activity in reconstituted assays and to decrease the C4 PEPCase content and
      phosphorylation state in LiCl treated plants. Short-term (15 min) LiCl treatment
      increased IP3 levels, PPCK gene expression, and PEPCase-k accumulation. Extending
      the treatment (1 h) markedly decreased IP3 and PPCK gene expression, while
      PEPCase-k activity was kept high. The cytosolic protein synthesis inhibitor
      cycloheximide (CHX), which blocked the light-dependent up-regulation of the
      kinase in control plants, was found not to be active on this process in
      preilluminated, LiCl-treated leaves. This suggested that the salt causes the
      kinase turnover to be altered, presumably by decreasing degradation of the
      corresponding polypeptide. Taken together, these results establish PEPCase-k and
      PEPCase phosphorylation as lithium targets in higher plants and that this salt
      can provide a means to investigate further the organization and functioning of
      the cascade controlling the activity of both enzymes.

PMID- 16983540
TI  - The evolution of colony-level development in the Siphonophora
      (Cnidaria:Hydrozoa).
AB  - Evolutionary developmental biology has focused almost exclusively on
      multicellular organisms, but there are other relevant levels of biological
      organization that have remained largely neglected. Animal colonies are made up of
      multiple physiologically integrated and genetically identical units called zooids
      that are each homologous to solitary, free-living animals. Siphonophores, a group
      of pelagic hydrozoans (Cnidaria), have the most complex colony-level organization
      of all animals. Here the colony-level development of five siphonophore species,
      strategically sampled across the siphonophore phylogeny, is described from
      specimens collected using deep-sea submersibles and by self-contained underwater
      breathing apparatus diving. These species include three cystonects, Bathyphysa
      sibogae, Rhizophysa filiformis, and Rhizophysa eysenhardti, and two "physonects",
      Agalma elegans and Nanomia bijuga. These data, together with previous findings,
      are analyzed in a phylogenetic framework to reconstruct key features of the
      history of colony-level organization and development in the Siphonophora. It is
      shown that gonodendra and gastrozooids of the examined cystonects arise as
      independent buds directly on the stem, whereas probud subdivision (the origin of
      feeding, reproductive, and other zooids from a single bud) is a synapomorphy of
      the Codonophora. The origin of probud subdivision is associated with the origin
      of cormidia as integrated units of colony organization, and may have allowed for
      greater morphological and ecological diversification in the Codonophora relative
      to the Cystonectae. It is also found that symmetry is labile in siphonophores,
      with multiple gains and/or losses of directional asymmetry in the group. This
      descriptive work will enable future mechanistic and molecular studies of colony
      level development in the siphonophores.

PMID- 16983541
TI  - The expression of a hunchback ortholog in the polychaete annelid Platynereis
      dumerilii suggests an ancestral role in mesoderm development and neurogenesis.
AB  - Orthologs of the Drosophila gap gene hunchback have been isolated so far only in
      protostomes. Phylogenetic analysis of recently available genomic data allowed us
      to confirm that hunchback genes are widely found in protostomes (both
      lophotrochozoans and ecdysozoans). In contrast, no unequivocal hunchback gene can
      be found in the genomes of deuterostomes and non-bilaterians. We cloned hunchback
      in the marine polychaete annelid Platynereis dumerilii and analysed its
      expression during development. In this species, hunchback displays an expression
      pattern indicative of a role in mesoderm formation and neurogenesis, and similar
      to the expression found for hunchback genes in arthropods. These data suggest
      altogether that these functions are ancestral to protostomes.

PMID- 16983542
TI  - Systematic review of pharmacotherapy of disruptive behavior disorders in children
      and adolescents.
AB  - RATIONALE: Pharmacotherapy is frequently considered in the treatment of
      disruptive behavior disorders (DBDs) in children and adolescents. There are,
      however, no systematic reviews of this literature. OBJECTIVES: The aim of this
      work is to determine whether medication is effective in treating pediatric
      disruptive behavior disorders and related problems of impulse control, as well as
      to examine differences in the treatment response and tolerability of different
      medication classes and agents. MATERIALS AND METHODS: Randomized controlled
      trials of the pharmacotherapy of DBDs in children and adolescents were reviewed,
      and a meta-analysis of 14 trials (823 participants) was conducted. RESULTS: There
      is some evidence of the effectiveness of medication in treating DBDs, with
      positive outcomes for lithium and risperidone in particular. Pharmacotherapy also
      demonstrated some efficacy in reducing symptoms of aggression. Medication was
      relatively well-tolerated, as indicated by equivalent dropout rates in medication
      and comparison groups. CONCLUSIONS: There are relatively few controlled trials of
      the pharmacotherapy of disruptive behavior disorders or other impulse control
      disorders, despite the importance of research in this area. Given the potential
      adverse effects of agents such as lithium and risperidone, a careful risk-benefit
      analysis is needed for each patient.

PMID- 16983544
TI  - Synchrony during acoustic interactions in the bushcricket Mecopoda 'Chirper'
      (Tettigoniidae:Orthoptera) is generated by a combination of chirp-by-chirp
      resetting and change in intrinsic chirp rate.
AB  - In several bushcricket species, individual males synchronise their chirps during
      acoustic interactions. Synchrony is imperfect with the chirps of one male leading
      or lagging the other by a few milliseconds. Imperfect synchrony is believed to
      have evolved in response to female preferences for leading chirps. We
      investigated the mechanism underlying synchrony in the bushcricket species
      Mecopoda 'Chirper' from Southern India using playback experiments and simulations
      of pairwise interactions. We also investigated whether intrinsic chirp period is
      a good predictor of leading probability during interactions between males. The
      mechanism underlying synchrony in this species differs from previously reported
      mechanisms in that it involves both a change in the oscillator's intrinsic rate
      and resetting on a chirp-by-chirp basis. The form of the phase response curve
      differs from those of previously reported firefly and bushcricket species
      including the closely related Malaysian species Mecopoda elongata. Simulations
      exploring oscillator properties showed that the outcome of pairwise interactions
      was independent of initial phase and alternation was not possible. Solo intrinsic
      chirp period was a relatively good predictor of leading probability. However,
      changing the intrinsic period during interactions could enable males with longer
      periods to lead during acoustic interactions.

PMID- 16983545
TI  - Extracellular long-term recordings of the isolated accessory medulla, the
      circadian pacemaker center of the cockroach Leucophaea maderae, reveal ultradian
      and hint circadian rhythms.
AB  - In the cockroach Leucophaea maderae transplantation studies located the circadian
      pacemaker center, which controls locomotor activity rhythms, to the accessory
      medulla (AMe), ventromedially to the medulla of the brain's optic lobes. The AMe
      is densely innervated via GABA- and manyfold peptide-immunoreactive neurons. They
      express ultradian action potential oscillations in the gamma frequency range and
      form phase-locked assemblies of synchronously spiking cells. Peptide application
      resulted in transient rises of extracellularly recorded activity. It remained
      unknown whether transient rises in spontaneous electrical activity as a possible
      indication of peptide release occur in the isolated circadian clock in a rhythmic
      manner. In extracellular glass electrode recordings of the isolated AMe in
      constant darkness, which lasted at least 12 h, the distribution of daytime
      dependent changes in activity independently of the absolute action potential
      frequency was examined. Rapid, transient changes in activity preferentially
      occurred at the mid-subjective night, with a minimum at the middle of the
      subjective day, hinting the presence of circadian rhythms in the isolated
      circadian clock. Additionally, ultradian rhythms in activity change that are
      multiples of a fundamental 2 h period were observed. We hypothesize that
      circadian rhythms might originate from coupled ultradian oscillations, possibly
      already at the single cell level.

PMID- 16983546
TI  - [Nasal dermoid and sinus cysts in patients with cleft malformations].
AB  - BACKGROUND: Nasal dermoid sinus cysts are uncommon congenital lesions. They are
      usually isolated occurrences and are not associated with syndromes or additional
      malformations. The coincidence of both, cleft malformations and nasal dermoid
      sinus cysts, has seldom been reported. CASE REPORTS: Within the last 2 years two
      patients with reconstructed cleft lip and palate and additional nasal dermoid
      sinus cysts underwent surgical removal. One patient with bilateral complete cleft
      lip exhibited a fistula from the medial third of the nasal dorsum up to the
      glabella. Another patient with unilateral cleft lip and Peters' plus syndrome had
      undergone removal of a nasal dermoid sinus cyst 12 years ago and was referred for
      management of recurrent disease. DISCUSSION: Concerning the common cleft
      dependent nose malformations with no midline nasal masses, there are reasons for
      the assumption that a coincidence of both anomalies might be accidental.
      Especially in Peters' plus syndrome no frequent occurrence of nasal dermoids has
      thus far been documented. However, the proximity and temporal closeness of an
      embryological pathway of the frontonasal region and lip development could also
      argue for a unique formation of both lesions. Complete surgical removal and
      plastic reconstruction simultaneously or in a second step are recommended.

PMID- 16983543
TI  - The nucleus accumbens as part of a basal ganglia action selection circuit.
AB  - BACKGROUND: The nucleus accumbens is the ventral extent of the striatum, the main
      input nucleus of the basal ganglia. Recent hypotheses propose that the accumbens
      and its dopamine projection from the midbrain contribute to appetitive behaviors
      required to obtain reward. However, the specific nature of this contribution is
      unclear. In contrast, significant advances have been made in understanding the
      role of the dorsal striatum in action selection and decision making. OBJECTIVE:
      In order to develop a hypothesis of the role of nucleus accumbens dopamine in
      action selection, the physiology and behavioral pharmacology of the nucleus
      accumbens are compared to those of the dorsal striatum. HYPOTHESES: Three
      hypotheses concerning the role of dopamine in these structures are proposed: (1)
      that dopamine release in the dorsal striatum serves to facilitate the ability to
      respond appropriately to temporally predictable stimuli (that is, stimuli that
      are so predictable that animals engage in anticipatory behavior just prior to the
      stimulus); (2) that dopamine in the nucleus accumbens facilitates the ability to
      respond to temporally unpredictable stimuli (which require interruption of
      ongoing behavior); and (3) that accumbens neurons participate in action selection
      in response to such stimuli by virtue of their direct (monosynaptic inhibitory)
      and indirect (polysynaptic excitatory) projections to basal ganglia output
      nuclei.

PMID- 16983550
TI  - Mechanism of injury influences quality of life in survivors of acute respiratory
      distress syndrome.
AB  - OBJECTIVE: Growing evidence suggests that acute respiratory distress syndrome
      (ARDS) occurring as a consequence of primary (direct) lung injury differs from
      that resulting from secondary (indirect) lung injury in terms of radiographic
      appearance, response to interventions, and outcomes. We examined whether there
      are differences in quality of life (QOL) in survivors of ARDS attributable to the
      mechanism of underlying lung injury. DESIGN AND SETTING: Prospective
      observational cohort study in 54 intensive care units in Canada and the United
      States. PATIENTS AND PARTICIPANTS: Survivors of ARDS (n=73) were grouped
      according to underlying cause of ARDS (i.e., primary vs. secondary lung injury)
      and followed prospectively for 12months. MEASUREMENTS AND RESULTS: QOL was
      assessed using the Medical Outcomes Study 36-item Short Form Health Survey (SF
      36) and the St. George's Respiratory Questionnaire (SGRQ), and spirometry was
      performed at each outpatient follow-up visit. At 3months mortality and QOL
      outcomes were similar between the groups, but by 12months patients with primary
      lung injury had significantly better QOL scores in four of eight SF-36 domains
      and in two of three domains of the SGRQ. Differences were not attributable to
      duration of ICU or hospital length of stay, duration of mechanical ventilation,
      comorbidities prior to the index illness, or differences in spirometry during the
      follow-up period. CONCLUSIONS: QOL in survivors of ARDS appears to be influenced
      by the mechanism of lung injury (primary vs. secondary), lending support to the
      concept that ARDS is a heterogeneous condition.

PMID- 16983549
TI  - Outcome in bacteremia associated with nosocomial pneumonia and the impact of
      pathogen prediction by tracheal surveillance cultures.
AB  - OBJECTIVE: To assess whether pathogen prediction in bacteremia associated with
      nosocomial pneumonia (NP) by tracheal surveillance cultures improves adequacy of
      early antibiotic therapy and impacts mortality. DESIGN AND SETTING: A
      retrospective observational study of a prospectively gathered cohort. This cohort
      included all adult patients admitted to the ICU of a tertiary care hospital from
      1992 through 2001 and who developed bacteremia associated with NP. MEASUREMENTS
      AND MAIN RESULTS: 128 episodes of bacteremia associated with NP were identified.
      In 110 episodes a tracheal surveillance culture 48-96h prior to bacteremia was
      available: this culture predicted the pathogen in 67 episodes (61%). Overall
      rates of appropriate empiric antibiotic therapy within 24 and 48h were 62 and
      87%, respectively. Pathogen prediction was associated with a significantly higher
      rate of appropriate antibiotic therapy within 24h (71 vs 45%; p=0.01), but not
      within 48h (91 vs 82%; p=0.15). Crude in-hospital mortality was 50%. Pathogen
      prediction was associated with increased survival in univariate (OR 0.43; CI 0.19
      0.93; p=0.04) and multivariate analysis (OR 0.32; CI 0.12-0.82; p=0.02).
      Multivariate analysis further identified age (OR 1.04; CI 1.01-1.07; p=0.02),
      increasing APACHEII score (OR 1.08; CI 1.02-1.15; p=0.01), and methicillin
      resistant Staphylococcus aureus (OR 5.90; CI 1.36-25.36; p=0.01) and Pseudomonas
      aeruginosa (OR 3.30; CI 1.04-10.4; p=0.04) as independent risk factors for
      mortality. CONCLUSION: Pathogen prediction in bacteremia associated with NP by
      tracheal surveillance cultures is associated with a higher rate of adequate
      empiric antibiotic therapy within 24[Symbol: see text]h and with increased
      survival.

PMID- 16983551
TI  - AFLP-based differentiation of tropical African Festuca species compared to the
      European Festuca complex.
AB  - For the first time amplified fragment length polymorphism (AFLP) fingerprinting
      is applied to classify tropical African Festuca species. Five afro-alpine narrow-
      and two afro-montane broad-leaved species from Uganda and Ethiopia are compared
      to ten European grass species. A principal coordinate analysis (PCoA) accounts
      for 62.5% with its first three coordinates. The PCoA and the neighbor-joining
      (NJ) distinguish the five narrow-leaved African Festuca species from all other
      species. The broad-leaved African Festuca africana and Festuca simensis are
      linked to the broad-leaved European species through Festuca altissima and Festuca
      gigantea, respectively. The narrow- and broad-leaved European species are
      separated as expected in the NJ. One narrow-leaved African alpine species
      recently described appears merged (i.e. Festuca richardii with Festuca
      abyssinica). We provide chromosome numbers for all seven Ugandan species and
      compare taxonomy and AFLP classification. Our most striking result is that the
      narrow-leaved African Festuca species are unique and not clustering with the
      narrow-leaved European species.

PMID- 16983552
TI  - Pairing and recombination at meiosis of Brassica rapa (AA) x Brassica napus
      (AACC) hybrids.
AB  - Interspecific crosses contribute significantly to plant evolution enabling gene
      exchanges between species. The efficiency of interspecific crosses depends on the
      similarity between the implicated genomes as high levels of genome similarity are
      required to ensure appropriate chromosome pairing and genetic recombination.
      Brassica napus (AACC) is an allopolyploid, resulting from natural hybridization
      between Brassica rapa (AA) and Brassica oleracea (CC), both being diploid species
      derived from a common ancestor. To study the relationships between genomes of
      these Brassica species, we have determined simultaneously the pairing and
      recombination pattern of A and C chromosomes during meiosis of AAC triploid
      hybrids, which result from the interspecific cross between natural B. napus and
      B. rapa. Different AAC triploid hybrids and their progenies have been analysed
      using cytogenetic, BAC-FISH, and molecular techniques. In 71% of the pollen
      mother cells, homologous A chromosomes paired regularly, and usually one
      chromosome of each pair was transmitted to the progeny. C chromosomes remained
      mainly univalent, but were involved in homoeologous pairing in 21.5% of the
      cells, and 13% of the transmitted C chromosomes were either recombined or broken.
      The rate of transmission of C chromosomes depended on the identity of the
      particular chromosome and on the way the hybrid was crossed, as the male or as
      the female parent, to B. napus or to B. rapa. Gene transfers in triploid hybrids
      are favoured between A genomes of B. rapa and B. napus, but also occur between A
      and C genomes though at lower rates.

PMID- 16983553
TI  - Tree height and age-related decline in growth in Scots pine (Pinus sylvestris
      L.).
AB  - Growth and seasonal water use was measured amongst trees growing in an old growth
      Scots pine forest in the Scottish Highlands. Three sites which differed in their
      recent management history and contained old and naturally regenerated young trees
      growing together were monitored in the field. Our results showed a clear decrease
      in growth efficiency with age, from values of around 0.25 kg m(-2) leaves year(
      1) in approximately 25-year-old trees to less than 0.1 kg m(-2) leaves year(-1)
      in trees over 200 years old. When the old trees in one of the field sites were
      released from competition by thinning, their growth efficiency reverted to that
      of coexisting young trees, indicating that the decline in growth was reversible.
      This is consistent with the results of a parallel study showing that cambial age
      had no effect on the physiology or growth of grafted seedlings originating from
      the same population studied here (Mencuccini et al. 2005). Our detailed study of
      tree water use in the field showed an overall decrease in whole-tree hydraulic
      conductance and stomatal canopy conductance with tree height in the unthinned
      stands, in agreement with the hydraulic limitation hypothesis. However, the
      effect of this reduction in hydraulic efficiency on growth was comparatively
      small, and old trees also showed consistently lower nitrogen concentrations in
      needles, suggesting that hydraulic and nutritional factors combined to produce
      the decline in growth efficiency with age observed in the studied populations.

PMID- 16983554
TI  - Early distal femoral endoprosthetic survival: cemented stems versus the Compress
      implant.
AB  - Aseptic loosening is well known following endoprosthetic replacement (EPR) using
      cemented intramedullary stems (CISs). The Compress (CPS) implant uses a novel
      spring system, achieving immediate, high compression fixation that induces bone
      hypertrophy and avoids stress shielding. We compared 26 oncologic distal femoral
      CPS patients treated at the University of California, San Francisco (UCSF, USA)
      with 26 matched CIS patients from the Royal Orthopaedic Hospital, Birmingham
      (ROH, UK). The predominant diagnosis was osteosarcoma. Each centre had only one
      device-related prosthetic failure. In the short term these results show CPS to be
      safe and effective. We await longer follow-up to assess the ongoing potential for
      prosthetic failure.

PMID- 16983555
TI  - Recurrent pyogenic cholangitis due to chronic infestation with Clonorchis
      sinensis (2006: 8b).
AB  - Recurrent pyogenic cholangitis is a common disease in Southeast Asia, where an
      association with the liver fluke Clonorchis sinensis is postulated. It is
      characterised by repeated attacks of cholangitis with multiple recurrences of
      bile duct stones and strictures. We present a case of recurrent pyogenic
      cholangitis due to chronic infestation with Clonorchis sinensis in a young Asian
      immigrant, describing its radiological appearances and also therapeutic
      strategies with a review of additional examples from the literature.

PMID- 16983556
TI  - Genetic control of plasma lipid levels in a cross derived from normoglycaemic
      Brown Norway and spontaneously diabetic Goto-Kakizaki rats.
AB  - AIMS/HYPOTHESIS: Dyslipidaemia is a main component of the insulin resistance
      syndrome. The inbred Goto-Kakizaki (GK) rat is a model of spontaneous type 2
      diabetes and insulin resistance, which has been used to identify diabetes-related
      susceptibility loci in genetic crosses. The objective of our study was to test
      the genetic control of lipid metabolism in the GK rat and investigate a possible
      relationship with known genetic loci regulating glucose homeostasis in this
      strain. MATERIALS AND METHODS: Plasma concentration of triglycerides,
      phospholipids, total cholesterol, HDL, LDL and VLDL cholesterol were determined
      in a cohort of 151 hybrids of an F2 cross derived from GK and non-diabetic Brown
      Norway (BN) rats. Data from the genome-wide scan of the F2 hybrids were used to
      test for evidence of genetic linkage to the lipid quantitative traits. RESULTS:
      We identified statistically significant quantitative trait loci (QTLs) that
      control the level of plasma phospholipids and triglycerides (chromosome 1), LDL
      cholesterol (chromosome 3) and total and HDL cholesterol (chromosomes 1 and 5).
      These QTLs do not coincide with previously identified diabetes susceptibility
      loci in a similar cross. The significance of lipid QTLs mapped to chromosomes 1
      and 5 is strongly influenced by sex. CONCLUSION/INTERPRETATION: We established
      that several genetic loci control the quantitative variations of plasma lipid
      variables in a GKxBN cross. They appear to be distinct from known GK diabetes
      QTLs, indicating that lipid metabolism and traits directly relevant to glucose
      and insulin regulation are controlled by different gene variants in this strain
      combination.

PMID- 16983557
TI  - ATP-binding cassette, subfamily G (ABCG family).
AB  - This review summarizes the characteristics of the ATP-binding cassette, subfamily
      G (ABCG family), which has five members: ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8.
      The members consist of a single ABC cassette in the amino terminal followed by
      six putative transmembrane domains, and to become functionally active, they form
      homo- or obligate heterodimers. Except for ABCG2, the members of the ABCG family
      play an important role in efflux transport of cholesterol. Mutations causing a
      loss of function of ABCG5 or ABCG8 are associated with sitosterolemia
      characterized by accumulation of phyto- and shellfish sterols. Unlike other
      members, ABCG2 is not involved in cholesterol efflux, but it exhibits broad
      substrate specificity to xenobiotic compounds. ABCG2 confers cancer cells
      resistance to anticancer drugs and plays a critical role in the pharmacokinetics
      of drugs in the clearance organs and tissue barriers. ABCG2 is also associated
      with a subpopulation phenotype of stem cells. Genetic polymorphisms of ABCG2 have
      been suggested to account for the interindividual differences in the
      pharmacokinetics of drugs.

PMID- 16983558
TI  - AICAR inhibits the Na+/H+ exchanger in rat hearts--possible contribution to
      cardioprotection.
AB  - AICAR (5-amino-1-beta-D: -ribofuranosyl-imidazole-4-carboxamide) is an adenosine
      analog which improves the recovery of the heart after ischemia. In some tissues
      AICAR enters cells and stimulates AMP-activated protein kinase (AMPK). We
      explored the mechanism of cardioprotection in isolated rat hearts. We confirmed
      that AICAR (0.5 mM) applied 10 min prior to a 30-min period of ischemia and
      present throughout ischemia and reperfusion caused a substantial improvement in
      the recovery of developed pressure on reperfusion. However, adenosine (100
      microM) produced no improvement, suggesting that the mechanism of action of AICAR
      was not increased endogenous adenosine production. Measurements of intracellular
      sodium concentration ([Na(+)](i)) showed that AICAR prevented the rapid rise of
      [Na(+)](i), which normally occurs on reperfusion. Inhibitors of the cardiac
      sodium-hydrogen exchanger (NHE1) also protect the heart from ischemic damage and
      also prevent the rapid rise of [Na(+)](i) on reperfusion, suggesting that AICAR
      might cause the inhibition of NHE1. We tested this possibility on isolated rat
      ventricular myocytes in which the recovery of pH(i) after NH(4)Cl exposure
      provides a measure of NHE1 activity. AICAR (0.5 micromM) inhibited NHE1 activity
      in response to an acid load by about 80%. To test whether the AICAR-induced
      inhibition of NHE1 arose through adenosine, we used the adenosine receptor
      blocker 8-sulfophenyltheophylline (8-SPT) and found that it had no measureable
      effect. To test whether the AICAR-induced inhibition of NHE1 might occur through
      the activation of AMPK, we measured the activity of two isoforms of AMPK.
      Surprisingly, activity was reduced, whereas in many other tissues AICAR increases
      AMPK activity. Furthermore, this effect of AMPK was blocked by 8-SPT, suggesting
      that the inhibition of AMPK arose through an adenosine-receptor-related pathway.
      We conclude that AICAR inhibits NHE1 through an unidentified pathway. This
      inhibition may make a contribution to the cardioprotective effects of AICAR.

PMID- 16983560
TI  - Sirenomelia sequence: early prenatal diagnosis of one rare case associated with
      acardiac malformation.
AB  - Sirenomelia sequence is a very rare congenital malformation, with incidence of
      around 1.5-4.2 per 100,000 births. Prenatal diagnosis of sirenomelia in the first
      trimester is rare; there are only five cases reported for the present, and the
      association of sirenomelia with acardiac malformation is even rarer. We present a
      rare case of sirenomelia associated with acardiac malformation detected in the
      first trimester through combined two-dimensional, three-dimensional and color
      Doppler sonographies.

PMID- 16983561
TI  - Prenatal exclusion of subtelomeric deletion 1p by fluorescent in situ
      hybridization.
AB  - BACKGROUND: Subtelomeric deletion 1p is difficult to detect from banded
      karyotypes. Recent developments in the field of molecular cytogenetics have made
      it possible for submicroscopic rearrangements within chromosomes to be detected
      using fluorescence in situ hybridization (FISH) techniques. MATERIALS AND
      METHODS: We describe prenatal FISH testing of subtelomeric 1p deletion in a fetus
      of a mother whose previous child had subtelomeric 1p deletion. RESULTS:
      Fluorescent in situ hybridization from fetal cells demonstrated normal 1p, thus
      predicting a very high likelihood of an unaffected fetus. The study was confirmed
      by the birth of a normal neonate. CONCLUSIONS: We report the use of molecular
      genetic testing to exclude subtelomeric 1p deletion prenatally. Prenatal
      diagnostic testing for a known deletion is a reasonable option for couples at
      risk for having a child with subtelomeric 1p deletion. Molecular testing is more
      accurate and reliable than ultrasonography and provides families with
      reassurance.

PMID- 16983559
TI  - Biological treatment strategies for disc degeneration: potentials and
      shortcomings.
AB  - Recent advances in molecular biology, cell biology and material sciences have
      opened a new emerging field of techniques for the treatment of musculoskeletal
      disorders. These new treatment modalities aim for biological repair of the
      affected tissues by introducing cell-based tissue replacements, genetic
      modifications of resident cells or a combination thereof. So far, these
      techniques have been successfully applied to various tissues such as bone and
      cartilage. However, application of these treatment modalities to cure
      intervertebral disc degeneration is in its very early stages and mostly limited
      to experimental studies in vitro or in animal studies. We will discuss the
      potential and possible shortcomings of current approaches to biologically cure
      disc degeneration by gene therapy or tissue engineering. Despite the increasing
      number of studies examining the therapeutic potential of biological treatment
      strategies, a practicable solution to routinely cure disc degeneration might not
      be available in the near future. However, knowledge gained from these attempts
      might be applied in a foreseeable future to cure the low back pain that often
      accompanies disc degeneration and therefore be beneficial for the patient.

PMID- 16983562
TI  - Evaluation of factors that may be responsible for cyclic change of CA125 levels
      during menstrual cycle.
AB  - OBJECTIVE: To evaluate the factors responsible for fluctuation of CA125 levels
      during menstrual cycle METHODS: The study was performed with patients who had
      undergone hysterectomy for benign gynecological disease (group I, n = 30) and
      patients who had undergone laparoscopy for tubal ligation (group II, n = 30) or
      for investigation of pelvic cause of infertility (group III, n = 24) and showed
      normal laparoscopic findings. In groups II and III, blood samplings for serum
      CA125 determination were performed in menstrual and no-menstrual period. In group
      I, sampling times were determined by using estrogen and progesterone levels. Mean
      serum CA125 concentrations were compared using one-way analysis of variance
      (ANOVA) for multiple group comparisons and paired t test for within-group
      comparisons. RESULTS: Intra-individual serum CA125 concentrations of group I was
      not significantly different (P > 0.05). In group II, mean menstrual CA125
      concentration was on average 18.2% higher than that of non-menstrual
      concentration (P < 0.001). Group III showed a similar pattern to that of group
      II, with a difference of 22% (P < 0.001). Mean CA125 concentration of group I in
      both menstrual and non-menstrual period was lower than those of groups II and III
      (P < 0.001). However, there was no significant difference between groups II and
      III when compared with the corresponding menstrual and non-menstrual CA125
      concentrations (P > 0.05). CONCLUSION: Endometrium is responsible for the cyclic
      changes in serum CA125 concentration during menstrual cycle.

PMID- 16983563
TI  - Dexpanthenol attenuates lipid peroxidation and testicular damage at experimental
      ischemia and reperfusion injury.
AB  - Prevention of tissue damage after testicular torsion caused by I/R injury is
      still a clinical and experimental problem. There are many experimental studies
      made with several chemicals in the literature for decreasing the effect of
      reactive oxygen species after ischemia and reperfusion. Dexpanthenol (Dxp) is the
      biologically active alcohol of pantothenic acid. Pantothenic acid increases the
      content of reduced glutathione, Coenzyme A and ATP in cell. We studied the effect
      of Dxp on lipid peroxidation and testicular damage. Forty adult rats were
      separated randomly into five groups: group Sh, Sham-operation; group TD, torsion
      detorsion; group NS, torsion-normal saline-detorsion; group D, torsion-Dxp 250
      mg/kg detorsion; group D2, torsion-Dxp 500 mg/kg detorsion group. Serum MDA
      levels were taken before detorsion, after torsion at the first and fifth minute
      and at the first hour. Tissue sample was taken at the first hour. The alterations
      of I/R injury on testis were histological graded. Serum MDA levels were
      significantly lower in group D2 compared to all groups. The histopathology score
      of group D2 was significantly lower than groups TD, NS and D. Histopathological
      score and serum MDA levels are strikingly compatible. Dxp attenuated lipid
      peroxidation and tissue damage at I/R injury. This effect depends on its
      antioxidant effect with increasingly reduced glutathione, Coenzyme A and ATP. The
      effect of Dxp on I/R injury has been shown for the first time in the experimental
      testicular torsion.

PMID- 16983564
TI  - Bilateral discoid medial menisci accompanied by distal arthrogryposis: a case
      report.
AB  - Discoid meniscus shows a propensity for the lateral side, and bilateral discoid
      medial meniscus is extremely rare. The present patient had a history of windblown
      hand and clubfoot, and bilateral discoid medial meniscus was associated with
      distal arthrogryposis. There has been no previous case report about the
      coexistence of meniscal abnormalities and distal arthrogryposis. While the
      association between distal arthrogryposis and meniscal abnormalities is unknown,
      it is interesting that discoid medial meniscus (a rare meniscus abnormality)
      occurred in the presence of arthrogryposis. We performed bilateral arthroscopic
      partial meniscectomy (reshaping) to treat discoid meniscus in this case, and the
      patient used outer wedge arch supports postoperatively. Neither relapse of
      meniscal symptoms nor arthrosis has occurred postoperatively in this patient, but
      long-term follow-up is considered to be necessary.

PMID- 16983565
TI  - Trochlear osteotomy for patellar instability: satisfactory minimum 2-year results
      in patients with dysplasia of the trochlea.
AB  - Trochlear dysplasia is a predisposing factor for recurrent patellar instability.
      We evaluated the results of an anterior lateral femoral condyle open wedge
      osteotomy for treating patellar instability. A total of 16 consecutive patients
      (19 knees) with symptoms of recurrent patellar instability and trochlear
      dysplasia identified using a true lateral radiograph of the knee underwent an
      anterior lateral femoral osteotomy. Outcomes were documented at 2 years minimum
      follow-up using the Lysholm scale, the patellofemoral score, WOMAC score and
      standard conventional radiographs. In 17 knees, patients reported good
      improvement in stability (no dislocations) and most patients had a marked
      improvement in pain and functional scores at follow-up (mean follow-up 51
      months). No serious complications occurred. Anterior femoral osteotomy of the
      lateral condyle appears to be a satisfactory and safe method for treating
      patients with patellofemoral joint instability caused by trochlea dysplasia. In
      selected cases this procedure can be used to correct trochlea dysplasia. In our
      opinion, the key to a successful treatment of patellofemoral instability is to
      successfully distinguish the anatomic deficiencies and to correct the anatomical
      abnormality.

PMID- 16983567
TI  - Morphological and molecular comparison of white truffle ectomycorrhizae.
AB  - In the present study, white truffle ectomycorrhizae (EM) collected in deciduous
      forests (Populus, Quercus, and Fagus) from Hungary were characterized by
      morphological-anatomical and molecular methods. Our investigations suggest that
      the EM of white truffles (e.g., Tuber rapaeodorum, Tuber puberulum, Tuber rufum)
      are common and abundant members of the forest communities in the area. The ITS
      sequences of 14 EM specimens and 46 additional fruitbody sequences from the
      GenBank were clustered into four main groups in phylogenetic analyses. In the ITS
      1 region, a characteristic indel pattern was found, which supports the clades.
      Although our analyses indicate definite genetic distance between the groups of
      the phylogenetic tree, these clades do not correspond to the traditional taxons
      identified by fruitbody characteristics. Comparison of the ectomycorrhizae shows
      that neither is mycorrhizal anatomy a good tool to separate the groups, because
      the characters (like the epidermoid or angular mantle structure, cell wall
      thickness, the sape and size of cystidia) are too variable and overlap between
      the clades. The interspecific similarity, observed both in ectomycorrhizal and
      fruitbody characters, strengthen the sensu lato morpho-species concept of this
      group. Our study, which combines comprehensive molecular and anatomical approach
      to characterize and identify ectomycorrhizae of white truffles from natural
      samples, stress out the need of the taxonomical revision of this group.

PMID- 16983566
TI  - Effect of pH and human serum albumin on the cytotoxicity of a glucuronide prodrug
      of 9-aminocamptothecin.
AB  - PURPOSE: 9-aminocamptothecin glucuronide (9ACG) is a prodrug of 9
      aminocamptothecin (9AC) that displays potent antitumor activity against human
      tumor xenografts in nude mice. Camptothecins exist in a pH dependent equilibrium
      between active lactone and inactive carboxy forms that can be altered by binding
      to human serum albumin (HSA). Here we investigated the influence of pH and HSA on
      the lactone-carboxy equilibrium, HSA binding, and cytotoxicity of 9ACG. METHODS:
      Microfiltration and HPLC were used to measure the influence of pH on lactone to
      carboxy conversion and HSA binding of 9ACG as compared to other camptothecins. In
      vitro cytotoxicity of drugs was determined against EJ human bladder carcinoma
      cells and CL1-5 human lung cancer cells. RESULTS: The rate of lactone to carboxy
      conversion was similar for 9ACG and 9AC. Decreasing the pH from 7.6 to 6.0
      increased the equilibrium levels of the lactone forms of the drugs from 20 to
      almost 95% of total drug. HSA moderately diminished the amount of free 9ACG
      lactone but did not change the ratio of 9ACG lactone to 9ACG carboxy. Consistent
      with the effect of pH on lactone levels, lowering the pH of EJ human bladder
      carcinoma cells from 7.6 to 6.8 decreased the IC(50) of 9ACG from 480 to 98 nM
      and 9AC from 33 to 12 nM. Activation of 9ACG by human beta-glucuronidase anchored
      on the surface of EJ cells further decreased its IC(50) value to 26 nM. Although
      HSA significantly decreased the cytotoxicity of 9AC and 9ACG, activation of 9ACG
      at cancer cells with an antibody-beta-glucuronidase immunoconjugate produced
      greater cytotoxicity than 9AC. CONCLUSIONS: Acidification and targeted delivery
      of beta-glucuronidase can enhance 9ACG cytotoxicity even in the presence of HSA.

PMID- 16983568
TI  - Mycorrhization helper bacteria: a case of specificity for altering ectomycorrhiza
      architecture but not ectomycorrhiza formation.
AB  - Mycorrhization helper bacteria (MHB), isolated from phylogenetically distinct
      ectomycorrhizal symbioses involving Lactarius rufus, Laccaria bicolor or Suillus
      luteus, were tested for fungus specificity to enhance L. rufus-Pinus sylvestris
      or L. bicolor-P. sylvestris mycorrhiza formation. As MHB isolated from the L.
      rufus and S. luteus mycorrhiza were originally characterised using a microcosm
      system, we assessed their ability to enhance mycorrhiza formation in a glasshouse
      system in order to determine the extent to which MHB are system-specific.
      Paenibacillus sp. EJP73, an MHB for L. rufus in the microcosm, significantly
      enhanced L. bicolor mycorrhiza formation in the glasshouse, demonstrating that
      the MHB effect of this bacterium is neither fungus-specific nor limited to the
      original experimental system. Although the five MHB strains studied were unable
      to significantly enhance L. rufus mycorrhiza formation, two of them did have a
      significant effect on dichotomous short root branching by L. rufus. The effect
      was specific to Paenibacillus sp. EJP73 and Burkholderia sp. EJP67, the two
      strains isolated from L. rufus mycorrhiza, and was not associated with auxin
      production. Altered mycorrhiza architecture rather than absolute number of
      mycorrhizal roots may be an important previously overlooked parameter for
      defining MHB effects.

PMID- 16983569
TI  - Rationalizing molecular analysis of field-collected roots for assessing diversity
      of arbuscular mycorrhizal fungi: to pool, or not to pool, that is the question.
AB  - For rationalizing molecular analysis of field-collected roots in diversity
      studies on arbuscular mycorrhiza, we compared three different approaches. After
      DNA extraction from 50 root samples of Plantago lanceolata grown on monoculture
      plots at a former arable field site, (1) DNAs were amplified separately by nested
      PCR and each amplicon was cloned separately; (2) DNAs were amplified separately
      by nested PCR, 1 mul of each amplicon was pooled, and a single cloning was made
      from the resulting amplicons mix; and (3) DNAs were pooled and the single
      amplicon derived from the nested PCR was cloned. Based on these three different
      methods, 109 nuclear ribosomal internal transcribed spacer sequences were
      obtained. Methods 1 and 2 enabled the detection of almost similar levels of
      arbuscular mycorrhizal fungal diversity. However, method 1 was expensive and time
      consuming as much more cloning had to be done. Method 3 was completely biased by
      preferential amplification of nontarget organisms, which were only detected in
      low frequencies by the other methods.

PMID- 16983570
TI  - Proton magnetic resonance spectroscopy in childhood brainstem lesions.
AB  - BACKGROUND: Diagnosis of brainstem lesions in children based on magnetic
      resonance imaging alone is a challenging problem. Magnetic resonance spectroscopy
      (MRS) is a noninvasive technique for spatial characterization of biochemical
      markers in tissues and gives information regarding cell membrane proliferation,
      neuronal damage, and energy metabolism. METHODS: We measured the concentrations
      of biochemical markers in five children with brainstem lesions and evaluated
      their potential diagnostic significance. Images and spectra were acquired on a
      1.5-T imager. The concentrations of N-acetylaspartate, tetramethylamines (e.g.,
      choline), creatine, phosphocreatine, lactate, and lipids were measured within
      lesions located at the brainstem using Point-resolved spectroscopy sequences.
      RESULTS: Diagnosis based on localized proton spectroscopy included brainstem
      glioma, brainstem encephalitis, demyelination, dysmyelination secondary to
      neurofibromatosis type 1 (NF 1), and possible infection or radiation necrosis. In
      all but one patient, diagnosis was confirmed by biopsy or by clinical follow-up.
      CONCLUSIONS: This small sample of patients suggests that MRS is important in the
      differential diagnosis between proliferative and nonproliferative lesions in
      patients without neurofibromatosis. Unfortunately, in cases of NF 1, MRS can have
      a rather misdiagnosis role.

PMID- 16983571
TI  - Clinical impact of CCM mutation detection in familial cavernous angioma.
AB  - INTRODUCTION AND BACKGROUND: A 3-year-old Bosnian girl with a large symptomatic
      brainstem and multiple supratentorial cavernous angiomas, who underwent
      neurosurgical treatment, is presented. As multiple cavernomas are more common in
      familial cases, genetic analyses and neuroradiological imaging were performed in
      the patient and her parents to see whether there was any evidence for
      inheritance. This information is important for genetic counseling and provision
      of medical care for at-risk relatives. Currently, no recommendation is available
      on how to manage these cases. RESULTS: Genetic analyses demonstrated a novel CCM1
      frameshift mutation (c.1683_1684insA; p.V562SfsX6) in the child and the
      asymptomatic 27-year-old mother. Sensitive gradient-echo magnetic resonance
      imaging of the mother revealed multiple supratentorial lesions, whereas analogous
      imaging of the father showed no pathological findings. CONCLUSION: This case
      exemplifies that seemingly sporadic cases with multiple lesions might well be
      hereditary and that presymptomatic genetic testing of family members may identify
      relatives for whom clinical and neuroradiological monitoring is indicated.

PMID- 16983572
TI  - Giant prolactinomas in adolescence: an uncommon cause of blindness.
AB  - INTRODUCTION: Prolactinomas in childhood and adolescence are rare. However, in
      male patients in particular they may become extremely large and invasive,
      resulting in visual impairment without necessarily producing endocrine symptoms.
      CASE REPORTS: We report on two adolescent males who presented with deteriorating
      vision over a long period of time and who had optic atrophy on examination.
      Magnetic resonance imaging identified tumours with extensive anterior skull base
      invasion and suprasellar extension. Prolactin levels in both patients were
      markedly elevated, and a diagnosis of prolactinoma was made. Bromocriptine
      treatment was started resulting in lowered prolactin levels, improved vision and
      tumour shrinkage on imaging. CONCLUSION: A male child or adolescent presenting
      with diminished vision and found to have suprasellar or anterior skull base
      tumour should have their prolactin levels checked to rule out a prolactinoma,
      which can be successfully managed with medical therapy.

PMID- 16983573
TI  - Genome-wide microRNA profiling in human fetal nervous tissues by oligonucleotide
      microarray.
AB  - OBJECTS: Our objective was to develop an oligonucleotide DNA microarray (OMA) for
      genome-wide microRNA profiling and use this method to find miRNAs, which control
      organic development especially for nervous system. MATERIALS AND METHODS:
      Eighteen organic samples included cerebrum and spinal cord samples from two
      aborted human fetuses. One was 12 gestational weeks old (G12w) and the other was
      24 gestational weeks old (G24w). Global miRNA expression patterns of different
      organs were investigated using OMA and Northern blot. CONCLUSION: The OMA
      revealed that 72-83% of miRNAs were expressed in human fetal organs. A series of
      microRNAs were found specifically and higher-expressed in the human fetal nervous
      system and confirmed consistently by Northern blot, which may play a critical
      role in nervous system development.

PMID- 16983574
TI  - Leptomeninges as a site of relapse in locally controlled, diffuse pontine glioma
      with review of literature.
AB  - CASE REPORT: Leptomeningeal involvement in diffuse intrinsic brain stem gliomas
      is rarely diagnosed clinically and in majority of the instances diagnosed only on
      postmortem examination. We report two cases of diffuse pontine glioma diagnosed
      clinicoradiologically and treated with conventional radiotherapy. OBSERVATIONS:
      On follow-up, both patients showed clinical features suggestive of meningeal
      spread although imaging for pontine tumor showed stable disease. Leptomeningeal
      disease in the spine was confirmed on imaging and in one case by cerebrospinal
      fluid examination also. During the follow-up of patients with pontine glioma, the
      possibility of leptomeningeal involvement must be borne in mind.

PMID- 16983575
TI  - The use of vacuum assisted closure (VAC) in soft tissue injuries after high
      energy pelvic trauma.
AB  - BACKGROUND: Application of vacuum-assisted closure (VAC) in soft tissue defects
      after high-energy pelvic trauma is described as a retrospective study in a level
      one trauma center. MATERIALS AND METHODS: Between 2002 and 2004, 13 patients were
      treated for severe soft tissue injuries in the pelvic region. All musculoskeletal
      injuries were treated with multiple irrigation and debridement procedures and
      broad-spectrum antibiotics. VAC was applied as a temporary coverage for defects
      and wound conditioning. RESULTS: The injuries included three patients with
      traumatic hemipelvectomies. Seven patients had pelvic ring fractures with five
      Morel-Lavallee lesions and two open pelviperineal trauma. One patient suffered
      from an open iliac crest fracture and a Morel-Lavallee lesion. Two patients
      sustained near complete pertrochanteric amputations of the lower limb. The
      average injury severity score was 34.1 +/- 1.4. The application of VAC started in
      average 3.8 +/- 0.4 days after trauma and was used for 15.5 +/- 1.8 days. The
      dressing changes were performed in average every 3 days. One patient (8%) with a
      traumatic hemipelvectomy died in the course of treatment due to septic
      complications. CONCLUSION: High-energy trauma causing severe soft tissues
      injuries requires multiple operative debridements to prevent high morbidity and
      mortality rates. The application of VAC as temporary coverage of large tissue
      defects in pelvic regions supports wound conditioning and facilitates the
      definitive wound closure.

PMID- 16983576
TI  - Liver resective surgery: a multivariate analysis of postoperative outcome and
      complication.
AB  - INTRODUCTION: Notwithstanding technical advances and high experience of liver
      resection of specialized centers, the rate of complications after surgical
      resection could be high. In this study, we analyzed causes and foreseeable risk
      factors linked to postoperative morbidity on the ground of data derived from a
      single center surgical population. MATERIALS AND METHODS: From September 1989 to
      March 2005, 134 consecutive patients had liver resection for Hcc and 153
      consecutive patients with liver metastasis (derived from either colorectal cancer
      or noncolorectal cancer) at our department. We performed 22 major hepatectomy, 20
      left hepatectomy, 14 trisegmentectomy, 77 bisegmentectomy and/or left lobectomy,
      74 segmentectomy, and 80 wedge resection. RESULTS: In-hospital mortality rate was
      4.5%, about 7% in Hcc cases and 2.6% in liver metastasis. Morbidity rate was
      47.7%, caused by the rising of ascites (10%), temporary impairment liver function
      (19%), biliary fistula (6%), hepatic abscess (25%), hemoperitoneum (10%), and
      pleural effusion (30%) sometimes combined each other. Some variables, associated
      with the technical aspects of surgical procedure, are responsible of the rising
      of complication as: Pringle maneuver length of more than 20 minutes (p=0.001);
      the type of liver resection procedure [major hepatectomy (p=0.02), left
      hepatectomy (p=0.04), trisegmentectomy (p=0.04), bisegmentectomy and/or left
      lobectomy (p=0.04)]; and the request of an amount of blood transfusion of more
      than 600 cc (p=0.04). Also, both liver dysfunction, in particular Child A vs B
      and C (p=0.01), and histopathological grading (p=0.01) are associated with a high
      rate of postsurgical complication in Hcc cases. CONCLUSION: We make the following
      recommendations: every liver resection should be planned after intraoperative
      ultrasonography, anatomical surgical procedure should be preferred instead of
      wedge resection, and modern devices should be used, like Argon Beam and Ligasure
      dissector, to reduce the incidence of both intraoperative and postoperative
      bleeding and biliary leakage.

PMID- 16983577
TI  - Metastases to the thyroid gland: seventeen cases operated on in a single clinical
      center.
AB  - BACKGROUND AND AIMS: In spite of its rich vasculature, the thyroid gland is
      rarely the site of metastatic disease. The incidence of such metastases differs
      depending on the type of the analyzed material. In clinical papers, the incidence
      is low and, according to various sources, amounts to 2-3% of all malignant tumors
      of the thyroid. Most commonly, the primary tumor is located in the breast,
      bronchi, gastrointestinal system, (the colon, esophagus, or stomach) and kidneys.
      Usually, metastatic thyroid disease is identified upon autopsy, and only sporadic
      cases are encountered in clinical material. The authors present their experience
      in treating metastatic disease involving the thyroid gland based on the analysis
      of their clinical material consisting of patients operated on in a single center.
      MATERIALS AND METHODS: Seventeen patients presented with metastatic tumors of the
      thyroid. The material was further analyzed retrospectively. The group included
      four men and 13 women, with the male to female ratio of 1:4.25. The age of the
      patients ranged from 46 to 76 years, with the mean age amounting to 62+/-9.78
      years. Eleven patients were diagnosed based on fine needle aspiration biopsy
      (FNAB). RESULTS: In 13 patients, the primary lesion was a clear cell carcinoma of
      the kidney, in one breast cancer, in another one uterine carcinoma. In two
      patients, no primary focus location was established. All the patients were
      treated surgically. Twelve patients were consistently followed up after the
      surgery. Of this group, seven are still alive, including five individuals with
      metastases of renal carcinomas, but without recurrent disease. Five patients died
      due to disseminated neoplastic disease. No data are available on three patients.
      The mean follow-up time after thyroid surgery was 3.9 years. The longest followed
      up survival time was 11 years. CONCLUSIONS: The most commonly clinically detected
      and treated surgically metastatic lesion of the thyroid gland is clear cell
      cancer of the kidney. In cases of renal cancer metastases to the thyroid gland, a
      total thyroidectomy seems to be warranted, although it does not affect the
      survival time.

PMID- 16983578
TI  - Geomagnetic field modulates artificial static magnetic field effect on arterial
      baroreflex and on microcirculation.
AB  - Spreading evidence suggests that geomagnetic field (GMF) modulates artificial
      magnetic fields biological effect and associated with increased cardiovascular
      morbidity. To explore the underlying physiological mechanism we studied 350 mT
      static magnetic field (SMF) effect on arterial baroreflex-mediated skin
      microcirculatory response in conjunction with actual geomagnetic activity,
      reflected by K and K ( p ) indices. Fourteen experiments were performed in
      rabbits sedated by pentobarbital infusion (5 mg/kg/h). Mean femoral artery blood
      pressure, heart rate, and the ear lobe skin microcirculatory blood flow, measured
      by microphotoelectric plethysmogram (MPPG), were simultaneously recorded before
      and after 40 min of NdFeB magnets local exposure to sinocarotid baroreceptors.
      Arterial baroreflex sensitivity (BRS) was estimated from heart rate/blood
      pressure response to intravenous bolus injections of nitroprusside and
      phenylephrine. We found a significant positive correlation between SMF-induced
      increase in BRS and increment in microvascular blood flow (DeltaBRS with
      DeltaMPPG, r=0.7, p<0.009) indicated the participation of the arterial baroreflex
      in the regulation of the microcirculation and its enhancement after SMF exposure.
      Geomagnetic disturbance, as opposed to SMF, decreased both microcirculation and
      BRS, and counteracted SMF-induced increment in microcirculatory blood flow (K
      index with DeltaMPPG; r (s)=-0.55, p<0.041). GMF probably affected central
      baroreflex pathways, diminishing SMF direct stimulatory effect on sinocarotid
      baroreceptors and on baroreflex-mediated vasodilatatory response. The results
      herein may thus point to arterial baroreflex as a possible physiological
      mechanism for magnetic-field cardiovascular effect. It seems that geomagnetic
      disturbance modifies artificial magnetic fields biological effect and should be
      taken into consideration in the assessment of the final effect.

PMID- 16983580
TI  - Working memory components and imagery instructions in the elaboration of a
      spatial mental model.
AB  - The paper investigates the involvement of verbal and visuo-spatial working memory
      during the processing of spatial texts via a dual-task paradigm. Subjects were
      presented with three texts describing locations from a route perspective, and had
      either to imagine themselves moving along a route in surroundings or to rehearse
      verbal information. Concurrently they had to perform a spatial tapping task, an
      articulatory task, or no secondary task. Performance on a verification test used
      to assess the product of comprehension showed that the concurrent tapping task
      impaired performance in the imagery instructions group but not in the repetition
      instructions group, and caused the beneficial effect of imagery instructions to
      vanish. This result was not observed with the articulatory task, where
      interference effects were similar in both instructions groups. Performance on the
      concurrent tasks confirmed the pattern obtained with the verification test. In
      addition, results seem partly dependent on the capacity of spatial working memory
      as measured by the Corsi Blocks Test. We argue that these results clarify the
      processes of the construction of a spatial mental model, and confirm that the
      visuo-spatial working memory is involved in mental imagery.

PMID- 16983581
TI  - The role of visuo-spatial working memory in map learning: new findings from a map
      drawing paradigm.
AB  - Recently, increasing attention has been devoted to the study of the role of visuo
      spatial working memory (VSWM) in environmental learning and spatial navigation.
      The present research was aimed at investigating the role of VSWM in map learning
      using a map drawing paradigm. In the first study, a dual task methodology was
      used. Results showed that map drawing was selectively impaired by a spatial
      tapping task that was executed during the map learning phase, hence supporting
      the hypothesis that VSWM plays an essential role in learning from maps. In the
      second study, using a correlational methodology, it was shown that performance in
      simultaneous VSWM tasks, but not in sequential VSWM tasks, predicted map drawing
      skills. These skills "in turn" correlated with map learning abilities. Finally,
      in the third study, we replicated the results of the second study, by using a
      different map. To our knowledge, the present study is the first to find evidence
      that the simultaneous aspects of VSWM play a fundamental role in learning from
      maps.

PMID- 16983582
TI  - Wayfinding with words: spatial learning and navigation using dynamically updated
      verbal descriptions.
AB  - This work investigates whether large-scale indoor layouts can be learned and
      navigated non-visually, using verbal descriptions of layout geometry that are
      updated, e.g. contingent on a participant's location in a building. In previous
      research, verbal information has been used to facilitate route following, not to
      support free exploration and wayfinding. Our results with blindfolded-sighted
      participants demonstrate that accurate learning and wayfinding performance is
      possible using verbal descriptions and that it is sufficient to describe only
      local geometric detail. In addition, no differences in learning or navigation
      performance were observed between the verbal study and a control study using
      visual input. Verbal learning was also compared to the performance of a random
      walk model, demonstrating that human search behavior is not based on chance
      decision-making. However, the model performed more like human participants after
      adding a constraint that biased it against reversing direction.

PMID- 16983583
TI  - Using geometry to specify location: implications for spatial coding in children
      and nonhuman animals.
AB  - The study of spatial cognition has benefited greatly from a technique known as
      the disorientation procedure. This procedure was originally used with rats to
      show that they relied on the geometry of an enclosed space to locate a target
      hidden in that space. Disorientation has since been used with a variety of mobile
      animals, including human children, to examine the coding of geometric
      information. Here, we focus mostly on our recent work with young children. We
      examine a set of issues concerning reorientation--namely, the nature of geometric
      coding, the processes invoked by disorientation, and the developmental origins of
      using geometric information to determine location. We have employed a variety of
      methods to examine these issues; the methods include analyzing search behaviors,
      using spaces of different shapes, varying viewing position, and comparing
      different disorientation procedures. The implications for how children and
      nonhuman animals code geometric information are discussed.

PMID- 16983584
TI  - Soft tissue removal by maceration and feeding of Dermestes sp.: impact on
      morphological and biomolecular analyses of dental tissues in forensic medicine.
AB  - Maceration techniques remove soft tissue by the destruction of biomolecules, but
      the applied techniques may also affect the morphology and the molecular integrity
      of the hard tissue itself. The impact of seven different techniques for soft
      tissue removal on morphological and biomolecular parameters of teeth and dental
      tissues was systematically examined. All methods tested showed significant
      changes in dental morphology and in the molecular integrity of DNA and the dental
      proteins, as revealed by aspartic acid racemisation (AAR). In forensic casework
      this may have severe impacts on the results of morphological methods (e.g. age
      estimation based on root translucency) and of biomolecular analyses (e.g. age
      estimation based on AAR and DNA analysis). Therefore, age estimation based on AAR
      should not be applied to tissue treated in such a manner, and it is recommended
      that teeth for analysis should be extracted before soft tissue removal. DNA in
      the hard tissue seems to be less susceptible to soft tissue removal than
      proteins, and several of the tested maceration techniques appear not to have a
      damaging effect on DNA. Generally, the indication for soft tissue removal demands
      a careful case management to avoid methodological collisions.

PMID- 16983585
TI  - Spatial & temporal variations of PM10 and particle number concentrations in urban
      air.
AB  - The size of particles in urban air varies over four orders of magnitude (from
      0.001 microm to 10 microm in diameter). In many cities only particle mass
      concentrations (PM10, i.e. particles <10 microm diameter) is measured. In this
      paper we analyze how differences in emissions, background concentrations and
      meteorology affect the temporal and spatial distribution of PM10 and total
      particle number concentrations (PNC) based on measurements and dispersion
      modeling in Stockholm, Sweden. PNC at densely trafficked kerbside locations are
      dominated by ultrafine particles (<0.1 microm diameter) due to vehicle exhaust
      emissions as verified by high correlation with NOx. But PNC contribute only
      marginally to PM10, due to the small size of exhaust particles. Instead wear of
      the road surface is an important factor for the highest PM10 concentrations
      observed. In Stockholm, road wear increases drastically due to the use of studded
      tires and traction sand on streets during winter; up to 90% of the locally
      emitted PM10 may be due to road abrasion. PM10 emissions and concentrations, but
      not PNC, at kerbside are controlled by road moisture. Annual mean urban
      background PM10 levels are relatively uniformly distributed over the city, due to
      the importance of long range transport. For PNC local sources often dominate the
      concentrations resulting in large temporal and spatial gradients in the
      concentrations. Despite these differences in the origin of PM10 and PNC, the
      spatial gradients of annual mean concentrations due to local sources are of equal
      magnitude due to the common source, namely traffic. Thus, people in different
      areas experiencing a factor of 2 different annual PM10 exposure due to local
      sources will also experience a factor of 2 different exposure in terms of PNC.
      This implies that health impact studies based solely on spatial differences in
      annual exposure to PM10 may not separate differences in health effects due to
      ultrafine and coarse particles. On the other hand, health effect assessments
      based on time series exposure analysis of PM10 and PNC, should be able to observe
      differences in health effects of ultrafine particles versus coarse particles.

PMID- 16983586
TI  - Neonatal pain analyzer: development and validation.
AB  - We developed a pain analyzer (ABC analyzer) to perform automatic acoustic
      analysis of neonatal crying and to provide an objective estimate of neonatal
      pain. The ABC analyzer uses a validated pain scale (ABC scale) based on three
      acoustic parameters: pitch frequency, normalized RMS amplitude, and presence of a
      characteristic frequency- and amplitude-modulated crying feature, defined as
      "siren cry". Here we assessed the reliability of the analyzer. We enrolled 57
      healthy neonates. Each baby was recorded with a video camera during heel prick.
      Pain intensity was evaluated using a validated scale [Douleur Aigue du Nouveau-Ne
      (DAN) scale] and the analyzer and the two scores were compared. We found a
      statistically significant concordance between the DAN score and ABC analyzer
      score (p < 0.0001). The ABC analyser is a novel approach to cry analysis that
      should now have its properties carefully evaluated in a series of studies, just
      as is necessary in the development of any other pain measurement tool.

PMID- 16983587
TI  - Tamoxifen therapy conveys increased risk of developing a macular hole.
AB  - PURPOSE: To determine etiological factors in the development of, as well as
      anatomic success rate and visual outcome of a large consecutive series of macular
      hole surgeries. METHODS: Retrospective analysis of 300 consecutive cases of
      macular hole surgery by a single surgeon (RDB) between 1999 and 2003. Patients'
      medical and surgical histories were recorded and analysed for factors involved in
      aetiology and visual outcome. RESULTS: There were 8 (4.12%) women, on tamoxifen
      in the study, two of these women had bilateral macular holes. When this study
      prevalence of tamoxifen therapy (4.12%) was compared to the estimated percentage
      of women in the same age group in the Australian population on tamoxifen (0.82%),
      a statistically significant difference (p value 0.0001) was found. Analysis of
      the number of bilateral holes in the tamoxifen group compared to the non
      tamoxifen group was suggestive of an increased incidence of bilateral holes but
      not to a significantly significant degree. CONCLUSION: Whilst no published
      reports link tamoxifen and macular holes, this may be due to the low incidence of
      the condition. Our study demonstrates a strong link between tamoxifen use and
      macular holes. Patients being commenced on tamoxifen should be advised of
      possible ocular complications and receive prompt ophthalmic review if symptoms
      develop.

PMID- 16983589
TI  - The Altemeier procedure: new technologies for an old technique.

PMID- 16983590
TI  - Infectious agents, inflammation, and growth factors: how do they interact in the
      progression or stabilization of mild human atherosclerotic lesions?
AB  - Advanced complicated atherosclerotic lesions have been related to many factors,
      including inflammation, infectious agents, and growth factors. Mycoplasma
      pneumoniae (MP) and Chlamydia pneumoniae (CP), inflammation, and growth factors
      have been associated with severe atherosclerotic lesions in necropsy material in
      recent work at our lab. The present study intends to clarify the pathogenesis of
      atherosclerosis, analyzing which of these elements (macrophages, MP, CP,
      lymphocytes, and growth factors) are associated with initial development of
      atherosclerotic lesions, discriminating elements related to stabilization of the
      plaque versus those related to subendothelial active accumulation of macrophages
      in living patients. Surgical ascending aorta fragments presenting mild
      atherosclerotic lesions from 30 coronary atherosclerotic patients were
      immunohistochemically quantified regarding CP, MP, T cells (CD4, CD8), B cells
      (CD20), macrophages (CD68), and growth factors [platelet-derived growth factor A
      (PDGF-A), PDGF-B, transforming growth factor-beta (TGF-beta), granulocyte
      macrophage colony-stimulating factor (GM-CSF)]. Cases were grouped according to
      the presence or not of active accumulation of macrophages at the subendothelium
      that indicates atheroma in development: group I (GI) fragments with <4 CD68+
      cells/x400 field, in normal distribution (mean 1.8 +/- 1) representing stable
      atherosclerotic mild lesion, and GII fragments presenting >or=4 CD68+ cells/x400
      field, in a non-normal distribution, mean (8.9 +/- 4.8, atheromas in progress),
      which was followed by increased number of lymphocytes. The median number in GI
      was significantly lower than that in GII: CD4 T (2.5 vs. 7.7), CD8 T (1.0 vs.
      5.5), and CD20 B (1.5 vs. 5.5) cells/x400 field, p < 0.001. Percentage area
      positive for CP antigens was significantly lower in GI than in GII: 1.0 vs. 9.2,
      p < 0.001. There was a higher percentage area occupied by MP than CP in both GI
      and GII (7.8 vs. 13.8). There was no difference regarding mean number of growth
      factor-positive cells/x400 field: PDGF-A, 1.4 vs. 3.9; PDGF-B, 3.4 vs. 5.7; TGF
      beta, 0.9 vs. 2.2; and GM-CSF, 2.0 vs. 2.2. Considering all cases, a positive
      correlation was seen between inflammatory cells and CP+ cells (r > 0.5 and p <
      0.01). Growth factors did not correlate with inflammatory cells, CP, or MP and
      were usually seen in smooth muscle cell and fibrotic areas. Study of initial
      atherosclerotic lesions showed that MP is present in both kinds of lesion: stable
      and active subendothelial accumulation of macrophages. Stabilization was related
      to proportional increase of both infectious agents, which were also related to
      increased amount of PDGF-A and PDGF-B. Active macrophage accumulation lesions
      were related to higher elevation in CP concentration at subendothelial regions,
      in association with B cells, but not of MP and growth factors. MP and CP,
      inflammation, and growth factors, which were already described in severe
      atherosclerotic lesions in necropsy material, are also present in mild lesions in
      living patients, strongly favoring a pathogenetic role for these bacteria in the
      pathogenesis of atherosclerosis. Predominance of CP in relation to MP may favor
      progression of the plaque, which is associated with increased B-cell
      proliferation. PDGF-A and PDGF-B are associated with plaque stability, at least
      in arterial segments not prone for development of complicated lesions.

PMID- 16983591
TI  - Perineal small bowel fistula after pelvic exenteration for cancer: technical
      guidelines for perineal fistula.
AB  - BACKGROUND: To determine guidelines for the management of perineal small bowel
      fistula (PSF) after total or posterior pelvic exenteration. METHODS: During 15
      years, 315 curative pelvic exenterations were performed. PSF occurred in 15
      patients (3.5%). We retrieved the precise modality of radiotherapy (fields and
      doses) and management of all patients (type of surgery, number of surgery and
      mortality). Delay of occurrence was divided in early (within 30 days or before
      hospital discharge) and delayed. RESULTS: All patients underwent surgery.
      Mortality rate was 13%. Fourteen patients (93%) had history of radiotherapy. No
      PSF was noted after anterior pelvic exenteration. Higher frequency of PSF was
      noted after total pelvic exenteration versus posterior pelvic exenteration (P =
      0.04). Early PSF occurred in four patients (27%) with higher frequency of small
      bowel intraoperative injury. Late PSF occurred in 11 patients (73%) divided in
      small bowel injury in contact with pelvic staples (n = 4) and disease recurrence
      (n = 6, local recurrence or carcinomatosis). One patient had delayed PSF by
      ulceration of small bowel in contact with pelvic drain. CONCLUSION: PSF was a
      life-threatening complication of pelvic exenteration. Radiotherapy leads to
      weaken small bowel with difficulty of cicatrisation. During pelvic exenteration:
      (a) extreme careful dissection and interposition of great omentum could avoid
      small bowel injury, (b) control of pelvic vessels and closure of rectum remnant
      should not used staplers. Intraoperative management of PSF used successful simple
      repair in case of early PSF or segmentary resection indeed enlarged to right
      colon in case of delayed PSF. Postoperative courses had to use intravenous
      hyperalimentation and digestive tract discharge.

PMID- 16983592
TI  - Surgical procedures after neoadjuvant chemotherapy in operable breast cancer:
      results of the GEPARDUO trial.
AB  - BACKGROUND: Neoadjuvant chemotherapy can increase the rate of breast-conserving
      surgery in patients with operable breast cancer. However, uncertainty remains
      regarding surgical procedures and predictors for successful breast-conserving
      surgery. METHODS: This study was an analysis of surgical data of a representative
      data subset of 607 patients enrolled in the GEPARDUO study. This prospective,
      multicenter, phase III study randomly assigned patients with operable breast
      cancer (> or = 2 cm) to neoadjuvant 8-week dose-dense doxorubicin plus docetaxel
      or a 24-week schedule of doxorubicin plus cyclophosphamide followed by docetaxel
      (AC-DOC). RESULTS: Breast conservation was attempted in 493 (81.2%) patients, but
      43 patients eventually required mastectomy, thus resulting in a breast-conserving
      surgery rate of 74.1%. Breast-conserving re-excision was performed in 61 patients
      (12.4%). Factors associated with a significantly higher breast-conserving surgery
      rate were a prechemotherapy tumor size < or = 40 mm, nonlobular histological
      characteristics, treatment with AC-DOC, clinical response, postchemotherapy tumor
      size < or = 20 mm, and treatment in a larger center (>10 enrolled patients).
      Nonlobular histological characteristics and intraoperative frozen-section
      analysis for margin evaluation were associated with significantly lower
      reoperation rates (P = .015). CONCLUSIONS: Breast conservation after neoadjuvant
      chemotherapy is feasible in most patients with operable breast cancer. For
      surgical planning, tumor characteristics and response to neoadjuvant chemotherapy
      should be taken into account. Improved breast-imaging modalities are necessary to
      improve detection of residual disease after neoadjuvant chemotherapy, especially
      when breast cancer is of lobular invasive histology. Margin assessment by
      intraoperative frozen-section analysis is helpful to avoid reoperation. To
      achieve an optimal result, an interdisciplinary surgical approach is important.

PMID- 16983593
TI  - Overcoming the shortage of transplantable organs: ethical and psychological
      aspects.
AB  - The main ethical problem of organ transplantation is the shortage of
      transplantable organs. The substitute strategies currently under discussion
      endanger frust in transplantion medicine and thereby increase the problem. Thus
      ethically preferable alternatives to overcome the shortage are suggested.

PMID- 16983594
TI  - Hypoglycaemic effect of Artemisia sphaerocephala Krasch seed polysaccharide in
      alloxan-induced diabetic rats.
AB  - The purpose of this study was to examine the hypoglycaemic activity of a new
      polysaccharide extracted from seed polysaccharide (ASP) was administered orally
      for 4 weeks and the blood glucose changes were determined in fasted rats. Plasma
      insulin, cholesterol and triglycerides levels were also determined. The ASP at a
      dose of 200 mg/kg body weight (bw) produced a significant decrease in blood
      glucose levels in diabetic rats (P <0.01). In the other hand, the effect of the
      ASP on the plasma cholesterol were also significant in diabetic rats (P <0.05).
      Furthermore, there was a significant effect of ASP on plasma triglycerides in
      both normal and diabetic groups. In order to characterise the active
      principle(s), which could be responsible for the therapeutic effect, a
      preliminary phytochemical analysis of the ASP was performed. The monosaccharides
      of ASP were composed of L-Ara, D-Xyl, D-Lyx, D-Man, D-Glc, D-Gal. Their molar
      proportions were 1, 4.98, 1.69, 27.86, 3.76 and 13.92, respectively.

PMID- 16983595
TI  - Tracheobronchial foreign body aspiration in children - diagnostic value of
      symptoms and signs.
AB  - OBJECTIVE: Tracheobronchial foreign body (TFB) aspiration is a common cause of
      respiratory compromise in early childhood. Research indicates that a high number
      of children are missed with TFB aspiration. The aim of this study was to identify
      predictors of potential TFB aspiration. STUDY DESIGN: We analysed 370 endoscopic
      reports of children admitted to our emergency department who underwent
      explorative rigid bronchoscopy to exclude/remove a TFB (1989-2003). Patient
      characteristics, history, clinical, radiographic and bronchoscopic findings were
      noted. Sensitivities and specificities for TFB aspiration were calculated for
      patient history, clinical and radiographic findings. RESULTS: The median age was
      1.8 years. In 59.7% of patients a TFB was found and removed. A group analysis was
      performed on children with symptoms less than 2 weeks (group A) and those more
      than 2 weeks (group B). The results showed that unilateral diminished breath
      sounds and unilateral overdistension on chest X-ray were the most sensitive (53
      79%) and specific (68-88%) findings in both groups. The clinical triad of acute
      choking/coughing, wheezing and unilateral diminished breath sounds had a high
      specificity (96-98%) in both groups. In contrast, a positive history of acute
      choking/coughing in group A or a permanent cough in group B showed a low
      specificity (8-16%). CONCLUSION: In a paediatric respiratory compromise, the
      presence of unilateral diminished breath sounds, pathological chest X-ray or
      clinical triad is a powerful indicator for occurred TFB aspiration. Since no
      single or combined variables can predict TFB aspiration with full certainty,
      bronchoscopic exploration should be performed if TFB aspiration is suspected.

PMID- 16983596
TI  - Early clinical experience with CardioCard - a credit card-sized electronic
      patient record.
AB  - QUESTIONS UNDER STUDY: CardioCard is a CDROM of credit card size containing
      medical information on cardiac patients. Patient data acquired during hospital
      stay are stored in PDF format and secured by a password known to patients only.
      In a consecutive series of patients, we assessed acceptance and utility of this
      new information medium. METHODS AND RESULTS: A questionnaire was sent to all
      patients who had received CardioCard over a one-year period. The questionnaire
      was returned by 392 patients (73%). 44% of patients had the card with them all
      the time. The majority of patients (73%) considered the CardioCard useful (8% not
      useful, 19% no statement) and most (78%) would even agree to bear additional
      costs. Only 5% worried about data security. In contrast, 44% would be concerned
      of data transmission via internet. During an observation period of 6 (SD 3)
      months, data were accessed by 27% of patients and 12% of their physicians. The
      proportion of card users was lower among older patients: < or = 50 years (y),
      39%; 51.60 y, 38%; 61.70 y, 26%; >70 y, 16% and particularly among older women:
      61.70 y, 9%; >70 y, 5%. Technical problems during data access occurred in 34%,
      mostly due to incorrect handling. CONCLUSIONS: A majority of patients considered
      CardioCard as useful and safe. Lack of hardware equipment or insufficient
      computer knowledge, but not safety issues were the most important limitations. As
      patients expressed concerns regarding protection of privacy if data were
      accessible via internet, this would remain a strong limiting factor for online
      use.

PMID- 16983597
TI  - Serum immunoglobin G4 (IgG4): an important marker in autoimmune pancreatitis?
AB  - A unique form of chronic pancreatitis has recently become widely recognised as an
      important clinical entity in the spectrum of pancreatic diseases under the term
      autoimmune pancreatitis (AIP). This entity is characterised by irregular
      narrowing of the pancreatic duct, swelling of parenchyma, lymphoplasmacytic
      infiltration and fibrosis as well as favourable response to corticosteroid
      treatment. In addition, increased concentration of serum immunoglobulin G4 (IgG4)
      is a notable characteristic marker. Some patients undergoing
      pancreaticoduodenectomy for presumed pancreatic ductal adenocarcinoma have
      instead been found to have AIP. Early recognition of AIP can prevent
      pancreaticoduodenectomy in these patients and effective treatment with steroids
      can be introduced. Based on an interesting case, we discuss the entity of AIP
      with the rare combination of sclerosing cholangitis and we focus on the relevance
      of serum IgG4 as a factor in diagnosis and monitoring therapy of AIP.

PMID- 16983598
TI  - The effects of triptolide on enteric mucosal immune responses of DBA/1 mice with
      collagen-induced arthritis.
AB  - For investigating the effects of triptolide on enteric mucosal immune responses
      of DBA/1 mice with collagen-induced arthritis (CIA), the changes of the Peyer's
      patches, IEL (intraepithelial lymphocytes), LPL (lamina propria lymphocytes),
      periphery lymphocytes, and levels of TGF-beta in CIA mice were checked with flow
      cytometry or ELISA. Our results showed that triptolide could lower the arthritic
      scores and increase TGF-beta level. Triptolide also had an effect on enteric
      mucosal immune lymphocytes in Peyer's patch, IEL and LPL of CIA mice. The
      regulation of enteric mucosal lymphocytes might explain some of the
      immunosuppressive activities of triptolide.

PMID- 16983600
TI  - Chirality influences the effects of linalool on physiological parameters of
      stress.
AB  - The specific physiological responses induced by inhaling R-(-)- as well as S-(+)
      linalool in 24 human subjects undergoing experimental stress were investigated in
      this study. Various physiological parameters of the autonomous nervous system
      (heart rate, blood pressure, electrodermal activity) as well as the endocrine
      system (salivary cortisol) were monitored. The study clearly indicated that
      odorants can modulate salivary cortisol levels, with both linalool enantiomers
      exerting relaxing effects. Concerning blood pressure and heart rate, S-(+)
      linalool acted as an activating agent in contrast to electrodermal activity. R-(
      )-linalool proved to be stress-relieving as determined by heart rate. In
      conclusion, the results revealed that (1) chirality crucially influences the
      physiological effects of odorants and that (2) odorants may act differently on
      certain physiological parameters.

PMID- 16983601
TI  - Inter-species variability of haplamine metabolism and identification of its phase
      I metabolites from liver microsomes.
AB  - Haplamine, a pyranoquinoline alkaloid, was isolated from the genus Haplophyllum.
      The inter-species variability of haplamine metabolism was determined by reversed
      phase high performance liquid chromatography (HPLC) with UV detection. Microsomes
      from the liver of rats, mice, rabbits, guinea-pigs and humans were incubated with
      haplamine. After incubation, samples were extracted with a mixture of ethyl
      acetate and isopropyl alcohol (90 : 10; v/v). Haplamine and its metabolites were
      separated by HPLC using Nucleosil C18 Nautilus (5 microm) connected with a
      precolumn of the same type. The HPLC mobile phase consisted of water (A) and a
      mixture of methanol and acetonitrile (85 : 15; v/v) (B) used in a gradient mode
      (17 to 27 % B for 10 min, 27 to 90 % B for 37 min, 90 to 17 % B for 3 min, and
      finally 17 % B for 3 min) at 1 mL/min. Quantitative and qualitative results
      showed significant inter-species differences in haplamine metabolism. Qualitative
      similarities were found between guinea-pigs, rabbits, and humans. The metabolites
      were isolated by HPLC and identified by GC/MS after silylation. The phase I
      metabolites identified in human liver microsomes were TRANS/CIS-3,4-dihydroxy-9-O
      desmethylhaplamine, TRANS/CIS-3,4-dihydroxyhaplamine and 9-O-desmethylhaplamine.

PMID- 16983602
TI  - Microarray detection of human parainfluenzavirus 4 infection associated with
      respiratory failure in an immunocompetent adult.
AB  - A pan-viral DNA microarray, the Virochip (University of California, San
      Francisco), was used to detect human parainfluenzavirus 4 (HPIV-4) infection in
      an immunocompetent adult presenting with a life-threatening acute respiratory
      illness. The virus was identified in an endotracheal aspirate specimen, and the
      microarray results were confirmed by specific polymerase chain reaction and
      serological analysis for HPIV-4. Conventional clinical laboratory testing using
      an extensive panel of microbiological tests failed to yield a diagnosis. This
      case suggests that the potential severity of disease caused by HPIV-4 in adults
      may be greater than previously appreciated and illustrates the clinical utility
      of a microarray for broad-based viral pathogen screening.

PMID- 16983603
TI  - Q fever in members of the United States armed forces returning from Iraq.
AB  - Large numbers of armed forces personnel returning from southwest Asia may present
      with infections that are not endemic to the United States or that occur rarely
      and are underdiagnosed in the United States. We report 2 cases of acute Q fever
      in members of the US Military recently returned from Iraq. Because a number of
      recent reports suggest that the risk of Q fever may be higher than initially
      thought among US forces deployed to this region, clinicians need to have a high
      index of clinical suspicion, an understanding of the available diagnostic tests,
      and knowledge regarding the methodology and capabilities of the laboratory to
      which specimens are submitted.

PMID- 16983604
TI  - Infective pyomyositis and myositis in children in the era of community-acquired,
      methicillin-resistant Staphylococcus aureus infection.
AB  - BACKGROUND: Cases of pyomyositis and myositis have been increasing in frequency
      at Texas Children's Hospital (Houston) since 2000. The increase appears to
      correlate with the emergence of community-acquired methicillin-resistant
      Staphylococcus aureus (MRSA). METHODS: The medical records of patients with
      pyomyositis and myositis hospitalized at Texas Children's Hospital during the
      period from January 2000 through December 2005 were reviewed. Available S. aureus
      isolates were obtained for susceptibility testing, to determine the presence of
      pvl (lukS-PV and lukF-PV), and for pulsed-field gel electrophoresis analysis.
      RESULTS: Forty-five previously healthy children with bacterial pyomyositis or
      myositis were analyzed. The causes were S. aureus (in 57.8% of children) and
      Streptococcus pyogenes (in 2.2%); 40.0% of children had negative culture results.
      The number of cases increased between 2000 and 2005, primarily as a result of an
      increase in the prevalence of community-acquired MRSA. The mean patient age was
      5.5 years (range, 0.06-15 years). The thigh (40.0% of children) and pelvis
      (28.9%) were the most commonly affected sites. The mean abscess diameter was 3.5
      cm. Eighteen children required at least 1 muscle drainage procedure. Of the 24
      available S. aureus isolates (15 community-acquired MRSA isolates and 9 community
      acquired, methicillin-susceptible S. aureus [MSSA] isolates), 16 were found to be
      USA300 by pulsed-field gel electrophoresis, and 17 carried pvl. Patients with
      community-acquired MRSA, USA300, and/or pvl-positive strains required more
      drainage procedures than did those with community-acquired MSSA, non-USA300,
      and/or pvl-negative strains (81% vs. 40% [P=.05], 82% vs. 29% [P=.02], and 81%
      vs. 38% [P=.07], respectively). CONCLUSIONS: Community-acquired MRSA is an
      increasing cause of pyomyositis and myositis in children. Community-acquired
      MRSA, USA300, pvl-positive S. aureus isolates caused more severe disease than did
      community-acquired MSSA, non-USA300, and pvl-negative isolates, respectively.

PMID- 16983605
TI  - Staphylococcus aureus small colony variants in prosthetic joint infection.
AB  - BACKGROUND: Small colony variants of Staphylococcus aureus tend to persist
      despite antimicrobial therapy, especially when involved in implant-associated
      infections. METHODS: We analyzed 5 cases of hip prosthesis-associated infections
      due to small colony variants, including their course prior to identification of
      the pathogen. Biopsy investigations included microbiological examination and, in
      1 case, transmission electron microscopy to detect intracellular bacteria in
      nonprofessional phagocytes. A treatment concept was elaborated on the basis of a
      published algorithm and patients were managed accordingly. RESULTS: The patients'
      mean age was 62.2 years. All patients experienced treatment failures prior to
      isolation of small colony variants, despite as many as 3 surgical revisions and
      up to 22 months of antibiotics. Transmission electron microscopy performed on
      biopsy specimens from periprosthetic tissue revealed intracellular cocci in
      fibroblasts. All prostheses were removed without implanting a spacer, and
      antimicrobial agents were administered for 5.5-7 weeks. Reimplantation of the
      prosthesis was performed for 4 patients. Follow-ups were uneventful in all 5
      cases. CONCLUSIONS: In the case of a poor response to adequate antimicrobial and
      surgical treatment in implant-associated staphylococcal infections, small colony
      variants should be considered and actively sought. In our case series, a 2-stage
      exchange without implantation of a spacer combined with antimicrobial therapy for
      an implant-free interval of 6-8 weeks was associated with successful outcome,
      with a mean follow-up of 24 months.

PMID- 16983606
TI  - Staphylococcus aureus small colony variants: difficult to diagnose and difficult
      to treat.

PMID- 16983607
TI  - Impact of routine intensive care unit surveillance cultures and resultant barrier
      precautions on hospital-wide methicillin-resistant Staphylococcus aureus
      bacteremia.
AB  - BACKGROUND: Serial interventions are often used to reduce the risk of health care
      associated methicillin-resistant Staphylococcus aureus (MRSA) infections. To our
      knowledge, the relative impact of these interventions has not previously been
      ascertained. METHODS: We conducted a retrospective study of 4 major infection
      control interventions using an interrupted time series design to evaluate their
      impact on MRSA bacteremia in an 800-bed hospital with 8 intensive care units
      (ICUs). Interventions were introduced 1 at a time during a 9-year period and
      involved the promotion of compliance with maximal sterile barrier precautions
      during central venous catheter placement, the institution of alcohol-based hand
      rubs for hand disinfection, the introduction of a hand hygiene campaign, and the
      institution of routine nares surveillance cultures for MRSA in all ICUs for
      patients on ICU admission and weekly thereafter while in the ICU. Positive
      cultures resulted in the initiation of contact isolation precautions. Using
      segmented regression analyses, we evaluated changes in monthly incidence and
      prevalence of MRSA bacteremia from their predicted values. Methicillin
      susceptible Staphylococcus aureus bacteremia was monitored as a control. RESULTS:
      Routine surveillance cultures and subsequent contact isolation precautions
      resulted in substantial reductions in MRSA bacteremia in both ICUs and non-ICUs.
      In 16 months, the incidence density of MRSA bacteremia decreased by 75% in ICUs
      (P=.007) and by 40% in non-ICUs (P=.008), leading to a 67% hospital-wide
      reduction in the incidence density of MRSA bacteremia (P=.002). Methicillin
      susceptible S. aureus bacteremia rates remained stable during this time. The
      other interventions were not associated with a statistically significant change
      in MRSA bacteremia. CONCLUSIONS: Routine surveillance for MRSA in ICUs allowed
      earlier initiation of contact isolation precautions and was associated with large
      and statistically significant reductions in the incidence of MRSA bacteremia in
      the ICUs and hospital wide. In contrast, no similar decrease was attributable to
      the other infection control interventions.

PMID- 16983608
TI  - Risk factors for recurrent melioidosis in northeast Thailand.
AB  - BACKGROUND: Recurrent melioidosis occurs in approximately 6% of patients in the
      first year following the initial presentation. A recent study revealed that 25%
      of patients with recurrence had reinfection rather than a relapse resulting from
      a failure to cure. The aim of this study was to reevaluate these 2 patient groups
      to define their individual risk factors. METHODS: All adult patients who
      presented to Sappasithiprasong Hospital (Ubon Ratchathani, in northeast Thailand)
      with culture-confirmed melioidosis during the period 1986-2004 and who survived
      to receive oral antimicrobial therapy were observed until July 2005. Clinical
      factors and antimicrobial treatment of patients with recurrent disease due to
      relapse or reinfection, as confirmed by bacterial genotyping, were compared using
      a time-varying Cox proportional hazard model. RESULTS: Of 889 patients who
      survived and underwent follow-up, 86 patients (9.7%) presented with relapse, and
      30 patients (3.4%) became reinfected. There was no difference in acute outcome
      between the relapse and reinfection groups. No risk factors for reinfection were
      identified. Multivariate analyses identified choice and duration of oral
      antimicrobial therapy as the most important determinants of relapse, followed by
      positive blood culture result (hazard ratio [HR], 1.86; 95% confidence interval
      [CI], 1.18-2.92) and multifocal distribution (HR, 1.95; 95% CI, 1.03-3.67).
      Patients treated with an appropriate oral antibiotic regimen for 12-16 weeks had
      a 90% decreased risk of relapse (HR, 0.10; 95% CI, 0.02-0.44), compared with
      patients who were treated for < or = 8 weeks. Trimethoprim-sulfamethoxazole plus
      doxycycline was an effective oral therapy. CONCLUSIONS: This study highlights
      clinical factors associated with an increased likelihood of relapse and provides
      evidence for optimal oral antimicrobial therapy.

PMID- 16983609
TI  - Arthritis due to Mycobacterium xenopi: a retrospective study of 7 cases in
      France.
AB  - BACKGROUND: Mycobacterium xenopi is a nontuberculous mycobacterium responsible
      for opportunistic and nosocomial infections, chiefly of the lung; few cases of
      bone and joint infection have been reported. From July 1989 through May 1993, an
      outbreak of 58 cases of nosocomial discitis due to M. xenopi infection following
      percutaneous nucleotomy occurred in a French hospital. Peripheral M. xenopi
      arthritis seems exceedingly rare. We conducted a study to assess the
      epidemiological and clinical patterns of M. xenopi arthritis. METHODS: We
      retrospectively reviewed cases of M. xenopi arthritis reported from May 1993
      through October 2004. RESULTS: We identified 7 cases, all of which occurred after
      invasive surgical procedures were performed on the affected joint, suggesting a
      nosocomial pattern of infection. Two patients may have been contaminated at the
      hospital where the M. xenopi discitis outbreak occurred. No source was identified
      in the other 5 patients. Despite the probable nosocomial nature of the
      infections, the diagnosis was delayed (mean time until diagnosis, 50 months).
      Repeated collection of deep tissue specimens for bacteriological analysis seemed
      crucial to the diagnosis. The treatment relied on combination antimicrobial
      therapy and surgery. Among 11 cases of M. xenopi osteoarticular infection
      reported in the literature from 1975 to 2005, (arthritis in 9 cases and osteitis
      in 2), none were nosocomial. CONCLUSION: A high index of suspicion should be
      maintained to ensure the diagnosis of M. xenopi arthritis before chronic
      monoarthritis and before the development of irreversible joint damage.

PMID- 16983610
TI  - Placental enlargement in women with primary maternal cytomegalovirus infection is
      associated with fetal and neonatal disease.
AB  - BACKGROUND: Serological testing for primary maternal cytomegalovirus (CMV)
      infection during pregnancy is not routine, but ultrasound studies are routine.
      Therefore, we evaluated placental thickening in women with primary CMV infection
      during pregnancy. METHODS: The study included 92 women with primary CMV infection
      during pregnancy and 73 CMV-seropositive pregnant women without primary CMV
      infection. Neonatal CMV transmission was determined by CMV culture of urine
      samples. Thirty-two women were treated with CMV hyperimmune globulin to either
      prevent or treat intrauterine CMV infection. Maximal placental thickness was
      measured by longitudinal (nonoblique) scanning with the ultrasound beam
      perpendicular to the chorial dish. Programmed placental ultrasound evaluations
      were performed from 16 to 36 weeks of gestation. RESULTS: At each measurement
      between 16 and 36 weeks of gestation, women with primary CMV infection who had a
      fetus or newborn with CMV disease had placentas that were significantly thicker
      than those of women with primary CMV infection who did not have a diseased fetus
      or newborn (P<.0001); the latter group, in turn, had placentas that were
      significantly thicker than those of seropositive control subjects (P<.0001). For
      both women with and women without diseased fetuses or newborns, receipt of
      hyperimmune globulin after primary CMV infection was associated with
      statistically significant reductions in placental thickness (P<.001). Placental
      vertical thickness values, which are predictive of primary maternal infection,
      were observed at each measurement from 16 to 36 weeks of gestation, and cutoff
      values ranged from 22 mm to 35 mm, with the best sensitivity and specificity at
      28 and 32 weeks of gestation. CONCLUSIONS: Primary maternal CMV infection and
      fetal or neonatal disease are associated with sonographically thickened
      placentas, which respond to administration of hyperimmune globulin. These
      observations suggest that many of the manifestations of fetal and neonatal
      disease are caused by placental insufficiency.

PMID- 16983611
TI  - The role of the placenta in the pathogenesis of congenital cytomegalovirus
      infection: is the benefit of cytomegalovirus immune globulin for the newborn
      mediated through improved placental health and function?

PMID- 16983612
TI  - Effect of pneumococcal vaccination: a comparison of vaccination rates in patients
      with bacteremic and nonbacteremic pneumococcal pneumonia.
AB  - BACKGROUND: Despite the widespread acceptance of the 23-valent pneumococcal
      capsular polysaccharide vaccine (PPV), its protective effect continues to be
      disputed. We describe a novel approach to examine the protective effect of this
      vaccine. METHODS: We recorded the vaccination status of every patient for whom a
      culture yielded Streptococcus pneumoniae during a 4.5-year period, comparing
      rates of prior PPV administration in patients with (1) bacteremic pneumococcal
      pneumonia, (2) all-invasive pneumococcal disease, (3) nonbacteremic pneumococcal
      pneumonia, (4) acute exacerbation of chronic bronchitis (AECB) due to S.
      pneumoniae, and (5) pneumococcal colonization. The principal comparisons were
      with patients who had bacteremic pneumonia or any invasive pneumococcal disease
      and those with nonbacteremic pneumococcal pneumonia. We also compared vaccination
      rates in patients who had nonbacteremic pneumonia with vaccination rates in
      patients with AECB or pneumococcal colonization. RESULTS: The rate of prior PPV
      vaccination was lower among patients with bacteremic pneumococcal pneumonia
      (39.7%) or any invasive pneumococcal disease (38.0%) than among patients with
      nonbacteremic pneumonia (57.6%), AECB (60.0%), or pneumococcal colonization
      (57.8%). PPV conferred a 54% protection rate against bacteremic versus
      nonbacteremic pneumococcal pneumonia. There was no apparent protection against
      nonbacteremic pneumonia compared, for example, with colonized persons or with
      those who had AECB. CONCLUSIONS: PPV provides moderate protection against
      invasive pneumococcal disease but does not protect against nonbacteremic
      pneumococcal pneumonia. These findings suggest the importance of a continued
      search for a better pneumococcal vaccine.

PMID- 16983613
TI  - A prospective hospital-based study of the clinical impact of non-severe acute
      respiratory syndrome (Non-SARS)-related human coronavirus infection.
AB  - BACKGROUND: In addition to the human coronaviruses (HCoVs) OC43 and 229E, which
      have been known for decades to cause infection in humans, 2 new members of this
      genus have recently been identified: HCoVs NL63 and HKU1. Their impact as a cause
      of respiratory tract disease in adults at risk for complications needs to be
      established. METHODS: We prospectively assessed the clinical impact of
      coronavirus infection (excluding cases of severe acute respiratory syndrome)
      among hospitalized adults. All patients with respiratory disease for whom
      bronchoalveolar lavage was performed were screened by reverse-transcriptase
      polymerase chain reaction for the presence of all 4 HCoVs. RESULTS: HCoV was
      identified in 29 (5.4%) of 540 bronchoalveolar lavage fluid specimens from 279
      subjects (mean age, 51 years; 63% male). HCoV OC43 was identified most frequently
      (12 isolates), followed by 229E (7 isolates), NL63 (6 isolates), and HKU1 (4
      isolates). In all, 372 (69%) of 540 bronchoalveolar lavage fluid specimens were
      negative for bacteria, and 2 persons were coinfected with other respiratory
      viruses. Transplantation was the most common underlying condition. Of the 29
      patients who had HCoV identified in their bronchoalveolar lavage fluid specimens,
      9 (31%) were hospitalized in the intensive care unit, 22 (76%) presented to the
      hospital with acute respiratory symptoms, 16 (55%) presented with cough and/or
      sputum, 13 (45%) presented with dyspnea, 16 (55%) had experienced prior
      respiratory infection, and 18 (62%) had a new infiltrate that was visible on
      chest radiograph. The most frequent final diagnosis was a lower respiratory tract
      infection. CONCLUSIONS: The recently discovered HCoVs NL63 and HKU1 contribute
      significantly to the overall spectrum of coronavirus infection. Our study also
      suggests that coronaviruses contribute to respiratory symptoms in most cases.

PMID- 16983614
TI  - Seasonal trends of human parainfluenza viral infections: United States, 1990
      2004.
AB  - BACKGROUND: Human parainfluenza viruses (HPIVs) are important causes of upper and
      lower respiratory tract illness among children and adults. METHODS: We describe
      seasonal trends for individual HPIV serotypes and respiratory syncytial virus in
      the United States using data on the percentage of specimens with positive test
      results reported to the National Respiratory and Enteric Viruses Surveillance
      System during the period 1990-2004. Onset and conclusion dates for peaks in
      activity were determined with the Early Aberration Reporting System's cumulative
      sum method C2 by detecting periods when the number of positive HPIV test results
      was significantly greater than that observed for preceding weeks for each
      serotype. RESULTS: During the study period, increases in the percentage of
      positive HPIV-3 and HPIV-2 test results occurred annually during April-June and
      October-November, respectively. Increases in the percentage of positive HPIV-1
      test results occurred biennially during September-December during odd-numbered
      years. During years when HPIV-1 was not circulating, more HPIV-3 activity was
      reported, either as a longer spring season or as a second smaller period of
      increased activity noted in the fall. Seasonal peaks in respiratory syncytial
      virus activity occurred annually during November-April. CONCLUSIONS: We provide a
      national perspective for HPIV activity during the 15-year study period and
      demonstrate distinct seasonal peaks in activity for HPIV-1, HPIV-2, and HPIV-3.
      In addition, our data suggest that there is an interaction between HPIV-3 and
      HPIV-1 activity, which may have implications in future prevention strategies.

PMID- 16983615
TI  - Slower rates of clearance of viral load and virus-containing immune complexes in
      patients with dengue hemorrhagic fever.
AB  - BACKGROUND: Although previous studies have revealed the contribution of an
      initial high level of dengue virus replication to the severe and potentially life
      threatening diseases dengue hemorrhagic fever (DHF) and dengue shock syndrome,
      the involvement of dengue virus in the immunopathological processes during the
      transition from fever to defervescence, which is a critical stage in determining
      the progression to DHF, has not been appreciated. Previously, we reported that
      dengue virus can be detected in the immune complexes of patients with DHF during
      this period. METHODS: We investigated plasma dengue viral load, virus in immune
      complexes, antibody response, complements, and cytokines for 54 patients with
      dengue fever (a relatively mild form of disease) and 49 patients with DHF. The
      patients had confirmed secondary infection with dengue virus type 2 from a large
      outbreak in southern Taiwan in 2002. RESULTS: Patients with DHF had a
      significantly higher viral load and a slower rate of clearance than patients with
      dengue fever. For viral loads >5.7 log RNA copies/mL on the day of defervescence,
      the positive and negative predictive values for DHF are 0.88 and 0.95,
      respectively. A higher level and slower decline of dengue virus-containing immune
      complexes (and a subsequently higher elevation of C5a and soluble interleukin 2
      receptor) were found in patients with DHF, compared with patients with dengue
      fever. CONCLUSIONS: These findings indicate that slower rates of clearance of
      viral load and virus-containing immune complexes are associated with subsequent
      immune activation and contribute to the progression of DHF at this critical
      stage. Moreover, viral load on the day of defervescence can predict cases of DHF.

PMID- 16983617
TI  - Human milk vacuolating cytotoxin A immunoglobulin A antibodies modify
      Helicobacter pylori infection in Gambian children.
AB  - We collected data, including the weights, urea breath test results, and presence
      of maternal milk cytotoxin-associated gene-specific and vacuolating cytotoxin A
      specific immunoglobulin A monthly from 48 mothers and infants (to 44 weeks of
      age) in The Gambia. In all, 11 children (23%) had negative urea breath test
      results, and 37 (77%) had positive results. Weight loss associated with
      Helicobacter pylori colonization was restricted to children whose mothers did not
      produce anti-vacuolating cytotoxin A antibodies in their milk (P=.028, by t
      test).

PMID- 16983616
TI  - Clinical research in the lay press: irresponsible journalism raises a huge dose
      of doubt.

PMID- 16983618
TI  - A 33-year-old man with a white pupil.

PMID- 16983619
TI  - In harm's way: infections in deployed American military forces.
AB  - Hundreds of thousands of American service members have been deployed to
      Afghanistan and Iraq since 2001. With emphasis on the common infections and the
      chronic infections that may present or persist on their return to the United
      States, we review the data on deployment-associated infections. These infections
      include gastroenteritis; respiratory infection; war wound infection with
      antibiotic-resistant, gram-negative bacteria; Q fever; brucellosis; and parasitic
      infections, such as malaria and leishmaniasis.

PMID- 16983620
TI  - Interactions between natural health products and antiretroviral drugs:
      pharmacokinetic and pharmacodynamic effects.
AB  - Concurrent use of natural health products (NHPs) with antiretroviral drugs (ARVs)
      is widespread among human immunodeficiency virus-infected patients. This article
      reviews the clinical pharmacokinetic and pharmacodynamic interactions between
      NHPs and ARVs. Many NHPs are complex mixtures and are likely to contain organic
      compounds that may induce and/or inhibit drug metabolizing enzymes and drug
      transporters. Although the weight of evidence for the effects of certain NHPs
      varies and many studies of these products lack scientific rigor, it has been
      observed that St. John's wort clearly induces cytochrome P450 3A4 and P
      glycoprotein and reduces protease inhibitor and nonnucleoside reverse
      transcriptase inhibitor concentrations, thereby increasing the likelihood of
      therapeutic failure. Limited clinical research suggests that intake of garlic and
      vitamin C results in reductions in ARV concentrations. The intake of milk
      thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in
      vitro and may increase ARV concentrations, but by clinically unimportant amounts.
      Intake of fish oil reduces ARV-induced hypertriglyceridemia without significantly
      affecting lopinavir concentrations. Before recommending the use of NHPs as
      adjuncts to ARV use, studies should first exclude significant pharmacokinetic
      interactions and ensure that ARV efficacy is maintained.

PMID- 16983621
TI  - New agents for the treatment of fungal infections: clinical efficacy and gaps in
      coverage.
AB  - The incidence of fungal infections has increased globally, and the introduction
      of the newer triazoles and echinocandin antifungals is a more-than-welcome and
      long overdue development. In this report, we review the clinical trials
      evaluating the therapeutic efficacy of these new antifungal agents and examine
      possible gaps in coverage. Voriconazole has become the primary treatment for most
      forms of invasive aspergillosis in a number of centers, posaconazole offers a
      broad antifungal spectrum, and echinocandins are fungicidal against most Candida
      species. Moreover, the new agents are active against some fungi that are
      resistant to amphotericin B, may have a role in the management of fever and
      neutropenia, and provide exciting options for combination antifungal therapy.
      However, significant questions remain, including the management of breakthrough
      infections and treatment failures and the efficacy of the new antifungal agents
      against less common fungi.

PMID- 16983622
TI  - Symptomatic relapse of HIV-associated cryptococcal meningitis after initial
      fluconazole monotherapy: the role of fluconazole resistance and immune
      reconstitution.
AB  - BACKGROUND: Cryptococcal meningitis (CM) in South Africa is often treated with
      fluconazole as initial therapy. Surveillance data suggest that the prevalence of
      fluconazole-resistant CM is increasing, and expanding access to antiretroviral
      therapy is resulting in increasing recognition of immune reconstitution
      inflammatory syndrome. Therefore, we conducted a study to assess the contribution
      of these factors to CM relapse in this context. METHODS: Patients with
      symptomatic relapse of CM were prospectively identified at 2 hospitals in Cape
      Town, South Africa, during the period of 2003-2005. Patients met the following
      criteria: (1) a previous laboratory-confirmed episode of CM, with resolution of
      symptoms after treatment; (2) reported adherence to fluconazole treatment; (3)
      recurrence of typical CM symptoms; (4) cerebrospinal fluid antigen test and/or
      culture positive for Cryptococcus neoformans; and (5) no alternative diagnosis.
      Data on patients' human immunodeficiency virus (HIV) and CM infections and
      treatment were collected and analyzed. RESULTS: Thirty-two episodes of relapse
      occurred among 27 patients. Episodes were classified into 3 groups: culture
      positive episodes in antiretroviral therapy-naive patients (6 episodes), culture
      positive episodes in patients receiving antiretroviral therapy (15 episodes), and
      culture-negative episodes in patients receiving antiretroviral therapy (11
      episodes). Seventy-six percent of culture-positive relapses were associated with
      isolates that had reduced susceptibility to fluconazole. Drug-resistant cases
      required prolonged intravenous therapy with amphotericin B, and despite this
      treatment, the mortality rate was high (54% at a median of 6 months of follow
      up). Despite a long interval between initiation of antifungal therapy and
      initiation of antiretroviral therapy (median interval, 144 days), immune
      reconstitution inflammatory syndrome contributed to at least one-third of
      relapses. CONCLUSIONS: After initial treatment with fluconazole, relapses of
      symptomatic CM are often associated with fluconazole resistance and immune
      reconstitution inflammatory syndrome. These data add to concern about the
      efficacy of fluconazole, compared with amphotericin B, for initial treatment of
      HIV-associated CM.

PMID- 16983623
TI  - Free fluconazole for cryptococcal meningitis: too little of a good thing?

PMID- 16983624
TI  - Cryptococcus gattii infection: characteristics and epidemiology of cases
      identified in a South African province with high HIV seroprevalence, 2002-2004.
AB  - We describe 46 Cryptococcus gattii-infected persons identified by population
      based surveillance conducted in South Africa. Most patients with C. gattii
      infection presented with meningitis. The mortality rate during hospitalization
      was 36%. We found no significant differences between persons with and persons
      without C. gattii infection with regard to clinical presentation, acquired
      immunodeficiency syndrome diagnosis, concomitant conditions, or prior
      opportunistic infections. C. gattii isolates had low MICs to the tested
      antifungal drugs.

PMID- 16983626
TI  - Mycograb for the treatment of invasive candidiasis.

PMID- 16983627
TI  - Osteopenia in patients with HIV infection is not associated with elevated sTNFR2
      levels.

PMID- 16983628
TI  - Antibiotic pricing: when cheaper may not be better.

PMID- 16983629
TI  - Nitric oxide and endothelial dysfunction in HIV type 1 infection.

PMID- 16983630
TI  - Quantitative-competitive polymerase chain reaction coupled with slab gel and
      capillary electrophoresis for the detection of roundup ready soybean and maize.
AB  - The aim of the present study was to develop a quantitative-competitive PCR (QC
      PCR) method to detect DNA from transgenic herbicide-resistant (roundup ready, RR)
      soybean and maize. Since no QC-PCR system for the quantification of RR maize had
      been published at the time of writing, a specific competitor DNA for transgenic
      event was developed. For the QC-PCR of RR-soybean, a commercially available
      competitor was employed. These internal standards were calibrated by coamplifying
      with mixtures containing RR-soybean and maize DNAs. The calibrated QC-PCR systems
      were applied to certified RR-soybean and maize flour mixtures in order to
      demonstrate their suitability not only for the quantification of the glyphosate
      resistance traits in DNA matrices, but also in practically relevant samples. In
      addition, a special focus of the present work was to compare the detection of QC
      PCR products by slab gel and CGE with UV detection. CGE permitted the precise
      detection of transgenic events also below the equivalence points; while in slab
      gel electrophoresis, due to the low sensitivity the quantification of genetically
      modified DNA was allowed only at the equivalence point.

PMID- 16983631
TI  - Sensitive determination of carbohydrates labelled with p-nitroaniline by
      capillary electrophoresis with photometric detection using a 406 nm light
      emitting diode.
AB  - p-Nitroaniline was explored as a derivatising reagent for UV absorbance detection
      of carbohydrates after separation by CE. This derivatising agent has three
      advantages: first, it has excellent water solubility; second, it has high molar
      absorptivity; and third, it is possible to obtain sensitive detection using a UV
      or blue light-emitting diode (LED) as the light source. The labelling reaction
      took less than 30 min to complete with high reaction yield. The separation
      process was modelled and optimised using an artificial neural network. Nine
      carbohydrates were separated by a CE system within 16 min using a 0.17 M boric
      acid buffer at pH 9.7. On-column LED detection at 406 nm allowed the detection of
      carbohydrates with good detection limits (<1.1 microM or 8.8 fmol) and
      reproducible quantification in the concentration range of 2.6-200 microM. This
      method was applied successfully to the determination of component carbohydrates
      in some food samples.

PMID- 16983632
TI  - Adaptive contrast enhancement of two-dimensional electrophoretic protein gel
      images facilitates visualization, orientation and alignment.
AB  - 2-DE is a powerful technique to discriminate post-translationally modified
      protein isoforms. However, all steps of 2-DE preparation and gel-staining may
      introduce unwanted artefacts, including inconsistent variation of background
      intensity over the entire 2-DE gel image. Background intensity variations limit
      the accuracy of gel orientation, overlay alignment and spot detection methods. We
      present a compact and efficient denoising algorithm that adaptively enhances the
      image contrast and then, through thresholding and median filtering, removes the
      gray-scale range covering the background. Applicability of the algorithm is
      demonstrated on immunoblots, isotope-labeled gels, and protein-stained gels.
      Validation is performed in contexts of (i) automatic gel orientation based on
      Hough transformation, (ii) overlay alignment based on cross correlation and (iii)
      spot detection. In gel stains with low background variability, e.g. Sypro Ruby,
      denoising will lower the spot detection sensitivity. In gel regions with high
      background levels denoising enhances spot detection. We propose that the
      denoising algorithm prepares images with high background for further automatic
      analysis, without requiring manual input on a gel-to-gel basis.

PMID- 16983633
TI  - Cholesterol-rich membrane coatings for interaction studies in capillary
      electrophoresis: application to red blood cell lipid extracts.
AB  - The purpose was to develop a stable biological membrane coating for CE useful for
      membrane interaction studies. The effect of cholesterol (chol) on the stability
      of dipalmitoylphosphatidylcholine (DPPC) and sphingomyelin (SM) coatings was
      studied. In addition, a fused-silica capillary for CE was coated with human red
      blood cell (RBC) ghost lipids. Liposomes prepared of DPPC/SM with and without
      chol or RBC ghost lipids were flushed through the capillary and the stability of
      the coating was measured electrophoretically. Similar mixtures of DPPC/SM with
      and without chol were further studied by differential scanning calorimetry. The
      presence of phosphatidylcholine as a basic component in the coating solution of
      DPPC/SM/chol was found to be essential to achieve a good and stable coating. The
      results also confirmed the stability of coatings obtained with solutions of DPPC
      with 0-30 mol% of chol and SM in different ratios, which more closely resemble
      natural membranes. Finally, the electrophoretic measurements revealed that a
      stable coating is formed when capillaries are coated with liposomes of RBC ghost
      lipids.

PMID- 16983634
TI  - Preparation and evaluation of C18-bonded 1-microm silica particles for
      pressurized capillary electrochromatography.
AB  - Nonporous silica spheres (1 microm) were synthesized and bonded with
      octadecylsilane functionality. These stationary phase particles were packed
      electrokinetically into fused-silica capillaries with 100 microm id for a length
      of 20 cm, which was evaluated by using pressurized CEC (pCEC). The efficiency of
      the C18 RP column was characterized through the theoretical plates of thiourea,
      benzyl alcohol, toluene, styrene, and naphthalene. The effects of experimental
      parameters such as the applied voltage, sample size, pump flow rate, pH value and
      the concentration of the buffer solution, and the content of methanol in the
      mobile phase, on-column efficiency were evaluated. Column efficiency as high as
      200 000 theoretical plates per meter for naphthalene was obtained with the
      optimal condition of 70% v/v methanol and 30% v/v of 10 mmol/L phosphate buffer
      (pH 7.8) at an applied voltage of 10 kV and a supplementary pressure of 500 psi.

PMID- 16983635
TI  - Agarose isoelectric focusing can improve resolution of membrane proteins in the
      two-dimensional electrophoresis of bacterial proteins.
AB  - 2-D separation of bacterial membrane proteins is still difficult despite using
      high-resolution IPG-IEF/SDS-PAGE. We were searching for alternative methods to
      avoid typical problems such as precipitation, low solubility, and aggregation of
      membrane proteins in the 1-D separation with IPG-IEF. Blue native electrophoresis
      (BNE) and agarose IEF (A-IEF) were tested for their separation capacity and their
      capability of replacing IPG-IEF in the first dimension. SDS-PAGE was chosen for
      the second dimension on account of its outstanding resolution. We could confirm
      that only A-IEF was a useful replacement for the IPG-IEF in the first dimension
      resulting in 2-D protein distributions with additional membrane protein spots not
      being found after IPG-IEF/SDS-PAGE. A second interesting result was that the
      agarose IEF mediates the possibility of separation of membrane proteins in a
      partially native state in the first dimension. This native A-IEF resulted in
      drastically changed spot patterns with an acidic shift of nearly all spots and
      divergent distribution of proteins compared to non-native A-IEF and IPG-IEF. We
      found out that native and non-native A-IEF are powerful tools to supplement IPG
      IEF/SDS-PAGE.

PMID- 16983636
TI  - Effect of barium tetraborate on the separation of tryptic digests of proteins by
      zone electrophoresis in uncoated capillaries.
AB  - A simple, fast, efficient and reproducible method for peptide separations in CZE
      is reported. It consists in running tryptic digests of peptides in an uncoated
      capillary, in a BGE composed of tetraborate as a buffering ion, in which the
      typical sodium counterion is substituted with barium. Efficient absorption of
      this divalent cation to ionized silanols and barium silicate precipitation seem
      to be able to shield effectively the silica surface from separands. This is
      demonstrated by the fact that, when tBa(2+) ions are present in solution (from pH
      8.5 up to pH 11.0), the electroendoosmotic flow is reversed; such reversal being
      progressively higher at higher pH values, by up to a four-fold. Separations
      become progressively better at higher pH values, whereas at pH 11 in sodium
      tetraborate they are dramatically worsened. It is further hypothesized that the
      barium silicate layer further protects the silica surface against dissolution and
      corrosion which is quite substantial at pH 11.

PMID- 16983637
TI  - Capillary electrophoresis of liposomes functionalized for protein binding.
AB  - CE enabled assessing the attachment of hexa-histidine-tagged proteins to
      functionalized phospholipid liposomes. The liposomes were made of 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine, phosphatidyl-ethanolamine, cholesterol and
      distearoyl-glycero-3-phosphoethanolamine-N-methoxy(polyethylene glycol) in a
      molar ratio of 29:26:40:5. The unilamellar vesicles, which had an average
      diameter of 170 nm, were labelled by inclusion of FITC-dextran for fluorescence
      detection. CE was carried out in poly(vinyl alcohol) (PVA)-coated capillaries at
      25 degrees C with a BGE consisting of Tris-HCl (50 mM, pH 8.0). For conjugation
      of the liposomes with the proteins (soluble synthetic receptor fragments with
      molecular mass of 60 and 70 kDa, respectively), Ni(2+) was implanted into the
      vesicle surface by an anchor lipid containing a nitrilotriacetate acid (NTA)
      group as complexation agent for the metal ions. The difference in surface charge
      enabled the separation of the different species of interest by CE: plain
      vesicles, vesicles functionalised with Ni-NTA, vesicle-protein complexes and the
      species formed upon removal of the Ni-ions by complexation with EDTA. Loss of the
      Ni-ions resulted in the release of the proteins and the reappearance of the plain
      Ni-free NTA-liposome species in the electropherograms.

PMID- 16983638
TI  - An integrated micropump and electrospray emitter system based on porous silica
      monoliths.
AB  - The work presents the design of an integrated system consisting of a high
      pressure electroosmotic (EO) micropump and a microporous monolithic emitter,
      which together generate a stable and robust electrospray. Both the micropump and
      electrospray emitter are fabricated using a sol-gel process. Upon application of
      an electric potential of sufficient amplitude (>2 kV), the pump delivers fluids
      with an electroosmotically induced high pressure (>1 atm). The same potential is
      also harnessed to electrostatically generate a stable electrospray at the porous
      emitter. Electrokinetic coupling between pump and spray produces spray features
      different from sprays pressurized by independent mechanical pumps. Four typical
      spray modes, each with different drop sizes and charge-to-mass ratios, are
      observed and have been characterized. Since the monolith is silica-based, this
      integrated device can be used for a variety of fluids, especially organic
      solvents, without the swelling and shrinking problems that are commonly
      encountered for polymer monoliths. The maximum pressure generated by a 100 microm
      id monolithic pump is 3 atm at an applied voltage of 5 kV. The flow rate can be
      adjusted in the range of 100 nL/min to 1 microL/min by changing the voltage. For
      a given applied voltage across the pump and emitter system, it is seen that there
      exists one unique flow rate for which flow balance is achieved between the
      delivery of liquid to the emitter by the pump and the liquid ejection from the
      emitter. Under such a condition, a stable Taylor cone is obtained. The principles
      that lead to these results are also discussed.

PMID- 16983639
TI  - Electrochromatographic behavior of silica monolithic capillaries of different
      skeleton sizes synthesized with a simplified and shortened sol-gel procedure.
AB  - Silica monolithic capillaries (SMCs) were synthesized by a sol-gel process.
      First, a simplification of the synthesis was proposed by replacing the
      calcination and the drying steps which can have tremendous effects on
      chromatographic and physical properties, by a single water or methanol 2 h
      washing step. The efficiency of such a washing step was demonstrated and the
      comparison of the chromatographic and electrochromatographic properties between
      calcined and washed SMCs has shown that such a modification did not impair
      retention, efficiency, and stability of the monolith. This simplified procedure
      was carried out to synthesize SMCs with two different skeleton sizes. These
      capillaries were evaluated in electrochromatography and present high efficiencies
      (H = 5 microm) at least equal to the best ones reported in the literature.
      Furthermore, the influence of the skeleton size on the EOF of the second kind
      (EOF-2) was investigated with unmodified SMCs used under various experimental
      conditions including electrical field strength and buffer concentration. The
      ionic strength of the mobile phase and the applied electrical field that enable
      this EOF-2 were related to the size of the skeleton which was tuned by the
      synthesis conditions.

PMID- 16983640
TI  - Capillary electrophoresis with a UV light-emitting diode source for chemical
      monitoring of native and derivatized fluorescent compounds.
AB  - We report the utilization of a high power UV light-emitting diode for
      fluorescence detection (UV-LED-IF) in CE separations. CE-UV-LED-IF allows
      analysis of a range of environmentally and biologically important compounds,
      including PAHs and biogenic amines, including neurotransmitters, amino acids,
      proteins, and peptides, that have been derivatized with UV-excited fluorogenic
      labels, e.g., o-phthalic dicarboxaldehyde/beta-mercaptoethanol (OPA/beta-ME). The
      365 nm UV-LED was used as a stable, low cost source for detection of UV-excited
      fluorescent compounds. UV-LED-IF was used with both zonal CE separations and
      MEKC. Native fluorescence detection of PAHs was accomplished with detection
      limits ranging from 10 nM to 1.3 microM. Detection limits for OPA/beta-ME-labeled
      glutamic acid and aspartic acid were 11 and 10 nM, respectively, for off-line
      labeling, and 47 and 47 nM, respectively, for on-line labeling, comparable to UV
      laser-based systems. Analysis of OPA/beta-ME-labeled proteins and peptides was
      performed with 28 and 47 nM detection limits for BSA and myoglobin, respectively.

PMID- 16983641
TI  - Carbon nanotube-enhanced separation of DNA fragments by a portable capillary
      electrophoresis system with contactless conductivity detection.
AB  - It was demonstrated that separation of DNA fragments by a CE-contactless
      conductivity detection system (CE-CCD) could be enhanced with multiple-wall
      carbon nanotubes (MWCNs) as buffer additive. For HaeIII digest of PhiX174 DNA,
      optimized MWCN concentration was obtained when the MWCN was above its threshold
      concentration, at which MWCN could form a network in the buffer as
      pseudostationary phase to provide additional interaction sites. In the case of
      larger DNA, MWCN near or below its threshold concentration was enough to provide
      great improvement of the resolution, which was shown by the separation of the 2
      Log DNA ladder. Furthermore, the buffer containing MWCN could provide a more
      stable baseline in the CE-CCD system, owing to less fluctuation of its
      conductivity. Compared with CE-UV, CE-CCD with MWCN could provide lower LODs as
      well as better resolution.

PMID- 16983642
TI  - Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and
      diagnostic laboratory findings.
AB  - The NF2 tumor suppressor gene on chromosome 22 is a member of the protein 4.1
      family of cytoskeletal elements. A number of single- and multiple-tumor
      phenotypes have been linked to alterations of NF2 since its characterization in
      1993. We present a meta-analysis of 967 constitutional and somatic NF2
      alterations from 93 published reports, along with 59 additional unpublished
      events identified in our laboratory and 115 alterations identified in clinical
      samples submitted to the Massachusetts General Hospital (MGH) Neurogenetics DNA
      Diagnostic Laboratory. In total, these sources defined 1,070 small genetic
      changes detected primarily by exon scanning, 42 intragenic changes of one whole
      exon or larger, and 29 whole gene deletions and gross chromosomal rearrangements.
      Constitutional single-exon events (N=422) were significantly more likely to be
      nonsense or splice site changes than somatic events (N=533), which favored
      frameshift changes (chi(2) test; P<0.001). Somatic events also differed markedly
      between tumors of different pathology, most significantly in the tendency of
      somatic events in meningiomas to lie within the 5' FERM domain of the transcript
      (Fisher's exact test; P<0.01 in comparison to schwannomas) with a complete
      absence of mutations in exons 14 and 15. There was no statistically significant
      difference in mutation type or exon distribution between published constitutional
      events and those found by the clinical laboratory. Less than 10% of all published
      and unpublished small alterations are nontruncating (N=63) and these changes are
      clustered in exons 2 and 3, suggesting that this region may be especially crucial
      to tumor suppressor activity in the protein.

PMID- 16983643
TI  - Prenatal GABAB1 and GABAB2 receptors: cellular and subcellular organelle
      localization in early fetal rat cortical neurons.
AB  - Gamma-aminobutyric acid (GABA)(B) receptors appear to influence developmental
      events, depending on whether they are found at a synapse or in extrasynaptic
      areas. Little, if anything, is known as to the cellular and subcellular
      localization of GABA(B1) and GABA(B2) receptors during early fetal development.
      We used Western blots, immunohistochemistry, and postembedding
      immunoelectronmicroscopy to investigate fetal rat brain expression and
      distribution of these receptor proteins. GABA(B1) is expressed as early as
      gestational day (GD) 11.5 and 12.5, with immunoreactivity found in the all
      neuroepithelium, and a high expression in the mantel zone and the cortical area's
      plate; no immunolabeling for GABA(B2) receptor was observed. Our immunogold
      studies define a pattern of early GABA(B1) receptor protein in dendrite
      processes, endoplasmic reticulum, and axon terminals of the cortical
      neuroepithelium on GD 11.5. On GD 12.5, GABA(B1) receptor immunogold was found in
      dendrite processes, spines and tree, axon terminals, mitochondria, and
      intracellular organelles of the cortical neuroepithelium. No synapse formation
      was apparent as no synaptophysin could be found on either GD 11.5 or 12.5. We
      suggest that GABA(B1) has a functional role in the early fetal brain during
      neuronal proliferation and migration, and that it is different from the
      established functional GABA(B) receptor.

PMID- 16983644
TI  - Neuronal differentiation and synapse formation in the space-time with temporal
      fractal dimension.
AB  - An improvement of the Waliszewski and Konarski approach ([2002] Synapse 43:252
      258) to determine the temporal fractal dimension b(t) and scaling factor a(t) for
      the process of neuronal differentiation and synapse formation in the fractal
      space-time is presented. In particular the analytical formulae describing the
      time-dependence of b(t)(t) and a(t)(t), which satisfy the appropriate boundary
      conditions for t-->0 and t-->infinity, are derived. They have been used to
      determine the temporal fractal dimension and scaling factor from the two
      parametric Gompertz function fitted to experimental data obtained by Jones
      Villeneuve et al. ([1982] J Cell Biol 94:253-262) for embryonal carcinoma P19
      cells treated by retinoic acid. The results of the calculations differ from those
      obtained previously by making use of the three- and four-parametric Gompertz
      function as well as other S-shape functions (Chapman, Hill, Logistic, Sigmoid)
      evaluated by the fitting of the experimental curve. The temporal fractal
      dimension can be used as a numerical measure of the neuronal complexity emerging
      in the process of differentiation, which can be related to the morphofunctional
      cell organization. A hypothesis is formulated that neuronal differentiation and
      synapse formation have a lot in common with the process of tumorigenesis. They
      are qualitatively described by the same Gompertz function of growth and take
      place in the fractal space-time whose mean temporal fractal dimension is lost
      during progression.

PMID- 16983645
TI  - Differential effects of chronic amphetamine and baclofen administration on cAMP
      levels and phosphorylation of CREB in distinct brain regions of wild type and
      monoamine oxidase B-deficient mice.
AB  - Roles of GABA(B) transmission were explored in the action of amphetamine (Amph)
      on the brain. Adult male wild type (WT) and monoamine oxidase B-knocked out
      (MAOBKO) mice received i.p. injections of saline, d-Amph (5 mg/kg), plus baclofen
      (GABA(B) receptor agonist, 10 mg/kg), or baclofen and Amph, twice daily for 3
      days and single treatments on day 4, followed by immuno-cyclic-AMP (cAMP) and
      immunoblotting assays on the brain tissue. The WT mice responded with higher
      levels of behavioral responses than the KO to the daily Amph injection; however,
      baclofen blocked the Amph-induced behavioral hyperactivity of both WT and KO
      mice. After the last treatment, levels of cAMP and phosphorylated (p) cyclic-AMP
      response element binding protein (CREB) were up-regulated in the striatum and
      somatosensory cortex of Amph-treated WT mice, while similar to the saline
      controls in the baclofen+Amph-treated group, indicating the blockade by baclofen
      to Amph. Baclofen similarly suppressed the Amph-induced increases in pCREB levels
      of WT hippocampus and amygdala, and decreases of olfactory bulb and thalamus. For
      MAOBKO mice, baclofen hindered the Amph-generated increases in motor cortical
      cAMP and pCREB, and amygdaloid pCREB, and the decrease in olfactory bulb pCREB,
      whereas did not affect the Amph-raised hippocampal pCREB. Furthermore, the levels
      of CREB were variably modified in distinct regions by the drug exposures. The
      data reveal that the GABA(B)-mediated intracellular signaling differentially
      participates in mechanisms underlying Amph perturbation to various regions, and
      may thereby contribute explanations to the behavioral consequences. Moreover,
      MAOB is region-dependently involved in responses of the brain to Amph and
      baclofen, supporting interactions between GABA and monoamines.

PMID- 16983646
TI  - Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule
      transcripts in the prefrontal cortex in schizophrenia.
AB  - Ampakines, positive AMPA receptor modulators, can improve cognitive function in
      schizophrenia, and enhancement of AMPA receptor-mediated currents by them
      potentiates the activity of antipsychotics. In vitro studies have revealed that
      trafficking of AMPA receptors is mediated by specific interactions of a complex
      network of proteins that also target and anchor them at the postsynaptic density
      (PSD). The aim of this study was to determine whether there are abnormalities of
      the molecules associated with trafficking and localization of AMPA receptors at
      the PSD in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. We
      analyzed AMPA receptor expression in DLPFC in schizophrenia, major depression,
      bipolar disorder, and a control group, by examining transcript levels of all four
      AMPA receptor subunits by in situ hybridization. We found decreased GluR2 subunit
      expression in all three illnesses, decreased GluR3 in major depression, and
      decreased GluR4 in schizophrenia. However, autoradiography experiments showed no
      changes in AMPA receptor binding; thus, we hypothesized that these changes in
      receptor subunit stoichiometry do not alter binding to the assembled receptor,
      but rather intracellular processing. In situ hybridization for AMPA-trafficking
      molecules showed decreased expression of PICK1 and increased expression of
      stargazin in DLPFC in schizophrenia, both restricted to large cells of cortical
      layer III. These data suggest that AMPA-mediated glutamatergic neurotransmission
      is compromised in schizophrenia, particularly at the level of AMPA-related PSD
      proteins that mediate AMPA receptor trafficking, synaptic surface expression, and
      intracellular signaling.

PMID- 16983647
TI  - Implication of "Down syndrome cell adhesion molecule" in the hippocampal
      neurogenesis of ischemic monkeys.
AB  - Molecular signals regulating adult neurogenesis in primates are largely unknown.
      Here the authors used differential display to analyze gene expression changes
      that occur in dentate gyrus of adult monkeys after transient global cerebral
      ischemia. Among 14 genes upregulated, the authors focused on Down syndrome cell
      adhesion molecule (DSCAM) known to play crucial role during neuronal development,
      and characterized its expression pattern at the protein level. In contrast with
      approximately threefold upregulation of Dscam gene on days 5 and 7,
      immunoblotting and immunofluorescence analyses using specific antibodies showed a
      gradual decrease of DSCAM after ischemia until day 9 followed by recovery on day
      15. In the control, immunofluorescence reactivity of DSCAM was detected in
      dentate gyrus granule cells and CA4 neurons but decreased after ischemia, being
      compatible with the immunoblotting data. However, in the subgranular zone,
      cerebral ischemia led to a marked increase of DSCAM-positive cells on days 9 and
      15. DSCAM upregulation was seen in two cell types: one is immature neurons
      positive for polysialylated neural cell adhesion molecule or betaIII-tubulin,
      while another is astrocytes positive for S100beta. Young astrocytes were in
      intimate contact with newly generated neurons in the subgranular zone. These data
      suggest implication of DSCAM in the adult neurogenesis of primate hippocampus
      upregulated after ischemia.

PMID- 16983648
TI  - The Italian XLMR bank: a clinical and molecular database.
AB  - Mental retardation (MR) is a nonprogressive condition characterized by a
      significant impairment of intellectual capabilities with deficit of cognitive and
      adaptive functioning and onset before 18 years. Mental retardation occurs in
      about 2 to 3% of the general population and it is estimated that 25 to 35% of the
      cases may be due to genetic causes. Among these "genetic" MR, 25 to 30% are
      probably due to mutations in a gene on the X chromosome (X-linked mental
      retardation, XLMR). Given the genetic heterogeneity of XLMR, the availability of
      a considerable number of patients with accurate phenotypic classification is a
      crucial factor for research. The X-linked Mental Retardation Italian Network,
      which has been active since 2003, has collected detailed clinical information and
      biological samples from a vast number of MR patients. Collected samples and
      clinical information are inserted within the XLMR bank, a comprehensive molecular
      and clinical web-based database available at the address http://xlmr.unisi.it.
      The database is organized in three distinct parts. Part I and II contain several
      electronic schedules to register information on the family, the phenotypic
      description, the photographs, and a 20 sec movie of the patient. Part III allows
      the registration of molecular analyses performed on each case; samples and
      clinical data are usable via password-restricted access. Clinical and molecular
      centers interested in joining the network may request a password by simply
      contacting the Medical Genetics of the University of Siena. The XLMR bank is an
      innovative biological database that allows the collection of molecular and
      clinical data, combines descriptive and iconographic resources, and represents a
      fundamental tool for researchers in the field of mental retardation.

PMID- 16983649
TI  - Asymmetry of neuron numbers in the hippocampal formation of prenatally
      malnourished and normally nourished rats: a stereological investigation.
AB  - There is considerable evidence for lateralization of hippocampal function and
      hemispheric asymmetry in humans. In the rat, studies have reported asymmetries in
      the thicknesses of layers, the volumes of hippocampal subfields, and the density
      of cells at specific points along the septotemporal axis. To determine if there
      is an asymmetry of neuron numbers and whether prenatal malnutrition affects any
      asymmetries, 90-day old male Sprague-Dawley rats that were either normally
      nourished or malnourished prenatally were perfused with 4% paraformaldehyde and
      the brains cut into 30-micro m sections. One interrupted series of sections
      through the entire hippocampus was analyzed stereologically to estimate the total
      number of neurons in the hilus of the dentate gyrus, the CA3/CA2 stratum
      pyramidale (SP), the CA1 SP, and the SP of the prosubiculum/subiculum of both
      hemispheres. Significant asymmetries (P < 0.05) were found in the CA1 and CA3/CA2
      subfields, with the right hemisphere containing 21 and 6% fewer neurons,
      respectively. Malnutrition reduced neuron numbers in the CA1 subfield by 12%, but
      did not alter the hemispheric asymmetry. Our findings agree with previous reports
      of left dominant asymmetries in the rat brain and suggest that this may result
      from differences in total numbers of neurons.

PMID- 16983650
TI  - Synchrotron radiation small angle scattering studies of thermal stability of
      xylanase XYNII from Trichoderma longibrachiatum.
AB  - Xylanase XYNII from Trichoderma longibrachiatum is a small protein of the
      molecular weight 21 kDa, belonging to the family 11 of glycosyl hydrolases, which
      catalyses hydrolysis of xylan. This article reports thermal stability study of
      xylanase XYN II conformation in the temperature range 15-65 degrees C by the
      small angle synchrotron radiation scattering. The study has been performed at
      different pH conditions: at pH 4.0 (below the physiological optimum of the enzyme
      activity) at pH 5.8 close to the optimum for enzymatic activity and at pH 8.0.
      The radius of gyration and the pair distance distribution function p(r) have been
      analyzed to characterize the changes of the enzyme conformation on heating. In
      the environment of the pH close to that of the optimum for the enzymatic
      activity, xylanase shows the greatest thermal stability and undergoes
      denaturation only above 55 degrees C. In the acidic and basic environments, the
      enzyme stability is much lower and denaturation begins at 45 degrees C. On the
      basis of the SAXS data, the shape of the xylanase molecule in solution in
      different temperatures has been reconstructed using ab initio method and program
      DAMMIN. The shape of the xylanase molecule at room temperature is similar to the
      right hand, which is typically observed for xylanase crystal structure. In higher
      temperatures (close to the enzyme activity optimum), the conformation of the
      right hand is loosened and half opened.

PMID- 16983651
TI  - Ligand-DNA interaction in a nanocage of reverse micelle.
AB  - We have studied intercalation of ethidium bromide (EB) to genomic DNA
      encapsulated in a nanospace of an anionic AOT reverse micelle (RM). Circular
      dichroism (CD) study on the DNA in the RM reveals its condensed form. Here, we
      have used temporal decay-associated spectra (DAS) and time-resolved area
      normalized emission spectral (TRANES) techniques to investigate EB-binding to
      condensed DNA because the interference of emission from unbound EB in the RM
      makes conventional steady state and picosecond resolved fluorescence
      spectroscopic techniques challenging. The binding affinity of the ligand EB with
      the DNA in the RM is found to increase with the size of the RM, reflecting the
      effect of lessening of DNA condensation on the binding affinity. CD spectra of
      the DNA in the RM with various sizes indicate the structural change of the
      condensed DNA with reverse micellar size. DAS and TRANES techniques along with
      dynamic light scattering studies of the EB-DNA complex in the RM further reveal
      two kinds of binding modes of the ligand with the condensed DNA even in
      essentially monodispersed RMs. To investigate the role of RM on the ligand
      binding and secondary structure of the DNA, we have also studied complexation of
      EB with two synthetic self-complimentary oligonucleotides of sequences
      (CGCAAATTTGCG)2 and (CGCGCGCGCGCG)2 in the RM.

PMID- 16983652
TI  - A simple combined floating and anchored collagen gel for enhancing mechanical
      strength of culture system.
AB  - In this study, a simple combined method consisting of floating and anchored
      collagen gel in a ligament or tendon equivalent culture system was used to
      produce the oriented fibrils in fibroblast-populated collagen matrices (FPCMs)
      during the remodeling and contraction of the collagen gel. Orientation of the
      collagen fibrils along single axis occurred over the whole area of the floating
      section and most of the fibroblasts were elongated and aligned along the oriented
      collagen fibrils, whereas no significant orientation of fibrils was observed in
      normally contracted FPCMs by the floating method. Higher elasticity and enhanced
      mechanical strength were obtained using our simple method compared with normally
      contracted floating FPCMs. The Young's modulus and the breaking point of the
      FPCMs were dependent on the initial cell densities. This simple method will be
      applied as a convenient bioreactor to study cellular processes of the fibroblasts
      in the tissues with highly oriented fibrils such as ligaments or tendons.

PMID- 16983653
TI  - Biocompatibility evaluation of surface-treated AISI 316L austenitic stainless
      steel in human cell cultures.
AB  - The effects of AISI 316L austenitic stainless steel, tested in untreated state or
      subjected to glow-discharge nitriding (at 10 or 20 hPa) and nitriding + post
      oxidizing treatments, on human umbilical vein endothelial cells (HUVEC) and on
      peripheral blood mononuclear cells (PBMC) were evaluated. All the treated samples
      showed a better corrosion resistance in PBS and higher surface hardness in
      comparison with the untreated alloy. In HUVEC put in contact for 72 h with the
      sample types, proliferation and apoptosis decreased and increased, respectively,
      in the presence of the nitrided + post-oxidized samples, while only slight
      differences in cytokine (TNF-alpha, IL-6, and TGF-beta1) release were registered.
      Intercellular adhesion molecule-1 (ICAM-1) increased in HUVEC incubated with all
      the treated samples, while vascular cell adhesion molecule-1 (VCAM-1) and E
      selectin increased in the presence of all the sample types. PBMC incubated for 48
      h with the samples showed a decrease in proliferation and an increase in
      apoptosis in the presence of the untreated samples and the nitrided + post
      oxidized ones. All the sample types induced a remarkable increase in TNF-alpha
      and IL-6 release in PBMC culture medium, while only the untreated sample and the
      nitrided at 10 hPa induced an increase in ICAM-1 expression. In HUVEC cocultured
      with PBMC, previously put in contact with the treated AISI 316L samples,
      increased levels of ICAM-1 were detected. In HUVEC coincubated with the culture
      medium of PBMC, previously put in contact with the samples under study, a
      noteworthy increase in ICAM-1, VCAM-1, and E-selectin levels was always
      registered, with the exception of VCAM-1, which was not affected by the untreated
      sample. In conclusion, even if the treated samples do not show a marked increase
      in biocompatibility in comparison with the untreated alloy, their higher
      corrosion resistance may suggest a better performance as the contact with
      physiological environment becomes longer.

PMID- 16983654
TI  - Comment to the paper: Enhancing surface free energy and hydrophilicity through
      chemical modification of microstructured titanium implant surfaces, by F. Rupp,
      L. Scheideler, N. Olshanska, M. de Wild, M. Wieland, J. Geis-Gerstorfer.

PMID- 16983655
TI  - Special Populations Networks: themes and lessons learned.
AB  - The Special Populations Networks (SPN) Program was a 5-year, nationwide project
      funded by the National Cancer Institute to reduce cancer-related health
      disparities in minority and other underserved communities by building community
      health infrastructure, improving cancer awareness and use of cancer screening
      services, and increasing the cadre of minority junior scientists studying
      disparities issues. Through collaborations with a wide range of community and
      academic partners, the 18 grantee organizations: 1) developed culturally
      sensitive cancer communications approaches and materials; 2) conducted outreach
      and educational activities appropriate to their communities' needs and diverse
      cultures; and 3) trained and mentored young minority investigators who succeeded
      in winning support for pilot projects addressing local cancer health disparities
      issues, trained and deployed lay health workers, and worked with community and
      health provider organizations to improve understanding of cancer risk in these
      populations and encourage participation in appropriate clinical trials. SPN
      activities were grounded in community-based participatory research principles and
      practice. This overview highlights major project themes, provides examples of
      differing individual grantee approaches to similar issues, and describes key
      lessons learned, as reported by the SPN projects, that may guide future
      programmatic and research efforts to eliminate cancer health disparities in the
      United States. Cancer 2006. Published 2006 by the American Cancer Society.

PMID- 16983657
TI  - New York City's immigrant minorities. Reducing cancer health disparities.
AB  - One million newcomers arrive in the United States every year; 11.7% of the total
      U.S. population is foreign-born. Immigrants face cancer care and research access
      barriers, including economic, immigration status, cultural, and linguistic. In
      2000, the Center for Immigrant Health, NYU School of Medicine, launched the
      Cancer Awareness Network for Immigrant Minority Populations (CANIMP), a network
      comprising community- and faith-based organizations, local and national
      government health institutions, clinical service providers, researchers, and
      immigrant-service and advocacy organizations. This community-based participatory
      program chose as its priorities high- incidence cancer sites in the overall
      immigrant community (colorectal, lung, breast, cervical, prostate), as well as
      sites with strikingly high incidence in specific immigrant groups (gastric,
      liver, oral). CANIMP has developed successful outreach, education, screening,
      survivorship, training, and research programs to decrease cancer disparities.
      Over 2500 at-risk community members have been reached, 25 junior minority
      researchers trained, 60 minority interns mentored, numerous cancer disparities
      research projects funded and conducted, and vital partnerships to improve cancer
      data developed. These initiatives serve as models to address community, systems,
      physician, and cancer research gaps in immigrant communities. Cancer 2006. (c)
      2006 American Cancer Society.

PMID- 16983658
TI  - Neuroprotective effect of N-acetylcysteine on neuronal apoptosis induced by a
      synthetic gingerdione compound: involvement of ERK and p38 phosphorylation.
AB  - Besides being used as a spice, ginger has been applied in oriental medicine to
      ameliorate symptoms such as inflammatory, rheumatic disorders, and
      gastrointestinal discomforts. The effects of ginger on neuronal cells, however,
      have not been explored. We investigate the effect of 1-(3,4-dimethoxyphenyl)-3,5
      dodecenedione (I(6)), a derivative of gingerdione, on cultured cortical neurons.
      After a 5-day maturation period in vitro, cortical neurons were treated with I(6)
      for 24 hr and cell viability was assessed using MTT assay. I(6) induced neuronal
      death in a concentration-dependent manner. Hoechst 33342, propidium iodide (PI),
      and TUNEL staining confirmed that the reduced cell viability by I(6) was due to
      apoptosis. Pre-treatment of cell with N-acetylcysteine (NAC) prevented cell death
      in a concentration-dependent manner. N-acetylcysteine increased phosphorylated
      levels of p42 and p44 extracellular signal-regulated kinases (ERKs). In parallel,
      farnesyltransferase and MEK inhibitors blocked ERK phosphorylation and
      neuroprotective effect of NAC. Unexpectedly, NAC also increased phosphorylated
      level of p38 mitogen-activated protein kinase (MAPK) and p38 specific inhibitors
      dose-dependently attenuated the effect of NAC. Farnesyltransferase and MEK
      inhibitors completely abolished NAC-induced p38 phosphorylation whereas p38
      inhibitor did not influence NAC-induced ERK phosphorylation. These results show
      that NAC serially activates ERKs and p38 MAPK, and ERKs and p38 work together to
      mediate the neuroprotective effect of NAC.

PMID- 16983659
TI  - Striatal specificity of gene expression dysregulation in Huntington's disease.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder caused by
      an expanded CAG repeat region in exon 1 of the HD gene. This mutation results in
      the presence of an abnormally long polyglutamine tract in the encoded protein,
      huntingtin (htt). A major question in this field is how the mutant htt protein,
      which is expressed ubiquitously throughout the brain and body, causes severe
      neuropathologic changes predominantly in the striatum. The mechanisms accounting
      for this specificity are unknown. The role of transcriptional dysregulation in
      the pathophysiology of HD has gained much attention in recent years, however,
      this theory has been unable to explain the specificity of dysfunction and
      degeneration in HD. Microarray studies have showed hundreds of gene expression
      changes in mouse models of HD and in post-mortem brain samples from HD subjects.
      Among the genes whose expression levels are preferentially altered are those that
      exhibit enriched expression in the striatum, which we have argued are the most
      relevant to disease pathology. These "striatal-enriched" genes are associated
      with several systems previously implicated in HD pathology, especially
      disturbances in transcriptional processes and calcium homeostasis. Large-scale
      changes in striatal gene expression in this manner would likely have particularly
      devastating effects to normal striatal function and could explain the specificity
      of striatal dysfunction and ultimate neurodegeneration observed in HD.

PMID- 16983660
TI  - Phosphorylation of glutamate receptors: a potential mechanism for the regulation
      of receptor function and psychostimulant action.
AB  - Ionotropic glutamate receptors, N-methyl-d-aspartate receptors (NMDARs) and alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs), are
      densely distributed in the mammalian brain and actively regulate a variety of
      cellular activities. Expression and function of these receptors are also under a
      tight regulation by many molecular mechanisms. Protein phosphorylation represents
      one of the important mechanisms for the posttranslational modulation of these
      receptors. Constitutive and regulatory phosphorylation occurs at distinct sites
      (serine, threonine, or tyrosine) on the intracellular C-terminal domain of almost
      all subunits capable of assembling a functional channel. Several key protein
      kinases, such as protein kinase A, protein kinase C, Ca(2+)/calmodulin-dependent
      protein kinases, and tyrosine kinases are involved in the site-specific
      catalyzation and regulation of NMDAR and AMPAR phosphorylation. Through the
      phosphorylation mechanism, these protein kinases as well as protein phosphatases
      control biochemical properties (biosynthesis, delivery, and subunit assembling),
      subcellular distribution, and interactions of these receptors with various
      synaptic proteins, which ultimately modify the efficacy and strength of
      excitatory synapses containing NMDARs and AMPARs and many forms of synaptic
      plasticity. Emerging evidence shows that psychostimulants (cocaine and
      amphetamine) are among effective agents that profoundly alter the phosphorylation
      status of both receptors in striatal neurons in vivo. Thus, psychostimulants may
      modulate NMDAR and AMPAR function through the phosphorylation mechanism to shape
      the excitatory synaptic plasticity related to additive properties of drugs of
      abuse.

PMID- 16983661
TI  - pH is an intracellular effector controlling differentiation of oligodendrocyte
      precursors in culture via activation of the ERK1/2 pathway.
AB  - We reported previously that onset of oligodendrocyte precursor cell (OPC)
      differentiation is accompanied by an increase in intracellular pH (pH(i)). We
      show that OPC differentiation is dependent primarily on a permissive pH(i) value.
      The highest differentiation levels were observed for pH(i) values around 7.15 and
      inhibition of differentiation was observed at slightly more acidic or alkaline
      values. Clamping the pH(i) of OPCs at 7.15 caused a transient activation of
      ERK1/2 that was not observed at more acidic or alkaline values. Furthermore,
      inhibition of ERK activation with the UO126 compound totally prevented OPC
      differentiation in response to pH(i) shift. These results indicate that pH(i),
      acting through the ERK1/2 pathway, is a key determinant for oligodendrocyte
      differentiation. We also show that this pH(i) pathway is involved in the process
      of retinoic acid-induced OPC differentiation.

PMID- 16983662
TI  - Morphine upregulates functional expression of neurokinin-1 receptor in neurons.
AB  - Neuronkinin-1 receptor (NK-1R), the neuropeptide substance P (SP) preferring
      receptor, is highly expressed in areas of the central nervous system (CNS) that
      are especially implicated in depression, anxiety, and stress. Repeated exposure
      to opioids may sensitize neuronal systems involved in stress response. We
      examined the effects of morphine, the principal metabolite of heroin, on the
      functional expression of NK-1R in the cortical neurons. NK-1R and mu-opioid
      receptor (MOR) are co-expressed in the cortical neurons. Morphine enhanced NK-1R
      expression in the cortical neurons at both the mRNA and protein levels. The
      upregulated NK-1R by morphine had functional activity, because morphine-treated
      cortical neurons had greater SP-induced Ca(2+) mobilization than untreated
      neurons. Blocking opioid receptors on the cortical neurons by naltrexone or CTAP
      (a mu-opioid receptor antagonist) abolished the morphine action. Investigation of
      the mechanism(s) responsible for the morphine action showed that morphine
      activated NK-1R promoter and induced the phosphorylation of p38 MAPK protein in
      the cortical neurons. These in vitro data provide a plausible cellular mechanism
      for opioid-mediated neurological disorders.

PMID- 16983664
TI  - Excision and transposition of piggyBac transposable element in tobacco budworm
      embryos.
AB  - The TTAA-specific lepidopteran transposon piggyBac has already proved useful as a
      gene-transfer vector for efficient transformation of a wide variety of insects.
      Transposable element excision and transposition assays are useful indicators of
      an element's ability to be mobilized in vivo and, thus, potentially serve as a
      transforming vector. Here, we report that this transposon is capable of excision
      and transposition in tobacco budworm embryos with relatively low frequency.

PMID- 16983663
TI  - Brain-derived neurotrophic factor regulation of N-methyl-D-aspartate receptor
      mediated synaptic currents in suprachiasmatic nucleus neurons.
AB  - Light information reaches the suprachiasmatic nucleus (SCN) through a
      subpopulation of retinal ganglion cells. Previous work raises the possibility
      that brain-derived neurotrophic factor (BDNF) and its high-affinity receptor TrkB
      may be important as modulators of this excitatory input into the SCN. To test
      this possibility, we used whole-cell patch-clamp methods to measure excitatory
      currents in rat SCN neurons. These currents were evoked by electrical stimulation
      of the optic nerve. We found that the amplitude of the N-methyl-D-aspartate
      (NMDA) component of the evoked excitatory postsynaptic currents (NMDA-EPSC) was
      increased by application of BDNF. The neurotrophin also increased the magnitude
      of NMDA-evoked currents in SCN neurons. The BDNF enhancement of the NMDA-EPSC was
      blocked by treatment with the neurotrophin receptor antagonist K252a as well as
      treatment with the soluble form of the TrkB receptor engineered as an
      immunoadhesin (TrkB IgG). Finally, the BDNF enhancement was lost in brain slices
      treated with the NR2B antagonist ifenprodil. The results demonstrate that BDNF
      and TrkB receptors are important regulators of retinal glutamatergic synaptic
      transmission within the SCN.

PMID- 16983665
TI  - Characterization and expression of the Hex 110 gene encoding a glutamine-rich
      hexamerin in the honey bee, Apis mellifera.
AB  - An N-terminal amino acid sequence of a previously reported honey bee hexamerin,
      HEX 110 [Danty et al., Insect Biochem Mol Biol 28:387-397 (1998)], was used as
      reference to identify the predicted genomic sequence in a public GenBank
      database. In silico analysis revealed an ORF of 3,033 nucleotides that
      encompasses eight exons. The conceptual translation product is a glutamine-rich
      polypeptide with a predicted molecular mass of 112.2 kDa and pI of 6.43, which
      contains the conserved M and C hemocyanin domains. Semiquantitative and
      quantitative RT-PCR with specific primers allowed for an analysis of mRNA levels
      during worker bee development and under different physiological conditions.
      Concomitantly, the abundance of the respective polypeptide in the hemolymph was
      examined by SDS-PAGE. Hex 110 transcripts were found in high levels during the
      larval stages, then decreased gradually during the pupal stage, and increased
      again in adults. HEX 110 subunits were highly abundant in larval hemolymph,
      decreased at the spinning-stage, and remained at low levels in pupae and adults.
      In 5th instar larvae, neither starvation nor supplementation of larval food with
      royal jelly changed the Hex 110 transcript levels or the amounts of HEX 110
      subunit in hemolymph. In adult workers, high levels of Hex 110 mRNA, but not of
      the respective subunit, were related to ovary activation, and also to the
      consumption of a pollen-rich diet.

PMID- 16983666
TI  - Effect of juvenile hormone on vitellogenin gene expression in the fat body of
      burying beetles, Nicrophorus orbicollis.
AB  - In the burying beetles, Nicrophorus orbicollis, it is not clear the extent to
      which synthesis of Vitellogenin (Vg) is under hormonal control. Juvenile hormone
      (JH) and ovarian development increase rapidly upon discovery of a carcass, the
      necessary reproductive resource, but in its absence, treatment with JH does not
      accelerate ovarian development. Here we investigated the effect of manipulating
      JH titers on Vg gene expression in the fat bodies of newly eclosed and sexually
      mature females. Topical applications of the JH analogue methoprene at doses of
      200, 300, and 400 microg of methoprene/g beetle to newly eclosed females resulted
      in up to a 5-fold increase in fat body Vg mRNA levels compared to acetone-treated
      control females. However, none of these increases were statistically significant.
      We also measured hemolymph Vg in females subjected to prolonged treatment with an
      intermediate dose of 300 microg of methoprene/g beetle and found no statistically
      significant increase in hemolymph Vg following treatment. There was, however, a
      significantly positive correlation between Vg mRNA and hemolymph Vg. Conversely,
      although injecting sexually mature females with fluvastatin (an inhibitor of JH
      biosynthesis in the corpora allata) at a dose of 40 microg/ beetle resulted in
      significantly decreased JH titers in treated females compared to saline-injected
      controls, Vg transcription rates were not affected. We suggest that in burying
      beetles, JH alone is not sufficient to upregulate the expression of the Vg genes
      and that other factors may be involved in regulating their vitellogenic cycle as
      well.

PMID- 16983667
TI  - Inhibition of EphA7 up-regulation after spinal cord injury reduces apoptosis and
      promotes locomotor recovery.
AB  - Functional impairment after spinal cord injury (SCI) is partially attributed to
      neuronal cell death, with further degeneration caused by the accompanying
      apoptosis of myelin-forming oligodendrocytes. The Eph receptor protein tyrosine
      kinase family and its cognate ligands, the ephrins, have been identified to be
      involved in axonal outgrowth, synapse formation, and target recognition, mainly
      mediated by repulsive activity. Recent reports suggest that ephrin/Eph signaling
      might also play a role as a physiological trigger for apoptosis during embryonic
      development. Here, we investigated the expression profile of EphA7, after SCI, by
      using a combination of quantitative real-time PCR (QRT-PCR) and
      immunohistochemical techniques. QRT-PCR analysis showed an increase in the
      expression of full-length EphA7 at 7 days postinjury (DPI). Receptor
      immunoreactivity was shown mostly in astrocytes of the white matter at the injury
      epicenter. In control animals, EphA7 expression was observed predominantly in
      motor neurons of the ventral gray matter, although some immunoreactivity was seen
      in white matter. Furthermore, blocking the expression of EphA7 after SCI using
      antisense oligonucleotides resulted in significant acceleration of hindlimb
      locomotor recovery at 1 week. This was a transient effect; by 2 weeks postinjury,
      treated animals were not different from controls. Antisense treatment also
      produced a return of nerve conduction, with shorter latencies than in control
      treated animals after transcranial magnetic stimulation. We identified EphA7
      receptors as putative regulators of apoptosis in the acute phase after SCI. These
      results suggest a functional role for EphA7 receptors in the early stages of SCI
      pathophysiology.

PMID- 16983668
TI  - Adipokinetic hormone-induced mobilization of fat body triglyceride stores in
      Manduca sexta: role of TG-lipase and lipid droplets.
AB  - Triglycerides (TG) stores build up in the insect fat body as lipid droplets at
      times of excess of food. The mobilization of fat body triglyceride (TG) is
      stimulated by adipokinetic hormones (AKH). The action of AKH involves a rapid
      activation of cAMP-dependent protein kinase (PKA). Recent in vitro studies have
      shown that PKA phosphorylates and activates the TG-lipase substrate, the lipid
      droplets. Conversely, purified TG-lipase from Manduca sexta fat body is
      phosphorylated by PKA in vitro but is not activated. This study was directed to
      learn whether or not AKH promotes a change in the state of phosphorylation of the
      lipase in vivo, and what are the relative contributions of cytosol and lipid
      droplets to the overall increase of lipolysis triggered by AKH. TG-lipase
      activity of fat body cytosols isolated from control and AKH-treated insects was
      determined against the native substrate, in vivo [3H]-TG radiolabeled lipid
      droplets, obtained from control and AKH-treated insects. The lipase activity of
      the system composed of AKH-cytosol and AKH-lipid droplets (11.1 +/- 2.1 nmol
      TG/min-mg) was 3.1-fold higher than that determined with control cytosol and
      lipid droplets (3.6 +/- 0.5 nmol TG/min-mg). Evaluation of the role of AKH
      induced changes in the lipid droplets on lipolysis showed that changes in the
      lipid droplets are responsible for 70% of the lipolytic response to AKH. The
      remaining 30% appears to be due to AKH-dependent changes in the cytosol. However,
      the phosphorylation level of the TG-lipase was unchanged by AKH, indicating that
      phosphorylation of the TG-lipase plays no role in the activation of lipolysis
      induced by AKH.

PMID- 16983670
TI  - Control of delocalization and structural changes by means of an electric field.
AB  - The strength and, mainly, the direction of a static electric field can be used to
      control delocalization effects occurring in a non-polar pi-system. The
      delocalization energy, the weights, and the probabilities of some local
      electronic structures, the behavior of electron pairs, and the electronic
      fluctuations are considered and examined in cis-butadiene, used as model system.
      The effects of the electric field are detected and evaluated in the basis of
      natural orbital spaces appropriate to investigate the behavior of one- and poly
      electron distributions. The consequences of modifying the delocalization effects
      on structural changes are also investigated. Full geometry optimizations in both
      Hartree-Fock and MP2 levels show that the changes in bond lengths, guided by the
      changes of the behavior of the electronic assembly, can be controlled by means of
      the electric field.

PMID- 16983671
TI  - An iterative knowledge-based scoring function to predict protein-ligand
      interactions: II. Validation of the scoring function.
AB  - We have developed an iterative knowledge-based scoring function (ITScore) to
      describe protein-ligand interactions. Here, we assess ITScore through extensive
      tests on native structure identification, binding affinity prediction, and
      virtual database screening. Specifically, ITScore was first applied to a test set
      of 100 protein-ligand complexes constructed by Wang et al. (J Med Chem 2003, 46,
      2287), and compared with 14 other scoring functions. The results show that
      ITScore yielded a high success rate of 82% on identifying native-like binding
      modes under the criterion of rmsd < or = 2 A for each top-ranked ligand
      conformation. The success rate increased to 98% if the top five conformations
      were considered for each ligand. In the case of binding affinity prediction,
      ITScore also obtained a good correlation for this test set (R = 0.65). Next,
      ITScore was used to predict binding affinities of a second diverse test set of 77
      protein-ligand complexes prepared by Muegge and Martin (J Med Chem 1999, 42,
      791), and compared with four other widely used knowledge-based scoring functions.
      ITScore yielded a high correlation of R2 = 0.65 (or R = 0.81) in the affinity
      prediction. Finally, enrichment tests were performed with ITScore against four
      target proteins using the compound databases constructed by Jacobsson et al. (J
      Med Chem 2003, 46, 5781). The results were compared with those of eight other
      scoring functions. ITScore yielded high enrichments in all four database
      screening tests. ITScore can be easily combined with the existing docking
      programs for the use of structure-based drug design.

PMID- 16983672
TI  - QM/QM study of the coverage effects on the adsorption of amino-cyclopentene at
      the Si(100) surface.
AB  - In this work, we have tested 30 different adsorption situations in several
      coverage scenarios for the 1-amino-3-cyclopentene (ACP) molecule on the Si(100)
      surface. We have used a five-spot testing zone inserted in the high-level part of
      a quantum-mechanical/quantum-mechanical study performed in a big cluster. By
      defining several different scenarios, each one with a typical adsorption energy,
      we were able to understand in detail the process of surface functionalization. We
      are able to justify why the functionalization of this silicon surface achieves
      only a coverage of approximately 0.5 ML (half monolayer) and why the completely
      covered surface should be thermodynamically impossible to obtain.

PMID- 16983673
TI  - An iterative knowledge-based scoring function to predict protein-ligand
      interactions: I. Derivation of interaction potentials.
AB  - Using a novel iterative method, we have developed a knowledge-based scoring
      function (ITScore) to predict protein-ligand interactions. The pair potentials
      for ITScore were derived from a training set of 786 protein-ligand complex
      structures in the Protein Data Bank. Twenty-six atom types were used based on the
      atom type category of the SYBYL software. The iterative method circumvents the
      long-standing reference state problem in the derivation of knowledge-based
      scoring functions. The basic idea is to improve pair potentials by iteration
      until they correctly discriminate experimentally determined binding modes from
      decoy ligand poses for the ligand-protein complexes in the training set. The
      iterative method is efficient and normally converges within 20 iterative steps.
      The scoring function based on the derived potentials was tested on a diverse set
      of 140 protein-ligand complexes for affinity prediction, yielding a high
      correlation coefficient of 0.74. Because ITScore uses SYBYL-defined atom types,
      this scoring function is easy to use for molecular files prepared by SYBYL or
      converted by software such as BABEL.

PMID- 16983674
TI  - A pilot investigation comparing low-energy, double pass 1,450 nm laser treatment
      of acne to conventional single-pass, high-energy treatment.
AB  - BACKGROUND AND OBJECTIVES: Laser treatment using a 1,450 nm diode laser has been
      shown to improve acne and acne scarring. Its widespread adoption in younger
      populations has been significantly limited by discomfort. STUDY DESIGN/MATERIALS
      AND METHODS: Six subjects with active papular acne were treated in a pilot study
      to determine parameters for a split-face, double-pass, low-energy protocol of
      1,450 nm laser treatment. Sides of the face were randomized to receive single
      pass, high-energy treatment (13-14 J/cm(2)), or double-pass, low energy treatment
      (8-11 J/cm(2)), for a total of four treatments delivered at monthly intervals.
      Acne counts and standardized, digital photograph were performed 2 months
      following the final treatment, and compared to pre-treatment counts and
      photographs. RESULTS: Improvement was evaluated comparing pre- and post-treatment
      photos and averaged 2.5 for the high-energy, single-pass side and 2.3 for the low
      energy, double-pass side, using a 0 (worse) to 4 (max improvement) scale. Acne
      counts were reduced 78% on the high-energy, single-pass side and 67% on the low
      energy, double-pass side. Pain ratings on a 1 (min) to 10 (max) scale averaged
      5.6 (range 1-9) for the high-energy, single-pass side and 1.3 (range 1-2) for the
      low-energy, double-pass side. CONCLUSIONS: Low-energy, double-pass 1,450 nm laser
      treatment effectively reduces acne counts 2 months post-treatment, and
      dramatically reduces the pain associated with treatment. The treatment parameters
      used in this study have eliminated the need for anesthetic cream in daily
      practice.

PMID- 16983676
TI  - New transient ischemic attack guidelines: a step forward but journey just begun.

PMID- 16983677
TI  - Characteristics of frontotemporal dementia patients with a Progranulin mutation.
AB  - OBJECTIVE: Mutations in the Progranulin gene (PGRN) recently have been discovered
      to be associated with frontotemporal dementia (FTD) linked to 17q21 without
      identified MAPT mutations. The range of mutations of PGRN that can result in the
      FTD phenotype and the clinical presentation of patients with PGRN mutations have
      yet to be determined. METHODS: In this study, we examined 84 FTD patients from
      families not known previously to have illness linked to chromosome 17 for
      identified PGRN and MAPT mutations and sequenced the coding exons and the
      flanking intronic regions of PGRN. We compared the prevalence, clinical
      characteristics, magnetic resonance imaging and 18-fluoro-deoxyglucose positron
      emission tomography results, and neuropsychological testing of patients with the
      PGRN R493X mutation with those patients without identified PGRN mutations.
      RESULTS: We discovered a new PGRN mutation (R493X) resulting in a stop codon in
      two patients. This was the only PGRN mutation identified in our sample. The
      patients with the PGRN R493X mutation had a rapid illness course and had
      predominant right-sided atrophy and hypometabolism on magnetic resonance imaging
      and 18-fluoro-deoxyglucose positron emission tomography. The affected father of
      one of the patients with the PGRN R493X mutation showed frontal and temporal
      atrophy without neurofibrillary tangles on neuropathological examination.
      INTERPRETATION: Known PGRN and MAPT mutations were rare and of similar prevalence
      in our sample (2 compared with 1/84). The patients with the PGRN R493X mutation
      had a clinical presentation comparable with other behavior-predominant FTD
      patients. The neuropathology of an affected family member of a patient with the
      PGRN R493X mutation appears not to be Alzheimer's disease.

PMID- 16983680
TI  - Frontotemporal dementia, chromosome 17, and progranulin.

PMID- 16983682
TI  - West Nile virus neuroinvasive disease.
AB  - Since 1999, there have been nearly 20,000 cases of confirmed symptomatic West
      Nile virus (WNV) infection in the United States, and it is likely that more than
      1 million people have been infected by the virus. WNV is now the most common
      cause of epidemic viral encephalitis in the United States, and it will likely
      remain an important cause of neurological disease for the foreseeable future.
      Clinical syndromes produced by WNV infection include asymptomatic infection, West
      Nile Fever, and West Nile neuroinvasive disease (WNND). WNND includes syndromes
      of meningitis, encephalitis, and acute flaccid paralysis/poliomyelitis. The
      clinical, laboratory, and diagnostic features of these syndromes are reviewed
      here. Many patients with WNND have normal neuroimaging studies, but abnormalities
      may be present in areas including the basal ganglia, thalamus, cerebellum, and
      brainstem. Cerebrospinal fluid invariably shows a pleocytosis, with a
      predominance of neutrophils in up to half the patients. Diagnosis of WNND depends
      predominantly on demonstration of WNV-specific IgM antibodies in cerebrospinal
      fluid. Recent studies suggest that some WNV-infected patients have persistent WNV
      IgM serum and/or cerebrospinal fluid antibody responses, and this may require
      revision of current serodiagnostic criteria. Although there is no proven therapy
      for WNND, several vaccines and antiviral therapy with antibodies, antisense
      oligonucleotides, and interferon preparations are currently undergoing human
      clinical trials. Recovery from neurological sequelae of WNV infection including
      cognitive deficits and weakness may be prolonged and incomplete.

PMID- 16983683
TI  - Prognostic value of initial magnetic resonance imaging growth rates for World
      Health Organization grade II gliomas.
AB  - A consecutive series of 143 unselected adult patients with histologically proved
      World Health Organization grade II gliomas was reviewed to assess the prognostic
      value of growth rates of mean tumor diameters on successive magnetic resonance
      images before treatment. There is an inverse correlation between growth rates and
      survival (p < 0.001; median survival at 5.16 years for a growth rate of 8mm/year
      or more; median survival >15.0 years for a growth rate <8mm/year). Thus,
      individual magnetic resonance imaging tumor growth rates should be incorporated
      in the planning of the initial therapeutic strategy of grade II gliomas.

PMID- 16983684
TI  - Saving the clinician-scientist: report of the ANA long range planning committee.
AB  - Daunting obstacles to the development of careers in academic medicine represent
      the most important threat to the future of academic neurology. The Long Range
      Planning Committee of the American Neurological Association has for the past 2
      years considered what practical methods might be undertaken to enhance the
      attractiveness of careers as neurologist investigators and to ensure that
      aspiring clinician-scientists are encouraged and retained. The deliberations have
      resulted in several recommendations. First, a plan has been developed to
      introduce flexibility during residency training in neurology. This will permit
      trainees who plan careers in academic medicine to have a substantial exposure to
      research during residency, shortening the subsequent transition to independent
      careers. Second, the American Neurological Association will create an annual
      course in clinical neuroscience research, to be held each summer for academically
      oriented residents. Improved mentoring and career guidance was identified as a
      third priority, addressed in part by the development of several new courses for
      trainees and mentors. Finally, planning is under way for a new postresidency
      training program in clinical research that will link small and large departments
      of neurology. Beyond these recommendations, the entire continuum of training for
      physician-scientists should be reexamined, from the first days of college to the
      successful launch as independent investigators. The development of additional
      demonstration projects to improve the quality and reduce the total length of
      training would be highly desirable.

PMID- 16983686
TI  - Large-scale plant protein subcellular location prediction.
AB  - Current plant genome sequencing projects have called for development of novel and
      powerful high throughput tools for timely annotating the subcellular location of
      uncharacterized plant proteins. In view of this, an ensemble classifier, Plant
      PLoc, formed by fusing many basic individual classifiers, has been developed for
      large-scale subcellular location prediction for plant proteins. Each of the basic
      classifiers was engineered by the K-Nearest Neighbor (KNN) rule. Plant-PLoc
      discriminates plant proteins among the following 11 subcellular locations: (1)
      cell wall, (2) chloroplast, (3) cytoplasm, (4) endoplasmic reticulum, (5)
      extracell, (6) mitochondrion, (7) nucleus, (8) peroxisome, (9) plasma membrane,
      (10) plastid, and (11) vacuole. As a demonstration, predictions were performed on
      a stringent benchmark dataset in which none of the proteins included has > or
      =25% sequence identity to any other in a same subcellular location to avoid the
      homology bias. The overall success rate thus obtained was 32-51% higher than the
      rates obtained by the previous methods on the same benchmark dataset. The essence
      of Plant-PLoc in enhancing the prediction quality and its significance in
      biological applications are discussed. Plant-PLoc is accessible to public as a
      free web-server at: (http://202.120.37.186/bioinf/plant). Furthermore, for public
      convenience, results predicted by Plant-PLoc have been provided in a downloadable
      file at the same website for all plant protein entries in the Swiss-Prot database
      that do not have subcellular location annotations, or are annotated as being
      uncertain. The large-scale results will be updated twice a year to include new
      entries of plant proteins and reflect the continuous development of Plant-PLoc.

PMID- 16983685
TI  - HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive,
      tau-negative inclusions caused by a missense mutation in the signal peptide of
      progranulin.
AB  - OBJECTIVE: Familial autosomal dominant frontotemporal dementia with ubiquitin
      positive, tau-negative inclusions in the brain linked to 17q21-22 recently has
      been reported to carry null mutations in the progranulin gene (PGRN). Hereditary
      dysphasic disinhibition dementia (HDDD) is a frontotemporal dementia with
      prominent changes in behavior and language deficits. A previous study found
      significant linkage to chromosome 17 in a HDDD family (HDDD2), but no mutation in
      the MAPT gene. Longitudinal follow-up has enabled us to identify new cases and to
      further characterize the dementia in this family. The goals of this study were to
      develop research criteria to classify the different clinical expressions of
      dementia observed in this large kindred, to identify the causal mutation in
      affected individuals and correlate this with phenotypic characteristics in this
      pedigree, and to assess the neuropathological characteristics using
      immunohistochemical techniques. METHODS: In this study we describe a detailed
      clinical, pathological and mutation analysis of the HDDD2 kindred. RESULTS:
      Neuropathologically, HDDD2 represents a familial frontotemporal lobar
      degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U). We
      developed research classification criteria and identified three distinct
      diagnostic thresholds, which helped localize the disease locus. The chromosomal
      region with the strongest evidence of linkage lies within the minimum critical
      region for FTLD-U. Sequencing of each exon of the PGRN gene led to the
      identification of a novel missense mutation, Ala-9 Asp, within the signal
      peptide. INTERPRETATION: HDDD2 is an FTLD-U caused by a missense mutation in the
      PGRN gene that cosegregates with the disease and with the disease haplotype in at
      risk individuals. This mutation is the first reported pathogenic missense
      mutation in the signal peptide of the PGRN gene causing FTLD-U. In light of the
      previous reports of null mutations and its position in the gene, two possible
      pathological mechanisms are proposed: (1) the protein may accumulate within the
      endoplasmic reticulum due to inefficient secretion; and (2) mutant RNA may have a
      lower expression because of degradation via nonsense-mediated decay.

PMID- 16983687
TI  - Acetyl-coenzyme A carboxylases: versatile targets for drug discovery.
AB  - Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism
      in humans and most other living organisms. They are attractive targets for drug
      discovery against a variety of human diseases, including diabetes, obesity,
      cancer, and microbial infections. In addition, ACCs from grasses are the targets
      of herbicides that have been in commercial use for more than 20 years.
      Significant progresses in both basic research and in drug discovery have been
      made over the past few years in the studies on these enzymes. At the basic
      research level, the crystal structures of the biotin carboxylase (BC) and the
      carboxyltransferase (CT) components of ACC have been determined, and the
      molecular basis for ACC inhibition by small molecules are beginning to be
      understood. At the drug discovery level, a large number of nanomolar inhibitors
      of mammalian ACCs have been reported and the extent of their therapeutic
      potential is being aggressively explored. This review summarizes these new
      progresses and also offers some prospects in terms of the future directions for
      the studies on these important enzymes.

PMID- 16983688
TI  - 18beta-glycyrrhetinic acid promotes src interaction with connexin43 in rat
      cardiomyocytes.
AB  - The mechanism by which 18beta-glycyrrhetinic acid regulates gap junction
      intercellular communication (GJIC) remains poorly understood. In this study,
      treatment of cultured rat neonatal cardiomyocytes with 18beta-glycyrrhetinic acid
      resulted in dose-dependent inhibition of GJIC as assessed by fluorescent dye
      transfer analysis. 18beta-Glycyrrhetinic acid induced time-dependent
      serine/threonine dephosphorylation and redistribution of connexin43 (Cx43) in
      cardiomyocytes and the induced Cx43 dephosphorylation was prevented by the
      protein phosphatase inhibitor, calyculin A. However, functional analyses showed
      that the inhibitory effect of 18beta-glycyrrhetinic acid on dye spreading among
      cardiomyocytes was not blocked by calyculin A, but was blocked by the Src
      selective tyrosine kinase inhibitor, PP2. 18beta-Glycyrrhetinic acid also induced
      an increase in the levels of phosphorylated Src, and this effect was prevented by
      PP2. Immunoprecipitation using anti-Cx43 and anti-p-Src antibodies showed that
      18beta-glycyrrhetinic acid increased the association between p-Src and Cx43 and
      induced tyrosine phosphorylation of Cx43. We conclude that the inhibitory effect
      of 18beta-glycyrrhetinic acid on GJIC in cardiomyocytes involves Src-mediated
      tyrosine phosphorylation of Cx43.

PMID- 16983689
TI  - Outcome of craniofacial resection in patients 70 years of age and older.
AB  - BACKGROUND: Craniofacial resection (CFR) for patients over 70 years of age is
      uncommon. This study examines a cohort of 36 patients who had CFR at a single
      institution with the aim of reporting mortality, complications, and outcome.
      METHODS: Thirty-six patients 70 years of age and older were identified from a
      prospective database of 234 patients who had CFR at a single institution. The
      median age was 72 years (range, 70-87). Seventeen (47%) patients had had prior
      single-modality or combined treatment, which included surgery in 14 (40%),
      radiation in 13 (36%), and chemotherapy in 2 (6%). Thirty-five patients had a
      malignant tumor and 1 patient a benign tumor; 15 (42%) had high-grade, 17 (47%)
      intermediate-grade, and 4 (11%) low-grade pathology. The margins of resection
      were close or microscopically positive in 18 (50%). Adjuvant radiotherapy was
      given in 15 (42%) and chemotherapy in 1 (3%). Complications were classified into
      overall, local, central nervous system (CNS), systemic, and orbital. Overall
      survival (OS) and disease-specific survival (DSS) were determined using the
      Kaplan-Meier method. Outcomes were compared with patients less than 70 years of
      age. RESULTS: Postoperative mortality occurred in 6 (17%) patients and
      postoperative complications occurred in 23 (64%) patients. Local wound
      complications occurred in 11 (30%), CNS in 12 (33%), systemic in 6 (17%), and
      orbital in 1 (3%). Postoperative mortality and complications were significantly
      higher in patients 70 years of age and older compared with patients less than 70
      years of age (17% versus 1.5%, p = .0005; 64% versus 36%, p = .003,
      respectively). With a median follow-up of 27 months (range, 1-237), the 3 year OS
      and DSS were significantly poorer than patients less than 70 years of age (OS:
      53% versus 69%, p = .0004; DSS: 61% versus 70%, p = .01) due to increased medical
      comorbidity (53% versus 24%, p = .001) and poorer histology (high-, intermediate
      , low-grade histology: 42%, 47%, 11% versus 26%, 47%, 27%, p = .05, respectively)
      in patients over 70 years of age. CONCLUSION: CFR in patients 70 years of age and
      older is associated with increased mortality, increased incidence of
      complications, and a poorer overall and disease-specific 3-year survival,
      compared with patients less than 70 years of age. The survival was likely due to
      increased medical comorbidity and adverse histology. These factors must be taken
      into account when considering an elderly patient for craniofacial resection.

PMID- 16983690
TI  - Propofol lipemia mimicking chyle leak during neck dissection.
AB  - BACKGROUND: Propofol is an intravenous agent used in anesthesia. Lipemia is an
      uncommon adverse effect of propofol infusion. METHODS: A patient undergoing neck
      dissection for recurrent chordoma had intraoperative lipemia develop after
      prolonged propofol infusion. RESULTS: Lipemia gave blood in the surgical field a
      milky appearance resembling chyle, but no chyle leak was present. Lipemia was
      confirmed by drawing a sample of blood and leaving it to stand. Layering of the
      blood with a milky white upper layer was observed. Analysis of a second sample of
      blood revealed a high lipemic index. CONCLUSIONS: Lipemia is an uncommon adverse
      effect of propofol infusion, which may give blood a milky appearance and be
      confused for a chyle leak in a dissected neck. Identification of lipemia is also
      important because there is a risk of acute pancreatitis, and it may represent the
      early stage of propofol infusion syndrome.

PMID- 16983691
TI  - Phase II clinical trial of parenteral hydroxyurea and hyper-fractionated,
      accelerated external beam radiation therapy in patients with advanced squamous
      cell carcinoma of the head and neck: toxicity and efficacy with continuous
      ribonucleoside reductase inhibition.
AB  - BACKGROUND: Almost all concurrent chemoradiation regimens for head and neck are
      platinum based; however, cisplatin is associated with severe renal, oto-, and
      neurotoxicity. Hydroxyurea (HU) has been associated with fewer irreversible
      toxicities. We obtained HU in parenteral form to be administered continually
      during the radiation treatment. Intravenous HU promised better pharmacokinetics
      and cell cycle blockade. METHODS: Participants had biopsy-proven, untreated
      squamous cell carcinoma of the oral cavity, oropharynx (stage IV) and hypopharynx
      (stages II-IV). Radiation therapy consisted initially of 74.4 Gy administered in
      twice daily 1.2-Gy fractions. After 20 patients, the radiation dose was reduced
      to 60.0 Gy, and another 16 patients were enrolled. RESULTS: Patients received HU
      by Continuous Ambulatory Drug Delivery (CADD) pump on a daily x5 schedule during
      radiation therapy. Because of persistent long-term dysphagia, after 20 patients,
      the dose of external beam radiation therapy was reduced from 74 to 60 Gy, and the
      duration of concurrent HU was correspondingly reduced. The new regimen was much
      better tolerated. The median survival for the group as a whole was 30 months.
      Within this small study, there were no significant differences in survival,
      regional control, or local control between the 2 groups. CONCLUSIONS: Lower doses
      of concurrent parenteral HU and hyper-fractionated radiation therapy are
      tolerable and promising.

PMID- 16983692
TI  - Delivery of molecular versus particulate water in spontaneously breathing
      tracheotomized patients.
AB  - BACKGROUND: Adequate humidification of inspired gas with active or passive
      humidifiers is a standard of care for tracheotomized patients. In this study, a
      comparison is made between the tracheal climate after tracheobronchial
      humidification either with molecular water (via a vaporizing humidifier) or
      particulate water (via spray) in spontaneously breathing tracheotomized patients.
      METHODS: We performed a randomized, 2-way crossover study on 10 tracheotomized
      patients. Tracheal humidity and temperature were measured prior to and after use
      of a vaporizing humidifier and aerosol spray, respectively. RESULTS: After use of
      both the vaporizing humidifier and the aerosol spray, the end-inspiratory total
      water content and water gradient in the upper trachea increased significantly,
      compared with baseline values before application. After end of use of the
      vaporizing humidifier, the total water content and the water gradient decreased
      significantly faster than after application of the aerosol spray. CONCLUSIONS:
      Delivery of both molecular and particulate water significantly increases the
      tracheal climate and conditioning in the tracheal airways. Because the tracheal
      humidity remained on a higher level after aerosol spray, we speculate that
      particulate water may be efficient on tracheal humidification for longer.
      However, the positive effect on tracheal humidity after prolonged application of
      the aerosol spray remains to be proven.

PMID- 16983693
TI  - Direct fluorescence visualization of clinically occult high-risk oral
      premalignant disease using a simple hand-held device.
AB  - BACKGROUND: A considerable proportion of oral cancer and precancer is not
      clinically apparent and could contribute significantly to the late diagnosis and
      high mortality of oral cancer. A simple method to identify such occult change is
      needed. METHODS: Patients in the Oral Dysplasia Clinics at British Columbia are
      currently being examined with a simple hand-held device that permits the direct
      visualization of alterations to autofluorescence in the oral cavity. Tissue
      showing loss of autofluorescence is biopsied. RESULTS: We present 3
      representative cases in which occult lesions were identified with fluorescence
      visualization during longitudinal follow-up, resulting in the diagnosis of a
      primary dysplasia in case 1, a second primary cancer in case 2, and cancer
      recurrence in case 3. CONCLUSIONS: This is the first report of the diagnosis of
      occult oral disease using a simple noninvasive device. These early examples
      indicate the potential value of this technology to guide the management of
      patients with oral lesions, facilitating the detection of high-risk changes not
      apparent with white-light visualization.

PMID- 16983694
TI  - Management of complicated head and neck wounds with vacuum-assisted closure
      system.
AB  - BACKGROUND: The vacuum-assisted closure system (V.A.C.), or negative pressure
      dressings, has been successfully used to manage complex wounds of the torso and
      extremities, but its role in the head and neck region has not been frequently
      described. METHODS: A retrospective study was performed. The V.A.C. system
      (Kinetic Concepts Inc., San Antonio, TX) was used at the University of Iowa
      Hospitals and Clinics for management of complicated head and neck wounds.
      RESULTS: The V.A.C. system was utilized at 13 sites for 12 patients. Nine
      subjects had exposed calvarium (4 had failed pedicled reconstructive flaps, 3 had
      ablative or Moh's defects, and 2 had traumatic scalping injuries) necessitating
      bony coverage. Three subjects had the V.A.C. system used as a bolster dressing
      placed over split-thickness skin grafts (STSGs) used to reconstruct large defects
      of the face and skull, and 1 patient had a large soft tissue neck defect after
      radical surgical resection for necrotizing fascitis. One subject used the V.A.C.
      system for the management of 2 distinct wounds. All patients had successful
      healing of their wounds with the V.A.C. system without complication. All STSGs
      had 100% viability after 5 to 7 days of the V.A.C. system use as a bolster
      dressing. CONCLUSION: This study demonstrates the V.A.C. system is a valuable
      tool in the management of complicated head and neck wounds.

PMID- 16983695
TI  - Desmoid tumor of the head and neck.
AB  - BACKGROUND: [corrected] Desmoid tumors are rare benign tumors but have a tendency
      toward local recurrence after resection because of their infiltrative growth and
      frequent entrapment of vital structures in the head and neck region. We report 24
      desmoid tumors of the head and neck and propose a reasonable approach in the
      management of such cases. METHODS: Twenty-four patients (9 male and 15 female;
      median age, 33 years; range, 0-66 years) with a desmoid tumor of the head and
      neck (neck, 15 patients; head, 9 patients) treated from 1990 to 2004 were
      retrospectively analyzed. The size ranged from 0.5 to 13 cm in diameter (mean,
      3.6 cm). In the neck, 8 tumors were around the superficial layer of deep cervical
      fascia, whereas 4 tumors of the neck involved the prevertebral fascia and 2
      involved brachial plexus. RESULTS: Twenty patients received complete resection of
      the tumor, but the section margin was positive in 8 patients, of which 6 patients
      remained free of disease in a period of 13 to 105 months. Three patients,
      including 2 with positive section margin and 1 with negative margin, developed
      recurrences, which were successfully removed again. Two patients underwent
      partial resection of the tumor because of brachial plexus involvement. One of
      them achieved regression after postoperative radiotherapy and the other had
      spontaneous regression. The hypopharygneal tumor in a newborn had spontaneously
      complete regression, and tracheostomy was closed at the age of 6 years. One
      patient remained with stable disease for 14 months after biopsy of the tumor
      without excision. CONCLUSION: The overall prognosis is still good despite
      frequent incomplete resection. Surgical resection of the tumor with close
      observation is suggested even if the section margin is positive. If a desmoid
      tumor cannot be removed grossly, regression or arrested growth of the remaining
      tumor is expected. Radiotherapy might be reserved for a growing tumor.

PMID- 16983696
TI  - Thyroid carcinoma associated with squamous cell carcinoma of the head and neck:
      which policy?
AB  - BACKGROUND: Thyroid carcinoma occurring as a second primary associated with head
      and neck squamous cell carcinoma (HNSCC) is unusual. The clinical management of
      thyroid cancer in such cases has been debated. METHODS: Between 1975 and 2004, we
      collected 33 cases. The associated thyroid carcinoma was diagnosed either during
      or as a consequence of surgery planned as head and neck cancer treatment.
      RESULTS: The associated thyroid carcinoma was never seen to recur. Five-year
      overall survival was 41%. Disease-free survival after 40 and 66 months was 11.1%
      and 5.6%, respectively. CONCLUSIONS: We consider the treatment of thyroid cancer
      to be complete when the thyroid gland, either with or without lymph nodes, has
      been included in the specimen obtained during surgery for HNSCC. In the group of
      cases in which associated thyroid carcinoma was only found within the neck lymph
      nodes and the thyroid gland has not been treated, we discourage further surgical
      treatment or radioactive iodine therapy.

PMID- 16983697
TI  - Comparison of several Nicotiana species as hosts for high-scale Agrobacterium
      mediated transient expression.
AB  - Agrobacterium-mediated transient expression may be regarded as a promising method
      for inexpensive large-scale production of recombinant proteins. We optimized the
      protocol of transient expression in Nicotiana benthamiana and compared six
      Australian species of Nicotiana as hosts for transient expression. The transient
      expression of GFP under 35S CaMV promoter was observed in all species tested,
      although the GFP content in leaves of N. benthamiana, N. exigua, and N. excelsior
      was significantly higher (3.8, 3.7, and 2.0% TSP, respectively). Usage of viral
      based expression system resulted in considerable increase of GFP accumulation in
      N. excelsior and N. benthamiana (63.5 and 16.2% TSP, respectively). We displayed
      that N. excelsior has the best characteristics in regard to biomass yield as well
      as GFP accumulation level for both types of the expression cassettes tested.

PMID- 16983699
TI  - Investigating the in vivo activity of the DeaD protein using protein-protein
      interactions and the translational activity of structured chloramphenicol
      acetyltransferase mRNAs.
AB  - Here, we report the use of an in vivo protein-protein interaction detection
      approach together with focused follow-up experiments to study the function of the
      DeaD protein in Escherichia coli. In this method, functions are assigned to
      proteins based on the interactions they make with others in the living cell. The
      assigned functions are further confirmed using follow-up experiments. The DeaD
      protein has been characterized in vitro as a putative prokaryotic factor required
      for the formation of translation initiation complexes on structured mRNAs.
      Although the RNA helicase activity of DeaD has been demonstrated in vitro, its in
      vivo activity remains controversial. Here, using a method called sequential
      peptide affinity (SPA) tagging, we show that DeaD interacts with certain
      ribosomal proteins as well as a series of other nucleic acid binding proteins.
      Focused follow-up experiments provide evidence for the mRNA helicase activity of
      the DeaD protein complex during translation initiation. DeaD overexpression
      compensates for the reduction of the translation activity caused by a structure
      placed at the initiation region of a chloramphenicol acetyltransferase gene (cat)
      used as a reporter. Deletion of the deaD gene, encoding DeaD, abolishes the
      translation activity of the mRNA with an inhibitory structure at its initiation
      region. Increasing the growth temperature disrupts RNA secondary structures and
      bypasses the DeaD requirement. These observations suggest that DeaD is involved
      in destabilizing mRNA structures during translation initiation. This study also
      provides further confirmation that large-scale protein-protein interaction data
      can be suitable to study protein functions in E. coli.

PMID- 16983701
TI  - Thrombocytosis as a prognostic factor for survival in patients with metastatic
      renal cell carcinoma.
AB  - BACKGROUND: It has been suggested that thrombocytosis, as defined by a platelet
      count >400,000/microL, is a negative predictor for survival among patients with
      metastatic renal cell carcinoma. However, this has not been a uniform finding.
      METHODS: To address this issue, retrospective analysis of 700 previously
      untreated patients entering on institution review board-approved phase 1, 2, or 3
      clinical trials in the United States and Europe was conducted between 1982 and
      2002. RESULTS: Thrombocytosis was present at study entry in 25% of patients.
      Median baseline platelet count was 304,000/microL (range, 86-1,420,000/microL).
      Eighty-seven percent of patients died with a median survival of 13.0 months.
      Median follow-up for patients not known to have died was 2.4 years. On univariate
      analysis, patients with elevated platelet counts had significantly shorter
      survival than patients with normal platelet counts; median survivals of 8.4 and
      14.6 months, respectively, P < .001. However, platelet count was associated with
      several clinical and biochemical factors, including gender, age, performance
      status, time from diagnosis to study entry, prior radiotherapy or nephrectomy,
      presence of liver metastasis, number of metastatic sites, amount of hemoglobin,
      white blood cell count, amount of lactate dehydrogenase, and amount of serum
      alkaline phosphatase. Several of these factors have previously been reported as
      prognostic indicators for survival, and, therefore, multivariable analyses were
      conducted to determine whether thrombocytosis is an independent predictor of
      survival. After adjusting for multiple factors, thrombocytosis continued to
      impact negatively on survival, P < .001. CONCLUSIONS: Thrombocytosis was found to
      be an independent prognostic factor for survival in patients with metastatic
      renal cell carcinoma.

PMID- 16983702
TI  - Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates
      with survival in ovarian cancer.
AB  - BACKGROUND: Growth factor receptors and cell signaling factors play a crucial
      role in human carcinomas and have been studied in ovarian tumors with varying
      results. Cell signaling involves multiple pathways and a myriad of factors that
      can be mutated or amplified. Cell signaling is driven through the mammalian
      target of rapamycin (mTOR) and extracellular regulated kinase (ERK) pathways and
      by some downstream molecules, such as 4E binding protein 1 (4EBP1), eukaryotic
      initiation factor 4E, and p70 ribosomal protein S6 kinase (p70S6K). The
      objectives of this study were to analyze the real role that these pathways play
      in ovarian cancer, to correlate them with clinicopathologic characteristics, and
      to identify the factors that transmit individual proliferation signals and are
      associated with pathologic grade and prognosis, regardless specific oncogenic
      alterations upstream. METHODS: One hundred twenty-nine ovarian epithelial tumors
      were studied, including 20 serous cystadenomas, 7 mucinous cystadenomas, 11
      serous borderline tumors, 16 mucinous borderline tumors, 29 serous carcinomas, 16
      endometrioid carcinomas, 15 clear cell carcinomas, and 15 mucinous carcinomas.
      Tissue microarrays were constructed, and immunohistochemistry for the receptors
      epidermal growth factor receptor (EGFR) and c-erb-B2 was performed and with
      phosphorylated antibodies for protein kinase B (AKT), 4EBP1, p70S6K, S6, and ERK.
      RESULTS: Among 129 ovarian neoplasms, 17.8% were positive for c-erb-B2, 9.3% were
      positive for EGFR, 47.3% were positive for phosphorylated AKT (p-AKT), 58.9% were
      positive for p-ERK, 41.1% were positive for p-4EBP1, 26.4% were positive for
      p70S6K, and 15.5% were positive for p-S6. Although EGFR, p-AKT, and p-ERK
      expression did not differ between benign, borderline, or malignant tumors, c-erb
      B2, p-4EBP1, p-p70S6K, and p-S6 were expressed significantly more often in
      malignant tumors. Only p-4EBP1 expression demonstrated prognostic significance (P
      = .005), and only surgical stage and p-4EBP1 expression had statistical
      significance in the multivariate analysis. CONCLUSIONS: In patients with ovarian
      carcinoma, significant expression of p-4EBP1 was associated with high-grade
      tumors and a poor prognosis, regardless other oncogenic alterations upstream.
      This finding supports the study of this factor as a hallmark or pivotal factor in
      cell signaling in ovarian carcinoma that may crucial in the transmission of the
      proliferation cell signal and may reflect the real oncogenic role of this pathway
      in ovarian tumors.

PMID- 16983703
TI  - Analysis of differential BRAF(V600E) mutational status in multifocal papillary
      thyroid carcinoma: evidence of independent clonal origin in distinct tumor foci.
AB  - BACKGROUND: Papillary thyroid cancers often occur as multiple foci. Multifocal
      cancers have been considered to have a poor prognosis because they are thought to
      be the consequence of intrathyroidal spread of the papillary cancer. However, to
      the authors' knowledge there has been little investigation into whether
      multifocal thyroid papillary carcinomas arise from the intrathyroidal spread of a
      single carcinoma or from independent primary tumors. To answer this question, the
      BRAF(V600E) mutational status of individual tumor foci was examined. This
      approach was justified because in the Korean population a high proportion (65%)
      of papillary carcinomas harbor the BRAF mutation. METHODS: DNA was isolated from
      paraffin-embedded tissue samples of multifocal papillary thyroid carcinoma and
      the BRAF exon 15 was amplified by the polymerase chain reaction (PCR). The PCR
      product was digested with restriction endonuclease TspRI to test for the presence
      of the BRAF(V600E) (T1799A) mutation. RESULTS: In all, 140 cancers from 61
      patients diagnosed with multifocal papillary carcinoma were examined. The BRAF
      mutation was found in all the individual cancers in 29 (47.5%) of the patients
      (all-positive group) and the mutation was absent in all the individual cancers in
      8 (13.1%) patients (all-negative group). However, in 24 (39.3%) patients, some of
      the individual cancers contained the BRAF mutation, whereas others did not (mixed
      group). CONCLUSIONS: At least 39.3% of the multifocal papillary cancers in the
      Korean population that were examined could be attributed to independently arising
      papillary cancers rather than to intrathyroidal spread of single cancers.

PMID- 16983704
TI  - Expression of inhibitor of apoptosis proteins in B-cell non-Hodgkin and Hodgkin
      lymphomas.
AB  - BACKGROUND: Inhibitor of apoptosis proteins (IAPs) inhibit apoptosis by binding
      specific caspases, and possibly by other mechanisms. Eight IAPs have been
      identified in humans, of which cIAP1, cIAP2, and XIAP are well known. IAPs are
      being investigated as potential treatment targets in cancer patients. METHODS:
      cIAP1, cIAP2, and XIAP were assessed in lymphoma cell lines, 240 B-cell non
      Hodgkin lymphoma (NHL) tumors, and 40 Hodgkin lymphoma (HL) tumors. RESULTS: All
      IAPs were expressed in most NHL and all HL cell lines. In NHL tumors, cIAP1 was
      expressed in 174 (73%), cIAP2 in 115 (48%), and XIAP in 37 (15%). cIAP1 was
      positive in all precursor B-cell lymphoblastic lymphoma/leukemia (LBL) and nodal
      marginal zone B-cell lymphoma (MZL), over 90% of follicular lymphoma and diffuse
      large B-cell lymphoma (DLBCL), and approximately 50% to 60% of myeloma, Burkitt
      lymphoma (BL), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM),
      small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL), extranodal
      marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT
      lymphoma), splenic MZL, and mantle cell lymphoma. cIAP2 was positive in all MALT
      lymphoma, over 90% of precursor B-cell LBL (94%), most BL (75%), LPL/WM (71%),
      and SLL/CLL (67%), and approximately 40% to 60% of follicular lymphoma, myeloma,
      and DLBCL. XIAP was positive most cases of precursor B-cell LBL (57%) and
      approximately 30% to 40% of nodal MZL, BL, and DLBCL. In HL tumors, cIAP1 was
      positive in 30 (75%), cIAP2 in 27 (68%), and XIAP in 23 (58%), and did not
      correlate with histologic type. CONCLUSIONS: Differential expression of IAPs in B
      cell lymphomas suggests differences in pathogenesis that may have implications
      for novel treatment strategies targeting IAPs.

PMID- 16983705
TI  - Potential diagnostic value of methylation profile in pleural fluid and serum from
      cancer patients with pleural effusion.
AB  - BACKGROUND: The objective of this study was to investigate the diagnostic value
      of methylation profiles for discrimination between malignant and benign pleural
      effusions. A secondary objective was to examine the concordance of methylation in
      samples of serum and pleural fluid. METHODS: The authors used methylation
      specific polymerase chain reaction (MSP) analysis to examine the promoter
      methylation status of 4 genes in patients with pleural effusion: death-associated
      protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid
      receptor beta (RARbeta), and p16/INK4a. Pleural effusions were collected from 87
      patients who had their diagnoses confirmed on cytologic and/or histologic
      examinations and clinical evolution. Pleural effusions were classified as
      malignant (n = 53 patients) or benign (n = 34 patients). RESULTS: Methylation was
      detected in serum from 45.3% of patients with malignant pleural effusions and
      from 0% of patients with benign pleural effusions, and it was detected in pleural
      fluid samples from 58.5% of patients with malignant pleural effusions and from 0%
      of patients with benign pleural effusions (P = .001). The sensitivity of MSP was
      greater than that of cytologic examination alone (39.1%; P = .001). When MSP was
      used together with cytologic examination, sensitivity increased to 69.8% (P =
      .001). CONCLUSIONS: Cell-free methylated DNA in pleural fluid can be detected in
      patients with neoplastic malignancy in a single extraction by thoracocentesis.
      Adequate management of the extracted pleural fluid can provide a rapid and
      reliable diagnosis in patients with pleural effusions who have suspected
      malignancy. MSP, used together with cytologic examination, may obviate the need
      for other invasive diagnostic tests.

PMID- 16983706
TI  - Investigation of guanosine-quartet assemblies by vibrational and electronic
      circular dichroism spectroscopy, a novel approach for studying supramolecular
      entities.
AB  - The self-assembly of guanosine-5'-hydrazide G-1 in D(2)O, in the presence and
      absence of sodium cations, has been investigated by chiroptical techniques:
      electronic (ECD) and the newly introduced vibrational (VCD) circular dichroism
      spectroscopy. Using a combination of ECD and VCD with other methods such as IR,
      electron microscopy, and electrospray ionization mass spectrometry (ESI-MS) it
      was found that G-1 produces long-range chiral aggregates consisting of G
      quartets, (G-1)(4), subsequently stacked into columns, [(G-1)(4)](n), induced by
      binding of metal cations between the (G-1)(4) species. This process, accompanied
      by gelation of the sample, is highly efficient in the presence of an excess of
      sodium cations, leading to aggregates with strong quartet-quartet interaction.
      Thermally induced conformational changes and conformational stability of
      guanosine-5'-hydrazide assemblies were studied by chiroptical techniques and the
      melting temperature of the hydrogels formed was obtained. The temperature
      dependent experiments indicate that the long-range supramolecular aggregates are
      dissociated by increasing temperature into less ordered species, monomers, or
      other intermediates in equilibrium, as indicated by MS experiments.

PMID- 16983707
TI  - Olefin epoxidation with hydrogen peroxide catalyzed by lacunary polyoxometalate
      [gamma-SiW10O34H2O2]4-.
AB  - The tetra-n-butylammonium (TBA) salt of the divacant Keggin-type polyoxometalate
      [TBA](4)[gamma-SiW(10)O(34)(H(2)O)(2)] (I) catalyzes the oxygen-transfer
      reactions of olefins, allylic alcohols, and sulfides with 30 % aqueous hydrogen
      peroxide. The negative Hammett rho(+) (-0.99) for the competitive oxidation of p
      substituted styrenes and the low value of (nucleophilic oxidation)/(total
      oxidation), X(SO)=0.04, for I-catalyzed oxidation of thianthrene 5-oxide (SSO)
      reveals that a strongly electrophilic oxidant species is formed on I. The
      preferential formation of trans-epoxide during epoxidation of 3-methyl-1
      cyclohexene demonstrates the steric constraints of the active site of I. The I
      catalyzed epoxidation proceeds with an induction period that disappears upon
      treatment of I with hydrogen peroxide. (29)Si and (183)W NMR spectroscopy and CSI
      mass spectrometry show that reaction of I with excess hydrogen peroxide leads to
      fast formation of a diperoxo species, [TBA](4)[gamma-SiW(10)O(32)(O(2))(2)] (II),
      with retention of a gamma-Keggin type structure. Whereas the isolated compound II
      is inactive for stoichiometric epoxidation of cyclooctene, epoxidation with II
      does proceed in the presence of hydrogen peroxide. The reaction of II with
      hydrogen peroxide would form a reactive species (III), and this step corresponds
      to the induction period observed in the catalytic epoxidation. The steric and
      electronic characters of III are the same as those for the catalytic epoxidation
      by I. Kinetic, spectroscopic, and mechanistic investigations show that the
      present epoxidation proceeds via III.

PMID- 16983708
TI  - Diversity-oriented approach to biologically relevant molecular frameworks
      starting with beta-naphthol and using the Claisen rearrangement and olefin
      metathesis as key steps.
AB  - A diversity-oriented approach for the synthesis of various structurally different
      molecular frameworks from readily accessible and common precursors is described.
      A Claisen rearrangement followed by ring-closing metathesis or ethylene-promoted
      ring-closing enyne metathesis has been utilized as the key synthetic
      transformation to generate naphthoxepine derivatives. The ring-closing metathesis
      approach has also been used to generate spirocyclic compounds and the pleiadene
      framework.

PMID- 16983709
TI  - Metal-salen-base-pair complexes inside DNA: complexation overrides sequence
      information.
AB  - Two isomeric salicylic aldehyde nucleobases have been prepared and incorporated
      into various DNA duplexes. Reaction with ethylenediamine leads to formation of
      the well-known salen ligand inside the DNA double helix. Addition of transition
      metal ions such as Cu(2+), Mn(2+), Ni(2+), Fe(2+), or VO(2+) results in the
      formation of metal-salen-base-pair complexes, which were studied by using UV and
      circular dichroism (CD) spectroscopy. HPLC and ESI mass spectrometric
      measurements reveal an unusually high stability of the DNA-metal system. These
      metal-salen complexes act as interstrand cross-links and thereby lead to a strong
      stabilization of the DNA duplexes, as studied by thermal de- and renaturing
      experiments. Complex formation is strong enough to override sequence information
      even when the preorganization of the ligand precursors is unfavorable and the DNA
      duplex is distorted by the metal complexation. Furthermore, melting-point studies
      show that the salen complex derived from ligand 2 fits better into the DNA
      duplex, in accordance with results obtained from the crystal structure of the
      corresponding copper-salen complex 8.

PMID- 16983710
TI  - A ring-fusion/ring-fission mechanism for the metathesis reaction of macrocyclic
      formaldehyde acetals.
AB  - Important insight has been obtained into the mechanism of the reversible acid
      catalysed transacetalation of cyclophane formaldehyde acetals (formals) C(i) in
      CDCl(3), at 25 degrees C. The order of appearance of the lowest oligomers in the
      early stages of the equilibration reaction is fully consistent with ring
      fusion/ring-fission processes in which oxonium ion intermediates undergo S(N)2
      reactions, according to an acid-catalysed bimolecular (A2) mechanism. The
      alternative acid-catalysed monomolecular (A1) reaction path, based on "back
      biting" processes of carbenium ions generated by S(N)1-type cleavage of oxonium
      ion intermediates, predicts sequences that are in marked contrast with
      experimental findings.

PMID- 16983711
TI  - p53--a natural cancer killer: structural insights and therapeutic concepts.
AB  - Every single day, the DNA of each cell in the human body is mutated thousands of
      times, even in absence of oncogenes or extreme radiation. Many of these mutations
      could lead to cancer and, finally, death. To fight this, multicellular organisms
      have evolved an efficient control system with the tumor-suppressor protein p53 as
      the central element. An intact p53 network ensures that DNA damage is detected
      early on. The importance of p53 for preventing cancer is highlighted by the fact
      that p53 is inactivated in more than 50 % of all human tumors. Thus, for good
      reason, p53 is one of the most intensively studied proteins. Despite the great
      effort that has been made to characterize this protein, the complex function and
      the structural properties of p53 are still only partially known. This review
      highlights basic concepts and recent progress in understanding the structure and
      regulation of p53, focusing on emerging new mechanistic and therapeutic concepts.

PMID- 16983712
TI  - Double-faced micelles from water-soluble polymers.

PMID- 16983713
TI  - Direct identification of tryptophan in a mixture of amino acids by the naked eye.

PMID- 16983714
TI  - Suitanes.

PMID- 16983715
TI  - An anticoagulant with light-triggered antidote activity.

PMID- 16983716
TI  - Computationally-assisted approach to the vibrational spectra of molecular
      crystals: study of hydrogen-bonding and pseudo-polymorphism.
AB  - A new computationally-assisted methodology (PiMM), which accounts for the effects
      of intermolecular interactions in the crystal, is applied to the complete
      assignment of the Raman and infrared vibrational spectra of room temperature
      forms of crystalline caffeine, theobromine, and theophylline. The vibrational
      shifts due to crystal packing interactions are evaluated from ab initio
      calculations for a set of suitable molecular pairs, using the B3LYP/6-31G*
      approach. The proposed methodology provides an answer to the current demand for a
      reliable assignment of the vibrational spectra of these methyl-xanthines, and
      clarifies several misleading assignments. The most relevant intermolecular
      interactions in each system and their effect on the vibrational spectra are
      considered and discussed. Based on these results, significant insights are
      obtained for the structure of caffeine in the anhydrous form (stable at room
      temperature), for which no X-ray structure has been reported. A possible
      structure based on C((8))--H...N((9)) and C((1,3))--H...O intermolecular
      interactions is suggested.

PMID- 16983717
TI  - Cooperative interactions in supramolecular aggregates: linear and nonlinear
      responses in calix[4]arenes.
AB  - The linear and nonlinear optical polarizabilities of donor-acceptor (D-pi-A)
      chromophores in confined geometries of calix[4]arenes are investigated through a
      model for interacting polar-polarizable molecules. Both the linear polarizability
      (alpha) and the first hyperpolarizability (beta) decrease with increasing the
      interdipolar angle, as expected in the oriented-gas picture. However, within the
      polar-polarizable model we predict deviations from the additive result,
      irrespective of the interdipolar angle. Depending on the nature of the
      chromophore, electrostatic intermolecular interactions between polar and
      polarizable chromophores lead to cooperative damping or enhancement of the
      optical responses. Specifically, for chromophores whose ground state is dominated
      by the neutral D-pi-A structure both alpha and beta are suppressed with respect
      to the prediction of the oriented-gas model, whereas the opposite holds true for
      chromophores whose ground state is dominated by the zwitterionic D(+)-pi-A(-).
      These results explain recent experimental data on a calix[4]arene functionalized
      with a donor-acceptor dye for nonlinear optical applications. Density functional
      theory calculations on the relevant crystal structure further support our
      interpretation.

PMID- 16983718
TI  - Carbohydrates as scaffolds in drug discovery.
AB  - Drug discovery has long suffered from the difficulty of having to place
      pharmacophoric groups in just the right spatial arrangement to elicit the desired
      biological response. Although some molecule classes have been discovered that
      seem to be privileged structures for at least some drug-receptor interactions,
      there remains the challenge to design and synthesize molecules with high specific
      affinity to pharmacologically important targets. With their high density of
      stereochemical information and their relative rigidity, carbohydrates provide
      excellent platforms upon which to display a number of substituents in a
      sterically defined way, hence offering the opportunity to harness their unique
      features for the drug-discovery process. This review highlights the progress that
      has been made in the development of carbohydrate scaffolds for drug discovery.

PMID- 16983719
TI  - Transmembrane TNF protects mutant mice against intracellular bacterial
      infections, chronic inflammation and autoimmunity.
AB  - Using targeted mutagenesis in mice, we have blocked shedding of endogenous murine
      TNF by deleting its cleavage site. Mutant mice produce physiologically regulated
      levels of transmembrane TNF (tmTNF), which suffice to support thymocyte
      proliferation but cannot substitute for the hepatotoxic activities of wild-type
      TNF following LPS/D-galactosamine challenge in vivo and are not sufficient to
      support secondary lymphoid organ structure and function. Notably, however, tmTNF
      is capable of exerting anti-Listerial host defenses while remaining inadequate to
      mediate arthritogenic functions, as tested in the tristetraprolin-deficient model
      of TNF-dependent arthritis. Most interestingly, in the EAE model of autoimmune
      demyelination, tmTNF suppresses disease onset and progression and retains the
      autoimmune suppressive properties of wild-type TNF. Together, these results
      indicate that tmTNF preserves a subset of the beneficial activities of TNF while
      lacking detrimental effects. These data support the hypothesis that selective
      targeting of soluble TNF may offer several advantages over complete blockade of
      TNF in the treatment of chronic inflammation and autoimmunity.

PMID- 16983720
TI  - Cell death and thymic export during fetal life.
AB  - In the fetus the peripheral T cell pool expands as the fetus grows, but the
      mechanisms that regulate T cell homeostasis during fetal life are unknown. Here,
      we show that the peripheral T cell pool in the sheep fetus is established by the
      export from the fetal thymus of twice as many CD8+ as CD4+ thymic emigrants every
      day. Clonal deletion of CD4+ thymocytes in the fetal thymus appeared to be more
      stringent than was the case for CD8+ thymocytes because only 1 in 35 single
      positive CD4 (SPCD4) thymocytes was exported from the thymus whereas the majority
      (2/3) of the single-positive CD8 (SPCD8) thymocytes were exported from the fetal
      thymus each day. Furthermore, within the thymus, the number of apoptotic SPCD4
      thymocytes was 40 times greater than the number of apoptotic SPCD8 thymocytes. A
      tissue-specific migration of CD8+ emigrants localizing in the spleen was also
      established in the fetus in contrast to CD4+ emigrants, which migrated randomly
      to spleen and LN.

PMID- 16983721
TI  - Membrane-bound eotaxin-3 mediates eosinophil transepithelial migration in IL-4
      stimulated epithelial cells.
AB  - Epithelial cells play an important role in orchestrating mucosal immune
      responses. In allergic-type inflammation, epithelial cells control the
      recruitment of eosinophils into the mucosa. Th2-type cytokine-driven release of
      eosinophil-active chemokines from epithelial cells directs eosinophil migration
      into the mucosal epithelium. CCR3, the main eosinophil chemokine receptor,
      regulates this process; however, the respective contribution of individual CCR3
      ligands in eosinophil transepithelial migration is less well understood. Using an
      in vitro transepithelial chemotaxis system, we found that eotaxin-3 produced by
      IL-4-stimulated airway epithelial cells and CCR3 on eosinophils exclusively
      mediate eosinophil transepithelial migration. Eotaxin-3 protein levels were also
      increased in the nasal mucosal epithelium recovered from allergic patients as
      compared to non-allergic patients. Surprisingly, eotaxin-3 in IL-4-stimulated
      airway epithelial cells was predominantly cell surface bound, and the cell
      surface form was critical for eosinophil transepithelial migration. Eotaxin-3
      cell surface association was partially glycosaminoglycan (GAG) dependent, but was
      completely protein dependent, suggesting that eotaxin-3 associates with both GAG
      and cell surface proteins. We thus provide evidence that cell surface-associated
      eotaxin-3 is the critical IL-4-dependent chemotactic signal mediating eosinophil
      transepithelial migration in the setting of allergic inflammation.

PMID- 16983722
TI  - Peripheral B cell receptor editing may promote the production of high-affinity
      autoantibodies in CD22-deficient mice.
AB  - CD22-deficient mice are characterized by B cell hyperactivity and autoimmunity.
      We have constructed knock-in CD22-/- mice, expressing an anti-DNA heavy (H) chain
      (D42), alone or combined with Vkappa1-Jkappa1 or Vkappa8-Jkappa5 light (L)
      chains. The Ig-targeted mice produced a lupus-like serology that was age- and sex
      dependent. High-affinity IgG autoantibodies were largely dependent on the
      selection of B cells with a particular H/L combination, in which a non
      transgenic, endogenous L chain was assembled by secondary rearrangements through
      the mechanism of receptor editing. Moreover, we present evidence that these
      secondary rearrangements are very prominent in splenic peripheral B cells. Since
      CD22 is primarily expressed on the surface of peripheral B cells, we propose a
      model for the development of a lupus-like autoimmune disease by a combination of
      peripheral receptor editing and abnormal B cell activation.

PMID- 16983723
TI  - Maintenance of CCL5 mRNA stores by post-effector and memory CD8 T cells is
      dependent on transcription and is coupled to increased mRNA stability.
AB  - Immunological memory is associated with the display of improved effector
      functions by cells of the adaptive immune system. The storage of untranslated
      mRNA coding for the CCL5 chemokine by CD8 memory cells is a new process
      supporting the immediate display of an effector function. Here, we show that,
      after induction during the primary response, high CCL5 mRNA levels are
      specifically preserved in CD8 T cells. We have investigated the mechanisms
      involved in the long-term maintenance of CCL5 mRNA levels by memory CD8 T cells.
      We demonstrate that the CCL5 mRNA half-life is increased in memory CD8 T cells
      and that these cells constitutively transcribe ccl5 gene. By inhibiting ccl5
      transcription using IL-4, we demonstrate the essential role of transcription in
      the maintenance of CCL5 mRNA stores. Finally, we show that these stores are
      spontaneously reconstituted when the inhibitory signal is removed, indicating
      that the transcription of ccl5 is a default feature of memory CD8 T cells
      imprinted in their genetic program.

PMID- 16983724
TI  - A distinct subset of intestinal dendritic cells responds selectively to oral
      TLR7/8 stimulation.
AB  - The intestinal innate immune system continually interacts with commensal
      bacteria, thus oral vaccines should induce extra/alternative activation of DC,
      potentially through TLR. To examine this we collected intestinal lymph DC (iL-DC)
      under steady-state conditions and after feeding resiquimod (R-848), a synthetic
      TLR7/8 ligand, which we showed induces complete emptying of gut DC into lymph. iL
      DC are heterogeneous with subset-specific functions. In this study we determined
      the kinetics of iL-DC subset release, activation and cytokine secretion induced
      by R-848. We show that L-DC comprise three distinct subsets (CD172ahigh,
      CD172aint and CD172alow) present with similar frequencies in intestinal but not
      hepatic lymph. No iL-DC express TLR7 mRNA, and only CD172a+ iL-DC express TLR8.
      However, after oral R-848 administration, output of all three subsets increases
      dramatically. CD172ahigh DC release precedes that of CD172alow DC, and the
      increased frequency of CD25high iL-DC is restricted to the two CD172a+ subsets.
      After feeding R-848 only CD172ahigh iL-DC secrete IL-6 and IL-12p40. However,
      CD172aint and CD172ahigh DC secrete similar but markedly lower amounts when
      stimulated in vitro. These results highlight the importance of in vivo approaches
      to assess adjuvant effects on DC and give novel insights into the subset-specific
      effects of an oral TLR ligand on intestinal DC.

PMID- 16983726
TI  - Intrinsic dinitrogen activation at bare metal atoms.
AB  - There is ongoing interest in metal complexes which bind dinitrogen and facilitate
      either its reduction or oxidation under mild conditions. In nature, the enzyme
      nitrogenase catalyzes this process, and dinitrogen fixation occurs under mild and
      ambient conditions at a metal-sulfur cluster in the center of the MoFe protein,
      but the mechanism of this process remains largely unknown. In the last few years,
      new important discoveries have been made in this field. In this review are
      discussed recent findings on the interaction of N(2) with metal atoms and metal
      atom dimers from all groups of the periodic table as provided by gas-phase as
      well as matrix-isolation experiments. Intrinsic dinitrogen activation at such
      bare metal atoms is then related to corresponding processes at complexes,
      clusters, and surfaces.

PMID- 16983725
TI  - The role of CD69 in acute neutrophil-mediated inflammation.
AB  - The leukocyte activation marker CD69 functions as a negative regulator of the
      immune response, both in NK-dependent tumor rejection and in the inflammation
      associated with lymphocyte-dependent collagen-induced arthritis. In contrast, it
      has been reported that CD69-deficient mice are refractory to the neutrophil
      dependent acute inflammatory response associated with anti-type II collagen
      antibody-induced arthritis (CAIA), suggesting a positive regulatory role for CD69
      in neutrophil function during arthritis induction. To clarify this discrepancy,
      the CAIA response was independently analyzed in our CD69-deficient mice. In these
      experiments, the inflammatory response was unaffected by CD69 deficiency.
      Additionally, the in vivo down-regulation of CD69 expression by treatment of wild
      type mice with the anti-CD69 mAb 2.2, which mimics the CD69-deficient phenotype,
      did not affect the course of arthritis in this model. Moreover, down-regulation
      of CD69 expression increased expression in arthritic joints of key inflammatory
      mediators, including IL-1beta, IL-6 and the chemokine MCP-1. Neutrophil
      accumulation in zymosan-treated air pouches and in thioglycolate-treated
      peritoneal cavities was also unaffected in CD69-deficient mice. In addition, CD69
      expression was absent in activated neutrophils. Taken together, these results
      rule out a significant stimulatory role for CD69 in acute inflammatory responses
      mediated by neutrophils.

PMID- 16983730
TI  - On the unpredictability of odor.
AB  - The relationship between molecular structure and odor has fascinated and puzzled
      chemists for more than a century. Despite a great deal of research on structure
      odor relationships, prediction of the odor of a novel molecule remains a
      statistical exercise and models only provide a probability of the character,
      threshold, and intensity. Surprises are still commonplace, and serendipity
      continues to be an important factor in the discovery of novel fragrant molecules.
      Recent advances in our understanding of the mechanism of olfaction provide an
      explanation for this and suggest that our ability to predict odor properties of
      molecules will not improve significantly in the near future.

PMID- 16983733
TI  - Randomized clinical trial to determine the effect of nasogastric drainage on
      tracheal acid aspiration following oesophagectomy (Br J Surg 2006; 93: 547 -552).

PMID- 16983735
TI  - Collision-induced fragmentation pathways including odd-electron ion formation
      from desorption electrospray ionisation generated protonated and deprotonated
      drugs derived from tandem accurate mass spectrometry.
AB  - The rapid desorption electrospray ionisation (DESI) of some small molecules and
      their fragmentation using a triple-quadrupole and a hybrid quadrupole time-of
      flight mass spectrometer (Q-ToF) have been investigated. Various scanning modes
      have been employed using the triple-quadrupole instrument to elucidate
      fragmentation pathways for the product ions observed in the collision-induced
      dissociation (CID) spectra. Together with accurate mass tandem mass spectrometry
      (MS/MS) measurements performed on the hybrid Q-ToF mass spectrometer, unequivocal
      product ion identification and fragmentation pathways were determined for
      deprotonated metoclopramide and protonated aspirin, caffeine and nicotine. Ion
      structures and fragmentation pathway mechanisms have been proposed and compared
      with previously published data. The necessity for elevated resolution for the
      differentiation of isobaric ions are discussed.

PMID- 16983736
TI  - Routine surgical pathology in general surgery (Br J Surg 2006 93 362-368).

PMID- 16983739
TI  - Imaging technology of the future.

PMID- 16983740
TI  - Current role of radiofrequency ablation for the treatment of colorectal liver
      metastases.
AB  - BACKGROUND AND METHOD: This paper reviews the current status of radiofrequency
      ablation in the treatment of colorectal liver metastases. Relevant studies with
      at least ten patients that reported rates of complete tumour ablation, local
      recurrence, or survival from 1 to 5 years after treatment were included in the
      review. RESULTS AND CONCLUSION: Only six studies that reported at least 3-year
      survival were identified, with results ranging from 37 to 58 per cent. Some of
      these figures are promising, given that the patients were considered to have
      unresectable disease. However, available evidence is limited and hepatic
      resection remains the standard of care when feasible; radiofrequency ablation
      cannot be considered an equivalent. Radiofrequency ablation does, however, appear
      to have a role in treating unresectable disease, and may also be used in
      conjunction with resection to extend its limits.

PMID- 16983741
TI  - Long-term results of a randomized trial comparing preoperative short-course
      radiotherapy with preoperative conventionally fractionated chemoradiation for
      rectal cancer.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy does not alter anal sphincter
      preservation or postoperative complications compared with short-course
      radiotherapy alone in patients with clinical stage T3 or T4 resectable rectal
      cancer. The aim of this study was to compare survival, local control and late
      toxicity in the two treatment groups. METHODS: The study randomized 312 patients
      to receive either preoperative irradiation (25 Gy in five fractions of 5 Gy) and
      surgery within 7 days or chemoradiation (50.4 Gy in 28 fractions of 1.8 Gy, bolus
      5-fluorouracil and leucovorin) and surgery 4-6 weeks later. The median follow-up
      of living patients was 48 (range 31-69) months. RESULTS: Early radiation toxicity
      was higher in the chemoradiation group (18.2 versus 3.2 per cent; P < 0.001). The
      actuarial 4-year overall survival was 67.2 per cent in the short-course group and
      66.2 per cent in the chemoradiation group (P = 0.960). Disease-free survival was
      58.4 versus 55.6 per cent (P = 0.820), crude incidence of local recurrence was
      9.0 versus 14.2 per cent (P = 0.170) and severe late toxicity was 10.1 versus 7.1
      per cent (P = 0.360) respectively. CONCLUSION: Neoadjuvant chemoradiation did not
      increase survival, local control or late toxicity compared with short-course
      radiotherapy alone.

PMID- 16983742
TI  - Letter 1: Systematic review of outcome of synchronous portal-superior mesenteric
      vein resection during pancreatectomy for cancer (Br J Surg 2006; 93: 662-673).

PMID- 16983743
TI  - Letter 2: Systematic review of outcome of synchronous portal-superior mesenteric
      vein resection during pancreatectomy for cancer (Br J Surg 2006; 93: 662 -673).

PMID- 16983745
TI  - Free peritoneal tumour cells are an independent prognostic factor in curatively
      resected stage IB gastric carcinoma (Br J Surg 2006; 93: 325 -331).

PMID- 16983748
TI  - Ageing: connected clues?

PMID- 16983747
TI  - Neurodegeneration and neuroprotection in multiple sclerosis and other
      neurodegenerative diseases.
AB  - Multiple sclerosis is considered a disease of myelin destruction; Parkinson's
      disease (PD), one of dopaminergic neuron depletion; ALS, a disease of motor
      neuron death; and Alzheimer's, a disease of plaques and tangles. Although these
      disorders differ in important ways, they also have common pathogenic features,
      including inflammation, genetic mutations, inappropriate protein aggregates
      (e.g., Lewy bodies, amyloid plaques), and biochemical defects leading to
      apoptosis, such as oxidative stress and mitochondrial dysfunction. In most
      disorders, it remains uncertain whether inflammation and protein aggregation are
      neurotoxic or neuroprotective. Elucidating the mechanisms that orchestrate
      neuronal diseases should facilitate development of neuroprotective and
      neurorestorative strategies.

PMID- 16983753
TI  - Molecular mechanisms of spermatogonial fate control: lesson from gene knockouts.

PMID- 16983756
TI  - Whitespot.

PMID- 16983755
TI  - Item 291.

PMID- 16983757
TI  - Bibliography. Current world literature. Forensic psychiatry.

PMID- 16983758
TI  - 13 candidates compete to be next WHO Director-General.

PMID- 16983759
TI  - Hospitals may see stars. HHS' Leavitt floats trial balloon on ratings.

PMID- 16983760
TI  - CMS price data irrelevant: ASCs.

PMID- 16983761
TI  - [Practical use of self-measured blood pressure at home].

PMID- 16983762
TI  - [Seasonal variation in blood pressure].

PMID- 16983763
TI  - [Japan Arteriosclerosis Longitudinal Study].

PMID- 16983764
TI  - [BNP as a biomarker of hypertensive complications].

PMID- 16983765
TI  - [Clinical significance of high-sensitivity C-reactive protein].

PMID- 16983766
TI  - [Intima media thickness (IMT) of carotid artery].

PMID- 16983767
TI  - [Should drug treatment be started with monotherapy or combination therapy for
      patients with hypertension].

PMID- 16983768
TI  - [The lower, the better: is that true in drug therapy for patients with
      hypertension?].

PMID- 16983769
TI  - [Beta-blockers for patients with hypertension].

PMID- 16983770
TI  - [Novel actions of calcium channel blockers].

PMID- 16983771
TI  - [Antihypertensive treatment in the elderly].

PMID- 16983772
TI  - [Preeclampsia: recent advances].

PMID- 16983773
TI  - [Hypertension in children and adolescents].

PMID- 16983774
TI  - [Mild hypertension].

PMID- 16983775
TI  - [Overview on management of hypertension for prevention of and therapy for
      stroke].

PMID- 16983776
TI  - [PROGRESS].

PMID- 16983777
TI  - [HOMED-BP].

PMID- 16983778
TI  - [HOSP study].

PMID- 16983779
TI  - [HOPE study].

PMID- 16983780
TI  - [Lifestyle modification for patients with hypertension].

PMID- 16983781
TI  - [Goal blood pressure].

PMID- 16983782
TI  - [Controversial matters in the guidelines for the therapy of patients with
      hypertension].

PMID- 16983783
TI  - [Changes in practice guidelines for hypertension therapy].

PMID- 16983784
TI  - The future of geriatrics--a new horizon or a false dawn?

PMID- 16983785
TI  - Diabetes and cognitive function in older adults.

PMID- 16983786
TI  - Abstracts of the 16th European Meeting of Hypertension, Madrid, Spain, June 12
      15, 2006.

PMID- 16983787
TI  - Abstracts of the AAOMS 88th Annual Meeting, October 3-7, 2006, San Diego,
      California, USA.

PMID- 16983789
TI  - [Abstracts of the 11th International Internal Medicine Congress of the Hospital
      de Clinicas].

PMID- 16983790
TI  - [The 48th Congress of the Japanese Society of Clinical Hematology.  Fukuoka,
      Japan. October 6-8, 2006. Program and Abstracts].

PMID- 16983788
TI  - Suicide, assisted suicide and euthanasia: international perspectives.
AB  - Suicide, assisted suicide and euthanasia are elusive and controversial issues
      worldwide. To discuss such issues from only one perspective may be limiting.
      Therefore, this paper was written by authors from various regions, each of whom
      has been asked to reflect on the issues. The countries/cultures are: Australia,
      China, Cuba, Ireland, India, Japan, Russia, South Africa, The Netherlands, North
      America (Turtle Island) and United States. Historically and today, suicide is
      viewed differently. Assisted suicide and euthanasia are equally seen from
      multifarious perspectives. Highlighting development in the Netherlands,
      Australia's Northern Territory and Japan (ie. the famous Yamanouchi Case), the
      review shows growing re-examination of the right to die. There appear, however,
      to be no uniform legal and ethical positions. Further debate and discussion
      globally is needed to avoid myopic perspectives.

PMID- 16983791
TI  - [The 34th annual meeting of the Japanese Society of Clinical Immunology. Tokyo,
      Japan. October 2-3, 2006. Abstracts].

PMID- 16983792
TI  - Abstracts of the 8th Congress of the Polish Society of Clinical Neurophysiology,
      Kielce, 22-24 June 2006.

PMID- 16983794
TI  - Abstracts of the XXII Brazilian Congress of Neurology, 19-23 August 2006, Recife,
      Brazil.

PMID- 16983795
TI  - Abstracts of the 95th Annual Meeting of the Poultry Science Association, July 16
      19, 2006, Edmonton, Canada.

PMID- 16983796
TI  - 2006 Michigan State Medical Society membership directory.

PMID- 16983793
TI  - Open pancreaticogastrostomy after pancreaticoduodenectomy: a pilot study.
AB  - Management of the pancreatic stump following pancreaticoduodenectomy (PD) has
      always been a main source of concern among pancreatic surgeons. The present pilot
      study describes the reconstructive technique of anterior transgastric
      pancreaticogastrostomy (PG) after pylorus-preserving PD. Outcome in 50 patients
      with "soft" residual parenchyma treated with this technique is also reported. The
      average duration of the intervention was 351 minutes (range, 240-360); only two
      patients needed intraoperative transfusion with 2 units of blood. The
      postoperative period involved complications in 15 cases (30%). In particular,
      four patients developed pancreatic fistulas (8%), which were grade C in three
      cases (6%) and grade B in one patient (2%). Two patients (4%) presented with
      enteric fistula from erosion from a drain. Two patients experienced
      perianastomotic fluid collections associated with delayed gastric emptying (4%)
      and a clinically silent 5-cm abdominal collection was observed in an additional
      case. Bleeding of a gastric ulcer was treated in one case and four patients
      developed bronchopneumonia. None of the complications required a second surgical
      intervention and there were no deaths. One patient with a symptomatic fluid
      collection was treated by ultrasound-guided cutaneous drainage. The mean
      hospitalization time was 11.1 days (range, 8-25 days). The results obtained in
      this pilot study appear encouraging and merit further analysis in a randomized
      comparative trial.

PMID- 16983797
TI  - Common reasons for hospitalization among adult patients with diabetes.
AB  - OBJECTIVE: To determine reasons for hospitalization among adult patients with
      diabetes. METHODS: A cross-sectional analysis was conducted of hospital
      discharges in the state of Georgia for the years 1998 through 2001 that contained
      either a primary or a coexisting diagnosis of diabetes. With use of the Clinical
      Classification Software of the Agency for Healthcare Research and Quality, the
      principal diagnoses among diabetes-related hospital discharges were organized
      into diagnostic categories. RESULTS: Diabetes was listed as a diagnosis in 14% of
      all Georgia hospital discharges of adult patients during our study period (57%
      women; 62% non-Hispanic white; mean age, 64 years; mean length of stay, 5.7 days;
      and mean hospital charge, 13,540 dollars). Among patients with a diagnosis of
      diabetes, the 3 most common categories of discharges were "diseases of the
      circulatory system" (33%), "endocrine, nutritional, and metabolic; immunity
      disorders" (13%), and "diseases of the respiratory system: (11%). When infections
      were identified and aggregated, however, these conditions became the second most
      frequent discharge category (14% of all hospital discharges among patients with
      diabetes). "Congestive heart failure," "coronary atherosclerosis," and "acute
      myocardial infarction" were the first, second, and fifth most frequently found
      unique diagnoses, respectively, among patients with diabetes. CONCLUSION: In this
      study, diseases of the circulatory system were the most common diagnoses in
      hospital discharge data for adult patients with diabetes in Georgia. Hospitals
      should be cognizant of the increased burden placed on them by diabetes, and
      outpatient treatment of diabetes should focus on prevention of cardiovascular
      diseases to avoid hospitalizations.

PMID- 16983799
TI  - Further thoughts on hyperosmolar hyperglycemic crisis.

PMID- 16983798
TI  - American College of Endocrinology and American Diabetes Association consensus
      statement on inpatient diabetes and glycemic control.

PMID- 16983800
TI  - Promoting equality and diversity in UK biomedical and clinical research.

PMID- 16983801
TI  - JmjC-domain-containing proteins   and histone demethylation.
AB  - Histone methylation has important roles in regulating gene expression and forms
      part of the epigenetic memory system that regulates cell fate and identity.
      Enzymes that directly remove methyl marks from histones have recently been
      identified, revealing a new level of plasticity within this epigenetic
      modification system. Here we analyse the evolutionary relationship between
      Jumonji C (JmjC)-domain-containing proteins and discuss their cellular functions
      in relation to their potential enzymatic activities.

PMID- 16983802
TI  - Sharing saves lives.

PMID- 16983803
TI  - Animal, vegetable or mineral?

PMID- 16983805
TI  - [Air kerma standards for X- and gamma rays and future plans for dosimetric
      standards at AIST].

PMID- 16983804
TI  - Livable communities for adults with disabilities.
AB  - In 2004, the National Council on Disability (NCD) commissioned the Center for
      Home Care Policy and Research to research and prepare a report on the topic of
      "livable communities" for adults with disabilities. The following is a summary of
      the major findings in the report and the priority action steps that communities
      should take to become more livable for people with disabilities. The report was
      published by the National Council on Disability in December 2004. The National
      Council on Disability is an independent federal agency making recommendations to
      the President and Congress to enhance the quality of life for all Americans with
      disabilities and their families. The full report, entitled Livable Communities
      for Adults with Disabilities, includes numerous examples of communities that have
      made improvements in their livability for people with disabilities. It is
      available on the Council's website, www.ncd.gov.

PMID- 16983806
TI  - [Evaluation of absorbed dose based on "standard dosimetry 01" for high-energy X
      ray beam therapy].

PMID- 16983807
TI  - [Estimation of absorbed dose determination in high energy electron beams for
      radiotherapy].

PMID- 16983808
TI  - [Evaluation of dosimetric parameters for high-energy photon and electron beams].

PMID- 16983810
TI  - [Implications of Gy and Sv used in medical fields].

PMID- 16983809
TI  - [Voxel-based specific regional analysis system as an adjunct to diagnosis of
      early Alzheimer's disease].

PMID- 16983811
TI  - [CT imaging diagnosis of vessel diseases].

PMID- 16983812
TI  - [MRA of lower limbs from the abdomen].

PMID- 16983814
TI  - [Introduction of remote service security guideline].

PMID- 16983813
TI  - [Present status of low energy X-ray standard at AIST and related problems].

PMID- 16983815
TI  - [Penetrating the genome].

PMID- 16983816
TI  - [Prognosis value of the pp65 antigenemia and semi-quantitative PCR in the
      detection of the CMV reactivation in bone marrow grafted patients].
AB  - In this article a Cytomegalovirus (CMV) antigenemia and semiquantitative PCR
      retrospective evaluation of 26 bone marrow allo-grafted patients for different
      haematological disease is reported. Eighteen patients had a CMV reactivation
      despite a prophylactic treatment, seven of those patients had both positive
      antigenemia pp65 and positive semi-quantitative CMV PCR. During CMV reactivation,
      3 patients developed a CMV disease despite a pre-emptive therapy. The follow up
      of the antigenemia was performed since D21 until D100 post transplantation, the
      antigenemia positivity occurred at D53 and was preceded about 7 days by CMV PCR
      positivity The CMV disease wasn't associated with a high viral load. All patients
      that had CMV reactivation had a positive CMV serology before the graft, whereas
      only 37.5% of the patients who did not reactivate had a positive CMV serology.
      Respectively half patients who reactivated and only 12.5% of those who didn't had
      a Graft versus host disease (GVHD), witch preceded the reactivation about 21 days
      in six of the formers. Clinical and biological signs presented by our patients in
      this cases report, seems to be associated more with the GVHD than with CMV
      reactivation.

PMID- 16983817
TI  - [In vivo sensitivity of Plasmodium faciparum to chloroquine and sulfadoxine
      pyrimethamine in the Bobo Dioulasso region (1998-2001): risk factors associated
      with treatments failures to the two drugs].
AB  - The therapeutic efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP)
      was determined over a 4 year period (1998-2001) in Bobo Dioulasso, Burkina Faso,
      with an analysis of the risk factors associated to treatment failures to the 2
      drugs. In total, 2008 children (6 months-15 years old) attending in 4 health
      centres (1 urban and 3 rural) were included in the study. Children were
      alternatively allocated to either CQ or SP The WHO 14-days in vivo field test was
      carried out. PCV was measured at day 0 and 14. CQ treatment failure was 24.4%
      (229/940), most of them being late failures. Between 1998 and 2001 a significant
      increase in CQ treatment failure (p < 0.001) was observed. SP showed a good
      efficacy with a total treatment failure of 4.4% (33/749). However; a significant
      increase of resistance to this drug (p=0.001) was also observed between 1998 and
      2001. Among children with anaemia at day 0.85% (23/27) were no more anaemic by
      day 14 in the SP group, while in the CQ group the proportion was lower; 69%
      (27/39). However the difference between the two drugs was not significant (p >
      0.1). Univariate analysis showed that the site, the age of children, the time of
      recruitment and the parasitaemia were significantly associated with CQ treatment
      failure. In the multivariate analysis these 4 variables remain significantly and
      independently associated with the risk of CQ treatment failure. After adjusting
      for the effect of the 3 other factors, the risk of treatment failure was reduced
      by half in rural area compared to urban area as well as in children of 5-15 years
      of age compared to those under 5. The risk of treatment failure was significantly
      increased in 2000-2001 (OR = 1.66, p < 0.05) as compared to the 2 previous years
      (1998-1999). It was also twice higher in children with parasitaemia > or =
      16,000/microl than in those having a lower parasitaemia. For SP we have not
      observed such connexions with the univariate and multivariate analysis.

PMID- 16983818
TI  - [Genetic diversity of P. falciparum and pathogenesis of the severe malarial
      anaemia in children under 5 years old in the province of Boulgou, Burkina Faso].
AB  - The clinical presentation of malaria mainly the severe form may be related to
      Plasmodium falciparum msp-2 (merozoite surface protein 2) specific family To
      verify this hypothesis, during the high malaria transmission season in 2001; we
      analyzed the allelic polymorphism of the msp-2 gene of P. falciparum in children
      under 5 years old with different presentation of malaria in the regional Hospital
      and at community level in the Boulgou Province (Burkina Faso). A total of 405
      children (107 severe malarial anaemia cases, 102 severe malaria cases without
      severe anaemia and 196 non severe malaria cases) were enrolled in the study. The
      frequencies of the FC27 were 89.2% in severe malarial anaemia children group,
      then 89.7% and 86.9% respectively in severe malaria non anaemic children cases
      and non severe malaria cases (P = 0.4). The frequencies of the 3D7 were 72.5%;
      84.1% and 77% respectively severe malaria non anaemic children, severe malarial
      anaemia cases and non severe malaria cases (P = 0.7). The complexity of the FC27
      genotypes was significantly higher in children with severe malaria (with and
      without severe anaemia) compared to the non severe malarial children (P <<
      0.001). No significant difference was pointed up in the complexity of the 3D7
      genotypes.

PMID- 16983819
TI  - [Trypanosomatid (Protozoa, Kinetoplastida) parasites of sloths (Mannmalia,
      Xenarthra)].
AB  - Worldwide famous for their slothfulness, sloths are xenarthran mammals living in
      the tropical forests of the New World. In these highly biodiverse habitats,
      sloths are implicated in long-term interactions with many organisms. They are
      especially involved in the parasitic cycles of various trypanosomatids including
      human parasites. This review describes the different species of the genera
      Leishmania, Endotrypanum and Trypanosoma that infect sloths. The improvement of
      the preventive method efficacy against synanthropozoonotic diseases due to
      several of these protozoa relies on studies on the ecology and biology of wild
      reservoir hosts such as sloths.

PMID- 16983820
TI  - [Acute peritoneal tuberculosis in HIV-infected patients. Study of 4 cases in
      Abidjan, Cote-d'Ivoire].
AB  - This paper presents 4 cases of histologically verified peritoneal tuberculosis in
      HIV-infected patients followed in a 18 month-period. The patients were admitted
      in emergency and were suspected of present acute appendiceal peritonitis. There
      were 3 females of 18, 22 and 27 years old, and a 41-year-old male. The main
      symptoms were acute abdominal pain (4 cases), fever superior to 38 degrees C (4
      cases) and abdominal defence (4 cases). Laboratory findings were
      hyperleucocytosis with lymphocytic predominance, anemia and CD4+ rate variable
      from 250 to 460/mm3. They underwent emergency laparotomy which led to diagnosis
      of peritoneal tuberculosis by histopathological analysis of peritoneal biopsies.
      Two patients died from surgery at days 3rd and 10th. The 2 remaining patients
      were successfully treated by tuberculostatic tritherapy with rifampicin,
      isoniazid, and pirazinamid. Acute peritoneal tuberculosis in HIV-infected
      patients is not to be missed in our practice. It must be considered in
      differential diagnosis of acute abdomens.

PMID- 16983821
TI  - [Lupus tuberculosis: a cause of medio-facial mutilation not to be ignored].
AB  - Medio-facial mutilations are a real problem from a diagnosis and prognosis point
      of view. Various etiologies may be in question, namely bacterial, parasitic,
      mycotic, viral infections or yet predisposing factors such as denutrition or a
      immunodepression. Among these etiologies, the lupus tuberculosis remains a major
      concern to be taken into account in poor socio-economic background. We report two
      cases of lupus tuberculosis in teen-agers whose diagnosis difficulty induced
      sequellae although limited by a further appropriate care management. The clinical
      spectrum of the cutaneous tuberculosis and the place of this affection featuring
      ahead of other medio-facial mutilations etiologies remain important in tropical
      area.

PMID- 16983822
TI  - [Epidemiological aspects of human and animal rabies in the urban area of Bamako,
      Mali].
AB  - The district of Bamako is the political and economical capital city of Mali with
      1,800,000 inhabitants. The goal of the present retrospective study was to
      determine the frequency of animal bites, human and animal rabies on the one hand
      and to determine the frequency and the nature of mad animals on the other hand
      from January 2000 to December 2003 (4 years). To achieve this goal, we have
      analysed registers and documents related to rabies in the department of
      prevention and fight against diseases, the central veterinary laboratory, and
      also at the lazaret clinic involved in caring for human rabies cases. Human
      rabies diagnosis has been brought up based upon the following clinical arguments:
      agitation and lethal hydrophobia within few days following bites by known or
      unknown animal. Agitation and aggressiveness followed by the animals' death
      within an observation period of 15 days maximum, allowed to evoke the diagnosis
      in animals. In Bamako an average of 1470 persons have been bitten each year. In
      97.1% of the cases, the mad animal was a dog; cats (1.6%), donkeys, horses,
      cattle and rats (1.4%) have also been identified on a total of 5870 cases of
      notified human bites by animals; 10 cases of notified human rabies have been
      recorded. The dog has been incriminated in 6 cases of human rabies out of 10, in
      the 4 other cases, it has not been possible to identify the mad animal. Among the
      3924 mad animals in observation at the veterinary clinic, 187 have been
      clinically mad that is 4.8%. The rabies virus has also been researched by direct
      immunofluorescence in 121 specimens of dead mad animals brain. This research has
      been positive in 119 cases among which 116 dogs, 2 sheep and 1 cow. Anyway the
      vaccinal status of people bitten by mad animals has not been clearly established.
      According to these results, we recommend the implementation of a national
      specific program to eradicate rabies in Bamako.

PMID- 16983823
TI  - [Malaria morbidity in Barkedji, village of Ferlo, in Senegal Sahelian area].
AB  - A study of malaria morbidity was carried out from November 1994 to October 1995,
      in a Ferlo village (Barkedji) characterized by a long persistence of the
      temporary ponds. The objective was to evaluate the repercussions of the strong
      and long anopheles transmission in humans. A clinical follow-up of a group of
      residents was conducted at home every 10 days by an investigator trained for
      taking axillary temperature and making thick smears, when suspecting malaria.
      Were included in the group, 123 voluntary subjects among whom 50% were children
      under 10 years old. Any feverish subject (T degree >37 degrees 5) or subject
      presenting other malaria symptoms (headaches, hot body shivers, sweats, aches...)
      was regarded as having a malaria attack as well as a parasitemia >2500 P/mm3 in
      children aged of 0 to 14 years old and 1000 P/mm3 in the oldest. During the study
      subjects with at least one feverish access, plasmodium infection and malaria
      attack were 58%, 33% and 22%, respectively. On 172 hyperthermias observed, 49%
      were accompanied by a circulating parasitemia and 30% corresponded to malaria
      attack. The feverish subjects (74% vs. 42%), the subjects with parasitemia (51%
      vs. 16%) and the cases of malaria (34% vs. 10%) were more frequently encountered
      in children under10 than in the oldest. The cases of malaria attacks were more
      frequent from November to January (70%). The strong intensity of malaria
      transmission in Barkedji and the persistence of its temporary ponds until January
      were sufficient to influence the level of malaria morbidity and consequently the
      development of an anti-malaria immunity by the indigenous population.

PMID- 16983824
TI  - [The re-emergence of the human African trypanosomiasis in Kerou, Benin].
AB  - Located in the northern part of Benin, the district of Kerou is an historical HTA
      focus of the 60s formerly called the "Atacora focus". This survey was conducted
      in 2001 to determine the prevalence of HAT in Kerou. The methodology consisted in
      a cross-sectional survey based on random sampling with two levels of
      stratification. 3367 persons were included (i=5%). After a screening based on
      CATT test with total blood test, the examination of trypanosomae was performed
      with QBC on the subjects that have some persistent antibodies above serum
      dilution at 1/4, followed by lumbar puncture. For 3367 surveyed subjects, the
      CATT seroprevalence test with total blood sample is 4.2% and it is 2.4% with
      serum dilution at 1/8. The research of trypanosomae with QBC is positive in 48
      patients and the prevalence is 1.4%. The community survey conducted among 106
      positive persons with CATT test serum at 1/4 dilution has revealed that 71 (67%)
      persons have never left the area since their birth. The HAT is actually emerging
      in Atacora district in the north of Benin, especially in Kerou.

PMID- 16983825
TI  - [Management of malaria in Togolese communities].
AB  - The objective of this study was to collect community basis data on prevention and
      home management of malaria for the future assessment of "Roll Back Malaria", the
      new world strategy of fighting against malaria. The study was carried out in 3
      districts in Togo. Mothers were questioned about the quality of home management
      of uncomplicated malaria on 951 children aged under 5. Fathers were questioned
      about the use of mosquito bed nets in 597 households, and 246 women were
      interviewed about the prevention of malaria during pregnancy. Home management of
      children under treatment was correct in only 38.1% of cases and the drug
      observance was followed by only 35.4% of patients. Mosquito nets were used in
      30.5% of households and only 16.5% were treated with insecticides. Only 22.7% of
      children under 5 slept under mosquito nets. 80% women made at least one antenatal
      visit and 74.4% received regular malaria chemoprophylaxis. Many efforts should be
      made in Togo to increase the quality of home management of malaria and the use of
      insecticide-treated bed nets.

PMID- 16983826
TI  - [Diagnosis of malaria in Antananarivo City: examination of the results obtained
      at the Institut Pasteur de Madagascar from 2001 to 2004].
AB  - Malaria diagnosis is part of the daily activities of the Clinical Biology Center
      (CBC) of the Institut Pasteur de Madagascar in Antananarivo. Over a period of
      four years (2001-2004), regardless the methods being used, out of 6537 blood
      samples examined, 159 (2.43%) tests were positive. All four species of Plasmodium
      infecting human. were detected with a high prevalence of P. falciparum (87.2%).
      49/159 patients were foreigners, but their files did not allow us to distinguish
      imported from locally acquired malaria cases. Also, among Malagasy patients,
      there was no possibility to recognize introduced malaria cases (contracted in
      coastal areas). In Madagascar malaria remains a public health problem. But fever
      and recent history of fever are often considered and treated as malaria. Our
      results demonstrated that confirmed malaria rate was very low. Reporting malaria
      on the basis of clinical signs overestimates malaria cases at the national level.
      The importance of malaria biological diagnosis is discussed in this article.

PMID- 16983827
TI  - [Malaria prevalence at delivery in four maternity hospitals of Kinshasa City,
      Democratic Republic of Congo].
AB  - In areas with stable transmission, malaria is an alarming threat both for mothers
      (anemia) and fetus (abortion, premature birth, a birth ponderal deficit, death in
      utero). Our study aims at estimating the malaria prevalence among parturients and
      their newborn babies in Kinshasa, Democratic Republic of Congo, in order to
      conduct the national programme of control. Between September and November 2004,
      196 pregnant women aged of 14 to 45 years old (average: 25.8 years) were
      recruited consecutively from four maternity hospitals in Kinshasa; those who
      received antimalarial drugs 2 weeks before delivery were not selected. The socio
      demographic information and clinical symptoms/signs were obtained by
      questionnaire. Blood smears were performed on the mother's capillary blood, by
      placental apposition and with the newborn baby's blood. Smears were stained with
      Giemsa. 42 out of the 196 parturients (21%) were infected by Plasmodium
      falciparum. Parasites were found both in capillary blood and placenta of the 37
      parturients; in 5 cases, only the placental appositions were positive. Prevalence
      was higher among primiparae (26.5%) than among multiparae (18.8%) (p = 0.20).
      19.7% of the parturients who received an Intermittent Preventive Treatment (IPT)
      with sulfadoxine-pyrimethamin (SP) were positive. 13 out of the 196 newborn
      babies had a positive malaria smear. Malaria at delivery is thus a reality in
      Kinshasa, despite the use of SP as an IPT. The weak protection conferred on the
      IPT could be explained by the inefficacy of the SP a failing in prenatal record
      andlor by the low compliance of the mothers with this strategy This is the reason
      why we strongly recommend a large-scale evaluation of this strategy.

PMID- 16983828
TI  - [Direct sputa examination limits in tuberculosis active detection in 200
      immigrant candidates in United States of America].
AB  - The Cote-d'Ivoire Pasteur Institute unit of Tuberculous and Nontuberculous
      Mycobacteria carried out 600 smears stained by Ziehl-Neelsen in 200 immigrant
      candidates for the U.S.A. The sputa of 44 of them were put in culture on
      Lowenstein-Jensen medium. Eight (4%) candidates had active pulmonary tuberculosis
      among whom 5 had smear negative sputum. The pulmonary tuberculosis active
      detection performed on target population with accessible and sensitive tool can
      contribute to strengthen the fight against tuberculosis in endemic areas.

PMID- 16983829
TI  - [Comparison of specific composition and mosquitoes population dynamics in two
      villages of the centre of Cote-d'Ivoire, with and without irrigated rice growing
      area].
AB  - Entomological surveys were undertaken between October 1994 and August 1995 and
      from April to August 1995 in the villages of Kafine and Pekaha, respectively
      These villages are located in the centre of Cote-d'Ivoire in a humid savannah
      area in the prefecture of Niakaramandougou. Rice plots are located to about 500
      meters from the first habitations of Kafine. They also form an enclosure around
      the village causing a great culicidian nuisance. On the other hand in the village
      of Pekaha, situated at 8 km from the enclosure, one can find a non-developed low
      ground area with swamps according to the season which has caused the
      multiplication of anthropophilic Culicidae. Five genera of mosquito were caught
      in the two villages: Anopheles, Aedes, Culex, Mansonia and Uranotaenia. The genus
      Anopheles is by far the most predominant in Kafine with 84.3% (n=17556).
      Mansonia, Culex and Aedes respectively constitute 12%, 3% and 0.01% of the total
      anthropophilic mosquitoes. In the contrary the genus Mansonia was the most
      predominant in Pekaha with 78.2% (n=6642). Anopheles, Aedes and Culex
      respectively represent 13.2%, 8.3% and 0.1% of the total number of mosquitoes
      caught during the surveys. If in the village of Kafine, the culicidian nuisance
      is mainly due to anopheles mosquitoes (84.3%) and particularly to An. gambiae
      s.s. (70.6%), in the village of Pekaha, dwellers suffer more from Mansonia
      (78.2%) bites than those of Anopheles (13.2%).

PMID- 16983831
TI  - Computer evaluation of network dynamics models with application to cell cycle
      control in budding yeast.
AB  - Cellular processes are governed by complex networks of interacting genes and
      proteins. Theoretical molecular biologists attempt to describe these processes
      via mathematical models by writing biochemical reaction equations. Modellers are
      building increasingly larger and complex mathematical models to describe these
      cellular processes, making model evaluation a time consuming and difficult task.
      The authors describe an automatable process for model evaluation and a software
      system that implements this process. The software is adaptable to many types of
      models and is freely available along with all needed data files. The cell cycle
      control system for budding yeast is known in fine detail and constrained by more
      than 100 phenotypic observations in mutant strains. As an example, the authors
      apply their process to a model of cell cycle control in budding yeast containing
      dozens of regulatory equations and explaining nearly all of the known mutant
      phenotypes.

PMID- 16983830
TI  - Template-driven gene selection procedure.
AB  - The hierarchical clustering and statistical techniques usually used to analyse
      microarray data do not inherently represent the underlying biology. Herein, a
      hybrid approach involving characteristics of both supervised and unsupervised
      learning is presented. This approach is based on template matching in which the
      interaction of the variables of inherent malignancy and the ability to express
      the malignant phenotype are modelled. Immortalised normal urothelial cells and
      bladder cancer cells of different malignancy were grown in conventional two
      dimensional tissue culture and in three dimensions on extracellular matrices
      (ECMs) that were either permissive or restrictive for expression of the malignant
      phenotype. The transcriptome represents the effects of two variables--inherent
      malignancy and the modulatory effect of ECM. By assigning values to each of the
      biological variables of inherent malignancy and the ability to express the
      malignant phenotype, a template was constructed, which encapsulated the
      interaction between them. Gene expression correlating both positively and
      negatively with the template was observed, but when iterative correlations were
      carried out, the different models for the template converged on the same actual
      template. A subset of 21 genes was identified, which correlated with two a priori
      models or an optimised model above the 95% confidence limits identified in a
      bootstrap resampling with 5000 permutations of the data set. The correlation
      coefficients of expression of several genes were > 0.8. Analysis of upstream
      transcriptional regulatory elements (TREs) confirmed that these genes were not a
      randomly selected set of genes. Several TREs were identified as significantly
      over-expressed in the sample of 20 genes for which TREs were identified, and the
      high correlations of several genes were consistent with transcriptional co
      regulation. The authors suggest that the template method can be used to identify
      a unique set of genes for further investigation.

PMID- 16983832
TI  - Computational modelling of ErbB family phosphorylation dynamics in response to
      transforming growth factor alpha and heregulin indicates spatial compartmentation
      of phosphatase activity.
AB  - Members of the ErbB receptor family are associated with several cancers and
      appear to be providing useful targets for pharmacological therapeutics for
      tumours of the lung and breast. Further improvements of these therapies may be
      guided by a quantitative, dynamic integrative systems understanding of the
      complexities of ErbB dimerisation, trafficking and activation, for it is these
      complexities that render difficult intuiting how perturbations such as drug
      intervention will affect ErbB signalling activities. Towards this goal, we have
      developed a computational model implementing commonly accepted principles
      governing ErbB receptor interaction, trafficking, phosphorylation and
      dephosphorylation. Using this model, we are able to investigate several
      hypotheses regarding the compartmental localisation of dephosphorylation. Model
      results applied to experimental data on ErbB 1, ErbB2 and ErbB3 phosphorylation
      in H292 human lung carcinoma cells support a hypothesis that key
      dephosphorylation activity for these receptors occurs largely in an
      intracellular, endosomal compartment rather than at the cell surface plasma
      membrane. Thus, the endocytic trafficking-related compartmentalisation of
      dephosphorylation may define a critical aspect of the ErbB signalling response to
      ligand.

PMID- 16983833
TI  - Cell surface dynamics: the balance between diffusion, aggregation and
      endocytosis.
AB  - The cell membrane lies at the interface between an extracellular set of signals
      and the appropriate intracellular response. Specifically, lymphocyte activity is
      determined by the spatial and structural response to antigens, as mediated by
      cell surface receptors. In order to correlate experimentally observed cellular
      activities, such as secretion, anergy, death, survival and division to external
      stimuli, it is necessary to monitor cell surface dynamics. B-lymphocyte
      activation results from the stimulation by large immune complexes comprising
      antigens, B-cell receptors (BcRs) and co-receptors. Compartmentalisation of the
      interacting molecular components is required in order to assure the rapid
      initiation of specialised and sustained signalling cascades. In this study, a
      Monte Carlo simulation of the cell membrane dynamics was developed to clarify the
      receptor dynamics, aggregation mechanisms and their combined effect on cellular
      functions. This simulation is based on experimentally measured parameters and
      represents a feasible, advanced and reliable framework to investigate the cell
      surface. The current study focussed on B-cell surface dynamics. A model
      demonstrating the basic properties of BcR dynamics and how BcR kinetics is
      affected by lipid rafts is developed. The authors studied BcR interactions with
      multivalent ligands and the influence of lipid rafts on this interaction.
      Finally, the dynamics of the initial steps of BcR-mediated cell activation is
      estimated and the effect of the association of signalling molecules with lipid
      rafts is demonstrated. These results are used to suggest some novel hypotheses on
      BcR-mediated B-cell activation.

PMID- 16983834
TI  - [Post-tonsillectomy hemostasis: a prospective, randomized, double-blind study
      comparing argon beam coagulation and monopolar electrocoagulation].
AB  - BACKGROUND: Argon Beam Coagulation (ABC) enables effective hemostasis and limited
      penetration depth of the coagulation zone. OBJECTIVE: This prospective,
      randomized, double-blind study compares ABC and monopolar electrocoagulation for
      post-tonsillectomy hemostasis. METHODS: Fifty patients undergoing elective
      tonsillectomy were enrolled into the study. Final hemostasis was achieved using
      ABC in one fossa and electrocoagulation in the other fossa, with the sides chosen
      at random. Postoperative bleeding, postoperative pain and the healing of the
      tonsillar fossa were compared for both methods. RESULTS: No differences in any of
      the outcome measures were found between the two methods. ABC was felt to be
      faster and more comfortable than monopolar electrocoagulation. CONCLUSION: ABC is
      an effective and comfortable method for post-tonsillectomy hemostasis.

PMID- 16983835
TI  - [Facial nerve decompression].
AB  - Facial nerve palsy is usually managed conservatively, but in some cases may
      require surgical intervention. In cases in which the continuity of the nerve is
      not disrupted, decompression is the procedure of choice. No reports were found in
      the literature addressing this group separately. We report the results of 33
      facial nerve decompressions conducted in the Sheba Medical Center through the
      years 1985-2002. Fifteen of our patients were operated on using the middle
      cranial fossa approach, 12 underwent mastoidectomy and 6 were treated using the
      combined middle cranial fossa mastoidectomy approach. Twenty-four (72.7%)
      underwent surgery for temporal bone fracture and the rest (27.3%) due to other
      reasons (iatrogenic injury, infection). The postoperative results were determined
      using the House-Brackmann (HB) scale. Patients who were operated on more than 30
      days after complete palsy achieved better results than those operated on earlier
      than 30 days. The total average HB score was 3.2. The followup results are
      significantly worse in patients after less than 3 months, as compared to those
      with 3 to 12 months followup. On the basis of our experience, facial nerve
      decompression achieves good functional results. We found no advantage in early
      vs. late intervention with regard to results. The final results can be determined
      only a year after surgery.

PMID- 16983836
TI  - [Hemostasis and bleeding control in thyroid surgery using electrothermal system
      (Ligasure): our experience in 317 patients].
AB  - BACKGROUND: Intraoperative bleeding during thyroidectomy can cause hemodynamic
      shock and even death. Efforts to control bleeding may prolong the operation and
      put at risk adjacent organs. Postoperative bleeding sometimes requires
      reoperation, and may prolong the hospitalization and the recovery period. There
      are different ways of achieving hemostasis-ligations, sutures, clips and
      coagulation methods. Ligasure is an electrothermal sealer, which seals vessels
      using physical pressure and electric bipolar coagulation. The device has been
      used in thyroid surgery in recent years. AIM: To describe the advantages and
      disadvantages in the use of Ligasure in the light of our experience and in the
      literature. METHODS: (1) Retrospective review of 317 patients who underwent
      thyroidectomy, using Ligasure, in the period 2002-2005. (2) Summary of research
      results in which Ligasure was used. RESULTS: In the 317 operations there were no
      bleeding events nor was there any thermal damage to the recurrent laryngeal
      nerve. The use of Ligasure did not extend the operative duration or the rate of
      complications of recurrent laryngeal nerve palsy or hypo-parathyroidism.
      CONCLUSION: The use of Ligasure is effective in the prevention of operative
      bleeding in thyroid surgery, and it does not prolong the operative time nor raise
      the rate of complications. In comparison with other sealing methods we found
      Ligasure to be the most effective. The main disadvantage of Ligasure is its cost.
      We recommend the use of Ligasure in thyroid surgery.

PMID- 16983837
TI  - [Safe extraction of an impacted open safety pin from the esophagus: a new
      technique and five case studies].
AB  - Esophageal foreign bodies are common, especially in children less than 5 years
      old. However, the presence of an open safety pin in the esophagus is quite rare.
      When this occurs, immediate removal of the safety pin is recommended due to its
      propensity to pierce the esophagus and surrounding structures causing severe and
      sometimes even lethal complications. Between the years 1990 and 2003, fifteen
      infants were referred to the Department of Otolaryngology-Head and Neck Surgery
      at the Rambam Health Care Campus with a history of safety pin ingestion. Plain
      neck, chest and abdomen radiographs showed the presence of an open safety pin
      impacted in the esophagus and pointing upwards in nine of the cases, and in the
      remainder (six infants) a closed pin was demonstrated in the stomach or in the
      duodenum. This report focuses on five cases in which during esophagoscopy only
      the clasp of the safety pin was visible, whereas the sharp point was impossible
      to be grasped, as it seemed to be stuck in the mucosa of the esophagus. In these
      cases the pin was pushed into the stomach, where it was closed, and then it was
      pulled outside without any harm to the mucosa or the gastric and esophageal
      walls. We present a new technique on how to safely close an open safety pin in
      the stomach and remove it, without any complications, using a flexible endoscope.

PMID- 16983838
TI  - [Foreign body aspiration in children: ten-years experience at the Ha'Emek Medical
      Center].
AB  - INTRODUCTION: Foreign body aspiration is common in young children. Delay in
      treatment may lead to complications and an emergency bronchoscopy must be
      performed in suspicious cases. Prevention is the most critical element needed to
      reduce this morbidity. PURPOSE: To examine the demographic data of children at
      high risk of foreign body aspiration in order to develop precautionary measures
      oriented to this population. METHODS: A retrospective review was prepared of all
      the charts of children under 16 years old who underwent bronchoscopy for
      suspected foreign body aspiration in Ha'Emek Medical Center during the period
      1994-2004. RESULTS: The review presented a total of 136 children who had
      undergone bronchoscopy. Foreign bodies were found in 73% of the cases. Two thirds
      of the patients were male and two thirds were children less then two years old.
      The incidence of bronchoscopies that were positive for foreign bodies was higher
      in children less then two years old (82.6%) compared with older children (57.1%),
      p = 0.001. The incidence of Arab children was higher when compared to Jewish
      children and significantly higher than their percentage in the general child
      population (p = 0.001). The rate of bronchoscopies was 11 procedures per 100,000
      children per year. In the majority of cases food was aspirated (82%) especially
      nuts and seeds. CONCLUSIONS: We found that children under the age of two years,
      male children and Arab children were at the highest risk of foreign body
      aspiration. Nuts and seeds are particularly dangerous and it is recommended to
      prevent young children from eating them. Well-defined public education programs
      should achieve prevention.

PMID- 16983839
TI  - [Fiberoptic endoscopic evaluation of swallowing--the Tel Aviv Voice and
      Swallowing Disorders Clinic].
AB  - Fiberoptic endoscopic evaluation of swallowing (FEES) involves passing a
      fiberoptic laryngoscope transnasally to visualize the hypopharynx, larynx, and
      proximal trachea in order to assess swallowing disorders. FEES has been compared
      with the modified barium swallow (MBS) (the presumed "gold standard"). To date,
      reports have demonstrated that FEES is as sensitive as, or even more sensitive,
      for use as a tool in swallowing assessment compared with the MBS. FEES provides
      the clinician with a safe, portable, effective, and valid means of evaluating
      individuals with swallowing disturbances. FEES allows the examiner to identify
      swallowing physiology, determine the safest and least restrictive level of oral
      intake, implement appropriate compensatory techniques, and identify a dysphagia
      rehabilitation plan. In this article we present the Tel-Aviv Voice and Swallowing
      Disorders Center experience. Out of 100 patients that were referred to our center
      for swallowing evaluation 97 patients underwent 102 FEES examinations. Three
      patients couldn't tolerate the examination. In 63% of the patients swallowing
      pathology was found. FEES were performed by teamwork involving a speech-language
      pathologist and otolaryngologist collaborating together thus optimally managing
      the individual with dysphagia safely and efficiently.

PMID- 16983840
TI  - [The effect of steroid therapy on post adenotonsillectomy recovery].
AB  - BACKGROUND: Previous studies on dexamethasone's antiemetic and antinflammatory
      potential in patients undergoing adenotonsillectomy have produced conflicting
      results. OBJECTIVES: To determine the effect of intraoperative I.V. single dose
      dexamethasone on recovery and complications after adenotonsillitis while
      anesthesia techniques, surgical techniques and perioperative treatment are
      standardized. DESIGN: Prospective randomized, controlled study. METHODS: A total
      of 230 patients aged 2-16 years undergoing elective adenotonsillectomy enrolled
      in the study. Patients were randomly assigned to receive i.v. dexamethasone 0.5
      mg/kg (study group), or no treatment (control group). Pain score, emesis, oral
      intake and bleeding were assessed on the first and tenth postoperative day.
      RESULTS: Overall, 204 completed the study, 101 in the study group, 103 in the
      control group. It was found that intraoperative single I.V. dexamethasone
      significantly reduces emesis during the first postoperative day (P < 0.0001),
      significantly reduces pain score on the first (P < 0.0001), and tenth
      postoperative day (P = 0.053), significantly increases the number of patients
      returning to soft diet on the first postoperative day (P = 0.0002) and normal
      diet on the tenth postoperative day (P < 0.0001). No significant difference in
      bleeding tendency between the two groups was noted (P = 0.7202). CONCLUSIONS:
      Intraoperative injection of I.V. dexamethasone 0.5 mg/kg effectively reduced post
      adenotonsillectomy morbidity.

PMID- 16983841
TI  - [Peer review--is there a better system?].

PMID- 16983842
TI  - [The guidelines for the diagnosis prevention and treatment of type 2 diabetes
      mellitus--2005].
AB  - The incidence and prevalence of diabetes have reached epidemic proportions
      worldwide. The reasons for the pandemic are the sharp rise in obesity, decline in
      physical activity and the increase in life expectancy. There are some 400,000
      people with diagnosed diabetes in Israel and they are at a markedly increased
      risk for cardiovascular disease, blindness, end-stage renal disease and lower
      limb amputation. To effectively lower this significantly increased burden of
      disease, a comprehensive multidisciplinary approach to chronic disease management
      is required. To facilitate such an approach, the Israel Diabetes Association
      published a guideline for the diagnosis, prevention and treatment of diabetes.
      The guideline, based on the ADA (American Diabetes Association) and IDF
      (International Diabetes Federation) guidelines, was approved by other national
      professional societies including hypertension, family practice, obesity,
      nephrology, atherosclerosis and internal medicine. The guidelines highlight the
      metabolic syndrome and prediabetic states, interventions for the prevention of
      diabetes, the new definitions of diabetes and impaired glucose metabolism and the
      newly defined targets for glucose, lipid, cholesterol and blood pressure control.
      In addition, the recommendations for periodic review and screening for
      complications are summarized. The need for patient education and empowerment are
      emphasized as is the need for the development and implementation of unique tools
      including computerized treatment flow-charts, prompts and quality measures, for
      the long term management of a complex metabolic disease.

PMID- 16983843
TI  - [The reviewers' review].
AB  - Peer review is a process designed to ensure quality, integrity and novelty of
      scientific or medical studies, published in scientific journals. This process
      accompanies scientific publication since it began and is the cornerstone of
      scientific appreciation and acceptance. Since peer review is a non-transparent
      process and lacks standardized criteria for evaluation, it thereby attracts
      extensive criticism, as discussed in this article. Editors and reviewers of this
      journal have a special responsibility when discussing a submitted article, since
      this journal is the only scientific-medical platform in the Hebrew language.

PMID- 16983844
TI  - [The doctor as a key figure in observing and helping children who were victims of
      sexual abuse in the family].
AB  - Pediatricians and family doctors play an important role in locating and
      diagnosing children at risk, particularly children who are subject to sexual
      abuse and exploitation at the hands of family members. This paper discusses the
      importance of this outside assistance; as such children are often dependent on
      the very person who is abusing them. The article presents disturbing findings
      from previous research, showing that doctors who have suspicions that such abuse
      is taking place do not always report their suspicions to the authorities. This
      paper reviews the range of this phenomenon and spells out the difficulty of
      studying the subject. Details are provided of the severe effects of familial
      sexual abuse on children, both in the short term and in the long term. The
      physical symptoms and other problems of the victims are described, emphasizing
      the responsibility of doctors who come into contact with children and youngsters
      to be aware of this possibility and actively search for cases of sexual
      exploitation. The article also discusses aspects of treatment, advising doctors
      who encounter this problem on ways of dealing with it.

PMID- 16983845
TI  - [Renal vein thrombosis--renal colic with unusual course].
AB  - Although renal vein thrombosis (RVT) is a complication of various renal and
      medical conditions, nephrotic syndrome is known as the most frequent one. RVT in
      patients suffering from nephrotic syndrome is rarely present with flank pain.
      Most patients are asymptomatic and recover spontaneously. The treatment of RVT
      consists of handling the primary condition and treating the thrombosis itself by
      anticoagulation. In severe cases with grave prognosis thrombolytic therapy is
      needed. This is a case study of a 38 year old male who presented with severe
      renal colic which subsequently diagnosed as RVT complication of the nephrotic
      syndrome. The article also reviews the literature regarding the frequency,
      etiological factors, pathophysiology, radiological diagnosis and disease
      treatment.

PMID- 16983847
TI  - [Gossypiboma?].
AB  - Although not a rare finding in medicine and particularly in surgery, only few
      know what "gossypiboma" actually means. The author briefly describes a patient
      found to have a neglicted, missed, surgical gauze in his abdominal cavity and
      explains the origin of the terms.

PMID- 16983846
TI  - [The sense of taste].
AB  - The taste sense is one of the five human senses. It is essential to our survival
      because it enables the individual the choice of correct food, which, in turn, is
      crucial for one's existence, maintenance and function. This is a complicated
      chemical sense, which operates in conjunction with other senses such as vision,
      smell and touch, and is also associated with the operation of temperature and
      consistency receptors. There are five basic tastes: bitter, sweet, sour, salty
      and "fleshy" (umami), each of which has a role in food selection, being
      responsible for the recognition of certain chemicals, which may be either
      necessary or dangerous to our body. The taste cell is located in the taste buds,
      which, in turn, are situated in the tongue, oral cavity and the proximal third of
      the esophagus. This translates the chemical signal of tastants in food to
      electrical stimulation that transfers the signal to higher processing centers in
      the brain, in a process called transduction, which is explained in this review.
      Disturbances in the taste sense, as well as effects of industrial exposure on
      this sense are also described. The accumulated knowledge about the taste sense
      might enable future breakthroughs in the processed food industry.

PMID- 16983848
TI  - [Clinical discussions of internal medicine residents, Sheba, Tel Hashomer,
      November 8th, 2005].

PMID- 16983849
TI  - [The history of the speckled monster].
AB  - It demolished 3 empires, killed princess and peasants indifferently, blinded its
      victims and scarred them for life, changed the outcome of military conflicts and
      eventually induced the discovery of the vaccination technique. Although conquered
      in the late seventies of the 20th century, the spirit of "the speckled monster"-
      smallpox as it was called due to its coetaneous manifestation and high death
      rate, still roam the earth as a bioterrorist threat. From China to Turkey, from
      England to the U.S.A., smallpox plague history traverses nations and physicians.
      This paper discusses the history of the disease and brings forward some of the
      less famous characters who contributed to the eradication of smallpox.

PMID- 16983850
TI  - So hard to care...critical care nursing in Hellas.

PMID- 16983851
TI  - Managing today's reality of delivering critical care nursing.

PMID- 16983852
TI  - Reflection on a patient's airway management during a ward-based resuscitation.
AB  - BACKGROUND: The bag-valve-mask (BVM) system is a common adjunct used during adult
      resuscitation to ventilate the lungs and deliver oxygen to patients in
      cardiopulmonary arrest. Gastric inflation, regurgitation and aspiration are well
      documented complications of BVM ventilation, which can have serious consequences
      for patients. AIM: The aim of this paper is to review the cause of gastric
      inflation, regurgitation and aspiration during BVM ventilation and to consider
      techniques that have been suggested to reduce these problems. METHOD: Using a
      reflective model, the author revisits an actual cardiac arrest, and within a
      structured framework considers the event itself, the context of the event and
      looks at ways in which practice could be improved in future. RESULTS: It is clear
      from the evidence that a reduction in peak airway pressure can reduce the risk of
      gastric inflation, regurgitation and aspiration. A review of the available
      research strongly suggests that in expert hands, the most effective means of
      reducing peak airway pressure is by reducing tidal volume by using a smaller bag.
      CONCLUSION: Although the evidence, as presented, for a reduction in bag size is
      convincing, there appears to be a problem that less regular users do not appear
      to be able to produce effective tidal volumes when using a smaller bag. If a
      reduced bag size is standardized, further research using a diverse group of
      health care workers with the BVM is required before a clear policy can be
      achieved. It is likely that training and practice will be shown to be important
      for nursing staff expected to use the smaller BVM.

PMID- 16983853
TI  - The effect of music listening on older adults undergoing cardiovascular surgery.
AB  - The purpose of this study was to determine the effect of music listening on
      postoperative anxiety and intubation time in patients undergoing cardiovascular
      surgery. Coronary artery disease and valvular heart disease affect approximately
      15 million Americans and 5 million persons in the U.K. annually, with the
      majority of these patients being older adults. The anxiety experienced before,
      during and after surgery increases cardiovascular workload, thereby prolonging
      recovery time. Music listening as a nursing intervention has shown an ability to
      reduce anxiety. The study used a randomized control trial design. Sixty adults
      older than 65 years were randomly assigned to the control and the experimental
      groups. The experimental group listened to music during and after surgery, while
      the control group received standard postoperative care. The Spielberger State
      Trait Anxiety Inventory was administered to both groups before surgery and 3 days
      postoperatively. The mean of the differences between scores was compared using
      analysis of variance. Differences in mean intubation time were measured in both
      groups. Older adults who listened to music had lower scores on the state anxiety
      test (F = 5.57, p = .022) and had significantly fewer minutes of postoperative
      intubation (F = 5.45, p = .031) after cardiovascular surgery. Older adults
      undergoing cardiovascular surgery who listen to music had less anxiety and
      reduced intubation time than those who did not.

PMID- 16983854
TI  - Correcting arterial blood gases for temperature: (when) is it clinically
      significant?
AB  - Interpreting arterial blood gases (ABGs) is a common practice in intensive care
      units. The use of the temperature correction facility, however, is not
      standardized, and the effects of temperature correction on the ABG result may
      affect the overall management of the patient. The aim of this study was to
      discuss the significance of temperature correction. Current practice in the UK
      and Australia is discussed along with a review of physiological principles of
      oxygenation and acid-base balance. The alpha-stat and pH-stat methods of blood
      gas analysis are presented, with arguments for and against using the temperature
      correction facility for blood gas analysis. The study concludes with
      recommendations for practice.

PMID- 16983855
TI  - Critical care outreach 1: an exploration of fundamental philosophy and
      underpinning knowledge.
AB  - Critical care outreach (Outreach) is central to the effective management of
      critically ill patients. Its recent, expedited and somewhat uncoordinated
      introduction has, however, resulted in a lack of understanding about the
      fundamental philosophical theories and sources of knowledge that underpin it.
      Furthermore, there is a lack of understanding of the context in which these are
      applied. It is important that we understand and are able to provide sound
      rationale and guidance for current and future Outreach practice, for the
      education of practitioners and in order to evaluate and show the impact of
      Outreach on patient care. The need for this is heightened in the context of
      current changes in roles and role boundaries, in which there are significant
      pressures and expectations from organizations for Outreach teams to demonstrate
      their effectiveness. The authors argue that the complex situations encountered
      and managed by Outreach are not amenable to traditional forms of measurement and
      that its impact on patient care is, therefore, not readily acknowledged by those
      external to the service. This study explores the philosophical underpinnings and
      types of knowledge inherent in the practice of Outreach. In doing so, it
      illuminates how they apply and contribute to the practice and impact of Outreach.

PMID- 16983856
TI  - Critical care outreach 2: uncovering the underpinning philosophy and knowledge
      through collaborative reflection.
AB  - Critical care outreach (Outreach) was introduced as part of a government strategy
      to address increasing demands on limited intensive care (level 3) and high
      dependency (level 2) resources. The discipline of Outreach developed rapidly and,
      as a result, the fundamental philosophical theories and sources of knowledge that
      underpin its practice remain, at least to some extent, unexplored, and their
      contribution to practice overlooked. It is important that we understand these
      philosophical theories and sources of knowledge so that we are able to provide
      sound rationale and guidance for practice and address the increasing pressure to
      demonstrate effectiveness. The authors argue that the complex situations
      encountered and managed by Outreach are not entirely amenable to traditional
      forms of measurement, and that its impact on patient care is, therefore, not
      readily acknowledged. In applying a model of collaborative reflection, this study
      analyses the management of a clinical case by a nurse consultant in Outreach. In
      doing so, it explores the realities of practice by deconstructing the complexity
      of a particular situation and highlights the variety of knowledge that
      contributes to effective Outreach practice.

PMID- 16983857
TI  - Environmental and occupational health: a "critical science".

PMID- 16983858
TI  - Avian flu from an occupational health perspective.
AB  - Although a pandemic scenario necessarily involves a situation in which a large
      number of people become infected in a nonoccupational setting, past infectious
      disease events have highlighted the unique role that occupational exposure may
      play in the emergence of disease in humans. While small-scale poultry farmers
      have already demonstrated their high risk of exposure and subsequent infection
      with H5N1 avian flu, other bird handling occupations may also be at high risk. In
      this review article, the author highlights the occupational health aspects of a
      newly emerging infectious disease, H5N1 avian flu, and the efforts being made by
      various authorities to confront the possibility of the next flu pandemic. Various
      measures potentially available to protect high-risk workers are outlined,
      emphasizing a hierarchy of controls in which these measures can be placed. The
      author postulates that, by reducing the risk of transmission of avian flu to
      these workers, occupational medicine can play a pivotal role in the world's
      effort to prepare for a pandemic, and may be uniquely positioned to contribute to
      the effort to delay or even avert the emergence of the next pandemic.

PMID- 16983860
TI  - Dermatitis in the mining industry: incidence, sources, and time loss.
AB  - Occupational skin diseases and disorders are the most commonly reported nontrauma
      related category of occupational illness in the United States, and mining has one
      of the highest incidence rates among all industries. The authors' objective in
      this study was to describe mining industry dermatitis incidence, sources of
      exposure, and resultant time lost from work. The authors reviewed Mine Accident,
      Injury and Illness Reports. From 1983 to 2002, the Mine Safety and Health
      Administration reported 975 cases of dermatitis in mines across the United States
      and its territories. Average annual incidence was 14.4 cases per 100 000
      employees. Upper extremities and multiple body regions were most commonly
      involved. Twenty-five percent of miners with dermatitis lost at least 1 day of
      work. Exposure to plants, trees, and vegetation accounted for 24% of all cases. A
      greater understanding of this condition will assist health professionals in
      focusing on appropriate intervention strategies to reduce the occurrence of
      dermatitis and its associated morbidity in mine workers.

PMID- 16983859
TI  - Report of workshop on traffic, health, and infrastructure planning.
AB  - Recent air pollutant measurement data document unique aspects of the air
      pollution mixture near roadways, and an expanding body of epidemiological data
      suggests increased risks for exacerbation of asthma and other respiratory
      diseases, premature mortality, and certain cancers and birth outcomes from air
      pollution exposures in populations residing in relatively close proximity to
      roadways. The Workshop on Traffic, Health, and Infrastructure Planning, held in
      February 2004, was convened to provide a forum for interdisciplinary discussion
      of motor vehicle emissions, exposures and potential health effects related to
      proximity to motor vehicle traffic. This report summarizes the workshop
      discussions and findings regarding the current science on this issue, identifies
      planning and policy issues related to localized motor vehicle emissions and
      health concerns, and provides recommendations for future research and policy
      directions.

PMID- 16983861
TI  - Indoor air pollution in rural China: cooking fuels, stoves, and health status.
AB  - Solid fuels are a major source of indoor air pollution, but in less developed
      countries the short-term health effects of indoor air pollution are poorly
      understood. The authors conducted a large cross-sectional study of rural Chinese
      households to determine associations between individual health status and
      domestic cooking as a source of indoor air pollution. The study included measures
      of health status as well as measures of indoor air-pollution sources, such as
      solid cooking fuels and cooking stoves. Compared with other fuel types, coal was
      associated with a lower health status, including negative impacts on exhaled
      carbon monoxide level, forced vital capacity, lifetime prevalence of chronic
      obstructive pulmonary disease and asthma, and health care utilization. Decreasing
      household coal use, increasing use of improved stove technology, and increasing
      kitchen ventilation may decrease the short-term health effects of indoor air
      pollution.

PMID- 16983863
TI  - Cross-sectional study on occupational noise and hypertension in the workplace.
AB  - To determine whether noise conditions at the workplace are associated with
      hypertension in Japanese male blue-collar workers, the authors analyzed data
      obtained in an annual workplace health examination. Two hundred forty-two workers
      who used ear protectors at their jobs in a paper manufacturing plant served as a
      noisy workplace group, and 173 individuals who worked in a chemical plant
      comprised a nonnoisy workplace group. The prevalence of hypertension was 16.9% in
      the noisy workplace group and 34.7% in the nonnoisy workplace group (p < .01). A
      Mantel-Haenzel analysis showed the difference between the 2 groups to be
      significant. A logistic regression analysis with adjustment for confounding
      factors also showed a significant inverse association between hypertension and
      noise conditions at the workplace (odds ratio = 0.48; 95% confidence interval =
      0.28-0.81). The implementation of guidelines for occupational noise management
      might have contributed to the workers' concern over the prevention of adverse
      health effects caused by workplace noise.

PMID- 16983862
TI  - Respiratory health and indoor air pollution at high elevation.
AB  - In this research, the authors sought to provide experimental data on indoor air
      quality, and the resulting respiratory impact, for a high-elevation (4550 m),
      rural community in Ladakh, India. This community is of interest because the
      primarily nomadic residents burn biomass inside the home for heating and cooking.
      The concentrations of particulate matter (PM), endotoxin, and carbon monoxide
      were determined for 6 homes. Lung function data and induced sputum samples were
      collected for 9 female test-home subjects. In addition, lung function data were
      collected for 84 additional Ladakhi highlanders at this location. Sputum from 3
      visiting scientists (sojourners) was collected and analyzed as well. The average
      PM concentration ranged from 2 mg/m3 to 7 mg/m3, with 85% of the sampled PM sized
      as respirable. The average endotoxin concentration ranged from 2.4 ng/m3 to 19
      ng/m3, and average carbon monoxide levels ranged from 50 ppm to 120 ppm. Lung
      function values for the highlander population and the test-home subjects were
      equal to or greater than predicted, despite the highlanders' significant exposure
      to indoor pollutants. An induced sputum analysis revealed a significantly greater
      total inflammatory cell count (M +/- SD, 10(5) cell/mg) in the Ladakhi natives
      than in the sojourners (107.5 +/- 75.2 vs 7.1 +/- 8.1, p < .01). Although the
      high levels of indoor pollutants did not correlate with significant decrements in
      lung function, the induced sputum analysis revealed marked airway inflammation
      dominated by macrophages and neutrophils. It appears that augmented lung
      mechanics of this high-altitude population are adaptive to reduce the work of
      breathing; thus, decrements in lung function go undetected because the true
      predicted values are greater than expected.

PMID- 16983864
TI  - In the eye of the beholder: rethinking "success" in orthopedic trauma.

PMID- 16983865
TI  - Treatment of femoral shaft fractures in children using the "Tobruk" method.
AB  - The "Tobruk" technique of plaster augmentation of a Thomas' splint can be used
      for the treatment of femoral shaft fractures in children. The radiological and
      clinical data of 118 patients treated using this method were reviewed over a
      consecutive 3-year period. The mean age of the patients was 4.25 years. Mean
      hospital stay was 14.11 days. Mean time spent in the "Tobruk" splint was 44.77
      days. Loss of reduction during splintage occurred in 9.32% of patients. Skin
      complications occurred in 5 patients (4.2%), and cast repairs were necessary in 3
      patients. "Tobruk" splinting is a relatively safe and effective way of treating
      femoral shaft fractures in children. Although its use is not widespread,
      especially in the United States, until better results are achieved with spica
      casting and elastic stable intramedullary nails, it does provide a valid option
      in the treatment of these fractures. A controlled randomized prospective trial
      with long-term follow-up is needed to fully elucidate its value.

PMID- 16983866
TI  - Fixation of unstable distal radius fractures with intrafocal pins and trans
      styloid augmentation: a retrospective review and radiographic analysis.
AB  - Our technique of intrafocal pinning with trans-styloid augmentation is highly
      effective in treating unstable distal radius fractures. In addition, our
      technique is safe and has a minimal number of complications. Although patients
      who are over age 65 may require additional rehabilitation after fracture healing,
      their ultimate outcomes will be satisfactory. Our technique restores radiographic
      parameters, provides excellent fracture reduction, and, most important, leads to
      good functional outcomes.

PMID- 16983867
TI  - Bilateral Galeazzi fracture-dislocations.
AB  - We present the case of a patient with bilateral Galeazzi fracture-dislocations
      with an irreducible distal radioulnar joint (DRUJ) on one side. Current
      treatments, such as anatomic reduction and stable internal fixation of the radius
      and anatomic and stable reduction of the DRUJ followed by plaster immobilization
      in supination, have produced results much better than those associated with
      historical conservative treatments. The most important part of successful
      treatment is maintaining intraoperative control of reduction quality, DRUJ
      stability, and, if necessary, open reduction of the DRUJ. Here we describe the
      surgical technique and present the rare case of a DRUJ being irreducible because
      of interposition of the extensor carpi ulnaris tendon.

PMID- 16983868
TI  - Tethered lateral patellar dislocation as a complication after Galeazzi procedure.

PMID- 16983869
TI  - Lisfranc joint injuries: diagnosis and treatment.
AB  - Injuries to the tarsometatarsal or Lisfranc joint, though rare, are often
      undiagnosed or inadequately treated, resulting in poor long-term outcomes.
      Clinical and radiographic data are needed to recognize and treat these injuries
      for optimal outcomes. In this article, we review the anatomy, biomechanics,
      injury mechanisms, clinical presentation, radiographic evaluation, injury
      classification, treatment, outcome, and complications of Lisfranc joint injuries.

PMID- 16983870
TI  - New enforcement environment affects healthcare.

PMID- 16983871
TI  - Makers of angiogenesis in breast cancer.

PMID- 16983872
TI  - Instrumentation and analytical methods.

PMID- 16983873
TI  - Design of lean work cells: a lean lab layout (part II).

PMID- 16983874
TI  - Efficient laboratory design.

PMID- 16983876
TI  - At bioMerieux, a family's history melds with microbiology's future. The Merieux
      mantle is again passed.

PMID- 16983875
TI  - CLSI evaluation protocols.

PMID- 16983877
TI  - Testing controversy highlights CLIAC's June gathering.

PMID- 16983879
TI  - How and why to start in-house phlebotomy training.

PMID- 16983878
TI  - Recruiting for the future of the clinical laboratory.

PMID- 16983880
TI  - Liability for inadvertent arterial draws.

PMID- 16983881
TI  - Machine creation.

PMID- 16983882
TI  - Interactive tabletop exhibits in museums and galleries.

PMID- 16983883
TI  - Augmenting holograms.

PMID- 16983884
TI  - Broadening our collaboration with design.

PMID- 16983885
TI  - Interacting with digital tabletops.

PMID- 16983886
TI  - Integrating point and touch for interaction with digital tabletop displays.

PMID- 16983887
TI  - Informing the design of direct-touch tabletops.

PMID- 16983888
TI  - TViews: an extensible architecture for multiuser digital media tables.

PMID- 16983889
TI  - Identity-differentiating widgets for multiuser interactive surfaces.

PMID- 16983890
TI  - Mediating group dynamics through tabletop interface design.

PMID- 16983891
TI  - A spectral color analysis and colorization technique.

PMID- 16983892
TI  - Fast volume preservation for a mass-spring system.

PMID- 16983894
TI  - Rosacea: wonderings of a clinician.

PMID- 16983893
TI  - Getting to the point...?

PMID- 16983895
TI  - Aquatic antagonists: stingray injury.

PMID- 16983896
TI  - What is your diagnosis? Lichen simplex chronicus.

PMID- 16983897
TI  - Update on rosacea pathogenesis and correlation with medical therapeutic agents.
AB  - The pathogenesis of rosacea is poorly understood, though clinical features of the
      disease are well-recognized. This article updates current views on mechanisms
      potentially associated with rosacea. Although data is limited, correlation with
      therapies is reviewed.

PMID- 16983898
TI  - Pemphigus foliaceus: a case report and short review.
AB  - Pemphigus foliaceus (PF) is a rare autoimmune blistering disease presenting in
      endemic and sporadic forms. The typical presentation is recurrent shallow
      erosions in a seborrheic distribution. We present a case of a 58-year-old woman
      with PF who was successfully treated with a combination of oral corticosteroids
      and dapsone. We also provide a concise review of the literature and discuss the
      etiology, clinical features, diagnosis, and management of PF.

PMID- 16983899
TI  - Methicillin-resistant Staphylococcus aureus skin abscesses in a pediatric patient
      with atopic dermatitis: a case report.
AB  - Recent trends indicate an increasing incidence of community-acquired methicillin
      resistant Staphylococcus aureus (CAMRSA) in the general population, which is
      especially worrisome for clinicians caring for patients with atopic dermatitis
      (AD). Patients with AD are heavily colonized with S aureus and have impaired skin
      integrity and abnormal immune responses, which predisposes them to more invasive
      cutaneous infections (eg, cellulitis, furuncles, abscesses). In this report, we
      describe a child with severe AD who presented with CAMRSA skin abscesses. The
      presence of an atypical skin infection in patients with AD, particularly those
      unresponsive to conventional penicillinase-resistant penicillins and
      cephalosporins, should alert the clinician to the possibility of MRSA as the
      underlying etiology, and intervention should be directed accordingly.

PMID- 16983900
TI  - Defining criteria used to evaluate response to treatment of acne vulgaris.
AB  - Results from controlled studies form the basis of overall perceptions regarding
      the efficacy and safety of specific treatments. In acne vulgaris, determining
      statistical significance related to mean percentage reduction in inflammatory and
      noninflammatory lesion counts, investigator global assessment, and patient
      (subject) global assessment have formed the basis of most studies. Results may be
      impacted by several mitigating factors related to inclusion and exclusion
      criteria and variations in study "power." Recently, standards for evaluation of
      response to acne treatment have been reconsidered, with new methodologies
      suggested throughout the approval process. For example, the standard of "complete
      clearance" has been introduced. How the new methodologies compare with previous
      standards, and how new criteria will impact the reporting and interpretation of
      trial results are reviewed in this article. Specific study outcomes, including
      those reported in more recent trials with topical adapalene, are utilized as
      illustrative examples.

PMID- 16983901
TI  - Linear unilateral basal cell nevus: a benign follicular hamartoma simulating
      multiple basal cell carcinomas.
AB  - We report a case of linear unilateral basal cell nevus (LBCN) occurring on the
      left lateral neck and left posterior shoulder of a 23-year-old woman. LBCN is a
      rare benign follicular hamartoma that must be distinguished from the more
      aggressive unilateral and segmental variant of nevoid basal cell carcinoma
      syndrome (NBCCS) and the linear variant of BCC.

PMID- 16983902
TI  - Laser and light treatments for pilonidal cysts.
AB  - Pilonidal (nest of hair) cysts are foreign body reactions accompanied by chronic
      inflammation. Current accepted treatments include the traditional conservative
      treatments or aggressive surgery. However, these modalities exhibit a high rate
      of disease recurrence, especially in patients with hirsutism; therefore, affected
      patients often are subjected to repeated surgical interventions. This report
      describes 5 patients treated with either a diode laser or intense pulsed light
      (IPL), which produced results leaving the patients recurrence free. Four of 5
      patients remained recurrence free for 7 months to more than 36 months; one
      patient experienced a recurrence after 36 months, which was longer than his
      previous remission. These results suggest laser and IPL technologies are
      alternatives to traditional surgical intervention, providing potentially longer
      disease-free intervals and fewer recurrences.

PMID- 16983903
TI  - Erythema elevatum diutinum arising in the setting of dermatitis herpetiformis.
AB  - Dermatitis herpetiformis is an autoimmune blistering disease characterized by
      granular deposits of immunoglobulin A (IgA) in dermal papillae. Erythema elevatum
      diutinum is a chronic form of vasculitis associated with IgA paraproteinemia. We
      report a patient with dermatitis herpetiformis who developed characteristic
      erythema elevatum diutinum lesions on the elbows and knees despite sulfone
      therapy. We speculate that the different patterns of IgA deposition in the skin
      account for the clinical manifestation of these 2 uncommon disorders.

PMID- 16983904
TI  - Rheumatoid neutrophilic dermatitis.
AB  - Rheumatoid neutrophilic dermatitis (RND) is an infrequent cutaneous manifestation
      of rheumatoid arthritis (RA). This condition is seen in patients who are both
      positive and negative for a circulating rheumatoid factor. Histologically, it
      presents with a neutrophilic dermatosis, characterized by a heavy dermal
      infiltrate of neutrophils with variable degrees of leukocytoclasis but no
      vasculitis. We describe the case of a young female with seronegative RA who had
      concomitant lesions of RND over both elbows. Her lesions appeared as nodules, but
      RND has been reported as papules and plaques, sometimes with an urticarialike
      appearance or ulcerations. They are often symmetric. The possibility of RND
      should be considered in the differential of unusual skin lesions in all patients
      with RA, as the presentation is quite varied.

PMID- 16983905
TI  - [Set clinical therapeutic guideline in traditional medicine urgently].
AB  - Traditional medicine (TM) has been practiced in China for several thousand years.
      To better standardize the behaviors of medical staff of TM, rapidly improve their
      professional level, effectively and reasonably distribute TM resources, decrease
      the unnecessary application of medical care and suppress the rapidly increasing
      medical expenses, it is necessary to urgently set clinical therapeutic guideline
      in TM under the direction of evidence based medicine (EBM). The article also
      discusses the main existing problems and their solutions in setting clinical
      therapeutic guideline in TM.

PMID- 16983906
TI  - [Joint statement of establishing Chinese clinical trial registration and
      publishing system].

PMID- 16983907
TI  - [Statement for Chinese clinical trial registration and publishing system].

PMID- 16983908
TI  - [Making repeated clinical trials aiming at finding specific indications is the
      way for improving clinical efficacy of traditional Chinese medicine].
AB  - The modern clinical evaluation methods and index system are the tools for
      clinical evaluation in traditional Chinese medical trial, and more importantly
      the prerequisite for approbation of their outcomes. From the view of syndrome
      differentiation theory of traditional Chinese medicine, the previous therapeutic
      process is also a diagnostic process for the following therapeutic course, so to
      make repeated clinical trials aiming at finding specific indications would be one
      of the important ways to improve the clinical efficacy of traditional Chinese
      medicine.

PMID- 16983909
TI  - [Treatment of acute intracerebral hemorrhage with a comprehensive protocol of
      integrated Chinese and Western medicine].
AB  - OBJECTIVE: To observe the effect and safety of a comprehensive protocol of
      integrated Chinese and Western medicine (ICWM) in treating acute intracerebral
      hemorrhage (AICH). METHODS: A multi-center, single blinded, random and control
      clinical trial was adopted with 404 patients with AICH, they were divided into
      the treatment group (199 cases) treated with ICWM protocol, and the control group
      (205 cases) treated with Western medicine plus placebo, and AICH related indexes
      were assessed after treatment. RESULTS: Compared with the control group, the
      neurological deficit score (National Institute of Health Stroke Scale, NIHSS)
      determined on the 28th and the 90th day after treatment was ameliorated in the
      treatment group (P < 0.01). Moreover, the 90th day assessment showed that the
      mortality and severe disability rate was lower (BI < 75) (P <0.05), the complete
      rehabilitation and mild disability rate (BI > or = 95, P < 0.05), and the
      sociability rate (Functional Assessment Questionnaire, FAQ) were higher (P <
      0.01) in the treatment group than those in the control group. The incidence of
      adverse reaction was 5.53%, manifested as non-infective diarrhea. CONCLUSION: The
      ICWM protocol used in this study may improve neural function and quality of life
      of AICH patients, and reduce the mortality and severe disability rate in those
      after 90 days' treatment, with only non-infective diarrhea as the adverse
      reaction.

PMID- 16983911
TI  - [Study on TCM syndrome differentiation rules in coronary artery bypass grafting
      patients during peri-operation period].
AB  - OBJECTIVE: To study the TCM syndrome differentiation rules in coronary artery
      bypass grafting (CABG) patients during peri-operation period. METHODS: According
      to the Guideline for Clinical Trail of Traditional Chinese New Drugs and
      experience of Professor DENG Tie-tao, the standard of TCM syndrome
      differentiation for CABG patients was established, with which 161 CABG patients
      were classified before and two weeks after CABG operation. RESULTS: Before CABG,
      the qi stagnation and blood stasis syndrome type was the type most commonly seen
      (46.0%), the next in turn was the phlegm stagnation type (24.8%), the yang-qi
      deficiency type (15.5%), and the yin-blood deficiency type (13.7%). While after
      CABG, the phlegm stagnation syndrome type was the most frequently occurred one
      (35.9%), then in turn was the yang-qi deficiency type (30.8%), the yin-blood
      deficiency type (21.2%) and the qi stagnation with blood stasis type (12.2%).
      CONCLUSION: For patients before CABG, the pathological characteristic is mostly
      the deficiency in root with excess in superficiality, and the commonest syndrome
      is the qi stagnation with blood stasis type. For patients after CABG, both
      deficiency and excess is the pathological characteristic, the Xin-qi and Xin-yang
      deficiency syndrome the commonest type, and with phlegm as the main pathologic
      factor.

PMID- 16983910
TI  - [Clinical observation on effect of tongfu xiere recipe in treating surgical
      abdominal diseases accompanied with systemic inflammatory response syndrome].
AB  - OBJECTIVE: To observe the effect of Tongfu Xiere Recipe (TXR) on surgical
      abdominal diseases accompanied with systemic inflammatory response syndrome
      (SIRS). METHODS: Forty-six patients in the post-operational stage were treated by
      basic therapy, including conventional treatment and antibiotics applying, and
      combined use of TXR, and compared with the 43 patients treated by basic therapy
      alone as the control group. RESULTS: Compared with the control group, the
      incidence of complications in the treatment group was significantly lower
      (P<0.01). The incidence of multiple organ dysfunction syndrome (MODS) and the
      mortality in the treatment group showed an decreasing tendency. Moreover, levels
      of plasma endotoxin, TNF-alpha, IL-6 and IL-8 in the treatment group after
      treatment decreased significantly, while IL-2 level increased (P < 0.01), and
      showed a significant difference (P < 0.01) as compared with those in the control
      group. CONCLUSION: The combined therapy can decrease the levels of blood
      endotoxin and inflammation promoting cytokine and increase the level of cytokine
      that directly related with immune function to regulate immunity and inhibit the
      inflammatory reaction, and furthermore, to prevent MODS and decrease the
      mortality of patients with surgical abdominal diseases accompanied SIRS.

PMID- 16983912
TI  - [Effects of combined therapy of human leucocyte antigen haploidentical related
      bone marrow transplantation and Chinese medicine in treating leukaemia].
AB  - OBJECTIVE: To explore the feasibility of human leucocyte antigen (HLA)
      haploidentical related T-cell undepleted allogeneic bone marrow transplantation
      (Allo-BMT) combined with Chinese medicine for the treatment of leukaemia.
      METHODS: Four patients with chronic myeloblastic leukemia (CML) and 4 with acute
      myeloid leukemia (AML) received allo-BMT with graft from 1 - 3 HLA-mismatched
      related donors. All patients were pre-treated with standardized conditioning
      regimen consisting of high dose Ara-c, cyclophosphamide (CY) and total body
      irradiation (TBI) or busulfan. Donors were given G-CSF 250 microg/d for 7 days
      prior to marrow harvest. To prevent GVHD, besides application of CSA and MTX, ATG
      2.5 mg/kg was given everyday for 4 days before transplantation, and MMF 1.0 g per
      day starting from the 7th day after transplantation. Chinese medicine for
      replenishing qi and yin and strengthening Pi and Wei was administrated orally
      after transplantation. RESULTS: Successful haematopoietic reconstruction was seen
      in all patients. The median days for reaching of granulocyte >0.5 X 10(9)/L and
      platelet > 20 x 10(9)/L were 12 (range 10-14) and 20 (range 18-25) days
      respectively. GVHD of skin in various grade was seen in 7 patients, among whom
      only one advanced to grade IV; besides, 2 accompanied with GVHD of gut, one with
      hemorrhagic cystitis, one died for concurrent infection on the 81st day, and one
      left hospital of his own accord on the 46th day. The median follow-up duration
      was 18 (range 2-32) months, during this period six patients were alive in a
      disease-free situation. CONCLUSION: Combined therapy of HLA haploidentical
      related T-cell undepleted Allo-BMT and Chinese medicine plus immunosuppressants
      with pre-harvest G-CSF application in doner could effectively reduce the
      incidence of acute severe GVHD and raise the disease-free survival rate in
      treating leukaemia.

PMID- 16983913
TI  - [Observation on the effect of zhiling capsule in treating patients with lung
      cancer of middle/advanced stage].
AB  - OBJECTIVE: To observe the effect and safety of Zhiling Capsule (ZC) in treating
      lung cancer of middle/advanced stage. METHODS: With the multi-center, randomized,
      double-blinded and parallel controlled method, the patients were divided into 4
      groups, the 104 patients in the group A were treated with the whole recipe of ZC,
      the 52 in the group B with the disassembled recipe 1 (Western medicines) of ZC,
      the 46 in the group C with the disassembled recipe 2 (Chinese medicines) of ZC,
      and the 48 in the control group with Pingxiao Capsule, all the drugs were
      administered orally for 2 weeks. The changes of syndrome of qi-yin deficiency,
      symptoms, quality of life (QOL), body weight and adverse reactions occurred in
      patients were observed. RESULTS: The effective rate in alleviating syndrome in
      the groups A-D was 91.3%, 80.8%, 37.0% and 14.6% respectively; in remitting
      stuffiness and chest pain 86.9% , 60.5%, 20.0% and 10.0%; in improving appetite
      was 80.4%, 47.9%, 23.7% and 10.3%. QOL in the groups A-C was significantly
      elevated after treatment (P < 0.05 or P < 0.01), the improvement of group A was
      superior to that of other treatments (P < 0.01). Body weight in the group A was
      significantly increased and superior to that of others (P < 0.05). The whole
      recipe of ZC showed the therapeutic effect superior to that of the other
      treatments (P < 0.05). No obvious adverse reaction was found in all the 4 groups.
      CONCLUSION: ZC can improve the symptoms and QOL in patients with lung cancer of
      middle/advanced stage.

PMID- 16983914
TI  - [Effects of shenmai injection on the clinical efficacy of noninvasive ventilation
      in patients with severe respiratory failure caused by chronic obstructive
      pulmonary disease].
AB  - OBJECTIVE: To study the effect of Shenmai Injection (SMI) on the clinical
      efficacy of noninvasive positive-pressure ventilation (NPPV) in treating patients
      with severe respiratory failure (RF) caused by chronic obstructive pulmonary
      disease (COPD). METHODS: Patients in the control group (n=23) were treated with
      conventional therapy plus NPPV, and those in the treatment group (n=25) received
      the same treatment but with intravenous infusion of SMI 30 ml once a day
      additionally. The treatment lasted for 10 days. Arterial oxygen saturation (SaO2)
      was continuously monitored in all patients, arterial blood gas values was
      determined before treatment and at the 6th hour, the 24th hour, the 3rd day and
      the 7th day after treatment, and consciousness, breath, heart rate and severity
      of dyspnea were observed during the treating period. RESULTS: All patients in the
      treatment group were markedly improved and discharged from hospital, while in the
      control group 20 were improved and discharged from hospital, but the other 3
      failed to be remitted and received the conventional invasive mechanical
      ventilation. The duration of hospitalization and ventilation were 11.3 +/- 2.5 d
      and 5.8 +/- 2.8 d in the treatment group, and 13.2 +/- 2.7 d and 7.5 +/- 3.0 d in
      the control group, showing significant difference in the two indexes between the
      two groups (P < 0.05). The dyspnea score and the arterial blood gas values
      determined on the 3rd and 7th day were significantly improved in the treatment
      group than those in the control group (P < 0.05 or P < 0.01). The incidence of
      endotracheal intubation caused adverse reaction, such as facial-skin crush wound,
      abdominal distention and contaminated infection in the treatment group was
      obviously lessened as compared with the control group. CONCLUSION: SMI could
      shorten the duration of hospitalization and mechanical ventilation, reduce
      trachea cannulation, and decrease the incidence of complications and adverse
      reactions in the patients with severe RF due to COPD treated with NPPV.

PMID- 16983915
TI  - [Exploration on the common characters of sub-healthy people based on clinical
      epidemiology].
AB  - OBJECTIVE: To study the common characters of sub-healthy people. METHODS:
      Questionnaire of clinical epidemiological investigation was adopted in the sub
      healthy people. RESULTS: The commonest symptoms and their frequency in sub
      healthy people were fatigue 78.7%, poor quality of sleep 73.4%, amnesia 59.9%,
      fatigue irrelievable after rest 59.1%, dry throat 59.0%, dizziness 58.6%, dry and
      xerotic eyes 58.3%, ache with distension eyes 57.8%, ache 56.4%, early awakening
      52.7%, difficulty in falling asleep 52.5%, irritability 51.8%, etc. The commonest
      risk factors were lack of relaxation 60.4%, lack of physical exercise 58.0%,
      working with frequent extra shifts 56.7%, air pollution 56.2%, noise pollution
      51.3%, etc. The commonest syndrome types in sub-healthy people were insufficiency
      of Pi-qi type 10.2%, Gan-qi stagnation and Pi deficiency type 10.1%, deficiency
      of Xin and Pi type 9.7 %, retention of dampness due to Pi-deficiency type 7.4%
      and qi deficiency type 4.2%, et al. CONCLUSION: The commonest symptoms in sub
      healthy people are fatigue, poor quality of sleep, amnesia, irrelievable fatigue
      after taking rest, dry throat, dizziness, dry and xeritic eyes, ache with
      distension in eyes, ache, early awakening, difficulty in falling asleep,
      irritability, etc. The commonest risk factors are lack of relaxation and physical
      exercise, working with frequent shift, air and noise pollution. The commonest
      syndromes of sub-healthy people are insufficiency of Pi-qi type, Gan qi
      stagnation and Pi deficiency type, deficiency of Xin and Pi type, retention of
      dampness due to Pi deficiency type, qi deficiency type. These provides evidence
      for prevention and treatment of sub-health with TCM.

PMID- 16983916
TI  - [Study on the relationship between TCM syndrome and gastroscopic feature in
      children with stomachache].
AB  - OBJECTIVE: To explore the characteristic of TCM syndrome in children with
      stomachache and its relationship with the gastroscopic feature. METHODS: The
      relationship between macroscopic syndrome differentiation and microscopic
      syndrome differentiation in 300 children with stomachache was analyzed by means
      of clinical syndrome differentiation and gastroscopic examination. RESULTS: The
      total disease detectable rate of gastroscopic examination was 98.3%. Dampness
      heat syndrome and deficiency-cold syndrome were the syndromes that most commonly
      be detected by either macroscopic or microscopic syndrome differentiation. And
      the two methods of differentiation showed better coherence in superficial
      gastritis. CONCLUSION: The clinical effect of TCM therapy on children stomachache
      could be improved through integrative Chinese and Western medical approach, by
      conducting syndrome differentiation referring to the gastroscopic features, which
      could conduct microscopic guidance to the clinical macroscopic syndrome
      differentiation.

PMID- 16983917
TI  - [Mechanism of epimedium flavonoids in regulating immuno-senescence via nuclear
      factor-kappa B related signal transduction pathway].
AB  - OBJECTIVE: To explore the mechanism of epimedium flavonoids (EF) in regulating
      immunosenescence via nuclear factor-kappa B (NF-kappaB) related signal
      transduction pathway. METHODS: (1) The apoptosis index (AI) of splenic lymphocyte
      in aged rats was monitored by flow cytometry, that of young rats was taken as
      control. (2) The differential expression profile of NF-kappaB related signals in
      aged rats allocated in the control group (aged rats, group A), the EF treated
      group (group B), the PDTC (a NF-kappaB inhibitor) treated group (group C) and the
      PDTC plus EF treated group (group D), was determined and the main significant
      molecules in them were analyzed with gene microarray of 96 genes related to NF
      kappaB signal pathway. RESULTS: Excessive apoptosis of T lymphocyte cell was seen
      in aged rats, and it was significantly suppressed in group B and D. In group B,
      73 genes were up-regulated to different extent, including 10 of the NF
      kappaB/Rel/IB gene family, transduction signal molecule member of NIK/IKK/I
      B/Rel/NF-kappaB, NF-kappaB regulatory target genes, trans-membrane receptors,
      transcription factors, and receptor protein, etc. But the up-regulation on NF
      kappaB gene family could not be seen in group C and that on others were also
      alleviated, while in the group D, the NF-kappaB gene family and its related
      transduction pathway were still activated to some extent. The NF-kappaB gene
      family showed a markedly common feature after EF intervention, either used alone
      or in combination with PDTC, i.e. the significant upregulated NF-kappaB1, NF
      kappaB2, Rel B and I Bepsilon, and activated NIK/IKK/I B/Rel/NF-kappaB pathway.
      CONCLUSION: EF can suppress the excessive apoptosis of splenic lymphocyte in aged
      rats and activate Rel/NF-kappaB/ I B/IKK and their signal transduction pathway to
      up-regulate NF-kappaB through adjusting I Bepsilon and I Balpha, which may be the
      essential mechanism of EF in rebuilding the immune homeostasis of T lymphocyte
      apoptosis and retarding immunosenescence.

PMID- 16983918
TI  - [Study on regulatory effect of Bushen Antai Recipe on levels of estrogen and
      progesterone in blastocyst implantation dysfunction mice].
AB  - OBJECTIVE: To investigate the effect and explore the mechanism of Bushen Antai
      Recipe (BAR) on pregnancy rate and number of implantation site in blastocyst
      implantation dysfunction (BID) mice induced by indomethacin. METHODS: Pregnant
      mice were divided into 3 groups randomly: the normal group, the model group and
      the BAR group. Tap water was given orally to the rats in the normal and model
      groups, and BAR to the rats in the BAR group from the first day of pregnancy for
      5 or 8 days; on the 3rd and 4th day dissolvent was injected subcutaneously twice
      per day in the normal group, while indomethacin (4.33 mg/kg) was injected
      subcutaneously twice per day in the other two groups to establish implantation
      dysfunction model; serum estrogen (E) and progesterone (P4) levels were detected
      on the 5th and 8th day; the pregnancy rate and number of implanted site was
      observed and the receptors of E and P4 in endometrium of uterus were examined by
      immunohistochemistry on the 8th day. RESULTS: The pregnancy rate and number of
      implanted site was 27.3% and 5.3 +/- 0.7 respectively in the model group,
      significantly lower than those in the normal group (90.9%, 13.3 +/- 2.8), and the
      BAR group (72.7%, 10.7 +/- 2.2, P < 0.05). Serum E level was higher in the BAR
      group than that in the model group on the 5th and 8th day, and even higher than
      that in the normal group on the 8th day; serum P4 level was lower in the model
      and BAR groups than that in the normal group on the 5th day (P < 0.01), but
      higher in the BAR group than that in the model group on the 8th day.
      Immunohistochemical observation showed that expressions of E and P4 receptor
      increased remarkably in the BAR group than those in the model group. CONCLUSION:
      BAR increases the pregnancy rate and number of implanted site of indomethacrne
      induced BID mice through regulating E and P4 levels and enhancing the expressions
      of their receptors in the endometrium.

PMID- 16983919
TI  - [Changes of ICAM-1 and P-selectin in rats with pulmonary thromboembolism and the
      effect of safflower injection].
AB  - OBJECTIVE: To observe dynamically the expressions of intercellular adhesion
      molecule-1 (ICAM-1) and P-selectin (Ps) in the vascular endothelium in rats with
      pulmonary thromboembolism (PTE) and the effect of Safflower Injection (SI).
      METHODS: Rats were randomly divided into the normal group, the model group and
      the treatment group. PTE model was induced by intravenous injection of auto-blood
      clots, and SI was injected intravenously immediately after modelling with 2
      ml/(kg d) for 5 days to the rats in the treatment group. Animals were sacrificed
      in batches at the 1st, 3rd, 24th, 72nd and 120th h after embolization to observe
      the pathological changes and detect the protein and mRNA expressions of ICAM-1
      and Ps in pulmonary vascular endothelium by immunohistochemistry and in situ
      hybridization respectively. RESULTS: Pathological observation showed obvious
      embolism in pulmonary arteries and inflammatory reaction after modelling, which
      was abated after SI treatment. ICAM-1 and Ps expressions were elevated at the 3rd
      and the 1st h after embolization respectively (both P < 0.01), which also were
      abated in the treatment group. CONCLUSION: SI may alleviate pulmonary injury in
      PTE rats by down-regulating the expressions of ICAM-1 and Ps.

PMID- 16983920
TI  - [Effect of jingui shenqi pill on morphology of injured spinal cell apoptosis in
      rats caused by brachytherapy].
AB  - OBJECTIVE: To study the effect of Jingui Shenqi Pill (JSP) on morphology of
      spinal cell apoptosis in rats injured by 192Ir irradiation. METHODS: One hundred
      and twenty rats were randomly divided into four groups: the model group, the JSP
      group, the prednisone group and the normal group. Corresponding pharmaceutics
      were given to rats once a day for 14 days respectively. Then except rats in the
      normal group, the others received 192Ir interstitial irradiation with the dosage
      of 22 Gy using back-fixing technology. The injured segments of spinal cord were
      taken out for HE staining, TUNEL examination and observation with electron
      microscope 8 hrs, 24 hrs and 4 weeks after irradiation. RESULTS: HE staining
      examination showed no obvious histological change in rats 8 and 24 hrs after
      irradiation, but pathological changes, as tissue rarefaction and hemorrhage did
      found in white matter of spinal cord shown by TUNEL 4 weeks later. Electron
      microscopic examination and TUNEL staining showed that as compared with the model
      group, the apoptotic index in the JSP and predinisone treated groups was
      significantly lower (P < 0.01) 8 hrs after radiation, but it showed insignificant
      difference between groups at the time points of 24 hrs and 4 weeks after
      radiation (P > 0.05). CONCLUSION: JSP could act against apoptosis of gliocyte in
      spinal cord of rats in early stage after brachytherapy, indicating that JSP
      possessing a prednisone-like action.

PMID- 16983921
TI  - [Effect of emodin on NO-cGMP signal pathway in rat vascular endothelium in
      vitro].
AB  - OBJECTIVE: To investigate the vasorelaxation effect of emodin and its
      relationship with NO-cGMP signal pathway. METHODS: Changes of tension of rat
      thoracic aortic rings were measured by MedLab biologic signal collection system,
      and the activity of total nitric oxide synthase (tNOS), constitutive NOS (cNOS)
      and inducible NOS (iNOS) in endothelium after being treated with emodin was
      determined with nitric acid reductase method. RESULTS: Emodin relaxed the
      phenylephrine and potasium chlorate induced contraction of aortic rings, either
      with or without intact endothelium, in a concentration-dependent manner.
      Pretreatment of no-specific potassium channel blocker strontium chloride (CsCL)
      could attenuate the vasorelaxation effect of emodin on aortic rings without
      intact endothelium, but it could not inhibit vasorelaxation of emodin on aortic
      rings with intact endothelium. This vasorelaxation action of emodin (40
      micromol/L) could be partial blocked by NOS inhibitor L-NAME and guanylate
      cyclase inhibitor ODQ, with the vasorelaxation range dropped to 64.76 +/- 13.73%
      and 6.28 +/- 4.79% respectively. Moreover, emodin (40 micromol/L) increased iNOS
      activity significantly. CONCLUSION: The concentration-dependent vasorelaxation
      effect of emodin might act by activating the NO-cGMP pathway in vascular
      endothelium.

PMID- 16983922
TI  - [Effect and mechanism of shenshuai mixture (SM) in promoting repair of kidney in
      acute renal failure rats].
AB  - OBJECTIVE: To dynamically observe the effect of Shenshuai Mixture (SM) on repair
      of kidney in acute renal failure (ARF) rats. METHODS: Male SD rats were divided
      into 4 groups randomly, the normal group, the SM group, the verapamil group and
      the model control group. Except those in the normal group were treated with
      normal saline without modeling, all remaining rats, after being made into ARF
      model by intra-muscular injection of glycerin, were treated with SM, verapamil
      and normal saline respectively via gastrogavage. Renal function, renal pathology,
      mRNA expression of epidermal growth factor (EGF) and protein expression of
      proliferating cell nuclear antigen (PCNA) were detected once every day from the
      1st day to the 5th day. Results (1) BUN and Scr levels increased markedly 24 hrs
      after modeling, but the Scr level in the two treated groups was significantly
      lower than that in the model group (P < 0.05). Compared with that in the model
      group and the verapamil group, renal function was better in the SM group on the
      3rd day (P < 0.01), and approach to normal level on the 5th day. (2) Renal
      pathological changes alleviated in every phase of ARF in the SM group than that
      in the model group, especially part of tubule regeneration could be seen on the
      3rd day (metaphase), and renal structure was rehabilitated on the 5th day
      (convalescence), prior to those in the model group. (3) At the 3rd day expression
      of EGF mRNA and PCNA in tubule epithelial cell (TEC) increased remarkably in the
      SM group, higher than those in the model and verapamil group (P < 0.05).
      CONCLUSION: SM could promote renal tissue regeneration and rehabilitation, and
      shorten the course of ARF through up-regulating mRNA expression of EGF in TEC.

PMID- 16983923
TI  - [Effect of combination of Chinese and Western medicines on sinus rhythm
      maintenance in patients with auricular fibrillation after conversion].
AB  - OBJECTIVE: To investigate the curative effects of irbesartan, amiodarone and
      Wenxin Granule (WG), applied alone or in combination, on sinus rhythm maintenance
      in patients with auricular fibrillation (AF) after conversion. METHODS: Forty-one
      patients of persistent AF, after their fibrillation being converted, were divided
      into three groups randomly, and treated with amiodarone (group A, n=14),
      irbesartan and amiodarone (group B, n=15), and WG plus irbesartan and amiodarone
      (group C, n=12) respectively for 6 months. RESULTS: Compared with that before
      treatment, the inner diameter of atria sinistrum reduced in group B and C, and
      the reduction in the latter was superior to that in the former (P < 0.05); the
      diameter of left ventricle also reduced in group C (P < 0.05); and the
      maintenance rate of sinus rhythm was higher in group C than that in group A (P <
      0.05). CONCLUSION: Combined therapy of Chinese and Western medicines shows
      synergistic effect of anti-arrhythmia.

PMID- 16983925
TI  - [Clinical analysis on high-sensitivity C-reactive protein in hypertensive
      patients with blood-stasis syndrome].
AB  - OBJECTIVE: To study the correlation of serum high-sensitivity protein (hs-CRP)
      level and the clinical score of blood-stasis syndrome as well as the clinical
      indexes in hypertensive patients. METHODS: Levels of serum hs-CRP, blood lipids,
      fasting blood glucose (FBG), body mass index (BMI), left ventricular mass index
      (LVMI), fibrinogen (Fg), urinary albumin (UA), and score of blood-stasis syndrome
      (SBSS) in 117 patients were measured, and the relationship between hs-CRP and the
      other indexes was analyzed. RESULTS: Spearman rank correlation analysis showed
      that hs-CRP level was significantly positively correlated with SBSS, triglyceride
      (TG), FPG, BMI, LVMI, Fg, and UA, while negatively correlated with high density
      lipoprotein cholesterol (HDL-C). CONCLUSION: Hs-CRP is closely related with the
      formation and development of blood-stasis syndrome in hypertensive patients.

PMID- 16983924
TI  - [Retrospective analysis on 116 cases of bradyarrhythmia treated with TCM based
      syndrome differentiation].
AB  - OBJECTIVE: To retrospective analyze the short- and long-term therapeutic effect
      of TCM treatment based on syndrome differentiation on bradyarrhythmia. METHODS:
      Data of 116 patients with bradyarrhythmia treated by TCM based on syndrome
      differentiation from 1995 to 2005 were collected. The changes of clinical
      symptoms and their outcomes as well as the 24h-dynamic cardiogram were evaluated.
      And a 1-5 years follow-up study was conducted to survey the heart rhythm, heart
      rate, drugs applied and artificial cardiac pacemaker (ACP) installation in the
      patients. RESULTS: After 3 months' treatment, the total effective rate was 91.4%.
      During the 1-5 years of follow-up, except 6 patients received ACP installation,
      all the others were alive in stable condition, and no obvious side effect was
      found. CONCLUSION: TCM treatment based on syndrome differentiation has reliable
      and stable therapeutic effects on bradyarrhythmia.

PMID- 16983926
TI  - [Discussion on methods for searching traditional Chinese medical literature in
      English in PubMed-MEDLINE database].
AB  - The methods for searching traditional Chinese medical literature in English with
      subject headings in PubMed-MEDLINE database were discussed from the practical
      view, and seven useful searching methods with free words according to practical
      experiences were put forward in order to assist the domestic TCM researchers to
      utilize PubMed-MEDLINE database in searching overseas TCM literature in English.

PMID- 16983927
TI  - [On the English translation of TCM pulse picture terms].
AB  - At present, the English translation of TCM terms of pulse picture are various,
      which would bring confusion to the study and research on TCM diagnostics. In this
      paper, four principles for the translation are suggested by the authors: to
      distinguish the nomenclature of term with its connotative explanation, to
      translate with commonly used words in general, to create new word with common
      affix and to differentiate the terms similar in meaning. The authors tried to
      make choice the best translation for each kind pulse picture, and explained the
      reasons for selection.

PMID- 16983928
TI  - [Progress of therapeutic research on cardiovascular and cerebrovascular diseases
      with chrono-medicine].
AB  - Comformed with the natural biological universal view of "harmony of human and
      nature", the clinical and experimental researches and the achievements on chrono
      medicine for cardiovascular and cerebrovascular diseases in recent 10 odd years
      were analyzed and summarized, and the problems in the current researches and the
      stressed spots of the future research were put forward in this paper.

PMID- 16983929
TI  - Relationship of peritoneal transport rate and dialysis adequacy with inflammation
      in peritoneal dialysis patients.
AB  - Inflammation, dialysis adequacy, and peritoneal transport rate (PTR) influence
      clinical outcomes in peritoneal dialysis (PD) patients. The present study
      examined the relationship of C-reactive protein (CRP), a marker of inflammation,
      to PTR and residual renal function (RRF) in PD patients. We recorded the baseline
      dialysate-to-plasma creatinine (D/P Cr) of 210 PD patients starting in 1986. In a
      subgroup of 42 patients, we serially measured high-sensitivity CRP levels
      and.dialysis adequacy, including weekly Kt/V urea and creatinine clearance (CCr),
      starting in May 2003. The patients were followed to January 2006. Mean age was 53
      +/- 16 (standard deviation) years, and 70% of the patients were African American.
      Enrollment mean and median CRP levels were 13.53 +/- 20.8 (range: 0.2-95.8) and
      7.15 mg/L respectively. Mean weekly residual CCr and Kt/V during follow-up were
      7.11 +/- 15.47 L/1.73 m2 and 0.14 +/- 0.30 respectively. The mean enrollment D/P
      Cr was 0.649 +/- 0.12 (range: 0.429-0.954). Patients with CRP > 10 mg/L had
      significantly lower weekly residual CCr (0.59 L/1.73 m2 vs. 10.1 L/1.73 m2, p =
      0.01), residual Kt/V (0.01 vs. 0.20, p = 0.01), total CCr (56 L/1.73 m2 vs. 62
      L/1.73 m2, p= 0.047), and total Kt/V (2.09 vs. 2.49, p = 0.001) than did those
      with CRP < or = 10 mg/L. Levels of CRP correlated negatively with weekly residual
      CCr (r = -0.42, p = 0.006), residual Kt/V (r = -0.43, p = 0.006), and total Kt/V
      (r = -0.44, p = 0.004). Enrollment D/P Cr was inversely correlated with serum
      albumin (r = -0.24, p = 0.001) and directly correlated with peritoneal protein
      loss (r = 0.34, p = 0.028). Higher enrollment D/P Cr was associated with lower
      observed cumulative survival (Kaplan-Meier) in PD patients. However D/P Cr was
      not an independent predictor of long-term survival in PD patients. Using
      multivariate Cox regression analysis, and including D/P Cr and residual Kt/V in
      the model, enrollment CRP was an independent predictor of mortality (relative
      risk = 1.036, p = 0.018). We conclude that elevated CRP is associated with lower
      RRF As a predictor of mortality, CRP may be better than RRF and D/P Cr.

PMID- 16983930
TI  - Inhibition by mercuric chloride of aquaporin-1 in the parietal sheep peritoneum:
      an electrophysiologic study.
AB  - The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis.
      In this study, we used Ussing-chamber experiments to investigate the effect of
      HgCl2, an aquaporin-1 inhibitor, on the transmesothelial electrical resistance
      (RTM) of isolated sheep parietal peritoneum. Peritoneal samples from the
      diaphragm of adult sheep were isolated immediately after the death of the animal
      and were transferred within 30 minutes to the laboratory in a cooled Krebs-Ringer
      bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O(2)/5% CO2. A planar
      sheet of the parietal peritoneum was mounted in an Ussing-type chamber and HgCl2
      (10(-4) mol/L) was added apically or basolaterally. The RTM was measured before
      and serially after the addition of the HgCl2. The entire experimental apparatus
      was held at 37 degrees C, because active ion transport is temperature-dependent.
      The results presented are the mean +/- standard error of 12 experiments. The
      control RTM (that is, before the addition of HgCl) was 19.3 +/- 0.38 omega x cm2.
      Addition of HgCl2 apically induced a decrease in the RTM to 16.25 +/- 0.86 omega
      x cm2 within 1 minute. When added basolaterally, HgCl2 action was similar, with a
      rapid reduction in the RTM to 18.1 +/- 0.51 omega x cm2 (p < 0.05). A clear
      association between the RTM and the active transmesothelial ion transport was
      shown in previous studies. In the present study, rapid action of HgCl2 on the
      permeability ofthe parietal peritoneum was observed, resulting in a reduction in
      the RTM Taken together, these findings indicate that inhibition of aquaporin-1
      alters the ionic permeability of the parietal peritoneal membrane.

PMID- 16983931
TI  - Early estimation of high peritoneal permeability can predict poor prognosis for
      technique survival in patients on peritoneal dialysis.
AB  - At the beginning of continuous ambulatory peritoneal dialysis (CAPD), different
      patients exhibit large differences in peritoneal permeability. To determine if
      early estimation of peritoneal permeability can predict the prognosis of CAPD, we
      used data from a personal dialysis capacity (PDC) study group in Japan to
      investigate patient and technique survival rates. Based on the data from a
      previously reported, prospective multicenter study encompassing eight dialysis
      centers in Japan (Am J Kidney Dis 2002; 40:1045-54), we recalculated patient and
      technique survival data. We reviewed the records of 139 patients newly initiated
      on CAPD from January 1995 to December 1999. Peritoneal permeability was estimated
      by PDC test within the first year after initiation. We divided the patients into
      paired groups according to several peritoneal permeability variables as
      calculated by the PDC test (area, plasma loss, and peritoneal creatinine
      clearance), and we compared patient and technique survival rate between the
      groups. The mean age of the patients was 49.6 years +/- 14.9 years (standard
      deviation). The mean pore area of peritoneum was 19,936 +/- 8383 cm/1.73 m2.
      Estimation of patient survival by the Kaplan-Meier method showed 94.2%, 88.4%,
      84.1%, and 79.7% at 1, 2, 3, and 5 years respectively. Estimated technique
      survival (including death as an endpoint) by the Kaplan-Meier method showed
      90.6%, 76.8%, 67.4%, and 54.3% at 1, 2, 3, and 5 years respectively. In the high
      peritoneal permeability group (high area and high plasma loss), the technique
      survival at 5 years was significantly lower than in the low peritoneal
      permeability group [area: 55.9% (high) vs. 72.7% (low), p = 0.0459; plasma loss:
      43.3% (high) vs. 62.8% (low), p = 0.0197). We observed no significant difference
      in patient survival between the high and low peritoneal permeability patients. In
      the high peritoneal creatinine clearance group, patient and technique survival
      were both significantly lower than in the high peritoneal creatinine clearance
      group. Patients with high peritoneal permeability as calculated by the PDC test
      at the start of PD had a poor prognosis for technique and patient survival on
      CAPD. We conclude that early estimation of high peritoneal permeability can
      predict poor outcome for patients on CAPD.

PMID- 16983932
TI  - The newly developed calcium antagonist, azelnidipine, increases drain volume in
      continuous ambulatory peritoneal dialysis patients.
AB  - Many patients undergoing continuous ambulatory peritoneal dialysis (CAPD) receive
      antihypertensive agents, including calcium antagonists, which produce reflex
      tachycardia through activation of the sympathetic nervous system. Azelnidipine, a
      newly developed calcium antagonist, has unique characteristics in that it causes
      less reflex stimulation of the sympathetic nervous system. In the present study,
      we used a crossover method to compare the effects of amlodipine (5-10 mg daily)
      and azelnidipine (8-16 mg daily) on drain volume and weekly creatinine clearance
      in 9 CAPD patients (3 women, 6 men; mean age: 64 +/- 5 years; mean duration of
      CAPD: 1.8 +/- 0.6 years). Each calcium antagonist was administered for 3 months
      and then switched for the other. As compared with amlodipine, azelnidipine
      increased drain volume by 13% +/- 2% (p < 0.05) and weekly creatinine clearance
      by 12% +/- 2% (p < 0.05). At the same time, we observed no significant
      differences in blood pressure and urine volume. The increases in drain volume
      produced by azelnidipine resulted from less activation of the sympathetic nervous
      system. We therefore suggest that activation of the sympathetic nervous system
      induced by calcium antagonists may be important in the regulation of drain volume
      in CAPD patients.

PMID- 16983933
TI  - Impact on peritoneal membrane of use of icodextrin-based dialysis solution in
      peritoneal dialysis patients.
AB  - The usefulness of icodextrin-containing peritoneal dialysis (PD) solution for the
      management of body fluid and blood pressure has been reported. However,
      icodextrin PD solution is a foreign solution in the body, and the possible
      induction of intraperitoneal inflammation has been reported. In this study, we
      investigated at 6-month intervals the influence of icodextrin solution on
      peritoneal permeability and inflammatory reactions in patients in whom glucose
      solution had been changed to icodextrin solution for the overnight dwell. We
      enrolled 9 anuric PD patients (5 men, 4 women) of mean age 58 +/- 5.9 years
      (range: 45.6-64.8 years) into the study. The patients' mean duration of PD was
      61.9 +/- 42 months (range: 6.7-142.5 months). The cause of end-stage renal
      disease was chronic glomerulonephritis in all patients. For evaluation
      ofperitoneal permeability, we performed peritoneal equilibration tests (PETs)
      immediately after an overnight dwell and determined the dialysate-to-plasma
      ratios of creatinine (D/P Cr), beta2-microglobulin (D/P beta2m), albumin (D/P
      Alb), immunoglobulin G (D/P IgG), and alpha2-macroglobulin (D/P alpha2m). We also
      measured interleukin-6 (IL-6) and fibrinogen degradation products (FDPs) in
      overnight effluent as indices of inflammation and of the fibrinolysis-coagulation
      system. The evaluation was performed every 6 months for 24 months. The FDPs in
      effluent increased significantly at 6 months after the change to icodextrin
      solution, and IL-6 tended to increase. The D/P beta2m, D/P Alb, D/P IgG, and D/P
      alpha2m all significantly increased in the course of follow-up. In the PETs, the
      D/P Cr increased slightly, but the change was nonsignificant. At 30 months after
      the change to icodextrin solution, 1 patient was diagnosed as having a risk of
      encapsulating peritoneal sclerosis (pre-EPS). In this patient, rapid increases in
      IL-6, D/P Cr and macromolecular and small molecular D/P by PET were noted after
      the change to icodextrin solution. Steroids were administered after the diagnosis
      of pre-EPS, with the result that the IL-6 level rapidly decreased and the D/P Cr
      and D/P of small molecules and macromolecules slightly decreased. Icodextrin
      dialysis solution increased peritoneal permeability. Although the cause was
      unclear, icodextrin may have changed peritoneal reactivity. Long-term use of
      icodextrin PD solution requires further investigation.

PMID- 16983934
TI  - Effect of hyaluronan and deoxycholate on transperitoneal insulin and albumin
      transport in vitro.
AB  - In patients with end-stage renal disease on peritoneal dialysis, the peritoneum
      is effectively utilized as an endogenous semipermeable membrane. Chemical agents
      may alter the structure of the peritoneum and induce changes in its transfer
      properties. The purpose of our in vitro study was to compare the influence of
      sodium hyaluronan (a cytoprotective glycosaminoglycan, 2000 kDa, 40 mg/dL) and
      sodium deoxycholate (an intense oxidative stress factor, 414 Da, 104 mg/dL) on
      the transfer of insulin (5.8 kDa, 100 mg/dL) and albumin (68 kDa, 1000 mg/dL)
      through isolated rabbit parietal peritoneum. We used a mathematical model to
      calculate the transport rate of solutes from the interstitial to the mesothelial
      side of peritoneal membrane (I-->M) and in the opposite direction (M-->I) in
      three separate series of experiments: Control conditions without chemical agents
      Before (15-60 minutes) and after (75-120 minutes) introduction of sodium
      hyaluronan into the experimental system Before (15 -75 minutes) and after (90-150
      minutes) introduction of sodium deoxycholate into the experimental system The
      results are expressed as a diffusive permeability coefficient P in centimeters
      per second. During the 120 minutes of the control stage, the rate of insulin and
      albumin bidirectional passage remained constant. Values of P +/- standard error
      of the mean did not correlate with the molecular weight of the compounds and
      measured 0.145 +/- 0.033 x 0.0001 cm/s and 0.146 +/- 0.022 x 0.0001 cm/s for
      insulin, and 0.271 +/- 0.056 x 0.0001 cm/s and 0.315 +/- 0.057 x 0.0001 cm/s for
      albumin in the I-->M and M-->I transport directions respectively. Application of
      sodium hyaluronan did not change the bidirectional transport of either solute.
      However sodium deoxycholate caused the values of P to increase by 142% (p < 0.05)
      for insulin I-->M transfer and by 102% (p < 0.02) for insulin M-->I transport.
      Albumin passage increased by 193% (p < 0.01) for both transfer directions. We
      conclude that, in vitro, sodium deoxycholate but not sodium hyaluronan increases
      the bidirectional peritoneal transport of insulin and albumin. In the case of
      larger molecular weight solutes, the modification is greater.

PMID- 16983935
TI  - Peritoneal transport in peritoneal dialysis patients is not affected by
      transitorily successful renal transplantation.
AB  - Patients returning to peritoneal dialysis (PD) from failed renal transplantation
      are recognized to be inflamed, and this situation might produce a high peritoneal
      solute transport status. We wanted to determine if a period of time with a kidney
      allograft induces a change in peritoneal function. We studied 19 PD patients who
      had been living with a graft for a mean of 47 +/- 39 months. We studied their
      peritoneal function upon starting PD (baseline), immediately before
      transplantation (pre-Tx), and after returning to PD when the graft failed (post
      Tx). We analyzed the peritoneal mass transfer coefficients for urea (U-MTAC) and
      creatinine (Cr-MTAC), the dialysate-to-plasma ratio of creatinine (D/P-Cr), and
      net ultrafiltration (UF). We observed no significant differences in the various
      variables pre-Tx and post-Tx. The U-MTAC post-Tx was significantly lower than at
      PD baseline (25.9 +/- 8 mL/min vs. 20.2 +/- 5 mL/min, p = 0.03). The U-MTAC and
      Cr-MTAC post-Tx were not correlated with months on a graft or with MTAC values at
      baseline. In inherent high transporters (Cr-MTAC > or = 11.5 mL/min at baseline,
      n = 8), we observed a significant reduction in Cr-MTAC post-Tx (15.2 +/- 2 mL/min
      vs. 10.2 +/- 4 mL/min, p = 0.03). Three of these patients remained high
      transporters post-Tx. We conclude that peritoneal function upon reinitiating PD
      after transplantation is similar to function in the pre-transplantation phase;
      and that a high peritoneal transport status is more prevalent at first initiation
      onto PD than at return after transplantation, suggesting that inherently high
      transport is almost exclusively a feature of an intact, predialysis peritoneum.

PMID- 16983936
TI  - Expression of vascular endothelial growth factor, fibroblast growth factor, and
      lactate dehydrogenase by human peritoneal mesothelial cells in solutions with
      lactate or bicarbonate or both.
AB  - In patients on long-term continuous ambulatory peritoneal dialysis, the
      efficiency of dialysis declines because of peritoneal neovascularization and loss
      of peritoneal mesothelial cells. In this study, we investigated the influence of
      lactate and bicarbonate in peritoneal dialysis fluid on such changes of the
      peritoneum. We studied the production of vascular endothelial growth factor
      (VEGF) and basic fibroblast growth factor (bFGF), which induce peritoneal
      neovascularization, by human peritoneal mesothelial cells (HPMCs) cultured with
      lactate or bicarbonate or both. Lactate dehydrogenase (LDH) was also measured to
      assess cell necrosis. Levels of VEGF, bFGF, and LDH in the culture supernatant
      showed a significant decrease after incubation of HPMCs with 15 mEq/L lactate
      plus 25 mEq/L bicarbonate, or with 40 mEq/L bicarbonate, as compared with
      incubation with 40 mEq/L lactate. Levels of VEGF and bFGF showed a concentration
      dependent decrease when the cells were incubated with lactate or bicarbonate; a
      concentration-dependent increase of LDH was simultaneously observed. These
      results suggest that dialysis fluid containing 40 mEq/L bicarbonate is superior
      to fluid containing 40 mEq/L lactate with regard to its influence on the
      production of VEGF and bFGF although lactate and bicarbonate are both toxic for
      HPMCs.

PMID- 16983937
TI  - In patients treated with peritoneal dialysis, icodextrin improves erythropoietin
      resistant anemia through blockade of asialo receptors on hepatocytes.
AB  - Although erythropoietin (EPO) derivatives improve anemic status in most end-stage
      renal disease patients, some EPO-resistant patients remain. Asialo-type EPO is as
      effective as is native EPO in vitro, but in vivo, it is quickly trapped by the
      hepatic asialo receptors. Alkaline phosphatase (ALP) also binds to the asialo
      receptor for degradation. We compared hematologic indices in 27 stable PD
      patients 1-3 months before and after the start of icodextrin solution. In
      selected patients, we also performed imaging with 99m-technetium-labeled
      galactosyl serum albumin (GSA) for asialo receptors. Resistance to EPO was
      defined as a hematocrit below 30% concurrent with EPO administration of more than
      18,000 IU monthly. In 19 patients without EPO resistance started on icodextrin,
      the average hematocrit level did not change (-1.2%), and the average ALP activity
      increased 36%. But in 8 patients with EPO resistance, the average hematocrit
      level increased by 12% (p = 0.03 as compared with baseline), and ALP activity
      increased by 79% (p = 0.02 as compared to non EPO resistant cases) after
      icodextrin introduction. In the patients with marked elevation of ALP activity,
      GSA scintigraphy showed inhibition of tracer binding. These results indicate that
      improvement in EPO-resistant anemia and greater ALP activity with icodextrin
      administration are mediated through blockade of the asialo receptors on
      hepatocytes.

PMID- 16983938
TI  - Outcome of patients who develop early-onset peritonitis.
AB  - Although advances have been made in the treatment and prevention of peritoneal
      dialysis (PD) peritonitis, these infections are still a significant source of
      technique failure, morbidity, and mortality in the end-stage renal disease
      population. Currently, it is unclear whether PD patients who experience an
      episode of peritonitis early in the course of their therapy are more vulnerable
      to the complications of peritonitis. Using retrospective data collected at the
      Toronto General Hospital Home Peritoneal Dialysis Unit between January 1, 1998,
      and December 31, 2004, we compared technique and patient outcomes between PD
      patients developing "early-onset" peritonitis and a matched control group of PD
      patients. "Early-onset" peritonitis was defined as peritonitis occurring within 3
      months of PD catheter insertion. Outcomes included survival on PD or the combined
      endpoint of technique failure (transfer to hemodialysis) or death. The early
      onset cohort was younger than the control group and had a higher peritonitis rate
      (1.18 episodes vs. 0.28 episodes per patient-year). Gram-positive micro
      organisms, particularly coagulase-negative staphylococci, were the most common
      cause of peritonitis. At the conclusion of the study, 8 patients (38.1%) in the
      early-onset cohort had transferred to hemodialysis, 2 patients (9.5%) had died of
      cardiac complications, and 11 patients (52.4%) remained on PD. The combined rate
      of technique failure and death in the early-onset group was almost twice as high
      as that in the control group (0.282 vs. 0.175 per patient-year). Time to the
      composite end-point of technique failure or death did not significantly differ
      between the two groups (p = 0.26). In summary, there is an important trend toward
      increased death and technique failure in PD patients who develop peritonitis
      early in the course of their PD therapy.

PMID- 16983939
TI  - Peritonitis during the first year after commencement of peritoneal dialysis has
      an impact on technique survival and patient morbidity.
AB  - The timing of the first episode of peritonitis in peritoneal dialysis (PD) might
      have some special characteristics and may depend on many factors such as a
      patient's attitudes, age, comorbidity, or training capacity. It may also have a
      significant impact on further peritonitis episodes and technique failure. We
      retrospectively analyzed data for 168 PD patients who were undergoing continuous
      ambulatory PD by a twin-bag system, automated PD, or in-center intermittent PD
      over 12 years. There were 121 cases of peritonitis recorded in 60 patients, with
      an overall peritonitis rate of 1 episode per 45.75 patient-months. The mean time
      to the first episode of peritonitis after commencement of PD was 26.4 +/- 22
      months (range: 1-110 months). In 20 patients, a first peritonitis episode
      presented rather early--during the first 12 months on PD (group A)--and in 27
      patients, a first episode presented rather late-after at least 24 months on PD
      (group B). Group A had lower technique survival (30.4 +/- 26.5 months), were more
      prone to further episodes of peritonitis during follow-up, and had a total
      peritonitis rate of 1 episode per 14.85 patient-months. In group B, technique
      survival was longer (69.3 +/- 33.8 months), and the total peritonitis rate was 1
      episode per 45.68 patient-months. We observed no differences between the two
      groups in comorbidity, age, or PD modality. These results indicate that patients
      with early-onset peritonitis are prone to making mistakes during connection,
      resulting usually in infection with gram-positive pathogens. These patients may
      present repeated peritonitis episodes and experience decreased technique
      survival.

PMID- 16983940
TI  - Fungal peritonitis complicating peritoneal dialysis: report of 18 cases and
      analysis of outcomes.
AB  - Fungal peritonitis is a significant cause of morbidity and mortality in patients
      undergoing peritoneal dialysis (PD). This retrospective study evaluated patients
      with fungal peritonitis in our dialysis unit from December 1999 through September
      2003. We analyzed the demographic and clinical characteristics of patients to
      identify possible risk factors. Main clinical outcomes of interest were technique
      survival and mortality. During the study period, 18 patients were diagnosed with
      fungal peritonitis (15 on continuous ambulatory PD, 3 on automated PD). Fungal
      peritonitis accounted for 6% of all peritonitis episodes during the study period.
      Candida species were the infecting organism in 15 patients (83%). All 18 patients
      received antifungal treatment according to the International Society of
      Peritoneal Dialysis (ISPD) recommendations that were current during the study
      period. Two patients (11%) died with the PD catheter in situ, and 1 patient died
      after dialysis was withdrawn because of deterioration in other comorbid
      conditions. All the surviving patients were switched to hemodialysis. Of the 18
      patients, 15 (83%) had history of antibiotic treatment for bacterial peritonitis
      within the 4 weeks preceding the fungal peritonitis episode. Our study provides
      further support for the current ISPD recommendation that the PD catheter should
      be removed as soon as a diagnosis of fungal peritonitis is made in a patient.

PMID- 16983941
TI  - Experience of 100 surgical cases of encapsulating peritoneal sclerosis:
      investigation of recurrent cases after surgery.
AB  - Since 1993, we have performed enterolysis for encapsulating peritoneal sclerosis
      (EPS) in 86 patients. Five patients died after surgery, but the remaining 81
      patients achieved symptomatic improvement. However, some of the surviving
      patients developed symptoms of intestinal obstruction after several months, and
      EPS recurrence remains our greatest challenge. In the present study, we
      identified factors related to recurrence by clinically comparing 47 recurrent and
      nonrecurrent patients that we were able to follow for more than 2 years after
      surgery. In the 47 patients we followed, 11 (23.4%) experienced recurrence, and
      10 of those patients underwent a second surgery. Four patients needed a third
      surgery. The mean time to recurrence was 15.2 months, and all patients with
      recurrence, except one, experienced their recurrence within 20 months. We
      observed no differences between the recurrent and nonrecurrent patients in follow
      up period, age, history of peritoneal dialysis, use or nonuse of steroids after
      surgery, thickness of the submesothelial compact zone, or inflammatory cell
      infiltration. However, the number of microvessels was significantly higher in the
      recurrent patients. Our surgical experience with EPS shows recurrence in
      approximately 23% of patients. The results of the present study suggest that
      peritoneal microvascular hyperplasia is a factor involved in recurrence, and that
      patients with recurrence may have an irreversible pathologic condition and may
      experience repeated recurrences.

PMID- 16983942
TI  - Efficacy and safety of meropenem plus tobramycin followed by meropenem plus
      vancomycin for treating peritonitis in patients on continuous ambulatory
      peritoneal dialysis.
AB  - Peritonitis is a serious complication in patients on peritoneal dialysis. We
      examined the efficacy of MTV therapy [first 7 days: meropenem 0.5 g intravenously
      (IV) twice daily, plus tobramycin 15 mg intraperitoneally (IP) in every dialysis
      bag; next 7 days: meropenem 0.5 g IV twice daily, plus vancomycin 8 mg/kg IP in
      every bag after a 1-g loading dose] on peritonitis in patients undergoing
      continuous ambulatory peritoneal dialysis (CAPD), comparing it with the treatment
      previously recommended by the International Society for Peritoneal Dialysis
      (combination of first-generation cephalosporins and aminoglycosides). We treated
      36 CAPD peritonitis episodes with MTV therapy. Outcome measures were primary
      response rate at day 14 and relapse rate within 28 days after the start of
      antibiotic therapy. The primary response rate was 34/36 (94.4%). No patients
      treated with MTV therapy required catheter removal. We observed no serious side
      effects in these patients. We conclude that MTV therapy may be an even better
      choice of treatment for peritonitis in patients on CAPD than was the previous
      empirical treatment (combination of first-generation cephalosporin and
      aminoglycosides).

PMID- 16983943
TI  - Hypotonia during amikacin administration in a patient treated with continuous
      ambulatory peritoneal dialysis.
AB  - In this report we present the history of a patient treated with continuous
      ambulatory peritoneal dialysis (CAPD) in whom episodes of hypotonia can be
      related to the administration of amikacin, an antibiotic from the aminoglycosides
      group. The 68-year-old female patient was admitted for initiation of renal
      replacement therapy with CAPD. Her renal failure was probably attributable to
      hypertension. Three days after catheter implantation, the patient reported
      dysuric symptoms, and a urine culture showed significant growth of Escherichia
      coli. Amikacin 250 mg and cefazolin 1.0 g were administered intravenously once
      daily in accordance with the antibiogram. On the third day of antibiotic
      administration, the patient fainted, showing an arterial blood pressure of 90/60
      mmHg. On the subsequent 2 days, decreases of postural arterial blood pressure to
      between 90/60 mmHg and 80/50 mmHg were reported two or three times daily. The
      patient was treated with antibiotics for the next 6 days and felt very bad the
      entire time, with an arterial blood pressure of 80/50 mmHg. The patient's
      condition improved 2 days after discontinuation of treatment with antibiotics,
      and episodes of hypotonia stopped. The decrease in the arterial blood pressure
      observed in our patient during intravenous administration of amikacin can, with a
      high probability, be related to the calcimimetic activity of this aminoglycoside
      and the resulting inhibition of parathyroid secretion.

PMID- 16983944
TI  - Technique survival with Serratia peritonitis.
AB  - Despite a decreasing incidence, peritonitis remains an important cause of
      peritoneal dialysis (PD) technique failure and transfer to hemodialysis.
      Infection with Serratia spp. has been suggested to be associated with a poor
      technique outcome in PD. We examined the data at our center to see if patients
      with Serratia peritonitis had a similar poor outcome. In this retrospective
      study, we reviewed all PD patients who presented at our center with peritonitis
      from January 1996 to December 2003. The case records of patients in whom the
      infecting organism was identified as Serratia were evaluated. We recorded age at
      the time of peritonitis and at the start of PD, sex, presence of diabetes
      mellitus, PD modality at the time of peritonitis, and duration of PD before the
      onset of peritonitis. For each episode of peritonitis, we recorded the type and
      duration of antibiotic therapy and the outcome. Over the study period, 52% of all
      peritonitis episodes involved gram-positive organisms; 29%, gram-negative
      organisms; and 19%, other organisms. Serratia spp. accounted for 16 episodes
      (3.68%). These 16 episodes of peritonitis occurred in 12 patients, with 3 repeat
      infections and 1 relapsing infection. The distribution between the sexes was
      equal, and the median age at diagnosis was 67 years (range: 37-79 years). Four
      patients with diabetes accounted for 6 of the 16 episodes (37.5%). In 7 episodes
      (43.8%), a Serratia exit-site infection preceded the peritonitis. In 4 episodes,
      catheter removal was required. A fifth patient developed sepsis and died.
      Technique survival was therefore 68.8% (11 of 16 episodes). We also compared the
      outcomes of different initial antibiotic regimens. With an initial regimen based
      on cefazolin-ceftazidime, as suggested in the 2000 guidelines of the
      International Society for Peritoneal Dialysis, technique survival was 60% (3 of 5
      episodes). When the initial regimen included an aminoglycoside, the technique
      survival was 80% (8 of 10 episodes). Serratia-induced peritonitis was associated
      with a technique survival of 68.8% at our center.

PMID- 16983945
TI  - Risk of technique failure and death in fungal peritonitis is determined mainly by
      duration on peritoneal dialysis: single-center experience of 24 years.
AB  - Fungal peritonitis (FP) is an infrequent cause of peritonitis in peritoneal
      dialysis (PD), but it has high morbidity and mortality. We analyzed the
      experience with FP in a single PD unit over a 24-year period. We identified 671
      episodes of peritonitis that occurred in 496 patients during the study period. Of
      these episodes, 23 (3.4%) were FP episodes occurring in 21 patients. In the FP
      episodes, the patients' mean time on PD was 29.2 +/- 27 months. In 5 episodes,
      the patients had experienced a peritonitis episode within the preceding month,
      and in 11 episodes, the patients had used antibiotics within the preceding month.
      The FP diagnosis was made a mean of 3.17 +/- 3 days after the diagnosis of
      peritonitis, and in 1 patient, the diagnosis was made after death. Candida spp.
      were isolated in 82.6% of patients. In 91.3%, the peritoneal catheter was
      removed. After the FP diagnosis, 15 patients dropped out of PD, but in only 8
      patients (34.7%) was drop-out related to FP. In 4 patients, drop-out occurred
      because of peritoneal membrane failure, and 4 patients (17.4%) died. Time on PD
      was significantly higher in the group of patients that dropped out of PD because
      of the FP (45.7 +/- 31 months vs. 19 +/- 18 months, p = 0.02). Fungal peritonitis
      is a rare cause of peritonitis in PD patients, but it is associated with high
      morbidity and mortality. Longer time on PD is the main factor in technique
      failure and mortality.

PMID- 16983946
TI  - The relationship between symptoms, depression, and quality of life in peritoneal
      dialysis patients.
AB  - Measurement of patient outcome by mental and social indexes such as quality of
      life (QOL) in addition to survival is a growing trend. We examined the
      feasibility of using a single global QOL question in peritoneal dialysis (PD)
      patients. We also examined the relationship that QOL has with uremic symptoms and
      depression in these patients. During a clinic visit, each PD patient completed a
      single-question QOL measure (0-10 scale, 10 being best). Patients' symptoms were
      assessed using a 10-symptom checklist, with each symptom scored on a Likert scale
      of 0 (none) to 5 (severe). We evaluated for depression using two questions from
      the Primary Care Evaluation of Mental Disorders. Serum albumin, hemoglobin, and
      phosphorus were obtained, but only phosphorus was associated with QOL on
      univariate analysis (p = 0.05) and therefore included in the multivariate model.
      Results (checklist score, depression, phosphorus, age, diabetes, and race) were
      analyzed using a sequential multivariate analysis with QOL as the dependent
      variable. The study population consisted of 64 PD patients [mean age: 47 +/- 16
      years; 25% black; 23% with diabetes; 31% incident (< or =3 months)]. The median
      score on the single QOL question was 7 (range: 1-10). Patients scored a median of
      9 (range: 0-31) out of 50 on the total symptom checklist. Among responding
      patients, 34% answered yes to at least one depression question. The sequential
      incremental r2 values associated with a poorer QOL were higher checklist score
      (r2 = 0.16, p < 0.02), presence of depression (r2 = 0.13, p < 0.00002), younger
      age (r2 = 0.06, p < 0.03), and presence of diabetes (r2 = 0.04, p < 0.05). In
      this model, PO4 and race were nonsignificant. Total r2 in the model was 0.48. The
      single measure of QOL, the checklist score, and the depression screening score
      were simple and easy to obtain during a routine clinic visit. We conclude that
      physical symptoms and depression are strongly associated with a simple single
      measure of QOL. The extent to which symptoms and depression can be improved by
      clinical intervention, and the subsequent effect on quality of life and survival,
      should be examined in longitudinal studies.

PMID- 16983947
TI  - Effects of glutathione supplementation during peritoneal dialysis.
AB  - We examined the effect of L-2-oxothiazolidine-4-carboxylate (OTZ) on peritoneal
      morphology and function of mesothelial cells in rats during peritoneal dialysis
      (PD). We implanted intraperitoneal catheters into 14 rats and injected the rats
      twice daily for 4 weeks with standard PD fluid (group C, control; n = 7) or PD
      fluid supplemented with OTZ 1 mmol/L (group OTZ; n = 7). At the beginning and the
      end of the study, we collected samples of 4-hour dwell effluents from every rat
      under sterile conditions. We used those samples to test, in ex vivo conditions,
      the effect on primary cultures of rat peritoneal mesothelial cells with regard to
      synthesis of total protein and collagen in mesothelium. After 4 weeks, the rats
      were humanely killed, and glutathione peroxidase activity in erythrocytes was
      measured. Morphologic analysis of the peritoneal membrane was also performed. As
      compared with group OTZ, group C showed intraperitoneal adhesions that were more
      severe, a higher density of mesothelial cells, a higher density of peritoneal
      vessels, similar peritoneal thickness, lower activity of glutathione peroxidase,
      and greater ability of their dialysate effluent to induce synthesis of total
      proteins and collagen in cultured mesothelial cells. Relationships between
      various parameters were analyzed. We conclude that OTZ preserves peritoneal
      morphology and the function of mesothelial cells during PD.

PMID- 16983948
TI  - Clinical outcome after transfer from peritoneal dialysis to hemodialysis.
AB  - Guidelines for the clinical care and management of intra-abdominal complications
      in patients transferred from peritoneal dialysis (PD) to hemodialysis (HD) are
      not well established. In this study, we analyzed the indications for transfer,
      presence of abdominal complications, and clinical outcome on HD of 26 patients
      who were followed up between 1996 and 2004. Laboratory and radiology data for the
      patients (computerized tomographic and ultrasonographic examinations performed
      during the transfer and annually thereafter) were collected retrospectively. The
      indications for transfer from PD to HD were peritonitis (19%), mechanical
      problems (39%), and ultrafiltration failure (42%). At the time of transfer, 11
      patients had no intra-abdominal complications, 8 had intra-abdominal loculated
      fluid collection, and 7 had intra-abdominal free fluid. One year after transfer,
      intra-abdominal fluid collection was observed in 6 patients, 3 of whom received
      percutaneous drainage. Patients who had intra-abdominal complications at the time
      of transfer exhibited significantly lower albumin (p < 0.01), higher levels of C
      reactive protein (p < 0.02), and erythropoietin resistance at the time of
      transfer (p < 0.0001). During the first year after transfer, we observed a
      tendency toward an increase in albumin and a decrease in C-reactive protein level
      in the group that had complications, and yet nutritional interventions were still
      necessary in that group. A high ratio of intra-abdominal problems, which have
      adverse nutritional and inflammatory impacts, are seen after patients are
      transferred from peritoneal dialysis.

PMID- 16983949
TI  - Intravenous iron does not affect the rate of decline of residual renal function
      in patients on peritoneal dialysis.
AB  - The preservation residual renal function (RRF) is important for adequacy of
      peritoneal dialysis. Oxidative stress from intravenous (IV) iron has been shown
      to cause renal damage. The effect of IV iron on RRF has not been studied. Here,
      we report our experience during April 1999-March 2005 of the effect of IV iron on
      RRF. The study group included 24 patients (9 men, 15 women). The mean age of the
      group was 61 +/- 17.7 years. Diabetes mellitus and hypertension were the
      underlying cause of end-stage renal disease in 55% of the patients. We found
      serum creatinine, creatinine clearance, urea clearance, urine output, hemoglobin,
      transferrin saturation, and ferritin all to be statistically significantly
      different before and after administration of IV iron to the patients. However,
      the rate at which the glomerular filtration rate (GFR) declined over time did not
      change significantly when calculated for the period before and after the iron
      infusion, suggesting that the changes we observed after IV iron infusion were the
      result of the declining RRF--the rate of that decline being unaffected by the IV
      iron. Furthermore, the rate of GFR decline in this study was similar to that
      previously reported in our patients.

PMID- 16983950
TI  - Gross calcification of the small bowel in a continuous ambulatory peritoneal
      dialysis patient with sclerosing peritonitis.
AB  - We present here the case of a continuous ambulatory peritoneal dialysis (CAPD)
      patient who developed sclerosing calcifying peritonitis with gross macroscopic
      calcification of the small bowel, a rare and life-threatening complication of
      sclerosing peritonitis. A 40-year-old female had been on CAPD for 7 years. A
      peritoneal biopsy during an open cholecystectomy for cholelithiasis showed
      sclerosing peritonitis, but the patient refused to change dialysis modality. She
      remained free of symptoms for 3 years, but then was admitted with cloudy
      effluent, abdominal pain, and referred pain to the left shoulder. A white blood
      cell count showed 25,000 cells/microL, and a peritoneal cell count showed 1000
      cells/microL. An abdominal computed tomography scan was nondiagnostic. The
      patient was started on intraperitoneal antibiotics, but 3 days later she was
      taken for surgery because of acute abdomen. Laparotomy revealed a tanned and
      thickened peritoneum and a small bowel with significant fibrosis and foci of
      calcification on the antimesenteric surface. Enterectomy and primary anastomosis
      was performed. Pathology revealed extensive mural fibrosis, calcium deposition,
      and localized inflammatory infiltration of the small bowel. The patient developed
      an anastomotic leak and, despite a second operation, died in the intensive care
      unit from septic shock. Although some authors report successful outcomes in
      similar cases by using surgery or other treatments (parenteral nutrition,
      immunosuppression), or both, we urgently recommend that, if sclerosing calcifying
      peritonitis is diagnosed, the patient be switched promptly to hemodialysis.

PMID- 16983951
TI  - Icodextrin reduces mortality and the drop-out rate in Japanese peritoneal
      dialysis patients.
AB  - Although numerous reports have shown that the use of icodextrin solution, as
      compared with conventional dextrose solutions, provides various clinical
      benefits, data on the impact of icodextrin solution on mortality and drop-out are
      sparse. In the present retrospective study, we compared clinical outcomes in a
      large cohort of patients prescribed either icodextrin or dextrose solution for
      the long dwell. A total of 7808 patients across Japan who were using Baxter
      peritoneal dialysis (PD) solutions in 2004 were included in this cross-sectional
      analysis. Outcomes data were retrieved from the Baxter Japan database. The annual
      drop-out rate in the icodextrin group (8.9%) was significantly (p < 0.0001) lower
      than that in the dextrose group (14.5%). The annual mortality rate was also lower
      (6.6% vs. 13.5%, p < 0.0001). Using data from the 2000 report of the Japanese
      Society for Dialysis Therapy, the relative risk of death in the icodextrin group,
      regardless of PD duration, was consistently lower than that in hemodialysis
      patients. These results indicate that, in PD, the use of icodextrin solution (as
      compared with dextrose solution) significantly reduces both mortality and drop
      out rate.

PMID- 16983952
TI  - Cardiovascular issues in dialysis patients: challenges and newer insights.
AB  - Cardiovascular disease is the leading cause of death among people with chronic
      kidney disease. In this review, we provide an update on how the association
      between renal dysfunction and cardiovascular disease goes beyond traditional
      cardiac risk factors, and we consider some of the key studies that link renal
      dysfunction with the development of cardiovascular morbidity and mortality.
      Unique challenges facing clinicians that treat patients with end-stage renal
      disease, particularly patients on peritoneal dialysis, are discussed. The
      potential relationship between endothelial progenitor cells and the renal
      cardiovascular relationship are explored. We propose that moderate-to-severe
      renal dysfunction should be considered a coronary artery disease equivalent and
      that further investigation needs to be conducted to understand this key
      relationship.

PMID- 16983953
TI  - Patients with learning difficulties: outcome on peritoneal dialysis.
AB  - In the present study, we identified patients who had difficulties learning the
      minimum knowledge and skills required to carry out peritoneal dialysis (PD), and
      we compared the outcomes in this subgroup of patients with outcomes in the
      general PD population. We calculated the mean learning sessions needed by our
      total PD population during the training period. We then assigned patients to one
      of two groups according to the number of learning sessions they needed. Patients
      who required a number of sessions equal to or less than the mean were placed in
      the "standard learning" group; patients who required more sessions but who
      reached the minimum knowledge and skills were placed in the "learning
      difficulties " group. We compared these two groups in terms of age, sex, diabetes
      status, autonomy to perform PD, family support, education level, residual renal
      function, and Charlson comorbidity index. Outcomes on PD included time to first
      peritonitis episode, peritonitis rate, percentage of patients free of peritonitis
      during follow-up, survival time on PD, and transfer to hemodialysis. Patients
      with learning difficulties were older and had more comorbidities. Outcomes on PD
      in the learning difficulties group were similar to those in the standard learning
      group, except for time to first peritonitis.

PMID- 16983954
TI  - Perioperative management of peritoneal dialysis patients: review of abdominal
      surgery.
AB  - On abdominal computed tomography scan for evaluation of hematuria, the index
      patient, a 23-year-old male, was found to have multiple renal cysts bilaterally.
      He had been on peritoneal dialysis for 6 years, complicated by intermittent
      episodes of exit-site infection and peritonitis. Over time, he developed
      recurrent urinary tract infection and nephrolithiasis with intermittent
      hematuria. His maintenance dose of recombinant erythropoietin was discontinued,
      and he maintained a normal hemoglobin level. Annual surveillance of the bilateral
      renal cysts with magnetic resonance imaging revealed development of a complex
      cystic mass that warranted further investigation. Following a urology
      consultation, laparoscopic nephrectomy was performed without complications and
      with minimal interruption of PD. Pathology evaluation revealed renal cell
      carcinoma within the renal parenchyma and multiple cystic structures consistent
      with acquired cystic kidney disease. No clear recommendations exist in the
      literature regarding continuation or interruption of PD in the perioperative
      period for planned nephrectomy, tumor resection, or other uncomplicated abdominal
      or retroperitoneal procedures. A perioperative management strategy for PD
      patients requiring abdominal or retroperitoneal surgery is outlined here. If
      these recommendations are followed, patients may continue PD with minimal
      interruption, preservation of the peritoneal membrane, and few complications.

PMID- 16983955
TI  - Disaster planning for peritoneal dialysis programs.
AB  - Because of increased intensity of hurricanes in the Gulf Coast region of the
      United States, peritoneal dialysis (PD) programs have been disrupted and patients
      relocated temporarily following these catastrophic events. We describe the
      disaster planning, implementation, and follow-up that occurred in one such PD
      program in New Orleans following Hurricane Katrina. Each year at the beginning of
      the North American hurricane season, the PD program's disaster plan is reviewed
      by clinic staff and copies are distributed to patients. Patients are instructed
      to assemble a disaster kit and are provided with contact numbers for dialysis
      suppliers and for a PD program in their planned evacuation city. In July 2005,
      this disaster plan was tested when an early tropical storm and hurricane entered
      the Gulf and several patients briefly relocated or evacuated because of power
      loss and then returned without incident. However, when Hurricane Katrina, a
      category 5 storm, was predicted to strike the metropolitan area, patients were
      notified by telephone to evacuate, and contact information, including their
      evacuation city and telephone and cellular phone numbers, was obtained. Patients
      were also reminded to take all medications, bottled water, antibacterial soap,
      hand sanitizer, and 4-5 days of PD supplies. Following the storm, telephone and
      cellular phone services were severely disrupted. However, text messaging was
      available to contact patients to confirm safety and to provide further
      instructions. Arrangements with the major dialysis suppliers to ship emergency
      supplies to new locations were made by the PD nurse and the patients. Only 2 of
      22 patients required hospitalization because of complications resulting from
      evacuation failure, contamination, and inability to perform dialysis for a
      prolonged period of time. Both of these patients were quickly released and have
      continued PD. Following the event, all patients remained on PD, and most have
      planned to return to their home PD program. Thorough preparation, planning,
      practice, and implementation and effective communication are necessary to prevent
      complications in PD patients who are affected by disasters. With advdnce
      preparation, maintenance of communication with health care providers, and
      planning for alternative sites of care, patients can be safely maintained on PD
      without complications following catastrophic natural disasters.

PMID- 16983956
TI  - Total carnitine and acylated carnitine ratio: relationship of free carnitine with
      lipid parameters in pediatric dialysis patients.
AB  - Carnitine has an essential role in the mitochondrial oxidation of long-chain
      fatty acids. Carnitine deficiency has been described in patients with chronic
      kidney disease. Total carnitine (TC) deficiency or a lower-than-normal ratio of
      free carnitine to acylated carnitine (FC:AC) has been shown to be associated with
      disorders in metabolism and plasma lipids. Metabolism and therapeutic use of
      carnitine have therefore been a major area of interest in dialysis patients. In a
      prospective observational study, we determined carnitine status (TC and FC:AC)
      and its correlations with lipid plasma levels in peritoneal dialysis (PD) and
      hemodialysis (HD) patients. In pediatric patients on chronic PD or HD, we
      evaluated nutritional status (weight and height), biochemical parameters (TC, FC,
      and AC levels), and fasting plasma lipoprotein concentrations. We studied 35
      patients (16 boys, 19 girls; 25 on PD, 10 on HD). Median age was 5 years (range:
      3 months-15 years). Median weight-to-height Z-score was -0.5 (range: -2.1 to
      1.9), and median height-to-age Z-score was -2.5 (range: -0.3 to -2.9). The mean
      TC was 65.4 +/- 23.8 pg/mL (normal value: 40-55 pg/mL); the median AC was 18
      pg/mL (range: 2-56pg/mL; normal value: 3-15 pg/mL); and the mean FC was 41.8 +/-
      16.6 pg/mL (normal value: 25-35 pg/mL). Median serum FC:AC was 2.22 (range: 0.59
      4.3; normal value: 4). A significantly higher AC and a lower FC:AC were observed
      in HD patients as compared with PD patients. No differences in TC and FC were
      observed when patients were grouped by dialysis modality, time on dialysis, or
      nutrition status. Total cholesterol was 200 mg/dL or higher in 20 patients, and
      25 patients showed elevated triglycerides (> 150 mg/dL). The latter patients had
      a higher AC than did the group of patients with triglycerides below 150 mg/dL
      (AC: 22 pg/mL and 12.5 pg/mL respectively; Kruskal-Wallis p < 0.003). We found TC
      levels to be high in this group of patients. However, the FC:AC ratio was lower
      than normal in all except in 1 patient. Elevated triglycerides were associated
      with elevated AC, suggesting carnitine insufficiency in our patients.

PMID- 16983957
TI  - Long-term follow-up of patients treated with a combination of continuous
      ambulatory peritoneal dialysis and hemodialysis.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) both have
      advantages in the treatment of patients with renal failure. In CAPD, solute
      removal is sometimes insufficient in patients who have a relatively large muscle
      mass that produces high levels of creatinine. To compensate for this deficiency,
      frequent exchanges and large dialysate volumes are required. We previously
      reported that once-weekly HD helps CAPD patients who experience insufficient
      solute removal. In the present study, we followed, for more than 3 years, 9 CAPD
      patients who underwent additional weekly HD. Add-on HD therapy significantly
      increased the subjects' weekly peritoneal creatinine clearance to 45 +/- 3 L
      (mean +/- standard deviation); these values rose to more than 60 L over the
      course of the study. Our findings suggest that the combined use of CAPD and HD
      improves solute clearance in CAPD patients who are insufficiently dialyzed.

PMID- 16983958
TI  - Continuous ambulatory peritoneal dialysis is effective for patients with severe
      congestive heart failure.
AB  - Although the use of continuous ambulatory peritoneal dialysis (CAPD) to treat
      refractory heart failure is not new, in combination with current medical
      treatment it improves patients'symptoms as well as their cardiac function. We
      started 16 patients (13 men with a mean age of 66.3 +/- 2.8 years, and 3 women
      with a mean age of 72 +/- 4.2 years) on CAPD. All patients were symptomatic with
      congestive heart failure. Mean left ventricular ejection fraction (LVEF) before
      the start of CAPD was 31% +/- 3%. Introduction to CAPD was associated with a
      significant improvement in LVEF (to 44% +/- 6%, p < 0.05) and in blood pressure
      control at 1 year. Also at 1 year, 87% of patients were classified as New York
      Heart Association grade I or II (maximum possible grade is grade III). These
      results suggest that CAPD is a treatment of choice for patients suffering from a
      combination of congestive heart failure and chronic renal insufficiency.

PMID- 16983959
TI  - Current trends in the use of peritoneal dialysis catheters.
AB  - The Tenckhoff catheter was developed in 1968 and has been widely used since for
      chronic peritoneal dialysis (PD) patients. Variations of the Tenckhoff catheter
      have been designed over the years in a search for the ideal PD catheter--an
      access that can provide reliable dialysate flow rates with few complications.
      Currently, data derived from randomized, controlled, multicenter trials dedicated
      to testing how catheter design and placement technique influence long-term
      catheter survival and function are scarce. As a result, no firm guidelines exist
      at the national or international levels on optimal PD catheter type or
      implantation technique. Also, no current statistics on the use of PD catheters
      are available. The last survey was carried out using an audience response system
      at the Annual Peritoneal Dialysis Conference in Orlando, Florida, in January
      1994. The present analysis is based on a new survey done at the 2005 Annual
      Dialysis Conference in Tampa, Florida. It is a snapshot of preferences in
      catheter design and implantation technique in 2004 from an international sample
      of 65 respondent chronic PD centers. The Tenckhoff catheter remains the most
      widely used catheter, followed closely by the swan-neck catheter in both adult
      and pediatric respondent centers. Double-cuff catheters continue to be preferred
      over single-cuff catheters, and coiled intraperitoneal segments are generally
      preferred over straight intra-peritoneal segments. Surgical implantation
      technique remains the prevailing placement method in both pediatric and adult
      respondent centers.

PMID- 16983960
TI  - Transition from gastrostomy to oral feeding following renal transplantation.
AB  - Feeding through a gastrostomy button (GB) provides benefits to the families of
      children on chronic dialysis. But data on the transition to oral feeding
      following renal transplantation--especially in children under 2--is scarce. Here,
      we report our experience of more than 14 years in 22 children who were GB fed at
      under 5 years of age (median age: 1.66 years; range: 0.25-4.25 years). We
      excluded 6 children from the analysis of transition following transplantation
      because of factors precluding early return to oral feeding--specifically,
      cognitive impairment and a tongue tie. We compared 10 children who commenced GB
      feeding at less than 2 years (group 1) with those who commenced at 2-5 years
      (group 2, n = 6). All 16 children made the transition to normal oral feeding by
      10 months post transplantation. Median duration of GB feeding post-transplant in
      group 1 was 0.3 years (range: 0.1-1.0 years) as compared with 0.2 years (range: 0
      0.3 years) in group 2 (p = 0.2). Children with normal cognition and no other
      precluding factors who have a GB inserted at less than 2 years of age can make a
      successful transition from GB to oral feeding with no significant delay. Family
      support should be individualized during this period of potential anxiety.

PMID- 16983961
TI  - Peritoneal dialysis-related hydrothorax--case report.
AB  - Hydrothorax is an uncommon but well-recognized complication of peritoneal
      dialysis. Here, we describe a case of hydrothorax in a peritoneal dialysis
      patient who underwent video-assisted thorascopic surgery and talc pleurodesis for
      a diaphragmatic defect to preserve peritoneal dialysis capabilities. We reviewed
      the literature for 2001-2005 to assess how others have handled this situation and
      whether patients have returned successfully to peritoneal dialysis.

PMID- 16983962
TI  - Why all prescribed medications are not taken: results from a survey of chronic
      dialysis patients.
AB  - Although medication non adherence is common in all populations, including those
      on chronic dialysis, the reasons for medication noncompliance in dialysis
      patients have rarely been examined. We surveyed 54 chronic dialysis patients (15
      on peritoneal dialysis, 39 on hemodialysis), asking about their social and
      financial situations, medication coverage, and reasons for possibly not obtaining
      all prescribed medications. The study population was 56% female, 52% African
      American, 67% over 50 years of age, 27% diabetic, and 61% on dialysis for more
      than 2 years. One patient was unemployed, 33 were retired, 15 were on disability,
      and 5 were employed. A majority (63%) had a household income of dollars 25,000 or
      more annually. Most (70%) had some medication coverage through one or more health
      plans (53% Medicare, 14% Medicaid, 31% private) or a local pharmacy (31% UVA
      pharmacy program for the medically indigent). However, 39% still spent more than
      dollars 100 monthly on medications. Co-pays per prescription ranged from nothing
      (2 patients) to dollars 25 or more (16 patients), with half having a co-pay of
      more than dollars 11 per prescription. Most (69%) took 11 or more medications
      daily. Among all our study patients, 91% reported that they knew their
      medications and the reasons that those medications were prescribed. The choice
      not to fill a prescription was made by 30% of patients either because they had no
      money (67%) or no ride to the pharmacy (17%). When asked if they ever chose not
      to take specific medications, 11 of 53 respondents (21%) said yes because of side
      effects [4 (36%)] or cost [3 (27%)], or because they already take too many
      medications [2 (18%)]. Most respondents (91%) reported discussing their
      medications with their doctors, and a majority (65%) had these discussions at
      least monthly. We conclude that inadequate prescription coverage, lack of
      transportation, and medication cost are primary contributors to medication
      noncompliance among chronic dialysis patients. Patients report knowing their
      medications and the reasons that those medications are prescribed, and having
      ample opportunities to discuss their medications with their physicians. Lack of
      patient education therefore does not seem to be an important factor in medication
      non adherence.

PMID- 16983963
TI  - Clinical use of and experience with neutral-pH solutions.
AB  - New peritoneal dialysis solutions with neutral pH and lactate bicarbonate, or
      combinations of both buffer bases, have been clinically tested in various
      countries. The experience is most encouraging and consistent with the laboratory
      data generated in animals and tissue cultures. The available studies suggest
      improvement in cellular function and viability and better biocompatibility.
      However the reported studies do not define the specific contributions of neutral
      pH per se versus those of bicarbonate or reduction in glucose degradation
      products. Studies designed to address this important question are required.

PMID- 16983965
TI  - Meeting the guidelines for end-of-life care.
AB  - The number of patients initiating dialysis in most countries continues to
      increase, with the greatest increase being in the oldest age group. Clinical
      practice guidelines have been developed to help the nephrology team with end-of
      life carefor patients on dialysis. The aim of the project reported here was to
      assess if we were meeting the guidelines. We conducted a retrospective cohort
      study of all patients 80 years of age and older who had started dialysis at our
      center Our cohort included 105 patients (50% men; median age: 84.5 years; age
      range: 80-95 years), of whom 55% were on hemodialysis and 45% were on peritoneal
      dialysis (PD). Overall life expectancy was 2.1 years. Among the 59 patients who
      died while still part of our program, 92% had a do not resuscitate order in
      place, and 46% had withdrawn from dialysis. Palliative care was consulted in 46%
      of cases. Dyspnea and pain were the two most common symptoms in the last 24 hours
      of life. Of these 59 patients, 71% died in hospital. Only 6 patients died at
      home, all of these being on home PD. End-of-life care for this elderly cohort of
      dialysis patients could be improved on several measures to meet clinical practice
      guidelines, especially with greater access to palliative care units and community
      palliative care programs.

PMID- 16983964
TI  - Association between calciphylaxis and inflammation in two patients on chronic
      dialysis.
AB  - The pathogenesis of calciphylaxis, which has a rising incidence in the chronic
      dialysis population and a high mortality rate, is poorly understood.
      Abnormalities in the calcium-phosphorus-parathyroid axis are clinically related
      to calciphylaxis, but alone, they cannot explain this condition. Here, we present
      two patients who had chronic inflammatory conditions and hyperparathyroidism and
      who developed calciphylaxis. A 41-year-old white woman on hemodialysis following
      scleroderma, hepatitis C, liver transplant, and failed kidney transplant,
      developed progressive ulcerative lower extremity calciphylaxis lasting more than
      3 years. She had evidence of severe hyperparathyroidism and elevated serum C
      reactive protein (CRP). A 39-year-old white woman on continuous ambulatory
      peritoneal dialysis for 6 years for renal failure secondary to lupus nephritis,
      with sustained lupus activity during the dialysis period, developed rapidly
      progressing ulcerative calciphylaxis of the lower and upper extremities not
      responding to adequate treatment of hyperphosphatemia and hyperparathyroidism.
      Her condition culminated in death within 2 months of the appearance of the skin
      lesions. Her serum CRP was elevated on a sustained basis before the development
      of the calciphylaxis and rose to a very high level after appearance of the skin
      lesions. Inflammation may assist in the development of calciphylaxis through
      depression of serum levels of fetuin-A, an endogenous inhibitor of calcification
      that is also a negative acute-phase reactant. The interactions between
      inflammation-mediated changes in the levels of endogenous inhibitors of
      calcification and abnormalities in calcium-phosphorus metabolism merit intensive
      study in the future as potential mechanisms of calciphylaxis.

PMID- 16983966
TI  - Peritoneal dialysis or hemodialysis? A dilemma for the nephrologist.
AB  - Selection of the initial dialysis modality is crucial in the treatment of end
      stage renal disease (ESRD) patients. Several patient- and physician-related
      factors play important roles in the decision between peritoneal dialysis (PD) and
      hemodialysis (HD). Although HD is the most common dialysis modality in the United
      States, in some studies PD has shown a survival advantage over HD, at least in
      the first 2 years of dialysis treatment, especially in non-diabetic patients and
      in young patients with diabetes. Other advantages accrue to early PD use in many
      patients. An integrated care approach with "healthy start" and PD as the initial
      renal replacement therapy, followed by timely transfer to HD once complications
      arise, may improve the long-term survival of ESRD patients.

PMID- 16983967
TI  - Acid-base profile and predictors of metabolic acidosis in patients undergoing
      peritoneal dialysis with lactate- and bicarbonate-buffered peritoneal dialysis
      solutions.
AB  - Metabolic acidosis correction is one of the goals of renal replacement therapy.
      Correction of acidosis in peritoneal dialysis (PD) may be affected by PD
      modalities such as automated PD (APD) or by new solutions containing a
      combination of bicarbonate and lactate as a buffer [bicarbonate continuous
      ambulatory PD (CAPD)]. The aim of the present study was to examine the acid-base
      status of our PD population and to compare the effects of APD, lactate CAPD, and
      bicarbonate CAPD on serum bicarbonate levels. We studied 35 stable patients
      undergoing APD (n = 15), lactate-buffered (35 mEq/L) CAPD (n = 14), and
      bicarbonate/lactate-buffered CAPD (n = 6) for 48.5 +/- 38.1 months. Most of our
      patients had serum bicarbonate levels in the normal range. In 3 patients (8%),
      HCO3 was below 22 mEq/L, and in 8 patients (22%; APD = 2, lactate CAPD = 2,
      bicarbonate CAPD = 4), HCO3 was above 28 mEq/L. We found no statistically
      significant correlations between HCO3 serum levels and PD prescription,
      peritoneal membrane characteristics, or intake of calcium carbonate and sevelamer
      hydrochloride. Patients on bicarbonate CAPD had higher HCO3 serum levels, but
      this difference disappeared when corrections for duration of dialysis, residual
      urine volume, and PD adequacy indices were applied. In the studied PD population,
      adequate correction of metabolic acidosis was achieved, as reflected in serum
      bicarbonate levels. We observed no difference in serum bicarbonate levels between
      APD and lactate CAPD patients. The new bicarbonate-buffered PD solutions are more
      biocompatible and can result in higher serum bicarbonate levels. However, a
      significant number of PD patients on bicarbonate-buffered solutions may become
      alkalotic. The clinical significance of these results needs further examination
      in prospective studies.

PMID- 16983968
TI  - Risk factors for vascular complications in patients on peritoneal dialysis.
AB  - The major cause of death in patients on peritoneal dialysis (PD) is vascular
      complications, including congestive heart failure, cerebrovascular disease, and
      myocardial infarction. To clarify the risk factors for vascular complications in
      patients on PD, we investigated the clinical course of PD in patients with and
      without cardiovascular and cerebrovascular complications. From among 327 end
      stage renal disease (ESRD) patients initiated onto PD from April 1995 to March
      2005 in the Kidney and Dialysis Center, Saitama Medical School, 8 developed de
      novo cardiovascular and cerebrovascular complications (CVD group--mean age: 58.3
      +/- 4.9 years; 5 men, 3 women). We compared data pertaining to body weight, blood
      pressure, blood chemistry, and cardiothoracic ratio (CTR) between the CVD group
      and an age- and sex-matched control group (n = 8; mean age: 57.5 +/- 4.0 years).
      At baseline, we observed no significant differences of body weight, blood
      pressure, CTR, hemoglobin, total cholesterol, triglycerides, HbA1c, or serum
      albumin between the CVD group and the control group. In the CVD group, 1 month
      before the onset of CVD, serum albumin was significantly lower than in the
      control group (2.9 +/- 0.2 g/dL vs. 3.8 +/- 0.1 g/dL, p = 0.0029). Body weight in
      the CVD group was significantly lower than in the control group (56.8 +/- 2.8 kg
      vs. 63.0 +/- 2.9 kg, p = 0.0086). No significant differences were observed in
      blood pressure, CTR, hemoglobin, total cholesterol, triglycerides, or HbA1c
      between the groups. A decrease in serum albumin after commencement of dialysis is
      an important risk factor for, and a strong predictor of vascular complications in
      patients on PD. To help prevent vascular complications, it is important to
      monitor and manage serum albumin in patients on PD.

PMID- 16983969
TI  - Serum albumin levels, an additional factor implicated in hyperparathyroidism
      outcome in peritoneal dialysis: a prospective study with paired bone biopsies.
AB  - Renal osteodystrophy encompasses several histologic subtypes, all of which can
      undergo change over time. In peritoneal dialysis (PD) patients, we studied bone
      histology and the factors influencing any changes over 1 year In 44 PD patients,
      we collected two paired bone biopsies (at baseline and after 12 months) and
      biochemical and treatment data (at baseline and every 3 months). Of the 44
      original patients, 24 completed the study. Of these 24 patients, 19 were
      initially diagnosed with adynamic bone lesion (ABL). After 1 year, 12 still had
      ABL; the other 7 had changed to high turnover bone lesion (HTBL). Another 5
      patients were initially diagnosed with HTBL. Among these, 4 still had HTBL at 1
      year; 1 had changed to ABL. In patients who changed to HTBL from ABL, serum
      albumin had increased to 4.2 +/- 0.3 g/dL at month 12 from 3.7 +/- 0.4 g/dL at
      baseline (p < 0.05). In patients who still had ABL, serum albumin did not change.
      Additionally, the percentage increase in serum albumin over the study was higher
      in HTBL patients than in ABL patients (0.1408 +/- 0.139 g/dL vs. -0.0076 +/-
      0.113 g/dL, p = 0.009). A lower likelihood of diabetes (p = 0.033) and a higher
      serum albumin [area under the curve: 0.822; 95% confidence interval (CI): 0.651
      to 0.993] identified a HTBL diagnosis at 12 months. Older age increased the
      probability of changing to ABL (OR: 1.2935; 95% CI: 1.03 to 1.67; p= 0.02). Bone
      lesions can change over time, and this change is associated with age, diabetes,
      and serum albumin. A change to HTBL was associated with improvement in serum
      albumin. Protein status is possibly a factor influencing bone lesion outcome.

PMID- 16983970
TI  - Serum markers of bone turnover in dialyzed patients grouped by level of intact
      parathyroid hormone.
AB  - We evaluated serum markers of bone turnover (BT) in patients suspected to have
      low bone turnover (LBT) given their serum level of intact parathyroid hormone
      (iPTH). Studies were carried out in 30 dialyzed patients. In 9 patients, iPTH was
      below 100 pg/mL (LBT group), and in 21, it was above 100 pg/mL (non-LBT group).
      Other measured laboratory parameters included serum concentrations of cyclase
      inactivating parathyroid hormone (CAP), osteoprotegerin (OPG), OPG ligand (OPGL),
      inorganic phosphates, total calcium, creatinine, urea, serum alkaline phosphatase
      (ALP) activity, and blood pH. The LBT group showed significantly lower levels of
      iPTH (39.0 +/- 30.7 pg/mL), CAP (23.2 +/- 16.9 pg/mL), cyclase inactive
      parathyroid hormone (CIP: 15.8 +/- 15.0 pg/mL), and total ALP (83.9 +/- 26.2
      IU/L) than did the non-LBT group (393 +/- 304 pg/mL, 268 +/- 216 pg/mL, 126 +/-
      96 pg/mL, and 202 +/- 167 IU/L respectively). We observed no significant
      differences between the groups in the other examined parameters. When results
      were adjusted for sex, age, and dialysis modality and duration, differences
      remained significant only for iPTH and CIP. Our data indicate that a serum CIP
      concentration below 25 pg/mL has a significance similar to that of an iPTH
      concentration below 100 pg/mL in determining which dialyzed patients likely have
      LBT.

PMID- 16983971
TI  - Frequency of low carnitine levels in children on dialysis.
AB  - To determine the frequency of low carnitine levels, we measured serum carnitine
      in pediatric patients on peritoneal dialysis (PD) and hemodialysis (HD). Our
      prospective cross-sectional study was conducted from September 2004 to March 2005
      in a single pediatric center, and included patients under 17 years of age who had
      been on HD or PD for more than 3 months. Patients with primary carnitine
      deficiency were excluded. A 4-day food diary was used for carnitine intake
      quantification. Serum total and free carnitine and acylcarnitine were measured.
      We compared patients with low and normal carnitine levels using the chi-square
      test, Mann-Whitney U-test, and Spearman correlation. Of 100 study patients, 70
      were on PD, and 61 were male. The median age was 13 years, and the median time on
      dialysis, 10.5 months. Median serum free carnitine was 32.75 nmol/mL. Carnitine
      levels were lower than normal in 75 patients and reached the level of deficiency
      in 29. No difference was found between the dialysis modality types for any
      fraction of carnitine. No correlation was found between the level of free
      carnitine and time on dialysis (r = -0.009, p = 0.9) or carnitine intake (r = 
      0.84, p = 0.4). In conclusion, the frequency ofl ow serum carnitine among
      pediatric patient on dialysis is high.

PMID- 16983972
TI  - [Possible interaction of environment and genetic factors in work-related
      diseases: the case of hypertension].
AB  - BACKGROUND: Cardiovascular diseases are the most important cause of death and
      invalidity during the course of working life. The major risk factor for
      cardiovascular diseases is arterial hypertension, a typical example of
      multifactorial and polygenic disease, involving genetic, environmental, and
      demographic factors. OBJECTIVES: A review of studies performed sofar on
      hypertension which can be also defined as a work-related disease. METHODS:
      Several studies on association or linkage analysis showed an association between
      genetic polymorphisms and increased risk of hypertension. RESULTS: Till now no
      studies have identified one or more "major" candidate genes involved in the
      pathogenesis of hypertension. Recently the interaction between genetics and
      environment have attracted much interest since the genotypes predisposingfor
      hypertension have different effects according to the patient's environment and
      life style. CONCLUSIONS: It is likely that the aspects covered in this review
      will, in the near future, be studied more extensively. The identification of any
      correlations between genes and environment will also be influenced by the
      accuracy in measuring environmental exposure, where the occupational physician
      will play a significant role.

PMID- 16983973
TI  - [Assessment of efficacy and economic impact of an influenza vaccination campaign
      in the personnel of a health care setting].
AB  - INTRODUCTION: Although vaccination against influenza is a well-established
      practice among the elderly in rest homes, in community-dwelling elderly people
      and in persons with underlying medical conditions associated with a high risk of
      complications, vaccination of workers is not always considered cost-effective,
      even though influenza is high on the list of diseases of public health
      importance. The aim of this study was to evaluate the efficacy and the cost
      benefit ratio of an influenza vaccination campaign in health care workers (HCW)
      of a teaching hospital. METHODS: A group of 423 HCW vaccinated against influenza
      during the 2002-2003 winter season was compared with a group of subjects not
      vaccinated, matched for sex and working area. The following outcomes were
      considered: (i) prevalence of influenza-like illness (ILI); (ii) days of absence
      from work due to ILL The cost-benefit ratio was calculated with a model using the
      following indices. indirect benefits (IB), indirect non medical costs (IC) and
      direct costs (DC). RESULTS: The prevalence of ILI in the non vaccinated group
      (102 cases out of 423 subjects, 24%) was significantly increased (p < 0.001)
      compared with vaccinated subjects (64 cases out of 423, 15%). Working days lost
      for ILI were 516 in the non-vaccinated group versus 315 reported in the
      vaccinated group. Economic impact evaluation showed a cost of Euro 35,786.88 in
      vaccinees and of Euro 57,759.52 in the non-vaccinees. The resulting IB was Euro
      21,078.64. The DC and IC for vaccination were Euro 2,463.29 and Euro 2,172.53
      respectively. The overall cost-benefit ratio (IB/DC+IC) was 4.5. DISCUSSION: The
      study shows that the influenza vaccination campaign was effective in preventing
      the influenza syndrome in HCW The economic impact assessment shows a cost-saving
      with an important cost-benefit ratio. This study suggests that a continuous
      effort should be recommended to increase the compliance of HCW with vaccination
      practice both to reduce their chance of becoming infected and for the economic
      benefits for healthy working adults.

PMID- 16983974
TI  - Malignant mesothelioma of the pleura among seafarers.
AB  - BACKGROUND: A large amount of data indicates that seafarers are at risk for
      asbestos disease. OBJECTIVES: To trace the outlines of pleural mesothelioma among
      seafarers. METHODS: Pleural mesotheliomas diagnosed among seamen in the Trieste
      Monfalcone area, Italy, in the period 1973-2003, were reviewed. RESULTS: The
      series comprised 50 men aged between 53 and 91 years (mean age 75.7 years). The
      diagnosis of mesothelioma was confirmed by necropsy in 38 cases. The patients had
      served in the Italian Navy (24 persons), in the merchant navy (17 persons), or in
      both (9 persons). The trades were various including engine room as well as deck
      personnel. Asbestos bodies were detected on routine lung sections in 55% of the
      necropsy cases. Asbestos bodies isolated from the lungs in three cases ranged
      between 2100 and 7000 bodies per gram of dried tissue. Latency periods ranged
      between 33 and 72 years (mean 56.1 years). CONCLUSIONS: When compared with
      shipyard workers, the seamen with mesothelioma show signs of less intense
      exposure to asbestos, and longer latency periods. Mesothelioma in seamen should
      be considered as an occupational disease.

PMID- 16983975
TI  - [Health surveillance of health care workers suffering from neurological,
      psychiatric or behavioural disorders].
AB  - INTRODUCTION: Health care workers (HCWs) suffering from psychiatric or
      neurological disorders, alcohol or drug addiction, may pose a risk for the health
      and safety of patients. The occupational health specialist charged of medical
      surveillance of hospital workers (the so-called "Competent Physician") often
      needs to recognize functional impairment in HCWs. CASE REPORT: Cases of
      impairment in HCWs are reported, and management criteria are discussed, in order
      to define effective strategies to deal with the problem. DISCUSSION: Alcoholism
      and other drug addictions are the most common causes of impairment, followed by
      emotional impairment, neurological and other physical disabilities. The primary
      responsibility of protecting the public, should be achieved while at the same
      time maintaining HCWs at work whenever possible. CONCLUSION: Critical key-points
      are identified, and suggestions for management of functionally impaired HCWs are
      given.

PMID- 16983976
TI  - [Occupational allergic IgE-mediated disease from Boletus edulis: case report].
AB  - BACKGROUND: Fungal components can cause allergic symptoms either through
      inhalation, ingestion or contact. Allergic disease from occupational exposure to
      Boletus edulis (BE) has only seldom been reported. OBJECTIVES: Report on a female
      worker who developed respiratory and skin symptoms from occupational exposure to
      BE in selecting and packing dried mushrooms. She never had symptoms after eating
      mushrooms. METHODS: An environmental study was performed by personal air
      samplings and settled dust collection. The RAST-inhibition procedure was used to
      detect BE allergen potency in collected dust. The subject underwent clinical
      evaluation, spirometry, skin prick-tests, RAST methacoline and specific
      inhalation challenge with BE extract. A follow-up study was made 2, 4 and 8
      months after the first evaluation and after cessation of exposure. RESULTS: BE
      allergens were found in the settled dust. Clinical examination showed eczema on
      the face and hands. The worker had hyper-eosinophilia, bronchial hyper
      responsiveness to methacoline, no allergy to common inhalants and foods, positive
      prick-test and RAST for BE. The specific inhalation challenge induced broncho
      constriction. At follow-up we observed a progressive clinical and functional
      improvement. CONCLUSIONS: Our data show that BE can induce cutaneous and
      respiratory symptoms from occupational exposure to dried mushroom dusts. The
      pathogenesis is an IgE-allergy. Our patient had no symptoms from ingestion, which
      supports the hypothesis that respiratory allergy is due to mushroom antigens that
      differ from those involved in food-related allergic reactions.

PMID- 16983978
TI  - [Compendium of the Section of Occupational Medicine of the European Union of
      Medical Specialists (UEMS)].

PMID- 16983977
TI  - [Effectiveness studies in the Italian Society of Occupational Medicine and
      Industrial Hygiene congresses (1989-2003)].
AB  - BACKGROUND: Knowledge of the results of studies on effectiveness of preventive
      interventions is a fundamental requirement in occupational medicine. OBJECTIVES:
      The aim of this review was to identify Italian scientific production regarding
      this issue in the proceedings of the Italian Society of Occupational Medicine and
      Industrial Hygiene congresses over the last fifteen years. METHODS: An initial
      selection of the communications on intervention effectiveness studies was
      performed on the basis of titles, aims, tables and figures of each single
      presentation. A further selection was made via full reading of the previously
      selected communications. The selected articles were classified by type of
      strategy discussed, production sector, study design and several other criteria.
      RESULTS: 108 studies were selected out of the 3215 papers (3.4%) published in the
      congress proceedings examined (1989-2003). More than half of these discussed
      technical control strategies. In the vast majority of cases, the study design was
      a pre- and post-evaluation of effectiveness, and the 6 (non-randomised) trials
      concerned vaccination programmes. Almost a quarter of the studies on accident
      prevention regarded the effectiveness of training programmes. Only 5 studies
      could be detected in Medline as articles later published in international
      journals. CONCLUSIONS: On the basis of the Italian Society of Occupational
      Medicine congress proceedings over the last 15 years, the percentage of
      communications concerning effectiveness of preventive interventions in
      occupational health was 3.4%. Intervention effectiveness papers published in
      congress proceedings seem to reveal a quite unexpected production of
      effectiveness evaluation studies. Nonetheless, recommendations need to be made to
      improve study design and to promote effective prevention and control strategies.

PMID- 16983979
TI  - [Prevention and management of the risk of biomechanical work overload diseases --
      evaluation of the risk, health supervision and ergonomic planning. Educational
      courses, 2006-2007].

PMID- 16983980
TI  - [Meeting of the Group La.R.A. (Workers risky for the others].

PMID- 16983981
TI  - [Constitutionum epidemicarum mutinensium annorum quinque. Edition Secunda. 1714].

PMID- 16983982
TI  - [Prevalence of HPV in sex workers in Durango, Mexico].

PMID- 16983983
TI  - [Influenza, an opportunity for prevention and control].

PMID- 16983984
TI  - Hepatitis A: the burden among Latino children in California.
AB  - OBJECTIVE: To determine the prevalence of Hepatitis A within subpopulations of
      southern California counties. MATERIAL AND METHODS: Age and race/ethnic-specific
      hepatitis A rates were derived from the California Department of Health Services
      Surveillance and Statistics Section for 1996-2001 and from demographic data of
      the California Department of Finance. RESULTS: 2.3 million Latino children (aged
      0-14 years) in five southern California counties had a rate of 31.1 cases per
      100,000, five times higher than the non-Hispanic white rate. CONCLUSION: The CDC
      Advisory Committee on Immunization Practices recommends routine vaccination for
      children with "very high" rates of hepatitis A. The annual prevalence of
      hepatitis A in California, especially in southern California, met the CDC's "very
      high" definition, therefore Latino children in these counties should be
      considered for routine childhood hepatitis A vaccination. As health has no
      borders, this issue should be addressed by the public health services of both,
      the United States' and Mexico's public health services.

PMID- 16983985
TI  - [Prevalence and risk factors related to sale of cigarettes to minors in stores in
      Mexico City].
AB  - OBJECTIVE: To identify the prevalence of the sale of cigarette to minors in
      stores in Mexico City. MATERIAL AND METHODS: A cross-sectional study was done
      applying a questionnaire to salespersons in stores that sell cigarettes. The
      SCINCE 2000 from INEGI was used to select and sample two Basic Geostatistical
      Areas (AGEB) per Delegation and a census of stores was carried out. RESULTS: A
      total of 577 stores were visited, 73% sold cigarettes to minors, 58% sell loose
      cigarettes, only 2.6% asked the buyer's age, and 1.2% requested identification.
      Among the salespersons, 51% were men, 37% had secondary school studies, 57% were
      smokers, 42% had children underage, and 99% knew that the sale of cigarettes to
      minors is prohibited. The multivariate analysis established an explicative model
      and it was discovered that when the salesperson was male or if the cigarettes
      were sold individually the probability of sale was 2 and 5 times higher
      respectively. CONCLUSIONS: The sale of cigarettes to minors in Mexico City is not
      associated with the personal characteristics of the salespersons or with the
      stores.

PMID- 16983986
TI  - [Validation of an instrument to monitor food insecurity in Sierra de Manantlan,
      Jalisco].
AB  - OBJECTIVE: To validate a version of the Food Security Scale (FSS) in communities
      located in Sierra de Manantlan, Jalisco. MATERIAL AND METHODS: Using focus
      groups, the FSS was modified to fit the Mexican context. Subsequently, a survey
      was applied to women with pre-school aged children. The FSS was validated in
      correlation with a household food inventory and the dietary variety of the
      individual being interviewed. The interview also included a socioeconomic
      questionnaire. RESULTS: Forty-four percent of the households reported mild food
      insecurity, 33% reported moderate hunger and 19.7% reported severe hunger. Food
      insecurity was significantly and inversely correlated with the number of food
      items in the household (r=-0.36**), animal source foods (r=-0.28**), dairy
      products (r=-0.25*), processed foods (r=-0.37**), fruits (r=-0.21*), and
      vegetables (r=-0.28**); *p<0.05, **p< 0.01. Food insecurity was also associated
      with low dietary variety (r=-0.23, p=0.02). These associations were maintained in
      multivariate models. CONCLUSIONS: The FSS is a useful tool for monitoring food
      insecurity in rural regions of Jalisco.

PMID- 16983987
TI  - [The prevalence of high-risk HPV infection in pregnant women from Morelos,
      Mexico].
AB  - OBJECTIVE: Some studies suggest the possibility that the physiological process of
      pregnancy modifies certain characteristics of the mother, increasing the risk of
      both, infection and persistence of infection with HPV. This association, however,
      has not been firmly established. This study seeks to determine the prevalence of
      oncogenic HPV infecton in a sample of pregnant Mexican women and its possible
      risk factors. MATERIAL AND METHODS: A cross-sectional study was conducted using a
      sample of 274 pregnant women sought first level of care services during the year
      2000 at the antenatal clinic of the Mexican Institute of Social Security (IMSS)
      in Cuernavaca, Morelos, Mexico. Samples of vaginal cells were obtained through
      self-collected specimens, for the high-risk HPV DNA test using the Hybrid Capture
      2 test (HC2). A structured questionnaire was administered regarding
      sociodemographic, gynecologic, obstetric and sexual behavior characteristics.
      RESULTS: The mean age was 25.7 years. The average time of pregnancy when the
      study was conducted was 6 months. The principal risk factors associated with high
      risk HPV infection were: ages between 20 and 29 (OR= 2.82; CI 95% 1.02-7.76)),
      age 30 and over (OR= 6.85,CI 95% 1.22-38.2); partners having sexual relations
      with other partners (OR= 2.05; CI 95% 1.2-3.7)); schooling less than 6 years (OR=
      1.68 CI 95% 0.7-4.3); number of lifetime sexual partners > 2 (OR= 1.54 CI 95% 0.7
      3.4); and current smoking (OR= 1.6 CI 95% 0.6-5.0). CONCLUSIONS: Our findings
      show a higher prevalence of high-risk HPV infection in pregnant women, more than
      double, that reported in studies of non-pregnant women. The associated risk
      factors are similar to those of the non-pregnant population. Follow-up in these
      women is recommended in order to evaluate the persistence or regression of the
      infection.

PMID- 16983988
TI  - [Financial protection in health: Mexico, 1992 to 2004].
AB  - OBJECTIVE: To document trends in financial protection in the health care system
      in Mexico between 1992 and 2004, applying a series of indicators that measure
      catastrophic and impoverishing health spending and the Index of Fairness in
      Financial Contributions. MATERIALS Y METHODS: This study uses the biannual time
      series of the Survey of Household Income and Expenditures (ENIGH) spanning the
      period 1992 to 2004. The methodologies seek to measure the level and distribution
      of the burden of health care finance on households, and the financial protection
      offered to them by the health care system. Four indicators are presented: 1) the
      Index of Fairness in Financial Contributions, 2) the proportion of households
      with catastrophic health expenditure, 3) the proportion of households with
      impoverishment due to health spending and 4) the sum of the proportion of
      households with catastrophic or impoverishing health spending, which is referred
      to as excessive health spending. The analysis presented in this document is
      descriptive, leaving for later studies a deeper analysis of causal aspects.
      RESULTS: The number of families that suffer impoverishment due to health spending
      increased from 5.2% in 1992, reached a high of 9.9% in 1996, and then gradually
      declined to 1.8% by 2004. The proportion of households with catastrophic expenses
      began at 2.8% in 1992, increased to 4.2% in 1998 and then fell to a level of 2.6%
      in 2004. The improvements from 2000 on are concentrated among the uninsured
      population, families affiliated to Popular Health Insurance, and households in
      the poorest two quintiles of the income distribution. CONCLUSIONS: The patterns
      over time in excessive health spending reflect a worsening during periods of
      economic crisis, post-crisis recovery, and a sustained improvement beginning in
      the year 2000. The data suggest that part of the reduction in the number of
      households with excessive health spending is due to the extension of financial
      protection for Mexican families through the Popular Health Insurance, while
      another part is associated with a decline in poverty. In addition,this paper
      documents an important relationship between economic trends and catastrophic and
      impoverishing health spending, suggesting the importance of financially
      protecting families through health insurance. Financial protection assists in
      guaranteeing that when economic crisis--of a country or of a family--coincides
      with illness, health care payments do not become the cause of a long or permanent
      period of impoverishment for households.

PMID- 16983989
TI  - [Cultural dimensions of the childhood primary health care delivery from the
      mothers' perceptions in the Araucania-Chile].
AB  - OBJECTIVE: To explore the cultural dimensions of the childhood primary health
      care delivery process from the mothers' perceptions in the Araucania region of
      Chile. MATERIAL AND METHODS: Qualitative study performed in the year 2003 within
      the zone with the highest ethnicity rate of the country. Ninety four Mapuche and
      non-Mapuche mothers agreed to be in depth interviewed. RESULTS: The analysis drew
      three cultural dimensions: a) Explanatory models of disease were associated with
      cultural, political-economy, and environmental factors; b) The therapeutic
      itinerary blends indigenous, popular, and biomedical resources and; c) Health
      care delivery process lacks of cultural competence. CONCLUSIONS: The mothers
      explain their children diseases articulating religious, magic, and natural (hot,
      cold, humidity) causes. The main challenge of the primary healthcare delivery
      process is to overcome the communicational barriers due to the social and
      linguistic differences between mothers and health care providers.

PMID- 16983990
TI  - [Maternal overweight and obesity in Mexican school-age children. National
      Nutrition Survey, 1999].
AB  - OBJECTIVE: To assess the effects of maternal overweight and obesity as risk
      factors for overweight and obesity in Mexican school-age children (5 to 11 years
      old) who participated in the National Nutrition Survey 1999 (NNS-99). MATERIAL
      AND METHODS: Information obtained by the NNS-99 was used to evaluate the
      relationship between maternal overweight and obesity and overweight or obesity in
      school-age children. Multivariate logistic regression analysis was used. RESULTS:
      A total of 9 259 children were studied. The prevalence of overweight or obesity
      was 19%, according to the criteria suggested by Cole.Thirty-nine percent of
      mothers were overweight and 26.4% were obese. After controlling for age, gender,
      and other sociodemographic characteristics, children of overweight mothers had a
      1.9 times higher risk of being obese (95%CI 1.62-2.18), and children of obese
      mothers had a 3.4 times higher risk of being obese (95%CI 2.96-4.00), compared to
      children of mothers with normal BMI. CONCLUSION: Maternal overweight and obesity
      are risk factors for overweight or obesity in Mexican school-age children.
      Interventions to prevent obesity in children should be aimed towards promoting
      family lifestyle changes and modifying obesigenic environments.

PMID- 16983991
TI  - [Costs of medical care attributable to tobacco consumption at the Mexican
      Institute of Social Security (IMSS), Morelos].
AB  - OBJECTIVE: To estimate the cost of medical care for the major diseases
      attributable to tobacco consumption at the IMSS, Morelos. MATERIAL AND METHODS: A
      cost of illness (COI) analysis was carried out from the perspective of the health
      provider. An expert panel characterized medical care in primary and secondary
      care levels according to severity of disease. The smoking attributable fraction
      (SAF) by disease was used to derive costs attributable to tobacco consumption.
      The unitary cost was valuated in 2001 Mexican pesos (MP). RESULTS: The estimated
      annual average cost of medical care (diagnosis and first year of treatment) was
      79,530 MP for acute myocardial infarction (AMI); 73,303 MP for chronic
      obstructive pulmonary disease (COPD); and 102,215 MP for lung cancer (LC). The
      annual total cost of medical care for IMSS was 147,390 688 MP. The total annual
      cost of medical care attributable to tobacco consumption corresponds to dollars
      124 million MP, which is equivalent to 7.3% of the annual budget of the Morelos
      Delegation. CONCLUSIONS: These results confirm the high medical costs associated
      with smoking. A repetition of this study at the national level is recommended in
      order to support decision-makers in strengthening public policies to control
      tobacco use in Mexico.

PMID- 16983992
TI  - [Gene therapy with cytokines against cervical cancer].
AB  - Gene therapy is an excellent alternative for treatment of many diseases. Capacity
      to manipulate the DNA has allowed direct the gene therapy to correct the function
      of an altered gene, to increase the expression of a gene and to favour the
      activation of the immune response. This way, it can intend the use of the DNA
      like medication able to control, to correct or to cure many diseases. Gene
      therapy against cancer has an enormous potential, and actually the use of the DNA
      has increased to control diverse cancer in animal models, with very encouraging
      results that have allowed its applications in experimental protocols in human.
      This work concentrates a review of the foundations of the gene therapy and its
      application on cervical cancer, from the point of view of the alterations of the
      immune system focused on the tumour micro-environment, and the use of the
      cytokines as immunomodulators.

PMID- 16983993
TI  - Role of oxidative stress in experimental sepsis and multisystem organ
      dysfunction.
AB  - Massive increase in radical species can lead to oxidative stress, promoting cell
      injury and death. This review focuses on experimental evidence of oxidative
      stress in critical illnesses, sepsis and multisystem organ dysfunction. Oxidative
      stress could negatively affect organ injury and thus overall survival of
      experimental models. Based on this experimental evidence, we could improve the
      rationale of supplementation of antioxidants alone or in combination with
      standard therapies aimed to reduce oxidative stress as novel adjunct treatment in
      critical care.

PMID- 16983994
TI  - Ferritin oxidation and proteasomal degradation: protection by antioxidants.
AB  - The accumulation of oxidatively damaged proteins is a well-known hallmark of
      aging and several neurodegenerative diseases including Alzheimer's, Parkinson's
      and Huntigton's diseases. These highly oxidized protein aggregates are in general
      not degradable by the main intracellular proteolytic machinery, the proteasomal
      system. One possible strategy to reduce the accumulation of such oxidized protein
      aggregates is the prevention of the formation of oxidized protein derivatives or
      to reduce the protein oxidation to a degree that can be handled by the
      proteasome. To do so an antioxidative strategy might be successful. Therefore, we
      undertook the present study to test whether antioxidants are able to prevent the
      protein oxidation and to influence the proteasomal degradation of moderate
      oxidized proteins. As a model protein we choose ferritin. H2O2 induced a
      concentration dependent increase of protein oxidation accompanied by an increased
      proteolytic susceptibility. This increase of proteolytic susceptibility is
      limited to moderate hydrogen peroxide concentrations, whereas higher
      concentrations are accompanied by protein aggregate formation. Protective effects
      of the vitamin E derivative Trolox, the pyridoindole derivative Stobadine and of
      the standardized extracts of flavonoids from bark of Pinus Pinaster Pycnogenol
      and from leaves of Ginkgo biloba (EGb 761) were studied on moderate damaged
      ferritin.

PMID- 16983996
TI  - Oxidative and nitrative modifications of enkephalins by reactive nitrogen
      species.
AB  - The interaction of Leucine-enkephalin (Leu-enkephalin) with reactive nitrogen
      species has been investigated. Reactive nitrogen species are capable of nitrating
      and oxidizing Leu-enkephalin. HPLC analysis shows the formation of two major
      enkephalin derivatives by peroxynitrite. The tyrosine amino-terminal residue of
      Leu-enkephalin is converted either to 3-nitrotyrosine thus producing
      nitroenkephalin and to dityrosine by dimerization with the production of an
      enkephalin dimer. The evidence of the formation of the nitroenkephalin and of the
      enkephalin dimer--dienkephalin--was achieved by electrospray ionisation mass
      spectrometry. In addition to peroxynitrite, the methylene blue photosensitized
      oxidation of enkephalin in the presence of nitrite leads to the formation of the
      nitrated peptide. Moreover, the nitropeptide can be also obtained by peroxidase
      generated nitrogen reactive species.

PMID- 16983995
TI  - A novel neuroprotective agent with antioxidant and nitric oxide synthase
      inhibitory action.
AB  - N(alpha)-vanillyl-N(omega)-nitroarginine (N - 1) that combines the active
      functions of natural antioxidant and nitric oxide synthase inhibitor was
      developed for its neuroprotective properties. N - 1 exhibited protective effects
      against hydrogen peroxide-induced cell damage and the inhibitory effect on nitric
      oxide 'NO' production induced by calcium ionophore in NG 108-15 cells. N - 1
      inhibited the constitutive NOS isolated from rat cerebellar in a greater extent
      than constitutive NOS from human endothelial cells. Low binding energy (-10.2
      kcal/mol) obtained from docking N - 1 to nNOS supported the additional mode of
      action of N - 1 as an nNOS inhibitor. The in vivo neuroprotective effect on
      kainic acid-induced nitric oxide production and neuronal cell death in rat brain
      was investigated via microdialysis. Rats were injected intra-peritonially with N 
      1 at 75 micromol/kg before kainic acid injection (10 mg/kg). The significant
      suppression effect on kainic acid-induced NO and significant increase in
      surviving cells were observed in the hippocampus at 40 min after the induction.

PMID- 16983997
TI  - DNA oxidative damage and strand breaks in young healthy individuals: a gender
      difference and the role of life style factors.
AB  - The aim of this study was to analyze background levels of DNA damage in young (19
      31 years) non-smoking individuals and to correlate damage to gender and life
      style. DNA single strand breaks (SSB) and alkali labile sites (ALS) were measured
      in 99 subjects living in Stockholm, Sweden. Further, oxidative DNA damage was
      analyzed using the DNA repair glycosylase FPG as well as HPLC-ECD for specific
      analysis of 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG). We found that males had
      higher (P < 0.001) levels of SSB + ALS than females, but no difference was seen
      for oxidative lesions. There was no correlation between FPG sites and 8-oxodG.
      For females, there was a positive correlation between FPG levels and body mass
      index and a negative correlation between SSB + ALS and fruit intake. We conclude
      that the background level of oxidative DNA damage, analyzed with improved
      methods, is low and that gender, fruit intake and BMI can affect DNA damage.

PMID- 16983998
TI  - Hindlimb unloading decreases thioredoxin-related antioxidant proteins and
      increases thioredoxin-binding protein-2 in rat skeletal muscle.
AB  - To investigate role(s) of thioredoxin-related antioxidant proteins in disuse
      muscle atrophy, we examined the levels of thioredoxin-1 (Trx-1), peroxiredoxin
      3/SP-22 (Prx-3) and thioredoxin-binding protein-2 (TBP-2) in rat soleus muscle
      subjected to hindlimb unloading (HU) for 2, 4, 7 or 14 days. The muscle weight
      loss was initially observed on day 4. The increases in aclorein- and
      malondialdehyde-modified proteins, and the decreases in the levels of Trx-1, Prx
      3 and Mn-SOD were observed in the late phase of muscle atrophy, whereas, the
      increase in mRNA expression of TBP-2, a negative regulator of thioredoxin,
      preceded muscle atrophy. These findings suggest that the decrease of those
      antioxidant proteins, particularly a marked decrease of Trx-1, may be responsible
      for the enhanced oxidative damage during the late phase of disuse muscle atrophy.
      Furthermore, the increase in TBP-2 preceding the muscle atrophy may suppress the
      thioredoxin-mediated redox signaling, which can be an initial trigger leading to
      disuse muscle atrophy.

PMID- 16983999
TI  - Impact of diabetic polyneuropathy and cardiovascular autonomic neuropathy on the
      excretion of urinary 8-epi-PGF2alpha and its metabolites (2, 3-dinor and 2, 3
      dinor-5, 6-dihydro).
AB  - The objective of this study was to establish if diabetes in the presence of
      polyneuropathy (PN) and/or cardiovascular autonomic neuropathy (CAN) is
      associated with alterations in the amounts of 8-epi-PGF2alpha (IP) and its
      metabolites including 2, 3-dinor-8-epi-PGF2alpha (dinor-IP) and 2, 3-dinor-5, 6
      dihydro-8-epi-PGF2alpha (dinor-dihydro-IP) in urine. Mass spectrometric
      separation showed that excretion of IP was similar in the PN + /CAN- and PN+/CAN+
      groups but higher than in the PN-/CAN- group (n = 103, 22 and 60, respectively; P
      < 0.05). By contrast, excretion of dinor-IP or dinor-dihydro-IP were similar in
      the PN-/CAN- and PN+/CAN- groups but higher than in PN+/CAN+ group. Correlations
      were obtained between IP and dinor-IP or dinor-dihydro-IP (r = 0.30; P < 0.001
      and r = 0.31; P < 0.001, respectively). A significant association was also
      observed between dinor-IP and dinor-dihydro-IP (r = 0.48; P < 0.001). In
      conclusion, these biomarkers should prove useful in studies evaluating the impact
      of therapeutic drugs or antioxidant interventions aimed at delaying the onset of
      diabetic complications.

PMID- 16984000
TI  - A spectroscopic study of some of the peptidyl radicals formed following hydroxyl
      radical attack on beta-amyloid and alpha-synuclein.
AB  - There is clear evidence implicating oxidative stress in the pathology of many
      neurodegenerative diseases. Reactive oxygen species (ROS) are the primary
      mediators of oxidative stress, and hydrogen peroxide, a key ROS, is generated
      during aggregation of the amyloid proteins associated with some of these
      diseases. Hydrogen peroxide is catalytically converted to the aggressive hydroxyl
      radical in the presence of Fe(II) and Cu(I), which renders amyloidogenic proteins
      such as beta-amyloid and alpha-synuclein (implicated in Alzheimer's disease (AD)
      and Parkinson's disease (PD), respectively) vulnerable to self-inflicted hydroxyl
      radical attack. Here, we report some of the peptide-derived radicals, detected by
      electron spin resonance spectroscopy employing sodium 3,5-dibromo-4
      nitrosobenzenesulfonate as a spin-trap, following hydroxyl radical attack on
      Abeta(1-40), alpha-synuclein and some other related peptides. Significantly, we
      found that sufficient hydrogen peroxide was self-generated during the early
      stages of aggregation of Abeta(1-40) to produce detectable peptidyl radicals, on
      addition of Fe(II). Our results support the hypothesis that oxidative damage to
      Abeta (and surrounding molecules) in the brain in AD could be due, at least in
      part, to the self-generation of ROS. A similar mechanism could operate in PD and
      some other "protein conformational" disorders.

PMID- 16984001
TI  - Radical scavenging and NO-releasing properties of selected beta-adrenoreceptor
      antagonists.
AB  - It is claimed that novel beta-adrenolytic drugs possess superior antioxidant
      properties as compared to classical selective or non-selective beta-adrenoceptor
      antagonists. Here we tested this notion by analyzing radical scavenging
      properties of selected beta-adrenolytic drugs and their ability to release nitric
      oxide in biological preparations. Selective beta1-adrenolytics such as nebivolol,
      atenolol, metoprolol and non-selective beta-adrenolytics with alpha1-receptor
      blocking properties such as carvedilol and labetalol were chosen for analysis. NO
      releasing properties of nebivolol and carvedilol distinguished third generation
      beta-adrenolytics from their older counterparts while the reactivity towards
      hydroxyl and peroxyl radicals discerns only carvedilol but not nebivolol. Thus,
      superior clinical efficacy of third generation beta-adrenolytics may be related
      to their ability to release NO rather then to their direct antioxidant
      properties.

PMID- 16984002
TI  - Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta
      thalassemia red blood cells.
AB  - Antioxidant phytochemicals are investigated as novel treatments for supportive
      therapy in beta-thalassemia. The dietary indicaxanthin was assessed for its
      protective effects on human beta-thalassemic RBCs submitted in vitro to oxidative
      haemolysis by cumene hydroperoxide. Indicaxanthin at 1.0-10 microM enhanced the
      resistance to haemolysis dose-dependently. In addition, it prevented lipid and
      haemoglobin (Hb) oxidation, and retarded vitamin E and GSH depletion. After ex
      vivo spiking of blood from thalassemia patients with indicaxanthin, the
      phytochemical was recovered in the soluble cell compartment of the RBCs. A
      spectrophotometric study showed that indicaxanthin can reduce perferryl-Hb
      generated in solution from met-Hb and hydrogen peroxide (H2O2), more effectively
      than either Trolox or vitamin C. Collectively our results demonstrate that
      indicaxanthin can be incorporated into the redox machinery of beta-thalassemic
      RBC and defend the cell from oxidation, possibly interfering with perferryl-Hb, a
      reactive intermediate in the hydroperoxide-dependent Hb degradation.
      Opportunities of therapeutic interest for beta-thalassemia may be considered.

PMID- 16984003
TI  - Natural vitamin E alpha-tocotrienol: retention in vital organs in response to
      long-term oral supplementation and withdrawal.
AB  - The natural vitamin E tocotrienol (TCT) possesses biological properties not
      shared by tocopherols (TCP). Nanomolar alpha-TCT, not alpha-TCP, is potently
      neuroprotective (JBC 275:13049; 278:43508; Stroke 36:2258). The report that the
      affinity of TTP to bind (alpha-TCT is an order of magnitude lower than that for
      alpha-TCP questions the bioavailability of orally taken TCT to tissues. Oral
      supplementation of TCT for 3 years in nine generations of female and male rat was
      studied. Ten vital organs were examined. To gain insight into the turnover of
      alpha-TCT in tissues, a subset of supplemented rats was moved to vitamin E
      deficient diet for 7 weeks. Orally supplemented alpha-TCT was delivered to all
      vital organs including the brain and spinal cord in significant amounts. In
      organs such as the skin, adipose and gonads the maximum level of alpha-TCT
      achieved in response to supplementation was folds higher than baseline values of
      alpha-TCP in rats maintained on laboratory chow. Females had higher levels of
      alpha-TCT compared to matched tissues of corresponding males. To gain insight
      into how quickly alpha-TCT is metabolized in the tissues, washout of alpha-TCT
      from vital organs was examined. alpha-TCT accumulated in vital organs over more
      than 2 years was almost completely lost in less than 2 months when the
      supplementation was stopped. This is in sharp contrast with findings related to
      alpha-TCP retention. The ability of long-term oral supplementation to maintain
      and elevate alpha-TCT levels in vital organs together with the rapid elimination
      of the intact vitamin from all organs studied underscores the need for continuous
      oral supplementation of TCT.

PMID- 16984004
TI  - [Devices for the relief and evaluation of pain: preface and comments].
AB  - Pain is the most popular complaint since the appearance of the human on earth, a
      very unpleasant feeling sometimes difficult to be treated. Therefore, we have
      many patients who complain of pain in our hospitals or clinics. When a patient
      with pain visits our institution, first of all, we must evaluate the grade of
      pain, and then start to treat the pain of the patient. Of course, we have many
      devices available to treat the patient with pain. In the following special
      articles, device for evaluation of pain, spinal stimulation device, device for
      electrical current therapy (ECT), LASER device for chronic and acute pain,
      epiduroscopy for lumbago, as well as disposable infusion pump for postoperative
      pain and cancer pain are described. The mechanism of pain may be understood by
      patients themselves. However, devices in these articles are very useful for the
      treatment of pain, especially intractable pain. I feel very happy if these
      articles contribute greatly for the treatment of patients with pain.

PMID- 16984005
TI  - [Measurement of clinical pain intensity: quantitative sensory testing].
AB  - Pain is a private internal event, the degree of which can not be evaluated
      directly by others. The measurement of the nociceptive pain threshold may apply
      to the evaluation of the degree of the pain. The instruments using mechanical and
      electrical stimulation are available for the clinical application. Thermotest
      allows the testing of quantitative evaluation of thermal thresholds such as heat,
      cold, and heat and cold pain sensation. A machine for the thermotest using
      radiant heat and contact heat is available in Japan. There is an instrument using
      puncturing stimulus and pressure stimulus for a mechanical stimulation. A
      puncturing stimulus is suitable for the clinical use with a handy instrument such
      as von Frey filaments and needle type algometry. In clinical practice, the
      pressure algometry is usually applied over a bony surface or over the muscle. The
      method seems to be well suited for the evaluation of pain in musculoskeletal
      disorders. The electrical stimulation test provides a quantitative measure of
      pain tolerance to a transcutaneous stimulation, neuroselective for large and
      small myelinated and unmyelinated nerve fibers. There are characteristics
      including advantages and faults in each method, and the method of measurement
      corresponding to the purpose and application is important.

PMID- 16984006
TI  - [Equipment for spinal cord stimulation].
AB  - Spinal cord stimulation has gained widespread popularity for the treatment of
      pain. This literature discribed our equipments, methods, patient selection, and
      operative procedures for spinal cord stimulation.

PMID- 16984007
TI  - [Equipment for electro-convulsive therapy].
AB  - ECT (electro-convulsive therapy) has been used for the treatment of depressive
      patients. First it was applied in patients only with sedatives without muscle
      relaxants, but now we employ muscle relaxants to avoid convulsion and its
      complications. It is called modified ECT (mECT). General anesthesia using muscle
      relaxant for ECT is now increasingly employed in Japan. Furthermore, there are
      some reports that ECT is effective not only in depressive patients but in chronic
      pain patients. This is why anesthesiologists are especially interested in ECT. In
      this chapter, clinical application, equipment and complications of ECT are
      discussed.

PMID- 16984008
TI  - [Equipment for low reactive level laser therapy including that for light
      therapy].
AB  - Equipments used for light therapy include machinery used for irradiation by low
      reactive level laser, xenon light and linear polarized infra-red ray. Low
      reactive level laser is divided into two types of laser according to the medium
      by which laser is obtained ; semiconductor laser and helium-neon laser. Low
      reactive level laser has only one wave length and produces analgesia by action of
      light itself. On the other hands, Xenon light and linear polarized infra-red ray
      produce analgesia by warming effect induced by light in addition to the action of
      light itself. There are four methods of irradiation by these light sources;
      irradiation of acupuncture points, of trigger points, along nerves causing pain
      and of stellate ganglion area. Indication for light therapy includes various
      kinds of diseases such as herpes zoster, post herpetic neuralgia, cervical pain,
      lumbago due to muscle contracture, complex regional pain syndrome, arthralgia
      etc. However, we have to know that light therapy does not exert analgesic effects
      equally to all patients. But light therapy does not accompany pain and rarely
      shows any side effects. Therefore it is thought to be an alternative for patients
      who reject injection or patients who are not indicated for nerve block because of
      patients' conditions such as bleeding tendency.

PMID- 16984009
TI  - [Equipment for epiduroscopy and its clinical applications].
AB  - Equipments for epiduroscopy consist of an epidural endoscope, video camera
      system, video screen, recording system and C arm X-ray system. Epidural endoscope
      with a diameter of 0.9 mm is inserted from the hiatus sacralis, and has been used
      clinically for the observation of epidural space of a lumbar vertebrae level
      since 1996. There are still some problems to be solved in the epiduroscope
      development, but its dramatic pain reduction effect has been recognized and it
      has been held as an attractive diagnostic tool.

PMID- 16984010
TI  - [Current status of portable disposable infusers].
AB  - Portable disposable infusers are widely used for treatment of various types of
      pain including postoperative pain and cancer pain, because they are simple to
      use, of lightweight, and inexpensive. In Japan, nine series of infusers are
      available from eight manufacturers. Volumes and flow rates of various infusers
      used for pain therapy widely vary from 40 to 500 ml and from 0.5 to 15 ml x hr(
      1), respectively. Several infusers have flow selectors and/or patient-controlled
      analgesia circuits. Such a wide variety enables us to select optimal infusers for
      individual patients and thus to offer adequate pain control to those patients
      suffering from severe pain.

PMID- 16984011
TI  - [Electrical infusion pump for patient-controlled analgesia].
AB  - Electrical infusion pumps (pump) were featured with the focus on patient
      controlled analgesia (PCA). The specification and functional aspects of four
      types of PCA pumps were briefly summarized and listed in two tables. The clinical
      application of these PCA pumps should benefit both patients and medical staffs.
      For the successful introduction of PCA pumps into clinical practice, a medical
      team must be organized, where not only anesthesiologists but also nurses,
      pharmacists, medical electronic engineers and surgeons are expected to
      participate.

PMID- 16984012
TI  - [Neuromuscular blocking effects of Org 9426 (rocuronium bromide); a comparative
      study with vecuronium bromide in Japanese patients].
AB  - BACKGROUND: Efficacy and safety of Org 9426 were compared with those of
      vecuronium bromide in Japanese patients. METHODS: We studied 88 Japanese patients
      undergoing surgery requiring general anesthesia. Patients were allocated randomly
      to receive intubation dose of 0.6 mg x kg(-1), 0.9 mg x kg(-1) of Org 9426 or
      0.1mg x kg(-1) of vecuronium. Following an intubation dose, patients received
      maintenance doses of 0.1, 0.15 or 0.2 mg x kg(-1) of Org 9426 or 0.025 mg x kg(
      1) of vecuronium. The neuromuscular block was monitored with acceleromyography
      using TOF stimuli. Sevoflurane was administered to all treatment groups after
      intubation. RESULTS: The onset times of the 0.6 and 0.9 mg x kg(-1) of Org 9426
      groups were 84.6 and 77.1 sec respectively, which showed statistical difference
      between the onset time of 0.1 mg x kg(-1) of vecuronium, 125.7 sec. The
      intubation condition was similar among three treatment groups. The clinical
      durations of 0.6 and 0.9 mg x kg(-1) of Org 9426 and 0.1 mg x kg(-1) of
      vecuronium were 53.4, 73.4 and 59.9 min, respectively. Clinical duration and
      spontaneous recovery time of maintenance dose of 0.15 mg x kg(-1) of Org 9426
      were similar to those of 0.025 mg x kg(-1) of vecuronium. CONCLUSIONS: Org 9426
      showed more rapid onset time than that of vecuronium and similar clinical
      duration and recovery times to those of vecuronium in Japanese patients.

PMID- 16984013
TI  - [Study of analgestic efficacy of ropivacaine-fentanyl patient-controlled epidural
      analgesia after upper abdominal gynecological surgery].
AB  - BACKGROUND: Most of the patients who undergo radical or subradical hysterectomy
      with paraaortic lymphadenectomy suffer from postoperative pain for upper
      abdominal incision. They also complain of postoperative nausea and vomiting
      (PONV) frequently, which are increased by opioids. METHODS: Reducing total
      fentanyl dose to 0.6 mg, frequency of moving pain complaints increased gradually.
      Therefore, we introduced patient-controlled epidural analgesia (PCEA) for
      suppressing pain on moving. We investigated analgestic efficacy of 0.2%
      ropivacaine-fentanyl PCEA in twelve patients undergoing upper abdominal
      gynecological surgery. Postoperative analgesic effects were evaluated by visual
      analogue scale (VAS) at rest and on moving, times of bolus infusion, side
      effects, and degrees of satisfication by patient's self-assessments. Continuous
      epidural infusion of 0.6 mg fentanyl in 288 ml 0.2% ropivacaine was started at a
      rate of 4 ml x hr(-1) with a bolus dose of 2 ml. RESULTS: VAS was maintained
      below 20 mm at rest but was elevated to the maximum of 45 mm on moving with few
      bolus requests. Ninty-two percents of the patients answered satisfied but fifty
      percents of them had PONV. CONCLUSIONS: We conclude that ropivacaine-fentanyl
      PCEA is effective after upper abdominal gynecological surgery, and we can
      decrease the dose of fentanyl by explaining PCEA system more effectively to the
      patients for suppressing the pain on moving and PONV.

PMID- 16984014
TI  - [Preliminary report: observation by video laryngoscope of glottal narrowing due
      to cricoid pressure].
AB  - BACKGROUND: When the applied cricoid pressure is too strong, or the place or
      direction of the pressure application is not appropriate, glottal closure may
      occur, but its details are unclear. METHODS: We evaluated possible changes in the
      size of the rima glottides due to backward pressure on the cricoid cartilage or
      backward pressure or backward, upward, and rightward pressure (BURP) on the
      thyroid cartilage using a video laryngoscope (Fine View' Laryngoscope, Tray
      Medical, Tokyo) in 6 adult males and 6 females with Cormack and Lehane grade 1.
      RESULTS: The right-to-left distance of the rima glottides was 5.1 +/- 1.2 mm
      without pressure application but was reduced to 3.8 +/- 1.7, 3.5 +/- 1.8, 2.8 +/-
      1.9, 2.4 +/- 1.8, and 2.6 +/- 1.2 mm by 20 N and 30 N backward pressure on the
      cricoid cartilage and 20 N and 30 N backward pressure and BURP on the thyroid
      cartilage, respectively. Compared with the absence of pressure application, 20 N
      and 30 N backward pressure and BURP on the thyroid cartilage significantly
      reduced it. It was reduced to 1 mm by 30 N backward cricoid pressure in 1 patient
      while glottal closure occurred due to 30 backward thyroid pressure in 1 patient.
      CONCLUSIONS: The right-to-left distance of the rima glottides was significantly
      reduced by backward pressure or BURP on the thyroid cartilage, and was also
      markedly reduced by cricoid pressure in 1 of the 12 patients.

PMID- 16984015
TI  - [Perioperative management of abdominal operation in three patients with pulmonary
      emphysema associated with pulmonary hypertension].
AB  - Anesthesia for abdominal operation in patients with emphysema is accompanied with
      a high risk of respiratory insufficiency requiring postoperative artificial
      ventilation. Furthermore, in patients whose pulmonary emphysema progresses and
      leads to pulmonary hypertension, there is the risk of developing right heart
      failure with postoperative respiratory insufficiency. Because perioperative
      circulatory drifting is massive in abdominal operation, they develop right heart
      failure easily during the postoperative refilling phase. Therefore, it is
      important to avoid right heart failure during the postoperative period in these
      patients. We estimate pulmonary artery pressure using echocardiography at bedside
      and give dopamine for diuresis during the postoperative period. We succeeded in
      perioperative management of abdominal operation in three patients with pulmonary
      emphysema associated with pulmonary hypertension.

PMID- 16984016
TI  - [Effect of landiolol on heart rate control of atrial fibrillation in a patient
      with sick sinus syndrome under ventricular pacing].
AB  - A 62-year-old man with an ventricular pacemaker for sick sinus syndrome received
      right shoulder arthroplasty. During the intraoperative discrepancy between heart
      rate and pulse rate, continuous infusion of low dose landiolol was useful to
      control his heart rate of atrial fibrillation.

PMID- 16984017
TI  - [Assessment of sublingual PCO2 during selective cerebral perfusion].
AB  - We monitored sublingual tissue PCO2 (PSLCO2) continuously with an ISFET (ion
      sensitive field effect transistor) based PCO2 sensor during and after surgical
      treatment for descending aortic aneurysm. Using femoro-femoral bypass and a
      beating heart technique, distal end of aneurysm was clamped and then selective
      cerebral perfusion was performed into the left subclavian and left common carotid
      arteries. Aneurysmectomy and reconstructive surgery were carried out with
      proximal end of the left common carotid artery being clamped. Upon starting
      selective cerebral perfusion, PSLCO2 increased abnormally. PSLCO2 increased from
      38 mmHg just after induction of anesthesia to the maximum value of 87 mmHg during
      selective cerebral perfusion. Three hours after arriving in the intensive care
      unit, the patient developed convulsion and anisocoria and the computed tomography
      showed cerebral infraction. Since the blood flow to the tongue is fed through the
      internal and external carotid arteries, the increase in PSLCO2 is supposed to be
      caused by the decrease of blood flow to the tongue during selective cerebral
      perfusion. The monitoring of PSLCO2 may be a useful method to estimate the brain
      blood flow during selective cerebral perfusion.

PMID- 16984018
TI  - [Unintentional total spinal anesthesia during cervical epidural block with
      ropivacaine].
AB  - We present a case of unintentional total spinal anesthesia, which occurred during
      cervical epidural block. A 34-year-old man with complex regional pain syndrome of
      the right upper arm was treated with epidural block at C7-T1 interspace.
      Immediately after test-dose injection of ropivacaine 1.5 ml, he complained of
      paresthesia of his upper extremities. He developed difficulty talking and
      breathing. Subsequently he showed a complete paralysis with the loss of
      consciousness, respiratory arrest, and bilateral midriasis. Mandatory ventilation
      was started and endotracheal tube was placed. Eighty minutes after the injection
      of ropivacaine, he recovered consciousness and spontaneous respiration resumed.
      Checking adequate ventilation, his trachea was extubated. Neurological
      dysfunction was not seen thereafter. Although test-dose injection is recommended
      especially in high-risk patients and case of difficulty of epidural space
      identification, it does not fully prevent complications. For cervical epidural
      block, local anesthetics should either be given at small doses or not be given as
      long as a possibility of spinal injection is remaining.

PMID- 16984019
TI  - [Hepatic infarction following prolonged prone position].
AB  - A 61-year-old woman with chronic renal failure was scheduled for posterior spinal
      fusion. The duration of surgery was over ten hours and the patient was placed on
      prone position almost whole period of surgery. Although the surgery was finished
      without any obvious complications, laboratory examinations revealed marked liver
      dysfunction the day after the surgery. On the third postoperative day, computed
      tomography examination strongly suggested the liver infarction. Liver infarction
      has been considered as a rare complication because of two kinds of blood streams,
      the hepatic artery and the portal vein, but we should suspect the liver
      dysfunction from ischemia after the surgery of prolonged prone position.

PMID- 16984020
TI  - [Lymphangioleiomyomatosis: a case report].
AB  - We report anesthetic management of a patient with lymphangioleiomyomatosis. A 41
      year-old woman underwent lung biopsy under video-assisted thoracoscopic surgery
      to confirm the presence of lymphangioleiomyomatosis. She had hypoxemia due to
      obstructive lung disorder. Anesthesia was maintained with epidural block and
      general anesthesia with sevoflurane. During the operation, there were repeated
      episodes of hypoxemia, which required manual ventilation of the independent lung.
      After the operation, the tracheal tube was replaced with a laryngeal mask airway
      to minimize the risk of pneumothorax. There was no postoperative anesthesia
      related complication.

PMID- 16984021
TI  - [Labor management using epidural anesthesia in a gravida patient with high spinal
      injury].
AB  - Since autonomic hyperreflexia (AH) is a serious complication during labor in a
      gravida with spinal cord injury, anesthetic measures should be taken for the
      suppression of AH even in a sensory-loss condition. Several reports have
      described various methods for the suppression of AH, in which epidural anesthesia
      has been advocated as a useful means for the prevention or amelioration of AH.
      However, it is difficult to evaluate the efficacy of epidural anesthesia due to
      the lack of sensory and motor functions. We report a primipara who had spinal
      cord injury below the T 3 level at the age of 17 due to a traffic accident and
      underwent successful vaginal delivery twice under epidural anesthesia at the ages
      of 30 and 32. For the first delivery, we placed two epidural catheters. We
      controlled the rate and the content of epidural infusion through the two
      different injection sites so as to meet delivery process. For the second delivery
      we did epidural anesthesia in the same way. Tubal-ligation was also performed
      under epidural anesthesia after the second delivery. No major obstetric
      complication including AH occurred in either of delivery. The woman with high
      spinal injury could have two healthy children without major complications during
      labor by the cooperation of gynecologists and anesthesiologists.

PMID- 16984022
TI  - [Cardiac failure in a child during anesthetic induction with sevoflurane].
AB  - A five-year-old boy with recurring tonsillitis and sleep apnea was admitted for
      tonsillectomy and tympanic membrane tubing. He presented with a history of
      bronchial asthma and hereditary spherocytosis without obvious cardiac failure
      symptoms. Anesthetic agents for induction included nitrous oxide, oxygen, and
      sevoflurane. Because oxygen saturation decreased immediately to 90%, tracheal
      intubation was performed. The patient began to wheeze. Sevoflurane concentration
      was increased but cardiac murmur (gallop), cold limbs and jugular vein distension
      were noted. Acute cardiac failure was diagnosed following a chest X-ray and
      cardiac echo showing an enlarged heart, CTR of 80%, left ventricular dilation,
      and contractile failure. Tympanic membrane tubing only was performed. Sevoflurane
      was discontinued and the patient was treated for the cardiac failure under an ICU
      oxygen tent. The patient was discharged when his general condition improved. He
      showed elevated levels of viral antibodies, suggesting myocarditis. Later he was
      treated for dilating cardiomyopathy before undergoing a heart transplant.

PMID- 16984023
TI  - [MR studies of perivascular spaces with main emphasis on space-occupying
      lesions].

PMID- 16984025
TI  - [Only used unilateral transnasal approach applied endoscopic sinus surgery for
      pituitary adenomas].
AB  - Endoscope-assisted transnasal approach (TNA) for pituitary adenoma is a new
      alternative for Hardy's surgery (TSS). We performed TNA using only an endoscope
      through unilateral nostril. In our approach to sphenoid sinus, we apply method of
      endoscopic sinus surgery (ESS-TNA). We enter the sphenoid sinus directly through
      the natural ostium and do not brake the nasal septum nor vomer bone. Since
      September 2004 we had operated on 12 patients by endoscopic TNA. Six were non
      functioning adenomas, and 6 were functioning adenomas. We are first to open the
      ethomoid sinus to make the space for middle concha to be displaced laterally.
      Secondary, we widen the natural ostium of the sphenoid sinus, retracting the
      middle concha laterally. The results were compared with those in 10 cases by TSS
      operated in our institute. Adenoma removal more than 80% was achieved in 58% by
      endoscopic TNA whereas in 50% by TSS. We had no case with postsurgical infection.
      Transient DI occurred in 4 cases and 1 case showed permanent. CSF rhinorrhea was
      seen in the case having small empty sellae in front of adenoma. For this case, we
      packed the fat tissue at the floor of the sella with endoscope under local
      anesthesia to close the fistula. Three cases that had hemianopsia before surgery
      showed the recovery postoperatively. In 6 functional adenoma, postoperative
      endocrinological examinations showed normalization in 3 cases and improvements in
      3 cases. Postsurgical hospitalization days were 11.4 by endoscopic TNA whereas
      15.4 by TSS. Our method showed same or better results than TSS in the removal
      rate and complication rate whereas the postoperative duration of nasal packing
      and hospitalization days were shorter than TSS.

PMID- 16984024
TI  - [Cranial surgery without shaving: practice and results in our hospital].
AB  - Hair removal or shaving, even if partial, increases mental anguish of patients,
      especially in female. Several reports demonstrating successful cranial surgery
      without hair removal led us to start cranial surgery with completely preserving
      hair. The purpose of this study was to demonstrate our methods and tips of
      cranial surgery without hair removal and to evaluate the rate of postoperative
      infection in these patients. We performed 82 procedures without shaving,
      including craniotomy for brain tumors, trauma, intracranial aneurysms and so on
      (n = 70), ventriculo-peritoneal shunt placement (n = 5), and other miscellaneous
      procedures (n = 7). All the patients were highly satisfied with the cosmetic
      results keeping their hair. We observed 5 patients whose wounds took relatively
      long time to be cured (6.1%), and 2 patients whose wounds were infected (2.4%).
      All infections were superficial and cured by the application of antibiotic
      ointment. There was no significant difference between the rate of wound
      complication in patients whose heads were shaven (5/82) and the rate in those
      whose head were not shaven (7/82). So we suggest that neurosurgery without
      shaving is safe, and does not increase the risk of severe wound infection. In
      addition, it helps patients to look normal and to start their routine earlier.

PMID- 16984026
TI  - [Motor cortex stimulation for post-stroke pain using neuronavigation and evoked
      potentials: report of 3 cases].
AB  - Although motor cortex stimulation (MCS) has been accepted as an effective
      therapeutic option for central pain, the efficacy of MCS widely varies among
      previous reports. In this report, we describe our recent trial for successful MCS
      in 3 patients with central pain due to cerebral stroke. Medical treatments were
      transiently effective, but gradually became ineffective in all of the cases.
      During surgery, the appropriate cortical target was determined by using
      neuronavigation, somatosensory evoked potential (SEP), and motor evoked potential
      (MEP). A flat, four-plate electrode was positioned on the dura mater parallel to
      the motor cortex. After surgery, pain almost resolved in 2 of 3 patients and
      markedly improved in another. The pain relief depended on their motor function.
      These findings strongly suggest that both patient selection and intraoperative
      monitoring for targeting the motor cortex are quite important for successful MCS,
      although further studies were essential.

PMID- 16984027
TI  - [A case of cerebral arteriovenous malformation revealing repeated intranidal
      hemorrhage accompanying neovascularization after stereotactic radiosurgery].
AB  - We report a patient with cerebral arteriovenous malformation (AVM) revealing
      growing mass lesion after stereotactic radiosurgery. This 12-year-old female
      presented headache. CT scan showed hematoma at the head of the right caudate
      nucleus and angiography showed AVM at the site. LINAC-based stereotactic
      radiosurgery was performed with the patient. Twenty-three months after the
      radiosurgery the patient complained headache and CT scan showed hematoma again at
      the same site, although angiography did not show AVM. Thirty-five months after
      the radiosurgery mass lesion with enhancement effect was observed at the site and
      the mass lesion grew gradually thereafter. Thirty-nine months after the
      radiosurgery the mass lesion was evacuated. Histological examination revealed
      fibrotic core and surrounding neovascularized area with hemorrhage. The histology
      shows a new etiology of growing mass lesion after radiosurgery for AVM.

PMID- 16984028
TI  - [Cerebrospinal fluid leak due to inner ear malformations].
AB  - A case of inner ear anomalies associated with recurrent meningitis found in a 66
      year-old female is reported. The patient had had 2 episodes of meningitis in the
      previous one year period. Multidetector-row CT of the temporal bone and three
      demensional fast imaging employing steady-state acquisition MRI revealed
      dysplasia of the bony labyrinth and enlarged fundus of the internal auditory
      canal (IAC). During surgical treatment, we confirmed the cerebrospinal fluid
      (CSF) leakage through a bony defect in the stapedial footplate. The inner ear was
      obliterated and contained small pieces of temporal fascia. A meningitis or CSF
      leakage due to inner ear malformation is extreamly rear condition for
      neurosurgeon. Though we always have to take it into condideration as a cause of
      CSF leakage.

PMID- 16984029
TI  - [Superior sagittal sinus thrombosis suffered as a complication of ulcerative
      colitis: case report].
AB  - A case of superior sagittal sinus thrombosis which was complicated with
      ulcerative colitis is reported. A 16-year-old male patient had a 2-year history
      of ulcerative colitis. He was admitted to our hospital complaining of abdominal
      pain, bloody bowel discharge and appetite loss, and was then treated
      conservatively. Two days after admission, he demonstrated generalized convulsions
      which were followed by right hemiplegia. MRI showed a low intensity lesion on T1
      and an irregular high intensity in the subcortical area of the left frontal lobe
      on T2 and T2 FLAIR-weighted images. The MRI findings resembled either invasive
      brain tumor or local inflammation. Cerebral angiography appeared to demonstrate
      complete obstruction of the superior sagittal sinus with congestion of venous
      flow in the cortical veins. Ulcerative colitis has been reported to show
      hypercoagulation, leading to deep vein thrombosis within the body which sometimes
      causes pulmonary infarction; however, occurrence of venous thrombosis in the
      intracranial veins and sinus is rare. This report underscores the fact that
      cerebral venous thrombosis should be suspected in the case of patients with
      ulceritive colitis who suffer sudden onset of neurological deficits.

PMID- 16984030
TI  - [A case of atretic cephalocele].
AB  - We report a case of atreric cephalocele. A 13-year-old boy who was
      developmentally normal was admitted to our hospital, complaining of scalp mass
      located at the midparietal region. He was noticed to have had it since his birth.
      Physical examination revealed 2.5 x 2.5cm, round, skin-covered midline subscalp
      mass with a hairless top. Bone 3D-CT showed bone defect at the base of the mass.
      MRI and MR venography showed the embryonic positioning of the straight sinus. He
      was treated with surgical excision of the mass, and fibrous tract extending
      intracranially at the base of the lesion was identified. Pathologic examination
      showed it to be meningocele.

PMID- 16984031
TI  - [A case of brain metastasis from gastric cancer involving bilateral middle
      cerebellar peduncles].
AB  - A case with brain metastasis involving bilateral middle cerebellar peduncles
      (bMCP) was reported. A 71-year-old male with gastric cancer was treated for
      multiple brain metastasis by gamma knife radiosurgery (GKR) in September, 2004.
      Two months after the initial GKR, MRI showed asymmetrical enhanced lesions
      involving bMCP. A few months later, MRI revealed an expansional infiltration of
      bMCP lesions. The patient had presented with headache loss of appetite,
      cerebellar ataxia, diplopia and slight dysmetria. PET showed 2-deoxy-2- [18F]
      fluoro-D-glucose (FDG) uptake of the bMCP lesions. The lesions were diagnosed as
      brain metastasis of gastric cancer. The patient underwent his second GKR
      (marginal dose : 19Gy, maximum dose 38Gy) MRI revealed the disappearance of the
      tumors 3 months after the second GKR. One year later, the patient showed no
      evidence of recurrence. For the last time, our case was diagnosed as brain
      metastasis from gastric cancer without meningeal carcinomatosis. It was suggested
      that FDG-PET can provide additional information about the lesion of bMCP. GKR may
      be useful to treat the tumor in bMCP.

PMID- 16984032
TI  - [Simultaneous determination of pesticides in agricultural products by LC/MS/MS
      using clean-up with ultrafiltration].
AB  - A method for simultaneous determination of multiple pesticide residues in
      agricultural products was developed by using a pretreatment with ultrafiltration,
      followed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The
      pretreatment process (extraction of pesticides from agricultural products with
      methanol, dilution of the extract with water, and ultrafiltration) gave
      recoveries in the range of 50-150% for 63 of 83 pesticides spiked at 0.25 microg/
      g into 6 agricultural products. The detection limits of pesticides by LC/MS/MS
      were below 0.0005-0.05 micro/g. This method is useful for screening purposes and
      for multiresidue analysis of pesticides in agricultural products. Pesticide
      residues in 50 domestic crops were investigated by this method, and residues of
      14 pesticides were detected in 30 crops.

PMID- 16984033
TI  - Detection method for genetically modified papaya using duplex PCR.
AB  - A simple and rapid method for the identification of genetically modified (GM)
      papaya, derived from Line 55-1, was developed by modifying the Japanese official
      PCR method. Genomic DNA was directly extracted from the fresh fruit without the
      lyophilization step, using a commercial silica-based kit. To develop a duplex PCR
      method which simultaneously detects the GM papaya-specific gene and the intrinsic
      papain gene, the papain 2-5'/3' (amplicon size; 184 bp) primer pair for the
      detection of the papain gene was newly designed within the region of the products
      (211 bp) amplified using the papain 1-5'/-3' primer pair adopted in the Japanese
      official PCR method. To detect the GM papaya-specific gene, the primer pair Nos C
      5'/CaM N-3' described in the Japanese official method was used. The DNA sequences
      of the GM papaya gene and the intrinsic papain gene were co-amplified using the
      PCR method in a single tube. The developed duplex PCR method allows the
      simultaneous detection of the products by means of agarose gel electrophoresis or
      microchip electrophoresis. The proposed method for GM papaya identification is
      simple and rapid.

PMID- 16984035
TI  - [Estimation of daily intake of PCDDs, PCDFs and Co-PCBs from baby foods].
AB  - A study of the dietary intake of dioxins, consisting of polychlorinated dibenzo-p
      dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and coplanar
      polychlorinated biphenyls (Co-PCBs) through baby foods in the metropolitan Tokyo
      area was carried out. The samples were homemade baby foods prepared by the total
      diet-market basket method and baby foods (mainly commercial items) prepared by
      the duplicate portion method. The daily intake of dioxins per kg of body weight
      from baby foods in each weaning stage for the case of half intake of homemade
      baby foods and the other half of mainly commercial items was 0.32 pg TEQ/kg/day
      in the early stage, 0.45 pg TEQ/kg/day in the intermediate stage, 0.58 pg
      TEQ/kg/day in the late stage and 1.25 pg TEQ/kg/day in the completed stage. While
      the daily intakes increase with the weaning progress, they were less than the
      tolerable daily intake (TDI) of 4 pg TEQ/kg/day for dioxins established in Japan.
      Dioxins were mainly taken through formula milk in early stage of weaning period,
      but then were taken through protein-based foods in the subsequent weaning stage.

PMID- 16984034
TI  - Novel method for estimating viable Salmonella cell counts using real-time PCR.
AB  - A novel method for estimating viable Salmonella Enteritidis cell counts with 5'
      nuclease real-time PCR was developed in this study. Our method was based on the
      increase kinetics of the target DNA region (invA) of the microorganism growing in
      a food/clinical sample in a culture medium during incubation. The index of
      increase in the target DNA region studied here was threshold cycle, CT. A test
      Salmonella strain was grown in buffered peptone water at the optimal temperature
      (39 degrees C). As Salmonella cells were grown, the value of CT decreased with
      time, generating a downward sigmoidal curve. The slope of the curve was constant
      at various initial cell concentrations. With higher initial cell concentration,
      the CT value evaluated from the slope at a given time was lower. With this
      relationship, a novel method for estimating the initial viable cell concentration
      of a sample was developed. Dead Salmonella cells or bacteria other than the
      target cell caused deviation in the CT curve. Incubation in a selective media
      suppressed the deviation caused by other bacterial cells. We think that this
      method could be applied to many other microorganisms cultivable in a suitable
      medium.

PMID- 16984036
TI  - [Study on pyrogen in natural and cultivated edible mushrooms].
AB  - We examined endotoxin and pyrogen contents in several kinds of natural and
      cultivated edible mushrooms, as well as some cultivated vegetables. According to
      the Japanese Pharmacopoeia, 14th Ed., two types of endotoxin (gel-clot Limulus
      amebocyte lysate) test and the pyrogen test were performed using natural edible
      mushrooms collected in Aichi Prefecture and cultivated mushrooms and vegetables
      purchased at a market. The endotoxin contents of natural mushrooms were
      apparently higher than those of cultivated mushrooms or vegetables. The endotoxin
      contents in the cultivated mushrooms were slightly higher than those in the
      vegetables. Similar results were obtained in the pyrogen test.

PMID- 16984037
TI  - [Analysis of constituents in urushi wax, a natural food additive].
AB  - Urushi wax is a natural gum base used as a food additive. In order to evaluate
      the quality of urushi wax as a food additive and to obtain information useful for
      setting official standards, we investigated the constituents and their
      concentrations in urushi wax, using the same sample as scheduled for toxicity
      testing. After methanolysis of urushi wax, the composition of fatty acids was
      analyzed by GC/MS. The results indicated that the main fatty acids were palmitic
      acid, oleic acid and stearic acid. LC/MS analysis of urushi wax provided
      molecular-related ions of the main constituents. The main constituents were
      identified as triglycerides, namely glyceryl tripalmitate (30.7%), glyceryl
      dipalmitate monooleate (21.2%), glyceryl dioleate monopalmitate (2.1%), glyceryl
      monooleate monopalmitate monostearate (2.6%), glyceryl dipalmitate monostearate
      (5.6%), glyceryl distearate monopalmitate (1.4%). Glyceryl dipalmitate monooleate
      isomers differing in the binding sites of each constituent fatty acid could be
      separately determined by LC/MS/MS.

PMID- 16984038
TI  - [Analytical method for methoprene in foods using HPLC].
AB  - We studied the determination of methoprene in foods by high-performance liquid
      chromatography (HPLC). The sample was extracted with acetonitrile and the extract
      was salted out by adding sodium chloride, allowing the acetonitrile layer to
      separate. The acetonitrile solution was washed with hexane saturated with
      acetonitrile, cleaned up on a Florisil column and determined by HPLC. The
      recovery of methoprene from spiked samples was 74.6-82.8%. In an evaluation of
      this method by 6 analytical laboratories, mean recoveries from spiked samples
      ranged from 79.4% to 84.6%. Repeatability relative standard deviation values were
      2.3-8.8% and reproducibility relative standard deviation values were 8.8-23.6%.
      The detection limits were 0.001-0.02 microg/g and below the detection limit of
      the Notified Analytical Method.

PMID- 16984039
TI  - Characteristic long-chain fatty acid of Pleurocybella porrigens.
AB  - As part of an investigation on the chemical constituents and contaminants of the
      basidiomycete Pleurocybella porrigens (Japanese name: Sugihiratake), we analyzed
      the UV-detected constituents of this mushroom using HPLC. One of the major UV
      peaks detected was isolated and identified as a-eleostearic acid, a long-chain
      fatty acid with a conjugated triene moiety, based on the results of spectroscopic
      methods. alpha-Eleostearic acid was concluded to be a characteristic fatty acid
      of P. porrigens, because it was not detected in eight other edible mushrooms
      examined. Free long-chain fatty acids in P. porrigens and other edible mushrooms
      were analyzed by HPLC after derivatization with acidic 2-nitrophenylhydrazine
      hydrochloride. Oleic acid was the main fatty acid in P. porrigens, and saturated
      long-chain fatty acids such as linoleic acid, palmitic acid, and stearic acid,
      together with a-eleostearic acid, were also detected.

PMID- 16984040
TI  - Levels of dioxins in rice, wheat, soybean, and adzuki bean cultivated in 1999 to
      2002 in Japan and estimation of their intake.
AB  - A total of 369 samples of rice (n = 311), wheat (n = 10), soybean (n = 44), and
      adzuki bean (n = 4) collected from various locations in Japan between 1999 and
      2002 were 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 toxic equivalent quantity
      (TEQ) values of soybean samples collected from near-source areas were
      significantly higher (p < 0.05) than those from general areas. A significant
      difference of TEQs among sampling years in rice in general areas was also found.
      However, the differences could not be explained by the presence or absence of
      incineration plants in the area surrounding the sampling point or by a temporal
      decrease of air pollution. The TEQs of the crops varied widely, but the median
      value of each crop was quite low, at 0.000021, 0.00013, 0.0000095, and 0.00016 pg
      TEQ/g wet wt. in rice, wheat, soybean and adzuki bean, respectively. On the basis
      of these survey results, the daily intake of PCDD/Fs and coplanar PCBs from rice,
      wheat, soybean, and adzuki bean was calculated. The daily intakes from these
      crops were estimated to be 0.0056 pg-TEQ/kg B.W./day on the assumption that "not
      detected" (ND) could be taken as zero, ND = 0, and 0.18 pg-TEQ/kg B.W./day if ND
      is put equal to 1/2 LOD (half the limit of detection). In comparison with the
      tolerable daily intake set in Japan for PCDD/Fs and coplanar PCBs (4 pg-TEQ/kg
      B.W./day), it was considered that the levels of contamination by PCDD/Fs and
      coplanar PCBs in these crops cultivated in the environment of Japan do not
      present a problem.

PMID- 16984041
TI  - [Example of examination of allergic substances (egg, milk) in commercial foods].
AB  - Allergic substances (eggs, milk) in commercial foods were measured by means of
      the notified ELISA methods using FASTKIT ELISA kit (N kit) and "Tokuteigenzairyo
      sokutei kit" (M kit). Some samples were also analyzed with the notified western
      blot method using "Tokuteigenzairyo western blot kit". In the methods for
      detection of eggs, proteins of fish egg and chicken muscle were examined using
      the ELISA and Western blotting methods to check for cross-reaction. Sujiko was
      false positive with the M kit. Difficulties were also encountered in the notified
      ELISA and Western blotting methods with raw chicken. In foods labeled as
      containing eggs, it was difficult to detected in the heart-processed food using
      both notified methods. In the method for detection of milk, foods containing
      thickening polysaccharides, showed cross-reaction with the N kit. However, this
      cross-reaction was eliminated when an improved N kit was used. Foods labeled as
      containing milk did not present any difficulty.

PMID- 16984042
TI  - [Survey of epoxidized soybean oil in cap sealing for bottled foods].
AB  - Epoxidized soybean oil (ESBO) was surveyed in the 103 samples of cap sealing for
      bottled foods on the Japanese market. Most of the sealings were made of polyvinyl
      chloride, while a few were made of polyethylene or acrylic resin. All the
      sealings contained ESBO in the range of 0.006-42.4%. Sealings for baby food, jam,
      etc. contained higher levels of ESBO, though those for beverages contained lower
      levels. Sealings in lug caps and press-on twist caps contained higher levels of
      ESBO, though that in pilfer-proof caps contained lower levels. Some sealings in
      screw caps and lug caps also contained other plasticizers, for example, di-2
      ethylhexyl phthalate and diisononyl phthalate, and their ESBO contents were 1/10
      of those in sealings containing only ESBO. In this survey, ESBO was the most
      common plasticizer in cap sealing resin for bottled foods on the Japanese market.

PMID- 16984043
TI  - [Sanitation programs for oysters in Japan and many foreign countries].

PMID- 16984044
TI  - [ComBase: the international database for predictive microbiology].

PMID- 16984045
TI  - [Bacteria in viable but non-culturable state].

PMID- 16984046
TI  - [Results and issues in risk communication on "food safety risk assessment related
      to methylmercury in seafood"].

PMID- 16984047
TI  - [Necessity of food chain approach for safe food].

PMID- 16984048
TI  - [Good agricultural practice (GAP) for food safety].

PMID- 16984049
TI  - [Contamination with Campylobacter and Salmonella in chicken meat and its
      control].

PMID- 16984050
TI  - [Food allergy, labeling and risk communication].

PMID- 16984051
TI  - [Security for food safety and food safety management system (ISO 22000)].

PMID- 16984052
TI  - [Practical use and technical notice of LC/MS/MS for routine analysis of pesticide
      residues in agricultural products].

PMID- 16984053
TI  - Expanding the scientific basis of health technology assessment: a research agenda
      for the next decade.
AB  - OBJECTIVES: The complexity of health technology assessment (HTA) has increased,
      in part because of its evolution through three distinct phases: the machine, the
      clinical outcomes, and the delivery models. However, the theoretical foundation
      for the field remains underdeveloped. METHODS: It is high time for HTA to bring
      together aspects of conceptual and theoretical works from other fields to
      strengthen the foundation of HTA. RESULTS: Many challenges await the further
      development of HTA. They can be captured around three research themes: adapting
      HTA to an evolving analysis object; translating HTA results into policy,
      management, and practice decisions; and evaluating organizational models of HTA.
      CONCLUSIONS: Consolidating the scientific basis of HTA is essential if we are to
      succeed in increasing the relevance of HTA in some of the most challenging health
      related decisions that we will make as individuals and societies.

PMID- 16984054
TI  - Searching for and use of conference abstracts in health technology assessments:
      policy and practice.
AB  - OBJECTIVES: Current policy and practice regarding identification of and extent of
      use of data from conference abstracts in health technology assessment reviews
      (TARs) are examined. METHODS: The methods used were (i) survey of TAR groups to
      identify general policy and experience related to use of abstract data, and (ii)
      audit of TARs commissioned by the National Institute for Health and Clinical
      Excellence (NICE) and published between January 2000 and October 2004. RESULTS:
      Five of seven TAR groups reported a general policy that included searching for
      and including studies available as conference abstracts and presentations. A
      total of sixty-three published HTA reports for NICE were identified. Of these
      reports, thirty-eight identified at least one randomized controlled trial
      available as an abstract/presentation. Twenty-six (68 percent) of these thirty
      eight TARs included studies available as abstracts. CONCLUSIONS: There are
      variations in policy and practice across TAR groups regarding the searching for
      and inclusion of studies available as conference abstracts. There is a need for
      clarity and transparency for review teams regarding how abstract data are
      managed. If conference abstracts are to be included, reviewers need to allocate
      additional time for searching and managing data from these sources. Review teams
      should also be encouraged to state explicitly their search strategies for
      identifying conference abstracts, their methods for assessing these abstracts for
      inclusion and, where appropriate, how the data were used and their effect on the
      results.

PMID- 16984055
TI  - Case study of the comparison of data from conference abstracts and full-text
      articles in health technology assessment of rapidly evolving technologies: does
      it make a difference?
AB  - OBJECTIVES: The aim of this study was to examine (i) the consistency of reporting
      research findings presented in conference abstracts and presentations and
      subsequent full publications, (ii) the ability to judge methodological quality of
      trials from conference abstracts and presentations, and (iii) the effect of
      inclusion or exclusion of data from these sources on the pooled effect estimates
      in a meta-analysis. METHODS: This report is a case study of a selected health
      technology assessment review (TAR) of a rapidly evolving technology that had
      identified and included a meta-analysis of trial data from conference abstracts
      and presentations. RESULTS: The overall quality of reporting in abstracts and
      presentations was poor, especially in abstracts. There was incomplete or
      inconsistent reporting of data in the abstract/presentations. Most often
      inconsistencies were between conference slide presentations and data reported in
      published full-text articles. Sensitivity analyses indicated that using data only
      from published papers would not have altered the direction of any of the results
      when compared with those using published and abstract data. However, the
      statistical significance of three of ten results would have changed. If
      conference abstracts and presentations were excluded from the early analysis, the
      direction of effect and statistical significance would have changed in one
      result. The overall conclusions of the original analysis would not have been
      altered. CONCLUSIONS: There are inconsistencies in data presented as conference
      abstracts/presentations and those reported in subsequent published reports. These
      inconsistencies could impact the final assessment results. Data discrepancies
      identified across sources included in TARs should be highlighted and their impact
      assessed and discussed. Sensitivity analyses should be carried out with and
      without abstract/presentation data included in the analysis. Incomplete reporting
      in conference abstracts and presentations limits the ability of reviewers to
      assess confidently the methodological quality of trials.

PMID- 16984056
TI  - Doing mini-health technology assessments in hospitals: a new concept of decision
      support in health care?
AB  - OBJECTIVES: The purpose of this project was to evaluate local decision support
      tools used in the Danish hospital sector from a theoretical and an empirical
      point of view. METHODS: The use of local decision support was evaluated through
      questionnaires sent to all county health directors, all hospital managers, and
      all heads of clinical departments in cardiology, orthopedic surgery, and
      intensive care. In addition, respondents were asked to submit whatever decision
      support tools they were using (including mini-HTAs, other forms or checklists,
      and special procedures for decision making concerning new health technologies). A
      theoretical analysis of the decision support tools (decision theory) was
      performed as well as a comparison with the business case method used in private
      companies. Finally, the Danish mini-HTA was compared with foreign production and
      use of HTA and HTA-like assessments as local decision support. RESULTS: The
      response rate was high (87 percent, 94 percent, 85 percent, respectively). We
      collected sixty different forms (of which forty-nine were mini-HTAs) and twenty
      variants of written procedures. We found theoretical and empirical evidence that
      local involvement in the process of making the HTA could be important for the use
      of the results from the HTA and for the process of implementing the new
      technology. CONCLUSIONS: Doing mini-HTA in hospitals seems to balance the need
      for quality and depth with the limited time and resources for assessment.

PMID- 16984057
TI  - Technology assessment and knowledge brokering: the case of assisted reproduction
      in The Netherlands.
AB  - OBJECTIVES: Even when policy makers show interest and evidence-informed and
      convincing HTA studies are available, use of assessment products is not
      guaranteed. In this article, we report our experience with knowledge brokering to
      foster evidence-informed policy making on cost-effective treatment and
      reimbursement of assisted reproduction in The Netherlands. METHODS: From earlier
      work in the field of knowledge brokering, we foresaw the need for a deliberative
      strategy to manage the inherent tension between scientific rigor demanded by
      researchers and responsiveness to real-time needs demanded by policy makers.
      Therefore, we structured the process in three distinct steps: (i) agreement about
      the main messages from the research, (ii) analysis of the policy context and of
      the meaning of the main messages for the actors involved, and (iii) an
      invitational meeting to make recommendations for action. RESULTS: One of the
      recommendations that would require changes in ministerial policy was followed up
      instantly, whereas the other recommendation is still under debate. The Dutch
      Society of Obstetrics and Gynecology activated the revision of two guidelines.
      The patient organization uses the new scientific insights in informing members
      and the public. Closing the loop, The Netherlands Organisation for Health
      Research and Development (ZonMw) funded research to close knowledge gaps that
      became apparent in the process. CONCLUSIONS: Knowledge brokering is a promising
      approach to bring HTA into practice. We conclude that the methodologies to feed
      research results into the policy process are still in an incipient stage and need
      further development.

PMID- 16984058
TI  - Ethics and health technology assessment: handmaiden and/or critic?
AB  - OBJECTIVES: This study examines the content and role of ethical analysis in
      health technology assessment (HTA) and horizon scanning publications. It proposes
      that ethical analysis in HTA is of at least two different types: an ethics of HTA
      and an ethics in HTA. METHODS: I examine the critical differences between these
      approaches through the examples of the analysis of genetic screening for breast
      cancer and home blood glucose testing in diabetes. I then argue that, although
      both approaches subscribe to similar views concerning HTA and ethics, they use
      different theoretical and methodological traditions to interpret and explain
      them. RESULTS AND CONCLUSIONS: I conclude by suggesting that we need the
      interpretive insights of both these approaches, taken together, to explain why
      ethics has not been able yet to contribute fully to HTA and to demonstrate the
      scope and complexity of ethical work in this domain.

PMID- 16984059
TI  - Early home-supported discharge of stroke patients: a health technology
      assessment.
AB  - OBJECTIVES: A comprehensive and systematic assessment (HTA) of early home
      supported discharge by a multidisciplinary team that plans, coordinates, and
      delivers care at home (EHSD) was undertaken and the results were compared with
      that of conventional rehabilitation at stroke units. METHODS: A systematic
      literature search for randomized trials (RCTs) on "early supported discharge" was
      closed in April 2005. RCTs on EHSD without information on (i) death or
      institution at follow-up, (ii) change in Barthel Index, (iii) length of hospital
      stay, (iv) intensity of home rehabilitation, or (v) baseline data are excluded.
      Seven RCTs on EHSD with 1,108 patients followed 3-12 months after discharge are
      selected for statistical meta-analysis of outcomes. The costs are calculated as a
      function of the average number of home training sessions. Economic evaluation is
      organized as a test of dominance (both better outcomes and lower costs). RESULTS:
      The odds ratio (OR) for "Death or institution" is reduced significantly by EHSD:
      OR = .75 (confidence interval [CI], .46-.95), and number needed to treat (NNT) =
      14. Referrals to institution have OR = .45 (CI, .31-.96) and NNT = 20. The
      reduction of the rate of death is not significant. Length of stay is
      significantly reduced by 10 days (CI, 2.6-18 days). All outcomes have a
      nonsignificant positive covariance. The median number of home sessions is eleven,
      and the average cost per EHSD is 1,340 USD. The "action mechanism" and financial
      barriers to EHSD are discussed. CONCLUSIONS: EHSD is evidenced as a dominant
      health intervention. However, financial barriers between municipalities and
      health authorities have to be overcome. For qualitative reasons, a learning path
      of implementation is recommended where one stroke unit in a region initiates EHSD
      for dissemination of new experience to the other stroke units.

PMID- 16984060
TI  - Economics of tandem mass spectrometry screening of neonatal inherited disorders.
AB  - OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of
      neonatal screening for phenylketonuria (PKU) and medium-chain acyl-coA
      dehydrogenase (MCAD) deficiency using tandem mass spectrometry (tandem MS).
      METHODS: A systematic review of clinical efficacy evidence and cost-effectiveness
      modeling of screening in newborn infants within a UK National Health Service
      perspective was performed. Marginal costs, life-years gained, and cost
      effectiveness acceptability curves are presented. RESULTS: Substituting the use
      of tandem MS for existing technologies for the screening of PKU increases costs
      with no increase in health outcomes. However, the addition of screening for MCAD
      deficiency as part of a neonatal screening program for PKU using tandem MS, with
      an operational range of 50,000 to 60,000 specimens per system per year, would
      result in a mean incremental cost of -pound 17,298 (-pound 129,174, pound 66,434)
      for each cohort of 100,000 neonates screened. This cost saving is associated with
      a mean incremental gain of 57.3 (28.0, 91.4) life-years. CONCLUSIONS: Cost
      effectiveness analysis using economic modeling indicates that substituting the
      use of tandem MS for existing technologies for the screening of PKU alone is not
      economically justified. However, the addition of screening for MCAD deficiency as
      part of a neonatal screening program for PKU using tandem MS would be
      economically attractive.

PMID- 16984061
TI  - Genetic screening by DNA technology: a systematic review of health economic
      evidence.
AB  - OBJECTIVES: The Human Genome Project has led to a multitude of new potential
      screening targets on the level of human DNA. The aim of this systematic review is
      to critically summarize the evidence from health economic evaluations of genetic
      screening in the literature. METHODS: Based on an extensive explorative search,
      an appropriate algorithm for a systematic database search was developed. Twenty
      one health economic evaluations were identified and appraised using published
      quality criteria. RESULTS: Genetic screening for eight conditions has been found
      to be investigated by health economic evaluation: hereditary breast and ovarian
      cancer, familial adenomatous polyposis (FAP) colorectal cancer, hereditary
      nonpolyposis colorectal carcinoma (HNPCC), retinoblastoma, familial
      hypercholesterolemia, hereditary hemochromatosis, insulin-dependent diabetes
      mellitus, and cystic fibrosis. Results range from dominated to cost-saving.
      Population-wide genetic screening may be considered cost-effective with limited
      quality of evidence only for three conditions. The methodology of the studies was
      of varying quality. Cost-effectiveness was primarily influenced by mutation
      prevalence, genetic test costs, mortality risk, effectiveness of treatment, age
      at screening, and discount rate. CONCLUSIONS: Health economic evidence on genetic
      screening is limited: Only few conditions have properly been evaluated. Based on
      the existing evidence, healthcare decision makers should consider the
      introduction of selective genetic screening for FAP and HNPCC. As genetic test
      costs are declining, the existing evaluations may warrant updating. Especially in
      the case of hereditary hemochromatosis, genetic population screening may be about
      to turn from a dominated to a cost-effective or even cost-saving intervention.

PMID- 16984062
TI  - The economics of blood: gift of life or a commodity?
AB  - OBJECTIVES: To calculate the costs of blood collection, testing, storage, and
      transfusion in Greece. METHODS: Costing information was collected from two large
      public hospitals, in Athens and Crete, that also act as blood banks. Given that
      private health care accounts for 40 percent of total health spending, the same
      costs were also considered in a private setting by collecting key reagent cost
      data from a leading private hospital in Athens. Mainly direct costs were
      considered (advertising campaigns, personnel, storage and maintenance, reagent
      costs, transportation costs from blood bank to end-use hospitals, and cross
      matching and transfusion costs in receiving hospitals) and some indirect costs
      (opportunity cost of blood donorship). RESULTS: Captive donorship accounts for
      over 50 percent of the national blood supply. A unit of blood transfused would
      cost between Euro 294.83 and Euro 339.83 in public hospitals and could reach Euro
      413.93 in a private facility. This figure may be an underestimate, as it excludes
      opportunity costs of blood transfusion for patients and the healthcare system.
      CONCLUSIONS: Blood has a significant cost to the health system. Policy makers and
      practitioners should encourage its rational use, build on current policies to
      further improve collection and distribution, encourage further volunteer
      donorship in Greece, and also consider alternatives to blood where the
      possibility exists.

PMID- 16984063
TI  - Women's preferences for cervical cancer screening: a study using a discrete
      choice experiment.
AB  - OBJECTIVES: Recent policy recommendations for cervical screening include liquid
      based cytology. This new approach could improve laboratory throughput, reducing
      the waiting time for test results. New guidelines also standardize the interval
      for screening, with women aged 25-50 offered screening every 3 years and women
      aged 50-64 every 5 years. Quantitative evidence on the preferences of women for
      alternative screening programs is limited; this study, therefore, elicits such
      preferences. METHODS: A postal questionnaire using a discrete choice experiment
      was mailed to 2,000 women in the Tayside Health Board region of Scotland.
      RESULTS: A response rate of 44 percent from those women who had previously had a
      smear was achieved. Women had a significant positive preference for reductions in
      recall rates and waiting time for results. Women preferred more frequent
      screening, particularly those aged 50+. Expected reductions in the chance of
      recall from the conventional Pap smear to the new liquid-based cytology were
      associated with a willingness to pay of pound 41. Women aged 50+ would be willing
      to pay pound 42 to increase the frequency of screening from every 5 to every 3
      years. Service characteristics did not influence screening participation.
      CONCLUSIONS: Guidance to move to liquid-based cytology will meet women's
      preferences for fewer repeat cervical smears and should reduce waiting time for
      results. However, proposals to increase screening intervals for those aged 50+
      are inconsistent with the preferences for this age group. From a policy
      perspective, our study results suggest that the changes in attributes of the
      service such as unsatisfactory smear rates and frequency of screening, will
      improve service efficiency without affecting participation rates.

PMID- 16984064
TI  - Decision makers' and scientists' opinion about contingent valuation and choice
      experiments for measuring willingness to pay in health care: results from a
      survey in Germany.
AB  - OBJECTIVES: Assessment of willingness to pay (WTP) by contingent valuation (CV)
      and choice experiments (CE) is increasingly performed in economic evaluation of
      health care. However, the question of whether the methods for measuring WTP are
      acceptable to decision makers and scientists has remained largely unacknowledged.
      The aim of this study was to learn more about decision makers' and scientists'
      opinion concerning these methods. METHODS: An expert group developed a
      questionnaire consisting of key items that may influence the opinion about CV and
      CE according to the constructs "attitude toward behavior," "subjective norm," and
      "behavioral intention" as defined by the Theory of Reasoned Action by Ajzen and
      Fishbein. In a survey, seventy-seven decision makers representing key
      institutions in the German healthcare system and forty-two scientists in health
      economics completed the questionnaire. RESULTS: Scientists and decision makers in
      particular did not show a high intention to use methods for measuring WTP.
      Skepticism regarding precision of the methods and subjects' capability to imagine
      paying an amount of money for a certain health commodity were stated along with
      the assertion that the hypothetical decision-making scenario was rather a distant
      reality. Nevertheless, the majority of scientists and decision makers did not
      state rejection of the methods. CONCLUSIONS: Increasing the probability of using
      methods for measuring WTP in health care, the hypothetical scenarios should be
      made more realistic and payment vehicles should be used to help patients relate
      payment to a real health benefit. Moreover, an intensive discussion on the
      potential usefulness of CV/CE without excluding ethical concerns in comparison to
      existing alternatives has to be resumed.

PMID- 16984065
TI  - Economic evaluation of empirical antisecretory therapy versus Helicobacter pylori
      test for management of dyspepsia: a randomized trial in primary care.
AB  - OBJECTIVES: An economic evaluation was performed of empirical antisecretory
      therapy versus test for Helicobacter pylori in the management of dyspepsia
      patients presenting in primary care. METHODS: A randomized trial in 106 general
      practices in the County of Funen, Denmark, was designed to include prospective
      collection of clinical outcome measures and resource utilization data. Dyspepsia
      patients (n = 722) presenting in general practice with more than 2 weeks of
      epigastric pain or discomfort were managed according to one of three initial
      management strategies: (i) empirical antisecretory therapy, (ii) testing for
      Helicobacter pylori, or (iii) empirical antisecretory therapy, followed by
      Helicobacter pylori testing if symptoms improved. Cost-effectiveness and
      incremental cost-effectiveness ratios of the strategies were determined. RESULTS:
      The mean proportion of days without dyspeptic symptoms during the 1-year follow
      up was 0.59 in the group treated with empirical antisecretory therapy, 0.57 in
      the H. pylori test-and-eradicate group, and 0.53 in the combination group. After
      1 year, 23 percent, 26 percent, and 22 percent, respectively, were symptom-free.
      Applying the proportion of days without dyspeptic symptoms, the cost
      effectiveness for empirical treatment, H. pylori test and the combination were
      12,131 Danish kroner (DKK), 9,576 DKK, and 7,301 DKK, respectively. The
      incremental cost-effectiveness going from the combination strategy to empirical
      antisecretory treatment or H. pylori test alone was 54,783 DKK and 39,700 DKK per
      additional proportion of days without dyspeptic symptoms. CONCLUSIONS: Empirical
      antisecretory therapy confers a small insignificant benefit but costs more than
      strategies based on test for H. pylori and is probably not a cost-effective
      strategy for the management of dyspepsia in primary care.

PMID- 16984066
TI  - Measuring quality of life: the development and initial validation of the patient
      reported erectile function assessment instrument.
AB  - OBJECTIVES: Erectile dysfunction (ED) is a complex condition, which is variously
      influenced by physical, emotional, societal, and relationship factors. ED has
      serious implications for the quality of life (QoL) enjoyed by an affected male
      and his partner. It is very important, therefore, to understand the impact of ED
      on the QoL of those affected by it. Our objective was to determine if the eight
      question Patient Reported Erectile Function Assessment (PREFA) could act as an
      independent, comprehensive disease-specific instrument in the assessment of QoL
      as it is impacted by ED. METHODS: During the development and validation of the
      Erectile Function-Visual Analog Scale (EF-VAS) (14), a new ED-specific preference
      based instrument, a series of questions were included at the beginning of the
      assessment that would act as a way to encourage respondents to focus on their own
      experience with ED. Upon analysis of the EF-VAS data, it became apparent that the
      eight-question "warm up" section might act as a stand-alone assessment.
      Accordingly, the eight questions were named PREFA, and a validation analysis was
      undertaken to determine their consistency, feasibility, reliability, validity,
      and responsiveness. RESULTS: The PREFA questionnaire was found to be feasible and
      simple to complete, reliable, and valid, with excellent responsiveness. Overall,
      the PREFA has demonstrated that it can perform as a stand alone, validated
      assessment of the impact of ED on QoL, assessing areas of QoL not previously
      captured in existing instruments. CONCLUSIONS: The PREFA is suitable for use in
      clinical and research settings as a disease-specific QoL assessment tool.

PMID- 16984067
TI  - Priority setting for research in health care: an application of value of
      information analysis to glycoprotein IIb/Illa antagonists in non-ST elevation
      acute coronary syndrome.
AB  - The purpose of this study is to explain the rationale for the value of
      information approach to priority setting for research and to describe the methods
      intuitively for those familiar with basic decision analytical modeling. A policy
      relevant case study is used to show the feasibility of the method and to
      illustrate the type of output that is generated and how these might be used to
      frame research recommendations. The case study relates to the use of glycoprotein
      Ilb/Illa antagonists for the treatment of patients with non-ST elevation acute
      coronary syndrome. This is an area that recently has been appraised by the
      National Institute for Health and Clinical Excellence.

PMID- 16984068
TI  - Health economic evaluation in Greece.
AB  - OBJECTIVES: There is a growing volume of literature on health economic
      evaluation, with this form of analysis becoming increasingly influential at the
      decision-making level worldwide. The purpose of this study was to review the
      current state of health economic evaluation in Greece, with a view to uncovering
      reasons why its use in this country is limited. METHODS: A search of the NHS
      Economic Evaluation Database was undertaken. The search included cost, cost-of
      illness, cost-minimization, cost-effectiveness, cost-consequences, cost-utility,
      and cost-benefit analyses and was narrowed only to Greek authors undertaking solo
      or joint health economic evaluation in Greece. RESULTS: The search revealed that,
      in Greece, very little health economic evaluation has been undertaken. The main
      reason for the lack of interest is that the current chaotic healthcare system
      structure and financing does not provide the appropriate incentives to stimulate
      a powerful interest in this type of research. This condition is a result of the
      lack of a long-term national health policy and the hesitation of the present and
      past Greek governments to date to proceed to large-scale reforms because of
      political considerations. The Greek governments have also been content with the
      good health indicators being achieved. CONCLUSIONS: Even if it is accepted that
      good health prevails in Greece, slower economic growth rates, an ageing
      population, and the continuous immigration will place increasing pressure on
      healthcare resources and will necessitate a more rational use of these resources.
      Health economic evaluation, by weighing benefits against costs, therefore, has an
      important role to play.

PMID- 16984069
TI  - Cost-effectiveness analysis of strategies for HER2 testing of breast cancer
      patients in France.
AB  - OBJECTIVES: A cost-effectiveness analysis was conducted comparing diagnostic
      strategies for determining the HER2 status of invasive breast carcinomas, as an
      indication for trastuzumab at metastatic relapse. METHODS: A decision tree
      compared five strategies distinguished by (i) the use of immunohistochemical
      (IHC) and/or fluorescent in situ hybridization (FISH) techniques, and (ii) the
      test schedule (at initial diagnosis or metastatic relapse). Most cost and
      effectiveness data came from a French multicentric study of 2,045 patients from
      eight hospitals. We were not able to select final criteria for trastuzumab
      effectiveness, because published data rely on IHC techniques not used in France
      (i.e., HercepTest). We, therefore, selected two intermediate criteria for
      inappropriate treatment at relapse, that is, patients with HER2-amplified tumors
      not receiving trastuzumab (Criterion 1) and HER2-nonamplified tumors improperly
      treated with trastuzumab (Criterion 2). Sensitivity analyses were then performed
      to assess the robustness of the results to (i) discount rate, (ii) cost of FISH,
      and (iii) tissue fixation technique. RESULTS: The strategy using IHC at diagnosis
      was dominated by the four other strategies. Among these approaches, the only
      efficient strategy for both criteria was IHC used alone at metastatic relapse;
      strategies using FISH, or IHC followed by FISH on IHC2+ cases were efficient for
      Criterion 1, whereas IHC followed by FISH on IHC2+ and 3+ cases was efficient for
      Criterion 2. CONCLUSIONS: Determining HER2 status at diagnosis, as an indication
      for trastuzumab at metastatic relapse, incurs substantial incremental costs,
      which do not appear to be justified. No other strategy can be excluded at first.

PMID- 16984070
TI  - On hating to hate.
AB  - Hate may be the most dangerous of all emotions for the survival of the planet.
      The author addresses two questions: What obscures hate when it is actually
      present? and What masquerades as hate but isn't? Using illustrations from a wide
      range of fields, the author contends that discerning hate is both essential and
      far trickier than we think. She concludes by asserting that overcoming hate
      requires imagination. We must learn to imagine a world without hate and unimagine
      a world with hate.

PMID- 16984071
TI  - Sacrifice as a predictor of marital outcomes.
AB  - We investigated the prospective associations between attitudes about sacrifice
      and marital outcomes in 38 married couples. Specifically, a measure of
      satisfaction with sacrifice was proposed to be a potent longitudinal predictor of
      marital adjustment and distress based on existing cross-sectional studies and
      also to mediate the association between commitment and marital adjustment.
      Results demonstrated that attitudes about sacrifice discriminated between couples
      who would become distressed versus nondistressed over time. Sacrifice attitudes
      also predicted the maintenance of relationship adjustment over time even better
      than earlier relationship adjustment. Finally, sacrifice attitudes mediated the
      link between commitment and relationship adjustment for husbands, but not wives.
      Implications for intervention are discussed.

PMID- 16984072
TI  - Sacrifice: a clinical view.

PMID- 16984073
TI  - Success and failure among polygamous families: the experience of wives, husbands,
      and children.
AB  - In this study, we interviewed 10 polygamous families, all residing in a Bedouin
      Arab town in the south of Israel and consisting of 1 husband, 2 wives, and
      children. Five members were interviewed in each family: first wife, second wife,
      the oldest child of the first wife, the oldest child of the second wife, and the
      husband. Five families were considered well-functioning families and five as
      poorly functioning. Findings suggest that polygamy in both well-functioning and
      poorly functioning families is painful, particularly for wives. Yet, there are
      many ways and techniques that enable members of the family to function well.
      Among them are acceptance of polygamy as God's wish or destiny, equal allocation
      of resources among both families by the husband, separation between the two
      households, avoidance of "minor" conflicts and disagreements, maintaining an
      attitude of respect toward the other wife, and allowing open communication among
      all siblings, and among children and the other mother. We discuss the need to
      develop, implement, and evaluate family intervention programs for polygamous
      families among different communities in the world.

PMID- 16984074
TI  - The heart of the matter: a proposal for placing the self of the therapist at the
      center of family therapy research and training.
AB  - As it faces the transition marked by the death or retirement of most of its first
      generation founders, the field of family therapy finds itself still unable to
      answer the critical question of what it is that makes family therapy work. The
      two dominant approaches to answering this question, the common-factors
      perspective and the model-specific factors perspective, remain divided at this
      juncture by a fundamental difference of emphasis between the two. This article
      proposes a way of integrating the two perspectives via the hypothesis that
      therapists achieve maximum effectiveness by committing themselves to a family
      therapy model of proven efficacy whose underlying worldview closely matches their
      own personal worldview. The implications of this hypothesis for the training of
      family therapists are examined.

PMID- 16984075
TI  - Up front and personal: confronting dynamics in the Family Group Conference.
AB  - The Family Group Conference is a participatory model of decision making with
      families in child protection. It is a legal process that brings together the
      family, including the extended family, and the professionals in a family-led
      decision-making forum. Bringing together extended family and professionals to
      discuss child protection concerns can create a highly charged dynamic. Workers
      are challenged by family, family are challenged by workers, and family members
      challenge each other. Practice is also exposed to wider scrutiny as professionals
      also challenge the work. This article briefly describes the development and
      practice of family group conferencing as a family-centred legal process in
      Aotearoa, New Zealand. It then examines the findings of a study exploring the
      dynamics emerging from family group conference practice from the perspective of
      the coordinators who convene them. Family group conferencing as a family
      strengthening practice is discussed.

PMID- 16984076
TI  - Multiple-family group treatment of outpatients with schizophrenia: impact on
      service utilization.
AB  - The impact of multiple-family group treatment (MFGT) on outpatient and inpatient
      mental health service utilization of 97 persons with schizophrenia was
      investigated. Participants were randomly assigned to standard care (n = 44) or
      standard care plus MFGT (n = 53). Service use for a year prior to randomization,
      the 2-year study period, and a 1-year follow-up were examined. Relative to
      standard care participants, the MFGT group had reduced community hospitalization
      during year 1 of the intervention and reduced state hospitalization at follow-up.
      During the intervention period, MFGT participants demonstrated a significant
      increase in outpatient utilization as a direct consequence of the intervention.
      However, when service use was summed across 3 years post-randomization, no group
      differences were observed. Results suggest that implementation of MFGT in a
      community mental health setting reduces inpatient service at specific time
      periods, without significantly increasing outpatient service utilization. These
      findings add to other outcomes from this study that demonstrate decreased
      psychiatric symptoms and caregiver distress.

PMID- 16984078
TI  - [Pleonasm, metaphors and Englishmen].

PMID- 16984077
TI  - The development of a systemic school-based intervention: Marte Meo and
      coordination meetings.
AB  - Antisocial behavior is often persistent, and in addition to causing suffering to
      children and their families, it also poses considerable costs for society.
      Children who display externalizing behavior in their early years run a high risk
      of having severe problems later in life. There is a need for treatment methods
      that may be used in various settings because these children constitute a group
      that is hard to reach with conventional treatment methods. In addition, the
      dropout rate from ordinary treatment is often high. In the present study, a
      systemic school-based model for early detection and intervention among 4-12-year
      old children who displayed externalizing behavior problems was developed and
      examined in a nonrandomized study in the county of Skaraborg in Sweden. The
      intervention was collaborative and included a combination of the Marte Meo model
      and coordination meetings based on systemic theory and practice. Treatment
      effects in the group who had received the intervention were compared with a group
      who had received treatment as usual in their ordinary school setting. Assessments
      were carried out before, and 2 years after, the intervention. For the
      intervention group (N = 33), there was a significant decrease in the children's
      reported symptoms in school and in the home. No decrease in externalizing
      behavior was found in the comparison group (N = 16). There were no dropouts in
      the intervention group after the intervention had begun. The results are
      promising; the study demonstrates that it is possible to work effectively with
      many children who display externalizing behavior problems in a nonclinical
      setting.

PMID- 16984079
TI  - [A simple statistical test. Assessment of treatment effects].

PMID- 16984080
TI  - [Food intolerance--etiology of functional disorders and therapeutic
      possibilities].
AB  - Patients often complain about food intolerances and accuse them of causing
      diarrhea, constipation, meteorism, flatulence and abdominal pain. With alarm
      symptoms, patients usually suffer from structural diseases, which have to be
      clarified immediately by extensive diagnostic steps. With no alarm symptoms
      present, patients usually suffer from functional disorders. Their workup should
      be done stepwise. Therapy is dependent on the underlying disorder and often
      symptom-adapted. General measures of prevention for food-preparation and
      nutrition are important.

PMID- 16984081
TI  - [Illnesses by the human respiratory syncytial virus].
AB  - Human respiratory syncytial virus (HRSV) is a single-stranded, enveloped RNA
      virus of the Paramyxoviridae family. Worldwide, HRSV represents the leading cause
      of respiratory tract infections in infants and young children. Approximately up
      to 70% of infants are infected during their first year of life. Recently, an
      increasing number of reports have described the causal association of HRSV with
      several respiratory infections in adult patients. Serious illnesses have been
      documented in especially immunocompromised hosts or in individuals revealing
      immunosuppressive treatment regimes. Viable options for the prevention or
      treatment of HRSV infections are limited. Current guidelines do no contain
      specific recommendations for the causal treatment of HRSV infections.
      Immunoprophylactic and hygienic measures represent the most effective strategies
      for prevention of disease.

PMID- 16984082
TI  - [Carnosine--an endogenous antioxidant and tissue protective factor].

PMID- 16984083
TI  - [How long can acne therapeutics be applied?].

PMID- 16984084
TI  - Robustness analysis of biochemical network models.
AB  - Biological systems that have been experimentally verified to be robust to
      significant changes in their environments require mathematical models that are
      themselves robust. In this context, a necessary condition for model robustness is
      that the model dynamics should not be sensitive to small variations in the
      model's parameters. Robustness analysis problems of this type have been
      extensively studied in the field of robust control theory and have been found to
      be very difficult to solve in general. The authors describe how some tools from
      robust control theory and nonlinear optimisation can be used to analyse the
      robustness of a recently proposed model of the molecular network underlying
      adenosine 3',5'-cyclic monophosphate (cAMP) oscillations observed in fields of
      chemotactic Dictyostelium cells. The network model, which consists of a system of
      seven coupled nonlinear differential equations, accurately reproduces the
      spontaneous oscillations in cAMP observed during the early development of D.
      discoideum. The analysis by the authors reveals, however, that very small
      variations in the model parameters can effectively destroy the required
      oscillatory dynamics. A biological interpretation of the analysis results is that
      correct functioning of a particular positive feedback loop in the proposed model
      is crucial to maintaining the required oscillatory dynamics.

PMID- 16984085
TI  - Dealing with gene expression missing data.
AB  - Compared evaluation of different methods is presented for estimating missing
      values in microarray data: weighted K-nearest neighbours imputation (KNNimpute),
      regression-based methods such as local least squares imputation (LLSimpute) and
      partial least squares imputation (PLSimpute) and Bayesian principal component
      analysis (BPCA). The influence in prediction accuracy of some factors, such as
      methods' parameters, type of data relationships used in the estimation process
      (i.e. row-wise, column-wise or both), missing rate and pattern and type of
      experiment [time series (TS), non-time series (NTS) or mixed (MIX) experiments]
      is elucidated. Improvements based on the iterative use of data (iterative LLS and
      PLS imputation--ILLSimpute and IPLSimpute), the need to perform initial
      imputations (modified PLS and Helland PLS imputation--MPLSimpute and HPLSimpute)
      and the type of relationships employed (KNNarray, LLSarray, HPLSarray and
      alternating PLS--APLSimpute) are proposed. Overall, it is shown that data set
      properties (type of experiment, missing rate and pattern) affect the data
      similarity structure, therefore influencing the methods' performance. LLSimpute
      and ILLSimpute are preferable in the presence of data with a stronger similarity
      structure (TS and MIX experiments), whereas PLS-based methods (MPLSimpute,
      IPLSimpute and APLSimpute) are preferable when estimating NTS missing data.

PMID- 16984086
TI  - Signal propagation in nonlinear stochastic gene regulatory networks.
AB  - The ability to build genetic circuits with a reproducible response to external
      stimuli depends on the experimental and theoretical methods used in the process.
      A theoretical formalism that describes the response of a nonlinear stochastic
      genetic network to the external stimuli (input signals), is proposed. Two
      applications are studied in detail: the design of a logic pulse and the
      interference of three signal generators in the E2F1 regulatory element. The gene
      interactions are presented using molecular diagrams that have a precise
      mathematical structure and retain the biological meaning of the processes.

PMID- 16984087
TI  - Delayed effects of enalapril on structural characteristics of the glomerular
      apparatus in the kidneys of NISAG rats.
AB  - Structural characteristics of renal glomeruli were studied in adult hypertensive
      NISAG rats (hereditary stress-induced hypertension) receiving antihypertensive
      drug enalapril, an inhibitor of angiotensin-converting enzyme, on days 28-58 of
      life. Treatment with enalapril (25 mg/kg perorally) in the early period of
      postnatal ontogeny produced delayed hypotensive and nephroprotective effects.

PMID- 16984088
TI  - Effects of semax against the background of dopaminergic receptor blockade with
      haloperidol.
AB  - We studied the neurotropic effects of ACTH(4-10) analog semax against the
      background of dopaminergic receptors blockade with haloperidol. Intranasal
      administration of semax (0.05, 0.2, and 0.6 mg/kg) produced virtually no effect
      on disturbances of orientation and exploratory reactions and motor activity
      caused by intraperitoneal injection of 0.2 mg/kg haloperidol. By contrast,
      preliminary administration of 0.05 mg/kg semax prevented haloperidol-induced
      disturbances in active avoidance conditioning.

PMID- 16984089
TI  - Effect of enalapril injected in the early period of postnatal ontogeny on
      structure of adrenal glands in mature hypertensive NISAG rats.
AB  - Blood pressure in 6-month hypertensive NISAG rats daily treated with enalapril in
      the early postnatal period was lower than in control rats. Enalapril produced
      significant morphological alterations only in the zona glomerulosa of the adrenal
      cortex. The volumes of this area and the corresponding endocrine cells were lower
      than in the control. Enalapril produced a delayed modifying effect on the
      structure of the adrenal zona glomerulosa by moderating hyperplasic alterations,
      which are characteristic of intact mature NISAG rats.

PMID- 16984090
TI  - Hydruric response in Wistar and vasopressin-deficient Brattleboro rats to water
      load under conditions of increased brain serotonin level.
AB  - The hydruric response to water load in Wistar rats and homozygous Brattleboro
      rats with a hereditary defect in the synthesis of vasopressin was studied under
      conditions of increased brain serotonin level. Serotonin prevented the reduction
      in reabsorption of osmotically free water in normal rats, but had no effect in
      vasopressin-deficient Brattleboro rats. Our results suggest that serotonin
      stimulates vasopressin secretion and interacts with the vasopressinergic system
      during the realization of osmotic regulation.

PMID- 16984091
TI  - Effect of dimephosphon on functional recovery of damaged spinal cord.
AB  - The effect of endolumbar dimephosphon perfusion in dogs with spinal cord
      contusion was studied by means of transcranial magnetic stimulation and
      stimulation electromyography. Treatment with dimephosphon contributed to
      preservation of conduction function of the spinal cord and decrease in
      excitability of spinal motoneurons in the perifocal zone.

PMID- 16984092
TI  - Analgesic effect of corticotropin-releasing hormone: involvement of the
      hypothalamic-pituitary-adrenocortical axis into its realization.
AB  - Involvement of hypothalamic-pituitary-adrenocortical axis into the analgesic
      effect of corticotropin-releasing hormone after its systemic administration was
      studied in experiments on rats. Pharmacological blockade of the hypothalamic
      pituitary-adrenocortical axis decreased the duration and degree of the analgesic
      effect of corticotropin-releasing hormone. This analgesic effect can be mediated
      via two pathways: related to hormones of the hypothalamic-pituitary
      adrenocortical axis and independent of these hormones.

PMID- 16984093
TI  - Chronodromotropic coordination in cats.
AB  - The coordinated nervous influences on HR and atrioventricular conduction velocity
      (chronodromotropic coordination) were examined in wakeful cats. The wave
      structure and reflex reactions of RR and atrioventricular (AV) intervals to
      stress noise stimulation were studied under normal conditions and during the
      action of blockers of peripheral receptors in ANS. Variations of both intervals
      had similar wave structure (power spectrum) and similar reactions to noise
      stimulus. Atropine pronouncedly decreased all components of the spectra in the
      high, low, and very low frequency ranges. It eliminated the reactions of both
      intervals to noise stimulation. In RR intervals, the high-frequency spectrum
      component decreased more strongly than the low-frequency ones. By contrast, in AV
      intervals atropine most greatly decreased the very-low-spectrum component, while
      the high frequency was decreased less of all. Propranolol produced no effect on
      the response to noise. It did not decrease components of the wave structure in
      both intervals, except for the very-low-frequency peak of AV interval. The
      nervous chronotropic and dromotropic influences were largely coordinated,
      although they were not obligatorily parallel.

PMID- 16984094
TI  - Effect of gonadotropin-releasing hormone analogue on thermal nociception in mice.
AB  - Intraperitoneal treatment with an analogue of gonadotropin-releasing hormone in
      doses of 0.004-450 microg/kg produced an analgesic effect on male mice in the hot
      plate test. Castration significantly elevated the nociceptive thresholds. In
      castrated mice the effects of the test peptide were less pronounced and had an
      algesic nature. Our results indicate that these effects depend on functional
      activity of the hypothalamic-pituitary-gonadal axis.

PMID- 16984095
TI  - Interhemispheric EEG asymmetry in patients with insomnia during nocturnal sleep.
AB  - Sleep EEG was recorded and analyzed in patients with neurotic insomnia. It was
      found that interhemispheric asymmetry in the same individual can vary during
      sleep from right-hemispheric to left-hemispheric. Interhemispheric EEG asymmetry
      is closely related to the stage of sleep. The development of left-hemisphere or
      right-hemisphere asymmetry is mainly determined by activity of the right
      hemisphere. The development of interhemispheric asymmetry during wakefulness,
      stages 1 and 2 sleep, and delta sleep is mediated by common mechanisms.

PMID- 16984096
TI  - Effect of antibodies against serotonin, bovine serum albumin, and complete
      Freund's adjuvant on mice subjected to acute immobilization stress.
AB  - Nonspecific immunomodulators (complete Freund's adjuvant and bovine serum
      albumin) produced an antistress effect on mice during immobilization stress.
      Immunization with a serotonin-protein conjugate produced no antistress effect.

PMID- 16984097
TI  - Apoptosis and proliferative activity in endometrium during peritoneal
      endometriosis.
AB  - Apoptosis and proliferative activity of the glandular epithelium and endometrial
      stroma in patients with peritoneal endometriosis and in women of reproductive age
      without endometriosis were studied at various stages of menstrual cycle.
      Differences in the intensity of apoptosis were revealed manifesting in changed
      expression of proteins in the glandular epithelium of patients with endometriosis
      during the secretory phase of the menstrual cycle compared to normal.
      Proliferative activity of the glandular epithelium in the proliferative phase was
      higher than in the secretory phase. Our results suggest that the imbalance
      between apoptosis proteins in the endometrium plays a role in the pathogenesis of
      peritoneal endometriosis.

PMID- 16984098
TI  - Effect of indomethacin on kainic acid-induced memory disorders.
AB  - Single administration of kainic acid to Wistar rats impaired quenching of the
      conditioned response and increased the number of perseverative reactions 2 weeks
      postinjection. Indomethacin prevented behavioral disturbances induced by kainic
      acid.

PMID- 16984100
TI  - Production of vascular endothelial growth factor and endothelin in the placenta
      and umbilical cord during normal and complicated pregnancy.
AB  - The concentrations of vascular endothelial growth factor and endothelin in the
      placenta progressively increased during normal pregnancy. Production of vascular
      endothelial growth factor and endothelin in the placenta exceeded the normal
      during trimester I miscarriage and trimester III premature birth accompanied by
      intrauterine hypoxia. The concentration of these vasoactive substances during
      premature birth also increased in the umbilical cord. The compensatory decrease
      in the concentrations of vascular endothelial growth factor and endothelin in the
      placenta and umbilical cord was observed during full-term pregnancy with
      threatened abortion.

PMID- 16984099
TI  - Role of free nitrogen and oxygen radicals in the pathogenesis of
      lipopolysaccharide-induced endotoxemia.
AB  - We studied molecular mechanisms of changes in oxidative metabolism under
      conditions of experimental lipopolysaccharide-induced endotoxemia. Generation of
      reactive nitrogen and oxygen species in mice increased 18 h after treatment with
      lipopolysaccharide. These changes contributed to inactivation of enzymes and
      enzyme complexes (ribonucleotide reductase, NADH-ubiquinone oxidoreductase, and
      cytochrome c oxidase), dysfunction of the mitochondrial electron transport chain,
      and development of oxidative stress. Plaferon LB protected mice from the toxic
      effect of lipopolysaccharide.

PMID- 16984101
TI  - Effect of ultraviolet B irradiation on immobilization stress-induced changes in
      the protective systems of C57Bl/6 mice.
AB  - We studied the effect of ultraviolet B irradiation on superoxide dismutase
      activity, ceruloplasmin level in the plasma, and steroid hormone concentration in
      the adrenal glands of C57Bl/6 mice subjected to immobilization stress.
      Ultraviolet B irradiation did not abolish the increase in superoxide dismutase
      activity, but decreased ceruloplasmin level in the plasma and corticosteroid
      concentration in the adrenal glands of mice exposed to immobilization stress.

PMID- 16984102
TI  - Kyotorphin suppresses proliferation and Ca2+ signaling in brown preadipocytes.
AB  - A positive correlation was revealed between stimulation of protein and DNA
      synthesis in preadipocytes by norepinephrine or neokyotorphin and intracellular
      Ca2+ concentration in these cells. Kyotorphin abolished the stimulatory effect of
      norepinephrine on proliferation of cultured cells and cold-induced [3H]-thymidine
      incorporation into DNA of mouse brown adipose tissue in vivo. These changes
      correlated with peptide-induced suppression of slow calcium signaling in
      preadipocytes.

PMID- 16984103
TI  - Changed morphine sensitivity of morphine-dependent rats after laser exposure of
      the cerebral prefrontal cortex.
AB  - We studied the effect of bilateral laser exposure of the cerebral prefrontal
      cortex in morphine-dependent rats on their sensitivity to positive reinforcing
      and toxic effect of morphine. Laser exposure led to partial deafferentation of
      the cingulum. Exposure of the anterior and central areas of the prefrontal cortex
      stimulated self-administration of low morphine doses and had no effect on self
      administration of high concentrations. Exposure of the posterior area of the
      prefrontal cortex did not appreciably change self-administration of medium and
      low morphine doses, but self-administration of high doses significantly
      increased. Exposure of the anterior area of the prefrontal cortex significantly
      decreased the sensitivity to the positive reinforcing effect of morphine.
      Exposure of the posterior prefrontal cortex decreased the sensitivity to the
      toxic effect of morphine.

PMID- 16984104
TI  - Natural polysaccharide carrageenan inhibits toxic effect of gram-negative
      bacterial endotoxins.
AB  - The protective effect of polysaccharide carrageenan on the damaging effect of
      endotoxins of gram-negative bacteria was studied in vivo and in vitro.
      Carrageenan increased mouse resistance to the toxic effect of LPS. The degree of
      protection depended on polysaccharide concentration and administration time and
      route. Pretreatment of donor platelets with carrageenan reduced their aggregation
      activity caused by cooperative effect of LPS and ADP.

PMID- 16984105
TI  - Effects of hydroxysterols and atorvastatin on lipopolysaccharide-induced
      secretion of tumor necrosis factor and interleukin-10 by mouse macrophages.
AB  - Preincubation of macrophages with atorvastatin, cholesterol, 25-, 27
      hydroxycholesterol, and 7-ketocholesterol reduced the level of TNF-alpha to 10,
      61, 13, 64.5, and 82%, respectively. Addition of mevalonate to the preincubation
      medium canceled the effects atorvastatin, cholesterol, and 7-ketocholesterol, but
      not the effects of 25- and 27-hydroxycholesterols. Atorvastatin increased the
      level of IL-10 by 41%, while 7-ketocholesterol and 25-hydroxycholesterol
      inhibited its secretion by 48 and 55%.

PMID- 16984106
TI  - Relationship between spermatozoon movement velocity and expression of testicular
      isoform of angiotensin-converting enzyme on their surface.
AB  - The expression of testicular isoform of angiotensin-converting enzyme on the
      surface of human spermatozoa was evaluated by flow cytometry with monoclonal
      antibodies to epitopes of C-terminal domain of human angiotensin-converting
      enzyme and the mean path, mean curvilinear and straight-line velocities were
      determined by computer analysis of spermatozoon movement. A positive correlation
      between the expression of testicular isoform of angiotensin-converting enzyme on
      the cell surface and spermatozoon movement velocity was revealed.

PMID- 16984107
TI  - Enzymes of estrogen metabolism in endometrial cancer.
AB  - Activities of estrogen metabolism enzymes (aromatase, 2- and 4-estrogen
      hydroxylases, catechol-O-methyltransferase, and glutathione transferase) were
      studied by modern biochemical methods in tumors of patients with endometrial
      cancer. Relationships between enzyme activities and body weight index, age of
      menarche, stage of the disease, tumor histotype, differentiation degree, and
      depth of invasion into the myometrium were detected. The detected relationships
      between enzyme activities and serum concentrations of estradiol and progesterone
      and level of estrogen receptors in tumor tissue attest to hormone dependence of
      aromatase, estrogen hydroxylases, and glutathione transferase.

PMID- 16984108
TI  - Genetic status of p53 in stomach cancer: somatic mutations and polymorphism of
      codon 72.
AB  - The incidence of somatic mutagenesis of p53 oncosuppressor protein in malignant
      tumors of the stomach and genetic polymorphism of p53 were studied in patients
      with stomach cancer on DNA samples isolated from tumor tissues obtained during
      surgery. The incidence of Pro/Pro genotype increased in the patients, while the
      percentage of Arg/Pro heterozygotes was markedly lower compared to long-living
      persons without cancer. The incidence of p53 somatic mutations in exons 5, 7, 8
      was 70.8%; multiple mutations were detected in half of the examined patients. The
      relationship between the intensity of p53 mutagenesis and histological structure
      of the tumor was detected. The contribution of p53 genetic status to the risk of
      stomach cancer can be more effectively evaluated on DNA samples isolated from not
      only tumor cells, but also from normal tissues. The effects of epigenetic factors
      determining the intensity of somatic mutagenesis of p53 in tumors should be taken
      into account.

PMID- 16984109
TI  - Serum activity of matrix metalloproteinases -2 and -9.
AB  - Matrix metalloproteinases belong to the key effectors of tissue remodeling in
      health and disease. Matrix metalloproteinases -2 and -9, the most prevalent
      representatives of this family, are expressed in the endometrium. Chronic
      endometritis concomitant with sterility and spontaneous abortions is associated
      with decreased content of matrix metalloproteinases in the endometrium. Chronic
      endometritis combined with sterility correlates with decreased serum activities
      of matrix metalloproteinases -2 and -9, which returns to normal after recovery.
      Measurements of serum activities of matrix metalloproteinases -2 and -9 are
      proposed for monitoring of the dynamics and treatment efficiency in chronic
      endometritis.

PMID- 16984110
TI  - Effects of structural and "mixed" isomers of Glu-Trp dipeptide on normal
      hemopoietic stem cells.
AB  - We studied the effects of optical (dd-, ll-, dl-, and ld-dipeptides with alpha
      bond, EW) structural isomers and cyclic (dd-, ll-, dl-, and ld-dipeptides with
      gamma-bond, iEW) analogs of Glu-Trp synthetic dipeptide on the population of
      normal hemopoietic stem cells. Dipeptides containing lGlu (lGlu-lTrp, lGlu-dTrp)
      injected to mice were inert towards committed bone marrow CFU-S; dGlu-containing
      dipeptides (dGlu-dTrp, dGlu-lTrp) inhibited the growth of CFU-S-8; and LiGlu-dTrp
      stimulated these cells. Inhibitory or stimulatory effects of optical and chemical
      isomers of Glu-Trp dipeptide are determined by optical orientation and nature of
      peptide bond of Glu residue. The effects of cyclic and mixed peptides towards
      colony formation are similar to those of the corresponding linear dipeptides.

PMID- 16984111
TI  - Mechanisms of formation of micronuclei in somatic cells of tailless amphibians
      normally and under the effect of N-nitroso-N-methylcarbamide.
AB  - We studied the relationship between mitotic regimen and incidence of micronuclei
      in liver and bone marrow cells of tailless amphibians under the effect of
      genotoxic carcinogen N-nitroso-N-methylcarbamide. Micronuclei appeared in
      amphibian somatic cells normally and after mutagenic exposure as a result of
      abnormal mitosis and of "interphase chromatin diminution". This latter variant
      was most incident in lymphoid cells, presenting as "caudate nuclei", which should
      be taken into consideration when interpreting findings of micronucleus analysis.

PMID- 16984112
TI  - Hydrolase and oxidoreductase activities in peripheral blood lymphocytes in
      combined exposure to biological allergens and sulfur dioxide.
AB  - Differences in the metabolic status of peripheral blood lymphocytes were observed
      after exposure of intact guinea pigs and animals sensitized with biological
      allergens to sulfur dioxide. When sensitization was complicated by chemical
      exposure, enzyme activities in lymphocytes depended on the type of allergen and
      degree of hypersensitivity.

PMID- 16984113
TI  - Effect of hydrogen peroxide on ejection of cell nucleus from pigeon erythrocytes
      and state of membrane lipids.
AB  - The nuclei are ejected from the pigeon erythrocytes and apoptotic vesicles form
      in these cells in the presence of hydrogen peroxide. Hydrogen peroxide
      intensifies LPO processes and changes phospholipid content. The relative content
      of phosphatidylcholine, sphingomyelin, and phosphatidylserine decreased, while
      that of phosphatidylethanolamine and lisophosphatidylcholine increased. The
      content of unsaturated fatty acids also decreased under these conditions.
      Presumably, these changes in the lipid phase of the erythrocyte membrane are a
      mechanism preparing the cell to nucleus ejection and apoptosis.

PMID- 16984114
TI  - Disturbed assembly of human cerebral microtubules in Alzheimer's disease.
AB  - It is shown for the first time that microtubular proteins isolated from the brain
      of patients with Alzheimer's disease can in vitro polymerize into microtubules
      with abnormal structure.

PMID- 16984115
TI  - Regression analysis of relationship between liver weight and body weight after
      partial hepatectomy in rats.
AB  - A method for evaluation of the initial weight of the liver is developed for
      calculating the regeneration coefficient after partial hepatectomy on the basis
      of linear regression analysis. Experiments on rats showed that the model
      reflecting the relationship between liver weight and body weight for calculation
      of regeneration coefficient after partial resection of the liver expressed by the
      equation P0=0.033 x M can be used for screening of potential hepatoprotectors for
      quantitative evaluation of the regeneration processes.

PMID- 16984116
TI  - Experimental model of hemorrhagic stroke: rabbit immunization with HL-60
      promyelocytic cell differentiation factor.
AB  - Rabbits immunized with synthetic HLDF differentiation factor developed
      hemorrhagic stroke with thrombosis of small cerebral vessels and destruction of
      vascular endotheliocytes. The severity of stroke correlated with serum level of
      antibodies to differentiation factor. The role of different sites of HLDF
      molecule in the induction of clinical signs of hemorrhagic stroke was studied.

PMID- 16984117
TI  - HER2 specific tumor targeting with dendrimer conjugated anti-HER2 mAb.
AB  - In the present study, we report the synthesis and human growth factor receptor-2
      (HER2) specific tumor targeting properties of a dendrimer conjugated to anti-HER2
      mAb (monoclonal antibody) conjugate. The polyamidoamine (PAMAM) dendrimer
      generation five (G5) was labeled with alexaFluor 488 and conjugated to anti-HER2
      mAb. The binding and internalization of the antibody-conjugated dendrimer to HER2
      expressing cells was evaluated by flow cytometry and confocal microscopy.
      Uniquely, the conjugate demonstrated cellular uptake and internalization in HER2
      expressing cells as compared to free antibody. The time course of internalization
      and blocking experiments with free antibody suggest that the rapid and efficient
      cellular internalization of the dendrimer-antibody conjugate was achieved without
      alterations in specificity of targeting. Animal studies demonstrated that the
      conjugate targets HER2-expressing tumors.

PMID- 16984118
TI  - Amino-terminal dimerization of peptides on the solid support. Synthesis and
      biological activity of the immunosuppressive HLA-DR fragments linked by
      poly(ethylene glycol)s.
AB  - The nonapeptide fragment of the HLA-DR molecule, located in the exposed loop of
      the beta chain (164-172) and having the sequence VPRSGEVYT, suppresses the immune
      response. On the basis of the three-dimensional structure of the HLA-DR
      superdimer, we designed new dimeric analogs in which the VPRSGEVYT peptides are
      linked through their N-termini by poly(ethylene glycol) linkers of different
      lengths and are able to mimic the dimeric nature of the immunosuppressive
      fragments of HLA class II molecules. The analogs were synthesized using standard
      solid-phase peptide synthesis protocols. The dimerization was achieved by cross
      linking the N-terminal positions of the peptides, attached to an MBHA resin, with
      alpha,omega-bis(acetic acid) poly(ethylene glycol), activated by esterification
      with pentafluorophenol. Our results demonstrate that the amino-terminal
      dimerization of the peptide results in enhanced immunosuppressive activity and
      that the potency of the conjugates depends on the length of the poly(ethylene
      glycol) linker. MS/MS analysis of the obtained dimeric peptides is also
      presented.

PMID- 16984119
TI  - Immobilization and clustering of structurally defined oligosaccharides for sugar
      chips: an improved method for surface plasmon resonance analysis of protein
      carbohydrate interactions.
AB  - Oligosaccharides are increasingly being recognized as important partners in
      receptor-ligand binding and cellular signaling. Surface plasmon resonance (SPR)
      is a very powerful tool for the real-time study of the specific interactions
      between biological molecules. We report here an advanced method for the
      immobilization of oligosaccharides in clustered structures for SPR and their
      application to the analysis of heparin-protein interactions. Reductive amination
      reactions and linker molecules were designed and optimized. Using mono-, tri-, or
      tetravalent linker compounds, we incorporated synthetic structurally defined
      disaccharide units of heparin and immobilized them as ligands for SPR. Their
      binding to an important hemostatic protein, von Willebrand factor (vWf), and its
      known heparin-binding domain was quantitatively analyzed. These multivalent
      ligand conjugates exhibited reproducible binding behavior, with consistency of
      the surface conditions of the SPR chip. This novel technique for oligosaccharide
      immobilization in SPR studies is accurate, specific, and easily applicable to
      both synthetic and naturally derived oligosaccharides.

PMID- 16984120
TI  - Synthesis and in vitro characterization of antigen-conjugated polysaccharide as a
      CpG DNA carrier.
AB  - Oligodeoxynucleotides containing unmethylated CpG sequences (CpG DNAs) are known
      as an immune adjuvant. CpG DNAs coupled with a particular antigen enabling both
      CpG DNA and antigen delivery to the same antigen-presenting cell have been shown
      to be more effective. Based on our previous finding that beta-(1-->3)-D-glucan
      schizophyllan (SPG) can be used as a CpG DNA carrier, here we present the
      synthesis of an antigen-conjugated SPG and the characterization of the conjugate.
      Ovalbumin (OVA, 43 kDa) was used as a model antigen, and two OVA were conjugated
      to one SPG molecule (M(w) = 150,000), denoted by OVA-SPG. Circular dichroism and
      gel electrophoresis showed that OVA-SPG could form a complex with a (dA)(40)
      tailed CpG DNA at the 3' end (1,668-(dA)(40)). When OVA-SPG was added to
      macrophages (J774.A1), the amount of the ingested OVA-SPG was increased compared
      with that of OVA itself, suggesting that Dectin-1 (proinflammatory nonopsonic
      receptor for beta-glucans) is involved to ingest OVA-SPG. Furthermore, the
      complex of the conjugate and DNA was co-localized in the same vesicles, implying
      that OVA (antigen) and CpG DNA (adjuvant) were ingested into the cell at the same
      time. This paper shows that OVA-SPG can be used as a CpG DNA carrier to induce
      antigen-specific immune responses.

PMID- 16984121
TI  - Receptor-targeted liposomal delivery of boron-containing cholesterol mimics for
      boron neutron capture therapy (BNCT).
AB  - Liposomes have been a main focus of tumor-selective boron delivery strategies in
      boron neutron capture therapy (BNCT), a binary method for the treatment of cancer
      that is based on the nuclear reaction between boron atoms and low-energy thermal
      neutrons. Three novel carboranyl cholesterol derivatives were prepared as lipid
      bilayer components for the construction of nontargeted and receptor-targeted
      boronated liposomes for BNCT. A major structural feature of these novel boronated
      cholesterol mimics is the replacement of the B and the C ring of cholesterol with
      a carborane cluster. Computational analyses indicated that all three boronated
      compounds have structural features and physicochemical properties that are very
      similar to those of cholesterol. One of the synthesized boronated cholesterol
      mimics was stably incorporated into non-, folate receptor (FR)-, and vascular
      endothelial growth factor receptor-2 (VEGFR-2)-targeted liposomes. No major
      differences were found in appearance, size distribution, and lamellarity between
      conventional dipalmitoylphosphatidylcholine (DPPC)/cholesterol liposomes,
      nontargeted, and FR-targeted liposomal formulations of this carboranyl
      cholesterol derivative. FR-targeted boronated liposomes were taken up extensively
      in FR overexpressing KB cells in vitro, and the uptake was effectively blocked in
      the presence of free folate. In contrast, a boronated cholesterol mimic
      incorporated into nontargeted liposomes showed significantly lower cellular
      uptake. There was no apparent in vitro cytotoxicity in FR overexpressing KB cells
      and VEGFR-2 overexpressing 293/KDR cells when these were incubated with boronated
      FR- and (VEGFR-2)-targeted liposomes, respectively, although the former
      accumulated extensively in KB cells and the latter effectively interacted with
      VEGFR-2 by causing autophosphorylation and protecting 293/KDR cells from SLT
      (Shiga-like toxin)-VEGF cytotoxicity.

PMID- 16984122
TI  - Cholesterol-linked fluorescent molecular beacons with enhanced cell permeability.
AB  - We appended pyrene units covalently onto adenosine (forming A(P) units) and then
      incorporated them into oligonucleotides such that they were positioned in
      complementary locations in opposite strands in the middle positions of hairpin
      stems. System 1 (A(P)A(P)) behaves as an effective molecular beacon (MB) that
      changes color from green to blue upon duplex formation. In addition, we attached
      a cholesterol unit to a free terminus of one of these hairpins; this approach
      enhanced the cellular delivery of the modified MB relative to those encountered
      when using conventional transfection methods. These structurally simple
      cholesterol-based MB systems, which can be synthesized very efficiently, have
      good potential for opening up new and exciting opportunities in the field of in
      vivo biosensors.

PMID- 16984123
TI  - DNA binding to protein-gold nanocrystal conjugates.
AB  - The E. coli DNA binding protein lac repressor (LacI) and a derivative with a
      designed thiol (T334C) were developed as gold nanocrystal conjugates to assess
      the effects of conjugation on DNA binding function. The designed derivative was
      engineered with a solvent-accessible thiol to promote oriented conjugation,
      avoiding obstruction of the DNA-binding domain by the nanocrystal. Analytical
      ultracentrifugation (AU) and electrophoretic mobility shift assays (EMSA) were
      used to evaluate the ability of conjugated repressors to bind the natural
      operator DNA sequence O(1). The results show that LacI does not retain
      significant DNA binding function when conjugated to gold nanocrystals, presumably
      because the basic DNA-binding domain is the site for nonspecific conjugation.
      T334C, with the potential for both directed and nonspecific conjugation, shows
      enhanced interaction with O(1) when conjugated. Interestingly, the order of
      component addition is a key factor in producing functional lac repressor
      conjugates.

PMID- 16984124
TI  - Biodegradable polymeric vectors for gene delivery to human endothelial cells.
AB  - Endothelial cells are an important cell type to both cardiovascular disease and
      cancer, as they play critical roles in vascular function and angiogenesis.
      However, effective and safe gene delivery to primary endothelial cells in the
      presence of serum proteins is known to be particularly challenging. A library of
      biodegradable poly(beta-amino esters) was synthesized for use as potential
      vectors. Promising vectors were optimized for high efficacy and low cytotoxicity
      to human umbilical vein endothelial cells (HUVECs) in serum. Vector parameters
      including polymer type, polymer weight, and DNA loading were varied, and
      biophysical properties including particle size, zeta potential, and particle
      stability over time were studied. While many of the poly(beta-amino ester)
      vectors have similar biophysical properties in the presence of buffer, their
      biophysical properties changed differentially in the presence of serum proteins,
      and the properties of these serum-interacting particles correlated to
      transfection efficacy. Leading poly(beta-amino ester) vectors were found to
      transfect HUVECs in the presence of serum significantly higher (47 +/- 9%
      positive, n = 10) than the best commercially available transfection reagents
      including jetPEI (p < 0.001) and Lipofectamine 2000 (p < 0.01). These results
      demonstrate the potential of a new class of biomaterials, poly(beta-amino
      esters), for effective human endothelial cell gene therapy.

PMID- 16984125
TI  - Preparation of bioactive and surface functional oligomannosyl neoglycoprotein
      using extracellular pH-sensitive glycosylation of mutant lysozyme having N-linked
      signal sequence in yeast.
AB  - Bioactive oligomannosyl lysozyme with improved surface functionalities was
      successfully prepared by using an extracellular pH-sensitive glycosylation system
      for heterogeneous protein in yeast cell. A recombinant Saccharomyces cerevisiae
      carrying a mutant lysozyme gene encoding the signal sequence of an N-linked
      glycosylation site at position 49 was cultivated in various pH conditions to
      investigate the effects of extracellular pH on the glycosylation patterns and the
      expression of the protein. A large polymannose (Man(310)GlcNAc(2)) chain-linked
      lysozyme was predominantly expressed accompanied by small amounts of a core-type
      oligomannose chain (Man(14)GlcNAc(2))-linked lysozyme in the yeast medium where
      the extracellular pH was kept at 3.5 or above, while an oligomannose chain
      lysozyme was preferentially expressed in the yeast medium where the pH was less
      than 3. The lytic activities of the oligomannosyl and the polymannosyl lysozymes
      were found to be 70.4 and 5.1%, respectively, of the wild-type lysozyme when
      Micrococcus lysodeikticus cells were used as the substrate. The enzymatic
      activity of the oligomannosyl lysozyme was totally conserved for the glycolysis
      assay with a soluble substrate, glycol chitin, whereas that of the polymannosyl
      lysozyme was not. After heating the sample up to 95 degrees C at pH 7.0 where no
      visible protein coagulation was observed, thermostability of the enzymatic
      activity of the oligomannosyl lysozyme was drastically improved with more than
      60% of residual lytic activity. Emulsifying properties of the protein also were
      highly improved by the oligomannosylation, in which the emulsifying activity was
      3.2 times higher than that of the wild-type protein. Corresponding to the
      increase of the surface functionalities, the surface tension of the oligomannosyl
      protein exhibited a significantly (p < 0.05) lower value compared to that of the
      wild-type. By using the lower pH medium at 3.0, it was revealed that a
      substantial amount (0.31 mg/L) of the oligomannosyl lysozyme was successfully
      obtained in the culture medium. Therefore, the extracellular pH-sensitive
      glycosylation system can be used to obtain bioactive and surface functional
      neoglycoproteins.

PMID- 16984126
TI  - Transcription inhibition using oligonucleotide-modified gold nanoparticles.
AB  - The capture of T7 RNA polymerase using double-stranded promoter DNA on the
      surface of gold nanoparticles has been demonstrated. The competitive binding and
      inhibition of T7 RNA polymerase due to specific interactions on the nanoparticle
      surface represents a transcription factor decoy approach in a model system. The
      efficiency of inhibition was determined for various nanoparticle sizes, surface
      coverage, and linker length for double-stranded promoter DNA on gold
      nanoparticles. The experiments provide a basis for determining the accessibility
      of binding sites on nanoparticle surfaces for applications involving cell
      targeting or the use of nanoparticles as binding agents in solution.

PMID- 16984127
TI  - Oligonucleotide microarrays: immobilization of phosphorylated oligonucleotides on
      epoxylated surface.
AB  - A facile and efficient method for direct immobilization of phosphorylated
      oligonucleotides on an epoxy-activated glass surface is described. The new
      immobilization strategy has been analyzed for its performance in DNA microarray
      under both microwave and thermal conditions. It reflects high immobilization
      efficiency ( approximately 23%), and signal-to-noise ratio ( approximately 98)
      and resulted in high hybridization efficiency ( approximately 36%) in comparison
      to those obtained with standard methods, viz., NTMTA ( approximately 9.76%) and
      epoxide-amine ( approximately 9.82%). The probes immobilized through the new
      strategy were found to be heat-stable, since the performance of microarray
      decreased by only approximately 7% after subjecting it to 20 PCR-like heat
      cycles, suggesting that the chemistry could be used in integrated PCR/microarray
      devices. The immobilization of probes following the proposed chemistry resulted
      in spots of superior quality in terms of spot morphology, spot homogeneity, and
      signal reproducibility. The constructed microarrays have been successfully used
      for the discrimination of nucleotide mismatches. In conclusion, these features
      make the new immobilization strategy ideal for facile, efficient, and cost
      effective manufacturing of DNA microarrays.

PMID- 16984128
TI  - Trastuzumab-polyethylenimine-polyethylene glycol conjugates for targeting Her2
      expressing tumors.
AB  - In this study, we describe the synthesis and characterization of a conjugate
      consisting of poly(ethylene glycol 2,000 Da)(10)-graft-poly(ethylene imine 25
      kDa) (PEG-PEI) covalently coupled to Trastuzumab (Herceptin) via N-succinimidyl-3
      (2-pyridyldithio)propionate (SPDP) for specific gene delivery to Her2-expressing
      cell lines. The efficiency of DNA condensation was studied using an ethidium
      bromide exclusion assay and demonstrated negligible differences compared to PEG
      PEI. Conjugate complex sizes were determined by dynamic light scattering to be in
      the range 130-180 nm. zeta potentials at different N/P ratios were close to
      neutral. Flow cytometry and confocal microscopy revealed efficient binding and
      uptake of Trastuzumab-PEI-PEG complexes using Her2-positive SK-BR-3 cells. In
      contrast, binding and uptake into Her2-negative OVCAR-3 cells was negligible. In
      good correlation with these findings, reporter gene expression using targeted
      complexes in SK-BR-3 cells was up to sevenfold higher than that of unmodified PEG
      PEI complexes. With the use OVCAR-3 cells, no significant difference in
      expression efficiencies could be observed between conjugate and PEG-PEI
      complexes. Inhibition experiments with free Trastuzumab showed a significant
      decrease in reporter gene expression using SK-BR-3 cells but no decrease using
      OVCAR-3 cells, strongly supporting a specific Her2-receptor-mediated uptake
      mechanism. Our results suggest that Trastuzumab-PEI-PEG might be a promising new
      bioconjugate for targeted gene transfer to Her2-positive tumor cells in vivo.

PMID- 16984129
TI  - Design, synthesis, and evaluation of enhanced DNA binding new lipopolythioureas.
AB  - Nonviral gene delivery is limited to a large extent by the cationic nature of
      most of the chemical vector. We have shown that lipopolythioureas interact with
      DNA. However, lipopolythioureas were not very efficient at transfecting cells,
      probably due to reduced interaction between the noncationic synthetic lipid and
      the cell membrane. Here, we report that liposomes made from a new thiourea lipid,
      DPPC, and a lipid bearing an RGD ligand allowed very efficient entry of the
      lipopolythioureas into integrin alpha(v)beta(3) expressing cells. In addition, we
      show that a stable interaction between DNA and lipopolythiourea could be obtain
      with two thiourea groups. Moreover, the addition of a hydrophilic terminus
      improves the formulation of these new DNA binding agents.

PMID- 16984130
TI  - Influence of polyethylene glycol chain length on the physicochemical and
      biological properties of poly(ethylene imine)-graft-poly(ethylene glycol) block
      copolymer/SiRNA polyplexes.
AB  - Polyplexes between siRNA and poly(ethylene imine) (PEI) derivatives are promising
      nonviral carriers for siRNA. The polyplex stability is of critical importance for
      efficient siRNA delivery to the cytoplasm. Here, we investigate the effect of
      PEGylation at a constant ratio ( approximately 50%) on the biophysical properties
      of the polyplexes. Particle size, zeta potential, and stability against heparin
      as well as RNase digestion and reporter gene knockdown under in vitro conditions
      of different siRNA polyplexes were characterized. Stability and size of siRNA
      polyplexes were clearly influenced by PEI-PEG structure, and high degrees of
      substitution such as PEI(25k)-g-PEG(550)(30) resulted in large (300-400 nm),
      diffuse complexes (AFM) which showed condensation behavior only at high N/P
      ratios. All other polyplexes and the PEI control showed similar sizes (150 nm)
      and compact structures in AFM, with complete condensation reached at N/P ratio of
      3. Stability of siRNA polyplexes against heparin displacement and RNase digestion
      could be modified by PEGylation. Protection against RNase digestion was highest
      for PEI(25k)-g-PEG(5k)(4) and PEI(25k)-g-PEG(20k)(1), while siRNA/PEI provided
      insufficient protection. In knockdown experiments using NIH/3T3 fibroblasts
      stably expressing beta-galactosidase, it was shown that PEG chain length had a
      significant influence on biological activity of siRNA. Polyplexes with siRNA
      containing PEI(25k)-g-PEG(5k)(4) and PEI(25k)-g-PEG(20k)(1) yielded similar
      efficiencies of ca. 70% knockdown as lipofectamine controls. Confocal microscopy
      demonstrated enhanced cellular uptake of siRNA into cytosol by polyplexes
      formation with PEI copolymers. In conclusion, both the chain length and graft
      density of PEG were found to strongly influence siRNA condensation and stability
      and hence affect the knockdown efficiency of PEI-PEG/siRNA polyplexes.

PMID- 16984131
TI  - Synthesis of a new water-soluble rhodamine derivative and application to protein
      labeling and intracellular imaging.
AB  - Synthesis of a new fluorescent rhodamine derivative, dye 1, is reported. This
      probe is different from other rhodamines insofar as it has several (four)
      carboxylic acid functionalities to promote water solubility and facilitate
      conjugation to proteins. It also has an aryl bromide functionality that could, in
      principle, be used to further functionalize the system for specialized
      applications. Dye 1 was conjugated to a model protein called ACBP (acyl-CoA
      binding protein). The properties of this conjugate were tested to establish that
      the label does not significantly perturb the binding function of the protein to
      its natural ligand in vitro and to confirm that its secondary structure was not
      significantly perturbed (circular dichroism). Experiments were performed to test
      if the labeled protein could be imported into living COS-7 cells (using the
      Chariot-peptide delivery system) and, if so, to observe, via fluorescence
      microscopy, which of the labeled protein was able to migrate to the nucleus, as
      expected for ACBP in cells. In the event, all these postulates were confirmed.

PMID- 16984132
TI  - Synthesis and biological evaluation of EC140: a novel folate-targeted vinca
      alkaloid conjugate.
AB  - A novel folate conjugate of desacetylvinblastine monohydrazide (DAVLBH), herein
      referred to as EC140, was designed and evaluated for biological activity against
      folate receptor (FR)-positive cells and tumors. EC140 was produced by coupling a
      peptidic analogue of the vitamin folic acid to DAVLBH via an acylhydrazone bond.
      This water-soluble conjugate was found to retain high affinity for FR-positive
      cells, and it produced specific, dose-responsive activity in vitro. Initial in
      vivo tests confirmed EC140's activity in both syngeneic and xenograft models.
      Hence, enduring complete responses were observed in animals bearing established,
      subcutaneous tumors prior to therapy using regimens that produced minor toxicity.
      In contrast, treatment with the unconjugated DAVLBH drug produced nominal
      efficacy when dosed at its MTD. Overall, EC140's performance in vitro and in vivo
      warrants further preclinical study before this novel targeted chemotherapeutic is
      considered for clinical investigation.

PMID- 16984134
TI  - Hemoglobin vesicles containing methemoglobin and L-tyrosine to suppress
      methemoglobin formation in vitro and in vivo.
AB  - Hemoglobin (Hb) vesicles have been developed as cellular-type Hb-based O(2)
      carriers in which a purified and concentrated Hb solution is encapsulated with a
      phospholipid bilayer membrane. Ferrous Hb molecules within an Hb vesicle were
      converted to ferric metHb by reacting with reactive oxygen species such as
      hydrogen peroxide (H(2)O(2)) generated in the living body or during the
      autoxidation of oxyHb in the Hb vesicle, and this leads to the loss of O(2)
      binding ability. The prevention of metHb formation by H(2)O(2) in the Hb vesicle
      is required to prolong the in vivo O(2) carrying ability. We found that a mixed
      solution of metHb and L-tyrosine (L-Tyr) showed an effective H(2)O(2) elimination
      ability by utilizing the reverse peroxidase activity of metHb with L-Tyr as an
      electron donor. The time taken for the conversion of half of oxyHb to metHb
      (T(50)) was 420 min for the Hb vesicles containing 4 g/dL (620 microM) metHb and
      8.5 mM L-Tyr ((metHb/L-Tyr) Hb vesicles), whereas the time of conversion for the
      conventional Hb vesicles was 25 min by stepwise injection of H(2)O(2) (310
      microM) in 10 min intervals. Furthermore, in the (metHb/L-Tyr) Hb vesicles, the
      metHb percentage did not reach 50% even after 48 h under a pO(2) of 40 Torr at 37
      degrees C, whereas T(50) of the conventional Hb vesicles was 13 h under the same
      conditions. Moreover, the T(50) values of the conventional Hb vesicles and the
      (metHb/L-Tyr) Hb vesicles were 14 and 44 h, respectively, after injection into
      rats (20 mL/kg), confirming the remarkable inhibitory effect of metHb formation
      in vivo in the (metHb/L-Tyr) Hb vesicles.

PMID- 16984133
TI  - Reducible poly(amido ethylenimine)s designed for triggered intracellular gene
      delivery.
AB  - Poly(amido ethylenimine) polymers, a new type of peptidomimetic polymer,
      containing multiple disulfide bonds (SS-PAEIs) designed to degrade after delivery
      of plasmid DNA (pDNA) into the cell were synthesized and investigated as new
      carriers for triggered intracellular gene delivery. More specifically, three SS
      PAEIs were synthesized from Michael addition reactions between cystamine
      bisacrylamide (CBA) and three different ethylene amine monomers, i.e.,
      ethylenediamine (EDA), diethylenetriamine (DETA), or triethylenetetramine (TETA).
      Complete addition reactions were confirmed by (1)H NMR. The molecular weight,
      buffer capacity, and relative degree of branching for each SS-PAEI was determined
      by gel permeation chromatography (GPC), acid-base titration, and liquid
      chromatography-mass spectroscopy (LC-MS), respectively. Physicochemical
      characteristics of polymer/pDNA complexes (polyplexes) were analyzed by gel
      electrophoresis, particle size, and zeta-potential measurements. All three SS
      PAEIs effectively complex pDNA to form nanoparticles with diameters less than 200
      nm and positive surface charges of approximately 32 mV. The in vitro gene
      transfer properties of SS-PAEIs were evaluated using mouse embryonic fibroblast
      cell (NIH3T3), primary bovine aortic endothelial cell (BAEC), and rat aortic
      smooth muscle cell (A7R5) lines. Interestingly, polyplexes based on all three SS
      PAEIs exhibited remarkably high levels of reporter gene expression with nearly
      20x higher transfection efficiency than polyethylenimine 25k. The high
      transfection efficiency was maintained in the presence of 10% serum in the
      transfection medium. Furthermore, confocal microscopy experiments using labeled
      pDNA indicated that polyplexes of SS-PAEI displayed greater intracellular
      distribution of pDNA as compared to PEI, most likely due to environmentally
      triggered release. Therefore, SS-PAEIs are a new class of transfection agents
      that facilitate high gene expression while maintaining a low level of toxicity.

PMID- 16984135
TI  - Delivery of the p38 MAPkinase inhibitor SB202190 to angiogenic endothelial cells:
      development of novel RGD-equipped and PEGylated drug-albumin conjugates using
      platinum(II)-based drug linker technology.
AB  - Endothelial cells play an important role in inflammatory disorders, as they
      control the recruitment of leukocytes into inflamed tissue and the formation of
      new blood vessels. Activation of p38MAP kinase results in the production of
      proinflammatory cytokines and the expression of adhesion molecules. P38MAP kinase
      inhibitors are therefore considered important candidates for the treatment of
      inflammatory disorders. In the present study, we propose a novel strategy to
      counteract these processes by delivery of the p38MAP kinase inhibitor SB202190
      into angiogenic endothelial cells. A drug-targeting conjugate was developed by
      conjugation of SB202190 to human serum albumin (HSA) using a novel platinum-based
      linker. Specificity for angiogenic endothelial cells was introduced by
      conjugation of cyclic RGD-peptides via bifunctional polyethylene glycol linkers.
      The final products contained an average of nine SB202190 and six RGDPEG groups
      per albumin. The platinum-based linker displayed high stability in buffers and
      culture medium, but released SB202190 slowly upon competition with sulfur
      containing ligands like glutathione. RGDPEG-SB-HSA bound to alpha(v3)-integrin
      expressing endothelial cells (human umbilical cord vein endothelial cells) with
      low nanomolar affinity and was subsequently internalized. When HUVEC were treated
      with TNF to induce inflammatory events, pretreatment with RGDPEG-SB-HSA partially
      inhibited proinflammatory gene expression (IL-8, E-selectin; 30% inhibition) and
      secretion of cytokines (IL-8, 34% inhibition). We conclude that the developed
      RGDPEG-SB-HSA conjugates provide a novel means to counteract inflammation
      disorders such as rheumatoid arthritis.

PMID- 16984136
TI  - Design and synthesis of ferrocene probe molecules for detection by
      electrochemical methods.
AB  - A series of ferrocenyl conjugates to fatty acids have been designed and
      synthesized to establish the key properties required for use in biomolecular
      binding studies. Amperometric detection of the ferrocene conjugates was sought in
      the region of 0.3 V (vs Ag/AgCl) for use in protein/blood solutions. Different
      linkers and solubilizing moieties were incorporated to produce a conjugate with
      optimal electrochemical properties. In electrochemical studies, the linker
      directly attached to the ferrocene was found to affect significantly the E(1/2)
      value and the stability of the ferrocenium cation. Ester-linked ferrocene
      conjugates had E(1/2) ranging from +400 to +410 mV, while amide-linked compounds
      ranged from +350 to +370 mV and the amines +260 to +270 mV. Folding of long-chain
      substituents around the ferrocene, also significantly affected by the choice of
      linker, was inferred as a secondary effect that increased E(1/2). The stability
      of the ferrocenium cation decreased systematically as E(1/2) increased.
      Disubstituted ferrocene ester and amide conjugates, with oxidation potentials of
      +640 and +570 mV, respectively, showed only a barely discernible reduction wave
      in cyclic voltammetry at 50 mV/s. Electrochemical measurements identified two
      lead compounds with the common structural characteristics of an amide and
      carbamate linker (compounds 17 and 21) with a C(11) fatty acid chain attached. It
      is envisaged that such molecules can be used to mimic and study the biomolecular
      binding interaction between fatty acids and molecules such as human serum
      albumin.

PMID- 16984137
TI  - Synthesis of potent inhibitors of anthrax toxin based on poly-L-glutamic acid.
AB  - We report the synthesis of biodegradable polyvalent inhibitors of anthrax toxin
      based on poly-L-glutamic acid (PLGA). These biocompatible polyvalent inhibitors
      are at least 4 orders of magnitude more potent than the corresponding monovalent
      peptides in vitro and are comparable in potency to polyacrylamide-based
      inhibitors of anthrax toxin assembly. We have elucidated the influence of peptide
      density on inhibitory potency and demonstrated that these inhibitory potencies
      are limited by kinetics, with even higher activities seen when the inhibitors are
      preincubated with the heptameric receptor-binding subunit of anthrax toxin prior
      to exposure to cells. These polyvalent inhibitors are also effective at
      neutralizing anthrax toxin in vivo and represent attractive leads for designing
      biocompatible anthrax therapeutics.

PMID- 16984138
TI  - Synthesis and characterization of AP5346, a novel polymer-linked
      diaminocyclohexyl platinum chemotherapeutic agent.
AB  - Syntheses of the novel polymer-bound platinum-based chemotherapeutic agent
      poly(HPMA)-GGG-Ama=Pt=(1R,2R)-DACH, AP5346, and its precursors are reported. The
      method utilized in preclinical development of AP5346 is described herein.
      Additionally, an improved synthesis, which has shown that ion exchange resins can
      be removed, significantly less platinum can be used when the reaction mixture is
      pH-stated, and the synthesis can be performed at a higher concentration, is
      reported. These combined improvements result in a more cost-effective, scaleable
      procedure. Various methods of analysis of the drug substance are also discussed.
      Specifically, (1)H NMR spectroscopy is used for identity and can also distinguish
      small molecule impurities to below 0.1%. (195)Pt NMR determines the coordination
      environment of the platinum and also identity and purity in relation to platinum
      chelation of the construct. Size exclusion chromatography is used to establish
      the molecular weight of AP5346 while ICP-AES determines platinum content and
      platinum release rates in phosphate-buffered saline. The cumulative results of
      this work have yielded an efficient syntheses of a polymer-based chemotherapeutic
      agent with subsequent detailed characterization methods.

PMID- 16984139
TI  - HIV-1 Tat peptide immunoconjugates differentially sensitize breast cancer cells
      to selected antiproliferative agents that induce the cyclin-dependent kinase
      inhibitor p21WAF-1/CIP-1.
AB  - In this study, we evaluated the ability of anti-p21 antibodies conjugated to 17
      mer peptides [GRKKRRQRRRPPQGYGC] harboring the membrane-translocating and nuclear
      import sequences [underlined] of HIV-1 tat protein to inhibit the cyclin
      dependent kinase inhibitor, p21(WAF-1/Cip-1) (p21) and differentially sensitize
      MDA-MB-468 and MCF-7 human breast cancer (BC) cells to the antiproliferative
      effects of treatments that induce or do not induce p21. BC cells were treated
      with increasing concentrations of epidermal growth factor (EGF; 0.5-10 nM), the
      topoisomerase I inhibitor, camptothecin (CPT; 0.1-4 muM), or increasing doses of
      gamma-radiation (2-20 Gy). Western blot was used to evaluate p21 expression. The
      effect of treatment on cell cycle distribution was studied. Growth inhibition was
      measured by the WST-1 assay. Expression of p21 was increased in MDA-MB-468 cells
      treated with EGF or CPT but not by gamma-irradiation. MCF-7 cells exhibited p21
      upregulation following exposure to CPT and gamma-radiation but not EGF. EGF
      caused cell cycle arrest in G(1) phase for MDA-MB-468 cells. CPT caused G(1)
      phase arrest in MDA-MB-468 cells and prolonged S phase in MCF-7 cells. gamma
      Radiation caused an increase in cells in G(2)/M phase for MDA-MB-468 and MCF-7.
      MDA-MB-468 cells were growth-inhibited by EGF, CPT, and gamma-radiation. MCF-7
      cells were growth-stimulated by EGF and inhibited by CPT and gamma-radiation.
      Combining EGF with tat-anti-p21 immunoconjugates (ICs) amplified the growth
      inhibitory effect on MDA-MB-468 cells 1.2-fold to 2.3-fold, but had no effect on
      the growth stimulation of MCF-7 cells by EGF. Tat-anti-p21 ICs sensitized MCF-7
      cells 1.4-fold to gamma-radiation but had no effect on the growth of gamma
      irradiated MDA-MB-468 cells. Tat-anti-p21 ICs sensitized both MDA-MB-468 and MCF
      7 cells 1.7-fold to CPT. We conclude that tat-anti-p21 ICs are promising
      sensitizers for cytotoxic cancer therapies and that their sensitization is
      dependent on treatment-related p21 expression. This general approach could
      potentially be extended to other growth-regulatory molecules that are associated
      with tumor growth and progression.

PMID- 16984140
TI  - A method to optimize PEG-coating of red blood cells.
AB  - Alloimmunization to donor blood group antigens remains a significant problem in
      transfusion medicine. A proposed method to overcome donor-recipient blood group
      incompatibility is to mask the blood group antigens by the covalent attachment of
      poly(ethylene glycol) (PEG) to the red blood cell (RBC) membrane. Despite much
      work in the development of PEG-coating of RBCs, there is a paucity of data on the
      optimization of the PEG-coating technique; it is the aim of this study to
      determine the optimum conditions for PEG coating using a cyanuric chloride
      reactive derivative of methoxy-PEG as a model polymer. Activated PEG of molecular
      mass 5 kDa was covalently attached to human RBCs under various reaction
      conditions. Inhibition of binding of a blood-type specific antiserum (anti-D) was
      employed to evaluate the effect of the PEG-coating, quantified by hemocytometry
      and flow-cytometry. RBC morphology was examined by light and scanning electron
      microscopy. Statistical analysis of experimental design together with microscopy
      results showed that the optimum PEGylation conditions are pH = 8.7, temperature =
      14 degrees C, and reaction time = 30 min. An optimum concentration of reactive
      PEG could not be determined. At high polymer concentrations (>25 mg/mL) a
      predominance of type III echinocytes was observed, and as a result, a
      concentration of 15 mg/mL is the highest recommended concentration for a linear
      PEG of molecular mass 5 kDa.

PMID- 16984142
TI  - Transferrin-loaded nido-carborane liposomes: tumor-targeting boron delivery
      system for neutron capture therapy.
AB  - The nido-carborane lipid 2 as a double-tailed boron lipid was synthesized from
      heptadecanol in five steps. The lipid 2 formed stable liposomes at 25% molar
      ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the
      surface of boron liposomes (Tf(+)-PEG-CL liposomes) by the coupling of
      transferrin to the PEG-CO(2)H moieties of Tf(-)-PEG-CL liposomes. The
      biodistribution of Tf(+)-PEG-CL liposomes, in which (125)I-tyraminyl inulins were
      encapsulated, showed that Tf(+)-PEG-CL liposomes accumulated in tumor tissues and
      stayed there for a sufficiently long time to increase tumor/blood concentration
      ratio, although Tf(-)-PEG-CL liposomes were gradually released from tumor tissues
      with time. A boron concentration of 22 ppm in tumor tissues was achieved by the
      injection of Tf(+)-PEG-CL liposomes at 7.2 mg/kg body weight boron in tumor
      bearing mice. After neutron irradiation, the average survival rate of mice not
      treated with Tf(+)-PEG-CL liposomes was 21 days, whereas that of the treated mice
      was 31 days. Longer survival rates were observed in the mice treated with Tf(+)
      PEG-CL liposomes; one of them even survived for 52 days after BNCT.

PMID- 16984141
TI  - Structure-activity relationships of 111In- and 99mTc-labeled quinolin-4-one
      peptidomimetics as ligands for the vitronectin receptor: potential tumor imaging
      agents.
AB  - The integrin receptor alpha(v)beta(3) is overexpressed on the endothelial cells
      of growing tumors and on some tumor cells themselves. Radiolabeled
      alpha(v)beta(3) antagonists have demonstrated potential application as tumor
      imaging agents and as radiotherapeutic agents. This report describes the total
      synthesis of eight new HYNIC and DOTA conjugates of receptor alpha(v)beta(3)
      antagonists belonging to the quinolin-4-one class of peptidomimetics, and their
      radiolabeling with (99m)Tc (for HYNIC) and (111)In (for DOTA). Tethering of the
      radionuclide-chelator complexes was achieved at two different sites on the
      quinolin-4-one molecule. All such derivatives maintained high affinity for
      receptor alpha(v)beta(3) and high selectivity versus receptors alpha(IIb)beta(3),
      alpha(v)beta(5), alpha(5)beta(1). Biodistribution of the radiolabeled compounds
      was evaluated in the c-neu Oncomouse mammary adenocarcinoma model. DOTA conjugate
      (111)In-TA138 presented the best biodistribution profile. Tumor uptake at 2 h
      postinjection was 9.39% of injected dose/g of tissue (%ID/g). Activity levels in
      selected organs was as follows: blood, 0.54% ID/g; liver, 1.94% ID/g; kidney,
      2.33% ID/g; lung, 2.74% ID/g; bone, 1.56% ID/g. A complete biodistribution
      analysis of (111)In-TA138 and the other radiolabeled compounds of this study are
      presented and discussed. A scintigraphic imaging study with (111)In-TA138 showed
      a clear delineation of the tumors and rapid clearance of activity from nontarget
      tissues.

PMID- 16984144
TI  - Chemical conjugate TMV-peptide bivalent fusion vaccines improve cellular immunity
      and tumor protection.
AB  - Chemical conjugation of CTL peptides to tobacco mosaic virus (TMV) has shown
      promise as a molecular adjuvant scaffold for augmentation of cellular immune
      responses to peptide vaccines. This study demonstrates the ease of generating
      complex multipeptide vaccine formulations using chemical conjugation to TMV for
      improved vaccine efficacy. We have tested a model foreign antigen target-the
      chicken ovalbumin-derived CTL peptide (Ova peptide), as well as mouse melanoma
      associated CTL epitopes p15e and tyrosinase-related protein 2 (Trp2) peptides
      that are self-antigen targets. Ova peptide fusions to TMV, as bivalent
      formulations with peptides encoding additional T-help or cellular uptake via the
      integrin-receptor binding RGD peptide, showed improved vaccine potency evidenced
      by significantly enhanced numbers of antigen-reactive T cells measured by in
      vitro IFNgamma cellular analysis. We measured the biologically relevant outcome
      of vaccination in protection of mice from EG.7-Ova tumor challenge, which was
      achieved with only two doses of vaccine ( approximately 600 ng peptide) given
      without adjuvant. The p15e peptide alone or Trp2 peptide alone, or as a bivalent
      formulation with T-help or RGD uptake epitopes, was unable to stimulate effective
      tumor protection. However, a vaccine with both CTL peptides fused together onto
      TMV generated significantly improved survival. Interestingly, different bivalent
      vaccine formulations were required to improve vaccine efficacy for Ova or
      melanoma tumor model systems.

PMID- 16984143
TI  - Carbohydrate-appended 3-hydroxy-4-pyridinone complexes of the [M(CO)3]+ core (M =
      Re, 99mTc, 186Re).
AB  - This work describes the use of 3-hydroxy-4-pyridinone ligands for binding the
      [M(CO)(3)](+) core (M = Re, Tc) in the context of preparing novel Tc(I) and Re(I)
      glucose conjugates. Five pyridinone ligands bearing pendent carbohydrate
      moieties, HL(1-5), were coordinated to the [M(CO)(3)](+) core on the macroscopic
      scale (M = Re) and on the tracer scale (M = (99m)Tc, (186)Re). On the macroscopic
      scale the complexes, ReL(1-5)(CO)(3)(H(2)O), were thoroughly characterized by
      mass spectrometry, IR spectroscopy, UV-visible spectroscopy, elemental analysis,
      and 1D/2D NMR spectroscopy. Characterization confirmed the bidentate coordination
      of the pyridinone and the pendent nature of the carbohydrate and suggests the
      presence of a water molecule in the sixth coordination site. In preliminary
      biological evaluation, both the ligands and complexes were assessed as potential
      substrates or inhibitors of hexokinase, but showed no activity. Labeling via the
      [(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor gave the tracer species (99m)TcL(1
      5)(CO)(3)(H(2)O) in high radiochemical yields. Similar high radiochemical yields
      when labeling with (186)Re were facilitated by in situ preparation of the
      [(186)Re(CO)(3)(H(2)O)(3)](+) species in the presence of HL(1-5) to give
      (186)ReL(1-5)(CO)(3)(H(2)O). Stability challenges, incubating (99m)TcL(1
      5)(CO)(3)(H(2)O) in the presence of excess cysteine and histidine, confirmed
      complex stability up to 24 h.

PMID- 16984145
TI  - Gene carriers based on hexanediol diacrylate linked oligoethylenimine: effect of
      chemical structure of polymer on biological properties.
AB  - Two biodegradable polycations based on hexanediol diacrylate linked
      oligoethylenimine (OEI) were synthesized by applying different reaction
      temperatures, 20 degrees C (LT-OEI-HD) and 60 degrees C (HT-OEI-HD). Their
      structural properties were analyzed by NMR, FTIR, and SEC/MALLS (size exclusion
      chromatography coupled with multiangle laser light scattering detection).
      Reaction temperature strongly influenced molecular weight and ester/amide ratio
      and thus resulted in polycations with different biological activities and
      degradation profiles. LT-OEI-HD was an ester-based polycation of 8.7 kDa which
      degraded rapidly at pH 7 and pH 9 respectively. HT-OEI-HD had a molecular weight
      of 26.6 kDa, was mainly based on amides, and degraded more slowly than LT-OEI-HD.
      Both polymers mediated gene transfer as efficiently as linear polyethylenimine of
      22 kDa in two cell lines while being less toxic at their optimal
      conjugate/plasmid (C/P) ratios. LT-OEI-HD needed higher C/P ratios for gene
      delivery; however, it was significantly less toxic than HT-OEI-HD.

PMID- 16984146
TI  - Synthesis and characterization of immunogens based on calix[4]arene-crown-6 for
      the generation of antibodies directed towards cesium ions.
AB  - With the aim of generating antibodies directed towards cesium, a calix[4]arene
      crown-6 in the 1,3-alternate conformation bearing an N-hydroxysuccinimide
      function was synthesized. The calixarene was coupled to bovine serum albumin
      using different calixarene/protein ratios, and cesium was loaded. Conjugates were
      characterized using trinitrobenzenesulfonic acid derivatization, matrix assisted
      laser desorption ionisation-mass spectrometry (MALDI-TOF-MS), and inductively
      coupled plasma-mass spectrometry (ICP-MS). Targeted lysines were determined after
      enzymatic cleavage followed by MALDI-TOF-MS, and a progressive targeting related
      to lysines accessibility was observed.

PMID- 16984147
TI  - Directing quadruplex-stabilizing drugs to the telomere: synthesis and properties
      of acridine-oligonucleotide conjugates.
AB  - Conjugates containing quadruplex-stabilizing acridines linked to oligonucleotides
      that are complementary to the G-rich human telomere sequence were synthesized.
      Acylation of 3,6-diaminoacridine followed by two Michael reactions provided
      derivatives suitable for conjugation, which were coupled to resin-linked amine
      modified oligonucleotides by activating the carboxyl group with pentafluorophenyl
      4-nitrobenzenesulfonate. After deprotection with aqueous ammonia at room
      temperature, conjugates incorporating different acridines, linkers, and
      oligonucleotide sequences were obtained. These were tested for their ability to
      stabilize intramolecular DNA quadruplexes that are based on the human telomeric
      repeat sequence (GGGTTA)(n).

PMID- 16984148
TI  - Efficient synthesis of an aldehyde functionalized hyaluronic acid and its
      application in the preparation of hyaluronan-lipid conjugates.
AB  - An efficient method to synthesize hyaluronan oligosaccharide lipid conjugates is
      described. This strategy is based on the introduction of a double bond in the
      glucuronic acid of the hyaluronic acid (HA), by the biodegradation of HA with
      hyaluronate lyase, followed by the generation of a free aldehyde group at the
      nonreducing end of hyaluronic acid via ozonolysis and the subsequent reduction of
      the generated ozonide. The resulting aldehyde-functionalized HA is then coupled
      to dipalmitoyl phosphatidylethanolamine (DPPE) using reductive amination
      chemistry. This methodology can be extended to link molecules such as biotin,
      polymers, or proteins to HA for numerous applications in drug delivery and in the
      creation of biocompatible materials for tissue repair and engineering.

PMID- 16984150
TI  - New application of AAO template: a mold for nanoring and nanocone arrays.
AB  - Nanoring and nanocone arrays were prepared by conical openings of nanopores in as
      prepared AAO film as a mold.

PMID- 16984149
TI  - An intramolecular cyclization reaction is responsible for the in vivo inefficacy
      and apparent pH insensitive hydrolysis kinetics of hydrazone carboxylate
      derivatives of doxorubicin.
AB  - Contradictory reports concerning the pH sensitive hydrolysis kinetics of certain
      hydrazone carboxylates of doxorubicin have appeared in this journal (Kaneko et
      al., Bioconjugate Chem. 1991, 2, 133. Padilla De Jesus et al., Bioconjugate Chem.
      2002, 13, 453). Since the pH stability of the drug-carrier linkage in
      macromolecular prodrugs has a significant bearing on pharmacological efficacy,
      the hydrolysis kinetics of low molecular weight and polymeric doxorubicin
      hydrazone carboxylates were therefore reinvestigated. As observed previously, the
      conjugates readily release native doxorubicin at pH 5. Unexpectedly, in neutral
      buffer the hydrazone carboxylate conjugates do not release native doxorubicin,
      but instead rapidly release a doxorubicin derivative substituted at C-9 by 3,6
      dihydro-1,3,4-oxadiazin-2-one with first-order kinetics (t(1/2) = 2.5 h). The
      proposed intramolecular cyclization reaction involving doxorubicin's C-14
      hydroxyl and the carboxylate-substituted hydrazone rationalizes the seemingly
      anomalous hydrolysis kinetics seen for hydrazone carboxylate linked doxorubicin,
      and provides a possible explanation for the poor antitumor activity exhibited by
      polymer-doxorubicin conjugates utilizing this specific type of linkage.

PMID- 16984151
TI  - Protein side-chain dynamics observed by solution- and solid-state NMR:
      comparative analysis of methyl 2H relaxation data.
AB  - Rapid advances in solid-state MAS NMR made it possible to probe protein dynamics
      on a per-residue basis, similar to solution experiments. In this work we compare
      methyl 2H relaxation rates measured in the solid and liquid samples of alpha
      spectrin SH3 domain. The solution data are treated using a model-free approach to
      separate the contributions from the overall molecular tumbling and fast internal
      motion. The latter part forms the basis for comparison with the solid-state data.
      Although the accuracy of solid-state measurements is limited by deuterium spin
      diffusion, the results suggest a significant similarity between methyl dynamics
      in the two samples. This is a potentially important observation, preparing the
      ground for combined analysis of the dynamics data by solid- and solution-state
      NMR.

PMID- 16984152
TI  - Synthesis of RNA using 2'-O-DTM protection.
AB  - tert-Butyldithiomethyl (DTM), a novel hydroxyl protecting group, cleavable under
      reductive conditions, was developed and applied for the protection of 2'-OH
      during solid-phase RNA synthesis. This function is compatible with all standard
      protecting groups used in oligonucleotide synthesis, and allows for fast and high
      yield synthesis of RNA. Oligonucleotides containing the 2'-O-DTM groups can be
      easily deprotected under the mildest possible aqueous and homogeneous conditions.
      The preserved 5'-O-DMTr function can be used for high-throughput cartridge RNA
      purification.

PMID- 16984153
TI  - Preparation and characterization of conducting trimetallic nickel-dithiolene
      complexes with bridging tetrathiooxalate ligands.
AB  - Trimetallic nickel dithiolene complexes with two tetrathiooxalate (tto) ligands
      were obtained by a reaction monitored by ESI-mass spectrometry followed by HPLC
      separation and were characterized by elemental or crystal structural analysis, MO
      calculations, and electrical conductivity measurements.

PMID- 16984154
TI  - DFTMP, an NMR reagent for assessing the near-neutral pH of biological samples.
AB  - A new NMR chemical shift standard and pH indicator,
      difluorotrimethylsilanylphosphonic acid (DFTMP), is described, and the utility of
      this reagent is demonstrated for in situ determination of pH in complex
      biofluids. The pH dependence of this reagent allows accurate in situ
      determination of aqueous solution pH to within an RMSE of 0.02 pH units over a pH
      range of 5 to 8. Advantages of this reagent over previously described pH
      sensitive components include (1) lack of metal binding affinity, (2) minimal
      disturbance of endogenous spectral regions, and (3) the potential to function as
      a multinuclear pH indicator and chemical shift reference point for 19F, 1H, and
      31P nuclei. This reagent will be generally useful for NMR experiments on
      biological systems where the pH needs to be accurately measured at the moment of
      data acquisition.

PMID- 16984155
TI  - From carbon dioxide to methane: homogeneous reduction of carbon dioxide with
      hydrosilanes catalyzed by zirconium-borane complexes.
AB  - A mixture of a zirconium benzyl phenoxide complex and
      tris(pentafluorophenyl)borane is reported that catalyzes the hydrosilation
      reaction of carbon dioxide to generate methane via a bis(silyl)acetal
      intermediate.

PMID- 16984156
TI  - Chemical tuning of positive and negative magnetoresistances, and
      superconductivity in 1222-type ruthenocuprates.
AB  - A remarkable variety of conducting states has been found in RuSr2(R2-xCex)Cu2O10
      delta ruthenocuprates by tuning the properties of the magnetic CuO2 and RuO2
      layers through small changes in the chemistry of the (R,Ce)2O2-delta slab. Both
      the R3+ cation size and the charge transfer determined by the R/Ce ratio and the
      oxygen deficiency delta are important controlling parameters that tune ground
      state properties from positive magnetoresistive to negative magnetoresistive to
      superconducting.

PMID- 16984157
TI  - Catalytic one-pot synthesis of cyclic amidines by virtue of tandem reactions
      involving intramolecular hydroamination under mild conditions.
AB  - A new synthetic methodology for the generation of cyclic amidines has been
      developed by the reaction of 1,n-aminoalkynes with electron-deficient azides
      using a ruthenium catalyst at ambient temperature. The reaction proceeds most
      likely via a tandem sequence of intramolecular hydroamination of aminoalkynes,
      cycloaddition of azides with the resulting enamines, and rearrangement of
      triazoline intermediates. It demonstrates, as the proof-of-principle, that an
      equilibria cascade sequence can be favorably driven by an irreversible step, thus
      enabling a facile one-pot synthetic route to deliver molecular complexity under
      unprecedented mild conditions without relying on the traditional linear
      approaches.

PMID- 16984158
TI  - The [1,5]-Brook rearrangement: an initial application in anion relay chemistry.
AB  - The [1,5]-Brook rearrangement proceeds efficiently in a series of hydroxyl
      dithiane substrates with sodium and potassium bases; less effective are lithium
      bases. That the mode of silyl migration is intramolecular was demonstrated by a
      crossover experiment. Finally, the tricomponent anion relay chemistry (ARC)
      coupling tactic was demonstrated employing the [1,5]-Brook rearrangement.

PMID- 16984159
TI  - Enantioselective rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates
      and terminal alkynes: application to the total synthesis of (+)-lasubine II.
AB  - The use of TADDOL-based phosphoramidite ligands on rhodium allows for the
      incorporation of terminal alkynes in the [2+2+2] cycloaddition with alkenyl
      isocyanates. Terminal aliphatic alkynes provide bicyclic lactams, while the use
      of aryl alkynes provides complementary access to vinylogous amides. Product
      selectivity seems to be governed by a combination of electronics and sterics,
      with smaller and/or more electron-deficient substituents favoring lactam
      formation. The use of homologous alkenyl isocyanates leads to an expedient
      asymmetric total synthesis of the alkaloid lasubine II.

PMID- 16984160
TI  - Reductive DNA cleavage induced by UVA photoirradiation of NADH without oxygen.
AB  - UVA irradiation of dihydronicotinamide coenzyme (NADH), which plays a key role in
      a number of biological redox processes, results in effective DNA cleavage without
      oxygen via photoionization of NADH and the subsequent reaction of hydrated
      electron with DNA as well as photoinduced electron transfer from NADH to DNA.

PMID- 16984161
TI  - Hydroxylamine as an oxygen nucleophile. Structure and reactivity of ammonia
      oxide.
AB  - Ammonia oxide is revealed as a stable molecule in a crystal structure and as a
      likely reactive species in many reactions of hydroxylamine.

PMID- 16984162
TI  - Rhenium-catalyzed insertion of aldehyde into a C-H bond: synthesis of
      isobenzofuran derivatives.
AB  - A rhenium complex, [ReBr(CO)3(thf)]2, catalyzed reactions of aromatic ketimines
      with aldehydes to give isobenzofuran derivatives in good to excellent yields. In
      contrast to ruthenium and rhodium catalysts, aldehydes, which are polar
      unsaturated molecules, inserted into the C-H bond after activation by the rhenium
      complex.

PMID- 16984163
TI  - Self-healing of surfactant surface micelles on millisecond time scales.
AB  - We study the dynamics of surfactant micelles at the solid-liquid interface using
      a new atomic force-microscopic imaging mode to visualize the nanometer-level
      structural features of the micelles and the picometer-level lattice of the
      substrate simultaneously. We find that defects created in a crystalline micellar
      array by the scanning probe tip self-heal flawlessly in less than 6 ms.

PMID- 16984164
TI  - Synthesis and biradicaloid character of doubly linked corrole dimers.
AB  - Directly linked corrole dimer 1, which has a planar cyclooctatetraene in its
      core, has been synthesized from 2-borylcorrole in excellent yield. 2,3-Dichloro
      5,6-dicyano-1,4-benzoquinone (DDQ) oxidation of 1 provides its oxidized form 4,
      which has two NH protons in each corrole core. Dicorrole 4 and its Zn(II) complex
      6 exhibit broad electronic absorption spectra, and magnetic measurement has
      revealed their biradicaloid character.

PMID- 16984165
TI  - Electrochemical proteolytic beacon for detection of matrix metalloproteinase
      activities.
AB  - This communication describes a novel method for detecting matrix
      metalloproteinase-7 activity using a peptide substrate labeled with a ferrocene
      reporter. The substrate serves as a selective "electrochemical proteolytic
      beacon" (EPB) for this metalloproteinase. The EPB is immobilized on a gold
      electrode surface to enable "on-off" electrochemical signaling capability for
      uncleaved and cleaved events. The EPB is efficiently and selectively cleaved by
      MMP-7 as measured by the rate of decrease in redox current of ferrocene. Direct
      transduction of a signal corresponding to peptide cleavage events into an
      electronic signal thus provides a simple, sensitive route for detecting the MMP
      activity. The new method allows for identification of the activity of MMP-7 in
      concentrations as low as 3.4 pM. The concept can be extended to design a multiple
      peptide substrate labeled with different electroactive reporters for assaying
      multiple MMPs activities.

PMID- 16984166
TI  - Controllable distribution of single molecules and peptides within oligomer
      template investigated by STM.
AB  - This communication provides a facile method for distributing and dispersing
      molecules within a molecular template. Using the self-assembled template of
      oligo(phenylene-ethynylene) (OPE), organic molecules such as coronene (COR) and
      biomolecules such as tripeptide are controllably distributed and dispersed within
      this molecular template on highly oriented pyrolytic graphite (HOPG) surfaces.
      COR molecules were controllably distributed into various regular arrays by simply
      adjusting the molecular molar ratio, while tripeptide molecules were uniformly
      positioned at the vacancies of the OPE template.

PMID- 16984167
TI  - A combined SAXS/WAXS/XAFS setup capable of observing concurrent changes across
      the nano-to-micrometer size range in inorganic solid crystallization processes.
AB  - A novel combined SAXS/WAXS/XAFS setup for studying the self-assembly processes
      occurring during the crystallization of porous materials, such as ZnAlPO-34, is
      described. In a single experiment, it has been possible to obtain congruent and
      time-resolved information on aggregation processes in the synthesis gel, the
      incorporation process of Zn2+ ions in the framework, and the formation of the
      crystalline material.

PMID- 16984168
TI  - Structure transition and swapping pattern of clathrate hydrates driven by
      external guest molecules.
AB  - We first report here that under strong surrounding gas of external CH4 guest
      molecules the sII and sH methane hydrates are structurally transformed to the
      crystalline framework of sI, leading to a favorable change of the lattice
      dimension of the host-guest networks. The high power decoupling 13C NMR and Raman
      spectroscopies were used to identify structure transitions of the mixed CH4 +
      C2H6 hydrates (sII) and hydrocarbons (methylcyclohexane, isopentane) + CH4
      hydrates (sH). The present findings might be expected to provide rational
      evidences regarding the preponderant occurrence of naturally occurring sI methane
      hydrates in marine sediments. More importantly, we note that the unique and cage
      specific swapping pattern of multiguests is expected to provide a new insight for
      better understanding the inclusion phenomena of clathrate materials.

PMID- 16984169
TI  - Rotational polymorphism in 2-naphthalenethiol SAMs on Au(111).
AB  - We evidence by STM that 2-naphthalenethiol self-assembled monolayers formed at
      the n-tetradecane/Au(111) interface coexist as two structural phases which both
      possess molecules into two different orientations (standing and lying). Such a
      rotational polymorphism is observed and understood at the molecular level for the
      first time.

PMID- 16984170
TI  - Intermetallic compounds with 1D infinite tunnels. Syntheses and structures of
      AAu4In2 (A = K, Rb).
AB  - Four intermetallic compounds KxRb1-xAu4In2 (x = 0-1) synthesized by high
      temperature solid-state reactions display 1D infinite tunnel constructions with
      Au-In frameworks. These compounds show small but different cation displacements
      in the tunnels and are also air and moisture inert at room temperature, even in
      concentrated HCl(aq).

PMID- 16984171
TI  - Rapid production of metal-organic frameworks via microwave-assisted solvothermal
      synthesis.
AB  - This paper describes a very rapid technique for the production of metal-organic
      frameworks (MOF). The method uses a conventional microwave to nucleate crystal
      growth. A MOF synthesis that used to take hours or days can now be completed in
      30 s to 2 min. The yield goes from approximately 30% to over 90%. Novel MOFs can
      be made, since the growth process is no longer dependent on the walls or dust
      particles for nucleation. Particle sizes have a narrower distribution. Further,
      the particle size can be controlled by varying the precursor concentration.

PMID- 16984172
TI  - Organic azide inhibitors of cysteine proteases.
AB  - Cysteine proteases are crucial regulatory enzymes in human physiology and
      disease. Inhibitors are usually designed with reactive electrophiles to
      covalently bond to the catalytic cysteinyl sulfur, and consequently they also
      indiscriminately interact with biological thiolates and other nucleophiles,
      leading to toxic side effects in vivo. Here we describe an alternative to using
      reactive electrophiles, demonstrating the use of a much less reactive
      azidomethylene substituent (-CH2-N3) that confers potent inhibition of cysteine
      proteases. This new approach resulted in potent, reversible, competitive
      inhibitors of caspase-1 (IC50 < 10 nM), with significant advantages over
      aldehydes such as high stability in vitro to thiols (10 mM dithiothreitol (pH
      7.2), 20 mM glutathione (pH 7.2, 9, 11)) and aqueous media, as well as some
      highly desirable druglike features. It was also demonstrated that azides can be
      incorporated into inhibitors of other caspases (e.g. 3, 8) and cathepsins (e.g.
      K, S, B), indicating the versatility of this valuable new approach to cysteine
      protease inhibition.

PMID- 16984173
TI  - Observation of heteronuclear overhauser effects confirms the 15N-1H dipolar
      relaxation mechanism in a crystalline protein.
AB  - The observation of proton to nitrogen-15 heteronuclear Overhauser effects in the
      microcrystalline protein Crh is used to confirm that the principal mechanism of
      relaxation of amide nitrogens is due to the fluctuation of the N-H dipolar
      couplings caused by N-H bond dynamics. Our observations reveal the central role
      of water as the main source of proton magnetization, and we provide an analysis
      of the different pathways that could lead to the observed results.

PMID- 16984174
TI  - Selective sp3 C-H activation of ketones at the beta position by Ir(I). Origin of
      regioselectivity and water effect.
AB  - The reaction of the cationic (PNP)Ir(I)(cyclooctene) complex (1) (PNP = 2,6-bis
      (di-tert-butylphosphinomethyl)pyridine) with 2-butanone or 3-pentanone results in
      the selective, quantitative activation of a beta C-H bond, yielding O,C-chelated
      complexes. Calculations show that the selectivity is both kinetically (because of
      steric reasons in the rate determingin step (RDS)) and thermodynamically
      controlled, the latter as a result of carbonyl oxygen coordination in the
      product. The RDS is formation of the eta2-C,H intermediates from the complexed
      ketone intermediates. Water has a strong influence on the regioselectivity, and
      in its presence, reaction of 1 with 2-butanone gives also the alpha terminal C-H
      activation product. Computational studies suggest that water can stabilize the
      terminal alpha C-H activation product by hydrogen bonding, forming a six-membered
      ring with the ketone, as experimentally observed in the X-ray structure of the
      acetonyl hydride aqua complex.

PMID- 16984175
TI  - Synthesis and electric field actuation of an ionic liquid polymer.
AB  - Polymerizable ionic liquids and their actuation in an electric field are a
      combination of material and properties with unique potential to display
      structural and fluid dynamics above that found in small molecule ionic liquids.
      In an effort to blend ionic liquid nature with actuation response, we have
      synthesized a new ionic liquid ammonium sulfonate monomer and polymer. The liquid
      temperature ranges of both the monomer and polymer ionic liquid systems are quite
      large extending from their respective glass transitions (Tg) of -57 and -49
      degrees C to decomposition at approximately 200 degrees C. Particularly
      remarkable is the small Tg increment that accompanies the transformation from
      monomer to polymer. The electrowetting behavior of the polymer and of the monomer
      presents an interesting contrast. This communication will encompass the
      polymerization, characterization, and actuation of these new ionic liquids.

PMID- 16984176
TI  - Photoisomerization of an individual azobenzene molecule in water: an on-off
      switch triggered by light at a fixed wavelength.
AB  - The alpha-hemolysin (alphaHL) pore was used as a nanoreactor for the direct
      observation of the reversible photoisomerization of individual tethered
      azobenzene molecules in an aqueous environment. alphaHL pores, PAZO, were used
      that had been derivatized within the lumen at a single cysteine residue with 4
      ((4-(2-chloroethanoamido)phenyl)diazenyl)benzenesulfonate. Trans-cis
      isomerizations were monitored at the single-molecule level by observing the
      modulation of the current passing through PAZO by electrical recording in planar
      bilayers. When PAZO was irradiated at 330 nm, continuous interconversion between
      the trans and cis states was observed. Either the trans or the cis state was
      maintained in the dark, depending upon which was present when the light source
      was shuttered. The cis state of PAZO was surprisingly stable in the dark, and no
      cis --> trans transitions were seen over a total observation period of more than
      8 h. Therefore, based on our findings, it might be possible to make fast digital
      nanoscale switches operated by light of a fixed wavelength.

PMID- 16984177
TI  - Synthesis of an aluminum spirocyclic hybrid with an inorganic B2O3 and an organic
      C3N2 core.
AB  - The reaction of LAl (L = HC(CMeNAr)2, Ar = 2,6-iPr2C6H3) or LAlH2 with PhB(OH)2
      yields the unprecedented spirocyclic LAl[(OBPh)2O] compound. The former reaction
      proceeds under hydrogen formation and simultaneous oxidation of the aluminum(I).

PMID- 16984178
TI  - Polymerization of ionized acetylene clusters into covalent bonded ions: evidence
      for the formation of benzene radical cation.
AB  - Since the discovery of acetylene and benzene in protoplanetary nebulae under
      powerful ultraviolet ionizing radiation, efforts have been made to investigate
      the polymerization of ionized acetylene. Here we report the efficient formation
      of benzene ions within gas-phase ionized acetylene clusters (C2H2)n+ with n = 3
      60. The results from experiments, which use mass-selected ion mobility
      techniques, indicate that the (C2H2)3+ ion has unusual stability similar to that
      of the benzene cation; its primary fragment ions are similar to those reported
      from the benzene cation, and it has a collision cross section of 47.4 A2 in
      helium at 300 K, similar to the value of 47.9 A2 reported for the benzene cation.
      In other words, (C2H2)3+ structurally looks like benzene, it has stability
      similar to that of benzene, it fragments such as benzene, therefore, it must be
      benzene!

PMID- 16984179
TI  - Design of a highly sensitive and specific nucleotide sensor based on photon
      upconverting particles.
AB  - We have designed and developed a novel sensor that reports the presence of
      specific nucleic acids in solutions, based on photon upconverting particles. The
      significantly high signal-to-noise ratio of photon upconverting particles leads
      to high sensitivity of the sensor. The sensor does not suffer from
      photobleaching. It also displays high specificity and self-calibrating
      capability. We expect nucleotide sensors of this type to be effective for
      applications in both DNA/RNA detection and protein-DNA/RNA interaction studies.

PMID- 16984180
TI  - Reversible three-state switching of luminescence: a new twist to electro- and
      photochromic behavior.
AB  - The fully reversible three-state blue/red/off emission from photo-/electrochromic
      substituted bis-thiaxanthylidenes is reported. The blue luminescence of the most
      stable (anti-folded) conformer of dimethyl- and dimethoxy-bis-thiaxanthylidene
      can be switched off by photochemical conversion to the meta-stable (syn-folded)
      conformer and switched on again by thermal reversion to the anti-folded state.
      The red luminescence of the bis-thiaxanthylium dication can be switched on by
      oxidation at approximately 1.0 and 1.2 V vs SCE of the syn- and anti-folded
      conformers respectively and switched off or to blue by reduction at approximately
      0.35 V vs SCE.

PMID- 16984181
TI  - Charge-transfer transitions in protein circular dichroism calculations.
AB  - Charge-transfer transitions in proteins play a key role in many biophysical
      processes, from the behavior of redox proteins to photochemical reactions. We
      present ab initio calculations on a model dipeptide and more approximate
      calculations of the electronic excited states of proteins which, taken together,
      provide the most definitive assignment and characterization of charge-transfer
      transitions in proteins to date. We have calculated from first principles the
      electronic circular dichroism (CD) spectra of 31 proteins on the basis of their
      structures. Compared to previous studies, we achieve more accurate calculated CD
      spectra between 170 and 190 nm, owing mainly to the importance in alpha-helices
      of a charge-transfer transition from the lone pair on one peptide group to the
      pi* orbital on the next peptide group.

PMID- 16984182
TI  - Isotope labeling studies reveal the order of oxygen incorporation into the
      tryptophan tryptophylquinone cofactor of methylamine dehydrogenase.
AB  - The bacterial enzyme methylamine dehydrogenase (MADH) contains the protein
      derived cofactor tryptophan tryptophylquinone (TTQ). TTQ is generated by the
      posttranslational modification of two endogenous MADH tryptophans, betaW57 and
      betaW108. Two oxygens are inserted sequentially into betaW57 to generate the
      quinone moiety, after which it is cross-linked to betaW108. We have previously
      shown that the second oxygenation and cross-link formation are catalyzed by the
      novel di-heme cytochrome MauG. Here we show, using isotopically labeled oxygen
      and water, that the first addition of oxygen occurs specifically at the C7
      position of betaW57 and that MauG then inserts the second oxygen at position C6.

PMID- 16984183
TI  - Increasing molecular weight parameters of a helical polymer through
      polymerization in a chiral solvent.
AB  - In this communication, we will demonstrate that polymerization in a chiral
      solvent can affect the molecular weight distribution of the product by perturbing
      the balance of the P and M helical screw senses of the growing chains.
      Specifically, for the Wurtz-type synthesis of polymethylphenylsilane (PMPS) in
      either (R) or (S)-limonene, the weight-average molecular weight of the products
      (average Mw = 80 000) was twice that of PMPS synthesized in (R/S)-limonene
      (average Mw = 39 200). Peturbation of the helical segmentation along the polymer
      chains leads to a reduction in the rate of occurrence of a key termination step.
      This the first time that a chiral solvent has been demonstrated to have such an
      effect on a polymerization process in affecting molecular weight parameters in
      contrast to affecting tacticity.

PMID- 16984184
TI  - A cost-effective method for the optical transduction of chemical reactions.
      Application to hyaluronidase inhibitor screening with polyarginine-counteranion
      complexes in lipid bilayers.
AB  - We report the systematic elaboration of a cost-effective, interference-minimized
      assay for the label-free optical transduction of chemical reactions. Recently, we
      have found that certain complexes formed by arginine-rich cell-penetrating
      peptides (CPPs) and amphiphilic counteranions can act as synergistic anion
      carriers in lipid bilayer membranes. Application of this discovery to rapid and
      reversible cytosolic CPP delivery has been described (Futaki, S.; et al. ACS
      Chem. Biol. 2006, 1, 299). Here, we report the complementary use of polyarginine
      (pR)-counteranion complexes as general optical transducers of chemical reactions.
      Counterion screening revealed dodecyl phosphate (DP) as an ideal pR activator.
      Carboxyfluorescein (CF)-loaded vesicles with a shelf life of 3.5 years served
      best for the detection of fluorogenic CF release by pR-DP complexes with the
      naked eye. Inactivation of pR-DP complexes by counterion exchange with hyaluronan
      (HA) caused no CF emission, while HA removal by hyaluronidase (HAase) did. pR-DP
      complexes were further compatible with the optical detection of HA immobilization
      on solid support as well as inhibitor screening for HAase (cromolyn, heparin)
      with and without substrate immobilization. Controls concerning binary ATP/ADP
      discrimination for naked-eye kinase detection are mentioned to delineate scope
      but also limitations of this simple and quite universal method.

PMID- 16984185
TI  - The discovery of an enantioselective receptor for (-)-adenosine from a racemic
      dynamic combinatorial library.
AB  - The use of laser polarimetry detection coupled with HPLC is demonstrated to
      enable the discovery of enantioselective receptors from racemic dynamic
      combinatorial libraries. Templating with an enantiopure analyte, such as (-)
      adenosine, leads to amplification of one enantiomer of the cyclic dimer. A result
      confirmed with a pseudo-racemic library wherein one of the enantiomers was d
      labeled for mass spec analysis. The resulting dimer is thus an enantioselective
      receptor for (-)-adenosine.

PMID- 16984186
TI  - A pro-chelator triggered by hydrogen peroxide inhibits iron-promoted hydroxyl
      radical formation.
AB  - The synthesis and structural characterization of a new pro-chelating agent,
      isonicotinic acid [2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene]
      hydrazide (BSIH), are presented. BSIH only weakly interacts with iron unless
      hydrogen peroxide (H2O2) is present to remove the boronic ester protecting group
      to reveal a phenol that is a key metal-binding group of tridentate
      salicylaldehyde isonicotinoyl hydrazone (SIH). BSIH prevents deoxyribose
      degradation caused by hydroxyl radicals that are generated from H2O2 and redox
      active iron by sequestering Fe3+ and preventing iron-promoted hydroxyl radical
      formation. The rate-determining step for iron sequestration is conversion of BSIH
      to SIH, followed by rapid Fe3+ complexation. The pro-chelate approach of BSIH
      represents a promising strategy for chelating a specific pool of detrimental
      metal ions without disturbing healthy metal ion distribution.

PMID- 16984187
TI  - Conjugated polymers in an arene sandwich.
AB  - A series of poly(p-arylene butadiynylene)s containing zero, one, and two co
      facial pi-pi interactions per repeat unit were synthesized and characterized. A
      surprisingly selective and high-yielding Diels-Alder cycloaddition of anthracene
      and nonsymmetric, sterically hindered anhydrides proved essential to generating
      the cofacial arene-containing monomers. Single-crystal X-ray structures display
      nearly parallel cofacial arenes that are within the van der Waals contact
      distances. The precursor molecules with cofacial arenes undergo reversible one-
      and two-electron oxidations to the radical cation and dication in CH2Cl2. The
      anhydrides were converted to N-alkyl imides to increase the solubility. High
      molecular weight poly(p-arylene butadiynylene)s were prepared via
      Pd/Cu(I)/benzoquinone oxidative coupling of the diacetylene monomers. The
      resulting polymers are highly emissive in solution and thin films. The ionization
      potentials were measured using ultraviolet photoelectron spectroscopy with thin
      films. Last, fluorescence measurements of polymer thin films during continuous
      irradiation indicate that the most hindered polymer is more resistant to
      photobleaching.

PMID- 16984188
TI  - Radial-position-controlled doping in CdS/ZnS core/shell nanocrystals.
AB  - In this paper, we report a new doping approach using a three-step synthesis to
      make high-quality Mn-doped CdS/ZnS core/shell nanocrystals. This approach allows
      precise control of the Mn radial position and doping level in the core/shell
      nanocrystals. On the basis of this synthetic advance, we have demonstrated the
      first example in which optical properties of Mn-doped nanocrystals strongly
      depend on Mn radial positions inside the nanocrystals. In addition, we have
      synthesized nanocrystals with a room-temperature Mn-emission quantum yield of
      56%, which is nearly twice as high as that of the best Mn-doped nanocrystals
      reported previously. Nanocrystals with such a high-emission quantum yield are
      very important to applications such as nanocrystal-based biomedical diagnosis.

PMID- 16984189
TI  - Stereoelectronic tuning of the structure and stability of the trp cage
      miniprotein.
AB  - Proline residues are critical structural elements in proteins, defining turns,
      loops, secondary structure boundaries, and polyproline helices. Control of
      proline conformation therefore may be used to define protein structure and
      stability. 4-Substituted proline derivatives may be used to control proline ring
      pucker, which correlates with protein main chain conformation. To examine the use
      of proline conformational restriction to tune globular protein stability, a
      series of peptides derived from the trp cage miniprotein was synthesized. Proline
      at residue 12 of the trp cage miniprotein, which adopts a Cgamma-exo ring pucker
      in the NMR structure, was replaced with 4-substituted proline derivatives,
      including 4R derivatives favoring a Cgamma-exo ring pucker and 4S derivatives
      favoring a Cgamma-endo ring pucker. Eight trp cage peptides were synthesized,
      five of which included residues that are not commercially available, without
      requiring any solution phase chemistry. Analysis of the trp cage peptides by
      circular dichroism and NMR indicated that the structure and stability of the trp
      cage miniprotein was controllable based on the conformational bias of the proline
      derivative. Replacement of Pro12 with 4S-substituted proline derivatives that
      favor the Cgamma-endo ring pucker destabilized the trp cage, while replacement of
      Pro12 with 4R-substituted proline derivatives that favor a Cgamma-exo ring pucker
      resulted in increased alpha-helicity and thermal stability of the trp cage. The
      most stable trp cage derivatives contained benzoates of 4R-hydroxyproline, which
      also exhibited the most pronounced stereoelectronic effects in TYProxN model
      peptides. Overall, the stability of the trp cage was tunable by over 50 degrees C
      depending on the identity of the proline side chain at residue 12.

PMID- 16984190
TI  - Strong cooperative enhancement of two-photon absorption in double-strand
      conjugated porphyrin ladder arrays.
AB  - We present the two-photon absorption (2PA) spectra of a series of conjugated
      porphyrin oligomers containing N = 2, 4, 8, and ca. 13 monomer units, meso-meso
      connected with butadiyne linkers. We demonstrate that, in the coplanar double
      strand arrays, self-assembled upon addition of 4,4'-bipyridyl, the conjugation
      length increases dramatically, leading to very strong cooperative enhancement of
      2PA. We analyze the scaling of 2PA in both the double-strand and rotationally
      free single-strand arrays and show how the effective conjugation length in both
      cases is linked to the observed 2PA properties. By introducing a "conjugation
      signature" for the 2PA strength, we show that, in double-strand arrangement, the
      conjugation embraces the whole molecule up to the tetramer level, whereas in
      single-strand arrangement, it is always less than N, except for N = 2, but keeps
      increasing until N = 8. Our finding of extremely strong 2PA cross section, sigma2
      approximately 105 GM, in double-strand oligomers peaking at 1.3 mum can find use
      for signal processing in fiber-optic devices.

PMID- 16984191
TI  - Direct observation of reductive elimination of methyl iodide from a rhodium(III)
      pincer complex: the importance of sterics.
AB  - A rare case of directly observed alkyl halide reductive elimination from rhodium
      is reported. Treatment of the naphthyl-based PCP-type Rh(III) methyl complexes
      2a,b [(C10H5(CH2PR2)2)Rh(CH3)(I)] (R = iPr 2a, R = tBu 2b) with CO resulted in
      facile reductive elimination of methyl iodide in the case of 2b, yielding the
      Rh(I) carbonyl complex [(C10H5(CH2PR2)2)Rh(CO)] 3b (R = tBu), while the less
      bulky 2a formed CO adducts and did not undergo reductive elimination, contrary to
      expectations based on electron density considerations. Moreover, 3b oxidatively
      added methyl iodide, while 3a did not. CD3I/CH3I exchange studies in the absence
      of CO indicate that reversible formation of (ligated) methyl iodide takes place
      in both systems. Subsequently, when CO is present, it displaces methyl iodide in
      the bulkier tBu system, whereas with the iPr system formation of the Rh(III) CO
      adducts is favored. Iodide dissociation followed by its attack on the rhodium
      methyl group is unlikely.

PMID- 16984192
TI  - Molecular-wire behavior of OLED materials: exciton dynamics in multichromophoric
      Alq3-oligofluorene-Pt(II)porphyrin triads.
AB  - Donor-bridge-acceptor triads consisting of the Alq3 complex, oligofluorene
      bridge, and PtII tetraphenylporphyrin (PtTPP) were synthesized. The triads were
      designed to study the energy level/distance-dependence in energy transfer both in
      a solution and in solid state. The materials show effective singlet transfer from
      the Alq3-fluorene fluorophore to the porphyrin, while the triplet energy
      transfer, owing to the shorter delocalization of triplet excitons, appears to
      take place via a triplet energy cascade. Using femtosecond transient
      spectroscopy, the rate of the singlet-singlet energy transfer was determined. The
      exponential dependence of the donor-acceptor distance and the respective energy
      transfer rates of 7.1 x 1010 to 1.0 x 109 s-1 with the attenuation factor a of
      0.21 +/- 0.02 A-1 suggest that the energy transfer proceeds via a mixed
      incohererent wire/superexchange mechanism. In the OLEDs fabricated using the Alq3
      oligofluorene-PtTPP triads with better triplet level alignment, the order of a
      magnitude increase in efficacy appears to be due to facile triplet energy
      transfer. The devices, where the triplet-triplet energy transfer is of paramount
      importance, showed high color purity emission (CIE X,Y: 0.706, 0.277), which is
      almost identical to the emission from thin films. Most importantly, we believe
      that the design principles demonstrated above are general and may be used to
      prepare OLED materials with enhanced quantum efficacy at lowered operational
      potentials, being crucial for improved lifespan of OLEDs.

PMID- 16984193
TI  - Hydration and dewetting near fluorinated superhydrophobic plates.
AB  - The water dynamics near nanoscale fluorinated (CF(3)(CF(2))(7)(CH(2))(2)SiH(3))
      monolayers (plates) as well as possible dewetting transitions in-between two such
      plates have been studied with molecular dynamics simulations in this paper. A
      "weak water depletion" is found near the single fluorinated surface, with an
      average water density in the first solvation shells 6-8% lower than its
      hydrogenated counterpart. The fluorinated molecules are also found to be water
      impermeable, consistent with experimental findings. More surprisingly, a
      dewetting transition is found in the interplate region with a critical distance
      D(c) of 10 A (3-4 water diameters) for double plates with 8 x 8 molecules each
      (plate size approximately 4 nm x 4 nm). This transition, although occurring on a
      microscopic length scale, is reminiscent of a first-order phase transition from
      liquid to vapor. The unusual superhydrophobicity of fluorocarbons is found to be
      related to their larger size (or surface area) as compared to hydrocarbons, which
      "dilutes" their physical interactions with water. The water-plate interaction
      profile shows that the fluorinated carbons have a 10-12% weaker water-plate
      interaction than their hydrogenated counterparts in the nearest solvation shell,
      even though the fluorocarbons do have a stronger electrostatic interaction with
      water due to their larger partial charges. However, the van der Waals
      interactions dominate the water-plate interaction within the nearest shell, with
      up to 90% contributions to the total interaction energy, and fluorocarbons have a
      noticeably weaker (by 10-15%) van der Waals interaction with water in the nearest
      shell than do hydrocarbons. Both the slightly weaker water-plate interaction and
      larger surface area contribute to the stronger dewetting transition in the
      current fluorinated carbon plates.

PMID- 16984194
TI  - Methane dehydrogenation on Rh@Cu(111): a first-principles study of a model
      catalyst.
AB  - The issue of tuning the relative height of the first two dehydrogenation barriers
      of methane (CH(4) --> CH(3) + H and CH(3) --> CH(2) + H) is addressed using
      density-functional theory. It is shown that the combination of a very active
      reaction center-such as Rh-with a more inert substrate-such as Cu(111)-may hinder
      the second dehydrogenation step with respect to the first, thus resulting in the
      reverse of the natural order of the two barriers' heights.

PMID- 16984195
TI  - Heme protein oxygen affinity regulation exerted by proximal effects.
AB  - Heme proteins are found in all living organisms and are capable of performing a
      wide variety of tasks, requiring in many cases the binding of diatomic ligands,
      namely, O(2), CO, and/or NO. Therefore, subtle regulation of these diatomic
      ligands' affinity is one of the key issues for determining a heme protein's
      function. This regulation is achieved through direct H-bond interactions between
      the bound ligand and the protein, and by subtle tuning of the intrinsic heme
      group reactivity. In this work, we present an investigation of the proximal
      regulation of oxygen affinity in Fe(II) histidine coordinated heme proteins by
      means of computer simulation. Density functional theory calculations on heme
      model systems are used to analyze three proximal effects: charge donation,
      rotational position, and distance to the heme porphyrin plane of the proximal
      histidine. In addition, hybrid quantum-classical (QM-MM) calculations were
      performed in two representative proteins: myoglobin and leghemoglobin. Our
      results show that all three effects are capable of tuning the Fe-O(2) bond
      strength in a cooperative way, consistently with the experimental data on oxygen
      affinity. The proximal effects described herein could operate in a large variety
      of O(2)-binding heme proteins-in combination with distal effects-and are
      essential to understand the factors determining a heme protein's O(2) affinity.

PMID- 16984196
TI  - Lipids out of equilibrium: energetics of desorption and pore mediated flip-flop.
AB  - The potential of mean force (PMF) of a phospholipid in a bilayer is a key
      thermodynamic property that describes the energetic cost of localized lipid
      defects. We have calculated the PMF by umbrella sampling using molecular dynamics
      simulations. The profile has a deep minimum at the equilibrium position in the
      bilayer and steeply rises for displacements both deeper into the bilayer and
      moving away from the bilayer. As the lipid loses contact with the bilayer, the
      profile abruptly flattens without a significant barrier. The calculated free
      energy difference of 80 kJ/mol between the minimum of the PMF and the value in
      water agrees well with the free energy difference calculated from the
      experimentally measured critical micelle concentration. Significant water/lipid
      defects form when a lipid is forced into the bilayer interior, in the form of a
      small water pore that spans the membrane. The energy required to form such a
      water pore is also found to be 80 kJ/mol. On the basis of this energy, we
      estimate the lipid flip-flop rate and permeability rate of sodium ions. The
      resulting rates are in good agreement with experimental measurements, suggesting
      lipid flip-flop and basal permeability of ions are pore mediated.

PMID- 16984197
TI  - Elasticity of crystalline beta-sheet monolayers.
AB  - Designed amphiphilic beta-sheet peptides with the sequence Pro-Glu-(Phe-Glu)(n)
      Pro (n = 2-7) were previously shown by grazing incidence X-ray diffraction
      (GIXD), to form ordered two-dimensional (2-D) monolayer structures at interfaces
      induced by the proline residues at peptide termini. The GIXD diffraction pattern
      was modeled with two coexisting lattice arrangements, suggesting structural
      flexibility exhibited in the multiple ways by which beta-strands and their amino
      acid side chains pack into ordered 2-D structures. Here, we find by in-situ GIXD
      measurements that the ordered beta-sheet assemblies may undergo a quasi
      reversible compression and expansion cycle at the air-water interface. The
      diffraction measurements indicate that on compression the repeat distance that
      corresponds to the long axes of the peptide strands may decrease by up to 37% in
      length. Upon expansion the compressed beta-sheet assemblies revert elastically to
      their original conformation. The interstrand repeat distance along the peptide
      hydrogen bonds apparently does not change along the film compression and
      expansion. Based on the GIXD data, at surface pressures higher than approximately
      3 mN/m, beyond the peptide limiting area per molecule, the compressibility is 7.4
      +/- 0.6 m/N. The out-of-plane Bragg rod diffraction patterns imply that in the
      compressed state the beta-strands buckle up in reaction to the increase in
      surface pressure. At low surface pressure, the 2-D compressibility of the
      crystalline beta-sheet was estimated at approximately 32 m/N attributed to
      interdomain rearrangements.

PMID- 16984198
TI  - Arsenic binding to human metallothionein.
AB  - The number of reported cases of chronic arsenic poisoning is on the rise
      throughout the world, making the study of the long-term effects of arsenic
      critical. As(3+) binds readily to biological thiols, including mammalian
      metallothionein (MT), which is an ubiquitous sulfur-rich metalloprotein known to
      coordinate a wide range of metals. The two-domain mammalian protein binds
      divalent metals (M) into two metal-thiolate clusters with stoichiometries of
      M(3)S(cys9) (beta) and M(4)S(cys11) (alpha). We report that As(3+) binds with
      stoichiometries of As(3)S(cys9) (beta) and As(3)S(cys11) (alpha) to the
      recombinant human metallothionein (rhMT) isoform 1a protein. Further, we report
      the complete kinetic analysis of the saturation reactions of the separate alpha
      and beta domains of rhMT with As(3+). Speciation in the metalation reactions was
      determined using time- and temperature-resolved electrospray ionization mass
      spectrometry. The binding reaction of As(3+) to the alpha and beta MT domains is
      shown to be noncooperative and involves three sequential, bimolecular metalation
      steps. The analyses allow for the first time the complete simulation of the
      experimental data for the stepwise metalation reaction of MT showing the relative
      concentrations of the metal-free, apo MT and each of the As-MT intermediate
      species as a function of time and temperature. At room temperature (298 K) and pH
      3.5, the individual rate constants for the first, second, and third As(3+)
      binding to apo-alphaMT are 5.5, 6.3, and 3.9 M(-)(1) s(-)(1) and for apo-betaMT
      the constants are 3.6, 2.0, and 0.6 M(-)(1) s(-)(1). The activation energy for
      formation of As(1)-H(6)-betaMT is 32 kJ mol(-)(1), for As(2)-H(3)-betaMT it is 35
      kJ mol(-)(1), for As(3)-betaMT it is 29 kJ mol(-)(1), for As(1)-H(8)-alphaMT it
      is 33 kJ mol(-)(1), for As(2)-H(5)-alphaMT it is 29 kJ mol(-)(1), and for As(3)
      H(2)-alphaMT it is 23 kJ mol(-)(1).

PMID- 16984199
TI  - A 2H NMR relaxation experiment for the measurement of the time scale of methyl
      side-chain dynamics in large proteins.
AB  - An NMR experiment is presented for the measurement of the time scale of methyl
      side-chain dynamics in proteins that are labeled with methyl groups of the
      (13)CHD(2) variety. The measurement is accomplished by selecting a magnetization
      mode that to excellent approximation relaxes in a single-exponential manner with
      a T(1)-like rate. The combination of R(1)((13)CHD(2)) and R(2)((13)CHD(2)) (2)H
      relaxation rates facilitates the extraction of motional parameters from
      (13)CHD(2)-labeled proteins exclusively. The utility of the methodology is
      demonstrated with applications to proteins with tumbling times ranging from 2 ns
      (protein L, 7.5 kDa, 45 degrees C) to 54 ns (malate synthase G, 82 kDa, 37
      degrees C); dynamics parameters are shown to be in excellent agreement with those
      obtained in (2)H NMR studies of other methyl isotopomers. A consistency
      relationship is found to exist between R(1)((13)CHD(2)) and the relaxation rates
      of pure longitudinal and quadrupolar order modes in (13)CH(2)D-labeled methyl
      groups, and experimental rates measured for a number of proteins are shown to be
      in excellent agreement with expectations based on theory. The present methodology
      extends the applicability of (2)H relaxation methods for the quantification of
      side-chain dynamics in high molecular weight proteins.

PMID- 16984200
TI  - Synthesis and structural characterization of 1-mesityl-1,3-dihydro-imidazole-2
      selone and bis(1-mesitylimidazol-2-yl)diselenide: experimental evidence that the
      selone is more stable than the selenol tautomer.
AB  - 1-Mesityl-1,3-dihydro-imidazole-2-selone, (seim(Mes))H, may be obtained from 1
      mesitylimidazole via (i) deprotonation with Bu(n)Li, (ii) treatment with
      elemental selenium, and (iii) addition of HCl(aq). Structural characterization of
      (seim(Mes))H by X-ray diffraction demonstrates that the compound exists as the
      selone rather than selenol tautomer, a result that is in accord with DFT
      calculations. Solutions of (seim(Mes))H are oxidized by air to give bis(1
      mesitylimidazol-2-yl)diselenide, (seim(Mes))(2). A corresponding investigation of
      (seim(Me))H demonstrates that, in contrast to a previous report, the selenium
      analogue of methimazole exists in the selone form with a structure analogous to
      that of methimazole. (1)H and (77)Se NMR studies demonstrate that the (seim(R))
      groups of the selone (seim(R))H and diselenide (seim(R))(2) undergo facile
      exchange on the NMR time scale.

PMID- 16984201
TI  - Quasi-isomeric gallium amides and imides GaNR2 and RGaNR (R = organic group):
      reactions of the digallene, Ar'GaGaAr' (Ar' = C6H3-2,6-(C6H3-2,6-Pri2)2) with
      unsaturated nitrogen compounds.
AB  - Reactions of the "digallene" Ar'GaGaAr'(1) (Ar' = C(6)H(3)-2,6-(C(6)H(3)-2,6
      Pr(i)(2))(2)), which dissociates to green :GaAr' monomers in solution, with
      unsaturated N-N-bonded molecules are described. Treatment of solutions of :GaAr'
      with the bulky azide N(3)Ar(#) (Ar(#) = C(6)H(3)-2,6-(C(6)H(2)-2,6-Me(2)-4
      Bu(t))(2)), afforded the red imide Ar'GaNAr(#) (2). Addition of the azobenzenes,
      ArylNNAryl (Aryl = C(6)H(4)-4-Me (p-tolyl), mesityl, and C(6)H(3)-2,6-Et(2))
      yielded the 1,2-Ga(2)N(2) ring compound Ar'GaN(p-tolyl)N(p-tolyl)GaA' (3) or the
      products MesN=NC(6)H(2)-2,4-Me(2)-6-Ga(Me)Ar' (4) and 2,6
      Et(2)C(6)H(3)N=NC(6)H(3)-2-Et-6-Ga(Et)Ar' (5). Reaction of GaAr' with N(2)CPh(2)
      yielded the 1,3-Ga(2)N(2) ring compound Ar'Ga(mu:eta(1)-N(2)CPh(2))(2)GaAr' (6),
      which is quasi-isomeric to 3. Calculations on simple model isomers showed that
      the Ga(I) amide GaNR(2) (R = Me) is much more stable than the isomeric Ga(III)
      imide RGaNR. This led to the synthesis of the first stable monomeric Ga(I) amide,
      GaN(SiMe(3))Ar' ' (8) (Ar' ' = C(6)H(3)-2,6-(C(6)H(2)-2,4,6-Me(3))(2) from the
      reaction of LiN(SiMe(3))Ar' ' (7) and "GaI". Compound 8 is also the first one
      coordinate gallium species to be characterized in the solid state. The reaction
      of 8 with N(3)Ar' ' afforded the amido-imide derivative Ar' 'NGaN(SiMe(3))Ar' '
      (9), a gallium nitrogen analogue of an allyl anion. All compounds were
      spectroscopically and structurally characterized. In addition, DFT calculations
      were performed on model compounds of the amide, imide, and cyclic 1,2- and 1,3
      species to better understand their bonding. The pairs of compounds 2 and 8 as
      well as 3 and 6 are rare examples of quasi-isomeric heavier main group element
      compounds.

PMID- 16984203
TI  - The arginine anomaly: arginine radicals are poor hydrogen atom donors in electron
      transfer induced dissociations.
AB  - Arginine amide radicals are generated by femtosecond electron transfer to
      protonated arginine amide cations in the gas phase. A fraction of the arginine
      radicals formed (2-amino-5-dihydroguanid-1'-yl-pentanamide, 1H) is stable on the
      6.7 micros time scale and is detected after collisional reionization. The main
      dissociation of 1H is loss of a guanidine molecule from the side chain followed
      by consecutive dissociations of the 2-aminopentanamid-5-yl radical intermediate.
      Intramolecular hydrogen atom transfer from the guanidinium group onto the amide
      group is not observed. These results are explained by ab initio and density
      functional theory calculations of dissociation and transition state energies.
      Loss of guanidine from 1H is calculated to require a transition state energy of
      68 kJ mol(-)(1), which is substantially lower than that for hydrogen atom
      migration from the guanidine group. The loss of guanidine competes with the
      reverse migration of the arginine alpha-hydrogen atom onto the guanidyl radical.
      RRKM calculations of dissociation kinetics predict the loss of guanidine to
      account for >95% of 1H dissociations. The anomalous behavior of protonated
      arginine amide upon electron transfer provides an insight into electron capture
      and transfer dissociations of peptide cations containing arginine residues as
      charge carriers. The absence of efficient hydrogen atom transfer from charge
      reduced arginine onto sterically proximate amide group blocks one of the current
      mechanisms for electron capture dissociation. Conversely, charge-reduced
      guanidine groups in arginine residues may function as radical traps and induce
      side-chain dissociations. In light of the current findings, backbone
      dissociations in arginine-containing peptides are predicted to involve excited
      electronic states and proceed by the amide superbase mechanism that involves
      electron capture in an amide pi* orbital, which is stabilized by through-space
      coulomb interaction with the remote charge carriers.

PMID- 16984204
TI  - Synthesis, reactivity, and DFT studies of tantalum complexes incorporating
      diamido-N-heterocyclic carbene ligands. Facile endocyclic C-H bond activation.
AB  - The syntheses of tantalum derivatives with the potentially tridentate diamido-N
      heterocyclic carbene (NHC) ligand are described. Aminolysis and alkane
      elimination reactions with the diamine-NHC ligands, (Ar)[NCN]H(2) (where
      (Ar)[NCN]H(2) = (ArNHCH(2)CH(2))(2)(C(3)N(2)); Ar = Mes, p-Tol), provided
      complexes with a bidentate amide-amine donor configuration. Attempts to promote
      coordination of the remaining pendent amine donor were unsuccessful. Metathesis
      reactions with the dilithiated diamido-NHC ligand ((Ar)[NCN]Li(2)) and various
      Cl(x)Ta(NR'(2))(5-)(x) precursors were successful and generated the desired
      octahedral (Ar)[NCN]TaCl(x)(NR'(2))(3-)(x) complexes. Attempts to prepare
      trialkyl tantalum complexes by this methodology resulted in the formation of an
      unusual metallaaziridine derivative. DFT calculations on model complexes show
      that the strained metallaaziridine ring forms because it allows the remaining
      substituents to adopt preferable bonding positions. The calculations predict that
      the lowest energy pathway involves a tantalum alkylidene intermediate, which
      undergoes C-H bond activation alpha to the amido to form the metallaaziridine
      moiety. This mechanism was confirmed by examining the distribution of deuterium
      atoms in an experiment between (Mes)[NCN]Li(2) and Cl(2)Ta(CD(2)Ph)(3). The
      single-crystal X-ray structures of (p)(-Tol)[NCNH]Ta(NMe(2))(4) (3),
      (Mes)[NCNH]Ta=CHPh(CH(2)Ph)(2) (4), (p)(-Tol)[NCN]Ta(NMe(2))(3) (7),
      (Mes)[NCCN]Ta(CH(2)(t)Bu)(2) (11), and (Mes)[NCCN]TaCl(CH(2)(t)Bu) (14) are
      included.

PMID- 16984205
TI  - Dendrimer-functionalized single-wall carbon nanotubes: synthesis,
      characterization, and photoinduced electron transfer.
AB  - We describe the synthesis and characterization of a series of single-wall carbon
      nanotubes (SWNTs) functionalized with polyamidoamine dendrimers. Importantly, the
      dendrimers are linked directly to the SWNT surface using a divergent methodology.
      This approach allows the number of functional groups on the nanotubes to be
      increased without provoking significant damage to the conjugated pi-system of the
      SWNTs. Several tetraphenylporphyrin moieties can be linked to the periphery of
      the dendrimers, and the photophysical properties of the resulting nanoconjugates
      have been investigated with a series of steady-state and time-resolved
      spectroscopy. The fluorescence kinetics provide evidence for two transient
      decays, one very short-lived (i.e., 0.04 +/- 0.01 ns) and one long-lived (i.e.,
      8.6 +/- 1.2 ns). A possible explanation is that some porphyrin units do not
      interact with the nanotubes, thus exhibiting a fluorescence lifetime similar to
      that of the free porphyrin. Complementary transient absorption measurements not
      only corroborate the fast decay of the photoexcited tetraphenylporphyrin but also
      confirm that intraconjugate charge separation evolves from the excited porphyrin
      to the SWNTs.

PMID- 16984202
TI  - Specificity of human thymine DNA glycosylase depends on N-glycosidic bond
      stability.
AB  - Initiating the DNA base excision repair pathway, DNA glycosylases find and
      hydrolytically excise damaged bases from DNA. While some DNA glycosylases exhibit
      narrow specificity, others remove multiple forms of damage. Human thymine DNA
      glycosylase (hTDG) cleaves thymine from mutagenic G.T mispairs, recognizes many
      additional lesions, and has a strong preference for nucleobases paired with
      guanine rather than adenine. Yet, hTDG avoids cytosine, despite the million-fold
      excess of normal G.C pairs over G.T mispairs. The mechanism of this remarkable
      and essential specificity has remained obscure. Here, we examine the possibility
      that hTDG specificity depends on the stability of the scissile base-sugar bond by
      determining the maximal activity (k(max)) against a series of nucleobases with
      varying leaving-group ability. We find that hTDG removes 5-fluorouracil 78-fold
      faster than uracil, and 5-chlorouracil, 572-fold faster than thymine, differences
      that can be attributed predominantly to leaving-group ability. Moreover, hTDG
      readily excises cytosine analogues with improved leaving ability, including 5
      fluorocytosine, 5-bromocytosine, and 5-hydroxycytosine, indicating that cytosine
      has access to the active site. A plot of log(k(max)) versus leaving-group pK(a)
      reveals a Bronsted-type linear free energy relationship with a large negative
      slope of beta(lg) = -1.6 +/- 0.2, consistent with a highly dissociative reaction
      mechanism. Further, we find that the hydrophobic active site of hTDG contributes
      to its specificity by enhancing the inherent differences in substrate reactivity.
      Thus, hTDG specificity depends on N-glycosidic bond stability, and the
      discrimination against cytosine is due largely to its very poor leaving ability
      rather than its exclusion from the active site.

PMID- 16984206
TI  - Pi-complex structure of gaseous benzene-NO cations assayed by IR multiple photon
      dissociation spectroscopy.
AB  - [C(6)H(6)NO](+) ions, in two isomeric forms involved as key intermediates in the
      aromatic nitrosation reaction, have been produced in the gas phase and analyzed
      by IR multiple photon dissociation (IRMPD) spectroscopy in the 800-2200 cm(-)(1)
      fingerprint wavenumber range, exploiting the high fluence and wide tunability of
      a free electron laser (FEL) source. The IRMPD spectra were compared with the IR
      absorption spectra calculated for the optimized structures of potential isomers,
      thus allowing structural information on the absorbing species. [C(6)H(6)NO](+)
      ions were obtained by two routes, taking advantage of the FEL coupling to two
      different ion traps. In the first one, an FT-ICR mass spectrometer, a sequence of
      ion-molecule reactions was allowed to occur, ultimately leading to an NO(+)
      transfer process to benzene. The so-formed ions displayed IRMPD features
      characteristic of a [benzene,NO](+) pi-complex structure, including a prominent
      band at 1963 cm(-)(1), within the range for the N-O bond stretching vibration of
      NO (1876 cm(-)(1)) and NO(+) (2344 cm(-)(1)). A quite distinct species is formed
      by electrospray ionization (ESI) of a methanol solution of nitrosobenzene. The
      ions transferred and stored in a Paul ion trap showed the IRMPD features of
      substituent protonated nitrosobenzene, the most stable among conceivable
      [C(6)H(6)NO](+) isomers according to computations. It is noteworthy that IRMPD is
      successful in allowing a discrimination between isomeric [C(6)H(6)NO](+) species,
      whereas high-energy collision-induced dissociation fails in this task. The
      [benzene,NO](+) pi-complex is characterized by IRMPD spectroscopy as an exemplary
      noncovalent ionic adduct between two important biomolecular moieties.

PMID- 16984207
TI  - Studies on the mechanism of action of prekinamycin, a member of the
      diazoparaquinone family of natural products: evidence for both sp2 radical and
      orthoquinonemethide intermediates.
AB  - The putative reductive activation chemistry of the diazoparaquinone antibiotics
      was modeled with Bu(3)Sn-H and prekinamycin dimethyl ether along with
      prekinamycin itself. Reaction in various combinations of aromatic solvents, with
      and without the nucleophile benzylmercaptan present, led to isolation of both
      radical-trapping arene adducts and nucleophilic capture benzyl thioether
      products. On the basis of these product distribution studies, the intermediacies
      of, first, a cyclopentenyl radical and, next, an orthoquinonemethide electrophile
      are postulated.

PMID- 16984208
TI  - Sequence-specific recognition and cooperative dimerization of N-terminal aromatic
      peptides in aqueous solution by a synthetic host.
AB  - This article describes the selective recognition and noncovalent dimerization of
      N-terminal aromatic peptides in aqueous solution by the synthetic host compound,
      cucurbit[8]uril (Q8). Q8 is known to bind two aromatic guests simultaneously and,
      in the presence of methyl viologen, to recognize N-terminal tryptophan over
      internal and C-terminal sequence isomers. Here, the binding of Q8 to aromatic
      peptides in the absence of methyl viologen was studied by isothermal titration
      calorimetry (ITC), (1)H NMR spectroscopy, and X-ray crystallography. The peptides
      studied were of sequence X-Gly-Gly, Gly-X-Gly, and Gly-Gly-X (X = Trp, Phe, Tyr,
      and His). Q8 selectively binds and dimerizes Trp-Gly-Gly (1) and Phe-Gly-Gly (4)
      with high affinity (ternary K = 10(9)-10(11) M(-)(2)); binding constants for the
      other 10 peptides were too small to be measured by ITC. Both peptides bound in a
      stepwise manner, and peptide 4 bound with positive cooperativity. Crystal
      structures of Q8.1 and Q8.4(2) reveal the basis for selective recognition as
      simultaneous inclusion of the hydrophobic aromatic side chain into the cavity of
      Q8 and chelation of the proximal N-terminal ammonium group by carbonyl groups of
      Q8. The peptide sequence selectivity and positively cooperative dimerization
      reported here are, to the best of our knowledge, unprecedented for synthetic
      hosts in aqueous solution. Specific peptide recognition and dimerization by
      synthetic hosts such as Q8 should be important in the study of dimer-mediated
      biochemical processes and for the separation of peptides and proteins.

PMID- 16984209
TI  - One-electron reduction of kinetically stabilized dipnictenes: synthesis of
      dipnictene anion radicals.
AB  - The redox behavior of kinetically stabilized dipnictenes, BbtE=EBbt [E = P, Sb,
      Bi; Bbt = 2,6-bis[bis(trimethylsilyl)methyl]-4
      [tris(trimethylsilyl)methyl]phenyl], was systematically disclosed using cyclic
      voltammetry and theoretical calculations. It was found that they showed
      reversible one-electron redox couples in the reduction region. The anion radical
      species of the Bbt-substituted diphosphene and distibene were successfully
      synthesized by the reduction of the corresponding neutral dipnictenes (BbtP=PBbt
      and BbtSb=SbBbt). Their structures were reasonably characterized by ESR, UV-vis,
      and Raman spectroscopy, and the distibene anion radical was structurally
      characterized by X-ray crystallographic analysis.

PMID- 16984210
TI  - Ethnic or racial differences revisited: impact of dosage regimen and dosage form
      on pharmacokinetics and pharmacodynamics.
AB  - Ethnic or racial differences in pharmacokinetics and pharmacodynamics have been
      attributed to the distinctions in the genetic, physiological and pathological
      factors between ethnic/racial groups. These pharmacokinetic/pharmacodynamic
      differences are also known to be influenced by several extrinsic factors such as
      socioeconomic background, culture, diet and environment. However, it is noted
      that other factors related to dosage regimen and dosage form have largely been
      ignored or overlooked when conducting or analysing
      pharmacokinetic/pharmacodynamic studies in relation to ethnicity/race. Potential
      interactions can arise between the characteristics of ethnicity/race and a unique
      feature of dosage regimen or dosage form used in the study, which may partly
      account for the observed pharmacokinetic/pharmacodynamic differences between
      ethnic/racial groups. Ethnic/racial differences in
      pharmacokinetics/pharmacodynamics can occur from drug administration through a
      specific route that imparts distinct pattern of absorption, distribution,
      transport, metabolism or excretion. For example, racial differences in the first
      pass metabolism of a drug following oral administration may not be relevant when
      the drug is applied to the skin. On the other hand, ethnic/racial difference in
      pharmacokinetics/pharmacodynamics can also happen via two different routes of
      drug delivery, with varying levels of dissimilarity between routes. For example,
      greater ethnic/racial differences were observed in oral clearance than in
      systemic clearance of some drugs, which might be explained by the pre-systemic
      factors involved in the oral administration as opposed to the intravenous
      administration. Similarly, changes in the dose frequency and/or duration may have
      profound impact on the ethnic/racial differences in
      pharmacokinetic/pharmacodynamic outcome. Saturation of enzymes, transporters or
      receptors at high drug concentrations is a possible reason for many observed
      ethnic/racial discrepancies between single- and multiple-dose regimens, or
      between low- and high-dose administrations. The presence of genetic polymorphism
      of enzymes and/or transporters can further complicate the analysis of
      pharmacokinetic/pharmacodynamic data in ethnic/racial populations. Even within
      the same dosage regimen, the use of different dosage forms may trigger
      significantly different pharmacokinetic/pharmacodynamic responses in various
      ethnic/racial groups, given that different dosage forms may exhibit different
      rates of drug release, may release the drug at different sites, and/or have
      different retention times at specific sites of the body. It is thus cautioned
      that the pharmacokinetic/pharmacodynamic data obtained from different
      ethnic/racial groups cannot be indiscriminately compared or combined for analysis
      if there is a lack of homogeneity in the apparent 'extrinsic' factors, including
      dosage regimen and dosage form.

PMID- 16984212
TI  - Absolute oral bioavailability of traxoprodil in cytochrome P450 2D6 extensive and
      poor metabolisers.
AB  - BACKGROUND: Traxoprodil, a substituted 4-phenylpiperidine, is an N-methyl-D
      aspartate (NMDA) receptor antagonist that is selective for receptors containing
      the NR2B subunit. In vivo and in vitro studies examining the disposition of
      traxoprodil have demonstrated that it is mainly metabolised by cytochrome P450
      (CYP) 2D6, a major drug-metabolising enzyme that exhibits a genetic polymorphism.
      OBJECTIVE: To assess the single-dose absolute oral bioavailability of traxoprodil
      in healthy male volunteers phenotyped as either CYP2D6 extensive or poor
      metabolisers. METHODS: This was an open-label, three-way crossover study.
      Traxoprodil was administered as a single dose orally in solution of 50, 100 and
      300mg and intravenously as a constant rate 2-hour infusion of 50 and 100mg.
      CYP2D6 phenotype was assigned following single-dose dextromethorphan
      administration. RESULTS: In poor metabolisers (n = 6), oral bioavailability was
      approximately 80% and was consistent with a liver extraction ratio of
      approximately 20% (plasma clearance of approximately 4 mL/min/kg) indicating near
      complete absorption. Following intravenous administration, the mean volume of
      distribution at steady state (V(ss)) was moderate (approximately 6.5 L/kg) and
      the mean elimination half-life (t((1/2))) was approximately 20 hours. Following
      oral administration the mean maximum plasma concentration (C(max)) and area under
      the plasma concentration-time curve from time zero to infinity (AUC(infinity))
      increased approximately proportionally with dose. In extensive metabolisers (n =
      11), oral bioavailability was dose-dependent and nonlinear. At the 100mg dose,
      the absolute oral bioavailability was approximately 39.5%. Overall, the oral
      bioavailability ranged from 22.8% to 62.1% and its estimation was confounded by
      large differences in plasma concentrations at oral doses without equivalent
      intravenous doses. Following intravenous administration, plasma clearance was
      high (approximately 27 mL/min/kg), the V(ss) was moderate (approximately 4 L/Kg)
      and the t((1/2)) was approximately 2-4 hours. Following oral administration the
      C(max) and AUC(infinity) increased more than proportionally with dose. Apparent
      oral clearance decreased with increasing oral dose. However, t((1/2)) was
      approximately the same at all doses (approximately 4 hours). CONCLUSION: The
      pharmacokinetics of traxoprodil were quite different in the two phenotypes. In
      extensive metabolisers, the oral bioavailability was nonlinear and dose
      dependent, while in poor metabolisers, oral bioavailability appeared to be linear
      and dose-independent. Based on the pharmacokinetics in extensive and poor
      metabolisers, the nonlinear oral bioavailability in extensive metabolisers may be
      attributed to saturation of hepatic first-pass CYP2D6 metabolism. Thus, at a high
      oral dose, the impact of CYP2D6 metabolism on traxoprodil pharmacokinetics is
      minimal.

PMID- 16984211
TI  - Nanomedicine: clinical applications of polyethylene glycol conjugated proteins
      and drugs.
AB  - The intricate problems associated with the delivery and various unnecessary in
      vivo transitions of proteins and drugs needs to be tackled soon to be able to
      exploit the myriad of putative therapeutics created by the biotechnology boom.
      Nanomedicine is one of the most promising applications of nanotechnology in the
      field of medicine. It has been defined as the monitoring, repair, construction
      and control of human biological systems at the molecular level using engineered
      nanodevices and nanostructures. These nanostructured medicines will eventually
      turn the world of drug delivery upside down. PEGylation (i.e. the attachment of
      polyethylene glycol to proteins and drugs) is an upcoming methodology for drug
      development and it has the potential to revolutionise medicine by drastically
      improving the pharmacokinetic and pharmacodynamic properties of the administered
      drug. This article provides a total strategy for improving the therapeutic
      efficacy of various biotechnological products in drug delivery. This article also
      presents an extensive analysis of most of the PEGylated proteins, peptides and
      drugs, together with extensive clinical data. Nanomedicines and PEGylation, the
      latest offshoots of nanotechnology will definitely pave a way in the field of
      drug delivery where targeted delivery, formulation, in vivo stability and
      retention are the major challenges.

PMID- 16984213
TI  - Pharmacokinetic profile of the somatostatin analogue lanreotide in individuals
      with chronic hepatic insufficiency.
AB  - BACKGROUND AND OBJECTIVES: The somatostatin analogue lanreotide is indicated for
      the treatment of acromegaly and to relieve the symptoms of neuroendocrine
      tumours. The objective of the present study was to compare the pharmacokinetic
      profile and safety of intravenous lanreotide in healthy volunteers and
      individuals with hepatic impairment. METHODS: Immediate-release lanreotide was
      administered at 7 microg/kg during a 20-minute intravenous infusion. Blood
      samples were collected over 24 hours and lanreotide serum levels determined by
      radioimmunoassay. Pharmacokinetic parameters were estimated by non-compartmental
      analyses. RESULTS: Two study centres recruited 53 individuals. Study A comprised
      10 individuals with hepatic insufficiency Child-Pugh grade A (mild), 7 with grade
      B (moderate) and 12 healthy volunteers - all Caucasian. Study B comprised 4
      individuals with hepatic insufficiency Child-Pugh grade A, 6 with grade B, 2 with
      grade C (severe) and 12 healthy volunteers - all Chinese. All participants were
      included in the safety analysis. The pharmacokinetic analysis included all
      participants from study B, but only 12 with hepatic impairment and 11 healthy
      volunteers from study A. Combined analysis of both studies showed an increased
      serum elimination half-life (57%; p < or = 0.001), mean residence time (53%; p <
      or = 0.001) and volume of distribution (at steady state, 57%; at terminal
      disposition phase, 64%; both p < or = 0.001) in individuals with mild hepatic
      insufficiency compared with healthy volunteers. These differences were more
      pronounced in individuals with moderate-to-severe hepatic insufficiency compared
      with healthy volunteers; additionally, the area under the serum concentration
      time curve from time zero to infinity (AUC(infinity)) was increased (23%; p < or
      = 0.05) and clearance (CL) decreased (19%; p < or = 0.05) compared with healthy
      volunteers. The peak serum concentration of lanreotide tended to be lower in
      individuals with hepatic insufficiency than in healthy volunteers (statistically
      non-significant). There were no pharmacokinetic differences between the two
      groups of healthy volunteers. Lanreotide was well tolerated with only two mild
      adverse events that were considered to be possibly related to treatment (both
      nausea and headache with either vomiting or dizziness). There were no clinically
      relevant changes in laboratory parameters or vital signs during the study.
      CONCLUSION: The pharmacokinetic profile of lanreotide depends on the severity of
      hepatic insufficiency with CL and AUC(infinity), which are only slightly altered
      with moderate-to-severe insufficiency. The changes in exposure do not, however,
      require dosage adjustment. Moreover, lanreotide is usually given as a prolonged
      release microparticle or Autogel formulation, and terminal half-life and serum
      concentrations depend on the release properties of the formulation. Dosing is
      also adapted for each patient, based on therapeutic response. Thus, hepatic
      insufficiency does not require additional dosage adjustments.

PMID- 16984214
TI  - Development and evaluation of a generic physiologically based pharmacokinetic
      model for children.
AB  - BACKGROUND: Clinical trials in children are being encouraged by regulatory
      authorities in light of the immense off-label and unlicensed use of drugs in the
      paediatric population. The use of in silico techniques for pharmacokinetic
      prediction will aid in the development of paediatric clinical trials by guiding
      dosing regimens, ensuring efficient blood sampling times, maximising therapeutic
      effect and potentially reducing the number of children required for the study.
      The goal of this study was to extend an existing physiologically based
      pharmacokinetic (PBPK) model for adults to reflect the age-related physiological
      changes in children from birth to 18 years of age and, in conjunction with a
      previously developed age-specific clearance model, to evaluate the accuracy of
      the paediatric PBPK model to predict paediatric plasma profiles. METHODS: The age
      dependence of bodyweight, height, organ weights, blood flows, interstitial space
      and vascular space were taken from the literature. Physiological parameters that
      were used in the PBPK model were checked against literature values to ensure
      consistency. These included cardiac output, portal vein flow, extracellular
      water, total body water, lipid and protein. Five model compounds (paracetamol
      [acetaminophen], alfentanil, morphine, theophylline and levofloxacin) were then
      examined by gathering the plasma concentration-time profiles, volumes of
      distribution and elimination half-lives from different ages of children and
      adults. First, the adult data were used to ensure accurate prediction of
      pharmacokinetic profiles. The model was then scaled to the specific age of
      children in the study, including the scaling of clearance, and the generated
      plasma concentration profiles, volumes of distribution and elimination half-lives
      were compared with literature values. RESULTS: Physiological scaling produced
      highly age-dependent cardiac output, portal vein flow, extracellular water, total
      body water, lipid and protein values that well represented literature data. The
      pharmacokinetic profiles in children for the five compounds were well predicted
      and the trends associated with age were evident. Thus, young neonates had plasma
      concentrations greater than the adults and older children had concentrations less
      than the adults. Eighty-three percent, 97% and 87% of the predicted plasma
      concentrations, volumes of distribution and elimination half-lives, respectively,
      were within 50% of the study reported values. There was no age-dependent bias for
      term neonates to 18 years of age when examining volumes of distribution and
      elimination half-lives. CONCLUSION: This study suggests that the developed
      paediatric PBPK model can be used to scale pharmacokinetics from adults. The
      accurate prediction of pharmacokinetic parameters in children will aid in the
      development of dosing regimens and sampling times, thus increasing the efficiency
      of paediatric clinical trials.

PMID- 16984216
TI  - Optimizing meso-tetra-hydroxyphenyl-chlorin-mediated photodynamic therapy for
      basal cell carcinoma.
AB  - Meso-tetra-hydroxyphenyl-chlorin (mTHPC)-mediated photodynamic therapy (PDT) has
      shown to be effective in the treatment of patients with multiple basal cell
      carcinoma (BCC). In the present study we further optimized the drug-light
      interval and examined the correlation between plasma drug levels and treatment
      efficacy. Thirteen patients with multiple BCC (a total of 366 lesions) were
      included in the study. Following intravenous administration of 0.1 mg kg(-1)
      mTHPC, lesions were illuminated with 10 J cm(-2) light (652 nm, 100 mW cm(-2)) at
      12, 24, 48, 72 or 96 h. Plasma samples were taken prior to each illumination for
      determination of mTHPC levels, and tumor response was evaluated at 6 months and 1
      year. Both univariable and multivariable analyses showed that optimal treatment
      outcome was obtained for a drug-light interval of 24 h when plasma drug levels
      were high. Overall, good cosmetic results with little or no scarring were
      obtained in 87% of the treated lesions and no serious side effects were observed.
      We optimized mTHPC-mediated PDT for patients suffering from multiple BCC by
      determining the most effective drug-light interval and showed that this treatment
      offers significant advantages over surgical resection.

PMID- 16984215
TI  - Prediction of in vivo drug-drug interactions from in vitro data : factors
      affecting prototypic drug-drug interactions involving CYP2C9, CYP2D6 and CYP3A4.
AB  - BACKGROUND: Quantitative predictions of in vivo drug-drug interactions (DDIs)
      resulting from metabolic inhibition are commonly made based upon the inhibitor
      concentration at the enzyme active site [I] and the in vitro inhibition constant
      (K(i)). Previous studies have involved the use of various plasma inhibitor
      concentrations as surrogates for [I] along with K(i) values obtained from
      published literature. Although this approach has resulted in a high proportion of
      successful predictions, a number of falsely predicted interactions are also
      observed. OBJECTIVES: To focus on three issues that may influence the predictive
      value of the [I]/K(i) ratio approach: (i) the use of unbound K(i) (K(i,u)) values
      generated from standardised in vitro experiments compared with literature values;
      (ii) the selection of an appropriate [I]; and (iii) incorporation of the impact
      of intestinal metabolic inhibition for cytochrome P450 (CYP) 3A4 predictions. To
      this end we have selected eight inhibitors of CYP2C9, CYP2D6 and CYP3A4 and 18
      victim drugs from a previous database analysis to allow prediction of 45 clinical
      DDI studies. METHODS: In vitro kinetic and inhibition studies were performed in
      human liver microsomes using prototypic probe substrates of CYP2C9 and CYP2D6,
      with various inhibitors (miconazole, sulfaphenazole, fluconazole, ketoconazole,
      quinidine, fluoxetine, fluvoxamine). The K(i) estimates obtained were corrected
      for non-specific microsomal binding, and the K(i,u) was incorporated into in vivo
      predictions using various [I] values. Predictions for CYP3A4 were based upon in
      vitro data obtained from a previous publication within our laboratory, and an
      assessment of the impact of the interaction in the gut wall is included.
      Predictions were validated against 45 in vivo studies and those within 2-fold of
      the in vivo ratio of area under the plasma concentration-time curve of the
      substrate, in the presence and absence of the inhibitor (AUC(i)/AUC) were
      considered successful. RESULTS: Predictions based upon the average systemic total
      plasma drug concentration ([I](av)) [incorporating the effects of parallel drug
      elimination pathways] and the K(i,u) value resulted in 91% of studies predicted
      to within 2-fold of the in vivo AUC(i)/AUC. This represents a 35% improvement in
      prediction accuracy compared with predictions based upon total K(i) values
      obtained from various published literature sources. A corresponding reduction in
      bias and an increase in precision were also observed compared with the use of
      other [I] surrogates (e.g. the total and new unbound maximum hepatic input plasma
      concentrations). No significant improvement in prediction accuracy was observed
      by incorporating consideration of gut wall inhibition for CYP3A4. CONCLUSION: DDI
      predictions based upon the use of K(i,u) data obtained under a set of optimal
      standardised conditions were significantly improved compared with predictions
      using in vitro data collated from various sources. The use of [I](av) as the [I]
      surrogate generated the most successful predictions as judged by several
      criteria. Incorporation of either plasma protein binding of inhibitor or gut wall
      CYP3A4 inhibition did not result in a general improvement of DDI predictions.

PMID- 16984218
TI  - Emergence of drug resistance is associated with an increased risk of death among
      patients first starting HAART.
AB  - BACKGROUND: The impact of the emergence of drug-resistance mutations on mortality
      is not well characterized in antiretroviral-naive patients first starting highly
      active antiretroviral therapy (HAART). Patients may be able to sustain
      immunologic function with resistant virus, and there is limited evidence that
      reduced sensitivity to antiretrovirals leads to rapid disease progression or
      death. We undertook the present analysis to characterize the determinants of
      mortality in a prospective cohort study with a median of nearly 5 y of follow-up.
      The objective of this study was to determine the impact of the emergence of drug
      resistance mutations on survival among persons initiating HAART. METHODS AND
      FINDINGS: Participants were antiretroviral therapy naive at entry and initiated
      triple combination antiretroviral therapy between August 1, 1996, and September
      30, 1999. Marginal structural modeling was used to address potential confounding
      between time-dependent variables in the Cox proportional hazard regression
      models. In this analysis resistance to any class of drug was considered as a
      binary time-dependent exposure to the risk of death, controlling for the effect
      of other time-dependent confounders. We also considered each separate class of
      mutation as a binary time-dependent exposure, while controlling for the
      presence/absence of other mutations. A total of 207 deaths were identified among
      1,138 participants over the follow-up period, with an all cause mortality rate of
      18.2%. Among the 679 patients with HIV-drug-resistance genotyping done before
      initiating HAART, HIV-drug resistance to any class was observed in 53 (7.8%) of
      the patients. During follow-up, HIV-drug resistance to any class was observed in
      302 (26.5%) participants. Emergence of any resistance was associated with
      mortality (hazard ratio: 1.75 [95% confidence interval: 1.27, 2.43]). When we
      considered each class of resistance separately, persons who exhibited resistance
      to non-nucleoside reverse transcriptase inhibitors had the highest risk:
      mortality rates were 3.02 times higher (95% confidence interval: 1.99, 4.57) for
      these patients than for those who did not exhibit this type of resistance.
      CONCLUSIONS: We demonstrated that emergence of resistance to non-nucleoside
      reverse transcriptase inhibitors was associated with a greater risk of subsequent
      death than was emergence of protease inhibitor resistance. Future research is
      needed to identify the particular subpopulations of men and women at greatest
      risk and to elucidate the impact of resistance over a longer follow-up period.

PMID- 16984219
TI  - In celiac disease, a subset of autoantibodies against transglutaminase binds toll
      like receptor 4 and induces activation of monocytes.
AB  - BACKGROUND: Celiac disease is a small intestine inflammatory disorder with
      multiple organ involvement, sustained by an inappropriate immune response to
      dietary gluten. Anti-transglutaminase antibodies are a typical serological marker
      in patients with active disease, and may disappear during a gluten-free diet
      treatment. Involvement of infectious agents and innate immunity has been
      suggested but never proven. Molecular mimicry is one of the mechanisms that links
      infection and autoimmunity. METHODS AND FINDINGS: In our attempt to clarify the
      pathogenesis of celiac disease, we screened a random peptide library with pooled
      sera of patients affected by active disease after a pre-screening with the sera
      of the same patients on a gluten-free diet. We identified a peptide recognized by
      serum immunoglobulins of patients with active disease, but not by those of
      patients on a gluten-free diet. This peptide shares homology with the rotavirus
      major neutralizing protein VP-7 and with the self-antigens tissue
      transglutaminase, human heat shock protein 60, desmoglein 1, and Toll-like
      receptor 4. We show that antibodies against the peptide affinity-purified from
      the sera of patients with active disease recognize the viral product and self
      antigens in ELISA and Western blot. These antibodies were able to induce
      increased epithelial cell permeability evaluated by transepithelial flux of
      [(3)H] mannitol in the T84 human intestinal epithelial cell line. Finally, the
      purified antibodies induced monocyte activation upon binding Toll-like receptor
      4, evaluated both by surface expression of activation markers and by production
      of pro-inflammatory cytokines. CONCLUSIONS: Our findings show that in active
      celiac disease, a subset of anti-transglutaminase IgA antibodies recognize the
      viral protein VP-7, suggesting a possible involvement of rotavirus infection in
      the pathogenesis of the disease, through a mechanism of molecular mimicry.
      Moreover, such antibodies recognize self-antigens and are functionally active,
      able to increase intestinal permeability and induce monocyte activation. We
      therefore provide evidence for the involvement of innate immunity in the
      pathogenesis of celiac disease through a previously unknown mechanism of
      engagement of Toll-like receptor 4.

PMID- 16984221
TI  - The HIV landscape in a managed care environment: current challenges and potential
      solutions.
AB  - OBJECTIVE: To review the current impact of human immunodeficiency virus (HIV)/
      acquired immunodeficiency syndrome (AIDS) and its treatment on the population and
      on managed care. SUMMARY: In 2006, HIV/AIDS remains as big a problem as ever,
      with many countries reporting an incidence of 40% or higher among intravenous
      drug users. While daunting, this does not detract from the many victories that
      have occurred over the HIV/AIDS landscape. Mortality has declined dramatically
      since 1995. Treatment with highly active antiretroviral therapy (HAART) has been
      simplified and offers substantial survivor benefits. The net effect of these
      advances has been to change the face of HIV/AIDS, from a fatal to a chronic
      illness. Accordingly, current and evolving management strategies need to
      encompass long-term care. CONCLUSION: As people live longer, health care
      management organizations will be looking to balance good outcomes and successful
      long-term care with acceptable costs.

PMID- 16984222
TI  - Successful HIV treatment: lessons learned.
AB  - OBJECTIVE: To review current insights concerning treatment of human
      immunodeficiency virus (HIV). SUMMARY: The range of antiretroviral agents
      available for treating patients who have HIV/AIDS (acquired immunodeficiency
      syndrome) has expanded to 20 medications since the first, zidovudine, was
      approved in 1987. While the exact choice of drugs to use in treatment must be
      tailored to the patient, depending on safety and tolerance, the ultimate goal is
      durable suppression of the HIV virus. Highly active antiretroviral treatment
      (HAART) is the current standard of care and involves treating the patient with a
      combination of antiretrovirals. First-line regimens usually contain a combination
      of 2 nucleoside reverse transcriptase inhibitors plus either one nonnucleoside or
      protease inhibitor. Differences in side effects have become more important than
      differences in efficacy in determining the choice of the initial antiretroviral
      regimen. To prevent the development of viral resistance to treatment, it is
      essential to begin treatment with all medications simultaneously, rather than
      sequentially. If the initial HAART regimen fails, more complex regimens that
      involve adding at least 2 new antiretrovirals can often reestablish control, even
      in patients with extensive pretreatment and in whom there was the development of
      viral resistance. CONCLUSION: For patients with HIV/AIDS embarking on treatment
      today, the durability of HIV suppression in optimal regimens suggests that a
      normal lifespan is now a realistic outcome of HIV treatment.

PMID- 16984220
TI  - Stratus not altocumulus: a new view of the yeast protein interaction network.
AB  - Systems biology approaches can reveal intermediary levels of organization between
      genotype and phenotype that often underlie biological phenomena such as polygenic
      effects and protein dispensability. An important conceptualization is the module,
      which is loosely defined as a cohort of proteins that perform a dedicated
      cellular task. Based on a computational analysis of limited interaction datasets
      in the budding yeast Saccharomyces cerevisiae, it has been suggested that the
      global protein interaction network is segregated such that highly connected
      proteins, called hubs, tend not to link to each other. Moreover, it has been
      suggested that hubs fall into two distinct classes: "party" hubs are co-expressed
      and co-localized with their partners, whereas "date" hubs interact with
      incoherently expressed and diversely localized partners, and thereby cohere
      disparate parts of the global network. This structure may be compared with
      altocumulus clouds, i.e., cotton ball-like structures sparsely connected by thin
      wisps. However, this organization might reflect a small and/or biased sample set
      of interactions. In a multi-validated high-confidence (HC) interaction network,
      assembled from all extant S. cerevisiae interaction data, including recently
      available proteome-wide interaction data and a large set of reliable literature
      derived interactions, we find that hub-hub interactions are not suppressed. In
      fact, the number of interactions a hub has with other hubs is a good predictor of
      whether a hub protein is essential or not. We find that date hubs are neither
      required for network tolerance to node deletion, nor do date hubs have distinct
      biological attributes compared to other hubs. Date and party hubs do not, for
      example, evolve at different rates. Our analysis suggests that the organization
      of global protein interaction network is highly interconnected and hence
      interdependent, more like the continuous dense aggregations of stratus clouds
      than the segregated configuration of altocumulus clouds. If the network is
      configured in a stratus format, cross-talk between proteins is potentially a
      major source of noise. In turn, control of the activity of the most highly
      connected proteins may be vital. Indeed, we find that a fluctuation in steady
      state levels of the most connected proteins is minimized.

PMID- 16984223
TI  - Evidence-based health benefits management: strategies to optimize antiretroviral
      medication adherence and outcomes in HIV/AIDS.
AB  - OBJECTIVE: To review how evidence-based principles can be applied to benefit
      design, specialty network management, and medication therapy management to
      successfully manage pharmaceutical benefits for patients infected with human
      immunodeficiency virus (HIV). SUMMARY: The most critical barrier to successfully
      managing HIV disease is suboptimal patient adherence to antiretroviral therapy.
      Managing HIV infection is unique in that the risk of treatment failure increases
      remarkably with even relatively minor lapses in patient adherence. The
      incremental cost of HIV treatment failure has been approximated at $26,000 per
      patient per year. Treatment failure, of course, also drives mortality related to
      HIV and acquired immunodeficiency syndrome (AIDS). Benefit design, specialty
      medication management strategies, and care management programs can be integrated
      to deliver high-quality, efficient care that optimizes clinical outcomes for
      populations of HIV-infected individuals. CONCLUSION: Managed care programs can be
      structured to provide HIV care that allows optimal patient adherence and clinical
      outcomes.

PMID- 16984224
TI  - Combination of PTEN gene therapy and radiation inhibits the growth of human
      prostate cancer xenografts.
AB  - The resistance of prostate cancers to radiation therapy has been linked to
      abnormalities in overexpression of Bcl-2, an oncogene associated with inhibition
      of apoptosis. In this study, we evaluated whether the combination of the
      overexpression of phosphatase and tensin homolog (PTEN), a protein known to
      inhibit Bcl-2 expression, and radiation therapy would inhibit proliferation of
      Bcl-2-expressing human prostate cancer cells inoculated into the subcutis of
      athymic mice. Compared with either treatment alone, the combination of adenoviral
      vector-expressed PTEN (AdPTEN) and radiation (5 Gy) significantly inhibited
      xenograft tumor growth. Median tumor size on day 48 was 1030 mm3 in untreated
      controls, 656 mm3 in mice treated with radiation (5 Gy) alone, 640 mm3 in mice
      treated with AdPTEN alone, and 253 mm3 in mice treated with the combination
      (p<0.001). Treatment was well tolerated in all cases. Combination treatment also
      enhanced apoptosis (p=0.048), inhibited cellular proliferation (p=0.005), and
      inhibited tumor-induced neovascularity (p=0.030). Interestingly, this treatment
      increased apoptosis not only in tumor cells but also in tumor-associated
      endothelial cells. Together, these findings indicate that AdPTEN strongly
      inhibits the growth of human prostate tumors, especially when combined with
      radiation therapy, and that this effect is mediated by the induction of apoptosis
      and by the inhibition of angiogenesis and cellular proliferation.

PMID- 16984225
TI  - Intraarticular interferon-beta gene therapy ameliorates adjuvant arthritis in
      rats.
AB  - Interferon (IFN)-beta has significant immunomodulatory properties and has
      received much interest as a potentially therapeutic agent for rheumatoid
      arthritis (RA). Systemic IFN-beta treatment of patients with RA was not
      effective, probably because of pharmacokinetic issues. Therefore, we studied the
      effect of local IFN-beta production by adenovirus-mediated gene transfer to the
      ankle joints of arthritic rats. Adjuvant arthritis (AA) in rats was used as a
      model to study intraarticular gene therapy with an adenoviral vector encoding the
      rat IFN-beta gene (Ad.IFN-beta). The effect on paw swelling was measured by water
      displacement plethysmometry. Synovial tissue of the hind paws was examined by
      immunohistochemistry. Bone destruction was analyzed on the basis of radiographs.
      In addition, quantitative real-time polymerase chain reaction was used to assess
      IFN-beta expression. Levels of IFN-beta mRNA and protein peaked 2 days after
      intraarticular injection and declined thereafter. Local delivery of Ad.IFN-beta
      after the onset of disease reduced paw swelling significantly. This was
      accompanied by a reduction in synovial inflammation. The clinical effects in rat
      AA lasted up to 9 days. Strikingly, Ad.IFN-beta treatment protected bone from
      erosion, reduced levels of c-Cbl and Cbl-b (both signaling molecules essential
      for osteoclast activity), and reduced the matrix metalloproteinase-3:tissue
      inhibitor of metalloproteinase-1 ratio in the joint. Immunohistochemical analysis
      of the synovial tissue revealed a clear shift toward a more antiinflammatory
      cytokine profile. Local overexpression of IFN-beta inhibits arthritis progression
      and protects against bone destruction in rat AA. These findings validate IFN-beta
      as a therapeutic molecule for intraarticular gene therapy of arthritis.

PMID- 16984226
TI  - p90 RSK-1 associates with and inhibits neuronal nitric oxide synthase.
AB  - Evidence is presented that RSK1 (ribosomal S6 kinase 1), a downstream target of
      MAPK (mitogen-activated protein kinase), directly phosphorylates nNOS (neuronal
      nitric oxide synthase) on Ser847 in response to mitogens. The phosphorylation
      thus increases greatly following EGF (epidermal growth factor) treatment of rat
      pituitary tumour GH3 cells and is reduced by exposure to the MEK
      (MAPK/extracellular-signal-regulated kinase kinase) inhibitor PD98059.
      Furthermore, it is significantly enhanced by expression of wild-type RSK1 and
      antagonized by kinase-inactive RSK1 or specific reduction of endogenous RSK1. EGF
      treatment of HEK-293 (human embryonic kidney) cells, expressing RSK1 and nNOS,
      led to inhibition of NOS enzyme activity, associated with an increase in
      phosphorylation of nNOS at Ser847, as is also the case in an in vitro assay. In
      addition, these phenomena were significantly blocked by treatment with the RSK
      inhibitor Ro31-8220. Cells expressing mutant nNOS (S847A) proved resistant to
      phosphorylation and decrease of NOS activity. Within minutes of adding EGF to
      transfected cells, RSK1 associated with nNOS and subsequently dissociated
      following more prolonged agonist stimulation. EGF-induced formation of the nNOS
      RSK1 complex was significantly decreased by PD98059 treatment. Treatment with EGF
      further revealed phosphorylation of nNOS on Ser847 in rat hippocampal neurons and
      cerebellar granule cells. This EGF-induced phosphorylation was partially blocked
      by PD98059 and Ro31-8220. Together, these data provide substantial evidence that
      RSK1 associates with and phosphorylates nNOS on Ser847 following mitogen
      stimulation and suggest a novel role for RSK1 in the regulation of nitric oxide
      function in brain.

PMID- 16984227
TI  - Erythropoietic and anti-obesity effects of Garcinia cambogia (bitter kola) in
      Wistar rats.
AB  - The anti-obesity and erythropoietic effects of crude ethanolic extracts of
      Garcinia cambogia (bitter kola) seeds on Wistar rats (Rattus norvegicus) were
      investigated. The rats were divided into three dosage groups: A (0 mg/kg of body
      weight), B (200 mg/kg) and C (400 mg/kg). Weight changes, plasma lipoprotein
      levels and the lipid profile of the liver, gastrointestinal system and adipose
      tissue were monitored as indices for anti-obesity, while the RBC (red blood cell)
      count (assessed by using a haemocytometer) was monitored as a measure of
      erythropoiesis. The extract was administered by gavage for 5 weeks. The results
      for each test group was compared statistically with those for the control
      (P<0.05). Analysis of the results showed a significant increase in RBC counts in
      both test groups and a decrease in weights of experimental animals. There was a
      dose-dependent decrease in the plasma level of very-low-density lipoprotein and a
      dose-dependent increase in the level of chylomicrons. There was a slight, but
      significant, decrease in the level of high-density lipoprotein and a significant
      increase in the level of LDL (low-density lipoprotein). There was significant
      dose-dependent decrease in the TAG (triacylglycerol) pool of adipose tissue and
      the liver of the test groups, but a significant increase in the TAG pool of the
      gastrointestinal system. The increase in the TAG pool of the gastrointestinal
      system is possibly compensatory. The results therefore confirm that ethanolic
      extracts of G. cambogia seeds have both haematologically enhancing and anti
      obesity effects. The decrease in the high-density-lipoprotein level and an
      increase in the LDL level may play an important role in cardiovascular disease.

PMID- 16984228
TI  - SLC41A2 encodes a plasma-membrane Mg2+ transporter.
AB  - The TRPM7 (transient receptor potential melastatin 7) ion channel has been
      implicated in the uptake of Mg2+ into vertebrate cells, as elimination of TRPM7
      expression through gene targeting in DT40 B-lymphocytes renders them unable to
      grow in the absence of supplemental Mg2+. However, a residual capacity of TRPM7
      deficient cells to accumulate Mg2+ and proliferate when provided with
      supplemental Mg2+ suggests the existence of Mg2+ uptake mechanism(s) other than
      TRPM7. Evaluation of the expression of several members of the SLC41 (solute
      carrier family 41) family, which exhibit homology with the MgtE class of
      prokaryotic putative bivalent-cation transporters, demonstrated that one, SLC41A2
      (solute carrier family 41 member 2), is expressed in both wild-type and TRPM7
      deficient DT40 cells. Characterization of heterologously expressed SLC41A2
      protein indicated that it is a plasma-membrane protein with an N-terminus
      outside/C-terminus-inside 11-TM (transmembrane)-span topology, consistent with
      its functioning as a trans-plasma-membrane transporter. In contrast with a
      previous report of ion-channel activity associated with SLC41A2 expression in
      oocytes, investigation of whole cell currents in SLC41A2-expressing DT40 cells
      revealed no novel currents of any type associated with SLC41A2 expression.
      However, expression of SLC41A2 in TRPM7-deficient cells under the control of a
      doxycycline-inducible promoter was able to conditionally enhance their net uptake
      of 26Mg2+ and conditionally and dose-dependently provide them with the capacity
      to grow in the absence of supplemental Mg2+, observations strongly supporting a
      model whereby SLC41A2 directly mediates trans-plasma-membrane Mg2+ transport.
      Overall, our results suggest that SLC41A2 functions as a plasma-membrane Mg2+
      transporter in vertebrate cells.

PMID- 16984229
TI  - The C-terminus of cytochrome b5 confers endoplasmic reticulum specificity by
      preventing spontaneous insertion into membranes.
AB  - The molecular mechanisms that determine the correct subcellular localization of
      proteins targeted to membranes by tail-anchor sequences are poorly defined.
      Previously, we showed that two isoforms of the tung oil tree [Vernicia
      (Aleurites) fordii] tail-anchored Cb5 (cytochrome b5) target specifically to ER
      (endoplasmic reticulum) membranes both in vivo and in vitro [Hwang, Pelitire,
      Henderson, Andrews, Dyer and Mullen (2004) Plant Cell 16, 3002-3019]. In the
      present study, we examine the targeting of various tung Cb5 fusion proteins and
      truncation mutants to purified intracellular membranes in vitro in order to
      assess the importance of the charged CTS (C-terminal sequence) in targeting to
      specific membranes. Removal of the CTS from tung Cb5 proteins resulted in
      efficient binding to both ER and mitochondria. Results from organelle
      competition, liposome-binding and membrane proteolysis experiments demonstrated
      that removal of the CTS results in spontaneous insertion of tung Cb5 proteins
      into lipid bilayers. Our results indicate that the CTSs from plant Cb5 proteins
      provide ER specificity by preventing spontaneous insertion into incorrect
      subcellular membranes.

PMID- 16984230
TI  - TopBP1 contains a transcriptional activation domain suppressed by two adjacent
      BRCT domains.
AB  - TopBP1 has eight BRCT [BRCA1 (breast-cancer susceptibility gene 1) C-terminus]
      domains and is involved in initiating DNA replication, and DNA damage checkpoint
      signalling and repair. Several BRCT-domain-containing proteins involved in
      mediating DNA repair have transcriptional regulatory domains, and as demonstrated
      for BRCA1 these regulatory domains are important in mediating the functions of
      these proteins. These transcriptional regulatory processes involve modification
      of chromatin, and recent evidence has clearly demonstrated that the ability to
      modify chromatin plays an important role in regulating DNA damage signalling and
      repair. Here we report the identification of a TopBP1 transcriptional activation
      domain that is rich in hydrophobic residues, interspersed with acidic amino
      acids, characteristics that are typical of transcriptional activation domains
      identified previously. Two adjacent repressor domains encoded by BRCT2 and BRCT5
      silence this activator and experiments suggest that these repressors actively
      recruit repressor complexes. Both the activator and BRCT2 repressor domains
      function in yeast. The present study identifies several chromatin modification
      domains encoded by TopBP1, and the implications of these findings are discussed
      in the context of the DNA damage response and the understanding of TopBP1
      function.

PMID- 16984231
TI  - Modulation of growth hormone action by sex steroids.
AB  - Growth hormone (GH) is a major regulator of growth, somatic development and body
      composition. Sex steroids can act centrally by regulating GH secretion and
      peripherally modulating GH responsiveness. This review addresses data of
      potential clinical relevance on how sex steroids modulate GH secretion and
      action, aiming to increase the understanding of sex steroid/GH interactions and
      leading to improved management of patients. Sex steroids regulate GH secretion
      directly as well as indirectly through IGF-I modulation. Testosterone stimulates
      GH secretion centrally, an effect dependent on prior aromatization to oestrogen.
      Oestrogen stimulates GH secretion indirectly by reducing IGF-I feedback
      inhibition. Whether oestrogen stimulates GH secretion centrally in females is
      unresolved. Gonadal steroids modify the metabolic effects of GH. Testosterone
      amplifies GH stimulation of IGF-I, sodium retention, substrate metabolism and
      protein anabolism while exhibiting similar but independent actions of its own.
      Oestrogen attenuates GH action by inhibiting GH-regulated endocrine function of
      the liver. This is a concentration-dependent phenomenon that arises invariably
      from oral administration of therapeutic doses of oestrogen, an effect that can be
      avoided by using a parenteral route. This strong modulatory effect of gonadal
      steroids on GH responsiveness provides insights into the biological basis of
      sexual dimorphism in growth, development and body composition and practical
      information for the clinical endocrinologist. It calls for an appraisal of the
      diagnostic criteria for GH deficiency of GH stimulation tests, which currently
      are based on arbitrary cut-offs that do not take into account the shifting
      baseline from the changing gonadal steroid milieu. In the management of GH
      deficiency in the hypopituitary female, oestrogen should be administered by a
      nonoral route. In hypopituitary men, androgens should be replaced concurrently to
      maximize the benefits of GH. In the general population, the metabolic
      consequences of long-term treatment of women with oral oestrogen compounds,
      including selective oestrogen receptor modulators, are largely unknown and
      warrant study.

PMID- 16984232
TI  - Lower ability to oxidize lipids in adult patients with growth hormone (GH)
      deficiency: reversal under GH treatment.
AB  - BACKGROUND: The aim of the study was to characterize lipid oxidation at exercise
      in adults with growth hormone deficiency (GHD) and to evaluate the effect of 6
      and 12 months of GH replacement therapy on substrate carbohydrate (CHO) and lipid
      utilization at exercise. PATIENTS AND MEASUREMENTS: Twenty-five patients with GHD
      and 40 matched controls participated in the study. Ten of the 25 GH-deficient
      patients were treated with recombinant GH for 12 months. Anthropometric
      measurements and exercise calorimetry were performed before and after treatment.
      Maximal fat oxidation and the crossover point [that is the percentage of the
      theoretical maximal power (Wmax th) where CHO become the predominant fuel used
      for oxidation] were determined. RESULTS AND CONCLUSION: The GH-deficient patients
      exhibited a highly significant shift in the balance of substrate oxidation during
      exercise, towards a decrease in fat oxidation, and a shift towards lower
      intensities of the crossover (52 +/- 5.5%vs. 72.6 +/- 6.6% of Wmax th, P < 0.03)
      and maximal fat oxidation (131.04 +/- 14 vs. 234.4 +/- 30.1 mg/min, P < 0.03) in
      the GHD and control groups, respectively. However, GH treatment at 6 and 12
      months partially reversed this defect, resulting in an increase (+83%, P < 0.001)
      in the maximal ability to oxidize fat during exercise. These findings are
      consistent with the hypothesis that a lack of GH reduces the ability to oxidize
      lipids during exercise and that GH treatment restores this muscular metabolic
      property.

PMID- 16984233
TI  - Association of the BTNL2 rs2076530 single nucleotide polymorphism with Graves'
      disease appears to be secondary to DRB1 exon 2 position beta74.
AB  - OBJECTIVE: The HLA region encodes numerous immune response genes, with the DR/DQ
      molecules consistently associated with autoimmune disease (AID). Recent studies
      in sarcoidosis have identified association of a single nucleotide polymorphism
      (SNP) rs2076530 within BTNL2, a potential T-cell inhibitor, independent of the
      known DRB1 association. The aim of this study was to investigate the association
      rs2076530 with disease in a large UK Caucasian Graves' disease (GD) dataset.
      DESIGN: A case control association study of the rs2076530 polymorphism. PATIENTS:
      Eight hundred sixty-four Graves' disease patients and 864 controls. MEASUREMENTS:
      Tests for association with disease. RESULTS: We detected association of rs2076530
      within a large GD dataset [OR = 1.32 (95% CI = 1.14-1.52)], however, linkage
      disequilibrium (LD) analysis revealed association of rs2076530 to be secondary to
      the previously established DRB1 exon 2 encoded position beta74 effect although a
      rare haplotype effect, including both loci, cannot be excluded. CONCLUSIONS:
      BTNL2 may be a sarcoidosis-specific susceptibility loci, although only extensive
      examination of the whole HLA region in different inflammatory/AIDs will enable
      DR/DQ independent HLA effects to be determined.

PMID- 16984234
TI  - Management of amiodarone-induced thyrotoxicosis in Latin America: an electronic
      survey.
AB  - OBJECTIVE: To assess diagnostic and therapeutic approaches to amiodarone-induced
      thyrotoxicosis (AIT) among members of the Latin American Thyroid Society (LATS).
      METHODS: LATS members responded to an online questionnaire that presented an
      index case (a 62-year-old man on amiodarone, with thyrotoxic symptoms and a
      nodular goitre) and a variant (same patient, no goitre). RESULTS: About 25% of
      invited members responded to the questionnaire. Most respondents lived in iodine
      sufficient areas and observed that amiodarone-induced hypothyroidism (AIH) is
      more common than AIT. Nearly all assessed TSH, and the most used combination of
      tests was TSH and free T4 (37%). Thyroid autoimmunity was assessed by about 90%.
      Interleukin-6 (IL-6) was useful to 80%. Additional tests ordered for the index
      case were: radioactive iodine uptake (RAIU; 57%), echo-colour Doppler sonography
      (ECDS; about 50%) and fine-needle aspiration biopsy (FNAB; 44%). For the variant,
      ECDS and RAIU were judged unhelpful by 16%. Most defined the index case as type I
      AIT and the variant as type II AIT, but 16% in LATS suggested a mixed form in the
      index case. As initial treatment, nearly all used thionamides in the index case
      [with potassium perchlorate (KClO(4)) in one-third], while glucocorticoids were
      indicated to the variant by 66%. Only about 5% considered amiodarone withdrawal
      unnecessary. If initial strategy is ineffective in type I AIT, KClO(4) (half) or
      glucocorticoids (a third) are added; in type II, glucocorticoids are indicated by
      most. Once euthyroidism is restored, ablative therapy is prescribed by a third of
      respondents for type I AIT. CONCLUSIONS: There are several points of disagreement
      among thyroidologists regarding AIT management, mainly in the radiological
      evaluation and the approach to the already stabilized patient if amiodarone needs
      to be restarted.

PMID- 16984235
TI  - Short-term suppression of elevated growth hormone concentrations following
      insulin-like growth factor 1 administration in young adults with type 1 diabetes
      does not alter glomerular filtration or albumin excretion rates.
AB  - OBJECTIVE: Young adults with type 1 diabetes mellitus (T1DM) have increased
      glomerular filtration rate (GFR), which may mediate progressive renal disease and
      microalbuminuria. This may be secondary to low concentrations of insulin-like
      growth factor (IGF)-I and GH hypersecretion. We tested the hypothesis that
      restoration of circulating IGF-I concentrations in young adults with T1DM might
      suppress GH secretion, GFR and urinary albumin excretion. DESIGN: In a randomized
      double blind crossover study six young adults with T1DM (three men, 19-24 years)
      received 7 days treatment with rhIGF-I/insulin-like growth factor binding protein
      (IGFBP)-3 complex (SomatoKine) 0.4 mg/kg/day and placebo. Subjects underwent
      overnight insulin infusion for euglycaemia, followed by determination of GFR and
      albumin excretion rate. RESULTS: Following IGF-I/IGFBP-3 complex, overnight
      insulin requirements (0.15 vs placebo 0.21 mU/kg/min, P < 0.04), plasma insulin
      (77 vs placebo 152 pmol/l, P < 0.01) and mean overnight GH (2.6 vs placebo 4.8
      mU/l, P < 0.04) fell. IGF-I (492 vs placebo 218 ng/ml, P < 0.01) and IGFBP-3 (4.5
      vs placebo 3.9 microg/ml, P < 0.05) increased. GFR did not change (145.5 (23.9)
      ml/min/1.73 m(2) post-IGF-I/IGFBP-3 complex vs 152.2 (19.8) post placebo).
      Albumin excretion rate did not change 9.5 (5.5-16.6)mg/24 h pre- vs 11.5 (9.9
      20.2) post-IGF-I/IGFBP-3 complex and 10.7 (8.1-21.2) pre- vs 11.5 (8.7-29.9) post
      placebo. Plasma creatinine levels were lower following IGF-I/IGFBP-3 complex
      (mean +/- SD, 56.2 +/- 16.8 micromol/l) vs placebo (61.5, 45.0, P < 0.02).
      CONCLUSIONS: Seven days treatment with IGF-I/IGFBP-3 complex enhanced overnight
      insulin sensitivity and reduced GH levels, but there was no effect on glomerular
      hyperfiltration or albumin excretion rates.

PMID- 16984236
TI  - Testicular function after 131I therapy for hyperthyroidism.
AB  - OBJECTIVE: Radioiodine-131 is commonly used for treatment of hyperthyroidism but
      there are few available data on the effects of this treatment on male gonadal
      function. The untoward effects of (131)I have been mainly studied in male
      patients treated with high doses for thyroid cancer. In the present work we
      studied the absorbed radiation dose to the testes and testicular function in
      hyperthyroid men after (131)I treatment. PATIENTS AND MEASUREMENTS: Nineteen male
      hyperthyroid patients were enrolled in the study before (131)I therapy. Seventeen
      of the patients had Graves' disease and two had toxic adenoma. The study was
      subdivided into two parts: a dosimetric and a clinical study. Six patients were
      enrolled for the dosimetric study and 13 for the clinical study. The beta dose
      delivered to the testes was evaluated by the Medical Internal Radiation Dose
      (MIRD) method. The gamma dose was measured by thermoluminescent dosimeters (TLDs)
      placed on the skin overlying the inferior poles of the testes for 3 weeks after
      therapy. The clinical evaluation included hormone determination, ultrasound (US)
      of the testes and sperm analysis. Patients were followed up for 12 months after
      (131)I therapy. RESULTS: In the dosimetric study, the beta dose absorbed in the
      testes was 12.5 +/- 8.8 mGy (range 29-15 mGy) and the gamma dose was 15.8 +/- 5.3
      mGy (range 24-11 mGy). The total dose to the testes for administered activity
      unit was 39 +/- 14 microGy/MBq (range 27-86 microGy/MBq). In the clinical study,
      FSH did not change significantly after (131)I treatment for the majority of
      patients. Serum testosterone (T) and the T/LH ratio were significantly reduced 45
      days after treatment and returned to basal levels after 12 months. Ten out of 15
      hyperthyroid patients (67%) had low sperm motility before treatment. A
      significant increase in progressive motility was observed after (131)I therapy
      (Friedman test chi(2) = 12.65, P = 0.01). Conversely, there was no significant
      variation in sperm concentration and percentage of normal forms after (131)I.
      CONCLUSIONS: After (131)I therapy, germinal epithelium and Leydig cell function
      undergo only marginal changes, which may have some significance in subjects with
      a pre-existing fertility impairment.

PMID- 16984237
TI  - The long-term effects of rosiglitazone on serum lipid concentrations and body
      weight.
AB  - OBJECTIVE: Although rosiglitazone, an insulin sensitizer, is known to have
      beneficial effects on high density lipoprotein cholesterol (HDL-C) concentrations
      and low density lipoprotein (LDL) particle size, it has unwanted effects on total
      cholesterol (TC) and LDL cholesterol (LDL-C) concentrations and body weight in
      some short-term studies. The aim of this study was to evaluate the long-term
      effects of rosiglitazone on serum lipid levels and body weight. DESIGN: Open
      labelled clinical study. PATIENTS AND MEASUREMENTS: We prospectively evaluated
      fasting serum glucose, haemoglobin A(1c) (HbA(1c)), lipid profiles and body
      weight at baseline and every 3 months after the use of rosiglitazone (4 mg/day)
      for 18 months in 202 type 2 diabetic patients. RESULTS: TC levels increased
      maximally at 3 months and decreased thereafter. However, overall, TC levels
      remained significantly higher at 18 months than those at baseline. LDL-C levels
      from the 3-month to the 12-month timepoint were significantly higher than those
      at baseline. However, after 15 months, LDL-C concentrations were not
      significantly different from basal LDL-C concentrations. HDL-C levels increased
      after the first 3 months and these levels were maintained. The increment of
      change in HDL-C was more prominent in patients with low basal HDL-C
      concentrations than in patients with high basal HDL-C concentrations. Body weight
      increased after the first 3 months and these levels were maintained. CONCLUSIONS:
      HDL-C and body weight increased and remained elevated for the duration of the
      study. There was an initial increase in LDL-C but this attenuated and by the end
      of the study was not significantly elevated above baseline levels.

PMID- 16984238
TI  - Parity and the metabolic syndrome in older Chinese women: the Guangzhou Biobank
      Cohort Study.
AB  - OBJECTIVE: To examine whether parity or gravidity contributes to the development
      of the metabolic syndrome (MS). METHODS: The first phase of the Guangzhou Biobank
      Cohort Study recruited 7352 women and 3065 men aged 50-93 years in 2003-4. Data
      on the number of live births and pregnancies, other reproduction-associated
      factors and socioeconomic and lifestyles factors were collected by standardized
      interview. The MS components were determined through physical examination and
      measurement of fasting blood samples. MS was identified if waist circumference
      was >or= 90 cm for men or >or= 80 cm for women, plus any two of: (a) raised
      triglyceride (TG) level (1.7 mmol/l) or specific treatment for this lipid
      abnormality; (b) reduced high density lipoprotein (HDL)-cholesterol (< 1.03
      mmol/l in males or < 1.29 mmol/l in females) or specific treatment for this lipid
      abnormality; (c) raised blood pressure (BP, systolic BP >or= 130 mmHg or
      diastolic BP >or= 85 mmHg) or hypertension therapy; and (d) raised fasting
      glucose (>or= 5.6 mmol/l) or previously diagnosed type 2 diabetes. RESULTS:
      Before adjustment for potential confounders, we found associations between the
      number of births and lifestyle and socioeconomic factors in both sexes. However,
      in women, but not in men, body mass index (BMI), waist-hip ratio, triglyceride
      and glucose were positively associated with the number of birth after adjusting
      for a range of potential confounders. The age-adjusted prevalence of the MS
      increased with the number of births and pregnancies in women, but the gradient
      for birth was steeper than that for pregnancies [odds ratio change per birth
      1.16, 95% confidence interval (CI) 1.11-1.22, P < 0.001; odds ratio change per
      pregnancy 1.11, 95% CI 1.06-1.16, P < 0.001], although attenuating the
      association adjustment did not affect the significance of these findings. There
      was no association in men with regard to the number of their partners' live
      births given the same analysis and similar shared living background with the
      women. CONCLUSION: Higher parity or gravidity was associated with a consistent
      increase in the risk of MS in Chinese women. As the association persisted after
      adjustment for lifestyle factors and there was no association between the risk of
      MS and the number of births associated with the partners of the males, the
      association in women may represent a biological response to pregnancy.

PMID- 16984239
TI  - Idiopathic central diabetes insipidus in children and young adults is commonly
      associated with vasopressin-cell antibodies and markers of autoimmunity.
AB  - OBJECTIVES: Autoimmune targeting of hypothalamic-neurohypophyseal structures in
      children and young adults with posterior pituitary and anterior pituitary
      dysfunction, as well as pituitary stalk involvement, are not yet completely
      understood. DESIGN: We aimed to (1) evaluate the presence of circulating
      vasopressin-cell autoantibodies (AVPc-Abs) in young patients with central
      diabetes insipidus (CDI), (2) detect organ-specific autoantibodies as markers of
      autoimmunity, and (3) define the relationship between immune markers and
      neuroimaging findings. PATIENTS: Twenty patients were evaluated at a median age
      of 16.3 years. Twelve patients had idiopathic CDI, six had Langerhans cell
      histiocytosis (LCH) and two had germinoma. AVPc-Abs were evaluated in 40 healthy
      children. Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region
      was performed longitudinally in all subjects. MEASUREMENTS: Circulating arginine
      vasopressin (AVP), protein tyrosine phosphatase (IA2), glutamic acid
      decarboxylase (GAD), 21-hydroxylase (21-OH), endomysium antibodies (EMA),
      parietal cell (PCA), thyroid peroxidase (TPO), thyroglobulin (TG) and TSH
      receptor (TSHr) autoantibodies were evaluated. RESULTS: Circulating AVPc-Abs were
      found in 15 patients (75%), nine with idiopathic CDI, four with LCH and two with
      germinoma; the pituitary stalk was involved in most of them. Five patients with
      idiopathic CDI showed a persistence of AVPc-Abs during follow-up and one became
      positive subsequently. Serum IA2 autoantibodies were demonstrated in 14 patients
      (70%) and 21-OH autoantibodies in three of them. CONCLUSION: In idiopathic CDI,
      circulating AVPc-Abs suggest an autoimmune involvement of the neurohypophyseal
      system. The identification of AVPc-Abs in subjects who could have either
      idiopathic CDI or LCH or germinoma, however, indicates that AVPc-Abs cannot be
      considered a completely reliable marker of autoimmune CDI. Thus, close clinical
      and MRI follow-up are needed because AVPc-Abs may mask germinoma or LCH.

PMID- 16984240
TI  - PROP1 gene analysis in Portuguese patients with combined pituitary hormone
      deficiency.
AB  - OBJECTIVE: Mutations of the PROP1 gene lead to combined pituitary hormone
      deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL
      and, less frequently, ACTH. This study was undertaken to investigate the
      molecular defect in a cohort of patients with CPHD. DESIGN, PATIENTS AND
      MEASUREMENTS: A multicentric study involving 46 cases of CPHD (17 familial cases
      belonging to seven kindreds and 29 sporadic cases) selected on the basis of
      clinical and hormonal evidence of GH deficiency, central hypothyroidism and
      hypogonadotrophic hypogonadism, in the absence of an identified cause of
      hypopituitarism. Mutations of PROP1 were investigated by DNA sequencing.
      Clinical, hormonal and neuroradiological data were collected at each centre.
      RESULTS: PROP1 mutations were identified in all familial cases: five kindreds
      presented a c. 301-302delAG mutation, one kindred presented a c. 358C --> T
      (R120C) mutation and one presented a previously unreported initiation codon
      mutation, c. 2T --> C. Of the 29 sporadic cases, only two (6.9%) presented PROP1
      germline mutations (c. 301-302delAG, in both). Phenotypic variability was
      observed among patients with the same mutations, particularly the presence and
      age of onset of hypocortisolism, the levels of PRL and the results of pituitary
      imaging. One patient presented a sellar mass that persisted into adulthood.
      CONCLUSIONS: This is the first report of a mutation in the initiation codon of
      the PROP1 gene and this further expands the spectrum of known mutations
      responsible for CPHD. The low mutation frequency observed in sporadic cases may
      be due to the involvement of other unidentified acquired or genetic causes.

PMID- 16984241
TI  - Subclinical thyroid dysfunction and blood pressure: a community-based study.
AB  - OBJECTIVE: Overt hypothyroidism and hyperthyroidism are associated with
      hypertension, but it is uncertain whether the same is true of subclinical
      hypothyroidism and hyperthyroidism. DESIGN, SUBJECTS AND MEASUREMENTS: Cross
      sectional study of 2033 participants (aged 17-89 years) in the Busselton Thyroid
      Study who did not have a history of thyroid disease. Systolic blood pressure
      (SBP), diastolic blood pressure (DBP) and the prevalence of hypertension (defined
      as SBP >or=140 mmHg, DBP >or=90 mmHg or on treatment for hypertension) in
      subjects with thyroid dysfunction and euthyroid subjects were compared using
      linear regression models. Subjects with treated hypertension (N = 299) were
      excluded from analyses of SBP and DBP but included in analyses of hypertension
      prevalence. RESULTS: Mean SBP, DBP and the prevalence of hypertension did not
      differ significantly between subjects with subclinical hypothyroidism (N = 105)
      and euthyroid subjects (N = 1859), nor did they differ between subjects with
      serum TSH concentrations in the upper reference range (2.0-4.0 mU/l; N = 418) and
      those with TSH concentrations in the lower reference range (0.4-2.0 mU/l; N =
      1441). The prevalence of hypertension was higher in subjects with subclinical
      hyperthyroidism than euthyroid subjects (prevalence odds ratio 2.8, 95%
      confidence interval 1.3-6.0 adjusted for age, age(2) and sex), but this was based
      on a small number of subjects with subclinical hyperthyroidism (N = 35).
      CONCLUSIONS: Subclinical hypothyroidism is not associated with hypertension. The
      observed association between subclinical hyperthyroidism and hypertension
      requires confirmation in a larger sample.

PMID- 16984242
TI  - Impairment of GH responsiveness to combined GH-releasing hormone and arginine
      administration in adult patients with Prader-Willi syndrome.
AB  - OBJECTIVE: It is unclear if poor health outcomes of adult patients with Prader
      Willi syndrome (PWS) are influenced by GH deficiency (GHD). Few studies have been
      focused on PWS adults, but further information on the concomitant role of obesity
      on GH/IGF-I axis function is needed. The aim of our study was to investigate the
      prevalence of GHD in a large group of adult subjects with genetically confirmed
      PWS. DESIGN AND SUBJECTS: We studied the GH response to a combined administration
      of GHRH (1 microg/kg i.v. at 0 minutes) and arginine (ARG) (30 g i.v., infused
      from 0 to 30 minutes) as well as the baseline IGF-I levels, in a group of 44 PWS
      adults (18 males, 26 females) aged 18-41.1 years. The same protocol was carried
      out in a control group of 17 obese subjects (7 males, 10 females) aged 21.8-45.8
      years. MEASUREMENTS: Blood samples were taken at -15 and 0 minutes and then 30,
      45, 60, 90 and 120 minutes after GHRH administration. Serum GH and total IGF-I
      concentrations were measured by chemioluminescence. Statistical analysis was
      performed by Student's t-test for unpaired data, and using analysis of variance
      for parametric and nonparametric (Mann-Whitney test) data, where appropriate. The
      relationship between pairs of variables was assessed by Pearson's correlation.
      Independent variables influencing GH secretion were tested by multiple linear
      regression analysis. RESULTS: The GH response to GHRH + ARG was significantly
      lower in PWS patients (GH peak (mean +/- SE) 8.4 +/- 1.2 microg/l; AUC: 471.4 +/-
      77.8 microg/l/h) than obese subjects (GH peak 15.7 +/- 2.9 microg/l, P < 0.02;
      AUC 956 +/- 182.9 microg/l/h, P < 0.005). When considered individually, 17 of 44
      PWS individuals (38.6%) were severely GHD, according to the cut-off limit of 4.1
      microg/l for obese individuals, and low IGF-I-values were present in 33 PWS
      patients. Moreover, impaired GH response was combined with subnormal IGF-I levels
      in all PWS patients with GHD. CONCLUSIONS: Adult subjects with PWS had a reduced
      responsiveness to GHRH + ARG administration associated with reduced IGF-I levels.
      In addition, a severe GHD for age was demonstrated in a significant percentage of
      PWS subjects. These findings are in agreement with the hypothesis that a complex
      derangement of hypothalamus-pituitary axis occurred in PWS, and suggested that
      impaired GH secretion is not an artefact of obesity.

PMID- 16984243
TI  - Disparities between male and female patients with thyroid cancers: sex difference
      or gender divide?
AB  - OBJECTIVE: This investigation was undertaken to quantify histopathological
      disparities between male and female patients with sporadic and hereditary thyroid
      cancers, which may reflect a biological 'sex difference' or a behavioural 'gender
      divide'. DESIGN: Retrospective cohort analysis (November 1994-January 2006).
      PATIENTS: 1298 Consecutive surgical patients with sporadic papillary (n = 587),
      sporadic follicular (n = 232), sporadic medullary (n = 320), and hereditary
      medullary thyroid cancers (n = 159) from a tertiary referral centre.
      MEASUREMENTS: Age at diagnosis of cancer, primary tumour diameter, frequency of
      extrathyroidal extension, lymph node and distant metastases, and cancer subtypes.
      RESULTS: Primary diameters of sporadic tumour entities (papillary, 26.0 vs. 19.3
      mm; follicular, 54.9 vs. 35.1 mm; and medullary, 27.9 vs. 20.8 mm), but not
      hereditary medullary cancers, were significantly (P <or= 0.001) larger in male
      patients. Likewise, lymph node metastases from sporadic papillary cancers (60%vs.
      44%, P < 0.001), the insular subtype in sporadic follicular cancers (22%vs. 8%, P
      = 0.003), extrathyroidal extension of sporadic medullary cancers (35%vs. 15%, P <
      0.001), and distant metastases from sporadic medullary cancers at the most recent
      operation (29%vs. 15%, P = 0.002) were seen significantly more often with male
      patients. No significant differences were observed between male and female
      patients with hereditary medullary cancers, half of which were detected by
      screening. CONCLUSIONS: Our data emphasize the need for earlier diagnosis and
      intervention in male patients to ensure that male sex will cease sometime to
      constitute an ominous prognostic marker of advanced thyroid cancer.

PMID- 16984244
TI  - Sex-specific association of the androgen to oestrogen ratio with adipocytokine
      levels in older adults: the Rancho Bernardo Study.
AB  - OBJECTIVE: Androgens and oestrogens have opposing effects on some adipocyte
      functions. Thus, the androgen to oestrogen balance may be as important as the
      individual hormones in determining the biological interaction between endogenous
      sex hormones and adipocyte-derived factors such as adiponectin and leptin. We
      tested this hypothesis by evaluating the sex-specific, cross-sectional
      association of sex hormones and androgen to oestrogen ratios with serum
      adiponectin and leptin in older men and postmenopausal women. DESIGN: Cross
      sectional. PARTICIPANTS: A total of 1510 community dwelling men and
      postmenopausal women aged 50-92 years. MEASUREMENTS: Serum leptin, adiponectin
      and sex hormone levels. RESULTS: Adiponectin and leptin levels were higher in
      women than men (P < 0.001). In both sexes, adiponectin concentrations were lower,
      and leptin levels higher, with increasing BMI and waist girth (all P < 0.001).
      Although the ratio of total testosterone to total oestradiol was significantly
      associated with both adipocytokines in both sexes, the strongest and most
      consistent hormone-adipocytokine associations were observed when the androgen to
      oestrogen ratio was expressed as total testosterone to bioavailable oestradiol.
      In linear regressions, the testosterone to bioavailable oestradiol ratio was
      positively related to adiponectin and inversely related to leptin, with nearly
      identical standardized beta-coefficients for men and women (all P < 0.001). The
      strength of the hormone ratio-adipocytokine associations was reduced, but not
      eliminated, after adjustment for age, adiposity and cardiovascular disease risk
      factors, including insulin resistance. CONCLUSIONS: The striking similarity of
      the hormone ratio-adipocytokine associations for men and women, despite wide
      differences in sex hormone and adipocytokine levels, suggests these results
      reflect underlying physiological mechanisms common to both sexes.

PMID- 16984245
TI  - Prevalence and prediction of malignancy in cytologically indeterminate thyroid
      nodules.
AB  - OBJECTIVE: Controversy surrounds the evaluation of nodules with indeterminate
      cytology results. Malignancy rates in these nodules are not low. We examined the
      malignancy rates in nodules that showed follicular neoplasm or atypical cells on
      cytology and attempted to predict malignancy based on ultrasonographic features.
      DESIGN AND PATIENTS: We retrospectively analysed 5 years' cytopathology results
      of fine-needle aspiration biopsy (FNAB) specimens of indeterminate follicular
      thyroid lesions prior to thyroidectomy. The prevalence of malignancy on final
      histology was determined. The sonographic features of the thyroid nodules with
      respect to size, echogenicity, echo structure, border shape and presence of
      calcification were analysed. RESULTS: A total of 86 patients (15 men, 61 women;
      mean age 52.1 +/- 12.5 years) with indeterminate cytology underwent thyroidectomy
      and had histopathological diagnoses. The average nodule was 18.9 +/- 12.3 mm. The
      prevalence of malignancy in patients with atypical cell cytology was 51.7% (30 of
      59), and the prevalence of malignancy in patients with follicular neoplasm
      cytology was 15% (4 of 27). Malignancy prevalence was higher in patients who had
      follicular neoplasm cytology with atypical cells than in those without atypical
      cells (2 of 7 and 2 of 20, respectively). We found no significant correlations
      between sonographic or clinical features and malignancy in this patient group.
      Sonographic features and nodule size are not useful predictors of malignancy.
      CONCLUSION: Until better molecular markers for malignancy are developed, surgical
      consultation remains necessary after examination of cytologically indeterminate
      FNAB specimens in patients with follicular thyroid lesions. But in follicular
      lesions without atypical cells the malignancy rate is low and reassessment later
      on could be an alternative approach.

PMID- 16984246
TI  - Comparison of iodine uptake in tumour and nontumour tissue under thyroid hormone
      deprivation and with recombinant human thyrotropin in thyroid cancer patients.
AB  - AIM: Recombinant human thyrotropin (rhTSH) is a new option for diagnostic follow
      up in patients with differentiated thyroid cancer (DTC). Iodine kinetics after
      administration of rhTSH is controversially discussed. The aim of our study was to
      compare the time course of radioiodine in tumour and normal tissue during periods
      of TSH elevation in patients in a hypothyroid state (HS) following hormone
      withdrawal, with those under euthyroidism (ES) after the administration of rhTSH.
      PATIENTS AND METHODS: We investigated four patients who had undergone near-total
      thyroidectomy and were suffering from metastatic disease. Dosimetric calculations
      were performed using tumour and whole-body uptake, and background measurements
      from 123-iodine scans performed 0, 4, 24 and 48 h after the application of
      (123)I. RESULTS: All patients had lesser uptake of (123)I under rhTSH stimulation
      than after hormone withdrawal. The median maximum TG (thyroglobulin) levels were
      733.1 ng/ml with HS and 548.0 ng/ml with ES. The median half-life in tumour
      tissue was 39.8 h (mean 65.9, range 11.5-194.0) with HS and 21.9 h (mean 38.7,
      range. 8.7-113.9) with ES. The median uptake dose in per cent in tumour tissue
      was 0.08 (mean 0.15, range 0.04-0.6) with HS and 0.05 (mean 0.08, range 0.03-0.2)
      with ES. Furthermore, the cumulative activity in metastatic tissue was lower
      after rhTSH than during hypothyroidism, with considerable variations between
      individual lesions. CONCLUSION: In our small group of DTC patients with
      metastatic disease, the effectiveness of radioiodine therapy following rhTSH was
      anticipated to be less than that in individuals who were hypothyroid after
      levothyroxine (L-T(4)) withdrawal. Endogenous TSH stimulation of metastatic
      thyroid cancer with radioiodine should not be performed without prior target
      tumour lesion dosimetry with (123)I.

PMID- 16984247
TI  - Do the limits of serum prolactin in disconnection hyperprolactinaemia need re
      definition? A study of 226 patients with histologically verified non-functioning
      pituitary macroadenoma.
AB  - BACKGROUND: The differentiation of a pituitary non-functioning macroadenoma from
      a macroprolactinoma is important for planning appropriate therapy. Serum PRL
      levels have been suggested as a useful diagnostic indicator. However, values
      between 2500 and 8000 mU/l are a grey area and are currently associated with
      diagnostic uncertainty. OBJECTIVE: We wished therefore, to investigate the serum
      PRL values in a large series of patients presenting with apparently non
      functioning pituitary macroadenomas. PATIENTS AND METHODS: All patients
      presenting to the Department of Endocrinology in Oxford with clinically non
      functioning pituitary macroadenomas (later histologically verified) between 1990
      and 2005 were studied. Information documented in the notes on the medications and
      on the presence of conditions capable of affecting the serum PRL levels at the
      time of blood sampling was also collected. RESULTS: Two hundred and twenty-six
      patients were identified (median age at diagnosis 55 years, range 18-88 years;
      146 males/80 females; 143 gonadotroph, 46 null cell, 25 plurihormonal and 12
      silent ACTH adenomas). All tumours had suprasellar extension. At the time of
      blood sampling 41 subjects were taking medications capable of increasing serum
      PRL. Hyperprolactinaemia was found in 38.5% (87/226) of the patients. The median
      serum PRL values in the total group were 386 mU/l (range 16-3257) (males: median
      299 mU/l, range 16-1560; females: median 572 mU/l, range 20-3257) and in those
      not taking drugs capable of increasing serum PRL 363 mU/l (range 16-2565) (males:
      median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-2565). Serum
      PRL < 2000 mU/l was found in 98.7% (223/226) of the total group and in 99.5%
      (184/185) of those not taking drugs. Among the three subjects with serum PRL >
      2000 mU/l, two were taking oestrogen preparations. CONCLUSIONS: Based on a large
      series of histologically confirmed cases, serum PRL > 2000 mU/l is almost never
      encountered in nonfunctioning pituitary macroadenomas. Values above this limit in
      the presence of a macroadenoma should not be surrounded by diagnostic uncertainty
      (after acromegaly or Cushing's disease have been excluded); a prolactinoma is the
      most likely diagnosis and a dopamine agonist should be considered as the
      treatment of choice.

PMID- 16984248
TI  - Adiponectin levels and cardiovascular risk factors in hypothyroidism and
      hyperthyroidism.
AB  - OBJECTIVE: Adiponectin, an adipose tissue-derived hormone, has been reported to
      have anti-inflammatory and anti-atherogenic effects. The physiological effect of
      adiponectin on the metabolic changes and its relation with cardiovascular risk
      factors in thyroid dysfunction states is still not clear. The aim of the study
      was to evaluate plasma adiponectin level and its relation to cardiovascular risk
      factors in patients with thyroid dysfunction. PATIENTS AND MEASUREMENTS: Sixty
      seven patients with hypothyroidism, 56 patients with hyperthyroidism and 52 age-
      and sex-matched euthyroid subjects were enrolled in the study. Adiponectin, C
      reactive protein (CRP), homocysteine (Hcy), lipid parameters, Lipoprotein(a) [Lp
      (a)], Apolipoprotein (Apo) A, Apo B and fibrinogen levels were measured in all
      subjects. Insulin sensitivity was determined using the Homeostasis Model
      Assessment (HOMA-IR). RESULTS: Circulating adiponectin levels were not different
      between the groups (16.2 +/- 5.0, 15.1 +/- 3.7, 15.9 +/- 4.8 ng/ml; hypothyroid,
      hyperthyroid, euthyroid group, respectively). Plasma adiponectin levels
      correlated negatively with body mass index (BMI) and HOMA-IR index and positively
      with high-density lipoprotein cholesterol (HDL-C) in all groups. There was a
      significant correlation between adiponectin and CRP levels in both hypothyroid
      and hyperthyroid groups. In all groups, adiponectin levels did not correlate with
      age, systolic blood pressure, diastolic blood pressure and thyroid hormones.
      Multiple regression analysis revealed BMI and HDL-C levels to be the most
      important predictors of circulating adiponectin levels. CONCLUSIONS: Plasma
      adiponectin levels are associated with BMI and HDL-C levels in patients with
      hypothyroidism and hyperthyroidism. But there is not a direct relation of
      adiponectin with thyroid hormones in these patients.

PMID- 16984249
TI  - Pituitary tumour transforming gene (PTTG) expression correlates with the
      proliferative activity and recurrence status of pituitary adenomas: a clinical
      and immunohistochemical study.
AB  - BACKGROUND: The pituitary tumour transforming gene (pttg) plays a central role in
      pituitary tumorigenesis, but PTTG protein expression is poorly documented and its
      relationship with tumour cell proliferation and the prognosis of pituitary
      adenomas is unclear. AIM: The aim of this study was to evaluate the
      immunohistochemical expression of PTTG and Ki-67 in 45 human pituitary adenomas
      according to the tumour histotype, aggressiveness and persistence/recurrence
      status. PATIENTS AND METHODS: The tumours comprised 37 macroadenomas and 8
      microadenomas. Twenty patients experienced disease persistence or recurrence
      after transsphenoidal surgery. Disease recurrence was observed in 16 patients, 8
      72 months after surgery. RESULTS: No PTTG or Ki-67 expression was detected in
      normal pituitary tissue. In pituitary adenomas, tumour nuclei were positive for
      PTTG and Ki-67 in 89 and 98% of samples, respectively, and there was a strong
      correlation between the expression of the two proteins (P < 0.001). By the ROC
      curves method, a PTTG score of 3.3% was the best cut-off for distinguishing
      between recurrent and nonrecurrent pituitary adenomas (P < 0.05; sensitivity 60%;
      specificity 76%). A 2.9% cut-off was obtained for both PTTG (P < 0.01;
      sensitivity 77%; specificity 71%) and Ki-67 (P < 0.05; sensitivity 85%;
      specificity 64%) among patients with more than 1 year of follow-up. Neither PTTG
      nor Ki-67 expression was influenced by the maximal tumour diameter, tumour grade,
      age, gender or presurgical medical treatment. Both PTTG and Ki-67 tumour score >
      2.9% identified a subgroup of patients with a significantly higher recurrence
      free interval (P < 0.01). By multivariate analysis, a > 2.9% Ki-67 tumour score
      was the best predictor of pituitary tumour persistence/recurrence after surgery
      (chi(2) = 8.2, P < 0.01). CONCLUSION: PTTG is expressed in approximately 90% of
      pituitary tumours of different histotypes but with a high variability from one
      case to another. As expected, PTTG expression parallels that of Ki-67 and both
      are correlated to a more aggressive behaviour. However, a 2.9% Ki-67 cut-off
      proved to be the most reliable biological marker for predicting the recurrence
      potential of these tumours, when an adequate postsurgical follow-up is
      considered.

PMID- 16984250
TI  - The sodium-iodide symporter expression in placental tissue at different
      gestational age: an immunohistochemical study.
AB  - BACKGROUND: Iodide (I(-)) is crucial for foetal thyroid function. Foetal iodide
      results from maternal circulating iodide and from deiodination of iodothyronines
      within the placenta. The Na(+)/I(-) symporter (NIS) localized in placental cells
      appears to be involved in iodide exchange. Low NIS expression has been reported
      in trophoblast cells from the first trimester and pregnancy at term. AIMS: The
      aim of this study was to examine NIS expression by immunohistochemistry in the
      major components of human ovular tissue and placenta. MATERIALS AND METHODS:
      Formalin-fixed and paraffin-embedded specimens of placental tissue from the first
      trimester and at term were analysed. NIS expression was quantified as percentage
      of NIS-positive cells/total cells. NIS expression was also evaluated by real-time
      polymerase chain reaction (RT-PCR) in five first-trimester and five at-term
      placental specimens. RESULTS: In the first-trimester specimens heterogeneous NIS
      immunoreactivity was found in cyto-syncytiotrophoblast cells, with a range of NIS
      positive cells from 5% to 80% (mean +/- SD 21.85 +/- 23.95), in mesenchymal and
      endothelial cells from 1% to 40% (14.5 +/- 11.16), in decidual cells from 5% to
      40% (10.38 +/- 11.98) and in endometrial glands from 3% to 40% (21.86 +/- 13.93).
      In specimens from placenta at term, NIS-positive cyto-syncytiotrophoblast cells
      were between 5% and 40% (mean 17.85 +/- 18.15), mesenchymal and endothelial cells
      between 1% and 40% (13.67 +/- 12.16), decidual tissue between 5% and 30% (16.43
      +/- 9.08), and endometrial glands between 3% and 40% (16.67 +/- 15.27). No
      significant differences in NIS expression were observed between the first
      trimester and placenta at term. A similar level of mRNA expression for the NIS
      gene was obtained by RT-PCR both in ovular material of the first trimester and in
      placenta at term. CONCLUSIONS: We found NIS to be expressed in various placental
      and ovular components and its expression to remain constant during pregnancy.

PMID- 16984251
TI  - Secondary adrenal failure due to long-term treatment with flunitrazepam.

PMID- 16984252
TI  - Authors' response: association of HLA DQ4-DR8 haplotype with papillary thyroid
      carcinomas.

PMID- 16984253
TI  - Short-term dexamethasone administration does not alter serum adiponectin or
      resistin concentrations in overweight and obese subjects despite an increase in
      insulin resistance.

PMID- 16984254
TI  - Antitumour effects of temozolomide in a man with a large, invasive prolactin
      producing pituitary neoplasm.

PMID- 16984256
TI  - Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin
      peptides adrenocorticotropin and alpha-melanocyte-stimulating hormone in the
      skin.
AB  - The neuroendocrine precursor protein proopiomelanocortin (POMC) and its derived
      neuropeptides are involved in a number of important regulatory processes in the
      central nervous system as well as in peripheral tissues. Despite its important
      role in controlling the local activation of melanocortin (MC) receptors, the
      extracellular proteolytic processing of POMC peptides has received little
      attention. The mechanisms relevant for controlling the bioavailability of
      adrenocorticotropin and melanocyte-stimulating hormones for the corresponding MC
      receptors in the skin by specific peptidases such as neprilysin (neutral
      endopeptidase; NEP) or angiotensin-converting enzyme (ACE) have been addressed in
      a number of recent investigations. This review summarizes the current body of
      knowledge concerning the qualitative and quantitative POMC peptide processing
      with respect to the action and specificity of NEP and ACE and discusses relevant
      recent analytical methodologies.

PMID- 16984257
TI  - Expression of keratinocyte growth factor and its receptor in clear cell
      acanthoma.
AB  - The aetiopathogenic mechanism underlying clear cell acanthoma (CCA) is not
      completely clear and it has been postulated that CCA and psoriasis may have a
      similar pathogenesis because of the common features shared by the two diseases.
      As it has been recently demonstrated that in psoriatic lesions the paracrine
      epithelial growth factors [keratinocyte growth factor (KGF)/fibroblast growth
      factor (FGF)-7 and FGF-10] are involved in promoting and sustaining the
      keratinocyte hyperproliferation, the aim of this study was to analyse the
      expression of KGF on CCA lesions and to search for a role of this growth factor
      in CCA pathogenesis. Immunohistochemical analysis showed an up-modulation of KGF
      in CCA, although the immunostaining was variable among the different samples
      collected. Positive immunoreactivity for KGF was detected mainly on dermal areas
      where the inflammatory infiltrate was more pronounced suggesting a relationship
      between lymphocyte activation and KGF up-modulation. Real-time quantitative RT
      PCR assay performed on mRNA extracted from formalin-fixed paraffin-embedded CCA
      and normal skin (NS) samples further demonstrated the overexpression of the
      KGF/FGF-7 gene in all CCA samples compared with NS. Moreover, the evaluation by
      immunohistochemistry of KGF receptor distribution, the high-affinity tyrosine
      kinase receptor for KGF, showed a down-modulation of this receptor, as previously
      reported in the presence of increased levels of KGF. Taken together these results
      suggest the inflammatory nature of CCA and further support the hypothesis that
      this disease may represent, like psoriasis, an inflammatory dermatosis in which
      KGF up-modulation may be responsible for keratinocyte hyperproliferation and may
      represent a new common feature of both diseases.

PMID- 16984258
TI  - Activation of platelet-activating factor receptor in SZ95 sebocytes results in
      inflammatory cytokine and prostaglandin E2 production.
AB  - Platelet-activating factor (PAF) is a group of phosphocholines with various
      biological effects mediated by the PAF receptor (PAF-R). Activation of the
      epidermal PAF-R induces the expression of inflammatory mediators, including
      cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). The upregulation of COX
      2 expression has been shown to be involved in sebocyte proliferation, sebaceous
      gland inflammation and carcinogenesis. The present study was designed to
      investigate whether PAF-R activation could induce the expression of COX-2 and
      production of PGE(2), as well as secretion of the inflammatory cytokine,
      interleukin-8 (IL-8), in the immortalized sebaceous gland cell line SZ95. Using
      calcium mobilization studies, we first confirmed that PAF can signal through PAF
      R in SZ95 sebocytes. We then found that the production of IL-8 was induced
      following treatment with PAF-R agonist, however blocked by a specific PAF-R
      antagonist. Induction of COX-2 expression and increased PGE(2) production were
      observed in SZ95 sebocytes after PAF-R activation. Finally, it was demonstrated
      that the production of PGE(2), induced by PAF-R activation and mediated by COX-2
      expression, was blocked following PAF-R antagonism in SZ95 sebocytes. These
      studies suggest that SZ95 sebocytes express functional PAF-Rs and PAF-Rs are
      involved in regulating the expression of inflammatory mediators, including COX-2,
      PGE(2) and IL-8.

PMID- 16984259
TI  - MMP-21 is expressed by macrophages and fibroblasts in vivo and in culture.
AB  - Matrix metalloproteinase (MMP)-21 and MMP-26 (matrilysin-2) are two recently
      cloned epithelial metalloproteases. Here we examined their expression in various
      benign skin disorders, in which macrophages and fibroblasts have been implicated
      as well as in cultures of these cells. Expression of MMP-21 was detected by
      immunohistochemistry in a subset of macrophages of granulomatous skin lesions and
      in fibroblasts in dermatofibromas. MMP-21 mRNA was found in THP-1, U937, HEL 299
      and Hs68 cells. Furthermore, MMP-21 protein was detected by immunohistochemistry
      in cultures of the same cell lines. In culture MMP-21 was upregulated by phorbol
      myristate acetate in THP-1 cells and by retinoic acid (RA) in U937 cells, and
      downregulated by transforming growth factor beta 1 (TGF-beta1) in HEL 299 as
      assessed by Taqman quantitative polymerase chain reaction (PCR). Expression of
      MMP-26 was detected by immunohistochemistry in granulomatous skin diseases and
      actinic elastosis. MMP-26 at both mRNA and protein levels was only found in HEL
      299 cells. In culture it was downregulated by TGF-beta1, RA and IL-1beta as
      assessed by Taqman quantitative PCR. Our results suggest these two novel MMPs are
      not only associated with cancer but may be important in connective tissue
      remodelling and pathobiology of various benign skin disorders.

PMID- 16984260
TI  - Influence of interleukin-1alpha on androgen receptor expression and cytokine
      secretion by cultured human dermal papilla cells.
AB  - Dermal papilla cells (DPC) control the growth character of the hair follicle
      through their elaboration of mitogenic factors and extracellular matrix
      components. Further, the dermal papilla is a primary site of androgen action in
      the hair follicle. Interleukin-1alpha (IL-1alpha) is prominent in skin wounding
      and inflammatory responses although regarded as a negative hair growth regulator.
      We studied the effect of IL-1alpha and the potent androgen 5alpha
      dihydrotestosterone (DHT) on the expression of the androgen receptor (AR) and
      various factors secreted by cultured human temporal scalp DPC. IL-1alpha
      triggered cellular changes consistent with nuclear factor-kappaB pathway
      activation as well as reduced AR mRNA and protein expression levels for DHT
      stimulated DPC. This cytokine also increased DPC supernatant keratinocyte growth
      factor (KGF), vascular endothelial growth factor (VEGF), IL-8 and granulocyte
      macrophage colony-stimulating factor (GM-CSF) concentrations. IL-1alpha did not
      influence DPC supernatant levels of transforming growth factor-beta1, a negative
      hair growth regulator. The stimulatory effect of IL-1alpha on DPC VEGF, GM-CSF,
      KGF, and IL-8 expression was also evident at the mRNA level for these cytokines.
      IL-1alpha also increased mRNA transcript levels of protease-nexin-1, a secreted
      serine protease inhibitor expressed in the dermal papilla of anagen-stage hair
      follicles. Although DHT did not affect supernatant cytokine concentrations, the
      androgen altered mRNA transcript levels of several factors for DPC co-stimulated
      with IL-1alpha. In consideration of its in vitro activity profile, IL-1alpha may
      be an important modifier of dermal papilla activity as well as potentially
      influence androgen-regulated gene expression in DPC.

PMID- 16984261
TI  - Towards the development of a pragmatic technique for isolating and
      differentiating nestin-positive cells from human scalp skin into neuronal and
      glial cell populations: generating neurons from human skin?
AB  - Nestin+ hair follicle-associated cells of murine skin can be isolated and
      differentiated in vitro into neuronal and glial cells. Therefore, we have asked
      whether human skin also contains nestin+ cells, and whether these can be
      differentiated in vitro into neuronal and/or glial cell populations. In this
      methodological pilot study, we show that both are indeed the case - employing
      purposely only very simple techniques for isolating, propagating, and
      differentiating nestin+ cells from normal human scalp skin and its appendages
      that do not require selective microdissection and tissue compartment isolation
      prior to cell culture. We show that, it is in principle, possible to maintain and
      propagate human skin nestin+ cells for extended passage numbers and to
      differentiate them into both neuronal (i.e. neurofilament+ and/or PGP9.5+) and
      glial (i.e. GFAP+, MBP+ and/or O4+) cell populations. Therefore, human scalp skin
      can serve as a highly accessible, abundant, and convenient source for autologous
      adult stem cell-like cells that offer themselves to be exploited for
      neuroregenerative medicine purposes.

PMID- 16984262
TI  - Increased permeability for polyethylene glycols through skin compromised by
      sodium lauryl sulphate.
AB  - In this in vivo human study we assessed the influence of skin damage by sodium
      lauryl sulphate (SLS) on percutaneous penetration of polyethylene glycols (PEGs)
      of different molecular weights (MW). Percutaneous penetration of PEGs was
      determined using tape stripping of the stratum corneum (SC). The forearm skin of
      volunteers was pretreated with 5% w/w SLS for 4 h, and 24 h later patches with
      PEGs were applied for 6 h. The penetration parameters were deduced by data
      regression to Fick's law for unsteady-state diffusion. The trans-epidermal water
      loss (TEWL) increased after SLS treatment from 6.3 +/- 2.1 to 17.9 +/- 8.7
      g/m(2)/h. The diffusion coefficient for all PEGs was increased in the SLS-damaged
      skin. The increase was smaller for higher MW. In addition, the partition
      coefficient of PEGs between SC and water was larger in the SLS-compromised skin
      and showed a tendency to increase with MW. The permeability coefficient decreased
      gradually with increasing MW of PEGs in both control and SLS-compromised skin.
      SLS caused a threefold increase in the permeability coefficient for all MWs
      ranging in control skin from 0.34 to 0.70 x 10(-5) cm/h and in the SLS
      compromised skin from 1.20 to 2.09 x 10(-5) cm/h for MW of 590-282 Da. The
      results of this study show the deleterious effect of SLS on the skin barrier for
      hydrophilic PEGs. A defective skin barrier will facilitate absorption of other
      chemicals and local skin effects.

PMID- 16984263
TI  - Expression of chitinase-like proteins in the skin of chronic proliferative
      dermatitis (cpdm/cpdm) mice.
AB  - Mammalian chitinase-like proteins belong to a family of proteins structurally
      related to chitinases but devoid of enzymatic activity. They have a postulated
      role in remodeling of extracellular matrix and defense mechanisms against chitin
      containing pathogens. The expression of these proteins is increased in parasitic
      infections and allergic airway disease, but their expression in dermatitis has
      not been examined. The mRNA expression of two chitinase 3-like (Chi3L) proteins,
      Chi3L3 (Ym1) and Chi3L4 (Ym2), was determined in the skin of normal mice, chronic
      proliferative dermatitis (cpdm/cpdm) mutant mice and mice with experimentally
      induced contact hypersensitivity reaction. The localization of Chi3L3 and Chi3L4
      proteins in cells was determined by fluorescence microscopy of double-labeled
      frozen sections of skin, and confirmed in vitro by stimulation of macrophages and
      mast cells with cytokines. Quantitative RT-PCR demonstrated a 976-fold increase
      of Chi3l4 mRNA expression and a 24-fold increase of Chi3l3 mRNA expression in the
      skin of cpdm/cpdm mice. Their expression was also increased in the ears of mice
      with 2,4-dinitrofluorobenzene-induced contact hypersensitivity, but the increase
      was greater for Chi3l3 mRNA (51-fold) than Chi3l4 mRNA (32-fold). Western blot
      analysis with an antibody against Chi3L3 and Chi3L4 confirmed the increased
      amount of these proteins in the skin of cpdm/cpdm mice. Two-color
      immunofluorescence identified macrophages, dendritic cells and mast cells as
      cellular sources of Chi3L3 and Chi3L4 proteins. Eosinophils and neutrophils did
      not contain detectable concentrations of these proteins. Treatment of macrophages
      and mast cells in vitro with interleukin-4 induced expression of Chi3l3 and
      Chi3l4 mRNA.

PMID- 16984264
TI  - Are desmoglein autoantibodies essential for the immunopathogenesis of pemphigus
      vulgaris, or just "witnesses of disease"?
AB  - Pemphigus vulgaris (PV) is fascinating to dermatologists, epithelial biologists
      and immunologists alike, as its pathogenesis has been clarified to a much greater
      extent than that of most other organ-specific autoimmune diseases, and as it has
      provided abundant novel insights into desmoglein biology and pathology along the
      way. Historically, the most influential PV pathogenesis concept is that of
      Stanley and Amagai. This concept holds that autoantibodies against desmogleins
      are both essential and sufficient for epidermal blister formation (acantholysis)
      by impeding the normal functioning of these major adhesion proteins. However, as
      with most good theories, this landmark concept has left a number of intriguing
      and important questions open (or at least has not managed to answer these to
      everyone's satisfaction). Moreover, selected dissenting voices in the literature
      have increasingly called attention to what may or may not be construed as
      inconsistencies in this dominant PV pathogenesis paradigm of the recent past. The
      present debate feature therefore bravely rises to the challenge of re-examining
      the entire currently available evidence, as rationally and as undogmatically as
      possible, by provocatively asking a carefully selected congregation of experts
      (who have never before jointly published on this controversial topic!) to discuss
      how essential anti-desmoglein autoantibodies really are in the immunopathogenesis
      of PV. Not surprisingly, some of our expert "witnesses" in this animated debate
      propose diametrically opposed answers to this question. While doing so, incisive
      additional questions are raised that relate to the central one posed, and our
      attention is called to facts that may deserve more careful consideration than
      they have received so far. Together with the intriguing (often still very
      speculative) complementary or alternative pathogenesis scenarios proposed in the
      following pages, this offers welcome "food for thought" as well as very specific
      suggestions for important future research directions--within and beyond the camp
      of PV aficionados. The editors trust that this attempt at a rational public
      debate of the full evidence that is currently at hand will constructively
      contribute to further dissecting the exciting--and clinically very relevant!-
      immunopathogenesis of PV in all its complexity.

PMID- 16984277
TI  - SNPs in human beta-defensin 1 gene (DEFB1): frequencies in a Mexican population
      and new PCR-RFLPs assays.
AB  - Polymerase chain reaction-restriction fragment length polymorphism assays for two
      single nucleotide polymorphisms in the human beta-defensin 1 gene have been
      validated with real-time PCR in 101 healthy individuals from western Mexico.
      Allele frequencies were 52.5% (692-A) and 98.5% (1836-A). These assays can be
      confidently used as a cheaper alternative genotyping method for these sites.

PMID- 16984276
TI  - Investigating Gata3 as a positional candidate gene for allergic asthma in a
      murine model.
AB  - Gata3 is a positional candidate gene for allergic asthma. We determined allergen
      induced GATA-3 mRNA and protein expression in asthma susceptible and resistant
      mice and generated Gata3 sequence data. Our data indicate that the Gata3 gene in
      isolation is not a causative agent of asthma susceptibility in our model.

PMID- 16984278
TI  - A novel HLA-B allele, B*5612, identified by sequence-based typing method.
AB  - HLA-B*5612, found in Taiwan using sequence-based typing method, was identical to
      HLA-B*5502 in exon 2 but differed in exon 3 by 10 nucleotide substitutions at
      positions 353-420 leading to five amino acid change at codon 94, 95, 97, 103 and
      116. As this sequence motif was not found in the Asian population, it is likely
      that HLA-B*5612 is the product of a complex mechanism of implying a dual gene
      conversion event.

PMID- 16984279
TI  - Increase in interleukin-6 following arterial injury is related to insulin
      resistance, the -174G-->C polymorphism and complex plaque morphology.
AB  - Interleukin-6 (IL-6) is associated with many disease states in humans. We
      prospectively sought to determine whether IL-6 levels increased following
      percutaneous coronary intervention (PCI) in the absence of myonecrosis.
      Additionally, we systematically assessed other clinical and anatomic factors
      associated with IL-6 levels in a population of patients with coronary
      atherosclerosis undergoing PCI. Blood samples were collected from 117 patients at
      baseline, 8 and 16 h following PCI. Samples were assayed for IL-6, creatine
      kinase-myocardial band (CK-MB), troponin-I (Tn-I), high sensitivity C-reactive
      protein, glucose, haemoglobin A1c, and a lipid profile. Genotyping of the -174G-
      >C polymorphism of the IL-6 gene was performed. IL-6 levels increased following
      PCI among the study group (slope = 0.4 pg/mL/h, P = 0.001). IL-6 levels increased
      to a similar degree in the absence of myonecrosis. Patients with the XC genotype
      (either having the GC or the CC allele) had higher IL-6-values at baseline
      compared to GG genotype patients (4.9 +/- 6.4 vs. 2.6 +/- 1.8 pg/mL, P = 0.02).
      Multivariable predictors of detectable baseline IL-6 levels included XC genotype
      (odds ratio [OR]: 4.14, 95% CI 1.58-10.82, P = 0.004), ACC/AHA type C lesion
      classification (OR: 4.08, 95% CI 1.54-10.84, P = 0.005), elevated baseline Tn-I
      (OR: 3.31, 95% CI 1.16-9.43, P = 0.025), diabetes (OR: 3.00, 95% CI 1.11-8.09, P
      = 0.030), and waist circumference (OR: 1.49, 95% CI 1.08-2.06, P = 0.015).
      Predictors of peak IL-6 following PCI included the XC genotype (estimate 1.4, 95%
      CI 1.06-1.87, P = 0.019), homeostasis model assessment (estimate 0.99, 95% 0.982
      0.999, P = 0.042) and baseline Tn-I > upper limit of normal (estimate 0.7, 95% CI
      0.50-0.96, P = 0.039). Lastly, IL-6 increased following PCI even in the absence
      of myonecrosis as measured by Tn-I elevation. IL-6 levels are also related to the
      -174G-->C polymorphism, arterial injury, lesion complexity, and insulin
      resistance.

PMID- 16984280
TI  - Th-1 cytokines gene polymorphism in human brucellosis.
AB  - Brucellosis is a worldwide zoonosis. Infection with Brucella species results in
      the activation of cell-mediated immune response. The interaction between Th1and
      Th2 cytokines determines the outcome of disease. Production of each cytokine is
      in turn affected by genetic factors. In this study, we investigated the possible
      association between Th1 cytokines gene polymorphism and brucellosis. Different
      genotypes of TNF-alpha, IFN-gamma and IL-2 were determined by polymerase chain
      reaction-sequence-specific primer in 47 patients with brucellosis and in 166
      healthy controls. Allele frequencies of these genotypes were compared using the
      chi2 test. The results showed a significant difference in the TNF-alpha genotype
      GG/GG in patients in comparison with controls (76.7% vs. 21%) (P = 0.001, OR =
      12.42, 95%CI 5.7-27.7). There was no significant difference in the frequency
      distribution of the IFN-gamma genotypes between two groups. IL-2 GG genotype at
      position -330 was about two times more common in cases than in controls, but the
      difference was not significant (10.6 vs. 4.6 P value = 0.09). This study shows
      that genetically low producers of TNF-alpha are possibly susceptible to
      brucellosis and raise doubt about the role of gene polymorphism of INF-gamma in
      brucellosis which was demonstrated in previous studies. It seems that patients
      with brucellosis did not have a defect in producing IL-2 with even a trend
      towards producing higher amounts of this cytokine.

PMID- 16984282
TI  - A novel HLA-B*2730 allele found in a Slovene patient affected with IgA
      nephropathy.
AB  - A novel allele HLA-B*2730 and the haplotype HLA-A*03-B*2730-Cw*02-DRB1*16-DRB5
      have been found in a Slovene patient and his mother. The exon 2 sequence is
      identical to that of HLA-B*2702, and the exon 3 sequence is identical to that of
      HLA-B*2719. A possible mechanism for the generation of B*2730 is a gene
      conversion event.

PMID- 16984281
TI  - Identification of variations in the human phosphoinositide 3-kinase p110delta
      gene in children with primary B-cell immunodeficiency of unknown aetiology.
AB  - Our recent study demonstrated that defects in p110delta result in B-cell
      immunodeficiency that is very similar to that observed in BTK-deficient mice. We
      revealed that the p110delta fit the B-cell signal transduction complex and played
      a non-redundant role in the development and function of B cells. In humans, most
      children with primary B-cell immunodeficiency have mutations in the BTK, whereas
      a few have defects in the components of the B-cell signal transduction complex.
      But little is known about the genetic variation of p110delta in children with
      defects in B-cell immunodeficiency of unknown aetiology. Sixteen patients from 15
      unrelated families and 112 normal controls underwent sequence analysis to
      identify genetic variations of the p110delta. Allele frequency in each group was
      also analysed and compared. We identified five single base-pair polymorphic
      nucleotide exchanges in both patient and control groups with similar allele
      frequencies, which did not contribute to the immunodeficiency. Three of them are
      novel (m.953A>G, m.1200C>T and m.1561A>G), and the m.953A>G and m.1561A>G
      nucleotide exchanges are non-synonymous (N253S and T456A, respectively). The
      novel m.1561A>G was in complete linkage disequilibrium with the known m.873A>G in
      our study of Taiwanese group. In addition, one novel single base-pair missense
      mutation, m.3256G>A (E1021K), was identified in one boy with typical clinical
      features of primary B-cell immunodeficiency and could not be found in either his
      family or the normal control population. By atomic structural analysis of the
      amino acid as well as the alignment comparison between species, it resulted in
      the replacement of the negative-charged amino acid E with the positive-charged
      amino acid K at codon 1021, located in the highly conservative and important
      catalytic functional domain. Our findings could shed light on further
      understanding the polymorphisms of p110delta in B-cell immunodeficiency and
      different populations. Moreover, the 3256G>A missense mutation raised the
      attention and warranted further extensive analysis to elucidate the role of
      p110delta in human immunodeficiency.

PMID- 16984283
TI  - Role of non-HLA genetic polymorphisms in graft-versus-host disease after
      haematopoietic stem cell transplantation.
AB  - Graft-versus-host disease (GvHD) is the main complication after haematopoietic
      stem cells transplantation (HSCT) and acute forms (aGvHD) occur in 20-40% of
      cases even after donor (D) and recipient (R) HLA matching, apparently because of
      D/R minor histocompatibility antigen (mHA) mismatches and cytokine polymorphisms.
      The genotype of cytokines and mHA of 77 haematological R following HSCT from HLA
      identical siblings were determined to detect genetic polymorphisms correlated
      with GvHD. We analysed TNFA (-863 C/A, -857 C/T and G/A at positions -574, -376, 
      308, -244, -238), IL-10 (-1082 G/A, -819 C/A, -592 C/T), IL-1B (T/C +3953), IL
      1RA (VNTR), HA-1 (H/R allele) and CD-31 (C/G at codon 125, A/G at codon 563).
      Allele frequencies were in Hardy-Weinberg equilibrium and similar to those of 77
      healthy controls. We observed positive correlations between a lower risk of
      clinically significant aGvHD and both the presence of -1082G -819C -592C IL-10
      haplotype when both R and D are considered together and the absence of R IL-1RA
      allele 2. Furthermore, we observed an association between the absence of TNF-A 
      238 A allele and the risk of extensive chronic GvHD. mHA and cytokines genotyping
      would thus seem a valid source of information for the prior identification of
      recipients with a higher risk of aGvHD.

PMID- 16984287
TI  - Language and action control: the acquisition of action goals in early childhood.
AB  - This study examined the role of verbal labeling in 4-year-old children's
      acquisition of action-effect learning. The acquisition of action-effect
      associations was tested by having children first perform a two-choice key
      pressing task in which each key press was followed by an effect (i.e., a
      particular sound) and then respond to the previously perceived effects under
      either consistent or inconsistent key-sound mappings. During acquisition, the
      children overtly described the actions, the effects, both the actions and the
      effects, or, in a control condition, something irrelevant to the actions and
      effects. Action-effect learning was reliable only if the description related
      actions to effects, even though some evidence of learning was also obtained in
      the control condition. In contrast, learning was prevented if only the actions or
      only the effects were described. The results suggest that verbal labeling plays
      an important role in integrating and isolating event representations.

PMID- 16984288
TI  - Examining the word identification stages hypothesized by the E-Z Reader model.
AB  - A critical prediction of the E-Z Reader model is that experimental manipulations
      that disrupt early encoding of visual and orthographic features of the fixated
      word without affecting subsequent lexical processing should influence the
      processing difficulty of the fixated word without affecting the processing of the
      next word. We tested this prediction by monitoring participants' eye movements
      while they read sentences in which a target word was presented either normally or
      altered. In the critical condition, the contrast between the target word and the
      background was substantially reduced. Such a reduction in stimulus quality is
      typically assumed to have an impact that is largely confined to a very early
      stage of word recognition. Results were consistent with the E-Z Reader model:
      This faint presentation had a robust influence on the duration of fixations on
      the target word without substantially altering the processing of the next word.

PMID- 16984289
TI  - Tactful or doubtful? Expectations of politeness explain the severity bias in the
      interpretation of probability phrases.
AB  - When a statement about the occurrence of a medical condition is qualified by an
      expression of probability, such as the word possible, listeners interpret the
      probability of the condition as being higher the more severe the condition. This
      severity bias can have serious consequences for the well-being of patients. We
      argue that the bias is due to a misconception of the pragmatic function served by
      the expression of probability. The more severe the condition, the greater the
      chance that the listener construes the expression as a politeness marker rather
      than as an uncertainty marker. When this misconception does not occur, neither
      should the severity bias. An analysis of interpretations of probability
      expressions using a membership-function approach validates this account. We
      discuss the consequences of this bias for the communication of risk within and
      outside the medical domain.

PMID- 16984290
TI  - Attention speeds binocular rivalry.
AB  - During binocular rivalry, incompatible images presented dichoptically compete for
      perceptual dominance. It has long been debated whether binocular rivalry can be
      controlled by attention. Most studies have shown that voluntary control over
      binocular rivalry is limited. We sought to remove attention from binocular
      rivalry by presenting a concurrent task. Diverting attention slowed the rivalry
      alternation rate, and did so in proportion to the difficulty of the concurrent
      task. Even a very demanding distractor task, however, did not arrest rivalry
      alternations completely. Given that diverting attention was equivalent to
      lowering the contrast of the rival stimuli, the ability of attention to speed
      binocular rivalry is most likely due to an increase in the effective contrast of
      the stimuli through boosting the gain of the cortical response. This increase in
      effective contrast will ultimately lead to a perceptual switch, thereby limiting
      voluntary control. Thus, attention speeds rivalry alternations, but has no
      inherent control over the rivalry process.

PMID- 16984291
TI  - Adults don't always know best: preschoolers use past reliability over age when
      learning new words.

PMID- 16984292
TI  - Beliefs about essences and the reality of mental disorders.
AB  - Do people believe mental disorders are real and possess underlying essences? The
      current study found that both novices and practicing clinicians held weaker
      essentialist beliefs about mental disorders than about medical disorders. They
      were also unwilling to endorse the idea that mental disorders are real and
      natural. Furthermore, compared with novices, mental health clinicians were less
      likely to endorse the view that there is a shared cause underlying a mental
      disorder and that one needs to remove the cause to get rid of the mental
      disorder. Clinicians were polarized on their views about whether mental disorders
      are categorical or dimensional. These findings reflect current controversies
      about mental disorders in the field at large.

PMID- 16984293
TI  - Optimal predictions in everyday cognition.
AB  - Human perception and memory are often explained as optimal statistical inferences
      that are informed by accurate prior probabilities. In contrast, cognitive
      judgments are usually viewed as following error-prone heuristics that are
      insensitive to priors. We examined the optimality of human cognition in a more
      realistic context than typical laboratory studies, asking people to make
      predictions about the duration or extent of everyday phenomena such as human life
      spans and the box-office take of movies. Our results suggest that everyday
      cognitive judgments follow the same optimal statistical principles as perception
      and memory, and reveal a close correspondence between people's implicit
      probabilistic models and the statistics of the world.

PMID- 16984294
TI  - On how to be unpredictable: evidence from the voluntary task-switching paradigm.
AB  - The voluntary task-switching paradigm requires subjects to select randomly
      between tasks and promises to provide a window into executive task selection
      independent of exogenous influences present in standard task-switching
      situations. We show here that the degree to which subjects perseverate on tasks
      across trials captures unique individual differences variance, but also that the
      switch rate is under strong stimulus-driven control: "Voluntary" switches are
      much more frequent when the stimulus changes than when it repeats. Most
      important, we show that individuals whose no-switch trials are selectively slowed
      exhibit less perseveration and stimulus-driven effects (and thus more voluntary
      selection) than individuals whose no-switch trials do not show this slowing. We
      suggest that selective slowing indicates a strategy of treating trials as
      discrete events--possibly through inhibition of the preceding task set. These
      results not only demonstrate massive nonvoluntary influences on voluntary
      selection that are largely untapped by standard task-switching measures, but also
      show how such influences can be counteracted through strategic adaptations.

PMID- 16984295
TI  - Rapid development of feature binding in visual short-term memory.
AB  - The binding of object identity (color) and location in visual short-term memory
      (VSTM) was examined in 6.5- to 12.5-month-old infants (N= 144). Although we
      previously found that by age 6.5 months, infants can represent both color and
      location in VSTM, in the present study we observed that 6.5-month-old infants
      could not remember trivially simple color-location combinations across a 300-ms
      delay. However, 7.5-month-old infants could bind color and location as
      effectively as 12.5-month-old infants. Control conditions confirmed that the
      failure of 6.5-month-old infants was not a result of perceptual or attentional
      limitations. This rapid development of VSTM binding between 6.5 and 7.5 months
      occurs during a period of rapid increase in VSTM storage capacity and just after
      a period of dramatic neuroanatomical changes in parietal cortex. Thus, the
      ability to bind features and the ability to store multiple objects may both
      depend on a process that is mediated by posterior parietal cortex and is perhaps
      related to focused attention.

PMID- 16984296
TI  - Motor limitation in dual-task processing under ballistic movement conditions.
AB  - The standard bottleneck model of the psychological refractory period (PRP)
      assumes that the selection of the second response is postponed until the first
      response has been selected. Accordingly, dual-task interference is attributed to
      a single central-processing bottleneck involving decision and response selection,
      but not the execution of the response itself. In order to critically examine the
      assumption that response execution is not part of this bottleneck, we
      systematically manipulated the temporal demand for executing the first response
      in a classical PRP paradigm. Contrary to the assumption of the standard
      bottleneck model, this manipulation affected the reaction time for Task 2.
      Specifically, reaction time for Task 2 increased with execution time for Task 1.
      This carryover effect from Task 1 to Task 2 provides evidence for the notion that
      response execution can be part of the processing bottleneck.

PMID- 16984297
TI  - Moving farther but faster: an exception to Fitts's law.
AB  - Fitts's law holds that movement time (MT) increases with longer distances. Here
      we report a violation of this law: When the target appears in a structured,
      linear display with placeholders indicating the possible target locations, MT to
      the most distant target is not longer than MT to the second most distant target,
      but rather tends to be shorter. Furthermore, the presence of placeholders
      attenuates the range effect that occurs in the absence of placeholders. These
      findings suggest that Fitts's law may be limited to egocentric visuomotor action,
      and that the visual control of hand movements may use allocentric, in addition to
      egocentric, spatial information.

PMID- 16984298
TI  - Prototypes are attractive because they are easy on the mind.
AB  - People tend to prefer highly prototypical stimuli--a phenomenon referred to as
      the beauty-in-averageness effect. A common explanation of this effect proposes
      that prototypicality signals mate value. Here we present three experiments
      testing whether prototypicality preference results from more general mechanisms
      fluent processing of prototypes and preference for fluently processed stimuli. In
      two experiments, participants categorized and rated the attractiveness of random
      dot patterns (Experiment 1) or common geometric patterns (Experiment 2) that
      varied in levels of prototypicality. In both experiments, prototypicality was a
      predictor of both fluency (categorization speed) and attractiveness. Critically,
      fluency mediated the effect of prototypicality on attractiveness, although some
      effect of prototypicality remained when fluency was controlled. The findings were
      the same whether or not participants explicitly considered the pattern's
      categorical membership, and whether or not categorization fluency was salient
      when they rated attractiveness. Experiment 3, using the psychophysiological
      technique of facial electromyography, confirmed that viewing abstract prototypes
      elicits quick positive affective reactions.

PMID- 16984299
TI  - Manic thinking: independent effects of thought speed and thought content on mood.
AB  - This experiment found that the speed of thought affects mood. Thought speed was
      manipulated via participants' paced reading of statements designed to induce
      either an elated or a depressed mood. Participants not only experienced more
      positive mood in response to elation than in response to depression statements,
      but also experienced an independent increase in positive mood when they had been
      thinking fast rather than slow--for both elation and depression statements. This
      effect of thought speed extended beyond mood to other experiences often
      associated with mania (i.e., feelings of power, feelings of creativity, a
      heightened sense of energy, and inflated self-esteem or grandiosity).

PMID- 16984300
TI  - Contextual diversity, not word frequency, determines word-naming and lexical
      decision times.
AB  - Word frequency is an important predictor of word-naming and lexical decision
      times. It is, however, confounded with contextual diversity, the number of
      contexts in which a word has been seen. In a study using a normative, corpus
      based measure of contextual diversity, word-frequency effects were eliminated
      when effects of contextual diversity were taken into account (but not vice versa)
      across three naming and three lexical decision data sets; the same pattern of
      results was obtained regardless of which of three corpora was used to derive the
      frequency and contextual-diversity values. The results are incompatible with
      existing models of visual word recognition, which attribute frequency effects
      directly to frequency, and are particularly problematic for accounts in which
      frequency effects reflect learning. We argue that the results reflect the
      importance of likely need in memory processes, and that the continuity between
      reading and memory suggests using principles from memory research to inform
      theories of reading.

PMID- 16984301
TI  - Computational biology: toward deciphering gene regulatory information in
      mammalian genomes.
AB  - Computational biology is a rapidly evolving area where methodologies from
      computer science, mathematics, and statistics are applied to address fundamental
      problems in biology. The study of gene regulatory information is a central
      problem in current computational biology. This article reviews recent development
      of statistical methods related to this field. Starting from microarray gene
      selection, we examine methods for finding transcription factor binding motifs and
      cis-regulatory modules in coregulated genes, and methods for utilizing
      information from cross-species comparisons and ChIP-chip experiments. The
      ultimate understanding of cis-regulatory logic in mammalian genomes may require
      the integration of information collected from all these steps.

PMID- 16984302
TI  - Are flexible designs sound?
AB  - Flexible designs allow large modifications of a design during an experiment. In
      particular, the sample size can be modified in response to interim data or
      external information. A standard flexible methodology combines such design
      modifications with a weighted test, which guarantees the type I error level.
      However, this inference violates basic inference principles. In an example with
      independent N(mu, 1) observations, the test rejects the null hypothesis of mu <
      or = 0 while the average of the observations is negative. We conclude that
      flexible design in its most general form with the corresponding weighted test is
      not valid. Several possible modifications of the flexible design methodology are
      discussed with a focus on alternative hypothesis tests.

PMID- 16984308
TI  - Semiparametric estimation of animal abundance using capture-recapture data from
      open populations.
AB  - A semiparametric partially linear model for the size of an open population is
      proposed and inference is conducted using weighted martingale estimating
      equations. This extends a previous nonparametric approach to modeling capture
      recapture data for open populations with frequent capture occasions. Analytic
      expressions for the large sample variances are derived and these are confirmed in
      a simulation study. The method is illustrated on monthly penguin banding data
      collected over 6 years.

PMID- 16984309
TI  - Semiparametric regression in capture-recapture modeling.
AB  - Capture-recapture models were developed to estimate survival using data arising
      from marking and monitoring wild animals over time. Variation in survival may be
      explained by incorporating relevant covariates. We propose nonparametric and
      semiparametric regression methods for estimating survival in capture-recapture
      models. A fully Bayesian approach using Markov chain Monte Carlo simulations was
      employed to estimate the model parameters. The work is illustrated by a study of
      Snow petrels, in which survival probabilities are expressed as nonlinear
      functions of a climate covariate, using data from a 40-year study on marked
      individuals, nesting at Petrels Island, Terre Adelie.

PMID- 16984310
TI  - The Jolly-Seber model with tag loss.
AB  - Tag loss in mark-recapture experiments is a violation of one of the Jolly-Seber
      model assumptions. It causes bias in parameter estimates and has only been dealt
      with in an ad hoc manner. We develop methodology to estimate tag retention and
      abundance in double-tagging mark-recapture experiments. We apply this methodology
      to walleyes (Stizostedion vitreum) in Mille Lacs, Minnesota.

PMID- 16984311
TI  - Bayesian estimation of species richness from quadrat sampling data in the
      presence of prior information.
AB  - We consider the problem of estimating the number of species of an animal
      community. It is assumed that it is possible to draw up a list of species liable
      to be present in this community. Data are collected from quadrat sampling. Models
      considered in this article separate the assumptions related to the experimental
      protocol and those related to the spatial distribution of species in the
      quadrats. Our parameterization enables us to incorporate prior information on the
      presence, detectability, and spatial density of species. Moreover, we elaborate
      procedures to build the prior distributions on these parameters from information
      furnished by external data. A simulation study is carried out to examine the
      influence of different priors on the performances of our estimator. We illustrate
      our approach by estimating the number of nesting bird species in a forest.

PMID- 16984312
TI  - Local influence diagnostics for quasi-likelihood and lognormal estimates of a
      biological reference point from some fish stock and recruitment models.
AB  - We present local influence diagnostics to measure the sensitivity of a biological
      limit reference point (LRP) estimated from fitting a model to stock and
      recruitment data. LRPs are low levels of stock size that the management of
      commercial fisheries should avoid with high probability. The LRP we examine is
      the stock size at which recruitment is 50% of the maximum (S(50%)). We derive
      analytic equations to describe the effects on S(50%) of changing the weight that
      observations are given in estimation. We derive equations for the Ricker,
      Beverton-Holt, and hockey-stick stock-recruit models, and four estimation methods
      including the error sums of squares method on log responses and three quasi
      likelihood methods. We conclude from case studies that the hockey-stick model
      produces the most robust estimates.

PMID- 16984313
TI  - A statistical test of the hypothesis that polyclonal intestinal tumors arise by
      random collision of initiated clones.
AB  - The random collision hypothesis is a mathematical idealization of intestinal
      tumor formation that can account for the polyclonal origin of tumors without
      requiring a mechanistic description of clonal interaction. Using data from recent
      polyclonality studies in mice, we develop a statistical procedure to test the
      random collision hypothesis. Elements from stochastic geometry and approximations
      due to Armitage (1949, Biometrika 36, 257-266) support a statistical model of
      tumor count data. Bayesian analysis yields the posterior distribution of the
      number of heterotypic tumors, from which p-values are computed to test random
      collision.

PMID- 16984314
TI  - Improving estimates of genetic maps: a maximum likelihood approach.
AB  - As a result of previous large, multipoint linkage studies there is a substantial
      amount of existing marker data. Due to the increased sample size, genetic maps
      estimated from these data could be more accurate than publicly available maps.
      However, current methods for map estimation are restricted to data sets
      containing pedigrees with a small number of individuals, or cannot make full use
      of marker data that are observed at several loci on members of large, extended
      pedigrees. In this article, a maximum likelihood (ML) method for map estimation
      that can make full use of the marker data in a large, multipoint linkage study is
      described. The method is applied to replicate sets of simulated marker data
      involving seven linked loci, and pedigree structures based on the real multipoint
      linkage study of Abkevich et al. (2003, American Journal of Human Genetics 73,
      1271-1281). The variance of the ML estimate is accurately estimated, and tests of
      both simple and composite null hypotheses are performed. An efficient procedure
      for combining map estimates over data sets is also suggested.

PMID- 16984315
TI  - Parametric and nonparametric FDR estimation revisited.
AB  - Nonparametric and parametric approaches have been proposed to estimate false
      discovery rate under the independent hypothesis testing assumption. The
      parametric approach has been shown to have better performance than the
      nonparametric approaches. In this article, we study the nonparametric approaches
      and quantify the underlying relations between parametric and nonparametric
      approaches. Our study reveals the conservative nature of the nonparametric
      approaches, and establishes the connections between the empirical Bayes method
      and p-value-based nonparametric methods. Based on our results, we advocate using
      the parametric approach, or directly modeling the test statistics using the
      empirical Bayes method.

PMID- 16984316
TI  - Using bivariate models to understand between- and within-cluster regression
      coefficients, with application to twin data.
AB  - In the regression analysis of clustered data it is important to allow for the
      possibility of distinct between- and within-cluster exposure effects on the
      outcome measure, represented, respectively, by regression coefficients for the
      cluster mean and the deviation of the individual-level exposure value from this
      mean. In twin data, the within-pair regression effect represents association
      conditional on exposures shared within pairs, including any common genetic or
      environmental influences on the outcome measure. It has therefore been proposed
      that a comparison of the within-pair regression effects between monozygous (MZ)
      and dizygous (DZ) twins can be used to examine whether the association between
      exposure and outcome has a genetic origin. We address this issue by proposing a
      bivariate model for exposure and outcome measurements in twin-pair data. The
      between- and within-pair regression coefficients are shown to be weighted
      averages of ratios of the exposure and outcome variances and covariances, from
      which it is straightforward to determine the conditions under which the within
      pair regression effect in MZ pairs will be different from that in DZ pairs. In
      particular, we show that a correlation structure in twin pairs for exposure and
      outcome that appears to be due to genetic factors will not necessarily be
      reflected in distinct MZ and DZ values for the within-pair regression
      coefficients. We illustrate these results in a study of female twin pairs from
      Australia and North America relating mammographic breast density to weight and
      body mass index.

PMID- 16984317
TI  - A general approach for two-stage analysis of multilevel clustered non-Gaussian
      data.
AB  - In this article, we propose a two-stage approach to modeling multilevel clustered
      non-Gaussian data with sufficiently large numbers of continuous measures per
      cluster. Such data are common in biological and medical studies utilizing
      monitoring or image-processing equipment. We consider a general class of
      hierarchical models that generalizes the model in the global two-stage (GTS)
      method for nonlinear mixed effects models by using any square-root-n-consistent
      and asymptotically normal estimators from stage 1 as pseudodata in the stage 2
      model, and by extending the stage 2 model to accommodate random effects from
      multiple levels of clustering. The second-stage model is a standard linear mixed
      effects model with normal random effects, but the cluster-specific distributions,
      conditional on random effects, can be non-Gaussian. This methodology provides a
      flexible framework for modeling not only a location parameter but also other
      characteristics of conditional distributions that may be of specific interest.
      For estimation of the population parameters, we propose a conditional restricted
      maximum likelihood (CREML) approach and establish the asymptotic properties of
      the CREML estimators. The proposed general approach is illustrated using
      quartiles as cluster-specific parameters estimated in the first stage, and
      applied to the data example from a collagen fibril development study. We
      demonstrate using simulations that in samples with small numbers of independent
      clusters, the CREML estimators may perform better than conditional maximum
      likelihood estimators, which are a direct extension of the estimators from the
      GTS method.

PMID- 16984318
TI  - The performance of random coefficient regression in accounting for residual
      confounding.
AB  - Greenland (2000, Biometrics 56, 915-921) describes the use of random coefficient
      regression to adjust for residual confounding in a particular setting. We examine
      this setting further, giving theoretical and empirical results concerning the
      frequentist and Bayesian performance of random coefficient regression.
      Particularly, we compare estimators based on this adjustment for residual
      confounding to estimators based on the assumption of no residual confounding.
      This devolves to comparing an estimator from a nonidentified but more realistic
      model to an estimator from a less realistic but identified model. The approach
      described by Gustafson (2005, Statistical Science 20, 111-140) is used to
      quantify the performance of a Bayesian estimator arising from a nonidentified
      model. From both theoretical calculations and simulations we find support for the
      idea that superior performance can be obtained by replacing unrealistic
      identifying constraints with priors that allow modest departures from those
      constraints. In terms of point-estimator bias this superiority arises when the
      extent of residual confounding is substantial, but the advantage is much broader
      in terms of interval estimation. The benefit from modeling residual confounding
      is maintained when the prior distributions employed only roughly correspond to
      reality, for the standard identifying constraints are equivalent to priors that
      typically correspond much worse.

PMID- 16984319
TI  - Case-only analysis of treatment-covariate interactions in clinical trials.
AB  - Differential effectiveness of treatments across subgroups defined by pretreatment
      variables are of increasing interest, particularly in the expanding research
      field of pharmacogenomics. When the pretreatment variable is difficult to obtain
      or expensive to measure, but can be assessed at the end of the study using stored
      samples, nested case-control and case-cohort methods can be used to reduce costs
      in large efficacy trials with rare outcomes. Case-only methods are even more
      efficient, and reliable under a range of circumstances.

PMID- 16984320
TI  - Bayesian dose-finding in phase I/II clinical trials using toxicity and efficacy
      odds ratios.
AB  - A Bayesian adaptive design is proposed for dose-finding in phase I/II clinical
      trials to incorporate the bivariate outcomes, toxicity and efficacy, of a new
      treatment. Without specifying any parametric functional form for the drug dose
      response curve, we jointly model the bivariate binary data to account for the
      correlation between toxicity and efficacy. After observing all the responses of
      each cohort of patients, the dosage for the next cohort is escalated,
      deescalated, or unchanged according to the proposed odds ratio criteria
      constructed from the posterior toxicity and efficacy probabilities. A novel class
      of prior distributions is proposed through logit transformations which implicitly
      imposes a monotonic constraint on dose toxicity probabilities and correlates the
      probabilities of the bivariate outcomes. We conduct simulation studies to
      evaluate the operating characteristics of the proposed method. Under various
      scenarios, the new Bayesian design based on the toxicity-efficacy odds ratio
      trade-offs exhibits good properties and treats most patients at the desirable
      dose levels. The method is illustrated with a real trial design for a breast
      medical oncology study.

PMID- 16984321
TI  - Using journal impact factors to correct for the publication bias of medical
      studies.
AB  - Publication bias of the results of medical studies can invalidate evidence-based
      medicine. The existing methodology for modeling this essentially relies upon the
      symmetry of the funnel plot. We present a new method of modeling publication bias
      that uses this information plus the impact factors of the publishing journals. A
      simple model of the publication process enables the estimation of bias-corrected
      intervention effects. The procedure is illustrated using a meta-analysis of the
      effectiveness of single-dose oral aspirin for acute pain, and results are also
      obtained for five other meta-analyses. The method enables the fitting of a wide
      range of models and is considered more flexible than other ways of compensating
      for publication bias. The model also provides the basis of a statistical test for
      the existence of publication bias. Use of the new methodology to supplement
      existing methods is recommended, in the context of a sensitivity analysis.

PMID- 16984322
TI  - Polynomial spline estimation and inference of proportional hazards regression
      models with flexible relative risk form.
AB  - The Cox proportional hazards model usually assumes an exponential form for the
      dependence of the hazard function on covariate variables. However, in practice
      this assumption may be violated and other relative risk forms may be more
      appropriate. In this article, we consider the proportional hazards model with an
      unknown relative risk form. Issues in model interpretation are addressed. We
      propose a method to estimate the relative risk form and the regression parameters
      simultaneously by first approximating the logarithm of the relative risk form by
      a spline, and then employing the maximum partial likelihood estimation. An
      iterative alternating optimization procedure is developed for efficient
      implementation. Statistical inference of the regression coefficients and of the
      relative risk form based on parametric asymptotic theory is discussed. The
      proposed methods are illustrated using simulation and an application to the
      Veteran's Administration lung cancer data.

PMID- 16984323
TI  - Smoothing spline-based score tests for proportional hazards models.
AB  - We propose "score-type" tests for the proportional hazards assumption and for
      covariate effects in the Cox model using the natural smoothing spline
      representation of the corresponding nonparametric functions of time or covariate.
      The tests are based on the penalized partial likelihood and are derived by
      viewing the inverse of the smoothing parameter as a variance component and
      testing an equivalent null hypothesis that the variance component is zero. We
      show that the tests have a size close to the nominal level and good power against
      general alternatives, and we apply them to data from a cancer clinical trial.

PMID- 16984324
TI  - Regularized estimation in the accelerated failure time model with high
      dimensional covariates.
AB  - We consider two regularization approaches, the LASSO and the threshold-gradient
      directed regularization, for estimation and variable selection in the accelerated
      failure time model with multiple covariates based on Stute's weighted least
      squares method. The Stute estimator uses Kaplan-Meier weights to account for
      censoring in the least squares criterion. The weighted least squares objective
      function makes the adaptation of this approach to multiple covariate settings
      computationally feasible. We use V-fold cross-validation and a modified Akaike's
      Information Criterion for tuning parameter selection, and a bootstrap approach
      for variance estimation. The proposed method is evaluated using simulations and
      demonstrated on a real data example.

PMID- 16984325
TI  - Analysis of a partially observed binary covariate process and a censored failure
      time in the presence of truncation and competing risks.
AB  - We develop methods for assessing the association between a binary time-dependent
      covariate process and a failure time endpoint when the former is observed only at
      a single time point and the latter is right censored, and when the observations
      are subject to truncation and competing causes of failure. Using a proportional
      hazards model for the effect of the covariate process on the failure time of
      interest, we develop an approach utilizing EM algorithm and profile likelihood
      for estimating the relative risk parameter and cause-specific hazards for
      failure. The methods are extended to account for other covariates that can
      influence the time-dependent covariate process and cause-specific risks of
      failure. We illustrate the methods with data from a recent study on the
      association between loss of hepatitis B e antigen and the development of
      hepatocellular carcinoma in a population of chronic carriers of hepatitis B.

PMID- 16984326
TI  - Nonparametric estimation of stage occupation probabilities in a multistage model
      with current status data.
AB  - Multistage models are used to describe individuals (or experimental units) moving
      through a succession of "stages" corresponding to distinct states (e.g., healthy,
      diseased, diseased with complications, dead). The resulting data can be
      considered to be a form of multivariate survival data containing information
      about the transition times and the stages occupied. Traditional survival analysis
      is the simplest example of a multistage model, where individuals begin in an
      initial stage (say, alive) and move irreversibly to a second stage (death). In
      this article, we consider general multistage models with a directed tree
      structure (progressive models) in which individuals traverse through stages in a
      possibly non-Markovian manner. We construct nonparametric estimators of stage
      occupation probabilities and marginal cumulative transition hazards. Empirical
      calculations of these quantities are not possible due to the lack of complete
      data. We consider current status information which represents a more severe form
      of censoring than the commonly used right censoring. Asymptotic validity of our
      estimators can be justified using consistency results for nonparametric
      regression estimators. Finite-sample behavior of our estimators is studied by
      simulation, in which we show that our estimators based on these limited data
      compare well with those based on complete data. We also apply our method to a
      real-life data set arising from a cardiovascular diseases study in Taiwan.

PMID- 16984327
TI  - Estimating the distribution of a renewal process from times at which events from
      an independent process are detected.
AB  - The analysis of length-biased data has been mostly limited to the interarrival
      interval of a renewal process covering a specific time point. Motivated by a
      surveillance problem, we consider a more general situation where this time point
      is random and related to a specific event, for example, status change or onset of
      a disease. We also consider the problem when additional information is available
      on whether the event intervals (interarrival intervals covering the random event)
      end within or after a random time period (which we call a window period)
      following the random event. Under the assumptions that the occurrence rate of the
      random event is low and the renewal process is independent of the random event,
      we provide formulae for the estimation of the distribution of interarrival times
      based on the observed event intervals. Procedures for testing the required
      assumptions are also furnished. We apply our results to human immunodeficiency
      virus (HIV) test data from public test sites in Seattle, Washington, where the
      random event is HIV infection and the window period is from the onset of HIV
      infection to the time at which a less sensitive HIV test becomes positive.
      Results show that the estimator of the intertest interval length distribution
      from event intervals ending within the window period is less biased than the
      estimator from all event intervals; the latter estimator is affected by right
      truncation. Finally, we discuss possible applications to estimating HIV incidence
      and analyzing length-biased samples with right or left truncated data.

PMID- 16984328
TI  - Estimating average annual percent change for disease rates without assuming
      constant change.
AB  - The annual percent change (APC) is often used to measure trends in disease and
      mortality rates, and a common estimator of this parameter uses a linear model on
      the log of the age-standardized rates. Under the assumption of linearity on the
      log scale, which is equivalent to a constant change assumption, APC can be
      equivalently defined in three ways as transformations of either (1) the slope of
      the line that runs through the log of each rate, (2) the ratio of the last rate
      to the first rate in the series, or (3) the geometric mean of the proportional
      changes in the rates over the series. When the constant change assumption fails
      then the first definition cannot be applied as is, while the second and third
      definitions unambiguously define the same parameter regardless of whether the
      assumption holds. We call this parameter the percent change annualized (PCA) and
      propose two new estimators of it. The first, the two-point estimator, uses only
      the first and last rates, assuming nothing about the rates in between. This
      estimator requires fewer assumptions and is asymptotically unbiased as the size
      of the population gets large, but has more variability since it uses no
      information from the middle rates. The second estimator is an adaptive one and
      equals the linear model estimator with a high probability when the rates are not
      significantly different from linear on the log scale, but includes fewer points
      if there are significant departures from that linearity. For the two-point
      estimator we can use confidence intervals previously developed for ratios of
      directly standardized rates. For the adaptive estimator, we show through
      simulation that the bootstrap confidence intervals give appropriate coverage.

PMID- 16984329
TI  - Spatial association between speciated fine particles and mortality.
AB  - Particulate matter (PM) has been linked to a range of serious cardiovascular and
      respiratory health problems, including premature mortality. The main objective of
      our research is to quantify uncertainties about the impacts of fine PM exposure
      on mortality. We develop a multivariate spatial regression model for the
      estimation of the risk of mortality associated with fine PM and its components
      across all counties in the conterminous United States. We characterize different
      sources of uncertainty in the data and model the spatial structure of the
      mortality data and the speciated fine PM. We consider a flexible Bayesian
      hierarchical model for a space-time series of counts (mortality) by constructing
      a likelihood-based version of a generalized Poisson regression model that
      combines methods for point-level misaligned data and change of support
      regression. Our results seem to suggest an increase by a factor of two in the
      risk of mortality due to fine particles with respect to coarse particles. Our
      study also shows that in the Western United States, the nitrate and crustal
      components of the speciated fine PM seem to have more impact on mortality than
      the other components. On the other hand, in the Eastern United States, sulfate
      and ammonium explain most of the fine PM effect.

PMID- 16984330
TI  - Coregionalized single- and multiresolution spatially varying growth curve
      modeling with application to weed growth.
AB  - Modeling of longitudinal data from agricultural experiments using growth curves
      helps understand conditions conducive or unconducive to crop growth. Recent
      advances in Geographical Information Systems (GIS) now allow geocoding of
      agricultural data that help understand spatial patterns. A particularly common
      problem is capturing spatial variation in growth patterns over the entire
      experimental domain. Statistical modeling in these settings can be challenging
      because agricultural designs are often spatially replicated, with arrays of
      subplots, and interest lies in capturing spatial variation at possibly different
      resolutions. In this article, we develop a framework for modeling spatially
      varying growth curves as Gaussian processes that capture associations at single
      and multiple resolutions. We provide Bayesian hierarchical models for this
      setting, where flexible parameterization enables spatial estimation and
      prediction of growth curves. We illustrate using data from weed growth
      experiments conducted in Waseca, Minnesota, that recorded growth of the weed
      Setaria spp. in a spatially replicated design.

PMID- 16984331
TI  - A multivariate two-sample mean test for small sample size and missing data.
AB  - We develop a new statistic for testing the equality of two multivariate mean
      vectors. A scaled chi-squared distribution is proposed as an approximating null
      distribution. Because the test statistic is based on componentwise statistics, it
      has the advantage over Hotelling's T2 test of being applicable to the case where
      the dimension of an observation exceeds the number of observations. An appealing
      feature of the new test is its ability to handle missing data by relying on only
      componentwise sample moments. Monte Carlo studies indicate good power compared to
      Hotelling's T2 and a recently proposed test by Srivastava (2004, Technical
      Report, University of Toronto). The test is applied to drug discovery data.

PMID- 16984332
TI  - Optimal experimental design for a nonlinear response in environmental toxicology.
AB  - A start-stop experiment in environmental toxicology provides a backdrop for this
      design discussion. The basic problem is to decide when to sample a nonlinear
      response in order to minimize the generalized variance of the estimated
      parameters. An easily coded heuristic optimization strategy can be applied to
      this problem to obtain optimal or nearly optimal designs. The efficiency of the
      heuristic approach allows a straightforward exploration of the sensitivity of the
      suggested design with respect to such problem-specific concerns as variance
      heterogeneity, time-grid resolution, design criteria, and interval specification
      of planning values for parameters. A second illustration of design optimization
      is briefly presented in the context of concentration spacing for a reproductive
      toxicity study.

PMID- 16984333
TI  - A comparison of eight methods for the dual-endpoint evaluation of efficacy in a
      proof-of-concept HIV vaccine trial.
AB  - To support the design of the world's first proof-of-concept (POC) efficacy trial
      of a cell-mediated immunity-based HIV vaccine, we evaluate eight methods for
      testing the composite null hypothesis of no-vaccine effect on either the
      incidence of HIV infection or the viral load set point among those infected,
      relative to placebo. The first two methods use a single test applied to the
      actual values or ranks of a burden-of-illness (BOI) outcome that combines the
      infection and viral load endpoints. The other six methods combine separate tests
      for the two endpoints using unweighted or weighted versions of the two-part z,
      Simes', and Fisher's methods. Based on extensive simulations that were used to
      design the landmark POC trial, the BOI methods are shown to have generally low
      power for rejecting the composite null hypothesis (and hence advancing the
      vaccine to a subsequent large-scale efficacy trial). The unweighted Simes' and
      Fisher's combination methods perform best overall. Importantly, this conclusion
      holds even after the test for the viral load component is adjusted for bias that
      can be introduced by conditioning on a postrandomization event (HIV infection).
      The adjustment is derived using a selection bias model based on the principal
      stratification framework of causal inference.

PMID- 16984334
TI  - Estimation of the causal effects on survival of two-stage nonrandomized treatment
      sequences for recurrent diseases.
AB  - In the treatment of cancer, patients commonly receive a variety of sequential
      treatments. The initial treatments administered following diagnosis can vary, as
      well as subsequent salvage regimens given after disease recurrence. This article
      considers the situation where neither initial treatments nor salvage treatments
      are randomized. Assuming there are no unmeasured confounders, we estimate the
      joint causal effects on survival of initial and salvage treatments, that is, the
      effects of two-stage treatment sequences. For each individual treatment sequence,
      we estimate the survival distribution function and the mean restricted survival
      time. Different treatment sequences are then compared using these estimates and
      their corresponding covariances. Simulation studies were conducted to evaluate
      the performance of the methods, including their sensitivity to the violation of
      the assumption of no unmeasured confounders. The methods are illustrated by a
      retrospective study of patients with soft tissue sarcoma, which motivated this
      research.

PMID- 16984335
TI  - A sequential stratification method for estimating the effect of a time-dependent
      experimental treatment in observational studies.
AB  - Survival analysis is often used to compare experimental and conventional
      treatments. In observational studies, the therapy may change during follow-up and
      such crossovers can be summarized by time-dependent covariates. Given the ever
      increasing donor organ shortage, higher-risk kidneys from expanded criterion
      donors (ECD) are being transplanted. Transplant candidates can choose whether to
      accept an ECD organ (experimental therapy), or to remain on dialysis and wait for
      a possible non-ECD transplant later (conventional therapy). A three-group time
      dependent analysis of such data involves estimating parameters corresponding to
      two time-dependent indicator covariates representing ECD transplant and non-ECD
      transplant, each compared to remaining on dialysis on the waitlist. However, the
      ECD hazard ratio estimated by this time-dependent analysis fails to account for
      the fact that patients who forego an ECD transplant are not destined to remain on
      dialysis forever, but could subsequently receive a non-ECD transplant. We propose
      a novel method of estimating the survival benefit of ECD transplantation relative
      to conventional therapy (waitlist with possible subsequent non-ECD transplant).
      Compared to the time-dependent analysis, the proposed method more accurately
      characterizes the data structure and yields a more direct estimate of the
      relative outcome with an ECD transplant.

PMID- 16984336
TI  - Estimation of the mean from sums with unknown numbers of summands.
AB  - Using dye intensity measurements at synaptic terminals to examine
      neurotransmitter release leads to the problem of estimating an expectation when,
      instead of observing independent random variables with the same expectation, one
      observes, with error, independent random sums of independent variables with the
      same expectation--but with the number of summands in the random sums unobserved.
      Here, a relatively convenient nonparametric approach to estimation is presented.
      Data from an experiment in which cationic styrylpyridinium dye FM4-64 was used in
      cultured mouse hippocampal neurons are used to illustrate the approach.

PMID- 16984337
TI  - Multivariate extensions of McNemar's test.
AB  - This article considers global tests of differences between paired vectors of
      binomial probabilities, based on data from two dependent multivariate binary
      samples. Difference is defined as either an inhomogeneity in the marginal
      distributions or asymmetry in the joint distribution. For detecting the first
      type of difference, we propose a multivariate extension of McNemar's test and
      show that it is a generalized score test under a generalized estimating equations
      (GEE) approach. Univariate features such as the relationship between the Wald and
      score tests and the dropout of pairs with the same response carry over to the
      multivariate case and the test does not depend on the working correlation
      assumption among the components of the multivariate response. For sparse or
      imbalanced data, such as occurs when the number of variables is large or the
      proportions are close to zero, the test is best implemented using a bootstrap,
      and if this is computationally too complex, a permutation distribution. We apply
      the test to safety data for a drug, in which two doses are evaluated by comparing
      multiple responses by the same subjects to each one of them.

PMID- 16984338
TI  - Approaches for calculating power for case-cohort studies.
AB  - An approach for determining the power of a case-cohort study for a single binary
      exposure variable and a low failure rate was recently proposed by Cai and Zeng
      (2004, Biometrics 60, 1015-1024). In this article, we show that computing power
      for a case-cohort study using a standard case-control method yields nearly
      identical levels of power. An advantage of the case-control approach is that
      existing sample size software can be used for the calculations. We also propose
      an additional formula for computing the power of a case-cohort study for the
      situation when the event is not rare.

PMID- 16984340
TI  - On identifiability in capture-recapture models.
AB  - We study the issue of identifiability of mixture models in the context of capture
      recapture abundance estimation for closed populations. Such models are used to
      take account of individual heterogeneity in capture probabilities, but their
      validity was recently questioned by Link (2003, Biometrics 59, 1123-1130) on the
      basis of their nonidentifiability. We give a general criterion for
      identifiability of the mixing distribution, and apply it to establish
      identifiability within families of mixing distributions that are commonly used in
      this context, including finite and beta mixtures. Our analysis covers binomial
      and geometrically distributed outcomes. In an example we highlight the difference
      between the identifiability issue considered here and that in classical binomial
      mixture models.

PMID- 16984342
TI  - Apoptosis-independent poor morphology of bovine embryos produced by multiple
      ovulation.
AB  - In multiple ovulation and embryo transfer (MOET) programmes in cattle, a
      considerable number of morphologically poor-quality embryos continue to be
      produced; this is one of the limiting factors of the technique. Apoptosis has
      often been implicated in developmental arrest and fragmentation; these are
      regarded as poor traits of embryonic quality in mammalian pre-implantation
      embryos. In the present study, apoptosis was assessed in morphologically poor
      quality embryos in comparison with good-quality embryos that were recovered from
      a MOET programme. Retarded embryos (two to 16 cell stage), morulae with severe
      fragmentation and morphologically good-quality morulae recovered from
      superstimulated cows at day 7 post-insemination were subjected to TdT-mediated
      dUTP nick-end labelling (TUNEL) and Hoechst staining. Cell nuclei that showed
      both TUNEL staining and apoptotic morphology were considered to be apoptotic.
      Apoptotic index (AI) was calculated as the percentage of apoptotic cells per
      embryo. Fifteen of 17 retarded embryos and 10 of 15 morphologically poor-quality
      morulae did not show signs of apoptosis. The mean AIs in the morphologically poor
      quality embryos (two to 16 cell stage, 2.2%; poor morulae, 1.3%) were as low as
      that in the good-quality embryos (2.9%). These results suggest that another mode
      of developmental arrest and/or fragmentation that is independent of apoptosis
      occurs in morphologically poor-quality embryos recovered from MOET programmes.

PMID- 16984343
TI  - Effects of constant, 9 and 16-h light cycles on sperm quality, semen storage
      ability and motile sperm subpopulations structure of boar semen.
AB  - This study was performed to test the effect that two separate, daily, constant
      light regimes of both 9 and 16 h could have on the main parameters of boar-semen
      quality analysis, as well as on the motile sperm subpopulations structure and the
      ability of its conservation at 16 degrees C. Results show that both luminous
      regimes have slight, specific effects on the main parameters of boar-semen
      quality analysis, as well as on the motile sperm subpopulations structure.
      Furthermore, the conservation ability at 16 degrees C of boar semen was not
      significantly different between both photoperiods. When a temporal study was
      performed, results showed that semen quality and motility parameter changes were
      stabilized at nearly constant values from the second month of the study to the
      last month in both luminous regimes, indicating a rapid light-related effect on
      testicular function. Our results indicate that light regimes oscillating from 9 h
      daily to 16 h daily are of little importance in the control of boar-semen quality
      in a farming environment.

PMID- 16984344
TI  - In vitro effect of zearalenone and alpha-zearalenol on boar sperm characteristics
      and acrosome reaction.
AB  - This study was conducted to determine the in vitro effects of three different
      concentrations (125, 187.5 and 250 microM in diluted semen) of zearalenone (zen)
      and alpha-zearalenol (alpha-zen) on boar sperm. Semen parameters such as
      motility, viability and spontaneous acrosome reaction were evaluated. From the
      results it was shown that both zen and alpha-zen affected the sperm
      characteristics significantly (p < 0.05), except for alpha-zen at the low
      concentration which did not decrease the percentage of live reacted spermatozoa
      significantly. In conclusion, zen and alpha-zen are directly toxic when they
      affect boar semen in vitro and consequently decrease the fertilization ability of
      the sperm. The higher the concentration of mycotoxin tested, the greater the
      decline of sperm parameters noticed. The influence of mycotoxins was found to be
      time- and dose-dependent.

PMID- 16984345
TI  - Follicle ablation improves the ovarian response and the number of collected
      embryos in superovulated cows during the early stages of lactation.
AB  - A field study was designed to compare ovarian response and embryo yield in cows
      during early lactation when gonadotropin administration followed one of four
      treatments. In group 1A (n = 19) and 1B (n = 9), the estrouses were synchronized
      by two prostaglandin F2alpha (PG) injections given 11 days apart, and starting
      from day 9 of the synchronized cycle superovulation was conducted with eight
      decreasing dose of FSH. In group 1B, ablation of all follicles >3 mm was carried
      out on day 8. In group 2A and 2B (each n = 9), a progesterone plus oestradiol
      intravaginal device (PRID) was inserted for 11 days and gonadotropin
      administration started on day 9, while cows from group 2B had a follicle ablation
      on day 8. In all groups, two PG injections were given along with the sixth and
      the seventh dose of FSH, and the cows were twice inseminated 12 and 24 h after
      estrus detection. Embryos were collected on day 7. In cumulative results from
      aspirated and non-aspirated cows, follicular ablation significantly improved: the
      ovarian response (10 +/- 1.23 vs 6.69 +/- 0.60 corpora lutea per donor), the mean
      collected embryos (6.57 +/- 0.94 vs 2.46 +/- 0.53) and the mean transferable
      embryos (4.43 +/- 0.89 vs 2.18 +/- 0.47). Group 1B and 2B cows had better ovarian
      response than 1A (6.44 +/- 0.81, 12.25 +/- 4.11 and 9.44 +/- 0.93, for groups 1A,
      1B and 2B, respectively, p < 0.05). Similarly, from groups 1B and 2B more (p <
      0.05) embryos were collected in comparison with their respective group, while the
      mean transferable embryos from group 2B (5.22 +/- 1.13) was greater (p < 0.05)
      than that of group 1A (1.67 +/- 0.35), and tented to be greater than those of
      groups 2A (3.44 +/- 1.19, p = 0.062) and 1B (3.00 +/- 1.78, p = 0.066). The
      highest (p < 0.05) transferable embryo collection rate was recorded in group 2B
      (55.29%), followed by that of group 1B (41.33%). In summary, early in lactation,
      an acceptable number of transferable embryos can be collected from high producing
      dairy cows, when follicle ablation prior to superovulation is combined with
      progesterone and oestradiol administration.

PMID- 16984346
TI  - A three-step statistical procedure to identify sperm kinematic subpopulations in
      canine ejaculates: changes after cryopreservation.
AB  - Strong evidences suggest that many different sperm subpopulations co-exist within
      the mammalian ejaculate. These subpopulations have been identified in a number of
      species; however, to the best of our knowledge, no data exist regarding the
      existence of sperm subpopulations within the canine ejaculate. Ejaculates were
      obtained by masturbation from four mongrels and processed using a standard
      freezing protocol. Motility data were analysed before and after cryopreservation
      using a computer assisted sperm analysis (CASA) system ISAS. On raw data, a
      principal component analysis (PCA) was performed to reduce the number of motility
      descriptors to a few informative variables, and then a K-means cluster procedure
      was performed and then a regression analysis to validate the clusters obtained in
      the second analysis. ANOVAs and chi-squared analyses were used to compare
      clusters and males. PCA revealed that two principal components represented more
      that the 88% of the variance with eigenvalues of 3.25 and 3.02, respectively. The
      clustering and discriminant analysis using curvilinear velocity and linear
      velocity as variables revealed the existence of 11 sperm subpopulations--four of
      them characterized by high velocities, two by medium values and five by low
      velocities. After freezing-thawing, nine subpopulations were found--four of high
      velocities, two of medium and three of low velocities. It is concluded that
      freezing-thawing not only impairs sperm motility but also produces changes in the
      sperm subpopulation structure in the canine ejaculate, that the evaluation of the
      sperm structure subpopulations is a better indicator of semen quality and
      freezeability than the use of mean values, and that two sperm motility quality
      indexes can be used to resume of the variables obtained from the CASA analysis.

PMID- 16984347
TI  - An ultrasonographic method to study reproductive seasonality in ewes isolated
      from rams.
AB  - In studies concerning the seasonality in sheep, the effect of the teaser-ram,
      which can by itself induce oestrus as well as the development of ovary function
      bodies, has not been considered. In this study, a method is developed to
      determine ovarian activity during the year while excluding a possible influence
      of the ram. The study was carried out on 10 German Blackhead Mutton ewes (GBM)
      and 10 German Mutton Merino ewes (GMM) and lasted for 14 months. The ewes were
      kept without contact with any ram, and once a week a transrectal ultrasonography
      was conducted to determine ovary function bodies (corpora lutea, follicles) and a
      blood sample was taken to analyse progesterone (P4) concentration. In both
      breeds, the number of ovulating ewes, the ovulation rate (OR), the size of the
      corpora lutea (CL) and P4-concentrations showed significant seasonal
      fluctuations. During the main breeding period (September-February), the OR was
      higher (2.0 +/- 0.4) than during the rest of the year (1.6 +/- 0.5). Outside the
      main breeding season (March-August), approximately 40% GBM ewes and only
      approximately 15% GMM ewes produced CL. The cycle and the related seasonal
      changes in the P4-concentration coincide with different ultrasonically diagnosed
      CL (developing or regressing, insufficient, no CL). Between the volume of fully
      developed CL and P4-concentration, correlations of 0.57 (GMM) and 0.45 (GBM),
      respectively, were found. On average, P4-concentration in September to February
      was by approximately 1.60-1.66 nmol/l in the GMM and by approximately 1.80-1.86
      nmol/l in the GBM higher than in spring and summer. Considering the OR, the P4
      values corresponded with the CL volumes, i.e. in the months from August to
      February the CL values were significantly larger than in the months March to
      August. The ultrasonic ovarian diagnosis is a useful method to determine the ram
      uninfluenced seasonality of reproduction in sheep.

PMID- 16984348
TI  - Influence of the freezing technique (nitrogen liquid vs ultrafreezer of -152
      degrees C) and male-to-male variation over the semen quality in Canarian Mastiff
      breed dogs.
AB  - This study was carried out to assess the in vitro quality of canine semen frozen
      in an ultrafreezer at -152 degrees C and to evaluate the male-to-male variation
      of frozen semen in five male dogs of the Canarian Mastiff breed. Four ejaculates
      of each dog were processed individually (5% glycerol and 0.5% Equex) to reach a
      final concentration of 100 x 10(6) spermatozoa/ml. Then, two freezing techniques
      were tested to assess the seminal quality (sperm motility, live spermatozoa and
      abnormal sperm cell percentages) at 1, 30, 60, 120 and 360 days after freezing:
      (i) semen was frozen and stored in liquid nitrogen; (ii) semen was frozen and
      stored in the ultrafreezer at -152 degrees C. After freezing-thawing, both
      freezing protocols showed no significant differences in sperm motility and the
      percentages of live and abnormal spermatozoa. On the other hand, the microscopic
      characteristics of spermatozoa in fresh semen were practically similar among
      males; however, after the semen processing and freezing, significant differences
      were observed (p < 0.05) among males, especially as regards sperm motility. This
      inter-individual variability was detected in both freezing protocols, showing
      that the male-to-male variation in the seminal quality post-freezing was
      independent of the freezing technique used. The in vitro results obtained in the
      Canarian Mastiff breed confirmed that the use of ultra-freezers at -152 degrees C
      is a potential alternative to liquid nitrogen for storing canine semen for long
      periods of time.

PMID- 16984349
TI  - Pathological conditions of the reproductive organs of male stray dogs in the
      tropics: prevalence, risk factors, morphological findings and testosterone
      concentrations.
AB  - The objective of this study was to estimate the prevalence of and risk factors
      for pathological conditions of the reproductive organs in stray dogs under
      tropical conditions. Three hundred and eighteen dogs were examined post-mortem in
      the period from 1 July 2002 to 30 June 2003. Before killing, a blood sample (from
      the cephalic vein) for testosterone assay was taken. Pathological conditions of
      the reproductive organs were found in 135 of the dogs (42.5%) and in 175 of the
      testes (64.8%). The most frequent pathologies found were testicular degeneration,
      cryptorchidism, testicular hypoplasia and testicular tumours (in 15.1%, 6.6%,
      6.6% and 5.4% of the dogs and 15.1, 4.6, 6.0 and 3.5 of the testes,
      respectively). Transmissible venereal tumour (TVT) was seen in 5.4% of the dogs.
      Testicular degeneration was more common in old dogs and underweight dogs (p <
      0.05). Testicular tumours were 14.3 times more common in cryptorchid dogs. Age
      was another important factor for the development of testicular tumours (p <
      0.05). Lower levels of testosterone concentration (p < 0.05) were observed in
      dogs with advanced testicular degeneration (0.7 +/- 0.8 nM), dogs with
      hypoplastic testicles (0.8 +/- 0.9 nM) and dogs with one degenerated and one
      retained testis or with bilateral cryptorchidism (1.2 +/- 0.9 nM) compared to
      dogs with one or two normal testes (7.0 +/- 5.5 nM). Testicular volume and weight
      were significantly lower in degenerated, hypoplastic and retained testes compared
      with the contralateral normal testis. Some spermatogenic activity was found in
      three of the retained testes, producing oligozoospermic smears with a high
      percentage of sperm abnormalities. No comparable epidemiological data about male
      pathological conditions of the reproductive organs in the dog is available. The
      prevalence found in this study, yet, appears high.

PMID- 16984350
TI  - Accuracy of trans-abdominal ultrasound pregnancy diagnosis in sows using a linear
      or sector probe.
AB  - The assessment of an early and reliable pregnancy diagnosis in sows is very
      important for limiting the number of non-productive days in sow herds. The aim of
      the present study was to investigate the accuracy of trans-abdominal ultrasound
      detection for early pregnancy diagnosis in sows under field conditions.
      Particular attention was paid to the time when a reliable diagnosis can be made,
      and to possible differences between two commonly used types of scanners. In
      total, 202 sows from two herds were tested daily with scanners A (linear
      transducer of 5 MHz) and B (sector transducer of 3.5 MHz) from day 16 until 25
      after insemination. Ninety-three percentage of the sows were pregnant 36 days
      after insemination. Using ultrasound, the first pregnancy could be detected
      already 18 days after insemination. The sensitivity, specificity and overall
      accuracy were higher than 95% from day 24 (scanner A) or day 23 (scanner B) post
      insemination onwards. The positive predictive values from day 19 onwards were
      consistently higher than 95% with both types of scanners, whereas the negative
      predictive values were consistently low for both scanners during the entire
      period. The sensitivity of testing tended to be slightly lower in sows with a
      litter size of <10 total born piglets, compared to sows with 10 or more piglets.
      In conclusion, pregnancy diagnosis in sows using trans-abdominal ultrasound
      testing can be assessed quickly and reliably under field conditions from day 23
      of gestation onwards. Predictive values of positive test results were high in
      these herds, whereas those of negative test results were low. This implies that
      sows with a negative test result early in pregnancy should be retested later.

PMID- 16984351
TI  - In vitro growth and maturation of caprine oocytes.
AB  - This study was conducted to culture in vitro caprine pre-antral follicles for
      determining the competence of growth and maturation of oocytes and establishing a
      suitable culture system for oocyte maturation from pre-antral follicles. Two
      different culture methods (microdrop and agar gel clot) were employed to culture
      caprine pre-antral follicles. The pre-antral follicles were isolated from
      prepubertal goat ovaries by treatment with collagenase and DNase. The isolated
      pre-antral follicles were cultured in basic culture medium for 9 days (for
      growth). And oocytes were cultured in maturation culture medium for another 2
      days for maturation. The result demonstrated that the growth rate of oocytes
      cultured in microdrops was significantly (p < 0.05) higher than that in agar gel
      clots, whereas the viability of oocytes in microdrops was considerably (p < 0.05)
      lower than that in agar gel clots. The oocytes grew over 150 microm in diameter,
      and two of 151 oocytes cultured in microdrops yielded morphologically abnormal
      first polar bodies. However, the size of oocytes cultured in agar gel approached
      to 120 microm in diameter and no polar body was produced.

PMID- 16984352
TI  - Ovarian activity and oestrous signs among group-housed, lactating sows: influence
      of behaviour, environment and production.
AB  - Animal welfare concerns require the development of housing systems that allow the
      animals to express their natural behaviour. One example of this is the group
      housing system for lactating sows. The present study aimed at exploring ovarian
      activity in such a system. Thirty-eight sows farrowing individually outdoors
      during spring and summer, and indoors during autumn and winter, and group-housed
      in groups of four during weeks 3-7 of the lactation period, were monitored
      regarding reproductive functions, behaviour and production during their first to
      fourth lactation period. Average ovulation frequency during lactation was 47%.
      Only 50% of these ovulating cases were accompanied by a standing oestrus.
      Lactational ovulation frequency was higher in later parities (p < 0.001).
      Ovulation frequency was higher (p < 0.05) during winter (74%) and spring (69%),
      than during summer (10%) and autumn (23%). Occurrence of lactational ovulation
      was associated with some aspects of suckling behaviour and also with litter
      weight gain (p < 0.05). Forty-nine per cent of the lactational ovulations
      occurred during the seventh week of lactation. Timing of ovulation seemed
      positively (p = 0.08) associated with weight loss during lactation. Compared with
      the sows that were anoestrus during lactation, oestradiol-17beta values were
      higher (p < 0.05) only in the week before occurrence of lactational ovulation.
      Weaning-to-oestrous interval was prolonged (p < 0.05) among the sows that
      ovulated during lactation. The present study identifies several factors
      influencing ovarian activity among group-housed sows, thereby providing tools for
      the control of lactational ovulation in group-housing systems.

PMID- 16984353
TI  - The influence of pre- and post-ovulatory insemination and early pregnancy on the
      infiltration by cells of the immune system in the sow oviduct.
AB  - The aim of this study was to investigate the influence of pre- and post-ovulatory
      insemination and early pregnancy on the distribution of immune cells in the
      oviduct. Eighteen sows were pre-ovulatory and sixteen sows were post-ovulatory
      inseminated and slaughtered at different times, 5-6 h after insemination, 20-25 h
      and approximately 70 h after ovulation, day 11 and day 19. Immediately after
      slaughter, oviductal samples of three different segments (isthmus, ampulla and
      infundibulum) were fixed, embedded in plastic resin and stained with toluidine
      blue or cryofixed and stored in a freezer at -70 degrees C until analysed by
      immunohistochemistry (pre-ovulatory inseminated sows) with an avidin-biotin
      peroxidase method. Quantitative and qualitative examinations of oviductal
      epithelium and subepithelial connective tissue were performed by light
      microscopy. After pre- or post-ovulatory insemination, neutrophils were not
      observed in the oviductal epithelium from any of the segments or groups. The
      numbers of intraepithelial lymphocytes of all sows as well as CD2- and CD3
      positive cells of the pre-ovulatory inseminated sows were higher in the
      infundibulum than in the other segments (p < or = 0.001). In the subepithelial
      connective tissue of the pre-ovulatory inseminated sows, significantly higher
      numbers of lymphocytes (p < or = 0.001) and plasma cells (p < or = 0.001) were
      found in infundibulum than in isthmus. Neutrophils were found mainly in
      infundibulum, the number approximately 40 h after pre-ovulatory insemination was
      significantly higher (p < or = 0.05) than in the other groups and segments.
      Significantly higher numbers of CD2 than CD3-positive cells were found for all
      groups and segments. In the subepithelial connective tissue of post-ovulatory
      inseminated sows, the numbers of lymphocytes was higher (p < or = 0.001) at day
      19 than up to 50 h after insemination and lower (p < or = 0.001) in isthmus than
      in ampulla and infundibulum. Neutrophils were found in infundibulum in almost all
      groups and the number was significantly higher (p < or = 0.05) in the
      infundibulum up to 50 h after insemination than in other segments. In the
      oviductal epithelium, no influence of insemination was found on the presence of
      phagocytes, i.e. neutrophils and macrophages, but on lymphocytes. In the
      infundibular connective tissue, pre-ovulatory insemination had an effect on
      neutrophil distribution, indicating an active immune response to insemination in
      the upper segment. Post-ovulatory insemination changed the oviductal immune cell
      pattern.

PMID- 16984354
TI  - Vitrification of in vitro-produced bovine embryos by addition of ethylene glycol
      in one-step.
AB  - The objective of this study was to simplify two-step addition of cryoprotectant
      for vitrification of bovine embryos by developing a one-step procedure. Survival
      was calculated as a percentage of non-vitrified controls developed from the same
      batch of oocytes. In experiment 1, bovine blastocysts were vitrified following
      one- or two-step addition of cryoprotectant. Exposure of embryos to
      cryoprotectant in one-step resulted in survival rates not significantly lower (p
      > 0.1) than those obtained by two-step addition (85% vs 98%, respectively). Based
      on these results, experiments 2-4 were designed to test one-step addition of
      cryoprotectant more rigorously. Experiment 2 exposed day 7 blastocysts to 6, 7 or
      8 M ethylene glycol for 2.5 or 3.5 min. At 24 h post-vitrification, survival of
      embryos was similar, irrespective of ethylene glycol concentration or exposure
      time (6 M 38%, 7 M 51%, 8 M 59%; 2.5 min 54%, 3.5 min 45%). In experiment 3,
      blastocysts were exposed to 7 M ethylene glycol for shorter times (30 or 60 s);
      30 s exposure resulted in decreased survival (8% vs 31%, p < 0.05). Experiment 4
      concerned one-step addition of cryoprotectant to day 6 bovine morulae, exposed to
      7 M ethylene glycol for 1 or 1.5 min. There was no difference in survival between
      exposure times of 1 or 1.5 min (28% vs 45%, respectively; p > 0.1). It is unclear
      why many embryos survive vitrification with one-step addition of cryoprotectant,
      but others do not. Although, one-step addition of cryoprotectant simplifies the
      vitrification procedure, survival rates were inadequate for routine
      cryopreservation of in vitro-produced bovine embryos.

PMID- 16984355
TI  - The effect of dose and route of administration of R-cloprostenol on the
      parturient response of sows.
AB  - The aims of the present study were to further examine the efficacy of different
      doses and routes of R-cloprostenol administration on the parturition response in
      sows. Fifty crossbred multiparous sows (Landrace x Yorkshire) with an average
      parity number of 4.7 +/- 2.4 were allocated to induce farrowing by one of the
      following treatments: Group I (control, n = 10) injection with normal saline 2 ml
      administered intramuscularly (i.m.); Group II (n = 10) injection with 75 microg
      of R-cloprostenol administered i.m. (at 7 AM); Group III (n = 10) injection with
      75 microg of R-cloprostenol (at 7 AM) together with 10 IU of oxytocin (24 h after
      injection of R-cloprostenol) administered i.m.; Group IV (n = 10) injection with
      37.5 microg of R-cloprostenol (at 7 AM) administered into perivulva region; Group
      V (n = 10) injection with 37.5 microg of R-cloprostenol (at 7 AM) administered
      into perivulva region together with 10 IU of oxytocin (24 h after injection of R
      cloprostenol) administered i.m. The following parameters: pre-farrowing maternal
      behaviour, restless behaviour, R-cloprostenol or oxytocin injection to farrowing
      interval, expulsion intervals, duration of farrowing, total number of piglets
      born, litter birthweight, umbilical cord morphology and the degree of meconium
      staining were record. There were no significant differences among groups for the
      pre-farrowing maternal behaviours. In all the sows, the restless behaviour was
      not observed. There were no significant effect of oxytocin administration (10 IU,
      i.m.) on the percentage of umbilical cord morphology and the degree of meconium
      staining in different groups. There were no significant effect of route and dose
      of administration on the number of total piglet born, piglet born alive,
      stillbirth, mummy and litter birthweight. No significant effects of the different
      groups were found on the R-cloprostenol and oxytocin injection to farrowing
      interval, expulsion interval and farrowing duration. In conclusion, the present
      results demonstrated that a half dose (37.5 microg) of R-cloprostenol
      administered into the perivulva region was effective for inducing farrowing as
      the full recommended dose (75 microg) administered into the neck region (i.m.)
      and with no restless behaviour.

PMID- 16984370
TI  - Nucleophosmin: a versatile molecule associated with hematological malignancies.
AB  - Nucleophosmin (NPM) is a nucleolar phosphoprotein that plays multiple roles in
      ribosome assembly and transport, cytoplasmic-nuclear trafficking, centrosome
      duplication and regulation of p53. In hematological malignancies, the NPM1 gene
      is frequently involved in chromosomal translocation, mutation and deletion. The
      NPM1 gene on 5q35 is translocated with the anaplastic lymphoma kinase (ALK) gene
      in anaplastic large cell lymphoma with t(2;5). The MLF1 and RARA genes are fused
      with NPM1 in myelodysplastic syndrome and acute myeloid leukemia (AML) with
      t(3;5) and acute promyelocytic leukemia with t(5;17), respectively. In each fused
      protein, the N-terminal NPM portion is associated with oligomerization of a
      partner protein leading to altered signal transduction or transcription.
      Recently, mutations of exon 12 have been found in a significant proportion of de
      novo AML, especially in those with a normal karyotype. Mutant NPM is localized
      aberrantly in the cytoplasm, but the molecular mechanisms for leukemia remain to
      be studied. Studies of knock-out mice have revealed new aspects regarding NPM1 as
      a tumor-suppressor gene. This review focuses on the clinical significance of the
      NPM1 gene in hematological malignancies and newly discovered roles of NPM
      associated with oncogenesis.

PMID- 16984371
TI  - Personalized peptide vaccines: a new therapeutic modality for cancer.
AB  - Therapeutic cancer vaccines have enjoyed little success so far, although many
      clinical trials have been conducted. Therefore, the creation of new protocols
      capable of inducing an objective response is required. We examined two of these
      protocols in the present review. The first is a personalized protocol to take
      into account the immunological diversity of cytotoxic T lymphocyte responses
      among patients. The second is a combination therapy designed to adapt to the
      presence of major histocompatibility complex (MHC)-loss cancer cells. The
      objective response rates of our classical (non-personalized) peptide vaccines
      were 0%, whereas that of personalized vaccines was 11.1% in the total advanced
      cancers and > or = 20% in malignant glioma and cervical cancers, respectively. A
      > or = 50% decrease in serum prostate-specific antigen (PSA) was seen in 8.7% of
      advanced hormone refractory prostate cancer patients by personalized vaccination
      alone, whereas such a decrease was seen in 54% of patients when the personalized
      vaccination was combined with a low dose of estramustine. Based on these
      experiences, we propose a personalized peptide vaccine combined with chemotherapy
      as a new treatment modality for cancers.

PMID- 16984372
TI  - Molecular functions and biological roles of hepatitis B virus x protein.
AB  - Chronic infection of hepatitis B virus (HBV) is one of the major causes of
      hepatocellular carcinoma (HCC) in the world. Hepatitis B virus X protein (HBx)
      has been long suspected to be involved in hepatocarcinogenesis, although its
      oncogenic role remains controversial. HBx is a multifunctional regulator that
      modulates transcription, signal transduction, cell cycle progress, protein
      degradation pathways, apoptosis, and genetic stability by directly or indirectly
      interacting with host factors. This review focuses on the biological roles of HBx
      in HBV replication and cellular transformation in terms of the molecular
      functions of HBx. Using the transient HBV replication assay, ectopically
      expressed HBx could stimulate HBV transcription and replication with the X
      defective replicon to the level of those with the wild one. The transcription
      coactivation is mainly contributing to the stimulatory role of HBx on HBV
      replication although the other functions may affect HBV replication. Effect of
      HBx on cellular transformation remains controversial and was never addressed with
      human primary or immortal cells. Using the human immortalized primary cells, HBx
      was found to retain the ability to overcome active oncogene RAS-induced
      senescence that requires full-length HBx. At least two functions of HBx, the
      coactivation function and the ability to overcome oncogene-induced senescence,
      may be cooperatively involved in HBV-related hepatocarcinogenesis.

PMID- 16984373
TI  - Development of an orthotopic transplantation model in nude mice that simulates
      the clinical features of human lung cancer.
AB  - The objective of the present study was to establish an orthotopic tumor
      transplantation model in nude mice that closely resembles the clinical features
      of human lung cancer. The human lung adenocarcinoma A549 cell line and the
      squamous cell carcinoma SQ5 cell line were used. Tumor cells suspended in serum
      free medium were injected directly into the main bronchi of anesthetized female
      Balb/c athymic nude mice (7-9 weeks old) with or without simultaneous
      administration of 0.01 M ethylenediaminetetracetic acid (EDTA). In some
      experiments, lung carcinoma cells harvested from tumors transplanted
      subcutaneously were recultured and used for intratracheal implantation. Tumor
      nodules that formed in the lung were counted and confirmed by histological
      examination. Administration of A549 cells with EDTA resulted in a 70% engraftment
      rate (n = 10). Recultured A549 cells without and with EDTA resulted in 20% (n =
      5) and 80% (n = 5) engraftment rates, respectively. Administration of SQ5 cells
      without or with EDTA formed 50% (n = 4) and 67% (n = 6) engraftment rates,
      respectively. Recultured SQ5 cells with EDTA further increased the engraftment
      rate to 100% (n = 6). Multiple tumors formed mainly in the left lung and the
      upper lobe of the right lung. Simultaneous administration of EDTA resulted in
      greater numbers of tumor nodules in the lung. Histological findings revealed that
      A549 tumor nodules were distributed primarily in alveoli. The SQ5 solid tumors
      invaded bronchioles and occupied the alveoli. This reproducible orthotopic
      transplantation model produced tumor growth that simulated the clinical features
      of human lung cancer.

PMID- 16984375
TI  - Helicobacter pylori infection stimulates intestinalization of endocrine cells in
      glandular stomach of Mongolian gerbils.
AB  - Intestinal metaplasia has been investigated extensively as a possible
      premalignant condition for stomach cancer but its pathogenesis is still not fully
      understood. In the present study, we examined the relationship between endocrine
      and mucous cell marker expression periodically after Helicobacter pylori
      infection in the Mongolian gerbil model. The numbers of chromogranin A (CgA)
      positive, gastrin-positive and gastric inhibitory polypeptide (GIP)-positive
      cells in H. pylori-infected groups was increased significantly compared with the
      non-infected case. However, CgA-positive and gastrin-positive cells then
      decreased from 50 through 100 experimental weeks after H. pylori infection,
      whereas GIP-positive cells increased. Coexistence of gastrin-positive and GIP
      positive cells was detected in the same gastric and intestinal mixed phenotypic
      glandular-type glands. In conclusion, the endocrine cell phenotype is in line
      with that of the mucous counterpart in the glands of H. pylori-infected Mongolian
      gerbil stomach, supporting the concept that development of intestinal metaplasia
      is due to the abnormal differentiation of a stem cell.

PMID- 16984374
TI  - Suppression of azoxymethane-induced colon cancer development in rats by a
      cyclooxygenase-1 selective inhibitor, mofezolac.
AB  - We demonstrated recently that mofezolac, a cyclooxygenase-1 (COX-1) selective
      inhibitor, suppresses the development of azoxymethane (AOM)-induced colonic
      aberrant crypt foci in F344 rats and intestinal polyps in APC1309 mice. In the
      present study, we therefore investigated the effects of mofezolac on colon cancer
      development. Male F344 rats were injected subcutaneously with 15 mg/kg body
      weight of AOM in the back twice at 7-day intervals from 5 weeks of age, and fed a
      diet containing 600 or 1200 ppm mofezolac for 32 weeks, starting 1 day before the
      first dosing of AOM. Treatment with 1200 ppm mofezolac significantly reduced the
      incidence, multiplicity and volume of colon carcinomas to 79%, 2.15 +/- 1.65 and
      7.5 +/- 11.8 mm3, respectively, compared with 94%, 3.19 +/- 1.87 and 23.7 +/-
      31.2 mm3 in the AOM treatment alone. Administration of 600 ppm mofezolac showed
      only a slight reduction. No side effects were observed in any of the groups.
      These results confirm that COX-1, as well as COX-2, contributes to colon
      carcinogenesis and that mofezolac may be a good chemopreventive agent for human
      colon cancer.

PMID- 16984376
TI  - Lack of enhancement of susceptibility to mammary and thyroid carcinogenesis in
      rats exposed to DMBA and DHPN following prepubertal iodine deficiency.
AB  - Epidemiologic and experimental studies suggest that iodine deficiency increases
      the risk of mammary as well as thyroid cancers, but susceptibility to tumor
      development when this occurs during the prepubertal stage is not completely
      understood. In the present study, we therefore evaluated this question in F344
      rats. Dams during the lactation period and their weaned offspring until postnatal
      week 7 were fed an iodine-free diet. Female offspring were then given 7,12
      dimethylbenz[a]anthracene (DMBA, 50 mg/kg body weight) by gavage for mammary
      tumor induction in week 7. Both the male and female rats were given free access
      to drinking water containing N-bis(2-hydroxypropyl)nitrosamine (DHPN), (0.1 and
      0.2% for male and female rats, respectively) for wide spectrum tumor induction in
      organs, including the thyroid gland, from weeks 7-11. All offspring were killed
      at week 50 for histopathological examination. The iodine deficiency had no
      significant influence on incidences and/or multiplicities of mammary and thyroid
      tumors. Furthermore, tumor induction in the liver, kidney, lung, esophagus and
      urinary bladder was not affected in either sex. The present results thus indicate
      a lack of influence of iodine deficiency condition early in life on subsequent
      carcinogenic susceptibility.

PMID- 16984377
TI  - Role of tumor necrosis factor-alpha and its receptors in human benign breast
      lesions and tumors (in situ and infiltrative).
AB  - The aim of the present study was to characterize the expression pattern of tumor
      necrosis factor (TNF)-alpha and its receptors in breast samples (benign diseases,
      in situ carcinomas and infiltrating carcinomas), and to compare these results
      with those obtained previously for interleukin-6, p53 and p21 using the same
      samples in order to elucidate the effects of these cytokines on the proliferation
      apoptosis equilibrium. Immunoexpression of TNF-alpha and its receptors (TNFRI and
      TNFRII) were studied by western blotting and immunohistochemistry. The percentage
      of samples positive for TNF-alpha and TNFRII was higher in in situ carcinoma than
      in benign breast diseases, and TNFRII was even higher in infiltrating tumors. The
      percentage of samples positive for TNFRI was similar in the three groups. For the
      three proteins and in the three patient groups, immunoreactions were observed in
      the peripheral cytoplasm. In the positive samples, immunostaining for TNF-alpha
      was more intense in infiltrating tumors than in the other two patient groups,
      whereas immunostaining for both receptors was higher in in situ carcinoma than in
      benign breast diseases, and even higher in infiltrating tumors. Comparing the TNF
      alpha results with previous results for mtp53, p21 and interleukin-6, we found an
      association between the expression of these four proteins and increasing
      malignancy. TNF-alpha might be an important factor in breast cancer promotion as
      its proliferation and survival effects seems to be enhanced through the increased
      expression of TNFRII. Also, the pro-apoptotic pathway of TNFRI could be inhibited
      by p21 (which appeared increased in breast cancer), altering TNFRI effects in
      promoting the expression of several factors, such interleukin-6, which contribute
      to tumor promotion.

PMID- 16984378
TI  - Oxygen and glucose consumption in gastrointestinal adenocarcinomas: correlation
      with markers of hypoxia, acidity and anaerobic glycolysis.
AB  - This study gives an insight into tumor metabolic activity by investigating oxygen
      and glucose content, together with their metabolic products carbon dioxide and
      acids-pH, in the arterial and venous blood of a tumor. Nineteen patients with
      gastrointestinal adenocarcinomas undergoing surgery were studied. Biochemical
      analysis showed that in a large subgroup of tumors, oxygen consumption was
      reduced while that of glucose was increased in malignant, as compared to normal
      tissues; these features were more evident in tumors overexpressing lactate
      dehydrogenase (LDH-5) and hypoxia inducible factors (HIF1alpha/2alpha). An
      increase in carbon dioxide production in the tumor environment was linked with
      overexpression of carbonic anhydrase 9 (CA9). The simultaneous overexpression of
      CA9 and LDH-5 was related to very low pH levels in the veins draining the tumor,
      suggesting an intense acidification of the tumor microenvironment in such cases.
      These in vivo data confirm the importance of HIFs and their downstream regulated
      genes in tumor metabolism, particularly in glycolysis and carbon dioxide
      buffering.

PMID- 16984379
TI  - Nuclear expression of S100A4 is associated with aggressive behavior of epithelial
      ovarian carcinoma: an important autocrine/paracrine factor in tumor progression.
AB  - Although S100A4 expression has reportedly been associated with metastasis of
      various malignancies, little is known about its biological significance in
      ovarian carcinomas. In this study, we investigated expression and secretion of
      S100A4 and its extracellular function in ovarian carcinoma cells. We first used
      immunohistochemistry to examine the expression and localization of S100A4 in 113
      epithelial ovarian neoplasms (24 benign, 20 borderline, and 69 malignant tumors)
      and analyzed its prognostic significance in patients with ovarian carcinoma. Then
      we investigated the expression, subcellular localization, and secretion of S100A4
      in four ovarian carcinoma cell lines. Finally, we examined the effect of S100A4
      treatment on the cell proliferation and invasiveness of ovarian carcinoma cells,
      along with activation of small GTPase, RhoA. Both cytoplasmic and nuclear
      expressions of S100A4 were significantly stronger in carcinomas than those in
      benign and borderline tumors. Ovarian carcinoma patients with strong nuclear
      S100A4 expression showed a significantly shorter survival than those without (P =
      0.0045). This was not the case for cytoplasmic S100A4 expression. Ovarian
      carcinoma cell lines were shown to express S100A4, and secrete S100A4 into the
      culture media. Treatment with recombinant S100A4 resulted in the upregulation of
      S100A4 expression, translocation of S100A4 into the nucleus, and enhancement of
      invasiveness, which was associated with the upregulation of small GTPase, RhoA.
      These findings suggest that the nuclear expression of S100A4 is involved in the
      aggressive behavior of ovarian carcinoma and S100A4 is an autocrine/paracrine
      factor that plays an important role in the aggressiveness of ovarian carcinoma
      cells.

PMID- 16984380
TI  - Identification of oligopeptides binding to peritoneal tumors of gastric cancer.
AB  - This is a report of in vivo intraperitoneal biopanning, and we successfully
      identified a novel peptide to target the multiple peritoneal tumors of gastric
      cancer. A phage display library was injected directly into the abdominal cavity
      of mice bearing peritoneal tumors of human gastric cancer, and phages associated
      with the tumors were subsequently reclaimed from isolated samples. The tumor
      associated phages were amplified and the biopanning cycle was repeated five times
      to enrich for high affinity tumor-selective binding peptides. Finally, a tri
      peptide motif, KLP, which showed homology with laminin 5 (a ligand for
      alpha3beta1 integrin), was identified as a binding peptide for peritoneal tumors
      of gastric cancer. Phage clones displaying the sequence KLP showed 64-fold higher
      binding to peritoneal tumors than control phage and were preferentially
      distributed in tumors rather than in normal organs after intraperitoneal
      injection into mice. In addition, the KLP phages were more likely to bind to
      cancer cells in malignant ascites derived from a patient with recurrent gastric
      cancer. Synthesized peptide containing the motif KLP (SWKLPPS) also showed a
      strong binding activity to peritoneal tumors without cancer growth effect.
      Liposomes conjugated with SWKLPPS peptide appeared significantly more often in
      tumors than control liposomes after intraperitoneal injection into mice.
      Furthermore, modification of liposomes with SWKLPPS peptide enhanced the
      antitumor activity of adriamycin on gastric cancer cells. The peptide motif KLP
      seems a potential targeting ligand for the treatment of peritoneal metastasis of
      gastric cancer.

PMID- 16984381
TI  - Induction of cell apoptosis in non-small cell lung cancer cells by cyclin A1
      small interfering RNA.
AB  - Cyclin A1 and cyclin B1 are overexpressed in various tumors but are present at
      low levels in normal tissues. Cyclin A1 is restricted to germ cells undergoing
      meiosis. In order to explore the possibility of using cyclin A1 and cyclin B1 as
      anticancer targets, we knocked them down in two lung cancer cell lines, H157 and
      H596, using siRNA. As with cyclin A1 siRNA in lung cancer cell lines, cyclin B1,
      Cdc2 and CDK2 were all significantly downregulated. The S phase fraction
      increased significantly, and they eventually underwent apoptosis by way of
      downregulated intrinsic apoptotic pathways and modulators with upregulated
      extrinsic apoptotic pathways. Our study suggests that cyclin A1 might be a
      promising anticancer target specific to lung cancer.

PMID- 16984382
TI  - Role of phosphatidylinositol-3 kinase/Akt pathway in bladder cancer cell
      apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand.
AB  - TRAIL/Apo2L is a pro-apoptotic cytokine that is capable of inducing apoptosis in
      a wide variety of cancer cells but not in normal cells. Among various molecular
      strategies by which cancer cells evade apoptosis, PI3K/Akt signaling represents a
      dominant survival pathway. In this report, we investigated the role of PI3K/Akt
      pathway in TRAIL-induced apoptotic death in human bladder cancer cells. We
      observed that RT4 cells had very low level of constitutively active Akt and were
      sensitive to TRAIL, whereas UM-UC-3 and T24 cells had higher levels of
      constitutively active Akt and were resistant to TRAIL. Downregulation of
      constitutively active Akt by PI3K inhibitors, wortmannin and LY294002, reversed
      cellular resistance to TRAIL. However, transfecting constitutively active Akt
      into RT4 cells increased Akt activity and inhibited TRAIL-induced apoptosis.
      These results suggest that elevated Akt activity protects UM-UC-3 and T24 cells
      from TRAIL-induced apoptosis, and the PI3K/Akt signaling might inhibit apoptotic
      signals. Thus, the modulation of Akt activity by combining pharmacological drugs
      or genetic alterations of the Akt expression could induce cellular responsiveness
      to TRAIL and PI3K/Akt signaling pathway could serve as a novel target for
      therapeutic intervention in bladder cancer.

PMID- 16984383
TI  - Randomized, double-blind, placebo-controlled trial of bovine lactoferrin in
      patients with chronic hepatitis C.
AB  - Several studies have suggested that lactoferrin administration may decrease the
      serum level of hepatitis C virus (HCV) RNA in patients with chronic hepatitis C.
      The aim of the present study was to confirm the efficacy of orally administered
      bovine lactoferrin (bLF) in patients with chronic hepatitis C. The patients with
      chronic hepatitis C randomly received either oral bLF at a dose of 1.8 g daily
      for 12 weeks, or an oral placebo. The primary endpoint was the virologic
      response, defined as a 50% or greater decrease in serum HCV RNA level at 12 weeks
      compared with the baseline. The secondary endpoint was the biochemical response,
      which was defined as a 50% or greater decrease in the serum alanine
      aminotransferase (ALT) level at 12 weeks compared with the baseline. One hundred
      and ninety-eight of 199 patients were evaluable for efficacy and safety. bLF
      treatment was well tolerated and no serious toxicities were observed. A virologic
      response was achieved in 14 of 97 patients (14.4%) in the bLF group, and 19 of
      101 (18.8%) in the placebo group. There was no significant difference in
      virologic response rates between the two groups (-4.4%, 95% confidence interval 
      14.8, 6.1). In addition, bLF intake did not have any favorable effect on the
      serum ALT level. The virologic responses were not different between two groups in
      any subgroup analysis. In conclusion, orally administered bLF does not
      demonstrate any significant efficacy in patients with chronic hepatitis C.

PMID- 16984384
TI  - Small interfering RNA targeting epidermal growth factor receptor enhances
      chemosensitivity to cisplatin, 5-fluorouracil and docetaxel in head and neck
      squamous cell carcinoma.
AB  - Overexpression of epidermal growth factor receptor (EGFR) has been found in
      various epithelial malignancies, including head and neck squamous cell carcinoma
      (HNSCC), and is associated with increased tumor growth, metastasis, resistance to
      chemotherapeutic agents and poor prognosis. As such, EGFR is a potential target
      for antitumor therapy and several EGFR inhibitors have been investigated in
      preclinical or clinical settings. In the present study, we used small interfering
      RNA (siRNA) to downregulate EGFR expression while evaluating the effect of EGFR
      siRNA on cell proliferation, and the combined effects with cisplatin, 5
      fluorouracil (5-FU) and docetaxel in HNSCC. Furthermore, HNSCC xenografts were
      treated with EGFR siRNA alone or in combination with cisplatin, and tumor growth
      was examined. EGFR expression, proliferation, angiogenesis and apoptosis index
      were evaluated by immunohistochemistry. The results showed that EGFR siRNA
      efficiently downregulated EGFR expression and inhibited cell growth of HNSCC.
      Treatment with EGFR siRNA in combination with cisplatin, 5-FU and docetaxel
      enhanced chemosensitivity with a significant increase in apoptosis. EGFR siRNA
      delivered by atelocollagen enhanced the antitumor effect of cisplatin in the
      HNSCC xenograft model. These cumulative results suggest that EGFR siRNA combined
      with cisplatin, 5-FU and docetaxel may be a feasible strategy to enhance the
      effects of chemotherapy in patients with HNSCC.

PMID- 16984385
TI  - High dose calcitriol may reduce thrombosis in cancer patients.
AB  - The incidence of venous and arterial thrombosis in a placebo-controlled
      randomised trial of DN-101 (high dose calcitriol) with docetaxel versus docetaxel
      was compared. Of the 13 thrombotic events observed in the 250 patients enroled in
      this study, two occurred in DN-101 and 11 in placebo-treated patients (P = 0.01).
      This difference remained significant after adjustment for baseline history of
      thrombosis, atrial fibrillation and use of anti-thrombotic agents. In vitro and
      vitamin D receptor (VDR) knockout mouse studies predict that nanomolar
      concentrations of calcitriol may act as an antithrombotic agent. We report the
      first clinical observation that supports this hypothesis in humans.

PMID- 16984386
TI  - Daclizumab, an efficient treatment for steroid-refractory acute graft-versus-host
      disease.
AB  - In a phase II study, daclizumab was given as single second-line agent to 62
      patients with steroid-refractory acute graft-versus-host disease (aGVHD).
      Complete resolution of aGVHD was achieved in 68.8% of patients. This response
      rate was significantly associated with a lower number of involved organs and
      smaller extent of skin involvement. The 4-year event-free survival (EFS) was
      54.6%. Grade > or =III aGVHD, > or =2 involved organs at baseline and patient age
      >18 years were independently associated with lower EFS. Daclizumab could be a
      suitable alternative treatment for aGVHD, particularly when limited to the skin
      or gastrointestinal tract.

PMID- 16984387
TI  - Resolution of ambiguous low-level positive quantitative polymerase chain reaction
      results in TEL-AML1 positive ALL using a post-PCR fluorescent oligoligation
      method.
AB  - The interpretation of low-level or non-reproducible amplification results in
      clinical quantitative polymerase chain reaction (Q-PCR) assays can be difficult
      to definitively resolve. Concerning minimal residual disease detection in
      leukaemia, indeterminate low-level results might create prognostic or therapeutic
      dilemmas. We evaluated low-level, ambiguous Q-PCR results in a study of paired
      diagnostic and end-induction (day 29) TEL-AML1 positive acute lymphoblastic
      leukaemia samples utilising a novel fluorescent primer ligation detection assay.
      The data presented here indicate that a significant number of low-level apparent
      Q-PCR positive results may be spurious or non-specific in nature, requiring
      additional technical manoeuvres for confirmation of true positive cases.

PMID- 16984388
TI  - Discrepancy between impedance and immunofluorescence platelet counting has
      implications for clinical decision making in patients with idiopathic
      thrombocytopenia purpura.

PMID- 16984389
TI  - Haemoglobin-S in sickle cell trait with papillary necrosis.

PMID- 16984391
TI  - Current status of haploidentical stem cell transplantation.
AB  - Haploidentical stem cell transplantation is an alternative transplant strategy
      for patients without an human leucocyte antigen-matched donor. The historical
      experience with haploidentical stem cell transplantation has been characterised
      by the immunological consequences of crossing a major histocompatibility barrier,
      namely graft-versus-host disease (GVHD), graft rejection and impaired immune
      reconstitution. Ex vivo T-cell depletion of the graft may reduce the risk of
      GVHD, but at the expense of a higher risk of engraftment failure and relapse of
      the underlying malignancy. Myeloablative transplant strategies using vigorously T
      cell-depleted 'megadose' stem cells appear to have improved the outcomes of
      selected patients with acute leukaemia. Non-myeloablative stem cell
      transplantation strategies, in which mixed chimaerism as a platform for adoptive
      cellular immunotherapy is intentionally induced, show promise for limiting GVHD
      and lessening transplant-related mortality. Future approaches, based on promising
      preclinical and early clinical observations, may include selective allodepletion
      of the graft, and manipulation of the cellular environment post-transplant using
      selected cellular populations or immunomodulatory soluble factors.

PMID- 16984390
TI  - The risk of recurrent venous thromboembolism in pregnancy and puerperium without
      antithrombotic prophylaxis.
AB  - Whether or not pregnant women with a previous episode of venous thromboembolism
      (VTE) should receive antithrombotic prophylaxis is a matter of debate. In order
      to estimate the rate of recurrent deep venous thrombosis (DVT) or pulmonary
      embolism (PE) during pregnancy and puerperium we retrospectively investigated a
      cohort of 1104 women with previous VTE; after a single DVT or isolated PE, 88 of
      them became pregnant at least once without receiving antithrombotic prophylaxis.
      Overall, 155 pregnancies and 120 puerperium periods without prophylaxis were
      recorded. There were nine recurrences during pregnancy and 10 during puerperium,
      with a rate of 5.8% [95% confidence interval (CI) 3.0-10.6] and 8.3% (95%CI 4.5
      14.6) respectively. In pregnancy, the rate of recurrence was 7.5% (95%CI 4.0
      13.7) if the first VTE was unprovoked, related to pregnancy or to oral
      contraceptive use, whereas no recurrence occurred if the first VTE was related to
      other transient risk factors. In puerperium, the rate of recurrence was 15.5%
      (95%CI 7.7-28.7) in women with a pregnancy-related first VTE, with a risk 3.9
      times higher than in the remaining women. Inherited thrombophilia was not
      associated with a statistically significant increase in risk of recurrence in
      pregnancy or in puerperium, yet the rate of recurrence in puerperium was 14.2%
      (95%CI 5.7-31.4) in overall carriers of factor V Leiden and 30% (95%CI 10.7-60.3)
      in carriers with a pregnancy-related first VTE, with a risk 6.8 times higher than
      in women without thrombophilia and with a non pregnancy-related first VTE.

PMID- 16984392
TI  - Development of autologous cytotoxic CD4+ T clones in a human model of B-cell non
      Hodgkin follicular lymphoma.
AB  - Immunotherapy for cancer aims to generate cytotoxic cells that are capable of
      eradicating tumour cells. It has been well demonstrated that helper, non
      cytotoxic CD4(+) T cells are important for the induction and maintenance of anti
      tumour immunity exerted by cytotoxic CD8(+) T cells. In contrast, the existence
      of direct anti-tumour, effector cytotoxic CD4(+) T cells remains elusive, mainly
      due to the paucity of reliable experimental data, especially in human B-cell non
      Hodgkin lymphomas. This study developed an appropriate, autologous follicular B
      cell non-Hodgkin follicular lymphoma model, including the in vitro establishment
      of a malignant, human leucocyte antigen class I (HLA-I) deficient B-cell line,
      and the generation of three autologous anti-tumour cytotoxic CD4(+) T-cell clones
      originating from the peripheral blood of the same patient. These three clones
      were considered as tumour specific, because they were capable of killing the
      malignant, HLA-I-deficient B-cell line through a classical HLA-II restricted
      perforin-mediated pathway, but did not lyse the Epstein-Barr virus-infected
      autologous normal B lymphocytes. All three CD4(+)clones were T-cell receptor
      Vbeta17-Dbeta1-Jbeta1.2 and exhibited an identical complementarity-determining
      region 3, suggesting the immunodominance of a single peptide antigen presented by
      tumour cells. Such lymphoma models would provide a useful tool for in vivo
      expansion and the adoptive transfer of selected CD4(+) cytotoxic cells in
      immunotherapeutic strategies.

PMID- 16984393
TI  - Structural and thermodynamic insights into the binding mode of five novel
      inhibitors of lumazine synthase from Mycobacterium tuberculosis.
AB  - Recently published genomic investigations of the human pathogen Mycobacterium
      tuberculosis have revealed that genes coding the proteins involved in riboflavin
      biosynthesis are essential for the growth of the organism. Because the enzymes
      involved in cofactor biosynthesis pathways are not present in humans, they appear
      to be promising candidates for the development of therapeutic drugs. The
      substituted purinetrione compounds have demonstrated high affinity and
      specificity to lumazine synthase, which catalyzes the penultimate step of
      riboflavin biosynthesis in bacteria and plants. The structure of M. tuberculosis
      lumazine synthase in complex with five different inhibitor compounds is
      presented, together with studies of the binding reactions by isothermal titration
      calorimetry. The inhibitors showed the association constants in the micromolar
      range. The analysis of the structures demonstrated the specific features of the
      binding of different inhibitors. The comparison of the structures and binding
      modes of five different inhibitors allows us to propose the ribitylpurinetrione
      compounds with C4-C5 alkylphosphate chains as most promising leads for further
      development of therapeutic drugs against M. tuberculosis.

PMID- 16984394
TI  - 7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a
      potential therapeutic target. Characterization and inhibition studies.
AB  - Diaminopelargonic acid aminotransferase (DAPA AT), which is involved in biotin
      biosynthesis, catalyzes the transamination of 8-amino-7-oxononanoic acid (KAPA)
      using S-adenosyl-l-methionine (AdoMet) as amino donor. Mycobacterium tuberculosis
      DAPA AT, a potential therapeutic target, has been overproduced in Escherichia
      coli and purified to homogeneity using a single efficient step on a nickel
      affinity column. The enzyme shows an electronic absorption spectrum typical of
      pyridoxal 5'-phosphate-dependent enzymes and behaves as a homotetramer in
      solution. The pH profile of the activity at saturation shows a single ionization
      group with a pK(a) of 8.0, which was attributed to the active-site lysine
      residue. The enzyme shows a Ping Pong Bi Bi kinetic mechanism with strong
      substrate inhibition with the following parameters: K(mAdoMet) = 0.78 +/- 0.20
      mm, K(mKAPA) = 3.8 +/- 1.0 microm, k(cat) = 1.0 +/- 0.2 min(-1), K(iKAPA) = 14 +/
      2 microm. Amiclenomycin and a new analogue, 4-(4c-aminocyclohexa-2,5-dien-1r
      yl)propanol (referred to as compound 1), were shown to be suicide substrates of
      this enzyme, with the following inactivation parameters: K(i) = 12 +/- 2 microm,
      k(inact) = 0.35 +/- 0.05 min(-1), and K(i) = 20 +/- 2 microm, k(inact) = 0.56 +/-
      0.05 min(-1), for amiclenomycin and compound 1, respectively. The inactivation
      was irreversible, and the partition ratios were 1.0 and 1.1 for amiclenomycin and
      compound 1, respectively, which make these inactivators particularly efficient.
      compound 1 (100 microg.mL(-1)) completely inhibited the growth of an E. coli
      C268bioA mutant strain transformed with a plasmid expressing the M. tuberculosis
      bioA gene, coding for DAPA AT. Reversal of the antibiotic effect was observed on
      the addition of biotin or DAPA. Thus, compound 1 specifically targets DAPA AT in
      vivo.

PMID- 16984395
TI  - Application of a fluorescent cobalamin analogue for analysis of the binding
      kinetics. A study employing recombinant human transcobalamin and intrinsic
      factor.
AB  - Fluorescent probe rhodamine was appended to 5' OH-ribose of cobalamin (Cbl). The
      prepared conjugate, CBC, bound to the transporting proteins, intrinsic factor
      (IF) and transcobalamin (TC), responsible for the uptake of Cbl in an organism.
      Pronounced increase in fluorescence upon CBC attachment facilitated detailed
      kinetic analysis of Cbl binding. We found that TC had the same affinity for CBC
      and Cbl (K(d) = 5 x 10(-15) m), whereas interaction of CBC with the highly
      specific protein IF was more complex. For instance, CBC behaved normally in the
      partial reactions CBC + IF(30) and CBC + IF(20) when binding to the isolated IF
      fragments (domains). The ligand could also assemble them into a stable complex
      IF(30)-CBC-IF(20) with higher fluorescent signal. However, dissociation of IF(30)
      CBC-IF(20) and IF-CBC was accelerated by factors of 3 and 20, respectively, when
      compared to the corresponding Cbl complexes. We suggest that the correct domain
      domain interactions are the most important factor during recognition and fixation
      of the ligands by IF. Dissociation of IF-CBC was biphasic, and existence of
      multiple protein-analogue complexes with normal and partially corrupted structure
      may explain this behaviour. The most stable component had K(d) = 1.5 x 10(-13) m,
      which guarantees the binding of CBC to IF under physiological conditions. The
      specific intestinal receptor cubilin bound both IF-CBC and IF-Cbl with equal
      affinity. In conclusion, the fluorescent analogue CBC can be used as a reporting
      agent in the kinetic studies, moreover, it seems to be applicable for imaging
      purposes in vivo.

PMID- 16984396
TI  - Human enhancer of rudimentary is a molecular partner of PDIP46/SKAR, a protein
      interacting with DNA polymerase delta and S6K1 and regulating cell growth.
AB  - Enhancer of rudimentary (ER) is a small protein that has a unique amino acid
      sequence and structure. Its highly conserved gene has been found in all
      eukaryotic kingdoms with the exception of fungi. ER was proposed to be involved
      in the metabolism of pyrimidines and was reported to act as a transcriptional
      repressor in a cell type-specific manner. To further elucidate ER functions, we
      performed the yeast two-hybrid screen of the human lung cDNA library for clones
      encoding proteins interacting with the human ER protein. The screen yielded
      polymerase delta interacting protein 46 or S6K1 Aly/REF-like target
      (PDIP46/SKAR), a protein possessing one RNA recognition motif (RRM) and being a
      protein partner of both the p50 subunit of DNA polymerase delta and p70 ribosomal
      protein S6 kinase 1 (S6K1). This interaction was further confirmed in vitro by
      the glutathione S-transferase-ER pull-down of a protein of 46 kDa from a nuclear
      extract from human cells which was identified as PDIP46/SKAR by tandem mass
      spectrometry. The bipartite region of PDIP46/SKAR interacting with ER comprising
      residues 274-421 encompasses the docking site for S6K1 within the RRM and two
      serines phosphorylated by S6K1. ER and both isoforms of PDIP46/SKAR share the
      same nuclear localization in the mammalian cells and their genes display a
      ubiquitous pattern of expression in a variety of human tissues, so the
      interaction between ER and PDIP46/SKAR has an opportunity to occur universally in
      mammalian cells. Because PDIP46/SKAR is involved in the regulation of cell growth
      its interaction with ER may suggest some function for ER in that control.

PMID- 16984397
TI  - Rac upregulates tissue inhibitor of metalloproteinase-1 expression by redox
      dependent activation of extracellular signal-regulated kinase signaling.
AB  - The Rho-like GTPase Rac regulates distinct actin cytoskeleton changes required
      for adhesion, migration and invasion of cells. Tiam1 specifically activates Rac,
      and Rac has been shown to affect several signaling pathways in a partly cell-type
      specific manner. Recently, we demonstrated that Rac activation inhibits Matrigel
      invasion of human carcinoma cells by transcriptional upregulation of tissue
      inhibitor of metalloproteinase-1. The purpose of the present study was to
      identify key mediators of Tiam1/Rac-induced tissue inhibitor of metalloproteinase
      1 expression. Mutational analysis of the human tissue inhibitor of
      metalloproteinase-1 promoter revealed a major role for a distinct activating
      protein-1 site at -92/-86 and a minor role for an adjacent polyoma enhancer A3
      site. Moreover, Rac activation induced the generation of reactive oxygen species
      and subsequent reactive oxygen species-dependent activation of extracellular
      signal-regulated kinase 1,2. In contrast, c-Jun N-terminal kinase and p38 mitogen
      activated protein kinase activities were not affected. In line with this,
      Tiam1/Rac-induced tissue inhibitor of metalloproteinase-1 expression as well as
      Tiam1/Rac-induced binding of nuclear extracts to the activating protein-1 site at
      -92/-86 were inhibited by catalase and by specific inhibitors of the
      extracellular signal-related kinase-1,2 activators, mitogen-activated protein
      kinase kinase-1 and mitogen-activated protein kinase kinase-2 (PD098059, U0126).
      In conclusion, Rac-induced transcriptional upregulation of tissue inhibitor of
      metalloproteinase-1 is mediated by reactive oxygen species-dependent activation
      of extracellular signal-related kinase-1,2 and by transcription factors of the
      activating protein-1 family.

PMID- 16984398
TI  - Biochemical and structural analyses of a higher plant photosystem II supercomplex
      of a photosystem I-less mutant of barley. Consequences of a chronic over
      reduction of the plastoquinone pool.
AB  - Photosystem II of higher plants is a multisubunit transmembrane complex composed
      of a core moiety and an extensive peripheral antenna system. The number of
      antenna polypeptides per core complex is modulated following environmental
      conditions in order to optimize photosynthetic performance. In this study, we
      used a barley (Hordeum vulgare) mutant, viridis zb63, which lacks photosystem I,
      to mimic extreme and chronic overexcitation of photosystem II. The mutation was
      shown to reduce the photosystem II antenna to a minimal size of about 100
      chlorophylls per photosystem II reaction centre, which was not further reducible.
      The minimal photosystem II unit was analysed by biochemical methods and by
      electron microscopy, and found to consist of a dimeric photosystem II reaction
      centre core surrounded by monomeric Lhcb4 (chlorophyll protein 29), Lhcb5
      (chlorophyll protein 26) and trimeric light-harvesting complex II antenna
      proteins. This minimal photosystem II unit forms arrays in vivo, possibly to
      increase the efficiency of energy distribution and provide photoprotection. In
      wild-type plants, an additional antenna protein, chlorophyll protein 24 (Lhcb6),
      which is not expressed in viridis zb63, is proposed to associate to this minimal
      unit and stabilize larger antenna systems when needed. The analysis of the mutant
      also revealed the presence of two distinct signalling pathways activated by
      excess light absorbed by photosystem II: one, dependent on the redox state of the
      electron transport chain, is involved in the regulation of antenna size, and the
      second, more directly linked to the level of photoinhibitory stress perceived by
      the cell, participates in regulating carotenoid biosynthesis.

PMID- 16984401
TI  - The Aspergillus fumigatus cellobiohydrolase B (cbhB) promoter is tightly
      regulated and can be exploited for controlled protein expression and RNAi.
AB  - The utility of the Aspergillus fumigatus cellobiohydrolase cbhB promoter for
      controlled gene expression has been investigated. cbhB message was present at
      high levels in the presence of carboxymethylcellulose and undetected in the
      presence of glucose. A reporter construct using the cbhB promoter showed similar
      behaviour and gave lower message levels than the Aspergillus nidulans alcA
      promoter under repressing conditions. An RNAi construct driven by the cbhB
      promoter was used to down-regulate the alb1 gene; transformants showed low alb1
      message levels and a loss-of-function phenotype with carboxymethylcellulose,
      while both wild-type message levels and phenotype were seen with glucose. The
      cbhB promoter is therefore tightly controlled and can be exploited for the study
      of A. fumigatus.

PMID- 16984402
TI  - Analysis of in vivo expressed genes in Mannheimia haemolytica A1.
AB  - The expression of Mannheimia haemolytica A1 genes during in vivo growth was
      examined by reverse transcriptase-polymerase chain reaction (RT-PCR) using total
      RNA extracted directly from M. haemolytica A1 recovered from pneumonic lungs of
      cattle. Primers specific for three groups of genes were used. Group 1 includes
      virulence-related genes: lktC, tbpB, ahs, nmaA, gs60 and gcp. Group 2 includes
      genes that code for putative two-component regulatory systems: narP, narQ, ttrR,
      ttrS, phoB and phoR. Group 3 includes genes involved in regular cellular
      functions such as plp4, thiL and rrf. The RT-PCR data were examined in
      conjunction with the percent pneumonic lesion in each lung scored during
      necropsy. The analysis showed that lungs with a higher percent pneumonic score
      exhibit expression of more M. haemolytica A1 genes. For group 1 genes, lktC was
      expressed in the majority of samples, whereas the other genes were only expressed
      in some samples. This was not unexpected as the leukotoxin is a major virulence
      factor of the bacterium. The genes encoding the response regulators for the
      putative two-component regulatory systems were found to be expressed in more
      samples than the genes encoding the sensor proteins. The regulator proteins may
      be required in higher levels to regulate expression of target genes.

PMID- 16984403
TI  - Members of the Arabidopsis AtTPK/KCO family form homomeric vacuolar channels in
      planta.
AB  - The Arabidopsis thaliana K+ channel family of AtTPK/KCO proteins consists of six
      members including a 'single-pore' (Kir-type) and five 'tandem-pore' channels.
      AtTPK4 is currently the only ion channel of this family for which a function has
      been demonstrated in planta. The protein is located at the plasma membrane
      forming a voltage-independent K+ channel that is blocked by extracellular calcium
      ions. In contrast, AtTPK1 is a tonoplast-localized protein, that establishes a K+
      selective, voltage-independent ion channel activated by cytosolic calcium when
      expressed in a heterologous system, i.e. yeast. Here, we provide evidence that
      other AtTPK/KCO channel subunits, i.e. AtTPK2, AtTPK3, AtTPK5 and AtKCO3, are
      also targeted to the vacuolar membrane, opening the possibility that they
      interact at the target membrane to form heteromeric ion channels. However, when
      testing the cellular expression patterns of AtTPK/KCO genes we observed distinct
      expression domains that overlap in only a few tissues of the Arabidopsis plant,
      making it unlikely that different channel subunits interact to form heteromeric
      channels. This conclusion was substantiated by in planta expression of
      combinations of selected tonoplast AtTPK/KCO proteins. Fluorescence resonance
      energy transfer assays indicate that protein interaction occurs between identical
      channel subunits (most efficiently between AtTPK1 or AtKCO3) but not between
      different channel subunits. The finding could be confirmed by bimolecular
      fluorescence complementation assays. We conclude that tonoplast-located AtTPK/KCO
      subunits form homomeric ion channels in vivo.

PMID- 16984404
TI  - Regulation of cytoskeletal dynamics at the immune synapse: new stars join the
      actin troupe.
AB  - Reorganization of actin cytoskeletal dynamics plays a critical role in
      controlling T-lymphocyte activation and effector functions. Interaction of T-cell
      receptors (TCR) with appropriate major histocompatibility complex-peptide
      complexes on antigen-presenting cells results in the activation of signaling
      cascades, leading to the accumulation of F-actin at the cell-cell contact site.
      This event is required for the formation and stabilization of the immune synapse
      (IS), a cellular structure essential for the modulation of T-cell responses.
      Analysis of actin cytoskeletal dynamics following engagement of the TCR has
      largely focused on the Arp2/3 regulator, WASp, because of its early
      identification and its association with human disease. However, recent studies
      have shown equally important roles for several additional actin regulatory
      proteins. In this review, we turn the spotlight on the expanding cast of actin
      regulatory proteins, which co-ordinate actin dynamics at the IS.

PMID- 16984405
TI  - Ternary SNARE complexes are enriched in lipid rafts during mast cell exocytosis.
AB  - Lipid rafts are membrane microdomains rich in cholesterol and glycosphingolipids
      that have been implicated in the regulation of intracellular protein trafficking.
      During exocytosis, a class of proteins termed SNAREs mediate secretory granule
      plasma membrane fusion. To investigate the role of lipid rafts in secretory
      granule exocytosis, we examined the raft association of SNARE proteins and SNARE
      complexes in rat basophilic leukemia (RBL) mast cells. The SNARE protein SNAP-23
      co-localized with a lipid raft marker and was present in detergent-insoluble
      lipid raft microdomains in RBL cells. By contrast, only small amounts (<20%) of
      the plasma membrane SNARE syntaxin 4 or the granule-associated SNARE vesicle
      associated membrane protein (VAMP)-2 were present in these microdomains. Despite
      this, essentially all syntaxin 4 and most of VAMP-2 in these rafts were present
      in SNARE complexes containing SNAP-23, while essentially none of these complexes
      were present in nonraft membranes. Whereas SNAP-23 is membrane anchored by
      palmitoylation, the association of the transmembrane protein syntaxin 4 with
      lipid rafts was because of its binding to SNAP-23. After stimulating mast cells
      exocytosis, the amount of syntaxin 4 and VAMP-2 present in rafts increased
      twofold, and these proteins were now present in raft-associated phospho-SNAP
      23/syntaxin 4/VAMP-2 complexes, revealing differential association of SNARE
      fusion complexes during the process of regulated exocytosis.

PMID- 16984406
TI  - Retrovirus RNA trafficking: from chromatin to invasive genomes.
AB  - Full-length retroviral RNA has three well-established functions: it constitutes
      the genomic RNA that is packaged into virions and is transmitted to target cells
      by infection, it is the messenger RNA (mRNA) template for viral Gag and Pol
      protein synthesis and it serves as the pre-mRNA for the production of subgenomic
      spliced mRNAs that encode additional viral proteins such as Env. More recent work
      indicates that these full-length RNAs also play important roles in the assembly
      of virus particles, not only as a structural scaffold that facilitates viral core
      formation but also as a potential regulator of the assembly process itself. Here,
      we discuss how these assorted activities may be coupled with each other, paying
      particular attention to the importance of RNA trafficking and subcellular
      localization in the cytoplasm, possible points of regulation, and the role(s)
      played by cellular RNA-binding proteins.

PMID- 16984407
TI  - EGF-induced activation of the EGF receptor does not trigger mobilization of
      caveolae.
AB  - Caveolae-dependent endocytosis has recently been proposed in the uptake of EGF
      receptor (EGFR) at high concentrations of ligand. Consistently, upon incubation
      of HEp2 and HeLa cells with methyl-beta-cyclodextrin, we observed a small
      inhibitory effect on endocytosis of ligated EGFR in HEp2 cells. However,
      immunoelectron microscopy showed the same relative amount of bound EGF localizing
      to caveolae on incubation with high and low concentrations of EGF, not supporting
      rapid recruitment of EGFR to caveolae. Live-cell microscopy furthermore
      demonstrated that incubating HEp2 cells with high concentrations of EGF did not
      increase the mobility of caveolae. By RNA-interference-mediated knockdown of
      clathrin heavy chain in HEp2 and HeLa cells, we found that endocytosis of EGFR
      was efficiently inhibited both at high and low concentrations of EGF. Our results
      show that caveolae are not involved in endocytosis of EGF-bound EGFR to any
      significant degree and that high concentrations of EGF do not further mobilize
      caveolae.

PMID- 16984409
TI  - Functional genomics of Plasmodium falciparum through transposon-mediated
      mutagenesis.
AB  - Plasmodium falciparum is the causative agent for the most lethal form of human
      malaria, killing millions annually. Genetic analyses of P. falciparum have been
      relatively limited due to the lack of robust techniques to manipulate this
      parasite. Development of transfection technologies and whole genome analyses have
      helped in understanding the complex biology of this parasite. Even with this
      wealth of information functional genomics approaches are still very limited in P.
      falciparum due to the cumbersome and inefficient methods of genetic manipulation.
      This review focuses on a recently developed, highly efficient method for
      transposon-based mutagenesis and transgene expression in P. falciparum that will
      allow functional genomics studies to be performed proficiently on this deadly
      malaria parasite. By using a piggyBac-based transposition system, multiple random
      integrations have been obtained into the genome of the parasite. This technique
      could hence be employed to set up several biological screens in this lethal
      protozoan parasite that may lead to identification of novel drug targets and
      vaccine candidates.

PMID- 16984408
TI  - Nucleocytoplasmic shuttling and the biological activity of mouse survivin are
      regulated by an active nuclear export signal.
AB  - Survivin appears to function as a regulator of cell division and as an apoptosis
      inhibitor in many species. Here, we characterized the nucleocytoplasmic transport
      of mouse survivin(140), and its splice variants survivin(121) and survivin(40).
      We show that the dynamic intracellular localization of survivin(140) is mediated
      by a Crm1-dependent nuclear export signal (NES) present also in survivin(121),
      but absent in survivin(40). In contrast, neither survivin nor survivin splice
      variants contain an active nuclear import signal and seem to enter the nucleus by
      passive diffusion. The activity of the NES is required for survivin-mediated
      protection against cell death inducing stimuli and influences protein
      degradation. During mitosis, NES-deficient survivin variants fail to correctly
      localize to the mitotic machinery and promote proper cell division. In vivo and
      in vitro protein interaction assays show that survivin(140) and survivin(121) as
      well as their export-deficient mutants are able to form homo- as well as
      heterodimers. The trans-dominant negative phenotype observed upon expression of
      export-deficient survivin appears, therefore, to be mediated by the formation of
      inactive survivin heterodimers. The survivin-Crm1 axis is essential for the
      biological activities of murine survivin, and mouse models will allow
      investigating its functional implications during development and tumorigenesis.

PMID- 16984410
TI  - Getting infectious: formation and maturation of Plasmodium sporozoites in the
      Anopheles vector.
AB  - Research on Plasmodium sporozoite biology aims at understanding the developmental
      program steering the formation of mature infectious sporozoites - the
      transmission stage of the malaria parasite. The recent identification of genes
      that are vital for sporozoite egress from oocysts and subsequent targeting and
      transmigration of the mosquito salivary glands allows the identification of
      mosquito factors required for life cycle completion. Mature sporozoites appear to
      be equipped with the entire molecular repertoire for successful transmission and
      subsequent initiation of liver stage development. Innovative malaria intervention
      strategies that target the early, non-pathogenic phases of the life cycle will
      crucially depend on our insights into sporozoite biology and the underlying
      molecular mechanisms that lead the parasite from the mosquito midgut to the
      liver.

PMID- 16984411
TI  - Differential interactions of fimbriae and lipopolysaccharide from Porphyromonas
      gingivalis with the Toll-like receptor 2-centred pattern recognition apparatus.
AB  - The lipopolysaccharide (LPS) and fimbriae of Porphyromonas gingivalis play
      important roles in periodontal inflammation and pathogenesis. We investigated
      fimbriae and LPS from several P. gingivalis strains in terms of relative
      dependence on Toll-like receptor (TLR) signalling partners or accessory pattern
      recognition molecules mediating ligand transfer to TLRs, and determined induced
      assembly of receptor complexes in lipid rafts. Fimbriae could utilize TLR1 or
      TLR6 for cooperative TLR2-dependent activation of transfected cell lines, in
      contrast to LPS and a mutant version of fimbriae which displayed preference for
      TLR1. Whether used to activate human cell lines or mouse macrophages, fimbriae
      exhibited strong dependence on membrane-expressed CD14 (mCD14), which could not
      be substituted for by soluble CD14 (sCD14). In contrast, sCD14 efficiently
      substituted for mCD14 in LPS-induced cellular activation. LPS-binding protein was
      more important for LPS- than for fimbria-induced cell activation, whereas the
      converse was true for CD11b/CD18. Cell activation by LPS or fimbriae required
      lipid raft function and formation of heterotypic receptor complexes (TLR1
      2/CD14/CD11b/CD18), although wild-type fimbriae additionally recruited TLR6. In
      summary, TLR2 activation by P. gingivalis LPS or fimbriae involves differential
      dependence on accessory signalling or ligand-binding receptors, which may
      differentially influence innate immune responses.

PMID- 16984412
TI  - Bacterial flagellin inhibits T cell receptor-mediated activation of T cells by
      inducing suppressor of cytokine signalling-1 (SOCS-1).
AB  - Flagellin, the structural component of bacterial flagella, is secreted by
      pathogenic and commensal bacteria, and is recognized by Toll-like receptor (TLR)
      5. Flagellin is a common bacterial antigen present on most motile bacteria and is
      speculated to contribute to the activation of CD4+ T cells in the intestine.
      However, molecular mechanisms by which flagellin regulate T cell activation
      remains to be determined. Using Jurkat T cells or human primary T cell, we showed
      that flagellin stimulation induced tyrosine phosphorylation of TLR5 and
      activation of both mitogen-activated protein kinases and nuclear factor kappaB.
      In addition, stimulation by flagellin did not induce nuclear factor of activated
      T cells (NFAT) activation, while stimulation via the T cell receptor (TCR) leads
      to activation of NFAT. However, TCR-mediated NFAT activation and tyrosine
      phosphorylation of zeta-associated protein 70 (Zap-70) were inhibited in cells
      pre-stimulated by flagellin. Furthermore, flagellin stimulation induced
      suppressor of cytokine signalling-1 (SOCS-1), which formed a complex with Zap-70
      after stimulation via TCR, and inhibition of SOCS-1 expression by SOCS-1-specific
      small interfering RNA reinstated TCR-mediated activation of NFAT in cells pre
      stimulated with flagellin. These results collectively indicate that bacterial
      flagellin inhibits TCR-mediated activation of T cells by inducing SOCS-1.

PMID- 16984413
TI  - Beta 1, 3-glucan recognition protein from the mosquito, Armigeres subalbatus, is
      involved in the recognition of distinct types of bacteria in innate immune
      responses.
AB  - The activation of an immune response to invading microorganisms generally
      requires recognition by pattern recognition receptors. Beta 1, 3-glucan
      recognition proteins (GRPs) have specific affinity for beta 1, 3-glucan, a
      component on the surface of fungi and bacteria. In this study, we show that GRP
      from Armigeres subalbatus mosquitoes (AsGRP) is able to bind different bacterial
      species, and that this binding varies from species to species and is independent
      of Gram type. AsGRP knockdown with double-stranded RNA increases the mortality of
      mosquitoes to those bacteria that strongly bind AsGRP, but not to bacteria that
      do not detectably bind AsGRP. This increase in susceptibility is partially
      evidenced by decreased melanization in Salmonella typhimurium. Furthermore, AsGRP
      expression is differentially affected by the presence of different species of
      bacteria. These results demonstrate that AsGRP is selective in its affinity to
      different bacteria and; therefore, plays a role in the antibacterial immune
      response of mosquitoes.

PMID- 16984414
TI  - Pore-forming Staphylococcus aureus alpha-toxin triggers epidermal growth factor
      receptor-dependent proliferation.
AB  - Staphylococcal alpha-toxin is an archetypal killer protein that homo-oligomerizes
      in target cells to create small transmembrane pores. The membrane-perforating
      beta-barrel motif is a conserved attack element of cytolysins of Gram-positive
      and Gram-negative bacteria. Following the recognition that nucleated cells can
      survive membrane permeabilization, a profile of abundant transcripts was obtained
      in transiently perforated keratinocytes. Several immediate early genes were found
      to be upregulated, reminiscent of the cellular response to growth factors. Cell
      cycle analyses revealed doubling of S + G2/M phase cells 26 h post toxin
      treatment. Determination of cell counts uncovered that after an initial drop,
      numbers increased to exceed the controls after 2 days. A non-lytic alpha-toxin
      mutant remained without effect. The alpha-toxin pore is too small to allow egress
      of cytosolic growth factors, and evidence was instead obtained for growth
      signalling via the epidermal growth factor receptor (EGFR). Inhibition of the
      EGFR or of EGFR-proligand-processing blocked the mitogenic effect of alpha-toxin.
      Western blots with phospho-specific antibodies revealed activation of the EGFR,
      and of the adapter protein Shc. Immediate early response and proliferation upon
      transient plasma membrane pore formation by bacterial toxins may represent a
      novel facet of the complex interaction between pathogen and host.

PMID- 16984415
TI  - Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium
      signalling.
AB  - The opportunistic pathogen Pseudomonas aeruginosa utilizes a cell density
      dependent signalling phenomenon known as quorum sensing (QS) to regulate several
      virulence factors needed for infection. Acylated homoserine lactones, or
      autoinducers, are the primary signal molecules that mediate QS in P. aeruginosa.
      The autoinducer N-3O-dodecanoyl-homoserine lactone (3O-C12) exerts effects on
      mammalian cells, including upregulation of pro-inflammatory mediators and
      induction of apoptosis. However, the mechanism(s) by which 3O-C12 affects
      mammalian cell responses is unknown. Here we report that 3O-C12 induces apoptosis
      and modulates the expression of immune mediators in murine fibroblasts and human
      vascular endothelial cells (HUVEC). The effects of 3O-C12 were accompanied by
      increases in cytosolic calcium levels that were mobilized from intracellular
      stores in the endoplasmic reticulum (ER). Calcium release was blocked by an
      inhibitor of phospholipase C, suggesting that release occurred through inositol
      triphosphate (IP3) receptors in the ER. Apoptosis, but not immunodulatory gene
      activation, was blocked when 3O-C12-exposed cells were co-incubated with
      inhibitors of calcium signalling. This study indicates that 3O-C12 can activate
      at least two independent signal transduction pathways in mammalian cells, one
      that involves increases in intracellular calcium levels and leads to apoptosis,
      and a second pathway that results in modulation of the inflammatory response.

PMID- 16984416
TI  - Induction of dendritic cell migration upon Toxoplasma gondii infection
      potentiates parasite dissemination.
AB  - The processes leading to systemic dissemination of the obligate intracellular
      parasite Toxoplasma gondii remain unelucidated. In vitro studies on human and
      murine dendritic cells (DC) revealed that active invasion of DC by Toxoplasma
      induces a state of hypermotility in DC, enabling transmigration of infected DC
      across endothelial cell monolayers in the absence of chemotactic stimuli.
      Infected DC exhibited upregulation of maturation markers and co-stimulatory
      molecules. While modulation of cell adhesion molecules CD11/CD18 was similar for
      Toxoplasma-infected DC and lipopolysaccharide (LPS)-matured DC, Toxoplasma
      infected DC did not exhibit upregulation of CD54/ICAM-1. Induction of host cell
      migration in vitro required live intracellular parasite(s) and was inhibited by
      uncoupling the Gi-protein signalling pathway with pertussis toxin, but did not
      depend on CCR5, CCR7 or Toll/interleukin-1 receptor signalling. When migration of
      Toxoplasma-infected DC was compared with migration of LPS-stimulated DC in vivo,
      similar or higher numbers of Toxoplasma-infected DC reached the mesenteric lymph
      nodes and spleen respectively. Adoptive transfer of Toxoplasma-infected DC
      resulted in more rapid dissemination of parasites to distant organs and in
      exacerbation of infection compared with inoculation with free parasites.
      Altogether, these findings show that Toxoplasma is able to subvert the regulation
      of host cell motility and likely exploits the host's natural pathways of cellular
      migration for parasite dissemination.

PMID- 16984417
TI  - The use of bacterial minicells to transfer plasmid DNA to eukaryotic cells.
AB  - The delivery of DNA to mammalian cells is of critical importance to the
      development of genetic vaccines, gene replacement therapies and gene silencing.
      For these applications, targeting, effective DNA transfer and vector safety are
      the major roadblocks in furthering development. In this report, we present a
      novel DNA delivery vehicle that makes use of protoplasted, achromosomal bacterial
      minicells. Transfer of plasmid DNA as measured by green fluorescent protein
      expression was found to occur in as high as 25% of cultured Cos-7 cells when a
      novel chimeric protein containing the D2-D5 region of invasin was expressed and
      displayed on the surface of protoplasted minicells. Based on endoplasmic
      reticulum stress and other responses, protoplasted minicells were non-toxic to
      recipient eukaryotic cells as a consequence of the transfection process. Taken
      together, these results suggest that bacterial minicells may represent a novel
      and promising gene delivery vehicle.

PMID- 16984418
TI  - Inactivation of Bacillus anthracis spores in murine primary macrophages.
AB  - The current model for pathogenesis of inhalation anthrax indicates that the
      uptake and fate of Bacillus anthracis spores in alveolar macrophages are critical
      to the infection process. We have employed primary macrophages, which are more
      efficient for spore uptake than the macrophage-like cell line RAW264.7, to
      investigate spore uptake and survival. We found that at a multiplicity of
      infection (moi) of 5, greater than 80% of the spores of the Sterne strain
      containing only the pXO1 plasmid were internalized within 1 h. Within 4 h post
      infection, viability of internalized Sterne spores decreased to approximately
      40%. Intracellular vegetative bacteria represented less than 1% of the total
      spore inoculum throughout the course of infection suggesting effective killing of
      germinated spores and/or vegetative bacteria. The Sterne spores trafficked
      quickly to phagolysosomes as indicated by colocalization with lysosome-associated
      membrane protein 1 (LAMP1). Expression of a dominant-negative Rab7 that blocked
      lysosome fusion enhanced Sterne spore survival. Addition of d-alanine to the
      infection resulted in 75% inhibition of spore germination and increased survival
      of internalized spores of the Sterne strain and a pathogenic strain containing
      both the pXO1 and pXO2 plasmids. Inhibition was reversed by the addition of l
      alanine, which resumed spore germination and subsequent spore killing. Our data
      indicate that B. anthracis spores germinate in and are subsequently killed by
      primary macrophages.

PMID- 16984419
TI  - NF-kappaB and inhibitor of apoptosis proteins are required for apoptosis
      resistance of epithelial cells persistently infected with Chlamydophila
      pneumoniae.
AB  - Infection with Chlamydophila pneumoniae (Cpn) renders host cells resistant to
      apoptosis induced by a variety of stimuli. While modulation of apoptosis has been
      extensively studied in cells acutely infected with Cpn, very little is known on
      how persistent chlamydial infection influences host cell survival. Here we show
      that epithelial cells persistently infected with Cpn resist apoptosis induced
      with TNFalpha or staurosporine. Cpn induced the activation of nuclear factor
      kappa B (NF-kappaB) and inhibition of NF-kappaB with a chemical inhibitor or by
      silencing expression of the p65 subunit sensitized infected cells for apoptosis
      induction by staurosporine or TNFalpha. Persistent infection resulted in the
      upregulation of the NF-kappaB regulated inhibitor of apoptosis protein 2 (cIAP-2)
      but not inhibitor of apoptosis protein 1 (cIAP-1). Interestingly, silencing of
      either cIAP-1 or cIAP-2 sensitized infected cells, suggesting that IAPs play an
      important role in the apoptosis resistance of persistently infected cells.

PMID- 16984420
TI  - Alpha-toxin interferes with integrin-mediated adhesion and internalization of
      Staphylococcus aureus by epithelial cells.
AB  - Staphylococcus aureus is an important human and animal pathogen. During
      infection, this bacterium is able to attach to and enter host cells by using its
      cell surface-associated factors to bind to the host's extracellular matrix (ECM)
      proteins. In this study, we determined that a protein exported by S. aureus,
      alpha-toxin, can interfere with the integrin-mediated adhesion and
      internalization of S. aureus by human lung epithelial cells (A549). The
      downregulation of alpha-toxin production significantly increased bacterial
      adhesion and invasion into the epithelial cells. In contrast, bacterial adhesion
      and invasion was inhibited by both overproduction of alpha-toxin and the addition
      of alpha-toxin to the culture medium. Moreover, our results showed that the
      quantitative effects on invasion closely parallel those of adherence. This
      suggests that the effect on invasion is probably secondary to, and a consequence
      of, the reduced adherence caused by alpha-toxin exposure. Specifically, we
      demonstrated that alpha-toxin interacts with the hosts' ECM protein's receptor,
      beta1-integrin, which indicates that beta1-integrin may be a potential receptor
      of alpha-toxin on epithelial cells. Taken together, our results indicate that
      exported alpha-toxin inhibits the adhesion and internalization of S. aureus by
      interfering with integrin-mediated pathogen-host cell interactions.

PMID- 16984422
TI  - Abrogation of the fibrotic effect of transforming growth factor-beta in dermal
      wound healing.
AB  - The growth factor, transforming growth factor-beta1, which under normal
      circumstances promotes wound healing by stimulating local fibroblasts to produce
      collagen and other extracellular matrix proteins, has also been implicated as the
      primary causative agent of fibrosis. Because transforming growth factor-beta1 is
      capable of stimulating its own production by fibroblasts, its normally beneficial
      effects may become amplified to the point where excess extracellular matrix
      accumulation occurs, thereby causing abnormal scarring. Therefore, strategies
      that block or counter the effects of transforming growth factor-beta1 may be
      useful in preventing or decreasing fibrosis. One such strategy is the use of
      glucocorticoid steroids such as dexamethasone, which normally have the opposite
      effect of transforming growth factor-beta1, namely the impairment of wound
      healing. When used in conjunction with transforming growth factor-beta1,
      glucocorticoid steroids may normalize the effect of transforming growth factor
      beta1 on collagen synthesis, thereby reducing excessive collagen deposition and
      fibrosis.

PMID- 16984423
TI  - Long-term results of aggressive management of diabetic foot ulcers suggest
      significant cost effectiveness.
AB  - This study was undertaken to examine the hypothesis that the initial high limb
      salvage rate in patients with diabetes who are treated aggressively with a
      multidisciplinary approach to management of severe, chronic lower extremity
      wounds is durable and cost effective. In 1991 a cohort of 41 patients with
      diabetes with severe, chronic foot wounds was selected by a neutral, blinded
      observer who had no knowledge of the outcomes from a group of 101 consecutive
      such patients who had been treated at our wound center from 1983 to 1990. All had
      limb-threatening lesions, scoring 3 to 4 on the Wagner scale, were treated for at
      least 7 days with adjunctive hyperbaric oxygen, and had photographic and medical
      documentation. Durability of wound repair was examined in 1991 and 1993. Initial
      limb salvage was 85%. Mean hospital charges were $31,264, including average
      hyperbaric charges of $15,000. At the initial review, 28 of the patients with
      previously salvaged limbs (80%) were contacted. Of the 28 patients, 27 remained
      intact (96%). The mean durability of repair was 2.6 years. At the second review,
      the mean duration of repair in surviving patients was 4.6 years with no further
      expenditures relative to the salvaged limb. In patients who died, average
      durability was 3.4 years, also without additional expenditure referable to the
      salvaged extremity. Most complex lower extremity lesions were healed by a
      comprehensive wound care program which included vascular surgery and hyperbaric
      oxygen. The results were durable, and the treatment was cost effective and humane
      compared with early amputation.

PMID- 16984424
TI  - Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation.
AB  - Diabetic wounds are characterized by a prolonged wound healing process with
      insufficient formation of granulation tissue. Systemic hyperbaric oxygen therapy
      has been observed to improve the healing of these wounds. However, the
      mechanism(s) responsible for these findings are not yet fully elucidated. In the
      present study we have studied the in vitro effects of hyperbaric oxygen on
      proliferation of human fibroblasts from normal skin and from chronic foot ulcers
      in non-insulin-dependent diabetics. A 1-hour exposure to hyperbaric oxygen at
      oxygen pressures between 106 and 300 kPa (795 to 2250 mm Hg) increased the
      proliferation in both diabetic and normal fibroblasts. The stimulatory effect was
      dose-dependent, with a peak increase in cell proliferation at 250 kPa and 200 kPa
      for normal and diabetic cells, respectively. The effects were not due to
      hydrostatic pressure per se. These results suggest that hyperbaric oxygen could
      stimulate fibroblast activity in the diabetic wound, a finding that could explain
      the enhanced formation of granulation tissue seen clinically in wounds treated
      with hyperbaric oxygen. We also speculate that mechanisms other than just
      increased oxygen availability may be responsible for our findings.

PMID- 16984425
TI  - In vitro analysis of fetal fibroblast collagenolytic activity.
AB  - Tissue repair in the rabbit fetus is remarkably rapid and occurs without
      significant inflammation or excessive collagen deposition. The objective of this
      study was to compare the ability of rabbit fetal and adult fibroblasts to express
      the matrix metalloproteinases which are thought to be critical to scar tissue
      remodeling. In vitro, both fetal and adult rabbit fibroblasts express
      procollagenase messenger RNA in a constitutive manner. Mechanical disruption of
      fetal fibroblast monolayers caused a twofold increase in procollagenase mRNA. In
      contrast, the adult rabbit fibroblast procollagenase mRNA remained unchanged. The
      mRNA data correlated well with enzyme protein levels. Quantitation by
      immunoprecipitation showed a 2.3-fold increase in fetal fibroblast procollagenase
      protein after mechanical injury, whereas the level in adult rabbit fibroblasts
      remained unchanged. However, it was noted that the constitutive levels of
      procollagenase mRNA and protein were higher in adult fibroblasts. Analysis of
      enzyme activity, by means of a fluorogenic substrate, showed that adult
      fibroblasts had 2.2 times more collagenase activity compared with fetal cells.
      After mechanical injury, the fetal fibroblast collagenase activity increased 1.3
      fold compared with 1.7-fold in the adult fibroblasts. In contrast, fetal
      fibroblast gelatinase activity was 1.25 times greater than in adult cells and
      increased 1.4-fold after mechanical injury, whereas the adult profile remained
      unchanged. Immunolocalization studies indicated that 1 hour after mechanical
      injury, procollagenase was produced primarily by fibroblasts along the mechanical
      injury ridge. By 4 hours after injury, the ridge cells began to migrate out into
      the open area and procollagenase was noted in adjacent cells of both adult and
      fetal origin. By 12 and 18 hours, all cells throughout the monolayer were
      expressing procollagenase. These findings show that in vitro fetal fibroblasts
      actually had lower levels of procollagenase, but higher levels of gelatinase
      compared with adult fibroblasts. The increased gelatinase expression may explain
      why fetal wounds do not have excessive collagen accumulation and heal without a
      visible scar.

PMID- 16984426
TI  - In vitro studies on the antioxidant and growth stimulatory activities of a
      polyphenolic extract from Cudrania cochinchinensis used in the treatment of
      wounds in Vietnam.
AB  - The leaves of Cudrania cochinchinensis, a Vietnamese folk remedy, have been
      suggested as a beneficial agent for wound healing. Animal studies and clinical
      observations in Vietnam have shown positive wound healing activity. We studied
      the effects of a polyphenolic extract from the plant on the proliferation of
      cells in culture and their response to oxidative damage by hydrogen peroxide.
      Fibroblasts were incubated with different concentrations of the extract in 0.4%
      fetal calf serum, and proliferation was monitored by a colorimetric assay. Cell
      damage was induced by exposure to hydrogen peroxide 7 x 10(-5) mol/L for 3 hours.
      The same colorimetric assay was used to assess cell damage and the protective
      effect of the extract against oxidative damage. The extract at low concentrations
      (0.1 to 5 microg/ml) had a stimulatory effect on fibroblast growth. The effect
      was significant by 7 days after the addition of the extract and was strongest at
      a concentration of 1 microg/ml of extract (p< or = 0.01). The extract at
      concentrations of 5 or 50 microg/ml protected fibroblasts and endothelial cells
      against hydrogen peroxide-induced damage. Pretreatment with the extract or
      exposure to extract simultaneously with hydrogen peroxide gave only partial
      protection against oxidative damage, whereas a combination of the two treatments
      gave complete protection (p< or = 0.005). Stimulation of fibroblast proliferation
      and protection of cells against destruction by inflammatory mediators may be ways
      in which the polyphenolic substances from the plant, Cudrania cochinchinensis,
      contribute to wound healing.

PMID- 16984427
TI  - Growth hormone but not insulin-like growth factor-I improves wound strength in
      pigs.
AB  - Systemic growth hormone and locally administered insulin-like growth factor-I
      have been shown in a number of studies to improve the breaking strength of
      incisional wounds, especially in compromised animals. The objective of the
      present study was to compare these two agents when administered subcutaneously
      distant from an incisional wound site in pigs, as well as to examine effects of a
      combination growth hormone/insulin-like growth factor treatment. Growth hormone
      was shown to increase wound breaking strength in two experiments, whereas insulin
      like growth factor-I or a more potent analog had no effect. Moreover, breaking
      strength was only minimally improved above the vehicle groups by the combination
      of growth hormone and insulin-like growth factor-I. These effects could not be
      explained by changes in plasma insulin-like growth factor-I concentrations which
      were highest in the combination groups, nor by plasma insulin-like growth factor
      binding protein-3 which was raised equally whenever growth hormone was
      administered. We conclude that systemic growth hormone but not insulin-like
      growth factor-I improves wound strength in normal pigs, whereas insulin-like
      growth factor-I reduces the magnitude of the growth hormone effect by an unknown
      mechanism.

PMID- 16984428
TI  - Acceleration of dermal tissue repair by angiotensin II.
AB  - Angiotensin II is a naturally occurring peptide which has been shown to possess
      angiogenic properties. In the studies reported here, angiotensin II was shown to
      increase the proliferation of cultured bovine aortic arch endothelial cells in a
      concentration-dependent manner. Acute administration of angiotensin II in Hydron
      accelerated the repair of dermal injuries in a full-thickness excisional rat
      model. Additional studies were done to determine the best vehicle for delivery of
      angiotensin II to a dermal injury. Several vehicles, including 10% low-viscosity
      carboxymethyl cellulose, 4% medium-viscosity carboxymethyl cellulose, and 3% high
      viscosity carboxymethyl cellulose, were found to be effective in this regard.
      Daily administration of angiotensin II for days 0 to 4 after injury (day 0 being
      the time of surgery) was determined to provide the optimal dosage for
      acceleration of wound repair by angiotensin II. In addition, dose-response
      studies indicated that angiotensin II accelerated wound repair in a dose
      dependent fashion with 0.03 and 0.01 microg/rat/day of angiotensin II
      administered on days 0 to 4 being the minimally effective and no-effect doses,
      respectively. Administration of 100 microg/day of angiotensin II in 10%
      carboxymethyl cellulose for 5 days after injury to animals with impaired healing
      (steroid- and adriamycin-treated rats and diabetic mice) was also found to
      accelerate the rate of repair. In conclusion, angiotensin II accelerated the
      closure of full-thickness skin injuries in a dose-dependent manner in normal and
      impaired animal models.

PMID- 16984429
TI  - Single local instillation of nonviable Staphylococcus aureus or its peptidoglycan
      ameliorates glucocorticoid-induced impaired wound healing.
AB  - An excess in glucocorticoid steroids, either from endogenous or exogenous
      sources, has been shown to inhibit wound repair. Key to this impairment is a
      diminution of the inflammatory response to wounding, fibroplasia, capillary
      formation, reparative tissue collagen accumulation, and wound breaking strength.
      Because a single local application at operation of nonviable Staphylococcus
      aureus or its peptidoglycan increases all of these processes in normal rats, we
      hypothesized that nonviable S. aureus and S. aureus peptidoglycan would each
      ameliorate glucocorticoid-induced impaired healing. Sprague-Dawley male rats
      aseptically received two 7 cm paravertebral skin incisions and underwent
      subcutaneous implantation of polyvinyl alcohol sponges. Two glucocorticoids were
      used: hydrocortisone, 8 mg intramuscularly, daily beginning 1 day before
      operation and continuing during the postoperative period; or a single dose of a
      long-acting preparation of methylprednisolone, 6 or 8 mg intramuscularly, on the
      day before operation. Controls received intramuscular injections of saline
      solution at the same respective times. At the time of the operation, one incision
      and the polyvinyl alcohol sponges on one side of the animal were instilled with
      saline solution while the incision and sponges on the opposite side were
      instilled with nonviable S. aureus (hydrocortisone study) or S. aureus
      peptidoglycan (two methylprednisolone studies). The data showed that, at
      postoperative day 7, the single local application at wounding of nonviable S.
      aureus or S. aureus peptidoglycan increased wound breaking strength in the
      control rats by factors of 1.6 in the hydrocortisone experiment and 1.4 and 1.6
      in the methylprednisolone studies. These treatments prevented (in hydrocortisone
      treated rats) or mitigated (in methylprednisolone-treated rats) the
      glucocorticoid-induced decrease in wound breaking strength. In addition, these
      treatments prevented the glucocorticoid-induced decreases in the inflammatory
      (largely mononuclear cells) response to wounding and in the accumulation within
      the polyvinyl alcohol sponge of reparative tissue fibroblasts, capillaries, and
      collagen.

PMID- 16984430
TI  - Effective management of microbial contamination in cultured skin substitutes
      after grafting to athymic mice.
AB  - Cultured skin substitutes have become therapeutic alternatives for treatment of
      acute and chronic skin wounds, but all models of these substitutes are avascular
      and susceptible to microbial destruction during vascularization. To develop a
      practical management protocol for increased survival of skin substitutes,
      experimental wounds were contaminated with Pseudomonas aeruginosa and treated
      with a formulation of noncytotoxic antimicrobial agents (polymyxin B, neomycin,
      ciprofloxacin, mupirocin, amphotericin B) in a nutrient medium (vehicle).
      Cultured skin substitutes consisting of human keratinocytes and fibroblasts
      attached to collagen-glycosaminoglycan sponges were grafted to 2 x 2 cm full
      thickness wounds on athymic mice that were contaminated with the strain SBI-N of
      P. aeruginosa at 1 x 10(4), 1 x 10(5), and 1 x 10(6) organisms/wound.
      Experimental wounds were irrigated with 1 ml/day topical antimicrobial solution
      for 10 days, and controls received vehicle only. Two, three, and four weeks after
      grafting, wounds were traced and swabbed for microbial culture and areas were
      measured with planimetry. At 4 weeks, biopsy samples were scored histochemically
      for immunoreactivity to HLA antigens. Data analysis by chi-square, analysis of
      variance, and Tukey's test shows that treatment of contaminated wounds with
      noncytotoxic topical antimicrobials is associated with an increased area of
      healed wounds, positive detection of HLA antigens, and negative cultures for P.
      aeruginosa. These results show that microbial contamination of cultured skin
      substitutes on full-thickness wounds may be managed effectively during graft
      vascularization. However, this formulation of antimicrobial agents is not
      currently approved for human use and is investigational only. Effective
      management of microbial contamination suggests that clinical efficacy of
      avascular tissue analogs may be increased by local application of noncytotoxic
      antimicrobial agents.

PMID- 16984431
TI  - Mouse models to study wound closure and topical treatment of infected wounds in
      healing-impaired and normal healing hosts.
AB  - Full-thickness wounds were made on the backs of wound healing-impaired diabetic
      mice and their normally healing litter mates. The wounds were then inoculated
      with 10(4) colony-forming units of Pseudomonas aeruginosa. In both cases, the
      inoculum increased rapidly to between 10(9) and 10(10) colony-forming units/wound
      area. The infection caused a significant decrease in wound closure in the
      normally healing mice. In the wound healing-impaired diabetic mice, infection
      increased the size of the wound area over 100% by day 21. The wound became filled
      with inflammatory cells and serous fluid, and the mice lost significant amounts
      of weight, an additional sign of severe, ongoing infection. Early antimicrobial
      treatment of infected wounds in diabetic mice (1 hour after wounding and
      microbial inoculation) reversed the increase in wound size area, improved wound
      closure, and reduced to a significant degree the weight loss observed in
      untreated control mice. Delay in treatment for as little as 8 hours significantly
      reduces the efficacy of antimicrobial treatment. These models can be used to
      study the effects of infection as well as to determine the efficacy of topical
      antimicrobial and/or wound healing-enhancing substances on these wounds in both
      normally healing and healing-impaired hosts.

PMID- 16984434
TI  - Strategies for cell engineering in tissue repair.
AB  - Cellular and tissue engineering are new areas of research, currently attracting
      considerable interest because of the remarkable potential they have for clinical
      application. Some claims have indeed been dramatic, including the possibility of
      growing complete, artificial organs, such as the liver. However, amid such long
      term aspirations there is the very real possibility that small tissues
      (artificial grafts) may be fabricated in the near future for use in
      reconstructive surgery. Logically, we should focus on how it is possible to
      produce modest, engineered tissues for tissue repair. It is evident that
      strategies to date either depend on innate information within implanted cells, to
      reform the target tissue or aim to provide appropriate environmental cues or
      guidance to direct cell behavior. It is argued here that present knowledge of
      tissue repair biology points us toward the latter approach, providing external
      cues which will direct how cells should organize the new tissue. This will be
      particularly true where we need to reproduce microscopic and ultrastructural
      features of the original tissue architecture. A number of such cues have been
      identified, and methods are already available, including substrate chemistry,
      substrate contact guidance, mechanical loading, and biochemical mediators to
      provide these cues. Examples of these are already being used with some success to
      control the formation of tissue structures.

PMID- 16984435
TI  - Tissue expression of transforming growth factor-beta1 and transforming growth
      factor-alpha during wound healing in human skin explants.
AB  - In the dynamic and complex process of wound healing, locally produced growth
      factors are important mediators, although their actual roles have not been fully
      established. In the present study, the presence of transforming growth factor
      beta1 and -alpha during the re-epithelialization of full-thickness wounds was
      investigated in an in vitro model of wound healing in human skin. The amounts of
      transforming growth factor-beta1 and -alpha secreted from the wound area were
      measured with enzyme immunoassays, and immunohistochemistry was used to study the
      localization of these two growth factors in the healing wound. The wounds were
      followed until they were completely re-epithelialized. The results showed a
      continuous increase in secreted transforming growth factor-beta1 throughout the
      re-epithelialization phase of healing followed by a decrease after its
      completion. The keratinocytes migrating out from the wound edges showed intense
      staining for transforming growth factor-beta1 which declined to the level of the
      surrounding epidermis after the wound was covered by a new epidermis. After the
      skin was wounded, a decrease both in secreted transforming growth factor-alpha
      and in immunostaining for this growth factor was apparent. Even though a minor
      increase in the immunoreactivity for transforming growth factor-alpha occurred
      after the completion of re-epithelialization, no increase in secreted
      transforming growth factor-alpha could be detected by enzyme immunoassay. These
      data suggest that keratinocytes modulate their expression of transforming growth
      factor-beta1 and -alpha during the wound healing process in human skin and that
      these changes may be controlled in part by autocrine pathways.

PMID- 16984436
TI  - Expression of endogenous transforming growth factor-beta and its type I and type
      II receptors in rat burn wounds.
AB  - Transforming growth factor-beta is a potent regulator of numerous processes in
      wound healing. These biological activities require the interaction of the growth
      factor with two classes of cell surface receptors, namely the type I and type II
      receptors. To understand the role of transforming growth factor-beta in burn
      wound healing, we undertook a study to localize this growth factor and its cell
      surface receptors within dermal burn wounds. Partial-thickness burn injuries were
      made on the backs of Wistar rats. At 1, 3, 5, 7, 10, 15, and 20 days after
      burning, samples of wounded and control skin were removed for the isolation of
      total RNA and immunohistochemistry. Thermal injury induced the expression of mRNA
      for transforming growth factor-beta and both type I and type II receptors. The
      expression of transforming growth factor-beta peaked 5 to 7 days after injury,
      then gradually declined. Of note, the expression of the transforming growth
      factor-beta receptors returned to normal before the expression of the growth
      factor. Immunohistochemical analysis showed that transforming growth factor-beta
      protein levels paralleled mRNA expression, and the protein was primarily
      localized to the migrating epidermal cells and dermal fibroblasts. The
      differences between the expression of transforming growth factor-beta and its
      receptors in the later stages of healing thermal injuries suggests the presence
      of a well-controlled mechanism to limit the effect of the growth factor on repair
      cells.

PMID- 16984437
TI  - Cellular distribution of 5-lipoxygenase and leukotriene receptors in postsurgical
      peritoneal wound repair.
AB  - Products of the eicosanoid pathways, namely prostaglandins and leukotrienes, are
      known to play a key role in inflammatory and immune responses, as well as other
      wound cellular activities of wounded tissue. The objective of this study was to
      determine whether surgically induced intraperitoneal and incisional wounds in the
      rat express 5-lipoxygenase and contain binding sites for leukotrienes and whether
      their levels change during the course of healing. With the use of a specific
      monoclonal antibody generated against 5-lipoxygenase, the enzyme was
      immunohistochemically localized in various wound cells during postsurgical days 2
      to 35. The inflammatory cells within the wound were the major cell types
      containing 5-lipoxygenase immunoreactive protein, followed by fibroblasts in the
      incisional and peritoneal fibrous adhesions, striated muscle, and the
      vasculature. The greatest level of immunostaining was observed during the first 2
      weeks after surgery, which decreased to near unwounded levels by day 35. Light
      microscope autoradiographic binding studies using (3)H-leukotrienes indicated
      that the peritoneal/incisional wounds and unwounded tissues contain specific (3)H
      leukotriene C(4) and (3)H-leukotriene D(4) but not (3)H-leukotriene B(4) binding
      sites. Quantitative grain analysis (net grain density/100 microm(2)),
      representing specific (3)H-leukotriene C(4) and (3)H-leukotriene D(4) binding
      sites calculated for different cell types in the wound and unwounded regions
      showed that (3)H-leukotriene C(4) binding was highest over the striated muscle
      proximal to the injury and incisional and peritoneal granulation tissue
      fibroblasts. The net grain density over these cells increased by 3-, 2.5-, and 2
      fold by day 14, respectively, and declined to the control values by day 21 after
      injury (p < 0.05). The pattern of (3)H-leukotriene D(4) binding was similar to
      that observed for (3)H-leukotriene C(4), but with a lower density. The grain
      density for (3)H-leukotriene C(4) and (3)H-leukotriene D(4) in arteriolar
      endothelial and smooth muscle cells remained unchanged. These data suggest that
      the products of the lipoxygenase pathway through the presence of their specific
      receptors may play an important role in peritoneal wound repair and adhesion
      formation.

PMID- 16984438
TI  - Ultrastructural analysis of fetal rabbit wounds.
AB  - Fetal wound healing proceeds rapidly with minimal inflammation and fibroplasia
      and little or no scar formation. These observations have led to the hypothesis
      that fetal wound healing more closely resembles regeneration rather than adult
      wound repair. To test this hypothesis, this study used ultrastructural analysis
      of fetal and adult fibroblasts and collagen to gain greater insight into
      differences in the healing processes. Full-thickness, primarily closed linear
      incisions were created dorsally on 24-day gestational age fetal rabbits (n = 9).
      The fetuses were killed 5 days later, and the wounds were excised and evaluated
      with transmission electron microscopy. Similarly, uninjured fetal skin of the
      same gestational age was obtained and analyzed. Adult rabbit dermal wounds were
      analyzed after 8 days of healing. Resting adult dermal fibroblasts had features
      of quiescent, inactive cells, whereas adult wound fibroblasts were highly active
      and filled with secretory vesicles. In contrast, both fetal normal dermal and
      wound fibroblasts appeared highly active and contained numerous secretory
      vesicles. In the adult wound, collagen fibril diameter was only 45% of the
      diameter of normal dermal collagen. However, fetal wound collagen fibrils were
      basically the same as normal dermal collagen, having a diameter that was 82% of
      the size of dermal collagen. These observations suggest that fetal wound
      fibroblasts do not require activation from an inactivated state and that fetal
      wound collagen deposition undergoes more rapid organization and maturation. These
      findings have significance in extending our understanding of the rapidity and
      functional superiority of fetal wound healing compared with adult wound healing.

PMID- 16984440
TI  - Proteolytic activity in human burn wounds.
AB  - Wound healing is the result of a dynamic balance between synthetic and
      degradative processes. After a burn, proteolytic activity increases at the wound
      site. Excised burn wounds and donor skin were examined from 20 pediatric burn
      patients, to determine which of two classes of neutral proteinases, serine or
      metalloproteinases, accounts for the majority of this proteolytic activity in
      these tissues; to examine messenger RNA expression of three of the principal
      enzymes and inhibitors of this class; and to measure enzymatic activity of two of
      these metalloproteinases. The majority of the increased proteolysis was due to
      metalloproteinases. By polymerase chain reaction assays, messenger RNAs for
      matrix metalloproteinase-1, -3, and -9 were strongly expressed in burn tissue and
      absent or weakly expressed in unburned skin. Messenger RNA for tissue inhibitor
      of metalloproteinase-1 and -2 was consistently present in burned and unburned
      skin. By zymography, there was a significant increase in matrix metalloproteinase
      2 (twofold to threefold) and matrix metalloproteinase-9 (20- to 30-fold) activity
      in burned versus unburned skin. We suggest that postburn there is an upregulation
      of some matrix metalloproteinases that exceeds the level of inhibitors with the
      net result of an increase in proteolysis in burned tissue. This increased
      proteolysis may play a role in wound repair and scar formation.

PMID- 16984441
TI  - Chemokine and inflammatory cytokine changes during chronic wound healing.
AB  - Wound healing is a complex process resulting from an interplay of processes
      including coagulation, inflammation, angiogenesis, and epithelialization. The
      chemokine family has been shown to contain members that are potent regulators of
      many of these pathways. Because we have previously shown that chemokines "pool"
      in biologic wound dressings, we studied the levels of CXC and CC chemokines,
      along with key inflammatory mediators, serially from a group of patients
      undergoing therapy for chronic venous leg ulcers. After 8 weeks, all patients had
      marked clinical healing of their ulcers (median 63.3% reduction in size) with two
      of 10 completely healed. Wound fluids extracted from dressings showed high levels
      of platelet factor-4 and interferon-gamma-inducible protein, with a trend toward
      increases in the ratio of the sums of the angiogenic versus angiostatic CXC
      chemokines (p = 0.082) in the tissues collected from the center of the ulcers
      during wound closure. Neutrophil-activating peptide-2 and interleukin-8 accounted
      for the most changes in wound fluid angiogenic chemokines, with significant
      differences both as compared with baseline levels and with patients' plasma level
      noted at various time points between weeks 0 and 8. The level of angiostatic
      chemokines, interferon-y inducible protein 10 and platelet-activating-4, fell
      most significantly between weeks 0 and 3 as compared with plasma levels. The
      observed shift toward angiogenic CXC chemokines suggests that effective healing
      in chronic venous insufficiency ulcers appears to "move" the ulcer bed toward a
      state more conducive to epithelialization,characteristic of the proliferative
      phase of wound healing. CC chemokines were also elevated at baseline in the wound
      fluid samples as compared with the patients' plasma levels. Macrophage
      inflammatory protein-1 (3 and regulated on activation, normal T expressed and
      secreted (RANTES) levels decreased with healing, whereas there were significant
      increases in the tissue levels of monocyte chemoattractant protein-1 and
      macrophage inflammatory protein-1 a over the first 4 weeks of therapy (p< or =
      0.05 for both). Coincident with these changes was a steady increase in the ratio
      of interleukin-1 R/interleukin-1 receptor antagonist protein in the ulcer center
      tissues, which also correlated with healing (p < 0 .05) as compared with a
      decreasing ratio at the ulcer edge, and a biphasic response in the wound fluids.
      These findings suggest that advanced wound care techniques help move the ulcer
      from a chronic inflammatory state into one more characteristic of the late
      inflammatory/early proliferative phase of wound healing. Chemokines may play a
      critical role in the pathogenesis of chronic venous ulcers through their effects
      on angiogenesis and/or the progression of inflammatory reactions at the site of
      injury.

PMID- 16984442
TI  - Early tracheostomal healing in rabbits with use of various tracheal incisions.
AB  - Various tracheal incisions (vertical, horizontal, or window) are used by surgeons
      for creation of a tracheostomy. The inflammatory response and healing varies with
      each incision and may contribute to complications such as tracheal stenosis. This
      study evaluates the effect of these tracheotomies on early stomal wound healing
      in a rabbit model. Male juvenile New Zealand rabbits underwent tracheotomy, with
      each animal randomized to the type of tracheal incision used (vertical,
      horizontal, or window). After recovery, they were killed on postoperative days 2,
      4, 6, and 8, with tissue removed for histologic examination. Paraffin-embedded
      stomal sections were analyzed quantitatively for amounts of granulation tissue,
      fibrosis, and epithelization. Groups were compared statistically using chi
      square, ANOVA, Spearman's rho, and Mann-Whitney U tests with p less than 0.05
      considered significant. Fibrosis was significantly increased in the vertical and
      horizontal groups when compared with the window group. This increase was
      statistically significant between postoperative days 2 and 4 (p < 0.05). The
      amount of granulation tissue was only significantly increased in the window
      group, whereas no difference was seen in the rate at which epithelization
      occurred with the various incisions. Vertical and horizontal tracheal wounds have
      less granulation tissue formation and more fibrosis compared with window
      tracheotomies during initial wound healing. This could lead to a "safer"
      tracheostomy tract in the early postoperative period.

PMID- 16984443
TI  - Epidermal lipid metabolism of cultured skin substitutes during healing of full
      thickness wounds in athymic mice.
AB  - Cultured epidermal keratinocytes provide an abundant supply of biologic material
      for wound treatment. Because restoration of barrier function is a definitive
      criterion for efficacy of wound closure and depends on the lipids present in the
      epidermis, we analyzed lipid composition of the epidermis in cultured skin
      substitutes in vitro and after grafting to athymic mice. The cultured skin
      substitutes were prepared from human keratinocytes and fibroblasts attached to
      collagen-glycosaminoglycan substrates. After 14 days of incubation, cultured skin
      substitutes were grafted orthotopically onto full-thickness wounds in athymic
      mice. Samples for lipid analysis were collected after 14 and 34 days of in vitro
      incubation, and 3 weeks and 4 months after grafting. Both in vitro samples show
      disproportions in epidermal lipid profile as compared with the native human
      epidermis, i.e., a low amount of phospholipids (indicating imbalance in
      proliferation and differentiation); a large excess of triglycerides (storage
      lipids); and low levels of free fatty acids, gluco-sphingolipids, cholesterol
      sulfate, and ceramides-suggesting abnormal composition of stratum corneum barrier
      lipids. Fatty acid analysis of cultured skin substitutes in vitro revealed
      insufficient uptake of linoleic acid, which resulted in increased synthesis of
      and substitution with monounsaturated fatty acids, mainly oleic acid. These
      abnormalities were partially corrected by 3 weeks after grafting; and 4 months
      after grafting, all epidermal lipids, with some minor exceptions, were
      synthesized in proportions very similar to human epidermis. Results of this study
      show that grafting of cultured skin substitutes to a physiologic host permits the
      recovery of lipid in proportion to that required for barrier formation in normal
      human epidermis.

PMID- 16984444
TI  - Alpha-smooth muscle actin expression in rat and mouse mesenteric wounds after
      transforming growth factor-beta1 treatment.
AB  - Rat mesenteric perforations heal by contraction within 5 to 7 days, whereas mouse
      mesenteric perforations seldom close within 3 weeks unless stimulated by
      transforming growth factor-beta1. In this article, we quantified the expression
      of alpha-smooth muscle actin by quantitative-reverse transcription-polymerase
      chain reaction and the orientation of actin filaments at the wound margin by
      Fourier transformation image analysis after treatment with transforming growth
      factor-beta1. The expression of transforming growth factor-beta1 and its type II
      receptor was also assessed. Actin filaments were shown to increase with time at
      the wound margin in both species and the expression of alpha-smooth muscle actin
      mRNA increased simultaneously. Transforming growth factor-beta1 enhanced the
      alpha-smooth muscle actin expression four to five times in rats and three to four
      times in mice on day 5, but the number of copies expressed per cell was 15-fold
      higher in rats than in mice. Transforming growth factor-beta1 was down-regulated
      after wounding in free peritoneal cells of rats, but maintained until day 5 in
      transforming growth factor-beta1-treated mice. The main finding of this study was
      that untreated, normal rats expressed substantially more alpha-smooth muscle
      actin than mice. After treatment with transforming growth factor-beta1, this
      expression increased similarly in both species. It can be hypothesized that
      normal closure of mesenteric perforations requires a minimum level of actin
      expression. This level is not reached in normal mice, but is exceeded after
      stimulation. Perforations in the rat always close, because the alpha-smooth
      muscle actin expression is always above this level.

PMID- 16984445
TI  - Wound fluids from saline solution- and Staphylococcus aureus peptidoglycan
      inoculated sponges induce expression of matrix metalloproteinase 13 messenger
      ribonucleic acid by cultured rat fibroblasts.
AB  - Polyvinyl alcohol sponges inoculated with Staphylococcus aureus peptidoglycan
      induce an accelerated wound healing response when implanted subcutaneously in
      rats. S. aureus peptidoglycan leads to a marked increase (50%) in reparative
      tissue collagen (as measured by hydroxyproline) by 4 days. However, this effect
      drops by 7 days and by 14 days; hydroxyproline levels are similar in sponges
      inoculated with S. aureus peptidoglycan or saline solution. These data suggest a
      very active early remodeling process in S. aureus peptidoglycan sponge reparative
      tissue. Consistent with this observation, we had found that steady-state levels
      of matrix metalloproteinase-13 mRNA were higher and persisted longer in S. aureus
      peptidoglycan sponge reparative tissue than in controls. We hypothesized that S.
      aureus peptidoglycan might induce a change in reparative tissue fibroblast
      phenotype or modify the character of the wound fluid. Fibroblasts obtained from
      saline solution- and S. aureus peptidoglycan-inoculated sponges 4 days after
      subcutaneous implantation and cultured in Eagle's minimal essential medium
      supplemented with 10% fetal calf serum were similar with respect to morphologic
      features, proliferation, and expression of pro alpha1 (I) and alpha1 (III)
      collagens and tissue inhibitor of metalloproteinase-1 mRNA by Northern blot
      analysis. Neither cell type expressed matrix metalloproteinase-13 mRNA. No
      changes in the above parameters were detected when such fibroblasts were cultured
      for 24 hours in the presence of 0.5 mg of S. aureus peptidoglycan per 10 ml of
      medium or with fluid obtained from control sponges cultured for 12 hours with
      phosphate-buffered saline solution. Wound fluids extracted with Eagle's minimal
      essential medium by homogenization of saline solution- and S. aureus
      peptidoglycan-inoculated sponges implanted subcutaneously for 12 hours did not
      affect the proliferation of the fibroblasts. However, the extracts had a profound
      effect on the cellular expression of tissue inhibitor of metalloproteinase-1,
      matrix metalloproteinase-13, and pro alpha1 (I) collagen mRNA. Specifically,
      expression of matrix metalloproteinase-13 mRNA was induced, expression of pro
      alpha1 (I) collagen mRNA was reduced by 70%, and expression of tissue inhibitor
      of metalloproteinase-1 mRNA was increased by 150%. These changes were the same
      irrespective of whether the wound fluid was obtained from saline solution- or S.
      aureus peptidoglycan-inoculated sponges. Fluid obtained from S. aureus
      peptidoglycan-inoculated sponges, which contain a greater inflammatory exudate
      than saline solution-inoculated sponges do, is enriched in matrix
      metalloproteinase-13 mRNA-inducing activity. The nature of the factor(s) that
      induces matrix metalloproteinase-13 mRNA expression is not known. However,
      preliminary data suggest that the matrix metalloproteinase-13-inducing factor(s)
      is heterogeneous with regard to size and is temperature sensitive and trypsin
      resistant.

PMID- 16984446
TI  - Fibroblast growth factor-2 alters the effect of eroding polylactide-polyglycolide
      on angiogenesis in the bone chamber.
AB  - The effects of recombinant human fibroblast growth factor-2 in the presence of
      eroding 50:50 poly(DL-lactide-co-glycolide) on angiogenesis during acute bone
      defect healing were studied in the optical bone chamber. Bone chambers were
      loaded with disks of poly(DL-lactide-co-glycolide) surrounded by one of four
      doses of recombinant human fibroblast growth factor-2. Fifty-two female rabbit
      right tibias were implanted. Commencing with the third postimplantation week,
      healing into the bone chamber compartment was observed weekly, with use of
      intravital microscopy, until week 8. The treatment groups were as follows:
      unloaded, loaded with polymer only, and loaded with polymer plus-0.5, -1.0, and 
      10 microg recombinant human fibroblast growth factor-2. Videotaped and
      photographed bone images were measured and analyzed with a frame-grabber
      digitizing system. Comparison with controls or polymer alone revealed that
      angiogenesis rates were significantly above normal in rabbits loaded with polymer
      plus either of the two highest recombinant human fibroblast growth factor-2
      doses. The effects of these doses were not, however, significantly different from
      each other, indicating a plateauing rather than monotonically increasing
      response. It was concluded that recombinant human fibroblast growth factor-2 in
      the dose- range studied can effectively overcome the retarding effects of eroding
      polymer on angiogenesis in bone, which has been reported previously by this
      laboratory. In contrast to these results, no statistically significant
      differences in angiogenesis rate as a function of time could be detected. It is
      suggested that this apparent lack of variation is linked to observed alterations
      in vessel patterns from week-to-week. The clinical relevance of these results is
      that inhibitory carrier effects can be compensated for by increasing the dose of
      loaded agent where the effect being inhibited is the one being treated, or by
      adding an agent specific for the inhibited effect. In either case, geometry of
      the carrier must be considered when programming for delivery rate.

PMID- 16984447
TI  - Staphylococcus aureus peptidoglycan ameliorates cyclophosphamide-induced
      impairment of wound healing.
AB  - Cyclophosphamide given systemically to rats leads to impaired wound healing,
      characterized by decreases in the inflammatory reaction, fibroplasia,
      neovascularization, reparative collagen accumulation, and wound breaking
      strength. In contrast, the local application of Staphylococcus aureus
      peptidoglycan at the time of wounding increases all of these processes in normal
      rats. Accordingly, we hypothesized that inoculation of S. aureus peptidoglycan
      into wounds of cyclophosphamide-treated rats would ameliorate the otherwise
      impaired healing. Dorsal bilateral skin incisions and subcutaneous implantation
      of polyvinyl alcohol sponges (two on each side) were performed on male Sprague
      Dawley rats receiving either saline or cyclophosphamide (24 mg/kg)
      intraperitoneally at the time of operation, on postoperative days 1, 2, 3, 4 (for
      rats killed on postoperative day 7), and also on day 8 (for rats killed on
      postoperative day 14). The incisions on one side were inoculated at the time of
      closure with 0.2 ml of saline solution, and the incisions on the other side with
      6 mg S. aureus peptidoglycan in 0.2 ml saline solution (860 microg/cm incision).
      The sponges were instilled with 0.1 ml saline solution on the saline solution
      instilled incision side or with S. aureus peptidoglycan 0.5 mg/sponge) in 0.1 ml
      saline solution on the other side. In control rats receiving saline solution
      intraperitoneally, incisions treated with S. aureus peptidoglycan were
      significantly stronger than saline solution-treated incisions by a factor of 1.8
      at 1 week (p < 0.001); at 2 weeks the increase was small and not significant.
      Cardiac blood leukocytes and platelets fell markedly (90%) in cyclophosphamide-
      treated rats, and there was a decrease in wound breaking strength of their saline
      treated incisions at both 7 and 14 days compared with saline solution-treated
      incisions of control rats. S. aureus peptidoglycan treatment of the wounds
      completely prevented this effect at 7 days, and partially at 14 days. Polyvinyl
      alcohol sponge reparative tissue hydroxyproline, 7 days after surgery, was
      decreased in cyclophosphamide-treated rats; this was completely prevented by S.
      aureus peptidoglycan treatment of the sponges. Histologically, the inflammatory
      response to the wounding, influx of macrophages and fibroblasts, angiogenesis,
      and collagen accumulation were all reduced at day 7 and 14 after surgery in the
      sponge reparative tissue of cyclophosphamide- treated rats; this was prevented by
      S. aureus peptidoglycan treatment of the sponges. In conclusion, a single local
      application of S. aureus peptidoglycan ameliorates cyclophosphamide-impaired
      wound healing.

PMID- 16984451
TI  - Hereditary disorders of connective tissue: a review.
AB  - Extracellular matrix is a very complex assemblage of specialized molecules
      including collagen, elastin, proteoglycans, and attachment glycoproteins such as
      fibronectin and laminin. Collagen is an unusual protein because it requires
      multiple processing steps both within and outside the cell beginning with
      transcription and refinement of its messenger RNA, translation of the mature
      mRNA, extensive post-translational modifications, and further alterations in the
      extracellular compartments. If errors are made at any one of the multiple steps
      in this complex pathway, a defective molecule will be formed that could result in
      connective tissue abnormalities. Similarly, alterations in other components of
      the extracellular matrix can also result in clinical pathologies. Some of these
      clinical phenotypes have been classified as Ehlers-Danlos syndrome, Marfan
      syndrome, osteogenesis imperfecta, and epidermolysis bullosa. This article
      reviews these various connective tissue disorders, describes the underlying
      biochemical defects, and describes their impact on tissue repair.

PMID- 16984452
TI  - The role of growth factors in the healing of chronic wounds.
AB  - The clinical use of growth factors for the treatment of nonhealing human wounds
      holds great therapeutic potential. However, numerous clinical studies of
      recombinant growth factors used to treat chronic dermal wounds have generally
      reported disappointing results. Part of the explanation for these results may be
      a lack of appreciation of three basic principles related to the biology of wound
      healing and pharmaceutic considerations. Above all, the growth factor selected
      for a particular nonhealing wound must regulate a process of healing which is
      predominantly involved in healing that wound. A growth factor which stimulates
      epithelialization will be of little good in a wound which needs to heal by
      connective tissue deposition. Once the appropriate biologic modifier has been
      identified, one must be assured that there is a deficiency of that modifier in
      the wound environment. Finally, one must be sure that the delivery of the growth
      factor to the wound is in sufficient amount and duration to produce a biologic
      response. These considerations are exemplified with several clinical studies
      which did show improvement in the rate of healing of chronic wounds. Only when
      clinical trials are undertaken in which these tenets are incorporated in the
      study design will the true potential of various growth factors be appropriately
      determined.

PMID- 16984453
TI  - Low-frequency ultrasound treatment of chronic venous ulcers.
AB  - In a randomized controlled clinical trial, the properties of low-frequency
      ultrasound in the treatment of chronic venous ulcers were investigated. Thirty
      eight patients with chronic ulcerations of the legs caused by chronic venous
      insufficiency were randomly assigned to receive either conventional therapy alone
      or conventional therapy plus additional 30 kHz ultrasound treatment. Patients
      with other conditions that may impair wound healing such as diabetes mellitus or
      arterial disease were excluded. The ultrasound treatment consisted of 10 minutes
      of foot bathing with application of 30 kHz ultrasound 100 mW/cm(2) three times a
      week. Response was evaluated with the use of planimetry of the ulcer area and
      compared with controls after 3 and 8 weeks. After 3 weeks of treatment (and to a
      greater extent after 8 weeks of treatment) the ultrasound group showed a markedly
      better response than the control group. Although the control group showed a mean
      decrease of 11% in the ulcerated area after 8 weeks, in the ultrasound group the
      mean ulcerated area decreased by 41% (p < 0.05). There were only mild side
      effects in some of the patients treated with ultrasound. In conclusion,
      application of low-frequency ultrasound may be a helpful treatment option in
      chronic venous leg ulcers.

PMID- 16984454
TI  - Ability of chronic wound fluids to degrade peptide growth factors is associated
      with increased levels of elastase activity and diminished levels of proteinase
      inhibitors.
AB  - The stability of peptide growth factors exposed to fluids from healing surgical
      wounds and from nonhealing chronic wounds was examined in vitro. (125)I-Labeled
      transforming growth factor-beta1 or platelet-derived growth factor-BB was
      incubated with fluids from healing surgical wounds and fluids from venous stasis
      or pressure ulcers. Fluids from healing surgical wounds had no appreciable effect
      on the level of (125)I corresponding to intact growth factor. In contrast,
      incubation with fluids from several venous stasis or pressure ulcers resulted in
      significant degradation of these growth factors. Degradation was blocked by broad
      spectrum serine proteinase inhibitors and by specific inhibitors of neutrophil
      elastase. Levels of elastase activity in wound fluids correlated with the ability
      to degrade peptide growth factors. Further comparisons showed qualitative and
      quantitative differences in the endogenous proteinase inhibitors, alpha2
      macroglobulin and alpha1-antiproteinase. These results could explain, in part,
      the variable growth factor levels which have been found in chronic wounds. More
      importantly, the ability of some chronic nonhealing wounds to rapidly degrade
      exogenously added growth factors has important implications with regard to past
      and future clinical attempts to use peptide growth factors to treat these types
      of problem wounds.

PMID- 16984455
TI  - Hyaluronan: a potential carrier for growth factors for the healing of ligamentous
      tissues.
AB  - The anterior cruciate ligament has little capacity to heal after injury, in
      contrast to the medial collateral ligament. Cell migration and cell proliferation
      are essential steps in the wound healing of connective tissue, and we have
      developed an in vitro assay to study cell outgrowth (i.e., both cell migration
      and cell proliferation) from tissue explants. Using this assay, we have
      previously shown a synergistic effect of four growth factors on the early stages
      of cell outgrowth (i.e., at days 3 and 6) from these explants. Hyaluronan, a
      linear polysaccharide with a molecular weight of 3 x 10(6) daltons, has been
      shown to enhance the anterior cruciate ligament healing capacity in vivo by over
      50%. The purpose of this study was to assess in vitro whether hyaluronan and the
      combination of growth factors (transforming growth factor-beta1 25 ng/ml,
      platelet-derived growth factor-BB 100 ng/ml, basic fibroblast growth factor 100
      ng/ml, and insulin 25 microg/ml) would enhance cell outgrowth from explants at 3
      and 6 days. At 3 days the mean cell outgrowth from the explants treated with
      hyaluronan and the combination of growth factors exceeded the growth in the
      explants treated with growth factors alone for the anterior cruciate ligament
      (mean cell count +/- standard error: 19 +/- 4 and 2 +/- 1 cells, respectively)
      and for the medial collateral ligament (297 +/- 40 and 87 +/- 18 cells,
      respectively). At 6 days, the mean cell outgrowth in the presence of growth
      factors was enhanced sixfold by hyaluronan for the anterior cruciate ligament
      (160 +/- 27 compared with 26 +/- 15 cells) and fourfold for the medial collateral
      ligament (1363 +/- 219 compared with 330 +/- 74 cells). As previously shown,
      little cell outgrowth occurred from the anterior cruciate or medial collateral
      ligament explants when no growth factors were added to the modified Eagle's media
      at 3 and 6 days (<20 cells). For the medial collateral ligament only, hyaluronan
      had a small stimulatory effect on cell outgrowth in minimal essential media in
      the absence of growth factors. At 3 days the stimulation by hyaluronan was
      fourfold (31 +/- 8 cells compared with 7 +/- 4 cells), and at 6 days the
      stimulation by hyaluronan was nearly fourfold (73 +/- 17 compared with 20 +/- 12
      cells). These results suggest that hyaluronan could be used together with growth
      factors in efforts to enhance the healing of ligamentous tissue injuries.

PMID- 16984456
TI  - Mammalian wound repair environment does not permit skeletal muscle regeneration.
AB  - Repair and regeneration are mutually exclusive responses to injury. Previous
      studies have shown that wound fluids promote proliferation, but not
      differentiation, of myoblasts in vitro. This study explored the ability of the
      repair environment within polyvinyl alcohol sponges to support cellular events of
      skeletal muscle regeneration in vivo. Neonatal rat L8 myoblasts were modified to
      express beta-galactosidase then inoculated into plain sponges or sponges
      containing minced muscle. Labeled myoblasts were found in myotubes within minced
      muscle. In contrast, myoblasts inoculated into sponges lacking muscle remained
      mononucleate. Occurrence of labeled myoblasts within myotubes, which required
      fusion, represents differentiation of inoculated myoblasts to participate in
      regeneration. Failure of myoblasts to form myotubes in sponges lacking muscle
      suggests that this wound repair environment cannot support morphologic
      differentiation of myoblasts. Although this repair environment can support the
      survival of myoblasts, it did not support myogenesis, an event necessary to
      complete skeletal muscle regeneration. Data from this study reinforce earlier
      studies in vitro and suggest that the properties attributed to wound fluids are
      inherent in the wound environment. Whether the inability of this environment to
      support myogenesis is the consequence of the absence of essential factors or the
      presence of inhibitors remains to be determined.

PMID- 16984457
TI  - Transition from fetal to adult repair occurring in mouse forelimbs maintained in
      organ culture.
AB  - In previous wound healing experiments with the use of midgestation murine fetal
      forelimb explants, wounds were made before or immediately after amputation from
      the fetus. This experimental technique allows one to ask the question: do
      circulatory elements initiate or sustain the repair process in vitro? The
      hypotheses tested in the current study were that repair occurs in organ culture
      in the absence of systemic influences and that the in vivo transition from fetal
      like to adult-type repair persists in an unperfused in vitro system. Gestational
      day-14 mouse forelimbs were harvested and placed in serum-free culture medium.
      Before amputation, control forelimbs received linear full-incision microscalpel
      wounds that were closed primarily. The animals in the other group were not
      immediately wounded but cultured for 4 days and then wounded with primary wound
      closure. All limbs were cultured for 7 days after wounding and then processed for
      histologic analysis. In the immediately wounded limbs, scarless healing occurred
      with collagen fibers deposited in a reticular form. In contrast, the delay
      wounded limbs had collagen organized in parallel arrays (disordered),
      constituting repair by scarring. Wound repair proceeded as a local phenomenon in
      the absence of systemic mediators. We conclude that day-14 gestation forelimbs
      undergo maturation in culture, causing a transition from scarless to adult scar
      repair.

PMID- 16984458
TI  - Comparisons of wound healing among excisional, laser-created, and standard
      thermal burns in porcine wounds of equal depth.
AB  - The present study was designed to characterize similarities and differences among
      three wounding modalities in partial-thickness porcine wounds. We hypothesized
      that inherent differences, such as endogenous cytokine delivery into excisional
      wounds or ablation of eschar during laser vaporization, should accelerate the
      magnitude and sequence of reparative events above the delayed repair that is
      frequently observed in patients with burns. A constant mid-dermal depth of injury
      was created by a Padgett dermatome, a computer-controlled pulsed CO(2) laser, or
      a temperature-controlled metal template. Wounds were harvested after 5, 10, or 15
      days. After 5 days, significant resurfacing differences were apparent with values
      of 54% in excisions, 29% in lasers, and 12% in standard thermal burns. Sequences
      of fibroblastic proliferation were measurably different among the three wound
      modalities. At day 5 the bromodeoxyuridine labeling index for fibroblasts showed
      laser wound levels greater than excision wound levels, which were greater than
      burn wound levels; but by day 10, the proliferative profiles indicated that burn
      wound levels were greater than excision wound levels, which were greater than
      laser wound levels. Capillary areas (an assessment of angiogenesis) differed
      among the three wound types throughout the study. Peak values were observed at
      day 5 in both excisional and laser injuries; however, standard thermal burns did
      not peak until day 10. Both the magnitude and sequence of expression of three
      matrix metalloproteinases (-1, -2, and -9) differed among the three types of
      injuries. Laser wounds showed the earliest peak in matrix metalloproteinase-1
      expression, whereas burns showed the least expression at day 5. In conclusion,
      although the three types of wounds undergo similar reparative processes such as
      reepithelialization, fibroblastic proliferation, angiogenesis, and expression of
      matrix metalloproteinases, the magnitude and temporal sequences are measurably
      altered among the three wound modalities. A greater understanding of specific
      differences within wound environments may lead to more insightful design of
      interventional wound therapies.

PMID- 16984459
TI  - Rate of tendon gap closure in an in vitro collagen gel matrix.
AB  - Tendon gap closure was examined in a tissue culture model and found to have a
      similar time course as skin wound closure. Foot tendons from White Rock chickens
      were mounted in a collagen gel matrix and maintained with the use of Dulbecco's
      modified Eagle medium, containing fetal calf serum and antibiotics, for 4 weeks
      at 37 degrees C in an incubator. Gap distances between tendons were measured
      every 1 to 3 days and plotted against time as the contraction curve. After an
      initial lag period of 4 to 8 days, gap distance showed a progressive decrease.
      Gap closure rate was defined as the slope of the contraction curve, and it was
      found to be a function of initial gap distance (r = 0.643, p 0.045). The time
      necessary to reduce the initial gap distance by half had a significant
      correlation with the initial gap distance (r = 0.986, p < 0.001). Fibroblast
      migration began on days 2 to 3 after a 1- to 2-day lag period. Fibroblasts were
      visible in the tendon gap region before the start of collagen gel contraction. At
      this time, the fibroblast migration rate was 0.33 mm/day. A critical density of
      fibroblasts was necessary to start collagen gel contraction. Once the gap
      distance began to diminish, fibroblast migration measurements were hampered
      because the measurable area was decreasing. Collagen gel contraction reduced the
      measurable fibroblast migration rate by nearly half to 0.18 mm/day. A linear
      correlation was found between fibroblast distance traveled and time in culture
      during both the gel lag and gel contraction time periods. This tendon culture
      model may be potentially useful for wound healing studies because it allows for
      studies of fibroblast activity in the early lag phase when the cells populate the
      collagen lattice but before contraction of the gel occurs.

PMID- 16984460
TI  - In vitro analysis of adhesion molecule expression and gel contraction of human
      granulation fibroblasts.
AB  - The objective of this study was to determine whether human fibroblasts obtained
      at different times from normally healing wounds were phenotypically distinct with
      respect to cell-matrix interactions. We cultured human granulation fibroblasts
      obtained from repeated biopsies from the same punch area. On days 3, 6, 9, and 14
      the expression of key adhesion molecules and extracellular matrix components at
      the protein level by flow cytometry analysis were compared with quiescent
      fibroblasts. Intercellular adhesion molecule-1 levels were significantly elevated
      only around day 3, which implies a phenotypic change during the early phase of
      wound healing. Homing cell adhesion molecule, as well as the alpha4 integrin
      subunit (CD49d), were essentially unaltered. The alpha5 integrin subunit (CD49e),
      which imparts the specificity of the fibronectin receptor and alphav (CD51), a
      vitronectin receptor component, are upregulated around days 3 and 6; the alpha2
      and 3 integrin subunits (CD49b/c) were only increased on day 6. In granulation
      fibroblasts, at days 3 and 14, the level of the beta1 integrin subunit was
      enhanced. In addition, collagen gel contraction with granulation fibroblasts
      increases constantly from day 3 to day 14. These results show that human
      granulation fibroblasts differentially express cell surface adhesion molecules
      depending on the age of the healing wound. Further, changes in the ability of
      these cells to contract collagen gels indicate a synchronicity between wound bed
      contraction and different stages of wound healing.

PMID- 16984461
TI  - Reversal of the wound healing deficit in diabetic rats by combined basic
      fibroblast growth factor and transforming growth factor-beta1 therapy.
AB  - Wound healing is impaired in the diabetic state because of, at least in part, low
      expression of growth factors. Individual growth factors can partially activate
      healing, yet the actual wound environment presents a dynamic continuum of
      multiple cellular signals. Complex interactions among growth factors and target
      cells can have synergistic effects, and several examples of combinatorial, in
      vivo activity are evident in the literature. In this study, the implantation of a
      combination of basic fibroblast growth factor and transforming growth factor-beta
      in rats induced fivefold to sevenfold increases in granulation tissue formation
      in comparison with implantation of each growth factor alone. Diabetes was induced
      in adult, male Sprague-Dawley rats with streptozotocin. Incisional wounds and
      sponge granulation tissue were produced in separate groups and then treated with
      an injection of 2 microg transforming growth factor-beta1 combined with 10 microg
      basic fibroblast growth factor on day 3. DNA, collagen, and protein were analyzed
      in granulation tissue on days 7 and 9, and biomechanical properties of incisions
      were tested on days 7, 14, and 21. The combination of transforming growth factor
      beta1 and basic fibroblast growth factor had marked, positive effects on
      biochemical parameters of wound healing and reversed the tensile strength deficit
      of diabetic wounds. Nonradioactive in situ hybridization showed increased
      expression of messenger RNA for type I and III procollagen and transforming
      growth factor-beta1 in normal and diabetic wounds, whereas ultrastructural
      examination showed a marked reorganization of collagen fibrils. These findings
      reinforce the concept that appropriate mixtures of cytokines rather than
      individual cytokines may more adequately stimulate tissues in cases of impaired
      wound healing.

PMID- 16984462
TI  - Postsurgical intraperitoneal exposure to glove powders modulates inflammatory and
      immune-related cytokine production.
AB  - The objective of the present study was to determine whether intraperitoneal
      exposure to glove powders modulates the inflammatory and immune responses by
      altering the influx of inflammatory and immune cells and peritoneal fluid
      cytokines and thus the outcome of surgically induced peritoneal wound healing.
      Peritoneal wall injuries were made by scraping the tissue until bleeding occurred
      in 360 mice. One of the following fluids was then introduced into the peritoneal
      cavity: phosphate-buffered saline solution, phosphate-buffered saline solution
      containing glove powders (Biosorb and Keoflo, 100 microg/ml), Hydrocote (Hydrogel
      film, Biogel 100 microg/ml), latex proteins (1 mg/ml), or lipopolysaccharides
      (12.5 microg/ml). At intervals of 1 to 28 days after injury, 10 mice per
      treatment per day and 10 uninjured mice were killed, peritoneal fluids were
      collected to determine the cytokine levels, the rate of fibrous adhesions formed
      at the site of injuries was graded, and peritoneal walls with attached fibrous
      adhesions were removed to determine the degree of inflammatory and immune cell
      infiltration into the wound. The results indicated that, with the exception of
      interferon-gamma, the peritoneal fluid levels of transforming growth factor
      beta1, tumor necrosis factor-alpha, interleukin-1beta, and granulocyte-macrophage
      colony stimulating factor in the phosphate-buffered saline solution-treated
      injured group significantly increased, reaching maximum between days 4 and 7 (p <
      0.05) compared with the uninjured group and returned to uninjured values by day
      14 after injury. The level of transforming growth factor-beta1 was higher in
      glove powders and Hydrocote-treated groups than in latex, lipo-saccharides, or
      phosphate-buffered saline solution-treated groups until day 14 after surgery (p <
      0.05). The levels of tumor necrosis factor-alpha and interleukin-1beta increased
      in all treatment groups during the first week after injury compared with
      uninjured controls, with the exception of Hydrocote. The number of T
      helper/inducers (CD4), total leukocytes (CD11a), B lymphocytes (CD45R),
      granulocytes (Gr-1), and mononuclear phagocytes (Mac-3) in the wound increased
      during the first week after peritoneal wounding with no significant difference
      between treated and untreated groups. The rate of adhesion formation was not
      significantly altered in treated compared with untreated groups. These data
      suggest that a mechanism which mediates glove powder-induced peritoneal
      inflammatory and immune reactions in the postsurgical setting involves
      augmentation of cytokine production without influencing the influx of
      inflammatory and immune cells or adhesion formation.

PMID- 16984464
TI  - Can we increase the estimated value of semen assessment?
AB  - Estimating the fertility of a semen sample or of the male from where it has been
      collected by simple assessment of in vitro sperm characteristics is still
      difficult, owing to the variable correlations that laboratory results achieve
      with in vivo fertility. A major reason behind these variations is the fact that
      the ejaculate and the artificial insemination (AI)-doses it generates are
      composed of a diverse sperm population. Such heterogeneity is reflected both in
      differences of intactness of attributes needed for fertilization, such as
      motility or morphology, but also in the relative ability of spermatozoa to
      prevail fertile over time, handling and exposure to different stimuli, all of
      which account for innate variations in fertilizing ability among doses,
      ejaculates and sires. However, methods are already available to select sub
      populations of intact spermatozoa which can be tested for their degree of
      competence for fertilization and whose estimated power is promising, allowing the
      elimination of cases of sub-fertility, particularly in bovine. Examples of these
      methods are the separation of viable spermatozoa by swim-up or discontinuous
      gradient centrifugation, followed by testing the ability of the selected
      spermatozoa to dose-response/time sustain capacitation and acrosome reaction
      induction. Finding how large a sperm population with non-compensated attributes
      for fertilization and ability to display and sustain stimuli is, perhaps by a
      quick screening of membrane integrity and stability by multi-parametric methods,
      would allow, provided the particular male produces this sub-population in a
      repeatable manner, for a better estimation of fertility.

PMID- 16984465
TI  - Mammalian sperm energy resources management and survival during conservation in
      refrigeration.
AB  - The present review has as its main aim to present an overview regarding the
      mechanisms utilized by mammalian sperm to manage its intracellular energy levels.
      This management will strongly influence the sperm's ability to maintain its
      overall function during its entire life span. Thus, the precise knowledge of
      these mechanisms will be of the utmost interest to optimize the systems utilized
      to conserve mammalian sperm for a medium-to-long time-lapse. Briefly, utilization
      of hexoses as energy substrates by mammalian sperm is very finely regulated from
      the very first step of its metabolization. Furthermore, the equilibrium among the
      separate, monosaccharide metabolization pathways in mammalian sperm depends on
      many factors. This prevents the possibility to draw a general vision of sperm
      energy utilization, which explains the results of all mammalian species in all
      points of the sperm life-cycle. To complicate the matter further, there are
      separate energy phenotypes among mammalian spermatozoa. The precise knowledge of
      these phenotypes is of the greatest importance in order to optimize the design of
      new extenders for sperm conservation in refrigerated conditions. Moreover, sugars
      can act on sperm not only as passive metabolic substrates, but also as direct
      function activators through mechanisms like specific changes in the tyrosine
      phosphorylation status of distinct proteins. Finally, mammalian sperm utilizes
      non-glucidic substrates like citrate and lactate to obtain energy in a regular
      form. This utilization is also finely regulated and of importance to maintain
      overall sperm function. This implies that the exact proportion of glucidic and
      non-glucidic energy substrates could be very important to optimize the survival
      ability of these cells in conservation.

PMID- 16984466
TI  - Semen technologies in dog breeding: an update.
AB  - Pure dog breeding is experiencing growing interest. Assisted reproductive
      technologies are each time demanded more by the small animal practitioner. In
      this paper different semen technologies are briefly reviewed under the
      perspective of the authors. In addition, new trends in the evaluation of canine
      ejaculates, developed in the laboratory of the authors are discussed. The
      existence of sperm subpopulations defined based both on kinematics and
      morphometric characteristics of the spermatozoa is now widely accepted by the
      scientific community. In the laboratory of the authors new, simpler and more
      straightforward statistical tools have been used to disclose the sperm
      subpopulation structure in the canine ejaculate. The study of the sperm
      subpopulation structure and its changes after cryopreservation has allowed us to
      gain an insight into the differences in freezeability among dogs, and also
      predict to a great extent the outcome of a cryopreservation procedure of a given
      semen sample. New techniques to evaluate early membrane changes have also been
      recently developed in our laboratory.

PMID- 16984467
TI  - Improvement strategies in ovine artificial insemination.
AB  - Artificial insemination in ram is scarcely widespread comparing with other
      domestic species. This has been due not only to fertility results being irregular
      and low but also because of the difficulty in the application of enhancements
      such as the use of frozen-thawed sperm. Although there is a lot of information on
      the use of different options to improve these AI results (such as transcervical
      application, the use of thawed sperm, etc.) commercial programmes can be
      classified on two general categories: those using refrigerated semen (15 degrees
      C) by superficial intracervical deposition (vaginal), and, more restricted, those
      using thawed sperm by intrauterine deposition (laparoscopy). In the present work,
      we have summarized our viewpoint on three general research lines for the
      improvement of AI results in sheep: semen preservation, AI procedures and semen
      assessment. Briefly, in ram it is necessary to develop a medium term methodology
      of sperm refrigeration (3-5 days), which would allow the distribution of sperm
      doses to a widespread area. Nevertheless, it is also necessary to develop an
      intrauterine transcervical AI technique, which allows thawed semen to be applied
      by vaginal insemination. Besides, the low predictive value of classic assessment
      techniques limits the ability to adjust the number of spermatozoa per dose
      according to its actual fertility.

PMID- 16984468
TI  - Challenges in pig artificial insemination.
AB  - Semen extended in a liquid state, together with conventional artificial
      insemination (AI), is the sole sperm technology used by the pig industry. Sperm
      technologies known for many years, such as cryopreservation, and others developed
      during recent years, such as sperm sexing, have not yet been integrated into
      commercial use. Moreover, there has recently been an explosion of new
      technologies, such as sperm mediated gene transfer or encapsulated spermatozoa
      which need additional supportive techniques before they can be economically
      applied to pig breeding. The speed with which the aforementioned sperm
      technologies are accepted and utilized by the pig industry depends on the
      availability of efficient insemination procedures. Therefore, AI is entering a
      new dimension where it will be converted into a tool for the efficient
      application of current and new sperm technologies. Some new insemination
      procedures have been recently developed. This review examines the suitability of
      available insemination procedures for the efficient application of current,
      emergent and future sperm technology to the pig industry.

PMID- 16984469
TI  - Developmental consequences of sexual dimorphism during pre-implantation embryonic
      development.
AB  - Abnormalities of development potential arising from pre-implantation environment
      are not limited to in vitro culture (IVC) (for, i.e. in ruminants the large
      offspring syndrome produced by IVC), they may also be consequence of specific
      stress conditions experienced in vivo, like maternal diet, toxins, etc. A complex
      group of mechanisms (gene expression, epigenetic, metabolic, etc.) may operate to
      link early embryo environment with future health. Furthermore, during the pre
      implantation period, in vitro produced male embryos have a higher metabolic rate,
      they grow faster than females, and they also have differential gene transcription
      of genes located in the Y-, X-, or in autosomal-chromosomes. As a consequence of
      these differences embryos may be affected differentially by natural or artificial
      environmental conditions, depending on their gender. It has been suggested that
      under some stress conditions male embryos are more vulnerable than females;
      however the biological fragility of male embryos is poorly understood. Evidences
      suggest that epigenetic differences produced by the presence of one or two X
      chromosomes are the principal cause of the male and female pre-implantation
      differences, and we put forward the possible role of these early sex differences
      to control sex ratio of the offspring under different environmental conditions in
      Nature. By following the differences between male and female early embryos not
      only may be possible to manipulate sex ratio in farm animals, we can also gain
      further insight into aspects of early embryo development, X inactivation, and
      epigenetic and genetic processes related with early development that may have a
      long-term effect on the offspring.

PMID- 16984470
TI  - Bovine early embryonic development and vitamin A.
AB  - Vitamin A and its derivatives, collectively termed as retinoids, have been paid
      attention in recent years because of their effects in bovine reproduction.
      However, the role of retinoids in the pre-implantation period continues to be
      largely unexplored, in contrast to later stages of development. Retinoids control
      cell growth, differentiation and death through binding to specific nuclear
      receptors by retinoic acid and other active metabolites. This paper reviews how
      retinoids can influence early embryonic development in cattle through their
      influence on the follicle, the extrafollicular oocyte and the pre-implantation
      embryo itself.

PMID- 16984471
TI  - Seasonal endocrine changes and breeding activity in mediterranean wild ruminants.
AB  - The methods of assisted reproduction commonly used in domestic animals are
      currently being applied to non-domestic species. This is because of the
      limitation of maintaining the genetic variability in the wild, as it occurs in
      wild ruminants of the Mediterranean Basin. Despite the apparent progress of the
      technology, success of the offspring to grow and become healthy adult individuals
      has remained low in wild species. Difficulties usually arise from insufficient
      information about basic reproductive biology, such as the seasonal changes in
      ovarian and testicular activity. Directional adaptive evolution involves
      development of speciespecific physiological reproductive patterns to cope with
      various environmental factors. Thus, species originating and living at the same
      latitude display different reproductive strategies to entrain the breeding
      activity at an optimal time of the year. The aim of this paper was to present
      current knowledge on reproductive physiology of Mediterranean wild ruminants as a
      basic prerequisite for the successful use of assisted reproduction methods.
      Special emphasis is given to seasonal endocrine changes, ovarian cycles and
      testicular activity of Iberian wild ruminants, together with the role of social
      interactions on the regulation of these events.

PMID- 16984472
TI  - Inbreeding and reproduction in endangered ungulates: preservation of genetic
      variation through the Organization of Genetic Resource Banks.
AB  - There is a constant increase in the number of species suffering marked reductions
      in population size. This reduction in size and the lack of genetic flow may lead
      to a decrease in genetic variability and to matings between close relatives (i.e.
      inbreeding) with an ensuing reduction in fitness. It is thus important to
      understand the mechanism underlying the deleterious effects of inbreeding and to
      develop reproductive biotechnologies that will allow the reduction of inbreeding
      depression by facilitating gene exchange between populations. The study of three
      endangered species of gazelles, Cuvier's gazelle (Gazella cuvieri), Mohor gazelle
      (Gazella dama mhorr) and dorcas gazelle (Gazella dorcas neglecta) has revealed
      that inbreeding negatively affects several semen parameters (motility, sperm
      morphology, acrosome integrity). Semen cryopreservation has been achieved in the
      three species but success varies depending on the diluent employed and the level
      of inbreeding. Artificial insemination of Mohor gazelles have led to the birth of
      the first gazelle born using frozen-thawed semen but improvements are needed
      before this technology can be applied on a routine basis for the genetic
      management of the populations. Collection of oocytes after ovarian stimulation,
      followed by in vitro maturation, fertilization and culture has met with some
      initial success in the Mohor gazelle. These, together with other reproductive
      technologies, will offer an invaluable help in preserving the maximum of genetic
      diversity of these and related endangered ungulate species.

PMID- 16984473
TI  - The application of reproductive technologies to natural populations of red deer.
AB  - Over the past decade, there has been increasing interest in the application of
      reproductive technology to the conservation and management of natural populations
      of deer. The application of assisted reproduction technologies within natural
      population of deer is in its infancy. However, its future potential is enormous,
      particularly in relation to genetic management or conservation. This paper
      reviews the present state of such technologies for a wild subspecies of red deer,
      the Iberian red deer (Cervus elaphus hispanicus), by discussing the major
      components of oestrous synchronization, semen collection/cryopreservation and
      insemination techniques. In addition, findings made during the course of studies
      on natural populations have enormous potential for the understanding of novel
      reproductive mechanism that may not be uncovered by livestock or human studies. A
      summary of these results are also reviewed here.

PMID- 16984487
TI  - Measuring marker information content by the ambiguity of block boundaries
      observed in dense SNP data.
AB  - Recent studies have noted that the boundary of common haplotype blocks in hapmap
      constructions involve a certain degree of ambiguity, and so do the resulting
      "tagSNPs". Here, we report how to address this issue at the level of individual
      SNP markers. We introduce a measure called the marker ambiguity score (MAS), and
      evaluate its utility by simulation studies based on a real dataset of 2949 SNPs
      spanning a region of 56.1M bp. We show that the MAS method can be used to assess
      the level of boundary ambiguity caused by varying ethnic background, sample sizes
      for hapmap construction, and disease aggregation. We find a striking difference
      in overall patterns of block boundary distributions in two ethnic groups (blacks
      and whites), and subtle changes in block structures that agree with the
      evolutionary history of the two populations. Our analyses suggest that a sample
      size of 200 or more subjects is probably needed for "stable" hapmap
      constructions. In addition, we demonstrate that there are subtle changes in block
      boundaries in hapmaps constructed in disease populations versus normal controls.
      This approach can quantify the information content of individual markers in the
      context of highly dense SNP data, which may have important implications in
      designing efficient genome-wide association mapping projects.

PMID- 16984488
TI  - Analysis of case-only studies accounting for genotyping error.
AB  - The case-only design provides one approach to assess possible interactions
      between genetic and environmental factors. It has been shown that if these
      factors are conditionally independent, then a case-only analysis is not only
      valid but also very efficient. However, a drawback of the case-only approach is
      that its conclusions may be biased by genotyping errors. In this paper, our main
      aim is to propose a method for analysis of case-only studies when these errors
      occur. We show that the bias can be adjusted through the use of internal
      validation data, which are obtained by genotyping some sampled individuals twice.
      Our analysis is based on a simple and yet highly efficient conditional likelihood
      approach. Simulation studies considered in this paper confirm that the new method
      has acceptable performance under genotyping errors.

PMID- 16984493
TI  - Systematic review: applications and future of gastric electrical stimulation.
AB  - BACKGROUND: Over the past 20 years, gastric electrical stimulation has received
      increasing attention among researchers and clinicians. AIM: To give a systematic
      review on the effects, mechanisms and applications of gastric electrical
      stimulation. METHODS: Medline was used to identify the articles to be included in
      this review. Key words used for the search included gastric electrical
      stimulation, gastric pacing, electrical stimulation, stomach, gastrointestinal
      motility, central nervous system, gastroparesis, nausea and vomiting; obesity and
      weight loss. Combinational uses of these keywords were made to identify relevant
      articles. Most of the articles included in this review ranged from 1985 to 2006.
      RESULTS: Based on the general search, the review was structured as follows: (i)
      peripheral and central effects and mechanisms of gastric electrical stimulation;
      (ii) clinical applications of gastric electrical stimulation for gastroparesis
      and obesity and (iii) future development of gastric electrical stimulation.
      CONCLUSIONS: Great progress has been made during the past decades. Gastric
      electrical stimulation has been shown to be effective in normalizing gastric
      dysrhythmia, accelerating gastric emptying and improving nausea and vomiting.
      Implantable device has been made available for treating gastroparesis as well as
      obesity. However, development of a new device and controlled clinical studies are
      required to further prove clinical efficacy of gastric electrical stimulation.

PMID- 16984494
TI  - Systematic review: lamivudine prophylaxis for chemotherapy-induced reactivation
      of chronic hepatitis B virus infection.
AB  - BACKGROUND: Reactivation of hepatitis B virus infection in asymptomatic hepatitis
      B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy
      is a well-documented and potentially fatal complication. Data supporting the use
      of lamivudine for primary prophylaxis have emerged, but its use remains
      controversial and is not standardized. AIM: To review current randomized
      controlled trials, randomized trials and prospective case series to provide a
      clinically applicable, evidence-based recommendation. METHODS: The published
      literature was identified using a MEDLINE/PubMed search with secondary review of
      cited publications, and inclusion of all prospective studies. RESULTS: In nine
      prospective trials and one randomized-controlled trial, the rate of hepatitis
      among subjects receiving lamivudine prophylaxis ranged from 0% to 20% (16 of 173,
      9.2%), compared with 33-67% among controls. Of patients receiving prophylaxis, 0
      24% (15 of 173, 8.7%) developed hepatitis B virus reactivation, compared with 29
      56% of controls. Three reactivation-related mortalities were reported (one
      receiving prophylaxis, two controls). No patients withdrew secondary to toxicity
      or development of lamivudine-resistant mutations. CONCLUSIONS: The available data
      show a four- to sevenfold decrease in the rate of hepatitis and hepatitis B virus
      reactivation in patients who receive lamivudine prophylaxis. It is thus
      recommended that all hepatitis B surface antigen carriers receive lamivudine, or
      a comparable anti-viral agent, as prophylaxis from the initiation of chemotherapy
      until at least 1 year following its completion.

PMID- 16984495
TI  - The effects of tegaserod on oesophageal function and bolus transport in healthy
      volunteers: studies using concurrent high-resolution manometry and
      videofluoroscopy.
AB  - BACKGROUND: Tegaserod is a partial 5-hydroxytryptamine 4 receptor agonist with
      prokinetic effects on the gastrointestinal tract, its effects on oesophageal
      function are unknown. AIM: A randomized, placebo controlled, double-blind trial
      assessed the effect of tegaserod on the oesophagus in healthy, asymptomatic
      subjects. METHOD: A 7-day course of tegaserod 6 mg b.d. vs. placebo was
      prescribed (n = 17/21 completed both phases of study). High-resolution manometry
      and pH measurements were performed before and after a test meal. Bolus transport
      of liquids and solids was studied by high-resolution manometry and
      videofluoroscopy. RESULTS: Tegaserod had no effect on lower oesophageal sphincter
      pressure compared with placebo, peristaltic velocity increased (P < 0.001) and
      distal contractile pressure decreased slightly (P < 0.05). Transient lower
      oesophageal sphincter relaxations and reflux were infrequent regardless of
      treatment. During the studies of bolus transport, high-resolution manometry
      revealed that tegaserod promoted mid-oesophageal contractility (P < 0.02) and
      shortened the 'proximal transition zone' (P < 0.05), the level where bolus escape
      occurred most frequently. These effects had no effect on liquid bolus transport;
      however a non-significant trend to improved solid bolus transport was observed
      (66% vs. 31%;P = 0.07). CONCLUSION: Tegaserod did not alter lower oesophageal
      sphincter pressure, but had significant effects on peristaltic function. High
      resolution manometry promoted mid-oesophageal contractility during bolus
      transport. This effect was associated with a non-significant trend to improved
      solid bolus transit.

PMID- 16984496
TI  - The effect of sildenafil on segmental oesophageal motility and gastro-oesophageal
      reflux.
AB  - BACKGROUND: Sildenafil is an inhibitor of type 5 phosphodiesterase. It relaxes or
      inhibits contraction of smooth muscle by increasing cellular concentrations of
      cyclic guanosine monophosphate. Multichannel intraluminal impedance manometry/pH
      allow the precise evaluation of oesophageal bolus transit and acid/non-acid
      reflux. AIM: To investigate the effect of sildenafil on segmental oesophageal
      motor function and gastro-oesophageal reflux. METHODS: Eight healthy volunteers
      underwent multichannel intraluminal impedance manometry baseline, and 15, 30 and
      45 min before and after a 50-mg dose of sildenafil successively. The subjects
      underwent 2-h multichannel intraluminal impedance/pH studies on two separate days
      after either water or sildenafil ingestion. RESULTS: Sildenafil decreased the
      resting lower oesophageal sphincter pressure and prolonged the duration of lower
      oesophageal sphincter relaxation for the 45 min following its ingestion. At 15
      min, distal onset velocity, total bolus transit time, bolus presence time and
      segmental transit time were delayed in the mid to distal oesophagus. At 30 min,
      distal onset velocity was restored but bolus presence time and bolus presence
      time were still delayed in distal smooth muscle segment. At 45 min, total bolus
      transit time and distal onset velocity were restored but bolus presence time and
      segmental transit time were delayed more in the transition zone. Sildenafil did
      not alter the reflux. CONCLUSION: Sildenafil alters lower oesophageal sphincter
      function and oesophageal bolus transit, but not induce gastro-oesophageal reflux.

PMID- 16984497
TI  - Effect of a proton pump inhibitor on postprandial gastric volume, emptying and
      symptoms in healthy human subjects: a pilot study.
AB  - BACKGROUND: In consensus guidelines, proton pump inhibitors (PPIs) are
      recommended for the treatment of functional dyspepsia. It is unclear whether PPIs
      change gastric volume or emptying. AIM: To assess the effect of a PPI,
      rabeprazole, on gastric volume and emptying and postprandial symptoms. METHODS:
      In a double-blind, parallel-group placebo-controlled trial, 13 healthy
      participants were randomized to rabeprazole, 20 mg b.d., or placebo. On day 3,
      fasting gastric volume was measured using intravenous (99m)Tc-pertechnate and
      single photon emission computed tomography (SPECT). After the last dose of study
      medication, an (111)In-chloride egg meal (300 kcal) was ingested, and
      postprandial gastric volume and emptying were measured by SPECT. Symptom ratings
      using a visual analogue scale (fullness, nausea, bloating, abdominal pain,
      aggregate score) were obtained at baseline and 15, 30, 45, 60 and 75 min
      postprandially. Group comparisons were performed using Mann-Whitney rank sum
      test. RESULTS: There were no statistically significant differences in gastric
      volume or emptying in the two groups. However, there was a borderline increase in
      gastric volume with rabeprazole compared with placebo. Rabeprazole treatment
      reduced aggregate postprandial symptoms, particularly fullness, 30 min after the
      meal (P = 0.01). CONCLUSIONS: In healthy participants, rabeprazole, 20 mg b.d.,
      did not significantly change gastric emptying, but reduced symptoms and had a
      borderline effect on gastric volume postprandially. The mechanism of reduced
      postprandial symptoms with a PPI requires further study.

PMID- 16984498
TI  - Influence of delaying gastric emptying on meal-related symptoms in healthy
      subjects.
AB  - BACKGROUND: Although delayed gastric emptying is often found in functional
      dyspepsia, a causal role for delayed emptying in inducing symptoms has not been
      demonstrated. AIM: To investigate the influence of delaying gastric emptying rate
      in healthy volunteers on the occurrence of meal-related symptoms. METHODS:
      Fourteen healthy subjects (six men, mean age 23 +/- 1) underwent gastric emptying
      studies twice using the 14C octanoic acid and 13C glycin breath test after pre
      treatment with saline or sumatriptan 6 mg s.c. Breath samples were taken before
      meal and at 15-min intervals for a period of 360 min postprandially. At each
      breath sampling, the subject was asked to grade the intensity (0-6) of four
      dyspeptic symptoms. RESULTS: Sumatriptan pre-treatment significantly delayed
      solid but not liquid gastric emptying (t1/2 respectively 159 +/- 11 vs. 112 +/- 9
      min, P < 0.005 and 134 +/- 11 vs. 116 +/- 12 min, N.S.). Sumatriptan
      significantly decreased the mean cumulative symptom score (21.3 +/- 5.5 vs. 8.0
      +/- 2.6, P = 0.01), as well as scores for each individual symptom. CONCLUSION: A
      moderate delay in gastric emptying in health is not associated with an increase
      of meal-related symptoms. This observation argues against a causal role for
      delayed gastric emptying in the pathogenesis of dyspeptic symptoms.

PMID- 16984499
TI  - Type I autoimmune hepatitis: clinical course and outcome in an Italian
      multicentre study.
AB  - BACKGROUND: Many reports of autoimmune hepatitis (AIH) were written in the 'pre
      Hepatitis C era' and data on the natural history are still incomplete. AIM: To
      evaluate the clinical presentation and the natural history of type I AIH.
      METHODS: Seventy-three consecutive patients with a regular follow-up of at least
      2 years were prospectively included in the study. The mean follow-up was 91 +/-
      61 months. RESULTS: Patients with 'acute' onset at presentation were
      significantly older than patients with 'chronic' onset (P < 0.05) and had
      significantly higher serum levels of transaminase, gamma-glutamyltransferase and
      bilirubin; Prothrombin time was significantly lower in the said group compared
      with AIH patients with 'chronic' onset. In 4 of 63 (6.3%) female patients, AIH
      had the onset during pregnancy; in all of them the outcome of pregnancy was
      favourable. The major events during the follow-up included oesophageal varices (n
      = 9) and ascites (n = 4), and 60 patients remained in remission while receiving
      immunosuppression. None of the patients died during the follow-up, but seven
      patients were transplanted. The cumulative transplant-free probability of
      survival was 73.5% at 280 months. CONCLUSIONS: Elderly patients have more
      frequently an acute onset at presentation. Survival in AIH is apparently good;
      with early diagnosis, and improved medical therapy, liver transplantation for AIH
      will become a rare event in future.

PMID- 16984500
TI  - Endoscopic sphincterotomy with or without cholecystectomy for choledocholithiasis
      in high-risk surgical patients: a decision analysis.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) is recommended for patients with
      choledocholithiasis after ERCP with sphincterotomy (ES) and stone extraction.
      AIM: We designed a decision model to address whether ES alone versus ES followed
      by LC (ES + LC) is the optimal treatment in high-risk patients with
      choledocholithiasis. METHODS: Our cohort were patients with obstructive jaundice
      who have undergone an ES with biliary clearance. Recurrent biliary complications
      over a 2-year period stratified by gallbladder status (in/out) and age-stratified
      surgical complication rates were obtained from the literature. Failure of therapy
      was defined as either recurrent symptoms or death attributed to biliary
      complications. RESULTS: For age 70-79 years, ES failed in 15% whereas ES + LC
      failed in 17% of cases. Mortality in the EC + LC group was 3.4 times that of the
      ES alone cohort. For age 80+ years, ES was dominant with an incremental success
      rate of 8%. Mortality in the ES + LC was 7.6 times that of ES. For age <70, ES +
      LC was the dominant strategy with an incremental success rate 5%. Sensitivity
      analysis in the groups confirmed our conclusions. CONCLUSIONS: Management of
      choledocholithiasis by ES and stone clearance, but without cholecystectomy,
      should be considered for patients aged 70+. For low-risk patients, ES + LC should
      be performed to prevent recurrent biliary complications.

PMID- 16984501
TI  - Cost-effectiveness of growth factors during hepatitis C anti-viral therapy.
AB  - BACKGROUND: Although the current standard of care for controlling anaemia and
      neutropenia during anti-viral therapy for hepatitis C is to use dose reduction of
      ribavirin and pegylated interferon, respectively, erythropoietin and granulocyte
      colony-stimulating factor are now being advocated as alternatives to dose
      reduction. AIM: To determine the cost-effectiveness of erythropoietin and
      granulocyte colony-stimulating factor as an alternative to anti-viral dose
      reduction during antihepatitis C therapy. METHODS: Decision analysis was used to
      assess cost-effectiveness by estimating the cost of using a growth factor per
      quality-adjusted life-year gained. RESULTS: Under baseline assumptions, the cost
      per quality-adjusted life-year of using growth factors ranged from 16,247 US
      dollars for genotype 1 with neutropenia to 145,468 US dollars for genotype 2/3
      patients with anaemia. These findings are sensitive to the relationship between
      dose reduction and sustained virological response. CONCLUSIONS: Based upon our
      findings and the varying strength of the evidence for a relationship between dose
      reduction and sustained virological response: granulocyte colony-stimulating
      factor may be cost-effective for genotype 1 patients; erythropoietin is probably
      not cost-effective for genotype 2/3 patients; no conclusion can be reached
      regarding the cost-effectiveness of erythropoietin for genotype 1 patients or
      granulocyte colony-stimulating factor for genotype 2/3 patients. Randomized
      trials are needed to firmly establish the relationship between dose reduction and
      sustained virological response.

PMID- 16984502
TI  - A randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without
      amantadine in the re-treatment of patients with chronic hepatitis C not
      responding to standard interferon and ribavirin.
AB  - BACKGROUND: There is yet no established treatment for chronic hepatitis C
      patients non-responder to standard interferon and ribavirin. AIM: To evaluate
      efficacy and safety of pegylated-interferon-alpha2a plus ribavirin with or
      without amantadine in such patients. METHODS: 161 non-responders to standard
      interferon and ribavirin were randomized into two groups: 81 patients (Group 1)
      were given weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily
      for 12 months, 80 patients (Group 2) received weekly Peg-IFN-alpha2a 180 microg
      plus ribavirin 1,000-1,200 mg/daily and amantadine 200 mg/daily for 12 months.
      RESULTS: At the end of follow-up, HCV-RNA was negative in 29.6% of Group 1 and in
      21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded
      better to bi-therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among
      patients with genotypes 2 and 3 there was a trend towards a higher sustained
      virological response rate when retreated with triple treatment (80% vs. 75%, P =
      0.82). On multivariate analysis, genotype 1 or 4, high body mass index and >20%
      reduction of Peg-interferon were associated with the treatment failure.
      CONCLUSIONS: The addition of amantadine does not improve the overall SVR rate in
      non-responder patients retreated with Peg-IFN and ribavirin; however, about 30%
      of non-responders may achieve a sustained response, in particular patients with
      genotypes 2 and 3 show a high SVR (75%).

PMID- 16984503
TI  - Once daily MMX mesalazine for the treatment of mild-to-moderate ulcerative
      colitis: a phase II, dose-ranging study.
AB  - BACKGROUND: SPD476 (MMX mesalazine), is a novel, once daily, high-strength
      mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System (MMX)
      technology to delay and extend delivery of the active drug throughout the colon.
      AIM: To assess the safety and efficacy of MMX mesalazine in patients with mild-to
      moderately active ulcerative colitis, in a pilot, phase II, randomized,
      multicentre, double-blind, parallel-group, dose-ranging study (SPD476-202).
      METHODS: Thirty-eight patients with mild-to-moderately active ulcerative colitis
      were randomized to MMX mesalazine 1.2, 2.4 or 4.8 g/day given once daily for 8
      weeks. Remission ulcerative colitis-disease activity index (UC-DAI) < or =1, a
      score of 0 for rectal bleeding and stool frequency, and > or =1 -point reduction
      in sigmoidoscopy score from baseline was the primary end point. RESULTS: Week 8
      remission rates were 0%, 31% and 18% of patients receiving MMX mesalazine 1.2,
      2.4 and 4.8 g/day respectively. No statistically significant difference in
      remission was observed between treatment groups. MMX mesalazine 2.4 and 4.8 g/day
      groups demonstrated greater improvement in overall UC-DAI and component scores
      from baseline, compared with the 1.2 g/day group. CONCLUSION: MMX mesalazine
      given as 2.4 or 4.8 g/day once daily is well tolerated and effective for the
      treatment of mild-to-moderately active ulcerative colitis.

PMID- 16984504
TI  - Adherence rates with infliximab therapy in Crohn's disease.
AB  - BACKGROUND: Inflammatory bowel disease is associated with non-adherence to
      treatment with oral medications. AIM: To assess the intravenous infliximab
      adherence rate and identify risk factors for non-adherence to treatment. METHODS:
      Infliximab infusion dates for 1 June 2002-30 October 2003 were obtained.
      Additional information was obtained from two other administrative and patient
      based databases. Non-adherence was defined as a 'No Show' designation for a
      scheduled appointment. Non-adherence rate, odds ratios for associations to 'No
      Show' appointments and analysis were performed to identify patient
      characteristics associated with non-adherent behaviour. RESULTS: One thousand
      hundred and eighty-five infliximab infusions were scheduled for 274 patients.
      Forty-eight (4%) of appointments were classified as 'No Show'. Six patients
      accounted for 13/48 (27%) of failed appointments; another 35 patients missed one
      appointment. 'No Show' appointments were more likely to be for female patients,
      those on concomitant immunomodulators and those >18 weeks from initial infusion.
      Patients who missed >1 appointment were more likely to be female and have
      Medicaid vs. those with only one missed appointment (P < 0.05). Indication,
      patient area code and race were not significantly associated with single or
      repeated No Show behaviour. CONCLUSIONS: Overall, the non-adherence rate for
      infliximab is low. Risk factors that may contribute to non-adherence to treatment
      include female gender and maintenance dosing.

PMID- 16984505
TI  - The +1059G/C polymorphism in the C-reactive protein (CRP) gene is associated with
      involvement of the terminal ileum and decreased serum CRP levels in patients with
      Crohn's disease.
AB  - BACKGROUND: Serum C-reactive protein (CRP) levels influence the response to anti
      tumour necrosis factor (TNF) therapies. AIM: To analyse the influence of the
      +1059G/C CRP polymorphism on CRP serum levels and disease susceptibility in
      patients with Crohn's disease (CD). METHODS: Using restriction fragment length
      polymorphism (RFLP) analysis, genomic DNA from 241 CD patients and 199 unrelated
      controls was analysed for the +1059G/C substitution in the CRP gene and the
      common caspase-activation recruitment domain 15 (CARD15) variants. RESULTS:
      Homozygous C/C carriers were detected only among CD patients (P = 0.066).
      Patients with ileal involvement (L1 and L3 phenotype) were found in only 58.4% of
      patients with the wildtype G/G genotype but in 88.2% of the heterozygous G/C
      carriers (OR 5.26; 95% CI 1.19-23.92) and four of the five C/C homozygous
      carriers (80%; OR 4.55; 95% CI 1.64-16.67; P = 0.008 for hetero- and homozygous
      carriers vs. wildtype) which was independent of the presence of CARD15 variants.
      Increased CD activity was associated with increased CRP serum levels (P < 0.005).
      For Crohn's disease activity index (CDAI) < 150, C/C homozygosity for the +1059
      G/C polymorphism was associated with significantly lower CRP serum levels (P <
      0.01). CONCLUSIONS: The C allele of the CRP +1059G/C polymorphism is associated
      with decreased serum CRP levels and increased likelihood of disease involvement
      of the terminal ileum in CD patients.

PMID- 16984506
TI  - Participation in a clinical trial influences the future management of patients
      with gastro-oesophageal reflux disease in general practice.
AB  - BACKGROUND: The long-term effects of participation in trials has not been
      reported. A randomized-controlled trial (the ONE study) reported on the
      management of gastro-oesophageal reflux disease with esomeprazole in primary
      care, testing on-demand treatment vs. treatment courses. AIM: To evaluate the
      impact of participation in a trial on General Practitioners management and
      patient behaviour. METHODS: Management of gastro-oesophageal reflux disease was
      compared between General Practitioners who participated in ONE (ONE-GPs) and a
      random sample of General Practitioners who did not participate in ONE (Other
      GPs). Symptom presentation and satisfaction with treatment was compared between
      patients who had participated in ONE (ONE-patients) and patients who had not
      (Other-patients). RESULTS: ONE-GPs prescribed on-demand treatment with proton
      pump inhibitors to 47% of the patients, Other-GPs to 27%. ONE-patients consulted
      for significantly less symptoms compared with Other-patients. ONE-patients
      reported significantly higher patient satisfaction compared with Other-patients.
      ONE-patients used 98 doses during 6 months whereas Other-patients used 76 doses.
      CONCLUSIONS: Participation in a clinical trial influenced both doctors and
      patients. Treatment modalities introduced by the trial were used in daily
      practice by the General Practitioners. Patients who had participated in the trial
      consulted for less symptoms and used more medication, compared with patients who
      did not participate.

PMID- 16984507
TI  - Adipokines and gastrointestinal disease.

PMID- 16984509
TI  - Effect of sera on the adhesion of natural killer cells to the endothelium in
      severe pre-eclampsia.
AB  - OBJECTIVE: To investigate the effect of serum on the interaction between natural
      killer (NK) cells and endothelial cells in pre-eclampsia. METHODS: Seven severely
      pre-eclamptic patients, five normal pregnant women, and four normal non-pregnant
      women were included in this study. Freshly isolated NK cells labeled with
      Chromium-51 were incubated on an endothelial cell monolayer in the presence of
      patient serum. In regard to the characteristics of adhesive molecules, the
      endothelial cells were blocked by monoclonal antibodies (mAbs) to intracellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1); the NK
      cells were blocked by mAbs to leukocyte function-associated antigen (LFA-1) and
      very late antigen-4 (VLA-4) before co-incubation. After incubation, the adherent
      cells were solubilized with 1% Triton X. The lysates were collected and counted
      in a gamma counter. RESULTS: The adhesion of NK cells to the endothelium in the
      normal pregnancy group decreased significantly in comparison to the non-pregnant
      group (7%vs 72%; P < 0.01). Adhesion in the severe pre-eclamptic group was
      significantly higher in comparison to the normal pregnant group (44%vs 7%; P <
      0.01). The blocking percentages of mAbs on NK adhesion in the severe pre
      eclampsia group were 49 +/- 4% to LFA-1, 61 +/- 48%, 67 +/- 39% to VLA-4, ICAM-1,
      and 68 +/- 7% to VCAM-1. CONCLUSION: Sera from normal pregnant women suppress the
      adhesion between NK cells and endothelial cells, whereas the suppressive effect
      of sera from pre-eclamptic patients has a diminished affect.

PMID- 16984510
TI  - In vivo expression and antitumor activity of p53 gene transfer with naked plasmid
      DNA in an ovarian cancer xenograft model in nude mice.
AB  - INTRODUCTION: Abnormalities in the p53 and p16 tumor suppressor genes are one of
      the most common occurrences associated with human neoplasia. Consequently,
      restoration of wild-type p53 or p16 functions is seen as a particularly promising
      approach for cancer gene therapy. In vitro and in vivo data have demonstrated
      that virus-mediated p53 gene transfer can induce active cell death and ovarian
      tumor regression. AIM: To evaluate the efficiency of intratumoral injection of
      naked DNA in tumor growth inhibition in an ovarian xenograft model. For that
      purpose, plasmid vectors encoding wild-type p53 (wt-p53) or p16 alone or in
      combination were used. METHODS: Nude mice were injected subcutaneously with the
      human ovarian adenocarcinoma cell line SKOV3. Three weeks after xenograft, tumor
      bearing mice were injected twice a week with plasmid vectors carrying WT-p53
      and/or WT-p16 cDNA. Empty plasmids and saline buffer were used as control. Tumor
      growth was monitored to evaluate the inhibition potential with p53 and/or p16
      restoration. RESULTS: When compared to the control, intratumoral repeated
      injections of naked plasmid DNA encoding wt-p53 were inhibiting tumor growth.
      This inhibition was not observed with p16 and no synergy could be obtained
      between p53 and p16. p53 expression was restored in 84% of mice injected with
      plasmid encoding wt-p53. p16 expression was restored in 63% of mice injected with
      plasmid encoding p16. CONCLUSIONS: In this report we demonstrated that: (i) naked
      DNA represents an efficient gene transfer in the SKOV3 xenograft model; (ii)
      restoration of wt-p53 gene allows tumor growth inhibition; and (iii) this
      inhibition could be correlated with p53 expression as seen in 84% of treated mice
      after repeated naked DNA injections. These results allow us to envisage naked DNA
      as a therapeutic adjuvant in ovarian cancer treatment, concomitantly with tumor
      resection and chemotherapy.

PMID- 16984511
TI  - Loss of hMLH1 expression is associated with less aggressive clinicopathological
      features in sporadic endometrioid endometrial adenocarcinoma.
AB  - AIM: To assess the incidence and clinicopathological significance of
      microsatellite instability (MSI) and the protein expression of hMLH1 and hMSH2 in
      sporadic endometrioid endometrial adenocarcinoma (SEEA). METHODS: A total of 50
      patients with pure endometrioid sporadic endometrial adenocarcinoma were enrolled
      in the study. MSI analysis was done using five polymorphic markers (BAT26,
      D5S346, BAT25, D17S250, D2S123) and the protein expression of the hMLH1 and hMSH2
      genes was determined by immunohistochemical staining. MSI was detected in 24%
      (12/50) of SEEA cases. RESULTS: There was a significant correlation between MSI
      status and loss of hMLH1, hMSH2 expression, respectively. No significant
      association was found between MSI status and clinicopathological parameters,
      including age, grade, stage, depth of myometrial invasion, lymph-vascular space
      invasion (LVI), lymph node involvement or peritoneal cytology. However,
      significant correlations were found between loss of hMLH1 and a lower
      histological grade and the absence of LVI in patients with SEEA. CONCLUSIONS:
      According to these results, MSI and a loss of protein expression of hMLH1 and
      hMSH2 may be associated with the pathogenesis of SEEA. In addition, hMLH1
      immunostaining might have a role as a prognostic parameter. Further research
      using a large number of cases is needed to confirm our observations.

PMID- 16984512
TI  - Rubella outbreak on Tokunoshima Island in 2004: serological and epidemiological
      analysis of pregnant women with rubella.
AB  - AIM: This paper presents the serological and epidemiological background of the
      rubella-infected pregnant women following the rubella outbreak throughout
      Tokunoshima Island that occurred after the revision of the immunization law in
      Japan. METHODS: Twelve of 149 pregnant women managed in Miyagami Hospital were
      enrolled as having a high risk for congenital rubella infection. They were
      interviewed about their immunization history with rubella vaccine, the presence
      of rash, onset of rash, and the presence and timing of contact with rubella
      infected patients. The obstetric histories were investigated for past rubella HI
      antibody titer. Nine of 12 women continued their pregnancy and delivered a baby.
      A serological test for rubella IgM antibody and a reversed transcription-nested
      PCR assay using umbilical cord blood and the newborn urine for virus genome
      detection were performed for all babies. We also enrolled all 309 mothers who
      delivered during the last 2 years in Miyagami Hospital, and retrospectively
      collected their rubella HI titers. RESULTS: Congenital rubella syndrome (CRS) and
      congenitally infected babies were born from 12 high-risk mothers. In our study,
      six pregnant women to be immunized by a catch-up program showed a lack of
      immunity to rubella. The remaining six women had low rubella immunity. Nine
      acquired rubella from members of their family, including their husband. The
      incidence of negative HI titer was 25% in women less than 25 years old who
      delivered during the last 2 years in this hospital. CONCLUSIONS: More intensive
      immunization should be considered to eradicate CRS completely in Japan.

PMID- 16984513
TI  - Three-dimensional assessment of the morphology of the umbilical artery in normal
      and pre-eclamptic placentas.
AB  - AIM: Pre-eclampsia is one of the main causes of intrauterine growth retardation.
      Although there are many studies performed in this setting showing the course of
      the umbilical vessels within the umbilical cord along with its structural
      changes, studies are lacking with regard to intraplacental vasculature and its
      structural changes. METHODS: We investigated whether the vascular pattern
      differed in preeclamptic placentas in terms of intraplacental course and
      morphometry of the umbilical artery by using vascular corrosion cast technique.
      Furthermore, cross-sections taken from umbilical artery branches at different
      levels within the placenta, were examined with both light and scanning electron
      microscopy (SEM). RESULTS: Vascular corrosion casts generated in both pregnancy
      groups should be defined with the main umbilical artery divided into 2-4 primary
      branches. No significant difference was seen between normal and pre-eclamptic
      groups regarding the diameters of primary and secondary branches and the number
      of cotyledons contained (P > 0.05). However, microscopic studies demonstrated
      expanded intervillous spaces in the placentas of pre-eclamptic pregnancies. Under
      SEM, distortion on the endothelial surface of the umbilical artery and an
      increase in vessel diameter and wall thickness have been determined in pre
      eclamptic placentas. Furthermore, the branching pattern and changes affecting the
      endothelial surface of the umbilical artery have been shown three-dimensionally
      in pre-eclamptic placentas, using corrosion cast technique and SEM, respectively.
      CONCLUSION: While microscopic findings were consistent with the Doppler
      ultrasonography findings, namely higher systole/diastole ratio and increased
      resistance (RI) and pulsatile (PI) index in the umbilical artery, no clear
      morphometric change has been observed.

PMID- 16984514
TI  - Does marriage between first cousins have any predictive value for maternal and
      perinatal outcomes in pre-eclampsia?
AB  - AIM: To assess the consequences of consanguineous unions between first cousins on
      the severity of pre-eclampsia and associated perinatal morbidity. METHODS: Six
      hundred and eighty-six women admitted with a diagnosis of pre-eclampsia were
      included. The study group consisted of 62 preeclamptic women with a union between
      first cousins. The remaining patients admitted throughout the same period (n =
      624) served as controls. The groups were compared regarding the presence of
      severe pre-eclampsia, hemolysis elevated liver enzymes low platelets (HELLP)
      syndrome, eclampsia, placental abruption, hematological complications, renal
      failure, requirement for antihypertensive or magnesium sulfate treatments,
      cesarean section for acute fetal distress, birthweight, Apgar scores, perinatal
      mortality and neonatal morbidity including admission to the neonatal intensive
      care unit, respiratory distress syndrome, sepsis, convulsions, intracranial
      hemorrhage, hypoglycemia, hypocalcemia, and jaundice. Student's t-test, chi(2)
      test and logistic regression analysis were used for statistical evaluation.
      RESULTS: Univariate analysis yielded significant differences in parity (P =
      0.034), maternal platelet counts (P = 0.02), and maternal serum potassium levels
      (P = 0.016) among the groups. Respiratory distress syndrome was more frequent (P
      = 0.043) in infants of unrelated couples. Multivariate analysis, controlling for
      the confounding factors, revealed that marriages between first cousins had no
      effect on any of our outcome variables including neonatal respiratory distress
      syndrome. CONCLUSIONS: Third-degree consanguinity in terms of a union between
      first cousins seems to have no effect on the development of maternal and
      perinatal complications in established pre-eclampsia.

PMID- 16984515
TI  - Comparative study of induction of labor in nulliparous women with premature
      rupture of membranes at term compared to those with intact membranes: duration of
      labor and mode of delivery.
AB  - AIM: To evaluate the effect of premature rupture of membranes (PROM) at term on
      the duration of labor and mode of delivery in comparison with intact membranes in
      nulliparous women with an unfavorable cervix whose labor was induced. METHODS:
      This retrospective cohort study included all term nulliparous women with an
      unfavorable cervix requiring labor induction over a 2-year period. Prostaglandin
      E(2) (dinoprostone) and oxytocin were used for labor induction. Criteria for
      enrolment included (i) singleton pregnancy; (ii) term nulliparous women; or (iii)
      Bishop score below 6. Statistics were analyzed with Student's t-test, chi(2)
      test, Fisher's exact test, and multiple logistic regression. RESULTS: Our study
      subjects were 82 women whose labor was induced for PROM and 219 women with intact
      membranes whose labor was induced for social or fetal reasons. The mean durations
      of active phase of labor were not significantly different between women with PROM
      and those with intact membranes. However, the women with PROM had a significantly
      longer mean duration of second stage and a higher rate of cesarean delivery for
      failure to progress than those with intact membranes. Multiple logistic
      regression demonstrated that only PROM and fetal macrosomia were significantly
      associated with an increased risk of cesarean delivery for failure to progress
      after other confounding variables were adjusted. CONCLUSIONS: Labor induction for
      PROM at term in nulliparous women with an unfavorable cervix is associated with
      longer duration of the second stage and a higher risk of cesarean delivery for
      failure to progress in comparison to those with intact membranes.

PMID- 16984516
TI  - Reducing postpartum hemorrhage in Vietnam: assessing the effectiveness of active
      management of third-stage labor.
AB  - AIM: The study was undertaken to meet the need of the Ministry of Health to have
      local evidence on the effectiveness of active management of third-stage labor
      (AMTSL) in reducing the incidence of postpartum hemorrhage (PPH) > or = 500 mL
      and the need for PPH treatment. METHODS: Using a quasi-experimental design, AMTSL
      was introduced for all births attended by government midwives (at home,
      community, and district levels) in one district while standard practice without
      AMTSL was continued in three neighboring districts (with a 1:2 ratio of
      participants). Oxytocin (10 IU) was administered either by standard disposable
      syringe and needle or by a prefilled, single-use injection device. Postpartum
      blood loss was estimated using standard containers; other outcome measures
      included the duration of third stage, the need for additional treatments, and
      final maternal condition. A total of 3607 women participated (1236 in the
      intervention district and 2371 in the comparison districts). Multivariate
      logistic regression was used to control for age, parity, place of delivery, and
      first-stage oxytocin augmentation. RESULTS: AMTSL was associated with reduced
      risks for prolonged third stage beyond 30 min (odds ratio [OR] = 0.20, 95%;
      confidence interval [CI]: 0.11, 0.35), supplemental oxytocin (OR = 0.68, 95% CI:
      0.49, 0.94), and bimanual compression (OR = 0.63, 95%; CI: 0.41, 0.98). When
      cases with first-stage oxytocin augmentation were excluded, AMTSL was associated
      with a 34% reduction in PPH incidence (OR = 0.66, 95%; CI: 0.45, 0.98).
      CONCLUSION: This study supports the value of AMTSL in reducing the incidence of
      PPH, shortening the third stage of labor, and reducing the need for additional
      treatments.

PMID- 16984517
TI  - Association between serum tumor necrosis factor-alpha and corticotropin-releasing
      hormone levels in women with preterm labor.
AB  - AIM: To evaluate the association of serum corticotropin-releasing hormone (CRH)
      and tumor necrosis factor-alpha (TNF-alpha) in preterm labor. METHODS: Forty-nine
      primigravidas with a singleton viable pregnancy between 28 and 34 weeks of
      gestation were studied. They were divided into two groups. Group A consisted of
      30 pregnant women (mean gestational age: 30.6 week) who presented with preterm
      labor and group B consisted of 19 pregnant women (mean gestational age: 29.8
      week) with normal pregnancies. RESULTS: Women of group A had significantly higher
      serum CRH levels compared to those of group B (P < 0.01). Similarly, serum TNF
      alpha levels were significantly higher in women of group A when compared to women
      of group B (7.8 +/- 3.72 pg/mL and 5.1 +/- 3.72 pg/mL, respectively).
      Furthermore, a positive correlation was found between serum CRH and TNF-alpha
      levels in both groups, which was stronger in women of group A. CONCLUSIONS: Our
      findings suggest that the increased levels of TNF-alpha and CRH found in pregnant
      women presenting with preterm labor may be involved in the pathophysiological
      mechanism of the latter. Furthermore, a positive interaction may exist between
      TNF-alpha and placental CRH, which may lead to enhanced production of the second
      and, therefore, facilitate the onset of labor.

PMID- 16984518
TI  - Role of aromatase inhibitor in ovulation induction in patients with poor response
      to clomiphene citrate.
AB  - AIM: To examine the efficacy of aromatase inhibitor in the induction of
      ovulation. METHODS: This prospective clinical trial in patients with infertility
      and poor response to clomiphene citrate (CC) was undertaken in a tertiary
      referral infertility clinic. Thirty-five infertile patients, who were treated by
      clomiphene citrate for several cycles and referred to the infertility clinic,
      were the target population. Initially, the response of CC was assessed by same
      dose of CC that the patient had in her last cycle. The patients who did not
      respond adequately were treated by aromatase inhibitor 2.5-5 mg/day from day 3-7
      of the menstrual cycle. The main outcome measures were the number of mature
      follicles, ovulation rate, endometrial thickness and pregnancy rate. RESULTS:
      Twenty-seven (90%) patients developed mature follicles by day 12. The majority
      (77.77%) developed single follicle. Except for one cycle of one patient, the
      follicles of all patients were ruptured in all cycles and seven (25.94%) got
      pregnant. CONCLUSION: The aromatase inhibitor letrozole is effective for
      ovulation induction in anovulatory infertility in patients that failed to ovulate
      by CC.

PMID- 16984519
TI  - Effects of ovarian drilling in middle Black Sea region Turkish women with
      polycystic ovary syndrome having normal and high body mass indices.
AB  - AIM: To assess the effectiveness of laparoscopic ovarian drilling (LOD) in women
      with polycystic ovary syndrome (PCOS) with normal and high body mass indices
      (BMIs). METHODS: We investigated the effects of LOD process on two different
      groups of Turkish women with normal (n = 13) and high (n = 12) body mass indices.
      Three-puncture laparoscopy was performed under general anesthesia. Luteinizing
      hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone-sulfate
      (DHEAS) and total testosterone (total T) levels were measured one menstrual cycle
      before the operation (in early follicular phase defined as day 3 of the menstrual
      cycle) and one menstrual cycle after the operation (in early follicular phase
      defined as day 3 of the menstrual cycle). RESULTS: Ovarian drilling had a
      positive effect on FSH increase and DHEAS, total testosterone and LH/FSH ratio
      decrease; but BMI levels had no effect on these hormonal changes, respectively (F
      = 0.343, P = 0564) (F = 0.790, P = 0383) (F = 0.083, P = 0776) and (F = 0.816, P
      = 0376). Ovarian drilling had a positive effect on LH decrease and BMIs were
      effective on this change (F = 6.946, P < 0.05). LH decrease in the group with
      normal BMI was significantly higher than the obese group with high BMI. Ten of 13
      women with normal BMI (76.9%) and eight of 12 women with high BMI (66.6%) started
      to see regular menses 2 to 3 months after the procedure. CONCLUSION: Ovarian
      drilling is an effective procedure on PCOS. Women with lower BMI may benefit more
      from the procedure.

PMID- 16984520
TI  - Precedence of the shift of body-fat distribution over the change in body
      composition after menopause.
AB  - AIM: This study investigated the sequence of certain phenomena after menopause:
      decrease in bone mineral density (BMD), change in body composition (lean and fat
      components), and the shift toward upper body fat distribution. METHODS: Subjects
      were 188 postmenopausal women aged 50-65 years old. They were divided into four
      subgroups based on 4-year increments in age. Regularly menstruating women (n =
      51) aged 50-53 years old served as controls. Age, height, weight, and years since
      menopause were recorded. Body fat mass, percentage of body fat (%fat), lean body
      mass (LBM), lumbar spine (L2-4), total body BMD, and the trunk-leg fat mass ratio
      were measured by dual-energy X-ray absorptiometry. RESULTS: In postmenopausal
      women (n = 42) aged 50-53 years, BMD was lower compared to age-matched controls
      (P < 0.05), while other variables did not differ. Trunk-leg fat mass ratio in
      women aged 54-57 years or more was significantly higher than that in control. LBM
      was significantly lower while percentage fat was significantly higher in women
      aged 58-61 years old or more. CONCLUSION: An initial event during the menopausal
      process is BMD loss, which is followed by body fat distribution shift, then LBM
      loss and reciprocal increase in body fat mass.

PMID- 16984521
TI  - Delivery of a healthy twin after intrauterine demise and expulsion of a first
      twin.
AB  - We report on a diamniotic-dichorionic twin pregnancy after in vitro
      fertilization. The first twin was diagnosed with Down syndrome and spontaneously
      aborted at 24 weeks of gestation after intrauterine death at week 18. The second
      healthy twin was delivered by cesarean section 11 weeks later. We discuss
      management aspects and review the literature.

PMID- 16984522
TI  - Pure uterine lipoma.
AB  - Pure fatty tumors of the uterus are extremely rare and usually develop in
      postmenopausal women. We present the first reported Japanese case of a pure
      uterine lipoma, in which a preoperative diagnosis was made by magnetic resonance
      imaging (MRI) and was pathologically confirmed postoperatively. As in our case,
      MRI is currently the best modality for determining the internal architecture of a
      tumor and the presence of fat. Because of the benign nature of a uterine lipoma,
      such an approach can avoid unnecessary surgery in asymptomatic patients.

PMID- 16984523
TI  - Primary ovarian fibrosarcoma with long-term survival: a report of two cases.
AB  - We report on two cases of primary ovarian fibrosarcoma detected in two women aged
      44 and 34 years old. In the first case, an 18 x 17 x 10 cm multilobular tumor was
      detected in the left ovary. In the second case, a 13 x 9 x 3 cm and a 7 x 6 x 2
      cm tumor were found in the left and right ovaries, respectively. In addition, a
      large quantity of ascitic fluid was detected. In both cases, a total hysterectomy
      with bilateral adnexectomy and an omentectomy were performed. No evidence of
      lymph-node enlargement was detected in either case. Microscopic findings
      demonstrated densely, cellular spindle-shaped tumor cells with increased mitotic
      activity (17 and 8/10 high-power fields, respectively). Immunohistochemical
      analyses showed that tumor cells were positive for vimentin and negative for
      smooth muscle actin, S-100, and estrogen receptor. Progesterone receptor was
      positive only in the second case. After surgery, both patients received several
      courses of combination chemotherapy. Neither patient demonstrated any evidence of
      disease recurrence during follow-up for 10 years and 5 years, respectively.

PMID- 16984524
TI  - Occurrence of fetal choroid plexus cysts in siblings.

PMID- 16984525
TI  - Gastroesophageal reflux and lung transplantation.

PMID- 16984526
TI  - Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett
      esophagus and esophageal adenocarcinoma.
AB  - The aim of this study was to examine the association of obesity with esophageal
      adenocarcinoma, and with the precursor lesions Barrett esophagus and
      gastroesophageal reflux disease (GERD). This case-control study included cases
      with GERD (n = 142), Barrett esophagus (n = 130), and esophageal adenocarcinoma
      (n = 57). Controls comprised 102 asymptomatic individuals. Using logistic
      regression methods, we compared obesity rates between cases and controls
      adjusting for differences in age, gender, and lifestyle risk factors. Relative to
      normal weight, obese individuals were at increased risk for esophageal
      adenocarcinoma (Odds Ratio [OR] 4.67, 95% Confidence Interval [CI] 1.27-17.9).
      Diets high in vitamin C were associated with a lower risk for GERD (OR 0.40, 95%
      CI 0.19-0.87), Barrett esophagus (OR 0.44, 95% CI 0.20-0.98), and esophageal
      adenocarcinoma (OR 0.21, 95% CI 0.06-0.77). For the more established risk
      factors, we confirmed that smoking was a significant risk factor for esophageal
      adenocarcinoma, and that increased liquor consumption was associated with GERD
      and Barrett esophagus. In light of the current obesity epidemic, esophageal
      adenocarcinoma incidence rates are expected to continue to increase. Successful
      promotion of healthy body weight and diets high in vitamin C may substantially
      reduce the incidence of this disease.

PMID- 16984527
TI  - Histomorphological tumor regression grading of esophageal carcinoma after
      neoadjuvant radiochemotherapy: which score to use?
AB  - Histopathological tumor regression grade (TRG) has been shown to be a prognostic
      factor in patients with esophageal cancer after neoadjuvant radiochemotherapy
      (RCT). The system introduced by Mandard to group TRG (Cancer 1994;73:2680-2686)
      has been used to analyse and discuss its prognostic significance on survival in a
      single institution retrospective analysis: TRG 1 (complete regression) - TRG 5
      (absence of regressive changes). Sixty patients with locally advanced (T3/4 or
      N1) adenocarcinoma or squamous cell carcinoma received cisplatin-based RCT. Three
      to four weeks later operation for curative intent was performed. Median follow-up
      was 17.7 months. Histopathological tumor stages were stage 0 in 17%, stage I in
      10%, stage II in 60%, stage III in 12% and stage IVA in 1%. The 5-year overall
      survival (OS) rate was 35%. In univariate analysis, ypN-status and TRG correlated
      significantly with OS (P = 0.004, P = 0.0008, respectively). While OS of TRG 1
      differed significantly from all other groups, no differences in OS between the
      other TRG groups were seen. Patients with complete tumor regression after
      neoadjuvant RCT showed a much better survival than patients with tumors that
      responded less to induction therapy. Further qualitative subdivision of tumor
      regression could not identify patient groups with significant differences in
      prognosis. After comparing our data with the literature, it is reasonable to
      consider classifying all patients into 'Complete tumor regression' and
      'Incomplete tumor regression'.

PMID- 16984528
TI  - Changes in esophageal motility after porfimer sodium photodynamic therapy for
      Barrett's dysplasia and mucosal carcinoma.
AB  - Esophageal dysmotility is common in patients with Barrett's esophagus. Previously
      we have reported deterioration of esophageal motility after photodynamic therapy
      (PDT) in a heterogeneous group of patients with esophageal carcinoma. This
      prospective study in consecutive patients describes changes in motility noted
      after endoscopic ablation. Forty-seven patients referred to our institution for
      endoscopic ablation for Barrett's high grade dysplasia or mucosal carcinoma
      between August 2001 and May 2003 were prospectively evaluated with esophageal
      manometry before and after porfimer sodium PDT. Six patients did not complete the
      study. Manometry results were classified as normal, diffuse esophageal spasm,
      ineffective esophageal motility, or aperistalsis. Abnormal esophageal motility
      was found in 14 of 47 (30%) patients at study entry ([diffuse esophageal spasm]
      DES-3, [ineffective esophageal motility] IEM-7, Aperistalsis-4). After PDT, 11 of
      41 patients with paired studies experienced a change in manometric diagnosis.
      Three patients had an improvement in motility, seven a worsening and one changed
      diagnosis, but did not particularly worsen or improve. No patient developed new
      aperistalsis. Therefore, abnormal motility was present in 19 of 41 (46%) patients
      after PDT (DES-2, IEM-14, Aperistalsis-3). There was a statistically significant
      (P = 0.016) relationship with longer segment Barrett's esophagus and
      deterioration of function. Baseline abnormalities in motility can occur in
      patients with Barrett's high-grade dysplasia or mucosal carcinoma. Changes in
      esophageal function also may occur following photodynamic therapy, but usually
      are not clinically significant. Worsening in function was more likely to occur in
      patients with longer segment Barrett's esophagus.

PMID- 16984529
TI  - Left thoracoabdominal esophagogastrectomy: still a valid operation for carcinoma
      of the distal esophagus and esophagogastric junction.
AB  - The left thoraco-abdominal (LTA) esophago-gastrectomy is rarely performed and yet
      provides excellent exposure of the esophageal hiatus. The aim of this study was
      to review the outcome of LTA esophago-gastrectomy within a single unit. Patients
      were selected for an LTA esophago-gastrectomy (January 2000 - June 2003) based
      upon the presence of locally advanced tumors of the distal esophagus and cardia.
      These patients were identified from a prospective consultant database. LTA
      esophagogastrectomy was technically possible in all 38 patients (34 males; median
      age = 63 years). In-hospital mortality was 2.6% (1 patient). Four patients
      (10.5%) were admitted to the intensive care unit and three (7.9%) returned to
      theatre. Two patients developed clinically apparent anastomotic leaks (5.3%). A
      potentially curative resection was performed in 34 patients (89%) but 22 (57.8%)
      of these patients were subsequently found to have tumor cells at or within 2 mm
      from the circumferential resection margin. The 1-year and 2-year overall survival
      rates were 70% and 52%, respectively. Long-term complications included benign
      anastomotic stricture (24%), delayed gastric emptying (26%) and a persistent
      thoracic wound sinus (15%). LTA esophagogastrectomy remains a viable approach
      with an acceptably low incidence of short and long-term complications.

PMID- 16984530
TI  - Esophageal cancer after distal gastrectomy.
AB  - The effect of gastrectomy on the subsequent development of esophageal cancer was
      investigated. Duodenogastroesophageal reflux is thought to be common in patients
      after distal gastrectomy, but whether this contributes to the development of
      esophageal cancer in such patients is controversial. We retrospectively evaluated
      153 patients who underwent subtotal esophagectomy for thoracic esophageal cancer
      between January 2002 and July 2005. They were divided into two groups, according
      to whether or not they had previously undergone a gastrectomy: group 1,
      comprising 14 patients who had undergone gastrectomy and group 2, comprising 139
      patients who had not. Clinical profiles of the patients were obtained from the
      medical records and the whole resected esophagus was histopathologically
      examined. The interval between gastrectomy and esophagectomy in group 1 was
      significantly shorter in the patients who had undergone gastrectomy for gastric
      cancer (10.5 +/- 4.2 years) than in those who had undergone gastrectomy for a
      peptic ulcer (28.9 +/- 3.0 years). The interval was also somehow shorter in the
      patients for whom anastomosis had been performed by Billroth I (21.3 +/- 5.6
      years) compared with Billroth II (29.7 +/- 3.2 years), although the difference
      did not reach its statistical significance (P = 0.11). Moreover, the proportion
      of lower third tumors in patients after gastrectomy was significantly higher
      compared with that of the patients with intact stomach. These findings suggest
      that a history of gastrectomy is associated with more lower-third squamous cell
      esophageal carcinoma.

PMID- 16984531
TI  - Cyclooxygenase-2 expression in squamous cell carcinoma of the esophagus.
AB  - Increased cyclooxygenase-2 expression has been reported to be a poor prognostic
      indicator in a number of cancers. In this study we investigated the relationship
      between COX-2 expression in squamous cell carcinoma of the esophagus and tumor
      characteristics and patient survival. The study group consisted of 90 men and 48
      women who underwent esophagectomy for squamous cell carcinoma of the esophagus
      between October 1984 and May 1985. COX-2 expression was measured by
      immunohistochemistry in 138 primary cancers, 23 metastatic lymph nodes and 21
      normal esophageal stumps. The relationship between the extent of staining for COX
      2 and clinicopathological features and survival was determined. The extent of
      staining for COX-2 in both primary and metastatic cancers was higher than in
      normal squamous epithelia (P = 0.002 and P < 0.0001 respectively), and the grade
      of staining in the primary tumor correlated positively with the finding of lymph
      node metastases (P = 0.03). The 5-year survival rate in patients with less than
      10% COX-2 positive cells was 47.5% compared to 23.2% in patients with more than
      10% COX-2 positive cells (P = 0.0036). The relationship between survival and COX
      2 staining was not due to COX-2 being a surrogate marker for TNM stage. Our
      results show that the expression of COX-2 is elevated in squamous cell carcinoma
      of the esophagus compared to normal epithelium and correlates with lymph node
      metastases. Survival was longer in those patients whose tumors expressed lower
      levels of COX-2.

PMID- 16984532
TI  - Immunohistochemical analysis of nuclear survivin expression in esophageal
      squamous cell carcinoma.
AB  - Despite advances in the treatment of esophageal carcinoma, the prognosis for this
      disease remains poor. Therefore, it is important to obtain a better understanding
      of the molecular basis of esophageal carcinogenesis. The purpose of this study
      was to clarify the roles of survivin in esophageal squamous cell carcinoma
      (ESCC). One hundred 22 ESCC surgical specimens resected from 1989 to 1999 were
      examined. Survivin expression was assessed by immunohistochemistry. Tumor cells
      were considered survivin-positive if the immunoreactivity was confined to the
      nucleus, and a scoring method was applied. Survivin-positive immunostaining was
      detected in 68 patients (56%). There was a significant association between
      survivin expression and pN (P = 0.0472). Moreover, the overall survival rate was
      worse in patients with survivin-positive tumors than in patients with survivin
      negative tumors (P = 0.0189). The overexpression of survivin was associated with
      the overall survival rate and poor prognosis in patients with ESCC. Survivin may
      be targeted during cancer therapy because of its selective expression in
      malignant tissue.

PMID- 16984533
TI  - Correlation of gastroesophageal reflux disease symptoms characteristics with long
      segment Barrett's esophagus.
AB  - Thus far, there has been a paucity of studies that have assessed the value of the
      different gastroesophageal reflux disease (GERD) symptom characteristics in
      identifying patients with long-segment Barrett's esophagus versus those with
      short-segment Barrett's esophagus. To determine if any of the symptom
      characteristics of GERD correlates with long-segment Barrett's esophagus versus
      short-segment Barrett's esophagus. Patients seen in our Barrett's clinic were
      prospectively approached and recruited into the study. All patients underwent an
      endoscopy, validated GERD symptoms questionnaire and a personal interview. Of the
      88 Barrett's esophagus patients enrolled into the study, 47 had short-segment
      Barrett's esophagus and 41 long-segment Barrett's esophagus. Patients with short
      segment Barrett's esophagus reported significantly more daily heartburn symptoms
      (84.1%) than patients with long-segment Barrett's esophagus (63.2%, P = 0.02).
      There was a significant difference in reports of severe to very severe dysphagia
      in patients with long-segment Barrett's esophagus versus those with short-segment
      Barrett's esophagus (76.9%vs. 38.1%, P = 0.02). Longer duration in years of chest
      pain was the only symptom characteristic of gastroesophageal reflux disease
      associated with longer lengths of Barrett's mucosa. Reports of severe or very
      severe dysphagia were more common in long-segment Barrett's esophagus patients.
      Only longer duration of chest pain was correlated with longer lengths of
      Barrett's esophagus.

PMID- 16984534
TI  - Esophageal acid exposure at pH < or = 2 is more common in Barrett's esophagus
      patients and is associated with oxidative stress.
AB  - Barrett's esophagus (BE) patients demonstrate a higher distal esophageal acid
      exposure profile than other gastroesophageal reflux disease patients. Cellular
      oxidative stress has been proposed to contribute to the development of BE and
      esophageal adenocarcinoma. However, a relationship between low esophageal pH and
      oxidative stress has yet to be elucidated. The aim of this study was to determine
      the duration of low pH exposure in the esophagus of BE patients compared to those
      with erosive esophagitis (EE) and to test if brief exposure to low pH leads to
      the induction of reactive oxygen species (ROS). Seventy-three patients with BE or
      EE were evaluated by 24-hour esophageal pH monitoring and the percentage of time
      during which there was exposure to pH < or = 4 and pH < or = 2 was recorded. In
      vitro, Seg-1 and Het-1A cells were evaluated after brief exposure to pH4 or pH2
      by flow cytometry and fluorescent microscopy for the production of ROS. BE
      patients demonstrated a significantly higher exposure to low pH values (pH < or =
      2) than EE patients. The mean percent total time, duration and mean number of
      reflux episodes at pH < or = 2 were 2.8 +/- 0.53%, 28.8 +/- 3.6 seconds and 79 +/
      11.4 episodes in BE patients, whereas in EE patients they were significantly
      less, 1.16 +/- 0.3%, 15.6 +/- 1.2 seconds and 48.3 +/- 8.8 episodes, respectively
      (P < 0.05). In vitro experiments indicate that esophageal cells, when exposed to
      pH 2, produce ROS. In vitro studies using brief pH 2 exposure are biologically
      relevant to the clinical situation. Our studies indicate that such exposure
      induces oxidative stress. This stress may cause DNA damage, mutations and
      progression to cancer.

PMID- 16984535
TI  - Gastroesophageal reflux: prevalence of psychopathological disorders and quality
      of life implications.
AB  - There is evidence in the literature that psychosocial aspects affect the symptoms
      and results of surgery for gastroesophageal reflux. The purpose of this study was
      to estimate the prevalence of psychopathological disorders measured using the
      General Health Questionnaire (GHQ-28) in a sample of patients with
      gastroesophageal reflux, and to assess the influence of such disorders on their
      quality of life. A prospective study was conducted in 74 consecutive patients
      before gastroesophageal reflux surgery; patients answered the GHQ-28, the health
      questionnaire SF-36, and the Gastrointestinal Quality of Life Index (GIQLI). The
      convergent validity of the GHQ-28 questionnaire as compared to the other two
      questionnaires and preoperative quality of life was tested. A pathological result
      of the GHQ-28 questionnaire was found in 38.3% of patients. A correlation was
      seen between the results of the GHQ-28 questionnaire and all categories of the SF
      36 and GIQLI questionnaires. Patients with pathological results in the GHQ-28
      questionnaire had poorer results in all dimensions of the SF-36 and GIQLI quality
      of life questionnaires as compared to patients with a normal result in the GHQ-28
      questionnaire. In conclusion, 38.3% of patients with gastroesophageal reflux
      showed psychopathological disorders when administered the GHQ-28 questionnaire.
      These patients also had poorer results in quality of life studies.

PMID- 16984536
TI  - Laryngopharyngeal reflux in patients with symptoms of gastroesophageal reflux
      disease.
AB  - Laryngopharyngeal reflux (LPR) has been extensively studied in patients with
      laryngeal signs and symptoms, gastroesophageal reflux being identified in
      approximately 50%. Few studies have investigated the incidence and significance
      of LPR in GERD patients. Two-hundred and seventy-six consecutive patients
      referred with symptoms of gastroesophageal reflux had dual probe 24 h pH,
      esophageal manometry, GERD and ENT questionnaires. LPR was defined as at least
      three pharyngeal reflux events less than pH 5.0 with corresponding esophageal
      reflux, but excluding meal periods. Fourty-two percent of patients were positive
      for LPR on 24 h pH monitoring and 91.3% corresponded with an abnormal esophageal
      acid score. Distal esophageal acid exposure was significantly greater (P < 0.001)
      in patients with LPR but symptoms of GERD and regurgitation scores showed no
      significant differences between patients with positive and negative LPR on 24 h
      pH. There was no significant difference between the incidence of LPR in patients
      with or without laryngeal symptoms. There is a high incidence of LPR in patients
      with GERD but its significance for laryngeal symptoms is tenuous. Fixed distance
      dual probe pH monitoring allows documentation of conventional esophageal reflux
      and LPR.

PMID- 16984537
TI  - Multichannel intraluminal impedance for the assessment of post-fundoplication
      dysphagia.
AB  - Dysphagia often occurs after fundoplication, although its pathophysiology is not
      clear. We sought to better understand postfundoplication dysphagia by measuring
      esophageal clearance with multichannel intraluminal impedance (MII) along with
      more traditional work-up (manometry, upper gastrointestinal imaging [UGI],
      endoscopy). We evaluated 80 consecutive patients after laparoscopic
      fundoplication between April 2002 and November 2004. Patients were evaluated
      clinically and underwent simultaneous manometry and MII, 24-hour pH monitoring,
      endoscopy, and UGI. For analysis, patients were divided into the following groups
      based on the presence of dysphagia and fundoplication anatomy (by UGI/endoscopy):
      (1) Dysphagia and normal anatomy; (2) Dysphagia and abnormal anatomy; (3) No
      dysphagia and abnormal anatomy; and (4) No dysphagia and normal anatomy. Patients
      with dysphagia (Groups 1 & 2) had similar peristalsis (manometry), but were more
      likely to have impaired clearance by MII (32 pts, 62%) than those without
      dysphagia (9 pts, 32%, P = 0.01). Patients with abnormal anatomy (Groups 2 & 3)
      were also more likely to have impaired esophageal clearance (66%vs. 38%, P =
      0.01). Finally, of patients that had normal fundoplication anatomy, those with
      dysphagia were much more likely to have impaired clearance (12 pts, 52%) than
      those with dysphagia (4 pts, 21%, P = 0.03). MII after fundoplication provides
      objective evidence of esophageal clearance, and is commonly abnormal in patients
      with abnormal fundoplication anatomy and/or dysphagia. Esophageal clearance is
      impaired in the majority of patients with postoperative dysphagia, even with
      normal fundoplication anatomy and normal peristalsis. MII may detect disorders in
      esophageal motility not detected by manometry.

PMID- 16984538
TI  - Management of achalasia with transabdominal esophagocardiomyotomy and partial
      posterior fundoplication.
AB  - In this article we present our experience in the management of achalasia. From
      May 1988 through August 2005, 71 patients with achalasia underwent transabdominal
      esophagocardiomyotomy and partial posterior fundoplication. Barium swallow,
      manometry, and 24-h pH studies were performed in all patients preoperatively.
      Manometry and 24-h pH monitoring were only carried out in 58 patients at the
      third post-operative week and in 43 patients during follow-up, even though 52
      patients were included in the follow-up. There were no operative deaths or
      complications. All the 71 patients were able to eat semifluid or solid food
      without dysphagia and heartburn at discharge. Esophageal barium studies showed
      that the maximum esophageal diameter decreased 2.2 cm and the minimum
      gastroesophageal junction diameter increased 8.4 mm after operation. Manometry
      examination in 58 patients revealed that the lower esophageal sphincter resting
      pressure decreased 15.0 mmHg in the wake of the procedure. Twenty-four hour pH
      monitoring demonstrated that reflux events were within the normal post-operative
      range. Fifty-five of the 58 patients had normal DeMeester scores. Among the
      patients with a mean 90-month follow-up, 49 patients had normal intake of food
      without reflux, the remaining three had mild dysphagia without requiring
      treatment. All the patients resumed their preoperative work and social
      activities. The manometry and 24-h pH studies in the 43 patients showed there
      were no significant changes between the third post-operative week and during
      follow-up. Transabdominal esophagocardiomyotomy and posterior partial
      fundoplication are able to relieve the functional outflow obstruction of the
      lower esophageal sphincter, obviate the rehealing of the myotomy edge and prevent
      gastroesophageal reflux in patients who have undergone myotomy alone.

PMID- 16984539
TI  - Radionuclide imaging for the assessment of esophageal motility disorders in mixed
      connective tissue disease patients: relation to pulmonary impairment.
AB  - Esophageal functional abnormalities may lead to regurgitation, chronic
      esophagitis and life-threatening conditions such as aspiration pneumonia. In
      mixed connective tissue disease patients, previous reports showed that esophageal
      dysfunction varies according to the method employed for investigation. Our study
      was conceived to: (i) assess esophageal motility and mucosal aspects in patients
      with mixed connective tissue disease by endoscopy, cine-esophogram and
      scintigraphy focusing on the prevalence of each exam; and (ii) verify the
      association between pulmonary and esophageal dysfunctions. Twenty-four mixed
      connective tissue disease patients were enrolled for this study. Cine-esophogram
      and upper digestive endoscopy with mucosal biopsy were performed according to
      previous standardization. Radionuclide esophageal scintigraphy was performed with
      a semisolid meal with (99m)Tc. Eleven healthy individuals voluntarily submitted
      to scintigraphy as controls. Cine-esophogram showed esophageal delayed emptying
      in 90% of patients. At scintigraphy there was a significant delay in total
      esophageal transit time in the group of patients when compared to healthy
      controls (35.3 +/- 8.2 s. vs. 13.6 +/- 9.5 s.; P < 0.0001). The whole esophageal
      body showed dysmotility in 96% of patients. The cine-esophogram detected
      functional esophageal impairment similar to scintigraphic findings.
      Histopathologic examination found esophagitis in 95% of studied patients. Reduced
      lung volumes were associated with esophagitis and delayed esophageal clearance at
      scintigraphy, observed at the distal portion of the esophagus. Esophageal
      scintigraphy is easy to perform, with good acceptance by patients with low
      radiation exposition. It is a useful non-invasive test for follow-up and
      interventional studies concerning esophagus dysfunction.

PMID- 16984540
TI  - Differences in response of the proximal esophagus to wet swallows in patients of
      Chagas' disease and idiopathic achalasia.
AB  - Chagas' disease and idiopathic achalasia have similar esophageal manifestations
      such as absent or incomplete lower esophageal sphincter relaxation and
      aperistalsis in the esophageal body (alterations seen mainly in the distal
      esophageal body). Our aim in this paper was to study the response of the proximal
      esophageal body to wet swallows in patients with Chagas' disease and patients
      with idiopathic achalasia. We retrospectively analyzed the time interval between
      the onset of the pharyngeal contractions 1 cm proximal to the upper esophageal
      sphincter, as well as 5 cm distal to the pharyngeal measurement. Amplitude,
      duration and area under the curve of contractions in the proximal esophagus were
      also determined in 42 patients with Chagas' disease (15 with associated
      esophageal dilatation), 21 patients with idiopathic achalasia (14 with
      concomitant esophageal dilatation) and 31 control subjects. The time between the
      onset of pharyngeal and proximal esophageal contractions was longer in patients
      with Chagas' disease and in those with esophageal dilatation (1.39 +/- 0.16 s)
      than in control subjects (0.86 +/- 0.04 s, P < 0.01). The amplitude of proximal
      esophageal contractions was lower in patients with idiopathic achalasia and
      esophageal dilatation (60.9 +/- 16.3 mmHg) than in control subjects (89.7 +/- 6.9
      mmHg, P = 0.06). The authors conclude that in patients with advanced esophageal
      disease, the proximal esophageal contractions in Chagas' disease have a delayed
      response to wet swallows when compared with controls, and that the amplitude of
      proximal esophageal contractions was lower than expected in patients with
      idiopathic achalasia.

PMID- 16984541
TI  - Vagal integrity in vagal-sparing esophagectomy: a cadaveric study.
AB  - Esophagectomy is associated with a significant number of complications, some of
      them related to the concomitant vagotomy. The vagal-sparing esophagectomy is an
      attractive alternative to the conventional procedure; however, few clinical
      series have attested the integrity of the vagi nerves after esophagectomy. The
      surgical anatomy of the vagus in the mediastinum has received little interest as
      well. The anatomy of the vagus was studied in 30 fresh cadavers. Twenty cadavers
      were submitted to a vagal-sparing esophagectomy, and after the procedure,
      anatomical vagal integrity was evaluated. Concerning the anatomy of the vagus,
      one or more vagal trunks were present in all cases. Four patterns were
      identified: Type I, two distinct trunks without communicating branches, present
      in eight (26.7%) cases; Type II, two distinct trunks with communicating branches,
      present in 17 (56.7%) cases; Type III, one or more bifurcated trunks, present in
      four (13.3%) cases; and Type IV, crossing trunks, present in one (3.3%) case.
      Regarding the esophagectomy, operative accidents were not noticed; in five cases,
      there was incomplete removal of the muscular layer of the esophagus. In all cases
      vagi nerves were preserved. The vagus is preserved in a cadaveric model of the
      vagal sparing esophagectomy, irrespective of the anatomy of the vagus in the
      mediastinum.

PMID- 16984542
TI  - Electroincision of refractory esophagogastric anastomotic strictures.
AB  - Most esophagogastric anastomotic strictures can be successfully managed with
      endoscopic dilation. However, strictures that do not respond to repeated dilation
      (refractory strictures) are difficult to manage. We report a series of nine
      patients treated with needle-knife electroincision of symptomatic esophagogastric
      anastomotic strictures refractory to balloon or Savary dilation. Prior to needle
      knife electroincision, the median symptom-free interval between dilations was 13
      days; median number of dilations was six (range 3-12). After electroincision, 8/9
      patients have experienced a reduction in dysphagia symptoms and a reduced need
      for endoscopic dilations (follow-up: 90-420 days). No complications occurred.
      Needle-knife stricturoplasty of refractory esophagogastric anastomotic strictures
      may produce improved clinical results and may delay or eliminate dysphagia
      recurrence.

PMID- 16984544
TI  - Joaquin Maria Albarran Y Dominguez: microbiologist, histologist, and urologist--a
      lifetime from orphan in Cuba to Nobel nominee.
AB  - Joaquin Albarran was an extraordinary late 19th century urologist. His early
      career was in the field of microbiology and histopathology in Paris at a time of
      great medical developments and innovations. His later contributions to urology
      included the Albarran lever, Albarrans sign, Albarran-Ormond syndrome and seminal
      works on testicular and renal tumors. He also wrote treatizes on the
      pathophysiology of acute urinary retention, nephritis and calculus ureteric
      obstruction. He died at the young age of 52 from the effects of tuberculosis and
      in this same year was nominated for the Nobel prize in medicine.

PMID- 16984545
TI  - Our experience in eight cases with urinary hydatid disease: a series of 372 cases
      held in nine different clinics.
AB  - OBJECTIVES: Hydatid disease, a parasitic infestation caused by the larval stage
      of the cestode Echinococcus granulosus, is diagnosed commonly in the east and
      south-east regions of Turkey. The aim of this study is to emphasize the
      relatively frequent occurrences of echinococcosis in our region, and to discuss
      therapeutic options and treatment results according to current literature.
      METHODS: A retrospective 10-year review of nine different clinics' records of the
      Research Hospital of the Medical School of Yuzuncu Yil University revealed 372
      hydatid disease cases that were localized in various organs and treated
      surgically (271 cases) or drained percutaneously (99 cases). Hydatid disease was
      diagnosed by ultrasonography (US) and computed tomography scans (CT) and
      confirmed histopathologically. RESULTS: The involved organ was lung in 203 cases
      (131 adults, 72 children), liver in 150, spleen in 9, brain in 2, kidneys in 7
      cases and the retrovesical area in 1 case. The urogenital system is involved at a
      rate of 2.15%. Two hundred and seventy-one cases were treated surgically and 99
      percutaneously. Two cases with renal hydatid cyst refused the surgical procedure
      (one had a solitary kidney with hydatid cyst). Albendazole was administered to
      192 patients; 93 patients had open surgical procedure and 99 patients underwent
      percutaneous procedure. Cysts were excised totally in the open surgical
      procedure; however, involved kidneys were removed totally (four cases) except
      one. Cystectomy and omentoplasty was performed in one case. Complications were as
      follows: in six cases, cystic material was spilled into the bronchial cavity
      during the dissection and a renal hydatid cyst ruptured and spilled
      retroperitoneally. CONCLUSION: Hydatid disease is a serious health problem in
      Turkey. The mainly affected organs are liver and lung. It can be treated surgical
      or by percutaneous aspiration.

PMID- 16984546
TI  - Retroperitoneal dismembered pyeloplasty: initial experiences.
AB  - AIM: To review the results of our first 40 cases of retroperitoneal dismembered
      pyeloplasty and to compare them with series of open and other minimally invasive
      treatments of pelviureteric junction (PUJ) obstruction. Also to compare our first
      20 cases with the second 20 cases to see if there was an improvement in results
      with experience. METHODS: A retrospective review of the first 40 laparoscopic
      pyeloplasties performed by a single lead surgeon at two institutions was
      performed. The diagnosis of PUJ obstruction was confirmed with an intravenous
      urogram as well as a renogram prior to surgery. A retroperitoneal, dismembered
      pyeloplasty was routinely performed with three or four ports. All patients were
      followed up with an intravenous urogram, renogram and review of symptoms at 4
      months and annual renogram after that. RESULTS: Average operation time was 236
      min and this appeared to decrease with experience. Two cases had to be converted
      to open operations. The mean hospital stay was 3.4 days. Out of the 40 patients,
      34 have had successful laparoscopic operations with total symptomatic relief as
      well as radiologically proven deobstruction. There were four major complications
      with 3 patients going on to have redo open pyeloplasty operations. There were
      seven minor complications. CONCLUSIONS: In our experience, retroperitoneal
      dismembered pyeloplasty is an effective and safe means of treating PUJ
      obstruction. Our results seem to be comparable with series of open pyeloplasty
      and other laparoscopic series and are better than some other minimally invasive
      techniques.

PMID- 16984547
TI  - Retroperitoneoscopic pyeloplasty: using reconstructive methods based on
      intraoperative findings.
AB  - AIM: Reconstructive laparoscopic procedures have been recognized as a less
      invasive treatment than conventional open procedures. However, although the
      laparoscopic pyeloplasty has also been accepted as useful, few findings have been
      reported relevant to the retroperitoneal approach. To elucidate its effectiveness
      and safety, laparoscopic surgery via the retroperitoneal approach was examined in
      our institution. Furthermore, the importance of laparoscopic observation for
      ureteropelvic junction and urine passage ureteropelvic junction without
      indwelling ureteral stent. METHODS: Between July 1998 and December 2004, 13 men
      and 15 women underwent laparoscopic retroperitoneal surgery for ureteropelvic
      junction obstruction. The mean patient age was 33.6 years (range: 13-70 years).
      Methods of repair were determined by intraoperative findings for the relationship
      between the ureteropelvic junction and surrounding vessels. An indwelling
      ureteral stent was removed before initiating laparoscopic operation to observe
      the relationship between ureteropelvic junction and aberrant vessels more
      precisely. RESULTS: An aberrant renal vessel was found in 13 patients (46%).
      Dismembered pyeloplasty was carried out in 21 patients, Y-V plasty in five
      patients and Hellstrom technique in two patients. Ureteral transposition was not
      required in dismembered pyeloplasty cases. All patients achieved
      retroperitoneoscopic pyeloplasty without open conversion. The mean operative time
      was 272 min (range: 155-490 min). The mean estimated blood loss was 44 mL (range:
      10-200 mL). No major complications were observed during the intraoperative
      period, but urinary tract infection occurred in two patients in the postoperative
      period. In all patients except one, obstruction was improved or resolved.
      CONCLUSIONS: Laparoscopic retroperitoneal surgery is not only able to repair
      ureteropelvic junction obstruction, but can also be done safety and less
      invasively. We believe that laparoscopic observation without indwelling stent
      will contribute to a more appropriate choice of pyeloplasty.

PMID- 16984548
TI  - Experience and functional outcome of modified ileal neobladder in 95 patients.
AB  - AIMS: We took advantage of the Goodwin method to develop a modified ileal
      neobladder. We present the operation procedure and assessed the functional
      results. METHODS: From April 1997 and May 2005, 95 patients (75 men and 20
      women), mean age 64.6 years (range: 36-80 years) underwent orthotopic ileal
      neobladder replacement with application of the Goodwin method. The Le Duc
      technique was used for antireflux procedure. However, for the last 35 patients,
      antireflux procedure was not carried out. The median follow-up period was 37
      months (range: 3-98 months). We reviewed the surgical outcome and complications.
      Continent status and urodynamic profile were also measured. RESULTS: The mean
      operation time for the neobladder formation was 130 mins (range: 65-285 mins).
      There were no perioperative deaths. Leakage from the ileourethral anastomosis
      leak was found in four patients (4.2%), wound infection in nine patients (9.5%),
      ileal anastomosis leak in two patients (2.1%) and paralytic ileus in two
      patients. No hydronephrosis, neobladder-ureteral reflux or deterioration of renal
      function was seen. The maximum neobladder pressure was 21 +/- 13 cm (mean +/- SD)
      at 6 months and 12 +/- 11 cm at 12 months after surgery. The neobladder capacity
      was 293 +/- 118 mL at 6 months and 312 +/- 85 mL at 12 months after surgery. Of
      the 95 patients, 87 (91.6%) maintained complete dryness day and night.
      CONCLUSIONS: These results suggest that the present orthotopic ileal neobladder
      is simple to be carried out and achieves acceptable voiding function. Longer
      observation for neobladder and upper urinary tract function is necessary.

PMID- 16984549
TI  - Selenium is inversely associated with bladder cancer risk: a report from the
      Belgian case-control study on bladder cancer.
AB  - AIM: Selenium is an essential trace element with suspected anticarcinogenic
      properties in humans. To date, eight epidemiological studies have examined the
      association between serum selenium concentration and bladder cancer risk.
      METHODS: The authors carried out a population case-control study in 178 cases and
      362 controls to assess the relationship between bladder cancer risk and selenium
      serum concentrations. Unconditional logistic regression was calculated to
      determine odds ratios (OR) for bladder cancer occurrence with corresponding 95%
      confidence intervals (95% CI). Effect modification by smoking status, low fruit
      and vegetable intake, retinol equivalent, vitamin C, vitamin E and total
      antioxidant status were also assessed. RESULTS: Serum selenium level was
      negatively associated with bladder cancer risk. After adjustment for sex, age,
      smoking and occupational exposure, the OR was 0.48 (95% CI 0.29-0.79) comparing
      the second with the lowest tertile (serum selenium concentration >82.40
      microg/L). The adjusted OR for the highest tertile (serum selenium concentration
      >96.00 microg/L), was 0.30 (95% CI 0.17-0.52) (P-trend <0.001). An increase of 10
      microg/L in serum selenium concentration was associated with a significant
      decreased bladder cancer risk (OR: 0.76; 95% CI 0.67-0.85). CONCLUSION: This case
      control study suggests an inverse association between serum selenium
      concentration and bladder cancer risk.

PMID- 16984550
TI  - General versus spinal anesthesia with different forms of sedation in patients
      undergoing radical retropubic prostatectomy: results of a prospective, randomized
      study.
AB  - AIM: To assess the impact of spinal anesthesia (SpA) combined with three
      different forms of conscious sedation on intraoperative and postoperative outcome
      in patients undergoing radical retropubic prostatectomy (RRP) for organ confined
      prostate cancer (pCa). METHODS: A total of 121 consecutive patients with pCa
      undergoing RRP were randomized into four groups. They were randomized as follows:
      group 1 (general anesthesia: 34 patients), group 2 (lumbar 2 to lumbar 3
      interspace SpA with diazepam as sedative agent: 28), group 3 (SpA with propofol:
      30), and group 4 (SpA with midazolam: 29). Intraoperative and perioperative
      parameters were collected. RESULTS: The present study showed that muscle
      relaxation throughout RRP was not different in the four groups; bleeding was
      significantly (P = 0.04) lower with SpA, regardless of the form of sedation.
      Group 3 patients reported the best postoperative oxygen saturation percentage by
      pulse oximetry and sedation score (P = 0.02; d.f. = 3 and P < 0.0001; d.f. = 3,
      respectively), the shortest waiting time in the postoperative holding area (P <
      0.001; d.f. = 3), the lowest pain on postoperative day 1 (P = 0.0004; d.f. = 3),
      and the highest frequency of first flatus passage (P = 0.0001; d.f. = 3). A
      higher number of group 4 patients were able to carry out unassisted ambulation (P
      < 0.0001; d.f. = 3). CONCLUSIONS: Conscious sedation coupled with SpA is a safe,
      reliable and effective procedure for patients undergoing RRP. The use of propofol
      as sedative agent offers several advantages both over other types of conscious
      sedation and general anesthesia.

PMID- 16984551
TI  - Relevance of postcatheter removal incontinence to postoperative urinary function
      after radical prostatectomy.
AB  - AIM: We examined whether postoperative urinary function after radical
      prostatectomy is associated with immediate incontinence just after catheter
      removal. PATIENTS AND METHODS: The current study included 80 patients with
      clinically localized prostate cancer, who underwent radical retropubic
      prostatectomy between January 2002 and May 2004. The amount of immediate
      incontinence was measured with a 24-h pad test just after catheter removal. The
      patients were categorized into the three groups based on the stratified grade of
      immediate urinary incontinence: groups I (0 g; 47 patients), II (1-99 g; 23
      patients) and III (100 g and above; 10 patients), respectively. Urinary function
      and bother were assessed by a self-administered questionnaire using the
      University of California Los Angeles, Prostate Cancer Index at baseline, and at
      3, 6 and 12 months postoperatively. The differences in scores of urinary
      function, bother and clinicopathological parameters were assessed in the three
      groups with one-way analysis of variance. RESULTS: No significant difference was
      observed in the clinicopathological parameters in the three groups.
      Preoperatively significant difference of urinary function scores was not evident
      and that of urinary bother scores was not observed in the three groups.
      Postoperatively urinary function scores were significantly different throughout
      the postoperative periods investigated, whereas difference in urinary bother
      scores observed at 3 months tended to disappear with time. CONCLUSION:
      Postcatheter removal incontinence might be related to postoperative urinary
      function after radical prostatectomy, although further investigation is necessary
      regarding the criteria for categorization because of a small number of the
      patients.

PMID- 16984552
TI  - Pretreatment serum level of HER2/nue as a prognostic factor in metastatic
      prostate cancer patients about to undergo endocrine therapy.
AB  - BACKGROUND: Overexpression of the HER2 receptor protein and amplification of the
      HER2 gene has been implicated in tumor development and progression, and has been
      associated with a poor prognosis in several types of cancer. The aim of this
      study was to evaluate whether pretreatment serum HER2 levels can be used to
      predict biochemical recurrence-free survival in prostate cancer patients about to
      undergo endocrine therapy. METHODS: The study population consisted of 379
      untreated patients with histologically diagnosed prostate cancer: 197 with
      T2N0M0, 93 with T3N0M0, 19 with TxN1Mx, and 70 with TxNxM1. Serum HER2 levels
      were assessed in the prostate cancer patients prior to treatment as well as in a
      control group of 100 patients with histologically confirmed non-cancer.
      Biochemical recurrence-free curves for the patients were investigated separately
      using the Kaplan-Meier method. RESULTS: The mean level of HER2 in serum was
      significantly higher in prostate cancer patients than non-prostate cancer
      patients (P = 0.006). Also, the serum HER2 level was significantly higher in bone
      metastatic cancer patients (14.3 +/- 6.3 ng/mL) than in non-metastatic patients
      (T2: 11.9 +/- 2.3 ng/mL, P = 0.003; T3: 12.2 +/- 2.8 ng/mL, P = 0.011). The
      metastatic patients were divided into those with low and high HER2 levels using a
      cutoff value of 12.6 ng/mL based on receiver-operating characteristic curves. The
      biochemical recurrence-free rate was significantly poorer in patients with a high
      HER2 level (P = 0.0078, log-rank test). Multivariate Cox logistic regression
      analysis demonstrated that the pretreatment serum HER2 value (P = 0.022), serum
      prostate-specific antigen value (P = 0.018), and extent of disease score (P =
      0.027) were independent predictors of recurrence. CONCLUSIONS: The pretreatment
      serum HER2 level may be a useful independent prognostic factor that is associated
      with a high risk of biochemical recurrence in metastatic prostate cancer patients
      about to undergo endocrine therapy.

PMID- 16984553
TI  - Clinical impact of tamsulosin on generic and symptom-specific quality of life for
      benign prostatic hyperplasia patients: using international prostate symptom score
      and Rand Medical Outcomes Study 36-item Health Survey.
AB  - AIM: To examine the efficiency of alpha1-blocker treatment on disease-specific
      and generic quality of life (QOL) in men with clinically diagnosed benign
      prostatic hyperplasia (BPH), the improvement of QOL scores with International
      prostate symptom score (I-PSS) and Rand Medical Outcomes Study 36-item Health
      Survey (SF-36) was prospectively analyzed. METHODS: A total of 68 newly diagnosed
      patients with symptomatic BPH that satisfied all inclusion and none of the
      exclusion criteria were prospectively recruited. All patients received 0.2 mg/day
      of tamsulosin for 12 weeks. All patients underwent pretreatment documentation of
      lower urinary tract symptoms (LUTS) and assessment of symptom-specific QOL.
      Symptoms and general health-related QOL (HRQOL) were assessed using the I-PSS and
      SF-36, respectively. Also, other objective variables, such as prostate volume,
      maximal urinary flow and postvoid residual urine volume, were evaluated. RESULTS:
      After 12 weeks, decrease in I-PSS was 27% compared with baseline (from 16.4 +/-
      7.18 to 11.9 +/- 7.56). All questionnaires in the I-PSS showed improvement after
      tamsulosin treatment and the I-PSS QOL score was improved from 4.51 +/- 1.14 to
      3.17 +/- 1.38 (P < 0.0001) at 12 weeks after tamsulosin administration. In
      intragroup comparisons of HRQOL scores with age-gender adjusted SF-36 Japanese
      national norms, three SF-36 subscales (bodily pain, BP; social function, SF; and
      mental health, MH) were worse in the BPH group aged over 70 years, while younger
      BPH groups aged <70 had better mean SF-36 physical function (PF) scores compared
      with age-gender adjusted Japanese national norms. In the BPH group with a
      prostatic volume > or =20 mL, three mean SF-36 scales (BP, SF and MH) were
      significantly improved after tamsulosin treatment. It is noteworthy that these SF
      36 subscales were identical to those observed to worsen in the older BPH group
      compared to Japanese national norms. CONCLUSIONS: Treatment with tamsulosin for
      symptomatic BPH patients is associated with significant improvement in the
      generic HRQOL, in addition to disease-specific QOL and symptoms, at 3 months
      after drug administration. In particularly, for generic HRQOL with SF-36,
      tamsulosin treatment can efficiently improve three mean SF-36 subscales (BP, SF
      and MH) that are decreased in older BPH patients.

PMID- 16984554
TI  - Comparison of bone-anchored male sling and collagen implant for the treatment of
      male incontinence.
AB  - AIM: To compare the effectiveness of transurethral collagen injection and
      perineal bone-anchored male sling for the treatment of male stress urinary
      incontinence (SUI). METHODS: Seventy-one men with SUI underwent either
      transurethral collagen injections (n = 34) or perineal bone-anchored male sling
      (n = 37) between June 1999 and October 2003. Most of the patients in each group
      had radical retropubic prostatectomy and/or external beam radiation therapy
      (EBRT) in relation to the cause of incontinence. There was one patient in both
      groups who only had EBRT for the cause. The mean duration of incontinence were
      4.2 and 4.4 years, respectively. Collagen injections were carried out
      transurethrally either under regional or general anesthesia until co-aptation of
      mucosa was observed. The male sling was placed under spinal anesthesia with a
      bone drill using either absorbable or synthetic materials. Retrospectively, all
      patients were assessed for continence status and procedure-related morbidity, if
      present. The outcome of both procedures was also compared with the degree of
      incontinence. RESULTS: Ten (30%) patients in the collagen group showed either
      significant improvement or were cured following injections. Preoperatively, the
      mean pad use in collagen group was 4.5 (SD 2.8) per day, whereas it was 2.2 (SD
      1.1) after the injection(s). Collagen injection failed in 24 (70%) of the
      patients. Patients who received the male sling had a mean preoperative pad use of
      3.7 (SD 1.5) and postoperatively, the number decreased to 1.6 (SD 1.2). Most of
      the patients in this group were either totally dry or significantly improved (n:
      28, 76%). There was a statistically significant difference between two groups in
      respect to success rate (P < 0.05). Analysis of treatment outcome with the degree
      of incontinence revealed that the male sling is most effective in patients with
      minimal-to-moderate incontinence. CONCLUSIONS: Our results suggest that the male
      sling, a minimally invasive procedure, is more effective than collagen implant in
      the treatment of mild-to-moderate SUI in men.

PMID- 16984555
TI  - Lack of association between the incidence of testicular germ cell tumors and Y
      chromosome haplogroups in the Japanese population.
AB  - BACKGROUND: Despite being relatively uncommon, testicular germ cell tumors (TGCT)
      are the most common malignant disease in young men. Epidemiological studies
      concerning patients with testicular cancer indicate that the most of them have
      poor semen quality or testicular dysgenesis. However, many studies have shown
      that the Y chromosome harbors many candidate genes responsible for
      spermatogenesis process and development and maintenance of the germ cells. The Y
      chromosome is thought to have a relationship with the formation and progression
      of TGCT. MATERIALS AND METHODS: To verify this relationship, we investigated if
      there is any correlation between the Y chromosome structural variations presented
      as different haplogroups and the occurrence of TGCT in the Japanese population.
      Using combined haplogroups based on typing of three Y chromosome polymorphic
      binary markers, we analyzed 68 TGCT derived from Japanese patients together with
      randomly selected 104 unrelated healthy Japanese matched male controls who were
      confirmed as residents of the same geographic area. RESULTS: Our findings showed
      a lack of association between the incidence of TGCT and the different Y-
      chromosome haplogroups in Japanese population. CONCLUSION: We concluded that
      there are no significant variations in males from different Y chromosome lineages
      regarding their susceptibility or resistance for developing TGCT. The previously
      hypothesized role of the Y chromosome in the development of TGCT is still
      uncertain and needs further verification.

PMID- 16984556
TI  - Management of urethral lesions in penile blunt trauma.
AB  - BACKGROUND: Traumatic lesions to the penis may extend into the corpus spongiosum,
      causing laceration or complete transection of the urethra. Blunt penile trauma is
      usually related to sexual intercourse or manipulation. The aim of this paper was
      to report the authors experience with the management of urethral injuries in
      patients with penile blunt trauma. METHODS: The charts from 77 patients with
      penile blunt trauma were retrospectively reviewed, and the cases associated with
      urethral injuries associated were selected. Patient age ranged from 18 to 63
      years (mean 33 years). RESULTS: From 77 cases assessed, 11 (14.2%) patients had
      urethral injury, 62 (80.5%) had injury of the corpora cavernosa and four (5.2%)
      had injury of the dorsal vein. The etiology of urethral injuries was sexual
      intercourse in 10 patients (91%) and direct trauma to the flaccid penis in one
      patient (9%). A partial urethral disruption was presented in eight patients
      (72.8%) and a total disruption in three patients (27.2%). Preoperative
      urethrogram was performed in seven patients with a suspicion of urethral trauma.
      When a partial injury was present the urethra was closed over the catheter, and
      in the presence of a total injury an end-to-end anastomosis was performed.
      CONCLUSION: The data support the reported incidence of urethral injury associated
      with blunt penile trauma. No clinically apparent urethral structures were
      appreciated with primary urethral repair after a follow up of more than 6 months.

PMID- 16984557
TI  - Down-regulation of Hsp27 radiosensitizes human prostate cancer cells.
AB  - AIM: In this study, we examined whether human Hsp27 is involved in the radiation
      sensitization induced by gamma radiation in cultured human prostate cancer cells.
      METHODS: We transfected DU145 cells with full length Hsp27 antisense cDNA to
      obtain viable cell lines which expressed reduced Hsp27. Selected individual
      clones were subjected to western blot analyses to confirm reduced expression of
      Hsp27. RESULTS: Hsp27 belongs to a family of abundant and ubiquitous stress
      proteins, the small heat shock proteins. It has been shown that Hsp27 can inhibit
      apoptosis both in a caspase-dependent and independent manner. Colony assays
      showed that the cells engineered to express reduced Hsp27 levels had a
      significantly increased sensitivity to gamma radiation compared with control
      cells that were transfected with the vector alone. However, there was also a
      significant difference in viability of cells with reduced Hsp27 levels and
      control cells 72 h after gamma-irradiation. CONCLUSIONS: Our results suggest the
      possible application of antisense Hsp27 cDNA or other methods to reduce Hsp27
      expression as a radiation sensitizer in radiation oncology.

PMID- 16984558
TI  - Decreased expression of G protein-coupled receptor kinases in the detrusor smooth
      muscle of human urinary bladder with outlet obstruction.
AB  - AIM: We examine the expression of mRNA of G protein-coupled receptor kinase (GRK)
      subtypes and muscarinic acetylcholine receptor (M) subtypes in the detrusor
      smooth muscle of the human urinary bladder. Furthermore, we confirm the presence
      and the localization of GRK proteins in the detrusor smooth muscle of the
      obstructed bladder in comparison with the control bladder. METHODS: Detrusor
      smooth muscle tissues of the human urinary bladder were obtained from 12 male
      patients; 6 patients did not have bladder outlet obstruction, and the other 6
      patients had bladder outlet obstruction. Portions of the dome or anterior wall of
      the urinary bladder were used for the present study. Reverse
      transcription/polymerase chain reaction for GRK2, M2 and M3 was performed using
      total RNA extracted from human urinary bladder detrusor. Antibodies to GRK2, GRK3
      and GRK4 were used to confirm the presence of the protein product in the human
      urinary bladder using immunohistochemical staining and the western blotting
      technique. RESULTS: All complementary DNA (cDNA) transcribed from three different
      mRNA (M2, M3 and GRK2) were successfully amplified and size-fractionated. The
      expression of GRK2 protein was strong in the human bladder detrusor, but was
      significantly weakened by western blotting in obstructed bladder in comparison
      with control bladder. CONCLUSIONS: Failure in desensitization mechanisms of
      muscarinic acetylcholine receptors might be related to storage symptom elicited
      by overactivity in obstructed bladder with benign prostatic hyperplasia.

PMID- 16984559
TI  - Adrenocortical carcinoma with tumor thrombus in the right hepatic vein.
AB  - Adrenocortical carcinoma is an unusual neoplasm with very poor prognosis.
      Patients present with an abdominal mass often exceeding 5 cm or as a functional
      tumor. Computed tomography is effective to demonstrate the neoplasm as an
      inhomogeneous adrenal lesion with irregular margins, and magnetic resonance
      imaging is helpful to visualize invasion into large vessels as well. Reported
      herein is a case of large adrenocortical carcinoma with tumor thrombus extending
      into the right hepatic vein.

PMID- 16984560
TI  - Concurrent occurrence of three primary neoplasms with different hystotype in the
      same kidney, associated with an adenoma of the omolateral adrenal gland: first
      case report.
AB  - We present an unusual case of concurrent occurrence of three synchronous primary
      tumors in the same kidney (oncocytoma, chromophobe renal cell carcinoma,
      angiomyolipoma) associated to an adenoma of the omolateral adrenal gland in a
      patient with no evident clinical symptoms. The immunohistochemistry showed a
      positivity for KIT in oncocytoma and chromophobe cell carcinoma, and a weak
      positivity in the angiomyolipoma, only in the cells positive for HMB-45. This is
      the first report of this kind of presentation.

PMID- 16984561
TI  - Monotypic epithelioid angiomyolipoma of the kidney: a case report.
AB  - A case of monotypic variant of epithelioid angiomyolipoma (AML) observed in a 62
      year old woman is reported. The patient complained of abdominal fullness caused
      by a huge left renal mass without evidence of tuberous sclerosis complex. Imaging
      studies showed a left renal mass with an area showing hemorrhage and necrosis.
      The left renal mass, spleen and pancreatic tail were removed en bloc
      transabdominally. The resected tumor weighed 1200 g and showed focal necrosis and
      hemorrhage. Microscopically, the tumor was composed exclusively of atypical
      polygonal cells with copious eosinophilic cytoplasm, pleomorphic nuclei and
      prominent nucleoli. Tumor cells were considered to derive from perivascular
      epithelioid cells, and exhibited strong positive staining for HMB-45 and c-KIT,
      but were negative for epithelial, smooth muscle, and neural markers. As this
      tumor had none of the typical elements of classic AML, the final pathological
      diagnosis was monotypic epithelioid AML.

PMID- 16984562
TI  - Intrarenal arterial stenosis in a patient with thromboangiitis obliterans.
AB  - Thromboangiitis obliterans (TAO) or Buerger's disease is a clinical syndrome
      characterized by the development of segmental thrombotic occlusions of the medium
      and small arteries of the extremities. Exception of the peripheral arteries of
      the extremities in TAO is very rare. Reported herein is the first case of
      intrarenal branch involvement of the renal artery due to TAO.

PMID- 16984563
TI  - Primary gastrointestinal stromal tumor in the retroperitoneum.
AB  - Gastrointestinal stromal tumor (GIST) is the most frequent non-epithelial
      neoplasm in the gastrointestinal tract. GIST has received much attention both for
      its clinical significance and biological nature, while the retroperitoneal
      condition identical to GIST has been rarely described. Presented herein is a case
      of GIST arising from the retroperitoneum in a 67-year-old man. The solid tumor
      measuring 4 cm was uncovered in the retroperitoneum, between the abdominal aorta
      and inferior vena cava, on computed tomography. The patient underwent surgical
      excision of the tumor. Histological examination showed proliferating spindle
      cells in the clearly demarcated tumor; immunoreactivity for Kit and CD34 in tumor
      cells confirmed the diagnosis of GIST. The histological origin of GIST is
      suggested to be gastrointestinal pacemaker cells, because they share specific
      immunoreactivity for CD117/Kit, which is also relevant to pathogenesis of GIST.
      The present case was a rare primary GIST in the retroperitoneum with typical
      immunopathological features.

PMID- 16984564
TI  - Surgical mesh used for an inguinal herniorrhaphy acting as a nidus for a bladder
      calculus.
AB  - We describe an unusual case of surgical mesh used in laparoscopic inguinal
      herniorrhaphy acting as a nidus for a bladder calculus.

PMID- 16984565
TI  - Protocol consisting of cisplatin, etoposide and irinotecan induced complete
      pathological remission of primary small cell carcinoma of the bladder.
AB  - A 73-year-old man with primary small-cell carcinoma of the bladder was treated by
      radical cystectomy with neoadjuvant chemotherapy. Pathological complete remission
      was achieved by combination chemotherapy composed of cisplatin, etoposide and
      irinotecan. The patient is free of disease 19 months after surgery.

PMID- 16984566
TI  - Experience of the treatment with gemcitabine, docetaxel, and carboplatin (GDC)
      chemotherapy for patients with small-cell carcinoma of the prostate.
AB  - Small-cell carcinoma of the prostate (SCCP) is a rare entity. Many treatment
      modalities have been done, but thus far no uniform treatment has been clearly
      established. We carried out combination chemotherapy with gemcitabine, docetaxel,
      and carboplatin (GDC) regimen (for two patients with refractory SCCP. Case 1
      involved a 53-year-old man diagnosed with SCCP after receiving hormone therapy
      for prostate cancer (stage D1). Six cycles of GDC chemotherapy was applied.
      Initially the primary site reduced according with a decline of neuro-specific
      enolase and with relief of the symptoms; however, bone disease occurred and he
      died of cancer 13 months after diagnosis of SCCP. Case 2 involved a 69-year-old
      man complaining of severe anal pain. He underwent a biopsy and a huge prostate
      tumor showing SCCP was showed. He had pelvic node metastases but no distant
      lesions, and received four cycles of GDC chemotherapy. He was discharged after
      receiving subsequent radiotherapy and remained stable for a while; however, he
      died of possible drug-induced hepatitis. This is the first report of chemotherapy
      with GDC against patients with SCCP. This regimen raised the possibility that it
      would intensify the outcome, which had been poorly achieved.

PMID- 16984567
TI  - Complete response, as determined by prostate-specific antigen level, to
      chlormadinone acetate withdrawal persisting longer than 2 years in patients with
      advanced prostate cancer: two case reports.
AB  - Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in
      prostate cancer. However, responses to AWS are usually of limited duration, and a
      complete response (CR) is extremely rare. We present two patients who exhibited a
      chemical CR for more than 2 years after the discontinuation of steroidal
      antiandrogen chlormadinone acetate use. Whether patients who respond to
      antiandrogen withdrawal include a group of patients with a better prognosis
      remains uncertain. However, considering that the usual survival period of
      patients with hormone-resistant prostate cancer is approximately 12 months, both
      of the patients reported here, who are present in excellent physical condition,
      exhibiting an improved quality of life, and attending their hospital as
      outpatients, obviously acquired a prolonged survival because of AWS.

PMID- 16984568
TI  - Testicular seminoma associated with massive necrosis.
AB  - A 70-year-old man presented with 2 years history of a painless hard mass in the
      left scrotum. Both pelvic computed tomography and magnetic resonance image showed
      enhancement only in the wall of the tumor, indicating a benign disease, rather
      than a neoplastic lesion. Physical examination 3 weeks after the first
      presentation showed the remarkable reduction of the left testicular size. Left
      inguinal orchiectomy was carried out and pathological diagnosis was seminoma with
      extensive necrotic areas occupying mostly the tumor. Either shrinkage or
      enlargement of testicular size with a long history demands full investigation for
      malignancy.

PMID- 16984571
TI  - Trends in wound care--the development of a specialty.

PMID- 16984572
TI  - Trends in wound care--our changing environment.

PMID- 16984573
TI  - Surgical treatment of hidradenitis suppurativa: case series and review of the
      literature.
AB  - The chronic and relapsing nature of hidradenitis suppurativa leads to physical
      and psychological damage. The absence of a proven cure further worsens the
      scenario. Patient 1 was a 28-year-old woman with a 10-year history of abscesses
      and non healing sinuses with foul-smelling discharge from her axilla, submammary
      and groin areas. This led to an episode of self-harm due to severe depression.
      After failed medical therapy, she was referred for surgery with wide excision of
      the skin and healing by secondary intention. Her wounds were managed by our
      specialist wound clinic with the use of topical and systemic antibiotics and thus
      remained free from symptoms. Patient 2 was a 32-year-old woman with a similar
      history for 15 years. Patient 3 was a 41-year-old man with a 20-year history of
      discharging sinuses and abscesses. All the patients had endured a long period of
      medical treatment and subsequently required surgery for a long-term relief of
      symptoms. This has undoubtedly led to psychological symptoms and a decrease in
      quality of life.

PMID- 16984574
TI  - Topical application of the tumour necrosis factor-alpha antibody infliximab
      improves healing of chronic wounds.
AB  - The role of tumour necrosis factor-alpha (TNF-alpha) in wound healing is not
      clear. Elevated levels of TNF-alpha have been observed in fluids from chronic
      wounds and have been shown to decrease over time during the healing process.
      Therapeutic antibodies such as infliximab can inhibit TNF-alpha activity. In this
      case series, we applied infliximab topically to eight patients with chronic
      ulcers of more than 4-month durations. The ulcers had multifactorial aetiology,
      with chronic venous insufficiency being the most prominent factor. All the ulcers
      had failed to respond to any previous conventional treatment. Infliximab was
      applied repeatedly to ulcers either as a 10 mg/ml solution and covered with an
      adhesive sheet or as a gel formulation (0.45, 1, or 4.5 mg/g) under a hydrofiber
      dressing/adhesive sheet. Improvement was assessed by measuring the percentage of
      change in the ulcer surface area. Seven of the eight patients (12 of 14 ulcers)
      responded to treatment with infliximab. After 4 weeks of treatment, surface area
      was reduced by more than 50% in 6 of the 14 treated ulcers. Within 8 weeks, five
      ulcers completely healed, while another four were reduced by more than 75% in
      size. Chronic, therapy-resistant leg ulcers responded well to repeated topical
      administration of a solution or a gel containing the TNF-alpha antibody,
      infliximab. Randomised controlled studies should be conducted to further evaluate
      the effect of topical infliximab on chronic wound healing.

PMID- 16984575
TI  - The use of an acellular dermal regenerative tissue matrix in the treatment of
      lower extremity wounds: a prospective 16-week pilot study.
AB  - A prospective, single-centre, randomized controlled study was performed to
      evaluate the effectiveness of Graftjacket, a human acellular regenerative tissue
      matrix as a treatment option for chronic non healing lower extremity wounds.
      Twenty-eight diabetic patients with full-thickness wounds that had been present
      for at least 6 weeks were treated with sharp debridement and randomized to a
      single application of Graftjacket tissue matrix plus mineral oil-soaked fluff
      compression dressing or to a control treatment of wound gel with gauze dressings.
      All patients were seen weekly. By week 16, 12 of 14 patients treated with
      Graftjacket tissue matrix demonstrated complete wound closure compared with 4 of
      14 patients in the control group. Patients treated with Graftjacket tissue matrix
      showed a statistically significant higher percentage of wound healing with
      respect to wound area, and clinically significant differences in wound depth and
      wound volume. This comparison is not performed to demonstrate that the
      application of the Grafjacket is more effective than sharp debridement. This
      study is done to help assign a role to the use of Graftjacket matrix in lower
      extremity wound care.

PMID- 16984576
TI  - Diabetic foot screening: why is it neglected?
AB  - Understanding reasons for the neglect of foot screening during the annual review
      of people with diabetes enables the development of solutions for this omission.
      This study explores the reasons within the context of health care delivery
      systems in terms of the professional, social, political and economic aspects of
      this screening. Information was obtained through reviewing publications on
      diabetic foot and health care reform. The omission of annual foot examination for
      people with diabetes is attributed to the nature of diabetes-related foot
      problems, people with diabetes, health care professionals and the current
      structure of health care delivery systems. Increasing the adherence to foot
      screening for those with diabetes requires short- and long-term strategies. Short
      and long-term strategies for reminding patients and staff about foot screening
      are suggested.

PMID- 16984577
TI  - Altered skin blood perfusion in areas with non blanchable erythema: an
      explorative study.
AB  - Non blanchable erythema, i.e. stage I pressure ulcer, is common in patients in
      acute and geriatric care and in nursing homes. Research has shown that this type
      of lesions is prone to develop into more severe pressure ulcers. The peripheral
      skin blood perfusion is of major importance for the development of pressure
      ulcers. The aim of this study was to explore the peripheral skin blood perfusion
      over time, in areas with non blanchable erythema and in corresponding undamaged
      areas on the opposite side of the body. A total of 19 measurements were
      performed, over time, using a laser Doppler perfusion imager. The blood flow
      distribution profiles over areas with non blanchable erythema and undamaged skin
      were found to be different. As the area of the non blanchable erythema decreased,
      the blood perfusion distribution profiles gradually became more heterogeneous; an
      area of high blood perfusion in the centre of the lesions was seen and the
      perfusion successively decreased closer to the edge. These results indicate that
      there are differences in blood perfusion between skin areas of non blanchable
      erythema and undamaged skin. The results also indicate that the visible redness
      in areas with non blanchable erythema is related to altered blood perfusion. The
      skin blood perfusion also seems to increase in relation to the size of the non
      blanchable erythema.

PMID- 16984578
TI  - Multiple bacterial species reside in chronic wounds: a longitudinal study.
AB  - The aim of the study was to investigate the bacterial profile of chronic venous
      leg ulcers and the importance of the profile to ulcer development. Patients with
      persisting venous leg ulcers were included and followed for 8 weeks. Every second
      week, ulcer samples were collected and the bacterial species present were
      identified. More than one bacterial species were detected in all the ulcers. The
      most common bacteria found were Staphylococcus aureus (found in 93.5% of the
      ulcers), Enterococcus faecalis (71.7%), Pseudomonas aeruginosa (52.2%), coagulase
      negative staphylococci (45.7%), Proteus species (41.3%) and anaerobic bacteria
      (39.1%). Resident bacterial species were present in all the ulcers. In 76% of the
      ulcers, two or more (up to five) resident bacterial species were found. The most
      common resident bacterial species were S. aureus and P. aeruginosa. Furthermore,
      ulcers with P. aeruginosa were found to be significantly larger than ulcers
      without the presence of P. aeruginosa (P < 0.005). Our study demonstrated that
      the chronic wound is colonised by multiple bacterial species and that once they
      are established many of them persist in the wound. Our results suggest that the
      presence of P. aeruginosa in venous leg ulcers can induce ulcer enlargement
      and/or cause delayed healing.

PMID- 16984579
TI  - Epidermal growth factor intralesional infiltrations can prevent amputation in
      patients with advanced diabetic foot wounds.
AB  - This study examined if a series of epidermal growth factor (EGF) local
      infiltrations can enhance the healing process of complicated diabetic wounds.
      Twenty-nine in-hospital patients with diabetic neuropathic or ischaemic lesions
      with high risk of amputation were treated in a non controlled pilot study
      conducted at the National Institute of Angiology, Havana. Lesions, classified as
      Wagner's grade 3 or 4, included ulcers > or = 20 cm2 for > or = 25 days or
      amputation residual bases > or = 30 cm2 for > or = 15 days, healing refractory
      despite comprehensive wound care. EGF (25 microg) intralesional infiltrations
      (approximately 250 microl of a 25 microg/ml solution/injection point) were
      performed thrice weekly up to the eighth week. Wound closure was monitored during
      the treatment and recurrence examined for a year following discharge from
      hospital. Eighty-six per cent of the patients treated showed a productive
      granulation at infiltration session 8. Histological examination at this point
      indicated a substantial wound matrix transformation, granulation tissue cell
      repopulation and angiogenesis. Of the 29 patients treated, amputation was
      prevented in 17 (58.6%) of them who completed 24 infiltration sessions. They
      averaged 71.1 +/- 18.3% of reepithelisation during a mean in-hospital period of
      66.5 +/- 4.9 days. Wound recurrence after 1 year of follow-up appeared in only
      one patient. Preliminary evidences suggest that EGF intralesional infiltrations
      may be effective in reducing diabetic lower limb amputation.

PMID- 16984580
TI  - Validation of a diabetic foot surgery classification.
AB  - The purpose of this project was to evaluate associations of increasing diabetic
      foot surgery stage with postoperative outcome. This project, designed as a
      retrospective cohort model, was conducted at three large, urban referral-based
      diabetic foot clinics. The investigators abstracted medical records from 180
      patients with diabetes, 76.1% male, aged 57.8 +/- 11.2 years, falling equally
      into four classes of a previously reported diabetic foot surgery classification
      system. These classes included class 1 (elective), class 2 (prophylactic), class
      3 (curative) and class 4 (emergency). There was a significant trend towards
      increasing risk of ulceration/reulceration (chi2(trend) = 17.8, P = 0.0001), peri
      postoperative infection (chi2(trend) = 96.9, P = 0.0001), all-level amputation
      (chi2(trend) = 41.7, P = 0.001) and major amputation (chi2(trend) = 8.6, P =
      0.003), with increasing class of foot surgery. The results of this study suggest
      that a non vascular foot surgery classification system including variables such
      as the presence or absence of neuropathy, an open wound and acute infection may
      be predictive of peri- and postoperative complications. This may assist the
      surgeon in better identifying risk when determining a rationale for and type of
      surgery in persons with diabetes.

PMID- 16984581
TI  - Healing of large midline wounds in infants: unlike in adults, does conservative
      approach give better results? Two case reports and review of the literature.
AB  - The case of two infants with large midline wounds, one with an omphalocele and
      the other with a lumbosacral wound secondary to ruptured meningocele, is reported
      wherein the advantages of leaving such wounds in infants to heal spontaneously
      over surgical intervention are shown. In this report, the cases are discussed and
      the literature is reviewed. It is concluded that the midline wounds in infants
      yield better results if left to heal spontaneously.

PMID- 16984582
TI  - Portal systemic collateral development: is it a trophic adaptation mechanism to
      hepatic deprivation?

PMID- 16984583
TI  - Endoscopic ultrasound-guided fine needle aspiration biopsy: equipment and
      technique.
AB  - Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) is currently
      performed on a routine basis at many endoscopic centers and it is evident that
      this procedure has a major impact on the therapeutic management of patients by
      obtaining a definite tissue diagnosis from lesions outlined by endosonography.
      The reported yield of EUS-FNA is about 90-95%, with an overall sensitivity and
      specificity of 90% and 100%, respectively. Moreover, even minute lesions down to
      a size of 5 mm may be imaged and consequently biopsied. This Review describes the
      technique of EUS-FNA in detail, based on a literature review and the authors'
      extensive experience with this method. The endoscopes and needle systems
      available on the market are presented in detail. The biopsy procedure is
      carefully explained, as well as the preparation of the cytology smears. Finally,
      the limitations and complications of the procedure are reviewed in brief,
      stressing the low rate of complications (below 1-2%), most of them being minor
      and self-limiting. Currently endosonography has strengthened its position as a
      diagnostic and staging method, especially after establishing the method of FNA
      biopsy. Thus, EUS-FNA is very useful to establish an initial tissue diagnosis of
      malignancy, but also to accurately stage the patients preoperatively, influencing
      the decision-making process and reducing the morbidity and mortality that
      accompanies inappropriate surgical interventions in patients with advanced
      cancer.

PMID- 16984584
TI  - Difference in localization of esophageal mucosal breaks among grades of
      esophagitis.
AB  - BACKGROUND: Gastroesophageal reflux occurs mainly during the daytime in patients
      with Los Angeles grade A esophagitis, but predominantly during the night in
      patients with grade C and D esophagitis. The purpose of the present paper was to
      investigate whether this difference in the pattern of gastroesophageal reflux
      influences the circumferential localization of erosions in the esophageal wall.
      METHODS: The subjects were 394 consecutive patients diagnosed endoscopically as
      having reflux esophagitis (grade A, n = 223; B, n = 93; C, n = 53; D, n = 25
      cases). Their endoscopic films were reviewed retrospectively to determine the
      circumferential location of esophageal mucosal breaks, and also the prevalence
      and size of hiatal hernia (HH). RESULTS: The numbers of mucosal breaks analyzed
      in patients with grade A, B and C esophagitis were 321, 173 and 54, respectively.
      Patients with grade A and B esophagitis had longitudinal mucosal breaks mainly in
      the right-anterior wall of the lower esophagus, whereas patients with grade C
      esophagitis had transverse mucosal breaks mainly in the posterior wall. The
      prevalence and size of HH was significantly higher and larger, respectively, in
      patients with grade C or D esophagitis than in those with grade A and B
      esophagitis. CONCLUSION: The circumferential location of esophageal mucosal
      breaks differs significantly among different grades of esophagitis.

PMID- 16984585
TI  - Modified technique of high-resolution ultrasonography of the normal cervical
      esophagus.
AB  - BACKGROUND AND AIM: To study a modified technique of neck ultrasound for the
      visualization of cervical esophagus using a high-resolution and high frequency
      linear transducer in normal subjects. METHODS: Consecutive control subjects were
      patients who underwent abdominal sonography for other diseases and had no past or
      current history of dysphagia or esophageal disorders. The thyroid gland was used
      as a transducer window to obtain images. We used a slightly flexed neck position
      with the head turned 45 degrees to the opposite side while scanning the neck on
      either side. RESULTS: One-hundred subjects were scanned and their age range was
      10-74 years (male:female ratio 1:1). In 36% of cases it was difficult to
      visualize the right lateral 2/3rd in the traditional scanning position of the
      neck. This improved to 2% with the modified neck position. All patients had the
      left window visualized with both neck positions. The transverse diameter,
      anterior-posterior diameter and wall thickness measures were all significantly
      greater with the modified technique. All patients tolerated the procedure with no
      reported discomfort. CONCLUSIONS: This modified technique provides superior views
      of the cervical esophagus, particularly from the right window, in almost all
      patients. Normal parameters using ultrasound have now been established.

PMID- 16984586
TI  - Influence of acid suppressants on gastric emptying: cross-over analysis in
      healthy volunteers.
AB  - BACKGROUND: Gastric emptying plays an important role in gastroesophageal reflux
      disease. Acid suppressants such as H2 receptor antagonists and/or proton pump
      inhibitors are often used in patients with gastroesophageal reflux disease.
      However, it remains controversial whether H2 receptor antagonists and proton pump
      inhibitors delay or accelerate gastric emptying. Here, the influence of acid
      suppressants on gastric emptying was evaluated via a cross-over study using the
      [13C]-labeled acetate breath test. METHODS: Twenty normal male subjects without
      gastroesophageal reflux disease symptoms were enrolled. Gastric emptying was
      investigated five times in every subject by the [13C]-labeled acetate breath test
      with oral administration of the vehicle, domperidone, and three acid
      suppressants: ranitidine, famotidine and rabeprazole. Gastric emptying was
      estimated by the values of T(max-calc), T(1/2) and %dose/2 h calculated from the
      13CO2 breath excretion curve. RESULTS: Using the T(max-calc) values, rabeprazole,
      ranitidine and famotidine did not influence gastric emptying time in comparison
      with vehicle administration. Using the T(1/2) and %dose/2 h values, rabeprazole
      tended to delay gastric emptying. Domperidone produced a statistically
      significant acceleration of gastric emptying for all three variables (P < 0.05).
      CONCLUSION: Oral dosage of the H2 receptor antagonists, ranitidine and
      famotidine, has no significant effect on gastric emptying. However, rabeprazole
      may delay gastric emptying more strongly than H2 receptor antagonists.

PMID- 16984587
TI  - Zinc L-carnosine protects against mucosal injury in portal hypertensive
      gastropathy through induction of heat shock protein 72.
AB  - BACKGROUND AND AIMS: Increased susceptibility to gastric mucosal injury is
      observed in portal hypertensive gastropathy (PHG). In this study, the effects of
      zinc L-carnosine, an anti-ulcer drug, were evaluated on expression of heat shock
      protein (hsp) 72 and cytoprotection in gastric mucosa in a rat model of PHG.
      METHODS: Portal hypertensive gastropathy with liver cirrhosis was induced by bile
      duct ligation for 4 weeks in male Sprague-Dawley rats. Expression of gastric
      mucosal hsp72 was evaluated by Western blotting at 6 h after intragastric
      administration of L-carnosine, zinc sulfate, or zinc L-carnosine. Blood was also
      collected for determination of serum zinc level. Mucosal protective abilities
      against hydrochloric acid (HCl) (0.6N) followed by pretreatment with L-carnosine,
      zinc sulfate or zinc L-carnosine were also studied. RESULTS: L-carnosine, zinc
      sulfate, and zinc L-carnosine induced hsp72 in gastric mucosa of rats with bile
      duct ligation. Zinc sulfate and zinc L-carnosine suppressed HCl-induced mucosal
      injury. However, L-carnosine could not suppress HCl-induced mucosal injury. Serum
      zinc levels were significantly elevated after zinc L-carnosine administration.
      Furthermore, pretreatment with zinc L-carnosine (30-300 mg/kg) increased the
      expression of hsp72 in gastric mucosa and prevented HCl-induced mucosal injury in
      rats with bile duct ligation in a dose-dependent manner. CONCLUSIONS: Zinc
      derivatives, especially zinc L-carnosine, protected portal hypertensive gastric
      mucosa with increased hsp72 expression in cirrhotic rats. It is postulated that
      zinc L-carnosine may be beneficial to the mucosal protection in PHG as a
      'chaperone inducer'.

PMID- 16984588
TI  - Safer endoscopic gastric mucosal resection: preoperative proton pump inhibitor
      administration.
AB  - BACKGROUND AND AIM: Control of bleeding is crucial in improving the safety of
      endoscopic mucosal resection (EMR), and intragastric acidity has a great impact
      on hemostasis and blood coagulation. Proton pump inhibitors (PPI) are potent
      suppressors of gastric acid; however, PPI need to be continuously administered
      orally for several days, and thus initial effects may be insufficient if PPI is
      only administered immediately after EMR. The aim of this study was to determine
      whether preoperative administration of PPI prior to EMR can elevate intragastric
      acidity, facilitate better control of intraoperative bleeding (complete
      coagulation and hemostasis), prevent postoperative bleeding, and facilitate
      healing of artificial ulcers. METHODS: A randomized clinical study was conducted
      in which EMR was performed with or without 1 week of preoperative PPI
      administration. RESULTS: Artificial ulcers created by EMR healed more rapidly in
      patients who received preoperative PPI. CONCLUSIONS: The results of the study
      suggest that preoperative administration of PPI before EMR is useful for
      controlling and preventing bleeding, and for facilitating the healing of
      artificial ulcers.

PMID- 16984589
TI  - Highly salted food and mountain herbs elevate the risk for stomach cancer death
      in a rural area of Japan.
AB  - BACKGROUND: Although many case-control and experimental studies have shown that
      highly salted foods are risk factors for stomach cancer, only a few cohort
      studies have supported the relationship. METHODS: In a cohort study conducted in
      a rural area of Japan, 8035 residents aged over 30 years (approx. 55% were
      female) filled out a questionnaire. Seventy-six of them died from stomach cancer
      during an 11-year follow-up period. In the questionnaire, intake frequencies of
      29 food items, smoking and drinking habits were investigated. Tsukemono (pickled
      vegetables) and tsukudani (foods deep boiled in soy sauce) are highly salted
      foods in the area. Frequency of each food item intake was classified into three
      levels, and age- and sex-adjusted risks were calculated using proportional hazard
      models. RESULTS: In the final model obtained by backward elimination, frequent
      intake of tsukemono and tsukudani and that of mountain herbs remained as
      significant risk factors. Compared with the least frequent intake, risk (95%
      confidence interval) of the most frequent intake was 5.4 (1.8-16.3) for highly
      salted foods (P for trend < 0.01) and 3.7 (1.4-9.6) for mountain herbs (P for
      trend = 0.04). CONCLUSION: Highly salted foods and mountain herbs were important
      risk factors for death from stomach cancer.

PMID- 16984590
TI  - Prevalence of irritable bowel syndrome in Korea: population-based survey using
      the Rome II criteria.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common functional
      gastrointestinal disorder in the West. But information on the prevalence of IBS
      in Asia is still lacking, especially in Korea. Therefore, the aims of the present
      study were to estimate the prevalence of IBS in the general population of Korea
      and also to investigate characteristics of IBS and health-care-seeking behavior
      of IBS patients. METHODS: Telephone interview survey was conducted by Gallup,
      Korea using a validated questionnaire based on the Rome II criteria. The response
      rate of the telephone interview survey was 25.2% (n = 1066, 535 male and 531
      female responders). A random sample of gender and age (between 18 and 60 years),
      based on a per capita ratio was obtained. RESULTS: Among 1066 subjects, the
      prevalence of IBS was 6.6% (70 subjects; 7.1%, male; 6.0%, female). The
      difference in IBS prevalence by gender was not significant. The prevalence was
      higher among those in their 20s (P = 0.036). Among 70 subjects with IBS, 10/20
      IBS subjects sought health care due to abdominal pain. Among the risk factors of
      IBS, marital status had a significant difference; the following risk factors are
      arranged in descending order: age (odds ratio [OR]: 1.38, 95% confidence interval
      [CI]: 0.85-2.25), alcohol intake (OR: 1.38, 95%CI: 0.81-2.35), gender (OR: 1.19,
      95%CI: 0.73-1.94), demographics (OR: 1.09, 95%CI: 0.53-2.25), income (OR: 0.88,
      95%CI: 0.54-1.45), education level (OR: 0.81, 95%CI: 0.46-1.40), smoking (OR:
      0.64, 95%CI: 0.37-1.12), and marital status (OR: 0.59, 95%CI: 0.35-0.99).
      CONCLUSIONS: The prevalence of IBS in the Korean population is 6.6%, and the
      male:female ratio is similar. Also, IBS is more frequent in younger subjects.
      Irritable bowel syndrome subjects visited a physician mostly due to abdominal
      pain.

PMID- 16984592
TI  - The Vienna classification applied to colorectal adenomas.
AB  - BACKGROUND AND AIM: In 1999, a group of Western and Asian pathologists gathered
      in Vienna reached consensus regarding the classification of gastrointestinal
      epithelial neoplasia. In this study, that classification is applied to colorectal
      adenomas. METHODS: Colorectal adenomas from 1552 patients were histologically
      classified according to the categories listed in Vienna: category 3, low-grade
      dysplasia; 4.1, high-grade dysplasia; 4.2, carcinoma in situ; 4.3, suspicious of
      intramucosal carcinoma; 5.1, intramucosal carcinoma; and 5.2, submucosal
      carcinoma. The criteria used to diagnose these lesions are described in detail.
      Adenomas with dysplasia (categories 3 and 4.1) or with carcinoma (categories 4.2,
      4.3, 5.1 and 5.2) were analyzed separately. On basis of their configuration,
      adenomas were classified into tubular, tubulovillous, villous, serrated,
      microtubular and combined phenotypes (i.e. other than tubulovillous). RESULTS:
      The highest percentage of adenomas with carcinoma was found amongst villous
      adenomas (29.6%), followed by combined adenomas (27.8%). Villous adenoma with
      carcinoma was the most frequent neoplasia at all ages; combined adenomas with
      carcinoma were more frequent among younger patients. In elderly patients (> or =
      60 years of age) the highest percentage of adenomas with carcinoma was recorded
      in villous adenomas (28.1%), followed by serrated adenomas (19.2%). Villous
      adenomas and combined adenomas with carcinoma were more frequent in males.
      CONCLUSION: The Vienna classification of colorectal adenomas seems to be
      influenced by parameters inherent to the patient such as age and sex and by the
      histological phenotype of the adenoma. With the recent improvement in medical
      technology it is possible to laser-microdissect a defined group of neoplastic
      glands (such as with carcinoma in situ or with intramucosal carcinoma) for
      specific molecular analysis. This modern technology will permit in future the
      translation of histological structures into molecular terms.

PMID- 16984591
TI  - Incidence and odds ratio of appendicitis as first manifestation of colon cancer:
      a retrospective analysis of 1873 patients.
AB  - BACKGROUND AND AIM: Obstruction of the lumen of the appendix is the major cause
      of appendicitis. Tumors could obstruct this lumen and cause appendicitis in the
      elderly. The association between appendicitis and colon cancer has not been
      sufficiently investigated, and this study was designed to clarify this
      association. METHODS: This was a retrospective study. Patients diagnosed with
      acute appendicitis from January 1998 to December 2003 at the Taipei Veterans
      General Hospital were surveyed. Patients found to have colon cancers immediately
      or subsequently after appendectomy were included and analyzed. RESULTS: A total
      of 1873 patients were diagnosed as having appendicitis of whom 16 were found to
      have colon cancer. The incidence of appendicitis associated with colon cancer was
      0.85%. The time from appendectomy to the recognition of colonic cancer was at a
      median delay of 5.8 months. From the Taiwan Cancer Research Annual Report, the
      incidence of colon cancer was 31.91/100,000 in the year 2000. The odds ratio of
      colon cancer incidence had a 38.5-fold increase among patients older than 40 with
      acute appendicitis. CONCLUSIONS: In patients over 40 years who present with
      symptoms of acute appendicitis the possibility of a coexistent colonic neoplasm
      should always be kept in mind. These patients should undergo colonoscopy 6 weeks
      after surgery to exclude the possibility of a coexistent colorectal cancer.

PMID- 16984593
TI  - Endoscopic therapy for bleeding esophageal varices improves the outcome of Child
      C cirrhotic patients.
AB  - BACKGROUND AND AIM: Bleeding from esophageal varices is one of the frequent
      severe complications arising in patients with liver cirrhosis. The management of
      esophageal varices is therefore important for patient survival. The purpose of
      this study was to clarify the predictive factors for mortality in patients with
      Child C cirrhosis presenting with variceal bleeding. METHODS: A retrospective
      analysis of 77 Child C cirrhotic patients with bleeding from esophageal varices
      was conducted. All patients received endoscopic therapy. Twenty-nine patients
      received endoscopic variceal ligation, and 48 patients received endoscopic
      injection sclerotherapy or endoscopic injection sclerotherapy with ligation.
      Univariate and multivariate analyses of clinical data were performed to identify
      the prognostic factors for survival for these 77 patients. RESULTS: Fifty-seven
      of 77 patients received endoscopic therapy within 24 h after variceal bleeding,
      and bleeding was controlled in 55 (96.5%). The remaining 20 patients received
      endoscopic therapy more than 24 h after bleeding. Higher bilirubin level and
      rebleeding were the predictive parameters for 6-week survival in the 77 patients,
      according to univariate and multivariate analysis. Higher bilirubin level,
      refractory ascites, and the presence of hepatocellular carcinoma were the
      predictive parameters for mortality in 77 patients as determined by multivariate
      analysis. CONCLUSIONS: Endoscopic therapy was effective in controlling acute
      variceal bleeding of Child C cirrhotic patients. The prognosis of Child C stage
      patients presenting with variceal bleeding depended on the severity of liver
      damage and the presence of hepatocellular carcinoma.

PMID- 16984594
TI  - Estimation of standard liver volume in Japanese living liver donors.
AB  - BACKGROUND: Standard liver volume (SLV) is an important concept in adult living
      liver donor transplantation. The purpose of this study was to re-evaluate and
      modify the authors' previous formula for predicting total liver volume (TLV).
      METHODS: The TLV of 301 Japanese living donors was measured by computed
      tomography. This TLV was then compared with the liver volume calculated using
      established formulas. The correlation between TLV and several factors including
      body surface area (BSA) were analyzed and a new equation (SLVn) to better
      approximate TLV was determined. Factors related to the difference between TLV and
      SLVn were examined. RESULTS: Average TLV was 1196.3 +/- 221.0 cm3. Urata's
      formula underestimated TLV by 17.6 cm3 and the other formulas overestimated it by
      120.4-244.9 cm3. TLV could be approximated by BSA; SLVn (cm3) = -404.8 + 961.3 x
      BSA (m2, R2 = 0.58). SLVn tended to overestimate the TLV of older donors and to
      underestimate TLV of thin donors. CONCLUSIONS: A new simple formula is presented
      that might be a better fit for calculating TLV in Japanese adults. This formula
      might be useful for evaluating the size of an adequate graft.

PMID- 16984595
TI  - Kinetics of indocyanine green removal from blood can be used to predict the size
      of the area removed by radiofrequency ablation of hepatic nodules.
AB  - BACKGROUND AND AIM: The size of radiofrequency ablation (RFA) in the liver can be
      negatively influenced by the surrounding blood flow. The indocyanine green (ICG)
      test can be used to evaluate the effective blood flow in the liver, and distance
      from the hilus can affect local blood flow. The aim of this study was to assess
      whether the ICG test or distance from the hilus could be used to predict the size
      of the ablated area in liver by RFA treatment of hepatocellular carcinoma (HCC)
      nodules. METHODS: The RFA measurements of 44 HCC nodules in 39 patients were
      retrospectively studied. Cases were included if they met the following criteria:
      (i) no catheter treatment before RFA; (ii) no movement of the RFA device; (iii)
      strict ablation time; and (iv) only one ablation. In all patients, ICG-R15
      testing was done immediately before RFA and the initial therapeutic efficacy was
      evaluated by dynamic computed tomography scanning 2-5 days after RFA. The
      correlation between the maximum size of the RFA area and the ICG test results or
      the distance of the target area from the hilus (site of first portal vein
      divergence) were analyzed statistically. RESULTS: The ICG-R15 result was
      significantly correlated with the maximum diameter of the ablated area both in 2
      cm-electrode tip length (R2 = 0.35, P = 0.0012), and in 3 cm-tip length (R2 =
      0.26, P = 0.0377). Multiple-regression analysis showed that the electrode tip
      length (P = 0.0010) and ICG-R15 (P = 0.0046) were independent factors that could
      predict the maximum diameter of the RFA area. CONCLUSION: The results of ICG
      testing can be used to predict the size of the area that will be ablated at a
      target liver site before RFA treatment.

PMID- 16984596
TI  - Growth inhibitory effects of interferon-alpha subtypes vary according to human
      liver cancer cell lines.
AB  - BACKGROUND: Interferon (IFN)-alpha preparations used in the treatment of viral
      and neoplastic disease consist of single or multiple IFN-alpha subtypes that may
      possess different biological activity, but there are no data on liver cancer
      cells. METHODS: Antiproliferative effects and the mechanisms of growth inhibition
      of five IFN-alpha subtypes (alpha1, alpha2, alpha5, alpha8 and alpha10) were
      examined in vitro using 13 human liver cancer cell lines. RESULTS: The
      antiproliferative effect of each IFN-alpha subtype was different in each cell
      line. The 50% growth inhibitory concentration (IC50) on an antiviral unit basis
      showed that alpha5 presented the most potent antiproliferative effects in 11 of
      the 13 cell lines, and alpha8 in two cell lines. On average, the
      antiproliferative effects were strong in descending order from alpha5, alpha8,
      alpha10, alpha2 to alpha1. On weight basis, the most potent antiproliferative
      effect was shown by alpha8 in nine of the 13 cell lines, alpha5 in four cell
      lines, and the potency of the effects on average in descending order was alpha8,
      alpha5, alpha10, alpha2 and alpha1. No significant difference was observed
      between natural and recombinant alpha2. The mechanism of growth inhibition of
      each subtype in HAK-1B and KMCH-1 cell lines were apoptosis and S-phase arrest,
      and their induction levels were related to a certain degree to the
      antiproliferative effects. CONCLUSIONS: Our findings show that the
      antiproliferative effect of each IFN-alpha subtype varies according to the cell
      line, but that the cells are relatively or absolutely responsive to alpha5 and
      alpha8 subtypes.

PMID- 16984597
TI  - Involvement of retinoic acid-induced transglutaminase activity in zonal
      differences of hepatocyte proliferation after partial hepatectomy.
AB  - BACKGROUND: The authors have recently demonstrated that there is inverse
      correlation between transglutaminase (TGase) activity and DNA synthesis in
      periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) at 1 day after
      partial hepatectomy in rats. In order to ensure the involvement of TGase in the
      differential growth capacities between periportal and perivenous regions of
      regenerating liver, the aim of this study was to investigate the effect of
      retinoic acid, an inducer of TGase expression, on zonal differences of hepatocyte
      proliferation between PPH and PVH isolated from regenerating rat liver. METHODS:
      Regenerating liver was prepared by 70% partial hepatectomy. PPH and PVH
      subpopulations were isolated by the digitonin/collagenase perfusion technique.
      Cell cycle was evaluated for incorporation of BrdU into hepatocytes and detected
      by flow cytometric analysis. TGase activity was determined by incorporation of
      14C-putrescine into dimethylcasein. RESULTS: When retinoic acid was injected
      immediately after partial hepatectomy, TGase activity greatly increased in both
      PPH and PVH at 1 day after partial hepatectomy, and activity was higher in PPH
      than in PVH. DNA synthesis in both subpopulations did not increase 1 day after
      partial hepatectomy, with peaks of DNA synthesis shifting to 2 days, and
      synthesis was higher in PVH than in PPH. CONCLUSION: These results suggest that
      TGase might be involved in differential growth capacities between periportal and
      perivenous regions of regenerating rat liver after partial hepatectomy.

PMID- 16984598
TI  - Increased serum and hepatic tissue levels of interleukin-18 in patients with
      fulminant hepatic failure.
AB  - BACKGROUND: Fulminant hepatic failure is a serious clinical condition associated
      with a high mortality rate. Interleukin (IL)-18 is a pro-inflammatory cytokine
      that is associated with several inflammatory diseases. The purpose of the present
      paper was therefore to investigate whether IL-18 is elevated in patients with
      fulminant hepatic failure. METHODS: Serum levels of IL-18 were measured in
      patients with fulminant hepatic failure before and after liver transplantation.
      Native liver tissue samples were collected and the tissue levels of IL-18 were
      determined. Liver tissues were stained immunohistochemically with antihuman IL-18
      antibody. The serum levels of IL-1beta, IL-6, IL-8, IL-12, interferon-gamma, and
      tumor necrosis factor-alpha were also determined in patients with fulminant
      hepatic failure before and after liver transplantation. RESULTS: Elevated levels
      of IL-18 in serum and hepatic tissue were observed in patients with fulminant
      hepatic failure. Native liver tissue samples were immunohistochemically positive
      for IL-18. Interleukin-18 levels were markedly reduced after liver replacement.
      No other inflammatory cytokines were substantially elevated in patients with
      fulminant hepatic failure. CONCLUSION: The serum levels of IL-18 levels are
      elevated much more than those of other cytokines in patients with fulminant
      hepatic failure.

PMID- 16984599
TI  - Prevalence and risk factors of gallstone disease in an adult population of
      Taiwan: an epidemiological survey.
AB  - BACKGROUND AND AIMS: The aim of this study was to determine the prevalence and
      risk factors of gallstone disease (GSD) in an adult population of Taiwan through
      a population-based screening study. METHODS: A cross-sectional community study in
      a rural village of Taiwan was conducted in 3333 Chinese adults (aged > or = 18
      years) undergoing ultrasonography. A questionnaire on personal history was
      completed to ascertain whether the removed gallbladder contained stones in all
      cholecystectomized subjects, the dietary habits (vegetarian/non-vegetarian diet),
      the history of GSD in the participant's first-degree relatives, the history of
      gastrointestinal surgery (vagotomy, gastrectomy for peptic ulcer disease, or
      ileal resection), parity, and use of oral contraceptives. The demographic
      characteristics and biochemical parameters were recorded. RESULTS: The overall
      prevalence of GSD was 5.0% (4.6% in men, 5.4% in women) with no significant sex
      differences (men/women: odds ratio [OR] 0.71, 95% confidence interval [CI] 0.50
      1.01, P = 0.058). Logistic regression analysis showed that increasing age (men:
      40-64 years, OR 7.38, 95% CI 2.59-21.01, P < 0.001 and > or = 65 years, OR 14.16,
      95% CI 4.84-41.47, P < 0.001; women: 40-64 years, OR 4.08, 95% CI 1.90-8.75, P <
      0.001 and > or = 65 years, OR 6.78, 95% CI 2.97-15.46, P < 0.001) and the
      presence of fatty liver evidenced by ultrasonography (men: OR 2.24, 95% CI 1.32
      3.80, P = 0.003; women: OR 2.13, 95% CI 1.33-3.42, P = 0.002) were risk factors
      for GSD. Additionally, fasting plasma glucose > or = 126 mg/dL (OR 2.11, 95% CI
      1.16-3.83, P = 0.014), history of GSD in the first-degree relatives (OR 7.47, 95%
      CI 2.22-25.12, P = 0.001), and use of oral contraceptives (OR 10.71, 95% CI 3.06
      37.49, P < 0.001) were risk factors for GSD in women, but fasting plasma glucose
      > or = 126 mg/dL was only correlated to GSD without controlling for other
      confounding factors in men. Other demographic characteristics and biochemical
      parameters, such as high body mass index (> or = 25 kg/m2), increased parity,
      hypercholesterolemia, hypertriglyceridemia, hyperuricemia, hepatitis C infection
      and cirrhosis, did not exhibit any correlation to GSD in logistic regression
      analysis, although they appeared to be related to GSD in women in univariate
      analysis. CONCLUSIONS: Age and fatty liver in both sexes were found to be risk
      factors for GSD in the study population. The finding of a correlation between
      fatty liver and GSD is an important addition to the literature concerning the
      risk factors of GSD. Diabetes mellitus, history of GSD in the first-degree
      relatives, and use of oral contraceptives were also risk factors for GSD in
      women.

PMID- 16984600
TI  - Akt expression may predict favorable prognosis in cholangiocarcinoma.
AB  - BACKGROUND: Overexpression of signaling proteins including epidermal growth
      factor receptor (EGFR), Akt, mitogen activated protein kinase (MAPK) and
      cyclooxygenase-2 (COX-2) occurs in cholangiocarcinoma cell lines. However, the
      prognostic value of these markers is unknown. No prior study correlated the
      expression of these signaling proteins with clinical outcome. Further, co
      expression of these proteins has not been reported. Co-expression may reflect
      cross-talk between signaling pathways. The aim of this clinicopathological study
      was to investigate the overexpression and co-expression of EGFR and related
      signaling proteins in cholangiocarcinoma and explore their relationship to
      clinical outcome. METHODS: Twenty-four consecutive cases of cholangiocarcinoma
      treated from 1996 to 2002 at Roswell Park Cancer Institute were included.
      Immunohistochemical staining of paraffin-embedded tissue sections was performed
      using antibodies against Akt, p-Akt, MAPK, p-MAPK, COX-2, EGFR and p-EGFR. Two
      pathologists independently scored the protein expression. RESULTS: Cyclooxygenase
      2, Akt, and p-MAPK were commonly expressed in biliary cancers (100%, 96% and 87%
      of malignant cells, respectively). EGFR (60%) and p-EGFR (22%) overexpression was
      also detected. There was a significant association between EGFR and p-EGFR (P =
      0.027) and between Akt and p-Akt (P = 0.017) expression in tumor tissue. A
      noteworthy association was shown between MAPK and p-Akt (P = 0.054). Multivariate
      analysis using the Cox proportional hazard model identified the use of
      chemotherapy (hazard ratio [HR] = 0.039, P = 0.0002), radiation (HR = 0.176, P =
      0.0441) and Akt expression (HR = 0.139, P = 0.006) as the best predictors of
      overall prognosis. CONCLUSION: Epidermal growth factor receptor signaling
      intermediates are commonly expressed in cholangiocarcinoma. Expression of Akt and
      use of systemic chemotherapy or radiation may correlate with improved survival.

PMID- 16984601
TI  - Education and imaging. Hepatobiliary and pancreatic: Atrial kick and blood flow
      in hepatic veins.

PMID- 16984602
TI  - Education and imaging. Hepatobiliary and pancreatic: Choledochopancreatic fistula
      complicating acute pancreatitis.

PMID- 16984603
TI  - Education and imaging. Gastrointestinal: Hookworm diagnosed by capsule endoscopy.

PMID- 16984604
TI  - Education and imaging. Gastrointestinal: Leptospirosis and abdominal pain.

PMID- 16984605
TI  - Autoimmune hepatitis.

PMID- 16984606
TI  - Ganciclovir and the treatment of Epstein-Barr virus hepatitis.
AB  - Epstein-Barr virus (EBV) is part of the herpesvirus family that infects up to 90%
      of the population. Initial infection is often subclincal in children but will
      generally result in symptomatic infectious mononucleosis in adolescents and
      adults. Ganciclovir has been utilized in immunocompromised patients with EBV
      encephalitis and post-liver transplant for EBV fulminant hepatitis. Herein, the
      successful use of ganciclovir in two immunocompetent patients with severe EBV
      hepatitis is reported.

PMID- 16984607
TI  - Evaluation of postprandial 3 h pH monitoring for gastroesophageal reflux disease:
      is there a possibility of streamlining the 24 h test?

PMID- 16984608
TI  - Enteric duplication cyst of the pancreas presenting as acute abdomen in an adult.

PMID- 16984609
TI  - Proton pump inhibitors in acute non-variceal upper gastrointestinal bleeding.

PMID- 16984610
TI  - Sclerosing cholangitis associated with Wegener's granulomatosis.

PMID- 16984612
TI  - Quantitative assessment of RUNX3 methylation in neoplastic and non-neoplastic
      gastric epithelia using a DNA microarray.
AB  - Silencing of the RUNX3 gene by hypermethylation of its promoter CpG island plays
      a major role in gastric carcinogenesis. To quantitatively evaluate RUNX3
      methylation, a fiber-type DNA microarray was used on which methylated and
      unmethylated sequence probes were mounted. After bisulfite modification, a part
      of the RUNX3 promoter CpG island, at which methylation is critical for gene
      silencing, was amplified by polymerase chain reaction using a Cy5 end-labeled
      primer. Methylation rates (MR) were calculated as the ratio of the fluorescence
      intensity of a methylated sequence probe to the total fluorescence intensity of
      methylated and unmethylated probes. Five gastric cancer cell lines were analyzed,
      as well as 26 primary gastric cancers and their corresponding non-neoplastic
      gastric epithelia. MR in four of the cancer cell lines that lost RUNX3 mRNA
      ranged from 99.0% to 99.7% (mean, 99.4%), whereas MR in the remaining cell line
      that expressed RUNX3 mRNA was 0.6%. In primary gastric cancers and their
      corresponding non-neoplastic gastric epithelia, MR ranged from 0.2% to 76.5%
      (mean, 22.7%) and from 0.7% to 25.1% (mean, 5.5%). Ten (38.5%) of the 26 gastric
      cancers and none of their corresponding non-neoplastic gastric epithelia had MR
      >30%. Most of the samples with MR >10% tested methylation-positive by
      conventional methylation-specific polymerase chain reaction (MSP). This
      microarray-based methylation assay is a promising method for the quantitative
      assessment of gene methylation.

PMID- 16984613
TI  - Follicular lymphoma frequently originates in the salivary gland.
AB  - The aim of the present study was to examine the clinicopathological presentations
      of follicular lymphomas (FL) of the salivary glands, as compared to mucosa
      associated lymphoid tissue (MALT) lymphomas. A total of 27 primary salivary gland
      lymphomas were examined: 6 FL (five, grade 1; one, grade 2); 19 MALT lymphomas;
      and two diffuse large B-cell lymphomas. The FL patients ranged in age from 24 to
      73 years, with a mean of 49 years, which was younger than that of MALT patients
      (mean: 64 years; P < 0.05). Four of the six FL arose from the submandibular
      gland, which was the origin of only five out of a total of 19 MALT lymphomas. One
      FL patient was in clinical stage (CS) IE, two in CS IIE, and two in CS III and
      IV. As regards the MALT lymphoma patients, 13 (68%) were in CS IE and five (26%)
      in CS IIE. None of the FL patients had clinical diagnosis of autoimmune disease
      but eight MALT lymphoma patients had autoimmune disease. The present study found
      a relatively high incidence of FL in the salivary glands. The observed
      differences in age of onset, background of autoimmune disease, and lesion site
      suggests that the pathogenesis of FL may differ from that of MALT lymphoma.

PMID- 16984614
TI  - Absence of human herpesvirus-8 and Epstein-Barr virus in inflammatory
      myofibroblastic tumor with anaplastic large cell lymphoma kinase fusion gene.
AB  - Inflammatory myofibroblastic tumor (IMT) is clinically and histologically
      characterized by inflammation. Some populations of IMT have anaplastic large cell
      lymphoma kinase (ALK) gene rearrangements. Infection with Epstein-Barr virus
      (EBV) and human herpesvirus-8 (HHV-8) in tumor cells of IMT has been reported;
      these reports, however, have been limited to ALK-negative IMT. The purpose of the
      present paper was to evaluate 21 cases of IMT for the presence of EBV and HHV-8.
      Immunohistochemically, 15 cases were ALK positive and six were negative. Of eight
      cases analyzed using reverse transcription-polymerase chain reaction, tropomyosin
      3 (TPM3)-ALK, TPM4-ALK and clathrin heavy chain-ALK fusion genes were detected in
      one, two and two cases, respectively. All 21 IMT, irrespective of ALK expression,
      were negative for EBV by in situ hybridization for EBV-encoded RNA and
      immunohistochemical stain for latent membrane antigen-1. HHV-8 was also negative
      in all IMT by PCR for HHV-8 DNA sequence (KS330/233) and immunohistochemical
      stain for latent nuclear antigen. These results suggest that IMT may be a
      heterogeneous group in terms of pathogenesis, and EBV and HHV-8 do not play a
      major role in the pathogenesis of ALK-positive tumor.

PMID- 16984615
TI  - Usefulness of Ki-67 for predicting the metastatic potential of rectal carcinoids.
AB  - Rectal carcinoid <10 mm can be completely removed by endoscopic procedure.
      However, a few authors reported that small rectal carcinoids have the potential
      to metastasize. Therefore, histological parameters predicting their metastatic
      potential are necessary. The aim of the present study was to evaluate the
      usefulness of Ki-67 positive/negative area ratio (Ki-67 ratio) using computer
      assisted image analysis. A total of 43 patients with rectal carcinoids were
      retrospectively investigated. Twenty-eight patients underwent endoscopic
      resection and 15 patients underwent surgery. Nine of the 43 patients presented
      with metastatic disease. The Ki-67 ratio of all specimens was measured. Finally,
      the Ki-67 ratio was compared with other macroscopic or microscopic parameters for
      predicting lymph node or distant metastatic disease. The mean Ki-67 ratio of the
      metastatic and non-metastatic group was 3.9 and 1.0%, respectively (P < 0.01).
      The Ki-67 ratio was effective because of its high sensitivity (88.9%) and
      specificity (82.4%). Ki-67 ratio was superior to other microscopic parameters
      such as variation in nuclear size and vessel permeation. Ki-67 ratio was as
      effective as the other macroscopic parameters of tumor size and central
      depression. Based on these results it is suggested that Ki-67 is a reliable
      microscopic marker to predict metastatic potential of rectal carcinoids.

PMID- 16984616
TI  - Age-related alteration in the association of microsatellite instability with
      absent hMLH1 expression and histological types of colorectal carcinoma.
AB  - Microsatellite instability (MSI) is present in approximately 15-20% of sporadic
      colorectal cancers. However, despite the increased prevalence of absent hMLH1
      expression and MSI in colorectal cancer in the elderly, few attempts have been
      made to define it in detail. The aim of the present paper was to correlate age
      related alterations in absent hMLH1 expression and MSI with various histological
      types of colorectal carcinoma. hMLH1 expression and microsatellite status were
      studied in 184 colorectal carcinomas (49 well-differentiated, 49 moderately
      differentiated, 49 poorly differentiated adenocarcinomas, and 37 mucinous
      carcinomas). The prevalence of absent hMLH1 expression was higher in poorly
      differentiated adenocarcinoma (63%) and mucinous carcinoma (43%) than in well-
      (8%) and moderately (12%) differentiated adenocarcinomas. MSI was found more
      frequently in poorly differentiated adenocarcinoma (69%) and mucinous carcinoma
      (41%) than in well- and moderately differentiated adenocarcinomas (8% and 6%,
      respectively). Age-related differences in absent hMLH1 expression and MSI were
      found only in poorly differentiated adenocarcinoma, in which the prevalence of
      medullary-type carcinoma increased with advancing age. These results indicate
      that an age-related increase of medullary-type tumors in poorly differentiated
      adenocarcinoma may play an important role in the increase of absent hMLH1
      expression and MSI in colorectal carcinoma.

PMID- 16984617
TI  - Osteochondritis dissecans of the elbow: histopathological assessment of the
      articular cartilage and subchondral bone with emphasis on their damage and
      repair.
AB  - Osteochondritis dissecans (OCD) of the elbow is a localized injury of the
      articular cartilage and subchondral bone that is commonly seen in the young
      athlete. In the present study, the extent of damage and repair on the articular
      cartilage and subchondral bone was examined histologically using specimens of 25
      osteochondral cylinders and seven loose bodies obtained from 25 young athletes
      who had undergone osteochondral autograft surgery. Terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assays for detecting
      apoptotic cells and immunohistochemistry of matrix metalloproteinases (MMP) were
      performed on the osteochondral cylinder specimens. The histological findings of
      the OCD of the elbow showed that the articular cartilage exhibited degenerative
      change, mimicking osteoarthritis, and was markedly damaged as the lesion
      progressed. TUNEL-positive cells and MMP-3- and -13-expressing cells were
      distributed in the degenerative articular cartilage and reparative fibrocartilage
      tissue. Separation occurred at either the deep articular cartilage or the
      subchondral bone, with the former being dominant in the early OCD lesions. The
      present results suggest that the primary pathological changes in OCD of the elbow
      were due to damage of articular cartilage induced by repeated stress following
      degenerative and reparative process of articular cartilage and subchondral
      fracturing, and separation subsequently occurred on the cartilage and developed
      onto the subchondral bone in its advanced stages.

PMID- 16984618
TI  - Pure non-gestational choriocarcinoma of the ovary diagnosed by DNA polymorphism
      analysis.
AB  - Pure primary ovarian choriocarcinoma is a rare condition that can be of
      gestational or non-gestational origin. Non-gestational choriocarcinoma has been
      found to be resistant to single-agent chemotherapy and has a worse prognosis than
      gestational choriocarcinoma, but it is difficult to distinguish the two types by
      routine histological examination. Herein is reported a case of primary pure non
      gestational choriocarcinoma of the ovary in a 33-year-old nulligravid woman, as
      confirmed by DNA polymorphism analysis. All tested microsatellite markers had
      identical DNA profiles with the same allelic sizes between the tumor and the
      myometrium of the patient, who was homozygous for three markers (BAT26, BAT25 and
      D17S250) and heterozygous for four (D2S123, D18S57, DCC and D18S58), supporting
      non-gestational origin. The patient has no evidence of disease 17 months after
      surgery and four cycles of combination chemotherapy. This case demonstrates the
      usefulness of DNA polymorphism analysis for the determination of the origin of
      extrauterine choriocarcinoma. Clinical relevance of this method needs to be
      further studied and substantiated.

PMID- 16984619
TI  - Distinct expression of Kaposi's sarcoma-associated herpesvirus-encoded proteins
      in Kaposi's sarcoma and multicentric Castleman's disease.
AB  - The expression of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)-encoded
      proteins is herein demonstrated in Kaposi's sarcoma (KS) and multicentric
      Castleman's disease (MCD) in a single lymph node derived from a patient with
      acquired immunodeficiency syndrome. Immunohistochemistry revealed that both lytic
      and latent KSHV proteins were expressed in cells of the MCD lesion. KSHV-encoded
      viral interleukin-6 was also detected in follicular dendritic cells of the
      germinal center. Cytoplasmic localization of open reading frame 59 protein and
      latency-associated nuclear antigen suggested KSHV activation in the MCD lesion.
      Moreover, a high copy number of KSHV was detected in the blood. Clinically,
      pegylated-liposomal doxorubicin induced regression of not only KS, but also
      lymphadenopathy of the MCD lesion with a decrease in KSHV load and human
      interleukin-6 in the blood. To the best of the authors' knowledge this is the
      first case demonstrating differential expression of virus proteins in two KSHV
      associated diseases, KS and MCD, in the same section. The case confirms lytic
      KSHV infection in MCD, and suggests that clinical symptoms of MCD might be
      closely linked with KSHV activation.

PMID- 16984620
TI  - Inflammatory myofibroblastic tumor of the uterus with prominent myxoid change.
AB  - A surgical case of inflammatory myofibroblastic tumor arising in the uterine
      corpus and exhibiting prominent myxoid change of the stroma is reported. The
      patient was a 63-year-old woman with a large tumor mass that filled the uterine
      cavity and measured 11 cm in maximal dimension. The tumor had a gelatinous
      appearance and consisted of a loose proliferation of stellate or polygonal cells
      on a myxomatous background. Fascicular proliferation of spindle cells was also
      observed focally, and a chronic inflammatory cell infiltration was seen in many
      areas. Tumor cells had mild atypism and were immunoreactive for vimentin, alpha
      smooth muscle actin, and anaplastic lymphoma kinase (ALK). Focal immunoreactivity
      for high-molecular-weight caldesmon (h-caldesmon) was also noted. The patient has
      been free from recurrence for 8 months. Inflammatory myofibroblastic tumor of the
      uterus occasionally shows prominent myxoid change of the stroma, and
      differentiation from myxoid leiomyosarcoma is problematic in these cases. Based
      on the immunoreactivity of tumor cells for ALK and h-caldesmon, the present tumor
      was considered inflammatory myofibroblastic tumor showing a focal phenotypic
      transition from myofibroblasts to smooth muscle cells.

PMID- 16984621
TI  - Heterotopic intrathymic thyroid tissue.
AB  - Heterotopic intrathymic thyroid tissue is an extremely rare condition, but it is
      important to distinguish it from metastases of clinically undetected thyroid
      carcinoma because metastatic papillary thyroid carcinoma is often so well
      differentiated, simulating normal thyroid tissue. Described herein are
      histological findings of heterotopic intrathymic thyroid tissue that was
      incidentally identified in a woman with papillary thyroid carcinoma during
      histological examination of a radical neck dissection specimen. These findings
      emphasize that this rare incidence may occur and should be differentiated from
      metastatic papillary carcinoma. Histologically, the patient's intrathymic thyroid
      follicles were identical to the normal thyroid follicles, having flat cuboidal
      cells with uniformly small nuclei without nuclear grooves or inclusions. The
      follicular cells had a low Ki-67 labeling index close to zero, and
      immunonegativity for galectin-3, HBME-1, and RET oncoprotein, in contrast to the
      tumor cells in primary papillary thyroid carcinoma of the patient. To the
      authors' knowledge this is the first case report of intrathymic heterotopic
      thyroid tissue posing a diagnostic difficulty in a patient with papillary thyroid
      carcinoma.

PMID- 16984622
TI  - Pancreatic acinar cell carcinoma extending into the common bile and main
      pancreatic ducts.
AB  - Acinar cell carcinoma (ACC) of the pancreas is relatively rare, accounting for
      only approximately 1% of all exocrine pancreatic tumors. A 69-year-old man was
      found to have a mass lesion measuring approximately 4 cm in diameter in the
      pancreatic head on ultrasound, abdominal dynamic CT, and percutaneous
      transhepatic cholangiography. Magnetic resonance cholangiopancreatography showed
      defect of the lower common bile duct (CBD) due to obstruction by the tumor cast.
      Histopathologically, the pancreatic head tumor invaded the main pancreatic duct
      (MPD) and CBD with extension into the CBD in a form of tumor cast. The tumor
      cells consisted of a solid proliferation with abundant eosinophilic cytoplasm and
      round nuclei in an acinar and trabecular fashion. A 55-year-old man with upper
      abdominal pain and nausea, had a cystic lesion approximately 3 cm in size in the
      pancreatic tail on CT. Histopathologically, the tumor was encapsulated by fibrous
      capsule and had extensive central necrosis with solid areas in the tumor
      periphery, and invaded with extension into the MPD in a form of tumor cast. The
      tumor cells resembled acinar cells in solid growths. Two resected cases of ACC
      with unusual tumor extension into the CBD and the MPD, respectively, are
      reported.

PMID- 16984623
TI  - Retroperitoneal lipomatous angiomyolipoma associated with amyloid deposition
      masquerading as well-differentiated liposarcoma.
AB  - Reported herein is a case of retroperitoneal angiomyolipoma associated with
      amyloid deposition, masquerading as well-differentiated liposarcoma. A 16 x 13 cm
      lipomatous tumor was resected from the perirenal retroperitoneum of a 71-year-old
      woman. Microscopically, the tumor was exclusively composed of mature adipose
      tissue and abnormal thick blood vessels, but bundles of smooth muscle were
      lacking. In addition, amyloid was deposited between fat cells. Initially, well
      differentiated liposarcoma was highly suspected. However, there were a few
      epithelioid cells with clear vacuolated cytoplasm within the vessel walls, which
      were immunoreactive for smooth muscle markers and HMB-45. Real-time polymerase
      chain reaction failed to demonstrate the amplification of the murine double
      minute type 2 gene and cyclin-dependent kinase 4 gene in this tumor. Therefore,
      the tumor was diagnosed as lipomatous angiomyolipoma. After the diagnosis, it was
      found that the patient had multiple myeloma and cardiac amyloidosis, suggesting
      that the amyloid deposition within the tumor was a complication of the myeloma.
      Lipomatous angiomyolipoma may be a diagnostic pitfall of retroperitoneal
      lipomatous tumors.

PMID- 16984624
TI  - Primary myxoid solitary fibrous tumor involving the seminal vesicle.
AB  - Although focal myxoid change is a well-recognized feature of solitary fibrous
      tumor (SFT), predominantly myxoid SFT are exceedingly rare. Reported herein is
      the case of a 65-year-old man with SFT containing abundant myxoid matrix, arising
      from the capsule of the right seminal vesicle. To the authors' knowledge this is
      the first myxoid SFT involving the male genito-urinary system. Recognition of the
      myxoid variant of SFT is crucial, given possible confusion with a variety of
      myxoid spindle cell neoplasms with different biological potential in the pelvic
      cavity.

PMID- 16984625
TI  - Recurrent primary cutaneous large B-cell lymphoma after a long-term remission.

PMID- 16984626
TI  - Evaluation of 17-mm St. Jude Medical Regent prosthetic aortic heart valves by
      rest and dobutamine stress echocardiography.
AB  - BACKGROUND: The prosthesis used for aortic valve replacement in patients with
      small aortic root can be too small in relation to body size, thus showing high
      transvalvular gradients at rest and/or under stress conditions. This study was
      carried out to evaluate rest and Dobutamine stress echocardiography (DSE)
      hemodynamic response of 17-mm St. Jude Medical Regent (SJMR-17 mm) in relatively
      aged patients at mean 24 months follow-up. METHODS AND RESULTS: The study
      population consisted of 19 patients (2 men, 17 women, mean age 69.2 +/- 7.3
      years). All patients underwent rest Doppler echocardiography before and after
      surgery and basal and DSE at follow up (infused at rate of 5 microg/Kg/min and
      increased by 5 microg/Kg/min at 5 min intervals up to 40 microg/Kg/min). The
      following parameters were evaluated at rest and/or under DSE: heart rate (HR),
      ejection fraction (EF), cardiac output (CO), peak and mean velocity and pressure
      gradients (MxV, MnV, MxPG, MnPG), effective orifice area (EOA), indexed EOA
      (EOAi), left ventricular mass (LVM), indexed LVM (LVMi), Velocity Time Integral
      at left ventricular outflow tract (VTI LVOT) and transvalvular (Aortic VTI),
      Doppler velocity index (DVI). At rest MxPG and MnPG were 29.2 +/- 7.1 and 16.6 +/
      5.8 mmHg, respectively; EOA and EOAi resulted 1.14 +/- 0.3 cm(2) and 0.76 +/-
      0.2 cm(2)/m(2); DVI was normal (0.50 +/- 0.1). At follow-up LVM and LVMi
      decreased significantly from pre-operative value of 258 +/- 43 g and 157.4 +/-
      27.7 g/m(2) to 191 +/- 23.8 g and 114.5 +/- 10.6 g/m(2), respectively. DSE
      increased significantly HR, CO, EF, MxGP (up to 83.4 +/- 2 1.9 mmHg), MnPG (up to
      43.2 +/- 12.7 mmHg). EOA, EOAi, DVI increased insignificantly (from baseline up
      to 1.2 +/- 0.4 cm(2), 0.75 +/- 0.3 cm(2)/m(2) and 0.48 +/- 0.1 respectively). Two
      patients developed significant intraventricular gradients. CONCLUSION: These data
      show that SJMR 17-mm prostheses can be safely implanted in aortic position in
      relatively aged patients, offering a satisfactory hemodynamic performance at rest
      and under DSE, with full utilization of its available orifice, suggesting that a
      possible mild prosthesis-patient mismatch is not an issue of clinical relevance
      when this small prosthesis is used. Rest and Dobutamine stress echocardiography
      is a useful and effective means for evaluating prosthesis hemodynamics and for
      monitoring the expected LVH regression.

PMID- 16984627
TI  - Tuberculosis chemotherapy: current drug delivery approaches.
AB  - Tuberculosis is a leading killer of young adults worldwide and the global scourge
      of multi-drug resistant tuberculosis is reaching epidemic proportions. It is
      endemic in most developing countries and resurgent in developed and developing
      countries with high rates of human immunodeficiency virus infection. This article
      reviews the current situation in terms of drug delivery approaches for
      tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and
      various other carrier-based drug delivery systems incorporating the principal
      anti-tuberculosis agents have been fabricated that either target the site of
      tuberculosis infection or reduce the dosing frequency with the aim of improving
      patient outcomes. These developments in drug delivery represent attractive
      options with significant merit, however, there is a requisite to manufacture an
      oral system, which directly addresses issues of unacceptable rifampicin
      bioavailability in fixed-dose combinations. This is fostered by the need to
      deliver medications to patients more efficiently and with fewer side effects,
      especially in developing countries. The fabrication of a polymeric once-daily
      oral multiparticulate fixed-dose combination of the principal anti-tuberculosis
      drugs, which attains segregated delivery of rifampicin and isoniazid for improved
      rifampicin bioavailability, could be a step in the right direction in addressing
      issues of treatment failure due to patient non-compliance.

PMID- 16984628
TI  - The transcription factor ATF3 is upregulated during chondrocyte differentiation
      and represses cyclin D1 and A gene transcription.
AB  - BACKGROUND: Coordinated chondrocyte proliferation and differentiation are
      required for normal endochondral bone growth. Transcription factors binding to
      the cyclicAMP response element (CRE) are known to regulate these processes. One
      member of this family, Activating Transcription Factor 3 (ATF3), is expressed
      during skeletogenesis and acts as a transcriptional repressor, but the function
      of this protein in chondrogenesis is unknown. RESULTS: Here we demonstrate that
      Atf3 mRNA levels increase during mouse chondrocyte differentiation in vitro and
      in vivo. In addition, Atf3 mRNA levels are increased in response to cytochalasin
      D treatment, an inducer of chondrocyte maturation. This is accompanied by
      increased Atf3 promoter activity in cytochalasin D-treated chondrocytes. We had
      shown earlier that transcription of the cell cycle genes cyclin D1 and cyclin A
      in chondrocytes is dependent on CREs. Here we demonstrate that overexpression of
      ATF3 in primary mouse chondrocytes results in reduced transcription of both
      genes, as well as decreased activity of a CRE reporter plasmid. Repression of
      cyclin A transcription by ATF3 required the CRE in the cyclin A promoter. In
      parallel, ATF3 overexpression reduces the activity of a SOX9-dependent promoter
      and increases the activity of a RUNX2-dependent promoter. CONCLUSION: Our data
      suggest that transcriptional induction of the Atf3 gene in maturing chondrocytes
      results in down-regulation of cyclin D1 and cyclin A expression as well as
      activation of RUNX2-dependent transcription. Therefore, ATF3 induction appears to
      facilitate cell cycle exit and terminal differentiation of chondrocytes.

PMID- 16984629
TI  - Measles transmission following the tsunami in a population with a high one-dose
      vaccination coverage, Tamil Nadu, India 2004-2005.
AB  - BACKGROUND: On 26 December 2004, a tsunami struck the coast of the state of Tamil
      Nadu, India, where one-dose measles coverage exceeded 95%. On 29 December,
      supplemental measles immunization activities targeted children 6 to 60 months of
      age in affected villages. On 30 December, Cuddalore, a tsunami-affected district
      in Tamil Nadu reported a cluster of measles cases. We investigated this cluster
      to estimate the magnitude of the problem and to propose recommendations for
      control. METHODS: We received notification of WHO-defined measles cases through
      stimulated passive surveillance. We collected information regarding date of
      onset, age, sex, vaccination status and residence. We collected samples for IgM
      antibodies and genotype studies. We modeled the accumulation of susceptible
      individuals over the time on the basis of vaccination coverage, vaccine efficacy
      and birth rate. RESULTS: We identified 101 measles cases and detected IgM
      antibodies against measles virus in eight of 11 sera. Cases were reported from
      tsunami-affected (n = 71) and unaffected villages (n = 30) with attack rates of
      1.3 and 1.7 per 1000, respectively. 42% of cases in tsunami-affected villages had
      an onset date within 14 days of the tsunami. The median ages of case-patients in
      tsunami-affected and un-affected areas were 54 months and 60 months respectively
      (p = 0.471). 36% of cases from tsunami-affected areas were above 60 months of
      age. Phylogenetic analyses indicated that the sequences of virus belonged to
      genotype D8 that circulated in Tamil Nadu. CONCLUSION: Measles virus circulated
      in Cuddalore district following the tsunami, although there was no association
      between the two events. Transmission despite high one-dose vaccination coverage
      pointed to the limitations of this vaccination strategy. A second opportunity for
      measles immunization may help reducing measles mortality and morbidity in such
      areas. Children from 6 month to 14 years of age must be targeted for supplemental
      immunization during complex emergencies.

PMID- 16984630
TI  - Breast cancer risk factor knowledge among nurses in teaching hospitals of
      Karachi, Pakistan: a cross-sectional study.
AB  - BACKGROUND: Breast cancer is the most common cancer among women in both the
      developed and the developing world. The incidence of breast cancer in Karachi,
      Pakistan is 69.1 per 100,000 with breast cancer presentation in stages III and IV
      being common (>or= 50%). The most pragmatic solution to early detection lies in
      breast cancer education of women. Nurses constitute a special group having
      characteristics most suited for disseminating breast cancer information to the
      women. We assessed the level of knowledge of breast cancer risk factors among
      registered female nurses in teaching hospitals of Karachi. We also identified
      whether selected factors among nurses were associated with their knowledge of
      breast cancer risk factors, so that relevant measures to improve knowledge of
      nurses could be implemented. METHODS: A cross-sectional survey was conducted in
      seven teaching hospitals of Karachi using stratified random sampling with
      proportional allocation. A total of 609 registered female nurses were interviewed
      using a structured questionnaire adapted from the Stager's Comprehensive Breast
      Cancer Knowledge Test. Knowledge of breast cancer risk factors was categorized
      into good, fair and poor categories. Ordinal regression was used to identify
      factors associated with risk knowledge among nurses. RESULTS: Thirty five percent
      of nurses had good knowledge of risk factors. Graduates from private nursing
      schools (aOR = 4.23, 95% CI: 2.93, 6.10), nurses who had cared for breast cancer
      patients (aOR = 1.41, 95% CI: 1.00, 1.99), those having received a breast
      examination themselves (aOR = 1.56, 95% CI: 1.08, 2.26) or those who ever
      examined a patient's breast (aOR = 1.87, 95% CI: 1.34, 2.61) were more likely to
      have good knowledge. CONCLUSION: A relatively small proportion of the nursing
      population had good level of knowledge of the breast cancer risk factors. This
      knowledge is associated with nursing school status, professional breast cancer
      exposure and self history of clinical breast examination. Since only about one
      third of the nurses had good knowledge about risk factors, there is a need to
      introduce breast cancer education in nursing schools particularly in the public
      sector. Continuing nursing education at the workplace can be of additional
      benefit.

PMID- 16984631
TI  - Use of the lambda Red recombinase system to produce recombinant prophages
      carrying antibiotic resistance genes.
AB  - BACKGROUND: The Red recombinase system of bacteriophage lambda has been used to
      inactivate chromosomal genes in E. coli K-12 through homologous recombination
      using linear PCR products. The aim of this study was to induce mutations in the
      genome of some temperate Shiga toxin encoding bacteriophages. When phage genes
      are in the prophage state, they behave like chromosomal genes. This enables
      marker genes, such as antibiotic resistance genes, to be incorporated into the
      stx gene. Once the phages' lytic cycle is activated, recombinant Shiga toxin
      converting phages are produced. These phages can transfer the marker genes to the
      bacteria that they infect and convert. As the Red system's effectiveness
      decreased when used for our purposes, we had to introduce significant variations
      to the original method. These modifications included: confirming the stability of
      the target stx gene increasing the number of cells to be transformed and using a
      three-step PCR method to produce the amplimer containing the antibiotic
      resistance gene. RESULTS: Seven phages carrying two different antibiotic
      resistance genes were derived from phages that are directly involved in the
      pathogenesis of Shiga toxin-producing strains, using this modified protocol.
      CONCLUSION: This approach facilitates exploration of the transduction processes
      and is a valuable tool for studying phage-mediated horizontal gene transfer.

PMID- 16984632
TI  - Quantification of the variation in percentage identity for protein sequence
      alignments.
AB  - BACKGROUND: Percentage Identity (PID) is frequently quoted in discussion of
      sequence alignments since it appears simple and easy to understand. However,
      although there are several different ways to calculate percentage identity and
      each may yield a different result for the same alignment, the method of
      calculation is rarely reported. Accordingly, quantification of the variation in
      PID caused by the different calculations would help in interpreting PID values in
      the literature. In this study, the variation in PID was quantified systematically
      on a reference set of 1028 alignments generated by comparison of the protein
      three-dimensional structures. Since the alignment algorithm may also affect the
      range of PID, this study also considered the effect of algorithm, and the
      combination of algorithm and PID method. RESULTS: The maximum variation in PID
      due to the calculation method was 11.5% while the effect of alignment algorithm
      on PID was up to 14.6% across three popular alignment methods. The combined
      effect of alignment algorithm and PID calculation gave a variation of up to 22%
      on the test data, with an average of 5.3% +/- 2.8% for sequence pairs with < 30%
      identity. In order to see which PID method was most highly correlated with
      structural similarity, four different PID calculations were compared to
      similarity scores (Sc) from the comparison of the corresponding protein three
      dimensional structures. The highest correlation coefficient for a PID calculation
      was 0.80. In contrast, the more sophisticated Z-score calculated by reference to
      randomized sequences gave a correlation coefficient of 0.84. CONCLUSION: Although
      it is well known amongst expert sequence analysts that PID is a poor score for
      discriminating between protein sequences, the apparent simplicity of the
      percentage identity score encourages its widespread use in establishing cutoffs
      for structural similarity. This paper illustrates that not only is PID a poor
      measure of sequence similarity when compared to the Z-score, but that there is
      also a large uncertainty in reported PID values. Since better alternatives to PID
      exist to quantify sequence similarity, these should be quoted where possible in
      preference to PID. The findings presented here should prove helpful to those new
      to sequence analysis, and in warning those who seek to interpret the value of a
      PID reported in the literature.

PMID- 16984633
TI  - Coding limits on the number of transcription factors.
AB  - BACKGROUND: Transcription factor proteins bind specific DNA sequences to control
      the expression of genes. They contain DNA binding domains which belong to several
      super-families, each with a specific mechanism of DNA binding. The total number
      of transcription factors encoded in a genome increases with the number of genes
      in the genome. Here, we examined the number of transcription factors from each
      super-family in diverse organisms. RESULTS: We find that the number of
      transcription factors from most super-families appears to be bounded. For
      example, the number of winged helix factors does not generally exceed 300, even
      in very large genomes. The magnitude of the maximal number of transcription
      factors from each super-family seems to correlate with the number of DNA bases
      effectively recognized by the binding mechanism of that super-family. Coding
      theory predicts that such upper bounds on the number of transcription factors
      should exist, in order to minimize cross-binding errors between transcription
      factors. This theory further predicts that factors with similar binding sequences
      should tend to have similar biological effect, so that errors based on mis
      recognition are minimal. We present evidence that transcription factors with
      similar binding sequences tend to regulate genes with similar biological
      functions, supporting this prediction. CONCLUSION: The present study suggests
      limits on the transcription factor repertoire of cells, and suggests coding
      constraints that might apply more generally to the mapping between binding sites
      and biological function.

PMID- 16984634
TI  - Can care of elderly be measured? A method for estimating the individual care of
      recipients in community health care.
AB  - BACKGROUND: Almost every country in the Western world has great difficulties
      allocating enough financial resources to meet the needs in the care of the
      increasing elderly population. The main problem is common to all countries and
      concerns the efforts to meet elderly persons' needs on an individual level while
      still maintaining society's responsibility for distributing justice. The aim of
      this study is to elaborate an instrument for measuring the quality of individual
      care and staff's working time in order to allocate public resources fairly. The
      present study gives an account of a new classification system named TiC (Time in
      Care), indicating how it can be used most effectively and also investigating the
      validity and reliability of the system. METHODS: All recipients in 13 sheltered
      homes for elderly care (n = 505) in a Swedish municipality were surveyed
      regarding the care they needed, in dimensions of General Care, Medical Care,
      Cognitive Dysfunction and Rehabilitation, and the time required. Construct
      validity was assessed by means of factor analysis. The inter-rater agreement of
      two raters concerning 79 recipients was measured using weighted Kappa. The
      stability of the instrument and its sensitivity to change were investigated
      through test-retest reliability measurements, conducted once a month during a six
      month period. The content validity of the instrument was also assessed. RESULTS:
      Factor analysis resulted in a reduction of the number of items from 25 to 16 in
      three dimensions: General Care, Medical Care and Cognitive Dysfunction. The Kappa
      analysis showed satisfactory to excellent inter-rater agreement. The care need
      scores were basically stable but showed sensitivity to change in health status.
      CONCLUSION: The instrument was found to be useful and reliable for assessing
      individual needs in community health care.

PMID- 16984635
TI  - Novel insights in the regulation of CCL18 secretion by monocytes and dendritic
      cells via cytokines, toll-like receptors and rheumatoid synovial fluid.
AB  - BACKGROUND: The T cell attracting chemokine CCL18 is produced by antigen
      presenting cells and a role for CCL18 has been suggested in the pathogenesis of a
      variety of diseases. Rheumatoid arthritis (RA) is one of these conditions, in
      which abundant CCL18 production is present. Although Th2 cytokines and IL-10 are
      known to have an effect on CCL18 production, there are several gaps in our
      knowledge regarding the exact regulation of CCL18 secretion, both in general and
      in RA. In this study we provide new insights in the regulation of CCL18 secretion
      by monocytes and dendritic cells. RESULTS: In contrast to a large panel of pro
      inflammatory stimuli (IL-1beta, TNF-alpha, IL-10, IL-13, IL-15, IL-17, IL-18, IFN
      gamma), T cell mimicking molecules (RANKL, CD40L) or TLR driven maturation, the
      anti-inflammatory IL-10 strongly stimulated DC to secrete CCL18. On freshly
      isolated monocytes, CCL18 secretion was induced by IL-4 and IL-13, in strong
      synergy with IL-10. This synergistic effect could already be observed after only
      24 hours, indicating that not only macrophages and dendritic cells, but also
      monocytes secrete CCL18 under these stimulatory conditions. A high CCL18
      expression was detected in RA synovial tissue and incubation of monocytes with
      synovial fluid from RA patients clearly enhanced the effects of IL-4, IL-13 and
      IL-10. Surprisingly, the effect of synovial fluid was not driven by IL-10 of IL
      13, suggesting the presence of another CCL18 inducing factor in synovial fluid.
      CONCLUSION: In summary, IL-10 synergistically induces CCL18 secretion in
      combination with IL-4 of IL-13 on monocytes and monocyte derived cells. The
      effects of IL-14, IL-13 and IL-10 are strongly enhanced by synovial fluid. This
      synergy may contribute to the high CCL18 expression in RA.

PMID- 16984636
TI  - Conducting research in individual patients: lessons learnt from two series of N
      of-1 trials.
AB  - BACKGROUND: Double-blind randomised N-of-1 trials (N-of-1 trials) may help with
      decisions concerning treatment when there is doubt regarding the effectiveness
      and suitability of medication for individual patients. The patient is his or her
      own control, and receives the experimental and the control treatment during
      several periods of time in random order. Reports of N-of-1 trials are still
      relatively scarce, and the research methodology is not as firmly established as
      that of RCTs. Recently, we have conducted two series of N-of-1 trials in general
      practice. Before, during, and after data-collection, difficulties regarding
      outcome assessment, analysis of the results, the withdrawal of patients, and the
      follow-up had to be dealt with. These difficulties are described and our
      solutions are discussed. DISCUSSION: To prevent or anticipate difficulties in N
      of-1 trials, we argue that that it is important to individualize the outcome
      measures, and to carefully consider the objective, type of randomisation and the
      analysis. It is recommended to use the same dosages and dosage forms that the
      patient used before the trial, to start the trial with a run-in period, to
      formulate both general and individualized decision rules regarding the efficacy
      of treatment, to adjust treatment policies immediately after the trial, and to
      provide adequate instructions and support if treatment is adjusted. SUMMARY:
      Because of the specific characteristics of N-of-1 trials it is difficult to
      formulate general 'how to do it' guidelines for designing N-of-1 trials. However,
      when the design of each N-of-1 trial is tailored to the specific characteristics
      of each individual patient and the underlying medical problem, most difficulties
      in N-of-1 trials can be prevented or overcome. In this way, N-of-1 trials may be
      of help when deciding on drug treatment for individual patients.

PMID- 16984637
TI  - Schizophrenia and quality of life: a one-year follow-up in four EU countries.
AB  - BACKGROUND: This article systematically monitors the quality of life (QOL) of
      patients with schizophrenia from seven different sites across four European
      countries: France, Ireland, Portugal and Spain. METHODS: A one-year prospective
      cohort study was carried out. Inclusion criteria for patients were: a clinical
      lifetime diagnosis of schizophrenia according to ICD-10 (F20) diagnostic criteria
      for research, age between 18 and 65 years and at least one contact with mental
      health services in 1993. Data concerning QOL were recorded in seven sites from
      four countries: France, Portugal, Ireland and Spain, and were obtained using the
      Baker and Intagliata scale. At baseline, 339 patients answered the QOL
      questionnaire. At one-year follow-up, Spain could not participate, so only 263
      patients were contacted and 219 agreed to take part. QOL was compared across
      centres by areas and according to a global index. QOL was correlated with
      presence of clinical and social problems, needs for care and interventions
      provided during the one-year follow-up. RESULTS: We did not find any link between
      gender and QOL. There were some significant differences between centres
      concerning many items. What is more, these differences were relative: in Lisbon
      where the lowest level of satisfaction was recorded, people were satisfied with
      food but highly dissatisfied with finances, whereas in St Etienne, where the
      highest level of satisfaction was recorded, people were less satisfied with food
      when they were more satisfied with finances. The evolution in one year among
      those respondents who took part in the follow-up (excluding the subjects from
      Granada) showed different patterns depending on the items. CONCLUSION: The four
      countries have different resources and patients live in rather different
      conditions. However, the main differences as far as their QOL is concerned very
      much depend on extra-psychiatric variables, principally marital status and
      income.

PMID- 16984638
TI  - Life satisfaction and resilience in medical school--a six-year longitudinal,
      nationwide and comparative study.
AB  - BACKGROUND: This study examined the relationship between life satisfaction among
      medical students and a basic model of personality, stress and coping. Previous
      studies have shown relatively high levels of distress, such as symptoms of
      depression and suicidal thoughts in medical undergraduates. However despite the
      increased focus on positive psychological health and well-being during the past
      decades, only a few studies have focused on life satisfaction and coping in
      medical students. This is the first longitudinal study which has identified
      predictors of sustained high levels of life satisfaction among medical students.
      METHODS: This longitudinal, nationwide questionnaire study examined the course of
      life satisfaction during medical school, compared the level of satisfaction of
      medical students with that of other university students, and identified
      resilience factors. T-tests were used to compare means of life satisfaction
      between and within the population groups. K-means cluster analyses were applied
      to identify subgroups among the medical students. Analysis of Variance (ANOVA)
      and logistic regression analyses were used to compare the subgroups. RESULTS:
      Life satisfaction decreased during medical school. Medical students were as
      satisfied as other students in the first year of study, but reported less
      satisfaction in their graduation year. Medical students who sustained high levels
      of life satisfaction perceived medical school as interfering less with their
      social and personal life, and were less likely to use emotion focused coping,
      such as wishful thinking, than their peers. CONCLUSION: Medical schools should
      encourage students to spend adequate time on their social and personal lives and
      emphasise the importance of health-promoting coping strategies.

PMID- 16984639
TI  - Evaluation of efalizumab using safe psoriasis control.
AB  - BACKGROUND: Safe Psoriasis Control (SPC) is an important comprehensive measure
      that is validated for the assessment of benefit:risk of psoriasis treatments,
      combining efficacy, quality of life, and safety measures. The objective of this
      analysis was to assess the benefit:risk of efalizumab, a novel biologic agent
      indicated for the treatment of moderate-to-severe plaque psoriasis, by applying
      the SPC to data from randomized, placebo-controlled clinical studies of
      efalizumab. METHODS: SPC was applied to week 12 data from four placebo
      controlled, Phase III studies: three retrospective and one prospective, the
      latter including a cohort of "high-need" patients for whom existing therapies
      were inadequate or unsuitable. RESULTS: In the retrospective analysis, 39.4% of
      patients achieved SPC after 12 weeks of treatment with efalizumab, compared with
      10.4% for placebo. In the prospective analysis, 34.3% of patients achieved SPC
      after 12 weeks of treatment with efalizumab, compared with 7.3% on placebo. Among
      high-need patients, 33.0% achieved SPC, compared with 3.4% on placebo.
      CONCLUSION: Efalizumab has a favorable benefit:risk profile using the
      comprehensive outcome measure SPC.

PMID- 16984640
TI  - Frequency and patterns of early recanalization after vasectomy.
AB  - BACKGROUND: Our understanding of early post-vasectomy recanalization is limited
      to histopathological studies. The objective of this study was to estimate the
      frequency and to describe semen analysis patterns of early recanalization after
      vasectomy. METHODS: Charts displaying serial post-vasectomy semen analyses were
      created using the semen analysis results from 826 and 389 men participating in a
      randomized trial of fascial interposition (FI) and an observational study of
      cautery, respectively. In the FI trial, participants were randomly allocated to
      vas occlusion by ligation and excision with or without FI. In the cautery study,
      sites used their usual cautery occlusion technique, two with and two without FI.
      Presumed early recanalization was based on the assessment of individual semen
      analysis charts by three independent reviewers. Discrepancies were resolved by
      consensus. RESULTS: Presumed early recanalization was characterized by a very low
      sperm concentration within two weeks after vasectomy followed by return to large
      numbers of sperm over the next few weeks. The overall proportion of men with
      presumed early recanalization was 13% (95% CI 12%-15%). The risk was highest with
      ligation and excision without FI (25%) and lowest for thermal cautery with FI
      (0%). The highest proportion of presumed early recanalization was observed among
      men classified as vasectomy failures. CONCLUSION: Early recanalization, occurring
      within the first weeks after vasectomy, is more common than generally recognized.
      Its frequency depends on the occlusion technique performed.

PMID- 16984641
TI  - Selection of reference genes for quantitative RT-PCR studies in striped dolphin
      (Stenella coeruleoalba) skin biopsies.
AB  - BACKGROUND: Odontocete cetaceans occupy the top position of the marine food-web
      and are particularly sensitive to the bioaccumulation of lipophilic contaminants.
      The effects of environmental pollution on these species are highly debated and
      various ecotoxicological studies have addressed the impact of xenobiotic
      compounds on marine mammals, raising conservational concerns. Despite its
      sensitivity, quantitative real-time PCR (qRT-PCR) has never been used to quantify
      gene induction caused by exposure of cetaceans to contaminants. A limitation for
      the application of qRT-PCR is the need for appropriate reference genes which
      allow the correct quantification of gene expression. A systematic evaluation of
      potential reference genes in cetacean skin biopsies is presented, in order to
      validate future qRT-PCR studies aiming at using the expression of selected genes
      as non-lethal biomarkers. RESULTS: Ten commonly used housekeeping genes (HKGs)
      were partially sequenced in the striped dolphin (Stenella coeruleoalba) and, for
      each gene, PCR primer pairs were specifically designed and tested in qRT-PCR
      assays. The expression of these potential control genes was examined in 30
      striped dolphin skin biopsy samples, obtained from specimens sampled in the north
      western Mediterranean Sea. The stability of selected control genes was determined
      using three different specific VBA applets (geNorm, NormFinder and BestKeeper)
      which produce highly comparable results. Glyceraldehyde-3P-dehydrogenase (GAPDH)
      and tyrosine 3-monooxygenase (YWHAZ) always rank as the two most stably expressed
      HKGs according to the analysis with geNorm and Normfinder, and are defined as
      optimal control genes by BestKepeer. Ribosomal protein L4 (RPL4) and S18 (RPS18)
      also exhibit a remarkable stability of their expression levels. On the other
      hand, transferrin receptor (TFRC), phosphoglycerate kinase 1 (PGK1), hypoxanthine
      ribosyltransferase (HPRT1) and beta-2-microglobin (B2M) show variable expression
      among the studied samples and appear as less suitable reference genes for data
      normalization. CONCLUSION: In this work, we have provided essential background
      information for the selection of control genes in qRT-PCR studies of cetacean
      skin biopsies, as a molecular technique to investigate ecotoxicological hazard in
      marine mammals. Of 10 HKGs tested, those encoding for YWHAZ and GAPDH appear as
      the most reliable control genes for the normalization of qRT-PCR data in the
      analysis of striped dolphin skin biopsies. Potentially useful reference genes are
      also those encoding for ribosomal proteins L4 and S18.

PMID- 16984642
TI  - Knee loading stimulates cortical bone formation in murine femurs.
AB  - BACKGROUND: Bone alters its architecture and mass in response to the mechanical
      environment, and thus varying loading modalities have been examined for studying
      load-driven bone formation. The current study aimed to evaluate the anabolic
      effects of knee loading on diaphyseal cortical bone in the femur. METHODS: Using
      a custom-made piezoelectric loader, 0.5-N loads were laterally applied to the
      left knee of C57/BL/6 mice at 5, 10, 15, and 20 Hz for 3 minutes per day for 3
      consecutive days. Animals were sacrificed for examination 13 days after the last
      loading. The contralateral femur was used as a non-loading control, and the
      statistical significance of loading effects was evaluated with p < 0.05. RESULTS:
      Although diaphyseal strains were measured as small as 12 mustrains, bone
      histomorphometry clearly demonstrated frequency-dependent enhancement of bone
      formation. Compared to a non-loading control, bone formation on the periosteal
      surface was significantly enhanced. The loading at 15 Hz was most effective in
      elevating the mineralizing surface (1.7 x; p < 0.05), mineral apposition rate
      (1.4 x; p < 0.001), and bone formation rate (2.4 x; p < 0.01). The loading at 10
      Hz elevated the mineralizing surface (1.4 x; p < 0.05), mineral apposition rate
      (1.3 x; p < 0.01), and bone formation rate (1.8 x; p < 0.05). The cross-sectional
      cortical area and the cortical thickness in the femoral diaphysis were
      significantly increased by loading at 10 Hz (both 9%) and 15 Hz (12% and 13%,
      respectively). CONCLUSION: The results support the anabolic effects of knee
      loading on diaphyseal cortical bone in the femur with small in situ strain, and
      they extend our knowledge on the interplay between bone and joints. Strengthening
      the femur contributes to preventing femoral fractures, and the discovery about
      the described knee loading might provide a novel strategy to strengthen
      osteoporotic bones. Further analyses are required to understand the biophysical
      and molecular mechanism behind knee loading.

PMID- 16984644
TI  - Altered hippocampus synaptic function in selenoprotein P deficient mice.
AB  - Selenium is an essential micronutrient that function through selenoproteins.
      Selenium deficiency results in lower concentrations of selenium and
      selenoproteins. The brain maintains it's selenium better than other tissues under
      low-selenium conditions. Recently, the selenium-containing protein selenoprotein
      P (Sepp) has been identified as a possible transporter of selenium. The targeted
      disruption of the selenoprotein P gene (Sepp1) results in decreased brain
      selenium concentration and neurological dysfunction, unless selenium intake is
      excessive However, the effect of selenoprotein P deficiency on the processes of
      memory formation and synaptic plasticity is unknown. In the present studies
      Sepp1(-/-) mice and wild type littermate controls (Sepp1(+/+)) fed a high
      selenium diet (1 mg Se/kg) were used to characterize activity, motor
      coordination, and anxiety as well as hippocampus-dependent learning and memory.
      Normal associative learning, but disrupted spatial learning was observed in
      Sepp1(-/-) mice. In addition, severe alterations were observed in synaptic
      transmission, short-term plasticity and long-term potentiation in hippocampus
      area CA1 synapses of Sepp1(-/-) mice on a 1 mg Se/kg diet and Sepp1(+/+) mice fed
      a selenium-deficient (0 mg Se/kg) diet. Taken together, these data suggest that
      selenoprotein P is required for normal synaptic function, either through presence
      of the protein or delivery of required selenium to the CNS.

PMID- 16984643
TI  - The ancient Virus World and evolution of cells.
AB  - BACKGROUND: Recent advances in genomics of viruses and cellular life forms have
      greatly stimulated interest in the origins and evolution of viruses and, for the
      first time, offer an opportunity for a data-driven exploration of the deepest
      roots of viruses. Here we briefly review the current views of virus evolution and
      propose a new, coherent scenario that appears to be best compatible with
      comparative-genomic data and is naturally linked to models of cellular evolution
      that, from independent considerations, seem to be the most parsimonious among the
      existing ones. RESULTS: Several genes coding for key proteins involved in viral
      replication and morphogenesis as well as the major capsid protein of icosahedral
      virions are shared by many groups of RNA and DNA viruses but are missing in
      cellular life forms. On the basis of this key observation and the data on
      extensive genetic exchange between diverse viruses, we propose the concept of the
      ancient virus world. The virus world is construed as a distinct contingent of
      viral genes that continuously retained its identity throughout the entire history
      of life. Under this concept, the principal lineages of viruses and related
      selfish agents emerged from the primordial pool of primitive genetic elements,
      the ancestors of both cellular and viral genes. Thus, notwithstanding the
      numerous gene exchanges and acquisitions attributed to later stages of evolution,
      most, if not all, modern viruses and other selfish agents are inferred to descend
      from elements that belonged to the primordial genetic pool. In this pool, RNA
      viruses would evolve first, followed by retroid elements, and DNA viruses. The
      Virus World concept is predicated on a model of early evolution whereby emergence
      of substantial genetic diversity antedates the advent of full-fledged cells,
      allowing for extensive gene mixing at this early stage of evolution. We outline a
      scenario of the origin of the main classes of viruses in conjunction with a
      specific model of precellular evolution under which the primordial gene pool
      dwelled in a network of inorganic compartments. Somewhat paradoxically, under
      this scenario, we surmise that selfish genetic elements ancestral to viruses
      evolved prior to typical cells, to become intracellular parasites once bacteria
      and archaea arrived at the scene. Selection against excessively aggressive
      parasites that would kill off the host ensembles of genetic elements would lead
      to early evolution of temperate virus-like agents and primitive defense
      mechanisms, possibly, based on the RNA interference principle. The emergence of
      the eukaryotic cell is construed as the second melting pot of virus evolution
      from which the major groups of eukaryotic viruses originated as a result of
      extensive recombination of genes from various bacteriophages, archaeal viruses,
      plasmids, and the evolving eukaryotic genomes. Again, this vision is predicated
      on a specific model of the emergence of eukaryotic cell under which archaeo
      bacterial symbiosis was the starting point of eukaryogenesis, a scenario that
      appears to be best compatible with the data. CONCLUSION: The existence of several
      genes that are central to virus replication and structure, are shared by a broad
      variety of viruses but are missing from cellular genomes (virus hallmark genes)
      suggests the model of an ancient virus world, a flow of virus-specific genes that
      went uninterrupted from the precellular stage of life's evolution to this day.
      This concept is tightly linked to two key conjectures on evolution of cells:
      existence of a complex, precellular, compartmentalized but extensively mixing and
      recombining pool of genes, and origin of the eukaryotic cell by archaeo-bacterial
      fusion. The virus world concept and these models of major transitions in the
      evolution of cells provide complementary pieces of an emerging coherent picture
      of life's history. REVIEWERS: W. Ford Doolittle, J. Peter Gogarten, and Arcady
      Mushegian.

PMID- 16984645
TI  - EGF-induced activation of Akt results in mTOR-dependent p70S6 kinase
      phosphorylation and inhibition of HC11 cell lactogenic differentiation.
AB  - BACKGROUND: HC11 mouse mammary epithelial cells differentiate in response to
      lactogenic hormone resulting in expression of milk proteins including beta
      casein. Previous studies have shown that epidermal growth factor (EGF) blocks
      differentiation not only through activation of the Ras/Mek/Erk pathway but also
      implicated phosphatidylinositol-3-kinase (PI-3-kinase) signaling. The current
      study analyzes the mechanism of the PI-3-kinase pathway in an EGF-induced block
      of HC11 lactogenic differentiation. RESULTS: HC11 and HC11-luci cells, which
      contain luciferase gene under the control of a beta-casein promotor, were treated
      with specific chemical inhibitors of signal transduction pathways or transiently
      infected/transfected with vectors encoding dominant negative-Akt (DN-Akt) or
      conditionally active-Akt (CA-Akt). The expression of CA-Akt inhibited lactogenic
      differentiation of HC11 cells, and the infection with DN-Akt adenovirus enhanced
      beta-casein transcription and rescued beta-casein promotor-regulated luciferase
      activity in the presence of EGF. Treatment of cells with Rapamycin, an inhibitor
      of mTOR, blocked the effects of EGF on beta-casein promotor driven luciferase
      activity as effectively as PI-3-kinase inhibitors. While expression of CA-Akt
      caused a constitutive activation of p70S6 kinase (p70S6K) in HC11 cells, the
      inhibition of either PI-3-kinase or mTOR abolished the activation of p70S6K by
      EGF. The activation of p70S6K by insulin or EGF resulted in the phosphorylation
      of ribosomal protein S6 (RPS6), elongation initiation factor 4E (elF4E) and 4E
      binding protein1 (4E-BP1). But lower levels of PI-3-K and mTOR inhibitors were
      required to block insulin-induced phosphorylation of RPS6 than EGF-induced
      phosphorylation, and insulin-induced phosphorylation of elF4E and 4E-BP1 was not
      completely mTOR dependent suggesting some diversity of signaling for EGF and
      insulin. In HC11 cells undergoing lactogenic differentiation the phosphorylation
      of p70S6K completely diminished by 12 hours, and this was partly attributable to
      dexamethasone, a component of lactogenic hormone mix. However, p70S6K
      phosphorylation persisted in the presence of lactogenic hormone and EGF, but the
      activation could be blocked by a PI-3-kinase inhibitor. CONCLUSION: PI-3-kinase
      signaling contributes to the EGF block of lactogenic differentiation via Akt and
      p70S6K. The EGF-induced activation of PI-3-kinase-Akt-mTOR regulates
      phosphorylation of molecules including ribosomal protein S6, eIF4E and 4E-BP1
      that influence translational control in HC11 cells undergoing lactogenic
      differentiation.

PMID- 16984646
TI  - Quantitative expression analysis of HHV-6 cell receptor CD46 on cells of human
      cord blood, peripheral blood and G-CSF mobilised leukapheresis cells.
AB  - Human herpesvirus-6 (HHV-6) can infect blood cells and thereby may inhibit
      hematopoietic stem and progenitor cell expansion and differentiation. In this
      context, it has been discussed if early progenitor cells can be infected by HHV
      6. CD46 was identified as one possible cellular surface receptor for HHV-6. The
      study presented here had been done to get insight into the susceptibility of
      various leukocyte subpopulations to HHV-6 (including early hematopoietic
      progenitors) by determining the amount of CD46 molecules expressed on their
      surfaces. Human cord blood cells, peripheral blood cells and G-CSF mobilised
      progenitor cells were analysed by flow cytometry. CD46 molecule number per cell
      was determined and compared to calibration beads conjugated with known ratio of
      PE per bead. Highest CD46 expression was detected on B- lymphocytes, whereas T
      lymphocytes only showed about half of the amount found on B cells. Hematopoietic
      progenitors also carried CD46 at intermediate levels. Unexpectedly, CD46
      expression on progenitors from G-CSF mobilised leukapheresis products was
      approximately 20% of that found on comparable cells from untreated cord blood. In
      conclusion, hematopoietic progenitor cells express CD46 on their surface, thereby
      fulfilling a basic requirement for the susceptibility of HHV-6 infection.

PMID- 16984647
TI  - Are they really refusing to travel? A qualitative study of prehospital records.
AB  - BACKGROUND: Refusal by the patient to travel after calling an emergency ambulance
      may lead to a preventable waste of scarce resources if it can be shown that an
      alternative more appropriate response could be employed. A greater understanding
      is required of the reasons behind 'refusal to travel' (RTT) in order to find
      appropriate solutions to address this issue. We sought to investigate the reasons
      why patients refuse to travel following emergency call-out in a rural county.
      METHODS: Written records made by ambulance crews for patients (n = 397) who were
      not transported to hospital following an emergency call-out during October 2004
      were retrospectively analysed. RESULTS: Twelve main themes emerged for RTT which
      included non injury or minor injury, falls and recovery after treatment on scene;
      other themes included alternative supervision, follow-up and treatment
      arrangements or patients arranging their own transport. Importantly, only 8% of
      the sample was recorded by ambulance crews as truly refusing to travel against
      advice. CONCLUSION: A system that facilitates standardised recording of RTT
      information including social reasons for non-transportation needs to be designed.
      'Refused to travel' disclaimers need to reflect instances when crew and patient
      are satisfied that not going to hospital is the right outcome. These
      recommendations should be considered within the context of the plans for widening
      the role of ambulance services.

PMID- 16984648
TI  - Port-site tumour recurrence of oral squamous carcinoma following percutaneous
      endoscopic gastrostomy: a lesson to be aware of.
AB  - BACKGROUND: Patients with aero-digestive malignancy will often require a feeding
      gastrostomy during their treatment to maintain their nutritional status. These
      are usually placed percutaneously using an endoscopic technique. CASE
      PRESENTATION: A fifty-six year old male underwent placement of a percutaneous
      gastrostomy (PEG) prior to commencement of his treatment for an oral squamous
      cell carcinoma. The treatment for this was locally curative. However, he
      developed a metastasis at the site of his PEG tube. This was excised en-bloc with
      the anterior gastric and abdominal walls. CONCLUSION: Tumour implantation into
      wounds has been previously reported. In this case the direct trauma of passing
      the PEG tube through the oropharynx led to implantation of cells in the anterior
      abdominal wall. In these cases laparoscopic placement may be more beneficial to
      avoid this problem.

PMID- 16984649
TI  - U.S. and Canadian pharmacists' attitudes, knowledge, and professional practice
      behaviors toward dietary supplements: a systematic review.
AB  - BACKGROUND: Although dietary supplements (DS) are widely sold in pharmacies, the
      legal, ethical, and practice responsibilities of pharmacists with respect to
      these products have not been well defined. This systematic review of pharmacists'
      attitudes, knowledge, and professional practice behaviours toward DS is intended
      to inform pharmacy regulators' and educators' decision making around this topic.
      METHODS: Eligible studies were identified through a systematic database search
      for all available years through to March 2006. Articles were analyzed for this
      review if they included survey data on U.S. or Canadian pharmacists' attitudes,
      knowledge, or professional practice behaviors toward DS published in 1990 or
      later. RESULTS: Due to the heterogeneity of the data, it was not possible to draw
      a conclusion with respect to pharmacists' general attitudes toward DS.
      Approximately equal numbers of pharmacists report positive as well as negative
      attitudes about the safety and efficacy of DS. There is strong agreement among
      pharmacists for the need to have additional training on DS, increased regulation
      of DS, and quality information on DS. In addition, survey data indicate that
      pharmacists do not perceive their knowledge of DS to be adequate and that
      pharmacists do not routinely document, monitor, or inquire about patients' use of
      DS. Despite this, a large proportion of pharmacists reported receiving questions
      about DS from patients and other health care practitioners. CONCLUSION: Further
      research is needed to explore the factors that influence pharmacists' beliefs and
      attitudes about DS, to accurately evaluate pharmacists' knowledge of DS, and to
      uncover the reasons why pharmacists do not routinely document, monitor, or
      inquire about patients' use of DS.

PMID- 16984650
TI  - Validation of travel times to hospital estimated by GIS.
AB  - BACKGROUND: An increasing number of studies use GIS estimates of car travel times
      to health services, without presenting any evidence that the estimates are
      representative of real travel times. This investigation compared GIS estimates of
      travel times with the actual times reported by a sample of 475 cancer patients
      who had travelled by car to attend clinics at eight hospitals in the North of
      England. METHODS: Car travel times were estimated by GIS using the shortest road
      route between home address and hospital and average speed assumptions. These
      estimates were compared with reported journey times and straight line distances
      using graphical, correlation and regression techniques. RESULTS: There was a
      moderately strong association between reported times and estimated travel times
      (r = 0.856). Reported travel times were similarly related to straight line
      distances. Altogether, 50% of travel time estimates were within five minutes of
      the time reported by respondents, 77% were within ten minutes and 90% were within
      fifteen minutes. The distribution of over- and under-estimates was symmetrical,
      but estimated times tended to be longer than reported times with increasing
      distance from hospital. Almost all respondents rounded their travel time to the
      nearest five or ten minutes. The reason for many cases of reported journey times
      exceeding the estimated times was confirmed by respondents' comments as traffic
      congestion. CONCLUSION: GIS estimates of car travel times were moderately close
      approximations to reported times. GIS travel time estimates may be superior to
      reported travel times for modelling purposes because reported times contain
      errors and can reflect unusual circumstances. Comparison with reported times did
      not suggest that estimated times were a more sensitive measure than straight line
      distance.

PMID- 16984651
TI  - Human inflammatory bowel disease does not associate with Lawsonia intracellularis
      infection.
AB  - BACKGROUND: There is increasing evidence that bacterial infection of the
      intestinal mucosa may contribute to the pathogenesis of inflammatory bowel
      diseases (IBD). In pigs, an obligate intracellular bacterium, Lawsonia
      intracellularis (LI), was shown to cause proliferative enteropathy (PE) of which
      some forms display histological and clinical similarities to human IBD. Since LI
      similar Desulfovibrio spp. may infect human cells, we hypothesized that LI might
      be associated with the development of human IBD. RESULTS: In human intestinal
      tissue samples, PCR using LLG, 50SL27, LSA and strictly LI-specific 16SII
      primers, yielded either no amplicons or products with weak homology to human
      genomic sequences. Sequencing of these amplicons revealed no specificity for LI.
      However, amplification of DNA with less specific 16SI primers resulted in
      products bearing homology to certain Streptococcus species. These 16SI-amplified
      products were present in healthy and diseased specimens, without obvious
      prevalence. CONCLUSION: LI is not associated with the pathogenesis of UC or CD.
      Whether an immunologic response to commensal bacteria such as streptococci may
      contribute to the chronic inflammatory condition in IBD, remained to be
      determined.

PMID- 16984652
TI  - Genomes as geography: using GIS technology to build interactive genome feature
      maps.
AB  - BACKGROUND: Many commonly used genome browsers display sequence annotations and
      related attributes as horizontal data tracks that can be toggled on and off
      according to user preferences. Most genome browsers use only simple keyword
      searches and limit the display of detailed annotations to one chromosomal region
      of the genome at a time. We have employed concepts, methodologies, and tools that
      were developed for the display of geographic data to develop a Genome Spatial
      Information System (GenoSIS) for displaying genomes spatially, and interacting
      with genome annotations and related attribute data. In contrast to the paradigm
      of horizontally stacked data tracks used by most genome browsers, GenoSIS uses
      the concept of registered spatial layers composed of spatial objects for
      integrated display of diverse data. In addition to basic keyword searches,
      GenoSIS supports complex queries, including spatial queries, and dynamically
      generates genome maps. Our adaptation of the geographic information system (GIS)
      model in a genome context supports spatial representation of genome features at
      multiple scales with a versatile and expressive query capability beyond that
      supported by existing genome browsers. RESULTS: We implemented an interactive
      genome sequence feature map for the mouse genome in GenoSIS, an application that
      uses ArcGIS, a commercially available GIS software system. The genome features
      and their attributes are represented as spatial objects and data layers that can
      be toggled on and off according to user preferences or displayed selectively in
      response to user queries. GenoSIS supports the generation of custom genome maps
      in response to complex queries about genome features based on both their
      attributes and locations. Our example application of GenoSIS to the mouse genome
      demonstrates the powerful visualization and query capability of mature GIS
      technology applied in a novel domain. CONCLUSION: Mapping tools developed
      specifically for geographic data can be exploited to display, explore and
      interact with genome data. The approach we describe here is organism independent
      and is equally useful for linear and circular chromosomes. One of the unique
      capabilities of GenoSIS compared to existing genome browsers is the capacity to
      generate genome feature maps dynamically in response to complex attribute and
      spatial queries.

PMID- 16984653
TI  - Searching for interpretable rules for disease mutations: a simulated annealing
      bump hunting strategy.
AB  - BACKGROUND: Understanding how amino acid substitutions affect protein functions
      is critical for the study of proteins and their implications in diseases.
      Although methods have been developed for predicting potential effects of amino
      acid substitutions using sequence, three-dimensional structural, and evolutionary
      properties of proteins, the applications are limited by the complication of the
      features and the availability of protein structural information. Another
      limitation is that the prediction results are hard to be interpreted with
      physicochemical principles and biological knowledge. RESULTS: To overcome these
      limitations, we proposed a novel feature set using physicochemical properties of
      amino acids, evolutionary profiles of proteins, and protein sequence information.
      We applied the support vector machine and the random forest with the feature set
      to experimental amino acid substitutions occurring in the E. coli lac repressor
      and the bacteriophage T4 lysozyme, as well as to annotated amino acid
      substitutions occurring in a wide range of human proteins. The results showed
      that the proposed feature set was superior to the existing ones. To explore
      physicochemical principles behind amino acid substitutions, we designed a
      simulated annealing bump hunting strategy to automatically extract interpretable
      rules for amino acid substitutions. We applied the strategy to annotated human
      amino acid substitutions and successfully extracted several rules which were
      either consistent with current biological knowledge or providing new insights for
      the understanding of amino acid substitutions. When applied to unclassified data,
      these rules could cover a large portion of samples, and most of the covered
      samples showed good agreement with predictions made by either the support vector
      machine or the random forest. CONCLUSION: The prediction methods using the
      proposed feature set can achieve larger AUC (the area under the ROC curve),
      smaller BER (the balanced error rate), and larger MCC (the Matthews' correlation
      coefficient) than those using the published feature sets, suggesting that our
      feature set is superior to the existing ones. The rules extracted by the
      simulated annealing bump hunting strategy have comparable coverage and accuracy
      but much better interpretability as those extracted by the patient rule induction
      method (PRIM), revealing that the strategy is more effective in inducing
      interpretable rules.

PMID- 16984654
TI  - Zidovudine plus lamivudine in Human T-Lymphotropic Virus type-I-associated
      myelopathy: a randomised trial.
AB  - BACKGROUND: No therapies have been proven to persistently improve the outcome of
      HTLV-I-associated myelopathy. Clinical benefit has been reported with zidovudine
      and with lamivudine in observational studies. We therefore conducted a
      randomised, double blind, placebo controlled study of six months combination
      therapy with these nucleoside analogues in sixteen patients. RESULTS: Primary
      outcomes were change in HTLV-I proviral load in PBMCs and clinical measures.
      Secondary endpoints were changes in T-cell subsets and markers of activation and
      proliferation. Six patients discontinued zidovudine. No significant changes in
      pain, bladder function, disability score, gait, proviral load or markers of T
      cell activation or proliferation were seen between the two arms. Active therapy
      was associated with an unexplained decrease in CD8 and non-T lymphocyte counts.
      CONCLUSION: Failure to detect clinical improvement may have been due irreversible
      nerve damage in these patients with a long clinical history and future studies
      should target patients presenting earlier. The lack of virological effect but may
      reflect a lack of activity of these nucleoside analogues against HTLV-I RT in
      vivo, inadequate intracellular concentrations of the active moiety or the
      contribution of new cell infection to maintaining proviral load at this stage of
      infection may be relatively small masking the effects of RT inhibition.

PMID- 16984656
TI  - An unusual case of cardiac dysfunction after left ventricular reconstruction.
AB  - This report describes an unusual cause of low cardiac output after coronary
      artery bypass grafting and left ventricular remodeling. It details left
      ventricular remodeling techniques and discusses the most recent advances and
      outcomes. As well, significant attention is paid to the issues surrounding
      failure to separate from cardiopulmonary bypass.

PMID- 16984655
TI  - Consistency in electronic portal imaging registration in prostate cancer
      radiation treatment verification.
AB  - BACKGROUND: A protocol of electronic portal imaging (EPI) registration for the
      verification of radiation treatment fields has been implemented at our
      institution. A template is generated using the reference images, which is then
      registered with the EPI for treatment verification. This study examines
      interobserver consistency among trained radiation therapists in the registration
      and verification of external beam radiotherapy (EBRT) for patients with prostate
      cancer. MATERIALS AND METHODS: 20 consecutive patients with prostate cancer
      undergoing EBRT were analyzed. The EPIs from the initial 10 fractions were
      registered independently by 6 trained radiation therapist observers. For each
      fraction, an anterior-posterior (AP or PA) and left lateral (Lat) EPIs were
      generated and registered with the reference images. Two measures of displacement
      for the AP EPI in the superior-inferior (SI) and right left (RL) directions and
      two measures of displacement for the Lat EPI in the AP and SI directions were
      prospectively recorded. A total of 2400 images and 4800 measures were analyzed.
      Means and standard deviations, as well as systematic and random errors were
      calculated for each observer. Differences between observers were compared using
      the chi-square test. Variance components analysis was used to evaluate how much
      variance is attributed to the observers. Time trends were estimated using
      repeated measures analysis. RESULTS: Inter-observer variation expressed as the
      standard deviation of the six observers' measurements within each image were 0.7,
      1.0, 1.7 and 1.4 mm for APLR, APSI, LatAP and LatSI respectively. Variance
      components analysis showed that the variation attributed to the observers was
      small compared to variation due to the images. On repeated measure analysis, time
      trends were apparent only for the APLR and LatSI measurements. Their magnitude
      however was small. CONCLUSION: No clinically important systematic observer effect
      or time trends were identified in the registration of EPI by the radiation
      therapist observers in this study. These findings are useful in the documentation
      of consistency and reliability in the quality assurance of treatment verification
      of EBRT for prostate cancer.

PMID- 16984657
TI  - The impact of workplace risk factors on the occurrence of neck and upper limb
      pain: a general population study.
AB  - BACKGROUND: Work-related neck and upper limb pain has mainly been studied in
      specific occupational groups, and little is known about its impact in the general
      population. The objectives of this study were to estimate the prevalence and
      population impact of work-related neck and upper limb pain. METHODS: A cross
      sectional survey was conducted of 10,000 adults in North Staffordshire, UK, in
      which there is a common local manual industry. The primary outcome measure was
      presence or absence of neck and upper limb pain. Participants were asked to give
      details of up to five recent jobs, and to report exposure to six work activities
      involving the neck or upper limbs. Psychosocial measures included job control,
      demand and support. Odds ratios (ORs) and population attributable fractions were
      calculated for these risk factors. RESULTS: The age-standardized one-month period
      prevalence of neck and upper limb pain was 44%. There were significant
      independent associations between neck and upper limb pain and: repeated lifting
      of heavy objects (OR = 1.4); prolonged bending of neck (OR = 2.0); working with
      arms at/above shoulder height (OR = 1.3); little job control (OR = 1.6); and
      little supervisor support (OR = 1.3). The population attributable fractions were
      0.24 (24%) for exposure to work activities and 0.12 (12%) for exposure to
      psychosocial factors. CONCLUSION: Neck and upper limb pain is associated with
      both physical and psychosocial factors in the work environment. Inferences of
      cause-and-effect from cross-sectional studies must be made with caution;
      nonetheless, our findings suggest that modification of the work environment might
      prevent up to one in three of cases of neck and upper limb pain in the general
      population, depending on current exposures to occupational risk.

PMID- 16984658
TI  - Distributed data processing for public health surveillance.
AB  - BACKGROUND: Many systems for routine public health surveillance rely on
      centralized collection of potentially identifiable, individual, identifiable
      personal health information (PHI) records. Although individual, identifiable
      patient records are essential for conditions for which there is mandated
      reporting, such as tuberculosis or sexually transmitted diseases, they are not
      routinely required for effective syndromic surveillance. Public concern about the
      routine collection of large quantities of PHI to support non-traditional public
      health functions may make alternative surveillance methods that do not rely on
      centralized identifiable PHI databases increasingly desirable. METHODS: The
      National Bioterrorism Syndromic Surveillance Demonstration Program (NDP) is an
      example of one alternative model. All PHI in this system is initially processed
      within the secured infrastructure of the health care provider that collects and
      holds the data, using uniform software distributed and supported by the NDP. Only
      highly aggregated count data is transferred to the datacenter for statistical
      processing and display. RESULTS: Detailed, patient level information is readily
      available to the health care provider to elucidate signals observed in the
      aggregated data, or for ad hoc queries. We briefly describe the benefits and
      disadvantages associated with this distributed processing model for routine
      automated syndromic surveillance. CONCLUSION: For well-defined surveillance
      requirements, the model can be successfully deployed with very low risk of
      inadvertent disclosure of PHI--a feature that may make participation in
      surveillance systems more feasible for organizations and more appealing to the
      individuals whose PHI they hold. It is possible to design and implement
      distributed systems to support non-routine public health needs if required.

PMID- 16984659
TI  - Collision tumor of the thyroid: follicular variant of papillary carcinoma and
      squamous carcinoma.
AB  - BACKGROUND: Collision tumors of the thyroid gland are a rare entity. We present a
      case of a follicular variant of papillary carcinoma and squamous carcinoma in the
      thyroid. To the best of our knowledge, this is the first documentation of a
      collision tumor with a papillary carcinoma and a squamous carcinoma within the
      thyroid gland. The clinicopathological features and immunohistochemical profile
      are reported. The theories of origin, epidemiology and management are discussed
      with a literature review. CASE PRESENTATION: A 65 year old woman presented with a
      large thyroid swelling of 10 years duration and with swellings on the back and
      scalp which were diagnosed to be a follicular variant of papillary thyroid
      carcinoma with metastasis. Clinical examination, radiology and endoscopy ruled
      out any other abnormality of the upper aerodigestive tract. The patient was
      treated surgically with a total thyroidectomy with central compartment clearance
      and bilateral selective neck dissections. The histopathology revealed a collision
      tumor with components of both a follicular variant of papillary carcinoma and a
      squamous carcinoma. Immunohistochemical analysis confirmed the independent origin
      of these two primary tumors. Adjuvant radio iodine therapy directed toward the
      follicular derived component of the thyroid tumor and external beam radiotherapy
      for the squamous component was planned. CONCLUSION: Collision tumors of the
      thyroid gland pose a diagnostic as well as therapeutic challenge. Metastasis from
      distant organs and contiguous primary tumors should be excluded. The origins of
      squamous cancer in the thyroid gland must be established to support the true
      evolution of a collision tumor and to plan treatment. Treatment for collision
      tumors depends upon the combination of primary tumors involved and each component
      of the combination should be treated like an independent primary. The reporting
      of similar cases with longer follow-up will help define the epidemiology, biology
      and establish standardized protocols for treatment of these extremely rare
      tumors.

PMID- 16984660
TI  - Antidepressants and inflammatory bowel disease: a systematic review.
AB  - BACKGROUND: A number of studies have suggested a link between the patient's
      psyche and the course of inflammatory bowel disease (IBD). Although
      pharmacotherapy with antidepressants has not been widely explored, some
      investigators have proposed that treating psychological co-morbidities with
      antidepressants may help to control disease activity. To date a systematic
      analysis of the available studies assessing the efficacy of antidepressants for
      the control of somatic symptoms in IBD patients has not been performed. METHODS:
      We searched electronic databases, without any language restriction. All relevant
      papers issued after 1990 were examined. RESULTS: 12 relevant publications were
      identified. All of them referred to non-randomised studies. Antidepressants
      reported in these publications included paroxetine, bupropion, amitriptyline,
      phenelzine, and mirtazapine. In 10 articles, paroxetine, bupropion, and
      phenelzine were suggested to be effective for treating both psychological and
      somatic symptoms in patients suffering from IBD. Amitriptyline was found
      ineffective for treating somatic symptoms of IBD. Mirtazapine was not recommended
      for IBD patients. CONCLUSION: Although most of reviewed papers suggest a
      beneficial effect of treatment with antidepressants in patients with IBD, due to
      the lack of reliable data, it is impossible to judge the efficacy of
      antidepressants in IBD. Properly designed trials are justified and needed based
      upon the available uncontrolled data.

PMID- 16984661
TI  - Disease-modifying antirheumatic drugs are associated with a reduced risk for
      cardiovascular disease in patients with rheumatoid arthritis: a case control
      study.
AB  - Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk
      for cardiovascular disease (CVD). This study investigates possible associations
      between CVD and the use of conventional disease-modifying antirheumatic drugs
      (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient
      years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug
      treatment were evaluated from time of RA diagnosis up to the first cardiovascular
      event or the end of the follow-up period. The dataset was categorized according
      to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate
      (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA
      duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or
      MTX were used as a reference group. MTX treatment was associated with a
      significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to
      0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20
      (0.08 to 0.54). The risk reductions remained significant after additional
      correction for the presence of rheumatoid factor and erosions. After correction
      for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX,
      SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor
      positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07)
      and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were
      associated with significantly lower CVD risk compared to RA patients who never
      used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use,
      results in powerful suppression of inflammation, thereby reducing the development
      of atherosclerosis and subsequently clinically overt CVD.

PMID- 16984663
TI  - Digital image analysis for morphometric evaluation of tissue response after
      implanting alloplastic vascular prostheses.
AB  - The aim of this study was to examine the suitability of digital image analysis,
      using the KS400 software system, for the morphometric evaluation of the tissue
      response after prosthesis implantation in an animal model. Twenty-four female
      pigs aged 10 weeks were implanted with infrarenal Dacron(R) prostheses for 14,
      21, 28, and 116 days. Following the explantation and investigation of the
      neointima region, the expression of beta-1-integrin, the proliferation rate by
      means of Ki-67 positive cells, and the intima thickness were evaluated as
      exemplary parameters of the tissue response after implantation. Frozen tissue
      sections were immunohistochemically stained and subsequently examined using
      computer-aided image analysis. A maximum expression of 32.9% was observed for
      beta-1-integrin 14 days after implantation, gradually declining over time to 9.8%
      after 116 days. The proliferation rate was found to be 19% on day 14, increasing
      to 39% on day 21 with a subsequent gradual decline to 5% after 116 days. The
      intima thickness increased from 189.9 microm on day 14 to 1228.0 microm on day
      116. In conclusion, digital image analysis was found to be an efficient and
      reproducible method for the morphometric evaluation of a peri-prosthetic tissue
      response.

PMID- 16984664
TI  - Design of cerebellar and nontegmental rhombencephalic microvascular bed in the
      sterlet, Acipenser ruthenus: a scanning electron microscope and 3D morphometry
      study of vascular corrosion casts.
AB  - The design of the microvasculature of cerebellum and nontegmental rhombencephalic
      areas was studied in eight adult Acipenser ruthenus L. by scanning electron
      microscopy of vascular corrosion casts and three-dimensional morphometry. Gross
      vascularization was described and diameters and total branching angles of parent
      and daughter vessels of randomly selected arterial and capillary bifurcations
      (respectively, venous mergings) were measured. With diameters ranging from 15.9
      +/- 1.9 microm (cerebellum; mean +/- S.D.) to 15.9 +/- 1.7 mm (nontegmental
      rhombencephalon; mean +/- S.D.) capillaries in Acipenser were significantly (p >
      or = .05) smaller than in cyclostomes (18-20 microm) but significantly thicker
      than in higher vertebrates and men (6-8 microm). With the exception of the area
      ratio beta (i.e., sum of squared daugther diameters divided by squared diameter
      of parent vessel) of the venular mergings in the nontegmental rhombencephalon, no
      significant differences (p > or = .05) existed between the two brain areas. Data
      showed that arteriolar and capillary bifurcations and venular mergings are
      optimally designed in respect to diameters of parent vessel to daughter vessels
      and to branching (merging) angles. Quantitative data are discussed both in
      respect to methodical pitfalls and the optimality principles possibly underlying
      the design of vascular bifurcations/mergings in selected brain areas of a
      nonteleost primitive actinopterygian fish.

PMID- 16984665
TI  - Epicardial development in the rat: a new perspective.
AB  - Development of the epicardium is critical to proper heart formation. It provides
      all of the precursor cells that form the coronary system and supplies signals
      that stimulate cardiac myocyte proliferation. The epicardium forms from
      mesothelial cells associated with the septum transversum and is referred to as
      the proepicardium (PE). Two different methods by which these PE cells colonize
      the developing heart have been described. In avians, PE cells form a bridge to
      the heart over which PE cells migrate onto the heart. In fish and mammals, PE
      cells form vesicles of cells that detach from the mesothelium, float through the
      pericardial cavity, and attach to the heart. A previous study of rat PE
      development investigated this process at the histological level. Protein markers
      have been developed since this study. Thus, we investigated this important
      developmental process coupled with these new markers using other visualization
      techniques such as scanning electron microscopy (SEM) and confocal microscopy.
      Finally, a novel, three-dimensional (3-D) culture system was used to confirm the
      identity of the PE cells. In this study, we found convincing evidence that the
      rat PE cells directly attach to the heart in a manner similar to that observed in
      avians.

PMID- 16984666
TI  - Phagocytosis of PLGA microparticles in rat peritoneal exudate cells: a time
      dependent study.
AB  - With the purpose of enhancing the efficacy of microparticle-encapsulated
      therapeutic agents, in this study we evaluated the phagocytic ability of rat
      peritoneal exudate cells and the preferential location of poly(d,l-lactide-co
      glycolic acid) (PLGA) microparticles inside these cells. The microparticles used
      were produced by a solvent evaporation method and were characterized by dynamic
      light scattering (DLS), transmission electron microscopy (TEM), and scanning
      electron microscopy (SEM). Size distribution analysis using DLS and SEM showed
      that the particles were spherical, with diameters falling between 0.5 and 1.5
      mum. Results from cell adhesion by SEM assay, indicated that the PLGA
      microparticles are not toxic to cells and do not cause any distinct damage to
      them as confirmed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide) assay. Among the large variety of cell populations found in
      the peritoneal exudates (neutrophils, eosinophils, monocytes, and macrophages),
      TEM showed that only the latter phagocytosed PLGA microparticles, in a time
      dependent manner. The results obtained indicate that the microparticles studied
      show merits as possible carriers of drugs for intracellular delivery.

PMID- 16984667
TI  - The determination of the efficiency of energy dispersive X-ray spectrometers by a
      new reference material.
AB  - A calibration procedure for the detection efficiency of energy dispersive X-ray
      spectrometers (EDS) used in combination with scanning electron microscopy (SEM)
      for standardless electron probe microanalysis (EPMA) is presented. The procedure
      is based on the comparison of X-ray spectra from a reference material (RM)
      measured with the EDS to be calibrated and a reference EDS. The RM is certified
      by the line intensities in the X-ray spectrum recorded with a reference EDS and
      by its composition. The calibration of the reference EDS is performed using
      synchrotron radiation at the radiometry laboratory of the Physikalisch-Technische
      Bundesanstalt. Measurement of RM spectra and comparison of the specified line
      intensities enables a rapid efficiency calibration on most SEMs. The article
      reports on studies to prepare such a RM and on EDS calibration and proposes a
      methodology that could be implemented in current spectrometer software to enable
      the calibration with a minimum of operator assistance.

PMID- 16984668
TI  - EELS investigations of different niobium oxide phases.
AB  - Electron energy loss spectra in conjunction with near-edge fine structures of
      purely stoichiometric niobium monoxide (NbO) and niobium pentoxide (Nb2O5)
      reference materials were recorded. The structures of the niobium oxide reference
      materials were checked by selected area electron diffraction to ensure a proper
      assignment of the fine structures. NbO and Nb2O5 show clearly different energy
      loss near-edge fine structures of the Nb-M4,5 and -M2,3 edges and of the O-K
      edge, reflecting the specific local environments of the ionized atoms. To
      distinguish the two oxides in a quantitative manner, the intensities under the Nb
      M4,5 as well as Nb-M2,3 edges and the O-K edge were measured and their ratios
      calculated. k-factors were also derived from these measurements.

PMID- 16984669
TI  - Spatially resolved energy electron loss spectroscopy studies of iron oxide
      nanoparticles.
AB  - The oxidation state of iron oxide nanoparticles co-generated with soot during a
      combustion process was studied using electron energy-loss spectroscopy (EELS).
      Spatially resolved EELS spectra in the scanning transmission electron microscopy
      mode were collected to detect changes in the oxidation state between the cores
      and surfaces of the particles. Quantification of the intensity ratio of the white
      lines of the iron L-ionization edge was used to measure the iron oxidation state.
      Quantitative results obtained from Pearson's method, which can be directly
      compared with the literature data, indicated that the L3 /L2-intensity ratio for
      these particles changes from 5.5 +/- 0.3 in the particles' cores to 4.4 +/- 0.3
      at their surfaces. This change can be directly related to the reduction of the
      iron oxidation state at the surface of the particles. Experimental results
      indicate that the cores of the particles are composed of gamma-Fe2O3, which seems
      to be reduced to FeO at their surfaces. These results were also supported by the
      fine structure of the oxygen K-edge and by the significant chemical shift of the
      iron L-edge.

PMID- 16984670
TI  - Quantification problems in depth profiling of pwr steels using Ar+ ion sputtering
      and XPS analysis.
AB  - The oxide scales of AISI 304 formed in boric acid solutions at 300 degrees C and
      pH = 4.5 have been studied using X-ray photoelectron spectroscopy (XPS) depth
      profiling. The present focus is depth profile quantification both in depth and
      chemical composition on a molecular level. The roughness of the samples is
      studied by atomic force microscopy before and after sputtering, and the erosion
      rate is determined by measuring the crater depth with a surface profilometer and
      vertical scanning interferometry. The resulting roughness (20-30 nm), being an
      order of magnitude lower than the crater depth (0.2-0.5 microm), allows layer-by
      layer profiling, although the ion-induced effects result in an uncertainty of the
      depth calibration of a factor of 2. The XPS spectrum deconvolution and data
      evaluation applying target factor analysis allows chemical speciation on a
      molecular level. The elemental distribution as a function of the sputtering time
      is obtained, and the formation of two layers is observed-one hydroxide (mainly
      iron-nickel based) on top and a second one deeper, mainly consisting of iron
      chromium oxides.

PMID- 16984672
TI  - Balancing evidence and public opinion in health technology assessments: the case
      of leukoreduction.
AB  - Leukoreduction, filtering white blood cells from transfusion blood, effectively
      avoids leukocyte-related complications of blood transfusion. The technology has
      proven its relative cost-effectiveness for specific patient populations. With the
      advent of variant Creutzfeldt-Jakob disease, a transmittable spongiform
      encephalopathy caused by mad cow disease (bovine spongiform encephalopathy), the
      hard hit United Kingdom introduced universal leukoreduction for all patients as a
      precaution for transmission of prions in 1999. This costly policy was followed by
      many other countries, in the absence of much evidence of an actual health problem
      or of a more than presumed effectiveness of leukoreduction in preventing prion
      transmission. The core problem proved to be legal. The blood banks are legally
      accountable for blood safety. This accountability is absolute, based on avoidance
      of all possible risks, regardless of costs. This strategy leads to inefficiencies
      in health care: (i) blood safety management is guided by available rather than
      cost-effective technology, and (ii) private insurance premiums for civil
      liability are sharply increasing, while they are in no way related to the
      expected returns and the high and increasing blood safety. A rational safety
      policy is to be optimal, taking into account costs and effects of the safety
      procedures. This issue will need an open discussion with the general public of
      the real risks and a clear and unambiguous definition of proportionality in the
      precautionary principle, based on the European law.

PMID- 16984673
TI  - Need for high-quality studies in health technology assessments: the case of a
      systematic review of treatment for retinoblastoma.
AB  - OBJECTIVES: The aim of this study was to conduct a systematic review of the
      evidence for treatments for retinoblastoma in children. METHODS: Seventeen
      electronic databases were searched. Two reviewers independently selected studies.
      Studies of participants diagnosed with childhood retinoblastoma, any
      interventions, and all clinical outcomes were eligible. Randomized and
      nonrandomized controlled trials and cohort studies with clear comparisons between
      treatment groups were included. Methodological quality was assessed. RESULTS:
      Thirty-one observational comparative studies were included, of which twenty-seven
      were retrospective. The methodological quality was generally poor, with a high
      risk of selection bias in all studies. Although there were high levels of
      treatment success in many of the studies, due to the limitations of the evidence
      identified, it was not possible to make meaningful and robust conclusions about
      the relative effectiveness of different treatment approaches for retinoblastoma
      in children. CONCLUSIONS: Good quality randomized controlled trials are required.
      Where controlled trials are not feasible, only high quality prospective,
      nonrandomized studies should be given consideration, due to the generally higher
      risk of bias in retrospective studies.

PMID- 16984674
TI  - International diffusion of new health technologies: a ten-country analysis of six
      health technologies.
AB  - OBJECTIVES: The objective of this study was to examine and explain the
      differential international diffusion of six health innovations. METHODS: A
      retrospective diffusion study was undertaken of sildenafil, cyclooxygenase-II
      (COX II) inhibitors, beta interferon, verteporfin, deep brain stimulators, and
      drug-eluting coronary stents in ten countries-Australia, Canada, Denmark, France,
      The Netherlands, Norway, Spain, Sweden, Switzerland, and the United Kingdom. We
      plotted diffusion curves of daily defined doses per quarter, vials or implants
      per million population, and examined the association between diffusion and five
      key variables. RESULTS: Canada, Switzerland, and Sweden are generally high users
      of new technologies; Spain, Denmark, and particularly the United Kingdom are low
      users. Almost all countries experienced rapid adoption of sildenafil with
      diffusion to a similar level; there was variable adoption and diffusion of COX II
      inhibitors, verteporfin, and interferon beta; drug-eluting stents penetrated the
      market in a similar way in all but one country; and two countries had very
      different adoption patterns for deep brain stimulators. Above average health
      spending and the presence of health technology assessment (HTA) or other guidance
      reports are consistently associated with increased diffusion. Early warning
      activity and a national coverage decision being taken are more likely to be
      associated with a reduced diffusion. CONCLUSIONS: The significant differences in
      diffusion between different countries are not consistent with a neat evidence
      based world. The tools available to policy makers to control diffusion (early
      warning systems, HTA, and a fourth hurdle) play some part in influencing
      diffusion but need close scrutiny of how successfully they operate.

PMID- 16984675
TI  - Managing external risks to health technology assessment programs.
AB  - OBJECTIVES: The aim of this study was to develop a guide to identifying and
      managing risks for health technology assessment (HTA) programs and to obtain
      opinions on this topic from HTA agencies. METHODS: The risks and approaches to
      their management were compiled, drawing on experiences from HTA programs and the
      risk assessment literature. Opinion on this classification was obtained from
      members of the International Network of Agencies for Health Technology Assessment
      (INAHTA). RESULTS: Twenty-one risks for HTA programs were identified under the
      categories Formulation of HTA Questions, Preparation of the HTA Product,
      Dissemination, and Contracting. For each risk area, potential consequences and
      suggested management approaches were outlined. Responses from ten HTA programs
      indicated substantial agreement regarding the risks that had been identified and
      on the importance of risk management for their own operations. CONCLUSIONS:
      Prudent management of HTA programs should take into account the risks related to
      external factors.

PMID- 16984676
TI  - Cost-effectiveness of self-management in asthma: a systematic review of peak flow
      monitoring interventions.
AB  - OBJECTIVES: It is generally accepted that home peak flow monitoring increases
      patients' self-management and could lead to cost savings. The aim of this review
      was to analyze costs and the cost-effectiveness of self-management based on peak
      flow monitoring interventions in asthma. METHODS: Twenty-one studies were
      included in this review. Data were extracted, and methodological and economic
      quality were assessed. These studies presented economic information regarding
      self-management interventions based on peak flow monitoring in asthmatics. The
      mean methodological quality was 4.6 (maximum 8), and the mean economic quality
      was 12.0 (maximum 15). RESULTS: In eighteen studies, the interventions led to net
      savings compared with usual care or less intensive intervention. Only three
      studies found the total costs to be higher in the intervention group. In thirteen
      of the seventeen studies that analyzed health outcomes, at least one of the
      reported health outcomes improved statistically significantly after the
      intervention. However, the methods of economic evaluation differed among the
      studies and were not always in line with the standard methodology. CONCLUSIONS:
      The interventions, costs, and outcomes were very diverse. The results emphasize
      the need for guidelines to increase the comparability of cost-effectiveness
      evaluations relating to asthma. Only then will it be possible to conclude whether
      interventions for asthmatics, such as self-management based on peak flow
      monitoring interventions, are cost-effective.

PMID- 16984677
TI  - Cost-effectiveness of a preventive counseling and support package for postnatal
      depression.
AB  - OBJECTIVES: This study reports the cost-effectiveness of a preventive
      intervention, consisting of counseling and specific support for the mother-infant
      relationship, targeted at women at high risk of developing postnatal depression.
      METHODS: A prospective economic evaluation was conducted alongside a pragmatic
      randomized controlled trial in which women considered at high risk of developing
      postnatal depression were allocated randomly to the preventive intervention (n =
      74) or to routine primary care (n = 77). The primary outcome measure was the
      duration of postnatal depression experienced during the first 18 months
      postpartum. Data on health and social care use by women and their infants up to
      18 months postpartum were collected, using a combination of prospective diaries
      and face-to-face interviews, and then were combined with unit costs ( pound, year
      2000 prices) to obtain a net cost per mother-infant dyad. The nonparametric
      bootstrap method was used to present cost-effectiveness acceptability curves and
      net benefit statistics at alternative willingness to pay thresholds held by
      decision makers for preventing 1 month of postnatal depression. RESULTS: Women in
      the preventive intervention group were depressed for an average of 2.21 months
      (9.57 weeks) during the study period, whereas women in the routine primary care
      group were depressed for an average of 2.70 months (11.71 weeks). The mean health
      and social care costs were estimated at pounds sterling 2,396.9 per mother-infant
      dyad in the preventive intervention group and pounds sterling 2,277.5 per mother
      infant dyad in the routine primary care group, providing a mean cost difference
      of pounds sterling 119.5 (bootstrap 95 percent confidence interval [CI], -535.4,
      784.9). At a willingness to pay threshold of pounds sterling 1,000 per month of
      postnatal depression avoided, the probability that the preventive intervention is
      cost-effective is .71 and the mean net benefit is pounds sterling 383.4
      (bootstrap 95 percent CI, - pounds sterling 863.3- pounds sterling 1,581.5).
      CONCLUSIONS: The preventive intervention is likely to be cost-effective even at
      relatively low willingness to pay thresholds for preventing 1 month of postnatal
      depression during the first 18 months postpartum. Given the negative impact of
      postnatal depression on later child development, further research is required
      that investigates the longer-term cost-effectiveness of the preventive
      intervention in high risk women.

PMID- 16984678
TI  - Cost-effectiveness of implementing national guidelines in the treatment of acute
      otitis media in children.
AB  - OBJECTIVES: Acute otitis media (AOM) is one of the most common diseases of
      childhood, representing a major disease burden on the society. New evidence-based
      guidelines for AOM, focusing on children under 7 years of age, were introduced in
      Finland in 1999. The aim of this study was to evaluate the cost-effectiveness of
      implementing those guidelines in Finland. METHODS: A 5-year prospective trial was
      conducted in thirty community primary healthcare centers in Finland. All AOM
      patients between 0 and 6 years of age visiting the study health centers for the
      first time, for this episode of illness, during 1 week in November 1998 (n = 579)
      and November 2002 (n = 369) were included in this study. The outcome measure was
      the percentage of symptom-free patients. RESULTS: The mean direct cost of an AOM
      episode per patient stayed almost the same after implementing the guidelines,
      euro152 in 1998 and euro150 in 2002. After implementing the guidelines, the
      percentage of symptom-free patients was 10 percentage points higher than before
      the guidelines. The treatment after the implementation of the guidelines, thus,
      was a dominant strategy. CONCLUSIONS: Implementing the guidelines to the
      treatment of AOM in children was associated with extra health benefits at
      slightly lower direct costs and, thus, is a dominant strategy. The focus of this
      study was on the short-term effects of the treatment; including long-term effects
      in the analysis might affect the results.

PMID- 16984679
TI  - Methodological approach for assessing the cost-effectiveness of treatments using
      longitudinal observational data: the SOHO study.
AB  - OBJECTIVES: The objective of this study was to develop a method to allocate
      treatment effects when patients switch medication frequently in longitudinal
      observational studies and apply the approach to assess the cost-effectiveness of
      treatments in the Schizophrenia Outpatient Health Outcomes (SOHO) study. METHODS:
      Data were collected on patients at entry to the SOHO study at 3, 6, and 12
      months. The 12-month follow-up period was considered as three epochs: 0-3 months,
      3-6 months, and 6-12 months. Patients who switched treatment at 3 months had
      their new treatment considered as a new baseline observation, as these two 3
      month observations provide two sets of information on the cost-effectiveness of a
      drug in the first 3 months after initiation. Multivariate regression analysis was
      used to adjust for baseline covariates. The model allowed for flexible functional
      forms, and the cost data were modeled using an exponential mean function.
      Bootstrapping assessed the uncertainty of the estimated parameters and
      incremental cost-effectiveness analysis decision rule. RESULTS AND CONCLUSIONS:
      We show the feasibility of the epoch analysis approach using data from the SOHO
      study comparing two antipsychotics. Estimates for the incremental cost and
      effectiveness per epoch over the full 12-month period are presented. Using the
      estimates of 200 bootstrap samples, we demonstrate how one drug is cost-effective
      compared with another.

PMID- 16984680
TI  - Model to assess the cost-effectiveness of new treatments for depression.
AB  - OBJECTIVES: The objective of this study was to develop a model to assess the cost
      effectiveness of a new treatment for patients with depression. METHODS: A Markov
      simulation model was constructed to evaluate standard care for depression as
      performed in clinical practice compared with a new treatment for depression.
      Costs and effects were estimated for time horizons of 6 months to 5 years. A
      naturalistic longitudinal observational study provided data on costs, quality of
      life, and transition probabilities. Data on long-term consequences of depression
      and mortality risks were collected from the literature. Cost-effectiveness was
      quantified as quality-adjusted life-years (QALYs) gained from the new treatment
      compared with standard care, and the societal perspective was taken.
      Probabilistic analyses were conducted to present the uncertainty in the results,
      and sensitivity analyses were conducted on key parameters used in the model.
      RESULTS: Compared with standard care, the new hypothetical therapy was predicted
      to substantially decrease costs and was also associated with gains in QALYs. With
      an improved treatment effect of 50 percent on achieving full remission, the net
      cost savings were 20,000 Swedish kronor over a 5-year follow-up time, given equal
      costs of treatments. Patients gained .073 QALYs over 5 years. The results are
      sensitive to changes in assigned treatment effects. CONCLUSIONS: The present
      study provides a new model for assessing the cost-effectiveness of treatments for
      depression by incorporating full remission as the treatment goal and QALYs as the
      primary outcome measure. Moreover, we show the usefulness of naturalistic real
      life data on costs and quality of life and transition probabilities when modeling
      the disease over time.

PMID- 16984681
TI  - Comprehensive cardiac rehabilitation: a cost assessment based on a randomized
      clinical trial.
AB  - OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and
      compared to the corresponding costs of usual care. The effect on health-related
      quality of life is analyzed. METHODS: An unprecedented and very detailed cost
      assessment was carried out, as no guidelines existed for the situation at hand.
      Due to challenging circumstances, the cost assessment turned out to be ex-post
      and top-down. RESULTS: Cost per treatment sequence is estimated to be
      approximately euro 976, whereas the incremental cost (compared with usual care)
      is approximately euro 682. The cost estimate is uncertain and may be as high as
      euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than
      usual care, and the higher costs are not outweighed by a quality of life gain.
      Comprehensive cardiac rehabilitation is, therefore, not cost-effective.

PMID- 16984682
TI  - Reanalysis of systematic reviews: the case of invasive strategies for acute
      coronary syndromes.
AB  - OBJECTIVES: The objective of this study was to collect all systematic reviews on
      invasive strategies for acute coronary syndromes (ACS) and reanalyze the data in
      these reviews to reach combined estimates, as well as to make predictions on the
      effectiveness and risk of harm so as to facilitate relevant decision making in
      health care. METHODS: The data sources used were the following electronic
      databases, searched from 1994 to September 2004: Cochrane Database of Systematic
      Reviews; Cochrane Central Register of Controlled Trials; DARE, HTA, EED (NHS
      CRD); MEDLINE In-Process, Other Non-Indexed Citations, MEDLINE, and PubMed (2000
      to 2004). References to the identified systematic reviews were checked. An
      ancillary search to identify recent randomized controlled trials (RCTs) covering
      the period from January 2003 to January 2006 was done in MEDLINE(R). We included
      systematic reviews of RCTs on patients with ACS. In unstable angina and non-ST
      elevation myocardial infarction (UA/NSTEMI), eligible reviews had to compare
      early routine invasive strategy with early selective invasive strategy. In ST
      elevation myocardial infarction (STEMI), a comparison between primary
      percutaneous coronary intervention (PCI) and thrombolytic therapy was required.
      The methodological quality of the reviews was assessed, and a standardized data
      extraction form was used. Results for the main outcomes of the RCTs in the
      reviews were reanalyzed. An additional search of those RCTs not included in the
      meta-analyses was performed for UA/NSTEMI and short-term morality data on STEMI.
      Bayesian models were constructed to estimate the uncertainty about a possible
      treatment effect and to make predictions and probability statements. Main results
      are based on these analyses. Mortality was considered as the primary outcome
      measure. RESULTS: One systematic review on invasive strategies was identified for
      UA/NSTEMI and nine on invasive strategies for STEMI. Five reviews of the latter
      that were published after the year 2000 were included for the final analysis. The
      median quality score was 10.5 (range, 7-13; n = 6) on a scale from 0 to 18
      points. An updated literature search identified one further RCT on UA/NSTEMI.
      Regarding NSTEMI and mortality, the average risk difference favoring an early
      invasive treatment strategy compared with early conservative strategy was .6
      percent (95 percent credible interval [CrI], -2.1 to 1.0). Predicted risk
      (relative risk/risk difference scales) of doing harm was 26.7/26.6 percent.
      Regarding STEMI and mortality, the absolute risk reduction in favor of primary
      PCI over thrombolysis was 4.1 percent (95 percent CrI, -7.1 to -1.1) when PCI was
      compared with streptokinase and 1.2 percent (95 percent CrI, -2.7 to .2) when
      compared with fibrin-specific thrombolytics. Predicted risk of harm was 8.9/5.3
      percent and 8.0/13.3 percent, respectively. CONCLUSIONS: There seems to be at
      present no solid evidence for survival benefit on early invasive strategy for
      UA/NSTEMI as a broad diagnostic group, and the risk of doing harm should be
      considered. Also, the evidence for PCI to decrease early mortality after STEMI is
      scanty. Estimations of predicted harm may further aid decisions on whether to
      implement the new treatment over the old one. It may also give an additional
      dimension for interpreting the results of any meta-analysis.

PMID- 16984683
TI  - Survey on the involvement of consumers in health technology assessment programs.
AB  - OBJECTIVES: The aim of this study was to obtain information from members of the
      International Network of Agencies for Health Technology Assessment (INAHTA) on
      their involvement of consumers (patients, carers, and related organizations) in
      their programs. METHODS: A questionnaire for a survey was developed and sent to
      member agencies in October 2005. RESULTS: Of the thirty-seven agencies that
      provided responses, 57 percent involve consumers in some aspects of their HTA
      programs and 83 percent intend to involve consumers in the future. Summaries of
      HTA reports that are intended to be easily understood by consumers are prepared
      by 49 percent of the agencies, and 36 percent involve consumers in dissemination
      of HTA material. CONCLUSIONS: Most INAHTA members involve consumers in some
      aspects of their programs, although not always routinely. Involvement seems
      likely to increase in the future.

PMID- 16984684
TI  - Disseminating evidence from health technology assessment: the case of tobacco
      prevention.
AB  - OBJECTIVES: The aims of the present study were to investigate the awareness among
      dentists and dental hygienists of evidence-based reports and guidelines on
      tobacco cessation activities and the impact these publications had on clinical
      practice. METHODS: A questionnaire was mailed to dental hygienists and dentists
      in Stockholm County, Sweden, and the results were compared with a previous
      investigation. RESULTS: Among the respondents, awareness of a popular science
      version of a systematic review on smoking and its effect on oral health was
      reported by 90 percent of the hygienists and 66 percent of the dentists. The
      information was used in clinical work by 34 percent of the dentists and 54
      percent of the hygienists. Reported changes in patterns of practice were more
      frequent recommendations to use nicotine replacement therapy and a more
      widespread use of setting quit dates. Approximately one quarter of the dental
      professionals reported that they had increased tobacco cessation consultation
      because of the results from the reports. CONCLUSIONS: Changes in patterns of
      practice were observed after dissemination of evidence-based information on
      tobacco cessation. Methods that were proven to be effective in the evidence-based
      report such as discussing quit dates and recommending nicotine replacement
      therapy were more commonly used after the publication of the report. Short,
      popular versions of extensive systematic reviews seem to be useful for
      implementing evidence-based knowledge and changing clinical practice.

PMID- 16984686
TI  - Health economic evaluations: how to find them.
AB  - OBJECTIVES: The aim of this study was to demonstrate the best way of identifying
      all relevant published health economic evaluation studies, which have increased
      in number rapidly in the past few decades. Nevertheless, health technology
      assessment projects are often faced with a scarcity of relevant studies. METHODS:
      Six bibliographic databases were searched using various individually adapted
      strategies. The particular example involves the cost-effectiveness of diagnosing
      gastroesophageal reflux disease. Inclusion and exclusion criteria were
      formulated. RESULTS: After irrelevant studies and duplicates had been excluded,
      sixty-eight abstracts were reviewed. We chose forty-one of them as relevant for
      full-text review, which identified fourteen papers as having met the inclusion
      criteria. Most of the relevant studies were identified by searching the National
      Health Service Economic Evaluation Database (NHS EED) and PubMed databases.
      CONCLUSIONS: A search in NHS EED, by means of the Cochrane Library or the Center
      for Reviews and Dissimination, along with a supplementary search in PubMed, is
      generally an appropriate, cost-effective strategy. However, because "cost
      effectiveness" is not consistently indexed with Medical Subject Heading terms in
      PubMed, all economic search terms need to be used to fully identify the relevant
      references.

PMID- 16984687
TI  - Future costs of stroke in the Netherlands: the impact of stroke services.
AB  - OBJECTIVES: In the next decades, the number of stroke patients is expected to
      increase. Furthermore, organizational changes, such as stroke services, are
      expected to be implemented on a large scale. The purpose of this study is to
      estimate the future healthcare costs by taking into account the expected increase
      of stroke patients and a nationwide implementation of stroke services. METHODS:
      By means of a dynamic multistate life table, the total number of stroke patients
      can be projected. The model calculates the annual number of patients by age and
      gender. The total healthcare costs are calculated by multiplying the average
      healthcare costs specified by age, gender, and healthcare sector with the total
      number of stroke patients specified by age and gender. RESULTS: In the year 2000,
      the healthcare costs for stroke amounted to euro 1.62 billion. This amount is
      approximately 4.4 percent of the total national healthcare budget. Projections of
      the total costs of stroke based on current practice result in an increase of 28
      percent (euro 2.08 billion) in the year 2020. A nationwide implementation of
      stroke services in 2020 would result in a substantial reduction of the costs of
      stroke (euro 1.81 billion: 13 percent cost reduction) compared with the regular
      care scenario. CONCLUSIONS: A nationwide implementation of stroke services is a
      strong policy tool for cost containment of health care in an aging population
      like that in the Netherlands. Policy makers should optimize the organization of
      stroke care.

PMID- 16984688
TI  - Cost of home and hospital care for patients with cystic fibrosis followed up in
      two reference medical centers in France.
AB  - OBJECTIVES: In France, new guidelines for clinical practices concerning cystic
      fibrosis came out in 2002, underscoring the need for early and intensive
      management of this disease. Because no recent health economic studies on cystic
      fibrosis in France were available, we conducted a cost-analysis study before the
      new guidelines were put into practice, with a view to a later study on the
      medical and economic impact of these guidelines. METHODS: A cost-analysis study
      was performed of the inpatient and outpatient costs of patients with cystic
      fibrosis for the 2000-2001 period. The various direct costs were estimated on a
      sample of sixty-five adult and pediatric patients managed for cystic fibrosis in
      two reference medical centers. Data were obtained from medical records, and
      questionnaires were filled out by the patients. Analysis was made from the
      perspective of the French healthcare system. RESULTS: We studied sixty-five
      patients, 54 percent male patients and 72 percent children under 18 years of age.
      The total cost of cystic fibrosis care totaled 16,189 euros per year and per
      patient. Outpatient costs accounted for 88 percent of the total cost versus 12
      percent for inpatient costs; medication costs were the highest with 21 percent of
      the total cost for home intravenous antibiotic treatments and 49 percent of the
      total cost for chronic medications. CONCLUSIONS: The results show that outpatient
      costs were higher than inpatient costs, which could be related to the importance
      granted to home health care in France, notably for intravenous antibiotic
      treatments given for pulmonary complications.

PMID- 16984689
TI  - Trends in diagnostic imaging utilization in a university hospital in Turkey.
AB  - OBJECTIVES: The aim of this study was to evaluate utilization trends of the
      diagnostic imaging examinations during the past decade in a university hospital
      in Turkey. METHODS: Patient registries of a university hospital were used for the
      years 1995 and 2003. The data set consisted of patients' admissions, social
      security status, and diagnostic imaging tests. RESULTS: When compared with 1995
      data, the total number of diagnostic imaging examinations and patient admissions
      increased 65.9 percent and 81.6 percent, respectively, in the year 2003. Although
      the total number of diagnostic imaging tests decreased 9.0 percent, there was a
      145.4 percent increase in magnetic resonance imaging (MRI) examinations.
      Nevertheless, radiological diagnostic procedures consisted of 12.8 percent of the
      total hospital revenues in 1995 and 9.4 percent in 2003. CONCLUSIONS: This study
      shows that approximately one third of inpatients underwent MRI and computed
      tomography examinations in 2003. The utilization rates of diagnostic imaging
      procedures, especially new technologies, need to be considered carefully with
      respect to appropriateness of procedures and planning of services.

PMID- 16984690
TI  - Analysis of the pharmaceuticals market and its technological development in
      Turkey.
AB  - OBJECTIVES: The objectives of this study were to analyze the current structure of
      the Turkish pharmaceuticals market to explain the latest developments and to
      offer some insight into the likely policy issues that this sector will face.
      METHODS: Systematic searches of the relevant Turkish and English research
      literature were made, using electronic databases in addition to written reports.
      RESULTS: The pharmaceutical industry in Turkey currently has eighty-seven
      manufacturing firms, eleven raw material manufacturers and thirty-eight importing
      firms. These add up to a total of 136 firms, 35 of which are driven by foreign
      capital, with 8 of these foreign-run firms having their own plants in Turkey. The
      industry employs approximately 19,000 personnel. In terms of growth, the value of
      pharmaceutical products in Turkey recently has exceeded that in Europe. In
      addition, per capita drug consumption levels are quite low compared with the
      Organisation for Economic Co-operation and Development and European Union
      countries. Major international players in the medical equipment and
      pharmaceutical products sector have also been opening offices in Turkey to reap
      the benefits of this rapidly evolving market. CONCLUSIONS: The pharmaceutical
      industry in Turkey is quite advanced and diverse, with high quality, generic
      pharmaceutical products being manufactured as well as poor quality copies that
      have not been appropriately tested in terms of bioequivalence and
      bioavailability. The country faces a low level of drug consumption due to
      economic and cultural constraints compared with Western countries. Governmental
      control and regulations are key issues because the majority of drug purchases (70
      80 percent) throughout the country are currently reimbursable through public
      sector agencies such as the Pension Fund and the Social Insurance Organization.

PMID- 16984691
TI  - ErbB receptors and their ligands in the breast.
AB  - ErbB receptor tyrosine kinases are membrane-bound receptors that possess
      intrinsic, ligand-activated, tyrosine kinase activity. Binding of growth factors
      to these receptors induces the formation of ErbB homo- and heterodimers and
      initiates a signalling cascade that traverses the cytoplasm to communicate with
      the nucleus and the cytoskeleton. The effect of this cascade is the regulation of
      cellular proliferation, differentiation, apoptosis, migration and adhesion.
      Although ErbB signalling is important for normal growth and development in the
      breast, a dysregulation of ErbB activity can lead to tumourigenesis. This review
      will focus on the role of ErbB signalling in both normal mammary gland
      development and breast cancer, with an emphasis on the mechanisms behind receptor
      activation and the therapeutic agents designed to inhibit ErbB activity.

PMID- 16984693
TI  - Current options, and long-term results for interventional treatment of pulmonary
      valvar stenosis.

PMID- 16984694
TI  - Aortic dissection in Turner's syndrome: a "perfect storm"?

PMID- 16984695
TI  - Clinical and epidemiological description of aortic dissection in Turner's
      syndrome.
AB  - BACKGROUND: Women with Turner's syndrome have an increased risk of congenital
      cardiac malformations, ischaemic heart disease, hypertension and stroke. Aortic
      dissection seems to occur with increased frequency. AIM: To describe in more
      detail aortic dissection as encountered in Turner's syndrome, giving attention to
      clinical, histological and epidemiological aspects. MATERIALS AND METHODS: Based
      on a retrospective study, we describe the clinical, karyotypic, and
      epidemiological aspects of aortic dissection as encountered in cases of Turner's
      syndrome seen in Denmark and Sweden. RESULTS: The median age at onset of aortic
      dissection in 18 women was 35 years, ranging from 18 to 61 years. Fourteen of 18
      women had a 45,X karyotype, while 2 patients had 45,X/45,XY, and 2 had the
      45,X/46,X+r(X) complement, respectively. Echocardiography was performed in 10 of
      18 patients before their acute illness, and showed signs of congenital cardiac
      disease, with either bifoliate aortic valves, dilation of the aortic root, or
      previous aortic coarctation evident in most patients. In 5 patients evidence of a
      bifoliate aortic valve was conclusive. Hypertension was present in 5 of 18
      patients, while 10 of the patients died from aortic dissection, of so-called type
      A in 6, type B in 3, while in the final case the origin of dissection could not
      be determined. Biochemical analysis showed altered ratio between type I and type
      III collagen. Histology showed cystic medial necrosis in 3 of 7 cases. We
      estimated an incidence of dissection of 36 per 100,000 Turner's syndrome years,
      compared with an incidence of 6 per 100,000 in the general population, and a
      cumulated rate of incidence of 14, 73, 78, and 50 per 100,000 among 0-19, 20-29,
      30-39, and 40+ year olds, respectively. CONCLUSION: Aortic dissection is
      extremely common in the setting of Turner's syndrome, and occurs early in life.
      Patients with Turner's syndrome should be offered a protocol for clinical follow
      up similar to that provided for patients with Marfan syndrome, and each clinic
      should embrace a programme for follow-up.

PMID- 16984696
TI  - The diverse cardiac morphology seen in hearts with isomerism of the atrial
      appendages with reference to the disposition of the specialised conduction
      system.
AB  - Congenital cardiac malformations which include isomerism of the atrial appendages
      are amongst the most challenging of problems for diagnosis and also for medical
      and surgical management. The nomenclature for pathological description is
      controversial, but difficulties can be overcome by the use of a segmental
      approach. Such an approach sets out the morphology and the topology of the
      chambers of the heart, together with the types and modes of the atrioventricular,
      ventriculo-arterial, and venous connections. We have applied this method to a
      study of 35 hearts known to have isomerism of the atrial appendages. We have
      already published accounts of 27 of these cases, but these were reviewed for this
      study in the light of our increased awareness of the implications of isomerism,
      and 8 new cases were added. After examining, or re-examining, the morphology of
      every heart in detail, we grouped them together according to their ventricular
      topology and modes of atrioventricular connection. Then we studied the course of
      the specialised conduction system, by the use of the light microscope, first in
      each individual case, and then together in their groups. We conclude that the
      pathways for atrioventricular conduction in hearts with isomerism of the atrial
      appendages are conditioned both by ventricular topology, and by the
      atrioventricular connections. Based on our experience, we have been able to
      establish guidelines that direct the clinician to the likely location of the
      conduction tissues.

PMID- 16984697
TI  - Experience with intraoperative ultrasound in paediatric cardiac surgery.
AB  - OBJECTIVE: Intraoperative ultrasound was introduced to evaluate the adequacy of
      repair after surgical repair of congenital cardiac malformations. Our purpose was
      to review the evolution of this technique at our centre. METHODS: We evaluated
      all intraoperative ultrasound studies undertaken between 1997 and 2002, reviewing
      the data from 1997 through 2001 retrospectively, but undertaking a prospective
      audit of studies undertaken from 2002 onwards. In all, we carried out a total
      number of 639 intraoperative ultrasound studies, from a possible 2737 cardiac
      operations (23.3%), using the epicardial approach in 580 (90.7%), and
      transoesophageal ultrasound in the other 59 patients (9.3%). Median age was 0.6
      years, with an interquartile range from 0.06 to 3.6 years. RESULTS: The findings
      obtained using intraoperative ultrasound influenced the surgical management in 63
      of the 639 patients (9.9%), suggesting the need for additional surgery in 26,
      adjustment of the band placed round the pulmonary trunk in 16, preoperative
      assessment of the cardiac malformation in 5, and confirming the need for
      prolonged support with cardiopulmonary bypass for impaired ventricular function
      in 16. There were 18 early reoperations, 5 of which may have been predicted by
      intraoperative ultrasound. Of the 183 studies reviewed prospectively in 2002, it
      was not possible to obtain the complete range of views in 8 (4.4%), while in 27
      patients (14.7%), the postoperative findings using transthoracic interrogation
      differed from the findings obtained immediately following bypass. CONCLUSION:
      Intraoperative ultrasound is an important technique for monitoring the results of
      complex congenital cardiac surgery. The immediate recognition of significant
      lesions, together with multidisciplinary discussion, allows for improved
      management and prevention of early surgical reintervention.

PMID- 16984698
TI  - Criterions for selection of patients for, and results of, a new technique for
      construction of the modified Blalock-Taussig shunt.
AB  - BACKGROUND: We describe alternative surgical techniques for construction of
      systemic-to-pulmonary arterial shunts, and propose criterions for their
      application in selected patients. PATIENTS AND METHODS: We constructed a variety
      of modified systemic-to-pulmonary arterial shunts, using polytetrafluoroethylene
      grafts, in 92 selected patients with cyanotic congenital heart disease and
      anomalies of the aortic arch and systemic veins. Their age ranged from 7 days to
      3.6 years, with a mean of 7.08 months. We performed 88 operations through a
      thoracotomy. Of this cohort, 60 patients underwent a second-stage operation, with
      15 receiving a superior cavopulmonary connection, 16 a total cavopulmonary
      connection, and 29 proceeding to biventricular repair after a mean interval of
      15.6 months. We have 21 patients awaiting their second or final stage of
      palliation. RESULTS: There were five early (5.4%) and six late deaths (6.8%), two
      of which were related to construction of the shunts. At a mean follow-up of 45.29
      months, the increase in diameter of pulmonary trunk and its right and left
      branches was uniform and significant (p value less than 0.001). Pulmonary
      arterial distortion requiring correction at the time of second-stage operation
      was observed in 5 patients (6.1%). Adequate overall palliation was achieved in
      98% of the cohort at 8 months, 91% at 12 months, and 58% at 18 months.
      CONCLUSIONS: Patients with a right- or left-sided aortic arch and right-sided
      descending thoracic aorta, those with anomalies of systemic venous drainage
      masking the origin of great arterial branches, and those with disproportionately
      small subclavian arteries, constitute the ideal candidates for our suggested
      modification of the construction of a modified Blalock-Taussig shunt. The
      palliation provided by these shunts was satisfactory, with predictable growth of
      pulmonary arteries, insignificant distortion in the great majority, and easy take
      down.

PMID- 16984699
TI  - Who benefits from intervention in, as opposed to screening of, overweight and
      obese children?
AB  - AIMS: StEP TWO is a school- and family-based intervention consisting of extra
      lessons, healthy nutrition and physical education for overweight and obese
      children in primary schools, aimed at reducing body mass index by maintenance or
      reduction of weight, and improving motor abilities. We analysed differences in
      changes in anthropometric, cardiovascular and obesity parameters between children
      who underwent intervention, non-participants in intervention, and controls.
      METHODS: Anthropometric data and waist circumference were recorded for 1678
      children; body mass index and body mass index-standard deviation score were
      calculated. Blood pressure was measured after 5 minutes at rest. 121 overweight
      and obese children enrolled at 3 schools involved in programmes of intervention
      were invited to take part; 40 of them completed the programme from November 2003
      to July 2004. Of these overweight children, 74 were invited, but did not take
      part. As controls, we enrolled 155 overweight and obese children from 4 other
      schools. RESULTS: After the programme, the children involved in intervention
      showed a lower increase in the body mass index (0.3 plus or minus 1.3 versus 0.7
      plus or minus 1.2 kilograms per metre squared) and an approximately three times
      higher diminution of the body mass index-standard deviation score in comparison
      with their controls (-0.15 plus or minus 0.26 versus 0.05 plus or minus 0.27).
      Systolic blood pressure was significantly lowered by 9.5 plus or minus 19.6
      millimetres of mercury in those involved in intervention, but increased in the
      control group by 0.5 plus or minus 16.5 millimetres of mercury. Among those
      invited but not participating, the increase of the body mass index (0.5 plus or
      minus 1.3 kilograms per metre squared) was less, and the reduction of the body
      mass index-standard deviation score (-0.09 plus or minus 0.31) and systolic blood
      pressure (-5.3 plus or minus 15.6 millimetres of mercury) was higher than in the
      control group. Overweight but not obese children seem to benefit from a screening
      examination alone. CONCLUSIONS: Early preventive measures in schools are
      necessary and effective for overweight and obese primary school children. The
      screening itself seems also to have a minor positive effect, especially for
      overweight children. Sustainability of the observed improvements over a longer
      period remains to be confirmed.

PMID- 16984700
TI  - Neo-aortic valvar function after the arterial switch.
AB  - OBJECTIVES: The purpose of our study was to assess the prevalence and
      progression, during childhood and adolescence, of dilation of the neo-aortic
      root, and neo-aortic valvar regurgitation, and to identify risk factors for such
      dilation and regurgitation, after the arterial switch operation. METHODS: We
      included all patients who had undergone an arterial switch operation at The
      Children's Hospital of Philadelphia, and had been followed for a minimum of 4
      years, and had at least 2 postoperative echocardiograms. Neo-aortic valvar
      regurgitation was quantitatively assessed, and measurements were made of the neo
      aortic root at the level of the basal attachment of the leaflets, mid-sinusal
      level, and the sinutubular junction. RESULTS: We found 82 patients who satisfied
      the criterions for inclusion, of whom 52 patients had transposition with an
      intact ventricular septum, and 30 had either an associated ventricular septal
      defect or double outlet right ventricle. The median follow-up time was 8.8 years
      (4.1 to 16.4 years). The neo-aortic valve had been replaced in 1 patient. Of the
      patients, 3 had moderate, 66 had trivial to mild, and 12 had no neo-aortic valvar
      regurgitation at their most recent follow-up. The regurgitation had progressed by
      at least 1 grade in 38 of the 82 patients (46.4%). Neo-aortic dilation was noted
      at the basal attachment of the leaflets, and at mid-sinusal level, which was out
      of proportion to somatic growth. CONCLUSIONS: At mid-term follow-up, significant
      neo-aortic valve regurgitation is present in 3.7%, and trivial to mild
      regurgitation in 81.4% of patients. The regurgitation progressed in almost half
      of the patients over time. We also noted progressive dilation of the neo-aortic
      root out of proportion to somatic growth.

PMID- 16984701
TI  - Correlations with operative anatomy of real time three-dimensional
      echocardiographic imaging of congenital aortic valvar stenosis.
AB  - OBJECTIVE: To define the anatomic characteristics of the congenitally malformed
      and severely stenotic aortic valve using trans-thoracic real time three
      dimensional echocardiography, and to compare and contrast this with the valvar
      morphology as seen at surgery. DESIGN: Prospective cross-sectional observational
      study. SETTING: Tertiary centre for paediatric cardiology. METHODS: All patients
      requiring aortic valvotomy between December 2003 and July 2004 were evaluated
      prior to surgery with three-dimensional echocardiography. Full volume loop images
      were acquired using the Phillips Sonos 7500 system. A single observer analysed
      the images using "Q lab 4.1" software. The details were then compared with
      operative findings. RESULTS: We identified 8 consecutive patients, with a median
      age of 16 weeks, ranging from 1 day to 11 years, with median weight of 7.22
      kilograms, ranging from 2.78 to 22 kilograms. The measured diameter of the valvar
      orifice, and the number of leaflets identified, corresponded closely with
      surgical assessment. The sites of fusion of the leaflets were correctly
      identified by the echocardiographic imaging in all cases. Fusion between the
      right and non-coronary leaflets was identified in half the patients. Dysplasia
      was observed in 3 patients, with 1 patient having nodules and 2 shown to have
      excrescences. At surgery, nodules were excised, and excrescences were trimmed.
      The dysplastic changes correlated well with operative findings, though
      statistically not significant. CONCLUSION: We recommend trans-thoracic real time
      three-dimensional echocardiography for the assessment of the congenitally
      malformed aortic valve, particularly to identify sites of fusion between leaflets
      and to measure the orificial diameter. The definition of nodularity, and the
      prognosis of nodules based on the mode of intervention, will need a comparative
      study of patients submitted to balloon dilation as well as those undergoing
      surgical valvotomy.

PMID- 16984702
TI  - Fibromuscular dysplasia as the substrate for systemic and pulmonary hypertension
      in the setting of Moya-Moya disease.
AB  - We report the first case, to the best of our knowledge, of a child with the
      unusual association of Moya-Moya disease and both systemic and pulmonary
      hypertension. Histological examination revealed fibromuscular dysplasia as the
      common denominator for a diffuse arteriopathy.

PMID- 16984703
TI  - Terminal arrhythmia in a patient with Mustard's operation.
AB  - In spite of significant improvements in outcome, adults surviving the Mustard
      procedure continue to be at risk of premature death, cardiac failure, and
      arrhythmias. Primary ventricular fibrillation as a cause of sudden death in these
      patients may not be uncommon, and implantation of a defibrillator should be
      considered, particularly if there is systemic ventricular dysfunction and pre
      existing heart block.

PMID- 16984704
TI  - Anomalous origin of the right coronary artery from the left anterior
      interventricular coronary artery in the setting of tetralogy of Fallot.
AB  - We describe anomalous origin of the right coronary artery from the left anterior
      interventricular coronary artery in a 16-year-old female with tetralogy of
      Fallot, highlighting the rarity and surgical significance of this anomaly.

PMID- 16984705
TI  - The management of hypoplastic left heart syndrome with a right aortic arch.
AB  - The combination of hypoplastic left heart syndrome and a right-sided aortic arch
      is extremely rare and lethal. To the best of our knowledge, no patient with this
      combination has previously been reported as surviving initial palliation. The
      anatomic variant is associated with abnormalities in the arteries branching from
      the aortic arch, making it difficult to construct a reliable source of flow of
      blood to the lungs. We present here a patient with this combination who survived
      an initial Damus-Kay-Stansel procedure combined with placement of a conduit from
      the right ventricle to the pulmonary arteries, and who has subsequently undergone
      a successful bidirectional cavopulmonary anastomosis. We believe that the conduit
      placed from the right ventricle provides the most reliable source of flow of
      blood to the lungs at the time of initial palliation in this usual combination of
      cardiac lesions.

PMID- 16984706
TI  - Successful release of recurrent pulmonary venous obstruction after repair of
      totally anomalous pulmonary venous connection by transcatheter implantation of
      stents.
AB  - We report a 3-month-old female infant, in whom pulmonary venous obstruction
      occurred after repair of totally anomalous pulmonary venous connection, and which
      was successfully released by a transcatheter implantation of a stent using the
      transseptal approach. Close follow-up is required, since the long-term outcome is
      still unclear. Nevertheless, transcatheter implantation of stents is a promising
      option for treating this challenging lesion.

PMID- 16984707
TI  - Giant coronary arterial aneurysms and thrombosis in an infant with Kawasaki
      disease.

PMID- 16984708
TI  - Giant aneurysms of the coronary arteries due to Kawasaki disease--regular review
      without radiation using cardiovascular magnetic resonance.

PMID- 16984709
TI  - Tracheal compression by aortic dilation in double inlet ventricle with pulmonary
      atresia.

PMID- 16984714
TI  - 'They're not racist ...' prejudice denial, mitigation and suppression in
      dialogue.
AB  - Social scientific work on the suppression, mitigation or denial of prejudiced
      attitudes has tended to focus on the strategic self-presentation and self
      monitoring undertaken by individual social actors on their own behalf. In this
      paper, we argue that existing perspectives might usefully be extended to
      incorporate three additional considerations. First, that social actors may, on
      some occasions, act to defend not only themselves, but also others from charges
      of prejudice. Second, that over the course of any social encounter, interactants
      may take joint responsibility for policing conversation and for correcting and
      suppressing the articulation of prejudiced talk. Third, that a focus on the
      dialogic character of conversation affords an appreciation of the ways in which
      the status of any particular utterance, action or event as 'racist' or
      'prejudiced' may constitute a social accomplishment. Finally, we note the logical
      corollary of these observations - that in everyday life, the occurrence of
      'racist discourse' is likely to represent a collaborative accomplishment, the
      responsibility for which is shared jointly between the person of the speaker and
      those other co-present individuals who occasion, reinforce or simply fail to
      suppress it.

PMID- 16984715
TI  - Constructing identities in cyberspace: the case of eating disorders.
AB  - This paper consists of a discourse analysis of data collected from websites that
      have been created by and for people who wish to share experiences of eating
      disorders in a positive and supportive environment. These sites have earned the
      broad description 'pro-ana' (where 'ana' is short for 'anorexia'). Site users
      have come to see themselves as a broad on-line community of like-minded
      individuals, but within this community there are many subgroups, and the
      boundaries between these subgroups are fiercely contested. In addition, frequent
      attacks on such websites in the media (charged with 'promoting eating
      disorders'), and by occasional hostile site visitors, have often forced the
      community into a defensive mode. The result is a rich tapestry of identity work.
      The analysis examines several 'pro-ana' sites and explores the way in which the
      identity is used to police the boundaries of the community, and ultimately, what
      it means 'to be ana' rather than 'mia' (bulimic), 'a normal', 'a faker', or even
      'a hater'.

PMID- 16984716
TI  - Social identity and the recognition of creativity in groups.
AB  - This paper develops an analysis of creativity that is informed by the social
      identity approach. Two studies are reported that support this analysis. Study 1
      (N=73) manipulated social identity salience and the content of group norms. The
      group norm was either conservative (i.e. promoted no change) or progressive (i.e.
      promoted change). When social identity was salient and the group norm was
      conservative, a non-novel proposal was perceived to be more creative. Study 2
      (N=63) manipulated social norms and identity relevance. Results showed that while
      social norms influenced perceptions of creativity, identity relevance influenced
      positivity but not perceptions of creativity. These findings support the idea
      that perceptions of creativity are grounded in the normative content of group
      membership and self-categorization processes.

PMID- 16984717
TI  - Self-evaluation in a naturalistic context: the case of juvenile offenders.
AB  - The authors investigated how self-evaluation motives (self-enhancement, self
      assessment, self-verification, self-improvement - and also self-diminishment and
      no information) shape self-knowledge preferences in male incarcerated juvenile
      offenders (IJOs). IJOs responded to questions on how much they would like to
      receive and actually received each of six types of feedback (positive, truthful,
      improving, consistent, negative and no feedback) from each of six sources
      (teachers, parents, siblings, best friend, girlfriend and behavioural specialists
      or psychologists). IJOs disliked negative feedback and the lack of feedback. They
      preferred truthful feedback to consistent feedback, and received truthful and
      positive feedback more frequently than improving feedback. Additionally, they
      received more negative or no feedback from parents than they would like. Finally,
      IJOs expressed a preference for receiving more improving feedback from their
      girlfriends than they did. The study highlights the interplay of self-evaluation
      motives in IJOs and opens up promising research and rehabilitation directions.

PMID- 16984718
TI  - People's responses to upward and downward social comparisons: the role of the
      individual's effort-performance expectancy.
AB  - The aim of this research among practicing teachers was to demonstrate that the
      individual's effort-performance (E-P) expectancy can explain different responses
      to upward and downward social comparison information in terms of positive affect
      and the intent to work harder. The results of both Experiment 1 (N=100) and
      Experiment 2 (N=162) show that exposure to a superior colleague generated more
      positive affect among teachers than exposure to an inferior other, particularly
      at high levels of E-P expectancy. Perhaps more importantly, explaining target's
      superior performance in terms of high effort and inferior performance in terms of
      low effort enhanced participants' intentions to work harder at their own jobs.

PMID- 16984719
TI  - The added value of respect: reaching across inequality.
AB  - The experiment (N=80) tested whether the effectiveness of intragroup respect is
      moderated by structural (in)equality between the self and the rest of one's
      group. Equality (restricted vs. full rights) and respect (disrespect vs. respect)
      were manipulated as independent variables, while collective identification and
      willingness to engage in group-serving behaviour were the main dependent
      variables. Moderation was confirmed such that the positive effects of respect
      were more pronounced among group members with restricted rights than among group
      members with full rights. Moreover, respect fully compensated for the initial
      deficit in self-perception as a fully fledged group member. However, there was
      also some indication that, when money is at stake, formal guarantees of equality
      may be necessary for respect to have a facilitative effect on individual
      sacrifices for the sake of the group. The practical and political implications of
      the results are discussed.

PMID- 16984720
TI  - Three ways to forgive: a numerically aided phenomenological study.
AB  - The topic of forgiveness has received increased attention in the psychological
      literature; however, definitional and operational clarity remains a stumbling
      block. We propose that the study of first-person experiential accounts can enrich
      ongoing definitional and psychometric efforts. We systematically examined such
      accounts of forgiveness, identifying recurrent themes and then clustering these
      accounts according to similarities in theme profiles. People reported forgiveness
      through interpersonal confrontation with their transgressor (Cluster I), intra
      personal evaluation of human fallibility and moral commitments (Cluster II), and
      attempts to resume a positive relationship without presuming that the
      transgression could be ignored or forgotten (Cluster III). The findings of the
      present research help to integrate recent studies of forgiveness, and the
      implications of a tripartite model of forgiveness are considered.

PMID- 16984721
TI  - Invited and uninvited applause in political speeches.
AB  - According to Atkinson (e.g. 1983, 1984a, 1984b), a limited range of rhetorical
      devices are consistently used by political speakers to invite audience applause.
      A detailed review is presented of the research literature relevant to Atkinson's
      analysis, including a series of evaluative studies conducted by the author. From
      this review, it is argued that Atkinson overestimated the role of rhetorical
      devices in inviting applause and underestimated the significance of other
      features, such as asynchronous applause, speech delivery, speech content and
      uninvited applause. To integrate these features, a re-conceptualisation is
      presented of how audience applause occurs in political speeches, based on a
      fundamental distinction between invited and uninvited applause.

PMID- 16984722
TI  - The influence of biological sex, sexuality and gender role on interpersonal
      distance.
AB  - This research reports on a conceptually and methodologically innovative study,
      which sought to measure the influence of gender on interpersonal distance. In so
      doing, we argue for an important distinction to be made between biological sex,
      gender role, and sexuality. To date, however, progress in the study of
      interpersonal distance (IPD) has been inhibited by poor operational definitions
      and inadequate measurement methodologies. For our own investigation, we innovated
      on methodology by devising the digital video-recording IPD method (DiVRID) that
      records interpersonal spatial relationships using high quality digital video
      equipment. The findings highlighted not only the validity of our innovative
      method of investigation, but also that a more sophisticated conceptualization of
      the impact of gender on IPD is warranted than can be accounted for by biological
      sex differences. In this study, we found that gender role accounts for more of
      the variation in IPD than the conventionally reported gender variable, sex.

PMID- 16984723
TI  - Support provider's appraisal detection bias and the efficacy of received support
      in medical students preparing for an exam.
AB  - Matching social support to the recipient's needs requires diagnostic sensitivity
      on the part of the provider. In particular, support needs to be responsive to the
      recipient's stress-related appraisals to be maximally effective. To assess the
      impact of bias in interpersonal stress assessment, medical students in 43 dyads
      reported on their own and each other's stress appraisals, social support, affect
      and performance during a 5-day preparation period culminating in a multiple
      choice examination. Less biased perceptions of loss appraisals by support
      providers within dyads were followed by support transactions associated with
      lower negative affect and better exam performance among recipients. More biased
      perceptions of threat appraisals were followed by increases in the recipients'
      negative affect. Results therefore suggest that support is more effective when
      the provider understands the recipient's concerns.

PMID- 16984724
TI  - Perceptions of empathic accuracy and assumed similarity in the coach-athlete
      relationship.
AB  - Drawing upon the methodology developed by Kenny and Acitelli (2001), this study
      examined empathic accuracy and assumed similarity in both parties' perceptions of
      coach-athlete relationships. One hundred and twenty-one coaches and athletes
      reported on their direct-perceptions and meta-perceptions of closeness,
      commitment and complementarity (3 Cs; Jowett & Cockerill, 2002), and of
      satisfaction with instruction, performance and external agents. There was
      evidence of both empathic accuracy and assumed similarity in coaches' and
      athletes' perceptions. Athletes were more accurate in identifying the specific
      content of their coaches' feelings in terms of closeness. Athletes and coaches
      from newly developed relationships displayed higher levels of empathic accuracy,
      whereas female athletes displayed higher levels of assumed similarity. Moreover,
      evidence suggested that athletes' and coaches' assumed similarity led to more
      accurate perceptions. Implications and future research directions are discussed.

PMID- 16984725
TI  - Beyond frequency: habit as mental construct.
AB  - Progress in habit theory can be made by distinguishing habit from frequency of
      occurrence, and using independent measures for these constructs. This proposition
      was investigated in three studies using a longitudinal, cross-sectional and
      experimental design on eating, mental habits and word processing, respectively.
      In Study 1, snacking habit and past snacking frequency independently predicted
      later snacking behaviour, while controlling for the theory of planned behaviour
      variables. Habit fully mediated the effect of past on later behaviour. In Study
      2, habitual negative self-thinking and past frequency of negative self-thoughts
      independently predicted self-esteem and the presence of depressive and anxiety
      symptoms. In Study 3, habit varied as a function of experimentally manipulated
      task complexity, while behavioural frequency was held constant. Taken together,
      while repetition is necessary for habits to develop, these studies demonstrate
      that habit should not be equated with frequency of occurrence, but rather should
      be considered as a mental construct involving features of automaticity, such as
      lack of awareness, difficulty to control and mental efficiency.

PMID- 16984726
TI  - Preoperative plasma transcript AA454543 level is an independent prognostic factor
      for hepatocellular carcinoma after partial hepatectomy.
AB  - BACKGROUND: We have previously reported that tissue expression levels of
      transcript AA454543 in hepatocellular carcinoma (HCC) are significantly higher
      than those of normal livers, livers with cirrhosis, and livers with hepatitis. In
      addition, a higher level of transcript AA454543 in tumor tissues is associated
      with poor prognosis. We aim to examine whether quantitative measurement of
      preoperative plasma transcript AA454543 can provide similar prognostic
      information. PATIENTS AND METHODS: Blood samples were obtained from 84 HCC
      patients before surgery. Real-time quantitative reverse transcription-polymerase
      chain reaction, using TaqMan system, was employed to measure plasma transcript
      AA454543 and alpha-fetoprotein (AFP) RNA levels. We assessed their prediction
      power in prognosis using univariate and multivariate analyses. RESULTS: High
      plasma transcript AA454543 RNA levels were associated with poor overall survival
      (log-rank test, P < .01). Patients with different plasma AFP RNA levels revealed
      no difference in overall survival (log-rank test, P = .88). By multivariate Cox
      regression analysis, plasma transcript AA454543 RNA level (hazard ratio = 4.8, P
      < .01) and tumor stage (hazard ratio = 1.7, P < .01) were determined to be
      independent risk factors for the prediction of overall survival. CONCLUSION:
      Preoperative plasma transcript AA454543 RNA level can provide prognostic
      information for HCC patients receiving curative partial hepatectomy.

PMID- 16984727
TI  - c-myc amplification is frequent in esophageal adenocarcinoma and correlated with
      the upregulation of VEGF-A expression.
AB  - BACKGROUND: Deregulation of c-myc plays a major role in the carcinogenesis of
      human malignancies. We investigated the amplification of the c-myc gene in a
      surgical series of Barrett cancers. METHODS: Primary resected esophageal
      (Barrett) adenocarcinomas (n = 84) were investigated for c-myc amplification
      using chromogene in situ hybridization. Tumor samples were assembled in a tissue
      microarray. c-myc gene dosage was correlated with clinicopathologic parameters,
      including the survival and gene expression of cyclooxygenases (COX-1 and COX-2)
      and proangiogenic growth factors (VEGF-A and VEGF-C). RESULTS: The majority (70
      of 84; 83.3%) exhibited amplification of the c-myc gene. There were low-level
      amplifications in 63 (75.0%) cases and high-level amplifications in 7 (8.3%)
      cases. No amplification was found in 14 (16.7%) cases. Tumors without c-myc
      amplification had lower VEGF-A, VEGF-C, and COX-2 expression levels than tumors
      with low-level and high-level c-myc amplification (statistically significant for
      VEGF-A; P = .0348). c-myc amplification was not correlated with
      clinicopathological parameters or survival. Only diffuse and mixed-type tumors,
      according to Lauren classification, exhibited c-myc amplifications more
      frequently (P = .0466). CONCLUSIONS: Amplifications of the c-myc gene are
      frequent in Barrett cancer. c-myc may be involved in the regulation of
      angiogenesis.

PMID- 16984728
TI  - Inflammation and atrophy precede prostatic neoplasia in a PhIP-induced rat model.
AB  - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a
      major mutagenic heterocyclic amine in the human diet and is carcinogenic in the
      rat prostate. To validate PhIP-induced rat prostatic neoplasia as a model of
      human prostate cancer progression, we sought to study the earliest histologic and
      morphologic changes in the prostate and to follow progressive changes over time.
      We fed sixty-seven 5-week-old male Fischer F344 rats with PhIP (400 ppm) or
      control diets for 20 weeks, and then sacrificed animals for histomorphologic
      examination at the ages of 25, 45, and 65 weeks. Animals treated with PhIP showed
      significantly more inflammation (P = .002, > .001, and .016 for 25, 45, and 65
      weeks, respectively) and atrophy (P = .003, > .001, and .006 for 25, 45, and 65
      weeks, respectively) in their prostate glands relative to controls. Prostatic
      intraepithelial neoplasia (PIN) occurred only in PhIP-treated rats. PIN lesions
      arose in areas of glandular atrophy, most often in the ventral prostate. Atypical
      cells in areas of atrophy show loss of glutathione S-transferase pi
      immunostaining preceding the development of PIN. None of the animals in this
      study developed invasive carcinomas, differing from those in previous reports.
      Overall, these findings suggest that the pathogenesis of prostatic neoplasia in
      the PhIP-treated rat prostate proceeds from inflammation to postinflammatory
      proliferative atrophy to PIN.

PMID- 16984729
TI  - Multiple tumor types may originate from bone marrow-derived cells.
AB  - It was believed that tumors originated from the transformation of their tissue
      specific stem cells. However, bone marrow-derived cells (BMDCs), which possess an
      unexpected degree of plasticity and often reside in other tissues, might also
      represent a potential source of malignancy. To study whether BMDCs play a role in
      the source of other tumors, BMDCs from mice were treated with 3-methycholanthrene
      until malignant transformation was achieved. Here we show that transformed BMDCs
      could form many tumor types, including epithelial tumors, neural tumors, muscular
      tumors, tumors of fibroblasts, blood vessel endothelial tumors, and tumors of
      poor differentiation in vivo. Moreover, a single transformed BMDC has the ability
      to self-renew, differentiate spontaneously into various types of tumor cells in
      vitro, express markers associated with multipotency, and form teratoma in vivo.
      These data suggest that multipotent cancer stem cells seemed to originate from
      transformed BMDCs. Conclusively, these findings reveal that BMDCs might be a
      source of many tumor types, even teratoma. In addition, multipotent cancer stem
      cells might originate from malignant transformed BMDCs.

PMID- 16984730
TI  - Endothelin receptor A blockade enhances taxane effects in prostate cancer.
AB  - Endothelin (ET) 1 is important in the growth of prostate cancer cells through the
      activation of the endothelin A (ET(A)) receptor. ET receptor blockade is a new
      therapeutic target in treating advanced prostate cancer. This study investigates
      the impact of the combination of the ET(A) antagonist atrasentan (ABT-627) and
      taxane chemotherapy on prostate cancer cell survival in vitro and on the delay of
      prostate cancer in a xenograft mouse model. In vitro, PPC-1 cells transfected
      with an ET(A)-overexpressing vector were treated with ABT-627,
      paclitaxel/docetaxel, or both. Clonogenic viability and cell death assays were
      used to determine cell survival and apoptosis, respectively. ABT-627 and
      docetaxel combination treatment was used in vivo to treat mice with established
      ET(A)-overexpressing PPC-1 xenograft tumors, and tumor growth rates were
      assessed. Cell proliferation and vascularity were determined with Ki-67 and CD31
      staining, respectively. Cells treated with combination therapy had significantly
      fewer viable cells and more programmed cell death than cells given monotherapy.
      Xenograft tumor growth rates were significantly lower in mice treated with
      combination therapy than in animals given a single agent. Ki-67 immunostaining
      demonstrated significantly fewer proliferative cells following combination
      therapy than following monotherapy. This study demonstrates ABT-627 to have
      additive antitumor effects when used in combination with taxane drugs both in
      vitro and in vivo.

PMID- 16984731
TI  - Molecular cross-talk between the NFkappaB and STAT3 signaling pathways in head
      and neck squamous cell carcinoma.
AB  - The development of head and neck squamous cell carcinoma (HNSCC) involves the
      accumulation of genetic and epigenetic alterations in tumor-suppressor proteins,
      together with the persistent activation of growth-promoting signaling pathways.
      The activation of epidermal growth factor receptor (EGFR) is a frequent event in
      HNSCC. However, EGFR-independent mechanisms also contribute to the activation of
      key intracellular signaling routes, including signal transducer and activator of
      transcription-3 (STAT3), nuclear factor kappaB (NFkappaB), and Akt. Indeed, the
      autocrine activation of the gp130 cytokine receptor in HNSCC cells by tumor
      released cytokines, such as IL-6, can result in the EGFR-independent activation
      of STAT3. In this study, we explored the nature of the molecular mechanism
      underlying enhanced IL-6 secretion in HNSCC cells. We found that HNSCC cells
      display an increased activity of the IL-6 promoter, which is dependent on the
      presence of an intact NFkappaB site. Furthermore, NFkappaB inhibition
      downregulated IL-6 gene and protein expression, and decreased the release of
      multiple cytokines. Interestingly, interfering with NFkappaB function also
      prevented the autocrine/paracrine activation of STAT3 in HNSCC cells. These
      findings demonstrate a cross-talk between the NFkappaB and the STAT3 signaling
      systems, and support the emerging notion that HNSCC results from the aberrant
      activity of a signaling network.

PMID- 16984732
TI  - Targeting receptor tyrosine kinase on lymphatic endothelial cells for the therapy
      of colon cancer lymph node metastasis.
AB  - Oral treatment with the dual-receptor tyrosine kinase inhibitor AEE788
      effectively reduces the number of peritumoral lymphatic vessels and the incidence
      of lymph node metastasis in nude mice with human HT29 colon cancer cells growing
      in the cecum. Whether inhibition of lymph node metastasis in colon cancer can be
      achieved by directly targeting lymphatic endothelial cells remains unclear. Using
      a microsurgical approach, we generated conditionally immortalized lymphatic
      endothelial cell lines from the H-2K(b)-tsA58 mouse mesentery and characterized
      these cells for the expression of lymphatic endothelial cell markers. Lymphatic
      endothelial cells were stimulated in culture with an array of tumor cell-produced
      cytokines, leading to the identification of redundant pathways for proliferation
      and survival. Treatment with AEE788 decreased the migration, proliferation, and
      survival of lymphatic endothelial cells, demonstrating that oral treatment with
      AEE788 effectively decreases the incidence of colon cancer lymphatic metastasis
      due, in part, to the direct inhibition of lymphatic endothelial cell signaling.

PMID- 16984733
TI  - Mechanisms of indomethacin-induced alterations in the choline phospholipid
      metabolism of breast cancer cells.
AB  - Human mammary epithelial cells (HMECs) exhibit an increase in phosphocholine (PC)
      and total choline-containing compounds, as well as a switch from high
      glycerophosphocholine (GPC)/low PC to low GPC/high PC, with progression to
      malignant phenotype. The treatment of human breast cancer cells with a
      nonsteroidal anti-inflammatory agent, indomethacin, reverted the high PC/low GPC
      pattern to a low PC/high GPC pattern indicative of a less malignant phenotype,
      supported by decreased invasion. Here, we have characterized mechanisms
      underlying indomethacin-induced alterations in choline membrane metabolism in
      malignant breast cancer cells and nonmalignant HMECs labeled with [1,2
      13C]choline using 1H and 13C magnetic resonance spectroscopy. Microarray gene
      expression analysis was performed to understand the molecular mechanisms
      underlying these changes. In breast cancer cells, indomethacin treatment
      activated phospholipases that, combined with an increased choline phospholipid
      biosynthesis, led to increased GPC and decreased PC levels. However, in
      nonmalignant HMECs, activation of the anabolic pathway alone was detected
      following indomethacin treatment. Following indomethacin treatment in breast
      cancer cells, several candidate genes, such as interleukin 8, NGFB, CSF2, RHOB,
      EDN1, and JUNB, were differentially expressed, which may have contributed to
      changes in choline metabolism through secondary effects or signaling cascades
      leading to changes in enzyme activity.

PMID- 16984734
TI  - In vivo selection of phage for the optical imaging of PC-3 human prostate
      carcinoma in mice.
AB  - There is an increasing medical need to detect and spatially localize early and
      aggressive forms of prostate cancer. Affinity ligands derived from bacteriophage
      (phage) library screens can be developed to molecularly target prostate cancer
      with fluorochromes for optical imaging. Toward this goal, we used in vivo phage
      display and a newly described micropanning assay to select for phage that
      extravasate and bind human PC-3 prostate carcinoma xenografts in severe combined
      immune deficiency mice. One resulting phage clone (G1) displaying the peptide
      sequence IAGLATPGWSHWLAL was fluorescently labeled with the near-infrared
      fluorophore AlexaFluor 680 and was evaluated both in vitro and in vivo for its
      ability to bind and target PC-3 prostate carcinomas. The fluorescently labeled
      phage clone (G1) had a tumor-to-muscle ratio of approximately 30 in experiments.
      In addition, prostate tumors (PC-3) were readily detectable by optical-imaging
      methods. These results show proof of principle that disease-specific library
      derived fluorescent probes can be rapidly developed for use in the early
      detection of cancers by optical means.

PMID- 16984735
TI  - Neurotensin phosphorylates GSK-3alpha/beta through the activation of PKC in human
      colon cancer cells.
AB  - Neurotensin (NT), a gastrointestinal hormone, binds its receptor [neurotensin
      receptor (NTR)] to regulate the growth of normal and neoplastic intestinal cells;
      molecular mechanisms remain largely undefined. Glycogen synthase kinase-3 (GSK-3)
      regulates diverse cellular processes, including cell growth and apoptosis. Here,
      we show that NT induces the phosphorylation of GSK-3alpha/beta in the human colon
      cancer cell line HT29, HCT116, or SW480, which possesses high-affinity NTR. The
      effect of NT was blocked by inhibitors of protein kinase C (PKC), but not by
      inhibitors of MEK1 or phosphatidylinositol-3 kinase, suggesting a predominant
      role for PKC in GSK-3beta phosphorylation by NT. Pretreatment with Go6976 (which
      inhibits PKCalpha and PKCbeta1) or downregulation of endogenous PKCalpha or
      PKCbeta1 blocked NT-mediated GSK-3beta (but not GSK-3alpha) phosphorylation.
      Moreover, a selective PKCbeta inhibitor, LY379196, reduced NT-mediated GSK-3beta
      (but not GSK-3alpha) phosphorylation, suggesting a role for PKCbeta1 in the NT
      mediated phosphorylation of GSK-3beta and an undefined kinase in the NT-mediated
      phosphorylation of GSK-3alpha. Treatment with NT or the GSK-3 inhibitor SB216763
      increased the expression of cyclin D1, a downstream effector protein of GSK-3 and
      a critical protein for the proliferation of various cells. Our results indicate
      that NT uses PKC-dependent pathways to modulate GSK-3, which may play a role in
      the NT regulation of intestinal cell growth.

PMID- 16984736
TI  - Dietary antioxidants provide differential subcellular protection in epithelial
      cells.
AB  - This study aimed to evaluate the organelle-specific antioxidant/pro-oxidant
      actions of clinically important dietary antioxidants against oxidative stress. An
      in vitro cellular model was employed to investigate the antioxidant/pro-oxidant
      effects of various concentrations (1, 10 and 100 microM) of ascorbic acid, alpha
      tocopherol and beta-carotene during H2O2-induced oxidative stress. Damage to
      nuclear and mitochondrial genomes was analyzed by quantitative polymerase chain
      reaction and oxidation of membrane lipids was measured via colorimetric assays.
      The key findings were: (i) dietary antioxidants conferred a dose-dependent
      protective effect (with a pro-oxidant shift at higher concentrations); (ii) the
      protection conferred to different sub-cellular organelles is highly specific to
      the dietary antioxidant; (iii) the mtDNA is highly sensitive to oxidative attack
      compared to nDNA (P < 0.05); and (iv) mtDNA protection conferred by dietary
      antioxidants was required to improve protection against oxidative-induced cell
      death. This study shows that antioxidant-induced protection of mtDNA is an
      important target for future oxidative stress therapies.

PMID- 16984737
TI  - Kinetic study on the photostability of riboflavin in the presence of barbituric
      acid.
AB  - The photochemical fate of riboflavin (vitamin B2) in the presence of barbituric
      acid was examined employing polarographic detection of dissolved oxygen and
      steady-state and time-resolved spectroscopy. Under visible light, riboflavin
      reacts with barbituric acid--the latter being transparent to this type of photo
      irradiation--via radicals and reactive oxygen species, such as singlet molecular
      oxygen [O2(1delta(g))] and superoxide radical anion, which are generated from the
      excited triplet state of the vitamin. As a result, both the vitamin and
      barbituric acid are photodegraded. Kinetic and mechanistic studies on the
      photoreactions of riboflavin in the presence of barbituric acid indicate the
      excellent quenching ability of the latter towards O2(1delta(g)).

PMID- 16984738
TI  - Possible mechanism of pesticide toxicity-related oxidative stress leading to
      airway narrowing.
AB  - The study was conducted to assess the magnitude of oxidative stress and lung
      function abnormalities in 34 male pesticide sprayers on exposure to pesticides in
      mango plantations. Biochemical studies on blood antioxidant enzymes revealed an
      unchanged glutathione level and increased level of malondialdehyde (P < 0.001),
      which indicates that pesticide sprayers may have suffered from oxidative stress.
      Decreased acetyl-cholinesterase levels (P < 0.001) in sprayers compared to the
      controls suggest inhibition of cholinesterase activity. The present study shows
      that pesticide toxicity might lead to oxidative stress and airway narrowing
      resulting in decreased peak expiratory flow rate.

PMID- 16984739
TI  - The effect of polyphenolic extract from pine bark, Pycnogenol on the level of
      glutathione in children suffering from attention deficit hyperactivity disorder
      (ADHD).
AB  - Attention deficit hyperactivity disorder (ADHD) belongs to the neurodevelopmental
      disorders characterized by impulsivity, distractibility and hyperactivity. In the
      pathogenesis of ADHD genetic and non-genetic factors play an important role. It
      is assumed that one of non-genetic factors should be oxidative stress.
      Pycnogenol, an extract from the pine bark, consists of bioflavonoids, catechins,
      procyanidins and phenolic acids. Pycnogenol acts as powerful antioxidant,
      chelating agent; it stimulates the activities of some enzymes, like SOD, eNOS,
      and exhibits other biological activities. AIM: The aim of this randomized, double
      blind, placebo-controlled trial was to investigate the influence of administered
      Pycnogenol or placebo on the level of reduced (GSH) and oxidized (GSSG)
      glutathione in children suffering from ADHD and on total antioxidant status
      (TAS). This is the first investigation of the redox glutathione state in relation
      to ADHD. RESULTS: One month of Pycnogenol administration (1 mg/kg body
      weight/day) caused a significant decrease in GSSG and a highly significant
      increase in GSH levels as well as improvement of GSH/GSSG ratio in comparison to
      a group of patients taking a placebo. TAS in children with ADHD was decreased in
      comparison with reference values. Pycnogenol administration normalizes TAS of
      ADHD children.

PMID- 16984740
TI  - Up-regulation of P-glycoprotein expression by catalase via JNK activation in
      HepG2 cells.
AB  - Overexpression of the MDR1 gene is one of the reasons for multidrug resistance
      (MDR). Some studies suggested that antioxidants could down-regulate MDR1
      expression as a possible cancer treatment. In this report, we try to determine
      the effects of antioxidants (catalase or N-acetylcysteine [NAC]) on the
      regulation of intrinsic MDR1 overexpression in HepG2 cells. Adding catalase or N
      acetylcysteine to the HepG2 culture led to a significant increase of MDR1 mRNA
      and P-glycoprotein drug transporter activity. After catalase or NAC treatment, a
      reduced intracellular reactive oxygen species (ROS) was observed. The JNK
      inhibitor SP600125 abolished the positive effects of catalase on drug transporter
      activity in a dose-dependent manner. Furthermore, the up-regulation of P
      glycoprotein functions by catalase was only observed in HepG2 cells but not in
      other cell lines tested (MCF-7, A549, A431). These data suggested that catalase
      can up-regulate P-glycoprotein expression in HepG2 cells via reducing
      intracellular ROS, and JNK may mediate this process.

PMID- 16984741
TI  - Antioxidant activity of L-ascorbic acid in wild-type and superoxide dismutase
      deficient strains of Saccharomyces cerevisiae.
AB  - Much has been published on the non-enzymatic antioxidant L-ascorbic acid (vitamin
      C), but even so its interaction with endogenous cellular defense systems has not
      yet been fully elucidated. Our study investigated the antioxidant activity of L
      ascorbic acid in wild-type strain EG103 (SOD) Saccharomyces cerevisiae and
      isogenic mutant strains deficient in cytosolic superoxide dismutase (sod1delta),
      mitochondrial superoxide dismutase (sod2delta) or both (sod1delta sod2delta),
      metabolizing aerobically or anaerobically with and without the stressing agent
      paraquat. The results show that during both aerobic and anaerobic metabolism
      there was a significant increase in the survival of both wild-type S. cerevisiae
      cells and the mutant cells (sod1delta, sod2delta and sod1delta sod2delta) when
      pretreated with L-ascorbic acid before exposure to paraquat. Exposure to paraquat
      resulted in higher catalase activity but this significantly decreased when the
      cells were pre-treated with L-ascorbic acid. These results demonstrate that due
      to the damage caused by paraquat, the antioxidant protection of L-ascorbic acid
      seems to be mediated by catalase levels in yeast cells.

PMID- 16984742
TI  - Oxygen-related processes in red blood cells exposed to tert-butyl hydroperoxide.
AB  - The correlation between the oxidative processes in tert-butyl hydroperoxide
      (tBHP)-exposed red blood cells and the reactions of oxygen consumption and
      release were investigated. Red blood cell exposure to tBHP resulted in transient
      oxygen release followed by oxygen consumption. The oxygen release in red blood
      cells was associated with intracellular oxyhaemoglobin oxidation. The oxygen
      consumption proceeded in parallel with free radical generation, as registered by
      chemiluminescence, but not to membrane lipid peroxidation. The oxygen consumption
      was also observed in membrane-free haemolyzates. The order of the organic
      hydroperoxide-induced reaction of oxygen release with respect to the oxidant
      (tBHP) was estimated to be 0.9 +/- 0.1 and that of the oxygen consumption
      reaction was determined to be 2.4 +/- 0.2. The apparent activation energy values
      of the oxygen release and oxygen consumption were found to be 107.5 +/- 18.5
      kJ/mol and 71.0 +/- 12.5 kJ/mol, respectively. The apparent pKa value for the
      functional group(s) regulating the cellular oxyHb interaction with the oxidant in
      tBHP-treated red blood cells was estimated to be 6.7 +/- 0.2 and corresponded to
      that of distal histidine protonation in haemoprotein. A strong dependence of tBHP
      induced lipid peroxidation on the oxygen concentration in a red blood cell
      suspension was observed (P50 = 32 +/- 3 mmHg). This dependence correlated with
      the oxygen dissociation curve of cellular haemoglobin. The order of the membrane
      lipid peroxidation reaction with respect to oxygen was found to be 0.5 +/- 0.1.
      We can conclude that the intensity of the biochemical process of membrane lipid
      peroxidation in tBHP-exposed erythrocytes is controlled by small changes in such
      physiological parameters as the oxygen pressure and oxygen affinity of cellular
      haemoglobin. Neither GSH nor oxyhaemoglobin oxidation depended on oxygen
      pressure.

PMID- 16984743
TI  - Relative efficacy of ondansetron, granisetron, dolasetron and palonosetron in
      controlling acute nausea and vomiting associated with platinum-based
      chemotherapy.

PMID- 16984744
TI  - Recent advances in targeted therapies for colorectal cancer.
AB  - BACKGROUND: Recent advances in the molecular biology and genetics of colorectal
      cancer have led to the identification of potential therapeutic targets such as
      epidermal growth factor receptor, vascular endothelial growth factor and
      endothelial receptors. OBJECTIVE: This review will examine the major therapeutic
      advances along with the preclinical basis justifying their combination with
      conventional therapeutic tools. This review will also critically consider current
      possibilities offered to identify responding patients. DATA SOURCES: Preclinical
      and primary clinical trial results published in peer-review journals. The authors
      examined the relevance and subsequent inclusion of the data. CONCLUSIONS:
      Cetuximab and bevacizumab provide new benefits in terms of the response rate and
      survival. There remain, however, important questions concerning, for instance,
      optimal combinations between conventional cytotoxic agents and targeted therapies
      and also between targeted drugs themselves. These new targeted treatments are
      costly and in this context the question of the identification of the right drug
      for the right patient is particularly relevant. Adequate tools in predicting the
      efficacy of targeted treatments are still needed.

PMID- 16984745
TI  - An evaluation of pharmacist contribution to an oncology ward in a Swedish
      hospital.
AB  - AIM: The aim of this project was to establish the importance of a pharmacist in
      the health-care team in improving drug use in an oncology ward in the Department
      of Oncology, Karolinska University Hospital, Stockholm, Sweden. METHODS AND
      PATIENTS: The pharmacist participated in the medical round in the mornings and
      worked as a member of the health-care team. Drug-related problems (DRPs) were
      identified by drug chart reviews based on data from medical files, laboratory
      tests and interviews with patients and/or relatives. A questionnaire to
      physicians and nurses was used to evaluate their experiences of the pharmacist's
      contribution to the oncology ward. RESULTS: In total, 114 DRPs were identified in
      58 patients. For each DRP, the pharmacist gave proposals for solutions. Sixty
      eight suggestions out of 114 (59.6%) were implemented by the physician. Two
      suggestions (1.8%) were partly followed. For 32 suggestions (28.0%) it was
      unclear if they had caused any change in medication. Twelve suggestions (10.5%)
      were not followed. Most of the physicians and nurses acknowledged the
      pharmacist's contribution to improved drug use in the ward. CONCLUSION: A
      pharmacist can improve drug use in an oncology ward as a member of the health
      care team. The pharmacist contributes with a systematic focus on the patient from
      a drug perspective.

PMID- 16984746
TI  - 25 years of safe handling of cytotoxics (antineoplastics) in Israel.
AB  - INTRODUCTION: Israel is a small country, about the size of Wales, located in the
      eastern corner of the Mediterranean Sea. The Israel Ministry of Health has
      responsibility for health matters in Israel. All health matters fall under their
      jurisdiction. HOSPITAL AND CLINICAL PHARMACY IN ISRAEL: There are about 50
      hospitals in Israel with between 300 and 1200 beds including 12 specialist
      tertiary care centres (6 have facilities to perform bone marrow
      transplantations). The total number of hospital beds is around 30,000. SAFE
      HANDLING OF CYTOTOXICS IN ISRAEL: Israel's growing population (rising from half a
      million in 1948 to about 7 million in 2005) has been matched with an equally
      rapid rise in the use of cytotoxic drugs. The ministry issued guidelines to
      standardize and harmonize the level of pharmaceutical oncology services in
      Israel, and improve the professional level of cytotoxic pharmacy services and
      acknowledged the need to recognize clinical oncology pharmacy as a speciality.
      DISCUSSION: Over the last 25 years, safe handling of cytotoxics has moved forward
      in Israel in a manner comparable to that seen in the best of the developed
      "western" countries.

PMID- 16984747
TI  - Defining the clinical improvement in cancer drug therapy: implications for
      priority setting in healthcare.
AB  - An explicit approach to funding decisions has become increasingly important to
      ensure fairness and consistency in resource allocation in cancer therapy. Funding
      decisions are often based on whether a treatment is 'medically necessary' and the
      level of clinical improvement. Currently, there is a lack of consensus on
      defining different levels of clinical improvement, leading to controversies on
      the values placed on different outcomes and degrees of clinical improvements
      during funding evaluation. More information on how clinicians and patients define
      the levels of clinical improvement can help ensure the evaluation and decision
      making processes of funding to become more predictable, consistent,
      understandable and therefore accountable to providers and consumers of
      healthcare.

PMID- 16984748
TI  - Studies on the decontamination of surfaces exposed to cytotoxic drugs in
      chemotherapy workstations.
AB  - OBJECTIVE: The aim of this study was to examine the removal and deactivation of
      cytotoxic contamination from surfaces of a pharmaceutical isolator workstation.
      METHODS: Three marker cytotoxic drugs were evaluated in three phases using
      decontamination technologies currently available in the pharmaceutical and
      healthcare environments. Phase I investigated the physical removal of
      contamination by detergents. Phase II and III investigated the effectiveness of
      detergents and Vaporised Hydrogen Peroxide (VHP) in degrading cytotoxic drugs,
      respectively. RESULTS: 5-Flurouracil, doxorubicin and cyclophosphamide were
      removed from a surface by wiping with detergents. VHP and alkaline detergents
      caused degradation of doxorubicin. The observed effect with detergent cleaning
      was pH dependent, but neither of the technologies applied had any effect on the
      chemical stability of 5-flurouracil and cyclophosphamide under the conditions
      tested.

PMID- 16984749
TI  - Re-evaluation of the cost effectiveness of temozolomide for malignant gliomas in
      British Columbia.
AB  - STUDY OBJECTIVES: To re-evaluate the cost effectiveness and median overall
      survival (OS) achieved in patients with recurrent malignant gliomas treated with
      temozolomide in British Columbia, as compared to previous lomustine use in the
      same patient population based on updated outcomes data. Results were also
      compared to temozolomide literature reports. METHODS: A retrospective medical
      record review was performed to identify patients who received single agent
      temozolomide or lomustine during successive, prespecified time periods. Data were
      collected on survival, duration of therapy, drug cost, labour and supplies, and
      successive or prior chemotherapy. RESULTS: Forty-one patients in the temozolomide
      group and 25 patients in the lomustine group were analysed. The median OS was
      33.3 weeks (95% CI 28.4, 42.1 weeks) and 37.7 weeks (95% CI 25.0, 88.4 weeks)
      respectively (P = 0.783). Temozolomide patients received a mean of 5.1 cycles of
      drug treatment, with a mean cost per patient of 10746 dollars (CAD). In contrast,
      lomustine patients received a mean of 3.3 cycles of therapy, with a mean cost per
      patient of 129 dollars (CAD). The cost-effectiveness analysis showed that
      temozolomide was generally not a cost-effective strategy and that lomustine was
      the dominant strategy. In the sensitivity analysis, in scenarios where median OS
      was prolonged with temozolomide as compared to lomustine, the incremental cost
      effectiveness ratio for each life year gained ranged from 32,247 dollars to
      162,186 dollars. CONCLUSION: No difference in survival was observed between
      patients treated with single agent lomustine and temozolomide. Based on the
      higher cost and lack of additional clinical benefit of temozolomide, lomustine is
      a more cost-effective treatment strategy.

PMID- 16984750
TI  - The incidence of extravasation of vinca alkaloids supplied in syringes or mini
      bags.
AB  - STUDY OBJECTIVE: The aim of this retrospective study was to determine the
      incidence of vinca alkaloid extravasation following administration via syringes
      or mini-bags. METHODS: An electronic survey was sent to pharmacy departments at
      hospitals throughout Australia. The survey was designed to collect data on the
      administration methods of vinca alkaloids (vincristine, vinblastine, vinorelbine)
      and the corresponding documented incidence of extravasation. The questionnaire
      requested the following information: how the drugs were prepared for
      administration (syringe or mini-bag); volume of each product; number of items
      supplied; and the number of cases of extravasation reported for each product.
      RESULTS: Questionnaires were sent to 228 hospital pharmacy departments in
      Australia. Sixty-eight questionnaires were received (29.8%), including responses
      from most major cancer centres. Data represented a range of 3 to 120 months
      (mean: 38 months) of clinical experience. The reported incidence of vincristine
      extravasation from syringes was 0.03% (11/37 084) and 0.041% (3/7255) with mini
      bags. One case of vinblastine extravasation was reported with syringes 0.013%
      (1/7913), none from mini-bags (0/1421). Vinorelbine data were difficult to
      interpret as cases may represent phlebitis rather than extravasation. The
      reported incidence from vinorelbine syringes was 0.029% (2/6914) and 0.146%
      (8/5475) with mini-bags. Excluding vinorelbine data, the reported vinca alkaloid
      extravasation episodes from syringes (0.027%) and mini-bags (0.035%) were found
      to be similar and infrequent. CONCLUSION: The data suggest that vinca alkaloids
      can be given safely as low volume, short infusions via mini-bags. Policies and
      practices that ensure the same careful monitoring of infusional therapy as is
      recommended with administration by syringe may further reduce the incidence of
      untoward effects. Mini-bags should be used for the administration of vinca
      alkaloids and this practice will prevent the inadvertent intrathecal
      administration of vinca alkaloids via syringes.

PMID- 16984751
TI  - Palifermin in a hematopoietic stem cell transplant patient with osteonecrosis of
      the jaw.
AB  - This case report describes the use of palifermin in a multiple myeloma patient
      with a history of osteonecrosis of the jaw (ONJ) for the prevention of high-dose
      chemotherapy-induced mucositis. Following the day of autologous stem cell
      infusion, palifermin was discontinued secondary to adverse events. Specifically,
      palifermin-associated macroglossia seemed to exacerbate the pain localized in the
      oral cavity area affected by ONJ, necessitating escalated doses of narcotic
      analgesics. When contemplating palifermin as a mucosal protectant in a
      hematopoietic stem cell transplant patient with ONJ, a careful benefit-to-risk
      assessment is in order to ensure optimal effectiveness without undue harm.

PMID- 16984752
TI  - Letter to the editor.

PMID- 16984753
TI  - Ethics and science of stem cells: are ES cell lines outdated?

PMID- 16984754
TI  - One million and counting.
AB  - Ten years have passed since follitropin-beta first became commercially available.
      It is estimated that more than one million children have been born after ovarian
      stimulation and/or ovulation induction with this recombinant FSH in assisted
      reproduction.

PMID- 16984755
TI  - Age-matched comparison of recombinant and urinary HCG for final follicular
      maturation.
AB  - This age-matched retrospective analysis compared the clinical outcomes of
      recombinant human chorionic gonadotrophin (rHCG) and urinary HCG (uHCG) in
      patients undergoing fresh, nondonor IVF cycles. The patients underwent ovarian
      stimulation by standard gonadotrophin-releasing hormone (GnRH) agonist down
      regulation or a GnRH antagonist protocol using recombinant FSH (rFSH) alone or in
      combination with human menopausal gonadotrophin. When two or more follicles had
      attained a mean diameter of 20 mm, follicular triggering was achieved with either
      Ovidrel (rHCG) 250 mug SC or uHCG 10,000 IU IM. Patients receiving rHCG were
      considered subjects, and they were age-matched in a 1:2 ratio to patients
      receiving uHCG, who were designated as controls. The main outcome measures were
      number of oocytes retrieved, number of mature oocytes obtained, number of oocytes
      fertilized and clinical pregnancy rates. A total of 273 subjects were age-matched
      and compared with 546 controls. Recombinant HCG had a minimal effect on the
      number of oocytes retrieved (13.4 versus 13.2), mature oocytes (10.5 versus 10.3)
      and oocytes fertilized (8.2 versus 7.8) compared with uHCG. Pregnancy (46.0
      versus 45.2%) and clinical pregnancy rates (38.1 versus 36.8%) were similar for
      rHCG and uHCG. Recombinant HCG was as effective as uHCG for final follicular
      maturation in IVF cycles.

PMID- 16984757
TI  - Artificial versus stimulated cycles for endometrial preparation prior to frozen
      thawed embryo transfer.
AB  - The objective of this study was to compare the implantation rate, pregnancy rate
      and endometrial thickness of frozen-thawed embryo transfers using endometrial
      preparation with either an artificial cycle or stimulated cycle. This was a
      prospective randomized trial at a single academic IVF centre. Seventy-seven
      patients undergoing artificial cycles received oral oestradiol; patients with
      endometrium < 7 mm on day 9-10 were switched to vaginal oestradiol. Eighty-six
      patients undergoing stimulated cycles received recombinant FSH followed by human
      gonadotrophin hormone injection. Vaginal progesterone was begun 2 or 3 days prior
      to embryo transfer. There was no difference in implantation rate (8.5% versus
      7.3%), pregnancy rate (16% versus 13%), cancellation rate (both 23%) or
      endometrium thickness (8.7 +/- 1.1 mm versus 8.7 +/- 1.0 mm) between artificial
      and stimulated cycles. Stimulated cycles had a higher incidence of thin
      endometrium (27% versus 5%, P < 0.01). In artificial cycles, patients switched to
      vaginal oestradiol had improved pregnancy rate (31%) versus patients who received
      oral oestradiol alone (13%) (P = 0.05). It is concluded that artificial and
      stimulated cycles produce comparable pregnancy rates, implantation rates,
      cancellation rates and endometrial thickness, although stimulated cycles have a
      higher incidence of thin endometrium. Vaginal oestradiol supplementation improved
      implantation rates.

PMID- 16984758
TI  - Luteal hormonal profile of oocyte donors stimulated with a GnRH antagonist
      compared with natural cycles.
AB  - The effect of gonadotrophin-releasing hormone (GnRH) antagonist treatment on
      luteal phase hormonal profile has not yet been fully investigated. Cycle
      characteristics of 23 fertile donors stimulated with recombinant FSH and the GnRH
      antagonist, ganirelix 0.25, for IVF and receiving no kind of luteal
      supplementation were compared with control, natural cycles. Luteal luteinizing
      hormone (LH) serum concentrations as well area under the curve (AUC) for LH were
      significantly higher in natural cycles. In addition, luteal phase length was
      longer in natural cycles compared with donor cycles. Luteinizing hormone values
      dropped in the luteal phase of the stimulated cycles, with the lowest values
      being observed in the mid-luteal phase. AUC for progesterone in the luteal phase
      was significantly higher in the stimulated cycles compared with natural cycles (P
      < 0.001). Low LH serum concentrations and shortened luteal phase indicate the
      need for luteal phase supplementation in GnRH antagonist IVF cycles.

PMID- 16984760
TI  - The importance of diagnosis in the clinical management of infertility in the
      male.
AB  - This paper examines the importance of a clinical diagnosis in the management of
      infertility in the male and discusses the reasons for this statement. The
      treatment of male infertility is now often carried out solely by gynaecologists.
      These specialists have frequently had little training in the examination of the
      male genital tract nor have they had any teaching in either urology or in the
      pathology of the lower genito-urinary tract. The routine application of IVF may
      be a consequence of these failings and should this form of treatment be shown to
      have been unnecessary or, especially, should it result in a clinical disaster,
      then a serious medico-legal problem may result. The degree of training that is
      given to the gynaecologist working in this field is also examined and suggestions
      are made as to how this could be improved.

PMID- 16984761
TI  - Evaluation of sperm recovery following annexin V magnetic-activated cell sorting
      separation.
AB  - Magnetic-activated cell sorting (MACS) using paramagnetic annexin V-conjugated
      microbeads eliminates spermatozoa with externalized phosphatidylserine, which is
      considered one of the features of apoptosis. The objective of this study was to
      evaluate sperm recovery following the use of MACS as a sperm preparation
      technique. Mature spermatozoa were separated and divided into two fractions: the
      first was prepared by density gradient centrifugation (DGC) and MACS, while the
      second was prepared by DGC only. Following MACS, the percentage of cells
      collected in the annexin-negative fraction was significantly higher than the
      annexin-positive fraction and the sperm recovery rate was 73.8 +/- 12.1%. In
      conclusion, the integration of MACS with DGC can be considered as an effective
      sperm preparation technique that does not lead to significant cell loss.
      Separating a distinctive population of non-apoptotic spermatozoa with intact
      membranes may optimize the outcome of assisted reproduction.

PMID- 16984762
TI  - Effect of gonadotrophin priming on in-vitro maturation of oocytes collected from
      women at risk of OHSS.
AB  - This study examined the effects of human menopausal gonadotrophin (HMG) or human
      chorionic gonadotrophin (HCG) priming on cumulus-oocyte complex (COC) morphology,
      oocyte maturation and embryo development in patients undergoing in-vitro
      maturation (IVM) cycles. The patients were primed with nothing (group 1), low
      dose HMG (group 2) or 10,000 IU HCG (group 3) before oocyte retrieval. COC with
      dispersed cumulus cell appearance was only observed in group 3. In addition, 11%
      of metaphase II stage oocytes at the time of retrieval were collected from group
      3. Oocyte maturation in vitro in group 3 was faster than that in groups 1 and 2.
      The blastocyst development rate of residual embryos after embryo transfer in
      group 3 was significantly higher than that of groups 1 and 2 (P < 0.05). These
      results suggest that HCG priming may stimulate the COC, promote oocyte
      maturation, and improve developmental competence in IVM cycles.

PMID- 16984764
TI  - Impact of ovarian endometrioma on assisted reproduction outcomes.
AB  - The effects of ovarian endometrioma on fertility outcomes with IVF and embryo
      transfer have been causally related to poor outcomes. The objective of this meta
      analysis was to evaluate the ovarian reserve and ovarian responsiveness to
      ovarian stimulation and assisted reproduction outcomes in patients with ovarian
      endometrioma. The odds for clinical pregnancy were not affected significantly in
      patients with ovarian endometrioma compared with controls, with an overall odds
      ratio of 1.07 from three studies [95% CI: (0.63, 1.81), P = 0.79]. The overall
      pregnancy rate was similar with an estimated odds ratio of 1.17 [95% CI: (0.85,
      1.60), P = 0.34]. Decreased ovarian responsiveness to ovarian stimulation in
      patients with ovarian endometrioma may be due to a reduced number of follicles in
      these patients compared with controls (P = 0.002). Prospective randomized
      controlled trials are needed to assess whether surgical treatment versus no
      surgical treatment improves pregnancy outcomes in patients with ovarian
      endometrioma undergoing assisted reproduction cycles.

PMID- 16984766
TI  - Inhibition of human spermatozoa-zona pellucida binding by a combinatorially
      derived peptide from a synthetic target.
AB  - Intact zona-free human oocytes were screened using a combinatorial peptide
      library selection protocol. Pieczenik Peptide Sequence 1 (PPS1) HEHRKRG binds
      human spermatozoa. A complementary and unique binding sequence HNSSLSPLATPA
      (PPS2) was developed from the first PPS1 ligand that binds to the human zona
      pellucida or oolemma. Cytoplasm-free zonae from unfertilized eggs were obtained
      and used as an assay system to test the effects of exposure to these two ligands.
      Spermatozoa were inserted into evacuated zonae and their behaviour and binding
      activity were assessed at regular intervals. The behaviour of spermatozoa exposed
      to PPS1 and unlabelled spermatozoa injected into unexposed zonae was similar as
      far as binding was concerned (50 and 54% binding), but PPS1 exposed spermatozoa
      had higher motility and displacement, marked by their escape from the zona
      pellucida. Zonae exposed to PPS2 inhibited the interaction between injected
      spermatozoa and the inside of the zona when compared with controls (8.3 and 53.8%
      attached respectively, P < 0.001). The sperm-zona pellucida interaction described
      in this paper is applied as a functional assay for molecular interactions of
      sperm binding and can be used to assess function for potential surface markers on
      gametes. It is shown here that a unique binding ligand (PPS2) can be synthesized
      from another complimentary ligand (PPS1) without the need for a known
      intermediate substrate. PPS1 and PPS2 may have properties that can be used to
      target processes involved in conception and assisted reproduction. A movie
      sequence taken approximately 30 min after injection of spermatozoa into empty
      human zonae pellucidae shows behaviour of non-manipulated spermatozoa into zonae
      not exposed or exposed to ligand. This may be purchased for viewing on the
      Internet at www.rbmonline.com/Article/2159 (free to web subscribers).

PMID- 16984767
TI  - Contribution of embryo cryopreservation to elective single embryo transfer in IVF
      ICSI.
AB  - Single embryo transfer is the best way to reduce the risk of multiple pregnancy
      in IVF-intracytoplasmic sperm injection (ICSI). Between June 2002 and December
      2004, all patients (first cycle, female age <38 years) were offered the choice
      between having one (SET) or two (DET) embryos transferred. Among 493 couples, 428
      had at least two good quality embryos, and among them, 32% opted for SET. The SET
      and DET populations were not comparable (patients in the SET group were younger
      and had more oocytes retrieved), and therefore a paired, case-control analysis
      was performed involving 130 SET couples and 130 DET couples, matched according to
      the female partners' ages and the numbers of embryos available. All of the SET
      patients, and 82% of the DET group, had at least one embryo cryopreserved, (3.9
      versus 2.8 embryos). The option of SET was continued for the frozen-thawed embryo
      transfers. The pregnancy rate following embryo transfer was significantly lower
      after SET compared with DET for both fresh (27.6 versus 36.9%; P < 0.05) and
      frozen-thawed (14.4 versus 23.5%) embryos. However, the cumulative live birth
      rates following the transfer of fresh and frozen embryos were identical between
      the two groups (43 versus 45%), with a high prevalence of twins following DET (34
      versus 0%).

PMID- 16984768
TI  - Sequential transfer of day 3 embryos and blastocysts after previous IVF failures
      despite adequate ovarian response.
AB  - The purpose of this study was to compare IVF outcome following sequential embryo
      transfer (ET) with that following the transfer of early cleavage embryos among
      patients with previous multiple IVF failures but adequate ovarian response. A
      retrospective matched case-control analysis was made of the medical files of 66
      women who underwent sequential transfer of day 3 embryos and blastocysts in the
      Chaim Sheba Medical Centre between January 1999 and May 2004. The control group
      included 117 matched women who underwent embryo transfer on day 3 only.
      Sequential transfer of embryos in women resulted in a pregnancy rate of 30.3%
      (20/66) compared with 17.1% (20/117) following day 3 ET (P < 0.05). Multiple
      pregnancies (most of them twins) were significantly more common in women
      undergoing sequential transfer (10/20 versus 2/20; P < 0.02). Sequential transfer
      of embryos may be indicated for women with repeated IVF cycles, but the number of
      embryos transferred must be limited in order to prevent multifetal gestations.
      More data are needed to support this approach.

PMID- 16984770
TI  - Observations on intrauterine oxygen tension measured by fibre-optic microsensors.
AB  - Understanding the biology of reproductive organs is essential for the development
      of assisted reproductive techniques. There is at present no direct evidence for
      either the concentration and dynamics of intrauterine oxygen tension at the
      endometrial surface, nor its importance for the receptiveness of the endometrium.
      In this study a new method measured mid-cycle (ranging from day 12-18)
      endometrial surface oxygen tension in 21 patients referred to intrauterine
      insemination (IUI). Time series was measured online for a period of 5-10 min. The
      (mean) individual oxygen tension among patients varied from 4 to 27% air
      saturation. Overall mean oxygen tension among all patients was 11.8% air
      saturation. Within the same patient, considerable time-related variations were
      observed. Some patients exhibited rhythmic oscillations with a frequency in the
      order of 1 min, whereas others did not show any regular patterns. A good
      description of endometrial surface oxygen concentration and dynamics was thus
      obtained, but given the relatively small number of participants, an association
      with pregnancy following insemination could not be established. Further studies
      using this new method could elucidate the association between individual
      intrauterine activity, embryo implantation and endometrial surface oxygen
      tension.

PMID- 16984771
TI  - Prevention of multiple pregnancies after IVF in women 38 and older: a randomized
      study.
AB  - The objective of this study was to answer the question of whether a double
      instead of triple embryo transfer strategy in patients over 38 years would
      substantially reduce the number of multiple pregnancies while maintaining the
      chance of a term live birth at an acceptable level. A randomized controlled two
      centre trial was performed. Forty-five patients, 38 years or older, were
      randomized. Double embryo transfer over a maximum of four cycles (DET group) or
      triple embryo transfer over a maximum of three cycles (TET group) was performed.
      The cumulative term live birth rate was 47.3% after four cycles in the DET group
      and 40.5% after three cycles in the TET group. The difference between the DET and
      the TET group was 6.8% in favour of the DET group (95% CI -25 to 38). The
      multiple pregnancy rates in the DET and TET group were 0% (95% CI 0 to 24) and
      30% (95% CI 7 to 65) respectively (P = 0.05). In the DET patients, the mean
      number of treatment cycles was 2.9 compared with 2.1 in the TET group (P = 0.01).
      In women of 38 years and older, double embryo transfer after IVF may result in
      similar cumulative term live birth rates compared with triple embryo transfer,
      provided that a higher number of treatment cycles is accepted.

PMID- 16984773
TI  - Use of Chuk as an internal standard suitable for quantitative RT-PCR in mouse
      preimplantation embryos.
AB  - Analysis of gene expression changes during preimplantation development by
      quantitative reverse transcription-polymerase chain reaction (Q-PCR) requires
      appropriate internal standards. Ideally, such a gene should show a constant level
      of transcripts per embryo across all preimplantation stages from unfertilized
      eggs to blastocysts. By analysing the microarray-based gene expression profiles
      of preimplantation embryos, it was found that a conserved helix-loop-helix
      ubiquitous kinase gene (Chuk, also known as IkappaB kinase alpha, IKKalpha or
      IKK1) satisfied this criterion. To test the utility of this gene as an internal
      standard for Q-PCR, the expression levels of two known genes (Nalp5/Mater,
      Pou5f1/Oct3/Oct4) were normalized by Chuk and other housekeeping genes (Actb,
      Gapdh, Eef1a1, and H2afz) and demonstrated that the former was more consistent
      with the expression patterns obtained by a whole-mount in-situ hybridization than
      those reported previously with the latter. It is concluded that Chuk, unlike
      other commonly used normalization controls, is a reliable and suitable internal
      standard for measuring gene expression levels by Q-PCR in mouse oocytes and
      preimplantation embryos.

PMID- 16984774
TI  - Can Vero cell co-culture improve in-vitro maturation of bovine oocytes?
AB  - This study was carried out to evaluate the effect of Vero cell co-culture on
      developmental competence of immature oocytes. Bovine cumulus-oocyte complexes
      (COC) were matured in presence or absence of Vero cells. Matured oocytes were
      inseminated and cultured for up to 9 days. Cleavage percentages were recorded on
      day 2 after insemination and embryos were evaluated on a daily basis.
      Expanding/expanded and hatching/hatched blastocysts were used for cell number
      assay. Results indicated a significantly greater cleavage percentage in oocytes
      matured in presence of Vero cells than control (86% versus 76%, P < or = 0.05).
      The percentages of advanced embryos appear to be greater on a daily basis in COC
      matured in presence of Vero cells compared with control. However, these
      differences were not significant. Blastocysts derived from COC matured in the
      presence of Vero cells had a significantly higher (P < or = 0.05) number of inner
      cell mass, trophectoderm and total cell number in expanding/expanded (65.25,
      224.5 and 289.7 respectively) and hatching/hatched (67.75, 289.75 and 357.5)
      embryos in comparison to the control (42, 203.5, 245.5 and 51.3, 265, 316.3
      respectively). Results confirm that co-culture of bovine COC during in-vitro
      maturation, enhances their ability for cleavage and for producing blastocysts
      with higher quality.

PMID- 16984776
TI  - Feeder layer- and serum-free culture of rhesus monkey embryonic stem cells.
AB  - The common culture system of rhesus monkey embryonic stem (rES) cells depends
      largely on feeder cells and serum, which limits the research and application of
      rES cells. This study reports a feeder layer-free and serum-free system for
      culture of rES cells. rES cells could be cultured through at least 22 passages on
      laminin in medium supplemented with serum replacement (SR), basic fibroblast
      growth factor (bFGF) and transforming growth factor beta1 (TGFbeta1), and
      maintained stable proliferation rates and normal karyotypes, while displaying all
      the embryonic stem cell characteristics including morphology, alkaline
      phosphatase (AKP), Oct-4, cell surface markers SSEA-3, SSEA-4, TRA-1-60 and TRA-1
      81, and formed cystic embryoid bodies in vitro. In addition, the studies showed
      that TGFbeta1, bFGF and laminin are necessary for maintaining the
      undifferentiated growth of rES cells in long-term culture. Moreover, withdrawal
      of TGFbeta1 increased the differentiation rate by decreasing the expression of
      integrins. Therefore, this system would provide a well-defined culture system for
      rES cells, and would facilitate research into self-renewal and differentiation
      mechanisms of rES cells.

PMID- 16984777
TI  - Cryopreservation of murine embryos, human spermatozoa and embryonic stem cells
      using a liquid nitrogen-free, controlled rate freezer.
AB  - A Stirling Cycle Cryocooler has been developed as an alternative to conventional
      liquid nitrogen controlled rate freezers. Unlike liquid nitrogen systems, the
      Stirling Cycle freezer does not pose a contamination risk, can be used in sterile
      conditions and has no need for a constant supply of cryogen. Three types of
      samples from two species (murine embryos, human spermatozoa and embryonic stem
      cells), each requiring different cooling protocols, were cryopreserved in the
      Stirling Cycle freezer. For comparison, cells were also frozen in a conventional
      liquid nitrogen controlled rate freezer. Upon thawing, the rates of survival of
      viable cells were generally greater than 50% for mouse embryos and human
      embryonic stem cells, based on morphology (mouse embryos) and staining and colony
      formation (human embryonic stem cells). Survival rates of human spermatozoa
      frozen in the Stirling Cycle freezer, based on motility and dead cell staining,
      were similar to those of samples frozen in a conventional controlled rate freezer
      using liquid nitrogen.

PMID- 16984778
TI  - Human oocyte cryopreservation: past, present and future.
AB  - Despite inferior results in the past compared with embryo freezing, oocyte
      cryopreservation has made great strides in recent years. In fact, it has become a
      necessity in assisted reproduction technology, providing alternatives to legal,
      moral and religious problems originating from embryo freezing. Recent advances in
      freezing technology, modifications of conventional protocols used and continuing
      optimization of vitrification have efficiently improved the method. A historical
      description of the method's progression over time, and a comparison of
      principles, procedures and results as reported in the literature are presented in
      this review.

PMID- 16984779
TI  - In-vitro maturation of oocytes: biological aspects.
AB  - Natural cycle and in-vitro maturation (IVM) of oocytes are becoming interesting
      alternatives to classical assisted reproduction technology approaches for
      patients, especially in those at high risk for ovarian hyperstimulation syndrome
      or with poor ovarian reserve. More than for their clinical and biological
      indications, natural cycle and IVM of oocytes can also be considered as good
      social and economic alternatives to the classical IVF treatment, based on their
      financial cost-effectiveness with exclusion of expensive medications. To be
      successful, IVM must entail both nuclear and cytoplasmic maturation, and its
      maturation and success rates are affected by the number of collected cumulus
      layers, the degree of atresia and the maturation rate between 24 and 48 h.
      Endogenous regulation of oocyte maturation is a complex sequence of events
      regulated by endocrine parameters, oocyte/follicular cross-talk, and intra-oocyte
      kinase/phosphatase interactions. This complex process requires a better
      definition of each contributing factor affecting oocyte development and the
      resulting embryo quality. The clinical aspects of IVM have been documented
      earlier; the present paper will mainly focus on the biological aspect of oocyte
      maturation in vitro and the quality of derived embryos.

PMID- 16984780
TI  - The role of patients' associations in assisted reproduction treatment.

PMID- 16984782
TI  - Behavioural reactivation and subjective assessment of the state of vigilance-
      application to simulated car driving.
AB  - The frequency of some behaviour (such as self-centred gestures) increases during
      a task that leads to the occurrence of low-vigilance episodes. These gestures can
      be useful in stimulating oneself. A study carried out in 20 adults has enabled us
      to state that motor activity (recorded with an actimeter) increases with the
      duration of a monotonous driving task and sleep deprivation. The analysis of the
      scores recorded using the Karolinska Sleepiness Scale has shown that drivers can
      assess the deterioration of their state of vigilance according to the actual
      sleep preceding the driving test. Finally, the joint analysis of the subjective
      and objective data revealed a co-variation of these two types of indices. We
      discuss the stimulatory function of the motor activity in a task leading to the
      occurrence of low-vigilance episodes by investigating, among other things, the
      use, conscious or not, of this type of activity.

PMID- 16984783
TI  - Analysis of total work inability in Poland in 2000 and 2001 according to age,
      disease diagnosis and occupation.
AB  - This study was to determine the main health-related reasons, age and occupation
      of those who took early retirement. This was done through an analysis of the data
      from Poland's Social Insurance Institution (ZUS) from 2000 and 2001. An analysis
      of these data showed an increase in the number of certificates confirming total
      inability to work in people over 40 years old. Over 50% of certificates work were
      issued to workers in 2 age-groups: 45-49 and 50-54. Diseases of the circulatory
      system, musculoskeletal system and connective tissue as well as mental and
      behavioural disorders are the main causes of early inability to work.
      Approximately 70% of people who obtained certificates confirming total inability
      to work had blue- and blue-and-white-collar jobs.

PMID- 16984784
TI  - Effects of diabetic neuropathy on body sway and slip perturbation detection in
      older population.
AB  - Postural control is a common mechanism to compensate for unexpected displacements
      of the body. In the older population, a slip or fall due to a failure of postural
      control is a common cause of morbidity and mortality. The ability of postural
      control decreases with aging or neuropathy. In this study, 2 groups, diabetics
      and non-diabetics in the older population, were compared to determine how
      patterns of postural sway during quiet standing were related to the detection of
      perturbation. The SLIP-FALLS system was applied to the measurement of sway and
      detection of perturbation. In phase 1 of the development of the predictive model,
      neural network algorithms were applied to find determinant variables for
      perturbation detection. In phase 2, a fuzzy logic inference system was developed
      to investigate the relationship between sway and perturbation detection. Results
      of this study may be applied to the design of floor mats or shoe insoles for
      preventing fatigue in workplaces.

PMID- 16984785
TI  - Recent trends in ILO conventions related to occupational safety and health.
AB  - The present study was conducted to analyze the ratification status of
      International Labour Organization (ILO) conventions related to occupational
      safety and health (OSH) by ILO member states in terms of national indicators
      (length of ILO membership and national income status) and regional affiliation.
      17 conventions designated as OSH-related by the 2003 International Labour
      Conference were examined. In general, countries with longer ILO membership
      ratified higher numbers of conventions related to OSH. With some variation, long
      membership countries had the largest number of ratifications, followed by middle-
      and short-membership countries in all regions. There were also incremental
      increases in the number of ratifications for OSH-related conventions according to
      the national income status. Common regional characteristics that could not be
      explained by the factors studied also existed. Future efforts to increase
      ratification at an international level will need to consider the factors
      influencing ratification practice among the member states.

PMID- 16984786
TI  - The effect of job and environmental factors on job satisfaction in automotive
      industries.
AB  - A methodology was developed for diagnosing industrial work, which includes
      questionnaire, observation, measurements, data collection and statistical
      analysis. A survey was conducted to investigate the relationship between job
      satisfaction and factors that affect work design in 2 automotives manufacturing
      companies in Malaysia. A basic work design model was proposed. The aim of this
      model was to determine the factors that influence employees' perception towards
      their work. A set of multiple-choice questionnaires was developed and data was
      collected by interviewing employees at a production plant. The survey focused on
      job and environmental factors. The results supported the proposed model and
      showed that job and environmental factors were significantly related to job
      satisfaction. They highlighted the significant influence of age, work experience
      and marital status on job satisfaction. Further, environmental factors,
      especially the surroundings, context dependence and the building's function, also
      had a significant impact on job satisfaction.

PMID- 16984787
TI  - Driver celeration behavior and the prediction of traffic accidents.
AB  - A study was undertaken to investigate whether driver celeration (overall mean
      speed change) behavior can predict traffic accident involvement. Also, to test
      whether acceleration, deceleration or the combined celeration measure was the
      better predictor. Bus driver celeration behavior was measured repeatedly in real
      traffic, driving en route, and correlated with accidents for which the drivers
      were deemed at least partly responsible. Correlations around .20 were found in
      several samples between celeration behavior and culpable accidents for a 2-year
      period. The results show that although celeration behavior is only semi-stable
      over time, it predicts with some accuracy individual accident involvement over 2
      years. The predictive power of acceleration and deceleration was slightly lower
      than the combined measure, in accordance with theory. The correlations found were
      strong enough to warrant the use of celeration behavior as a predictive variable
      for transportation companies in their safety work.

PMID- 16984788
TI  - Test of firefighter's turnout gear in hot and humid air exposure.
AB  - Five students of a rescue training school cycled at 50 W for 20 min at 20 degrees
      C before walking at 5 km/hr up to 30 min in a climatic chamber at 55 degrees C
      and 30% relative humidity. 4 different types of clothing ensembles differing in
      terms of thickness and thermal insulation value were tested on separate days. All
      subjects completed 28-30 min in light clothing, but quit after 20-27 min in 3
      firefighter ensembles due to a rectal temperature of 39.0 degrees C or subjective
      fatigue. No difference in the evolution of mean skin or rectal temperature was
      seen for the 3 turnout ensembles. Sweat production amounted to about 1000 g in
      the turnout gears of which less than 20% evaporated. It was concluded that the
      small differences between the turnout gears in terms of design, thickness and
      insulation value had no effect on the resulting heat physiological strain for the
      given experimental conditions.

PMID- 16984789
TI  - The influence of anchor devices on the performance of retractable type fall
      arresters protecting against falls from a height.
AB  - Retractable type fall arresters are part of the equipment used for protecting
      people against falls from a height. They are an intermediate part between full
      body harness worn by a man and the structural anchor at the worksite. The most
      important task of retractable type fall arresters is to arrest people's falls and
      to reduce their harmful consequences. Information received from users as well as
      laboratories testing protective equipment indicates that the performance of such
      equipment is incorrect under specific conditions. The paper is concerned with an
      analysis of the conditions in which retractable type fall arresters demonstrate
      intermittent performance and with an explanation of that phenomenon. The results
      of tests investigating anchor devices and the performance of retractable type
      fall arresters are presented. External and internal factors contributing to
      intermittent performance have been determined and guidelines for safer use of
      these devices have been developed.

PMID- 16984790
TI  - Computer professionals and Carpal Tunnel Syndrome (CTS).
AB  - Carpal Tunnel Syndrome (CTS) is an important problem among computer
      professionals. Hence the prevalence of CTS among computer professionals and risk
      factors were studied. 648 subjects were selected from 4,276 computer
      professionals from 21 companies by with simple random sampling method. CTS was
      diagnosed based on clinical features. The prevalence of CTS was found to be 13.1%
      (95% CI 10.5-15.7%). Subjects with over 8 years of computer work, over 12 hrs of
      work per day and system administrators were at a higher risk for CTS (OR 3.3, 4.9
      and 2.5 respectively). Flexed or extended hand position had higher risk for CTS.
      Higher risk for CTS was found with higher exposure to computer work. Ergonomic
      considerations are important in facilitating proper positioning of hand while
      working with a computer. Further studies on CTS risk factors among computer
      professionals are essential for planning prevention.

PMID- 16984791
TI  - Attributes of occupational injury among workers in the chemical industry and
      safety issues.
AB  - Case-study research was carried out with a view to find the attributes of
      occupational injury among workers in the chemical industry and to enhance safety
      issues. Injury data were collected and processed in terms of different variables,
      such as age, gender, skills, type of hazard, etc. Pareto analysis was then
      applied to find a pattern of occupational injury among the workers. The study
      revealed that 79.52% of the injured workers were in the 40-59 age group; 57.14%
      of accidents occurred during the 1st shift; 73.26% of accidents caused injury to
      hands, feet, chest to thigh, arms and eyes; and 70.93% of injuries were caused by
      pumps, carrying and lifting, vehicles, pipelines, valves, and grinding.
      Surprisingly, no one was injured in the group of temporary workers. The paper
      also provides specific suggestions followed by some action plans.

PMID- 16984793
TI  - NIH awards 13.3 million dollars to Found National Technology Center for Networks
      and Pathways.

PMID- 16984794
TI  - Reengineering the clinical research enterprise: will the new vision for
      translational and clinical science be successful without more support for
      mentors?

PMID- 16984795
TI  - Achieving personalized cancer medicine: trials and tribulations.

PMID- 16984796
TI  - Intradermal capsaicin causes dose-dependent pain, allodynia, and hyperalgesia in
      humans.
AB  - BACKGROUND: Intradermal capsaicin is a human pain model that produces reliable
      pain and sensitization. This model facilitates controlled testing of analgesic
      efficacy via a crossover design while minimizing confounding variables in
      clinical pain states and retaining sufficient power with small samples. METHODS:
      To determine the lowest dose of capsaicin that produces consistent neurosensory
      measures, we administered 0.1, 1, 10, or 100 microg to healthy volunteers in a
      blinded manner (N = 19). Pain scores were recorded at 0, 5, 10, 15, and 60
      minutes on a visual analog scale from 0 to 100. Areas and intensities of
      mechanical allodynia (foam brush stimulus) and pinprick hyperalgesia (von Frey
      test) were quantified at 15 and 60 minutes, as were flare areas. RESULTS:
      Capsaicin produced dose-dependent increases in spontaneous pain (p = .013), the
      area and intensity of mechanical allodynia (p = .006 and p < .001, respectively),
      the area and intensity of pinprick hyperalgesia (p = .010 and p = .014,
      respectively), and the flare area (p = .010). The 10 microg dose produced greater
      spontaneous pain than the 1 microg dose (p = .017). The 100 microg dose produced
      greater spontaneous pain than the 10 microg, but the difference was not
      statistically significant. CONCLUSION: The 10 and 100 microg capsaicin doses
      produced robust pain measures across a range of modalities, and lower doses
      produced minimal effects. Whereas most studies use 100 microg, using a lower dose
      is reasonable and may facilitate detection of subtle analgesic effects-
      particularly with nonopioid analgesics--and drugs can be tested in lower doses,
      minimizing adverse side effects.

PMID- 16984797
TI  - Effects of antenatal betamethasone on maternal and fetoplacental matrix
      metalloproteinases 2 and 9 activities in human singleton pregnancies.
AB  - BACKGROUND: A single course of antenatal betamethasone is administered to women
      at risk of preterm labor to advance fetal lung maturation. Matrix
      metalloproteinases (MMPs) are collagen-degrading enzymes that remodel
      extracellular matrix components during lung development. We tested the hypothesis
      that the effects of betamethasone on fetal lung maturation involve changes in MMP
      activity. METHODS: We conducted a prospective, observational pilot study of three
      groups of singleton pregnancies. Group 1 (n = 21) was composed of women who were
      antenatally treated with a single course of betamethasone and who delivered < 37
      weeks of gestation, group 2 (n = 7) was composed of matched untreated women who
      delivered < 37 weeks of gestation, and group 3 (n = 15) was composed of untreated
      women who delivered > 37 weeks of gestation. Maternal blood, mixed cord blood,
      and placental samples were collected at the time of delivery for MMP-2 and MMP-9
      activity and tissue inhibitor of metalloproteinases (TIMP)-1 and -2 levels.
      RESULTS: MMP-2 activity was significantly higher in the maternal, placental, and
      fetal compartments in group 1 compared with group 2 (p < .05). TIMP-2 levels were
      lower in groups 1 and 2 compared with group 3. Maternal TIMP-2 levels were higher
      (p < 0.003), whereas fetal TIMP-1 (p < .01) and MMP-9 to TIMP-1 ratios (p < .05)
      were lower when delivery was delayed more than 2 weeks following betamethasone
      treatment. CONCLUSION: We conclude that elevated MMP-2 activity in the maternal
      and fetoplacental compartments may suggest a mechanism, in part, for
      betamethasone-induced fetal lung maturation.

PMID- 16984798
TI  - Diagnosis and treatment of peripheral arterial disease compared with other
      atherosclerotic vascular diseases in a university primary care clinic.
AB  - BACKGROUND: Despite the fact that peripheral arterial disease (PAD) significantly
      increases the risk of cardiovascular mortality, it is significantly
      underdiagnosed and undertreated. The purpose of this study was to evaluate the
      practice at a northeast Tennessee university primary care clinic regarding the
      diagnosis and treatment of PAD. METHODS: A retrospective medical record survey
      was conducted to evaluate practice patterns in diagnosing and treating PAD in a
      university primary care clinic. A clinic population of 711 patients was selected
      using International Classification of Diseases-9 codes for coronary artery
      disease (CAD), cerebovascular disease (CVD), and/or PAD. A sample of 180 patients
      (25.3%) was randomly selected using a systematic statistical method. Of these,
      125 patients met the diagnostic criteria for CAD, CVD, and/or PAD. The study
      covered a 3-year period, from July 2001 until June 2004. Demographic and other
      data, including the use of antiplatelet therapy, were collected. RESULTS: One
      hundred ten patients met all of the inclusion and exclusion criteria. Thirty-nine
      percent were males, and 61% were females. Overall, 79% had CAD, 53% had CVD, and
      25% had PAD. Almost half of the patients had some combination of these. Only
      about 2% had PAD only compared with 36% with CAD only and 17% with CVD only.
      Although the prevalence of CAD and CVD (among other atherosclerotic vascular
      diseases) in our clinic was comparable to national figures, the prevalence of PAD
      was significantly lower (p = .004). The overall use of any antiplatelet agent was
      84.2% for patients with only CAD and 80% for only CVD. There was not an adequate
      number of patients with only PAD to evaluate the use of antiplatelet therapy in
      this group. CONCLUSION: The low prevalence of PAD only (most PAD patients had
      coexisting CAD and CVD) indicates that PAD is underdiagnosed at our clinic. There
      was suboptimal use of aspirin and other antiplatelet drugs among patients with
      atherosclerotic vascular disease.

PMID- 16984799
TI  - Proinflammatory reaction and cytoskeletal alterations in endothelial cells after
      shock wave exposure.
AB  - BACKGROUND: Although the effects on human organs by shock waves (SWs) induced by
      medical treatments or high-energy trauma are well recognized, little is known
      about the effects on the cellular level. Since blood vessel injury is a common
      finding after SW exposure, we assessed the in vitro effects of SWs on human
      umbilical vein endothelial cells (HUVECs). METHODS: An in vitro trauma model was
      used to expose HUVEC monolayers to focused SWs or to shock waves plus cavitation
      (SWC), a subsequent phenomenon that is often considered the main cause of SW
      vascular injury. RESULTS: SWs alone did not cause any changes in the studied
      variables. In contrast, HUVEC monolayers exposed to SWC exhibited discrete
      central lesions with extensive cell death. Cells peripheral to the main lesion
      area displayed disassembly of dense peripheral bands and formation of actin
      stress fibers, indicating increased intercellular gaps. Expression of P-selectin
      was enhanced 11-fold compared with controls, whereas expression of E-selectin and
      intercellular adhesion molecule 1 was enhanced 8-fold (p < .05) and 1.5-fold (p <
      .01), respectively. The latter responses were preceded by nuclear translocation
      of nuclear factor kappaB subunit p65 by 16% (p < .01). When compared with
      mechanically produced lesions used as controls, SWC lesions exhibited an impaired
      regeneration rate of the endothelial cell layer (p < .001). Redistribution of
      centrosomes toward the lesion borders was less effective in the SWC samples
      compared with the mechanically produced lesions (p < .01). CONCLUSIONS: SWC
      lesions were associated with a switch to an endothelial proinflammatory
      phenotype, with an impaired regeneration rate and changes in cytoskeletal
      functions.

PMID- 16984800
TI  - Inhibition of NF-kappa B activation through targeting I kappa B kinase by
      celastrol, a quinone methide triterpenoid.
AB  - Celastrol, a quinone methide triterpenoid, was isolated as an inhibitor of NF
      kappaB from Celastrus orbiculatus. This compound dose-dependently inhibited a
      variety of stimuli-induced NF-kappa B-regulated gene expression and the DNA
      binding of NF-kappa B in different cell lines without affecting DNA-binding
      activity of AP-1. Preincubation of celastrol completely blocked the LPS-, TNF
      alpha-, or PMA-induced degradation and phosphorylation of I kappa B alpha.
      Importantly, celastrol inhibited IKK activity and the constitutively active IKK
      beta activity in a dose-dependent manner without either affecting the NF-kappa B
      activation induced by RelA over-expression or directly suppressing the DNA
      binding of activated NF-kappa B. However, mutation of cysteine 179 in the
      activation loop of IKK beta abolished sensitivity towards to celastrol,
      suggesting that celastrol suppressed the NF-kappa B activation by targeting
      cysteine 179 in the IKK. To verify that celastrol is a NF-kappa B inhibitor, we
      investigated its effect on some NF-kappa B target genes expressions. Celastrol
      prevented not only LPS-induced mRNA expression of iNOS and TNF-alpha, but also
      TNF-alpha-induced Bfl-1/A1 expression, a prosurvival Bcl-2 homologue. Consistent
      with these results, celastrol significantly suppressed the production of NO and
      TNF-alpha in LPS-stimulated RAW264.7 cells, and increased the cytotoxicity of TNF
      alpha in HT-1080 cells. We also demonstrated that celastrol showed anti
      inflammatory and anti-tumor activities in animal models. Taken together, this
      study extends our understanding on the molecular mechanisms underlying the anti
      inflammatory and anti-cancer activities of celastrol and celastrol-containing
      medicinal plant, which would be a valuable candidate for the intervention of NF
      kappa B-dependent pathological conditions.

PMID- 16984801
TI  - Traumatic dislocation of the lumbosacral junction diagnosis, anatomical
      classification and surgical strategy.
AB  - PURPOSE OF THE STUDY: Traumatic lumbosacral dislocation is a rare lesion often
      characterised by a fracture dislocation of L5-S1 articular facets associated with
      anterior L5 slipping. Because of its rarity, the surgical strategy of lumbosacral
      traumatic dislocation remains controversial. We report the most important series
      of traumatic lumbosacral dislocation. The cases of six men and five women are
      presented. We discuss the diagnosis and surgical treatment options regarding the
      different type of lesions. A moderate anterior slipping of L5 over S1 was present
      in eight cases. The lesion was a bilateral lumbosacral fracture dislocation in
      eight cases, a pure lateral dislocation in two cases and a unilateral rotatory
      dislocation in one case. Patients were multiple-trauma patients in eight cases. A
      radicular deficit was present in two cases. All patients were treated surgically
      with a posterior osteosynthesis and fusion. A circumferential fusion was made in
      six cases. In four cases, the anterior fusion was made during the posterior
      approach. The postoperative course was favorable in all the cases. One patient
      necessitated secondarily an iterative posterior lumbosacral fixation and anterior
      fibular bone graft because of a lumbosacral pseudarthrosis. Traumatic dislocation
      of the lumbosacral junction is a rare and severe spinal fracture which occurs in
      patients after high energy trauma and could be initially misdiagnosed. We devised
      a new classification based on anatomical lesions. Treatment is always surgical,
      requiring reduction, osteosynthesis, and fusion. In case of L5 anterior slipping,
      it is crucial to assess the L5S1 disc by MRI or surgical exploration for disc
      disruption. In such case, we recommend to perform circumferential fusion to
      prevent lumbosacral pseudarthrodesis.

PMID- 16984803
TI  - On parameter estimation in population models.
AB  - We describe methods for estimating the parameters of Markovian population
      processes in continuous time, thus increasing their utility in modelling real
      biological systems. A general approach, applicable to any finite-state continuous
      time Markovian model, is presented, and this is specialised to a computationally
      more efficient method applicable to a class of models called density-dependent
      Markov population processes. We illustrate the versatility of both approaches by
      estimating the parameters of the stochastic SIS logistic model from simulated
      data. This model is also fitted to data from a population of Bay checkerspot
      butterfly (Euphydryas editha bayensis), allowing us to assess the viability of
      this population.

PMID- 16984802
TI  - Cholinergic-receptor-independent dysfunction of mitochondrial respiratory chain
      enzymes, reduced mitochondrial transmembrane potential and ATP depletion underlie
      necrotic cell death induced by the organophosphate poison mevinphos.
AB  - Our current understanding of the nature of cell death that is associated with
      fatal organophosphate poisoning and the underlying cellular mechanisms is
      surprisingly limited. Taking advantage of the absence in an in vitro system of
      acetylcholinesterase, the pharmacological target of organophosphate compounds,
      the present study evaluated the hypothesis that the repertoire of cholinergic
      receptor-independent cellular events that underlie fatal organophosphate
      poisoning entails induction of mitochondrial dysfunction, followed by
      bioenergetic failure that leads to necrotic cell death because of ATP depletion.
      Pheochromocytoma PC12 cells incubated with the organophosphate pesticide
      mevinphos (0.4 or 4mumol) for 1 or 3h underwent a dose-related and time-dependent
      loss of cell viability that was not reversed by muscarinic (atropine) or
      nicotinic (mecamylamine) blockade. This was accompanied by depressed NADH
      cytochrome c reductase, succinate cytochrome c reductase or cytochrome c oxidase
      activity in the mitochondrial respiratory chain, reduced mitochondrial
      transmembrane potential, decreased ATP concentration, elevated ADP/ATP ratio,
      increased lactate dehydrogenase release and necrotic cell death. We conclude that
      Mev induces cholinergic receptor-independent necrotic cell death by depressing
      the activity of Complexes I to IV in the mitochondrial respiratory chain,
      eliciting reduction in mitochondrial transmembrane potential, depleting
      intracellular ATP contents and damaging cell membrane integrity.

PMID- 16984804
TI  - L-Asparaginase from Erwinia Chrysanthemi 3937: cloning, expression and
      characterization.
AB  - Bacterial L-asparaginases (L-ASNases) catalyze the conversion of L-asparagine to
      L-aspartate and ammonia. In the present work, we report the cloning and
      expression of L-asparaginase from Erwinia chrysanthemi 3937 (ErL-ASNase) in
      Escherichia coli BL21(DE3)pLysS. The enzyme was purified to homogeneity in a
      single-step procedure involving cation exchange chromatography on an S-Sepharose
      FF column. The enzymatic and structural properties of the recombinant enzyme were
      investigated and the kinetic parameters (K(m), k(cat)) for a number of substrates
      were determined. In addition, we found that the enzyme can be efficiently
      immobilized on epoxy-activated Sepharose CL-6B. The immobilized enzyme retains
      most of its activity (60%) and shows high stability at 4 degrees C. The approach
      offers the possibility of designing an ErL-ASNase bioreactor that can be operated
      over a long period of time with high efficiency, which can be used in leukaemia
      therapy.

PMID- 16984805
TI  - MRSA in non-clinical areas of hospitals.

PMID- 16984806
TI  - Prevention of catheter-related bloodstream infections: analysis of studies
      published between 2002 and 2005.
AB  - As the most recent guidelines for the prevention of catheter-related bloodstream
      infections (CR-BSIs) were published four years ago, a systematic review was
      conducted to determine whether any recently published articles should further
      influence existing guidelines. Articles published between 2002 and 2005 dealing
      with infection control measures for prevention of CR-BSI were evaluated in order
      to identify evidence for the possible modification of routine practice. Special
      emphasis was placed on randomized controlled trials (RCTs), meta-analyses or
      systematic reviews, and studies applying multi-module interventions. Thirty-three
      RCTs and 10 meta-analyses or systematic reviews were retrieved. In addition, 10
      cohort studies were identified where multi-module programmes were introduced for
      reducing CR-BSI rates. It was found that RCTs and meta-analyses only have a minor
      influence on the existing guidelines for the prevention of CR-BSIs and confirm
      the earlier recommendations on several points. Studies investigating multi-module
      programmes, however, found a substantial reduction in CR-BSIs ranging from 29% to
      95%. The data show that many CR-BSIs are preventable and that there is room for
      improvement in many institutions. Simple interventions are often useful for
      reducing CR-BSI rates and the opportunities to decrease CR-BSI rates appear to be
      greatest when multi-module programmes are applied. An average reduction of more
      than 50% seems to be possible.

PMID- 16984807
TI  - A review of background findings in cynomolgus monkeys (Macaca fascicularis) from
      three different geographical origins.
AB  - This review was performed to assess variations in background observations in
      cynomolgus macaques (Macaca fascicularis) originating from three breeding centres
      located in Mauritius, The Philippines and Vietnam. The data and tissue samples
      from 90 cynomolgus monkeys (approximately evenly distributed between the three
      sources) comprising the control groups from 11 regulatory toxicology studies were
      used for this investigation. Clinical data--age, body weight, organ weights,
      haematology and serum biochemistry--were analyzed. Samples of stomach, colon,
      kidney, heart, liver, spleen and lung were examined microscopically and graded to
      characterize the degree of lymphoplasmacytic cell infiltration. The main
      microscopic origin-related variations concerned the digestive tract, where the
      lymphoplasmacytic cell infiltration grade was significantly lower (p0.001) in
      cynomolgus monkeys from Mauritius when compared with those from Asia. Generally,
      only the antral mucosa of the stomach was infiltrated in cynomolgus monkeys from
      The Philippines, whereas both the fundic and antral regions were infiltrated in
      those from Vietnam. The digestive tract infiltration grade was strongly
      correlated with the mean white blood cell count in monkeys from all three
      sources. Spiral-shaped bacteria were observed in the stomach of monkeys from all
      three sources, but their presence did not correlate with the severity of the
      gastric infiltrate. Helicobacter heilmannii-type bacteria were almost always seen
      in the fundus, Helicobacter pylori-type bacteria were only occasionally seen in
      the antral region. The incidences of other microscopic findings, such as
      urothelial cytoplasmic inclusions or Balantidium coli in the caecum, also varied
      according to the source of the monkeys. Some variations in relative organ
      weights, haematology and serum biochemistry were also related to the origin of
      the monkeys, but these did not correlate with the microscopic findings.

PMID- 16984808
TI  - Dynamics of assembly and reorganization of extracellular matrix proteins.
AB  - This chapter will review advances in our understanding of the dynamics of
      assembly and reorganization of extracellular matrix (ECM) proteins and will
      highlight the role of fibronectin as a key orchestrator for the assembly of
      multiple ECM proteins. The dynamic rather than static nature of the ECM will be
      emphasized by reviewing time-lapse imaging studies in living cell and embryo
      systems, with a particular focus on fibronectin and members of the fibrillin
      superfamily. These studies have provided new insights into the assembly and
      reorganization of ECM fibrillar networks, suggesting that fibril assembly is a
      hierarchical process, with increasingly larger fibrillar structures formed by the
      progressive aggregation of smaller units. These studies have also revealed that
      motile cells appear to be actively involved in the assembly and reorganization of
      ECM fibrillar networks by shunting fibrillar material from one location to
      another, adding fibrillar material to the ends of growing fibrils, and exchanging
      material between fibrils. A common theme emerging from these studies is that cell
      and tissue-generated mechanical forces are critical in the assembly and
      remodeling of the ECM.

PMID- 16984809
TI  - Selective neuronal degeneration in Huntington's disease.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder that
      generally begins in middle age with abnormalities of movement, cognition,
      personality, and mood. Neuronal loss is most marked among the medium-sized
      projection neurons of the dorsal striatum. HD is an autosomal dominant genetic
      disorder caused by a CAG expansion in exon 1 of the HD gene, encoding an expanded
      polyglutamine (polyQ) tract near the N-terminus of the protein huntingtin.
      Despite identification of the gene mutation more than a decade ago, the normal
      function of this ubiquitously expressed protein is still under investigation and
      the mechanisms underlying selective neurodegeneration in HD remain poorly
      understood. Detailed postmortem analyses of brains of HD patients have provided
      important clues, and HD transgenic and knock-in mouse models have facilitated
      investigations into potential pathogenic mechanisms. Subcellular fractionation
      and immunolocalization studies suggest a role for huntingtin in organelle
      transport, protein trafficking, and regulation of energy metabolism. Consistent
      with this, evidence from vertebrate and invertebrate models of HD indicates that
      expression of the polyQ-expanded form of huntingtin results in early impairment
      of axonal transport and mitochondrial function. As well, alteration in activity
      of the N-methyl-d-aspartate (NMDA) type glutamate receptor, which has been
      implicated as a main mediator of excitotoxic neuronal death, especially in the
      striatum, is an early effect of mutant huntingtin. Proteolysis and nuclear
      localization of huntingtin also occur relatively early, while formation of
      ubiquitinated aggregates of huntingtin and transcriptional dysregulation occur as
      late effects of the gene mutation. Although each of these processes may
      contribute to neuronal loss in HD, here we review the data to support a strong
      role for NMDA receptor (NMDAR)-mediated excitotoxicity and mitochondrial
      dysfunction in conferring selective neuronal vulnerability in HD.

PMID- 16984810
TI  - RNAi therapy for neurodegenerative diseases.
AB  - RNA interference (RNAi) mediates gene silencing in a sequence-specific manner and
      has proven to be an exceptionally valuable discovery for bench scientists. In the
      laboratory, RNAi technologies provide efficient means for validating drug targets
      and for performing reverse genetics to study gene function (Friedman and
      Perrimon, 2004). Patients may also benefit from RNAi as applications extend to
      potential human therapies. RNAi-based treatments are being investigated and may
      provide hope for patients suffering from cancer, viral infections, or genetic
      diseases for which effective therapies are currently lacking. Notably, several
      independent studies have demonstrated that RNAi therapy can improve disease
      phenotypes in various mouse models of human disease. In this chapter, we focus on
      the potential of RNAi in treating neurologic diseases for which reduction of
      mutant or toxic gene expression may provide therapeutic benefit. We discuss
      approaches to achieving RNAi in vivo, progress in the field, and the potential
      pitfalls associated with RNAi-based therapies.

PMID- 16984811
TI  - Fibrillins: from biogenesis of microfibrils to signaling functions.
AB  - Fibrillins are large proteins that form extracellular microfibril suprastructures
      ubiquitously found in elastic and nonelastic tissues. Mutations in fibrillin-1
      and -2 lead to a number of heritable connective tissue disorders generally termed
      fibrillinopathies. Clinical symptoms in fibrillinopathies manifest in the
      skeletal, ocular, and cardiovascular systems and highlight the importance of
      fibrillins in development and homeostasis of tissues and organs, including blood
      vessels, bone, and eye. Microfibrils appear to have dual roles in (1) conferring
      mechanical stability and limited elasticity to tissues, and (2) modulating the
      activity of growth factors of the transforming growth factor beta (TGF-beta)
      superfamily. This chapter's focus is on the biogenesis of microfibrils,
      developmental expression patterns of fibrillins, signaling functions of
      microfibrils, and mouse models deficient in fibrillins.

PMID- 16984812
TI  - Proteasomes from structure to function: perspectives from Archaea.
AB  - Insight into the world of proteolysis has expanded considerably over the past
      decade. Energy-dependent proteases, such as the proteasome, are no longer viewed
      as nonspecific degradative enzymes associated solely with protein catabolism but
      are intimately involved in controlling biological processes that span life to
      death. The proteasome maintains this exquisite control by catalyzing the
      precisely timed and rapid turnover of key regulatory proteins. Proteasomes also
      interplay with chaperones to ensure protein quality and to readjust the
      composition of the proteome following stress. Archaea encode proteasomes that are
      highly related to those of eukaryotes in basic structure and function.
      Investigations of archaeal proteasomes coupled with those of eukaryotes has
      greatly facilitated our understanding of the molecular mechanisms that govern
      regulated protein degradation by this elaborate nanocompartmentalized machine.

PMID- 16984813
TI  - The cytomatrix as a cooperative system of macromolecular and water networks.
AB  - Water was called by Szent-Gyorgi "life's mater and matrix, mother and medium."
      This chapter considers both aspects of his statement. Many astrobiologists argue
      that some, if not all, of Earth's water arrived during cometary bombardments.
      Amorphous water ices of comets possibly facilitated organization of complex
      organic molecules, kick-starting prebiotic evolution. In Gaian theory, Earth
      retains its water as a consequence of biological activity. The cell cytomatrix is
      a proteinaceous matrix/lattice incorporating the cytoskeleton, a pervasive,
      holistic superstructural network that integrates metabolic pathways. Enzymes of
      metabolic pathways are ordered in supramolecular clusters (metabolons) associated
      with cytoskeleton and/or membranes. Metabolic intermediates are microchanneled
      through metabolons without entering a bulk aqueous phase. Rather than being free
      in solution, even major signaling ions are probably clustered in association with
      the cytomatrix. Chloroplasts and mitochondria, like bacteria and archaea, also
      contain a cytoskeletal lattice, metabolons, and channel metabolites. Eukaryotic
      metabolism is mathematically a scale-free or small-world network. Enzyme clusters
      of bacterial origin are incorporated at a pathway level that is architecturally
      archaean. The eucaryotic cell may be a product of serial endosymbiosis, a
      chimera. Cell cytoplasm is approximately 80% water. Water is indisputably a
      conserved structural element of proteins, essential to their folding,
      specificity, ligand binding, and to enzyme catalysis. The vast literature of
      organized cell water has long argued that the cytomatrix and cell water are an
      entire system, a continuum, or gestalt. Alternatives are offered to mainstream
      explanations of cell electric potentials, ion channel, enzyme, and motor protein
      function, in terms of high-order cooperative systems of ions, water, and
      macromolecules. This chapter describes some prominent concepts of organized cell
      water, including vicinal water network theory, the association-induction
      hypothesis, wave-cluster theory, phase-gel transition theories, and theories of
      low- and high-density water polymorphs.

PMID- 16984814
TI  - Intracellular targeting of phosphodiesterase-4 underpins compartmentalized cAMP
      signaling.
AB  - The phosphodiesterase-4 (PDE4) enzyme belongs to a family of cAMP-dependent
      phosphodiesterases that provide the major means of hydrolyzing and, thereby,
      inactivating the key intracellular second messenger, cAMP. As such, PDE4s are
      central to the regulation of many diverse signaling processes that allow cells to
      respond to external stimuli. Four genes (4A, 4B, 4C, and 4D) encode around 20
      distinct isoform members of the PDE4 family. Each isoform is characterized by a
      unique N-terminal region. PDE4s are multidomain metallohydrolases with each
      domain serving particular roles allowing them to be targeted to varying regions
      and organelles of intracellular space and regulated in distinct fashions by
      phosphorylation and protein-protein interaction. Although identical in catalytic
      function, each isoform locates to distinct regions within the cell so as to
      create and manage spatially distinct pools of cAMP. The multiplicity of partners
      associating with members of the four gene PDE4 family places these enzymes in key
      regulatory positions, permitting them to channel complex biological signals via
      fundamental signaling cohorts such as G-protein-coupled receptors (GPCRs),
      arrestins, A-kinase-anchoring proteins (AKAPs), and tyrosyl family kinases. The
      cAMP cascade has long been linked to cellular growth and embryogenesis and with
      this comes the implication that PDE4 may play considerable roles in the
      regulation of progeny development in maturing cells and tissues.

PMID- 16984815
TI  - Cell biology of membrane trafficking in human disease.
AB  - Understanding the molecular and cellular mechanisms underlying membrane traffic
      pathways is crucial to the treatment and cure of human disease. Various human
      diseases caused by changes in cellular homeostasis arise through a single gene
      mutation(s) resulting in compromised membrane trafficking. Many pathogenic agents
      such as viruses, bacteria, or parasites have evolved mechanisms to subvert the
      host cell response to infection, or have hijacked cellular mechanisms to
      proliferate and ensure pathogen survival. Understanding the consequence of
      genetic mutations or pathogenic infection on membrane traffic has also enabled
      greater understanding of the interactions between organisms and the surrounding
      environment. This review focuses on human genetic defects and molecular
      mechanisms that underlie eukaryote exocytosis and endocytosis and current and
      future prospects for alleviation of a variety of human diseases.

PMID- 16984816
TI  - The biology of the Gaucher cell: the cradle of human chitinases.
AB  - Gaucher disease (GD) is the most common lysosomal storage disorder and is caused
      by inherited deficiencies of glucocerebrosidase, the enzyme responsible for the
      lysosomal breakdown of the lipid glucosylceramide. GD is characterized by the
      accumulation of pathological, lipid laden macrophages, so-called Gaucher cells.
      Following the development of enzyme replacement therapy for GD, the search for
      suitable surrogate disease markers resulted in the identification of a thousand
      fold increased chitinase activity in plasma from symptomatic Gaucher patients and
      that decreases upon successful therapeutic intervention. Biochemical
      investigations identified a single enzyme, named chitotriosidase, to be
      responsible for this activity. Chitotriosidase was found to be an excellent
      marker for lipid laden macrophages in Gaucher patients and is now widely used to
      assist clinical management of patients. In the wake of the identification of
      chitotriosidase, the presence of other members of the chitinase family in mammals
      was discovered. Amongst these is AMCase, an enzyme recently implicated in the
      pathogenesis of asthma. Chitinases are omnipresent throughout nature and are also
      produced by vertebrates in which they play important roles in defence against
      chitin-containing pathogens and in food processing.

PMID- 16984817
TI  - Intracellular signals and events activated by cytokines of the tumor necrosis
      factor superfamily: From simple paradigms to complex mechanisms.
AB  - Tumor necrosis factor (TNF) and several related cytokines can induce opposite
      effects such as cell activation and proliferation or cell death. How the cell
      maintains the balance between these seemingly mutually exclusive pathways has
      long remained a mystery. TNF receptor I (TNFRI) initially emerged as a potent
      activator of NFkappaB and AP-1 transcription factors, while the related CD95
      (Fas, Apo-1) was recognized as a prototype death receptor. Advances in research
      have uncovered critical molecular players in these intracellular processes. They
      have also revealed a much more complex picture than originally thought. Several
      new signaling pathways, including the alternative NFkappaB activation cascade,
      have been uncovered, and previously unknown modes of cross-talk between
      intracellular signaling molecules were revealed. It also turned out that
      signaling mechanisms mediated by the TNF receptor superfamily members can operate
      not only in the immune system but also in organ development.

PMID- 16984818
TI  - Cellular and molecular biology of orphan G protein-coupled receptors.
AB  - The superfamily of G protein-coupled receptors (GPCRs) is the largest and most
      diverse group of membrane-spanning proteins. It plays a variety of roles in
      pathophysiological processes by transmitting extracellular signals to cells via
      heterotrimeric G proteins. Completion of the human genome project revealed the
      presence of approximately 168 genes encoding established nonsensory GPCRs, as
      well as 207 genes predicted to encode novel GPCRs for which the natural ligands
      remained to be identified, the so-called orphan GPCRs. Eighty-six of these
      orphans have now been paired to novel or previously known molecules, and 121
      remain to be deorphaned. A better understanding of the GPCR structures and
      classification; knowledge of the receptor activation mechanism, either dependent
      on or independent of an agonist; increased understanding of the control of GPCR
      mediated signal transduction; and development of appropriate ligand screening
      systems may improve the probability of discovering novel ligands for the
      remaining orphan GPCRs.

PMID- 16984819
TI  - Organization and function of the actin cytoskeleton in developing root cells.
AB  - The actin cytoskeleton is a highly dynamic structure, which mediates various
      cellular functions in large part through accessory proteins that tilt the balance
      between monomeric G-actin and filamentous actin (F-actin) or by facilitating
      interactions between actin and the plasma membrane, microtubules, and other
      organelles. Roots have become an attractive model to study actin in plant
      development because of their simple anatomy and accessibility of some root cell
      types such as root hairs for microscopic analyses. Roots also exhibit a
      remarkable developmental plasticity and possess a delicate sensory system that is
      easily manipulated, so that one can design experiments addressing a range of
      important biological questions. Many facets of root development can be regulated
      by the diverse actin network found in the various root developmental regions.
      Various molecules impinge on this actin scaffold to define how a particular root
      cell type grows or responds to a specific environmental signal. Although advances
      in genomics are leading the way toward elucidating actin function in roots, more
      significant strides will be realized when such tools are combined with improved
      methodologies for accurately depicting how actin is organized in plant cells.

PMID- 16984821
TI  - Evidence-based decision making in small animal therapeutics.
AB  - With a growing number of evidence-based resources being developed for use in
      veterinary medicine, the time is right for academicians, practitioners, and
      students to embrace the positive elements of evidence-based veterinary medicine.
      Clinical pharmacologists, more than most, have all the skills required to use an
      evidence-based approach effectively for the benefit of patients and the
      advancement of the profession.

PMID- 16984822
TI  - Pharmacogenetics.
AB  - Pharmacogenetics, the study of genetic determinants of response to drug therapy,
      is likely the ultimate way to establish the right drug and dose for each patient,
      thereby optimizing efficacy and minimizing toxicity. Despite the fact that this
      branch of pharmacology is still in its infancy as a science, a number of
      important discoveries have already contributed to improved pharmacotherapy in
      human and veterinary patients.

PMID- 16984823
TI  - Cytochrome P450 and its role in veterinary drug interactions.
AB  - Cytochrome P450 (CYP) enzymes are common sites of drug interactions in human
      beings. Drugs may act as inhibitors or inducers of CYPs, leading to altered
      clearance of a second drug. Clinically relevant drug interactions involving
      various CYP isoforms in people, including CYP1A2, CYP2C9, CYP2D6, and CYP3A4,
      have been well documented. Analogous interactions are beginning to be
      characterized in dogs, for which canine CYPs share many of the same substrate
      ranges as in human beings.

PMID- 16984824
TI  - Antimicrobial resistance.
AB  - Development of antimicrobial resistance is an inevitable consequence of exposure
      of microorganisms to antimicrobial agents. Although emergence of resistance
      cannot be prevented, it can be retarded by minimizing use of antimicrobial agents
      and avoiding selection of relatively resistant pathogenic and nonpathogenic
      strains caused by exposure to tissue concentrations that confer a competitive
      advantage. Most attention in veterinary medicine has focused on the emergence of
      resistance in food-borne pathogens, with relatively little attention being
      devoted to small companion animals, despite the frequent use of antimicrobial
      agents in these animals, evidence that resistance is emerging, and potential for
      transfer of resistance between companion animals and people. To retard further
      emergence of resistance in small companion animals, it is imperative that
      surveillance programs be instituted to monitor development of resistance.

PMID- 16984825
TI  - Principles of antimicrobial therapy.
AB  - The most compelling reason for practicing judicious antimicrobial use is to
      facilitate therapeutic success. The definition of therapeutic success has changed
      in recent years, however; not only does success include eradication of infection,
      but it must now include avoidance of resistance. If the goal of antimicrobial
      therapy is to achieve sufficient concentrations at the site of infection such
      that the infecting organism is killed, therapy should be successful.

PMID- 16984826
TI  - Antimicrobial use in the surgical patient.
AB  - Antimicrobials are often used in the surgical patient in an effort to prevent
      infection (prophylactic) or to treat established infection (therapeutic). To be
      effective, prophylactic antimicrobials at appropriate concentrations must be
      present in tissues at the surgical site at the time of contamination to prevent
      bacterial growth and subsequent infection. Therapeutic antimicrobials are used to
      treat established localized or systemic infection. Selection of antimicrobial
      agents for prophylactic or therapeutic use should be based on knowledge of
      expected flora, ability of the antimicrobial to reach the target tissue at
      appropriate concentrations, bacterial resistance patterns, drug pharmacokinetics,
      and culture and susceptibility testing results (therapeutic use). Failure of
      antimicrobial therapy to prevent or treat infection in the surgical patient may
      result from poor antimicrobial selection, inappropriate dosage or frequency, or
      inappropriate duration of therapy.

PMID- 16984827
TI  - The clinical pharmacology of cyclooxygenase-2-selective and dual inhibitors.
AB  - Over the past decade, there have been several nonsteroidal anti-inflammatory
      drugs (NSAIDS) introduced in veterinary medicine with an increased
      gastrointestinal safety profile consistent with a cyclooxygenase (COX)-1-sparing
      effect. More recently, an NSAID with additional 5-lipoxygenase (5-LOX) activity
      has also been approved for use. Although it is tempting to equate in vitro COX
      2/COX-1 and 5-LOX inhibition to overall in vivo safety, the data do not support
      this approach. The true overall safety for any individual compound is based on
      its evaluation in laboratory margin-of-safety studies, reproductive safety
      studies, and blind multicenter field studies in client-owned animals. Therefore,
      when choosing a COX-2-selective or dual-inhibitor NSAID for clinical use, all in
      vivo data must be taken into account to understand comparative safety, and
      continued use must be based on the drug's performance in the individual being
      treated. Until head-to-head trials in multicenter blind studies are published,
      comments on comparative safety and effectiveness must be reserved.

PMID- 16984828
TI  - Update on drugs used to treat endocrine diseases in small animals.
AB  - Drug therapy for the endocrine system is implemented to replace a hormone
      deficiency or to prevent or reduce the formation or effects of excess hormone.
      Treatment of endocrine disorders covers diseases of the pituitary, adrenal,
      parathyroid, and thyroid glands as well as the endocrine pancreas. This article
      focuses on new therapies currently available for specific diseases.
      Administration of trilostane for treatment of hyperadrenocorticism and use of
      insulin glargine, protamine zinc insulin (PZI), and porcine Lente insulin for
      diabetes mellitus are discussed. In addition, transdermal methimazole therapy for
      treatment of feline hyperthyroidism and administration of progestins for
      pituitary dwarfism are considered.

PMID- 16984829
TI  - Anticonvulsant therapy in dogs and cats.
AB  - This article reviews anticonvulsant therapies in current use for dogs and cats
      and briefly describes new modes of anticonvulsant therapy that are being
      investigated or pending publication. Most of the information contained within the
      article is based on published information. Some of the information, however, is
      based on the author's clinical experience and is identified as such.

PMID- 16984830
TI  - Veterinary compounding in small animals: a clinical pharmacologist's perspective.
AB  - The advent and growth of veterinary compounding and the increasing role of the
      pharmacist in drug dispensing, including compounding, should be embraced by the
      veterinary profession. For selected patients, extemporaneous compounding of
      prescriptions is necessary and beneficial for optimal treatment. By its nature,
      however, compounding is individualized and fraught with risks of failure. Pet
      owners should be informed of the risks associated with using a compounded product
      and consent to therapy based on disclosure that the use of the product may be
      scientifically unproven. As the pharmacy profession increases its efforts to
      define and ensure its role in veterinary medicine, and as the regulatory agencies
      consider changes in the regulations that increase the flexibility of animal drug
      compounding, the veterinary profession must implement actions that protect the
      patient and the public. It is indeed the responsibility of the veterinarian to
      ensure the safety and therapy of any prescribed therapeutic intervention, and
      failure to do otherwise places the patient and pet owner as well as the
      veterinarian at risk.

PMID- 16984831
TI  - Top-cited articles in emergency medicine.
AB  - STUDY OBJECTIVE: Our purpose was to identify and examine the characteristics of
      the most frequently cited articles in the field of emergency medicine (EM).
      METHODS: Top-cited EM articles in 9 EM journals were identified by searching the
      computerized database of the Science Citation Index Expanded and the Web of
      Science (1972 to present). Median citation numbers, authors' nationalities,
      publication year, and fields of study were described and discussed. Mann-Whitney
      U and Kruskal-Wallis tests were used to compare groups. RESULTS: All top-cited
      articles were published during 1972 and 2002. We identified 100 top-cited
      articles published in 6 EM journals, led by Annals of Emergency Medicine (66) and
      American Journal of Emergency Medicine (22). Toxicology, traumatology,
      resuscitation medicine, and cardiovascular medicine were the primary focus of
      study. The median citation number for these top-cited articles was 102 (range, 71
      335). CONCLUSION: Our analysis gives an encyclopedic review of citation frequency
      of top-cited articles published in EM journals, which may provide information for
      those who want to find the history, evolution, and areas of high-impact research
      activities of EM.

PMID- 16984832
TI  - Prevalence of life-threatening arrhythmias in ED patients transported to the
      radiology suite while monitored by telemetry.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of life
      threatening arrhythmias in monitored ED patients while in the radiology suite.
      METHODS: This is a retrospective analysis at a tertiary care hospital with an ED
      census of 52,000 visits. The patient population consisted of 3,051 adult ED
      patients with a chief complaint of chest pain, who were monitored with telemetry
      while they were sent to the radiology suite, and who were ultimately admitted to
      the hospital. RESULTS: Of a total of 3,051 consecutive patients with a cardiac
      presentation who received a nonportable chest x-ray, no patients were found to
      have incurred a life-threatening arrhythmia while in the radiology suite.
      CONCLUSION: The prevalence of a cardiac arrhythmia occurring during transport or
      while within the radiology suite in our study was zero. We conclude that stable
      patients can probably be transported to radiology safely without the use of
      bedside telemetry.

PMID- 16984833
TI  - A prospective study on esophageal Doppler hemodynamic assessment in the ED.
AB  - We sought to determine whether physicians' estimates of critically ill patients'
      hemodynamics are accurate as compared with esophageal Doppler probe (EDP)
      measurements and whether provision of measured hemodynamic profiles produces
      treatment changes and changes in physician confidence. At an urban county ED, we
      enrolled 55 critically ill adults with pulmonary edema of unclear etiology,
      sustained hypotension, or lactic acidosis. Physicians estimated cardiac output
      (CO) and systemic vascular resistance (SVR), categorized shock, stated treatment
      plans, and rated confidence in assessment and treatment plans. Physicians were
      informed of EDP hemodynamic measurements (CO, SVR, stroke volume, and
      contractility), and they repeated their assessments and plans. Weighted kappa
      values between physician estimates and EDP measurements of CO and SVR were 0.57
      (95% confidence interval [CI] = 0.77-0.36) and 0.40 (95% CI = 0.64-0.16),
      respectively. Shock characterization changed in 52%, confidence increased
      significantly (pre-EDP mean = 3.3 +/- 0.9; post-EDP mean = 4.0 +/- 0.6; P =
      .0001), and stated treatment plans changed in 68% of the patients. Chart review
      demonstrated that similar proportions of control subjects had treatment changes,
      with a mean difference of 20% (95% CI = -2 to 42). Physician assessments of
      hemodynamic variables were moderately accurate. We conclude that EDP hemodynamic
      profiles change assessments and increase confidence in assessments but may not
      alter treatment.

PMID- 16984834
TI  - Documentation and coding of ED patient encounters: an evaluation of the accuracy
      of an electronic medical record.
AB  - OBJECTIVE: The aim of the study was to describe a paper-based, template-driven
      and an electronic medical record used for capturing emergency care clinical
      information and to compare the accuracy of these documentation systems for coding
      patient encounters using the American Medical Association Current Procedural
      Terminology-2004 (AMA CPT-2004) evaluation and management codes intended for
      provider reimbursement. METHODS: A retrospective, cross-sectional study of 4
      consecutive-day samples of ED patient encounter records from 2 similar community
      hospitals was done. For clinical documentation, hospital A uses an electronic
      medical record, whereas hospital B uses a paper-based template-driven record.
      Using a simple analytic model, expert coders A and B, respectively, coded the
      records from hospitals A and B for completeness. First, power analysis determined
      the acceptability of the patient record sample sizes (1 - beta = .90 at 1%
      significance level), and the frequency of AMA CPT-2004 primary evaluation and
      management codes 99281 through 99285 was calculated. Second, the completeness
      discrepancy rates for hospitals A and B were compared to determine the accuracy
      of both the paper-based, template-driven record and the electronic medical record
      in documenting and representing the clinical encounter. Third, interrater
      reliability between expert coders A and B was calculated to assess the level of
      agreement between each expert coder in determining the completeness discrepancy
      rates between hospitals A and B. Finally, the frequency of primary evaluation and
      management codes was analyzed to determine if there was a statistically
      significant difference between the paper-based, template-driven record and the
      electronic medical record representation of the clinical information, and if that
      difference could be attributable to the differing clinical documentation systems
      used in hospitals A and B. RESULTS: First, descriptive display demonstrated a
      difference in the frequency of the primary evaluation and management codes 99283
      and 99284 within hospital A (expert coder A assessment, 36.1% vs 39.1%; expert
      coder B assessment, 36.6% vs 38.7%) and hospital B (expert coder A assessment,
      47.8% vs 21.9%; expert coder B assessment, 48.6% vs 21.4%) was noted with the
      median, primary evaluation, and management code for hospital A of 99284 and the
      median, primary evaluation, and management code for hospital B of 99283. Second,
      Fisher exact test compared the completeness discrepancy rates between hospitals A
      and B as assessed by each expert coder and demonstrated no statistically
      significant difference in the completeness discrepancy rates (accuracy) between
      the paper-based, template-driven record and the electronic medical record
      documentation and coding system when assessed by either expert coder A (P = .370)
      or expert coder B (P = .819). Third, interrater reliability between expert coders
      A and B was evaluated using Cohen's kappa statistic. When evaluated both
      individually and jointly with respect to hospitals A and B, expert coders A and B
      had a good strength of agreement in their assessments of the accuracy of the
      documentation and coding system for hospital A (kappa = 0.6200) and hospital B
      (kappa = 0.6906) as well as for both hospitals evaluated together (kappa =
      0.6616). Finally, interhospital differences in the frequency of primary
      evaluation and management codes were evaluated using Pearson chi(2) test with 3
      df. The results for expert coder A (chi(2) = 47.4160; P < .001) and expert coder
      B (chi(2) = 46.5946; P < .001) recognize that there is a statistically
      significant degree of difference between hospitals A and B in the frequency
      distribution of primary evaluation and management codes, probably because of the
      dispersion of codes 99283 and 99284. CONCLUSIONS: A keystroke-driven, electronic
      medical record that resides on a knowledge platform that incorporates a clinical
      structured terminology, administrative coding schemata, AMA CPT-2004 codes and
      uses object-oriented, open-ended, branching chain clinical algorithms that
      "force" physician documentation of the clinical elements provides an equally
      accurate capture and representation of ED clinical encounter data as a paper
      based, template-driven documentation system both in terms of the presence or
      absence of both the medically necessary, discrete data elements and the textual
      documentation-dependent, medical decision-making elements.

PMID- 16984835
TI  - Predictive values of triage temperature and pulse for antibiotic administration
      and hospital admission in elderly patients with potential infection.
AB  - To determine how well triage temperature and pulse abnormalities in elderly
      patients with potential infections predict antibiotic administration and hospital
      admission. Data from the National Hospital Ambulatory Care Survey (2001-2002), a
      sample of US emergency departments, were used. Patients (>or=65 years) with a
      reason for visit suggesting potential infection were included. Of 10,586 patients
      65 years or older, 32% had reasons for visit suggesting potential infection. The
      negative predictive value for predicting intensive care unit admission (n = 154)
      for triage hyperthermia (temperature >or=38 degrees C) was 96% (95% confidence
      interval, 95%-96%); hypothermia (temperature <or=36 degrees C), 95% (95%-96%);
      pulse higher than 90, 97% (96%-98%); both pulse higher than 90 and hypothermia or
      hyperthermia, 96% (95%-96%); and either pulse higher than 90 or hypothermia or
      hyperthermia, 96% (95%-97%). The negative predictive value for the combined
      outcome of hospital admission and antibiotic administration (n = 432) for
      hyperthermia was 90% (88%-91%); hypothermia, 87% (86%-88%); pulse higher than 90,
      90% (89%-92%); for both pulse higher than 90 and hypothermia or hyperthermia, 89%
      (88%-90%); and for either pulse higher than 90 or hypothermia or hyperthermia,
      91% (90%-93%). Although the absence of pulse and temperature abnormalities in
      elderly patients with potential infection is predictive of not being admitted to
      the intensive care unit and the combined outcome of admission and
      hospitalization, this information should not be used alone to determine the
      presence or absence of a potentially time-sensitive infection.

PMID- 16984837
TI  - Bedside lung ultrasound in the assessment of alveolar-interstitial syndrome.
AB  - OBJECTIVES: To assess the potential of bedside lung ultrasound to diagnose the
      radiologic alveolar-interstitial syndrome (AIS) in patients admitted to an
      emergency medicine unit and to estimate the occurrence of ultrasound pattern of
      diffuse and multiple comet tail artifacts in diseases involving lung
      interstitium. METHODS: The ultrasonic feature of multiple and diffuse comet tail
      artifacts B line was investigated in each of 300 consecutive patients within 48
      hours after admission to our emergency medicine unit. Sonographic examination was
      performed at bedside in a supine position. Eight anterolateral ultrasound chest
      intercostal scans were obtained for each patient. RESULTS: The artifact showed a
      sensitivity of 85.7% and a specificity of 97.7% in recognition of radiologic AIS.
      Corresponding figures in the identification of a disease involving lung
      interstitium were 85.3% and 96.8%. CONCLUSION: Comet tail artifact B line is a
      lung ultrasound sign reasonably accurate for diagnosing AIS at bedside.

PMID- 16984836
TI  - Relative adrenal insufficiency after cardiac arrest: impact on postresuscitation
      disease outcome.
AB  - The purpose of this study is to prospectively evaluate the cortisol response and
      determine the relative adrenal insufficiency after return of spontaneous
      circulation (ROSC). METHODS: This is a prospective cohort study describing the
      prevalence of relative adrenal insufficiency in consecutive patients admitted to
      an intensive care unit following ROSC (>24 hours) after cardiac arrest. The study
      institution is a 1,300-bed urban hospital with an annual intensive care unit
      census of 80. Descriptive statistics is used to report results. RESULTS: This
      study included 30 patients over a 1-year period. The mean patient age was 52
      years, and there were 15 (50%) males. The most common etiology for cardiac arrest
      was unknown, and the most common initial rhythm was asystole. There were 16 (53%)
      witnessed arrests. The mean time from arrest to cardiopulmonary resuscitation was
      8 minutes, and the mean time from arrest to ROSC was 23 minutes. Relative adrenal
      insufficiency (incremental response to corticotrophin test < 9 microg/dL) at
      initial 12 to 24 hours and >24 to 48 hours occurred in 13 (43%) and 10 (33%)
      patients, respectively. All basal cortisol values were normal to high. Nineteen
      (58%) patients survived. The mean cortisol values at the initial 12 to 24 hours
      and >24 to 48 hours were similar among survivors and nonsurvivors. Relative
      adrenal insufficiency was present in only 5 (26%) survivors. CONCLUSION: Relative
      adrenal insufficiency may be associated with the increased mortality rate in
      patients with return of circulation after cardiac arrest. Although basal cortisol
      values were normal to high, treatment of relative adrenal insufficiency with
      corticosteroids may decrease the mortality rate. Additional studies are needed to
      confirm this association and to determine the effectiveness of treating relative
      adrenal insufficiency.

PMID- 16984838
TI  - A new method of internal jugular vein catheterization using the cricoid cartilage
      and the external jugular vein as a landmark.
AB  - PURPOSE: The aim of this study was to find a new external landmark for internal
      jugular vein (IJV) catheterization. METHODS: The locations of the right IJVs of
      100 patients were examined by ultrasonography using the external jugular vein and
      the cricoid cartilage as landmarks, and in a clinical study, we catheterized the
      right IJVs of 100 patients using these landmarks. RESULTS: By ultrasonography,
      the average distance from point A (a point 1.5 cm medial from the external
      jugular vein at the cricoid cartilage level) to the midpoint of the right IJV was
      0.35 +/- 0.61 cm, and by clinical study, catheterization of the right IJV was
      successful in 99% (99/100) of patients. Patients required an average of 1.75 +/-
      0.75 attempts, and no carotid puncture occurred. CONCLUSIONS: This new method of
      IJV catheterization was found to have a high success rate and few complications.

PMID- 16984839
TI  - Transarterial embolization of acute external carotid blowout syndrome with
      profuse oronasal bleeding by N-butyl-cyanoacrylate.
AB  - OBJECTIVES: Assess duration, efficacy, and safety of emergent transarterial
      embolization of acute external carotid blowout syndrome (ECBS) with N-butyl
      cyanoacrylate. METHODS: Medical records were reviewed for 16 patients (15 men, 1
      woman; age range, 28-85 years) who had 17 acute ECBS events that presented with
      profuse transoronasal bleeding. Predisposing factors were carcinoma associated
      with surgery and/or radiotherapy (n = 14) or trauma (n = 3). Affected arteries
      were the internal maxillary artery (n = 5), superior thyroid artery (n = 4),
      lingual artery (n = 4), facial artery (n = 2), or ascending pharyngeal artery (n
      = 2). RESULTS: Endovascular treatment successfully obliterated all acute ECBSs
      with cessation of profuse hemorrhage. Mean duration of procedure was 54 minutes.
      Three patients had recurrent carotid blowout syndrome events, with 1 resulting
      death. Clinical follow-up range was 2 to 23 months. CONCLUSIONS: Transarterial N
      butyl-cyanoacrylate embolization can successfully manage acute ECBS with profuse
      hemorrhage. The technique is both efficient and safe, and the procedure can be
      rapidly completed.

PMID- 16984840
TI  - The relationship of air pollution to ED visits for asthma differ between children
      and adults.
AB  - The purpose of this study was to evaluate the relationship between air pollution
      and asthma exacerbation in children and adults. Pearson analysis was used to
      establish correlations between air pollutants-sulfur dioxide, nitrogen dioxide,
      ozone, carbon monoxide, and particles with an aerodynamic diameter of 10 microm
      or less (PM(10))--and ED visits for asthma in 2004. Among children, there were
      significant positive correlations between nitrogen dioxide (r = 0.72), carbon
      monoxide (r = 0.65), and PM(10) (r = 0.63) and ED visits for asthma. Among
      adults, only weakly positive, non significant correlations between all air
      pollution measures and ED visits for asthma were found. This study suggests that
      air pollution plays a role in acute exacerbation of asthma in children but not in
      adults.

PMID- 16984841
TI  - Weight-reducing regimen associated with polymorphic ventricular tachycardia.

PMID- 16984842
TI  - Electrical alternans in a patient with pleural effusions.

PMID- 16984843
TI  - Poor glycemic control in diabetic patients seeking care in the ED.
AB  - We hypothesized that diabetic patients in the emergency department (ED) have
      poorer glycemic control than patients seeking care at primary care clinics. A
      convenience sample of hemoglobin A1c (HbA1c) values was gathered retrospectively
      from the ED, Endocrinology, and Family Medicine Clinics. Results were divided
      into controlled, poorly controlled, and extremely poorly controlled. The only
      differing pattern of patients (*P < .01) was in the extremely poorly controlled
      group consisting of 36% of the ED patients (confidence interval [CI], 29.23
      42.69; n = 74) vs 18% of the Endocrinology patients (CI, 13.76-22.53; n = 56) and
      19% of the Family Medicine patients (CI, 15.98-22.75; n = 105). A frequency
      distribution of the ED HbA1c values was bimodal. The first peak represents well
      controlled diabetic patients. The second, higher peak comprises a larger number
      of patients (approximate n = 134, 73% of all 207 ED patients) who have poorer
      glycemic control. We conclude that a large number of ED diabetic patients have
      poorer glycemic control than the other clinics.

PMID- 16984844
TI  - Inhalational abuse of methanol products: elevated methanol and formate levels
      without vision loss.
AB  - Inhalant abuse of methanol-containing products has increased over the last
      decade. We performed a prospective observational study of 7 subjects who
      presented to an ED after inhalant abuse of methanol-containing hydrocarbon
      products. Four patients had a methanol level greater than 24 mg/dL and 2 had an
      anion gap greater than 17 mEq/L. The mean formic acid level was 71 microg/mL, and
      1 patient had a level considered high enough to induce retinal toxicity (>200
      microg/mL). No patient had an abnormal ophthalmologic examination. All patients
      were treated with intravenous folate, 2 received alcohol dehydrogenase blockade,
      and no patient received hemodialysis or intravenous bicarbonate. All patients'
      acidosis resolved within 4 hours. The methanol and formic acid levels are lower
      than those reported after methanol ingestion. These preliminary data suggest that
      inhalant abusers of methanol products may have significantly elevated methanol
      and formic acid levels, but are at low risk for methanol induced complications of
      visual dysfunction and refractory acidosis.

PMID- 16984845
TI  - Is digital intubation an option for emergency physicians in definitive airway
      management?
AB  - OBJECTIVES: This study was designed to determine whether digital intubation is a
      valid option for definitive airway control by emergency physicians. METHODS:
      Digital intubation was performed by 18 emergency medicine residents and 4 staff
      emergency medicine physicians on 6 different cadavers. Placement was confirmed by
      direct laryngoscopy. The total time for all attempts used, as well as the number
      of attempts, was recorded. Each participant attempted intubation on all 6
      cadavers. RESULTS: For 5 of the 6 cadavers, successful intubation occurred 90.9%
      of the time (confidence interval [CI], 85.5%-96.3%) for all participants. The
      average number of attempts for these 5 cadavers was 1.5 (CI, 1.4-1.7), and the
      average time required for success or failure was 20.8 seconds (CI, 16.9-24.8).
      The sixth cadaver developed soft tissue damage and a false passage near the vocal
      cords resulting in multiple failed attempts. CONCLUSIONS: Although the gold
      standard for routine endotracheal intubation remains to be direct laryngoscopy,
      its effectiveness in certain situations may be limited. We believe that digital
      intubation provides emergency physicians with another option in securing the
      unprotected airway.

PMID- 16984846
TI  - Spontaneous coronary artery dissection in a patient presenting with atypical
      chest pain.

PMID- 16984847
TI  - MDMA-induced acute pulmonary edema in a patient without other organ dysfunction.

PMID- 16984848
TI  - Spontaneous spinal epidural hematomas of cervical spine: report of 4 cases and
      literature review.

PMID- 16984849
TI  - A potentially fatal mystery in acute abdomen: abdominal apoplexy.

PMID- 16984850
TI  - Lunesta overdose: ST-elevation coronary vasospasm, troponemia, and ventricular
      fibrillation arrest.

PMID- 16984851
TI  - False-negative cerebral infarction on diffusion magnetic resonance imaging.

PMID- 16984852
TI  - Hemodialysis and hemoperfusion in a patient with an isolated phenytoin overdose.

PMID- 16984853
TI  - A case report of emphysematous pyelonephritis secondary to ureteral obstruction
      in a non-diabetic patient.

PMID- 16984854
TI  - Respiratory failure due to subglottic stenosis from relapsing polychondritis.

PMID- 16984855
TI  - Noninvasive capnometry for continuous monitoring of mental status: a tale of 2
      patients.

PMID- 16984856
TI  - Tuberculosis mycobacterium sepsis as a rare cause of out-of-hospital cardiac
      arrest.

PMID- 16984857
TI  - Malpractice and criminal responsibility in Japan.

PMID- 16984858
TI  - Comment on "Is prehospital blood glucose measurement necessary in suspected
      cerebrovascular accident patients?".

PMID- 16984859
TI  - Postdural puncture headache after lumbar puncture: do the gauge and the design of
      a spinal needle matter?

PMID- 16984861
TI  - Trends in the use of ipecac in the ED setting: data from the 1992-2002 NHAMCS-ED
      (letter).

PMID- 16984862
TI  - Defining what doctors and patients mean by intimate partner violence--do they
      mean the same thing?

PMID- 16984863
TI  - Reply to letter to the editor by Perrone.

PMID- 16984864
TI  - Spinal cord infarction after weight lifting (Am J Emerg Med. 2006 May;24(3):352
      5).

PMID- 16984866
TI  - Invasive candidiasis.
AB  - Invasive candidiasis remains an important nosocomial infection that continues to
      present major diagnostic and therapeutic challenges to the clinician. Changes in
      the epidemiology of this disorder have occurred for many reasons, and included
      especially the extensive use of prophylactic antifungal agents, broad-spectrum
      antibacterial agents, and medical devices (eg, chronic indwelling intravascular
      catheters). The diagnosis of IC remains elusive in many patients, and there is a
      critical need for improved diagnostics that will provide clinicians the
      opportunity to intervene earlier in the course of disease. Newer antifungal
      agents offer promise in the treatment of candidemia and other forms of IC, but
      the optimal use of these agents, particularly in the approach to non-albicans
      Candida infections, needs to be explored in more detail. Furthermore, despite an
      overwhelming amount of data concerning risk factors and excess mortality
      associated with the development of IC, there is no consistent approach to
      treatment and primary prevention among individuals who are deemed to be at
      highest risk for this complication. Research that focuses on these important
      clinical areas could provide valuable insights into the diagnosis and management
      of this common and evolving infection.

PMID- 16984867
TI  - Cryptococcosis.
AB  - In the past 2 decades, Cryptococcus has emerged in its clinical significance and
      as a model yeast for understanding molecular pathogenesis. C neoformans and C
      gattii are currently considered major primary and secondary pathogens in a wide
      array of hosts that are known to be immunocompromised or apparently
      immunocompetent. A recent outbreak of C gattii infections further underscores the
      clinical importance of the yeast through its epidemiology and pathogenicity
      features. With an enlarging immunosuppressed population caused by HIV infection,
      solid organ transplantation, and clinical use of potent immunosuppressives, such
      as cancer chemotherapy, monoclonal antibodies, and corticosteroids, this fungus
      has become a well-established infectious complication of modern medicine. This
      article examines current issues in cryptococcal infections, including new
      classification, epidemiology, pathogenesis, and specific clinical aspects.

PMID- 16984868
TI  - Aspergillosis: spectrum of disease, diagnosis, and treatment.
AB  - Infections by Aspergillus species present a particular challenge. The organism,
      which is ubiquitous in the environment, causes allergic disease in otherwise
      healthy individuals and devastating disease in the immunosuppressed. This article
      examines the range of infections caused by Aspergillus species, the challenges of
      diagnosis, and current treatment options.

PMID- 16984869
TI  - Emerging fungi.
AB  - The hyalohyphomycetes (especially Fusarium spp) have emerged as significant
      pathogens in severely immunocompromised patients. Human infections by Fusarium
      spp can be superficial or limited to single organs in otherwise healthy patients.
      Such infections are rare and tend to respond well to therapy. By contrast,
      disseminated fusarial hyalohyphomycosis affects the immunocompromised host and
      frequently is fatal. Successful outcome is determined by the degree of
      immunosuppression and the extent of the infection. These infections may be
      suspected clinically on the basis of a constellation of clinical and laboratory
      findings, which should lead to prompt therapy.

PMID- 16984870
TI  - Invasive zygomycosis: update on pathogenesis, clinical manifestations, and
      management.
AB  - Zygomycosis is an increasingly common infection in immunocompromised patients.
      Advances in the understanding of Zygomycetes pathobiology and the introduction of
      new drugs with improved activity and tolerability for treatment of zygomycosis
      have improved the prospects of effectively controlling this devastating
      infection. Further reductions in mortality will require improved diagnostic and
      novel therapeutic approaches for this group of aggressive opportunistic molds.

PMID- 16984871
TI  - Phaeohyphomycosis.
AB  - Phaeohyphomycosis is an uncommon infection, but has become increasingly
      recognized in a wide variety of clinical syndromes. Many species are associated
      with human infection, though a few are responsible for most cases. Because these
      are typically soil organisms and common laboratory contaminants, they are often
      disregarded from clinical specimens as non-pathogenic. The clinical setting in
      which they are isolated, however, should always be carefully considered before
      making decisions regarding therapy. Bipolaris and Curvularia are often associated
      ith allergic disease. Diagnosis depends on a high degree of clinical suspicion
      and appropriate pathologic and mycologic examination of clinical specimens.
      Therapy is evolving for many of the clinical syndromes described, and randomized
      clinical trials are unlikely given the sporadic nature of cases. Case reporting
      of successful and unsuccessful clinical experiences is important in attempting to
      better define optimal therapy for the more refractory infections. Itraconazole
      and voriconazole demonstrate the most consistent in vitro activity against this
      group of fungi. Itraconazole should be considered the drug of choice for most
      situations, given the greater clinical experience associated with its use for
      these infections. Given the lack of comparative clinical data, however, decisions
      over which azole to use in particular setting are largely empiric. Much
      additional work is needed to better understand the pathogenic mechanisms
      underlying phaeohyphomycosis and optimize therapy for these often refractory
      infections.

PMID- 16984872
TI  - Coccidioidomycosis.
AB  - The difficulties in managing this potentially horrific disease, with its myriad
      manifestations, are immense, because host factors dramatically impact outcome.
      Coccidioidomycosis should warrant great respect among clinicians, because, even
      with dramatic improvements in therapies, outcomes remain poor. Although there
      have been outstanding successes with these new therapies, tragic losses after
      years of immense patient suffering still occur. Coccidioidomycosis is a
      geographically restricted fungus but is one that inflicts tremendous suffering on
      affected patients. In addition, because of travel and the influx of susceptible
      hosts, dramatic increases in patients at risk for infection are seen throughout
      the southwest United States. The extended-spectrum azoles, such as posaconazole
      and voriconazole, may prove to be more efficacious in the treatment of
      coccidioidomycosis than prior agents, including amphotericin B, fluconazole, and
      itraconazole. Additional resources are needed to conduct randomised, controlled
      clinical trials for the treatment of this disease.

PMID- 16984873
TI  - Endemic mycoses: blastomycosis, histoplasmosis, and sporotrichosis.
AB  - The endemic mycoses are diverse group of fungi that share several
      characteristics. They are able to cause disease in healthy hosts, they each
      occupy a specific ecologic niche in the environment, and they exhibit temperature
      dimorphism, existing as molds in the environment at temperature of 25 degrees C
      to 30 degrees C, and as yeasts, or spherules in the case of coccidioidomycosis,
      at body temperatures. This article discusses histoplasmosis and blastomycosis.
      Sporotrichosis, which differs in that it is usually a localized lymphocutaneous
      infection, is included because it shares the characteristics of endemic mycoses.

PMID- 16984874
TI  - Mycoses in pediatric patients.
AB  - For more than 40 years, there has been limited progress in the treatment of
      invasive fungal infections. There are now numerous nuances to choosing the
      appropriate antifungal agent. Important advantages have been achieved in
      understanding the safety, tolerability, and pharmacokinetics of these agents. One
      of the most important aspects for successful management of pediatric invasive
      fungal infections is an understanding of the differences in the pharmacokinetics
      of the drugs in children and adults to offer optimal dosing strategies.
      Unfortunately there have been few antifungal studies conducted in children.
      Consequently most information for the pediatrician has been extrapolated from
      adult data. The breadth of antifungal data in children is expanding, however,
      with newer studies underway. Through the efforts of dedicated clinicians and
      collaboration, pediatric indications and dosing strategies will eventually be
      discovered that directly benefit pediatric patients.

PMID- 16984875
TI  - Pharmacokinetics and pharmacodynamics of antifungals.
AB  - Application of pharmacodynamic principles to antifungal drug therapy of Candida
      and Aspergillus infections has provided and understanding of the relationship
      between drug dosing and treatment efficacy. Observations of the pharmacodynamics
      of triazoles and AmB have correlated with the results of clinical trials and have
      proven useful for validation of in vitro susceptibility breakpoints. Although
      there remain many unanswered questions regarding antifungal pharmacodynamics,
      available data suggest usefulness in the application of pharmacodynamics to
      antifungal clinical development. Future application of these principles should
      aid in the design of optimal combination antifungal therapies.

PMID- 16984876
TI  - Antifungal susceptibility testing.
AB  - Antifungal susceptibility testing has been in routine use now for more than 15
      years and has become a useful tool for clinicians who are faced with difficult
      treatment decision. Although most clinicians order susceptibility testing, much
      confusion still exists regarding the use of the results. Sufficient data have
      been generated to determine susceptibility trends for specific fungi against
      specific agents, but correlation data are minimal. Despite the lack of
      correlation data, antifungal susceptibility testing continues to provide useful
      information to assist with patient care.

PMID- 16984877
TI  - Non-culture-based diagnostics for opportunistic fungi.
AB  - The value of the diagnostic markers galactomannan and 1,3-beta-D-glucan for the
      diagnosis of opportunistic fungal infections is reviewed in this article. Both
      markers have undergone clinical evaluation, and increasing insight is emerging
      with respect to the causes of false-negative or false-positive reactivity. These
      data will help design protocols in which single or multiple markers are used to
      identify patients who require antifungal therapy.

PMID- 16984878
TI  - Spray-on special effects. Mendel Biotechnology uses chemical genetics to help
      plants cope with stress.

PMID- 16984879
TI  - Fine-tuning ER-beta structure with PTMs.
AB  - Estrogen receptor beta is differentially regulated by alternative O
      GlcNAcylation/O-phosphorylation at Ser(16). NMR, CD, and molecular dynamics
      analyses of model peptides show that these alternative modifications induce
      different peptide conformations, providing a molecular basis for their
      differential regulation of protein function.

PMID- 16984880
TI  - A noncanonical path to mechanism of action.
AB  - Improved methods for discovering small-molecule mechanisms of action are needed.
      In this issue of Chemistry & Biology, Zhang et al. make clever use of the
      zebrafish to study the mechanism of the angiogenesis inhibitor fumagillin and
      reveal that it targets the noncanonical Wnt pathway.

PMID- 16984881
TI  - A stability switch for proteins.
AB  - A paper published in the September 8 issue of Cell describes a generally
      applicable approach for chemical control of protein stability, with potential for
      broad use in chemical genetics.

PMID- 16984882
TI  - Replacement surgery with unnatural amino acids in the lock-and-key joint of
      glutathione transferase subunits.
AB  - Proteins contain amino acid residues essential to structure and function.
      Ribosomal protein synthesis is typically limited to the 20 amino acids of the
      genetic code, but posttranslational chemical modifications can greatly expand the
      diversity of side chain functionalities. In this investigation, a natural
      aromatic residue in the lock-and-key joint at the subunit interface of the
      dimeric glutathione transferase P1-1 was replaced by an S-alkylcysteine residue
      to give a functional enzyme. Introduction of Cys in the key position inactivates
      the enzyme, but subsequent alkylation of this residue enhances the catalytic
      efficiency up to 27,000-fold. Combinatorial modification of Cys by a mixture of
      reagents facilitated identification of an n-butyl group as the most efficient
      activator. Alkylation also enhanced binding affinity for active-site ligands and
      stabilized the enzyme against chemical denaturation and thermal inactivation.

PMID- 16984883
TI  - Alternative O-GlcNAcylation/O-phosphorylation of Ser16 induce different
      conformational disturbances to the N terminus of murine estrogen receptor beta.
AB  - Serine and threonine residues in many proteins can be modified by either
      phosphorylation or GlcNAcylation. To investigate the mechanism of O-GlcNAc and O
      phosphate's reciprocal roles in modulating the degradation and activity of murine
      estrogen receptor beta (mER-beta), the conformational changes induced by O
      GlcNAcylation and O-phosphorylation of Ser(16) in 17-mer model peptides
      corresponding to the N-terminal intrinsically disordered (ID) region of mER-beta
      were studied by NMR techniques, circular dichroism (CD), and molecular dynamics
      simulations. Our results suggest that O-phosphorylation discourages the turn
      formation in the S(15)STG(18) fragment. In contrast, O-GlcNAcylation promotes
      turn formation in this region. Thus, we postulate that the different changes of
      the local structure in the N-terminal S(15)STG(18) fragment of mER-beta caused by
      O-phosphate or O-GlcNAc modification might lead to the disturbances to the
      dynamic ensembles of the ID region of mER-beta, which is related to its
      modulatory activity.

PMID- 16984884
TI  - Identification of NanE as the thioesterase for polyether chain release in
      nanchangmycin biosynthesis.
AB  - The polyketide synthase (PKS) for the biosynthesis of the polyether nanchangmycin
      lacks an apparent thioesterase comparable to the type I thioesterase domains of
      the modular PKSs responsible for macrolide biosynthesis. Three candidate
      polyether chain-releasing factors were examined. Both the putative CR domain and
      the NanE protein appeared to be genetically relevant. Among the three
      heterologously expressed soluble proteins (recombinant CR domain, the ACP-CR
      didomain, and NanE) tested, only NanE hydrolyzed the polyether-SNAC. By contrast,
      recombinant DEBS TE from the erythromycin pathway, and the recombinant MonAX, a
      type II TE associated with the polyether monensin biosynthesis for which a
      homolog has not been detected in the nanchangmycin cluster, hydrolyzed a diketide
      SNAC but not the polyether-SNAC. We could thus conclude that NanE is a dedicated
      thioesterase mediating the specific release of the polyether chain during
      nanchangmycin biosynthesis.

PMID- 16984885
TI  - The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes.
AB  - The maintenance of self-renewal in stem cells appears to be distinct from the
      induction of proliferation of the terminally differentiated mammalian
      cardiomyocytes because it is believed that the latter are unable to divide.
      However, proliferation is a necessary step in both processes. Interestingly, the
      small molecule 6-bromoindirubin-3'-oxime (BIO) is the first pharmacological agent
      shown to maintain self-renewal in human and mouse embryonic stem cells. To
      determine whether a molecule that can maintain stem cell properties can also
      participate in controlling the proliferative capability of the highly
      differentiated cardiomyocytes, we examine the effect of BIO in postmitotic
      cardiac cells. Here, we show that BIO promotes proliferation in mammalian
      cardiomyocytes. Our demonstration of a second role for BIO suggests that the
      maintenance of stem cell self-renewal and the induction of proliferation in
      differentiated cardiomyocytes may share common molecular pathways.

PMID- 16984886
TI  - Small-molecule screening identifies the selanazal drug ebselen as a potent
      inhibitor of DMT1-mediated iron uptake.
AB  - HEK293T cells overexpressing divalent metal transporter-1 (DMT1) were established
      to screen for small-molecule inhibitors of iron uptake. Using a fluorescence
      based assay, we tested 2000 known bioactive compounds to find 3 small molecules
      that potently block ferrous iron uptake. One of the inhibitors, ebselen, is a
      seleno compound used in clinical trials as a protective agent against ischemic
      stroke. Ebselen inhibited Fe(II) uptake (IC(50) of approximately 0.22 microM),
      but did not influence Fe(III) transport or DMT1-mediated manganese uptake. An
      unrelated antioxidant, pyrrolidine dithiobarbamate (PDTC), also inhibited DMT1
      activity (IC(50) of approximately 1.54 microM). Both ebselen and PDTC increased
      cellular levels of reduced glutathione. These observations indicate that Fe(II)
      transport by DMT1 can be modulated by cellular redox status and suggest that
      ebselen may act therapeutically to limit iron-catalyzed damage due to transport
      inhibition.

PMID- 16984887
TI  - Quinocarmycin analog DX-52-1 inhibits cell migration and targets radixin,
      disrupting interactions of radixin with actin and CD44.
AB  - In the course of screening for new small-molecule modulators of cell motility, we
      discovered that quinocarmycin (also known as quinocarcin) analog DX-52-1 is an
      inhibitor of epithelial cell migration. While it has been assumed that the main
      target of DX-52-1 is DNA, we identified and confirmed radixin as the relevant
      molecular target of DX-52-1 in the cell. Radixin is a member of the
      ezrin/radixin/moesin family of membrane-actin cytoskeleton linker proteins that
      also participate in signal transduction pathways. DX-52-1 binds specifically and
      covalently to the C-terminal region of radixin, which contains the domain that
      interacts with actin filaments. Overexpression of radixin in cells abrogates
      their sensitivity to DX-52-1's antimigratory activity. Small interfering RNA
      mediated silencing of radixin expression reduces the rate of cell migration.
      Finally, we found that DX-52-1 disrupts radixin's ability to interact with both
      actin and the cell adhesion molecule CD44.

PMID- 16984888
TI  - Structural studies of Vgamma2Vdelta2 T cell phosphoantigens.
AB  - Human gammadelta T cells containing the Vgamma2Vdelta2 (Vgamma9Vdelta2) T cell
      receptor are stimulated by a broad variety of small, phosphorus-containing
      antigenic molecules called phosphoantigens. The structures of several species
      present in both Mycobacteria (TUBags1-4) and in Escherichia coli have been
      reported to contain a formyl-alkyl diphosphate core. Here we report the synthesis
      of the lead member of the series, 3-formyl-1-butyl diphosphate. This compound has
      low activity for gammadelta T cell stimulation, unlike its highly active isomer
      (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate, necessitating a revision of the
      structure of TUBag1. Likewise, the structure of the species identified as the
      pentyl analog (TUBag 2) is revised to 6-phosphogluconate. These results indicate
      that neither TUBag1 nor the m/e 275 species proposed for TUBag2 are 3-formyl-1
      alkyl diphosphates, leading to the conclusion that none of the natural
      phosphoantigens (TUBags1-4) possess the structures reported previously.

PMID- 16984889
TI  - Synthesis and testing of a focused phenothiazine library for binding to HIV-1 TAR
      RNA.
AB  - We have synthesized a series of phenothiazine derivatives, which were used to
      test the structure-activity relationship of binding to HIV-1 TAR RNA. Variations
      from our initial compound, 2-acetylphenothiazine, focused on two moieties: ring
      substitutions and n-alkyl substitutions. Binding characteristics were ascertained
      via NMR, principally by saturation transfer difference spectra of the ligand and
      imino proton resonance shifts of the RNA. Both ring and alkyl substitutions
      manifested NMR changes upon binding. In general, the active site, while somewhat
      flexible, has regions that can be capitalized for increased binding through van
      der Waals interactions and others that can be optimized for solubility in
      subsequent stages of development. However, binding can be nontrivially enhanced
      several-fold through optimization of van der Waals and hydrophilic sites of the
      scaffold.

PMID- 16984891
TI  - Clean-contaminated neck surgery: risk of infection by intrinsic and extrinsic
      factors.
AB  - OBJECTIVE: To evaluate the risk of surgical wound infection (the most common
      complication in neoplastic clean-contaminated neck surgery) due to 10 intrinsic
      risk factors and 5 extrinsic risk factors. DESIGN: Retrospective clinical study.
      SETTING: Academic tertiary referral medical center. PATIENTS: The study group
      included 115 patients with laryngeal carcinomas referred to our department from
      January 1, 1996, to August 31, 2002. INTERVENTION: Fifty-seven patients underwent
      total laryngectomy and 58 underwent subtotal laryngectomy. MAIN OUTCOME MEASURES:
      The association between surgical wound infection due to 10 intrinsic risk factors
      and 5 extrinsic risk factors was evaluated with multivariate models. RESULTS:
      Surgical wound infection occurred in 27 patients (23.5%). There was no
      significant increase in the incidence of infection in patients with extensive
      tumors (P>.20) and in patients undergoing total laryngectomy and subtotal
      laryngectomy (P>.20). The incidence of infection was significantly higher in
      patients with stage IV disease (P<.01), in patients who underwent neck
      dissections (P<.05), and in those presenting with lymph node metastases (P<.001).
      Multivariate analysis showed that the presence of higher tumor stage is the best
      predictor of infection because it is the only significant factor (P<.03) even
      when adjusting for others. The association between infection and the other
      factors considered in this study (age [P>1.0], underweight [P = .26], anemia [P =
      .84], lymphocytopenia [P = .79 by Fisher exact test], number of preoperative
      hospitalizations [P<1.0], preoperative radiotherapy [P = .57 by Fisher exact
      test], diabetes mellitus [P = .70 by Fisher exact test], cirrhosis, resection
      margins infiltrated by the tumor [P = .57 by Fisher exact test], and myocutaneous
      flap reconstructions [P = .82]) was not significant. CONCLUSION: The risk of
      surgical wound infection is correlated with a higher tumor stage and lymph node
      metastases; it is not associated with the extent of surgery or other factors
      considered.

PMID- 16984892
TI  - c-Jun NH2-terminal kinase promotes apoptosis by down-regulating the
      transcriptional co-repressor CtBP.
AB  - Genetic knock out of the transcriptional co-repressor carboxyl-terminal-binding
      protein (CtBP) in mouse embryonic fibroblasts results in up-regulation of several
      genes involved in apoptosis. We predicted, therefore, that a propensity toward
      apoptosis might be regulated through changes in cellular CtBP levels. Previously,
      we have identified the homeodomain-interacting protein kinase 2 as such a
      regulator and demonstrated that HIPK2 activation causes Ser-422 phosphorylation
      and degradation of CtBP. In this study, we found that c-Jun NH2-terminal kinase 1
      activation triggered CtBP phosphorylation on Ser-422 and subsequent degradation,
      inducing p53-independent apoptosis in human lung cancer cells. JNK1 has
      previously been linked to UV-directed apoptosis. Expression of MKK7-JNK1 or
      exposure to UV irradiation reduced cellular levels of CtBP via a proteasome
      mediated pathway. This effect was prevented by JNK1 deficiency. In addition,
      sustained activation of the JNK1 pathway by cisplatin similarly triggered CtBP
      degradation. These findings provide a novel target for chemotherapy in cancers
      lacking p53.

PMID- 16984890
TI  - A chemical and genetic approach to the mode of action of fumagillin.
AB  - Previous mode of action studies identified methionine aminopeptidase 2 (MetAP-2)
      as the target of the antiangiogenic natural product fumagillin and its drug
      candidate analog, TNP-470. We report here that TNP-470-mediated MetAP-2
      inhibition blocks noncanonical Wnt signaling, which plays a critical role in
      development, cell differentiation, and tumorigenesis. Consistent with this
      finding, antisense MetAP-2 morpholino oligonucleotide injection in zebrafish
      embryos phenocopies gastrulation defects seen in noncanonical Wnt5 loss-of
      function zebrafish mutants. MetAP-2 inhibition or depletion blocks signaling
      downstream of the Wnt receptor Frizzled, but upstream of Calmodulin-dependent
      Kinase II, RhoA, and c-Jun N-terminal Kinase. Moreover, we demonstrate that TNP
      470 does not block the canonical Wnt/beta-catenin pathway. Thus, TNP-470
      selectively regulates noncanonical over canonical Wnt signaling and provides a
      unique means to explore and dissect the biological systems mediated by these
      pathways.

PMID- 16984893
TI  - Hierarchical and multi-resolution representation of protein flexibility.
AB  - MOTIVATION: Conformational rearrangements during molecular interactions are
      observed in a wide range of biological systems. However, computational methods
      that aim at simulating and predicting molecular interactions are still largely
      ignoring the flexible nature of biological macromolecules as the number of
      degrees of freedom is computationally intractable when using brute force
      representations. RESULTS: In this article, we present a computational data
      structure called the Flexibility Tree (FT) that enables a multi-resolution and
      hierarchical encoding of molecular flexibility. This tree-like data structure
      allows the encoding of relatively small, yet complex sub-spaces of a protein's
      conformational space. These conformational sub-spaces are parameterized by a
      small number of variables and can be searched efficiently using standard global
      search techniques. The FT structure makes it straightforward to combine and nest
      a wide variety of motion types such as hinge, shear, twist, screw, rotameric side
      chains, normal modes and essential dynamics. Moreover, the ability to assign
      shapes to the nodes in a FT allows the interactive manipulation of flexible
      protein shapes and the interactive visualization of the impact of conformational
      changes on the protein's overall shape. We describe the design of the FT and
      illustrate the construction of such trees to hierarchically combine motion
      information obtained from a variety of sources ranging from experiment to user
      intuition, and describing conformational changes at different biological scales.
      We show that the combination of various types of motion helps refine the encoded
      conformational sub-spaces to include experimentally determined structures, and we
      demonstrate searching these sub-spaces for specific conformations.

PMID- 16984894
TI  - Donor funding priorities for communicable disease control in the developing
      world.
AB  - Prior research has considered donor funding for developing world health by
      recipient and donor country but not by disease. Examining funding by disease is
      critical since diseases may be in competition with one another for priority and
      donors may be making allocation decisions in ways that do not correspond to
      developing world need. In this study I calculate donor funding for 20
      historically high-burden communicable diseases for the years 1996 to 2003 and
      examine factors that may explain variance in priority levels among diseases. I
      consider funding for developing world health from 42 major donors, classifying
      grants according to the communicable disease targeted. Data show that funding
      does not correspond closely with burden. Acute respiratory infections comprise
      more than a quarter of the burden among these diseases but receive less than 3%
      of direct aid. Malaria also stands out as a high-burden neglected disease. The
      evidence indicates that neither developing world need nor industrialized world
      interests explain all funding patterns, and that donors may be imitating one
      another in ways that do not take into account problems in the developing world.
      There is an urgent need for a major increase in funding for communicable disease
      control in the developing world, and for more balanced allocation of the
      resources already provided.

PMID- 16984895
TI  - A proposed adaptation of the EFQM fundamental concepts of excellence to health
      care based on the PATH framework.
AB  - OBJECTIVE: The use of the European Foundation for Quality Management (EFQM) Model
      in health care has found that this model is useful in promoting quality
      improvement, but its use in health care organizations is challenging because
      being a generic model, it does not cover the clinical aspects or the specifics of
      this field. For that reason, this article aims to bring the EFQM fundamental
      concepts of excellence closer to health care, using a specific model as a
      reference to this field: the Performance Assessment Tool for quality improvement
      in Hospitals (PATH) conceptual framework, developed by the WHO Regional Office
      for Europe. METHOD: A content analysis was performed to independently identify
      the contents that defined the elements of both frameworks. Then, using defined
      criteria, two independent researchers compared the contents of the elements of
      both frameworks. The elements from both frameworks that were equivalent were
      aggregated. Several experts discussed the aspects with discrepancies between the
      two comparisons. Finally, the EFQM framework is adapted to health care by adding
      to those aggregated elements the aspects that were exclusive from one of the
      models. RESULTS: The EFQM framework has many correspondences to a health care
      specific framework. The EFQM-health care-adapted framework has eight quality
      dimensions, two of them (customer focus and safety) being overlapped with the
      other six (staff, results orientation, responsive governance, leadership and
      constancy of purpose, clinical effectiveness, and partnership development). This
      model also has two methodological dimensions (management by processes and facts
      and continuous learning; improvement and innovation). CONCLUSION: This adapted
      model seems useful for health care organizations, but it needs to be further used
      to corroborate this preliminary finding.

PMID- 16984896
TI  - Development of an algorithm for TLD badge system for dosimetry in the field of X
      and gamma radiation in terms of Hp(10).
AB  - In view of the introduction of International Commission on Radiation Units and
      Measurements operational quantities Hp(10) and Hp(0.07), defined for individual
      monitoring, it became necessary to develop an algorithm that gives direct
      response of the dosemeter in terms of the operational quantities. Hence, for this
      purpose and also to improve the accuracy in dose estimation especially in the
      mixed fields of X ray and gamma, an algorithm was developed based on higher-order
      polynomial fit of the data points generated from the dose-response of discs under
      different filter regions of the present TL dosemeter system for known delivered
      doses. Study on the response of the BARC TL dosemeter system based on CaSO(4):Dy
      Teflon thermoluminescence dosemeter discs in the mixed fields of X and gamma
      radiation was carried out to ensure that the accuracies are within the prescribed
      limits recommended by the international organisations. The prevalent algorithm,
      based on the ratios of the disc response under various filters regions of the
      dosemeter to pure photons, was tested for different proportion of two radiations
      in case of mixed field dosimetry. It was found that the accuracy for few fields
      is beyond the acceptable limit in case of prevalent algorithm. The new proposed
      algorithm was also tested in mixed fields of photon fields and to pure photon
      fields of varied angles. It was found that the response of the dosemeter in mixed
      fields of photons and its angular response are satisfactory. The new algorithm
      can be used to record and report the personal dose in terms of Hp(10) as per the
      international recommendation for the present TL dosemeter.

PMID- 16984897
TI  - In vivo selection during ofloxacin therapy of Escherichia coli with combined
      topoisomerase mutations that confer high resistance to ofloxacin but
      susceptibility to nalidixic acid.
AB  - OBJECTIVES: To investigate quinolone resistance mechanisms in an Escherichia coli
      clinical isolate (Ar2) resistant to ofloxacin but susceptible to nalidixic acid
      selected after 10 days of ofloxacin therapy in a patient with prostatitis.
      METHODS: Molecular typing (ERIC-PCR and RAPD), antibiotic susceptibility and
      gyrA, gyrB, parC and parE QRDR sequences were compared for E. coli Ar2 and a wild
      type E. coli (Ar1) isolated 2 months earlier in the same patient. Ofloxacin
      resistant mutants were selected in vitro in order to reproduce the mutations
      observed and the original phenotype. RESULTS: The two strains were similar with
      regard to antibiotic susceptibility except quinolones and for ERIC-PCR and RAPD
      patterns, suggesting a clonal relationship and acquisition of quinolone
      resistance by chromosomal mutation. Quinolone MICs were 3, 0.12, 0.05 and 0.02
      mg/L of nalidixic acid, ofloxacin, levofloxacin and ciprofloxacin, respectively,
      for E. coli Ar1 and 6, 32, 8 and 1 mg/L, respectively, for E. coli Ar2. The
      strain Ar2 harboured two substitutions, Gly-81-->Asp in GyrA and Ser-80-->Arg in
      ParC. Introduction into E. coli Ar2 of the wild-type gyrA fully complemented
      fluoroquinolone resistance. Although the strain was not a hypermutator, ofloxacin
      first-step resistant mutants with gyrA mutations were easily obtained from E.
      coli Ar1 and 25% of them were at codon 81. In vitro stepwise combination of Gly
      81-->Asp in GyrA and Ser-80-->Arg in ParC reproduced the original phenotype in E.
      coli KL16. CONCLUSIONS: A double topoisomerase mutant was selected in vivo by 10
      days ofloxacin. The mutations were originally combined for a result of ofloxacin
      resistance but nalidixic acid susceptibility.

PMID- 16984898
TI  - Influence of atazanavir 200 mg on the intracellular and plasma pharmacokinetics
      of saquinavir and ritonavir 1600/100 mg administered once daily in HIV-infected
      patients.
AB  - OBJECTIVES: To examine cellular and plasma concentrations of atazanavir when
      given in combination with saquinavir/ritonavir in HIV+ patients. METHODS: Twelve
      HIV+ patients were receiving saquinavir/atazanavir/ritonavir 1600/200/100 mg once
      daily and venous blood samples were taken to determine cellular and plasma
      concentrations of each protease inhibitor at 2, 6, 12 and 24 h. Peripheral blood
      mononuclear cells were separated by density gradient centrifugation. The ratio of
      the cellular AUC0-24/plasma AUC0-24 was calculated to determine cellular drug
      accumulation. Lymphocyte P-glycoprotein (P-gp), breast cancer resistance protein
      (BCRP) and multidrug resistance-associated protein (MRP1) expression was
      determined by flow cytometry. Nine of the patients had previously received a
      regimen of saquinavir/ritonavir 1600/100 mg; therefore the effect of atazanavir
      on the cellular and plasma pharmacokinetics of saquinavir and ritonavir was
      examined. RESULTS: In vivo cellular and plasma determinations of saquinavir,
      atazanavir and ritonavir gave accumulation ratios of 4.9, 1.2 and 1.7,
      respectively. There was no relationship between saquinavir, atazanavir or
      ritonavir accumulation and P-gp, MRP1 or BCRP expression. When comparing
      pharmacokinetic values in the nine patients receiving saquinavir/ritonavir with
      and without atazanavir, the median cellular saquinavir AUC0-24 was significantly
      increased (34.9-117.2 mg.h/L) on addition of atazanavir (P=0.004). The C24 of
      saquinavir in plasma and cells was significantly higher with atazanavir (plasma
      C24 0.05 versus 0.14 mg/L with atazanavir; cellular C24 0.61 versus 2.03 mg/L
      with atazanavir, P=0.02). CONCLUSIONS: The mechanism of differential
      intracellular protease inhibitor accumulation is unclear. Co-administration of
      atazanavir caused an increase in both the plasma and cellular exposure (AUC0-24)
      and C24 of saquinavir but not ritonavir.

PMID- 16984899
TI  - Functions of the left superior frontal gyrus in humans: a lesion study.
AB  - The superior frontal gyrus (SFG) is thought to contribute to higher cognitive
      functions and particularly to working memory (WM), although the nature of its
      involvement remains a matter of debate. To resolve this issue, methodological
      tools such as lesion studies are needed to complement the functional imaging
      approach. We have conducted the first lesion study to investigate the role of the
      SFG in WM and address the following questions: do lesions of the SFG impair WM
      and, if so, what is the nature of the WM impairment? To answer these questions,
      we compared the performance of eight patients with a left prefrontal lesion
      restricted to the SFG with that of a group of 11 healthy control subjects and two
      groups of patients with focal brain lesions [prefrontal lesions sparing the SFG
      (n = 5) and right parietal lesions (n = 4)] in a series of WM tasks. The WM tasks
      (derived from the classical n-back paradigm) allowed us to study the impact of
      the SFG lesions on domain (verbal, spatial, face) and complexity (1-, 2- and 3
      back) processing within WM. As expected, patients with a left SFG lesion
      exhibited a WM deficit when compared with all control groups, and the impairment
      increased with the complexity of the tasks. This complexity effect was
      significantly more marked for the spatial domain. Voxel-to-voxel mapping of each
      subject's performance showed that the lateral and posterior portion of the SFG
      (mostly Brodmann area 8, rostral to the frontal eye field) was the subregion that
      contributed the most to the WM impairment. These data led us to conclude that (i)
      the lateral and posterior portion of the left SFG is a key component of the
      neural network of WM; (ii) the participation of this region in WM is triggered by
      the highest level of executive processing; (iii) the left SFG is also involved in
      spatially oriented processing. Our findings support a hybrid model of the
      anatomical and functional organization of the lateral SFG for WM, according to
      which this region is involved in higher levels of WM processing (monitoring and
      manipulation) but remains oriented towards spatial cognition, although the domain
      specificity is not exclusive and is overridden by an increase in executive
      demand, regardless of the domain being processed. From a clinical perspective,
      this study provides new information on the impact of left SFG lesions on
      cognition that will be of use to neurologists and neurosurgeons.

PMID- 16984900
TI  - Autoimmunity to GABAA-receptor-associated protein in stiff-person syndrome.
AB  - Stiff-person syndrome (SPS) is an autoimmune neurological disorder characterized
      by autoantibodies to glutamic acid decarboxylase (GAD), the enzyme responsible
      for the synthesis of inhibitory neurotransmitter GABA. To search for biomarkers
      that distinguish SPS from other neurological disorders (OND), we used surface
      enhanced laser desorption/ionization-time of flight (SELDI-TOF) mass spectrometry
      to obtain proteomic profile of sera from 25 GAD-positive SPS patients and 25
      controls. A significant decrease was found in the level of a protein
      corresponding to GABA(A)-receptor-associated protein (GABARAP), which is
      responsible for the stability and surface expression of the GABA(A)-receptor. Up
      to 70% of the SPS sera examined, compared with 10% of the controls,
      immunoprecipitated GABARAP protein. Antibodies raised against GABARAP
      immunostained neuronal cell bodies as well as axonal and dendritic processes, as
      visualized by confocal microscopy. In vitro experiments demonstrated that the IgG
      from GABARAP antibody-positive patients, but not control IgG, significantly
      inhibited the surface expression of GABA(A)-receptor. We conclude that GABARAP is
      a new autoantigen in SPS. Because the patients' IgG inhibits the expression of
      GABA(A)-receptors, the circulating antibodies could impair GABAergic pathways and
      play a role in the clinical symptomatology of SPS patients.

PMID- 16984901
TI  - Pathological consequences of VCP mutations on human striated muscle.
AB  - Mutations in the valosin-containing protein (VCP, p97) gene on chromosome 9p13
      p12 cause a late-onset form of autosomal dominant inclusion body myopathy
      associated with Paget disease of the bone and frontotemporal dementia (IBMPFD).
      We report on the pathological consequences of three heterozygous VCP (R93C,
      R155H, R155C) mutations on human striated muscle. IBMPFD skeletal muscle
      pathology is characterized by degenerative changes and filamentous VCP- and
      ubiquitin-positive cytoplasmic and nuclear protein aggregates. Furthermore, this
      is the first report demonstrating that mutant VCP leads to a novel form of
      dilatative cardiomyopathy with inclusion bodies. In contrast to post-mitotic
      striated muscle cells and neurons of IBMPFD patients, evidence of protein
      aggregate pathology was not detected in primary IBMPFD myoblasts or in transient
      and stable transfected cells using wild-type-VCP and R93C-, R155H-, R155C-VCP
      mutants. Glutathione S-transferase pull-down experiments showed that all three
      VCP mutations do not affect the binding to Ufd1, Npl4 and ataxin-3. Structural
      analysis demonstrated that R93 and R155 are both surface-accessible residues
      located in the centre of cavities that may enable ligand-binding. Mutations at
      R93 and R155 are predicted to induce changes in the tertiary structure of the VCP
      protein. The search for putative ligands to the R93 and R155 cavities resulted in
      the identification of cyclic sugar compounds with high binding scores. The latter
      findings provide a novel link to VCP carbohydrate interactions in the complex
      pathology of IBMPFD.

PMID- 16984902
TI  - Subcortical visual dysfunction in schizophrenia drives secondary cortical
      impairments.
AB  - Visual processing deficits are an integral component of schizophrenia and are
      sensitive predictors of schizophrenic decompensation in healthy adults. The
      primate visual system consists of discrete subcortical magnocellular and
      parvocellular pathways, which project preferentially to dorsal and ventral
      cortical streams. Subcortical systems show differential stimulus sensitivity,
      while cortical systems, in turn, can be differentiated using surface potential
      analysis. The present study examined contributions of subcortical dysfunction to
      cortical processing deficits using high-density event-related potentials. Event
      related potentials were recorded to stimuli biased towards the magnocellular
      system using low-contrast isolated checks in Experiment 1 and towards the
      magnocellular or parvocellular system using low versus high spatial frequency
      (HSF) sinusoidal gratings, respectively, in Experiment 2. The sample consisted of
      23 patients with schizophrenia or schizoaffective disorder and 19 non-psychiatric
      volunteers of similar age. In Experiment 1, a large decrease in the P1 component
      of the visual event-related potential in response to magnocellular-biased
      isolated check stimuli was seen in patients compared with controls (F = 13.2, P =
      0.001). Patients also showed decreased slope of the contrast response function
      over the magnocellular-selective contrast range compared with controls (t = 9.2,
      P = 0.04) indicating decreased signal amplification. In Experiment 2, C1 (F =
      8.5, P = 0.007), P1 (F = 33.1, P < 0.001) and N1 (F = 60.8, P < 0.001) were
      reduced in amplitude to magnocellular-biased low spatial frequency (LSF) stimuli
      in patients with schizophrenia, but were intact to parvocellular-biased HSF
      stimuli, regardless of generator location. Source waveforms derived from inverse
      dipole modelling showed reduced P1 in Experiment 1 and reduced C1, P1 and N1 to
      LSF stimuli in Experiment 2, consistent with surface waveforms. These results
      indicate pervasive magnocellular dysfunction at the subcortical level that leads
      to secondary impairment in activation of cortical visual structures within dorsal
      and ventral stream visual pathways. Our finding of early visual dysfunction is
      consistent with and explanatory of classic literature showing subjective
      complaints of visual distortions and is consistent with early visual processing
      deficits reported in schizophrenia. Although deficits in visual processing have
      frequently been construed as resulting from failures of top-down processing, the
      present findings argue strongly for bottom-up rather than top-down dysfunction at
      least within the early visual pathway. Deficits in magnocellular processing in
      this task may reflect more general impairments in neuronal systems functioning,
      such as deficits in non-linear amplification and may thus represent an organizing
      principle for predicting neurocognitive dysfunction in schizophrenia.

PMID- 16984904
TI  - Sixty years on: the price of assembling military gas masks in 1940.
AB  - BACKGROUND: Between 1940 and 1944 military gas masks with filter pads containing
      20% crocidolite were assembled in a Nottingham factory. METHODS: Records supplied
      by the late Professor Stephen Jones were of 1154 persons, mainly women, who had
      worked in the factory during this period; they included many deaths from
      mesothelioma. A systematic effort was therefore made to establish causes of death
      for the whole cohort. RESULTS: Of 640 employees with full name and sex recorded,
      567 (89%) were traced. Of these, 491 had died, including 65 from mesothelioma,
      though only 54 were certified as such. After exclusion of these 54, standardised
      mortality ratios were significantly raised for respiratory cancer (SMR 2.5) and
      carcinomatosis (SMR 3.2). The pattern of mortality in the remaining 514 employees
      without full identification was similar, but a low tracing rate (40%) did not
      justify their further analysis. The first death from mesothelioma was in 1963 (22
      years after first exposure) and the last in 1994, whereas a further 5.0 cases
      would have been expected between 1996 and 2003 (p = 0.0065). CONCLUSION: These
      findings in a cohort followed over 60 years after brief exposure to crocidolite
      confirm a high and specific risk of mesothelioma (28% peritoneal) and perhaps of
      lung cancer some 20-50 years later. The statistically significant absence of
      further mesothelioma cases during the past eight years suggests that crocidolite,
      though durable, is slowly removed.

PMID- 16984903
TI  - Role of toll-like receptor signalling in Abeta uptake and clearance.
AB  - Deposits of amyloid beta-protein (Abeta) in neuritic plaques and cerebral vessels
      are a pathological hallmark of Alzheimer's disease. Fibrillar Abeta deposits are
      closely associated with inflammatory responses such as activated microglia in
      brain with this disease. Increasing lines of evidence support the hypothesis that
      activated microglia, innate immune cells in the CNS, play a pivotal role in the
      progression of the disease: either clearing Abeta deposits by phagocytic activity
      or releasing cytotoxic substances and pro-inflammatory cytokines. Toll-like
      receptors (TLRs) are a family of pattern-recognition receptors in the innate
      immune system. Exogenous and endogenous TLR ligands activate microglia. To
      investigate the role of TLR4 in the amyloidogenesis in vivo, we determined the
      amounts of cerebral Abeta in Alzheimer's disease mouse models with different
      genotypes of TLR4 using three distinct methods. We show that mouse models (Mo/Hu
      APPswe PS1dE9 mice) homozygous for a destructive mutation of TLR4 (Tlr(Lps
      d)/Tlr(Lps-d)) had increases in diffuse and fibrillar Abeta deposits by
      immunocytochemistry, fibrillar Abeta deposits by thioflavine-S staining and
      buffer-soluble and insoluble Abeta by ELISA in the cerebrum, as compared with
      TLR4 wild-type mouse models. Although the differences in these parameters were
      less significant, mouse models heterozygous for the mutation (Tlr(Lps-d)/) showed
      co-dominant phenotypes. Consistent with these observations in vivo, cultured
      microglia derived from Tlr(Lps-d)/Tlr(Lps-d) mice failed to show an increase in
      Abeta uptake after stimulation with a TLR4 ligand but not with a TLR9 ligand in
      vitro. Furthermore, activation of microglia (BV-2 cell) with a TLR2, TLR4 or TLR9
      ligand, markedly boosted ingestion of Abeta in vitro. These results suggest that
      TLR signalling pathway(s) may be involved in clearance of Abeta-deposits in the
      brain and that TLRs can be a therapeutic target for Alzheimer's disease.

PMID- 16984905
TI  - Enzymatically active N-deacetylase/N-sulfotransferase-2 is present in liver but
      does not contribute to heparan sulfate N-sulfation.
AB  - Heparan sulfate (HS) proteoglycans influence embryonic development through
      interactions with growth factors and morphogens. The interactions depend on HS
      structure, which is largely determined during biosynthesis by Golgi enzymes. NDST
      (glucosaminyl N-deacetylase/N-sulfotransferase), responsible for HS N-sulfation,
      is a key enzyme directing further modifications including O-sulfation. To
      elucidate the roles of the different NDST isoforms in HS biosynthesis, we took
      advantage of mice with targeted mutations in NDST1 and NDST2 and used liver as
      our model organ. Of the four NDST isoforms, only NDST1 and NDST2 transcripts were
      shown to be expressed in control liver. The absence of NDST1 or NDST2 in the
      knock-out mice did not affect transcript levels of other NDST isoforms or other
      HS modification enzymes. Although the sulfation level of HS synthesized in NDST1
      /- mice was drastically lowered, liver HS from wild-type mice, from NDST1+/-,
      NDST2-/-, and NDST1+/- / NDST2-/- mice all had the same structure despite greatly
      reduced NDST enzyme activity (30% of control levels in NDST1+/- / NDST2-/-
      embryonic day 18.5 embryos). Enzymatically active NDST2 was shown to be present
      in similar amounts in wild-type, NDST1-/-, and NDST1+/- embryonic day 18.5 liver.
      Despite the substantial contribution of NDST2 to total NDST enzyme activity in
      embryonic day 18.5 liver (approximately 40%), its presence did not appear to
      affect HS structure as long as NDST1 was also present. In NDST1-/- embryonic day
      18.5 liver, in contrast, NDST2 was responsible for N-sulfation of the low
      sulfated HS. A tentative model to explain these results is presented.

PMID- 16984906
TI  - Melanin and Glycera jaws: emerging dark side of a robust biocomposite structure.
AB  - Defining the design principles guiding the fabrication of superior biocomposite
      structures from an assemblage of ordinary molecules is a key goal of biomimetics.
      Considering their low degree of mineralization, Glycera jaws have been shown to
      be extraordinarily resistant to abrasion based on the metric hardness3/Young's
      modulus2. The jaws also exhibit an impressive chemical inertness withstanding
      boiling concentrated hydrochloric acid as well as boiling concentrated sodium
      hydroxide. A major organic component largely responsible for the chemical
      inertness of the jaws has been characterized using a spectrophotometric assay for
      melanin content, 13C solid state nuclear magnetic resonance, IR spectroscopy, and
      laser desorption ionization-time of flight mass spectrometry and is identified
      here as a melanin-like network. Although melanin is widely distributed as a
      pigment in tissues and other structural biomaterials, to our knowledge, Glycera
      jaws represent the first known integument to exploit melanin as a cohesive load-
      and shape-bearing material.

PMID- 16984907
TI  - ATP-binding cassette transporter A1 expression disrupts raft membrane
      microdomains through its ATPase-related functions.
AB  - ATP-binding cassette transporter A1 (ABCA1) is known to mediate cholesterol
      efflux to lipid-poor apolipoprotein A-I. In addition, ABCA1 has been shown to
      influence functions of the plasma membrane, such as endocytosis and phagocytosis.
      Here, we report that ABCA1 expression results in a significant redistribution of
      cholesterol and sphingomyelin from rafts to non-rafts. Caveolin, a raft/caveolae
      marker also redistributes from punctate caveolae-like structures to the general
      area of the plasma membrane upon ABCA1 expression. Furthermore, we observed
      significant reduction of Akt activation in ABCA1-expressing cells, consistent
      with raft disruption. Cholesterol content in the plasma membrane is, however, not
      altered. Moreover, we provide evidence that a non-functional ABCA1 with mutation
      in an ATP-binding domain, A937V, fails to redistribute cholesterol,
      sphingomyelin, or caveolin. A937V also fails to influence Akt activation.
      Finally, we show that apolipoprotein A-I preferentially associates with non-raft
      membranes in ABCA1-expressing cells. Our results thus demonstrate that ABCA1
      causes a change in overall lipid packing of the plasma membrane, likely through
      its ATPase-related functions. Such reorganization by ABCA1 effectively expands
      the non-raft membrane fractions and, consequentially, pre-conditions cells for
      cholesterol efflux.

PMID- 16984908
TI  - Nitrite reductase activity of sol-gel-encapsulated deoxyhemoglobin. Influence of
      quaternary and tertiary structure.
AB  - Nitrite reductase activity of deoxyhemoglobin (HbA) in the red blood cell has
      been proposed as a non-nitric-oxide synthase source of deliverable nitric oxide
      (NO) within the vasculature. An essential element in this scheme is the
      dependence of this reaction on the quaternary/tertiary structure of HbA. In the
      present work sol-gel encapsulation is used to trap and stabilize deoxy-HbA in
      either the T or R quaternary state, thus allowing for the clear-cut monitoring of
      nitrite reductase activity as a function of quaternary state with and without
      effectors. The results indicate that reaction is not only R-T-dependent but also
      heterotropic effector-dependent within a given quaternary state. The use of the
      maximum entropy method to analyze carbon monoxide (CO) recombination kinetics
      from fully and partially liganded sol-gel-encapsulated T-state species provides a
      framework for understanding effector modulation of T-state reactivity by
      influencing the distribution of high and low reactivity T-state conformations.

PMID- 16984910
TI  - The structure, location, and function of perlecan, a prominent pericellular
      proteoglycan of fetal, postnatal, and mature hyaline cartilages.
AB  - The aim of this study was to immunolocalize perlecan in human fetal, postnatal,
      and mature hyaline cartilages and to determine information on the structure and
      function of chondrocyte perlecan. Perlecan is a prominent component of human
      fetal (12-14 week) finger, toe, knee, and elbow cartilages; it was localized
      diffusely in the interterritorial extracellular matrix, densely in the
      pericellular matrix around chondrocytes, and to small blood vessels in the joint
      capsules and perichondrium. Aggrecan had a more intense distribution in the
      marginal regions of the joint rudiments and in para-articular structures.
      Perlecan also had a strong pericellular localization pattern in postnatal (2-7
      month) and mature (55-64 year) femoral cartilages, whereas aggrecan had a
      prominent extracellular matrix distribution in these tissues. Western blotting
      identified multiple perlecan core protein species in extracts of the postnatal
      and mature cartilages, some of which were substituted with heparan sulfate and/or
      chondroitin sulfate and some were devoid of glycosaminoglycan substitution. Some
      perlecan core proteins were smaller than intact perlecan, suggesting that
      proteolytic processing or alternative splicing had occurred. Surface plasmon
      resonance and quartz crystal microbalance with dissipation experiments
      demonstrated that chondrocyte perlecan bound fibroblast growth factor (FGF)-1 and
      -9 less efficiently than endothelial cell perlecan. The latter perlecan supported
      the proliferation of Baf-32 cells transfected with FGFR3c equally well with FGF-1
      and -9, whereas chondrocyte perlecan only supported Baf-32 cell proliferation
      with FGF-9. The function of perlecan therefore may not be universal but may vary
      with its cellular origin and presumably its structure.

PMID- 16984909
TI  - Molecular mechanism of membrane docking by the Vam7p PX domain.
AB  - The Vam7p t-SNARE is an essential component of the vacuole fusion machinery that
      mediates membrane trafficking and protein sorting in yeast. Vam7p is recruited to
      vacuoles by its N-terminal PX domain that specifically recognizes PtdIns(3)P in
      the bilayers, however the precise mechanism of membrane anchoring remains
      unclear. Here we describe a molecular basis for membrane targeting and
      penetration by the Vam7p PX domain based on structural and quantitative analysis
      of its interactions with lipids and micelles. Our results derived from in vitro
      binding measurements using NMR, monolayer surface tension experiments and
      mutagenesis reveal a multivalent membrane docking mechanism involving specific
      PtdIns(3)P recognition that is facilitated by electrostatic interactions and
      accompanying hydrophobic insertion. Both the hydrophobic and electrostatic
      components enhance the Vam7p PX domain association with PtdIns(3)P-containing
      membranes. The inserting Val(70), Leu(71), and Trp(75) residues located next to
      the PtdIns(3)P binding pocket are surrounded by a basic patch, which is involved
      in nonspecific electrostatic contacts with acidic lipids, such as PtdSer.
      Substitution of the insertion residues significantly reduces the binding and
      penetrating power of the Vam7p PX domain and leads to cytoplasmic redistribution
      of the EGFP-tagged protein. The affinities of the PX domain for PtdIns(3)P and
      other lipids reveal a remarkable synergy within the multivalent complex that
      stably anchors Vam7p at the vacuolar membrane.

PMID- 16984911
TI  - Identification of precise electrostatic recognition sites between cytochrome c6
      and the photosystem I subunit PsaF using mass spectrometry.
AB  - The reduction of the photo-oxidized special chlorophyll pair P700 of photosystem
      I (PSI) in the photosynthetic electron transport chain of eukaryotic organisms is
      facilitated by the soluble copper-containing protein plastocyanin (pc). In the
      absence of copper, pc is functionally replaced by the heme-containing protein
      cytochrome c6 (cyt c6) in the green alga Chlamydomonas reinhardtii. Binding and
      electron transfer between both donors and PSI follows a two-step mechanism that
      depends on electrostatic and hydrophobic recognition between the partners.
      Although the electrostatic and hydrophobic recognition sites on pc and PSI are
      well known, the precise electrostatic recognition site on cyt c6 is unknown. To
      specify the interaction sites on a molecular level, we cross-linked cyt c6 and
      PSI using a zero-length cross-linker and obtained a cross-linked complex
      competent in fast and efficient electron transfer. As shown previously, cyt c6
      cross-links specifically with the PsaF subunit of PSI. Mass spectrometric
      analysis of tryptic peptides from the cross-linked product revealed specific
      interaction sites between residues Lys27 of PsaF and Glu69 of cyt c6 and between
      Lys23 of PsaF and Glu69/Glu70 of cyt c6. Using these new data, we present a
      molecular model of the intermolecular electron transfer complex between
      eukaryotic cyt c6 and PSI.

PMID- 16984912
TI  - The SL1-SL2 (stem-loop) domain is the primary determinant for stability of the
      gamma retroviral genomic RNA dimer.
AB  - Retroviral genomes are assembled from two sense-strand RNAs by noncovalent
      interactions at their 5' ends, forming a dimer. The RNA dimerization domain is a
      potential target for antiretroviral therapy and represents a compelling RNA
      folding problem. The fundamental dimerization unit for the Moloney murine sarcoma
      gamma retrovirus spans a 170-nucleotide minimal dimerization active sequence. In
      the dimer, two self-complementary sequences, PAL1 and PAL2, form intermolecular
      duplexes, and an SL1-SL2 (stem-loop) domain forms loop-loop base pairs, mediated
      by GACG tetraloops, and extensive tertiary interactions. To develop a framework
      for assembly of the retroviral RNA dimer, we quantified the stability of and
      established nucleotide resolution secondary structure models for sequence
      variants in which each motif was compromised. Base pairing and tertiary
      interactions between SL1-SL2 domains contribute a large free energy increment of 
      10 kcal/mol. In contrast, even though the PAL1 and PAL2 intermolecular duplexes
      span 10 and 16 bp in the dimer, respectively, they contribute only -2.5 kcal/mol
      to stability, roughly equal to a single new base pair. First, these results
      emphasize that the energetic costs for disrupting interactions in the monomer
      state nearly balance the PAL1 and PAL2 base pairing interactions that form in the
      dimer. Second, intermolecular duplex formation plays a biological role distinct
      from simply stabilizing the structure of the retroviral genomic RNA dimer.

PMID- 16984913
TI  - Identification of an AHNAK binding motif specific for the Annexin2/S100A10
      tetramer.
AB  - The Annexin2 tetramer (A2t), which consists of two Annexin2 molecules bound to a
      S100A10 dimer, is implicated in membrane-trafficking events. Here, we showed
      using a yeast triple-hybrid experiment and in vitro binding assay that Annexin2
      is required for strong binding of S100A10 to the C-terminal domain of the protein
      Ahnak. We also revealed that this effect involves only the Annexin2 N-terminal
      tail, which is implicated in S100A10/Annexin2 tetramerization. The minimal A2t
      binding motif (A2tBP1) in Ahnak was mapped to a 20-amino acid peptide, and this
      peptide is highly specific for A2t. We also identified a second A2t binding motif
      (A2tBP2) present in the N-terminal domain of Ahnak, which binds to A2t, albeit
      with less affinity. When overexpressed as an EGFP fusion protein in MDCK cells,
      A2tBPs cofractionate in a calcium-dependent manner and co-immunoprecipitate with
      S100A10 and Annexin2. In living cells, A2tBPs target EGFP to the cytoplasm as
      does Annexin2. In response to oxidative and mechanical stress, EGFP-A2tBPs
      relocalize within minutes to the plasma membrane; a behavior shared with Annexin2
      GFP. These results suggest that the A2t complex exists within the cytoplasm of
      resting living cells and that its localization at the plasma membrane relies on
      cellular signaling. Together, our data demonstrate that A2tBP1 is a specific A2t
      complex binding domain and may be a powerful tool to help elucidate A2t structure
      and cellular functions.

PMID- 16984914
TI  - Phospholipid dependence and liposome reconstitution of purified hyaluronan
      synthase.
AB  - Previous radiation inactivation and enzyme characterization studies demonstrated
      that the Streptococcus equisimilis hyaluronan synthase (seHAS) is phospholipid
      dependent and that cardiolipin (CL) is the best phospholipid for enzyme
      activation. Here we investigated the ability of seHAS, purified in the absence of
      added lipid, to be activated by synthetic phosphatidic acid (PA),
      phosphatidylserine, or CL lipids containing fatty acyl chains of different length
      or different numbers of double bonds. The most effective lipid was tetraoleoyl CL
      (TO-CL), whereas tetramyristoyl CL (TM-CL) was ineffective. None of the
      phosphatidylserine species tested gave significant activation. PAs containing C10
      to C18 saturated acyl chains were not effective activators, and neither were
      oleoyl lyso PA, dilinoleoyl PA, or PA containing one oleoyl chain and either a
      palmitoyl or stearoyl chain. In contrast, dioleoyl PA stimulated seHAS
      approximately 10-fold, to approximately 20% of the activity observed with TO-CL.
      The tested acidic lipids such as PA and CL activated the enzyme most efficiently
      if they contained only oleic acid. Mixing experiments showed that the enzyme
      interacts preferentially with TO-CL in the presence of TM-CL. Similarly, seHAS
      incorporated into phosphotidylcholine-based liposomes showed increasing activity
      with increasing TO-CL, but not TM-CL, content. Inactivation of membrane-bound
      seHAS by solubilization with Nonidet P-40 was prevented by TO-CL, but not TM-CL.
      The pH dependence of seHAS in the presence of synthetic or naturally occurring
      CLs showed the same pattern of lipid preference between pH 6 and 10.5.
      Unexpectedly, HAS showed lipid-independent activity at pH 11.5. The results
      suggest that Class I HAS enzymes are lipid-dependent and that assembly of active
      seHAS-lipid complexes has high specificity for the phospholipid head group and
      the nature of the fatty acyl chains.

PMID- 16984915
TI  - Requirement for annexin A1 in plasma membrane repair.
AB  - Ca2+ entering a cell through a torn or disrupted plasma membrane rapidly triggers
      a combination of homotypic and exocytotic membrane fusion events. These events
      serve to erect a reparative membrane patch and then anneal it to the defect site.
      Annexin A1 is a cytosolic protein that, when activated by micromolar Ca2+, binds
      to membrane phospholipids, promoting membrane aggregation and fusion. We
      demonstrate here that an annexin A1 function-blocking antibody, a small peptide
      competitor, and a dominant-negative annexin A1 mutant protein incapable of Ca2+
      binding all inhibit resealing. Moreover, we show that, coincident with a
      resealing event, annexin A1 becomes concentrated at disruption sites. We propose
      that Ca2+ entering through a disruption locally induces annexin A1 binding to
      membranes, initiating emergency fusion events whenever and wherever required.

PMID- 16984916
TI  - VP1686, a Vibrio type III secretion protein, induces toll-like receptor
      independent apoptosis in macrophage through NF-kappaB inhibition.
AB  - Vibrio parahaemolyticus, causative agent of human gastrointestinal diseases,
      possesses several virulent machineries including thermostable direct hemolysin
      and type III secretion systems (TTSS1 and -2). In this report, we establish that
      TTSS1-dependent secretion and translocation of a V. parahaemolyticus effector
      protein VP1686 into the cytosol induces DNA fragmentation in macrophages. We
      performed yeast two-hybrid screening to identify the molecules involved in VP1686
      mediated cell death pathways and showed that nuclear factor RelA p65/NF-kappaB
      physically interacts with VP1686. To understand the impact of this interaction on
      the NF-kappaB DNA binding activities in infected macrophages, we analyzed a
      series of deletion mutants for the TTSS and its secreted proteins. Induction of
      DNA binding activity of NF-kappaB was significantly suppressed, and increased
      macrophage apoptosis has been associated with V. parahaemolyticus strain, which
      contains both VP1686 and TTSS1. Macrophages lacking Toll-like receptor adaptor
      molecules MyD88 (myeloid differentiation primary response protein 88) or TRIF
      (TIR domain-containing adapter-inducing interferon beta) showed similar
      sensitivity to VP1686. As a consequence of NF-kappaB suppression, microarray
      analysis has revealed that VP1686 translocation alerted the expression of many
      genes that have known functions in cellular responses to apoptosis, cell growth,
      and transcriptional regulation. Our results suggest an important role for Vibrio
      effector protein VP1686 that activate a conserved apoptotic pathway in
      macrophages through suppression of NF-kappaB activation independent of Toll-like
      receptor signaling.

PMID- 16984917
TI  - A splice variant of CD99 increases motility and MMP-9 expression of human breast
      cancer cells through the AKT-, ERK-, and JNK-dependent AP-1 activation signaling
      pathways.
AB  - The CD99 gene encodes two distinct transmembrane proteins by alternative splicing
      of its transcript. To examine the effects of two CD99 isoforms on the invasive
      phenotypes of breast cancer cells, MDA-MB-231 and MCF-7 human breast cancer cell
      lines were stably transfected with CD99 cDNAs encoding the major wild-type form
      (type I) or a minor splice variant (type II). As a result, expression of CD99
      type II, but not type I, markedly elevated the motility, binding to fibronectin,
      MMP-9 expression, and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells.
      In MDA-MB-435 breast cancer cells expressing both CD99 type I and type II,
      invasion-related cellular activities were inhibited by the transfection of small
      interfering RNA (siRNA) targeted to CD99 type II. Meanwhile, CD99 type II-induced
      MMP-9 expression in MDA-MB-231 cells was shown to be mediated by the binding of
      AP-1 factors to the MMP-9 gene promoter. Gel shift assay revealed that ligation
      of CD99 type II with antibody resulted in the binding of JunD to the AP-1 site of
      the MMP-9 promoter region. Initiation of CD99 type II signaling by antibody
      ligation increased expression of JunD and FosB AP-1 factors, along with
      phosphorylation of Src, Akt, p38 MAPK, ERK, and JNK. Knockdown of JunD and FosB
      by siRNA transfection abolished the positive effects of CD99 type II on the
      motility and MMP-9 expression of MDA-MB-231 cells. Increased expression of JunD
      and FosB as well as elevated cell motility and MMP-9 expression by CD99 type II
      ligation were also abrogated by inhibitors, dominant-negative forms, and siRNAs
      for Akt1, ERK1/2, and JNK1 but not for p38 MAPK. These results suggest that
      expression of a splice variant of CD99 contributes to the invasive ability of
      human breast cancer cells by up-regulating AP-1-mediated gene expression through
      the Akt-dependent ERK and JNK signaling pathways.

PMID- 16984918
TI  - MARCO mediates silica uptake and toxicity in alveolar macrophages from C57BL/6
      mice.
AB  - Scavenger receptors (SR), on the surface of the macrophage, appear to be
      responsible for silica uptake and cell death signaling in the macrophage. The
      purpose of this study was to isolate which SRs (macrophage receptor with
      collagenous structure (MARCO), CD204, or CD36) were involved using a variety of
      SR single and double null mice. The findings indicated that MARCO was the
      critical SR involved in silica uptake and cytotoxicity in the primary alveolar
      macrophages (AM) from C57BL/6 mice, as there was no particle uptake or cell death
      in the absence of this SR. The level of MARCO expression on AM changed
      significantly with the absence of other SR, and silica uptake was proportional to
      cell surface MARCO expression. In addition, silica uptake and cytotoxicity were
      completely blocked by an anti-mouse MARCO antibody. Transfection of Chinese
      hamster ovary cells with human MARCO supported these conclusions, as silica
      particles bound to and initiated apoptosis in the MARCO-transfected cells. Strain
      differences with regard to SR distribution were also examined. There was a
      differential expression of these SR on AM from each strain, with MARCO dominant
      for C57BL/6, CD36 dominant on BALB/c, and all three SR expressed on 129/SvJ mice.
      Similar to the results with C57BL/6 AM, MARCO was involved with silica-induced
      cell death in the 129/SvJ strain. In contrast, BALB/c AM used an unidentified
      mechanism for silica uptake because the SR antibodies failed to block particle
      internalization. Taken together, these results indicate MARCO is the primary AM
      receptor interacting with silica, depending on mouse strain and level of
      constitutive expression.

PMID- 16984919
TI  - Regulation of Legionella phagosome maturation and infection through flagellin and
      host Ipaf.
AB  - Legionella pneumophila is an intracellular bacterium that causes an acute form of
      pneumonia called Legionnaires' disease. After infection of human macrophages, the
      Legionella-containing phagosome (LCP) avoids fusion with the lysosome allowing
      intracellular replication of the bacterium. In macrophages derived from most
      mouse strains, the LCP is delivered to the lysosome resulting in Legionella
      degradation and restricted bacterial growth. Mouse macrophages lacking the NLR
      protein Ipaf or its downstream effector caspase-1 are permissive to intracellular
      Legionella replication. However, the mechanism by which Ipaf restricts Legionella
      replication is not well understood. Here we demonstrate that the presence of
      flagellin and a competent type IV secretion system are critical for Legionella to
      activate caspase-1 in macrophages. Activation of caspase-1 in response to
      Legionella infection also required host Ipaf, but not TLR5. In the absence of
      Ipaf or caspase-1 activation, the LCP acquired endoplasmic reticulum-derived
      vesicles, avoided fusion with the lysosome, and allowed Legionella replication.
      Accordingly a Legionella mutant lacking flagellin did not activate caspase-1,
      avoided degradation, and replicated in wild-type macrophages. The regulation of
      phagosome maturation by Ipaf occurred within 2 h after infection and was
      independent of macrophage cell death. In vivo studies confirmed that flagellin
      and Ipaf play an important role in the control of Legionella clearance. These
      results reveal that Ipaf restricts Legionella replication through the regulation
      of phagosome maturation, providing a novel function for NLR proteins in host
      defense against an intracellular bacterium.

PMID- 16984920
TI  - Structural basis for substrate binding and regioselective oxidation of
      monosaccharides at C3 by pyranose 2-oxidase.
AB  - Pyranose 2-oxidase (P2Ox) participates in fungal lignin degradation by producing
      the H2O2 needed for lignin-degrading peroxidases. The enzyme oxidizes cellulose-
      and hemicellulose-derived aldopyranoses at C2 preferentially, but also on C3, to
      the corresponding ketoaldoses. To investigate the structural determinants of
      catalysis, covalent flavinylation, substrate binding, and regioselectivity, wild
      type and mutant P2Ox enzymes were produced and characterized biochemically and
      structurally. Removal of the histidyl-FAD linkage resulted in a catalytically
      competent enzyme containing tightly, but noncovalently bound FAD. This mutant
      (H167A) is characterized by a 5-fold lower kcat, and a 35-mV lower redox
      potential, although no significant structural changes were seen in its crystal
      structure. In previous structures of P2Ox, the substrate loop (residues 452-457)
      covering the active site has been either disordered or in a conformation
      incompatible with carbohydrate binding. We present here the crystal structure of
      H167A in complex with a slow substrate, 2-fluoro-2-deoxy-D-glucose. Based on the
      details of 2-fluoro-2-deoxy-D-glucose binding in position for oxidation at C3, we
      also outline a probable binding mode for D-glucose positioned for regioselective
      oxidation at C2. The tentative determinant for discriminating between the two
      binding modes is the position of the O6 hydroxyl group, which in the C2-oxidation
      mode can make favorable interactions with Asp452 in the substrate loop and,
      possibly, a nearby arginine residue (Arg472). We also substantiate our hypothesis
      with steady-state kinetics data for the alanine replacements of Asp452 and Arg472
      as well as the double alanine 452/472 mutant.

PMID- 16984921
TI  - Legionella pneumophila induces IFNbeta in lung epithelial cells via IPS-1 and
      IRF3, which also control bacterial replication.
AB  - Legionella pneumophila, a Gram-negative facultative intracellular bacterium,
      causes severe pneumonia (Legionnaires' disease). Type I interferons (IFNs) were
      so far associated with antiviral immunity, but recent studies also indicated a
      role of these cytokines in immune responses against (intracellular) bacteria.
      Here we show that wild-type L. pneumophila and flagellin-deficient Legionella,
      but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, or
      heat-inactivated Legionella induced IFNbeta expression in human lung epithelial
      cells. We found that factor (IRF)-3 and NF-kappaB-p65 translocated into the
      nucleus and bound to the IFNbeta gene enhancer after L. pneumophila infection of
      lung epithelial cells. RNA interference demonstrated that in addition to IRF3,
      the caspase recruitment domain (CARD)-containing adapter molecule IPS-1
      (interferon-beta promoter stimulator 1) is crucial for L. pneumophila-induced
      IFNbeta expression, whereas other CARD-possessing molecules, such as RIG-I
      (retinoic acid-inducible protein I), MDA5 (melanoma differentiation-associated
      gene 5), Nod27 (nucleotide-binding oligomerization domain protein 27), and ASC
      (apoptosis-associated speck-like protein containing a CARD) seemed not to be
      involved. Finally, bacterial multiplication assays in small interfering RNA
      treated cells indicated that IPS-1, IRF3, and IFNbeta were essential for the
      control of intracellular replication of L. pneumophila in lung epithelial cells.
      In conclusion, we demonstrated a critical role of IPS-1, IRF3, and IFNbeta in
      Legionella infection of lung epithelium.

PMID- 16984922
TI  - DNA unwinding by Escherichia coli DNA helicase I (TraI) provides evidence for a
      processive monomeric molecular motor.
AB  - The F plasmid TraI protein (DNA helicase I) plays an essential role in
      conjugative DNA transfer as both a transesterase and a helicase. Previous work
      has shown that the 192-kDa TraI protein is a highly processive helicase,
      catalytically separating >850 bp under steady-state conditions. In this report,
      we examine the kinetic mechanism describing DNA unwinding of TraI. The kinetic
      step size of TraI was measured under both single turnover and pre-steady-state
      conditions. The resulting kinetic step-size estimate was approximately 6-8 bp
      step(-1). TraI can separate double-stranded DNA at a rate of approximately 1100
      bp s(-1), similar to the measured unwinding rate of the RecBCD helicase, and
      appears to dissociate very slowly from the 3' terminus following translocation
      and strand-separation events. Analyses of pre-steady-state burst amplitudes
      indicate that TraI can function as a monomer, similar to the bacteriophage T4
      helicase, Dda. However, unlike Dda, TraI is a highly processive monomeric
      helicase, making it unique among the DNA helicases characterized thus far.

PMID- 16984923
TI  - CDCA4 is an E2F transcription factor family-induced nuclear factor that regulates
      E2F-dependent transcriptional activation and cell proliferation.
AB  - The TRIP-Br1/p34(SEI-1) family proteins participate in cell cycle progression by
      coactivating E2F1- or p53-dependent transcriptional activation. Here, we report
      the identification of human CDCA4 (also know as SEI-3/Hepp) as a novel target
      gene of transcription factor E2F and as a repressor of E2F-dependent
      transcriptional activation. Analysis of CDCA4 promoter constructs showed that an
      E2F-responsive sequence in the vicinity of the transcription initiation site is
      necessary for the E2F1-4-induced activation of CDCA4 gene transcription.
      Chromatin immunoprecipitation analysis demonstrated that E2F1 and E2F4 bound to
      an E2F-responsive sequence of the human CDCA4 gene. Like TRIP-Br1/p34(SEI-1) and
      TRIP-Br2 (SEI-2), the transactivation domain of CDCA4 was mapped within C
      terminal acidic region 175-241. The transactivation function of the CDCA4 protein
      was inhibited by E2F1-4 and DP2, but not by E2F5-8. Inhibition of CDCA4
      transactivation activity by E2F1 partially interfered with retinoblastoma protein
      overexpression. Conversely, CDCA4 suppressed E2F1-3-induced reporter activity.
      CDCA4 (but not acidic region-deleted CDCA4) suppressed E2F1-regulated gene
      promoter activity. These findings suggest that the CDCA4 protein functions as a
      suppressor at the E2F-responsive promoter. Small interfering RNA-mediated
      knockdown of CDCA4 expression in cancer cells resulted in up-regulation of cell
      growth rates and DNA synthesis. The CDCA4 protein was detected in several human
      cells and was induced as cells entered the G1/S phase of the cell cycle. Taken
      together, our results suggest that CDCA4 participates in the regulation of cell
      proliferation, mainly through the E2F/retinoblastoma protein pathway.

PMID- 16984924
TI  - Use of single and combined antithrombotic therapy and risk of serious upper
      gastrointestinal bleeding: population based case-control study.
AB  - OBJECTIVES: To assess the risk of serious upper gastrointestinal bleeding
      associated with the newer antithrombotic agents used alone or in combination with
      other antithrombotic drugs; to describe the trends in use of antithrombotic drugs
      in the background population. DESIGN: Population based case-control study.
      SETTING: Funen County, Denmark (population 470,000). SUBJECTS: 1443 cases of
      serious upper gastrointestinal bleeding identified during 2000-4; 57,720 age and
      sex matched controls. MAIN OUTCOME MEASURE: Exposure to low dose aspirin,
      clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic
      treatment. RESULTS: Adjusted odds ratios associating drug use with upper
      gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low
      dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for
      dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding
      figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3
      (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for
      dipyridamole and aspirin. Other combinations were used too infrequently to allow
      estimation. The number of treatment years needed to produce one excess case
      varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel
      alone. During the study period, exposure to combined antithrombotic regimens
      increased by 425% in the background population. CONCLUSION: Antithrombotic
      treatment is becoming increasingly aggressive. Combined antithrombotic treatment
      confers particular risk and is associated with high incidence of gastrointestinal
      bleeding.

PMID- 16984925
TI  - Diagnostic accuracy of preoperative magnetic resonance imaging in predicting
      curative resection of rectal cancer: prospective observational study.
AB  - OBJECTIVE: To assess the accuracy of preoperative staging of rectal cancer with
      magnetic resonance imaging to predict surgical circumferential resection margins.
      DESIGN: Prospective observational study of rectal cancers treated by colorectal
      multidisciplinary teams between January 2002 and October 2003. SETTING: 11
      colorectal units in four European countries. PARTICIPANTS: 408 consecutive
      patients presenting with all stages of rectal cancer and undergoing magnetic
      resonance imaging before total mesorectal excision surgery and histopathological
      assessment of the surgical specimen. MAIN OUTCOME MEASURES: Accuracy of magnetic
      resonance imaging in predicting a curative resection based on the histological
      yardstick of presence or absence of tumour at the margins of the specimen.
      RESULTS: 354 of the 408 patients had a clear circumferential resection margin
      (87%, 95% confidence interval 83% to 90%). Specificity for prediction of a clear
      margin by magnetic resonance imaging was 92% (327/354, 90% to 95%). High
      resolution scans were technically satisfactory in 93% (379/408). Surgical
      specimens were histopathologically graded as complete or moderate in 80%
      (328/408), and the median lymph node harvest was 12 (range 0-49). Magnetic
      resonance imaging predicted clear margins in 349 patients. At surgery 327 had
      clear margins (94%, 91% to 96%). CONCLUSION: High resolution magnetic resonance
      imaging accurately predicts whether the surgical resection margins will be clear
      or affected by tumour. This technique can be reproduced accurately in multiple
      centres to predict curative resection and warns the multidisciplinary team of
      potential failure of surgery, thus enabling selection of patients for
      preoperative treatment.

PMID- 16984926
TI  - Association between the metabolic syndrome and parental history of premature
      cardiovascular disease.

PMID- 16984928
TI  - Failed Amplatzer Septal Occluder device implantation due to an embryonic septal
      remnant.

PMID- 16984927
TI  - The relationship between coronary artery disease and abnormal glucose regulation
      in China: the China Heart Survey.
AB  - AIM: The aim of this article is to characterize the glucometabolic state of
      patients with coronary artery disease (CAD) in China. METHODS AND RESULTS: This
      multicentre study recruited 3513 patients hospitalized for CAD, of whom 35.1%
      were admissions for acute CAD and 64.9% were elective admissions for CAD. At
      entry, 1153 patients had known type 2 diabetes and 97 had newly diagnosed
      diabetes [fasting plasma glucose level (FPG) > or =7.0 mmol/L]. Oral glucose
      tolerance tests (OGTTs) performed in the remaining patients revealed that 26.9%
      had diabetes and 37.3% had impaired glucose regulation (IGR). The prevalence of
      abnormal glucose regulation (AGR) was similar in the acute and elective
      admissions groups. Overall, the proportion of patients with diagnosed diabetes
      increased from 32.8% at baseline to 52.9% post-OGTT analysis. In total, 87.4% of
      patients with IGR and 80.5% of patients with diabetes would have remained
      undiagnosed if OGTTs had not been performed. CONCLUSION: AGR is common in
      patients with CAD. The prevalence of AGR is underestimated by FPG testing alone.
      OGTTs should be routinely used to assess the glucometabolic state of patients
      with CAD. Individuals identified with IGR or type 2 diabetes should receive
      treatment to reduce the progression of AGR and associated complications.

PMID- 16984929
TI  - Predictors of stroke in high-risk patients after acute myocardial infarction:
      insights from the VALIANT Trial.
AB  - AIMS: We sought to determine risk models for predicting early and late stroke in
      a large cohort of high-risk post-myocardial infarction (MI) patients. METHODS AND
      RESULTS: We prospectively analysed data from 14 703 patients in the VALIANT trial
      with acute MI complicated by heart failure, left ventricular (LV) systolic
      dysfunction, or both. Patients were randomized 0.5-10 days after acute MI to
      valsartan, captopril, or their combination. We evaluated risk factors for early
      (<45 days) and late (>45 days) stroke by using multivariable Cox proportional
      hazards regression analyses with stepwise variable selection techniques applied
      to 92 pre-specified potential predictor variables. After randomization, 463
      (3.2%) patients had fatal (n = 124) or non-fatal (n = 339) strokes, with 134
      strokes occurring in the first 45 days. The strokes were classified as ischaemic
      (348), haemorrhagic (40), or of indeterminate cause (75). Estimated glomerular
      filtration rate and heart rate when in sinus rhythm were the most powerful
      predictors of early stroke (<45 days after MI), whereas diastolic blood pressure
      (DBP) >90 mmHg, prior stroke, and atrial fibrillation (AF) were the most powerful
      predictors of stroke overall. Ejection fraction and sex were not predictive of
      stroke in this cohort. CONCLUSION: Among high-risk patients presenting with MI
      but without initial neurological symptoms, the risk of stroke 6 weeks thereafter
      is 0.94% (95% CI 0.78-1.09). Of the most powerful baseline predictors of stroke,
      DBP and AF are amenable to therapeutic interventions and thus merit special
      attention in these patients.

PMID- 16984930
TI  - Lack of evidence on diets for obesity for children: a systematic review.
AB  - BACKGROUND: The prevalence of obesity has increased rapidly in most developed
      countries in the last decades, and this rise is now spreading to developing
      countries. Childhood obesity is also increasing. The UK government has set a
      target to halt the rise in childhood obesity by 2010. Dietary recommendations are
      a central component of any comprehensive weight-loss programme. A low-fat energy
      restricted diet is the conventional therapy for obesity, but alternative dietary
      interventions have been proposed in recent years. METHODS: We conducted a
      systematic review to assess dietary intervention studies designed to reduce
      weight in childhood and adolescence. The studies included overweight or obese
      children or adolescents in which there was a comparison group and change in body
      weight or BMI was reported. RESULTS: We identified only nine such studies, seven
      of which were randomized. Six were conducted in the USA, two in Cuba, and one in
      France. Low-carbohydrate and low-glycaemic-index diets appeared to be at least as
      effective as energy-restricted low-fat diets for short-term weight loss, but most
      studies were too small to be informative, and none provided evidence on long-term
      weight control. CONCLUSIONS: There is a marked mismatch between the public health
      importance of childhood obesity and the number and quality of the studies
      conducted so far to assess dietary interventions for weight reduction in
      childhood and adolescence, and little evidence to support the current
      recommendation of a low-fat energy-restricted diet. There is an urgent need for
      well-designed intervention studies of the long-term effectiveness of alternative
      diets to provide a basis for evidence-based recommendations.

PMID- 16984931
TI  - Genomics, epidemiology, and common complex diseases: let's not throw out the baby
      with the bathwater!

PMID- 16984933
TI  - Do sunlight and vitamin D reduce the likelihood of colon cancer? Time for a
      paradigm shift?

PMID- 16984934
TI  - Commentary: stairway to health.

PMID- 16984935
TI  - Differential parental weight and height contributions to offspring birthweight
      and weight gain in infancy.
AB  - BACKGROUND: Parental weight and height correlate with offspring birthweight and
      weight gain, suggesting genetic and environmental influences on fetal growth. The
      differential contributions of the mother's and father's height and weight to
      birthweight, or weight gain in infancy, remain unclear and were examined using
      data from the UK Millennium Cohort Study. METHODS: We calculated z-scores for
      birthweight and conditional weight gain to age 9 months (weight gain adjusted for
      birthweight) for 6811 term white singleton infants living with natural parents,
      using the British 1990 growth reference. We also calculated parental height and
      weight z-scores. The effects of parental size on birthweight and weight gain were
      analysed using multivariable regression, with a novel reparameterization to test
      for differences in effect size between mother and father. RESULTS: Maternal
      weight had a far greater influence than paternal weight on birthweight
      [coefficient for the difference between parents (95% CI): 0.15 (0.100.20)], while
      parental height contributions were similar [0.03 (-0.02 to 0.07)]. Weights and
      heights of mothers and fathers contributed equally to infant weight gain
      [difference coefficients -0.03 (-0.09 to 0.02) and 0.02 (-0.03 to 0.07),
      respectively]. CONCLUSIONS: The influences of parental height and weight on
      birthweight and infant weight gain are similar for the two parents, with the
      exception of the influence of weight on birthweight where the mother is much more
      influential than the father. Parental size associations with infant growth result
      from a complex combination of genetic and environmental influences. This novel
      reparameterization of parental anthropometry is applicable to other studies
      examining parental influences on offspring size and growth across the life
      course.

PMID- 16984936
TI  - Physical activity and the incidence of type 2 diabetes in the Shanghai women's
      health study.
AB  - BACKGROUND: Leisure-time physical activity (LPA) has been associated with a
      reduced risk of type 2 diabetes. However, the potential effect of other types of
      physical activity on type 2 diabetes is still uncertain. The aim of this study
      was to examine the effect of occupational, commuting, daily living, and LPA on
      the incidence of type 2 diabetes in a cohort of middle-aged women. METHODS: We
      prospectively followed 70,658 women who had no prior history of diabetes at study
      recruitment for 4.6 years. Participants completed in-person interviews at
      baseline that collected information on diabetes risk factors including physical
      activity habits. Anthropometric measurements were taken by trained interviewers.
      Multivariate-adjusted hazard ratios were estimated by levels of occupational,
      commuting, daily living, and LPA. RESULTS: We documented 1973 incident cases of
      diabetes during 326,625 person-years of follow-up. LPA and daily living physical
      activity (DPA) were associated with a moderately reduced risk of type 2 diabetes.
      The relative risk for type 2 diabetes associated with LPA and DPA categories were
      1.00, 0.89, 1.05, and 0.83, (P trend = 0.12) and 1.00, 0.98, 0.95, and 0.88, (P
      trend = 0.06) respectively. LPA was associated with lower risk of type 2 diabetes
      in employed participants (P trend = 0.09) while DPA was mainly associated with a
      reduction in risk in non-employed participants (P trend <0.01). While
      occupational physical activity was not associated with type 2 diabetes risk in
      this population, commuting to work was associated with a reduction in risk. A
      combination of DPA and LPA was associated with a reduced risk of type 2 diabetes.
      CONCLUSIONS: This study suggests that physical activity, either from leisure-time
      exercise or daily activity reduces the risk of type 2 diabetes in women,
      supporting the current health promotion efforts encouraging both exercise and non
      exercise activity levels.

PMID- 16984937
TI  - Sulphasalazine inhibits human antigen-specific immune responses in vivo.
AB  - OBJECTIVE: To study the effects of the antirheumatic drug sulphasalazine (SASP)
      on the immune system by analysing systemic and gut-associated immune responses.
      METHODS: A total of 23 healthy volunteers were treated with either SASP or
      placebo for 5 weeks in a double-blind fashion and immunised 2 weeks after the
      initiation of treatment. Specific immune responses were triggered by subcutaneous
      immunisation with tetanus toxoid and by peroral immunisation with inactivated
      influenza vaccine. The effects of treatment on specific immunity to tetanus and
      influenza were evaluated by enzyme-linked immunospot assay quantifying the number
      of circulating specific and total antibody-producing cells (spot-forming cells
      (SFC)) at 6, 8 and 10 days after immunisation. RESULTS: An immunosuppressive
      effect of SASP on systemic immune response was observed with a decrease in the
      total number of IgG-SFC, IgG anti-tetanus SFC and IgG anti-tetanus antibody
      levels in serum. SASP also exerted an immunosuppressive effect on the mucosa
      associated immune system as seen from its down-regulating effect on the total
      number of circulating IgA SFC. CONCLUSIONS: These data show firstly that SASP
      exerts an immunosuppressive effect on defined immune responses to immunisation in
      vivo, and secondly that both mucosa-associated and systemic immunity are affected
      by SASP treatment.

PMID- 16984938
TI  - Real-time quantitative PCR to detect changes in synovial gene expression in
      rheumatoid arthritis after corticosteroid treatment.
AB  - Synovial biomarkers are increasingly important in the development of novel
      therapeutic agents for the treatment of rheumatoid arthritis (RA). To identify
      biomarkers correlating with changes in clinical disease activity, real-time
      quantitative PCR (Q-PCR) was used to evaluate changes in synovial gene expression
      after treatment with corticosteroids. Patients with active RA received either
      oral prednisolone (n=10, 60 mg daily for the first week and 40 mg daily for the
      second week) or placebo (n=11) for 14 days. Real-time Q-PCR was used to quantify
      gene expression of tumour necrosis factor (TNF)alpha, IL1beta, IL8 and matrix
      metalloproteinase (MMP) 1 in synovial tissue samples obtained through an
      arthroscopic procedure before and after treatment. mRNA levels were reported as
      relative expression units compared with a cell-based standard. Statistical
      analysis was performed using an analysis of covariance model. Prednisolone
      markedly decreased IL8 and MMP1 expression compared with placebo, and the CIs
      excluded the likelihood of no effect. A trend towards reduction was seen in
      IL1beta and TNFalpha mRNA expression in the prednisolone group, although CIs
      included the value for no effect. These data suggest that Q-PCR can be used to
      measure synovial mRNA expression of mediators implicated in the pathogenesis of
      RA in small proof-of-concept trials.

PMID- 16984939
TI  - Formative research in clinical trial development: attitudes of patients with
      arthritis in enhancing prevention trials.
AB  - In preparation for randomised controlled trials (RCTs) of disease-modifying
      antirheumatic drugs in patients with early inflammatory arthritis (EIA),
      formative research was conducted to enhance the design of such trials. The
      objectives of this research were to (1) determine patients' educational needs as
      they relate to the necessary elements of informed consent; and (2) assess
      patients' interest in enrolling in a hypothetical prevention trial. In-depth
      interviews were conducted with nine patients. Seven patients were women and all
      but one white. The mean age was 48 years. During the 4-month enrolment period,
      only three patients with EIA were identified; six patients with longer duration
      of symptoms were also interviewed. Most patients were able to express the primary
      aim of a hypothetical prevention trial presented. Factors cited by patients
      favouring enrolment were potential for direct medical benefit and knowledge that
      they would be withdrawn from the trial if they developed symptoms. Factors cited
      by patients against enrolment were the inclusion of a placebo and general
      uncertainty regarding treatment required by the RCT design. Pending larger-scale
      empirical projects to explore patients' attitudes about prevention trials, small
      scale formative research in advance of such trials ought to be conducted.

PMID- 16984940
TI  - Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease
      samples: citrulline-dependent or not?
AB  - BACKGROUND: Antibodies directed against citrullinated proteins (eg anti-cyclic
      citrullinated peptide (CCP)) have excellent diagnostic and good prognostic
      potential for rheumatoid arthritis. Type 1 autoimmune hepatitis (AIH-1) is a
      chronic liver disease characterised by a variety of serum autoantibodies.
      Recently, in a large group of patients with AIH-1 without clear rheumatoid
      arthritis overlap, a relatively high percentage (9%) of anti-CCP2 positivity was
      scored. OBJECTIVES: To characterise the citrulline-dependence of the observed
      anti-CCP2 positivity in AIH-1 sera as well as in other groups of patients without
      rheumatoid arthritis (mainly rheumatic diseases). METHODS: Serum samples of 57
      patients with AIH-1 and 66 patients without rheumatoid arthritis, most of them
      reported as anti-CCP positive, were tested for citrulline-specific reactivity
      with a second generation anti-CCP kit, with the citrullinated and the
      corresponding non-citrullinated (arginine-containing) antigen. A subset of AIH-1
      sera was also tested with a CCP1 ELISA (and arginine control). RESULTS: The anti
      CCP2 reactivity of most non-rheumatoid arthritis rheumatic diseases samples (87
      93%) was citrulline-specific, whereas a relatively high percentage of AIH-1
      samples (42-50%) turned out to be reactive in a citrulline-independent manner.
      The use of citrullinated and non-citrullinated CCP1 peptides confirmed a high
      occurrence of citrulline-independent reactivity in AIH-1 samples. CONCLUSIONS: In
      rheumatoid arthritis and most non-rheumatoid arthritis rheumatologic disease
      sera, anti-CCP positivity is citrulline-dependent. However in some patients,
      particularly patients with AIH-1, citrulline-independent reactivity in the anti
      CCP2 test can occur. A positive CCP test in a non-rheumatic disease (eg liver
      disease) should therefore be interpreted with care, and preferably followed by a
      control ELISA with a non-citrullinated antigen.

PMID- 16984941
TI  - Risk and predictors of infection leading to hospitalisation in a large primary
      care-derived cohort of patients with inflammatory polyarthritis.
AB  - BACKGROUND: The increased mortality observed in patients with rheumatoid
      arthritis is partly due to an increased occurrence of serious infections. A
      retrospective study from the Mayo Clinic found that infection risk is increased
      in rheumatoid arthritis. In particular, serious infection was associated with
      severe disease and use of corticosteroids. Robust estimates are required from
      prospective studies of incident cases. OBJECTIVE: To examine the risk of
      infection leading to hospitalisation and potential factors associated with this
      risk in an unselected population of patients with inflammatory polyarthritis.
      DESIGN: A prospective cohort study comparing infection incidence in new-onset
      patients with inflammatory polyarthritis with local population experience.
      PATIENTS AND METHODS: 2108 patients with inflammatory polyarthritis from a
      community-based register were studied and followed up annually (median 9.2
      years). The rate of hospitalisations for serious infection was compared with the
      rate of hospitalisations in the regional population. The contribution of
      potential predictors was assessed by undertaking a within-cohort analysis.
      RESULTS: Overall, the incidence of infection was more than two and a half times
      that of the general population (varying by site). History of smoking,
      corticosteroid use and rheumatoid factor were found to be significantly
      independent predictors of infection-related hospitalisation. Patients with
      inflammatory polyarthritis with all three factors were more than seven times as
      likely to be hospitalised compared with the rest of the cohort. DISCUSSION: These
      findings provide background data on the risk of infection associated with
      rheumatoid arthritis, and are of particular interest given the current awareness
      of the risk of infection associated with anti-tumour necrosis factoralpha
      treatments.

PMID- 16984942
TI  - Abatacept improves both the physical and mental health of patients with
      rheumatoid arthritis who have inadequate response to methotrexate treatment.
AB  - OBJECTIVE: To examine the impact of added abatacept treatment on health related
      quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have
      inadequate response to methotrexate (MTX). METHODS: The impact of abatacept
      treatment on HRQoL was examined in a longitudinal, randomised double blind,
      placebo controlled clinical trial. Effects of treatment on HRQoL were examined
      using repeated measures analysis of covariance and comparing rates of change in
      HRQoL across treatment groups. The relationship between American College of
      Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL
      indicators was also examined. Finally, a responder analysis was used to examine
      the percentage of patients who improved by 0.5 SD in 12 months or who reached the
      normative levels seen in the US general population. RESULTS: Statistically
      significant improvements in the abatacept group relative to controls were
      observed across a range of HRQoL measures, including physical function, fatigue,
      all eight domains of the SF-36, and the physical and mental component summaries
      (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five
      out of eight SF-36 domains. By day 169, all HRQoL measures were significantly
      better with abatacept than with placebo. HRQoL gains were associated with greater
      ACR clinical improvement, and the effects were consistent for patients with
      different disease duration. A significantly greater percentage of patients
      treated with abatacept reached normative levels of PCS, MCS, physical
      functioning, and fatigue compared with patients treated with MTX alone.
      CONCLUSION: Combined abatacept and MTX treatment produces significant
      improvements across a wide range of HRQoL domains in patients with RA.

PMID- 16984943
TI  - Risk factors for lung cancer in patients with scleroderma: a nested case-control
      study.
AB  - OBJECTIVES: To study potential risk factors for the development of lung cancer in
      patients with scleroderma and explore the chronological relationship between
      onset of scleroderma symptoms and subtypes of lung cancer. METHOD: Linkage of two
      population-based registers to identify lung cancer cases and gender-matched
      controls with scleroderma, followed by retrospective case note review for
      clinical details. RESULTS: Patients with scleroderma who smoke are seven times
      more likely to develop lung cancer than non-smokers (p=0.008). Smokers with
      scleroderma and cancer smoke more than smokers with scleroderma without cancer
      (p=0.019). Pulmonary fibrosis and anti-topoisomerase antibody do not increase the
      risk of lung cancer. Peripheral lung tumours occur earlier after the onset of
      scleroderma symptoms than bronchogenic tumours (p=0.05). CONCLUSIONS: Smokers
      with scleroderma should be monitored for the presence of lung cancer and
      counselled to quit smoking. The earlier development of peripheral lung tumours is
      not consistent, with pulmonary fibrosis being an aetiological factor.

PMID- 16984944
TI  - Autoimmune thyroid disease is associated with a diagnosis of secondary Sjogren's
      syndrome in familial systemic lupus.
AB  - BACKGROUND: Autoimmune thyroid disease is common in systemic lupus erythematosus
      (SLE). About 20% of patients with SLE have secondary Sjogren's syndrome. METHODS:
      Families with more than one patient with SLE were identified. All patients met
      the revised classification criteria, although SLE-unaffected relatives were
      confirmed not to satisfy these criteria. Diagnosis of autoimmune thyroid disease
      and Sjogren's syndrome was made on the basis of a review of medical records,
      interview and questionnaire administered to patients with SLE, and by a
      questionnaire administered to SLE-unaffected subjects. RESULTS: Of a total of
      1138 patients with SLE, 169 had a diagnosis of Sjogren's syndrome. Of these 50
      (29.6%) patients also had autoimmune thyroid disease. Of the 939 patients with
      SLE with no diagnosis of Sjogren's syndrome, 119 (12.7%) had autoimmune thyroid
      disease (chi2 = 20.1, p = 0.000009). There was no association of a diagnosis of
      hypertension with secondary Sjogren's syndrome (42% vss 47%). Among 2291 SLE
      unaffected relatives, 44 had diagnosed primary Sjogren's syndrome and 16 (36.3%)
      of these also had autoimmune thyroid disease. 265 of 2247 (11.8%) subjects had
      autoimmune thyroid disease but no Sjogren's syndrome (chi2 = 24.2, p<0.001).
      CONCLUSIONS: Autoimmune thyroid disease is found in excess among patients with
      SLE with a diagnosis of secondary Sjogren's syndrome, as well as among their SLE
      unaffected relatives with a diagnosis of primary Sjogren's syndrome.

PMID- 16984945
TI  - Characteristics of pesticide pyrotechnic smoke devices.
AB  - Pesticide smoke generating products are widely used by amateurs and professionals
      but there is little published information available about their burn and
      deposition characteristics to enable the risks associated with using these
      devices to be assessed. This paper investigates their burn characteristics,
      deposition patterns, pesticide air concentrations and potential exposure to
      operators. Thirteen firings were carried out in different spaces with different
      ventilation conditions. Three types of devices were investigated: dicloran,
      permethrin and red dye. Pesticide air concentrations increased after firing,
      reaching a maximum determined by the room volume in approximately 10 min and
      decreasing exponentially as a result of ventilation and deposition. Ejected
      pesticide was present in the aerosol phase but there were only occasional traces
      of vapour. Settlement of pesticide was affected by surface orientation, height,
      sampling material and the pesticide-to-space volume ratio. The manufacturer's
      recommended treatment period for dicloran of 4 h followed by half an hour of
      ventilation may be insufficient to reduce pesticide to safe levels for re-entry
      under very calm conditions.

PMID- 16984947
TI  - A new sampler to assess dermal exposure during wet working.
AB  - In the UK, approximately 30% of cases of dermatitis reported to the national
      surveillance scheme are associated with wet working or exposure to aqueous
      mixtures. There is evidence that the duration and frequency that hands are wet
      are key determinants of risk, but there are no objective methods to measure these
      exposure factors. This research aimed to develop a practical tool to measure the
      duration and the number of occasions hands are wet. We developed an electronic
      sensor that is worn on the finger, which detects wetness from evaporative
      cooling. The output signal is recorded in electronic memory and the frequency and
      duration of exposure calculated using a simple data processing algorithm. The
      device has been tested in a variety of environmental conditions and for a
      standardized wet-work task. Wetting events were detectable in all the
      standardized tests, with the proportion of time the hands were wet ranging from
      15 to 49% (mean 30%). The electronic sensor is slightly affected by abrupt
      changes in air temperature and rapid air movements, but these do not seem to
      impose any practical limitations. This IOM Wet-Work sampler has the potential to
      provide reliable measurements of exposure that may be used to assess the risk of
      contact dermatitis.

PMID- 16984946
TI  - Urinary pesticide concentrations among children, mothers and fathers living in
      farm and non-farm households in iowa.
AB  - In the spring and summer of 2001, 47 fathers, 48 mothers and 117 children of Iowa
      farm and non-farm households were recruited to participate in a study
      investigating take-home pesticide exposure. On two occasions approximately 1
      month apart, urine samples from each participant and dust samples from various
      rooms were collected from each household and were analyzed for atrazine,
      metolachlor, glyphosate and chlorpyrifos or their metabolites. The adjusted
      geometric mean (GM) level of the urine metabolite of atrazine was significantly
      higher in fathers, mothers and children from farm households compared with those
      from non-farm households (P < or = 0.0001). Urine metabolites of chlorpyrifos
      were significantly higher in farm fathers (P = 0.02) and marginally higher in
      farm mothers (P = 0.05) when compared with non-farm fathers and mothers, but
      metolachlor and glyphosate levels were similar between the two groups. GM levels
      of the urinary metabolites for chlorpyrifos, metolachlor and glyphosate were not
      significantly different between farm children and non-farm children. Farm
      children had significantly higher urinary atrazine and chlorpyrifos levels (P =
      0.03 and P = 0.03 respectively) when these pesticides were applied by their
      fathers prior to sample collection than those of farm children where these
      pesticides were not recently applied. Urinary metabolite concentration was
      positively associated with pesticide dust concentration in the homes for all
      pesticides except atrazine in farm mothers; however, the associations were
      generally not significant. There were generally good correlations for urinary
      metabolite levels among members of the same family.

PMID- 16984948
TI  - Occupational exposure to mineral fibres: analysis of results stored on colchic
      database.
AB  - The aim of this paper is to present fibre exposure data recorded on the COLCHIC
      database. This database consolidates all occupational exposure data collected in
      French companies by the Caisses Regionales d'Assurance Maladie (regional health
      insurance funds, CRAM) and the Institut National de Recherche et de Securite
      (national institute for research and safety, INRS). A total of 8029 concentration
      results, expressed in number of fibres measured by phase-contrast optical
      microscopy, are available for exposure to asbestos fibres, ceramic fibres and man
      made mineral fibres other than ceramic fibres. Presentation of base data by
      activity branch, activity sector or workplace permits identification of
      situations, for which prevention efforts are most essential. Analysis of exposure
      levels during the 1986-2004 period show that these are broadly influenced by
      changes in the exposure limit values. Wearing of respiratory protection equipment
      by employees is also discussed. The data may be helpful to occupational
      physicians performing occupational screening of exposed workers and to
      epidemiologists seeking information for building job-exposures matrices. In this
      respect, a database (FIBREX) will be available on the INRS web site (www.inrs.fr)
      at the beginning of 2007. This database will provide a higher level of detail in
      activity and workplace description than that which was possible for practical
      reasons in this paper.

PMID- 16984949
TI  - Alleged allergenicity of latex gloves.

PMID- 16984950
TI  - Isolating recombinant antibodies against specific protein morphologies using
      atomic force microscopy and phage display technologies.
AB  - Isolation of antibodies to antigens that are either unstable, exist in multiple
      morphologies or have very limited availability can be prohibitively difficult.
      Here we describe a novel technique combining the capabilities of phage display
      antibody technology and atomic force microscopy (AFM) that is used to isolate
      antibody fragments that bind to a specific morphology of the target antigen,
      alpha-synuclein. AFM imaging allows us to both visualize the presence and
      morphology of the target antigen as well as to monitor the efficiency of each
      step in the bio-panning process. We demonstrate that phage displayed antibodies
      specific to the target antigen morphology can be isolated after only two rounds
      of selection. The target antigen, alpha-synuclein, has been correlated with the
      Parkinson's disease (PD). Accumulation of alpha-synuclein fibrillar aggregates
      into Lewy body inclusions is a hallmark feature of PD. While alpha-synuclein can
      form several different aggregate morphologies including oligomers, protofibrils
      and fibrils, the role of these morphologies in the progression of PD is not
      known. The successful selection of the recombinant antibody described here can
      have potential therapeutic value since the single-chain fragment variable (scFv)
      can be expressed intracellularly to control folding and toxicity of the specific
      protein aggregates.

PMID- 16984951
TI  - CYP6B1 and CYP6B3 of the black swallowtail (Papilio polyxenes): adaptive
      evolution through subfunctionalization.
AB  - Gene duplication provides essential material for functional divergence of
      proteins and hence allows organisms to adapt to changing environments. Following
      duplication events, redundant paralogs may undergo different evolutionary paths
      via processes known as nonfunctionalization, neofunctionalization, or
      subfunctionalization. Studies of adaptive evolution at the molecular level have
      progressed rapidly by computationally analyzing nucleotide substitution patterns
      but such studies are limited by the absence of information relating to
      alterations of function of the encoded enzymes. In this respect, evolution of the
      Papilio polyxenes cytochrome P450 monooxygenases (P450s) responsible for the
      adaptation of this insect to furanocoumarin-containing host plants provides an
      excellent model for elucidating the evolutionary fate of duplicated genes.
      Evidence from sequence and functional analysis in combination with molecular
      modeling indicates that the paralogous CYP6B1 and CYP6B3 genes in P. polyxenes
      have probably evolved via subfunctionalization after the duplication event by
      which they arose. Both enzymes have been under independent purifying selection as
      evidenced by the low dN/dS ratio in both the coding region and substrate
      recognition sites. Both enzymes have maintained their ability to metabolize
      linear and angular furanocoumarins albeit at different efficiencies. Comparisons
      of molecular models developed for the CYP6B3 and CYP6B1 proteins highlight
      differences in their binding modes that account for their different activities
      toward linear and angular furanocoumarins. That P. polyxenes maintains these 2
      furanocoumarin-metabolizing loci with somewhat different activities and
      expression patterns provides this species with the potential to acquire P450s
      with novel functions while maintaining those most critical to its exclusive
      feeding on its current range of host plants.

PMID- 16984952
TI  - Clinical evaluation of cuff and tube tip position in a newly designed paediatric
      preformed oral cuffed tracheal tube.
AB  - BACKGROUND: To assess the adequacy of the position of the tracheal tube cuff and
      tracheal tube tip in the recently introduced preformed oral Microcuff paediatric
      endotracheal tube (PET) using the manufacturers recommendations for Microcuff
      tracheal tube size selection. METHODS: With Hospital Ethics Committee approval
      and informed parental consent, the tracheas of children from birth to adolescence
      were orally intubated with the preformed oral Microcuff PET. First, the position
      of the tracheal tube's intubation depth mark in relation to the vocal cords was
      assessed. Second, the distance 'tracheal tube tip-to-carina' was endoscopically
      measured with the patient supine and the head in a neutral position and the tube
      placed with the centre mark at the lower incisors or alveolar ridge. RESULTS: A
      total of 166 children aged from 0.1 to 16.4 yr (median 5.9 yr) were studied. In
      five patients the intubation depth mark was above (5 mm each), in 22 patients at
      the level of and in the remaining 139 patients below the vocal cords. No
      endobronchial intubation occurred. In four patients the distance 'tracheal tube
      tip-to-carina' was smaller than the safety margin to prevent endobronchial
      intubation during head-neck flexion. CONCLUSION: The new oral preformed cuffed
      tracheal tubes allow safe placement in almost all patients when inserted
      according to the tube bend. The critically low tube tip and the high cuff
      positions in a few tubes when placed according to the tube bend requires clinical
      alertness.

PMID- 16984953
TI  - An evaluation of poor LMA CTrach views with a fibreoptic laryngoscope and the
      effectiveness of corrective measures.
AB  - BACKGROUND: The LMA CTrach++ system has integrated fibreoptics to enable viewing
      of the glottis to aid tracheal intubation via a laryngeal mask conduit. Earlier
      evaluations of this system had shown high success rates of insertion, ventilation
      and tracheal intubation, but frequent difficulty or failure to view the glottis.
      METHOD: We evaluated CTrach views in 100 patients. In 69 patients with partial or
      no views of the glottis, we evaluated the causes with the aid of an Olympus LF-DP
      fibreoptic laryngoscope passed through the CTrach. In those with poor views, we
      tested the effectiveness of simple corrective measures to improve the views and
      optimize CTrach placement. These included pushing the CTrach deeper in, partial
      withdrawal by 6 cm and reinsertion to correct epiglottic downfolding, withdrawal
      by 1 cm and applying forward lift to correct obstruction by the arytenoids, and
      complete removal to clean the fibreoptic ports followed by reinsertion when
      secretions were the problem. RESULTS: Downfolding of the epiglottis caused poor
      views in 57 patients, which was correctable in 51. Obstruction of the view by the
      arytenoids occurred in seven patients and by secretions in five, all of which
      were correctable. With the Ctrach, we were able to ventilate the lungs in all
      patients, view the glottis in 94 and intubate the trachea in 97 patients.
      CONCLUSION: Despite the ability to ventilate the lungs in all patients with the
      CTrach, poor initial views were very frequent, indicating suboptimal placement,
      although most poor views can be improved, leading to a high intubation success
      rate.

PMID- 16984954
TI  - Haemodynamic changes after intracisternal papaverine instillation during
      intracranial aneurysmal surgery.
AB  - Cerebral vasospasm remains a significant cause of mortality and morbidity after
      aneurysmal subarachnoid haemorrhage. Use of either intra-arterial or
      intracisternal papaverine as an alternative treatment of refractory cerebral
      vasospasm has been associated with various complications including haemodynamic
      instabilities. However, our search in literature did not reveal association of
      bradycardia and hypotension with the use of papaverine by either of these routes.
      Here, we describe a case of anterior communicating artery aneurysm with
      hydrocephalus. The patient underwent craniotomy and clipping of the aneurysm
      followed by third ventriculostomy. Instillation of papaverine at the surgical
      site caused significant haemodynamic changes possibly because of stimulation of
      hypothalamus in the third ventricle or vagal nuclei in the fourth ventricle, or
      even both. We recommend cautious use of intracisternal papaverine in such
      scenario especially when third ventriculostomy has been performed as an adjunct
      surgical procedure.

PMID- 16984955
TI  - Nonylphenol and octylphenol-induced apoptosis in human embryonic stem cells is
      related to Fas-Fas ligand pathway.
AB  - Human embryonic stem (hES) cells have been proposed as a source of various cell
      types for cell replacement therapy. Besides their potential in therapeutic uses,
      ES cells also have other potential applications, such as in drug discovery and in
      vitro screening assays of various toxicants. Nonylphenol (NP) and octylphenol
      (OP) are common environmental contaminants, known to disrupt the reproductive and
      endocrine system. However, little is known about their toxicological effects on
      early embryonic development in humans. In this study, we used undifferentiated
      hES cells and the neural progenitor cells derived from them to investigate the
      potential toxicity of NP and OP. Our results show that the cytotoxic effects of
      NP and OP involve DNA fragmentation, the major characteristic of apoptosis. The
      NP- and OP-induced apoptosis was concomitant with the increased activity of
      Caspase-8 and -3. Moreover, both Fas and Fas ligand (FasL) protein expressions
      were markedly increased in the NP- or OP-exposed hES cells. These results suggest
      that NP and OP are able to trigger apoptosis in hES cells via a pathway dependent
      on caspase activation and Fas-FasL interaction. In particular, hES cell-derived
      neural progenitor cells had a higher sensitivity to the toxicants than
      undifferentiated hES cells, thereby suggesting that the toxic stress response may
      differ depending on the developmental stage. These findings offer new
      perspectives for understanding the fundamental mechanisms in chemical-induced
      apoptosis in hES cells.

PMID- 16984956
TI  - Use of a pharmacokinetic-driven computational fluid dynamics model to predict
      nasal extraction of hydrogen sulfide in rats and humans.
AB  - Hydrogen sulfide (H2S) is a naturally occurring and industrially generated gas.
      Human exposure to H2S results in dose-related neurological, respiratory, and
      cardiovascular effects. Subchronic exposure of rats to 30 or 80 ppm H2S results
      in olfactory neuron loss and basal cell hyperplasia. Olfactory lesions commonly
      border main airflow streams in the rat, indicating an influence of airflow on H2S
      induced lesion locations. In this study, anatomically accurate computational
      fluid dynamics (CFD) models were used to quantitatively predict H2S tissue dose
      in rat and human nasal passages. Air-tissue flux was defined in terms of H2S
      solubility, diffusivity, and reaction kinetics in nasal tissue. Kinetic
      parameters for the rat were estimated from an air-tissue pharmacokinetic (PK)
      model that was fit to experimental nasal extraction (NE) data. Using this PK
      driven CFD model, predicted flux at the mid-dorsomedial meatus and the middle
      portion of the ethmoid recess showed a good correlation with olfactory lesion
      incidence. Scaled kinetic parameters were incorporated into a human CFD model to
      predict H2S flux in human nasal passages. Assuming that equivalent H2S flux
      values will induce similar responses in the olfactory regions of rats and humans,
      a no-observed-adverse-effect-level human-equivalent concentration was estimated
      to be 5 ppm. This estimate was based on quantitative tissue dose estimates
      extrapolated from both lesion and NE data in rats and represents a risk estimate
      that is science based and does not rely on simplified dosimetric assumptions for
      interspecies extrapolation.

PMID- 16984957
TI  - Hepatic gene downregulation following acute and subchronic exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - Chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to
      lead to the development of hepatotoxicity and carcinogenicity in the liver of
      female rats. In this study, we investigated hepatic gene downregulation in
      response to acute and subchronic TCDD exposure. We identified 61 probes which
      exhibited a downregulation of twofold or greater following subchronic (13 weeks)
      exposure to TCDD. Comparative analysis of the hepatic expression of these 61
      probes was conducted with rats subchronically exposed to PeCDF, PCB126, PCB153,
      and a mixture of PCB126 and PCB153. PCB153 produced little or no alteration in
      these probes, while the binary mixture mimicked most closely the downregulation
      observed with TCDD. To discern if the repression of genes within this probe set
      occur as a primary response to TCDD exposure, we analyzed the early
      responsiveness of 11 genes at 6, 24, and 72 h following a single exposure to
      TCDD. We observed early repression of the 11 genes within this early time course,
      indicating that the repression of this subset of genes occurs as a primary
      response to TCDD exposure and not as a secondary response to 13 weeks of
      subchronic treatment. In addition, the gender, species, and AhR dependence of
      these responses were also investigated. Gender- and species-dependent repression
      was observed within this subset of genes. Furthermore, utilizing AhR knockout
      mice, we were able to determine the AhR-dependent downregulation of seven of 11
      genes. Together these results assist efforts to understand the multitude of
      effects imposed by TCDD and AhR ligands on gene expression.

PMID- 16984958
TI  - A 28-day oral dose toxicity study enhanced to detect endocrine effects of
      hexabromocyclododecane in Wistar rats.
AB  - A 28-day repeated dose study in rats (OECD407) enhanced for endocrine and immune
      parameters was performed with hexabromocyclododecane (HBCD). Rats were exposed by
      daily gavage to HBCD dissolved in corn oil in 8 dose groups with doses ranging
      between 0 and 200 mg/kg bw per day (mkd). Evaluation consisted of dose-response
      analysis with calculation of a benchmark dose at the lower 95% one-sided
      confidence bound (BMDL) at predefined critical effect sizes (CESs) of 10-20%. The
      most remarkable findings were dose-related effects on the thyroid hormone axis,
      that is, decreased total thyroxin (TT4, BMDL 55.5 mkd at CES--10%), increased
      pituitary weight (29 mkd at 10%) and increased immunostaining of TSH in the
      pituitary, increased thyroid weight (1.6 mkd at 10%), and thyroid follicle cell
      activation. These effects were restricted to females. Female rats also showed
      increased absolute liver weights (22.9 mkd at 20%) and induction of T4-glucuronyl
      transferase (4.1 mkd at 10%), suggesting that aberrant metabolization of T4
      triggers feedback activation of the thyroid hormone system. These effects were
      accompanied by possibly secondary effects, including increased cholesterol (7.4
      mkd at 10%), increased tibial bone mineral density (> 49 mkd at 10%), both in
      females, and decreased splenocyte counts (0.3-6.3 mkd at 20%; only evaluated in
      males). Overall, female rats appeared to be more sensitive to HBCD than male
      rats, and an overall BMDL is proposed at 1.6 mkd, based on a 10% increase of the
      thyroid weight, which was the most sensitive parameter in the sequence of events.

PMID- 16984959
TI  - Glomerular targets of Heliothis subflexa male olfactory receptor neurons housed
      within long trichoid sensilla.
AB  - We used single-sensillum recordings to characterize male Heliothis subflexa
      antennal olfactory receptor neuron physiology in response to compounds related to
      their sex pheromone. The recordings were then followed by cobalt staining in
      order to trace the neurons' axons to their glomerular destinations in the
      antennal lobe. Receptor neurons responding to the major pheromone component, (Z)
      11-hexadecenal, in the first type of sensillum, type-A, projected axons to the
      cumulus of the macroglomerular complex (MGC). In approximately 40% of the type-A
      sensilla, a colocalized receptor neuron was stained that projected consistently
      to the posterior complex 1 (PCx1), a specific glomerulus in an 8-glomerulus
      complex that we call the Posterior Complex (PCx). We found that receptor neurons
      residing in type-B sensilla and responding to a secondary pheromone component,
      (Z)-9-hexadecenal, send their axons to the dorsal medial glomerulus of the MGC.
      As in the type-A sensilla, we found a cocompartmentalized neuron within type-B
      sensilla that sends its axon to a different glomerulus of the PCx4. One neuron in
      type-C sensilla tuned to a third pheromone component, (Z)-11-hexadecenol, and a
      colocalized neuron responding to (Z)-11-hexadecenyl acetate projected their axons
      to the anteromedial and ventromedial glomeruli of the MGC, respectively.

PMID- 16984960
TI  - Convergent linkage evidence from two Latin-American population isolates supports
      the presence of a susceptibility locus for bipolar disorder in 5q31-34.
AB  - We performed a whole genome microsatellite marker scan in six multiplex families
      with bipolar (BP) mood disorder ascertained in Antioquia, a historically isolated
      population from North West Colombia. These families were characterized clinically
      using the approach employed in independent ongoing studies of BP in the closely
      related population of the Central Valley of Costa Rica. The most consistent
      linkage results from parametric and non-parametric analyses of the Colombian scan
      involved markers on 5q31-33, a region implicated by the previous studies of BP in
      Costa Rica. Because of these concordant results, a follow-up study with
      additional markers was undertaken in an expanded set of Colombian and Costa Rican
      families; this provided a genome-wide significant evidence of linkage of BPI to a
      candidate region of approximately 10 cM in 5q31-33 (maximum non-parametric
      linkage score=4.395, P<0.00004). Interestingly, this region has been implicated
      in several previous genetic studies of schizophrenia and psychosis, including
      disease association with variants of the enthoprotin and gamma-aminobutyric acid
      receptor genes.

PMID- 16984961
TI  - Lentiviral vector expressing retinoic acid receptor beta2 promotes recovery of
      function after corticospinal tract injury in the adult rat spinal cord.
AB  - Spinal cord injury often results in permanent and devastating neurological
      deficits and disability. This is due to the limited regenerative capacity of
      neurones in the central nervous system (CNS). We recently demonstrated that a
      transcription factor retinoic acid receptor beta2 (RARbeta2) promoted axonal
      regeneration in adult sensory neurones located peripherally. However, it is not
      known if RARbeta2 can promote axonal regeneration in cortical neurones of the
      CNS. Here, we demonstrate that delivery of RARbeta2 via a lentiviral vector to
      adult dissociated cortical neurones significantly enhances neurite outgrowth on
      adult cortical cryosections, which normally provide an unfavourable substrate for
      growth. We also show that lentiviral-mediated transduction of corticospinal
      neurones resulted in robust transgene expression in layer V corticospinal
      neurones and their axonal projections in the corticospinal tract (CST) of the
      spinal cord. Expression of RARbeta2 in these neurones enhanced regeneration of
      the descending CST fibres after injury to these axons in the mid-cervical spinal
      cord. Furthermore, we observed functional recovery in sensory and locomotor
      behavioural tests in RARbeta2-treated animals. These results suggest that a
      direct and selective delivery of RARbeta2 to the corticospinal neurones promotes
      long-distance functional regeneration of axons in the spinal cord and may thus
      offer new therapeutic gene strategy for the treatment of human spinal cord
      injuries.

PMID- 16984962
TI  - Cystathionine beta-synthase is essential for female reproductive function.
AB  - In human reproduction, hyperhomocysteinemia has been reported as a risk factor
      for early pregnancy loss and congenital birth defects. Hyperhomocysteinemia is
      also recognized as a cause of maternal obstetric complications such as
      preeclampsia. The role of plasma hyperhomocysteinemia in female fertility was
      examined using cystathionine beta synthase knockout (cbs KO) mice. Cbs KO females
      were infertile, showed alterations in the estrus cycle and an increased
      progesterone response during pseudo-pregnancy induction. Both cbs KO ovaries and
      ovulated oocytes showed no major morphological alterations. However, placental
      and uterine masses were decreased at day 18 of pregnancy and showed morphological
      abnormalities. In cbs-KO pregnant females, the number of uterine implantation
      sites was not decreased despite the low number of surviving embryos. Fertility
      was restored when cbs-deficient ovaries were transplanted to normal ovarectomized
      recipients. We detected an increased uterine expression of Grp78, a marker of
      endoplasmic reticulum stress, which was accompanied by the decreased levels of
      uterine cbs mRNA in both hyperhomocysteinemic heterozygous (fertile) and
      homozygous (non-fertile) females. Our results indicate that cbs -/- female
      infertility is a consequence of the uterine failure and demonstrate that uterine
      endoplasmic reticulum stress and cbs expression are not determinant of
      infertility, suggesting that uterine dysfunction is a consequence of either
      hyperhomocysteinemia or other factor(s) in the uterine environment of cbs -/-
      animals. In summary, these studies demonstrate the potential importance of
      homocysteine levels for uterine handling of embryos.

PMID- 16984963
TI  - Behavioral abnormalities precede neuropathological markers in rats transgenic for
      Huntington's disease.
AB  - Huntington's disease (HD) is caused by an expanded CAG repeat leading to the
      synthesis of an aberrant protein and to the formation of polyglutamine (polyQ)
      containing inclusions and aggregates. Limited information is available concerning
      the association of neuropathological markers with the development of behavioral
      markers in HD. Using a previously generated transgenic rat model of HD (tgHD
      rat), we performed association studies on the time-course of behavioral symptoms
      (motor function, learning, anxiety) and the appearance of striatal atrophy, 1C2
      immunopositive aggregates and polyQ recruitment sites, a precursor to these
      aggregates. At the age of 1 month, tgHD rats exhibited reduced anxiety and
      improved motor performance, while at 6 months motor impairments and at 9 months
      cognitive decline occurred. In contrast, polyQ recruitment sites appeared at
      around 6-9 months of age, indicating that HD-like behavioral markers preceded the
      appearance of currently detectable neuropathological markers. Interestingly,
      numerous punctate sites containing polyQ aggregates were also seen in areas
      receiving afferents from the densely recruiting regions suggesting either
      transport of recruitment-competent aggregates to terminal projections where
      initially 1C2 positive aggregates were formed or different internal properties of
      neurons in different regions. Furthermore, striatal atrophy was observed at the
      age of 12 months. Taken together, our findings support the hypothesis of a
      dynamic process leading to region- and age-specific polyQ recruitment and
      aggregation. The dissociation of onset between behavioral and neuropathological
      markers is suggestive of as yet undetected processes, which contribute to the
      early phenotype of these HD transgenic rats.

PMID- 16984964
TI  - Functional genetic analysis of mutations implicated in a human speech and
      language disorder.
AB  - Mutations in the FOXP2 gene cause a severe communication disorder involving
      speech deficits (developmental verbal dyspraxia), accompanied by wide-ranging
      impairments in expressive and receptive language. The protein encoded by FOXP2
      belongs to a divergent subgroup of forkhead-box transcription factors, with a
      distinctive DNA-binding domain and motifs that mediate hetero- and
      homodimerization. Here we report the first direct functional genetic
      investigation of missense and nonsense mutations in FOXP2 using human cell-lines,
      including a well-established neuronal model system. We focused on three unusual
      FOXP2 coding variants, uniquely identified in cases of verbal dyspraxia,
      assessing expression, subcellular localization, DNA-binding and transactivation
      properties. Analysis of the R553H forkhead-box substitution, found in all
      affected members of a large three-generation family, indicated that it severely
      affects FOXP2 function, chiefly by disrupting nuclear localization and DNA
      binding properties. The R328X truncation mutation, segregating with
      speech/language disorder in a second family, yields an unstable, predominantly
      cytoplasmic product that lacks transactivation capacity. A third coding variant
      (Q17L) observed in a single affected child did not have any detectable functional
      effect in the present study. In addition, we used the same systems to explore the
      properties of different isoforms of FOXP2, resulting from alternative splicing in
      human brain. Notably, one such isoform, FOXP2.10+, contains dimerization domains,
      but no DNA-binding domain, and displayed increased cytoplasmic localization,
      coupled with aggresome formation. We hypothesize that expression of alternative
      isoforms of FOXP2 may provide mechanisms for post-translational regulation of
      transcription factor function.

PMID- 16984966
TI  - Mothers' stress and expectations as a function of time since child's cochlear
      implantation.
AB  - This study examined stress, attitudes, and expectations among mothers of deaf
      children who underwent cochlear implantation (CI), as related to time elapsed
      since surgery. Participants were 64 mothers of such children at different points
      in the implantation process: candidates, 0-3 years postimplantation, and more
      than 3 years later. Expectations in communication and academic domains decreased
      as time since implantation passed. No differences emerged in stress levels
      between the 3 groups. Higher levels of mothers' and fathers' education correlated
      with lower stress levels. Older mothers expressed lower levels on the cohesion
      dimension of family functioning. Findings suggested the need to consider mothers'
      expectations in the rehabilitation process and to encourage mothers' realistic
      expectations with regard to the effects of CI.

PMID- 16984965
TI  - Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and
      bipolar disorder.
AB  - The variability in phenotypic presentations and the lack of consistency of
      genetic associations in mental illnesses remain a major challenge in molecular
      psychiatry. Recently, it has become increasingly clear that altered promoter DNA
      methylation could play a critical role in mediating differential regulation of
      genes and in facilitating short-term adaptation in response to the environment.
      Here, we report the investigation of the differential activity of membrane-bound
      catechol-O-methyltransferase (MB-COMT) due to altered promoter methylation and
      the nature of the contribution of COMT Val158Met polymorphism as risk factors for
      schizophrenia and bipolar disorder by analyzing 115 post-mortem brain samples
      from the frontal lobe. These studies are the first to reveal that the MB-COMT
      promoter DNA is frequently hypomethylated in schizophrenia and bipolar disorder
      patients, compared with the controls (methylation rate: 26 and 29 versus 60%;
      P=0.004 and 0.008, respectively), particularly in the left frontal lobes
      (methylation rate: 29 and 30 versus 81%; P=0.003 and 0.002, respectively).
      Quantitative gene-expression analyses showed a corresponding increase in
      transcript levels of MB-COMT in schizophrenia and bipolar disorder patients
      compared with the controls (P=0.02) with an accompanying inverse correlation
      between MB-COMT and DRD1 expression. Furthermore, there was a tendency for the
      enrichment of the Val allele of the COMT Val158Met polymorphism with MB-COMT
      hypomethylation in the patients. These findings suggest that MB-COMT over
      expression due to promoter hypomethylation and/or hyperactive allele of COMT may
      increase dopamine degradation in the frontal lobe providing a molecular basis for
      the shared symptoms of schizophrenia and bipolar disorder.

PMID- 16984967
TI  - The spatial arrangement of ORC binding modules determines the functionality of
      replication origins in budding yeast.
AB  - In the quest to define autonomously replicating sequences (ARSs) in eukaryotic
      cells, an ARS consensus sequence (ACS) has emerged for budding yeast. This ACS is
      recognized by the replication initiator, the origin recognition complex (ORC).
      However, not every match to the ACS constitutes a replication origin. Here, we
      investigated the requirements for ORC binding to origins that carry multiple,
      redundant ACSs, such as ARS603. Previous studies raised the possibility that
      these ACSs function as individual ORC binding sites. Detailed mutational analysis
      of the two ACSs in ARS603 revealed that they function in concert and give rise to
      an initiation pattern compatible with a single bipartite ORC binding site.
      Consistent with this notion, deletion of one base pair between the ACS matches
      abolished ORC binding at ARS603. Importantly, loss of ORC binding in vitro
      correlated with the loss of ARS activity in vivo. Our results argue that
      replication origins in yeast are in general comprised of bipartite ORC binding
      sites that cannot function in random alignment but must conform to a
      configuration that permits ORC binding. These requirements help to explain why
      only a limited number of ACS matches in the yeast genome qualify as ORC binding
      sites.

PMID- 16984968
TI  - The bipartite architecture of the sRNA in an archaeal box C/D complex is a
      primary determinant of specificity.
AB  - The archaeal box C/D sRNP, the enzyme responsible for 2'-O-methylation of rRNA
      and tRNA, possesses a nearly perfect axis of symmetry and bipartite structure.
      This RNP contains two platforms for the assembly of protein factors, the C/D and
      C'/D' motifs, acting in conjunction with two guide sequences to direct
      methylation of a specific 2'-hydroxyl group in a target RNA. While this suggests
      that a functional asymmetric single-site complex complete with guide sequence and
      a single box C/D motif should be possible, previous work has demonstrated such
      constructs are not viable. To understand the basis for a bipartite RNP, we have
      designed and assayed the activity and specificity of a series of synthetic RNPs
      that represent a systematic reduction of the wild-type RNP to a fully single-site
      enzyme. This reduced RNP is active and exhibits all of the characteristics of
      wild-type box C/D RNPs except it is nonspecific with respect to the site of 2'-O
      methylation. Our results demonstrate that protein-protein crosstalk through Nop5p
      dimerization is not required, but that architecture plays a crucial role in
      directing methylation activity with both C/D and C'/D' motifs being required for
      specificity.

PMID- 16984969
TI  - CTD kinase I is required for the integrity of the rDNA tandem array.
AB  - The genomic stability of the rDNA tandem array is tightly controlled to allow
      sequence homogenization and to prevent deleterious rearrangements. In this
      report, we show that the absence of the yeast CTD kinase I (CTDK-I) complex in
      null mutant strains leads to a decrease in the number of tandem rDNA repeats.
      Reintroduction of the missing gene induces an increase of rDNA repeats to reach a
      copy number similar to that of the original strain. Interestingly, while
      expansion is dependent on Fob1, a protein required for replication fork blocking
      activity in rDNA, contraction occurs in the absence of Fob1. Furthermore,
      silencing of class II genes at the rDNA, a process connected to rDNA stability,
      is not affected. Ctk1, the kinase subunit of the CTDK-I complex is involved in
      various steps of mRNA synthesis. In addition, we have recently shown that Ctk1 is
      also implicated in rRNA synthesis. The results suggest that the RNA polymerase I
      transcription defect occurring in a ctk1 mutant strain causes rDNA contraction.

PMID- 16984970
TI  - The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP
      2 and ARH.
AB  - Clathrin-mediated endocytosis requires cargo-specific adaptor proteins that
      recognize specific receptors and recruit them into coated pits. ARH [also called
      low-density lipoprotein receptor (LDLR) adaptor protein] serves as an adaptor for
      LDLR endocytosis in liver. However, ARH is dispensable for LDL uptake by some
      other cell types. Here, we show that the adaptor Dab2 plays a major role in LDLR
      internalization in HeLa cells and fibroblasts. Dab2 mediates internalization of
      LDLRs but not transferrin receptors independently of ARH and the classic clathrin
      adaptor AP-2. If Dab2 is absent, ARH can mediate LDLR endocytosis, but its action
      requires AP-2. Furthermore, the rate of LDLR endocytosis is decreased when Dab2
      is absent and Dab2, but not ARH, catalyzes the efficient clustering of LDLR into
      coated pits. Dab2 activity requires its binding to clathrin, LDLR and
      phospholipids. Dab2 is also involved in moving LDLRs off filopodia. We suggest
      that Dab2 is a cargo-specific endocytic adaptor protein, stably associating with
      phospholipids and clathrin to sort LDLR to nascent-coated pits, whereas ARH might
      accelerate later steps in LDLR endocytosis in cooperation with AP-2.

PMID- 16984971
TI  - Adipophilin-enriched domains in the ER membrane are sites of lipid droplet
      biogenesis.
AB  - The prevailing hypothesis of lipid droplet biogenesis proposes that neutral
      lipids accumulate within the lipid bilayer of the ER membrane from where they are
      budded off, enclosed by a protein-bearing phospholipid monolayer originating from
      the cytoplasmic leaflet of the ER membrane. We have used a variety of methods to
      investigate the nature of the sites of ER-lipid-droplet association in order to
      gain new insights into the mechanism of lipid droplet formation and growth. The
      three-dimensional perspectives provided by freeze-fracture electron microscopy
      demonstrate unequivocally that at sites of close association, the lipid droplet
      is not situated within the ER membrane; rather, both ER membranes lie external to
      and follow the contour of the lipid droplet, enclosing it in a manner akin to an
      egg cup (the ER) holding an egg (the lipid droplet). Freeze-fracture
      cytochemistry demonstrates that the PAT family protein adipophilin is
      concentrated in prominent clusters in the cytoplasmic leaflet of the ER membrane
      closely apposed to the lipid droplet envelope. We identify these structures as
      sites at which lipids and adipophilin are transferred from ER membranes to lipid
      droplets. These findings call for a re-evaluation of the prevailing hypothesis of
      lipid droplet biogenesis.

PMID- 16984972
TI  - Dynamics and anchoring of heterochromatic loci during development.
AB  - Positioning a euchromatic gene near heterochromatin can influence its expression.
      To better understand expression-relevant changes in locus positioning, we
      monitored in vivo movement of centromeres and a euchromatic locus (with and
      without a nearby insertion of heterochromatin) in developing Drosophila tissue.
      In most undifferentiated nuclei, the rate of diffusion and step size of the locus
      is unaffected by the heterochromatic insertion. Interestingly, although the
      movement observed here is non directional, the heterochromatic insertion allows
      the flanking euchromatic region to enter and move within the heterochromatic
      compartment. This study also finds that a constraint on chromatin movement is
      imposed which is a factor of distance from the centric heterochromatic
      compartment. This restraint prevents the heterochromatic locus from moving away
      from the centric heterochromatin compartment. Therefore, because of the
      constraint, even distinct and non-random nuclear organizations can be attained
      from random chromatin movements. We also find a general constraint on chromatin
      movement is imposed during differentiation, which stabilizes changes in nuclear
      organization in differentiated nuclei.

PMID- 16984973
TI  - Real-time analysis of cAMP-mediated regulation of ciliary motility in single
      primary human airway epithelial cells.
AB  - Airway ciliary beat frequency regulation is complex but in part influenced by
      cyclic adenosine monophosphate (cAMP)-mediated changes in cAMP-dependent kinase
      activity, yet the cAMP concentration required for increases in ciliary beat
      frequency and the temporal relationship between ciliary beat frequency and cAMP
      changes are unknown. A lentiviral gene transfer system was developed to express a
      fluorescence resonance energy transfer (FRET)-based cAMP sensor in ciliated
      cells. Expression of fluorescently tagged cAMP-dependent kinase subunits from the
      ciliated-cell-specific foxj1 promoter enhanced expression in fully differentiated
      ciliated human airway epithelial cells, and permitted simultaneous measurements
      of ciliary beat frequency and cAMP (represented by the FRET ratio). Apical
      application of forskolin (1 microM, 10 microM, 20 microM) and, in permeabilized
      cells, basolateral cAMP (20 microM, 50 microM, 100 microM) caused dose-dependent,
      albeit similar and simultaneous-increases in cAMP and ciliary beat frequency.
      However, decreases in cAMP preceded decreases in ciliary beat frequency,
      suggesting that either cellular cAMP decreases before ciliary cAMP or the
      dephosphorylation of target proteins by phosphatases occur at a rate slower than
      the rate of cAMP hydrolysis.

PMID- 16984974
TI  - A novel domain on HLA-DRbeta chain regulates the chaperone role of the invariant
      chain.
AB  - The human lymphocyte antigen (HLA) class II region encodes highly polymorphic
      peptide receptors, which associate in the ER to the chaperone invariant chain
      (Ii). Ii facilitates assembly of class II subunits to functional peptide
      receptors. We searched for a conserved structure on HLA-DR polypeptides that
      mediates contact to a previously identified proline-rich class-II-binding
      sequence of Ii. Major histocompatibility complex (MHC) class II beta chain
      sequences exhibit two conserved tryptophan residues separated by 22 amino acids.
      Inspection of this motif in the X-ray structure of DR3 showed TrpTyr residues in
      the vicinity of the Ii-derived fragment CLIP. Five DRbeta mutants were produced.
      Mutation at Tyr123, Trp153 and Asp152 residues abolished interaction to the
      proline-rich sequence of Ii. All mutants formed heterodimers with DRalpha, were
      capable of binding an antigenic sequence and were expressed on the cell surface
      of transfected cells. In the presence of endogenous DRbeta chain however, the
      TyrAspTrp mutant was not cell-surface exposed and did not co-isolate with Ii or
      DRalpha. The competition of the mutant with the endogenous DRbeta for binding to
      DRalpha indicates that a structure on DRbeta chain regulates assembly of DR
      subunits. Hence, the chaperone function of Ii is mediated through a conserved
      region on the beta2 domain of class II.

PMID- 16984975
TI  - In vivo expression and functional characterization of the zinc transporter ZnT8
      in glucose-induced insulin secretion.
AB  - Insulin-secreting pancreatic beta cells are exceptionally rich in zinc. In these
      cells, zinc is required for zinc-insulin crystallization within secretory
      vesicles. Secreted zinc has also been proposed to be a paracrine and autocrine
      modulator of glucagon and insulin secretion in pancreatic alpha and beta cells,
      respectively. However, little is known about the molecular mechanisms underlying
      zinc accumulation in insulin-containing vesicles. We previously identified a
      pancreas-specific zinc transporter, ZnT-8, which colocalized with insulin in
      cultured beta cells. In this paper we studied its localization in human
      pancreatic islet cells, and its effect on cellular zinc content and insulin
      secretion. In human pancreatic islet cells, ZnT-8 was exclusively expressed in
      insulin-producing beta cells, and colocalized with insulin in these cells. ZnT-8
      overexpression stimulated zinc accumulation and increased total intracellular
      zinc in insulin-secreting INS-1E cells. Furthermore, ZnT-8-overexpressing cells
      display enhanced glucose-stimulated insulin secretion compared with control
      cells, only for a high glucose challenge, i.e. >10 mM glucose. Altogether, these
      data strongly suggest that the zinc transporter ZnT-8 is a key protein for both
      zinc accumulation and regulation of insulin secretion in pancreatic beta cells.

PMID- 16984976
TI  - Low peak bone mass and attenuated anabolic response to parathyroid hormone in
      mice with an osteoblast-specific deletion of connexin43.
AB  - Connexin43 (Cx43) is involved in bone development, but its role in adult bone
      homeostasis remains unknown. To overcome the postnatal lethality of Cx43 null
      mutation, we generated mice with selective osteoblast ablation of Cx43, obtained
      using a Cx43fl allele and a 2.3-kb fragment of the alpha1(I) collagen promoter to
      drive Cre in osteoblasts (ColCre). Conditionally osteoblast-deleted ColCre;Cx43
      /fl mice show no malformations at birth, but develop low peak bone mass and
      remain osteopenic with age, exhibiting reduced bone formation and defective
      osteoblast function. By both radiodensitometry and histology, bone mineral
      content increased rapidly and progressively in adult Cx43+/fl mice after
      subcutaneous injection of parathyroid hormone (PTH), an effect significantly
      attenuated in ColCre;Cx43-/fl mice, with Cx43-/fl exhibiting an intermediate
      response. Attenuation of PTH anabolic action was associated with failure to
      increase mineral apposition rate in response to PTH in ColCre;Cx43-/fl, despite
      an increased osteoblast number, suggesting a functional defect in Cx43-deficient
      bone-forming cells. In conclusion, lack of Cx43 in osteoblasts leads to
      suboptimal acquisition of peak bone mass, and hinders the bone anabolic effect of
      PTH. Cx43 represents a potential target for modulation of bone anabolism.

PMID- 16984977
TI  - Bayesian method for gene detection and mapping, using a case and control design
      and DNA pooling.
AB  - Association mapping studies aim to determine the genetic basis of a trait. A
      common experimental design uses a sample of unrelated individuals classified into
      2 groups, for example cases and controls. If the trait has a complex genetic
      basis, consisting of many quantitative trait loci (QTLs), each group needs to be
      large. Each group must be genotyped at marker loci covering the region of
      interest; for dense coverage of a large candidate region, or a whole-genome scan,
      the number of markers will be very large. The total amount of genotyping required
      for such a study is formidable. A laboratory effort efficient technique called
      DNA pooling could reduce the amount of genotyping required, but the data
      generated are less informative and require novel methods for efficient analysis.
      In this paper, a Bayesian statistical analysis of the classic model of McPeek and
      Strahs is proposed. In contrast to previous work on this model, I assume that
      data are collected using DNA pooling, so individual genotypes are not directly
      observed, and also account for experimental errors. A complete analysis can be
      performed using analytical integration, a propagation algorithm for a hidden
      Markov model, and quadrature. The method developed here is both statistically and
      computationally efficient. It allows simultaneous detection and mapping of a QTL,
      in a large-scale association mapping study, using data from pooled DNA. The
      method is shown to perform well on data sets simulated under a realistic
      coalescent-with-recombination model, and is shown to outperform classical single
      point methods. The method is illustrated on data consisting of 27 markers in an
      880-kb region around the CYP2D6 gene.

PMID- 16984978
TI  - Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in
      muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by
      locoregional surgical treatment.
AB  - BACKGROUND: Tumor proliferation and apoptosis may be influenced by the mdm-2 gene
      product, which can block the antiproliferative effects of p53. bcl-2, one of a
      family of related genes that regulates the apoptotic pathway, exhibits a negative
      influence. Both individual and cooperative effects of these gene products may
      affect the biological behavior of primary bladder cancers and long-term outcome
      to standard therapy. METHODS: This study retrospectively evaluated the
      association with survival of mdm-2, p53, and bcl-2 expression in 59 patients with
      muscle-invasive, node-negative transitional cell carcinoma (TCC) treated with neo
      adjuvant chemotherapy followed by locoregional surgery. Each marker was defined
      as an altered phenotype if >or=20% malignant cells in the primary tumor exhibited
      staining; normal or minimal expression was defined as <20% cells exhibiting
      staining. RESULTS: Altered mdm-2, p53, and bcl-2 expression was observed in 37%,
      54%, and 46% of patients, respectively. In single marker analysis, altered p53
      expression correlated with long-term survival (P = 0.05) but mdm-2 (P = 0.42) or
      bcl-2 (P = 0.17) did not. In the multiple-marker analysis, a prognostic index
      simultaneously assessing mdm-2, p53, and bcl-2 correlated with survival (P =
      0.01). The 5-year survival for patients in which all markers were normally
      expressed was 54% compared with 25% in those with all three markers aberrantly
      expressed. Patients with aberrant expression of either one or two markers had an
      intermediate 5-year survival (49%). There was no association of molecular markers
      either alone or in combination with pathologic downstaging after neo-adjuvant
      chemotherapy. CONCLUSION: The cooperative effects of phenotypes determined by mdm
      2, p53, and bcl-2 expression may predict survival in patients with muscle
      invasive TCC of the bladder.

PMID- 16984979
TI  - Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta
      analysis of the randomised trials.
AB  - BACKGROUND: Despite several investigations, second malignancy risks (SMR)
      following radiotherapy alone (RT), chemotherapy alone (CT) and combined
      chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial.
      PATIENTS AND METHODS: We sought individual patient data from randomised trials
      comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF)
      versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of
      salvage treatment) were compared using Peto's method. RESULTS: Data for between
      53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT
      (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial
      treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P
      = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally
      higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P
      = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant
      difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P
      = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as
      initial therapy for HL decreases overall SMR by reducing relapse and need for
      salvage therapy. Administration of RT additional to CT marginally increases
      overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was
      substantially higher after EF-RT. Caution is needed in applying these findings to
      current therapies.

PMID- 16984980
TI  - Neurodevelopmental outcomes of neonates with medically and surgically treated
      necrotizing enterocolitis.
AB  - OBJECTIVES: (1) To characterise neurodevelopmental outcome of neonates with
      necrotizing enterocolitis (NEC); (2) to define whether NEC increases risk of
      neurodevelopmental impairment in very low birth weight neonates; (3) to
      investigate whether stage of disease or need for surgery increase risk of poor
      outcome. DESIGN: A systematic review was performed. Searches identified 182
      relevant papers. Ten studies compared extremely low birthweight neonates with NEC
      to infants of similar age and gestation who did not develop NEC. Data are
      reported as OR (95% CIs, p values for test for overall effect) and compared by
      chi2. RESULTS: 7843 children (821 with NEC) were included in the meta-analysis.
      Median follow-up was 20 months (range 12 to 156). Overall, 45% of children who
      had neonatal NEC were neurodevelopmentally impaired. Infants with NEC were
      significantly more likely than infants of similar age and gestation who did not
      develop NEC to be neurodevelopmentally impaired (1.6 (1.3 to 2.0), p = 0.0001)
      including a higher risk of cerebral palsy (1.5 (1.2 to 2.0), p = 0.001), visual
      (2.3 (1.0 to 5.1), p = 0.04), cognitive (1.7 (1.4 to 2.2), p<0.0001) and
      psychomotor impairment (1.7 (1.3 to 2.2), p<0.0001). The odds ratio of
      neurodevelopmental impairment was also 2.3 times higher in neonates with Bell's
      stage III disease or requiring surgery ((1.5 to 3.6), p = 0.0001). CONCLUSIONS:
      NEC is associated with significantly worse neurodevelopmental outcome than
      prematurity alone. Presence of advanced NEC and need for surgery increase the
      risk of neurological impairment.

PMID- 16984981
TI  - Serum adiponectin and coronary heart disease risk in older Black and White
      Americans.
AB  - CONTEXT: Adiponectin may influence the risk of coronary heart disease (CHD)
      independently of traditional cardiovascular risk factors. OBJECTIVE: Because body
      composition and adiponectin levels vary by race, we examined the relationship of
      adiponectin with prevalent and incident CHD in a cohort of older Black and White
      adults. DESIGN AND SETTING: We conducted a cross-sectional and prospective cohort
      study at two U.S. clinical centers. PARTICIPANTS: Participants included 3075 well
      functioning adults between ages 70 and 79 yr enrolled in the Health, Aging, and
      Body Composition study. MAIN OUTCOME MEASURES: Prevalent CHD was defined as
      history of myocardial infarction, coronary artery bypass graft, percutaneous
      coronary transluminal angioplasty, angina, or major electrocardiogram
      abnormalities. After excluding those with prevalent CHD, incident CHD was defined
      as hospitalized myocardial infarction or CHD death. RESULTS: At baseline, 602
      participants (19.6%) had CHD. During 6 yr of follow-up, 262 (10.6%) incident CHD
      events occurred. Whites had higher median adiponectin than Blacks (12 vs. 8
      microg/ml, P < 0.001). Race modified the effect of adiponectin (P for interaction
      was 0.002 for prevalent CHD, and P = 0.02 for incident CHD). Among Whites, an
      inverse association of adiponectin with CHD was explained by high-density
      lipoprotein and glucose. Among Blacks, a doubling of adiponectin was associated
      with a 40% higher risk of both prevalent CHD (odds ratio, 1.41; 95% confidence
      interval, 1.11-1.78) and incident CHD (hazards ratio, 1.37; 95% confidence
      interval, 1.01-1.87) after adjusting for explanatory variables. CONCLUSION: High
      circulating concentrations of adiponectin were associated with higher risk of CHD
      in older Blacks, even accounting for traditional CHD risk factors.

PMID- 16984982
TI  - Atrophy and impaired muscle protein synthesis during prolonged inactivity and
      stress.
AB  - CONTEXT: We recently demonstrated that 28-d bed rest in healthy volunteers
      results in a moderate loss of lean leg mass and strength. OBJECTIVE: The
      objective of this study was to quantify changes in muscle protein kinetics, body
      composition, and strength during a clinical bed rest model reflecting both
      physical inactivity and the hormonal stress response to injury or illness.
      DESIGN: Muscle protein kinetics were calculated during a primed, continuous
      infusion (0.08 micromol/kg.min) of 13C6-phenylalanine on d 1 and 28 of bed rest.
      SETTING: The setting for this study was the General Clinical Research Center at
      the University of Texas Medical Branch. PARTICIPANTS: Participants were healthy
      male volunteers (n = 6, 28 +/- 2 yr, 84 +/- 4 kg, 178 +/- 3 cm). INTERVENTION:
      During bed rest, hydrocortisone sodium succinate was administered iv (d 1 and 28)
      and orally (d 2-27) to reproduce plasma cortisol concentrations consistent with
      trauma or illness (approximately 22 microg/dl). MAIN OUTCOME MEASURES: We
      hypothesized that inactivity and hypercortisolemia would reduce lean muscle mass,
      leg extension strength, and muscle protein synthesis. RESULTS: Volunteers
      experienced a 28.4 +/- 4.4% loss of leg extension strength (P = 0.012) and a 3
      fold greater loss of lean leg mass (1.4 +/- 0.1 kg) (P = 0.004) compared with our
      previous bed rest-only model. Net protein catabolism was primarily due to a
      reduction in muscle protein synthesis [fractional synthesis rate, 0.081 +/- 0.004
      (d 1) vs. 0.054 +/- 0.007%/h (d 28); P = 0.023]. There was no change in muscle
      protein breakdown. CONCLUSION: Prolonged inactivity and hypercortisolemia
      represents a persistent catabolic stimulus that exacerbates strength and lean
      muscle loss via a chronic reduction in muscle protein synthesis.

PMID- 16984983
TI  - An acute increase in skeletal muscle carnitine content alters fuel metabolism in
      resting human skeletal muscle.
AB  - CONTEXT: Carnitine plays an essential role in the integration of fat and
      carbohydrate oxidation in skeletal muscle, which is impaired in obesity and type
      2 diabetes. OBJECTIVE: The aim of the present study was to investigate the effect
      of an increase in skeletal muscle total carnitine (TC) content on muscle fuel
      metabolism. DESIGN: A 5-h iv infusion of saline (control) or l-carnitine was
      administered while serum insulin was maintained at a physiologically high
      concentration during two randomized visits. PARTICIPANTS: Seven healthy,
      nonvegetarian young men (body mass index, 26.1 +/- 1.6 kg/m2) participated in the
      present study at the University of Nottingham. MAIN OUTCOME MEASURES: Skeletal
      muscle pyruvate dehydrogenase complex (PDC) activity and associated muscle
      metabolites were measured. RESULTS: The combination of hypercarnitinemia (600
      micromol/liter) and hyperinsulinemia (160 mU/liter) increased muscle TC content
      by 15% (P < 0.01) and was associated with decreased pyruvate dehydrogenase
      complex activity (P < 0.05) and muscle lactate content (P < 0.05) by 30 and 40%,
      respectively, and an overnight increase in muscle glycogen (P < 0.01) and long
      chain acyl-coenzyme A content (P < 0.05) by 30 and 40%, respectively, compared
      with control. CONCLUSIONS: These results suggest that an acute increase in human
      skeletal muscle TC content results in an inhibition of carbohydrate oxidation in
      conditions of high carbohydrate availability, possibly due to a carnitine
      mediated increase in fat oxidation. These novel findings may have important
      implications for our understanding of the regulation of muscle fat oxidation,
      particularly during exercise, when carnitine availability may limit fat
      oxidation, and in obesity and type 2 diabetes where it is known to be impaired.

PMID- 16984984
TI  - Association between aldosterone production and variation in the 11beta
      hydroxylase (CYP11B1) gene.
AB  - CONTEXT: Variation in the region of chromosome 8 including the genes steroid
      11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) influences
      mineralocorticoid and glucocorticoid metabolism. However, the relative importance
      of polymorphisms in CYP11B1 and CYP11B2 in determining these phenotypes is
      unknown. OBJECTIVE: Our objective was to investigate genetic influences of the
      CYP11B1 and CYP11B2 genes on mineralocorticoid metabolism. DESIGN: We measured 24
      h urinary excretion of the key metabolites of the principal mineralocorticoids,
      glucocorticoids and androgens secreted by the adrenal cortex. We genotyped
      polymorphisms spanning the CYP11B1 and CYP11B2 genes, which together capture all
      common variations at the locus. PARTICIPANTS: Participants included 573 members
      of 105 British Caucasian families ascertained on a hypertensive proband. MAIN
      OUTCOME MEASURES: We assessed heritability of urinary tetrahydroaldosterone
      (THAldo) excretion and association of THAldo excretion with genotype. RESULTS:
      The heritability of THAldo excretion was 52% (P < 10(-6)). There was significant
      association between THAldo and genotype at several of the CYP11B1/B2
      polymorphisms. The strongest association was observed at the rs6387 (2803A/G)
      polymorphism in intron 3 of CYP11B1 (P = 0.0004). Association followed a
      codominant model with a 21% higher THAldo excretion per G allele. Genotype at
      rs6387 accounted for 2.1% of the total population variability of THAldo. We found
      significant association between THAldo excretion and urinary total androgen
      excretion, urinary tetrahydrodeoxycortisol level, and urinary cortisol
      metabolites (all P < 0.001). CONCLUSIONS: Aldosterone synthesis is highly
      heritable and is affected by genotype at CYP11B1. Our findings support the
      hypothesis that genetically determined differences in 11-hydroxylation efficiency
      can have downstream effects on mineralocorticoid synthesis. Such effects may be
      of relevance to the development of low-renin essential hypertension.

PMID- 16984985
TI  - Association between neuromedin U gene variants and overweight and obesity.
AB  - BACKGROUND: Neuromedin U (NMU) is an anorexic neuropeptide expressed in the
      hypothalamus. Mice lacking the NmU gene are hyperphagic and obese, whereas mice
      overexpressing Nmu are hypophagic and lean. OBJECTIVE: Our objective was to
      investigate whether variants in NMU are associated with human obesity. DESIGN:
      The coding region of NMU was analyzed for variants in obese Czech children and
      obese Danish adults. Identified missense variants were investigated for
      cosegregation with obesity in families or association with obesity in the general
      population. SETTING: The study was performed at Steno Diabetes Center, Denmark,
      and Department of Pediatrics, Charles University, Czech Republic. SUBJECTS AND
      METHODS: A total of 289 Czech children and adolescents with early-onset obesity
      and 84 Danish obese adults were analyzed for variants in NMU. A NMU Ala19Glu
      polymorphism was genotyped in 5851 Danish subjects of the Inter99 cohort, and a
      rare NMU Arg165Trp mutation was sequenced in the proband family and in 53 lean
      and unrelated Czech subjects. RESULTS: The rare NMU Arg165Trp variant
      cosegregated with childhood obesity in a Czech family. Homozygous carriers of the
      Glu allele of the NMU Ala19Glu polymorphism were more common in the overweight
      and obese subjects; the Glu/Glu frequency was 0.4 (95% confidence interval, 0.2
      0.6) among 2586 lean subjects (BMI < 25 kg/m2) and 0.9 (95% confidence interval,
      0.7-1.1) among 3265 overweight and obese subjects (body mass index >or= 25 kg/m2)
      [odds ratio, 2.5 (1.2-5.3); P = 0.01]. CONCLUSION: Amino acid variants in NMU
      associate with overweight and obesity, suggesting that NMU is involved in energy
      regulation in humans.

PMID- 16984986
TI  - Impact of type 2 diabetes on myocardial insulin sensitivity to glucose uptake and
      perfusion in patients with coronary artery disease.
AB  - BACKGROUND AND HYPOTHESIS: Myocardial insulin resistance (IR) is a feature of
      coronary artery disease (CAD) with reduced left ventricular ejection fraction
      (LVEF). Whether type 2 diabetes mellitus (T2DM) with CAD and preserved LVEF
      induces myocardial IR and whether insulin in these patients acts as a myocardial
      vasodilator is debated. METHODS: We studied 27 CAD patients (LVEF > 50%): 12 with
      T2DM (CAD+DM), 15 without T2DM (CAD-NoDM). Regional myocardial and skeletal
      glucose uptake, myocardial and skeletal muscle perfusion were measured with
      positron emission tomography. Myocardial muscle perfusion was measured at rest
      and during hyperemia in nonstenotic and stenotic regions with and without acute
      hyperinsulinemia. RESULTS: Myocardial glucose uptake was similar in CAD+DM and
      CAD-NoDM in both nonstenotic and stenotic regions [0.38 +/- 0.08 and 0.36 +/-
      0.11 micromol/g.min; P value nonsignificant (NS)] and (0.35 +/- 0.09 and 0.37 +/-
      0.13 micromol/g.min; P = NS). Skeletal glucose uptake was reduced in CAD+DM (0.05
      +/- 0.04 vs. 0.10 +/- 0.05 micromol/g.min; P = 0.02), and likewise, whole-body
      glucose uptake was reduced in CAD+DM (4.0 +/- 2.8 vs. 7.0 +/- 2.4 mg/kg.min; P =
      0.01). Insulin did not alter myocardial muscle perfusion at rest or during
      hyperemia. Insulin increased skeletal muscle perfusion in CAD-NoDM (0.11 +/- 0.03
      vs. 0.06 +/- 0.03 ml/g.min; P = 0.02), but not in CAD+DM (0.08 +/- 0.04 and 0.09
      +/- 0.05 ml/g.min; P = NS). CONCLUSION: Myocardial IR to glucose uptake is not an
      inherent feature in T2DM patients with preserved LVEF. Acute physiological
      insulin exposure exerts no coronary vasodilation in CAD patients irrespective of
      T2DM.

PMID- 16984987
TI  - Progesterone regulation of human granulosa/luteal cell viability by an RU486
      independent mechanism.
AB  - CONTEXT: Progesterone (P4) inhibits human granulosa/luteal cell apoptosis by an
      unknown mechanism. OBJECTIVE: Our objective was to assess the role of the nuclear
      P4 receptor (PGR) and PGR membrane component 1 (PGRMC1) in mediating P4's
      antiapoptotic action in human granulosa/luteal cells. DESIGN, SETTING, AND
      PATIENTS: In vitro laboratory studies were designed in which human
      granulosa/luteal cells were harvested from in vitro fertilization patients from
      2004-2006. MAIN OUTCOME MEASURE: Apoptosis was assessed by terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays and
      DNA staining. Protein expression was observed by Western blot and
      immunocytochemistry. RESULTS: PGR was detected in 20% of the human
      granulosa/luteal cells, and 25 and 50 microM RU486 induced at least 70% of the
      cells to undergo apoptosis. Five micromolar RU486 neither induced apoptosis nor
      attenuated the antiapoptotic action of 1 microM P4. PGRMC1 and its binding
      partner, plasminogen activator inhibitor RNA-binding protein-1 (PAIRBP1), were
      detected in human granulosa/luteal cells. Antibodies to either PGRMC1 or PAIRBP1
      completely attenuated P4's action. CONCLUSIONS: PGR does not exclusively mediate
      P4's action because 1) 5 microM RU486 should have been able to override the
      antiapoptotic action of 1 microM P4 because RU486 binds to the PGR at a greater
      affinity than P4; 2) 25 and 50 microM RU486 induce three to four times more cells
      to undergo apoptosis than express PGR; 3) P4 must be continuously present to
      prevent apoptosis, which implies a rapid, possibly membrane-initiated mechanism
      of action; and 4) expression and blocking antibody studies suggest that PGRMC1
      and PAIRBP1 account in part for P4's action in human granulosa/luteal cells.

PMID- 16984988
TI  - Randomized, double-blind, placebo-controlled trial of long-acting release
      octreotide for treatment of Graves' ophthalmopathy.
AB  - CONTEXT: Despite a strong rationale for trials of somatostatin analogs in the
      treatment of Graves' ophthalmopathy (GO), recent studies have provided
      conflicting results. OBJECTIVE: The objective of the study was to determine
      whether octreotide long-acting release (LAR) is effective treatment for active
      GO. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled
      study. SETTING: The setting was a single tertiary referral center. PATIENTS:
      Twenty-nine consecutive euthyroid patients with active GO [clinical activity
      score (CAS) >or= 3] were enrolled; 25 completed the study. INTERVENTION: Patients
      received four monthly doses of either octreotide LAR (20 mg) or saline by im
      injections. MAIN OUTCOME MEASURES: Primary measure was a change in CAS; the
      secondary measure was changes in retrobulbar tissue volume, proptosis, lid
      fissure width, range of motion, and diplopia fields. RESULTS: Median (range) CAS
      change was 2.5 (1, 5) in the treatment and 1.0 (0, 7) in the placebo group (P =
      0.02). Median lid fissure width improved in the treatment group, (decreased 1 mm
      on the right and 0.5 mm on the left), compared with the placebo group (no change
      on the right, P < 0.01; increased 1 mm on the left, P < 0.01). No other
      significant differences between groups were identified. CONCLUSIONS: CAS improved
      to a greater extent in octreotide-LAR-treated patients than the control group.
      However, this finding may not represent clinical benefit because patients with
      higher baseline CAS were overrepresented in the treatment group, and the control
      group was small. In contrast, treatment-related improvement in eyelid fissure
      width was noted, suggesting that octreotide LAR may be useful in the treatment of
      a subgroup of active GO patients with significant lid retraction.

PMID- 16984989
TI  - Spontaneous hypothyroidism in adult women is predicted by small body size at
      birth and during childhood.
AB  - BACKGROUND: The relationships of early growth with coronary heart disease and
      type 2 diabetes have received considerable attention. It is not known whether
      fetal or childhood growth is linked with autoimmune disorders. OBJECTIVE: Our
      objective was to assess whether the risk of adult-onset spontaneous
      hypothyroidism is predicted by body size at birth and during childhood. DESIGN
      AND SETTING: We conducted a birth cohort study in Helsinki, Finland.
      PARTICIPANTS: A total of 293 women who were born between 1934 and 1944 and had
      their heights and weights recorded at birth and during childhood participated in
      the study. MEASUREMENTS: We measured spontaneous hypothyroidism, defined as: 1) a
      disease history confirmed from medical records, or 2) previously undiagnosed
      hypothyroidism (TSH > 10 mU/liter). RESULTS: Twenty women (6.8%) had spontaneous
      hypothyroidism; 18 had been diagnosed previously, between 43 and 65 yr of age,
      and two had undiagnosed subclinical hypothyroidism. In addition, 59 women were
      thyroid peroxidase antibody positive. Compared with the 214 thyroid peroxidase
      antibody-negative women with no thyroid disorder, those with spontaneous
      hypothyroidism had on average 252 g [95% confidence interval (CI), 61 to 443 g; P
      = 0.01] lower birth weight and 1.2 cm (95% CI, 0.5 to 2.0 cm; P = 0.002) shorter
      length at birth. The odds of developing hypothyroidism increased 4.4-fold per
      kilogram decrease in birth weight (95% CI, 1.4 to 14.1). Hypothyroid subjects had
      been shorter in early childhood and had lower body mass index during later
      childhood. CONCLUSIONS: Small body size at birth and during childhood increases
      the risk of spontaneous hypothyroidism in adult women.

PMID- 16984991
TI  - High molecular weight, rather than total, adiponectin levels better reflect
      metabolic abnormalities associated with childhood obesity.
AB  - CONTEXT: Japanese are prone to obesity-induced metabolic derangement, which is
      linked to serum adipocytokine profile even in children. OBJECTIVE: The objective
      of the study was to determine whether high molecular-weight adiponectin (H-Adn)
      more specifically relates to metabolic derangement in obese children than total
      adiponectin (T-Adn). DESIGN AND SETTING: A case (n = 59) control (n = 28) study
      was performed at the pediatric clinic of a university hospital. PATIENTS:
      Japanese obese children (38 boys and 21 girls) were consecutively enrolled. The
      ages ranged from 5 to 15 (10.3 +/- 0.3; mean +/- sem) yr. Nonobese children (15
      boys and 13 girls) were assigned as age-matched controls. MAIN OUTCOME MEASURES:
      Serum adiponectin multimeric complexes were assayed by an ELISA kit. The
      relationship of adiponectin to metabolic abnormalities was evaluated. RESULTS: T
      Adn (5.1 +/- 0.2 vs. 8.8 +/- 0.4 microg/ml), H-Adn (1.3 +/- 0.1 vs. 4.8 +/- 0.4
      microg/ml), and medium molecular weight-Adn were significantly lower in obese
      than in control children. After adjustment for age and sex, both T- and H-Adn
      were inversely correlated with insulin and homeostasis model of assessment
      insulin resistance, whereas H-Adn (but not T-Adn) inversely correlated with
      visceral fat area, as determined by computed tomography. Seven obese children
      were estimated to have metabolic syndrome and showed selective decrease in H-Adn
      and H/T-Adn. CONCLUSION: H-Adn reflects metabolic abnormalities due to obesity
      better than T-Adn in children. H-Adn is associated with the development of
      metabolic syndrome, even in childhood.

PMID- 16984990
TI  - Beta-adrenergic and atrial natriuretic peptide interactions on human
      cardiovascular and metabolic regulation.
AB  - CONTEXT: Atrial natriuretic peptide (ANP) has well-known cardiovascular effects
      and modifies lipid and carbohydrate metabolism in humans. OBJECTIVE: The
      objective of the study was to determine the metabolic and cardiovascular
      interaction of beta-adrenergic receptors and ANP. DESIGN: This was a crossover
      study, conducted 2004-2005. SETTING: The study was conducted at an academic
      clinical research center. PATIENTS: PATIENTS included 10 healthy young male
      subjects (body mass index 24 +/- 1 kg/m2). INTERVENTION: We infused iv
      incremental ANP doses (6.25, 12.5, and 25 ng/kg.min) with and without propranolol
      (0.20 mg/kg in divided doses followed by 0.033 mg/kg.h infusion). Metabolism was
      monitored through venous blood sampling, im, and sc microdialysis and indirect
      calorimetry. Cardiovascular changes were monitored by continuous
      electrocardiogram and beat-by-beat blood pressure recordings. MAIN OUTCOME
      MEASURES: Venous nonesterified fatty acid, glycerol, glucose, and insulin; and
      microdialysate glucose, glycerol, lactate, and pyruvate were measured. RESULTS:
      ANP increased heart rate dose dependently. beta-Adrenergic receptor blockade
      abolished the response. ANP elicited a dose-dependent increase in serum
      nonesterified fatty acid and glycerol concentrations. The response was not
      suppressed with propranolol. Venous glucose and insulin concentrations increased
      with ANP, both without or with propranolol. ANP induced lipid mobilization in sc
      adipose tissue. In skeletal muscle, microdialysate lactate increased, whereas the
      lactate to pyruvate ratio decreased, both with and without propranolol. Higher
      ANP doses increased lipid oxidation, whereas energy expenditure remained
      unchanged. Propranolol tended to attenuate the increase in lipid oxidation.
      CONCLUSIONS: Selected cardiovascular ANP effects are at least partly mediated by
      beta-adrenergic receptor stimulation. ANP-induced changes in lipid mobilization
      and glycolysis are mediated by another mechanism, presumably stimulation of
      natriuretic peptide receptors, whereas substrate oxidation might be modulated
      through adrenergic mechanisms.

PMID- 16984992
TI  - Four novel missense mutations in the CYP21A2 gene detected in Russian patients
      suffering from the classical form of congenital adrenal hyperplasia:
      identification, functional characterization, and structural analysis.
AB  - CONTEXT: Congenital adrenal hyperplasia is a group of autosomal recessive
      inherited disorders of steroidogenesis. The most frequent cause is the deficiency
      of steroid 21-hydroxylase (CYP21) due to mutations in the CYP21A2 gene.
      OBJECTIVE: We analyzed the functional and structural consequences of the four
      CYP21A2 missense mutations (C169R, G178R, W302R, and R426C) to prove their
      clinical relevance and study their impact on CYP21 function. RESULTS: Analyzing
      the mutations in vitro revealed an almost absent or negligible CYP21 activity for
      the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to
      deoxycorticosterone. Protein translation and intracellular localization were not
      affected by the mutants, as could be demonstrated by Western blotting and
      immunofluorescence studies. Analysis of these mutants in a three-dimensional
      model structure of the CYP21 protein explained the observed in vitro effects
      because all the mutations severely interfere either directly or indirectly with
      important structures of the 21-hydroxylase protein. CONCLUSION: The in vitro
      expression analysis of residual enzyme function is a complementary method to
      genotyping and an important tool for improving the understanding of the clinical
      phenotype of 21-hydroxylase deficiency. This forms the foundation for accurate
      clinical and genetic counseling and for prenatal diagnosis and treatment.
      Moreover, this report demonstrates that the combination of in vitro enzyme
      analysis and molecular modeling can yield novel insights into CYP450 structure
      functional relationships.

PMID- 16984993
TI  - Clinical review: Controversies regarding transdermal androgen therapy in
      postmenopausal women.
AB  - CONTEXT: Recently, the field of androgen therapy in postmenopausal women has
      received much attention and press. Although the ovary ceases to produce follicles
      and estrogen at menopause, it continues to produce androgens. Hence, many
      oophorectomized women complain of sexual dysfunction (despite adequate
      estrogenization). Previous studies of nontransdermal testosterone replacement
      have shown an improvement in libido and sexual frequency, although at the cost of
      supraphysiological testosterone levels. Transdermal testosterone patch (Intrinsa)
      was developed to deliver a physiological amount of testosterone. In 2004, the
      Food and Drug Administration voted not to approve Intrinsa until long-term safety
      data are available. EVIDENCE ACQUISITION: Recent trials of Intrinsa in
      postmenopausal women were included. A MEDLINE search was conducted for articles
      published over the last 40 yr based on the key words androgen therapy/replacement
      and postmenopausal women. Relevant placebo-controlled trials of nontransdermal
      androgen therapy in postmenopausal women were also reviewed. EVIDENCE SYNTHESIS:
      Early results from industry-funded trials show that transdermal testosterone
      therapy results in only moderate (although statistically significant) improvement
      in libido in surgically menopausal women (on estrogen). However, the published
      data are of short duration (24 wk). Hence, long-term safety in these women
      remains unclear. CONCLUSION: We recommend a short-term trial (not to exceed 24
      wk) of transdermal testosterone therapy (once approved) in surgically menopausal
      (estrogenized) women with distressful sexual dysfunction. Until the patch gets
      approval, a short trial of oral methyltestosterone in deserving estrogenized
      women may be justified.

PMID- 16984994
TI  - Expression and localization of delta-, kappa-, and mu-opioid receptors in human
      spermatozoa and implications for sperm motility.
AB  - CONTEXT: Endogenous opioid peptides signal through delta-, kappa-, and mu-opioid
      receptors. Some of these peptides such as endorphins and enkephalins are present
      in the male reproductive tract, but the presence of the corresponding receptors
      in human sperm cells has not yet been reported. OBJECTIVE: Our objective was to
      study the expression and localization of delta-, kappa-, and mu-opioid receptors
      on human spermatozoa and the implication in sperm motility. METHODS: The
      expression of receptors was studied by RT-PCR, Western blot, and
      immunofluorescence techniques. We evaluated the effects of activation of each
      opioid receptor by specific agonist and antagonist. RESULTS: Human spermatozoa
      express delta-, kappa-, and mu-opioid receptors. These receptors were located in
      different parts of the head, in the middle region, and in the tail of the sperm.
      Progressive motility of spermatozoa, an important parameter to evaluate male
      fertility, was found to be significantly reduced after incubation with the mu
      receptor agonist morphine, whereas this effect was antagonized in the presence of
      the corresponding antagonist naloxone. The delta-receptor antagonist naltrindole
      significantly reduced progressive motility immediately after its addition.
      However, the delta-receptor agonist DPDPE had no significant effect. Finally,
      neither the kappa-receptor agonist U50488 nor its antagonist nor-binaltorphimine
      significantly affected the progressive motility of human spermatozoa. CONCLUSION:
      We report for first time the presence of functional delta-, kappa-, and mu-opioid
      receptors in human sperm membranes. These findings are indicative of a role for
      the opioid system in the regulation of sperm physiology.

PMID- 16984995
TI  - McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary
      radiotherapy and/or pegvisomant in somatostatin analog-resistant patients.
AB  - BACKGROUND: Acromegaly, which may be present in patients with McCune-Albright
      syndrome (MCAS), in association with cafe-au-lait spots, precocious puberty, and
      fibrous dysplasia, is often difficult to treat surgically because skull base bone
      dysplasia prevents the removal of the pituitary adenoma. Somatostatin analogs
      (SAs) generally give only partial responses. The use of radiotherapy (RT) is
      controversial because of a possible risk of bone sarcomatous transformation. AIM:
      This study was a retrospective analysis of the efficacy and adverse effects of
      different treatment modalities in six patients with both MCAS and acromegaly.
      PATIENTS AND METHODS: Because surgery was impossible and SA failed to normalize
      GH/IGF-I hypersecretion, five of the six patients received fractionated RT (45-55
      Grays). Three patients (two with previous RT) were also prescribed pegvisomant.
      We analyzed the clinical features of acromegaly, GH, and IGF-I concentrations and
      bone radiological features. RESULTS: GH and IGF-I concentrations fell after RT
      (median follow-up, 5 yr; range, 0.5-9 yr). Symptoms of acromegaly improved in
      parallel. Bone sarcomatous transformation was only noted in one patient in a
      region (the mandible) outside the radiation field. RT alone and/or combined with
      SA failed to normalize GH/IGF-I levels in the five patients concerned. In
      contrast, IGF-I levels normalized very rapidly (5-9 months) in the three patients
      receiving pegvisomant (10-20 mg/d). CONCLUSION: RT may be an option for the
      treatment of acromegaly in patients with MCAS when surgery is impossible and SA
      therapy is ineffective. However, although no bone sarcomatous transformation was
      observed within the radiation field in this series, this risk cannot be ruled
      out. As shown in this small series of severely affected patients, pegvisomant
      therapy may thus be useful to normalize IGF-I levels rapidly.

PMID- 16984996
TI  - Tree-ring isotope records of tropical cyclone activity.
AB  - The destruction wrought by North Atlantic hurricanes in 2004 and 2005
      dramatically emphasizes the need for better understanding of tropical cyclone
      activity apart from the records provided by meteorological data and historical
      documentation. We present a 220-year record of oxygen isotope values of alpha
      cellulose in longleaf pine tree rings that preserves anomalously low isotope
      values in the latewood portion of the ring in years corresponding with known 19th
      and 20th century landfalling/near-coastal tropical storms and hurricanes. Our
      results suggest the potential for a tree-ring oxygen isotope proxy record of
      tropical cyclone occurrence extending back many centuries based on remnant pine
      wood from protected areas in the southeastern U.S.

PMID- 16984997
TI  - Characterization of brain neurons that express enzymes mediating neurosteroid
      biosynthesis.
AB  - Allopregnanolone (ALLO) and tetrahydrodeoxycorticosterone (THDOC) are potent
      positive allosteric modulators of GABA action at GABA(A) receptors. ALLO and
      THDOC are synthesized in the brain from progesterone or deoxycorticosterone,
      respectively, by the sequential action of two enzymes: 5alpha-reductase (5alpha
      R) type I and 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). This study
      evaluates 5alpha-R type I and 3alpha-HSD mRNA expression level in mouse brain by
      using in situ hybridization combined with glutamic acid decarboxylase 67/65,
      vesicular glutamate transporter 2, glial fibrillary acidic protein, and S100beta
      immunohistochemistry. We demonstrate that 5alpha-R type I and 3alpha-HSD
      colocalize in cortical, hippocampal, and olfactory bulb glutamatergic principal
      neurons and in some output neurons of the amygdala and thalamus. Neither 5alpha-R
      type I nor 3alpha-HSD mRNAs are expressed in S100beta- or glial fibrillary acidic
      protein-positive glial cells. Using glutamic acid decarboxylase 67/65 antibodies
      to mark GABAergic neurons, we failed to detect 5alpha-R type I and 3alpha-HSD in
      cortical and hippocampal GABAergic interneurons. However, 5alpha-R type I and
      3alpha-HSD are significantly expressed in principal GABAergic output neurons,
      such as striatal medium spiny, reticular thalamic nucleus, and cerebellar
      Purkinje neurons. A similar distribution and cellular location of
      neurosteroidogenic enzymes was observed in rat brain. Taken together, these data
      suggest that ALLO and THDOC, which can be synthesized in principal output
      neurons, modulate GABA action at GABA(A) receptors, either with an autocrine or a
      paracrine mechanism or by reaching GABA(A) receptor intracellular sites through
      lateral membrane diffusion.

PMID- 16984998
TI  - Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular
      NY-ESO-1-specific immune responses in cancer patients.
AB  - NY-ESO-1 is a cancer/testis antigen expressed in a range of human malignancies,
      and a number of vaccine strategies targeting NY-ESO-1 are being developed. In the
      present study, the safety and immunogenicity of recombinant vaccinia-NY-ESO-1 and
      recombinant fowlpox-NY-ESO-1 were analyzed in a series of 36 patients with a
      range of different tumor types. Each construct was first tested individually at
      two different dose levels and then in a prime-boost setting with recombinant
      vaccinia-NY-ESO-1 followed by recombinant fowlpox-NY-ESO-1. The vaccines were
      well tolerated either individually or together. NY-ESO-1-specific antibody
      responses and/or specific CD8 and CD4 T cell responses directed against a broad
      range of NY-ESO-1 epitopes were induced by a course of at least four vaccinations
      at monthly intervals in a high proportion of patients. CD8 T cell clones derived
      from five vaccinated patients were shown to lyse NY-ESO-1-expressing melanoma
      target cells. In several patients with melanoma, there was a strong impression
      that the natural course of the disease was favorably influenced by vaccination.

PMID- 16984999
TI  - Crystal structure and activities of EXPB1 (Zea m 1), a beta-expansin and group-1
      pollen allergen from maize.
AB  - Expansins are small extracellular proteins that promote turgor-driven extension
      of plant cell walls. EXPB1 (also called Zea m 1) is a member of the beta-expansin
      subfamily known in the allergen literature as group-1 grass pollen allergens.
      EXPB1 induces extension and stress relaxation of grass cell walls. To help
      elucidate expansin's mechanism of wall loosening, we determined the structure of
      EXPB1 by x-ray crystallography to 2.75-A resolution. EXPB1 consists of two
      domains closely packed and aligned so as to form a long, shallow groove with
      potential to bind a glycan backbone of approximately 10 sugar residues. The
      structure of EXPB1 domain 1 resembles that of family-45 glycoside hydrolase
      (GH45), with conservation of most of the residues in the catalytic site. However,
      EXPB1 lacks a second aspartate that serves as the catalytic base required for
      hydrolytic activity in GH45 enzymes. Domain 2 of EXPB1 is an Ig-like beta
      sandwich, with aromatic and polar residues that form a potential surface for
      polysaccharide binding in line with the glycan binding cleft of domain 1. EXPB1
      binds to maize cell walls, most strongly to xylans, causing swelling of the cell
      wall. Tests for hydrolytic activity by EXPB1 with various wall polysaccharides
      proved negative. Moreover, GH45 enzymes and a GH45-related protein called
      "swollenin" lacked wall extension activity comparable to that of expansins. We
      propose a model of expansin action in which EXPB1 facilitates the local movement
      and stress relaxation of arabinoxylan-cellulose networks within the wall by
      noncovalent rearrangement of its target.

PMID- 16985000
TI  - Engineering broad root-knot resistance in transgenic plants by RNAi silencing of
      a conserved and essential root-knot nematode parasitism gene.
AB  - Secreted parasitism proteins encoded by parasitism genes expressed in esophageal
      gland cells mediate infection and parasitism of plants by root-knot nematodes
      (RKN). Parasitism gene 16D10 encodes a conserved RKN secretory peptide that
      stimulates root growth and functions as a ligand for a putative plant
      transcription factor. We used in vitro and in vivo RNA interference approaches to
      silence this parasitism gene in RKN and validate that the parasitism gene has an
      essential function in RKN parasitism of plants. Ingestion of 16D10 dsRNA in vitro
      silenced the target parasitism gene in RKN and resulted in reduced nematode
      infectivity. In vivo expression of 16D10 dsRNA in Arabidopsis resulted in
      resistance effective against the four major RKN species. Because no known natural
      resistance gene has this wide effective range of RKN resistance, bioengineering
      crops expressing dsRNA that silence target RKN parasitism genes to disrupt the
      parasitic process represents a viable and flexible means of developing novel
      durable RKN-resistant crops and could provide crops with unprecedented broad
      resistance to RKN.

PMID- 16985001
TI  - Cryptic messages: is noncoagulant tissue factor reserved for cell signaling?

PMID- 16985002
TI  - Mapping land use of tropical regions from space.

PMID- 16985003
TI  - Large-scale analysis of ion channel gene expression in the mouse heart during
      perinatal development.
AB  - The immature and mature heart differ from each other in terms of excitability,
      action potential properties, contractility, and relaxation. This includes
      upregulation of repolarizing K(+) currents, an enhanced inward rectifier K(+)
      (Kir) current, and changes in Ca(2+), Na(+), and Cl(-) currents. At the molecular
      level, the developmental regulation of ion channels is scantily described. Using
      a large-scale real-time quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) assay, we performed a comprehensive analysis of ion channel
      transcript expression during perinatal development in the embryonic (embryonic
      day 17.5), neonatal (postnatal days 1-2), and adult Swiss-Webster mouse hearts.
      These data are compared with publicly available microarray data sets
      (Cardiogenomics project). Developmental mRNA expression for several transcripts
      was consistent with the published literature. For example, transcripts such as
      Kir2.1, Kir3.1, Nav1.5, Cav1.2, etc. were upregulated after birth, whereas others
      [e.g., Ca(2+)-activated K(+) (KCa)2.3 and minK] were downregulated. Cl(-) channel
      transcripts were expressed at higher levels in immature heart, particularly those
      that are activated by intracellular Ca(2+). Defining alterations in the ion
      channel transcriptome during perinatal development will lead to a much improved
      understanding of the electrophysiological alterations occurring in the heart
      after birth. Our study may have important repercussions in understanding the
      mechanisms and consequences of electrophysiological alterations in infants and
      may pave the way for better understanding of clinically relevant events such as
      congenital abnormalities, cardiomyopathies, heart failure, arrhythmias, cardiac
      drug therapy, and the sudden infant death syndrome.

PMID- 16985005
TI  - Differential brain transcriptome of beta4 nAChR subunit-deficient mice: is it the
      effect of the null mutation or the background strain?
AB  - Studies using mice with beta4 nicotinic acetylcholine receptor (nAChR) subunit
      deficiency (beta4-/- mice) helped reveal the roles of this subunit in
      bradycardiac response to vagal stimulation, nicotine-induced seizure activity and
      anxiety. To identify genes that might be related to beta4-containing nAChRs
      activity, we compared the mRNA expression profiles of brains from beta4-/- and
      wild-type mice using Affymetrix U74Av2 microarray. Seventy-seven genes
      significantly differentiated between these two experimental groups. Of them, the
      two most downregulated were spastic paraplegia 21 (human) homolog (Spg21) and 6
      pyruvoyl-tetrahydropterin synthase (Pts) genes. Since the targeted mutagenesis of
      the beta4 nAChR subunit was done by using two mouse strains, 129SvEv and
      C57BL/6J, it is possible that the genes closely linked to the mutated beta4 gene
      represent the 129SvEv allele and not the control C57BL/6J-driven allele. We
      examined this possibility by using public database and quantitative RT-PCR. The
      expression levels of Spg21 and Pts genes that, like the beta4 gene, are localized
      on mouse chromosome 9, as well as the expression levels of other genes located on
      this chromosome, were dependent on the mouse background strain. The 67
      differentially expressed genes that are not located on chromosome 9 were further
      analyzed for overrepresented functional annotations and transcription regulatory
      elements compared with the entire microarray. Genes encoding for proteins
      involved in tyrosine phosphatase activity, calcium ion binding, cell growth
      and/or maintenance, and chromosome organization were overrepresented. Our data
      enhance the understanding of the molecular interactions involved in the beta4
      nAChR subunit function. They also emphasize the need for careful interpretation
      of expression microarray studies done on genetically manipulated animals.

PMID- 16985004
TI  - Potential regulatory relationship between the nested gene DDC8 and its host gene
      tissue inhibitor of metalloproteinase-2.
AB  - Nested genes are fairly common within the mammalian nervous system, yet few
      studies have examined whether the guest and host genes might be coordinately
      regulated. Tissue inhibitors of metalloproteinase (TIMPs) inhibit extracellular
      matrix proteolysis mediated by metzincin proteases. TIMP-2 is the only TIMP not
      nested within a synapsin gene. It does, however, serve as a host for differential
      display clone 8 (DDC8), a testis-specific gene whose expression is upregulated
      during spermatogenesis. Here, we demonstrate that DDC8 is not testis specific.
      Furthermore, DDC8 expression in nonneural and neural tissues mimics that of TIMP
      2, including its upregulation in response to traumatic brain injury, suggesting a
      potential regulatory relationship. The most striking observation is that the TIMP
      2 knockout mouse brain contains TIMP-2 mRNA encoding exons 2-5, which are
      downstream of DDC8, but not exon 1, which contains the signal sequence and
      cysteine residue required for MMP inhibition, indicating a functional knockout.
      That TIMP-2 transcripts in wild-type brain contain DDC8 sequence suggests
      alternative splicing between the two genes.

PMID- 16985006
TI  - Microarray interrogation of human metanephric mesenchymal cells highlights
      potentially important molecules in vivo.
AB  - Many molecules have been implicated in kidney development, often based on
      experimental animal studies with organ cultures and cell lines. There are very
      few studies, however, that have directly addressed equivalent living human
      embryonic tissues. We generated renal mesenchymal cell lines from normal human
      metanephroi and used a microarray strategy to define changes in gene expression
      after stimulation with growth factors which enhance nephrogenesis in rodents.
      Changes were observed in 1) genes modulating diverse general cellular processes,
      such as matrix metalloproteinase 1 and stanniocalcin 1; 2) genes previously
      implicated in organogenesis e.g., sprouty 4 and midline 1; and 3) genes involved
      in blood vessel growth, including angiopoietin 1 and 4. Expression of these same
      genes was subsequently confirmed in vivo. Our novel data have identified several
      previously unhighlighted genes that may be implicated in differentiation programs
      within early human nephrogenesis.

PMID- 16985007
TI  - Novel method for high-throughput phenotyping of sleep in mice.
AB  - Assessment of sleep in mice currently requires initial implantation of chronic
      electrodes for assessment of electroencephalogram (EEG) and electromyogram (EMG)
      followed by time to recover from surgery. Hence, it is not ideal for high
      throughput screening. To address this deficiency, a method of assessment of sleep
      and wakefulness in mice has been developed based on assessment of
      activity/inactivity either by digital video analysis or by breaking infrared
      beams in the mouse cage. It is based on the algorithm that any episode of
      continuous inactivity of > or =40 s is predicted to be sleep. The method gives
      excellent agreement in C57BL/6J male mice with simultaneous assessment of sleep
      by EEG/EMG recording. The average agreement over 8,640 10-s epochs in 24 h is 92%
      (n = 7 mice) with agreement in individual mice being 88-94%. Average EEG/EMG
      determined sleep per 2-h interval across the day was 59.4 min. The estimated mean
      difference (bias) per 2-h interval between inactivity-defined sleep and EEG/EMG
      defined sleep was only 1.0 min (95% confidence interval for mean bias -0.06 to
      +2.6 min). The standard deviation of differences (precision) was 7.5 min per 2-h
      interval with 95% limits of agreement ranging from -13.7 to +15.7 min. Although
      bias significantly varied by time of day (P = 0.0007), the magnitude of time-of
      day differences was not large (average bias during lights on and lights off was
      +5.0 and -3.0 min per 2-h interval, respectively). This method has applications
      in chemical mutagenesis and for studies of molecular changes in brain with
      sleep/wakefulness.

PMID- 16985008
TI  - Review of microarray experimental design strategies for genetical genomics
      studies.
AB  - Genetical genomics approaches provide a powerful tool for studying the genetic
      mechanisms governing variation in complex traits. By combining information on
      phenotypic traits, pedigree structure, molecular markers, and gene expression,
      such studies can be used for estimating heritability of mRNA transcript
      abundances, for mapping expression quantitative trait loci (eQTL), and for
      inferring regulatory gene networks. Microarray experiments, however, can be
      extremely costly and time consuming, which may limit sample sizes and statistical
      power. Thus it is crucial to optimize experimental designs by carefully choosing
      the subjects to be assayed, within a selective profiling approach, and by
      cautiously controlling systematic factors affecting the system. Also, a rigorous
      strategy should be used for allocating mRNA samples across assay batches, slides,
      and dye labeling, so that effects of interest are not confounded with nuisance
      factors. In this presentation, we review some selective profiling strategies for
      genetical genomics studies, including the selection of individuals for increased
      genetic dissimilarity and for a higher number of recombination events. Efficient
      designs for studying epistasis are also discussed, as well as experiments for
      inferring heritability of transcriptional levels. It is shown that solving an
      optimal design problem generally requires a numerical implementation and that the
      optimality criteria should be intimately related to the goals of the experiment,
      such as the estimation of additive, dominance, and interacting effects,
      localizing putative eQTL, or inferring genetic and environmental variance
      components associated with transcriptional abundances.

PMID- 16985009
TI  - A gene coexpression network for bovine skeletal muscle inferred from microarray
      data.
AB  - We present the application of large-scale multivariate mixed-model equations to
      the joint analysis of nine gene expression experiments in beef cattle muscle and
      fat tissues with a total of 147 hybridizations, and we explore 47 experimental
      conditions or treatments. Using a correlation-based method, we constructed a gene
      network for 822 genes. Modules of muscle structural proteins and enzymes,
      extracellular matrix, fat metabolism, and protein synthesis were clearly evident.
      Detailed analysis of the network identified groupings of proteins on the basis of
      physical association. For example, expression of three components of the z-disk,
      MYOZ1, TCAP, and PDLIM3, was significantly correlated. In contrast, expression of
      these z-disk proteins was not highly correlated with the expression of a cluster
      of thick (myosins) and thin (actin and tropomyosins) filament proteins or of
      titin, the third major filament system. However, expression of titin was itself
      not significantly correlated with the cluster of thick and thin filament proteins
      and enzymes. Correlation in expression of many fast-twitch muscle structural
      proteins and enzymes was observed, but slow-twitch-specific proteins were not
      correlated with the fast-twitch proteins or with each other. In addition, a
      number of significant associations between genes and transcription factors were
      also identified. Our results not only recapitulate the known biology of muscle
      but have also started to reveal some of the underlying associations between and
      within the structural components of skeletal muscle.

PMID- 16985010
TI  - Cytokine mRNA profiling of peripheral blood mononuclear cells from
      trypanotolerant and trypanosusceptible cattle infected with Trypanosoma
      congolense.
AB  - To examine differences in cytokine profiles that may confer
      tolerance/susceptibility to bovine African trypanosomiasis, N'Dama
      (trypanotolerant, n = 8) and Boran (trypanosusceptible, n = 8) cattle were
      experimentally challenged with Trypanosoma congolense. Blood samples were
      collected over a 34-day period, and RNA was extracted from peripheral blood
      mononuclear cells. The expression levels of a panel of 14 cytokines were profiled
      over the time course of infection and between breeds. Messenger RNA (mRNA)
      transcript levels for the IL2, IL8, and IL1RN genes were significantly
      downregulated across the time course of infection in both breeds. There was an
      early increase in transcripts for genes encoding proinflammatory mediators (IFNG,
      IL1A, TNF, and IL12) in N'Dama by 14 days postinfection (dpi) compared with
      preinfection levels that was not detected in the susceptible Boran breed. By the
      time of peak parasitemia, a type 2 helper T cells (T(H)2)-like cytokine
      environment was prevalent that was particularly evident in the Boran. Increases
      in transcripts for the IL6 (29 and 34 dpi) and IL10 (21, 25, and 29 dpi) genes
      were detected that were higher in the Boran compared with N'Dama. These findings
      highlight the implications for using murine models to study the bovine immune
      response to trypanosomiasis, where in some cases cytokine expression patterns
      differ. Overall, these data suggest that the trypanotolerant N'Dama are more
      capable of responding very early in infection with proinflammatory and T(H)1 type
      cytokines than the trypanosusceptible Boran and may explain why N'Dama control
      parasitemia more efficiently than Boran during the early stages of infection.

PMID- 16985011
TI  - Conquering cancer disparities: new opportunities for cancer epidemiology,
      biomarker, and prevention research.

PMID- 16985012
TI  - Biorepository and biospecimen science: a new focus for CEBP.

PMID- 16985013
TI  - Sample collection, processing, and storage for large-scale studies:
      biorepositories to support cancer research.

PMID- 16985014
TI  - Establishing a cancer center data bank and biorepository for multidisciplinary
      research.
AB  - The establishment of a biorepository with linkage to clinical and epidemiologic
      data will provide an invaluable resource for cancer research, including studies
      of cancer etiology, progression, and prognosis, as well as development of
      biomarkers for early detection. Developing an infrastructure for a biorepository
      linked to clinical, pathologic, and epidemiologic data requires significant
      efforts in strategic planning for efficient means to ascertain, identify, and
      consent participants, as well as guidelines for blood collection, processing, and
      storage while maintaining participant privacy rights. In this report, we present
      an approach to developing a Data Bank and Biorepository at our own institution,
      with discussion of elements to be considered when establishing such a bank.

PMID- 16985015
TI  - Collection, processing, and storage of biological samples in epidemiologic
      studies: sex hormones, carotenoids, inflammatory markers, and proteomics as
      examples.
AB  - The measurement of biomarkers in blood specimens has become an integral component
      of many epidemiologic studies and introduces several decision points about
      specimen collection, processing, and storage for the investigator. We briefly
      discuss the current state of knowledge for four commonly assessed biomarkers:
      estrogens and other sex hormones, ascorbic acid and carotenoids, cytokines
      involved in the inflammatory response, and proteomics. Sex hormones are
      relatively robust to type of sample collected, delayed processing (if chilled),
      and long-term storage at <-70 degrees C. Ascorbic acid and carotenoids also are
      relatively robust to sample type and delayed processing (if chilled); however,
      the blood sample should not be exposed to sunlight and must be stored at <-70
      degrees C to prevent substantial degradation. If ascorbic acid is of primary
      interest, an acid stabilizer should be added during processing. Less is known for
      cytokines and proteomics, although initial research suggests that these assays
      are sensitive to varying collection, processing, and storage methods. Overall, we
      recommend conducting pilot studies if any nonstandard collection, processing, or
      storage procedure is used. Finally, decisions about these issues depend primarily
      on the scientific questions of most interest, cost, flexibility, and resources.

PMID- 16985016
TI  - Blood collection, shipment, processing, and storage.
AB  - As part of the AACR Annual Meeting Methods Workshop "Sample Collection,
      Processing, and Storage for Large-Scale Studies: Biorepositories to Support
      Cancer Research," blood specimen collection, processing, storage, and
      dissemination issues were discussed. Whole blood and blood fractions comprise a
      major portion of biospecimen collections for population-based studies. Although
      procedures for collecting, processing, storing, and shipping blood components are
      generally standardized and well documented, several important factors need to be
      considered before a new study involving blood collection is initiated. Blood is
      collected from study participants for a variety of purposes, including as a
      source of DNA, and for a variety of laboratory analyses that may be done on whole
      blood or blood fractions, including serum, plasma, and lymphocytes. Blood or
      blood fractions may be shipped to laboratories and biorepositories either at
      ambient temperature, cooled or frozen, depending on the intended analyses. Blood
      processing may include fractionation, cryopreservation to preserve the viability
      of lymphocytes, or purification of nucleic acids. The proper storage conditions
      depend on a variety of factors, including the intended analyses and whether the
      specimens will be used within a short period or need to be stored for longer
      periods. As for all laboratory and biorepository procedures, blood collection,
      shipment, processing, and storage should be conducted under a strict quality
      assurance program, including standard operating procedures and regular quality
      control reviews.

PMID- 16985017
TI  - Approaches to DNA/RNA Extraction and whole genome amplification.
AB  - Analysis of DNA and/or RNA is an important component of most epidemiologic
      studies. The methods used for their preparation vary depending on the number of
      samples in the study as well as the amount of tissue or cells available, the
      specific downstream assay, and the resources available. They range from classic
      phenol/chloroform extractions to robotic methods suitable for large-scale
      studies. Several methods are also available for the quantitation of DNA/RNA,
      including UV or fluorescence measurements and PCR. For DNA samples of limited
      quantity, it is also now possible to use whole genome amplification to increase
      the amount of DNA suitable for genotyping. Finally, a major issue in quality
      control is the careful labeling and handling of samples.

PMID- 16985018
TI  - Effect of a 12-month exercise intervention on patterns of cellular proliferation
      in colonic crypts: a randomized controlled trial.
AB  - BACKGROUND: Colon crypt architecture and proliferation may be appropriate
      biomarkers for testing prevention interventions. A hypothesized mechanism for
      exercise-induced colon cancer risk reduction might be through alterations in
      colon crypt cell architecture and proliferation. METHODS: Healthy, sedentary
      participants with a colonoscopy within the previous 3 years were recruited
      through gastroenterology practices and media. We randomly assigned 100 women and
      102 men, ages 40 to 75 years, to a control group or a 12-month exercise
      intervention of moderate-to-vigorous aerobic exercise, 60 minutes per day, 6 days
      per week, and assessed change in number and relative position of Ki67-stained
      cells in colon mucosal crypts. RESULTS: Exercisers did a mean 370 min/wk (men)
      and 295 min/wk (women) of exercise (seven dropped the intervention). In men, the
      mean height of Ki67-positive nuclei relative to total crypt height was related to
      amount of exercise, with changes from baseline of 0.0% (controls), +0.3%
      (exercisers <250 min/wk), -1.7% (exercisers 250-300 min/wk), and -2.4%
      (exercisers >300 min/wk; P(trend) = 0.03). In male exercisers whose
      cardiopulmonary fitness (V(O(2))max) increased >5%, the mean height of Ki67
      positive nuclei decreased by 2% versus 0.9% in other exercisers, and versus no
      change in controls (P(trend) = 0.05). Similar trends were observed in other
      proliferation markers. In women, increased amount of exercise or V(O(2))max did
      not result in notable changes in proliferation markers. CONCLUSIONS: A 12-month
      moderate-to-vigorous intensity aerobic exercise intervention resulted in
      significant decreases in colon crypt cell proliferation indices in men who
      exercised a mean of >/=250 min/wk or whose V(O(2))max increased by >/=5%.

PMID- 16985019
TI  - Proteomic profiling identifies cyclooxygenase-2-independent global proteomic
      changes by celecoxib in colorectal cancer cells.
AB  - Celecoxib, a selective inhibitor of the enzyme cyclooxygenase-2 (COX-2), has been
      shown to be a promising chemoprevention agent. The chemopreventive efficacy of
      celecoxib is believed to be a consequence of its COX-2-dependent and COX-2
      independent effects on a variety of cellular processes including proliferation,
      apoptosis, angiogenesis, and immunosurveillance. In an attempt to identify
      proteomic markers modulated by celecoxib that are independent of its inhibitory
      effect on COX-2, the colorectal cancer cell line HCT-116, a nonexpresser of COX
      2, was treated with celecoxib. We used the powerful, state-of-the-art two
      dimensional difference gel electrophoresis technology coupled with mass
      spectrometric sequencing to compare global proteomic profiles of HCT-116 cells
      before and after treatment with celecoxib. Among the differentially expressed
      proteins identified following celecoxib treatment were proteins involved in
      diverse cellular functions including glycolysis, protein biosynthesis, DNA
      synthesis, mRNA processing, protein folding, phosphorylation, redox regulation,
      and molecular chaperon activities. Our study presents a comprehensive analysis of
      large-scale celecoxib-modulated proteomic alterations, at least some of which may
      be mechanistically related to the COX-2-independent chemopreventive effect of
      celecoxib.

PMID- 16985020
TI  - Folate metabolism polymorphisms influence risk of colorectal adenoma recurrence.
AB  - Folate intake is inversely related to risk of developing colorectal neoplasia.
      Associations between risk of colorectal neoplasia and polymorphisms in genes
      coding for enzymes involved in folate metabolism have also been reported,
      suggesting a relationship between genotype and development of colorectal
      neoplasia. To further investigate the effects of folate metabolism genotypes on
      colorectal neoplasia, we genotyped 546 patients participating in a randomized
      controlled trial of folate supplementation for the prevention of colorectal
      adenoma recurrence. A significantly reduced risk of recurrence was observed in
      patients heterozygous for the MTRR A66G polymorphism [relative risk (RR), 0.64;
      95% confidence interval (95% CI), 0.46-0.90] or heterozygous for the MTHFR A1298C
      polymorphism (RR, 0.71; 95% CI, 0.52-0.97). Furthermore, a significant reduction
      in recurrence risk was seen in MTRR A66G heterozygotes who received folate
      supplements but not in those who did not receive folate. Patients heterozygous
      for the MTHFR C677T polymorphism had a nonsignificant risk reduction (RR, 0.92;
      95% CI, 0.69-1.23), as did patients with one or two variant alleles for the MTR
      A2756G polymorphism (RR, 0.82; 95% CI, 0.60-1.12). No influence on recurrence
      risk was observed for the TSER, TSER 3R G>C, and TS 1494del6 variants. These
      findings provide additional support for the hypothesis that germ line variants in
      folate metabolism genes influence the development of colorectal adenomas.

PMID- 16985021
TI  - Polymorphisms in nucleotide excision repair genes and DNA repair capacity
      phenotype in sisters discordant for breast cancer.
AB  - Interindividual differences in DNA repair capacity (DRC) may play a critical role
      in breast cancer risk. Previously, we determined that DRC measured via removal of
      in vitro-induced benzo[a]pyrene diolepoxide-DNA adducts in lymphoblastoid cell
      lines was lower in cases compared with controls among sisters discordant for
      breast cancer from the Metropolitan New York Registry of Breast Cancer Families.
      We have now determined genotypes for seven single nucleotide polymorphisms in
      five nucleotide excision repair genes, including Xeroderma pigmentosum
      complementation group A (XPA +62T>C), group C (XPC Lys939Gln and Ala499Val),
      group D (XPD Asp312Asn and Lys751Gln), and group G (XPG His1104Asp) and ERCC1
      (8092 C>A) in a total of 160 sister pairs for whom DRC phenotype data were
      available. Overall, there were no statistically significant differences in
      average DRC for most of the genotypes. A final multivariate conditional logistic
      model, including three single nucleotide polymorphisms (XPA +62T>C, XPC
      Ala499Val, and XPG His1104Asp) and smoking status, only modestly predicted DRC
      after adjusting for case-control status and age of blood donation. The overall
      predictive accuracy was 61% in the model with a sensitivity of 78% and
      specificity of 39%. These findings suggest that those polymorphisms we have
      investigated to date in nucleotide excision repair pathway genes explain only a
      small amount of the variability in DRC.

PMID- 16985022
TI  - Estrogens, enzyme variants, and breast cancer: a risk model.
AB  - Oxidative metabolites of estrogens have been implicated in the development of
      breast cancer, yet relatively little is known about the metabolism of estrogens
      in the normal breast. We developed a mathematical model of mammary estrogen
      metabolism based on the conversion of 17beta-estradiol (E(2)) by the enzymes
      cytochrome P450 (CYP) 1A1 and CYP1B1, catechol-O-methyltransferase (COMT), and
      glutathione S-transferase P1 into eight metabolites [i.e., two catechol
      estrogens, 2-hydroxyestradiol (2-OHE(2)) and 4-hydroxyestradiol (4-OHE(2)); three
      methoxyestrogens, 2-methoxyestradiol, 2-hydroxy-3-methoxyestradiol, and 4
      methoxyestradiol; and three glutathione (SG)-estrogen conjugates, 2-OHE(2)-1-SG,
      2-OHE(2)-4-SG, and 4-OHE(2)-2-SG]. When used with experimentally determined rate
      constants with purified enzymes, the model provides for a kinetic analysis of the
      entire metabolic pathway. The predicted concentration of each metabolite during a
      30-minute reaction agreed well with the experimentally derived results. The model
      also enables simulation for the transient quinones, E(2)-2,3-quinone (E(2)-2,3-Q)
      and E(2)-3,4-quinone (E(2)-3,4-Q), which are not amenable to direct quantitation.
      Using experimentally derived rate constants for genetic variants of CYP1A1,
      CYP1B1, and COMT, we used the model to simulate the kinetic effect of enzyme
      polymorphisms on the pathway and identified those haplotypes generating the
      largest amounts of catechols and quinones. Application of the model to a breast
      cancer case-control population identified a subset of women with an increased
      risk of breast cancer based on their enzyme haplotypes and consequent E(2)-3,4-Q
      production. This in silico model integrates both kinetic and genomic data to
      yield a comprehensive view of estrogen metabolomics in the breast. The model
      offers the opportunity to combine metabolic, genetic, and lifetime exposure data
      in assessing estrogens as a breast cancer risk factor.

PMID- 16985023
TI  - Genomic instability and prognosis in breast carcinomas.
AB  - BACKGROUND: We recently reported that DNA content of breast adenocarcinomas,
      cytometrically assessed by diploid (D), tetraploid (T), and aneuploid (A)
      categories, can be further divided into genomically stable and unstable subtypes
      by means of the stemline scatter index (SSI). The aim of the present study was to
      survey the clinical correlates and the prognostic value of the SSI in a
      consecutive series of 890 breast cancer patients. RESULTS: Genomically stable
      subtype had a significantly better survival compared with the unstable subtype
      within each ploidy category: D (P = 0.04), T (P = 0.008), and A (P = 0.004). By
      contrast, no statistically significant difference in survival was observed
      between the D, T, and A categories within the stable (P = 0.23) and unstable
      subtypes (P = 0.12). Among A tumors, the unstable subtype tended to be larger,
      more frequently estrogen- and progesterone-receptor negative, and to be of higher
      grade compared with the stable subtype. Stable D tumors tended to have lower
      grade than the unstable subtype, but among the D and T tumors, genomic
      instability was not associated with receptor status. Within the Elston grade 3,
      lymph node-positive or estrogen receptor-positive subgroups, patients with stable
      tumors had significantly better survival compared with unstable tumors (P = 0.01,
      0.002, and 7.2E-5, respectively). CONCLUSIONS: The SSI contributes supplementary
      biological and clinical information in addition to ploidy information alone.
      Objective classification of breast adenocarcinomas into stable and unstable
      subtypes is a useful prognostic indicator independent of established clinical
      factors.

PMID- 16985024
TI  - Endometrial cancer risk is associated with variants of the mismatch repair genes
      MLH1 and MSH2.
AB  - Women with germ-line mutations in the mismatch repair genes (responsible for
      hereditary nonpolyposis colorectal cancer) face an increased risk of colonic and
      endometrial cancer. However, these germ-line mutations are rare and are
      responsible for fewer than 1% of endometrial cancers. Therefore, we examined
      whether or not common variants of the hereditary nonpolyposis colorectal cancer
      associated genes might also be associated with an increased risk of endometrial
      cancer. Three single-nucleotide polymorphisms were selected in the MLH1 and MSH2
      mismatch repair genes. All the various 672 women with endometrial cancer and 880
      controls were genotyped. Each of these three single-nucleotide polymorphisms was
      associated with an increased risk of endometrial cancer. Carriers of the MLH1 nt
      93 A allele were at a 1.5-fold increased risk of developing endometrial cancer
      compared with controls [95% confidence interval (95% CI), 1.2-2.0; P = 0.001].
      The risk was higher for homozygote carriers [odds ratio (OR), 1.9; 95% CI, 1.2
      3.2; P = 0.009]. For carriers of the MSH2 rs2303428 C allele, the OR was 1.4 (95%
      CI, 1.0-1.9; P = 0.05), and for carriers of the MSH2 rs2059520 G allele, the OR
      was 1.3 (95% CI, 1.0-1.7; P = 0.03). More than 9% of endometrial cancer cases
      carried a variant allele in both MLH1 and MSH2. For these women, the risk of
      endometrial cancer was particularly high (OR, 2.1; 95% CI, 1.2-3.6; P = 0.005).
      For patients younger than 50 years at diagnosis who carried both variants, the
      risk was even higher (OR, 3.4; 95% CI, 1.7-6.6; P = 0.0005). In summary, two
      common variant alleles of the MLH1 and MSH2 genes make a substantial contribution
      to endometrial cancer incidence in Ontario.

PMID- 16985025
TI  - Evaluation of apolipoprotein A1 and posttranslationally modified forms of
      transthyretin as biomarkers for ovarian cancer detection in an independent study
      population.
AB  - BACKGROUND: Although overall 5-year survival rates for ovarian cancer are poor
      (10-30%), stage I/IIa patients have a 95% 5-year survival. New biomarkers that
      improve the diagnostic performance of existing tumor markers are critically
      needed. A previous study by Zhang et al. reported identification and validation
      of three biomarkers using proteomic profiling that together improved early-stage
      ovarian cancer detection. METHODS: To evaluate these markers in an independent
      study population, postdiagnostic/pretreatment serum samples were collected from
      women hospitalized at the Mayo Clinic from 1980 to 1989 as part of the National
      Cancer Institute Immunodiagnostic Serum Bank. Sera from 42 women with ovarian
      cancer, 65 with benign tumors, and 76 with digestive diseases were included in
      this study. Levels of various posttranslationally forms of transthyretin and
      apolipoprotein A1 were measured in addition to CA125. RESULTS: Mean levels of
      five of the six forms of transthyretin were significantly lower in cases than in
      controls. The specificity of a model including transthyretin and apolipoprotein
      A1 alone was high [96.5%; 95% confidence interval (95% CI), 91.9-98.8%] but
      sensitivity was low (52.4%; 95% CI, 36.4-68.0%). A class prediction algorithm
      using all seven markers, CA125, and age maintained high specificity (94.3%; 95%
      CI, 89.1-97.5%) but had higher sensitivity (78.6%; 95% CI, 63.2-89.7%).
      CONCLUSIONS: We were able to replicate the findings reported by Zhang et al. in
      an independently conducted blinded study. These results provide some evidence
      that including age of patient and these markers in a model may improve
      specificity, especially when CA125 levels are >/=35 units/mL. Influences of
      sample handling, subject characteristics, and other covariates on biomarker
      levels require further consideration in discovery and replication or validation
      studies.

PMID- 16985026
TI  - Metabolic gene variants and risk of non-Hodgkin's lymphoma.
AB  - Genes involved in metabolism of environmental chemical exposures exhibit sequence
      variability that may mediate the risk of non-Hodgkin's lymphoma. We evaluated
      associations between non-Hodgkin's lymphoma and 15 variants in AHR, CYP1A1,
      CYP1A2, CYP1B1, CYP2C9, CYP2E1, GSTP1, GSTM3, EPHX1, NQO1, and PON1. Cases were
      identified from four Surveillance, Epidemiology, and End Results registries in
      the United States, and population-based controls were identified through random
      digit dialing and Medicare eligibility files. Metabolic gene variants were
      characterized for the 1,172 (89% of total) cases and 982 (93%) controls who
      provided biological samples for genotyping. Subjects who were heterozygous or
      homozygous for the cytochrome P450 gene variant CYP1B1 V432L G allele were at
      slightly greater risk of non-Hodgkin's lymphoma [odds ratio (OR), 1.27; 95%
      confidence interval (95% CI), 0.97-1.65]; these results were consistent across B
      cell lymphoma subtypes and among both non-Hispanic White and Black subjects,
      although not statistically significant. The CYP2E1 -1054T allele was associated
      with decreased risk of non-Hodgkin's lymphoma (CT and TT genotypes combined OR,
      0.59; 95% CI, 0.37-0.93), and this pattern was observed among all histologic
      subtypes. The numbers of cases of particular subtypes were rather small for
      stable estimates, but we noted that the PON1 L55M AA allele, associated with
      slightly increased risk of non-Hodgkin's lymphoma (variant homozygotes OR, 1.36;
      95% CI, 0.96-1.95), was most strongly associated with follicular non-Hodgkin's
      lymphoma and T-cell lymphoma, with ORs for variant homozygotes of 2.12 and 2.93,
      respectively. There was no overall association with non-Hodgkin's lymphoma for
      the other gene variants we examined. The modest effects we observed may reflect
      the context of exposures within the general population represented in our study.

PMID- 16985027
TI  - Consumption of aspartame-containing beverages and incidence of hematopoietic and
      brain malignancies.
AB  - BACKGROUND: In a few animal experiments, aspartame has been linked to
      hematopoietic and brain cancers. Most animal studies have found no increase in
      the risk of these or other cancers. Data on humans are sparse for either cancer.
      Concern lingers regarding this widely used artificial sweetener. OBJECTIVE: We
      investigated prospectively whether aspartame consumption is associated with the
      risk of hematopoietic cancers or gliomas (malignant brain cancer). METHODS: We
      examined 285,079 men and 188,905 women ages 50 to 71 years in the NIH-AARP Diet
      and Health Study cohort. Daily aspartame intake was derived from responses to a
      baseline self-administered food frequency questionnaire that queried consumption
      of four aspartame-containing beverages (soda, fruit drinks, sweetened iced tea,
      and aspartame added to hot coffee and tea) during the past year. Histologically
      confirmed incident cancers were identified from eight state cancer registries.
      Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were
      estimated using Cox proportional hazards regression that adjusted for age, sex,
      ethnicity, body mass index, and history of diabetes. RESULTS: During over 5 years
      of follow-up (1995-2000), 1,888 hematopoietic cancers and 315 malignant gliomas
      were ascertained. Higher levels of aspartame intake were not associated with the
      risk of overall hematopoietic cancer (RR for >/=600 mg/d, 0.98; 95% CI, 0.76
      1.27), glioma (RR for >/=400 mg/d, 0.73; 95% CI, 0.46-1.15; P for inverse linear
      trend = 0.05), or their subtypes in men and women. CONCLUSIONS: Our findings do
      not support the hypothesis that aspartame increases hematopoietic or brain cancer
      risk.

PMID- 16985028
TI  - Maternal supplement, micronutrient, and cured meat intake during pregnancy and
      risk of medulloblastoma during childhood: a children's oncology group study.
AB  - We conducted a case-control study of medulloblastoma/primitive neuroectodermal
      tumors of brain (PNET) to pursue findings related to vitamin and mineral
      supplements, micronutrients, and cured meat consumption during gestation. Mothers
      of 315 cases ages <6 years at diagnosis in 1991 to 1997 identified from the
      United States and Canada through the Children's Oncology Group and mothers of 315
      controls selected by random-digit dialing were interviewed. In the periconception
      period of the index pregnancy, case mothers were less likely than control mothers
      to report use of multivitamins [adjusted odds ratio (OR), 0.7; 95% confidence
      interval (95% CI), 0.4-1.0; P = 0.08] and to be in the highest quartile of iron
      and folate intake from food and supplements combined (adjusted OR for iron, 0.5;
      95% CI, 0.3-0.9; P(trend) = 0.008; adjusted OR for folate, 0.5; 95% CI, 0.3-0.9;
      P(trend) = 0.007). Case and control mothers had similar intakes of cured meats,
      although case mothers were more likely to have the combination of high cured meat
      and low vitamin C intake (OR, 1.5; 95% CI, 1.0-2.3; P = 0.08). The results of the
      study add to the evidence of a protective role for multivitamins, suggest a
      possible role for micronutrients early in pregnancy, and generally do not support
      an association between cured meats and medulloblastoma/PNET.

PMID- 16985029
TI  - Familiality in Barrett's esophagus, adenocarcinoma of the esophagus, and
      adenocarcinoma of the gastroesophageal junction.
AB  - BACKGROUND AND AIM: The familial aggregation of Barrett's esophagus,
      adenocarcinoma of the esophagus, and adenocarcinoma of the gastroesophageal
      junction, jointly termed familial Barrett's esophagus, may represent a complex
      genetic trait. The aim of this study was to determine the proportion of patients
      with these diseases who have familial Barrett's esophagus. METHODS: Information
      on gastroesophageal reflux symptoms, known risk factors for Barrett's esophagus,
      and family history of Barrett's esophagus and cancers, was collected at six
      hospitals using a structured questionnaire from probands with either long-segment
      Barrett's esophagus, adenocarcinoma of the esophagus, or adenocarcinoma of the
      gastroesophageal junction. Family history of Barrett's esophagus or esophageal
      cancer in a first- or second-degree relative was determined by reviewing medical
      records of all relatives reported to be affected. RESULTS: Seventy one of 411
      (17.3%) probands reported an affected first- and/or second-degree relative. Upon
      review of medical records of the reportedly affected relatives, familial
      Barrett's esophagus was definitively determined in the case of 30 (7.3%) probands
      comprising 17 of 276 (6.2%) with Barrett's esophagus, 11 of 116 (9.5%) with
      adenocarcinoma of the esophagus, and 2 of 21 (9.5%) with adenocarcinoma of the
      gastroesophageal junction. The diagnosis in the relative reported by the proband
      to be affected was found not to be Barrett's esophagus or adenocarcinoma in 15
      (3.6%) cases. The diagnosis could not be determined in 26 (6.3%) cases in which
      the proband reported an affected relative. There were no significant differences
      in age of disease onset, gender, race, or gastroesophageal reflux symptoms
      between definitive familial Barrett's esophagus probands and nonfamilial
      probands. CONCLUSION: Familial Barrett's esophagus can be confirmed in 7.3% of
      persons presenting with Barrett's esophagus, adenocarcinoma of the esophagus, or
      adenocarcinoma of the gastroesophageal junction.

PMID- 16985030
TI  - Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms and
      gastric cancer: a meta-analysis.
AB  - BACKGROUND: Polymorphisms of interleukin-1B (IL1B) and its receptor antagonist
      (IL1RN) genes have been inconsistently associated with gastric cancer risk. We
      examined these associations by performing meta-analyses. MATERIALS AND METHODS:
      Twenty-five studies testing the association between IL1B and/or IL1RN gene
      polymorphisms and gastric cancer were examined: 14 studies of IL1B-511, 14
      studies of IL1B-31, 8 studies of IL1B+3954, and 23 studies of IL1RN. Overall and
      ethnicity-specific summary odds ratios and corresponding 95% confidence intervals
      for gastric cancer associated with these polymorphisms were estimated using fixed
      and random-effects models. Heterogeneity and publication bias were evaluated.
      RESULTS: IL1B-511T and IL1RN*2 were associated with gastric cancer risk in
      Caucasians, but not in Asians. For IL1B-511T, the association in Caucasians was
      stronger when intestinal-subtype and noncardia gastric cancer cases were
      examined. A nonsignificant trend was observed between IL1B-31C and gastric cancer
      in Caucasians. No significant association of IL1B+3954T and gastric cancer risk
      was detected. Studies with better methodologic characteristics reported stronger
      effects. There was no evidence of publication bias. CONCLUSION: IL1B-511T is
      associated with gastric cancer susceptibility in Caucasians. The meta-analyses
      suggest that the conflicting results among studies may be explained by variation
      in allele frequencies among the ethnic groups and variation in tumor types, as
      well as by the methodologic quality of the studies.

PMID- 16985031
TI  - Vitamin D intake and the risk for pancreatic cancer in two cohort studies.
AB  - Vitamin D and its analogues exhibit potent antitumor effects in many tissues,
      including the pancreas. Normal and malignant pancreatic tissues were recently
      shown to express high levels of vitamin D 1-alpha-hydroxylase, which converts
      circulating 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D. We examined
      associations between dietary intake of vitamin D, calcium, and retinol and
      subsequent risk for pancreatic cancer. We conducted prospective studies in
      cohorts of 46,771 men ages 40 to 75 years as of 1986 (the Health Professionals
      Follow-up Study), and 75,427 women ages 38 to 65 years as of 1984 (the Nurses'
      Health Study), documenting incident pancreatic cancer through the year 2000. Diet
      was ascertained by semiquantitative food-frequency questionnaire. We identified
      365 incident cases of pancreatic cancer over 16 years of follow-up. Compared with
      participants in the lowest category of total vitamin D intake (<150 IU/d), pooled
      multivariate relative risks for pancreatic cancer were 0.78 [95% confidence
      interval (95% CI), 0.59-1.01] for 150 to 299 IU/d, 0.57 (95% CI, 0.40-0.83) for
      300 to 449 IU/d, 0.56 (95% CI, 0.36-0.87) for 450 to 599 IU/d, and 0.59 (95% CI,
      0.40-0.88) for >/=600 IU/d (P(trend) = 0.01). These associations may be stronger
      in men than women. After adjusting for vitamin D intake, calcium and retinol
      intakes were not associated with pancreatic cancer risk. In two U.S. cohorts,
      higher intakes of vitamin D were associated with lower risks for pancreatic
      cancer. Our results point to a potential role for vitamin D in the pathogenesis
      and prevention of pancreatic cancer.

PMID- 16985032
TI  - Use of analgesics and nonsteroidal anti-inflammatory drugs, genetic
      predisposition, and bladder cancer risk in Spain.
AB  - BACKGROUND: We assessed use of nonaspirin nonsteroidal anti-inflammatory drugs
      (NSAID), aspirin, paracetamol (acetaminophen), phenacetin, and metamizol
      (dipyrone) and risk of bladder cancer and their interaction with polymorphisms in
      drug-metabolizing genes. METHODS: We analyzed personal interview data from 958
      incident bladder cancer cases and 1,029 hospital controls from a multicenter case
      control study in Spain. A drug matrix was developed to estimate cumulative
      lifetime dose of active ingredients. Polymorphisms in GSTP1, SULT1A1, CYP2E1,
      CYP2C9, and NAT2 were examined. RESULTS: A significant reduction in bladder
      cancer risk [adjusted odds ratio (OR), 0.4; 95% confidence interval (95% CI), 0.2
      0.9] was observed for regular users of nonaspirin NSAIDs compared with never
      users. Regular users of aspirin experienced no reduction in risk (OR, 1.0; 95%
      CI, 0.7-1.5). Regular users of paracetamol had no overall increased risk of
      bladder cancer (OR, 0.8; 95% CI, 0.4-1.3), but our data suggested a qualitative
      interaction with the GSTP1 I105V genotype. Subjects with at least one copy of the
      359L or 144C variant alleles in the NSAID-metabolizing gene CYP2C9 had a slightly
      decreased risk of bladder cancer (OR, 0.8; 95% CI, 0.7-1.0; P = 0.037); however,
      having at least one copy of the 359L or 144C variant alleles did not
      significantly modify the protective effect of nonaspirin NSAID use. CONCLUSION:
      Regular use of nonaspirin NSAIDs was associated with a reduced risk of bladder
      cancer, which was not modified by polymorphisms in the NSAID-metabolizing gene
      CYP2C9. We found no evidence of an overall effect for paracetamol or aspirin use.

PMID- 16985033
TI  - Association of polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 genes with levels
      of DNA damage in peripheral blood lymphocytes among coke-oven workers.
AB  - Accumulating evidence has shown that both DNA damage caused by the metabolites of
      polycyclic aromatic hydrocarbons (PAH) and genetic polymorphisms in PAH-metabolic
      genes contribute to individual susceptibility to PAH-induced carcinogenesis.
      However, the functional relevance of genetic polymorphisms in PAH-metabolic genes
      in exposed individuals is still unclear. In this study of 240 coke-oven workers
      (the exposed group) and 123 non-coke-oven workers (the control group), we
      genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and GSTT1 genes by PCR
      methods, and determined the levels of DNA damage in peripheral blood lymphocytes
      using the alkaline comet assay. We found that the ln-transformed Olive tail
      moment (Olive TM) values in the exposed group were significantly higher than
      those in the control group (P < 0.001). Furthermore, in the exposed group, the
      Olive TM values in subjects with the AhR Lys(554) variant genotype were higher
      than those with the AhR Arg(554)/Arg(554) genotype (P = 0.021). Similarly, the
      Olive TM values in the non-coke-oven workers with the CYP1A1 MspI CC + CT
      genotype were lower than the values of those with the CYP1A1 MspI TT genotype (P
      = 0.005). However, these differences were not evident for GSTM1 and GSTT1. These
      results suggested that the polymorphism of AhR might modulate the effects of PAHs
      in the exposed group; however, the underlying molecular mechanisms by which this
      polymorphism may have affected the levels of PAH-induced DNA damage warrant
      further investigation.

PMID- 16985034
TI  - Prevalence of fragile histidine triad expression in tumors from saudi arabia: a
      tissue microarray analysis.
AB  - AIM: The fragile histidine triad (FHIT) gene was discovered and proposed as a
      tumor suppressor gene for most human cancers. It encodes the most active common
      human chromosomal fragile region, FRA3B. We studied the prevalence of loss of
      FHIT expression in various tumors and correlated its loss with various
      clinicopathologic features. METHODS: To determine whether the absence of FHIT
      expression correlates with clinical variables such as grade, stage, and survival
      time, we assessed FHIT expression using immunohistochemistry. More than 1,800
      tumors from more than 75 tumor categories were analyzed by immunohistochemistry
      in a tissue microarray format. RESULTS: Loss of FHIT expression ranged from 19%
      in ovarian tumors to 67% in lung cancers. Clinical and pathologic features like
      grade, stage, tumor size, and lymph node metastasis showed correlation with loss
      of FHIT expression in some tumors. No difference was seen in the survival
      patterns and loss of FHIT expression in any of the tumor groups studied.
      CONCLUSIONS: Loss of FHIT expression is an ubiquitous event in the multistep,
      multifactorial carcinogenesis process. FHIT may be altered at different stages in
      different types of cancers. Most of the tumors with a wider prevalence of loss of
      FHIT expression as an early event show a correlation with clinicopathologic
      features. However, in some of the tumors, FHIT expression is lost as a late event
      and is only seen in a fraction of the tumors.

PMID- 16985035
TI  - Immunohistochemical expressions of Ki-67, cyclin D1, beta-catenin, cyclooxygenase
      2, and epidermal growth factor receptor in human colorectal adenoma: a validation
      study of tissue microarrays.
AB  - BACKGROUND: Tissue microarray (TMA) holds promise as a high-throughput method for
      the analysis of biomarkers in tissue specimens. The validity and reliability of
      this method, however, may vary for different biomarkers in different tissue
      specimens. OBJECTIVES: In this study, we evaluated the validity and reliability
      of using TMA to assess biomarkers in colorectal adenomas. METHODS: Sixty-three
      consecutive patients with colorectal adenomas were recruited in this study. Two
      TMA blocks were constructed using four punches from each adenoma (one periphery,
      one deep, and two middle zones). The immunostaining of five markers (Ki-67,
      cyclin D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor)
      was analyzed, and the concordance between data obtained from TMAs and standard
      whole-tissue sections was evaluated by Spearman's correlation and kappa analysis.
      RESULTS: Colorectal adenoma exhibited zonal, heterogeneous expression patterns
      for all five markers. The concordance rates for the semiquantitative evaluation
      of markers between data from TMAs and whole sections ranged from 87% to 93% with
      corresponding kappa statistics of 77% to 90%. In addition, both quantitative and
      semiquantitative methods were used to score TMA sections, and good correlations
      between these two methods were shown for all five markers with intraclass
      correlation coefficients ranging from 0.5 to 0.8. CONCLUSION: Our study indicates
      that TMA can be used to reliably assess the expression levels of Ki-67, cyclin
      D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor in
      colorectal adenoma tissues.

PMID- 16985036
TI  - Up-to-date estimates of cancer patient survival even with common latency in
      cancer registration.
AB  - In an era of ongoing improvement in cancer patient survival, available long-term
      survival figures from cancer registries are often outdated and too pessimistic
      for two reasons: first, delay in availability of cancer registry data, typically
      in the order of a few years, and, second, application of cohort-based methods of
      survival analysis, which provide survival estimates for patients diagnosed many
      years ago. We developed a model-based period analysis approach aimed to overcome
      both problems. We provide extensive empirical evaluation of our approach by
      comparing its performance with that of previously available methods for
      monitoring of 5- and 10-year relative survival, with the use of data from the
      nationwide Finnish Cancer Registry of 490,279 patients ages >/=15 years and
      diagnosed with one of 20 common forms of cancer between 1953 and 1997. We show
      that, in most cases, the model-based approach predicts 5- and 10-year relative
      survival expectations of newly diagnosed patients quite closely and much better
      than any of the previously available methods, including standard period analysis.
      We conclude that the model-based approach may enable deriving up-to-date cancer
      survival rates even with the common latency in availability of cancer registry
      data.

PMID- 16985037
TI  - Serum heat shock protein 70 levels and lung cancer risk: a case-control study
      nested in a large cohort study.
AB  - Chronic inflammation contributes to the process of carcinogenesis, but few
      epidemiologic studies have examined associations with risk of lung cancer.
      Relationships between lung cancer risk and serum levels of both heat shock
      protein 70 (Hsp70) and high-sensitivity C-reactive protein (hsCRP) were
      investigated in a case-control study nested in the Japan Collaborative Cohort
      Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were
      collected at baseline from 39,242 men and women between 1988 and 1990. Of these,
      240 deaths from lung cancer were identified through 1999, and 569 controls were
      matched for sex, age, and study area. Serum levels were measured in 189 cases and
      377 controls for Hsp70 and in 209 cases and 425 controls for hsCRP. Odds ratios
      (95% confidence intervals) across quartiles, adjusted for confounding factors,
      including smoking habits, were 0.83 (0.44-1.58), 1.41 (0.77-2.60), and 1.84 (0.92
      3.71) for Hsp70 (P(trend) = 0.042) and 1.13 (0.67-1.91), 0.66 (0.38-1.16), and
      1.19 (0.70-2.02) for hsCRP (P(trend) = 0.941). In males, odds ratios (95%
      confidence intervals) across quartiles were 1.30 (0.59-2.84), 1.74 (0.83-3.67),
      and 2.49 (1.06-5.85) for Hsp70 (P(trend) = 0.029). High levels of serum Hsp70
      might thus be associated with increased risk of lung cancer among Japanese males,
      although further studies are needed to clarify associations between chronic
      inflammation and lung cancer.

PMID- 16985038
TI  - PGR +331 A/G and increased risk of epithelial ovarian cancer.
AB  - Childbearing and use of oral contraceptives are known to lower the risk of
      ovarian cancer, and it has been suggested that progesterone or progestin
      exposures play a role in these associations. The effects of progesterone may be
      mediated in part through the progesterone receptor, which exists in two
      functionally distinct protein isoforms, hPR-A and hPR-B. It is known that
      individuals carrying the A allele of the progesterone receptor gene (PGR)
      polymorphism, +331 A/G (rs10895068), have greater production of the hPR-B
      receptor isoform. We therefore examined the association between PGR +331 A/G
      genotype and risk of ovarian cancer in a population-based study of 490 cases and
      534 controls in the state of Connecticut. Adjusted for various reproductive and
      other factors, a statistically significant increased risk was seen for carriage
      of the A allele compared with GG genotype [odds ratio (OR), 1.68; 95% confidence
      interval (95% CI), 1.09-2.59]. When subjects were considered separately according
      to menopausal status, no increased risk with the A allele was seen for
      premenopausal women (OR, 0.96; 95% CI, 0.46-2.02) but significantly increased
      risk was found for postmenopausal women (OR, 2.31; 95% CI, 1.31-4.06). Similar
      increased risks particularly among postmenopausal women were seen for all
      histologic tumor types. These findings have been observed before for breast and
      endometrial cancer, although not for ovary, but still suggest that an hPR-B
      mechanism may be involved in ovarian neoplasia.

PMID- 16985039
TI  - Quality and quantity of saliva DNA obtained from the self-administrated oragene
      method--a pilot study on the cohort of Swedish men.
AB  - Self-collection of saliva has the potential to provide molecular epidemiologic
      studies with DNA in a user-friendly way. We evaluated the new Oragene saliva
      collection method and requested saliva samples by mail from 611 men (ages 53-87
      years). We obtained a response rate of, on average, 80% [varying from 89% (ages
      67-71 years) to 71% (ages 77-87 years)]. DNA was extracted from 90 randomly
      selected samples, and its usefulness was evaluated with respect to quality,
      quantity, and whole-genome amplification (WGA). Visual inspection of DNA on
      agarose gels showed high molecular weight DNA (>23 kb) and no degradation. Total
      DNA yield measured with PicoGreen ranged from 1.2 to 169.7 mug, with a mean of
      40.3 mug (SD, 36.5 mug) and a median of 29.4 mug. Human DNA yield was estimated
      by real-time PCR of the human prothrombin gene to account for 68% (SD, 20%) of
      total DNA. We did WGA on 81 saliva DNA samples by using the GenomiPhi DNA kit and
      genotyped both saliva DNA and WGA DNA for 10 single-nucleotide polymorphisms
      randomly selected from the human genome. Overall genotyping success rate was 96%
      for saliva DNA and 95% for WGA DNA; 79% of saliva DNA samples and 79% of WGA DNA
      samples were successfully genotyped for all 10 single-nucleotide polymorphisms.
      For the 10 specific assays, the success rates ranged between 88% and 100%. Almost
      complete genotypic concordance (99.7%) was observed between saliva DNA and WGA
      DNA. In conclusion, Oragene saliva DNA in this study collected from men is of
      high quality and can be used as an alternative to blood DNA in molecular
      epidemiologic studies.

PMID- 16985040
TI  - Personal permanent hair dye use is not associated with bladder cancer risk:
      evidence from a case-control study.
AB  - Whether personal hair dye use is associated with an increased bladder cancer risk
      has been controversial and there are limited available data addressing this
      issue. We used a large case-control study of 712 incident bladder cancer cases
      and 712 age-, gender-, and ethnicity-matched controls to evaluate this
      association. After adjusting for confounding variables, the use of permanent hair
      dye was not associated with bladder cancer risk in all subjects [odds ratio (OR),
      0.81; 95% confidence interval (95% CI), 0.50-1.30], in women (OR, 0.90; 95% CI,
      0.41-1.96), or in men (OR, 0.68; 95% CI, 0.36-1.29). The lack of association was
      not modified by duration of use, frequency of use, lifetime use, age at first
      use, or color of use in subsequent stratified analyses. Our data do not support
      personal hair dye use as an important risk factor for bladder cancer.

PMID- 16985042
TI  - Mammographic density, hormone therapy, and risk of breast cancer.

PMID- 16985043
TI  - Mesothelin is shed from tumor cells.

PMID- 16985045
TI  - Etiologic conclusions from similar birth cohort effects.

PMID- 16985046
TI  - Therapeutic value of glycosaminoglycans in cancer.
AB  - Glycosaminoglycans are unbranched polysaccharides composed of repeating units of
      alternating uronic acids and amino sugars. Most glycosaminoglycans are covalently
      attached to core proteins to form proteoglycans. Posttranslational modifications
      result in specific motifs that bind to a large variety of ligands, thus
      regulating growth factor signaling, cellular behavior, inflammation,
      angiogenesis, and the proteolytic environment. Dysregulated expression of
      glycosaminoglycans is present in cancer and reported to correlate with clinical
      prognosis in several malignant neoplasms. Recent knowledge on the biological
      roles of these molecules in cancer biology, tumor angiogenesis, and metastasis
      has promoted the development of drugs targeting them. Pharmaceutical approaches
      include the use of chemically modified heparins and glycosaminoglycans with
      defined structures, combination of inhibitors of glycosaminoglycan biosynthesis
      and polyamine depletion, and biologically active glycosaminoglycan-binding
      peptides. In addition, glycosaminoglycans are used as tumor-specific delivery and
      targeting vehicles for toxins and chemotherapeutics. Encouraging results in
      animal studies and clinical trials show the clinical relevance of
      glycosaminoglycan-based drugs and the use of glycosaminoglycans as therapeutic
      targets.

PMID- 16985047
TI  - Repression of cell cycle-related proteins by oxaliplatin but not cisplatin in
      human colon cancer cells.
AB  - Oxaliplatin (Eloxatin) is a third-generation platinum derivative with an in vitro
      and in vivo spectrum of activity distinct from that of cisplatin, especially in
      colon cancer cells. Here, we studied the molecular basis of this difference on
      the HCT-116 human colon carcinoma cell line (mismatch repair-deficient, wild-type
      functional p53). Oxaliplatin inhibited HCT-116 cell proliferation with greater
      efficacy than cisplatin. At comparable concentrations, cisplatin slowed down the
      replication phase and activated the G2-M checkpoint, whereas oxaliplatin
      activated the G1-S checkpoint and completely blocked the G2-M transition. With
      the aim of finding oxaliplatin-specific target genes and mechanisms differing
      from those of cisplatin, we established the transcriptional signatures of both
      products on HCT-116 cells using microarray technology. Based on hierarchical
      clustering, we found that (a) many more genes were modulated by oxaliplatin
      compared with cisplatin and (b) among the 117 modulated genes, 79 were regulated
      similarly by both drugs and, in sharp contrast, 38 genes were dose dependently
      down-regulated by oxaliplatin and, conversely, up-regulated or unaffected by
      cisplatin. Interestingly, several cell cycle-related genes encoding proteins
      involved in DNA replication and G2-M progression belong to this latter group. RNA
      modulations, confirmed at the protein level, were in accordance with oxaliplatin-
      and cisplatin-induced cell cycle variations. Beyond the identification of genes
      affected by both drugs, the identified oxaliplatin-specific target genes could be
      useful as predictive markers for evaluating and comparing the efficacy and
      molecular pharmacology of platinum drugs.

PMID- 16985048
TI  - The Rho kinase inhibitor fasudil inhibits tumor progression in human and rat
      tumor models.
AB  - The ability of cancer cells to undergo invasion and migration is a prerequisite
      for tumor metastasis. Rho, a Ras-related small GTPase, and the Rho-associated
      coiled coil-containing protein kinases (Rho kinases, ROCK1 and ROCK2) are key
      regulators of focal adhesion, actomyosin contraction, and thus cell motility.
      Inhibitors of this pathway have been shown to inhibit tumor cell motility and
      metastasis. Here, we show that fasudil [1-(5-isoquinolinesulfonyl)
      homopiperazine], an orally available inhibitor of Rho kinases, and its metabolite
      1-(hydroxy-5-isoquinoline sulfonyl-homopiperazine) (fasudil-OH) modify tumor cell
      morphology and inhibit tumor cell migration and anchorage-independent growth. In
      addition, we show that fasudil inhibited tumor progression in three independent
      animal models. In the MM1 peritoneal dissemination model, tumor burden and
      ascites production were reduced by > 50% (P < 0.05). In the HT1080 experimental
      lung metastasis model, fasudil decreased lung nodules by approximately 40% (P <
      0.05). In the orthotopic breast cancer model with MDA-MB-231, there were 3-fold
      more tumor-free mice in the fasudil-treated group versus saline control group (P
      < 0.01). Fasudil has been approved for the treatment of cerebral vasospasm and
      associated cerebral ischemic symptoms. In patients, fasudil is well tolerated
      without any serious adverse reactions. Therefore, the concept of Rho kinase
      inhibition as an antimetastatic therapy for cancer can now be clinically
      explored.

PMID- 16985049
TI  - Gene therapy with TRAIL against renal cell carcinoma.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis
      in cancer cells. However, TRAIL is not toxic against most normal cells. We have
      accordingly examined by in vivo electroporation whether TRAIL induces apoptosis
      in renal cell carcinoma. In addition, combination treatment with TRAIL and 5
      fluorouracil (5-FU) against renal cell carcinoma was also investigated. The NC65
      renal cell carcinoma line was used as a target. pCAGGS TRAIL was injected into
      the NC65 tumors in the right flanks of severe combined immunodeficient mice.
      Tumors were pulsed with the CUY21 electroporator. Electroporation was done once
      on day 0 or thrice on days 0, 2, and 4. Apoptosis was determined by terminal
      deoxyribonucleotide transferase-mediated nick-end labeling assay. When TRAIL gene
      therapy using in vivo i.t. electroporation was done once only, the growth of NC65
      tumors was not inhibited. However, when TRAIL gene therapy was done thrice,
      growth suppression of the NC65 tumors was observed. Transfection of the TRAIL
      gene by in vivo electroporation induced apoptosis in NC65 tumors. When NC65 cells
      were treated with TRAIL gene therapy in combination with 5-FU, stronger growth
      suppression was obtained. TRAIL gene therapy did not induce liver dysfunction in
      severe combined immunodeficient mice. This study shows that TRAIL gene therapy
      induced growth suppression and apoptosis in NC65 tumors without severe side
      effects, and that combination treatment of NC65 cells with TRAIL gene therapy and
      5-FU resulted in higher antitumor activity. These findings suggest that TRAIL
      gene therapy and/or 5-FU may be effective against renal cell carcinoma without
      harmful toxic effects.

PMID- 16985050
TI  - Cyclin D3 is down-regulated by rapamycin in HER-2-overexpressing breast cancer
      cells.
AB  - Rapamycin and its analogues are being tested as new antitumor agents. Rapamycin
      binds to FKBP-12 and this complex inhibits the activity of FRAP/mammalian target
      of rapamycin, which leads to dephosphorylation of 4EBP1 and p70 S6 kinase,
      resulting in blockade of translation initiation. We have found that RAP inhibits
      the growth of HER-2-overexpressing breast cancer cells. The phosphorylation of
      mammalian target of rapamycin, p70 S6 kinase, and 4EBP1 is inhibited by rapamycin
      and cells are arrested in the G1 phase, as determined by growth assays,
      fluorescence-activated cell sorting analysis, and bromodeoxyuridine incorporation
      studies. Rapamycin causes down-regulation of cyclin D3 protein, retinoblastoma
      hypophosphorylation, loss of cyclin-dependent kinase (cdk) 4, cdk6, and cdk2
      activity. The half-life of cyclin D3 protein decreases after rapamycin treatment,
      but not its synthesis, whereas the synthesis or half-life of cyclin D1 protein is
      not affected by the drug. Additionally, rapamycin caused accumulation of
      ubiquitinated forms of cyclin D3 protein, proteasome inhibitors blocked the
      effect of rapamycin on cyclin D3, and rapamycin stimulated the activity of the
      proteasome, showing that the effect of rapamycin on cyclin D3 is proteasome
      proteolysis dependent. This effect depends on the activity of HER-2 because
      Herceptin, a neutralizing antibody against HER-2, is able to block both the
      induction of proteasome activity and the cyclin D3 down-regulation due to
      rapamycin. Furthermore, inhibition of HER-2 gene expression by using small
      interfering RNA blocked the rapamycin effects on cyclin D3. These data indicate
      that rapamycin causes a G1 arrest in HER-2-overexpressing breast cancer cells
      that is associated with a differential destabilization and subsequent down
      regulation of cyclin D3 protein.

PMID- 16985051
TI  - Genetic alterations associated with acquired temozolomide resistance in SNB-19, a
      human glioma cell line.
AB  - Gliomas are highly lethal neoplasms that cannot be cured by currently available
      therapies. Temozolomide is a recently introduced alkylating agent that has
      yielded a significant benefit in the treatment of high-grade gliomas. However,
      either de novo or acquired chemoresistance occurs frequently and has been
      attributed to increased levels of O6-methylguanine-DNA methyltransferase or to
      the loss of mismatch repair capacity. However, very few gliomas overexpress O6
      methylguanine-DNA methyltransferase or are mismatch repair-deficient, suggesting
      that other mechanisms may be involved in the resistance to temozolomide. The
      purpose of the present study was to generate temozolomide-resistant variants from
      a human glioma cell line (SNB-19) and to use large-scale genomic and
      transcriptional analyses to study the molecular basis of acquired temozolomide
      resistance. Two independently obtained temozolomide-resistant variants exhibited
      no cross-resistance to other alkylating agents [1,3-bis(2-chloroethyl)-1
      nitrosourea and carboplatin] and shared genetic alterations, such as loss of a 2p
      region and loss of amplification of chromosome 4 and 16q regions. The karyotypic
      alterations were compatible with clonal selection of preexistent resistant cells
      in the parental SNB-19 cell line. Microarray analysis showed that 78 out of
      17,000 genes were differentially expressed between parental cells and both
      temozolomide-resistant variants. None are implicated in known resistance
      mechanisms, such as DNA repair, whereas interestingly, several genes involved in
      differentiation were down-regulated. The data suggest that the acquisition of
      resistance to temozolomide in this model resulted from the selection of less
      differentiated preexistent resistant cells in the parental tumor.

PMID- 16985052
TI  - Identification of novel small-molecule inhibitors of hypoxia-inducible factor-1
      transactivation and DNA binding.
AB  - Hypoxia-inducible factor-alpha (Hif-alpha) plays an important role in tumor
      growth by increasing resistance to apoptosis and the production of angiogenic
      factors, such as vascular endothelial growth factor (VEGF). Therefore, Hif-alpha
      is an attractive target for development of novel cancer therapeutics. We have
      generated Chinese hamster ovary cells, which stably express luciferase reporter
      construct under the control of a hypoxia response element to screen 15,000
      compounds. We identified 40 compounds that inhibited hypoxic up-regulation of
      luciferase, and the top 30 compounds were further screened in a secondary assay
      using MDA-468 breast cancer cell line. Eight compounds were shown to inhibit VEGF
      expression in hypoxic cells at subtoxic concentrations. Three top putative Hif
      inhibitors, DJ12, DJ15, and DJ30, were chosen for further analysis. Transient
      transfection of cells with hypoxia-regulated luciferase reporter plasmids further
      validated that these compounds inhibit hypoxia up-regulated genes. All three
      compounds failed to inhibit Hif-1alpha protein levels but they did inhibit
      induction of downstream targets of Hif-alpha under hypoxia. Two of the three
      compounds were cell type specific, whereas compound DJ12 inhibited VEGF at
      subtoxic levels in breast cancer cell lines MDA-468 and ZR-75, melanoma cell line
      MDA-435, and pVHL mutant renal cancer cell lines RCC4 and 786-0. Compound DJ12
      down-regulated mRNA of downstream targets of Hif-alpha, and significantly
      inhibited Hif-1alpha transactivation activity by blocking Hif-1alpha hypoxia
      response element-DNA binding. Our cell-based approach and deconvolution of the
      inhibitory effect of DJ12 has identified a novel compound that targets the
      hypoxia pathway by inhibiting Hif-alpha-inducible transcription.

PMID- 16985053
TI  - Valproate inhibition of histone deacetylase 2 affects differentiation and
      decreases proliferation of endometrial stromal sarcoma cells.
AB  - Covalent modifications of histone proteins, in particular deacetylation of lysine
      residues, are important for the regulation of gene transcription both in normal
      and malignant cells. These processes are controlled by histone acetyltransferases
      and histone deacetylases (HDAC) and have up to now not been described in solid
      mesenchymal tumors. The present study shows differences in the HDAC1 and HDAC2
      expression in endometrial stromal sarcomas (ESS) and a cognate cell line (ESS-1)
      compared with nonneoplastic endometrial stroma. We show for the first time that
      HDAC2 expression is consistently increased in ESS. In contrast, HDAC1 expression
      is generally lower than HDAC2 both in nonneoplastic stroma and in ESS, suggesting
      that these two proteins, although closely related, are regulated in different
      ways. In vitro experiments with an ESS cell line showed that valproate, an
      inhibitor of the class I HDACs, led to significant HDAC2 decrease and to cell
      differentiation. HDAC2 inhibition in ESS-1 cells caused significant changes in
      the cell cycle by inhibiting G1-S transition and influencing expression of
      p21WAF1 and cyclin D1. Moreover, in ESS-1 cells, increased expression of the
      p21WAF1 was associated with reduction of HDAC2 expression after transfection with
      small interfering RNA directed against HDAC2. Our results suggest that HDAC2
      might be considered as potential drug target in the therapy of ESS and that HDAC
      inhibitors should be further evaluated in clinical trials in ESS.

PMID- 16985054
TI  - Methotrexate enhances the antianabolic and antiproliferative effects of 5
      aminoimidazole-4-carboxamide riboside.
AB  - Because of its ability to mimic a low energy status of the cell, the cell
      permeable nucleoside 5-aminoimidazole-4-carboxamide (AICA) riboside was proposed
      as an antineoplastic agent switching off major energy-consuming processes
      associated with the malignant phenotype (lipid production, DNA synthesis, cell
      proliferation, cell migration, etc.). Key to the antineoplastic action of AICA
      riboside is its conversion to ZMP, an AMP mimetic that at high concentrations
      activates the AMP-activated protein kinase (AMPK). Here, in an attempt to
      increase the efficacy of AICA riboside, we pretreated cancer cells with
      methotrexate, an antimetabolite blocking the metabolism of ZMP. Methotrexate
      enhanced the AICA riboside-induced accumulation of ZMP and led to a decrease in
      the levels of ATP, which functions as an intrasteric inhibitor of AMPK.
      Consequently, methotrexate markedly sensitized AMPK for activation by AICA
      riboside and potentiated the inhibitory effects of AICA riboside on tumor
      associated processes. As cotreatment elicited antiproliferative effects already
      at concentrations of compounds that were only marginally effective when used
      alone, our findings on the cooperation between methotrexate and AICA riboside
      provide new opportunities both for the application of classic antimetabolic
      chemotherapeutics, such as methotrexate, and for the exploitation of the energy
      sensing machinery as a target for cancer intervention.

PMID- 16985055
TI  - Antiangiogenic activity of 4'-thio-beta-D-arabinofuranosylcytosine.
AB  - 4'-Thio-beta-D-arabinofuranosylcytosine (T-araC), a new-generation deoxycytidine
      nucleoside analogue, showed significant efficacy against numerous solid tumors in
      preclinical studies and entered clinical development for cancer therapy. It is a
      structural analogue of cytarabine (araC), a clinically used drug in the treatment
      of acute myelogenous leukemia, which has no or very limited efficacy against
      solid tumors. In comparison with araC, the excellent in vivo activity of T-araC
      against solid tumors suggests that, in addition to inhibition of DNA synthesis, T
      araC may target cellular signaling pathways, such as angiogenesis, in solid
      tumors. We studied T-araC and araC for their antiangiogenic activities in vitro
      and in vivo. Both compounds inhibited human endothelial cell proliferation with
      similar IC50s. However, only T-araC inhibited endothelial cell migration and
      differentiation into capillary tubules. T-araC also abrogated endothelial cell
      extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, a key signaling
      molecule involved in cellular processes of angiogenesis. Results from chick
      chorioallantoic membrane angiogenesis assays revealed that T-araC significantly
      inhibited the development of new blood vessels in vivo, whereas araC showed much
      less effect. The findings of this study show a role of T-araC in antiangiogenesis
      and suggest that T-araC combines antiproliferative and antiangiogenic activity in
      one molecule for a dual mechanism of drug action to achieve the excellent in vivo
      efficacy against several solid tumors. This study also provides important
      information for optimizing dosage and sequence of T-araC administration in
      clinical investigations by considering T-araC as both an antiproliferative and an
      antiangiogenic agent.

PMID- 16985056
TI  - 2-Methoxyestradiol suppresses microtubule dynamics and arrests mitosis without
      depolymerizing microtubules.
AB  - 2-Methoxyestradiol (2ME2), a metabolite of estradiol-17beta, is a novel
      antimitotic and antiangiogenic drug candidate in phase I and II clinical trials
      for the treatment of a broad range of tumor types. 2ME2 binds to tubulin at or
      near the colchicine site and inhibits the polymerization of tubulin in vitro,
      suggesting that it may work by interfering with normal microtubule function.
      However, the role of microtubule depolymerization in its antitumor mechanism of
      action has been controversial. To determine the mechanism by which 2ME2 induces
      mitotic arrest, we analyzed its effects on microtubule polymerization in vitro
      and its effects on dynamic instability both in vitro and in living MCF7 cells. In
      vitro, 2ME2 (5-100 micromol/L) inhibited assembly of purified tubulin in a
      concentration-dependent manner, with maximal inhibition (60%) at 200 micromol/L
      2ME2. However, with microtubule-associated protein-containing microtubules,
      significantly higher 2ME2 concentrations were required to depolymerize
      microtubules, and polymer mass was reduced by only 13% at 500 micromol/L 2ME2. In
      vitro, dynamic instability was inhibited at lower concentrations. Specifically, 4
      micromol/L 2ME2 reduced the mean growth rate by 17% and dynamicity by 27%. In
      living interphase MCF7 cells at the IC50 for mitotic arrest (1.2 micromol/L),
      2ME2 significantly suppressed the mean microtubule growth rate, duration and
      length, and the overall dynamicity, consistent with its effects in vitro, and
      without any observable depolymerization of microtubules. Taken together, the
      results suggest that the major mechanism of mitotic arrest at the lowest
      effective concentrations of 2ME2 is suppression of microtubule dynamics rather
      than microtubule depolymerization per se.

PMID- 16985057
TI  - Potential use of alexidine dihydrochloride as an apoptosis-promoting anticancer
      agent.
AB  - Despite advances in surgery, radiation, and chemotherapy, novel therapeutics are
      needed for head and neck cancer treatment. The objective of this current study
      was to evaluate alexidine dihydrochloride as a novel compound lead for head and
      neck cancers. Using a tetrazolium-based assay, the dose required to reduce cell
      viability by 50% (ED50) was found to be approximately 1.8 micromol/L in FaDu
      (human hypopharyngeal squamous cancer) and approximately 2.6 micromol/L in C666-1
      (human undifferentiated nasopharyngeal cancer) cells. In contrast, the ED50
      values were much higher in untransformed cells, specifically at approximately 8.8
      micromol/L in GM05757 (primary normal human fibroblast), approximately 8.9
      micromol/L in HNEpC (primary normal human nasal epithelial), and approximately
      19.6 micromol/L in NIH/3T3 (mouse embryonic fibroblast) cells. Alexidine
      dihydrochloride did not interfere with the activities of cisplatin, 5
      fluorouracil, or radiation, and interacted in a less-than-additive manner. DNA
      content analyses and Hoechst 33342 staining revealed that this compound induced
      apoptosis. Alexidine dihydrochloride-induced mitochondrial damage was visualized
      using transmission electron microscopy. Mitochondrial membrane potential
      (DeltaPsiM) depolarization was detectable after only 3 hours of treatment, and
      was followed by cytosolic Ca2+ increase along with loss of membrane
      integrity/cell death. Caspase-2 and caspase-9 activities were detectable at 12
      hours, caspase-8 at 24 hours, and caspase-3 at 48 hours. FaDu cell clonogenic
      survival was reduced to < 5% with 1 micromol/L alexidine dihydrochloride, and,
      correspondingly, this compound decreased the in vivo tumor-forming potential of
      FaDu cells. Thus, we have identified alexidine dihydrochloride as the first
      bisbiguanide compound with anticancer specificity.

PMID- 16985058
TI  - Chronic hypoxia promotes hypoxia-inducible factor-1alpha-dependent resistance to
      etoposide and vincristine in neuroblastoma cells.
AB  - Hypoxia is widespread in solid tumors as a consequence of poorly structured tumor
      derived neovasculature. Direct measurement of low oxygen levels in a range of
      adult tumor types has correlated tumor hypoxia with advanced stage, poor response
      to chemotherapy and radiotherapy, and poor prognosis. Little is known about the
      importance of hypoxia in pediatric tumors; therefore, we evaluated the effects of
      hypoxia on the response of the neuroblastoma cell lines SH-EP1 and SH-SY5Y to the
      clinically relevant drugs, vincristine, etoposide, and cisplatin. Short periods
      of hypoxia (1% O2) of up to 16 hours had no effect on drug-induced apoptosis or
      clonogenic survival. Prolonged hypoxia of 1 to 7 days leads to reduction in
      vincristine- and etoposide-induced apoptosis in SH-SY5Y and SH-EP1 cells, and
      this was reflected in increased clonogenic survival under these conditions.
      Neither short-term nor prolonged hypoxia had any effect on the clonogenic
      response to cisplatin in SH-SY5Y cells. Hypoxia-inducible factor-1 (HIF-1) alpha
      was stabilized in these cell lines within 2 hours of hypoxia but was no longer
      detectable beyond 48 hours of hypoxia. Up-regulation of carbonic anhydrase IX
      showed HIF-1alpha to be transcriptionally active. Down-regulation of HIF-1alpha
      by short hairpin RNA interference and the small-molecule 3-(5'-hydroxymethyl-2'
      furyl)-1-benzylindazole reduced hypoxia-induced drug resistance. These results
      suggest that prolonged hypoxia leads to resistance to clinically relevant drugs
      in neuroblastoma and that therapies aimed at inhibiting HIF-1alpha function may
      be useful in overcoming drug resistance in this tumor.

PMID- 16985059
TI  - Nuclear factor-kappaB maintains TRAIL resistance in human pancreatic cancer
      cells.
AB  - Although it displays promising activity in other tumor models, the effects of
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on human
      pancreatic cancer cells have not been comprehensively explored. We report that a
      majority of human pancreatic cancer cell lines (seven of nine) underwent
      apoptosis when they were exposed to recombinant human TRAIL in vitro.
      Characterization of surface TRAIL receptors by fluorescence-activated cell
      sorting showed that TRAIL-resistant cells (Panc-1 and HS766T) expressed lower
      levels of DR4 and DR5 than did TRAIL-sensitive cells. The proteasome inhibitor
      bortezomib (PS-341, Velcade) further increased TRAIL responsiveness in the TRAIL
      sensitive cells and synergized with TRAIL to reverse resistance in Panc-1 and
      HS776T cells. The effects of bortezomib were mimicked by transfection with a
      small interfering RNA construct specific for the p65 subunit of nuclear factor
      kappaB (NF-kappaB) or exposure to a selective chemical inhibitor of IKK (PS
      1145). Silencing IkappaBalpha prevented TRAIL sensitization by PS-1145,
      confirming that IkappaBalpha mediated the effects of PS-1145. NF-kappaB
      inhibition resulted in down-regulation of BCL-XL and XIAP, and silencing either
      restored TRAIL sensitivity in TRAIL-resistant cells. Finally, therapy with TRAIL
      plus PS-1145 reversed TRAIL resistance in vivo to produce synergistic growth
      inhibition in orthotopic Panc-1 tumors. Together, our results show that NF-kappaB
      inhibits TRAIL-induced apoptosis in human pancreatic cancer cells and suggest
      that combination therapy with TRAIL and NF-kappaB inhibitors, such as bortezomib,
      PS-1145, or curcumin, should be considered as a possible treatment strategy in
      patients with pancreatic cancer.

PMID- 16985060
TI  - High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic
      hypoxia for the treatment of hepatocellular carcinoma: dual effects on cancer
      cell and angiogenesis.
AB  - The present study aimed to investigate the therapeutic efficacy of combining
      vascular endothelial growth factor (VEGF) receptor blockade using tyrosine kinase
      inhibitor PTK787 with hypoxia for the treatment of hepatocellular carcinoma
      (HCC). The in vivo effects of the treatments were determined in a rat orthotopic
      HCC model, in which hypoxia was generated by hepatic artery ligation (HAL).
      Compared with HAL alone, PTK787 combined with HAL significantly prolonged the
      animal survival, reduced the tumor size, induced more tumor tissue necrosis and
      apoptosis, and down-regulated the expression of von Willebrand factor. The
      mechanism was explored in vitro using murine HCC and endothelial cell lines,
      respectively. PTK787 combined with hypoxia decreased the expression of VEGF and
      VEGF receptors in both cell lines and suppressed the cell viability by induction
      of cell cycle arrest and promotion of apoptosis. Up-regulation of cleaved form
      caspase-9 and down-regulation of Bcl-2 and cyclin D1 were detected with the
      combined treatment. Hypoxia sensitized endothelial cells to the inhibitory effect
      of PTK787 on forming tubular-like structure. The motility of tumor cells was
      inhibited by hypoxia and the combined approach, with down-regulation of Rac1,
      Rho, and phosphorylated Akt expression. However, in the endothelial cells, the
      combined treatment inhibited the hypoxia-enhanced cell motility, with suppressed
      Rac1, Rho, and phosphorylated Akt expression. In conclusion, PTK787 combined with
      hypoxia achieved a better therapeutic efficacy than hypoxia alone through
      enhancing hypoxia-induced antitumor cell effect and preventing the activation of
      angiogenic process.

PMID- 16985061
TI  - A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth
      and metastasis in vivo.
AB  - PURPOSE: Integrins are expressed by numerous tumor types including breast cancer,
      in which they play a crucial role in tumor growth and metastasis. In this study,
      we evaluated the ability of ATN-161 (Ac-PHSCN-NH2), a 5-mer capped peptide
      derived from the synergy region of fibronectin that binds to alpha5beta1 and
      alphavbeta3 in vitro, to block breast cancer growth and metastasis. EXPERIMENTAL
      DESIGN: MDA-MB-231 human breast cancer cells were inoculated s.c. in the right
      flank, or cells transfected with green fluorescent protein (MDA-MB-231-GFP) were
      inoculated into the left ventricle of female BALB/c nu/nu mice, resulting in the
      development of skeletal metastasis. Animals were treated with vehicle alone or by
      i.v. infusion with ATN-161 (0.05-1 mg/kg thrice a week) for 10 weeks. Tumor
      volume was determined at weekly intervals and tumor metastasis was evaluated by X
      ray, microcomputed tomography, and histology. Tumors were harvested for
      histologic evaluation. RESULT: Treatment with ATN-161 caused a significant dose
      dependent decrease in tumor volume and either completely blocked or caused a
      marked decrease in the incidence and number of skeletal as well as soft tissue
      metastases. This was confirmed histologically as well as radiographically using X
      ray and microcomputed tomography. Treatment with ATN-161 resulted in a
      significant decrease in the expression of phosphorylated mitogen-activated
      protein kinase, microvessel density, and cell proliferation in tumors grown in
      vivo. CONCLUSION: These studies show that ATN-161 can block breast cancer growth
      and metastasis, and provides a rationale for the clinical development of ATN-161
      for the treatment of breast cancer.

PMID- 16985062
TI  - Intracellular inhibition of carboxylesterases by benzil: modulation of CPT-11
      cytotoxicity.
AB  - Carboxylesterases are ubiquitous proteins responsible for the detoxification of
      xenobiotics. However, these enzymes also activate prodrugs, such as the
      anticancer agents capecitabine and CPT-11. As a consequence, overexpression of
      carboxylesterases within tumor cells sensitizes these cells to CPT-11. We have
      recently identified two classes of carboxylesterase inhibitors based on either a
      benzil (diphenylethane-1,2-dione) or a benzene sulfonamide scaffold and showed
      that these compounds inhibit carboxylesterases with Kis in the low nanomolar
      range. Because both classes of inhibitors show reversible enzyme inhibition,
      conventional in vitro biochemical assays would not accurately reflect the in situ
      levels of carboxylesterase activity or inhibition. Therefore, we have developed a
      novel assay for the determination of intracellular carboxylesterase activity
      using 4-methylumbelliferone as a substrate. These studies show that benzil and a
      dimethylbenzil analogue efficiently enter cells and inhibit human intestinal
      carboxylesterase and rabbit liver carboxylesterase intracellularly. This
      inhibition results in reduced cytotoxicity to CPT-11 due to the lack of
      carboxylesterase-mediated conversion of the prodrug to SN-38. These results
      suggest that intracellular modulation of carboxylesterase activity with benzil or
      its analogues may be applied to minimize the toxicity of normal cells to CPT-11.

PMID- 16985063
TI  - Adenovirus-mediated small interfering RNA against matrix metalloproteinase-2
      suppresses tumor growth and lung metastasis in mice.
AB  - Matrix metalloproteinases (MMP) are a group of proteinases that have normal
      physiologic roles degrading and remodeling the extracellular matrix. They also
      have multiple roles in different stages of tumor progression. Elevated levels of
      MMPs have been observed in many tumors; these increases have a strong association
      with the invasive phenotype. MMP-2 and MMP-9 are particularly involved in cancer
      invasion and metastasis. MMP inhibitors are currently being tested as therapeutic
      agents for a number of cancers in both preclinical models and in clinical trials.
      To date, clinical trials using this strategy have had limited efficacy. A major
      concern is the lack of specificity of commercially available MMP inhibitors. An
      adenoviral vector expressing small interfering RNA against the MMP-2 gene (Ad-MMP
      2) was constructed to specifically inhibit MMP-2 expression. The effect of Ad-MMP
      2 on invasion, angiogenesis, tumor growth, and metastasis of A549 lung cancer
      cell was evaluated. Ad-MMP-2 infection of lung cancer cells showed specific down
      regulation of MMP-2 protein, activity, and transcription as determined by Western
      blotting, gelatin zymography, and reverse transcription-PCR. Ad-MMP-2 inhibition
      also mitigated lung cancer invasion and migration, and reduced tumor cell-induced
      angiogenesis in vitro. In an experimental metastatic lung tumor model, treatment
      of established tumors by Ad-MMP-2 inhibited s.c. tumor growth and formation of
      lung nodules in mice. Adenoviral-mediated RNA interference against MMP-2 has
      significant therapeutic potential for lung cancer and exerts some of this effect
      by inhibiting angiogenesis.

PMID- 16985064
TI  - A novel plant toxin, persin, with in vivo activity in the mammary gland, induces
      Bim-dependent apoptosis in human breast cancer cells.
AB  - Phytochemicals have provided an abundant and effective source of therapeutics for
      the treatment of cancer. Here we describe the characterization of a novel plant
      toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen
      receptor-, and Bcl-2-independent mode of action. Persin was previously identified
      from avocado leaves as the toxic principle responsible for mammary gland-specific
      necrosis and apoptosis in lactating livestock. Here we used a lactating mouse
      model to confirm that persin has a similar cytotoxicity for the lactating mammary
      epithelium. Further in vitro studies in a panel of human breast cancer cell lines
      show that persin selectively induces a G2-M cell cycle arrest and caspase
      dependent apoptosis in sensitive cells. The latter is dependent on expression of
      the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is
      evidence that persin acts as a microtubule-stabilizing agent. Due to the unique
      structure of the compound, persin could represent a novel class of microtubule
      targeting agent with potential specificity for breast cancers.

PMID- 16985065
TI  - Differential efficacy of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors on
      the cell cycle of prostate cancer cells.
AB  - Members of the statin family of 3-hydroxy-3-methylglutaryl CoA reductase
      inhibitors are being investigated for the therapy and prevention of cancers
      because of their growth-inhibitory effects on epithelial cells. Some
      epidemiologic studies show that patients taking statins show a lower incidence of
      cancer compared with those taking other cholesterol-lowering medication. In
      contrast, other studies show that statin use does not correlate with cancer risk.
      To address this discrepancy, we investigated the efficacy of different statins on
      the PC-3 prostate cancer cell line and the androgen-dependent LNCaP prostate
      cancer cell line. Clinically used statins, lovastatin, fluvastatin, and
      simvastatin inhibit proliferation of the two prostate cancer cells by inducing a
      G1 arrest. Lovastatin induced the arrest at 0.5 micromol/L, a concentration
      easily reached in the serum after oral administration. Pravastatin, however, was
      less effective at inhibiting 3-hydroxy-3-methylglutaryl CoA reductase in PC-3
      cells and had to be present at 200 times higher concentrations to effect a cell
      cycle arrest. Another potential source of variability is the different levels of
      the cyclin-dependent kinase (cdk) inhibitor p27 noted in prostate cancers
      particularly because statins have been suggested to act through the induction of
      cdk inhibitors. All three statins (lovastatin, fluvastatin, and simvastatin)
      inhibited cyclin E/cdk2 kinase leading to hypophosphorylation of Rb, but this
      inhibition was correlated with a loss of the activating phosphorylation on Thr160
      of cyclin E-associated cdk2 and not dependent on the cdk inhibitors p21 and p27.
      Therefore, p27 status is unlikely to confound the epidemiologic data on the
      efficacy of statins in prostate cancer. To make definitive conclusions about the
      efficacy of statins on cancer prevention, however, the epidemiologic studies
      should take into account the type of statin used and the serum concentrations
      achieved and ensure that the tested statin inhibits the specific type of cancer
      in vitro at those concentrations.

PMID- 16985066
TI  - Real-time gene expression analysis in human xenografts for evaluation of histone
      deacetylase inhibitors.
AB  - Real-time analysis of gene expression in experimental tumor models represents a
      major tool to document disease biology and evaluate disease treatment. However,
      monitoring gene regulation in vivo still is an emerging field, and thus far it
      has not been linked to long-term tumor growth and disease outcome. In this
      report, we describe the development and validation of a fluorescence-based gene
      expression model driven by the promoter of the cyclin-dependent kinase inhibitor
      p21waf1,cip1. The latter is a key regulator of tumor cell proliferation and a
      major determinant in the response to many anticancer agents such as histone
      deacetylase inhibitors. In response to histone deacetylase inhibitors, induction
      of fluorescence in A2780 ovarian tumors could be monitored in living mice in a
      noninvasive real-time manner using whole-body imaging. Single p.o. administration
      of the histone deacetylase inhibitor MS-275 significantly induces tumor
      fluorescence in a time- and dose-dependent manner, which accurately predicted
      long-term antitumoral efficacy in individual mice following extended treatment.
      These findings illustrate that this technology allows monitoring of the
      biological response induced by treatment with histone deacetylase inhibitors. In
      addition to providing experimental pharmacokinetic/pharmacodynamic markers for
      investigational drugs, this model provides insight into the kinetics of in vivo
      regulation of transcription, which plays a key role in causing and maintaining
      the uncontrolled proliferation of tumor tissue.

PMID- 16985067
TI  - 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit ovarian cancer cell
      growth through peroxisome proliferator-activated receptor-dependent and
      independent pathways.
AB  - 1,1-Bis(3'-indolyl)-1-(p-t-butylphenyl)methane (DIM-C-pPhtBu) is a peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonist, and treatment of SKOV3
      ovarian cancer cells with this compound (5 micromol/L) inhibits cell
      proliferation, whereas up to 15 micromol/L rosiglitazone had no effect on cell
      growth. DIM-C-pPhtBu also inhibits G0-G1 to S phase cell cycle progression and
      this is linked, in part, to PPARgamma-dependent induction of the cyclin-dependent
      kinase inhibitor p21. DIM-C-pPhtBu induces PPARgamma-independent down-regulation
      of cyclin D1 and we therefore further investigated activation of receptor
      independent pathways. DIM-C-pPhtBu also induced apoptosis in SKOV3 cells and this
      was related to induction of glucose-related protein 78, which is typically up
      regulated as part of the unfolded protein response during endoplasmic reticulum
      (ER) stress. Activation of ER stress was also observed in other ovarian cancer
      cell lines treated with DIM-C-pPhtBu. In addition, DIM-C-pPhtBu induced
      CCAAT/enhancer binding protein homologous protein through both ER stress and c
      jun NH2-terminal kinase-dependent pathways, and CCAAT/enhancer binding protein
      homologous protein activated death receptor 5 and the extrinsic pathway of
      apoptosis. These results show that DIM-C-pPhtBu inhibits growth and induces
      apoptosis in ovarian cancer cells through both PPARgamma-dependent and PPARgamma
      independent pathways, and this complex mechanism of action will be advantageous
      for future clinical development of these compounds for treatment of ovarian
      cancer.

PMID- 16985068
TI  - Suppression of survivin expression in glioblastoma cells by the Ras inhibitor
      farnesylthiosalicylic acid promotes caspase-dependent apoptosis.
AB  - The Ras inhibitor farnesylthiosalicylic acid (FTS) has been shown to induce
      apoptosis in glioblastoma multiforme, but its mechanism of action was unknown. We
      show that FTS or dominant-negative Ras, by deregulating extracellular signal
      regulated kinase and Akt signaling, decreases survivin gene transcripts in U87
      glioblastoma multiforme, leading to disappearance of survivin protein and cell
      death. FTS affected both Ras-controlled regulators of survivin transcription and
      Ras-regulated survival signals. Thus, Ras inhibition by FTS resulted in release
      of the survivin "brake" on apoptosis and in activation of the mitochondrial
      apoptotic pathway: dephosphorylation of Bad, activation of Bax, release of
      cytochrome c, and caspase activation. FTS-induced apoptosis of U87 cells was
      strongly attenuated by forced expression of survivin or by caspase inhibitors.
      These results show that resistance to apoptosis in glioblastoma multiforme can be
      abolished by a single Ras inhibitor, which targets both survivin, a critical
      inhibitor of apoptosis, and the intrinsic mitochondrial apoptotic machinery.

PMID- 16985069
TI  - Microtubule-targeting agents inhibit angiogenesis at subtoxic concentrations, a
      process associated with inhibition of Rac1 and Cdc42 activity and changes in the
      endothelial cytoskeleton.
AB  - Conventional anticancer agents may display antiangiogenic effects, but the
      underlying mechanism is poorly understood. We determined the antiangiogenic
      properties of cisplatin, doxorubicin, and the microtubule-targeting agents
      docetaxel, epothilone B, and vinblastine at concentrations not affecting cell
      proliferation. We also assessed tubulin and actin morphology and the activity of
      two key molecules in cell motility, the small Rho GTPases Cdc42 and Rac1. The
      highest non-toxic concentration (HNTC) of each drug was defined as the
      concentration inhibiting a maximum of 10% human umbilical vein endothelial cell
      growth on a 1-hour drug exposure, being for cisplatin 10 micromol/L, doxorubicin
      100 nmol/L, docetaxel 10 nmol/L, epothilone B 1 nmol/L, and vinblastine 10
      nmol/L. Comparative endothelial cell functional assays using HNTCs for an
      exposure time of 1 hour indicated that endothelial cell migration in the wound
      assay, endothelial cell invasion in a transwell invasion system, and endothelial
      cell formation into tubelike structures on a layer of Matrigel were significantly
      inhibited by docetaxel, epothilone B, and vinblastine (P < 0.05), but not by
      cisplatin and doxorubicin. Docetaxel was slightly more efficient in the
      inhibition of endothelial cell motility than epothilone B and vinblastine.
      Fluorescence microscopy revealed that only the microtubule-targeting agents
      affected the integrity of the tubulin and F-actin cytoskeleton, which showed
      disturbed microtubule structures, less F-actin stress fiber formation, and
      appearance of nuclear F-actin rings. These observations were associated with
      early inhibition of Rac1 and Cdc42 activity. In conclusion, HNTCs of microtubule
      targeting agents efficiently reduce endothelial cell motility by interference
      with microtubule dynamics preventing the activation of Rac1/Cdc42 and
      disorganizing the actin cytoskeleton.

PMID- 16985070
TI  - MDM2 inhibition sensitizes neuroblastoma to chemotherapy-induced apoptotic cell
      death.
AB  - Novel therapeutic approaches are urgently needed for high-stage neuroblastoma, a
      major therapeutic challenge in pediatric oncology. The majority of neuroblastoma
      tumors are p53 wild type with intact downstream p53 signaling pathways. We
      hypothesize that stabilization of p53 would sensitize this aggressive tumor to
      genotoxic chemotherapy via inhibition of MDM2, the primary negative upstream
      regulator of p53. We used pharmacologic inhibition of the MDM2-p53 interaction
      with the small-molecule inhibitor Nutlin and studied the subsequent response to
      chemotherapy in neuroblastoma cell lines. We did 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide and terminal deoxynucleotidyl transferase assays to
      measure proliferation and apoptosis in several cell lines (IMR32, MYCN3, and JF)
      treated with combinations of cisplatin, etoposide, and Nutlin. We found
      consistent and robust decreases in proliferation and increases in apoptosis with
      the addition of Nutlin 3a to etoposide or cisplatin in all cell lines tested and
      no response to the inactive Nutlin 3b enantiomer. We also show a rapid and robust
      accumulation of p53 protein by Western blot in these cells within 1 to 2 hours of
      treatment. We conclude that MDM2 inhibition dramatically enhances the activity of
      genotoxic drugs in neuroblastoma and should be considered as an adjuvant to
      chemotherapy for this aggressive pediatric cancer and for possibly other p53 wild
      type solid tumors.

PMID- 16985071
TI  - Treatment of hormone-refractory breast cancer: apoptosis and regression of human
      tumors implanted in mice.
AB  - Following surgery, the hormone dependence of breast tumors is exploited for
      therapy using antagonists such as tamoxifen, although occasional hormone
      resistant clones do appear. Another chemotherapeutic strategy uses microtubule
      inhibitors such as taxanes. Unfortunately, these agents elicit toxicities such as
      leukocytopenia, diarrhea, alopecia, and peripheral neuropathies and are also
      associated with the emergence of drug resistance. We have previously described a
      tubulin-binding, natural compound, noscapine, that was nontoxic and triggered
      apoptosis in many cancer types albeit at 10 mumol/L or higher concentrations
      depending on the cell type. We now show that a synthetic analogue of noscapine, 9
      bromonoscapine, is approximately 10-fold to 15-fold more potent than noscapine in
      inhibiting cell proliferation and induces apoptosis following G2-M arrest in
      hormone-insensitive human breast cancers (MDA-MB-231). Furthermore, a clear loss
      of mitochondrial membrane potential, release of cytochrome c, activation of the
      terminal caspase-3, and the cleavage of its substrates such as poly(ADP-ribose)
      polymerase, suggest an intrinsic apoptotic mechanism. Taken together, these data
      point to a mitochondrially mediated apoptosis of hormone-insensitive breast
      cancer cells. Human tumor xenografts in nude mice showed significant tumor volume
      reduction and a surprising increase in longevity without signs of obvious
      toxicity. Thus, our data provide compelling evidence that 9-bromonoscapine can be
      useful for the therapy of hormone-refractory breast cancer.

PMID- 16985072
TI  - Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome
      inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2
      terminal kinase pathways.
AB  - This study was undertaken to characterize preclinical cytotoxic interactions for
      human malignancies between the multikinase inhibitor sorafenib (BAY 43-9006) and
      proteasome inhibitors bortezomib or MG132. Multiple tumor cell lines of varying
      histiotypes, including A549 (lung adenocarcinoma), 786-O (renal cell carcinoma),
      HeLa (cervical carcinoma), MDA-MB-231 (breast), K562 (chronic myelogenous
      leukemia), Jurkat (acute T-cell leukemia), MEC-2 (B-chronic lymphocytic
      leukemia), and U251 and D37 (glioma), as well as cells derived from primary human
      glioma tumors that are likely a more clinically relevant model were treated with
      sorafenib or bortezomib alone or in combination. Sorafenib and bortezomib
      synergistically induced a marked increase in mitochondrial injury and apoptosis,
      reflected by cytochrome c release, caspase-3 cleavage, and poly(ADP-ribose)
      polymerase degradation in a broad range of solid tumor and leukemia cell lines.
      These findings were accompanied by several biochemical changes, including
      decreased phosphorylation of vascular endothelial growth factor receptor-2,
      platelet-derived growth factor receptor-beta, and Akt and increased
      phosphorylation of stress-related c-Jun NH2-terminal kinase (JNK). Inhibition of
      Akt was required for synergism, as a constitutively active Akt protected cells
      against apoptosis induced by the combination. Alternatively, the JNK inhibitor
      SP600125 could also protect cells from apoptosis induced by the combination,
      indicating that both inhibition of Akt and activation of JNK were required for
      the synergism. These findings show that sorafenib interacts synergistically with
      bortezomib to induce apoptosis in a broad spectrum of neoplastic cell lines and
      show an important role for the Akt and JNK pathways in mediating synergism.
      Further clinical development of this combination seems warranted.

PMID- 16985073
TI  - Inhibition of c-Met and prevention of spontaneous metastatic spreading by the 2
      indolinone RPI-1.
AB  - Hepatocyte growth factor (HGF) and its tyrosine kinase receptor Met play a
      pivotal role in the tumor metastatic phenotype and represent attractive
      therapeutic targets. We investigated the biochemical and biological effects of
      the tyrosine kinase inhibitor RPI-1 on the human lung cancer cell lines H460 and
      N592, which express constitutively active Met. RPI-1-treated cells showed down
      regulation of Met activation and expression, inhibition of HGF/Met-dependent
      downstream signaling involving AKT, signal transducers and activators of
      transcription 3 and paxillin, as well as a reduced expression of the
      proangiogenic factors vascular endothelial growth factor and basic fibroblast
      growth factor. Cell growth in soft agar of H460 cells was strongly reduced in the
      presence of the drug. Furthermore, RPI-1 inhibited both spontaneous and HGF
      induced motility/invasiveness of both H460 and human endothelial cells. Targeting
      of Met signaling by alternative methods (Met small interfering RNA and anti
      phosphorylated Met antibody intracellular transfer) produced comparable
      biochemical and biological effects. Using the spontaneously metastasizing lung
      carcinoma xenograft H460, daily oral treatment with well-tolerated doses of RPI-1
      produced a significant reduction of spontaneous lung metastases (-75%; P < 0.001,
      compared with control mice). In addition, a significant inhibition of
      angiogenesis in primary s.c. tumors of treated mice was observed, possibly
      contributing to limit the development of metastases. The results provide
      preclinical evidence in support of Met targeting pharmacologic approach as a new
      option for the control of tumor metastatic dissemination.

PMID- 16985074
TI  - Caspase-dependent and caspase-independent apoptosis induced by evodiamine in
      human leukemic U937 cells.
AB  - Evodiamine is one of the major bioactive compounds that have been isolated and
      purified from the fruit of Evodiae fructus. Evodiamine exhibits antitumor
      activities against the human tumor cells, including multidrug-resistant tumor
      cells. However, the molecular mechanism involved in cell death induced by
      evodiamine treatment remains poorly understood. In the present study, we showed
      that evodiamine activated the caspase-dependent apoptotic pathway. This apoptosis
      was only partially inhibited by a pancaspase inhibitor benzyloxycarbonyl-Val-Ala
      Asp-fluoromethyl ketone, which suggested that evodiamine-induced apoptosis in
      leukemic U937 cells is partially caspase independent. We observed the nuclear
      translocation of apoptosis-inducing factor in evodiamine-induced apoptosis of
      U937 cells, which may be responsible for the caspase-independent apoptotic
      execution. We next showed that evodiamine induced the substantial amount of
      apoptosis both in Bcl-2- and Akt-overexpressing U937 cells but not in human
      peripheral blood mononuclear cells. Although benzyloxycarbonyl-Val-Ala-Asp
      fluoromethyl ketone inhibited caspase activity in Bcl-2-overexpressing U937
      cells, it completely prevented neither the induction of apoptosis or the nuclear
      translocation of apoptosis-inducing factor, which suggests that evodiamine is, at
      least in part, able to bypass the resistance of leukemia cells via caspase
      independent apoptotic pathways. Thus, therapeutic strategy using evodiamine may
      warrant further evaluation.

PMID- 16985075
TI  - Enhanced transduction of malignant glioma with a double targeted Ad5/3-RGD fiber
      modified adenovirus.
AB  - Malignant brain tumors remain refractory to adenovirus type 5 (Ad5)-based gene
      therapy, mostly due to the lack of the primary Ad5 receptor, the coxsackie and
      adenovirus receptor, on brain tumor cells. To bypass the dependence on coxsackie
      and adenovirus receptor for adenoviral entry and infectivity, we used a novel,
      double targeted Ad5 backbone-based vector carrying a chimeric Ad5/3 fiber with
      integrin-binding RGD motif incorporated in its Ad3 knob domain. We then tested
      the new virus in vitro and in vivo in the setting of malignant glioma. Ad5/3-RGD
      showed a 10-fold increase in gene expression in passaged cell lines and up to 75
      fold increase in primary tumors obtained from patients relative to the control.
      These results were further corroborated in our in vivo human glioma xenograft
      model, where the Ad5/3-RGD vector showed a 1,000-fold increase in infectivity as
      compared with the control. Taken together, our findings indicate that Ad5/3-RGD
      may be a superior vector for applications in glioma gene therapy and therefore
      warrants further attention in the field of neuro-oncology.

PMID- 16985077
TI  - Intracellular expression of the T-cell factor-1 RNA aptamer as an intramer.
AB  - T-cell factor (TCF)-1 protein forms the transcriptional complex with beta-catenin
      and regulates the expression of diverse target genes during early development and
      carcinogenesis. We have selected previously an RNA aptamer that binds to the DNA
      binding domain of TCF-1 and have shown that it interfered with binding of TCF-1
      to its specific DNA recognition sequences in vitro. As an approach to modulate
      the transcription by TCF/beta-catenin complex in the cells, we have developed the
      RNA expression vector for stable expression of RNA aptamer inside of the
      mammalian cells. High level of RNA was expressed as an intramer in the fusion
      with the stable RNA transcript. The RNA intramer inhibited TCF/beta-catenin
      transcription activity as shown by luciferase assay. It also modulated the
      expression of TCF/beta-catenin target genes, such as cyclin D1 and matrix
      metalloproteinase-7, as predicted to be as an effective inhibitor of the TCF
      function. In addition, it efficiently reduced the growth rate and tumorigenic
      potential of HCT116 colon cancer cells. Such RNA intramer could lead to valuable
      gene therapeutics for TCF/beta-catenin-mediated carcinogenesis.

PMID- 16985076
TI  - Targeting changes in cancer: assessing pathway stability by comparing pathway
      gene expression coherence levels in tumor and normal tissues.
AB  - The purpose of this study is to examine gene expression changes occurring in
      cancer from a pathway perspective by analyzing the level of pathway coherence in
      tumor tissues in comparison with their normal counterparts. Instability in
      pathway regulation patterns can be considered either as a result of or as a
      contributing factor to genetic instability and possibly cancer. Our analysis has
      identified pathways that show a significant change in their coherence level in
      tumor tissues, some of which are tumor type specific, indicating novel targets
      for cancer type-specific therapies. Pathways are found to have a general tendency
      to lose their gene expression coherence in tumor tissues when compared with
      normal tissues, especially for signaling pathways. The selective growth advantage
      of cancer cells over normal cells seems to originate from their preserved control
      over vital pathways to ensure survival and altered signaling, allowing excessive
      proliferation. We have additionally investigated the tissue-related instability
      of pathways, providing valuable clues to the cellular processes underlying the
      tumorigenesis and/or growth of specific cancer types. Pathways that contain known
      cancer genes (i.e., "cancer pathways") show significantly greater instability and
      are more likely to become incoherent in tumor tissues. Finally, we have proposed
      strategies to target instability (i.e., pathways that are prone to changes) by
      identifying compound groups that show selective activity against pathways with a
      detectable coherence change in cancer. These results can serve as guidelines for
      selecting novel agents that have the potential to specifically target a
      particular pathway that has relevance in cancer.

PMID- 16985078
TI  - Misclassification of gestational age in the study of spontaneous abortion.
AB  - Most studies of spontaneous abortion are subject to left truncation, because
      conception is not observed and thus pregnant women are enrolled postconception.
      Cox regression can account for left truncation but uses gestational age data,
      which may be inaccurate. Dating is affected by reporting errors and variability
      in the day of ovulation. These errors may be differential by outcome, because
      gestational ages are more likely to be clinically corrected in continuing
      pregnancies than in pregnancies ending in spontaneous abortion. Errors may be
      differential by exposure status as well, if exposures affect the time of
      ovulation. The authors designed a simulation to examine bias caused by errors in
      gestational age. Pregnancies were assigned true and alternative gestational ages
      using different assumptions about random reporting error and error due to
      variation in the time between the last menstrual period and ovulation. In
      separate scenarios, the errors were differential by outcome, differential by
      exposure, differential by both exposure and outcome, or nondifferential. Hazard
      ratios were compared using accurate versus erroneous gestational ages. For
      proportional hazards, bias was only introduced when the error in gestational age
      was differential by exposure status. Bias was greatest when the magnitude of
      error for pregnancies at higher risk was much larger than that for pregnancies at
      lower risk.

PMID- 16985079
TI  - Trans-basement membrane migration of human basophils: role of matrix
      metalloproteinase-9.
AB  - In allergic disorders, basophils migrate from the blood stream to inflamed tissue
      sites. Since trans-basement membrane migration is an important step for local
      basophil accumulation, we performed a human basophil transmigration assay using a
      model basement membrane, Matrigel. IL-3 in the upper chamber was critical for
      basophil trans-basement membrane migration over baseline levels, since none of
      the chemoattractants placed in the lower chambers induced migration. RANTES, IL
      8, 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) and platelet-activating
      factor (PAF) significantly up-regulated the transmigration of IL-3-treated
      basophils. Neutralizing experiments indicated the involvement of beta2 integrin
      and matrix metalloproteinase (MMP)-2/9 in basophil transmigration. Real-time
      quantitative PCR revealed that basophils constitutively expressed transcripts for
      MMP-9, and at lower levels, MMP-2, but cell-surface expression was only detected
      for MMP-9. MMP-9 was also detected in the cytoplasm and culture supernatant of
      the basophils. Treatment with IL-3 up-regulated the surface level of MMP-9 on the
      basophils. Our results suggest that basophils possess a unique regulatory
      mechanism for trans-basement membrane migration which is affected by cytokines,
      chemoattractants, beta2 integrin and MMPs, especially MMP-9. MMP-9 may be
      critically involved in the pathogenesis of local basophil influx in allergic
      diseases.

PMID- 16985080
TI  - Mating patterns of black oak Quercus velutina (Fagaceae) in a Missouri oak
      hickory forest.
AB  - Wind-pollinated forest trees usually have high outcrossing rates, but allogamy
      does not necessarily translate into high pollen movement. The goal of this study
      was to determine the outcrossing rates, pollen pool genetic structure, and the
      size of the effective pollination neighborhood in a population of black oak,
      Quercus velutina, in a Missouri oak-hickory forest. Based on 6 allozyme loci, 12
      maternal trees, and 439 progenies sampled along a transect of 1300 m, we found
      complete outcrossing (t(m) = 1.000, P < 0.001) and small amounts of biparental
      inbreeding. Using a TwoGener analysis of the pollen gene pool, we found
      significant structure across maternal plants (Phi(FT) = 0.078, P < 0.001), which
      when corrected for adult inbreeding translates into Phi(FT) = 0.066 that
      corresponds to an effective number of pollen donors of 7.5 individuals. Assuming
      a bivariate normal distribution and an adult density of 16.25 trees ha(-1), we
      estimated that the effective pollination neighborhood area had a radius of 41.9
      m. Even assuming that our estimates may be conservative, these findings join a
      growing body of evidence that suggest that the local neighborhood of wind
      pollinated forest tree populations may be relatively small creating opportunities
      for local selection and genetic drift.

PMID- 16985081
TI  - The mutated S1-haplotype in sour cherry has an altered S-haplotype-specific F-box
      protein gene.
AB  - Gametophytic self-incompatibility (GSI) is an outcrossing mechanism in flowering
      plants that is genetically controlled by 2 separate genes located at the highly
      polymorphic S-locus, termed S-haplotype. This study characterizes a pollen part
      mutant of the S(1)-haplotype present in sour cherry (Rosaceae, Prunus cerasus L.)
      that contributes to the loss of GSI. Inheritance of S-haplotypes from reciprocal
      interspecific crosses between the self-compatible sour cherry cultivar Ujfehertoi
      Furtos carrying the mutated S(1)-haplotype (S(1)'S(4)S(d)S(null)) and the self
      incompatible sweet cherry (Prunus avium L.) cultivars carrying the wild-type S(1)
      haplotype revealed that the mutated S(1)-haplotype confers unilateral
      incompatibility with a functional pistil component and a nonfunctional pollen
      component. The altered sour cherry S(1)-haplotype pollen part mutant, termed
      S(1)', contains a 615-bp Ds-like element within the S(1)-haplotype-specific F-box
      protein gene (SFB(1)'). This insertion generates a premature in-frame stop codon
      that would result in a putative truncated SFB(1) containing only 75 of the 375
      amino acids present in the wild-type SFB(1). S(1)' along with 2 other previously
      characterized Prunus S-haplotype mutants, S(f) and S(6m), illustrate that mobile
      element insertion is an evolutionary force contributing to the breakdown of GSI.

PMID- 16985082
TI  - A quantitative trait locus for oleic fatty acid content on Sus scrofa chromosome
      7.
AB  - A partial genome scan using microsatellite markers was conducted to detect
      quantitative trait loci (QTLs) for 10 fatty acid contents of backfat on 15
      chromosomes in a porcine resource population. Two QTLs were discovered on Sus
      scrofa chromosome 4 (SSC4) and SSC7. The QTL on SSC4 was located between marker
      loci sw1336 and sw512, and this QTL was detected (P < 0.05) only for linoleic
      acid. Its position was in proximity of those mapped for linoleic acid content in
      previous studies. The QTL on SSC7 was mapped between markers swr1343 and sw2155,
      and it was significant (P < 0.05) only for oleic acid. A novelty of the QTL for
      oleic acid was suggested because the QTL was located far from any other QTLs
      previously mapped for fatness traits. The QTL on SSC7 explained 19% of phenotypic
      variation for oleic acid content. Further studies on fine mapping and positional
      comparative candidate gene analysis would be the next step toward better
      understanding of the genetic architecture of fatty acid contents.

PMID- 16985083
TI  - Analysis of flavonoids in pubescence of soybean near-isogenic lines for
      pubescence color loci.
AB  - T and Td loci control pubescence color of soybean with epistatic effects (TT
      TdTd, tawny; TT tdtd, light tawny or near-gray; tt TdTd or tt tdtd, gray). The
      objective of this study was to investigate the nature of flavonoids in the
      pubescence of near-isogenic lines (NILs) for these loci. Flavonoids were
      extracted with methanol from pubescence of cultivar Clark with tawny pubescence
      (TT TdTd) and its NILs; from Clark-t with gray pubescence (tt TdTd) and Clark-td
      with near-gray pubescence (TT tdtd); and from a pair of NILs, To7B with tawny (TT
      TdTd) and To7G with gray pubescence (tt TdTd). Primary flavonoids were flavone
      aglycones. Luteolin and apigenin were predominant in NILs with tawny and gray
      pubescence, respectively. Small amount of 7-O-glucosides of the 2 flavones were
      also detected. Alleles at T locus were associated with 3'-hydroxylation in the B
      ring of the flavones. The primary flavonoids in Clark-td were luteolin similar to
      Clark, but its amount was halved. High performance liquid chromatography peaks
      probably corresponding to isoflavonoids were found only in Clark-td in 2003.
      However, the peaks were not observed in 2005. The above results suggest that Td
      may encode a structural or a regulatory gene controlling flavone biosynthesis.
      Pigments remained visible in pubescence after methanol extraction, suggesting
      that a major part of the pigments was polymerized. Surface rinsing experiments
      revealed that flavone aglycones exist outside the surface of cells.

PMID- 16985084
TI  - Point/counterpoint: a rebuttal to the universal Pharm.D. proposal. 1977.

PMID- 16985085
TI  - Study Commission report on pharmacy: Promised Land or Tower of Babel? 1977.

PMID- 16985086
TI  - Let us now praise famous men.... 1983.

PMID- 16985087
TI  - The human side of a pharmacy resident. 1979.

PMID- 16985088
TI  - Relationships between beliefs about medications and nonadherence to prescribed
      chronic medications.
AB  - BACKGROUND: Medication beliefs of patients with a specific medical condition have
      been associated with nonadherence to drugs used to treat that condition. However,
      associations between medication beliefs and nonadherence of individuals on
      chronic, multiple medications have not been studied. OBJECTIVE: To investigate
      associations between patients' medication beliefs and nonadherence to chronic
      drug therapy. METHODS: A cross-sectional, self-administered survey of patients
      waiting to see pharmacists at an outpatient pharmacy in a primary care clinic was
      conducted. Participants' medication beliefs were assessed using the Beliefs about
      Medicines Questionnaire, and nonadherence was assessed using the Morisky
      Medication Adherence Scale. Pearson correlation analysis was used to assess
      bivariate associations between medication beliefs and nonadherence. Regression
      was used to assess relative strength of associations between various medication
      beliefs and nonadherence and also to assess the significance of the interactions
      between those beliefs and nonadherence. RESULTS: There were positive bivariate
      associations between specific concerns about medications (p < 0.001), perceived
      general harmful effects of medications (p < 0.001), and perceived overprescribing
      of medications by physicians (p < 0.001) and medication nonadherence. When
      relative strength of associations between each medication belief and nonadherence
      was assessed, while controlling for other medication beliefs, specific-necessity
      (p = 0.02) and specific-concerns (p = 0.01) exhibited significant negative and
      positive associations with nonadherence, respectively. All two-way interactions
      between variables in the model were insignificant. A model consisting of age,
      total number of drugs used, and medication beliefs, that is, specific-necessity,
      specific-concerns, general-overuse, and general-harm, accounted for 26.5% of
      variance. Medication beliefs alone explained 22.4% of variation in nonadherence
      to chronic drug therapy. CONCLUSIONS: Patients' medication beliefs explained a
      significant portion of variation in medication nonadherence.

PMID- 16985090
TI  - Cost-effectiveness analysis of escitalopram compared with paroxetine in treatment
      of generalized anxiety disorder in the United Kingdom.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is associated with substantial
      economic burden. OBJECTIVE: To assess, from a societal perspective, the cost
      effectiveness of escitalopram and paroxetine in the treatment of GAD in the UK.
      METHOD: A decision analytic model with a 9 month time horizon was adapted to the
      UK setting. Model inputs included drug- and nondrug-specific probabilities from
      head-to-head trial data, published literature, and expert opinion. Main outcome
      measures were success (response after 12 wk of treatment and no relapse during
      the following 24 wk) and costs. Resource use was based on National Institute for
      Health and Clinical Excellence guidance for GAD patient management, and estimated
      unit costs came from standard national sources. Human capital approach was used
      to estimate costs of absence from work. The analysis was performed from the
      societal perspective. RESULTS: Escitalopram-treated patients were associated with
      14.4% higher first-line treatment success and significantly lower discontinuation
      rates due to adverse events than were those treated with paroxetine. Treatment
      with escitalopram yielded lower expected costs with greater effectiveness
      compared with paroxetine. These clinical advantages led to less sick leave and
      resource use as a result of lower switch rates and use of secondary care. Total
      expected 9 month costs were 1408 pounds sterling (2560 US dollars) lower for
      escitalopram-treated patients than for paroxetine-treated patients. Sensitivity
      analyses on key parameters demonstrated robustness of the model. CONCLUSIONS:
      Escitalopram appears to be cost-effective compared with paroxetine in the
      treatment of GAD in the UK.

PMID- 16985091
TI  - Exenatide: a new option for the treatment of type 2 diabetes.
AB  - OBJECTIVE: To evaluate available literature characterizing the pharmacology,
      pharmacokinetics, drug interactions, efficacy, and safety of exenatide in
      patients with type 2 diabetes. DATA SOURCES: A PubMed database search (1966-May
      2006) was conducted, using exenatide as the search term. The manufacturer's
      prescribing information was also used. STUDY SELECTION AND DATA EXTRACTION:
      English-language articles were selected and data were extracted with a focus on
      clinical outcomes associated with the treatment of patients with type 2 diabetes.
      DATA SYNTHESIS: Exenatide exerts a glucoregulatory effect by various mechanisms
      including secretion of glucose-dependent insulin, suppression of inappropriately
      high glucagon levels in patients with type 2 diabetes, delayed gastric emptying,
      and reduction of food intake. In placebo-controlled clinical studies, plasma
      exenatide concentrations appeared to exhibit dose-proportional kinetics, reaching
      peak plasma levels between 2 and 3 hours after a single subcutaneous injection.
      Exenatide's elimination half-life ranged from 3.3 to 4.0 hours, and the time to
      reach maximum concentration was about 2 hours. Interactions between exenatide and
      agents such as digoxin and lisinopril were not considered significant. In Phase
      III trials, exenatide demonstrated significant reduction of hemoglobin A1c levels
      from baseline and compared with placebo after 30 weeks of treatment in patients
      unable to achieve optimal glycemic control with metformin, a sulfonylurea, or
      oral combination therapy (0.4-0.9%). Patients' weight decreased with exenatide
      (0.9-2.8 kg), but adverse gastrointestinal (GI) events were common. Exenatide
      combined with thiazolidonediones, D-phenylalanine derivatives, meglitinides, or
      alpha glucosidase inhibitors has not been studied. CONCLUSIONS: Clinical trials
      have demonstrated that exenatide improves glycemic control when added to
      sulfonylureas and metformin, and it may be an alternative to insulin glargine in
      patients requiring additional therapy. Hypoglycemia has been encountered in
      clinical trials of exenatide, especially upon initiation of therapy with
      sulfonylureas (not with metformin); close patient monitoring is therefore
      recommended. Further studies should assess the impact of exenatide on clinical
      outcomes such as micro- and macrovascular disease.

PMID- 16985092
TI  - Cilomilast: orally active selective phosphodiesterase-4 inhibitor for treatment
      of chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To review available literature evaluating the pharmacology,
      pharmacokinetics, clinical efficacy, and adverse effects of cilomilast, a
      selective phosphodiesterase-4 (PDE4) inhibitor. DATA SOURCES: Literature was
      accessed through MEDLINE (1966-May 2006), Current Contents Clinical Medicine
      (1998-May 2006), and The Cochrane Library Database (1st quarter 2006) using the
      terms cilomilast, Ariflo, and SB 207 499. Reference lists from retrieved articles
      and information from the manufacturer were manually reviewed. STUDY SELECTION AND
      DATA EXTRACTION: All clinical trials evaluating cilomilast and published in
      English were included in this review. In addition, articles evaluating the
      pharmacology, pharmacokinetics, and safety of cilomilast in humans were reviewed.
      DATA SYNTHESIS: Cilomilast is a second-generation PDE4 inhibitor with
      antiinflammatory effects that target bronchoconstriction, mucus hypersecretion,
      and airway remodeling associated with chronic obstructive pulmonary disease
      (COPD). Selective PDE4 inhibition is proposed to maximize the antiinflammatory
      effects of PDE inhibition while minimizing the adverse effects of nonselective
      agents. To date, 4 clinical trials have evaluated the efficacy of cilomilast and
      demonstrated improvement in lung function (forced expiratory volume in 1 second)
      and quality of life and reduction in the occurrence of COPD exacerbations
      compared with placebo. Cilomilast is generally well tolerated, with adverse
      effects being overall mild and self-limiting. CONCLUSIONS: COPD is a progressive
      disease, and available treatment options provide limited efficacy. Given its
      unique mechanism of action and improved adverse effect profile compared with
      previous agents, cilomilast may have a promising role for the management of COPD.

PMID- 16985093
TI  - Use of non-aspirin nonsteroidal antiinflammatory drugs and the risk of
      cardiovascular events.
AB  - OBJECTIVE: To review published evidence on the use of nonselective, non-aspirin
      nonsteroidal antiinflammatory drugs (NANSAIDs) and the risks of cardiovascular
      events and examine the justification for Food and Drug Administration (FDA) in
      recommending that a cardiovascular risk warning statement be included in all
      NANSAIDs' product information inserts. DATA SOURCES: Peer-reviewed articles in
      MEDLINE (1966-August 2006) and Current Contents were identified using the key
      words NSAID, naproxen, ibuprofen, heart diseases, myocardial infarction, and
      cardiovascular events. Citations from available articles and related FDA Web
      sites were reviewed for additional references. STUDY SELECTION AND DATA
      EXTRACTION: No randomized, placebo-controlled studies have been published
      evaluating this subject. Epidemiologic evidence published in English was
      examined. Sixteen relevant studies were identified (5 cohort, 3 nested case
      control, 8 case-control). DATA SYNTHESIS: Six of the 16 studies demonstrated
      increased risk for one or more NANSAIDs (rate or ORs varied from 1.13 to 3.08).
      Five studies demonstrated cardioprotective effect for one or more NANSAIDs used
      (rate or ORs varied from 0.48 to 0.84). None of the other studies demonstrated an
      association between use of NANSAIDs and risk of cardiovascular events.
      CONCLUSIONS: After adjustment of baseline risk factors for cardiovascular events,
      epidemiologic studies demonstrated conflicting results regarding the risk of
      cardiovascular events with long-term use of nonselective NANSAIDs. However,
      considering the large number of patients consuming NANSAIDs and the potential
      public health impact, until data from long-term, randomized, controlled trials
      become available, the FDA's recommendation that a warning statement be included
      in all nonselective NANSAIDs product package inserts is justified.

PMID- 16985094
TI  - Novel therapies for Crohn's disease: focus on immunomodulators and antibiotics.
AB  - OBJECTIVE: To review the literature on novel immunomodulators such as tumor
      necrosis factor alpha (TNF-alpha)- and interleukin (IL)-related agents, 6
      thioguanine (6-TG), tacrolimus, and leflunomide, and antibiotics such as
      ornidazole, rifaximin, and ciprofloxacin for the treatment of Crohn's disease.
      DATA SOURCES: Literature was accessed through MEDLINE (1966-January 2006) using
      the terms Crohn's disease, novel therapies, immunomodulators, and antibiotics.
      Article references were hand-searched for additional relevant articles and
      abstracts. STUDY SELECTION AND DATA EXTRACTION: All articles in English
      identified from the data sources were evaluated. Studies including greater than 5
      patients with primarily adult populations were included in the review. DATA
      SYNTHESIS: There are a number of new TNF-alpha and IL-related agents that may be
      useful for management of Crohn's disease. They include CDP 571, CDP 870,
      etanercept, onercept, thalidomide, IL-10, and IL-11. Several studies have shown
      that CDP 571 decreases the Crohn's Disease Activity Index score and is promising,
      especially in patients with refractory disease. 6-TG, tacrolimus, and leflunomide
      are among other immunomodulators that appear to have a role in refractory/severe
      disease. Finally, ornidazole, rifaximin, and ciprofloxacin are antimicrobials
      that may be used in patients who have failed other therapies or as adjunctive
      therapies. CONCLUSIONS: A number of new treatment modalities are being
      investigated for Crohn's disease. Many of them are promising, and some of these
      agents may be considered in treatment-refractory patients in the future. However,
      some of the agents reviewed here are not available in the US. Future studies need
      to be double-blinded and placebo- or other treatment-controlled in a more
      homogeneous patient population.

PMID- 16985095
TI  - Cladribine: an investigational immunomodulatory agent for multiple sclerosis.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of
      cladribine, a purine analog undergoing Phase III trials for approval of its use
      in the treatment of multiple sclerosis (MS). DATA SOURCES: A MEDLINE search (1966
      September 2006) was conducted using the key words cladribine and multiple
      sclerosis. No limits were placed on the search. STUDY SELECTION AND DATA
      EXTRACTION: Studies and review articles related to cladribine and MS were
      reviewed. The trials examining the role of cladribine in MS were analyzed. DATA
      SYNTHESIS: Cladribine is a purine analog that demonstrates lymphocytotoxic
      activity. Recent data suggest that cladribine may have a role in the treatment of
      relapsing-remitting and the progressive forms of MS. In these studies, cladribine
      has shown mixed results in decreasing neurologic disability, as measured by
      various rating scales, but has consistently shown positive results in reducing
      the number of enhancing lesions, which reflects a measure of disease activity. To
      date, there is one ongoing study examining the role of oral cladribine in the
      treatment of relapsing-remitting MS. The incidence of adverse effects with
      cladribine has been significantly greater than with placebo, with the most common
      being myelosuppression. CONCLUSIONS: While data do not support its use as a first
      line MS treatment, cladribine may be a promising agent for refractory patients
      with secondary progressive MS. Further studies are warranted.

PMID- 16985096
TI  - Systematic review of medication errors in pediatric patients.
AB  - OBJECTIVE: To systematically locate and review studies that have investigated the
      incidence of medication errors (MEs) in pediatric inpatients and identify common
      errors. METHODS: A systematic search of studies related to MEs in children was
      performed using the following databases: MEDLINE (1951-April 2006), EMBASE (1966
      April 2006), Pharm-line (1978-April 2006), International Pharmaceutical Abstracts
      (1970-April 2006), Cumulative Index to Nursing and Allied Health Literature (1982
      April 2006), and British Nursing Index (1994-April 2006). Studies of the
      incidence and nature of MEs in pediatrics were included. The title, abstract, or
      full article was reviewed for relevance; any study not related to MEs in children
      was excluded. RESULTS: Three methods were used to detect MEs in the studies
      reviewed: spontaneous reporting (n = 10), medication order or chart review (n =
      14), or observation (n = 8). There was great variation in the definitions of ME
      used and the error rates reported. The most common type of ME was dosing error,
      often involving 10 times the actual dose required. Antibiotics and sedatives were
      the most common classes of drugs associated with MEs; these are probably among
      the most common drugs prescribed. CONCLUSIONS: Interpretation of the literature
      was hindered by variation in definitions employed by different researchers,
      varying research methods and setting, and a lack of theory-based research.
      Overall, it would appear that our initial concern about MEs in pediatrics has
      been validated; however, we do not know the actual size of the problem. Further
      work to determine the incidence and causes of MEs in pediatrics is urgently
      needed, as well as evaluation of the best interventions to reduce them.

PMID- 16985097
TI  - Role of the pharmacist in the community: from corner drug store to corner
      pharmacy in 40 years with friends like Harvey.

PMID- 16985098
TI  - Sulfinpyrazone C-glucuronidation is catalyzed selectively by human UDP
      glucuronosyltransferase 1A9.
AB  - The uricosuric agent sulfinpyrazone (SFZ) is metabolized via C-glucuronidation,
      an uncommon metabolic pathway, in humans. The present study aimed to characterize
      SFZ glucuronidation by human liver microsomes (HLMs) and identify the hepatic
      forms of UDP-glucuronosyltransferase responsible for this pathway. Incubations of
      SFZ with HLMs formed a single glucuronide that was resistant to beta
      glucuronidase and acid hydrolysis, consistent with formation of a C-glucuronide.
      Mass spectral analysis confirmed the identity of the metabolite as SFZ
      glucuronide (sulfinpyrazone beta-D-glucuronide; SFZG). SFZ C-glucuronidation by
      HLMs exhibited Michaelis-Menten kinetics, with mean (+/- S.D.) Km and Vmax values
      of 51 +/- 21 microM and 2.6 +/- 0.6 pmol/min . mg, respectively. Fifteen
      recombinant human UDP-glucuronosyltransferases (UGTs), expressed in HEK293 cells,
      were screened for their capacity to catalyze SFZ C-glucuronidation. Of the
      hepatically expressed enzymes, only UGT1A9 formed SFZG. UGTs 1A7 and 1A10, which
      are expressed in the gastrointestinal tract, also metabolized SFZ, but rates of
      metabolism were low compared with UGT1A9. SFZ glucuronidation by UGT1A9 exhibited
      "weak" negative cooperative kinetics, which was modeled by the Hill equation (S50
      16 microM). The data indicate that UGT1A9 is the enzyme responsible for hepatic
      SFZ C-glucuronidation and that SFZ may be used as a substrate "probe" for UGT1A9
      activity in HLMs.

PMID- 16985099
TI  - Metabolic aromatization of N-alkyl-1,2,3,4-tetrahydroquinoline substructures to
      quinolinium by human liver microsomes and horseradish peroxidase.
AB  - Metabolic aromatization of xenobiotics is an unusual reaction with some
      documented examples. For instance, the oxidation of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine to the neurotoxic pyridinium ion metabolite 1-methyl-4
      phenylpyridinium by monoamine oxidase (MAO) B in the brain has been of interest
      to a number of investigators. It has also been reported that although the
      aromatization of N-methyl-tetrahydroisoquinoline occurs with MAO B, the
      metabolism does not proceed for its isomer, N-methyl-tetrahydroquinoline, by the
      same enzyme. The aromatization of an N-alkyl-tetrahydroquinoline substructure was
      identified during in vitro metabolite profiling of compound A, which was designed
      as a potent renin inhibitor for the treatment of hypertension. The N
      alkylquinolinium metabolite of compound A was identified by liquid chromatography
      tandem mass spectrometry of human liver microsomal incubates and proton NMR of
      the isolated metabolite. Further in vitro metabolism studies with a commercially
      available chemical (compound B), containing the same substructure, also generated
      an N-alkylquinolinium metabolite. In vitro cytochrome P450 (P450) reaction
      phenotyping of compound A revealed that the metabolism was catalyzed exclusively
      by CYP3A4. Although compound B was a substrate for several P450 isoforms, its
      quinolinium metabolite was also generated predominantly by CYP3A4. Neither
      compound A nor compound B was a substrate of MAOs. The quinolinium metabolites
      were readily produced by horseradish peroxidase, suggesting that aromatization of
      the N-alkyltetrahydroquinoline could occur via a mechanism involving single
      electron transfer from nitrogen. Although dihydro intermediates from the
      tetrahydroquinoline substrates were not observed in the formation of quinolinium
      metabolites, cyanide trapping results indicated the occurrence of iminium
      intermediates.

PMID- 16985100
TI  - Rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2: implications for
      in vitro prediction of drug interactions.
AB  - Rofecoxib was recently found to greatly increase plasma concentrations of the
      CYP1A2 substrate drug tizanidine in humans, but there are no published in vitro
      studies on the CYP1A2-inhibiting effects of rofecoxib. Our objective was to
      investigate whether rofecoxib is a direct-acting or metabolism-dependent
      inhibitor of CYP1A2 in vitro. The effect of rofecoxib on the O-deethylation of
      phenacetin (20 microM) was studied using human liver microsomes. The effect of
      preincubation time on the inhibitory potential of rofecoxib was also studied, and
      the inhibitor concentration that supports half the maximal rate of inactivation
      (KI) and the maximal rate of inactivation (kinact) were determined. Rofecoxib
      moderately inhibited phenacetin O-deethylation (IC50 23.0 microM), and a 30-min
      preincubation with microsomes and NADPH considerably increased its inhibitory
      effect (IC50 4.2 microM). Inactivation of CYP1A2 by rofecoxib required NADPH, and
      was characterized by a KI of 4.8 microM and a kinact of 0.07 min(-1).
      Glutathione, superoxide dismutase, mannitol, or dialysis could not reverse the
      inactivation of CYP1A2 caused by rofecoxib. Fluvoxamine decreased the rofecoxib
      caused inactivation of CYP1A2 in a concentration-dependent manner. In conclusion,
      rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2, a cytochrome
      P450 form contributing to rofecoxib metabolism. The results provide a mechanistic
      explanation for the interactions of rofecoxib with CYP1A2 substrates and may
      partially explain its nonlinear pharmacokinetics.

PMID- 16985101
TI  - Epirubicin glucuronidation and UGT2B7 developmental expression.
AB  - The usefulness of epirubicin in the treatment of adult and childhood malignant
      diseases is related in part to the potential reduction in cardiac toxicity
      compared with that of other anthracyclines given at equivalent doses. An
      important pathway for epirubicin detoxification is UGT2B7-dependent
      glucuronidation. This study was implemented to provide a preclinical evaluation
      of the metabolism of epirubicin with respect to age-related changes in epirubicin
      glucuronidation in pediatric liver microsomes. Rates of epirubicin
      glucuronidation and levels of UGT2B7 were determined for liver microsomes from
      four pediatric age categories (n = 32) and one adult age category (n = 8). Both
      sets of data showed an increase in UGT2B7 activity and content with increasing
      age. Epirubicin glucuronidation activity in the adult group was statistically
      higher compared with all pediatric age groups (p < or = 0.01). UGT2B7 expression
      also was statistically higher in adults compared with children below 11 years of
      age, with evidence of significant differences in protein levels among the
      pediatric age categories. A positive correlation (r = 0.68) between UGT2B7 levels
      and postnatal age was observed, suggesting a progressive increase in UGT2B7
      protein expression with increasing age. However, allometric scaling using the
      (3/4) power rule suggested no difference in activity between any of the pediatric
      age categories and the adult, although only a single neonatal sample was included
      in the analysis. In summary, these in vitro data show differences in epirubicin
      glucuronidation and UGT2B7 content within pediatric age groups and support the
      use of epirubicin in pediatric patients at least 6 months of age.

PMID- 16985102
TI  - Investigation of structure and function of a catalytically efficient variant of
      the human flavin-containing monooxygenase form 3.
AB  - To characterize the contribution of amino acid 360 to the functional activity of
      the human flavin-containing monooxygenase form 3 (FMO3) and form 1 (FMO1) in the
      oxygenation of drugs and chemicals, we expressed four FMO3 variants (i.e., Ala360
      FMO3, His360-FMO3, Gln360-FMO3, and Pro360-FMO3) and one FMO1 variant (i.e.,
      Pro360-FMO1) and compared them to wild-type enzymes (Leu360-FMO3 and His360-FMO1,
      respectively). The amino acid substitutions were introduced into wild-type FMO3
      or FMO1 cDNA by site-directed mutagenesis. The thermal stability of variants of
      Leu360 FMO3 was also studied, and the thermal stability was significantly
      different from that of wild-type FMO3. The influence of different substrates to
      modulate the catalytic activity of FMO3 variants was also examined. Selective
      functional substrate activity was determined with mercaptoimidazole,
      chlorpromazine, and 10-[(N,N-dimethylaminopentyl)-2
      (trifluoromethyl)]phenothiazine. Compared with wild-type FMO3, the Ala360-FMO3
      and His360-FMO3 variants were less catalytically efficient for mercaptoimidazole
      S-oxygenation. N-Oxygenation of chlorpromazine was significantly less
      catalytically efficient for His360-FMO3 compared with wild-type FMO3. Human
      Pro360-FMO1 was significantly more catalytically efficient at S-oxygenating
      mercaptoimidazole and chlorpromazine compared with wild-type FMO1. The data
      support the mechanism that the Pro360 loci affect thermal stability of FMO3.
      Because different amino acids at position 360 affect substrate oxygenation in a
      unique fashion compared with that of FMO3 stimulation, we conclude that the
      mechanism of stimulation of FMO3 is distinct from that of enzyme catalysis. A
      molecular model of human FMO3 was also constructed to help explain the results.
      The increase in catalytic efficiency observed for Pro360 in human FMO3 was also
      observed when the His of FMO1 was replaced by Pro at loci 360.

PMID- 16985103
TI  - Intraoperative triple antenna hepatic microwave ablation.
AB  - OBJECTIVE: Microwave ablation is emerging as a new treatment option for patients
      with unresectable hepatic malignancies. This two-center study shows the results
      of a phase 1 clinical trial of patients with known hepatic masses who underwent
      synchronous triple antenna microwave ablation before elective hepatic resection.
      SUBJECTS AND METHODS: Intraoperative microwave ablation was performed before
      hepatic resection. Hepatic lesions were targeted using real-time intraoperative
      sonography with three microwave antennas positioned in a triangular
      configuration. Microwave ablation was performed at 45 W for 10 minutes. Hepatic
      resection was then completed in the standard fashion. Gross specimens were
      sectioned and measured to determine tumor and ablation sizes. Representative
      areas were stained with H and E stain and vital histochemical nicotinamide
      adenine dinucleotide (NADH) stain. RESULTS: Ten patients with a mean age of 64
      years (range, 48-79 years) were treated. Tumor histology included colorectal
      carcinoma metastases and hepatocellular carcinoma. The mean maximal tumor
      diameter was 4.4 cm (range, 2.0-5.7 cm). The mean maximal ablation diameter was
      5.5 cm (range, 5.0-6.5 cm), while the average ablation zone volume was 50.8 cm3
      (range, 30.3-65.5 cm3). Gross and microscopic examinations of areas after
      microwave ablation showed clear coagulation necrosis, even surrounding large
      hepatic vessels (> 3 mm in diameter). A marked thermallike effect was observed
      with maximal intensity closest to the antenna sites. NADH staining confirmed the
      uniform absence of viable tumor in the ablation zone. CONCLUSION: This study
      shows the feasibility of using multiple microwave antennas simultaneously in the
      treatment of liver tumors intraoperatively. Additional percutaneous studies are
      currently under way to investigate the safety and efficacy in treating
      nonsurgical candidates.

PMID- 16985104
TI  - Imaging features of hepatocellular carcinoma after transcatheter arterial
      chemoembolization and radiofrequency ablation.
AB  - OBJECTIVE: The purpose of this pictorial essay is to show the imaging features of
      hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization
      (TACE) and radiofrequency thermal ablation on CT, MRI, and contrast-enhanced
      sonography and to describe the advantages and limitations of each imaging
      technique in evaluating the therapeutic effect on HCC. CONCLUSION: CT is the
      standard imaging technique for monitoring the effectiveness of TACE and
      radiofrequency ablation. Contrast-enhanced sonography and MRI can complement CT
      in evaluating the therapeutic response.

PMID- 16985105
TI  - Diagnosis and characterization of fetal sacrococcygeal teratoma with prenatal
      MRI.
AB  - OBJECTIVE: The purpose of this study was to determine whether prenatal MRI
      provides additional information about fetal sacrococcygeal teratoma compared with
      prenatal sonography. MATERIALS AND METHODS: Twenty-two pregnant women with fetal
      sacrococcygeal teratoma underwent prenatal MRI (mean gestational age, 23 weeks).
      The size, location, mass characteristics, and compressive effects of the tumors
      were determined and correlated with sonography and postnatal findings. RESULTS:
      Based on the MRI findings, the following American Academy of Pediatrics, Surgical
      Section classifications were assigned: type I in six patients, type II in 12, and
      type III in four. No type IV tumors were found. The sacrococcygeal teratoma
      appeared entirely cystic in five fetuses, microcystic in one, mixed cystic and
      solid in 12, and solid in four. The diagnosis of sacrococcygeal teratoma was
      accurate in all cases assessed at our center using both MRI and sonography. Two
      additional patients initially referred with the diagnosis of sacrococcygeal
      teratoma had a different diagnosis at reevaluation at our institution (healthy, n
      = 1; myelomeningocele, n = 1). MRI was superior to sonography for detecting
      displacement of the colon (n = 11), urinary tract dilatation (n = 9), hip
      dislocation (n = 4), intraspinal extension (n = 2), and vaginal dilation (n = 1).
      In fetuses with sacrococcygeal teratoma types II and III, MRI better showed the
      cephalic extent of the tumor compared with sonography. MRI findings were
      confirmed at surgery or autopsy in all patients. Three fetuses with high output
      cardiac physiology underwent open fetal resection of the tumor at 21-, 24-, and
      26-weeks' gestational age with two surviving. CONCLUSION: Our results show that
      ultrafast fetal MRI is a useful adjunct to the prenatal evaluation of fetal
      sacrococcygeal teratoma. Compared with sonography, MRI more accurately
      characterized the intrapelvic and abdominal extent of the tumors and provided
      more information on compression of adjacent organs. The additional anatomic
      resolution provided by MRI resulted in more accurate prenatal counseling and
      improved preoperative planning for surgical resection.

PMID- 16985106
TI  - Radiologic findings that mimic malignancy.
AB  - OBJECTIVE: The purpose of this pictorial essay is to describe selected variant
      anatomy, benign pathology, and posttreatment appearances that may be incorrectly
      attributed to malignancy at cancer investigation. CONCLUSION: Radiologists
      involved in cancer staging should be aware of benign imaging appearances that
      simulate malignancy. Failure to correctly identify these findings as such may
      lead to unnecessary patient anxiety, incorrect tumor staging, and inappropriate
      treatment.

PMID- 16985107
TI  - MRI of adenocarcinoma of the pancreas.
AB  - OBJECTIVE: CT is the established imaging technique for evaluation of pancreatic
      adenocarcinoma. MRI, however, can play a major role in this disease. The
      objective of this study is to illustrate the strengths of MRI for evaluating
      pancreatic adenocarcinoma. CONCLUSION: The superior soft-tissue contrast of MRI
      compared with CT is useful in the detection and characterization of non-contour
      deforming pancreatic masses. MRI compared with CT may be more sensitive in the
      detection of distant disease, better for defining appropriate surgical
      candidates, and better for characterizing small liver metastases and peritoneal
      and omental metastases.

PMID- 16985108
TI  - Hydro-MRI of the small bowel: effect of contrast volume, timing of contrast
      administration, and data acquisition on bowel distention.
AB  - OBJECTIVE: The purpose of this study was to assess oral contrast agents, volumes
      of the agents, and time points of data acquisition in regard to small-bowel
      distention and patient acceptance. SUBJECTS AND METHODS: Six healthy volunteers
      underwent imaging on 16 different days. Four volumes (450, 900, 1,350, and 1,800
      mL) of each of the four contrast compounds (0.2% locust bean gum plus 2.5%
      mannitol, VoLumen containing 2.0% sorbitol, VoLumen containing 1.4% sorbitol, and
      tap water) were used. Two-dimensional true fast imaging with steady-state free
      precession data sets were acquired at 5-minute intervals after contrast
      ingestion. Distention values for small-bowel segments (duodenum, proximal and
      distal jejunum, ileum) and occurrence of side effects were documented. RESULTS:
      Analysis of bowel distention revealed significantly greater distention for all
      carbohydrate sugar alcohol-containing solutions compared with water but no
      significant difference among the three contrast agents. Sufficient duodenal
      distention was achieved with 900 mL of any of the contrast agents, but imaging
      had to be performed soon after ingestion. For MRI of the distal jejunum and
      ileum, a volume of 1,350 mL is preferable, and the time point of data acquisition
      plays a minor role. Ingestion of 1,800 mL of the carbohydrate sugar alcohol
      solutions led to a significantly higher rate of side effects such as abdominal
      cramps than did ingestion of smaller volumes. CONCLUSION: The data indicate that
      sufficient contrast consumption and optimal timing of data acquisition are
      essential to distention of the small bowel. Oral contrast agent protocols should
      be adapted to the bowel region in question.

PMID- 16985109
TI  - MRI of complicated pouchitis.
AB  - OBJECTIVE: The purpose of this study is to assess the ability of MRI to identify
      the presence of inflammation related to the pouch reservoir in symptomatic
      patients with an ileal pouch-anal anastomosis who present with clinically
      suspected complicated pouchitis. CONCLUSION: Initial results suggest that MRI
      should be considered in patients who have undergone ileal pouch-anal anastomosis
      and present a clinical impression of complicated pouchitis. MRI showed
      abnormalities consistent with complicated pouchitis in seven of nine
      examinations, with findings including pouch wall thickening, abnormal wall
      enhancement, peripouch fluid collection, sinus and fistula tract formation,
      lymphadenopathy, and peripouch stranding and fatty proliferation. MRI findings of
      complicated pouchitis should raise the suspicion of Crohn's disease and should
      prompt further investigation.

PMID- 16985110
TI  - CT findings in duodenal diverticulitis.
AB  - OBJECTIVE: Duodenal diverticulitis is a rare complication of duodenal
      diverticulosis. It is often clinically misdiagnosed because it has no
      pathognomonic signs or symptoms and its CT findings may mimic other
      intraabdominal processes. We describe two patients with duodenal diverticulitis
      who presented with abdominal pain, nausea, and leukocytosis. At the time of
      initial presentation, only one of the two patients was diagnosed correctly. In
      the first case, which was initially misdiagnosed as acute pancreatitis, the
      correct diagnosis was evident only after the disease process had become more
      quiescent and a follow-up CT scan using orally and i.v.-administered contrast
      agents was performed. In the second case, the coronal reformatted images
      confirmed the diagnosis suggested by the axial images. CONCLUSION: Duodenal
      diverticulitis can be a difficult CT diagnosis to make; however, maintaining it
      in the differential diagnosis of duodenal and pancreatic inflammatory processes
      and masses as well as defining the anatomy with nonaxial imaging including
      coronal images may be helpful in confirming the diagnosis.

PMID- 16985111
TI  - Radiologic findings of gastrointestinal complications in an adult patient with
      Henoch-Schonlein purpura.

PMID- 16985112
TI  - Liver involvement in hereditary hemorrhagic telangiectasia: CT and clinical
      findings do not correlate in symptomatic patients.
AB  - OBJECTIVE: The purpose of our study was to report the multiphasic CT findings in
      patients with symptomatic liver involvement by hereditary hemorrhagic
      telangiectasia (HHT) and to correlate the CT findings with the type of clinical
      presentation. CONCLUSION: Patients with symptomatic HHT liver disease have
      diffuse hepatic telangiectases, a dilated common hepatic artery, and a high
      incidence of biliary abnormalities. Multiphasic CT is useful in diagnosing liver
      involvement due to HHT; however, no strong correlation was seen between CT
      findings and the clinical subtype of HHT liver disease.

PMID- 16985113
TI  - Hepatic hemangiomas with arterioportal shunt: sonographic appearances with CT and
      MRI correlation.
AB  - OBJECTIVE: The purpose of this study was to summarize and illustrate the
      sonographic appearance of hepatic hemangiomas with arterioportal shunt and to
      correlate them with CT and MRI findings. CONCLUSION: High-flow hepatic
      hemangiomas tend to be seen as hypoechoic lesions at sonography. In the presence
      of fatty infiltration in the liver, they may accompany peritumoral low-echoic
      areas presumably caused by peritumoral sparing of fatty infiltration similar to a
      hyperattenuating or hyperintense peritumoral rim on unenhanced CT or MR chemical
      shift imaging. Color Doppler sonography may reveal intratumoral flows, large
      feeding arteries, and reversal of portal flow around the tumor. Knowledge of such
      sonographic findings may ensure an accurate sonographic diagnosis of these
      tumors.

PMID- 16985114
TI  - MRI of primary prostatic Wilms' tumor in a young adult.

PMID- 16985115
TI  - Giant myoepithelioma of the face: MDCT with 2D and 3D images.

PMID- 16985116
TI  - Transcutaneous contrast-enhanced sonography of peripheral lung lesions.
AB  - OBJECTIVE: Transpulmonary sonography contrast agents, in conjunction with
      contrast-specific imaging techniques, are increasingly accepted in clinical use
      for diagnostic imaging of several organs. Anatomically, the lung is characterized
      by dual blood sources, supplied from both the pulmonary and bronchial arteries.
      Contrast-enhanced sonography enables us to determine whether the pulmonary or the
      bronchial arteries are the source of blood to lung lesions, depending on the time
      to enhancement and the extent of enhancement after contrast agent application.
      CONCLUSION: This article reports our first experience with transcutaneous
      contrast-enhanced sonography for the diagnosis and differential diagnosis of
      peripheral lung lesions.

PMID- 16985118
TI  - Ureteral fibroepithelial polyp on MDCT urography.

PMID- 16985117
TI  - Higher intracoronary attenuation improves diagnostic accuracy in MDCT coronary
      angiography.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the amount of
      intracoronary attenuation influences the diagnostic accuracy of MDCT coronary
      angiography in the detection of clinically significant stenosis. MATERIALS AND
      METHODS: One hundred twenty patients in sinus rhythm with suspected coronary
      artery disease who underwent MDCT of the heart and conventional coronary
      angiography were retrospectively selected. The population was divided into two
      groups depending on median (326 H) coronary vascular enhancement (i.e., low
      attenuation and high attenuation). The diagnostic accuracy of MDCT for the
      detection of clinically significant coronary artery lesions (> or = 50% lumen
      reduction) in both groups was compared with that of quantitative coronary
      angiography. RESULTS: The sensitivity of MDCT was 90% and 93% for the low- and
      high-attenuation groups, respectively. The specificity was 95% and 97%.
      CONCLUSION: Greater intracoronary attenuation leads to higher diagnostic accuracy
      in the detection of coronary artery stenosis with MDCT.

PMID- 16985119
TI  - Gel-gel double-lumen silicone breast implant: mimic of intracapsular implant
      rupture.

PMID- 16985120
TI  - An extreme case of retrorenal colon.

PMID- 16985121
TI  - Contrast agent for intrathecal gadolinium administration.

PMID- 16985122
TI  - Concurrent routine breast and thyroid sonography for detection of thyroid tumors.

PMID- 16985123
TI  - How to win the coronary CTA turf war.

PMID- 16985124
TI  - Commentary on "Arthrotomography of the temporomandibular joint".

PMID- 16985125
TI  - Nonradiologist utilization of American College of Radiology Appropriateness
      Criteria in a preauthorization center for MRI requests: applicability and
      effects.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects and
      applicability of use of the American College of Radiology (ACR) Appropriateness
      Criteria by nonradiologist physicians in an MRI preauthorization center.
      MATERIALS AND METHODS: All MRI requests received at our preauthorization center
      during a 19-month period were included in the study. The study period was divided
      into preintervention and postintervention phases, indicating before and after
      introduction of the ACR criteria to the general practitioners staffing our
      center. ACR appropriateness values were classified into three groups:
      appropriate, indeterminate, and inappropriate. Requests for which a matching ACR
      value could not be assigned were labeled ACR-noncodable. Multiple parameters
      evaluated and compared for the two phases included rate of request receipt, total
      approval and denial rates, and approval and denial rates according to the ACR
      Appropriateness Criteria and by anatomic region to be evaluated. RESULTS: There
      was no significant change in rate of request receipt and total approval and
      denial rates. However, there was an increase in the rate of approval of
      appropriate requests (phase 1, 71/96 [74%]; phase 2, 74/76 [97%]; p < 0.001) and
      the rate of denial of inappropriate requests (phase 1, 0/12 [0%]; phase 2, 9/13
      [69%]; p < 0.001). More than 40% of requests were marked "ACR-noncodable" because
      of a lack of a matching clinical condition or variant. CONCLUSION: Introduction
      of the ACR Appropriateness Criteria resulted in an increase in the rate of
      performance of appropriate MRI examinations and a decrease in the rate of
      performance of inappropriate MRI examinations. ACR Appropriateness Criteria were
      applicable to approximately 50% of MRI requests.

PMID- 16985126
TI  - Chance-type fractures of the thoracolumbar spine: imaging analysis in 53
      patients.
AB  - OBJECTIVE: Chance-type fractures are subtle unstable injuries that are often
      associated with intraabdominal injuries. CT-based observations made during
      routine interpretations revealed involvement of a burst component to this
      fracture pattern and a clue on the transaxial images to its presence. The purpose
      of this review was to determine how often these features occurred in a
      retrospective study of a large sample because these findings influence diagnosis
      and management. MATERIALS AND METHODS: A retrospective review of all patients
      identified from the University of Maryland Shock Trauma Center trauma registry
      and IDXRad system diagnosed with flexion-distraction injuries of the
      thoracolumbar spine over an 8-year period was performed. Three trauma
      radiologists assessed the admission spinal radiographs, CT studies with
      multiplanar images, and available MRI examinations. Imaging findings were
      confirmed by consensus. Abdominopelvic CT studies and surgical reports were
      reviewed for evidence and type of intraabdominal injury. A literature review of
      previous similar series was performed. RESULTS: Fifty-three patients were
      identified for inclusion in the study. Associated intraabdominal injury occurred
      in 40% and most commonly involved the bowel and mesentery. A close examination of
      the fracture patterns on CT revealed that a burst-type fracture with posterior
      cortex buckling or retropulsion was a common finding (48%). Also, serial
      transaxial CT images often (76%) showed a gradual loss of definition of the
      pedicles that we refer to as the "dissolving pedicle" sign. The study showed that
      the horizontally oriented fracture planes through the posterior elements can
      often be recognized radiographically, but these fractures can be very subtle.
      CONCLUSION: Intraabdominal injuries occurred in 40% of flexion-distraction
      thoracolumbar fractures in our study cohort, which is slightly lower than
      previously reported. About half of the patients with this injury displayed a
      burst-type component that could have a significant influence on surgical
      management. The dissolving pedicle sign can assist in recognition of this often
      subtle injury on transaxial CT.

PMID- 16985127
TI  - Response of nonmidline pain to percutaneous vertebroplasty.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of
      nonmidline symptoms in patients undergoing percutaneous vertebroplasty and the
      response of these symptoms to vertebroplasty. MATERIALS AND METHODS: This is a
      retrospective study performed through examination of patient records, baseline
      questionnaires, demographic sheets, follow-up questionnaires, reports from
      telephone follow-up, and pain location diagrams completed before and after
      percutaneous vertebroplasty. Data were gathered from 350 patient encounters, 686
      vertebroplasty procedures, and 288 patients. After determining the prevalence of
      nonmidline pain, analysis of acquired data was performed to determine the
      efficacy of vertebroplasty in relieving nonmidline pain. RESULTS: Nonmidline pain
      was present in 240 of 350 patient encounters. Major symptom areas were the ribs;
      hip, groin, and buttocks; and legs and thighs. Lesser areas of nonmidline
      symptoms were the abdomen, shoulders, and waistline. Overall there was
      improvement in nonmidline pain in 83% of the procedures. CONCLUSION: Most
      patients presenting for percutaneous vertebroplasty have nonmidline pain.
      Vertebroplasty reduced or eliminated nonmidline pain in 76-92% of the patients in
      whom it was reported. Procedures involving lumbar vertebrae tended to be
      successful less often than others, but even in these patients the procedure was
      successful in approximately 75%.

PMID- 16985128
TI  - Epidemiologic, clinical, and imaging findings in brucellosis patients with
      osteoarticular involvement.
AB  - OBJECTIVE: The aim of this study was to assess the epidemiologic and clinical
      features, complications, imaging findings, and outcomes for brucellosis patients
      with osteoarticular involvement. SUBJECTS AND METHODS: This prospective study was
      performed over 4 years (December 2000-December 2004). The subjects were 251
      Turkish patients (age range, 2-77 years) who were diagnosed with brucellosis
      during that period. Joint sonography, radiography, radionuclide bone
      scintigraphy, and MRI were performed in all patients with osteoarticular and
      spinal manifestations. RESULTS: The disease was acute in 92 patients (36.7%),
      subacute in 48 patients (19.1%), and chronic in 111 patients (44.2%). Sonography
      of the joints showed bursitis in 13 patients (5.2%). Radiography, MRI, and
      scintigraphy revealed 71 patients (28.3%) with sacroiliitis, 26 (10.4%) with
      spondylodiskitis, three (1.2%) with acute osteomyelitis, and one (0.4%) with
      avascular necrosis of the femoral head. All patients received combinations of
      either two or three antibiotics. Surgery was performed in three patients with
      spinal instability or radiculopathy. CONCLUSION: Brucellosis is endemic to some
      regions. MRI is the method of choice for diagnosing osteoarticular and spinal
      complications of human brucellosis, especially during the early phase. It is
      important to differentiate tuberculous spondylodiskitis from brucellar
      spondylodiskitis because proper treatment for each of these diseases can prevent
      complications. The radiologic findings for these two forms of spondylodiskitis
      are similar, so serologic testing for brucellosis is necessary in such cases.

PMID- 16985129
TI  - 3.0-T MRI of the supraspinatus tendon.
AB  - OBJECTIVE: MRI of the shoulder has been found to be highly sensitive and specific
      for detection of full-thickness supraspinatus tendon tears at 1.5-T or lower
      field strength compared with arthroscopy. MRI of the shoulder at 3.0 T has not
      been specifically assessed. This study assesses the sensitivity and specificity
      of MRI at 3.0 T for supraspinatus tendon tears compared with arthroscopy.
      MATERIALS AND METHODS: Two experienced musculoskeletal radiologists
      retrospectively reviewed MR images of the shoulder in 150 consecutive patients
      who had subsequent arthroscopy. All patients had oblique coronal and sagittal T1
      weighted and fat-saturated T2-weighted axial, oblique coronal, and sagittal
      imaging performed. The radiologists interpreted the MR images by consensus
      without knowledge of the arthroscopy results. Scans were interpreted for full
      thickness or partial-thickness supraspinatus tendon tears. If partial-thickness
      supraspinatus tendon tears were seen on MRI, the reviewers noted whether the
      partial-thickness tear was articular or bursal in location. The radiologists also
      separated the supraspinatus tendon tears into small (< 1 cm retraction from the
      humeral head) and large (> 1 cm retraction from the humeral head). All 150
      patients went on to arthroscopy. After consensus review of the MR images,
      arthroscopy results were compared with consensus MR interpretations. RESULTS:
      Ninety-eight of the 150 patients had full-thickness supraspinatus tendon tears at
      arthroscopy. Twenty-six of the 150 patients had partial-thickness supraspinatus
      tendon tears. Seventeen of these 26 partial-thickness tears were along the
      articular surface and nine were along the bursal surface. Ninety-six of 98 full
      thickness tears seen at arthroscopy were seen on consensus MRI interpretation.
      All 26 partial-thickness tears seen at arthroscopy were seen at consensus MR
      interpretation; however, two of the partial-thickness articular surface tears
      seen at arthroscopy were interpreted as full-thickness tears on consensus MRI
      interpretation. Twenty-eight of the 98 full-thickness supraspinatus tendon tears
      were small tears (< 1 cm retraction from the humeral head) on arthroscopy. Two of
      these 28 small tears seen on arthroscopy were not seen on consensus MRI
      interpretation. Twenty-six patients had intact supraspinatus tendons on both
      retrospective consensus MRI interpretation and at arthroscopy. CONCLUSION: MRI of
      the shoulder at 3.0 T is highly sensitive and specific compared with arthroscopy
      in the detection of full-thickness and partial-thickness supraspinatus tendon
      tears.

PMID- 16985130
TI  - MR arthrography in the differential diagnosis of type II superior labral
      anteroposterior lesion and sublabral recess.
AB  - OBJECTIVE: The objective of our study was to assess the utility of five MR
      arthrographic findings in differentiating type II superior labral anteroposterior
      (SLAP) lesion from superior sublabral recess. MATERIALS AND METHODS: The MR
      arthrograms of 55 patients (57 cases) with either type II SLAP lesion (34 cases)
      or superior sublabral recess (23 cases) who underwent arthroscopic surgery and MR
      arthrography were retrospectively reviewed. Two independent reviewers searched
      for the extension, direction, and shape of high signal intensity in the superior
      labrum on MR arthrograms. In addition, the presence of concomitant anterosuperior
      labral tear and anteroposterior extension of high signal intensity on axial
      images was evaluated. The frequencies of these findings in cases of type II SLAP
      lesion and sublabral recess were evaluated, and the statistical significance of
      each finding in differentiation of the two groups was assessed. RESULTS:
      Extension of high signal intensity behind the biceps anchor that extended beneath
      the labrum on fat-saturated oblique coronal T1-weighted images was found in 33
      (97%) of the cases of type II SLAP lesion and 21 (91%) of the cases of sublabral
      recess. Laterally curved high signal intensity was found in 17 (50%) of the cases
      of type II SLAP lesion but in only four (17%) of the cases of sublabral recess.
      Globular or irregular shape of the superior labrum was present in 22 (65%) of the
      cases of type II SLAP lesion and in 10 (43%) of the cases of sublabral recess.
      Concomitant anterosuperior labral tear was seen in 14 (41%) of the cases of type
      II SLAP lesion but in only two (8.7%) of the cases of sublabral recess.
      Anteroposterior extension of high signal intensity in the superior labrum on fat
      saturated axial T1-weighted images was detected in 33 cases of type II SLAP
      lesion (97%) and in 14 cases of sublabral recess (61%). CONCLUSION: Although the
      MR arthrographic findings were similar for type II SLAP lesion and sublabral
      recess, laterally curved high signal intensity on oblique coronal images,
      concomitant anterosuperior labral tear, and anteroposterior extension of high
      signal intensity on axial images were helpful findings in the diagnosis of type
      II SLAP lesion.

PMID- 16985131
TI  - Involvement of the anterior portion of the subacromial-subdeltoid bursa in the
      painful shoulder.
AB  - OBJECTIVE: The purpose of our study was to verify that increased widening of the
      anterior portion of the subacromial-subdeltoid bursa is associated with
      anteromedial shoulder pain. MATERIALS AND METHODS: Bursography, sonography, and
      CT were performed in six cadaver shoulders and compared with anatomic sections in
      neutral position and while the humerus was extended and internally rotated. For
      the clinical study, the width of the anterior portion of the bursa was measured
      in both positions in both shoulders of 27 patients referred because of shoulder
      pain and in eight asymptomatic volunteers. Pain was coded as absent, experienced
      in the anteromedial portion of the shoulder, or experienced elsewhere but not
      anteromedially, and we compared the pain scores between shoulder positions.
      RESULTS: In all cadaver shoulders, when compared with CT scans and anatomic
      sections, sonography showed the morphology of the bursa, its relationships with
      surrounding structures, and morphologic changes associated with position. In
      volunteers, the mean width of the bursa was 0.74 +/- 0.05 and 0.93 +/- 0.09 mm (p
      = 0.013), respectively, in neutral and stress position. In patients, the same
      values were 0.70 +/- 0.07 and 0.81 +/- 0.14 mm (p = 0.286) in the asymptomatic
      side and 1.20 +/- 0.11 and 1.75 +/- 0.23 mm (p < 0.001) in the symptomatic side,
      respectively. The bursa was wider in patients experiencing pain anteromedially
      than in those who experienced pain elsewhere and volunteers (p = 0.002 and <
      0.001, respectively), and the bursa was wider in symptomatic shoulders than in
      asymptomatic shoulders (p < 0.001). CONCLUSION: Widening of the anterior portion
      of the subacromial-subdeltoid bursa is associated with anteromedial shoulder pain
      and the clinical syndrome of coracoid impingement.

PMID- 16985132
TI  - MRI of stress reaction of the distal humerus in elite tennis players.
AB  - OBJECTIVE: The purpose of this study was to describe the MRI appearance of stress
      reaction in the distal humerus in 12 elite tennis players. In addition, we aimed
      to determine whether any MRI findings were associated with changes in recovery
      times. CONCLUSION: Stress injury to the distal humerus is a cause of chronic arm
      pain among elite tennis players and may be exacerbated during full competition.
      The degree of marrow edema on STIR MRI may be predictive of time to return to
      competition.

PMID- 16985133
TI  - MR angiography of the hand with subsystolic cuff-compression optimization of
      injection parameters.
AB  - OBJECTIVE: The purpose of our study was to assess the impact of various injection
      rates on contrast-enhanced high-resolution 3D MR angiography of the hand.
      MATERIALS AND METHODS: Ten healthy individuals (mean age, 24.4 years; range, 20
      27 years) underwent 3D contrast-enhanced MR angiography of both hands. Starting 3
      minutes before data acquisition, subsystolic upper arm cuff compression was
      applied unilaterally. A 1.5-T whole-body scanner with 3D gradient-echo sequence
      was used. Seven data sets (20 seconds) were obtained consecutively. I.v. contrast
      material of 0.1 mg/kg of body weight of gadobutrol was injected at rates of 0.5,
      1.0, and 1.5 mL/s. For both hands, quantitative data evaluation was performed
      with contrast-to-noise ratio (CNR) in the radial, ulnar, palmar, and digital
      arteries and veins. Qualitative assessment of the arterial visualization score
      and venous contamination score was rated by two experienced radiologists using a
      4-point scale. RESULTS: The lowest venous contamination score (CNR and reviewers'
      assessment) was observed with an injection rate of 0.5 mL/s (p < 0.05). For the
      arterial signal, the reviewers' assessment was that an injection rate of 0.5 mL/s
      was best (p = 0.08). Compression yielded a significantly lower venous
      contamination score for the compressed side than for the noncompressed side for
      flow rates of 0.5 mL/s and 1.0 mL/s (p < 0.05). CONCLUSION: Image quality of hand
      MR angiography was better with cuff compression. A flow rate of 0.5 mL/s yielded
      a good CNR and a significantly lower venous contamination score than the other
      flow rates.

PMID- 16985134
TI  - Use of the "two-slice-touch" rule for the MRI diagnosis of meniscal tears.
AB  - OBJECTIVE: We reviewed our experience with knee MRI to determine if using the
      "two-slice-touch" rule increased our positive predictive value for diagnosing
      meniscal tears. This rule classifies a meniscus as torn if there are two or more
      MR images with abnormal findings and as possibly torn if there is only one MR
      image with an abnormal finding. We also compared our sensitivity and specificity
      using fast spin-echo imaging with previously reported studies. MATERIALS AND
      METHODS: We reviewed the medical records of 174 patients who had knee MR
      examinations and correlative knee arthroscopy to determine our accuracy when we
      diagnosed menisci as torn, possibly torn, or intact using knee arthroscopy as the
      gold standard. RESULTS: Our positive predictive value increased from 91% to 94%
      (p = 0.37) for medial meniscal tears and from 83% to 96% (p = 0.02) for lateral
      meniscal tears when using the two-slice-touch rule compared with the standard
      criterion of diagnosing a meniscus as torn if one or more images are abnormal.
      When using the standard criterion, we had 95% sensitivity and 85% specificity for
      diagnosing medial meniscal tears and 77% sensitivity and 89% specificity for
      diagnosing lateral meniscal tears. CONCLUSION: When using the two-slice-touch
      rule, we had an increased positive predictive value for diagnosing menisci as
      torn, which was statistically significant for the lateral meniscus. Our accuracy
      using the standard criterion with fast spin-echo imaging was comparable to that
      reported in previous studies with spin-echo imaging.

PMID- 16985135
TI  - Classification of common acetabular fractures: radiographic and CT appearances.
AB  - OBJECTIVE: Accurate characterization of acetabular fractures can be difficult
      because of the complex acetabular anatomy and the many fracture patterns. In this
      article, the five most common acetabular fractures are reviewed: both-column, T
      shaped, transverse, transverse with posterior wall, and isolated posterior wall.
      Fracture patterns on radiography are correlated with CT, including multiplanar
      reconstruction and 3D surface rendering. CONCLUSION: In the evaluation of the
      five most common acetabular fractures, assessment of the obturator ring, followed
      by the iliopectineal and ilioischial lines and iliac wing, for fracture allows
      accurate classification. CT is helpful in understanding the various fracture
      patterns.

PMID- 16985136
TI  - CT-guided transthoracic needle biopsy using a puncture site-down positioning
      technique.
AB  - OBJECTIVE: We have developed a new CT-guided technique using puncture site-down
      positioning during the biopsy. The goal of our study was to determine the
      efficacy and safety of this technique for biopsy of lung lesions compared with
      the standard technique. MATERIALS AND METHODS: Medical records of 236 patients
      who underwent CT-guided transthoracic needle biopsy were retrospectively
      evaluated. This study included 89 cases that were biopsied using the standard
      technique (group A) and 147 cases that were biopsied using the puncture site-down
      positioning technique (group B). A 20-gauge automated cutting needle without
      coaxial technique was used in all patients. Medical records were reviewed for
      lesion size and location, biopsy results, and complications. RESULTS: When using
      the standard technique, the sensitivity for malignant lesions was 96.1%; the
      sensitivity for benign lesions, 92.1%; and diagnostic accuracy, 94.4%. Thirty
      seven patients (41.6%) had pneumothorax, with 16 (18.0%) requiring chest tube
      placement. When using the puncture site-down positioning technique, the
      sensitivity for malignant lesions was 95.4%; the sensitivity for benign lesions,
      93.3%; and diagnostic accuracy, 94.6%. Nineteen patients (12.9%) had
      pneumothorax, with four (2.7%) requiring chest tube placement. Other
      complications were minimal. CONCLUSION: CT-guided transthoracic needle biopsy
      using the puncture site-down positioning technique is an effective and safe
      procedure with a high diagnostic accuracy and low complication rate. This new
      technique is especially useful in reducing the rate of pneumothorax.

PMID- 16985137
TI  - Transbronchial biopsy guided by low-dose MDCT: a new approach for assessment of
      solitary pulmonary nodules.
AB  - OBJECTIVE: The objective of our study was to determine whether transbronchial
      bronchoscopic biopsy of solitary pulmonary nodules under CT guidance using a low
      dose protocol can increase diagnostic yield in patients who had undergone
      unsuccessful conventional bronchoscopic biopsy. SUBJECTS AND METHODS: We included
      33 consecutive patients (25 men; mean age +/- SD, 64 +/- 9.6 years) with solitary
      pulmonary nodules at different sites and with a lesion-to-pleura distance of at
      least 2 cm who previously underwent conventional bronchoscopy that did not result
      in histologic diagnosis. All patients were prospectively investigated with
      transbronchial bronchoscopic biopsy under MDCT guidance. Examinations were
      performed with the patient in conscious sedation using a low-dose protocol (80
      kV, 20 mAs, 5-mm collimation, 10-mm slices). The position of the tip of the
      biopsy device was confirmed and documented before biopsies were performed. All
      specimens were examined by standard histopathologic techniques. The effective
      radiation dose was calculated for every patient. RESULTS: The diagnostic yield
      was 24 in 33 selected patients (overall accuracy, 72.7%): 13 (54%) had primary
      lung cancer and 11 (46%) had benign diagnoses. The formal operative
      characteristics were sensitivity, 59%; specificity, 100%; positive predictive
      value, 100%; and negative predictive value, 55%. The final diagnoses of the
      remaining nine patients in whom transbronchial bronchoscopic biopsy was not
      diagnostic were non-small cell lung cancer (n = 3); small cell lung cancer (n =
      3); and alveolar carcinoma, carcinoid tumor, and hemorrhaged bulla (n = 1 each).
      All nonmalignant diagnoses were confirmed by 6 months radiographic and clinical
      follow-up. The mean duration of the procedure was 39 +/- 15 minutes, and the
      average effective dose was 0.7 mSv (range, 0.5-1.1 mSv). One case of pulmonary
      hemorrhage (3%) occurred after the procedure. CONCLUSION: MDCT-guided
      transbronchial bronchoscopic biopsy is a promising and safe tool for the
      diagnostic pathway of solitary pulmonary nodules in previously undiagnosed
      patients. Image quality was sufficient with low-dose protocols, which resulted in
      low radiation exposure for patients and personnel.

PMID- 16985138
TI  - Single-session prolonged alcohol-retention sclerotherapy for large hepatic cysts.
AB  - OBJECTIVE: Our purpose was to evaluate the safety and therapeutic efficacy of
      single-session prolonged alcohol sclerotherapy in treating large hepatic cysts. A
      therapeutic comparison between 4-hour and 2-hour retention techniques was also
      studied. MATERIALS AND METHODS: Twenty-seven patients with 31 hepatic cysts were
      enrolled in this study. Seventeen patients (18 cysts) were treated by alcohol
      retention for 4 hours (group 1) and 10 patients (13 cysts) for 2 hours (group 2).
      The mean diameter of the hepatic cysts was 12.4 cm (range, 8-23 cm) with a
      comparable size range in each group. The sclerosing agent used was 95% alcohol,
      and the maximum amount was limited to 200 mL. Patients changed position and vital
      signs were monitored every 10-15 minutes. The blood alcohol concentrations were
      checked hourly for 5 consecutive hours in the initial nine patients. The
      nonparametric Mann-Whitney U test was used to compare the difference in
      characteristics and treatment results of the subjects between these two groups.
      The level of statistical significance was set at a p value of less than 0.05.
      RESULTS: All but one patient in group 2 tolerated the entire course of
      sclerotherapy. The mean aspirated volume and mean injected alcohol volume of the
      hepatic cysts were 730 mL and 138.3 mL, respectively, in group 1 patients, and
      931 mL and 139 mL, respectively, in group 2 patients. The mean maximum blood
      alcohol concentration was 128.2 mg/dL (range, 60-199 mg/dL) at 3-4 hours after
      alcohol instillation. The mean posttherapy residual cystic diameter was 2.5 cm
      (range, 0-6 cm), with an average volume reduction rate of 98.3% and 97.7%,
      respectively, for patients in group 1 and group 2 after a mean follow-up period
      of 29.6 months (9-59 months). No statistical differences of the mean reduction
      rate between the two groups were noted. CONCLUSION: Long retention of the alcohol
      in a single-injection technique is safe and effective. Two-hour alcohol retention
      has a comparable efficacy to that of 4-hour retention.

PMID- 16985139
TI  - Breast cancer awareness: taking charge of women's health.

PMID- 16985140
TI  - The valuable role of the women's imaging section in AJR: breast imaging.

PMID- 16985141
TI  - Lobular neoplasia at 11-gauge vacuum-assisted stereotactic biopsy: correlation
      with surgical excisional biopsy and mammographic follow-up.
AB  - OBJECTIVE: The objective of our study was to evaluate the outcome of lobular
      neoplasia diagnosed at 11-gauge stereotactic vacuum-assisted biopsy (SVAB).
      MATERIALS AND METHODS: Retrospective review of 1,819 lesions sampled with 11
      gauge SVAB yielded 27 patients with lobular neoplasia as the most severe
      pathologic entity diagnosed. Patients with lobular neoplasia associated with
      atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or
      infiltrating carcinoma were excluded. Twenty patients underwent surgical
      excisional biopsy, and seven patients were followed mammographically for a mean
      of 52 months (range, 14-67 months). Mammographic lesion type, number of specimens
      obtained per lesion, and specific histologic features related to lobular
      carcinoma in situ (LCIS) were assessed. Results were compared with histologic
      findings at surgery or mammographic follow-up. RESULTS: Nineteen lesions
      presented mammographically as microcalcifications, four as masses, three as
      masses with associated microcalcifications, and one as architectural distortion.
      A mean of 13 specimens were obtained per lesion. Carcinoma was found at surgical
      excision in 19% of the lesions (5/27). Lesions were upgraded to DCIS (n = 2),
      invasive lobular carcinoma (n = 2), and mixed invasive ductal and lobular
      carcinoma (n = 1). In addition to the diagnosis of lobular neoplasia at SVAB, one
      patient presented with synchronous infiltrating ductal carcinoma in the
      contralateral breast, and two patients developed metachronous infiltrating ductal
      carcinoma in a different quadrant of the ipsilateral breast. Twelve of the 27
      lesions included LCIS. These lesions were evaluated pathologically to distinguish
      the classic (10/12) from the pleomorphic (2/12) form of this entity. Ten of the
      12 LCIS cases underwent surgical excisional biopsy with four of the five upgrades
      occurring in these patients. Only one of these patients was shown to have the
      pleomorphic type of LCIS. Lesions in seven patients who underwent mammographic
      follow-up remained stable. CONCLUSION: The known association of lobular neoplasia
      with high-risk and malignant lesions at surgical biopsy requires careful
      consideration when lobular neoplasia is diagnosed as the most severe histologic
      entity at SVAB. The diagnosis of lobular neoplasia at 11-gauge SVAB is not
      reliable in view of the 19% upgrade rate at the time of surgical excisional
      biopsy in our study. No predictive mammographic features allowed distinction
      between the patients with lesions that were upgraded at the time of surgery from
      those whose lesions were not upgraded.

PMID- 16985142
TI  - Hysterosalpingography for assessing efficacy of Essure microinsert permanent
      birth control device.
AB  - OBJECTIVE: The Essure microinsert is a new U.S. Food and Drug Administration
      approved method of birth control. The objective of this study is to report our
      initial experience using hysterosalpingography (HSG) to assess its efficacy for
      permanent tubal occlusion. CONCLUSION: The Essure microinsert produced tubal
      blockage in all patients. As this device may become more widely used,
      radiologists should be aware of the device's appearance and be able to assess
      device position and presence of tubal occlusion on HSG.

PMID- 16985143
TI  - Sonography, CT, and MRI appearance of the Essure microinsert permanent birth
      control device.
AB  - OBJECTIVE: The purpose of this article is to describe the appearance and location
      of the Essure permanent birth control device on sonography, CT, and MRI.
      CONCLUSION: The Essure device has a distinct appearance and typical location that
      allow it to be accurately identified on sonography, CT, and MRI scans.

PMID- 16985144
TI  - Inversion mode display of 3D sonography: applications in obstetric and
      gynecologic imaging.
AB  - OBJECTIVE: Three-dimensional sonography involves volume acquisitions of
      sonographic data that can be displayed in a variety of ways, including surface
      rendering and multiplanar reconstruction. A new method of displaying sonographic
      volumes is called the inversion mode, which displays the cystic portions within
      the entire volume as echogenic areas. The gray-scale portion of the image becomes
      transparent, and the cystic areas become brightly visible in three dimensions.
      CONCLUSION: This article shows the applications for this method of volume
      sonography display and shows the importance of being able to visualize all of the
      cystic areas concurrently within a volume.

PMID- 16985145
TI  - Low-cost phantom for stereotactic breast biopsy training.
AB  - OBJECTIVE: This article reports on the construction of a low-cost phantom to be
      used for training technologists, residents, and radiologists to perform
      stereotactic breast biopsy. The model is adaptable to a variety of biopsy devices
      and realistically simulates the aspects of stereotactic breast biopsy.
      CONCLUSION: We believe our model provides an excellent alternative to more
      expensive commercial products.

PMID- 16985146
TI  - Angiographic diagnosis of inflammatory bowel disease in patients presenting with
      gastrointestinal bleeding.
AB  - OBJECTIVE: The objective of our study was to review the final diagnosis and
      outcome in patients undergoing visceral angiography for gastrointestinal
      hemorrhage in whom a diagnosis of inflammatory bowel disease (IBD) had been
      suspected on the basis of angiographic findings. MATERIALS AND METHODS: A
      retrospective review was performed of all visceral angiography referrals over a
      10-year period. During that time, 522 visceral angiograms were obtained for the
      investigation of acute or chronic gastrointestinal bleeding. IBD was reported as
      a possible or probable diagnosis based on the angiographic findings in 43
      patients (8.2%) (male-to-female ratio, 23:20; age range, 11-79 years; mean age,
      48.6 years). RESULTS: Active IBD was confirmed in 25 (58%) of these 43
      individuals (male-to-female ratio, 15:10; mean age, 46.5 years), representing
      4.8% of all patients referred for the investigation of gastrointestinal bleeding.
      In 14 of these individuals, a diagnosis of IBD had not been suspected previously.
      A diagnosis other than IBD was found to be the cause of the angiographic findings
      in seven subjects. In the 32 patients in whom a cause for the angiographic
      findings was identified, IBD was the diagnosis in 25 (78%). CONCLUSION: In a
      group of patients referred for angiography to investigate acute or chronic
      gastrointestinal bleeding, IBD can be expected to be the cause in approximately
      5%. Radiologists should be aware of the angiographic abnormalities seen in
      patients with IBD and be prepared to consider this diagnosis even if the results
      of other previous investigations have been reported as normal.

PMID- 16985147
TI  - Localization of appendix with MDCT and influence of findings on choice of
      appendectomy incision.
AB  - OBJECTIVE: The purpose of this study was to show the relation between McBurney's
      point and the appendix in patients undergoing 3D MDCT and to investigate the
      effect of this information on a surgeon's choice of appendectomy incision.
      MATERIAL AND METHODS: Among 142 adults undergoing consecutive MDCT studies, 100
      patients (35 women, 65 men; mean age, 52.1 years) with an identifiable appendix
      on abdominopelvic MDCT examinations were selected for the study group. The
      presence of intraabdominal mass or a history of abdominal surgery were the
      exclusion criteria. Three-dimensional reconstruction of the CT data was performed
      with a surface shaded display algorithm. The locations of the base of the
      appendix and McBurney's point were marked on a single 3D image that allowed
      display of the skin surface markings for each patient. The superoinferior and
      mediolateral distances from the level of the appendix to the level of McBurney's
      point were measured, and the radial distance was calculated from these
      measurements. A surgeon experienced in emergency abdominal surgery reviewed 3D CT
      images and one axial image showing the appendix, and his choice of incision for
      each patient based on the CT information was recorded. The influence of the
      superoinferior and mediolateral distances of the appendix from McBurney's point
      on the surgeon's decision was analyzed with a multivariate logistic regression
      model. RESULTS: The appendix was exactly at McBurney's point in only 4% of the
      patients. In 36% of the cases, the appendix was within 3 cm, in 28% of cases it
      was 3-5 cm, and in 36% of the cases it was more than 5 cm away from McBurney's
      point. Mean +/- SD superoinferior, mediolateral, and radial distances between the
      appendix and McBurney's point were 33.0 +/- 24.1, 20.8 +/- 19.3, and 42.1 +/-
      26.7 mm, respectively. After reviewing the images, the surgeon would have altered
      his incision site in 35% of the cases. The surgeon preferred a higher incision in
      28% and a lower incision in 7% of the cases. Both positive and negative
      superoinferior displacement away from McBurney's point were significant factors
      regarding the surgeon's decision to alter the incision (p = 0.005), and the
      superoinferior distance was more than 3 cm in 94% of the cases in which the
      surgeon would have altered the incision. CONCLUSION: The location of the appendix
      varies widely among individuals, and McBurney's point has limitations as an
      anatomic landmark. Three-dimensional MDCT findings can be useful to surgeons
      customizing appendectomy incisions. Additional information about the location of
      the appendix in the CT report (if possible, together with a 3D image showing the
      location of the appendix) may be beneficial for surgeons performing appendectomy.

PMID- 16985148
TI  - MRI in evaluating atrophy of the external anal sphincter in patients with fecal
      incontinence.
AB  - OBJECTIVE: External anal sphincter atrophy seen at endoanal MRI may predict poor
      outcome of surgical anal sphincter repair for an external anal sphincter defect.
      The purposes of this study were to compare external phased-array MRI to endoanal
      MRI for depicting external anal sphincter atrophy in patients with fecal
      incontinence and to evaluate observer reproducibility in detecting external anal
      sphincter atrophy with these techniques. SUBJECTS AND METHODS: Thirty patients
      with fecal incontinence (23 women, seven men; mean age, 58.7 years; age range, 37
      78 years) underwent both endoanal and external phased-array MRI. Images were
      evaluated for external anal sphincter atrophy by three radiologists. Measures of
      differences and agreement between both MRI techniques and of interobserver and
      intraobserver agreement of both techniques were calculated. RESULTS: The MRI
      techniques did not significantly differ in their ability to depict external anal
      sphincter atrophy (p = 0.63) with good agreement (kappa = 0.72). Interobserver
      agreement was moderate (kappa = 0.53-0.56) for endoanal MRI and moderate to good
      (kappa = 0.55-0.8) for external phased-array MRI. Intraobserver agreement was
      moderate to very good (kappa = 0.57-0.86) for endoanal MRI and fair to very good
      (kappa = 0.31-0.86) for external phased-array MRI. CONCLUSION: External phased
      array MRI is comparable to endoanal MRI in depicting external anal sphincter
      atrophy and, thereby, in selecting patients for anal sphincter repair. Because
      results among interpreters varied considerably depending on the experience level,
      both techniques can be recommended in the diagnostic workup of fecal incontinence
      only if sufficient experience is available.

PMID- 16985149
TI  - Accessory left gastric artery from left hepatic artery shown on MDCT and
      conventional angiography: correlation with CT hepatic arteriography.
AB  - OBJECTIVE: The objective of our study was to evaluate the diagnostic accuracy of
      MDCT and conventional angiography in the detection of an accessory left gastric
      artery using CT hepatic arteriography as the standard of reference. MATERIALS AND
      METHODS: The study group consisted of 118 patients who underwent MDCT with a
      triple-phase liver protocol with a slice thickness of 5 mm, conventional
      angiography, and CT hepatic arteriography. The early-phase images of MDCT and
      conventional angiography were retrospectively reviewed. The presence or absence
      of an accessory left gastric artery was evaluated using CT hepatic arteriography
      as the standard of reference. The sensitivity, specificity, and accuracy of MDCT
      and conventional angiography were calculated. RESULTS: CT hepatic arteriography
      revealed an accessory left gastric artery in 25 (21.2%) of 118 cases, including
      15 proximal- and 10 distal-type accessory left gastric arteries. On MDCT, there
      were seven false-negative cases and one false-positive case. Six of the seven
      false-negative cases were a proximal-type accessory left gastric artery, and nine
      of 10 distal-type accessory left gastric arteries were correctly diagnosed using
      MDCT. The sensitivity, specificity, and accuracy of MDCT were 72.0%, 98.9%, and
      93.2%, respectively. On conventional angiography, there were three false-negative
      and two false-positive cases, none of whom underwent selective left hepatic
      arteriography. Two of the three false-negative cases were the distal-type
      accessory left gastric artery, but eight of the 10 distal-type accessory left
      gastric arteries were correctly diagnosed. The sensitivity, specificity, and
      accuracy of conventional angiography were 88.0%, 97.8%, and 95.8%, respectively.
      CONCLUSION: Approximately 70% of accessory left gastric arteries can be diagnosed
      at the early phase of MDCT even with a slice thickness of 5 mm.

PMID- 16985150
TI  - High-resolution CT of the chest in children and young adults who were born
      prematurely: findings in a population-based study.
AB  - OBJECTIVE: The purpose of this study was to use a scoring system for high
      resolution CT in the evaluation of radiologic findings in young people born
      extremely preterm and to examine the reproducibility of this scoring system.
      SUBJECTS AND METHODS: High-resolution CT of the lungs was assessed in 72 children
      born at a gestational age of < or = 28 weeks or with a birth weight of < or =
      1,000 g within a defined region in western Norway in 1982-1985 (n = 40) or in
      1991-1992 (n = 32). All images were analyzed by two pediatric radiologists using
      a scoring system in which a total of 14 features were assessed. RESULTS: Sixty
      three (88%) of the subjects had abnormal findings, the most common being linear
      opacities (n = 52), triangular opacities (n = 42), air trapping (n = 19), and
      mosaic perfusion (n = 10). Right and left lungs were equally affected. There were
      fewer abnormalities in the younger age group (born in 1991-1992). Intraobserver
      agreement and interobserver agreement were moderate (weighted kappa = 0.54 and
      kappa = 0.52, respectively). Fifty-six of the 72 children had a clinical
      diagnosis of bronchopulmonary dysplasia, and the median total score and the
      median scores of the four most common findings were higher in the
      bronchopulmonary dysplasia group; however, the differences were not statistically
      significant. CONCLUSION: High-resolution CT in young people of preterm birth
      revealed abnormal radiologic findings in 81.3% of the patients at age 10 years
      and 92.5% at age 18 years. Linear, triangular, and subpleural opacities were the
      most common. The reproducibility of the applied scoring system was acceptable.

PMID- 16985151
TI  - Detection of air trapping on inspiratory and expiratory phase images obtained by
      0.3-second cine CT in the lungs of free-breathing young children.
AB  - OBJECTIVE: The objective of our study was to evaluate whether 0.3-second cine CT
      can be used to detect air trapping in the lungs of young children. SUBJECTS AND
      METHODS: In 30 children (mean age, 25 months), 0.3-second cine CT was performed
      at six levels during 3 seconds of quiet breathing. The study population was
      divided into an air trapping group (n = 24) and a no-air trapping group (n = 6).
      Lung density was measured at an abnormal area (with or without air trapping) and
      an adjacent normal area on inspiratory and expiratory phase images. Lung density
      differences between inspiration and expiration were calculated and compared in
      abnormal areas (with or without air trapping) and in normal areas. Their
      percentages were calculated and compared between the two groups. In addition,
      lung density differences between abnormal and adjacent normal areas were
      calculated and compared between the two groups. RESULTS: Lung density differences
      between inspiration and expiration were smaller in areas with air trapping (mean
      +/- SD, -19 +/- 34 H) than in abnormal areas without air trapping (138 +/- 36 H)
      (p < 0.001) or in normal areas (111 +/- 49 H) (p < 0.001). Their percentages were
      smaller in the group with air trapping (-27% +/- 54%) than in the group with no
      air trapping (120% +/- 87%) (p < 0.001). In the group with air trapping, lung
      density differences were larger at the expiratory phase (260 +/- 77 H) than at
      the inspiratory phase (129 +/- 69 H) (p < 0.001), but did not change through the
      respiratory cycle in the group with no air trapping (p > 0.05). CONCLUSION: Air
      trapping can be accurately detected in the lungs of free-breathing young children
      using 0.3-second cine CT.

PMID- 16985152
TI  - Pulmonary tuberculosis in infants: radiographic and CT findings.
AB  - OBJECTIVE: As complications of tuberculosis are frequent in infancy, correct
      diagnosis of tuberculosis in infants is important. The purposes of this study are
      to summarize radiographic and CT findings of pulmonary tuberculosis in infants
      and to determine the radiologic features frequently seen in infants with this
      disease. CONCLUSION: Frequent radiologic findings of pulmonary tuberculosis in
      infants are mediastinal or hilar lymphadenopathy with central necrosis and air
      space consolidations, especially masslike consolidations with low-attenuation
      areas or cavities within the consolidation. Disseminated pulmonary nodules and
      airway complications are also frequently detected in this age group. CT is a
      useful diagnostic technique in infants with tuberculosis because it can show
      parenchymal lesions and tuberculous lymphadenopathy better than chest
      radiography. CT scans can also be helpful when chest radiographs are inconclusive
      or complications of tuberculosis are suspected.

PMID- 16985153
TI  - Combining MDCT, micturating cystography, and excretory urography for 3D imaging
      of cloacal malformation.

PMID- 16985154
TI  - Correlation of relative permeability and relative cerebral blood volume in high
      grade cerebral neoplasms.
AB  - OBJECTIVE: The purpose of this study was to correlate the degree of contrast
      enhancement on dynamic contrast-enhanced T1-weighted MRI and the relative
      cerebral blood volume (rCBV) values on T2*-weighted MRI in patients with high
      grade brain neoplasms. SUBJECTS AND METHODS: Ten patients with biopsy-proven high
      grade gliomas underwent dynamic contrast-enhanced MRI using T1-weighted fast
      spoiled gradient-echo technique (TR/TE, 8.3/1.5) during i.v. infusion of 0.1
      mmol/kg of MR contrast medium. This sequence was followed within 5 minutes by
      dynamic susceptibility contrast (DSC) imaging (1,500/80) during i.v. infusion of
      0.2 mmol/kg of MR contrast medium. Dynamic contrast-enhanced analysis was
      performed using the maximum-signal-intensity algorithm, and DSC analysis was
      performed using the negative enhancement integral program. For each tumor, we
      performed two comparisons: first, the average dynamic contrast-enhanced and rCBV
      values within a region of interest drawn around the entire contrast-enhancing
      tumor on a single image through the center of the lesion and, second, the highest
      dynamic contrast-enhanced and highest rCBV values within each tumor. Statistical
      analyses of the first comparison were performed using Pearson's correlation
      coefficient, R2 correlation coefficient, and Spearman's rank correlation and for
      the second comparison using Kendall's tau correlation. RESULTS: The mean signal
      intensity values ranged between 3.48 and 7.16 SDs above baseline values (mean,
      4.89 SDs). The mean rCBV values ranged between 57.9% and 122.7% of the normal
      lentiform nucleus (mean, 76.6%). The Pearson's correlation coefficient was 0.867,
      the R2 correlation coefficient was 0.752, and the Spearman's rank correlation was
      0.794 (p = 0.001). Dynamic contrast-enhanced values from the region of highest
      signal intensity ranged between 7.7 and 48.6 SDs above baseline values (mean,
      17.3 SDs). The highest rCBV values ranged between 105% and 400% of the normal
      lentiform nucleus (mean, 292%). The correlation was estimated to be 0.7778 and
      was statistically significant at the 0.01 level of statistical significance (p =
      0.0035). CONCLUSION: We found a high correlation between degree of contrast
      enhancement on dynamic contrast-enhanced images and rCBV values in whole tumors
      and in regions having the highest degree of contrast enhancement in this small
      study. Our findings, which suggest that relative permeability and rCBV values may
      be correlated in high-grade glial neoplasms, deserve further study in a larger
      patient population.

PMID- 16985155
TI  - Findings on brain MRI from research studies of occupational exposure to known
      neurotoxicants.
AB  - OBJECTIVE: The expanding use of MRI in large-scale epidemiologic studies of CNS
      outcomes has led to increasing concern for the consistent handling of incidental
      findings. Our purpose is to identify the prevalence of incidental neuroradiologic
      abnormalities in an adult population with past occupational exposure to lead who
      underwent brain MRI as part of a large, longitudinal cohort study. MATERIALS AND
      METHODS: Structural MR images obtained for the research study were reviewed by a
      neuroradiologist on an ongoing basis for findings of clinical concern. The
      subjects were recruited as part of a longitudinal research study designed to
      examine the effects of past lead exposure on CNS structures. The cohort examined
      consisted of 589 men who previously worked at an organolead manufacturing
      facility and had a wide range of lead exposure durations and intensities. MR
      images were also reviewed from 67 population-based control subjects from the same
      study who had no history of occupational lead exposure. RESULTS: Incidental
      findings were detected in 84% (548/656) of research subjects. Of the 548 subjects
      with abnormalities, 30% (167) required no referral, 51% (280) required routine
      referral, 17% (93) required urgent referral, and 1.5% (8) required immediate
      referral. Incidental findings of all categories were observed in a larger
      percentage of older subjects, aged 60 years and above. Using multivariable
      logistic regression analysis, we found that age (p < 0.0001), but not lead
      history, was associated with an increased risk of incidental neuroradiologic
      abnormalities. CONCLUSION: In the population examined, there was a high
      prevalence of incidental brain and head and neck abnormality. Of particular
      concern were the serious health problems observed requiring urgent or immediate
      referral in 18.5% of the subjects. These findings underscore the need for
      radiologists to evaluate the anatomic images generated by research studies,
      particularly those with an older population base.

PMID- 16985156
TI  - Comparison of MRI sequences to detect ventriculitis.
AB  - OBJECTIVE: The ability of different MRI sequences to depict characteristic
      findings suggestive of ventriculitis was compared. CONCLUSION: The study
      comprised 20 brain MRI studies in 13 patients who had a final diagnosis of
      ventriculitis. Both diffusion-weighted imaging and FLAIR imaging were equally and
      highly sensitive for detecting intraventricular debris and pus--the most common
      MRI finding suggestive of ventriculitis. FLAIR imaging was superior to contrast
      enhanced T1-weighted imaging for depicting ventricular wall abnormalities--a less
      common finding that also is suggestive of ventriculitis.

PMID- 16985157
TI  - MDCT angiography of the spinal vasculature and the artery of Adamkiewicz.
AB  - OBJECTIVE: The purpose of our study was to prospectively assess 40-MDCT
      technology in combination with adapted brain reconstruction algorithms to
      visualize the spinal vasculature, in particular the artery of Adamkiewicz and its
      anatomic variants. SUBJECTS AND METHODS: One hundred patients underwent contrast
      enhanced MDCT of the thoracolumbar junction with collimation of 40 x 0.625 mm.
      The adapted brain algorithm reconstructed the spinal canal with a field of view
      of 90 mm at 0.6-mm slice thickness. Curved multiplanar reformations identified
      the artery of Adamkiewicz as a continuous vascular tract extending from the
      aortic orifices of the intercostal or lumbar arteries via the anterior
      radiculomedullary artery to the anterior spinal artery. Segment of origin and
      length were noted. Diameter and contrast-to-noise ratio (CNR) were evaluated
      along the posterior branch, the radiculomedullary artery, the artery of
      Adamkiewicz, and the anterior spinal artery. Univariate general linear model
      analysis with Bonferroni post hoc corrections evaluated whether laterality,
      segment of origin, and length of the artery of Adamkiewicz showed a sex-specific
      propensity. Multivariate general linear model analysis assessed whether spinal
      vascular diameters and intraluminal CNR showed correlations with sex, laterality,
      and segment of origin. Finally, the luminal diameters of the feeding posterior
      branches were statistically compared with those of the ipsilateral and
      contralateral adjacent posterior branches. RESULTS: Successful depiction of the
      artery of Adamkiewicz was achieved in all patients; longitudinally the artery
      measured 40.1 +/- 13.51 mm. In 63% of patients it originated from the left side
      of the body, and in 74% it originated from the level of the 10th-12th thoracic
      vertebrae. Duplications were found in 5% of patients. Segmental distribution,
      laterality, and length did not show significant sex-specific differences (p >
      0.05). The vascular diameter and luminal contrast did not show significant
      differences caused by sex, laterality, or segment of origin (p > 0.05). The
      diameter of the posterior branches (2.8 +/- 0.71 mm) arising in the segments of
      origin showed a significantly wider lumen than any of the other posterior
      branches (contralateral, 1.9 +/- 0.32 mm; upper ipsilateral, 2.0 +/- 0.47 mm;
      lower ipsilateral, 1.9 +/- 0.39 mm) (p < 0.0001). CONCLUSION: Contrast-enhanced
      40-MDCT technology, in combination with an adapted brain reconstruction
      algorithm, can depict the artery of Adamkiewicz and its anatomic variants.

PMID- 16985158
TI  - Sonography of the eye.
AB  - OBJECTIVE: The purpose of this study is to show how sonography can reveal
      pathology of the eye and to highlight its usefulness as a simple and cost
      effective tool in investigating eye symptoms. CONCLUSION: The cystic nature of
      the eye, its superficial location, and high-frequency transducers make it
      possible to clearly show normal anatomy and pathology such as tumors, retinal
      detachment, vitreous hemorrhage, foreign bodies, and vascular malformations.
      Sonography is useful as a treatment follow-up technique because it has no adverse
      effects. Sonography is well tolerated by patients and relatively easy to perform
      for those familiar with real-time sonography.

PMID- 16985159
TI  - MDCT angiography of the pulmonary arteries: influence of body weight, body mass
      index, and scan length on arterial enhancement at different iodine flow rates.
AB  - OBJECTIVE: The purpose of this study was to assess whether body weight, body mass
      index, and scan length influence arterial enhancement during CT angiography (CTA)
      of the pulmonary arteries at different iodine flow rates. MATERIALS AND METHODS:
      CTA examinations of the pulmonary arteries performed for routine clinical care of
      120 patients between March and December 2003 were retrospectively evaluated.
      Patients had received either 120 mL of contrast medium with an iodine
      concentration of 300 mg I/mL (group A) or 90 mL of contrast medium with an iodine
      concentration of 400 mg I/mL (group B). The iodine dose was 36 g, and the
      injection rate was 4 mL/s in all examinations. The iodine flow rate was 1.2 g I/s
      in group A and 1.6 g I/s in group B. Arterial attenuation along the z-axis was
      measured per patient, and the influence of body weight, body mass index, and scan
      length on enhancement of the pulmonary arteries in the two groups was assessed.
      RESULTS: In group A and in group B, body weight and body mass index correlated
      significantly with mean enhancement along the z-axis (r = -0.35 and -0.26 for
      group A and -0.48 and -0.40 for group B). Scan length showed no correlation with
      pulmonary attenuation. Mean pulmonary artery enhancement was significantly higher
      in group B with a difference of 51 H compared with group A. CONCLUSION: Pulmonary
      artery attenuation in CTA of the pulmonary arteries shows a small but significant
      correlation with body weight and body mass index independently of the iodine flow
      rate used. A higher iodine flow rate improves pulmonary artery enhancement.

PMID- 16985160
TI  - Quantitative assessment of lung cancer perfusion using MDCT: does measurement
      reproducibility improve with greater tumor volume coverage?
AB  - OBJECTIVE: To date, quantitative assessment of tumor vascularity using perfusion
      CT has been limited to a single tumor level, with the potential for measurement
      error in heterogeneous tumors. We aimed to determine if greater z-axis tumor
      coverage improves the reproducibility of perfusion CT measurements in lung
      cancer. SUBJECTS AND METHODS: Paired perfusion studies were performed on 10
      patients who had histologically confirmed advanced non-small cell lung cancer.
      Using 16-MDCT, multiple sequential volumetric acquisitions encompassing the
      entire tumor were acquired after infusion of i.v. contrast material. Using Patlak
      analysis, median values of tumor permeability (mL/100 mL/min) and blood volume
      (mL/100 mL) were measured for 10-mm z-axis coverage, and for 40-mm z-axis
      coverage in each of the paired perfusion studies. Measurement reproducibility was
      evaluated using Bland-Altman statistics. RESULTS: Mean difference (95% limits of
      agreement) for tumor permeability was 1.4 (-4.0 to 6.8) for 10-mm coverage and
      0.8 (-3.6 to 5.2) for 40-mm coverage. Mean difference (95% limits of agreement)
      for blood volume was 1.9 (-5.1 to 8.9) for 10-mm coverage and 1.4 (-3.7 to 6.6)
      for 40-mm coverage. The coefficient of variation for permeability was 18.7% for
      10-mm coverage, improving to 11.9% for 40-mm coverage. The coefficient of
      variation for blood volume was 41.7% for 10-mm coverage, improving to 32.6% for
      40-mm coverage. CONCLUSION: Our results show that an improvement in tumor
      perfusion measurement reproducibility may be achieved with greater z-axis
      coverage.

PMID- 16985161
TI  - Thin-section CT findings in hematopoietic stem cell transplantation recipients
      with respiratory virus pneumonia.
AB  - OBJECTIVE: The purpose of this study was to use serial thin-section CT scans to
      assess the incidence of respiratory viral infection and lung abnormalities in a
      large patient population at high risk of pulmonary complications. MATERIALS AND
      METHODS: The study population consisted of 26 recipients of hematopoietic stem
      cell transplants who had proven respiratory viral pneumonia. In all cases, thin
      section CT scans were obtained before fiberoptic bronchoscopy and bronchoalveolar
      lavage. The study included only patients in whom bronchoalveolar lavage fluid
      showed no evidence of organisms other than respiratory viruses. The CT scans were
      assessed for the presence, extent, and anatomic distribution of ground-glass
      attenuation, air-space consolidation, nodules, centrilobular branching structures
      (tree-in-bud), thickening of the bronchovascular bundles, and pleural effusion.
      RESULTS: Areas of ground-glass attenuation were identified in 24 (92%) of 26
      patients and were the only finding in eight patients. Multiple nodules, seen in
      17 (65%) of 26 patients, measured 3-10 mm in diameter or were larger than 10 mm.
      The nodules had a centrilobular or random distribution. A tree-in-bud appearance
      was seen in six of the patients with centrilobular nodules. This pattern had a
      bilateral distribution and involved mainly the lower lung zones. CT revealed
      thickening of the bronchovascular bundles in 16 (61%) of the patients. Thickening
      was bilateral in 14 and unilateral in two patients. Bronchial wall thickening
      involved the lower lobes in six patients and had a patchy random distribution in
      the remaining nine patients. Air-space consolidation was present in nine (35%) of
      the cases. It had a lobular or subsegmental distribution in eight of the patients
      and a segmental distribution in one patient. Areas of consolidation were randomly
      distributed throughout the lungs in all cases. Less common findings included
      bilateral pleural effusion and bronchial dilatation. CONCLUSION: Respiratory
      viral infection is common among adult recipients of hematopoietic stem cell
      transplants, occurring over a wide time span after transplantation. The presence
      of respiratory viral infection must be considered in any patient with new
      respiratory symptoms, fever, or findings at CT such as extensive or patchy areas
      of ground-glass opacities or a mixture of patterns, most commonly ground-glass
      attenuation, thickening of the bronchial walls, and multiple small nodules.

PMID- 16985162
TI  - Live 3D echocardiography: a replacement for traditional 2D echocardiography?
AB  - OBJECTIVE: We describe the development of real-time 3D imaging and review the
      previously used versions of 3D echocardiography so that the reader will
      appreciate why current developments truly do represent a quantum leap in the
      technology. CONCLUSION: Three-dimensional echocardiography has now been shown to
      have several advantages over 2D echocardiography, particularly for volume
      measurements, visualization of septal defects, and whole-valve evaluation. Given
      these data, it is clear that 3D echocardiography is here to stay and soon will
      become part of routine echocardiographic examinations.

PMID- 16985163
TI  - Time-resolved contrast-enhanced MR angiography of the thorax in adults with
      congenital heart disease.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic value of time
      resolved contrast-enhanced MR angiography in adults with congenital heart
      disease. SUBJECTS AND METHODS: Twenty patients with congenital heart disease
      (mean age, 38 +/- 14 years; range, 16-73 years) underwent contrast-enhanced turbo
      fast low-angle shot MR angiography. Thirty consecutive coronal 3D slabs with a
      frame rate of 1-second duration were acquired. The mask defined as the first data
      set was subtracted from subsequent images. Image quality was evaluated using a 5
      point scale (from 1, not assessable, to 5, excellent image quality). Twelve
      diagnostic parameters yielded 1 point each in case of correct diagnosis (binary
      analysis into normal or abnormal) and were summarized into three categories:
      anatomy of the main thoracic vessels (maximum, 5 points), sequential cardiac
      anatomy (maximum, 5 points), and shunt detection (maximum, 2 points). The results
      were compared with a combined clinical reference comprising medical or surgical
      reports and other imaging studies. Diagnostic accuracies were calculated for each
      of the parameters as well as for the three categories. RESULTS: The mean image
      quality was 3.7 +/- 1.0. Using a binary approach, 220 (92%) of the 240 single
      diagnostic parameters could be analyzed. The percentage of maximum diagnostic
      points, the sensitivity, the specificity, and the positive and the negative
      predictive values were all 100% for the anatomy of the main thoracic vessels;
      97%, 87%, 100%, 100%, and 96% for sequential cardiac anatomy; and 93%, 93%, 92%,
      88%, and 96% for shunt detection. CONCLUSION: Time-resolved contrast-enhanced MR
      angiography provides, in one breath-hold, anatomic and qualitative functional
      information in adult patients with congenital heart disease. The high diagnostic
      accuracy allows the investigator to tailor subsequent specific MR sequences
      within the same session.

PMID- 16985164
TI  - Incidental findings on integrated PET/CT that do not accumulate 18F-FDG.
AB  - OBJECTIVE: The purpose of this study was to report the prevalence of
      abnormalities that do not show increased 18F-FDG uptake on the CT component of
      integrated PET/CT in patients with non-small cell lung cancer. MATERIALS AND
      METHODS: Images from all PET/CT studies performed consecutively between April and
      October 2003 on patients with non-small cell lung cancer were retrospectively
      reviewed. All abnormalities present on the CT component of the PET/CT scans that
      did not show abnormally increased 18F-FDG uptake were documented. RESULTS: Three
      hundred twenty-one patients with non-small cell lung cancer (179 men, 142 women;
      mean age, 67 years; age range, 38-91 years) underwent initial staging (198/321
      [62%]) or restaging (123/321 [38%]) PET/CT imaging during the study period. In
      263 (82%) of the patients, CT showed 1,231 abnormalities that were not 18F-FDG
      avid. The abnormalities were located in the thorax (n = 650), abdomen and pelvis
      (n = 444), head and neck (n = 69), and bony skeleton (n = 68). In total, 298
      (24%) of the abnormalities that were not 18F-FDG avid were located outside the
      range of a standard thoracic CT scan. The clinical importance of these
      abnormalities was classified as major (n = 48 [4%]), moderate (n = 465 [38%]), or
      minor (n = 718 [58%]). Four (1%) of the patients had findings of major clinical
      importance that did not show increased 18F-FDG uptake and were previously
      unsuspected. CONCLUSION: Among patients with non-small cell lung cancer
      undergoing PET/CT, there is a high prevalence of CT abnormalities that do not
      show correlative 18F-FDG avidity but that may be clinically important.

PMID- 16985165
TI  - PET/CT characterization of fibroosseous defects in children: 18F-FDG uptake can
      mimic metastatic disease.
AB  - OBJECTIVE: The purpose of this study was to characterize the anatomic appearance
      and metabolic activity of nonossifying fibromas, fibrous cortical defects, and
      cortical desmoids on PET/CT images. CONCLUSION: Over a 14-month period, we
      identified eight nonossifying fibromas, four fibrous cortical defects, and two
      cortical desmoids in 330 children who underwent PET/CT for the evaluation of a
      known or suspected malignancy. CT, conventional radiography, MRI, or clinical
      follow-up was used to confirm the diagnoses of these fibroosseous lesions. Eleven
      of the 14 children underwent multiple PET/CT examinations; thus, 34 studies were
      included. The lesions showed variable metabolic activity as indicated by 18F-FDG
      uptake: 19 PET/CT examinations showed lesions with mild 18F-FDG uptake, eight
      showed moderate 18F-FDG uptake, and seven showed intense uptake. When PET reveals
      metabolically active osseous abnormalities in children who are at risk for bone
      metastases, benign fibroosseous lesions should be considered in the differential
      diagnosis before additional diagnostic procedures are undertaken. Benign
      fibroosseous lesions may be metabolically active and thus mimic metastatic
      osseous disease in children with underlying malignancies. Correlative CT or other
      anatomic imaging can confirm the benign nature of these lesions.

PMID- 16985166
TI  - Cl-IB-MECA [2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide] reduces
      ischemia/reperfusion injury in mice by activating the A3 adenosine receptor.
AB  - We used pharmacological agents and genetic methods to determine whether the
      potent A(3) adenosine receptor (AR) agonist 2-chloro-N(6)-(3-iodobenzyl)adenosine
      5'-N-methylcarboxamide (Cl-IB-MECA) protects against myocardial
      ischemia/reperfusion injury in mice via the A(3)AR or via interactions with other
      AR subtypes. Pretreating wild-type (WT) mice with Cl-IB-MECA reduced myocardial
      infarct size induced by 30 min of coronary occlusion and 24 h of reperfusion at
      doses (30 and 100 mug/kg) that concomitantly reduced blood pressure and
      stimulated systemic histamine release. The A(3)AR-selective antagonist MRS 1523
      [3-propyl-6-ethyl-5[(ethylthio)carbonyl]-2-phenyl-4-propyl-3-pyridine
      carboxylate], but not the A(2A)AR antagonist ZM 241385 [4-{2-7-amino-2-(2
      furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl}phenol], blocked the
      reduction in infarct size provided by Cl-IB-MECA, suggesting a mechanism
      involving the A(3)AR. To further examine the selectivity of Cl-IB-MECA, we
      assessed its cardioprotective effectiveness in A(3)AR gene "knock-out" (A(3)KO)
      mice. Cl-IB-MECA did not reduce myocardial infarct size in A(3)KO mice in vivo
      and did not protect isolated perfused hearts obtained from A(3)KO mice from
      injury induced by global ischemia and reperfusion. Additional studies using WT
      mice treated with compound 48/80 [condensation product of p-methoxyphenethyl
      methylamine with formaldehyde] to deplete mast cell contents excluded the
      possibility that Cl-IB-MECA was cardioprotective by releasing mediators from mast
      cells. These data demonstrate that Cl-IB-MECA protects against myocardial
      ischemia/reperfusion injury in mice principally by activating the A(3)AR.

PMID- 16985167
TI  - Block of specific gap junction channel subtypes by 2-aminoethoxydiphenyl borate
      (2-APB).
AB  - 2-Aminoethoxydiphenyl borate (2-APB), an inositol 1,4,5-triphosphate receptor
      modulator, inhibits capacitive current transients measured in normal rat kidney
      and human embryonic kidney 293 cells, an indication of blocking gap junction
      channels between these cells. Here, we used the dual whole-cell patch-clamp
      method to study the actions of 2-APB on gap junction channels formed by selected
      connexins expressed in a communication-deficient neuroblastoma cell line (N2A). 2
      APB dose-dependently and reversibly blocked junctional currents of connexin (Cx)
      50 gap junction channels. The concentration-inhibition curve of 2-APB on the
      junctional current indicated an IC(50) of 3.7 microM, lower than that of most gap
      junction inhibitors. At a concentration of 20 microM, 2-APB also significantly
      blocked junctional conductance in cell pairs coupled by Cx26, Cx30, Cx36, Cx40,
      and Cx45 but did not appreciably affect coupling in cell pairs expressing Cx32,
      Cx43, and Cx46. Although concentration inhibition curves of 2-APB on Cx36
      channels were similar to Cx50 (Cx36; IC(50), 3.0 microM), IC(50) values were
      higher for Cx43 (51.6 microM), Cx45 (18.1 microM), and Cx46 (29.4 microM). The
      blocking action of 2-APB did not substantially alter transjunctional voltage
      dependent gating of Cx50 gap junction channels, and recordings from poorly
      coupled pairs of Cx50-transfected N2A cells indicated that 2-APB reduced gap
      junction channel open probability without changing the main state single-channel
      conductance. The differential efficacy of block by 2-APB of gap junction channels
      formed by different connexins may provide a useful tool that could be exploited
      in gap junction research to selectively block certain gap junction channel
      subtypes.

PMID- 16985168
TI  - Differentiation-specific factors modulate epidermal CYP1-4 gene expression in
      human skin in response to retinoic acid and classic aryl hydrocarbon receptor
      ligands.
AB  - Human epidermal keratinocytes express subsets of cytochromes P450 (P450) (CYP
      gene products) that are strongly up-regulated, not regulated, or down-regulated
      by differentiation-specific factors. We investigated how drug exposure affects
      epidermal expression of CYP1-4 genes, which encode many drug-metabolizing P450s.
      Real-time polymerase chain reaction (PCR) assays measured CYP1-4 mRNA levels in
      epidermal keratinocytes differentiated in vitro in the presence of drug or
      vehicle for 6 days. We confirmed the spinous phenotype at day 6 by changes in
      cellular morphology and upregulation of cytokeratin 10 and transglutaminase
      (TGM)1 mRNA in the differentiating keratinocytes. Effects of drug exposure
      depended on the influence of differentiation-specific factors in controlling
      epidermal CYP1-4 expression. CYP2C18, 2C19, 2C9, 2W1, 3A4, and 4B1 are up
      regulated by cellular differentiation; mRNA levels for these CYP genes were
      inhibited in differentiating keratinocytes exposed to retinoic acid and aryl
      hydrocarbon receptor (AhR) ligands. These same drugs effected <or=2-fold change
      or even augmented mRNA levels for CYP genes that are not regulated by
      differentiation (CYP2S1, 2J2, 1B1, 1A1, 1A2, 2E1, and 2D6) and for CYP2U1, which
      is expressed at highest levels in undifferentiated keratinocytes. The clinically
      relevant drugs miconazole, dexamethasone, rifampicin, and dapsone had little
      effect on CYP1-4 mRNA levels under assay conditions. The AhR ligand 2,3,7,8
      tetrachlorodibenzo-p-dioxin also up-regulated keratinocyte TGM1 mRNA in a
      concentration- and time-dependent manner. This effect was blocked by the AhR
      antagonist resveratrol. These findings implicate AhR-dependent up-regulation of
      TGM1 mRNA in differentiating keratinocytes as one mechanism contributing toward
      chloracne in humans exposed to toxic levels of dioxin.

PMID- 16985169
TI  - Translocation of AT1- and AT2-receptors by higher concentrations of angiotensin
      II in the smooth muscle cells of rat internal anal sphincter.
AB  - Previous studies have reported bimodal effects by angiotensin II (Ang II) in the
      rat internal anal sphincter (IAS), a concentration-dependent contraction (at
      lower concentrations) and relaxation (at higher concentrations). The experiments
      suggest the above-mentioned responses are the result of Ang II subtype I
      receptor(s) (AT(1)-R) and subtype II receptor(s) (AT(2)-R) activation,
      respectively. These studies determined the role and mechanism of AT(2)-R-induced
      relaxation of the smooth muscle cells (SMCs) from the IAS in response to Ang II.
      Laser confocal microscopy showed that in the basal state, the AT(1)-Rs reside in
      the plasma membrane, whereas AT(2)-Rs are present in the cytosol. Higher
      concentrations of Ang II caused movement of AT(1)-R and AT(2)-R in opposite
      directions to the cytosol and the membrane, respectively. Losartan (AT(1)-R
      antagonist) but not S-(+)-1-([4-(dimethylamino)-3-methylphenyl]methyl)-5
      (diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo(4,5-c)pyridine-6-carboxylic acid
      (PD123319; AT(2)-R antagonist) selectively inhibited these movements. These
      results are based on biotinylation assays, confocal images, and Western blot
      analyses of the densities of AT(1)-Rs and AT(2)-Rs in the plasma membrane versus
      cytosolic fractions of the IAS SMCs. Ang II in higher concentrations did not
      change the total contents of Ang II receptors. These data combined with the
      functional data using measurements of IAS SMC lengths suggest that
      internalization of AT(1)-R and externalization of AT(2)-R may be responsible for
      the activation of the AT(2)-R, which leads to the relaxation of the IAS with
      higher concentrations of Ang II.

PMID- 16985170
TI  - Control of coronavirus infection through plasmacytoid dendritic-cell-derived type
      I interferon.
AB  - This study demonstrates a unique and crucial role of plasmacytoid dendritic cells
      (pDCs) and pDC-derived type I interferons (IFNs) in the pathogenesis of mouse
      coronavirus infection. pDCs controlled the fast replicating mouse hepatitis virus
      (MHV) through the immediate production of type I IFNs. Recognition of MHV by pDCs
      was mediated via TLR7 ensuring a swift IFN-alpha production following encounter
      with this cytopathic RNA virus. Furthermore, the particular type I IFN response
      pattern was not restricted to the murine coronavirus, but was also found in
      infection with the highly cytopathic human severe acute respiratory syndrome
      (SARS) coronavirus. Taken together, our results suggest that rapid production of
      type I IFNs by pDCs is essential for the control of potentially lethal
      coronavirus infections.

PMID- 16985171
TI  - Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr
      virus nuclear antigen 1 in healthy virus carriers.
AB  - CD4+ T cells, specific for transforming latent infection with the Epstein Barr
      virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1
      specific effector CD4+ T cells are primarily T-helper 1 (TH1) polarized. Here we
      show that most healthy EBV carriers have such IFN-secreting EBNA1-specific CD4+ T
      cells at a frequency of 0.03% of circulating CD4+ T cells. In addition, healthy
      carriers have a large pool of CD4+ T cells that proliferated in response to EBNA1
      and consisted of distinct memory-cell subsets. Despite continuous antigen
      presence due to persistent EBV infection, half of the proliferating EBNA1
      specific CD4+ T cells belonged to the central-memory compartment (TCM). The
      remaining EBNA1-specific CD4+ T cells displayed an effector-memory phenotype
      (TEM), of which a minority rapidly secreted IFN upon stimulation with EBNA1.
      Based on chemokine receptor analysis, all EBNA1-specific TCM CD4+ T cells were
      TH1 committed. Our results suggest that protective immune control of chronic
      infections, like EBV, includes a substantial reservoir of TCM CD4+ TH1
      precursors, which continuously fuels TH1-polarized effector cells.

PMID- 16985172
TI  - VWF protects FVIII from endocytosis by dendritic cells and subsequent
      presentation to immune effectors.
AB  - Von Willebrand factor (VWF) is a chaperone molecule for procoagulant factor VIII
      (FVIII). Its role in the reduction of the immunogenicity of therapeutic FVIII in
      patients with hemophilia A has been evoked but lacks clear cellular and molecular
      rationale. Here, we demonstrate that VWF protects FVIII from being endocytosed by
      human dendritic cells (DCs) and subsequently presented to FVIII-specific T cells.
      The immunoprotective effect of VWF requires a physical interaction with FVIII
      because the endocytosis of FVIII was significantly restored on hindering the
      formation of the VWF-FVIII complex. Interestingly, VWF had no direct inhibitory
      effect either on the ability of DCs to present antigenic peptides or on the
      activation potency of CD4+ T cells. We thus propose that VWF may reduce the
      immunogenicity of FVIII by preventing, upstream from the activation of immune
      effectors, the entry of FVIII in professional antigen-presenting cells.

PMID- 16985173
TI  - Human mesenchymal stem cells isolated from bone marrow and lymphoid organs
      support tumor B-cell growth: role of stromal cells in follicular lymphoma
      pathogenesis.
AB  - Accumulating evidence indicates that the cellular microenvironment plays a key
      role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes
      (LNs) and in infiltrated bone marrow where ectopic LN-like reticular cells are
      integrated within malignant B-cell nodular aggregates. In normal secondary
      lymphoid organs, specific stromal cell subsets provide a highly specialized
      microenvironment that supports immune response. In particular, fibroblastic
      reticular cells (FRCs) mediate immune cell migration, adhesion, and reciprocal
      interactions. The role of FRCs and their postulated progenitors, that is, bone
      marrow mesenchymal stem cells (MSCs), in FL remains unexplored. In this study, we
      investigated the relationships between FRCs and MSCs and their capacity to
      sustain malignant B-cell growth. Our findings strongly suggest that secondary
      lymphoid organs contain MSCs able to give rise to adipocytes, chondrocytes,
      osteoblasts, as well as fully functional B-cell supportive FRCs. In vitro, bone
      marrow-derived MSCs acquire a complete FRC phenotype in response to a combination
      of tumor necrosis factor-alpha and lymphotoxin-alpha1beta2. Moreover, MSCs
      recruit primary FL cells that, in turn, trigger their differentiation into FRCs,
      making them able to support malignant B-cell survival. Altogether, these new
      insights into the cross talk between lymphoma cells and their microenvironment
      could offer original therapeutic strategies.

PMID- 16985174
TI  - Phenotype and genotype of a cohort of families historically diagnosed with type 1
      von Willebrand disease in the European study, Molecular and Clinical Markers for
      the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD).
AB  - Type 1 von Willebrand disease (VWD) is characterized by a personal and family
      history of bleeding coincident with reduced levels of normal plasma von
      Willebrand factor (VWF). The molecular basis of the disorder is poorly
      understood. The aims of this study were to determine phenotype and genotype and
      their relationship in patients historically diagnosed with type 1 VWD. Families
      were recruited in 9 European countries based on previous type 1 VWD diagnosis.
      Bleeding symptoms were recorded, plasma phenotype analyzed, and VWF mutation
      analysis performed in all index cases (ICs). Phenotypic and molecular analysis
      stratified patients into those with or without phenotypes suggestive of
      qualitative VWF defects (abnormal multimers) and with or without mutations. A
      total of 105 of 150 ICs (70%) had mutations identified. A subgroup with abnormal
      multimers (38% of ICs, 57 of 150) showed a high prevalence of VWF gene mutations
      (95% of ICs, 54 of 57), whereas in those with qualitatively normal VWF, fewer
      mutations were identified (55% of ICs, 51 of 93). About one third of the type 1
      VWD cases recruited could be reconsidered as type 2. The remaining group could be
      considered "true" type 1 VWD, although mutations were found in only 55%.

PMID- 16985175
TI  - Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18:
      characterization of the binding sites on ICAM-4.
AB  - Intercellular adhesion molecule 4 (ICAM-4) is a unique member of the ICAM family
      because of its specific expression on erythroid cells and ability to interact
      with several types of integrins expressed on blood and endothelial cells. The
      first reported receptors for ICAM-4 were CD11a/CD18 and CD11b/CD18. In contrast
      to these 2, the cellular ligands and the functional role of the third beta2
      integrin, CD11c/CD18, have not been well defined. Here, we show that ICAM-4
      functions as a ligand for the monocyte/macrophage-specific CD11c/CD18. Deletion
      of the individual immunoglobulin domains of ICAM-4 demonstrated that both its
      domains contain binding sites for CD11c/CD18. Analysis of a panel of ICAM-4 point
      mutants identified residues that affected binding to the integrin. By molecular
      modeling the important residues were predicted to cluster in 2 distinct but
      spatially close regions of the first domain with an extension to the second
      domain spatially distant from the other residues. We also identified 2 peptides
      derived from sequences of ICAM-4 that are capable of modulating the binding to
      CD11c/CD18. CD11c/CD18 is expressed on macrophages in spleen and bone marrow.
      Inhibition of erythrophagocytosis by anti-ICAM-4 and anti-integrin antibodies
      suggests a role for these interactions in removal of senescent red cells.

PMID- 16985176
TI  - Current concepts on the pathogenesis of the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is an important cause of acquired
      thrombophilia. It is characterized by the core clinical manifestations of
      thrombosis, either venous or arterial, and in women it can also be associated
      with recurrent fetal loss. The detection of persistently elevated levels of
      antiphospholipid antibodies (aPL Abs) is a requisite laboratory feature for the
      diagnosis to be made. The dominant antigenic targets in APS are beta 2
      glycoprotein I (beta2-GPI) and prothrombin. There is an accumulating body of
      experimental evidence that suggests that specific subgroups of aPL Abs may
      directly contribute to disease pathogenesis. This review critically examines the
      experimental evidence underlying the various propositions made to explain how
      these antibodies may predispose to disease in humans. Furthermore, it also
      examines the evidence relating to the immunologic mechanisms that may contribute
      to the breakage of peripheral tolerance in this disorder. Delineating the
      strengths and limitations of the experimental evidence accumulated thus far will
      hopefully stimulate further experimentation toward achieving the ultimate goal of
      precisely defining the dominant pathogenic mechanisms operational in APS. This
      may pave the way for the development of improved therapies.

PMID- 16985177
TI  - Over 20% of patients with chronic lymphocytic leukemia carry stereotyped
      receptors: Pathogenetic implications and clinical correlations.
AB  - The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and
      characterized by the existence of subsets of cases with closely homologous
      ("stereotyped") complementarity-determining region 3 (CDR3) sequences. In the
      present series, 201 (21.9%) of 916 patients with CLL expressed IGHV genes that
      belonged to 1 of 48 different subsets of sequences with stereotyped heavy chain
      (H) CDR3. Twenty-six subsets comprised 3 or more sequences and were considered
      "confirmed." The remaining subsets comprised pairs of sequences and were
      considered "potential"; public database CLL sequences were found to be members of
      9 of 22 "potential" subsets, thereby allowing us to consider them also
      "confirmed." The chance of belonging to a subset exceeded 35% for unmutated or
      selected IGHV genes (eg, IGHV1-69/3-21/4-39). Comparison to non-CLL public
      database sequences showed that HCDR3 restriction is "CLL-related." CLL cases with
      selected stereotyped immunoglobulins (IGs) were also found to share unique
      biologic and clinical features. In particular, cases expressing stereotyped IGHV4
      39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition,
      IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent
      disease, contrasting other patients (eg, those expressing IGHV3-21/IGLV3-21) who
      experienced an aggressive disease, regardless of IGHV mutations. These findings
      suggest that a particular antigen-binding site can be critical in determining the
      clinical features and outcome for at least some CLL patients.

PMID- 16985178
TI  - Incidence of CSF3R mutations in severe congenital neutropenia and relevance for
      leukemogenesis: Results of a long-term survey.
AB  - Point mutations in the gene for the granulocyte colony-stimulating factor (G-CSF)
      receptor CSF3R have been implicated in the progression of severe congenital
      neutropenia (CN) to leukemia. In this study we present data on a total of 218
      patients with chronic neutropenia, including 148 patients with CN (23/148 with
      secondary malignancies). We detected CSF3R nonsense mutations at 17 different
      nucleotide positions (thereof 10 new mutations) which lead to a loss of 1 to all
      4 tyrosine residues in the intracellular domain of the receptor. Of 23 patients
      with CN with signs of malignant transformation, 18 (78%) were shown to harbor a
      CSF3R mutation, indicating that these mutations, although not a necessary
      condition, are highly predictive for malignant transformation even if detected in
      a low percentage of transcripts. In serial analyses of 50 patients with CSF3R
      mutations we were able to follow the clonal dynamics of mutated cells. We could
      demonstrate that even a highly clonal hematopoiesis did not inevitably show a
      rapid progression to leukemia. Our results strongly suggest that acquisition of a
      CSF3R mutation is an early event in leukemogenesis that has to be accompanied by
      cooperating molecular events, which remain to be defined.

PMID- 16985179
TI  - Regulation of dendritic cell migration and adaptive immune response by
      leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and
      function.
AB  - Trafficking of dendritic cells (DCs) to peripheral tissues and to secondary
      lymphoid organs depends on chemokines and lipid mediators. Here, we show that
      bone marrow-derived DCs (BM-DCs) express functional leukotriene B4 (LTB4)
      receptors as observed in dose-dependent chemotaxis and calcium mobilization
      responses. LTB4, at low concentrations, promoted the migration of immature and
      mature DCs to CCL19 and CCL21, which was associated with a rapid (30-minute)
      increase of CCR7 expression at the membrane level. At longer incubation times (6
      hours), gene array analysis revealed a promoting role of LTB4, showing a
      significant increase of CCR7 and CCL19 mRNA levels. BM-DCs cultured from BLT1-/-
      or BLT1/2-/- mice showed a normal phenotype, but in vivo BLT1/2-/-DCs showed
      dramatic decrease in migration to the draining lymph nodes relative to wild-type
      (WT) DCs. Consistent with these observations, BLT1/2-/- mice showed a reduced
      response in a model of 2,4-dinitro-fluorobenzene (DNFB)-induced contact
      hypersensitivity. Adoptive transfer of 2,4-dinitrobenzene sulfonic acid (DNBS)
      pulsed DCs directly implicated the defect in DC migration to lymph node with the
      defect in contact hypersensitivity. These results provide strong evidence for a
      role of LTB4 in regulating DC migration and the induction of adaptive immune
      responses.

PMID- 16985180
TI  - Nitric oxide plays a critical role in suppression of T-cell proliferation by
      mesenchymal stem cells.
AB  - The molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell
      proliferation are poorly understood, and whether a soluble factor plays a major
      role remains controversial. Here we demonstrate that the T-cell-receptor complex
      is not a target for the suppression, suggesting that downstream signals mediate
      the suppression. We found that Stat5 phosphorylation in T cells is suppressed in
      the presence of MSCs and that nitric oxide (NO) is involved in the suppression of
      Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO
      synthase (NOS) was readily detected in MSCs but not T cells, and a specific
      inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell
      proliferation. This production of NO in the presence of MSCs was mediated by CD4
      or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin
      synthase or NOS restored the proliferation of T cells, whereas an inhibitor of
      indoleamine 2,3-dioxygenase and a transforming growth factor-beta-neutralizing
      antibody had no effect. Finally, MSCs from inducible NOS-/- mice had a reduced
      ability to suppress T-cell proliferation. Taken together, these results suggest
      that NO produced by MSCs is one of the major mediators of T-cell suppression by
      MSCs.

PMID- 16985181
TI  - Human CD4+CD25+ regulatory T cells selectively express tyrosine hydroxylase and
      contain endogenous catecholamines subserving an autocrine/paracrine inhibitory
      functional loop.
AB  - CD4+CD25+ regulatory T lymphocytes (Tregs) are specialized T cells playing a key
      role in the control of immune homeostasis. Here, we show that human Tregs
      constitutively express tyrosine hydroxylase (TH, EC 1.14.16.2), the rate-limiting
      enzyme in the synthesis of catecholamines, and contain substantial amounts of
      dopamine, norepinephrine, and epinephrine, which are released upon treatment with
      reserpine. Catecholamine release results in reduced production of interleukin-10
      and transforming growth factor-beta by Tregs, and in down-regulation of Treg
      dependent inhibition of effector T-lymphocyte (Teff) proliferation, which occurs
      without affecting the production of tumor necrosis factor-alpha or interferon
      gamma. Tregs and Teffs express on the cell membrane both D1-like and D2-like
      dopaminergic receptors to a similar extent (12%-29% of the cells). Catecholamine
      dependent down-regulation of Tregs is, however, selectively reversed by
      pharmacological blockade of dopaminergic D1-like receptors, which in Tregs only
      (and not in Teffs) are also expressed at the level of mRNA and are functionally
      coupled to intracellular production of cAMP. These findings indicate that in
      human Tregs endogenous catecholamines subserve an autocrine/paracrine loop
      involving dopaminergic pathways and resulting in down-regulation of Treg
      function.

PMID- 16985183
TI  - Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96
      cases with special reference to the immunophenotypic heterogeneity of CD5.
AB  - Intravascular large B-cell lymphoma (IVLBCL) is pathologically distinct with a
      broad clinical spectrum and immunophenotypic heterogeneity. A series of 96
      patients with IVLBCL (median age, 67 years; range, 41-85 years; 50 men) was
      reviewed. Anemia/thrombocytopenia (84%), hepatosplenomegaly (77%), B symptoms
      (76%), bone marrow involvement (75%), and hemophagocytosis (61%) were frequently
      observed. The International Prognostic Index score was high or high-intermediate
      in 92%. For 62 patients receiving anthracycline-based chemotherapies, median
      survival was 13 months. CD5, CD10, Bcl-6, MUM1, and Bcl-2 were positive in 38%,
      13%, 26%, 95%, and 91% of tumors, respectively. All 59 CD10- IVLBCL cases
      examined were nongerminal center B-cell type because they lacked the Bcl-6+MUM1-
      immunophenotype. CD5 positivity was associated with a higher prevalence of
      marrow/blood involvement and thrombocytopenia and a lower frequency of neurologic
      abnormalities among patients with CD10-IVLBCL. Compared with 97 cases of de novo
      CD5+CD10-diffuse LBCL, 31 cases of CD5+CD10-IVLBCL exhibited higher frequencies
      of poor prognostic parameters, except age. Multivariate analysis in IVLBCL
      revealed that a lack of anthracycline-based chemotherapies (P<.001, hazard ratio
      [HR]: 9.256), age older than 60 years (P=.012, HR: 2.459), and thrombocytopenia
      less than 100x10(9)/L (P=.012, HR: 2.427) were independently unfavorable
      prognostic factors; CD5 positivity was not. Beyond immunophenotypic diversity,
      IVLBCL constitutes a unique group with aggressive behavior.

PMID- 16985182
TI  - Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and
      primitive neuroectodermal tumor of bone: A report from the Children's Oncology
      Group.
AB  - This study describes the magnitude of risk of therapy-related myelodysplasia and
      acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing
      sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091.
      Between 1988 and 1992, patients with or without metastatic disease were
      randomized to receive doxorubicin, vincristine, cyclophosphamide, and
      dactinomycin (regimen A) or these 4 drugs alternating with etoposide and
      ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease
      were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B
      therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide).
      Median age at diagnosis of Ewing sarcoma was 12 years, and median length of
      follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a
      cumulative incidence of 2% at 5 years. While patients treated on regimens A and B
      were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and
      0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold
      increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years),
      when compared with those treated on regimen A. Increasing exposure to ifosfamide
      from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from
      375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.

PMID- 16985184
TI  - Activation of alphaIIbbeta3 is a sufficient but also an imperative prerequisite
      for activation of alpha2beta1 on platelets.
AB  - Platelet integrins alpha2beta1 and alphaIIbbeta3 play critical roles in platelet
      adhesion and thrombus formation after vascular injury. On resting platelets, both
      integrins are in a low-affinity state. However, agonist stimulation results in
      conformational changes that enable ligand binding that can be detected with
      conformation dependent monoclonal antibodies (mAbs). By using such conformation
      dependent mAbs, we could demonstrate that activation of integrin alphaIIbbeta3 is
      not only sufficient, but also a prerequisite for alpha2beta1 activation. Compared
      with platelets in plasma, stimulation of washed platelets resulted in only a
      minor activation of alpha2beta1, as detected with the activation-sensitive mAb
      IAC-1. Addition of fibrinogen to stimulated washed platelets greatly potentiated
      activation of this integrin. Also, treatment of alphaIIbbeta3 with the ligand
      mimetic peptide RGDS, resulting in outside-in signaling, led to a powerful
      alpha2beta1 activation, even in the absence of overall platelet activation,
      involving tyrosine kinase activity but no protein kinase C activation. The
      absolute necessity of alphaIIbbeta3 for proper alpha2beta1 activation on
      platelets was demonstrated by using the alphaIIbbeta3 antagonist aggrastat, which
      was able to completely abolish alpha2beta1 activation, both under static and flow
      conditions. In addition, analogous experiments with Glanzmann platelets lacking
      alphaIIbbeta3 confirmed the indispensability of alphaIIbbeta3 for alpha2beta1
      activation.

PMID- 16985185
TI  - Ginsenoside Re, a main phytosterol of Panax ginseng, activates cardiac potassium
      channels via a nongenomic pathway of sex hormones.
AB  - Ginseng root is one of the most popular herbs throughout the world and is
      believed to be a panacea and to promote longevity. It has been used as a medicine
      to protect against cardiac ischemia, a major cause of death in the West. We have
      previously demonstrated that ginsenoside Re, a main phytosterol of Panax ginseng,
      inhibits Ca(2+) accumulation in mitochondria during cardiac ischemia/reperfusion,
      which is attributable to nitric oxide (NO)-induced Ca(2+) channel inhibition and
      K(+) channel activation in cardiac myocytes. In this study, we provide compelling
      evidence that ginsenoside Re activates endothelial NO synthase (eNOS) to release
      NO, resulting in activation of the slowly activating delayed rectifier K(+)
      current. The eNOS activation occurs via a nongenomic pathway of each of androgen
      receptor, estrogen receptor-alpha, and progesterone receptor, in which c-Src,
      phosphoinositide 3-kinase, Akt, and eNOS are sequentially activated. However,
      ginsenoside Re does not stimulate proliferation of androgen-responsive LNCaP
      cells and estrogen-responsive MCF-7 cells, implying that ginsenoside Re does not
      activate a genomic pathway of sex hormone receptors. Fluorescence resonance
      energy transfer experiments with a probe, SCCoR (single cell coactivator
      recruitment), indicate that the lack of genomic action is attributable to failure
      of coactivator recruitment. Thus, ginsenoside Re acts as a specific agonist for
      the nongenomic pathway of sex steroid receptors, and NO released from activated
      eNOS underlies cardiac K(+) channel activation and protection against ischemia
      reperfusion injury.

PMID- 16985186
TI  - The mechanism of activity-dependent sodium channel inhibition by the
      antidepressants fluoxetine and desipramine.
AB  - The effect of monoamine uptake inhibitor-type antidepressants on sodium channels
      of hippocampal neurons was investigated. Members of the tricyclic group of
      antidepressants are known to modify multiple targets, including sodium channels,
      whereas selective serotonin-reuptake inhibitors (SSRIs) are regarded as highly
      selective compounds, and their effect on sodium channels was not investigated in
      detail. In this study, a representative member of each group was chosen: the
      tricyclic antidepressant desipramine and the SSRI fluoxetine. The drugs were
      roughly equipotent use-dependent inhibitors of sodium channels, with IC(50)
      values approximately 100 microM at -150 mV holding potential, and approximately 1
      microM at -60 mV. We suggest that therapeutic concentrations of antidepressants
      affect neuronal information processing partly by direct, activity-dependent
      inhibition of sodium channels. As for the mechanism of inhibition, use-dependent
      inhibition by antidepressants was believed to be due to a preferential affinity
      to the fast-inactivated state. Using a voltage and perfusion protocol by which
      relative affinities to fast-versus slow-inactivated states could be assessed, we
      challenged this view and found that the affinity of both drugs to slowinactivated
      state(s) was higher. We propose a different mechanism of action for these
      antidepressants, in which slow rather than fast inactivation plays the dominant
      role. This mechanism is similar but not equivalent with the novel mechanism of
      usedependent sodium channel inhibition previously described by our group
      (Neuroscience 125:1019-1028, 2004; Neuroreport 14:1945-1949, 2003). Our results
      suggest that different drugs can produce use-dependent sodium channel inhibition
      by different mechanisms.

PMID- 16985187
TI  - Locomotion by Abdopus aculeatus (Cephalopoda: Octopodidae): walking the line
      between primary and secondary defenses.
AB  - Speeds and variation in body form during crawling, bipedal walking, swimming and
      jetting by the shallow-water octopus Abdopus aculeatus were compared to explore
      possible interactions between defense behaviors and biomechanics of these multi
      limbed organisms. General body postures and patterns were more complex and varied
      during the slow mode of crawling than during fast escape maneuvers such as
      swimming and jetting. These results may reflect a trade-off between predator
      deception and speed, or simply a need to reduce drag during jet-propelled
      locomotion. Octopuses swam faster when dorsoventrally compressed, a form that may
      generate lift, than when swimming in the head-raised posture. Bipedal locomotion
      proceeded as fast as swimming and can be considered a form of fast escape
      (secondary defense) that also incorporates elements of crypsis and polyphenism
      (primary defenses). Body postures during walking suggested the use of both static
      and dynamic stability. Absolute speed was not correlated with body mass in any
      mode. Based on these findings the implications for defense behaviors such as
      escape from predation, aggression, and 'flatfish mimicry' performed by A.
      aculeatus and other octopuses are discussed.

PMID- 16985188
TI  - Pectoral fin coordination and gait transitions in steadily swimming juvenile reef
      fishes.
AB  - A common feature of animal locomotion is its organization into gaits with
      distinct patterns of movement and propulsor use for specific speeds. In
      terrestrial vertebrates, limb gaits have been extensively studied in diverse taxa
      and gait transitions have been shown to provide efficient locomotion across a
      wide range of speeds. In contrast, examination of gaits in fishes has focused on
      axial gaits and the transition between synchronous paired fin locomotion and
      axial propulsion. Because many fishes use their pectoral fins as their primary
      propulsors, we aimed to examine more broadly the use of pectoral fin gaits in
      locomotion. We used juvenile reef fishes in these experiments because their
      swimming could be recorded readily across a wide range of Reynolds numbers, which
      we thought would promote gait diversity. Based on previous work in larval fishes,
      we hypothesized that juveniles have alternating pectoral fin movements rather
      than the synchronous, or in-phase, coordination pattern of adults. In flow tank
      swim studies, we found that juvenile sapphire damselfish Pomacentrus pavo used
      two fin gaits during steady swimming. Below approximately 3 BL s(-1), P. pavo
      primarily swam with alternating fin strokes 180 degrees out of phase with one
      another. At speeds in the range of 3-4 BL s(-1), they performed a gait transition
      to synchronous fin coordination. Between approximately 4 and 8 BL s(-1), P. pavo
      primarily beat their fins synchronously. At around 8 BL s(-1) there was another
      gait transition to body-caudal fin swimming, in which the pectoral fins were
      tucked against the body. We suggest that the transition from alternating to
      synchronous fin coordination occurs due to mechanical limits of gait performance
      rather than to energy efficiency, stability or transitions in hydrodynamic
      regime. To determine whether this gait transition was species-specific, we
      surveyed pectoral fin locomotion in juveniles from 11 species in three reef fish
      families (Pomacentridae, Labridae and Scaridae). We found that this gait
      transition occurred in every species examined, suggesting that it may be a common
      behavior of juvenile reef fishes. Greater inclusion of early life history stages
      in the study of fin-based locomotion should significantly enhance and inform the
      growing body of work on these behaviors.

PMID- 16985189
TI  - Dietary acidification enhances phosphorus digestibility but decreases H+/K+
      ATPase expression in rainbow trout.
AB  - Oxynticopeptic cells of fish stomach are thought to secrete less acid than the
      specialized parietal cells of mammalian stomach. Gastric acidity, however, has
      not been directly compared between fish and mammals. We therefore fed rainbow
      trout and rats the same meal, and found that the lowest postprandial pH of trout
      stomach was 2.7, which was only transiently sustained for 1 h, whereas that of
      rat stomach was 1.3, which was sustained for 3 h. Postprandial pH of the small
      intestine was slightly higher in trout (approximately 8.0) than in rats
      (approximately 7.6), but pH of the large intestine was similar (approximately
      8.0). Addition of acids to fish feeds, in an attempt to aid the weak acidity of
      fish stomach, has been known to improve phosphorus digestibility, but its
      physiological effect on fish stomach is not known. Exogenous acids did improve
      phosphorus digestibility but also decreased steady-state mRNA expression of trout
      H(+)/K(+)-ATPase (ATP4A, the proton pump) as well as Na(+)/bicarbonate
      cotransporter (NBC), and had no effect on gastrin-like mRNA and somastostatin
      (SST) mRNA abundance. Gastrin-like mRNA and SST-2 mRNA were equally distributed
      between corpus and antrum. ATP4A mRNA and NBC mRNA were in the corpus, whereas
      SST-1 mRNA was in the antrum. Trout gastrin-like EST had modest homology to
      halibut and pufferfish gastrin, whereas trout ATP4A mRNA had > or = 95% amino
      acid homology with mammalian, Xenopus and flounder ATP4A. Although ATP4A seems
      highly conserved among vertebrates, gastric acidity is much less in trout than in
      rats, explaining the low digestibility of bone phosphorus, abundant in fish
      diets. Dietary acidification does not reduce acidity enough to markedly improve
      phosphorus digestibility, perhaps because exogenous acids may inhibit endogenous
      acid production.

PMID- 16985190
TI  - Receptor expression and sympatric speciation: unique olfactory receptor neuron
      responses in F1 hybrid Rhagoletis populations.
AB  - The Rhagoletis pomonella species complex is one of the foremost examples
      supporting the occurrence of sympatric speciation. A recent study found that
      reciprocal F(1) hybrid offspring from different host plant-infesting populations
      in the complex displayed significantly reduced olfactory host preference in
      flight-tunnel assays. Behavioral and electrophysiological studies indicate that
      olfactory cues from host fruit are important chemosensory signals for flies to
      locate fruit for mating and oviposition. The reduced olfactory abilities of
      hybrids could therefore constitute a significant post-mating barrier to gene flow
      among fly populations. The present study investigated the source of changes in
      the hybrid olfactory system by examining peripheral chemoreception in F(1) hybrid
      flies, using behaviorally relevant volatiles from the parent host fruit. Single
      sensillum electrophysiological analyses revealed significant changes in olfactory
      receptor neuron (ORN) response specificities in hybrid flies when compared to
      parent ORN responses. We report that flies from F(1) crosses of apple-, hawthorn-
      and flowering dogwood-origin populations of R. pomonella exhibited distinct ORN
      response profiles absent from any parent population. These peripheral alterations
      in ORN response profiles could result from misexpression of multiple receptors in
      hybrid neurons as a function of genomic incompatibilities in receptor-gene
      pathways in parent populations. We conclude that these changes in peripheral
      chemoreception could impact olfactory host preference and contribute directly to
      reproductive isolation in the Rhagoletis complex, or could be genetically coupled
      to other host-associated traits.

PMID- 16985191
TI  - Centre of mass movement and mechanical energy fluctuation during gallop
      locomotion in the Thoroughbred racehorse.
AB  - During locomotion cyclical interchange between different forms of mechanical
      energy enhances economy; however, 100% efficiency cannot be achieved and
      ultimately some mechanical work must be performed de novo. There is a metabolic
      cost associated with fluctuations in mechanical energy, even in the most
      efficient animals. In this study we investigate the exchanges between different
      forms of mechanical energy involved in high-speed gallop locomotion in
      Thoroughbred race horses during over-ground locomotion using innovative, mobile
      data collection techniques. We use hoof-mounted accelerometers to capture foot
      contact times, a GPS data logger to monitor speed and an inertial sensor mounted
      over the dorsal spinous processes of the fourth to sixth thoracic vertebrae (the
      withers) of the horse to capture trunk movement with six degrees of freedom.
      Trunk movement data were used to estimate the movement of the centre of mass
      (CoM). Linear (craniocaudal, mediolateral and dorsoventral) and rotational (roll,
      pitch and heading) kinematic parameters (displacement, velocity and acceleration)
      were calculated for seven horses at gallop speeds ranging from 7 to 17 m s(-1)
      during their regular training sessions. These were used to estimate external
      mechanical energy (potential energy and linear kinetic energy of the CoM) as well
      as selected components of internal energy (angular kinetic energy). Elastic
      energy storage in the limbs was estimated from duty factor, sine wave assumptions
      and published leg stiffness values. External mechanical energy changes were
      dominated by changes in craniocaudal velocity. Potential energy change, which was
      in phase with craniocaudal energy during the front limb stances, was small.
      Elastic energy storage in the limbs was small compared to the overall amplitude
      of fluctuation of external mechanical energy. Galloping at high speeds does not
      therefore fit classical spring mass mechanics.

PMID- 16985192
TI  - The spectral sensitivity of the lens eyes of a box jellyfish, Tripedalia
      cystophora (Conant).
AB  - Box jellyfish, or cubomedusae (class Cubozoa), are unique among the Cnidaria in
      possessing lens eyes similar in morphology to those of vertebrates and
      cephalopods. Although these eyes were described over 100 years ago, there has
      been no work done on their electrophysiological responses to light. We used an
      electroretinogram (ERG) technique to measure spectral sensitivity of the lens
      eyes of the Caribbean species Tripedalia cystophora. The cubomedusae have two
      kinds of lens eyes, the lower and upper lens eyes. We found that both lens eye
      types have similar spectral sensitivities, which likely result from the presence
      of a single receptor type containing a single opsin. The peak sensitivity is to
      blue-green light. Visual pigment template fits indicate a vitamin A-1 based opsin
      with peak sensitivity near 500 nm for both eye types.

PMID- 16985193
TI  - Feeding and digestion in low salinity in an osmoconforming crab, Cancer gracilis.
      I. Cardiovascular and respiratory responses.
AB  - The osmoregulatory physiology of decapod crustaceans has received extensive
      attention. Within this field there is a growing body of literature on
      cardiovascular and respiratory responses to low salinity. Most species exhibit a
      tachycardia coupled with an increase in ventilation rate and oxygen uptake.
      However, these previous experiments were conducted on animals that were starved
      prior to experimentation in order to avoid increases in metabolism associated
      with digestive processes. Because organisms are not necessarily starved prior to
      experiencing environmental perturbations, results from previous experiments may
      not represent natural physiological responses. The present study investigated how
      an osmoconforming decapod, the graceful crab Cancer gracilis, balanced the
      demands of physiological systems (prioritization or additivity of events) during
      feeding and digestion in a low salinity environment. Cancer gracilis exhibited a
      typical increase in oxygen uptake and less pronounced increases in cardiovascular
      variables (heart rate, stroke volume, cardiac output) during feeding in 100%
      seawater. In 3-day starved crabs, exposure to 65% seawater resulted in a
      pronounced bradycardia, with a concomitant decrease in cardiac output and
      haemolymph flow rates and a temporary decrease in oxygen uptake. When crabs were
      exposed to low salinity, 3 h and 24 h after food ingestion, heart rate increased
      slightly and cardiac output and ventilation rates remained stable. Although
      oxygen uptake decreased transiently, feeding levels were quickly regained. During
      a recovery phase in 100%SW there was an overshoot in parameters, suggesting
      repayment of an oxygen debt. Thus, it appears that feeding and digestion are
      prioritized in this species, allowing it to survive acute exposure to hyposaline
      water. Furthermore, the results show that the nutritional state of an animal is
      important in modulating its physiological responses to environmental
      perturbations. This underscores the importance of studying physiological
      responses at the whole organism level under conditions closely approximating
      those of the natural environment.

PMID- 16985194
TI  - Feeding and digestion in low salinity in an osmoconforming crab, Cancer gracilis.
      II. Gastric evacuation and motility.
AB  - Gastric evacuation and gut contraction rates were followed in the graceful crab
      Cancer gracilis during exposure to low salinity. Crabs were fed a radio-opaque
      meal and then exposed to 100% seawater (SW), 80%SW or 60%SW; passage of digesta
      was followed using a fluoroscope. Exposure to low salinity increased the time for
      food passage through the gut system. Times for emptying of the foregut, midgut
      and hindgut varied in a dose-dependent manner. In the lowest salinity, crabs
      regurgitated food from the foregut after approximately 6 h. This may act as a
      protective response, clearing the gut and avoiding subsequent increases in
      metabolism associated with digestion. Contraction rate of the cardiac stomach and
      gastric mill was sporadic and there was no significant change with salinity. In
      contrast, contractions of the pyloric region were more constant and rapid.
      Pyloric contractions decreased at each salinity within 2-4 h after feeding.
      Contraction rates of the pyloric chamber were significantly lower in 60%SW
      compared with 100%SW and 80%SW. During a salinity cycle there was also slowing of
      gut contractions and food passage through the gut system. Pre-treatment levels
      were only regained slowly when the animals were returned to 100%SW. Cancer
      gracilis was able to slow digestion during low salinity exposure, which may spare
      resources for other systems. However, the crabs could not halt digestion
      completely and may be committed to protein synthesis once intracellular digestion
      has begun.

PMID- 16985195
TI  - Tests of absolute photorefractoriness in four species of cardueline finch that
      differ in reproductive schedule.
AB  - Species with different reproductive schedules may differ in how they respond to
      the annual change in photoperiod (the adaptive specialization hypothesis).
      Seasonally breeding species are predicted to use photorefractoriness to terminate
      reproduction prior to inclement conditions in autumn and winter, whereas
      opportunistically breeding species may not exhibit photorefractoriness. We tested
      for absolute photorefractoriness in four species of cardueline finch that differ
      in their reproductive schedules: opportunistically breeding red crossbills,
      flexibly breeding pine siskins, and seasonally breeding Cassin's finches and gray
      crowned rosy-finches. Field observations indicated that all four species regress
      their gonads and begin prebasic feather molt in late summer or autumn. However,
      exposure to a long day photoperiod in autumn (24 h:0 h L:D) resulted in elevation
      of gonadotropins and testicular recrudescence in all species except Cassin's
      finches. Thus, by this criterion, some of the seasonally breeding species tested
      here did not exhibit absolute photorefractoriness. These results indicate that
      phylogenetic history needs to be taken into account when considering the adaptive
      nature of photoperiod response systems.

PMID- 16985196
TI  - The hydrocarbon seep tubeworm Lamellibrachia luymesi primarily eliminates sulfate
      and hydrogen ions across its roots to conserve energy and ensure sulfide supply.
AB  - Lamellibrachia luymesi (Polychaeta, Siboglinidae) is a deep-sea vestimentiferan
      tubeworm that forms large bush-like aggregations at hydrocarbon seeps in the Gulf
      of Mexico. Like all vestimentiferans, L. luymesi obtains its nutrition from
      sulfide-oxidizing endosymbiotic bacteria, which it houses in an internal organ
      called the trophosome. This tubeworm has a lifespan of over 170 years and its
      survival is contingent upon the availability of sulfide during this long period.
      In sediments underlying L. luymesi aggregations, microbes produce sulfide by
      coupling sulfate reduction with hydrocarbon oxidation. L. luymesi acquires
      sulfide from the sediment using a root-like posterior extension of its body that
      is buried in the sediment. Its symbionts then oxidize the sulfide to produce
      energy for carbon fixation, and release sulfate and hydrogen ions as byproducts.
      It is critical for the tubeworm to eliminate these waste ions, and it could do so
      either across its vascular plume or across its root. In this study, we measured
      sulfate and proton elimination rates from live L. luymesi and found that they
      eliminated approximately 85% of the sulfate produced by sulfide oxidation, and
      approximately 67% of the protons produced by various metabolic processes, across
      their roots. On the basis of experiments using membrane transport inhibitors, we
      suggest that L. luymesi has anion exchangers that mediate sulfate elimination
      coupled with bicarbonate uptake. Roots could be the ideal exchange surface for
      eliminating sulfate and hydrogen ions for two reasons. First, these ions might be
      eliminated across the root epithelium using facilitated diffusion, which is
      energetically economical. Second, sulfate and hydrogen ions are substrates for
      bacterial sulfate reduction, and supplying these ions into the sediment might
      help ensure a sustained sulfide supply for L. luymesi over its entire lifespan.

PMID- 16985197
TI  - The expression level of frog relaxin mRNA (fRLX), in the testis of Rana
      esculenta, is influenced by testosterone.
AB  - Frog relaxin (fRLX) belongs to the relaxin/insulin gene family present in the
      testis of Rana esculenta and is specifically expressed by Leydig cells. Since the
      expression of fRLX transcript changes during the reproductive cycle and is more
      abundant when circulating levels of androgens are relatively high, we
      investigated the effect(s) of testosterone and its antagonist (cyproterone
      acetate, CPA) on its expression pattern, in the testis of the frog Rana
      esculenta. Results from in vivo and in vitro experiments demonstrate that
      testosterone strongly induces a significant increase of fRLX mRNA expression in
      frog testes and, this effect is counteracted by CPA, supporting the existence of
      intratesticular (autocrine/paracrine) mechanisms of action. Interestingly, in
      both the control and testosterone-treated testes, fRLX mRNA expression was
      markedly decreased 24 h post-treatment, as compared to that measured at 2 h and 8
      h post-treatment, suggesting that factor(s), other than testosterone, may act(s)
      in controlling its expression. In addition, RT-PCR analysis and in situ
      hybridization performed on frog testis injected with CPA for 15 days, on
      alternate days, showed a strong decrease of fRLX expression, suggesting that CPA
      counteracts the effect of testosterone on fRLX expression. Taken together our
      results strongly indicate that changes in the production, by the Leydig cells, of
      both testosterone and fRLX may represent a marker for the study of Leydig cell
      activity in the testis of the frog Rana esculenta.

PMID- 16985198
TI  - The locomotor kinematics of Asian and African elephants: changes with speed and
      size.
AB  - For centuries, elephant locomotion has been a contentious and confusing challenge
      for locomotion scientists to understand, not only because of technical
      difficulties but also because elephant locomotion is in some ways atypical of
      more familiar quadrupedal gaits. We analyzed the locomotor kinematics of over
      2400 strides from 14 African and 48 Asian elephant individuals (body mass 116
      4632 kg) freely moving over ground at a 17-fold range of speeds, from slow
      walking at 0.40 m s(-1) to the fastest reliably recorded speed for elephants, 6.8
      m s(-1). These data reveal that African and Asian elephants have some subtle
      differences in how size-independent kinematic parameters change with speed.
      Although elephants use a lateral sequence footfall pattern, like many other
      quadrupeds, they maintain this footfall pattern at all speeds, shifting toward a
      25% phase offset between limbs (singlefoot) as they increase speed. The duty
      factors of elephants are greater for the forelimbs than for the hindlimbs, so an
      aerial phase for the hindquarters is reached at slower speeds than for the
      forequarters. This aerial phase occurs at a Froude number of around 1, matching
      theoretical predictions. At faster speeds, stance and swing phase durations
      approach asymptotes, with the duty factor beginning to level off, concurrent with
      an increase in limb compliance that likely keeps peak forces relatively low. This
      increase of limb compliance is reflected by increased compression of the
      hindlimbs. Like other tetrapods, smaller elephants are relatively more athletic
      than larger ones, but still move very similarly to adults even at <500 kg. At any
      particular speed they adopt greater relative stride frequencies and relative
      stride lengths compared to larger elephants. This extends to near-maximal
      locomotor performance as well - smaller elephants reach greater Froude numbers
      and smaller duty factors, hence likely reach relatively greater peak loads on
      their limbs and produce this force more rapidly. A variety of lines of kinematic
      evidence support the inference that elephants change their mechanics near a
      Froude number of 1 (if not at slower speeds), at least to using more compliant
      limbs, if not spring-like whole-body kinetics. In some ways, elephants move
      similarly to many other quadrupeds, such as increasing speed mainly by increasing
      stride frequency (except at fast speeds), and they match scaling predictions for
      many stride parameters. The main difference from most other animals is that
      elephants never change their footfall pattern to a gait that uses a whole-body
      aerial phase. Our large dataset establishes what the normal kinematics of
      elephant locomotion are, and can also be applied to identify gait abnormalities
      that may signal musculoskeletal pathologies, a matter of great importance to
      keepers of captive elephants.

PMID- 16985199
TI  - Lifetime performance in foraging honeybees: behaviour and physiology.
AB  - Honeybees, Apis mellifera, gradually increase their rate of forage uptake as they
      gain foraging experience. This increase in foraging performance has been proposed
      to occur as a result of learning; however, factors affecting flight ability such
      as changes in physiological components of flight metabolism could also contribute
      to this pattern. Thus, the purpose of this study was to assess the contribution
      of physiological changes to the increase in honeybee foraging performance. We
      investigated aspects of honeybee flight muscle biochemistry throughout the adult
      life, from non-foraging hive bees, through young and mature foragers, to old
      foragers near the end of their lifespan. Two-dimensional gel proteomic analysis
      on honeybee thorax muscle revealed an increase in several proteins from hive bees
      to mature foragers including troponin T 10a, aldolase and superoxide dismutase.
      By contrast, the activities (V(max)) of enzymes involved in aerobic performance,
      phosphofructokinase, hexokinase, pyruvate kinase and cytochrome c oxidase, did
      not increase in the flight muscles of hive bees, young foragers, mature foragers
      and old foragers. However, citrate synthase activity was found to increase with
      foraging experience. Hence, our results suggest plasticity in both structural and
      metabolic components of flight muscles with foraging experience.

PMID- 16985200
TI  - Membrane lipid physiology and toxin catabolism underlie ethanol and acetic acid
      tolerance in Drosophila melanogaster.
AB  - Drosophila melanogaster has evolved the ability to tolerate and utilize high
      levels of ethanol and acetic acid encountered in its rotting-fruit niche.
      Investigation of this phenomenon has focused on ethanol catabolism, particularly
      by the enzyme alcohol dehydrogenase. Here we report that survival under ethanol
      and acetic acid stress in D. melanogaster from high- and low-latitude populations
      is an integrated consequence of toxin catabolism and alteration of physical
      properties of cellular membranes by ethanol. Metabolic detoxification contributed
      to differences in ethanol tolerance between populations and acclimation
      temperatures via changes in both alcohol dehydrogenase and acetyl-CoA synthetase
      mRNA expression and enzyme activity. Independent of changes in ethanol
      catabolism, rapid thermal shifts that change membrane fluidity had dramatic
      effects on ethanol tolerance. Cold temperature treatments upregulated
      phospholipid metabolism genes and enhanced acetic acid tolerance, consistent with
      the predicted effects of restoring membrane fluidity. Phospholipase D was
      expressed at high levels in all treatments that conferred enhanced ethanol
      tolerance, suggesting that this lipid-mediated signaling enzyme may enhance
      tolerance by sequestering ethanol in membranes as phophatidylethanol. These
      results reveal new candidate genes underlying toxin tolerance and membrane
      adaptation to temperature in Drosophila and provide insight into how interactions
      between these phenotypes may underlie the maintenance of latitudinal clines in
      ethanol tolerance.

PMID- 16985201
TI  - Effects of long-term hypoxia on enzymes of carbohydrate metabolism in the Gulf
      killifish, Fundulus grandis.
AB  - The goal of the current study was to generate a comprehensive, multi-tissue
      perspective of the effects of chronic hypoxic exposure on carbohydrate metabolism
      in the Gulf killifish Fundulus grandis. Fish were held at approximately 1.3 mg l(
      1) dissolved oxygen (approximately 3.6 kPa) for 4 weeks, after which maximal
      activities were measured for all glycolytic enzymes in four tissues (white
      skeletal muscle, liver, heart and brain), as well as for enzymes of glycogen
      metabolism (in muscle and liver) and gluconeogenesis (in liver). The specific
      activities of enzymes of glycolysis and glycogen metabolism were strongly
      suppressed by hypoxia in white skeletal muscle, which may reflect decreased
      energy demand in this tissue during chronic hypoxia. In contrast, several enzyme
      specific activities were higher in liver tissue after hypoxic exposure,
      suggesting increased capacity for carbohydrate metabolism. Hypoxic exposure
      affected fewer enzymes in heart and brain than in skeletal muscle and liver, and
      the changes were smaller in magnitude, perhaps due to preferential perfusion of
      heart and brain during hypoxia. The specific activities of some gluconeogenic
      enzymes increased in liver during long-term hypoxic exposure, which may be
      coupled to increased protein catabolism in skeletal muscle. These results
      demonstrate that when intact fish are subjected to prolonged hypoxia, enzyme
      activities respond in a tissue-specific fashion reflecting the balance of
      energetic demands, metabolic role and oxygen supply of particular tissues.
      Furthermore, within glycolysis, the effects of hypoxia varied among enzymes,
      rather than being uniformly distributed among pathway enzymes.

PMID- 16985202
TI  - Identification and developmental expression of mRNAs encoding crustacean
      cardioactive peptide (CCAP) in decapod crustaceans.
AB  - Full-length cDNAs encoding crustacean cardioactive peptide (CCAP) were isolated
      from several decapod (brachyuran and astacuran) crustaceans: the blue crab
      Callinectes sapidus, green shore crab Carcinus maenas, European lobster Homarus
      gamarus and calico crayfish Orconectes immunis. The cDNAs encode open reading
      frames of 143 (brachyurans) and 139-140 (astacurans) amino acids. Apart from the
      predicted signal peptides (30-32 amino acids), the conceptually translated
      precursor codes for a single copy of CCAP and four other peptides that are
      extremely similar in terms of amino acid sequence within these species, but which
      clearly show divergence into brachyuran and astacuran groups. Expression patterns
      of CCAP mRNA and peptide were determined during embryonic development in Carcinus
      using quantitative RT-PCR and immunohistochemistry with whole-mount confocal
      microscopy, and showed that significant mRNA expression (at 50% embryonic
      development) preceded detectable levels of CCAP in the developing central nervous
      system (CNS; at 70% development). Subsequent CCAP gene expression dramatically
      increased during the late stages of embryogenesis (80-100%), coincident with
      developing immunopositive structures. In adult crabs, CCAP gene expression was
      detected exclusively in the eyestalk, brain and in particular the thoracic
      ganglia, in accord with the predominance of CCAP-containing cells in this tissue.
      Measurement of expression patterns of CCAP mRNA in Carcinus and Callinectes
      thoracic ganglia throughout the moult cycle revealed only modest changes,
      indicating that previously observed increases in CCAP peptide levels during
      premoult were not transcriptionally coupled. Severe hypoxic conditions resulted
      in rapid downregulation of CCAP transcription in the eyestalk, but not the
      thoracic ganglia in Callinectes, and thermal challenge did not change CCAP mRNA
      levels. These results offer the first tantalising glimpses of involvement of CCAP
      in environmental adaptation to extreme, yet biologically relevant stressors, and
      perhaps suggest that the CCAP-containing neurones in the eyestalk might be
      involved in adaptation to environmental stressors.

PMID- 16985203
TI  - Growth or differentiation? Adaptive regeneration in the brittlestar Amphiura
      filiformis.
AB  - Amphiura filiformis is a burrowing brittlestar, which extends arms in the water
      column when suspension feeding. In previous studies, unexpectedly high
      variability was observed in regeneration rate between individuals even when
      experiments were performed under identical conditions. The aims of this work were
      to understand this variability and interpret the observed variability in terms of
      adaptation to sublethal predation. Our experiments on the dynamics of arm
      regeneration in A. filiformis revealed that the developmental program during
      regeneration is well adapted to its burrowing life style. We demonstrate that
      there is a trade-off between regeneration in length and functional recovery for
      feeding (differentiation index). The amount of tissue lost (length lost), which
      represents the quantity of tissue needed to completely regenerate an intact arm
      with no previous history of regeneration, determines whether the arm will invest
      more energy in growth and/or in differentiation, which must be a reflection of
      the ability to differentially regulate developmental programs during
      regeneration. We show that combining regeneration rate with differentiation index
      provides an ideal tool for the definition of a standard temporal framework for
      both field and laboratory studies of regeneration.

PMID- 16985204
TI  - Laboratory behavioural assay of insect magnetoreception: magnetosensitivity of
      Periplaneta americana.
AB  - A relatively simple all-laboratory behavioural assay of insect magnetoreception
      has been developed. We found non-conditioned reactions of American cockroach to
      the periodical shifts of the geomagnetic field. The movement activity of animals
      individually placed into Petri dishes was scored as a number of body turns. Test
      groups were exposed to a 90-min interval with the horizontal component of the
      geomagnetic field periodically rotated by 60 degrees back and forth with 5 min
      periodicity. The number of body turns was compared with the preceding and
      following intervals and with the corresponding interval of the control group kept
      in the natural field. We obtained a significant increase in activity when changes
      in field were applied. Interestingly, the period of increased activity did not
      coincide precisely with the 90 min stimulation interval. The onset of animal
      restlessness was delayed by tens of minutes and persisted correspondingly after
      the stimulation stopped. A respective evaluation criterion was suggested and
      verified. Owing to its simplicity and minimal manipulation of the insects,
      together with low demands on the memory and motivation state of animals, the
      approach potentially may be used as a laboratory diagnostic tool indicating
      magnetoreception in insect neurophysiology research.

PMID- 16985205
TI  - Wing beat kinematics of a nectar-feeding bat, Glossophaga soricina, flying at
      different flight speeds and Strouhal numbers.
AB  - High-speed film analysis showed that the wing beat kinematics in Glossophaga
      soricina change gradually with increasing flight speed, indicating that there is
      no sudden gait change at any particular, critical, flight speed. The flight of
      two adult specimens was studied over a range of flight speeds (1.23-7.52 ms(-1))
      in a 30 m long flight tunnel. During the upstroke in hovering and slow flight
      there is a tip-reversal or supination of the handwings, which thus produce a
      backward flick. This backward motion successively disappears at speeds V
      approximately 3.2 ms(-1), above which the wingtip path becomes more vertical or
      directed upwards-forwards relative to the still air (the stroke plane angle
      increasing with flight speed as alpha=44.8V(0.29)). We found no correlations
      between either span ratio SR (the ratio of the wing span on the upstroke to that
      on the downstroke) and V, or downstroke ratio (the duration of the downstroke
      divided by the total stroke period) and V. On the other hand, SR decreases
      significantly with increasing wing beat frequency f, SR proportional to f(-0.40).
      The Strouhal number (St=f x amplitude/V), a dimensionless parameter describing
      oscillating flow mechanisms and being a predictor of the unsteadiness of the
      flow, decreases with the speed as St proportional to V(-1.37). Close to the
      theoretical minimum power speed (4-6 m s(-1)) G. soricina operates with a
      Strouhal number in the region 0.17<St<0.22, which is associated with efficient
      lift and thrust production. At slower speeds, 3.4-4 m s(-1), St is 0.25-0.4,
      which is still within the favourable region. But at speeds below 3 m s(-1) St
      becomes higher (0.5<St<0.68), indicating that unsteady effects become important,
      with unfavourable lift and thrust production as a result. Only at these speeds do
      the bats perform the backward flick during the upstroke, which may produce
      thrust. This may serve as a compensation in some bats and birds to increase
      aerodynamic performance.

PMID- 16985206
TI  - Perfusion with cGMP analogue adapts the action potential response of pheromone
      sensitive sensilla trichoidea of the hawkmoth Manduca sexta in a daytime
      dependent manner.
AB  - Pheromone-dependent mate search is under strict circadian control in different
      moth species. But it remains unknown whether daytime-dependent changes in
      pheromone sensitivity already occur at the periphery in male moths. Because
      adapting pheromone stimuli cause rises of cyclic guanosine monophosphate (cGMP)
      in pheromone-sensitive trichoid sensilla of the night-active hawkmoth Manduca
      sexta, we wanted to determine whether cGMP decreases pheromone-sensitivity of
      olfactory receptor neurons in a daytime-dependent manner. Long-term tip
      recordings from trichoid sensilla were performed at the early day (ZT 1-4), when
      many moths are still active, and at the middle of the day (ZT 8-11), when moths
      are resting. A non-adapting pheromone-stimulation protocol combined with
      perfusion of the sensillum lymph with the membrane-permeable cGMP analogue 8bcGMP
      adapted the action potential response but not the sensillar potential. Perfusion
      with 8bcGMP decreased the initial action potential frequency, decreased the
      numbers of action potentials elicited in the first 100 ms of the pheromone
      response and attenuated the reduction of action potential amplitude. Furthermore,
      the decrease in 8bcGMP-dependent action potential frequency was stronger in
      recordings made at ZT 8-11 than at ZT 1-4. In the control recordings during the
      course of the day the pheromone responses became increasingly tonic and less
      phasic. At ZT 8-11 only, this daytime-dependent effect was further enhanced by
      8bcGMP application. Thus we hypothesize that during the moths' resting phase,
      elevated cGMP levels underlie a daytime-dependent decrease in pheromone
      sensitivity and a decline in the temporal resolution of pheromone pulses.

PMID- 16985207
TI  - Proprioceptive encoding of head position in the black soldier fly, Hermetia
      illucens (L.) (Stratiomyidae).
AB  - Because the eyes of insects cannot be moved independently of the head,
      information about head posture is essential for stabilizing the visual world or
      providing information about the direction of gaze. We examined the external
      anatomy and physiological capabilities of a head posture proprioceptor, the
      prosternal organ (PO), located at the base of the neck in the black soldier fly,
      Hermetia illucens (L.) (Family: Stratiomyidae). The PO is sexually isomorphic and
      is composed of two fused plates of about 130 mechanosensory hairs set in
      asymmetrical sockets whose orientation varies across the organ. A multi-joint
      mechanical coupling between the head, neck membrane, and contact sclerites
      deflects the hairs more or less to increase or decrease their level of
      excitation. The PO sensory afferents project to the central nervous system (CNS)
      via a pair of bilateral prosternal nerves (PN) to the fused thoracic ganglia.
      Simultaneous recording of spiking activity in the PN and videotaping of wind
      induced and voluntary head movements around all three axes of head rotation
      reveal that a few PN afferents are active at rest, but activity increases
      tonically in response to head deflections. Activity is significantly modulated by
      change in head angles around the pitch (+/-40 degrees ), yaw (+/-30 degrees ) and
      roll (more than +/-90 degrees ) axes, although the dynamic range of spiking
      activity differs for each axis of rotation. Prosternal nerve afferents are
      bilaterally excited (inhibited) by pitch down (up); excited (inhibited) by head
      yaw toward the ipsilateral (contralateral) side; excited by roll down toward the
      ipsilateral side, but little inhibited by roll toward the opposite side. Although
      bilateral comparison of activity in PN afferents reliably encodes head posture
      around a given rotational axis, from the point of view of the CNS, the problem of
      encoding head posture is ill-posed with three axes of rotation and only two
      streams of afferent information. Furthermore, when the head is rotated around
      more than one axis simultaneously, mechanical interactions in the neck modify the
      responses to postural changes around the three rotational axes, which adds
      further ambiguity to reliable encoding of head posture. The properties of the PO
      in this relatively basal fly species are compared to those of higher flies and
      possible mechanisms of disambiguation are discussed.

PMID- 16985208
TI  - Sagittal spine movements of small therian mammals during asymmetrical gaits.
AB  - Mammalian locomotion is characterized by the use of asymmetrical gaits associated
      with extensive flexions and extensions of the body axis. Although the impact of
      sagittal spine movements on locomotion is well known, little information is
      available on the kinematics of spinal motion. Intervertebral joint movements were
      studied in two metatherian and three eutherian species during the gallop and
      halfbound using high-speed cineradiography. Fast-Fourier transformation was used
      to filter out high frequency digitizing errors and keep the lower frequency
      sinusoid oscillations that characterize the intervertebral angular movements.
      Independent of their regional classification as thoracic or lumbar vertebrae, 7+/
      1 presacral intervertebral joints were involved in sagittal bending movements. In
      only one species, no more than five intervertebral joints contributed to the
      resulting 'pelvic movement'. In general, the trunk region involved in sagittal
      bending during locomotion did not correspond to the traditional subdivisions of
      the vertebral column (e.g. as thoracic and lumbar or pre- and postdiaphragmatic
      region). Therefore, these classifications do not predict the regions involved in
      spinal oscillations during locomotion. Independent of the gait, maximum flexion
      of the spine was observed in the interval between the last third of the swing
      phase and touch-down. This results in a retraction of the pelvis and hindlimbs
      before touch-down and, we hypothesize, enhances the stability of the system.
      Maximum extension occurred during the first third of the swing phase (i.e. after
      lift-off) in all species. In general, the observed timing of dorsoventral
      oscillations of the spine are in accordance with that observed in other mammals
      and with activity data of respiratory and epaxial back muscles. Although no
      strict craniocaudal pattern was observable, the more cranial intervertebral
      joints tend to flex and extend earlier than the more caudal ones. This is in
      accordance with the organization and the activation of the paravertebral
      musculature in mammals. The amplitude of intervertebral joint movements increased
      caudally, reaching its highest values in the presacral joint. The more intense
      sagittal bending movements in the caudal intervertebral joints are reflected by
      the muscle fiber type composition of the back muscles involved. Despite the
      highly similar amplitude of 'pelvic motion', touch-down and lift-off positions of
      the pelvis were clearly different between the species with a long, external tail
      and those with no external tail.

PMID- 16985209
TI  - Cardiorespiratory physiology and swimming energetics of a high-energy-demand
      teleost, the yellowtail kingfish (Seriola lalandi).
AB  - This study utilizes a swimming respirometer to investigate the effects of
      exercise and temperature on cardiorespiratory function of an active teleost, the
      yellowtail kingfish (Seriola lalandi). The standard aerobic metabolic rate (SMR)
      of S. lalandi (mean body mass 2.1 kg) ranges from 1.55 mg min(-1) kg(-1) at 20
      degrees C to 3.31 mg min(-1) kg(-1) at 25 degrees C. This 2.1-fold increase in
      SMR with temperature is associated with a 1.5-fold increase in heart rate from 77
      to 117 beats min(-1), while cardiac stroke volume remains constant at 0.38 ml
      beat(-1) kg(-1) and the difference in oxygen content between arterial and mixed
      venous blood [(Ca(O2)-Cv(O2))] increases marginally from 0.06 to 0.08 mg ml(-1).
      During maximal aerobic exercise (2.3 BL s(-1)) at both temperatures, however,
      increases in cardiac output are limited to about 1.3-fold, and increases in
      oxygen consumption rates (up to 10.93 mg min(-1) kg(-1) at 20 degrees C and 13.32
      mg min(-1) kg(-1) at 25 degrees C) are mediated primarily through augmentation of
      (Ca(O2)-Cv(O2)) to 0.29 mg ml(-1) at 20 degrees C and 0.25 mg ml(-1) at 25
      degrees C. It seems, therefore, that the heart of S. lalandi routinely works
      close to its maximum capacity at a given temperature, and changes in aerobic
      metabolism due to exercise are greatly reliant on high blood oxygen-carrying
      capacity and (Ca(O2)-Cv(O2)). Gross aerobic cost of transport (GCOT) is 0.06 mg
      kg(-1) BL(-1) at 20 degrees C and 0.09 mg kg(-1) BL(-1) at 25 degrees C at the
      optimal swimming velocities (U(opt)) of 1.2 BL s(-1) (opt) and 1.7 BL s(-1),
      respectively. These values are comparable with those reported for salmon and
      tuna, implying that the interspecific diversity in locomotor mode (e.g.
      subcarangiform, carangiform and thunniform) is not concomitant with similar
      diversity in swimming efficiency. A low GCOT is maintained as swimming velocity
      increases above U(opt), which may partly result from energy savings associated
      with the progressive transition from opercular ventilation to ram ventilation.

PMID- 16985210
TI  - Pentoxifylline protects against endotoxin-induced acute renal failure in mice.
AB  - Acute renal failure (ARF) in septic patients drastically increases the mortality
      to 50-80%. Sepsis induces several proinflammatory cytokines including tumor
      necrosis factor-alpha (TNF-alpha), a major pathogenetic factor in septic ARF.
      Pentoxifylline has several functions including downregulation of TNF-alpha and
      endothelia-dependent vascular relaxation. We hypothesized that pentoxifylline may
      afford renal protection during endotoxemia either by downregulating TNF-alpha
      and/or by improving endothelial function. In wild-type mice, pentoxifylline
      protected against the fall in glomerular filtration rate (GFR; 105.2 +/- 6.6 vs.
      50.2 +/- 6.6 microl/min, P < 0.01) at 16 h of LPS administration (2.5 mg/kg ip).
      This renal protective effect of pentoxifylline was associated with an inhibition
      of the rise in serum TNF-alpha (1.00 +/- 0.55 vs. 7.02 +/- 2.40 pg/ml, P < 0.05)
      and serum IL-1beta (31.3 +/- 3.6 vs. 53.3 +/- 5.9 pg/ml, P < 0.01) induced by
      LPS. Pentoxifylline also reversed the LPS-related increase in renal iNOS and ICAM
      1 and rise in serum nitric oxide (NO). Enhanced red blood cell deformability by
      pentoxifylline may have increased shear rate and upregulated eNOS. Studies were
      therefore performed in eNOS knockout mice. The renal protection against
      endotoxemia with pentoxifylline was again observed as assessed by GFR (119.8 +/-
      18.0 vs. 44.5 +/- 16.2 microl/min, P < 0.05) and renal blood flow (0.86 +/- 0.08
      vs. 0.59 +/- 0.05 ml/min, P < 0.05). Renal vascular resistance significantly
      decreased with the pentoxifylline (91.0 +/- 5.8 vs. 178.0 +/- 7.6 mmHg.ml(
      1).min(-1), P < 0.01). Thus pentoxifylline, an FDA-approved drug, protects
      against endotoxemia-related ARF and involves a decrease in serum TNF-alpha, IL
      1beta, and NO as well as a decrease in renal iNOS and ICAM-1.

PMID- 16985211
TI  - Aminoaciduria and altered renal expression of luminal amino acid transporters in
      mice lacking novel gene collectrin.
AB  - Defects in renal proximal tubule transport manifest in a number of human
      diseases. Although variable in clinical presentation, disorders such as Hartnup
      disease, Dent's disease, and Fanconi syndrome are characterized by wasting of
      solutes commonly recovered by the proximal tubule. One common feature of these
      disorders is aminoaciduria. There are distinct classes of amino acid transporters
      located in the apical and basal membranes of the proximal tubules that reabsorb
      >95% of filtered amino acids, yet few details are known about their regulation.
      We present our physiological characterization of a mouse line with targeted
      deletion of the gene collectrin that is highly expressed in the kidney.
      Collectrin-deficient mice display a reduced urinary concentrating capacity due to
      enhanced solute clearance resulting from profound aminoaciduria. The
      aminoaciduria is generalized, characterized by loss of nearly every amino acid,
      and results in marked crystalluria. Furthermore, in the kidney, collectrin
      deficient mice have decreased plasma membrane populations of amino acid
      transporter subtypes B(0)AT1, rBAT, and b(0,+)AT, as well as altered cellular
      distribution of EAAC1. Our data suggest that collectrin is a novel mediator of
      renal amino acid transport and may provide further insight into the pathogenesis
      of a number of human disease correlates.

PMID- 16985212
TI  - Dynamics of aquaporin-2 serine-261 phosphorylation in response to short-term
      vasopressin treatment in collecting duct.
AB  - We recently identified a novel phosphorylation site, serine-261 (pS261), in the
      COOH-terminus of the vasopressin-regulated water channel, aquaporin-2 (AQP2). To
      address whether phosphorylation at this site is regulated by vasopressin, a
      rabbit polyclonal phospho-specific antibody was generated. Dot blot and
      immunoblot analysis demonstrated that this antibody specifically recognizes AQP2
      phosphorylated at pS261, and that phosphorylation of S256 (pS256), a site already
      known to be regulated by vasopressin, does not interfere with antibody
      recognition. Immunohistochemical analysis revealed intense pS261 labeling of
      inner medullary collecting duct (IMCD) from wild-type mice, while sections from
      AQP2 knockout animals showed a general absence of labeling. AQP2 pS261 was
      present in principal cells of all mouse and rat distal tubule segments from the
      connecting tubule to the terminal IMCD. Co-immunolabeling of collecting duct with
      phospho-specific and total AQP2 antibodies revealed that pS261 and pS256 have
      distinct subcellular distributions. Levels of pS256 increased, while the amount
      of pS261 significantly decreased in freshly isolated rat IMCD samples incubated
      with 1 nM [deamino-Cys(1),D-Arg(8)]vasopressin for 30 min. Similarly, based on
      immunohistochemical labeling, the amount of pS261 was reduced in all collecting
      duct segments of Brattleboro rats treated with [deamino-Cys(1),D
      Arg(8)]vasopressin for 2 h. This study reveals a reciprocal change in S256 and
      S261 phosphorylation in response to short-term vasopressin exposure, suggesting
      that these residues may serve distinct roles in regulation of AQP2 subcellular
      distribution and collecting duct water permeability.

PMID- 16985213
TI  - Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in
      klotho mice.
AB  - Recent studies have demonstrated that klotho protein plays a role in
      calcium/phosphate homeostasis. The goal of the present study was to investigate
      the regulation of Na-P(i) cotransporters in klotho mutant (kl/kl) mice. The kl/kl
      mice displayed hyperphosphatemia, high plasma 1,25(OH)(2)D(3) levels, increased
      activity of the renal and intestinal sodium-dependent P(i) cotransporters, and
      increased levels of the type IIa, type IIb, and type IIc transporter proteins
      compared with wild-type mice. Interestingly, transcript levels of the type
      IIa/type IIc transporter mRNA abundance, but not transcripts levels of type IIb
      transporter mRNA, were markedly decreased in kl/kl mice compared with wild-type
      mice. Furthermore, plasma fibroblast growth factor 23 (FGF23) levels were 150
      fold higher in kl/kl mice than in wild-type mice. Feeding of a low-P(i) diet
      induced the expression of klotho protein and decreased plasma FGF23 levels in
      kl/kl mice, whereas colchicine treatment experiments revealed evidence of
      abnormal membrane trafficking of the type IIa transporter in kl/kl mice. Finally,
      feeding of a low-P(i) diet resulted in increased type IIa Na-P(i) cotransporter
      protein in the apical membrane in the wild-type mice, but not in kl/kl mice.
      These results indicate that hyperphosphatemia in klotho mice is due to
      dysregulation of expression and trafficking of the renal type IIa/IIc
      transporters rather than to intestinal P(i) uptake.

PMID- 16985214
TI  - Altered levels of acid, basic, and neutral peptidase activity and expression in
      human clear cell renal cell carcinoma.
AB  - Peptides play important roles in cell regulation and signaling in many tissues
      and are regulated by peptidases, most of which are highly expressed in the
      kidney. Several peptide convertases have a function in different tumor stages,
      and some have been clearly characterized as diagnostic and prognostic markers for
      solid tumors, including renal cancer; however, little is known about their in
      vivo role in kidney tumors. The present study compares the activity of a range of
      peptidases in human tumor samples and nontumor tissue obtained from clear cell
      renal cell carcinoma (CCRCC) patients. To cover the complete spectrum and
      subcellular distribution of peptide-converting activity, acid, neutral, basic,
      and omega activities were selected. CCRCC displays a selective and restricted
      pattern of peptidase activities. Puromycin-sensitive aminopeptidase activity in
      the tumor increases [tumor (t) = 10,775 vs. nontumor (n) = 7,635 units of
      peptidase (UP)/mg protein; P < 0.05], whereas aminopeptidase N decreases (t =
      6,664 vs. n = 33,381 UP/mg protein; P < 0.001). Aminopeptidase B activity of the
      particulate fraction in tumors decreases (t = 2,399 vs. n = 13,536 UP/mg protein;
      P < 0.001) compared with nontumor tissues, and aspartyl-aminopeptidase activity
      decreases significantly in CCRCC (t = 137 vs. n = 223 UP/mg protein; P < 0.05).
      Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A
      activity, and soluble aminopeptidase B activity do not vary in renal cancer. The
      relative expression for the aforementioned peptidases, assayed using quantitative
      RT-PCR, increases in CCRCC for aminopeptidases B (1.5-fold) and A (19-fold),
      aspartyl-aminopeptidase (3.9-fold), puromycin-sensitive aminopeptidase (2.5
      fold), and pyroglutamyl peptidase I (7.6-fold). Only aminopeptidase N expression
      decreases in tumors (1.3-fold). This peptidase activity profile in the neoplastic
      kidney suggests a specific role for the studied convertases and the possible
      involvement of an intracrine renin-angiotensin system in the pathogenesis of
      CCRCC.

PMID- 16985215
TI  - Uric acid inhibits renal proximal tubule cell proliferation via at least two
      signaling pathways involving PKC, MAPK, cPLA2, and NF-kappaB.
AB  - The accumulation of uric acid, an end-product of purine metabolism, is
      responsible for the many deleterious effects observed in gouty arthritis,
      including renal injury. Here, we present evidence that under conditions of
      hyperuricemia (>10(-4) M uric acid) [(3)H]thymidine incorporation into primary
      renal proximal tubule cells (PTCs) is inhibited, and we delineate the signaling
      pathways involved. Elevated uric acid was observed to stimulate MAPK
      phosphorylation. The uric acid induced p38 MAPK phosphorylation was also blocked
      by H-7 (a PKC inhibitor), indicating that p38 MAPK was a downstream target of
      PKC. Evidence that cytoplasmic phospholipase A(2) (cPLA(2)) was involved further
      downstream included 1) the stimulatory effect of uric acid on [(3)H]-labeled
      arachidonic acid (AA) release; 2) the stimulation of AA release in response to
      uric acid was blocked by the PKC inhibitor H-7 as well as by the p38 MAPK
      inhibitor SB 203580; and 3) the uric acid-induced inhibition of [(3)H]thymidine
      incorporation was prevented by SB 203580, as well as by the cPLA(2) inhibitor
      arachidonyl trifluoromethyl ketone, and mepacrine (another PLA(2) inhibitor).
      Evidence of a uric acid-induced activation of NF-kappaB as well as PLA(2) was
      obtained. Moreover the uric acid-induced inhibition of [(3)H]thymidine
      incorporation was also blocked by two NF-kappaB inhibitors, pyrrolidine
      dithiocarbamate and SN 50. However, SN 50 did not block the uric acid induced
      [(3)H]AA release. Thus the inhibition of [(3)H]thymidine incorporation caused by
      uric acid can be explained by two distinct mechanisms, the activation of NF
      kappaB as well as the activation of PLA(2).

PMID- 16985217
TI  - The cover. Harvest.

PMID- 16985216
TI  - Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter.
AB  - Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of
      the renal type IIc Na-P(i) cotransporter gene, suggesting that the type IIc
      transporter plays a prominent role in renal phosphate handling. The goal of the
      present study was to investigate the regulation of the type IIc Na-P(i)
      cotransporter by parathyroid hormone (PTH). Type IIc Na-P(i) cotransporter levels
      were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours
      after administration of PTH, type IIc transporter protein levels were markedly
      decreased in the apical membrane fraction but recovered to baseline levels at 24
      h. Immunohistochemical analyses demonstrated the presence of the type IIc
      transporter in the apical membrane and subapical compartments in the proximal
      tubular cells in TPTX animals. After administration of PTH, the intensity of
      immunoreactive signals in apical and subapical type IIc transporter decreased in
      the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the
      internalization of the type IIc transporter. In addition, leupeptin prevented the
      PTH-mediated degradation of the type IIa transporter in lysosomes but had no
      effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH
      treated TPTX rats, the internalization of the type IIc transporter occurred after
      administration of PTH(1-34) (PKA and PKC activator) or PTH(3-34) (PKC activator).
      Thus the present study demonstrated that PTH is a major hormonal regulator of the
      type IIc Na-P(i) cotransporter in renal proximal tubules.

PMID- 16985218
TI  - A piece of my mind. Mistakes.

PMID- 16985219
TI  - In post-Katrina New Orleans, efforts under way to build better health care.

PMID- 16985220
TI  - CMAJ governance overhauled: firings, resignations, compromised independence
      cited.

PMID- 16985221
TI  - Personality disorder a possibility in "problem" patients, specialists say.

PMID- 16985222
TI  - Hospital performance and acute coronary syndrome outcomes.

PMID- 16985223
TI  - Vaccinia DNA in blood after smallpox vaccination.

PMID- 16985224
TI  - Changing incidence of thyroid cancer.

PMID- 16985225
TI  - Distinguishing organic and functional dyspepsia by history.

PMID- 16985226
TI  - High-sensitivity C-reactive protein and fracture risk in elderly women.

PMID- 16985227
TI  - Trends in fetal and infant survival following preeclampsia.
AB  - CONTEXT: Management of preeclampsia often culminates in induced delivery of a
      very preterm infant. While early termination protects the fetus from an
      intrauterine death, the newborn then faces increased risks associated with
      preterm delivery. This practice has increased in recent decades, but its net
      effect on fetal and infant survival has not been assessed. OBJECTIVE: To assess
      the effect on fetal and infant survival of increased rates of early delivery of
      preeclamptic pregnancies. DESIGN, SETTING, AND PARTICIPANTS: Population-based
      observational longitudinal study using registry data from 804 448 singleton first
      born infants with Norwegian-born mothers and registered in the Medical Birth
      Registry of Norway between 1967 and 2003. MAIN OUTCOME MEASURES: Odds ratio (OR)
      of fetal and early childhood death in relation to preeclampsia. RESULTS: Among
      preeclamptic pregnancies, inductions before 37 weeks increased from 8% in 1967
      1978 to nearly 20% in 1991-2003. During this period, the adjusted OR for
      stillbirth decreased from 4.2 (95% confidence interval [CI], 3.8-4.7) to 1.3 (95%
      CI, 1.1-1.7) for preeclamptic compared with nonpreeclamptic pregnancies. During
      the same period, the OR for neonatal death after preeclamptic pregnancy remained
      relatively stable (1.7 in 1967-1978 vs 2.0 in 1991-2003). Later infant and
      childhood mortality also showed little change. CONCLUSIONS: Fetal survival in
      preeclamptic pregnancies has vastly improved over the past 35 years in Norway,
      presumably because of more aggressive clinical management. However, the relative
      risk of neonatal death following a preeclamptic pregnancy has not changed over
      time.

PMID- 16985228
TI  - Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform
      size, and risk of future cardiovascular events among initially healthy women.
AB  - CONTEXT: Controversy exists as to whether lipoprotein(a), a lipoprotein with
      homology to plasminogen, is a clinically meaningful cardiovascular risk marker in
      women. There is also poor agreement among lipoprotein(a) levels obtained by
      different assays. OBJECTIVE: To determine the association of lipoprotein(a)
      levels, measured with an assay independent of apolipoprotein(a) isoform size,
      with the incidence of future cardiovascular events. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective study of 27,791 initially healthy women in the Women's
      Health Study, enrolled between November 1992 and July 1995 and followed up for 10
      years. Lipoprotein(a) level was measured in blood samples obtained at baseline
      with an assay independent of apolipoprotein(a) isoform size. MAIN OUTCOME
      MEASURE: Hazard ratios (HRs) for first-ever major cardiovascular events (nonfatal
      myocardial infarction, nonfatal cerebrovascular event, coronary
      revascularization, or cardiovascular deaths). RESULTS: During follow-up, there
      were 899 incident cardiovascular events. After adjusting for age, smoking, blood
      pressure, body mass index, total cholesterol, high-density lipoprotein
      cholesterol, diabetes, hormone use, C-reactive protein, and randomization
      treatment groups, women in the highest quintile of lipoprotein(a) (> or =44.0
      mg/dL) were 1.47 times more likely (95% CI, 1.21-1.79; P for trend <.001) to
      develop cardiovascular events than women in the lowest quintile (< or =3.4
      mg/dL). This association, however, was due almost entirely to a threshold effect
      among those with the highest lipoprotein(a) levels. After adjusting for all of
      the variables listed above, the HR associated with lipoprotein(a) levels
      exceeding the 90th percentile (> or =65.5 mg/dL) was 1.66 (95% CI, 1.38-1.99);
      95th percentile (> or =83 mg/dL), 1.87 (95% CI, 1.50-2.34); and 99th percentile
      (> or =130.7 mg/dL), 1.99 (95% CI, 1.32-3.00), with almost no risk gradient at
      lower levels. Associations were strongest among women with low-density
      lipoprotein cholesterol (LDL-C) above the median level. In this subgroup, the
      adjusted HR associated with lipoprotein(a) levels exceeding the 90th percentile
      was 1.81 (95% CI, 1.48-2.23); 95th percentile, 1.93 (95% CI, 1.51-2.48); and 99th
      percentile, 1.93 (95% CI, 1.21-3.05) (P value for interaction with LDL-C = .001).
      CONCLUSIONS: In this cohort of initially healthy women, extremely high levels of
      lipoprotein(a) (> or =90th percentile), measured with an assay independent of
      apolipoprotein(a) isoform size, were associated with increased cardiovascular
      risk, particularly in women with high levels of LDL-C. However, the threshold and
      interaction effects observed do not support routine measurement of lipoprotein(a)
      for cardiovascular stratification in women.

PMID- 16985229
TI  - Long-term fatty fish consumption and renal cell carcinoma incidence in women.
AB  - CONTEXT: The epidemiological evidence that fatty fish consumption may be
      associated with the lower risk of several cancers is not consistent and no
      studies of renal cell carcinoma (RCC) exist. OBJECTIVE: To examine the
      association between fatty and lean fish consumption and risk of RCC in women.
      DESIGN, SETTING, AND PARTICIPANTS: The Swedish Mammography Cohort, a population
      based prospective cohort study of 61,433 women aged 40 to 76 years without
      previous diagnosis of cancer at baseline (March 1, 1987-December 14, 1990).
      Participants filled in a food frequency questionnaire at baseline and in
      September 1997. MAIN OUTCOME MEASURE: Incident renal cell carcinoma. RESULTS:
      During a mean of 15.3 years (940,357 person-years) of follow-up between 1987 and
      2004, 150 incident RCC cases were diagnosed. After adjustment for potential
      confounders, an inverse association of fatty fish consumption with the risk of
      RCC was found (P for trend = .02), but no association was found with lean fish
      consumption. Compared with no consumption, the multivariate rate ratio (RR) was
      0.56 (95% confidence interval [CI], 0.35-0.91) for women eating fatty fish once a
      week or more. Compared with women consistently reporting no fish consumption, the
      multivariate RR was 0.26 (95% CI, 0.10-0.67) for those women reporting consistent
      consumption of fatty fish at baseline and 1997 (based on a subset of 36 664 women
      who filled in the baseline and 1997 questionnaires, with 40 incident RCC cases
      during the 1998-2004 follow-up period). CONCLUSION: Our study suggests that
      consumption of fatty fish may reduce the occurrence of RCC in women.

PMID- 16985230
TI  - Underrepresentation of renal disease in randomized controlled trials of
      cardiovascular disease.
AB  - CONTEXT: Patients with renal disease are at high risk for cardiovascular
      mortality. Determining which interventions best offset this risk remains a health
      priority. OBJECTIVE: To quantify the representation of patients with renal
      disease in randomized controlled trials for interventions proven efficacious for
      cardiovascular disease. DATA SOURCES: We searched MEDLINE for trials published
      from 1985 through 2005 in 11 major medical and subspecialty journals. STUDY
      SELECTION: Randomized controlled trials for chronic congestive heart failure and
      acute myocardial infarction of treatments that are currently listed as class I or
      II recommendations in the current American College of Cardiology/American Heart
      Association guidelines were included. DATA EXTRACTION: Two reviewers
      independently abstracted data on study and patient characteristics, renal
      measurements, outcomes, and prognostic features. DATA SYNTHESIS: A total of 153
      trials were reviewed. Patients with renal disease were reported as excluded in 86
      (56%) trials. Patients with renal disease were more likely to be excluded from
      trials that were multicenter; of moderate enrollment size; North American; that
      tested renin-angiotensin-aldosterone system antagonists and anticoagulants; and
      that tested chronic congestive heart failure. Only 8 (5%) original articles
      reported the proportion of enrolled patients with renal disease, and only 15
      (10%) reported mean baseline renal function. While 81 (53%) trials performed
      subgroup analyses of some baseline characteristic in the original article, only 4
      (3%) subgroup analyses of treatment stratified by renal disease were performed.
      CONCLUSION: Major cardiovascular disease trials frequently exclude patients with
      renal disease and do not provide adequate information on the renal function of
      enrollees or the effect of interventions on patients with renal disease.

PMID- 16985231
TI  - Spiritual issues in the care of dying patients: ". . . it's okay between me and
      god".
AB  - Spiritual issues arise frequently in the care of dying patients, yet health care
      professionals may not recognize them, may not believe they have a duty to address
      these issues, and may not understand how best to respond to their patients'
      spiritual needs. The case of a patient with a strong religious belief in a
      miraculous cure of metastatic pancreatic cancer is used to explore how better
      understanding of this belief and more explicitly spiritual conversation with the
      patient by his treating team might have provided opportunities for an improved
      plan of care. This article distinguishes spirituality from religion; describes
      the salient spiritual needs of patients at the end of life as encompassing
      questions of meaning, value, and relationship; delineates the role physicians
      ought to play in ascertaining and responding to those needs; and discusses the
      particular issue of miracles, arguing that expectations of miraculous cure ought
      not preclude referral to hospice care.

PMID- 16985232
TI  - Sudden traumatic death in children: "we did everything but your child didn't
      survive".

PMID- 16985233
TI  - Federal health policy response to Hurricane Katrina: what it was and what it
      could have been.

PMID- 16985234
TI  - Terminal withdrawal of life-sustaining supplemental oxygen.

PMID- 16985235
TI  - Apology in medical practice: an emerging clinical skill.

PMID- 16985236
TI  - JAMA patient page. Palliative care.

PMID- 16985237
TI  - Cross-linking transglutaminases with G protein-coupled receptor signaling.
AB  - Transglutaminases are a family of calcium- and thiol-dependent acyl transferases
      that catalyze the formation of an amide bond between the gamma-carboxamide groups
      of peptide-bound glutamine residues and the primary amino groups in various
      compounds, including the epsilon-amino group of lysines in certain proteins. As a
      result, these enzymes effect posttranslational modification of proteins by amine
      incorporation, or stabilization of protein assemblies by their cross-linking;
      such actions profoundly influence critical biological processes such as blood
      clotting and protection from infection and dehydration by establishing the
      barrier function of skin. In addition, transglutaminases have other more diverse
      actions, including involvement in signaling by the superfamily of heterotrimeric
      guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) in one
      of three ways: (i) through actions as guanosine triphosphate-binding proteins
      that activate intracellular effectors, such as phospholipase C; (ii) by cross
      linking GPCR monomers to enhance signaling as a result of covalent dimer
      formation; or (iii) by interacting with an apparent growth inhibitory orphan
      GPCR, GPR56, to limit metastatic spread of melanoma cells. The implications of
      these receptor-coupled actions of transglutaminases are discussed.

PMID- 16985238
TI  - Simultaneous optical measurements of cytosolic Ca2+ and cAMP in single cells.
AB  - Understanding the temporal and spatial integration of the Ca2+ and adenosine
      3',5'-monophosphate (cAMP) signaling pathways requires concurrent measurements of
      both second messengers. Here, we describe an optical technique to simultaneously
      image cAMP and Ca2+ concentration gradients in MIN6 mouse insulinoma cells using
      Epac1-camps, a Forster (or fluorescence) resonance energy transfer (FRET)-based
      cAMP biosensor, and Fura-2, a fluorescent indicator of Ca2+. This real-time
      imaging method allows investigation of the dynamic organization and integration
      of multiple levels of signal processing in single living cells.

PMID- 16985239
TI  - Aromatase inhibitors for the treatment of breast cancer: is tamoxifen of
      historical interest only?

PMID- 16985240
TI  - Idiotype vaccination in follicular lymphoma: knocking on the doorway to cure.

PMID- 16985241
TI  - John Niederhuber: thinking like a director.

PMID- 16985242
TI  - Patient group seeks overhaul of FDA clinical trial system in court.

PMID- 16985243
TI  - The race for ancestral genetics in clinical trials.

PMID- 16985244
TI  - Sometimes size doesn't matter: reevaluating RECIST and tumor response rate
      endpoints.

PMID- 16985245
TI  - Stat bite: Cigarette use among high school students, 1991-2005.

PMID- 16985246
TI  - Addressing the soy and breast cancer relationship: review, commentary, and
      workshop proceedings.
AB  - The impact of soyfood intake on breast cancer risk has been investigated
      extensively. Much of this focus can be attributed to the soybean being a dietary
      source that is uniquely rich in isoflavones. The chemical structure of
      isoflavones is similar to that of estrogen, and isoflavones bind to both estrogen
      receptors (ER alpha and ER beta) (although they preferentially bind to and
      activate ER beta) and exert estrogen-like effects under some experimental
      conditions. Isoflavones also possess nonhormonal properties that are associated
      with the inhibition of cancer cell growth. Thus, there are several possible
      mechanisms by which soy may reduce the risk of breast cancer. However, the role
      of isoflavones in breast cancer has become controversial because, in contrast to
      the possible beneficial effects, some data from in vitro and animal studies
      suggest that isoflavones, especially genistein, the aglycone of the main soybean
      isoflavone genistin, may stimulate the growth of estrogen-sensitive tumors.
      Limited human data directly address the tumor-promoting effects of isoflavones
      and soy. Because the use of soyfoods and isoflavone supplements is increasing, it
      is important from a public health perspective to understand the impact of these
      products on breast cancer risk in women at high risk of the disease and on the
      survival of breast cancer patients. To this end, a workshop was held in November
      2005 to review the existing literature and to make research recommendations. This
      paper summarizes the workshop findings and recommendations. The primary research
      recommendation is that the impact of isoflavones on breast tissue needs to be
      evaluated at the cellular level in women at high risk for breast cancer.

PMID- 16985247
TI  - Survival with aromatase inhibitors and inactivators versus standard hormonal
      therapy in advanced breast cancer: meta-analysis.
AB  - BACKGROUND: Aromatase inhibitors and inactivators have been extensively tested in
      patients with advanced breast cancer, but it is unclear whether they offer any
      survival benefits compared with standard hormonal treatment with tamoxifen or
      progestagens. We performed a meta-analysis of randomized controlled trials that
      compared several generations of aromatase inhibitors and inactivators with
      standard hormonal treatment in patients with advanced breast cancer. METHODS: The
      endpoint that we assessed was survival. Trials were located through searches of
      PubMed and Cochrane Library (last update March 2006). Relative hazards (RHs) were
      summarized across trials through fixed- and random-effects analyses, and
      heterogeneity was assessed with the Q and I2 statistics. All statistical tests
      were two-sided. RESULTS: Twenty-five different comparisons, with a total of 8504
      patients, were included in the meta-analysis. We found statistically significant
      survival benefits with third-generation aromatase inhibitors and inactivators
      (vorozole, letrozole, examestane, and anastrazole) (RH = 0.87, 95% confidence
      interval [CI] = 0.82 to 0.93; P<.001) but not with first-generation
      (aminoglutethimide) or second-generation (formestane and fadrozole) agents. The
      difference in the summary effects between these two groups of trials was
      statistically significant (P = .04). The survival benefit with third-generation
      agents in first-line trials, in which these agents were compared with tamoxifen
      (11% RH reduction, 95% CI = 1% to 19%; P = .03), was identical to their benefit
      in second- and subsequent-line trials in which these agents were compared with
      other treatments (14% RH reduction, 95% CI = 6% to 21%; P<.001). CONCLUSIONS:
      Inhibition of the aromatase system, in particular with third-generation aromatase
      inhibitors and inactivators, appears to be associated with statistically
      significant improved survival of patients with advanced breast cancer compared
      with standard hormonal treatments.

PMID- 16985248
TI  - Clinical benefit associated with idiotypic vaccination in patients with
      follicular lymphoma.
AB  - BACKGROUND: Follicular lymphoma is considered incurable, although
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy
      can induce sequential remissions. A patient's second complete response is
      typically shorter than that patient's first complete response. Idiotype vaccines
      can elicit specific immune responses and molecular remissions in patients with
      follicular lymphoma. However, a clinical benefit has never been formally proven.
      METHODS: Thirty-three consecutive follicular lymphoma patients in first relapse
      received six monthly cycles of CHOP-like chemotherapy. Patients who achieved a
      second complete response were vaccinated periodically for more than 2 years with
      autologous lymphoma-derived idiotype protein vaccine. Specific humoral and
      cellular responses were assessed, and patients were followed for disease
      recurrence. Statistical tests were two-sided. RESULTS: Idiotype vaccine could be
      produced for 25 patients who had a second complete response. In 20 patients
      (80%), a humoral (13/20) and/or a cellular (18/20) idiotype-specific response was
      detected. The median duration of the second complete response has not been
      reached, but it exceeds 33 months (range = 20+ to 51+ months). None of the 20
      responders relapsed while undergoing active vaccination. All responders with
      enough follow-up for the comparison to be made experienced a second complete
      response that was statistically significantly (P<.0001) longer than both their
      first complete response (18 of 18 patients) and than the median duration of a
      CHOP-induced second complete response, i.e., 13 months (20 of 20 patients). The
      five nonresponders all had a second complete response that was shorter (median =
      10 months; range = 8-13 months) than their first complete response (median = 17
      months; range = 10-39 months). CONCLUSIONS: Idiotypic vaccination induced a
      specific immune response in the majority of patients with follicular lymphoma.
      Specific immune response was associated with a dramatic and highly statistically
      significant increase in disease-free survival. This is the first formal
      demonstration of clinical benefit associated with the use of a human cancer
      vaccine.

PMID- 16985249
TI  - Effectiveness of radiation therapy in older women with ductal carcinoma in situ.
AB  - BACKGROUND: For women with ductal carcinoma in situ (DCIS), radiation therapy
      after conservative surgery lowers the risk of recurrence. However, emerging
      evidence suggests that radiation therapy confers only a marginal absolute benefit
      for older women with DCIS. In a cohort of older women with DCIS, we sought to
      determine whether radiation therapy was associated with a clinically significant
      benefit. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)
      Medicare database from January 1, 1992, through December 31, 1999, we identified
      3409 women aged 66 years or older treated with conservative surgery for DCIS. A
      proportional hazards model tested whether radiation therapy was associated with a
      lower risk of a combined outcome, defined as a subsequent ipsilateral in situ or
      invasive breast cancer reported by SEER and/or a subsequent mastectomy reported
      by Medicare claims. The 5-year event risk was determined for patients without and
      with high-risk features, which were defined as at least one of the following: age
      66-69 years, tumor larger than 2.5 cm, comedo histology, and/or high grade. All
      statistical tests were two-sided. RESULTS: Radiation therapy was associated with
      a lower risk for each component of the combined outcome (hazard ratio = 0.32, 95%
      confidence interval [CI] = 0.24 to 0.44). For high-risk patients, the 5-year
      event risk was 13.6% without radiation therapy versus 3.8% with radiation therapy
      (difference = 9.8%, 95% CI = 6.5 to 13.2; P<.001). For low-risk patients, the 5
      year event risk was 8.2% without radiation therapy versus 1.0% with radiation
      therapy (difference = 7.2%, 95% CI = 3.6 to 10.9; P<.001). Among healthy women
      aged 66-79 years, the number needed to treat with radiation therapy to prevent
      one event in 5 years was 11 for high-risk patients and 15-16 for low-risk
      patients. CONCLUSION: For older women with DCIS, radiation therapy appears to
      confer a substantial benefit that remains meaningful even among low-risk
      patients.

PMID- 16985250
TI  - Estrogen sulfation genes, hormone replacement therapy, and endometrial cancer
      risk.
AB  - BACKGROUND: Unopposed estrogen replacement therapy is associated with increased
      risk of endometrial cancer. To investigate the mechanism of this association, we
      evaluated whether risk of endometrial cancer was associated with the genotypes
      involved in steroid hormone metabolism and the duration of exogenous hormone use.
      METHODS: A population-based case-control study in nine counties of the
      Philadelphia metropolitan area was undertaken with 502 case patients with
      endometrial cancer and 1326 age- and race-matched control subjects. Data
      regarding exogenous hormone use were obtained by interview, and genotypes of the
      genes COMT, CYP1A1, CYP1A2, CYP1B1, CYP3A4, PGR, SULT1A1, SULT1E1, and UGT1A1
      were obtained by polymerase chain reaction techniques. Conditional logistic
      regression was used to examine the relationship among genotype, hormone use, and
      endometrial cancer risk. RESULTS: Associations were observed between the risk of
      endometrial cancer and genotypes of the following steroid hormone metabolism
      genes: CYP1A1*2C (adjusted odds ratio [OR] = 1.68, 95% confidence interval [CI] =
      1.08 to 2.61); SULT1A1*3 (adjusted OR = 0.51, 95% CI = 0.29 to 0.92); and the G -
      > A variant in the promoter of SULT1E1 at position -64 (adjusted OR = 1.45, 95%
      CI = 1.06 to 1.99). We observed a statistically significant interaction between
      estrogen replacement therapy use and SULT1A1*2 genotype: the SULT1A1*2 allele and
      long-term use of estrogen replacement therapy were associated with statistically
      significantly higher risk of endometrial cancer (adjusted OR = 3.85, 95% CI =
      1.48 to 10.00) than that of the SULT1A1*2 allele and no estrogen replacement
      therapy use. CONCLUSIONS: Among women with long-term use of estrogen replacement
      therapy or combined hormone replacement therapy, the risk of endometrial cancer
      may be associated with functionally relevant genotypes that regulate steroid
      hormone sulfation.

PMID- 16985251
TI  - Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case
      control study in Scandinavia.
AB  - BACKGROUND: Personal history of autoimmune diseases is consistently associated
      with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data
      on risk of Hodgkin lymphoma following autoimmune diseases and almost no data
      addressing whether there is a familial association between the conditions.
      METHODS: Using population-based linked registry data from Sweden and Denmark, 32
      separate autoimmune and related conditions were identified from hospital
      diagnoses in 7476 case subjects with Hodgkin lymphoma, 18,573 matched control
      subjects, and more than 86,000 first-degree relatives of case and control
      subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as
      measures of relative risks for each condition using logistic regression and also
      applied multivariable hierarchical regression models. All P values are two-sided.
      RESULTS: We found statistically significantly increased risks of Hodgkin lymphoma
      associated with personal histories of several autoimmune conditions, including
      rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus
      erythematosus (OR = 5.8, 95% CI = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI =
      5.4 to 36.8), and immune thrombocytopenic purpura (OR = infinity, P = .002). A
      statistically significant increase in risk of Hodgkin lymphoma was associated
      with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and
      ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). CONCLUSIONS: Personal or
      family history of certain autoimmune conditions was strongly associated with
      increased risk of Hodgkin lymphoma. The association between both personal and
      family histories of sarcoidosis and a statistically significantly increased risk
      of Hodgkin lymphoma suggests shared susceptibility for these conditions.

PMID- 16985252
TI  - Rising incidence of small renal masses: a need to reassess treatment effect.
AB  - The incidence of kidney cancer has been rising over the last two decades,
      especially in cases where the disease is localized. Although rates of renal
      surgery parallel this trend, mortality rates have continued to rise. To
      investigate the basis of this "treatment disconnect" (i.e., increased rates of
      treatment accompanied by increased mortality rates), we analyzed patient data
      from nine registries of the National Cancer Institute's Surveillance,
      Epidemiology, and End Results Program. We assembled a cohort of 34,503 kidney
      cancer patients and derived incidence, treatment, and mortality trends for kidney
      cancer, overall and as a function of tumor size. From 1983 to 2002, the overall
      age-adjusted incidence rate for kidney cancer rose from 7.1 to 10.8 cases per
      100,000 US population; tumors < or = 4 cm in size accounted for most of the
      increase. Adjusted rates of renal surgery increased concurrently, most notably
      for tumors < or = 4 cm (0.9-3.6 surgeries per 100,000 US population). However,
      among kidney cancer patients, all-cause mortality per 100,000 US population
      increased from 1.5 deaths in 1983 to 6.5 deaths in 2002, with the greatest
      absolute increase noted for patients with lesions > 7 cm. Our results demonstrate
      that the rising incidence of kidney cancer is largely attributable to an increase
      in small renal masses that are presumably curable. The fact that increased
      detection and treatment of small tumors is not reducing mortality argues for a
      reassessment of the current treatment paradigm.

PMID- 16985254
TI  - The LDL receptor is not necessary for acute adrenal steroidogenesis in mouse
      adrenocortical cells.
AB  - Steroid hormones are synthesized using cholesterol as precursor. To determine the
      functional importance of the low density lipoprotein (LDL) receptor and hormone
      sensitive lipase (HSL) in adrenal steroidogenesis, adrenal cells were isolated
      from control, HSL(-/-), LDLR(-/-), and double LDLR/HSL(-/-) mice. The endocytic
      and selective uptake of apolipoprotein E-free human high density lipoprotein
      (HDL)-derived cholesteryl esters did not differ among the mice, with selective
      uptake accounting for >97% of uptake. In contrast, endocytic uptake of either
      human LDL- or rat HDL-derived cholesteryl esters was reduced 80-85% in LDLR(-/-)
      and double-LDLR/HSL(-/-) mice. There were no differences in the selective uptake
      of either human LDL- or rat HDL-derived cholesteryl esters among the mice.
      Maximum corticosterone production induced by ACTH or dibutyryl cyclic AMP and
      lipoproteins was not altered in LDLR(-/-) mice but was reduced 80-90% in HSL(-/-)
      mice. Maximum corticosterone production was identical in HSL(-/-) and double
      LDLR/HSL(-/-) mice. These findings suggest that, although the LDL receptor is
      responsible for endocytic delivery of cholesteryl esters from LDL and rat HDL to
      mouse adrenal cells, it appears to play a negligible role in the delivery of
      cholesterol for acute adrenal steroidogenesis in the mouse. In contrast, HSL
      occupies a vital role in adrenal steroidogenesis because of its link to
      utilization of selectively delivered cholesteryl esters from lipoproteins.

PMID- 16985253
TI  - Measuring disease-free survival and cancer relapse using Medicare claims from
      CALGB breast cancer trial participants (companion to 9344).
AB  - To determine the accuracy with which Medicare claims data measure disease-free
      survival in elderly Medicare beneficiaries with cancer, we performed a criterion
      validation study. We merged gold-standard clinical trial data of 45 elderly
      patients with node-positive breast cancer who were treated on the Cancer and
      Leukemia Group B (CALGB) adjuvant breast trial 9344 with Centers for Medicare and
      Medicaid Services (CMS) data files and compared the results of a CMS-based
      algorithm with the CALGB disease-free survival information to determine
      sensitivity and specificity. For 5-year disease-free survival, the sensitivity of
      the CMS-based algorithm was 100% (95% confidence interval [CI] = 81% to 100%),
      the specificity was 97% (95% CI = 83% to 100%), and the area under the receiver
      operator curve was 98[corrected]% (95% CI = 95[corrected]% to 100%). For 2-year
      disease-free survival, the test characteristics were less favorable: sensitivity
      was 83% (95% CI = 36% to 100%), specificity was 95% (95% CI = 83% to 100%), and
      area under the receiver operator curve was 89[corrected]% (95% CI =
      72[corrected]% to 100%).

PMID- 16985255
TI  - Degradation of STAT5 proteins in 3T3-L1 adipocytes is induced by TNF-{alpha} and
      cycloheximide in a manner independent of STAT5A activation.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that has
      been implicated as a causative factor in obesity-linked insulin resistance. It is
      commonly accepted that macrophage-derived TNF-alpha acts in a paracrine manner on
      adjacent adipocytes to inhibit the expression of various adipocyte genes and to
      attenuate insulin signaling. Several studies have revealed that signal transducer
      and activator of transcription (STAT)5 proteins are modulated during adipogenesis
      and can modulate the transcription of some adipocyte genes. In this study, we
      demonstrate that TNF-alpha treatment, in the presence of cycloheximide, also
      results in the rapid turnover of STAT5A and STAT5B in a process that is
      independent of STAT5 activation by tyrosine phosphorylation. In addition, STAT5B
      is more labile than STAT5A under these conditions, suggesting that the COOH
      terminus of STAT5 may be involved in the turnover of each protein. Initial
      characterization of the TNF-alpha and cycloheximide-mediated degradation of STAT5
      indicates that inhibition of the proteasome stabilizes both forms of STAT5 in the
      presence of TNF-alpha. In addition, the use of an NF-kappaB inhibitor results in
      the stabilization of STAT5A in the presence of TNF-alpha and cycloheximide,
      indicating that the degradation of STAT5 proteins under these conditions may
      involve the NF-kappaB pathway. STAT5 proteins are abundantly expressed in mature
      adipocytes and are normally extremely stable proteins under a wide range of
      conditions. However, our results demonstrate that the potentiation of TNF-alpha
      mediated signaling in the presence of cyclohexmide is associated with a
      significant increase in the degradation of STAT5 proteins in 3T3-L1 adipocytes.

PMID- 16985256
TI  - Effects of 3-phosphoglycerate and other metabolites on the activation of AMP
      activated protein kinase by LKB1-STRAD-MO25.
AB  - Skeletal muscle contraction results in the phosphorylation and activation of the
      AMP-activated protein kinase (AMPK) by an upstream kinase (AMPKK). The LKB1-STE
      related adaptor (STRAD)-mouse protein 25 (MO25) complex is the major AMPKK in
      skeletal muscle; however, LKB1-STRAD-MO25 activity is not increased by muscle
      contraction. This relationship suggests that phosphorylation of AMPK by LKB1
      STRAD-MO25 during skeletal muscle contraction may be regulated by allosteric
      mechanisms. In this study, we tested an array of metabolites including, glucose 6
      phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, 3-phosphoglycerate (3
      PG), glucose 1-phosphate, glucose 1,6-bisphosphate, ADP, carnitine,
      acetylcarnitine, IMP, inosine, and ammonia for allosteric regulation. ADP
      inhibited both AMPK and LKB1-STRAD-MO25 actions, but probably is not important
      physiologically because of the low free ADP inside the muscle fiber. We found
      that 3-PG stimulated LKB1-STRAD-MO25 activity and allowed for increased AMPK
      phosphorylation. 3-PG did not stimulate LKB1-STRAD-MO25 activity toward the
      peptide substrate LKB1tide. These results have identified 3-PG as an AMPK
      specific regulator of AMPK phosphorylation and activation by LKB1-STRAD-MO25.

PMID- 16985257
TI  - The dominant negative thyroid hormone receptor beta-mutant {Delta}337T alters
      PPAR{alpha} signaling in heart.
AB  - PPARalpha and TR independently regulate cardiac metabolism. Although ligands for
      both these receptors are currently under evaluation for treatment of congestive
      heart failure, their interactions or signaling cooperation have not been
      investigated in heart. We tested the hypothesis that cardiac TRs interact with
      PPARalpha regulation of target genes and used mice exhibiting a cardioselective
      Delta337T TRbeta1 mutation (MUT) to reveal cross-talk between these nuclear
      receptors. This dominant negative transgene potently inhibits DNA binding for
      both wild-type (WT) TRalpha and TRbeta. We used UCP3 and MTE-1 as principal
      reporters and analyzed gene expression from hearts of transgenic (MUT) and
      nontransgenic (WT) littermates 6 h after receiving either specific PPARalpha
      ligand (WY-14643) or vehicle. Interactions were determined through qRT-PCR
      analyses, and the extent of these interactions across multiple genes was
      determined using expression arrays. In the basal state, we detected no
      differences between groups for protein content for UCP3, PPARalpha, TRalpha2,
      RXRbeta, or PGC-1alpha. However, protein content for TRalpha1 and the PPARalpha
      heterodimeric partner RXRalpha was diminished in MUT, whereas PPARbeta increased.
      We demonstrated cross-talk between PPAR and TR for multiple genes, including the
      reporters UCP3 and MTE1. WY-14643 induced a twofold increase in UCP3 gene
      expression that was totally abrogated in MUT. We demonstrated variable cross-talk
      patterns, indicating that multiple mechanisms operate according to individual
      target genes. The non-ligand-binding TRbeta1 mutation alters expression for
      multiple nuclear receptors, providing a novel mechanism for interaction that has
      not been previously demonstrated. These results indicate that therapeutic
      response to PPARalpha ligands may be determined by thyroid hormone state and TR
      function.

PMID- 16985258
TI  - Are blood flow and lipolysis in subcutaneous adipose tissue influenced by
      contractions in adjacent muscles in humans?
AB  - Aerobic exercise increases whole body adipose tissue lipolysis, but is lipolysis
      higher in subcutaneous adipose tissue (SCAT) adjacent to contracting muscles than
      in SCAT adjacent to resting muscles? Ten healthy, overnight-fasted males
      performed one-legged knee extension exercise at 25% of maximal workload (W(max))
      for 30 min followed by exercise at 55% W(max) for 120 min with the other leg and
      finally exercised at 85% W(max) for 30 min with the first leg. Subjects rested
      for 30 min between exercise periods. Femoral SCAT blood flow was estimated from
      washout of (133)Xe, and lipolysis was calculated from femoral SCAT interstitial
      and arterial glycerol concentrations and blood flow. In general, blood flow and
      lipolysis were higher in femoral SCAT adjacent to contracting than adjacent to
      resting muscle (time 15-30 min; blood flow: 25% W(max) 6.6 +/- 1.0 vs. 3.9 +/-
      0.8 ml x 100 g(-1) x min(-1), P < 0.05; 55% W(max) 7.3 +/- 0.6 vs. 5.0 +/- 0.6 ml
      x 100 g(-1) x min(-1), P < 0.05; 85% W(max) 6.6 +/- 1.3 vs. 5.9 +/- 0.7 ml x 100
      g(-1) x min(-1), P > 0.05; lipolysis: 25% W(max) 102 +/- 19 vs. 55 +/- 14 nmol x
      100 g(-1) x min(-1), P = 0.06; 55% W(max) 86 +/- 11 vs. 50 +/- 20 nmol x 100 g(
      1) x min(-1), P > 0.05; 85% W(max) 88 +/- 31 vs. -9 +/- 25 nmol x 100 g(-1) x
      min(-1), P < 0.05). In conclusion, blood flow and lipolysis are generally higher
      in SCAT adjacent to contracting than adjacent to resting muscle irrespective of
      exercise intensity. Thus specific exercises can induce "spot lipolysis" in
      adipose tissue.

PMID- 16985259
TI  - Identification of depot-specific human fat cell progenitors through distinct
      expression profiles and developmental gene patterns.
AB  - Anatomically separate fat depots differ in size, function, and contribution to
      pathological states, such as the metabolic syndrome. We isolated preadipocytes
      from different human fat depots to determine whether the basis for this variation
      is partly attributable to differences in inherent properties of fat cell
      progenitors. We found that genome-wide expression profiles of primary
      preadipocytes cultured in parallel from abdominal subcutaneous, mesenteric, and
      omental fat depots were distinct. Interestingly, visceral fat was not
      homogeneous. Preadipocytes from one of the two main visceral depots, mesenteric
      fat, had an expression profile closer to that of subcutaneous than omental
      preadipocytes, the other main visceral depot. Expression of genes that regulate
      early development, including homeotic genes, differed extensively among
      undifferentiated preadipocytes isolated from different fat depots. These profiles
      were confirmed by real-time PCR analysis of preadipocytes from additional lean
      and obese male and female subjects. We made preadipocyte strains from single
      abdominal subcutaneous and omental preadipocytes by expressing telomerase. Depot
      specific developmental gene expression profiles persisted for 40 population
      doublings in these strains. Thus, human fat cell progenitors from different
      regions are effectively distinct, consistent with different fat depots being
      separate mini-organs.

PMID- 16985260
TI  - Regulation of IGF-I receptor signaling in diabetic cardiac muscle: dysregulation
      of cytosolic and mitochondria HSP60.
AB  - Insulin deficiency downregulates HSP60 and IGF-I receptor signaling and disrupts
      intracellular signaling homeostasis in diabetic cardiac muscle. Our previous
      studies had shown that IGF-I receptor signaling can be modulated by the abundance
      of HSP60. Since HSP60 localizes to the cytoplasmic compartment and mitochondria,
      this study was carried out to determine the distribution of cytosolic and
      mitochondria HSP60 in diabetic myocardium and to explore whether cytosolic HSP60
      can modulate IGF-I receptor signaling in cardiac muscle cells. In streptozotocin
      induced diabetes, both the cytosolic and mitochondrial fractions of HSP60 were
      decreased in the myocardium. Incubating primary cardiomyocytes with insulin leads
      to increased abundance of HSP60 in the cytosolic and mitochondria compartments.
      To determine whether cytosolic HSP60 can modulate IGF-I receptor signaling, we
      used rhodamine 6G to deplete functional mitochondria in cardiomyocytes. In the
      mitochondria-depleted cells, overexpression of HSP60 with adenoviral vector
      increased the abundance of IGF-I receptor, enhanced IGF-I-activated receptor
      phosphorylation, and augmented IGF-I activation of Akt and ERK. Thus
      overexpressing HSP60 in the cytosolic compartment enhanced IGF-I receptor
      signaling through upregulation of IGF-I receptor protein. However, IGF-I receptor
      signaling was significantly reduced in the mitochondria-depleted cells, which
      suggested that maintaining normal IGF-I receptor signaling in cardiomyocytes
      required functioning mitochondria. The effect of cytosolic HSP60 involved
      suppression of ubiquitin conjugation to IGF-I receptor in cardiomyocytes. These
      data suggest two different mechanisms that can regulate IGF-I signaling, one via
      cytosolic HSP60 suppression of IGF-I receptor ubiquitination and the other via
      mitochondria modulation. These findings provide new insight into the regulation
      of IGF-I signaling in diabetic cardiomyopathy.

PMID- 16985261
TI  - Regulation of HOXA10 expression by phytoestrogens.
AB  - HOXA10 is necessary for normal development of the Mullerian duct, and continued
      adult expression in the uterus is necessary for female fertility. HOXA10
      expression is altered by diethylstilbestrol, leading to uterine anomalies. Other
      endocrine disruptors may potentially lead to reproductive anomalies or
      dysfunction by altering HOXA10 expression. Here we investigated the effect of
      isoflavones on HOXA10 expression after in utero or adult exposure in the mouse.
      Genistein, but not diadzein, regulated HOXA10 mRNA and protein expression in the
      adult mouse uterus. In contrast, in utero genistein or diadzein exposure had no
      lasting effect on HOXA10 expression in the exposed offspring. Reporter gene
      expression driven by the HOXA10 estrogen response element was increased in a dose
      responsive manner by genistein, but not daidzein. Neither estrogen receptor-alpha
      nor estrogen receptor-beta binding to the HOXA10 estrogen response element was
      affected by genistein or daidzein. In utero exposure to isoflavones is unlikely
      to result in HOXA10-mediated developmental anomalies. Adult genistein exposure
      alters uterine HOXA10 expression, a potential mechanism by which this agent
      affects fertility.

PMID- 16985262
TI  - PPAR{alpha} mediates the hypolipidemic action of fibrates by antagonizing FoxO1.
AB  - High-fructose consumption is associated with insulin resistance and diabetic
      dyslipidemia, but the underlying mechanism is unclear. We show in hamsters that
      high-fructose feeding stimulated forkhead box O1 (FoxO1) production and promoted
      its nuclear redistribution in liver, correlating with augmented apolipoprotein C
      III (apoC-III) production and impaired triglyceride metabolism. High-fructose
      feeding upregulated peroxisome proliferator-activated receptor-gamma coactivator
      1beta and sterol regulatory element binding protein-1c expression, accounting for
      increased fat infiltration in liver. High-fructose-fed hamsters developed
      hypertriglyceridemia, accompanied by hyperinsulinemia and glucose intolerance.
      These metabolic aberrations were reversible by fenofibrate, a commonly used anti
      hypertriglyceridemia agent that is known to bind and activate peroxisome
      proliferator-activated receptor-alpha (PPARalpha). PPARalpha physically
      interacted with, but functionally antagonized, FoxO1 in hepatic apoC-III
      expression. These data underscore the importance of FoxO1 deregulation in the
      pathogenesis of hypertriglyceridemia in high-fructose-fed hamsters.
      Counterregulation of hepatic FoxO1 activity by PPARalpha constitutes an important
      mechanism by which fibrates act to curb apoC-III overproduction and ameliorate
      hypertriglyceridemia.

PMID- 16985263
TI  - Exercise and CaMK activation both increase the binding of MEF2A to the Glut4
      promoter in skeletal muscle in vivo.
AB  - In vitro binding assays have indicated that the exercise-induced increase in
      muscle GLUT4 is preceded by increased binding of myocyte enhancer factor 2A
      (MEF2A) to its cis-element on the Glut4 promoter. Because in vivo binding
      conditions are often not adequately recreated in vitro, we measured the amount of
      MEF2A that was bound to the Glut4 promoter in rat triceps after an acute swimming
      exercise in vivo, using chromatin immunoprecipitation (ChIP) assays. Bound MEF2A
      was undetectable in nonexercised controls or at 24 h postexercise but was
      significantly elevated approximately 6 h postexercise. Interestingly, the
      increase in bound MEF2A was preceded by an increase in autonomous activity of
      calcium/calmodulin-dependent protein kinase (CaMK) II in the same muscle. To
      determine if CaMK signaling mediates MEF2A/DNA associations in vivo, we performed
      ChIP assays on C(2)C(12) myotubes expressing constitutively active (CA) or
      dominant negative (DN) CaMK IV proteins. We found that approximately 75% more
      MEF2A was bound to the Glut4 promoter in CA compared with DN CaMK IV-expressing
      cells. GLUT4 protein increased approximately 70% 24 h after exercise but was
      unchanged by overexpression of CA CaMK IV in myotubes. These results confirm that
      exercise increases the binding of MEF2A to the Glut4 promoter in vivo and
      provides evidence that CaMK signaling is involved in this interaction.

PMID- 16985264
TI  - Endothelin-1 decreases CD36 protein expression in vascular smooth muscle cells.
AB  - Recent studies have shown that CD36 plays important roles as a major scavenger
      receptor for oxidized low-density lipoproteins and as a crucial transporter for
      long-chain fatty acids. CD36 deficiency might be associated with insulin
      resistance and abnormal dynamics of long-chain fatty acids. Endothelin-1 (ET-1),
      which is synthesized and secreted by vascular endothelial cells, is the most
      potent endogenous vasoconstrictor known and also stimulates the proliferation of
      vascular smooth muscle cells (VSMCs) and thus is believed to play an important
      role in the development of various circulatory disorders, including hypertension
      and atherosclerosis. The aim of the present study was to investigate the
      regulatory effect of ET-1 on CD36 expression in cultured VSMCs. VSMCs were
      treated for different times (0-24 h) with a fixed concentration (100 nM) of ET-1
      or with different concentrations (0-100 nM) for a fixed time (24 h); then CD36
      expression was determined using Western blots. CD36 expression was significantly
      decreased by ET in a time- and dose-dependent manner. This inhibitory effect was
      prevented by the ET(A) receptor antagonist BQ-610 (10 microM) but not the ET(B)
      receptor antagonist BQ-788 (10 microM). To further explore the underlying
      mechanisms of ET-1 action, we examined the involvement of the tyrosine kinase
      mediated and MAPK-mediated pathways. The inhibitory effect of ET-1 on CD36
      protein expression was blocked by inhibition of tyrosine kinase activation by use
      of genistein (100 microM) and by the ERK inhibitor PD-98059 (75 microM) but not
      by the p38 MAPK inhibitor SB-203580 (20 microM). In conclusion, we have
      demonstrated that ET-1, acting via the ET(A) receptor, suppresses CD36 protein
      expression in VSMCs by activation of the tyrosine kinase and ERK pathways.

PMID- 16985265
TI  - Independent component analysis of dynamic contrast-enhanced computed tomography
      images.
AB  - Independent component analysis (ICA) was applied on dynamic contrast-enhanced
      computed tomography images of cerebral tumours to extract spatial component maps
      of the underlying vascular structures, which correspond to different haemodynamic
      phases as depicted by the passage of the contrast medium. The locations of
      arteries, veins and tumours can be separately identified on these spatial
      component maps. As the contrast enhancement behaviour of the cerebral tumour
      differs from the normal tissues, ICA yields a tumour component map that reveals
      the location and extent of the tumour. Tumour outlines can be generated using the
      tumour component maps, with relatively simple segmentation methods.

PMID- 16985266
TI  - Monte Carlo microdosimetry of 188Re- and 131I-labelled anti-CD20.
AB  - The radiolabelled monoclonal antibody anti-CD20 has the property of binding to
      the CD20 antigen expressed on the cell surface of B-lymphocytes, thus making it a
      useful tool in the treatment of non-Hodgkin's lymphoma. In this work, the event
      by-event Monte Carlo code NOREC is used to calculate the single-event
      distribution function f(1)(z) in the cell nucleus using the beta spectra of the
      (188)Re and (131)I radionuclides. The simulated geometry consists of two
      concentric spheres representing the nucleus and the cell surface embedded in a
      semi-infinite water medium. An isotropic point source was placed on the cell
      surface to simulate the binding of the anti-CD20 labelled with either (188)Re or
      (131)I. The simulations were carried out for two combinations of cell surface and
      nucleus radii. A method was devised that allows one to calculate the contribution
      of betas of energy greater than 1 MeV, which cannot be simulated by the NOREC
      code, to the single-event distribution function. It is shown that disregarding
      this contribution leads to an overestimation of the frequency-mean specific
      energy of the order of 9-12%. In general, the antibody radiolabelled with (131)I
      produces single-event distribution functions that yield higher frequency-mean
      specific energies.

PMID- 16985267
TI  - The use of MR B+1 imaging for validation of FDTD electromagnetic simulations of
      human anatomies.
AB  - In this study, MR B(+)(1) imaging is employed to experimentally verify the
      validity of FDTD simulations of electromagnetic field patterns in human
      anatomies. Measurements and FDTD simulations of the B(+)(1) field induced by a 3
      T MR body coil in a human corpse were performed. It was found that MR B(+)(1)
      imaging is a sensitive method to measure the radiofrequency (RF) magnetic field
      inside a human anatomy with a precision of approximately 3.5%. A good correlation
      was found between the B(+)(1) measurements and FDTD simulations. The measured
      B(+)(1) pattern for a human pelvis consisted of a global, diagonal modulation
      pattern plus local B(+)(1) heterogeneties. It is believed that these local
      B(+)(1) field variations are the result of peaks in the induced electric
      currents, which could not be resolved by the FDTD simulations on a 5 mm(3)
      simulation grid. The findings from this study demonstrate that B(+)(1) imaging is
      a valuable experimental technique to gain more knowledge about the dielectric
      interaction of RF fields with the human anatomy.

PMID- 16985268
TI  - Velocity encoding versus acceleration encoding for pressure gradient estimation
      in MR haemodynamic studies.
AB  - Many methods have been proposed to extract pressure gradient maps from magnetic
      resonance (MR) images. They were based on the resolution of the haemodynamic
      model of Navier-Stokes and needed the flow acceleration to be known. Most used
      velocity data acquisition and computed acceleration from temporal and spatial
      derivatives of the velocity field. However, MR sequences have been developed in
      order to acquire the acceleration field directly. Here we compared direct MR
      measurements of acceleration field components with those calculated from MR
      velocity acquisitions. Two experimental phantoms were used to separately evaluate
      the inertial and convective components of the acceleration. Mathematical
      simulation of the convective phantom further explained the origin of the noise
      generated by the spatial and temporal derivatives of the velocity data, and the
      misregistration artefacts due to MR sequences. We found that direct measurement
      of the acceleration field generates less noise and fewer artefacts than
      calculation from velocity derivatives.

PMID- 16985269
TI  - A computer-aided temporal and dynamic subtraction technique of the liver for
      detection of small hepatocellular carcinomas on abdominal CT images.
AB  - It is often difficult for radiologists to identify small hepatocellular
      carcinomas (HCCs) due to insufficient contrast enhancement. Therefore, we have
      developed a new computer-aided temporal and dynamic subtraction technique to
      enhance small HCCs, after automatically selecting images set at the same
      anatomical position from the present (non-enhanced and arterial-phase CT images)
      and previous images. The present study was performed with CT images from 14
      subjects. First, we used template-matching based on similarities in liver shape
      between the present (non-enhanced and arterial-phase CT images) and previous
      arterial-phase CT images at the same position. Temporal subtraction images were
      then obtained by subtraction of the previous image from the present image taken
      at the same position of the liver. Dynamic subtraction images were also obtained
      by subtraction of non-enhanced CT images from arterial-phase CT images taken at
      the same position of the liver. Twenty-one of 22 nodules (95.5%) with contrast
      enhancement were visualized in temporal and dynamic subtraction images. Compared
      with present arterial-phase CT images, increases of 150% and 140% in nodule-to
      liver contrast were observed on dynamic and temporal subtraction images,
      respectively. These subtraction images may be useful as reference images in the
      detection of small moderately differentiated HCCs.

PMID- 16985270
TI  - Hybrid scatter correction applied to quantitative holmium-166 SPECT.
AB  - Ho-166 is a combined beta-gamma emitter of which the betas can be used
      therapeutically. From the 81 keV gammas of Ho-166, SPECT images can be obtained,
      which give opportunities to guide Ho-166 therapy. Accurate reconstruction of Ho
      166 images is currently hampered by photopeak-scatter in the patient, down
      scatter in the detector, collimator and patient caused by the 1.4 MeV photons and
      by bremsstrahlung. We developed and validated a method for quantitative SPECT of
      Ho-166 that involves correction for both types of scatter plus non-uniform
      attenuation correction using attenuation maps. Photopeak-scatter (S) is
      compensated for by a rapid 3D Monte Carlo (MC) method that is incorporated in
      ordered subset (OS) reconstruction of the emission data, together with
      simultaneous correction for attenuation (A) and detector response (D); this
      method is referred to as OS-ADS. Additionally, for correction of down-scatter, we
      use a 14 keV wide energy window centred at 118 keV (OS-ADSS). Due to a limited
      number of available energy windows, the same 118 keV energy window was used for
      down-scatter correction of the simultaneously acquired Gd-153 transmission data.
      Validations were performed using physical phantom experiments carried out on a
      dual-head SPECT system; Gd-153 transmission line sources were used for acquiring
      attenuation maps. For quantitative comparison of OS-ADS and OS-ADSS, bottles
      filled with Ho-166 were placed in both a cylindrical phantom and an
      anthropomorphic thorax phantom. Both OS-ADS and OS-ADSS were compared with an
      ordered subset reconstruction without any scatter correction (OS-AD).
      Underestimations of about 20% in the attenuation map were reduced to a few per
      cent after down-scatter correction. The average deviation from the true activity
      contained in the bottles was +72% with OS-AD. Using OS-ADS, this average
      overestimation was reduced to +28% and with OS-ADSS the deviation was further
      reduced to 16%. With OS-AD and OS-ADS, these numbers were more sensitive to the
      choice of volumes of interest than with OS-ADSS. For the reconstructed activity
      distributions, erroneous background activity found with OS-AD was reduced by a
      factor of approximately 2 by applying OS-ADS and reduced by a factor of
      approximately 4 by applying OS-ADSS. The combined attenuation, photopeak-scatter
      and down-scatter correction framework proposed here greatly enhanced the
      quantitative accuracy of Ho-166 imaging, which is of the uppermost importance for
      image-guided therapies. It is expected that the method, with adapted window
      settings, also can be applied to other isotopes with high energy peaks that
      contaminate the photopeak data, such as I-131 or In-111.

PMID- 16985271
TI  - An enhanced block matching algorithm for fast elastic registration in adaptive
      radiotherapy.
AB  - Image registration has many medical applications in diagnosis, therapy planning
      and therapy. Especially for time-adaptive radiotherapy, an efficient and accurate
      elastic registration of images acquired for treatment planning, and at the time
      of the actual treatment, is highly desirable. Therefore, we developed a fully
      automatic and fast block matching algorithm which identifies a set of anatomical
      landmarks in a 3D CT dataset and relocates them in another CT dataset by
      maximization of local correlation coefficients in the frequency domain. To
      transform the complete dataset, a smooth interpolation between the landmarks is
      calculated by modified thin-plate splines with local impact. The concept of the
      algorithm allows separate processing of image discontinuities like temporally
      changing air cavities in the intestinal track or rectum. The result is a fully
      transformed 3D planning dataset (planning CT as well as delineations of tumour
      and organs at risk) to a verification CT, allowing evaluation and, if necessary,
      changes of the treatment plan based on the current patient anatomy without time
      consuming manual re-contouring. Typically the total calculation time is less than
      5 min, which allows the use of the registration tool between acquiring the
      verification images and delivering the dose fraction for online corrections. We
      present verifications of the algorithm for five different patient datasets with
      different tumour locations (prostate, paraspinal and head-and-neck) by comparing
      the results with manually selected landmarks, visual assessment and consistency
      testing. It turns out that the mean error of the registration is better than the
      voxel resolution (2 x 2 x 3 mm(3)). In conclusion, we present an algorithm for
      fully automatic elastic image registration that is precise and fast enough for
      online corrections in an adaptive fractionated radiation treatment course.

PMID- 16985272
TI  - Extended collimator model for pencil-beam dose calculation in proton
      radiotherapy.
AB  - We have developed a simple collimator model to improve the accuracy of penumbra
      behaviour in pencil-beam dose calculation for proton radiotherapy. In this model,
      transmission of particles through a three-dimensionally extended opening of a
      collimator is calculated in conjunction with phase-space distribution of the
      particles. Comparison of the dose distributions calculated using the new three
      dimensional collimator model and the conventional two-dimensional model to
      lateral dose profiles experimentally measured with collimated proton beams showed
      the superiority of the new model over the conventional one.

PMID- 16985273
TI  - IMRT delivery to a moving target by dynamic MLC tracking: delivery for targets
      moving in two dimensions in the beam's eye view.
AB  - A new modification of the dynamic multileaf collimator (dMLC) delivery technique
      for intensity-modulated therapy (IMRT) is outlined. This technique enables the
      tracking of a target moving through rigid-body translations in a 2D trajectory in
      the beam's eye view. The accuracy of the delivery versus that of deliveries with
      no tracking and of 1D tracking techniques is quantified with clinically derived
      intensity-modulated beams (IMBs). Leaf trajectories calculated in the target
      reference frame were iteratively synchronized assuming regular target motion.
      This allowed the leaves defined in the lab-reference frame to simultaneously
      follow the target motion and to deliver the required IMB without violation of the
      leaf maximum-velocity constraint. The leaves are synchronized until the gradient
      of the leaf position at every instant is less than a calculated maximum. The
      delivered fluence in the target-reference frame was calculated with a simple
      primary-fluence model. The new 2D tracking technique was compared with the
      delivered fluence produced by no-tracking deliveries and by 1D tracking
      deliveries for 33 clinical IMBs. For the clinical IMBs normalized to a maximum
      fluence of 200 MUs, the rms difference between the desired and the delivered IMB
      was 15.6 +/- 3.3 MU for the case of a no-tracking delivery, 7.9 +/- 1.6 MU for
      the case where only the primary component of motion was corrected and 5.1 +/- 1.1
      MU for the 2D tracking delivery. The residual error is due to interpolation and
      sampling effects. The 2D tracking delivery technique requires an increase in the
      delivery time evaluated as between 0 and 50% of the unsynchronized delivery time
      for each beam with a mean increase of 13% for the IMBs tested. The 2D tracking
      dMLC delivery technique allows an optimized IMB to be delivered to moving targets
      with increased accuracy and with acceptable increases in delivery time. When
      combined with real-time knowledge of the target motion at delivery time, this
      technique facilitates improved target conformality relative to no-tracking
      deliveries and allows PTV margin reduction.

PMID- 16985274
TI  - Dose variations with varying calculation grid size in head and neck IMRT.
AB  - Ever since the advent and development of treatment planning systems, the
      uncertainty associated with calculation grid size has been an issue. Even to this
      day, with highly sophisticated 3D conformal and intensity-modulated radiation
      therapy (IMRT) treatment planning systems (TPS), dose uncertainty due to grid
      size is still a concern. A phantom simulating head and neck treatment was
      prepared from two semi-cylindrical solid water slabs and a radiochromic film was
      inserted between the two slabs for measurement. Plans were generated for a 5,400
      cGy prescribed dose using Philips Pinnacle(3) TPS for two targets, one shallow (
      approximately 0.5 cm depth) and one deep ( approximately 6 cm depth). Calculation
      grid sizes of 1.5, 2, 3 and 4 mm were considered. Three clinical cases were also
      evaluated. The dose differences for the varying grid sizes (2 mm, 3 mm and 4 mm
      from 1.5 mm) in the phantom study were 126 cGy (2.3% of the 5,400 cGy dose
      prescription), 248.2 cGy (4.6% of the 5,400 cGy dose prescription) and 301.8 cGy
      (5.6% of the 5,400 cGy dose prescription), respectively for the shallow target
      case. It was found that the dose could be varied to about 100 cGy (1.9% of the
      5,400 cGy dose prescription), 148.9 cGy (2.8% of the 5,400 cGy dose prescription)
      and 202.9 cGy (3.8% of the 5,400 cGy dose prescription) for 2 mm, 3 mm and 4 mm
      grid sizes, respectively, simply by shifting the calculation grid origin. Dose
      difference with a different range of the relative dose gradient was evaluated and
      we found that the relative dose difference increased with an increase in the
      range of the relative dose gradient. When comparing varying calculation grid
      sizes and measurements, the variation of the dose difference histogram was
      insignificant, but a local effect was observed in the dose difference map.
      Similar results were observed in the case of the deep target and the three
      clinical cases also showed results comparable to those from the phantom study.

PMID- 16985275
TI  - The influence of output measurement time interval and tolerance on treatment dose
      deviation in photon external beam radiotherapy.
AB  - A method was developed to estimate the spread of treatment doses due to a given
      output measurement, time interval and action level in external photon beam
      radiotherapy. The method exploits empirical or simulated data of both output
      stability and the reproducibility of the absolute output measurements and
      relative constancy checks. The spread of an output and the probability that an
      output is outside the predefined tolerance limits were estimated for different
      quality control procedures of the output. The use of internationally recommended
      output measurement intervals of 3, 1 and 0.25 months together with an action
      level of +/-2% results in the out-of-tolerance probability up to 49%, 26% and 3%,
      respectively, while the output is kept within up to +/-5.5%, +/-4.0% and +/-2.0%,
      respectively. It was also found that the action level has more prominent relative
      influence than the measurement interval. The results suggest that similar
      treatment quality can be achieved by doubling the output measurement time
      interval and lowering the action level from +/-2% to +/-1.5% and the constancy
      check action level from +/-3% to +/-2%.

PMID- 16985276
TI  - An in vitro study of magnetic particle targeting in small blood vessels.
AB  - The magnetic guidance and capture of particles inside the human body, via the
      circulatory system, is a novel method for the targeted delivery of drugs. This
      experimental study confirms in vitro that a dipolar capturing device, based on
      high-energy magnets with an active space of 8.7 cm x 10 cm x 10 cm, retains
      colloidal magnetic particles (MPs) (<30 nm) injected in the capillary tubes,
      where flow velocities are comparable to that encountered in the capillary beds of
      tumours (<0.5 cm s(-1)). The build-up of the deposition of the MPs was
      investigated using video imaging techniques that enabled continuous monitoring of
      the blocking of the vessel whilst simultaneously recording the colloid's flow
      rate. The parameters of practical importance (length of MP deposit, time of
      capillary blocking) were estimated and were found to be dependent on the initial
      fluid velocity, the MP concentration and the distance between the capillary tube
      and the polar magnetic pieces. Although the tube used in this experiment is
      larger (diameter = 0.75 mm, length = 100 mm) than that of real capillaries
      (diameter = 0.01 mm, length approximately 1.5 mm), the flow velocities chosen
      were similar to those encountered in the capillary beds of tumours and the
      length/diameter ratio was approximately equal (133 for the present set-up, 100
      150 for real capillaries). In these circumstances and using the same magnetic
      field conditions (intensity, gradient) and MPs, there is close similarity with
      magnetic capture in a microscopic capillary system. Moreover, the macroscopic
      system permits analysis of the distribution of MPs in the active magnetic space,
      and consequently the maximum targetable volume. This study revealed that the
      capture of particles within the active space was strongly influenced by the
      gradient of the magnetic field and the flow velocity. Thus, when the magnetic
      field gradient had medium values (0.1-0.3 T cm(-1)) and the fluid velocity was
      small (0.15 cm s(-1)), the particles were captured in small, compact and stable
      deposits (L < 4 cm) and the time necessary for blocking of the capillary was <150
      s. Doubling the value for the flow velocity did not influence significantly
      either the length of MP deposits nor the blocking time. However, lower gradients
      (<0.1 T cm(-1)) and larger velocities (0.3-0.9 cm s(-1)) result in the formation
      of larger deposits (4 cm < L < 10 cm) that are unstable at the beginning of the
      capture process. These large deposits do become stable given sufficient time for
      the deposition process to take place in conjunction with a decrease in the flow
      rate. As a consequence, the time necessary for blocking of the capillary
      increased up to 450 s. Decreasing the MP concentration from 0.02 g cm(-3) to
      0.005 g cm(-3) decreased the deposit lengths by approximately 20% and doubled the
      values of the blocking time. The maximum targetable volume obtained by the
      present method is approximately 350 cm(3), which corresponds to medium-sized
      tumours. The capillary vessels were blocked only for the situation that occurs
      for microcirculation within a tumour. This reduces the concentration of MPs
      trapped within the normal tissues, which occurs when using particles of
      micrometre size. This work showed the potential of using colloidal MPs and
      dipolar magnetic devices for treatment of human patients, when the affected sites
      are positioned at medium distances from the surface of the body (e.g. head, neck,
      breast, hands and legs).

PMID- 16985277
TI  - Repair dependent radiation survival: a stochastic model with Euler gamma function
      solutions.
AB  - The probability of survival of cells or viruses exposed to various forms of
      radiation is expressed as a function of the probability that a given cell will
      receive a certain number of lethal damages, the average probability that each
      such damage is repairable, and an upper bound on the repair capacity of each
      cell. All lethal damages are presumed induced as a linear function of dose. The
      probability of survival is found to be the product of a single exponential, which
      reflects inactivation by unrepairable lethal damages and dominates at low doses,
      and an Euler gamma function, which reflects inactivation due to repairable
      damages formed in excess of the upper bound on repair capacity. Computational
      procedures obtain stochastic parameters from published survival data for the
      inactivation of bacterial, yeast and mammalian cells exposed to ionizing or
      ultraviolet radiation, including split-dose experiments. The survival of cells
      exposed to photodynamic therapy is analysed assuming that lethal damages cannot
      be repaired, but more than one may be required for inactivation.

PMID- 16985278
TI  - Adapting radiotherapy to hypoxic tumours.
AB  - In the current work, the concepts of biologically adapted radiotherapy of hypoxic
      tumours in a framework encompassing functional tumour imaging, tumour control
      predictions, inverse treatment planning and intensity modulated radiotherapy
      (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging
      (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The
      tracer concentration in the tumour was assumed related to the oxygen tension and
      compared to Eppendorf histograph measurements. Based on the pO(2)-related images
      derived from the MR analysis, the tumour was divided into four compartments by a
      segmentation procedure. DICOM structure sets for IMRT planning could be derived
      thereof. In order to display the possible advantages of non-uniform tumour doses,
      dose redistribution among the four tumour compartments was introduced. The dose
      redistribution was constrained by keeping the average dose to the tumour equal to
      a conventional target dose. The compartmental doses yielding optimum tumour
      control probability (TCP) were used as input in an inverse planning system, where
      the planning basis was the pO(2)-related tumour images from the MR analysis.
      Uniform (conventional) and non-uniform IMRT plans were scored both physically and
      biologically. The consequences of random and systematic errors in the
      compartmental images were evaluated. The normalized frequency distributions of
      the tracer concentration and the pO(2) Eppendorf measurements were not
      significantly different. 28% of the tumour had, according to the MR analysis,
      pO(2) values of less than 5 mm Hg. The optimum TCP following a non-uniform dose
      prescription was about four times higher than that following a uniform dose
      prescription. The non-uniform IMRT dose distribution resulting from the inverse
      planning gave a three times higher TCP than that of the uniform distribution. The
      TCP and the dose-based plan quality depended on IMRT parameters defined in the
      inverse planning procedure (fields and step-and-shoot intensity levels).
      Simulated random and systematic errors in the pO(2)-related images reduced the
      TCP for the non-uniform dose prescription. In conclusion, improved tumour control
      of hypoxic tumours by dose redistribution may be expected following hypoxia
      imaging, tumour control predictions, inverse treatment planning and IMRT.

PMID- 16985279
TI  - Analytical derivation of the point spread function for pinhole collimators.
AB  - The point spread function (PSF) of a pinhole collimator plays an important role
      in determining the resolution and characterizing the sensitivity of the accepted
      photons from a given point in the image space. The focus of this paper is to
      derive an analytical expression for the PSF of two different types of focusing
      pinhole collimators that are based on (1) right-circular double cones and (2)
      oblique-circular double cones. Conventionally, focusing pinhole collimators used
      in multi-pinhole SPECT were designed using right-circular double cones, as they
      were easier to fabricate. In this work, a novel focusing collimator consisting of
      oblique-circular double cones was designed and its properties were studied in
      detail with respect to right-circular double-cone based collimators. The main
      advantage of determining the PSF is the fact that they can be used to accurately
      model the PSF during the reconstruction, thereby improving the resolution of the
      reconstructed image. The PSF of the focusing collimators based on oblique
      circular cones were found to be almost shift invariant for low and medium energy
      photons (below 200 keV). This property is very advantageous as algorithms such as
      slice-by-slice reconstruction can be used for resolution recovery thereby
      drastically reducing the reconstruction time. However, the PSF of focusing
      oblique-circular double cones (FOCDC) for higher energy photons were found to be
      asymmetric and hence need to be modelled more accurately during the
      reconstruction. On the other hand, the PSF for the right-circular cone based
      collimators were found to be asymmetric for all energy levels. However, due to
      the smaller acceptance angle used, the number of penetration photons was found to
      be far less than that observed for oblique-circular cones. This results in a
      smaller PSF making right-circular cone based collimators preferable for high
      resolution small animal imaging, especially where very small pinhole diameters
      are used. The analytically derived PSF for both collimators were validated using
      a ray-tracing based Monte Carlo approach and found to agree well with a mean
      square error of less than 1%.

PMID- 16985280
TI  - Characterization of the electromagnetic near-field absorption in layered
      biological tissue in the frequency range from 30 MHz to 6,000 MHz.
AB  - Currently, standards for the compliance testing of wireless devices are being
      extended to cover a wider frequency band and different usage patterns of mobile
      phones as well as of novel body-worn and handheld devices. As a consequence, not
      only the head but also strongly varying tissue distributions of the body are
      exposed to electromagnetic radiation. Several authors have reported changes in
      the SAR absorption of body tissue due to the presence of a low permittivity fat
      layer. This paper identifies two different effects which can lead to increased
      SAR in layered tissue in comparison to the SAR assessed using homogeneous tissue
      simulating liquid: (1) for larger distances between the tissue and the antenna,
      standing wave effects occur depending on the frequency and fat layer thickness.
      (2) In the very close near-field (distances approximately lambda/40), reactive E
      field components lead to high local absorption in the skin. The latter effect
      occurs at lower frequencies and depends on the antenna type. Modification of the
      parameters of the homogeneous liquids cannot compensate for these effects.
      However, a conservative exposure estimate can be obtained by applying a
      multiplication factor between 1 and 3 to the values assessed using current
      experimental dosimetric techniques.

PMID- 16985281
TI  - Clinical comparison of head and neck and prostate IMRT plans using absorbed dose
      to medium and absorbed dose to water.
AB  - Conventional photon radiation therapy dose-calculation algorithms typically
      compute and report the absorbed dose to water (D(w)). Monte Carlo (MC) dose
      calculation algorithms, however, generally compute and report the absorbed dose
      to the material (D(m)). As MC-calculation algorithms are being introduced into
      routine clinical usage, the question as to whether there is a clinically
      significant difference between D(w) and D(m) remains. The goal of the current
      study is to assess the differences between dose-volume indices for D(m) and D(w)
      MC-calculated IMRT plans. Ten head-and-neck (H&N) and ten prostate cancer
      patients were selected for this study. MC calculations were performed using an
      EGS4-based system. Converting D(m) to D(w) for MC-based calculations was
      accomplished as a post-MC calculation process. D(w) and D(m) results for target
      and critical structures were evaluated using the dose-volume-based indices. For
      H&N IMRT plans, systematic differences between dose-volume indices computed with
      D(w) and D(m) were up to 2.9% for the PTV prescription dose (D(98)), up to 5.8%
      for maximum (D(2)) dose to the PTV and up to 2.7% for the critical structure dose
      indices. For prostate IMRT plans, the systematic differences between D(w)- and
      D(m)-based computed indices were up to 3.5% for the prescription dose (D(98)) to
      the PTVs, up to 2.0% for the maximum (D(2)) dose to the PTVs and up to 8% for the
      femoral heads due to their higher water/bone mass stopping power ratio. This
      study showed that converting D(m) to D(w) in MC-calculated IMRT treatment plans
      introduces a systematic error in target and critical structure DVHs. In some
      cases, this systematic error may reach up to 5.8% for H&N and 8.0% for prostate
      cases when the hard-bone-containing structures such as femoral heads are present.
      Ignoring differences between D(m) and D(w) will result in systematic dose errors
      ranging from 0% to 8%.

PMID- 16985282
TI  - Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for
      prostate radiotherapy targeting.
AB  - Several measurement techniques have been developed to address the capability for
      target volume reduction via target localization in image-guided radiotherapy;
      among these have been ultrasound (US) and fiducial marker (FM) software-assisted
      localization. In order to assess interchangeability between methods, US and FM
      localization were compared using established techniques for determination of
      agreement between measurement methods when a 'gold-standard' comparator does not
      exist, after performing both techniques daily on a sequential series of patients.
      At least 3 days prior to CT simulation, four gold seeds were placed within the
      prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D
      (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate
      position; US prostate targeting was performed on each patient using the SonArray
      (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of
      skin marks. Directional shifts were then calculated by each respective system in
      the X, Y and Z dimensions before each daily treatment fraction, previous to any
      treatment or couch adjustment, as well as a composite vector of displacement.
      Directional shift agreement in each axis was compared using Altman-Bland limits
      of agreement, Lin's concordance coefficient with Partik's grading schema, and
      Deming orthogonal bias-weighted correlation methodology. 1,019 software-assisted
      shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in
      X, Y and Z axes were +/-9.4 mm, +/-11.3 mm and +/-13.4, respectively. Three
      dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures.
      In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming
      regression detected proportional bias in both directional axes and three
      dimensional vectors. Our data suggest substantial differences between US and FM
      image-guided measures and subsequent suggested directional shifts. Analysis
      reveals that the vast majority of all individual US and FM directional measures
      may be expected to agree with each other within a range of 1-1.5 cm. Since
      neither system represents a gold standard, clinical judgment must dictate whether
      such a difference is of import. As IMRT protocols seek dose escalation and PTV
      reduction predicated on US- and FM-guided imaging, future studies are needed to
      address these potential clinically relevant issues regarding the
      interchangeability and accuracy of novel positional verification techniques.
      Comparison series with multiple image-guidance systems are needed to refine
      comparisons between targeting methods. However, we do not advocate
      interchangeability of US and FM localization methods.

PMID- 16985283
TI  - Influence of ambient humidity on the current delivered by air-vented ionization
      chambers revisited.
AB  - The influence of ambient humidity on the current delivered by a vented ionization
      chamber has been re-investigated. A Nucletron 077.091 well-type chamber together
      with a (192)Ir HDR brachytherapy source was enclosed in a climatic test chamber
      and the current was recorded for various humidity values. Great care has been
      taken for the design of the experimental setup in order to obtain reliable
      measurements of currents and humidity values inside the chamber active volume. A
      +/-0.35% linear variation of the measured currents has been observed over a
      common range of humidities. This result is larger than the expected variation. No
      formal explanation of such a discrepancy has been found yet, however the present
      results could lead to a set of recommendations.

PMID- 16985284
TI  - Modelling the impact of blood flow on the temperature distribution in the human
      eye and the orbit: fixed heat transfer coefficients versus the Pennes bioheat
      model versus discrete blood vessels.
AB  - Prediction of the temperature distribution in the eye depends on how the impact
      of the blood flow is taken into account. Three methods will be compared: a
      simplified eye anatomy that applies a single heat transfer coefficient to
      describe all heat transport mechanisms between the sclera and the body core, a
      detailed eye anatomy in which the blood flow is accounted for either by the
      bioheat approach, or by including the discrete vasculature in the eye and the
      orbit. The comparison is done both for rabbit and human anatomies, normo
      thermally and when exposed to homogeneous power densities. The first simplified
      model predicts much higher temperatures than the latter two. It was shown that
      the eye is very hard to heat when taking physiological perfusion correctly into
      account. It was concluded that the heat transfer coefficient describing the heat
      transport from the sclera to the body core reported in the literature for the
      first simplified model is too low. The bioheat approach is appropriate for a
      first-order approximation of the temperature distribution in the eye when exposed
      to a homogeneous power density, but the discrete vasculature down to 0.2 mm in
      diameter needs to be taken into account when the heterogeneity of the temperature
      distribution at a mm scale is of interest.

PMID- 16985285
TI  - Radiation risk assessment in neonatal radiographic examinations of the chest and
      abdomen: a clinical and Monte Carlo dosimetry study.
AB  - Seeking to assess the radiation risk associated with radiological examinations in
      neonatal intensive care units, thermo-luminescence dosimetry was used for the
      measurement of entrance surface dose (ESD) in 44 AP chest and 28 AP combined
      chest-abdominal exposures of a sample of 60 neonates. The mean values of ESD were
      found to be equal to 44 +/- 16 microGy and 43 +/- 19 microGy, respectively. The
      MCNP-4C2 code with a mathematical phantom simulating a neonate and appropriate x
      ray energy spectra were employed for the simulation of the AP chest and AP
      combined chest-abdominal exposures. Equivalent organ dose per unit ESD and energy
      imparted per unit ESD calculations are presented in tabular form. Combined with
      ESD measurements, these calculations yield an effective dose of 10.2 +/- 3.7
      microSv, regardless of sex, and an imparted energy of 18.5 +/- 6.7 microJ for the
      chest radiograph. The corresponding results for the combined chest-abdominal
      examination are 14.7 +/- 7.6 microSv (males)/17.2 +/- 7.6 microSv (females) and
      29.7 +/- 13.2 microJ. The calculated total risk per radiograph was low, ranging
      between 1.7 and 2.9 per million neonates, per film, and being slightly higher for
      females. Results of this study are in good agreement with previous studies,
      especially in view of the diversity met in the calculation methods.

PMID- 16985286
TI  - Contrast and spatial resolution in MREIT using low amplitude current.
AB  - Magnetic resonance-electrical impedance tomography employs low amplitude currents
      injected or induced inside an object. The additional magnetic field due to these
      currents results in a phase in the MR images. In this study, a modified fast spin
      echo sequence was used to measure this magnetic field, which is obtained by
      scaling the MR phase image. A finite element method with first order triangular
      elements was used for the solution of the forward problem. An iterated
      sensitivity matrix-based algorithm was developed for the inverse problem. The
      resulting ill-conditioned matrix equation was regularized using the Tikhonov
      method and solved using a conjugate gradient solver. The spatial and contrast
      resolution of the technique was tested using agarose gel phantoms. A circular
      phantom with 7 cm diameter and 1 cm thickness is used in the phantom experiments.
      The amplitude of the injected current was 1 mA. 3, 5 and 8 mm diameter insulators
      and high conductor objects are used for the spatial resolution study and an
      average full-width half-maximum value of 4.7 mm is achieved for the 3 mm
      insulator case. For the contrast analysis, the conductivity of a 15 mm object is
      varied between 44% and 500% with respect to the background and results are
      compared to the ideal reconstruction.

PMID- 16985287
TI  - Performance of dedicated emission mammotomography for various breast shapes and
      sizes.
AB  - We evaluate the effect of breast shape and size and lesion location on a
      dedicated emission mammotomography system developed in our lab. The hemispherical
      positioning gantry allows ample flexibility in sampling a pendant, uncompressed
      breast. Realistic anthropomorphic torso (which includes the upper portion of the
      arm) and breast phantoms draw attention to the necessity of using unique camera
      trajectories (orbits) rather than simple circular camera trajectories. We have
      implemented several novel three-dimensional (3D) orbits with fully contoured
      radius-of-rotation capability for compensating for the positioning demands that
      emerge from different breast shapes and sizes. While a general orbit design may
      remain the same between two different breasts, the absolute polar tilt range and
      radius-of-rotation range may vary. We have demonstrated that using 3D orbits with
      increased polar camera tilt, lesions near the chest wall can be visualized for
      both large and small sized breasts (325 ml to 1,060 ml), for a range of intrinsic
      contrasts (three to ten times higher activity concentration in the lesion than
      breast background). Overall, nearly complete 3D acquisition schemes yield image
      data with relatively high lesion SNRs and contrasts and with minimal distortion
      of the uncompressed breast shape.

PMID- 16985288
TI  - Genetic diversity and epizootiology of Chlamydophila psittaci prevalent among the
      captive and feral avian species based on VD2 region of ompA gene.
AB  - To study genetic diversity and occurrence of Chlamydophila psittaci, a total of
      1,147 samples from 11 avian orders including 53 genera and 113 species of feral
      and captive birds were examined using ompA gene based nested PCR. Three types of
      chlamydiae: C. psittaci (94.12%), C. abortus (4.41%) and unknown Chlamydophila
      sp. (1.47%) were identified among 68 (5.93%) positive samples (Psittaciformes-59,
      Ciconiiformes-8 and Passeriformes-1). Based on nucleotide sequence variations in
      the VD2 region of ompA gene, all 64 detected C. psittaci strains were grouped
      into 4 genetic clusters. Clusters I, II, III and IV were detected from 57.35%,
      19.12%, 10.29% and 7.35% samples respectively. A single strain of unknown
      Chlamydophila sp. was found phylogenetically intermediate between Chlamydophila
      species infecting avian and mammalian hosts. Among Psittaciformes, 28 out of 81
      tested species including 10 species previously unreported were found to be
      chlamydiae positive. Chlamydiosis was detected among 8.97% sick and 48.39% dead
      birds as well 4.43% clinically normal birds. Therefore, it was observed that
      though various genetically diverse chlamydiae may cause avian chlamydiosis, only
      a few C. psittaci strains are highly prevalent and frequently associated with
      clinical/subclinical infections.

PMID- 16985289
TI  - The postantifungal effect (PAFE) of itraconazole, in comparison with those of
      miconazole and fluconazole, on Candida Species.
AB  - To study the postantifungal effect (PAFE) of itraconazole (ITCZ) against Candida
      species, we quantitated it using a newly introduced parameter T/C(T=time required
      for the drug-treated culture to reach 5-fold increase in turbidity; C=time
      required for the drug-free control culture to reach 5-fold increase in turbidity)
      referred as PAFE index and compared the results with those obtained for two other
      azole antifungal drugs fluconazole (FLCZ) and miconazole (MCZ). The mean values
      of PAFE index for ITCZ against three C. albicans strains were 1.28, 1.45, and
      1.60 when exposed to the drug for 1 hr at concentrations of 1 x MIC, 2 x MIC and
      4 x MIC, respectively. These values are similar to those for MCZ and appreciably
      higher than those for FLCZ. PAFE index values for ITCZ against each single strain
      of three non-albicans Candida species exposed to 2 x MIC of the drug for 1 hr
      were: 1.22 with C. glabrata, 1.63 with C. parapsilosis, and 3.90 with C.
      tropicalis. Again, comparable values were obtained for MCZ and lower values for
      FLCZ. The drug concentration for exposure and the duration of exposure only
      slightly or scarcely affected the PAFE of ITCZ, although the magnitude of the
      PAFE considerably varied among different strains or species tested. In general,
      ITCZ, as well as MCZ, produced greater extents of PAFE than those for FLCZ
      against C. albicans and several non-albicans Candida species.

PMID- 16985290
TI  - Mechanism of enhanced hematopoietic response by soluble beta-glucan SCG in
      cyclophosphamide-treated mice.
AB  - SCG is a major 6-branched 1,3-beta-D-glucan in Sparassis crispa Fr. SCG shows
      antitumor activity and also enhances the hematopoietic response in
      cyclophosphamide (CY)-treated mice. In the present study, the molecular mechanism
      of the enhancement of the hematopoietic response was investigated. The levels of
      interferon-(IFN-)gamma, tumor necrosis factor-(TNF-)alpha, granulocyte-macrophage
      colony stimulating factor (GM-CSF), interleukin-(IL-) 6 and IL-12p70 were
      significantly increased by SCG in CY-treated mice. GM-CSF production in the
      splenocytes from the CY-treated mice was higher than that in normal mice
      regardless of SCG stimulation. Neutralizing GM-CSF significantly inhibited the
      induction of IFN-gamma, TNF-alpha and IL-12p70 by SCG. The level of cytokine
      induction by SCG was regulated by the amount of endogenous GM-CSF produced in
      response to CY treatment in a dose-dependent manner. The expression of beta
      glucan receptors, such as CR3 and dectin-1, was up-regulated by CY treatment.
      Blocking dectin-1 significantly inhibited the induction of TNF-alpha and IL-12p70
      production by SCG. Taken together, these results suggest that the key factors in
      the cytokine induction in CY-treated mice were the enhanced levels of both
      endogenous GM-CSF production and dectin-1 expression.

PMID- 16985291
TI  - Preliminary human study for possible alteration of serum immunoglobulin E
      production in perennial allergic rhinitis with fermented milk prepared with
      Lactobacillus gasseri TMC0356.
AB  - The fermented milk prepared with Lactobacillus gasseri TMC0356 was administered
      at 200 ml per day for 4 weeks to 15 subjects with high serum IgE levels and
      perennial allergic rhinitis. The serum total IgE concentration was significantly
      reduced after 28 days' exposure to the fermented milk (P <0.05) compared to that
      before the intervention. The serum IgE specific to Acari and those to Japanese
      cedar pollen also significantly declined (P <0.05). T helper 1 (Th1) cells in the
      composition of their peripheral blood mononuclear cells (PBMCs) significantly
      increased after 14 days (P <0.01) and after 28 days (P <0.05). These results
      suggest that the fermented milk prepared with L. gasseri TMC0356 may alter serum
      IgE concentration, at least partly by enhancement of Th1 immune responses of the
      subjects with high concentration of serum IgE. However, further studies are still
      necessary to know the underlying mechanisms by which the tested fermented milk
      could influence the host immunity.

PMID- 16985292
TI  - Development of a real-time PCR assay for detection of gyrA mutations associated
      with reduced susceptibility to ciprofloxacin in Salmonella enterica serovar typhi
      and paratyphi A.
AB  - A real-time PCR assay with the cycling probe method was used to detect mutations
      at codons 83 and 87 in the DNA gyrase A subunit encoded by gyrA in Salmonella
      enterica serovar Typhi and Paratyphi A clinical isolates. The susceptibility
      estimated from the results of the gyrA mutation assay was consistent with that
      identified by the culture method using an E-test. This assay allows rapid
      screening of S. enterica serovar Typhi and Paratyphi A with reduced
      susceptibility to ciprofloxacin.

PMID- 16985293
TI  - Typing of bfpA genes of enteropathogenic Escherichia coli isolated in Thailand
      and Japan by heteroduplex mobility assay.
AB  - We developed a rapid genetic approach for screening bfpA variants of
      enteropathogenic E. coli(EPEC) using a heteroduplex mobility assay (HMA). A total
      of 204 human EPEC strains were isolated in Thailand and Japan. Of 34 bfpA
      positive EPEC strains, bfpA variants were classified into 5 HMA-types. Different
      HMA-types were found in EPEC of the same serotypes. The results suggest that HMA
      is a simple and easy method to analyze polymorphism of bfpA gene, and can be used
      in laboratories without large apparatus such as sequencers.

PMID- 16985294
TI  - CD8+ T cells play disparate roles in the induction and the effector phases of
      murine experimental allergic conjunctivitis.
AB  - Although CD4+ Th2 cells clearly play an essential role in the development of
      experimental allergic diseases, the functions CD8+ T cells may have in these
      diseases have been investigated less extensively and remain controversial. Here,
      we investigated the roles of CD8+ T cells in the development of experimental
      allergic conjunctivitis (EC). EC was induced in CD8alpha-deficient (CD8KO) mice
      and wild-type (WT) mice by active immunization with short ragweed pollen (RW)
      followed by challenge with RW-containing eye drops. Alternatively, EC was induced
      by transferring RW-primed splenocytes followed by RW challenge. With regard to
      actively immunized mice, CD8KO mice showed significantly less severe eosinophil
      infiltration of the conjunctiva and lower total IgE levels, although the levels
      of the other Igs were equivalent between the two strains. Cytokine production by
      cultured splenocytes also did not differ, but the WT conjunctivas showed
      upregulated IL-5 and IL-6 expression and greater upregulation of IL-4 expression
      than the conjunctivas of CD8KO mice. Thus, CD8+ T cells may play a significant
      role during the induction phase by aiding IgE production and the generation of
      Th2 cytokines in the conjunctiva, thus promoting the development of EC. In
      contrast, splenocytes from CD8KO mice induced significantly more severe EC in WT
      mice than cells from WT mice. In addition, transfer of RW-primed splenocytes
      induced significantly more severe eosinophil infiltration in CD8KO recipient
      mice. Thus, CD8+ T cells promote the development of EC during the induction
      phase, but suppress it during the effector phase.

PMID- 16985295
TI  - Identification and molecular characterization of an N-Acetylmuraminidase, Aml,
      involved in Streptococcus mutans cell separation.
AB  - We previously demonstrated Streptococcus mutans produces two bacteriolytic
      enzymes of 100 kDa and 80 kDa (G. Yoshimura et al. Microbiol. Immunol. 48, 465
      469, 2004). Here, we identified the protein sequence of these enzymes and found
      they come from a single gene product designated as automutanolysin (Aml). Aml has
      a modular design where the N-terminus contains five 13-amino-acid repeats and a C
      terminal enzyme active domain. Aml selectively lyses S. mutans and S. sobrinus
      but no other oral streptococci. This suggests Aml possesses strong substrate
      specificity towards cariogenic bacteria present in the human oral cavity.
      Analysis of S. mutans peptidoglycan fragments released by Aml shows the enzyme is
      an N-acetylmuraminidase. We found Ca(2+) enhances the activity; and EGTA, EDTA
      and iodoacetic acid inhibit the activity. The optimum pH range for lytic activity
      was 6 to 7. Disruption of the aml gene in S. mutans results in the formation of a
      longer bacterial cell chain length that was dispersed by the addition of a low
      concentration of Aml. This suggests Aml is involved in S. mutans cell separation.

PMID- 16985297
TI  - SARS: Challenge of the new century.

PMID- 16985296
TI  - Phylogenetic analysis of Bacillus cereus isolates from severe systemic infections
      using multilocus sequence typing scheme.
AB  - Bacillus cereus strains from cases of severe or lethal systemic infections,
      including respiratory symptoms cases, were analyzed using multilocus sequence
      typing scheme of B. cereus MLST database. The isolates were evenly distributed
      between the two main clades, and 60% of them had allele profiles new to the
      database. Half of the collection's strains clustered in a lineage neighboring
      Bacillus anthracis phylogenetic origin. Strains from lethal cases with
      respiratory symptoms were allocated in both main clades. This is the first report
      of strains causing respiratory symptoms to be identified as genetically distant
      from B. anthracis. The phylogenetic location of the presented here strains was
      compared with all previously submitted to the database isolates from systemic
      infections, and were found to appear in the same clusters where clinical isolates
      from other studies had been assigned. It seems that the pathogenic strains are
      forming clusters on the phylogenetic tree.

PMID- 16985298
TI  - Severe acute respiratory syndrome: the evolution of a new epidemic.

PMID- 16985299
TI  - Prevalence of autoantibodies in patients with hepatitis C virus infection in
      Oman.
AB  - BACKGROUND: HCV genotype patterns and HLA types in the Omani population may be
      unique. SUBJECTS AND METHODS: Tests for 12 different autoantibodies were carried
      out on 50 HCV-infected patients and on 27 HCV-seronegative controls. An
      immunoassay for the detection of anti-HCV antibodies was performed on patient and
      control sera. HCV PCR was carried out on those sera which were positive for HCV
      antibodies. RESULTS: All patients sera were positive for HCV antibodies and all
      control sera were negative. Sixty-six percent of patients were positive for at
      least one autoantibody. In contrast, only 33% of the controls showed positivity
      for one or more autoantibodies. CONCLUSION: This study found a significant
      difference in the prevalence of autoantibodies between patients and controls, and
      between organ- and non-organ specific autoantibodies among the patients. A
      comparison with autoantibody patterns reported for HCV-infected patients in other
      parts of the world suggest that patterns in HCV-infected individuals in the Omani
      population are unique.

PMID- 16985300
TI  - Five year experience in prenatal ultrasound diagnosis of esophageal atresia in
      Saudi Arabia.
AB  - BACKGROUND: Esophageal atresia (EA), with or without tracheoesophageal fistula
      (TOF) is one of the most correctable fetal anomalies if diagnosed antenatally by
      serial ultrasound. We retrospectively evaluated antenatal diagnoses by ultrasound
      of EA with or without TOF at our institution in Saudi Arabia. PATIENTS AND
      METHODS: We examined the records of mothers and infants with EA with or without
      TOF who were booked early and delivered at our institution during 1994 to 1998.
      Fetal diagnosis was based on level II serial ultrasound using a high-resolution
      ultrasound machine (n=78). RESULTS: In the 5-year period, there were 58 491 live
      births, with 1345 congenital abnormalities (2.3%) and 78 cases of EA with or
      without TOF (0.13%) diagnosed antenatally. The survival rate was 68% for women
      with vaginal deliveries and 60% for women with caesarean deliveries, so caesarean
      delivery did not improve outcome. The Apgar score was 7 or greater at 5 minutes
      in 65 cases (83.5%), which emphasizes the problems such patients develop after
      delivery. Death was caused by anomalies other than EA that were incompatible with
      life, or in the post-operative period, by septicemia, renal failure or cot death.
      CONCLUSIONS: Our study suggests that early antenatal booking, serial ultrasound
      and early antenatal diagnosis improves outcome in EA with or without TOF.

PMID- 16985301
TI  - Maternal and perinatal outcome of massive postpartum hemorrhage: a review of 33
      cases.
AB  - BACKGROUND: Postpartum hemorrhage is a significant contributor to maternal
      morbidity and mortality. PATIENTS AND METHODS: We evaluated maternal and
      perinatal outcome of primary massive postpartum hemorrhage. In a restrospective
      case analysis of 33 women with intractable postpartum hemorrhage initially
      managed either by hysterectomy or a conservative approach in a tertiary referral
      center between January 1, 1991 to December 30, 1998, we reviewed the procedures
      used as a primary or secondary attempt to arrest the hemorrhage. RESULTS: Medical
      and surgical measures were successful in controlling hemorrhage in 21 (63.6%) of
      the 33 women. Hemorrhage was successfully arrested by conservative surgery in 13
      cases, and by medical management in 8 cases. Emergency hysterectomy was performed
      in 12 cases (0.7 per 1000 deliveries) No maternal deaths occurred, but there were
      2 early neonatal deaths (6.1 %). Atony of the uterus was the main cause of
      hemorrhage (n=15). Genital tract laceration was associated with a worse
      prognosis, but the time lapse between delivery and surgery appears to be the main
      prognostic factor. CONCLUSION: Uterine atony and morbid adherent placenta are
      major causes of massive obstetric hemorrhage. In our series, morbidity was high,
      but there was no mortality. Obstetricians should identify women at risk which is
      especially associated with a prior cesarean delivery, a current placenta previa
      and high parity. Early intervention and proper procedure could minimize the
      complications.

PMID- 16985302
TI  - Empyema of the gall bladder: reappraisal in the laparoscopy era.
AB  - BACKGROUND: In evaluations of laparoscopic cholecystectomy for acute
      cholecystitis, the role of this technique specifically for empyema of the gall
      bladder has not been separately addressed. Therefore, we describe the demographic
      characteristics, clinical and laboratory findings, management and outcome of
      patients presenting with empyema of the gall bladder who were treated with open
      cholecystectomy or laparoscopic cholecystectomy. PATIENTS AND METHODS: Our
      retrospective evaluation included 1449 patients who underwent cholecystectomy
      over 88 months, including a 30-month period when open cholecystectomy was the
      standard operation and a 58-month period when laparoscopic cholecystectomy became
      the standard operation for acute and chronic cholecystitis. RESULTS: Of the 1449
      cholecystectomies, 29 cases proved to have empyema, an incidence of 2%. Males
      constituted 48.3% of the patients (vs. 22% for the whole cholecystectomy group, P
      < or = 0.005) and the average age was 54.6 years (vs. 43 years for the whole
      cholecystectomy group, P < or = 0.005). The clinical picture was
      indistinguishable from other forms of acute cholecystitis. Laparoscopic
      cholecystectomy was attempted for all the patients in the laparoscopy era with a
      conversion rate of 42%, significantly higher than other forms of gall bladder
      diseases (P=0.002). CONCLUSION: Empyema of the gall bladder is more often
      encountered in males and the elderly. The clinical picture is indistinguishable
      from other forms of acute cholecystitis and a preoperative diagnosis is
      difficult. Early laparoscopic cholecystectomy is advisable for all patients with
      acute cholecystitis. A higher conversion rate is expected for patients with
      empyema.

PMID- 16985303
TI  - Prevalence of resistance to antituberculosis drugs in Riyadh and a review of
      previous reports.
AB  - BACKGROUND: Resistance to antituberculosis drugs is an important cause of
      treatment failure. We evaluated the prevalence and pattern of antituberculosis
      drug resistance in the central region of Saudi Arabia, and reviewed previous
      reports from Saudi Arabia. MATERIALS AND METHODS: We retrospectively examined the
      records of sputum smear and culture-positive pulmonary tuberculosis patients
      admitted consecutively from 1998 through 1999 in a main referral hospital in
      Riyadh, and analyzed drug sensitivity reports. We also reviewed previous reports
      on antituberculosis drug resistance in Saudi Arabia. RESULTS: Of 515 patients
      with pulmonary tuberculosis, 80 (15.5%) had resistance to at least one
      antituberculosis drug. Resistance to streptomycin was most frequent (9.7% ),
      followed by rifampicin (9.5%), isoniazid (4.3%), and ethambutol (0.2%).
      Resistance to one antituberculosis drug was found in 8.9%, resistance to two
      drugs in 5.2%, resistance to three drugs in 1.2%, and resistance to four drugs in
      0.2%. Multidrug resistance (defined as resistance to at least isoniazid and
      rifampicin) was found in 1.9% of patients. A literature review including 6114
      patients in Saudi Arabia showed that resistance against streptomycin was most
      common (8.8%), followed by rifampicin (8%), and isoniazid (7.2%). Of the 6114
      patients, 6.8% patients were resistant to only one drug, 3.6% were resistant to
      two drugs, and 3.7% to three drugs. CONCLUSION: The high prevalence of rifampicin
      resistance and resistance to multiple drugs in the Riyadh region and in other
      parts of Saudi Arabia is a major challenge to the control of tuberculosis in this
      country. Efforts should be made to prevent the emergence of further
      antituberculosis drug resistance.

PMID- 16985304
TI  - Quality assurance study for dosimetry of radiation therapy equipment in Saudi
      Arabia.
AB  - BACKGROUND: International standards address the accuracy of dose delivery for
      radiation therapy machines as well as quality assurance and staffing levels for
      radiation therapy centers. We performed absolute calibrations of gamma, x-ray and
      electron radiotherapy beams in all radiation therapy centers in Saudi Arabia. We
      also assessed quality assurance and staffing levels. MATERIALS AND METHODS:
      Dosimetric measurements were made with a portable dosimetry system, which
      consisted of a calibrated Farmer ionization chamber and an electrometer, small
      water phantom, barometer, and thermometer. RESULTS: Differences between the
      measured and the expected output (cGy/MU or cGy/min) were found to be in the
      range of -11% + 5%. About 17% of the radiotherapy beams were not within the
      acceptable tolerance level (+/-3%). Quality assurance in some radiation therapy
      centers was poor and staffing levels were inadequate. CONCLUSIONS AND
      RECOMMENDATIONS: We found poor compliance with internationally accepted tolerance
      levels for dose calibration of radiotherapy beams at radiation therapy centers in
      Saudi Arabia. Analysis of medical physics staffing revealed severe discrepancies
      from those recommended by international guidelines. We recommend that radiation
      therapy centers be adequately staffed with qualified medical physics personnel
      and that periodic audit programs be required by a governmental body.

PMID- 16985305
TI  - Erythrocyte membrane proteins in healthy Saudis and patients with hereditary
      spherocytosis and hereditary elliptocytosis.
AB  - BACKGROUND: Little is known about hereditary spherocytosis (HS) and hereditary
      elliptocytosis (HE) in the native population of Saudi Arabia, even though these
      conditions are seemingly common. The purpose of this study was to ascertain the
      protein make-up of the red cell membrane in healthy Saudis and in patients with
      HS and HE. PATIENTS AND METHODS: Eighteen healthy Saudi subjects (13 males and 5
      females), 11 patients with HS (6 males and 5 females) and 11 patients with HE (7
      males and 4 females) were studied. All normal controls and patients underwent SDS
      PAGE red cell membrane protein analysis in duplicate and the stained protein
      bands were identified and quantitated by densitometry. RESULTS: In normal,
      healthy Saudis, the mean values for seven membrane proteins ( I+/- spectrin, I(2)
      spectrin, ankyrin, band 3, protein 4.1, protein 4.2, and actin) were similar to
      those published for normal, healthy Americans. Of the eleven cases with HS, 7
      (64%) demonstrated detectable protein abnormalities while 4 (36%) were apparently
      normal. The electrophoretic patterns of membrane proteins in Saudis with HS
      differed from those of patients with HS in other parts of the world. Of the 11
      cases of HE, 7 (64%) displayed abnormalities while 4 (36%) were normal.
      CONCLUSION: The electrophoretic pattern of the main proteins in the membranes of
      red blood cells in healthy Saudis is similar to that reported from the USA.
      However, significant differences exist in the electrophoretic patterns between
      Saudi patients with HS and patients from other parts of the world.

PMID- 16985306
TI  - Accuracy of the "triple test" in the diagnosis of palpable breast masses in Saudi
      females.
AB  - BACKGROUND: For patients who present to clinicians with palpable breast lesions,
      the triple test: (physical examination, mammography and fine-needle aspiration
      cytology) can be employed to provide accurate diagnosis. In this study, the
      sensitivity, specificity and predictive values of triple test components were
      studied separately and in combination. MATERIAL AND METHODS: During the study
      period (from January 1998 to December 1999), 140 patients with palpable breast
      masses were subjected to all components of the triple test followed by
      confirmatory open biopsy. RESULTS: Physical examination showed 82.6% sensitivity,
      97.3% specificity and 86.4% positive predictive value. Mammography showed 87.5%
      sensitivity, 97.3% specificity and 87.5% positive predictive value and fine
      needle aspiration cytology (FNAC) showed 91.7% sensitivity, 100% specificity and
      100% positive predictive value in concordant cases (elements had either all
      malignant or all benign results). CONCLUSION: The triple test was 100% accurate
      in the diagnosis of palpable breast lesions when all three elements were
      concordant. Based on these results, we recommend elimination of the confirmatory
      open biopsy, which will result in reduced expenses and morbidity compared with
      open biopsy.

PMID- 16985308
TI  - Leukoencephalopathy and cortical laminar necrosis associated with intrathecal
      methotrexate and cranial irradiation.

PMID- 16985307
TI  - Baseline population survey data on the prevalence of risk factors for coronary
      artery disease among Kuwaitis aged 15 years and older.
AB  - BACKGROUND: There are no baseline population survey data on the prevalence of
      risk factors for coronary artery disease (CAD) among normal, healthy Kuwaiti
      women upon which future interventional studies can be based. SUBJECTS AND
      METHODS: We collected data on the prevalence of excessive weight, obesity,
      diabetes mellitus, dyslipidemia, current smoking and physical inactivity for
      7,609 apparently healthy Kuwaitis aged 15 years and older by means of a household
      survey. Using a structured questionnaire, we collected demographic data from the
      respondents, measured their body weight and height, and collected blood samples
      for measurement of glucose, total cholesterol, high-density lipoprotein
      cholesterol (HDL-C), triglycerides, and apolipoproteins A1 and B. RESULTS: The
      prevalence of obesity among adult Kuwaitis was 23.5%. It was higher among women
      (30.0%) than among men (17.5%). The combined prevalence of obesity and excessive
      weight in the population was 58% (63.4% among women and 53% among men). Diabetes
      mellitus and hypercholesterolemia were slightly higher in women than in men (21.8
      vs 17.7 and 36.6 vs 30.2% respectively) while hypertriglyceridemia and low HDL-C
      were higher in men than in women (44.1 vs 33.8 and 52.2 vs 21.8% respectively).
      The prevalence of smoking was significantly higher in men (31.7%) than in women
      (1.4%), while the prevalence of physical inactivity was higher in women (71.4%)
      than in men (50.6%). CONCLUSION: We conclude that Kuwaiti women, like men, have
      high risk factors for CAD and should receive equal attention in future programs
      to prevent CAD death among Kuwaitis.

PMID- 16985309
TI  - Septic shock with skin ulceration and infection after use of a synthetic hip
      spica cast for treatment of congenital dislocation of the hip.

PMID- 16985310
TI  - Hypertriglyceridemia and hypercholesterolemia induced by L-asparaginase.

PMID- 16985311
TI  - Bloody nipple discharge in a 4-year old child.

PMID- 16985312
TI  - Spontaneous rupture of the uterine artery in a non-pregnant woman.

PMID- 16985313
TI  - Spinal cord compression as an initial symptom in childhood acute lymphoblastic
      leukemia: rapid decompression with high dose dexamethasone and chemotherapy
      alone.

PMID- 16985314
TI  - Multi-focal extra-uterine endometrial stromal sarcoma (ESS): a very rare
      complication of endometriosis associated with elevated serum CA-125.

PMID- 16985315
TI  - Pseudomyxoma peritonei due to intrauterine perforation of a volvulus.

PMID- 16985316
TI  - Acute appendicitis in infants: still a diagnostic dilemma.

PMID- 16985317
TI  - Pulmonary interstitial emphysema in a full-term infant: do we know the incidence?

PMID- 16985318
TI  - Cowper's syringocele (cyst of the bulbar urethra): a case report and literature
      review.

PMID- 16985319
TI  - Repair of an extensive tear of the unscarred uterus resulting from spontaneous
      rupture.

PMID- 16985320
TI  - Crohn's colitis in infancy.

PMID- 16985321
TI  - Urolithiasis in the pediatric age group.

PMID- 16985322
TI  - Clinical profile and outcome of poisoning in Najran.

PMID- 16985324
TI  - Spectral analysis of heart rate variability in diabetic patients: a study of 20
      cases from King Abdulaziz University Hospital.

PMID- 16985323
TI  - Expression of cathepsin D in colorectal adenocarcinomas: correlation with
      clinicopathologic features.

PMID- 16985325
TI  - Appendiceal spirochetosis: a light and electron microscope study of two cases.

PMID- 16985326
TI  - Pattern of breastfeeding of preterm infants in hospitals and after discharge.

PMID- 16985327
TI  - Effect of Ramadan fasting on clinical and biochemical parameters in healthy
      adults.

PMID- 16985331
TI  - Wound infection in cardiac surgery.

PMID- 16985332
TI  - Recurrence of thrombocytopenia in previously diagnosed thrombotic
      thrombocytopenia purpura (TTP) does not always mean TTP recurrence.

PMID- 16985334
TI  - Experience with cervical pap smears at the University Hospital in Jeddah.

PMID- 16985335
TI  - Congenital anomalies of the kidneys in family members.

PMID- 16985336
TI  - Medical curricula in Saudi Medical Colleges.

PMID- 16985337
TI  - Hepatitis B serum markers among pregnant women in Sana'a, Yemen.

PMID- 16985338
TI  - Helping meet the challenges facing academic medicine.

PMID- 16985340
TI  - Regional solutions to the physician workforce shortage: the WWAMI experience.
AB  - With major medical organizations predicting a national shortage of physicians in
      coming years, a number of institutional models are being considered to increase
      the numbers of medical students. At a time when the cost of building new medical
      schools is extremely expensive, many medical schools are considering alternative
      methods for expansion. One method is regional expansion. The University of
      Washington School of Medicine (UWSOM) has used regional expansion to extend
      medical education across five states without the need to build new medical
      schools or campuses. The WWAMI program (the acronym for Washington, Wyoming,
      Alaska, Montana, Idaho), which was developed in the early 1970s, uses existing
      state universities in five states for first-year education, the Seattle campus
      for second-year education, and clinical sites across all five states for clinical
      education. Advantages of regional expansion include increasing enrollment in a
      cost-effective fashion, increasing clinical training opportunities, responding to
      health care needs of surrounding regions and underserved populations, and
      providing new opportunities for community-based physicians to enhance their
      practice satisfaction. Challenges include finding basic-science faculty at
      regional sites with backgrounds appropriate to medical students, achieving
      educational equivalence across sites, and initiating new research programs.
      UWSOM's successful long-term regional development, recent expansion to Wyoming in
      1997, and current consideration of adding a first-year site in Spokane,
      Washington, indicate that regional expansion is a viable option for expanding
      medical education.

PMID- 16985341
TI  - Meeting the needs of regional minority groups: the University of Washington's
      programs to increase the American Indian and Alaskan native physician workforce.
AB  - Minority populations in the United States are growing rapidly, but physician
      workforce diversity has not kept pace with the needs of underserved communities.
      Minorities comprised 26.4% of the population in 1995; by 2050, these groups will
      comprise nearly half. Medical schools must enlist greater numbers of minority
      physicians and train all physicians to provide culturally responsive care. The
      University of Washington School of Medicine (UWSOM) is the nation's only medical
      school that serves a five-state region (Washington, Wyoming, Alaska, Montana, and
      Idaho). Its mission addresses the need to serve the region, rectify primary care
      shortages, and meet increasing regional demands for underserved populations. The
      UWSOM Native American Center of Excellence (NACOE) was established as one
      important way to respond to this charge. The authors describe pipeline and
      minority recruitment programs at UWSOM, focusing on the NACOE and other
      activities to recruit American Indian/Alaskan Native (AI/AN) applicants to
      medical schools. These programs have increased the numbers of AI/AN medical
      students; developed the Indian Health Pathway; worked to prepare students to
      provide culturally responsive care for AI/AN communities; researched health
      disparities specific to AI/AN populations; provided retention programs and
      services to ensure successful completion of medical training; developed
      mentorship networks; and provided faculty-development programs to increase entry
      of AI/AN physicians into academia. Challenges lie ahead. Barriers to the pipeline
      will continue to plague students, and inadequate federal funding will have a
      significant and negative impact on achieving needed physician-workforce
      diversity. Medical schools must play a larger role in resolving these, and
      continue to provide pipeline programs, retention programs, and minority faculty
      development that can make a difference.

PMID- 16985345
TI  - The evolution of a required research program for medical students at the
      University of Washington School of Medicine.
AB  - The concepts and tools clinicians use to understand disease and treat patients
      are the direct product of basic and applied scientific inquiry. To prepare
      physicians to participate in this tradition of medical science, the University of
      Washington School of Medicine (UWSOM) created a research requirement in 1981. The
      objective was to provide students, during their clinical years of medical school,
      with first-hand experience in hypothesis-driven inquiry and an understanding of
      the philosophies and methods of science integral to the practice of medicine. A
      comprehensive curriculum review in 1998-2000 identified several limitations of
      this requirement. Although many students completed it successfully, others
      struggled to find mentors, funding, or time as coursework became more demanding.
      Other students found they had no interest in or aptitude for the research process
      itself. Accordingly, UWSOM has reaffirmed its commitment to independent inquiry
      but expanded the ways in which students can meet the requirement. Three research
      options are now available under the Independent Investigative Inquiry (III)
      program, generally completed the summer after students' first year of medical
      school. These are the hypothesis-driven inquiry, a critical review of the
      literature, or an experience-driven inquiry in community medicine. The goal of
      UWSOM is to shape new physicians who can manage rapidly changing medical science,
      information technology, and patient expectations in clinical practice and/or
      laboratories. The role of III is to teach students to develop personal methods of
      acquiring new knowledge and integrate it into their professional lives. Faculty
      support, program oversight, and funding have been increased.

PMID- 16985343
TI  - Professionalism in medical education: an institutional challenge.
AB  - Despite considerable attention to professionalism in medical education
      nationwide, the majority of attention has focused on training medical students,
      and less on residents and faculty. Curricular formats are often didactic, removed
      from the clinical setting, and frequently focus on abstract concepts. As a result
      of a recent curricular innovation at the University of Washington School of
      Medicine (UWSOM) in which role-model faculty work with medical students in
      teaching and modeling clinical skills and professionalism, a new professionalism
      curriculum was developed for preclinical medical students. Through student
      feedback, that curriculum has changed over time, and has become more focused on
      the clinical encounter. This new and evolving curriculum has raised awareness of
      the existence of an "ecology of professionalism." In this ecological model,
      changes in the understanding of and attention to professionalism at one
      institutional level lead to changes at other levels. At the UWSOM, heightened
      attention to professionalism at the medical student level led to awareness of the
      need for increased attention to teaching and modeling professionalism among
      faculty, residents, and staff. This new understanding of professionalism as an
      institutional responsibility has helped UWSOM teachers and administrators
      recognize and promote mechanisms that create a "safe" environment for fostering
      professionalism. In such an institutional culture, students, residents, faculty,
      staff, and the institution itself are all held accountable for professional
      behavior, and improvement must be addressed at all levels.

PMID- 16985346
TI  - HIPAA or hippocrates on the phone?

PMID- 16985347
TI  - Positioning a medical school for modern biomedical research: the department of
      genome sciences at the University of Washington School of Medicine.
AB  - The availability of genome sequences from a multitude of organisms, which began
      about a decade ago, has had enormous impact throughout the biomedical sciences.
      These sequence data have changed the way research studies are carried out and
      have led to the explosive growth of computational biology as an approach to
      analyze biological processes and evolution. In medicine, the completion of the
      human genome sequence has illuminated the function of many genes, facilitated the
      correlation of mutant genes to disease phenotypes, and provided a basis for the
      study of human variation. At the University of Washington, the two academic
      departments whose overall programs were most centrally affected by the sequencing
      revolution were Genetics and Molecular Biotechnology. These departments were
      fused in 2001 to form the Department of Genome Sciences in order to best exploit
      these developments and to become a prototype for the basic biomedical science
      department of the future. The department's goal is to address leading-edge
      questions in biology and medicine through the application of genetics, genomics,
      proteomics, and computational approaches to the increasing collection of known
      genome sequences and their encoded products. The authors review the events that
      led up to the founding of this department and discuss the initiatives that have
      been undertaken, which include the recruitment of faculty, the establishment of a
      new interdisciplinary graduate program, the continued development of an outreach
      program, and the construction of a building to house the department. Lessons
      learned in crafting this department are also discussed, as well as how these
      might apply to other medical schools.

PMID- 16985348
TI  - The public hospital mission at Seattle's Harborview Medical Center: high-quality
      care for the underserved and excellence in medical education.
AB  - United States public hospitals and medical schools commonly enter into
      partnerships that serve the patient care, education, and research missions of
      both institutions. Harborview Medical Center, the county hospital in Seattle,
      Washington, and the University of Washington School of Medicine (UWSOM) have
      enjoyed a long affiliation that began at the medical school's founding 60 years
      ago. A formal agreement in 1967 turned over responsibility for all Harborview
      operations to UWSOM at a time when Harborview's facilities had fallen into
      serious disrepair and public hospitals were closing across the United States. All
      faculty and staff based at Harborview are employed by the University of
      Washington. By the mid-1970s a revitalization was underway at Harborview. The
      Medic One paramedic program drew national acclaim for pioneering prehospital
      emergency cardiac care, and the trauma and burn centers grew rapidly to meet
      specialized intensive care needs of the Pacific Northwest. Today, the success of
      the trauma, specialty surgery, and rehabilitation services have allowed
      Harborview to consistently maintain a positive operating margin while caring for
      the county's uninsured and indigent patients ($98 million in charity care in
      2005). The hospital also offers nationally recognized residency programs and
      supports nationally and internationally acclaimed research. Harborview faces
      significant challenges for the future, including rapid growth of the indigent
      patient load, continually changing expectations for physician training, and
      growing cost pressures.

PMID- 16985349
TI  - Working across the boundaries of health professions disciplines in education,
      research, and service: the University of Washington experience.
AB  - The Institute of Medicine's vision for health professions education specifies
      working together across professions and schools to provide patient-centered care.
      Improvement in collaborative preparation of health professionals is seen as
      central to achieving substantial improvement in the quality of health care. In
      this article, the authors address one central question: How can medical schools
      work with other health-sciences schools to promote their educational, research,
      and service missions? The authors summarize the history of the University of
      Washington (UW) Health Sciences Center in promoting interprofessional
      collaboration in education, service and research; analyze the key strategic,
      structural, cultural and technical elements that have promoted success or served
      as barriers in the development of the UW Center for Health Sciences
      Interprofessional Education and Research; and suggest strategies that may be
      transferable to other institutions seeking to implement an interprofessional
      health sciences program. These include both top-down and bottom-up authority and
      function in key working groups, institutional policies such as interprofessional
      course numbers and shared indirect costs, and development of a culture of
      interprofessionalism among faculty and students across program boundaries.

PMID- 16985351
TI  - Addressing global health through the marriage of public health and medicine:
      developing the University of Washington department of global health.
AB  - Widespread interest in global health issues is a common characteristic of
      students and faculty in schools of public health and schools of medicine.
      Building on strong university-based and community-based programs in global
      health, the University of Washington has created a unique Department of Global
      Health that is housed jointly in its School of Public Health and Community
      Medicine and its School of Medicine. The creation of this department has
      generated significant enthusiasm throughout the university and the Seattle
      community as a new paradigm for addressing global health education, research, and
      service. Placing the new Department of Global Health in two university schools
      and finding the appropriate niche for the department among the university's many
      global health initiatives presented challenges, as well as opportunities. This
      article describes the goals of the department, the process by which it was
      created, and what it expects to accomplish.

PMID- 16985355
TI  - Viewpoint: the elephant in medical professionalism's kitchen.
AB  - The rise of the corporation within health care during the 1980s and early 1990s
      was met by organized medicine with a deluge of editorials, articles, and books
      that identified a singular enemy--commercialism--and depicted it as corrosive of,
      and antithetical to, medical professionalism. Medicine's ire proved prognostic as
      scores of highly publicized corporate-medical scandals began to crater the
      landscape of a rapidly emerging "medical marketplace." Medicine's main weapon in
      this counteroffensive was a renewed call to medical professionalism. Numerous
      organizations hosted conferences and underwrote initiatives to define, measure,
      and ultimately inculcate professionalism as a core medical competency.
      Nonetheless, an examination of medicine's overall response to the threat of
      commercialism reveals inconsistencies and schisms between these praiseworthy
      efforts and a parallel absence of action at the community practitioner and peer
      review levels. The most recent salvo in this war on commercialism is a policy
      proposal by influential medical leaders who call for an end to the market
      incentives linking academic health centers and medical schools with industry.
      These forthright proposals nevertheless appear once again not to address the
      heartbeat of professional social control: community-based peer review, including
      a vigorous and proactive role by state medical boards. The author concludes by
      examining the implications of a professionalism bereft of peer review and
      explores the societal-level responsibilities of organized medicine to protect,
      nurture, and expand the role of the physician to maintain the values and ideals
      of professionalism against the countervailing social forces of the free market
      and bureaucracy.

PMID- 16985356
TI  - What's in a name?

PMID- 16985358
TI  - The human face of simulation: patient-focused simulation training.
AB  - Simulation is firmly established within health care training but often focuses on
      training for technical tasks and can overlook crucial skills such as
      professionalism and physician-patient communication. The authors locate this
      paper within current developments in health care and relate it to the literature
      on simulation. They make the case for placing real human "patients" (played by
      actors) within simulation environments, thereby ensuring that the training
      experience remains rooted in actual practice. By practicing repeatedly within a
      safe environment, technical skills, communication with patients and team members,
      decision making, and clinical judgment may all be practiced and mastered while
      preserving patient safety. In elaborating this concept of patient-focused
      simulation (PFS), the authors draw on work already published by their group and
      several recent studies that are in review. These explore PFS in low, medium, and
      high complexity settings. Important or rare situations can be recreated and
      practiced, as well as key procedures required across a range of experience levels
      and clinical specialties. Finally, the case is made for curriculum redesign to
      ensure that simulator-based technical skills training and assessment take place
      within an authentic context that reflects the wider elements of clinical
      practice.

PMID- 16985357
TI  - Competence and cognitive difficulty in physicians: a follow-up study.
AB  - PURPOSE: Remediation of incompetent physicians has proven difficult and sometimes
      impossible. The authors wished to determine whether such physicians had
      neuropsychological impairment sufficient to explain their incompetence and their
      failure to improve after remedial continuing medical education (CME). METHOD:
      Between 1997 and 2001, the authors undertook neuropsychological screening of 45
      participants of a physician competency assessment program. For those physicians
      reassessed after a period of remediation, the authors relate the findings of the
      physicians' competence reassessments to their neuropsychological scores. RESULTS:
      Nearly all physicians performing well on competency assessment had no or mild
      cognitive impairment. Conversely, a significant number of physicians performing
      poorly on competency assessment had sufficient neuropsychological difficulty to
      explain their poor performance. The cognitive impairment was more marked in
      elderly physicians, and referencing the neuropsychological scores to an age
      matched normative population underestimates the impairment. No physician with
      moderate or severe neuropsychological dysfunction had successful competency
      reassessment. Increasing age was associated with poor performance on competency
      testing, but was less strongly associated with unsuccessful reassessment.
      CONCLUSION: A large minority of the physicians who fell significantly below
      desired levels of competence had cognitive impairment sufficient to explain their
      lack of competence and their failure to improve with remedial CME.

PMID- 16985359
TI  - Using a web-based, iterative education model to enhance clinical clerkships.
AB  - Although most clinical clerkship curricula are designed to provide all students
      consistent exposure to defined course objectives, it is clear that individual
      students are diverse in their backgrounds and baseline knowledge. Ideally, the
      learning process should be individualized towards the strengths and weakness of
      each student, but, until recently, this has proved prohibitively time-consuming.
      The authors describe a program to develop and evaluate an iterative, Web-based
      educational model assessing medical students' knowledge deficits and allowing
      targeted teaching shortly after their identification. Beginning in 2002, a new
      educational model was created, validated, and applied in a prospective fashion to
      medical students during an internal medicine clerkship at Harvard Medical School.
      Using a Web-based platform, five validated questions were delivered weekly and a
      specific knowledge deficiency identified. Teaching targeted to the deficiency was
      provided to an intervention cohort of five to seven students in each clerkship,
      though not to controls (the remaining 7-10 students). Effectiveness of this model
      was assessed by performance on the following week's posttest question. Specific
      deficiencies were readily identified weekly using this model. Throughout the
      year, however, deficiencies varied unpredictably. Teaching targeted to
      deficiencies resulted in significantly better performance on follow-up
      questioning compared to the performance of those who did not receive this
      intervention. This model was easily applied in an additive fashion to the current
      curriculum, and student acceptance was high. The authors conclude that a Web
      based, iterative assessment model can effectively target specific curricular
      needs unique to each group; focus teaching in a rapid, formative, and highly
      efficient manner; and may improve the efficiency of traditional clerkship
      teaching.

PMID- 16985361
TI  - Successful internal mammary visualization with periareolar injections of Tc-99m
      antimony sulfur colloid in sentinel node breast lymphoscintigraphy.
AB  - PURPOSE: The subareolar and periareolar injection techniques result in higher
      detection rates and do not require tumor localization in impalpable lesions when
      compared with the peritumoral technique. One of the main criticisms, however, is
      the widely reported inability to detect internal mammary nodes. This contrasts
      with our clinical experience using Tc-99m antimony sulfur colloid, in which
      internal mammary nodes are commonly seen. METHODS: A retrospective analysis of
      241 patients over 38 months was performed to investigate the ability of our
      periareolar injection technique to detect internal mammary lymph node drainage in
      breast cancer sentinel node lymphoscintigraphy. Four injections of 5 to 10 MBq
      (0.14-0.27 mCi) Tc-99m antimony sulfur colloid were administered on the day of
      surgery followed by massage and imaging. The radioisotope was suspended in 0.1 mL
      with a 0.5-mL air lock. Each injection was performed over 2 seconds with a 25
      gauge needle at a depth of 1.1 to 1.3 cm. Patients whose records could not be
      retrieved or who underwent an injection technique apart from periareolar or
      peritumoral were removed from the analysis. RESULTS: One hundred thirty-three
      patients underwent the periareolar technique, 72 patients underwent the
      peritumoral technique, and 36 patients were excluded from the analysis. Internal
      mammary drainage was seen in 24 of 133 (18.0%) patients, of which 12 (9%) were
      seen only in the internal mammary chain. This is much higher than previous
      studies quoting 0.0% to 4.3% and is similar to previously reported rates using
      the peritumoral technique. CONCLUSIONS: Our periareolar injection technique using
      Tc-99m antimony sulfur colloid is able to detect internal mammary lymph nodes in
      at least 18.0% of patients.

PMID- 16985362
TI  - Uncommon findings in Tc-99m macroaggregated albumin venography in distal inferior
      vena cava obstruction.
AB  - In inferior vena cava obstruction, collateral pathways allow the retrograde flow
      of venous blood from the lower part of the body. Unanticipated findings of Tc-99m
      macroaggregated albumin (MAA) venography in 3 cases with deep vein thrombosis of
      the legs and infrarenal inferior vena cava obstruction are presented. Apart from
      extensive collateral networks in the legs and the abdomen, the visualization of
      the liver indicates a shunt of the systemic venous blood flow through the
      paraumbilical vein to the portal vein. The visualization of lumbar and thoracic
      vertebrae is attributed to venous flow through a dilated vertebral plexus,
      resulting in trapping of tracer in the neighboring bone marrow.

PMID- 16985363
TI  - The scintigraphic appearance of de Quervain tenosynovitis.
AB  - PURPOSE: The purpose of this study is to describe the scintigraphic pattern of de
      Quervain tenosynovitis, a common inflammatory condition of the thumb tendon
      sheaths related to repetitive use. MATERIALS AND METHODS: The author conducted a
      retrospective audit of consecutive cases with independent clinical validation of
      the final diagnosis. RESULTS: There were 7 cases of clinically confirmed de
      Quervain tenosynovitis. The typical scintigraphic finding was a focal area of
      superficial linear hyperemia and skeletal uptake along the radial aspect of the
      distal radius corresponding to the anatomic location of the abductor pollicis
      longus and extensor pollicis brevis. All cases showed an abnormality on at least
      one phase of the bone scan. CONCLUSIONS: Bone scanning appears to be of value in
      the differential diagnosis of dorsolateral wrist pain when clinical findings are
      nondiagnostic. The scintigraphic appearance of de Quervain tenosynovitis can help
      to confirm the diagnosis while excluding other causes of wrist pain. Determining
      the sensitivity and specificity of this pattern will require further research.

PMID- 16985364
TI  - Clinical role of Sm-153 EDTMP in the treatment of painful bone metastatic
      disease.
AB  - PURPOSE: Sm-153 EDTMP is an effective treatment of painful bone metastases from
      different neoplasms. However, there are few studies describing clinical
      experience with this therapeutic modality. The aim of this clinical study was to
      evaluate the efficacy of Sm-153 EDTMP in a group of patients with skeletal
      metastases and poor pain control with conventional therapies. MATERIALS AND
      METHODS: Sixty-four patients with painful bone metastases treated with Sm-153
      EDTMP were retrospectively evaluated. Nine patients were treated twice. The most
      common primaries were breast in 28 cases (44%) and prostate in 27 (41%).
      Treatment efficacy was assessed by a visual analog scale, analgesic consumption,
      and performance status before and after treatment. Response was graded as
      complete, moderate, or minor. Toxicity evaluation included analytic parameters
      (blood counts, renal function) and clinical follow up. RESULTS: Efficacy and
      toxicity were evaluated separately for each dose (total doses: 73), and complete
      follow up was only possible in 62 of 73 administrations. The response rate was
      85% (21% complete, 40% moderate, and 24% minor). Onset of improvement took place
      a median of 7 days after Sm-153 EDTMP administration, and pain relief persisted
      for a mean of 3 months. No relevant toxicity was found in the early phase.
      Myelotoxicity appeared in 29% of the administrations and was mild in most cases
      (there was one case of grade 4 leukopenia). CONCLUSIONS: Sm-153 EDTMP is a good
      therapeutic option for patients with painful bone metastases. It is an effective
      treatment of pain relief without major secondary effects.

PMID- 16985365
TI  - Visualization of hepatic metastases of medullary thyroid carcinoma on Tc-99m MDP
      bone scintigraphy.
AB  - A 35-year-old man with a history of medullary carcinoma of the thyroid underwent
      a whole-body bone scan for chest wall pain. Extensive irregular radionuclide
      uptake was observed in hepatic metastases in both lobes, later confirmed on CT
      scan. A case of technetium-99m MDP uptake in hepatic metastases from medullary
      carcinoma of the thyroid is presented and the literature is reviewed.

PMID- 16985366
TI  - Imaging of an invasive malignant thymoma on PET Scan: CT and histopathologic
      correlation.
AB  - Thymomas are common primary mediastinal neoplasms. They can be benign or
      malignant. The diagnosis of malignant thymomas is based on capsular invasion,
      cellular atypia and distant metastases. We present a case of invasive malignant
      thymoma as diagnosed on PET and CT scan with histologic correlation and review of
      literature. A seventy year old Asian man presented with cough and dyspnea. A CT
      scan showed an anterior mediastinal mass, and a PET scan showed a hypermetabolic
      mass in the corresponding location. Resection of the mass revealed a minimally
      invasive thymoma based on evidence of capsular invasion. PET scan proved
      invaluable in correctly diagnosing, staging the lesion, and excluding any
      extramediastinal involvement.

PMID- 16985367
TI  - Transformed non-hodgkin lymphoma demonstrated on thallium-201 and gallium-67
      scintigraphy.

PMID- 16985368
TI  - Pseudoaneurysm mimicking a soft tissue sarcoma.

PMID- 16985369
TI  - Hepatobiliary scintigraphy monitoring patency of partial external biliary
      diversion in a patient with progressive familial intrahepatic cholestasis.

PMID- 16985370
TI  - Pulmonary hypertrophic osteoarthropathy in a patient with nonsmall cell lung
      cancer: Diagnosis with FDG PET/CT.

PMID- 16985371
TI  - F-18 fluorodeoxyglucose positron emission tomography finding of Mazabraud
      syndrome.

PMID- 16985373
TI  - Adult medulloblastoma relapse visualized by in-111 octreotide scintigraphy.

PMID- 16985372
TI  - Urothelial nodal metastasis with direct vertebral invasion: PET/CT imaging.

PMID- 16985374
TI  - False-positive Tl-201 SPECT in a case of cerebral tuberculoma.

PMID- 16985375
TI  - Extraordinarily high F-18 FDG uptake caused by a pleomorphic adenoma of the
      parotid gland.

PMID- 16985376
TI  - Multiple brown tumors with Tc-99m MDP superscan appearance and negative Tc-99m
      MIBI uptake.

PMID- 16985377
TI  - Schwannoma mimicking lung cancer metastases demonstrated by PET/CT.

PMID- 16985378
TI  - Actinomycosis mimicking anastomotic recurrent esophageal cancer on PET-CT.

PMID- 16985379
TI  - Coexisting hyperparathyroidism and oncogenic osteomalacia: Sestamibi and
      somatostatin receptor scintigraphy.

PMID- 16985380
TI  - In-111 DTPA-D-Phe1-octreotide SPECT in a rare case of anorectal small-cell
      undifferentiated neuroendocrine carcinoma.

PMID- 16985381
TI  - Accumulation of Tc-99m MDP by omental tumor in metastatic cecal cancer.

PMID- 16985382
TI  - Current readings in nuclear medicine.

PMID- 16985384
TI  - State Children's Health Insurance Program financing and the need for significant
      federal funding increases as part of reauthorization.
AB  - In order to better inform the debate as federal policymakers prepare to
      reauthorize the State Children's Health Insurance Program (SCHIP) in 2007, this
      brief analyzes the key components of the financing structure of SCHIP including
      capped federal block-grant funding, the methodology for determining state's
      allotments of federal funding, the period of availability of allotments, and the
      redistribution of unspent funds. In addition, estimates presented in this brief
      indicate that under Congressional Budget Office baseline assumptions, SCHIP is
      reauthorized but annual SCHIP funding will be permanently frozen at 5.04 billion
      US dollars without any increases for population growth or healthcare inflation.
      As a result, states will suffer an aggregate federal SCHIP funding shortfall of
      10.4 billion US dollars to 12.1 billion US dollars over the 5-year period from
      2008 through 2012, thus placing SCHIP coverage of many low-income children at
      significant risk. As part of SCHIP reauthorization, federal policymakers should
      include substantial increases to SCHIP funding above baseline levels to avert
      these shortfalls.

PMID- 16985385
TI  - Management tools for Medicaid and State Children's Health Insurance Program
      (SCHIP).
AB  - Medicaid and the State Children's Health Insurance Program need analytic tools to
      manage their programs. Drawing upon extensive discussions with experts in states,
      this article describes the state of the art in tool use, making several
      observations: (1) Several states have linked Medicaid/State Children's Health
      Insurance Program administrative data to other data (eg, birth and death records)
      to measure access to care. (2) Several states use managed care encounter data to
      set payment rates. (3) The analysis of pharmacy claims data appears widespread.
      The article also describes "lessons learned" regarding building capacity and
      improving data to support the implementation of management tools.

PMID- 16985386
TI  - Using medical billing data to evaluate chronically ill children over time.
AB  - This study evaluates stability of chronic condition identification in children
      older than 4 years in a health plan billing data using Clinical Risk Groups. A
      total of 31,055 children were continuously enrolled for 4 years; 7.5% (2,334)
      identified with a chronic condition status in year 1, 2002, and another 15.4%
      (4,784) during subsequent years; 63.6% (19,759) were identified as "healthy"
      throughout. The most stable were those identified with a catastrophic health
      condition. The least stable were those with minor and moderate/dominant major
      chronic conditions. Overall, 73.1% (1,706) of the children with chronic
      conditions in year 1 improved in status, and 5.7% (133) progressed to more
      complex conditions.

PMID- 16985387
TI  - Integration of data and management tools into the new york state medicaid managed
      care encounter data system.
AB  - The New York State Department of Health has created a data warehouse to analyze
      and evaluate the Medicaid managed care program. Online query tools and reports,
      grouping tools such as Diagnostic Related Groups, and measurement tools such as
      Health Plan Data and Information Set (HEDIS) measures have been incorporated into
      the data warehouse. Other public health data sets including birth certificate
      data have also been integrated. The result is a powerful data set that can
      analyze information quickly and efficiently, with built-in data intelligence.
      Developed over time, this system can provide states, health insurance companies,
      and health data consortiums a roadmap on how to implement an integrated data
      warehouse solution.

PMID- 16985388
TI  - Wisconsin's recent BadgerCare enrollment decline: how administrative rules can
      set off unanticipated change.
AB  - The State Children's Health Insurance Program (SCHIP) has been intended to
      provide healthcare coverage to that group of children previously caught between
      Medicaid eligibility and adequate access to employer insurance. However, SCHIP
      can be implemented quite differently across the states, potentially affecting
      actual enrollment. We review prior studies that have attempted to dissect how the
      administration of SCHIP impacts enrollment, including a multivariate study by the
      authors that indicates presumptive eligibility, expanded parent coverage, and 12
      month continuous eligibility all contribute to a reduced likelihood of being
      uninsured. We then detail an administrative policy change in one state,
      Wisconsin, that yielded unanticipated and dramatic enrollment fluctuations in its
      SCHIP program, BadgerCare.

PMID- 16985389
TI  - Dissemination of methods and results from the veterans health study: final
      comments and implications for future monitoring strategies within and outside the
      veterans healthcare system.
AB  - The Veterans Health Study (VHS) followed a cohort of patients receiving
      ambulatory care in the Veterans Affairs healthcare system for up to 5 years. One
      of the principal aims of this study was to develop a library of methodologies
      including general and disease-specific health outcome questionnaires for use in
      monitoring the quality of healthcare and for research purposes. The cornerstone
      for this work is the Veterans RAND 36 and 12 Item Health Surveys (VR-36 and VR
      12), a general measure developed in the VHS for measuring the physical and
      psychologic well-being of the patient. A comprehensive set of disease-specific
      assessments has also been developed as part of this study for the purposes of
      monitoring specific chronic conditions more commonly seen in routine ambulatory
      care settings. Since 1996, more than 2 million questionnaires have been
      administered in the VA for quality monitoring purposes, using the VR-36 and VR
      12. Research studies that have used these batteries span randomized clinical
      trials in the VA cooperative studies program and clinical effectiveness research.
      Health assessments using VHS batteries are being disseminated for widespread use
      outside the VA. Chief among the assessments used is the VR-12, which has recently
      been included in the 2006 Health Plan Employer Data and Information Set (HEDIS)
      as part of the Medicare Health Outcomes Survey for monitoring the Medicare
      Advantage Program. The methods and batteries developed in the VHS are in the
      public domain and provide a framework for future patient monitoring using
      standard measures of health.

PMID- 16985390
TI  - A Patient-based severity measure of chronic lung disease: evaluating functional
      health and predicting health services use.
AB  - Prior research has consistently shown that among patients with chronic lung
      disease (CLD), health-related quality of life (HRQOL) is tied more to respiratory
      symptoms than to physiologic measures. However, traditional methods to quantify
      the severity of CLD have been restricted to physiologic measures (eg, FEV1, FVC,
      etc) that are often poor predictors of HRQOL and utilization of health services.
      Using a patient-based measure of symptom severity for CLD developed in the
      Veterans Health Study (VHS), this article evaluated the impact of the severity of
      CLD on patients' self-reported HRQOL and future use of health services. We used
      data from the VHS, a prospective study of patients receiving ambulatory care
      services in 4 Veterans Affairs outpatient clinics in the greater Boston area.
      Three hundred fifty-two (14.5%) patients were identified as having CLD through
      self-report of having a physician's diagnosis of chronic bronchitis, emphysema,
      or asthma, and either using inhaled medications or having a productive cough for
      most days for 3 months. Ordinary least-square regressions were used to ascertain
      the effects of CLD severity on functional health and health services use.
      Compared with peak expiratory flow rate, which explained only 10% and 2%,
      respectively, of the variance in the SF-36 physical component summary (PCS) and
      in future doctor visits, the symptom severity explained 19% and 19%,
      respectively, of the variance in PCS and future doctor visits, after adjusting
      for age, education, and household income. The symptom severity measure is a
      strong predictor of future functional health (at 12 months of the VHS baseline)
      and health services use (within 6 months following the baseline). The study
      findings indicate that our measure of CLD severity is an efficient and easy-to
      use approach that can be readily administered in ambulatory setting. It can be
      used as a case-mix adjustment in evaluating health outcomes and in predicting
      future utilization of health services.

PMID- 16985391
TI  - A multidisciplinary project to improve the quality of cancer pain management in
      Italy: background, methods, and preliminary results.
AB  - Pain afflicts most cancer patients, mainly in the advanced and metastatic phases
      of the disease. Despite the existence of several guidelines for cancer pain
      management that are based on the recommendations by the World Health Organization
      and the availability of effective treatments for 70% to 90% of cases,
      undertreatment is well documented and can involve up to 40% of patients.
      Undertreatment is usually attributed to an incorrect use of opioids for reasons
      often conceptualized in terms of barriers related to healthcare provider,
      patient, family, institution, and society. In Italy, opioid consumption rates are
      among the lowest in Europe despite some of recent efforts to improve the
      analgesic prescription and utilization. In the context of a wide project
      coordinated by the Mario Negri Institute, a non-for-profit private foundation
      located in Milan, Italy, 4 activities were launched: (1) a critical appraisal of
      information available on the Web, with the preparation and publication of a meta
      site to facilitate the use of selected resources; (2) an evaluation of
      prescriptions of analgesic drugs in a cohort of cancer patients using a large
      administrative database; (3) a nationwide outcome research study to assess the
      epidemiology, quality, and effectiveness of different analgesic strategies; and
      (4) a multimodal, community-based intervention based on information, education,
      and training programs to change the knowledge, opinions, and attitude toward
      cancer pain treatment. Activities started in 2005. Some results and outputs are
      already available; others will be ready by the end of 2007.

PMID- 16985392
TI  - Military medical ethics under attack.

PMID- 16985394
TI  - The third National Reports on Healthcare Quality and Disparities in the United
      States: national data for targeting improvements.

PMID- 16985395
TI  - The Magnet Recognition Program: understanding the appraisal process.

PMID- 16985396
TI  - Noise reduction in the hospital setting.

PMID- 16985397
TI  - Collaboration among nurses, advanced practice nurses, and nurse researchers to
      achieve evidence-based practice change.

PMID- 16985398
TI  - A promising technology to reduce social isolation of nursing home residents.

PMID- 16985399
TI  - Missed nursing care: a qualitative study.
AB  - The purpose of this study was to determine nursing care regularly missed on
      medical-surgical units and reasons for missed care. Nine elements of regularly
      missed nursing care (ambulation, turning, delayed or missed feedings, patient
      teaching, discharge planning, emotional support, hygiene, intake and output
      documentation, and surveillance) and 7 themes relative to the reasons for missing
      this care were reported by nursing staff.

PMID- 16985401
TI  - Dance of the call bells: using ethnography to evaluate patient satisfaction with
      quality of care.
AB  - Ethnographic methods can provide insights into patients' perceptions of quality
      of care. We used ethnographic methods to examine problems related to answering
      patient call lights on one inpatient unit in the hospital. Communication through
      call bells consisted of 3 interrelated components. These included answering the
      call bell, communicating the patient's request, and following through with the
      request. Results of this study provided a deeper understanding of the nuances of
      power and control embedded within the issue of patient-caregiver communication
      and empowered unit staff to find solutions to the call bell problem.

PMID- 16985402
TI  - Meeting the Center for Medicare & Medicaid Services requirements for quality
      assessment and performance improvement: a model for hospitals.
AB  - The Quality Assessment and Performance Improvement (QAPI) model seeks to improve
      the structures and processes of delivering healthcare to gain better outcomes in
      patient care. The goal of the model described in this article is to create an
      integrated approach for hospitals to meet the Center for Medicare & Medicaid
      Services (CMS) quality requirements. This article describes the results of this
      data-driven QAPI method via utilization of this model and its processes. The
      Safety without Restraint task force of Swedish Covenant Hospital was created to
      evaluate compliance with CMS restraint standards and identify discrepancies that
      would provide multiple opportunities to improve performance. The use of this
      model provided nurse leaders an opportunity to improve patient care as well as
      meet the CMS requirements for QAPI.

PMID- 16985403
TI  - Prevention and education to decrease patient falls due to syncope.
AB  - This article describes a fall reduction program implemented by the University of
      Wisconsin Medical Foundation in its 50+ clinic sites and departments located
      across 5 counties in Southern Wisconsin. The fall reduction program specifically
      targeted falls due to faints in the clinic setting. To reduce the organization's
      main reason for patient falls, guidelines were developed and mandatory education
      was given to staff working in high-risk areas.

PMID- 16985404
TI  - Impact of a continuing education activity on the quality of telephone
      interventions by nurses in an adult asthma client base.
AB  - The objectives of this study were to evaluate the effect of a continuing
      education activity on the clinical evaluation and advice provided by nurses
      working for a telephone triage service with an asthmatic client base, and to
      measure the number of referrals to Asthma Education Centers (AECs). The results
      suggest a positive impact on the quality of the telephone intervention in the
      short term, but this was not sustained over time. Few patients were referred to
      an AEC.

PMID- 16985405
TI  - Quality of care: a comparison of perceptions of health professionals in clinical
      areas in the United Kingdom and the United States.
AB  - A tool was developed, using the nominal group and Delphi techniques, to explore
      healthcare staff's perceptions of the quality of hospital care provided in the
      United Kingdom compared with a tool from the United States. Similarities were
      identified in many core areas; however, there were several differences between
      the UK and US tools. This article identifies the process and findings and
      discusses possible reasons for similarities and differences between the tools.

PMID- 16985406
TI  - Float pools and resource teams: a review of the literature.
AB  - The use of nursing float pools and resource teams is a strategy used to cope with
      variable or inadequate staffing. Though identified as a solution to staffing
      shortages, there is limited research to support their use. Little is known about
      how resource teams and float pools work, are structured, or their impact. Both
      allow for staffing flexibility; however, only resource teams appear to be
      designed with nurse competency and patient safety in mind.

PMID- 16985407
TI  - Examination of incidents of workplace verbal abuse against nurses.
AB  - The purpose of this research was to examine the incidents of verbal abuse faced
      by nurses in the workplace in the last year. Data were collected from 290
      hospital nurses in Turkey. The study found that the majority of nurses had faced
      verbal abuse (n = 233, 80.3%). The findings from the research confirm the need
      for urgent and continuous plans for addressing verbal abuse in the workplace and
      for adoption of zero tolerance.

PMID- 16985408
TI  - Are patients in Western Turkey contented with healthcare services?: a quality
      assessment study.
AB  - The purpose of this study was to describe service quality as perceived by 1200
      patients who had inpatient treatment at 3 hospitals in Istanbul: university,
      social security administration, and government. Patients were most satisfied with
      the helpful attitudes of personnel during check-in procedures, promptness and
      skill of nurses, overall service provided by physicians, speedy and skilled work
      of personnel in laboratories and X-ray rooms, and hospitals in general.

PMID- 16985410
TI  - Sleep apnea and commercial motor vehicle operators: statement from the joint Task
      Force of the American College of Chest Physicians, American College of
      Occupational and Environmental Medicine, and the National Sleep Foundation.

PMID- 16985411
TI  - VISA Classification for Graves orbitopathy.

PMID- 16985412
TI  - Techniques for upper eyelid loading.

PMID- 16985413
TI  - Changes in corneal topography with upper eyelid gold weight implants.
AB  - PURPOSE: To determine the effect of upper eyelid gold weight implantation on
      corneal astigmatism. METHODS: This is a prospective, cohort study. Eighteen eyes
      of 18 patients underwent upper eyelid gold weight implantation for facial nerve
      palsy. Nine of these patients recovered facial nerve function and underwent
      elective removal of the gold weight. Corneal topography was performed before and
      after gold weight implantation. Corneal topography was also performed after gold
      weight removal in patients who recovered from facial nerve paralysis. RESULTS:
      With-the-rule corneal astigmatism increased significantly by 1.4 diopters (D) +/
      2.0, from a mean of 0.3 to 1.7 D after gold weight implantation (p = 0.034). With
      the-rule corneal astigmatism in patients who had gold weight removal decreased by
      1.2 +/- 2.1 D, from 2.2 to 1.0 D after gold weight removal (p = 0.136).
      CONCLUSIONS: Upper eyelid gold weight implantation causes an increase in corneal
      astigmatism, predominantly in the vertical axis, which appears to be reversible
      on removal of the gold weight.

PMID- 16985414
TI  - Filling the periorbital hollows with hyaluronic acid gel: initial experience with
      244 injections.
AB  - PURPOSE: To review our initial experience using hyaluronic acid gel (Restylane)
      as a filler to treat the periorbital hollows. METHODS: This is a retrospective,
      anecdotal case review of 244 cosmetic hyaluronic acid gel injections in 155
      patients. An average volume of 0.9 ml per injection session was used in an
      individualized pattern that variably included the orbital rim hollow, zygomatic
      hollow, septal confluence hollow, and eyebrow and cheek fat pad. To achieve
      smooth contours, a layered, feathered threading technique was used, placing the
      filler deep to the orbicularis. Hyaluronidase injections were used in 11% of
      patients at follow-up visits to "dissolve" some of the filler to reduce contour
      irregularities. RESULTS: One hundred eight of 121 (89%) patients with follow-up
      visits were satisfied with the cosmetic improvement after hyaluronic acid gel
      injections. For maintenance, the interval to second injection averaged 6.5
      months. Side effects included lumps or contour irregularities (11%), bruising
      (10%), color change (7%), and fluid (15%). Twelve patients were unsatisfied and
      were not interested in additional injections: 5 with malar fluid, 3 with lumpy
      irregularity, and 3 with color change. CONCLUSIONS: Complex 3-dimensional
      contours and thin skin over bone render periorbital filling difficult. However,
      with individualized planning and with care taken to create smooth, feathered
      contours, it is possible to achieve acceptable improvement. We found that most
      patients considered themselves improved cosmetically, despite occasional side
      effects including contour irregularity or lumps, bruising, color change, and
      fluid accumulation. Patients with very thin skin, preexisting color problems, or
      preexisting eyelid fluid may not be good candidates for periorbital filling with
      hyaluronic acid gel. The effect of the filler is temporary, of course, and we
      counsel patients to anticipate maintenance injections at 6- to 12-month
      intervals.

PMID- 16985416
TI  - Deep-fill hyaluronic acid for the temporary treatment of the naso-jugal groove: a
      report of 303 consecutive treatments.
AB  - PURPOSE: To report a 2-year experience of treating the naso-jugal groove with
      injectable hyaluronic acid gel, using a deep-fill method. METHODS: This was a
      consecutive, retrospective, nonrandomized case series of patients presenting with
      concerns involving dark circles, lower eyelid hollows, or other contour
      irregularities that make up the naso-jugal groove. One author performed all
      treatments, consisting of transcutaneous injection of hyaluronic acid gel filler,
      to address the naso-jugal groove. The filler was placed deep on the anterior lip
      of the orbital rim and molded to the desired shape. RESULTS: Between December
      2003 and December 2005, 164 patients (34 male and 130 female) received hyaluronic
      acid gel filler in the face. Ninety-eight patients were treated just once and 66
      had multiple treatment sessions. The mean dose of filler per session was 1.53 +/-
      0.8 ml, with 0.84 +/- 0.38 ml divided between the two lower eyelids. The most
      common complication was localized swelling, followed by bruising, asymmetry,
      cellulitis (2 cases), and migraine (1 case). There were no cases of visual loss.
      CONCLUSIONS: Hyaluronic acid gel fillers have had an enormous impact on the
      practice of cosmetic surgery, and this series demonstrates the usefulness of
      these fillers for treatment of the lower eyelid and midface. The authors
      recommend the deep-fill method described as a reliable means of addressing the
      hollow created by the naso-jugal groove.

PMID- 16985417
TI  - Treatment of trichiasis and distichiasis by eyelash trephination.
AB  - PURPOSE: To describe the methods and results of a new technique of eyelash
      trephination for treatment of trichiasis and distichiasis. METHODS: The medical
      records of all patients who underwent eyelash trephination by the authors to
      treat trichiasis or distichiasis were reviewed. Gender, diagnosis, number of
      eyelids treated, follow-up time, and surgical outcome were recorded. The
      technique involves boring of the affected lash follicle with a microtrephine,
      followed by removal of the follicle. RESULTS: The procedure was performed on 41
      eyelids of 26 patients (15 females and 11 males). Patients were followed for 6 to
      51 months after surgery. No recurrence was observed in 16 patients (62%) during
      this period. There were no adverse effects of the therapy. CONCLUSIONS: Eyelash
      trephination is a safe, quick, and effective method of treatment for trichiasis
      and distichiasis.

PMID- 16985418
TI  - A permanent and reversible procedure to block tear drainage for the treatment of
      dry eye.
AB  - PURPOSE: To describe a technique of canalicular ligation and report observations
      on 59 consecutive surgeries. METHODS: Retrospective, non-comparative case series
      of canalicular ligation by 3 surgeons over a 7-year period. RESULTS: Fifty-nine
      eyelids of 29 patients (2 men and 27 women) underwent canalicular ligation for
      the treatment of severe dry eyes. Patient age ranged from 34 to 90 years. Average
      length of follow-up was 20 months. There were no complications. Ninety-one
      percent of patients noted an improvement in their symptoms. Two patients
      developed symptomatic epiphora more than 1 year postoperatively and both
      underwent successful reversal. CONCLUSIONS: Canalicular ligation is an effective
      technique for punctal occlusion in patients with severe dry eyes. It combines
      surgical ease with excellent cosmetic outcomes.

PMID- 16985419
TI  - En bloc excision in malignant tumors of the lacrimal drainage apparatus.
AB  - PURPOSE: To describe the surgical technique and results of en bloc excision in a
      series of patients with extensive malignant tumors of the lacrimal drainage
      apparatus (LDA). METHODS: This was a noncomparative, retrospective chart review
      of the clinical and pathologic findings of 11 patients presenting with a
      malignant tumor affecting the LDA who underwent en bloc excision of the lacrimal
      system. RESULTS: Of the 11 patients, 7 were male. The mean age at presentation
      was 58 years (range, 39 to 81 years), and all cases were unilateral.
      Histopathology revealed 4 squamous cell carcinomas, 3 transitional cell
      carcinomas, 2 mucoepidermoid carcinomas, and 2 melanomas. Epiphora and a mass
      were the most common presentations. An external lesion could be identified in 4
      cases. Irrigation of the lacrimal system revealed nasolacrimal duct obstruction
      in 2 cases and common canaliculus obstruction in another 2 patients. The entire
      LDA and surrounding bony tissues were excised through a lateral rhinotomy
      approach. Adjuvant radiotherapy was given in 4 cases. Nine patients remain alive
      and well after a mean follow-up of 2 years (range, 6 months to 7 years). Three
      cases showed distant disease and 2 patients died of metastatic melanoma
      involvement. CONCLUSIONS: The use of en bloc excision as a radical treatment to
      remove the complete LDA and surrounding bony structures affords good local tumor
      control and may provide the best opportunity for enhanced patient survival.

PMID- 16985420
TI  - Preliminary study of positron emission tomography in the detection and management
      of orbital malignancy.
AB  - PURPOSE: To determine the clinical efficacy of positron emission tomography (PET)
      in the treatment of patients with orbital malignancy. METHODS: Prospective,
      consecutive case series to assess the ability of PET to (1) identify lesions
      previously demonstrated on CT or MRI; (2) characterize the metabolic activity of
      these lesions; and (3) determine the presence of metabolically active metastases
      elsewhere in the body. RESULTS: Eighteen patients with suspected orbital
      malignancies, ages 32 to 78 years, underwent PET in addition to CT and/or MRI.
      Sixteen of 18 also underwent orbital biopsy. Histopathologic diagnosis included
      lymphoma (55%), carcinoma (22%), melanoma (11%), sarcoma (5.5%), and lymphoid
      hyperplasia (5.5%). All orbital lesions were seen on conventional imaging.
      Overall, 61% of orbital lesions were demonstrated on PET, including 55% of tumors
      that were lymphoproliferative and 100% (n = 5) of other malignancies. PET was
      useful in ruling out tumor recurrence after exenteration in 2 patients.
      CONCLUSIONS: In this small clinical series, PET proved effective in demonstrating
      nonlymphoproliferative orbital malignancy. This series is too small to study any
      correlation between histopathologic aggressiveness and PET findings in orbital
      lymphoma.

PMID- 16985421
TI  - Surgical management of locally advanced adenoid cystic carcinoma of the lacrimal
      gland.
AB  - PURPOSE: To review our experience with multidisciplinary surgical management of
      locally advanced adenoid cystic carcinoma of the lacrimal gland. METHODS: We
      present a case series of 7 patients with lacrimal gland adenoid cystic carcinoma
      treated at our institution between June 2001 and October 2003. Clinical records,
      histologic sections, and radiographic images were reviewed. RESULTS: The study
      included 3 men and 4 women (mean age at diagnosis, 44 years). All 7 patients
      underwent an orbital exenteration with bone removal. Five patients had an
      orbitectomy through a craniotomy approach and 2 patients had an exenteration
      through a fronto-orbito-zygomatic approach, all with removal of the bone of the
      superior and lateral wall. Six patients underwent reconstruction of the socket
      through the use of a vascularized flap. The surgical approach involved a
      neurosurgeon, an oculoplastic or head and neck surgeon, and a plastic surgeon.
      Six patients received postoperative radiation therapy. One patient with a
      recurrent tumor had already received radiation therapy, which precluded
      additional radiation therapy after surgical resection. The radiation field
      included the orbit and the skull base because all patients had evidence of
      perineural invasion. As of this writing, there have been no local recurrences.
      Five patients had development of distant metastases and died of disease, at
      follow-up times from 12 to 32 months after surgery. Two patients are alive
      without evidence of disease, both at 24 months' follow-up. CONCLUSIONS:
      Orbitectomy with bone removal may be indicated for achieving local and regional
      control in advanced cases of adenoid cystic carcinoma of the lacrimal gland. This
      surgery does not decrease the risk of distant metastasis. The cases in our series
      highlight the locally invasive and metastatic behavior of this cancer.

PMID- 16985422
TI  - Standardized terminology for aesthetic ophthalmic plastic surgery.
AB  - PURPOSE: To determine whether existing Systemized Nomenclature of Medicine
      (SNOMED) terminology adequately describes aesthetic concepts commonly encountered
      in the oculoplastic and facial plastic surgery setting. METHODS: This was a
      noncomparative case series. A panel of three oculoplastic surgeons compiled a
      list of unique concepts describing specialized aesthetic terminology commonly
      encountered in the oculoplastic and facial plastic surgery setting, with a
      specific focus on anatomic structures and descriptive findings. A standard
      electronic browser was used to manually search for the existence of equivalent
      matching concepts in SNOMED. A quality of match score from 1 to 3 was used with
      values of (1) no match, (2) partial match, and (3) equivalent match. RESULTS: An
      assessment of the existing aesthetic terminology revealed that a majority of
      concepts were not represented. Of 62 total concepts, 68% had no match, 13% had a
      partial match, and 19% had a complete match. CONCLUSIONS: SNOMED coverage of
      aesthetic terminology was less than in previous studies examining content
      representation for other medical topics. Such findings underscore a need for
      further development and refinement of aesthetic content.

PMID- 16985423
TI  - Plasma leptin levels in patients with floppy eyelid syndrome.
AB  - PURPOSE: To determine the range of plasma leptin levels in patients with floppy
      eyelid syndrome (FES). METHODS: This was a retrospective, noninterventional case
      series of 11 patients with FES. Charts were reviewed for patient age, sex, plasma
      leptin level, body mass index (BMI), presence or absence of obstructive sleep
      apnea (OSA) and diabetes mellitus, and any treatments for OSA. RESULTS: Charts of
      11 patients were reviewed (10 male, 1 female). Plasma leptin levels were elevated
      in 7 of 11 patients (64%). Mean plasma leptin concentration was 49.5 ng/ml in
      male patients (range, 5 to 120 ng/ml) compared with a normal range of 1 to 35
      ng/ml. Plasma leptin level in the female patient was 180 ng/ml (normal range, 4
      to 72 ng/ml). Five patients had a known diagnosis of OSA. Four of these patients
      received continuous positive airway pressure during leptin level measurement.
      Plasma leptin levels averaged 110.0 ng/ml in the continuous positive airway
      pressure group. Average BMI was 37.4 kg/m (range, 24.9 to 57.1 kg/m). All
      patients with elevated leptin levels had a high BMI. CONCLUSIONS: Patients with
      FES demonstrate elevated plasma leptin levels, which correlate with BMI.
      Hyperleptinemia may play a role in the pathogenesis of FES.

PMID- 16985424
TI  - Mesenchymal chondrosarcoma of the orbit.
AB  - PURPOSE: To describe a patient with mesenchymal chondrosarcoma of the orbit,
      review clinical and imaging findings, and refine the differential diagnosis from
      other tumors of the orbit. METHODS: Interventional case report and literature
      review. RESULTS: A 21-year-old woman with a 6-month history of progressive
      proptosis presented with left-sided visual loss of recent onset. CT revealed a
      clearly outlined heterogeneous mass with calcified foci, whereas MRI showed an
      isointense signal to gray matter on T1- and T2-weighted images. The patient was
      diagnosed with mesenchymal chondrosarcoma of the orbit only after orbitotomy and
      subsequent histopathologic study. After surgery, she received adjuvant therapy
      with irradiation of the orbit. CONCLUSIONS: Mesenchymal chondrosarcoma is a rare
      malignant tumor of the orbit capable of mimicking several other lesions. Early
      diagnosis requires a high level of suspicion, particularly with regard to
      internally calcified lesions. The treatment of choice is complete surgical
      resection, or, when the tumor is not resectable or residual mass is present after
      surgery, chemotherapy and radiotherapy. Prognosis for patients with orbital
      mesenchymal chondrosarcoma is tentative at best, in part because of the rarity of
      the lesion.

PMID- 16985425
TI  - Fibrous dysplasia of the orbital region: current clinical perspectives in
      ophthalmology and cranio-maxillofacial surgery.
AB  - PURPOSE: To describe the multidisciplinary diagnosis and treatment of patients
      with orbital fibrous dysplasia, a slowly progressive disease that may lead to
      asymmetry, disfigurement, and functional ocular problems. METHODS: Ten patients
      with orbital fibrous dysplasia underwent bifrontal craniotomy through a coronal
      flap, with the removal of the supraorbital arch and dysplastic process involving
      the anterior and middle base of the skull. Four patients underwent superior
      orbital fissure and optic nerve canal decompression. Reconstruction was performed
      by using an autologous bone graft for both the adults and children, in whom a rib
      graft was preferred. The mean follow-up was 53.2 +/- 18.3 months (range, 14 to 94
      months). The patients' preoperative status and postoperative status were
      compared. RESULTS: The immediate and long-term morphologic and aesthetic results
      were good in all cases. All of the patients complained of some degree of diplopia
      during the immediate postoperative period, but the problem spontaneously resolved
      within 1 to 6 months in all but one case. No postoperative reduction in visual
      function was observed in the patients who underwent optic nerve decompression.
      The only reported complication was the irregular reabsorption of regrafted
      dysplastic bone in one patient. CONCLUSIONS: A multidisciplinary approach to
      orbital fibrous dysplasia is fundamental for treatment planning and execution.

PMID- 16985426
TI  - Retrobulbar hemorrhage nine days after cosmetic blepharoplasty resulting in
      permanent visual loss.
AB  - A healthy 45-year-old man had a retrobulbar hemorrhage 9 days after cosmetic
      upper eyelid blepharoplasty that resulted in permanent visual loss. After
      performing a left lateral canthotomy and cantholysis, intraocular pressure
      returned to normal and vision improved from no light perception to 20/40;
      however, the patient did have permanent visual field loss. To our knowledge, this
      is the longest period of time after blepharoplasty that a retrobulbar hemorrhage
      occurred. Ophthalmologists should have a heightened level of suspicion 1 to 2
      weeks after surgery.

PMID- 16985427
TI  - Cavernous sinus/orbital apex syndrome associated with indwelling orbital catheter
      use.
AB  - A 46-year-old man with a history of right orbital fractures and blindness
      underwent simultaneous fracture repair and enucleation with orbital implantation.
      During surgery, an orbital catheter was placed for administering local anesthesia
      to control postoperative pain. After administration of local anesthesia through
      the catheter on postoperative day 1, the patient had development of a complete
      ptosis, total ophthalmoplegia, mydriasis, vision loss from 20/20 to NLP, and
      hypesthesia of the V1 and V2 trigeminal nerve distribution. Intraocular pressures
      and dilated funduscopic examination were normal. There was no evidence of central
      nervous system effects or respiratory depression. After 4 hours of observation,
      the vision, sensation, motility, ptosis, and pupil response all returned to
      normal. Although rare, contralateral cavernous sinus/orbital apex syndrome may
      occur with indwelling orbital catheter administration of local anesthetic in an
      orbit with fractures.

PMID- 16985428
TI  - Resection of anterior orbital meningoencephalocele in a newborn infant.
AB  - An 11-day-old infant was referred for a large, fleshy swelling at the right
      medial canthus, which was noticed at birth. CT of the skull showed protrusion of
      brain tissue within the mass, from which a diagnosis of meningoencephalocele was
      made. The mass was subsequently resected by a team of physicians represented by
      ophthalmology, otolaryngology, and neurosurgery. Follow-up showed good cosmetic
      and functional results. Meningoencephaloceles usually need prompt attention to
      ensure a good visual and cosmetic result. Imaging before surgery and pathologic
      analysis are both necessary steps to successful management. Prognosis is
      excellent unless associated with other comorbid conditions such as Dandy-Walker
      syndrome, holoprosencephaly, or agenesis of the corpus callosum.

PMID- 16985429
TI  - Juvenile dermatomyositis presenting with periorbital edema.
AB  - Juvenile dermatomyositis is a rare disease that affects the skin and muscles. It
      often presents with a classic heliotrope eyelid rash. We present a case of
      juvenile dermatomyositis presenting with significant bilateral periorbital edema,
      with its complete resolution after systemic antiinflammatory therapy.

PMID- 16985430
TI  - CyberKnife radiosurgery and rituximab in the successful management of sclerosing
      idiopathic orbital inflammatory disease.
AB  - A 26-year-old man presented with symptoms suggesting idiopathic orbital
      inflammatory disease. After a poor initial response to oral steroids, an orbital
      biopsy confirmed the diagnosis. A paucicellular lymphocytic infiltrate with areas
      of fibrosis was seen to replace normal tissue. With the development of exposure
      keratopathy and diplopia associated with eyelid retraction, lagophthalmos, and
      decreased motility, increasing doses of steroids and intralesional steroid
      injections were instituted without effect. On the basis of successful treatment
      of malignant lymphocytic lesions, he was treated with CyberKnife radiosurgery and
      rituximab. This resulted in symptom resolution with improved eyelid closure and
      motility. Eighteen months after treatment, he is essentially symptom-free, with
      almost complete radiographic regression of his disease process.

PMID- 16985431
TI  - Thyroid eye disease presenting after cosmetic botulinum toxin injections.
AB  - A 53-year-old woman with left periorbital swelling 4 days after botulinum toxin
      injection in the lateral canthal area presented after noticing left eye
      prominence. Physical examination demonstrated proptosis and eyelid retraction.
      Computed tomography of the orbits confirmed extraocular muscle enlargement
      consistent with thyroid eye disease. In this case, the patient had development of
      proptosis after receiving botulinum toxin injections. Although the proptosis may
      represent progression of the patients' thyroid eye disease, it is worthwhile to
      consider incitation by botulinum toxin as a possible cause given its widespread
      use.

PMID- 16985432
TI  - Orbital cysts lined with both stratified squamous and columnar epithelia: a late
      complication of silicone implants.
AB  - Two patients presented with orbital cysts 5 and 7 years after orbital blowout
      fracture repair with silicone plate implants. The orbital cysts caused
      significant exophthalmos and restriction in ocular motility. Surgical excision
      revealed thick-walled cysts that were displacing the globe and encapsulating the
      silicone implant. On histopathologic examination, the cysts were lined with both
      stratified squamous and ciliated columnar (respiratory) epithelia. We propose
      that squamous and respiratory epithelial cells may have been deposited during
      surgery from the conjunctival and sinus epithelia, respectively. This case series
      illustrates that although an uncommon complication, epithelium-lined inclusion
      cysts may develop several years after orbital fracture repair with a silicone
      implant. A transconjunctival surgical approach is a possible risk factor.

PMID- 16985433
TI  - Lymphoplasmacytic lymphoma isolated to an extraocular muscle.
AB  - A 44-year-old woman presented with a 1-month history of right-sided tearing,
      redness, and chronic headache. Clinical examination was notable for 4-mm
      proptosis and decreased visual acuity OD. Orbital CT demonstrated isolated
      enlargement of the right lateral rectus. Surgical biopsy was undertaken after an
      unsuccessful trial of oral steroids. Histopathology and immunophenotyping
      demonstrated a lymphoplasmacytic lymphoma. External beam radiation induced
      regression of the lymphoma with decreased proptosis and improved visual acuity.

PMID- 16985434
TI  - Large, rapidly growing pilomatrixoma of the upper eyelid.
AB  - A 41-year-old woman presented with a rapidly growing mass on her upper left
      eyelid that had first appeared 3 months earlier. The mass was dark red in color,
      alternating with whitish pseudocyst formations, and measured 3 cm long with a 1
      cm base presenting. The rapid growth had caused a mechanical ptosis and bleeding
      as the result of erosion of the skin covering the tumor. The initial clinical
      diagnosis suggested a malignant lesion or vascular tumor; excisional biopsy was
      performed. The eyelid crease was approached for incision and resection as for a
      blepharoplasty. Pathologic examination yielded a diagnosis of giant
      pilomatrixoma. Pilomatrixomas are rare in adults and rarely attain such a large
      size. After 1 year of follow-up, no recurrence of the tumor has been observed.

PMID- 16985435
TI  - Re: "clinical features and treatment of graves ophthalmopathy in pediatric
      patients".

PMID- 16985437
TI  - Re: "effect of exophthalmometer design on its accuracy".

PMID- 16985438
TI  - Re: "the tetracaine provocation test (TPT) for inducing early involutional
      entropion".

PMID- 16985439
TI  - Surgical outcome of posterior decompression for cervical spondylosis with
      unilateral upper extremity amyotrophy.
AB  - STUDY DESIGN: Case studies of patients with cervical spondylosis with unilateral
      upper extremity amyotrophy. OBJECTIVE: To clarify the surgical outcome of
      posterior decompression for this amyotrophy. SUMMARY OF BACKGROUND DATA: Cervical
      spondylosis sometimes causes a characteristic severe muscular atrophy without
      sensory disturbance or lower-extremity dysfunction, which is the so-called
      "cervical spondylotic amyotrophy." However, response to treatment, especially to
      posterior decompression, has not been well understood. METHOD: This study
      included 32 patients. All underwent posterior cervical laminoplasty, and 22
      patients had an additional foraminotomy. Preoperative and postoperative muscle
      power and results of imaging and electrophysiologic studies were evaluated. The
      follow-up period averaged 78 months. Whether impingement was against the ventral
      nerve root (VNR) or anterior horn (AH) in the spinal cord was assessed according
      to these findings. These cases were divided into proximal type and distal type
      according to the most severely atrophic muscle and compared statistically.
      RESULTS: Severe preoperative muscle atrophy was observed in the deltoid and
      biceps muscles of 24 patients (proximal type) and in the forearm and hand muscles
      of 8 patients (distal type). Impingements against the VNR and AH were observed in
      21 and 28 cases, respectively, and 17 cases had impingement of both the VNR and
      AH. Improvements in muscle atrophy after surgery were observed in 25 cases. In
      proximal-type patients, muscle power improved in 92% of cases but was improved in
      only 38% of the distal-type cases. CONCLUSIONS: Laminoplasty and foraminotomy
      were effective in the treatment of most patients with this syndrome, although the
      outcome in the distal type was inferior to that in the proximal type.

PMID- 16985440
TI  - Stabilizing effect of precontracted neck musculature in whiplash.
AB  - STUDY DESIGN: This study investigated the effect of neck muscle precontraction in
      aware occupants in whiplash. Head angulation relative to T1 and facet joint
      capsular ligament distractions were compared between aware and unaware occupants.
      OBJECTIVE: To quantify changes in facet joint capsular ligament distractions
      between aware occupants with precontracted neck muscles and unaware occupants
      with reflex muscle contraction. SUMMARY OF BACKGROUND DATA: Clinical studies have
      reported that patients aware of the impending impact had decreased symptom
      intensity and faster recovery after whiplash. To date, no study has investigated
      the effects of precontracted neck musculature on localized spinal soft tissue
      distortions in whiplash. METHODS: Aware occupants with precontracted neck muscles
      and unaware occupants with reflex muscle contraction in whiplash were simulated
      using a validated computational model. Muscle contraction attained maximum levels
      before impact in the aware occupant and implemented reflex delay,
      electromechanical delay, and finite muscle rise time in the unaware occupant.
      RESULTS: Precontraction of neck muscles in aware occupants resulted in 63%
      decreased maximum head angles, elimination of cervical S-curvature, and up to 75%
      decrease in maximum facet joint capsular ligament distractions. CONCLUSIONS:
      Occupants aware of an impending whiplash impact with precontracted neck muscles
      can markedly reduce overall head-neck and spinal motions. It is our theory that
      this would reduce whiplash injury likelihood.

PMID- 16985441
TI  - Ultrasound-guided spinal fracture repositioning, ligamentotaxis, and remodeling
      after thoracolumbar burst fractures.
AB  - STUDY DESIGN: Computed tomography aided evaluation of spinal decompression by
      ultrasound-guided spinal fracture repositioning, ligamentotaxis, and remodeling
      after thoracolumbar burst fractures. OBJECTIVES: To determine the necessity of
      spinal canal widening by ultrasound-guided fracture repositioning for fractures
      with and without neurologic deficit. SUMMARY OF BACKGROUND DATA: Ultrasound
      guided spinal fracture repositioning is an alternative new approach. Reports have
      varied concerning ligamentotaxis and remodeling. METHODS: Computed tomography
      aided planimetry of the spinal canal (64 consecutive burst fractures) and
      neurologic evaluation by Frankel grades. RESULTS: Ultrasound-guided spinal
      fracture repositioning (n = 37) reduced the stenosis of the spinal canal area
      from 45% before surgery to 20% after surgery of the estimated original area.
      Fifteen patients had a primary neurologic deficit, which improved markedly in 11
      cases after treatment. Patients with neurologic symptoms had a greater
      preoperative spinal stenosis than those without. No correlation was seen between
      the degree of pretreatment spinal stenosis, fracture type, and severity of the
      neurologic deficit. Ligamentotaxis (n = 27) reduced the stenosis from 30% before
      surgery to 18% after surgery and remodeling (n = 11) from 25% after surgery to
      13% after metal removal. CONCLUSION: Ultrasound-guided fracture repositioning is
      an efficient method for spinal canal decompression of burst fractures with
      neurologic symptoms. The marked degree of widening of the spinal canal due to the
      effects of ligamentotaxis and remodeling may render the reposition of retropulsed
      fragments unnecessary in cases of fractures without a neurologic deficit.

PMID- 16985443
TI  - Cantilever TLIF with structural allograft and RhBMP2 for correction and
      maintenance of segmental sagittal lordosis: long-term clinical, radiographic, and
      functional outcome.
AB  - STUDY DESIGN/SETTING: Prospective cohort study in a tertiary care spine center.
      OBJECTIVE: The effectiveness of the cantilever transforaminal lumbar interbody
      fusion (C-TLIF) technique in creating and maintaining lordosis, avoiding nerve
      problems, and obtaining fusion was studied. SUMMARY OF BACKGROUND DATA: C-TLIF is
      a microscope-assisted transforaminal lumbar interbody fusion technique,
      emphasizing no dural retraction with placement of structural allograft and RhBMP2
      anteriorly under the cortical apophyseal ring, followed by middle column
      cancellous autograft placed under compression with posterior pedicle spinal
      instrumentation. METHODS: A total of 100 consecutive patients studied with an
      average of 30 months of follow-up. A total of 48 had prior surgery at the index
      level; 16 had the procedure done at an adjacent level to a previous fusion; 32 at
      L5-S1 with 42 at L4-L5 and 26 at L3-L4. There were 76 single-level and 24 two
      level fusions. One patient was a smoker with one other patient a compensation
      case. Outcome was prospectively documented with self-administered Visual Analog
      Pain Scale, Oswestry Disability Questionnaire, Treatment Intensity Questionnaire,
      and SF-36 Health Survey. Patients rated the surgery as excellent, good, fair, or
      poor and whether they would recommend the surgery. Student t test was used for
      statistical analysis with significance set at P = 0.05. RESULTS: Blood loss and
      hospital stay averaged 300 mL and 2.2 days, respectively. There was significant
      reduction (P < 0.05) in pain scores from 9 to 3, Oswestry Disability Index scores
      from 35 to 12, and Treatment Intensity Score from 21/25 to 2/25 at final follow
      up. The SF-36 PCS and MCS scores showed an increasing trend to improvement. A
      total of 69 rated the surgery as excellent, 23 good, 7 fair, and 1 poor. A total
      of 97% were satisfied and would recommend the surgery. All had improvement in
      radicular pain with no dural tears, neural injury, or neuropathic pain. There was
      significant improvement (P < 0.05) in segmental sagittal lordosis from 2 degrees
      to 9 degrees, anterior disc height from 6 to 14 mm, and posterior disc height
      from 4 to 8 mm. There was no subsidence, misplaced screws, or instrumentation
      failure. Solid fusion was obtained in 99 of 100 patients. CONCLUSIONS: The C-TLIF
      allows for creation and maintenance of sagittal lordosis while avoiding
      subsidence and neurologic problems with a 99% fusion rate and 97% patient
      satisfaction.

PMID- 16985444
TI  - Analysis of preexistent vertebral rotation in the normal quadruped spine.
AB  - STUDY DESIGN: In this CT study, vertebral rotation was analyzed in the transverse
      plane of the normal, nonscoliotic canine spine with a computer-based measurement
      method. OBJECTIVES: To determine if a rotational pattern exists in the normal,
      nonscoliotic quadruped spine, similar to what is seen in humans. SUMMARY OF
      BACKGROUND DATA: Idiopathic scoliosis does not occur in quadrupeds. In humans,
      the normal, nonscoliotic spine shows a preexistent pattern of vertebral rotation,
      which corresponds to the most prevalent curve types of idiopathic scoliosis.
      Since this rotational tendency has only been demonstrated in humans, it is not
      clear if it can be considered as a part of the pathogenesis of idiopathic
      scoliosis or as a normal anatomic feature. METHODS: CT scans of the thorax of 42
      dogs without clinical or radiologic evidence of scoliosis were used to measure
      axial vertebral rotation from T1-T13 with a previously developed computer-based
      CT measurement method. RESULTS: The results of this study demonstrated a
      predominant rotation to the right of the upper, mid, and lower thoracic vertebrae
      of the normal canine spine. The mean vertebral rotation angles differed
      significantly from zero degrees rotation at level T1, from level T4-T7, and from
      T11-T13. CONCLUSIONS: The normal spine of quadrupeds shows rotation of the
      thoracic vertebrae with a preferred direction to the right, similar to what is
      seen in humans. Since idiopathic scoliosis does not exist in quadrupeds, this
      preexistent rotation seems to be a physiologic process in normal spinal
      development, independent of the pathogenesis of scoliosis.

PMID- 16985445
TI  - Prognostic factors associated with minimal improvement following acute whiplash
      associated disorders.
AB  - STUDY DESIGN: Retrospective clinical cohort study. OBJECTIVE: To identify the
      prognostic factors associated with a poor response to treatment in the early
      stages of a whiplash-associated disorder (WAD). SUMMARY OF BACKGROUND DATA:
      Several demographic and clinical factors related to recovery following acute WADs
      have been identified. However, few longitudinal studies have investigated a
      multivariable model of recovery that includes socio-demographic, treatment,
      clinical, and nonclinical factors. METHODS: A study cohort of 2,185 patients with
      acute or subacute WADs presenting to 48 rehabilitation clinics in 6 Canadian
      provinces were investigated for factors associated with failure to demonstrate a
      minimally important clinical change (10%) in the Canadian Back Institute
      Questionnaire (CBIQ) score between the initial and discharge rehabilitation
      visits. RESULTS: Multivariable analysis revealed eight prognostic factors
      associated with a negative outcome: 1) older age, 2) female gender, 3) increasing
      lag time between injury date and presentation for treatment, 4) initial pain
      location, 5) province of injury, 6) higher initial pain intensity, 7) lawyer
      involvement, and 8) at work at entry to the clinic. The effect of lawyer
      involvement was stronger for patients with less intense pain on initial visit
      (odds ratio = 2.97; 95% confidence interval, 1.77-4.99). Similarly, the effect of
      work status was stronger for patients with less intense pain on initial visit
      (odds ratio = 2.02; 95% confidence interval, 1.18-3.46). CONCLUSIONS: Researchers
      and clinicians should be aware of the potential for non-injury-related factors to
      delay recovery, and be aware of the interaction between the initial intensity of
      a patient's pain and other covariates when confirming these results.

PMID- 16985447
TI  - Posterior correction and fusion for severe cervical kyphosis in a patient with
      myotonic dystrophy: a case report.
AB  - STUDY DESIGN: A case report. OBJECTIVE: To report the first myotonic dystrophy
      case in which cervical kyphosis had been surgically corrected. SUMMARY OF
      BACKGROUND DATA: Myotonic dystrophy is an autosomal dominant disease that shows
      myotonia, progressive muscle atrophy, and other various symptoms. Instability of
      the neck is expected to cause disorders of the cervical spine; however, there are
      no detailed reports on deformity of cervical spine associated with this disease.
      METHODS: A 43-year-old man with cervical kyphosis due to myotonic dystrophy had
      undergone an occiput-T2 fusion with autogenous iliac bone using spinal
      instrumentation. RESULTS: The activity of daily life of the patient had improved
      markedly, and the good results continued to be preserved for 5 years. There were
      not any major perioperative complications. CONCLUSIONS: Surgical correction of
      cervical spine is not necessarily a contraindication for myotonic dystrophy.

PMID- 16985448
TI  - Infected vertebroplasty due to uncommon bacteria solved surgically: a rare and
      threatening life complication of a common procedure: report of a case and a
      review of the literature.
AB  - STUDY DESIGN: Case report. OBJECTIVE: The aim of this work is to describe a case
      of infected vertebroplasty due to uncommon bacteria solved surgically with 2
      years of follow-up and to discuss 6 other cases found in literature. SUMMARY OF
      BACKGROUND DATA: Vertebroplasty is a well-known and useful technique for the
      treatment of painful osteoporotic vertebral fractures. Complications, such as
      cord or root compression or pulmonary embolisms, are infrequent and are mainly
      related with the frequent escape of cement throughout the vertebral veins.
      Infection is even more rare, but when it occurs is difficult to manage and can be
      a life-threatening complication. METHODS: A 63-year-old-man had a spondylitis of
      L2 after vertebroplasty. The patient was initially managed with antibiotics
      without clinical improvement. Surgical treatment by anterior debridement and
      anterior and posterior stabilization was done. The bacteria isolated from the
      intraoperative cultures were Serratia marcescens, Stenotrophomonas maltophilia,
      and Burkholderia cepacia. After surgery, the patient was treated with antibiotics
      for 3 month. RESULTS: After 2 years of follow-up, the patient was free of pain,
      without signs of infection, and a correct fusion was achieved. CONCLUSION: When
      facing an infected vertebroplasty, initial conservative treatment with needle
      biopsy culture and antibiotic administration are a rational option to start. If
      this treatment fails, surgical debridement is then indicated in order to remove
      the infected tissue and the acrylic cement and to stabilize the spine. Although
      this can be an effective treatment, it could be a difficult and hazardous
      surgical procedure.

PMID- 16985450
TI  - American Board of Orthopedic Surgery (ABOS) Part II oral examination.

PMID- 16985452
TI  - Education: a responsibility, a challenge, and a source of satisfaction.

PMID- 16985453
TI  - Spinal growth and congenital deformity of the spine.

PMID- 16985454
TI  - 2005 Scoliosis Research Society Asian Traveling Fellowship: report to the
      Education Committee.

PMID- 16985455
TI  - Correlates of the peak height velocity in girls with idiopathic scoliosis.
AB  - STUDY DESIGN: Prospective longitudinal. OBJECTIVE: Determine correlates of the
      peak height velocity (PHV) in girls with idiopathic scoliosis. SUMMARY OF
      BACKGROUND DATA: Only identifiable retrospectively, the PHV is the most useful
      known maturity marker in idiopathic scoliosis. Clinically useful correlates are
      needed to make PHV timing helpful. METHODS: A total of 24 immature girls with
      idiopathic scoliosis were followed with serial heights, sexual staging, skeletal
      ages, spinal radiographs, insulin-like growth factor (IGF)-1, IGF binding protein
      3, dehydroepiandrosterone sulfate, estradiol, bone-specific alkaline phosphatase,
      and osteocalcin levels. These markers were correlated to PHV timing. RESULTS:
      There were 14 girls who had identifiable growth peaks that averaged 10.5 +/- 1.8
      cm/y at age 11.7 +/- 1 years. At the PHV, all girls were Risser 0 with open
      triradiate cartilages. On a skeletal age radiograph, digital uncapped phalangeal
      epiphyses were indicative of pre-PHV and fused epiphyses of post-PHV. Capped but
      unfused epiphyses were indeterminate. Tanner stage 1 for breast strongly
      indicates pre-PHV. Stage 3 for breast and pubic hair occurred at or after the
      PHV, and stage 4 always occurred after PHV. Higher IGF-1 and estradiol levels
      after PHV are potentially discriminatory. CONCLUSIONS: The PHV occurs during
      Risser 0 with open triradiate cartilages. If triradiate cartilages are open, then
      Tanner stages, IGF-1, estradiol levels, and the appearance of the epiphyses on a
      skeletal age radiograph are useful in determining status before or after PHV.

PMID- 16985456
TI  - Mechanical testing of a smart spinal implant locking mechanism based on nickel
      titanium alloy.
AB  - STUDY DESIGN: Development and testing of a new spinal implant-locking mechanism
      based on the special properties of nickel-titanium alloy. OBJECTIVE: To develop a
      new self-tightening locking mechanism to reduce fretting corrosion at implant
      junctions. SUMMARY OF BACKGROUND DATA: All current implant locking involves
      tightening of a nut against the rod and screw head to form a coupling.
      Particulate debris is generated, and the coupling becomes loose because of wear
      between the rod and locking mechanism (fretting). To avoid this fretting, a new
      locking mechanism with an automatic retightening effect based on the superelastic
      and shape-memory properties of nickel-titanium alloy has been developed. METHOD:
      The new coupling made of nickel-titanium alloy will tightly lock the rod when
      temperature increases to 50 degrees C (shape-memory effect). If fretting occurs,
      the coupling will further tighten itself around the rod (superelastic effect).
      This new coupling is mechanically tested against 4 current implant couplings.
      RESULTS: In axial compression, conventional couplings failed between 570 and 740
      N, while the new coupling reached 800 N without loosening. In axial rotation,
      conventional devices failed between 1.8 and 5.3 Nm, while the new coupling
      reached 6.5 Nm without failure. During testing, the retightening effect could be
      seen on the force versus displacement plot. CONCLUSIONS: To our knowledge, the
      self-tightening coupling is a new concept not previously described and is
      attributable to the superior superelastic effect of the new coupling. This
      implant coupling has the potential to be used as a very low profile system and
      also in nonfusion technologies in which demands on the coupling would not higher
      without the protection of spinal fusion.

PMID- 16985457
TI  - Change in lordosis at the occipitocervical junction following posterior
      occipitocervical fusion in skeletally immature children.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: Evaluate the change in
      lordosis at the occipitocervical junction occurring during growth in skeletally
      immature children treated with posterior occipitocervical arthrodesis versus
      patients skeletally mature at arthrodesis. SUMMARY OF BACKGROUND DATA: Posterior
      occipitocervical arthrodesis is often indicated for children who have instability
      of the upper cervical spine develop. Theoretically, in skeletally immature
      children, this approach retards the growth of the posterior spinal elements but
      allows the anterior spinal column to continue to grow with the risk of excessive
      lordosis of the cervical spine developing. METHODS: There were 21 children,
      younger than 11 years (range 1.9-10.9) at surgery and expected to have normal
      spinal growth, followed radiographically for an average of 6.3 years (range 2.0
      12.4). Postoperative lateral neutral radiographs were compared to those at most
      recent follow-up to measure the change in occipitocervical angle. These results
      were then compared to a series of control patients who were skeletally mature at
      surgery. RESULTS: Average overall change in lordosis at the occipitocervical
      junction was -4.6 degrees (range -12.8 degrees to +6.5 degrees). Average
      annualized change was -0.28 degrees per vertebral level per year (range -1.13
      degrees to +0.67 degrees). This annualized change in angle was statistically
      significant compared to the average change of +0.01 degrees (range -0.09 degrees
      to +0.11 degrees) measured in the control series of patients skeletally mature at
      surgery (P = 0.01). CONCLUSIONS: Increasing lordosis occurs at the
      occipitocervical junction following fusion in skeletally immature children. If
      occipitocervical arthrodesis is indicated in a skeletally immature child, fusion
      in excessive extension and overtightening of posterior wires should be avoided.

PMID- 16985458
TI  - Fusionless surgery for scoliosis: 2-17 year radiographic and clinical follow-up.
AB  - STUDY DESIGN: Descriptive case series. OBJECTIVE: To determine whether
      fusionless, multiple vertebral wedge osteotomy can safely obtain correction of
      the deformity with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND
      DATA: To our knowledge, no such attempts to manage the AIS with fusionless,
      vertebral osteotomies have been reported. METHODS: A total of 20 consecutive
      patients were treated since 1987. Deformity correction, complications,
      respiratory function, and patient-oriented outcome were investigated. RESULTS:
      There were 20 patients (17 females and 3 males), including 19 with idiopathic and
      1 with syringomyelia scoliosis, who underwent surgery at an average age of 16.4
      years and were followed for 8.9 years (range 2-17) on average. There were no
      neurologic complications. One superficial wound infection necessitated
      debridement. There were 2 patients converted to posterior instrumentation surgery
      because of deterioration of the deformity. The average Cobb angle of 64.0 degrees
      before surgery was corrected to 48.2 degrees at 8.9 years after surgery. Decline
      of the pulmonary function test after surgery was not statistically significant.
      The patients' responses to questions about function and pain were favorable.
      CONCLUSION: Deformity with AIS was safely corrected with fusionless, multiple
      vertebral wedge osteotomy.

PMID- 16985459
TI  - Comparison of Scheuermann kyphosis correction by posterior-only thoracic pedicle
      screw fixation versus combined anterior/posterior fusion.
AB  - STUDY DESIGN: Retrospective comparison review. OBJECTIVE: Compare posterior-only
      treatment results with segmental thoracic pedicle screw constructs versus
      combined anterior/posterior fusion in patients with Scheuermann kyphosis. SUMMARY
      OF BACKGROUND DATA: Traditionally, operative Scheuermann kyphosis has been
      treated with combined anterior/posterior spinal fusion, with the anterior portion
      being performed via an open thoracotomy or a video-assisted thoracoscopic
      approach. METHODS: There were 18 patients with Scheuermann kyphosis who underwent
      a posterior-only thoracic pedicle screw (P/TPS) fusion and 21 who underwent an
      anterior/posterior fusion who were followed for a 2-year minimum. The 2 groups
      were well matched according to average age (anterior/posterior fusion 18.0
      degrees and P/TPS 17.3 degrees; P = 0.60), maximum preoperative kyphosis
      (anterior/posterior fusion 89.1 degrees and P/TPS 84.4 degrees; P = 0.21),
      flexibility index (anterior/posterior fusion 0.408 degrees and P/TPS 0.407
      degrees; P > 0.99), and posterior fusion levels (anterior/posterior fusion 12.1
      degrees and P/TPS 12.2 degrees; P = 0.95). Of 21 patients with anterior/posterior
      fusions, zero versus 12 of 18 (67%) patients in the P/TPS group underwent apical
      Smith-Petersen osteotomies. Fixation in the anterior/posterior fusion group was
      achieved with hybrid hook/screw constructs. Posterior fixation in the P/TPS group
      was performed using segmental thoracic pedicle screw constructs. Both groups had
      posterior iliac bone autografting. Operating time and blood loss were noted, and
      radiographs were evaluated before surgery, after surgery, and at final follow-up.
      At final follow up, Scoliosis Research Society-30 questionnaire data and
      complications were recorded. RESULTS: At surgery, operating time and blood loss
      were significantly less in the P/TPS group (P = 0.009 and P = 0.05,
      respectively). The mean residual kyphosis of the P/TPS group averaged 38.2
      degrees after surgery and 40.4 degrees at final follow-up versus
      anterior/posterior fusion group (51.9 degrees and 58.0 degrees, P < 0.001 and P =
      0.001, respectively). Even without an anterior release, kyphosis correction in
      the P/TPS group averaged 54.2% after surgery and 51.8% at final follow-up versus
      the anterior/posterior fusion group (41.2% and 38.5%, P = 0.001 and P < 0.001,
      respectively). Scoliosis Research Society-30 outcome scores at final follow-up
      were comparable between the 2 groups (P/TPS = 120 and anterior/posterior fusion =
      128; P = 0.14). The anterior/posterior fusion group had 8/21 (38%) patients with
      complications, including paraplegia in 1, proximal junctional kyphosis in 1,
      proximal hook pullout in 1, and infection in 2. The P/TPS group had no
      complications (P = 0.003). CONCLUSIONS: With less operating time and
      intraoperative blood loss, posterior-only Scheuermann kyphosis treatment with
      thoracic pedicle screws achieved and maintained better correction, and had
      significantly less complications than with circumferential fusion.

PMID- 16985460
TI  - Prospective radiographic and clinical outcomes of dual-rod instrumented anterior
      spinal fusion in adolescent idiopathic scoliosis: comparison with single-rod
      constructs.
AB  - STUDY DESIGN: Anterior single or dual-rod instrumentation may be performed for
      the treatment of main thoracic, thoracolumbar, or lumbar adolescent idiopathic
      scoliosis (AIS) curves. OBJECTIVE: To compare the results of anterior dual-rod
      instrumentation in single-major AIS curves with our previous experience using
      single-rod constructs. SUMMARY OF BACKGROUND DATA: Several reports have described
      the use of anterior single-rod instrumentation for the treatment of AIS curves
      with acceptable correction rates but with pseudarthroses/implant failures of up
      to 31%. METHODS: A total of 60 consecutive patients with AIS (12 males and 48
      females; average age 15.3 years) with major thoracic (n = 18) or
      thoracolumbar/lumbar (n = 42) curves were treated with dual-rod instrumented
      anterior spinal fusion. Follow-up was 2-5 years. Patients were evaluated
      prospectively with Scoliosis Research Society (SRS) questionnaires. RESULTS:
      Major thoracic curves were corrected from a mean of 55 degrees to 27 degrees (51%
      correction), while major thoracolumbar/lumbar curves were corrected from an
      average of 51 degrees to 17 degrees at latest follow-up (67% correction). No
      pseudarthroses were identified. With the use of single-rod constructs, a similar
      amount of coronal correction was obtained for both thoracic (47%) and
      thoracolumbar/lumbar curves (70%). However, the pseudarthrosis rate for single
      rod constructs was 5.5%. The obvious trend toward a lower pseudarthrosis rate in
      dual-rod (0/60) versus single-rod (5/90) constructs was not statistically
      significant (P = 0.07). Follow-up SRS questionnaire data for patients with dual
      rod instrumentation showed 95% satisfaction, and 93% would choose the same
      treatment with similar results in the single-rod instrumentation study, 88%
      patient satisfaction, and 89% choosing the same treatment. Overall SRS scores
      improved after treatment (P < 0.01). SRS domain scores improved at a significant
      level for pain (P = 0.05), self-image (P < 0.01), and function (P = 0.01).
      CONCLUSION: In this largest, to our knowledge, single-center report of dual-rod
      constructs for patients with AIS, a similar amount of radiographic deformity
      correction was obtained when compared to single-rod implants. However, the
      absence of any pseudarthroses in the 60 patients with dual-rod is a distinct
      advantage.

PMID- 16985461
TI  - Pseudarthrosis in long adult spinal deformity instrumentation and fusion to the
      sacrum: prevalence and risk factor analysis of 144 cases.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze the incidence of and
      risk factors for pseudarthrosis in long adult spinal instrumentation and fusion
      to S1. SUMMARY OF BACKGROUND DATA: Few studies on pseudarthrosis in long adult
      spinal instrumentation and fusion to S1 exist. METHODS: A clinical and
      radiographic assessment of 144 adult patients with spinal deformity (average age
      52.0 years; range 21.1-77.6) who underwent long (5-17 vertebrae, average 11.9)
      spinal instrumentation and fusion to the sacrum at a single institution between
      1985 and 2002, with a minimum 2-year follow-up (average 3.9; range 2-14) was
      performed. RESULTS: Of 144 patients, 34 (24%) had pseudarthroses. There were 17
      patients who had pseudarthroses at T10-L2 and 15 at L5-S1. A total of 24 patients
      (71%) presented with multiple levels involved (2-6). Pseudarthrosis was most
      commonly detected within 4 years postoperatively (31 patients; 94%). Factors that
      statistically increased the risk of pseudarthrosis were: thoracolumbar kyphosis
      (T10-L2 > or = 20 degrees vs. < 20 degrees, P < 0.0001); osteoarthritis of the
      hip joint (P = 0.002); thoracoabdominal approach (vs. paramedian approach, P =
      0.009); positive sagittal balance > or = 5 cm at 8 weeks postoperatively (vs. <
      or = 5 cm, P = 0.012); age at surgery older than 55 years (vs. 55 years or
      younger, P = 0.019); and incomplete sacropelvic fixation (vs. complete
      sacropelvic fixation, P = 0.020). Fusion from upper thoracic spine (T2-T5) did
      not statistically increase the pseudarthrosis rate compared to lower thoracic
      spine (T9-T12) (P = 0.20). Patients with pseudarthrosis had significantly lower
      Scoliosis Research Society 24 outcome scores (average score 71/120) than those
      without (average score 90/120; P < 0.0001) at ultimate follow-up. CONCLUSION: The
      overall prevalence of pseudarthrosis following long adult spinal deformity
      instrumentation and fusion to S1 was 24%. Thoracolumbar kyphosis, osteoarthritis
      of the hip joint, thoracoabdominal approach (vs. paramedian approach), positive
      sagittal balance > or = 5 cm at 8 weeks postoperatively, older age at surgery
      (older than 55 years), and incomplete sacropelvic fixation significantly
      increased the risks of pseudarthrosis to an extent that was statistically
      significant. Scoliosis Research Society 24 outcomes scores at ultimate follow-up
      were adversely affected when pseudarthrosis developed.

PMID- 16985462
TI  - Anterior instrumentation for thoracolumbar adolescent idiopathic scoliosis: do
      structural interbody grafts preserve sagittal alignment better than morselized
      rib autografts?
AB  - STUDY DESIGN: This is a retrospective, sequential cohort study of 34 patients
      treated by anterior instrumented fusion with single solid rod, single screw
      constructs with at least 2-year follow-up. Sixteen of the patients received
      structural grafts as interbody spacers in disc levels below T12, while the other
      18 patients received only morselized rib autograft. OBJECTIVE: To determine if
      structural interbody grafts preserve sagittal alignment better than morselized
      rib autograft. SUMMARY OF BACKGROUND DATA: Some studies have shown that
      structural grafts are more effective in preserving sagittal alignment, while
      others have found them to be no more effective than morselized rib graft.
      METHODS: Anterior-posterior radiographs were measured for primary, secondary, and
      fractional Cobb curves, and C7-sacrum plumb lines. Lateral radiographs were
      measured for: T5-HIV (highest instrumented vertebrae), instrumented levels, LIV
      (lowest instrumented vertebrae)-S1, T12-LIV, and T12-S1 angles, C7-sacrum plumb
      lines, and LID-A (lowest instrumented disc-angle). RESULTS: The increase in
      kyphosis from preoperative to follow-up radiographs of the angle between T12-LIV
      was significantly more for the patients with morselized rib graft compared with
      those with structural grafts, 9 degrees and 1 degree, respectively (P < 0.05).
      CONCLUSIONS: The structural grafts placed in disc spaces below T12 were able to
      maintain sagittal alignment over this region, while the spines that received only
      morselized rib graft collapsed into kyphosis.

PMID- 16985463
TI  - An analysis of sagittal spinal alignment following long adult lumbar
      instrumentation and fusion to L5 or S1: can we predict ideal lumbar lordosis?
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To determine factors controlling
      sagittal spinal balance after long adult lumbar instrumentation and fusion from
      the thoracolumbar spine to L5 or S1. SUMMARY OF BACKGROUND DATA: To our
      knowledge, no study on postoperative sagittal balance following long adult spinal
      instrumentation and fusion to L5 or S1 has been published. METHODS: A clinical
      and radiographic assessment of 80 patients with adult lumbar deformity (average
      age 53.4 years) who underwent long (average 7.6 vertebrae, 5-11 vertebrae)
      segmental posterior spinal instrumentation and fusion from the thoracolumbar
      spine to the L5-S1 (average 4.5 years, 2-15.8-year follow-up) was performed. We
      defined the optimal sagittal balance (n = 42) group, the distance from C7 plumb
      to superior posterior endplate of S1 < or = 3.0 cm, and the suboptimal sagittal
      balance (n = 38) group, the distance from C7 plumb to superior posterior endplate
      of S1 > 3.0 cm at ultimate follow-up. RESULTS: The optimal sagittal balance group
      (C7 plumb, average -0.6 +/- 2.5 cm) had the larger average angle differences
      between lumbar lordosis and thoracic kyphosis (P < 0.0001), preoperative smaller
      pelvic incidence (P = 0.007), smaller average thoracolumbar junctional angle (T10
      L2) increase (P < 0.0001), and bigger lumbar lordosis angle increase (P = 0.014)
      at ultimate follow-up. Patients with optimal sagittal balance at ultimate follow
      up had significantly higher total Scoliosis Research Society 24 outcome scores
      than those with suboptimal sagittal balance (P = 0.015). Risk factors that were
      statistically significant for the suboptimal sagittal balance group included
      pelvic incidence compared with lumbar lordosis (> or = 45 degrees) before surgery
      (vs. < 45 degrees, P = 0.009), smaller lumbar lordosis compared with thoracic
      kyphosis (< 20 degrees) at 8 weeks postoperatively (vs. > or = 20 degrees, P =
      0.013), and older than 55 years of age at surgery (vs. 55 years or younger, P =
      0.024). CONCLUSION: A sagittal Cobb angle difference between lumbar lordosis and
      thoracic kyphosis of > 20 degrees (higher lumbar lordosis) is advisable in most
      circumstances to achieve optimal sagittal balance.

PMID- 16985464
TI  - Degenerative lumbar scoliosis: radiographic correlation of lateral rotatory
      olisthesis with neural canal dimensions.
AB  - STUDY DESIGN: A radiographic review of 78 consecutive patients with degenerative
      rotatory lumbar scoliosis. OBJECTIVE: To assess the correlation between rotary
      olisthesis and neural canal dimensions using radiographic indexes and to
      establish a gradation system of lateral rotatory olisthesis. SUMMARY OF
      BACKGROUND DATA: Degenerative scoliosis is a three-dimensional deformity often
      associated with spinal stenosis, although the association is not well defined.
      METHODS: A total of 78 consecutive patients (average age, 69 years) with de novo
      degenerative scoliosis (79% lumbar, 21% thoracolumbar; average curve, 25 degrees)
      were studied with plain radiographs and MRI at presentation. Radiographic
      measurements included lateral translation, anteroposterior olisthesis, Cobb
      angle, and intervertebral rotation (Nash-Moe grade difference). Computerized
      measurements of MRI included dural sac cross-sectional area and anteroposterior
      diameter, minimum subarticular height, and foramen cross-sectional area
      bilaterally (convexity and concavity). Measurements were conducted twice on each
      lumbar level (total, 312) and the average was recorded. RESULTS: Lateral
      translation 5 mm or less (Grade I) was associated with Nash-Moe change 0 (23%) or
      I (77%), lateral translation 6-10 mm (Grade II) was coupled with Nash-Moe change
      0 (20%) or I (80%) and lateral deviation more than 11 mm (Grade III) was
      associated with I (76%) or II (24%) Nash-Moe change. Maximum intervertebral
      rotation tended to be at either L2-L3 (48%) or L3-L4 (39%). Increased lateral
      translation was associated with increased intervertebral rotation (r = 0.37, P <
      0.001). Increased anteroposterior olisthesis was associated with decreased
      anteroposterior diameter (r = -0.18, P < 0.001) and cross-sectional area (r = 
      0.11, P < 0.05) of the dural sac. Larger segmental Cobb angles were associated
      with greater foraminal cross-sectional area in the convexity (r = 0.12, P <
      0.05). In the concavity, there was no significant correlation (P > 0.05) between
      indexes of rotary olisthesis and foraminal area or subarticular height. Cross
      sectional foraminal area and subarticular height were significantly larger in the
      convexity than in the concavity of the scoliotic levels. CONCLUSIONS: In
      degenerative scoliotic curves, lateral translation is associated with rotation.
      Increased rotary olisthesis does not lead to decreased dural sac area.
      Anteroposterior olisthesis is inversely correlated to the dural sac
      anteroposterior diameter and cross-sectional area. With increased segmental Cobb
      angle, foraminal cross-sectional area enlarges in the convexity and does not
      decrease in the concavity. Presence of intervertebral rotation alone does not
      appear to be associated with reduced neural canal dimensions. Ligamentum flavum
      hypertrophy, posterior disc bulging, and bony overgrowth are more likely to
      contribute to stenosis irrespective of scoliosis.

PMID- 16985465
TI  - Sagittal thoracic decompensation following long adult lumbar spinal
      instrumentation and fusion to L5 or S1: causes, prevalence, and risk factor
      analysis.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze the causes, prevalence
      of, and risk factors for sagittal thoracic decompensation in adult lumbar spinal
      instrumentation and fusion (from distal thoracic or upper lumbar spine) to L5 or
      S1. SUMMARY OF BACKGROUND DATA: To our knowledge, no studies on sagittal thoracic
      decompensation following long adult lumbar spinal instrumentation and fusion
      (from distal thoracic or upper lumbar spine) to L5 or S1 have been published.
      METHODS: A clinical and radiographic assessment of 99 patients with adult lumbar
      spinal deformity (average age 56.7 years) who underwent long (> or = 4 vertebrae;
      range 4-10/average 6.7) spinal instrumentation and fusion (from lower thoracic or
      upper lumbar spine to L5 or S1) at a single institution between 1985 and 2003
      with a minimum 2-year follow-up (average 4.5 years) was performed. We defined
      sagittal thoracic decompensation as a progressive kyphotic deformity of the
      thoracic spine without pseudarthrosis after a long lumbar fusion, which
      subsequently resulted in a C7 plumb relative to the posterior aspect of the L5-S1
      disc > or = 8 cm. RESULTS: The prevalence of sagittal thoracic decompensation
      after long adult lumbar spinal instrumentation and fusion (from distal thoracic
      or upper lumbar spine) to L5 or S1 was 23% (23/99 cases). The etiologies were 14
      acute sharp angular kyphoses and 9 long sweeping kyphoses above the instrumented
      fusion. Of the 14 sharp angular kyphoses, 10 occurred from severe disc
      degeneration and 4 were caused by compression fractures at the uppermost
      instrumented vertebra. CONCLUSION: Risk factors for sagittal thoracic
      decompensation developing were sagittal imbalance at 8 weeks postoperatively (>
      or = 5 cm), smaller lumbar lordosis compared with thoracic kyphosis (< 10
      degrees) at 8 weeks postoperatively, preoperative sagittal imbalance (> or = 5
      cm), age at surgery (older than 55 years), and associated comorbidities. Sagittal
      thoracic decompensation adversely affected Scoliosis Research Society 24 outcomes
      scores.

PMID- 16985466
TI  - Parents' and patients' perceptions of postoperative appearance in adolescent
      idiopathic scoliosis.
AB  - STUDY DESIGN: A cross-sectional evaluation of patients after surgery for
      adolescent idiopathic scoliosis (AIS). OBJECTIVES: To determine the agreement
      between patients' and parents' perceptions of the patient's postoperative
      appearance and to compare those perceptions with physical and radiographic
      measures of deformity. SUMMARY OF BACKGROUND DATA: Improving cosmesis is an
      important aim of surgery. Patients' appearances may influence their evaluation of
      its outcome. METHODS: Physical and radiographic data were collected 2 years after
      surgery for 128 patients with AIS. Patients and parents independently rated
      shoulder blades, shoulders, waist, and overall appearance. Additionally, patients
      completed the Quality of Life Profile for Spinal Disorders (QLPSD). Agreement was
      evaluated with the weighted kappa statistic ranging between 0 and 1 where higher
      values indicate better agreement. RESULTS: Fair to moderate agreement was found
      between patient and parent ratings of the patient's shoulder blades (kappa =
      0.39; 95% confidence interval [CI], 0.29-0.48), shoulders (kappa = 0.38; 95% CI,
      0.26-0.50), waist (kappa = 0.45; 95% CI, 0.25-0.55), and overall appearance
      (kappa = 0.22; 95% CI, 0.04-0.40). Patients rated the appearance of their waist
      (P = 0.013) and overall appearance (P = 0.039) significantly worse than their
      parents. Patients' perceptions of their overall appearance had higher
      correlations with the body image subscale score (r = 0.45, P = 0.000) and the
      total quality of life score on the QLPSD (r = 0.37, P = 0.000) than did parents'
      perceptions of those same measures (r = 0.21, P = 0.025; and r = 0.08, P = 0.369,
      respectively). CONCLUSIONS: Radiographic and physical measures of deformity do
      not correlate well with patients' and parents' perceptions of appearance.
      Patients and parents do not strongly agree on the cosmetic outcome of AIS
      surgery. Therefore, given that the adolescents themselves undergo the surgery,
      patients' assessments of their deformity, rather than radiographic measures or
      parents' assessments, should play a major role in the evaluation of surgical
      success.

PMID- 16985467
TI  - Wasting of preoperatively donated autologous blood in the surgical treatment of
      adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Retrospective, case-control. OBJECTIVE: Evaluate the utility of
      preoperative autologous blood donation (PABD) for surgical treatment of
      adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Recent data
      have highlighted overuse of PABD in elective surgery; however, PABD is a major
      blood conservation strategy for AIS surgery. METHODS: Medical records of 123
      patients treated for AIS between June 1995 and November 2004 were reviewed.
      Patients were divided into PABD (n = 104) and nondonors (NPABD; n = 19). RESULTS:
      No differences existed between PABD and NPABD for age, major curve size, or
      operative procedures. Average PABD preoperative hematocrit was lower than NPABD
      (37.8 vs. 40.2; P < 0.005). PABD patients were 9 times more likely to be
      transfused than NPABD, and 3 times more likely to be transfused for each unit
      donated. There was a 25% transfusion risk reduction for each percent preoperative
      hematocrit increase. Minimum one autologous unit was not transfused in 32
      patients (31%). Twenty-nine PABD patients (28%) were transfused for hematocrit
      >30. Fifty-three PABD patients (51%) wasted at least one unit or were transfused
      for hematocrit >30. CONCLUSIONS: The majority of PABD patients (51%) wasted
      minimum one autologous unit or were transfused at a high hematocrit (>30). More
      precise PABD guidelines are needed to limit unnecessary transfusion and wasted
      resources.

PMID- 16985468
TI  - Analysis of patients with nonambulatory neuromuscular scoliosis surgically
      treated to the pelvis with intraoperative halo-femoral traction.
AB  - STUDY DESIGN: Retrospective case-control study. OBJECTIVES: To compare patients
      treated with and without intraoperative halo-femoral traction to assess
      neuromuscular spinal deformity correction as well as the safety of the technique.
      SUMMARY OF BACKGROUND DATA: Optimal sitting balance can be achieved in
      nonambulatory neuromuscular patients with pelvic obliquity by maneuvering a
      Galveston-type rod or inserting screws into the iliac wings; however, this is
      often clinically challenging because of the small, soft bone-stock in the pelvis
      of these patients. METHODS: A total of 40 patients with nonambulatory
      neuromuscular scoliosis were treated surgically with a T2 or T3-sacrum
      instrumented posterior spinal fusion. There were 20 patients (12 who underwent
      posterior spinal fusion-alone and 8 anterior/posterior spinal fusion) who had
      intraoperative halo-femoral traction performed unilaterally on the high side
      iliac wing compared to a control group of 20 patients (15 who underwent posterior
      spinal fusion-alone and 5 anterior/posterior spinal fusion) operatively treated
      without halo-femoral traction. Each group had 14 patients with spastic (cerebral
      palsy) scoliosis, and 6 with flaccid (muscular dystrophy) scoliosis deformities.
      Minimum follow-up for all patients was 2 years (range 3-12). RESULTS:
      Preoperative lumbar scoliosis averaged 87 degrees (range 30 degrees-141 degrees)
      in the halo-femoral traction group and 67 degrees (range 28 degrees-108 degrees)
      in the control group (P = 0.012). Postoperative lumbar Cobb decreased to 35
      degrees (range 15 degrees-60 degrees) in the halo-femoral traction group and 32
      degrees (range 4 degrees-66 degrees) in the control group (P = 0.181).
      Preoperative pelvic obliquity averaged 26 degrees (range 8 degrees-47 degrees) in
      the halo-femoral traction group and 17 degrees (range 8 degrees-44 degrees) in
      the control group (P = 0.017); postoperative averaged 6 degrees (range 1 degrees
      23 degrees) in the halo-femoral traction group and 7 degrees (range 0 degrees-27
      degrees) in the control group. Average pelvic obliquity correction was 78% in the
      halo-femoral traction group and 52% in the control group (P = 0.001). There were
      no intraoperative or postoperative halo-femoral traction apparatus-related
      complications noted (pin cut-out, femoral fractures, pin-sight infections, etc.).
      CONCLUSIONS: Intraoperative use of halo-femoral traction during the surgical
      treatment of patients with nonambulatory neuromuscular scoliosis provided
      significantly improved lumbar curve and pelvic obliquity correction.
      Intraoperative halo-femoral traction had no associated perioperative
      complications.

PMID- 16985469
TI  - Anterior/posterior spinal instrumentation versus posterior instrumentation alone
      for the treatment of adolescent idiopathic scoliotic curves more than 90 degrees.
AB  - STUDY DESIGN: A retrospective review of patients with adolescent idiopathic
      scoliosis (AIS), with curves more than 90 degrees treated with either a combined
      anterior/posterior spinal fusion or a posterior spinal fusion alone. OBJECTIVES:
      To assess the results of spinal fusion for AIS curves >90 degrees and determine
      whether the use of a posterior-only approach with an all-pedicle screw construct
      can decrease the need for anterior release surgery. SUMMARY OF BACKGROUND DATA:
      Treatment of AIS curves >90 degrees often consists of anterior release and
      posterior fusion to improve coronal correction and fusion rate. However, the use
      of pedicle screws has allowed improved coronal curve correction rates even in
      large curves, which may decrease the need for anterior release surgery. METHODS:
      A total of 54 consecutive patients with AIS with curves >90 degrees who underwent
      a spinal fusion procedure at 1 institution between 1987 and 2001, with either a
      combined anterior/posterior spinal fusion (hooks and screws) or a posterior
      spinal fusion alone with an all-pedicle screw construct, were included for
      analysis. All patients had a minimum 2-year follow-up (mean 6.0; range 2.0-14.5),
      and were analyzed radiographically as well as with pulmonary function tests.
      Statistical analyses were performed between groups using the Wilcoxon-Mann
      Whitney tests. RESULTS: There were 20 patients treated with an anterior/posterior
      spinal fusion and 34 with a posterior spinal fusion alone. There were no
      statistically significant differences between the groups for gender, age, number
      of levels fused, preoperative coronal/sagittal Cobb measurements, coronal curve
      flexibility, or amount of postoperative coronal Cobb correction. There was less
      of a negative effect on pulmonary function in the group treated with posterior
      spinal fusion versus the group treated with a combined anterior/posterior spinal
      fusion (P < 0.005). There were no complications/reoperations in either group.
      CONCLUSION: In this patient population with often restrictive preoperative
      pulmonary function, a posterior-only approach with the use of an all-pedicle
      screw construct has the advantage of providing the same correction as an
      anterior/posterior spinal fusion, without the need for entering the thorax and
      more negatively impacting pulmonary function.

PMID- 16985470
TI  - Comparison of pelvic fixation techniques in neuromuscular spinal deformity
      correction: Galveston rod versus iliac and lumbosacral screws.
AB  - STUDY DESIGN: Retrospective radiographic and clinical review. OBJECTIVE: To
      evaluate the safety and efficacy of iliac screws as a method of pelvic fixation
      in neuromuscular spinal deformity correction using the Galveston rod technique as
      a comparison group. SUMMARY OF BACKGROUND DATA: Sacropelvic fixation in patients
      with neuromuscular spinal deformity has traditionally used Galveston rods placed
      into the iliac wing. Difficulties with radiographic halos around the rods
      (loosening), rod contouring, and attaching to lumbar spine anchors have prompted
      their replacement with iliac screws. METHODS: A minimum 2-year radiographic and
      clinical follow-up compared 20 patients with the Galveston technique to 20
      patients with an iliac screw undergoing posterior spinal fusion (T2/T3-pelvis)
      for neuromuscular spinal deformity. All patients with the Galveston technique had
      sublaminar wires for their lumbar anchors, while the majority of patients with an
      iliac screw technique had at least 2 lumbar and/or sacral screws placed in
      addition to the iliac screws. RESULTS: There were no significant differences
      between the 2 groups in preoperative, postoperative, and latest follow-up (mean
      3.1 years) measurements for coronal Cobb measures, coronal and sagittal C7
      plumblines, and T1 offset. Pelvic obliquity was similar in both groups
      preoperatively (22 degrees) but at latest follow-up was statistically improved in
      the patients with an iliac screw (4.4 degrees) versus those with the Galveston
      technique (7.3 degrees) (P = 0.04). There were 13 patients with the Galveston
      technique versus 6 with an iliac screw who had radiolucent halos more than 2 mm
      around the pelvic anchor devices at latest follow-up (P < 0.05). The Galveston
      technique group had 4 broken rods and 2 reoperations, while the iliac screw group
      had 1 broken screw and no reoperations. CONCLUSIONS: Using iliac screws for
      pelvic fixation in neuromuscular spinal deformity affords equivalent maintenance
      of pelvic obliquity and scoliosis correction compared to the Galveston technique.
      Furthermore, the iliac screw technique avoids complex, lumbosacral 3-dimensional
      rod bends and yields minimal implant complications.

PMID- 16985472
TI  - Selective posterior thoracic fusions for adolescent idiopathic scoliosis:
      comparison of hooks versus pedicle screws.
AB  - STUDY DESIGN: A retrospective review of adolescent idiopathic scoliosis (AIS)
      patients with major thoracic-compensatory lumbar C modifier curves treated with a
      selective posterior fusion using an all-hook construct versus pedicle screw
      construct. OBJECTIVES: To compare the clinical and radiographic results of
      selective posterior thoracic fusion using hooks versus pedicle screws in patients
      with major thoracic-compensatory lumbar C modifier AIS curves. SUMMARY OF
      BACKGROUND DATA: Although spontaneous lumbar curve correction often occurs
      following a selective thoracic spinal fusion, there are few reports that focus on
      selective posterior thoracic spinal fusion in the presence of a lumbar C modifier
      curve. METHODS: Sixty-six consecutive patients with major thoracic-compensatory
      lumbar C modifier AIS curves underwent selective posterior thoracic fusion to T12
      or L1 at a single institution (1987-2001). Hooks were used for instrumentation in
      32 patients and pedicle screws were used in 34 patients. Patients were evaluated
      at a minimum 2-year follow-up. To test for differences between groups analysis of
      covariance (ANCOVA) was used. RESULTS: There was no statistical difference
      between the preoperative thoracic and lumbar Cobb values for the hook group
      versus the pedicle screw group. The amount of correction obtained surgically of
      the thoracic Cobb and the amount of spontaneous lumbar Cobb correction were
      significantly greater in the pedicle screw group (P < 0.001). The incidence of
      postoperative coronal decompensation, with a greater than 20 mm shift to the left
      of the C7 plumbline, was higher in the hook group (13 patients) as compared with
      the pedicle screw Group 4 patients (P < 0.005). There were no complications or
      reoperations in either group. CONCLUSION: Selective thoracic fusion of main
      thoracic-compensatory lumbar C modifier AIS curves with pedicle screws allowed
      for better thoracic correction and less postoperative coronal decompensation than
      seen with hooks.

PMID- 16985473
TI  - Re: Goldby LJ, Moore AP, Doust J, Trew ME. A randomised controlled trial
      investigating the efficiency of musculoskeletal physiotherapy on chronic low back
      disorder. Spine 2006;31:1083-93.

PMID- 16985474
TI  - Re: Goldby LJ, Moore AP, Doust J, et al. A randomized control trial investigating
      the efficiency of musculoskeletal physiotherapy on chronic back pain disorder.
      Spine 2006;31:1083-93.

PMID- 16985476
TI  - Re: Gutke A, Ostgaard HC, Oberg B. Pelvic girdle pain and lumbar pain in
      pregnancy: a cohort study of the consequences in terms of health and functioning.
      Spine 2006;31:E149-55.

PMID- 16985477
TI  - Granular myringitis: Incidence and clinical characteristics.
AB  - OBJECTIVE: To examine the incidence and the clinical features of granular
      myringitis (GM). STUDY DESIGN: A 2-year prospective cohort study. SETTING: A
      primary otolaryngology clinic affiliated with a tertiary academic referral
      center. PATIENTS: All-aged patients diagnosed with GM who had no apparent middle
      ear disease or did not undergo ear surgery. INTERVENTION: Otoscopy and
      bacteriologic and histopathologic studies. MAIN OUTCOME MEASURES: Granular
      myringitis was noted in 0.41% of patient's population presenting different forms.
      RESULTS: Granular myringitis was detected in 26 patients. Recurrent infection
      occurred in seven (26.9%) and bilateral GM in five patients (19.2%). Perforation
      of the tympanic membrane (TM) was noted in eight patients (30.7%), six of which
      closed spontaneously. Otoscopic findings could be classified into three grades:
      focal de-epithelization (in 10), focal polypoid granulations (in 13), and diffuse
      polypoid formation over the entire TM (in 3). Histopathologic examination
      disclosed tiny fragments of granulation tissue infiltrated by nonspecific chronic
      and acute inflammatory reaction. CONCLUSION: Granular myringitis is encountered
      not infrequently in primary otolaryngology practice and presented different
      forms, recurrent episodes, and bilateral involvement. Topical application of
      antibiotics or caustic agents was successful in all cases. Perforation of the TM
      may develop and resolve spontaneously during the course of the disease.

PMID- 16985478
TI  - Surgical findings and long-term hearing results in 3,050 stapedotomies for
      primary otosclerosis: a prospective study with the otology-neurotology database.
AB  - OBJECTIVE: To evaluate with a new otologic database the results of primary stapes
      surgery for otosclerosis with up to 14 years of follow-up in a consecutive series
      of 2,525 patients operated on by the same surgeon with the same technique
      (stapedotomy and vein graft interposition) and to provide online access to the
      complete data of this study for the reviewers. To study the effect of specific
      operative findings (obliterative otosclerosis and simultaneous malleus ankylosis)
      and age at the time of surgery on the long-term outcome. STUDY DESIGN:
      Prospective clinical study using a new computerized otologic database. SETTING: :
      Tertiary referral center. PATIENTS: Two thousand five hundred twenty-five
      patients who underwent 3,050 stapedotomies for otosclerotic stapes fixation were
      enrolled in this study from January 1991 to December 2004. Separate analyses were
      made for two unique pathologies (92 cases of obliterative otosclerosis and 19
      cases of simultaneous malleus ankylosis) diagnosed during surgery and for
      patients in two age brackets (<or=18 yr [28 patients] and >or=65 yr [302
      patients]). INTERVENTION: Stapedotomy with vein graft interposition and
      reconstruction with either a Teflon piston, a bucket handle prosthesis, or a
      total prosthesis. MAIN OUTCOME MEASURES: Preoperative and postoperative
      audiometric evaluation using conventional audiometry. Air-bone gap (ABG), bone
      conduction thresholds, and air-conduction thresholds were all assessed.
      Postoperative audiometry was performed at 3, 6, 9, 12, 18, and 24 months and then
      annually for 14 years. RESULTS: Overall, the postoperative ABG was closed to 10
      dB in 94.2% of cases. The mean four-frequency postoperative ABG was 1.7 dB
      compared with 25.6 dB preoperatively. The mean four-frequency bone-conduction
      thresholds were unchanged postoperatively. A significant postoperative
      sensorineural hearing loss (SNHL; >15 dB) was seen in 0.5% of cases in this
      series. Postoperative ABG was achieved to within 10 dB in 95% of cases of
      obliterative otosclerosis and in 64.7% of cases of simultaneous malleus
      ankylosis. A significant postoperative SNHL (>15 dB) was seen in 4.8% of cases of
      obliterative otosclerosis and was not observed in any cases of simultaneous
      malleus ankylosis. Postoperative ABG was achieved to within 10 dB in 93.5% of
      cases in the pediatric series and in 94.5% of cases in the senior series. A
      significant postoperative SNHL (>15 dB) was seen in 0.7% of cases in the senior
      group but was not observed in the children. CONCLUSION: Using a new otologic
      database, our series confirms that stapedotomy with vein graft interposition for
      otosclerotic stapes fixation is a safe and successful treatment for long-term
      hearing improvement. The deterioration in hearing with time after stapedotomy did
      not exceed the rate of hearing loss because of presbyacusis. Therefore, argon
      laser stapedotomy with vein graft interposition is our preferred surgical
      technique in the treatment of otosclerosis. Obliterative otosclerosis and
      simultaneous malleus ankylosis may be encountered during stapedotomy. Our study
      shows that reasonable success rates can still be expected in these situations.
      Stapedotomy results in the elderly and in children are comparable to those
      obtained in patients of other groups of age undergoing surgery for otosclerosis
      without an increased risk for complications.

PMID- 16985479
TI  - Quality-of-life assessment of Meniere's disease patients after surgical
      labyrinthectomy.
AB  - OBJECTIVE: To examine the impact of surgical labyrinthectomy on quality of life
      of Meniere's disease patients. STUDY DESIGN: Cross-sectional survey. SETTING:
      Otology subspecialty referral center. PATIENTS: All patients with Meniere's
      disease who underwent surgical labyrinthectomy between 1998 and 2004 were
      selected. Fifty-three patients satisfied inclusion criteria. Completed
      questionnaires were obtained from 44 patients. INTERVENTION(S): The Meniere's
      Disease Outcomes Questionnaire is a disease-specific quality-of-life
      questionnaire. It was used to assess the quality of life of patients before and
      after surgical labyrinthectomy. The questionnaire encompasses physical, mental,
      and social well-being domains of quality of life. MAIN OUTCOME MEASURE(S): Change
      in total quality-of-life score was used to assess the overall impact of surgical
      labyrinthectomy on subjective patient outcome. Individual quality-of-life domains
      were also assessed. RESULTS: Forty-three of 44 respondents (98%) had improvement
      in total score after surgery. The one patient who demonstrated deterioration
      developed latent contralateral disease. Average preoperative and postoperative
      scores were 34 +/- 14 and 67 +/- 15, respectively (p < 0.001). All questions
      showed significant improvement with surgery (p < 0.001) except questions
      pertaining to memory (no change) and hearing loss (nonsignificant decrease in
      score). CONCLUSION: This study comprises the first patient-directed assessment of
      quality-of-life outcomes in Meniere's disease patients after labyrinthectomy.
      Despite the disadvantage of hearing loss, patients consistently reported
      significant improvement in all quality-of-life domains and do not report a
      significant loss of quality of life in terms of their hearing loss. Surgical
      labyrinthectomy remains a highly effective treatment for Meniere's disease
      patients.

PMID- 16985480
TI  - Be a best-in-class organization.

PMID- 16985481
TI  - Effects of different dietary fatty acid supplements upon lipoprotein metabolism
      and lipid peroxides production in hyperlipidemic rats.
AB  - It has been well documented that hypercholesterolemia represents both a common
      and a dominant, although non-obligatory, risk factor in the progression of
      atherosclerosis. Research was conducted upon experimentally induced
      hyperlipidemic animals by means of a custom-tailored atherogenic diet. Cell
      susceptibility to nonenzyme-induced oxidative stress appears to be influenced by
      membrane fatty acid composition. This study was undertaken to determine whether
      differences in lipid peroxidation in steady-state and induced lipid peroxidation
      is a result of a different fatty acid supplementation. Adult Wistar strain rats
      of male gender were exposed to an atherogenic diet for a period of 160 days,
      before randomization into 6 dietary groups with different intragastral oil
      supplementation. Lipid peroxidation products were measured in 2.5% (w/v) of fresh
      liver homogenates (Tris-HCl, pH 7.4), by the assay of a thiobarbituric acid
      reactive substances (TBARS) formation using the procedures described by Okhawa
      (1979), including modifications (1989) in three different experimental
      conditions: steady-state (which corresponds to concentration of lipid peroxides
      in vivo ), spontaneous and metal-stimulated lipid peroxidation. Results were
      expressed as nmol TBARS per g of liver homogenate, calculated from the absorbency
      at 532 nm, using TEP as an external standard. This study shows that prolonged
      atherogenic dietary treatment causes moderate hypercholesterolemia and enhanced
      hypertriglyceridemia (+34.1% and +114.8, p < 0.001, respectively). Despite the
      lowering effects of the lipoprotein profiles, resulting from a fatty acid
      supplementation, at the end of each supplementation period, omega-6 fatty acids
      (soybean and corn oil) revealed an enhancement in the production of lipid
      peroxides (TBARS formation) measured in steady-state levels (+22.9%, p < 0.05 and
      +22.6%, p < 0.05, respectively). When liver homogenates were exposed to Fe2+ and
      ascorbic acid-induced oxidative stress, lipid peroxidation (LPO) was enhanced in
      the group treated with soybean oil (omega-6) and fish oil (omega-3; +48.4 %, p <
      0.001 and +44.1%, p < 0.001, respectively), but not in the group receiving corn
      oil. The achieved results support the hypothesis that the process of lipid
      peroxidation is not always in correlation with the number of double bonds in
      fatty acids esterified in phospholipid molecules. Consequently, it can be
      concluded that supplementation of unsaturated fatty acids, in the therapy of
      cardiovascular diseases, should include the administration of antioxidants, in
      order to prevent fatty acid decomposition in the case of oxidative insult.

PMID- 16985482
TI  - The frequency of insulin resistance calculated upon the basis of a fasting
      glucose to insulin ratio and characteristics of insulin resistant women with
      polycystic ovary syndrome.
AB  - BACKGROUND: The Polycystic Ovary Syndrome (PCOS) is a common endocrine and
      metabolic disorder of women of reproductive age, characterized by
      hyperandrogenism and chronic anovulation. Peripheral insulin resistance (IR) has
      a crucial role in the pathogenesis of this disorder. A fasting glucose to insulin
      (G/I) ratio is a simple, reliable, sensitive and specific measurement of insulin
      sensitivity and is a useful test for the identification of IR in women with PCOS,
      who have to be treated with insulin sensitizers. OBJECTIVE: To calculate the
      frequency of IR among patients with PCOS, using the fasting G/I ratio, and to
      compare the clinical and biochemical parameters between insulin-resistant and
      insulin-sensitive groups. PATIENTS AND METHODS: The study comprised 62 patients
      of reproductive age (18-40) with PCOS. The diagnosis PCOS was determined
      according to the diagnostic criteria from Rotterdam 2003, i.e. the presence of
      two of the following three criteria: oligo-ovulation and/or anovulation; clinical
      and/or biochemical hyperandrogenism; and polycystic ovaries. All other states
      associated with hyperandrogenism had been previously excluded. An inclusion
      criterion for the study was the body mass index (BMI) >or=25 (kg/m2). After
      calculating the fasting glucose(mg/dl) / insulin(microU/ml) ratio, the patients
      were separated in two groups, i.e. an insulin-resistant group with a fasting G/I
      ratio of < 4.5(mg/10(-4) U) and an insulin-sensitive group with a fasting G/I
      ratio of >/=4.5(mg/10(-4) U). RESULTS: In our study, 58.06% of women with PCOS
      and BMI >or=25 (kg/m2) were insulin-resistant. There was no significant
      difference between the two groups in age or BMI. Sex hormone binding globulin
      (SHBG) levels were significantly lower in the insulin-resistant group (17.83 +/-
      8.38 vs. 42.66 +/- 27.65 (nmol/l); p=0.0036) and they had a higher free
      testosterone index (19.38 +/- 8.91 vs. 9.55 +/-3.51(%); p=0.001) in comparison
      with the insulin-sensitive group. Progesterone levels were significantly lower in
      the IR group (2.41 +/- 2.50 vs. 7.05 +/- 8.04 (ng/ml); p=0.034). CONCLUSION: A
      fasting glucose to insulin ratio is a simple and useful test for identifying
      insulin-resistant obese women with PCOS. SHBG and progesterone (oligo
      ovulation/anovulation) can be useful markers for long-term health risks in women
      with PCOS (diabetes mellitus type 2 and cardiovascular diseases). In this way we
      could identify the group of PCOS subjects and its subgroups, which would benefit
      from therapy with insulin sensitizers, with respect to the reduction of risks of
      chronic complications.

PMID- 16985483
TI  - Initial empiric antimicrobial treatment of Chlamydia pneumoniae: a study of 54
      cases in the Republic of Macedonia.
AB  - Analysis of the adequacy of the initial empiric antimicrobial treatment of
      patients with acute Chlamydia pneumoniae (CP) infection, admitted to the
      Infectious Diseases Clinic, Clinical Centre, Medical Faculty, Skopje, Republic of
      Macedonia, for community-acquired pneumonia. MATERIAL AND METHODS: A total number
      of 407 patients with community-acquired pneumonia (CAP) hospitalized at the
      Clinic between September 1997 and June 2002, with an average age of x=46.44
      years, of whom 53.56% were male. Acute Chlamydia pneumoniae infection was proven
      serologically with MIF assay in 54 (13.27%) patients. RESULTS: Initial empiric
      treatment with antibiotics in patients with CP pneumonia was provided with
      antimicrobial agents with intracellular activity in 26 (48.15%) patients; with
      fluoroquinolones in 19 (35.19%); macrolides in 5 (9.26%) and tetracyclines in 2
      (3.7%). The treatment was conducted as monotherapy in 6 patients (11.11%) and in
      20 patients (37.04%) in combination with betalactams. For 28 (51.85%) patients
      who were treated only with betalactams, empiric treatment was re-evaluated and
      new therapy with fluoroquinolon was conducted in 16 (29.63%), with macrolides in
      8 (14.81%) and with tetracyclines in 4 (7.41%) patients. CONCLUSION: Adequate
      empiric treatment with antimicrobial agents with intracellular activity was
      performed in only 48.15% of the patients with acute CP infection. Therefore, when
      designing the initial empiric treatment of patients hospitalized with pneumonia,
      attention should be paid to this atypical pathogen of CAP.

PMID- 16985484
TI  - Association of patients with parkinsonism and epilepsy with EEG changes.
AB  - EEG is an important diagnostic method for epilepsies. EEG changes in patients
      with Parkinson's disease and epilepsy are not unknown or unexpected events. We
      investigated 250 Parkinson's disease patients. Epileptic seizures were recorded
      in 10 patients. Four patients had generalized tonic clonic seizures; 3 partial
      complex seizures, 2 of which with secondary generalization; while 3 patients had
      right-handed simple motor partial seizure. Clinical and neurophysiological
      investigations, neuroimagining techniques electroencephalographic investigations
      (EEG, EEG in sleep) were conducted. Our patients were well controlled with
      antiepileptic therapy.

PMID- 16985485
TI  - Induction of atrioventricular node reentry by simultaneous anterograde conduction
      over the fast and slow pathways.
AB  - Atrio-ventricular node reentry (AVNRT) is typically induced with an anterograde
      block over the fast pathway (FP) and conduction over the slow pathway (SP), with
      subsequent retrograde conduction over the FP. Rarely, a premature atrial complex
      (PAC) conducts simultaneously over the FP and SP to induce AVNRT. Previous
      publications have reported that conduction over the fast and slow pathway of the
      atrioventricular node can occur successively one after the other, thus leading to
      dual ventricular depolarization from what initially was a single atrial impulse.
      We report a case of an 18-year-old male patient referred for repeated bursts of
      ectopic activity. Evaluation of the patient's electrocardiographic recordings
      suggested the presence of dual ventricular activations for each atrial beat. The
      electrophysiological study revealed that the patient had simultaneous conduction
      over the fast and slow pathways of the atrioventricular node giving rise to a non
      reentrant tachycardia, along with an absence of retrograde (ventriculoatrial)
      conduction, and a significant atrio-His bundle jump (A-H jump) through the slow
      pathway from the fast pathway during programmed electrical stimulation from the
      right atrium. Ablation of the slow pathway at the base of the Koch triangle
      yielded a cessation of the dual ventricular response, absence of the nonreentrant
      tachycardia and no A-H jump.

PMID- 16985486
TI  - Operative treatment of III grade open fractures of the tibial diaphysis.
AB  - Open fractures, especially III grade open fractures of the tibial diaphysis,
      according to the Gustilo classification still remains a serious therapeutic
      problem. The aim of the study was to evaluate the clinical results after
      operative treatment of III grade open fractures of diaphysis of the tibia and to
      promote a new method of fracture fixation. MATERIAL AND METHODS: 48 patients with
      open fractures of the tibial diaphysis, classified as type III A and B, according
      to the Gustilo classification, were operatively treated. Patients were divided
      into two groups depending on the manner of fracture fixation. Patients in group A
      (30 pts.) were treated with an external fixator and those in group B (18 pts.)
      with unreamed intramedullary nails. The time of the union of the fracture,
      problems with the union (malunion and nonunion), infection, different
      complications and the functional outcome were examined. Late complications and
      their treatment were not the object of the study. The follow-up period was at
      least 12 months. The results of the study showed a mean time of union of 38.4
      weeks in patients in group A, and 32.8 for those in group B. Malunion was noticed
      in 5 (16.6%) in group A and 2 (11.1%) in group B, nonunion in 4 (13.35) in group
      A and in 2 (11.1%) patients in group B. Superficial infection developed in 7
      (23.3%) and deep in 6 (20%) of the patients in group A and in group B in 4
      (22.2%) and 2 (11.1%) of the patients. Results from the functional examination
      showed 26.6% excellent and the same percent of fair results in group A. In group
      B there were 55.5% excellent and 11.1% fair results. Different types of
      complications were noticed in the patients from both groups. The final results of
      the examination showed a shorter time of union, a lower percentage of
      complications and a better functional outcome in the patients in group B.
      Unreamed intramedullary interlocking nailing of open fractures of the diaphysis
      of the tibia (grade III A and B according Gustilo classification) is a relatively
      safe method of operative treatment with fewer complications compared with
      external fixation.

PMID- 16985487
TI  - Inflammation predicts all-cause and cardiovascular mortality in haemodialysis
      patients.
AB  - Among non-traditional cardiovascular risk factors both malnutrition and
      inflammation appear to be strong predictors of mortality and morbidity in
      haemodialysis (HD) patients. Our study objective was to determine predictors of
      all-cause and cardiovascular mortality, considering the nutritional and
      immunologic parameters, in a cohort of HD patients treated in a single
      haemodialysis centre. 216 patients on HD were analyzed for clinical, nutritional
      serum albumen and BMI, immunologic-serum CRP (C-reactive protein) and fibrinogen
      and dialysis parameters -- ultrafiltration, length of dialysis in hours, HD dose
      (using spKt/V and eKt/V). Mortality was monitored prospectively over a two-year
      period. Fifty-five of the 216 HD patients died during the follow-up period and
      the main cause of death was cardiovascular disease (CVD) -- 33 patients out of 55
      (60%), followed by infection/sepsis (13 pts, 24%). The patients who died were
      significantly older, had a significantly shorter duration of HD in hours,
      ultrafiltration was significantly less, HD doses were significantly lower, as
      were serum levels of albumin (36.06 +/- 4.17 vs. 39.74 +/- 3.31; p=0.000) and Hg
      (93.14 +/- 15.43 vs. 109,16 +/- 12,08; p=0.000), but they had significantly
      higher serum levels of CRP (40.26 +/- 34.75 vs. 8.71 +/- 7.68, p=0.000) and
      fibrinogen (5.28 +/- 1.28 vs. 4.42 +/- 0.97, p=0.000). Kaplan-Meier survival
      estimates showed that the group with the lowest levels of albumin (< 3.5 g/L),
      and with the greatest levels of CRP (>20 mg/l) and fibrinogen (>5 g/L) had the
      lowest survival (log-rank test p=0.0008, p=0.00000, p=0.0000). However, in the
      Cox proportional hazards model, a high CRP and low Hg level (chi-square=96.467,
      p=0.0000) were predictors of all-cause mortality, whereas serum level of albumin
      did not show to be predictive. When only cardiovascular mortality is entered into
      the Cox model, CRP and Hg levels are still more important in predicting mortality
      (chi-square=70.055, p=0.0000) and only if CRP is not taken into account in the
      multivariate analysis, serum albumin level remains, after Hg, the strongest
      predictor for both overall and cardiovascular mortality (chi-square=76,564,
      p=0.0000; chi-square 50.619 p=0.0000). It can be concluded that inflammation
      predicted all-cause and cardiovascular mortality in our study group, because high
      CRP, as a marker of inflammation and low haemoglobin, as a result of
      inflammation, remained powerful predictors of both overall and cardiovascular
      death.

PMID- 16985488
TI  - Successful treatment of soft tissue calcifications in uremia.
AB  - The appearance of soft tissue calcifications in patients with chronic renal
      failure has been recognised as one of the serious complications of uremia. An
      elevated serum calcium-phosphate product has almost invariably been detected,
      although the exact mechanisms of precipitation are still not fully understood.
      Among the factors responsible for triggering the precipitation process are:
      hyperphosphatemia, secondary hyperparathyroidism, hypercalcemia, treatment with
      vitamin D3, etc. Phosphate binders have been used to prevent, among other things,
      soft tissue calcifications, and parathyroidectomy has most frequently been
      applied as the therapy of choice, once precipitation of calcium salts has
      occurred. We present a case of soft tissue calcifications in the gluteal regions
      of a chronic haemodialysis female patient. The therapy we chose was a combination
      of biphosphonate and deferoxamine. The patient was treated for two months. The
      regression of the soft tissue calcifications was very significant, as registered
      both clinically and radiologically. The exact mechanism by which this reversal
      was achieved needs further investigation.

PMID- 16985489
TI  - Journal quality and visibility: Is there a way out of the scientific periphery?
AB  - Scientific journals play an important role in the transfer of scientific
      information, and international visibility is a prerequisite for fulfilling this
      role. However, entering international bibliographic databases is a major
      challenge for the journals from the so-called scientific periphery. These
      journals have an unfavourable starting position because of the small number of
      manuscripts received, an insufficient pool of reviewers, the low quality of
      published articles, and poor international visibility, all of which reduce the
      pool of potential authors and close a "vicious circle of inadequacy". To break
      this circle, editors have to make a great effort to improve basic journal
      publishing standards, especially timeliness; to find a "niche" for their journal;
      to increase the international diversity of the Editorial Board; and to actively
      seek for authors and help them to improve the quality of their manuscripts. The
      example of the Croatian Medical Journal (Zagreb, Croatia) shows that it is
      possible to get out of the scientific periphery if editors have a clear vision
      and willingness to work really hard.

PMID- 16985490
TI  - Drugs for HIV infection.

PMID- 16985491
TI  - A matter of trust.
AB  - Recent instances of potential conflicts of interest involving authors and journal
      editors may tarnish public confidence in the integrity of science journals.

PMID- 16985492
TI  - A new web resource for NIH immunology.

PMID- 16985493
TI  - Life amidst the contrivances.
AB  - The established dogma of 'horror autotoxicus' was overturned 50 years ago with
      the publication of a paper showing that autoimmune thyroiditis could be induced
      in animals. Noel Rose recounts the events that led to the establishment of
      autoimmunity as a cause of disease.

PMID- 16985494
TI  - Stemming the tide of thymic aging.
AB  - The establishment and replenishment of thymic epithelium and the persistence of
      epithelial progenitor cells into adult life were discussed at ThymOz-V 2006.

PMID- 16985495
TI  - Deadly plague versus mild-mannered TLR4.

PMID- 16985496
TI  - Passera ou ne passera pas--accessibility is key.

PMID- 16985497
TI  - Hematopoietic stem cell biology: too much of a Wnt thing.

PMID- 16985498
TI  - DisSARMing Toll-like receptor signaling.

PMID- 16985500
TI  - On regulation of phagosome maturation and antigen presentation.
AB  - Phagocytosis has essential functions in immunity. Here we highlight the presence
      of a subcellular level of self-non-self discrimination in dendritic cells that
      operates at the level of individual phagosomes. We discuss how engagement of Toll
      like receptor signaling controls distinct programs of phagosome maturation. An
      inducible mode of phagosome maturation triggered by these receptors ensures the
      selection of microbial antigens for presentation by major histocompatibility
      class II molecules during the simultaneous phagocytosis of self and non-self.

PMID- 16985501
TI  - Novel deletion variants of 9q13-q21.12 and classical euchromatic variants of
      9q12/qh involve deletion, duplication and triplication of large tracts of
      segmentally duplicated pericentromeric euchromatin.
AB  - Large-scale copy number variation that is cytogenetically visible in normal
      individuals has been described as euchromatic variation but needs to be
      distinguished from pathogenic euchromatic deletion or duplication. Here, we
      report eight patients (three families and two individuals) with interstitial
      deletions of 9q13-q21.12. Fluorescence in situ hybridisation with a large panel
      of BACs showed that all the deleted clones were from extensive tracts of
      segmentally duplicated euchromatin, copies of which map to both the long and
      short arms of chromosome 9. The variety of reasons for which these patients were
      ascertained, and the phenotypically normal parents, indicates that this is a
      novel euchromatic variant with no phenotypic effect. Further, four patients with
      classical euchromatic variants of 9q12/qh or 9p12 were also shown to have
      duplications or triplications of this segmentally duplicated material common to
      both 9p and 9q. The cytogenetic boundaries between the segmentally duplicated
      regions and flanking unique sequences were mapped to 9p13.1 in the short arm (BAC
      RP11-402N8 at 38.7 Mb) and to 9q21.12 in the long arm (BAC RP11-88I18 at 70.3
      Mb). The BACs identified in this study should in future make it possible to
      differentiate between clinically significant deletions or duplications and
      euchromatic variants with no established phenotypic consequences.

PMID- 16985502
TI  - A recent genetic link between Sami and the Volga-Ural region of Russia.
AB  - The genetic origin of the Sami is enigmatic and contributions from Continental
      Europe, Eastern Europe and Asia have been proposed. To address the evolutionary
      history of northern and southern Swedish Sami, we have studied their mtDNA
      haplogroup frequencies and complete mtDNA genome sequences. While the majority of
      mtDNA diversity in the northern Swedish, Norwegian and Finnish Sami is accounted
      for by haplogroups V and U5b1b1, the southern Swedish Sami have other haplogroups
      and a frequency distribution similar to that of the Continental European
      population. Stratification of the southern Sami on the basis of occupation
      indicates that this is the result of recent admixture with the Swedish
      population. The divergence time for the Sami haplogroup V sequences is 7600 YBP
      (years before present), and for U5b1b1, 5500 YBP amongst Sami and 6600 YBP
      amongst Sami and Finns. This suggests an arrival in the region soon after the
      retreat of the glacial ice, either by way of Continental Europe and/or the Volga
      Ural region. Haplogroup Z is found at low frequency in the Sami and Northern
      Asian populations but is virtually absent in Europe. Several conserved
      substitutions group the Sami Z lineages strongly with those from Finland and the
      Volga-Ural region of Russia, but distinguish them from Northeast Asian
      representatives. This suggests that some Sami lineages shared a common ancestor
      with lineages from the Volga-Ural region as recently as 2700 years ago,
      indicative of a more recent contribution of people from the Volga-Ural region to
      the Sami population.

PMID- 16985503
TI  - Enhanced sensitivity to the euphoric effects of alcohol in schizophrenia.
AB  - The purpose of this study was to determine whether schizophrenia was associated
      with alterations in alcohol response that might explain the elevated risk for
      AUDs in this population. In a randomized, double-blind, placebo-controlled,
      counter-balanced 3 test day laboratory study, the effects of alcohol were
      compared in 23 subjects with schizophrenia (without any previous alcohol use
      disorder (AUD) but with some alcohol exposure) and in 14 healthy subjects matched
      for age, gender, education, and lifetime exposure to alcohol. Standard alcohol
      drinks in a scheduled design were administered to produce blood alcohol levels of
      0, 0.02-0.04 mg%, or 0.06-0.08 mg%. Schizophrenia symptoms, perceptual
      alterations, stimulant and depressant subjective effects of alcohol, and 'high'
      were measured before alcohol administration and at several post-drug time points.
      Verbal learning and recall, vigilance and distractibility, and motor function
      were assessed once per test day. Relative to healthy subjects, subjects with
      schizophrenia reported greater euphoria and stimulatory effects in response to
      alcohol. Alcohol produced small transient increases in positive psychotic
      symptoms and perceptual alterations without affecting negative symptoms. Alcohol
      also impaired several aspects of immediate and delayed recall, and vigilance, and
      distractibility. Schizophrenia patients showed increased euphoric and stimulatory
      responses to alcohol. These exaggerated positive responses to alcohol doses may
      contribute to the increased risk for AUDs associated with schizophrenia. The
      absence of 'beneficial' effects of alcohol does not support a self-medication
      hypothesis of alcohol use in schizophrenia.

PMID- 16985504
TI  - The role of caspase-3 activation in phencyclidine-induced neuronal death in
      postnatal rats.
AB  - This study determined the role of caspase-3 in phencyclidine (PCP)-induced
      neurodegeneration in postnatal rats. PCP administration to postnatal day 7 rats
      induced a dose-dependent increase in caspase-3 enzymatic activity in frontal
      cortex, striatum, and hippocampus. Enzymatic activation was present at 4 h,
      peaked between 6 and 12 h, and disappeared by 24 h. Further, cleaved caspase-3
      immunoreactive neurons were detected as early as 2 h in the cortex, and were
      found throughout the brain, including, in addition, the thalamus and striatum.
      Within the cingulate, frontal, parietal, and retrosplenial cortices,
      immunoreactivity was specific for layers II-IV (especially layer II). Neurons
      positive for both silver staining and terminal deoxynucleotidyl transferase
      biotin-d-UTP nick-end labeling (TUNEL) were found in the same brain regions and
      subregions. Double labeling experiments confirmed that cleaved caspase-3 and
      TUNEL were coexpressed in many neurons in all brain regions and subregions
      studied. Temporal studies revealed that procaspase-3 cleavage preceded TUNEL
      staining by about 3 h, with many neurons being positive for both caspase-3 and
      TUNEL 9 h after PCP treatment. In organotypic corticostriatal slices, PCP caused
      a concentration- and time-dependent cleavage of procaspase-3 that was also
      colocalized with TUNEL staining in layers II-IV of the parietal cortex. Caspase-3
      activation again preceded PCP-induced DNA damage assessed by TUNEL. PCP-induced
      neuronal death in vitro as measured by TUNEL staining was blocked 85% by Ac
      AAVALLPAVLLALLAPDEVD-CHO, a cell-permeable selective caspase-3 inhibitor. These
      data demonstrate that caspase-3 activation plays a necessary role in the
      regionally selective neuronal death induced by PCP in the developing rat brain.

PMID- 16985505
TI  - Growth factor-stimulated generation of new cortical tissue and functional
      recovery after stroke damage to the motor cortex of rats.
AB  - Recent studies suggest that proliferation in the adult forebrain subventricular
      zone increases in response to a forebrain stroke and intraventricular infusions
      of growth factors enhance this response. The potential for growth factor
      infusions to regenerate the damaged motor cortex and promote recovery of motor
      function after stroke has not been examined. Here, we report that
      intraventricular infusions of epidermal growth factor and erythropoietin
      together, but not individually, promote substantial regeneration of the damaged
      cerebral cortex and reverse impairments in spontaneous and skilled motor tasks,
      in a rat model of stroke. Cortical regeneration and functional recovery occurred
      even when growth factor administration was delayed for up to 7 days after the
      stroke-induced lesion. Cell tracking demonstrated the contribution of neural
      precursors originating in the forebrain subventricular zone to the regenerated
      cortex. Strikingly, removal of the regenerated cortical tissue reversed the
      growth factor-induced functional recovery. These findings reveal that specific
      combinations of growth factors can mobilize endogenous adult neural stem cells to
      promote cortical tissue re-growth and functional recovery after stroke.

PMID- 16985506
TI  - Brain trauma leads to enhanced lung inflammation and injury: evidence for role of
      P4504Fs in resolution.
AB  - Traumatic brain injury is known to cause several secondary effects, which lead to
      multiple organ dysfunction syndrome. An acute systemic inflammatory response
      seems to play an integral role in the development of such complications providing
      the potential for massive secondary injury. We show that a contusion injury to
      the rat brain causes large migration of inflammatory cells (especially
      macrophages and neutrophils) in the major airways and alveolar spaces at 24 h
      post-injury, which is associated with enhanced pulmonary leukotriene B4 (LTB4)
      production within the lung. However, by 2 weeks after injury, a temporal switch
      occurs and the resolution of inflammation is underway. We provide evidence that 5
      lipoxygenase and Cytochrome P450 4Fs (CYP4Fs), the respective enzymes responsible
      for LTB4 synthesis and breakdown, play crucial roles in setting the cellular
      concentration of LTB4. Activation of LTB4 breakdown via induction of CYP4Fs,
      predominantly in the lung tissue, serves as an endogenous signal to ameliorate
      further secondary damage. In addition, we show that CYP4Fs are localized
      primarily in the airways and pulmonary endothelium. Given the fact that adherence
      to the microvascular endothelium is an initial step in neutrophil diapedesis, the
      temporally regulated LTB4 clearance in the endothelium presents a novel focus for
      treatment of pulmonary inflammation after injury.

PMID- 16985507
TI  - Total cerebral blood flow estimated by color velocity imaging quantification
      ultrasound: a predictor for recurrent stroke?
AB  - Although the Virchow's triad on thrombosis includes reduced blood flow as a
      factor, there has been relatively little data on the importance of total cerebral
      blood flow on the risk of subsequent stroke. In the current study, we investigate
      whether total cerebral blood flow helps predict stroke recurrence. Extracranial
      arterial blood flow volume estimated by color velocity imaging quantification
      ultrasound (CVIQ) is an index of cerebral blood flow measurement. We performed a
      cohort study of 210 consecutive acute stroke patients. Patients were studied with
      transcranial Doppler and duplex ultrasound for intra- and extracranial large
      artery disease within 3 days of symptom onset. The association between the risk
      of recurrent stroke and CVIQ was analyzed with Cox proportional hazards model.
      Thirty-nine patients (17.7%) developed an ischemic stroke during a mean follow-up
      of 47.5 months. The mean extracranial blood flow volume was significantly lower
      for patients who had a recurrent stroke than those without (594.4+/-130.3 versus
      683.8+/-176.9 mL/min; P=0.003). In a Cox proportional hazards model adjusting for
      potential confounding variables, extracranial blood flow volume (hazard ratio
      (HR) for lowest tertile, 4.1; 95% confidence interval (CI), 1.5 to 11.0) along
      with male sex (HR, 2.5; 95% CI, 1.3 to 5.1), diabetes (HR, 2.5; 95% CI, 1.2 to
      5.0) and large artery stenosis (HR, 2.2; 95% CI, 1.1 to 4.4) were independent
      predictors for stroke recurrence. Our data indicated that patient with low amount
      of blood flow to the brain is at risk of recurrent stroke.

PMID- 16985508
TI  - Parasitism and the retrotransposon life cycle in plants: a hitchhiker's guide to
      the genome.
AB  - LTR (long terminal repeat) retrotransposons are the main components of higher
      plant genomic DNA. They have shaped their host genomes through insertional
      mutagenesis and by effects on genome size, gene expression and recombination.
      These Class I transposable elements are closely related to retroviruses such as
      the HIV by their structure and presumptive life cycle. However, the
      retrotransposon life cycle has been closely investigated in few systems. For
      retroviruses and retrotransposons, individual defective copies can parasitize the
      activity of functional ones. However, some LTR retrotransposon groups as a whole,
      such as large retrotransposon derivatives and terminal repeats in miniature, are
      non-autonomous even though their genomic insertion patterns remain polymorphic
      between organismal accessions. Here, we examine what is known of the
      retrotransposon life cycle in plants, and in that context discuss the role of
      parasitism and complementation between and within retrotransposon groups.

PMID- 16985509
TI  - Admixture in European Populus hybrid zones makes feasible the mapping of loci
      that contribute to reproductive isolation and trait differences.
AB  - The use of admixed human populations to scan the genome for chromosomal segments
      affecting complex phenotypic traits has proved a powerful analytical tool.
      However, its potential in other organisms has not yet been evaluated. Here, we
      use DNA microsatellites to assess the feasibility of this approach in hybrid
      zones between two members of the 'model tree' genus Populus: Populus alba (white
      poplar) and Populus tremula (European aspen). We analyzed samples of both species
      and a Central European hybrid zone (N=544 chromosomes) for a genome-wide set of
      19 polymorphic DNA microsatellites. Our results indicate that allele frequency
      differentials between the two species are substantial (mean delta=0.619+/-0.067).
      Background linkage disequilibrium (LD) in samples of the parental gene pools is
      moderate and should respond to sampling schemes that minimize drift and account
      for rare alleles. LD in hybrids decays with increasing number of backcross
      generations as expected from theory and approaches background levels of the
      parental gene pools in advanced generation backcrosses. Introgression from P.
      tremula into P. alba varies strongly across marker loci. For several markers,
      alleles from P. tremula are slightly over-represented relative to neutral
      expectations, whereas a single locus exhibits evidence of selection against P.
      tremula genotypes. We interpret our results in terms of the potential for
      admixture mapping in these two ecologically divergent Populus species, and we
      validate a modified approach of studying genotypic clines in 'mosaic' hybrid
      zones.

PMID- 16985510
TI  - The quantitative genetic basis of polyandry in the parasitoid wasp, Nasonia
      vitripennis.
AB  - Understanding the evolution of female multiple mating (polyandry) is crucial for
      understanding sexual selection and sexual conflict. Despite this interest, little
      is known about its genetic basis or whether genetics influences the evolutionary
      origin or maintenance of polyandry. Here, we explore the quantitative genetic
      basis of polyandry in the parasitoid wasp Nasonia vitripennis, a species in which
      female re-mating has been observed to evolve in the laboratory. We performed a
      quantitative genetic experiment on a recently collected population of wasps. We
      found low heritabilities of female polyandry (re-mating frequency after 18 h),
      low heritability of courtship duration and a slightly higher heritability of
      copulation duration. However, the coefficients of additive genetic variance for
      these traits were all reasonably large (CV(A)>7.0). We also found considerable
      dam effects for all traits after controlling for common environment, suggesting
      either dominance or maternal effects. Our work adds to the evidence that
      nonadditive genetic effects may influence the evolution of mating behaviour in
      Nasonia vitripennis, and the evolution of polyandry more generally.

PMID- 16985511
TI  - Gender differences in renal nuclear receptors and aryl hydrocarbon receptor in
      5/6 nephrectomized rats.
AB  - This study was aimed at delineating molecular pathways essential in gender
      different pathogenesis of chronic kidney diseases (CKD). Renal transcripts of
      nuclear receptors and metabolic enzymes in male and female kidneys from 5/6
      nephrectomized (Nx) rats 7 weeks post-Nx were examined using branched DNA signal
      amplification assay. Nx-males had marked kidney injury coupled with anemia and
      malnutrition. Nx-females had moderate renal injury, and were free of albuminuria,
      anemia, and malnutrition. Nx-males had systemic and renal inflammation, which
      were largely absent in Nx-females. Blood 17beta-estradiol, testosterone, and
      corticosterone did not change, whereas urinary testosterone decreased in both
      genders. Compared to males, female kidneys had higher androgen receptor (AR) and
      aryl hydrocarbon receptor (AhR) but lower estrogen receptor alpha (ERalpha).
      Compared to Nx-males, female remnant kidneys had less decreases in ERalpha and
      peroxisome proliferator-activated receptor alpha (PPARalpha), had no induction of
      AR and decrease of acyl-CoA oxidase, whereas had induction of cytochrome P450 4a1
      (Cyp4a1) but decrease of AhR. Renal protein expression of a 52-kDa isoform of
      Wilm's tumor 1 (WT1), transcription factor critical in nephrogenesis, decreased
      dramatically in Nx-males but largely preserved in Nx-females. In conclusion,
      gender divergences in basal expression and alteration of ERalpha, AR, AhR, WT1,
      and PPARalpha/Cyp4a1 during CKD may explain gender differences in CKD progression
      and outcome of renal transplantation.

PMID- 16985512
TI  - Local delivery of angiotensin receptor blocker into the kidney ameliorates
      progression of experimental glomerulonephritis.
AB  - Intrarenally synthesized angiotensin II (Ang II) may be involved in the
      progression of glomerulonephritis, leading to irreversible glomerulosclerosis.
      There is increasing evidence that systemic angiotensin receptor blocker (ARB)
      treatment has beneficial effect on the prognosis of progressive
      glomerulonephritis and diabetic nephropathy. However, the cellular and molecular
      mechanisms behind this therapeutic effect of ARB remain unclear. In this study,
      we used a novel strategy of local ARB delivery via type-1 collagen sponge, to
      treat progressive glomerulonephritis that would result in irreversible
      glomerulosclerosis in our previously established rat model. At days 9 and 14
      after disease induction, mild proteinuria, 20.7+/-4.7 and 10+/-1.3 mg/day, was
      found. Local ARB treatment reduced proteinuria significantly to 3.19+/-3.2 and
      5.25+/-0.95 mg/day (P < 0.01), respectively. Scoring of glomerular matrix
      expansion and sclerotic index revealed that local ARB treatment significantly
      ameliorated glomerular pathology. Ang II type 1 receptor mRNA expression was
      remarkably enhanced in the Ang II group and ARB treatment reversed this effect at
      14 days. Local delivery of ARB significantly improved glomerular blood flow
      levels, compared to the untreated disease control group, from 710+/-18.25 to
      859.44+/-22.86 microm/s, respectively. Local delivery of ARB into the kidney
      affected local RAS and thus improved the renal injury and function in the
      potentially progressive glomerulosclerosis of rat model.

PMID- 16985513
TI  - Reactive oxygen species and nuclear factor-kappa B pathway mediate high glucose
      induced Pax-2 gene expression in mouse embryonic mesenchymal epithelial cells and
      kidney explants.
AB  - Diabetic mellitus confers a major risk of congenital malformations, and is
      associated with diabetic embryopathy, affecting multiple organs including the
      kidney. The DNA paired box-2 (Pax-2) gene is essential in nephrogenesis. We
      investigated whether high glucose alters Pax-2 gene expression and aimed to
      delineate its underlying mechanism(s) of action using both in vitro (mouse
      embryonic mesenchymal epithelial cells (MK4) and ex vivo (kidney explant from
      Hoxb7-green florescent protein (GFP) mice) approaches. Pax-2 gene expression was
      determined by reverse transcriptase-polymerase chain reaction, Western blotting,
      and immunofluorescent staining. A fusion gene containing the full-length 5'
      flanking region of the human Pax-2 promoter linked to a luciferase reporter gene,
      pGL-2/hPax-2, was transfected into MK4 cells with or without dominant negative
      IkappaBalpha (DN IkappaBalpha) cotransfection. Fusion gene expression level was
      quantified by cellular luciferase activity. Reactive oxygen species (ROS)
      generation was measured by lucigenin assay. Embryonic kidneys from Hoxb7-GFP mice
      were cultured ex vivo. High D(+) glucose (25 mM), compared to normal glucose (5
      mM), specifically induced Pax-2 gene expression in MK4 cells and kidney explants.
      High glucose-induced Pax-2 gene expression is mediated, at least in part, via ROS
      generation and activation of the nuclear factor kappa B signaling pathway, but
      not via protein kinase C, p38 mitogen-activated protein kinase (MAPK), and p44/42
      MAPK signaling.

PMID- 16985514
TI  - The connecting tubule is the main site of the furosemide-induced urinary
      acidification by the vacuolar H+-ATPase.
AB  - Final urinary acidification is achieved by electrogenic vacuolar H(+)-ATPases
      expressed in acid-secretory intercalated cells (ICs) in the connecting tubule
      (CNT) and the cortical (CCD) and initial medullary collecting duct (MCD),
      respectively. Electrogenic Na(+) reabsorption via epithelial Na(+) channels
      (ENaCs) in the apical membrane of the segment-specific CNT and collecting duct
      cells may promote H(+)-ATPases-mediated proton secretion by creating a more lumen
      negative voltage. The exact localization where this supposed functional
      interaction takes place is unknown. We used several mouse models performing renal
      clearance experiments and assessed the furosemide-induced urinary acidification.
      Increasing Na(+) delivery to the CNT and CCD by blocking Na(+) reabsorption in
      the thick ascending limb with furosemide enhanced urinary acidification and net
      acid excretion. This effect of furosemide was abolished with amiloride or
      benzamil blocking ENaC action. In mice deficient for the IC-specific B1 subunit
      of the vacuolar H(+)-ATPase, furosemide led to only a small urinary
      acidification. In contrast, in mice with a kidney-specific inactivation of the
      alpha subunit of ENaC in the CCD and MCD, but not in the CNT, furosemide alone
      and in combination with hydrochlorothiazide induced normal urinary acidification.
      These results suggest that the B1 vacuolar H(+)-ATPase subunit is necessary for
      the furosemide-induced acute urinary acidification. Loss of ENaC channels in the
      CCD and MCD does not affect this acidification. Thus, functional expression of
      ENaC channels in the CNT is sufficient for furosemide-stimulated urinary
      acidification and identifies the CNT as a major segment in electrogenic urinary
      acidification.

PMID- 16985515
TI  - Renal injury due to renin-angiotensin-aldosterone system activation of the
      transforming growth factor-beta pathway.
AB  - Glomerulosclerosis, interstitial fibrosis, and tubular atrophy occur with end
      stage kidney failure, irrespective of the primary etiology. The transforming
      growth factor-beta (TGF-beta) is a key factor in these alterations either
      directly, by stimulating synthesis of extracellular matrix components and
      reducing collagenase production, or indirectly through other profibrogenic
      factors such as connective tissue growth factor (CTGF). TGF-beta is important for
      the proliferation of intrarenal fibroblasts and the epithelial-mesenchymal
      transition through which tubular cells become fibroblasts. Although several
      factors induce TGF-beta expression in the kidney, one very interesting aspect is
      the link between the renin-angiotensin-aldosterone (Aldo) system (RAAS) and TGF
      beta. Angiotensin II (ANG II) stimulates TGF-beta expression in the kidney by
      various mechanisms and upregulates receptors for TGF-beta. ANG II can directly
      phosphorylate Smads without inducing TGF-beta. Recent data provide compelling
      evidence that other components of the RAAS including ANG III, renin, and Aldo
      also activate the TGF-beta system. As direct modulation of the TGF-beta system is
      not yet feasible in humans, angiotensin-converting enzyme (ACE) inhibitors and
      angiotensin type 1 (AT1)-receptor blockers are currently the most potential drugs
      to interfere with this ANG II-mediated TGF-beta expression. This review
      highlights some current aspects of the interaction between the RAAS and the TGF
      beta axis.

PMID- 16985516
TI  - Refractory hyponatremia.

PMID- 16985517
TI  - Do dialysate conductivity measurements provide conductivity clearance or ionic
      dialysance?
AB  - Dialysate conductivity measurements allow on-line estimation of urea clearance
      during hemodialysis session. Conductivity measurements provide a value of
      'conductivity clearance' for some authors, but a value of 'ionic dialysance' for
      others. This paper aims at explaining which term should be the more appropriate.
      Clearance is a parameter defined for measuring the power of a mechanism, which
      aims at 'clearing' a solution by depurating some solutes. In hemodialysis,
      clearance measures the efficacy of patient's depuration. In contrast, dialysance
      measures the capability of transferring solutes between blood and dialysate. The
      conventional definition of dialysance, requiring the absence of convective
      transfer, should be generalized to the case of the usual presence of
      ultrafiltration during the hemodialysis session. For a solute (as urea) absent
      from the dialysate delivered to the dialyzer inlet, the clearance is equal to its
      dialysance. In order to avoid a dramatic fall in ionic concentrations during
      hemodialysis treatment, the clearance of ions is reduced by adding these ions in
      the dialysate and becomes lower than their dialysance. Conductivity measurements
      provide a value of electrolytes dialysance. Thus the term of 'ionic dialysance'
      is more appropriate than the term of 'conductivity clearance'. Nevertheless ionic
      dialysance represents a good estimation of urea clearance.

PMID- 16985518
TI  - Atherosclerotic renal artery stenosis and reconstruction.
AB  - Renal artery stenosis is common especially in patients with generalized
      atherosclerosis. It is frequently associated with difficult-to-treat hypertension
      and with renal failure. There is an ongoing debate about the appropriate
      screening and treatment of atherosclerotic renal artery stenosis. Advances in
      imaging and interventional devices offer new opportunities, however, clinicians
      still have to decide individually in every patient to treat or not to treat
      stenosis with revascularization. This review evaluates the current literature in
      order to help the physician to find the right decision in this challenging
      clinical issue.

PMID- 16985519
TI  - Psychosocial effects on caregivers for children on chronic peritoneal dialysis.
AB  - The study was designed to explore the psychosocial effects on caretakers of
      children in Taiwan on chronic peritoneal dialysis (CPD). This is a case-control
      study, performed with subjects drawn from eight medical centers. The study group
      consisted of caretakers of 32 children with renal failure being treated with CPD.
      For comparison, a control group of caretakers of 64 healthy children as well as
      the regional Taiwanese studies were used. Two instruments were used to explore
      the presence of probable depression and quality of life (QOL) of the caretakers:
      the Taiwanese Depression Questionnaire, and the World Health Organization QOL
      BRIEF-Taiwan Version. In the study group, only 25% of caregivers had full-time
      jobs, and 66% of families had an annual income of less than US dollar 15,000. Of
      the 32 families in the study group, 16% had only a single parent. The prevalence
      of probable depression was significantly more common in the study group compared
      with control and referent group (28% vs 5% and 9.44%; P = 0.001). QOL scores in
      four domains were also significantly lower in the study group. In conclusion,
      even with the advances of peritoneal dialysis techniques, caring for children on
      CPD in Taiwan has significant adverse psychosocial effects on the primary
      caregivers. Attention should be paid to the psycho-social status of the
      caregivers.

PMID- 16985520
TI  - Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose
      tissue and ameliorates adipocytokine dysregulation.
AB  - Dysregulated production of adipocytokines may be involved in the development of
      atherosclerotic cardiovascular disease in metabolic syndrome and chronic kidney
      disease (CKD) associated with metabolic syndrome. The aim of this study was to
      determine the effects of treatment with angiotensin II (Ang II) type-1 receptor
      blocker (ARB) on the regulation of adipocytokines. Olmesartan, an ARB,
      significantly blunted the age- and body weight-associated falls in plasma
      adiponectin both in genetically and diet-induced obese mice, without affecting
      body weight, but had no effect on plasma adiponectin levels in lean mice.
      Olmesartan also ameliorated dysregulation of adipocytokines in obesity, such as
      tumor necrosis factor-alpha, plasminogen activator inhibitor-1, monocyte
      chemotactic protein-1, and serum amyloid A3. Olmesartan significantly reduced
      reactive oxygen species originating from accumulated fat and attenuated the
      expression of nicotinamide adenine dinucleotide phospho hydrogenase oxidase
      subunits in adipose tissue. In cultured adipocytes, olmesartan acted as an
      antioxidant and improved adipocytokine dysregulation. Our results indicate that
      blockade of Ang II receptor ameliorates adipocytokine dysregulation and that such
      action is mediated, at least in part, by targeting oxidative stress in obese
      adipose tissue. Ang II signaling and subsequent oxidative stress in adipose
      tissue may be potential targets for the prevention of atherosclerotic
      cardiovascular disease in metabolic syndrome and also in metabolic syndrome-based
      CKD.

PMID- 16985521
TI  - The pluripotent cytokine pleiotrophin is induced by wounding in human mesangial
      cells.
AB  - Mesangial re-modeling and mesangial cell (MC) migration are features of several
      glomerular diseases including mesangiocapillary glomerulonephritis. In vitro
      investigations have recently identified ADAM-15, a multidomain adamalysin, as
      central to the migration of MC. The current study used array technology to
      investigate the expression of other genes in migrating cells and identified
      pleiotrophin (PTN), platelet-derived growth factor alpha polypeptide chain,
      colony stimulating factor, and four members of the tumor necrosis factor-alpha
      superfamily as major genes that were upregulated. Transcriptional induction of
      PTN was confirmed by reverse transcription-polymerase chain reaction and Northern
      blotting and induction of the protein by Western blotting and immunohistochemical
      localization. PTN was observed associated with mesangial 'hillocks' in confluent
      MC cultures. In contrast, in models of migration, migrating cells had the highest
      expression of cell-associated PTN. PTN protein was less evident, however, in the
      conditioned medium of MCs. Treatment of MC with heparanase removed PTN from the
      cells suggesting that its localization was owing to an association with heparan
      sulfates on the cell surface or in the extracellular matrix. This is the first
      description of the expression of PTN by human MCs and the data suggest that it is
      rapidly induced in cells that are triggered to migrate. The result of this
      induction is currently under investigation.

PMID- 16985522
TI  - Frequency of metamerism in natural scenes.
AB  - Estimates of the frequency of metameric surfaces, which appear the same to the
      eye under one illuminant but different under another, were obtained from 50
      hyperspectral images of natural scenes. The degree of metamerism was specified
      with respect to a color-difference measure after allowing for full chromatic
      adaptation. The relative frequency of metameric pairs of surfaces, expressed as a
      proportion of all pairs of surfaces in a scene, was very low. Depending on the
      criterion degree of metamerism, it ranged from about 10(-6) to 10(-4) for the
      largest illuminant change tested, which was from a daylight of correlated color
      temperature 25,000 K to one of 4000 K. But, given pairs of surfaces that were
      indistinguishable under one of these illuminants, the conditional relative
      frequency of metamerism was much higher, from about 10(-2) to 10(-1),
      sufficiently large to affect visual inferences about material identity.

PMID- 16985523
TI  - Nonmydriatic fluorescence-based quantitative imaging of human macular pigment
      distributions.
AB  - We have developed a CCD-camera-based nonmydriatic instrument that detects
      fluorescence from retinal lipofuscin chromophores ("autofluorescence") as a means
      to indirectly quantify and spatially image the distribution of macular pigment
      (MP). The lipofuscin fluorescence intensity is reduced at all retinal locations
      containing MP, since MP has a competing absorption in the blue-green wavelength
      region. Projecting a large diameter, 488 nm excitation spot onto the retina,
      centered on the fovea, but extending into the macular periphery, and comparing
      lipofuscin fluorescence intensities outside and inside the foveal area, it is
      possible to spatially map out the distribution of MP. Spectrally selective
      detection of the lipofuscin fluorescence reveals an important wavelength
      dependence of the obtainable image contrast and deduced MP optical density
      levels, showing that it is important to block out interfering fluorescence
      contributions in the detection setup originating from ocular media such as the
      lens. Measuring 70 healthy human volunteer subjects with no ocular pathologies,
      we find widely varying spatial extent of MP, distinctly differing distribution
      patterns of MP, and strongly differing absolute MP levels among individuals. Our
      population study suggests that MP imaging based on lipofuscin fluorescence is
      useful as a relatively simple, objective, and quantitative noninvasive optical
      technique suitable to rapidly screen MP levels and distributions in healthy
      humans with undilated pupils.

PMID- 16985524
TI  - Reconstruction method with data from a multiple-site continuous-wave source for
      three-dimensional optical tomography.
AB  - A method is presented for reconstruction of the optical absorption coefficient
      from transmission near-infrared data with a cw source. As it is distinct from
      other available schemes such as optimization or Newton's iterative method, this
      method resolves the inverse problem by solving a boundary value problem for a
      Volterra-type integral-differential equation. It is demonstrated in numerical
      studies that this technique has a better than average stability with respect to
      the discrepancy between the initial guess and the actual unknown absorption
      coefficient. The method is particularly useful for reconstruction from a large
      data set obtained from a CCD camera. Several numerical reconstruction examples
      are presented.

PMID- 16985525
TI  - Radiometric order preserving method to display wide-dynamic images for imagery
      photointerpretation.
AB  - Wide-dynamic numerical images are increasingly frequent in professional
      environments, military photointerpretation, and x-ray or magnetic resonance
      medical imagery. However, a dynamic compression process is necessary to exploit
      such images without incessant image manipulation. A wealth of efficient methods
      has been developed to tackle this problem on aesthetic grounds. We argue that
      professional imagery interpretation needs preservation of the original
      radiometric order. We develop a measure of image efficiency use of the 8-bit
      radiometric channel and find that it correlates nicely with subjective appraisal.
      The image underscores a radiometric order-preserving process to reach a standard
      radiometric efficiency. Lost information is then reintroduced by addition of an
      edge image devoid of artifacts, with an automatic weighting ensuring a natural
      looking image.

PMID- 16985526
TI  - Using Fisher information to approximate ideal-observer performance on detection
      tasks for lumpy-background images.
AB  - When building an imaging system for detection tasks in medical imaging, we need
      to evaluate how well the system performs before we can optimize it. One way to do
      the evaluation is to calculate the performance of the Bayesian ideal observer.
      The ideal-observer performance is often computationally expensive, and it is very
      useful to have an approximation to it. We use a parameterized probability density
      function to represent the corresponding densities of data under the signal-absent
      and the signal-present hypotheses. We develop approximations to the ideal
      observer detectability as a function of signal parameters involving the Fisher
      information matrix, which is normally used in parameter estimation problems. The
      accuracy of the approximation is illustrated in analytical examples and lumpy
      background simulations. We are able to predict the slope of the detectability as
      a function of the signal parameter. This capability suggests that the Fisher
      information matrix itself evaluated at the null parameter value can be used as
      the figure of merit in imaging system evaluation. We are also able to provide a
      theoretical foundation for the connection between detection tasks and estimation
      tasks.

PMID- 16985527
TI  - Reflectance and transmittance model for recto-verso halftone prints.
AB  - We propose a spectral prediction model for predicting the reflectance and
      transmittance of recto-verso halftone prints. A recto-verso halftone print is
      modeled as a diffusing substrate surrounded by two inked interfaces in contact
      with air (or with another medium). The interaction of light with the print
      comprises three components: (a) the attenuation of the incident light penetrating
      the print across the inked interface, (b) the internal reflectance and internal
      transmittance that accounts for the substrate's intrinsic reflectance and
      transmittance and for the multiple Fresnel internal reflections at the inked
      interfaces, and (c) the attenuation of light exiting the print across the inked
      interfaces. Both the classical Williams-Clapper and Clapper-Yule spectral
      prediction models are special cases of the proposed recto-verso reflectance and
      transmittance model. We also extend the Kubelka-Munk model to predict the
      reflectance and transmittance of recto-verso halftone prints. The extended
      Kubelka-Munk model is compatible with the proposed recto-verso reflectance and
      transmittance model. In the case of a homogeneous substrate, the recto-verso
      model's internal reflectance and transmittance can be expressed as a function
      Kubelka-Munk's scattering and absorption parameters, or the Kubelka-Munk's
      scattering and absorption parameters can be inferred from the recto-verso model's
      internal reflectance and transmittance, deduced from spectral measurements. The
      proposed model offers new perspectives both for spectral transmission and
      reflection predictions and for characterizing the properties of printed diffuse
      substrates.

PMID- 16985528
TI  - Inverse scattering for rotationally scanned optical coherence tomography.
AB  - Optical coherence tomography of luminal structures, such as for intravascular or
      gastrointestinal imaging, is performed by using a fiber-optic catheter as a beam
      delivery probe. The interrogating beam is scanned angularly by rotating the fiber
      around a fixed central axis. Because the beam is focused only at a fixed distance
      from the center of the fiber, only scatterers near this distance are resolved. We
      present a solution of the inverse scattering problem that provides an estimate of
      the susceptibility of the sample for an angularly scanned Gaussian beam focused
      at a fixed distance from the origin. This solution provides quantitatively
      meaningful reconstructions while also extending the volume of the sample that is
      resolvable by the instrument.

PMID- 16985529
TI  - Singular-value decomposition for through-focus imaging systems.
AB  - Singular-value decomposition (SVD) of a linear imaging system gives information
      on the null and measurement components of object and image and provides a method
      for object reconstruction from image data. We apply SVD to through-focus imaging
      systems that produce several two-dimensional images of a three-dimensional
      object. Analytical expressions for the singular functions are derived in the
      geometrical approximation for a telecentric, laterally shift-invariant system
      linear in intensity. The modes are evaluated numerically, and their accuracy
      confirmed. Similarly, the modes are derived and evaluated for a continuous image
      representing the limit of a large number of image planes.

PMID- 16985530
TI  - Image denoising using the ridgelet bi-frame.
AB  - We are concerned with the performance evaluation of the ridgelet bi-frame for
      image denoising application. The ridgelet bi-frame is a new (as far as we know)
      bi-frame system that can efficiently deal with straight singularities in two
      dimensions. We show that, for images dominated by straight edges, the ridgelet bi
      frame can obtain much better restoration results than wavelet systems. We also
      investigate the statistical properties of the ridgelet bi-frame coefficients of
      these images. Results indicate that the marginal distribution of ridgelet bi
      frame coefficients has higher kurtosis than that of wavelet coefficients of the
      same images. We describe a simple method through which statistical denoising
      algorithms previously developed in the wavelet domain can be conveniently
      introduced into the ridgelet bi-frame domain. In addition, we use the ridgelet bi
      frame to construct another new bi-frame system referred to as the curvelet bi
      frame, which can be viewed as a generalized version of the curvelet. Experiment
      results show that the simple hard-threshold procedure in the curvelet bi-frame
      domain produces restoration results comparable with those due to the state-of-the
      art denoising methods.

PMID- 16985532
TI  - Retrieving two-dimensional information of the subwavelength variation from far
      field irradiance.
AB  - An eigenvalue-problem approach of blind deconvolution is developed to retrieve
      the information of two-dimensional subwavelength variation from far-field
      irradiance with an embedded-aperture configuration with three detectors. A
      reference signal has been implemented to determine the scaling issue, and hence
      it allows the exact order of magnitude of the retrieved signals to be estimated
      correctly. It is shown that the subwavelength variations of a two-dimensional
      aperture can be identified with a precision of better than a 1% error ratio.

PMID- 16985531
TI  - Object-of-interest image segmentation based on human attention and semantic
      region clustering.
AB  - We propose a novel object-of-interest (OOI) segmentation algorithm for various
      images that is based on human attention and semantic region clustering. As object
      based image segmentation is beyond current computer vision techniques, the
      proposed method segments an image into regions, which are then merged as a
      semantic object. At the same time, an attention window (AW) is created based on
      the saliency map and saliency points from an image. Within the AW, a support
      vector machine is used to select the salient regions, which are then clustered
      into the OOI using the proposed region merging. Unlike other algorithms, the
      proposed method allows multiple OOIs to be segmented according to the saliency
      map.

PMID- 16985533
TI  - Reduced-complexity representation of the coherent point-spread function in the
      presence of aberrations and arbitrarily large defocus.
AB  - We introduce a method to analyze the diffraction integral for evaluating the
      point-spread function. Our method is based on the use of higher-order Airy
      functions along with Zernike and Taylor expansions. Our approach is applicable
      when we are considering a finite, arbitrary number of aberrations and arbitrarily
      large defocus simultaneously. We present an upper bound for the complexity and
      the convergence rate of this method. We also compare the cost and accuracy of
      this method with those of traditional ones and show the efficiency of our method
      through these comparisons. In particular, we rigorously show that this method is
      constructed in a way that the complexity of the analysis (i.e., the number of
      terms needed for expressing the light disturbance) does not increase as either
      defocus or resolution of interest increases. This has applications in several
      fields such as biological microscopy, lithography, and multidomain optimization
      in optical systems.

PMID- 16985534
TI  - Optical system design for orthosymplectic transformations in phase space.
AB  - On the basis of a matrix formalism, we analyze the paraxial optical systems
      composed by generalized lenses and fixed free-space intervals, suitable for
      orthosymplectic transformations in phase space. Flexible configurations to
      perform the attractive operations for optical information processing such as
      image rotation, separable fractional Fourier transformation, and twisting for
      different parameters are proposed.

PMID- 16985535
TI  - Modal method in deep metal-dielectric gratings: the decisive role of hidden
      modes.
AB  - The modal method is well adapted for the modeling of deep-groove, high-contrast
      gratings of short period, possibly involving metal parts. Yet problems remain in
      the case of the TM polarization in the presence of metal parts in the
      corrugations: whereas most of the diffraction features are explained by the
      interplay of an astonishingly small number of true propagating and low-order
      evanescent modes, the exact solution of the diffraction problem requires the
      contribution of two types of evanescent modes that are usually overlooked. We
      investigate the nature and the role of these modes and show that metal gratings
      can be treated exactly by the modal method.

PMID- 16985536
TI  - Second-harmonic diffraction from holographic volume grating.
AB  - The full polarization property of holographic volume-grating enhanced second
      harmonic diffraction (SHD) is investigated theoretically. The nonlinear
      coefficient is derived from a simple atomic model of the material. By using a
      simple volume-grating model, the SHD fields and Mueller matrices are first
      derived. The SHD phase-mismatching effect for a thick sample is analytically
      investigated. This theory is justified by fitting with published experimental SHD
      data of thin-film samples. The SHD of an existing polymethyl methacrylate (PMMA)
      holographic 2-mm-thick volume-grating sample is investigated. This sample has two
      strong coupling linear diffraction peaks and five SHD peaks. The splitting of SHD
      peaks is due to the phase-mismatching effect. The detector sensitivity and laser
      power needed to measure these peak signals are quantitatively estimated.

PMID- 16985537
TI  - Young's experiment with electromagnetic spatial coherence wavelets.
AB  - We discuss Young's experiment with electromagnetic random fields at arbitrary
      states of coherence and polarization within the framework of the electric spatial
      coherence wavelets. The use of this approach for the electromagnetic spatial
      coherence theory allows us to envisage the existence of polarization domains
      inside the observation plane. We show that it is possible to locally control
      those polarization domains by means of the correlation properties of the
      electromagnetic wave. To show the validity of this alternative approach, we
      derive by means of numerical modeling the classical Fresnel-Arago interference
      laws.

PMID- 16985538
TI  - Quasi-stationary plane-wave optical pulses and the van Cittert-Zernike theorem in
      time.
AB  - We study the properties of quasi-stationary, partially coherent, plane-wave
      optical pulses in the space-time and space-frequency domains. A generalized van
      Cittert-Zernike theorem in time is derived to describe the propagation of the
      coherence function of quasi-stationary pulses. The theory is applied to
      rectangular pulses chopped from a stationary light source, and the evolution
      characteristics of such pulse trains with different states of coherence are
      discussed and illustrated with numerical examples.

PMID- 16985539
TI  - Electromagnetic wave scattering from moving surfaces with high-amplitude
      corrugated pattern.
AB  - This paper deals with the problem of electromagnetic wave scattering from rough
      surfaces. By means of a generalized Floquet modal representation an analytic
      solution can be found that is valid for any Fourier-expandable surface pattern,
      with no limitation on the corrugation amplitude. By means of the special
      relativistic frame-hopping method, the motionless solution is generalized to the
      case of uniform translational relative motion between the surface and the
      observer. Plane-wave simplification techniques are employed to minimize the
      algebraic complexity of the field covariance transformations. A detailed signal
      analysis of the electromagnetic scattered field is performed in both the
      frequency and the time domains.

PMID- 16985540
TI  - Tomographic method for measurement of the gradient refractive index of the
      crystalline lens. II. The rotationally symmetrical lens.
AB  - In the first part of this paper we presented a tomographic method to reconstruct
      the refractive index profile of spherically symmetrical lenses. Here we perform
      the generalization to lenses that are rotationally symmetrical around the optical
      axis, as is the ideal human lens. Analysis of the accuracy and versatility of
      this method is carried out by performing numerical simulations in which different
      magnitudes of experimental errors and two extreme case scenarios for the likely
      shape of the refractive index distribution of the human lens are considered.
      Finally, experimental results for a porcine lens are shown. Conceptually simple
      and computationally swift, this method could prove to be a valuable tool for the
      accurate retrieval of the gradient index of a broad spectrum of rotationally
      symmetrical crystalline lenses.

PMID- 16985541
TI  - Inverse scattering from phaseless measurements of the total field on open lines.
AB  - A new solution approach to inverse scattering from aspect-limited phaseless
      measurements of the total field is introduced and discussed. In analogy with the
      case of measurements on closed curves [J. Opt. Soc. Am. A21, 622 (2004)], the
      procedure splits the problem into two different steps. In the first step,
      amplitude and phase of the scattered field are estimated from only amplitude
      information of the total field. By properly extending the concept of reduced
      radiated field to the case of scattered fields (as a function of both
      illumination and measurement variables) and taking advantage of the properties of
      the square amplitude distribution of the total field, criteria are given for an
      optimal choice of the measurement setup and a successful retrieval. Then the
      complex permittivity profile is reconstructed in the second step, starting from
      the scattered fields estimated in the previous step. Numerical examples are
      provided to assess the effectiveness of the whole chain in the presence of noise
      corrupted data and the relevance of the representation introduced for the
      scattered fields.

PMID- 16985542
TI  - Convergence of the discrete dipole approximation. I. Theoretical analysis.
AB  - We perform a rigorous theoretical convergence analysis of the discrete dipole
      approximation (DDA). We prove that errors in any measured quantity are bounded by
      a sum of a linear term and a quadratic term in the size of a dipole d when the
      latter is in the range of DDA applicability. Moreover, the linear term is
      significantly smaller for cubically than for noncubically shaped scatterers.
      Therefore, for small d, errors for cubically shaped particles are much smaller
      than for noncubically shaped ones. The relative importance of the linear term
      decreases with increasing size; hence convergence of DDA for large enough
      scatterers is quadratic in the common range of d. Extensive numerical simulations
      are carried out for a wide range of d. Finally, we discuss a number of new
      developments in DDA and their consequences for convergence.

PMID- 16985543
TI  - Convergence of the discrete dipole approximation. II. An extrapolation technique
      to increase the accuracy.
AB  - We propose an extrapolation technique that allows accuracy improvement of
      discrete dipole approximation computations. The performance of this technique was
      studied empirically on the basis of extensive simulations for five test cases
      using many different discretizations. The quality of the extrapolation improves
      with refining discretization, reaching extraordinary performance especially for
      cubically shaped particles. A 2-order-of-magnitude decrease of error is
      demonstrated. We also propose estimates of the extrapolation error, which are
      proven to be reliable. Finally, we propose a simple method to directly separate
      shape and discretization errors and illustrate this for one test case.

PMID- 16985544
TI  - Correctability limitations imposed by plane-wave scintillation in multiconjugate
      adaptive optics.
AB  - Plane-wave scintillation is shown to impose multiconjugate adaptive optics (MCAO)
      correctability limitations that are independent of wavefront sensing and
      reconstruction. Residual phase and log-amplitude variances induced by
      scintillation in weak turbulence are derived using linear (diffraction-based)
      diffractive MCAO spatial filters or (diffraction-ignorant) geometric MCAO
      proportional gains as open-loop control parameters. In the case of Kolmogorov
      turbulence, expressions involving the Rytov variance and/or weighted C(2)(n)
      integrals apply. Differences in performance between diffractive MCAO and
      geometric MCAO resemble chromatic errors. Optimal corrections based on least
      squares imply irreducible performance limits that are validated by wave-optic
      simulations.

PMID- 16985545
TI  - Adaptive wavefront control with asynchronous stochastic parallel gradient descent
      clusters.
AB  - A scalable adaptive optics (AO) control system architecture composed of
      asynchronous control clusters based on the stochastic parallel gradient descent
      (SPGD) optimization technique is discussed. It is shown that subdivision of the
      control channels into asynchronous SPGD clusters improves the AO system
      performance by better utilizing individual and/or group characteristics of
      adaptive system components. Results of numerical simulations are presented for
      two different adaptive receiver systems based on asynchronous SPGD clusters-one
      with a single deformable mirror with Zernike response functions and a second with
      tip-tilt and segmented wavefront correctors. We also discuss adaptive wavefront
      control based on asynchronous parallel optimization of several local performance
      metrics-a control architecture referred to as distributed adaptive optics (DAO).
      Analysis of the DAO system architecture demonstrated the potential for
      significant increase of the adaptation process convergence rate that occurs due
      to partial decoupling of the system control clusters optimizing individual
      performance metrics.

PMID- 16985546
TI  - Partially coherent flattened Gaussian beam and its paraxial propagation
      properties.
AB  - A simple model called partially coherent flattened Gaussian beam (FGB) is
      proposed to describe a partially coherent beam with a flat-topped spatial
      profile. An explicit and analytical formula is derived for the cross-spectral
      density of a partially coherent FGB propagating through a paraxial ABCD optical
      system. The propagation factor and propagation properties of a partially coherent
      FGB in free space are studied in detail and found to be closely related to its
      coherence and beam order.

PMID- 16985547
TI  - Quantifications of error propagation in slope-based wavefront estimations.
AB  - We discuss error propagation in the slope-based and the difference-based
      wavefront estimations. The error propagation coefficient can be expressed as a
      function of the eigenvalues of the wavefront-estimation-related matrices, and we
      establish such functions for each of the basic geometries with the serial
      numbering scheme with which a square sampling grid array is sequentially indexed
      row by row. We first show that for the wavefront estimation with the wavefront
      piston value determined, the odd-number grid sizes yield better error propagators
      than the even-number grid sizes for all geometries. We further show that for both
      slope-based and difference-based wavefront estimations, the Southwell geometry
      offers the best error propagators with the minimum-norm least-squares solutions.
      Noll's theoretical result, which was extensively used as a reference in the
      previous literature for error propagation estimates, corresponds to the Southwell
      geometry with an odd-number grid size. Typically the Fried geometry is not
      preferred in slope-based optical testing because it either allows subsize
      wavefront estimations within the testing domain or yields a two-rank deficient
      estimations matrix, which usually suffers from high error propagation and the
      waffle mode problem. The Southwell geometry, with an odd-number grid size if a
      zero point is assigned for the wavefront, is usually recommended in optical
      testing because it provides the lowest-error propagation for both slope-based and
      difference-based wavefront estimations.

PMID- 16985548
TI  - Determination of film thickness and refractive index in one measurement of phase
      modulated ellipsometry.
AB  - Ellipsometry is often used to determine the refractive index and/or the thickness
      of a polymer layer on a substrate. However, simultaneous determination of these
      parameters from a single-wavelength single-angle measurement is not always
      possible. The present study determines the sensitivity of the method to errors of
      measurement for the case of phase modulated ellipsometry and identifies
      conditions for decoupling film thickness and refractive index. For a specific
      range of film thickness, both the thickness and the refractive index can be
      determined from a single measurement with high precision. This optimal range of
      the film thickness is determined for organic thin films, and the analysis is
      tested on hydrogel-like polymer films in air and in water.

PMID- 16985549
TI  - Sidelobe suppression design of etched diffraction grating demultiplexers using
      optimized air trenches in front of each output waveguide.
AB  - An etched diffraction grating (EDG) demultiplexer with high sidelobe suppression
      is designed. Sidelobes resulting from two adjacent wavelengths are suppressed by
      etching two optimized rectangular air trenches in front of each output waveguide
      that can induce large resonance loss in the adjacent wavelength but have little
      influence on the operational wavelength. The designed EDG demultiplexer can
      suppress crosstalk to less than 50 dB in theory.

PMID- 16985550
TI  - Analytical method for the identification of a thin-strip defect in a planar
      waveguide.
AB  - Nondestructive reconstruction of the location and width of a thin-strip defect in
      a strongly confined planar waveguide is considered. Explicit reconstruction
      formulas are given for a quick reconstruction of a thin-strip defect whose width
      is small by measuring the scattered fields at the two end faces of the planar
      waveguide for two frequencies. Numerical results are given, and the analytical
      reconstruction method is shown to be reliable regardless of the location of the
      defect.

PMID- 16985551
TI  - A posteriori quasi-sectioning of the three-dimensional reconstructions of
      scanning holographic microscopy.
AB  - A method to obtain the axial locations of objects reconstructed by scanning
      holographic microscopy with submicrometer accuracy is presented and demonstrated.
      The method combines the holographic advantage of capturing three-dimensional (3D)
      information in a single two-dimensional scan, with the possibility of optically
      sectioning the 3D holographic reconstruction a posteriori. The method is
      demonstrated experimentally for pointlike features (fluorescent beads), and the
      limitation of the method for features of arbitrary size and shape is discussed.

PMID- 16985552
TI  - Separate and simultaneous investigation of absorption gratings and refractive
      index gratings by beam-coupling analysis: comment.
AB  - We correct a fundamental error occurring in the paper by F. Kahmann [J. Opt. Soc.
      Am. A10, 1562 (1993)] leading to a different value for the parameter varphi(p,0),
      i.e., the initial phase shift for the complex grating.

PMID- 16985553
TI  - Selected Risk Factors for Cancer among Koreans Residing in California.
AB  - Preliminary analysis of data (N=2,441) drawn from an ongoing population-based
      study of people of Korean descent who reside in California revealed the presence
      of selected cancer risk factors, especially tobacco use and lack of vigorous
      exercise. Men and women differed in cancer risks, with men being more likely than
      women to be smokers, less likely to exercise, more likely to be obese, and more
      likely to consume alcohol. Although relationships between demographic
      characteristics and cancer risks differed in strength by gender, patterns of
      correlation were similar among men and women. Future studies should explore the
      relationship between lifestyle and health risk interactions by gender in greater
      detail.

PMID- 16985554
TI  - Surveillance strategies for renal cell carcinoma patients following nephrectomy.
AB  - Renal cell carcinoma (RCC) is the most lethal of urologic malignancies,
      accounting for an estimated 36,000 new cases of carcinoma and 12,000 deaths in
      2005. Nephrectomy is the usual treatment; however, after nephrectomy, RCC recurs
      in 20% to 40% of patients with clinically localized disease. A consensus
      surveillance protocol does not exist for follow-up of RCC after nephrectomy. In
      this article, available protocols are reviewed with a goal of developing an
      evidence-based system including the prognostic factors for recurrent disease,
      chronology and sites of recurrence, available treatment options if recurrent
      disease is found, and modalities of diagnostic testing available to urologists.
      New surveillance recommendations are presented based on prognostic factors as
      well as the University of California, Los Angeles Integrated Staging System for
      RCC.

PMID- 16985555
TI  - Chemopreventive trials in urologic cancer.
AB  - Cancer prevention uses natural, synthetic, or biological chemical agents to
      reverse, suppress, or prevent carcinogenic progression. Chemoprevention trials
      are based on the hypothesis that interruption of the biological process involved
      in carcinogenesis will inhibit this process and, in turn, reduce cancer
      incidence. Bladder cancer chemoprevention trials demonstrate conflicting
      findings. Dietary fat, soy protein, garlic, and selenium have been reported to
      possess anticancer properties in the bladder, but they still remain largely
      unstudied in vivo. Regarding prostate cancer, vitamin D deficiency was reported
      to increase risk for the disease, and sunlight exposure is inversely proportional
      to prostate cancer mortality. The Prostate Cancer Prevention Trial reported a
      24.4% prostate cancer incidence with placebo, compared with 18.4% with
      finasteride, and a reduction of 24.8% over 7 years. Dutasteride, a dual inhibitor
      of type 1 and type 2 5alpha-reductase, is the subject of the Reduction by
      Dutasteride of Prostate Cancer Events trial. Results are awaited from that study.

PMID- 16985556
TI  - Medical therapy for benign prostatic hyperplasia: new terminology, new concepts,
      better choices.
AB  - This article discusses 3 areas of medical therapy for benign prostatic
      hyperplasia (BPH) that are undergoing extensive research and evaluation: 1) the
      use of muscarinic receptor antagonists to treat lower urinary tract symptoms
      (LUTS) in men with BPH; 2) the definition of an "enlarged prostate"; and 3)
      sexual function and LUTS. Fears of worsening obstructive symptoms or causing
      acute urinary retention often keep practitioners from prescribing muscarinic
      receptor antagonists to men who might have concomitant bladder outlet
      obstruction; a multicenter, multinational, double-blind study showed that
      tolterodine is safe for men with low postvoid residual volumes. Most urologists
      accept that a prostate volume of more than 40 mL is consistent with an enlarged
      prostate; there is more debate regarding prostate volumes of 30 to 40 mL.
      Recently presented data suggest that combination medical therapy might be
      effective for men having prostates with volumes of more than 25 mL. The
      association between voiding and sexual function has been increasingly recognized
      and investigated, and there seem to be common pathophysiologic mechanisms
      governing both conditions. Targeted treatment algorithms addressing both
      conditions seem warranted.

PMID- 16985558
TI  - Changing paradigms for chronic pelvic pain: a report from the chronic pelvic
      pain/chronic prostatitis scientific workshop, october 19-21, 2005, Baltimore, MD.

PMID- 16985557
TI  - Updates in Pediatric Urology: Highlights of the American Academy of Pediatrics
      Section on Urology Annual Meeting, October 8-10, 2005, Washington, DC.

PMID- 16985560
TI  - The predictive capability of prostate-specific antigen kinetics.

PMID- 16985561
TI  - Freeze that Sperm.

PMID- 16985559
TI  - Spontaneous retroperitoneal hemorrhage caused by segmental arterial mediolysis.
AB  - Spontaneous retroperitoneal hemorrhage is a rare clinical entity; signs and
      symptoms include pain, hematuria, and shock. Spontaneous retroperitoneal
      hemorrhage can be caused by tumors, such as renal cell carcinoma and
      angiomyolipoma; polyarteritis nodosa; and nephritis. The least common cause is
      segmental arterial mediolysis. Although computed tomography is used for the
      diagnosis of spontaneous retroperitoneal hemorrhage, it can miss segmental
      arterial mediolysis as the cause of the hemorrhage. The diagnosis of segmental
      arterial mediolysis as a cause of spontaneous retroperitoneal hemorrhage requires
      angiography, with pathologic confirmation for a definitive diagnosis.

PMID- 16985562
TI  - Lower urinary tract symptoms, erectile dysfunction, and hypogonadism.

PMID- 16985563
TI  - Diabetes mellitus and kidney stone formation.

PMID- 16985564
TI  - Anemia in men with advanced prostate cancer: incidence, etiology, and treatment.
AB  - Anemia associated with advanced prostate cancer is a common occurrence. This
      article reviews the incidence and examines the various causes of this condition,
      including androgen deprivation, nutritional decline, bone marrow infiltration,
      treatment-related toxicity, and the chronic inflammatory state. Treatment of
      anemia in men with advanced prostate cancer is also discussed. In patients with
      limited bone marrow reserve, blood transfusions may be the only effective
      treatment.

PMID- 16985565
TI  - Managing early ejaculation: what does the future hold?
AB  - Recent attention in the field of male sexual dysfunction has focused on erectile
      dysfunction. However, premature ejaculation (PE) is an extremely common condition
      that warrants clinical study and exploration of pharmacologic treatments. Until
      recently, PE was thought to be a behavioral problem for which the best remedy was
      a learned control technique. However, some drugs currently on the market,
      including sildenafil and the selective serotonin reuptake inhibitors, appear to
      have efficacy in the treatment of PE. More research is needed before FDA approval
      of such agents for this indication, but more and better options for men with PE
      are anticipated as attention to ejaculatory disorders grows and, hopefully, the
      associated stigma decreases.

PMID- 16985566
TI  - Prepubertal testis tumors.
AB  - Because prepubertal testis tumors are rare, their management has historically
      been based on experience with the more common adult testis tumors. However,
      recent studies highlighting the natural history of these tumors and their
      response to therapy have resulted in a modern management algorithm that optimizes
      testicular preservation and minimizes the morbidity of adjuvant therapies. Many
      prepubertal testis tumors are benign and can be managed with testis-sparing tumor
      excision. Localized malignant tumors (yolk sac tumors) may be managed with
      excision alone. Recurrent tumors and metastatic disease can almost always be
      treated successfully with platinum-based chemotherapy.

PMID- 16985567
TI  - New Findings in Prostate Cancer, Benign Prostatic Hyperplasia, and Sexual
      Dysfunction: Highlights from the XVIII Congress of the European Association of
      Urology, March 12-15, 2003, Madrid, Spain.

PMID- 16985568
TI  - Recognition and treatment of bladder outlet obstruction after sling surgery.
AB  - At the University of Pittsburgh School of Medicine, our experience with
      urethrolysis over the past several years offered a unique opportunity to assess
      outcomes after delayed time to urethrolysis. We observed a highly suggestive
      association between prolonged time to urethrolysis and a greater likelihood of
      persistent bladder dysfunction. If this observation is corroborated by other
      studies, it would be prudent to lower our threshold of clinical suspicion to
      detect bladder outlet obstruction. Videourodynamics testing can be invaluable for
      making the distinction between outlet obstruction versus de novo urge
      incontinence. Here, we briefly review the literature on urethrolysis and present
      the urethrolysis technique utilized at our institution. The article concludes
      with several challenging and controversial clinical judgment questions asked ofDr
      Leng by Dr Chancellor.

PMID- 16985569
TI  - 39-year-old man with voiding symptoms.

PMID- 16985571
TI  - Use of desmopressin in the elderly.

PMID- 16985570
TI  - Primary leiomyosarcoma of the inferior vena cava presenting as a renal mass.
AB  - Leiomyosarcoma of the inferior vena cava (IVC) is an extremely rare entity. We
      present the case of a 62-year-old woman who was found to have a large right upper
      quadrant mass upon examination by her primary care physician in evaluation for
      diffuse abdominal pain accompanied by anorexia and weight loss. A computed
      tomographic scan and magnetic resonance imaging demonstrated a 13-cm
      retroperitoneal lesion that appeared to stem from the right kidney and yielded a
      tumor thrombus up to the level of the hepatic venous confluence. The patient
      underwent a right radical nephrectomy and IVC thrombectomy for treatment of a
      presumed renal cell carcinoma. Instead, pathology revealed the tumor to be a
      leiomyosarcoma of the IVC. We document this unusual presentation of an extremely
      rare tumor entity.

PMID- 16985572
TI  - Tissue microarrays in prostate cancer research.

PMID- 16985573
TI  - The effects of phosphodiesterase-5 inhibitors in men with "normal" erectile
      function.

PMID- 16985574
TI  - Vasectomy and prostate cancer.

PMID- 16985575
TI  - Endothelin-a receptor antagonists and advanced prostate cancer.

PMID- 16985576
TI  - Incontinence after childbirth.

PMID- 16985577
TI  - Dynamic contrast-enhanced magnetic resonance imaging for the evaluation of
      hydronephrosis in children.

PMID- 16985578
TI  - Advances toward tissue engineering for the treatment of stress urinary
      incontinence.
AB  - Suburethral pubovaginal sling placement is a common surgical procedure for the
      treatment of stress urinary incontinence. A wide variety of graft materials is
      available, each associated with inherent desirable and undesirable
      characteristics and complications. In this article, we discuss the rationale for
      and application of small intestinal submucosa (SIS) in lower urinary tract tissue
      engineering, with emphasis on the use of SIS as a suitable and biologically
      compatible sling material. In addition, we discuss exciting research regarding
      the engineering of true functional sphincter reconstruction using this biologic
      scaffold and pre-seeded muscle cells.

PMID- 16985579
TI  - Beyond prostate-specific antigen: new serologic biomarkers for improved diagnosis
      and management of prostate cancer.
AB  - The use of total prostate-specific antigen (tPSA) measurement has dramatically
      improved the ability to detect prostate cancer at earlier stages. However, as the
      number of men presenting with advanced disease (and high tPSA levels) has
      decreased, and given the fact that tPSA is highly reflective of benign prostatic
      hyperplasia, the need has emerged for novel biomarkers specifically associated
      with prostate cancer in order to improve predictive models. Several new
      biomarkers have shown promise, and studies continue to investigate the role of
      these markers in the detection, staging, and prognosis of prostate cancer. As new
      useful biomarkers continue to emerge, guidelines for their employment, as well as
      coordination of further research studies, are needed; a systematic, phased,
      nomogram-based model is a rational way to manage these efforts.

PMID- 16985581
TI  - Advances in endourology: highlights from the 21st world congress on endourology
      and shockwave lithotripsy/19th basic research symposium, september 21-24, 2003,
      montreal, Canada.

PMID- 16985582
TI  - Updates in pediatric urology: highlights from the american academy of pediatrics
      section on urology annual meeting, october 31-november 3, 2003, new orleans, la.

PMID- 16985580
TI  - Examining the relationship between obesity and prostate cancer.
AB  - Affecting over 30% of the population, obesity is an epidemic in the United States
      and is associated with multiple chronic medical problems. Obesity is also
      associated with numerous hormonal changes, many of which have been implicated in
      prostate cancer development and progression. Although, on the whole, controversy
      exists over whether obesity increases the risk of prostate cancer, data strongly
      suggest that obesity is a significant risk factor for prostate cancer death. In
      this review, we discuss the epidemiologic data surrounding obesity and prostate
      cancer. We also discuss some of the sequelae of obesity and their relationships
      with prostate cancer, including alterations in insulin, the insulin-like growth
      factor axis, and leptin levels; insulin resistance; and diabetes. Although a
      complete overview of all the various dietary and lifestyle factors that are
      associated with obesity and prostate cancer risk is beyond the scope of this
      review, we discuss data concerning the relationship between a high-fat diet and
      prostate cancer.

PMID- 16985583
TI  - Rising prostate-specific antigen level after prostatectomy.

PMID- 16985584
TI  - Androgen replacement therapy and prostate cancer: is androgen replacement safe in
      high-risk patients?

PMID- 16985585
TI  - Estrogen for overactive bladder and patient perception of incontinence.

PMID- 16985586
TI  - Vitamin d for the management of prostate cancer.

PMID- 16985587
TI  - Finasteride and prostate cancer.

PMID- 16985588
TI  - Overview of biodegradable urethral stents.

PMID- 16985589
TI  - Expectant management in neonatal reflux.

PMID- 16985590
TI  - Imaging in the diagnosis and management of prostate cancer.
AB  - The current diagnosis and management of prostate cancer is largely based on the
      use of serum prostate-specific antigen (PSA) and pathologic risk factors such as
      Gleason score and clinical stage. The use of serum PSA in clinical practice has
      resulted in significant stage migration and, as such, imaging modalities
      historically utilized to stage prostate cancer are no longer able to reliably
      identify the small amounts of prostate cancer most often found at presentation.
      Molecular imaging techniques have focused on improving sensitivity and
      specificity for cancer detection through knowledge of specific attributes of
      disease biology. The evolution of imaging techniques has created a new role for
      imaging in the management of prostate cancer.

PMID- 16985591
TI  - Current treatment options for penile fractures.
AB  - The diagnosis of "penile fracture" describes the traumatic rupture of the tunica
      albuginea of an erect penis. Penile fractures typically occur when the engorged
      penile corpora are forced to buckle and literally "pop" under the pressure of a
      blunt sexual trauma. Patients typically describe immediate detumescence, severe
      pain, and swelling as a result of the injury. Prompt surgical exploration and
      corporal repair is the most efficacious therapy. Although a majority of cases can
      be diagnosed from the history and physical examination alone, radiographic
      studies, including retrograde urethrography and corporal cavernosography can aid
      in the diagnosis of unusual cases.

PMID- 16985592
TI  - Lower urinary tract symptoms, benign prostatic hyperplasia, erectile dysfunction,
      and phosphodiesterase-5 inhibitors.
AB  - Many patients who present to their healthcare provider with lower urinary tract
      symptoms (LUTS) due to benign prostatic hyperplasia (BPH) will also have erectile
      dysfunction (ED), and vice versa. Although alpha-adrenergic receptor blockers and
      5-alpha-reductase inhibitors are highly effective in treating BPH-associated
      LUTS, these agents have sexual adverse effects that cause many men to discontinue
      therapy. The discovery of nitric oxide as a major factor in the mechanism of
      erection has led to the development of new drugs for ED, including the
      phosphodiesterase (PDE) inhibitors. Preliminary data support the theory that
      inhibition of PDE isoenzymes in the prostate may improve LUTS due to BPH through
      relaxation of prostatic smooth muscle. Further studies of PDE inhibitors in men
      with ED and BPH-associated LUTS are indicated.

PMID- 16985593
TI  - Best of the 2004 AUA Annual Meeting: Highlights from the 2004 Annual Meeting of
      the American Urological Association, May 8-13, 2004, San Francisco, CA.

PMID- 16985594
TI  - 54-year-old woman with clitoromegaly.

PMID- 16985595
TI  - Treatment of mixed incontinence.

PMID- 16985596
TI  - Prostate cancer and chemotherapy.

PMID- 16985597
TI  - Vitamin C supplementation and urinary oxalate excretion.

PMID- 16985598
TI  - High-grade prostatic intraepithelial neoplasia.
AB  - High-grade prostatic intraepithelial neoplasia is considered the most likely
      precursor of prostatic carcinoma. The only method of detection is biopsy;
      prostatic intraepithelial neoplasia (PIN) does not significantly elevate serum
      prostate-specific antigen concentration and cannot be detected by ultra
      sonography. The incidence of PIN in prostate biopsies averages 9% (range, 4%
      16%), representing 115,000 new cases of PIN diagnosed each year in United States.
      PIN has a high predictive value as a marker for adenocarcinoma, and its
      identification warrants repeated biopsy for concurrent or subsequent invasive
      carcinoma. Carcinoma will develop in most patients with PIN within 10 years. PIN
      is associated with progressive abnormalities of phenotype and genotype that are
      intermediate between normal prostatic epithelium and cancer, indicating
      impairment of cell differentiation and regulatory control with advancing stages
      of prostatic carcinogenesis. Androgen deprivation therapy decreases the
      prevalence and extent of PIN, suggesting that this form of treatment may play a
      role in chemoprevention.

PMID- 16985599
TI  - Evaluation and surgical management of intrinsic sphincter deficiency after
      radical prostatectomy.
AB  - Urinary incontinence following prostatectomy is usually due to intrinsic
      sphincter deficiency and is often referred to as post-prostatectomy incontinence
      (PPI). The male sling is an effective minimally invasive procedure for low volume
      PPI. Although the male sling procedure is becoming increasingly popular, the
      artificial urinary sphincter (AUS) remains the gold standard. Placement of the
      AUS cuff using the transcorporal technique salvages patients with urethral
      atrophy as well as prior AUS erosion or infection. As the surgical options for
      PPI expand, it is important to analyze the outcomes with contemporary surgical
      techniques and to develop an algorithm for procedure selection.

PMID- 16985600
TI  - Preventing progression in men with mild symptoms of benign prostatic hyperplasia:
      a potential role for phytotherapy.
AB  - Prevalence of benign prostate hyperplasia (BPH) is increasing with the aging
      population worldwide. Throughout the 20th century, men with minimally symptomatic
      BPH were generally advised to defer treatment. Treatment deferral or watchful
      waiting has always appeared reasonable because mild lower urinary tract symptoms
      suggestive of bladder outlet obstruction are not bothersome and are often
      regarded as part of the aging process, progression is usually slow, and symptoms
      often regress spontaneously. This review examines the evidence of the natural
      history of BPH, highlighting the group of patients with mild symptoms, the risk
      factors for progression, and the potential role of phytotherapy in this group of
      men.

PMID- 16985602
TI  - Interstitial cystitis: the paradigm shifts: international consultations on
      interstitial cystitis.

PMID- 16985601
TI  - Report from the society of urologic oncology: highlights from the fourth annual
      meeting of the society of urologic oncology, december 5-6, 2003, bethesda, MD.

PMID- 16985603
TI  - The role of routine serum testosterone testing: routine hormone analysis is not
      indicated as an initial screening test in the evaluation of erectile dysfunction.
AB  - A 60-year-old male physician is self-referred to your office for evaluation of
      his erectile dysfunction, which has been worsening for 5 years. He reports his
      erections rarely achieve fullness for penetration, and he is unable to ejaculate.
      He has tried sildenafil citrate (Viagra(R); Pfizer Inc, New York, NY) with mild
      success in the past. He has a strong libido and feels healthy. He rarely
      exercises, but is on his feet most of the day at work. He has been healthy his
      whole life and never seeks a doctor's attention. He has no other medical
      problems. His only medication is a baby aspirin once a day. His physical
      examination, including genitalia, is normal. As part of his initial visit, should
      his serum testosterone level be checked by his urologist?

PMID- 16985605
TI  - Genetic testing of infertile patients.

PMID- 16985604
TI  - The role of serum testosterone testing: routine hormone analysis is an essential
      part of the initial screening of men with erectile dysfunction.
AB  - As oral phosphodiesterase-5 inhibitor therapy has become the first-line treatment
      of erectile dysfunction (ED), common approaches in the evaluation of ED have been
      largely abandoned. Not only is routine hormone analysis no longer widely
      recommended, but most specialists perform serum testosterone level testing only
      in the most complex cases of ED. This article explores the rationale for
      including serum testosterone analysis as part of the initial screening of
      patients with ED. The use of routine serum testosterone testing is advocated for
      its efficacy in the diagnosis and treatment of hypogonadism and pituitary
      disorders associated with ED.

PMID- 16985607
TI  - New Drug under Development for Stress and Urge Urinary Incontinence.

PMID- 16985606
TI  - Obesity and prostate cancer detection and progression.

PMID- 16985608
TI  - Management of localized prostate cancer.

PMID- 16985609
TI  - Letter from the editors: reviews in urology.

PMID- 16985610
TI  - The congenital and acquired solitary kidney.
AB  - The embryonic insult that results in unilateral renal agenesis may involve not
      only the ureteral bud but also other mesonephric duct derivatives, including the
      seminal vesicles, vas deferens, and epididymis; in the female with a solitary
      kidney, mullerian duct anomalies frequently occur. Normal renal development
      depends upon a normal ureteral bud, which undergoes orderly branching and
      penetrates the metanephric blastema at about the fifth week of gestation.
      Ureteral and kidney development are thought to be interdependent, and when there
      is failure of the ureteral bud to form or absence of the nephrogenic ridge, the
      kidney does not develop normally. Unilateral renal agenesis is compatible with
      normal longevity and does not predispose the contralateral kidney to greater-than
      normal risk; nevertheless, patients should have annual surveillance, including a
      blood pressure measurement, serum creatinine if not initially normal, and
      urinalysis to detect proteinuria. Removal of one kidney leads to structural and
      functional changes by the remaining kidney, including increased filtration of the
      remaining glomeruli. These functional changes have generally been considered
      beneficial because they mitigate the reduction in the total glomerular filtration
      rate that would otherwise occur, but experimental evidence suggests that these
      changes may have an adverse effect on the remaining kidney. Clinical evidence
      shows that these changes do not lead to renal deterioration in kidney donors
      because the renal function of kidney donors is well preserved in over 20 years of
      follow-up after donor nephrectomy.

PMID- 16985611
TI  - Laparoscopic total and partial nephrectomy-the new standard?
AB  - Laparoscopic radical nephrectomy has been shown in long-term follow-up to provide
      shorter patient hospitalization and effective cancer control with no significant
      difference in survival compared with open radical nephrectomy. The major
      technical issue for success of laparoscopic partial nephrectomy is hemostatic
      control, and several techniques have been developed to improve control.
      Laparoscopic partial nephrectomy continues to evolve along two therapeutic
      technical avenues: hilar clamping with ischemia versus no hilar clamping. The
      benefits of laparoscopy for the kidney have clearly been demonstrated in terms of
      less pain, decreased convalescence, and decreased narcotic requirements. With
      short-term outcomes demonstrating laparoscopic partial nephrectomy as an
      efficacious procedure, the role of laparoscopic partial nephrectomy should
      continue to increase.

PMID- 16985612
TI  - Artificial neural networks for decision-making in urologic oncology.
AB  - Artificial neural networks (ANNs) are computational methodologies that perform
      multifactorial analyses, inspired by networks of biological neurons. Like neural
      networks, ANNs contain layers of simple points (nodes) of data that interract
      through carefully weighted connection lines. ANNs are "trained" and balanced by
      having been previously fed data, which the ANN uses as the means for adjusting
      its interconnections. Studies have shown that novel and highly accurate ANNs
      significantly enhance the ability to detect prostate cancer early (high
      sensitivity) while avoiding a greater number of unnecessary tissue samplings
      (high specificity). The use of ANNs in prostate cancer is ideal because of 1)
      multiple predicting factors that influence outcome; 2) the desire to offer
      individual consulting based on various tests; 3) the fact that prior logistic
      regression analysis results have had serious limitations in application; and 4)
      the need for an up-to-date tool that can apply easily to everyone. An ANN should
      be seen as an important tool that is complementary to the physician's personal
      knowledge and judgment in making decisions.

PMID- 16985613
TI  - Increasing awareness and improving the care of urinary incontinence: highlights
      from the world health organization 2nd international consultation on incontinence
      july 1-4, 2001, paris, france.

PMID- 16985614
TI  - Urologic oncology: extraordinary opportunities for discovery: highlights from the
      2nd annual winter meeting of the society of urologic oncology december 1-2, 2001,
      bethesda, MD.

PMID- 16985615
TI  - Surgical, Pharmacological, and Technological Advances in Adult and Pediatric
      Urology-State of the Art: Highlights of the 8th Annual NYU Department of Urology
      Post-Graduate Course December 6-8, 2001, New York, NY.

PMID- 16985616
TI  - Selecting Treatment for Distal Ureteral Calculi: Shock Wave Lithotripsy versus
      Ureteroscopy.
AB  - Shock wave lithotripsy (SWL) and ureteroscopy (URS) are both effective treatments
      for removal of distal ureteral calculi, associated with high success rates and
      limited morbidity. The American Urological Association Ureteral Stones Clinical
      Guidelines Panel has found both to be acceptable treatment options for patients,
      based on the stone-free results, morbidity, and retreatment rates for each
      respective therapy. However, costs and patient satisfaction or preference were
      not addressed, and the report was based on data derived from older endoscopic and
      lithotripsy technology. Each of these treatment options has valid advantages and
      disadvantages. Both modalities are reasonable treatment options for the majority
      of patients with distal ureteral calculi. Whereas SWL is less invasive, the high,
      immediate success rate with minimal morbidity and decreased cost makes URS a very
      valid competitor. The results of treating patients with larger stones favor URS.

PMID- 16985617
TI  - 54-year-old male with high-grade prostatic intraepithelial neoplasia on prostate
      biopsy.

PMID- 16985618
TI  - Urothelial carcinoma in a man with hereditary nonpolyposis colon cancer.
AB  - Although most upper tract urothelial carcinomas are believed to be acquired,
      patients with hereditary nonpolyposis colon cancer (HNPCC) may have more than 20
      times the risk of the normal population for these cancers. Certain mismatch
      repair mutations are now known to be associated with the disease. Screening and
      surveillance regimens are still evolving, but urinalysis, urine cytology,
      cystoscopy, and periodic upper tract imaging are the mainstays. HNPCC should be
      considered in any patient who develops an upper tract urothelial cancer or has a
      suggestive family history.

PMID- 16985619
TI  - Peripheral blood rt-PCR assays for detection and prognosis of prostate cancer.

PMID- 16985620
TI  - New approaches to the treatment of overactive bladder: the purine pathways and an
      update on the tension-free vaginal tape sling.

PMID- 16985621
TI  - Normal-calcium, low-sodium, and low-animal-protein diet for stone prevention.

PMID- 16985622
TI  - Chemoprevention and prostate cancer.

PMID- 16985623
TI  - Vaccine therapy for renal cell carcinoma.
AB  - Several potential vaccines have been evaluated for the treatment of patients with
      renal cell carcinoma (RCC). They include dendritic cells pulsed with tumor
      lysate, a dendritic cell-tumor cell hybrid, irradiated tumor cells admixed with
      adjuvants, and a heat shock protein-peptide complex. Promising results have been
      obtained in several early clinical trials, but issues of tumor immunosuppression
      and lack of identified tumor-associated antigens must be addressed before vaccine
      therapy can be applied successfully in advanced RCC. In this patient population,
      vaccine therapy will likely be required in combination with other forms of
      immunotherapy, such as interleukin-2 and thalidomide. In contrast, vaccine
      therapy alone may be sufficient for high-risk patients in the adjuvant setting.

PMID- 16985624
TI  - Quality of life and sexual function in patients with benign prostatic
      hyperplasia.
AB  - Incidence of benign prostatic hyperplasia (BPH), one of the most common
      conditions affecting adult men, increases dramatically after the age of 50. The
      various symptoms of BPH, which include lower urinary tract symptoms (LUTS), can
      adversely affect quality of life (QOL). Many men with BPH and LUTS wait until
      symptoms become significantly bothersome before seeking medical attention.
      Evaluating the exact severity and significance of symptoms has been difficult
      with previous methodology. Over the last decade, assessment tools have become
      available to quantify the symptoms of BPH and LUTS. This article addresses the
      impact of BPH, its management, and the overall effects it has on QOL.

PMID- 16985625
TI  - Modern Tumor Marker Discovery in Urology: Surface Enhanced Laser Desorption and
      Ionization (SELDI).
AB  - During the last two decades, biomarker research has benefited from the
      introduction of new proteomic analytical techniques. In this article, we review
      the application of surface enhanced laser desorption/ionization time-of-flight
      (SELDI-TOF) mass spectroscopy in urologic cancer research. After reviewing the
      literature from MEDLINE on proteomics and urologic oncology, we found that SELDI
      TOF is an emerging proteomic technology in biomarker discovery that allows for
      rapid and sensitive analysis of complex protein mixtures. SELDI-TOF is a novel
      proteomic technology that has the potential to contribute further to the
      understanding and clinical exploitation of new, clinically relevant biomarkers.

PMID- 16985626
TI  - Advances in the Medical Treatment of Prostate Cancer, Bladder Cancer, Renal Cell
      Cancer, and Benign Prostatic Hyperplasia: Highlights from the XVIIth Congress of
      the European Association of Urology, Birmingham, UK, February 23-26, 2002.

PMID- 16985628
TI  - Recent findings in impotence research: 10th world congress of the international
      society for sexual and impotence research, montreal, Canada, september 22-26,
      2002.

PMID- 16985627
TI  - Advances in prostate cancer treatment: highlights from the 2nd international
      prostate cancer congress, st. Thomas, u.s. Virgin islands, july 17-20, 2002.

PMID- 16985629
TI  - Management of vesicoureteral reflux.
AB  - Four cases of vesicoureteral reflux are discussed by prominent pediatric
      urologists. The condition can range from minimal reflux into the distal ureter to
      massive reflux causing tortuosity of the ureter and hydronephrosis. Treatment
      options range from medical management to tapering of the ureter with
      reimplantation. The cross-trigonal technique is popular among pediatric
      urologists, and the Politano-Leadbetter technique is a very successful technique
      that has stood the test of time. The extravesical approach to ureteral
      reimplantation reduces morbidity, shortens hospital stays, reduces medical costs,
      and maintains the high success rates of the intravesical techniques. Subureteric
      injection of bulking agents to correct the reflux holds promise as an alternative
      to open surgery, but presents the challenge of identifying the ideal bulking
      agent.

PMID- 16985630
TI  - 20-year-old male with recurrent right flank pain.

PMID- 16985631
TI  - Hormone replacement therapy and postmenopausal stone-formers.

PMID- 16985632
TI  - The estrogen controversy.

PMID- 16985633
TI  - Management of urinary tract infections in children: simplifying the
      controversies?

PMID- 16985634
TI  - Pharmacotherapy for stress urinary incontinence.
AB  - The purpose of this review article is to highlight new pharmacotherapies on the
      horizon for the treatment of stress urinary incontinence. Although behavioral and
      surgical therapies are currently the mainstay of treatment for this condition, we
      are hopeful that pharmacotherapy will one day take center stage of the various
      treatment options. Currently, there are no medications approved by the US Food
      and Drug Administration for the treatment of stress urinary incontinence.
      However, exciting clinical data are becoming available about an oral medication
      for the treatment of stress urinary incontinence that appears to be clinically
      safe and efficacious. In addition to discussing medications currently under
      development, this article also discusses pharmacologic targets that could be
      suitable future targets to treat stress urinary incontinence.

PMID- 16985635
TI  - Peyronie's Disease: A Review.
AB  - Peyronie's disease is an acquired benign condition without known systemic
      sequelae with presenting symptoms that include the presence of a plaque or
      induration of the penile shaft, penile curvature or deformity during erection,
      penile pain, and erectile dysfunction. This article reviews the natural history
      of the disease, discusses the disease's etiology (widely thought to involve minor
      penile trauma with subsequent aberrant wound healing), and outlines proper
      clinical evaluation of Peyronie's disease patients. Medical treatments can be
      systemic (colchicine, potassium aminobenzoate, vitamin E), intralesional
      (steroids, verapamil, collagenase, interferons), or topical. Surgical therapy for
      Peyronie's disease (plication, graft-based, and prosthetic techniques) should be
      reserved for the man who has failed conservative therapy and whose curvature,
      indentation, or erectile dysfunction precludes intercourse. Regardless of the
      surgical procedure, the patient should be made aware of the inherent risks of
      surgery.

PMID- 16985636
TI  - Optimizing prostate biopsy strategies for the diagnosis of prostate cancer.
AB  - The importance of prostate biopsy in urologic practice has been magnified by the
      routine use of serum prostate-specific antigen in prostate cancer screening.
      Given the potential impact of the procedure on both patient care and health care
      costs, an optimal strategy for accurate and judicious detection of early prostate
      cancer is imperative. Maintaining maximal sensitivity and negative predictive
      value are equally important to the patient. In this article, we review recent
      modifications in prostate biopsy indications and techniques that may allow for a
      systematic biopsy approach to the patient in whom prostate cancer is suspected.

PMID- 16985638
TI  - Updates in Endourology and Shock Wave Lithotripsy: Highlights from the 20th World
      Congress on Endourology and SWL, 18th Basic Science Research Symposium, September
      19-22, 2002, Genoa, Italy.

PMID- 16985637
TI  - Best of the 2003 AUA Annual Meeting: Highlights from the 2003 Annual Meeting of
      the American Urological Association, April 26-May 1, 2003, Chicago, IL.

PMID- 16985639
TI  - Updates in Pediatric Urology: Highlights from the American Academy of Pediatrics
      Section on Urology Annual Meeting, October 18-21, 2002, Boston, MA.

PMID- 16985640
TI  - Role of lymphadenectomy for patients undergoing radical nephrectomy for renal
      cell carcinoma.
AB  - The potential benefits of a lymph node dissection (LND) include more accurate
      staging, decreased local recurrence rates, and improved survival. However, only
      limited data support the potential benefits of routine, extensive LND for renal
      cell carcinoma (RCC). Because of lack of data, no clear practice standard has
      been established about whether to perform LND and, if so, to what extent. The
      value of LND for RCC is only relevant if the pattern of lymphatic spread is
      predictable, which it is not. However, although little evidence supports the
      value of LND for RCC, it is probable that an occasional patient will have very
      early metastasis confined to the area of the primary and secondary major
      lymphatic flow medially and perhaps will benefit therapeutically. In this case, a
      limited LND is supportable. No information currently available strongly supports
      the value of a more extensive and potentially more morbid LND for either staging
      or therapeutic value. Extensive investigation is necessary in order to establish
      LND as a standard component of RCC surgery.

PMID- 16985641
TI  - Lymph node dissection in patients with kidney cancer: when is it indicated?
AB  - It is necessary to consider the potential risks and benefits of performing a
      lymph node dissection (LND) at the time of radical nephrectomy. LND may lead to
      more accurate staging, a decrease in local recurrence, and an increase in
      survival for patients with metastatic disease limited to the resected lymph
      nodes. However, there are risks associated with the treatment that must be
      considered. The advantages of LND vary among patients, depending on the location
      and extent of disease progression. For patients with stage T3 or T4 disease, we
      recommend a limited LND. Patients with T3 or T4 disease with grossly positive
      nodes with or without hematogenous metastasis should undergo a more extensive
      LND.

PMID- 16985642
TI  - Male infertility.

PMID- 16985643
TI  - Bisphosphonates in metastatic prostate cancer.

PMID- 16985644
TI  - Androgen replacement and quality of life.

PMID- 16985645
TI  - Late relapse of germ-cell tumor.

PMID- 16985646
TI  - The future of bladder control-intravesical drug delivery, a pinch of pepper, and
      gene therapy.
AB  - The incidence of urinary incontinence and overactive bladder problems will
      continue to grow as the population ages. Future treatments are likely to include
      an implantable drug delivery system, gene therapy, and the intravesical use of
      the vallinoids capsaicin and resiniferatoxin (RTX). An understanding of the
      urothelium is essential for effective design of these therapies. Intravesical
      anticholinergic drug treatment is currently not widely used, but intravesical
      pumps are under development to provide less cumbersome treatment methods and will
      provide nonsurgical options for patients who cannot tolerate oral anticholinergic
      agents. Research on the use of capsaicin as an intravesicular drug has had
      limited success, but trials have confirmed the efficacy of intravesical capsaicin
      for detrusor hyperreflexia. RTX is as effective as capsaicin but without side
      effects, such as pain and inflammatory neuropeptide release. RTX treatment may
      eliminate the need for surgical and other drug treatments of lower urinary tract
      dysfunction in patients with spinal cord injuries. Gene therapy will change the
      practice of urology by addressing the deficiencies that cause symptoms rather
      than attacking the symptoms themselves.

PMID- 16985647
TI  - Laparoscopic prostatectomy: where do we stand?
AB  - Laparoscopic radical prostatectomy is an effective treatment for localized
      prostate cancer. This cost-intensive and technically demanding operation
      currently takes longer than the standard open procedures, but with increasing
      experience, it is eventually associated with lower costs and is nearly as fast.
      As more urologists gain such experience, the laparoscopic approach may challenge
      the standard approaches.

PMID- 16985649
TI  - Surgical, Pharmacological, and Technological Advances in Adult and Pediatric
      Urology - State of the Art: Highlights of the 7th Annual NYU Department of
      Urology Postgraduate Course December 7-9, 2000, New York, NY.

PMID- 16985648
TI  - Sural Nerve Interposition Grafting during Radical Prostatectomy.
AB  - In 1997, autologous sural nerve grafting to reconstruct bilaterally resected
      cavernosal nerves was successfully performed in patients undergoing radical
      retropubic prostatectomy. After 12 months, one third of these patients had
      erections sufficient for intercourse. Since that time, patients who have had
      neurovascular bundle resection and sural nerve grafting have continued to show
      promising results. For example, within one large cohort of men who had
      unilateral, nerve-sparing radical prostatectomy, significantly more men who had
      sural nerve grafting regained potency, and did so in less time, than men who did
      not have grafting. More importantly, however, with better predictions of the
      presence of extracapsular disease, nerve-sparing surgery can be performed more
      selectively, reserving wide resection and sural nerve grafting for patients
      likely to have extracapsular extension. A multicenter, randomized clinical trial
      is needed to substantiate the positive outcomes observed with sural nerve
      grafting.

PMID- 16985650
TI  - Laparoscopic radical nephrectomy: morcellate or leave intact? Definitely
      morcellate!
AB  - Eleven years after the first laparoscopic radical nephrectomy (LRN), which was
      performed with morcellation, the best approach to the procedure remains
      controversial. Concerns include tumor seeding, recurrence, accuracy of staging,
      histopathological diagnosis, and longer surgery time. Enclosing the kidney in an
      impermeable sac prior to morcellation helps prevent seeding. Pathological review
      of morcellated LRN specimens has been shown to be as accurate as that of intact
      specimens. Ten-year survival data for LRN with morcellation are not available
      yet, but 5-year rates are as good as those for open nephrectomy. The utility of
      morcellation in LRN is supported by the results of clinical practice.

PMID- 16985651
TI  - Laparoscopic radical nephrectomy: morcellate or leave intact? Leave intact.
AB  - At specialized centers worldwide, laparoscopic radical nephrectomy is now routine
      practice for management of indicated patients with localized renal cell
      carcinoma. Although the various intraoperative technical steps and maneuvers have
      been standardized for both the retroperitoneal and the transperitoneal
      laparoscopic approaches, controversy persists regarding the method of extraction
      of the nephrectomized cancerous specimen. Opinion is divided between intact
      extraction and morcellation. Clearly, the larger skin incision used for intact
      extraction is a cosmetic compromise. However, available data suggest that patient
      morbidity is not adversely impacted to any significant degree. Intact specimen
      extraction does build confidence into this procedure by respecting scientifically
      established oncologic guidelines, and it provides a specimen identical to that
      obtained in open surgery. This facilitates accurate pathologic staging, including
      assessment of surgical margins, which allows formulation of individualized,
      patient-specific follow-up protocols. For these reasons, intact extraction for
      renal cell cancer is preferred at our institution and multiple others worldwide.

PMID- 16985652
TI  - Case scenario: 26-year-old male with right scrotal pain and swelling.

PMID- 16985653
TI  - Incontinence in a child with a duplex kidney: case report.
AB  - Persistent incontinence after toilet training in young girls and urinary tract
      infections or epididymitis in prepubertal boys should raise suspicion of an
      ectopic ureter. This often occurs in the context of duplication of kidney
      structures or other parenchymal abnormalities. The presence or absence of reflux
      affects surgical treatment, which may consist of ureteral reimplantation,
      ureteroureterostomy, and/or upper pole nephrectomy.

PMID- 16985654
TI  - Using electrical stimulation for urinary incontinence.

PMID- 16985655
TI  - Recurrent uncomplicated urinary tract infections: can young women diagnose and
      treat themselves?

PMID- 16985656
TI  - Reconsideration of the 1988 NIH Consensus Statement on Prevention and Treatment
      of Kidney Stones: Are the Recommendations Out of Date?
AB  - In 1988, a consensus conference was held at the National Institutes of Health to
      develop guidelines for prevention and treatment of kidney stones. The
      recommendations regarding the medical evaluation of stone formers and treatment
      directed at stone prevention are reviewed. The relevance of those 1988 guidelines
      is evaluated for continued pertinence. Most of the recommendations promulgated in
      the consensus statement remain useful today. One significant change is the
      current consensus that dietary calcium restriction is no longer considered
      appropriate therapy, as there is no evidence that it actually prevents stones and
      has as a consequence the potential to worsen bone demineralization.

PMID- 16985657
TI  - Botulinum toxin: poisoning the spastic bladder and urethra.
AB  - Botulinum toxin has proven to be a safe and effective therapy for a variety of
      somatic and autonomic motor disorders. Urologists are now finding clinical
      success with urethral and bladder injection of this fascinating toxin for
      detrusor sphincter dyssynergia, conditions of pelvic floor spasticity, and
      overactive bladder. One cannot deny the ingenuity of man in transforming the
      lethal toxin of Clostridium botulinum into a modern day therapeutic medicine.

PMID- 16985658
TI  - Chemoprevention strategies in the prostate: an overview.
AB  - Chemoprevention is the administration of agents (drugs, biologics, and nutrients)
      to prevent induction, inhibit, or delay the progression of cancers. Prostate
      cancer is an important target for chemoprevention because of its long latency and
      high prevalence. The development of rational chemopreventive strategies requires
      knowledge of the mechanisms of prostate carcinogenesis and identification of
      agents that interfere with these mechanisms. Because of the long time period for
      prostate carcinogenesis and the large size of the cohort required for an
      evaluable study, identification and characterization of early intermediate
      biomarkers and their validation as surrogate endpoints for cancer incidence are
      essential for chemopreventive agent development. Finally, suitable populations
      with appropriate risk factors, including the presence of premalignant lesions and
      genetic predispositions, need to be well characterized for future chemopreventive
      interventions.

PMID- 16985660
TI  - Radiation therapy after radical prostatectomy: strike early, strike hard! The
      case for adjuvant radiation therapy.
AB  - With a large local tumor, when surgical extirpation results in a positive
      surgical margin, adjuvant radiotherapy is the routine approach for a variety of
      solid tumors, such as head and neck cancers, rectal cancer, lung cancer, and
      breast cancer. With prostate cancer, however, surgery and radiotherapy are
      considered as alternative single-modality treatments, and their combination is
      far less enthusiastically embraced. Despite a trend toward earlier clinical
      diagnosis of prostate cancer since the introduction of prostate-specific antigen
      (PSA) screening, modern surgical series continue to show a 15%-25% incidence of
      positive surgical margins. Postoperative radiotherapy, whether delivered as
      "adjuvant therapy" shortly after surgery or as "salvage therapy" when serum PSA
      becomes detectable, effectively improves local control and prolongs disease-free
      survival.

PMID- 16985659
TI  - Urology Update from Jackson Hole: Highlights from the 3rd Annual Jackson Hole
      Summer Urologic Conference July 28-August 3, 2001, Jackson Hole, WY.

PMID- 16985661
TI  - Radiation therapy after radical prostatectomy: why patience is a virtue! The case
      for salvage radiation therapy.
AB  - Without reliable clinical or pathologic predictors of local recurrence, selection
      of patients for adjuvant radiotherapy based on any combination of clinical or
      pathological parameters is bound to lead to the unnecessary treatment of
      significant numbers of patients whose disease might not have ultimately recurred
      or who might have been destined to have recurrence with extrapelvic metastatic
      disease, for which pelvic radiation would be ineffective. Furthermore, new
      ultrasensitive prostate-specific antigen (PSA) assays can identify patients
      actually failing surgery with a detectable and rising PSA earlier than ever, when
      disease volume is low and still amenable to salvage radiation therapy, and can
      allow the calculation of the PSA doubling time, which is gaining widespread
      acceptance as a proven predictor of response to salvage radiation therapy in this
      setting. Therefore, the rationale for preemptive adjuvant radiation therapy after
      radical prostatectomy is weaker than ever.

PMID- 16985662
TI  - Prostatitis/Chronic pelvic pain syndrome.

PMID- 16985663
TI  - Metastatic transitional cell carcinoma of the urinary bladder to the shoulder
      girdle.
AB  - Transitional cell carcinoma (TCC) of the bladder typically metastasizes to the
      pelvic lymph nodes and to visceral sites including the lungs, liver, and bones.
      Other sites include the brain, especially after systemic chemotherapy. To our
      knowledge, we report the first case of TCC metastatic to the soft tissue of the
      shoulder girdle and discuss common and unusual sites of metastasis in TCC.

PMID- 16985664
TI  - Management alternatives for vesicoureteral reflux.

PMID- 16985665
TI  - Timing of Sperm Retrieval in ICSI-IVF.

PMID- 16985666
TI  - Laparoscopic and percutaneous ablative techniques in the treatment of renal cell
      carcinoma.
AB  - Widespread use of computed tomography, ultrasound, and magnetic resonance imaging
      has led to an increase in detection of relatively small renal masses, and
      approaches to managing them have evolved in the last two decades. Indications for
      nephron-sparing surgery have expanded, and minimally invasive procedures, which
      can confer advantages over open surgery, are now available. Ablative techniques
      offer a combination of nephron-sparing and minimally invasive approaches.
      Ablative techniques include cryoablation, radiofrequency ablation (RFA), and high
      intensity focused ultrasound (HIFU). Cryoablation and RFA have been relatively
      safe. HIFU has been associated with serious side effects in animal models, and is
      not yet acceptable for use in humans. Ablative techniques require long-term
      studies to confirm lasting efficacy. The best modality for tumor targeting,
      monitoring of therapy, and follow-up is still under investigation. Debate exists
      regarding the best method for ensuring adequate intraoperative tumor
      cryoablation. For minimally invasive ablative measures to gain a place as nephron
      sparing approaches, they should show both equivalent efficacy and reduced
      morbidity relative to those of open partial nephrectomy. These techniques should
      currently be reserved for selected patients and should be compared to the
      evolving modality of laparoscopic partial nephrectomy.

PMID- 16985668
TI  - Best of the 2002 AUA Annual Meeting: Highlights of the 2002 Annual Meeting of the
      American Urological Association May 25-30, 2002, Orlando, FL.

PMID- 16985667
TI  - Interstitial cystitis: characterization and management of an enigmatic urologic
      syndrome.
AB  - The enigmatic urologic condition known as interstitial cystitis has an estimated
      prevalence of 0.01% to 0.50% of the female population. Its etiology is unknown
      but may involve microbiologic, immunologic, mucosal, neurogenic, and/or other, as
      yet undefined, agents. There is no gold standard for the diagnosis of
      interstitial cystitis; rather, it is a diagnosis of exclusion. It is impossible
      to provide a purely evidence-based treatment strategy, but review of available
      evidence suggests that conservative supportive therapy (including diet
      modification); oral treatment with pentosan polysulfate, amitriptyline,
      hydroxyzine, or cimetidine; and intravesical treatments with heparinoids,
      dimethyl sulfoxide, alkalized lidocaine, or bacille Calmette-Guerin may be
      effective in some patients.

PMID- 16985669
TI  - Selecting treatment for high-risk, localized prostate cancer: the case for
      radiation therapy.
AB  - Prostate cancers that clinically appear to be localized may nonetheless respond
      poorly to curative treatment. Pretreatment prostate-specific antigen (PSA) level,
      biopsy Gleason score, and percentage of positive biopsies are all at least as
      important as clinical stage in predicting treatment outcome. A patient with a
      nonpalpable tumor, stage T1c disease, serum PSA of 12 ng/mL, and a Gleason score
      of 8 to 10 in 2 of 12 biopsy cores has a relatively poor prognosis. In a high
      risk patient such as this one, the recommended treatment strategy involves a
      combination of brachytherapy and conformal external beam radiotherapy. In studies
      comparing treatments in patients stratified according to a variety of risk
      measures, this combination has shown biochemical disease-free survival rates
      superior to those seen following radical prostatectomy. The role of androgen
      suppression remains unclear.

PMID- 16985670
TI  - Selecting treatment for high-risk, localized prostate cancer: the case for
      radical prostatectomy.
AB  - The most common treatment options for men with clinically localized prostate
      cancer include radical prostatectomy and radiation therapy. The choice between
      these options is often controversial, and selecting the optimal treatment poses a
      great challenge for patients and physicians. Factors important to the decision
      include age and life expectancy of the patient, the natural history of the
      prostate cancer, how curable the disease is, and the morbidity of treatment. Use
      of these criteria to select treatment for a healthy, 70-year-old man presenting
      with a nonpalpable tumor, stage T1c disease, serum prostate-specific antigen of
      12 ng/mL, and an adenocarcinoma with a Gleason score of 8 that is present in 2 of
      12 biopsy cores would lead to the choice of radical prostatectomy over radiation
      therapy. Data show that such a patient has a life expectancy of more than 12.3
      years if the prostate cancer can be cured and a high probability of dying from
      the disease if it is not cured. Data further show that radical prostatectomy in
      such a patient would confer a survival advantage over radiation therapy without
      resulting in greater complications or reduction in quality of life.

PMID- 16985671
TI  - Case scenario: 69-year-old male with left spermatic cord mass.

PMID- 16985672
TI  - High-grade prostatic intraepithelial neoplasia on a prostate biopsy-what does it
      mean?

PMID- 16985673
TI  - Antibiotic prophylaxis for urodynamics and estrogen therapy for urinary
      incontinence.

PMID- 16985674
TI  - Assessing quality of life following radiotherapy.

PMID- 16985676
TI  - The picture of the prostatic lymphokine network is becoming increasingly complex.
AB  - The immunology of the prostate has recently developed into a new field of
      research in urology. Although we do not yet understand why the leukocyte
      population increases, we know that most resected prostate tissue shows signs of
      an inflammatory reaction. Different types of inflammation exist, and must be
      distinguished carefully according to distribution and location of leukocytes and
      histology of the surrounding tissue. This article reviews recent findings and
      discusses the complex mechanisms involved in the prostatic inflammatory response.
      The roles of estrogen, interleukin (IL)-6, IL-8, IL-15, and IL-17 are examined.

PMID- 16985675
TI  - Paraneoplastic syndromes in urologic malignancy: the many faces of renal cell
      carcinoma.
AB  - Renal cell carcinoma is unique among the genitourinary malignancies in that close
      to one third of affected patients show signs and symptoms of a paraneoplastic
      syndrome. The paraneoplastic syndromes associated with renal cell carcinoma range
      from those manifesting in constitutional symptoms (ie, fever, cachexia, and
      weight loss) to those that result in specific metabolic and biochemical
      abnormalities (ie, hypercalcemia, nonmetastatic hepatic dysfunction, amyloidosis,
      etc). The presence of a paraneoplastic syndrome in a patient with renal cell
      carcinoma is neither a marker of metastatic disease nor necessarily indicative of
      a poor prognosis. The importance of understanding the pathophysiology and biology
      behind the many paraneoplastic syndromes associated with renal cell carcinoma
      lies in the fact that the presence of these protean symptoms may be the initial
      presentation of either primary or recurrent disease. In this review, we will
      describe the proposed mechanisms of action of the many paraneoplastic syndromes
      associated with renal cell carcinoma as well as outline the clinical evaluation
      and treatment options currently available for these noteworthy disorders.

PMID- 16985678
TI  - Updates in Pediatric Urology: Highlights from the American Academy of Pediatrics
      Section on Urology Annual Meeting October 20-24, 2001, San Francisco, CA.

PMID- 16985677
TI  - The treatment of lower pole renal calculi in 2003.
AB  - The optimal treatment of patients with lower pole renal calculi is still being
      defined. Shock wave lithotripsy, percutaneous nephrolithotomy, and ureteroscopy
      are all currently utilized to treat patients with this condition. These methods
      have yielded varying degrees of success. The influence of collecting system
      anatomy on shock wave lithotripsy results remains controversial. Ongoing
      randomized, prospective trials evaluating the efficacy of all of these respective
      therapeutic options will, it is hoped, determine the best approaches for this
      patient cohort.

PMID- 16985679
TI  - 72-year-old woman with urinary hesitancy and pelvic pain.

PMID- 16985680
TI  - Juxtaglomerular apparatus tumor: a rare, surgically correctable cause of
      hypertension.
AB  - Although uncommon, presentation of juxtaglomerular cell tumor is distinct and
      should allow a correct preoperative diagnosis in most patients. Typical clinical
      presentations include headaches, polyuria, or isolated, asymptomatic, severe
      hypertension. The diagnosis of a juxtaglomerular apparatus (JGA) tumor typically
      results from identification of plasma renin levels two- to sevenfold greater than
      the normal value. Although JGA tumors are considered benign, with no reports of
      metastases or recurrence, they are potentially lethal if left untreated. Surgical
      excision is curative.

PMID- 16985681
TI  - Immunological based therapies for urinary tract infection: the future is almost
      here!

PMID- 16985682
TI  - Prescribing PDE5 Inhibitors: Who Is the "Normal" Man?

PMID- 16985683
TI  - Evolving Role of Pro-PSA as a New Serum Marker for the Early Detection of
      Prostate Cancer.

PMID- 16985684
TI  - Testicular microlithiasis, chemotherapy for stage I seminoma, and chemotherapy
      for advanced extragonadal germ cell tumors.

PMID- 16985685
TI  - Current and Coming in Endourology: Highlights of the 18th World Congress on
      Endourology and SWL and the 16th Basic Research Symposium September 14-17, 2000,
      Sao Paulo, Brazil.

PMID- 16985686
TI  - Update in pediatric urology: highlights from the annual meeting of the american
      academy of pediatrics section on urology november 28-29, 2000, chicago.

PMID- 16985687
TI  - International Symposium on UTI Management: Highlights of an international
      symposium on Advances in Urinary Tract Infection Management March 9-12, 2000,
      Orlando, Fla.

PMID- 16985688
TI  - Caseating granulomas on the glans penis as a complication of bacille calmette
      guerin intravesical therapy.
AB  - Intravesical instillation of bacille Calmette-Guerin (BCG) in patients with
      superficial bladder cancer or with carcinoma in situ of the bladder is a
      frequently used therapeutic option. As with other cancer therapies, BCG
      instillation has its share of side effects and complications. This case report
      highlights an uncommon complication.

PMID- 16985689
TI  - Conservative management of a grade 4 renal laceration in a child.
AB  - Renal trauma associated with blunt abdominal trauma is common. Children
      presenting with grade 4 or 5 renal lacerations who are hemodynamically stable can
      be followed safely nonoperatively. No long-term complications from conservative
      management have been noted.

PMID- 16985690
TI  - UPJ Obstruction in the Adult Population: Are Crossing Vessels Significant?
AB  - Ureteropelvic junction (UPJ) obstruction describes various causes of impaired
      drainage at the UPJ. Regardless of the cause, the end result is the same:
      impedance in the normal flow of urine from the renal pelvis into the proximal
      ureter, resulting in caliectasis and hydronephrosis. This may lead to progressive
      deterioration of renal function and, thus, often requires intervention to relieve
      the obstruction and restore the normal flow of urine. Defining the pertinent
      anatomy, the degree of obstruction, and differential renal function is key to
      determining whether and when intervention is necessary.

PMID- 16985692
TI  - Letter from the editors of reviews in urology.

PMID- 16985691
TI  - Modern brachytherapy for localized prostate cancers: the northwest hospital
      (Seattle) experience.
AB  - Modern ultrasound-guided prostate brachytherapy is rapidly changing the way
      localized prostate cancer is managed. With routine use of prostate-specific
      antigen screening, prostate cancer is being diagnosed in younger men, who are
      understandably concerned about the morbidity of radical treatments that may
      significantly decrease their quality of life. Numerous studies of prostate
      brachytherapy have shown the excellent disease control rates achieved while
      maintaining low levels of urinary and erectile difficulties. This report examines
      a modern implant method of brachytherapy; describes patient selection for
      brachytherapy, alone and in combination with external beam therapy; and presents
      results from a series of men followed for 12 years.

PMID- 16985693
TI  - Hand-assisted laparoscopy in urology.
AB  - Hand-assisted laparoscopy (HAL) allows surgeons direct hand contact with the
      operative field, maximizing tactile feedback and minimizing surgical injury to
      the patient. Indications for HAL include radical, donor, and partial
      nephrectomies, nephroureterectomy, and, most recently, dismembered pyeloplasties.
      The advantages of HAL surgical techniques in comparative experience with standard
      laparoscopic technique are described.

PMID- 16985694
TI  - Evaluation and treatment of men with biochemical prostate-specific antigen
      recurrence following definitive therapy for clinically localized prostate cancer.
AB  - Early detection and monitoring by serum prostate-specific antigen (PSA)
      measurement has increased the number of men presenting with potentially curable
      prostate cancer. Most will choose radical prostatectomy or some form of radiation
      therapy for treatment, but some will have evidence of biochemical disease
      recurrence following therapy, shown by a rising PSA level without other clinical
      evidence of disease. Radical prostatectomy involves the removal of all prostate
      tissue, causing the serum PSA to decline to undetectable levels within four to
      six weeks following surgery; a subsequent rise in the serum PSA to a detectable
      level indicates disease recurrence. Patients should be evaluated to assess
      whether rising PSA levels indicate local recurrence or early metastatic disease.
      The advantages of salvage radiation, endocrine therapy, and other treatment
      modalities in local disease recurrence must be weighed against potential side
      effects and the resulting decrease in quality of life. Radiation therapy does not
      immediately eradicate all PSA-producing cells; therefore the persistence of a
      detectable PSA does not necessarily imply residual cancer, but rising PSA levels
      indicate treatment failure. Salvage surgery can be performed after radiotherapy
      for the purpose of removing all viable cancer cells, but should be weighed
      against a higher incidence of surgical complications; cryoablation offers a less
      invasive therapeutic modality.

PMID- 16985696
TI  - Special Report on Prostatitis: State of the Art: Highlights of the Third Annual
      International Prostatitis Collaborative Network Meeting October 23-25, 2000,
      Washington, DC.

PMID- 16985695
TI  - Bladder cancer 2000: molecular markers for the diagnosis of transitional cell
      carcinoma.
AB  - The search continues for better tumor markers to improve the rate of detection of
      transitional cell carcinoma (TCC) more quickly in larger populations and to
      predict the possibility of disease recurrence. Among several new tests currently
      being screened, telomerase and hyaluronic acid/hyaluronidase (HA/HAase) have
      shown sensitivity and specificity equal to or better than cytology, and other
      promising tumor markers are being investigated. Although no marker has yet
      replaced the need to perform cystoscopy and cytology, the new tests can minimize
      the cost and difficulty of screening and long-term surveillance of patients who
      have or are at risk for bladder cancer.

PMID- 16985697
TI  - Urology in the desert 2000: highlights from the 76th annual meeting of the
      Western section american urological association.

PMID- 16985698
TI  - Prostate adenocarcinoma presenting as a large supraclavicular mass.
AB  - Metastatic prostate cancer is classically associated with bony or pelvic
      lymphatic metastasis. This case review represents an unusual case of prostate
      cancer presenting with a large left supraclavicular neck mass.

PMID- 16985699
TI  - Is nighttime voiding normal or anomalous?

PMID- 16985700
TI  - Cyclooxygenase-2 as a marker for prostate cancer.

PMID- 16985701
TI  - Paternity and hormone levels.

PMID- 16985702
TI  - Readership survey: reviews in urology.

PMID- 16985703
TI  - The effect of erectile dysfunction on quality of life following treatment for
      localized prostate cancer.
AB  - All forms of prostate cancer therapy carry significant risk of erectile
      dysfunction, but patients value sexual function so highly that they are often
      willing to choose a therapy that offers a shorter life expectancy but better
      potency following treatment. Advances in research methodology now allow reliable
      collection of meaningful data regarding patients' health-related quality of life,
      including both objective evaluation of patients' functional status and their
      perceptions of their own health and its impact on their existence. In the past
      decade, several validated and reliable questionnaires have been developed that
      are specifically designed to measure HRQOL in men with prostate cancer. Studies
      using these instruments have found that function and perceived bother may not be
      correlated; patients may express satisfaction with their therapy despite loss of
      sexual function. Erectile aids, including sildenafil, can be helpful for patients
      following treatment for localized prostate cancer.

PMID- 16985706
TI  - Focus on lower urinary tract symptoms: nomenclature, diagnosis, and treatment
      options: highlights from the 5th international consultation on benign prostatic
      hyperplasia june 25-27, 2000, paris, france.

PMID- 16985705
TI  - Saw Palmetto Berry as a Treatment for BPH.
AB  - Phytotherapeutic agents are often prescribed in Europe for the treatment of
      benign prostatic hyperplasia with lower urinary tract symptoms and are commonly
      used in the United States in over-the-counter preparations. Saw palmetto berry is
      the most popular of these agents, and in vitro some studies suggest that
      liposterolic extract of the plant has antiandrogenic effects that inhibit the
      type 1 and type 2 isoenzymes of 5alpha-reductase; however there are no clinical
      studies that show any decrease in serum dihydrotestosterone or prostate-specific
      antigen. Its efficacy in the treatment of lower urinary tract symptoms has not
      been conclusively proven. Clinical efficacy was suggested by a meta-analysis of
      Permixon, a formulation of saw palmetto, but the meta-analysis was done on
      suboptimal studies. One trial supports the equivalency of Permixon to finasteride
      in treating moderate to severe symptoms of benign prostatic hyperplasia, with
      less decrease in sexual function. However, without a control/placebo arm, the
      actual efficacy of the agents cannot be determined. Other than occasional
      gastrointestinal upset, no other side effects have been reported.

PMID- 16985707
TI  - Interstitial Cystitis and Bladder Research: Progress and Future Directions:
      Highlights of the National Institute of Diabetes and Digestive and Kidney
      Diseases (NIDDK) and the Interstitial Cystitis Association (ICA) International
      Research Symposium October 19-20, 2000, Minneapolis, MN.

PMID- 16985708
TI  - Dyspareunia: an unusual presentation of leiomyoma of the bladder.
AB  - Leiomyoma is a rare, benign tumor of the bladder. It frequently has an unusual
      presentation and its treatment options remain controversial. We describe a case
      of a leiomyoma of the bladder in a young female whose chief complaint was
      dyspareunia, and we review the management options.

PMID- 16985704
TI  - Current management of adolescent varicocele.
AB  - The finding of varicocele in an adolescent male is common. Varicocele rarely
      causes symptoms and is often diagnosed on the routine physical examination. There
      is clear association between varicocele and male factor infertility; however,
      there is debate about whether, when, and whom to treat when present in adult or
      adolescent males. This review of the epidemiology, etiology, pathophysiology, and
      treatment of the adolescent with varicocele will provide the reader with tools to
      make appropriate decisions in dealing with this condition.

PMID- 16985709
TI  - The y chromosome and infertility.

PMID- 16985710
TI  - Antibiotic therapy for interstitial cystitis?

PMID- 16985711
TI  - Comparison of Incontinence Risk after Radical Prostatectomy versus Hysterectomy.

PMID- 16985712
TI  - Determining the optimal treatment for advanced bladder cancer.

PMID- 16985713
TI  - Rethinking staging and treatment for renal cell cancer.

PMID- 16985715
TI  - Update on vesicoureteral reflux: pathogenesis, nephropathy, and management.
AB  - Clinical reflux was first visualized over 100 years ago. In the 1950s and early
      1960s, the assumption was that surgery to relieve bladder neck obstruction would
      have a positive effect on bladder function and reflux. By the early 1970s it was
      understood that the underlying structural problems leading to primary reflux were
      congenitally abnormal distal ureters and orifices. Researchers in the 1960s and
      1970s demonstrated the connection between reflux and renal scarring. More
      recently, reflux nephropathy in the absence of urinary tract infections has been
      observed, leading researchers to investigate an association between bladder
      dysfunction and reflux with resulting nephropathy. The cornerstone of management
      of the child with vesicoureteral reflux is antibiotic prophylaxis; treatment
      regimens for various grades of reflux are reviewed. Indications for surgical
      treatment of reflux are also discussed. Controversies regarding vesicoureteral
      reflux, including duration of prophylactic treatment, remain to be resolved.

PMID- 16985714
TI  - Current Clinical Applications of the In-capromab Pendetide Scan (ProstaScint(R)
      Scan, Cyt-356).
AB  - Prostate-specific antigen (PSA) has been extremely helpful in the detection of
      new or recurrent prostate cancer. However, localization of the recurrent tumor
      has been challenging with currently available radiographic modalities. The
      (111)In-capromab pendetide scan was developed to diagnose accurately and, more
      importantly, localize and stage a new or recurrent prostate cancer. Studies
      suggest that the (111)In-capromab pendetide scan can provide more accurate
      staging of clinically localized prostate cancer prior to staging lymphadenectomy
      or definitive therapy. It can also provide valuable information when local
      adjuvant radiation therapy is considered in men with biochemical cancer
      recurrence following radical prostatectomy.

PMID- 16985716
TI  - Prostate cancer gene therapy-what have we learned and where are we going?
AB  - With recent advances in genetic engineering, tumor biology, and immunology, gene
      therapy has been recognized as a promising new treatment option for various
      cancers, including prostate cancer. Several clinical trials of prostate cancer
      gene therapy, using therapeutic genes which include suicide genes,
      immunomodulatory genes, tumor suppressor genes, and anti-oncogenes, are under way
      and preliminary reports have emerged. Although gene therapy for prostate cancer
      is still at an early stage and requires additional technological breakthroughs,
      new insights obtained from recent clinical trials indicate a promising potential
      for prostate cancer gene therapy. In this report, general concepts, current
      progress, and future prospects in prostate cancer gene therapy are summarized.

PMID- 16985717
TI  - The epidemiology of acute urinary retention in benign prostatic hyperplasia.
AB  - One of the most important events in the natural history of BPH is acute urinary
      retention (AUR). Better estimates of AUR incidence are now available from both
      population-based studies and placebo control groups (patients diagnosed with
      BPH). Several strong risk factors for AUR have been identified by analytical
      epidemiology, the most important being serum PSA levels. When counseling patients
      with BPH who are considering watchful waiting, clinicians should also take into
      account prostate volume, maximum flow rate, and symptom severity.

PMID- 16985718
TI  - Best of the 2001 AUA Annual Meeting: Highlights of the 2001 Annual Meeting of the
      American Urological Association June 2-7, 2001, Anaheim, CA.

PMID- 16985719
TI  - Obstructive uropathy secondary to ureteroinguinal herniation.
AB  - Herniation of the ureter occurs infrequently in a sliding inguinal hernia.
      Massive herniation may cause ureteral obstruction leading to hydronephrosis.
      Computed tomography can demonstrate both ureteral herniation and associated
      hydronephrosis.

PMID- 16985720
TI  - A comparison of anticholinergic therapies in the treatment of overactive bladder.

PMID- 16985722
TI  - Men Undergoing ICSI: Y We Do What We Do.

PMID- 16985721
TI  - Biomarkers for early detection and optimized treatment for transitional cell
      carcinoma.

PMID- 16985723
TI  - Innovative Strategies Proposed at the Western AUA Meeting: Highlights From the
      Annual Meeting of the Western Section of the American Urological Association
      September 26-30, 1999, Monterey, California.

PMID- 16985724
TI  - A Gathering of Urologists and Urogynecologists: Highlights from the 29th Annual
      Meeting of the International Continence Society, the 2nd Annual Meeting of the
      International Children's Continence Society, and the 24th Annual Meeting of the
      International Urogynecology Association August 23-26, 1999, Denver.

PMID- 16985725
TI  - A new era in prostatitis research begins.

PMID- 16985726
TI  - Flexible Nephroscopy, Diagnostic Ureteroscopy for Upper Tract TCC, and
      Laparoscopic Cryoablation of Renal Tumors.

PMID- 16985727
TI  - Therapeutic strategies, predicting outcomes in patients with renal cell and
      transitional cell carcinomas.

PMID- 16985728
TI  - PSA Progression Postprostatectomy.

PMID- 16985730
TI  - What is the best way to treat incontinence: behavioral or drug treatment?

PMID- 16985729
TI  - Prenatal hydronephrosis-are voiding cystourethrograms necessary?

PMID- 16985731
TI  - Immunotherapy and peripheral-blood transplant for metastatic renal cell
      carcinoma.

PMID- 16985732
TI  - Growth factors and gene therapy for erectile dysfunction.

PMID- 16985733
TI  - Hereditary and familial prostate cancer: biologic aggressiveness and recurrence.

PMID- 16985734
TI  - Hyperprolactinemia and erectile dysfunction.
AB  - Hyperprolactinemia from a pituitary adenoma is a rare cause of erectile
      dysfunction. Men with erectile dysfunction who are found to have a low
      testosterone level should have a measurement of their prolactin level. Treatment
      consists of lowering the prolactin level by medication or surgery, or both.
      Bromocriptine, a dopamine agonist, is efficacious in lowering elevated prolactin
      levels and can simultaneously shrink these pituitary tumors. With large tumors,
      transphenoidal surgery may be used to debulk/remove the tumor. Post-treatment
      prolactin levels can be used to monitor the efficacy of treatment.

PMID- 16985735
TI  - Sacral nerve stimulation for the management of voiding dysfunction.
AB  - Voiding dysfunction is common, and patients with urge incontinence,
      frequency/urgency syndromes, and chronic urinary retention are challenging to
      treat once conservative therapies (such as pharmacologic agents, pelvic floor
      rehabilitation, and intermittent catheterization) have been exhausted. Sacral
      nerve stimulation (SNS) is a new, minimally invasive, reversible therapy for the
      management of refractory voiding dysfunction and provides an attractive
      therapeutic alternative for patients with this condition. In this review, the
      role of SNS in the management of voiding dysfunction is examined critically, and
      the efficacy, risks, and benefits of this new modality are evaluated.

PMID- 16985736
TI  - Immune and genetic therapies for advanced renal cell carcinoma.
AB  - Although we have witnessed advances in many aspects of cancer research and
      therapy in recent years, the ability to cure the majority of patients with
      advanced renal cell carcinoma (RCC) remains elusive. At the same time, it has
      become increasingly apparent that a better understanding of the genetic
      alterations and immune dysregulations in RCC will play a key role in finding a
      treatment. Therefore, clinical trials directed at specific genetic alterations
      and studies exploiting components of the immune system are being conducted. These
      studies provide new hope for an improved outlook for patients presenting with
      advanced RCC. The future prospects of RCC therapy will be, without doubt, built
      on the foundation of current investigative efforts in gene and immune therapy.
      This article reviews the current role of immunotherapy and gene therapy in the
      management of metastatic RCC. Finally, current clinical trials focusing on gene
      and immune therapies are listed.

PMID- 16985737
TI  - Strategies for the Management of Exstrophy, Nonpalpable Testis, Hydronephrosis:
      Highlights From the Annual Meeting of the American Academy of Pediatrics Section
      on Urology October 9-12, 1999, Washington, DC.

PMID- 16985738
TI  - New Techniques and Tools at the Endourology Congress: Highlights from the 17th
      World Congress on Endourology and SWL and 15th Basic Research Symposium September
      2-5, 1999, Rhodes, Greece.

PMID- 16985739
TI  - Spotlight on Bladder and Prostate Cancer and Urinary Retention at Glasgow
      Gathering: Highlights from the BAUS Annual Meeting June 21-25, 1999, Glasgow,
      Scotland.

PMID- 16985740
TI  - Gene therapy for prostate cancer.

PMID- 16985741
TI  - The significance of perineural invasion found on needle biopsy of the prostate:
      implications for definitive therapy.

PMID- 16985742
TI  - Adjuvant hormonal therapy in men with node-positive prostate cancer.

PMID- 16985743
TI  - Ureteropelvic Junction Obstruction: Endoluminal Ultrasound vs CT Angiography to
      Identify Crossing Vessels.

PMID- 16985744
TI  - CT After Nephrostolithotomy and Endoscopic Resection of TCC.

PMID- 16985745
TI  - Should I do a pubovaginal sling operation on an obese woman?

PMID- 16985746
TI  - Prostate size: does it matter?

PMID- 16985747
TI  - Premature ejaculation: prevalent but poorly understood.

PMID- 16985748
TI  - Primary aldosteronism caused by unilateral adrenal hyperplasia.
AB  - In the hypertensive population, primary aldosteronism has been reported to have a
      prevalence of 0.1% to 2%, with the main causes being aldosterone-producing
      adenomas and bilateral hyperplasia. However, there is a third rare entity, called
      unilateral adrenal hyperplasia, that contributes to primary aldosteronism.
      Unilateral hyperplasia and primary aldosteronism are the subjects of this case
      review.

PMID- 16985749
TI  - Minimally invasive procedures and medical management-their relative merits in
      treating lower urinary tract symptoms of benign prostatic hyperplasia.
AB  - Evidence is reviewed supporting the safety and efficacy of minimally invasive
      transurethral microwave thermotherapy and medical management in patients with
      benign prostatic hyperplasia. Recent data indicate more pronounced long-term
      beneficial effects of microwave treatment. alpha-Blockade, however, offers more
      rapid onset of action than does microwave treatment. Neoadjuvant and adjuvant
      alpha-blocker therapy can accelerate symptom and flow rate improvement in
      patients undergoing microwave treatment. Compared with medical management,
      microwave treatment also appears to possess greater versatility, allowing
      patients who fall within a broad range of baseline symptom severities and
      prostate sizes to be treated with a high probability of success.

PMID- 16985750
TI  - Ureteroscopic management of upper urinary tract urothelial malignancies.
AB  - The endoscope has made the transition from diagnostic tool to therapeutic aid in
      the upper urinary tract in recent years. Because of success using the
      ureteropyeloscope in the treatment of patients with upper tract stones and
      strictures, investigators are now looking at endoscopic management of urothelial
      malignancies above the bladder.

PMID- 16985752
TI  - Advances in genitourinary surgery: highlights from the 114th meeting of the
      american association of genitourinary surgeons april 5-8, 2000, san antonio, tex.

PMID- 16985754
TI  - New urologic strategies explored at jackson hole: highlights from the 20th annual
      jackson hole urologic conference january 22-28, 2000, jackson hole, wyo.

PMID- 16985753
TI  - Update on fetal surgery: highlights from the society for pediatric urology 49th
      annual meeting april 29, 2000, atlanta.

PMID- 16985751
TI  - Relationship between testosterone and erectile dysfunction.
AB  - Although erectile function is clearly androgen dependent, is it just as clear at
      what level of testosterone erectile dysfunction (ED) begins? Does the decline in
      testosterone that occurs with aging always produce ED? Are exogenous androgens
      the answer to ED? The answers range from clear to complex.

PMID- 16985755
TI  - Tumor markers: an update on human kallikrein 2.

PMID- 16985756
TI  - Vaccine-based immunotherapy for prostate cancer.

PMID- 16985757
TI  - Diagnostic index and dysfunction treatment.

PMID- 16985758
TI  - First-line therapy for stress incontinence.

PMID- 16985759
TI  - Fibrous inflammatory pseudotumor of the bladder.
AB  - Fibrous pseudotumor of the bladder, a rare, benign, and proliferative lesion of
      the submucosal stroma, can be mistaken on gross examination for a malignant
      lesion and must be differentiated on histologic examination from several bladder
      malignancies. Radiographic examination alone cannot establish a definitive
      diagnosis. Complete transurethral resection of such lesions appears to be
      curative.

PMID- 16985761
TI  - Internet information on urology.
AB  - Keeping up with all the current information in the field of urology is not as
      difficult anymore, with the many sources available on the World Wide Web. But
      which sites will give you the most and best data? Where can you go for continuing
      medical education? For sources of patient education information? For a list of
      upcoming meetings? Check below for recommendations on general medical, urology
      specific, and reference resources.

PMID- 16985760
TI  - Transcatheter therapeutic embolization of genitourinary pathology.
AB  - With the advent of smaller vascular catheters and improved imaging techniques,
      percutaneous transcatheter embolization has become a valuable adjunct for the
      treatment of patients with various genitourinary pathologic conditions. Multiple
      embolic agents are now employed in an array of situations to devascularize
      organs, stop bleeding, and occlude passageways.

PMID- 16985762
TI  - Best of the 2000 AUA Annual Meeting: Highlights from the 95th American Urological
      Association Annual Meeting April 29-May 4, 2000, Atlanta.

PMID- 16985763
TI  - Surgical, Pharmacological, and Technological Advances: Highlights from the NYU
      Post-Graduate Medical School Course December 9-11, 1999, New York.

PMID- 16985764
TI  - Focus on sexual dysfunction, tissue engineering, gene therapy: highlights from
      the first fall meeting of the society for the study of impotence october 1-3,
      1999, Boston.

PMID- 16985765
TI  - Special report on prostatitis initiatives and future research: highlights of the
      second international prostatitis collaborative network meeting november 3-5,
      1999, bethesda, MD.

PMID- 16985766
TI  - Diagnosis of interstitial cystitis: another look.

PMID- 16985767
TI  - Improving the Safety of TURP.

PMID- 16985768
TI  - Molecular markers for renal cell carcinoma.

PMID- 16985769
TI  - Cryptorchidism and overactive bladder.

PMID- 16985770
TI  - Stress urinary incontinence.

PMID- 16985771
TI  - Abdominal pain associated with an intra-abdominal gonad in an adult.
AB  - Controversy still surrounds management of cryptorchidism in adults. Options
      include orchiectomy, orchiopexy, and close observation. What about fertility if
      orchiectomy is chosen? How is the risk of cancer affected when observation is the
      choice? Follow the reasoning for the management strategy for this adult
      presenting with abdominal pain.

PMID- 16985772
TI  - Selecting candidates for radical prostatectomy.
AB  - Men with clinically localized prostate cancer and their physicians are faced with
      the management decision of radical prostatectomy, radiation therapy, or watchful
      waiting. Who is the best candidate for radical prostatectomy? Is cure the only
      relevant outcomes parameter? Does age make a difference? Are imaging studies
      necessary? This review provides answers, step-by-step, in the decision-making
      process.

PMID- 16985773
TI  - Seminal vesicle invasion by prostate cancer: prognostic significance and
      therapeutic implications.
AB  - When the pathologist's report following radical prostatectomy describes seminal
      vesicle invasion (SVI), generally the outlook for the patient is poor. But are we
      all on the same page of the same book when we talk about SVI? Does it mean
      muscular wall invasion? Does it include the ejaculatory duct? Getting a clear
      definition can have far-reaching clinical implications for patient prognosis and
      treatment.

PMID- 16985774
TI  - LUTS, BPH, BPE, BPO: A Plea for the Logical Use of Correct Terms.

PMID- 16985775
TI  - Surgical, Pharmacological, and Technological Advances in Adult and Pediatric
      Urology: Highlights from the NYU Post-Graduate Medical School course December 10
      12, 1998 New York, NY.

PMID- 16985776
TI  - Stone-Forming Bacteria, Laser Lithotripsy, and Telesurgery Featured at World
      Congress: Highlights from 16th World Congress on Endourology & Shock Wave
      Lithotripsy (SWL) September 3-6, 1998, New York, NY.

PMID- 16985777
TI  - Prostate Cancer Markers and Treatments Ranging From Gene Therapy to Cryosurgery
      Examined at AUA: Highlights from the American Urological Association 93rd Annual
      Meeting May 30-June 4, 1998, San Diego, Calif.

PMID- 16985778
TI  - Caught up in uroweb.
AB  - Emphasizing "interactive exchange and discussion" among urologists worlwide, the
      mission of Uroweb (www.uroweb.org) is to be a global resource for urologic
      specialists and investigators, although the content is mostly from urologists in
      Europe and the United States. The European Association of Urology, which
      developed this World Wide Web site, notes it was born out of the desire to link
      educational and practical treatment information from a wide variety of sources.

PMID- 16985779
TI  - Early clinical experience with monti procedure and managing the nonpalpable
      testis in children.

PMID- 16985780
TI  - Urinary incontinence after radical retropubic prostatectomy.

PMID- 16985781
TI  - Synchronous RCC and TCC of the Kidney in a Patient With Multiple Recurrent
      Bladder Tumors.
AB  - Development of concomitant renal TCC and RCC is an uncommon occurrence, yet many
      interesting issues can be addressed with this model. The possibility of
      misdiagnosing a renal TCC for an RCC, the options and importance of treating a
      retained ureteral stump after performing a radical nephrectomy for a renal TCC,
      and the risk of developing lower tract TCC in patients with upper tract TCC are
      some of the issues raised in this case review.

PMID- 16985782
TI  - Telemedicine and surgical robotics: urologic applications.
AB  - Medical treatment can be improved through integration and application of advances
      in technology, computers, and engineering. Accuracy and reliability are essential
      characteristics of any mechanical system, and with the evolution of machines
      capable of precise movements, the integration of medicine and machine is
      achievable. Early mechanical devices were effective in performing simple,
      repetitive tasks but were not sophisticated enough for independent function. In
      the automobile industry, robots could work on the assembly line executing these
      cyclic tasks. These machines could execute simple, reiterative movements without
      integrating new information from the environment. In this day and age, robots
      have evolved into sophisticated mechanical devices that can "react" to data
      detected in the environment to determine the next course of events. They have
      evolved from the assembly line to the operating room, assisting surgeons during
      surgery to participating in remote telesurgical procedures.

PMID- 16985783
TI  - Medical and minimally invasive treatment of urinary incontinence.
AB  - Newer agents and procedures give urologists more options in treating patients who
      have urinary incontinence related to such etiologies as an ineffective sphincter,
      detrusor hypersensitivity, obstruction, or a combination of these. Abolition of
      the involuntary contractions characteristic of detrusor instability can be
      accomplished pharmacologically or surgically. First-line anticholinergic agents
      are tolterodine and oxybutynin XL, given orally. Alternatively, intravesical
      administration provides a high concentration of drug, such as capsaicin or
      resiniferatoxin, at the detrusor muscle level. However, this commits the patient
      to intermittent self-catheterization. Surgery is reserved for those who have
      failed prolonged trials of conservative therapies. For patients with intractable
      urge incontinence, urologists have the new technique of sacral nerve stimulation.

PMID- 16985785
TI  - Mapping the future for incontinence treatment worldwide: highlights from the
      first international consultation on incontinence june 28-july 1, 1998, monaco.

PMID- 16985784
TI  - Best of the 1999 AUA Annual Meeting: Highlights from the American Urological
      Association Annual Meeting May 1-6, 1999, Dallas, Texas.

PMID- 16985787
TI  - Managing incontinence: the tip of the iceberg.

PMID- 16985786
TI  - Pediatric problems-from hydronephrosis to enuresis-discussed at AAP meeting:
      highlights from the american academy of pediatrics section on urology, october 17
      19, 1998, san francisco, calif.

PMID- 16985788
TI  - American academy of pediatrics policy statements on circumcision and urinary
      tract infection.

PMID- 16985789
TI  - Sexual function and benign prostatic hyperplasia.

PMID- 16985790
TI  - Perplexing problem of persistently painful prostatitis.
AB  - Chronic prostatitis has been a perplexing problem for urologists for decades.
      This review explores the perils and pitfalls urologists encounter with
      epidemiology, etiology, classification, diagnosis, and treatment of this
      syndrome. The major question involves the problem of developing rational
      treatment plans for patients with a medical condition associated with
      genitourinary pain, variable voiding, and sexual dysfunction but no obvious and
      accepted etiology. Exciting, innovative, ongoing research does offer some
      solutions and management strategies that urologists can even now incorporate into
      their practice while waiting for the fundamental questions to be answered.

PMID- 16985791
TI  - Laser prostatectomy: checkup on the promises.
AB  - Voiding symptoms caused by benign prostatic hyperplasia are responsible for
      significant compromise in the quality of life of many men. As our population
      ages, more men are seeking medical evaluation and treatment for this condition.
      In addition, with the recognition that this benign condition rarely creates
      significant life-threatening medical problems, there has been a movement toward
      less invasive therapies that are associated with the least possible iatrogenic
      morbidity. Among the currently available, minimally invasive techniques is laser
      prostatectomy. Is it standing up to its rival, transurethral resection of the
      prostate, or lagging behind?

PMID- 16985792
TI  - BPH Plus Prostate Cancer Therapy and Markers Featured at EAU: Highlights from the
      14th Annual Congress of the European Association of Urology April 7-10, 1999,
      Stockholm, Sweden.

PMID- 16985793
TI  - Stones, BPH, Renal and Prostate Disease Discussed at Jackson Hole: Highlights
      from the 19th Annual Jackson Hole Urologic Conference January 23-30, Jackson
      Hole, Wyo.

PMID- 16985794
TI  - New Strategies for Bladder and Prostate Cancer, BPH Explored by South Central
      Urologists: Highlights from the South Central Section of the American Urological
      Association January 16-20, 1999, Cancun, Mexico.

PMID- 16985795
TI  - Pediatric Percutaneous Nephrolithotomy and CT vs IVP for Flank Pain Diagnosis.

PMID- 16985796
TI  - Prevalence of sexual dysfunction, efficacy of therapy.

PMID- 16985797
TI  - Managing stress incontinence and classifying detrusor instability.

PMID- 16985798
TI  - Prostate biopsy schemes and the detection of prostate cancer.

PMID- 16985799
TI  - Thyroid autoantibodies, telomerase activity, vascular endothelial growth factor,
      and bone scanning.

PMID- 16985800
TI  - Nephron-sparing surgery for renal cell carcinoma.
AB  - Nephron-sparing surgery has become an established surgical treatment for patients
      with renal cell carcinoma (RCC), particularly in situations in which preservation
      of renal parenchyma is critical. However, due to the fear of local renal fossa
      recurrence with nephron-sparing surgery, radical nephrectomy has historically
      been the treatment of choice for patients with unilateral RCC and a normal
      contralateral kidney. Recently, increased incidence of low-stage, localized,
      solitary RCC has led to renewed interest in partial nephrectomy. With excellent
      disease-specific survival and recurrence rates comparable to that achieved with
      radical nephrectomy, nephron-sparing surgery can be confidently utilized in
      treating patients with stage T1 RCC lesions (<7 cm) and a normal contralateral
      kidney. The utility of nephron-sparing surgery in the context of adjunctive
      systemic immunotherapy remains to be explored.

PMID- 16985801
TI  - Validity of the "bother score" in the evaluation and treatment of symptomatic
      benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a condition that is common among older men.
      It causes a variety of clinically significant lower urinary tract signs and
      symptoms. BPH is rarely life-threatening; the decision to seek treatment is
      frequently based on the degree to which patients find the symptoms bothersome and
      disruptive of daily activities. Recently developed reliable and valid outcome
      measures to evaluate treatments for BPH are clinical tools that urologists can
      use to determine the extent of bother and make treatment decisions. A single
      question used to determine the "bother score" provides a widely used and
      statistically valid measure of the need for treatment of BPH. Validation data
      support the argument that the bother score is a statistically reliable measure of
      treatment outcome in patients with BPH who view their symptoms as bothersome.

PMID- 16985802
TI  - Practical management of recurrent urinary tract infections in premenopausal
      women.
AB  - Recurrent urinary tract infections (UTIs) are a major healthcare concern for
      premenopausal, healthy, sexually active women. A practical approach to the
      management and prevention of recurrent UTIs should be simple, practical, and cost
      effective. Low-dose or postcoital antimicrobial therapy can be effective for
      women with constellations of many recurrent UTIs, but for women with 2 to 4 UTIs
      per year, the most cost-effective and empowering management strategy is patient
      initiated antimicrobial treatment.

PMID- 16985803
TI  - What's New in Prostate Cancer, Benign Prostatic Hyperplasia, and Minimally
      Invasive Surgery?: Highlights from the XIXth Congress of the European Association
      of Urology, March 23-27, 2004, Vienna, Austria.

PMID- 16985804
TI  - Prostate cancer update: 2004: highlights from the 4th international prostate
      cancer congress, grand bahama island, bahamas, july 15-18, 2004.

PMID- 16985805
TI  - Optimal surgical management of the obese man with prostate cancer: laparoscopic
      or perineal radical prostatectomy.

PMID- 16985806
TI  - Radical perineal prostatectomy: a more optimal treatment approach than
      laparoscopic radical prostatectomy in obese patients?
AB  - In comparison with laparoscopic radical prostatectomy (LRP), the perineal
      approach to radical prostatectomy offers specific technical advantages related to
      obesity and its unique surgical challenges. Radical perineal prostatectomy (RPP)
      reduces operative time and its associated risk of complication, which may be more
      pronounced in obese men. It allows for low blood loss, low postoperative use of
      narcotics for pain, short hospital stays, and requires only 1 small perineal
      incision. With a proven history of success, RPP presents obese men with an
      advantageous surgical option.

PMID- 16985807
TI  - Laparoscopic radical prostatectomy in obese patients: feasible or foolhardy?
AB  - More than 70% of men who are candidates for radical prostatectomy can be
      classified as either overweight or obese by body mass index. The role for
      laparoscopic radical prostatectomy (LRP) in treating these patients remains to be
      defined. A wealth of experience from bariatric surgery confirms that laparoscopic
      procedures can be performed successfully, even in the setting of morbid obesity,
      despite well-defined derangements in respiratory dynamics. Using the technical
      modifications outlined here, LRP can be performed safely and effectively in obese
      patients. Obesity raises the degree of difficulty for LRP, however, resulting in
      longer operative times and possibly a higher rate of open conversion. For this
      reason, surgeons early in their LRP experience are advised to avoid obese
      patients until they have become facile in the performance of LRP in normal-weight
      individuals.

PMID- 16985808
TI  - Twenty-six-year-old primigravid woman with a cystic mass.

PMID- 16985809
TI  - Early detection of prostate cancer.

PMID- 16985810
TI  - Effect of testis biopsy on testosterone production.

PMID- 16985811
TI  - Antibiotics and alpha-Blockers for Chronic Prostatitis: Evidence From Recent
      Randomized Placebo-Controlled Studies.

PMID- 16985812
TI  - Adjunctive therapy to promote stone passage.
AB  - The majority of individuals with nephrolithiasis have small ureteral stones that
      pass spontaneously. However, patients may experience severe pain during this
      process, which significantly alters their quality of life and may limit their
      vocational responsibilities. Therefore, measures to facilitate stone passage are
      uniformly embraced. We discuss methods to enhance spontaneous stone passage as
      well as the elimination of fragments generated with extracorporeal shock-wave
      lithotripsy.

PMID- 16985813
TI  - Anomalies of the wolffian duct derivatives encountered at radical prostatectomy.
AB  - Abnormalities of wolffian duct derivatives are usually encountered in young
      subjects. We identified 4 instances of embryologic malformations of these
      structures in patients who underwent radical prostatectomy (RP). The first
      patient had unilateral renal agenesis and a seminal vesicle cyst identified
      preoperatively by computed tomography. The seminal vesicle cyst was removed
      during RP. The second patient had renal agenesis and an ectopic ureter entering
      the right seminal vesicle. These were treated with ureterectomy during RP. The
      third patient had unilateral duplication of the vas deferens of no clinical
      consequence. Finally, the fourth patient had left-sided absence of both the vas
      deferens and seminal vesicle. The anatomy of the lower pelvis is most accurately
      shown on magnetic resonance imaging. Lower urinary tract malformations are an
      uncommon occurrence in males. Surgeons who perform numerous RPs will, however,
      find additional urologic pathologies during RP that may require consideration and
      tailored management.

PMID- 16985814
TI  - Treatment of stress urinary incontinence with duloxetine hydrochloride.
AB  - Currently, there are no approved medications for the treatment of stress urinary
      incontinence (SUI) in the United States. The effectiveness of duloxetine in the
      treatment of SUI is linked to its inhibition of presynaptic neuronal reuptake of
      serotonin and norepinephrine in the central nervous system, resulting in elevated
      levels of serotonin and norepinephrine in the synaptic cleft. In animal studies,
      this agent leads to an increase in nerve stimulation to the urethral striated
      sphincter muscle. A similar mechanism in women is believed to result in stronger
      urethral contractions, with improved sphincter tone during urine storage and
      physical stress. In 3 randomized, placebo-controlled clinical trials, patients
      receiving duloxetine had a statistically significant and clinically relevant
      reduction in the number of incontinence episodes and a corresponding improvement
      in quality of life. If this use of duloxetine is approved by the U.S. Food and
      Drug Administration, as it has been by the European regulatory agencies, it will
      be the first drug indicated for the treatment of SUI. This pharmacologic therapy
      is an additional option for women and is likely to become an integral component
      of patient management.

PMID- 16985815
TI  - Long-term effects of testim(r) 1% testosterone gel in hypogonadal men.
AB  - A new transdermal preparation, Testim(R) 1% testosterone gel, has recently become
      available for normalization of serum testosterone in hypogonadal men. In short
      term studies, it has been shown to reverse the clinical signs and symptoms of low
      testosterone and to be well tolerated with less applicationsite irritation than
      with testosterone patches. In 2 long-term studies with Testim, the predose early
      morning serum testosterone (T), dihydrotestosterone (DHT), and free testosterone
      (FT) levels were assessed. Serum T, DHT, and FT were all maintained in the normal
      range for up to 12 months. In these studies, involving a total of 371 hypogonadal
      men, evaluation by means of dual-energy x-ray absorptiometry revealed a
      significant increase from baseline in bone mineral density. A significant
      improvement was also observed in body composition (increased lean body mass,
      decreased fat mass, and decreased percentage fat). In addition, significant
      improvements in mood and sexual function were maintained for up to 12 months of
      treatment. The parameters measured included sexual performance, sexual
      motivation, sexual desire, and occurrence of spontaneous erections. These data
      from the 2 long-term studies support the results of the 90-day studies with
      Testim showing that the gel significantly improves the signs and symptoms
      associated with low testosterone compared with placebo. The data also support the
      conclusion that these improvements are maintained for up to 1 year of additional
      treatment.

PMID- 16985816
TI  - Endourology: a basic science and clinical update: highlights from the 22nd world
      congress on endourology and shockwave lithotripsy/20th basic research symposium,
      november 2-5, 2004, mumbai, India.

PMID- 16985817
TI  - Updates in Pediatric Urology: Highlights of the American Academy of Pediatrics
      Section on Urology Annual Meeting, October 8-11, 2004, San Francisco, CA.

PMID- 16985818
TI  - Prostatic intraepithelial neoplasia in a 53-year-old man.

PMID- 16985819
TI  - Dawning of the age of chemotherapy for prostate cancer.

PMID- 16985821
TI  - Pain after suburethral sling procedures.

PMID- 16985820
TI  - Urinary acidity and pain in interstitial cystitis.

PMID- 16985822
TI  - Open versus laparoscopic radical prostatectomy.
AB  - Expert laparoscopic surgeons have demonstrated that laparoscopic radical
      prostatectomy with or without robotic assistance can be performed with excellent
      results. There is no evidence that laparoscopic radical prostatectomy with or
      without robotic assistance offers any clinically relevant advantage over open
      radical prostatectomy. Laparoscopic radical prostatectomy with or without robotic
      assistance requires a significant learning curve, is a longer surgical procedure,
      carries greater costs, and requires an expanded operating room team. The
      literature suggests that laparoscopic radical prostatectomy is associated with
      more intraoperative complications and higher positive surgical margins. The
      lesser amount of postoperative bleeding associated with laparoscopic radical
      prostatectomy is not clinically relevant. Laparoscopic radical prostatectomy is
      not associated with less pain and does not facilitate earlier urinary catheter
      removal. The best way to improve overall outcomes after radical prostatectomy is
      to direct patients to expert open or laparoscopic surgeons.

PMID- 16985823
TI  - The molecular basis of erectile dysfunction: from bench to bedside.
AB  - Erectile dysfunction is a common problem affecting many men across all age
      groups. Its etiology is multifactorial. Hormonal, vascular, neurogenic,
      lifestyle, and psychological entities have all been implicated as causative
      agents. The molecular basis underlying its etiology and progression is complex
      and still challenges researchers in the field. Nonetheless, newly discovered
      common pathways and targets of its pathogenesis have opened a new era for both
      prevention and active treatment of the disease. This review describes some of the
      known molecular mechanisms contributing to erectile dysfunction and discusses the
      future of gene therapy for the disease.

PMID- 16985824
TI  - Human Papillomavirus: Confronting the Epidemic-A Urologist's Perspective.
AB  - The human papillomavirus (HPV) has long been associated with the development of
      penile lesions-condyloma acuminatum and verrucous carcinoma of the penis. More
      recently, HPV has been implicated as an etiology of more serious neoplasias in
      men-penile carcinoma and other anogenital squamous-cell carcinomas. HPV is now
      widely recognized as responsible for more than 95% of cervical cancers in women.
      HPV seems to have been receiving relatively scant attention to date-from
      physicians in general, and particularly from urologists-as a venereal disease of
      significant concern. Yet HPV is recognized to be the most frequently acquired
      sexually transmitted viral infection worldwide. It is estimated that
      approximately 6 million new cases of HPV are sexually transmitted annually in the
      United States. Fortunately, many, if not most, of these HPV infections are
      transient. However, each newly acquired infection has the potential to persist as
      an incurable, lifelong affliction, generating a significant increase in the long
      term risk of cancer for patients and their sexual partners. Many of these HPV
      related cancers will not become manifest until decades later.

PMID- 16985826
TI  - Orgasmic Pain and a Detectable PSA Level after Radical Prostatectomy.

PMID- 16985825
TI  - Best of the 2005 AUA Annual Meeting: Highlights from the 2005 Annual Meeting of
      the American Urological Association, May 21-May 26, 2005, San Antonio, TX.

PMID- 16985827
TI  - Discussion of Last Issue's Case Scenario.

PMID- 16985828
TI  - Early hormonal therapy for prostate cancer: the good, the bad, and the ugly.

PMID- 16985829
TI  - Choosing earlier therapy for muscle-invasive bladder cancer.

PMID- 16985831
TI  - Dutasteride: a review of current data on a novel dual inhibitor of 5alpha
      reductase.
AB  - Dutasteride is used in the treatment of benign prostatic hyperplasia. Like
      finasteride, it reduces serum prostate-specific antigen levels by approximately
      50% at 6 months and total prostate volume by 25% in 2 years. It differs from
      finasteride in that it inhibits both isoenzymes of 5alpha reductase and results
      in near-complete suppression of serum dihydrotestosterone. Randomized placebo
      controlled trials over 2 years have shown the efficacy of dutasteride in
      symptomatic relief, improvements in quality of life and peak urinary flow rate,
      and reduction of acute urinary retention events and need for surgery. Side
      effects occurring in therapy with dutasteride are decreased libido, erectile
      dysfunction, ejaculation disorders, and gynecomastia. However, when dutasteride
      treatment is compared with placebo, these sexual adverse events are only modestly
      elevated. Long-term use over 4 years did not increase side effects. An efficient
      treatment of side effects is the combination of dutasteride and tamsulosin,
      especially for patients with large prostate volumes. Finally, the anticancer
      properties of dutasteride have been shown in placebo-controlled trials and are
      being investigated in the ongoing Reduction by Dutasteride of Prostate Cancer
      Events (REDUCE) trial.

PMID- 16985832
TI  - Three-Dimensional (3D) Vision: Does It Improve Laparoscopic Skills? An Assessment
      of a 3D Head-Mounted Visualization System.
AB  - Laparoscopic urologic procedures have become increasingly popular, but their
      widespread use has been limited by training issues. The use of 3-dimensional (3D)
      vision might aid in training and performance of laparoscopic tasks. The purpose
      of this study was to evaluate a 3D visual system used by novice laparoscopists.
      In this prospective, randomized study, 24 novice laparos-copists were evaluated
      on a validated and standardized laparoscopic task using both 2-dimensional (2D)
      and 3D visualization systems. The task was performed more rapidly with 3D
      visualization (108 vs. 127 seconds, P < .05). On subjective evaluations,
      participants believed the task was easier with the 3D system, and participants
      preferred the 3D system to the 2D system by a 2:1 margin. 3D visualization
      improves the learning curve for laparoscopic surgery. Surgeons should consider 3D
      systems when learning complex laparoscopic surgeries. Further evaluation of
      operative times and complications is needed in clinical studies.

PMID- 16985830
TI  - Adenoviral gene therapy, radiation, and prostate cancer.
AB  - Viral gene therapy has exceptional potential as a specifically tailored cancer
      treatment. However, enthusiasm for cancer gene therapy has varied over the years,
      partly owing to safety concerns after the death of a young volunteer in a
      clinical trial for a genetic disease. Since this singular tragedy, results from
      numerous clinical trials over the past 10 years have restored the excellent
      safety profile of adenoviral vectors. These vectors have been extensively studied
      in phase I and II trials as intraprostatically administered agents for patients
      with locally recurrent and high-risk local prostate cancer. Promising therapeutic
      responses have been reported in several studies with both oncolytic and suicide
      gene therapy strategies. The additional benefit of combining gene therapy with
      radiation therapy has also been realized; replicating adenoviruses inhibit DNA
      repair pathways, resulting in a synergistic sensitization to radiation. Other,
      nonreplicating suicide gene therapy strategies are also significantly enhanced
      with radiation. Combined radiation/gene therapy is currently being studied in
      phase I and II clinical trials and will likely be the first adenoviral gene
      therapy mechanism to become available to urologists in the clinic. Systemic gene
      therapy for metastatic disease is also a major goal of the field, and clinical
      trials are currently under way for hormone-resistant metastatic prostate cancer.
      Second- and third-generation "re-targeted" viral vectors, currently being
      developed in the laboratory, are likely to further improve these systemic trials.

PMID- 16985834
TI  - Best of the SIU Meeting on Prostatic Disease: Highlights from the Societe
      Internationale d'Urologie Meeting on Prostatic Disease: Recent Advances and New
      Technologies, September 29-October 1, 2005, Bariloche, Patagonia, Argentina.

PMID- 16985833
TI  - Use of laparoscopy in pediatric urology.
AB  - The goal of laparoscopy is to minimize patient morbidity while maintaining
      successful outcomes. The use of laparoscopy in urology has grown significantly
      over the past 30 years. Its use has been slower to gain acceptance in pediatrics
      than in the adult population. Laparoscopic orchidopexies and nephrectomies are
      commonly performed and have become widely accepted as alternatives to open
      surgery, if not the gold standard. The more technically demanding procedures,
      such as laparoscopic pyeloplasty, laparoscopic-assisted bladder reconstruction,
      and laparoscopic ureteral reimplantation, tend to be performed at selected
      centers and have yet to achieve widespread acceptance. As laparoscopy is applied
      more widely in pediatric urology, its potential benefits and drawbacks will be
      clarified.

PMID- 16985835
TI  - Carcinoid tumor of the kidney: case report and review of the literature.
AB  - Carcinoid tumors are low-grade malignant tumors that arise from neuroendocrine
      cells. Primary renal carcinoid tumors are extremely uncommon. They seem to be
      more indolent than renal cell carcinomas, although metastases to regional lymph
      nodes, liver, and bone have been described. The presence of metastases seems to
      indicate a more malignant course; however, even with metastases a patient might
      live for 3 or 4 years. Renal carcinoid tumors should be managed by radical or
      partial nephrectomy, and good outcomes have been obtained for organ-confined
      disease after radical excision. Conventional methods of imaging are inadequate
      for detecting smaller carcinoids, so somatostatin receptor scintigraphy should
      complement computed tomography and magnetic resonance imaging when searching for
      occult or metastatic disease. Close follow-up after surgery is necessary.

PMID- 16985836
TI  - The use of botulinum toxin in men with benign prostatic hyperplasia.

PMID- 16985837
TI  - Detecting Prostate Cancer with Molecular Markers: uPM3.

PMID- 16985838
TI  - Role of fibrin in the development of surgical adhesions.

PMID- 16985839
TI  - Orgasmic Pain and a Detectable PSA Level after Radical Prostatectomy.

PMID- 16985840
TI  - Chronic epididymitis: a practical approach to understanding and managing a
      difficult urologic enigma.
AB  - Many patients with unilateral or bilateral testicular, epididymal, or scrotal
      pain as their sole presenting symptom receive a diagnosis of "chronic
      epididymitis." This common clinical entity is diagnosed and treated by practicing
      urologists but essentially ignored by academic urologists. This article defines
      chronic epididymitis, reviews current knowledge regarding its etiology, and
      describes appropriate physical examination and clinical testing for patients with
      the condition. The recently developed Chronic Epididymitis Symptom Index is
      presented, which can be used for baseline evaluation and follow-up of patients
      with chronic epididymitis, both in clinical practice and in research treatment
      trials. Treatment options, from watchful waiting to medical therapy to
      epididymectomy, are reviewed.

PMID- 16985843
TI  - Advances in the Treatment of Genitourinary Cancer: Highlights from the 3rd Annual
      Meeting of the Society of Urologic Oncology, December 13-14, 2002, Washington,
      DC.

PMID- 16985842
TI  - Drug-induced urinary calculi.
AB  - Urinary calculi may be induced by a number of medications used to treat a variety
      of conditions. These medications may lead to metabolic abnormalities that
      facilitate the formation of stones. Drugs that induce metabolic calculi include
      loop diuretics; carbonic anhydrase inhibitors; and laxatives, when abused.
      Correcting the metabolic abnormality may eliminate or dramatically attenuate
      stone activity. Urinary calculi can also be induced by medications when the drugs
      crystallize and become the primary component of the stones. In this case, urinary
      supersaturation of the agent may promote formation of the calculi. Drugs that
      induce calculi via this process include magnesium trisilicate; ciprofloxacin;
      sulfa medications; triamterene; indinavir; and ephedrine, alone or in combination
      with guaifenesin. When this situation occurs, discontinuation of the medication
      is usually necessary.

PMID- 16985844
TI  - Advances in the Treatment of Pelvic Floor Dysfunction: Highlights from the 23rd
      Annual Scientific Meeting of the American Urogynecologic Society, October 17-19,
      2002, San Francisco, CA.

PMID- 16985841
TI  - Androgen replacement therapy in the aging male.
AB  - Beginning around age 40 years, men experience a decrease in testosterone level
      referred to as "andropause"-and the pathophysiologic changes that accompany this
      decrease. Androgen replacement therapy, typically used for the treatment of
      senile hypogonadism, is evolving as a potential treatment of various other
      conditions related to testosterone loss, such as osteoporosis, sarcopenia, and
      even psychological symptoms. As with any treatment modality, certain patient
      factors are more predictive of success with minimal adverse effects, and
      consideration must be given to concomitant conditions. This article will provide
      a review of recent studies examining the effects of androgen supplementation and
      evaluate the purported benefits and potential risks of this therapy. Further
      research is anticipated to elucidate the most appropriate candidates, as well as
      other potential indications, for this treatment.

PMID- 16985845
TI  - 3-month-old boy with a febrile urinary tract infection.

PMID- 16985846
TI  - Androgen replacement therapy: treatment advances and clinical implications.

PMID- 16985848
TI  - A New Quality-of-Life Scoring Instrument for Patients With Erectile Dysfunction.

PMID- 16985847
TI  - Expectant management of prostate cancer.

PMID- 16985849
TI  - Weighing cost versus efficacy in assisted reproductive technology.

PMID- 16985850
TI  - Overview of overactive bladder, prostatitis, and lower urinary tract symptoms for
      the primary care physician.
AB  - As an increasing number of treatment options for urologic disorders become
      available, patients with these conditions are more often able to be managed in
      the primary care setting. Primary care physicians, therefore, must become more
      knowledgeable of the proper urologic terminology and the screening tools that
      have traditionally been used by urologists. To that end, this article reviews the
      terminology associated with lower urinary tract symptoms and describes the
      evaluation and treatment of patients presenting with these symptoms. The
      diagnoses of overactive bladder and prostatitis are discussed, as well as the
      therapeutic options available for these patients.

PMID- 16985851
TI  - Differential diagnosis and treatment of impaired bladder emptying.
AB  - Although much attention is paid to urinary incontinence, the condition of
      incomplete bladder emptying is becoming more common with the aging of the US
      population and the widespread use of anticholinergic drugs to treat overactive
      bladder. This disorder can often be silent until end-stage presentation of
      overflow incontinence. In this article, we review the pathophysiologic conditions
      of the bladder and urethra that can cause impaired bladder emptying and discuss
      how to evaluate and screen the patient with a bladder that does not empty. In
      addition, we provide an overview of treatment options available for impaired
      bladder emptying and consider the research that is under way to find the best
      therapies for the failing bladder.

PMID- 16985853
TI  - Evaluation of voiding dysfunction and measurement of bladder volume.
AB  - When evaluating patients with voiding dysfunction, noninvasive tests such as
      uroflowmetry and measurement of postvoid residual urine volume (PVR) can help to
      determine whether additional testing is warranted. PVR can be measured by 2
      methods: catheterization or bedside bladder ultrasonography. Although both
      methods have advantages, the convenience, efficiency, and safety of bladder
      ultrasound makes its use beneficial in a wide variety of populations, including
      hospitalized patients, children, and the elderly. More recently, bladder
      ultrasound has been used for other procedures, such as suprapubic aspiration,
      evaluation of intravesical masses, and to determine bladder wall thickness and
      bladder wall mass, both of which have been associated with outflow obstruction.

PMID- 16985852
TI  - The aging bladder.
AB  - Although it is well established that lower urinary tract symptoms increase in
      frequency with aging, there are few studies of the mechanisms that underlie
      bladder dysfunction. Age-related reduction in bladder capacity, uninhibited
      contractions, decreased urinary flow rate, diminished urethral pressure profile,
      and increased postvoid residual volume warrant investigation and require
      differentiation between symptoms associated with aging and those related to
      comorbid conditions. Here, the current data are reviewed, including those from
      muscle bath investigations of bladder tissue contractility, in vivo studies using
      animal models, and clinical studies in the aging population.

PMID- 16985854
TI  - The role of the primary care physician in the management of bladder dysfunction.
AB  - Urinary incontinence is a major health challenge for primary care physicians.
      Unfortunately, the majority of incontinent patients remain untreated. Primary
      care physicians are ideally positioned to screen for and manage urinary
      incontinence. A knowledge of basic micturition physiology is important for the
      physician to accurately identify the cause of incontinence and arrive at the
      correct treatment course. To this end, this article reviews the physiology of the
      lower urinary tract, describes the clinical types of urinary incontinence, and
      outlines a stepwise approach for the primary care physician to the basic
      evaluation and management of patients with this condition.

PMID- 16985855
TI  - Evaluating men with benign prostatic hyperplasia.
AB  - The clinical manifestations of benign prostatic hyperplasia (BPH) include lower
      urinary tract symptoms (LUTS), poor bladder emptying, urinary retention, detrusor
      instability, urinary tract infection, hematuria, and renal insufficiency.
      However, the majority of men with BPH present with LUTS only. Because LUTS can
      indicate a variety of conditions, evaluation of symptomatic men must first aim to
      identify or exclude BPH and, if present, assess its severity. It is important to
      assess symptom severity at baseline and during follow-up, using the American
      Urological Association Symptom Index or the International Prostate Symptom Score.
      Further testing can then be tailored to narrow the diagnosis and guide treatment
      decisions. Factors such as patient age and concomitant malignancy will also
      affect management, but the main goal of treatment remains the improvement of
      quality of life for the patient.

PMID- 16985856
TI  - Success and failure of single-modality treatment for early prostate cancer.
AB  - Many men who undergo radical prostatectomy or radiotherapy for early prostate
      cancer have an excellent outcome; however, a significant proportion subsequently
      experience disease recurrence and/or cancer-related death. Adjuvant hormonal
      therapy after treatment of curative intent is given with the aim of eradicating
      undetected cancer cells outside the surgical margins or radiation field and/or
      micrometastatic disease. In the analogous setting of early breast cancer,
      adjuvant hormonal therapy is already established as standard care. Efficacy and
      tolerability data from the ongoing bicalutamide ('Casodex') Early Prostate Cancer
      program are expected to determine the role of adjuvant hormonal therapy with
      antiandrogens in early prostate cancer.

PMID- 16985857
TI  - Bicalutamide adjuvant to radical prostatectomy.
AB  - Prostate cancer recurrence affects up to 50% of men in the first 10 years after
      radical prostatectomy for clinically localized disease. New treatment approaches
      that reduce this risk are needed. Current published data on the use of adjuvant
      hormonal therapy in the post-radical prostatectomy setting are limited. New data
      from the bicalutamide (Casodex) Early Prostate Cancer program show that
      bicalutamide 150 mg/d, given as immediate adjuvant treatment, produces clear
      benefits with respect to both progression-free survival and prostate-specific
      antigen progression when compared with standard management with radical
      prostatectomy. The greatest improvement of progression-free survival was observed
      in patient subgroups at highest risk.

PMID- 16985858
TI  - Immediate Treatment with Bicalutamide, 150 mg/d, Following Radiotherapy in
      Localized or Locally Advanced Prostate Cancer.
AB  - Previous studies and meta-analyses have made it clear that some subgroups of
      prostate cancer patients who have received radiotherapy should benefit from
      immediate adjuvant hormonal therapy. A cohort totaling 1370 patients who received
      radiotherapy for early nonmetastatic prostate cancer is currently enrolled in
      three ongoing, randomized, double-blind, placebo-controlled trials investigating
      the role of bicalutamide ('Casodex') 150 mg/d as adjuvant to standard care (the
      bicalutamide Early Prostate Cancer program). At preliminary analysis, conducted
      after a median follow-up of 3 years, adjuvant therapy with bicalutamide 150 mg/d
      significantly reduced the risk of objective progression by 37% compared with
      radiotherapy alone (HR 0.63, 95% CI, 0.46-0.85, P = .0024). Initial results
      demonstrate that bicalutamide 150 mg/d given as immediate adjuvant therapy
      following radiotherapy in men with early nonmetastatic prostate cancer has
      benefits over radiotherapy alone.

PMID- 16985859
TI  - Management of clinically localized prostate cancer.
AB  - Critics of screening have stated that early detection of prostate cancer does not
      necessarily reflect a diminishing death rate from the disease. However, several
      recent reports have demonstrated that the death rate from prostate cancer is
      decreasing, representing the most compelling validation for aggressive screening.
      Prostate cancer can be halted only if there is no evidence of systemic or
      regional metastases and the disease is confined to the surgical field or the
      radiation template. Surgeons and radiation oncologists must make a concerted
      effort to exclude men with regional and systemic metastases who are unlikely to
      benefit from treatment. With the widespread acceptance of prostate-specific
      antigen screening, a greater proportion of men are being diagnosed with
      clinically localized prostate cancer. Both radical prostatectomy and radiation
      therapy are able to halt disease spread in this significant subset of men, but
      survival outcomes indicate that radical prostatectomy is a more reliable
      treatment than radiation therapy for clinically localized prostate cancer.
      Overall, the immediate treatment-related morbidity of radical prostatectomy and
      radiation therapy in the modern era is quite low. Radical prostatectomy and
      radiation therapy appear to have a similar impact on continence and erectile
      function. There is a need for neoadjuvant and adjuvant therapies that can be
      utilized in those cases where radical prostatectomy and radiation are less likely
      to completely eradicate or destroy the cancer.

PMID- 16985860
TI  - The pathophysiology of stress urinary incontinence: a historical perspective.
AB  - This article provides a historical perspective on the evolution of theories
      regarding the pathophysiology of stress urinary incontinence (SUI). The
      progression of these theories has followed the development of the diagnostic
      technologies that have provided insight into different aspects of urethral
      dysfunction. The earliest theories tied SUI to anatomic failure of urethral
      support. Recognition that anatomic failure impacted the interplay of intra
      abdominal pressure and the bladder and urethra led to theories focused on the
      dynamic interaction between the bladder and urethral pressures. Investigators
      then began to recognize the importance of urethral sphincteric dysfunction. More
      recently, investigators have attempted to combine the anatomic and functional
      etiologies into a consolidated theory. These efforts point to a multi-factorial
      etiology of SUI. Continuing research has provided new insight into the
      neurophysiology of urethral function, opening new avenues for tailoring therapy
      for SUI.

PMID- 16985861
TI  - Neurophysiology of stress urinary incontinence.
AB  - Stress urinary incontinence (SUI) involves involuntary leakage of urine in
      response to abdominal pressure caused by activities such as sneezing and
      coughing. The condition affects millions of women worldwide, causing physical
      discomfort as well as social distress and even social isolation. Until recently,
      SUI was approached by clinicians as a purely anatomic problem requiring
      behavioral or surgical therapy. Over the past several years, extensive basic and
      clinical research in the field of neurourology has enhanced our understanding of
      the complex neural circuitry regulating normal function of the lower urinary
      tract. As a result, novel concepts have emerged regarding possible neurologic
      dysfunctions that might underlie the development of SUI, as well as potential
      novel strategies for pharmacologic therapy. This article reviews the normal
      neurophysiologic control of lower urinary tract function and considers potential
      pharmacologic approaches to correcting SUI.

PMID- 16985863
TI  - The definition, prevalence, and risk factors for stress urinary incontinence.
AB  - Stress urinary incontinence (SUI) has an observed prevalence of between 4% and
      35%. Whereas the clinical definition of SUI has been established by the
      International Continence Society, the epidemiologic definition has not been
      established, leading to a broad disparity in reported prevalence rates. Numerous
      risk factors for SUI have been identified. Aging, obesity, and smoking appear to
      have consistent causal relationships with the condition, whereas the roles of
      pregnancy and childbirth remain controversial. The prevalence of many of these
      risk factors is increasing in the adult female population of the United States.
      These population changes, combined with increasing physician awareness and the
      availability of nonsurgical therapy, will likely increase the number of women
      receiving care for SUI over the next 3 decades.

PMID- 16985862
TI  - Treatment options for stress urinary incontinence.
AB  - Treatment options for stress urinary incontinence (SUI) in women are designed to
      prevent the involuntary loss of urine from the urethra during increases in
      intraabdominal pressure that occur during physical activity, coughing, or
      sneezing. Effective nonsurgical therapies include behavioral therapy (eg, bladder
      training, fluid and dietary modification) and drug therapy. Surgical therapy for
      this condition has existed for well over 100 years. Currently, approximately 200
      different surgical procedures have been described. Because of the physiologic
      risks inherent in surgical procedures, the cost of hospitalization, and the loss
      of productivity during convalescence, surgeons continue to modify their
      techniques to improve efficacy, safety, and cost-effectiveness, and to minimize
      invasiveness. No single procedure or intervention is optimal for all patients.
      Having a variety of treatment options offers the possibility of tailoring therapy
      to the desires and needs of the individual patient. The key to an optimal
      therapeutic outcome is an accurate diagnosis combined with the selection of an
      appropriate intervention that is acceptable to the patient after balancing
      multiple factors.

PMID- 16985864
TI  - Duloxetine: a new pharmacologic therapy for stress urinary incontinence.
AB  - The dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitor duloxetine shows
      promise as a pharmacologic therapy for stress urinary incontinence. This agent
      modulates lower urinary tract function through selective inhibition of 5-HT and
      NE receptor sites. It works centrally at Onuf's nucleus to increase activity of
      the pudendal nerve. Duloxetine facilitates sphincter activity during urine
      storage but not during voiding, maintaining the bladder-sphincter synergy.
      Because it inhibits both 5-HT and NE reuptake, duloxetine appears to offer an
      advantage over agents that inhibit reuptake of a single neurotransmitter.

PMID- 16985865
TI  - Duloxetine: a summary of published clinical experience.
AB  - Effective oral therapy for genuine stress urinary incontinence (SUI) in women
      has, to date, been an unattainable goal. Although oral pharmacologic agents have
      been used for this condition, none has ultimately been successful, because of
      side effects, lack of efficacy, or problematic compliance with drug ingestion.
      The availability of an effective oral agent for SUI would increase the range of
      therapeutic options for symptom management and possibly make treatment accessible
      to more women who otherwise feel that surgical therapy is not an option because
      of social, personal, or medical reasons. Duloxetine is a selective serotonin (5
      HT) and norepinephrine reuptake inhibitor that has been shown to increase
      rhabdosphincter activity. Rhabdosphincter contractility changes are thought to
      occur as the result of increased stimulation of alpha(1)-adrenergic and 5-HT(2)
      receptors in the sacral spinal cord, resulting in increased efferent pudendal
      nerve activity, producing increased pelvic floor tonus. Two large-scale studies
      have been completed employing subjective and objective outcomes to assess the
      therapeutic index of duloxetine as a therapy for SUI.

PMID- 16985866
TI  - Cryosurgery of the prostate: techniques and indications.
AB  - Cryosurgical ablation of the prostate (CSAP) is indicated for patients with high
      stage and high-grade tumors, patients with recurrent/persistent carcinoma of the
      prostate after external radiation therapy or brachytherapy, and others. At
      Allegheny General Hospital, CSAP is performed as follows: the patient is prepped
      in an exaggerated lithotomy position; a volumetric study of the gland is obtained
      with transrectal ultrasound; 5 to 15 cryoneedles are placed (in three to five
      horizontal rows) through a 17-gauge, stepper-mounted template; a cystoscopy is
      performed; and a urethral warming catheter is introduced. The rows of cryoneedles
      are then activated from anterior to posterior, and generally two freeze-thaw
      cycles are used. In longer glands, a pullback of the cryoneedles might be needed
      to completely cover the apical portion of the gland. The skills required for CSAP
      are identical to those required for brachytherapy needle placement, thus the
      training required for physicians already proficient in brachytherapy is
      minimized.

PMID- 16985867
TI  - Salvage cryosurgery of the prostate after radiation failure.
AB  - Radiation therapy is one option for patients with localized prostate cancer.
      Despite advances in delivering radiation to the prostate gland with therapies
      such as brachytherapy and/or external beam radiation therapy, urologists will be
      faced with managing patients with rising prostate-specific antigen values and
      with positive biopsy results secondary to radiation-recurrent prostate cancer. If
      the cancer is detected early, salvage therapy can be initiated. Since salvage
      prostatectomy is associated with significant morbidity, patients are often left
      with the option of either watchful waiting or temporary palliation with hormone
      deprivation therapy, with its attendant toxicity. The introduction of third
      generation cryotechnology using 17-gauge CryoNeedlestrade mark (Oncura, Inc.,
      Plymouth Meeting, PA) and the recent modifications in the technique of salvage
      cryosurgery have enabled cryosurgeons to eradicate these tumors safely and with
      significantly decreased morbidity. Selection and management of patients, as well
      as the contemporary results of salvage cryosurgery, are discussed in this
      article.

PMID- 16985868
TI  - Minimally Invasive Therapy for Prostate Cancer: Use of Nomograms to Counsel
      Patients about the Choice and Probable Outcome of Therapy.
AB  - Despite dramatic and recently accelerated advances in the reduction of morbidity
      linked to radical prostatectomies, significant short- and long-term morbidity is
      still associated with this surgical procedure. Currently both surgical and
      nonsurgical minimally invasive options are available for men with clinically
      localized prostate cancer, including laparoscopic and robotic radical
      prostatectomy, brachytherapy, and cryosurgical ablation of the prostate, with
      others, such as high intensity focused ultrasound, under investigation. In
      continued efforts to improve patient outcomes and to tailor treatment options to
      individual patient circumstances, nomograms have been developed and are
      increasingly being used by physicians and patients, alike, to guide therapeutic
      choices at each stage of disease. This tool predicts the possibility of
      successful treatment for the patient based on factors such as prostate-specific
      antigen levels, clinical stage of disease, and biopsy results. The current and
      future development, design, availability, and use of nomograms is described along
      with the historic and newer minimally invasive treatment options for prostate
      cancer.

PMID- 16985869
TI  - Advances in brachytherapy.
AB  - During the past 15 years, permanent seed brachytherapy for prostate cancer has
      advanced significantly in all areas, including patient selection, treatment
      planning, technique, and technology (eg, seeds stranded in Vicryl suture). These
      improvements have made transperineal seed implantation an accurate and practical
      treatment option for men with low-, intermediate-, and high-risk disease. Because
      of the evidence that the various treatment options for prostate cancer are likely
      to be equally successful in terms of long-term cancer control, continuing efforts
      focus on enhancing the quality of life of implant patients.

PMID- 16985870
TI  - Permanent prostate brachytherapy: the significance of postimplant dosimetry.
AB  - Recent developments in imaging science and treatment-planning software allow for
      accurate postimplant dosimetric assessment in all patients after prostate
      brachytherapy. This article reviews the available data correlating cancer control
      and morbidity with dosimetric quantifiers obtained from postimplant dosimetric
      assessment after prostate brachytherapy. Continued collection of dosimetric data
      in patients treated with prostate brachytherapy will allow for further
      refinements in the technique, leading to continued high rates of cure with
      increasingly lower rates of morbidity.

PMID- 16985871
TI  - Cancer cryotherapy: evolution and biology.
AB  - Since the inception of cryosurgery in the 1850s, landmark advances in chemistry,
      physics, materials science, and biology have culminated in the sophisticated
      cryosurgical devices currently in use. Effective cryosurgical tissue injury
      depends on four criteria: 1) excellent monitoring of the process; 2) fast cooling
      to a lethal temperature; 3) slow thawing; and 4) repetition of the freeze-thaw
      cycle. Meeting these criteria depends on understanding the imaging technology
      used to visualize the iceball, the type of cryogen used, the size of the probe,
      and probe arrangement. Third-generation cryosurgical equipment offers advantages
      over previous designs. These machines rely on argon for freezing but also use
      helium to warm probes and accelerate the treatment process, and they offer
      additional safety by being able to rapidly arrest iceball formation. Metallurgic
      advances have led to the development of thinner probes, which have been easily
      adapted to perineal templates similar to those used for prostate brachytherapy.

PMID- 16985873
TI  - Tegresstrade mark Urethral Implant Phase III Clinical Experience and Product
      Uniqueness.
AB  - Advances in materials technology, coupled with a heightened understanding of
      wound healing and tissue-materials interactions in the lower urinary tract, have
      led to the development of a variety of new urethral bulking agents that are
      expected to be available in the near future. Experience with such bulking agents
      continues to grow and study results are disseminated as more clinical trials are
      initiated and completed. The intention of this report is to review the
      characteristics and initial clinical results for one of these new agents:
      Tegresstrade mark Urethral Implant (C. R. Bard, Inc., Murray Hill, NJ). This
      material, with unique phase-change properties upon exposure to body temperature
      fluids, offers ease of injection and requires less volume for clinical effect
      than bovine collagen. Additionally, Tegress Urethral Implant performance in
      clinical trials has suggested improved durability and correspondingly higher
      continence and improvement rates versus bovine collagen. As these materials
      evolve, an understanding of preferential implant techniques is being gained also.
      Delivery method and implant site may prove to substantially alter the biologic
      activity of these compounds. As outlined in this review, experience with Tegress
      Implant resulted in changes in delivery technique that translated into improved
      materials and tissue interaction.

PMID- 16985872
TI  - Current use of injectable agents for female stress urinary incontinence.
AB  - Injectable materials of various types have been used for decades as an
      alternative to surgery for the treatment of stress urinary incontinence. Their
      success stems from their ability to improve intrinsic sphincter function, and
      patients with hypermobility may benefit as well. Nevertheless, the ideal agent
      has yet to be discovered, and surgery still may be necessary after treatment in
      some patients. Results vary among the different materials used, and safety,
      durability, and cost-effectiveness are important areas of concern in which more
      research is needed.

PMID- 16985874
TI  - Bulking agents in the treatment of stress urinary incontinence: history,
      outcomes, patient populations, and reimbursement profile.
AB  - Stress urinary incontinence (SUI) can be defined as involuntary loss of urine
      during a period of increased abdominal pressure and in the absence of detrusor
      activity. Bulking agents used in the urethra are one of the newer but established
      technologies for the treatment of SUI. An understanding of the demographics of
      SUI will help in the selection of patients for bulking agent therapy. Knowledge
      of available materials, including their positive and negative aspects, is also
      required. Autologous fat, silicone beads, collagen, carbon particles, and
      polytetrafluoroethylene paste have all demonstrated success to some degree, but
      none have met both criteria for success (remaining efficacious over time and
      maintaining a low side-effect profile). An implantable solution of ethylene vinyl
      alcohol suspended in dimethyl sulfoxide, currently in clinical testing and
      review, shows minimal foreign body reaction and is one option being investigated
      to address patient needs for improved bulking therapy.

PMID- 16985875
TI  - Prostatic intraepithelial neoplasia: an overview.
AB  - Prostatic intraepithelial neoplasia (PIN) is the most established precursor of
      prostatic carcinoma. The presence of prominent nucleoli within an existing duct
      structure is an easy way to identify the disorder. Four main patterns of high
      grade PIN (HGPIN) have been described: tufting, micropapillary, cribriform, and
      flat. In addition to exhibiting similar cytologic features, both HGPIN and
      prostatic carcinoma are associated with increased incidence and severity with
      age, and with high rates of occurrence in the peripheral zone of the prostate.
      HGPIN and prostate cancer share genetic and molecular markers as well, with PIN
      representing an intermediate stage between benign epithelium and invasive
      malignant carcinoma. The clinical significance of HGPIN is that it identifies
      patients at risk for malignancy. With the increased use of extended biopsy
      protocols, clinicians are more likely to identify HGPIN and less likely to miss
      concurrent carcinoma. Androgen deprivation therapy decreases the prevalence and
      extent of PIN, and may play a role in chemoprevention. Preliminary studies
      suggest that selective estrogen receptor modulators may also prevent the
      progression of HGPIN to prostate cancer.

PMID- 16985876
TI  - Drug therapies for eradicating high-grade prostatic intraepithelial neoplasia in
      the prevention of prostate cancer.
AB  - High-grade prostatic intraepithelial neoplasia (HGPIN) is a precursor to invasive
      prostate cancer observed as an isolated entity in a growing subset of men
      undergoing prostate biopsy. The presence of HGPIN predicts an increased risk of
      1) coexisting occult prostate cancer at baseline and 2) delayed progression to
      prostate cancer. As such, men with HGPIN represent a population at high risk for
      the development of prostate cancer. Because the current recommended therapy is
      observation and delayed-interval biopsies until cancer develops, a well-tolerated
      therapeutic agent capable of interrupting the progression of HGPIN to cancer is
      highly desirable. Given the known cancer-stimulatory effects of estrogens in the
      prostate, the use of selective estrogen receptor modulators (SERMs) to provide an
      antiestrogen effect represents a novel strategy for prostate cancer prevention.
      Recent phase II data from trials using toremifene in the treatment of men with
      HGPIN validate the use of SERMs as a rational and provocative strategy for the
      prevention of prostate cancer.

PMID- 16985877
TI  - Selective estrogen receptor modulators to prevent treatment-related osteoporosis.
AB  - The intended therapeutic effect of gonadotropin-releasing hormone (GnRH) agonists
      is hypogonadism, which is a leading cause of osteoporosis in men. Consistent with
      this observation, GnRH agonists decrease bone mineral density and increase
      fracture risk in men with prostate cancer. GnRH agonists markedly decrease serum
      levels of both testosterone and estrogen. Estrogens play a central role in
      homeostasis of the normal male skeleton, and the available evidence suggests that
      estrogen deficiency rather than testosterone deficiency accounts for the adverse
      skeletal effects of GnRH agonists. The central role of estrogens in male bone
      metabolism provides a strong rationale to evaluate selective estrogen receptor
      modulators for prevention of treatment-related osteoporosis in men with prostate
      cancer. Preliminary evidence suggests that both raloxifene and toremifene
      increase bone mineral density in GnRH agonist-treated men. An ongoing pivotal
      study will evaluate the effects of toremifene on fractures and other
      complications of GnRH agonists in men with prostate cancer.

PMID- 16985878
TI  - The role of estrogens in prostate carcinogenesis: a rationale for
      chemoprevention.
AB  - Estrogens as hormonal therapy, particularly diethylstilbestrol, are effective
      against androgen-dependent prostate cancer, but paradoxically estrogens might
      also be involved in the causation of this malignancy. Therefore, antiestrogens
      have been suggested as both a chemopreventive and chemotherapeutic treatment,
      thereby inhibiting the development and progression of prostate cancer. This
      review addresses the role of estrogens in prostate carcinogenesis and prostate
      cancer progression and examines the rationale for using antiestrogenic agents in
      chemoprevention of prostate cancer.

PMID- 16985879
TI  - Maximum androgen blockade: a clinical update.
AB  - Maximal androgen blockade (MAB) therapy for metastatic prostate cancer has
      advanced in recent years with the discovery of luteinizing hormone-releasing
      hormone agonists (LHRH), the development of LHRH analogues, and the discovery of
      antiandrogens. Of 36 studies of MAB therapy performed from 1980 to 1991, 3 showed
      a statistically significant increase in survival with MAB versus castration
      alone. Because of the large number of studies showing no benefit from MAB, a meta
      analysis was performed on 27 studies. This meta-analysis demonstrated a survival
      benefit from MAB of only 3%; however, a critical review of the analysis revealed
      major flaws that raise serious questions regarding the validity of its findings.
      In addition, the fact remains that the longest survival reported for patients
      with stage M1 prostate cancer was 35 to 36 months, whereas the longest survival
      for castration alone was 32 to 33 months. Therefore, when physicians discuss
      treatment choices for patients with metastatic disease, MAB should remain a
      reasonable option.

PMID- 16985880
TI  - Addressing the needs of the high-risk prostate cancer patient.
AB  - For prostate cancer patients with a substantial risk of posttherapy progression,
      managing the disease with a risk-stratified approach and multimodal therapy is an
      evolving concept. Through an analysis of prostate-specific antigen (PSA) level,
      biopsy Gleason score, and clinical stage, investigators have been able to define
      low-, intermediate-, and high-risk disease in terms of the risk of progression
      after definitive local therapy. High-risk features include a PSA level greater
      than 20 ng/mL, a Gleason score of 8 to 10 or a clinical stage of T2c or higher.
      Because high-risk men treated by surgery or radiation therapy are at increased
      risk of progression and death from prostate cancer over the ensuing decade,
      various strategies have been used to improve their rates of disease-free
      progression and overall survival. Radiation therapy combined with hormonal
      therapy, radical prostatectomy combined with hormonal therapy or adjuvant
      radiation, and other approaches, such as chemo-hormonal therapy, are either under
      study or have been supported in randomized clinical trials. This review
      summarizes the current standard approaches to treating the man with high-risk
      disease.

PMID- 16985881
TI  - The effective management of biochemical recurrence in patients with prostate
      cancer.
AB  - Prostate-specific antigen (PSA) testing has become the primary method of
      monitoring patients following definitive therapy for clinically localized
      prostate cancer. After surgery, an immediate detectable rise in PSA is correlated
      with subsequent local recurrence and/or metastasis. Following radiation therapy,
      biochemical failure is defined as 3 consecutive rises in PSA above the nadir.
      Treatment of postoperative or postradiation PSA recurrence involves several
      modalities, including luteinizing hormone-releasing hormone agonists. Although
      studies have demonstrated the advantages of early hormone therapy, they have not
      addressed at what PSA level treatment should begin. A better understanding of
      PSA's kinetics will lead to a sense of when to begin treatment and when watchful
      waiting is the more appropriate course.

PMID- 16985882
TI  - Comparison of single-agent androgen suppression for advanced prostate cancer.
AB  - Gonadotropin-releasing hormone (GnRH) agonists are the agents of choice for
      achieving androgen suppression in men with advanced prostate cancer. The GnRH
      agonists that have been developed and marketed for prostate cancer are
      leuprolide, goserelin, triptorelin, and histrelin. So far, there have been few
      randomized studies directly comparing these single-agent therapies; however, the
      literature and the data on file with the Food and Drug Administration suggest
      that triptorelin may be more reliable than leuprolide in maintaining castration
      levels of serum testosterone. The clinical significance of this benefit remains
      to be proven.

PMID- 16985883
TI  - Adverse events associated with hormonal therapy for prostate cancer.
AB  - With expanding indications for androgen deprivation therapy for the treatment of
      prostate cancer, it is imperative that health care providers be cognizant of the
      possible adverse effects of therapy, as well as their prevention and treatment.
      Neurologic and psychiatric effects include depression and declines in cognitive
      function. Musculoskeletal effects of hormonal therapy include osteoporosis,
      decrease in muscle mass, and fatigue. Gynecomastia, weight gain, and erectile
      dysfunction are also seen, as are hematologic effects. Further research is needed
      to evaluate alternative forms of therapy, such as intermittent hormonal
      deprivation and antiandrogen monotherapy.

PMID- 16985884
TI  - Reimbursement issues with hormonal therapies for prostate cancer.
AB  - Reimbursement issues surrounding the treatment of prostate cancer with hormonal
      therapies have changed dramatically in the past 2 years. The ultimate goal for
      urologists when making treatment decisions regarding LHRH agonist use is to
      continue to provide hassle-free, complete care for patients, including whatever
      medications they need. This is still fully possible under the new rules without
      sacrificing the opportunity to profit from office-based administration of
      injectable medications.

PMID- 16985885
TI  - Primary bladder neck obstruction in men and women.
AB  - Primary bladder neck obstruction (PBNO) is a condition in which the bladder neck
      does not open appropriately or completely during voiding. Although the true
      prevalence of PBNO is difficult to ascertain, studies in both men and women with
      voiding dysfunction demonstrate a marked prevalence of the condition. Symptoms
      caused by PBNO include storage symptoms (frequency, urgency, urge incontinence,
      nocturia) and voiding symptoms (decreased force of stream, hesitancy, incomplete
      emptying). There are multiple theories as to the etiology of PBNO, including
      muscular and neurologic dysfunction and fibrosis. The diagnosis of PBNO can be
      made precisely with videourodynamics, urodynamic testing with simultaneous
      pressure-flow measurement, and visualization of the bladder neck during voiding.
      Treatments vary from watchful waiting to medical therapy to surgery, depending on
      the severity of symptoms, urodynamic findings, and response to therapy. This
      article reviews the current state of the art with respect to the prevalence,
      etiology, diagnosis, and treatment of PBNO.

PMID- 16985886
TI  - alpha-Blockers for Treatment of the Prostatitis Syndromes.
AB  - The prostatitis syndromes are among the most common and frustrating clinical
      challenges for urologists in outpatient practice. Available treatment, especially
      for the chronic prostatitis syndromes, is poor, with no standard therapy
      producing significant cure rates. alpha-Blocker therapy has been advocated (with
      various levels of evidence) as a treatment modality for all categories of the
      prostatitis syndromes. This article reviews the evidence supporting the use of
      alpha-blocker therapy in patients with prostatitis. Further trials of longer
      duration, perhaps employing combination therapies, are indicated to better
      evaluate the role of alpha-blockers in the management of the prostatitis
      syndromes.

PMID- 16985887
TI  - Managing and preventing acute urinary retention.
AB  - Acute urinary retention (AUR), an uncomfortable and potentially dangerous
      condition, often occurs in men who have benign prostatic hyperplasia. Although
      the reported incidence of AUR varies in the literature, there are a number of
      events that are known to precipitate episodes of AUR, including ingestion of
      certain agents, infection, general anesthesia, and performance of various
      diagnostic genitourinary procedures. Because it is preferable to avoid the need
      for catheterization (and the associated risks) in men at high risk for AUR,
      certain measures have been studied as means to prevent AUR episodes.
      Specifically, alpha-blockers and 5-alpha-reductase inhibitors have been shown to
      reduce the incidence of initial and subsequent AUR episodes in certain at-risk
      men.

PMID- 16985888
TI  - Sexual Function and alpha-Blockers.
AB  - Community-based studies and surveys have found an association between lower
      urinary tract symptoms (LUTS) and sexual dysfunction, in particular, erectile
      dysfunction (ED). The link between ED and LUTS has biologic plausibility. The
      following 4 theories have been used to explain how these disorders interrelate:
      1) decreased or altered nitric oxide synthase/nitric oxide levels in the prostate
      and penile smooth muscle; 2) autonomic hyperactivity effects on LUTS, prostate
      growth, and ED; 3) increased Rho-kinase activation/endothelin activity; and 4)
      prostate and penile atherosclerosis. The relationship of LUTS and sexual
      dysfunction suggests that treatment of one condition may impact the other.

PMID- 16985889
TI  - alpha-Blocker Therapy: Current Update.
AB  - alpha-Blockade is the predominant form of medical therapy for the treatment of
      symptomatic bladder outlet obstruction due to benign prostatic hyperplasia (BPH).
      Recent research has shown that there is a series of alpha(1) receptor subtypes
      present in humans and that the alpha(1A) subtype appears to play a primary role
      in mediating prostatic smooth muscle contraction. Recent interest has therefore
      focussed on the development of agents specific to this alpha(1A) receptor
      subtype. The approval by the Food and Drug Administration of tamsulosin, an
      alpha(1A)-specific antagonist, offers physicians in the United States the
      opportunity to prescribe a selective alpha(1)-blocker for the treatment of BPH.
      Tamsulosin offers a pharmacologic means to better target alpha-blockade
      specifically to the prostatic smooth muscle and spare the vascular smooth muscle.
      Use of this agent has resulted in a lower incidence of clinically relevant
      effects on blood pressure or heart rate and minimal cardiovascular adverse
      effects.

PMID- 16985890
TI  - Combination medical therapy for lower urinary tract symptoms and benign prostatic
      hyperplasia.
AB  - Medical therapy with alpha-adrenergic receptor blockers and 5-alpha-reductase
      inhibitors is currently considered first-line treatment for men with moderate to
      severe symptoms of benign prostatic hyperplasia (BPH). Given the success that has
      been realized with monotherapy with each of these agents, interest in combination
      therapy has grown. Large-scale trials to test the efficacy of such combinations
      are lacking; however, a few studies, such as the Medical Therapy of Prostatic
      Symptoms trial, have yielded results indicating that the 2 types of agents
      combined can reduce the risk of symptomatic progression and acute urinary
      retention, as well as the need for invasive therapy. More research is needed to
      clarify the roles of these agents in the treatment of BPH and in the optimization
      of patient quality of life.

PMID- 16985891
TI  - BPSA: A Novel Serum Marker for Benign Prostatic Hyperplasia.
AB  - Free prostate-specific antigen (fPSA) testing was developed and approved for
      widespread use despite the lack of knowledge regarding the underlying biologic
      basis for its ability to discriminate between benign prostatic hyperplasia (BPH)
      and prostate cancer. We hypothesized that the relationship of total PSA to
      prostate volume was due primarily to the fPSA component of serum PSA, and we
      studied the molecular forms of PSA found in prostate tissue. Later, more
      sophisticated studies resulted in the discovery of BPSA (benign PSA), a novel
      form of fPSA associated with nodular hyperplasia of the transition zone (TZ). We
      found that the serum BPSA level is highly correlated with TZ and total prostate
      volume. In our most recent studies, we found that BPSA correlates better with TZ
      volume than does PSA and can predict clinically significant prostate enlargement
      better than PSA or fPSA. Furthermore, the relation of BPSA and fPSA to total
      prostate and TZ volumes is independent of age.

PMID- 16985892
TI  - A review of surgical techniques for radical prostatectomy.
AB  - Since the early 20th century, radical prostatectomy has been used in the
      treatment of prostate cancer. However, before the widespread acceptance of
      prostate-specific antigen screening, the majority of cancers were clinically
      advanced and not amenable to cure, so relatively few men were candidates for this
      procedure. Modern advances have contributed dramatically to the reduction of
      complications and morbidity associated with radical prostatectomy. As a result,
      the procedure has become the most common treatment selected by men with localized
      prostate cancer. This article reviews several issues regarding radical
      prostatectomy, including surgical techniques, cancer control, intraoperative
      localization of the cavernous nerves, patient selection, and laparoscopic versus
      robotic approaches.

PMID- 16985893
TI  - Cavernous nerve stimulation and interposition grafting: a critical assessment and
      future perspectives.
AB  - The sexual dysfunction that results from radical prostatectomy for carcinoma of
      the prostate is well established, with the degree of macroscopic preservation of
      the cavernous nerves tied to the degree of postoperative recovery of erectile
      function that is possible. In addition to the use of preoperative neuroprotective
      drugs and postoperative erectogenic agents, intraoperative nerve stimulation and
      grafting offer promise. Nerve stimulation may serve as a predictor of
      postoperative potency, and nerve grafting offers a potential way to correct the
      damage that occurs during wide resection. This article reviews the current
      literature on these intraoperative measures and discusses the need for additional
      studies of their potential benefits in prostatectomy candidates.

PMID- 16985894
TI  - Neuroregenerative strategies after radical prostatectomy.
AB  - Patients with erectile dysfunction (ED) following radical prostatectomy (RP)
      continue to present to practicing urologists. Although nerve-sparing RP has
      decreased the rates of ED significantly, new therapies for cavernosal nerve
      protection and recovery are now being developed. This report discusses the many
      agents available in neuroregeneration and neuroprotection to aid in the recovery
      of erectile function. Multiple agents and strategies have been used for
      neuroprotection and neuroregeneration of the cavernosal nerve following RP and in
      nerve injury models. Many of these agents display promise for the treatment of
      impotence. Early treatment for patients recovering from RP is becoming the
      standard of care. Natural recovery of erections may take as long as 18 to 24
      months post RP; however, treatment plans may reduce the time to erectile
      recovery.

PMID- 16985895
TI  - Sexual dysfunction after radical prostatectomy.
AB  - Sexual dysfunction associated with radical retropubic prostatectomy (RRP) may
      start before the surgery. Men undergoing RRP frequently have some degree of
      sexual dysfunction. In addition to the psychological stress of the diagnosis, the
      biopsy may itself have a detrimental effect. After surgery, all men will
      experience loss of ejaculate, because the organ responsible for ejaculate has
      been removed. Orgasm quality is adversely affected in many men. Erectile
      dysfunction is immediate and recovery from it is slow. Initially,
      phosphodiesterase (PDE)-5 inhibitors do not work, and they take up to 18 months
      for their effect to be maximized. Younger men who have had bilateral nerve
      sparing procedures respond the best. Combination treatment with prostaglandin E1
      or high-dose PDE-5 inhibitors may provide salvage therapy when initial PDE-5
      inhibitor therapy has failed.

PMID- 16985896
TI  - PDE-5 Inhibitor Therapy for Erectile Dysfunction Secondary to Nerve-Sparing
      Radical Retropubic Prostatectomy.
AB  - The majority of patients receiving therapy for erectile dysfunction (ED)
      following post-radical retropubic prostatectomy (RRP) are treated with
      phosphodiesterase (PDE)-5 inhibitors, which seem to have variable efficacy in
      this population. So far, the only head-to-head trials with PDE-5 inhibitors have
      been in general ED patients and not in post-RRP patients. Both vardenafil and
      tadalafil failed to meet statistical noninferiority to sildenafil in head-to-head
      trials. To date, only sildenafil has demonstrated efficacy in the prevention of
      post-nerve-sparing RRP ED. The selection of a PDE-5 inhibitor requires
      consideration of the patient's sexual activity pattern as well as the drug's
      efficacy and its ability to meet the patient's expectations. In this regard,
      sildenafil continues to account for almost 70% of PDE-5 inhibitor prescriptions
      in the United States.

PMID- 16985898
TI  - Penile prosthesis implantation for end-stage erectile dysfunction after radical
      prostatectomy.
AB  - When erectile dysfunction occurs after radical prostatectomy and
      phosphodiesterase-5 inhibitor therapy fails, second-line therapies such as vacuum
      constriction devices, intraurethral prostaglandins, and penile injection therapy
      should be offered. When second-line therapies are not effective or acceptable to
      the man and his partner, penile prosthesis implantation becomes the treatment of
      choice. Today's 3-piece inflatable devices offer flaccidity and erection that
      approach the natural state. Design improvements have resulted in devices that
      have freedom from mechanical failure ranging from 92% to 94%. Antibiotic and
      hydrophilic coatings have reduced infection rates.

PMID- 16985897
TI  - Advances in the Management of Post-Radical Prostatectomy Erectile Dysfunction:
      Treatment Strategies When PDE-5 Inhibitors Don't Work.
AB  - Phosphodiesterase type-5 (PDE-5) inhibitors have revolutionized the treatment of
      post-radical prostatectomy erectile dysfunction. For those patients who undergo a
      non-nerve-sparing radical prostatectomy or whose condition fails to respond to
      PDE-5 inhibitors, alternative treatment with intracavernous injection therapy,
      transurethral alprostadil, vacuum erection devices, and recently described
      combination therapy is available. The goals of therapy are to provide the patient
      with a means of obtaining an erection so that the patient and his partner may
      resume sexual relations as soon as possible following radical prostatectomy.
      There is evidence that early institution of treatment may promote improvement in
      the return of spontaneous erections in patients who have undergone nerve
      preservation. In patients who undergo non-nerve-sparing procedures, therapy may
      improve penile rigidity. Intracavernous injection therapy, transurethral
      alprostadil, and vacuum devices are highly effective in the management of post
      prostatectomy erectile dysfunction. High dropout rates, which are not related to
      adverse effects, have been described with all 3 modalities. Pre- and
      postoperative counseling may improve patient and partner satisfaction.

PMID- 16985899
TI  - The evolution of laser therapy in the treatment of benign prostatic hyperplasia.
AB  - The 2 basic principles of laser therapy for benign prostatic hyperplasia (BPH),
      based on the final tissue effect, are laser vaporization and laser coagulation.
      In laser vaporization techniques, higher-density laser thermal energy is used;
      effects range from complete tissue vaporization to incision, resection, or
      enucleation of the obstructing prostatic tissue. Interstitial laser coagulation
      (ILC) requires lower therapeutic temperatures. The urethral preservation and lack
      of tissue evaporation/resection with ILC make this treatment different from
      conventional transurethral free-beam laser prostatectomy. The Indigo(R) Optima
      Laser treatment system is the most widely used ILC system. Unlike other BPH laser
      therapies, Indigo ILC can be satisfactorily performed using pure local anesthesia
      in an office or outpatient setting. Favorable treatment outcomes are seen in a
      large percentage of patients, with minimal adverse events. Such favorable results
      depend on proper surgical technique and operator experience.

PMID- 16985900
TI  - Local anesthesia during interstitial laser coagulation of the prostate.
AB  - With the emergence of minimally invasive therapies for the management of symptoms
      of benign prostatic hyperplasia (BPH), as well as the reality of a changing
      medical economic environment, there is a need for a reliable local anesthesia
      protocol. The protocol described here for prostate anesthetic block is a safe,
      economical, and effective way to perform interstitial laser coagulation and other
      minor endoscopic urologic procedures in the office setting. Most patients
      experience little discomfort and recover quickly, with prompt return to normal
      activities. Urologists should be aware of and comfortable with these techniques.

PMID- 16985901
TI  - A Multicenter Study on the Efficacy and Safety of Interstitial Laser Coagulation
      Versus alpha-Blockade in Subjects With Symptomatic Benign Prostatic Hyperplasia:
      Preliminary Results.
AB  - Significant efforts have been made to develop minimally invasive surgical
      approaches to the treatment of benign prostatic hyperplasia, both to lessen the
      morbidity of the standard operative procedures and to avoid the need for
      continued drug therapy throughout the patient's life. Interstitial laser
      coagulation (ILC) is a minimally invasive procedure that can be performed with
      local, regional, or general anesthesia. With this operator-dependent procedure,
      the surgeon can selectively control placement of the laser fiber to achieve the
      optimum destruction of tissue. Preliminary (6-month) data from a randomized trial
      comparing alpha-blockade with ILC demonstrate that treatment with ILC is
      associated with a clinically significant decrease in American Urological
      Association symptom scores, a result superior to that achieved with an alpha
      blocker.

PMID- 16985902
TI  - Benign prostatic hyperplasia: an overview.
AB  - Despite the deceptively simple description of benign prostatic hyperplasia (BPH),
      the actual relationship between BPH, lower urinary tract symptoms (LUTS), benign
      prostatic enlargement, and bladder outlet obstruction is complex and requires a
      solid understanding of the definitional issues involved. The etiology of BPH and
      LUTS is still poorly understood, but the hormonal hypothesis has many arguments
      in its favor. There are many medical and minimally invasive treatment options
      available for affected patients. In the intermediate and long term, minimally
      invasive treatment options are superior to medical therapy in terms of symptom
      and flow rate improvement; tissue ablative surgical treatment options are
      superior to both minimally invasive and medical therapy.

PMID- 16985903
TI  - Pathophysiology of stress urinary incontinence.
AB  - All cases of stress urinary incontinence (SUI) are not the same; urethral
      pressures, prolapse conditions, and congenital and acquired sphincteric
      dysfunction all contribute to SUI pathophysiology. In order to optimally manage
      SUI, a thorough understanding of the pathophysiology behind the condition is
      necessary. Unsuccessful treatment of incontinence can result from the procedure
      itself or from a poor fit between the patient's condition and the treatment
      chosen. Proper patient evaluation, including videourodynamics and measurement of
      Valsalva leak point pressure, is key to making the best treatment decisions and
      obtaining optimal patient outcomes.

PMID- 16985904
TI  - Management of stress urinary incontinence.
AB  - Although there is renewed interest in conservative therapies for stress urinary
      incontinence, such as pelvic floor exercises, electrical stimulation, and
      duloxetine therapy, surgery remains the primary choice in managing this
      condition. Surgical options include paravaginal defect repair, the Marshall
      Marchetti-Krantz procedure, open and laparoscopic Burch urethropexy, and
      pubovaginal sling procedures. There is a growing trend in the United States
      toward use of the pubovaginal sling procedure as the primary operation for
      urinary incontinence due to less invasive techniques. Studies comparing the
      pubovaginal sling with open urethropexy have shown similar short-term cure rates.
      More large prospective, randomized studies are needed to assess long-term rates.

PMID- 16985905
TI  - Female pelvic floor anatomy: the pelvic floor, supporting structures, and pelvic
      organs.
AB  - The development of novel, less invasive therapies for stress urinary incontinence
      in women requires a thorough knowledge of the relationship between the
      pathophysiology of incontinence and anatomy. This article provides a review of
      the anatomy of the pelvic floor and lower urinary tract. Also discussed is the
      hammock hypothesis, which describes urethral support within the pelvis and
      provides an explanation of the continence mechanism.

PMID- 16985906
TI  - Sling and bulking agent placement procedures.
AB  - Sling procedures have been used for the treatment of stress urinary incontinence
      since the early 1900s. Traditional sling procedures are best performed with
      autologous rectus fascia or fascia lata, and the sling material should penetrate
      the urogenital diaphragm (perineal membrane) into the retropubic space. Tension
      free slings using polypropylene have excellent efficacy and safety data and are
      applicable in an outpatient setting. They are a good firstline surgical choice.
      Periurethral bulking agents have application for patients with a relatively
      immobile bladder neck and in cases of medical compromise or a desire for a
      simple, office-type treatment.

PMID- 16985907
TI  - Early Response Time in Sexual Activity and Mood Following Testosterone Gel
      Replacement in Hypogonadal Males from the Testim(R) START Study.
AB  - Sexual activity, sexual desire, and mood decrease in men with low testosterone
      levels. The Testim(R) Study of Testosterone Androgen Response Time (START)
      explored the time to response in sexual activity, desire, and mood following
      testosterone replacement therapy with Testim for 30 days in 638 hypogonadal men.
      Response in sexual activity, desire, and mood all improved relative to baseline
      within the first week of Testim therapy. Patients reached a maximal response by
      the end of 2 weeks of therapy and maintained the response through 4 weeks of
      therapy. Frequency of intercourse showed a significant increase after 2 weeks of
      Testim therapy. Both measures of positive mood and negative mood improved
      significantly, beginning with the first week of therapy and reaching and
      maintaining a maximal response at the second week.

PMID- 16985908
TI  - Long-term effects of testim(r) 1% testosterone gel in hypogonadal men.
AB  - A new transdermal preparation, Testim(R) 1% testosterone gel, has recently become
      available for normalization of serum testosterone in hypogonadal men. In short
      term studies, it has been shown to reverse the clinical signs and symptoms of low
      testosterone and to be well tolerated with less application-site irritation than
      with testosterone patches. In 2 long-term studies with Testim, the predose early
      morning serum testosterone (T), dihydrotestosterone (DHT), and free testosterone
      (FT) levels were assessed. Serum T, DHT, and FT were all maintained in the normal
      range for up to 12 months. In these studies, involving a total of 371 hypogonadal
      men, evaluation by means of dual-energy x-ray absorptiometry revealed a
      significant increase from baseline in bone mineral density. A significant
      improvement was also observed in body composition (increased lean body mass,
      decreased fat mass, and decreased percent fat). In addition, significant
      improvements in mood and sexual function were maintained for up to 12 months of
      treatment. The parameters measured included sexual performance, sexual
      motivation, sexual desire, and occurrence of spontaneous erections. These data
      from the 2 long-term studies support the results of the 90-day studies with
      Testim showing that the gel significantly improves the signs and symptoms
      associated with low testosterone compared with placebo. The data also support the
      conclusion that these improvements are maintained for up to 1 year of additional
      treatment.

PMID- 16985909
TI  - Diagnosis of hypogonadism: clinical assessments and laboratory tests.
AB  - Hypogonadism can be of hypothalamic-pituitary origin or of testicular origin, or
      a combination of both, which is increasingly common in the aging male population.
      In the postpubertal male, testosterone replacement therapy can be used to treat
      the signs and symptoms of low testosterone, which include loss of libido,
      erectile dysfunction, diminished intellectual capacity, depression, lethargy,
      osteoporosis, loss of muscle mass and strength, and some regression of secondary
      sexual characteristics. Before initiation of testosterone replacement therapy, an
      examination of the prostate and assessment of prostate symptoms should be
      performed, and both the hematocrit and lipid profile should be measured. Absolute
      contraindications to testosterone replacement therapy are prostate or breast
      cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone
      formulation.

PMID- 16985910
TI  - Osteopenia and male hypogonadism.
AB  - A 34-year-old male, with a history of chronic myelogenous lymphoma (CML)
      previously successfully treated 20 years earlier with chemotherapy, bone marrow
      transplants, and donor lymphocyte infusion therapy, presented with fatigue and
      low serum testosterone level. Evaluation revealed male hypogonadism from primary
      testicular failure due to prior CML therapy in addition to osteopenia. The
      patient received supplementary calcium, vitamin D, and testosterone; improvement
      in serum testosterone level was noted in 6 weeks, along with increased energy
      level and good libido and erectile function. Dual-energy x-ray absorptiometry
      (DEXA) scan showed improvement in bone status. Male hypogonadism is associated
      with increased risk for osteopenia and osteoporosis. Supplemental testosterone
      therapy, because of its direct effect and its aromatization to estrogen, can
      improve bone density in these patients.

PMID- 16985911
TI  - Testosterone replacement therapy for a man with prostate cancer.
AB  - A 52-year-old male with elevated serum prostate-specific antigen (PSA) level,
      moderate lower urinary tract symptoms (LUTS), and negative family history of
      prostate cancer is found to have adenocarcinoma of the prostate with negative
      bone scan. Following radical retropubic prostatectomy and satisfactory
      postoperative recovery, heretofore undetectable serum PSA level rose 35 months
      later. Digital rectal examination (DRE) and bone scan were negative. Adjuvant
      external beam radiation preceded by a 3-month injection of goserelin was
      initiated. Radiation was well tolerated, although the patient reported
      significant loss of libido, hot flashes, and depression warranting antidepressant
      medication. Failure to respond to this intervention led to initiation of
      supplemental testosterone; 1 month later, the patient reported significant relief
      of symptoms. The patient is currently successfully tapering use of supplemental
      testosterone in order to decrease andropause symptoms and to permit restoration
      of intrinsic testosterone.

PMID- 16985912
TI  - Treatment of erectile dysfunction in a hypogonadal male.
AB  - Anecdotal evidence suggests that hypogonadal men who failed to respond to
      sildenafil citrate changed their response when supplemented with androgens. The
      author presents the case of a middle-aged man with hypogonadism who experienced
      success with sildenafil citrate with supplemental testosterone.

PMID- 16985913
TI  - Rising PSA during Testosterone Replacement Therapy.
AB  - Although testosterone replacement therapy (TRT) is indicated for the management
      of symptomatic hypogonadism, there is still controversy over whether TRT should
      be administered to middle-aged men for the clinical manifestations of andropause,
      regardless of whether the serum testosterone levels are depressed or not. Side
      effects of TRT may include fluid retention, gynecomastia, polycythemia, and
      exacerbation of existing prostate cancer. As a result, patients on TRT require
      meticulous surveillance including regular digital rectal examination and serum
      prostate-specific antigen (PSA) testing. Herein, we present the case of a middle
      aged man with andropause and a rising PSA on TRT.

PMID- 16985914
TI  - Testosterone replacement in men with andropause: an overview.
AB  - Serum testosterone levels decline progressively as men age, with resulting
      pathophysiological changes. Because the onset of andropause is gradual and many
      of its symptoms mirror those associated with medications or disease states common
      in the elderly, a clinical diagnosis can be difficult to make. Additionally,
      because of a lack of established normal testosterone levels for different age
      groups, as well as confusion regarding what subset of testosterone to measure,
      simply testing testosterone levels is inadequate. Although clinical studies have
      shown testosterone supplementation to be safe, no long-term placebo-controlled
      trials have been performed. Among the possible side effects of testosterone
      replacement therapy is an increased risk of prostate cancer. While there is no
      evidence that supplemental testosterone will initiate prostate cancer or cause
      clinically significant progression of an established occult malignancy, the
      initial evaluation of patients prior to administration of testosterone requires
      screening for prostatic carcinoma. A number of formulations of testosterone are
      currently available; transdermal gels, although expensive, are the preferred
      modality because of their ease of administration.

PMID- 16985915
TI  - The evolving definition of advanced prostate cancer.
AB  - Each year more patients present with prostate cancer at increasingly younger ages
      and with earlier stage disease, resulting in the potential for longer survival
      time, longer-term hormonal therapy, and a heightened risk of developing
      biochemical recurrence after treatment. It seems clear that clinicians need to
      broaden the definition of "advanced" prostate cancer to include recent knowledge
      that will influence the form and timing of treatment as well as the monitoring of
      disease progression. A more contemporary definition should include patients with
      lower-grade disease and with an increased risk of progression and/or death from
      prostate cancer along with those with widely disseminated metastatic disease.
      Treatment alternatives for these patients should be evaluated based on a risk
      stratification equation toward a goal of the greatest efficacy and the least
      patient harm over time given that increasing numbers of these patients are
      entering treatment long before they develop widespread osteoblastic metastases.

PMID- 16985916
TI  - A critical review of maximal androgen blockade for advanced prostate cancer.
AB  - For over 60 years, the primary treatment for metastatic prostate cancer has been
      androgen ablation. Medical or surgical castration eliminates most, but not all
      androgen production, with a small contribution still coming from the adrenal
      gland. When castration fails, secondary adrenalectomy can provide some palliative
      benefit. However, the development of oral antiandrogens has offered an
      opportunity to simultaneously interfere with androgen produced in the testes and
      adrenal gland. Combined androgen blockade (CAB) has been investigated extensively
      with conflicting results. Based on a critical review of these studies, CAB still
      appears to offer the longest duration of survival and should continue to be
      offered as an option to men with metastatic disease.

PMID- 16985917
TI  - Neoadjuvant hormonal therapy in men being treated with radiotherapy for localized
      prostate cancer.
AB  - Several prospective randomized trials have demonstrated that men with localized
      prostate cancer benefit from the use of short-term neoadjuvant hormonal therapy
      (NHT) in combination with external beam radiotherapy (EBRT). Seven randomized
      trials were summarized in 6 publications including patients treated with NHT in
      combination with EBRT on 1 or more arms. A total of 17 different arms were
      compared including radiotherapy alone (n = 3), and NHT and concurrent hormonal
      therapy (N&CHT) (n = 12) with or without short-term adjuvant hormonal therapy
      (SAHT) (n = 5) or long-term hormonal therapy (n = 1). Patients treated with EBRT
      alone had a worse outcome than those treated with NHT. Intermediate-risk patients
      treated with 2 to 3 months of NHT did as well as those treated with longer
      neoadjuvant therapy or SAHT. The preponderance of data supports the use of NHT in
      combination with EBRT in intermediate-risk patients.

PMID- 16985918
TI  - Androgen deprivation therapy: a cornerstone in the treatment of advanced prostate
      cancer.
AB  - Decreased incidence of prostate cancer, improved therapies, and early detection
      have all have played some role in the decrease in prostate cancer mortality. The
      author discusses the development of improved methods of androgen deprivation
      therapy and demonstrates its significance in improved management of prostatic
      carcinoma.

PMID- 16985919
TI  - The changing face of urology in 2005.
AB  - The practice of urology is changing, not only from a medical and technological
      standpoint, but also from a business standpoint. New and improved computer
      technology and enhanced databases have allowed payers, including Medicare, to
      develop more detailed and complicated rules. These same advancements will allow
      physicians to streamline their practice, automate transactions, and match
      computer to computer, the continuously changing payment rules and regulations
      that determine how urologists receive payment for their services.

PMID- 16985920
TI  - 5alpha-reductase: history and clinical importance.
AB  - The treatment of men with symptomatic benign prostatic hyperplasia (BPH) has
      shifted dramatically from surgery to drug therapy over the past decade. The
      revolution in BPH treatment began with the discovery of congenital 5alpha
      reductase (5AR) deficiency, leading to the appreciation of 2 different androgenic
      hormones: testosterone, which mediates overt masculinization in the adult male,
      and dihydrotestosterone (DHT), which mediates prostatic growth, acne, facial
      beard, and male pattern baldness. Inhibition of DHT in adults results in
      prostatic shrinkage and symptomatic relief in many men, without the side effects
      seen with conventional androgen-deprivation therapy. The 5AR inhibitor drugs
      (finasteride and the dual inhibitor, dutasteride) are able to ablate the
      accumulation of intraprostatic DHT, the mechanism most responsible for prostate
      growth and maintenance. Not only may these drugs relieve symptoms, but they may
      also alter the natural history of the BPH process. Future indications for the
      5ARI drugs could include chemoprevention of prostate cancer, prophylaxis of BPH
      related complications, and treatment of BPH-associated hematuria.

PMID- 16985921
TI  - The Clinical Benefits of Dutasteride Treatment for LUTS and BPH.
AB  - Dutasteride is the first dual inhibitor of both 5alpha-reductase Types 1 and 2
      isoenzymes, with efficacy and safety proven in 3 randomized placebo-controlled
      trials, each 2 years in duration. The current report demonstrates that longer
      term treatment over 48 months with dutasteride results in continuing improvements
      in urinary symptoms and flow rate, and further reductions in total and transition
      zone volume of the prostate in men with symptomatic benign prostatic hyperplasia
      (BPH). The reduction in risk of acute urinary retention and BPH-related surgery,
      seen in the double-blind phase, was durable over the 4-year term of the studies.
      The incidence of new onset adverse events remained low during the open-label
      extension phase, and less than 1% of patients discontinued therapy due to adverse
      events. These findings combined establish that the disease-modifying benefits of
      dutasteride are durable in long-term treatment. Dutasteride was also well
      tolerated in long-term use, with no new safety issues emerging over 4 years of
      treatment.

PMID- 16985922
TI  - Pathophysiology, epidemiology, and natural history of benign prostatic
      hyperplasia.
AB  - The pathophysiology, epidemiology, and natural history of benign prostatic
      hyperplasia (BPH) are incompletely understood; however, the development of
      reliable instruments to measure symptom severity, prostatic enlargement, and
      bladder outlet obstruction has allowed major advances in their elucidation. The
      development of lower urinary tract symptoms (LUTS) in the aging male is
      influenced to some degree by the severity of bladder outlet obstruction and
      prostatic enlargement. Although the development of LUTS, bladder outlet
      obstruction, and BPH are age-dependent, they are not necessarily causally
      related; there are many other factors involved in the pathophysiology of LUTS.
      The clinically important parameters of disease progression in men with moderate
      to severe LUTS and low peak flow rates are symptom progression and the
      development of acute urinary retention (AUR). The risk of AUR is related to both
      baseline serum prostate-specific antigen level and prostate volume. In men with
      moderate prostate enlargement, the risk of AUR appears to be high enough to
      justify intervention with a 5alpha-reductase inhibitor in order to reduce this
      risk.

PMID- 16985923
TI  - Comparison of clinical trials with finasteride and dutasteride.
AB  - Finasteride selectively inhibits the Type 2 isoenzyme of 5alpha-reductase (5AR)
      (the enzyme responsible for converting testosterone to dihydrotestosterone [DHT])
      whereas dutasteride inhibits both Type 1 and Type 2 5AR. General conclusions
      regarding the differences and similarities of these 2 agents, in terms of
      pharmacologic effect, safety, and efficacy, can be drawn from evaluation of short
      term comparative trials and similar but non-comparative long-term trials.
      Dutasteride therapy reduces serum DHT significantly more than does finasteride.
      In men with benign prostatic hyperplasia (BPH), treatment with either agent
      results in similar prostate gland volume reduction, flow rate and symptom
      improvement, and similar reductions in long-term risk of BPH development in terms
      of symptom progression and acute urinary retention (AUR) and BPH-related surgery.
      There does not appear to be any clinically significant difference between the
      adverse event profiles of dutasteride and finasteride. Although weak evidence
      suggests a difference in the onset of clinical benefit, the available non
      comparative trial data do not confirm this finding. Patients with symptomatic BPH
      who receive dutasteride or finasteride, either as monotherapy or combination
      therapy with alpha-blockers, can expect to experience significant prostate gland
      size reduction, improved symptoms, and reduced risk of progression in terms of
      long-term adverse outcomes.

PMID- 16985924
TI  - The Use of Nomograms for Selecting BPH Candidates for Dutasteride Therapy.
AB  - Recent studies have discussed the benefits of medical therapy for benign
      prostatic hyperplasia (BPH), but have not provided physicians with the necessary
      tools needed to translate the information into individualized, evidence-based
      recommendations for clinically important questions. Nomograms can help physicians
      individualize their treatment decisions and predict a likely outcome by assessing
      the key risk factors for BPH progression.

PMID- 16985925
TI  - AUA Guidelines and Their Impact on the Management of BPH: An Update.
AB  - In 1994, the Benign Prostatic Hyperplasia (BPH) Guidelines Panel published
      recommendations for the diagnosis and treatment of BPH. However, numerous
      clinical studies occurring after 1994 led to the development of new medical and
      surgical therapies. Therefore, the American Urological Association published a
      more relevant set of guidelines in 2003 detailing this new information. Reviewing
      BPH literature from before and after 1994, along with unpublished data, led to
      the publication of new guidelines that reported minimally modified diagnosis
      methods as well as the updated treatment options for patients with modest to
      severe and bothersome lower urinary tract symptoms associated with BPH.

PMID- 16985926
TI  - Role of Primary Care Clinicians in the Diagnosis and Treatment of LUTS and BPH.
AB  - Primary care clinicians are often responsible for the treatment of lower urinary
      tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). The combination of
      the compelling epidemiologic presence of BPH, compromised quality of life due to
      LUTS, and the availability of highly effective oral therapeutic agents, offers an
      opportunity for substantial clinical impact in the primary care setting. Evolving
      management pathways include utilization of both symptom-modifying treatment and
      disease-modifying treatment. Alpha blockers are excellent to provide symptomatic
      treatment, but do not alter long-term disease progression. Alpha reductase
      inhibitors provide therapy by reducing the need for surgical intervention and the
      incidence of acute urinary retention. The combination of alpha blockers and alpha
      reductase inhibitors will be best for some patients, typically those with large
      prostate glands in whom disease progression is most likely. Primary care
      clinicians will want to become more familiar with recent clinical trails that are
      shaping emerging therapeutic practice.

PMID- 16985927
TI  - Overview of prostate-specific membrane antigen.
AB  - Efforts to evaluate and discover diagnostic and therapeutic markers for prostate
      cancer continue. One of these, prostate-specific membrane antigen (PSMA), a
      transmembrane protein expressed in all types of prostatic tissue, remains a
      useful diagnostic and possibly therapeutic target. The radio-immunoconjugate form
      of the anti-PSMA monoclonal antibody 7E11 is used in the commercially available
      and US Food and Drug Administration-approved diagnostic tool, the ProstaScint(R)
      (Cytogen Corporation, Princeton, NJ) scan. Recent studies have demonstrated other
      possible useful roles for PSMA as a target, not only in prostate cancer, but in
      other malignancies.

PMID- 16985928
TI  - ProstaScint(R) Scan: Contemporary Use in Clinical Practice.
AB  - Indium In 111 capromab pendetide (ProstaScint(R); Cytogen Corporation, Princeton,
      NJ), a radiolabeled monoclonal antibody to prostate-specific membrane antigen,
      offers a potential means of localizing sites of soft tissue metastasis in
      prostate cancer patients. Although the test was previously limited by poor
      positive predictive value and specificity owing to the inherent limitations of
      single photon emission computed tomography, improvements in techniques of
      anatomic localization, along with increased reader experience, have significantly
      improved its accuracy. In addition to the conventional roles for ProstaScint,
      such as staging and detection of relapse, a number of new potential applications
      have emerged.

PMID- 16985930
TI  - Overview of samarium sm 153 lexidronam in the treatment of painful metastatic
      bone disease.
AB  - Bone pain associated with advanced prostate and other cancers is a frequent and
      significant complication, and the effective management of metastatic bone disease
      and accompanying symptoms continues to be one of the major problems facing
      patients and their physicians. Treatment is in part dependent on prior
      treatments; usually a combination of systemic and local modalities is used
      because no single treatment regimen is effective for an extended period of time.
      The 3 radionuclides currently approved for treatment of bone pain (phosphorus-32,
      strontium-89, and samarium-153) are discussed in this review as viable treatment
      options, with emphasis on the third-generation agent in this category, samarium
      Sm 153 lexidronam. Clinical trial data are described that support the use of this
      agent in patients with hormone-refractory prostate cancer with painful metastatic
      bone disease, and the efficacy of and role for combination therapies are also
      discussed.

PMID- 16985931
TI  - Challenges with luteinizing hormone-releasing hormone agonists: flare and surge.
AB  - Although the mechanism behind the role of circulating androgens in the
      development and progression of prostatic carcinoma is not totally clear, androgen
      deprivation therapy remains a mainstay of treatment for this cancer. As surgical
      orchiectomy has fallen out of favor and the use of estrogens has been associated
      with cardiac toxicity, pharmacologic approaches have become even more common,
      namely, the use of luteinizing hormone-releasing hormone (LHRH) agonists. These
      agents, however, are not without side effects; the primary ones are the "flare"
      phenomenon, which stems from an initial surge in testosterone level and can
      include increased pain at metastatic sites, spinal cord compression, and even
      sudden death. Some studies have reported increased morbidity with the use of LHRH
      agonists, and while the significance of flare is not entirely known at this
      point, data seem to indicate that, at least in men with advanced disease,
      avoiding flare may be prudent.

PMID- 16985929
TI  - The future in advanced prostate cancer: take your partners or is the last dance
      for me?
AB  - Recent therapeutic initiatives have improved quality of life and survival for
      patients with advanced prostate cancer. This review focuses predominantly on
      prostate cancer that has become refractory to standard androgen ablation
      treatment. Planned trials will answer further questions on the optimal use and
      sequencing of currently available hormonal agents, cytotoxic therapies, and
      radiolabeled nucleotides. Future therapeutic advances are likely to come in 2
      areas: targeted therapies and response prediction. Molecular targeted agents will
      be most useful in combination with each other or with established systemic
      therapies. The selection of combinations will require the application of
      paradigms targeting key biochemical pathways and specific microenvironments in
      prostate cancer. Response prediction for individual patients may be assisted by
      either pretreatment or sequential molecular profiling, or sequential imaging, or
      biochemical studies that predicate outcome prior to or soon after treatment has
      been initiated. To bring these advances to the metastatic prostate cancer
      patient, a series of well-designed clinical trials is needed that integrates the
      lessons learned through laboratory, translational, and clinical studies in recent
      years.

PMID- 16985932
TI  - Downsizing and prostate cancer.
AB  - In the treatment of prostatic carcinoma, neoadjuvant androgen deprivation therapy
      has been shown to confer several clinical and quality-of-life benefits. Compared
      with the luteinizing hormone-releasing hormone agonists, gonadotropin-releasing
      hormone antagonists can achieve castrate levels of testosterone much faster,
      without the risks associated with testosterone flare. They can provide equal or
      superior efficacy in apoptosis, radiation sensitization, and prostate volume
      reduction. Urologists are increasingly employing neoadjuvant androgen deprivation
      in patients undergoing prostatectomy, radiation, brachytherapy, and cryotherapy.

PMID- 16985933
TI  - Gonadotropin-releasing hormone antagonist in the management of prostate cancer.
AB  - Luteinizing hormone-releasing hormone (LHRH) agonist therapy to induce medical
      castration has become the most common form of hormonal therapy for advanced and
      metastatic prostate cancer. When treatment is started, LHRH agonists initially
      stimulate the release of LH, causing a surge in serum testosterone that can
      precipitate a "flare" phenomenon or worsening of disease, particularly in
      patients with bone metastatic disease. Gonadotropin-releasing hormone (GnRH)
      receptor antagonism represents a newer approach to medical castration. Abarelix
      is a pure GnRH receptor antagonist that is devoid of any LHRH agonist activity.
      Results from 1 phase II and 3 phase III clinical trials demonstrate that abarelix
      produces medical castration more quickly and without causing testosterone surge,
      as compared with LHRH agonists with or without a nonsteroidal antagonist. The
      safety profile in terms of adverse events is comparable between the 2 types of
      treatment, but the lack of testosterone surge with abarelix might confer a safety
      advantage by abolishing the risk of a disease flare.

PMID- 16985934
TI  - Hormonal therapy in prostate cancer: historical approaches.
AB  - Hormonal therapy has been the standard of care for advanced prostate cancer for
      over 6 decades. Treatments to suppress testosterone have expanded beyond surgical
      castration and estrogens to include steroidal and nonsteroidal antiandrogens,
      luteinizing hormone-releasing hormone agonists, and, most recently, gonadotropin
      releasing hormone antagonists. Yet, despite this extensive therapeutic
      armamentarium, long-term survival of patients with advanced prostate cancer
      remains poor. Many issues regarding hormonal treatment of prostate cancer
      continue to be controversial, including the benefits of combined androgen
      blockade versus monotherapy, the optimal timing of treatment, and the value of
      new therapeutic approaches and strategies, such as intermittent androgen
      deprivation and adjuvant chemotherapy.

PMID- 16985935
TI  - Experimental use of GnRH antagonists as second-line hormonal therapy.
AB  - The hypothesis that follicle-stimulating hormone (FSH) signaling contributes to
      the progression of androgen-independent prostate cancer (AIPC) is supported by
      preclinical evidence. Therefore, abarelix, a gonadotropin-releasing hormone
      antagonist that suppresses circulating FSH more effectively than standard hormone
      therapies, would be expected to reduce FSH without altering testosterone, thereby
      testing the hypothesis that circulating FSH supports the progression of AIPC. The
      authors tested abarelix on 2 groups of men with early AIPC: 1 group had undergone
      luteinizing hormone-releasing hormone agonist therapy and the other had undergone
      orchiectomy. Although there was no confirmed response in either group, the
      investigators found the time to progression, fraction of patients progression
      free at the end of therapy, and fraction of patients with confirmed prostate
      specific antigen reductions less than 50% were all higher in the orchiectomy
      treated patients. This hypothesis-generating observation has led to a phase I
      trial to determine whether an escalation in the dosage of abarelix is safe and
      will produce more complete suppression of FSH.

PMID- 16985936
TI  - Case reports on prostate cancer.

PMID- 16985937
TI  - Development of an index to evaluate symptoms in men with androgen deficiency.
AB  - Healthier lifestyles and better medical care are contributing to greater life
      expectancy in U.S. males. Couple this with the great emphasis our society places
      on youth, and it is not surprising that older men want to look, feel, and act
      younger. Androgen replacement may have a role in this setting, but it is not
      clear exactly what symptoms signal a problem or warrant therapy. A valid and
      reproducible index that sufficiently defines the problems experienced by androgen
      deficient men will go a long way toward helping both researchers and clinicians
      better understand and manage these men.

PMID- 16985938
TI  - Hormone treatments and preventive strategies in the aging male: whom and when to
      treat?
AB  - Sex hormones have a broad range of actions in regulating very diverse systems
      throughout life. Testosterone and other related hormones change with age to
      varying degrees and may induce pathophysiological changes and the clinical
      condition known as andropause. Androgen replacement is the accepted but not the
      only possible treatment for andropause. The presence of clinical symptoms,
      including a loss of sexual function, intellectual capacity, lean body mass, or
      bone mineral density; alterations in body hair, skin, or sleep pattern; or
      increases in visceral fat, together with low levels of serum testosterone
      characterize andropause. An appreciation of the potentially undesirable impact of
      androgens on the biology of prostate cancer, as well as possibly the
      cardiovascular system, is necessary. However, proper evaluation of aging men with
      symptoms of andropause will result in a decision to initiate androgen therapy in
      some aging men.

PMID- 16985939
TI  - The androgen-deficient aging male: current treatment options.
AB  - All delivery forms of testosterone should be equally efficacious in treating the
      androgen-deficient aging male if adequate serum testosterone levels are obtained.
      The testosterone preparations available in North America include the oral
      undecanoate, injectable testosterone esters, the scrotal patch, the nonscrotal
      transdermal patch, and the transdermal gels. Selection of a specific testosterone
      preparation for replacement therapy depends on many factors, including the
      magnitude and pattern of serum testosterone levels produced, side effects of the
      particular formulation, reversibility if an adverse event should occur,
      convenience of use, cosmetic issues related to the preparation, and cost. In
      addition, potential adverse effects of testosterone therapy applicable to all
      forms of testosterone delivery, such as fluid retention, gynecomastia,
      polycythemia, worsening of sleep apnea, change in cardiovascular-disease risk, or
      alterations in prostate health, need to be considered both prior to therapy and
      during treatment monitoring.

PMID- 16985940
TI  - Androgen supplementation and prostate cancer risk: strategies for pretherapy
      assessment and monitoring.
AB  - Since in men androgen levels decrease with age and result in symptoms of
      hypogonadism, the use of testosterone supplementation to treat symptoms resulting
      from hypogonadism is increasing. One potential complication of this treatment is
      the possibility of an increased risk of prostate cancer. Although most
      authorities agree that androgen is involved in the exacerbation of existing
      carcinoma of the prostate, the action of androgens on the carcinogenic process is
      not well understood. Attempts to demonstrate a correlation between hormone levels
      and prostate cancer have yielded inconsistent results. No clear evidence exists
      that androgen supplementation to restore physiologic levels produces any
      deleterious effects on the prostate. It is highly doubtful that when testosterone
      therapy is administered to middle-aged or older men, any potential prostate
      cancer promotion effect will be clinically manifested in the absence of already
      established cancer. It is, however, imperative that existing or developing
      prostate cancer be ruled out before initiation and during androgen replacement
      therapy. As with any therapeutic regimen, careful monitoring of the patient
      receiving treatment is recommended and constitutes good medical care.

PMID- 16985941
TI  - Fundamental aspects of hypogonadism in the aging male.
AB  - With aging in men, serum testosterone levels decline progressively and the
      prevalence of hypogonadism increases; these changes are associated with
      alterations in androgen-regulated physiological functions. In young hypogonadal
      men, similar alterations improve with testosterone replacement. In older men,
      short-term testosterone treatment trials suggest benefits (eg, on body
      composition and bone mineral density), without significant adverse effects.
      Therefore, androgen deficiency may contribute to physiological decline with
      aging, and testosterone therapy is reasonable for older men with clinical
      manifestations of androgen deficiency and low testosterone levels. However, the
      long-term benefits and potential risks (eg, for prostate disease) of testosterone
      treatment in older men are unknown.

PMID- 16985942
TI  - New advances in the treatment of hypogonadism in the aging male.
AB  - The signs and symptoms of low testosterone in the aging male include erectile
      dysfunction, decreased libido, mood disturbances such as depression, loss of
      muscle mass, osteoporosis, and increase in body fat. Many of these signs and
      symptoms were previously believed to be part of the normal aging process, and
      only recently has treatment of low testosterone in the aging male been shown to
      provide long-term physical and mental improvement. In the past, oral and
      injectable testosterone delivery methods had disadvantages that limited their
      use, but the introduction of transdermal testosterone patches has allowed
      testosterone to be delivered into the circulation in a consistent fashion. Long
      term use of these patches over the last 3 to 10 years has been effective in
      maintaining sexual function and bone and muscle mass, and from short-term studies
      it does not appear that testosterone treatment puts men at risk for the
      development of prostate cancer. A new topical gel formation (Testim) has been
      designed to provide consistent transdermal absorption of testosterone over 24
      hours after a single dose.

PMID- 16985944
TI  - Decreased testosterone in the aging male: summary and conclusions.

PMID- 16985943
TI  - Case scenarios in androgen deficiency.
AB  - Deciding whether to choose androgen replacement for a particular patient is one
      of the many tasks facing the urologist. Factors including androgen levels,
      medical history, symptom profile, current medications, and prostate cancer risk
      all need to be considered when making this decision. However, the role each of
      these factors plays in arguing for or against androgen replacement remains
      controversial and more research is needed in many of these areas before the
      outstanding issues can be resolved. This article presents three cases involving
      patients who may require androgen supplementation. The cases describe (1) partial
      androgen deficiency syndrome, (2) testosterone deficiency in an anorchic man
      after bilateral orchiectomy for seminoma, and (3) a patient with sildenafil
      refractory erectile dysfunction following treatment of localized prostate cancer
      with radiation therapy and androgen ablation. These cases illustrate some of the
      dilemmas and controversies surrounding androgen replacement that face the
      practicing urologist.

PMID- 16985945
TI  - Docetaxel for the treatment of hormone-refractory prostate cancer.
AB  - Chemotherapy has historically proven toxic and ineffective for the treatment of
      metastatic hormone-refractory prostate cancer (HRPC), a disease with substantial
      morbidity and mortality. Progress has been made in symptom relief, and the
      combination of mitoxantrone and prednisone is considered the palliative standard
      of care. The effects of a variety of chemotherapeutic agents, both alone and in
      combination, on prostate-specific antigen decline rates, measurable disease
      response, and survival have been examined in numerous phase I and II trials.
      Results suggest that combining vinblastine or paclitaxel with estramustine
      confers a survival advantage over either agent alone. In addition, docetaxel
      based therapy has been found to be effective and well tolerated, and phase III
      trials will soon determine whether docetaxel-based therapy should replace
      mitoxantrone-based therapy as the standard of care for HRPC.

PMID- 16985946
TI  - Initial experience with single-agent docetaxel as neoadjuvant therapy in men with
      locally advanced prostate cancer.
AB  - Patients with locally advanced prostate cancer have worse outcomes after radical
      prostatectomy (RP) than patients with more favorable parameters. The findings of
      large, contemporary, RP series have led investigators at a number of centers to
      evaluate the potential role of neoadjuvant chemotherapy in patients with locally
      advanced disease. A currently ongoing study of 28 patients explores the antitumor
      response of a regimen of single-agent, docetaxel, 40 mg/m(2), administered
      intravenously on a weekly schedule for 6 weeks to patients with locally advanced
      prostate cancer before RP. Docetaxel has demonstrated significant antitumor
      activity in patients with advanced, androgen-independent disease. Study results
      showed that 75% of patients had reductions in prostate-specific antigen (PSA)
      levels ranging from 9%-79% at the completion of docetaxel therapy. In 25% of the
      patients, PSA levels increased by 2%-18% from baseline to completion of
      chemotherapy. In addition, noncastrate levels of testosterone were maintained in
      all patients. The docetaxel therapy has also been relatively well tolerated.
      Reporting of the primary endpoint of pathologic response is pending completion of
      accrual and surgery.

PMID- 16985947
TI  - Neoadjuvant Therapy for Prostate Cancer: An Oncologist's Perspective.
AB  - With increasing use of prostate-specific antigen as a screening tool, diagnosis
      of prostate cancer has undergone a stage migration toward early-stage disease.
      Although this has increased the proportion of men who are candidates for
      definitive, potentially curative therapy, it has also made clear the limitations
      of our current standard of care. Specifically, despite adequate local therapy, a
      significant proportion of men go on to develop progressive disease. Neoadjuvant
      systemic therapy is one approach that continues to be studied as a way to
      maximize cure rates in the setting of early-stage disease. This article reviews
      the current data regarding neoadjuvant therapy, both hormonal and chemotherapy,
      and discusses which men are appropriate candidates for this option.

PMID- 16985948
TI  - Biochemical (Prostate-Specific Antigen) Relapse: An Oncologist's Perspective.
AB  - Consensus has not been reached on the exact definition of biochemical relapse
      after prostatectomy; individual institution definitions of relapse after
      prostatectomy range from consecutively rising prostate-specific antigen (PSA)
      values of > 0.2 to > 0.6 ng/mL. PSA measurements after radiation are even less
      predictable. PSA level is a sensitive marker of occult prostate-cancer relapse
      and provides early notification of recurrence, but a PSA relapse does not equal a
      clinical relapse or death from prostate cancer. Data are reviewed from
      retrospective, single-institution trials that have clarified features of PSA
      relapse after both prostatectomy and radiation, such as the PSA doubling time and
      the time to the first PSA elevation, which are associated with clinical
      progression. Various options for treatment of biochemical relapse are also
      reviewed; these include hormone therapy, combined chemohormonal therapy,
      alternative medicine and dietary tactics, new agents, and future strategies, such
      as vaccination. Currently, there is no standard treatment for biochemical failure
      with proven benefit in terms of quality of life, time to metastases, or survival.
      Current options include observation for patients with long PSA doubling times or
      comorbid medical issues and standard or nontraditional hormone therapy or a
      clinical trial for men who desire early therapy or who have rapid PSA doubling
      times (< 10-12 months). Trials combining the early use of chemotherapy with
      hormone therapy are promising. Patients should be encouraged to enroll in
      clinical trials to help establish standards of care.

PMID- 16985949
TI  - A New Formulation of Calcitriol (DN-101) for High-Dose Pulse Administration in
      Prostate Cancer Therapy.
AB  - Although the antineoplastic activity of calcitriol in prostate cancer has been
      known for many years, the agent's use in oncology has been prevented because of
      the occurrence of hypercalcemia with daily administration. High-dose pulse
      administration of calcitriol has the potential to improve the therapeutic index
      of calcitriol. Results of a phase II study of calcitriol and docetaxel
      (Taxotere(R)) suggest that this combination may have utility in androgen
      independent prostate cancer (AIPC). DN-101, a high-dose (15 mug) formulation of
      calcitriol suitable for use in oncology, is now being tested in a randomized
      trial (AIPC Study of Calcitriol Enhancing Taxotere). This formulation of
      calcitriol could become an important new tool for improving the efficacy of
      docetaxel in the treatment of AIPC and would join the ranks of other nuclear
      receptor ligands in cancer treatment. Investigations of DN-101 in the treatment
      of a broad range of tumor types and in combination with a variety of agents are
      an exciting new area of research.

PMID- 16985950
TI  - Rationale for the Radiation Therapy Oncology Group Study RTOG P-0014.
AB  - Chemotherapy currently has an established role in the treatment of hormonere
      fractory prostate cancer. There is strong evidence that combined-modality
      treatment, using androgen ablation in addition to radiotherapy, provides a
      benefit above and beyond radiotherapy alone in patients with a poor prognosis,
      perhaps due to the effect of androgen ablation on subclinical distant disease.
      Several clinical trials currently under way are investigating whether the
      addition of chemotherapy with known efficacy in the hormone-refractory setting
      can provide a survival advantage when used adjuvantly.

PMID- 16985951
TI  - E-1899: An Eastern Cooperative Oncology Group Study Comparing Ketoconazole Plus
      Hydrocortisone with Docetaxel Plus Estramustine for Asymptomatic, Androgen
      Independent, Nonmetastatic Prostate Cancer Patients with Rising PSA Levels.
AB  - Many prostate cancer patients with rising prostate-specific antigen (PSA) levels
      following radical prostatectomy or radiotherapy receive "early" hormonal therapy,
      despite its uncertain benefit. When these patients ultimately progress to
      androgen independence, their management remains controversial, with many
      receiving second-line hormonal therapy. Chemotherapy for the treatment of
      advanced prostate cancer has a defined palliative benefit; studies to establish
      its potential impact on survival are ongoing. E-1899 is an intergroup phase III
      trial comparing second-line hormonal therapy with ketoconazole plus
      hydrocortisone with docetaxel plus estramustine in patients with androgen
      independent prostate cancer with rising PSA levels who have no evidence of
      metastases.

PMID- 16985952
TI  - A multi-institutional pilot study of adjuvant docetaxel for patients with
      prostate cancer at high risk for relapse after radical prostatectomy.
AB  - The management of patients with high-risk, early-stage, prostate cancer
      represents a major challenge to all disciplines involved in the treatment of this
      common malignant neoplasm. A definition of the natural history of this disease
      including the identification of key prognostic factors-and the availability of
      active systemic therapeutic modalities for patients with advanced disease are
      among the basic requirements needed to provide for early intervention in high
      risk patients. Several cytotoxic chemotherapy regimens have demonstrated
      significant antitumor effects in patients with hormone-refractory disease.
      Docetaxel (Taxotere(R), Aventis Pharmaceuticals, Bridgewater, NJ), a widely used
      taxane with broad antitumor activity, likely represents the most active single
      agent in prostate cancer treatment. Current data indicate that 40%-60% of
      patients treated with docetaxel have exhibited evidence of benefit from treatment
      with docetaxel, both alone and in combination with estramustine, with acceptable
      toxicity. In this review we describe a pilot study that is currently entering
      patients at high risk for relapse after radical prostatectomy. This study was
      designed to evaluate the safety, feasibility, and preliminary efficacy of
      docetaxel given postoperatively for 6 months. The main study endpoint is time-to
      biochemical-relapse, which will be assessed against a matched group of historical
      controls.

PMID- 16985953
TI  - Docetaxel and thalidomide as a treatment option for androgen- independent,
      nonmetastatic prostate cancer.
AB  - Prostate cancer usually presents with early-stage disease, yet a significant
      proportion of patients present or will progress to androgen-independent,
      nonmetastatic prostate cancer (AIPC). Chemotherapy has demonstrated statistically
      significant improvements in palliation of AIPC. Docetaxel in particular has
      demonstrated high response rates as a single agent. Thalidomide is effective in
      treating many malignancies, including prostate cancer. Thalidomide may act
      synergistically with docetaxel through their antiangiogenic effects. We performed
      a phase II trial of docetaxel with or without thalidomide in patients with AIPC
      and demonstrated encouraging response rates with combination therapy. We advocate
      further investigation of this promising combination regimen.

PMID- 16985954
TI  - A new paradigm for the treatment of high-risk prostate cancer: radiosensitization
      with docetaxel.
AB  - Survival and biochemical outcome of patients with localized, high-risk prostate
      cancer treated with definitive three-dimensional conformal radiation therapy (3-D
      CRT) with or without hormonal therapy are poor. Other therapeutic strategies are
      needed to improve outcome in these poor-prognostic-group patients. One such
      strategy involves the use of chemotherapeutic agents to radiosensitize the
      effects of local 3-D CRT. Very few investigators have tested this novel concept
      of chemotherapeutic radiosensitization. Two studies evaluated the combination of
      estramustine phosphate and vinblastine (EV) with radiation therapy (RT). In both
      studies, the combination of EV and RT resulted in moderate to severe acute and
      late toxicity. A recently completed, phase I trial evaluated the maximally
      tolerated dose (MTD) of weekly docetaxel that could be concurrently delivered
      with 3-D CRT (70.2 Gy) in men with high-risk prostate cancer. The MTD of
      concurrent weekly docetaxel with 3-D CRT was determined to be 20 mg/m(2), and
      this combination was shown to be safe and well tolerated. This was the first
      trial to evaluate taxane radiosensitization in prostate cancer. Other phase I/II
      studies are needed to further assess chemotherapeutic radiosensitization in
      localized, high-risk prostate cancer.

PMID- 16985955
TI  - Innovative therapies for prostate cancer treatment.
AB  - Androgen ablation is effective therapy for metastatic prostate cancer, but the
      majority of men eventually become refractory to this intervention. Cytotoxic
      chemotherapy offers palliation to symptomatic patients with hormone-refractory
      prostate cancer (HRPC); however, no chemotherapy regimen has yet been shown to
      prolong survival. There is a clear need for new agents and drug targets for the
      treatment of HRPC. A number of innovative therapeutic approaches that are
      rationally based and target driven are under investigation. This article reviews
      the development of antisense oligonucleotides that inhibit the anti-apoptotic bcL
      2 protein. Approaches that target the epidermal growth factor receptor, the
      platelet derived growth factor receptor, and nuclear factor kappa-B are also
      discussed. There is much expectation that these therapies alone or in combination
      with cytotoxic chemotherapy will impact the clinical outcome of patients with
      HRPC.

PMID- 16985956
TI  - A multidisciplinary approach to the management of hormone-refractory prostate
      cancer.
AB  - The patient with hormone-refractory prostate cancer (HRPC) presents unique
      management challenges for both the urologist and the medical oncologist. Because
      of a lack of effective treatment options, the management of patients with HRPC
      has historically been palliative. Over the past 10 years, the advent of
      relatively efficacious chemotherapeutic regimens, particularly taxane-based
      chemotherapy, has resulted in a desire to treat patients with HRPC more
      aggressively. The complex needs of these patients have made a multidisciplinary
      approach, inclusive of specialists with expertise in disease processes directly
      affecting the patient, the optimal means of treating HRPC. An understanding of
      the natural history and complications of HRPC, combined with a systemic
      evaluative process, can allow the multidisciplinary team to comprehensively
      address the needs of the individual patient with HRPC.

PMID- 16985957
TI  - CaP CURE Initiatives and Projects.
AB  - CaP CURE was founded in 1993 to help find better treatments and a cure for
      prostate cancer. By reducing the time and complexity required to apply for
      funding, and by funding many first-time applicants, CaP CURE has attracted a
      large number of high-level investigators to the field of prostate cancer
      research. The organization's Therapy Consortium meets regularly to address major
      issues that impede progress in clinical development of new treatments for
      prostate cancer. CaP CURE has also sponsored an initiative to standardize
      clinical trial design scenarios for the clinical state of rising prostate
      specific antigen and intends to present them to the Food and Drug Administration
      in partnership with the National Dialogue on Cancer. Finally, CaP CURE's efforts
      have resulted in a significant increase in federal funding of prostate cancer
      research programs.

PMID- 16985958
TI  - Benign prostatic hyperplasia: does prostate size matter?
AB  - Recent studies and analyses have confirmed that baseline prostate volume is
      related to progression of benign prostatic hyperplasia (BPH) as well as to
      negative outcomes related to BPH, such as acute urinary retention (AUR) and need
      for surgery, and can also predict response to therapy. Other investigations have
      determined that prostate-specific antigen (PSA) level has good predictive value
      for assessing prostate volume. Strong evidence exists that baseline serum PSA
      level, like baseline prostate volume, predicts future prostate growth. Randomized
      placebo-controlled finasteride trials have shown that men with larger prostate
      volumes and higher PSA levels experience a clinically significant response to
      therapy compared with those with smaller prostate volumes and lower PSA levels.
      It has also been demonstrated that men with larger prostate glands and higher PSA
      levels are at increased risk for AUR and BPH-related surgery but that finasteride
      reduces these risks. Moreover, doxazosin and finasteride, alone and in
      combination, have been shown to significantly reduce BPH clinical progression.

PMID- 16985959
TI  - 5-alpha-Reductase Inhibitors Prevent the Progression of Benign Prostatic
      Hyperplasia.
AB  - Lower urinary tract symptoms (LUTS) associated with clinical benign prostatic
      hyperplasia (BPH) are a common occurrence in aging men, causing bother and
      interference with daily activities and affecting disease-specific quality of
      life. There is increasing evidence to suggest that, in many patients, the signs
      and symptoms of BPH are progressive. Progression can be measured as continued
      growth of the prostate gland; worsening of symptoms, bother, or quality of life;
      deterioration of urinary flow rate; episodes of acute urinary retention (AUR);
      and need for prostate-related surgery. Furthermore, it has become clear that the
      risk of disease progression increases with age as well as with increasing
      prostate volume and serum prostate-specific antigen (PSA) level. The 5-alpha
      reductase inhibitor finasteride has been shown not only to improve symptoms,
      bother, and quality of life but also to prevent progression to AUR and surgery,
      with a relative risk reduction of over 50%. As the risk for such progression is
      higher in patients with larger glands or higher serum PSA values at baseline, it
      is in those patients that finasteride induces an even greater risk reduction,
      making it a cost-effective treatment choice for patients with LUTS associated
      with prostatic enlargement.

PMID- 16985960
TI  - Long-Term Experience with 5-alpha-Reductase Inhibitors.
AB  - Finasteride, a 5-alpha-reductase inhibitor, dramatically suppresses the
      production of dihydrotestosterone in men; thus, attention has turned to this
      agent for the treatment of benign prostatic hyperplasia (BPH). A number of
      randomized clinical trials have studied finasteride's effects on prostate size,
      BPH symptoms, flow rate, and prostate-specific antigen (PSA) level. Although the
      decrease in symptoms with finasteride therapy has been modest compared with more
      invasive treatments, its use has resulted in sustained reductions in prostatic
      volume and PSA level with minimal adverse effects. Fewer surgeries for BPH, as
      well as a decreased incidence of acute urinary retention, have also been seen
      with finasteride therapy. More research is needed to maximize the effectiveness
      of such medical therapy for BPH.

PMID- 16985961
TI  - Clinical evaluation of benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is the most common neoplastic condition
      afflicting men and constitutes a major factor impacting male health. Clinical
      evaluation to assess the presence and degree of voiding dysfunction and/or the
      role of BPH in its presence has an increasingly broad spectrum of treatment
      goals. The goals of the evaluation of such men are to identify the patient's
      voiding or, more appropriately, urinary tract problems, both symptomatic and
      physiologic; to establish the etiologic role of BPH in these problems; to
      evaluate the necessity for and probability of success and risks of various
      therapeutic approaches; and to present the results of these assessments to the
      patient so he can make an informed decision about management recommendations and
      available alternatives.

PMID- 16985962
TI  - Landmark studies impacting the medical management of benign prostatic
      hyperplasia.
AB  - The treatment of benign prostatic hyperplasia (BPH) has changed dramatically over
      the past 10 years. Phase 3 studies of the safety and effectiveness of alpha
      blockers (eg, terazosin and doxazosin) and 5-alpha-reductase inhibitors (eg,
      finasteride) for the treatment of BPH began to appear in the literature in 1992.
      This article reviews the results of landmark studies of these agents, either
      separately as monotherapy or as combined therapy, for the treatment of BPH. The
      relationship between prostate size and lower urinary tract symptoms (LUTS) is
      discussed. Although prostate volume is not as strongly correlated with these
      symptoms as was once believed, it has been shown to be an important predictor of
      risk for developing acute urinary retention. alpha-Blockers represent an
      effective treatment for LUTS independent of prostate volume; the clinical benefit
      of finasteride for LUTS is limited primarily to men with large prostates.
      Finasteride decreases the risk of progression to acute urinary retention and the
      requirement for surgical intervention; this benefit is greatest in men with
      enlarged prostates.

PMID- 16985964
TI  - Benign prostatic hyperplasia: case scenarios.

PMID- 16985963
TI  - The medical therapy of prostatic symptoms study: what will we learn?
AB  - Until recently, benign prostatic hyperplasia (BPH) was thought of as a relatively
      uncomplicated disease process resulting from age-related enlargement of the
      prostate gland, which was thought to cause all of the symptoms associated with
      the disease. Prostatectomy was considered the state-of-the art treatment of BPH.
      Advances in our understanding of the pathogenesis of BPH and the relationship
      among clinical signs and symptoms has allowed for the development of
      pharmacologic therapies for this disorder, namely, selective alpha-blockers and 5
      alpha-reductase inhibitors. These 2 classes of drugs have been demonstrated to be
      safe and effective for the treatment of BPH. Evidence supports different
      mechanisms of action, suggesting that, when used in combination, these therapies
      may act synergistically. The Medical Therapy of Prostatic Symptoms study was
      designed, in part, to test this hypothesis. Initial results of the trial are
      presented in this article.

PMID- 16985965
TI  - 5-alpha-Reductase Inhibitors Prevent the Progression of Benign Prostatic
      Hyperplasia.
AB  - Lower urinary tract symptoms (LUTS) associated with clinical benign prostatic
      hyperplasia (BPH) are a common occurrence in aging men, causing bother and
      interference with daily activities and affecting disease-specific quality of
      life. There is increasing evidence to suggest that, in many patients, the signs
      and symptoms of BPH are progressive. Progression can be measured as continued
      growth of the prostate gland; worsening of symptoms, bother, or quality of life;
      deterioration of urinary flow rate; episodes of acute urinary retention (AUR);
      and need for prostate-related surgery. Furthermore, it has become clear that the
      risk of disease progression increases with age as well as with increasing
      prostate volume and serum prostate-specific antigen (PSA) level. The 5-alpha
      reductase inhibitor finasteride has been shown not only to improve symptoms,
      bother, and quality of life but also to prevent progression to AUR and surgery,
      with a relative risk reduction of over 50%. As the risk for such progression is
      higher in patients with larger glands or higher serum PSA values at baseline, it
      is in those patients that finasteride induces an even greater risk reduction,
      making it a cost-effective treatment choice for patients with LUTS associated
      with prostatic enlargement.

PMID- 16985966
TI  - Long-Term Experience With 5-alpha-Reductase Inhibitors.
AB  - Finasteride, a 5-alpha-reductase inhibitor, dramatically suppresses the
      production of dihydrotestosterone in men; thus, attention has turned to this
      agent for the treatment of benign prostatic hyperplasia (BPH). A number of
      randomized clinical trials have studied finasteride's effects on prostate size,
      BPH symptoms, flow rate, and prostate-specific antigen (PSA) level. Although the
      decrease in symptoms with finasteride therapy has been modest compared with more
      invasive treatments, its use has resulted in sustained reductions in prostatic
      volume and PSA level with minimal adverse effects. Fewer surgeries for BPH, as
      well as a decreased incidence of acute urinary retention, have also been seen
      with finasteride therapy. More research is needed to maximize the effectiveness
      of such medical therapy for BPH.

PMID- 16985967
TI  - Landmark studies impacting the medical management of benign prostatic
      hyperplasia.
AB  - The treatment of benign prostatic hyperplasia (BPH) has changed dramatically over
      the past 10 years. Phase 3 studies of the safety and effectiveness of alpha
      blockers (eg, terazosin and doxazosin) and 5-alpha-reductase inhibitors (eg,
      finasteride) for the treatment of BPH began to appear in the literature in 1992.
      This article reviews the results of landmark studies of these agents, either
      separately as monotherapy or as combined therapy, for the treatment of BPH. The
      relationship between prostate size and lower urinary tract symptoms (LUTS) is
      discussed. Although prostate volume is not as strongly correlated with these
      symptoms as was once believed, it has been shown to be an important predictor of
      risk for developing acute urinary retention. alpha-Blockers represent an
      effective treatment for LUTS independent of prostate volume; the clinical benefit
      of finasteride for LUTS is limited primarily to men with large prostates.
      Finasteride decreases the risk of progression to acute urinary retention and the
      requirement for surgical intervention; this benefit is greatest in men with
      enlarged prostates.

PMID- 16985968
TI  - Clinical evaluation of benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is the most common neoplastic condition
      afflicting men and constitutes a major factor impacting male health. Clinical
      evaluation to assess the presence and degree of voiding dysfunction and/or the
      role of BPH in its presence has an increasingly broad spectrum of treatment
      goals. The goals of the evaluation of such men are to identify the patient's
      voiding or, more appropriately, urinary tract problems, both symptomatic and
      physiologic; to establish the etiologic role of BPH in these problems; to
      evaluate the necessity for and probability of success and risks of various
      therapeutic approaches; and to present the results of these assessments to the
      patient so he can make an informed decision about management recommendations and
      available alternatives.

PMID- 16985969
TI  - The medical therapy of prostatic symptoms study: what will we learn?
AB  - Until recently, benign prostatic hyperplasia (BPH) was thought of as a relatively
      uncomplicated disease process resulting from age-related enlargement of the
      prostate gland, which was thought to cause all of the symptoms associated with
      the disease. Prostatectomy was considered the state-of-the art treatment of BPH.
      Advances in our understanding of the pathogenesis of BPH and the relationship
      among clinical signs and symptoms has allowed for the development of
      pharmacologic therapies for this disorder, namely, selective alpha-blockers and 5
      alpha-reductase inhibitors. These 2 classes of drugs have been demonstrated to be
      safe and effective for the treatment of BPH. Evidence supports different
      mechanisms of action, suggesting that, when used in combination, these therapies
      may act synergistically. The Medical Therapy of Prostatic Symptoms study was
      designed, in part, to test this hypothesis. Initial results of the trial are
      presented in this article.

PMID- 16985970
TI  - A Primary Care Physician's Perspective on Benign Prostatic Hyperplasia.
AB  - Primary care clinicians are generally the first point of contact for men who
      suffer troublesome symptoms of benign prostatic hyperplasia. Although a subset of
      these patients will ultimately require referral to a urologist for an invasive
      procedure to provide symptom control, the majority can be appropriately managed
      in the ambulatory setting. Most symptomatic men respond favorably to alpha
      blockers, which provide prompt improvement in symptoms such as nocturia. Although
      alpha-blockers may control troublesome lower urinary tract symptoms, there is no
      suggestion that they forestall the need for surgery or reduce the likelihood of
      development of acute urinary retention. Therefore, clinicians need to become
      familiar with use of 5-alpha-reductase inhibitors, as this is the only class of
      pharmacotherapy that has been shown to have a diseasemodifying effect.

PMID- 16985971
TI  - Assays for complexed prostate-specific antigen and other advances in the
      diagnosis of prostate cancer.
AB  - This review discusses advances in the area of serum and tissue markers for
      prostate cancer. A recently developed assay for complexed prostate-specific
      antigen (PSA) has been found to have better specificity than that afforded by
      assay of total PSA. Researchers in Austria have found that lowering the PSA
      cutoff point for a diagnosis of prostate cancer resulted in a significant
      increase in identifying men with cancer at a favorable pathologic stage.
      Difficulties in pathologic interpretation of tissue specimens can result in both
      under- and over-diagnosis of prostate cancer. When in doubt, referral to a
      pathologist who specializes in prostate cancer is warranted. Epidermal growth
      factor receptor is emerging as an important therapeutic approach not only to
      prostate cancer but also to breast and colon cancers.

PMID- 16985972
TI  - Early diagnosis and staging of prostate cancer.
AB  - The need for accurate methods of ascertaining the malignant potential of any
      given man's prostate cancer has never been greater than it is today. The
      presenters at the session of the 13th International Prostate Cancer Update
      addressing early diagnosis and staging of disease discussed combined-modality
      staging of disease; color Doppler imaging for detection of cancer; pelvic
      lymphadenectomy as a diagnostic tool; and a new, artificial intelligence-based
      model to predict survival. A summary of these presentations is provided here.

PMID- 16985973
TI  - Complementary medicine, chemoprevention, and staging of prostate cancer.
AB  - The 13th International Prostate Cancer Update was held in Vail, Colorado, in
      February 2003. This article provides an overview of the high points in the areas
      of complementary medicine, chemoprevention, and staging that were discussed at
      this meeting. M. Scott Lucia, MD, addressed the use of various hormonal agents,
      antiproliferative or differentiating agents, antiinflammatory agents, and
      antioxidants in patients with prostate cancer. Wael A. Sakr, MD, provided an
      overview of prognostic markers for this disease. Arturo Mendoza-Valdes, MD,
      explored the potential role of exercise for patients with prostate cancer, and
      Bruce Sodee, MD, described some exciting new developments in prostate imaging. E.
      David Crawford, MD, discussed the ongoing Prostate Cancer Prevention Trial.

PMID- 16985974
TI  - Prostate cancer: epidemiology and screening.
AB  - The 13th International Prostate Cancer Update provided an overview of diagnosis,
      treatment, and management strategies in prostate cancer. This article provides a
      summary of the reports presented during the epidemiology and screening session.
      Methods to improve early detection and treatment are being developed. Proposed
      refinements to prostate-specific antigen (PSA) testing include the use of age
      specific PSA levels, PSA velocity, prostate volume-adjusted PSA densities, free
      to-total PSA ratios, and complexed PSA. Optimal follow-up screening intervals for
      persons who elect PSA testing and are found to have initially normal levels have
      been proposed. Molecular oncology is becoming increasingly important in
      understanding the development and progression of prostate cancer as well as
      identifying new therapeutic targets for hormone-refractory disease. Nomograms
      that include PSA levels, histologic grade, and the extent of the tumor have been
      developed to optimize management decisions. Despite advances in early detection
      and treatment, controversy persists because of the lack of evidence demonstrating
      that they improve length and quality of life. Until results from randomized
      trials are completed, clinicians should provide patients with balanced
      information that incorporates the potential risks and benefits of screening and
      treatment and individual preferences for various outcomes.

PMID- 16985975
TI  - Management of clinically localized prostate cancer: pathologic processing to
      robotic prostatectomy.
AB  - Prostate cancer management has undergone significant changes in recent years. The
      existing modalities are being refined, and a better understanding of pathologic
      parameters is helping in decision making. Newer sources of energy can be used to
      kill cancer cells, and modern robots are lending a helping hand in surgical
      removal of prostate cancer. The 13th International Prostate Cancer Update meeting
      provided a unique opportunity to review these recent developments. Reviewed here
      are highlights of presentations addressing recent developments in the surgical
      management of prostate cancer. The first discussion involved the processing of
      surgical specimens and interpretation of information obtained from
      histopathologic analysis. The second topic discussed here focused on an ongoing
      randomized trial comparing surgery with watchful waiting in the management of
      clinically localized prostate cancer. The last detailed presentation covered
      robotic prostatectomy and compared it with conventional open radical
      prostatectomy.

PMID- 16985976
TI  - Therapeutic strategies for localized and locally advanced prostate cancer:
      combining androgen suppression with definitive local therapy.
AB  - Patients with locally advanced prostate cancer (clinical category T3,4) managed
      with external beam radiation therapy (EBRT) and 3 years of androgen suppression
      therapy (AST) compared with patients managed with EBRT alone have been shown to
      have a survival benefit. Studies addressing the same question in patients with
      clinically localized disease (T1,2) are now completed and await follow-up. A
      decrease in positive surgical margins has been noted; however, no benefit in
      prostate-specific antigen (PSA) control has been documented in any of several
      randomized studies in which the addition of 3 months of neoadjuvant AST was
      administered before radical prostatectomy. Randomized data now show that dose
      escalated radiation provides superior PSA control rates compared with
      conventional-dose radiation therapy for patients with localized prostate cancer.
      How best to administer high-dose radiation (eg, intensity modulated radiation
      therapy, or 3-dimensional conformal radiation therapy with or without a
      brachytherapy boost), and how best to integrate high-dose radiation for patients
      with high-risk localized or locally advanced prostate cancer remain under
      investigation.

PMID- 16985977
TI  - Prostate cancer update: advanced disease.
AB  - The presentations for the "Advanced Disease" section of the 13th International
      Prostate Cancer Update provided an overview of current and future directions in
      the management of men with recurrent prostate cancer after local therapy and
      those with metastatic disease. Definitions of biochemical failure after local
      therapy were reviewed. Treatment strategies that were discussed included salvage
      radiation, early/intermittent hormonal therapy, cytotoxic chemotherapy, the use
      of bisphosphonates, and gene therapy. Several possible molecular targets for
      prostate cancer treatment need further validation before testing in clinical
      trials, and examples of these were presented. Each presentation focused on the
      need to accrue men to clinical trials to enable progress at a faster pace.

PMID- 16985978
TI  - Hormone-refractory prostate cancer: new horizons.
AB  - The eighth session of the 13th International Prostate Cancer Update focused on
      the mechanisms of androgen-independent cancer growth and on new therapeutic
      approaches to the treatment of androgen-independent prostate cancer. Three
      possible mechanisms that might account for the development of hormone resistance
      are reviewed here. These are: changes in antigen receptor expression, changes in
      androgen receptor structure, and changes in androgen receptor function.
      Therapeutic approaches discussed include the endothelin receptor antagonist
      astrasentan; PS-341, a boronic acid dipeptide that is highly selective for
      proteosome inhibition; the microtubule-stabilizing agent epothilone B; and
      exisulind, a selective apoptotic antineoplastic drug. The cooperative cancer
      study groups will move these treatments from their preliminary phase 1 and 2
      studies to comparison against the standard of care for hormone-refractory
      prostate cancer.

PMID- 16985979
TI  - Endothelial dysfunction, erectile dysfunction, and coronary heart disease: the
      pathophysiologic and clinical linkage.
AB  - Our rapidly expanding knowledge regarding the biology of the endothelial cell and
      the pathophysiology of coronary heart disease (CHD) and endothelial dysfunction
      indicates important common factors and overlapping clinical presentations. We
      are, in effect, presented with a new paradigm-that of varying vascular
      manifestations of disease linked to the functioning of endothelial cell lining.
      This article reviews these areas of advancement and addresses their clinical
      implications regarding erectile dysfunction and CHD, as well as the role of the
      phosphodiesterase-5 inhibitor sildenafil.

PMID- 16985980
TI  - Optimizing outcomes of oral therapy for patients with erectile dysfunction.
AB  - The evaluation and treatment of erectile dysfunction (ED) differs from that of
      many medical conditions. An intimate dialogue between the patient and physician
      must be established for accurate assessment of ED severity and successful
      therapy. Patient and partner education on the nuances of oral phosphodiesterase
      inhibitor therapy is important to maximize treatment success with this currently
      first-line therapy. Realistic expectations for the erectile response and patience
      are necessary to resume satisfactory sexual functioning. Relationship issues or
      partner resistance can contribute to a suboptimal erectile response to therapy,
      in which case the patient may benefit from sexual therapy referral.

PMID- 16985981
TI  - The penis as a barometer of endothelial health.
AB  - Erectile dysfunction (ED) has only within the past 25 years been recognized as
      being largely organic in cause. The introduction of phosphodiesterase-5 inhibitor
      therapy represents a major breakthrough in the treatment of ED and has resulted
      in a fast-growing body of knowledge regarding the etiology of the disorder,
      including its close association with cardiovascular disease. ED symptoms are
      often an early manifestation of endothelial dysfunction and, as such, should
      prompt further evaluation of not only the sexual dysfunction but also
      cardiovascular risk. This article discusses the importance of recognizing ED as
      much more than a quality-of-life issue.

PMID- 16985982
TI  - Asking the questions and offering solutions: the ongoing dialogue between the
      primary care physician and the patient with erectile dysfunction.
AB  - Primary care physicians are becoming more involved in inquiry about and
      management of erectile dysfunction (ED). This relatively new occurrence is
      appropriate considering that the presence of ED may signal potentially serious
      medical conditions and that ED is a condition with true morbidity. Addressing
      sexual issues in the office setting requires a comforting and secure atmosphere
      in which patients can easily discuss their problems. Because many men are
      hesitant to approach physicians with their sexual problems, clinicians need to be
      proactive by asking direct questions, either verbally or in a written history
      format. The clinician who learns of a patient's ED should acknowledge it as a
      legitimate problem and either work with the patient on a management plan or refer
      him to a physician more prepared to successfully manage the condition. Clinicians
      who choose to treat men with ED can achieve higher success rates by including the
      partner in the discussions and treatment planning and by offering some basic sex
      counseling. These efforts require additional learning on the part of the
      clinician, but the rewards of managing sexual dysfunction include happier and
      healthier patients and improved patient-partner relationships.

PMID- 16985983
TI  - Oral pharmacotherapy and the contemporary evaluation and management of erectile
      dysfunction.
AB  - The introduction of phosphodiesterase-5 (PDE-5) inhibitor therapy for the
      treatment of erectile dysfunction (ED) marked the beginning of a much greater
      awareness of this condition and its effects on quality of life. Resulting
      research has provided much data on the etiologies of ED, the risk factors
      involved, and the connection between ED and atherosclerotic disease. With the ED
      patient more frequently seeking treatment from his primary care physician, it
      behooves both urologists and non-urologist physicians to be familiar with the
      properties of the PDE-5 inhibitors, as well as those of other oral, sublingual,
      intracavernosal, and intraurethral ED drugs. This article reviews the diagnostic
      approach to the ED patient and the mechanisms of PDE-5 inhibition and discusses
      data from trials of PDE-5 inhibitors and the erectogenic dopaminergic agonist
      apomorphine.

PMID- 16985984
TI  - Treatment of the overactive bladder: where we stand in 2003.
AB  - The understanding and management of overactive bladder (OAB) continue to evolve.
      However, argument persists as to the exact incidence of the disease and the
      underlying pathophysiology of the symptom complex. Individual differences in
      symptomatic impact and, more importantly, personal coping partially account for
      the disparity noted among demographic estimates currently extant. Likewise, the
      underlying pathophysiology that leads to overt OAB syndrome is, as yet,
      incompletely characterized. Muscarinic receptor behavior provides partial
      explanation, but other complex underlying receptor and neurotransmitter
      interactions probably are also a component of the presentation. Current state-of
      the-art therapy relies on an exclusionary diagnosis prior to the inception of
      therapy. Ideally, optimal therapy involves behavioral and pharmacologic
      interventions combined to maximize therapeutic results. Antimuscarinic therapy
      provides only a degree of relief from the bothersome symptoms of OAB. As yet, few
      options exist for patients who have previously failed oral antimuscarinic
      intervention. Herein, the evolving OAB landscape will be considered as it
      currently stands in 2003. The current lack of optimal symptom control will most
      assuredly lead to the development of new pathways for OAB treatment.

PMID- 16985985
TI  - Antimuscarinic therapy for the treatment of mixed incontinence.
AB  - Mixed urinary incontinence, the combination of stress incontinence and urge
      incontinence, affects millions of Americans, significantly impacting their
      quality of life. Treatment of mixed incontinence is a therapeutic challenge, and
      the debate over whether patients are best managed initially with medication or
      surgery is ongoing. The literature supports the efficacy of both antimuscarinic
      therapy and surgery for the treatment of mixed incontinence, but patient
      selection likely influences treatment outcome. Following is a literature review
      that critically evaluates the efficacy of antimuscarinic agents for the treatment
      of mixed incontinence and addresses some of the controversial issues regarding
      surgical and pharmacologic therapy. Clinical parameters that might influence
      therapeutic outcomes and recommendations regarding treatment are also presented.

PMID- 16985986
TI  - Transdermal systems for overactive bladder: principles and practice.
AB  - The transdermal system for delivery of medication to treat overactive bladder may
      provide an improved efficacy-to-tolerability ratio by regulating serum drug
      levels; avoiding gastrointestinal and hepatic metabolism, which is important when
      the metabolite has a lesser therapeutic index than the parent drug; and achieving
      clinical efficacy with a lower total drug burden. Additional advantages may
      include increased compliance and obviation of the need for oral drug
      administration, which is especially beneficial for the patient who is taking
      multiple oral medications or is caregiver-dependent. An efficient patch system
      must preserve the physical integrity of the drug layer, provide adequate
      adhesion, store and release the drug and permeation-enhancing agent in a
      predictable manner, promote consistent absorption through the skin regardless of
      location or skin or subcutaneous tissue differences, demonstrate dose
      proportionality, maintain skin integrity during product use and removal, and be
      cosmetically acceptable. A novel transdermal delivery system that incorporates an
      occlusive layer covering an acrylic adhesive containing the active agent
      oxybutynin and a skin permeation enhancer has been demonstrated in clinical
      trials to achieve these goals.

PMID- 16985987
TI  - Neurophysiology of lower urinary tract function and dysfunction.
AB  - With the continued aging of the population, the incidence of conditions
      associated with bladder control will continue to grow. In this article, we review
      the neurophysiology and pathophysiology of the bladder and urethra and discuss
      logical concepts for the development of novel drug therapy that can better help
      the expanding population of patients with bladder control problems.

PMID- 16985988
TI  - Transdermal therapy for overactive bladder: present and future.
AB  - Transdermal delivery of certain pharmacologic agents offers distinct advantages,
      including the ability to bypass the gastrointestinal environment, fewer side
      effects, and increased bioavailability. For many patients with overactive bladder
      (OAB), transdermal therapy is more convenient than oral therapy, and the altered
      drug metabolism offers the advantages of an improved side-effect profile and
      enhanced steady-state plasma concentrations. The "newness" of transdermal
      delivery to physicians treating OAB is a potential limitation; however, much
      insight can be gained from the successful use of transdermal systems for delivery
      of other therapies, such as agents for chronic pain, hormone replacement therapy,
      and contraceptives. The transdermal oxybutynin system for OAB reduces the level
      of oxybutynin metabolites, resulting in a low incidence of anticholinergic side
      effects, and provides efficacy similar to that of standard doses of currently
      available oral preparations. However, there is room for improvement of the
      transdermal system, especially with respect to providing increased efficacy over
      currently available oral medications and reducing and treating local skin
      reactions at the application site.

PMID- 16985989
TI  - Overactive bladder in special patient populations.
AB  - It is now well accepted that overactive bladder (OAB) negatively affects the
      quality of life of a large number of persons and that the primary mode of therapy
      is the use of medication-currently antimuscarinic agents. However, it is also
      important for physicians to understand how the use of these drugs affects
      specific groups of patients. Most of the concern in this area focuses on the
      potential for these populations to experience certain adverse events or side
      effects from the use of antimuscarinic agents; this has prevented these drugs
      from being prescribed in these populations to the same degree as in the general
      population of OAB sufferers. The purpose of this article is to review these
      specific populations of OAB patients, including pediatric, geriatric, and
      pregnant patients, men with prostate problems, and patients in whom OAB is of
      neurogenic origin, and to discuss what is currently known about the use of
      antimuscarinic agents in these groups.

PMID- 16985990
TI  - Recent clinical studies of new pharmacologic agents and their efficacy in the
      treatment of incontinence.
AB  - Two agents for the control of overactive bladder-tolterodine (TOL) and extended
      release oxybutynin (Oxy-XL)-have been evaluated in a number of studies for their
      efficacy in urge incontinence. Studies have demonstrated that TOL achieved a 20%
      reduction in the frequency of voiding and a 45% reduction in urge incontinent
      episodes. Efficacy was comparable between TOL and immediate-release oxybutinin
      (Oxy-IR), the standard anticholinergic comparator. There is a delay of some weeks
      in achieving relief with TOL, but thereafter there is a continued decrease in the
      total number of both micturitions and incontinent episodes in 24 hours. Trials
      demonstrated that there were no safety concerns at all with TOL. In particular,
      there was a lower incidence of dry mouth with TOL than with Oxy-IR. Dose-ranging
      studies established that TOL produced the lowest incidence of side effects while
      maintaining efficacy. In a long-term, community-use study of Oxy-XL, there was a
      very low incidence of central nervous system side effects, including mental
      acuity and memory. Among elderly nursing home patients, Oxy-XL achieved a 90%
      reduction in weekly urge incontinence episodes and an 86% decrease in pad use.
      Oxy-XL was shown to cause a significantly lower reduction in salivary output than
      Oxy-IR and TOL. In a recent head-to-head comparison study, there were significant
      differences found between Oxy-XL and TOL. Other studies have shown that the
      administration of Oxy-XL results in a significantly lower production of the
      metabolites responsible for anticholinergic side effect, particularly dry mouth,
      than with the standard release form, owing largely to the elimination of a first
      pass effect. A long-acting form of TOL resulted in a 53% reduction in incontinent
      episodes. Both these anticholinergic agents have been shown to have excellent
      efficacy and tolerability. But the future of OAB therapy lies in targeting other
      mechanisms responsible for incontinence.

PMID- 16985991
TI  - Potential targets in the treatment of urinary incontinence.
AB  - Urgency and involuntary urine loss are distressing problems for both men and
      women. Attempts to block the primary cholinergic excitatory input to the bladder
      have led to a number of anticholinergic agents, but treatment with
      anticholinergics, the current first-line therapy, is not always effective.
      Metabolic and growth factor receptor targets are being investigated as a way to
      control the signal transduction process that leads to bladder contraction as well
      as the release of calcium that triggers this process. Because of the redundancy
      in mechanisms that promote bladder contraction, it is necessary to investigate
      multiple targets. Medical research is also focusing on purinergic receptors, the
      targeting of normally silent C-fibers that become activated due to
      neuroplasticity in the bladder, nerve-growth-factor blockade, and the blockade of
      neurotransmitters that control the bladder. Moreover, a strong correlation
      appears to exist between depression and the occurrence of incontinence, and there
      is evidence that points to a genetic link. However, the problem, with attacking
      this multiplicity of sites lies in establishing therapeutic efficacy and a high
      degree of specificity.

PMID- 16985992
TI  - The prevalence of urinary incontinence.
AB  - Urinary incontinence is a significant health problem with considerable social and
      economic impact. It is important to distinguish between prevalence and incidence
      with regard to incontinence, and prevalence-the probability of having
      incontinence within a defined population at a defined point in time-is the more
      important when considering its impact and the utilization of healthcare
      resources. There are large variations in the severity and impact of incontinence,
      and its severity, frequency, and predictability all need to be considered when
      evaluating its effects on patients, The degree of bother is particularly
      significant when determining who will need treatment. Incontinence may be a
      result of bladder dysfunction, sphincter dysfunction, or a combination of both,
      but large-scale studies are not designed to determine the etiology. In young
      women, the prevalence of incontinence is usually low, but prevalence peaks around
      menopause, with a steady rise there-after into later life. Although the
      prevalence of stress and mixed (stress and urge) incontinence is higher than urge
      incontinence, the latter is more likely to require treatment. In women, moderate
      and severe bother have a prevalence ranging from about 3% to 17%. Severe
      incontinence has a low prevalence in young women, but rapidly increases at ages
      70 through 80. In men, the prevalence of incontinence is much lower than in
      women, about 3% to 11% overall, with urge incontinence accounting for 40% to 80%
      of all male patients. Stress incontinence accounts for less than 10% of cases and
      is attributable to prostate surgery, trauma, or neurological injury. Incontinence
      in men also increases with age, but severe incontinence in 70- to 80-year-old men
      is about half of that in women. The most effective therapy for incontinence will
      rely on targeting the correct populations to be treated, which depends on how
      data is collected on prevalence and severity.

PMID- 16985993
TI  - Future trends in the treatment of urinary incontinence.
AB  - Anticholinergic drugs act on efferent nerves to counteract overactive bladder
      (OAB) after it occurs. To prevent the occurrence of OAB, therapies should be
      directed at blocking the afferent nerves that control the bladder. Tachykinin
      receptor antagonists hold great promise in this regard, since they can be
      administered orally and do not increase the risk of urinary retention that occurs
      with anticholinergics. Advanced drug delivery systems, such as controlled-release
      oral oxybutynin (oxybutynin-XL) can reduce the incidence of anticholinergic side
      effects. In a similar manner intravesical therapy for OAB is site specific, and
      thus also reduces the occurrence of adverse events. Moreover, the difficulties of
      intravesical therapy may now be overcome with advanced delivery techniques such
      as an implantable, long-acting drug-delivery pump. Another intravesical therapy
      that has met with great acceptance and success is the administration of chili
      pepper extracts, especially resiniferitoxin, which may be effective for up to 3
      months with one application. Finally, gene therapy holds great promise for OAB,
      because it is possible to access all of the genitourinary organs via endoscopy
      and other minimally invasive techniques that are ideally suited for gene therapy.

PMID- 16985994
TI  - Evaluating the effectiveness of therapies for urinary incontinence.
AB  - Subjective criteria, behavioral/emotional factors, and quality-of-life
      assessments are necessary components in evaluating incontinence therapies.
      Behavioral regimens often yield a response that lasts beyond the end of therapy
      and, when combined with pharmacologic therapy, are likely to extend duration of
      response. In addition to objective efficacy criteria, a number of instruments
      evaluate quality-of-life issues. Shortened forms of these will likely overcome
      limitations on patient compliance and completion. New instruments continue to be
      developed, but until one or more are universally accepted, variations in reported
      outcomes can be expected.

PMID- 16985995
TI  - Prostate cancer: serum and tissue markers.
AB  - The detection of prostate cancer, its clinical staging, and the prediction of its
      prognosis remain topics of paramount importance in clinical management. The
      digital rectal exam, although once the "gold standard," has been largely
      supplanted by a variety of techniques including serum and tissue-based assays.
      This article reviews recent progress in the development of prostate-specific
      antigen assays with greater specificity; molecular markers for prostate cancer
      (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion
      molecules); the link between vitamin D deficiency and the clinical emergence of
      prostate cancer; the possible correlation of serum insulin-like growth factor
      levels with the risk for developing prostate cancer; and the latest advances in
      radiologic staging.

PMID- 16985996
TI  - Prostate cancer pathology, screening, and epidemiology.
AB  - Recent advances in the understanding of prostate cancer pathology, screening
      methods, and epidemiology were discussed at the 11th International Prostate
      Cancer Update. Regarding pathology, Dr. Gary Miller enumerated several factors
      that lead to the perception of prostate cancer as "unpredictable." These include
      the disease's multifocal nature, variable progression rates, and the uncertainty
      regarding the point at which carcinomas metastasize. Screening methods have been
      the subject of research by the Laval University Prostate Cancer Screening Program
      since 1988. Dr. Fernand Labrie presented the results of this 10-year study. Dr.
      Daisaku Hirano presented data from his studies of prostate cancer epidemiology in
      Japan as compared to the United States. The role of environmental factors,
      particularly diet, in prostate cancer pathogenesis and development is supported
      by the increase of the disease in Japan, concurrent with the "westernization" of
      diet there. Finally, useful information was presented on new computer- and
      Internet-based diagnostic and research tools.

PMID- 16985998
TI  - Prostate cancer: risk assessment and diagnostic approaches.
AB  - The successful treatment of prostate cancer relies on detection of the disease at
      its earliest stages. Although prostate-specific antigen (PSA)-based screening has
      been a significant advance in the early diagnosis of prostate cancer, identifying
      specific genetic alterations in a given family or patient will allow more
      appropriate screening for early disease. Mapping and identification of specific
      prostate cancer susceptibility genes is slowly becoming a reality. Other prostate
      cancer risks include a family history, race, and possibly serum markers such as
      insulin-like growth factor-I (IGF-I). Once a high-risk man is identified,
      transrectal ultrasound (TRUS)-guided biopsies are the standard to diagnose
      prostate cancer. Although TRUS is an advance over traditional digitally directed
      biopsies, it represents a random sampling of the prostate since most lesions
      cannot be visualized. Newer modalities such as ultrasound contrast agents,
      pattern recognition, and artificial neural networks (ANNs), applied to TRUS
      images, may improve diagnostic accuracy. If a man at risk for prostate cancer has
      undergone a negative TRUS biopsy, the decision for the need for additional
      biopsies is problematic. Use of PSA derivatives such as free and total PSA and
      the initial biopsy abnormalities such as atypia or high-grade prostatic
      intraepithelial neoplasia may define those patients in need of follow-up biopsy.

PMID- 16985997
TI  - Complementary medicine for prostate cancer: effects of soy and fat consumption.
AB  - Complementary medicine has become an increasing area of interest for patients and
      researchers around the world. The utilization of some of these therapies by many
      individuals makes it imperative to understand if they have a role in cancer or
      other disease treatment. Soy products have generated a large interest because a
      variety of laboratory and epidemiologic research suggests these items may play a
      role in the prevention of prostate cancer. Clinical trials are addressing this
      issue and whether or not these products could also improve prognosis of prostate
      cancer. Additionally, other soy-based capsules (ipriflavone) have received some
      research, but the largest clinical study to date does not support the use of
      these supplements to reduce hot flashes and/or osteoporosis risk. Dietary fat
      reduction to prevent prostate cancer is supported by numerous case-control
      studies over the past 25 years. However, recent prospective studies suggest that
      fat reduction may not play a strong role in prevention of prostate carcinoma. Soy
      products and fat reduction may have a symbiotic relationship. Any healthy
      lifestyle or dietary change should be encouraged, because it may reduce the risk
      of cardiovascular disease, which is still the number one cause of mortality.

PMID- 16985999
TI  - Therapeutic strategies for localized prostate cancer.
AB  - Prostate-specific antigen determinations for prostate cancer screening have led
      to a dramatic increase in the number of men who are diagnosed with organ-confined
      and therefore potentially curable prostate cancer. Advances in predicting
      outcomes with artificial neural networks may help to recommend one therapy over
      another. Less invasive forms of treatment, such as high-intensity focused
      ultrasound, may ultimately give patients additional options for treatment.
      Furthermore, attempts to better define the role of both neoadjuvant hormonal
      therapy and chemotherapy may give higher-risk patients better outcomes than with
      current treatments. These advances as well as continued research will likely lead
      to a day when more and more men with organ-confined disease will be cured.

PMID- 16986000
TI  - Androgen deprivation and other treatments for advanced prostate cancer.
AB  - Among the issues discussed at this year's meeting on prostate cancer in Vail,
      Colorado, were several that specifically relate to the patient with advanced
      disease. Dr. E. David Crawford addressed the issue of the timing of hormone
      therapy, specifically reviewing several important trials that give a glimpse at
      the potential outcome of aggressive treatment in stage D1.5. The efficacy of
      antiandrogens, flutamide, bicalutamide, and nilutamide, when combined with
      chemical or surgical castration, was reviewed. Dr. Arturo Mendoza-Valdes reviewed
      the rationale behind intermittent (versus continuous) total androgen blockade,
      especially as related to quality of life. Dr. Paul Miller gave an update on the
      role of bisphosphonates as adjuvant therapy for prostate cancer. Also discussed
      was an important new agent for androgen deprivation, Abarelix, a sustained
      release GnRH antagonist with low histamine-releasing potential which avoids
      testosterone and other hormone surge and flare.

PMID- 16986001
TI  - New approaches to the treatment of advanced prostate cancer.
AB  - Several presentations by attendees of the 11th International Prostate Cancer
      Update addressed recent advances in prostate cancer treatment. A study that
      examined whether a relationship exists between neuroendocrine (NE) cell
      differentiation and hormone-refractory prostate cancer (HRPC) concluded that the
      appearance of NE cells in prostatic carcinoma is an important phenomenon in the
      development of HRPC. Exisuland, a selective apoptotic antineoplastic drug, was
      compared to placebo in a recent study and was found to significantly inhibit the
      increase of prostate-specific antigen in patients who had undergone radical
      prostatectomy. A new dosing regimen for flutamide (500 mg daily) was found to
      have no significant differences from the currently recommended dose (250 mg every
      8 hours); the new, single daily dose could meet with greater compliance and would
      reduce drug cost by 30%. The antiproliferative effect of vitamin D on prostatic
      carcinoma cells was discussed, along with the possible role of vitamin D
      supplementation during prostate cancer treatment. Finally, a presentation on
      hospice care acknowledged that referral for such care is unfortunately at times
      delayed by physicians, patients, and patients' families, leaving insufficient
      time for all the benefits of that stage of care to be realized.

PMID- 16986002
TI  - The evolution of hormonal therapy for prostatic carcinoma.
AB  - It is well recognized that testosterone has a number of untoward effects on
      prostatic carcinoma and that castration is associated with significant tumor
      shrinkage and resolution of symptoms of advanced prostatic carcinoma. Approaches
      to hormonal therapy have evolved significantly over the last several decades.
      Initially castration was utilized, which provided effective reduction of
      testicular androgens, but with adverse psychological factors. The next approach
      was utilization of diethylstilbestrol, but with significant cardiovascular
      toxicity in higher doses. The development of the luteinizing hormone-releasing
      hormone agonists provided an improvement in pharmacologic castration; however,
      they are associated with a transient testosterone surge and the potential for
      exacerbation of clinical manifestations of advanced prostate carcinoma (the so
      called "testosterone flare"). Recently, gonadotropin-releasing hormone (GnRH)
      antagonists have been investigated. Abarelix is a pure GnRH antagonist that
      blocks the anterior pituitary receptor, resulting in prompt and significant
      reduction not only of luteinizing hormone but also follicle-stimulating hormone.
      This results in castrate levels of testosterone while avoiding the testosterone
      surge.

PMID- 16986003
TI  - Flare Associated with LHRH-Agonist Therapy.
AB  - The most common form of hormonal treatment for prostate cancer is luteinizing
      hormone-releasing hormone (LHRH)-agonist therapy. During the first 1 to 3 weeks
      of LHRH-agonist therapy, an initial increase in testosterone is associated with a
      condition known as "flare." Blockade of flare can be accomplished with a number
      of agents, including flutamide, bicalutamide, nilutamide, diethylstilbestrol,
      ketoconazole, and cyproterone acetate. Evidence from the early use of
      LHRHagonists suggested that flare could be serious in nature, with an
      exacerbation of pain, increase in uremia, development of neurologic sequelae, and
      possibly death. These events have been uncommonly reported of late, most probably
      owing to the use of flare blockade in most patients with advanced disease, as
      well as the fact that many patients are currently being treated with much earlier
      disease. Evidence is conflicting as to whether flare makes a difference in less
      advanced disease. A few reports have noted complications during flare in patients
      in whom a blockade of flare was not required, including two deaths from one
      institution. Reported series, however, seem to suggest that with flare blockade,
      acute complications are extremely uncommon. Evidence suggests that 1) advanced
      disease should be blocked; 2) blockade should probably include an antiandrogen
      beginning about 1 week prior to administration of the LHRH-agonist; and 3) that
      patients without advanced disease but with very high PSA levels should be
      considered for flare blockade.

PMID- 16986005
TI  - Emerging pharmacologic therapies for prostate cancer.
AB  - The last decade has seen explosive growth in the therapy of prostate cancer.
      Three areas of therapeutics are emerging: 1) new compounds with novel uses; 2)
      available compounds with new applications; and 3) new compounds applied to
      established indications. The novel compounds target specific receptor sites of
      cancer pathways and attack cancer cells with less effect on normal tissue.
      Earlyphase trials with compounds targeting the endothelin-A and EGF receptors
      have shown encouraging results in hormone-refractory prostate cancer. In
      addition, the Early Prostate Cancer Trial of over 8000 men is currently underway
      to determine the benefit of adjuvant androgen ablation with bicalutamide in men
      with localized prostate cancer. Early results show a significant 42% reduction in
      the progression of the disease in the bicalutamide treatment arm. Further, in
      large, phase 3 clinical trials in patients needing androgen ablation, the GnRH
      antagonist abarelix caused no testosterone surge and demonstrated a significantly
      more rapid decline in serum testosterone to the castrate level than did an LHRH
      agonist analogue. Abarelix should thus have application as a monotherapy in
      patients who need a rapid onset of action or are at high risk of complications
      from the clinical flare seen with LHRH agonists. Abarelix also uniquely caused a
      sustained decline in serum FSH levels, which have been shown in vitro to
      stimulate prostate cancer cell growth. If these favorable effects can be
      duplicated in patients, abarelix might also offer a survival benefit.

PMID- 16986004
TI  - Basic science of hormonal therapy for prostate cancer.
AB  - New developments in molecular and cellular biology are rapidly increasing
      knowledge of the mechanisms of androgen action in the prostate. Molecular
      profiling of recurrent cancer after androgen deprivation therapy has revealed
      genetic changes related to cell survival and proliferation. It is now clear that
      loss of the androgen receptor (AR) does not explain androgen-independent growth
      of a majority of recurrent cancers. Rather, overexpression, mutation, and ligand
      independent activation of the AR may confer enhanced sensitivity to androgen or
      other growth factors. Therefore, the term "androgen-independent" is often a
      misnomer. This emerging concept is the basis of novel strategies to prevent or
      slow recurrence.

PMID- 16986006
TI  - Treatment options after failure of radiation therapy-a review.
AB  - Radioresistant or recurrent prostate cancer represents a serious health risk for
      approximately 20%-30% of patients treated with primary radiation therapy for
      clinically localized prostate cancer. The majority of patients exhibit large
      volume and poorly differentiated disease at the time of diagnosis, which limits
      the ability of salvage therapy to eradicate the cancer. Early detection with
      serum PSA monitoring and prostate needle biopsy following primary radiation
      therapy may identify residual adenocarcinoma at an earlier stage and increase the
      likelihood of successful salvage therapy. Radical prostatectomy, prostate
      cryoablation, and brachytherapy comprise the options for salvage treatment
      available for radiorecurrent prostate cancer. The goal of disease eradication
      must be balanced against the potential for serious treatment-related side
      effects. As a result, many patients receive noncurative therapy with androgen
      ablation despite the real risk of disease progression and mortality.

PMID- 16986007
TI  - Selection of salvage cryotherapy patients.
AB  - Radiation therapy is a main form of therapy for patients with localized prostate
      cancer. Despite advances in delivering radiation beams to the gland, urologists
      will be faced with managing patients with rising prostate-specific antigen values
      and radiation-recurrent cancer. If the cancer is detected early, salvage therapy
      can be initiated. Recent modifications in the technique of salvage cryosurgery
      have led to the ability to eradicate these tumors with a decrease in morbidity.
      The management and selection of these patients, as well as the results of salvage
      cryoablation, are discussed in this article.

PMID- 16986008
TI  - Radiation therapy failure in prostate cancer patients: risk factors and methods
      of detection.
AB  - Radiation therapy for clinically localized prostatic carcinoma remains one of the
      mainstays among therapeutic approaches; however, patients continue to fail
      radiation therapy at too high a rate. This article reviews the risk factors and
      methods of detection for prostate cancer recurrence. The relative merits of the
      three major pre-therapy prognostic indicators-TNM staging, Gleason score, and
      serum prostate-specific antigen (PSA) levels-are discussed. The use of staging
      and Gleason score, as well as digital rectal examination, transrectal ultrasound,
      and post-radiation prostate biopsies in detecting failure of radiation therapy is
      reviewed. Challenges relating to the use of serum PSA levels as an indicator of
      recurrence are examined. Finally, this article makes recommendations as to
      procedure for evaluating patients suspected of failing radiation therapy.

PMID- 16986009
TI  - Salvage cryosurgery-how I do it.
AB  - Prostate cryosurgery has advanced over the last decade, and is now recognized as
      a treatment option for patients who have failed radiotherapy. Appropriate patient
      selection is imperative for successful salvage. Because the treatment is a local
      therapy, the recurrent cancer must be confined to the prostate and its immediate
      area, and up to half of patients who undergo salvage cryotherapy may eventually
      fail treatment because of occult synchronous metastases. Yet some patients with
      poor prognosticators may still benefit from salvage treatment.

PMID- 16986010
TI  - Pharmacologic treatment of erectile dysfunction.
AB  - Penile erection occurs in response to cavernous smooth muscle relaxation,
      increased blood flow to the penis, and restriction of venous outflow. These
      events are regulated by a spinal reflex relying on visual, imaginative, and
      olfactory stimuli generated within the central nervous system (CNS) and on
      tactile stimuli to the penis. Drugs can have a facilitatory or inhibitory effect
      either on the nerves regulating this reflex or on the cavernous smooth muscle. A
      balance between contractile and relaxant factors governs flaccidity/rigidity
      within the penis. Drugs that raise cytosolic calcium either prevent or abort
      erection. Conversely, drugs that lower cytosolic calcium relax smooth muscle and
      can initiate penile erection. Efficacy in treating erectile dysfunction (ED) with
      phosphodiesterase inhibitors, especially type 5; alpha-adrenergic-receptor
      antagonists; and dopamine agonists exploit these mechanisms within the penis or
      CNS. Recent advances in our understanding of the pharmacology of penile erection
      are being translated into effective therapies for ED.

PMID- 16986011
TI  - Urological and medical evaluation of men with erectile dysfunction.
AB  - As the medical understanding of erectile dysfunction has evolved, the approach to
      its evaluation must also change. A good doctor/patient rapport is crucial to
      making patients more comfortable talking about their sexual function.
      Questionnaires help elicit specific information on which to base the diagnosis
      and find the etiology, along with examination of the genitals and hormone and
      other assays. If oral therapy is unsuccessful, other studies may find underlying
      conditions, leading to appropriate treatment.

PMID- 16986013
TI  - Managing concomitant cardiac disease and erectile dysfunction.
AB  - Early studies of peak heart rates and blood pressure during coitus led physicians
      to believe that sexual activity represents a significant risk to patients with
      cardiovascular disease. Subsequent studies indicated, however, that the heart
      rate during coitus was no higher than the rate during unaccustomed physical
      exercise or associated with anger. The absolute risk of myocardial infarction
      (MI) in a patient with a history of MI has been found to be 10 per million per
      hour, and the doubling of this risk in the 2 hours following coitus has a
      negligible impact on annual risk. Coronary artery disease (CAD) is a powerful
      indicator of the presence of erectile dysfunction (ED), and the risk factors for
      ED are similar to those for CAD. Studies of sildenafil citrate use in patients
      with a history of cardiovascular disease have found sildenafil to be safe and
      effective, except for an absolute contraindication in the concomitant use of
      nitrates. Physicians should become familiar with the clinical guidelines for
      classifying ED patients with a history of cardiovascular disease as high risk,
      intermediate or indeterminate risk, and low risk. The guidelines permit
      physicians MIlow risk while deferring the resumption of sexual activity among
      higher risk patients pending further evaluation.

PMID- 16986014
TI  - Future strategies for treating erectile dysfunction.
AB  - Erectile dysfunction affects over half of all men between 50 and 70 years of age,
      and by the age of 40, about 40% of men may suffer from some form of erectile
      dysfunction. Many disease states, such as diabetes, hypertension, depression, and
      vascular disease, are associated with the condition, which may occur many years
      prior to the onset of these disorders. The phenomenal success of sildenafil in
      improving erections in men with erectile dysfunction is due to the fact that the
      drug, as a phosphodiesterase inhibitor, improves the relaxation of smooth muscle
      cells, which become dysfunctional with the aging process. However, not everyone
      responds to this medication, mainly because the efficacy of the drug is directly
      dependent on the release of nitric oxide from the nerve terminals of the
      cavernosal nerve, and this may become defective with aging/certain disease
      states. The goal of gene therapy for organic impotence is to allow the patient to
      sustain physiologically elicited erections without resorting to pharmacological
      treatment immediately prior to the sexual act. Experimental efforts in gene
      therapy for erectile dysfunction are likely to continue intensively in a series
      of directions, some specific to the nature of the selected gene to be manipulated
      or the physiology of the corpora cavernosa itself, and others extrapolatable from
      the advancement of gene therapy in general.

PMID- 16986012
TI  - Four-year review of sildenafil citrate.
AB  - Within 6 months of approval by the U.S. Food and Drug Administration (FDA), 5.3
      million prescriptions were written for sildenafil citrate. It represented the
      first clearly effective and FDA-approved oral therapy for the treatment of ED.
      The chemical structure of sildenafil is very similar to the cyclic guanosine
      monophosphate molecule with which it competes, in the enzyme phosphodiesterase
      type-5. Sildenafil binds to the phosphodiesterase-5 enzyme, preventing the
      breakdown of cyclic guanosine monophosphate through competitive inhibition. The
      onset of action for sildenafil can be as short as 20 minutes and the duration of
      action may be as long as three half-lives (18 hours). Anecdotal evidence suggests
      that many men describe an erectogenic effect for almost 24 hours. The safety of
      sildenafil has been established in many pre- and postapproval studies at doses as
      high as eight times the maximum recommended dose. It is likely that the rare
      instance of myocardial infarction after taking sildenafil as directed, is due
      more to the activity of sexual intercourse rather than the medication itself.
      Efficacy have been established in patients with diabetes, parkinsonism, spinal
      cord injury, and those on antihypertensive (single- and multiple-therapy) agents.
      It has also been shown to be effective in reversing selective serotonin reuptake
      inhibitor-induced sexual side effects. Initial concerns about sildenafil with
      respect to ocular safety were based on misinterpretation of the FDA submission
      data. The two most common side effects are headache and flushing, both of which
      are short-lived and easily treated.

PMID- 16986015
TI  - The role of the primary care clinician in the management of erectile dysfunction.
AB  - Although many medical problems commonly seen in the primary care clinician's
      office are associated with ED, the majority of men do not discuss sexual
      difficulties and activities with their clinician. Patients are, however,
      appreciative of the clinician's willingness to listen and initiate discussions.
      Often a new level of patient-doctor relationship is thereby reached, which
      provides for comanagement of sexual and other disorders. The acronym "ALLOW"
      defines a 5-step proactive management plan for the primary care clinician to
      follow in order to improve his or her flexibility and sensitivity of response to
      the patient's ED; at the same time, "ALLOW" helps the clinician to recognize
      possible limitations in managing sexual health problems. More overall
      communication has been related to greater patient satisfaction, which in turn
      results in patients who are more involved in following through on their care, who
      have increased confidence in their clinician, and who continue to see one
      physician for their health care needs.

PMID- 16986016
TI  - Nonpharmacologic treatment of erectile dysfunction.
AB  - Nonpharmacologic treatment for erectile dysfunction (ED) includes sex therapy,
      the use of vacuum erection devices, penile prosthesis implantation, and penile
      vascular surgery. Sex therapy is indicated for psychogenic ED and is at times a
      useful adjunct for other treatments in men with mixed psychogenic and organic ED.
      Vacuum erection devices produce usable erections in over 90% of patients;
      however, patient and partner acceptability is an issue. Three-piece inflatable
      penile prostheses create flaccidity and an erection that comes close to that
      which occurs naturally. Penile vascular surgery has shown greatest efficacy in
      young men with vasculogenic ED resulting from pelvic or perineal trauma.

PMID- 16986017
TI  - Interventions for detrusor overactivity: the case for multimodal therapy.
AB  - Viable therapeutic alternatives for the management of overactive bladder (OAB)
      have recently evolved that provide satisfactory symptomatic control for the
      majority of patients. However, the presupposition that interventions exist as
      stand-alone entities is not representative of experience in unique populations
      with the therapeutic benefit of combination therapy, using components drawn from
      behavioral, physiotherapeutic, neuromodulatory, and, if necessary, surgical
      alternatives. Even in populations relatively refractory to therapy, the use of
      multimodal therapy yields additive benefits for patients with OAB symptoms.
      Herein is detailed the evidence supporting the concept that multimodal therapy
      provides optimal benefit to patients suffering from this symptom complex.

PMID- 16986018
TI  - Clinical impact of overactive bladder.
AB  - Overactive bladder (OAB) is a medical condition with the symptoms of urinary
      frequency and urgency, with or without urge incontinence. Traditionally,
      epidemiologic studies have focused on the symptom of incontinence, and therefore
      the prevalence and clinical impact have been grossly underestimated. Recently,
      several population-based studies have been conducted that have provided insight
      into the true magnitude of OAB. This article will review the latest data on the
      prevalence of OAB and discuss the impact of the condition on quality of life.
      Furthermore, it will examine some of the comorbidities associated with OAB and
      look at the potential economic impact of OAB.

PMID- 16986019
TI  - Selecting a medical therapy for overactive bladder.
AB  - Immediate-release oxybutynin was the gold standard for pharmacologic treatment of
      overactive bladder for nearly 30 years. Intolerable systemic side effects, in
      particular dry mouth, limited its clinical utility, resulting in poor patient
      compliance with dosing regimens. Multiple studies have demonstrated the vastly
      superior tolerability of tolterodine, extended-release tolterodine, and extended
      release oxybutynin over that of immediate-release oxybutynin at equivalent doses,
      and in the case of extended-release oxybutynin even to twice the dose of the
      original immediate-release form. With different drug delivery systems and,
      perhaps, with better bladder selectivity, these new oral agents have favorable
      side effect profiles, which translate into higher patient compliance and fewer
      treatment withdrawals or dosage reductions.

PMID- 16986020
TI  - Treatment of overactive bladder and incontinence in the elderly.
AB  - The prevalence of urinary incontinence (UI) and overactive bladder rises with
      age, and elderly people are the fastest-growing segment of the population. Many
      elderly people assume UI is a normal part of the aging process and do not report
      it to their doctors, who must therefore make the effort to elicit the information
      from them. Coexisting medical problems in older patients and the multiple
      medications many of them take make diagnosis and treatment more complex in this
      population. Just as the etiology of incontinence is often multifactorial, the
      treatment approach may need to be multipronged, with behavioral, environmental,
      and medical components; in any case, it must be targeted to the individual
      patient. New, less-invasive surgical techniques and devices make surgery more
      feasible if other therapy fails.

PMID- 16986021
TI  - The role of geriatricians and family practitioners in the treatment of overactive
      bladder and incontinence.
AB  - Although the prevalence of overactive bladder (OAB) and that of its symptoms
      (urinary urge incontinence, urgency, and frequency) increase with age, these
      conditions are not necessarily normal consequences of aging. Patients who present
      with urinary symptoms should be evaluated and treated, whether they are living on
      their own or in a residential, assisted-care, or long-term-care environment.
      Effective treatment for OAB and urinary incontinence (UI) is available and
      improves quality of life for the elderly. The primary care physician and
      geriatrician can accomplish a basic evaluation for UI using a systematic
      approach, as detailed in the following pages.

PMID- 16986022
TI  - New frontiers in the treatment of overactive bladder and incontinence.
AB  - In this article the author tries to forecast how urologists will treat the
      overactive bladder (OAB) in the next decade. He reviews drugs currently under
      development and also logical and exciting pharmacological targets that would be
      suitable targets for treating OAB in the future. The author also discusses
      intravesical therapy and alternative drug delivery methods, such as intravesical
      capsaicin and botulinum toxin. There are many advantages to advanced drug
      delivery systems, including the achievement of long-term therapeutic efficacy,
      decreased incidence and severity of side effects, and improved patient
      compliance. Special emphasis is placed on approaches to modulating bladder
      afferent nerve function to prevent OAB. Speculation on future techniques such as
      gene therapy can also be considered for treating OAB, because they may make it
      possible to access all of the genitourinary organs via minimally invasive
      techniques. Traditional anticholinergic therapies are limited in their
      effectiveness. There is great hope for future research and therapy for OAB and
      urinary incontinence.

PMID- 16986024
TI  - Pressure flow urodynamic studies: the gold standard for diagnosing bladder outlet
      obstruction.
AB  - Bladder outlet obstruction (BOO) is a common cause of lower urinary tract
      symptoms (LUTS) in men and women. By definition, BOO is determined
      urodynamically, assessing the pressure-flow relation during voiding. Since the
      1960s much work has been done to standardize the urodynamic definitions of
      obstruction in men and more recently women. Today, urodynamic testing voiding
      pressure-flow analysis remains the gold standard for the diagnosis of BOO and the
      etiology of LUTS. The pressure-flow relation is much better defined in men than
      in women, but recent work suggests that although the definition of obstruction
      may differ between men and women, the concept of the pressure-flow relation to
      diagnose obstruction holds true for both genders.

PMID- 16986023
TI  - Pathophysiology of overactive bladder and urge urinary incontinence.
AB  - Storage symptoms such as urgency, frequency, and nocturia, with or without urge
      incontinence, are characterized as overactive bladder (OAB). OAB can lead to urge
      incontinence. Disturbances in nerves, smooth muscle, and urothelium can cause
      this condition. In some respects the division between peripheral and central
      causes of OAB is artificial, but it remains a useful paradigm for appreciating
      the interactions between different tissues. Models have been developed to mimic
      the OAB associated with bladder instability, lower urinary tract obstruction,
      neuropathic disorders, diabetes, and interstitial cystitis. These models share
      the common features of increased connectivity and excitability of both detrusor
      smooth muscle and nerves. Increased excitability and connectivity of nerves
      involved in micturition rely on growth factors that orchestrate neural
      plasticity. Neurotransmitters, prostaglandins, and growth factors, such as nerve
      growth factor, provide mechanisms for bidirectional communication between muscle
      or urothelium and nerve, leading to OAB with or without urge incontinence.

PMID- 16986025
TI  - Automatic Measurement of Ultrasound-Estimated Bladder Weight (UEBW) from Three
      Dimensional Ultrasound.
AB  - Ultrasound-estimated bladder weight (UEBW) has the promise to become an important
      indicator for the diagnosis of bladder outlet obstruction. Our goal was to
      develop and evaluate an approach to accurately, consistently, conveniently, and
      noninvasively measure UEBW using three-dimensional (3D) ultrasound imaging. A 3D
      image of the bladder is acquired using a handheld ultrasound machine. The
      infravesical region of the bladder is delineated on this 3D data set to enable
      the calculation of bladder volume and the bladder surface area. The outer
      anterior wall of the bladder is delineated to enable the calculation of the
      bladder wall thickness. The UEBW is measured as a product of the bladder surface
      area, bladder wall thickness, and bladder muscle specific gravity. The UEBW was
      measured on 20 healthy male subjects and each subject was imaged several times at
      different bladder volumes to evaluate the consistency of the UEBW measurement.
      Our approach measured the average UEBW among healthy subjects to be 42 g (SD = 6
      g). The UEBW was found to be fairly consistent with an average standard deviation
      of 4 g across a single subject at different bladder volumes between 200 mL and
      400 mL. Our surface area measurements show that the bladder shape is
      significantly nonspherical.

PMID- 16986026
TI  - The relationship between pressure flow studies and ultrasound-estimated bladder
      wall mass.
AB  - The basic evaluation of suspected voiding dysfunction involves fundamental
      objective tools such as the pressure-flow study. Although accurate, the several
      drawbacks to this invasive study of bladder outlet obstruction (BOO) are
      discussed and evaluated. Other non-invasive and/or minimally invasive ways of
      diagnosing BOO continue to be the subject of investigation. The ultrasound
      estimated bladder wall thickness and bladder wall mass indices are 2 parameters
      that may be useful for screening and diagnosing BOO. Preliminary results are
      presented from the prospective clinical trial comparing the diagnosing
      capabilities and results obtained with pressure-flow studies (the historic gold
      standard for BOO diagnosing) with that of ultrasound-estimated bladder weight.

PMID- 16986027
TI  - Bladder outlet obstruction: etiology and evaluation.
AB  - Numerous gender-specific etiologies are responsible for bladder outlet
      obstruction (BOO). BOO may be induced by specific functional and anatomic causes.
      The resulting obstruction frequently produces lower urinary tract symptoms
      (LUTS). Categorizing and understanding these entities is crucial when proceeding
      with a LUTS evaluation as specific diagnostic modalities may then be used to
      fully delineate the degree of BOO and any secondary issues. Although urodynamic
      evaluation and pressure flow evaluation is the gold standard diagnostic tool,
      other modalities may also be used, including post void residual analysis, urinary
      flow rates, cystoscopy, and selected radiologic ones. Patient self-appraisal of
      symptoms using various inventories such as the American Urologic Association
      Symptom Index or the International Prostate Symptom Score is relevant to the
      initial assessment and subsequent longitudinal follow up. Analysis of secondary
      symptoms of obstruction in women is often performed using a subjective symptom
      appraisal and is determined urodynamically, assessing the pressure-flow relation
      during voiding. The complete assessment of LUTS arising from BOO often includes
      several of these modalities to fully define the obstructive impact on the
      individual's urinary function and quality of life.

PMID- 16986028
TI  - The effect of bladder outlet obstruction treatment on ultrasound-determined
      bladder wall thickness.
AB  - Detrusor hypertrophy associated with bladder outlet obstruction can be imaged on
      suprapubic ultrasound, and bladder mass can be quantified from the evaluation of
      bladder wall thickness and bladder volume. Bladder wall hypertrophy has been
      found to be correlated with detrusor function. Independent studies have shown
      that surgical treatment of benign prostatic obstruction results in a significant
      decrease of bladder mass. Preliminary data suggest the possibility that medical
      treatment with alpha-adrenergic antagonists might also produce a reduction of
      bladder wall hypertrophy, although confirmation is still awaited. The development
      of dedicated automated ultrasound systems for the evaluation of bladder mass
      might result in the use of such parameters in clinical trials of treatment for
      benign prostatic hyperplasia and ultimately in daily urologic practice.

PMID- 16986029
TI  - Treatment approaches for interstitial cystitis: multimodality therapy.
AB  - Interstitial cystitis is an increasingly common disease characterized by urgency,
      frequency, and pelvic pain. Its etiology is poorly understood but is likely to be
      multifactorial. A proposed pathophysiology describing a cascade of events,
      including epithelial dysfunction, mast cell activation, and neurogenic
      inflammation, is presented. Using this model, multimodality therapy regimens have
      been developed that treat all components of this cascade. Multimodality therapy
      appears more effective than single agents in the treatment of interstitial
      cystitis.

PMID- 16986030
TI  - The role of pentosan polysulfate in treatment approaches for interstitial
      cystitis.
AB  - Studies of the mechanisms and causes of interstitial cystitis (IC) and of the
      properties of pentosan polysulfate have provided a scientific rationale for using
      pentosan polysulfate to treat IC. In randomized, double-blind studies, patient
      and investigator evaluations of pentosan polysulfate in the treatment of IC
      resulted in favorable assessments of the drug. In addition, IC patients in two
      out of four randomized, prospective trials improved significantly in most
      variables with treatment by oral pentosan polysulfate; in the two other studies,
      the IC patients improved in some domains with pentosan therapy, although not
      significantly. Importantly, two longer-term, patient-evaluation studies showed
      that a longer duration of treatment with pentosan polysulfate resulted in greater
      improvements in patients' response rates and outcomes. The results indicate that
      treatment should be continued for 6 months or longer in order to show significant
      improvement. Of particular interest are studies suggesting that a potassium test
      may possibly predict the response of IC patients to treatment with pentosan
      polysulfate.

PMID- 16986031
TI  - Complementary and alternative therapies as treatment approaches for interstitial
      cystitis.
AB  - The management of interstitial cystitis (IC) is predominantly the reduction of
      the symptoms of frequency, urgency, and pain. Multimodal treatment approaches for
      IC are helpful in customizing therapy for individual patients. Complementary and
      alternative therapies are a quintessential addition to the therapeutic
      armamentarium and frequently include dietary modification, nutraceuticals,
      bladder training, neuromodulation, stress reduction, and sex therapy. Dietary
      modification involves elimination of bladder irritants, fluid regulation, and a
      bowel regimen. Nutraceuticals studied for the treatment of IC include calcium
      glycerophosphate, L-arginine, mucopolysaccharides, bioflavinoids, and Chinese
      herbs. Bladder training is effective after pain reduction. The neuromodulation of
      high-tone pelvic-floor muscle dysfunction is achieved with physical therapy and
      acupuncture. Stress reduction and sex therapy are best administered by a
      qualified stress manager and sex therapist. Multimodal, nonconventional
      management may add efficacy to the treatment of IC.

PMID- 16986032
TI  - Interstitial cystitis-epidemiology, diagnostic criteria, clinical markers.
AB  - Knowledge of the epidemiology of interstitial cystitis (IC), the burden of the
      disease in the population, and the identification of possible risk factors
      remains largely fragmentary. The most reliable information comes from the few
      population-based studies that have appeared in the literature over the past 25
      years, but two major issues urgently need to be addressed by appropriate
      epidemiologic studies: although studies find that only 10% of IC occurs in men,
      the hallmark symptoms of chronic prostatitis-pelvic pain, voiding dysfunction,
      and pain associated with sexual activity-overlap with those in men who carry the
      IC diagnosis. In addition, it is not known whether children suffer from the
      condition. The definition of IC is grounded in the symptomatology of pelvic pain
      and urinary frequency of a chronic nature and unexplained by any known urologic
      or other system pathology, but undue reliance on cystoscopic criteria has
      undoubtedly led to significant underdiagnosis. Efforts to identify clinical
      markers for diagnosis of IC are continuing and may lead the way to ascertaining
      the etiology and pathophysiology of IC.

PMID- 16986033
TI  - Neuromodulation for the treatment of refractory interstitial cystitis.
AB  - Interstitial cystitis (IC) is a symptom complex of urinary urgency, frequency and
      pelvic pain. Multimodality behavioral and phamacologic treatment is often
      effective in treating IC. Unfortunately, some patients with IC are refractory to
      standard treatments. Neuromodulation has been shown to be effective in treating
      voiding dysfunction. Small studies have demonstrated improvement in pelvic pain
      and IC symptoms during temporary sacral nerve stimulation. This current study
      demonstrates that patients refractory to traditional therapies for IC can respond
      well to sacral nerve stimulation and maintain improvement in symptoms after
      permanent implantation of a neurogenerator. The technique used to place the
      neurostimulator can impact on the degree of the response and the complication
      rate. Sacral neurostimulation continues to evolve and should be in the
      armamentarium available to treat voiding dysfunction.

PMID- 16986034
TI  - Economics of interstitial cystitis in clinical practice.
AB  - Urologists may be concerned that treatment of patients with interstitial cystitis
      (IC) is not economically feasible, and the time spent on these patients could be
      used for more profitable urologic therapy. However, care of IC patients can
      provide urologic practices with increased revenue opportunities through a wide
      range of procedures, including IC evaluation and management, treatment planning,
      and diagnostic, therapeutic, and even surgical techniques. Current Procedural
      Terminology (CPT) and evaluation and management (E&M) charge codes are provided
      for many types, levels, and complexities of IC procedures. Some of these
      treatments may use physician extenders who generate profits without additional
      overhead costs. Further, IC therapy may involve the use of many in-office
      services, such as urodynamics, biofeedback, and peripheral nerve stimulation that
      can be economically profitable. Rather than being an economic drain, patients
      with IC can enhance the profitability of a urologic practice while they receive
      much needed care.

PMID- 16986035
TI  - Interstitial cystitis and lower urinary tract symptoms in males and females-the
      combined role of potassium and epithelial dysfunction.
AB  - Evidence of a lower urinary tract dysfunctional epithelium has been detected in
      women and men with interstitial cystitis and other complexes of lower urinary
      tract symptoms. Lower urinary tract dysfunctional epithelium can affect the
      bladder, the urethra, the labia or vaginal introitus in women, and the prostatic
      ducts and urethra in men. Because an individual with lower urinary tract
      dysfunctional epithelium may experience pain in one or more locations throughout
      the pelvis in any combination, the clinician cannot reliably establish a
      diagnosis based on "where it hurts." A useful diagnostic tool is the intravesical
      potassium sensitivity test, which detects the abnormal epithelial permeability of
      lower urinary tract dysfunctional epithelium. In most cases, lower urinary tract
      dysfunctional epithelium can be treated successfully.

PMID- 16986036
TI  - Etiology, pathogenesis, and diagnosis of interstitial cystitis.
AB  - Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The cause
      of IC is most likely multifactorial and includes genetic and environmental
      factors. Various pathophysiological changes in the bladder, pelvis, and
      peripheral and central nervous systems have been identified, and this has led to
      the emergence of biologically specific treatment modalities. Interstitial
      cystitis is being diagnosed with increasing frequency; however, current
      diagnostic criteria are non-uniform, and there is significant overlap between
      chronic pelvic pain syndromes in men and women, interstitial cystitis, recurrent
      "cystitis," and the overactive bladder syndrome. The diagnosis of interstitial
      cystitis can be made clinically and by cystoscopy and hydrodistension. The
      sensitivity and specificity of urinary markers and the potassium sensitivity test
      have not been prospectively studied.

PMID- 16986037
TI  - Therapeutic strategies for localized prostate cancer I: surgery, ultrasound,
      adjuvant and neoadjuvant therapy.
AB  - Over the past decade, because of the introduction and widespread availability of
      prostate-specific antigen determinations, carcinoma of the prostate that is
      localized and potentially curable has been diagnosed in an increasing number of
      men. Advances in surgical management with preservation of the neurovascular
      bundles, in addition to hormone therapy, have added to the success and improved
      quality of life of patients undergoing treatment. New forms of treatment
      (including laparoscopic prostatectomy and high-intensity focused ultrasound) are
      advances that are continuing to be developed and that may have a significant role
      in the management of this disease. With further investigation and technologic
      advancement, it is anticipated that more and more men with localized disease will
      be identified and cured, with preservation of sexual and urinary function.

PMID- 16986038
TI  - Therapeutic Strategies for Localized Prostate Cancer II: Perineal Prostatectomy,
      X-Rays, Protons, Neutrons, and Combination Brachytherapy.
AB  - Application of improved imaging, diagnostic, and computer techniques is beginning
      to have an impact on the management of localized prostate cancer. It is possible
      to perform a range of surgical and radiation procedures with less morbidity than
      in the past. The changes in therapy for patients with localized disease derive
      from better knowledge of anatomy for invasive procedures and optimization of
      virtual planning for noninvasive methods. Perineal prostatectomy and combinations
      of beam and seed radiation offer both patient and physician reasonable
      therapeutic options.

PMID- 16986039
TI  - Advanced prostate cancer: an update.
AB  - A number of therapeutic options are available or on the horizon for patients for
      whom initial treatment of localized prostate cancer has failed. Currently under
      study are time of therapy, maximum androgen blockade, and palliative and
      adjunctive therapies.

PMID- 16986040
TI  - Prostate cancer: epidemiology and screening.
AB  - The challenge continues-to find better methods of screening for prostate cancer,
      of determining who should undergo needle biopsy, and of predicting who will fail
      initial therapy. Investigators are looking at the value of neural networks and an
      array of markers to provide improved screening and prognostic information.

PMID- 16986041
TI  - Docetaxel for the treatment of hormone-refractory prostate cancer.
AB  - Chemotherapy has historically proven toxic and ineffective for the treatment of
      metastatic hormone-refractory prostate cancer (HRPC), a disease with substantial
      morbidity and mortality. Progress has been made in symptom relief, and the
      combination of mitoxantrone and prednisone is considered the palliative standard
      of care. The effects of a variety of chemotherapeutic agents, both alone and in
      combination, on prostate-specific antigen decline rates, measurable disease
      response, and survival have been examined in numerous phase I and II trials.
      Results suggest that combining vinblastine or paclitaxel with estramustine
      confers a survival advantage over either agent alone. In addition, docetaxel
      based therapy has been found to be effective and well tolerated, and phase III
      trials will soon determine whether docetaxel-based therapy should replace
      mitoxantrone-based therapy as the standard of care for HRPC.

PMID- 16986042
TI  - Initial experience with single-agent docetaxel as neoadjuvant therapy in men with
      locally advanced prostate cancer.
AB  - Patients with locally advanced prostate cancer have worse outcomes after radical
      prostatectomy (RP) than patients with more favorable parameters. The findings of
      large, contemporary, RP series have led investigators at a number of centers to
      evaluate the potential role of neoadjuvant chemotherapy in patients with locally
      advanced disease. A currently ongoing study of 28 patients explores the antitumor
      response of a regimen of single-agent, docetaxel, 40 mg/m(2), administered
      intravenously on a weekly schedule for 6 weeks to patients with locally advanced
      prostate cancer before RP. Docetaxel has demonstrated significant antitumor
      activity in patients with advanced, androgen-independent disease. Study results
      showed that 75% of patients had reductions in prostate-specific antigen (PSA)
      levels ranging from 9%-79% at the completion of docetaxel therapy. In 25% of the
      patients, PSA levels increased by 2%-18% from baseline to completion of
      chemotherapy. In addition, noncastrate levels of testosterone were maintained in
      all patients. The docetaxel therapy has also been relatively well tolerated.
      Reporting of the primary endpoint of pathologic response is pending completion of
      accrual and surgery.

PMID- 16986043
TI  - Rationale for the Radiation Therapy Oncology Group Study RTOG P-0014.
AB  - Chemotherapy currently has an established role in the treatment of
      hormonerefractory prostate cancer. There is strong evidence that combined
      modality treatment, using androgen ablation in addition to radiotherapy, provides
      a benefit above and beyond radiotherapy alone in patients with a poor prognosis,
      perhaps due to the effect of androgen ablation on subclinical distant disease.
      Several clinical trials currently under way are investigating whether the
      addition of chemotherapy with known efficacy in the hormone-refractory setting
      can provide a survival advantage when used adjuvantly.

PMID- 16986044
TI  - Biochemical (Prostate-Specific Antigen) Relapse: An Oncologist's Perspective.
AB  - Consensus has not been reached on the exact definition of biochemical relapse
      after prostatectomy; individual institution definitions of relapse after
      prostatectomy range from consecutively rising prostate-specific antigen (PSA)
      values of > 0.2 to > 0.6 ng/mL. PSA measurements after radiation are even less
      predictable. PSA level is a sensitive marker of occult prostate-cancer relapse
      and provides early notification of recurrence, but a PSA relapse does not equal a
      clinical relapse or death from prostate cancer. Data are reviewed from
      retrospective, single-institution trials that have clarified features of PSA
      relapse after both prostatectomy and radiation, such as the PSA doubling time and
      the time to the first PSA elevation, which are associated with clinical
      progression. Various options for treatment of biochemical relapse are also
      reviewed; these include hormone therapy, combined chemohormonal therapy,
      alternative medicine and dietary tactics, new agents, and future strategies, such
      as vaccination. Currently, there is no standard treatment for biochemical failure
      with proven benefit in terms of quality of life, time to metastases, or survival.
      Current options include observation for patients with long PSA doubling times or
      comorbid medical issues and standard or nontraditional hormone therapy or a
      clinical trial for men who desire early therapy or who have rapid PSA doubling
      times (< 10-12 months). Trials combining the early use of chemotherapy with
      hormone therapy are promising. Patients should be encouraged to enroll in
      clinical trials to help establish standards of care.

PMID- 16986045
TI  - E-1899: An Eastern Cooperative Oncology Group Study Comparing Ketoconazole Plus
      Hydrocortisone with Docetaxel Plus Estramustine for Asymptomatic, Androgen
      Independent, Nonmetastatic Prostate Cancer Patients with Rising PSA Levels.
AB  - Many prostate cancer patients with rising prostate-specific antigen (PSA) levels
      following radical prostatectomy or radiotherapy receive "early" hormonal therapy,
      despite its uncertain benefit. When these patients ultimately progress to
      androgen independence, their management remains controversial, with many
      receiving second-line hormonal therapy. Chemotherapy for the treatment of
      advanced prostate cancer has a defined palliative benefit; studies to establish
      its potential impact on survival are ongoing. E-1899 is an intergroup phase III
      trial comparing second-line hormonal therapy with ketoconazole plus
      hydrocortisone with docetaxel plus estramustine in patients with androgen
      independent prostate cancer with rising PSA levels who have no evidence of
      metastases.

PMID- 16986046
TI  - A multi-institutional pilot study of adjuvant docetaxel for patients with
      prostate cancer at high risk for relapse after radical prostatectomy.
AB  - The management of patients with high-risk, early-stage, prostate cancer
      represents a major challenge to all disciplines involved in the treatment of this
      common malignant neoplasm. A definition of the natural history of this disease
      including the identification of key prognostic factors-and the availability of
      active systemic therapeutic modalities for patients with advanced disease are
      among the basic requirements needed to provide for early intervention in high
      risk patients. Several cytotoxic chemotherapy regimens have demonstrated
      significant antitumor effects in patients with hormone-refractory disease.
      Docetaxel (Taxotere(R), Aventis Pharmaceuticals, Bridgewater, NJ), a widely used
      taxane with broad antitumor activity, likely represents the most active single
      agent in prostate cancer treatment. Current data indicate that 40%-60% of
      patients treated with docetaxel have exhibited evidence of benefit from treatment
      with docetaxel, both alone and in combination with estramustine, with acceptable
      toxicity. In this review we describe a pilot study that is currently entering
      patients at high risk for relapse after radical prostatectomy. This study was
      designed to evaluate the safety, feasibility, and preliminary efficacy of
      docetaxel given postoperatively for 6 months. The main study endpoint is time-to
      biochemical-relapse, which will be assessed against a matched group of historical
      controls.

PMID- 16986047
TI  - The role of the urologist in treating patients with hormone-refractory prostate
      cancer.
AB  - OBJECTIVES: To ascertain what percentage of urologists' oncology practice is
      dedicated to the care of prostate cancer patients and to determine urologists'
      attitudes towards the treatment of patients with metastatic and hormone
      refractory prostate cancer (HRPC). An additional objective is to determine
      urologists' interest in administering various types of chemotherapy in HRPC
      patients. MATERIALS AND METHODS: The American Urological Association (AUA)
      directory of practicing urologists was obtained, and 3000 randomly selected
      members of the AUA, as well as the complete list of 168 Society of Urologic
      Oncology (SUO) members, were chosen for the mailing of a 16-item questionnaire.
      The urologists were asked about how many of their patients have prostate cancer,
      how many have metastatic disease, and how many have HRPC and are currently
      receiving intravenous (IV) chemotherapy. In addition, the urologists were queried
      regarding their level of interest in learning about chemotherapy options as well
      as learning how to administer chemotherapy. RESULTS: A total of 654 survey
      questionnaires were completed and returned for tabulation, resulting in a 21%
      effective response rate. Sixty-four percent of the responding urologists' cancer
      patients had prostate cancer, 21% had metastatic disease, and 19% had HRPC; only
      4% of the urologists currently administer IV chemotherapy themselves. When asked
      to describe their interest in learning how to deliver and be reimbursed for IV
      chemotherapy, 26% expressed an extremely low level of interest, 23% a low level
      of interest, 31% a high level of interest, and 17% an extremely high level of
      interest. The results of other questions are presented and correlated with the
      number of years the urologists have been in practice and other demographic data.
      CONCLUSIONS: The management of prostate cancer comprises a major portion of
      urologists' practices. Almost one half (48%) of the urologists in this survey
      were interested in administering and being reimbursed for IV chemotherapy.
      Several chemotherapy regimens have been shown to improve quality of life in
      patients with HRPC, yet only about 30% of these patients were referred for
      chemotherapy. If more urologists were able to deliver these drugs, then the
      number of patients referred for chemotherapy would likely increase, as would
      accrual to important clinical trials in HRPC. The results of this survey suggest
      that methods to implement the training and reimbursement of urologists in the use
      of chemotherapy regimens should be investigated.

PMID- 16986048
TI  - A multidisciplinary approach to the management of hormone-refractory prostate
      cancer.
AB  - The patient with hormone-refractory prostate cancer (HRPC) presents unique
      management challenges for both the urologist and the medical oncologist. Because
      of a lack of effective treatment options, the management of patients with HRPC
      has historically been palliative. Over the past 10 years, the advent of
      relatively efficacious chemotherapeutic regimens, particularly taxane-based
      chemotherapy, has resulted in a desire to treat patients with HRPC more
      aggressively. The complex needs of these patients have made a multidisciplinary
      approach, inclusive of specialists with expertise in disease processes directly
      affecting the patient, the optimal means of treating HRPC. An understanding of
      the natural history and complications of HRPC, combined with a systemic
      evaluative process, can allow the multidisciplinary team to comprehensively
      address the needs of the individual patient with HRPC.

PMID- 16986049
TI  - CaP CURE Initiatives and Projects.
AB  - CaP CURE was founded in 1993 to help find better treatments and a cure for
      prostate cancer. By reducing the time and complexity required to apply for
      funding, and by funding many first-time applicants, CaP CURE has attracted a
      large number of high-level investigators to the field of prostate cancer
      research. The organization's Therapy Consortium meets regularly to address major
      issues that impede progress in clinical development of new treatments for
      prostate cancer. CaP CURE has also sponsored an initiative to standardize
      clinical trial design scenarios for the clinical state of rising prostate
      specific antigen and intends to present them to the Food and Drug Administration
      in partnership with the National Dialogue on Cancer. Finally, CaP CURE's efforts
      have resulted in a significant increase in federal funding of prostate cancer
      research programs.

PMID- 16986050
TI  - Summary of clinical experiences with tamsulosin for the treatment of benign
      prostatic hyperplasia.
AB  - Tamsulosin, a uroselective alpha(1A)-adrenergic-receptor antagonist, has been
      shown to improve lower urinary tract symptoms associated with benign prostatic
      hyperplasia. It has a better side effect profile than earlier alpha-adrenergic
      receptor antagonists, which were initially developed as antihypertensive agents.
      Clinical trials of 1 year or longer with tamsulosin show high tolerability for
      the 0.4 mg dose and no significant interaction with other antihypertensive
      medications.

PMID- 16986051
TI  - A Comparison of Varying alpha-Blockers and Other Pharmacotherapy Options for
      Lower Urinary Tract Symptoms.
AB  - alpha(1)-Adrenoceptor antagonists are now well established as the most common
      treatment for lower urinary tract symptoms (LUTS) suggestive of bladder outflow
      obstruction associated with benign prostatic hyperplasia. Both alpha(1)
      adrenoceptor antagonists and 5alpha-reductase inhibitors are accepted treatments
      for LUTS, but with finasteride this applies only to patients with clinically
      enlarged prostates, whereas alpha(1)-adrenoceptor antagonists are considered to
      be appropriate treatment for all patients, irrespective of prostate size.
      Systematic analyses of placebo-controlled studies show that commonly used
      alpha(1)-blockers are significantly superior to placebo in improving urinary flow
      and reducing symptoms. Efficacy of alpha-blockers appears to be well maintained
      over time, and there is no evidence of tolerance or tachyphylaxis to alpha(1)
      blockade after 6-12 months' usage. Direct comparative trials show that, in the
      short term, alpha(1)-adrenoceptor antagonists are more effective than finasteride
      in reducing symptom score. For alpha(1)-adrenoceptor antagonists, the most
      commonly reported adverse effects are dizziness, asthenia, postural hypotension,
      and syncope. Alfuzosin has a more pronounced effect on blood pressure than does
      tamsulosin, especially in elderly patients. Tamsulosin is well tolerated and has
      minimal effects on blood pressure; tamsulosin 0.4 mg has the lowest potential to
      reduce blood pressure and causes less symptomatic orthostatic hypotension than
      terazosin.

PMID- 16986052
TI  - Pathophysiology of benign prostatic hyperplasia in the aging male population.
AB  - Nearly all men will develop histological benign prostatic hyperplasia by the age
      of 80, but the degree of prostatic enlargement resulting from the hyperplasia is
      highly variable. Historically, it has often been assumed that the pathophysiology
      of lower urinary tract symptoms (LUTS) in men is the result of bladder outlet
      obstruction associated with prostatic enlargement. The observation that prostatic
      enlargement, bladder outlet obstruction, and LUTS are all age-dependent has been
      interpreted to indicate that these phenomena were causally related, but there is
      insufficient evidence for this. Undoubtedly, some men' prostatic enlargement
      causes obstruction and symptoms. Based upon the available data, however, this
      subset appears to be extremely small. Because of the many urological and
      nonurological conditions that cause LUTS and age-dependent changes in bladder and
      neurological function, it is unlikely that there exists a single dominant
      etiology for the aging male population. If this is the case, then the optimal
      management of LUTS will require different and possibly combination therapies.

PMID- 16986053
TI  - Acute urinary retention: risks and management.
AB  - Acute urinary retention (AUR) secondary to benign prostatic hyperplasia has in
      the past represented an immediate indication for surgery, and today most patients
      failing to void after an attempt at catheter removal still undergo surgery. The
      concept that this disease is in fact progressive in nature is slowly being
      accepted. Descriptive and analytical epidemiological data have shown that the
      incidence rate per 1000 person-years is less variable in the community than
      previously assumed; however, the risk is cumulative and increases with advancing
      age. The risk for patients diagnosed with benign prostatic hyperplasia is
      naturally higher, and analytical epidemiology has identified several strong risk
      factors, the most important one being serum prostate-specific antigen (PSA). In
      addition, prostate volume, maximum flow rate, and symptom severity should be
      considered when counseling patients presenting with lower urinary tract symptoms
      and clinical benign prostatic hyperplasia who are considering a course of
      watchful waiting. Efforts toward primary prevention of AUR should be directed to
      patients at increased risk, ie, those who are older and have more severe
      symptoms, larger glands, and higher PSA values. Risk reduction with finasteride
      has been demonstrated, and alpha-blockers have been shown to aid patients in
      achieving spontaneous voiding after an episode of AUR.

PMID- 16986054
TI  - Long-term efficacy and safety of tamsulosin for benign prostatic hyperplasia.
AB  - The treatment approach for recent benign prostatic hyperplasia has changed since
      the recent introduction of medical therapies with evidence-based efficacy. The
      choice of treatment to achieve symptom relief must take into account factors such
      as clinical benefits, potential for morbidity, probable long-term efficacy, and
      costs. alpha(1)1-Adrenergic receptor antagonists are the primary therapy for
      patients with benign prostatic hyperplasia presenting with lower urinary tract
      symptoms and are used by 80% of physicians as the first-line agent to treat this
      common condition in the aging male. Tamsulosin has been available in the United
      States since 1997 and has demonstrated its efficacy. Of patients completing 6
      years of treatment, 80.7% demonstrated consistent positive response with
      extremely low incidence of orthostasis, the response being greatest during the
      first year and largely maintained over the following 5 years.

PMID- 16986055
TI  - Is There a Role for alpha-Blockers for the Treatment of Voiding Dysfunction
      Unrelated to Benign Prostatic Hyperplasia?
AB  - alpha-Adrenoreceptor antagonists have become the primary medical treatment for
      lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH).
      It was presumed that the primary mechanism by which alpha-blockers reduced lower
      urinary tract symptoms (LUTS) was by relaxation of smooth muscle in the prostate
      through a sympathetic response. Reduction of outlet resistance leads to changes
      in bladder function, thus improving both storage and voiding symptoms. However,
      it was observed that many patients with BPH-associated LUTS had significant
      improvement in storage symptoms without subjective or objective improvement in
      voiding. Storage symptoms associated with detrusor overactivity (frequency,
      urgency, and urge incontinence) are typically thought of as being
      parasympathetically mediated, and therefore anticholinergic medications have been
      the mainstay of pharmacological treatment, but recent work has suggested that
      several nonparasympathetic-mediated mechanisms may cause detrusor overactivity.
      Because alpha receptors appear to play a role in lower urinary tract function at
      multiple sites and levels, alpha-blockers could be used to treat voiding
      dysfunction not related to BPH. In addition, these nonprostate effects should be
      gender-independent, making the use of alpha-blockers plausible in women with
      specific types of voiding dysfunction.

PMID- 16986056
TI  - The development of lonidamine for benign prostatic hyperplasia and other
      indications.
AB  - Lonidamine (LND) is a compound originally developed as an infertility drug. By
      capitalizing on the unique energy requirements of many solid tumors including
      benign prostatic hyperplasia (BPH), LND has shown efficacy as an adjunct to
      either radiation or chemotherapy in the treatment of several advanced solid organ
      malignancies such as lung, breast, head and neck, and liver metastases. It has an
      excellent safety profile in over 20 years of use in Italy in thousands of cancer
      patients. Preliminary data suggest that it is safe and effective in the treatment
      of lower urinary tract symptoms associated with BPH by metabolically targeting
      the unique dependency of the prostate on energy production by glycolysis instead
      of the aerobe Krebs cycle. The observed effects include a fast reduction in serum
      prostate-specific antigen and prostate volume, and simultaneous improvements in
      symptoms and urinary flow rate. The fact that prostate cancer and high-grade
      prostatic intraepithelial neoplasia have similar metabolic circumstances suggests
      that LND might also be effective in various stages of the prostate cancer
      carcinogenesis.

PMID- 16986057
TI  - Lonidamine: basic science and rationale for treatment of prostatic proliferative
      disorders.
AB  - Normal and hyperplastic prostatic tissues concentrate citrate within the
      epithelium; however, a unique biochemical property within prostate epithelial
      cells renders them dependent on glycolysis, rather than the citric acid cycle,
      for energy production. Lonidamine, an orally administered small molecule that
      inhibits glycolysis by the inactivation of hexokinase, may represent a unique and
      novel approach to the treatment of benign prostatic hyperplasia (BPH). Results of
      a phase II trial of lonidamine in BPH (described elsewhere in this supplement)
      are encouraging. Lonidamine is already used in the treatment of several cancers
      in other countries. Its target-specific nature renders it a safe compound for
      administration; in cancer therapy, patients have been treated with 40 times the
      daily dose used in the BPH trial, with negligible toxicity.

PMID- 16986058
TI  - Clinical Evidence Supporting the Role of Lonidamine for the Treatment of BPH.
AB  - Glandular prostate epithelial cells of the peripheral zone are unique among
      normal cells in their dependence on glycolysis for energy production, due to a
      zinc-mediated enzymatic block in the citric acid cycle. Lonidamine (LND), a
      derivative of indazole-3-carboxylic acid, is thought to disrupt energy metabolism
      by interfering with glycolysis and to cause cell apoptosis. We evaluated the
      efficacy of oral LND treatment in subjects with symptomatic benign prostatic
      hyperplasia (BPH). The following reports the findings of an open-label study of
      orally administered LND. Thirty subjects with symptomatic BPH received oral LND
      (150 mg/day) once daily for 28 days. Subjects were assessed at baseline, at
      active-therapy assessment visits (days 14, 28), and 1, 2, 3, and 6 months post
      therapy, for prostate volume (PV) by transrectal ultrasound (TRUS), maximum flow
      rate (Q(max)) on uroflowmetry, postvoid residual urine volume (PVR),
      International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA)
      levels, serum chemistry, and adverse events.

PMID- 16986059
TI  - Pathophysiology of lower urinary tract symptoms in the aging male population.
AB  - Nearly all men will develop histological benign prostatic hyperplasia by the age
      of 80, but the degree of prostatic enlargement resulting from the hyperplasia is
      highly variable. Historically, it has often been assumed that the pathophysiology
      of lower urinary tract symptoms (LUTS) in men is the result of bladder outlet
      obstruction associated with prostatic enlargement. The observation that prostatic
      enlargement, bladder outlet obstruction, and LUTS are all age-dependent has been
      interpreted to indicate that these phenomena were causally related, but there is
      insufficient evidence for this. Undoubtedly, some men's prostatic enlargement
      causes obstruction and symptoms. Based on the available data, however, this
      subset appears to be extremely small. Because of the many urological and
      nonurological conditions that cause LUTS and age-dependent changes in bladder and
      neurological function, it is unlikely that there exists a single dominant
      etiology for the aging male population. If this is the case, then the optimal
      management of LUTS will require different and possibly combination therapies.

PMID- 16986060
TI  - Factors in Predicting Failure with Medical Therapy for BPH.
AB  - Perhaps more than other common disorders, the management of benign prostatic
      hyperplasia (BPH) has been subject to the "reatment du jour" approach. Although
      pharmacotherapy has largely replaced surgery in the treatment of BPH,
      recommendations for optimal therapy seem to change every time a new study is
      published. alpha-Blockers, 5alpha-reductase inhibitors, and combination therapy
      with the 2 have all proved highly effective, in both trials and clinical
      practice. Nevertheless, medical therapy does not work for everyone, and
      identification of baseline factors that can help predict failure with a
      particular therapy is needed. Currently, the evidence supports the use of single
      agent alpha-blocker therapy for patients with low prostate volumes at baseline,
      and combination therapy for patients with larger prostates. Symptom severity at
      baseline also seems predictive of success or failure.

PMID- 16986061
TI  - The potential for prostate cancer chemoprevention.
AB  - The dramatic international variation in prostate cancer incidence and mortality
      rates suggests that changeable environmental factors exert an influence. This has
      prompted a search for ways to prevent the disease. Epidemiologic studies suggest
      that dietary factors such as the carotenoid lycopene, selenium, vitamin E, and
      high intake of fat have roles in prostate cancer risk. Several studies show that
      impairment of androgen synthesis lowers the risk of prostate cancer. 5-alpha
      reductase inhibitors such as finasteride have been shown to decrease prostate
      size by decreasing androgenic stimulation to the prostate. Other promising, but
      less developed, interventions include vitamin D supplements and modification of
      diet. Any manipulation to decrease one's relative risk of prostate cancer will by
      necessity have to be given to a large proportion of men who would never develop
      prostate cancer even without the intervention. To be acceptable, a successful
      preventive intervention should have few or no side effects; some additional
      benefits would be useful. All potential preventive interventions will need to be
      rigorously evaluated before they can be advocated for prostate cancer prevention.

PMID- 16986062
TI  - Opportunities for prevention of prostate cancer: genetics, chemoprevention, and
      dietary intervention.
AB  - At least five susceptibility loci for the development of prostate cancer have
      been identified in the last several years. Although the specific genes involved
      have yet to be fully characterized, these discoveries hold promise for the
      identification of individuals at risk for prostate cancer years before
      development of the disease. Individuals identified as at risk through simple
      genetic screening (ie, a test on peripheral blood) could have a modified
      screening schedule, be entered into clinical trials of chemoprevention or dietary
      modification, and/or be treated according to the clinical characteristics of the
      cancer associated with a particular gene. Several large chemoprevention trials
      that exploit underlying pathogenetic mechanisms for the development of prostate
      cancer are currently underway or about to open. The future of prostate cancer is
      in the genes and our ability to manipulate the molecular events they cause.

PMID- 16986064
TI  - Risk factors for prostate cancer.
AB  - The incidence of prostate cancer in the United States has recently undergone
      dramatic and unprecedented changes. Exposure to prostate-specific antigen testing
      has led to a steep increase in reported incidence. The data indicate that the
      strongest risk factors for prostate cancer are age and African American
      race/ethnicity. Family history is also an important risk factor for prostate
      cancer, although only a small proportion of cases will be due to high-penetrance
      genes such as those at the putative susceptibility loci (eg, ELAC2) recently
      identified through linkage analysis. International variation in the risk of
      prostate cancer is profound, as is the frequency with which migrants from low- to
      high-risk areas adopt the risk pattern of the host country, possibly within a
      single generation. This article reviews the current state of knowledge regarding
      risk factors for prostate cancer, including factors related to diet,
      anthropometrics, hormone profiles, and concomitant medical conditions. The need
      for unifying, overarching hypotheses is emphasized, along with identification of
      some of the barriers to future progress in the field.

PMID- 16986063
TI  - Reducing the risk of benign prostatic hyperplasia progression.
AB  - The incidence of benign prostatic hyperplasia increases with age; the probability
      of progression rises with age at diagnosis and with baseline symptom severity.
      Although it is not life-threatening, the condition and its complications have a
      serious impact on quality of life. Acute urinary retention (AUR), though no
      longer thought an indication for immediate surgery, still requires treatment,
      often including surgery. Drug therapy with alpha-adrenergic receptor blockers or
      5-alpha-reductase inhibitors, such as finasteride, reduces the risk for AUR and
      the need for surgery, as well as symptoms and bother. Finasteride therapy also
      results in long-term reduction in prostate volume.

PMID- 16986065
TI  - Overlapping abdominal symptoms: why do GERD and IBS often coexist?
AB  - Gastroesophageal reflux disease (GERD), functional dyspepsia and irritable bowel
      syndrome (IBS) often coexist and may share a common pathophysiological mechanism.
      An association between GERD and asthma has been reported, and IBS patients have
      been shown to have an excess prevalence of bronchial hyperresponsiveness.
      Patients with overlapping IBS and dyspepsia have delayed gastric emptying rates
      as well as increased visceral hypersensitivity in both the colon and the stomach.
      Postinfectious occurrence of concomitant dyspepsia and IBS has also been
      reported, as has a familial association in functional gastrointestinal disorders.
      Although GERD, dyspepsia and IBS are highly prevalent conditions, overlapping
      symptoms should be not be attributed to their high prevalence but to a possible
      common disease process in a subset of patients.

PMID- 16986066
TI  - The complete remission concept.
AB  - The presence of esophageal lesions and gastroesophageal reflux disease (GERD)
      symptoms do not coincide in some patients: some individuals suffer from the
      symptoms of GERD but have no evidence of GERD at endoscopy; while conversely,
      some with endoscopic evidence of GERD do not experience symptoms. In order to
      combine both healing of esophageal lesions and the presence of symptoms when
      measuring treatment efficacy, the concept of complete remission has been
      redefined to include both parameters. Until recently, an effective means of
      measuring GERD symptoms and response to therapy had been lacking. The symptomatic
      reflux questionnaire ReQuest(TM) was therefore developed; it is a validated, self
      administered, hierarchical, dimension-oriented scale to assess response of a
      broad range of symptoms to treatment. It measures the frequency and intensity of
      seven symptom dimensions: acid complaints; upper abdominal complaints; lower
      abdominal complaints; nausea; sleep disturbances; other complaints; and general
      well-being (intensity only). ReQuest(TM) has recently been combined with an
      adaptation of the Los Angeles classification for endoscopic measurement of GERD,
      thus linking the assessment of symptom relief and healing of esophageal lesions.
      The new ReQuest(TM)/ LA-classification enables the detailed clinical
      characterization of GERD patients at any stage and accurate assessment of
      treatment outcome by a single global measure.

PMID- 16986067
TI  - Debate: endoscopy is unnecessary in the management of uncomplicated GERD.
AB  - The case of a 56-year-old man with recurrent retrosternal heartburn no longer
      relieved by antacids is discussed. Arguments for and against conducting endoscopy
      in this patient are presented. Initial therapy with a standard dose proton pump
      inhibitor, without endoscopy is the suggested treatment strategy. The main
      purpose of conducting an endoscopy in a patient with chronic gastrointestinal
      reflux is to detect the presence of Barrett's esophagus. However, data indicate
      that the presence of Barrett's esophagus is unrelated to symptoms and that it is
      not significantly associated with heartburn. Additionally, there is no certainty
      that survival is improved by the detection of Barrett's esophagus. Nonetheless,
      many clinical practice guidelines support conducting endoscopy in patients with
      GERD.

PMID- 16986068
TI  - Long-term GERD management: the individualized approach.
AB  - Gastroesophageal reflux disease (GERD) is a complex condition, and both mucosal
      lesions and symptoms are important parameters in evaluating disease severity and
      the impact of treatment. An individualized approach in which treatment is
      tailored to each patient is the appropriate strategy. Treatment with a standard
      dose of a proton pump inhibitor (PPI) should be continued until symptoms resolve
      in the case of nonerosive reflux disease (NERD), or until complete remission is
      achieved (resolution of symptoms and endoscopically confirmed healing) in
      patients with erosive disease. Maintenance treatment with a half-dose PPI is
      effective in both erosive esophagitis and NERD. If NERD patients remain in
      remission with the half-dose PPI, therapy can continue in an on-demand basis. A
      relapse of symptoms often needs to be treated by a return to a full-dose PPI.
      Studies of long-term treatment with PPIs show that they are a safe and effective
      means of maintaining remission in patients with GERD.

PMID- 16986069
TI  - Application of ionic liquids to the electrodeposition of metals.
AB  - The electrodeposition of most of technologically important metals has been shown
      to be possible from a wide range of room temperature molten salts, more commonly
      known today as 'ionic liquids'. These liquids are currently under intense
      scrutiny for a wide variety of applications some of which have already been
      commercialized. Despite the fact that electrodeposition was the first application
      studied in these liquids no metal deposition processes have as yet been developed
      to an industrial scale. This review addresses the practical and theoretical
      aspects that need to be considered when choosing ionic liquids for metal
      deposition. It details the current understanding of the physical and chemical
      properties of these interesting fluids and highlights the areas that need to be
      considered to develop practical electroplating systems. The effect of composition
      and temperature on viscosity and conductivity are discussed together with the
      fundamental approaches required to synthesise new liquids.

PMID- 16986070
TI  - Optical detection of singlet oxygen from single cells.
AB  - The lowest excited electronic state of molecular oxygen, singlet molecular
      oxygen, O(2)(a (1)Delta(g)), is a reactive species involved in many chemical and
      biological processes. To better understand the roles played by singlet oxygen in
      biological systems, particularly at the sub-cellular level, optical tools have
      been developed to create and directly detect this transient state in time- and
      spatially-resolved experiments from single cells. Data obtained indicate that,
      contrary to common perception, this reactive species can be quite long-lived in a
      cell and, as such, can diffuse over appreciable distances including across the
      cell membrane into the extracellular environment. On one hand, these results
      demonstrate that the behavior of singlet oxygen in an intact cell can be
      significantly different from that inferred from model bulk studies. More
      generally, these results provide a new perspective for mechanistic studies of
      intra- and inter-cellular signaling and events that ultimately lead to photo
      induced cell death.

PMID- 16986071
TI  - First steps towards dissolution of NaSO4- by water.
AB  - NaSO(4)(-)(H(2)O)(n) (n = 0-4) clusters have been generated in the gas phase as
      model systems to simulate the first dissolution steps of sulfate salts in water;
      photoelectron spectroscopy and theoretical calculations indicate that the first
      three water molecules strongly interact with both Na(+) and SO(4)(2-), forming a
      three-water solvation ring to start to pry apart the Na(+)SO(4)(2-) contact ion
      pair.

PMID- 16986072
TI  - An FT-IRRAS study of nitrophenyl mono- and multilayers electro-deposited on gold
      by reduction of the diazonium salt.
AB  - Formation of an organometallic junction by direct bonding of 4-nitrobenzene
      monolayer on gold surface by diazonium chemistry has been demonstrated by Fourier
      transform reflection-absorption spectroscopy with s- and p-polarized radiation.

PMID- 16986073
TI  - Time dependent density functional investigation of the near-edge absorption
      spectra of V2O5.
AB  - We have performed Time Dependent Density Functional Theory (TDDFT) calculations
      employing a cluster model of the core excitation spectra of vanadium pentoxide,
      V(2)O(5). The excitation energies and dipole transition moments are determined
      for all the core edges, vanadium and oxygen K- and vanadium L-edges, treating
      them at the same level of accuracy. The agreement between the TDDFT theoretical
      spectra and the experimental data is rather good, particularly at the V and O K
      edges. A quantitative reproduction of the fine pre-edge structures appears more
      difficult for the V L-edge. The comparison between the TDDFT results and the
      results obtained at the simpler one electron Kohn-Sham (KS) level indicates that
      the V and O K edges can be correctly described within a single particle
      approximation (KS), while the strong modification of the V L-edge structures from
      the KS to the TDDFT description emphasizes the importance of configuration mixing
      to treat the metal 2p excitations. The origin of the calculated pre-edge features
      is analyzed in detail with the help of the atom-projected density-of-states of
      the unoccupied levels. This analysis emphasizes the V 3d dominant character of
      the final states in the conduction band, probed by the V L-absorption. The strong
      octahedral distortion of the V(2)O(5) structure allows the mixing of the 3d state
      with the V 4p components, which are mapped by the oscillator strength in the V K
      edge spectrum. The high intensity of the O 1s transitions reflects the presence
      of a significant O 2p component in the conduction band.

PMID- 16986074
TI  - Electronic spectra of uranyl chloride complexes in acetone: a CASSCF/CASPT2
      investigation.
AB  - A theoretical study is presented of the electronic spectra of the complexes
      UO(2)Cl(2)ac(4), UO(2)Cl(2)ac(3), [UO(2)Cl(3)ac(2)](-) and [UO(2)Cl(3)ac](-) (ac
      = acetone) using perturbation theory based on a complete-active-space type
      wavefunction (CASSCF/CASPT2). Both scalar relativistic effects and spin-orbit
      coupling were included in the calculations. The calculated excitation energies
      and oscillator strength values have been compared to the experimental absorption
      spectrum for uranyl chloride complexes in acetone solution, for chloride-to
      uranyl ratios between two and three. The main purpose of this work was to
      investigate the origin of the remarkable intensity increase observed in the lower
      part of the experimental absorption spectra, upon addition of chloride to uranyl
      complexes in acetone. The calculated excitation energies for the different
      complexes are similar and closely correspond to the experimental data. However,
      in none of the theoretical spectra, the high intensities observed in the lower
      part of the experimental spectrum are reproduced.

PMID- 16986075
TI  - Probing spin-orbit mixing and the singlet-triplet gap in dichloromethylene via Ka
      sorted emission spectra.
AB  - The magnitude of the singlet-triplet gap in dichloromethylene (CCl(2)) has been a
      point of controversy in the recent literature. In this study, we report single
      vibronic level emission spectra of the A(1)B(1)-->X[combining tilde](1)A(1)
      system of the carbene C(35)Cl(2), which probes the vibrational structure of the
      X[combining tilde](1)A(1) state up to approximately 10,000 cm(-1) above the
      vibrationless level. By the careful selection of bands where complete isotope and
      K(a)' selectivity in excitation was possible, we measured K(a)'-sorted emission
      spectra in order to test the previously established hypothesis [M.-L. Liu, C.-L.
      Lee, A. Bezant, G. Tarczay, R. J. Clark, T. A. Miller and B.-C. Chang, Phys.
      Chem. Chem. Phys., 2003, 5, 1352] that unassigned lines lying above approximately
      5,000 cm(-1) belong to levels of the a(3)B(1) state. The K(a)'-sorting method
      discriminates between singlet and triplet levels via the (A''-B[combining
      macron]'') rotational constant, which is significantly larger for pure triplet
      levels due to the larger equilibrium bond angle. In the region between 3,500 and
      9,000 cm(-1) above the vibrationless level of the X[combining tilde](1)A(1)
      state, we find only a very modest increase in (A''-B[combining macron]''), and
      approximately 86% of the lines observed between 5,000 and 9,000 cm(-1) can be
      assigned to X[combining tilde](1)A(1) levels within 3 standard deviations of our
      Dunham expansion fit, which included more than 140 levels in total. A nearly
      complete set of Dunham parameters was determined for the C(35)Cl(2) isotopomer,
      and the X[combining tilde](1)A(1) state term energies up to 4,000 cm(-1) are in
      excellent agreement with recent variational calculations of Tarczay, et al. [G.
      Tarczay, T. A. Miller, G, Czako and A. G. Csaszar, Phys. Chem. Chem. Phys., 2005,
      7, 2881]. Finally, the implication of our results for the singlet-triplet gap in
      dichloromethylene is discussed.

PMID- 16986076
TI  - Extended tunnelling states in the benzoic acid crystal: infrared and Raman
      spectra of the OH and OD stretching modes.
AB  - We compare Raman and infrared spectra of the nuOH/OD modes in benzoic acid
      crystal powders at 7 K. The extremely sharp Raman bands contrast to the broad
      infrared profiles and suggest adiabatic separation of hydrogen (deuterium)
      dynamics from the crystal lattice. There is no evidence of any proton-proton
      coupling term. The assignment scheme is consistent with a quasisymmetric double
      minimum potential, largely temperature independent. Tunnel splitting is a major
      band shaping mechanism, in addition to anharmonic coupling with lattice modes.
      The proton/deuteron dynamics are rationalized with nonlocal pseudoparticles and
      extended states. We propose a symmetry-related damping mechanism to account for
      the broad infrared profiles, as opposed to the sharp Raman bands. We assign
      spectral features to distinct interconversion mechanisms based on either
      pseudoparticle transfer or adiabatic pairwise transfer. We establish close
      contacts with theoretical models based on first-principles calculations.

PMID- 16986077
TI  - The reaction products of the 193 nm photolysis of vinyl bromide and vinyl
      chloride studied by time-resolved Fourier transform infrared emission
      spectroscopy.
AB  - Time-resolved Fourier transform infrared (TRFTIR) emission spectroscopy has been
      used to study the 193 nm photolysis of vinyl bromide (C(2)H(3)Br) and vinyl
      chloride (C(2)H(3)Cl). Time-resolved IR emission was analysed to obtain nascent
      vibrational state populations of two primary photolysis products: HBr (v = 1-7)
      and HCl (v = 1-6). In both cases the nascent vibrational state populations
      monotonically decrease with increasing v and are in excellent agreement with
      previously published data. Time-resolved populations were analysed to yield rate
      constants for vibrational relaxation of HBr (v = 1-3) and HCl (v = 1-4) by parent
      vinyl bromide and vinyl chloride, respectively. In both cases the rate constants
      were found to increase with increasing vibrational quantum number, in agreement
      with a single quantum de-excitation via vibrational to vibrational energy
      transfer. Butadiene (C(4)H(6)) was identified as a secondary product of the
      photolysis of both vinyl halides, and shown to be formed from the reaction of
      parent vinyl halide with the vinyl radical. The presence of a buffer gas was
      found to produce a strong emission feature centred at 2,200 cm(-1), the intensity
      of which was dependent on the pressure of the buffer gas used, and whose kinetics
      are indicative of a secondary reaction product. We propose that this emission is
      from the vibrational progression of the electronic transition A(0, v, 1) --> X(0,
      v, 2) in the secondary reaction product C(2)H, whose formation route is favoured
      by the presence of buffer gas.

PMID- 16986078
TI  - On the physical nature of mesophases of guanosine gels.
AB  - The unusual columnar aqueous mesophases of self-assembled guanosine stacks, such
      as 2'-deoxyguanosine 5'-monophosphate and 2'-deoxyguanosine 3'-monophosphate, are
      analyzed in terms of a general theory of azimuthal correlations between the
      charged helices. This theory considers forces, specific to the helical structure
      of each macromolecule, which depend on the azimuthal orientations of the
      molecules about their long axes. More specifically, in determining the magnitudes
      and decay lengths of these helix specific forces we utilize the Kornyshev-Leikin
      theory of electrostatic interaction between helical macromolecules and
      quantitatively fit experimental data. Together with explaining a number of the
      observed features of these mesophases, several new effects are predicted.
      Possible limitations and developments of our theoretical model are discussed, as
      well as new experiments to test the implications of the theory.

PMID- 16986079
TI  - Chemisorption of HCl to the MgO(001) surface: a DFT study.
AB  - We use plane wave and embedded cluster ab initio density functional calculations
      to study adsorption, dissociation and diffusion of the HCl molecule on the
      MgO(001) surface. The two methods yield comparable results for adsorption of an
      isolated HCl molecule and complement each other when considering charged species
      and coverage effects. We find dissociative chemisorption at a coverage smaller
      than 0.5 monolayer with a Cl(-) ion electrostatically coupled to the OH(-) ion at
      the surface oxygen site. The adsorption energy of the Cl(-)[dot dot dot](OH)(-)
      complex is 1.5 eV and the activation energy of Cl(-) diffusion away from OH(-) is
      0.6 eV. There is no significant activation energy for rotation of Cl(-) around
      the adsorption site. At rising coverage, an increase in dipole-dipole repulsion
      between HCl molecules leads to a lowering of the adsorption energy per HCl and a
      change of binding towards hydrogen-bridge type as well as a lowering of the
      activation energy for Cl(-) diffusion. OH(-) formed in the surface due to HCl
      adsorption has a stretch frequency of 3,083 cm(-1) with Cl(-) associated and
      3,648 cm(-1) with Cl(-) removed.

PMID- 16986080
TI  - [Drug therapy in the treatment of glaucoma].

PMID- 16986081
TI  - [Posterior segment complications of laser in situ keratomileusis (LASIK)--a
      survey of the literature].
AB  - During the past years refractive surgical procedures and particularly laser IN
      SITU keratomileusis (LASIK) have become established by clinical and experimental
      studies and are performed worldwide in a high number. This paper provides a
      survey of the published posterior segment complications of LASIK that may occur
      albeit very rarely. Additionally, current clinical and experimental hypotheses
      regarding the pathogenesis of those complications are discussed. Currently a
      cause-effect relationship between LASIK and reported posterior segment
      complications has not been proven although a very high number of LASIK procedures
      have been performed worldwide.

PMID- 16986082
TI  - [Alternative medicine in ophthalmology?].
AB  - In an overview new data from the literature regarding alternative/complementary
      medicine are presented. Naturopathy, acupuncture and homeopathy as well as new
      findings in placebo-research and their correlation to alternative medicine are
      discussed. In addition, as a synthesis a patient-orientated so-called
      anthropologic medicine is recommended to make alternative/complementary medicine
      unnecessary.

PMID- 16986083
TI  - [Confocal microscopy in corneal dystrophies: a comparison between confocal slit
      scanning (ConfoScan P2) and laser scanning microscopy (Rostock Cornea Modul-HRT
      II)].
AB  - BACKGROUND: The object of this work was a comparison of confocal images of
      corneal dystrophies made by a slit scanning microscope versus a laser scanning
      microscope. MATERIAL AND METHODS: Using the Rostock Cornea Modul-HRT II as a
      confocal laser scanning microscope the images of five patients with some
      epithelial, stromal and endothelial corneal dystrophies were acquired. The
      pictures were compared qualitatively with those taken by the slit scanning
      microscope "ConfoScan P2" from corresponding pathologies. Also, the images of
      normal corneas of ten healthy persons were acquired for a qualitative comparison.
      RESULTS: Confocal images from both devices were able to provide significant
      helpful diagnostic findings about the corneal microstructure. Essential
      qualitative differences between the images of both devices used were not
      observed. Due to the additional hardware components and the software module for
      image acquisition, analysis and archiving, the RCM-HRT II is favoured over the
      "ConfoScan P2". Nevertheless, the evaluation in favour of the RCM-HRT II has to
      be confined because an optimised, user-friendly enhancement, the "ConfoScan 4" is
      currently available. CONCLUSION: Evaluating corneal dystrophies in vivo, an
      equivalent utility of both technical approaches has been observed.

PMID- 16986084
TI  - [Long-term follow-up of selective laser trabeculoplasty in primary open-angle
      glaucoma].
AB  - BACKGROUND: Our aim was to investigate the outcomes of selective laser
      trabeculoplasty (SLT) for the treatment of primary open-angle glaucoma (POAG) in
      a prospective clinical study. PATIENTS AND METHODS: In 90 eyes suffering from
      POAG, treatment was carried out with a frequency-doubled, Q-switched Nd:YAG laser
      (532 nm). The intraocular pressure (IOP) was measured before the treatment and 1,
      3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66 and 72 months after. A failure was
      defined as an IOP reduction of less than 20 % of the pretreatment IOP, or a
      progression of visual field or optic disc damage requiring filtering surgery. The
      hypotensive medication during the study period remained unchanged. RESULTS: The
      mean follow-up time was 41.2 months (SD 20.0). The mean pretreatment IOP was 22.4
      mmHg (SD 2.3). At one month of follow-up, the mean IOP reduction was 5.0 mmHg (SD
      2.3) or 22.3 % and at 6 months 5.2 mmHg (SD 2.4) or 23.2 %. At 12 months of
      follow-up, the mean IOP reduction was 5.4 mmHg (SD 2.4) or 24.0 % and at 24
      months 5.8 mmHg (SD 2.3) or 25.5 %. At 36 months of follow-up, the mean IOP
      reduction was 5.7 mmHg (SD 2.1) or 25.1 % and at 48 months of follow-up, the mean
      IOP reduction was 5.2 mmHg (SD 1.9) or 23.1 %. At 60 months of follow-up, the
      mean IOP reduction was 5.2 mmHg (SD 2.0) or 22.6 % and at the end of 72 months of
      follow-up, the mean IOP reduction was 5.4 mmHg (SD 2.3) or 22.8 %. The success
      rate after 12 months determined by Kaplan-Meier survival analysis was 94 %, after
      24 months 85 %, after 36 months 74 %, after 48 months 68 % and after 72 months 59
      %. CONCLUSION: SLT is an effective procedure offering an additional therapy
      option for the treatment of POAG, but the effect diminishes over time.

PMID- 16986085
TI  - [Advanced glycation end products and pseudoexfoliation--correlation between
      clinical outcome and histological findings].
AB  - BACKGROUND: Pseudoexfoliation syndrome (PXS) as a stress-induced
      microfibrillopathy often shows a prolonged postoperative course. Formation of
      advanced glycation end products (AGEs) might be also associated with an increased
      oxidative stress. This study investigated for the first time
      immunohistochemically lens capsules of PXS patients for the AGE
      carboxymethylysine (CML) and correlated the findings with the clinical outcome of
      the patients. METHODS: 55 patients (22 male, 33 female; mean age 73.9 +/- 14.1
      years) with PXS and pseudoexfoliation glaucoma (PXG) after cataract extraction
      were included. All lens capsules could be investigated immunohistochemically for
      the AGE CML. Both preoperative biometric data as well as intra- and postoperative
      courses were included in the investigations, followed by a correlation analysis
      of the immunohistochemical findings. RESULTS: 29 PXS and 26 PXG patients with a
      mean axial length of 23.1 +/- 1.1 mm were explored. Both groups showed a
      postoperative decrease of intraocular pressure and a moderate increase of visual
      acuity. Intraoperatively, 6 zonulolyses occurred and postoperatively 11 patients
      showed problems like increases of intraocular pressure. Immunohistochemically,
      CML could be detected in most of the epithelial cells of the lens capsules but
      only in a small part of the pseudoexfoliation (PEX) fibrils. A correlation
      between positive CML immunoreaction and the clinical course was not detectable.
      CONCLUSIONS: Cataract extraction in patients with PEX glaucoma shows different
      specialities and risks. The AGE CML was detectable in human lens capsules. A
      direct correlation between clinical course and immunohistochemical reaction of
      the PEX fibrils could not be found. Overall, CML seems not to be a valuable
      predictive factor for the clinical course in patients with PXS and PXG.

PMID- 16986086
TI  - [Comparison of Preferential Hyperacuity Perimeter (PHP) test and Amsler grid test
      in the diagnosis of different stages of age-related macular degeneration].
AB  - BACKGROUND: Age-related macular degeneration (ARMD) is the leading cause of
      blindness in people over 65 years of age. A rapid loss of vision occurs
      especially in cases with choroidal neovascularisation. Early detection of ARMD
      and timely treatment are mandatory. We have prospectively studied the results of
      two diagnostic self tests for the early detection of metamorphopsia and scotoma,
      the PHP test and the Amsler grid test, in different stages of ARMD. PATIENTS AND
      METHODS: Patients with ARMD and best corrected visual acuity of 6/30 or better
      (Snellen charts) were examined with a standardised protocol, including supervised
      Amsler grid examination and PHP, a new device for metamorphopsia or scotoma
      measurement, based on the hyperacuity phenomenon in the central 14 degrees of the
      visual field. The stages of ARMD were independently graded in a masked fashion by
      stereoscopic ophthalmoscopy, stereoscopic fundus colour photographs, fluorescein
      angiography, and OCT. The patients were subdivided into 3 non-neovascular groups
      [early, late (RPE atrophy > 175 microm) and geographic atrophy], a neovascular
      group (classic and occult CNV) and an age-matched control group (healthy
      volunteers). RESULTS: 140 patients, with ages ranging from 50 to 90 years (median
      68 years), were included in the study. Best corrected visual acuity ranged from
      6/30 to 6/6 with a median of 6/12. 95 patients were diagnosed as non-neovascular
      ARMD. Thirty eyes had early ARMD (9 were tested positive by the PHP test and 9 by
      the Amsler grid test), and 50 late ARMD (positive: PHP test 23, Amsler grid test
      26). The group with geographic atrophy consisted of 15 eyes (positive: PHP test
      13, Amsler grid test 10). Forty-five patients presented with neovascular ARMD
      (positive: PHP test 38, Amsler grid test 36), 34 volunteers served as control
      group (positive: PHP test 1, Amsler grid test 5). CONCLUSIONS: The PHP and Amsler
      grid tests revealed comparable results detecting metamorphopsia and scotoma in
      early ARMD (30 vs. 30 %) and late ARMD (46 vs. 52 %). However, the PHP test more
      often revealed disease-related functional changes in the groups of geographic
      atrophy (87 vs. 67 %) and neovascular ARMD (84 vs. 80 %). This implies that the
      PHP and Amsler grid self tests are useful tools for detection of ARMD and that
      the PHP test has a greater sensitivity in the groups of geographic atrophy and
      neovascular AMD.

PMID- 16986087
TI  - [Digital patient record for remote monitoring of intraocular pressure, blood
      pressure and serum glucose].
AB  - BACKGROUND: At the University Eye Hospital of Greifswald, we have developed a
      digital patient record that allows close monitoring of glaucoma, diabetes and
      hypertension. The record stores contemporary, long-term profiles containing
      intraday variation and interaction of intraocular pressure, blood pressure and
      serum glucose levels even at night. METHODS: All patients are equipped with a
      home monitoring system. They subsequently transmit self-measurements via the
      "telemedical interface" to the server. Physicians use a web front-end to access
      electronic patient records; this provides a PDF export filter for printing. We
      intend to include a total number of 120 patients from Mecklenburg-Vorpommern who
      suffer from glaucoma possibly combined with hypertension/diabetes. This long-term
      investigation was designed as a randomised cross-over study in two groups.
      RESULTS: Especially for this project an electronic patient record was developed
      and implemented. The components of the home monitoring system were modified and
      connected to a custom-built "telemedical interface". To date the study includes
      120 patients, 60 of whom constantly measure and transmit their values to the
      electronic patient record, while the others are treated without home monitoring.
      All self-measurements are presented in a tabular form. In addition, dynamically
      generated graphics provide a diagrammatic view of all values. On demand, a
      detailed protocol for every single measurement report allows a comprehensive
      evaluation of the quality of the self-measurements. Ocular perfusion pressure is
      calculated automatically from intraocular pressure and blood pressure. The
      presented system documents continuously all information that is relevant for
      treatment and provides fast access for all attending physicians. CONCLUSIONS:
      Central data collection and unlocalised access improve information exchange
      between involved physicians. Flexible measurement periods allow the detection of
      pressure spikes even at night. In addition, this may help to classify glaucoma
      (normal-pressure glaucoma) and its causal connection to blood pressure. The
      patients benefit from individualised therapy adaptation and early therapeutic
      intervention in case of critical parameters.

PMID- 16986088
TI  - [Eyelid swelling caused by a meningioma in an 8-year-old girl. Case report and
      review of the diagnosis and the treatment for meningiomas in childhood and
      adolescence].
AB  - BACKGROUND: Tumours of the eyelid and orbit with different biological behaviour
      and localisation may cause eyelid swelling. Orbital meningiomas are rare,
      particularly in childhood and adolescence. CASE REPORT: We report the case of an
      8-year-old girl with frontobasal meningioma, who was admitted to the hospital
      because of a one-sided upper eyelid swelling. With the example of this case, the
      diagnosis, treatment and aftercare of meningiomas in childhood and adolescence
      will be discussed. CONCLUSIONS: The treatment strategy of meningiomas in
      childhood requires a close interdisciplinary cooperation of ophthalmology,
      paediatric oncology, neurosurgery and radiotherapy. Moreover, controlled
      investigations should yield information about the efficiency of modern
      irradiation techniques or adjuvant chemotherapy in the treatment of inoperable or
      malignant meningiomas.

PMID- 16986089
TI  - [Sebaceous carcinoma of the eyelids--case reports and review of the literature].
AB  - BACKGROUND: Sebaceous carcinomas are among the most rarely found skin tumours
      (0.2 - 4.6 %). As with most skin tumours the predominant region of occurrence is
      the head and neck, in particular the eyelids. The cytological origins are
      foremost the Meibomian and the glands of Zeis. CASE REPORTS: We report on two
      female patients suffering from sebaceous carcinoma of the upper and lower lid.
      The time span from initial treatment up to definite diagnosis and treatment was
      one year. In both cases the tumour was radically removed surgically and the
      eyelid reconstructed. In the first case there was no tumour recurrence within six
      years after surgery. In the second case a lymph node metastasis of the parotid
      gland was found seven years after initial therapy and surgically removed followed
      by a complete parotidectomy and neck dissection. DISCUSSION: As the sebaceous
      carcinomas are difficult to differentiate from other kinds of benign and
      malignant eyelid diseases, a considerable delay between the initial examination
      and final diagnosis is not uncommon. This type of tumour is characterised by a
      high degree of biological aggression concerning local recurrence and lymphogenous
      and hematogenic tumour spread. The mortality rate is reported to be between 9 and
      40 %. Therapy of choice is the radical surgical removal of the tumour. Depending
      on preoperative findings, neck dissection may be indicated. The biological
      behaviour of this kind of tumour requires long-term oncological aftercare.

PMID- 16986090
TI  - [Bitemporal hemianopia in road traffic].
AB  - BACKGROUND: Patients suffering from pituitary adenomas and diseases of the
      chiasma typically show a bitemporal hemianopia. The residual undisturbed nasal
      visual fields of both eyes should have an extension of (at least) 120 degrees and
      are according to the actual German traffic rules (FeVAndV) for cars of the
      classes A, B, M, L and T. The intact half fields fit geometrically to one virtual
      normal field, that seems to correspond in the centre of a normal field. Reports
      on this problem often do not address correctly the questions of suitability for
      participation in road traffic. PATIENTS: The case of a patient with typical
      bitemporal hemianopia illustrates the sensorial peculiarities: the functioning
      temporal retinal halves do not correspond. This patient suffered additionally
      from disturbing diplopia due to a small-angle exotropia. The extent of the
      performed eye muscle surgery was selected to induce a slight overcorrection, i.
      e., resulting in 3 to 5 degrees esotropia. This eliminated the diplopia, but
      resulted in a vertical scotoma of the extension of the esotropia. CONCLUSIONS: In
      bitemporal hemianopia the undisturbed nasal visual half fields do not add up to a
      "nearly normal field of one eye". Moreover, either diplopia or--much more
      dangerous in traffic--a central vertical scotoma is the result. The explanation
      for this is a sliding of the hemifields of each eye without stabilisation by
      corresponding areas of the retinas of the right and left eyes. The peripheral
      extension of the visual field is not the key to the problem to imagine how a
      patient with typical bitemporal hemianopia will visualise daily life and traffic.
      In bitemporal hemianopia there is substantially no eligibility for driving a car
      or motor bicycle in road traffic.

PMID- 16986091
TI  - Company profile: high-tech instruments for Particle Size Analysis (PSA) from
      Sympatec, a global pioneer for lab and line in the unique size range from 1
      nanometre to 20 millimetres.

PMID- 16986096
TI  - Editorial: advances in jet-based approaches.

PMID- 16986099
TI  - Euroscience Open Forum 2006.

PMID- 16986101
TI  - South Korea continues up ladder of biotech leaders.

PMID- 16986103
TI  - Research project: Charleston Bioengineered Kidney Project.
AB  - The goal of Charleston Bioengineered Kidney Project is to engineer a functional
      living human kidney suitable for surgical implantation using principles of
      directed tissue self-assembly and tissue fusion. This is a multidisciplinary
      project which incorporates multiple innovative bioengineering technologies and
      expertise from a broad spectrum of disciplines. The conceptual framework,
      engineering principles, design, potential cell source as well as the first
      preliminary data demonstrating the feasibility of the proposed Charleston
      Bioengineered Kidney Project are outlined. The potential challenges are
      described. Finally, the experts' opinion about the proposed project is also
      presented.

PMID- 16986104
TI  - Magnetic resonance imaging of gadolinium-labeled pancreatic islets for
      experimental transplantation.
AB  - New imaging techniques that couple anatomical resolution to sensitivity may
      greatly contribute to improving islet transplantation. In the present work, a
      report is given of the direct detection of islets by magnetic resonance imaging
      (MRI) after ex vivo cell labeling with the MRI T(1) contrast agent GdHPDO3A.
      Experiments on mouse and human islets demonstrated well-tolerated uptake of
      GdHPDO3A, based on morphology, viability, glucose-dependent insulin response and
      apoptosis/toxicity gene array profile. GdHPDO3A loading was sufficient for in
      vitro MRI cell detection. In vivo isotransplanted mouse islets into the kidney
      capsule and xenotransplanted human islets within the mouse liver were detected.
      Imaging specificity was supported by the absence of signal in unlabeled islet
      transplants, its persistence upon using fat-suppression MRI protocols and the
      colocalization with the transplanted islets. In conclusion, direct islet imaging
      with high spatial and contrast resolution after labeling with GdHPDO3A is
      demonstrated, allowing visualization of kidney subcapsular mouse islet grafts and
      intrahepatic human islet xenografts.

PMID- 16986105
TI  - Latin American Cancer Research Coalition. Community primary care/academic
      partnership model for cancer control.
AB  - The Latin American Cancer Research Coalition (LACRC) was funded by NCI as a
      Special Populations Network to 1) provide training to clinic staff in cancer
      control and foster development of Latino faculty training, 2) conduct a needs
      assessment with the community clinics, 3) enhance the ability of the clinics to
      promote healthy lifestyles, 4) collaborate on research projects to improve use of
      early detection, and 5) explore partnerships to increase access to culturally
      competent cancer care. The LACRC developed a model for cancer control focused on
      community-based clinics as the focal point for in-reach and community outreach
      targeted to Latinos to reduce cancer disparities. This framework was designed to
      link the community to local hospitals and academic centers, build capacity, and
      promote diffusion of innovations directly into delivery systems. Eight research
      projects submitted by junior investigator/clinic teams have been funded by NCI.
      These research projects range from recruiting for clinical trials to prevention
      to survivorship. The LACRC has trained 6 cancer control coordinators from partner
      sites and educated 59 undergraduate minority student interns in aspects of cancer
      control research. Central to LACRC's success to date has been the creation and
      maintenance of an infrastructure of trusting relationships, especially those
      developed between clinician/investigators and individuals within the greater
      Latino community. Community clinics can be effective agents for cancer control
      among Latinos. Latinos are likely to participate in research conducted by
      culturally representative teams of researchers using culturally appropriate
      recruiting strategies. Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16986106
TI  - Apparent diffusion coefficient histograms may predict low-grade glioma subtype.
AB  - The subtypes of glioma are known to have different prognosis and response to
      treatment. The purpose of this work was to investigate whether apparent diffusion
      coefficient (ADC) histograms of untreated low-grade astrocytomas and
      oligodendrogliomas exhibit different characteristics due to their biological
      differences, and whether a diagnosis of tumour subtype can be made at
      presentation using the histogram alone, which, if possible, would have an impact
      on clinical practise. Fifteen patients with astrocytoma (AC) [11 male (mean age
      +/- standard deviation) 40 +/- 11 years], nine with oligodendroglioma (OD) (four
      male, 45 +/- 13 years) and three with oligoastrocytoma (OA) (two male, 60 +/- 11
      years) were recruited and diffusion-weighted images (b = 0 and 1000 s mm(-2))
      were acquired every 6 months to date or until malignant transformation. Whole
      tumour ADC histograms were calculated, a multiple discriminant analysis was
      performed and quantitative morphological parameters extracted, the AC and OD
      subtypes were then compared using Student's unpaired t-test. Classification of
      the histograms was also performed. ODs had significantly lower group ADC values
      than ACs and up to 83% of the subjects could be correctly classified into the OD
      and AC groups by reference to the histogram. The group differences were most
      significant for the multiple discriminant analysis (p = 1 x 10(-5)) and at the
      10th centile point [AC = 1170 +/- 170, OD = (1030 +/- 80) x 10(-6) mm(2) s(-1)]
      (p = 0.01). ODs have a lower ADC than ACs with differences throughout the
      histogram. Both tumour types show similar intra-tumour heterogeneity, as seen
      from the equal group peak heights, but ACs shows more intra-group heterogeneity.
      ADC histogram analysis may aid non-invasive sub-classification of low-grade
      glioma histological subtypes.

PMID- 16986107
TI  - Precision in measurements of perfusion and microvascular permeability with T1
      weighted dynamic contrast-enhanced MRI.
AB  - Dynamic contrast-enhanced MRI is used to estimate microvascular parameters by
      tracer kinetics analysis. The time for the contrast agent to travel from the
      artery to the tissue of interest (bolus arrival time (BAT)) is an important
      parameter that must be measured in such studies because inaccurate estimates or
      neglect of BAT contribute to inaccuracy in model fitting. Furthermore, although
      the precision with which these parameters are estimated is very important, it is
      rarely reported. To address these issues, two investigations were undertaken.
      First, simulated data were used to validate an independent method for estimation
      of BAT. Second, the adiabatic approximation to the tissue homogeneity model was
      fitted to experimental data acquired in prostate and muscle tissue of 22 patients
      with prostate cancer. A bootstrap error analysis was performed to estimate the
      precision of parameter estimates. The independent method of estimating BAT was
      found to be more accurate and precise than a model-fitting approach. Estimated
      precisions for parameters measured in the prostate gland were 14% for extraction
      fraction (median coefficient of variation), 19% for blood flow, 28% for
      permeability-surface area product, 35% for volume of the extravascular
      extracellular space, and 36% for blood volume. Techniques to further reduce
      uncertainty are discussed.

PMID- 16986108
TI  - Denoising of complex MRI data by wavelet-domain filtering: application to high-b
      value diffusion-weighted imaging.
AB  - The Rician distribution of noise in magnitude magnetic resonance (MR) images is
      particularly problematic in low signal-to-noise ratio (SNR) regions. The Rician
      noise distribution causes a nonzero minimum signal in the image, which is often
      referred to as the rectified noise floor. True low signal is likely to be
      concealed in the noise, and quantification is severely hampered in low-SNR
      regions. To address this problem we performed noise reduction (or denoising) by
      Wiener-like filtering in the wavelet domain. The filtering was applied to complex
      MRI data before construction of the magnitude image. The noise-reduction
      algorithm was applied to simulated and experimental diffusion-weighted (DW)
      images. Denoising considerably reduced the signal standard deviation (SD, by up
      to 87% in simulated images) and decreased the background noise floor (by
      approximately a factor of 6 in simulated and experimental images).

PMID- 16986109
TI  - Determination of the maturity and functionality of tumor vasculature by MRI:
      correlation between BOLD-MRI and DCE-MRI using P792 in experimental fibrosarcoma
      tumors.
AB  - Using hypercapnia and carbogen as functional markers of vessel maturation and
      function, we compared blood oxygen level-dependent (BOLD) contrast with standard
      dynamic contrast-enhanced (DCE)-MRI quantitative parameters in murine
      fibrosarcoma. Our results show that there was no correlation between vessel
      maturity and contrast-agent uptake rate (K(in) (Trans)) or contrast agent efflux
      rate (k(ep)). In addition, DCE-MRI provided higher estimates of the fraction of
      functional tumor compared to BOLD-MRI. The two putative markers of regional
      vascular density, i.e., the magnitude of BOLD signal change during carbogen
      challenge (VF) and the fractional plasma volume found by DCE-MRI (V(p)), were
      only weakly correlated (r(2) = 0.02-0.14). Furthermore, VF showed no correlation
      with K(in) (Trans). A positive correlation was observed (r(2) = 0.75) between
      mean tumor VF and k(ep), but only when averaged over the whole tumor (which
      includes tumor regions completely unperfused by the gadolinium (Gd) contrast
      agent). This would merely reveal a relationship between perfusion status and the
      capacity to respond to carbogen breathing. In conclusion, characterizations of
      tumor microvasculature imaging using BOLD-MRI and DCE-MRI appear to be largely
      complementary, given the weak correlations between their corresponding derived
      parameters.

PMID- 16986110
TI  - Fully balanced steady-state 3D-spin-echo (bSSSE) imaging at 3 Tesla.
AB  - In this work a 3D fully balanced steady-state spin-echo sequence (bSSSE) was
      designed and implemented on a 3-Tesla whole-body MR scanner. In contrast to
      previously introduced nonbalanced SSSE (nbSSSE) sequences, bSSSE features fully
      rewound imaging gradients. Additionally, all phase encodings and the readout
      prephasing are performed after the refocusing pulse. Its performance was compared
      with previously used gradient-echo (GE) and nbSSSE sequences. The signal response
      of each sequence was simulated by numerical solution of the Bloch equation. All
      sequences were then optimized based on these simulations for high-resolution (HR)
      imaging of tissues with short relaxation times and applied to in vivo HR-MRI of
      trabecular bone. bSSSE outperformed nbSSSE sequences in terms of SNR and SNR
      efficiency. Measurements of structural bone parameters revealed thinner
      trabeculae and a lower bone/bone-marrow fraction for the bSSSE sequence compared
      to the nbSSSE sequence. By applying a parallel imaging technique based on
      generalized autocalibrating partially parallel acquisition (GRAPPA) with a
      reduction factor of 2, we were able to maintain a clinically feasible scan time
      using bSSSE. Comparisons of structural bone parameters revealed a difference of
      less than 3% for all structural parameters between parallel and conventional
      imaging.

PMID- 16986111
TI  - Nonlinear phase correction of navigated multi-coil diffusion images.
AB  - Cardiac pulsatility causes a nonrigid motion of the brain. In multi-shot
      diffusion imaging this leads to spatially varying phase changes that must be
      corrected. A conjugate gradient based reconstruction is presented that includes
      phase changes measured using two-dimensional navigator echoes, coil sensitivity
      information, navigator-determined weightings, and data from multiple coils and
      averages.A multi-shot echo planar sequence was used to image brain regions where
      pulsatile motion is not uniform. Reduced susceptibility artifacts were observed
      compared to a clinical single-shot sequence. In a higher slice, fiber directions
      derived from single-shot data show distortions from anatomical scans by as much
      as 7 mm compared to less than 2 mm for our multi-shot reconstructions. The
      reduced distortions imply that phase encoding can be applied in the shorter left
      right direction, enabling time savings through the use of a rectangular field of
      view. Higher resolution diffusion imaging in the spine permits visualization of a
      nerve root.

PMID- 16986112
TI  - Dual vessel arterial spin labeling scheme for regional perfusion imaging.
AB  - Regional perfusion imaging (RPI) based on pulsed arterial spin labeling and
      angulated inversion slabs has been recently proposed. The technique allows
      mapping of individual brain perfusion territories of the major feeding arteries
      and could become a valuable clinical tool for evaluation of patients with
      cerebrovascular diseases. Here we propose a new labeling scheme for RPI where
      lateral and posterior circulations are labeled simultaneously. Two scans instead
      of three are sufficient to obtain the same perfusion territories as in the
      original approach, allowing for a 33% reduction in the total RPI protocol time.
      Moreover, the position of the inversion slabs with respect to vascular anatomy
      facilitates the planning and allows potentially better labeling efficiency. The
      new approach was tested on seven healthy volunteers and compared to the original
      labeling scheme. The results showed that the same perfusion territories and
      regional CBF values can be obtained.

PMID- 16986113
TI  - 1[alpha],25-dihydroxyvitamin D(3) enhances annexin II dependent proliferation of
      osteoblasts.
AB  - Cells experience a variety of physiological and non-physiological stresses and
      consequently have appropriate mechanisms to deal with such deviations from
      homeostasis. Particularly subject to mechanical stress and shear forces are the
      cells that make up the bones. Osteoblastic cells can interpret this stress as a
      stimulus for proliferation; however, the molecular mechanisms underlying this
      phenomenon are poorly understood. We have identified annexin II as being
      specifically upregulated in mechanically stressed osteoblasts and found that
      increased levels of this protein are necessary for 1[alpha],25-dihydroxyvitamin
      D(3) mediated augmentation of the proliferative response of osteoblasts after
      mechanical stress. Our data demonstrate a novel interaction between 1[alpha],25
      dihydroxyvitamin D(3) and annexin II in the proliferative response of osteoblasts
      as well as a novel function for annexin II in the stress response. These findings
      may offer new therapeutic opportunities for conditions that require regenerative
      osteoblastic activity such as osteoporosis.

PMID- 16986116
TI  - MRI for development of disease-modifying osteoarthritis drugs.
AB  - MRI has advantages as an imaging modality for drug development through its
      potential to provide information regarding localized morphological parameters, in
      addition to metrics of the structural and molecular state of cartilage. These
      metrics have the potential to provide earlier indications of pathology and may
      progress more rapidly than radiographic measures. These combined scans of
      localized morphology and matrix parameters will most likely provide a fuller
      assessment of cartilage state and will improve the cost and practicality of an
      overall evaluation of cartilage status by MRI. In the first part of this review,
      the relevant parameters are presented in terms of the information content they
      might provide in the drug development process. In the second part, applications
      of the MRI parameters in preclinical and clinical drug development are presented.

PMID- 16986117
TI  - MR in oncology drug development.
AB  - This article reviews the use of MR in preclinical and clinical experiments to aid
      drug development. In particular it concentrates on the use of MR to study tumor
      microvasculature following treatment with anti-vascular agents and the use of MRS
      to study tumor metabolism following treatment with a variety of anti-cancer
      agents. The advantages and disadvantages of a variety of techniques including
      contrast- and noncontrast-enhanced methods are discussed and the data from
      clinical trials using these techniques are reviewed. Despite the consensus
      documents produced to date for both dynamic contrast-enhanced MRI and MRS, most
      of the trials reported used alternative methods, and different nomenclature for
      the MR parameters used. This continues to inhibit the comparison between novel
      therapeutics and between different trials with the same compound. Comprehensive
      data from multicenter trials on the reproducibility of techniques is still
      lacking in the literature and the implications of the available data on clinical
      trial design is also discussed.

PMID- 16986115
TI  - Evaluation of treatment effects in Alzheimer's and other neurodegenerative
      diseases by MRI and MRS.
AB  - Neurodegeneration refers to a large clinically and pathologically heterogeneous
      disease entity associated with slowly progressive neuronal loss in different
      anatomical and functional systems of the brain. Neurodegenerative diseases often
      affect cognition, e.g. Alzheimer's disease (AD), dementia with Lewy bodies and
      vascular dementia, or different aspects of the motor system, e.g., amyotrophic
      lateral sclerosis, Parkinson's disease and ataxic disorders. Owing to increasing
      knowledge about the mechanisms leading to neurodegeneration, the development of
      treatments able to modify the neurodegenerative process becomes possible for the
      first time. Currently, clinical outcome measures are used to assess the efficacy
      of such treatments. However, most clinical outcome measures have a low test
      retest reliability and thus considerable measurement variance. Therefore, large
      patient populations and long observation times are needed to detect treatment
      effects. Furthermore, clinical outcome measures cannot distinguish between
      symptomatic and disease-modifying treatment effects. Therefore, alternative
      biomarkers including neuroimaging may take on a more important role in this
      process. Because MR scanners are widely available and allow for non-invasive
      detection and quantification of changes in brain structure and metabolism, there
      is increasing interest in the use of MRI/MRS to monitor objectively treatment
      effects in clinical trials of neurodegenerative diseases. Particularly volumetric
      MRI has been used to measure atrophy rates in treatment trials of AD because the
      relationship between atrophic changes and neuron loss is well established and
      correlates well with clinical measures. More research is needed to determine the
      value of other MR modalities, i.e. diffusion, perfusion and functional MRI and MR
      spectroscopy, for clinical trials with neuroprotective drugs.

PMID- 16986118
TI  - MR spectroscopy: its potential role for drug development for the treatment of
      psychiatric diseases.
AB  - Magnetic resonance spectroscopy (MRS) is likely in the near future to play a key
      role in the process of drug discovery and evaluation. As the pharmaceutical
      industry seeks biochemical markers of drug delivery, efficacy and toxicity, this
      non-invasive technique offers numerous ways to study adults and children
      repeatedly and without ionizing radiation. In this article, we survey an array of
      the information that MRS offers about neurochemistry in general and psychiatric
      disorders and their treatment in particular. We also present growing evidence of
      glial abnormalities in neuropsychiatric disorders and discuss what MRS is
      contributing to that line of investigation. The third major direction of this
      article is the discussion of where MRS techniques are headed and how those new
      techniques can contribute to studies of mechanisms of psychiatric disease and
      drug discovery.

PMID- 16986119
TI  - MRI of atherosclerosis in clinical trials.
AB  - Magnetic resonance imaging (MRI) of the arterial wall has emerged as a viable
      technology for characterizing atherosclerotic lesions in vivo, especially within
      carotid arteries and other large vessels. This capability has facilitated the use
      of carotid MRI in clinical trials to evaluate therapeutic effects on
      atherosclerotic lesions themselves. MRI is specifically able to characterize
      three important aspects of the lesion: size, composition and biological activity.
      Lesion size, expressed as a total wall volume, may be more sensitive than maximal
      vessel narrowing (stenosis) as a measure of therapeutic effects, as it reflects
      changes along the entire length of the lesion and accounts for vessel remodeling.
      Lesion composition (e.g. lipid, fibrous and calcified content) may reflect
      therapeutic effects that do not alter lesion size or stenosis, but cause a
      transition from a vulnerable plaque composition to a more stable one. Biological
      activity, most notably inflammation, is an emerging target for imaging that is
      thought to destabilize plaque and which may be a systemic marker of
      vulnerability. The ability of MRI to characterize each of these features in
      carotid atherosclerotic lesions gives it the potential, under certain
      circumstances, to replace traditional trials involving large numbers of subjects
      and hard end-points--heart attacks and strokes--with smaller, shorter trials
      involving imaging end-points. In this review, the state of the art in MRI of
      atherosclerosis is presented in terms of hardware, image acquisition protocols
      and post-processing. Also, the results of validation studies for measuring lesion
      size, composition and inflammation will be summarized. Finally, the status of
      several clinical trials involving MRI of atherosclerosis will be reviewed.

PMID- 16986120
TI  - Pharmacological FMRI in the development of new analgesic compounds.
AB  - Chronic pain is a major problem for the individual and for society. Despite a
      range of drugs being available to treat chronic pain, only inadequate pain relief
      can be achieved for many patients. There is therefore a need for the development
      of new analgesic compounds. The assessment of pain depends to date entirely on
      the subjective report of the patient, in contrast to many other clinical
      conditions where biomarkers that help determine the severity and stage of the
      disease enable the physician to monitor the course of the disease and treatment
      effects longitudinally. In this article, we illustrate that magnetic resonance
      based imaging techniques have the potential to provide sensitive and specific
      biomarkers of the pain experience, as well as clarifying disease mechanisms.
      Functional magnetic resonance imaging (FMRI) is particularly suited to
      investigating the effects of pharmacological agents on pain processing within the
      human central nervous system. Combination of FMRI and drug administration is
      termed pharmacological FMRI (phFMRI). In addition to outlining several
      methodological considerations that have to be taken into account when performing
      phFMRI, we discuss phFMRI studies that have already used this technique to study
      the effects of analgesic compounds. These studies provide promising data for the
      use of phFMRI as sensitive tool in assessing a potential drug effect. Such
      pharmacodynamic readouts obtained early in the process of drug development would
      not only save the pharmaceutical industry substantial amounts of money, but would
      also avoid the unnecessary exposure of patients to molecules with limited or no
      therapeutic value. We are therefore optimistic that phFMRI will be used as a tool
      with high sensitivity and specificity for evaluating analgesic agents in early
      drug development and clinical studies.

PMID- 16986121
TI  - Bioinformatic analysis of protein structure-function relationships: case study of
      leukocyte elastase (ELA2) missense mutations.
AB  - Cyclic and congenital neutropenia are caused by mutations in the human neutrophil
      elastase (HNE) gene (ELA2), leading to an immunodeficiency characterized by
      decreased or oscillating levels of neutrophils in the blood. The HNE mutations
      presumably cause loss of enzyme activity, consequently leading to compromised
      immune system function. To understand the structural basis for the disease, we
      implemented methods from bioinformatics to analyze all the known HNE missense
      mutations at both the sequence and structural level. Our results demonstrate that
      the 32 different mutations have diverse effects on HNE structure and function,
      affecting structural disorder and aggregation tendencies, stability maintaining
      contacts, and electrostatic properties. A large proportion of the mutations are
      located at conserved amino acids, which are usually essential in determining
      protein structure and function. The majority of the disease-causing HNE missense
      mutations lead to major structural changes and loss of stability in the protein.
      A few mutations also affect functional residues, leading into decreased catalytic
      activity or altered ligand binding. Our analysis reveals the putative effects of
      all known missense mutations in HNE, thus allowing the structural basis of cyclic
      and congenital neutropenia to be elucidated. We have employed and analyzed a set
      of some 30 different methods for predicting the effects of amino acid
      substitutions. We present results and experience from the analysis of the
      applicability of these methods in the analysis of numerous genes, proteins, and
      diseases to reveal protein structure-function relationships and disease genotype
      phenotype correlations.

PMID- 16986122
TI  - A common variant located in the 3'UTR of the RET gene is associated with
      protection from Hirschsprung disease.
AB  - Complex diseases are common genetic disorders showing familial aggregation but no
      typical Mendelian inheritance. Hirschsprung disease (HSCR), a developmental
      disorder characterized by the absence of enteric neurons in distal segments of
      the gut, shows a complex pattern of inheritance, with the RET protooncogene
      acting as a major gene and additional susceptibility loci playing minor roles. In
      the last years, we have identified a "protective" RET haplotype, which is
      underrepresented in HSCR patients with respect to controls. Here, we demonstrate
      that the protective effect of this haplotype is due to a variant located in the
      3' untranslated region (UTR) of the RET gene, which slows down the physiological
      mRNA decay of the gene transcripts. Such a functional effect of this common RET
      variant explains the under-representation of the whole haplotype and its role as
      a modifying factor in HSCR pathogenesis.

PMID- 16986123
TI  - Phase II study of temozolomide and thalidomide in patients with metastatic
      melanoma in the brain: high rate of thromboembolic events (CALGB 500102).
AB  - BACKGROUND: Preliminary studies suggesting that extended-dose temozolomide with
      thalidomide is safe and active in patients with metastatic melanoma have led to
      frequent use of this oral regimen. To confirm these observations the combination
      was tested in a multicenter Phase II trial in patients with melanoma brain
      metastases. METHODS: Eligible patients had melanoma brain metastases, with or
      without systemic metastases. The primary endpoint was response rate in brain
      metastases. Patients received temozolomide at a dose of 75 mg/m2/day for 6 weeks
      with a 2-week rest between cycles, and thalidomide (escalated to 400 mg/day for
      patients age < 70 years or to 200 mg/day for patients age > or = 70 years). A 2
      stage design required > or = 3 responses in the first 21 patients before
      enrolling 29 additional patients in the second stage. RESULTS: Sixteen eligible
      patients were enrolled. No objective responses were observed. The median survival
      was 23.9 weeks. Seven patients withdrew because of tumor progression; 7 were
      removed during Cycle 1 because of adverse events, including allergic reaction (1
      patient), severe fatigue (1 patient), sudden death (1 patient), and
      thromboembolic events (pulmonary embolism in 3 patients and deep vein thrombosis
      in 1 patient); 2 patients withdrew when the study was suspended and subsequently
      closed. No associations could be established between baseline characteristics and
      toxicity. CONCLUSIONS: The proportion of patients with lethal or potentially life
      threatening adverse events was high (0.31, 95% confidence interval, 0.11-0.59),
      and the absence of objective responses made it unlikely that further accrual
      would demonstrate the efficacy of the regimen. These observations provide little
      support for the use of this combination for melanoma brain metastases unless safe
      and effective methods to prevent thrombosis are developed.

PMID- 16986124
TI  - Prognostic stratification of patients with anaplastic gliomas according to
      genetic profile.
AB  - BACKGROUND: There is a need to improve the current, controversial, and poorly
      reproducible classification of anaplastic gliomas, which represent a highly
      heterogeneous entity in terms of survival. METHODS: The impact of the most common
      genetic alterations on survival was investigated based on 156 anaplastic gliomas:
      Among the patients who were included, the gender ratio was 1.32, the median age
      was 45.5 years (range, 20-83 years), and the median Karnofsky performance status
      was 70 (range, 40-100). Genetic analysis included a search for loss of
      heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p
      and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent
      kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression.
      RESULTS: The median survival was 33.5 months, and the median progression-free
      survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was
      correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q,
      amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on
      1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to
      EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR
      amplification and LOH on 10q. In a multivariate analysis, the significant
      prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A
      deletion. Recursive partitioning analysis (RPA) divided the whole group
      hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q
      codeletion (median survival, 98 months), Group B with EGFR amplification (median
      survival, 17 months), and Group CC (median survival, 31 months), providing a
      basis for a genetically based prognostic subclassification for patients with
      Grade III gliomas. CONCLUSIONS: The search for 1p19q codeletion and EGFR receptor
      amplification provides a simple, clinically relevant prognostic subclassification
      of grade III gliomas.

PMID- 16986125
TI  - Early effects of imatinib mesylate on the expression of insulin-like growth
      factor binding protein-3 and positron emission tomography in patients with
      gastrointestinal stromal tumor.
AB  - BACKGROUND: Imatinib has demonstrated marked clinical efficacy against
      gastrointestinal stromal tumor (GIST). Microarray technology, real-time
      polymerase chain reaction (PCR) validation, and fluorodeoxyglucose-positron
      emission tomography (FDG-PET) imaging were used to study the early molecular
      effects of imatinib antitumor activity in GIST. METHODS: After exposure of
      sensitive and resistant sarcoma cell lines to imatinib for 24 to 48 hours, the
      changes in gene expression were evaluated using a 1146 unique pathway array with
      Western blot validation. Real-time PCR was used to confirm changes in gene
      expression in human GIST samples (preimatinib biopsy and postimatinib surgical
      specimen after 3-7 days of therapy). FDG-PET was performed to correlate
      radiographic findings with the effects of imatinib on gene expression in GIST.
      RESULTS: In all, 55 genes demonstrated a > or = 2-fold change after imatinib
      treatment of the GIST882 cells. Among these genes there was up-regulation of
      insulin-like growth factor binding protein-3 (IGFBP-3), a protein that modulates
      proliferation and apoptosis. Western blot analysis confirmed the increase of
      IGFBP-3 only in imatinib-sensitive GIST882 cells. Up to a 7-fold induction (49%
      mean increase; P = .08) of IGFBP-3 mRNA was found in tumor samples from patients
      with low residual FDG uptake, whereas there was an up to 12-fold reduction (-102%
      mean decrease; P = .03) in IGFBP-3 in those patients with high residual FDG
      uptake after imatinib therapy. CONCLUSIONS: In the current study, imatinib
      appears to regulate numerous genes and specifically induces IGFBP-3 in GIST cells
      and tumor samples. IGFBP-3 levels also were found to be inversely correlated with
      residual FDG uptake in GIST patients early in imatinib therapy. These initial
      observations suggest that IGFBP-3 is an important early marker of antitumor
      activity of imatinib in GIST.

PMID- 16986126
TI  - The role of Src in solid and hematologic malignancies: development of new
      generation Src inhibitors.
AB  - c-Src was the first protooncogene described and was among the first molecules in
      which tyrosine kinase activity was documented. c-Src has been defined as a common
      modular structure that participates in much of the crosstalk between the
      cytoplasmic protein tyrosine kinases and tyrosine kinase receptors. Understanding
      the structure and function of this important class of protein kinases and
      elucidating the molecular signaling events mediated by c-Src are important not
      only for identifying the critical pathways but also for designing new strategies
      to block or inhibit the action of these kinases. Despite the large amount of
      information available on c-Src, its precise functions in cancer remain to be
      elucidated. Recently, there has been renewed interest in c-Src as a molecular
      target for cancer therapy, and multiple c-Src inhibitors are entering clinical
      trials. In this review, the authors describe the function and expression of c-Src
      in human malignancies and the novel c-Src inhibitors and their potential
      applications for cancer treatment.

PMID- 16986127
TI  - Methemoglobin--it's not just blue: a concise review.
AB  - Hemoglobin has functions besides carrying oxygen to the tissues, and regulates
      vascular tone and inflammation via a redox couple with methemoglobin. Hemoglobin
      has iron in the reduced valance Fe(II) and methemoglobin has iron in the oxidized
      valance Fe (III), with a free energy capable of producing water from oxygen. In
      generating methemoglobin the couple functions as a nitrite reductase. The degree
      of oxidation of hemoglobin senses the oxygen level in the blood and uses its
      ability to produce nitric oxide from nitrite to control vascular tone, increasing
      blood flood when the proportion of oxygenated hemoglobin falls. Additional
      cardiovascular damage is produced by methemoglobin mediated oxidation of light
      density lipoproteins, accelerating arteriosclerosis. In addition, the release of
      heme from methemoglobin is an important factor in inflammation. These physiologic
      functions are paralleled by the well-described role in the oxidation of various
      drugs resulting in methemoglobinemia.

PMID- 16986128
TI  - Unrelated donor bone marrow transplantation using a chemotherapy-only preparative
      regimen for adults with high-risk acute myelogenous leukemia.
AB  - Limited data are available for adults undergoing unrelated donor (URD) BMT for
      AML using chemotherapy-only preparative regimens. Previous studies incorporated
      irradiation, included adults and children, and excluded secondary leukemia.
      Herein we report long-term outcomes for adults with poor-prognostic AML receiving
      a novel regimen of busulfan (16 mg/kg), cytarabine (8,000 mg/m(2)), and
      cyclophosphamide (120 mg/kg) (BAC), followed by URD BMT. From June 1995 through
      October 2001, 45 adults were enrolled. Adverse features included unfavorable
      cytogenetics (49%), secondary AML (47%), leukemia at transplant (42%), and
      extramedullary disease (16%). At time of BMT, 23 were in remission (12 CR1) while
      22 had leukemia. Four (9%) died early. Acute and chronic GVHD rates were 44 and
      67%, respectively. Seventeen (38%) were disease-free 52 months post-BMT; 13 were
      leukemia-free (eight CR1) at transplant. Eleven relapsed. Three-year DFS and OS
      were 42 and 46%, respectively. DFS and OS were longer, and relapses less, for
      those in CR at time of BMT. Secondary leukemia, cytogenetics, cell dose, and GVHD
      did not influence outcome. In poor-risk AML, BAC provided cytoreduction
      comparable to reported TBI-containing regimens, when administered for URD BMT.
      With decreasing treatment-related mortality, it is justified to proceed early to
      URD BMT for patients with poor prognostic features.

PMID- 16986129
TI  - Predictable prognostic factor of CD56 expression in patients with acute myeloid
      leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem
      cell transplantation.
AB  - CD56 expression in acute myeloid leukemia (AML) has been associated with
      extramedullary leukemia and multidrug resistance, but its clinical and prognostic
      significance has not been clearly identified. This study examined CD56 expression
      in 37 adult de novo AML patients with t(8:21). CD56 was expressed in 25 cases
      (67.6%). Complete remission (CR) rates were similar in both groups (91.7% vs.
      88.7%; P = 0.73), but the relapse rates differed considerably (60% vs. 25%; P =
      0.02). The median duration of disease-free survival (DFS) was significantly
      shorter in the CD56+ (median, 12.2 +/- 6.4 months) than in the CD56- group
      (median, not reached) (P = 0.02). In addition, the median duration of survival
      differed significantly in the CD56+ group (median, 14.9 +/- 4.4 months) compared
      with the CD56- group (median, not reached) (P = 0.01). Of the fifteen
      transplanted patients who achieved CR, allogeneic HST was performed from their
      siblings. The median duration of DFS in the CD56+ patients was significantly
      shorter than the CD56- patients (median, 24.4 +/- 4.5 months vs. median, not
      reached; P = 0.02). We concluded that CD56 expression correlates to a reduced DFS
      and survival for AML patients with t(8:21), including those patients who
      underwent transplantation.

PMID- 16986130
TI  - Acquired von Willebrand syndrome: diagnostic problems and therapeutic options.
AB  - We present a case of acquired von Willebrand syndrome (AVWS) due to a monoclonal
      gammopathy of undetermined significance. Initially this case was diagnosed as
      congenital von Willebrand disease (VWD); however, re-examination of the medical
      history rendered a congenital bleeding disorder unlikely. A normal plasma von
      Willebrand factor (VWF) propeptide level and a very short half-life of VWF after
      a test infusion with factor VIII/VWF concentrate confirmed the diagnosis AVWS.
      Two major surgical procedures were successfully managed using high-dose
      intravenous immunoglobulin. The differential diagnosis with congenital VWD and
      the diagnostic and therapeutic approaches of AVWS are discussed. We conclude that
      the diagnosis of AVWS relies primarily on clinical suspicion and a careful
      bleeding history. A correct diagnosis is essential for optimal perioperative
      management and treatment of bleeding episodes.

PMID- 16986131
TI  - Physical fitness indices and anthropometrics profiles in schoolchildren with
      sickle cell trait/disease.
AB  - The current studies aimed at determining physical fitness indices and
      anthropometrics profiles of school children with sickle cell trait (SCT) and
      sickle cell disease (SCD). Male school children (150) comprising 3 Groups
      participated in the studies. Group 1 has 50 normal healthy controls, while Groups
      2 and 3 each has 50 children who were suffering from SCT and SCD, respectively.
      Anthropometrics measurement and parameters of physical fitness were assessed in
      all subjects. All children were also subjected to a 5-min running exercise test
      on a flat motorized treadmill at speed corresponding to 5 km/hr. Throughout the
      test, heart rate was monitored and recorded during exercise and for 10-min during
      recovery. Blood lactate was measured before and 5 min following the completion of
      test. The mean values of lean body mass and height were lower in the SCD children
      (P < 0.05) compared with the healthy subjects and SCT individuals. Children with
      SCD exhibited a higher mean value (P < 0.05) for percent body fat and fat mass
      than the normal healthy subjects and SCT individuals. Although all groups
      tolerated well the treadmill exercise protocol, the SCD group exhibited higher (P
      < 0.05) mean values of heart rate during exercise than those observed in the SCT
      and normal control children. In addition, SCD children showed higher serum
      lactate values before and after treadmill exercise compared to the other groups.
      Children with SCD exhibit high level of adiposity; low level of fitness and their
      exercise performance appears to be physiologically more stressful as indicated by
      heart rate and blood lactate concentration responses.

PMID- 16986132
TI  - Concurrent immune thrombocytopenic purpura and Guillain-Barre syndrome in a
      patient with Hashimoto's thyroiditis.
AB  - Immune thrombocytopenic purpura (ITP), Guillain-Barre syndrome (GBS), and
      Hashimoto's thyroiditis (HT) are autoimmune disorders caused by impaired self
      tolerance mechanisms triggered by interaction between genetic and environmental
      factors. ITP is an immune-mediated destruction of platelets resulting in
      mucocutaneous bleeding, GBS is an ascending motor paralysis caused by an
      inflammatory demyelination of peripheral nerves, and HT is characterized by
      autoimmune-mediated destruction of the thyroid gland. The concurrent development
      of ITP and GBS has only rarely been reported in the literature, and GBS itself
      rarely occurs with other autoimmune disorders. We present a 21 year-old patient
      with known Hashimoto's hypothyroidism that simultaneously developed GBS and ITP
      after an upper respiratory tract infection. To the best of our knowledge, this is
      the first reported case of these three autoimmune disorders in the same patient.
      This points to a possible common genetic predisposition to these disorders.

PMID- 16986133
TI  - Platelet functional implications of glycoprotein Ibalpha polymorphisms in African
      Americans.
AB  - The platelet glycoprotein Ibalpha is crucial in the binding of platelets to Von
      Willebrand Factor within areas of high stress. A single nucleotide polymorphism
      of GP Ibalpha gives rise to the Ko(a) (HPA-2b) and the -5C Kozak polymorphism.
      The presence of these polymorphisms has been associated with an increased risk
      for atherothrombotic disease. The Ko(a) polymorphism has been shown to have a
      higher prevalence in African Americans compared to American Caucasians. However,
      very little is known regarding any functional consequences of these platelet
      polymorphisms in African Americans. We assessed the prevalence of the Ko and -5C
      Kozak polymorphisms in a population of both African American and American
      Caucasian patients with and without CAD and determined whether there were
      platelet functional consequences in both groups. We studied 99 patients of which
      22 were African American and 77 were American Caucasian. Aggregations were
      performed and shear induced platelet plug formation was tested using a platelet
      function analyzer. The HPA-2b allele was significantly higher in African
      Americans when compared to Caucasians (P = 0.001). Genotype frequencies of the 
      5C Kozak polymorphism were not significantly different between the two groups. We
      found no differences in platelet aggregation in African Americans who were either
      heterozygous or homozygous for the HPA-2b allele or the -5C Kozak allele when
      compared to American Caucasians of the same category. We found no significant
      differences in PFA-100 testing. We conclude from our study that these
      polymorphisms do not lead to altered platelet function in African Americans.

PMID- 16986134
TI  - Hypocupremia associated with prior vitamin B12 deficiency.
AB  - Clinical similarities between vitamin B(12) and copper deficiencies prompted us
      to investigate if hypocupremia is present in patients receiving vitamin B(12)
      supplementation. Our pilot study results indicate that a significant number of
      elderly patients with prior diagnosis of vitamin B(12) deficiency have also
      undiagnosed hypocupremia.

PMID- 16986135
TI  - Early proactive management improves upper urinary tract function and reduces the
      need for surgery in patients with myelomeningocele.
AB  - AIMS: To investigate whether upper urinary tract function and the need for
      surgery in patients with myelomeningocele depends on the timing of initiating
      neurourological management. PATIENTS AND METHODS: One hundred thirty-three
      patients with myelomeningocele were included in our retrospective study. The
      patients were divided based on age at the initial evaluation into three
      categories: from day of birth to age 2 (group 1, n = 67), from age 3 to age 10
      (group 2, n = 44), and after age 10 (group 3, n = 22). Upper urinary tract
      function and the need for surgery with the intention to preserve or normalize the
      upper urinary tract function were compared between the three groups. RESULTS:
      Mean follow-up was 11, 10, and 9 years in group 1, 2, and 3, respectively. The
      upper urinary tract function was normal in 91%, 80%, and 82% at the initial
      evaluation (P = 0.194) and in 99%, 86%, and 86% at the last follow-up (P = 0.012)
      in group 1, 2, and 3, respectively. Following failure of conservative therapy
      only, the proportions of patients undergoing surgical interventions with the
      intention to preserve or normalize the upper urinary tract function was
      significantly (P = 0.0002) different among the three groups: 15%, 34%, and 59%,
      respectively. CONCLUSIONS: Early proactive management improves upper urinary
      tract function and reduces the need for surgery in patients with myelomeningocele
      in the long-term. Therefore, initiation of proactive neurourological management
      as early as possible, ideally from the day of birth, is strongly recommended.

PMID- 16986136
TI  - Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor
      overactivity: a double blind controlled randomized study.
AB  - AIMS: Many studies report the use of alcoholic capsaicin instillation to treat
      neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) and multiple
      sclerosis (MS) patients. However, poor tolerability due to the irritative effect
      of the ethanol solvent limits its use. Our study aimed to evaluate the efficacy
      and tolerability of a new formulation of capsaicin in a glucidic solution in a
      multicenter clinical trial. MATERIALS AND METHODS: Thirty-three patients
      (26MS/7SCI) suffering from urinary incontinence due to refractory NDO were
      prospectively enrolled in a double-blind placebo controlled study and randomized
      to capsaicin group (CG, N = 17) or solvent group (SG, N = 16). They respectively
      received an intravesical instillation of 100 ml capsaicin diluted in glucidic
      solvent (CG) or glucidic solvent alone (SG). Efficacy (voiding chart, maximum
      cystometric capacity (MCC)) and tolerability were evaluated on days 0 (D0), 30
      and 90. RESULTS: On D0, groups were homogeneous. On D30, significant improvement
      of overactive bladder syndrome and an increase in MCC were shown in CG, whereas
      there were no improvement in SG. No significant improvement was shown on D90 in
      both groups. There were no significant differences between groups regarding
      prevalence, duration, or intensity of side effects, except for short duration
      pubic pain during instillation more often reported in CG (58.8%) than in SG
      (12.5%) (P < 0.01). CONCLUSION: This placebo controlled study using glucidic
      capsaicin confirms its short-term efficacy in NDO patients. Global tolerance of
      glucidic capsaicin appeared satisfactory. Long-term efficacy and tolerance of
      repeated glucidic capsaicin instillations need to be evaluated.

PMID- 16986137
TI  - Bladder sensation in peripheral nerve lesions.
AB  - OBJECTIVE: To present bladder sensory data of three common peripheral nerve
      lesions (e.g., distal, intermediate/focal, and proximal). METHODS: We measured
      first sensation (FS) and bladder capacity (BC) (not exceeding 600 ml) in 71
      patients with peripheral nerve lesions: 35 diabetic neuropathy (D group), 6 post
      pelvic surgery (S), and 27 cauda equina syndrome due to lumbar spondylosis (L).
      We excluded those with detrusor overactivity or low compliance that might affect
      bladder sensation. RESULTS: The mean FS was 301.7 ml (D), 271.3 ml (S), and 189.4
      ml (L), with the largest being in the D group (P < 0.05); the mean BC was 495.2,
      475.4, and 391.4 ml, with the largest being in the D group (P < 0.05); who
      commonly had less frequent toileting. The mean post-void residual volume was
      106.5, 29.0, and 42.0 ml; the values tended to increase along with BC. In the D
      group, the mean FS in patients with skin hypoalgesia as detected by pin prick and
      in those without it was 407.8 and 210.0 ml. The percentage of patients with FS <
      100 ml was 5.7%, 0%, and 7.4%, respectively, who commonly had urinary urgency and
      frequency. CONCLUSIONS: Bladder sensation is affected in diabetic neuropathy more
      severely than in intermediate/proximal lesions, together with somatic sensory
      disturbance. Bladder sensory disturbance leads to less frequent toileting,
      resulting in bladder over-distension and large post-void residuals. A small
      proportion of patients with peripheral nerve lesions develop urinary urgency,
      presumably reflecting irritation of the afferent nerve fibers or the urothelium.

PMID- 16986139
TI  - Sociotropy-autonomy and interpersonal problems.
AB  - Sociotropy and autonomy are conceptualized as two personality dimensions that
      relate to an individual's vulnerability to depression. Sociotropy is
      characterized as an excessive investment in interpersonal relationships, and
      autonomy is characterized as an excessive concern with personal achievement and
      control. This study examined the relationships between sociotropy and autonomy,
      and a variety of interpersonal problems with close and nonclose others. Results
      suggested that sociotropic individuals are overly nurturant to nonclose others
      but vindictive to individuals who are close to them. In contrast, autonomous
      individuals were found to be domineering to nonclose others but socially avoidant
      toward people close to them. These findings are discussed in the context of
      recent research regarding the interpersonal patterns associated with sociotropy
      and autonomy.

PMID- 16986138
TI  - Cytoskeletal asymmetry in Zea mays subsidiary cell mother cells: a monopolar
      prophase microtubule half-spindle anchors the nucleus to its polar position.
AB  - Double labeling of microtubules and actin filaments revealed that in prophase
      subsidiary mother cells of Zea mays a monopolar prophase microtubule "half
      spindle" is formed, which lines the nuclear hemisphere distal to the inducing
      guard mother cell. The nuclear hemisphere proximal to the guard mother cell is
      lined by an F-actin cap, consisting of a cortical F-actin patch and actin
      filaments originating from it. The microtubules of the "half-spindle" decline
      from the nuclear surface and terminate to the preprophase microtubule band. After
      disintegration of the latter, a bipolar metaphase spindle is organized. The polar
      F-actin cap persists during mitosis and early cytokinesis, extending to the
      chromosomes and the subsidiary cell daughter nucleus. In oryzalin treated
      subsidiary mother cells the prophase nuclei move away from the polar site.
      Cytochalasin B and latrunculin-B block the polar migration of subsidiary mother
      cell nuclei, but do not affect those already settled to the polar position. The
      prophase nuclei of latrunculin-B treated subsidiary mother cells are globally
      surrounded by microtubules, while the division plane of latrunculin-B treated
      subsidiary mother cells is misaligned. The prophase nuclei of brick 1 mutant Zea
      mays subsidiary mother cells without F-actin patch are also globally surrounded
      by microtubules. The presented data show that the prophase microtubule "half
      spindle"-preprophase band complex anchors the subsidiary mother cell nucleus to
      the polar cell site, while the polar F-actin cap stabilizes the one metaphase
      spindle pole proximal to the inducing guard mother cell.

PMID- 16986140
TI  - Linear systems analysis of the ciliary steering behavior associated with negative
      phototaxis in Chlamydomonas reinhardtii.
AB  - In response to light stimulation Chlamydomonas reinhardtii changes the beating
      frequency, beating pattern, and beating synchrony of the trans and cis cilia to
      steer the freely-swimming cell relative to light sources. To understand the cell
      steering behavior the impulse responses of the beating frequency and stroke
      velocity of each cilium have been obtained with high temporal resolution on cells
      held with a micropipette. Interestingly the response of each cilium is quite
      different. The trans cilium responds with less delay than the cis cilium for both
      beating frequency and stroke velocity. For light stimulation at 2 Hz, the
      critical cell-rotation frequency, both responses of the trans and cis cilia are
      about 180 degrees out of phase. The trans-cilium beating frequency response peaks
      at a stimulus frequency of 5-6 Hz, higher than the cis at 1-2 Hz. The stroke
      velocities of the trans and cis cilia have the same stimulus-frequency response
      (2 Hz), but the trans cilium has a shorter delay than the cis. The times to
      maximum response are much shorter than the time for a rotation of the cell. The
      use of two different approaches that enable the trans cilium to respond ahead of
      the cis for both the beating frequency and stroke velocity responses suggests the
      importance of both responses to phototaxis. Internal cell processing responsible
      for the time course of the responses is proposed.

PMID- 16986141
TI  - Assembling microtubules disintegrate the postsynaptic density in vitro.
AB  - The postsynaptic density (PSD), a disk-shaped protein aggregation of several
      hundred nm in diameter, plays important roles in the signal transduction and
      molecular organization of the excitatory synapses in mammalian CNS. The PSD
      resides in the microfilament-enriched cytoplasm of dendritic spines where the
      transient appearance of microtubules has been reported. When PSD isolated from
      porcine brain was incubated with polymerizing alpha,beta-tubulins, its turbidity
      became greater than that of the original PSD, suggesting that the PSD's structure
      was altered upon incubating with assembling microtubules. By transmission
      electron microscopy, smaller PSD fragments and several novel structures,
      including holes and finger-like extensions, were found in the PSD after
      incubation with assembling microtubules, but not in the original PSD or in the
      PSD incubated with alpha,beta-tubulins pretreated with vincristine. The results
      suggest that the interactions with assembling microtubules may result in the
      formation of holes in the PSD, and the rupture of these holes subsequently leads
      to the formation of smaller PSD fragments.

PMID- 16986142
TI  - A new approach to study fibroblast migration.
AB  - This paper presents a new approach to study cell migration. Human tendon
      fibroblasts were plated on silicone membranes coated with 10 microg/ml ProNectin
      F. The silicone surfaces were micro-fabricated with parallel microgrooves, with
      10 microm ridge and groove width, and 3 microm groove depth. Fibroblasts grown in
      the microgrooves had an elongated shape and oriented along the microgroove
      direction. They also moved along the same direction instead of "random walk" when
      cells migrate on smooth culture surfaces. In response to TGF-beta1 (5 ng/ml)
      treatment, these fibroblasts on the microgrooved surfaces were differentiated
      into myofibroblasts, as judged by an elevated expression of alpha-smooth muscle
      actin (alpha-SMA), a specific marker for myofibroblasts. Moreover, these
      myofibroblasts were found to be approximately 30% less motile compared to that of
      untreated fibroblasts. Thus, use of microgrooved surface may be an effective
      approach to detect difference in cell motility because cell migration on the
      microgrooved surface is one dimensional and hence easier to be quantified than
      two-dimensional random movement on conventional smooth culture surfaces.

PMID- 16986143
TI  - Individualized assessment of quality of life in idiopathic Parkinson's disease.
AB  - The purpose of this study was to assess quality of life (QoL) of patients with
      idiopathic Parkinson's disease (IPD). The Parkinson's Disease Questionnaire (PDQ
      39) was compared with an individualized QoL tool: the Schedule for Evaluation of
      Individual Quality of Life Direct Weighting (SEIQoL-DW). One hundred twenty-three
      patients underwent interviews using these tools, together with the Mini Mental
      State examination, Beck Depression Inventory, a qualitative pain assessment, and
      the Palliative Care Assessment tool (for symptoms). The SEIQoL-DW was well
      tolerated and demonstrated that QoL not only was broad and highly individualistic
      but also was determined more by psychosocial than physical issues. Of the 87
      domains nominated by patients, the most common were family (87.8%), health
      (52.8%), leisure activities (36.6%), marriage (35%), and friends (30.9%). The
      SEIQoL index score was predicted by depression but not by disease stage. However,
      the PDQ-39 was predicted by disease stage, the number of symptoms, and
      depression. Direct comparison of the tools confirmed that the SEIQoL index score
      was predicted by the PDQ-39 domains of social support, cognitive impairment, and
      emotion. The use of the SEIQoL-DW challenges current thinking within IPD research
      regarding QoL and its assessment using the PDQ-39.

PMID- 16986144
TI  - The difficulty with experience: does practice increase susceptibility to
      premature closure?
AB  - INTRODUCTION: A recent review of the physician performance literature concluded
      that the risk of prematurely closing one's diagnostic search increases with years
      of experience. To minimize confounding variables and gain insight into cognitive
      issues relevant to continuing education, the current study was performed to test
      this conclusion. METHODS: Physician participants were shown a series of case
      histories and asked to judge the probability of a pair of diagnoses. The order in
      which features were presented was manipulated across participants and the
      probabilities compared to determine the impact of information order. Two groups
      of participants were recruited, 1 older than and 1 younger than 60 years.
      RESULTS: The probability assigned to a diagnosis tended to be greater when
      features consistent with that diagnosis preceded those consistent with an
      alternative than when the same features followed those consistent with the
      alternative. Older participants revealed a greater primacy effect than less
      experienced participants across 4 experimental conditions. DISCUSSION: Physicians
      with greater experience appear to weigh their first impressions more heavily than
      those with less experience. Educators should design instructional activities that
      account for experience-specific cognitive tendencies.

PMID- 16986145
TI  - Effectiveness of an enhanced peer assessment program: introducing education into
      regulatory assessment.
AB  - INTRODUCTION: The College of Physicians and Surgeons of Ontario developed an
      enhanced peer assessment (EPA), the goal of which was to provide participating
      physicians educational value by helping them identify specific learning needs and
      aligning the assessment process with the principles of continuing education and
      professional development. In this article, we examine the educational value of
      the EPA and whether physicians will change their practice as a result of the
      recommendations received during the assessment. METHODS: A group of 41 randomly
      selected physicians (23 general or family practitioners, 7 obstetrician
      gynecologists, and 11 general surgeons) agreed to participate in the EPA pilot.
      Nine experienced peer assessors were trained in the principles of knowledge
      translation and the use of practice resources (tool kits) and clinical practice
      guidelines. The EPA was evaluated through the use of a postassessment
      questionnaire and focus groups. RESULTS: The physicians felt that the EPA was
      fair and educationally valuable. Most focus group participants indicated that
      they implemented recommendations made by the assessor and made changes to some
      aspect of their practice. The physicians' suggestions for improvement included
      expanding the assessment beyond the current medical record review and interview
      format (eg, to include multisource feedback), having assessments occur at regular
      intervals (eg, every 5 to 10 years), and improving the administrative process by
      which physicians apply for educational credit for EPA activities. CONCLUSIONS:
      The EPA pilot study has demonstrated that providing detailed individualized
      feedback and optimizing the one-to-one interaction between assessors and
      physicians is a promising method for changing physician behavior. The college has
      started the process of aligning all its peer assessments with the principles of
      continuing professional development outlined in the EPA model.

PMID- 16986146
TI  - Clinical teachers' attitudes toward the efficacy of evidence-based medicine
      workshop and self-reported ability in evidence-based practice in Iran.
AB  - INTRODUCTION: Evidence-based medicine (EBM) has been introduced in medical
      schools worldwide, but there is little known about effective methods for teaching
      EBM skills, particularly in developing countries. This study assesses the impact
      of an EBM workshop on clinical teachers' attitudes and use of EBM skills.
      METHODS: Seventy-two clinical teachers attended two half-day workshops on EBM.
      Participants completed precourse and postcourse questionnaires using a 5-point
      Likert scale. Nonparametric 2-sample Wilcoxon rank-sum tests were performed to
      compare responses. RESULTS: Attitudes about EBM improved (3.2 precourse vs 3.4
      postcourse), as did self-reported EBM skills (3.1 vs 4.4, p < .0001). DISCUSSION:
      An EBM workshop may improve clinical teachers' abilities and skills in using EBM.
      However, carefully designed studies are required to evaluate the long-term
      effects of EBM curricula in changing behaviors, practice patterns, and patient
      care outcomes.

PMID- 16986147
TI  - Professional isolation and performance assessment in New Zealand.
AB  - INTRODUCTION: Solo and nonurban practice, nonmembership of a professional group,
      and aging are all associated with underperformance and may be indicators of
      professional isolation. Although it may lead to underperformance in physicians,
      there are no clear measures to assess professional isolation. METHODS: By mailed
      questionnaire, experienced performance assessors were asked to list markers of
      professional isolation. RESULTS: A set of criteria and descriptors for
      professional isolation was generated, and included personality; solo practice;
      poor colleague relationships; outlier practice; MOPS or CPD failure; specialist
      in only private practice; stress, no relief, complaints, job dissatisfaction;
      locum, itinerant or part-time practice; cultural barriers; male gender.
      DISCUSSION: The identification of physicians at risk for professional isolation
      may enable the prevention of poor performance.

PMID- 16986148
TI  - Research to practice in The Journal of Continuing Education in the Health
      Professions: a thematic analysis of volumes 1 through 24.
AB  - INTRODUCTION: Authors have stressed the importance of the broader contextual
      influences on practice improvement and learning and have expressed concern about
      gaps between research and practice. This implies a potential expansion of the
      knowledge base for continuing education in the health professions (CEHP) and an
      increased emphasis on research evidence for that knowledge. How has the content
      of The Journal of Continuing Education in the Health Professions (JCEHP)
      reflected those changes? What are the implications for CEHP practitioners?
      METHODS: Based on all abstracts, tables of contents, and editorials, a thematic
      analysis was completed for volumes 1 through 24 of JCEHP. All texts were
      downloaded into qualitative analysis software and coded. Main code categories
      included demographics of articles, concepts relating to CEHP as a discipline,
      knowledge translation and outcomes-oriented continuing education, and theories
      and frameworks. Key themes were identified. RESULTS: Key themes include
      categories of topics included in JCEHP over the years, the increased prominence
      of research in JCEHP, a dual research evidence-to-practice gap, the
      professionalization of continuing education providers, and interdisciplinarity
      and the links with broader frameworks that have been proposed for CEHP.
      DISCUSSION: Two sets of research-to-practice gaps are portrayed in the journal:
      the gap between clinical research and practice and the gap between research and
      practice in CEHP. To close the first gap, authors have asserted that the second
      gap must be addressed, ensuring that CEHP practices themselves are evidence
      based, driven by theory-based research. This is a variation on prior debates
      regarding the need to define CEHP as a discipline, which uses the language of
      professionalization. The increased focus of continuing education on the contexts
      of health care providers' practices has multiplied the topics that are
      potentially relevant to CEHP practice.

PMID- 16986149
TI  - The prevalence and special educational requirements of dyscompetent physicians.
AB  - Underperformance among physicians is not well studied or defined; yet, the
      identification and remediation of physicians who are not performing up to
      acceptable standards is central to quality care and patient safety. Methods for
      estimating the prevalence of dyscompetence include evaluating available data on
      medical errors, malpractice claims, disciplinary actions, quality control
      studies, medical record review studies, and in-stream assessments of physician
      performance. These data provide a range of estimates from 0.6% to 50%, depending
      on the method. A reasonable estimate of dyscompetence appears to be 6% to 12%.
      Age-related cognitive decline, impairment due to substance use disorders, and
      other psychiatric illness can contribute to underperformance, diminishing
      physicians' insight into their level of performance as well as their ability to
      benefit from an educational experience.Currently, dyscompetent physicians in the
      United States are identified through either the legal system or peer review. The
      primary method of resolving issues of underperformance in physicians is through
      continuing medical education (CME). Although a number of specialized assessment
      and education programs exist in the United States, these programs are largely
      underutilized. Similar programs exist in Canada and have provided evidence of the
      efficacy of a more specialized and individualized educational approach for
      underperforming physicians. Current specialty programs focused on this population
      employ individual assessments of knowledge and performance, individually designed
      educational programs, long-term plans for maintenance of educational activity,
      and repeated assessment of performance level. Noting that few CME programs offer
      these requirements, a number of changes to current medical quality assurance
      programs that might foster such educational requirements for underperforming
      physicians are provided.

PMID- 16986150
TI  - Long working hours, occupational health and the changing nature of work
      organization.
AB  - BACKGROUND: The impact of long working hours on health has been of major concern
      since the late 19th Century. Working hours are again increasing in the US.
      METHODS: An overview of historical, sociological, and health-related research
      presented at an international conference on long working hours is discussed as an
      introduction to a special section in this issue. RESULTS: Research indicates that
      long working hours are polarizing along class lines with professionals working
      regular though longer hours and less well-educated workers having fewer though
      more irregular hours. Extended and irregular hours are associated with acute
      reactions such as stress and fatigue, adverse health behavior such as smoking,
      and chronic outcomes such as cardiovascular and musculoskeletal disorders.
      CONCLUSIONS: Improved methodologies are needed to track exposure to long working
      hours and irregular shifts longitudinally. Research should focus on the adverse
      impact that sleep-deprived and stressed workers may have on the health of the
      public they serve. A variety of protective efforts should be undertaken and
      evaluated.

PMID- 16986153
TI  - A model of teaching-learning transactions in generalist-specialist consultations.
AB  - INTRODUCTION: A new paradigm in continuing medical education is characterized by
      emphasis on physicians' learning in practice. Consistent with this paradigm, our
      study examined a subset of clinical practice--generalist-specialist consultations
      -from an educational perspective. METHODS: We applied the grounded-theory method
      with semistructured interviews. Ten primary care physicians and 9 internal
      medicine subspecialists were interviewed regarding their approaches to learning
      and teaching during generalist-specialist consultations. RESULTS: Based on 48
      formal and informal consultations reported by physicians, we developed a theory
      of teaching-learning transactions in generalist-specialist consultations.
      DISCUSSION: As a teaching-learning transaction, the mutual learning process in
      generalist-specialist consultations involves 3 components: needs assessment,
      dialogue, and sufficiency. Providers of continuing medical education may use the
      proposed theoretical framework to help clinicians and health care organizations
      analyze and enhance educationally valuable interactions at the interface of
      primary and secondary care.

PMID- 16986154
TI  - Improving adherence to hand hygiene among health care workers.
AB  - Increased adherence to hand hygiene is widely acknowledged to be the most
      important way of reducing infections in health care facilities. Despite evidence
      of benefit, adherence to hand hygiene among health care professionals remains
      low. Several behavioral and organizational theories have been proposed to explain
      this. As a whole, the success of interventions to improve adherence to hand
      hygiene among health care professionals has been limited. Recent data suggest
      that a multifaceted intervention, including the use of feedback, education, the
      introduction of alcohol-based hand wash, and visual reminders, may increase
      adherence to hand-hygiene recommendations. Although the "active ingredient" of
      such an intervention is unknown, there is evidence that the use of feedback may
      be the key to increasing adherence. In this article, we review the theoretical
      basis for interventions and provide an overview of the evidence for
      interventions. Coherent and methodologically sound research is required to better
      understand the factors contributing to hand-hygiene behavior among health care
      professionals.

PMID- 16986156
TI  - Effects of transcutaneous electrical nerve stimulation on motor cortex
      excitability in writer's cramp: neurophysiological and clinical correlations.
AB  - We recently reported that transcutaneous electrical nerve stimulation (TENS)
      applied over forearm flexor muscles, a paradigm producing in physiological
      conditions transient changes in corticomotoneuronal excitability of forearm
      muscles, may improve motor symptoms in writer's cramp (WC). In the present study,
      we explored the possibility that one or repeated sessions of TENS might have
      beneficial effects on handwriting in WC by remodulating cortical excitability of
      forearm agonist and antagonist muscles. Motor evoked potentials (MEPs) after
      transcranial magnetic stimulation of the left motor cortex were recorded from the
      right flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles,
      before and after 1 and 15 sessions of TENS applied over flexor muscles in
      patients and in a control group. One session of TENS induced a significant
      smaller reduction of MEPs from the FCR and a smaller increase of the MEPs from
      the ECR in patients than in normal subjects. In WC, repeated sessions of TENS had
      the effect to decrease MEP amplitude in the FCR and to increase it in the ECR.
      This modulation was paralleled by a handwriting improvement. In conclusion,
      repeated TENS sessions may have the effect to re-modulate excitability of the
      motor cortex in WC and this modulation might partially play a role in temporarily
      improving the handwriting.

PMID- 16986157
TI  - Donepezil also effective in the treatment of Tourette's syndrome?

PMID- 16986158
TI  - Tetrabenazine for hyperglycemic-induced hemichorea-hemiballismus.
AB  - We reported a 74-year-old woman with new-onset diabetes mellitus who presented
      with the sudden onset of mild left hemiparesis and marked left hemichorea
      hemiballismus. Brain CT scan and MRI showed T1W, T2W, and DWI lesions in the
      right putamen and caudate, which have been previously reported in cases of
      hyperglycemic-induced hemichorea-hemiballismus (HIHH). The patient dramatically
      responded to tetrabenazine within a day. Subsequent dose reductions lead to a
      reemergence of symptoms. Tetrabenazine improves a variety of hyperkinetic
      movement disorders but, to our knowledge, its use has never been reported for
      HIHH.

PMID- 16986159
TI  - Camptocormia induced by atypical antipsychotics and resolved by electroconvulsive
      therapy.
AB  - We present a depressive patient who developed mild parkinsonian signs and
      camptocormia after the introduction of olanzapine. She had been treated before
      with other antipsychotic drugs. When camptocormia was diagnosed, olanzapine was
      withdrawn and levodopa was introduced. Depressive symptoms got worse and
      electroconvulsive therapy was tried. When the treatment was completed, her
      depression substantially improved and her posture became completely upright.

PMID- 16986160
TI  - Testing untyped alleles (TUNA)-applications to genome-wide association studies.
AB  - The large number of tests performed in analyzing data from genome-wide
      association studies has a large impact on the power of detecting risk variants,
      and analytic strategies specifying the optimal set of hypotheses to be tested are
      necessary. We propose a genome-wide strategy that is based on one degree of
      freedom tests for all the genotyped variants, and for all the untyped variants
      for which there is sufficient information in the observed data. The set of
      untyped variants to be tested is found using multi-locus measures of linkage
      disequilibrium and haplotype frequencies from a reference database such as HapMap
      (The International HapMap Consortium [2003] Nature 426:789-796). We introduce a
      novel statistic for testing differences in allele frequencies for untyped
      variation that is based on linear combinations of estimable haplotype
      frequencies. Algorithms for finding the sets of genotyped markers to be used in
      testing an untyped allele, and ways of incorporating haplotypes observed in the
      study data but not in the reference database are also described. The proposed
      testing strategy can be used as the first step in the analysis of genome-wide
      association data, and, because every performed test is directed to a marker, it
      can be used to specify the set of polymorphisms to genotype in follow-up studies.
      The described methodology provides also a tool for joint analysis of data from
      studies done on different platforms.

PMID- 16986161
TI  - The admixture maximum likelihood test: a novel experiment-wise test of
      association between disease and multiple SNPs.
AB  - Disease association studies often test large numbers of markers, and various
      methods have been proposed to correct for multiple testing. In this paper, we
      propose an admixture maximum likelihood approach that estimates both the
      proportion of associated single nucleotide polymorphisms (SNPs) and their typical
      effect size. We assessed this method and compared it with several previously
      proposed approaches by simulation. The maximum likelihood approach performed
      similarly to or better than all other tests across a wide range of alternative
      hypotheses. The rank truncated product method also had good power, though
      somewhat inferior to the maximum likelihood approach in most cases. A simple
      Bonferroni correction performed best only when the number of associated SNPs was
      small.

PMID- 16986162
TI  - Imputation methods to improve inference in SNP association studies.
AB  - Missing single nucleotide polymorphisms (SNPs) are quite common in genetic
      association studies. Subjects with missing SNPs are often discarded in analyses,
      which may seriously undermine the inference of SNP-disease association. In this
      article, we develop two haplotype-based imputation approaches and one tree-based
      imputation approach for association studies. The emphasis is to evaluate the
      impact of imputation on parameter estimation, compared to the standard practice
      of ignoring missing data. Haplotype-based approaches build on haplotype
      reconstruction by the expectation-maximization (EM) algorithm or a weighted EM
      (WEM) algorithm, depending on whether case-control status is taken into account.
      The tree-based approach uses a Gibbs sampler to iteratively sample from a full
      conditional distribution, which is obtained from the classification and
      regression tree (CART) algorithm. We employ a standard multiple imputation
      procedure to account for the uncertainty of imputation. We apply the methods to
      simulated data as well as a case-control study on developmental dyslexia. Our
      results suggest that imputation generally improves efficiency over the standard
      practice of ignoring missing data. The tree-based approach performs comparably
      well as haplotype-based approaches, but the former has a computational advantage.
      The WEM approach yields the smallest bias at a price of increased variance.

PMID- 16986163
TI  - Quantifying the amount of missing information in genetic association studies.
AB  - Many genetic analyses are done with incomplete information; for example, unknown
      phase in haplotype-based association studies. Measures of the amount of available
      information can be used for efficient planning of studies and/or analyses. In
      particular, the linkage disequilibrium (LD) between two sets of markers can be
      interpreted as the amount of information one set of markers contains for testing
      allele frequency differences in the second set, and measuring LD can be viewed as
      quantifying information in a missing data problem. We introduce a framework for
      measuring the association between two sets of variables; for example, genotype
      data for two distinct groups of markers, or haplotype and genotype data for a
      given set of polymorphisms. The goal is to quantify how much information is in
      one data set, e.g. genotype data for a set of SNPs, for estimating parameters
      that are functions of frequencies in the second data set, e.g. haplotype
      frequencies, relative to the ideal case of actually observing the complete data,
      e.g. haplotypes. In the case of genotype data on two mutually exclusive sets of
      markers, the measure determines the amount of multi-locus LD, and is equal to the
      classical measure r(2), if the sets consist each of one bi-allelic marker. In
      general, the measures are interpreted as the asymptotic ratio of sample sizes
      necessary to achieve the same power in case-control testing. The focus of this
      paper is on case-control allele/haplotype tests, but the framework can be
      extended easily to other settings like regressing quantitative traits on
      allele/haplotype counts, or tests on genotypes or diplotypes. We highlight
      applications of the approach, including tools for navigating the HapMap database
      [The International HapMap Consortium, 2003], and genotyping strategies for
      positional cloning studies.

PMID- 16986164
TI  - Increasing access to clinical and educational studies.
AB  - In 2001, the National Cancer Institute (NCI) provided funds to support the
      Increasing Access to Clinical and Educational Studies (ACES) Project of the
      Thomas Jefferson University, Kimmel Cancer Center in Philadelphia. The ACES
      Project enabled the Center to engage in the systematic development of approaches
      for reducing cancer health disparities among African Americans in Philadelphia.
      This project brought together community partners, clinical partners, cancer
      prevention and control experts, and staff from an NCI-designated cancer center to
      develop and implement a community-based outreach education program, a special
      populations investigator (SPI) training program, and SPI pilot studies in cancer
      screening and clinical trials participation. At the end of 5 years, the ACES
      Project had 1) organized a steering committee, expert panel, and a network of
      community collaborators and clinical partners; 2) implemented a clinical trials
      education program for community-based nurses, lay health advocates active in
      community organizations, and health ministries in community churches; 3) mentored
      4 SPIs in cancer prevention and control research; 4) completed SPI pilot studies;
      and 5) leveraged these activities to gain support for cancer health disparities
      related research. The Project established a successful dialogue between an NCI
      designated cancer center and the African American population related to cancer
      research, and enabled SPIs from the community to adapt evidence-informed
      interventions for application in cancer prevention and control research. Lessons
      learned from the Project can guide the implementation of such projects in the
      future. Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16986165
TI  - Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated
      conditions.
AB  - We previously reported that a soluble form of the TNF-family receptor death
      receptor-3 (DR3) is expressed in osteoblasts. DR3 regulates death or
      differentiation in other tissues, and DR3 ligands occur in bone, but the function
      of DR3 in the osteoblast was unknown. We studied the expression of DR3 and the
      effects crosslinking antibodies to DR3 or of natural DR3 ligands in human
      osteoblasts. Western analysis showed that nontransformed osteoblasts and the MG63
      osteosarcoma cell line produce both soluble decoy receptor and transmembrane
      isoforms of DR3. Cell surface labeling showed that low and high DR3-expressing
      osteoblast populations occur. Verification of by cloning showed a point mutation
      in DR3 from MG63 cells. Activation of DR3 by antibody crosslinking or with DR3
      ligands caused apoptosis in osteoblasts and in MG63 cells, but only in low
      density cell cultures. In dense cultures apoptosis did not occur, but nuclear
      factor-kappaB nuclear translocation was observed under some conditions.
      Crosslinking of DR3 in high-density MG63 cultures blocked expression of bone
      matrix elements. DR3 activation in high-density nontransformed osteoblasts had
      only minor effects on cell maturation. We conclude that DR3 activation can
      mediate apoptosis in osteoblasts. Its activity is, however, highly restricted by
      its soluble ligand-binding isoform and possibly also by alternate survival
      signals. In the presence of survival signals, DR3 may affect cell maturation
      although effects on differentiation were clearly seen only in the MG63
      transformed cell line.

PMID- 16986166
TI  - BNP-induced activation of cGMP in human cardiac fibroblasts: interactions with
      fibronectin and natriuretic peptide receptors.
AB  - Cardiac remodeling involves the accumulation of extracellular matrix (ECM)
      proteins including fibronectin (FN). FN contains RGD motifs that bind integrins
      at DDX sequences allowing signaling from the ECM to the nucleus. We noted that
      the natriuretic peptide receptor A (NPR-A) sequence contains both RGD and DDX
      sequences. The goal of the current investigation was to determine potential
      interactions between FN and NPR-A on BNP induction of cGMP in cultured human
      cardiac fibroblasts (CFs). Further, we sought to determine whether a Mayo
      designed NPR-A specific RGD peptide could modify this interaction. Here we
      reconfirm the presence of all three natriuretic peptide receptors (NPR) in CFs.
      CFs plated on FN demonstrated a pronounced increase in cGMP production to BNP
      compared to non-coated plates. This production was also enhanced by the NPR-A
      specific RGD peptide, which further augmented FN associated cGMP production.
      Addition of HS-142-1, a NPR-A/B antagonist, abrogated the responses of BNP to
      both FN and the NPR-A specific RGD peptide. Finally, we defined a possible role
      for the NPR-C through non-cGMP mechanisms in mediating the anti-proliferative
      actions of BNP in CFs where the NPR-C antagonist cANF 4-28 but not HS-142-1
      blocked BNP-mediated inhibition of proliferation of CFs. We conclude that NPR-A
      interacts with components of the ECM such as FN to enhance BNP activation of cGMP
      and that a small NPR-A specific RGD peptide augments this action of BNP with
      possible therapeutic implications. Lastly, the NPR-C may also have a role in
      mediating anti-proliferative actions of BNP in CFs.

PMID- 16986167
TI  - Comparison of carbon monoxide (CO) single breath pulmonary diffusing capacity
      with non-rebreathing, open-circuit CO pulmonary diffusing capacity in healthy
      children.
AB  - INTRODUCTION: The standard technique for assessing pulmonary diffusing capacity
      of the lungs (DL) for carbon monoxide (CO) is the single breath (SB) technique.
      SB_DLco in children can be problematic because it requires a vital capacity >1.5
      L. We have developed an open-circuit technique (OC), which uses the wash-in of CO
      over a series of 8-10 normal breaths that does not require rebreathing. In this
      study, we compared the SB_DLco against the OC_DLco. METHODS: Nineteen healthy
      children between 7 and 18 years performed SB_DLco and OC_DLco tests. The mean
      SB_DLco was significantly larger than the mean OC_DLco. The mean difference
      OC_DLco minus SB_ DLco was: -2.92 +/- 4.21 ml/min/mm Hg, though the difference
      was negatively correlated with the mean of the two (r = 0.73). The lower mean
      OC_DLco was in part due to lower lung volume (as measured by alveolar volume
      (VA)) during the maneuver. In both groups there was a positive correlation
      between VA and DLco, and the mean VA was -2.17 +/- 1.07 L lower using OC compared
      to SB. The difference was again negatively correlated with the mean (r = 0.82).
      The mean OC minus SB difference in DLco/VA was: 6.06 +/- 1.98 ml/min/mm Hg/L,
      though this difference was positively correlated with the mean, r = 0.76.
      CONCLUSIONS: We found a good correlation between both techniques for DLco, VA,
      and DLco/VA. The OC offers the advantage of minimal subject cooperation, and may
      be preferable to use in children.

PMID- 16986168
TI  - Crosslinked enzyme aggregates in hierarchically-ordered mesoporous silica: a
      simple and effective method for enzyme stabilization.
AB  - alpha-chymotrypsin (CT) and lipase (LP) were immobilized in hierarchically
      ordered mesocellular mesoporous silica (HMMS) in a simple but effective way for
      the enzyme stabilization, which was achieved by the enzyme adsorption followed by
      glutaraldehyde (GA) crosslinking. This resulted in the formation of nanometer
      scale crosslinked enzyme aggregates (CLEAs) entrapped in the mesocellular pores
      of HMMS (37 nm), which did not leach out of HMMS through narrow mesoporous
      channels (13 nm). CLEA of alpha-chymotrypsin (CLEA-CT) in HMMS showed a high
      enzyme loading capacity and significantly increased enzyme stability. No activity
      decrease of CLEA-CT was observed for 2 weeks under even rigorously shaking
      condition, while adsorbed CT in HMMS and free CT showed a rapid inactivation due
      to the enzyme leaching and presumably autolysis, respectively. With the CLEA-CT
      in HMMS, however, there was no tryptic digestion observed suggesting that the
      CLEA-CT is not susceptible to autolysis. Moreover, CLEA of lipase (CLEA-LP) in
      HMMS retained 30% specific activity of free lipase with greatly enhanced
      stability. This work demonstrates that HMMS can be efficiently employed as host
      materials for enzyme immobilization leading to highly enhanced stability of the
      immobilized enzymes with high enzyme loading and activity.

PMID- 16986169
TI  - Cartilaginous tissue formation from bone marrow cells using rotating wall vessel
      (RWV) bioreactor.
AB  - This is the first successful report of the rapid regeneration of three
      dimensional large and homogeneous cartilaginous tissue from rabbit bone marrow
      cells without a scaffold using a rotating wall vessel (RWV) bioreactor, which
      simulates a microgravity environment for cells. Bone marrow cells cultured for 3
      weeks in DMEM were resuspended and cultured for 4 weeks in the chondrogenic
      medium within the vessel. Large cylindrical cartilaginous tissue with dimensions
      of (1.25 +/- 0.06) x (0.60 +/- 0.08) cm (height x diameter) formed. Their
      cartilage marker expression was confirmed by mRNA expressions of aggrecan,
      collagen type I and II, and glycosaminoglycan (GAG)/DNA ratio. Their
      cartilaginous properties were demonstrated by toluidine blue, safranin-O
      staining, and polarization.

PMID- 16986170
TI  - Effect of cerebrocrast, a new long-acting compound on blood glucose and insulin
      levels in rats when administered before and after STZ-induced diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is
      characterized by selective destruction of insulin secreting pancreatic islets
      beta-cells. The formation of cytokines (IL-1beta, IL-6, TNF-alpha, etc.) leads to
      extensive morphological damage of beta-cells, DNA fragmentation, decrease of
      glucose oxidation, impaired glucose-insulin secretion and decreased insulin
      action and proinsulin biosynthesis. We examined the protective effect of a 1,4
      dihydropyridine (DHP) derivative cerebrocrast (synthesized in the Latvian
      Institute of Organic Synthesis) on pancreatic beta-cells in rats possessing
      diabetes induced with the autoimmunogenic compound streptozotocin (STZ).
      Cerebrocrast administration at doses of 0.05 and 0.5 mg/kg body weight (p.o.) 1 h
      or 3 days prior to STZ as well as at 24 and 48 h after STZ administration
      partially prevented pancreatic beta-cells from the toxic effects of STZ, and
      delayed the development of hyperglycaemia. Administration of cerebrocrast
      starting 48 h after STZ-induced diabetes in rats for 3 consecutive days at doses
      of 0.05 and 0.5 mg/kg body weight (p.o.) significantly decreased blood glucose
      level, and the effect remained 10 days after the last administration. Moreover,
      in these rats, cerebrocrast evoked an increase of serum immunoreactive insulin
      (IRI) level during 7 diabetic days as compared to both the control normal rats
      and the STZ-induced diabetic control rats. The STZ-induced diabetic rats that
      received cerebrocrast had a significantly high serum IRI level from the 14th to
      21st diabetic days in comparison with the STZ-induced diabetic control. The IRI
      level in serum as well as the glucose disposal rate were significantly increased
      after stimulation of pancreatic beta-cells with glucose in normal rats that
      received cerebrocrast, administered 60 min before glucose. Glucose disposal rate
      in STZ-induced diabetic rats as a result of cerebrocrast administration was also
      increased in comparison with STZ-diabetic control rats. Administration of
      cerebrocrast in combination with insulin intensified the effect of insulin. The
      hypoglycaemic effect of cerebrocrast primarily can be explained by its
      immunomodulative properties. Moreover, cerebrocrast can act through
      extrapancreatic mechanisms that favour the expression of glucose transporters, de
      novo insulin receptors formation in several cell membranes as well as glucose
      uptake.

PMID- 16986171
TI  - Screening antimicrobial activity of various extracts of Artemisia dracunculus L.
AB  - The antimicrobial activities of chloroform, acetone and two different
      concentrations of methanol extracts of Artemisia dracunculus L. were studied.
      These extracts were tested against nine bacteria and four yeasts strains by the
      disc diffusion method. The results indicated that the methanol extract of A.
      dracunculus is more effective against tested microorganisms than chloroform or
      acetone extracts. The chloroform and acetone extracts were inhibitory only
      towards Pseudomonas aeruginosa (ATCC 27853). While the methanol extract that was
      diluted with 10 ml distilled water showed inhibition zones against Shigella
      (RSHI), Listeria monocytogenes ATCC 7644, P. aeruginosa (ATCC 27853), the
      methanol extract that was diluted with 5 ml distilled water showed inhibition
      zones against two different strains of Escherichia coli (RSHI, ATCC 25922),
      Shigella (RSHI), L. monocytogenes (ATCC 7644), and P. aeruginosa ATCC 27853. The
      cells of microorganisms treated with plant extracts and normal microorganism
      cells were observed by scanning electron microscope. It was apparent that cells
      are damaged after treatment with A. dracunculus.

PMID- 16986172
TI  - Perceived helpfulness and impact of social support provided by family, friends,
      and health care providers to women newly diagnosed with breast cancer.
AB  - We evaluated the helpfulness of informational, emotional, and decision-making
      support received by women newly diagnosed with breast cancer from their family,
      friends, and health care providers. Data were collected at two time points via
      patient surveys: baseline on an average 2 months post-diagnosis and follow-up at
      5 months post-baseline. In the period closer to diagnosis, majority of the women
      received helpful informational support from health care providers (84.0%);
      helpful emotional support from family (85%), friends (80.4%), and providers
      (67.1%); and helpful decision-making support from providers (75.2%) and family
      (71.0%). Emotional support at baseline and emotional and informational support at
      5-month follow-up were significantly associated with patients' health-related
      quality of life and self-efficacy outcomes (p<0.01). Perceived helpfulness of
      informational, emotional, and decision-making support provided by family,
      friends, and providers however significantly decreased over time (p<0.001).
      Cancer patients' desire significant amount of support throughout their cancer
      journey. Our results show that while patients receive a lot of support during the
      period closer to diagnosis, receipt of helpful support drops significantly within
      the first year itself. In order to facilitate cancer patients' adjustment to
      their illness, efforts need to be made to understand and address their support
      needs throughout the cancer experience.

PMID- 16986173
TI  - Psychosocial registry for persons with cancer: a method of facilitating quality
      of life and symptom research.
AB  - Research focused on the psychosocial aspects of the experience of persons with
      cancer and their family caregivers is hampered by the methodological challenges
      inherent in quality of life research. A data registry offers a potential solution
      to many of these problems in providing a large, comprehensive database, using
      standardized instruments. We report here our preliminary experience with
      establishing a Psychosocial Registry designed to advance research in the
      psychological, social, and spiritual aspects of quality of life of newly
      diagnosed cancer patients and their family caregivers. The first six months of
      enrollment demonstrated that the majority of newly diagnosed patients approached
      for consent (68%) and their primary family caregiver (92%) were willing to
      participate in the registry; of these, 80% also agreed to be contacted in the
      future for additional studies. Face-to-face interview was the preferred method of
      data collection. Our preliminary experience suggests that continuation of the
      registry with the current modest level of resources would generate a sample of
      approximately 1000 patients in three years. The long-range goal is to establish a
      national psychosocial data registry that will enroll patients at diagnosis and
      follow them through the entire cancer experience, including end of life or
      survivorship.

PMID- 16986174
TI  - Critical evaluation of elective termination of pregnancy in a tertiary fetal
      medicine center during 43 months: correlation of prenatal diagnosis findings and
      postmortem examination.
AB  - OBJECTIVES: The aim of this study is the critical evaluation of cases of elective
      termination of pregnancy (TOP) in the Prenatal Diagnosis Center of S. Joao
      Hospital. MATERIAL AND METHODS: We performed a retrospective study of cases of
      elective TOP over a 43-month period in a tertiary referral hospital. The fetal
      indications for termination were analyzed. A comparative study of the prenatal
      diagnosis, established by ultrasound, and the results of postmortem findings, was
      performed. These were classified as having complete agreement, complete
      disagreement and major agreement with additional information. RESULTS: In total,
      during this period, 76 elective terminations of pregnancy were performed due to
      fetal causes. The number of fetal identified grounds was 25 cases of chromosomal
      abnormalities, 36 cases of morphological anomalies and 15 cases of other fetal
      situations. The comparison between ultrasound and fetopathologic findings showed
      complete agreement of diagnosis in 61.1% of cases, and no case of absolute
      discordance was identified. Major concordance with additional information was
      found in 38.9% of cases, with an increased risk of recurrence in six cases, and a
      decreased estimated risk of recurrence in three cases. DISCUSSION: This study
      reinforces the importance of the systematic evaluation of all cases of elective
      TOP by autopsy performed by a specialist fetal pathologist. This is the most
      reliable way of assessing the adequacy of prenatal diagnosis and implementing
      quality control. More than corroborating or correcting the prenatal diagnosis,
      systematic autopsy may establish a definite diagnosis, adjust prognosis and may
      be helpful in counseling the parents for a future pregnancy.

PMID- 16986175
TI  - Successful preimplantation genetic diagnosis for alpha- and beta-thalassemia in
      China.
AB  - METHODS & RESULTS: In southern China, the average carrier rates of alpha
      thalassemia and beta-thalassemia in the population are as high as 10.3% and 2.8%,
      respectively. Because of the high rates, they are known as 'social diseases' in
      some regions. In this study, the fluorescent gap PCR, which can detect the alpha
      thalassemia Southeast Asia deletion (SEA deletion), was applied in four clinical
      applications of preimplantation genetic diagnosis (PGD) on four couples, among
      whom both partners were alpha-thalassemia carriers. Two patients became pregnant
      and two healthy babies were born, which confirmed the PGD results. The single
      cell multiplex nested PCR followed by reverse dot blot (RDB), which can
      simultaneously detect the 16 beta-thalassemia mutations in the Chinese
      population, was applied in four clinical PGD cycles on four couples among whom
      both partners were beta-thalassemia carriers. One pregnancy was achieved and it
      resulted in a live healthy birth, which confirmed the results of PGD. The
      amplification efficiencies of the two protocols described above were 89.5% and
      93.9%, respectively. The allele drop-out (ADO) rates of these two protocols were
      5.9% and 10.9%, respectively. CONCLUSION: These studies represent the successful
      applications of PGD protocols that can detect more than 95% of alpha- and beta 
      thalassemia mutations in the Chinese population.

PMID- 16986176
TI  - Seeking informed consent to cancer clinical trials; evaluating the efficacy of
      doctor communication skills training.
AB  - INTRODUCTION: Clinical trials have come to be regarded as the gold standard for
      treatment evaluation. However, many doctors and their patients experience
      difficulties when discussing trial participation, leading to poor accrual to
      trials and questionable quality of informed consent. We have previously developed
      a communication skills training program based on a typology for ethical
      communication about Phase II and III clinical trials within four categories. The
      training program consisted of a 1 day experiential workshop that included
      didactic teaching, exemplary video and role play. The aim of this study was to
      evaluate the effectiveness of the communication skills training workshop. METHOD:
      Oncologists were recruited from three major teaching hospitals conducting
      oncology outpatient clinics in three Australian capital cities. Ten oncologists
      and 90 of their adult cancer patients who were eligible for a Phase II or III
      clinical trial participated. Ninety informed consent consultations were
      audiotaped before (n = 59) and after (n = 31) training, and fully transcribed.
      The presence or absence of each domain component was coded and these were summed
      within categories. A coding manual was produced which enabled standardization of
      the coding procedure. Patients completed questionnaires before and after the
      consultation, and doctors completed a short measure of satisfaction after the
      consultation. RESULTS: Doctors increased their use of some aspects of shared
      decision-making behavior (t(87) = -1.945, p = 0.05) and described some aspects of
      essential ethical/clinical information more commonly. In addition they used less
      coercive behaviors (z = -1.976, p = 0.048). However, they did not provide more
      clinical information or structure their consultations in the recommended fashion.
      Patients in the post-training cohort reported more positive attitudes to clinical
      trials, but other outcomes were not affected by the intervention. CONCLUSIONS:
      This short training programme demonstrated limited success in improving the
      oncologist's communication skills when gaining informed consent. A larger
      randomized controlled trial of extended training is now underway.

PMID- 16986177
TI  - Supramolecular assemblies of sulfonatocalixarenes with phenanthroline: factors
      governing capsule formation versus bilayer arrangements.
AB  - Four crystalline complexes were prepared by the inclusion complexation of the
      1,10-phenanthrolinium ion (Phen) with p-sulfonatothiacalix[4]arene (TCAS) (2 from
      a solution at pH 1-2 and 4 from 1 M HCl) and with p-sulfonatocalix[5]arene (C5AS)
      (3 from a solution at pH 1-2 and 5 from 1 M HCl) upon varying the acidity of the
      solution. By combining the results obtained for complexes 2-5 with those for our
      previously reported complex (1), p-sulfonatocalix[4]arene (C4AS) complexed to
      Phen, it was revealed that p-sulfonatocalixarenes (CASs) form "bis-molecular"
      capsules (1, 2, and 3) around Phen at pH 1-2, whereas complexes 4 and 5 display
      distinct host-guest inclusion behavior at higher acid concentrations. The degree
      of compactness of the capsules increases with the enlargement of the calixarene
      cavity, which is affected significantly by both the penetration depth of Phen and
      the structure of the Phen dimer. Furthermore, the complexation behavior of
      TCAS/C5AS with Phen in 1 M DCl was investigated by using NMR spectroscopy, and
      was discussed in comparison with the previously reported results obtained from
      solutions at pH 2.0.

PMID- 16986178
TI  - A highly active and selective nanocomposite catalyst for C7+ paraffin
      isomerization.

PMID- 16986179
TI  - A C3-symmetric palladium catalyst with a phosphorus-based tripodal ligand.

PMID- 16986180
TI  - Gold(I)-catalyzed reaction of 1-(1-alkynyl)-cyclopropyl ketones with
      nucleophiles: a modular entry to highly substituted furans.

PMID- 16986181
TI  - Proton magnetic shielding tensors in benzene-from the individual molecule to the
      crystal.

PMID- 16986182
TI  - A main-group analogue of housene: the subtle influence of the inert-pair effect
      in group 15 clusters.

PMID- 16986183
TI  - Mono- and dimetalated ferrocenylcopper complexes by tin-copper exchange.

PMID- 16986184
TI  - Remarkably low catalyst loading in Bronsted acid catalyzed transfer
      hydrogenations: enantioselective reduction of benzoxazines, benzothiazines, and
      benzoxazinones.

PMID- 16986185
TI  - New methods for anion recognition and signaling using nanoscopic gatelike
      scaffoldings.

PMID- 16986186
TI  - Stereocontrolled total synthesis of bengazole a: a marine bisoxazole natural
      product displaying potent antifungal properties.

PMID- 16986187
TI  - Mechanistic questions about the reaction of molecular oxygen with palladium in
      oxidase catalysis.

PMID- 16986188
TI  - Diastereoselective gold-catalyzed cycloisomerizations of ene-ynamides.

PMID- 16986189
TI  - Cyclobutadiene: the antiaromatic paradigm?

PMID- 16986190
TI  - Low-valent silicon cations with two-coordinate silicon and aromatic character.

PMID- 16986191
TI  - A self-assembled pyrrolic cage receptor specifically recognizes beta
      glucopyranosides.

PMID- 16986192
TI  - Rationalization and prediction of solution enantiomeric excess in ternary phase
      systems.

PMID- 16986193
TI  - Characteristics of ligand recognition by a glmS self-cleaving ribozyme.

PMID- 16986194
TI  - A metal-based trisimidazolium cage that provides six C-H hydrogen-bond-donor
      fragments and includes anions.

PMID- 16986195
TI  - Isolation of cyclopropenylidene-lithium adducts: the Weiss-Yoshida reagent.

PMID- 16986196
TI  - The cell-penetrating peptide TAT(48-60) induces a non-lamellar phase in DMPC
      membranes.
AB  - Cell-penetrating peptides (CPPs) are short polycationic sequences that can
      translocate into cells without disintegrating the plasma membrane. CPPs are
      useful tools for delivering cargo, but their molecular mechanism of crossing the
      lipid bilayer remains unclear. Here we study the interaction of the HIV-derived
      CPP TAT (48-60) with model membranes by solid-state NMR spectroscopy and electron
      microscopy. The peptide induces a pronounced isotropic (31)P NMR signal in
      zwitterionic DMPC, but not in anionic DMPG bilayers. Octaarginine and to a lesser
      extent octalysine have the same effect, in contrast to other cationic amphiphilic
      membrane-active peptides. The observed non-lamellar lipid morphology is
      attributed to specific interactions of polycationic peptides with phosphocholine
      head groups, rather than to electrostatic interactions. Freeze-fracture electron
      microscopy indicates that TAT(48-60) induces the formation of rodlike, presumably
      inverted micelles in DMPC, which may represent intermediates during the
      translocation across eukaryotic membranes.

PMID- 16986197
TI  - Voltammetric sizing of a sphere.
AB  - The size of a glass sphere positioned in the center of a microdisk electrode is
      determined by using a simple electrochemical procedure and is confirmed,
      additionally, by a microscopical measurement of the sphere at the time of the
      electrochemical measurement. The cyclic voltammetric response of the naked
      electrode and of the electrode with the sphere positioned in its center is
      recorded over a wide range of scan rates (0.002-1.5 V s(-1)). The size of the
      sphere is then determined by comparison of the experimental voltammogram with
      simulations for each individual scan rate.

PMID- 16986198
TI  - Diastereodifferentiation of novel naphthalene dyads by fluorescence quenching and
      excimer formation.
AB  - Four new bichromophoric naphthalene dyads in form of diastereomeric pairs are
      synthesized and photophysically characterized. For a closely related group of
      compounds (NAP-NAP, MNAP-NAP, MNAP-MNAP), systematic variation of the urea linker
      led to the observation of intramolecular fluorescence quenching for tertiary
      urea, but not for secondary urea. Chiral information contained in the dyads has
      an impact on the efficiency of this process. Furthermore, for the case of (R,R)
      MNAP-MNAP, excimer formation in the pre-organized dyad was noted, while being
      absent in the corresponding (R,S) diastereomer. These differences in
      photophysical behavior are ascribed to the geometry of the linker and to the
      chiral information contained in the diastereomeric compounds. Other dyads, such
      as NPX-NPX, included naproxen as the chromophore. For these compounds strong
      excimer emission is obtained, however, only very small diastereodifferentiation
      is observed for the two investigated stereoisomers.

PMID- 16986199
TI  - Origin of the large spin-orbit effect in the vibrational frequencies of
      haloalkane cations.

PMID- 16986200
TI  - Synthesis of libraries of 16beta-aminopropyl estradiol derivatives for targeting
      two key steroidogenic enzymes.
AB  - Two libraries, each consisting of 48 16beta-aminopropyl estradiol derivatives,
      phenols and sulfamates, respectively, were synthesized by solid-phase parallel
      chemistry through a seven-step reaction sequence. Following the attachment of a
      C18-steroid sulfamate precursor on a trityl chloride resin, diversity elements
      were first introduced on the 16beta-aminopropyl chain of the steroid by acylation
      reactions with eight Fmoc-amino acids. After deprotection, the free amine
      function of the resulting compounds was reacted with six carboxylic acids for the
      introduction of a second diversity level. The two variants employed for the
      cleavage of compounds from the solid support, acidic and nucleophilic, allowed
      the corresponding libraries of sulfamate and phenol derivatives in yields of 8-50
      % and 13-58 % to be obtained with an average HPLC purity of 94 % and 91 %,
      respectively. Potent steroid sulfatase inhibitors and interesting SAR results
      were generated from the screening of the sulfamate library. Furthermore, moderate
      inhibitors of type 1 17beta-HSD resulted from the partial screening of phenol
      library. Thus, these two categories of compounds were synthesized to rapidly
      identify potential inhibitors of steroid biosynthesis for the hormonal therapy of
      estrogen-dependent diseases, and also to demonstrate the versatility and
      efficiency of the recently developed sulfamate linker.

PMID- 16986201
TI  - Predicting compound selectivity by self-organizing maps: cross-activities of
      metabotropic glutamate receptor antagonists.

PMID- 16986202
TI  - 2-Anilinobenzamides as SIRT inhibitors.

PMID- 16986203
TI  - Role of rotational alignment in dissociative chemisorption and oxidation: O2 on
      bare and CO-precovered Pd(100).

PMID- 16986204
TI  - Evolution of polyoxoniobate cluster anions.

PMID- 16986205
TI  - Cancer support groups: a critical review of empirical studies.
AB  - Support groups for adults affected by cancer are widely offered by local
      community and national agencies in North America. This type of psychosocial
      intervention is defined in terms of its structure and functions, and its
      theoretical underpinnings and models of practice are described. Forty-four
      empirical studies of professionally led cancer support groups are summarized and
      critically reviewed. These studies include 32 outcome evaluations of randomized
      controlled trials, two process evaluations, and 10 consumer satisfaction studies.
      The findings reveal high levels of consumer satisfaction, and the outcome
      evaluations substantiate the morale and other quality of life benefits short of
      prolonging life. Discussion centers on priorities for future research and
      practice.

PMID- 16986208
TI  - Proteome profile of the MCF7 cancer cell line: a mass spectrometric evaluation.
AB  - The development of novel proteomic technologies that will enable the discovery of
      disease specific biomarkers is essential in the clinical setting to facilitate
      early diagnosis and increase survivability rates. We are reporting a shotgun two
      dimensional (2D) strong cationic exchange/reversed-phase liquid
      chromatography/electrospray ionization tandem mass spectrometry (SCX/RPLC/ESI
      MS/MS) protocol for the analysis of proteomic constituents in cancerous cells.
      The MCF7 breast cancer cell line was chosen as a model system. A series of
      optimization steps were performed to improve the LC/MS experimental setup, sample
      preparation, data acquisition and database search protocols, and a data filtering
      strategy was developed to enable confident identification of a large number of
      proteins and potential biomarkers. This research has resulted in the
      identification of >2000 proteins using multiple filtering and p-value sorting.
      Approximately 1600-1900 proteins had p < 0.001, and, of these, approximately 60%
      were matched by >or=2 unique peptides. Alternatively, >99% of the proteins
      identified by >or=2 unique peptides had p < 0.001. When searching the data
      against a reversed database of proteins, the rate of false positive
      identifications was 0.1% at the peptide level and 0.4% at the protein level. The
      typical reproducibility in detecting overlapping proteins across replicate runs
      exceeded 90% for proteins matched by >or=2 unique peptides. According to their
      biological function, approximately 200 proteins were involved in cancer-relevant
      cellular processes, and over 25 proteins were previously described in the
      literature as putative cancer biomarkers, as they were found to be differentially
      expressed between normal and cancerous cell states. Among these, biomarkers such
      PCNA, cathepsin D, E-cadherin, 14-3-3-sigma, antigen Ki-67, TP53RK, and
      calreticulin were identified. These data were generated by subjecting to MS
      analysis approximately 42 microg of sample, analyzing 16 SCX peptide fractions,
      and interpreting approximately 55,000 MS2 spectra. Total MS time required for
      analysis was 40 h.

PMID- 16986207
TI  - Lipidomic analysis of twenty-seven prostanoids and isoprostanes by liquid
      chromatography/electrospray tandem mass spectrometry.
AB  - Prostanoids are potent mediators of many physiological and pathophysiological
      processes. Of the many analytical methodologies used for their qualitative and
      quantitative analysis, electrospray tandem mass spectrometry coupled to liquid
      chromatography (LC/ESI-MS/MS) offers a rapid, sensitive and versatile system
      applicable to lipidomic analyses. We have developed an LC/ESI-MS/MS assay for
      twenty-seven mediators including prostaglandins, prostacyclines, thromboxanes,
      dihydroprostaglandins and isoprostanes. The assay was liner over the
      concentration range 1-100 pg/microL. The limits of detection and quantitation
      were 0.5-50 and 2-100 pg, respectively, whilst recoveries were from 83-116%
      depending on the metabolite. The assay can be applied to the profiling of
      prostanoids produced by a variety of biological fluids and extracts including
      brain, liver, plasma and urine, thus facilitating our understanding of the role
      of these lipid mediators in health and disease, as well as assisting in drug
      development.

PMID- 16986209
TI  - Quantitative analyses of indoloquinazoline alkaloids in Fructus Evodiae by high
      performance liquid chromatography with atmospheric pressure chemical ionization
      tandem mass spectrometry.
AB  - Fructus Evodiae (Wuzhuyu), the fruits of Evodia rutaecarpa and related varieties,
      is widely used in traditional Chinese medicine. The bioactive constituents
      include the indoloquinazoline alkaloids rutaecarpine, evodiamine and
      dehydroevodiamine. A new assay based on high-performance liquid
      chromatography/atmospheric pressure chemical ionization tandem mass spectrometry
      (HPLC/UV/APCI-MS/MS) was developed for the measurement of the indoloquinazoline
      alkaloids in commercial Fructus Evodiae products. Initially, the MS/MS
      fragmentation pathways of indoloquinazoline alkaloids were investigated to
      identify fragment ions that might be useful for the sensitive and selective
      detection of trace indoloquinazoline alkaloids during LC/MS/MS. Then,
      quantitative MS analysis of five indoloquinazoline alkaloids in 12 commercial
      Fructus Evodiae products from different geographical sources was performed.
      Analyte recovery was in the range of 97.5-105.3% for all with relative standard
      deviations (RSDs) below 6%, the intra-assay and inter-assay RSDs were less than
      7%, and good linear relationships were shown with correlation coefficients for
      the analytes exceeding 0.999. Therefore, this LC/MS/MS assay facilitated the
      rapid quantitative analysis of rutaecarpine, evodiamine, evodiamide, 14
      formyldihydrorutaecarpine and dehydroevodiamine in 12 commercial Fructus Evodiae
      products with excellent recovery, repeatability, accuracy and sensitivity. This
      method is simple and specific and can be used for identification and quality
      control of this traditional Chinese remedy.

PMID- 16986210
TI  - Identification and quantitation of phenolic compounds in faecal matrix by
      capillary gas chromatography and nano-electrospray mass spectrometry.
AB  - Very few relevant methods have been described for the detection and quantitation
      of phenolic compounds in faecal matrix. Extraction with conventional organic
      solvents such as chloroform/methanol (2:1, Folch reagent), methanol and ethanol
      (72%) showed high extraction efficiency for lipids and also gave good recovery of
      the major phenolic compounds present in the matrix. However, in comparison with a
      newly developed phosphate buffer method, the yield of minor phenolics was
      negligible when detected by these conventional methods. Conventional methods also
      lead to contamination of the ion source of the mass spectrometer and rapid
      deterioration of column performance mostly due to the high concentration of
      lipids. However, if the faecal matrix is initially extracted with phosphate
      buffer, and the extract acidified and re-extracted with diethyl ether, the range
      and yield of phenolic compounds are enhanced and the problem of lipid
      contamination is substantially alleviated. Following pilot studies and
      optimisation of the procedure, individual phenolic compounds (n = 29) were
      identified by nano-electrospray ionisation mass spectrometry (nano-ESI-MS), nano
      ESI-tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry
      (GC/EI-MS) and quantitated (n = 27) by GC/MS in subsets (n = 5) of faecal
      samples, collected during the European Agency for Cancer Prevention calcium/fibre
      intervention study from four European countries (Italy, Germany, Spain and
      Denmark). A range of phenolic compounds (mainly acids) was detected, dominated by
      phenylacetic, benzoic, phenylpropionic and m-hydroxyphenylpropionic acids,
      representing on average 9.91 (93%), 8.25 (92%), 9.45 (95%) and 11.05 (98%) mM in
      the Italian, German, Spanish and Danish samples, respectively. The new method
      should enable large epidemiologic, case-control and intervention studies on the
      relevance of phenolic antioxidants in the aetiology of colorectal cancer to be
      conducted in the future.

PMID- 16986211
TI  - Highly efficient enrichment and subsequent digestion of proteins in the
      mesoporous molecular sieve silicate SBA-15 for matrix-assisted laser
      desorption/ionization mass spectrometry with time-of-flight/time-of-flight
      analyzer peptide mapping.
AB  - Based on a previous study of protein digestion inside the nanoreactor channels of
      the mesoporous molecular sieve silicate SBA-15 (Chem. Eur. J. 2005, 11: 5391), we
      have developed a highly efficient enrichment and subsequent tryptic digestion of
      proteins in SBA-15 for matrix-assisted laser desorption/ionization mass
      spectrometry with time-of-flight/time-of-flight analyzer (MALDI-TOF/TOF) peptide
      mapping. The performance of the method is exemplified with myoglobin and
      cytochrome c. First, protein adsorption isotherms for two standard proteins with
      a range of initial concentration of proteins were investigated at room
      temperature. The results revealed that the kinetic adsorption rate of a protein
      within SBA-15 was independent of initial protein concentration, and a 15-min
      protein enrichment within SBA-15 could be enough for protein identification in
      biological samples. It was noticed that no washing steps were needed to avoid
      protein loss due to desorption from the mesochannels into solution. Second,
      protein digestion inside the channels of SBA-15 was also optimized. After
      adsorption of proteins into SBA-15 in 15 min, the trypsin solution (pH 8) was
      directly added to the SBA-15 beads with immobilized proteins by centrifugation,
      and then the digestion was performed for 15 min at 37 degrees C. It was observed
      that a higher peptide sequence covering of 98% for myoglobin was obtained by
      MALDI-TOF/TOF analysis, compared to in-solution digestion. So the protein
      digestion inside SBA-15 was proved to be significantly faster and yielded a
      better sequence coverage. The new procedure allows for rapid protein enrichment
      and digestion inside SBA-15, and has great potential for protein analysis.

PMID- 16986212
TI  - Ionization energies of LinX (n = 2, 3; X = Cl, Br, I) molecules.
AB  - Molecules of Li(n)X (n = 2, 3; X = Cl, Br, I) were examined with a magnetic
      sector mass spectrometer by surface ionization using a triple rhenium filament
      impregnated with fullerene (C60). The ionization energies obtained for Li(2)Cl,
      Li(2)Br and Li(2)I molecules are 3.8 +/- 0.1, 3.9 +/- 0.1 and 4.0 +/- 0.1 eV,
      respectively. The first ionization energy of Li(2)Cl is documented, while there
      are no literature data for the ionization energies of Li(2)Br and Li(2)I. The
      molecules of Li(3)Cl, Li(3)Br and Li(3)I were detected experimentally for the
      first time with ionization energies of 4.0 +/- 0.1, 4.1 +/- 0.1 and 4.1 +/- 0.1
      eV, respectively. The ionization energies of Li(n)X (n = 2, 3; X = Cl, Br, I) are
      in correlation with the theoretical prediction of their hyperlithiated
      configurations.

PMID- 16986214
TI  - Gone, gone and going.
AB  - Biomedicine swallows the lion's share of life science funding but there is
      mounting concern that the health of ecosystems should be demanding more
      attention. Nigel Williams reports.

PMID- 16986215
TI  - Abstracts of the 190th Meeting of the Pathological Society of Great Britain and
      Ireland, 4-7 July 2006.

PMID- 16986216
TI  - Abstracts of the 22nd International Conference on Pharmacoepidemiology and
      Therapeutic Risk Management, Lisbon, Portugal, 24-27 August 2006.

PMID- 16986217
TI  - Professor Georges A. Guiochon's 75th birthday.

PMID- 16986218
TI  - World Heart Day.

PMID- 16986219
TI  - Monocular transparency and unpaired stereopsis.
AB  - Howard and Duke [Howard, I. P. & Duke, P. A. (2003). Monocular transparency
      generates quantitative depth. Vision Research, 43, 2615-2621] recently proposed a
      new source of binocular information they claim is used to recover depth in
      stereoscopic displays. They argued that these displays lack conventional
      disparity and that the metrical depth experienced results from transparency
      rather than occlusion relations. Using a variety of modified versions of their
      stimuli, we show here that the conditions for transparency are not required to
      elicit the depth experienced in their stereograms. We demonstrate that
      quantitative and precise depth depended not on the presence of transparency but
      horizontal contours of the same contrast polarity. Depth was attenuated,
      particularly at larger target offsets, when horizontal contours had opposite
      contrast polarity for at least a portion of their length. We also show that a
      demonstration they used to control for the role of horizontal contours can be
      understood with previously identified mechanisms involved in the computations
      associated with stereoscopic occlusion. These results imply that the findings
      reported by Howard and Duke can be understood with mechanisms responsible for the
      computation of binocular disparity and stereoscopic occlusion.

PMID- 16986220
TI  - Escape from fatal fusion.
AB  - In 1971, a seminal paper from the laboratory of Philip D'Arcy Hart reported that
      the intracellular pathogen Mycobacterium tuberculosis avoids destruction in the
      cell's lysosomes by avoiding these organelles altogether-a trick now known to be
      used by many other intracellular pathogens.

PMID- 16986221
TI  - Children and adolescents' capacity to provide informed consent for participation
      in research.
AB  - Researchers who work with children and adolescents are confronted with a special
      set of ethical issues regarding informed consent. Federal guidelines generally
      stipulate that minors cannot provide informed consent for participation in
      research. Instead parental or guardian permission must be obtained for a minor to
      participate in research. However the literature in developmental psychology has
      shown that adolescents are able to make meaningful decisions and advocates for
      youth have argued that researchers must respect the autonomy rights of children
      and adolescents. The present review examines the developmental literature on
      children and adolescents' capacities to make informed, voluntary, and rational
      decisions to participate in research. The purposes and benefits of assent are
      identified. Recommendations are offered on how to enhance and respect minors'
      developing autonomy while protecting them from risks of research.

PMID- 16986222
TI  - Improving early detection of breast and cervical cancer in Chinese and Vietnamese
      immigrant women.

PMID- 16986223
TI  - Chronic graft-versus-host disease.

PMID- 16986224
TI  - Alternatives for protecting privacy while respecting patient care and public
      health needs.
AB  - This paper begins with a discussion of the value of privacy, especially for
      medical records in an age of advancing technology. I then examine three
      alternative approaches to protection of medical records: reliance on governmental
      guidelines, the use of corporate self-regulation, and my own third hybrid view on
      how to maintain a presumption in favor of privacy with respect to medical
      information, safeguarding privacy as vigorously and comprehensively as possible,
      without sacrificing the benefits of new information technology in medicine. None
      of the three models I examine are unproblematic, yet it is crucial to weigh the
      strengths and weaknesses of these alternative approaches.

PMID- 16986225
TI  - Using genetic information while protecting the privacy of the soul.
AB  - Computing plays an important role in genetics (and vice versa). Theoretically,
      computing provides a conceptual model for the function and malfunction of our
      genetic machinery. Practically, contemporary computers and robots equipped with
      advanced algorithms make the revelation of the complete human genome imminent-
      computers are about to reveal our genetic souls for the first time. Ethically,
      computers help protect privacy by restricting access in sophisticated ways to
      genetic information. But the inexorable fact that computers will increasingly
      collect, analyze, and disseminate abundant amounts of genetic information made
      available through the genetic revolution, not to mention that inexpensive
      computing devices will make genetic information gathering easier, underscores the
      need for strong and immediate privacy legislation.

PMID- 16986227
TI  - Liquid chromatography problem solving and troubleshooting. HPLC-time-of-flight
      (TOF) mass spectrometer.

PMID- 16986226
TI  - Community-acquired MRSA among HIV-infected patients rapidly rising.

PMID- 16986228
TI  - Targeting hypertension with valsartan: Lessons learned from the Valsartan/HCTZ
      versus Amlodipine in stage II hypertensive patients (VASt) trial.
AB  - Many patients with hypertension, especially those at increased risk because of
      additional cardiovascular risk factors, require treatment with more than one
      antihypertensive agent to achieve target blood pressure (BP) goals. Many
      different classes of antihypertensive agents are available: a renin-angiotensin
      aldosterone system (RAAS) blocker and a diuretic are widely used in combination.
      Here we report the results of the recently completed Valsartan/HCTZ versus
      Amlodipine in STage II hypertensive patients (VAST) trial. In this 24-week study,
      patients with moderate hypertension and at least one other cardiovascular risk
      factor were treated with a combination of valsartan 160 mg and
      hydrochlorothiazide (HCTZ) 12.5 or 25 mg once daily (o.d.), or with amlodipine
      monotherapy (10 mg o.d.). Overall, valsartan plus HCTZ 25 mg reduced systolic BP
      significantly more than amlodipine monotherapy, and with fewer adverse events. In
      addition, combination therapy resulted in a trend towards more favourable
      outcomes with respect to pro-thrombotic and proinflammatory markers than
      amlodipine alone.

PMID- 16986229
TI  - Letter to the Editorial Board of Biochemistry (Moscow).

PMID- 16986230
TI  - Angiotensin receptor blockers: Cardiovascular protection in the metabolic
      syndrome.
AB  - It is well recognised that the metabolic syndrome, a constellation of risk
      factors including obesity, hypertension, insulin resistance and dyslipidaemia, is
      associated with an increased risk of cardiovascular complications and the
      development of Type 2 diabetes. Consequently, timely identification and
      management of all components of the metabolic syndrome is warranted. In
      particular, guidelines have emphasised the importance of targeting elevated blood
      pressure (BP) and dyslipidaemia as a method of reducing global cardiovascular
      risk. Findings from the Valsartan Antihypertensive Long-term Use Evaluation
      (VALUE) trial show that the angiotensin receptor blocker, valsartan, reduces
      cardiovascular events and the development of Type 2 diabetes in high-risk
      individuals. This profile is being further explored in the ongoing Nateglinide
      And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.
      Given the potential advantages to patients and physicians of tackling more than
      one of the components of the metabolic syndrome, antihypertensive agents such as
      valsartan would appear to be and important addition to the management of
      vulnerable patients at high risk of cardiovascular events.

PMID- 16986231
TI  - Use of valsartan in post-myocardial infarction and heart failure patients.
AB  - Left ventricular (LV) dysfunction and/or heart failure (HF) are frequent
      complications of hypertension and myocardial infarction (MI), placing affected
      patients at increased risk of significant morbidity and premature death. Given
      that the renin-angiotensin-aldosterone system (RAAS) is activated and of
      pathophysiological importance in such patients, a strong therapeutic rationale
      exists to target the main effector mechanism (that is, angiotensin II [Ang II])
      in order to lessen the associated morbidity and mortality burden. Angiotensin
      converting enzyme (ACE) inhibitors have been shown to reduce mortality and LV
      dysfunction and to slow disease progression in patients with HF, including high
      risk, post-MI patients. However, ACE inhibitors (ACE-Is) may not provide optimal
      long-term RAAS blockade (a finding that is associated with a worse prognosis) and
      many patients are unable to tolerate such therapy (because of troublesome dry
      cough, for example). In contrast, Ang II receptor blockers (ARBs) may block the
      RAAS more completely than ACE-Is and appear to be better tolerated. Several large
      scale trials gave evaluated the efficacy of ARBs in patients with LV dysfunction
      and/or HF (including high-risk, post-MI patients), and have confirmed their
      utility as an efficacious and well-tolerated alternative to ACE-Is in this
      setting.

PMID- 16986232
TI  - If cancer is a special case of phenoptosis, how can we conquer it?

PMID- 16986233
TI  - Position of the American Dietetic Association: child and adolescent food and
      nutrition programs.
AB  - It is the position of the American Dietetic Association that all children and
      adolescents, regardless of age, sex, socioeconomic status, racial diversity,
      ethnic diversity, linguistic diversity, or health status, should have access to
      food and nutrition programs that ensure the availability of a safe and adequate
      food supply that promotes optimal physical, cognitive, social, and emotional
      growth and development. Appropriate food and nutrition programs include food
      assistance and meal programs, nutrition education initiatives, and nutrition
      screening and assessment followed by appropriate nutrition intervention and
      anticipatory guidance to promote optimal nutrition status. Food and nutrition
      programs create a safety net that ensures that children and adolescents at risk
      for poor nutritional intakes have access to a safe, adequate, and nutritious food
      supply and nutrition screening, assessment, and intervention. It is important
      that continued funding be provided for these programs, which consistently have
      been shown to have a positive impact on child and adolescent health and well
      being. Food and nutrition programs serve as a means to prevent or reduce hunger
      and food insecurity, but also as a vehicle for nutrition education and promotion
      of physical activity designed to prevent or reduce overweight and prevent chronic
      disease. It is the role of the registered dietitian to support adequate and
      sustained funding for food and nutrition programs, universal health care
      reimbursement for nutrition services, and the use of research and surveillance
      programs to evaluate and improve these programs. In addition, the registered
      dietitian and dietetic technician, registered, are responsible for serving as a
      nutrition resource to all groups and individuals providing services to children
      and adolescents, acting as an advocate for the establishment of child-care,
      school, and community settings conducive to the development of good nutrition
      habits.

PMID- 16986235
TI  - Managing the storm.

PMID- 16986236
TI  - [Fernando Ulloa: interview by Gustavo Lipovetzky and Martin Agrest].

PMID- 16986237
TI  - [Psychiatrists and psychotherapists: a peaceful coexistence?].
AB  - Particular issues concerning the meeting between psychiatrists and
      psychotherapists in patients' treatments are developed. Standing conceptions of
      mental illness, its etiopathogeny, the place of each therapist, and split
      transferences induced by combined treatment are discussed.

PMID- 16986238
TI  - [Problems in therapeutic management at a psychoanalysis hospital. Classical
      article. 1947].

PMID- 16986240
TI  - [Structured summary].

PMID- 16986239
TI  - [On psychiatric institutionalization].

PMID- 16986241
TI  - [The Public Health system and worker's health].

PMID- 16986242
TI  - [The efficiency of natural fertility control: new perspectives].

PMID- 16986243
TI  - [The influence of various dietetic and hygienic changes on the epidemiology of
      infantile gastro-enteritis].
AB  - The high incidence of infantile gastro-enteritis in the "Arturo Eryies" Health
      Area, the infrequent identification of the casual agent, and the heavy costs
      incurred (greater than 2 million pesetas per year) were the factors which led to
      the establishment of an action plan intended to reduce the incidence of the
      disease, gain a better understanding of the causal agents involved and to reduce
      the level of hospital admittance and the ensuing costs. The first year's activity
      involved an individualised information campaing about preventive and therapeutic
      measures, modifications to the feeding programme during the first year, and
      systematic biological studies: although the frequency of gastroenteritis was
      reduced from 19.5 % to 16.6 %, and identification of the causal agent was
      increased from 8.9 % to 21.2 %, the level of hospitalisation did not
      significantly decrease (from 4 % to 3.2 %). Individualised health education
      concentrating on rules of hygiene for the preparation and conservation of food
      and preventive dietetic measure to be taken when the symptoms appeared, together
      with systematic biological study does reduce the incidence of infantile
      gastroenteritis and thus the cost, while also providing better epidemiological
      information.

PMID- 16986244
TI  - [Evaluation of the chronic airflow obstruction programme].
AB  - The article evaluates the chronic airflow obstruction programme operating in the
      Family and Community Medicine Teaching Unit of Segovia since the end of 1987. The
      evaluation period covers from October 1989 to October 1990. The results are
      compared with those obtained from the first evaluation made and with the
      objectives of the programme. The total of cases and population at risk was 111,
      41.1% of the target; this low success rate was due to a reduction in the capture
      of new cases and to a loss of 28.8% of patients from the programme. We obtained a
      higher number of patients showing clinical improvement and managed to persuade
      15% of those at risk to stop smoking. Nevertheless we did not, in general terms,
      achieve an improvement in the quality of attendance relative to the objectives
      established for the programme nor relative to the first evaluation period.

PMID- 16986245
TI  - [Hearing damage caused by workplace noise among patients given audiometry tests
      in general practice].
AB  - OBJECTIVE: The objective of the present study was to identify the prevalence of
      hearing damage caused by workplace noise among patients presenting hearing loss
      and among those given audiometry tests at primary health care centres in the
      Management Area no. 5 Costa del Ponent. DESIGN: The study is descriptive and
      synchronic. LOCATION: The study was carried out at primary health care level, at
      the audiometry test services in the Management Area no. 5 Costa del Ponent.
      PATIENTS AND OTHER PARTICIPANTS: 2,366 audiometry tests were carried out over a
      period of three months. A study was performed of 1,152 patients presenting the
      conditions necessary for inclusion in the study: age over 16 years and presenting
      a hearing loss greater than 30 dB over any frequencies. All the participants were
      given a questionnaire investigating the risk factors involved in their hearing
      difficulty, in particular those relating to the workplace. FIGURES AND PRINCIPAL
      RESULTS: 269 (23.4%) of those in the study present hearing curves compatible with
      hearing loss due to noise. 501 participants declared themselves to be subject to
      work' place noise, and of those 247 (49.3%) present hearing curves compatible
      with hearing loss due to noise. CONCLUSIONS: The results of the study suggests
      that the health system should pay attention to workplace pathology and points out
      the need to develop action programmes which may permit an adequate response to
      the problem: specific systems should be established for detection of and
      information about workplace diseases, together with sufficient support at
      different levels of attendance to make such systems effective; training
      programmes should be set up for health workers in the area of workplace health
      for health workers.

PMID- 16986246
TI  - [Pulmonary hypertension: approximation to diagnosis in general practice].
AB  - Pulmonary hypertension is a syndrome which presents a wide variety of etiology
      and pathogens. Being able to reach an approximate diagnosis on the basis of
      clinical data and means available in general practice will permit an early
      diagnosis and therapeutic orientation.

PMID- 16986247
TI  - [Diagnostic attitude in chronic diarrhoea].

PMID- 16986248
TI  - [Ultrasound scan of the liver, bile duct and pancreas].

PMID- 16986249
TI  - [A critical analysis of intervention in cardiovascular risk factors].

PMID- 16986250
TI  - [Arthrocentesis].

PMID- 16986251
TI  - [Peripheral facial paralysis and the herpes chickenpox-zoster virus].

PMID- 16986252
TI  - Evolutionary design on a budget: robustness and optimality of bacteriophage T7.
AB  - Exploring how biological systems have been 'designed' by evolution to achieve
      robust behaviours is now a subject of increasing research effort. Yet, it still
      remains unclear how environmental factors may contribute to this process. This
      issue is addressed by employing a detailed computer model for the intracellular
      growth of phage T7. More than 150 000 in silico T7 mutants were generated and the
      rates and efficiencies of their growth in two host environments, namely, a
      realistic environment that offered finite host resources for the synthesis of
      phage functions and a hypothetical environment where the phage was supplied
      infinite host resources, were evaluated. Results revealed two key properties of
      phage T7. First, T7 growth was overall robust with respect to perturbations in
      its parameters, but fragile with respect to changes in the ordering of its
      genetic elements. Secondly, the wild-type T7 had close to optimal fitness in the
      finite environment. Furthermore, a strong correlation was found between fitness
      and growth efficiency in the finite environment. The results underscore the
      potential importance of the environment in shaping robust design of a biological
      system. In particular, the strong correlation between fitness and growth
      efficiency suggests that T7 may have evolved to maximise its growth rate by
      minimising waste of finite resources.

PMID- 16986253
TI  - Deterministic modelling and stochastic simulation of biochemical pathways using
      MATLAB.
AB  - The analysis of complex biochemical networks is conducted in two popular
      conceptual frameworks for modelling. The deterministic approach requires the
      solution of ordinary differential equations (ODEs, reaction rate equations) with
      concentrations as continuous state variables. The stochastic approach involves
      the simulation of differential-difference equations (chemical master equations,
      CMEs) with probabilities as variables. This is to generate counts of molecules
      for chemical species as realisations of random variables drawn from the
      probability distribution described by the CMEs. Although there are numerous tools
      available, many of them free, the modelling and simulation environment MATLAB is
      widely used in the physical and engineering sciences. We describe a collection of
      MATLAB functions to construct and solve ODEs for deterministic simulation and to
      implement realisations of CMEs for stochastic simulation using advanced MATLAB
      coding (Release 14). The program was successfully applied to pathway models from
      the literature for both cases. The results were compared to implementations using
      alternative tools for dynamic modelling and simulation of biochemical networks.
      The aim is to provide a concise set of MATLAB functions that encourage the
      experimentation with systems biology models. All the script files are available
      from www.sbi.uni-rostock.de/ publications_matlab-paper.html.

PMID- 16986254
TI  - New analysis technique for multistability detection.
AB  - Systems with counter-clockwise input-output (I-O) dynamics were recently
      introduced in order to study the convergence of positive feedback loops (possibly
      to many different equilibrium states). The author shows how this notion can be
      used to perform bifurcation analysis and globally predict multistability of a
      closed-loop feedback interconnection just by using the knowledge of steady-state
      I-O responses of the systems. To illustrate the theory, this method is then
      applied to a recently published model of mitogen activated protein kinase (MAPK)
      cascade. Furthermore, some examples (mainly motivated by molecular biology) of
      systems that enjoy the property are presented and discussed.

PMID- 16986255
TI  - Multi-class cancer classification using multinomial probit regression with
      Bayesian gene selection.
AB  - We consider the problems of multi-class cancer classification from gene
      expression data. After discussing the multinomial probit regression model with
      Bayesian gene selection, we propose two Bayesian gene selection schemes: one
      employs different strongest genes for different probit regressions; the other
      employs the same strongest genes for all regressions. Some fast implementation
      issues for Bayesian gene selection are discussed, including preselection of the
      strongest genes and recursive computation of the estimation errors using QR
      decomposition. The proposed gene selection techniques are applied to analyse real
      breast cancer data, small round blue-cell tumours, the national cancer
      institute's anti-cancer drug-screen data and acute leukaemia data. Compared with
      existing multi-class cancer classifications, our proposed methods can find which
      genes are the most important genes affecting which kind of cancer. Also, the
      strongest genes selected using our methods are consistent with the biological
      significance. The recognition accuracies are very high using our proposed
      methods.

PMID- 16986256
TI  - Automated sensitivity analysis of stiff biochemical systems using a fourth-order
      adaptive step size Rosenbrock integration method.
AB  - Sensitivity analysis is one of the most effective approaches for studying
      mathematical models of biochemical systems. A stiff Rosenbrock integrator has
      been developed for sensitivity analysis using a direct sensitivity approach.
      Automated sparse Jacobian and Hessian calculations of the coupled system (the
      original model equations and the sensitivity equations) have been implemented in
      the freely available software package CellSim. The accuracy and efficiency of the
      integrator are tested extensively on the complex mitogen-activated protein kinase
      (MAPK) pathway model of Bhalla and Iyengar. Both time-dependent concentration and
      parameter-based sensitivity coefficients are measured using several integration
      schemes. The method is shown to perform sensitivity analysis in a manner that is
      cost effective with moderate accuracy. The error control strategy between the
      decoupled direct method and the Rosenbrock with direct method is discussed and
      their computational accuracies are compared. The method is used to analyse the
      positive feedback loop within the MAPK signal transduction pathway.

PMID- 16986257
TI  - Systems biology, connectivity and the future of medicine.
AB  - The concept of systems-based strategies in medicine is emerging, with systems
      pathology guiding an understanding of the multidimensional aspects of disease
      system fingerprints and systems pharmacology providing insight into dynamic
      system responses upon (multiple) drug perturbations. Knowledge of the changes of
      system characteristics during disease progression creates a framework for the
      design of novel combinatorial treatment strategies. Such a systems-based,
      combinatorial-therapies approach readdresses the value of the synergistic actions
      of components of treatments based on natural products and highlights new
      methodology to study multidimensional intervention via reversed-pharmacology.

PMID- 16986258
TI  - Highly optimised global organisation of metabolic networks.
AB  - High-level, mathematically precise descriptions of the global organisation of
      complex metabolic networks are necessary for understanding the global structure
      of metabolic networks, the interpretation and integration of large amounts of
      biologic data (sequences, various -omics) and ultimately for rational design of
      therapies for disease processes. Metabolic networks are highly organised to
      execute their function efficiently while tolerating wide variation in their
      environment. These networks are constrained by physical requirements (e.g.
      conservation of energy, redox and small moieties) but are also remarkably robust
      and evolvable. The authors use well-known features of the stoichiometry of
      bacterial metabolic networks to demonstrate how network architecture facilitates
      such capabilities, and to develop a minimal abstract metabolism which
      incorporates the known features of the stoichiometry and respects the constraints
      on enzymes and reactions. This model shows that the essential functionality and
      constraints drive the tradeoffs between robustness and fragility, as well as the
      large-scale structure and organisation of the whole network, particularly high
      variability. The authors emphasise how domain-specific constraints and tradeoffs
      imposed by the environment are important factors in shaping stoichiometry.
      Importantly, the consequence of these highly organised tradeoffs and tolerances
      is an architecture that has a highly structured modularity that is self
      dissimilar and scale-rich.

PMID- 16986259
TI  - Accounting for quiescent cells in tumour growth and cancer treatment.
AB  - A four-state cell-cycle model with explicit G1-phase representation, termed the
      quiescent-cell model (QCM), has been proposed to represent biologically the G1
      phase specific effect of the chemotherapeutic tamoxifen. The QCM was used to
      model untreated and tamoxifen-treated tumour xenograft data from the literature
      with equivalent accuracy to previously developed tumour growth models. Open-loop
      analysis demonstrated that perturbations to the two newly introduced parameters,
      kG01 and kG10, significantly altered untreated tumour growth predictions.
      However, the sensitivity did not carry over to closed-loop simulations, where
      alterations to kD and kGS proved most significant in determining overall
      controller performance. Additional mismatch studies comparing controllers
      designed using the QCM to controllers designed with the Gompertz model and
      saturating-rate, cell-cycle model returned similar performance for a step-wise
      tumour reduction case study, but the quiescent-cell controller delivered a more
      aggressive treatment regimen. More importantly, the Gompertz and saturating-rate,
      cell-cycle controllers were unable to follow a reference trajectory when
      measurement updates were made biweekly, with both controllers returning tamoxifen
      dose schedules alternating between the maximum and minimum allowable dose.

PMID- 16986260
TI  - Quantitative data generation for systems biology: the impact of randomisation,
      calibrators and normalisers.
AB  - Systems biology is an approach to the analysis and prediction of the dynamic
      behaviour of biological networks through mathematical modelling based on
      experimental data. The current lack of reliable quantitative data, especially in
      the field of signal transduction, means that new methodologies in data
      acquisition and processing are needed. Here, we present methods to advance the
      established techniques of immunoprecipitation and immunoblotting to more accurate
      and quantitative procedures. We propose randomisation of sample loading to
      disrupt lane correlations and the use of normalisers and calibrators for data
      correction. To predict the impact of each method on improving the data quality we
      used simulations. These studies showed that randomisation reduces the standard
      deviation of a smoothed signal by 55% +/- 10%, independently from most
      experimental settings. Normalisation with appropriate endogenous or external
      proteins further reduces the deviation from the true values. As the improvement
      strongly depends on the quality of the normaliser measurement, a criteria-based
      normalisation procedure was developed. Our approach was experimentally verified
      by application of the proposed methods to time course data obtained by the
      immunoblotting technique. This analysis showed that the procedure is robust and
      can significantly improve the quality of experimental data.

PMID- 16986261
TI  - Biological complexity and drug discovery: a practical systems biology approach.
AB  - Drugs fail in clinical studies most often from lack of efficacy or unexpected
      toxicities. These failures result from an inadequate understanding of drug action
      and follow, in part, from our dependence on drug discovery technologies that do
      not take into account the complexity of human disease biology. Biological systems
      exhibit many features of complex engineering systems, including modularity,
      redundancy, robustness, and emergent properties. Addressing these features has
      contributed to the successful design of an improved biological assay technology
      for inflammation drug discovery. This approach, termed Biologically Multiplexed
      Activity Profiling (BioMAP), involves the statistical analysis of protein
      datasets generated from novel complex primary human cell-based assay systems.
      Compound profiling in these systems has revealed that a surprisingly large number
      of biological mechanisms can be detected and distinguished. Features of these
      assays relevant to the behaviour of complex systems are described.

PMID- 16986262
TI  - Smooth bistable S-systems.
AB  - S-systems have been used as models of biochemical systems for over 30 years. One
      of their hallmarks is that, although they are highly non-linear, their steady
      states are characterised by linear equations. This allows streamlined analyses of
      stability, sensitivities and gains as well as objective, mathematically
      controlled comparisons of similar model designs. Regular S-systems have a unique
      steady state at which none of the system variables is zero. This makes it
      difficult to represent switching phenomena, as they occur, for instance, in the
      expression of genes, cell cycle phenomena and signal transduction. Previously,
      two strategies were proposed to account for switches. One was based on a
      technique called recasting, which permits the modelling of any differentiable non
      linearities, including bistability, but typically does not allow steady-state
      analyses based on linear equations. The second strategy formulated the switching
      system in a piece-wise fashion, where each piece consisted of a regular S-system.
      A representation gleaned from a simplified form of recasting is proposed and it
      is possible to divide the characterisation of the steady states into two phases,
      the first of which is linear, whereas the other is non-linear, but easy to
      execute. The article discusses a representative pathway with two stable states
      and one unstable state. The pathway model exhibits strong separation between the
      stable states as well as hysteresis.

PMID- 16986263
TI  - Application of predictive biosimulation within pharmaceutical clinical
      development: examples of significance for translational medicine and clinical
      trial design.
AB  - The challenge of accurately predicting human clinical outcome based on
      preclinical data has led to a high failure rate of compounds in human clinical
      trials. A series of methods are described by which biosimulation can address
      these challenges and guide the design and evaluation of experimental and clinical
      protocols. Early compound development often proceeds on the basis of preclinical
      data from animal models. The systematic evaluation possible in a simulation can
      assist in the critical step of translating the preclinical outcomes to human
      physiology. Later in the process, clinical trials definitively establish a
      therapy's beneficial effects, as well as any adverse side effects. Biosimulation
      allows for the optimal design of clinical trials to ensure that key issues are
      addressed effectively and efficiently, and in doing so, improves the success rate
      of the trials.

PMID- 16986264
TI  - Robustness properties of apoptosis models with respect to parameter variations
      and intrinsic noise.
AB  - Analyses of different robustness aspects for models of the direct signal
      transduction pathway of receptor-induced apoptosis is presented. Apoptosis is a
      form of programmed cell death, removing unwanted cells within multicellular
      organisms to maintain a proper balance between cell reproduction and death. Its
      signalling pathway includes an activation feedback loop that generates bistable
      behaviour, where the two steady states can be seen as 'life' and 'death'.
      Inherent robustness, widely recognised in biological systems, is of major
      importance in apoptosis signalling, as it guarantees the same cell fate for
      similar conditions. First, the influence of the stochastic nature of reactions
      indicating a role for inhibition reactions as noise filters and justifying a
      deterministic approach in the further analyses is evaluated. Second, the
      robustness of the bistable threshold with respect to parameter changes is
      evaluated by statistical methods, showing the need to balance both the forward
      and the back part of the activation loop. These analyses can also discriminate
      between the models favouring the model consistent with novel biological findings.
      The parameter robustness analyses are also applicable to other signal
      transduction networks, as several have been shown to display bistable behaviour.
      These methods therefore have a range of possible applications in systems biology
      not only to measure robustness, but also for model discrimination.

PMID- 16986266
TI  - Using chemical reaction network theory to discard a kinetic mechanism hypothesis.
AB  - Feinberg's chemical reaction network theory (CRNT) connects the structure of a
      biochemical reaction network to qualitative properties of the corresponding
      system of ordinary differential equations. No information about parameter values
      is needed. As such, it seems to be well suited for application in systems
      biology, where parameter uncertainty is predominant. However, its application in
      this area is rare. To demonstrate the potential benefits from its application,
      different reaction networks representing a single layer of the well-studied
      mitogen-activated protein kinase (MAPK) cascade are analysed. Recent results from
      Markevich et al. (2004) show that, unexpectedly, multilayered protein kinase
      cascades can exhibit multistationarity, even on a single cascade level. Using
      CRNT, we show that their assumption of a distributive mechanism for double
      phosphorylation and dephosphorylation is crucial for multistationarity on the
      single cascade level.

PMID- 16986265
TI  - Reduced-order modelling of biochemical networks: application to the GTPase-cycle
      signalling module.
AB  - Biochemical systems embed complex networks and hence development and analysis of
      their detailed models pose a challenge for computation. Coarse-grained
      biochemical models, called reduced-order models (ROMs), consisting of essential
      biochemical mechanisms are more useful for computational analysis and for
      studying important features of a biochemical network. The authors present a novel
      method to model-reduction by identifying potentially important parameters using
      multidimensional sensitivity analysis. A ROM is generated for the GTPase-cycle
      module of m1 muscarinic acetylcholine receptor, Gq, and regulator of G-protein
      signalling 4 (a GTPase-activating protein or GAP) starting from a detailed model
      of 48 reactions. The resulting ROM has only 17 reactions. The ROM suggested that
      complexes of G-protein coupled receptor (GPCR) and GAP--which were proposed in
      the detailed model as a hypothesis--are required to fit the experimental data.
      Models previously published in the literature are also simulated and compared
      with the ROM. Through this comparison, a minimal ROM, that also requires
      complexes of GPCR and GAP, with just 15 parameters is generated. The proposed
      reduced-order modelling methodology is scalable to larger networks and provides a
      general framework for the reduction of models of biochemical systems.

PMID- 16986267
TI  - Algorithmic approaches for computing elementary modes in large biochemical
      reaction networks.
AB  - The concept of elementary (flux) modes provides a rigorous description of
      pathways in metabolic networks and proved to be valuable in a number of
      applications. However, the computation of elementary modes is a hard
      computational task that gave rise to several variants of algorithms during the
      last years. This work brings substantial progresses to this issue. The authors
      start with a brief review of results obtained from previous work regarding (a) a
      unified framework for elementary-mode computation, (b) network compression and
      redundancy removal and (c) the binary approach by which elementary modes are
      determined as binary patterns reducing the memory demand drastically without loss
      of speed. Then the authors will address herein further issues. First, a new way
      to perform the elementarity tests required during the computation of elementary
      modes which empirically improves significantly the computation time in large
      networks is proposed. Second, a method to compute only those elementary modes
      where certain reactions are involved is derived. Relying on this method, a
      promising approach for computing EMs in a completely distributed manner by
      decomposing the full problem in arbitrarity many sub-tasks is presented. The new
      methods have been implemented in the freely available software tools FluxAnalyzer
      and Metatool and benchmark tests in realistic networks emphasise the potential of
      our proposed algorithms.

PMID- 16986268
TI  - Systems biology for battling rheumatoid arthritis: application of the Entelos
      PhysioLab platform.
AB  - A large-scale mathematical model, the Entelos Rheumatoid Arthritis (RA) PhysioLab
      platform, has been developed to describe the inflammatory and erosive processes
      in afflicted joints of people suffering from RA. The platform represents the life
      cycle of inflammatory cells, endothelium, synovial fibroblasts, and chondrocytes,
      as well as their products and interactions. The interplay between these processes
      culminates in clinically relevant measures for inflammation and erosion. The
      simulation model is deterministic, which allows tracing back the mechanism of
      action for a particular simulation result. Different patient phenotypes are
      represented by different virtual patients. The RA PhysioLab platform has been
      used to systematically and quantitatively study the predicted therapeutic effect
      of modulating several molecular targets, which resulted in a ranking of putative
      drug targets and a workflow to confirm the simulations experimentally. In
      addition, critical pathways were identified that drive the predicted disease
      outcome. Within these pathways, targets were identified from public literature
      that were not previously associated with arthritis. The model provides insights
      into the biology of RA and can be used as a platform for hypothesis-driven
      research. Case studies of therapies directed against IL-12 and IL-15 illustrate
      the approach, with emphasis on the analysis of system dynamics.

PMID- 16986269
TI  - Differential coding of humoral stimuli by timing and amplitude of intracellular
      calcium spike trains.
AB  - The ubiquitous Ca2(+)-phosphoinositide pathway transduces extracellular signals
      to cellular effectors. Using a mathematical model, we simulated intracellular
      Ca2+ fluctuations in hepatocytes upon humoral stimulation. We estimated the
      information encoded about random humoral stimuli in these Ca2+ spike trains using
      an information-theoretic approach based on stimulus estimation methods. We
      demonstrate accurate transfer of information about random humoral signals with
      low temporal cutoff frequencies. In contrast, our results suggest that high
      frequency stimuli are poorly transduced by the transmembrane machinery. We found
      that humoral signals are encoded in both the timing and amplitude of
      intracellular Ca2+ spikes. The information transmitted per spike is similar to
      that of sensory neuronal systems, in spite of several orders of magnitude
      difference in firing rate.

PMID- 16986270
TI  - Establishing a master's degree programme in bioinformatics: challenges and
      opportunities.
AB  - The development of the Bioinformatics MS degree program at the University of
      Illinois, the challenges and opportunities associated with such a process, and
      the current structure of the program is described. This program has departed from
      earlier University practice in significant ways. Despite the existence of several
      interdisciplinary programs at the University, a few of which grant degrees, this
      is the first interdisciplinary program that grants degrees and formally
      recognises departmental specialisation areas. The program, which is not owned by
      any particular department but by the Graduate College itself, is operated in a
      franchise-like fashion via several departmental concentrations. With four
      different colleges and many more departments involved in establishing and
      operating the program, the logistics of the operation are of considerable
      complexity but result in significant interactions across the entire campus.

PMID- 16986271
TI  - Systems-level questions in Drosophila oogenesis.
AB  - This paper describes computational and experimental work on pattern formation in
      Drosophila egg development (oogenesis), an established experimental model for
      studying cell fate diversification in developing tissues. Epidermal growth factor
      receptor (EGFR) is a key regulator of pattern formation and morphogenesis in
      Drosophila oogenesis. EGFR signalling in oogenesis can be genetically manipulated
      and monitored at many levels, leading to large sets of heterogeneous data that
      enable the formulation of increasingly quantitative models of pattern formation
      in these systems.

PMID- 16986272
TI  - Analysis of cellular response to protein overexpression.
AB  - The overexpression of secreted proteins is of critical importance to the
      biotechnology and biomedical fields. A common roadblock to high yields of
      proteins is in the endoplasmic reticulum (ER) where proofreading for properly
      folded proteins is often rate limiting. Heterologous expression of secreted
      proteins can saturate the cell's capacity to properly fold protein, initiating
      the unfolded protein response (UPR), and resulting in a loss of protein
      expression. An obvious method for overcoming this block would be to increase the
      capacity of the folding process (overexpressing chaperones) or decreasing the
      proofreading process (blocking the down-regulation by the UPR). Unfortunately,
      these processes are tightly interlinked, whereby modification of one mechanism
      has unknown effects on the other. Although some success has been achieved in
      improving expression via co-overexpressing ER chaperones, the results have not
      lead to a global method for increasing all heterologously overexpressed proteins.
      Further, many diseases have been linked to extended periods of stress and are not
      treatable by these approaches. This work utilises both experimental analysis of
      the interactions within the ER and modelling in order to understand how these
      interactions affect early secretory pathway dynamics. This study shows that
      overexpression of the ER chaperone binding protein does not regulate Ire1p and
      the UPR as predicted by a model based on the published understanding of the
      molecular mechanism. A new model is proposed for Ire1p regulation and the UPR
      that better fits the experimental data and recent studies on Ire1p.

PMID- 16986273
TI  - Systems biology and the mathematical modelling of antibody-directed enzyme
      prodrug therapy (ADEPT).
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) can generate highly localised
      concentrations of cytotoxic agents directly in a tumour, thereby reducing the
      collateral toxicity associated with normal tissue exposure. ADEPT is a two
      component approach. First, a non-toxic antibody-enzyme fusion protein is
      localised in the tumour matrix by binding a specific antigen expressed only on
      the surface of a cancer cell. Once the fusion protein is bound, an inert small
      molecule prodrug is administered which is the substrate for the enzyme bound to
      the tumour surface. When the prodrug comes into contact with the bound enzyme, an
      active cytotoxic agent is generated. A multiple length-scale model of ADEPT
      therapy in solid tumours is presented. A four-compartment pharmacokinetic (PK)
      model is formulated where the tumour is comprised of interstitial and cell
      surface subcompartments. The macroscopic PK model which describes the
      biodistribution of antibody-enzyme conjugate, prodrug and active drug at the
      largest length scale is coupled to a reaction-diffusion tumour model. The models
      are qualitatively validated against current literature and experimental
      understanding. The relationship between tumour localisation and the affinity of
      the antibody-enzyme conjugate for its surface antigen is explored by simulation.
      The influence of pharmacokinetic and biophysical parameters such as renal
      elimination rate and permeability of the tumour vasculature upon tumour uptake
      and retention of the fusion protein are also explored. Lastly, a technique for
      establishing an optimal prodrug dosing schedule is formulated and initial
      simulation results are presented.

PMID- 16986274
TI  - Biochemical networks with uncertain parameters.
AB  - The modelling of biochemical networks becomes delicate if kinetic parameters are
      varying, uncertain or unknown. Facing this situation, we quantify uncertain
      knowledge or beliefs about parameters by probability distributions. We show how
      parameter distributions can be used to infer probabilistic statements about
      dynamic network properties, such as steady-state fluxes and concentrations,
      signal characteristics or control coefficients. The parameter distributions can
      also serve as priors in Bayesian statistical analysis. We propose a graphical
      scheme, the 'dependence graph', to bring out known dependencies between
      parameters, for instance, due to the equilibrium constants. If a parameter
      distribution is narrow, the resulting distribution of the variables can be
      computed by expanding them around a set of mean parameter values. We compute the
      distributions of concentrations, fluxes and probabilities for qualitative
      variables such as flux directions. The probabilistic framework allows the study
      of metabolic correlations, and it provides simple measures of variability and
      stochastic sensitivity. It also shows clearly how the variability of biological
      systems is related to the metabolic response coefficients.

PMID- 16986275
TI  - p53-Mdm2 loop controlled by a balance of its feedback strength and effective
      dampening using ATM and delayed feedback.
AB  - When the genomic integrity of a cell is challenged, its fate is determined in
      part by signals conveyed by the p53 tumour suppressor protein. It was observed
      recently that such signals are not simple gradations of p53 concentration, but
      rather a counter-intuitive limit-cycle behaviour. Based on a careful mathematical
      interpretation of the experimental body of knowledge, we propose a model for the
      p53 signalling network and characterise the p53 stability and oscillatory
      dynamics. In our model, ATM, a protein that senses DNA damage, activates p53 by
      phosphorylation. In its active state, p53 has a decreased degradation rate and an
      enhanced transactivation of Mdm2, a gene whose protein product Mdm2 tags p53 for
      degradation. Thus the p53-Mdm2 system forms a negative feedback loop. However,
      the feedback in this loop is delayed, as the pool of Mdm2 molecules being induced
      by p53 at a given time will mark for degradation the pool of p53 molecules at
      some later time, after the Mdm2 molecules have been transcribed, exported out of
      the nucleus, translated and transported back into the nucleus. The analysis of
      our model demonstrates how this time lag combines with the ATM-controlled
      feedback strength and effective dampening of the negative feedback loop to
      produce limit-cycle oscillations. The picture that emerges is that ATM, once
      activated by DNA damage, makes the p53-Mdm2 oscillator undergo a supercritical
      Hopf bifurcation. This approach yields an improved understanding of the global
      dynamics and bifurcation structure of our time-delayed, negative feedback model
      and allows for predictions of the behaviour of the p53 system under different
      perturbations.

PMID- 16986276
TI  - Mathematical and computational modelling of spatio-temporal signalling in rod
      phototransduction.
AB  - Rod photoreceptors are activated by light through activation of a cascade that
      includes the G protein-coupled receptor rhodopsin, the G protein transducin, its
      effector cyclic guanosine monophosphate (cGMP) phosphodiesterase and the second
      messengers cGMP and Ca2+. Signalling is localised to the particular rod outer
      segment disc, which is activated by absorption of a single photon. Modelling of
      this cascade has previously been performed mostly by assumption of a well-stirred
      cytoplasm. We recently published the first fully spatially resolved model that
      captures the local nature of light activation. The model reduces the complex
      geometry of the cell to a simpler one using the mathematical theories of
      homogenisation and concentrated capacity. The model shows that, upon activation
      of a single rhodopsin, changes of the second messengers cGMP and Ca2+ are local
      about the particular activated disc. In the current work, the homogenised model
      is computationally compared with the full, non-homogenised one, set in the
      original geometry of the rod outer segment. It is found to have an accuracy of
      0.03% compared with the full model in computing the integral response and a 5200
      fold reduction in computation time. The model can reconstruct the radial time
      profiles of cGMP and Ca2+ in the interdiscal spaces adjacent to the activated
      discs. Cellular electrical responses are localised near the activation sites, and
      multiple photons sufficiently far apart produce essentially independent
      responses. This leads to a computational analysis of the notion and estimate of
      'spread' and the optimum distribution of activated sites that maximises the
      response. Biological insights arising from the spatio-temporal model include a
      quantification of how variability in the response to dim light is affected by the
      distance between the outer segment discs capturing photons. The model is thus a
      simulation tool for biologists to predict the effect of various factors
      influencing the timing, spread and control mechanisms of this G protein-coupled,
      receptor-mediated cascade. It permits ease of simulation experiments across a
      range of conditions, for example, clamping the concentration of calcium, with
      results matching analogous experimental results. In addition, the model
      accommodates differing geometries of rod outer segments from different vertebrate
      species. Thus it represents a building block towards a predictive model of visual
      transduction.

PMID- 16986277
TI  - Effects of RNA splicing and post-transcriptional regulation on HIV-1 growth: a
      quantitative and integrated perspective.
AB  - Despite major advances over the last two decades in our understanding of RNA
      splicing and (post-) transcriptional regulation in human immunodeficiency virus
      type-1 (HIV-1), debate continues on the mechanisms and effects of Rev protein on
      HIV-1 growth. Moreover, arguments that HIV-1 has been optimised for growth have
      been largely based on speculation. Here, we begin systematically to address these
      issues by developing a detailed kinetic model for HIV-1 intracellular
      development. The model accounts for transcription, successive steps in RNA
      splicing, nuclear export of mRNAs, translation and shuttling of Rev and Tat, Tat
      mediated transactivation of transcription, thresholds on Rev in its effects on
      nuclear export of mRNA, and inhibitory effects of Rev on splicing. Using the
      model, we found that inefficient splicing of HIV-1 mRNA was generally beneficial
      for HIV-1 growth, but that an excessive reduction in the splicing efficiency
      could be detrimental, suggesting that there exists a splicing efficiency that
      optimises HIV-1 growth. Further, we identified two key contributors to splicing
      efficiency, the intrinsic splicing rate and the extent of Rev-mediated splicing
      inhibition, and we showed how these should be balanced for HIV-1 to optimise its
      growth. Finally, we found that HIV-1 growth is relatively insensitive to
      different levels of the Rev export threshold, and we suggest that this mechanism
      evolved to delay viral growth, perhaps to enable evasion of host defensive
      responses. In summary, our model provides a quantitative and qualitative
      framework for probing how constituent mechanisms contribute to the complex, yet
      logical, process of HIV-1 growth.

PMID- 16986278
TI  - Synergistic control of oscillations in the NF-kappaB signalling pathway.
AB  - In previous work, we studied the behaviour of a model of part of the NF-kappaB
      signalling pathway. The model displayed oscillations that varied both in number,
      amplitude and frequency when its parameters were varied. Sensitivity analysis
      showed that just nine of the 64 reaction parameters were mainly responsible for
      the control of the oscillations when these parameters were varied individually.
      However, the control of the properties of any complex system is distributed, and,
      as many of these reactions are highly non-linear, we expect that their
      interactions will be too. Pairwise modulation of these nine parameters gives a
      search space some 50 times smaller (81 against 4096) than that required for the
      pairwise modulation of all 64 reactions, and this permitted their study (which
      would otherwise have been effectively intractable). Strikingly synergistic
      effects were observed, in which the effect of one of the parameters was strongly
      (and even qualitatively) dependent on the values of another parameter. Regions of
      parameter space could be found in which the amplitude, but not the frequency
      (timing), of oscillations varied, and vice versa. Such modelling will permit the
      design and performance of experiments aimed at disentangling the role of the
      dynamics of oscillations, rather than simply their amplitude, in determining cell
      fate. Overall, the analyses reveal a level of complexity in these dynamic models
      that is not apparent from study of their individual parameters alone and point to
      the value of manipulating multiple elements of complex networks to achieve
      desired physiological effects.

PMID- 16986279
TI  - Improved parameter estimation for systems with an experimentally located Hopf
      bifurcation.
AB  - When performing system identification, we have two sources of information:
      experimental data and prior knowledge. Many cell-biological systems are
      oscillating, and sometimes we know an input where the system reaches a Hopf
      bifurcation. This is the case, for example, for glycolysis in yeast cells and for
      the Belousov-Zhabotinsky reaction, and for both of these systems there exist
      significant numbers of quenching data, ideal for system identification. We
      present a method that includes prior knowledge of the location of a Hopf
      bifurcation in estimation based on time-series. The main contribution is a
      reformulation of the prior knowledge into the standard formulation of a
      constrained optimisation problem. This formulation allows for any of the standard
      methods to be applied, including all the theories regarding the method's
      properties. The reformulation is carried out through an over-parametrisation of
      the original problem. The over-parametrisation allows for extra constraints to be
      formed, and the net effect is a reduction of the search space. A method that can
      solve the new formulation of the problem is presented, and the advantage of
      adding the prior knowledge is demonstrated on the Brusselator.

PMID- 16986280
TI  - Prevalence of gestrointestinal symptoms in pregnancy.
AB  - OBJECTIVES: This study is aimed at determining the prevalence of gastrointestinal
      symptoms among healthy pregnant women attending antenatal clinic at the
      University of Maiduguri Teaching Hospital. METHODS: Questionnaires were randomly
      administered to consecutive antenatal clinic attendees until the sample size was
      reached. RESULTS: Three hundred and seventy pregnant women were interviewed.
      Heart burns, easy fullness and nausea were the commonest gastrointestinal
      symptoms in 45%, 40.2% and 39.9% of cases respectively. Primigravidae had
      significantly more symptoms than multiparae. There were also significantly more
      gastrointestinal symptoms in the first trimester of pregnancy. CONCLUSION:
      Gastrointestinal symptoms are common among healthy pregnant women. And even
      though these represent well-known physiological changes, they must be carefully
      assessed to exclude any pathological disorder that may require intervention.

PMID- 16986281
TI  - Hepatitis B vaccination status among health workers in Enugu, Nigeria.
AB  - BACKGROUND: Health workers in Nigeria are particularly at increased risk of
      contracting hepatitis B virus in their work place because Nigeria is a
      holoendemic area. Hepatitis B vaccination virtually eliminates this risk. There
      are few studies on the perception and uptake of hepatitis B vaccination among
      health workers in Nigeria and none to our knowledge in the University of Nigeria
      Teaching Hospital (UNTH), Enugu. OBJECTIVE: To determine the Hepatitis B
      vaccination level among all categories of health workers in UNTH, Enugu, and the
      factors that influence its uptake. METHOD: The study was cross-sectional in
      design. Subjects were health workers likely to be exposed to patients and or
      their body fluids. The tool was a self administered pre-tested questionnaire and
      analysis was done using SPSS version 11.5 software. RESULTS: Fifty point four
      percent of the health workers felt that their jobs exposed them to an increased
      risk of contracting hepatitis B virus infection. There is a significant
      occupational difference in perception with only 5.5% of the ward attendants as
      against 67.9% of other workers feeling that their jobs exposed them to increased
      risk (P = 0.00). Twenty two point four percent had received Hepatitis B
      vaccination, 3.7% had received 3 or more doses. Only years of occupational
      practice had a significant influence on vaccination uptake (P = 0.00). The most
      common reason for non-vaccination was lack of opportunity (43.08%). Among the
      53.7% of the respondents who had had needle stick injury, none received post
      exposure prophylaxis. CONCLUSION: There is a low level of hepatitis B vaccination
      and no post exposure prophylaxis among health workers in UNTH, Enugu. This is due
      to poor perception of the risk of contracting this infection and non-availability
      of the vaccines.

PMID- 16986282
TI  - Knowledge and attitude of youth (ages 15-25 years) to HIV/AIDS and to routine HIV
      screening.
AB  - BACKGROUND: AIDS is still an incurable disease and is very costly to control.
      Since the first case of Acquired Immune Deficiency Syndrome (AIDS) in Nigeria was
      reported in 1986, the human immune deficiency virus (HIV) infection has attained
      epidemic proportion. In an effort to control this rapid spread, certain
      preventive measures have been developed. In spite of these and the campaigns to
      control it, the knowledge and attitudes of youths towards HIV/AIDS leaves much to
      be desired. OBJECTIVE: To determine knowledge and attitude of youths (15 - 25
      years) of HIV/AIDS and to Routine HIV Screening. STUDY DESIGN: The study was
      cross-sectional. SETTING: The study was carried out at the University of Benin
      Teaching Hospital, Benin City, Nigeria, between January and December 2003.
      RESULTS: Five thousand three hundred and twenty STUDY POPULATION: The knowledge
      and attitude of youths (15 - 25 years) of HIV/AIDS and to routine HIV screening
      was assessed, using anonymous questionnaires, among 9500 respondents, 4950 males
      and 4550 females. 5750 respondents were from the University of Benin with a
      population of 20,000 students while 3750 were from some of the Secondary Schools
      (post primary Schools) randomly selected in Benin City, Nigeria. The University
      of Benin Teaching Hospital where the work was done is adjacent to the University
      of Benin. The Secondary Schools selected where the work was done were within a
      radius of 20 kilometers of the Teaching Hospital and were 5 in numbers with
      average of 750 students selected per school. Subjects (56%) indicated that they
      have heard about HIV/AIDS, 4180 (44%) had no knowledge of HIV/AIDS at all. 2240
      of 5320 (42.1%) had some knowledge; 1593 (29.9%) had adequate knowledge and only
      1487 (28.0%) had sufficient knowledge. 6365 (67%) did not believe it exists and
      as a result they are not bothered by it. 825 of the 3750 secondary school
      students had multiple sexual partners. Majority had single partners for those who
      had at all. While among the University students 2990 (52%) had multiple sexual
      partners, while others had between one and two sexual partners. Only 36210 (38%)
      believe it is real and a killer disease frightened about it and are already
      changing their sexual behaviours; 1900 (20%) believe it is a western propaganda
      to enslave the developing world. Three thousand nine hundred and ninety
      respondents (42%) would agree to routine HIV screening and 5510 (58%) would not
      agree to routine screening. The reasons adduced for rejecting routine HIV
      screening included psychological trauma, not necessarily high cost of and lack of
      anti-retroviral drugs, infringement on fundamental human rights, fear of living
      with positive screening, stigmatization and victimization at place of work if
      positive. CONCLUSION: Intensive massive awareness campaign through Radio,
      Televisions jingles and education about HIV/AIDS of the population is recommended
      to alter their current negative attitude to routine HIV testing and increase
      their knowledge about HIV/AIDS and perhaps help to change their sexual
      behaviours.

PMID- 16986283
TI  - Epidemiology of malaria in infancy at Enugu, Nigeria.
AB  - This was a retrospective study to ascertain the prevalence and clinical features
      of malaria in infants in Enugu between January 1998 and January 2000. Case notes
      of two thousand children were reviewed, one hundred and fifty-five (7.75%) had a
      diagnosis of malaria, with a male/female ratio of 1.2:1. The age range was two
      days to twelve months with a mean of 5.06 +/- 3.24 months. Nine infants (5.8 %)
      were less than seven days old. Ninety-nine of the patients (63.9%) had
      temperature > or = 37.5 degrees C. Diarrhea was a symptom in 52 (33.5%) patients,
      while vomiting alone or in combination with diarrhea was a presenting feature in
      37 (23.87%) of the children. Twenty-eight children (18.1%) had respiratory
      symptoms of which, two had bronchopneumonia. Other associated illnesses included.
      septicaemia: 6(3.8%). infective diarrhea; 5(3.2%), and urinary tract infection; 4
      (2.6%). Malaria is common in infants less than 6 months of age and associated
      with symptoms common with other childhood illnesses.

PMID- 16986284
TI  - The risk of transfusion-acquired hepatitis-C virus infection among blood donors
      in Port Harcourt: the question of blood safety in Nigeria.
AB  - OBJECTIVE: This study was undertaken to establish the sero-epidemology of
      Hepatitis C Virus (HCV) antibodies among blood donors in Port Harcourt, Nigeria.
      METHODS: One Thousand Five Hundred consecutive blood donors presenting to the
      blood transfusion unit of the University of Port Harcourt Teaching Hospital
      between January and April, 2003 comprising of 1481 males and 19 females were
      screened for hepatitis C antibodies using the commercially available Clinotech
      anti-HCV test strips. All initially positive samples were subsequently tested
      using a second-generation Trinity Biotec enzyme linked immunosorbent assay.
      RESULTS: HCV antibodies were detected in 7 (0.5%) of donors. Although
      statistically not significant, the overall sero prevalence of HCV antibodies was
      higher in males 7 (0.5%) compared to zero prevalence among females. (chi-squared
      = 1.94, p = 1.000). Commercial remunerated donors had a higher prevalence of anti
      HCV anti-bodies 5 (0.8%) compared to family replacement donors (0.2%) (chi
      squared = 1.25, p = 0.26). The highest infection rate occurred in the 18 - 27
      years age group 7 (0.7%). CONCLUSION: This study shows a 0.5% prevalence of HCV
      antibodies among blood donors and describes their demographic characteristics.
      This calls for urgent implementation of a universal donor screening for HCV
      antibodies and setting up of a national blood transfusion service run on the
      basis of voluntary, non-remunerated low risk donors.

PMID- 16986285
TI  - Caesarean section in the management of singleton breech delivery in Calabar,
      Nigeria.
AB  - OBJECTIVE: To establish the role of Caesarean section in reducing perinatal
      mortality following singleton breech delivery in the University of Calabar
      Teaching Hospital, Calabar. METHOD: The case notes of all patients who had
      singleton breech delivery between 1st January 1991 and 31st December 2000 were
      studied. RESULTS: The incidence of singleton breech delivery was 1.4% and 37.1%
      of the breech deliveries were by Caesarean section. Feto-pelvic disproportion and
      footling breech presentation were the most common indications for Caesarean
      section (50.0%). Most of the breeches delivered by emergency Caesarean section
      (55.0%) were in unbooked patients while the booked ones were mostly delivered by
      elective Caesarean section (80.0%). There was a statistically significant
      decrease in perinatal mortality in primigravid breeches ((p = 0.018) and in
      fetuses estimated to weigh above 3.5 kilograms (p = 0.0005) following Caesarean
      section. CONCLUSION: This study shows that Caesarean section plays a very
      important role in the management of breech presentation in our environment. We
      advocate elective Caesarean section of all primigravid breeches and those whose
      fetuses are estimated to weigh above 3.5 kilograms.

PMID- 16986286
TI  - Sexual behaviour, contraception and fertility among in-school adolescents in
      Ikenne Local Government, south-western Nigeria.
AB  - A cross- sectional study was conducted among in-school adolescents in six
      secondary schools in the health districts of Ikenne Local Government to assess
      the sexual behaviour, contraception and fertility experiences of the adolescents
      between the months of May and November 2002.Relevant information was collected
      from 1140 in-school adolescents with the aid of pre-tested, structured, self
      administered questionnaires, selected by using multistage and stratified random
      sampling techniques Information sought from the questionnaires included socio
      demographic characteristics of the respondents, parental background, their sexual
      behaviour, knowledge and use of contraception, human development, pregnancy and
      fertility experiences, information on sexually transmitted infections (STIs) and
      HIV/AIDS. During the same period, twelve (12) Focus Group Discussions (FGDs)
      sessions were conducted using an FGD Guide in the selected schools to highlight
      differences in opinions of students and also to highlight identification of the
      group consensus. The mean ages at first intercourse were 13.9 +/- 2.8 years and
      14.8 +/- 2.4years for males and females respectively. Boys initiated sex earlier
      than girls. This difference was found to be statistically significant (p<0.05).
      Sexual intercourse had been experienced by 28.5% of the adolescent students,
      significantly more (37.6%) males than females (20.4%) The school adolescents that
      responded as being married were.4.5% (26males, 23 females) of the respondents.
      Knowledge on contraception was 36.9% and 22.1% for male and female students
      respectively, more males than females had knowledge of contraception in a
      significant proportion, apparently due to increase awareness of the male condom
      among males. Current use of contraception was equally low, and was found to be
      10.9% and 6.0% for males and females respectively. The reasons for non-use were
      mainly that of non-availability (22.3%), cost (11.8%) negative attitude towards
      contraception due to societal disapproval (33.2%) and lack of knowledge of how to
      use them (21.3%). The proportion of adolescents that had ever experienced
      symptoms associated with Sexually Transmitted Infections (STIs) was 26.8%.
      Multiple factors were found to be responsible for the deplorable reproductive
      health situation of the adolescents in this community. The need for provision of
      sexuality and life planning education in schools including the provision of Youth
      friendly health services in the community were highlighted.

PMID- 16986287
TI  - Relationship between knowledge of HIV/AIDS and sexual behaviour among in-school
      adolescents in Delta State, Nigeria.
AB  - OBJECTIVE: To determine if there is any correlation between the knowledge of
      HIV/AIDS among in-school adolescents in Delta state of Nigeria and their sexual
      behaviour. METHOD: A questionnaire based descriptive study of randomly selected
      secondary school students in Asaba. Delta state. RESULTS: A total of 437 students
      were recruited for the study. About 47% of respondents had good knowledge of
      HIV/AIDS. The electronic media were their main sources of information. Fifty
      eight percent had been sexually initiated but only 10% were currently sexually
      active. About 73% of the males and 58% of the females reported condom use in
      their last sexual act. Seventy-three percent of the students that had poor
      knowledge of HIV/AIDS had ever had sex compared with 69.5% of students with good
      knowledge. Similarly 45.6% of students with poor knowledge used condom compared
      with 58.8% who had good knowledge. However these observed differences were not
      statistically significant. CONCLUSION: Knowledge of HIV/AIDS by in-school
      adolescents in Asaba has not significantly influenced their sexual behavior.
      Program planners should explore and integrate other factors that could impact
      positively on adolescent sexual behavior.

PMID- 16986288
TI  - Knowledge, attitude and practice of cervical cancer screening (pap smear) among
      female nurses in Nnewi, South Eastern Nigeria.
AB  - OBJECTIVE: To determine the knowledge and practice of cervical cancer screening
      among practicing female nurses with a view to sensitizing them as a first step
      towards increasing screening uptake in the community. METHOD: A self administered
      questionnaire survey of all the female nurses working in Nnamdi Azikiwe
      university Teaching Hospital Nnewi center. RESULTS: 144 out of 166 questionnaires
      were correctly completed and returned. 122 (87%) were aware of the existence of
      screening services. Although 9.3% had lost relations to cancer of the cervix,
      only 5.7% had ever undergone a pap smear. While 52 (37.1%) had no reason for not
      screening, 21 (15%) were afraid of the possible outcome and 35 (25%) felt they
      were not likely candidates for cancer of the cervix. CONCLUSION: knowledge of
      cervical cancer screening services among female nurses in Nnewi is high while
      uptake rate is abysmally poor. There is need to further educate the nurses who
      will play a major role in enlightening the public on the availability and need
      for cervical screening services.

PMID- 16986289
TI  - Outcome of tubal surgeries at the University of Nigeria Teaching Hospital, Enugu,
      Nigeria.
AB  - OBJECTIVE: To determine the outcome of tubal surgeries at the University of
      Nigeria Teaching Hospital. Enugu, Nigeria over a 15 year period (1990 - 2004).
      METHOD: A retrospective case series review. RESULTS: Sixty-four women underwent
      tubal surgery in the hospital within the 15 year period. Hydrosalpinx was the
      most frequent tubal pathology occurring in 35 (54.7%) of the women followed by
      peritubal adhesions in 13 (20.3%) women and cornual block in 11 (17.2%) women.
      The surgical access was through laparotomy in 59 (92.2%) women and laparoscopy in
      5 (7.8%) women. Fifty-seven (89.1%) of the cases had macrotubal surgery while 7
      (10.9%) women had microtubal surgery. Twenty-four (37.5%) women had cuff
      salpingostomy, 16 (25%) had peritubal adhesiolysis, 12 (18.8%) had linear
      salpingostomy while 10 (15.6%) had tubo-cornual anastomosis. The most frequently
      used suture for tuboplasty was chromicised catgut No 2/0 which was used in 46
      (71.9%) of the women. Twenty-five (39.1%) women were followed up for more than 6
      months while the rest were lost to follow-up after 6 months. Three of the 25
      women followed-up for more than 6 months became pregnant giving a pregnancy rate
      of 12.0% for this sub-group and an overall pregnancy rate of 3/64 or 4.7%.
      CONCLUSIONS: Tubal surgery as seen at the University of Nigeria Teaching Hospital
      Enugu has a low pregnancy rate similar to ones reported from other Nigerian
      centres. If attention is paid to the currently recommended microsurgical
      techniques, the pregnancy rates following tubal surgery are likely to be better
      than has been documented in this study.

PMID- 16986290
TI  - An assessment of high risk sexual behaviour and HIV transmission among migrant
      oil workers in the Niger Delta area of Nigeria.
AB  - BACKGROUND: A cross--sectional behavioural survey undertaken amongst migrant oil
      workers of an oil exploration outfit operating in the Niger-Delta of Nigeria with
      the aim of assessing the interplay of migrancy, high-risk sexual behaviour and
      HIV transmission. METHOD: A total of 300 randomly selected migrant oil workers
      were assessed using structured questionnaires to evaluate key high - risk sexual
      behavioral parameters such as multiplicity of sexual partners, bisexuality
      (closet homosexuality), high grade sexual behaviour and lesbianism. Sampling
      period was two months with a control cohort of 200. RESULT: The prevalence of
      high risk sexual behaviour (HRSB) amongst the migrant oil workers was found to be
      7.7% while low-risk sexual behaviour (LRSB) was 92.3%. There was no record of
      HRSB in the control group. We did not also encounter any lesbian sexual
      orientation in this study. The distribution of HRSB amongst the migrant oil
      workers showed that the commonest variety was bisexuality (closet homosexuality)
      with 10(43.5%) followed by high-risk sexual behaviour 7(30.4%), while the least
      common was multiplicity of sexual partners with 6 (26.1%). Furthermore, majority
      of these individuals 19 (82.6%) were above the age of 35 years. The index of
      condom-use and acceptance was high. Here 14 (60.9%) found condom-use convenient
      while 13 (56.5%) regularly used the condom. CONCLUSION: This study confirms the
      existence of HRSB among migrant oil workers in the Niger delta. It is therefore
      advisable to focus interventionist and prevention programmes on this group which
      appear to be pivotal in the transmission and spread of HIV/AIDS in this
      environment.

PMID- 16986291
TI  - Acute appendicitis in Olabisi Onabanjo University Teaching Hospital Sagamu, a
      three year review.
AB  - BACKGROUND: Olabisi Onabanjo University Teaching Hospital is located in Sagamu, a
      suburban town with a population of 50,000 (1992 census). The hospital is a
      tertiary care facility in competition with a large number of private hospitals
      with different levels of competence. OBJECTIVE: The objective of the study is to
      review the outcome of the surgical management of acute appendicitis in our
      hospital. METHOD: A retrospective study of subjects who had appendectomy for the
      clinical diagnosis of acute appendicitis between January 2002 and December 2004
      was done. RESULT: 113 subjects consisting of 52 females (46%), and 61 males (54%)
      were studied. The mean age was 24.1 years, 71 subjects (62.9%) were in the 10-30
      years range. 57.5% of the subjects were students and 71 subjects (62.8) resided
      in urban area. All the subjects, had generalized in 23.9%). The mean duration of
      symptoms was 3.53 days with standard deviation of 3.69 days. Only 3 subjects
      presented on the day of onset of symptoms. Only 15 subjects (13.3%) had surgery
      on the day of admission. 69subjects (61.1%) had uncomplicated inflamed appendix
      at surgery and 2 subjects (1.8%) had clinically normal appendix. The mean
      duration of hospital stay was 10.6 days with standard deviation of 7.4. The
      commonest postoperative complication was pyrexia in 16 subjects (14.2%), followed
      by wound infection in 12 subjects (10.6%). One subject died (0.9%). CONCLUSION:
      The outcome reflects the late presentation and delay in surgical treatment.

PMID- 16986292
TI  - Barriers to timely initiation of breastfeeding among mothers of healthy full-term
      babies who deliver at the University of Port Harcourt Teaching Hospital.
AB  - OBJECTIVES: (I) To determine the barriers to timely initiation of breastfeeding
      in mothers who Hospital. (2). To determine if there is any statistical
      association between the time of initiation of breastfeeding and certain socio
      demographic, obstetric, psychosocial and environmental factors in the mother-baby
      pairs. METHODOLOGICAL: A prospective, hospital-based study of 500 consecutive
      health mother-infant pairs delivered at UPTH (both vaginally and by Caesarian
      section). Information was obtained using a structured questionnaire, medical
      record review and direct observation. Early initiation, i.e. mothers who
      initiated breastfeeding within 30 minutes of delivery (in the case of the
      vaginally delivered (VD) mothers) or within 30 minutes of recovery of post
      operative consciousness (in the case of those delivered by Caesarian section)
      were compared with those who initiated breastfeeding after 30 minutes (Late
      initiator) in the VD and C/S groups. The association between time of
      breastfeeding initiation and factors under consideration were determine using the
      chi-squared test. RESULTS: Approximately 34% of the VD mother initiated
      breastfeeding early while no mother with Caesarean section had early initiation
      of breastfeeding. The mean time of breastfeeding initiation was 3.35 -/+ 2.6
      hours in mother who had vaginal delivery, 6.50 +/- 3.4 hours and 5.9 +/- 1.9
      hours in those who had Caesarean section with general or spinal anaesthesia
      respectively. Among those with vaginal delivery, mothers younger than 25 years
      and of high socioeconomic class were found to practice early breastfeeding
      initiation. Delay in the time of repair of episiotomy and labour duration less
      than 12 hours were associated with early breastfeeding initiation. Early contact
      between baby and mother, help received on the delivery table and the presence of
      more than one delivery assistant also positively influenced breastfeeding
      initiation. Similarly, the presence of a breastfeeding-trained delivery assistant
      enhanced the mother' practice of early initiation of breastfeeding. Observation
      of routine labour ward practices such as cleaning of the newborn and
      weight/length measurement had negative impact on the practice of early initiation
      of breastfeeding. Early contact between the mother and her newborn on the
      delivery table with assistance to initate breastfeeding was the most important
      predictor of early breastfeeding initiation. Parity, attendance at the antenatal
      clinic, receipt of breastfeeding information and use of analgesics during labour
      did not show any statistical association with time of initiation of
      breastfeeding. CONCLUSION/RECOMMENDATION: There was a low prevalence of early
      initiation of breastfeeding in mothers delivered at the University of Port
      Harcourt Teaching Hospital. This low prevalence was due to delay in helping the
      newly delivered mother, especially those with Caesarean delivery. Routine labour
      ward practices interfere with the time of breastfeeding initiation. Routine
      labour ward and delivery table, specific assignment to the staff in the
      delivery/labour rooms help newly delivered mothers initiate breastfeeding early,
      and empowering the to request for babies are recommended.

PMID- 16986293
TI  - The relevance of VDRL as routine test in pregnant women: a critcal study.
AB  - AIM: To critically determine the relevance of Venereal Diseases Research
      Laboratories (VDRL) investigation as a routine serological screening for syphilis
      among pregnant women who receive antenatal care at the University of Nigeria
      Teaching Hospital (UNTH). METHODS: A retrospective chart review of result of
      serological test for syphilis among pregnant women during a five year period (1st
      January, 1997 to 31st December 2001) was undertaken. RESULTS: A total of 7469
      women booked. 7175 had routine serological test. 294 of the booked women failed
      to submit themselves for screening. The prevalence rate of syphilis in this study
      was 0.125%. VDRL seroreactivity had in previous studies in this center declined
      from 3.06% to 1.30%. It further declined to 0.98% in this study. CONCLUSION: The
      results strongly show a continuing very low prevalence rate of syphilis in Enugu.
      Nevertheless, we support continued screening of pregnant women inspite of this
      low prevalence rate, since this will eradicated the effects of undiagnosed and
      untreated syphilis.

PMID- 16986294
TI  - Tuberculosis and the eye.
AB  - OBJECTIVES: 1. To refresh knowledge on the epidemiology, pathogenesis, clinical
      features, investigations and treatment of ocular tuberculosis; 2. To highlight
      the ocular complication of tuberculosis. METHOD: Through an internet search and
      review of current literature on tuberculosis and its ocular complications, the
      information relevant to the objectives was obtained. CONCLUSIONS: TB can affect
      any structure in the eye and adnexae. Ocular TB is not easy to diagnose because
      most times there is no concurrent active systemic tuberculosis. However, once TB
      is confirmed, treatment is generally the same as for systemic TB. Topical
      steroids are given in addition, in cases like phlyctenulosis. Early diagnosis and
      treatment of ocular TB can prevent blindness or severe ocular morbidity. With the
      growing epidemic of HIV and the consequent increased risk of developing TB,
      ophthalmologist and eye care workers are, therefore, advised to heighten their
      suspicion of ocular TB.

PMID- 16986295
TI  - Tube thoracostomy in the management of pleural fluid collections.
AB  - OBJECTIVE: To determine the demographic pattern, indications and complications
      associated with tube thoracostomy in Nnamdi Azikiwe University Teaching Hospital
      (NAUTH) Nnewi. PATIENTS AND METHODS: A 5-year review of case records of patients
      who underwent tube thoracostomy at NAUTH Nnewi between January 1999 and December
      2003. Demographic data, clinical features, duration of drainage, complications
      and outcomes were analyzed. RESULTS: A total of 65 cases were studied, male:
      female ratio was 2.4:1. Eighteen patients (27.7%) were below 10 years of age.
      Infective cases accounted for 63.1% (41) of the cases that had tube thoracostomy.
      Forty-one patients (63.1%) had tube drainage for 10 days or less. Complication
      rate was 41.5% (27), mostly mild, with dislodgement of the tube accounting for
      about half. Failure rate of 13.7% (9) was recorded for the procedure. A mortality
      of 6.2% (4) was recorded but there was no procedure related death. Seven patients
      (10.8%) required further surgery. CONCLUSION: Tube thoracostomy is a simple and
      efficacious procedure for the treatment of pleural space collections. The safety
      of the procedure can be improved upon by adequate training in the insertion
      procedure, while proper selection of cases will reduce failure rate and
      unnecessary morbidity. Early resort to thoracoscopic or open surgery when tube
      thoracostomy is considered inappropriate or has failed will improve the success
      rate in the overall management of pleural fluid collections.

PMID- 16986296
TI  - Splenectomy in a rural surgical practice.
AB  - We reviewed the clinical presentation and indications for splenectomy in a rural
      community in Southern Nigeria from January 1988 - December, 2000, a period of 12
      years. A total of 17 cases were seen. Twelve (70.6%) were for big spleens due to
      sickle-cell anaemia, tropical splenomegaly syndrome, malignancy and 5 (29.4%)
      were due to trauma from road traffic injuries. Anaemia was a common feature in
      all the cases. Patients were followed up for 18 months but all those suspected to
      have malignancies died within eight months of surgery. Diseased spleen is
      commonly seen in rural community, its management in the face of limited
      facilities could be tasking, but some modicum of treatment has to be offered
      those who may not be able to honour a referral. It is the surgical treatment thus
      offered that is being shared in this review.

PMID- 16986297
TI  - Duodeno-pleural fistula: a rare complication of peptic ulcer perforation.
AB  - Duodenopleural fistula is a very uncommon complication of peptic ulcer
      perforation and usually follows empyema after a subdiaphragmatic abscess rupture.
      We present a rare case of duodenopleural fistula following subdiaphragmatic
      abscess, which resulted in thoracic empyema after gastric perforation.

PMID- 16986298
TI  - Chemo-radiation in advanced nasopharyngeal carcinoma, disease free after 6 years-
      a case report.
AB  - This is a case report of a patient with advanced nasopharyngeal Carcinoma, (T4 N2
      MO) who had chemo-radiation with Cisplatin based chemotherapy and total midplane
      dose of 60 Gray external beam radiation. Six years after treatment patient has
      remained disease free and the primary site histologically confirmed disease free
      with no clinical evidence of regional or distance metastases

PMID- 16986299
TI  - Appendico-vesicostomy in tile management of complex vesico-vaginal fistulae.
AB  - Complex vesico-vaginal fistulae (VVFs) continue to complicated prolonged
      obstructed labour in this country. Recently a young lady presented to us with a
      huge VVF, associated with loss of the urethra and bladder neck, severe
      gynaetresia and recto-vaginal fistula. Her VVF was successfully managed by an
      appendico-vesiscostomy.

PMID- 16986300
TI  - A smoldering/indolent myeloma with extensive abdominal presentation--case report.
AB  - A case of indolent/smoldering myeloma in a 70-year-old man is reported. He
      presented with an unusual multiple symptomatic myeloma with extramedulary
      impairment and absence of bone pain. He was treated with pulses of high-dose
      dexamethasone with commendable clinical improvement.

PMID- 16986301
TI  - Looking back to the future.

PMID- 16986302
TI  - The impact of the popular media on cosmetic dentistry.
AB  - The popular media's influence on social norms with respect to people's appearance
      is likely to have played a part in the recent growth of cosmetic dentistry. AIMS:
      This study was designed to investigate the manner in which the popular media have
      affected the perception and delivery of aesthetic dentistry in New Zealand.
      METHODS: A nationwide survey was posted to a random sample of 600 general dental
      practitioners (GDPs) requesting sociodemographic details and information on the
      types of aesthetic dental procedures provided and the demand for those.
      Information was also sought on GDPs' awareness of television programmes and
      reality "makeover" television shows (such as "Extreme Makeover") covering issues
      related to aesthetic dentistry, together with the impact of such programmes (and
      that of different print media) on their patients' perceptions of, and demand for,
      aesthetic dentistry. RESULTS: The response rate was 81.2 percent. A majority of
      participants perceived an increased demand for tooth whitening (77.8 percent) and
      veneers (54.8 percent) subsequent to the airing of those television programmes,
      with 85.2 percent reporting patients mentioning "Extreme Makeover" in relation to
      aesthetic dentistry. Some 56.8 percent believed that patients had higher
      aesthetic expectations subsequent to the airing of that programme. An increased
      demand for tooth whitening was reported by more female than male GDPs, and also
      by younger practitioners and those who were practising in larger centres. Similar
      patterns were observed with respect to GDPs recommending tooth whitening for
      patients. Women's magazines were ranked by GDPs as having the highest impact on
      patients' perceptions of aesthetic dentistry. CONCLUSION: The popular media
      (especially television) appear to have had an impact on the demand for various
      aesthetic dental procedures in New Zealand.

PMID- 16986303
TI  - Learning in oral biology: a comparison between deep and surface approaches.
AB  - It has been suggested that students approach their learning in at least two
      qualitatively different ways. In the surface approach, students see tasks as
      being imposed, for which they develop coping strategies focused on reproduction
      of essentials and memorising information for assessment rather than for
      understanding. In the deep approach, students seek to understand ideas to allow
      them to relate and integrate knowledge from other parts of their study and
      thereby develop conceptual frameworks from which they can derive solutions to
      novel problems. To these two approaches, a third, achieving approach, is often
      added, in which students aim to obtain the highest grades, whether or not they
      grasp the learning material. In this study we used a subject-specified version of
      Biggs' Study Process Questionnaire to obtain data about the way dental and dental
      technology students perceived and approached their learning in oral biology.
      Questionnaires were distributed to 62 second-year dental students and 23 second
      year dental technology students. Within each group the dependent variables
      examined were deep, surface or achieving approaches to learning. Analysis of
      these data showed that significant differences between dental and dental
      technology students centred on their approaches to learning. However, there were
      no significant differences attributable to gender, country of origin or
      ethnicity. While dental students, who had a relatively well developed
      understanding of the nature of their studies in oral biology at the start of
      their course, adopted deep learning strategies, dental technology students, who
      had had no prior experience of university education per se, were significantly
      more surface-orientated.

PMID- 16986304
TI  - Antibiotic prophylaxis for endocarditis.

PMID- 16986305
TI  - 12th BTK meeting: 'Systems Biology: redefining BioThermoKinetics'.

PMID- 16986306
TI  - Summation theorems for flux and concentration control coefficients of dynamic
      systems.
AB  - Metabolic control analysis (MCA) was developed to quantify how system variables
      are affected by parameter variations in a system. In addition, MCA can express
      the global properties of a system in terms of the individual catalytic steps,
      using connectivity and summation theorems to link the control coefficients to the
      elasticity coefficients. MCA was originally developed for steady-state analysis
      and not all summation theorems have been derived for dynamic systems. A method to
      determine time-dependent flux and concentration control coefficients for dynamic
      systems by expressing the time domain as a function of percentage progression
      through any arbitrary fixed interval of time is reported. Time-dependent flux and
      concentration control coefficients of dynamic systems, provided that they are
      evaluated in this novel way, obey the same summation theorems as steady-state
      flux and concentration control coefficients, respectively.

PMID- 16986307
TI  - Time-dependent hierarchical regulation analysis: deciphering cellular adaptation.
AB  - Cells adapt to changes in their environment by the concerted action of many
      different regulatory mechanisms. Examples of such mechanisms are feedback
      inhibition by intermediates of metabolism, covalent modification of enzymes and
      changes in the abundance of mRNAs and proteins. These mechanisms act in parallel
      at different levels in the cellular hierarchy while regulating a single process.
      Existing hierarchical regulation analysis determines the relative importance of
      these mechanisms when the cell regulates a transition from one steady-state to
      another. Here, the analysis is extended to the regulation of time-dependent
      phenomena, for which two methods are introduced and illustrated with a kinetic
      model incorporating transcription and translation of metabolic enzymes.

PMID- 16986308
TI  - Metabolic control analysis for large changes: extension to variable elasticity
      coefficients.
AB  - Modular approaches are powerful systems biology strategies to deal with
      complexity. They consist in lumping conceptually all that is irrelevant to the
      problem under study, leaving explicit the portions of interest. Modular (or top
      down) metabolic control analysis is a theoretical and experimental approach to
      study the sensitivity properties of complex metabolic systems. Initially, it was
      conceived for infinitesimal changes but, recently, it started to be developed for
      large metabolic changes. A central result of this approach is that the systemic
      properties, represented by control coefficients, can be expressed as a function
      of the properties of isolated modules, the elasticity coefficients. Here we
      extend the theory for large changes to the case that the elasticity coefficients
      depend on the extent of the change. The novel theory is used to analyse
      experimental data related to the control of glycolytic flux in Escherichia coli.
      Our analysis shows that the pattern of control for large changes is
      quantitatively and qualitatively different from the one obtained applying the
      infinitesimal treatment.

PMID- 16986309
TI  - Conditions for effective allosteric feedforward and feedback in metabolic
      pathways.
AB  - Whether an allosteric feedback or feedforward modifier actually has an effect on
      the steady-state properties of a metabolic pathway depends not only on the
      allosteric modifier effect itself, but also on the control properties of the
      affected allosteric enzyme in the pathway of which it is part. Different
      modification mechanisms are analysed: mixed inhibition, allosteric inhibition and
      activation of the reversible Monod-Wyman-Changeux and reversible Hill models. In
      conclusion, it is shown that, whereas a modifier effect on substrate and product
      binding (specific effects) can be an effective negative feedback mechanism, it is
      much less effective as a positive feedforward mechanism. The prediction is that
      catalytic effects that change the apparent limiting velocity would be more
      effective in feedforward activation.

PMID- 16986310
TI  - How to keep glycolytic metabolite concentrations constant when ATP/ADP and
      NADH/NAD+ change.
AB  - Glycolytic flux may increase over 100 times in skeletal muscle during rest-to
      work transition, whereas glycolytic metabolite concentrations remain relatively
      constant. This constancy cannot be explained by an identical direct activation of
      all glycolytic enzymes because the concentrations of ATP, ADP, AMP, P(i), NADH
      and NAD+, modulators of the activity of different glycolytic enzymes, change. It
      is demonstrated in the present in silico study that a perfect homeostasis of
      glycolytic metabolite concentrations can be achieved if glycolysis is divided
      into appropriate blocks of enzymes that are directly activated to a different
      extent in order to compensate the effect of the modulators.

PMID- 16986311
TI  - Comparing the regulatory behaviour of two cooperative, reversible enzyme
      mechanisms.
AB  - It is shown that both the reversible Hill equation and a generalised, reversible
      Monod-Wyman-Changeux equation can give analogous regulatory behaviour when
      embedded in a model metabolic pathway.

PMID- 16986312
TI  - Evaluation of a simplified generic bi-substrate rate equation for computational
      systems biology.
AB  - The evaluation of a generic simplified bi-substrate enzyme kinetic equation,
      whose derivation is based on the assumption of equilibrium binding of substrates
      and products in random order, is described. This equation is much simpler than
      the mechanistic (ordered and ping-pong) models, in that it contains fewer
      parameters (that is, no K(i) values for the substrates and products). The generic
      equation fits data from both the ordered and the ping-pong models well over a
      wide range of substrate and product concentrations. In the cases where the fit is
      not perfect, an improved fit can be obtained by considering the rate equation for
      only a single set of product concentrations. Due to its relative simplicity in
      comparison to the mechanistic models, this equation will be useful for modelling
      bi-substrate reactions in computational systems biology.

PMID- 16986313
TI  - Experimental evidence for allosteric modifier saturation as predicted by the bi
      substrate Hill equation.
AB  - The cooperative enzyme reaction rates predicted by the bi-substrate Hill equation
      and the bi-substrate Monod-Wyman-Changeux (MWC) equation when allosterically
      inhibited are compared in silico. Theoretically, the Hill equation predicts that
      when the maximum inhibitory effect at a certain substrate condition has been
      reached, an increase in allosteric inhibitor concentration will have no effect on
      reaction rate, that is the Hill equation shows allosteric inhibitor saturation.
      This saturating inhibitory effect is not present in the MWC equation.
      Experimental in vitro data for pyruvate kinase, a bi-substrate cooperative enzyme
      that is allosterically inhibited, are presented. This enzyme also shows inhibitor
      saturation, and therefore serves as experimental evidence that the bi-substrate
      Hill equation predicts more realistic allosteric inhibitor behaviour than the bi
      substrate MWC equation.

PMID- 16986314
TI  - Control analysis of the importance of phosphoglycerate enolase for metabolic
      fluxes in Lactococcus lactis subsp. lactis IL1403.
AB  - The glycolytic enzyme phosphoglycerate enolase (PGE) catalyses the step from 2
      phosphoglycerate to phosphoenolpyruvate in glycolysis. A control analysis of PGE
      on growth, glycolytic flux and product formation in Lactococcus lactis subsp.
      lactis IL1403 is presented. A library of strains with a modulated expression of
      PGE from 36 to 232% relative to wildtype level was constructed. Selected strains
      were studied with respect to growth, glycolytic flux and product formation in a
      chemically defined medium. On the basis of these data, flux control coefficients
      of PGE on the respective fluxes were calculated. At wildtype level, PGE was found
      to have no significant flux control on growth, glycolytic flux or product
      formation, but at 36% of PGE activity relative to wildtype, the flux control on
      the growth rate was estimated to be C(PGE)J(micro) approximately equal to 0.7, on
      the glycolytic flux C(PGE)J(g) approximately equal to 0.8, on lactate formation
      C(PGE)J(lactate) approximately equal to 1.3, on formate formation
      C(PGE)J(formate) approximately equal to 0.5 and on acetate formation C(PGE)
      J(acetate) approximately equal to 0.25. These flux control coefficients show that
      the metabolism of L. lactis subsp. lactis IL1403 becomes slightly more mixed acid
      at reduced PGE activities. Estimation of the relative turnover of PGE indicates
      that excess capacity of PGE in L. lactis IL1403 may be as low as twofold.

PMID- 16986316
TI  - Evolutionary changes of metabolic networks and their biosynthetic capacities.
AB  - The metabolic networks of different species show a large variety in their
      structural design. In this work, the evolution of functional properties of
      metabolism in relation with metabolic network structure is investigated. The
      metabolism of ancestral species is inferred from the metabolism of contemporary
      species using a Bayesian network model for metabolism evolution. Subsequently,
      these networks are analysed with the recently developed method of network
      expansion. This method allows for a structural analysis of metabolic networks as
      well as a quantification of network functions in terms of their synthesising
      capacities when they are provided with certain external resources. The
      evolutionary dynamics of one particular network function: the metabolic expansion
      of glucose is investigated.

PMID- 16986315
TI  - Contribution of ATP synthase to stimulation of respiration by Ca2+ in heart
      mitochondria.
AB  - A variety of experimental conditions were applied with the aim to estimate the
      correlation between the contribution of ATP synthase to the respiratory flux
      control and the calcium-induced activation of succinate oxidation in heart
      mitochondria isolated from rat, rabbit and guinea pig. The sensitivity of
      respiration in heart mitochondria to the decrease in temperature from 37 degrees
      C to 28 degrees C decreases in the order rabbit > guinea pig > rat. Ca2+ effect
      on succinate oxidation rate in state 3 respiration was species- and temperature
      dependent and ranged from 0 (rat, 37 degrees C) to +44% (rabbit, 28 degrees C).
      For mitochondria from all experimental animals, the increase of Ca2+ in
      physiological range of concentration did not change state 2 respiration rate, and
      the stimulatory effect of Ca2+ on state 3 respiration was more pronounced at 28
      degrees C than at 37 degrees C. The respiratory subsystem was sensitive to Ca2+
      ions only in rabbit heart mitochondria. A high positive correlation between Ca2+
      ability to stimulate succinate oxidation in state 3 and the control exerted by
      ATP synthase over the respiratory flux provides argument confirming stimulation
      of ATP synthase by Ca2+ ions.

PMID- 16986317
TI  - Hierarchy of metabolic compounds based on their synthesising capacity.
AB  - The concept of scopes is applied to analyse large metabolic networks. Scopes are
      defined as sets of metabolites that can be synthesised by a metabolic network
      when it is provided with given seeds (Sets of initial metabolic compounds). Thus,
      scopes represent synthesising capacities of the seeds in the network. A hierarchy
      is discussed in the sense that compounds, which are part of the scope of another
      compound, possess scopes themselves that are subsets of the former scope. This
      hierarchy is analysed by means of a directed acyclic graph. Using a simple
      chemical model, it is found that this hierarchy contains specific structures that
      can, to a large extent, be explained by the chemical composition of the
      participating compounds. In this way, it represents a new kind of map of
      metabolic networks, arranging the metabolic compounds according to their chemical
      capacity.

PMID- 16986318
TI  - Expansion of signal transduction networks.
AB  - Signal transduction networks of different cell types show a large variety in
      their structural design. In this paper, basic structural properties of signal
      transduction networks are investigated. For this, such networks with the recently
      developed method of network expansion are analysed. This method allows for a
      structural analysis of networks by calculating signal expansion profiles when
      provided with certain compounds, for example growth factors, inactive kinases and
      so on (seed compounds), to initiate such an expansion. The presented results may
      put forth valuable hints on the evolution of signalling networks.

PMID- 16986319
TI  - Pathway classification of TCA cycle.
AB  - The structural analysis of large metabolic networks exhibits a combinatorial
      explosion of elementary modes. A new method of classification has been developed
      [called aggregation around common motif (ACoM)], which groups elementary modes
      into classes with similar substructures. This method is applied to the
      tricarboxylic acid cycle and metabolite carriers. The analysis of this network
      evidences a great number of elementary flux modes (204) despite the low number of
      reactions (23). The ACoM is used to class these elementary modes in a low number
      of sets (8) with biological meanings.

PMID- 16986320
TI  - Connectivity matrix method for analyses of biological networks and its
      application to atom-level analysis of a model network of carbohydrate metabolism.
AB  - An approach for analysis of biological networks is proposed. In this approach,
      named the connectivity matrix (CM) method, all the connectivities of interest are
      expressed in a matrix. Then, a variety of analyses are performed on GNU Octave or
      Matlab. Each node in the network is expressed as a row vector or numeral that
      carries information defining or characterising the node itself. Information about
      connectivity itself is also expressed as a row vector or numeral. Thus,
      connection of node n1 to node n2 through edge e is expressed as [n1, n2, e], a
      row vector formed by the combination of three row vectors or numerals, where n1,
      n2 and e indicate two different nodes and one connectivity, respectively. All the
      connectivities in any given network are expressed as a matrix, CM, each row of
      which corresponds to one connectivity. Using this CM method, intermetabolite atom
      level connectivity is investigated in a model metabolic network composed of the
      reactions for glycolysis, oxidative decarboxylation of pyruvate, citric acid
      cycle, pentose phosphate pathway and gluconeogenesis.

PMID- 16986321
TI  - ScrumPy: metabolic modelling with Python.
AB  - ScrumPy is a software package used for the definition and analysis of metabolic
      models. It is written using the Python programming language that is also used as
      a user interface. ScrumPy has features for both kinetic and structural modelling,
      but the emphasis is on structural modelling and those features of most relevance
      to analysis of large (genome-scale) models. The aim is at describing ScrumPy's
      functionality to readers with some knowledge of metabolic modelling, but
      implementation, programming and other computational details are omitted. ScrumPy
      is released under the Gnu Public Licence, and available for download from
      http://mudshark.brookes.ac.uk/ ScrumPy.

PMID- 16986322
TI  - Challenges to be faced in the reconstruction of metabolic networks from public
      databases.
AB  - In the post-genomic era, the biochemical information for individual compounds,
      enzymes, reactions to be found within named organisms has become readily
      available. The well-known KEGG and BioCyc databases provide a comprehensive
      catalogue for this information and have thereby substantially aided the
      scientific community. Using these databases, the complement of enzymes present in
      a given organism can be determined and, in principle, used to reconstruct the
      metabolic network. However, such reconstructed networks contain numerous
      properties contradicting biological expectation. The metabolic networks for a
      number of organisms are reconstructed from KEGG and BioCyc databases, and
      features of these networks are related to properties of their originating
      database.

PMID- 16986323
TI  - Software tools that facilitate kinetic modelling with large data sets: an example
      using growth modelling in sugarcane.
AB  - A solution to manage cumbersome data sets associated with large modelling
      projects is described. A kinetic model of sucrose accumulation in sugarcane is
      used to predict changes in sucrose metabolism with sugarcane internode maturity.
      This results in large amounts of output data to be analysed. Growth is simulated
      by reassigning maximal activity values, specific to each internode of the
      sugarcane plant, to parameter attributes of a model object. From a programming
      perspective, only one model definition file is required for the simulation
      software used; however, the amount of input data increases with each extra
      interrnode that is modelled, and likewise the amount of output data that is
      generated also increases. To store, manipulate and analyse these data, the
      modelling was performed from within a spreadsheet. This was made possible by the
      scripting language Python and the modelling software PySCeS through an embedded
      Python interpreter available in the Gnumeric spreadsheet program.

PMID- 16986324
TI  - Molecular modelling of K(ATP) channel blockers-ADP/ ATP carrier interactions.
AB  - The modelling of molecule-molecule interactions has been widely accepted as a
      tool for drug discovery and development studies. However, this powerful technique
      is unappreciated in physiological and biochemical studies, where it could be
      extremely useful for understanding the mechanisms of action of various compounds
      in cases when experimental data are controversial due to complexity of the
      investigated systems. In this study, based on the biochemical data suggesting
      involvement of mitochondrial ADP/ATP carrier in K+ and H+ transport to
      mitochondrial matrix molecular modelling is applied to elucidate the possible
      interactions between the ADP/ATP carrier and its putative ligands--K(ATP) channel
      blockers glybenclamide, tolbutamide and 5-hydroxydecanoate. Results revealed that
      K(ATP) channel blockers could bind to the specific location proximal to H1, H4,
      H5 and H6 transmembrane helices within the cavity of the ADP/ ATP carrier.
      Analysis of the predicted binding site suggests that K(ATP) channel blockers
      could interfere with both the ADP/ATP translocation and possible cation flux
      through the ADP/ATP carrier, and supports the hypothesis that the ADP/ATP carrier
      is a target of K(ATP) channel modulators.

PMID- 16986325
TI  - Brownian dynamic model of the glycine receptor chloride channel: effect of the
      position of charged amino acids on ion membrane currents.
AB  - Glycine is the major inhibitory neurotransmitter in the brainstem and spinal
      cord, where it participates in a variety of motor and sensory functions. It
      activates a special type of ligand-gated membrane receptor, which provides for Cl
      ion conductance of the neuronal membrane. Computer simulations of a single
      channel current through this receptor have been carried out on the basis of
      Brownian (Langevin) dynamics. The dependence of the currents on pore diameter and
      the location of the charged amino acid residues have been obtained. It has been
      shown that the presence and the symmetry of the filter-forming residues
      determined not only the ion-selectivity of the channel but also increased
      transmembrane anion current.

PMID- 16986326
TI  - Is there an optimal ribosome concentration for maximal protein production?
AB  - A core model is presented for protein production in Escherichia coli to address
      the question whether there is an optimal ribosomal concentration for non-ribosome
      protein production. Analysing the steady-state solution of the model over a range
      of mRNA concentrations, indicates that such an optimum ribosomal content exists,
      and that the optimum shifts to higher ribosomal contents at higher specific
      growth rates.

PMID- 16986327
TI  - Organisation of B-cell receptors on the cell membrane.
AB  - B-cell receptors (BCRs) have been reported to organise into oligomeric clusters
      on the B-cell surface, and mutations, that are likely to interfere with such
      clustering, result in B-cell unresponsiveness. This has led to the suggestion
      that pre-formed BCR clusters may be crucial for B-cell signalling. However,
      neither the size nor the fraction of BCRs organised in such clusters have yet
      been determined in experiments. Hence, the authors use a statistical approach to
      predict the membrane organisation of BCRs, based on available experimental data.
      For physiological parameters, most BCRs will organise into supramolecular
      polymers that comprise about five receptors where the non-covalent interactions
      are mediated by the IgH transmembrane helix. A reduction in the density of IgM to
      2-5% of the normal density, a characteristic of anergic MD4 B cells, strongly
      reduces IgM polymerisation, and it is suggested that impaired BCR clustering may
      be responsible for the unresponsiveness of anergic B cells.

PMID- 16986328
TI  - Computational model of excitable cell indicates ATP free energy dynamics in
      response to calcium oscillations are undampened by cytosolic ATP buffers.
AB  - Mitochondria in excitable cells are recurrently exposed to pulsatile calcium
      gradients that activate cell function. Rapid calcium uptake by the mitochondria
      has previously been shown to cause uncoupling of oxidative phosphorylation. To
      test (i) if periodic nerve firing may cause oscillation of the cytosolic
      thermodynamic potential of ATP hydrolysis and (ii) if cytosolic adenylate (AK)
      and creatine kinase (CK) ATP buffering reactions dampen such oscillations, a
      lumped kinetic model of an excitable cell capturing major aspects of the
      physiology has been developed. Activation of ATP metabolism by low-frequency
      calcium pulses caused large oscillation of the cytosolic, but not mitochondrial
      ATP/ADP, ratio. This outcome was independent of net ATP synthesis or hydrolysis
      during mitochondrial calcium uptake. The AK/CK ATP buffering reactions dampened
      the amplitude and rate of cytosolic ATP/ADP changes on a timescale of seconds,
      but not milliseconds. These model predictions suggest that alternative sources of
      capacitance in neurons and striated muscles should be considered to protect ATP
      free energy-driven cell functions.

PMID- 16986329
TI  - California runs for coverage. Even though Schwarzenegger is likely to veto single
      payer bill, other states could start clamoring for similar access plans.
AB  - With little afoot in D.C. to ease the uninsured crisis, state initiatives are
      attempting to take up the slack. In California last week, supporters rallied for
      a universal coverage bill that Gov. Schwarzenegger is expected to veto. "States
      are looking at the federal government and seeing that nothing's happening," one
      observer says.

PMID- 16986330
TI  - 46.6 million and counting. But some question new census numbers.

PMID- 16986331
TI  - Out of the running. Healthcare is a back-burner issue this election year.

PMID- 16986332
TI  - More money for the cause. For-profit hospital lobby is solidly in the black.

PMID- 16986333
TI  - Pressure on for gain-sharing demos. Nov. 1 deadline fast approaching, CMS already
      one step behind.

PMID- 16986334
TI  - Sources say so far, so good ... but JCAHO's leadership chapter still needs a
      revise.

PMID- 16986335
TI  - Reprocessing hearings set.

PMID- 16986336
TI  - Running interference. Justice Department looks into S.C.'s CON specifics.

PMID- 16986337
TI  - No simple answers. Without political will for comprehensive change, access
      problem will worsen.

PMID- 16986338
TI  - Trade wars. While our annual group purchasing survey shows continued growth,
      organizations face ongoing battles involving government inquiries, vendor
      disputes.

PMID- 16986339
TI  - Meeting their obligations. New York merger ends in divorce, but there's still the
      matter of the family debt.

PMID- 16986340
TI  - 20 largest healthcare management consulting firms. Ranked by 2005 revenue from
      provider consulting fees.

PMID- 16986341
TI  - Competence in the field of aging within otorhinolaryngology and head-neck
      nursing.
AB  - ORL-Head and Neck Nursing proudly announces the launch of its new journal
      department, entitled "Gero-ORL." This guest editorial, written by the new
      Department's Editor, and two past presidents of SOHN, presents the history of
      SOHN's agenda on aging, provides the background and rationale for the Gero-ORL
      Department, and solicits manuscripts.

PMID- 16986342
TI  - An overview of current techniques for tonsillectomy.
AB  - Tonsillectomy remains a commonly performed surgical procedure. Although common,
      it has complications and associated morbidity. In an era of cost containment,
      indications for surgery have been promulgated by the American Academy of
      Otolaryngology-Head and Neck Surgery (2000) to aid the healthcare practitioner in
      appropriate referral to the surgeon, as well as clinical indicators to help
      insure that surgical intervention is in the best interest of the patient.
      Surgical techniques are constantly evolving, with the goal of reducing
      complications and improving postoperative recovery and healing. Review of the
      literature suggests that new technologies may or may not be better than the tried
      and-true surgical techniques combined with good post-operative nursing care.

PMID- 16986343
TI  - Mentoring future leaders: The Midwinter SOHN Board Meeting guest attendee
      program.
AB  - Leadership requires vision to fulfill one's mission or purpose. Leadership, in
      part, is the art of influencing others to achieve goals. Leaders often find
      creative solutions to achieve their goals and mobilize the resources needed for
      attainment (McArthur, 2006). The Society of Otorhinolaryngology and Head-Neck
      Nurses (SOHN) Board of Directors (BOD) and elected officers developed an
      innovative program to mentor future leaders by awarding two members-at-large the
      opportunity to attend a national SOHN BOD meeting. The goal of this mentoring
      program is to provide guidance, encouragement, and support for
      otorhinolaryngology nurses to assume future leadership roles within the
      organization (Andresen, 2006; Krouse, 2004). The purpose of this article is to
      share the author's perspectives after attending a national SOHN BOD meeting as a
      guest attendee.

PMID- 16986344
TI  - Patient Education. Sinusitis: Special considerations for aging patients.

PMID- 16986345
TI  - Social security: does it have a future?
AB  - Social Security has been available to Americans since 1937. The current
      administration is proposing a system overhaul to avoid a predicted bankruptcy by
      2017. Nurses are frequently asked to help patients understand benefits or to
      complete disability paperwork. Nurses can also influence future legislation. This
      article will review the current Social Security System and attempt to explain the
      proposed changes.

PMID- 16986346
TI  - Systemic treatment of breast cancer. Two decades of progress.
AB  - Over the past 20 years we have witnessed the emergence of a new generation of
      aromatase inhibitors as valuable antiestrogens in the management of both advanced
      and early-stage breast cancer. In addition, the list of cytotoxic
      chemotherapeutic agents useful in the control of breast cancer has grown
      considerably. The emergence ofanthracyclines was a major chemotherapeutic step
      forward in the 1980s, and the taxanes have clearly been the agents with the
      greatest impact on breast cancer treatment over the past decade. The end of the
      past 2 decades has been characterized by a greater understanding of the molecular
      biology of breast cancer, rational drug design, and the development of agents
      that disrupt specific cellular targets and pathways. The development of better
      prognostic and predictive assays that employ a panel of genes involved in the
      malignant and metastatic phenotype promises to allow clinicians to better select
      patients who could forgo adjuvant chemotherapy. Finally, adjunctive and
      supportive therapy of breast cancer has evolved substantially over the past 20
      years. This review will highlight some of the landmark accomplishments during
      this time, and offer a glimpse at where we might be 20 years from now.

PMID- 16986347
TI  - Managing early-stage breast cancer in your older patients.
AB  - As the aging population in the United States continues to grow, the incidence of
      diseases of the elderly, such as breast cancer, are increasing. Many more elderly
      women are expected to be diagnosed with new breast cancers, most of them in an
      early stage. Appropriate treatment of these women is important, as they have
      poorer outcomes when undertreated. In this review, we will discuss the biology
      and treatment of early breast cancer in elderly women. We will focus on the role
      of comorbidity and its effect on life expectancy, treatment decisions, current
      recommendations for primary treatment with surgery, radiation and neoadjuvant
      strategies, and adjuvant treatment including local radiation therapy and systemic
      treatment with endocrine therapy, chemotherapy, and newer agents. Finally we will
      discuss the importance of clinical trials in the elderly.

PMID- 16986348
TI  - Aromatase inhibitors and bone loss.
AB  - The aromatase inhibitors (AIs) anastrozole (Arimidex), letrozole (Femara), and
      exemestane (Aromasin) are significantly more effective than the selective
      estrogen-receptor modulator (SERM) tamoxifen in preventing recurrence in estrogen
      receptor-positive early breast cancer. Aromatase inhibitors are likely to replace
      SERMs as first-line adjuvant therapy for many patients. However, AIs are
      associated with significantly more osteoporotic fractures and greater bone
      mineral loss. As antiresorptive agents, oral and intravenous bisphosphonates such
      as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva),
      pamidronate (Aredia), and zoledronic acid (Zometa) have efficacy in preventing
      postmenopausal osteoporosis, cancer treatment-related bone loss, or skeletal
      complications of metastatic disease. Clinical practice guidelines recommend
      baseline and annual follow-up bone density monitoring for all patients initiating
      AI therapy. Bisphosphonate therapy should be prescribed for patients with
      osteoporosis (T score < -2.5) and considered on an individual basis for those
      with osteopenia (T score < -1). Modifiable lifestyle behaviors including adequate
      calcium and vitamin D intake, weight-bearing exercise, and smoking cessation
      should be addressed. Adverse events associated with bisphosphonates include
      gastrointestinal toxicity, renal toxicity, and osteonecrosis of the jaw. These
      safety concerns should be balanced with the potential of bisphosphonates to
      minimize or prevent the debilitating effects of AI-associated bone loss in
      patients with early, hormone receptor-positive breast cancer.

PMID- 16986349
TI  - Osteonecrosis of the jaw in cancer patients receiving IV bisphosphonates.
AB  - Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing
      frequency over the past few years. ONJ is most often identified in patients with
      cancer who are receiving intravenous bisphosphonate therapy but it has also been
      diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions.
      The condition involves exposed bone of the maxilla or mandible. Although it is
      often associated with a recent dental surgical procedure, spontaneous ONJ can
      also occur. Patients commonly present with symptoms. Through case reporting and
      clinical experience, there is a suggestion that the incidence of ONJ in patients
      with cancer receiving intravenous bisphosphonates ranges between 1% and 10%.
      Management of ONJ focuses on maximizing oral health, conservative actions with
      mouth rinses, antibiotics, and avoidance of unnecessary invasive dental
      procedures. The currently available data on ONJ are reviewed here.

PMID- 16986350
TI  - A woman with primary breast cancer and a solitary sternal metastasis.

PMID- 16986351
TI  - A STAR is born.

PMID- 16986352
TI  - The EBP controversy: misconception, misunderstanding, or myth.

PMID- 16986353
TI  - Adverse patient events and knowledge development needs.

PMID- 16986354
TI  - Pragmatic utility: using analytical questions to explore the concept of ethical
      sensitivity.
AB  - Ethical sensitivity is the means and capacity through which professionals strive
      to understand and compassionately respond to those in their care. As a
      transdisciplinary concept, ethical sensitivity can facilitate knowledge
      development across disciplines. To clarify and reduce ambiguities, the concept of
      ethical sensitivity was analyzed using the pragmatic utility method. With this
      method, the investigator uses analytical questions arising from in-depth
      understanding of the literature to synthesize data, to push beyond the limits of
      isolated findings and individual disciplines, to identify shared knowledge, and
      to provide new insights, lines of questioning, and direction. In this article,
      the role, technique, results, advantages, and limitations of the pragmatic
      utility method are elucidated. Characteristics of ethical sensitivity are its (a)
      preconditions of suffering and vulnerability cues, uncertainty, relationships
      characterized by receptivity and responsiveness, and courage; (b) attributes of
      moral perception, affectivity, and dividing loyalties; and (c) outcomes of client
      comfort and well-being, professional learning and self-transcendence, and
      integrity-preserving compromise. Use of the pragmatic utility method enhanced
      comprehension, meaning, relevance, and dimensions of the concept of ethical
      sensitivity as conveyed in the academic literature of selected professional
      disciplines.

PMID- 16986355
TI  - Pain assessment in the perspective of action science.
AB  - Pain assessment is examined in the perspective of action science with the aim to
      discover espoused theories and theories-in-use for pain assessment. In action
      science there are 2 sets of theories of action: espouse theories and theories-in
      use, which often exist in practice inconsistently with each other resulting in
      haphazard actions. Espoused theories of pain and pain assessment and a set of
      theories-in-use were revealed. Alignments between the espoused theories and the
      theories-in-use, and disparities between these theories were found in the pain
      assessment situations. The findings point to possible explanations regarding
      problems in pain assessment, and provide insights into our understanding of
      nursing practice especially in relation to pain assessment.

PMID- 16986356
TI  - Evaluating an Interpersonal Model of Depression among adults with Down syndrome.
AB  - The Interpersonal Model of Depression (IMD) based on the Theory of Human
      Relatedness (Hagerty, Lynch-Sauer, Patusky, & Bouwsema, 1993) is evaluated among
      adults with Down syndrome. One hundred subjects participated, with 32% having
      elevated depression scores and 40% stating they felt lonely. The relationship
      between depression, perceived social support, loneliness, and life satisfaction
      is statistically significant, F(6, 172) = 4.36, p < .001. Loneliness, social
      isolation, loss of sense of well-being, self-hate, and social withdrawal are
      important interpersonal manifestations and represent increasing levels of
      depression. Social and emotional loneliness are two dimensions of loneliness. The
      IMD provides a framework to assess depression in this population. Research on the
      efficacy of depression treatment based on the IMD is needed.

PMID- 16986357
TI  - Having a sibling with schizophrenia: a phenomenological study.
AB  - Limited attention has been paid to experiences of individuals with siblings
      diagnosed with schizophrenia. The purpose of this article is to address this gap
      by exploring the impact of having a brother or sister with schizophrenia. The
      lived experience of 6 individuals with a sibling with schizophrenia was explored
      using van Manen's (1997) Hermeneutic Phenomenology. Four themes were identified:
      struggling to understand, struggling with the system, caring for the sibling, and
      seeing beyond the illness. Health care providers need to re-evaluate current
      approaches for assisting individuals to cope with having a sibling with
      schizophrenia. Inclusion in the plan of care and recognition of their struggle is
      essential for individuals having a sibling with schizophrenia.

PMID- 16986358
TI  - Smoking history and prior surgical resection predict sensitivity to gefitinib in
      advanced non-small-cell lung cancer.
AB  - BACKGROUND: Gefitinib is an inhibitor of epidermal growth factor receptor
      tyrosine kinase, and induces radiographic regression and symptomatic improvement
      in patients with non-small cell lung cancer (NSCLC). Phase II trials suggested
      female sex and adenocarcinoma were associated with response, never smoking
      history and adenocarcinoma were associated with survival. We attempted to
      identify additional clinical features associated with response and survival.
      METHODS: We reviewed medical records and imaging studies of all 68 NSCLC patients
      treated by gefitinib monotherapy in our institution. We identified patients
      experiencing disease control and compared their clinical features with those of
      other patients. We considered partial response, stable disease or incomplete
      response and stable disease to be evidence of disease control. Univariate and
      multivariate analysis were performed to determine predictive and prognostic
      factors associated with disease control and survival. RESULTS: Of 68 patients, 20
      (29.4%) experienced disease control. Variables identified as significant for
      disease control with gefitinib included never smoking history (p=0.0128) and
      history of curative surgical resection (p=0.0007) on multivariate analysis.
      Variables identified as significant for overall survival included never smoking
      history (p=0.0128), history of curative surgical resection (p=0.0007), and
      performance status (PS) of 0 and 1 (p=0.0001) on multivariate analysis.
      CONCLUSIONS: Our findings suggest that never smoking history and history of
      curative surgical resection are key factors for disease control and prognostic
      factors in patients with NSCLC treated with gefitinib.

PMID- 16986359
TI  - Activation of mitogen-activated protein kinases, activator protein-1, and nuclear
      factor-kappaB during acute rejection after heterotopic heart transplantation in
      rats.
AB  - BACKGROUND: Activation of mitogen-activated protein kinases (MAPKs), including c
      Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs),
      and p38MAPK during acute cardiac rejection is not clear. This study aimed to
      determine whether MAPKs and transcriptional factors such as activator protein-1
      (AP-1) and nuclear factor-kappaB (NF-kappaB) were involved in acute rejection
      after cardiac transplantation. METHODS: Hearts from Lewis (LEW) rats (group C) or
      DA rats (group R) were transplanted into the abdomen of recipients (LEW). Grafts
      were collected at the 1st, 3rd, or 5th postoperative day (POD). ERKs were
      measured by Western blot analysis, and JNKs were measured by in-gel kinase assay.
      AP-1 and NF-kappaB DNA binding activities were determined using an
      electrophoretic mobility shift assay. We assessed functions of donor hearts using
      echocardiography. RESULTS: Heart rates and myocardial contraction significantly
      decreased at POD 5 in group R. Phosphorylated p42ERK and p44ERK in the left
      ventricular free wall (FW) and septal wall (SW) of group R significantly
      increased at POD 5 compared to those of group C at POD 1. Activities of p46JNK
      and p55JNK in the FW and SW of group R also significantly increased at POD 5. AP
      1 DNA binding activities in the FW and SW of group R significantly increased at
      POD 5, and NF-kappaB DNA binding activities of group R significantly increased at
      PODs 3 and 5. CONCLUSIONS: We conclude that ERK, JNK, AP-1, and NF-kappaB are
      activated during acute rejection. The MAPK pathways may play an important role in
      acute cardiac rejection.

PMID- 16986360
TI  - The application of the hemoglobin saturation sensor and indocyanine green (ICG)
      for blood flow measurement.
AB  - BACKGROUND: The aim in this study is to evaluate a new blood flow measurement
      applying a hemoglobin saturation sensor and indocyanine green (ICG) in circuit
      and animal models. METHODS: 1) In the basic study, the blood was mixed in a tube
      with ICG, and a near-infrared sensor was placed in this tube. The standard curve
      of the relationship between ICG concentration and optical density was obtained.
      2) In the circuit model, the blood was circulated by the roller pump. ICG was
      injected in this circuit and its concentration was calculated from the change in
      optical density at 810 nm. Rate of flow was calculated based on the Fick's
      principle. The validity of this method was evaluated by Bland and Altman
      analysis. 3) In the animal model, a hemoglobin saturation sensor was inserted
      into three anesthetized dogs via the jugular vein, and iced ICG was injected for
      calculating cardiac output. Cardiac output was calculated by the same theory of
      the circuit model. The validity of this method was also evaluated by Bland and
      Altman analysis. RESULTS: 1) A standard curve was drawn from 11 different points
      (r2=0.99). 2) The calculated flow rate correlated well with the actual flow rate
      (r2=0.97). 3) The calculated cardiac output correlated well with results obtained
      with the thermodilution method. CONCLUSIONS: Application of a hemoglobin
      saturation sensor and ICG to blood flow measurement was reliable and useful in
      both circuit and animal models. This method may be clinically useful for
      measurement of blood flow.

PMID- 16986361
TI  - Endothelin-converting enzyme expression in the neointima after percutaneous
      coronary intervention.
AB  - Smooth muscle cells (SMCs) are the major cellular component of neointimal tissues
      after percutaneous coronary intervension (PCI). Endothelin-1 (ET-1) is a powerful
      vasoconstrictor and has a mitogenic effect on SMCs. Endothelin-converting enzyme
      (ECE) is a key enzyme in the process of ET-1 generation. However, the expression
      of ECE in association with post-PCI repair processes has not been reported.
      Thirteen coronary sites after PCI obtained at autopsy and 6 atherectomy specimens
      obtained from restenotic sites were investigated. Frozen sections were stained
      with antibodies against ECE, SMCs, macrophages, and endothelial cells. The
      immunoreactivity of ECE was quantified using computer-aided planimetry. At the
      early stage after PCI, most neointimal SMCs expressed ECE. The ECE-positive cell
      area was significantly (p<0.005) larger in the sites within 3 months after PCI
      than in the sites from 6 months onward. In atherectomy specimens, neointimal SMCs
      showed distinct ECE positivity. These findings suggest that ECE is upregulated in
      the neointima at early stages after PCI injury. ECE may be one of the mediators
      in the repair processes after PCI in humans.

PMID- 16986362
TI  - Effects of different sampling points on evaluation of fetal descending aortic
      flow.
AB  - BACKGROUND: Widespread use of fetal aortic blood flow velocity measurements for
      assessment of fetal circulatory status has been precluded by difficulties in
      achieving an adequate Doppler insonation angle at particular sampling points. The
      goal of this study was to evaluate the differences in resistance index (RI) and
      systolic peak velocity (Vmax) of fetal aortic blood flow velocity waveforms
      throughout gestation among various Doppler sampling points. METHODS: A total of
      551 normal women between 18-41 weeks of pregnancy participated in this study.
      Pulsed Doppler flow velocity waveforms were acquired from three different aortic
      sampling points (thoracic portion, beneath the diaphragm, and abdominal portion)
      of the fetal descending aorta. The Vmax and RI were calculated at the respective
      sampling points. RESULTS: The Vmax were significantly lower in abdominal portion
      than those in thoracic portion at every time point (from 69 +/- 11 cm/second in
      thoracic to 49 +/- 8 cm/second in abdominal portion at 18-19 gestational weeks,
      p<0.0001), and RI were also lower (from 0.84 +/- 0.05 in thoracic portion to 0.76
      +/- 0.05 in abdominal portion at 18-19 gestational weeks, p<0.0001). Significant
      increase in the Vmax was seen until third trimester (from 58+/-10 cm/second at 18
      19 gestational weeks to 113 +/- 13 cm/second at 38-39 gestational weeks beneath
      the diaphragm, p<0.0001), while the RI remained stable (0.79 +/- 0.04 at 18-19
      gestational weeks; 0.80 +/- 0.05 at 38-39 gestational weeks beneath the
      diaphragm). CONCLUSIONS: In measuring the fetal circulatory status, these data
      demonstrate that the sampling point should be considered when evaluating the
      maximum systolic velocity and the resistance index of the fetal descending aorta.

PMID- 16986364
TI  - Long term care high on NAHC's 2006 legislative priorities.

PMID- 16986363
TI  - Surgical indications for spontaneous pneumothorax in patients over 50 years of
      age.
AB  - BACKGROUND: Surgery is often required in cases of spontaneous pneumothorax. This
      situation can pose considerable difficulty with correct preoperative estimate of
      pulmonary function. Simple indications for surgery are mandatory, especially in
      aged patients. METHODS: To examine the indications and safety of surgery in
      patients over 50 years, 23 operations in 22 patients over a 6-year period from
      1998 to 2003 were reviewed retrospectively. All 23 cases had a grade 2 or better
      performance status. In all cases, operations were performed with bullectomy or
      pneumonorrhaphy by a limited thoracotomy with videothoracoscopy in 5 cases.
      RESULTS: All patients recovered to the same performance status as before the
      onset of the pneumothoraces, with the exception of one who died, and changes
      between pre- and postoperative arterial oxygen or carbon dioxide tension were not
      significant. Lung-related postoperative complications, including 1 mortality
      (4%), occurred in three cases who required emergency operation because of massive
      air leaks with incomplete lung reexpansion, obvious mediastinal emphysema or
      severe subcutaneous emphysema. CONCLUSIONS: Surgical interventions may be safely
      performed when the patient's performance status is grade 2 or better, but care
      must be taken to avoid postoperative complications in preoperative conditions as
      massive air leaks with incomplete lung reexpansion, obvious mediastinal emphysema
      or severe subcutaneous emphysema.

PMID- 16986365
TI  - Implications for home care providers.

PMID- 16986366
TI  - Opportunities & challenges for long term care.

PMID- 16986367
TI  - Americans for long term care security.

PMID- 16986368
TI  - Funding home care with a reverse mortgage.

PMID- 16986369
TI  - The changing landscape of long term home health care in New York City and state.

PMID- 16986370
TI  - Fraud and abuse aspects to Medicare's new provider enrollment requirements.

PMID- 16986371
TI  - New requirements for establishing and maintaining Medicare participation.

PMID- 16986372
TI  - National EHR adoption: action steps.

PMID- 16986373
TI  - Senators Kennedy and DeWine introduce bipartisan bill for long term care: bill
      seeks to open doors of opportunity by helping individuals overcome barriers to
      independence.

PMID- 16986374
TI  - The "STATE" of home care & hospice.
AB  - This issue of CARING is focusing on the new dimensions in home care technology.
      As a group, the home care industry's trade associations have been in the
      vanguard, promoting technological advancements to their provider members. Many of
      our home care and hospice associations, including the National Association for
      Home Care & Hospice (NAHC), have made the idea of promoting the use of new
      technology, a strategic priority.

PMID- 16986375
TI  - MedPACs June 2006 report to the Congress: growth in Medicare expenditures and
      potential payment system refinements.

PMID- 16986376
TI  - Checking wind speed when on the brink and direction.

PMID- 16986377
TI  - The long term affordability of long term care: what are Congress' options?

PMID- 16986378
TI  - MedPAC was right.

PMID- 16986379
TI  - Planning your vacation...and your life!

PMID- 16986380
TI  - Top 10 considerations when contemplating the sale of a home health agency or
      hospice.

PMID- 16986381
TI  - Another mythical disease.

PMID- 16986382
TI  - Long term care: the last great civil rights battle.

PMID- 16986383
TI  - The current status of thromboprophylaxis after trauma: a story of confusion and
      uncertainty.
AB  - It is difficult to support a standard of care for venous thromboprophylaxis after
      trauma when there is no convincing research that any of the currently used
      methods is consistently effective. Because many conclusions from the nontrauma
      literature have been misleadingly extrapolated to trauma patients, this review
      focuses exclusively on trauma articles. These articles present variable results.
      The rates of deep venous thrombosis and pulmonary embolism are widely different
      even among similar trauma populations. The heparin-unfractionated or low
      molecular-weight and calf compression methods fail to show a reproducible effect
      in decreasing venous thromboembolic events. The current methods of venous
      thromboprophylaxis after trauma are inadequate and further research in this area
      is direly needed.

PMID- 16986384
TI  - Obesity alters rat abdominal flap survival.
AB  - Obesity presents a risk factor for flap-related complications in autologous
      tissue breast reconstruction. In this study, an animal model was developed to
      examine this phenomenon. Abdominal flaps based on a superficial inferior
      epigastric pedicle were elevated in an experimental group of obese Zucker (fa/fa)
      rats (n = 8; mean weight, 413 g) and in their lean littermates (n = 9; mean
      weight, 276 g). Flap tissue was harvested from a subset of both groups for
      baseline characterization, including histology, and assays for ATP and oxidative
      phosphorylation uncoupler, UCP-2. Flaps were then evaluated for survival by
      planimetry at 4 and 7 days postprocedure. Flap survival 7 days postoperatively
      was reduced in obese (42.0% +/- 8.6%) versus lean (70.3% +/- 6.7%) rats (P <
      0.05). At baseline, flap tissue of obese animals had decreased ATP content
      relative to lean counterparts (0.12 +/- 0.12 nM/microg vs 0.36 +/- 0.23 nM/microg
      protein, P < 0.05), whereas UCP2 mRNA was higher in obese flap tissue versus
      lean. Reduced viability of obese flaps may be attributable to decreased baseline
      energy stores due to oxidative phosphorylation uncoupling by UCP-2. This study is
      the first to introduce a promising animal model for examining the effect of
      obesity on increased flap-related complications in breast reconstruction using
      autologous tissue.

PMID- 16986385
TI  - Detection of cervical spine injuries in alert, asymptomatic geriatric blunt
      trauma patients: who benefits from radiologic imaging?
AB  - There are differing recommendations in the literature regarding cervical spine
      imaging in alert, asymptomatic geriatric patients. Previous studies also have not
      used computed tomography routinely. Given that cervical radiographs may miss up
      to 60 per cent of fractures, the incidence of cervical spine injuries in this
      population and its implications for clinical management are unclear. We conducted
      a retrospective study of blunt trauma patients 65 years and older who were alert,
      asymptomatic, hemodynamically stable, and had normal neurologic examinations. For
      inclusion, patients were required to have undergone computed tomography and plain
      radiographs. The presence and anatomic location of potentially distracting
      injuries or pain were recorded. Two hundred seventy-four patients were included,
      with a mean age of 76 +/- 10 years. The main mechanisms of injury were falls
      (51%) and motor vehicle crashes (41%). Nine of 274 (3%) patients had cervical
      spine injuries. The presence of potentially distracting injuries above the
      clavicles was associated with cervical injury when compared with patients with
      distracting injuries in other anatomic locations or no distracting injuries
      (8/115 vs 1/159, P = 0.03). There was no association of cervical spine injury
      with age greater or less than 75 years or with mechanism of injury. The overall
      incidence of cervical spine injury in the alert, asymptomatic geriatric
      population is low. The risk is increased with a potentially distracting injury
      above the clavicles. Patients with distracting injuries in other anatomic
      locations or no distracting injuries may not need routine cervical imaging.

PMID- 16986386
TI  - Results after laparoscopic fundoplication: does age matter?
AB  - Antireflux fundoplications are undertaken with hesitation in older patients
      because of presumed higher morbidity and poorer outcomes. This study was
      undertaken to determine if symptoms of gastroesophageal reflux disease (GERD)
      could be safely abrogated in a high-risk/reward popu lation of older patients.
      One hundred eight patients more than 70 years of age (range, 70-90 years)
      underwent laparoscopic Nissen fundoplications undertaken between 1992 and 2005
      and were compared with 108 concurrent patients less than 60 years of age (range,
      18-59 years) to determine relative outcomes. Before and after fundoplication,
      patients scored the severity of reflux and dysphagia on a Likert Scale (0 =
      minor, 10 = severe). Before fundoplication, older patients had lower reflux
      scores (P < 0.01), but not lower dysphagia scores or DeMeester scores. One
      patient (86 years old) died from myocardial infarction; otherwise, complications
      occurred infrequently, inconsequentially, and regardless of age. At similar
      durations of follow-up, reflux and dysphagia scores significantly improved (P <
      0.01) for older and younger patients. After fundoplication, older patients had
      lower dysphagia scores (P < 0.01) and lower reflux scores (P < 0.01). At the most
      recent follow-up, 82 per cent of older patients rated their relief of symptoms as
      good or excellent. Similarly, 81 per cent of the younger patients reported good
      or excellent results. Ninety-one per cent of patients 70 years of age or more
      versus 85 per cent of patients less than 60 years would undergo laparoscopic
      Nissen fundoplication again, if necessary. With fundoplication, symptoms of GERD
      improve for older and younger patients, with less symptomatic dysphagia and
      reflux in older patients after fundoplication. Laparoscopic fundoplication safely
      ameliorates symptoms of GERD in elderly patients with symptomatic outcomes
      superior to those seen in younger patients.

PMID- 16986388
TI  - Effects of sentinel lymph node biopsy on surgical residency training.
AB  - Axillary node dissection (AND) is an integral part of surgical training. Sentinel
      lymph node biopsy (SLN) was introduced into our residency in 1997. Our purpose in
      this study was to evaluate the impact of SLN on AND experience. AND/SLN operative
      experience of residents and attendings at our residency was reviewed using
      resident case-logs and questionnaires from 2002 and 2005. The perception of
      performing and teaching AND was assessed. Thirty-three residents and 24
      attendings participated. Graduating chiefs from the class of 2000 performed no
      SLN, which increased to 4.25 in 2002 and to 8.5 in 2005. In contrast, graduating
      chiefs performed 25 AND in 2000, which decreased to 16.5 in 2002 and to 13.25 in
      2005. The majority of the residents felt that AND was a senior level case (56%
      postgraduate year [PGY] I and II and 87% PGY III-V). The majority of the
      residents felt that SLN was a junior level case (89% PGY I and II and PGY III-V).
      Fifty-six per cent of PGY III-V felt that SLN introduction negatively impacted
      their ability to perform AND. Attendings cited 15 and 24 AND before feeling
      comfortable performing and teaching the procedure to a resident. Since the
      introduction of SLN into our residency, the number of AND has decreased, with
      senior residents feeling that SLN has decreased their ability to perform AND. As
      fewer AND are performed than our attendings cite to feel comfortable, future
      residents may not be competent to perform or teach AND.

PMID- 16986387
TI  - Experienced radio-guided surgery teams can successfully perform minimally
      invasive radio-guided parathyroidectomy without intraoperative parathyroid
      hormone assays.
AB  - Minimally invasive parathyroidectomy is an accepted treatment option for primary
      hyperparathyroidism. The need for intraoperative parathyroid hormone assays
      (iPTH) to confirm adenoma removal remains controversial. We studied minimally
      invasive radio-guided parathyroidectomy (MIRP) performed using preoperative
      sestamibi localization studies, intraoperative gamma detection probe, and the
      selective use of frozen section pathology without the use of iPTH. This is a
      single institution review of patients with primary hyperparathyroidism treated
      with MIRP by surgeons experienced in radio-guided surgery between October 1, 1998
      and July 15, 2005. Information was obtained by reviewing computer medical records
      as well as contacting primary care physicians. Factors evaluated included
      laboratory values, pathology results, and evidence of recurrence. One hundred
      forty patients were included with a median preoperative calcium level of 11.3
      mg/dL (range, 9.6-17) and a PTH level of 147 pg/mL (range, 19-5042). The median
      postoperative calcium level was 9.3 mg/dL. All patients were initially eucalcemic
      postoperatively except for one who had normal parathyroid levels. However, five
      (4%) patients required re-exploration for various reasons. Of the failures, one
      was secondary to the development of secondary hyperparathyroidism, and therefore
      would not have benefited from iPTH, one had thyroid tissue removed at the first
      operation, and three developed evidence of a second adenoma. One of these three
      patients had a drop in PTH level from 1558 pg/mL preoperatively to 64 pg/mL on
      postoperative Day 1, indicating that iPTH would not have prevented this failure.
      Thus, only three (2.1%) patients could have potentially benefited from the use of
      iPTH. MIRP was successful in 96 per cent of patients using a combination of
      preoperative sestamibi scans, intraoperative localization with a gamma probe, and
      the selective use of frozen pathology. This correlates with reported success
      rates of 95 per cent to 100 per cent using iPTH. We conclude that minimally
      invasive parathyroidectomy can be successfully performed without using iPTH
      assays.

PMID- 16986389
TI  - Local recurrence of breast cancer after MammoSite brachytherapy.
AB  - Women undergoing breast conservation therapy (BCT) for stage 1 breast cancer have
      adjuvant external beam radiotherapy (EBR). In addition, the use of brachytherapy
      radiation is being used. We present two local tumor recurrences for review. Our
      first patient underwent BCT, sentinel lymph node biopsy (SLNBx) and MammoSite
      brachytherapy for a T1N0M0 infiltrating ductal carcinoma (IDC) of the right
      breast. Pathology: 0.6 cm poorly differentiated ER, PR, and Her-2/ Neu negative
      IDC. At 18 months, she had palpable axillary lymph nodes. Fine needle aspiration
      and ultrasound-guided core biopsy of a nodule showed IDC. She underwent modified
      radical mastectomy (MRM) and EBR. Our second patient underwent BCT, SLNBx, and
      MammoSite brachytherapy for a T1N0M0 IDC of the left breast. Pathology: 0.8 cm
      poorly differentiated, ER+, PR-, and Her-2/Neu negative tumor. At 18 months, a
      retroareolar mass was detected. Ultrasound guided core needle biopsy showed
      recurrent IDC. She chose a re-excision and EBR and not MRM. Pathology: 1.3 cm
      poorly differentiated, ER+, PR-, and Her-2/Neu negative tumor. Our 2 recurrences
      were >2 cm away from the lumpectomy site and therefor outside the 1 cm treatment
      plan of the MammoSite catheter. Both recurrences were biologically identical to
      the initial tumors and are felt to be local failures rather than new primaries.

PMID- 16986390
TI  - Risk factors for recurrent hemorrhage after successful mesenteric arterial
      embolization.
AB  - The objective of this study was to describe the risk factors and to determine the
      outcomes after recurrent gastrointestinal hemorrhage after successful mesenteric
      arterial embolization A retrospective analysis was undertaken of a single-center
      experience with mesenteric arterial embolization performed for gastrointestinal
      hemorrhage over a 5-year period. Statistical analyses including Student's t test
      and Fisher's exact test were used to compare results. For the years 2001 through
      2005, 36 patients (10 women; average age, 60.8 years) underwent 37 technically
      successful mesenteric embolizations for acute gastrointestinal hemorrhage. Two
      (5.4%) cases required surgical intervention for cessation of hemorrhage, and six
      (16.2%) patients died during their hospitalization after technically successful
      embolization. Nine (24.3%) patients experienced in-hospital rehemorrhage, and of
      these, five (55.6%) died. Risk factors for rehemorrhage included intra-abdominal
      malignancy (P < 0.05), transfusion requirement greater than 10 units before
      angiography (P < 0.05), and the source of hemorrhage other than solitary
      gastroduodenal artery hemorrhage (P < 0.05). The failure of initial embolization
      was associated with an increased incidence of death (55.6% vs 5.0%; P < 0.05) and
      operative intervention to cease hemorrhage (P < 0.05). The failure of technically
      successful mesenteric embolization is not uncommon and is associated with
      identifiable risk factors. Risk factor awareness should assist in patient
      selection for and timing of mesenteric embolization.

PMID- 16986391
TI  - Prospective evaluation of adhesion formation and shrinkage of intra-abdominal
      prosthetics in a rabbit model.
AB  - Laparoscopic ventral hernia repair requires an intraperitoneal prosthetic;
      however, these materials are not without consequences. We evaluated host reaction
      to intraperitoneal placement of various prosthetics and the functional outcomes
      in an animal model. Mesh (n = 15 per mesh type) was implanted on intact
      peritoneum in New Zealand white rabbits. The mesh types included ePTFE
      (DualMesh), ePTFE and polypropylene (Composix), polypropylene and oxidized
      regenerated cellulose (Proceed), and polypropylene (Marlex). Adhesion formation
      was evaluated at 1, 4, 8, and 16 weeks using 2-mm mini-laparoscopy. Adhesion
      area, adhesion tenacity, prosthetic shrinkage, and compliance were evaluated
      after mesh explantation at 16 weeks. DualMesh had significantly less adhesions
      than Proceed, Composix, or Marlex at 1, 4, 8, and 16 weeks (P < 0.0001). Marlex
      had significantly more adhesions than other meshes at each time point (P <
      0.0001). There were no statistically significant differences in adhesions between
      Proceed and Composix meshes. After mesh explantation, the mean area of adhesions
      for Proceed (4.6%) was less than for Marlex (21.7%; P = 0.001). The adhesions to
      Marlex were statistically more tenacious than the DualMesh and Composix groups.
      Overall prosthetic shrinkage was statistically greater for DualMesh (34.7%) than
      for the remaining mesh types (P < 0.01). Mesh compliance was similar between the
      groups. Prosthetic materials demonstrate a wide variety of characteristics when
      placed inside the abdomen. Marlex formed more adhesions with greater tenacity
      than the other mesh types. DualMesh resulted in minimal adhesions, but it shrank
      more than the other mesh types. Each prosthetic generates a varied host reaction.
      Better understanding of these reactions can allow a suitable prosthetic to be
      chosen for a given patient in clinical practice.

PMID- 16986392
TI  - Discharging to a nursing home: not a terminal event--a follow-up study of senior
      motor vehicle crash patients.
AB  - Discharge to a nursing home (NH) because of chronic debilitating diseases or old
      age is generally a terminal event. The purpose of this study was to evaluate the
      NH outcome of senior citizens injured in motor vehicle crashes (MVC) discharged
      to a NH. From 2000 through 2004, 157 patients 75 years and older were admitted to
      the hospital for MVC. Of these, 32 patients were discharged to a NH, and these
      patients or their proxies were interviewed by telephone in June 2005 to request
      information as to driving status before and after the MVC, feeding, expression,
      and locomotion status, and/or date of death. After discharged from the NH, 72 per
      cent (23/32) of the patients lived at home, 52.2 per cent (12/23) among the
      drivers returned to drive, and those with functional impairments (excluding the
      five NH deaths and four still remaining in a NH) at the time of hospital
      discharge had 100 per cent or partial improvement in three functional independent
      measures at the time of the interview: 5 cases in feeding, 2 in expression, and
      20 in locomotion. Eleven of the 20 individuals dependent or partially dependent
      in locomotion status were fully independent. The majority of the senior patients
      discharged to a NH after a MVC returned to a normal life by going back home,
      driving again, and regaining functional activities after NH discharge. Discharge
      to a NH for elderly MVC trauma patients may be regarded as a stepping-stone to
      independent living rather than a final resting place.

PMID- 16986393
TI  - An unusual presentation of desmoid tumor in the ileum.
AB  - Desmoid tumors are nonencapsulated, locally invasive tumors of fibrous origin.
      Although lacking the ability to metastasize, they are notorious for recurrence. A
      wide variety of locations have been documented in the literature with respect to
      the origin of these tumors. Intra-abdominal desmoids are commonly found in the
      mesentery. We present the report of a case in which a sporadic desmoid tumor
      originated from the wall of the ileum. The patient was successfully treated with
      surgery alone, and has remained recurrence free on follow-up. Modalities of
      treatment documented in the literature include surgery, nonsteroidal, anti
      inflammatory drugs such as sulindac, and chemotherapeutic drugs such as
      vinblastine and methotrexate, radiotherapy, and, recently, tyrosine kinase
      inhibitors such as Imatinib (gleevec). Of all the options described, surgery with
      tumor-free margins has been defined as the best treatment modality.

PMID- 16986394
TI  - The mid-thigh loop arteriovenous graft: patient selection, technique, and
      results.
AB  - As patient longevity on hemodialysis has increased, surgeons are increasingly
      challenged to provide vascular access to patients who have exhausted options for
      access in the upper extremity. A common operation performed on these patients has
      been the loop thigh arteriovenous (AV) graft based off the common femoral
      vessels. However, there are several disadvantages of placing prosthetic grafts in
      proximity to the groin. Our group has modified the thigh loop AV graft procedure
      by moving the anastomoses to the mid-superficial femoral artery and vein. The
      advantage of this location is that it preserves the proximal femoral vessels for
      graft revision and avoids the node-bearing tissue and overhanging panniculus of
      the groin. The purpose of this study was to review our technique, patient
      selection, and experience with the mid-thigh loop AV graft procedure. Between
      2001 and 2003, 46 mid-thigh loop AV grafts were placed in 38 patients. Patient
      hospital, office, and dialysis clinic records were reviewed. The primary and
      secondary patency for AV grafts in this study by life-table was 40 per cent and
      68 per cent at 1 year and 18 per cent and 43 per cent at 2 years. There were 10
      infections (21%) requiring graft removal. Four patients underwent subsequent
      placement of a proximal loop thigh AV graft after mid-thigh graft failure.
      Patient survival was 86 per cent at 1 year and 82 per cent at 2 years. There were
      no patient deaths related to thigh graft placement. Our results with the mid
      thigh loop AV graft compare favorably with published results for thigh loop AV
      grafts. The procedure preserves the proximal vasculature, permitting graft
      revision or subsequent proximal graft placement, and may be associated with fewer
      infectious complications. The mid-thigh loop AV graft procedure should be
      considered before placement of a thigh loop AV graft based off the common femoral
      artery and vein.

PMID- 16986395
TI  - Laparoscopic greater omentum harvesting with split-thickness skin grafting for
      sternal wound dehiscence.
AB  - Sternal wound dehiscence is a serious complication occasionally requiring soft
      tissue coverage. The greater omentum typically has been used as a last resort
      because of the underlying morbidity from a laparotomy. We present a case in which
      a laparoscopically created omental flap with subsequent split-thickness skin
      grafting was used to correct a large soft tissue defect that occurred after
      sternal wound dehiscence developed. A nonambulatory 49-year-old man who underwent
      coronary artery bypass grafting developed sternal wound dehiscence. Because a
      large soft tissue defect developed after multiple debridements, soft tissue
      coverage was required. A laparoscopically harvested omental flap spared this
      man's upper extremity musculature and provided a soft tissue bed for split
      thickness skin grafting. This case helps to establish the role of
      laparoscopically harvested omentum. If the results suggested by this case are
      confirmed in a large series, omental flaps should be considered as options of
      first choice in the management of sternal wound dehiscence.

PMID- 16986396
TI  - Brachial arteriovenous fistula as a complication of placement of a peripherally
      inserted central venous catheter: a case report and review of the literature.
AB  - Peripherally inserted central venous catheter (PICC) lines have become a
      frequently used method of intravenous access for long-term administration of
      antibiotics, chemotherapy, and parenteral nutrition. Catheter-related
      complications involving the arterial tree are rare. We report a case of a 25-year
      old woman with a history of difficult PICC line placement that presented with an
      arteriovenous fistula in the left arm. Duplex ultrasound confirmed the diagnosis
      of a brachial artery-to-brachial vein arteriovenous fistula (AVF), and the
      patient underwent surgical repair. To our knowledge, this is the first reported
      case of an AVF resulting from PICC line placement. Correction of AVF is indicated
      to alleviate symptoms as well as to prevent future complications.

PMID- 16986397
TI  - Minimally invasive repair of pectus excavatum in adult patients.
AB  - Since 1996, the technique for minimally invasive repair of pectus excavatum
      (MIRPE) has gained increasing acceptance among pediatric patients. However, the
      feasibility of the operation and outcomes have not yet been evaluated in adult
      patients. This study was a retrospective analysis of the author's experience
      combined with a survey of members of the American Pediatric Surgical Association
      in treating adult patients with MIRPE. Thirty adults (age range, 18-32 years;
      mean, 23 years; 75% men) with severe pectus excavatum (chest index > 3.2) were
      treated with MIRPE. The main indication for surgery was cosmetic (80%). One 32
      year-old female patient underwent simultaneous MIRPE and breast augmentation. In
      60 per cent of cases, the operative time was 1 to 2 hours. Thoracic epidural was
      successfully used for postoperative pain management in 90 per cent of patients.
      Two pectus bars were necessary in 16 per cent of cases, and bilateral stabilizers
      were used in 53 per cent of patients. Complications included seroma (10%), bar
      displacement (6%), pneumothorax requiring tube thoracostomy (6%), superficial
      wound infection (3%), and stabilizer bar fracture (3%). Two patients required
      conversion to modified Ravitch repair. Patient satisfaction was rated as
      excellent (50%), good (36%), and fair (14%). Less than 50 per cent of patients
      achieved 100 per cent correction of their deformity. MIRPE can be used safely for
      repair of pectus excavatum in adult patients. The complication rate appears to be
      similar to previously reported series of pediatric patients. Although adult
      patients may have residual asymmetry of the chest postrepair, overall
      satisfaction with the repair was very good or excellent in 86 per cent of
      patients.

PMID- 16986398
TI  - Risk factors of abdominal surgery in patients with collagen diseases.
AB  - Patients with collagen diseases have been reported to demonstrate a greater risk
      when undergoing surgical operations. To determine the risk factors in abdominal
      surgery for patients with collagen diseases, 32 patients with collagen diseases
      who underwent abdominal surgery were analyzed for their clinical features and
      surgical results by comparing 26 cases from the favorable prognosis group (Group
      A) and 6 cases resulting in hospital death (Group B). The analysis revealed that
      emergent operations tended to result in worse outcomes (P = 0.011) than elective
      operations and that cases undergoing operations for collagen disease-related
      problems, including intestinal perforation and acute pancreatitis, also showed a
      worse postoperative course than those who underwent operations for problems
      unrelated to collagen diseases, such as carcinomas and cholelithiasis (P =
      0.0006). The dose of steroids administered at the time of operation was also
      significantly higher in Group B than in Group A (P = 0.03). These results
      suggested that the patients with collagen diseases should be followed
      periodically not only for the primary disease but also for any potential surgical
      diseases to identify such diseases at an early stage and to avoid an emergent
      operation, and that patients treated with high doses of steroids also need
      intensive care after abdominal surgery.

PMID- 16986399
TI  - Partnering with physicians. Today's environment requires attention on building
      relationships.

PMID- 16986400
TI  - IT disasters: the worst debacles and lessons learned from them.

PMID- 16986401
TI  - The future of healthcare: forecasts, implications and responses.

PMID- 16986402
TI  - Working with physicians to improve patient throughput.

PMID- 16986403
TI  - Johnson Controls connects disparate healthcare technology systems.

PMID- 16986404
TI  - Responding to clinical mistakes. Managements role requires thinking first of the
      patient and family.

PMID- 16986405
TI  - The healing power of art. Art displays in hospitals reduce stress, improve
      outcomes.

PMID- 16986406
TI  - Mobile mammography units. Denver program provides screenings to uninsured women.

PMID- 16986407
TI  - Is history ready to repeat itself? Prepare for Medicare spending cuts.

PMID- 16986408
TI  - Effective career development. CEOs can achieve their own career goals by helping
      others achieve theirs.

PMID- 16986409
TI  - Conflict of interest and governance. New approaches for a new healthcare
      environment.

PMID- 16986410
TI  - Clinical asset management. How targeted planning saves time and money.

PMID- 16986411
TI  - Let the hospital work for you. The physician's survival guide for the hospital.

PMID- 16986412
TI  - Mentorship as a responsibility: two thirties for one fifty.

PMID- 16986413
TI  - The public health response to disasters in the 21st century: reflections on
      Hurricane Katrina.
AB  - Ten years ago, in 1996, the author published a commentary on disasters, the
      environment, and public health, reviewing progress in the field. Despite many
      advances, significant events have occurred during the intervening decade,
      including the September 11, 2001, terrorist attacks and the 2005 Hurricane
      Katrina disaster. The recent lessons from Hurricane Katrina indicate that public
      health professionals still need to do more to protect the public in times of
      national disasters. Since recurring disasters will continue to adversely affect
      human health, public health providers and others involved with disaster
      management should again reflect on the importance of this issue and the need for
      action. Such action includes key public health professionals being present and
      actively involved in the field before and immediately following disaster impact.

PMID- 16986414
TI  - The New Jersey Residential Well-Testing Program--a case study: Randolph Township.
AB  - Since 1993, several wells have been found to be contaminated in Randolph
      Township, New Jersey. As a result, the local health department believed there was
      a need to develop an ordinance that would protect the health of private well
      users. Samplings of 1,488 private and nonpublic wells in Randolph Township were
      used to provide the basis for the ordinance proposal. Questionnaires were mailed
      to homeowners, and samples were collected to be evaluated for the presence of
      volatile organic compounds (VOCs), coliform bacteria, and other inorganic water
      quality criteria. Several VOCs were shown to be present in the residential water
      supplies, with more than half of them being chlorinated hydrocarbons. These
      chlorinated hydrocarbons are generally utilized in industry, at service stations,
      and as cleaning agents for septic systems; they were detectable within one
      quarter of a mile from stationary sources or industrial areas. Similar trends
      were seen for coliform bacteria and other inorganic products. The health
      department advised residents at sample sites when contamination was found.

PMID- 16986415
TI  - Changes in immunological and hematological parameters of female residents exposed
      to volatile organic compounds in the city of Kaohsiung, Taiwan.
AB  - The objective of this study was to assess the effects, if any, of volatile
      organic compounds (VOCs) in the ambient air of Kaohsiung, Taiwan, on certain
      hematological and immunological parameters of 153 female study participants. The
      major source of VOCs was vehicle emissions. The participants were selected from
      three areas, each area at a different distance from a freeway. Results indicated
      that total concentrations of VOCs and a subgroup of 25 VOCs (VOC25) ranged from
      250 to 335 ppb and 89 to 113 ppb, respectively. The distribution of VOC
      concentrations did not correlate with distance from the freeway. The participants
      living in the area with higher VOC concentrations had significantly higher
      abnormalities of white blood cells (WBC) and hemoglobin (Hb). In addition, IgG
      and IgA counts were significantly lower for the participants in the area with
      higher VOCs than for participants in the area with lower VOCs. This finding
      indicates that VOCs in ambient air may suppress immunological variables.

PMID- 16986416
TI  - A sanitarian's thoughts on sheltering evacuees.

PMID- 16986417
TI  - Recent research from Lessons Learned Information Sharing: the importance of
      partnerships in the rural water response to Hurricane Katrina.

PMID- 16986418
TI  - The need for partnerships for food safety.

PMID- 16986421
TI  - Florida's 2005 hurricane season: lessons continuing to be learned.

PMID- 16986419
TI  - The use of public health data and documents in foodborne-illness litigation.

PMID- 16986422
TI  - Electrical conductivity helps locate septic-system failure.

PMID- 16986423
TI  - An introduction to the herpes viruses.
AB  - The herpes viruses continue to affect patients worldwide. The use of
      immunosuppressant medications, the AIDS epidemic and crowded living conditions
      will continue to present a challenge to our health care system.

PMID- 16986424
TI  - Addressing dentin hypersensitivity.

PMID- 16986425
TI  - United States Army Dental Command welcomes new commander and sergeant major.

PMID- 16986427
TI  - Embezzlement: a crime of opportunity.

PMID- 16986426
TI  - Minnie and Maxine.

PMID- 16986428
TI  - A call for multiproduct testing.

PMID- 16986429
TI  - Identification and molecular characteristics of mutant alleles at the Du281 locus
      in parthenogenetic progeny of Darevskia unisexualis.

PMID- 16986430
TI  - Melafen and energy status of cells of plant and animal origin.

PMID- 16986431
TI  - Theoretical conformational analysis of antidepressant as a way for evaluation of
      their efficiency for pain and itch syndrome management in patients with end-stage
      renal disease under chronic hemodialysis.

PMID- 16986432
TI  - Modeling of the role of Cl- channels in Ca2+ translocation through endoplasmic
      reticulum membrane.

PMID- 16986433
TI  - Thermodynamic parameters for calculating the stability of complexes of bridged
      oligonucleotides.

PMID- 16986434
TI  - Study of thermal stability of mutant NADP(+)-dependent formate dehydrogenases
      from Pseudomonas sp. 101.

PMID- 16986435
TI  - Effect of tannic acid on the development and resistance of the gypsy moth
      Lymantria dispar L. to viral infection.

PMID- 16986436
TI  - Detection and study of the products of photooxidation of N-retinylidene-N
      retinylethanolamine (A2E), the fluorophore of lipofuscin granules from retinal
      pigment epithelium of human donor eyes.

PMID- 16986437
TI  - Preparation melafen and the physicochemical state of biological membranes.

PMID- 16986438
TI  - A study of complex formation by alpha- and betaL-crystallins under UV
      irradiation.

PMID- 16986439
TI  - Retrotransposon gtwin specific for the Drosophila melanogaster subgroup.

PMID- 16986440
TI  - Molecular polymorphism of the yeast Kluyveromyces dobzhanskii: geographic
      populations.

PMID- 16986441
TI  - Role of Toll-like proteins in the realization of effects of chorionic
      gonadotropin on the functional activity of monocytes.

PMID- 16986442
TI  - Bgl2p and Gas1p are the major glucan transferases forming the molecular ensemble
      of yeast cell wall.

PMID- 16986443
TI  - A study of the locus control region (LCR) of the cut locus of Drosophila
      melanogaster using luciferase-expressing reporter genetic constructs.

PMID- 16986444
TI  - Movement protein stimulates tobacco mosaic virus reproduction in infected cells.

PMID- 16986445
TI  - Uppers and downers.

PMID- 16986446
TI  - Prescription stimulant abuse.
AB  - Our goal with this issue of Pediatric Annals is to increase understanding among
      clinicians about both the problems with and the solutions to nonmedical use of
      prescription stimulants. We encourage, not discourage, the treatment of ADHD with
      both medications and nonmedication therapies. By significantly reducing the
      nonmedical use of the stimulant medicines for ADHD, we expect that this important
      area of medical practice will be protected for the benefit of ADHD patients. The
      lessons learned here can have broad positive applications to other medical
      treatments with controlled substances.

PMID- 16986447
TI  - An 8-year-old girl with a 15-pound weight loss.

PMID- 16986448
TI  - A 1-year-old girl with "puffy feet".

PMID- 16986449
TI  - The science of stimulant abuse.
AB  - Stimulant medications, although classified by the US Drug Enforcement Agency as
      controlled with a Schedule IIa rating, are ubiquitous in our society because of
      their popularity as an effective treatment for childhood ADHD. The number of
      stimulant products available for practitioners has tripled in the last decade.
      Although stimulants' action on central dopamine systems can be reinforcing,
      especially when delivered via intraperitoneal or intravenous routes in laboratory
      animals, they are far less addicting when taken orally by children in the context
      of a medical treatment. Fortunately, the therapeutic stimulants, available
      orally, have different pharmacodynamic and pharmacokinetic properties than the
      illicit stimulants, methamphetamine and cocaine. The lack of intravenous forms of
      the therapeutic stimulants acts as a natural barrier and tends to prevent
      addiction. Furthermore, MPH produces dysphoria in school age children, further
      limiting its reinforcing properties. These pharmacokinetics and pharmacodynamics
      of methylphenidate and amphetamine treatments for ADHD thus are less addicting
      because of their delivery systems. Future products, employing novel methods that
      only allow the drug molecule to be available if ingested, should further increase
      the safety of these important therapeutic agents.

PMID- 16986450
TI  - Physician handling of prescription stimulants.
AB  - Good medical practices can significantly reduce the possibility of diversion and
      misuse of the stimulants commonly prescribed to treat ADHD. While the problems of
      misuse and abuse are real, they should not become a barrier to appropriate use of
      these medicines, which are safe and effective for the large majority of patients
      with ADHD using them. With appropriate care, physicians treating patients with
      ADHD can be confident that their treatments are safe, not only for the patients
      they treat, but also for the communities in which they live.

PMID- 16986452
TI  - Prescription stimulant sales on the Internet.

PMID- 16986451
TI  - Nonmedical use of prescription stimulants among students.
AB  - Despite the caveats discussed above, national epidemiologic surveys are useful in
      estimating the prevalence and historical trends of nonmedical use of prescription
      stimulants. Because it would be difficult and cost-prohibitive to ask several
      more in-depth questions on these national surveys, other smaller-scale research
      studies should be undertaken to understand more about the patterns and
      consequences of nonmedical use of prescription stimulants. The data from the few
      studies of college students suggest college students are more likely to use
      prescription stimulants than their noncollege-attending counterparts and suggest
      college students may experience a need to stay awake to study given the high
      level of demands in the college environment. More and more people are taking
      advantage of the opportunity to go to college, making the selection process more
      competitive. More data are needed regarding the availability of prescription
      stimulants on college campuses and, in particular, the availability and use of
      other types of prescription stimulants other than methylphenidate. Data from the
      college studies presented here also suggest that, in addition to using
      prescription stimulants as a study aid, students use prescription stimulants to
      stay awake longer to party or drink more. Because heavy drinking is known to be
      associated with a wide variety of negative consequences, it is important to learn
      more about this particular interaction so that appropriate prevention initiatives
      can be developed.

PMID- 16986453
TI  - Abuse-resistant drug delivery.
AB  - In attempting to reduce the nonmedical use of controlled substances, a reasonable
      step is to educate the physicians prescribing controlled substances, including
      the prescription stimulants used to treat ADHD, as well as patients and family
      members, about the risks of nonmedical use and the dangers of giving or selling
      these medicines to persons for whom they were not prescribed. Patients who find
      benefits in the use of such medicines have a significant interest in protecting
      their continued access to them. Such access is potentially threatened by concerns
      about widespread nonmedical use. Physicians can help protect the appropriate
      medical use of prescription stimulants by considering the abuse potential of
      various medicines used to treat patients with ADHD, especially when these
      patients also have a history of nonmedical substance use. In addition, we suggest
      that today there is an opportunity to add a new and perhaps more hopeful
      paradigm: the wider use of drug delivery systems that make products less
      attractive to drug abusers. This new drug abuse prevention paradigm holds great
      promise for efforts to reduce the nonmedical use of prescription controlled
      substances, including the prescription stimulants used to treat ADHD. To achieve
      the full potential of this new paradigm to reduce prescription drug abuse, it
      will be necessary to develop standards to assess the relative abuse resistance of
      various drug formulations and delivery systems, as well as meaningful incentives
      to foster the development of these abuse-resistant delivery systems for
      controlled substances.

PMID- 16986454
TI  - A federal perspective on the abuse of prescription stimulants.

PMID- 16986455
TI  - [Optical nanoscopy].

PMID- 16986456
TI  - X-ray phase contrast imaging of metallized and non-metallized biological samples.
AB  - Imaging of biological samples has been performed with a variety of techniques for
      example electromagnetic waves, electrons, neutrons, ultrasound and X-rays. Also
      conventional X-ray imaging represents the basis of medical diagnostic imaging, it
      remains of limited use in this application because it is based solely on the
      differential absorption of X-rays by tissues. Coherent and bright photon beams,
      such as those produced by third-generation synchrotron X-ray sources, provide
      further information on subtle X-ray phase changes at matter interfaces. This
      complements conventional X-ray absorption by edge enhancement phenomena. Thus,
      phase contrast imaging has the potential to improve the detection of structures
      on images by detecting those structures that are invisible with X-ray absorption
      imaging. Images of a weakly absorbing nylon fibre were recorded in in-line
      holography geometry using a high resolution low-noise CCD camera at the ESRF in
      Grenoble. The method was also applied to improve image contrast for images of
      biological tissues. This paper presents phase contrast microradiographs of
      vascular tree casts and images of a housefly. These reveal very fine structures,
      that remain invisible with conventional absorption contrast only.

PMID- 16986457
TI  - [Application of normoxic polymer gels in 3D-dosimetry for radiosurgery].
AB  - The aim of this study was to describe the manufacture of normoxic polymer gels,
      to characterize their dose response relationship, to optimize MR imaging
      parameters in order to minimize the standard deviation in the measured dose and
      to use the gel in a dose verification experiment in radiosurgery. The normoxic
      polymer gel used is simple to manufacture under normal atmospheric conditions and
      is characterized by a linear dose relationship up to 40 Gy. MR imaging was
      performed using 2-dimensional (20) single spin echo pulse sequences with two
      different echo times. The imaging parameters were optimized in order to minimize
      the standard deviation of the measured transversal relaxation rate R2 and to
      achieve a geometrical resolution of 1.5 mm. Comparisons of calculated and
      measured relative 3D dose distributions using a multi isocentric irradiation with
      Gamma Knife B showed a good overall agreement of both the isodose levels and the
      differential and cumulative dose volume histograms. The standard deviation in the
      measured dose was approximately 9% at 30 Gy. The evaluation according to the
      gamma criterion showed that 96% of the dose voxels remained within a spatial
      uncertainty of 1.5 mm and a dose uncertainty of 8%.

PMID- 16986458
TI  - [Tissue contrast in MRI owing to intermolecular multiple-quantum coherences
      (iMQC)].
AB  - Dipole-dipole interactions in 1H NMR of liquids permit a new tissue contrast in
      MR imaging (MRI). For this purpose, the CRAZED (COSY Revamped by Asymmetric Z
      gradient Echo Detection) sequence which simply consists of two radiofrequency
      pulses of delay tau and a magnetic field gradient pulse of strength G, is applied
      to create intermolecular multiple-quantum coherences of dipolar-coupled ensembles
      of water protons with spatial distance d = pi/(gammaGtau). As a consequence, the
      measured signal originates from "sources" that have a tunable dimension. CRAZED
      was first applied to MR imaging at 1.5 T by Zhong et al. To study the contrast
      properties and influence of sequence parameters of this technique, we implemented
      different sequences of this type on a clinical 1.5-T whole-body tomograph. The
      sequences were optimized in experiments with agar gel phantoms. We obtained
      images with dipolar contrast from the brain of healthy volunteers. The gradient
      system enabled correlation distances d in the range of 0.05 mm to 1 mm.

PMID- 16986459
TI  - [Slice profile measurements of half pulse excitation for MR-imaging with ultra
      short echo times (UTE)].
AB  - Half pulse excitation plays an important role in imaging with ultra-short echo
      times (UTE imaging) of the order of TE < 100 micros. Based on half RF-pulses this
      method was theoretically modeled and experimentally applied in 1991 for the first
      time. Following this work, measurements of slice profiles produced by half pulses
      were performed and results were compared to the slice profiles produced by the
      original full pulse. Furthermore, the hypothesis was tested that short RF pulses
      may be of advantage in minimizing the relaxation effects during the pulse. Within
      the scope of these measurements no dependency of slice profile on the pulse
      duration could be found.

PMID- 16986460
TI  - [Dosimetric consequences of the application of a rectum hull-planning volume for
      treatment planning of intensity modulated radiotherapy of prostate cancer].
AB  - The present study evaluated a hull-volume definition strategy for the planning
      organ at risk volume (PRV) for the rectum in the planning of radiotherapy of
      prostate cancer. The bounding volumes of rectum contours of 1 to 5 CT scans were
      compared on the basis of the rectum coverage probabilities for 5 patients. In
      addition, IMRT treatment plans were optimized using the rectum hull PRV5 of 5 CTs
      and each of the conventional rectum contours PRV1. The plans were compared on the
      basis of the organ doses caused by the individual organ motion. PRV5 allowed to
      cover the rectum with a probability of nearly 90% (PRV1 67%). Rectal wall dose
      showed a great variability for PRV1, while planned and treatment dose agreed well
      for PRV5 due to the improved geometric information which resulted in a better
      rectal sparing. In conclusion, the rectum hull-volume PRV5 is a well suited PRV
      for planning of IMRT dose distributions allowing dose escalation as well as
      rectal sparing.

PMID- 16986461
TI  - The dose-area product, a new parameter for the dosimetry of narrow photon beams.
AB  - In the dosimetry of narrow photon fields with side lengths of the order of 1 cm,
      the traditional parametrisation via the absolute dose on the beam axis and the
      relative lateral dose distribution has to deal with the difficulty to find
      sufficiently small detectors and to adjust them accurately on the narrow-beam
      axis. This can be avoided by reconsidering the parametrisation, using as
      normalization factor the surface integral of the dose in the plane perpendicular
      to the beam axis, abbreviated as the "dose-area product" (DAP). We investigated
      and confirmed the ability of a large-area parallel-plate ionisation chamber, with
      a sensitive volume shaped as a flat cylinder of 81.6 mm diameter and 2 mm
      thickness, to perform the integration over the full lateral dose profile of
      narrow photon beams with side lengths up to 5 cm. The lateral adjustment of this
      large-area detector relative to a narrow photon beam is not critical. The large
      area ionisation chamber was calibrated in terms of the DAP by reference to a 0.3
      cm3 ionisation chamber. A field-size dependent "modified output factor" was
      defined as the ratio of the DAP measured at 5 cm phantom depth for 100 cm SSD,
      and the monitor reading. A prominent phenomenon of narrow photon fields is the
      field-size and source-distance independence of the relative axial profile of the
      DAP as function of the thickness of a pre-absorber or of the depth in a phantom.
      For narrow-beam treatment planning in IMRT, the DAP is combined with the energy-
      and field size-dependent relative lateral dose distribution which is represented,
      for example, by a Gaussian convolution kernel. Another useful feature of the DAP
      is the possibility of its direct control during patient irradiation by means of
      an on-line monitor with spatial resolution, arranged in the accessory holder.

PMID- 16986462
TI  - Embryonic stem cell research: perilous pursuit?

PMID- 16986463
TI  - A new branch on the P3 tree.

PMID- 16986464
TI  - Community benefit is no one's job (it's everyone's job).

PMID- 16986466
TI  - Sponsorship's biblical roots and tensions. The term may be new, but the function
      has existed since apostolic time.

PMID- 16986465
TI  - One voice.

PMID- 16986467
TI  - 2006 CHA Mission Leaders Survey 2. A study compares the role's strengths,
      weaknesses with those seen in 1993.

PMID- 16986468
TI  - Embryonic stem cell research: off limits? Two ethicists discuss a technological
      breakthrough in the context of Catholic health care.

PMID- 16986469
TI  - To circumcise or not to circumcise. A Catholic ethicist argues that the practice
      is not in the best interest of male infants.

PMID- 16986470
TI  - Medicine's goals and prophetic tradition. Catholic health care has an opportunity
      to help the medical profession return to its roots.

PMID- 16986471
TI  - The continuum of care today. After 20 years, what is the status of integration of
      services?

PMID- 16986472
TI  - A hospice for the pre-born and newborn. A Kansas city facility provides care for
      babies with severe birth defects and for their families, too.

PMID- 16986473
TI  - What are "indults" and "dispensations"?

PMID- 16986474
TI  - Blending leadership models. A Kansas-based system has both centralized and
      decentralized dimensions.

PMID- 16986475
TI  - Pressure ulcer prevention and treatment. Part I--prediction and prevention.

PMID- 16986476
TI  - Rx: Recruitment for practical nursing students. Take more students and save
      money!

PMID- 16986477
TI  - Evidence based practice. An introduction to evidence based practice.

PMID- 16986478
TI  - Let your feet do the talking!

PMID- 16986479
TI  - Taking criticism.
AB  - The manner in which criticism is dealt with is one of the important behaviors to
      master in a healthcare work environment: 1.) respond calmly, 2) use a problem
      solving approach, 3) avoid blaming others, 4) increase the complainers feelings
      of power, 4) increase feelings of power, 5) communicate respect, 6) do not
      respond to criticism with an e-mail, 7) forgive the complainer and not hold a
      grudge; and 8) let the buck stop as soon as possible, and 9) take criticism
      seriously. Dealing with criticism will never be easy. It just isn't! But using a
      reasoned approach will help, and get us back to why we entered healthcare - to
      take care of patients.

PMID- 16986480
TI  - A student's plea for global health studies in the medical school curriculum.
AB  - Public policy in Canada is sensitive to changes that have occurred in society as
      a consequence of immigration, globalization and a new understanding of aboriginal
      and ethnic cultures. The traditional medical school undergraduate curriculum does
      not accommodate these changes. The current emphasis on evidenced-based medicine
      may reinforce the traditional approach because there is a dearth of global
      healthcare research. This review of medical schools in Canada suggests that
      modifications of curricula are being attempted to meet the need for knowledge of
      global health. Integration of global health principles and information into the
      current curriculum promotes a better understanding of Canada's healthcare
      delivery system itself as well as its role globally.

PMID- 16986481
TI  - Computers in medicine. Virtual rehabilitation: dream or reality?
AB  - Coronary heart disease is the number one cause of death for men and women in the
      United States and internationally. Identification of persons at risk for
      cardiovascular disease and reduction of cardiovascular risk factors are key
      factors in managing this tremendous societal burden. The internet holds great
      promise in helping to identify and manage persons at high risk of a cardiac or
      vascular event. The Internet has the capability to assess risk and provide
      support for cardiovascular risk reduction for large numbers of persons in a cost
      effective and time efficient manner. The purpose of this report is to describe
      important advances in the use of the Internet in identifying persons at risk for
      a cardiovascular event and in the Internet's ability to provide interventions
      designed to reduce this risk.

PMID- 16986482
TI  - Unplanned emergency surgery in relation to length of wait lists at registration.
AB  - OBJECTIVE: To compare the cumulative incidence of emergency surgery between two
      groups of patients classified according to the length of wait lists at the time
      of their registration for coronary artery bypass grafting (CABG) and to test for
      significant differences in the risk of emergency surgery resulting from
      registration on a longer wait list. METHODS: A prospective study of all adult
      British Columbia residents who registered to undergo isolated CABG. We compared
      the time-dependent cumulative incidence for undergoing planned surgery through
      unplanned emergency admission before or during a certain wait-list week between
      two categories of wait-list size. The list size was a simple count of patients
      with higher or equal urgency to undergo CABG who were on a wait list at the time
      of registration of a new patient. RESULTS: Wait lists with one month or less of
      clearance time were observed in all urgent patients and were more prevalent in
      semi-urgent than non-urgent patients (79.1% vs 44.7%, respectively). The patients
      registered on a list with a clearance time of more than one month had a rate of
      unplanned emergency admission similar to those on a list with a clearance time of
      one month or less, OR = 1.07 (95% CI, 0.78-1.47) after adjustment for age, sex,
      comorbidity, calendar period, urgency and week on the list. During fifty-two
      weeks of the wait-list follow-up, an equal proportion of patients underwent
      unplanned emergency surgery after registration on lists in both clearance-time
      categories, OR = 1.03 (95% CI, 0.78-1.37) after adjustment. The number of
      patients who underwent CABG without having been registered on a wait list in the
      same hospital exerted no independent effect. CONCLUSIONS: The length of a wait
      list at registration had no effect on the probability that a semi-urgent or non
      urgent patient would undergo CABG through unplanned emergency admission before or
      during a certain wait-list week.

PMID- 16986484
TI  - Future practice profiles of Canadian medical trainees.
AB  - PURPOSE: To investigate the future practice profiles of Canadian medical
      trainees. METHODS: Data were extracted from the 2004 National Physician Survey, a
      questionnaire distributed to medical students, residents and physicians across
      Canada. Data were categorized by level of training and chi-square comparative
      analyses were done. RESULTS: The majority of trainees (about 64%) expressed plans
      to practice in the location in which they were training, with approximately 12%
      planning on practicing in another country. Family medicine (FM) residents were
      more likely to express wishes to practice in their location of training when
      compared to medical students and specialty residents. CONCLUSIONS: The location
      of training directly affects the future practice plans of Canadian medical
      trainees. Retaining specialist physicians may represent a challenge in the
      future.

PMID- 16986483
TI  - Prolastin aerosol therapy and sputum taurine in cystic fibrosis.
AB  - BACKGROUND: Neutrophil elastase in the cystic fibrosis airways inhibits
      opsonophagocytosis and induces the expression of interleukin-8, a neutrophil
      chemoattractant. Prolastin is a therapeutic preparation of alpha-1 proteinase
      inhibitor (alpha1,-PI), a neutrophil elastase inhibitor. The objective of this
      study was to determine the effects of Prolastin aerosol therapy on airway
      inflammation in cystic fibrosis. METHODS: The primary endpoint of this study was
      sputum taurine, an amino-acid present in high concentrations in neutrophils.
      Sputum taurine correlates with respiratory exacerbations of cystic fibrosis.
      Seventeen patients with cystic fibrosis were each assigned to three sequential 10
      day periods including first, aerosol therapy of 5 ml saline solution bid; second,
      aerosol therapy of 250 mg Prolastin bid; third, no aerosol therapy. On days 8, 9
      and 10 of each period, early morning sputum was collected for the quantification
      of alpha1-PI, neutrophil elastase activity, IL-8 and taurine. RESULTS: During
      Prolastin therapy, a 3-fold increase in sputum alpha1-PI was observed (P =
      0.002). Baseline values of sputum alpha1-PI correlated with the values obtained
      after Prolastin aerosol (R = 0.77, P < 0.01). Sputum neutrophil elastase activity
      remained unchanged but taurine decreased after Prolastin therapy (during therapy
      P = 0.052, after therapy P = 0.026). Prolastin aerosol therapy had no adverse
      effect on pulmonary function. CONCLUSIONS: Aerosol therapy with Prolastin in
      patients with cystic fibrosis leads to a progressive decrease in sputum taurine.
      This suggests that even in the absence of sustained elastase inhibition,
      Prolastin aerosol therapy may have a beneficial effect on airway inflammation in
      patients with cystic fibrosis.

PMID- 16986485
TI  - [Anatomical pathology and molecular diagnosis].
AB  - 150 years ago, R. Virchow proposed a "cellular pathology" theory that forced one
      to revise many concepts of the mechanisms responsible for the development of
      disease and marked the beginning and further development of anatomical pathology
      as an independent discipline. Rapid progress in immunology, genetics,
      biotechnology, and cellular and molecular biology in the late 1980s to the early
      1990s gave rise to a new field, namely molecular medicine. Damage changes the
      profile of expression some genes, activates various signal systems, and, due to
      of intercellular and cellular-matrix interactions, then spreads first at the
      level of organs, then at that of the whole body if a pathological process cannot
      localize. By involving some cells, the pathological process cannot cause
      characteristic morphological changes and therefore traditional studies yield a
      negative result. Molecular pathology became a necessary additional tool in the
      work of a pathologist, by allowing him to obtain the information that had been
      earlier beyond the reach, which increased the validity of diagnosis. Some points
      of the Virchow "cellular pathology" theory are supported by molecular pathology.

PMID- 16986486
TI  - [Prognostic value of the expression of thyreoglobulin and oncomarkers (p53, EGFR,
      ret-oncogene) in different types of papillary carcinoma of the thyroid:
      clinicomorphological and immunohistochemical studies].
AB  - The surgical material obtained from 57 patients was immunohistochemically
      studied. Immunohistochemistry with quantitative and semiquantitative analyses of
      the results of test was used to define the expression of oncomarkers p53, EGRF,
      ret-oncogene, and thyreoglobulin. The expression of thyreoglobulin, EGRF, and ret
      oncogene reflects the malignant potential of papillary carcinoma of the thyroid
      and and may be recommended as a predictive marker. The low expression of
      thyreoglobulin and the high expression of p53 and ret-oncogene are markers of a
      poor prognosis and tumor recurrence. EGFR expression is not of predictive value.
      MB3 proposed by the authors may be recommended for the determination of the
      malignant potential of papillary carcinoma of the thyroid.

PMID- 16986487
TI  - [Computer morphometry in the differential diagnosis of thyroid neoplasms].
AB  - The quantitative studies of follicular thyroid tumors were applied for their
      morphological differentiation. The computer-aided analysis of the images permits
      objective and prompt estimation of the quantitative parameters of the structural
      components of a tumor in the histological sections. The comparison of the values
      obtained in the tissue samples could identify the most typical differentially
      diagnostic criteria that could help to define the type of a tumor, by replacing a
      routine morphological study based on the analysis of qualitative morphological
      signs. Its effectiveness is largely determined by the skill of a physician and
      the subjectivity of assessments of observed phenomena.

PMID- 16986488
TI  - [Mucinous tubular and spindle-cell carcinoma of the kidney].
AB  - 4 cases (2 males and 2 females) of mucinous tubular and spindle-cell carcinoma of
      the kidney were studied. The patients' age was 43 to 87 years. Microscopically,
      this tumor comprised two major cell populations. One of them involved spindle
      cells with a sparse cytoplasm, which were arranged in the fascicular pattern,
      often resembling low-grade smooth muscle tumors. The other population was small
      cuboidal cells with round nuclei and an eosinophilic cytoplasm. The mitotic
      activity was low. Only one tumor had both cell components. The other three tumors
      were represented by the second type cells. Immunohistochemical staining with
      avidin-biotin was performed by using cytokeratin, vimentin, SMA, p53, Bcl 2, EMA,
      and CD10. All cases were stained positively with antibodies to the cytokeratins
      AE1-AE2 and vimentin. The expression of EMA, Bcl 2, and CK7 was varying in
      different tumors. Responses to smooth muscle actin, p53, CK20, and CD10 were
      negative in all cases. Mucinous tubular and spindle-cell carcinoma of the kidney
      should be differentiated from angiomyolipoma with the preponderance of a
      leiomyomatous component, renal smooth muscle neoplasms, metanephrotic adenoma,
      and renal cell carcinoma with sarcomatoid differentiation.

PMID- 16986490
TI  - [Ovarian endometriosis: characteristics of the blood circulatory bed].
AB  - Glandular cystic ovarian endometriosis (OE) is characterized by a more intensive
      blood supply than cystic OE. This type of OE is characterized by a high
      proliferative glandular epithelial activity detected by an immunohistochemical
      study using antibodies to PCNA and CA-125. Moreover, a positive correlation is
      found between the serum concentration of CA-125 and the expression of this
      antigen in the epitheliocytes of an endometrioid cyst in both glandular-cystic
      and cystic OE. Thus, the findings permit the determination of the
      morphofunctional activity of a type of OE and its aptness to the progression of
      the disease and to the development of recurrences.

PMID- 16986489
TI  - [Female genital tract polyneoplasia: primary multiple neoplasms or metastases?].
AB  - The analysis of 49 cases of synchronous and metachronous malignant mucinous
      tumors of the colon (rectum) and ovaries in the patients treated in 1990 to 2004
      again has confirmed the data that metastatic ovarian cancer occurs from a primary
      focus in the colorectal region. Immunohistochemical studies (using cytokeratin 7
      and cytokeratin 20) may be used in the differential diagnosis of ovarian mucinous
      ovarian carcinoma from metastatic colonic mucinous tumors.

PMID- 16986491
TI  - [Impact of maternal thyroid disease on the formation of relationships in the
      maternal-placental-fetal system].
AB  - Impaired microcirculation with evolving sludge phenomenon and thrombosis underlie
      placental changes in maternal thyroid disease. Capillary blood circulatory defect
      is largely due to villous immaturity. Placental tissue ischemia gives rise to
      fibrinoid, sclerosis, and alternative processes. Dysadaptive changes are mostly
      observed in thyrotoxicosis and hypothyroidism. Adaptive processes evolving at the
      ultrastructural level are best pronounced in euthyroid goiter.

PMID- 16986492
TI  - [Astrocytic morphological responses in different murine brain regions in the
      simulation of West Nile fever].
AB  - The brains from the mice infected intraperitoneally (with development of these or
      those symptoms of viral encephalitis) or intramuscularly with the Astrakhan West
      Nile fever virus strain (AcT 986) was pathomorphologically studied.
      Clinicomorphological changes in the neurons and vessels of the microcirculatory
      bed were found in the dorsal regions of medulla oblongata. Immunohistochemicall
      analysis showed that mature and/or activated astrocytes increased in number,
      largely in the animals without clinical manifestations of encephalitis. The
      findings provide evidence that cerebral astrocytes play a protective and adaptive
      role that seems to depend on the biological properties of the pathogen.

PMID- 16986493
TI  - [Prionic neuroinvasion and cerebellar lesion in Creutzfeldt-Jakob disease].
AB  - Examining the histological brain sections of patients with Creutzfeldt-Jakob
      disease (CJD) showed the accumulation of PrP(CJD) in the cerebellar cortical
      layers. In nCJD, the prion accumulated mainly in the granular layer in the area
      of synapses of moss fibers with granular cell dendrites in the cerebellar
      glomeruli and in the molecular layer in the area of the synapses formed by
      granular cell axons and great stellate neurons of the granular layer with the
      dendrites of Purkinje's piriform cells of busket cells and Golgi's cells.
      PrP(CJD) amyloid plaques were formed in these regions. In sporadic CJD, PrP(CJD)
      accumulated only in the cerebellar molecular layer in the area of the synapses
      formed by climbing fibers with the dendrites of Purkinje cells. The findings lead
      to the conclusion that prion spreads along different nerve fibers through the
      synapses. The preserved Purkinje cells contacting the plaques suggest that prion
      is not itself highly neurotoxic.

PMID- 16986494
TI  - [Uterine arteriovenous anomaly in a young woman].
AB  - The paper presents a case of uterine arteriovenous anomaly as mixed hamartoma
      with the signs of racemose and intramuscular angiomas, which was a morphological
      finding in an 18-year-old woman when the uterus removed for misdiagnosed
      postpartum septic endometritis was examined.

PMID- 16986495
TI  - [Combined mycosis as a complication of renal allotransplantation and
      immunosuppressive therapy].
AB  - A histological study of arteries and veins in the presence of suppuration in
      shunt sepsis in a patient on programmed hemodyalisis and unsuccessful triple
      renal allotransplantation revealed bacterial endocarditis, as well as Candida
      induced endophlebitis of cubital veins and disseminated chromoboblastomycosis
      with the involvement of lymph nodes, adrenals, and hypophysis.

PMID- 16986496
TI  - [The morphology of a main bronchial stump area after diaphragmopexy or
      omentopexy].
AB  - The present paper presents 5 microscopic investigations of the morphology of a
      major bronchial stump area or tracheobronchial anastomosis after tightly fixing a
      vascularized diaphragmatic or omental flap. The cadaveric material of female
      patients who had died in different periods after diaphragmopexy or omentopexy was
      investigated. The authors' observations support the fact that diaphragmatic or
      omental flaps tightly sutured to the tracheobronchial wall can provide its
      revascularization and regeneration of the bronchial stump or tracheobronchial
      anastomosis.

PMID- 16986497
TI  - [Ovarian follicular cysts in a 3-month girl].
AB  - The paper presents a clinicoanatomic case of the polycystic ovary in a 3-month
      old girl who died from intestinal infection. It shows the pathomorphological
      changes of ovaries, the structure of cysts, primary ovocytes, with defects of
      their structural and spatial pattern. It is suggested that there is a dynamic
      imbalance of the biological program of folliculogenesis and follicular atresia,
      which leads to the cystic transformation of ovaries and the persistence of
      biologically defective primary ovocytes.

PMID- 16986498
TI  - [A rare variant of malignant melanoma progression].
AB  - Progression of melanoma passed under the "mask" of uterine corpus carcinoma. The
      rarity of this case is an isolated melanoma metastasis into the endometrium and
      peculiar clinical manifestation.

PMID- 16986499
TI  - [Experience in setting up a morbid anatomy bureau in the Gomel Region, Republic
      of Belarus].
AB  - A diversity of the clinical and morphological manifestations pf melanoma
      determines the great importance of each description of manifestation of this most
      malignant tumor. In this connection, there is a worldwide increasing rise in the
      number of patients with melanoma whose diagnosis present well-known difficulties,
      the authors describe a case of this tumor progression, which masked as uterine
      carcinoma.

PMID- 16986500
TI  - [Ganglioneuroblastoma in Yemenite chameleon (Chamaeleo calyptratus): the first
      recorded case of a tumor of neuroectodermal histogenesis in reptiles].
AB  - Nerve tissue tumors are rarely encountered in reptiles and mainly represented by
      some documented cases of malignant peripheral nerve sheath tumor (MPNST). The
      paper is the first to describe a tumor mimicking MPNST by some ultrastructural
      features of tumor cells; however, significantly differing in the combination of
      immunohistochemical characteristics. Based on the data of electronic microscopy,
      immunohistochemistry, cytology, and histology, the tumor was classified as
      ganglioneuroblastoma. Since this nosological entity, unlike MPNST, cannot be
      assigned to a group of sarcomatoid tumors, the described pathology should be
      regarded as the first registered case of neuroectodermal histogenesis of tumors
      in reptiles.

PMID- 16986501
TI  - [Is atherosclerosis a specific arterial lesion or a "unified" group definition?
      Search for the causes of arteriosclerosis: an ecologic conception].
AB  - The term "atherosclerosis" is erroneously used for the definition of different
      types of arteriosclerosis, each of them has not only its characteristic
      structural signs, but also its specific causes and the mechanisms of its
      development. Particularly, young subjects are observed to mainly have lipid-free
      arterial intimal lesion with formed myofibrous, fibrous hyalinized plaques, and
      circular or focal myoelastic intimal hyperplasia. This type of atherosclerosis
      more commonly occurs in those who are occupationally exposed to xenobiotics. The
      establishment of the actual cause of each type of arteriosclerosis will open up
      fresh opportunities for the prevention of the diseases that are responsible for
      high morbidity and disability rates in the past decades.

PMID- 16986502
TI  - [Thyroid microcarcinoma].
AB  - The WHO classification of thyroid tumors defines papillary microcarcinoma as
      papillary carcinoma, 1 cm or less in diameter. Many Russian and foreign authors
      include follicular and medullary types. The limiting size which permits a tumor
      to be considered microcarcinoma if it measures either 1 cm or 1.5 cm. A number of
      investigators terminologically use the data of a clinical observation of
      patients. In this connection, there is a great variety of terms used to define
      thyroid microcarcinoma. This tumor is a common random finding in the gland
      removed for various disease or examined at autopsy. According to autopsies, the
      incidence of thyroid microcarcinoma ranges from 1 to 36%. A great deal of papers
      and studies are dedicated to the etiology and pathogenesis of thyroid
      microcarcinoma and the potentialities of its early diagnosis and adequate
      treatment. However, little attention is given to the histological structure and
      proliferative activity of this tumor and their impact on prognosis and data are
      at times slightly contradictory or inadequately complete.

PMID- 16986503
TI  - [Arterial fibromuscular dysplasia].
AB  - The paper reviews the data available in the literature on the etiology,
      pathogenesis, pathomorphology and examinations of patients with fibromuscular
      dysplasia. The types of fibromuscular dysplasia are discussed in detail in
      relation to the damage to vascular wall layers. These include intimal
      fibroplasia, medial hyperplasia, medial fibroplasias, and perimedial fibroplasia
      with a well-defined definition pathomorphological and angiographic criteria. The
      role of various etiological factors in the development of fibromuscular dysplasia
      is given, by presenting the genetical, mechanical, ishemic, humoral, and hormonal
      hypothesis of pathogenesis; differential diagnostic features are determined.
      Emphasis is laid on the necessity and topicality of studying the etiology,
      pathogenesis, and pathomorphology of dysplasia to gain a better insight into this
      disease, to choose an effective treatment.

PMID- 16986504
TI  - [Association between methylenetetrahydrofolate reductase gene haplotypes and the
      susceptibility of chromosomal damage in coke-oven workers].
AB  - OBJECTIVE: To investigate the association between MTHFR gene variances and
      chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers
      exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: One-hundred and
      forty coke-oven workers who exposed to a high level of PAHs and sixty-six non
      exposed controls were selected as the study subjects. Chromosomal damage in
      peripheral lymphocyte was measured by the cytokinesis-block micronucleus (CBMN)
      assay. Urinary 1-hydroxypyrene (1-OHP) levels were measured as the internal dose
      of PAHs exposure. Two single nucleotide polymorphisms(SNPs) in MTHFR gene,
      including C677T, A1298C were detected by PCR-RFLP. The MTHFR haplotypes were
      estimated by Bayesian statistical method with the software of PHASE Version 2.1.
      The associations between haplotype pairs and CBMN were assessed by analysis of
      covariance in the coke-oven workers and controls. RESULTS: The variant allele
      frequencies for MTHFRC677T and A1298C were 0.56 and 0.16 respectively, which
      consistent with Hardy-Weinberg equilibrium. There was linkage disequilibrium
      between the two SNPs (D' = 0.99) in this study. Four haplotypes were calculated
      by PHASE, in terms of 677T - 1298A, 677C-1298A, 677C-1298C and 677T-1298C, the
      frequencies were 0.555,0.279,0.163 and 0.003 respectively. In coke-oven workers,
      the frequencies of total micronucleus of non-677C-1298A/677C-1298A haplotype pair
      was significantly higher than 677C-1298A/677C-1298A (1.00 +/- 0.67 vs 0.60 +/-
      0.41, P = 0.04). The frequencies of total micronucleus of 677T-1298A/677T-1298A
      haplotype pair was significantly higher than 677C-1298A/677C-1298A (1.08 +/- 0.71
      vs 0.60 +/- 0.41, P = 0.04). In coke-oven workers, the frequencies of total
      micronucleus among the different SNPs were not significant differences, either in
      the controls. CONCLUSION: The haplotypes of MTHFR gene might be one genetic
      susceptibility factors of PAH induced chromosomal damage in coke-oven workers.

PMID- 16986505
TI  - [Serum organochlorines pesticides level of non-occupational exposure women and
      risk of breast cancer:a case-control study].
AB  - OBJECTIVE: To describe exposure level of organochlorines pesticides residues in
      non-occupational exposure population in China and testify the hypothesis that
      organochlorine pesticides exposure may be the risk factor to human breast cancer.
      METHODS: A case-control study based on community was designed. 90 new diagnostic
      breast cancer patients from the Second Hospital of Sichuan Province, and 136
      health women from community, who settled down in the same district as case were
      enrolled. The risk factors of breast cancer were investigated by a questionnaire.
      GC-ECD was used to measure the serum level of Organochlorines pesticide residues.
      The adjusted odds rations (OR) of organochlorines pesticides residues to breast
      cancer were evaluated by logistic regression model. RESULTS: 8 organochlorines
      pesticide residues including p, p'-DDT, p, p'-DDE, o, p'-DDT, p, p'-DDD and
      alpha, beta, gamma, delta-HCHs (hexachlorocyclohexane) could be detected in serum
      of cases and controls. The detecting rates of beta-HCH, p, p'-DDE and p, p'-DDT
      respectively were 91.2%, 92.1% and 91.2%. There were no significant differences
      of serum level of organochlorines pesticides residues between cases and controls
      (P > 0.05). After adjusting confounding factors, serum p,p'-DDT, p,p'-DDD, and
      delta-HCH level were positively related to the risk of breast cancer (adjusted OR
      > 2, P < 0.05) . High serum p,p'-DDT,p,p'-DDD and beta-HCH level were positively
      correlated to premenopausal women (adjusted ORs respectively were 3.59, 5.70 and
      3.06, P < 0.05). CONCLUSION: Organochlorines pesticides resides, including DDTs
      and HCHs, may increase women's risk of breast cancer, particularly in
      premenopausal women in China.

PMID- 16986506
TI  - [Analyzing the function of different expression genes in the brain of rat
      exposure to methylmercury using genomics technology].
AB  - OBJECTIVE: Analyzing the function of different expression genes in the brain of
      rat exposure to methylmercury. METHODS: The experimental group of rats were
      treated with 0.5 mg/kg weight of methylmercury via hypodermic injection. The
      different expression genes were scanned by using cDNA microarray, and the
      function genes were analyzed using genomics technology. RESULTS: The gene
      expression profiles showed that there were 303 genes, in which 170 were
      upregulated and 133 were downregulated, were differential expressed in the
      experimental group. Further analysis by bioinformatic technique disclosed that
      the differentially expressed genes were involved in many biological processes,
      which included immuno-response and detoxifcation, transfer and expression of
      genetic information, cell signalling, neurotransduction, cell proliferation and
      cell differentiation, apoptosis, etc. Cell signaling gene and neurotransduction
      gene had an very obvious change in the exposure group. CONCLUSION: The signaling
      pathway was the target by which methylmercury exerted the neurotoxic effects.

PMID- 16986507
TI  - [Effects of styrene on the dopaminergic transmitter content and monoamine oxidase
      activity in different sections of rat brain].
AB  - OBJECTIVE: To observe the effect on dopaminergic transmitter content and of
      monoamine oxidase (MAO) activity at dose of experiment in different sections of
      rat brain exposed bu acutely and subacutely styrene. METHODS: Rats were
      administrated orally with styrene of at dose of 600mg/kg for acute, 150, 300 and
      600mg/kg for subacute experiment; recovery group were observed after 3 weeks
      exposure of styrene and intervened group were injected intraperitoneally at dose
      of 600mg/kg Levodopa (L-dopa) ; the urinary metabolites of styrene mandelic acid
      (MA) and phenylglyoxylic acid (PGA) were monitered as inner dosage, and the
      content of dopamine (DA) and activity of MAO were evaluated. RESULTS: The result
      indicated that the content of urinary MA and PGA were associated with dosage
      positively, and MA may be more sensitive as inner dosage of styrene exposure
      since the background of PGA. Levels of DA in retina, hypophysis and striatum were
      decreased after styrene exposure, the activities of MAO in hypophysis were
      increased and were reduced in retina and striatum. CONCLUSION: It was suggested
      dopaminergic system could be participated in styrene neurotoxicity.

PMID- 16986508
TI  - [Effects of perinatal exposure to methylmercury on the structure of hippocampus
      and cerebellum in young rats].
AB  - OBJECTIVE: To evaluate the effects of perinatal exposure to methylmercury on the
      structure of hippocampus and cerebellum in young pups. METHODS: Divided the 9
      pregnant SD rats into three groups randomly: group I, II and III After exposing
      the rats of the three groups from day 7 in pregnancy through lactation with
      methylmercury (the dose were 0, 0.1 and 1mg/(kg x d) respectively), examined the
      early physiology development and the structure of hippocampus and cerebellum of
      day-21-offspring rats. RESULTS: Except for changes in body weight on 21 day, the
      offspring showed no apparent changes in appearance and physiology. Pyknosis in
      several neurons and disturbance arrangement of pyramidal cells in CA3 and CA4
      region of the hippocampus were observed in hippocampus and cerebellum of the rats
      in group III under the microscope, while no pathological changes were observed in
      group II. Testing the positive expression of immunohistochemistry, we found out
      that the NF expression of hippocampus in II and III groups were lower than group
      I (F = 7.94, P < 0.01), while that of GFAP were increased significantly (F =
      10.10, P < 0.01). NF expression of cerebellum in group III was lower than group
      II and group I (F = 6.85, P < 0.05). while that of GFAP was higher than the other
      two groups (F = 6.85, P < 0.05). The ultrastructure changes happened in both II
      and III groups examined through electron microscope, including irregular form in
      nucleus of neurons, pyknosis of soma, degeneration of mitochondria, lysis of
      dendrite and axon, et al. CONCLUSION: Perinatal low-level methylmercury exposure
      affected the ultrastructure and expressions of the neural cells in cerebellum and
      hippocampus of the young rats.

PMID- 16986509
TI  - [Effect of Ligustrazine on type I, III collagen synthesis in lung tissue of
      silica-treated rat].
AB  - OBJECTIVE: To study the effect of Ligustrazine on type I, III collagen synthesis
      in lung tissue of silica-treated rat. METHODS: The 128 experimental rats were
      randomly divided into control, silica and Ligustrazine group. 1ml silica (50g/L)
      was injected intratracheally in silica group and Ligustrazine group, while
      Ligustrazine group were injected intraperitoneally 50mg/(kg x d) Ligustrazine.
      Samples were collected on the 1st, 3rd, 7th, 14th, 21st, 28th day after injected
      silica. Type I , III collagen on paraffin-embedded lung sections were stained
      with sirius red, detected by polarized light microscopy and quantified by Image
      Pro Plus. RESULTS: On the 3rd day after silica instillation, type III collagen
      began to appear, while type I collagen formed on the 7th day. Thereafter Type I,
      III collagen increased progressively. Compared with control group, type I, III
      collagen expression of silica group increased. At different time points type I,
      III collagen expression of Ligustrazine group decreased than silica group. There
      was significant difference of type I collagen area percentage on the 7th, 14th,
      28th day, type III collagen area percentage on the 28th day between Ligustrazine
      group and silica group. CONCLUSION: Silica dioxide could induce the increase of
      type I, III collagen production in lung tissue, and their stages are different.
      Ligustrazine could suppress type I, III collagen production in lung tissue of
      silica-treated rat, and it's mechanism would be studied.

PMID- 16986510
TI  - [Comparison of TK gene mutation assay in TK6 and TK6-E6 cell induced by
      vinblastin and colcemid].
AB  - OBJECTIVE: To compare TK gene mutation assay in human lymphoblastoid cell lines
      TK6 and TK6-E6 induced by vinblastin and colcemid. METHODS: Regular TK gene
      mutation assays were experimented to detect cytotoxicity and mutation frequency
      at tk locus after TK6 and TK6-E6 human lymphoblastoid cells were treated with
      vinblastin and colcemid for 24h. RESULTS: Relative survival (RS%) and Relative
      suspension growth (RSG%) of TK6 and TK6-E6 cells decreased when concentrations of
      vinblastin and colcemid increased. RS% and RSG% of TK6-E6 cells were higher than
      that of TK6 cells at the same doses. TK6 and TK6-E6 cells both were induced by
      vinblastin and colcemid. The TK6-E6's nature mutation frequency, induced mutation
      frequency and percentage of slow growth mutant (SG%) were lower than TK6' s at
      the same dose except group CCM 5.0ng/ml in MF and group CCM 0.625ng/ml in SC%.
      CONCLUSION: Both TK6 and TK6-E6 cell lines can be used in TK gene mutation assay,
      but TK6-E6 cell line was recommended to be used in the assay for its less
      quantity and doubling time.

PMID- 16986511
TI  - [Protective effect of reduced glutathione on cytotoxicity induced by hexavalent
      chromium [Cr(VI)] in L-02 hepatocyte].
AB  - OBJECTIVE: To explore the effect of reduced glutathione (GSH) on cytotoxicity
      induced by hexavalent chromium (Cr(VI)) in L-02 hepatocyte. METHODS: The test has
      three groups:the groups of (Cr(VI), the groups of GSH, the groups of Cr (VI) and
      GSH. The survival rate of L-02 hepatocyte is assessed on the reductions of
      tetrazolium dye (MTT). RESULTS: Significant cytotoxicities of L-02 hepatocyte
      were observed at the concenations of 2,4,8,16,32 and 64 micromol/L Cr (VI).
      Concentration-dependent decrease in cell survival rate of Cr (VI)-treated L-02
      hepatocytes were observed (r = -0.910) Protective effect on all concentrations of
      Cr(VI) (2 - 64 micromol/L) at the dose of 20 micromol/LGSH were found.
      CONCLUSION: The results demonstrated that proper concentrations of GSH could have
      protective effect on cytoxicity induced by Cr(VI) in L-02 hepatocyte. GSH of too
      low or too high concentrations don't has this effect.

PMID- 16986512
TI  - [Study of L-02 hepatocyte apoptosis induced by hexavalent chromium associated
      with mitochondria function damage].
AB  - OBJECTIVE: To explore the effect of hexavalent chromium on apoptosis of L-02
      hepatocytes and the functions of mitochondria. METHODS L-02 hepatocytes in all
      tests were incubated with 0,2,4,8,16,32 [see text] 64 micromol/L of Cr(VI) for
      6h. Apoptosis of L-02 hepatocytes in the presence of Cr(VI) was quantified by
      flow cytometry (FCM). The permeability transition pore (FTP) of mitochondria and
      mitochondrial membrane potential as indicators of mitochondrial damage were
      measured by fluorescent spectrometer. RESULTS: Concentration-dependent decrease
      in cell apoptosis rate of Cr(VI)-treated L-02 hepatocytes were observed. The
      results of permeability transition pore (PTP) of mitochondria, mitochondrial
      membrane potential in all concentrations of Cr(VI) had significant difference
      when compared to the control cells (P < 0.05). CONCLUSION: The results
      demonstrated that L-02 hepatocytes apoptosis induced by Cr(VI) associated with
      mitochondrial damages.

PMID- 16986513
TI  - [Study on bisphenol A induced primary cultured mesencephalic neuronal cell injury
      by oxidative stress].
AB  - OBJECTIVE: To investigate the effect and mechanism of bisphenol A, a common EDCs,
      on the primary cultured mesencephalic neuronal cell injury. METHODS:
      mesencephalic neuronal cells were obtained from embryonic 14-15 day SD fetuses
      and were cultured in serum free medium for 4 or 7 days in vitro, 1,10,25,50 and
      100 micromol/L bisphenol A were added to the medium and intracellular ROS, SOD,
      MDA, GSH were measured after 24 or 48hours, respectively. Flow cytometry was used
      to detect the neuronal cell apoptosis. Tyrosine hydroxylase immunohistochemistry
      was used to identity and count the ratio of dopaminergic neuronal cell. RESULTS:
      The intracellular ROS was dose dependently increased by bisphenol A in all
      treated groups, and it appeared to be a nonselective effect when the
      concentration of bisphenol A were higher than 50 micromol/L, and concomitantly
      decreased SOD, GSH and increased MDA. The apoptotic neuronal cells were
      significantly increased at 501 micromol/L and 100 micromol/L. The ratio of
      Tyrosine hydroxylase positive neuronal cell was dose dependently decreased with
      the concentration of bisphenol A. CONCLUSION: ROS induced by bisphenol A may play
      a major role in its cytotoxicity on dopaminergic neuronal cell.

PMID- 16986514
TI  - [Study on repair capacity of DNA damage associated with chronic benzene
      poisoning].
AB  - OBJECTIVE: To explore the repair capacity of DNA damage associated with chronic
      benzene poisonings. METHODS: 63 workers suffered from chronic benzene poisonings
      and 45 workers exposed to benzene, who were engaged in the same job title, were
      investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection
      were used to evaluate gamma-radiation-induced DNA and chromosomal damage and
      repair capacity in peripheral blood lymphocyte. RESULTS: The comet tail length
      difference of the benzene poisoning group (4.64 +/- 1.57 microm) was
      significantly higher than that of the control group (3.77 +/- 1.30 microm) (P =
      0.0029). There was no significant difference of the 3AB index between the
      poisoning group and the control group. The relative risk of benzene poisoning in
      the subject with comet tail length difference > 3.81 was significantly higher
      than that in the subject with comet tail length difference < or = 3.81 microm (OR
      = 2.490, 95% CI:1.068 - 5.806, P = 0.0346). The relative risk increased along
      with the comet tail length difference, and the trend was significant (P =
      0.0024). There was no significant difference between the relative risk of benzene
      poisoning in the subject with 3AB index < 0.20 and that in the subject with 3AB
      index > or = 0.20. CONCLUSION: DNA repair capacity on DNA-strand level might
      tightly associate with chronic benzene poisoning. The DNA repair capacity on DNA
      strand level would be worse, and the benzene poisoning risk could be higher.
      There was no clear relation between the DNA repair capacity on chromosome level
      and the benzene poisoning risk.

PMID- 16986515
TI  - [Effect of zinc on mRNA expression of ZIP4 in Caco2 cells].
AB  - OBJECTIVE: To study the effect of zinc on mRNA expression of ZIP4 in human
      intestinal Caco2 cells and its regularity. METHODS: Low zinc cell model was
      established by TPEN, a kind of chelating agent which chelates specially to zinc.
      ZIP4 cDNA fragment was obtained by RT-PCR. Expression of ZIP4 on 10 micromol/L
      TPEN exposure after 0, 2, 4, 6, 8 and 10 hours in Caco2 cells and its expression
      on various concentration of TPEN exposure (0,2.5,5,7.5 and 10 micromol/L) was
      measured by RT-PCR. RESULTS: A proper single fragment is obtained with the
      sequence conformable to the design. A proper single ZIP4 cDNA fragment was
      obtained. The mRNA expression of ZIP4 increased in accordance with the duration
      of low zinc. The peak mRNA level appeared at about 6h. And the ZIP4 mRNA
      increased in accordance with the concentration of TPEN in Caco2 cells.
      CONCLUSION: Zinc can regulate the mRNA expression of ZIP4 in Caco2 cells. And
      ZIP4 may play a role in the absorption of zinc in human intestine.

PMID- 16986516
TI  - [Alcohol inhibited the expression of glial fibral acidic protein and S100 of
      astrocytes].
AB  - OBJECTIVE: To explore effects of alcohol on the expression of gial fibral acidic
      protein (GFAP) and S100 of astrocytes in brain. METHODS: Different dosages of
      alcohol (2,5 and 20 mmol/L) were administered to astrocytes of fetal rat brain in
      vitro. The expression of GFAP and S100 of astrocytes was detected by
      immunocytochemistry, respectively. RESULTS: With the dosage of alcohol
      increasing, the expression of GFAP and S100 was reduced and the number of
      astrocytes in high dosage group was observed to be decreased slightly.
      CONCLUSION: It suggested that alcohol could repress the expression of GFAP and
      S100 of astrocytes, which might be the main mechanism of developmental
      abnormalities of central nervous system induced by alcohol.

PMID- 16986518
TI  - [Analysis of paralytic shellfish poisoning and diarrhetic shellfish poisoning of
      bivalves in seafood market of Guangzhou].
AB  - OBJECTIVE: Paralytic shellfish poisoning (PSP) and diarrhetic shellfish poisoning
      (DSP) in 7 species of economical shellfishes were analyzed for 1 year, which
      collected from Huangsha seafood market of Guangzhou from Apr, 2004 to Mar, 2005.
      METHODS: The levels of PSP and DSP in bivalves were determined with mouse
      bioassay of AOAC. The risk assessment of PSP and DSP in bivalves was conducted
      according to FAO and Chinese Administration Organization of Fish Culture and
      Seaport. RESULTS: PSP was detected in 2 species of the shellfishes assayed and
      DSP was found out in 6 species. The content of PSP was lower than 4MU/g tissue,
      whereas the level of PSP in glands was higher than in muscles. DSP toxin was
      detected in 36 samples of 6 species, what is more, DSP level in 10 samples
      exceeded the safety threshold. The levels in PSP and DSP of bivalves were all
      higher in spring and winter with some characteristic of season. CONCLUSION: The
      results suggested that PSP in economical shellfish in Guangzhou market was lower,
      and shellfish was safe to eat in term of the PSP level if glands were discarded,
      but DSP contamination in bivalves was severe. It is essential to detect and
      assess the risk of DSP and PSP in bivalves from seafood market in the future.

PMID- 16986517
TI  - [Stability of hpt marker gene in transgenic rice in different food matrices and
      under varying food-processing conditions].
AB  - OBJECTIVE: To estimate the likelihood of horizontal gene transfer from transgenic
      rice to bacteria of the food chain and human gut, the stability of s86 transgenic
      rice hpt gene in different food matrices and under varying food-processing
      conditions was studied. METHODS: Degradation of DNA was monitored by fragment 
      multiplex polymerase chain reaction. Integrity of hpt gene in various food
      samples was tested. RESULTS: A PCR system for the hpt gene of genetically
      modified rice has been established to detect fragments ranging between 236bp and
      910bp. Detection of hpt and rbcl gene fragments was carried out in various food
      processed samples by this PCR system. The data showed that the fragments up to
      500 bp were detected in rice and congee, while the fragment length more than
      236bp was not detected in crispy rice and popcorn-like rice. CONCLUSION: These
      results suggested that there are significant differences in DNA degradation by
      different food-processing methods. The likelihood of the large hpt gene fragments
      transfer from transgenic rice processed food to bacteria is reduced by food
      process.

PMID- 16986519
TI  - [Development of a gold-immunochromatography test for rapid detecting E. coli
      O157].
AB  - OBJECTIVE: To develop a method for rapid detecting Escherichia coli (E. coli)
      O157 on site. METHODS: A colloidal gold immunochromatography test based on double
      antibody sandwich assay for detecting E. coli O157 was developed. Its sensitivity
      and specificity were then evaluated, and its feasibility of screening food
      samples were evaluated by analyzing various samples added with E. coli O157.
      RESULTS: Typical detecting time is less than 15 minutes per sample. The
      sensitivity of the test is 1 x 10(5) cfu/ml. No any cross-reaction with 30
      strains of 24 species in Enterobacteriaceae (including non-O157 E. coli,
      Salmonella, Shigella, Proteus, Citrobacter, Enterobacter, Serratia and Yersinia),
      Staphylococus, Listeria, Aeromonas and Vibrios was found. The test could be used
      to detect E. coli O157 in various samples such as milk powder, flour, starch,
      coffee, biscuit, cake, jelly and juice. CONCLUSION: The gold-immunochromatography
      test appears to be a rapid, convenient, specific and sensitive test for detecting
      E. coli O157: H7 on site.

PMID- 16986520
TI  - [Production and characterization of gold labeled monoclonal antibody against MC
      LR].
AB  - OBJECTIVE: Production of the gold labeled monoclonal antibody against MC-LR.
      Study the simple mechanism of the conjugation by the spectral analysis. METHODS:
      Production and purification monoclonal antibodies against MC-LR by hybridoma
      technology. Production the 20nm colloidal gold and label the monoclonal antibody.
      Study the gold--McAb conjugate by the spectroanalysis. RESULTS: Monoclonal
      antibody produced by the hybridoma cells were tested for subtypes and designated
      as IgG2a for 8C11. The titers of antibody in ascites was 108.The IC50 for MC-LR
      was around 3ng/ml. The IgG molecule weight was 1.5 x 10(5). The structure of the
      antibody was altered to more tighter and stabler. CONCLUSION: Product the gold
      labeled monoclonalantibody against MC-LR conjugate successfully and keep the
      antige-binding determinant.

PMID- 16986521
TI  - [Association of gene polymorphism at cholesterol ester transfer protein locus
      with obesity and response to dietary intervention in obesity].
AB  - OBJECTIVE: To study the association of gene polymorphism at cholesterol ester
      transfer protein (CETP) locus with obesity and response to dietary intervention
      in obesity. METHODS: The PCR-PFLP method was used to detect the polymorphism of
      CETP gene of 340 adults in Shanghai. The levels of serum lipid profile, including
      TG, TC, HDL and LDL were analyzed. Obesity was selected to dietary intervention.
      RESULTS: (1)The genotype frequencies of CETP-TaqIB B1 B1, B1 B2 and B2 B2 were
      35.6%, 47.9% and 16.5% respectively, which were in agreement with Hardy-Weinberg
      equilibrium. There was no significant difference in the distribution of genotypes
      between the obesity group and control group. The result was same after several
      influence factors controlled. (2) The levels of HDL were significantly different
      among genotype groups. Subjects for the B2 B2 genotype had the highest HDL
      levels. The relationship was steady after adjusting several influence factors.
      (3)Subjects for the B1 B2 genotype had higher HDL level after intervention, which
      was significantly different to other genotype groups. After adjusting baseline
      HDL level and gender, genotype didn't effect the change in HDL. CONCLUSION: CETP
      TaqIB gene polymorphism influenced serum HDL level. But this gene polymorphism at
      CETP locus wasn't especial in adult obesity. Baseline HDL level influenced the
      change in HDL response to dietary intervention in three genotype groups.

PMID- 16986522
TI  - [Analysis of the nutrients contents and the blood glucose response of the mixed
      grains in Chinese people].
AB  - OBJECTIVE: To evaluate the nutrients contents and the glycemic index (GI) of the
      mixed grains and analyze the relationship between the nutrients contents and
      biological effect. METHODS: The nutrients contents of mixed grains and control
      food were determined according to the methods of Chinese national standards.
      Choose 10 volunteers to ingest 50 g glucose and ingest the steamed bread of mixed
      grains which imply 50 g carbohydrate the second day. Limosis blood glucose and
      blood glucose levels during the subsequent 3 hours were determined. Calculating
      the GI according to the Wolver's method. RESULTS: The results showed that 100 g
      of the mixed grains contained dietary fiber (crude fiber) 13.7 g, vitamin B1 0.40
      mg, protein 13.5g, ash2.0g, vitamin B2 0.16 mg, calcium 54 mg, iron 7.1 mg and
      zinc3.00 mg respectively. The absolute increase of blood glucose and the areas
      increased under the glycemic curves of mixed grains were less than which of
      glucose (P < 0.05). The GI of the mixed grains bread was 52.6. CONCLUSION: It was
      concluded that the high contents of protein, minerals, dietary fiber, VB1, VB2
      and the low GI of mixed grains might play an important role in nutritional
      intervention

PMID- 16986523
TI  - [Analysis of the concentration of plasma copper and collagen in fetal membrane of
      the preterm's mothers].
AB  - OBJECTIVE: The purpose of the study is to determine primarily the concentration
      of plasma copper and collagen in fetal membrane of the preterm's mothers, and
      explore the relation of copper status and fetal membrane collagen of preterm's
      mothers. METHODS: The general situations were collected both in neonatos and
      their mothers. The plasma copper concentrations of mother venous blood and cord
      blood were analyzed by ICP-OES. Sirius Red dyeing was first used in fetal
      membrane to detect the thickness and collagen in preterm's and full-term's
      mothers. RESULTS: The prevalence of premature rupture of membrane (PROM) was
      40.00% in preterm's mothers, and 9.09% in the full-term's mothers. The mothers'
      preconceptual weight, infant body length and body weight at birth were lower in
      preterm group than those of the full-term group. The cord blood plasma copper was
      significantly lower in preterms than in full-terms. Both the thickness and the
      concentration of collagen I and II of non-split fetal membrane of preterm's
      mothers were significantly less than those of the full-term's mothers.
      CONCLUSION: Both the concentration of plasma copper and fetal membrane collagen
      of preterm's mothers were lower than that of the full-term's. It can confer that
      the deficient copper status could lead to immature collagen in fetal membrane
      which induce PROM and have preterm birth finally. More work need to be done in
      this field.

PMID- 16986524
TI  - [Study on the baseline contents and reference maximum limit standard of heavy
      metals and harmful element of 23 Chinese herbs in Northern China].
AB  - OBJECTIVE: This study was carried out to obtain the baseline contents and
      establish the reference maximum limits of heavy metals and harmful element in
      China. METHODS: According as Chinese standard methods of heavy metals and harmful
      element, 254 Chinese herbs were determined. RESULTS: The contents of lead,
      cadmium, mercury and arsenic in different Chinese herbs were (1.78 +/- 1.98),
      (0.17 +/- 0.24), (0.04 +/- 0.06) and (0.72 +/- 0.69)mg/kg, respectively. In the
      process of establishing the reference maximum limit standards of these harmful
      substances, the dietary intakes which including the intakes from food, beverage
      and drinking water were necessarily considered. The intakes including dietary and
      Chinese herbs of per person per day (and the percent of ADI) of lead, cadmium,
      mercury and inorganic arsenic were 102.9 microg (45.7%), 21.4 microg (34.0%), 5.7
      microg (5.7%) and 81.0 microg (60.5%), respectively. We recommended the reference
      maximum limit standards of lead, cadmium, mercury and arsenic which in Chinese
      herbs were 5.0 mg/kg, 0.3 mg/kg, 0.2 mg/kg and 2.0 mg/kg, respectively.
      CONCLUSION: The survey of baseline level of heavy metals and harmful element was
      successful. The intakes of these harmful substances were safe to human health.
      The maximum level standards of lead, cadmium, mercury, arsenic in plant Chinese
      herbs submitted by our coordinated group have been accepted by Chinese Herbs
      Codex, 2005 version. This standard is suitable for quality standards in plant
      Chinese herbs.

PMID- 16986525
TI  - [A case-control study of the risk factors for lung cancer among Chinese women who
      have never smoked].
AB  - OBJECTIVE: To investigate the risk factors for lung cancer among women who had
      never smoked. Methods A 1:2 matched case-control study was carried out. The cases
      are the no-smoking female patients with the primary lung cancer diagnosed by
      pathology mothed from hospitals in Beijing, Shanghai and Chengdu between
      September 2001 and February 2004. One hospital control and one population control
      matched for age, sex and no-smoking et al., were enrolled. The case and control
      were interviewed about the exposure information of related factors using the
      uniform questionnaire. Statistical analysis of single-factor and multivariate
      conditional Logistic regression were performed to screen the risk factors of lung
      cancer. RESULTS: During the single-factoranalysis, 28 exposure factors were
      identified as risk factors for lung cancer. The multivariate conditional Logistic
      regression show that passive smoking index > or = 50 person * year (OR = 1.77,95%
      CI, 1.07 - 2.92), consumption of internal organs of animals (OR = 1.85,95% CI,
      1.06 - 3.22), and occupational exposure to dust (OR = 2.47,95% CI, 1.21 - 5.03)
      and bad ventilation in workplace( OR = 4.02,95% CI, 1.74 - 9.29) are risk factors
      for lung cancer, but consumption of vegetables( OR = 0.26, 95% CI, 0.12 - 0.59),
      taking vitamins often (OR = 0.53, 95% CI, 0.30 - 0.93), average month income per
      person after married > or = 500 yuan ( OR = 0.50, 95% CI, 0.28 - 0.91) and the
      first procreation occurred between 24 and 30 years old (OR = 0.53, 95% CI, 0.32 -
      0.90) are the protective factors for lung cancer. The dose-response were observed
      between passive smoking and risk rate of lung cancer by trend test. CONCLUSION:
      Some factors such as passive smoking, consumption of internal organs of animals,
      occupational exposure to dust and bad ventilation in workplace can increase the
      risk of lung cancer for women who had never smoked. Other factors such as
      consumption of vegetables, taking vitamins, and so on, can reduce the risk of
      lung cancer for women who had never smoked.

PMID- 16986526
TI  - [Study on the level changes of obesity-associated factors and puberty-associated
      hormones and their relationship between obese and normal 13 years old children].
AB  - OBJECTIVE: To investigate the level changes of obesity-associated factors and
      puberty-associated hormones and their relationship between obese and normal
      Children. METHODS: The concentrations of orexins, leptin, insulin, testosterone
      (T), estradiol (E), luteotrophic hormone (LH), as well as follicle stimulating
      hormone (FSH) in blood were measured respectively in 78 cases of 13 years old
      obesity children and 84 normal children as a control group by the means of RIA
      methods. The bone ages were evaluated with "bone age standard of hundred percent
      scale". RESULTS: The leptin and insulin concentrations were significantly higher
      in obesity children as compared with the control group (P < 0.01). The
      concentrations of plasma orexinA were significantly lower in obesity children as
      compared with the control group (P < 0.01). The concentrations of T were
      significantly lower in obesity boys as compared with the control group (P <
      0.01). The concentrations of E2 and LH were significantly higher in obesity girls
      as compared with the control group (P < 0.01). The bone age of the obese children
      was significantly older than that of the control group. Along with the bone age
      of children became older, the concentration of leptin and LH in blood were
      significantly increased. There was a positive correlation between LH and FSH in
      two groups of either boys and girls and so did between leptin and insulin, C
      peptide, E2 (P < 0.01). In the group of normal boys, the positive correlations
      between LH, FSH and E2 were shown (r = 0.373, 0.314, P <0.05), and a negative
      correlations between leptin and T were shown as( r = -0.423, P < 0.01), a
      positive correlation between leptin and FSH was also shown as (r = 0.308, P <
      0.05). In the control group of girls, there were positive correlations between
      leptin, LH and E2 (r = 0.585, 0.647, P < 0.01). Any correlations between LH, FSH
      T and E2 were not shown in the two obese groups of boys and girls. CONCLUSION:
      The leptin, orexinA, insulin, T, E2, and LH concentrations had been changed
      significantly in blood among those obesity children, and so as their
      interactions. The high level of leptin in obesity children may change the
      concentrations of T, E2 and LH and affect the development of puberty.

PMID- 16986527
TI  - [Study on the relationship between workplace violence and work ability among
      health care professionals in Shangqiu City].
AB  - OBJECTIVE: To study the relationship between workplace violence and work ability
      and to provide evidence for preventing workplace violence and improving work
      ability among health care professionals. METHODS: A test of the workplace
      violence and work ability was carried out with workplace violence scale and work
      ability index, and Other information was investigated with questionnaire among
      507 health care professionals in Shangqiu City of China. RESULTS: (1) The mean
      score of workplace violence was significantly higher in the group aged 30 - 44
      than that of the group aged 45 - 59 (P < 0.05). (2) Among nurse group the mean
      score of workplace violence was higher than that of the doctor group and medical
      technician group (P < 0.05). (3) The mean score of WAI was lower in the group
      with primary educational level than that of other group (P < 0.05). (4) The
      workplace violence score correlated negatively to the WAI score (r = - 0.250, P <
      0.01). (5) Logistic regression analysis showed that after controlling the other
      risk factors, workplace violence was an important risk factor of work ability (
      OR = 8.44). CONCLUSION: Workplace violence has impact on work ability among
      health care professionals. Intervention measures should be taken to prevent
      workplace violence among health care professionals.

PMID- 16986528
TI  - [Study of the occupational stress norm and it's application for the executive
      group and administrative support group].
AB  - OBJECTIVE: A study of the occupational stress norm and it's application for the
      executive group and administrative support group. METHODS: In this study, cross
      sectional study method is used, and a synthetic way of sorting and randomized
      sampling is adopted to deal with research targets (263 executive group, 569
      administrative support group). RESULTS: Descriptive statistics for OSI-R scale
      scores for the executive group, administrative support group were modulated.
      Scale raw score to T-score conversion tables derived from the OSI-R normative
      sample for executive group, administrative support group were established. OSI-R
      profile from for executive group, administrative support group were established.
      For the ORQ and PSQ scales, scores at or above 70 indicate a strong levels of
      maladaptive stress and strain. Score inthe range of 60 to 69 suggest middle
      levels of maladaptive stress and strain. Score in the range of 40 to 59 indicate
      normal levels of stress and strain. Score below 40 indicate a relative absence of
      occupational stress and strain. For the PRQ scales, score below 30 indicate a
      significant lack of coping resources. Score in the range of 30 to 39 suggest
      middle deficits in coping resources. Score in the range of 40 to 59 indicate
      average coping resources. Scores at or above 60 indicate a strong levels of
      coping resources. CONCLUSION: Based on occupational Stress norm, raw score to T
      score conversion tables, OSI-R profile form and classification criterion, we
      could estimate the level of occupation stress, stressor, strain and coping
      resources in different occupation. In addition, we combined subjective and
      objective environment match model of occupational stress. The various individual
      and organizational intervention measures should be taken to reduce the
      occupational stress and to increase coping so as to improve the work ability.

PMID- 16986529
TI  - [Analysis and spatial description to correlative factors on food hygiene appeal
      and food poison in restaurants of city zone in Qingdao].
AB  - OBJECTIVE: To study some factors that affected food poison and appeals in
      restaurants which were hidden danger on the cards. METHODS: Data on food hygiene
      events from 2002 to 2004 in restaurants of 14 blocks which were located in the
      important city zone of Qingdao were collected and studied. The spatial
      distribution was conducted by means of Geographic Information System (GIS).
      Possible factors related to food hygiene events were investigated and analysed by
      NCSS Data statistics software. information of every block were marked on
      digitalized map by ARCVIEW3.2a software in order to show the spatial distribution
      of food hygiene events palpably in different areas in the course of three years.
      RESULTS: It was showed that air temperature, humidity, sunlight length were the
      important factors of food poison. Average amount of guests and floating
      population related to administration level of sanitation, the level of sanitation
      administration, geography location, business status of restaurants related to
      their status of food sanitation. CONCLUSION: This study showed the method that
      analysed and studied status of food sanitation from different areas by GIS were
      effective, simple and palpable.

PMID- 16986530
TI  - [Determination of total sulfur in coal by ion chromatography].
AB  - OBJECTIVE: To develop a method for determination of total sulfur in coal by ion
      chromatography. METHODS: To pretreat the coal by high-temperature combustion with
      oxygen-flow in tube furnace, and the sulfur with any from in coal was oxidated
      and converted into oxid of sulfur, which became sulfate after oxidated by H2O2
      absorption solution. The separation of sulfate was achieved on DionexAS12A anion
      exchange column with a carbonate eluent, and the detection is performed by the
      suppressed conductivity detector with the injection volume of 50 microl. The
      total sulfur in coals were obtained from the determined results. RESULTS: The
      method had been compared with the National Standard Method "High-Temperature
      Combustion--Neutralization Method for Determination of Total Sulfur in Coal
      (GB/T214-1996)", and the RSD of the method was less than 2% . This method had
      good relativity of the linearity (r = 0.9998) at the range of 0 to approximately
      15 microg/ml for sulfate. Two kinds of national certified reference materials
      (GBW11104c and GBWl1110d) were determined, and the RSD were 1.92% and 0.47%
      respectively. CONCLUSION: Ion chromatography for determination of total sulfur in
      coal has simple operation, high accuracy, and fast analysis, and can be applied
      in determination of total sulfur in coal.

PMID- 16986531
TI  - [Evaluation on analysis of six minerals in ten biologic materials].
AB  - The study is to evaluate the content of Mn, Cu, Fe, Zn, Mg and Ca in 10 sorts of
      biological material. The standard methods (GB/T5009.13,14,90,92 - 2003) were
      taken to measure. Two standard reference materials were used to control the
      accuracy of analyses. And chemical uncertainty was used to evaluate 6 minerals
      content. The results described the six minerals contents for the ten biologic
      materials. The study provided the necessity conditions to be used as standard
      reference materials for these 10 biological materials.

PMID- 16986532
TI  - [Comparison between rapid detection method of enzyme substrate technique and
      multiple-tube fermentation technique in water coliform bacteria detection].
AB  - OBJECTIVE: To compare between rapid detection method of enzyme substrate
      technique and multiple-tube fermentation technique in water coliform bacteria
      detection. METHODS: Using inoculated and real water samples to compare the
      equivalence and false positive rate between two methods. RESULTS: Results
      demonstrate that enzyme substrate technique shows equivalence with multiple-tube
      fermentation technique (P = 0.059), false positive rate between the two methods
      has no statistical difference. CONCLUSION: It is suggested that enzyme substrate
      technique can be used as a standard method for water microbiological safety
      evaluation.

PMID- 16986533
TI  - [Contrast analysis on two air fluorine content measurement methods].
AB  - OBJECTIVE: To take the two kinds of sampling and measurement methods of air
      fluorine content in the endemic fluorosis area to carry on the comparison,
      understanding their difference and inside relation. METHODS: Sampled 22
      households random on the scene in the disease area with two samplers by two
      methods, at the position of which, at the same time, equidistance, same highness,
      as close as possible, but not produce interactive effect, to collect 34 of the
      air sample, and then gained the results by their respective methods of laboratory
      analysis and statistical analysis. RESULTS: The test of significance between two
      methods was P > 0.05, the coefficient of correlation was r = 0.7752, the test of
      significance was P < 0.01, the equation of linear regression between the GB
      method (X) and the manual method (Y) was Y = 1.1623X + 0.0008, the test of
      significance of coefficient of regression was P < 0.01. CONCLUSION: Two kinds of
      methods had no significant differences. They preset the medium degree positive
      correlation and a linear regression. The air fluoride in different granularity of
      suspended particles was not the same. The GB method was more applicable to
      research of synthesis damage towards the exposing crowd in burning coal fluorine,
      and manual method was more applicable to research of the damage resulting from
      the exposing crowd in burning coal fluorine through the breath system. Generally
      speaking, the results of the manual method was higher than the GB method.

PMID- 16986534
TI  - [Determination of volatile organic compounds in drinking water by purge and trap
      gas chromatography/mass spectrometry].
AB  - OBJECTIVE: To establish a method for determination of volatile organic compounds
      in drinking water by purge and trap GC/MS. METHODS: Volatile organic compounds in
      water were purged and trapped by Tekmar 3100, then desorbed and analyzed by
      GC/MS. Selective ion masses were used in quantitative measurement. RESULTS: 60
      VOCs were separated and analyzed in 36 min. Within concentration range from 0
      microg/L to 12 microg/L, the correlation coefficient for 51 target compounds was
      greater than 0.995. The method detection Limits were in the range from 0.021
      microg/L to 0.70 microg/L. Recoveries were between 90% and 120%. RF RSD was less
      than 30%. CONCLUSION: Purge and trap gas chromatography/ mass spectrometry is a
      sensitive and accurate method for determination of volatile organic compounds in
      drinking water.

PMID- 16986535
TI  - [Toxicity study for acrylamide].
AB  - Acrylamide is one of the most important chemical materials, which has been widely
      used in industry. It is one kind of many contaminants in occupational
      environments. However, it has been reported that starchy foods cooked at high
      temperature contain a certain amount of acrylamide. The main acrylamide exposure
      route for non-professional population is intaking of high-temperature starchy
      foods. In this review, the studies for tumorogenesity, neurotoxicity,
      reproductive and developmental toxicity possibly caused by acrylamide were
      reported.

PMID- 16986536
TI  - [Analytical methods for the determination of acrylamide in food products].
AB  - In April 2002, researchers in Swedish reported that they had found high level
      acrylamide (AA) in carbohydrate-rich foods during cooking at high temperature,
      which shocked scientists worldwide. Because AA has been identified as being
      carcinogenic, neurotoxic and genotoxic, researchers had developed methods to
      determinate the AA level in kinds of foods. The review is based on the
      achievement and progress of AA analysis in foods in recent years which contains
      the samples' extraction, clean-up, derivatization and determination by
      chromatography coupled with mass spectrometer.

PMID- 16986537
TI  - [Radiation from mobile phone and the health].
AB  - With the development of the mobile communication industry, there are considerable
      public concerns about the relationship between mobile phone radiations and human
      health. With regard to electromagnetic field emitted by mobile phone maybe
      influence tumor,learning and memory, subjective symptoms and blood-brain barrier,
      a large number of studies have been performed abroad. This paper reviews the
      research development abroad on these problems, and analysizes the mechanism,
      through which the mobile phone effects on human health.

PMID- 16986538
TI  - Estimation of nonlinear errors-in-variables models for computer vision
      applications.
AB  - In an errors-in-variables (EIV) model, all the measurements are corrupted by
      noise. The class of EIV models with constraints separable into the product of two
      nonlinear functions, one solely in the variables and one solely in the
      parameters, is general enough to represent most computer vision problems. We show
      that the estimation of such nonlinear EIV models can be reduced to iteratively
      estimating a linear model having point dependent, i.e., heteroscedastic, noise
      process. Particular cases of the proposed heteroscedastic errors-in-variables
      (HEIV) estimator are related to other techniques described in the vision
      literature: the Sampson method, renormalization, and the fundamental numerical
      scheme. In a wide variety of tasks, the HEIV estimator exhibits the same, or
      superior, performance as these techniques and has a weaker dependence on the
      quality of the initial solution than the Levenberg-Marquardt method, the standard
      approach toward estimating nonlinear models.

PMID- 16986539
TI  - Activity recognition of assembly tasks using body-worn microphones and
      accelerometers.
AB  - In order to provide relevant information to mobile users, such as workers
      engaging in the manual tasks of maintenance and assembly, a wearable computer
      requires information about the user's specific activities. This work focuses on
      the recognition of activities that are characterized by a hand motion and an
      accompanying sound. Suitable activities can be found in assembly and maintenance
      work. Here, we provide an initial exploration into the problem domain of
      continuous activity recognition using on-body sensing. We use a mock "wood
      workshop" assembly task to ground our investigation. We describe a method for the
      continuous recognition of activities (sawing, hammering, filing, drilling,
      grinding, sanding, opening a drawer, tightening a vise, and turning a
      screwdriver) using microphones and three-axis accelerometers mounted at two
      positions on the user's arms. Potentially "interesting" activities are segmented
      from continuous streams of data using an analysis of the sound intensity detected
      at the two different locations. Activity classification is then performed on
      these detected segments using linear discriminant analysis (LDA) on the sound
      channel and hidden Markov models (HMMs) on the acceleration data. Four different
      methods at classifier fusion are compared for improving these classifications.
      Using user-dependent training, we obtain continuous average recall and precision
      rates (for positive activities) of 78 percent and 74 percent, respectively. Using
      user-independent training (leave-one-out across five users), we obtain recall
      rates of 66 percent and precision rates of 63 percent. In isolation, these
      activities were recognized with accuracies of 98 percent, 87 percent, and 95
      percent for the user-dependent, user-independent, and user-adapted cases,
      respectively.

PMID- 16986540
TI  - Convergent tree-reweighted message passing for energy minimization.
AB  - Algorithms for discrete energy minimization are of fundamental importance in
      computer vision. In this paper, we focus on the recent technique proposed by
      Wainwright et al. [33]--tree-reweighted max-product message passing (TRW). It was
      inspired by the problem of maximizing a lower bound on the energy. However, the
      algorithm is not guaranteed to increase this bound--it may actually go down. In
      addition, TRW does not always converge. We develop a modification of this
      algorithm which we call sequential tree-reweighted message passing. Its main
      property is that the bound is guaranteed not to decrease. We also give a weak
      tree agreement condition which characterizes local maxima of the bound with
      respect to TRW algorithms. We prove that our algorithm has a limit point that
      achieves weak tree agreement. Finally, we show that, our algorithm requires half
      as much memory as traditional message passing approaches. Experimental results
      demonstrate that on certain synthetic and real problems, our algorithm
      outperforms both the ordinary belief propagation and tree-reweighted algorithm in
      [33]. In addition, on stereo problems with Potts interactions, we obtain a lower
      energy than graph cuts.

PMID- 16986541
TI  - Three-dimensional model-based object recognition and segmentation in cluttered
      scenes.
AB  - Viewpoint independent recognition of free-form objects and their segmentation in
      the presence of clutter and occlusions is a challenging task. We present a novel
      3D model-based algorithm which performs this task automatically and efficiently.
      A 3D model of an object is automatically constructed offline from its multiple
      unordered range images (views). These views are converted into multidimensional
      table representations (which we refer to as tensors). Correspondences are
      automatically established between these views by simultaneously matching the
      tensors of a view with those of the remaining views using a hash table-based
      voting scheme. This results in a graph of relative transformations used to
      register the views before they are integrated into a seamless 3D model. These
      models and their tensor representations constitute the model library. During
      online recognition, a tensor from the scene is simultaneously matched with those
      in the library by casting votes. Similarity measures are calculated for the model
      tensors which receive the most votes. The model with the highest similarity is
      transformed to the scene and, if it aligns accurately with an object in the
      scene, that object is declared as recognized and is segmented. This process is
      repeated until the scene is completely segmented. Experiments were performed on
      real and synthetic data comprised of 55 models and 610 scenes and an overall
      recognition rate of 95 percent was achieved. Comparison with the spin images
      revealed that our algorithm is superior in terms of recognition rate and
      efficiency.

PMID- 16986542
TI  - Integral invariants for shape matching.
AB  - For shapes represented as closed planar contours, we introduce a class of
      functionals which are invariant with respect to the Euclidean group and which are
      obtained by performing integral operations. While such integral invariants enjoy
      some of the desirable properties of their differential counterparts, such as
      locality of computation (which allows matching under occlusions) and uniqueness
      of representation (asymptotically), they do not exhibit the noise sensitivity
      associated with differential quantities and, therefore, do not require
      presmoothing of the input shape. Our formulation allows the analysis of shapes at
      multiple scales. Based on integral invariants, we define a notion of distance
      between shapes. The proposed distance measure can be computed efficiently and
      allows warping the shape boundaries onto each other; its computation results in
      optimal point correspondence as an intermediate step. Numerical results on shape
      matching demonstrate that this framework can match shapes despite the deformation
      of subparts, missing parts and noise. As a quantitative analysis, we report
      matching scores for shape retrieval from a database.

PMID- 16986543
TI  - Rotation forest: A new classifier ensemble method.
AB  - We propose a method for generating classifier ensembles based on feature
      extraction. To create the training data for a base classifier, the feature set is
      randomly split into K subsets (K is a parameter of the algorithm) and Principal
      Component Analysis (PCA) is applied to each subset. All principal components are
      retained in order to preserve the variability information in the data. Thus, K
      axis rotations take place to form the new features for a base classifier. The
      idea of the rotation approach is to encourage simultaneously individual accuracy
      and diversity within the ensemble. Diversity is promoted through the feature
      extraction for each base classifier. Decision trees were chosen here because they
      are sensitive to rotation of the feature axes, hence the name "forest." Accuracy
      is sought by keeping all principal components and also using the whole data set
      to train each base classifier. Using WEKA, we examined the Rotation Forest
      ensemble on a random selection of 33 benchmark data sets from the UCI repository
      and compared it with Bagging, AdaBoost, and Random Forest. The results were
      favorable to Rotation Forest and prompted an investigation into diversity
      accuracy landscape of the ensemble models. Diversity-error diagrams revealed that
      Rotation Forest ensembles construct individual classifiers which are more
      accurate than these in AdaBoost and Random Forest, and more diverse than these in
      Bagging, sometimes more accurate as well.

PMID- 16986544
TI  - Affine parameter estimation from the trace transform.
AB  - In this paper, we assume that we are given the images of two segmented objects,
      one of which may be an affinely distorted version of the other, and wish to
      recover the values of the parameters of the affine transformation between the two
      images. The images may also differ by the overall level of illumination. The
      multiplicative constant of such difference may also be recovered. We present a
      generic theoretical framework to solve this problem. In terms of this framework,
      other proposed methods may be interpreted. We show how, in this framework, one
      can recover the affine parameters in a way that is robust to various effects,
      such as occlusion and illumination variation. The proposed method is generic
      enough to be applicable also to matching two images that do not depict the same
      scene or object.

PMID- 16986545
TI  - Graphical models and point pattern matching.
AB  - This paper describes a novel solution to the rigid point pattern matching problem
      in Euclidean spaces of any dimension. Although we assume rigid motion, jitter is
      allowed. We present a noniterative, polynomial time algorithm that is guaranteed
      to find an optimal solution for the noiseless case. First, we model point pattern
      matching as a weighted graph matching problem, where weights correspond to
      Euclidean distances between nodes. We then formulate graph matching as a problem
      of finding a maximum probability configuration in a graphical model. By using
      graph rigidity arguments, we prove that a sparse graphical model yields
      equivalent results to the fully connected model in the noiseless case. This
      allows us to obtain an algorithm that runs in polynomial time and is provably
      optimal for exact matching between noiseless point sets. For inexact matching, we
      can still apply the same algorithm to find approximately optimal solutions.
      Experimental results obtained by our approach show improvements in accuracy over
      current methods, particularly when matching patterns of different sizes.

PMID- 16986546
TI  - A neural network-based novelty detector for image sequence analysis.
AB  - This paper proposes a new model of "novelty detection" for image sequence
      analysis using neural networks. This model uses the concept of artificially
      generated negative data to form closed decision boundaries using a multilayer
      perceptron. The neural network output is novelty filtered by thresholding the
      output of multiple networks (one per known class) to which the sample is input
      and clustered for determining which clusters represent novel classes. After
      labeling these novel clusters, new networks are trained on this data. We perform
      experiments with video-based image sequence data containing a number of novel
      classes. The performance of the novelty filter is evaluated using two performance
      metrics and we compare our proposed model on the basis of these with five
      baseline novelty detectors. We also discuss the results of retraining each model
      after novelty detection. On the basis of Chi-square performance metric, we prove
      at 5 percent significance level that our optimized novelty detector performs at
      the same level as an ideal novelty detector that does not make any mistakes.

PMID- 16986547
TI  - The semantic pathfinder: using an authoring metaphor for generic multimedia
      indexing.
AB  - This paper presents the semantic pathfinder architecture for generic indexing of
      multimedia archives. The semantic pathfinder extracts semantic concepts from
      video by exploring different paths through three consecutive analysis steps,
      which we derive from the observation that produced video is the result of an
      authoring-driven process. We exploit this authoring metaphor for machine-driven
      understanding. The pathfinder starts with the content analysis step. In this
      analysis step, we follow a data-driven approach of indexing semantics. The style
      analysis step is the second analysis step. Here, we tackle the indexing problem
      by viewing a video from the perspective of production. Finally, in the context
      analysis step, we view semantics in context. The virtue of the semantic
      pathfinder is its ability to learn the best path of analysis steps on a per
      concept basis. To show the generality of this novel indexing approach, we develop
      detectors for a lexicon of 32 concepts and we evaluate the semantic pathfinder
      against the 2004 NIST TRECVID video retrieval benchmark, using a news archive of
      64 hours. Top ranking performance in the semantic concept detection task
      indicates the merit of the semantic pathfinder for generic indexing of multimedia
      archives.

PMID- 16986548
TI  - Fast active appearance model search using canonical correlation analysis.
AB  - A fast AAM search algorithm based on canonical correlation analysis (CCA-AAM) is
      introduced. It efficiently models the dependency between texture residuals and
      model parameters during search. Experiments show that CCA-AAMs, while requiring
      similar implementation effort, consistently outperform standard search with
      regard to convergence speed by a factor of four.

PMID- 16986549
TI  - Multiple nose region matching for 3D face recognition under varying facial
      expression.
AB  - An algorithm is proposed for 3D face recognition in the presence of varied facial
      expressions. It is based on combining the match scores from matching multiple
      overlapping regions around the nose. Experimental results are presented using the
      largest database employed to date in 3D face recognition studies, over 4,000
      scans of 449 subjects. Results show substantial improvement over matching the
      shape of a single larger frontal face region. This is the first approach to use
      multiple overlapping regions around the nose to handle the problem of expression
      variation.

PMID- 16986550
TI  - Iterative local-global energy minimization for automatic extraction of objects of
      interest.
AB  - We propose a novel global-local variational energy to automatically extract
      objects of interest from images. Previous formulations only incorporate local
      region potentials, which are sensitive to incorrectly classified pixels during
      iteration. We introduce a global likelihood potential to achieve better
      estimation of the foreground and background models and, thus, better extraction
      results. Extensive experiments demonstrate its efficacy.

PMID- 16986551
TI  - Overlapping events with application to image sequences.
AB  - Counting spatially and temporally overlapping events in image sequences and
      estimating their shape-size and duration features are important issues in some
      applications. We propose a stochastic model, a particular case of the
      nonisotropic 3D Boolean model, for performing this analysis: the temporal Boolean
      model. Some probabilistic properties are derived and a methodology for parameter
      estimation from time-lapse image sequences is proposed using an explicit
      treatment of the temporal dimension. We estimate the mean number of germs per
      unit area and time, the mean grain size and the duration distribution. A wide
      simulation study in order to assess the proposed estimators showed promising
      results. The model was applied on biological image sequences of in-vivo cells in
      order to estimate new parameters such as the mean number and duration
      distribution of endocytic events. Our results show that the proposed temporal
      Boolean model is effective for obtaining information about dynamic processes
      which exhibit short-lived, but spatially and temporally overlapping events.

PMID- 16986553
TI  - Janet Howard.

PMID- 16986554
TI  - The changing face of leadership.

PMID- 16986555
TI  - Good health for all.

PMID- 16986556
TI  - Change management and quality.

PMID- 16986557
TI  - Performance managing matrons.

PMID- 16986558
TI  - Role conflict: leaders and managers.

PMID- 16986559
TI  - Neonatal and perinatal mortality must be tackled globally.

PMID- 16986560
TI  - Antenatal therapy and prophylaxis for congenital cytomegalovirus infection.

PMID- 16986561
TI  - Opportunistic cervical screening at a sexual health clinic.
AB  - Women attending sexual health services may be higher risk for cervical cancer
      than the general population. In the United Kingdom, where a national cervical
      screening programme is underway, sexual health clinics no longer routinely offer
      their attendees cervical smears. Abnormal cervical smears add considerably to the
      workload of a sexual health service. In the absence of an organised national
      cervical screening programme in Ireland opportunistic screening is heavily relied
      upon. Opportunistic screening is performed in primary care, sexual health
      services and other women's health services. In the absence of this opportunistic
      cervical screening treatable pre-cancerous lesions may go unrecognised.

PMID- 16986562
TI  - Application of the Ottawa Knee Rules in assessing acute knee injuries.
AB  - The Ottawa Knee Rules (OKR) were established to identify which adults with acute
      knee injuries require knee x-rays as part of their assessment. This study
      evaluates the compliance of non-consultant hospital doctors (NCHDs), working in
      an Irish Emergency Dept., with these guidelines and assesses the impact of
      raising the profile of these rules on their implementation. Emergency Dept. (ED)
      notes of all adults who presented with an acute knee injury in a 3-month period
      were analysed retrospectively and compliance with the OKR was assessed. ED NCHDs
      were then educated on the details and value of these guidelines. In the
      subsequent three months, the improvement in compliance with the OKR was audited.
      In the initial audit, according to the Ottawa criteria, 65.5% of all x-rays of
      acute knee injuries were performed unnecessarily. In the second audit, performed
      after increasing awareness of the OKR, this figure had dropped to 39.1%. The
      NCHDs involved in this project cited 'patient expectation' for an x-ray as the
      primary reason why full compliance was not achieved. This study highlights a lack
      of awareness of and compliance with the OKR in the assessment of acute knee
      injuries in adults. It shows how the implementation of simple measures, which
      raised the profile of the OKR among ED staff, significantly improved compliance
      with the rules, thus cutting patient waiting times and cutting hospital costs.
      Futhermore, this study revealed that patients, when injured, expect to get x
      rayed and ofter doctors comply with these expectations even if no indication
      exists.

PMID- 16986563
TI  - Determinants of influenza vaccination uptake among hospital healthcare workers.
AB  - Influenza vaccination of health care workers is recommended for their own
      protection and that of their patients. There is serendipitous protection for
      their contacts outside of work. Influenza vaccination uptake has been
      historically poor. A questionnaire study of healthcare staff at a tertiary
      referral hospital was carried out to evaluate knowledge of and attitudes to
      influenza and its vaccine. There was a 36% response rate to the questionnaire,
      but with reasonably proportionate representation of the various occupational
      groups. The mean acceptance of vaccine in respondents was 30%; however the
      vaccination rate for the hospital in 2003 was 16.2% indicating that non-vaccinees
      were under represented in the study sample.. Vaccine uptake increased with age.
      Occupationally, doctors, clerical and catering/household staff had higher than
      mean reported uptake of vaccine. Nurse respondents reported vaccine uptake of
      22%. The role of these factors is examined in determining vaccine acceptance. A
      strong belief in the effectiveness of influenza vaccine was shown to be the
      strongest predictor of vaccine uptake with 66% of this group taking vaccine. A
      maximum score in an 8-question knowledge test was only associated with a 51%
      vaccine uptake. Implications for campaigns to improve uptake are discussed.

PMID- 16986564
TI  - Farmer's lung is now in decline.
AB  - Farmer's lung incidence in Ireland was constant until 1996, even though hay
      making methods were revolutionised in late 1980's. We undertook this study to
      find out the incidence of farmer's lung in Ireland from 1982-2002 and its
      correlation with rainfall and the effect of changing farm practices. The primary
      cases of farmer's lung were identified from Hospital in Patients Enquiry (HIPE)
      unit of the national Economic & Social Research Institute (ESRI) Dublin. Rainfall
      data were obtained from Met Eireann whereas population, hay production and silage
      production were obtained from the Central Statistics Office, Dublin. As the
      farming population is in decline, we used the annual working unit (AWU), which
      reflects the true population at risk. An AWU is the equivalent of 1800 hours per
      farm worker per year. The incidence rates were constant from 1982-1996, but from
      1997-2002 a marked decline was observed. There was strong positive correlation
      with hay production (r = 0.81) and strong negative correlation with silage
      production (r = -0.82). This study indicates that the incidence of farmer's lung
      is now in decline.

PMID- 16986565
TI  - The impact of antithrombotic therapy on neurosurgical emergency referral load.
AB  - The authors sought to determine the impact of antithrombotic therapy on emergency
      referrals at one neurosurgical centre. All emergency telephone referrals over a
      90 day period were carefully documented with particular attention paid to current
      antithrombotic medications and their indication. Details regarding age, gender,
      diagnosis, radiological findings and treatment were also recorded. 713 emergency
      referrals were documented in the data collection period. 174 (24.4%) patients
      presented with intracranial or spinal haemorrhage and 75 (43.1%) of these were on
      antithrombotic therapy, ranging in age from 46-94 years (mean 71.1 years) with 29
      (31.8%) on warfarin, 43 (47.2%) on aspirin and 15 (16.4%) on clopidogrel alone or
      in combination with another antithrombotic agent. 17 (22.6%) had no documented
      indication for antithrombotic therapy (all of these were on aspirin therapy) and
      9 (31%) of those on warfarin had an INR in excess of 3.5 on presentation. Almost
      one quarter of those on antithrombotic therapy who presented with a haemorrhagic
      complication had no obvious indication for such therapy. One third of those on
      warfarin were over anticoagulated.

PMID- 16986566
TI  - Dissatisfaction with Do Not Attempt Resuscitation Orders: A nationwide study of
      Irish consultant physician practices.
AB  - The legal/ethical status of Do Not Attempt Resuscitation (DNAR) orders in Ireland
      has not been clarified, nor have national policies been formulated. We questioned
      298 consultant physicians in the Republic of Ireland about DNAR orders. 173
      replies were received (58%). 85 expressed unsatisfactory understanding of issues
      relating to Irish DNAR orders (49%). 116 physicians felt that alert patients
      preferred not to discuss their own resuscitation (67%). 55 physicians felt that
      if a competent adult patient is the subject of a DNAR order without the patient's
      knowledge, the reasons for this decision are "almost never" documented in the
      patient's medical record (32%). 75 consultants "almost never" had advance
      discussion of resuscitation preferences with the patient (43%). 47 physicians had
      experienced advance directives for Irish patients (27%). 102 physicians felt that
      both they and the patient's next of kin had joint responsibility for deciding
      resuscitation status for an incapacitated patient with no advance directive
      (59%). 37 respondents described a formal resuscitation policy in their place of
      work (21%). We feel that physicians require greater national guidance regarding
      DNAR order-making, and we advocate more widespread use of resuscitation policies.

PMID- 16986567
TI  - Laparoscopic colorectal resection: initial experience in a specialist unit.
AB  - The adoption of the laparoscopic approach to colorectal resection has been slow
      amongst colorectal surgeons principally due to concerns regarding oncological
      safety. Recent randomized controlled trials have confirmed both the safe and some
      advantage of this procedure have been performing laparoscopic assisted colorectal
      resection since 2002 and have now performed over 100 cases on non consecutive and
      selected patients. We have reviewed our experience with the introduction of this
      technique. 61 patients were operated on for cancer and 39 for benign disease
      mainly Crohn's and diverticular disease. Operative time was a median of 128
      minutes over the course of study. Conversion rate was 5%. Pathological analysis
      of the resected specimens in the cancer cases revealed adequate lymph node
      harvest and margins. No patient had a positive margin and no port site metastasis
      have been seen. Duration of ileus and length of stay were a median of 0 and 6
      days. Post operative morbidity and mortality were comparable to open colorectal
      surgery with the exception of port site herniation which occurred in 4% of
      patients. This study suggests that a laparoscopic approach to colorectal
      resection can be successfully introduced in an Irish hospital setting. The
      challenge facing Irish surgery is to disseminate this technique in a controlled
      and safe manner for Irish patients.

PMID- 16986568
TI  - Legibility of doctor's signatures: novel approaches to improving an age-old
      problem.
AB  - In today's medico-legal environment, the importance of identification of the
      authors of notes in patient medical charts cannot be overemphasized. We evaluated
      three different techniques of signing patient notes, over a one month period, in
      order to determine which technique was the most effective in identifying the
      author of the note. Surgical NCHDs in our hospital were divided into three
      groups. Group 1 was asked to sign the notes as they normally would. Group 2 was
      asked to print their name in block capitals after their signature and Group 3 was
      given pens with a personal self inking stamp to be used in addition to signing
      the notes. The number of signatures in all the charts, compliance with the
      assigned technique and the legibility of signatures were calculated. RESULTS: in
      Group 1, all NCHDs signed their name when writing notes (100% compliance),
      however the NCHD's signature was identified only 37% of the time. In Groups 2
      (who signed in block capitals) and Group 3 (who used the pen with personalised
      stamp) the author was identifiable 100% of the time when the respective signing
      method was used. Using the pen with personalised self inking stamp was
      significantly more popular (77% compliance) compared to signing in block capitals
      (46% compliance). In conclusion the pen, with personalised self inking stamp,
      provides a fast and effective means to clarify signatures of NCHD's
      documentation, which is not only important in a day to day patient management,
      but is essential from a medico-legal stand point.

PMID- 16986569
TI  - Radiation enteropathy.
AB  - Radiation enteritis is a functional disorder of the intestine that occurs during
      or after a course of radiotherapy to the abdomen, pelvis or rectum. It presents
      in both an acute and chronic form and has sequelae that can be life threatening.
      As radiotherapy is now being used more than ever before in the treatment of solid
      organ malignancies in the abdomen and pelvis, the incidence of radiation
      enteropathy is likely to increase in the future. We present two patients with
      severe forms of this condition in order to clarify the salient issues regarding
      its diagnosis and, in particular, its distinction from mechanical bowel
      obstruction. We also review its pathophysiology, management and current
      preventative strategies.

PMID- 16986570
TI  - Coronary stent insertion into a 20-year-old Blalock-Taussig Shunt.
AB  - A 21 year-old female with complex congenital heart disease presented with
      declining exercise tolerance, presyncope and increasing cyanosis despite regular
      venesection. Her double inlet left ventricle with rudimentary right ventricle,
      restrictive ventricular septal defect and pulmonary stenosis had been managed
      with a Classic Left Blalock-Taussig (B-T) Shunt aged 2 months and a Modified
      Right B-T Shunt at 4 years. Aortography revealed a patent but significantly
      narrowed Left B-T shunt with impaired blood flow and an aneurysmal pulmonary
      artery. Angioplasty and stenting of the shunt was undertaken and a 4.0 x 12mm
      coronary stent deployed. The patient's arterial oxygen saturation improved from
      76% on pulse oximetry to 85% post procedure and she reported significantly
      improved exercise tolerance upon follow-up.

PMID- 16986571
TI  - Reversible dilated cardiomyopathy: an unusual presentation of thyrotoxicosis.

PMID- 16986574
TI  - Acknowledging the problem.

PMID- 16986575
TI  - Advocacy: necessity not luxury.

PMID- 16986576
TI  - User friendly at any age.

PMID- 16986577
TI  - Cultural concepts at the end of life.

PMID- 16986578
TI  - Technical seduction.

PMID- 16986579
TI  - Boosting the immune system.

PMID- 16986580
TI  - Genetics: is it part of your role?

PMID- 16986581
TI  - Depression and older people.
AB  - Nearly a third of older people admitted for acute hospital care experience
      depression. Rates of depression are even higher in care homes. The purpose of
      this article is to raise awareness among nurses of this debilitating condition
      and its potentially fatal consequences, and to suggest interventions that can
      bring about improvement. Although challenging for nurses, detecting and treating
      depression can bring enormous benefits for older people and, in some cases, can
      mean the difference between life and death.

PMID- 16986582
TI  - Understanding the lives of older gay people.
AB  - Ten research articles were examined with the aim of increasing our understanding
      of the lives of older gay people. It is clear from the literature that nurses
      must not rely on stereotypes of older gay people to inform their professional
      practice. It is also important for nurses to appreciate that older homosexuals
      have different health and social care needs from their heterosexual
      contemporaries.

PMID- 16986583
TI  - Enhancing individualised care.

PMID- 16986584
TI  - Practice nurses vital to tackling obesity.

PMID- 16986585
TI  - There are lessons to be learnt in the aftermath of a scandal.

PMID- 16986586
TI  - Supply and demand?

PMID- 16986587
TI  - Effective ward management.

PMID- 16986589
TI  - Management of suspected bacterial urinary tract infection.
AB  - New guidelines on the management of suspected bacterial urinary tract infection
      in adults have just been released by the Scottish Intercollegiate Guidelines
      Network (SIGN). The guidance states that the presence of bacteriuria should lead
      to antibiotic treatment only when there is definitive evidence that eradicating
      the bacterial infection will result in a tangible health gain at a reasonable
      level of risk (SIGN, 2006).

PMID- 16986590
TI  - Laryngeal mask airway.
AB  - The laryngeal mask airway (LMA) was first used in anaesthetic practice in the
      1980s. It is now increasingly promoted as a first-line airway device during
      resuscitation, if a practitioner skilled in tracheal intubation is not available
      (Resuscitation Council (UK), 2002).

PMID- 16986591
TI  - Understanding how viruses can cause malignant disease.
AB  - This article discusses the contribution made by viral infections to the global
      burden of cancer. The greatest impact of virally-induced cancers is felt in the
      developing world--in those countries that experience greatest difficulty in
      meeting the costs of vaccination programmes. Support by wealthier nations for
      vaccination programmes, organised through the World Health Organization, could
      have an enormous impact on the global burden of disease and specifically on
      cancer incidence.

PMID- 16986592
TI  - Ongoing quality monitoring and enhancement explained.
AB  - The University of Northampton (formerly University College Northampton) was one
      of five sites selected to pilot ongoing quality monitoring and enhancement
      (OQME). The process measures the quality of healthcare education programmes
      provided by academic institutions and clinical learning environments using an
      integrated and streamlined system. This article describes OQME from a clinical
      placement perspective.

PMID- 16986593
TI  - A critical approach to evidence provided through clinical trials.
AB  - Debates continue about what is the best and most worthwhile approach to
      healthcare research. This article aims to encourage a critical approach to the
      concept of evidence and in particular suggests some reasons to question the
      prominence of randomised controlled trials (RCTs).

PMID- 16986594
TI  - Understanding difficult-to-control asthma.

PMID- 16986595
TI  - A guide to regulation of blood gases: part one.

PMID- 16986596
TI  - Why horse behaviour is important to the equine clinician.

PMID- 16986597
TI  - The clinical significance of sialoderiveratives in the search for novel means of
      antipathogen therapy.

PMID- 16986598
TI  - Dynamic obstructions of the equine upper respiratory tract. Part 1: observations
      during high-speed treadmill endoscopy of 600 Thoroughbred racehorses.
AB  - REASONS FOR PERFORMING STUDY AND OBJECTIVE: To review the prevalence of single
      and complex forms of dynamic airway obstructions within a large group of
      Thoroughbred horses in training referred for investigation of poor performance.
      METHODS: Video-endoscopic recordings of the upper respiratory tract made during a
      standardised treadmill exercise test of 600 Thoroughbred racehorses were reviewed
      and analysed in real time and slow motion to identify dynamic collapse by the
      tissues bordering onto the pharyngeal and laryngeal airways. RESULTS: Dynamic
      collapse within the nasopharynx or larynx was confirmed in 471 of the 600 horses.
      Dorsal displacement of the soft palate (DDSP; 50%) and palatal instability (33%)
      were the disorders most frequently identified. It was concluded that deglutition
      is not a significant event in the triggering of DDSP. Complex forms of dynamic
      collapse were present in 30% of the horses with upper respiratory tract
      obstructions. A significant influence of age on the prevalence of DDSP and
      dynamic laryngeal collapse was identified. There was an increased risk of DDSP in
      younger horses, and of laryngeal collapse in older horses. No association with
      gender or format of racing was identified. CONCLUSIONS AND POTENTIAL RELEVANCE:
      Palatal instability and DDSP comprised the most frequently encountered forms of
      dynamic collapse within the upper respiratory tract of the Thoroughbred
      racehorses in this study and are probably expressions of the same nasopharyngeal
      malfunction. Complex obstructions, i.e. where more than one structure collapses
      into the airway, occur frequently and therefore treatments that address solitary
      disorders may often be unsuccessful. Younger horses were found to be at greater
      risk of sustaining DDSP while older horses seemed more at risk to vocal cord
      collapse but not to collapse of the arytenoid cartilage itself.

PMID- 16986600
TI  - Equine mandibular gland: in situ characterisation of sialoderivatives.
AB  - REASONS FOR PERFORMING STUDY: Sialic acids modulate the metabolite transport
      across membranes and may be involved in protection against pathogenic agents. The
      presence of sialoderivatives in the equine mandibular gland requires further
      study. OBJECTIVE: To biochemically visualise in situ the presence of
      sialoderivatives, by means of mild and strong periodate oxidation and alcoholic
      saponification, combined with lectin histochemistry and sialidase digestion in
      order to hypothesise roles for detached sialoderivatives. METHODS: Mandibular
      glands were removed from 8 mature horses of both sexes and subjected to
      histochemical procedures, including periodate oxidation, saponfication and lectin
      staining. Controls were based upon the omission of peroxidase-conjugated lectins
      and respective enzyme-free buffers. RESULTS: The reactivities of PNA and RCA I
      lectins were affected by sialidase treatment, whether preceded by saponification
      or not, showing that the dimer N-acetyl-sialic acid-beta-Gal was linked (1
      3)GalNAc and (1-4)GlcNAc. In acinar cells the sequence sialic acid-beta-Gal(1
      3)GalNAc showed sialic residues acetylated at C4 only and at C4 and C7 and/or C8
      and/or C9(alpha2-6Gal) in both sexes, while in female mandibular gland also C4
      and C9(alpha2-3Gal) acetylated residues were present. Sialic acid linked to beta
      Gal(1-4)GlcNAc was prevalently C4 and C7 and/or C8 and/or C9(alpha2-6Gal and
      alpha2-3Gal) acetylated, whereas only a minor quantity showed acetyl groups at C7
      and/or C8 and/or C9(alpha2-6Gal) in the acinar cells of both sexes. CONCLUSIONS:
      The great variety of sialic acid residues expressed by equine mandibular gland
      could assume an important role in the defensive mechanisms towards pathogen
      agents and, compared with those of cattle, probably represents an example of
      molecular species-specificity related to different alimentary habits.

PMID- 16986599
TI  - Dynamic obstructions of the equine upper respiratory tract. Part 2: comparison of
      endoscopic findings at rest and during high-speed treadmill exercise of 600
      Thoroughbred racehorses.
AB  - REASONS FOR PERFORMING STUDY: The reliability of diagnoses of obstructive
      conditions of the upper respiratory tract (URT) based on examinations performed
      at rest vs. at exercise is controversial. OBJECTIVE: To compare diagnosis of URT
      by endoscopy at rest with that achieved during high-speed treadmill exercise
      (HSTE). HYPOTHESIS: Endoscopy of URT at rest, when performed in isolation from
      other simpler techniques is unreliable in the prediction of dynamic respiratory
      obstructions. METHODS: Endoscopic findings of 600 Thoroughbred racehorses during
      quiet breathing were compared with findings during high-speed treadmill exercise.
      Other parameters were also assessed for their specificity in diagnosis. RESULTS:
      Endoscopy of the resting horse showed low sensitivity (0.15) in the diagnosis of
      dorsal displacement of the soft palate (DDSP) and palatal instability (PI). When
      endoscopy and reported noises were taken together there was still a 35%
      misdiagnosis rate. Although there was significant association between resting
      laryngeal function score (LFS) and dynamic vocal cord and/or arytenoid cartilage
      collapse at exercise, 19% of horses with a grade 4/5 LFS were able to attain and
      maintain full abduction during exercise and 7% of those with 'normal' grades 1 or
      2 LFS at rest showed dynamic laryngeal collapse when exerted. Sensitivity of the
      diagnostic model was greatly increased (80%) when a history of inspiratory noise
      and palpable intrinsic muscle atrophy were included. CONCLUSIONS AND POTENTIAL
      RELEVANCE: Endoscopy of the upper respiratory tract of static horses is
      unreliable in the diagnosis of dynamic obstructions of the URT and should not be
      used in isolation in surgical decision-making or in the assessment of horses at
      the time of sale.

PMID- 16986601
TI  - Comparison of the antioxidant status in tracheal and bronchoalveolar epithelial
      lining fluids in recurrent airway obstruction.
AB  - REASONS FOR PERFORMING STUDY: Following a period of airway inflammation the
      clearance of inflammatory cells along the mucociliary escalator may impose a
      considerable oxidant load on the trachea. OBJECTIVES: To determine the degree of
      oxidative stress in tracheal epithelial lining fluid (ELF) in comparison to that
      present in peripheral airways after an acute exposure to organic dust. METHODS:
      Tracheal wash fluid and bronchoalveolar lavage fluid (BALF) were collected for
      cytology and antioxidant analyses from 6 recurrent airway obstruction (RAO)
      affected horses and 6 healthy control horses before and after stabling on straw
      bedding for 24 h. RESULTS: In RAO-affected horses, organic dust exposure resulted
      in a significant decrease in ascorbic acid concentration in tracheal ELF
      (P<0.0001), which was greater than the decrease in bronchoalveolar ELF (P =
      0.0003). The percentage decrease in tracheal ELF ascorbic acid correlated with
      the percentage decrease in bronchoalveolar ELF ascorbic acid (r = 0.76; P =
      0.004) following exposure. CONCLUSIONS: Acute organic dust exposure results in
      significant antioxidant depletion in the trachea, which may reflect inflammation
      and oxidative processes in peripheral airways. POTENTIAL RELEVANCE: Further work
      is required to evaluate the role of ascorbic acid depletion in the pathogenesis
      of RAO.

PMID- 16986602
TI  - Standing surgical repair of propagating metacarpal and metatarsal condylar
      fractures in racehorses.
AB  - REASONS FOR PERFORMING STUDY: Repair of spiral and long diaphyseal metacarpal and
      metatarsal fractures under anaesthesia can be problematic and associated with a
      high incidence of complications, including fracture propagation necessitating
      euthanasia. OBJECTIVE: To report on a practical repair technique for which
      general anaesthesia is not required. METHODS: Thirteen racehorses with a
      spiral/propagating condylar fracture had the fracture repaired using local
      anaesthesia and sedation, without the need for general anaesthetic. RESULTS: Ten
      of the horses returned to training and 8 raced again. Two horses were retired
      directly to stud. One horse had propagation of the fracture 3 days post surgery,
      and was subjected to euthanasia. CONCLUSIONS AND POTENTIAL RELEVANCE: Results
      achieved were comparable to those gained using standard repair techniques under
      general anaesthesia. The described technique removes the need for general
      anaesthesia for repair of selected condylar fractures.

PMID- 16986603
TI  - Meclofenamic acid extends donor-recipient asynchrony in equine embryo transfer.
AB  - REASONS FOR PERFORMING STUDY: A level of synchrony between embryo and uterine
      environment is essential for the establishment of pregnancy when performing
      embryo transfer. The ability to extend the acceptable degree of asynchrony would
      allow more efficient use of recipient mares. OBJECTIVES: To establish if
      administration of the prostaglandin synthetase inhibitor, meclofenamic acid, to
      asynchronous recipient mares could widen the acceptable window of asynchrony for
      embryo transfer. HYPOTHESIS: The prostaglandin synthetase inhibitory action of
      meclofenamic acid may act to suppress luteolysis and thereby allow for a greater
      degree of asynchrony between donor and recipient mares. METHODS: A total of 72
      Grade 1 horse embryos were transferred nonsurgically into the uteri of recipient
      mares that had ovulated 2 (n = 20), 3 (n = 20), 4 (n = 16) or 5 (n = 16) days
      before the donor. Half of the mares in each group were treated orally with 1 g
      meclofenamic acid, beginning on Day 9 after ovulation and continuing for 7 days
      after embryo transfer. RESULTS: Comparison of recipient:donor asynchrony between
      treated and untreated mares was: +2 days, 9/10 pregnancies vs. 8/10 (P= 1.00); by
      +3 days, 8/10 vs. 2/10 (P= 0.025); by +4 days, 5/8 vs. 1/8 (P = 0.121); and by +5
      days 3/8 vs. 0/8 (P = 0.20). In 10/11 meclofenamic acid-treated and 23/25
      untreated recipient mares that failed to become pregnant, luteolysis occurred at
      the normal time (14-19 days) after ovulation. CONCLUSION: Treatment with
      meclofenamic acid supported the establishment of pregnancy in recipient mares
      that ovulated before the donors. However, meclofenamic acid appeared to provide
      this support in a manner other than by suppression of luteolysis. POTENTIAL
      RELEVANCE: Pregnancy rates can be increased in recipient mares that ovulate 3
      days before the donor by administration of meclofenamic acid.

PMID- 16986604
TI  - Validity of a behavioural measure of heat stress and a skin tent test for
      dehydration in working horses and donkeys.
AB  - REASONS FOR PERFORMING STUDY: Dehydration and heat stress are serious welfare
      issues for equids working in developing countries. There is a lack of any
      standardised method or validated interpretation of the skin tent test in horses
      and donkeys. Owners of dehydrated and heat-stressed animals often depend on
      veterinary examination for identification of these conditions, leading to delays
      in treatment and unnecessary reliance on external sources to effect welfare
      improvement. OBJECTIVES: To validate a standardised skin tent test for
      dehydration and a behavioural measure of heat stress in working equids; and to
      examine the effect of heat stress and dehydration on tripping and staggering
      behaviour. METHODS: The study was carried out on 130 working horses and donkeys
      in Pakistan. Associations between skin tent and blood parameters (packed cell
      volume [PCV], serum total protein [TP], serum osmolality), clinical parameters,
      resting and drinking behaviour were examined. Heat stress behaviour (increased
      respiratory rate and depth, head nodding, flared nostrils, apathy) was observed
      in conjunction with rectal temperature. Tripping and staggering were assessed
      using a simple obstacle course. RESULTS: In both species, heat stress behaviour
      was significantly associated with increased rectal temperature (P<0.001). A
      positive skin tent test was not significantly associated with PCV or TP, although
      in donkeys it was significantly associated with lower serum osmolality (P<0.001).
      More animals age >15 years had a positive skin tent than those in younger age
      groups (P = 0.037). Very thin horses were more likely to have a positive skin
      tent than those in thin or moderate condition (P = 0.028). There was no
      significant correlation between skin tent and tripping or staggering in either
      species. CONCLUSIONS AND POTENTIAL RELEVANCE: Heat stress behaviour is related to
      increased body temperature in working horses and donkeys. Owners may use this to
      make judgements regarding rest and cooling, precluding the need to seek
      veterinary attention. The skin tent test for dehydration used in this study did
      not show a significant relationship with PCV or TP. However, the use of blood
      parameters to validate the skin tent test may be confounded by anaemia,
      hypoproteinaemia or electrolyte depletion. Alternative methods are needed to
      confirm or refute the validity of the skin tent test in working equids.

PMID- 16986605
TI  - Training methods for horses: habituation to a frightening stimulus.
AB  - REASONS FOR PERFORMING STUDY: Responses of horses in frightening situations are
      important for both equine and human safety. Considerable scientific interest has
      been shown in development of reactivity tests, but little effort has been
      dedicated to the development of appropriate training methods for reducing
      fearfulness. OBJECTIVES: To investigate which of 3 different training methods
      (habituation, desensitisation and counter-conditioning) was most effective in
      teaching horses to react calmly in a potentially frightening situation.
      HYPOTHESES: 1) Horses are able to generalise about the test stimulus such that,
      once familiar with the test stimulus in one situation, it appears less
      frightening and elicits a reduced response even when the stimulus intensity is
      increased or the stimulus is presented differently; and 2) alternative methods
      such as desensitisation and counter-conditioning would be more efficient than a
      classic habituation approach. METHODS: Twenty-seven naive 2-year-old Danish
      Warmblood stallions were trained according to 3 different methods, based on
      classical learning theory: 1) horses (n = 9) were exposed to the full stimulus (a
      moving, white nylon bag, 1.2 x 0.75 m) in 5 daily training sessions until they
      met a predefined habituation criterion (habituation); 2) horses (n = 9) were
      introduced gradually to the stimulus and habituated to each step before the full
      stimulus was applied (desensitisation); 3) horses (n = 9) were trained to
      associate the stimulus with a positive reward before being exposed to the full
      stimulus (counter-conditioning). Each horse received 5 training sessions of 3 min
      per day. Heart rate and behavioural responses were recorded. RESULTS: Horses
      trained with the desensitisation method showed fewer flight responses in total
      and needed fewer training sessions to learn to react calmly to test stimuli.
      Variations in heart rate persisted even when behavioural responses had ceased. In
      addition, all horses on the desensitisation method eventually habituated to the
      test stimulus whereas some horses on the other methods did not. CONCLUSIONS AND
      POTENTIAL RELEVANCE: Desensitisation appeared to be the most effective training
      method for horses in frightening situations. Further research is needed in order
      to investigate the role of positive reinforcement, such as offering food, in the
      training of horses.

PMID- 16986606
TI  - Racing performance after arthroscopic removal of apical sesamoid fracture
      fragments in Thoroughbred horses age > or = 2 years: 84 cases (1989-2002).
AB  - REASONS FOR PERFORMING STUDY: Studies have shown that surgical removal of apical
      fracture fragments in Standardbred racehorses carries the best prognosis for
      return to racing performance, but there are no reports involving mature
      Thoroughbred (TB) racehorses. OBJECTIVES: To describe the incidence of apical
      proximal sesamoid fractures in TB racehorses and determine probability and
      quality of racing performance after arthroscopic removal of such fractures in TB
      racehorses age > or = 2 years. METHODS: Medical records and pre- and post
      operative race records of TB racehorses age > or = 2 years that underwent
      arthroscopic surgery for removal of apical proximal sesamoid fracture fragments
      were reviewed. RESULTS: Sixty-four percent of fractures occurred in the hindlimbs
      and 36% in the forelimbs. Horses with forelimb fractures had a reduced
      probability of return to racing (67%) compared to those with hindlimb fractures
      (83%), but the majority (77%) of treated horses recovered to return to race post
      operatively. Horses with medial forelimb fractures raced at only a 47% rate;
      those with suspensory desmitis at 63%. Unlike Standardbreds, there was no
      difference in probability of racing post operatively between horses that had, and
      had not, raced preoperatively. CONCLUSIONS: Data show that arthroscopic removal
      of apical proximal sesamoid fracture fragments is successful at restoring ability
      to race in skeletally mature TB horses without evidence of severe suspensory
      ligament damage. Prognosis for return to racing is excellent (83%) in horses with
      hindlimb fractures and good (67%) in those with forelimb fractures. Medial
      fractures of the forelimb have the worst prognosis. POTENTIAL RELEVANCE: The
      determination of prognosis for differing sites in TB racehorses should increase
      knowledge of apical proximal sesamoid bone fractures and improve communication
      from veterinarian to owner, and trainer, on the potential for arthroscopic
      restoration of the ability to race.

PMID- 16986607
TI  - Laparoscopic application of PGE2 to re-establish oviducal patency and fertility
      in infertile mares: a preliminary study.
AB  - REASONS FOR PERFORMING STUDY: Mares are occasionally encountered that
      consistently fail to conceive when inseminated, naturally or artificially, with
      fertile stallion semen in the absence of any identifiable pathology of either the
      structure or function of their reproductive tract. HYPOTHESIS: Temporary blockage
      of the oviducts by accumulations of naturally occurring oviducal masses may be
      preventing oviducal transport of the embryo to the uterus. METHODS: Mares, with
      known reproductive histories, that had exhibited inexplicable failure of
      conception were treated by laparoscopically guided administration of PGE2-laced
      triacetin gel directly onto the surface of their oviducts. RESULTS: Fifteen mares
      age 10-21 years that had exhibited inexplicable failure of conception during 1-4
      years were treated, of which 14 (93%) conceived within the same or subsequent
      breeding season. CONCLUSIONS: The high success rate of this treatment supports
      the tentative diagnosis of oviducal obstruction in these mares and indicates that
      blockage of the mare's oviducts may occur in the form of a moveable accumulation
      of debris rather than from permanent fibrous adhesions resulting from
      salpingitis. POTENTIAL RELEVANCE: This laparoscopic application of PGE2 to the
      oviducts constitutes a sound and practical method of restoring fertility in mares
      suffering oviducal obstruction and further studies involving the procedure are
      warranted.

PMID- 16986608
TI  - Magnetic resonance microscopy of the equine hoof wall: a study of resolution and
      potential.
AB  - REASONS FOR PERFORMING STUDY: Obtaining magnetic resonance images of the inner
      hoof wall tissue at the microscopic level would enable early accurate diagnosis
      of laminitis and therefore more effective therapy. OBJECTIVES: To optimise
      magnetic resonance imaging (MRI) parameters in order to obtain the highest
      possible resolution of the structures beneath the equine hoof wall. METHODS:
      Magnetic resonance microscopy (MRM) was performed in front feet from 6 cadaver
      horses using T2-weighted fast spin echo (FSE-T2), and T1-weighted gradient echo
      (GRE-T1) sequences. RESULTS: In T2 weighted FSE images most of the stratum medium
      showed no signal, however the coronary, terminal and sole papillae were visible.
      The stratum lamellatum was clearly visible and primary epidermal lamellae could
      be differentiated from dermal lamellae. CONCLUSION: Most structures beneath the
      hoof wall were differentiated. Conventional scanners for diagnostic MRI in horses
      are low or high field. However this study used ultra-high field scanners
      currently not available for clinical use. Signal-to-noise ratio (S/N) increases
      as a function of field strength. An increase of spatial resolution of the image
      results in a decreased S/N. S/N can also be improved with better coils and the
      resolution of high field MRI scanners will increase as technology develops and
      surface array coils become more readily available. POTENTIAL RELEVANCE: Although
      MR images with microscopic resolution were obtained ex vivo, this study
      demonstrates the potential for detection of lamellar pathology as it occurs.
      Early recognition of the development of laminitis to instigate effective therapy
      at an earlier stage and may improve the outcome for laminitic horses. Clinical MR
      is now readily available at 3 T, while 4 T, 7 T and 9 T systems are being used
      for human whole body applications.

PMID- 16986609
TI  - Equine embryo transfer: review of developing potential.

PMID- 16986610
TI  - Post anaesthetic colic in horses: a preventable complication?
AB  - REASONS FOR PERFORMING STUDY: There is little information on the prevalence of,
      and risk factors associated with, post anaesthetic colic (PAC) in horses
      undergoing nonabdominal operations. OBJECTIVES: To undertake the first
      prospective study of prevalence of PAC and identify risk factors in its
      development in nonabdominal procedures. METHODS: A multicentre prospective case
      control study was conducted, on every horse undergoing anaesthesia for a
      nonabdominal procedure between April 2004 and June 2005. Colic cases were defined
      as any horse with recognised signs of abdominal pain within 72 h of general
      anaesthesia that could not be attributed to any concurrent disease. Five control
      horses per case were selected randomly from the study population at all
      hospitals. Multivariable logistic regression analysis was used to examine the
      relationship between predictor variables and the risk of developing PAC. RESULTS:
      The estimated mean prevalence of PAC in the study population was 5.2% (95% CI,
      2.8, 8.0). However, the prevalence of colic varied between each centre. The most
      commonly diagnosed cause of colic was impaction. Multivariable analyses showed
      that the centre involved and the type of surgery performed were associated with
      an increased risk of PAC. Preoperative food deprivation and the use of opioid
      drugs were confounding factors. CONCLUSIONS: Prevalence of PAC varied
      significantly between the 4 hospitals studied; there may be hospital-related
      covariates that account for this. The type of surgery performed influenced the
      risk of PAC. POTENTIAL RELEVANCE: Identifying the risk factors for PAC is a
      prerequisite for its prevention. This study indicates horses at increased risk of
      PAC that might benefit from a more critical evaluation of post anaesthetic
      gastrointestinal function and/or the provision of preventative measures. Further
      investigation is required to explain the variation in prevalence of PAC between
      centres.

PMID- 16986611
TI  - Immunolocalisation of desmoglein-1 in equine muzzle skin.

PMID- 16986612
TI  - Staffing lawsuits.

PMID- 16986613
TI  - Salary lawsuit.

PMID- 16986614
TI  - New study links nurse shortage to nurse pay. Unions raise nurses' pay and
      increase nurse/patient staffing ratios.

PMID- 16986615
TI  - Genomes to systems 2006.

PMID- 16986616
TI  - Circular causality.
AB  - The problem of disentangling complex dynamic systems is addressed, especially
      with a view to identifying those variables that take part in the essential
      qualitative behaviour of systems. The author presents a series of reflections
      about the methods of formalisation together with the principles that govern the
      global operation of systems. In particular, a section on circuits, nuclei, and
      circular causality and a rather detailed description of the analytic use of the
      generalised asynchronous logical description, together with a brief description
      of its synthetic use (OreverseO logic). Some basic rules are recalled, such as
      the fact that a positive circuit is a necessary condition of multistationarity.
      Also, the interest of considering as a model, rather than a well-defined set of
      differential equations, a variety of systems that differ from each other only by
      the values of constant terms is emphasised. All these systems have a common
      Jacobian matrix and for all of them phase space has exactly the same structure.
      It means that all can be partitioned in the same way as regards the signs of the
      eigenvalues and thus as regards the precise nature of any steady states that
      might be present. Which steady states are actually present, depends on the values
      of terms of order zero in the ordinary differential equations (ODEs), and it is
      easy to find for which values of these terms a given point in phase space is
      steady. Models can be synthesised first at the level of the circuits involved in
      the Jacobian matrix (that determines which types and numbers of steady states are
      consistent with the model), then only at the level of terms of order zero in the
      ODE's (that determines which of the steady states actually exist), hence the
      title 'Circular casuality'.

PMID- 16986617
TI  - Methods of robustness analysis for Boolean models of gene control networks.
AB  - As a discrete approach to genetic regulatory networks, Boolean models provide an
      essential qualitative description of the structure of interactions among genes
      and proteins. Boolean models generally assume only two possible states (expressed
      or not expressed) for each gene or protein in the network, as well as a high
      level of synchronisation among the various regulatory processes. Two possible
      methods of adapting qualitative models to incorporate the continuous-time
      character of regulatory networks, are discussed and compared. The first method
      consists of introducing asynchronous updates in the Boolean model. In the second
      method, the approach introduced by Glass is adopted to obtain a set of piecewise
      linear differential equations that continuously describe the states of each gene
      or protein in the network. Both methods are applied to a Boolean model of the
      segment polarity gene network of Drosophila melanogaster. The dynamics of the
      model is analysed, and a theoretical characterisation of the model's gene pattern
      prediction is provided as a function of the timescales of the various processes.

PMID- 16986618
TI  - Parameter estimation in stochastic biochemical reactions.
AB  - Gene regulatory, signal transduction and metabolic networks are major areas of
      interest in the newly emerging field of systems biology. In living cells,
      stochastic dynamics play an important role; however, the kinetic parameters of
      biochemical reactions necessary for modelling these processes are often not
      accessible directly through experiments. The problem of estimating stochastic
      reaction constants from molecule count data measured, with error, at discrete
      time points is considered. For modelling the system, a hidden Markov process is
      used, where the hidden states are the true molecule counts, and the transitions
      between those states correspond to reaction events following collisions of
      molecules. Two different algorithms are proposed for estimating the unknown model
      parameters. The first is an approximate maximum likelihood method that gives good
      estimates of the reaction parameters in systems with few possible reactions in
      each sampling interval. The second algorithm, treating the data as exact
      measurements, approximates the number of reactions in each sampling interval by
      solving a simple linear equation. Maximising the likelihood based on these
      approximations can provide good results, even in complex reaction systems.

PMID- 16986619
TI  - Multiple equilibria in complex chemical reaction networks: extensions to
      entrapped species models.
AB  - In two earlier papers, means were provided to decide the capacity of complex
      chemical reaction networks, taken with mass-action kinetics, to admit multiple
      equilibria in the context of the isothermal homogeneous continuous flow stirred
      tank reactor (CFSTR). In such a reactor, all species are deemed to be in the
      outflow, a fact which has an important bearing on the nature of the governing
      equations. In contrast, one can imagine CFSTR-like models of the cell in which
      certain large molecules (e.g., enzymes) remain entrapped within the cell, whereas
      smaller ones (e.g., metabolites) are free to diffuse through the cell boundary.
      Although such models bear a strong physical resemblance to the classical CFSTR
      picture, there are substantive differences in the corresponding mathematics.
      Without a presumption of mass-action kinetics, this research is intended to
      indicate a general way in which results about uniqueness of equilibria in the
      classical CFSTR context extend to entrapped species models.

PMID- 16986620
TI  - Use and abuse of the quasi-steady-state approximation.
AB  - The transient kinetic behaviour of an open single enzyme, single substrate
      reaction is examined. The reaction follows the Van Slyke-Cullen mechanism, a
      spacial case of the Michaelis-Menten reaction. The analysis is performed both
      with and without applying the quasi-steady-state approximation. The analysis of
      the full system shows conditions for biochemical pathway coupling, which yield
      sustained oscillatory behaviour in the enzyme reaction. The reduced model does
      not demonstrate this behaviour. The results have important implications in the
      analysis of open biochemical reactions and the modelling of metabolic systems.

PMID- 16986621
TI  - Metabolic futile cycles and their functions: a systems analysis of energy and
      control.
AB  - It has long been hypothesised that futile cycles in cellular metabolism are
      involved in the regulation of biochemical pathways. Following the work of
      Newsholme and Crabtree, a quantitative theory was developed for this idea based
      on open-system thermodynamics and metabolic control analysis. It is shown that
      the stoichiometric sensitivity of an intermediary metabolite concentration with
      respect to changes in steady-state flux is governed by the effective equilibrium
      constant of the intermediate formation, and the equilibrium can be regulated by a
      futile cycle. The direction of the shift in the effective equilibrium constant
      depends on the direction of operation of the futile cycle. High stoichiometric
      sensitivity corresponds to ultrasensitivity of an intermediate concentration to
      net flow through a pathway; low stoichiometric sensitivity corresponds to super
      robustness of concentration with respect to changes in flux. Both cases
      potentially play important roles in metabolic regulation. Futile cycles actively
      shift the effective equilibrium by expending energy; the magnitude of changes in
      effective equilibria and sensitivities is a function of the amount of energy used
      by a futile cycle. This proposed mechanism for control by futile cycles works
      remarkably similar to kinetic proofreading in biosynthesis. The sensitivity of
      the system is also intimately related to the rate of concentration fluctuations
      of intermediate metabolites. The possibility of different roles for the two major
      mechanisms within cellular biochemical regulation, namely reversible chemical
      modifications via futile cycles and shifting equilibrium by macromolecular
      binding, are discussed.

PMID- 16986622
TI  - Comparative study of parameter sensitivity analyses of the TCR-activated Erk-MAPK
      signalling pathway.
AB  - Parameter estimation is a major challenge for mathematical modelling of
      biological systems. Given the uncertainties associated with model parameters, it
      is important to understand how sensitive the model output is to variations in
      parameter values. A local sensitivity analysis determines the model sensitivity
      to parameter variations over a localised region around the nominal parameter
      values, whereas a global sensitivity analysis (GSA) investigates the sensitivity
      over the entire parameter space. Using a T-cell receptor-activated Erk-MAPK
      signalling pathway model as an example, the authors present a comparative study
      of a variety of different sensitivity analysis techniques. These techniques
      include: local sensitivity analysis, existing GSA methods of partial rank
      correlation coefficient, Sobol's, extended Fourier amplitude sensitivity test, as
      well as a weighted average of local sensitivities and a new GSA method to extract
      global parameter sensitivities from a parameter identification routine. Results
      of this study revealed critical reactions in the signalling pathway and their
      impact on the signalling dynamics and provided insights into embedded regulatory
      mechanisms such as feedback loops in the pathway. From this study, a
      recommendation emerges for a general sensitivity analysis strategy to efficiently
      and reliably infer quantitative, dynamic as well as topological properties from
      systems biology models.

PMID- 16986623
TI  - Can biochemical properties serve as selective pressure for gene selection during
      inter-species and endosymbiotic lateral gene transfer?
AB  - During the evolution of endosymbiosis, only one orthologous gene, either from the
      invader or the invaded genome, is preserved. Genetic and environmental factors
      are usually invoked to explain this gene preference. How biochemical parameters
      can play a role in the selection of genes that code for enzymes that constitute a
      metabolic pathway is explored. Simple Michaelis-Menten-like enzymes are
      considered whose kinetic parameters are randomly generated to construct two
      parallel homologous pathways to account for the contributions of the invaded and
      the invader. Steady-state fluxes as targets of natural selection are focused.
      Enzymes are eliminated one by one so that the total flux through the pathway is
      least disturbed. Analysis of the results, done by different criteria, indicate
      that the maximal velocities, both forward and backward, are more influential in
      selection than the respective Michaelis constants. This inclination disappears as
      metabolite concentrations are increased. It is shown that kinetic selection
      criteria can result in a mosaicism of enzymes in the same pathway in terms of
      their genetic origin. Analysis of the results using the control coefficient
      paradigm disclosed an expected robust correlation between flux control
      coefficients of enzymes and their selective elimination. Similar analyses,
      performed for the case of single gene transfer or for gene replication with
      subsequent mutation, yielded essentially similar results. The results conform
      with the phenomenon of genetic mosaicism found in phylogenetic analyses of single
      or double endosymbioses and lateral gene transfer.

PMID- 16986624
TI  - In silico evolution of functional modules in biochemical networks.
AB  - Understanding the large reaction networks found in biological systems is a
      daunting task. One approach is to divide a network into more manageable smaller
      modules, thus simplifying the problem. This is a common strategy used in
      engineering. However, the process of identifying biological modules is still in
      its infancy and very little is understood about the range and capabilities of
      motif structures found in biological modules. In order to delineate these
      modules, a library of functional motifs has been generated via in silico
      evolution techniques. On the basis of their functional forms, networks were
      evolved from four broad areas: oscillators, bistable switches, homeostatic
      systems and frequency filters. Some of these motifs were constructed from simple
      mass action kinetics, others were based on Michaelis-Menten kinetics as found in
      protein/protein networks and the remainder were based on Hill equations as found
      in gene/protein interaction networks. The purpose of the study is to explore the
      capabilities of different network architectures and the rich variety of
      functional forms that can be generated. Ultimately, the library may be used to
      delineate functional motifs in real biological networks.

PMID- 16986626
TI  - Reconstructing gene regulatory networks: from random to scale-free connectivity.
AB  - The manipulation of organisms using combinations of gene knockout, RNAi and drug
      interaction experiments can be used to reveal regulatory interactions between
      genes. Several algorithms have been proposed that try to reconstruct the
      underlying regulatory networks from gene expression data sets arising from such
      experiments. Often these approaches assume that each gene has approximately the
      same number of interactions within the network, and the methods rely on prior
      knowledge, or the investigator's best guess, of the average network connectivity.
      Recent evidence points to scale-free properties in biological networks, however,
      where network connectivity follows a power-law distribution. For scale-free
      networks, the average number of regulatory interactions per gene does not
      satisfactorily characterise the network. With this in mind, a new reverse
      engineering approach is introduced that does not require prior knowledge of
      network connectivity and its performance is compared with other published
      algorithms using simulated gene expression data with biologically relevant
      network structures. Because this new approach does not make any assumptions about
      the distribution of network connections, it is suitable for application to scale
      free networks.

PMID- 16986625
TI  - Quantifying gene network connectivity in silico: scalability and accuracy of a
      modular approach.
AB  - Large, complex data sets that are generated from microarray experiments, create a
      need for systematic analysis techniques to unravel the underlying connectivity of
      gene regulatory networks. A modular approach, previously proposed by Kholodenko
      and co-workers, helps to scale down the network complexity into more
      computationally manageable entities called modules. A functional module includes
      a gene's mRNA, promoter and resulting products, thus encompassing a large set of
      interacting states. The essential elements of this approach are described in
      detail for a three-gene model network and later extended to a ten-gene model
      network, demonstrating scalability. The network architecture is identified by
      analysing in silico steady-state changes in the activities of only the module
      outputs, communicating intermediates, that result from specific perturbations
      applied to the network modules one at a time. These steady-state changes form the
      system response matrix, which is used to compute the network connectivity or
      network interaction map. By employing a known biochemical network, the accuracy
      of the modular approach and its sensitivity to key assumptions are evaluated.

PMID- 16986627
TI  - Unravelling gene networks from noisy under-determined experimental perturbation
      data.
AB  - Systems biology aims to study the properties of biological systems in terms of
      the properties of their molecular constituents. This occurs frequently by a
      process of mathematical modelling. The first step in this modelling process is to
      unravel the interaction structure of biological systems from experimental data.
      Previously, an algorithm for gene network inference from gene expression
      perturbation data was proposed. Here, the algorithm is extended by using
      regression with subset selection. The performance of the algorithm is extensively
      evaluated on a set of data produced with gene network models at different levels
      of simulated experimental noise. Regression with subset selection outperforms the
      previously stated matrix inverse approach in the presence of experimental noise.
      Furthermore, this regression approach enables us to deal with under
      determination, that is, when not all genes are perturbed. The results on
      incomplete data sets show that the new method performs well at higher number of
      perturbations, even when noise levels are high. At lower number of perturbations,
      although still being able to recover the majority of the connections, less
      confidence can be placed in the recovered edges.

PMID- 16986628
TI  - Parameter estimation in models combining signal transduction and metabolic
      pathways: the dependent input approach.
AB  - Biological complexity and limited quantitative measurements pose severe
      challenges to standard engineering methodologies for modelling and simulation of
      genes and gene products integrated in a functional network. In particular,
      parameter quantification is a bottleneck, and therefore parameter estimation,
      identifiability, and optimal experiment design are important research topics in
      systems biology. An approach is presented in which unmodelled dynamics are
      replaced by fictitious 'dependent inputs'. The dependent input approach is
      particularly useful in validation experiments, because it allows one to fit model
      parameters to experimental data generated by a reference cell type ('wild-type')
      and then test this model on data generated by a variation ('mutant'), so long as
      the mutations only affect the unmodelled dynamics that produce the dependent
      inputs. Another novel feature of the approach is in the inclusion of a priori
      information in a multi-objective identification criterion, making it possible to
      obtain estimates of parameter values and their variances from a relatively
      limited experimental data set. The pathways that control the nitrogen uptake
      fluxes in baker's yeast (Saccharomyces cerevisiae) have been studied. Well
      defined perturbation experiments were performed on cells growing in steady-state.
      Time-series data of extracellular and intracellular metabolites were obtained, as
      well as mRNA levels. A nonlinear model was proposed and was shown to be
      structurally identifiable given data of its inputs and outputs. The identified
      model is a reliable representation of the metabolic system, as it could correctly
      describe the responses of mutant cells and different perturbations.

PMID- 16986629
TI  - Unravelling the regulatory structure of biochemical networks using stimulus
      response experiments and large-scale model selection.
AB  - To unravel the complex in vivo regulatory interdependences of biochemical
      networks, experiments with the living organism are absolutely necessary. Stimulus
      response experiments (SREs) have become increasingly popular in recent years. The
      response of metabolite concentrations from all major parts of the central
      metabolism is monitored over time by modem analytical methods, producing several
      thousand data points. SREs are applied to determine enzyme kinetic parameters and
      to find unknown enzyme regulatory mechanisms. Owing to the complex regulatory
      structure of metabolic networks and the amount of measured data, the evaluation
      of an SRE has to be extensively supported by modelling. If the enzyme regulatory
      mechanisms are part of the investigation, a large number of models with different
      enzyme kinetics have to be tested for their ability to reproduce the observed
      behaviour. In this contribution, a systematic model-building process for data
      driven exploratory modelling is introduced with the aim of discovering essential
      features of the biological system. The process is based on data pre-processing,
      correlation-based hypothesis generation, automatic model family generation, large
      scale model selection and statistical analysis of the best-fitting models
      followed by an extraction of common features. It is illustrated by the example of
      the aromatic amino acid synthesis pathway in Escherichia coli.

PMID- 16986630
TI  - Regulation of glycolysis in Lactococcus lactis: an unfinished systems biological
      case study.
AB  - The unexpectedly long, and still unfinished, path towards a reliable mathematical
      model of glycolysis and its regulation in Lactococcus lactis is described. The
      model of this comparatively simple pathway was to be deduced from in vivo nuclear
      magnetic resonance time-series measurements of the key glycolytic metabolites. As
      to be expected from any nonlinear inverse problem, computational challenges were
      encountered in the numerical determination of parameter values of the model. Some
      of these were successfully solved, whereas others are still awaiting improved
      techniques of analysis. In addition, rethinking of the model formulation became
      necessary, because some generally accepted assumptions during model design are
      not necessarily valid for in vivo models. Examples include precursor-product
      relationships and the homogeneity of cells and their responses. Finally, it
      turned out to be useful to model only some of the metabolites, while using time
      courses of ubiquitous compounds such as adenosine triphosphate, inorganic
      phosphate, nicotinamide adenine dinucleotide (oxidised) and nicotinamide adenine
      dinucleotide (reduced) as unmodelled input functions. With respect to our
      specific application, the modelling process has come a long way, but it is not
      yet completed. Nonetheless, the model analysis has led to interesting insights
      into the design of the pathway and into the principles that govern its operation.
      Specifically, the widely observed feedforward activation of pyruvate kinase by
      fructose 1,6-bisphosphate is shown to provide a crucial mechanism for positioning
      the starving organism in a holding pattern that allows immediate uptake of
      glucose, as soon as it becomes available.

PMID- 16986631
TI  - From systems biology to dynamical neuropharmacology: proposal for a new
      methodology.
AB  - The concepts and methods of systems biology are extended to neuropharmacology in
      order to test and design drugs for the treatment of neurological and psychiatric
      disorders. Computational modelling by integrating compartmental neural modelling
      techniques and detailed kinetic descriptions of pharmacological modulation of
      transmitter-receptor interaction is offered as a method to test the
      electrophysiological and behavioural effects of putative drugs. Even more, an
      inverse method is suggested as a method for controlling a neural system to
      realise a prescribed temporal pattern. In particular, as an application of the
      proposed new methodology, a computational platform is offered to analyse the
      generation and pharmacological modulation of theta rhythm related to anxiety.

PMID- 16986632
TI  - Why physician groups are self-insuring.
AB  - Given the medical malpractice crisis in a number of states, many physicians are
      looking at alternatives to conventional insurance coverage. These options
      typically involve some form of risk sharing where the medical group assumes
      additional risks based on experience. This article identifies several options
      retrospective payment plans, risk retention groups, captives, and rent-a-captives
      -and their associated risks and opportunities.

PMID- 16986633
TI  - When disaster strikes: getting ready for the next big one: part I.
AB  - This two-part article deals with the role of the physician when disaster strikes.
      The first part concentrates on disaster planning and emergency preparedness as it
      pertains to the staff and the practice. It suggests points to consider in
      preparing a disaster plan for the practice or institution so that everyone knows
      what to do in the event of a crisis. This disaster plan is also a blueprint for
      recovery once the disaster has passed that will assure the financial health of
      the practice.

PMID- 16986634
TI  - Change your metrics: if you get what you measure, then measure what you want-
      retention.
AB  - What we want is retention, not turnover, of our workforce. We should measure what
      we want-net retention-which is a fundamentally different metric from turnover
      (not its inverse). Net retention is a highly useful managerial tool, especially
      for fiscal and strategic planning. Retention enables learning and therefore can
      facilitate improved medical and organizational outcomes. To retain our workforce
      and achieve superior results, we must clarify priorities; change our metrics,
      particularly to long-term outcomes; use evidence-based medicine and evidence
      based management; apply the "internal customer" concept; and utilize systems
      thinking.

PMID- 16986635
TI  - Office managers' perception of stress, control, and satisfaction: a comparison
      between primary care and specialty practices.
AB  - Perception of stress, control, and satisfaction was measured by office managers
      in medical practices. Office managers spend enormous amounts of time each day
      handling difficult interpersonal issues among staff physicians, and patients. As
      a group, physician disruptions were the most prevalent per day. Other staff
      members were considered the most stressful by rank order. Significant differences
      were discovered between primary care practices versus specialty practices in the
      areas of interactions with physicians.

PMID- 16986636
TI  - 25 tips for getting along with your co-workers.
AB  - Each member of the medical practice staff has the responsibility to develop
      positive relationships with his or her colleagues. Getting along is part of the
      job. Many employees do not realize this or they lack the tools to build strong co
      worker relationships. This article offers 25 specific strategies that will help
      the staff of a medical practice build positive co-worker relationships and avoid
      disputes. It describes ways each member of the team can improve communication
      skills and foster an atmosphere of respect. This article also suggests specific
      language employees can use with one another and several communication don'ts that
      can foil positive co-worker relationships. The 25 tips offered in this article
      can be the subject ofa staff meeting, used for new employee training, and printed
      in the medical practice's employee handbook.

PMID- 16986637
TI  - Leadership traits.

PMID- 16986638
TI  - Putting the "receive" in accounts receivable.
AB  - There isn't a practice in the United States that doesn't have a concern about
      accounts receivable. The financial success of any practice depends on the care
      and feeding of the accounts receivable. This is not an area of practice
      management that can be taken lightly or delegated to someone who is not attentive
      to detail and doggedly persistent. In this article, we will discuss how to
      identify problematic accounts receivable and what can be done to bring the
      accounts receivable under control. We will provide you with a plan of action that
      can be adopted by any practice regardless of size, number of physicians, or
      whether the practice uses in-house billing or outsources its billing
      arrangements.

PMID- 16986640
TI  - Cutting costs through prevention.
AB  - This is an examination of a proven model, developed by MDVIP, for delivering cost
      effective preventive medicine that is not possible in traditional primary care
      practices. Successful preventive care demands an in-depth assessment of health
      risk factors, appropriate screenings, and planning for long-term wellness goals
      based upon individual medical needs. In today's healthcare climate, the only way
      to offer comprehensive, quality service is by dramatically reducing practice size
      to no more than 600 patients, affording physicians the time needed to provide
      proactive medical care. The data show that with this model, patients have reduced
      hospital visits, shorter lengths of stay, and reduced costs. This model is
      commonly referred to as "concierge" medicine, of which MDVIP-affiliated
      physicians constitute 25 percent of the estimated 300 concierge practices
      nationally.

PMID- 16986639
TI  - Health savings accounts: should you consider these plans for your own staff?
AB  - Two of the latest buzzwords to take center stage in healthcare are health savings
      accounts (HSAs) and consumer-driven healthcare, but who knows what they mean?
      This article defines these two concepts and relates how they will work together
      to save money for consumers and drive down the cost of healthcare. Should
      physicians be concerned about the impact these initiatives will have on their
      practices? Physicians should always be concerned about what is going in the
      marketplace and do everything they can to prepare for the way new plans will
      affect patient behavior. As an employer, HSAs are worth considering for coverage
      for your practice staff Employers of all sizes are looking into ways these plans
      will save money yet provide the adequate coverage that employees hold dear. This
      article considers the characteristics of HSAs and explores the administrative and
      operational challenges HSAs will present.

PMID- 16986641
TI  - Academia and the medical group practice interface: the 2003 Institute of Medicine
      quality report and medication management.
AB  - University Physicians, Inc., has been impacted by the rising cost of professional
      liability insurance in recent years. Our internal risk management program needed
      to be enhanced to heighten provider sensitivity to the challenges certain
      practice processes (e.g., paper medical records) posed, and to tie this
      information to new patient and risk management strategies. The Institute of
      Medicine's 2003 report Priority Areas for National Action: Transforming Health
      Care Quality and the Agency for Healthcare Research and Quality's 2004 report
      Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies
      were used to establish priorities and develop indicators for measurement. A case
      study is presented on how these reports, combined with the Joint Commission on
      Accreditation of Healthcare Organization's 2006 National Patient Safety Goals for
      ambulatory care, were used to assess the group's risk profile and to implement
      practice changes to minimize risk.

PMID- 16986642
TI  - Consumers challenge accessibility under the ADA.

PMID- 16986643
TI  - Surgical malpractice: myths and realities.

PMID- 16986644
TI  - Practicing medicine in a new environment: what can we learn from the business
      managers?
AB  - Physicians, once only responsible for patient care, now are responsible for their
      organization's management. Although this paradigm shift occasioned much
      opposition, most aspects of this change are improving as the rules are
      reevaluated and reconsidered. Physician managers have difficult tasks for which
      medical school provides no preparation. Employees must be individually evaluated,
      so their unique talents can be properly exploited and appropriately compensated.
      Each person's weaknesses must be improved upon with delicacy, while his or her
      strengths are given greater and greater focus. This is especially true with
      regards to billing and coding because the financial health of all healthcare
      businesses requires organizational competence in this arena. It is vital to have
      an understanding of each staff member's skills, talents, and knowledge, and a
      proper deployment of each person into the appropriate job. The goal of any
      manager is a group of satisfied employees who enjoy their work and make
      appropriately recognized contributions.

PMID- 16986645
TI  - Online CME options: an update.
AB  - Online options for continuing medical education (CME) are multiplying, thanks to
      technologies such as really simple syndication (RSS) feeds, podcasts, and blogs.
      As with traditional CME modalities, there are issues of accreditation, quality,
      cost, and relevance. Physician-directed syndication technologies are especially
      significant in the area of relevance, because they provide subscriber-side
      filtering of the growing amount of information available online. As the medical
      education community embraces the technologies enabling targeted dissemination of
      information, physicians can expect more and better focused medical education
      experiences.

PMID- 16986646
TI  - What should your DRO be?: setting your DRO benchmark.

PMID- 16986647
TI  - Evaluation and management and modifiers: you too can find comfort in using them.

PMID- 16986648
TI  - Effects of social support and coping of family caregivers of older adults with
      dementia in Taiwan.
AB  - The purpose of this study was to explore the relationship of demographic
      characteristics, contextual factors, social support, and coping on health
      outcomes of family caregivers of older adults with dementia in Taiwan. This study
      also examined caregiving stress and whether support moderated the effects of
      caregiver stress on health. Lazarus and Folkman's (1984) Stress model guided this
      study. The descriptive cross-sectional study included subjects who were primary
      family caregivers of older adults with dementia from two settings in southern
      Taiwan. A convenience sample of 148 participants was interviewed. Data analysis
      consisted of Pearson's correlations, and simple and multiple regression analysis.
      Findings indicated that younger caregivers, those with paid assistants, and those
      with longer duration of caregiving had better health. Females with lower income
      and without assistants had more depressive symptoms. In addition, moderating
      effects of social support were supported. The results from this study provided a
      basis for developing interventions to minimize negative impacts on caregivers.

PMID- 16986649
TI  - Multiple role occupancy and social participation among midlife wives and husbands
      in the United Kingdom.
AB  - We investigated the relationship between intensive multiple role occupancy and
      one key dimension of well-being, social participation (i.e., frequency of
      participation in social and leisure activities and meeting friends or relatives).
      Moreover, we examined gender differences in the association between individual,
      spousal and couple intensive multiple role commitments and individual social
      participation. Our research is based on a sample of mid-life wives (45-59) and
      their husbands from the 2000 British Household Panel Study (BHPS). Our findings
      show that, among wives whose husbands were providing care to a dependent for 20
      or more hours a week, there was a negative association with social and leisure
      activity participation, whereas husbands' level of participation in social and
      leisure activities was higher if their wives were in full-time paid work. We also
      found lower odds of meeting friends or relatives among wives and husbands in full
      time employment, and higher odds of meeting friends and relatives among wives
      providing care for 20 or more hours a week. Our results will aid policy thinking
      in addressing how people can be best supported to balance work and family
      commitments in order to optimize different dimensions of well-being in later life
      and help alleviate the pressures associated with multiple-role occupancy in mid
      life.

PMID- 16986650
TI  - Lack of emotional support from parents early in life and alcohol abuse later in
      life.
AB  - The purpose of this study is to examine the association between lacking emotional
      support from parents early in life and adult alcohol abuse. A series of logistic
      regression models were run with data collected from a nationally representative
      sample of over 2500 adults ages 25-74. The findings reveal a linear relationship
      between level of deficiency in early maternal support and odds of alcohol abuse
      during adulthood, with even moderate deficiencies being associated with elevated
      risk. Further examination suggests that this association persists throughout
      adulthood. This association does not appear to be explained by the early
      initiation of alcohol use, but poor psychological well-being during adulthood
      does account for a large portion of this association. These findings expand our
      understanding of the risks associated with poor parental support during
      childhood, and underscore the importance of adopting a life course perspective in
      studying the social determinants of alcohol problems among adults.

PMID- 16986651
TI  - Spilling over strain between elders and their caregivers in Hong Kong.
AB  - According to the dialectical model, the well-being of the older care recipient,
      the informal caregiver, and the professional care provider mutually affect each
      other. Particularly, the caregiver's strain can affect the care recipient's well
      being both positively and negatively. Moreover, the task-specific model suggests
      that as social workers are responsible for maintaining elders' well-being, the
      workers' strain would be particularly influential on the elders' well-being. To
      clarify these dialectic relationships, the present study surveyed the three
      parties involved in home help or home care services in Hong Kong over two
      successive waves using a panel design. This study reveals the significant
      negative effect the professional care provider's earlier strain has on the
      elder's later well-being. Moreover, the social worker's earlier strain was
      particularly detrimental to the elder's later well-being. In contrast, the effect
      of the informal caregiver's earlier strain was not significant. Additionally, the
      elder's well-being had no significant impact on the strain of either the
      professional care provider or the informal caregiver. Findings of this study
      support the qualification of the dialectical model by the task-specific model to
      yield a model of channeled spillover. Accordingly, dialectical influence requires
      a channel to materialize the spillover effect.

PMID- 16986652
TI  - [Oxygen inhalation therapy].

PMID- 16986653
TI  - [Respiratory failure].

PMID- 16986654
TI  - [Treatments for acute respiratory failure].

PMID- 16986655
TI  - [Treatments for chronic respiratory failure].

PMID- 16986656
TI  - [Effects of oxygen inhalation on exercise-induced hypoxemia].

PMID- 16986657
TI  - [Basic knowledge for oxygen inhalation therapy].

PMID- 16986658
TI  - [Oxygen inhalation therapy--low oxygen-flow system with the nasal cannula].

PMID- 16986659
TI  - [Oxygen inhalation therapy--high oxygen-flow system with Ventulimask].

PMID- 16986660
TI  - [High flow oxygen inhalation therapy with the reservoir-attached oxygen mask].

PMID- 16986661
TI  - [High-flow Oxygen inhalation therapy with the oxygen tent].

PMID- 16986662
TI  - [Standardization of home oxygen inhalation therapy applicable for coverage by
      social health insurance in Japan].

PMID- 16986663
TI  - [Oxygen supply system for home oxygen inhalation therapy].

PMID- 16986664
TI  - [Social welfare for patients receiving home oxygen inhalation therapy].

PMID- 16986665
TI  - [Complication of oxygen inhalation therapy--carbon dioxide narcosis].

PMID- 16986666
TI  - [Oxygen poisoning].

PMID- 16986667
TI  - [Monitoring during oxygen inhalation therapy--pulse oximeter].

PMID- 16986668
TI  - [Safety management in oxygen inhalation therapy].

PMID- 16986669
TI  - [Dying with dignity].

PMID- 16986670
TI  - [Home care in intractable neurological diseases].
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- 16986671
TI  - [Network to support patients with ALS in the Hyogo prefecture].

PMID- 16986672
TI  - [What is QOL in the patient with incurable and intractable disease?--QOL
      evaluation and palliative care].

PMID- 16986673
TI  - [Familial Parkinsonism].

PMID- 16986674
TI  - [Cognitive function in patients with severe carotid stenosis--evaluation of
      RBANS, WAIS-R and NART before treatment of carotid revascularization--].
AB  - PURPOSE: To evaluate the cognitive function in preoperative patients with severe
      carotid stenosis. PATIENTS AND METHOD: Twenty-five patients with severe carotid
      stenosis were examined on their cognitive function by RBANS (Japanese version),
      WAIS-R (Japanese version), and NART (Japanese version) before treatment of
      carotid revascularization (endarterectomy or stenting). They had full activities
      of daily living without any hemiparesis, aphasia, agnosia, and apraxia at the
      time of the examinations. RESULTS: Mean intelligent quotient (IQ) measured by
      WAIS-R and NART was 104.0 +/- 10.7 and 101.3 +/- 13.4, (ns) respectively. Mean
      total scale of RBANS was 90.0 +/- 13.4, which was significantly lower than both
      the results of WAIS-R and NART. A mean value of each RBANS index was 91.3 +/-
      11.7 in immediate memory, 102.0 +/- 18.2 in visuospatial/constructional, 93.2 +/-
      8.7 in language, 84.6 +/- 14.7 in attention, and 92.1 +/- 14.4 in delayed memory.
      RBANS index significantly declined in immediate memory, language, attention and
      delayed memory than visuospatial/constructional. CONCLUSIONS: Qualitative
      evaluation was available in RBANS, WAIS-R, and NART, which enabled the
      investigators to make a precise comparison between these methods. WAIS-R and NART
      showed a comparatively preserved function and were presumed to be useful for the
      evaluation of the baseline of cognitive function in preoperative patients. RBANS
      demonstrated a slight decrease in memory and attention in those patients and was
      expected to be useful to detect the cognitive dysfunction when compared with WAIS
      R and NART.

PMID- 16986675
TI  - [Complex regional pain syndrome type I induced by phenobarbital].
AB  - Complex regional pain syndrome type I (CRPS-I) requires the presence of regional
      pain and sensory changes associated with findings such as abnormal skin color,
      temperature change, sudomotor activity, or edema, following a noxious event.
      Complex regional pain syndrome type I induced by phenobarbital (PB) is not well
      known, although several reports have strengthened the association between PB and
      CRPS-I. I reviewed the charts of 99 patients treated with PB to assess the
      incidence, clinical characteristics, investigations, dosage and plasma
      concentration of PB, and risk factors in the development of CRPS-I. Six patients
      developed CRPS-I. Pain was severe and allodynia, swelling, discoloration,
      sweating were present in all patients. This syndrome manifested bilaterally in
      some patients. Affected patients included 5 men and 1 woman between the ages of
      52 and 78 (average 64.2 years). A radiograph showed demineralization in one
      patient. Thermography showed temperature differences between affected and
      unaffected limbs, although in a few patients the differences were little because
      of bilateral affected limbs. 99Technetium methlyene diphosphonate bone scan
      showed increased periarticular changes in most of the patients. The patients
      developed CRPS-I at 9.7 weeks (average) after PB was begun. The average time was
      7.5 months between CPRS-I and PB reduction. Neither sympathetic ganglion blockade
      nor physical therapy was effective. Treatment of CRPS-I consists of PB reduction
      and prednisone and/or Neurotropin. In all patients clinical symptoms and signs
      such as pain and edema, and range of motion of their shoulders were improved
      after PB discontinuation. One patient was followed longitudinally, documenting
      improvement following discontinuation, reexacerbation with PB rechallenge, and
      remission once more when PB were discontinued. The higher incidence should depend
      on the coexistence of separate risk factors such as age and PB dosage.
      Recognition of CRPS-I induced PB, early diagnosis, and withdrawal of PB are
      important for symptomatic relief and improvement of QOL.

PMID- 16986676
TI  - [Two case mimicking cerebral tuberculoma in MRI diffusion weighted-images with
      difficult preoperative diagnosis].
AB  - Two cases with a high signal intensity core with laminar structure based on
      diffusion weighed-images (DWI) mimicking intracerebral tuberculoma were herein
      reported. Both patients were suspected to have pulmonary tuberculosis in their
      past history and/or based on chest X-ray findings. DWI demonstrated a high signal
      intensity core with laminar structure, thus suggesting the presence of an
      intracerebral tuberculoma. As initial therapy, both patients received anti
      tuberculous drugs, however, their symptoms did not improve, and the lesions were
      observed to have increased in MRI. As a result, a biopsy was carried out to
      clarify the nature of the disease. A pathological examination showed the former
      to be a brain abscess while the latter was metastatic carcinoma. In such cases
      mimicking intracerbral tuberculoma based on DWI, anti-tuberculous drugs are first
      treatment of choice, however, a biopsy should be performed as early as possible
      if the medication dose not show a significant response.

PMID- 16986677
TI  - [Two cases of myelitis associated with Sjogren syndrome without xerosis:
      characteristic MRI findings].
AB  - We report two cases of myelitis associated with Sjogren syndrome without xerosis.
      Case 1: A 30-year old woman developed dysesthesia on both upper extremities and
      weakness of the right arm. A T2-weighted MRI examination showed a high-intensity
      signal and a swollen lesion between the first and seventh cervical vertebral
      levels. She was diagnosed as having primary Sjogren syndrome based on the
      positive finding of a Saxon test, typical salivary gland scintigraphy findings,
      and an elevated anti-SS-A antibody titer. We suspected that her myelitis was
      associated with Sjogren syndrome and treated her using steroid therapy. Although
      her symptoms were alleviated, her myelitis relapsed at the same location after
      the cessation of steroid therapy. Case 2: A 31-year-old woman developed
      dysesthesia on her neck and both upper extremities and exhibited tonic spasm. A
      T2-weighted MRI examination showed a high-intensity signal and a swollen lesion
      between the first and sixth cervical vertebral levels. She was diagnosed as
      having primary Sjogren syndrome based on the positive findings of a Rose Bengal
      test, a Schirmer's test, and a Saxon test as well as typical salivary gland
      scintigraphy findings and elevated titers of anti-SS-A and anti-SS-B antibodies.
      We suspected that her myelitis was associated with Sjogren syndrome and treated
      her using steroid therapy. Her symptoms improved after steroid therapy. Based on
      these two cases, we concluded that MRI findings for myelitis associated with
      Sjogren syndrome are characterized by a swollen lesion of more than three
      vertebral segments in length, and the relapse tends to occur at the same
      location.

PMID- 16986678
TI  - [A case of amyotrophic lateral sclerosis presenting as motor aphasia in its early
      stage].
AB  - A 76-year-old right-handed woman complained of speech disturbance and difficulity
      of singing was admitted to our hospital. Examination showed motor aphasia and
      mild cognitive impairment. After she was discharged, dementia and weakness of the
      extremities had rapidly progressed. She was readmitted eight month after the
      first visit, when she was almost abulic, her skeletal and bulbar muscles were
      remarkably atrophic, and hyperreflexia of the extremities were seen.
      Electromyographcal study showed neurogenic pattern. These findings suggest
      amyotrophic lateral sclerosis (ALS) with dementia. Pathological findings were
      atrophy at the anterior horn of the spinal cord. The brain was diffusely
      atrophic. The extent of degenerative change was not lateralized. This case is a
      discriminative type of ALS with dementia, that its first symptom is motor
      aphasia.

PMID- 16986679
TI  - [Coexistence of hypertensive brainstem encephalopathy and acute ischemic stroke
      in the posterior cerebral artery territory].

PMID- 16986680
TI  - [Two cases of lateral medullary infarctions presenting with axial lateropulsion].

PMID- 16986681
TI  - [Surgical treatment for clinical stage II and III small cell lung cancer
      patients].
AB  - To evaluate a surgical resection in multidisciplinary treatment for clinical
      stage (c-stage) II and III small cell lung cancer (SCLC) patients, we examined
      the postoperative prognosis concerning in 18 patients who underwent complete
      surgical resection. Five-year survival rate of 8 c-stage II and 10 c-stage III
      patients showed 62.5% and 46.7%, respectively. Of these, 7 patients underwent
      preoperative induction chemotherapy resulting in down-staging to c-stage 0-I, and
      their survival rate at 5 years after sugery was as good as 68.6%. However, in 4
      (57.1%) of 7 patients, tumor cells proved to be alive by pathological assessment
      of lymph nodes. As a consequence, it was suggested that surgery for c-stage II
      and III SCLC patients is a meaningful treatment considering their prognoses. In
      particular, even though the patients show a favorable response of preoperative
      chemotherapy, to completely eliminate remnant tumor cells, a surgical resection
      may be necessary.

PMID- 16986682
TI  - [Reconstruction of neck vessels in endovascular repair of aortic arch aneurysms].
AB  - We report 6 cases of aortic arch aneurysms necessitating reconstruction of the
      neck vessel during stent-graft (SG) placement. All patients were male and their
      average age was 75 years. The proximal landing zone was zone 0 in 2, zone 1 in 2,
      and zone 2 in 2 patients. The left subclavian artery (LSCA) was revascularized in
      every case; using left common carotid artery (LCCA)-LSCA bypass in 3, axillo
      axillary artery bypass in 2, and LSCA transposition in 1. Prophylactic LCCA
      revascularization was done in 2 in which obstruction of LCCA by SG was
      anticipated. The proximal portion of LSCA from the origin of the vertebral artery
      was ligated in 3, and divided in 1. Two types of SG were used; Z stent in 1 and
      Matsui-Kitamura stent in 5. There was no hospital death or perioperative stroke.
      In the patient with Z stent, SG could not be deployed because of kinking of the
      delivery system. This patient subsequently underwent surgical SG placement under
      hypothermic circulatory arrest. In the other 5, SG was deployed without any type
      of endoleak. Postoperative complication included incomplete phrenic nerve palsy
      in 1. Prophylactic bypass for LCCA was divided because SG did not obstruct the
      antegrade flow of LCCA. Revascularization of neck vessels can be performed with
      low morbidity in endovascular repair of aortic arch aneurysms.

PMID- 16986683
TI  - [Pulmonary embolectomy for acute massive pulmonary thromboembolism after failure
      of thrombolytic therapy].
AB  - Acute massive pulmonary thromboembolism (PTE) is associated with an exceptionally
      high mortality rate and results in death if not diagnosed early and treated
      properly. We observed 3 cases of acute massive PTE. One of the patients had
      undergone a surgery for femoral neck fracture. Ten days postoperatively, she
      developed severe dyspnea with hypoxia, and computed tomography (CT) pulmonary
      angiography confirmed the PTE diagnosis. She then had cardiac arrest when
      catheter examination. Although emergency surgical thrombectomy was successful
      with good postoperative hemodynamic stability and oxygenation, the patient did
      not recover from the unconsciousness caused by preoperative ischemic brain
      damage. Subsequently, she died 6 months after surgery. Of the 3 patients, 2
      suffered from right ventricular dysfunction without hemodynamic instability. They
      underwent open thrombectomy after the failure of conservative treatment with a
      systemic injection of urokinase. Both patients demonstrated a good clinical
      course and were discharged from hospital in a good general condition 22 and 28
      days postoperatively. Herein, we review the current literature on PTE treatment.
      We concluded that an aggressive surgical intervention might be preferred to
      thrombolytic therapy for PTE patients with massive thrombosis and progressive
      right ventricular dysfunction.

PMID- 16986684
TI  - [Embolism of the lower limb caused by native aortic valve thrombosis].
AB  - Native aortic valve thrombosis is an uncommon event with heart valve disease,
      during cardiac catheterization, bacterial endocarditis, or a hypercoagulative
      state as in antiphospholipid antibody syndrome. We report a case of thrombus
      formation on a native aortic valve, which was found by the transesophageal
      echocardiography during thrombectomy of the lower limb. We supposed that the
      atheromatous plaque of aortic valve was related to thrombus formation.

PMID- 16986685
TI  - [Intermediate results of aortic valve replacement using 19 mm bioprosthetic
      valve].
AB  - Pre- and postoperative hemodynamic parameters and activity of daily life were
      reviewed to estimate the effectiveness of the valve in 12 cases of single aortic
      valve replacement (AVR) using 19 mm bioprosthesis. All implanted prostheses were
      stented-valves. Carpentier-Edwards pericardial valve was used in 7 cases and
      Mosaic valve in 5. Left ventricular mass index (LVMI) significantly decreased
      from 167 +/- 36 to 133 +/- 27 g/m2 in the early postoperative period, and to 115
      +/- 24 g/m2 in the intermediate phase. However, postoperative LVMI remained
      higher in patients with body surface area (BSA) over 1.5 m2 than in those under
      1.5 m2. Postoperative activity indicated by New York Heart Association (NYHA)
      grade significantly improved from 2.3 +/- 1.1 to 1.4 +/- 0.5. These results
      indicates usefulness of 19 mm bioprosthetic valve for reducing left ventricular
      hypertrophy and improving activity, especially in patients with BSA smaller than
      1.5 m2.

PMID- 16986686
TI  - [Mitral valve plasty through right thoracotomy with submammary skin incision].
AB  - A 30-year-old female with congestive heart failure was referred to our hospital
      and massive mitral regurgitation was detected on the echocardiography. She was a
      mother of 2 infants, and wished early recovery from surgery, cosmetic
      consideration to skin incision and future pregnancy. Her mitral valve was
      successfully repaired through right thoracotomy with submammary skin incision.
      Postoperative transthoracic Doppler echocardiography revealed no mitral
      regurgitation. The patient recovered uneventfully and was discharged on the 8th
      postoperative day. And she has been drug-free since then.

PMID- 16986687
TI  - [New method for preparing proximal anastomotic system].
AB  - Heartstring is a useful device. However, the device failure at the time of
      loading the seal into the delivery device is a troublesome issue. To avoid this
      problem, we invent a new method using 2 tourniquets made of 5 mm-wide woven
      Teflon tapes and plastic tubes. Using our method, the loading procedure became
      easier and more reliable.

PMID- 16986688
TI  - [A study of high-resolution computed tomography (HRCT) findings of resected small
      pulmonary nodules 2 cm or less in diameter with reference to the malignant
      nature].
AB  - To identify the characteristics of peripheral small lung mass lesions on high
      resolution computed tomography (HRCT) and discriminate between malignant and
      benign, 223 mass lesions 2 cm or less resected surgically were evaluated about
      following points. 1) Density : 90.7% of lesions with mixed solid and ground-glass
      opacity (GGO) components were adenocarcinomas. Pure GGO lesions without scale
      down between several months were all adenocarcinomas or atypical adenomatous
      hyperplasia (AAH). Thereby, patients with these findings are good candidates for
      surgical resection. 2) Spicular or pleural indentation :75.2% (88 of 117 cases)
      of adenocarcinomas and all squamous cell carcinomas (18 cases) showed these
      findings, but 26.6% (41 of 154 cases) of positive cases were benign lesion (non
      specific inflammation, mycobacterisis, and so on). Accordingly, they are not
      peculiar to malignancy. 3) Satellite lesion : all lesions with this one showed
      benign, therefore it was thought that this finding could exclude malignant
      lesion. Thus, recognition of certain characteristics at HRCT can be helpful in
      discrimination between small malignant mass and benign mass.

PMID- 16986689
TI  - [Successful surgical management of papillary muscle rupture following acute
      myocardial infarction in an elderly patient].
AB  - Papillary muscle rupture is rare but catastrophic complication of acute
      myocardial infarction. We report a 91-year-old woman who underwent successful
      management of papillary muscle rupture following acute myocardial infarction. She
      was transferred to our hospital because of severe pulmonary edema and cardiogenic
      shock. Echocardiography revealed severe mitral valve regurgitation due to total
      rupture of anterolateral papillary muscle. After intubation, intraaortic balloon
      pumping (IABP) and percutaneous cardiopulmonary support (PCPS) insertion, mitral
      valve replacement was successfully performed. She was discharged 134 days after
      operation. In papillary muscle rupture deteriorating hemodynamics, early
      diagnosis and immediate cardiopulmonary support are required before surgical
      treatment. She was, to the best of our knowledge, the oldest among the reported
      cases of successful surgical treatment of papillary muscle rupture in Japan.

PMID- 16986690
TI  - [Successful removal of aberrant needles in the pericardium and lung].
AB  - A 28-year-old woman who had been diagnosed as schizophrenia was admitted to our
      hospital, complaining of chest pain. Her chest X-ray demonstrated 9 foreign
      bodies in the pericardium, lung and others. Her chest computed tomography (CT)
      confirmed needle-like shadows in the pericardium and lung. They were diagnosed as
      aberrant needles, and surgically removed. The intrapulmonary aberrant needle was
      removed with video-assisted thoracoscopic surgery. Aberrant needle in pericardium
      or lung should be removed surgically, because it is very dangerous.
      Intraoperative chest X-ray is always necessary before closing the wound to avoid
      leaving the residual fragments.

PMID- 16986691
TI  - [Acute aortic regurgitation by spontaneous rupture of a fibrous strand in
      fenestrated aortic valve; report of a case].
AB  - Although fenestration of the aortic valve cusps is a common anatomic finding, it
      rarely causes aortic regurgitation. We describe acute aortic regurgitation by
      spontaneous rupture of a fibrous strand in fenestrated aortic valve. A 65-year
      old man was referred with sudden onset of dyspnea and cough. He diagnosed acute
      heart failure due to severe aortic valve regurgitation. After medical therapy,
      the aortic valve replacement was performed. Operative findings reviewed that a
      fibrous strand in the fenestrated non-coronary cusp was ruptured, which caused
      severe aortic regurgitation. Pathological examination showed the myxomatous
      degeneration. The postoperative course was uneventful, and the patient was
      discharged on postoperative day 11 with good health.

PMID- 16986692
TI  - [Acute type A aortic dissection with partial disruption of the right coronary
      ostium; report of a case].
AB  - A 64-year-old man with a history of hypertension was admitted to another
      hospital, presenting with sudden chest pain. Although his symptoms resolved after
      admission, chest computed tomography (CT) revealed acute type A aortic
      dissection, and he was referred to our hospital for surgery. On arrival, his
      hemodynamic status was stable. Electrogram showed no ST-T change, and
      transthoracic echocardiography demonstrated pericardial effusion, mild aortic
      regurgitation and good left ventricular wall motion. We immediately decided on an
      emergency operation. Commencing a median sternotomy, the pericardial cavity was
      found to be filled with old blood. Standard cardiopulmonary bypass was instituted
      with right atrial drainage and right femoral arterial return, and with right
      upper pulmonary venous venting. When antegrade cold blood cardioplegia was
      selectively administered, we noticed the partial disruption of the upper aspect
      of the right coronary ostium. The right coronary sinus was resected in a scallop
      shape. Partial aortic root remodeling using a trimmed tube graft and coronary
      artery bypass grafting to the right coronary artery with saphenous vein were
      performed under deep hypothermic circulatory arrest. Weaning from cardiopulmonary
      bypass was not difficult. The postoperative course was uneventful.

PMID- 16986694
TI  - [Pulmonary benign metastasizing leiomyoma from uterine myoma; report of a case].
AB  - A 46-year-old female with benign metastasizing leiomyoma was reported. The
      patient had undergone a lobectomy of thyroid for adenomatous goiter at the age of
      30, and a myomectomy for uterine myoma and a modified radical masmectomy for
      breast cancer at the age of 32. The chest X-ray on health screening revealed
      multiple nodules in the bilateral lung. Computed tomography (CT) revealed 6
      nodules in the right side and 3 nodules in the left side of the lung. The tumors
      of the right lung were resected under thoracoscopic surgery. Pathologically these
      lesions were diagnosed as benign metastasizing leiomyoma. Left lung nodules have
      been followed-up.

PMID- 16986693
TI  - [Thymic carcinoid accompanied by elevation of serum gastrin-releasing peptide
      precursor; report of a case].
AB  - A 74-year-old male was admitted with an abnormal mediastinal shadow. Computed
      tomography (CT) and magnetic resonance imaging (MRI) of the thorax showed an
      anterior mediastinal mass without invasion to the ascending aorta and pulmonary
      artery. In addition, serum gastrin-releasing peptide precursor (Pro GRP) was
      increased (60.6 pg/ml, normal range <46 pg/ml). Video-assisted thoracoscopic
      biopsy demonstrated that the mass was thymic carcinoid. Therefore, median
      sternotomy was performed to facilitate thymectomy, including the tumor with
      partial resection of the left upper lobe and pericardium. The patient received
      mediastinal irradiation postoperatively. The postoperative serum level of Pro GRP
      decreased to the normal limit 6 months later. Although a biological relationship
      between Pro GRP and thymic carcinoid was not proven, it might be useful marker
      for detecting tumor recurrence.

PMID- 16986695
TI  - [pN0 stage IA lung cancer downstaged from pN2 IIIA by induction therapy; report
      of a case].
AB  - A 75-year-old male of adenocarcinoma in non-small cell lung cancer (NSCLC) was
      diagnosed to be p-staged IIIA by a preoperative mediastinoscopy. After the
      induction chemotherapy of cisplatin (80 mg/m2, day 1, 4 weeks, 2 cycles) plus
      docetaxel hydrate (60 mg/m2, day 1, 4 weeks, 2 cycles), we performed lobectomy
      and lymph nodes dissection. The postoperative pathological results showed no
      metastasis of the resected lymph nodes. The postoperative stage has been down to
      be pN0 IA from pN2 IIIA. After the adjuvant therapy of docetaxel hydrate (60
      mg/m2, day 1, 4 weeks, 2 cycles), the postoperative serum carcinoembryonic
      antigen level has been normalized without a recurrence for more than 2 years. A
      pathological staging with a mediastinoscopic diagnosis for the suspected clinical
      IIIA-staged NSCLC should bring us a good assessment of the induction therapy.

PMID- 16986696
TI  - [Cavitating pleomorphic carcinoma of the lung; report of a case].
AB  - We report a case of a previously healthy 76-year-old male with cavitating
      pleomorphic carcinoma of the lung. He was admitted because of an abnormal lung
      shadow on chest X-ray. Computed tomography (CT) showed a well-demarcated nodular
      shadow within thin-walled cavity in the right upper lobe. Because the lesion was
      revealed as adenocarcinoma by transbronchial lung biopsy, right upper lobectomy
      was performed. By histopathologic examination of the resected specimen, the
      nodule contained a component of spindle cell features and the cavity wall was
      composed of adenocarcinoma. The final diagnosis was pleomorphic carcinoma.
      Postoperative course has been uneventful for 12 months after surgery.

PMID- 16986697
TI  - [Longitudinal analysis of age at onset and initial symptoms in patients with
      amyotrophic lateral sclerosis].
AB  - To investigate the longitudinal changes in age at onset and the initial symptom
      of patients with sporadic amyotrophic lateral sclerosis (ALS), we performed a
      single hospital-based retrospective study over the past 38 years. A total of 280
      sporadic ALS patients (169 men and 111 women) hospitalized in our department
      between 1965 and 2003 were investigated in this study. The clinical features
      including age at onset and the initial symptom of these patients were obtained
      from medical records. All the patients underwent an intensive diagnostic
      evaluation including electrophysiological examination, laboratory examinations of
      blood and cerebrospinal fluid, and neuroimagings of the brain and spinal cord to
      exclude other conditions similar to ALS. The mean age at onset was 58.3 +/- 11.3
      years and age at onset significantly increased at the rate of 0.459 years per
      year (r = 0.406, p< 0.001). The percentage of patients whose age at onset was >
      or = 70 years has increased from 3.0% (1980-1984) to 31.1% (2000-2003). To
      investigate the initial symptom of senile-onset ALS, patients whose age at onset
      was > or = 70 years were analyzed. The percentages of bulbar palsy-onset patients
      with onset in terms of age were 62.5% (30/48 patients; > or = 70 years) and 23.3%
      (54/232 patients; <70 years). The odd ratio for bulbar palsy was 5.40 (95%
      confidence interval, 2.79-10.44). Taken together, our study demonstrates that the
      ratio of senile-onset ALS has significantly increased, and that there were more
      bulbar palsy-onset patients among the patients.

PMID- 16986698
TI  - [Clinical characteristics of elderly Japanese patients with amyotrophic lateral
      sclerosis; with special reference to the development of respiratory failure].
AB  - OBJECTIVE: To clarify the characteristics of elderly-onset amyotrophic lateral
      sclerosis (ALS). SUBJECTS AND METHODS: We analyzed the pattern of progression of
      clinical symptoms and respiratory dysfunction in 26 sporadic ALS patients (19
      men, 7 women; mean age 73.2 +/- 6.0 years) with onset at age 65 years or older (E
      ALS). We compared the results with those of 28 ALS patients (20 men, 8 women;
      53.7 +/- 7.6 years) with younger onset ALS (Y-ALS). RESULTS: Among E-ALS
      patients, the bulbar palsy type (BP) was the most common (11 patients, 42%)
      followed by the respiratory failure type (RF) (7 patients, 27%). In contrast,
      upper extremity type (UE) was the most common (14 patients, 50%) in Y-ALS
      patients. Mean vital capacity percentage (%VC) at the initial examination was
      71.1 +/- 20.4% (vital capacity (VC): 2.12 +/- 0.85 L) in all E-ALS patients, 64.5
      +/- 14.5% in BP, 58.1 +/- 5.1% in RF, 94.4 +/- 11.1% in lower extremity type
      (LE), and 73.9 +/- 30.2% in UE. In all Y-ALS patients, %VC was 90.1 +/- 14.0%
      (2.94 +/- 0.57 L). The initial % VC value in E-ALS was significantly lower than
      that in Y-ALS (p < 0.01). VC was lower in RF and BP among E-ALS patients. It was
      also lower in BP E-ALS patients than in BP Y-ALS patients. Mean period from
      initial symptom until first examination was significantly shorter in RF in both
      groups, followed by BP. Twenty-two patients with E-ALS and 26 with Y-ALS died
      from respiratory failure. Four patients with E-ALS and 2 with Y-ALS required a
      mechanical ventilator. The mean period until death or ventilation support was
      20.9 +/- 10.4 months in E-ALS, and 38.8 +/- 21.1 months in Y-ALS. Significantly
      shorter survival was observed in E-ALS than Y-ALS (p<0.01). In E-ALS patients,
      the mean period until death or ventilation support was 21.4 +/- 9.1 months with
      BP, 10.3 +/- 7.6 months with RF, 29.8 +/- 4.0 months with LE, and 29.3 +/- 5.4
      months with UE. This period was significantly shorter in RF patients in both
      groups, followed by BP patients (p< 0.05, 0.01). Time until death or ventilation
      support was significantly shorter in BP and UE patients with E-ALS than in those
      with Y-ALS (p< 0.05). CONCLUSION: In regard to the progression of respiratory
      function deterioration, early % VC was lower in E-ALS than in Y-ALS patients, and
      the period until VC fell below 1 L was shorter. The period until death was
      particularly short in elderly BP and RF patients, suggesting the possibility that
      the duration until death from respiratory failure is shorter in E-ALS, because of
      a decrease in respiratory reverse capacity that accompanies age.

PMID- 16986699
TI  - [Case presenting both clinical features of progressive supranuclear palsy and
      amyotrophic lateral sclerosis].
AB  - A 70-year-old Japanese male farmer, born and living in Kyoto prefecture,
      developed gait disturbance, with tendency to fall at age 68, and muscle atrophy
      and weakness of the right shoulder and arm a year and half later. All symptoms
      have been progressive ever since. The patient manifested marked dementia,
      parkinsonism associated with limitation of ocular movements in all directions
      with slow saccade, loss of startle reflex, asymmetric muscle atrophy and weakness
      in shoulder girdles and upper limbs with hyperreflexia, and positive Babinski
      reflexes. The needle electromyogram showed evidence of active denervation. Brain
      MRI showed cortical atrophy in the frontal and temporal lobes, and midbrain
      tegmentum. Cerebral blood flow image on SPECT suggested hypoperfusion in the
      frontal, temporal and parietal cortices and basal ganglia bilaterally. Thus, it
      is most likely that the present case suffered from clinical features of
      amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy at the
      same time. Relation to the ALS/Parkinsonism/Dementia complex reported from Kii
      peninsula and Guam was discussed.

PMID- 16986700
TI  - [Case of intracranial hypotension responsive to oral prednisolone].
AB  - A 31-year-old female patient with headache and nausea was admitted to our
      hospital, although there were no apparent neurological abnormalities except
      headache. Cerebrospinal fluid (CSF) pressure was 40 mmH2O on the first lumbar
      puncture and CT showed some fluid in the left maxillary sinus. She gradually
      developed orthostatic headache despite antibiotics, hydration and analgesics. MRI
      showed diffuse meningeal thickening and enhancement. CSF pressure was 0 mmH2O on
      the second lumbar puncture and RI cisternography demonstrated early excretion to
      the kidneys. She was diagnosed with intracranial hypotension due to CSF leakage.
      An autologous 10ml blood patch on the lumbar epidural space did not relieve the
      orthostatic headache. However, headache disappeared one day after oral intake of
      40mg prednisolone. During the next three months, oral prednisolone was tapered
      off. Three months after the onset of the illness, MRI did not show either
      meningeal thickening or enhancement. We concluded that oral prednisolone was
      effective in a case of intracranial hypotension.

PMID- 16986701
TI  - [Case of juvenile parkinsonism in pregnancy].
AB  - A 29-year-old woman with two sons developed a rest tremor and motor slowness in
      her right limbs. She was diagnosed as Parkinson's disease (PD) and was treated
      with anti-cholinergic drugs. After three years of taking a dopamine agonist
      (cabergoline, 4 mg per day), she became pregnant. The patient and her husband
      decided to have an abortion because they worried that the cabergoline might have
      harmed the fetus. The patient hoped to prepare for future planned birth, so we
      canceled the cabergoline and gradually increased her carbidopa/levodopa dose. Her
      motor disability gradually worsened during the pregnancy, and she developed
      prominent bradykinesia while taking a high dose of carbidopa/levodopa (1,000 mg
      per day) and a continuous infusion of levodopa. A cesarean section was performed,
      and the patient gave birth to a healthy baby. After the delivery, she was treated
      with pramipexole (2 mg per day), and her bradykinesia decreased. The initial anti
      PD medication schedule for fertile female PD patients should be carefully
      considered to lessen the harm to the fetus, especially during organogenesis.
      Motor disability may worsen during pregnancy, and appropriate childcare support
      should be prepared.

PMID- 16986702
TI  - [Case of leptomeningeal carcinomatosis effectively treated with intrathecal
      chemotherapy using ventriculoperitoneal shunt].
AB  - A 70-year-old man presented with dizziness, headache and hearing loss. He was
      admitted to our hospital because of increasing unsteadiness of gait. Magnetic
      resonance imaging of the brain revealed meningeal thickening with enhancement.
      The lumbar puncture revealed high opening pressure. The cerebrospinal fluid
      showed pleocytosis, high carcinoembryonic antigen (CEA) concentration, and
      presence of neoplastic cells, leading to the diagnosis of leptomeningeal
      carcinomatosis. Systemic investigation for primary neoplasm identified a Bormman
      type 3 gastric cancer (papillary adenocarcinoma with micropapillary pattern).
      Except for the meninges, no metastatic lesions could be detected. A
      ventriculoperitoneal shunt (Codman Hakim Programmable Valve) was placed for
      management of intracranial hypertension and intrathecal chemotheray. He was
      started on oral S-1 (TS-1) combined with intrathecal methotrexate injection using
      the VP shunt reservoir. In two weeks, headache and hearing loss completely
      disappeared and gait disturbances started to improve. CSF findings also improved
      remarkably with disappearance of neoplastic cells and almost normalization of
      CEA. For the next five months, he was well on oral S-1 and monthly intrathecal
      chemotherapy, being able to walk using a walker and to stay at home. He
      subsequently developed posterior cortical symptoms such as prosopagnosia and
      cortical blindness and gradually lapsed into coma. He died from pneumonia one
      year after the onset of neurological symptoms. At autopsy, primary gastric cancer
      was found but much reduced in size. No peritoneal metastasis could be found. In
      the brain, leptomeningeal carcinomatosis involved the occipital lobes, the base
      of the temporal lobe, and the cerebellum. We suggest that intrathecal
      chemotherapy using ventriculoperitoneal shunt with programmable valve system
      could be an effective method for the treatment of meningeal carcinomatosis.

PMID- 16986703
TI  - [Case of neuro-Behcet disease with homonymous quadrantanopsia due to an
      inflammatory lesion involving the lateral geniculate body].
AB  - We report a rare case of a 57-year-old woman of neuro-Behcet disease with
      homonymous quadrantanopsia due to an inflammatory lesion involving the lateral
      geniculate body. She had oral and genital ulcers since 1983, and uveitis since
      May 1985. She received diagnosis of incomplete Behcet disease and was prescribed
      cyclophosphamide since June 1985. After the treatment, she recovered completely
      from uveitis in July 1985. Painful subcutaneous nodules appeared in her right leg
      on June 21, 2004 and she had a high fever, headache and left visual disturbance
      on June 29, 2004. Therefore, she was admitted to our hospital on July 1, 2004.
      Physical and neurological examination showed erythema nodosum in the right lower
      extremity and left lower homonymous quadrantanopsia. Laboratory findings on
      admission showed leucocytosis, increased erythrocyte sedimentation rate and C
      reactive protein, and positive HLA-B51. Cerebrospinal fluid analysis showed
      pleocytosis and a markedly high level of protein and interleukin-6. Brain
      magnetic resonance imaging (MRI) of T2-weighted images showed high intensity
      lesions in the circumference of the caudal thalamus, optic radiations, and right
      occipital cortex. T1-weighted images with gadolinium enhancement showed an
      enhanced lesion in the circumference of the right lateral geniculate body. From
      these results, she was diagnosed as having an acute relapsing phase of neuro
      Behcet disease and she received steroid pulse therapy. Immediately after steroid
      pulse therapy, she received high-dose prednisolone which was gradually tapered.
      Brain MRI after treatment showed a high intensity lesion in the right lateral
      geniculate body. Homonymous quadrantanopsia remained nearly unchanged.

PMID- 16986704
TI  - [Facial chorea and hemichorea due to cardiogenic cerebral embolism in the cortex
      and subcortical white matter].
AB  - A 62-year-old man was admitted to our hospital because of suddenly developed
      bilateral facial chorea and left-sided hemichorea. He had neither hemiparesis nor
      sensory disturbance. Diffusion-weighted magnetic resonance images of the brain
      showed acute cortical and subcortical infarctions at the right insula, frontal,
      temporal and parietal lobes. Tiapride hydrochloride was administered for his
      chorea. The chorea disappeared on the next day. We diagnosed him as cardiogenic
      cerebral embolism because he had a paroxysmal atrial fibrillation. We supposed
      that his chorea was induced by interruption of excitatory output from cerebral
      cortex to striatum and subthalamic nucleus. Contralateral cortical and
      subcortical infarction must be considered when a patient suddenly develops
      hemichorea.

PMID- 16986705
TI  - [Sweetness dysgeusia in a case of SIADH caused by lung carcinoma].
AB  - A 56-year-old woman, with dysgeusia in which nearly all food was felt as sweet,
      was admitted to our hospital seeking for treatment. Serum sodium concentration
      was 113 mmol/L, but serum creatinine, zinc, urea nitrogen, and potassium, as well
      as blood glucose, were all within normal ranges. Dysgeusia disappeared when serum
      sodium level was normalized, but recurred when hyponatremia relapsed. She was
      diagnosed as having large cell lung carcinoma. We considered that the cause of
      hyponatremia was inappropriate secretion of antidiuretic hormone (SIADH) due to
      lung carcinoma. Miraculin is one of taste-modifying substances which fits the
      sweet receptor site and induces a strong sweet taste. We considered that taste
      modifying substances same as miraclin are involved in the pathophysiology of this
      disease.

PMID- 16986706
TI  - [Case of spinal thoracic-lumbar dural arteriovenous fistula with polyneuropathy
      type sensory impairment].
AB  - A 57-year-old man had progressive paresthesias ascending from both legs together
      with paraparesis. Distal paresthesias of the upper extremities developed earlier
      than segmental sensory impairments. At transfer to our hospital, a neurological
      examination detected bilateral lower limb weakness predominant in the distal
      part; severe glove and stocking paresthesias in addition to superficial sensory
      impairment below the Th8 level; and micturition problems. T2-weighted
      thoracolumbar MRI showed a hyperintense spinal cord lesion between Th5 and L1. At
      the L4 level, a spinal arteriogram showed enlarged and tortuous vessels extending
      from the lumbar artery which drains to the spinal vein. These findings led to the
      diagnosis of spinal dural arteriovenous fistula. Anatomical substrates for this
      sensory impairment may be produced by development from the side to forward parts
      of lesions in the outer circumference of the anterior funiculi, resulting in the
      dominating sensory impairment in the distal parts of the upper extremities.
      Physicians need to be aware of patients who have polyneuropathy-like sensory
      impairment without segmental sensory signs, and must consider the possibility of
      spinal dural arteriovenous fistula.

PMID- 16986707
TI  - [JAK2 mutation in myeloproliferative disorders].

PMID- 16986708
TI  - [Cytomorphology of acute myeloid leukemia and myelodysplastic syndromes].

PMID- 16986709
TI  - [Mutation of the nucleophosmin gene in acute myeloid leukemia].

PMID- 16986710
TI  - [Therapeutic strategies for patients with relapsed acute promyelocytic leukemia].

PMID- 16986711
TI  - [Helicobacter pylori eradication in patients with immune thrombocytopenic
      purpura. A novel therapy?].

PMID- 16986712
TI  - [Thrombotic microangiopathy].

PMID- 16986713
TI  - [Effectiveness of long term administration of humanized anti-interleukin-6
      receptor antibody (tocilizumab) for multicentric Castleman's disease with
      pulmonary involvement].
AB  - A 27-year-old man was admitted to our hospital with the complaint of general
      fatigue. He had cervical and mediastinal lymphadenopathy. Laboratory examination
      revealed anemia, hypergammaglobulinemia, and increased levels of C-reactive
      protein (CRP) and erythrocyte sedimentation rate (ESR). A chest radiograph showed
      opacities in both lung fields. Pathological findings from thoracoscopic
      mediastinal lymph node and lung biopsies were compatible with multicentric
      Castleman's disease (MCD), plasma cell type with pulmonary involvement.
      Chemotherapy combined with radiation therapy resulted in no improvement of his
      lymphadenopathy and inflammatory symptoms. Eight mg/kg humanized anti-human IL-6
      receptor antibody (tocilitumab) was thus administered biweekly. Soon after
      initiating the tocilitumab treatment, the patient's general fatigue disappeared,
      and anemia, CRP, ESR, hypergammaglobulinemia and lymphadenopathy all improved
      remarkably. Further treatment with tocilitumab for two years resulted in
      maintenance of this good response without any severe adverse events, but the
      pulmonary findings showed no obvious improvement. Tocilitumab therapy was
      effective in this MCD patient, however its influence on concurrent lung disease
      needs to be investigated further.

PMID- 16986714
TI  - [Successful treatment with voriconazole for disseminated cutaneous and visceral
      infection by Fusarium solani in a patient with acute myeloid leukemia].
AB  - We report the successful treatment of a disseminated Fusarium infection with skin
      manifestations in a severely neutropenic patient. A 51-year-old man with acute
      myeloblastic leukemia (M4) underwent two courses of remission induction therapy
      with cytarabine and daunorubicin. Despite prophylactic treatment with
      tosufloxacin and micafungin, the patient developed a febrile scrotal ulcer. Eight
      days later, we noted the appearance of painful and diffuse cutaneous nodules and
      a plain chest X-ray disclosed multiple nodular lesions. Microbiological
      examination of the scrotal ulcer revealed infection by Fusarium solani, which was
      also confirmed by both histological and microbiological examination of the skin
      nodules. Although the patient was treated with amphotericin B (AMPH-B), the
      clinical symptoms worsened. After AMPH-B was replaced with voriconazole (VRCZ),
      the patient's symptoms and chest radiographic findings dramatically improved.
      Thus, VRCZ might be an alternative therapy for patients with neutropenia who have
      fusariosis that is refractory or unresponsive to AMPH-B.

PMID- 16986716
TI  - [Recurrent spontaneous regression of aleukemic leukemia cutis in a girl with
      acute monocytic leukemia].
AB  - Aleukemic leukemia cutis is a rare form of leukemia manifestation, defined as a
      skin infiltration of leukemic cells with no evidence of leukemia in the bone
      marrow. A 4-month-old girl was referred to our hospital because of exanthema that
      appeared and regressed repeatedly. Histological examination revealed partial
      infiltration of histiocytic cells in the skin lesion. However, the diagnosis
      could not be made at that time. At 9 and at 13 months old, appearances of
      exanthema similar to the previous time were combined with systemic fever,
      abnormal coagulation tests, and the marked increases of atypical lymphocytes in
      peripheral blood: however, these symptoms resolved spontaneously. At 14 months
      old, deterioration of the exanthema and an increase in the peripheral leukocyte
      counts were observed. Bone marrow aspiration revealed the predominance of
      monocytic blasts (76.4%), and the patient was diagnosed as having acute monocytic
      leukemia (M5b) with leukemia cutis. Complete remission was obtained with standard
      chemotherapy. Six months after the therapy was completed, an extramedullary
      relapse occurred in the inguinal lymph nodes, which was successfully treated with
      allogeneic bone marrow transplantation from an HLA-matched unrelated donor, and
      the patient has been free of disease for two years after the transplantation.

PMID- 16986715
TI  - [Two cases of heparin-induced thrombocytopenia (HIT) and a review of the
      literature].
AB  - We experienced two cases of heparin-induced thrombocytopenia (HIT) which occurred
      during unfractionated heparin treatment. The first patient was a 72-year-old man,
      who was admitted to our hospital because of sudden onset dyspnea in January 2000.
      He was diagnosed as having a pulmonary embolism and heparin was started. Nine
      days later, progressive embolization of the pulmonary artery and femoral vein was
      found and thrombocytopenia (platelet count 20 x 10(9)/l) was observed 14 days
      after that. Cessation of heparin and administration of argatroban resulted in
      progressive normalization of the platelet count. The second patient was a 62-year
      old woman, who was admitted to our hospital in April 2001, with the chief
      complaint of sudden onset dyspnea. She was diagnosed as having acute left-sided
      heart failure and heparin was started. Fifteen 15 days later, thrombocytopenia
      (platelet count 17 x 10(9)/l) was observed. Cessation of heparin resulted in
      normalization of the platelet count. Both cases were positive for anti-heparin
      platelet factor 4 (PF4) antibody. Here we report on the clinical course of two
      cases of HIT with a review of the literature.

PMID- 16986717
TI  - [Acute monoblastic leukemia with tetrasomy 8].
AB  - Tetrasomy 8 is a rare chromosomal abnormality in acute leukemia, and it has
      recently been considered as a poor prognostic factor. A 20-year-old woman was
      admitted because of purpura on the upper and lower limbs in February 2002. On
      admission, her leukocyte count was 6.5 x 10(9)/l with 66% of blasts, the
      hemoglobin level was 11.2 g/dl, and the platelet count was 101 x 10(9)/l. The
      bone marrow aspirate contained 85.6% of peroxidase-negative, alpha-naphthyl
      butyrate esterase-positive, and CD4+ CD56+ blast cells. Karyotypic analysis of
      the bone marrow cells showed 48, XY, + 8, + 8[17]/47, XY, +8[3]. The patient was
      diagnosed as having AML (M5a), and treatment with daunorubicin (70 mg x 5 days)
      and cytosine arabinoside (150 mg x 7 days) resulted in a complete remission. She
      relapsed four months later, however, with an extramedullary tumor in T12.
      Remission could not be achieved, and the patient underwent allogeneic peripheral
      blood stem cell transplantation from her HLA-identical mother. Her clinical
      course was almost uneventful except for a phlegmon in the right leg, but on day
      49 a relapse occurred, and she died of acute renal failure on day 73. This case
      strongly illustrates the characteristic of tetrasomy 8 as a poor prognostic
      factor in acute leukemia.

PMID- 16986718
TI  - [Bortezomib-induced tumor lysis syndrome with a remarkable elevation of LDH in a
      case of relapsed and therapy-resistant multiple myeloma].
AB  - A 60-year-old female patient with a therapy-resistant Bence-Jones (BJ) lambda
      type multiple myeloma was treated with bortezomib. She had been treated with
      tandem autologous stem cell transplantations and achieved complete remission
      before her disease relapsed. Sixteen hours after the first administration of
      bortezomib, an episode of fever, slight consciousness disturbance and vomiting
      occurred, which was accompanied by a remarkable elevation of LDH (3608 IU/l).
      Serum levels of creatinine, uric acid, and AST were also transiently elevated.
      Serum interleukin-6 level was also increased after the administration of
      bortezomib. The symptoms disappeared rapidly within 48 hours. Bortezomib at a 25%
      reduced dose was administered again along with dexamethasone 26 days later, which
      caused a moderate increase in LDH levels, but no other symptoms. Further
      treatment caused no increase in LDH. The treatment was very effective and
      eradicated both urinary BJ protein and bone marrow myeloma cells after 8 sessions
      of bortezomib administration. These findings suggest that a bortezomib-induced
      rapid reduction in tumor burden led to tumor lysis syndrome, for which caution is
      needed when treating myeloma patients with this very effective agent.

PMID- 16986719
TI  - [Four cases of pseudothrombocytopenia due to platelet cold agglutinins].
AB  - We report 4 cases of pseudothrombocytopenia due to platelet cold agglutinins.
      Case 1 was a 57 y.o. female whose platelet count was 97 x 10(3)/microl. Case 2
      was a 37 y.o. male with a platelet count of 96 x 10(3)/microl. Case 3 was a 74
      y.o. male with a platelet count of 28 x 10(3)/microl. Case 4 was a 62 y.o. female
      whose platelet count was 34 x 10(3)/microl. The platelet counts in these 4 cases
      were decreased and blood smears showed platelet clumping in blood drawn in a tube
      without anticoagulant just after withdrawal, as well as in blood drawn in a tube
      with anticoagulant. The platelets from these patients agglutinated at a
      temperature below 10 degrees C (case 1 and 4) and 24 degrees C (case 2). The
      immunoglobulin class of the platelet cold agglutinins in cases 1, 2 and 4 was
      IgM. Agglutinated platelets showed no activation marker, such as CD62P, CD63 or
      CD40L, on the surface of the platelets. The target antigen of cold agglutinins
      was GPIIb-IIIa in cases 1 and 2. We considered that the detection of platelet
      agglutination in blood without anticoagulant is important to diagnose
      pseudothrombocytopenia due to platelet cold agglutinins. Although this disease is
      considered to be very rare, we suspect that this disease may be misdiagnosed as
      pseudothrombocytopenia due to the presence of an anticoagulant, and overlooked.

PMID- 16986720
TI  - [Plasmapheresis for fulminant autoimmune hemolytic anemia with rapidly
      progressing disturbance of consciousness].
AB  - A 64-year-old male was diagnosed as having autoimmune hemolytic anemia (AIHA) in
      December 2001. The diagnosis of AIHA was established based on the presence of
      anemia, hyperbilirubinemia, reticulocytosis, positive Coombs test and serum LDH
      elevation. Although he received steroid pulse therapy, disturbance of
      consciousness appeared and the anemia and icterus did not improve. Plasma
      exchange was carried out to eliminate antibodies as an emergency measure. The
      patient's symptoms were ameliorated following four courses of plasma exchange.
      This case represents a case of aggressive AIHA with disturbance of consciousness
      and refractory to conventional corticosteroid therapy. Plasma exchange rapidly
      led to complete remission.

PMID- 16986721
TI  - [AID controls immunoglobulin class switch recombination].

PMID- 16986722
TI  - [Multifunctional sphingolipid, sphingosine (long-chain base) 1-phosphate:
      physiological role, metabolism, and intracellular dynamics].

PMID- 16986723
TI  - [Role and mechanism of action of vitamin A in gut immunity].

PMID- 16986724
TI  - [Steroid 11beta-hydroxylase deficiency--focusing on the CYP11B2/CYP11B1 chimera
      which has been recently discovered as the causing gene--].

PMID- 16986725
TI  - [Emerging roles for the septin family of GTP-binding proteins in mitosis and
      cellular morphogenesis].

PMID- 16986726
TI  - [Various applications of fluorescent proteins for cell biology].

PMID- 16986727
TI  - [Vasohibin, a novel angiogenesis inhibitor ].

PMID- 16986728
TI  - [Activation mechanism of an anti-viral ribonuclease, RNase L].

PMID- 16986729
TI  - [Keratin expression in cultured non-epithelial cells].

PMID- 16986730
TI  - [Charismatic adults for children with developmental disorders].

PMID- 16986731
TI  - [Acute flaccid paralysis during febrile illness in an infant].

PMID- 16986732
TI  - [Sleep and brain function].
AB  - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) catalyzes the isomerization
      of PGH2, a common precursor of various prostanoids, to produce PGD2, a potent
      endogenous somnogen. L-PGDS is localized in the leptomeninges, choroid plexus,
      and oligodendrocytes of the central nervous system. PGD2 is proposed to be a
      major humoral sleep-inducing factor accumulated in the brain during wakefulness.
      PGD2 stimulates DP, receptors localized in the basal forebrain and increases the
      local extracellular concentration of adenosine, which activates A2A receptor
      possessing neurons in the basal forebrain and/or ventrolateral preoptic area
      (VLPO). The intracerebroventricular infusion of PGD2 or adenosine A2A receptor
      agonists induces non-REM sleep and increases the expression of fos protein in
      VLPO. The activation of VLPO neurons is associated with decreased fos expression
      in the histaminergic tuberomammillary nucleus (TMN), one of the arousal centers.
      The GABAergic inhibition of TMN is involved in non-REM sleep induction by PGD2 or
      adenosine A2A receptor-agonists. The neural network between VLPO and TMN is
      considered to play a key role in the regulation of vigilance states.

PMID- 16986733
TI  - [Evaluation of social functioning ability of disabled children].
AB  - Since 1999, we have been trying to establish a reliable method for evaluating
      social functioning ability (SFA) of physically handicapped children, in
      cooperation with the Project of Comprehensive Study of Disability, Social Health,
      and Welfare supported by the Ministry of Health, Labor and Welfare, Japan. In
      this study, we investigated the reliability and accuracy of the 4th edition of
      "The Evaluation of SFA". This evaluation consists of 40 items in 15 areas. We
      examined 45 disabled patients (26 males and 19 females) aged 12-27 years (mean
      age, 16 years). The reliability was checked by agreement of evaluations of the
      same patient carried out by two examiners. The results showed good reliability
      (kappa value of 0.42). According to the results of questionnaires, 97% of the
      examiners regarded this evaluation to be useful. Although the score of SFA
      correlated with intelligent quotient/development quotient, the score did not
      correlate with motor disability level. We hope that this evaluation will be
      widely used to upgrade SFA of disabled children.

PMID- 16986735
TI  - [Saccadic eye movements in children with reading disorders].
AB  - Several reports raised the possibility that dysfunction of saccadic eye movements
      produces reading disorder (RD), although opposite conclusions have also been
      reported. In this study, saccadic eye movements were investigated in 13 forth
      graders with RD and 20 age-matched controls during reading and non-reading tasks.
      Compared to the control group, children with RD showed significantly higher
      incidences of both forward and backward saccadic eye movements in reading tasks,
      while they revealed a significantly lower number of saccadic eye movements in
      response to sequentially moving targets in two types of non-reading tasks. These
      problems, seen in non-reading tasks, suggest that excessive saccadic eye
      movements observed in RD children during reading are not produced by mechanisms
      involved in the language and phonological processes alone, but also those in the
      saccadic eye movement process. Dysfunction in the saccadic eye movements could be
      one of the causal factors that produce RD.

PMID- 16986734
TI  - [Symptomatic hypersomnia due to orexin deficiency in hypothalamic lesions].
AB  - Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy and
      other abnormal manifestations of REM sleep. Recently, it was discovered that the
      pathophysiology of idiopathic narcolepsy-cataplexy is linked to orexin ligand
      deficiency in the brain and cerebrospinal fluid. Orexin neurons localize in the
      posterior hypothalamic area, which was previously described as "waking center" by
      von Economo in 1920s. Hypersomnia due to orexin ligand deficiency can also occur
      during the course of other neurological conditions, such as hypothalamic tumor,
      encephalopathy and demyelinating disorder (i.e. symptomatic hypersomnia). We
      experienced 8 pediatric cases with symptomatic hypersomnia. These cases were
      diagnosed as brain tumor (n = 2), head trauma (n = 1), encephalopathy (n = 1),
      demyelinating disorder (n = 3) and infarction (n = 1). Six pediatric cases with
      orexin measurements from the literatures were additionally included and total 14
      cases were studied. Although it is difficult to rule out the comorbidity of
      idiopathic narcolepsy in some cases, a review of the case histories reveals
      numerous unquestionable cases of symptomatic hypersomnia. In these cases, the
      occurrences of the hypersomnia run parallel with the rise and fall of the
      causative diseases. Most of symptomatic hypersomnia cases show both extended
      nocturnal sleep time and EDS consisting of prolonged sleep episodes of NREM
      sleep. The features of nocturnal sleep and EDS in symptomatic hypersomnia are
      more similar to idiopathic hypersomnia than to narcolepsy.

PMID- 16986736
TI  - [Clinical and electroencephalographic analysis of epilepsy in children with
      hydrocephalus].
AB  - Clinical and electroencephalographic features of epilepsy and the prognosis of
      intelligence were investigated in 156 children with hydrocephalus. Of these 53
      (34.0%) had epilepsy. The incidence and outcome of epilepsy were determined by
      the etiology of hydrocephalus. The incidence was high in children with
      hydrocephalus caused by intra-cranial infection and dysgenetic hydrocephalus
      without dysraphism. Furthermore, it was difficult to control the epileptic
      seizures in these patients. In contrast, children with dysgenetic hydrocephalus
      caused by dysraphism and simple hydrocephalus had lower incidence of epilepsy and
      epileptic seizures had been well controlled in these cases. In hydrocephalic
      children, localization-related epilepsy was the most common. Complex partial
      seizures and focal motor seizures were frequently observed. Common
      electroencephalographic findings were focal spikes or multi-focal spikes. The
      intelligence quotient was significantly lower in children with epilepsy than in
      those without epilepsy. All these findings suggest that the incidence of epilepsy
      may be a crucial prognostic factor in children with hydrocephalus.

PMID- 16986737
TI  - [High-dose phenobarbital therapy is effective for the control of intractable
      tonic seizure with apnea in a case of multiple anomalies syndrome].
AB  - An 11-month-old boy with multiple surface anomalies and respiratory distress due
      to upper airway narrowing developed generalized tonic seizures coinciding with
      apnea. The ictal electroencephalography showed an abrupt onset of right-sided
      unilateral rapid activity with increasing amplitude followed by bursts of spike
      and wave complexes. The seizures were completely controlled with non-intravenous
      high-dose phenobarbital therapy. The serum level of phenobarbital at seizure
      control was 8 microg/ml. The serum level of phenobarbital peaked as high as 123
      microg/ml; the patient developed neither liver function abnormality nor
      hypotension which necessitated any pressor agents. Although the patient was
      intubated, spontaneous respiration was intact after seizure control. Extubation,
      however, failed twice because of diminished cough reflex. After decrease of the
      phenobarbital dose and the development of drug tolerance, the patient was
      successfully weaned from respiratory support. High-dose phenobarbital therapy is
      effective for refractory epilepsy in patients complicated by respiratory
      distress. Although it was reported that respiratory depression was not severe
      with high-dose phenobarbital therapy, respiratory status may worsen in such
      patients due to the diminished cough reflex. Therefore the careful and prolonged
      management is essential.

PMID- 16986738
TI  - [Two cases of acute disseminated encephalomyelitis which occurred before the age
      of 24 months].
AB  - We report two female cases of acute disseminated encephalomyelitis with onset of
      19 and 15 months, respectively. MRI demonstrated the T2-high lesions in the
      cerebral and cerebellar white matter, and the basal ganglia in addition to the
      spinal cord in the latter case. Treatment with high dose of intravenous
      methylprednisolone was effective to ameliorate the symptoms in both cases,
      although spasticity persists in the leg of the latter case. We review ten
      Japanese cases of acute disseminated encephalomyelitis with the onset before the
      age of 24 months, including our cases and eight reported cases in the
      literatures. And we found no significant interrelationships between age of onset
      and clinical features.

PMID- 16986739
TI  - [Case of 12-year-old boy with idiopathic recurrent neuralgic amyotrophy].
AB  - Here we report a 12-year-old boy with idiopathic neuralgic amyotrophy who had two
      episodes of shoulder pain followed by shoulder muscle atrophy and weakness at the
      age of 7 and 11 years, respectively. These symptoms were self-limited and
      disappeared within 9 months. During the second episode, electromyograph (EMG)
      revealed neurogenic changes in the deltoid muscle. Muscle imaging showed the
      right deltoid muscle atrophy with slightly high intensity areas on T1 and T2
      weighted images in MRI. Muscle biopsy from the right deltoid muscle revealed
      neurogenic changes with denervating and reinnervating processes. Neuralgic
      amyotrophy is characterized by neuralgic pain followed by weakness and atrophy at
      a unilateral extremity and is usually self-limited. EMG and imaging studies
      showed focal neurogenic abnormalities, which were confirmed by muscle biopsy.
      Neuralgic amyotrophy usually occurs in young adults and it is very rare in
      children.

PMID- 16986740
TI  - [Frontal N30 of median nerve short latency somatosensory evoked potentials and
      the brain image of basal ganglia in patients with athetotic cerebral palsy].

PMID- 16986741
TI  - [Driving license for persons with epilepsy--to drive or not to drive--].

PMID- 16986742
TI  - [Endoscopic ligation of maxillary and sphenopalatine artery for intractable
      epistaxis].
AB  - We report the endoscopic ligation of the maxillary and sphenopalatine arteries
      for the treatment of intractable epistaxis. From March 2003 to February 2005, 17
      patients (12 men, 5 women) with epistaxis were hospitalized in our department.
      Patient age ranged from 25 to 83 years, with an average age of 62 years. 8
      patients were successfully treated using the conventional packing method, 2
      patients were treated using electrocauterization, and 1 patient with
      macroglobulinemia was treated using plasma exchange therapy. 6 patients underwent
      endoscopic ligation of the maxillary and sphenopalatine arteries while under
      general anesthesia. The post operative courses were uneventful, and no recurrent
      bleeding has been noted. Endscopic ligation of the maxillary and sphenopalatine
      arteries is safer than intraarterial embolization and less invasive than
      conventional surgical approach for the ligation of maxillary artery. This
      technique appears to be a safe and effective surgical treatment for patients with
      intractable epistaxis.

PMID- 16986743
TI  - [Two cases of laryngoplasty performed under a general anesthesia applied using a
      laryngeal mask for the treatment of unilateral vocal cord paralysis].
AB  - In general, laryngoplasty for unilateral vocal cord paralysis is performed under
      local anesthesia because the patient's voice must be heard and the movement of
      the vocal cords visualized during the endoscopic procedure to ensure good
      results. We encountered two cases who could not endure a long operation under
      local anesthesia and the insertion of an endoscope because of their age and gag
      reflex. We thus performed a combined lateral cricoarytenoid muscle pull (LCA
      pull) and a type I thyroplasty under general anesthesia applied using a laryngeal
      mask. Although the patients could not phonate during the operation, the laryngeal
      mask allowed the vocal cords to be observed. Both patients achieved in maximal
      phonation time over 13 seconds, and the postoperative mean flow rates improved to
      under 110 mL/s. The postoperative period perturbation quotient and amplitude
      perturbation quotient also improved to within the normal limits.

PMID- 16986744
TI  - [Fluorogram using digital X-ray cineradiography].
AB  - We discussed the usefulness of fluorogram obtained using digital X-ray
      cineradiography (digital-cine-fluorograpy) in the diagnosis of dysphagia,
      comparied with that of video-fluorograpy. Digital-cine-fluorograpy produces five
      frames per second. A qualitative evaluation comfirmed that five frames per second
      was sufficient to grasp movement during swallowing in clinical setting. Digital
      cine-fluorograpy imaging was also convenient for clinical practice in that the
      medical records can be accessed from any workstation. Although the maximum
      photography time (around 10 seconds) is limited and a higher exposure dose is
      required, we concluded that digital-cine-fluorograpy is a useful tool for the
      diagnosis of dysphagia.

PMID- 16986747
TI  - Topical reaction.

PMID- 16986745
TI  - [Indications for pharyngeal surgery in adult with sleep-disordered breathing
      patients].
AB  - We assessed the indications for pharyngeal surgery, including tonsillectomy and
      uvulopalatopharyngoplasty (UPPP) for patients with sleep-disordered breathing
      (SDB). The indications for surgery can be divided into two groups. In the first
      group, the indicated surgery is a radical treatment of SDB. The characteristics
      of this group were (1) grade 1 tonsillar hypertrophy, (2) bilateral (side to side
      type) oropharyngeal stenosis, as determined using a snoring sound test, and (3)
      no risk of facial disfiguration. In this group, the improvement in AHI (Apnea
      Hypopnea Index) was 76.2%, while the improvement in AI (Apnea Index) was 95.7%.
      In the second group, the treatment was designated as supplemental. The
      characteristics of this group were (1) bilateral oropharyngeal stenosis, (2)
      tonsillar hypertrophy larger than grade 2, and (3) unsuccessful treatment with
      NCPAP (Nasal Continuous Positive Airway Pressure) or oral appliances. In this
      group, the improvement in AHI was 50.7%, but, surgery remained an effective means
      of treating SDB.

PMID- 16986748
TI  - Now and then: the first paediatrician.

PMID- 16986749
TI  - The use of blood products in paediatric oncology units in the UK.
AB  - AIM: The clinical practice group of the Royal College of Nursing paediatric
      oncology nurses' forum carried out an exploratory study to examine practice in
      administration of blood products in children's cancer centres across the UK to
      identify any variances in practice. METHOD: A questionnaire covering the use and
      administration of red cells, platelets and other supportive measures was
      distributed to each of the 22 UK Children's Cancer Study Groups centres of which
      14 responded (63 per cent). FINDINGS: Variations among the units were found in
      all aspects of blood product administration including decisions about when to
      transfuse, methods of transfusion, treatment of adverse reactions and use of
      supportive products. There were some differences between the practices reported
      and guidance for transfusion in neonates and older children published by the
      British Committee for Standards in Haematology Transfusion Task Force (2004);
      many of these differences were attributable to the specific needs of oncology
      patients. CONCLUSION: The development of national guidance or minimum safe
      standards specifically for paediatric oncology patients could assist in reducing
      practice variations. This study was undertaken in children's cancer units where
      administration of blood products is a daily occurrence. Variations in practice
      that were identified here are likely to be found in non oncology/haematology
      settings.

PMID- 16986750
TI  - Manual handling.

PMID- 16986751
TI  - Home-based palliative care for children: the case for funding.
AB  - Paediatric palliative care services have grown up in response to local needs with
      the result that provision is patchy and in some areas non-existent. Funding for
      existing services comes from a variety of sources and in the case of teams funded
      in 2003 from The New Opportunities Fund, there is uncertainty about future
      provision as funding streams come to an end. This article illustrates how home
      based palliative care achieves the objectives of the NHS Plan (DH 2000a) and
      makes the case for the continuation of paediatric palliative care teams already
      established through New Opportunities Fund (NOF) funding as these provide a ready
      made, quality service meeting the government agenda and addressing the needs of
      patients in a place and at a time to suit them.

PMID- 16986752
TI  - Too old at 18: a parent's view of transition.

PMID- 16986753
TI  - Growth assessment: how do we measure up?
AB  - Measurement of children's height and weight at regular intervals is important for
      identifying growth problems as well as for planning health promotion
      interventions for those at risk from under or over nutrition. Opportunistic
      measurement is recommended when children are seen by healthcare professionals for
      other reasons. Identification of variations in practice around measurement of
      height and weight in a children's unit led to the development of guidelines,
      purchase of new equipment, implementation of educational strategies and
      introduction of a growth link nurse role. Repeat audit revealed that these
      approaches did not bring about the desired changes in practice. Growth assessment
      is a quick, non invasive procedure that can provide valuable information about
      the general health and well being of the child but is perceived as a low priority
      by some healthcare professionals. Different approaches are needed to improve this
      important aspect of health care for children.

PMID- 16986754
TI  - Betterland: an interactive cd-rom guide for children with cystic fibrosis.
AB  - Effective management of cystic fibrosis (CF) depends on adherence to a daily
      multi-component regimen. Segregation policies have been reported to lead to a
      dramatic fall in the incidence of cross infection rates in specialist CF centres.
      Previously, peers provided a valuable source of information and support;
      segregation means that there is virtually no contact with other people with CF.
      In this context the Betterland CD-ROM was developed with the aim of improving
      knowledge and understanding and helping children and young people cope with time
      consuming CF treatments (inhalation therapies and physiotherapy) and painful
      procedures by using filmed-model approaches. Betterland is an interactive
      computer game, designed in the style of a theme park. Patient and carer feedback
      has been positive and the CD-ROM has been incorporated into a nurse-led Moving to
      High School (MotHS) programme, as well as the patient education work of the CF
      multidisciplinary team, particularly clinical nurse specialists.

PMID- 16986755
TI  - Genetics and paediatric nursing.
AB  - In response to major research initiatives in genetics, the government has
      invested significantly in new programmes of research and development for NHS
      staff (Department of Health (DH) 2003. Nurses may feel that these programmes have
      not yet impacted on their area of practice and are unlikely to for some time.
      Other priorities may be felt to be more important. This article considers the
      impact of genetics on the work of nurses who care for children and young people.
      It introduces a short questionnaire which we are using to identify and fill any
      gaps in knowledge, training and resources for nurses to prepare them to 'realise
      the potential of genetics' (DH 2003) in their practice.

PMID- 16986756
TI  - Short report: breaking news.

PMID- 16986757
TI  - The neonatal energy triangle. Part2: Thermoregulatory and respiratory adaption.
AB  - In the second part of this two part article the neonatal energy triangle elements
      of hypoxia and hypothermia are explored and the physiology of the first few hours
      of neonatal life drawn together into an integrated whole. This framework can
      assist in understanding the three most common difficulties encountered by the
      preterm baby and directing integrated and holistic care.

PMID- 16986758
TI  - Team building: a daily task.

PMID- 16986759
TI  - Managing your practice. AMS partners with athenahealth, Inc.

PMID- 16986760
TI  - Beginning in error.

PMID- 16986761
TI  - Preventing complications in diabetic patients: blood pressure control essential.

PMID- 16986762
TI  - On the drawing board. What's new in health care?

PMID- 16986763
TI  - Curing atrial fibrillation.

PMID- 16986764
TI  - Physicians play important role in families' long-term care decisions. Choice of
      home care vs. nursing home.
AB  - Physicians are often involved in decisions about long-term care for the elderly
      and adults with disabilities. In Arkansas, some home and community-based services
      (HCBS) have been established for these Medicaid-eligible populations, as a
      nursing home alternative, but some are under-utilized. Unnecessary use of nursing
      home care burdens the state Medicaid budget. A recent study on service
      utilization suggests that physicians' lack of knowledge about HCBS may be a
      factor in their under-utilization. A number of programs that enable individuals
      to remain in their homes in Arkansas, including ElderChoices, Alternatives, the
      Developmental Disabilities Waiver and the Assisted Living Waiver are described.

PMID- 16986765
TI  - Use of participatory epidemiology to compare the clinical veterinary knowledge of
      pastoralists and veterinarians in East Africa.
AB  - Because of severe resource and logistical constraints in large areas of Africa,
      disease surveillance systems need to maximize the use of information provided by
      livestock keepers and make correct interpretations of indigenous livestock
      knowledge. This paper describes the use of participatory epidemiology (PE) to
      compare the names, clinical signs and epidemiological features of cattle diseases
      as perceived by pastoralists and veterinarians. Using results from two previous
      studies with pastoralists in southern Sudan and Kenya, provisional translations
      of local disease names into modem veterinary terminology were used to develop a
      matrix scoring method for use with veterinarians. Matrix scoring data from
      pastoralists and veterinarians were then compared using simple visual comparison
      of summarized matrices, hierarchical cluster analysis and multidimensional
      scaling. The results showed good agreement between pastoralists' and
      veterinarians' disease names and diagnostic criteria. The matrix scoring method
      was easy to use and appropriate for use in under-resourced areas with minimal
      professional support or laboratory services. Matrix scoring could be used to
      assist livestock disease surveillance workers to design surveillance systems that
      make better use of pastoralist's indigenous knowledge and correctly interpret
      local disease names. The method should be combined with conventional veterinary
      investigation methods where feasible.

PMID- 16986766
TI  - Evaluation of the hygienic quality and associated public health hazards of raw
      milk marketed by smallholder dairy producers in the Dar es Salaam region,
      Tanzania.
AB  - A cross-sectional study was conducted to determine three parameters of the
      quality of the raw milk marketed by milk selling points (MSPs) in Dar es Salaam
      region. Total bacterial count (TBC) was used as an indicator of the microbial
      quality of the milk; antimicrobial residues were determined; and the California
      mastitis test (CMT) was used to screen for milk somatic cells as an indication of
      the mastitis level in the cows that provided the milk. Moreover, a water sample
      at each MSP was taken for bacteriological culturing. Finally, a questionnaire
      survey was conducted with the milk sellers at the MSPs to identify risk factors
      for poor milk hygiene. A total of 128 milk samples and corresponding water
      samples were collected from randomly selected milk selling points in Dar es
      Salaam region. The mean TBC was (8.2 +/- 1.9) x 10(6) cfu/ml, and major bacterial
      isolates from the milk samples were Escherichia coli (6.3%), Bacillus cereus
      (6.3%), Staphylococcus aureus (6.3%) and Streptococcus agalactiae (6.3%),
      Enterobacter aerogenes (5.6%) and Enterococcus faecalis (4.7%). In most cases,
      the organisms identified in milk corresponded to those isolated from the
      corresponding water samples. Of milk samples, 79.0% were positive to the CMT and
      7.0% were positive for antimicrobial residues. TBC was normalized by log
      transformation, and the possible predictors of TBC were identified by fitting two
      linear regression models. In a random effect model, water microbial quality,
      frequency of cleaning the milk containers, frequency of milk supply, milk storage
      time and the type of containers, and mixing of fresh and previous milk were
      significantly (p < 0.05) associated with the mean log TBC. In a fixed effect
      model, in addition to these indicators, water shortage, water source and the
      refrigerator condition were significantly (p < or = 0.01) associated with log
      TBC. It was concluded that the milk sold in Dar es Salaam region is of poor
      quality and is of public health significance.

PMID- 16986767
TI  - Prevalence of antibodies to Brucella spp. and individual risk factors of
      infection in traditional cattle, goats and sheep reared in livestock-wildlife
      interface areas of Zambia.
AB  - A cross-sectional study was performed in the livestock-wildlife interface areas
      of Lochinvar and Blue Lagoon National Parks and the non-interface area of
      Kazungula to determine the prevalence of antibodies to Brucella spp. in domestic
      ruminants and identify individual animal risk factors of infection. A total of
      1245 cattle from 124 herds and 280 goats and sheep from 29 flocks were tested
      sequentially for Brucella antibodies using the Rose Bengal test (RBT) and
      competitive ELISA. In cattle, individual seroprevalence ranged from 14.1% to
      28.1%, while herd sero-prevalence ranged from 46.2% to 74.0% in the three study
      areas. No goat or sheep tested positive for Brucella antibodies. Three types of
      cattle grazing strategies were encountered: locally grazed herds (LGH),
      transhumantly grazed herds (TGH) and river flood plain grazed herds (FGH).
      Brucella seroprevalence was seen to vary according to area and grazing strategy:
      Lochinvar and transhumant grazed herds recorded the highest figures,
      respectively. Age, sex and history of abortion were found to have independent
      effects on individual seroprevalence. This study establishes that brucellosis is
      endemic in domestic animals in the livestock-wildlife interface areas of Blue
      Lagoon and Lochinvar national parks and the disease is also present in Kazungula.
      We observed that type of grazing strategy had significant impact on cattle
      Brucella seroprevalence and that transhumant herds were at high risk of being
      infected.

PMID- 16986768
TI  - Camel tuberculosis--a case report.
AB  - An adult male dromedary bull was diagnosed with pulmonary tuberculosis (Tb). The
      dromedary was severely emaciated and died 2 months after the onset of the
      disease. It exhibited typical Tb lesions in both lungs and lung lymph nodes. A
      guinea pig inoculated with lung tissue from theTb camel died after 3 weeks from
      typical Tb. Mycobacteria were isolated from the dromedary's lung and lung lymph
      nodes and also from different organs of the guinea pig. The microorganism was
      identified as member of the antelope clade of the Mycobacterium tuberculosis
      complex.

PMID- 16986769
TI  - Assessment of anthelmintic resistance in nematode parasites of sheep and goats
      owned by smallholder farmers in eastern Ethiopia.
AB  - The anthelmintic resistance status was investigated of nematode parasites of
      sheep and goats owned by smallholder farmers in communities that received
      breeding stock from a source where a high level of anthelmintic resistance has
      been reported. The investigation used the faecal egg count reduction technique,
      whereby suitable animals within each of eight separate communities were pooled to
      achieve the numbers required to conduct separate tests for both sheep and goats.
      Anthelmintics tested were albendazole (ABZ), tetramisole (TET), a combination
      (ABZ + TET) and ivermectin (IVM), at the manufacturers' recommended dose rates.
      Results showed that there was no evidence of anthelmintic resistance in nematode
      parasites of either sheep an goats in any community. This indicates that dilution
      of resistant parasites imported with introduced breeding stock, and the low
      selection pressure imposed by the smallholder farmers themselves, has prevented
      anthelmintic resistance from emerging in nematode parasites of small ruminants in
      these communities.

PMID- 16986770
TI  - Free-range village chickens on the Accra Plains, Ghana: their contribution to
      households.
AB  - A cross-sectional survey investigating the contribution of free-range village
      chickens to household economies was carried out in four administrative districts
      within 60 km of Accra. Answers were provided by 101 men and 99 women. Nearly all
      respondents claimed to keep chickens for meat, with a far smaller percentage
      claiming to keep them for egg production. Over 80% of respondents kept chickens
      to supplement their incomes. The proportion of the flock eaten varied between
      administrative areas (p = 0.009 and p = 0.027), although this was possibly a
      consequence of differences in consumption patterns between occupation of the
      respondent, land area cultivated and flock size. The proportion of chickens sold
      varied as a result of differences in flock size (p = 0.013), the proportion sold
      increasing with number of birds in the flock. Respondents generally agreed that
      chickens could be sold without difficulty. A majority of chicken sales were from
      the farm gate, directly to consumers or traders. Sales were on demand or when the
      owner needed money. Money from the sale was kept by the owner of the chicken and
      the money was spent on personal needs. The proportion of the flock sold varied
      between administrative areas (p = 0.025) and occupation of the respondent (p =
      0.040). Respondents describing animal production as their main occupation tended
      to have greater reliance on chicken sales for their income. Consideration is
      given to estimating the offtake from the flock and the financial contribution to
      the household.

PMID- 16986771
TI  - Free-range village chickens on the Accra Plains, Ghana: their husbandry and
      productivity.
AB  - A cross-sectional[4pc] survey investigating husbandry and productivity of free
      range village chickens was carried out in four administrative districts within 60
      km of Accra. Responses were provided by 101 men and 99 women. The mean (SD)
      household flock size was 28.7 (25.97) and the median was 20. The factors included
      in the final model investigating variance in flock size were sex of the
      respondent (p = 0.011), administrative area (p = 0.004), the numbers of members
      in the household (p = 0.017) and the number of cattle, sheep and goats owned by
      the household (p = 0.031). Chickens were owned by individual members of the
      household, but women and children were the predominant providers of care for
      chickens. All respondents described their chickens as scavengers that were
      provided with supplementary feed, and over 80% of respondents named maize as a
      supplementary food source. Approximately 50% of respondents claimed difficulty in
      providing supplementary feed, with the degree of difficulty varying between
      administrative areas (p < 0.001). A majority of respondents (approximately 65%)
      claimed that their chickens laid 3-4 clutches of eggs per year. Over 70% of
      respondents estimated that each clutch contained 10-20 eggs, and approximately
      70% of respondents estimated that 75% of the eggs hatched. Opinions on mortality
      varied, but 60% of men and 70% of women estimated that between 50% and 75% of
      both chicks and adult birds died each year. Approximately 80% of respondents
      named Newcastle disease as the most important health issue. The opportunities for
      and consequences of controlling Newcastle disease are discussed.

PMID- 16986773
TI  - Milk production of West African Dwarf goats in the Gambia.
AB  - Goats are important in the low-input systems of West Africa and their main
      importance lies in their role for income and saving. In addition, it is known
      that milk offtake for home consumption is also important. In order to obtain
      information about the real importance of milk offtake, a recording scheme was
      operated in 27 villages in the Central River Division of The Gambia from July
      1998 until January 2000. Detailed information was obtained from about 1500
      kiddings. In the recording scheme, any sheep being milked as well as the goats of
      the International Trypanotolerance Centre nucleus flock were also recorded. In
      the villages, 36% of all lactations were used for milk offtake, but the fraction
      milked was lower for the first two lactations. The average length of lactation
      was 127 days and the average daily milk offtake was 0.18 L. Goats are milked once
      a day and the residual milk is left for the kids. Milking starts about one week
      after parturition and stops when the goat becomes pregnant or the kid(s) die or
      the goat is drying off. The repeatability of the 90-day milk offtake was 0.24 +/-
      0.09. Sixty-five percent of goat owner were women and a large fraction of goat
      owners also owned cattle. Goat milk was used exclusively for home consumption. It
      is concluded that in breeding and extension work more attention should be given
      to aspects of milk production.

PMID- 16986772
TI  - Gestational, periparturient and preweaning growth traits of Holstein versus Gir x
      Holstein F1 crossbred dairy calves born to Holstein dams.
AB  - The objectives of this study were to assess the gestational, periparturient and
      preweaning growth traits of Holstein vs Gir x Holstein (G x H F1) cross-bred
      dairy calves. Holstein cows (n=64) pregnant with Holstein (H x H) calves (bulls,
      n=16; heifers, n=18) or G x H (bulls, n=8; heifers, n=22) calves were sampled
      from 60 days of gestation through calving for serum progesterone (P4) and in
      utero placentome sizes, and at parturition for calving ease scores (CES), calf
      vigour scores (CVS), and placental characteristics. Post-calving calf measures
      included birth weight (day 0) and body weight (kg), hip width (HW), body length
      (BL), wither height (WH), hip height (HH) and heart girth (HG) through 42 days of
      age. Serum IgG and calf vital function tests (respiration rate (RR), heart rate
      (HR), rectal temperature (RT) and fecal scores) were recorded on days 1, 3, 7 and
      14 of age (a.m. and p.m.). Serum gestational P4 was higher (p < 0.05) for cows
      with H x H than G x H calves. Placentome measurements in utero were greater (p <
      0.01) for H x H calves than for G x H calves, while at parturition placental
      characteristics did not differ (p > 0.10). Gestation length, CES and CVS also did
      not differ (p > 0.10) between H x H and G x H calves. Calf RR and HR were higher
      (p < 0.05) for H x H than G x H calves at both a.m. and p.m., while RT, fecal
      scores and serum IgG did not differ (p > 0.10) between H x H and G x H calves.
      Birth weight did not differ (p > 0.10) between H x H and G x H calves within sex.
      Moreover, bulls did not differ (p > 0.10) in any of the growth measures between H
      x H and G x H calves, whereas H x H heifers at days 28 and 42 of age were greater
      (p < 0.05) in all growth traits than G x H heifers. Nevertheless, the relative
      change in growth measures over time (days 0 to 42) did not differ (p > 0.10)
      between H x H and G x H calves. While subtle differences in gestational, early
      growth and vital function characteristics were observed, these data suggest very
      similar developmental profiles between H x H and G x H calves.

PMID- 16986774
TI  - Time use and daily activities in people with persistent mental illness.
AB  - The aim of this study was to investigate time use in work/education, self
      care/self-maintenance, play/leisure, rest/relaxation, and sleep in people with
      persistent mental illness. A further aim was to investigate how time use in the
      daily activities was associated with health-related variables and social
      interaction. The study comprised 103 participants with a diagnosis of persistent
      mental illness who completed self-ratings and interviews in order to assess (1)
      time use of activities during one 24-hour day, (2) social interaction and (3)
      health-related factors. The major results indicated that the total time in
      activity (TTA) and the time spent on work/education and sleep seemed to be
      related to the majority of the target variables. Four groups of daily rhythm were
      identified and the daily rhythm groups differed concerning perceived mastery and
      social interaction. Although the results of this study were statistically
      significant they did not indicate clinical significance. Therefore, the
      assumption that there is a relationship between occupation and well-being could
      not be clearly verified. This study had a cross-sectional design based on a one
      time measure, which is an important limitation for the validity of the study.
      Furthermore, no Bonferroni corrections were made for mass significance and some
      of the findings would have disappeared if such corrections had been made. More
      studies concerning time use in daily activities, and daily rhythm in relation to
      health and well-being are needed.

PMID- 16986775
TI  - Promoting autonomy of the client with persistent mental illness: a challenge for
      occupational therapists from The Netherlands, Germany and Belgium.
AB  - The aim of this study was to determine how occupational therapists from The
      Netherlands, Germany and Belgium promote the autonomy of clients with persistent
      mental illness. Sixty occupational therapists working in psychosocial mental
      health completed two semi-structured questionnaires. Data were analysed by
      applying the constant comparative method. The results of the study show the
      importance of handling motivation in relation to personal autonomy and the
      different strategies occupational therapists use in promoting autonomy. In
      conclusion, enhancing clients' personal autonomy will empower and help them to
      discover meaningful occupations. More in-depth information could have been
      obtained using an interview in combination with observations. Further research is
      needed to evaluate the effectiveness of strategies used by occupational
      therapists in promoting clients' autonomy.

PMID- 16986776
TI  - The impact of time aids on independence and autonomy in adults with developmental
      disabilities.
AB  - The aim of this study was to describe how people with developmental disabilities
      experienced the use of time aids one year after their introduction by an
      occupational therapist. Data were obtained through semi-structured interviews.
      The analysis was performed using a phenomenographic qualitative approach. The
      results showed that independence and autonomy should be considered as two
      separate phenomena. Increased independence did not always lead to increased
      autonomy or vice versa. Four different relationships between these two phenomena
      were found. They all illustrate the different priorities of the participants and
      different levels of independence and autonomy. Concerning the usability of time
      aids, the occupational therapist has to recognize the importance of having
      frequent communication with the client to understand the phenomena that may
      affect the use of the aids. The occupational therapist should always try to
      involve both the client and significant support persons while introducing time
      aids. Future research in time aids with clients with developmental disabilities
      could involve multiple interviews with participants combined with participant
      observations and interviews.

PMID- 16986777
TI  - Cultural influences on occupational therapy practice in Singapore: a pilot study.
AB  - Over the past decades, numerous occupational therapy frameworks have been
      published and adopted in the West but there is little discussion of their
      applicability to Singapore. The purpose of this study was to examine the
      relevance and applicability of occupational therapy frameworks in Singapore. Data
      were gathered from nine highly experienced occupational therapists. Audio-taped
      semi-structured interviews were used to collect data. Qualitative methods were
      used in identifying five themes--independence, applicability of client-centred
      practice, concepts of occupation/activity, client's areas of concern, and
      application of occupational therapy models to practice. The themes were discussed
      in the context of three broad areas: (1) the potential discrepancy between
      occupational therapy's philosophical base and clients' values, (2) mismatch
      between the occupational therapists' prescription of activity and the meaning of
      activities to clients, and (3) the potential conflict between the occupational
      therapy approach and the corporate culture in Singapore. One of the important
      results from the study was that in Singapore culture, clients generally did not
      believe that achieving independence was important and they expected to be taken
      care of by their families. Further research with a larger sample is necessary to
      explore how culture and societal values impact on occupational therapy practice
      in Singapore.

PMID- 16986778
TI  - Field-based effects measures.

PMID- 16986779
TI  - In situ on-line toxicity biomonitoring in water: recent developments.
AB  - In situ on-line biomonitoring is an emerging branch of aquatic biomonitoring. On
      line biomonitoring systems use behavioral and/or physiological stress responses
      of caged test organisms exposed in situ either in a bypass system or directly in
      stream. Sudden pollution waves are detected by several existing single-species on
      line biomonitors, which until now have been placed mostly in streamside
      laboratories. However, recent achievements have been multispecies biomonitors,
      mobile biomonitors for direct in-stream use, development of new instruments, new
      methods for data analysis and alarm generation, biomonitors for use in soil and
      sediment, and scientific research supporting responses as seen in on-line
      biomonitors by linking them to other biological and ecological effects. Mobile on
      line monitoring platforms containing an array of biomonitors, biosensors, and
      chemical monitoring equipment might be the future trend, especially in monitoring
      transboundary rivers at country borders as well as in coastal zones.

PMID- 16986780
TI  - An in situ assay with the microalga Phaeodactylum tricornutum for sediment
      overlying water toxicity evaluations in estuaries.
AB  - Given the urgent need for ecologically relevant toxicity tools specific to
      estuarine systems, the main goal of the present study was to develop and evaluate
      the potential of an in situ algal assay for estuarine sediment-overlying water
      toxicity evaluations using the microalga Phaeodactylum tricornutum immobilized in
      alginate beads. With its simple and cost-effective design, the assay apparatus,
      coupled with the use of microalgae immobilized in alginate beads, allowed rapid
      and easy deployment as well as retrieval of assay chambers. The effectiveness of
      the proposed in situ assay was investigated by deploying it at two reference and
      six contaminated Portuguese estuaries. By deploying open chambers both with and
      without an artificial nutrient source and closed chambers with an artificial
      seawater medium, it was possible to discriminate toxic effects from those caused
      by differences in temperature, light, and nutrient conditions across sites. A
      reduction in algal growth was found at contaminated sites relative to reference
      sites. The strontium alginate beads used for microalgae immobilization were found
      to be appropriate to perform in situ assays, showing no signs of disruption or
      dissolution after up to 8 d of exposure in estuarine sediment-overlying waters.
      The proposed in situ assay was shown to be a useful tool for estuarine sediment
      overlying water toxicity testing to provide relevant data concerning primary
      production to estuarine ecological risk assessment studies.

PMID- 16986781
TI  - Effects of pulp and paper mill discharges on caged rainbow trout (Oncorhynchus
      mykiss): biomarker responses along a pollution gradient in the Biobio River,
      Chile.
AB  - Caging experiments were conducted using hatchery-reared, immature, female rainbow
      trout (Oncorhynchus mykiss) in three previously defined areas of the Biobio River
      (south central Chile) representing a pollution gradient from the pulp and paper
      mill discharges area: a pre-impact area (upstream area, reference location), an
      impact area (area directly influenced), and a postimpact area (downstream area,
      less influenced). No significant changes were observed in the physiological index
      as represented by condition factor (K) and liver somatic index during different
      sampling times (after 11, 21, and 30 d of exposure). Ethoxyresorufin-O-deethylase
      activities were significantly higher in trout caged at the impact and postimpact
      discharges areas (two- to fourfold) compared with the reference (pre-impact)
      area, and a strong inhibition of acetylcholinesterase activity, reaching 50%, was
      observed mainly in fish caged at the impact area. A significant endocrine
      disrupting effect (reproductive level) was evidenced by significant increments in
      gonad somatic index and plasma vitellogenin levels combined with an induction of
      gonad maturation (presence of vitellogenic oocytes) in trout caged at the impact
      and postimpact areas. These results, generated by an in situ approach, confirmed
      our group's findings for trout exposed to sediment in the laboratory: discharges
      of pulp mill effluent in the Biobio River are associated with the effects
      evaluated at different biological levels.

PMID- 16986782
TI  - Influence of water quality and associated contaminants on survival and growth of
      the endangered Cape Fear shiner (Notropis mekistocholas).
AB  - The Cape Fear shiner (Notropis mekistocholas) is a recently described cyprinid
      species endemic to the Cape Fear River Basin of North Carolina, USA. Only five
      populations of the fish remain; thus, it is listed as endangered by the U.S.
      Government. Determining habitat requirements of the Cape Fear shiner, including
      water quality and physical habitat, is critical to the survival and future
      restoration of the species. To assess water quality in the best remaining and in
      the historical habitats, we conducted a 28-d in situ bioassay with captively
      propagated Cape Fear shiners. Fish were deployed at 10 sites in three rivers,
      with three cages per site and 20 fish per cage. Water and sediment samples were
      collected and analyzed for selected metals and organic contaminants. Passive
      sampling devices also were deployed at each site and analyzed for organic
      contaminants at test termination. Fish survival, growth (as measured by an
      increase in total length), and contaminant accumulation were measured on
      completion of the bioassay. Survival of caged fish averaged 76% (range, 53-100%)
      and varied significantly among sites and rivers. Caged fish accumulated
      quantities of cadmium, mercury, polychlorinated biphenyls, and other persistent
      contaminants over the test duration and grew significantly at only four sites. No
      apparent relations were observed between exposure to or accumulation of a
      specific contaminant and reduced growth or survival of fish among all the sites.
      However, a generalized hazard assessment showed that certain sites exhibited
      trends in cumulative contaminant presence with reduced fish survival and growth,
      thereby enabling the identification of the existing riverine habitat most
      suitable for reintroduction or population augmentation of this endangered fish.

PMID- 16986783
TI  - Determining stressor presence in streams receiving urban and agricultural runoff:
      development of a benthic in situ toxicity identification evaluation method.
AB  - Determining toxicity in streams during storm-water runoff can be highly
      problematic because of the fluctuating exposures of a multitude of stressors and
      the difficulty of linking these dynamic exposures with biological effects. An
      underlying problem with assessing storm-water quality is determining if toxicity
      exists and then which contaminant is causing the toxicity. The goal of this
      research is to provide an alternative to standard toxicity testing methods by
      incorporating an in situ toxicity identification evaluation (TIE) approach. A
      benthic in situ TIE bioassay (BiTIE) was developed for separating key chemical
      classes of stressors in streams during both low- and high-flow events to help
      discern between point and nonpoint sources of pollution. This BiTIE method allows
      for chemical class fractionation through the use of resins, and these resins are
      relatively specific for removing nonpolar organics (Dowex Optipore), ammonia
      (zeolite), and polywool (control). Three indigenous aquatic insects, a mayfly
      (Isonychia spp.), a caddisfly (Hydropsyche spp.), and a water beetle (Psephenus
      herricki), were placed in BiTIE chambers that were filled with natural
      substrates. Acute 96-h exposures were conducted at Honey Creek, New Carlisle,
      Ohio, USA (reference site), and Little Beavercreek, Beavercreek, Ohio, USA
      (impaired site). At both sites, significant (p < 0.025) stressor responses were
      observed using multiple species with polywool or no resin (control) treatments
      exhibiting < 80% survival and resin treatments with >80% survival. The BiTIE
      method showed stressor-response relationships in both runoff and base flow events
      during 96-h exposures. The method appears useful for discerning stressors with
      indigenous species in situ.

PMID- 16986784
TI  - The use of in situ and stream microcosm experiments to assess population- and
      community-level responses to metals.
AB  - We conducted field and stream microcosm experiments to assess population-level
      (density, size distribution) and community-level (species richness metrics,
      multivariate analysis of community composition) responses of macroinvertebrates
      to heavy metals in the Arkansas River, a mining-polluted stream in Colorado, USA.
      Experiments were conducted in spring and summer to coincide with early and late
      developmental stages (i.e., instars) of the mayfly Rhithrogena hageni. Results of
      field experiments showed significant mortality at metal-contaminated sites during
      summer when mayfly populations were dominated by small, early instars (mean dry
      wt = 0.13 mg). In contrast, no significant mortality was observed in spring when
      organisms were larger (mean dry wt = 1.78 mg). Multivariate analyses based on
      abundance of dominant taxa clearly separated reference and metal-impacted
      stations in summer experiments but showed little separation in spring. We
      observed no significant effects of metals on species richness, number of mayfly
      species, or EPT (species richness of Ephemeroptera, Plecoptera, and Trichoptera)
      in.either field experiment. Using stream microcosms, we established concentration
      response relationships between heavy metals and R. hageni density, species
      richness, mayfly richness, and EPT. Density of R. hageni was generally more
      sensitive to metals than measures of species richness, and summer populations of
      R. hageni were more sensitive to metals than spring populations. Because the
      presence of large, relatively tolerant individuals in spring coincided with
      periods of higher metal concentrations, R. hageni was protected from toxic
      effects in this system. We conclude that phenology and developmental stage are
      important factors influencing responses of some aquatic macroinvertebrates to
      metals. Thus, timing bioassessments to coincide with the presence of these
      sensitive life stages can improve our ability to detect subtle contaminant
      effects.

PMID- 16986785
TI  - Quantum chemistry based quantitative structure-activity relationships for
      modeling the (sub)acute toxicity of substituted mononitrobenzenes in aquatic
      systems.
AB  - Fifteen experimental literature data sets on the acute toxicity of substituted
      nitrobenzenes to algae (Scenedesmus obliquus, Chlorella pyrenoidosa, C.
      vulgaris), daphnids (Daphnia magna, D. carinata), fish (Cyprinus carpio, Poecilia
      reticulata), protozoa (Tetrahymena pyriformis), bacteria (Phosphobacterium
      phosphoreum), and yeast (Saccharomyces cerevisiae) were used to establish quantum
      chemistry based quantitative structure-activity relationships (QSARs). The
      logarithm of the octanol/water partition coefficient, log Kow, and the energy of
      the lowest unoccupied molecular orbital, Elumo, were used as descriptors.
      Suitable QSAR models (0.65 < r2 < 0.98) to predict acute toxicity of substituted
      mononitrobenzenes to protozoa, fish, daphnids, yeast, and algae have been
      derived. The log Kow was a sufficient descriptor for all cases, with the
      additional Elumo descriptor being required only for algae. The QSARs were found
      to be valid for neutral substituted mononitrobenzenes with no -OH, -COOH, or -CN
      substituents attached directly to the ring. From the 100,196 European Inventory
      of Existing Commercial Substances (EINECS), 497 chemicals were identified that
      fit the selection criteria for the established QSARs. Based on these results, an
      advisory tool has been developed that directs users to the appropriate QSAR model
      to apply for various types of organisms within specified log Kow ranges. Using
      this tool, it is possible to obtain a good indication of the toxicity of a large
      set of EINECS chemicals and newly developed substituted mononitrobenzenes to five
      different organisms without the need for additional experimental testing.

PMID- 16986786
TI  - Identification of compounds associated with testosterone depressions in fish
      exposed to bleached kraft pulp and paper mill chemical recovery condensates.
AB  - In previous experiments, bleached kraft chemical recovery condensates generated
      during softwood pulp production have been identified as a primary source of
      substances causing testosterone depressions in mummichog (Fundulus heteroclitus).
      Recent toxicity identification evaluations have encountered inconsistencies in
      the potential of condensates and fractions to reduce steroid concentrations
      between three repeated exposures. To assess the sources of these inconsistencies,
      temporal assessments of condensate extractives and analytical methodologies were
      evaluated. Condensates were collected during a six-month period, extracted by
      solid-phase extraction (SPE), and analyzed by gas chromatography-mass
      spectrometry and gas chromatography-flame photometric detection. All unique
      extractives were cataloged by mass spectra, peak area, and gas chromatographic
      retention time, and nine were confirmed and quantified against authentic
      standards. Confirmed components included phenolic guaiacyl-based lignin
      degradation products, sulfur (S9), three diterpenoids, and a dimethoxy stilbene.
      Concentrations of confirmed condensate extractives were consistent in all samples
      collected. Spiking experiments of confirmed extractives revealed substantial
      losses following high-pressure liquid chromatographic fractionation and three
      different methods of fraction preparation. In an effort to propose chemical
      classes associated with biological activity, all unique condensate extractives in
      previously established bioactive and inactive fractions were classified based on
      their potential to depress testosterone in mummichog. Of 39 unique components in
      bioactive SPE extracts of condensates, six were associated with hormonal
      activity. Mass spectral interpretation indicated hydroxylated diterpenoids,
      sesquiterpenoids, and a lignin-derived stilbene as classes of chemicals
      associated with steroid depressions.

PMID- 16986787
TI  - Atmospheric dry deposition of trace metals in the coastal region of Los Angeles,
      California, U.S.A.
AB  - Emissions of trace metals to the atmosphere and subsequent deposition, either
      directly to a waterbody surface or indirectly to the watershed as washoff during
      rainfall, represents a potential source of contamination to surface waters near
      urban centers. The present study provides measurements of atmospheric
      concentrations of particle-bound trace metals, and it estimates the dry
      deposition mass loading of trace metals in coastal watersheds in the Los Angeles,
      California, USA, air basin. Coarse-particle atmospheric concentrations of metals
      were measured seasonally using a Noll Rotary Impactor at six urban sites and one
      nonurban site. Dry deposition fluxes were calculated by summing the product of
      air concentration and the theoretical deposition velocity for each particle size
      fraction. Mean fluxes at urban sites ranged from 3.2 to 9.1, 11 to 34, 3.8 to
      8.8, 8.3 to 29, and 69 to 228 microg/m2/d for chromium, copper, nickel, lead, and
      zinc, respectively. Mean concentrations and fluxes were significantly higher at
      urban sites compared with the nonurban site, although differences between urban
      and nonurban sites were reduced when sampling took place within 5 d after
      rainfall. Dry deposition to watershed land surfaces was substantial, representing
      a potentially large source of trace metals based on comparisons with load
      estimates from stormwater runoff.

PMID- 16986788
TI  - Leaching of copper, chromium, and boron from treated timber during aboveground
      exposure.
AB  - Field studies were conducted to evaluate leaching of Cu, Cr, and B from timber
      treated with a Cr, Cu, and B wood preservative and exposed aboveground in Spanish
      weathering conditions during one year with a total rainfall of approximately 500
      mm. The effect of timber orientation (horizontal for decks and vertical for
      fences) on metal leaching was assessed. Leaching of metals after one year was
      higher for decks than for fences, with total amounts of metals leached being
      226.6 and 87.8 mg/m2 for Cu, 199.5 and 42.4 mg/m2 for Cr, and 110.1 and 32.6
      mg/m2 for B from decks and fences, respectively. Leaching rates did not drop
      constantly with time, because an increase in metal leaching, except for B, was
      observed at the end of the year after a long dry period. The order of metal
      emission varied with cumulative rainfall: Leaching of B was higher than Cr
      initially, but the opposite occurred at the end of the assay. Total emissions of
      Cu and Cr obtained in a laboratory assay were lower than those for decks and
      fences under field conditions when expressed per unit surface area (mg/m2), but
      they were similar to the values obtained for fences when expressed as a
      percentage of the initial amount. However, the percentage of B leached from wood
      was higher in laboratory than in field assays for both orientations, with the
      amount of B leached per unit surface area under laboratory conditions being
      higher than that leached from fences but lower than that leached from decks.
      Emission rates extrapolated to one year from laboratory data underestimated metal
      leaching from decks and overestimated emissions from fences.

PMID- 16986789
TI  - Bioaccumulation of native polycyclic aromatic hydrocarbons from sediment by a
      polychaete and a gastropod: freely dissolved concentrations and activated carbon
      amendment.
AB  - The present paper describes a study on the bioaccumulation of native polycyclic
      aromatic hydrocarbons (PAHs) from three harbors in Norway using the polychaete
      Nereis diversicolor and the gastropod Hinia reticulata. First, biota-sediment
      accumulation factors (BSAFs) were measured in laboratory bioassays using the
      original sediments. Median BSAFs were 0.004 to 0.01 kg organic carbon/kg lipid
      (10 PAHs and 6 organism-sediment combinations), which was a factor of 89 to 240
      below the theoretical BSAF based on total sediment contents (which is
      approximately one). However, if BSAFs were calculated on the basis of measured
      freely dissolved PAH concentrations in the pore water (measured with
      polyoxymethylene passive samplers), it appeared that these BSAFfree values agreed
      well with the measured BSAFs, within a factor of 1.7 to 4.3 (median values for 10
      PAHs and six organism-sediment combinations). This means that for
      bioaccumulation, freely dissolved pore-water concentrations appear to be a much
      better measure than total sediment contents. Second, we tested the effect of 2%
      (of sediment dry wt) activated carbon (AC) amendments on BSAE The BSAFs were
      significantly reduced by a factor of six to seven for N. diversicolor in two
      sediments (i.e., two of six organism-sediment combinations), whereas no
      significant reduction was observed for H. reticulata. This implies that either
      site-specific evaluations of AC amendment are necessary, using several site
      relevant benthic organisms, or that the physiology of H. reticulata caused
      artifactually high BSAF values in the presence of AC.

PMID- 16986790
TI  - Seasonality effects on pharmaceuticals and s-triazine herbicides in wastewater
      effluent and surface water from the Canadian side of the upper Detroit River.
AB  - The influence of seasonal changes in water conditions and parameters on several
      major pharmacologically active compounds (PhACs) and s-triazine herbicides was
      assessed in the wastewater and sewage treatment plant (WSTP) effluent as well as
      the downstream surface water from sites on the Canadian side of the upper Detroit
      River, between the Little River WSTP and near the water intake of a major
      drinking water treatment facility for the City of Windsor (ON, Canada). The
      assessed PhACs were of neutral (carbamazepine, cotinine, caffeine,
      cyclophosphamide, fluoxetine, norfluoxetine, pentoxifylline, and trimethoprim)
      and acidic (ibuprofen, bezafibrate, clofibric acid, diclofenac, fenoprofen,
      gemfibrozil, indomethacin, naproxen, and ketoprofen) varieties. The major
      assessed s-triazine herbicides were atrazine, simazine, propazine, prometon,
      ametryn, prometryn, and terbutryn. At sampling times from September 2002 to June
      2003, 15 PhACs were detected in the WSTP effluent at concentrations ranging from
      1.7 to 1244 ng/L. The PhAC concentrations decreased by as much 92 to 100% at the
      Little River/Detroit River confluence because of the river dilution effect, with
      further continual decreases at sites downstream from the WSTP. The only
      quantifiable s-triazine in WSTP effluent, atrazine, ranged from 6.7 to 200 ng/L
      and was higher in Detroit River surface waters than in WSTP effluent. Only
      carbamazepine, cotinine, and atrazine were detectable at the low-nanogram and
      subnanogram levels in surface waters near a drinking water intake site. Unlike
      the PhACs, atrazine in the Detroit River is not attributable to point sources,
      and it is heavily influenced by seasonal agricultural usage and runoff. Detroit
      River surface water concentrations of carbamazepine, cotinine, and atrazine may
      present a health concern to aquatic wildlife and to humans via the consumption of
      drinking water.

PMID- 16986791
TI  - Characterization of Pb, Cu, and Cd adsorption on particulate organic matter in
      soil.
AB  - Evidence exists for significant metal enrichment in particulate organic matter
      (POM) compared to other soil constituents, but the relevant mechanisms are poorly
      understood. In the present study, adsorption of the heavy metals Pb, Cu, and Cd
      on a loamy soil and on POM separated from this soil was investigated. The
      adsorption kinetic data can be well described with a pseudo-second order model,
      whereas the equilibrium data are well fitted by a Langmuir model. Adsorption
      isotherms and kinetics data, in addition to the influence of pH on metal
      adsorption, showed that POM had a much higher adsorption capacity for Pb, Cu, and
      Cd compared to the whole soil. Ionic strength effects on metal adsorption,
      Fourier transform infrared spectroscopy, x-ray absorption spectroscopy x-ray
      absorption spectroscopy including x-ray absorption near-edge structure and
      extended x-ray absorption fine-structure spectroscopy were employed to elucidate
      the adsorption mechanisms. The results suggested that Pb and Cu adsorption on POM
      was mainly through inner-sphere complexes with carboxyl and hydroxyl groups.
      Cadmium was possibly adsorbed via outer-sphere complexation, indicated by the
      influence of ionic strength on Cd adsorption.

PMID- 16986792
TI  - Perfluorinated compounds in streams of the Shihwa Industrial Zone and Lake
      Shihwa, South Korea.
AB  - Concentrations of perfluorinated alkyl compounds (PFAs), including
      perfluorooctane sulfonate (PFOS), perfluorohexanesulfonate,
      perfluorobutanesulfonate, perfluorooctanesulfonamide, perfluorodecanoate,
      perfluorononanoic acid, perfluorooctanoate (PFOA), perfluoroheptanoate, and
      perfluorohexanoate, were measured in the streams of the Shihwa and Banweol
      industrial areas on the west coast of South Korea as well as the adjacent Lake
      Shihwa (an artificial lake) and Gyeonggi Bay. Perfluorinated alkyl compounds were
      concentrated from water using solid-phase extraction and were identified and
      quantified by liquid chromatography/ triple-quadrapole tandem mass spectrometry.
      Of the PFAs measured, PFOS and PFOA occurred at the greatest concentrations.
      Concentrations of PFOS ranged from 2.24 to 651 ng/L, and concentrations of PFOA
      ranged from 0.9 to 62 ng/L. The concentrations of PFOS observed in Lake Shihwa
      were among the greatest ever measured in the environment. These results suggest
      local industrial sources of PFOS and PFOA as well as other PFAs. Because of
      dilution, the greatest concentrations occur in a rather restricted area, near the
      points of discharge of the streams that empty into the lake. The greatest
      measured concentration of PFOS exceeded the threshold for effects predicted for
      predatory birds consuming aquatic organisms continuously exposed to this level.

PMID- 16986793
TI  - Effects of cyanobacterial toxins and cyanobacterial cell-free crude extract on
      germination of alfalfa (Medicago sativa) and induction of oxidative stress.
AB  - Cyanobacterial toxins have adverse effects on both terrestrial and aquatic
      plants. Microcystins are cyclic heptapeptides and an important group of
      cyanotoxins. When lake water contaminated with cyanobacterial blooms is used for
      spray irrigation, these toxins can come in contact with agricultural plants.
      During the exposure to these toxins, reactive oxygen species can form. These
      reactive oxygen species have a strong reactivity and are able to interact with
      other cellular compounds (lipids, protein, and DNA). Plants have antioxidative
      systems that will limit the negative effects caused by reactive oxygen species.
      These systems consist of enzymes, such as superoxide dismutase, catalase, and
      ascorbate peroxidase, and nonenzymatic substances, such as reduced glutathione or
      vitamins. The aim of the present study was to investigate the effects of
      cyanobacterial toxins (microcystins and anatoxin-a) and cyanobacterial cell-free
      crude extract on alfalfa (Medicago sativa) seedlings. Inhibition of germination
      and root growth was observed with toxin concentrations of 5.0 microg/L. Also,
      oxidative damage, such as lipid peroxidation, was detected after the exposure of
      alfalfa seedlings to the toxin. Reactive oxygen detoxifying enzymes were
      elevated, showing a marked response in alfalfa to oxidative stress caused by the
      exposure to cyanobacterial metabolites that might influence the growth and
      development of these plants negatively.

PMID- 16986794
TI  - Long-term exposure to environmentally relevant doses of methyl-tert-butyl ether
      causes significant reproductive dysfunction in the zebrafish (Danio rerio).
AB  - Methyl-tert-butyl ether (MTBE), an anthropogenic chemical used as a gasoline
      additive, is being detected at an increasing frequency in the environment. The
      acute lethal concentration that kills 50% of the fish test population and the
      chronic effects of exposure to MTBE were investigated in the zebrafish (Danio
      rerio). Chronic exposure over three weeks to effective MTBE conceritrations as
      low as 0.11 mg/L induced a significant increase in the vitellogenin concentration
      of male fish. The impact of a chronic, eight-week exposure at effective
      concentrations ranging from 0.44 to 220 mg/L had no significant effect on
      fecundity, fertilization, or hatch rate but highly significant impacts on sperm
      motility. Spermatozoa of all MTBE-exposure groups showed a significantly lower
      straight-line velocity and lower average path velocity compared to those of the
      nonexposed group. These results suggest that chronic exposure to MTBE negatively
      affects fish sperm motility at concentrations that are environmentally relevant
      and several orders of magnitude lower than concentrations inducing acute effects.

PMID- 16986795
TI  - Effects of dibutylphthalate and ethynylestradiol on liver peroxisomes,
      reproduction, and development of zebrafish (Danio rerio).
AB  - The aim of the present work was to study the effects of the peroxisome
      proliferator dibutylphthalate (DBP) and the xenoestrogen 17alpha-ethynylestradiol
      (EE2) on liver peroxisomes, reproduction, and development of zebrafish (Danio
      rerio). In experiment 1, newly fertilized zebrafish eggs were exposed for five
      weeks, covering the entire period of sexual determination, to nominal
      concentrations of 25 and 100 microg/L of DBP and 5 microg/L of EE2. In experiment
      2, adult female zebrafish were exposed for 15 d to 100 and 500 microg/L of DBP
      and 5 microg/L of EE2, and afterward, they were paired with untreated males to
      study the effects in the resultant offspring. Ethynylestradiol provoked marked
      mortality (approximately 50%) and delayed development of larvae as well as
      sterility of adult females, possibly related to alterations in aromatase gene
      expression. Ethynylestradiol up-regulated vitellogenin expression in the early
      life stages and increased vitellogenin synthesis and accumulation in adult
      females. Ethynylestradiol caused liver peroxisome proliferation in early life
      stages but not in adult females. Dibutylphthalate caused teratogenic effects in
      early life stages and mortality of the larvae obtained from exposed females.
      Dibutylphthalate provoked liver peroxisome proliferation and up-regulation of
      cytochrome P450A1 in early life stages at the end of the exposure and in adult
      females. Dibutylphthalate also up-regulated the expression of aromatase genes. In
      conclusion, the xenoestrogen EE2 caused liver peroxisome proliferation in early
      life stages of zebrafish, but the peroxisome proliferator DBP did not behave as a
      typical xenoestrogen. Overall, changes in gene expression were more marked during
      early life stages than in adult female zebrafish.

PMID- 16986796
TI  - Perfluoroalkyl compounds in relation to life-history and reproductive parameters
      in bottlenose dolphins (Tursiops truncatus) from Sarasota Bay, Florida, U.S.A.
AB  - Perfluoroalkyl compounds (PFCs) were determined in plasma, milk, and urine of
      free-ranging bottlenose dolphins (Tursiops truncatus) from Sarasota Bay (FL, USA)
      during three winter and two summer capture-and-release programs (2002-2005).
      Plasma and urine samples were extracted using an ion-pairing method.
      Perfluoroalkyl compounds were extracted from milk samples using acetonitrile, and
      extracts were cleaned with graphitized nonporous carbon. All extracts were
      analyzed by high-performance liquid chromatography-tandem mass spectrometry. Mean
      seasonal sum of PFCs (sigma PFCs) detected in dolphin plasma ranged from 530 to
      927 ng/g wet weight. No significant differences (p > 0.05) were found in
      concentrations between seasons, suggesting a constant exposure to PFCs. Overall,
      blubber thickness of dolphins did not correlate with PFC concentrations in
      plasma, suggesting an absence of PFC sequestration in blubber. Sexually immature
      calves (age, <10 years; mean sigma PFCs, 1,410 +/- 780 ng/ g wet wt) were
      significantly more contaminated (p < 0.001) than their mothers (mean sigma PFCs,
      366 +/- 351 ng/g wet wt). The reproductive history of females had a significant
      role in the burden of PFC contamination; PFC concentrations in nulliparous
      females (females that have not been observed with calves) were significantly
      greater than those detected in uniparous females (females that have been observed
      with one calf), suggesting an off-loading of PFCs during or after parturition. To
      investigate this hypothesis, PFCs were analyzed in milk samples (n=10; mean sigma
      PFCs, 134 +/- 76.1 ng/g wet wt), confirming a maternal transfer of PFCs through
      lactation in dolphins. Results from the present study showed that young and
      developing bottlenose dolphins are highly exposed to PFCs. These chemicals also
      were detected in urine (mean sigma PFCs, 26.6 +/- 79 ng/g wet wt), indicating
      that the urinary system is an important pathway of PFC depuration in dolphins.

PMID- 16986797
TI  - Estrogenicity patterns in the Swiss midland river Lutzelmurg in relation to
      treated domestic sewage effluent discharges and hydrology.
AB  - Sewage treatment works (STW) discharge estrogenic effluent into rivers, which
      leads to variable estrogenicity of river water. Here, we characterize how the
      factors effluent and hydrology influence the estrogenicity of river water. We
      selected a river for which good hydrological data are available and collected
      water samples upstream and downstream from a STW discharge; effluent was sampled
      as well. Sampling took place during four 12-d periods, associated with the
      seasons, and always occurred in the morning. We also investigated the
      estrogenicity along the river, both by grab sampling and by passive sampling.
      Estrogens were analyzed by a recombinant yeast assay (YES); the estrogenicity of
      a sample was equated to the 17beta-estradiol standard of the YES (ng/L).
      Estrogenicity upstream from the STW was mostly close to the detection limit of
      the YES (maximum, 0.4 ng/L). Estrogenicity of effluent ranged between 0.2 and 7.7
      ng/L; lower estrogenicity was associated with higher hydraulic retention times.
      Downstream from the STW, estrogenicity exceeded 1 ng/L on 25% of the days
      (maximum, 2.1 ng/L). Measured river water estrogenicity correlated positively and
      significantly with predicted estrogenicity based on effluent estrogenicity and
      effluent dilution factor. Grab samples taken along the river indicate that no
      significant sources of estrogens were upstream from the STW; downstream from the
      STW, the pattern of estrogenicity was highly variable. However, passive sampling
      showed that the estrogenicity of river water downstream from the STW decreased
      continuously with increasing distance from the STW, which is largely explained by
      dilution.

PMID- 16986798
TI  - Chronic toxicity of polycyclic aromatic compounds to the springtail Folsomia
      candida and the enchytraeid Enchytraeus crypticus.
AB  - An urgent need exists for incorporating heterocyclic compounds and
      (bio)transformation products in ecotoxicological test schemes and risk assessment
      of polycyclic aromatic compounds (PACs). The aim of the present study therefore
      was to determine the chronic effects of (heterocyclic) PACs on two terrestrial
      invertebrates, the springtail Folsomia candida and the enchytraeid Enchytraeus
      crypticus. The effects of 11 PACs were determined in chronic experiments using
      reproduction and survival as endpoints. The results demonstrated that as far as
      narcosis-induced mortality is concerned, effects of both homocyclic and
      heterocyclic PACs are well described by the relationship between estimated pore
      water 50% lethal concentrations and log Kow. In contrast, specific effects on
      reproduction varied between species and between compounds as closely related as
      isomers, showing up as deviations from the relationship between pore-water 50%
      effect concentrations and log Kow. These unpredictable specific effects on
      reproduction force one to test the toxicity of these PACs to populations of soil
      invertebrates to obtain reliable effect concentrations for use in risk assessment
      of PACs.

PMID- 16986799
TI  - Geckos as indicators of mining pollution.
AB  - Catastrophic collapse of a mine tailings dam released several million cubic
      meters of toxic mud and acidic water into the Guadiamar River valley, southern
      Spain, in 1998. Remediation efforts removed most of the sludge from the
      floodplain, but contamination persists. Clean-up activities also produced clouds
      of aerosolized materials that further contaminated the surrounding landscape.
      Whole-body concentrations of 21 elements in the Moorish wall gecko, Tarentola
      mauritanica, a common inhabitant of both rural and urban areas, were compared
      among seven locations. Locations spanned an expected contamination gradient and
      included a rural and an urban non-mine-affected location, two mine-affected
      towns, and three locations on the contaminated floodplain. Multivariate analyses
      of whole-body concentrations identified pollutants that increased across the
      expected contamination gradient, a trend particularly evident for As, Pb, and Cd.
      Additionally, higher contaminant concentrations occurred in prey items eaten by
      geckos from mine-affected areas. Comparison of element concentrations in tails
      and whole bodies suggests that tail clips are a viable nondestructive index of
      contaminant accumulation. Our results indicate that areas polluted by the mine
      continue to experience contamination of the terrestrial food chain. Where
      abundant, geckos represent useful taxa to study the bioavailability of some
      hazardous pollutants.

PMID- 16986800
TI  - Cholinesterase activity and behavior in chlorpyrifos-exposed Rana sphenocephala
      tadpoles.
AB  - Recent studies have found a correlation between organophosphate (OP) pesticide
      exposure and declines in amphibian populations. We evaluated the hypothesis that
      this relationship is driven by behavioral changes in developing larvae.
      Specifically, we examined how exposure to a common OP pesticide, chlorpyrifos,
      influenced cholinesterase (ChE) activity, mass, and swim speed in Rana
      sphenocephala tadpoles. We also determined how the presence of natural pond
      sediments in exposure chambers influenced response to the pesticide and how mass
      and survival were affected when tadpoles were exposed to an invertebrate
      (odonate) predator in addition to the pesticide. Mass and swim speed were
      measured after 4- and 12-d laboratory exposures to 1, 10, 100, and 200 microg/L
      of chlorpyrifos in test chambers that either did or did not contain pond
      sediments. These same parameters also were examined in mesocosms dosed with 200
      microg/L of chlorpyrifos to evaluate responses under more environmentally
      realistic conditions. The effect of the invertebrate predators on survival and/or
      growth of tadpoles was evaluated in the mesocosm study and in separate laboratory
      experiments. In laboratory tests, no pesticide-induced mortality was observed;
      however, tadpole ChE activity in the two highest concentrations was significantly
      lowered, with a longer exposure duration further decreasing activity (maximum
      inhibition, 43%). Mass also was lower at higher concentrations, but this effect
      was not enhanced with longer duration of exposure. Reductions in ChE activity of
      tadpoles exposed in mesocosms were similar to those observed in laboratory
      experiments for the first 4 d. Tadpole swim speed and survival in the presence of
      a predator were not affected, with the latter largely resulting from pesticide
      induced predator mortality.

PMID- 16986801
TI  - Uptake, removal, accumulation, and phytotoxicity of phenol in willow trees (Salix
      viminalis).
AB  - Phenol is an intermediate in the metabolism of plants, but it also is a high
      volume production compound frequently found in the environment. The relation
      between removal, uptake, accumulation, and toxicity of phenol in willow trees
      (Salix viminalis) was determined. Willows were exposed to phenol levels up to
      1000 mg/L in hydroponic solution and sand, respectively. The change on water
      transpiration of the trees was used to determine toxic effects. In both
      hydroponic solution and sand, only small inhibition of transpiration was detected
      up to phenol concentrations of 250 mg/L. For concentrations of 500 mg/L or
      greater, transpiration fell to 50% or less, and the trees wilted. The trees
      exposed to 1000 mg/L wilted and eventually died. For initial nominal
      concentrations of 1000 mg/L, a significantly higher amount of phenol remained at
      the end of the experiment compared to the amount remaining with all other
      concentrations. Phenol loss was approximately 90% for the trees that survived,
      except for trees exposed to the lowest concentration (10 mg/L). The loss of
      phenol was only 15 to 18% in experiments performed without trees. The results
      demonstrate a clear relation between removal, accumulation, and toxic effects of
      phenol in trees. Phenol levels of less than 250 mg/L could be degraded by "in
      planta" metabolism; therefore, no significant buildup of phenol nor any toxic
      effects in plants occurred. With higher levels, phenol was still degraded
      quickly, but an accumulation in trees accompanied by severe toxic effects
      occurred. Phytoremediation of phenol would be best with concentrations in water
      or soil solution of less than 250 mg/L, at which the degradation of phenol by
      willows or associated bacteria is rapid and efficient and the toxic effects on
      trees are negligible.

PMID- 16986802
TI  - Combined effects of temperature acclimation and cadmium exposure on mitochondrial
      function in eastern oysters Crassostrea virginica gmelin (Bivalvia: Ostreidae).
AB  - Cadmium and temperature have strong impacts on the metabolic physiology of
      aquatic organisms. To analyze the combined impact of these two stressors on
      aerobic capacity, effects of Cd exposure (50 microg/L) on mitochondrial function
      were studied in oysters (Crassostrea virginica) acclimated to 12 and 20 degrees C
      in winter and to 20 and 28 degrees C in fall. Cadmium exposure had different
      effects on mitochondrial bioenergetics of oysters depending on the acclimation
      temperature. In oysters acclimated to 12 degrees C, Cd exposure resulted in
      elevated intrinsic rates of mitochondrial oxidation, whereas at 28 degrees C, a
      rapid and pronounced decrease of mitochondrial oxidative capacity was found in Cd
      exposed oysters. At the intermediate acclimation temperature (20 degrees C),
      effects of Cd exposure on intrinsic rates of mitochondrial oxidation were
      negligible. Degree of coupling significantly decreased in mitochondria from 28
      degrees C-acclimated oysters but not in that from 12 degrees C- or 20 degrees C
      acclimated oysters. Acclimation at elevated temperatures also increased
      sensitivity of oyster mitochondria to extramitochondrial Cd. Variation in
      mitochondrial membrane potential explained 41% of the observed variation in
      mitochondrial adenosine triphosphate synthesis and proton leak between different
      acclimation groups of oysters. Temperature-dependent sensitivity of metabolic
      physiology to Cd has significant implications for toxicity testing and for
      extrapolation of laboratory studies to field populations of aquatic
      poikilotherms, indicating the importance of taking into account the thermal
      regime of the environment.

PMID- 16986803
TI  - Ecological consequences of copper contamination in macroalgae: effects on
      epifauna and associated herbivores.
AB  - Many contaminants of the marine environment are able to chelate to sediments,
      bind within organic matrices, or be accumulated by organisms such as
      invertebrates and macroalgae. Marine macroalgae are recognized as effective and
      efficient bioaccumulators of heavy metals and are sometimes used as
      bioindicators. Macroalgae support abundant and diverse communities of mobile
      invertebrates that play key roles in temperate marine environments. However, the
      potential ecological consequences of the contamination of algae on associated
      epifauna are yet to be considered. In this study, the brown alga Sargassum
      linearifolium was experimentally spiked with copper to assess the effects of
      contamination on epifaunal invertebrates in both field and laboratory assays.
      Copper contamination greatly reduced the colonization of a variety of epifaunal
      taxa in the field. Laboratory assays further examined the effects of contaminated
      macroalgae on habitat preferences, feeding rates, survivorship, and growth in the
      herbivorous amphipod Peramphithoe parmerong. Adult P. parmerong were less likely
      to select spiked macroalgae in short-term habitat preference assays and consumed
      spiked algae at lower rates in feeding assays. In a longer-term (30-d)
      experiment, survivorship of juvenile amphipods was reduced by up to 75% by
      contaminated macroalgae, but no effects on the growth of survivors was observed.
      Heavy metal contamination of macroalgae is a widespread phenomenon that has the
      potential for substantial negative consequences for associated invertebrate
      fauna. This issue warrants further investigation by marine ecotoxicologists.

PMID- 16986804
TI  - Effects of pesticides on soil invertebrates in laboratory studies: a review and
      analysis using species sensitivity distributions.
AB  - Species sensitivity distributions (SSD) and 5% hazardous concentrations (HC5) are
      distribution-based approaches for assessing environmental risks of pollutants.
      These methods have potential for application in pesticide risk assessments, but
      their applicability for assessing pesticide risks to soil invertebrate
      communities has not been evaluated. Using data obtained in a systematic review,
      the present study investigates the relevance of SSD and HC5 for predicting
      pesticide risks to soil invertebrates. Altogether, 1950 laboratory toxicity data
      were obtained, representing 250 pesticides and 67 invertebrate taxa. The majority
      (96%) of pesticides have toxicity data for fewer than five species. Based on a
      minimum of five species, the best available endpoint data (acute mortality median
      lethal concentration) enabled SSD and HC5 to be calculated for 11 pesticides
      (atrazine, carbendazim, chlorpyrifos, copper compounds, diazinon, dimethoate,
      gamma-hexachlorocyclohexane, lambda-cyhalothrin, parathion, pentachlorophenol,
      and propoxur). Arthropods and oligochaetes exhibit pronounced differences in
      their sensitivity to most of these pesticides. The standard test earthworm
      species, Eisenia fetida sensu lato, is the species that is least sensitive to
      insecticides based on acute mortality, whereas the standard Collembola test
      species, Folsomia candida, is among the most sensitive species for a broad range
      of toxic modes of action (biocide, fungicide, herbicide, and insecticide). These
      findings suggest that soil arthropods should be tested routinely in regulatory
      risk assessments. In addition, the data indicate that the uncertainty factor for
      earthworm acute mortality tests (i.e., 10) does not fully cover the range of
      earthworm species sensitivities and that acute mortality tests would not provide
      the most sensitive risk estimate for earthworms in the majority (95%) of cases.

PMID- 16986805
TI  - Effects of pesticides on soil invertebrates in model ecosystem and field studies:
      a review and comparison with laboratory toxicity data.
AB  - A systematic review was carried out to investigate the extent to which higher
      tier (terrestrial model ecosystem [TME] and field) data regarding pesticide
      effects can be compared with laboratory toxicity data for soil invertebrates.
      Data in the public domain yielded 970 toxicity endpoint data sets, representing
      71 pesticides and 42 soil invertebrate species or groups. For most pesticides,
      the most frequent effect class was for no observed effects, although relatively
      high numbers of pronounced and persistent effects occurred when Lumbricidae and
      Enchytraeidae were exposed to fungicides and when Lumbricidae, Collembola, and
      Arachnida were exposed to insecticides. No effects of fungicides on Arachnida,
      Formicidae, or Nematoda or of herbicides on Lumbricidae, Formicidae, or Nematoda
      were observed in any studies. For most pesticides, higher-tier no-observed-effect
      concentration or lowest-observed-effect concentration values cannot be determined
      because of a lack of information at low pesticide concentrations. Ten pesticides
      had sufficient laboratory data to enable the observed higher-tier effects to be
      compared with 5% hazardous concentrations (HC5) estimated from acute toxicity
      laboratory data (atrazine, carbendazim, chlorpyrifos, diazinon, dimethoate, gamma
      hexachlorocy-clohexane, lambda-cyhalothrin, parathion, pentachlorophenol, and
      propoxur). In eight cases, higher-tier effects concentrations were within or
      below the 90% confidence interval of the HC5. Good agreement exists between the
      results of TME and field tests for carbendazim, but insufficient information is
      available for a comparison between TME and field studies for other pesticides.
      Availability and characteristics (e.g., taxonomic composition and heterogeneity)
      of the higher-tier effects data are discussed in terms of possible developments
      in risk assessment procedures.

PMID- 16986806
TI  - Biomagnification of polybrominated diphenyl ether and hexabromocyclododecane
      flame retardants in the polar bear food chain in Svalbard, Norway.
AB  - Concentrations of brominated flame retardants (BFRs), including polybrominated
      diphenylethers (PBDEs) and hexabromocyclododecane (HBCD), were investigated in an
      arctic marine food chain consisting of four invertebrate species: polar cod
      (Boreogadus saida), ringed seals (Pusa hispida), and polar bears (Ursus
      maritimus). The most abundant BFR, brominated diphenyl ether (BDE)-47, was found
      in detectable concentrations even in zooplankton, the lowest trophic level
      examined in this study. Most of the investigated BFRs biomagnified as function of
      tropic level in the food chain. A noticeable exception occurred at the highest
      trophic level, the polar bear, in which only BDE-153 was found to increase from
      its main prey, the ringed seal, indicating that polar bears appear to be able to
      metabolize and biodegrade most BFRs. In contrast, lower-brominated PBDEs,
      particularly BDE-47, showed clear signs of bioaccumulation in zooplankton, polar
      cod, and ringed seals. We suggest that this discrepancy in the fate of BFRs among
      the different species may be related to greater induction of oxidative
      detoxification activities in the polar bear. Absorption and debromination rates
      may be more important for bioaccumulation rates of BFRs in zooplankton, polar
      cod, and ringed seals. Lipid weight-based concentrations (LWCs) and whole body
      based concentrations (WBCs) of BFRs were used to assess biomagnification factors
      (BMFs). Whole-body concentrations gave the most realistic BMFs, as BMFs derived
      from LWCs seem to be confounded by the large variability in lipid content of
      tissues from the investigated species. This study demonstrates that PBDEs and
      HBCD have reached measurable concentrations even in the lower trophic levels
      (invertebrates and fish) in the Arctic and biomagnifies in the polar bear food
      chain.

PMID- 16986807
TI  - Chlorine toxicity to early life stages of freshwater mussels (Bivalvia:
      Unionidae).
AB  - Chlorine (Cl) is a highly toxic, widely used halogen disinfectant that is present
      in point-source pollution discharges from wastewater treatment plants and
      industrial facilities. The U.S. Environmental Protection Agency freshwater
      criteria for Cl are 19 microg total residual Cl (TRC)/L as a maximum 1-h average
      concentration and 11 microg TRC/L as a maximum 4-d average; however,
      toxicological data for unionids were not used in these calculations. To address
      this void in the data, we conducted acute tests with glochidia from several
      species and 21-d bioassays with three-month-old Epioblasma capsaeformis and three
      , six-, and 12-month-old Villosa iris juveniles. The 24-h lethal concentration 50
      values for glochidia were between 70 and 220 [Lg TRC/L, which are 2.5 to 37 times
      higher than those reported in other studies for cladocerans. Significant declines
      in growth and survivorship were observed in the 21-d test with E. capsaeformis at
      20 microg TRC/L. Lowest-observed-adverse-effects concentrations in bioassays with
      juvenile V. iris were higher (30-60 microg TRC/L) but showed a significant trend
      of declining toxicity with increased age. Although endpoints were above water
      quality criteria, the long life spans of unionids and potential implications of
      chronic exposure to endangered juvenile mussels still warrant concern.

PMID- 16986808
TI  - Transgenerational retention and maternal transfer of selenium in Daphnia magna.
AB  - We examined transgenerational retention and maternal transfer of selenium (Se) in
      three consecutive generations (F0, F1, and F2) of Daphnia magna. The F0
      generation was exposed to dietary selenium (as selenite) only, and the F1 and F2
      generations received only the maternally derived selenium from F0 and F1,
      respectively. Algal food Scenedesmus obilquus was radiolabeled with 0.56 microM
      Se, and the finial Se concentration in the algae was 115.6 microg Se/g dry
      weight. After 10 d feeding, the initial Se concentration in the F0 prior to
      depuration was 0.72 microg Se/g wet weight. The Se retention within the same
      generation was comparable at different food concentrations, but it increased
      across the consecutive generations regardless of the food concentration,
      suggesting that Se elimination was dependent on the source of Se accumulation
      (dietary vs maternally derived). Retention was also comparable among different
      batches of offspring within the same generation. Reproduction rate increased with
      increasing food concentration but decreased across the successive batches in F1.
      The 10-d overall maternal transfer efficiency increased with increasing food
      concentration in all generations. Approximately 19 to 24% of Se in F0 was
      transferred maternally to F1 during reproductive events, but the-efficiency
      decreased considerably from F1 to F2. Maternal transfer also decreased in the
      later batches of F1. The transfer efficiency to each neonate showed a negative
      relationship with food concentration in both F0 and F1, suggesting that the Se
      transfer to the offspring was compromised by the reproduction rate. We concluded
      that dietary-derived Se (from F0) was more efficiently transferred to the
      offspring (F1) than the maternally derived Se (from F1) transferred to F2; thus
      it is necessary to separate the dietary and maternal contributions to the overall
      Se accumulation in Daphnia.

PMID- 16986810
TI  - Evaluation of statistical methods for left-censored environmental data with
      nonuniform detection limits.
AB  - Monte Carlo simulations were used to evaluate statistical methods for estimating
      95% upper confidence limits of mean constituent concentrations for left-censored
      data with nonuniform detection limits. Two primary scenarios were evaluated: data
      sets with 15 to 50% nondetected samples and data sets with 51 to 80% nondetected
      samples. Sample size and the percentage of nondetected samples were allowed to
      vary randomly to generate a variety of left-censored data sets. All statistical
      methods were evaluated for efficacy by comparing the 95% upper confidence limits
      for the left-censored data with the 95% upper confidence limits for the
      noncensored data and by determining percent coverage of the true mean (micro).
      For data sets with 15 to 50% nondetected samples, the trimmed mean,
      Winsorization, Aitchison's, and log-probit regression methods were evaluated. The
      log-probit regression was the only method that yielded sufficient coverage (99
      100%) of micro, as well as a high correlation coefficient (r2 = 0.99) and small
      average percent residuals (-0.1%) between upper confidence limits for censored
      versus noncensored data sets. For data sets with 51 to 80% nondetected samples, a
      bounding method was effective (r2 = 0.96 - 0.99, average residual = -5% to -7%,
      95-98% coverage of micro), except when applied to distributions with low
      coefficients of variation (standard deviation/micro < 0.5). Thus, the following
      recommendations are supported by this research: data sets with 15 to 50%
      nondetected samples--log-probit regression method and use of Chebyshev theorem to
      estimate 95% upper confidence limits; data sets with 51 to 80% nondetected
      samples-bounding method and use of Chebyshev theorem to estimate 95% upper
      confidence limits.

PMID- 16986809
TI  - Toxicity of a cadmium-contaminated diet to Hyalella azteca.
AB  - Four- and 10-week chronic toxicity tests were conducted using the freshwater
      amphipod Hyalella azteca and Cd-contaminated Chlorella sp. as a food source.
      Chlorella sp. was cultured in various Cd concentrations, filtered from solution,
      rinsed, dried, and ground into food flakes for the H. azteca. Unlike Cd toxicity
      from water sources, growth was found to be a more sensitive toxicological
      endpoint than survival, with calculated 50 and 25% effect concentrations (EC50s
      and EC25s, respectively) of 5.43 and 2.82 nmol/g, respectively, for Cd measured
      in food. Based on the regression of Cd in Chlorella sp. against Cd in filtered
      culture medium, the EC50 and EC25 corresponded to dissolved Cd concentrations of
      11.30 and 5.09 nmol/L, respectively. Little or no bioaccumulation of Cd was found
      in the tissues of H. azteca that were fed contaminated food. These results
      demonstrate an apparent toxicological effect (either direct or indirect) of Cd
      contaminated Chlorella sp. to H. azteca that is not associated with Cd
      accumulation. Toxicity of Cd-contaminated Chlorella sp. differs from waterborne
      Cd toxicity both in terms of the most sensitive endpoint (growth vs survival) and
      the relationship between toxicity and bioaccumulation. Unlike Cd toxicity through
      water exposure, Cd bioaccumulation by H. azteca cannot, therefore, be used to
      infer toxicity of Cd in a diet of Chlorella sp. Although the concentration of Cd
      in the algal culture medium that ultimately reduced growth of H. azteca in the
      present study was higher than Cd in water, which caused mortality to H. azteca in
      water-only tests during previous studies, further research regarding the
      contribution of dietary Cd to overall Cd toxicity is needed to verify that water
      quality guidelines and risk assessments based on water-only exposures are fully
      protective.

PMID- 16986811
TI  - Toxicity models of pulsed copper exposure to Pimephales promelas and Daphnia
      magna.
AB  - Semiempirical models are useful for interpreting the response of aquatic
      organisms to toxicants as a function of exposure concentration and duration. Most
      applications predict cumulative mortality at the end of the test for constant
      exposure concentrations. Summary measures, such as the median lethal
      concentration, are then estimated as a function of concentration. Real-world
      exposures are not constant. Effects may depend on pulse timing, and cumulative
      analysis based only on integrated exposure concentration is not sufficient to
      interpret results. We undertook a series of pulsed-exposure experiments using
      standard toxicological protocols and interpreted the results (mortality, biomass,
      and reproduction) using a dynamic generalization of a Mancini/Breck--type model
      that includes two compartments, one for internal concentration as a function of
      exposure and one for site-of-action concentration or accumulated damage as a
      function of the internal dose. At exposure concentrations near the effects level,
      the model explained approximately 50% of the variability in the observed time
      history of survival, 43% of the change in biomass, and 83% of the variability in
      net reproduction. Unexplained variability may result from differences in organism
      susceptibility, amplified by the effects of small sample sizes in standard tests.
      The results suggest that response is sensitive to prior conditions and that
      constant-exposure experiments can underestimate the risk from intermittent
      exposures to the same concentration. For pulsed exposures, neither the average
      nor the maximum concentration alone is an adequate index of risk, which depends
      on both the magnitude, duration, and timing of exposure pulses. Better
      understanding about the impacts of pulsed exposures will require use of
      experimental protocols with significantly greater numbers of replicates.

PMID- 16986812
TI  - Rapid response teams reduce mortality rates, complications.

PMID- 16986813
TI  - Controlling blood sugar before surgery helps reduce infections, mortality rates.
AB  - Hospitals should expand point-of-care testing programs for blood sugar levels for
      all patients--including as a pre-operating screening program for hyperglycemia-
      because testing costs are so low and the potential for quality improvement and
      cost savings are so high.

PMID- 16986814
TI  - Executive rounding program improves communication, performance.
AB  - A patient safety executive rounding program at St. Charles Hospital, Port
      Jefferson, NY, has united staff and helped to identify a number of performance
      issues. The success of the program has even surprised top administrators who
      pushed to have it implemented. Each month, teams of executive staff and
      department heads make rounds through all areas of the hospital, talking with
      staff, identifying problem areas and noting best practices that could be used in
      other departments.

PMID- 16986815
TI  - Depressive symptomatology in the immediate postnatal period: identifying maternal
      characteristics related to true- and false-positive screening scores.
AB  - OBJECTIVE: To determine whether true- and false-positive postnatal depression
      screening scores can be distinguished during the early postpartum period by
      examining characteristic differences between 2 groups: 1) women with depressive
      symptomatology at 1 week postpartum who continue to exhibit symptoms at 8 weeks
      postpartum, compared with those who do not; and 2) women with depressive
      symptomatology at 8 weeks postpartum who previously exhibited symptoms at 1 week
      postpartum, compared with those who did not. METHOD: As part of a longitudinal
      postpartum depression study, a population-based sample of 594 women completed
      mailed questionnaires at 1, 4, and 8 weeks postpartum. RESULTS: Among women with
      depressive symptomatology at 1 week postpartum, diverse variables distinguished
      between those whose symptoms persisted or remitted at 8 weeks. These variables
      included recent immigrant status, psychiatric history, premenstrual symptoms,
      vulnerable personality, low self-esteem, child abuse history, and insufficient
      support. Variables that distinguished between women with depressive
      symptomatology at 8 weeks postpartum who previously exhibited symptoms at 1 week
      postpartum and those who did not included vulnerable personality, life stressors,
      perceived stress, insufficient support, and partner conflict. CONCLUSIONS: To
      address both the benefits and potential harms of early screening, positive
      screening scores on the Edinburgh Postnatal Depression Scale should also include
      an assessment of each individual woman's risk for postpartum depression and (or)
      chronic major depression.

PMID- 16986816
TI  - Obesity in bipolar disorder and major depressive disorder: results from a
      national community health survey on mental health and well-being.
AB  - OBJECTIVE: We aimed to ascertain the prevalence of obesity in individuals with a
      mood disorder (MD) (that is, bipolar disorder or major depressive disorder),
      compared with the general population. We further aimed to examine the likelihood
      of an association between obesity and MD, while controlling for the influence of
      sociodemographic variables. METHOD: The analysis was based on data from
      Statistics Canada's Canadian Community Health Survey: Mental Health and Well
      Being (CCHS 1.2), conducted in 2002. The sample (n = 36 984; > or = aged 15
      years) was drawn from the Canadian household-dwelling population. The CCHS used
      diagnostic criteria outlined in the DSM-IV to screen respondents. RESULTS:
      Individuals with a lifetime history of MD were more likely to be obese (body mass
      index [BMI] > 30) than were individuals without lifetime MD (19%, compared with
      15%, respectively; P < 0.001). In sex-specific multivariate analysis, lifetime MD
      was associated with elevated odds of obesity in female respondents (95%CI, 1.03
      to 1.46, odds ratio 1.22), but not in male respondents. Antipsychotic
      pharmacotherapy was also associated with obesity. CONCLUSIONS: This is the first
      Canadian epidemiologic investigation to specifically evaluate anthropometric
      indices and associated factors in people with MDs. The results herein supplement
      substantial clinical evidence documenting the association between MDs and stress
      sensitive somatic disorders (for example, obesity). These data also underscore
      the metabolic consequences of some psychotropic agents.

PMID- 16986817
TI  - Agreement between staff and service users concerning the clientele's mental
      health needs: a Quebec study.
AB  - OBJECTIVES: This article examines the differences found between clientele with
      severe mental health problems and their key health workers in terms of assessing
      service users' needs in 6 Quebec service areas. METHOD: We questioned 165 pairs
      of users and staff, using the Camberwell Assessment of Needs questionnaire. The
      profile of serious and overall problems encountered by clientele from each of the
      sites was compared. RESULTS: The sites with the greatest degree of user-staff
      agreement in identifying problems were also the ones where users considered that
      local services best met their needs. CONCLUSIONS: The study demonstrated that, in
      needs assessment, major differences exist between the perceptions of users and
      their key workers in the various sites. These differences can be explained in
      part by users' individual characteristics, by types of needs, by local
      particularities, and by service use.

PMID- 16986818
TI  - Sedative hypnotic use in Alberta.
AB  - OBJECTIVE: Benzodiazepines and similar sedative-hypnotics (BDZ-SSHs) are
      associated with both beneficial and adverse effects. Pharmacoepidemiologic data
      describing the use of these medications in contemporary Canadian populations has
      not been readily available. Our objective was to examine the hypothesis that
      increasing use of antidepressant medications for anxiety and mood disorders
      during the past decade led to less frequent use of BDZ-SSH medications. METHOD:
      We used data from an Alberta Mental Health Survey to describe the pattern of BDZ
      SSH use and to estimate provincial and health region frequencies of use. We
      supplemented the data with pharmacy dispensing data from IMS Health. RESULTS: The
      frequency of use was comparable to that reported in previous studies.
      Unexpectedly, in the survey data, we observed trends suggesting regional
      variation both in the frequency and pattern of use. Examination of prescription
      dispensing data confirmed this pattern. Clinical factors, including the use of
      other psychotropic medications and psychiatric diagnoses, were strongly
      associated with BDZ-SSH use. Among the drugs examined, zopiclone had the highest
      frequency of use. Prescription dispensing data confirmed that the frequency of
      zopiclone use in Alberta is higher than that in most other provinces.
      CONCLUSIONS: This descriptive study generates several new research questions and
      provides benchmarks for future pharmacoepidemiologic monitoring.

PMID- 16986819
TI  - Androgen treatment of depressive symptoms in older men: a systematic review of
      feasibility and effectiveness.
AB  - OBJECTIVE: To determine the feasibility and effectiveness of androgen treatment
      of depressive symptoms in older men. METHOD: We searched MEDLINE, PsycINFO, Eric,
      HealthStar, and the Cochrane Database of Systematic Reviews for potentially
      relevant articles. The bibliographies of relevant articles were searched for
      additional references and experts were consulted. Seventeen reports (8 open and
      12 randomized trials; 3 articles reported studies of 2 designs) met the following
      inclusion criteria: original investigation; published in English or French, use
      of acknowledged criteria or scale for depression, and open or randomized trial of
      androgen treatment. Four criteria assessed study validity: randomization, double
      blinding, comparability of treatment and control groups at baseline, and
      description of dropouts. We abstracted, tabulated, and compared information from
      each article. RESULTS: Most studies had methodological limitations. With regard
      to feasibility, there were few reported withdrawals due to adverse events. With
      regard to effectiveness, 6 of 8 open trials had positive results, and 5 of 12
      randomized trials had positive results, although 1 was equivocal. However,
      testosterone was combined with antidepressant medication in 3 of these positive
      randomized trials. Only 2 open trials enrolled subjects whose mean age was 60
      years or over. One had positive results, and the other had negative results.
      CONCLUSION: Androgen therapy may be feasible in the short term, but there is
      little evidence that it is an effective treatment for depressive symptoms in
      older men.

PMID- 16986820
TI  - Systematic overview of drug interactions with antidepressant medications.
AB  - OBJECTIVE: Antidepressants are commonly used drugs with potential for numerous
      drug interactions. This study aims to systematically review the literature on
      drug interactions with antidepressants. METHODS: We searched MEDLINE (1966 to
      November 2003) and EMBASE (1980 to 2003), using the heading drug interactions
      combined with individual antidepressant names. We restricted searches to English
      language articles and human studies. We screened drug interaction texts and
      review articles for relevant studies. We included articles reporting original
      human data on drug interactions with antidepressants commonly used in North
      America. Articles were independently evaluated by 2 reviewers on clinical effect,
      clinical significance, and quality of evidence. Discrepancies were resolved by
      consensus. RESULTS: There were 904 eligible interactions, involving 9509
      patients, for a total of 598 summary interactions. Of these, 439 (73%)
      demonstrated an interaction, 148 (25%) had no effect, and 11 (2%) had conflicting
      evidence. For 510 interactions (85%), the quality of evidence was poor. It was
      fair for 67 (11%) interactions and good for 10 (2%) interactions. There were no
      interactions with excellent quality of evidence. There were 145 (24%)
      interactions of major clinical significance. These were predominantly
      hypertensive emergencies and serotonin syndrome. Most interacting drugs had
      central nervous system (CNS) activity. As expected, monoamine oxidase inhibitors
      (MAOIs) appear to be the most problematic family in terms of potential for
      serious drug interactions. CONCLUSIONS: Drug interactions with antidepressants
      are an important cause for concern, but this concern is based primarily on poor
      evidence. We recommend caution when combining antidepressants with other CNS
      drugs, particularly when coadministering MAOIs with other substances.

PMID- 16986821
TI  - Building a better model: an introduction to structural equation modelling.
AB  - Confirmatory factor analysis (CFA) and structural equation modelling (SEM) are
      powerful extensions of path analysis, which was described in a previous article
      in this series. CFA differs from the more traditional exploratory factor analysis
      in that the relations among the variables are specified a priori, which permits
      more powerful tests of construct validity for scales. It can also be used to
      compare different versions of a scale (for example, English and French) and to
      determine whether the scale performs equivalently in different groups (for
      example, men and women). SEM expands on path analysis by allowing paths to be
      drawn between latent variables (which, in other techniques, are called factors or
      hypothetical constructs), that is, variables that are not seen directly but,
      rather, through their effect on observable variables, such as questionnaires and
      behavioural measures. Each latent variable and its associated measured variables
      form small CFAs, with the added advantage that the correlations among the
      variables can be corrected for the unreliability of the measures.

PMID- 16986822
TI  - The parent interview for child symptoms: a situation-specific clinical research
      interview for attention-deficit hyperactivity and related disorders.
AB  - OBJECTIVE: To describe the properties of a semistructured research interview of
      parents designed to evaluate attention-deficit hyperactivity disorder (ADHD) and
      related psychopathology. METHOD: We examined interrater reliability in 48
      videotaped interviews randomly selected from a large clinic sample. We examined
      convergence of the Parent Interview for Child Symptoms (PICS) and Conners' Parent
      Rating Scale (CPRS) scores in 594 clinic-referred cases and 26 control subjects,
      comparing the groups generated by cross-tabulation on measures of intelligence,
      academic achievement, and inhibitory control. RESULTS: Intraclass correlation
      coefficients for symptom scores of ADHD, oppositional defiant disorder (ODD), and
      conduct disorder (CD) were excellent. We found good reliability for diagnoses of
      ADHD (e = 0.73) and CD (kappa = 0.73) and excellent reliability for the diagnosis
      of ODD (kappa = 0.80). Two-thirds of cases were classified similarly on the PICS
      and the CPRS. Greater impairment in inhibitory control was observed in cases
      identified as ADHD by the PICS, compared with those identified by the CPRS-ADHD
      index. CONCLUSIONS: The PICS displays good reliability and validity, indicating
      that a balance between clinical applicability and reliability can be achieved in
      the development of clinical research instruments.

PMID- 16986823
TI  - Re: Day treatment for personality disorders.

PMID- 16986824
TI  - Near-UV resonant two-photon ionization spectroscopy of gas phase guanine:
      evidence for the observation of three rare tautomers.
AB  - In light of a recently published study on the IR spectroscopy of guanine in He
      droplets (Choi, M. Y.; Miller, R. E. J. Am. Chem. Soc. 2006, 128, 7320), the
      present letter proposes a new interpretation of the resonant two-photon
      ionization (R2PI) experiments on gas phase guanine, which is supported by quantum
      chemistry calculations. Whereas He droplet experiments detect the most stable
      forms, only one of these forms is observed (very marginally) in the R2PI
      spectrum, which is actually dominated by three less stable "rare" tautomers,
      whose stabilities lie in the 3-7 kcal/mol range. The absence of the most stable
      forms in the R2PI spectrum suggests that a tautomer-dependent ultrafast
      relaxation process takes place in the excited state of these stable tautomers.
      The present reinterpretation modifies qualitatively the picture of the excited
      state of guanine tautomers and should contribute to the understanding of the
      deactivation mechanisms taking place in the excited state of DNA bases.

PMID- 16986825
TI  - Field-resolved coherent Raman spectroscopy of high frequency vibrational
      resonances.
AB  - Electric fields of coherent Raman signals are resolved with sensitivity for high
      frequency vibrational resonances utilizing a four-pulse, trapezoidal beam
      geometry in a diffractive optic-based interferometer. Our experiments show that
      the heterodyne detected signal phase is stabilized for particular terms in the
      third-order response function by the cancellation of inter-pulse phases. The C-H
      stretching modes of cyclohexane and benzene are studied under two polarization
      conditions. The temporal profiles of signal fields for cyclohexane exhibit a low
      frequency recurrence due to the interference between the signals associated with
      the symmetric and asymmetric C-H stretching modes. In contrast, the
      electronically nonresonant polarizability response of benzene gives rise to a
      significant broadband signal component in addition to that associated with its C
      H vibrational resonance. Time-frequency shapes of the Raman signal fields are
      strongly dependent on the properties of the liquid and the polarizations of the
      laser pulses.

PMID- 16986826
TI  - Dynamics of nonadiabatic chemical reactions.
AB  - New methods are proposed to treat nonadiabatic chemical dynamics in realistic
      large molecular systems by using the Zhu-Nakamura (ZN) theory of curve-crossing
      problems. They include the incorporation of the ZN formulas into the Herman-Kluk
      type semiclassical wave packet propagation method and the trajectory surface
      hopping (TSH) method, formulation of the nonadiabatic transition state theory,
      and its application to the electron transfer problem. Because the nonadiabatic
      coupling is a vector in multidimensional space, the one-dimensional ZN theory
      works all right. Even the classically forbidden transitions can be correctly
      treated by the ZN formulas. In the case of electron transfer, a new formula that
      can improve the celebrated Marcus theory in the case of normal regime is obtained
      so that it can work nicely in the intermediate and strong electronic coupling
      regimes. All these formulations mentioned above are demonstrated to work well in
      comparison with the exact quantum mechanical numerical solutions and are expected
      to be applicable to large systems that cannot be treated quantum mechanically
      numerically exactly. To take into account another quantum mechanical effect,
      namely, the tunneling effect, an efficient method to detect caustics from which
      tunneling trajectories emanate is proposed. All the works reported here are the
      results of recent activities carried out in the author's research group. Finally,
      the whole set of ZN formulas is presented in Appendix.

PMID- 16986827
TI  - Absence of a signature of aqueous I(2P(1/2)) after 200-nm photodetachment of I
      (aq).
AB  - Ultrafast pump-broadband probe spectroscopy was used to study the transient
      photoproducts following 200-nm photodetachment of I(-)(aq). Resonant detachment
      at 200 nm in the second charge-transfer-to-solvent (CTTS) band of I(-)(aq) is
      expected to produce an electron and iodine in its spin-orbit excited state,
      I*((2)P(1/2)). The transients in solution following photodetachment were probed
      from 200 to 620 nm. Along with strong absorption in the visible region due to
      solvated electrons and a strong bleach of the I(-)(aq) ground-state absorption, a
      weaker transient absorption near 260 nm was observed that is consistent with a
      previously assigned ground-state I((2)P(3/2)) charge-transfer band. However, no
      evidence was found for an equivalent I*(aq) charge-transfer absorption, and
      I((2)P(3/2)) was produced within the instrument response. This suggests either
      that I* is electronically relaxed in less than 300 fs or that excitation in the
      second CTTS band does not in fact lead to I*. The consequences for previous
      experimental work where I*(aq) production has been postulated, as well as for
      halogen electron ejection mechanisms, are discussed. In addition, the broad
      spectral coverage of this study reveals in the bleach recovery the rapid cooling
      of the solvent surrounding the re-formed iodide after geminate recombination of
      the iodine with the solvated electron.

PMID- 16986828
TI  - Bifunctional charge transfer operated fluorescent probes with acceptor and donor
      receptors. 1. Biphenyl-type sensor molecules with protonation-induced anti-energy
      gap rule behavior.
AB  - On the basis of biphenyl (b) type molecules bpb-R substituted with a 2,2':6',2' '
      terpyridine acceptor (bp) and either amino-type donor receptors (R =
      dimethylamino (DMA), A15C5 = monoaza-15-crown-5) or nonbinding substituents (R =
      CF(3), H, OMe) of various donor strengths, we developed a family of charge
      transfer (CT) operated monofunctional and bifunctional fluorescent sensors for
      protons and metal ions. These molecules are designed to communicate the
      interaction of an analyte with the acceptor and the donor receptor differing in
      basicity and cation selectivity by clearly distinguishable spectral shifts and
      intensity modulations in absorption and in emission as well as in fluorescence
      lifetime. From the dependence of the fluorescence spectra, fluorescence quantum
      yields, and fluorescence lifetimes of bpb-R on solvent polarity and proton
      concentration, the photophysics of bpb-R and their protonated analogues can be
      shown to be governed by the relaxation to a CT state of forbidden nature and by
      the switching between anti-energy and energy gap law type behaviors. This
      provides the basis for analytically favorable red shifted emission spectra in
      combination with comparatively high fluorescence quantum yields. Accordingly, bpb
      H and bpb-OMe are capable of ratiometric emission signaling of protons. bpb-DMA
      reveals a protonation-induced ON-OFF-ON switching of its emission.

PMID- 16986829
TI  - Bifunctional charge transfer operated fluorescent probes with acceptor and donor
      receptors. 2. Bifunctional cation coordination behavior of biphenyl-type sensor
      molecules incorporating 2,2':6',2' '-terpyridine acceptors.
AB  - Based on donor (D)-acceptor (A) biphenyl (b) type molecules, a family of
      fluorescent reporters with integrated acceptor receptors and noncoordinating and
      coordinating donor substituents of varying strength has been designed for
      ratiometric emission sensing and multimodal signaling of metal ions and protons.
      In part 2 of this series on such charge transfer (CT) operated mono- and
      bifunctional fluorescent devices, the cation coordination behavior of the sensor
      molecules bpb-R equipped with a proton- and cation-responsive 2,2':6',2' '
      terpyridine (bp) acceptor and either amino-type donor receptors (R = DMA, A15C5 =
      monoaza-15-crown-5) or nonbinding substituents (R = CF(3), H, OMe) is
      investigated employing the representative metal ions Na(I), Ca(II), Zn(II),
      Hg(II), and Cu(II) and steady-state and time-resolved fluorometry. The bpb-R
      molecules, the spectroscopic behavior and protonation behavior of which have been
      detailed in part 1 of this series, present rare examples for CT-operated
      bifunctional fluorescent probes that can undergo consecutive and/or simultaneous
      analyte recognition. The analyte-mediated change of the probes' intramolecular CT
      processes yields complexation site- and analyte-specific outputs, i.e.,
      absorption and fluorescence modulations in energy, intensity, and lifetime. As
      revealed by the photophysical studies of the cation complexes of these
      fluoroionophores and the comparison to other neutral and charged D-A biphenyls,
      the spectroscopic properties of the acceptor chelates of bpb-R and A- and D
      coordinated bpb-R are governed by CT control of an excited-state barrier toward
      formation of a forbidden charge transfer state, by the switching between
      analytically favorable anti-energy and common energy gap law type behavior, and
      by the electronic nature of the ligated metal ion. This accounts for the
      astonishingly high fluorescence quantum yields of the acceptor chelates of bpb-R
      equipped with weak or medium-sized donors and the red emission of D- and A
      coordinated bpb-R observed for nonquenching metal ions.

PMID- 16986830
TI  - Electroabsorption spectroscopy of 6-hydroxyquinoline doped in polymer films:
      Stark shifts and orientational effects.
AB  - Stark absorption spectroscopy was applied to 6-hydroxyquinoline (6-HQ) doped in
      polymer films of poly(methyl methacrylate) (PMMA) and poly(vinyl alcohol) (PVA)
      at temperatures of 50-300 K. The electroabsorption (E-A) spectrum of 6-HQ
      markedly depends on temperature in a PMMA film. The polarization dependence as
      well as the temperature dependence of the E-A spectra reveals that 6-HQ is
      oriented along the direction of the applied electric field at room temperature in
      a PMMA film. As the temperature becomes lower, the field-induced orientation of 6
      HQ is restricted, and only the Stark shift induced by a change in electric dipole
      moment and in molecular polarizability is observed. On the other hand, E-A
      spectra of 6-HQ doped in a PVA film are essentially independent of temperature,
      suggesting that 6-HQ is not oriented along the electric field even at room
      temperature in PVA. These results show that the molecular motion of 6-HQ in a
      polymer film is very sensitive to the microenvironment of the surrounding matrix.

PMID- 16986831
TI  - Nitric oxide decomposition on small rhodium clusters, Rh(n)+/-.
AB  - The decomposition of nitric oxide on small charged rhodium clusters Rh(n)(+/-) (6
      < n < 30) has been investigated by Fourier transform ion cyclotron resonance mass
      spectrometry. For both cationic and anionic naked clusters, the rates of reaction
      with NO increase smoothly with cluster size in the range studied without the
      dramatic size-dependent fluctuations often associated with the reactions of
      transition-metal clusters. The cationic clusters react significantly faster than
      the anions and both exhibit rate constants exceeding collision rates calculated
      by average dipole orientation theory. Both the approximate magnitude and the
      trends in reactivity are modeled well by the surface charge capture model
      recently proposed by Kummerlowe and Beyer. All clusters studied here exhibit
      pseudo-first-order kinetics with no sign of biexponential kinetics often
      interpreted as evidence for multiple isomeric structures. Experiments involving
      prolonged exposure to NO have revealed interesting size-dependent trends in the
      mechanism and efficiency of NO decomposition: For most small clusters (n < 17),
      once two NO molecules are coadsorbed on a cluster, N(2) is evolved, generating
      the corresponding dioxide cluster. By analogy with experiments on extended
      surfaces, this observation is interpreted in terms of the dissociative adsorption
      of NO in the early stages of reaction, generating N atoms that are mobile on the
      surface of the cluster. For clusters where n < 13, this chemistry, which occurs
      independently of the cluster charge, repeats until a size-dependent, limiting
      oxygen coverage is achieved. Following this, NO is observed to adsorb on the
      oxide cluster without further N(2) evolution. For n = 14-16 no single end-point
      is observed and reaction products are based on a small range of oxide structures.
      By contrast, no evidence for N(2) production is observed for clusters n = 13 and
      n > 16, for which simple sequential NO adsorption dominates the chemistry.
      Interestingly, there is no evidence for the production of N(2)O or NO(2) on any
      of the clusters studied. A simple general mechanism is proposed that accounts for
      all observations. The detailed decomposition mechanisms for each cluster exhibit
      size (and, by implication, structure) dependent features with Rh(13)(+/-)
      particularly anomalous by comparison with neighboring clusters.

PMID- 16986832
TI  - Renner-Teller effect in C2H2+(X2Pi u) studied by rotationally resolved zero
      kinetic energy photoelectron spectroscopy.
AB  - The Renner-Teller effect in C(2)H(2)(+)(X(2)Pi(u)) has been studied by using zero
      kinetic energy (ZEKE) photoelectron spectroscopy and coherent extreme ultraviolet
      (XUV) radiation. The rotationally resolved vibronic spectra have been recorded
      for energies up to 2000 cm(-1) above the ground vibrational state. The C triple
      bond C symmetric stretching (upsilon(2)), the CCH trans bending (upsilon(4)), and
      the CCH cis bending (upsilon(5)) vibrational excitations have been observed. The
      assigned vibronic bands are 4(1)(1)(kappa(2)Sigma(u)(+))(hot band),
      4(1)(0)(mu/kappa(2)Sigma (u)(-/+)), 5(1)(0)(mu/kappa(2)Sigma (g)(+/-)), and
      4(2)(0)(mu(2)Pi(u)), 4(2)(0)(kappa(2)Pi(u)), 4(1)(0)5(1)(0) (mu(2)Pi(g)),
      0(0)(0)(X(2)Pi(u)), and 2(1)(0)(X(2)Pi(u)). The Renner-Teller parameters, the
      harmonic frequencies, the spin-orbit coupling constants, and the rotational
      constants for the corresponding vibronic bands have been determined by fitting
      the spectra with energy eigenvalues from the Hamiltonian that considers
      simultaneously Renner-Teller coupling, vibrational energies, rotational energies,
      and spin-orbit coupling interaction.

PMID- 16986833
TI  - Anisotropic interaction and stereoreactivity in a chemi-ionization process of OCS
      by collision with He*(2(3)S) metastable atoms.
AB  - Ionic-state-resolved collision energy dependence of Penning ionization cross
      sections for OCS with He*(2(3)S) metastable atoms was measured in a wide
      collision energy range from 20 to 350 meV. Anisotropic interaction potential for
      the OCS-He*(2(3)S) system was obtained by comparison of the experimental data
      with classical trajectory simulations. It has been found that attractive
      potential wells around the O and S atoms are clearly different in their
      directions. Around the O atom, the collinear approach is preferred (the well
      depth is ca. 90 meV), while the perpendicular approach is favored around the S
      atom (the well depth is ca. 40 meV). On the basis of the optimized potential
      energy surface and theoretical simulations, stereo reactivity around the O and S
      atoms was also investigated. The results were discussed in terms of anisotropy of
      the potential energy surface and the electron density distribution of molecular
      orbitals to be ionized.

PMID- 16986834
TI  - Excited-state properties and emission spectra of nonplanar heterocyclic
      helicenes.
AB  - We discuss the electron-vibration coupling in mono-aza-[5]helicenes on the basis
      of a Franck-Condon analysis and density functional theory (DFT) calculations of
      the fluorescence and phosphorescence spectra measured in ethanol. The geometries
      of the initial states were obtained from time-dependent DFT (S(1)) and
      unrestricted DFT (T(1)) excited-state optimizations. In general, the position of
      the nitrogen atom has only a minor impact on the vibronic fine-structure in both
      absorption and emission. The shapes of the emission spectra from the lowest
      singlet and triplet states are found to be determined by contributions from
      multiple normal modes. The results of the calculations demonstrate how the
      interplay among these normal modes results in qualitatively and quantitatively
      different spectra for fluorescence and phosphorescence.

PMID- 16986835
TI  - Effect of hydroxylic solvent on the fluorescence behavior of some bioactive 9-oxo
      imidazo[1,2-a]purine derivatives.
AB  - The spectral and photophysical behavior of four fluorescent 9-oxo-imidazo[1,2
      a]purine derivatives containing pyridyl, pyridylphenyl, phenyl, and biphenylyl
      substituents at the C(6) position of the tricyclic skeleton is described. The
      studies were performed in several aprotic and protic organic solvents using
      absorption spectroscopy as well as steady-state and time-resolved fluorescence
      spectroscopy. The results are also presented of TDDFT calculations on singlet
      singlet excitation energies and oscillator strengths for two models of 9-oxo
      imidazo[1,2-a]purine, with phenyl or pyridyl substituents, both in the gas phase
      and in methanol solution. While the derivatives with aryl substituents did not
      show any significant dependence of their static and dynamic fluorescence
      properties on the nature of the solvent, the compounds containing a pyridine
      residue exhibited a remarkable reduction of their fluorescence quantum yields and
      lifetimes in the alcoholic solutions. The solute-solvent hydrogen-bonding
      interaction in the first excited singlet state is responsible for the fast
      radiationless decay rates determined for pyridyl- and pyridylphenyl-substituted
      compounds in protic solvents. The results of experimental and theoretical studies
      show that the hydrogen of the alcohols' hydroxyl group and the nitrogen atom of
      the pyridine moiety are involved in the interaction. The fluorescence-quenching
      experiments performed for the pyridyl-substituted 9-oxo-imidazo[1,2-a]purine
      derivative using trifluoroethanol, methanol, and butanol as quenchers revealed
      that the quenching efficiencies, expressed by the Stern-Volmer quenching
      constants, correlate with the H-bond donating abilities of the alcohols. The
      quenching is a dynamic process, and the H-bonded complex formed is
      nonfluorescent. The experimentally determined and the calculated values of the
      dipole moment change associated with the electronic excitation indicate that the
      excited S(1) states of all of the molecules studied in this work have an
      intramolecular charge-transfer character and that electronic charge is
      transferred to the C(6) substituent upon excitation. Thus, the ability of the
      pyridyl substituent nitrogen atom to act as an H-bond acceptor in the excited
      S(1) state is enhanced. The 6-pyridyl-9-oxo-imidazo[1,2-a]purine presents a novel
      fluorophore, which, besides its medical applications, may be useful as a sensor
      of hydroxyl groups in microorganized systems.

PMID- 16986836
TI  - Molecular structure, infrared spectrum, and photochemistry of squaric acid
      dimethyl ester in solid argon.
AB  - Squaric acid dimethyl ester (C(6)O(4)H(6); 3,4-dimethoxycyclobut-3-ene-1,2-dione;
      DCD) was studied by matrix isolation infrared spectroscopy and by density
      functional theory (B3LYP) and ab initio (MP2) calculations with the 6-31++G(d,p)
      and 6-311++G(d,p) basis sets. Three conformers of the compound were theoretically
      predicted. The two most stable conformers were identified in low-temperature
      argon matrixes and the energy gap between them was determined. The trans-trans
      conformer (C(2)(v)) was found to be more stable than the cis-trans form (C(s)) by
      4.2 kJ mol(-1), in consonance with the theoretical predictions (MP2 calcd = 3.9
      kJ mol(-1)). In situ broadband UV irradiation (lambda > 337 nm) of the matrix
      isolated compound was found to induce the ring-opening reaction leading to
      production of the bisketene, 2,3-dimethoxybuta-1,3-diene-1,4-dione as well as the
      trans-trans --> cis-trans conformational isomerization. The latter
      phototransformation allowed separation of the infrared spectra of the two
      conformers initially trapped into a low-temperature matrix. Upon higher energy
      irradiation (lambda > 235 nm), the main observed photoproducts were CO and deltic
      acid dimethyl ester (C(5)O(3)H(6); 2,3-dimethoxycycloprop-2-en-1-one), the latter
      being obtained in two different conformations (trans-trans and cis-trans).
      According to the experimental data, deltic acid dimethyl ester is produced by
      decarbonylation of the initially formed bisketene and not by direct CO extrusion
      from DCD.

PMID- 16986837
TI  - Reactions of 1-hydroxy-1-methylethyl radicals with NO2-: time-resolved electron
      spin resonance.
AB  - The reaction of the alpha-hydroxyalkyl radical of 2-propanol (1-hydroxy-1
      methylethyl radical) with nitrite ions was characterized. A product of the
      reaction was assigned as the adduct nitro radical anion, [HO-C(CH(3))(2)NO(2)](*
      ). This radical was identified using time-resolved electron spin resonance
      (TRESR). The radical's magnetic parameters, the nitrogen hyperfine coupling
      constant (a(N) = 26.39 G), and its g-factor (2.0052) were the same as those of
      the nitro radical anion previously discovered in (*)OH spin-trapping experiments
      with the aci-anion of (CH(3))(2)CHNO(2). Production of [HO-C(CH(3))(2)NO(2)](*-)
      was determined to be 38% +/- 4% of the reaction of (CH(3))(2)C(*)-OH with
      nitrite. The reason why this fraction was less than 100% was rationalized by
      invoking the competitive addition at oxygen, which forms [HO-C(CH(3))(2)ONO](*-),
      followed by a rapid loss of (*)NO. Furthermore, by taking this mechanism into
      account, the bimolecular rate constant for the total reaction of (CH(3))(2)C(*)
      OH with nitrite at reaction pH 7 was determined to be 1.6 x 10(6) M(-1) s(-1),
      using both decay traces of (CH(3))(2)C(*)-OH and growth traces of [HO
      C(CH(3))(2)NO(2)](*-). This correspondence further confirms the nature of the
      reaction. The reaction mechanism is discussed with guidance by computations using
      density functional theory.

PMID- 16986839
TI  - Diffusion of HDO in pure and acid-doped ice films.
AB  - In these experiments, a few bilayers of D(2)O were vapor-deposited on a pure
      crystalline H(2)O ice film or an ice film doped with a small amount of HCl. Upon
      deposition, H/D isotopic exchange quickly converted the D(2)O layer into an HDO
      rich mixture layer. Infrared absorption spectroscopy followed the changes of the
      HDO from the initial HDO mixture layer to HDO isolated in the H(2)O ice film.
      This was possible because isolated HDO in H(2)O ice has a unique, sharp peak in
      the O-D stretch region that can be distinguished from the broad peak due to the
      initial HDO mixture layer. The absorbance of isolated HDO displayed first-order
      kinetics and was attributed to diffusion of HDO from the HDO-rich mixture layer
      into the underlying H(2)O ice film. While negligible diffusion was observed for
      pure ice films and for ice films with HCl concentrations up to 1 x 10(-4) mole
      fraction, diffusion of HDO occurred for higher concentrations of (2-20) x 10(-4)
      mole fraction HCl with a concentration-independent rate constant. The diffusion
      under these conditions followed Arrhenius behavior for T = 135-145 K yielding
      E(a) = 25 +/- 5 kJ/mol. The mechanism for the HDO diffusion involves either (i)
      molecular self-diffusion or (ii) long-range H/D diffusion by a series of multiple
      proton hop and orientational turn steps. While these spectroscopic results
      compare favorably with recent studies of molecular self-diffusion in low
      temperature ice films, the diffusion results from all the ice film studies at low
      temperatures (ca. T < 170 K) differ from earlier bulk ice studies at higher
      temperatures (ca. T > 220 K). A comparison and discussion of the various
      diffusion studies are included in this report.

PMID- 16986838
TI  - Secondary organic aerosol formation from limonene ozonolysis: homogeneous and
      heterogeneous influences as a function of NO(x).
AB  - Limonene has a high emission rate both from biogenic sources and from household
      solvents. Here we examine the limonene + ozone reaction as a source for secondary
      organic aerosol (SOA). Our data show that limonene has very high potential to
      form SOA and that NO(x) levels, O(3) levels, and UV radiation all influence SOA
      formation. High SOA formation is observed under conditions where both double
      bonds in limonene are oxidized, but those conditions depend strongly on NO(x). At
      low NO(x), heterogeneous oxidation of the terminal double bond follows the
      initial limonene ozonolysis (at the endocyclic double bond) almost immediately,
      making the initial reaction rate limiting. This requires a high uptake
      coefficient between ozone and the first-generation, unsaturated organic
      particles. However, at high NO(x), this heterogeneous processing is inhibited and
      gas-phase oxidation of the terminal double bond dominates. Although this
      chemistry is slower, it also yields products with low volatility. UV light
      suppresses production of the lowest volatility products, as we have shown in
      earlier studies of the alpha-pinene + ozone reaction.

PMID- 16986840
TI  - Kinetic and mechanistic study of the gas-phase reactions of a series of vinyl
      ethers with the nitrate radical.
AB  - NO(3) oxidation of methyl, ethyl, propyl, and butyl vinyl ethers has been studied
      under tropospheric conditions (atmospheric pressure and T = 293 +/- 3 K) in the
      LISA indoor simulation chamber. NO(3) was produced inside the reactor by thermal
      decomposition of N(2)O(5) previously added to the air-VOC mixture, and
      concentrations were monitored using FTIR spectrometry. All the kinetic
      experiments were carried out by relative rate technique using isoprene as
      reference compound, leading to the rate constants k(1) = (7.2 +/- 1.5) x 10(-13),
      k(2) = (13.1 +/- 2.7) x 10(-13), k(3) = (13.3 +/- 3.0) x 10(-13), and k(4) =
      (17.0 +/- 3.7) x 10(-13) cm(3) molecule(-1) s(-1) for methyl, ethyl, propyl, and
      butyl vinyl ethers, respectively. Main oxidation products have been identified
      like being formaldehyde and respectively methyl, ethyl, propyl, and butyl
      formates. Production yields of oxidation products were close to 50%. Oxygenated
      nitrates and peroxynitrates were also detected.

PMID- 16986841
TI  - Kinetic and equilibrium study on formic acid decomposition in relation to the
      water-gas-shift reaction.
AB  - Kinetics and equilibrium are studied on the hydrothermal decarbonylation and
      decarboxylation of formic acid, the intermediate of the water-gas-shift (WGS)
      reaction, in hot water at temperatures of 170-330 degrees C, to understand and
      control the hydrothermal WGS reaction. (1)H and (13)C NMR spectroscopy is applied
      to analyze as a function of time the quenched reaction mixtures in both the
      liquid and gas phases. Only the decarbonylation is catalyzed by HCl, and the
      reaction is first-order with respect to both [H(+)] and [HCOOH]. Consequently,
      the reaction without HCl is first and a half (1.5) order due to the unsuppressed
      ionization of formic acid. The HCl-accelerated decarbonylation path can thus be
      separated in time from the decarboxylation. The rate and equilibrium constants
      for the decarbonylation are determined separately by using the Henry constant
      (gas solubility data) for carbon monoxide in hot water. The rate constant for the
      decarbonylation is 1.5 x 10(-5), 2.0 x 10(-4), 3.7 x 10(-3), and 6.3 x 10(-2)
      mol(-1) kg s(-1), respectively, at 170, 200, 240, and 280 degrees C on the liquid
      branch of the saturation curve. The Arrhenius plot of the decarbonylation is
      linear and gives the activation energy as 146 +/- 3 kJ mol(-1). The equilibrium
      constant K(CO) = [CO]/[HCOOH] is 0.15, 0.33, 0.80, and 4.2, respectively, at 170,
      200, 240, and 280 degrees C. The van't Hoff plot results in the enthalpy change
      of DeltaH = 58 +/- 6 kJ mol(-1). The decarboxylation rate is also measured at 240
      330 degrees C in both acidic and basic conditions. The rate is weakly dependent
      on the solution pH and is of the order of 10(-4) mol kg(-1) s(-1) at 330 degrees
      C. Furthermore, the equilibrium constant K(CO2) = [CO(2)][H(2)]/[HCOOH] is
      estimated to be 1.0 x10(2) mol kg(-1) at 330 degrees C.

PMID- 16986842
TI  - Kinetics of the reactions of O(3P) with CCl2=CH2, (Z)-CHCl=CHCl, and CCl2=CCl2: a
      temperature dependence study.
AB  - Absolute rate coefficients for the gas-phase reactions of ground-state oxygen
      atoms with CCl(2)=CH(2) (1), (Z)-CHCl=CHCl (2) and CCl(2)=CCl(2) (3) have been
      measured directly using the fast flow discharge technique. The experiments were
      carried out under pseudo-first-order conditions with [O((3)P)](0) <<
      [chloroethene](0). The temperature dependences of the reactions of O((3)P) with
      CCl(2)=CH(2), (Z)-CHCl=CHCl and CCl(2)=CCl(2) were studied in the range 298-359
      K. The kinetic data obtained were used to derive the following Arrhenius
      expressions (in units of cm(3) molecule(-1) s(-1)): k(1) = (1.82 +/- 1.29) x 10(
      11) exp[-(12.63 +/- 0.97) x 10(3)/RT], k(2) = (1.56 +/- 0.92) x 10(-11) exp[
      (16.68 +/- 1.54) x 10(3)/RT], k(3) = (4.63 +/- 1.38) x 10(-11) exp[-(19.59 +/-
      3.21) x 10(3)/RT]. This is the first temperature dependence study of the
      reactions of O((3)P) atoms with (Z)-CHCl=CHCl and CCl(2)=CCl(2). All the rate
      coefficients display a positive temperature dependence and pressure independence,
      which points to the importance of the irreversibility of the addition mechanism
      for these reactions. The obtained rate coefficients are compared with previous
      studies carried out mainly at room temperature. The rates of addition of O atoms
      and OH radicals to the double bond of alkenes at 298 K are related by the
      expression: log k(OH) = 0.57278 log k(O(3P)) - 4.095. A correlation is presented
      between the reactivity of chloroethenes toward O atoms and the second-order
      perturbational term of the frontier molecular orbital theory which carries the
      contribution of the different atomic orbitals to the HOMO of the chloroethene. To
      a first approximation, this correlation allows room-temperature rate coefficients
      to be predicted within +/-25-30% of the measured values.

PMID- 16986843
TI  - Ultrasound-induced aqueous removal of nitric oxide from flue gases: effects of
      sulfur dioxide, chloride, and chemical oxidant.
AB  - The effects of sulfur dioxide (SO(2)), sodium chloride (NaCl), and
      peroxymonosulfate or oxone (2KHSO(5).KHSO(4).K(2)SO(4) with active ingredient,
      HSO(5)(-)) on the sonochemical removal of nitric oxide (NO) have been studied in
      a bubble column reactor. The initial concentration of NO studied ranged from
      about 500 to 1040 ppm. NaCl in the concentration range of 0.01-0.5 M was used as
      the electrolyte to study the effect of ionic strength. At the low NaCl
      concentration (0.01 M), the percent fractional removal of NO with initial
      concentration of 1040 ppm was enhanced significantly, while as the NaCl
      concentration increased, the positive effects were less pronounced. The presence
      of approximately 2520 ppm SO(2) in combination with 0.01 M NaCl further enhanced
      NO removal. However, with a NO initial concentration of 490 ppm, the addition of
      NaCl was detrimental to NO removal at all NaCl concentration levels. The
      combinative effect of sonication and chemical oxidation using 0.005-0.05 M oxone
      was also studied. While the lower concentrations of HSO(5)(-) enhanced NO removal
      efficiency, higher concentrations were detrimental depending on the initial
      concentration of NO. It was also demonstrated that in the presence of ultrasound,
      the smallest concentration of oxone was needed to obtain optimal fractional
      conversion of NO.

PMID- 16986844
TI  - Isotope fractionation of iron(III) in chemical exchange reactions using solvent
      extraction with crown ether.
AB  - This work reports on the chemical isotope fractionation of Fe(III) by a solvent
      extraction method with a crown ether of dicyclohexano-18-crown-6. The
      (56)Fe/(54)Fe and (57)Fe/(54)Fe ratios were analyzed by multiple-collector
      inductively coupled plasma mass spectrometry. We determined the dependence of the
      isotope enrichment factors (epsilon) on the strength of HCl. The relative
      deviation of the (56)Fe/(54)Fe ratios relative to the unprocessed material (10(4)
      epsilon(56)) increases from -15.3 to -6.3 with [HCl] increasing from 1.6 to 3.5
      mol/L. Likewise, 10(4) epsilon(57) increases from -22.8 to -9.6 under the same
      conditions. The correlation between epsilon(56) and epsilon(57) is mass dependent
      within the errors. The observed fractionation was broken down into the effects of
      competing extraction reactions and of a reaction between Fe(III) species
      (FeCl(2)(+) and FeCl(3)) in the aqueous phase. We found that the isotope
      fractionation between the Fe(III) species is mass dependent, which we confirmed
      by calculating the reduced partition function ratios.

PMID- 16986845
TI  - Reaction-path dynamics and theoretical rate constants for the CH(n)F(4-n) + O3 -
      > HOOO + CH(n-1)F(4-n) (n = 2,3) reactions.
AB  - We present a theoretical study of the hydrogen abstraction reactions from CH(3)F
      and CH(2)F(2) by an ozone molecule. The geometries and harmonic vibrational
      frequencies of all stationary points are calculated at the MPW1K, BHandHLYP, and
      MPWB1K levels of theory. The energies of all of the stationary points were
      refined by using both higher-level (denoted as HL) energy calculations and
      QCISD(T)/6-311++G(2df,2pd) calculations based on the optimized geometries at the
      MPW1K/6-31+G(d,p) level of theory. The minimum energy paths (MEPs) were obtained
      by the MPW1K/6-31+G(d,p) level of theory. Energetic information of the points
      along the MEPs is further refined by the HL method. The rate constants were
      evaluated on the basis of the MEPs from the HL level of theory in the temperature
      range 200-2500 K by using the conventional transition-state theory (TST), the
      canonical variational transition-state theory (CVT), the microcanonical
      variational transition-state theory (microVT), the CVT coupled with the small
      curvature tunneling (SCT) correction (CVT/SCT), and the microVT coupled with the
      Eckart tunneling correction (microVT/Eckart) based on the ab initio calculations.
      A general agreement was found among the TST, CVT, and microVT theories. The
      fitted three-parameter Arrhenius expressions of the calculated forward CVT/SCT
      and microVT/Eckart rate constants of the ozonolysis of fluoromethane are
      k(CVT/SCT)(T) = 2.76 x 10(-34)T(5.81)e((-13975/)(T)) and k(microVT/Eckart)(T) =
      1.15 x 10(-34)T(5.97)e((-14530.7/)(T)), respectively. The fitted three-parameter
      Arrhenius expressions of the calculated forward CVT/SCT and microVT/Eckart rate
      constants of the ozonolysis of difluoromethane are k(CVT/SCT)(T) = 2.29 x 10(
      36)T(6.42)e((-15451.6/)(T)) and k(microVT/Eckart)(T) = 1.31 x 10(-36)T(6.45)e((
      15465.8/)(T)), respectively.

PMID- 16986846
TI  - Fluoroolefins as peptide mimetics: a computational study of structure, charge
      distribution, hydration, and hydrogen bonding.
AB  - The design of peptide mimetic compounds is greatly facilitated by the
      identification of functionalities that can act as peptide replacements. The
      fluoroalkene moiety has recently been employed for that purpose. The purpose of
      this work is to characterize prototypical fluoroalkenes (fluoroethylene and 2
      fluoro-2-butene) with respect to key properties of peptides (amides) including
      structure, charge distribution, hydration, and hydrogen bonding. The results are
      compared to those obtained for model peptides (formamide, N-methylacetamide).
      Calculations have been carried out at the MP2 and B3LYP levels of theory with the
      6-311++G(2d,p) and 6-311++G(2d,2p) basis sets. The results suggest that the
      fluoroalkene is similar in steric requirements to a peptide bond but that there
      is less charge separation. Calculations of the hydration free energies with the
      PCM bulk continuum solvent model indicate that the fluoroalkene has much smaller
      hydration free energies than an amide but that the difference in solvation free
      energy for cis and trans isomers is comparable. In studies of complexes with
      water molecules, the fluoroalkene is found to engage in interactions that are
      analogous to backbone hydrogen-bonding interactions that govern many properties
      of natural peptides and proteins but with smaller interaction energies. In
      addition, key structural differences are noted when the fluoroalkene is playing
      the role of hydrogen-bond acceptor which may have implications in binding,
      aggregation, and conformational preferences in fluoroalkene peptidomimetics. The
      issue of cooperativity in hydrogen-bonding interactions in complexes with
      multiple waters has also been investigated. The fluoroalkene is found to exhibit
      cooperative effects that mirror those of the peptide but are smaller in
      magnitude. Thus, pairwise addivitity of interactions appears to more adequately
      describe the fluoroalkenes than the peptides they are intended to mimic.

PMID- 16986847
TI  - Ab initio investigations of the electric field dependence of the geometric and
      electronic structures of molecular wires.
AB  - Theoretical investigations on the typical molecular wire, polyacetylene, which
      bridges two chemically inert electrodes, have been carried out at the Hartree
      Fock level by incorporating the external electric field into the calculations.
      The results demonstrate that both the geometric and the electronic structures of
      the conjugated molecular wires are sensitive to the electric field. When the
      electric field increases, the carbon-carbon single bonds become shorter and the
      double bonds become longer, leading to a higher conjugation. The electric field
      reduces the HOMO-LUMO gap and increases the dipole moment. The spatial
      distributions of the molecular orbitals are used to analyze the electrical
      properties of the molecular wire. All of these features are more pronounced with
      increasing conjugation chain length. Quantitative correlations between most of
      these features and the electric field have been discussed as well.

PMID- 16986848
TI  - Conformational structure of gaseous 3-chloropropanoyl chloride by electron
      diffraction, normal coordinate analysis, and ab initio molecular orbital, and
      density functional theory calculations.
AB  - The molecular and conformational structures of 3-chloropropanoyl chloride
      (CH(2)Cl-CH(2)-C(=O)Cl) have been studied by using gas-phase electron diffraction
      (GED) data obtained at 22 degrees C (295 K) and ab initio molecular orbital (MO)
      and density functional theory (DFT) calculations up to the levels of MP4(SDQ) and
      B3LYP using larger basis sets. Normal coordinate calculations (NCA) taking into
      account nonlinear vibrational effects were also used in the analyses. The title
      compound may have up to four low-energy conformers in the gas phase, labeled
      according to the position of each of the two chlorine atoms in relation to the
      CCC propanoyl backbone, labeling the carbonyl chlorine torsion angle first: AA,
      AG, GG, and GA; where A is anti (ideal C-C-C-Cl torsion angle of approximately
      180 degrees) and G is gauche (ideal C-C-C-Cl torsion angle of approximately 60
      degrees). It has been judged from the experimental GED data and the theoretical
      calculations, as well as from previously published infrared (IR) studies on the
      molecule in both the liquid phase and in argon-trapped matrices at 10 K, that the
      gas phase consists of a mixture of at least three conformers: AA (most stable),
      AG, and GG, with the possibility of a smaller contribution (<10%) from the higher
      energy GA form. The GA conformer cannot be ruled out by the GED experimental
      data. Relevant structural parameter values obtained from the GED least-squares
      refinements, with calculated ab initio MO MP2/6-31+G(2d,p) values used as
      constraints, were as follows (AA values with estimated 2sigma uncertainties):
      Bond lengths (r(h1)): r(C-C(=O)) = 1.505(4) A, r(C-CH(2)Cl) = 1.520(4) A, r(C=O)
      = 1.197(4) A, r(C(=O)-Cl) = 1.789(3) A, and r(C-Cl) = 1.782(3) A. Bond angles
      (angle(h1)): angle CCC = 111.5(11) degrees , angle CCO = 127.0(5) degrees, angle
      CC(O)Cl = 112.5(3) degrees, and angle CCCl = 110.3(3) degrees. Torsion angles
      (phi(C-C) = phi(ClCCC)): for AA, phi(1)(C-C(O)) = phi(2)(C-CH(2)Cl) = 180 degrees
      (assumed for true C(s) symmetry); for AG, phi(1)(C-C(O)) = -140(5) degrees,
      phi(2)(C-CH(2)Cl) = 76(13) degrees; for GG, phi(1)(C-C(O)) = 46(8) degrees,
      phi(2)(C-CH(2)Cl) = 77(14) degrees; for GA, phi(1)(C-C(O)) = 67.9 degrees
      (assumed), phi(2)(C-CH(2)Cl) = 177.8 degrees (assumed). The non-AA conformers all
      have chiral C(1) symmetry with twice the statistical weight (multiplicity) of
      C(s). The MP2/6-31+G(2d,p) calculated composition (%) based on the zero-point
      energy (ZPE) corrected energy differences, and the statistical weights for
      conformers: AA/AG/GG/GA = 28/35/28/9 was assumed in the final GED refinement. The
      more recent literature concerning the title molecule, as well as for several
      related molecules, has been examined and a survey has been attempted in the
      present article. The new experimental results for 3-chloropropanoyl chloride are
      discussed and compared with the previously published findings.

PMID- 16986849
TI  - Ab initio/density functional theory and multichannel RRKM study for the ClO +
      CH2O reaction.
AB  - The potential energy surface for the CH(2)O + ClO reaction was calculated at the
      QCISD(T)/6-311G(2d,2p)//B3LYP/6-311G(d,p) level of theory. The rate constants for
      the lower barrier reaction channels producing HOCl + HCO, H atom, OCH(2)OCl, cis
      HC(O)OCl and trans-HC(O)OCl have been calculated by TST and multichannel RRKM
      theory. Over the temperature range of 200-2000 K, the overall rate constants were
      k(200-2000K) = 1.19 x 10(-13)T(0.79) exp(-3000.00/T). At 250 K, the calculated
      overall rate constant was 5.80 x 10(-17) cm(3) molecule(-1) s(-1), which was in
      good agreement with the experimental upper limit data. The calculated results
      demonstrated that the formation of HOCl + HCO was the dominant reaction channel
      and was exothermic by 9.7 kcal/mol with a barrier of 5.0 kcal/mol. When it
      retrograded to the reactants CH(2)O + ClO, an energy barrier of 14.7 kcal/mol is
      required. Furthermore, when HOCl decomposed into H + ClO, the energy required was
      93.3 kcal/mol. These results suggest that the decomposition in both the forward
      and backward directions for HOCl would be difficult in the ground electronic
      state.

PMID- 16986850
TI  - Theoretical insights, in the liquid phase, into the antioxidant mechanism-related
      parameters in the 2-monosubstituted phenols.
AB  - The paper describes a DFT/B3LYP study, in the liquid phase, [using the PCM
      continuum model] on the O-H bond dissociation enthalpy (BDE) and ionization
      energy (IE) parameter values of the 2-monosubstituted phenols (2-X-ArOH), related
      to the H-atom transfer (HAT) and single-electron transfer (SET) mechanisms. The
      solvent and substituent effects on the conformers, the BDEs, and the IEs were
      studied using four electron-donating (EDG) and five electron-withdrawing (EWG)
      groups, in seven different solvents. In both the EDG- and/or EWG-substituted
      species of the parent compounds, radicals, and/or cation radicals, the most
      stable conformer is varied, depending on the medium and the substitution. The EWG
      substituents increase IEs, resulting in a weaker antioxidant activity than the
      EDG ones; the effect appears stronger on the IEs than on BDEs. However, although
      the liquid-phase IEs, which are related to solution-phase oxidation potentials,
      decrease with the polarity and/or the hydrogen-bonding ability of the solvent,
      the opposite holds true for the BDEs, exhibiting a weaker effect. The gas-phase
      calculated IE for benzene is among the most accurate ones in the field, compared
      to the experiment, that for phenol being the most accurate. In addition,
      calculated IEs for the 2-X-ArOH are in close agreement with the very few existing
      experimental ones. It is shown that the oxidation potentials are (a) highly
      correlated with the gas-phase ones, and (b) strongly solvent dependent. The
      stabilization/destabilization of the cation radical (SPC) contribution, in all
      media, is the decisive factor in the DeltaIE calculation. The reasonable
      correlations found between the DeltaBDE and DeltaIE could account well for the
      assumption of the simultaneous action of both mechanisms in the 2-X-ArOH, in both
      the gas and the liquid phase. It seems, however, that the presence of a
      particular solvent by itself is not sufficient enough for the HAT to SET
      transition. The involvement of specific ED and/or EW groups in the 2-X-ArOH seems
      also necessary. It appears that our theoretical approach is not only generally
      applicable to the set of substituents important to antioxidant activity but also
      useful in (a) the rational design of phenolic antioxidants and (b) affording
      accurate BDE and IE parameter values related to both possible antioxidant
      mechanisms.

PMID- 16986851
TI  - High-level ab initio studies of hydrogen abstraction from prototype hydrocarbon
      systems.
AB  - Symmetric and nonsymmetric hydrogen abstraction reactions are studied using state
      of-the-art ab initio electronic structure methods. Second-order Moller-Plesset
      perturbation theory (MP2) and the coupled-cluster singles, doubles, and
      perturbative triples [CCSD(T)] methods with large correlation consistent basis
      sets (cc-pVXZ, where X = D,T,Q) are used in determining the transition-state
      geometries, activation barriers, and thermodynamic properties of several
      representative hydrogen abstraction reactions. The importance of basis set,
      electron correlation, and choice of zeroth-order reference wave function in the
      accurate prediction of activation barriers and reaction enthalpies are also
      investigated. The ethynyl radical (*CCH), which has a very high affinity for
      hydrogen atoms, is studied as a prototype hydrogen abstraction agent. Our high
      level quantum mechanical computations indicate that hydrogen abstraction using
      the ethynyl radical has an activation energy of less than 3 kcal mol(-1) for
      hydrogens bonded to an sp(2) or sp(3) carbon. These low activation barriers
      further corroborate previous studies suggesting that ethynyl-type radicals would
      make good tooltips for abstracting hydrogens from diamondoid surfaces during
      mechanosynthesis. Modeling the diamond C(111) surface with isobutane and treating
      the ethynyl radical as a tooltip, hydrogen abstraction in this reaction is
      predicted to be barrierless.

PMID- 16986852
TI  - Deprotonated cytosine anions: a theoretical prediction of photoelectron spectra.
AB  - Predictions on the photoelectron spectra of deprotonated cytosine anions
      (cytosinate, Cye(-)) have been made with ab initio electron propagator methods.
      Two imino-oxo forms are most stable, but four other isomers have energies within
      10 kcal/mol. The first vertical electron detachment energies (VEDEs) for the
      three most stable Cye(-) isomers are approximately 3.4 eV. Imino-oxy VEDEs are
      about 0.3 eV smaller. For each anion, the lowest VEDE corresponds to a pi Dyson
      orbital. The order of higher final states is changed when relaxation and
      correlation effects are considered. Considerable mixing between lone-pair and
      bonding lobes occurs in the sigma Dyson orbitals.

PMID- 16986853
TI  - Structure of the photodissociation products of CCl4, CBr4, and CI4 in solution
      studied by DFT and ab initio calculations.
AB  - Various molecular species that can be populated during the photoreaction of
      carbon tetrahalides CX(4) (X = Cl, Br, I) in the gas phase and in solution have
      been studied by ab initio and density functional theory (DFT) calculations.
      Geometries, energies, and vibrational frequencies of CX(4), CX(3), CX(2),
      C(2)X(6), C(2)X(5), C(2)X(4), X(2), and the isomer X(2)CX-X were calculated and
      transition states connecting these species were characterized. Spin-orbit DFT
      (SODFT) computations were also performed to include the relativistic effects,
      which cannot be neglected for Br and I atoms. The calculated potential energy
      surfaces satisfactorily describe the reactions of the photoexcited CX(4)
      molecules. In the gas phase, the initial C-X bond rupture in CX(4) is followed by
      secondary C-X breakage in the CX(3) radical, leading to CX(2) and 2X, and the
      formation of C(2)X(6) or C(2)X(4) through bimolecular recombination of the CX(3)
      or CX(2) radicals is favored thermodynamically. In solution, by contrast, the
      X(2)CX-X isomer is formed via X-X binding, and two CX(3) radicals recombine
      nongeminately to form C(2)X(6), which then dissociates into C(2)X(4) and X(2)
      through C(2)X(5). The Raman intensities and the vibrational frequencies, as well
      as the absorption spectra and oscillator strengths of the Br(2)CBr-Br isomer in
      the gas phase and in various solvents were computed and the calculated absorption
      and Raman spectra of the Br(2)CBr-Br isomer in various solutions are in good
      agreement with the experimental data. The natural population analysis indicates
      that the Br(2)CBr-Br isomer corresponds to the recently reported solvent
      stabilized solvated ion pair (CBr(3)(+)//Br(-))(solv) in the highly polar alcohol
      solvent. The singlet-triplet energy separations of the CX(2) radicals in the gas
      phase and in solution were evaluated with high level computational methods, and
      the optimized geometric parameters are in good agreement with the experimental
      results. The geometric and energetic differences between the singlet and triplet
      states were explained by the electronic properties of the CX(2) radicals.
      C(2)X(4), C(2)X(5), and C(2)X(6) (X = Br, I) in the gas phase and in solution
      were optimized at different computational levels, and the optimized geometric
      parameters of C(2)I(4) are in very good agreement with the experimental data.

PMID- 16986854
TI  - Reaction mechanism of uracil bromination by HBrO: a new way to generate the enol
      keto form of 5-bromouracil.
AB  - Knowledge on the uracil bromination reaction is helpful for understanding the
      origin of the mutagenicity of 5-bromouracil (BrU). To get more details about this
      reaction, we explore the corresponding reaction mechanism by theoretical method.
      A total of seven pathways were studied for this purpose. The diketo form of BrU
      is observed as the main product in these pathways, which agrees well with
      experimental results. The most energy-favorable reaction pathway is found to be
      that Br and OH attacked the opposite sides of uracil. The reaction intermediate
      reported in the experiment is predicted to be reasonably stable. In the following
      step, a dehydration process occurs between H11 and O13-H14 when there are no
      explicit H(2)O taking part. However, when there are explicit water molecules in
      the environment, explicit H(2)O will lower the reaction barrier in the formation
      of reaction intermediates and the final product BrU. A proton-transfer process
      from C5 to O10 is facilitated by explicit H(2)O, which results in enol-keto form
      intermediate of this modified base (defined as BrU*). These results indicate a
      new way to generate the enol-keto form of BrU.

PMID- 16986855
TI  - Resonance raman excitation profile of a ruthenium(II) complex of dipyrido[2,3
      a:3',2'-c]phenazine.
AB  - The lowest energy transition of [Ru(CN)(4)(ppb)](2-) (ppb = dipyrido[2,3-a:3',2'
      c]phenazine), a metal-to-ligand charge transfer, has been probed using resonance
      Raman spectroscopy with excitation wavelengths (488, 514, 530, and 568 nm)
      spanning the lowest energy absorption band centered at 522 nm. Wave packet
      modeling was used to simultaneously model this lowest energy absorption band and
      the cross sections of the resonance Raman bands at the series of excitation
      wavelengths across this absorption band. A fit to within +/-20% was obtained for
      the Raman cross sections, close to the experimental uncertainty which is
      typically 10-20%. Delta values of 0.1-0.4 were obtained for modes which were
      either localized on the ppb ligand (345-1599 cm(-1)) or the CN modes (2063 and
      2097 cm(-1)). DFT calculations reveal that the resonance Raman bands observed are
      due to modes delocalized over the entire ppb ligand.

PMID- 16986856
TI  - Effect of reagent rotation on isotopic branching in (He, HD+) collisions.
AB  - A three-dimensional time-dependent quantum mechanical wave packet approach is
      used to calculate reaction probability (P(R)) and integral reaction cross section
      (sigma(R)) values for both the channels of the reaction He + HD(+) (v = 1; j = 0,
      1, 2, 3) --> HeH(D)(+) + D(H), over a range of translational energy (E(trans)) on
      the McLaughlin-Thompson-Joseph-Sathyamurthy (MTJS) potential energy surface using
      centrifugal sudden approximation for nonzero total angular momentum (J) values.
      The reaction probability plots as a function of translational energy for
      different J values exhibit several oscillations, which are characteristic of the
      system. It is shown that HeH(+) is preferred over HeD(+) for large J values and
      that HeD(+) is preferred over HeH(+) for small J values for all the rotational
      (j) states studied. The integral reaction cross section for both the channels and
      therefore the isotopic branching ratio for the reaction depend strongly on j in
      contrast to the marginal dependence shown by earlier QCT calculations. The
      computed results are in overall agreement with the available experimental
      results.

PMID- 16986857
TI  - A new method for measuring the diffusion coefficient in a gas phase.
AB  - A new and fast method for measuring the diffusion coefficients of binary gas
      mixtures using ion mobility spectrometry (IMS) has been developed. In this
      method, the sample is injected as a short pulse into the flowing drift gas,
      forming a Gaussian concentration profile inside the drift region. This Gaussian
      cloud is irradiated with a fast moving swarm of electrons to create negative
      ions. The flash of electrons is so short that the negative ions do not move much
      during the exposure time. The ions then drift toward the detector, where they are
      collected. The collected ion signal pattern reflects the spatial distribution of
      the sample inside the cloud at the time of exposure. This is repeated in
      intervals of 300-400 ms to monitor the spatial spreading of the molecules in the
      drift region. Consecutive IMS spectra show the evolution of the cloud over time.
      The collected spectra are fit to Gaussian functions to extract diffusion
      coefficients. Using this method, the diffusion coefficient of O(2), CHCl(3), and
      C(2)H(2)Cl(2) were measured, and the results are in good agreement with the
      previously reported experimental data.

PMID- 16986858
TI  - DNA cleavage by UVA irradiation of NADH with dioxygen via radical chain
      processes.
AB  - Efficient DNA cleaving-activity is observed by UVA irradiation of an O(2)
      saturated aqueous solution of NADH (beta-nicotinamide adenine dinucleotide,
      reduced form). No DNA cleavage has been observed without NADH under otherwise the
      same experimental conditions. In the presence of NADH, energy transfer from the
      triplet excited state of NADH ((3)NADH*) to O(2) occurs to produce singlet oxygen
      ((1)O(2)) that is detected by the phosphorescence emission at 1270 nm. No
      quenching of (1)O(2) by NADH was observed as indicated by no change in the
      intensity of phosphorescence emission of (1)O(2) at 1270 nm in the presence of
      various concentrations of NADH. In addition to the energy transfer, photoinduced
      electron transfer from (3)NADH* to O(2) occurs to produce NADH(*+) and O(2)(*-),
      both of which was observed by ESR. The quantum yield of the photochemical
      oxidation of NADH with O(2) increases linearly with increasing concentration of
      NADH but decreases with increasing the light intensity absorbed by NADH. Such
      unusual dependence of the quantum yield on concentration of NADH and the light
      intensity absorbed by NADH indicates that the photochemical oxidation of NADH
      with O(2) proceeds via radical chain processes. The O(2)(*-) produced in the
      photoinduced electron transfer is in the protonation equilibrium with HO(2)(*),
      which acts as a chain carrier for the radical chain oxidation of NADH with O(2)
      to produce NAD(+) and H(2)O(2), leading to the DNA cleavage.

PMID- 16986863
TI  - Atomic and molecular parity nonconservation and sum frequency generation
      solutions to the ozma problem.
AB  - Two Ozma problems are defined. Parity nonconservation is necessary for their
      solutions. Both problems may be solved by beta decay or atomic optical activity.
      Atomic and molecular sum frequency generation is chosen, as it supplies rich
      methods of effecting "gedanken" solutions to the Ozma problems. A new method of
      measuring a parameter manifesting molecular parity violations is advanced.

PMID- 16986864
TI  - Peierls transitions in ionic organic charge-transfer crystals with spin and
      charge degrees of freedom.
AB  - The quasi-one-dimensional electronic structure of organic charge-transfer (CT)
      salts rationalizes Peierls transitions in mixed or segregated stacks of pi
      electron donors (D) and acceptors (A). A microscopic Peierls-Hubbard model, HCT,
      is presented for CT salts with mixed stacks (Drho+Arho-)n and ionicity rho > 0.7.
      Dimerization opens a Peierls gap that, due to electron correlation, is the
      singlet-triplet gap, EST. In contrast to spin-Peierls systems, such as Heisenberg
      spin chains with rho = 1 and TSP < 20 K, Peierls transitions in CT salts with rho
      < 1 occur at higher TP and involve both spin and charge degrees of freedom.
      Linear electron-phonon coupling and an adiabatic approximation for a harmonic
      lattice are used to model the dimerization amplitude deltaT for T < TP, the
      magnetic (spin) susceptibility chiT, and the relative infrared intensity of
      totally symmetric molecular modes. Exact thermodynamics of HCT for stacks up to N
      = 12 sites are applied to two CT salts with TP approximately 50 and 120 K whose
      magnetism and infrared have not been modeled previously and to CT salts with
      inaccessibly high TP > 350 K whose description has been difficult. Ionic CT salts
      are correlated Peierls systems with a degenerate ground state (GS) at T = 0 whose
      elementary excitations are spin solitons, while dimerized ion-radical stacks that
      support triplet-spin excitons have nondegenerate GS. In less ionic CT salts,
      modulation of HCT parameters on cooling or under pressure leads to Peierls and/or
      neutral-ionic transitions of the GS, without appreciable thermal population of
      excited states. Correlations change the gap equation that relates EST at T = 0 to
      TP compared to free electrons, and size convergence is fast in stacks with large
      delta0 and high TP.

PMID- 16986865
TI  - Condensed-phase relaxation of multilevel quantum systems. I. An exactly solvable
      model.
AB  - An analytically solvable model of multilevel condensed-phase quantum dynamics
      relevant to vibrational relaxation and electron transfer is presented. Exact
      solutions are derived for the reduced system density matrix dynamics of a
      degenerate N-level quantum system characterized by nearest-neighbor hopping and
      off-diagonal coupling (which is linear in the bath coordinates) to a harmonic
      oscillator bath. We demonstrate that for N> 2 the long-time steady-state system
      site occupation probabilities are not the same for all sites; that is, they are
      distributed in a non-Boltzmann manner, which depends on the initial conditions
      and the number of levels in the system. Although the system-bath Hamiltonian
      considered here is restricted in form, the availability of an exact solution
      enables us to study the model in all regions of an extensive parameter space.

PMID- 16986866
TI  - Condensed-phase relaxation of multilevel quantum systems. II. Comparison of path
      integral calculations and second-order relaxation theory for a nondegenerate
      three-level system.
AB  - An exactly solvable model of multisite condensed-phase vibrational relaxation was
      studied in Paper I (Peter, S.; Evans, D. G.; Coalson, R. D. J. Phys. Chem. B
      2006, 110, 18758.), where it was shown that long-time steady-state site
      populations of a degenerate N-level system are not equal (hence, they are non
      Boltzmann) and depend on the initial preparation of the system and the number of
      sites that it comprises. Here we consider a generalization of the model to the
      case of a nondegenerate three-level system coupled to a high-dimensional bath:
      such a model system has direct relevance to a large class of donor-bridge
      acceptor electron transfer processes. Because the quantum dynamics of this system
      cannot be computed analytically, we compare numerically exact path integral
      calculations to the predictions of second-order time-local relaxation theory. For
      modest system-bath coupling strengths, the two sets of results are in excellent
      agreement. They show that non-Boltzmann long-time steady-state site populations
      are obtained when the level splitting is small but nonzero, whereas at larger
      values of the system bias (asymmetry) these populations become Boltzmann
      distributed.

PMID- 16986867
TI  - Characterization of architecture signals in proteins.
AB  - A quantitative, property-based approach to protein sequence analysis is
      presented, grounded in Fourier analysis and signal-processing methodologies. The
      resulting tools are applied to four protein structure families. We demonstrate
      the existence of architecture-specific, large amplitude periodicities in amino
      acid properties encoded in the sequences of proteins. These signals, whose
      statistical significance we establish, occur at well-defined wavenumbers, but are
      expressed in different physical properties in the various proteins which fold to
      a common architecture. This result explains the long-known convergence of
      unrelated sequences to a common fold. It is further suggested that these results
      provide a physical basis for the experimental observation that unrelated
      sequences that adopt similar architectures fold with similar rates.

PMID- 16986868
TI  - A universal criterion of melting.
AB  - Melting is analyzed dynamically as a problem of localization at a liquid-solid
      interface. A Lindemann-like criterion of melting is derived in terms of
      particular vibrational amplitudes, which turn out to equal a universal quotient
      (about one-tenth) of the molecular spacing, at the interface. The near
      universality of the Lindemann ratio apparently arises owing to strongly
      overdamped dynamics near melting, and despite the anharmonic interactions being
      system-specific. A similar criterion is derived for structural displacements in
      the bulk of the solid, in particular the premelted layer; the criterion is no
      longer strictly universal, but still depends only on the harmonic properties of
      the solid. We further compute the dependence of the magnitude of the elemental
      molecular translations, in deeply supercooled fluids, on the temperature and the
      high frequency elastic constants. We show explicitly that the surface tension
      between distinct liquid states, near the glass transition of a supercooled
      liquid, is nearly evenly split between entropic and energetic contributions.

PMID- 16986869
TI  - Localized orbital corrections for the calculation of ionization potentials and
      electron affinities in density functional theory.
AB  - This paper describes the extension of a previously reported empirical localized
      orbital correction model to the correction of ionization potential energies (IP)
      and electron affinities (EA) for atoms and molecules of first and second row
      elements. The B3LYP localized orbital correction version of the model (B3LYP-LOC)
      uses 22 heuristically determined parameters that improve B3LYP DFT IP and EA
      energy calculations on the G2 data set of 134 molecules from a mean absolute
      deviation (MAD) from experiment of 0.137 to 0.039 eV. The method significantly
      reduces the number of outliers and overall MAD to error levels below that
      achieved with G2 wave function based theory; furthermore, the new model has zero
      additional computational cost beyond standard DFT calculations. Although the
      model is heuristic and is based on a multiple linear regression to experimental
      errors, each of the parameters is justified on physical grounds, and each
      provides insight into the fundamental limitations of DFT, most importantly the
      failure of current DFT methods to accurately account for nondynamical electron
      correlation.

PMID- 16986870
TI  - Cytochrome c552 mutants: structure and dynamics at the active site probed by
      multidimensional NMR and vibration echo spectroscopy.
AB  - Spectrally resolved infrared stimulated vibrational echo experiments are used to
      measure the vibrational dephasing of a CO ligand bound to the heme cofactor in
      two mutated forms of the cytochrome c552 from Hydrogenobacter thermophilus. The
      first mutant (Ht-M61A) is characterized by a single mutation of Met61 to an Ala
      (Ht-M61A), while the second variant is doubly modified to have Gln64 replaced by
      an Asn in addition to the M61A mutation (Ht-M61A/Q64N). Multidimensional NMR
      experiments determined that the geometry of residue 64 in the two mutants is
      consistent with a non-hydrogen-bonding and hydrogen-bonding interaction with the
      CO ligand for Ht-M61A and Ht-M61A/Q64N, respectively. The vibrational echo
      experiments reveal that the shortest time scale vibrational dephasing of the CO
      is faster in the Ht-M61A/Q64N mutant than that in Ht-M61A. Longer time scale
      dynamics, measured as spectral diffusion, are unchanged by the Q64N modification.
      Frequency-frequency correlation functions (FFCFs) of the CO are extracted from
      the vibrational echo data to confirm that the dynamical difference induced by the
      Q64N mutation is primarily an increase in the fast (hundreds of femtoseconds)
      frequency fluctuations, while the slower (tens of picoseconds) dynamics are
      nearly unaffected. We conclude that the faster dynamics in Ht-M61A/Q64N are due
      to the location of Asn64, which is a hydrogen bond donor, above the heme-bound
      CO. A similar difference in CO ligand dynamics has been observed in the
      comparison of the CO derivative of myoglobin (MbCO) and its H64V variant, which
      is caused by the difference in axial residue interactions with the CO ligand. The
      results suggest a general trend for rapid ligand vibrational dynamics in the
      presence of a hydrogen bond donor.

PMID- 16986871
TI  - Classical studies of H atom trapping on a graphite surface.
AB  - The trapping and sticking of H and D atoms on the graphite (0001) surface is
      examined over the energy range 0.1-0.9 eV. Total electronic energy calculations
      based on density functional theory are used to develop a potential energy surface
      that allows for the full three-dimensional motion of the incident atom and the
      reconstruction of the bonding carbon atom, which must pucker out of the surface
      to form a stable bond. Classical methods are used to compute trapping cross
      sections as a function of incident energy. The C-H bond, once formed, rapidly
      dissociates without a mechanism to dissipate its excess energy. However, a number
      of long-lived trapping resonances exist, and for impact parameters below 1 A or
      so, several percent of the incident H atoms can remain trapped for 1 ps or more.
      This long-time trapping probability increases significantly when additional
      lattice degrees of freedom are added to carry energy away from the C-H stretch.
      Trapping can also increase with an increasing collision impact parameter, as H
      vibrations parallel to the surface become excited, leaving less energy in the C-H
      stretch. The trapping cross section at 1 ps reaches a maximum of 0.2 A2 for an H
      atom energy of 0.3 eV. Assuming that any atoms remaining trapped after 1 ps fully
      relax and stick, we estimate a lower bound for the sticking probability of H and
      D to be 0.024 and 0.050, respectively, about an order of magnitude below the
      experimental values.

PMID- 16986872
TI  - Excitation energy transfer between closely spaced multichromophoric systems:
      effects of band mixing and intraband relaxation.
AB  - We theoretically analyze the excitation energy transfer between two closely
      spaced linear molecular J-aggregates, whose excited states are Frenkel excitons.
      The aggregate with the higher (lower) exciton band edge energy is considered as
      the donor (acceptor). The celebrated theory of Forster resonance energy transfer
      (FRET), which relates the transfer rate to the overlap integral of optical
      spectra, fails in this situation. We point out that, in addition to the well
      known fact that the point-dipole approximation breaks down (enabling energy
      transfer between optically forbidden states), also the perturbative treatment of
      the electronic interactions between donor and acceptor system, which underlies
      the Forster approach, in general loses its validity due to overlap of the exciton
      bands. We therefore propose a nonperturbative method, in which donor and acceptor
      bands are mixed and the energy transfer is described in terms of a phonon
      assisted energy relaxation process between the two new (renormalized) bands. The
      validity of the conventional perturbative approach is investigated by comparing
      to the nonperturbative one; in general, this validity improves for lower
      temperature and larger distances (weaker interactions) between the aggregates. We
      also demonstrate that the interference between intraband relaxation and energy
      transfer renders the proper definition of the transfer rate and its evaluation
      from experiment a complicated issue that involves the initial excitation
      condition. Our results suggest that the best way of determining this transfer
      rate between two J-aggregates is to measure the fluorescence kinetics of the
      acceptor J-band after resonant excitation of the donor J-band.

PMID- 16986873
TI  - Thermal-cycling-induced spectral diffusion and thermal barriers in anisole-doped
      cyclohexane, an unusual multiphase host-guest system.
AB  - The host-guest system of anisole incorporated into a cyclohexane matrix was
      investigated in a series of hole-burning experiments. This system is unusual in
      that cyclohexane can freeze into coexisting solid phases. The hole-burning
      experiments support the existence of two crystalline phases and one disordered
      phase. A second surprising characteristic of this system is that the quasi-line
      absorption features of the spectra appear inverted at low temperature because of
      unexpected dominance of fluorescence and phosphorescence.

PMID- 16986874
TI  - Structure of N-acetylproline amide in liquid water: experimentally measured and
      numerically simulated infrared and vibrational circular dichroism spectra.
AB  - A few experimental and theoretical studies on the molecular structure of N
      acetylproline amide (AP) in D2O solution have been reported recently. However,
      there is no consensus of the precise structure of AP in D2O because
      spectroscopically determined structures and a theoretically simulated one have
      been found to be different from one another. To determine its aqueous solution
      structure, IR and vibrational circular dichroism spectra of both L- and D-form AP
      solutions were measured. Molecular dynamics simulations with two different force
      fields and density functional theory calculations for the trans and cis rotamers
      of AP were performed to numerically simulate those spectra. Comparisons between
      experimentally measured and computationally simulated spectra directly suggest
      that the AP in water adopts a polyproline II-like conformation and that the force
      field parameter ff03 in the AMBER 8 suite of programs is more realistic and
      reliable in predicting molecular structure of AP in water than the ff99 in AMBER
      7.

PMID- 16986875
TI  - Modeling the effects of torsional disorder on the spectra of poly- and oligo-(p
      phenyleneethynylenes).
AB  - The absorption spectra of phenyleneethynylene oligomers show an unusual change in
      shape with oligomer length. The unusual aspects of the spectra arise from
      rotation of the phenylene rings about the long axis of the oligomer. In the
      ground electronic state, the barrier to this rotation is low and the spectra in
      room temperature come from an ensemble of different structures. In the excited
      electronic state, the barrier to rotation is substantially higher, giving rise to
      strong nonlinear electron-phonon coupling. A multidimensional semiempirical model
      that includes these effects is developed for the photophysics of
      phenyleneethynylene oligomers. The ground-state energy is modeled with a
      molecular mechanics expression, and the excitation energy is modeled with an
      exciton model. Intermediate Neglect of Differential Overlap/Singles Configuration
      Interaction (INDO/SCI) calculations verify the exciton model and provide initial
      estimates of the model parameters. These parameters generate the qualitative
      features seen in experimental spectra. Inclusion of entropy effects from the
      multiple torsional coordinates is essential. Refinement of the parameters yields
      quantitative agreement with experiment. This agreement shows that coupling to
      torsional motion is a major factor in the spectroscopy and photophysics of these
      conjugated polymers.

PMID- 16986876
TI  - Electron transfer driven by proton fluctuations in a hydrogen-bonded donor
      acceptor assembly.
AB  - The temperature-isotope dependence of proton-coupled electron transfer (PCET) for
      a noncovalent molecular dyad is reported. The system consists of an excited-state
      Zn(II) porphyrin that transfers an electron to a naphthalene diimide acceptor
      through an amidinium-carboxylate interface. Two different isotope effects are
      observed for variant temperature regimes. A reverse isotope effect (i.e., kH/kD <
      1) is observed as T approaches 120 K (kH/kD = 0.9, 120 K), whereas a normal
      isotope effect (i.e., kH/kD > 1) is recovered as the temperature is increased
      (kH/kD = 1.2, 300 K). The transition between these limits is smooth, with a
      crossover temperature of T approximately 160 K. These observations are in
      accordance with charge-transfer dynamics that are susceptible to bath-induced
      fluctuations in the proton coordinate.

PMID- 16986877
TI  - Bending dynamics of acetylene: new modes born in bifurcations of normal modes.
AB  - Semiclassical techniques are used to analyze highly excited pure bending
      vibrational dynamics from spectra of C2H2. An analytic bifurcation approach is
      developed, based on critical points of a classical version of the quantum fitting
      Hamiltonian. At high energy four new types of anharmonic modes are born in
      bifurcations of the normal modes: local, orthogonal, precessional, and counter
      rotator. Visual insight into their nature is obtained with the help of computer
      generated three-dimensional animations. The connection between the local mode and
      the acetylene-vinylidene isomerization "reaction mode" is considered.

PMID- 16986878
TI  - Theoretical characterization of the (H2O)21 cluster: application of an n-body
      decomposition procedure.
AB  - Two low-energy minima of (H2O)21 with very different H-bonding arrangements have
      been investigated with the B3LYP density functional and RIMP2 methods, as well as
      with the TIP4P, Dang-Chang, AMOEBA, and TTM2-F force fields. The AMOEBA and TTM2
      F model potentials give an energy ordering that agrees with the results of the
      electronic structure calculations, while the TIP4P and Dang-Chang models give the
      opposite ordering. Insight into the role of many-body polarization for
      establishing the relative stability of the two isomers is provided by an n-body
      decomposition of the energies calculated using the various theoretical methods.

PMID- 16986879
TI  - Nonlinear wave-packet interferometry and molecular state reconstruction in a
      vibrating and rotating diatomic molecule.
AB  - We formulate two-color nonlinear wave-packet interferometry (WPI) for application
      to a diatomic molecule in the gas phase and show that this form of heterodyne
      detected multidimensional electronic spectroscopy will permit the reconstruction
      of photoinduced rovibrational wave packets from experimental data. Using two
      phase-locked pulse pairs, each resonant with a different electronic transition,
      nonlinear WPI detects the quadrilinear interference contributions to the
      population of an excited electronic state. Combining measurements taken with
      different phase-locking angles isolates various quadrilinear interference terms.
      One such term gives the complex overlap between a propagated one-pulse target
      wave packet and a variable three-pulse reference wave packet. The two-dimensional
      interferogram in the time domain specifies the complex-valued overlap of the
      given target state with a collection of variable reference states. An inversion
      procedure based on singular-value decomposition enables reconstruction of the
      target wave packet from the interferogram without prior detailed characterization
      of the nuclear Hamiltonian under which the target propagates. With numerically
      calculated nonlinear WPI signals subject to Gaussian noise, we demonstrate the
      reconstruction of a rovibrational wave packet launched from the A state and
      propagated in the E state of Li2.

PMID- 16986880
TI  - Spatial delocalization in para-H2 clusters.
AB  - We applied the quantum path integral Monte Carlo method for the study of (para
      H)N (N = 5-33) clusters at T = 2 K, exploring static and dynamic order, which
      originates from the effects of zero-point energy, kinetic energy, and thermal
      fluctuations in quantum clusters. Information on dynamic structure was inferred
      from the asymptotic tails of the cage correlation function calculated from the
      centroid Monte Carlo trajectory. The centroid cage correlation function decays to
      zero for large clusters (N = 15-33), manifesting the interchange of molecules
      between different solvation shells, with statistically diminishing back
      interchange. Further evidence for the floppiness of para-hydrogen clusters
      emerges from the Monte Carlo evolution of the centroid of a tagged molecule,
      which exhibits significant changes in the list of its first and second solvation
      shells due to the interchange of molecules between these shells.

PMID- 16986881
TI  - Effect of temperature and chain length on the bimodal emission properties of
      single polyfluorene copolymer molecules.
AB  - Fluorescence emission spectra were recorded for isolated polymer chains of the
      polyfluorene copolymer, F8BT [poly(9,9-di-n-octylfluorene-alt-benzothiadiazole)],
      at 298 and 20 K for two molecular weights (chain lengths). For long-chain F8BT at
      298 K, the observed distribution of single-molecule emission maxima G(Emax) is
      bimodal, with peaks at approximately 2.35 eV ("blue") and approximately 2.25 eV
      ("red"). Previously, the red forms have been assigned to polymer chains that
      possess intrachain contacts, which lowers the local singlet exciton energy. At
      approximately 20 K, G(Emax) collapses into a single broad distribution centered
      at approximately 2.3 eV for long-chain F8BT. However, this distribution can be
      further divided into a high-energy edge that is dominated by the "blue" form,
      while the remainder of the distribution is composed of the "red" form. Low
      molecular-weight F8BT samples emit exclusively from the blue form, and no shift
      in peak maxima with low temperature was observed. A Franck-Condon analysis
      reveals a decrease in emitting state displacements between spectra measured at
      298 and 20 K, suggesting that temperature-induced structural displacements are
      responsible for the change in the bimodal emission.

PMID- 16986882
TI  - Vibronic coupling in the ground and excited states of oligoacene cations.
AB  - The vibrational coupling in the ground and excited states of positively charged
      naphthalene, anthracene, tetracene, and pentacene molecules is studied on the
      basis of a joint experimental and theoretical study of ionization spectra using
      high-resolution gas-phase photoelectron spectroscopy and first-principles
      correlated quantum-mechanical calculations. Our theoretical and experimental
      results reveal that, while the main contribution to relaxation energy in the
      ground state of oligoacene systems comes from high-energy vibrations, the excited
      state relaxation energies show a significant redistribution toward lower
      frequency vibrations. A direct correlation is found between the nature of the
      vibronic interaction and the pattern of the electronic state structure.

PMID- 16986883
TI  - Electronic signatures of large amplitude motions: dipole moments of vibrationally
      excited local-bend and local-stretch states of S0 acetylene.
AB  - A one-dimensional local bend model is used to describe the variation of
      electronic properties of acetylene in vibrational levels that embody large
      amplitude local motions on the S0 potential energy surface. Calculations
      performed at the CCSD(T) and MR-AQCC levels of theory predict an approximately
      linear dependence of the dipole moment on the number of quanta in either the
      local bending or local stretching excitation. In the local mode limit, one
      quantum of stretching excitation in one CH bond leads to an increase of 0.025 D
      in the dipole moment, and one quantum of bending vibration in the CCH angle leads
      to an increase of 0.068 D. The use of a one-dimensional model for the local bend
      is justified by comparison to the well-established polyad model which reveals a
      decoupling of the large amplitude bending from other degrees of freedom in the
      range of Nbend = 14-22. We find that the same one-dimensional large amplitude
      bending motion emerges from two profoundly different representations, a one
      dimensional cut through an ab initio, seven-dimensional Hamiltonian and the three
      dimensional (l = 0) pure-bending experimentally parametrized spectroscopic
      Hamiltonian.

PMID- 16986884
TI  - Variational formula for the relaxation time in the Boltzmann equation.
AB  - The relaxation time approximation (RTA) is commonly employed in nonequilibrium
      statistical mechanics to approximate solutions to the Boltzmann equation in terms
      of an exponential relaxation to equilibrium. Despite its common use, the RTA
      suffers from the drawback that relaxation times commonly employed are independent
      of initial conditions. We derive a variational principle for solutions to the
      Boltzmann equation, which allows us to extend the standard RTA using relaxation
      times that depend on the initial distribution. Tests of the approach on a
      calculation of the mobility for a one-dimensional (1D) tight-binding band
      indicate that our analysis typically provides a better approximation than the
      standard RTA.

PMID- 16986885
TI  - Four-level optical line shape of a single molecule coupled to a single tunneling
      two-level system.
AB  - We propose a density-matrix theory for the four-level system consisting of a
      single optical two-level system (OTLS) coupled to a single two-level system
      tunneling along a vibrational coordinate (VTLS). Phonons induce jumping rates of
      the VTLS, but coherent tunneling has to be considered explicitly as well, because
      the Born-Oppenheimer potential of the tunnel variable may change upon optical
      excitation. The OTLS is subject to spontaneous emission and driven by a laser
      wave with arbitrary strength. Numerical simulations for various coupling cases
      reproduce limiting behaviors previously discussed separately in the literature,
      such as motional narrowing, cross transitions, optical saturation and pumping,
      and nonlinear effects. Our model also perfectly fits recent measurements of the
      spectra of a single molecule coupled to a single tunneling system in a disordered
      crystal.

PMID- 16986886
TI  - Vibrational spectral diffusion of azide in water.
AB  - Vibrational spectral diffusion denotes the time-dependent fluctuations of a
      solute's vibrational frequencies due to local environmental dynamics. Vibrational
      line shapes are weakly sensitive to spectral diffusion, whereas three-pulse
      vibrational echoes are much more sensitive. We report here on theoretical studies
      of spectral diffusion of the asymmetric stretch of the azide anion in heavy
      water. We run a classical molecular dynamics simulation of rigid azide in rigid
      water, and at every time step we calculate the azide's anharmonic asymmetric
      stretch frequency using an optimized quantum mechanics/molecular mechanics method
      developed earlier. This generates a frequency trajectory, which we use to
      calculate the absorption line shape and integrated three-pulse echo intensity.
      Our results for both the line width and the integrated echo intensity are in
      excellent agreement with experiment. Our calculated frequency time-correlation
      function is in excellent agreement with experiment for long times (greater than
      250 fs) but differs considerably from experiment at short times; our theoretical
      correlation function has a very pronounced oscillation, presumably due to
      intermolecular azide-water hydrogen-bond stretching dynamics.

PMID- 16986887
TI  - Single-molecule nanoprobes explore defects in spin-grown crystals.
AB  - Thin, platelike single crystals of p-terphenyl (PT) doped with terrylene impurity
      molecules can be prepared by spin-coating from solution. Strikingly, individual
      terrylene molecules can be observed traveling inside the crystal over distances
      of several micrometers by using single-molecule fluorescence imaging at room
      temperature. Analysis of the motion by single-particle tracking and correlation
      methods indicates that the molecules act as nanoprobes by exploring long, thin
      crack-like defects with correlated orientations, defects that can be difficult to
      observe by other means. Apparently, the regions accessible to the moving
      molecules are in the interior of the crystal and hence are partially protected
      from oxidation. In addition to the traveling molecules, which photobleach in
      times on the order of 32 s under continuous irradiation at 2 kW/cm2, two other
      spatially fixed populations are observed: one with transition dipole oriented
      along the c-axis of the crystal with a characteristic photobleaching time greater
      than 32 h, and one with a characteristic photobleaching time of 18 min.

PMID- 16986888
TI  - Transition event statistics in genetics and disordered kinetics. Theoretical
      approaches for extracting rate distributions from experimental data.
AB  - We study the analogies between the theory of rate processes in disordered systems
      and the overdispersed molecular clocks in evolutionary biology. A biological
      "molecular clock" expresses the statistics of the number of amino acid or
      nucleotide substitutions during evolution. Random variations of the evolution
      rates lead to statistical (overdispersed) molecular clocks which are described by
      random point processes with random substitution rates. We find that the models
      for overdispersed molecular clocks are equivalent to those of the random-rate or
      random channel models used in disordered kinetics. The number of transport
      (reaction) events in disordered kinetics plays the same role as the number of
      substitution events in molecular biology. We study the connections between the
      (observed) statistics of the transition events and the statistics of random rate
      coefficients and random channels; a unified approach is developed which is valid
      both in molecular biology and in disordered kinetics. We develop methods for
      extracting statistical information about the variations of rate coefficients from
      experimental or observed data regarding the fluctuations of the numbers of
      substitution, reaction, or transport events. For systems with static disorder,
      the observed statistics of the number of reaction events, expressed in terms of
      probabilities at a given time or by the cumulants of the number of transition
      events at a given time, contains the information necessary for evaluating the
      cumulants or the probability density of the rate coefficients or the density of
      states for random channel kinetics. For dynamic disorder this is not possible;
      further information about multitime probability distributions of the reaction
      events is needed.

PMID- 16986889
TI  - Evaluation of nonlinear quantum time correlation functions within the centroid
      dynamics formulation.
AB  - A method to evaluate nonlinear centroid correlation functions is presented that
      is amenable to simple numerical computation. It can be implemented with the
      centroid molecular dynamics method for approximate quantum dynamics with no
      additional assumptions. Two nonlinear correlation functions are evaluated for a
      model potential using this scheme and compared with results from exact quantum
      calculations.

PMID- 16986890
TI  - Sudden breakdown in linear response of a rotationally driven magnetic
      microparticle and application to physical and chemical microsensing.
AB  - In this work, sensing magnetic microparticles were used to probe both the local
      pH and the viscosity-dependent nonlinear rotational behavior of the particles.
      The latter resulted from a critical transition marking a driven particle's
      crossover from phase-locking to phase-slipping with an externally rotating
      magnetic field, i.e., a sudden breakdown in its linear response that can be used
      to measure a variety of physical quantities. The transition from simple rotation
      to wobbling is described both theoretically and experimentally. The ability to
      measure both chemical and physical properties of a system could enable
      simultaneous monitoring of chemical and physical interactions in biological or
      other complex fluid microsystems.

PMID- 16986891
TI  - Self-assembling cyclic peptides: molecular dynamics studies of dimers in polar
      and nonpolar solvents.
AB  - The self-assembly of cyclic D,L-alpha-peptides into hollow nanotubes is a crucial
      mechanistic step in their application as antibacterial and drug-delivery agents.
      To understand this process, molecular dynamics (MD) simulations were performed on
      dimers of cyclic peptides formed from cyclo [(-L-Trp-D-N-MeLeu-)4-]2 and cyclo [(
      L-Trp-D-Leu-)4-]2 subunits in nonpolar (nonane) and polar (water) solvent. The
      dimers were observed to be stable only in nonpolar solvent over the full 10 ns
      length of the MD trajectory. The behavior of the dimers in different solvents is
      rationalized in terms of the intersubunit hydrogen bonding, hydrogen bonding with
      the solvent, and planarity of the rings. It is shown that the phi and psi
      dihedral angles of a single uncapped ring in nonane lie in the beta-sheet region
      of the Ramachandran plot, and the ring stays in a flat conformation. Steered MD
      (SMD) simulations based on Jarzynski's equality were performed to obtain the
      potential of mean force as a function of the distance between the two rings of
      the capped dimer in nonane. It is also shown that a single peptide subunit
      prefers to reside close to the nonane/water interface rather than in bulk solvent
      because of the amphiphilic character of the peptide ring. The present MD results
      build the foundation for using MD simulations to study the mechanism of the
      formation of cyclic peptide nanotubes in lipid bilayers.

PMID- 16986892
TI  - The anharmonic vibrational potential and relaxation pathways of the amide I and
      II modes of N-methylacetamide.
AB  - We investigate the influence of isotopic substitution and solvation of N
      methylacetamide (NMA) on anharmonic vibrational coupling and vibrational
      relaxation of the amide I and amide II modes. Differences in the anharmonic
      potential of isotopic derivatives of NMA in D2O and DMSO-d6 are quantified by
      extraction of the anharmonic parameters and the transition dipole moment angles
      from cross-peaks in the two-dimensional infrared (2D-IR) spectra. To interpret
      the effects of isotopic substitution and solvent interaction on the anharmonic
      potential, density functional theory and potential energy distribution
      calculations are performed. It is shown that the origin of anharmonic variation
      arises from differing local mode contributions to the normal modes of the NMA
      isotopologues, particularly in amide II. The time domain manifestation of the
      coupling is the coherent exchange of excitation between amide modes seen as the
      quantum beats in femtosecond pump-probes. The biphasic behavior of population
      relaxation of the pump-probe and 2D-IR experiments can be understood by the rapid
      exchange of strongly coupled modes within the peptide backbone, followed by
      picosecond dissipation into weakly coupled modes of the bath.

PMID- 16986893
TI  - Role of rigidity on the activity of proteinase inhibitors and their peptide
      mimics.
AB  - The Bowman-Birk inhibitors (BBIs) are a family of proteins that share a canonical
      loop structure whose presence in a conserved conformation is linked to their
      inhibitory activity. We study the conformational properties of the canonical loop
      using a graph theoretical approach as implemented in the floppy inclusions and
      rigid substructure topography (FIRST). We find that the canonical loop is an
      independent rigid cluster in the natural inhibitors. We have further used this
      technique to identify residues that play an important role in the structural
      rigidity of the protein by quantifying their contribution to the overall rigidity
      of the inhibitor. We find that the conserved elements among the natural and
      synthetic peptides are the ones that contribute the most to rigidity, even if
      they are located far from the active site, as rigidity effects are nonlinear and
      hence nonlocal. The results help to elucidate why certain mutations in the loop
      of the BBI produce peptides that fail to have the designed inhibitory activity.

PMID- 16986894
TI  - Investigation of the excited state structure of DCM via ultrafast electronic
      pump/vibrational probe.
AB  - Time resolved visible pump, infrared probe transient absorption measurements of
      the solutes 4-dicyanomethylene-2-methyl-6-(p-(dimethylamino)styryl)-4H-pyran
      (DCM) and its isotopomer DCM-d6 are employed to probe the dynamics of charge
      transfer state formation in dimethyl sulfoxide (DMSO) and acetonitrile (MeCN). We
      observe a two stage charge transfer (CT): the first step is an instrument
      response-limited charge separation to the dicyanomethylene group, and the second
      involves a structural evolution of the dimethylamino group. Theoretical
      calculations and isotopic substitution indicate that the observed vibration is
      due to the dimethylamino group twisting out of plane, stabilizing the charge
      separation.

PMID- 16986895
TI  - Closed-form expressions of quantum electron transfer rate based on the stationary
      phase approximation.
AB  - Closed-form rate expressions are derived on the basis of the stationary-phase
      approximation for the Fermi golden rule expression of the quantum electron
      transfer (ET) rate. First, on the basis of approximate solutions of the
      stationary-phase points near DeltaG = 0, -lambda, and lambda, where DeltaG is the
      reaction free energy and lambda is the reorganization energy, three closed-form
      rate expressions are derived, which are respectively valid near each value of
      DeltaG. Numerical tests for a model Ohmic spectral density with an exponential
      cutoff demonstrate good performance of the derived expressions in the respective
      regions of their validity. In particular, the expression near DeltaG = -lambda,
      which differs from the semiclassical approximation only by a prefactor quadratic
      in DeltaG, works substantially better than the latter. Then, a unified formula is
      suggested, which interpolates the three approximate expressions and serves as a
      good approximation in all three regions. We have also demonstrated that the
      interpolation formula can serve as a good quantitative means for understanding
      the temperature dependence of the quantum ET rate.

PMID- 16986896
TI  - Mori-Zwanzig memory analysis in single-molecule spectroscopy.
AB  - We study the dynamical behavior of the Rhodospirillum molischianum LH2 complex
      based on intensity time series obtained from single-molecule spectroscopy
      experiments. This is achieved by reconstructing the memory function describing
      the time-dependent fluctuations of the excited states. We conclude that the
      apparent stochastic evolution of the dynamics is controlled by at least two
      different non-Markovian main processes.

PMID- 16986897
TI  - Testing for renewal and detailed balance violations in single-molecule blinking
      processes.
AB  - This paper examines methods to test one- and two-dimensional histograms for
      several features including the renewal properties, detailed balance violations,
      and experimental condition dependences. The tests are simple to implement and
      allow rigorous statistical determination of the existence of these kinetic
      features. The tests are used to determine the lower bound on the number of
      measurements necessary to differentiate underlying kinetic models.

PMID- 16986898
TI  - Hydrophobic aided replica exchange: an efficient algorithm for protein folding in
      explicit solvent.
AB  - A hydrophobic aided replica exchange method (HAREM) is introduced to accelerate
      the simulation of all-atom protein folding in explicit solvent. This method is
      based on exaggerating the hydrophobic effect of various protein amino acids in
      water by attenuating the protein-water attractive interactions (mimicking the
      Chaperon effect) while leaving other interactions among protein atoms and water
      molecules unchanged. The method is applied to a small representative protein, the
      alpha-helix 3K(I), and it is found that the HAREM method successfully folds the
      protein within 4 ns, while the regular replica exchange method does not fold the
      same protein within 5 ns, even with many more replicas.

PMID- 16986899
TI  - Lithium intercalation of phenyl-capped aniline dimers: a study by photoelectron
      spectroscopy and quantum chemical calculations.
AB  - Structural and electronic properties of pristine and lithium-intercalated, phenyl
      capped aniline dimers as a model for the lithium-polyaniline system have been
      studied by photoelectron spectroscopy and quantum chemical calculations. It was
      found that the electronic structure of reduced and oxidized forms of
      oligoanilines is only weakly affected by isomerism. Upon intercalation, charge
      transfer from the Li-atoms is remarkable and highly localized at N-atomic sites,
      where configurations are energetically favored in which both N atoms of the
      dimers are bound to Li atoms. Conversion of nitrogen sites is different for the
      two forms of aniline dimers and incomplete up to high intercalation levels,
      indicating a pronounced role of solid-state effects in the formation of such
      compounds.

PMID- 16986900
TI  - On the characterization of three-state conical intersections using a group
      homomorphism approach: the two-state degeneracy spaces.
AB  - Second-order degenerate perturbation theory, in conjunction with the group
      homomorphism method for describing a similarity transformation, are used to
      characterize the subspace of two-state conical intersections contained in the
      branching space of a three-state conical intersection. It is shown by explicit
      calculation, using the lowest three-state conical intersection of (CH)3N2, that a
      second-order treatment yields highly accurate absolute energies, even at
      significant distances from the reference point of three-state intersection. The
      excellent agreement between the second order and ab initio results depends on the
      average energy component, which is computed using 5 first-order terms and 15
      second-order terms. The second-order absolute energy change over the range rho =
      0.0-0.3 au, where rho is the distance from the three-state conical intersection
      in the branching space coordinates, is approximately 6500 and 9500 cm(-1) for the
      E(1=2) and E(2=3) seams, respectively, with the maximum ab initio energy
      deviation from degeneracy of 200 cm(-1) occurring at rho = 0.3 au. The
      characteristic parameters gIJ and hIJ are also predicted to great accuracy, even
      at large rho, with the error growing to only 10-15% at rho = 0.3 au.

PMID- 16986901
TI  - Correlations in single molecule photon statistics: renewal indicator.
AB  - Multiple time scales are the intrinsic nature of complex systems and can be
      revealed through single molecule photon statistical analysis. The standard
      Poisson indicator defined by the time-averaged initial condition measures photon
      bunching and antibunching but cannot be directly related to multiple time scales.
      A new indicator defined by the event-averaged initial condition is proposed to
      detect the deviation from the renewal behavior and to directly probe the effects
      of conformational fluctuations. Detailed calculations of modulated two-level
      systems are carried out using the transfer matrix method to demonstrate the
      difference between the two indicators. The relationship between ensemble-averaged
      survival probabilities and photon statistics is also explored in the context of
      single molecule measurements.

PMID- 16986902
TI  - Microscopic description of the low-temperature anomalies in silica and lithium
      silicate via computer simulations.
AB  - Information about the nature of the low-temperature anomalies and in particular
      the properties of the tunneling systems in silica and lithium silica glasses are
      revealed via computer simulations. The potential energy landscape of these
      systems is systematically explored for adjacent pairs of local minima which may
      act as double-well potentials (DWPs) at low temperatures. Three different types
      of DWPs are distinguished, related to perfectly coordinated silica, intrinsic
      silica defects, and extrinsic defects. Their properties such as the spatial
      extension and the dipole moment are characterized in detail. Furthermore, the
      absolute number of tunneling systems, that is, symmetric DWPs, is estimated. The
      results are compared with dielectric echo, specific heat, and acoustic
      experiments on Suprasil I and Suprasil W. A semiquantitative agreement for all
      relevant features is obtained.

PMID- 16986903
TI  - Photon counting statistics for blinking CdSe-ZnS quantum dots: a Levy walk
      process.
AB  - We analyze photon statistics of blinking CdSe-ZnS nanocrystals interacting with a
      continuous wave laser field, showing that the process is described by a ballistic
      Levy walk. In particular, we show that Mandel's Q parameter, describing the
      fluctuations of the photon counts, is increasing with time even in the limit of
      long time. This behavior is in agreement with the theory of Silbey and co-workers
      (Jung et al. Chem. Phys. 2002, 284, 181), and in contrast to all existing
      examples where Q approaches a constant, independent of time in the long time
      limit. We then analyze the distribution of the time averaged intensities, showing
      that they exhibit a nonergodic behavior, namely, the time averages remain random
      even in the limit of a long measurement time. In particular, the distribution of
      occupation times in the on-state compares favorably to a theory of weak
      ergodicity breaking of blinking nanocrystals. We show how our data analysis
      yields information on the amplitudes of power-law decaying on and off time
      distributions, information not available using standard data analysis of on and
      off time histograms. Photon statistics reveals fluctuations in the intensity of
      the bright state indicating that it is composed of several states. Photon
      statistics exhibits a Levy walk behavior also when an ensemble of 100 dots is
      investigated, indicating that the strange kinetics can be observed already at the
      level of small ensembles.

PMID- 16986904
TI  - On stochastic models of dynamic disorder.
AB  - In this paper we investigate some general aspects of stochastic models of dynamic
      disorder. First, we reexamine the Zwanzig model for the kinetics of escape
      through a fluctuating hole. We show that this model is trivially connected to the
      canonical model of the broadening of the zero-phonon line (ZPL) in crystals. This
      provides a new perspective of the Wang-Wolynes expression for the rate of escape
      from a geometric bottleneck with non-Markovian Gaussian fluctuations. Motivated
      by recent single-molecule experiments, we examine more general examples of
      fluctuation processes from the perspective of cumulant expansions. Finally, we
      discuss recent single-molecule experiments probing enzyme turnover performed by
      Xie and co-workers.

PMID- 16986905
TI  - Single molecule photon counting statistics for quantum mechanical chromophore
      dynamics.
AB  - We extend the generating function technique for calculation of single molecule
      photon emission statistics (Zheng, Y.; Brown, F. L. H. Phys. Rev. Lett. 2003, 90,
      238305) to systems governed by multi-level quantum dynamics. This opens up the
      possibility to study phenomena that are outside the realm of purely stochastic
      and mixed quantum-stochastic models. In particular, the present methodology
      allows for calculation of photon statistics that are spectrally resolved and
      subject to quantum coherence. Several model calculations illustrate the
      generality of the technique and highlight quantitative and qualitative
      differences between quantum mechanical models and related stochastic
      approximations when they arise. Calculations suggest that studying photon
      statistics as a function of photon frequency has the potential to reveal more
      about system dynamics than the usual broadband detection schemes.

PMID- 16986906
TI  - Meldrum's acid-derived thione dienophile in a convergent and stereoselective
      synthesis of a tetracyclic quassinoid intermediate.
AB  - An advanced intermediate toward anti-cancer quassinoids has been synthesized
      using a quadruple diene-transmissive [4+2]-cycloaddition strategy. High
      convergence is achieved thanks to a regio- and stereoselective hetero-Diels-Alder
      reaction using a thione. The relative stereochemistry of the final Diels-Alder
      adduct was controlled by tethered substituents introduced via a highly syn- and
      gamma-selective vinylogous Mukaiyama aldol.

PMID- 16986907
TI  - Stereoselective synthesis of 2-dienyl-substituted pyrrolidines using an eta4
      dienetricarbonyliron complex as the stereodirecting element: Elaboration to the
      pyrrolizidine skeleton.
AB  - Primary amines react with keto-aldehyde functionality located in the side-chain
      of an eta4-dienetricarbonyliron complex to provide the corresponding pyrrolidines
      in excellent diastereoselectivity. Two of the pyrrolidine products, 1i and 1k,
      have been elaborated into pyrrolizidines using a 1,5-C-H insertion and radical
      cyclization strategy, respectively.

PMID- 16986908
TI  - Reactivity studies of 3,3-bis(trimethylsilyl)-2-methyl-1-propene in Lewis acid
      catalyzed allylation reactions.
AB  - Allylation reagents, which possess geminal bis-trimethylsilyl substitution, are
      readily prepared from E- or Z-alkenyl bromides. The reactivity of 3,3
      bis(trimethylsilyl)-2-methyl-1-propene (1) is described and predominantly
      provides ene reactions with aldehydes to give alcohol 2 in the presence of
      BF3.OEt2. Alternatively, Sakurai allylation reactions of 1 are observed by using
      stronger Lewis acids in methylene chloride to exclusively yield E-trisubstituted
      alkenylsilanes 3.

PMID- 16986909
TI  - Catechol: A minimal scaffold for non-peptide peptidomimetics of the i + 1 and i +
      2 positions of the beta-turn of somatostatin.
AB  - The design, synthesis, and evaluation of a series of catechol-based non-peptide
      peptidomimetics of the peptide hormone somatostatin have been achieved. These
      ligands comprise the simplest known non-peptide mimetics of the i + 1 and i + 2
      positions of the somatostatin beta-turn. Incorporation of an additional side
      chain to include the i position of the beta-turn induces a selective 9-fold
      affinity enhancement at the sst2 receptor.

PMID- 16986910
TI  - Catalytic asymmetric addition of carbon dioxide to propylene oxide with
      unprecedented enantioselectivity.
AB  - New chiral catalyst systems were developed for the reaction of carbon dioxide
      with propylene oxide (PO) at atmospheric pressure to generate enantiomerically
      enriched propylene carbonate (PC). The best selectivity was achieved with a
      Co(III)(salen)-trifluoroacetyl complex and
      bis(triphenylphosphoranylidene)ammonium fluoride (PPN+F-) as catalysts, affording
      PC in 40% yield and 83% ee (selectivity factor = 19). In addition, PC was
      prepared for the first time by kinetic resolution of PO with tetrabutylammonium
      methyl carbonate (TBAMC, nBu4N+ (-)OOCOMe). With TBAMC as "activated CO2", up to
      71% ee was obtained.

PMID- 16986911
TI  - CsF-promoted acetyl dance at the narrow rim of p-tert
      butyl[3.1.3.1]homooxacalixarene.
AB  - In the acetylation of an oxygenated calix[4]arene homologue in the presence of
      CsF as a base, relaxation of the reaction system to the equilibrium composition
      takes place through several intra- and intermolecular steps that can be easily
      controlled to obtain the various acetyl derivatives. The effect of different
      bases is also discussed.

PMID- 16986912
TI  - Conformational templation in a singly bridged calix[7]arene derivative induced by
      alkali metal cations.
AB  - The first examples of alkali metal cation conformational templation of a
      calix[7]arene derivative were found in the alkali salts of 1,4-calix[7]crown-4,
      which were obtained by its treatment with the corresponding alkali metal
      carbonates. Competitive experiments showed that potassium and rubidium cations
      give the most effective templation, with a slight preference for the former.
      Experimental results and Monte Carlo conformational searches indicated that the
      cation interacts with all O-atoms including those of the crown-4 bridge.

PMID- 16986913
TI  - Catalytic asymmetric methallylation of ketones with an (H8-BINOLate)Ti-based
      catalyst.
AB  - The first catalytic asymmetric methallylation of ketones is reported. The
      catalyst, which is generated from titanium tetraisopropoxide, H8-BINOL, 2
      propanol, and tetramethallylstannane, reacts with ketones in acetonitrile to
      afford tertiary homoallylic alcohols in fair to excellent yields (55-99%) and
      fair to high enantioselectivities (46-90%). Ozonolysis of the resulting products
      provides access to chiral beta-hydroxy ketones, which are not readily prepared
      from direct asymmetric aldol reaction of acetone with ketones.

PMID- 16986914
TI  - Highly efficient and reusable dendritic catalysts derived from N
      prolylsulfonamide for the asymmetric direct aldol reaction in water.
AB  - The direct aldol reactions catalyzed by chiral dendritic catalysts derived from N
      prolylsulfonamide gave the corresponding products in high isolated yields (up to
      99%) with excellent anti diastereoselectivities (up to >99:1) and
      enantioselectivities (up to >99% ee) in water. In addition, catalyst 1e may be
      recovered by precipitation and filtration and reused for at least five times
      without loss of catalytic activity.

PMID- 16986915
TI  - Synthesis and characterization of water-soluble and photostable L-DOPA
      dendrimers.
AB  - A small drug molecule, L-DOPA, was converted into well-defined dendritic
      macromolecules. Their monodisperse nature was shown by NMR, MALDI-TOF-MS, and
      PAGE. A third-generation L-Dopa dendrimer contained 30 L-Dopa residues, which
      made up its core, branches, and periphery. Individual L-Dopa moieties in the
      dendrimer were connected to one another via hydrolyzable diester linkages. These
      Dopa dendrimers showed a 20-fold increase in aqueous solubility and enhanced
      photostability in solutions over L-Dopa under identical conditions.

PMID- 16986916
TI  - Synthesis and photophysical properties of electron-rich perylenediimide-fullerene
      dyad.
AB  - An electron-rich perylenediimide-C60 dyad has been prepared to explore a new type
      of donor-acceptor system. Time-resolved absorption measurements in benzonitrile
      revealed unambiguous evidence for the formation of a charge-separated state
      consisting of perylene diimide radical cation and C60 radical anion via
      photoinduced electron transfer, showing a new class of artificial photosynthetic
      models in terms of charge separation.

PMID- 16986917
TI  - Unexpected stereorecognition in nitrilase-catalyzed hydrolysis of beta-hydroxy
      nitriles.
AB  - Biocatalytic enantioselective hydrolysis of beta-hydroxy nitriles to
      corresponding (S)-enriched beta-hydroxy carboxylic acids has been achieved for
      the first time by an isolated nitrilase bll6402 from Bradyrhizobium japonicum
      USDA110. This offers a new "green" approach to optically pure beta-hydroxy
      nitriles and beta-hydroxy carboxylic acids. The observed remote stereorecognition
      is surprising because this nitrilase shows no enantioselectivity for the
      hydrolysis of alpha-hydroxy nitriles such as mandelonitrile.

PMID- 16986918
TI  - Modulating the rate of a native ligation coupling between tripyrrole derivatives
      by using specific dsDNA sequences.
AB  - The intrinsic recognition code associated with dsDNA allows either accelerating
      or retarding of a native chemical ligation reaction between tripyrrole ligands.
      The rate changes most probably stem from the sequence-dependent characteristics
      of the dsDNA-ligand complexes.

PMID- 16986919
TI  - Pseudosymmetry in azabicyclo[2.1.1]hexanes. A stereoselective construction of the
      bicyclic core of peduncularine.
AB  - Intramolecular photocycloaddition of 41 or its equivalent leads to the formation
      of photoadduct 25. While retro-Mannich fragmentation of the "b" bond in 25 leads
      to the formation of 44 (via 43), with the incorrect relative stereochemistry for
      the synthesis of peduncularine 5, selective fragmentation of the "a" bond in 25
      leads to the formation of 42 (via 26) with the correct relative stereochemistry
      for the synthesis of 5.

PMID- 16986920
TI  - Highly diastereoselective preparation of anti-1,2-diols by catalytic addition of
      alkynylsilanes to alpha-silyloxyaldehydes.
AB  - The catalytic, diastereoselective coupling of alpha-silyloxy aldehydes and
      alkynylsilanes catalyzed by a nickel(0) N-heterocyclic carbene complex provides
      an effective entry to anti-1,2-diols. The scope of couplings and extent of
      diastereoselection are excellent across a range of substrates.

PMID- 16986921
TI  - Unusual fluorescent monomeric and dimeric dialkynyl dipyrromethene-borane
      complexes.
AB  - Novel monomeric and dimeric dialkynyl borondipyrromethene dyes (E-Bodipy) have
      been prepared in two different ways, providing systems in which the boron center
      is attached to either two similar or two dissimilar acetylenic units
      incorporating chromophores such as pyrene or anthracene. Both families exhibit
      interesting fluorescence and redox properties in which almost quantitative
      intramolecular energy transfer occurs.

PMID- 16986922
TI  - The 1H NMR method for the determination of the absolute configuration of 1,2,3
      prim,sec,sec-triols.
AB  - The absolute configuration of 1,2,3-prim,sec,sec-triols can be assigned by
      comparison of the 1H NMR spectra of the tris-(R)- and the tris-(S)-MPA ester
      derivatives. An experimental demonstration of this correlation with 24 triols of
      known absolute configuration and a protocol using two parameters
      Deltadelta(RS)(H3) and the difference between Deltadelta RS (H2) and Deltadelta
      RS (H3) = absolute value (Delta(Deltadelta RS))-for its application to the
      determination of the absolute configuration of other triols are presented.

PMID- 16986923
TI  - Przewalskin A: A new C23 terpenoid with a 6/6/7 carbon ring skeleton from Salvia
      przewalskii maxim.
AB  - Przewalskin A (1), a novel C23 terpenoid with a 6/6/7 carbon ring skeleton, was
      isolated from Salvia przewalskii. Its structure was determined by comprehensive
      1D NMR, 2D NMR, and MS spectroscopic analysis and subsequently confirmed by a
      single-crystal X-ray diffraction study of its PDC oxidation derivative (2).
      Compounds 1 and 2 showed modest anti-HIV-1 activity with EC50 = 41 and 89
      microg/mL, respectively.

PMID- 16986924
TI  - Exceptionally mild, high-yield synthesis of alpha-fluoro acrylates.
AB  - Novel achiral and chiral alkyl alpha-(1,3-benzothiazol-2-ylsulfonyl)-alpha
      fluoroacetates can be readily synthesized by metalation-fluorination of (1,3
      benzothiazol-2-ylsulfonyl)acetates. DBU-mediated condensations of these
      fluorinated synthons with aldehydes proceed in a facile manner at 0 degrees C or
      at room temperature giving high yields of alpha-fluoro acrylates. Ketones are
      unreactive under these conditions. The presence of fluorine renders the synthon
      substantially more reactive compared to the unfluorinated analogue. Reactivity of
      alpha-(1,3-benzothiazol-2-ylsulfonyl)-alpha-fluoroacetate and the Horner
      Wadsworth-Emmons reagent (EtO)2P(O)CHFCOOEt has also been compared.

PMID- 16986925
TI  - Catalytic enantioselective synthesis of adociacetylene B.
AB  - A catalytic enantioselective total synthesis of adociacetylene B (2) in five
      steps is reported. The efficiency of this synthesis was enabled by an asymmetric
      zinc alkynylation catalyzed by the proline-derived ligand (1).

PMID- 16986926
TI  - Efficient microwave-assisted tandem N- to S-acyl transfer and thioester exchange
      for the preparation of a glycosylated peptide thioester.
AB  - A peptide carrying a mercaptomethylated proline derivative at the C-terminus was
      prepared by solid-phase peptide synthesis (SPPS) and converted to the thioester
      of 3-mercaptopropionic acid (MPA) by aqueous MPA under microwave irradiation
      conditions. This post-SPPS thioesterification reaction was successfully applied
      to the synthesis of a glycopeptide thioester composed of 25 amino acid (AA)
      residues, which was then used for the preparation of a 61-AA glycopeptide by the
      thioester condensation method.

PMID- 16986927
TI  - Asymmetric synthesis of 3-hydroxy-pyrrolidines via tin-lithium exchange and
      cyclization.
AB  - We report a method for the synthesis of chiral pyrrolidines using tin-lithium
      exchange and cyclization reactions. The precursors are formed readily from simple
      starting materials and undergo tin-lithium exchange by treatment with n
      butyllithium. Subsequent intramolecular carbolithiation is stereoselective to
      give highly enantiomerically enriched pyrrolidines in excellent yields.

PMID- 16986928
TI  - Preparation of indoles from alpha-aminonitriles: A short synthesis of FGIN-1-27.
AB  - Alpha-Aminonitriles derived from 2-aminocinnamic acid esters and amides can be
      cyclized under basic conditions to furnish substituted indole-3-acetic acid
      derivatives in quantitative yield. The reaction provides a simple access to a
      class of biologically active compounds.

PMID- 16986929
TI  - Enantioselective formal total synthesis of the antitumor macrolide bryostatin 7.
AB  - A new enantioselective synthesis of Masamune's AB fragment (1) for bryostatin 7
      is described. Key steps in the new route include a Meerwein-Ponndorf-Verley
      reduction to set the O(7) stereocenter and an alkylative union between the
      dithiane 6 and iodide 5 to construct the C(9)-C(10) bond. Because we have
      previously published a synthesis of Masamune's C-ring phenyl sulfone 2, our new
      route to 1 constitutes a formal total synthesis of bryostatin 7; it also corrects
      the previously reported spectral data for 1 in CDCl3.

PMID- 16986930
TI  - Tetrahydrofuran lignans via tandem oxidative anionic-radical processes or
      reductive radical cyclizations.
AB  - Several tetrahydrofuran lignans have become important due to their diverse
      biological activities. We present initial studies on short syntheses of some of
      the simplest members of this natural product class. Galgravin and Veraguensin are
      obtained in only three or four steps from nitroalkenes and allylic alcohols via a
      new tandem anionic-radical process, and reductive radical cyclizations of beta
      nitro ethers derived from the same precursors are suitable to obtain Galgravin as
      well as Galbelgin and Ganschisandrin.

PMID- 16986931
TI  - Golden times for allenes: Gold-catalyzed cycloisomerization of beta
      hydroxyallenes to dihydropyrans.
AB  - The gold(I)-catalyzed 6-endo cycloisomerization of beta-hydroxyallenes provides a
      mild and efficient access to chiral functionalized dihydropyrans which were
      obtained at room temperature in good chemical yields with axis-to-center
      chirality transfer. The method was extended to the beta-aminoallene 12, which
      afforded tetrahydropyridine 13 in good yield as well.

PMID- 16986932
TI  - Gold-catalyzed tandem cycloisomerization-hydroalkoxylation of homopropargylic
      alcohols.
AB  - The tandem cycloisomerization-hydroalkoxylation of various homopropargylic
      alcohols in the presence of an alcohol and a dual catalyst system, consisting of
      a gold precatalyst and a Bronsted acid, provides an efficient route to
      tetrahydrofuranyl ethers under mild reaction conditions. The reaction can be
      carried out in various solvents, including alcohol, with both terminal and
      internal alkynes as the substrate.

PMID- 16986933
TI  - New aspects of catalytic intramolecular C-H amination: unexpected formation of a
      seven-membered ring in nitrogen-containing systems.
AB  - The first example of the formation of a seven-membered ring by way of
      intramolecular-catalyzed amination of saturated C-H bonds is reported (Du Bois
      reaction). The influence of various structural parameters was studied, and it was
      shown that the unexpected regioselectivity observed in nitrogen-containing
      systems could be rationalized by conformational factors. These results open the
      way to innovative strategies for the general synthesis of polyfunctionalized
      piperidines.

PMID- 16986934
TI  - Total synthesis and comparative analysis of orlistat, valilactone, and a
      transposed orlistat derivative: Inhibitors of fatty acid synthase.
AB  - Concise syntheses of orlistat (Xenical), a two-carbon transposed orlistat
      derivative, and valilactone are described that employ the tandem Mukaiyama aldol
      lactonization (TMAL) process as a key step. This process allows facile
      modification of the alpha-side chain. Versatile strategies for modifying the
      delta-side chain are described, involving cuprate addition and olefin metathesis.
      Comparative antagonistic activity of these derivatives toward a recombinant form
      of the thioesterase domain of fatty acid synthase is reported along with
      comparative activity-based profiling.

PMID- 16986935
TI  - 1-phenylprop-2-ynyl acetate: a useful building block for the stereoselective
      construction of polyhydroxylated chains.
AB  - (R)- or (S)-1-phenylprop-2-ynyl acetate was added stereoselectively to aldehydes
      to afford 4-hydroxy-1-phenylalk-2-ynyl acetates. The transformation of such
      adducts into the corresponding allylic 1,4-diacetates allowed a highly efficient
      transfer of chirality from C1 to C3 by a regio- and stereoselective [3,3]
      sigmatropic rearrangement. The obtained unsaturated 1,2-diacetates were useful
      synthetic intermediates whose double bond and/or phenyl group were transformed in
      different aldehydes, acids, or esters.

PMID- 16986936
TI  - Chemoselective formation of successive triazole linkages in one pot: "click
      click" chemistry.
AB  - A methodology for the successive regiospecific "clicking" together of three
      components in one pot via two triazole linkages is reported. The protocol
      utilizes copper(I)-mediated alkyne-azide cycloaddition reactions combined with a
      silver(I)-catalyzed TMS-alkyne deprotection under mild hydroalcoholic conditions.
      We exemplify the approach with peptide-based components to illustrate its
      compatibility with polyfunctionalized biomolecules. The method constitutes a
      promising tool for peptide ligation. We also provide a procedure for directly
      using TMS-alkynes as the cycloaddition partner in classical "click" chemistry.

PMID- 16986937
TI  - Asymmetric multicomponent reactions: diastereoselective synthesis of substituted
      pyrrolidines and prolines.
AB  - A novel diastereoselective synthesis of substituted pyrrolidines has been
      developed. Asymmetric multicomponent reactions of optically active
      phenyldihydrofuran, N-tosyl imino ester, and silane reagents in a one-pot
      operation afforded highly substituted pyrrolidine derivatives
      diastereoselectively. The reaction is quite efficient and constructed up to three
      stereogenic centers in a single operation.

PMID- 16986938
TI  - Heliespirones B and C: two new plant heliespiranes with a novel spiro
      heterocyclic sesquiterpene skeleton.
AB  - From the medium, polar bioactive fractions of leaf aqueous extract of Helianthus
      annuus L., heliespirones B (2) and C (3) have been isolated. The structural
      elucidation was based on extensive spectral studies. A probable biogenesis of
      heliespirone skeleton is proposed and discussed. The structure of heliespirone B
      has been confirmed by X-ray diffraction analysis.

PMID- 16986939
TI  - Novel and efficient synthesis of iminocoumarins via copper-catalyzed
      multicomponent reaction.
AB  - A variety of substituted iminocoumarins are prepared in good to excellent yields
      via a copper-catalyzed multicomponenet reaction of sulfonyl azides, terminal
      alkynes, and salicylaldehydes or o-hydroxylacetophenones. The method is general,
      mild, versatile, and efficient. A plausible mechanism for the domino process is
      proposed.

PMID- 16986940
TI  - New 4-spiroannulated tetrahydroisoquinolines by a one-pot sequential procedure.
      isolation and characterization of sigma-alkylpalladium heck intermediates.
AB  - A simple and efficient entry to new tetrahydroisoquinolines 4-spiroannulated to a
      five-membered heterocyclic ring has been achieved starting from secondary N
      allylamines and involving sequential 2-iodobenzylation/intramolecular Heck
      reaction/1,3-dipolar cycloaddition. A variety of Heck cyclization conditions were
      surveyed. When using Pd(PPh(3))(4) as catalyst, stable sigma-alkylpalladium
      iodide complexes were isolated and characterizated.

PMID- 16986941
TI  - Approaches to open fullerenes: a 1,2,3,4,5,6-hexaadduct of C60.
AB  - Complete saturation of a single six-membered ring on fullerene C60 has been
      achieved. The critical step in this first synthesis of a fully characterized
      1,2,3,4,5,6-hexaadduct consisted of a remarkable double 5-exo-trig addition of
      alkoxyl radicals promoted by lead tetraacetate. Two possible opening pathways ([2
      + 2 + 2] retrocycloadditions) for the newly synthesized compound were explored
      using quantum mechanical calculations. We found that the oxa bridges in the
      hexaadduct prevent ring opening through the retro[2 + 2 + 2] mechanism due to the
      high activation barrier and endothermicity of the reaction.

PMID- 16986942
TI  - Synthesis of 1,4-dithiins from pentathiepins.
AB  - Fused aromatic and heterocyclic 1,2,3,4,5-pentathiepins react with
      triphenylphosphine and alkynes bearing electron-withdrawing groups to give the
      corresponding 1,4-dithiins in high yields. Unsymmetrical alkynes add
      regioselectively to afford products in agreement with the electron distribution
      in a proposed reaction intermediate. A mechanism for these reactions is proposed.

PMID- 16986944
TI  - Novel crown ether and salen metal chelation driven molecular pincers.
AB  - The synthesis of novel metal chelation driven molecular pincers based on crown
      ether and salen ligand substructures are described. Their functionality was
      monitored by fluorescence spectroscopy using pyrene groups as fluorescence
      probes. The pincer was shown to function reversibly with respect to metal
      chelation with Zn2+ and also to chelate ditopically with 100 mol % of Zn2+ and
      100 mol % Li+ or 200 mol % of Li+ ion.

PMID- 16986943
TI  - Synthesis and circular dichroism spectroscopic investigations of oligomeric beta
      peptoids with alpha-chiral side chains.
AB  - Biomimetic oligomers are of large interest both as targets for combinatorial and
      parallel synthetic efforts and as foldamers. For example, shorter peptoid
      derivatives of beta-peptides, i.e., oligo-N-substituted beta-Ala, have been
      described as potential lead structures. Herein, we describe a solid-phase
      synthetic route to beta-peptoids with alpha-chiral aromatic N-substituents up to
      11 residues long. Furthermore, the folding propensities of these oligomers were
      investigated by circular dichroism (CD) spectroscopy.

PMID- 16986945
TI  - Practical total syntheses of epiquinamide enantiomers.
AB  - Short and practical syntheses of epiquinamide and its enantiomer were
      accomplished with high overall yields and high stereoselectivity from readily
      available starting materials.

PMID- 16986947
TI  - Synthesis of small carboranylsilane dendrons as scaffolds for multiple
      functionalizations.
AB  - Small carbosilane dendrons in which a closo-carborane is located at the focal
      point have been prepared by a sequence of steps involving hydrosilylation and
      reduction reactions. These compounds are used as scaffolds for peripheral
      functionalization with styrene, chlorovinylstyrene, or suitable carboranes, while
      keeping the C(cluster)-Si (C(c)-Si) bond. Modification of the core by reduction
      of the carborane with Mg/BrCH2CH2Br was also achieved.

PMID- 16986946
TI  - Stereoselective epoxidation of 4-deoxypentenosides: a polarized-pi model.
AB  - The high facioselectivity in the epoxidation of 4-deoxypentenosides (4-DPs) by
      dimethyldioxirane (DMDO) correlates with a stereoelectronic bias in the 4-DPs'
      ground-state conformations, as elucidated by polarized-pi frontier molecular
      orbital (PPFMO) analysis.

PMID- 16986948
TI  - Generation of allylic indium by hydroindation of 1,3-dienes and one-pot reaction
      with carbonyl compounds.
AB  - A hydroindation of 1,3-dienes by dichloroindium hydride (HInCl2) generates
      allylic indiums that react with carbonyl or imine moieties in a one-pot
      treatment. The former reaction proceeds in a radical manner, and the latter is
      ionic allylation. Moreover, both reactions require no additives such as radical
      initiators, Lewis acids, or transition metal catalysts.

PMID- 16986949
TI  - Modular asymmetric synthesis of 1,2-diols by single-pot allene
      diboration/hydroboration/cross-coupling.
AB  - Chiral allyl vinyl boronates are generated by catalytic enantioselective
      diboration of prochiral allenes. They may then be reacted, in situ, with a
      hydroborating reagent to form a novel triboron intermediate. The least hindered
      and most reactive C-B bond then participates in cross-coupling wherein the
      coupling is brought about by the same catalyst as that which catalyzed the
      diboration reaction. The remaining C-B bonds are then oxidized in the reaction
      workup, thereby allowing for the modular synthesis of chiral diols in a concise
      single-pot fashion.

PMID- 16986950
TI  - Expanding the scope of Mn(OAc)3-mediated cyclizations: synthesis of the
      tetracyclic core of tronocarpine.
AB  - Pyrroles, indoles, and surprisingly, indolines, when equipped with a pendant
      malonyl group on the nitrogen atom, were effective substrates in a Mn(III)
      mediated oxidative cyclization reaction, yielding the 1,2-annulated products in
      good to excellent yields. When indole acetonitrile was used as a substrate this
      method provided a rapid synthesis of a tetracyclic tronocarpine subunit.

PMID- 16986952
TI  - Rhodium-catalyzed asymmetric allylic substitution with boronic acid nucleophiles.
AB  - An enantio-, regio-, and diastereoselective rhodium(I)-catalyzed desymmetrization
      of a meso-cyclic allylic dicarbonate with organoboronic acid nucleophiles is
      described. The rhodium(I) catalyst formed in situ from [Rh(cod)OH]2 and Xyl-P
      PHOS allowed the S(N)2' allylic substitution product to be obtained with a range
      of arylboronic acids in enantiomeric excesses of up to 92% with
      regioselectivities of up to >20:1.

PMID- 16986951
TI  - N-oxides of adenosine-type nucleosides undergo pyrimidine ring opening and
      closure to give 5-amino-4-(1,2,4-oxadiazol-3-yl)imidazole derivatives.
AB  - Treatment of acylated adenosine N-oxides with carboxylic anhydrides and
      thiophenol resulted in pyrimidine ring opening followed by exocyclic ring
      closure. Ammonolysis gave 5-amino-4-(5-substituted-1,2,4-oxadiazol-3-yl)-1-(beta
      d-ribofuranosyl)imidazole derivatives, whereas iodine in methanol selectively
      unmasked the 5-amino group. Related flexible nucleoside analogues can be prepared
      from adenine-type precursors.

PMID- 16986953
TI  - Enantio- and diastereoselective hydrogenation via dynamic kinetic resolution by a
      cationic iridium complex in the synthesis of beta-hydroxy-alpha-amino acid
      esters.
AB  - Anti-selective asymmetric hydrogenation of alpha-amino-beta-keto esters via
      dynamic kinetic resolution under low hydrogen pressure has been achieved by an
      easily-handled cationic iridium complex with tetrakis[3,5
      bis(trifluoromethyl)phenyl]borate (BARF) as a counterion.

PMID- 16986954
TI  - Quassinoid support studies: fused carbocycle synthesis from benzoic acid
      derivatives via 5-hexynyl and 6-heptynyl radical cyclizations.
AB  - Eight bromoalkynes were prepared from substituted benzoic acids and treated with
      n-Bu3SnH to provide trans-fused perhydroindans or cis- and trans-fused
      perhydronaphthalenes. Atom-transfer reactions that accompany the free radical
      reactions resulted in several tandem radical cyclizations with formation of up to
      three carbon-carbon bonds in a single reaction. The relationship between these
      reactions and an approach to the quassinoid family of natural products is also
      described.

PMID- 16986955
TI  - Synthesis and PKC binding of a new class of a-ring diversifiable bryostatin
      analogues utilizing a double asymmetric hydrogenation and cross-coupling
      strategy.
AB  - The design, asymmetric synthesis, and biological evaluation of a new class of
      bryostatin analogues based on a pseudosymmetric spacer domain are described. An
      aryl bromide diversification site is incorporated allowing access to
      systematically varied analogues. The new analogues all exhibit potent, nanomolar
      affinity to PKC.

PMID- 16986956
TI  - Gold-catalyzed efficient formation of alkenyl enol esters/carbonates from
      trimethylsilylmethyl-substituted propargyl esters/carbonates.
AB  - A gold-catalyzed efficient method for the preparation of alkenyl enol
      esters/carbonates is developed. Besides the mild reaction conditions and high
      catalytic efficiency, the excellent E-selectivity of the nonenolic double bond is
      remarkable.

PMID- 16986957
TI  - Real-time monitoring of microwave-promoted Suzuki coupling reactions using in
      situ Raman spectroscopy.
AB  - The progress of microwave-promoted Suzuki reactions has been monitored using an
      in situ Raman spectroscopy apparatus assembled from commercially available
      components. It was possible to see if any reaction occurred and, if so, when it
      reached completion. In addition, the monitoring technique has given us an insight
      into the reaction, confirming that, when run in aqueous media, the coupling is in
      competition with the rapid deboronation of the boronic acid.

PMID- 16986958
TI  - Synthesis of a ketone analogue of biotin via the intramolecular Pauson-Khand
      reaction.
AB  - We report an improved synthesis of 5-(5-oxohexahydrocyclopenta[c]thiophen-1
      yl)pentanoic acid (ketone biotin, 1) based on the intramolecular Pauson-Khand
      cyclization. The synthesis proceeds in eight steps and in 2.7% overall yield from
      cyclohexene.

PMID- 16986959
TI  - Efficient and selective photogeneration of cholesterol-derived radicals by
      intramolecular hydrogen abstraction in model dyads.
AB  - Three model dyads have been synthesized by esterification of beta- and alpha
      cholesterol (Ch) with (S)- and/or (R)-ketoprofen (Kp). The alpha-dyads are
      efficient photogenerators of the 7-allyl Ch radicals by intramolecular H
      abstraction. Subsequent cyclization via C-C coupling occurs in a stereoselective
      way.

PMID- 16986960
TI  - Which is more likely in trichodiene biosynthesis: hydride or proton transfer?
AB  - The mechanisms proposed for enzyme-catalyzed formation of the sesquiterpene
      natural product trichodiene consistently include a step involving a 1,4-hydride
      transfer. Using quantum chemical methods (B3LYP/6-31+G(d,p) and mPW1PW91/6
      31+G(d,p)), we discovered two alternative pathways for transformation of the
      intermediate bisabolyl cation to the cuprenyl cation, one of which--a proton
      transfer pathway--appears to be much more energetically favorable (by more than
      10 kcal/mol) than the hydride transfer pathways usually proposed.

PMID- 16986961
TI  - First asymmetric total syntheses of (-)-subincanadines a and B, skeletally
      rearranged pentacyclic monoterpenoid indole alkaloids in aspidospermasubincanum.
AB  - We achieved the first asymmetric total syntheses of novel Aspidosperma indole
      alkaloids, (-)-subincanadines A and B, which involve an intramolecular
      diastereoselective Pictet-Spengler cyclization and an intramolecular Nozaki
      Hiyama-Kishi reaction as key steps in the total syntheses.

PMID- 16986962
TI  - Synthesis of macrosphelides with a thiazole side chain: new antitumor candidates
      having apoptosis-inducing property.
AB  - Hybrid compounds of macrosphelides and epothilones, both of which are natural
      macrolides having a 16-membered skeleton, were designed and synthesized using a
      ring-closing metathesis (RCM) strategy. Some of these hybrids were found to
      exhibit notable apoptosis-inducing activity against human lymphoma cells with
      higher potency than parent natural macrosphelides, and to be a promising lead
      compound for development of a new antitumor agent.

PMID- 16986963
TI  - Pd-Xantphos-catalyzed direct arylation of nucleosides.
AB  - Direct arylation of the exocyclic amino groups of nucleosides represents a simple
      approach to N-aryl nucleoside derivatives. To date, one limitation has been that
      only electron-deficient aryl bromides and triflates possessed adequate reactivity
      for efficient, direct N-arylation of nucleosides. We demonstrate herein that Pd
      Xantphos catalytic systems lead to successful N-arylation of suitably protected
      2'-deoxyadenosine and 2'-deoxyguanosine with a wide range of aryl bromides.

PMID- 16986964
TI  - Efficient C-N bond formations catalyzed by a proton-exchanged montmorillonite as
      a heterogeneous Bronsted acid.
AB  - Nucleophilic addition of sulfonamides and carboxamides to simple alkenes
      proceeded smoothly using a proton-exchanged montmorillonite catalyst. The spent
      catalyst was recovered easily from the reaction mixture and was reusable at least
      five times without any loss of activity. The unique acidity of the proton
      exchanged montmorillonite (H-mont) catalyst was found to be applicable to
      additional reactions: substitution of hydroxyl groups of alcohols with amides and
      anilines.

PMID- 16986965
TI  - Anion recognition by a silanediol-based receptor.
AB  - To explore the anion recognition ability of silanol hydroxy groups, a silanediol
      based receptor 1 was prepared. Spectroscopic studies and X-ray crystallography
      revealed that the receptor exhibits the characteristic recognition of anions via
      two hydrogen bonds in chloroform.

PMID- 16986966
TI  - A potential intermediate for the aza-Corey-Chaykovsky reaction: synthesis,
      structure, and thermolysis of a pentacoordinate 1,2-thiazetidine 1-oxide.
AB  - Thermolysis of a pentacoordinate 1lambda(6),2-thiazetidine, which was synthesized
      for the first time and characterized by X-ray crystallographic analysis, gave the
      corresponding aziridine and a cyclic sulfinate almost quantitatively. The
      potential intermediacy of a 1lambda(6),2-thiazetidine was suggested in the aza
      Corey-Chaykovsky reaction.

PMID- 16986967
TI  - Chiral boron enolate aldol additions to chiral aldehydes.
AB  - We have examined the double-diastereodifferentiating aldol addition reactions of
      chiral enolborinate 1a with chiral aldehydes leading to the corresponding aldol
      adducts with excellent levels of 1,5-anti diastereoselection.

PMID- 16986968
TI  - Asymmetric synthesis of fluorinated cyclic beta-amino acid derivatives through
      cross metathesis.
AB  - The asymmetric synthesis of several fluorinated cis-2-aminocycloalkane carboxylic
      acids (cis-2-ACACs) with a cross metathesis (CM) reaction as the key step has
      been carried out, constituting the first time a metathesis protocol has been
      undertaken with fluorinated imidoyl chlorides. Subsequent chemoselective
      hydrogenation of the olefin moiety, Dieckmann condensation, and stereoselective
      reduction of the iminic double bond afforded the corresponding beta-amino esters
      with several ring sizes. The asymmetric version of the process was achieved by
      using (-)-8-phenylmenthol as a chiral auxiliary.

PMID- 16986969
TI  - N-heterocyclic carbene catalyzed nucleophilic substitution reaction for
      construction of benzopyrones and benzofuranones.
AB  - N-Heterocyclic carbene as an efficient organic catalyst was employed to catalyze
      an intramolecular nucleophilic substitution reaction. When R(2) was a phenyl
      group, the cyclization process underwent isomerization, leading to generation of
      benzofuranone.

PMID- 16986970
TI  - Rhodium-catalyzed reaction of terminal alkynes with allylamine leading to (E)-3
      alkylidene N-heterocycles.
AB  - Terminal alkynes react with allylamine in the presence of a RhCl(PPh3)3 catalyst
      to give (E)-3-alkylidene-3,4-dihydro-2H-pyrroles. The products consist of two
      molecules of alkyne and one molecule of allylamine. Although dimers, trimers, and
      oligomers of alkynes are also obtained as byproducts, the addition of various
      ammonium salts to the reaction suppresses such oligomerization, resulting in an
      increase in product.

PMID- 16986971
TI  - Ring expansion/homologation--aldehyde condensation cascade using tert
      trihalomethylcarbinols.
AB  - Treatment of cyclic tert-trihalomethylcarbinols with CrCl(2) in THF/HMPA in the
      presence of aryl or aliphatic aldehydes initiates a cascade sequence of one
      carbon ring expansion-olefination affording conjugated exocyclic ketones. Acyclic
      tert-trihalomethylcarbinols undergo a comparable cascade of one carbon
      homologation-olefination.

PMID- 16986972
TI  - Stereoselective synthesis of 2,4,5-trisubstituted tetrahydropyrans using an
      intramolecular allylation strategy.
AB  - A highly stereoselective route to 2,4,5-trisubstituted tetrahydropyrans is
      reported. The key step employs an intramolecular allylation of a (Z)-allylsilane
      onto an aldehyde under Bronsted acid activation. Complete 1,4-stereoinduction
      accounts for the formation of only two out of the possible four THP products. The
      level of 1,3-stereoinduction is optimal when the reaction is carried out in an
      apolar solvent, which is in accord with electrostatics being key to controlling
      this aspect of the stereoselectivity.

PMID- 16986973
TI  - Polystyrene-supported hydroxyproline: an insoluble, recyclable organocatalyst for
      the asymmetric aldol reaction in water.
AB  - 4-Hhydroxyproline has been anchored to a polystyrene resin through click
      chemistry, and the resulting catalyst has been successfully applied to the direct
      aldol reaction in water. The high hydrophobicity of the resin and the presence of
      water are key to ensuring high stereoselectivity, whereas yield can be increased
      by using catalytic amounts of DiMePEG. This effect has been further demonstrated
      by the inefficiency of a homogeneous, more polar analogue.

PMID- 16986974
TI  - Nickel(0)-catalyzed asymmetric hydrocyanation of 1,3-dienes.
AB  - 1,2-Bis-diarylphosphinites are excellent ligands for the Ni(0)-catalyzed
      hydrocyanation of certain types of 1,3-dienes. 1-Phenyl-1,3-butadiene, 1-vinyl
      3,4-dihydronaphthalene, and 1-vinylindene undergo highly regioselective
      hydrocyanation under ambient conditions to give exclusively the 1,2-adducts in
      good to excellent yields. Using bis-1,2-diarylphosphinites derived from d
      glucose, the highest enantioselectivities to-date for asymmetric hydrocyanation
      of 1,3-dienes (70-83% ee's) have been obtained.

PMID- 16986975
TI  - Tandem Wittig rearrangement/aldol reactions for the synthesis of glycolate
      aldols.
AB  - A new tandem Wittig Rearrangement/aldol reaction of O-benzyl or O-allyl glycolate
      esters is described. This reaction generates two carbon-carbon bonds and two
      contiguous stereocenters in a single step from simple starting materials. The
      [1,2]-Wittig rearrangement proceeds under very mild reaction conditions that do
      not require the use of a strong base, and the 1,2-diol products are obtained in
      good yield with excellent diastereoselectivity (>20:1).

PMID- 16986976
TI  - Synthesis of the parent and substituted tetracyclic ABCD ring cores of
      camptothecins via 1-(3-aryl-2-propynyl)- 1,6-dihydro-6-oxo-2
      pyridinecarbonitriles.
AB  - A new synthetic pathway to the parent and substituted ABCD ring cores of the
      camptothecin family of alkaloids was developed. The N-alkylation of 1,6-dihydro-6
      oxo-2-pyridinecarbonitrile (2) with 3-bromo-1-phenylpropyne provided 3a using
      Curran's protocol. Treatment of 3a with a catalytic amount of DBU (5 mol %) at
      110 degrees C for 12 h produced indolizino[1,2-b]quinolin-9(11H)-one (6a), the
      parent ABCD ring core of camptothecin, in essentially quantitative yield.

PMID- 16986979
TI  - Brazil's Craniofacial Project: genetic evaluation and counseling in the Reference
      Network for Craniofacial Treatment.
AB  - OBJECTIVE: This study is part of Brazil's Craniofacial Project, which is the
      first initiative for a national characterization of craniofacial healthcare in
      Brazil. Our main aim was to describe the status of clinical genetics in the
      Brazilian Reference Network for Craniofacial Treatment. DESIGN: All services (n =
      29) listed in the Brazilian Reference Network for Craniofacial Treatment until
      October 2003 were contacted and invited to complete a questionnaire. Information
      regarding the general characteristics of the services, availability of genetic
      services, and genetic service providers was collected. RESULTS: The response rate
      was 86.2% (n = 25). Thirteen responding teams had clinical geneticists. Teams
      were predominantly located in the southeast region and affiliated with
      universities. Family interest in genetic counseling was reported by 95.7% (22/23)
      of the services. Although 80% of the responding services reported offering
      genetic counseling, only 45% (9/20) provided genetic counseling guided by
      clinical geneticists. CONCLUSION: Availability and access to genetic evaluation
      and counseling are still rudimentary in Brazil. Many services report family
      interest in genetic counseling, but there are few teams with clinical
      geneticists. Inclusion of this specialist on craniofacial teams is crucial to
      patient care. Development of standard guidelines for genetic evaluation of
      selected craniofacial anomalies and for local genetic counseling (e.g., for
      nonsyndromic cleft lip or palate) could be an alternative for improving current
      deficiencies in the system. Strengthening the degree of coordination and
      communication among craniofacial teams represents another important goal.

PMID- 16986980
TI  - A three-dimensional computed tomographic analysis of the cervical spine in
      unoperated infants with cleft lip and palate.
AB  - OBJECTIVE: To investigate anatomical variations and abnormalities of cervical
      spine morphology in unoperated infants with cleft lip and palate. DESIGN:
      Retrospective cross-sectional investigation of infants born with nonsyndromic
      cleft lip and palate using computed tomography scans acquired for investigation
      of a spectrum of clinical conditions. SETTING: Computed tomography scan data were
      obtained from 29 unoperated cleft lip and palate infants and 12 noncleft infants
      of Malay origin, ages 0 to 12 months. METHODS: Observational study of cervical
      spine computed tomography scans. Heights of cervical vertebral bodies (C2-C7) and
      intervertebral spaces were measured from landmarks identified from computed
      tomography reformats and three-dimensional computed tomography reconstructions.
      Linear modeling of heights and spaces, with age as a covariate, was undertaken to
      identify differences between the samples. RESULTS: Anomalous features observed in
      the cleft lip and palate sample included short posterior arch of C1 (2/29),
      abnormal development of the anterior arch of C1 (2/29), and fusions of the
      posterior arch of C2 and C3 (2/29). No anomalies of the cervical spine were
      observed in the noncleft sample. Although the heights of three cervical vertebral
      bodies were significantly smaller and two intervertebral spaces were
      significantly larger in infants with cleft lip and palate compared with noncleft
      infants (p < .05), overall length of the cervical spine did not differ
      significantly between the samples. CONCLUSION: There was evidence for subtle
      upper spinal anomalies in the infant cleft lip and palate population. Our finding
      of reduced size of some cervical vertebral bodies may reflect delayed upper
      spinal development in infants with cleft lip and palate.

PMID- 16986981
TI  - Distinctive cortical articulatory representation in cleft lip and palate: a
      preliminary functional magnetic resonance imaging study.
AB  - OBJECTIVE: To investigate cortical representation of articulation of the bilabial
      plosive in patients with cleft lip and palate. DESIGN: We examined cortical
      representation for /pa/-articulation in cleft lip and palate patients using blood
      oxygenation level-dependent functional magnetic resonance imaging. SUBJECTS: Data
      from four postsurgical adult cleft lip and palate patients were compared with
      those from six healthy volunteers. RESULTS: Activation foci were found in the
      bilateral primary sensorimotor cortex in all cleft lip and palate patients, as in
      the controls. The sensorimotor cortex ipsilateral to the side of cleft lip and
      palate showed greater activation in unilateral cleft lip and palate patients,
      whereas the sensorimotor cortex contralateral to the side on which cheiloplasty
      had been performed earlier showed greater activation in a bilateral cleft lip and
      palate patient. CONCLUSIONS: The results suggest that there may be an ipsilateral
      dominance in cortical representation during bilabial articulation to the side of
      the cleft in the upper lip.

PMID- 16986982
TI  - Hard palate repair timing and facial growth in cleft lip and palate: a systematic
      review.
AB  - OBJECTIVE: To evaluate the effect of timing of hard palate repair on facial
      growth in patients with cleft lip and palate, with special reference to cranial
      base, maxilla, mandible, jaw relation, and incisor relation. DESIGN: A systematic
      review. METHODS: The search strategy was based on the key words "facial growth,"
      "cleft lip palate," and "timing of (hard) palate repair." Case reports, case
      series, and studies with no control or comparison group in the sample were
      excluded. RESULTS: Fifteen studies met the selection criteria. All the studies
      were retrospective and nonrandomized. Five studies used cephalometry and casts,
      seven used cephalometry, and three used casts. Methodological deficiencies and
      heterogeneity of the studies prevented major conclusions. CONCLUSION: The review
      highlights the importance of further research. Prospective well-designed,
      controlled studies, especially targeting long-term results, are required to
      elucidate the effect of timing of hard palate repair on facial growth in patients
      with cleft lip and palate.

PMID- 16986983
TI  - Analysis of dental arch relationships in Swedish unilateral cleft lip and palate
      subjects: 20-year longitudinal consecutive series treated with delayed hard
      palate closure.
AB  - OBJECTIVE: To evaluate the dental arch relationships for a consecutive series
      from Goteborg, Sweden, who had delayed hard palate closure. DESIGN: Retrospective
      study. SETTING: Sahlgrenska University Hospital, Goteborg, Sweden. PATIENTS: The
      dental study models of 104 consecutive unilateral cleft lip and palate subjects.
      The study cohort was born between 1979 and 1994. Longitudinal records were
      available at ages 5 (n = 94), 10 (n = 97), 16 (n = 59), and 19 years (n = 46).
      Five assessors rated models according to the GOSLON Yardstick on two separate
      occasions each. INTERVENTIONS: These patients had been operated upon according to
      the Goteborg protocol of delayed hard palate closure (at age 8 years). RESULTS:
      85% of subjects were rated in groups 1 and 2 (excellent or very good outcome),
      12% were rated in group 3 (satisfactory), and 3% were assigned to group 4 (poor).
      No patients presented in Group 5 (very poor). Weighted kappa statistics for
      double determination of Yardstick allocation for five assessors demonstrated
      values between .65 and .90 for interrater agreement (good/very good) and between
      .70 and .90 for intrarater agreement (very good). CONCLUSIONS: Delayed hard
      palate closure as practiced in Goteborg since 1979 has produced the best GOSLON
      Yardstick ratings in a consecutive series of patients ever recorded worldwide,
      since the Yardstick was first used in 1983. However, it is noteworthy that a new
      protocol has been introduced in Goteborg since 1994, in which hard palate closure
      is done at 3 years due to concerns regarding speech.

PMID- 16986984
TI  - Complete unilateral cleft lip and palate: validity of the five-year index and the
      Goslon yardstick in predicting long-term dental arch relationships.
AB  - OBJECTIVE: To assess the validity of the 5-year index by subjecting study models
      at the age of 5 years to both the 5-year index and the Goslon yardstick, and then
      relating these results to the Goslon ratings at 10 years. DESIGN: Retrospective
      study. SETTING: Sahlgrenska University Hospital, Gothenburg, Sweden. PATIENTS:
      Study models of 94 patients with unilateral cleft lip and palate (UCLP) were
      evaluated at the ages of 5 and 10 years. The dental arch relationships were
      judged and categorized by using the Goslon yardstick for the 10-year models and
      both the Goslon yardstick and the 5-year index for the 5-year models. RESULTS:
      When used for 5- and 10-year models, the Goslon yardstick showed a kappa score of
      0.539 (weighted kappa = 0.579) with a moderate strength of agreement. However, 5
      year index scores at 5 years compared with the Goslon scores at 10 years showed a
      kappa score of only 0.043 (weighted kappa = 0.090), showing poor strength of
      agreement. Goslon scores at 10 years showed improvement in 14 cases when graded
      by the same Goslon yardstick at 5 years, whereas there was improvement in 23
      cases when the 5-year models were graded by the 5-year index (actual improvement
      in scores in UCLP cases is highly unlikely). CONCLUSIONS: Although use of the
      Goslon yardstick at 5 years has demonstrated some inherent flaws in its use at
      that age, these drawbacks are fewer than those when the 5-year index is used at 5
      years of age.

PMID- 16986985
TI  - Reliability of linear measurements on a virtual bilateral cleft lip and palate
      model.
AB  - OBJECTIVE: To assess the reliability and validity of measurements performed on
      three-dimensional virtual models of neonatal bilateral cleft lip and palate
      patients, compared with measurements performed on plaster cast models. MATERIALS
      AND METHODS: Ten high-quality plaster cast models of bilateral cleft lip and
      palate patients were scanned with an LDI-scanner to obtain a three-dimensional
      virtual model. Linear measurements were performed on the plaster cast models
      using a digital caliper and also on the three-dimensional virtual model using
      Viscam RP version 2.1 software. The measurements were performed by two observers
      on two occasions. RESULTS: Intraclass correlations ranging from .81 to .96 were
      found for all measurements except the measurement between the constructed
      reference point pr and reference point i (intraclass correlation = .40). A post
      hoc procedure in which top-view screen prints of the three-dimensional virtual
      model were used to perform the measurement between reference points pr and i
      demonstrated an intraclass coefficient of .90. CONCLUSIONS: Three-dimensional
      virtual models obtained by laser scanning neonatal cast models of bilateral cleft
      lip and palate patients can be used reliably and validly to perform linear
      measurements between existing reference points on the surface of the model using
      Viscam RP version 2.1 software. Measurements between reference points constructed
      outside the surface of the model cannot be validly performed on the three
      dimensional virtual model with the software used in this study. For these
      measurements, top-view screen prints of the three-dimensional virtual model can
      be used.

PMID- 16986986
TI  - Self-reports of psychosocial functioning among children and young adults with
      cleft lip and palate.
AB  - OBJECTIVE: A cross-sectional study was employed to determine the psychosocial
      effects of cleft lip and/or palate among children and young adults, compared with
      a control group of children and young adults without cleft lip and palate.
      PARTICIPANTS: The study comprised 160 children and young adults with cleft lip
      and/or palate and 113 children and young adults without cleft lip and/or palate.
      All participants were between 8 and 21 years of age. OUTCOME MEASURES:
      Psychological functioning (anxiety, self-esteem, depression, and behavioral
      problems) was assessed using validated psychological questionnaires. Happiness
      with facial appearance was rated using a visual analog scale. Social functioning,
      including experience of teasing/bullying and satisfaction with speech, was
      assessed using a semistructured interview. RESULTS: Participants with cleft lip
      and/or palate reported greater behavioral problems (p < .001) and more symptoms
      of depression (p < .01); they were teased more often (p < .001) and were less
      happy with their facial appearance (p < .01) and speech (p < .001), compared with
      controls. There were no significant difference between subjects with cleft lip
      and/or palate and subjects without cleft lip and/or palate in terms of anxiety (p
      > .05) or self-esteem (p > .05). Having been teased was a significant predictor
      of poor psychological functioning, more so than having a cleft lip and/or palate
      per se (p < .001). CONCLUSIONS: Teasing was greater among participants who had
      cleft lip and/ or palate and it was a significant predictor of poorer
      psychosocial functioning. Children and young adults with cleft lip and/or palate
      require psychological assessment, specifically focusing on their experience of
      teasing, as part of their routine cleft care.

PMID- 16986987
TI  - The hyoid bone in malay infants with cleft lip and palate.
AB  - OBJECTIVE: To compare morphological and positional variations of the hyoid bone
      in unoperated infants with cleft lip and palate (CL/P) with those in noncleft
      infants. DESIGN: Retrospective, cross sectional. PATIENTS AND METHODS: Three
      dimensional computed tomography scans were obtained from 29 unoperated CL/P
      infants of Malay origin aged between 0 and 12 months and from 12 noncleft infants
      in the same age range. Observations were made and measurements were obtained with
      a software package developed at the Australian Craniofacial Unit. The sizes of
      the hyoid bones and the position of the hyoid body and epiglottis in relation to
      the cervical spine were measured. Anatomical anomalies of the hyoid and
      prevalence of aspiration pneumonia were also documented. RESULTS: The hyoid bones
      and epiglottis were found to be located more inferiorly in CL/P infants compared
      with the noncleft infants. Also, 17% (5/29) of the CL/P infants had nonossified
      hyoid bodies. CONCLUSION: The results suggest that there are differences in the
      location and genesis of the hyoid bone in infants with CL/P that warrant further
      investigation.

PMID- 16986988
TI  - Goldenhar syndrome with various clinical manifestations.
AB  - Four case reports of children with clinical features of Goldenhar syndrome are
      described. Although the syndrome itself is not very rare, the occurrence in
      dizygotic twins and the presence of heart dextroposition and peripheral facial
      nerve palsy, which are rare associations, prompted the report of these cases.

PMID- 16986989
TI  - Dental age in children with a complete unilateral cleft lip and palate.
AB  - OBJECTIVE: To assess dental age in children with a complete unilateral cleft lip
      and palate and to compare this with a noncleft control group. DESIGN: Two-group,
      mixed-longitudinal cohort study. SETTING: Cleft group from an academic center for
      cleft lip and palate treatment. Noncleft control group from the same population.
      PATIENTS: Participants included 70 Caucasian children with a full complement of
      teeth and a complete unilateral cleft lip and palate (45 boys and 25 girls) from
      the Cleft Palate Craniofacial Center at the Radboud University Nijmegen Medical
      Center, Nijmegen, the Netherlands. The control group (90 boys and 91 girls) was
      taken from the Nijmegen Growth Study. MAIN OUTCOME MEASURE: Dental age was
      assessed on orthopantomograms. In the unilateral cleft lip and palate group,
      linear interpolation in individual age curves was applied to obtain the dental
      age at 5, 9.5, and 14 years of age. For these ages, a comparison was made with
      the noncleft control group. RESULTS: Boys and girls with a unilateral cleft lip
      and palate showed a significant delay in dental age, as compared with their
      noncleft peers at all three ages. This delay was more pronounced in boys than in
      girls. The gender effect was significant at chronological ages 5 and 14 years.
      CONCLUSIONS: Children with a complete unilateral cleft lip and palate have a
      delay in dental age, compared with noncleft children.

PMID- 16986990
TI  - Testing causal mechanisms of nonsyndromic craniosynostosis using path analysis of
      cranial contents in rabbits with uncorrected craniosynostosis.
AB  - OBJECTIVE: Various causal mechanisms of familial nonsyndromic craniosynostosis
      have been presented. One hypothesis suggests that overproduction of bone at the
      suture is the primary origin of craniosynostosis, which affects brain and cranial
      growth secondarily through altered intracranial pressure (Primary Suture Fusion
      Model). Other hypotheses suggest that decreased cranial base growth or abnormal
      brain growth are the primary cause of craniosynostosis (Cranial Base, Brain
      Parenchyma Models, respectively). This study was designed to investigate which
      model best describes neurocranial changes associated with craniosynostosis in a
      rabbit model through multivariate path analysis. DESIGN: Serial magnetic
      resonance imaging scans and intracranial pressure measurements were obtained at
      10, 25, and 42 days of age from 18 rabbits: six controls, six with delayed-onset
      synostosis, and six with early-onset synostosis. Five variables were collected
      from each rabbit: calvarial thickness at the affected suture, cranial base
      length, brain volume, cerebrospinal fluid volume, and intracranial pressure. This
      data set was used to test causal pathway relationships generated by the proposed
      models. Goodness of fit was measured by experimental group for each model.
      RESULTS: Primary Suture Fusion Model best explained the variables in both delayed
      onset and early-onset synostotic rabbits (Goodness of fit = 93%, 97%,
      respectively). Cranial Base Model (Goodness of fit = 94%) best explained the data
      in control rabbits. CONCLUSION: Results suggest that the primary site of
      craniosynostosis in craniosynostotic rabbits is most likely the synostosed
      suture. Other cranial vault anomalies are most likely secondary compensatory
      changes. Results of the present study may provide insight regarding the causal
      pathway of craniosynostosis.

PMID- 16986991
TI  - Velopharyngeal function during vocalization in infants.
AB  - OBJECTIVE: To determine the age at which infants achieve velopharyngeal closure
      during vocalization. DESIGN: Longitudinal with repeated measures. SETTING:
      Laboratory. PARTICIPANTS: Six healthy infants were studied monthly from ages 2 to
      6 months while they interacted with a parent and an investigator. MAIN OUTCOME
      MEASURES: The presence or absence of velopharyngeal closure, as determined by
      sensing ram pressure at the anterior nares. RESULTS: The velopharynx was open for
      windups, whimpers, and laughs, and it was closed for cries, screams, and
      raspberries, regardless of age. The frequency with which the velopharynx closed
      during syllable utterances increased significantly with age. CONCLUSIONS:
      Velopharyngeal closure for speech-like utterance increases with age, but is not
      complete and is still undergoing development at 6 months of age. Velopharyngeal
      closure during infancy may be influenced by pressure demands of the utterance;
      however, support for this speculation is stronger for other types of utterances
      than it is for speech-like utterances. The method used in this study holds
      promise for evaluating infants with suspected velopharyngeal impairment.

PMID- 16986992
TI  - Mothers' reflections on raising a child with a craniofacial anomaly.
AB  - OBJECTIVE: To conduct a qualitative evaluation of parenting among families with
      school-aged and young adolescent children with craniofacial anomalies (CFAs).
      METHODS: Interview responses were obtained from nine mothers of children ages 9
      to 14 years old with CFAs. Mothers were asked to describe their perceptions of
      their children, their children's special needs because of CFAs, and their
      parenting strategies. Narratives were coded into categories, including maternal
      concerns and worries, children's strengths, proactive maternal behaviors, and
      role of CFAs in the families' lives. RESULTS AND CONCLUSIONS: Mothers' responses
      indicated concern and protectiveness because of the challenges of having a CFA,
      as well as parenting strategies intended to promote autonomy and positive social
      and emotional adjustment.

PMID- 16986993
TI  - Hard palate repair timing and facial growth in unilateral cleft lip and palate: a
      longitudinal study.
AB  - OBJECTIVE: To investigate whether timing of hard palate repair had a significant
      effect on facial growth in patients with unilateral cleft lip and palate (UCLP).
      DESIGN: Retrospective longitudinal study. SETTING: Sri Lankan Cleft Lip and
      Palate Project. PATIENTS: A total of 104 patients with nonsyndromic UCLP who had
      hard palate repair by age 13 years, with their 290 cephalometric radiographs
      taken after lip and palate repair. MAIN OUTCOME MEASURES: Clinical notes were
      used to record surgical treatment histories. Cephalometry was used to determine
      facial morphology and growth rate. RESULTS: Timing of hard palate repair had a
      significant effect on the length and protrusion of the alveolar maxilla (PMP-A
      and SNA, respectively) and the anteroposterior alveolar jaw relation (ANB) at age
      20 years but not on their growth rates. CONCLUSION: Timing of hard palate repair
      significantly affects the growth of the maxilla in patients with UCLP. Late hard
      palate repair has a smaller adverse effect than does early hard palate repair on
      the growth of the maxilla. This timing effect primarily affects the
      anteroposterior development of the maxillary dentoalveolus and is attributed to
      the development being undisturbed before closure of the hard palate.

PMID- 16986994
TI  - Effects of a long-term volunteer surgical program in a developing country: the
      case in Vietnam from 1993 to 2003.
AB  - OBJECTIVE: This study evaluates the activities of the Japanese Cleft Palate
      Foundation from 1993 to 2003 in southern Vietnam. DESIGN: We assessed trends
      associated with patient age at first operation for primary lip repair and palate
      repair by using medical records of the patients. PARTICIPANTS: This study
      consisted of 790 patients with nonsyndromic cleft lip and/or palate (CL/P).
      RESULTS: The median patient age for lip repair was reduced from 14.0 years in
      1993 to 1.3 years by 2003. For palate repair, the median age was reduced from
      13.5 years in 1993 to 5.0 years in 1999 through 2003. The age distributions of
      both lip and palate repair in the later years became smaller than the age
      distributions in 1993. The number of adult patients declined throughout the
      period. CONCLUSIONS: The Japanese Cleft Palate Foundation contributed to lowering
      the age at first operation for CL/P and to reducing the number of adult patients
      in Ben Tre province, southern Vietnam. However, appropriate supports will be
      necessary to maintain CL/P treatment and to improve locally supported health care
      for patients with CL/P.

PMID- 16986995
TI  - An epidemiologic study of orofacial clefts with other birth defects in Victoria,
      Australia.
AB  - OBJECTIVE: To describe the epidemiological characteristics of oral clefts
      occurring with other birth defects in Victoria, Australia. METHODS: Information
      on infants and fetuses reported to the Victorian Birth Defects Register from 1983
      to 2000 was collected. Birth defects were classified as Pierre Robin Sequence,
      chromosomal anomaly, nonchromosomal syndrome, single-system defect, or multiple
      system defect. Pregnancy outcome and associations with selected infant and
      maternal features was examined. RESULTS: One third of the 2022 oral clefts
      recorded had other birth defects. There were more overall cleft cases involving
      multiple systems and chromosomal anomalies than any other birth defect group. The
      prevalence ratio of cleft lip with or without cleft palate (CL/P) was highest
      among multiple-system defects and chromosomal anomalies. Perinatal mortality was
      high, with termination of pregnancy highest in CL/P and chromosomal anomalies and
      multiple-system defects. There was a nonsignificant excess of clefts among
      multiple births. Women >or=40 years old had a tendency toward having a child with
      a cleft palate and another birth defect. There was an increased likelihood that
      women born in the U.K. would have a baby with CL/P and another birth defect.
      CONCLUSIONS: This is among the first reports in Victoria, Australia, describing
      oral clefts and other birth defects and associations between infant and maternal
      factors. Although some findings confirmed other population-based studies, some
      continued to be at variance. Nonetheless, the data derived support examination of
      babies diagnosed with clefts for associated comorbidities.

PMID- 16986996
TI  - Octyl-2-cyanoacrylate tissue glue (Dermabond) versus Monocryl 6 x 0 Sutures in
      lip closure.
AB  - OBJECTIVE: To assess the value of octyl-2-cyanoacrylate tissue glue in lip
      closure versus Monocryl stitches. DESIGN: Closure of a cleft lip can be done
      using transcutaneous Monocryl 6 x 0 sutures or using octyl-2-cyanoacrylate tissue
      glue (Dermabond). In 15 consecutive patients, the cleft lip was closed with
      Monocryl 6 x 0 and in another 15 consecutive patients, Dermabond was applied.
      Outcome parameters were complications, satisfaction of the parents with the
      cosmetic result, and the cosmetic result as judged by professionals. Satisfaction
      of the parents was assessed using a questionnaire and a visual analog scale. The
      cosmetic result as judged by professionals was measured by rating standardized
      pictures according to a visual analog scale. SETTING: A tertiary referral center
      for children with craniofacial anomalies. RESULTS: Complications were equal in
      both patient groups (p = .273). Satisfaction of the parents, as well as the
      professionals, with the cosmetic result did not show significant differences
      between the Monocryl 6 x 0 and the Dermabond groups (p = .922 and .983,
      respectively). However, parents were significantly more positive about the
      cosmetic result than the professionals were (p = .000). CONCLUSION: The results
      of lip closure using Dermabond tissue glue equal the cosmetic results of lip
      closure using transcutaneous Monocryl 6 x 0 sutures.

PMID- 16986997
TI  - Asian oral-facial cleft birth prevalence.
AB  - OBJECTIVE: To determine the clefting birth prevalence among Asian populations,
      specifically Chinese and Japanese, using raw counts from nonoverlapping published
      studies of Asian populations, and to investigate whether Asian clefting rates
      have been interpreted accurately as being up to twice the Caucasian rate. DESIGN:
      A literature review of articles giving raw counts of clefting in Asian
      populations, primarily Japanese and Chinese. MAIN OUTCOME MEASURES: Where
      possible, clefts were identified by the patients' ethnicity, country of origin,
      cleft type, syndromic status, and birth status. RESULTS: Prevalence rates of
      cleft lip with or without cleft palate per 1000 live births are reported.
      Syndromic plus nonsyndromic cleft lip with or without cleft palate: Chinese,
      1.30; Japanese, 1.34; Other Asian, 1.47; and total, 1.33. Nonsyndromic cleft lip
      with or without cleft palate: Chinese, 1.20; Japanese, 1.18; Other Asian, 1.22;
      and total, 1.19. CONCLUSIONS: Overall, Chinese and Japanese live birth prevalence
      rates for nonsyndromic cleft lip with or without cleft palate, based on the
      published reports of birth prevalence, are significantly lower than the oft
      quoted rate of 2 per 1000 for Asians. The apparent reason for the discrepancy is
      that many published prevalence rates included all pregnancies (live births plus
      pregnancy losses) and do not distinguish between syndromic and nonsyndromic
      clefts or between cleft palate alone and cleft lip with or without cleft palate.
      These results demonstrate that it is extremely important for current population
      based studies of clefts to include careful delineation of population groups,
      syndromes, cleft type, and birth status.

PMID- 16986998
TI  - Kinetics and mechanism of the sensitized photodegradation of uracil--modeling the
      fate of related herbicides in aqueous environments.
AB  - The dye-sensitized photodegradation of uracil (UR), the parent compound of
      several profusely employed herbicides, has been studied as a model of their
      environmental fate. In order to mimic conditions frequently found in nature,
      aqueous solutions of UR have been irradiated with visible light in the presence
      of the natural sensitizer riboflavin (Rf). The results indicate that UR is
      photostable in acid media, but is quickly degraded in pH 7 or pH 9 solutions,
      where singlet molecular oxygen [O2(1Delta(g))] and, to a lesser extent,
      superoxide radical anion (O2*-)-both species photogenerated from triplet excited
      Rf, 3Rf*-participate in the photodegradation. At pH 7, UR is slowly degraded
      through an O2*- -mediated mechanism, whereas Rf disappears through its reaction
      with O2(1Delta(g)) and, in the form of 3Rf*, with UR. On the contrary, at pH 9 Rf
      is photoprotected through two processes: its regeneration from the formed Rf
      radical species-a back electron transfer that also produces O2*- -and the
      elimination from the medium of O2(1Delta(g)) by its reaction with UR. The overall
      result of the preservation of ground state Rf is the continuity of the
      photosensitized process and, hence, of the UR degradation. Media with higher pH
      values could not be employed due to the fast photodegradation of Rf. With rose
      bengal (RB) as photosensitizer, the rate constants found for the overall
      interaction between UR and the photogenerated O2(1Delta(g)) were in the range 5 x
      10(5) M(-1) s(-1) (at pH 7) to 1.3 x 10(8) M(-1) s(-1) (in 1 M NaOH aqueous
      solution, mainly physical quenching). The maximum O2(1Delta(g)0-mediated
      photooxidation efficiencies with RB were reached at pH 11, where only the
      O2(1Delta(g)0-reactive quenching with UR was observed.

PMID- 16986999
TI  - The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox
      control.
AB  - The endoplasmic reticulum (ER) plays a major role in regulating synthesis,
      folding, and orderly transport of proteins. It is also essentially involved in
      various cellular signaling processes, primarily by its function as a dynamic
      Ca(2+) store. Compared to the cytosol, oxidizing conditions are found in the ER
      that allow oxidation of cysteine residues in nascent polypeptide chains to form
      intramolecular disulfide bonds. However, compounds and enzymes such as PDI that
      catalyze disulfide bonds become reduced and have to be reoxidized for further
      catalytic cycles. A number of enzymes, among them products of the ERO1 gene,
      appear to provide oxidizing equivalents, and oxygen appears to be the final
      oxidant in aerobic living organisms. Thus, protein oxidation in the ER is
      connected with generation of reactive oxygen species (ROS). Changes in the redox
      state and the presence of ROS also affect the Ca(2+) homeostasis by modulating
      the functionality of ER-based channels and buffering chaperones. In addition, a
      close relationship exists between oxidative stress and ER stress, which both may
      activate signaling events leading to a rebalance of folding capacity and folding
      demand or to cell death. Thus, redox homeostasis appears to be a prerequisite for
      proper functioning of the ER.

PMID- 16987000
TI  - Zinc coordination environments in proteins as redox sensors and signal
      transducers.
AB  - Zinc/cysteine coordination environments in proteins are redox-active. Oxidation
      of the sulfur ligands mobilizes zinc, while reduction of the oxidized ligands
      enhances zinc binding, providing redox control over the availability of zinc
      ions. Some zinc proteins are redox sensors, in which zinc release is coupled to
      conformational changes that control varied functions such as enzymatic activity,
      binding interactions, and molecular chaperone activity. Whereas the released zinc
      ion in redox sensors has no known function, the redox signal is transduced to
      specific and sensitive zinc signals in redox transducers. Released zinc can bind
      to sites on other proteins and modulate signal transduction, generation of
      metabolic energy, mitochondrial function, and gene expression. The paradigm of
      such redox transducers is the zinc protein metallothionein, which, together with
      its apoprotein, thionein, functions at a central node in cellular signaling by
      redistributing cellular zinc, presiding over the availability of zinc, and
      interconverting redox and zinc signals. In this regard, the transduction of
      nitric oxide (NO) signals into zinc signals by metallothionein has received
      particular attention. It appears that redox-inert zinc has been chosen to control
      some aspects of cellular thiol/disulfide redox metabolism. Tight control of zinc
      is essential for redox homeostasis because both increases and decreases of
      cellular zinc elicit oxidative stress. Depending on its availability, zinc can be
      cytoprotective as a pro-antioxidant or cytotoxic as a pro-oxidant. Any condition
      with acute or chronic oxidative stress is expected to perturb zinc homeostasis.

PMID- 16987001
TI  - NADPH oxidases: new regulators of old functions.

PMID- 16987002
TI  - Redox-dependent expression of cyclin D1 and cell proliferation by Nox1 in mouse
      lung epithelial cells.
AB  - NADPH oxidases produce reactive oxygen species (ROS) that serve as co-stimulatory
      signals for cell proliferation. In mouse lung epithelial cells that express Nox1,
      Nox2, Nox4, p22(phox), p47(phox), p67(phox), and Noxo1, overexpression of Nox1
      delayed cell cycle withdrawal by maintaining AP-1-dependent expression of cyclin
      D1 in low serum conditions. In cycling cells, the effects of Nox1 were dose
      dependent: levels of Nox1 that induced 3- to 10-fold increases in ROS promoted
      phosphorylation of ERK1/2 and expression of cyclin D1, whereas expression of Nox1
      with Noxo1 and Noxa1 (or expression of Nox4 alone) that induced substantial
      increases in intracellular ROS inhibited cyclin D1 and proliferation. Catalase
      reversed the effects of Nox1 on cyclin D1 and cell proliferation. Diphenylene
      iodonium, an inhibitor of NADPH oxidase activity, did not affect dosedependent
      responses of ERK1/2 or Akt to serum, but markedly inhibited the sequential
      expression of c-Fos and Fra-1 required for induction of cyclin D1 during cell
      cycle re-entry. These results indicate that Nox1 stimulates cell proliferation in
      actively cycling cells by reducing the requirement for growth factors to maintain
      expression of cyclin D1, whereas during cell cycle re-entry, NADPH oxidase
      activity is required for transcriptional activation of Fos family genes during
      the immediate early gene response.

PMID- 16987003
TI  - Mechanoregulation of monocyte chemoattractant protein-1 expression in rat
      vascular smooth muscle cells.
AB  - The authors have previously shown that arterial wall strain mediates the
      development of vessel wall inflammation in experimental hypertension. The current
      studies explore the mechanoregulation of monocyte chemoattractant protein-1 (MCP
      1), a potent pro-inflammatory chemokine, by mitogen-activated protein kinases
      (MAPK) and oxidative stress. Rat aortic smooth muscle (RASM) cells were subjected
      to cyclic strain on a uniform biaxial strain device. Strain rapidly activated
      both ERK1/2(MAPK) and p38(MAPK), with peak activation at 5 min. Strain induced a
      twofold increase in MCP-1 mRNA, which was attenuated by PD 98059, a specific
      ERK1/2(MAPK) inhibitor, and SB 203580, a specific p38(MAPK) inhibitor. Cyclic
      strain also increased production of superoxide anion via an NADPH oxidase
      dependent mechanism. To assess the potential role of reactive oxygen species in
      MAPK activation, cells were stretched in the presence of N-acetylcysteine, which
      had no effect on p38(MAPK) activation, but significantly inhibited ERK1/2(MAPK)
      activation and MCP-1 expression. In conclusion, redox-sensitive activation of
      ERK1/2(MAPK) and redox-insensitive activation of p38(MAPK) regulate straininduced
      MCP-1 expression in RASM cells. These findings define a role for MAPK signal
      transduction in establishing a pro-inflammatory state in the arterial wall, and
      thus implicate a potential molecular link between arterial wall strain and
      atherosclerosis.

PMID- 16987004
TI  - NOX2 and NOX4 mediate proliferative response in endothelial cells.
AB  - Increased levels of reactive oxygen species (ROS) contribute to many
      cardiovascular diseases. In neutrophils, ROS are generated by a NADPH oxidase
      containing p22phox and NOX2. NADPH oxidases are also major sources of vascular
      ROS. Whereas an active NOX2-containing enzyme has been described in endothelial
      cells, the contribution of recently identified NOX homologues to endothelial ROS
      production and proliferation has been controversial. The authors, therefore,
      compared the role of NOX2 with NOX4 and NOX1 in endothelial EaHy926 and human
      microvascular endothelial cells. NOX2 and NOX4 were abundantly expressed, whereas
      NOX1 expression was less prominent. NOX2, NOX4, and NOX1 were simultaneously
      present in a single cell in a perinuclear compartment. NOX2 and NOX4 co-localized
      with the endoplasmic reticulum (ER) marker calreticulin. Additionally, NOX2 co
      localized with F-actin at the plasma membrane. NOX2 and NOX4, which interacted
      with p22phox, as was shown by bimolecular fluorescent complementation,
      contributed equally to endothelial ROS production and proliferation, whereas NOX1
      depletion did not alter ROS levels under basal conditions. These data show that
      endothelial cells simultaneously express NOX2, NOX4, and NOX1. NOX2 and NOX4, but
      not NOX1, equally contributed to ROS generation and proliferation under basal
      conditions, indicating that a complex relation between NOX homologues controls
      endothelial function.

PMID- 16987005
TI  - NAD(P)H oxidase activity of Nox4 in chondrocytes is both inducible and involved
      in collagenase expression.
AB  - Reactive oxygen species (ROS) are regulators of redox-sensitive cell signaling
      pathways. In osteoarthritis, human interleukin-1beta is implicated in cartilage
      destruction through an ROS-dependent matrix metalloproteinase production. To
      determine the molecular source of ROS production in the human IL-1beta (hIL
      1beta)-sensitive chondrocyte immortalized cell line C-20/A4, transfected cells
      were constructed that overexpress NAD(P)H oxidases. First, RT-PCR analysis showed
      that the C-20/A4 cell line expressed Nox2, Nox4, p22( phox ), and p67( phox ),
      but not p47( phox ). It was found that ROS production by C-20/A4 chondrocytes
      does not depend on PMA and ionomycin activation. This indicates that Nox2 was not
      involved in the production of ROS. In C- 20/A4 cells that overexpress Nox4, hIL
      1beta stimulated ROS production three times more than the normal production of C
      20/A4 cells. Moreover, there was a fourfold increase in the production of
      collagenase (MMP-1) by chondrocytes that overexpress Nox4. Interestingly, MMP-1
      production in cells that overexpress Nox2 was not sensitive to hIL-1beta. These
      data suggest that under hIL-1beta stimulation, C-20/A4 chondrocytes produce MMP-1
      through a Nox4-mediated, ROS-dependent pathway.

PMID- 16987007
TI  - Single-cell optical imaging of the phagocyte NADPH oxidase.
AB  - The phagocyte NADPH oxidase is a key component of the innate immune response
      against invading microorganisms, because the generation of superoxide (O(2)(-))
      inside the phagocytic vacuole by this enzyme is responsible for microbial killing
      by mechanisms that are directly or indirectly dependent on reactive oxygen
      species (ROS) formation. Most of what is known about the membrane-embedded and
      cytosolic NADPH oxidase subunits and their intricate network of interactions on
      assembly and activation has been derived from biochemical and biophysical studies
      involving subcellular fractionation or reconstituted cell-free systems. Such
      investigations can be complemented by single-cell microscopy on phagocytes, which
      may reveal spatial and/or temporal details about NADPH oxidase assembly that
      cannot be obtained from fractionated-cell assays. In recent years, we have
      investigated the NADPH oxidase in neutrophils using two complementary optical
      imaging techniques: Raman microscopy, a vibrational spectroscopic technique that
      does not require protein labeling, and live-cell fluorescence microscopy, which
      sheds light on the dynamics of NADPH oxidase assembly in individual cells. Here,
      we briefly introduce these techniques, compare their characteristics, and show
      their potential for studying NADPH oxidase at the single-cell level. New
      microscopy data are presented to illustrate the versatility of Raman and
      fluorescence microscopy on intact neutrophils.

PMID- 16987006
TI  - Arachidonic acid-dependent activation of a p22(phox)-based NAD(P)H oxidase
      mediates angiotensin II-induced mesangial cell protein synthesis and fibronectin
      expression via Akt/PKB.
AB  - Angiotensin II (Ang II) induces protein synthesis and hypertrophy through
      arachidonic acid (AA)- and redoxdependent activation of the serine-threonine
      kinase Akt/PKB in mesangial cells (MCs). The role of NAD(P)H oxidase component
      p22( phox ) was explored in this signaling pathway and in Ang II-induced
      expression of the extracellular matrix protein fibronectin. Ang II causes
      activation of Akt/PKB and induces fibronectin protein expression, effects
      abrogated by phospholipase A(2) inhibition and mimicked by AA. Ang II and AAalso
      elicited an increase in fibronectin expression that was reduced with a dominant
      negative mutant of Akt/PKB. Exposure of the cells to hydrogen peroxide stimulates
      Akt/PKB activity and fibronectin synthesis. The antioxidant N-acetylcysteine
      abolished Ang II- and AA-induced Akt/PKB activation and fibronectin expression.
      Western blot analysis revealed high levels of p22( phox ) in MCs. Antisense (AS)
      but not sense oligonucleotides for p22( phox ) prevented ROS generation in
      response to Ang II and AA. AS p22( phox ) inhibited Ang II- or AA-induced Akt/PKB
      as well as protein synthesis and fibronectin expression. These data provide the
      first evidence, in MCs, of activation by AAof a p22( phox )-based NAD(P)H oxidase
      and subsequent generation of ROS. Moreover, this pathway mediates the effect of
      Ang II on Akt/PKB-induced protein synthesis and fibronectin expression.

PMID- 16987008
TI  - Regulation of novel superoxide-producing NAD(P)H oxidases.
AB  - Deliberate production of reactive oxygen species (ROS) are catalyzed by enzymes
      that belong to the NAD(P)H oxidase (Nox) family. The human genome contains seven
      members of the Nox family: the superoxide-producing enzymes Nox1 through Nox5 and
      the dual oxidases Duox1 and Duox2 that release hydrogen peroxide but not
      superoxide. Among them, the classical member gp91( phox )/Nox2 functions as the
      phagocyte NADPH oxidase, playing a crucial role in host defense. Although Nox2,
      heterodimerized with its membrane-spanning partner p22( phox ), is inactive in
      resting cells, during phagocytosis it forms an active complex with soluble
      regulatory proteins such as the organizer p47( phox ), the activator p67( phox ),
      and the small GTPase Rac. Here the authors describe how the novel superoxide
      producing Nox oxidases (Nox1, 3, 4, and 5) with different functions are regulated
      by p22( phox ), the Nox organizers, the Nox activators, and Rac, and how their
      expression is controlled at the transcriptional level.

PMID- 16987009
TI  - Regulation of the phagocyte NADPH oxidase by Rac GTPase.
AB  - Phagocytic leukocytes generate reactive oxygen species important for the killing
      of invading microorganisms. The source of these oxidants is the NADPH oxidase, a
      tightly controlled multicomponent enzyme made up of a membrane-associated
      catalytic moiety and cytosolic regulatory components that must assemble to form
      the active oxidase. The phagocyte NADPH oxidase was the first mammalian system
      shown to be directly regulated by a Rac GTPase. We review here our understanding
      of NADPH oxidase regulation by Rac, as well as the regulation of Rac itself, in
      phagocytic leukocytes. Rather than viewing Rac as a "cog" in the NADPH oxidase
      machinery, we argue for a view of Rac GTPases as critical "molecular switches"
      regulating the formation of ROS by phagocytic leukocytes under physiologic and
      pathologic conditions.

PMID- 16987010
TI  - Role of Nox family NADPH oxidases in host defense.
AB  - The phagocytic NADPH oxidase is recognized as a critical component of innate
      immunity, responsible for generation of microbicidal reactive oxygen species
      (ROS). This enzyme is one representative of the Nox family of oxidases (Nox1
      Nox5, Duox1, and Duox2) that exhibit diverse expression patterns and appear to
      serve a variety of functions related to ROS generation. Mounting evidence now
      suggests that several of these novel oxidases also serve in host defense,
      particularly those showing high expression along epithelial surfaces exposed to
      the external environment. Within these sites, Nox enzymes tend to be located on
      apical cell surfaces and release ROS into extracellular environments, where they
      can be used by known antimicrobial peroxidases. Moreover, microbial factors were
      shown in several cases to cause higher ROS production, either by direct oxidase
      activation or by inducing higher oxidase expression. Several oxidases are also
      induced by immune cytokines, including interferon-gamma, interleukin (IL)-4, and
      IL-13. Although most of the evidence supporting host defense roles for mammalian
      nonphagocytic oxidases remains circumstantial, recent evidence indicates that
      Drosophila Duox plays a role in host resistance to infection. Finally, oxidative
      defense against invading pathogens appears to be an ancient protective mechanism,
      because related oxidases are known to participate in disease resistance in
      plants.

PMID- 16987011
TI  - Physiology and pathophysiology of the DUOXes.
AB  - The dual oxidases (DUOXes) 1 and 2 are named based on their having both a domain
      homologous to the NADPH-oxidase of the phagocyte NADPH-oxidase gp91( phox )/NOX2
      and a domain homologous to thyroid peroxidase. The DUOX1 and DUOX2 mRNAs were
      originally cloned from thyroid tissue, and the corresponding proteins were
      recognized as intricate components of the thyroid hormone synthesis process,
      providing hydrogen peroxide essential for the organification of iodide. The
      function of DUOX2 in thyroid hormonogenesis has been firmly established by
      linking the congenital hypothyroid phenotype "total iodide organification defect"
      to biallelic inactivating DUOX2 mutations. Based on the expression of both DUOXes
      in combination with a peroxidase in a range of different tissues and functional
      studies; the concept evolves that DUOX is important not only for thyroid
      hormonogenesis but also as an integral part of the host defense system of mucosal
      surfaces, participates in the control of epithelial infection, augments surface B
      cell receptor signaling in lymphocytes, and is involved in generating a
      respiratory burst at fertilization.

PMID- 16987012
TI  - NADPH oxidases in the gastrointestinal tract: a potential role of Nox1 in innate
      immune response and carcinogenesis.
AB  - The gastrointestinal epithelium functions as physical and innate immune barriers
      against commensal or pathogenic microbes. NADPH oxidase 1 (Nox1) and dual oxidase
      2 (Duox2), highly expressed in the colon, are suggested to play a potential role
      in host defense. Guinea-pig gastric pit cells and human colonic epithelial cells
      (T84 cells) express Nox1. With regard to activation of Nox1, the gastric
      epithelial cells are primed with Helicobacter pylori lipopolysaccharide, whereas
      T84 cells preferentially use the Toll-like receptor (TLR) 5, rather than TLR4,
      against Salmonella enteritidis infection. Thus, gastric and colonic epithelial
      cells may use different TLR members to discern pathogenicities among bacteria,
      depending on their environments and to activate Nox1 appropriately for host
      defense. Nox1-derived reactive oxygen species (ROS) have been implicated in the
      pathogenesis of inflammation-associated tumor development. The human stomach does
      not express Nox1. Helicobacter pylori infection alone does not induce it, whereas
      Nox1 is specifically expressed in gastric adenocarcinomas. In the human colon,
      Nox1 is differentiation-dependently expressed, and its expression is upregulated
      in adenomas and well-differentiated adenocarcinomas. Although Nox1 expression may
      not be directly linked to mitogenic activity, Nox1-derived ROS may exert a cancer
      promoting effect by increasing resistance to programmed cell death of tumor
      cells.

PMID- 16987013
TI  - NADPH oxidases of the brain: distribution, regulation, and function.
AB  - The NADPH oxidase is a multi-subunit enzyme that catalyzes the reduction of
      molecular oxygen to form superoxide (O(2)(-)). While classically linked to the
      respiratory burst in neutrophils, recent evidence now shows that O(2)(-) (and
      associated reactive oxygen species, ROS) generated by NADPH oxidase in
      nonphagocytic cells serves myriad functions in health and disease. An entire new
      family of NADPH Oxidase (Nox) homologues has emerged, which vary widely in cell
      and tissue distribution, as well as in function and regulation. A major concept
      in redox signaling is that while NADPH oxidase-derived ROS are necessary for
      normal cellular function, excessive oxidative stress can contribute to
      pathological disease. This certainly is true in the central nervous system (CNS),
      where normal NADPH oxidase function appears to be required for processes such as
      neuronal signaling, memory, and central cardiovascular homeostasis, but
      overproduction of ROS contributes to neurotoxicity, neurodegeneration, and
      cardiovascular diseases. Despite implications of NADPH oxidase in normal and
      pathological CNS processes, still relatively little is known about the mechanisms
      involved. This paper summarizes the evidence for NADPH oxidase distribution,
      regulation, and function in the CNS, emphasizing the diversity of Nox isoforms
      and their new and emerging role in neuro-cardiovascular function. In addition,
      perspectives for future research and novel therapeutic targets are offered.

PMID- 16987014
TI  - NADPH oxidases in the kidney.
AB  - NADPH oxidases have a distinct cellular localization in the kidney. Reactive
      oxygen species (ROS) are produced in the kidney by fibroblasts, endothelial cells
      (EC), vascular smooth muscle cells (VSMC), mesangial cells (MCs), tubular cells,
      and podocyte cells. All components of the phagocytic NADPH oxidase, as well as
      the Nox-1 and -4, are expressed in the kidney, with a prominent expression in
      renal vessels, glomeruli, and podocytes, and cells of the thick ascending limb of
      the loop of Henle (TAL), macula densa, distal tubules, collecting ducts, and
      cortical interstitial fibroblasts. NADPH oxidase activity is upregulated by
      prolonged infusion of angiotensin II (Ang II) or a high salt diet. Since these
      are major factors underlying the development of hypertension, renal NADPH oxidase
      may have an important pathophysiological role. Indeed, recent studies with small
      interference RNAs (siRNAs) targeted to p22( phox ) implicate p22( phox ) in Ang
      II-induced activation of renal NADPH oxidase and the development of oxidative
      stress and hypertension, while studies with apocynin implicate activation of p47(
      phox ) in the development of nephropathy in a rat model of type 1 diabetes
      mellitus (DM). Experimental studies of the distribution, signaling, and function
      of NADPH oxidases in the kidney are described.

PMID- 16987015
TI  - Role of NADPH oxidases in disturbed flow- and BMP4- induced inflammation and
      atherosclerosis.
AB  - Atherosclerosis is an inflammatory disease, occurring preferentially in branched
      or curved arterial regions exposed to disturbed flow conditions including
      oscillatory shear stress (OS). In contrast, straight portions exposed to
      undisturbed laminar shear stress (LS) are relatively lesion free. The opposite
      effects of atheroprotective LS and proatherogenic OS are likely to be determined
      by differential expression of genes and proteins, including redox regulating
      factors. OS induces inflammation via mechanisms involving increased reactive
      oxygen species (ROS) production from the NADPH oxidases. Through a transcript
      profiling study and subsequent verification and functional studies, the authors
      discovered that OS induces inflammation by producing bone morphogenic protein 4
      (BMP4) in endothelial cells. BMP4 stimulates expression and activity of NADPH
      oxidase requiring p47phox and Nox-1 in an autocrine-like manner. The NADPH
      oxidase activation by BMP4 then leads to ROS production, NF-kappaB activation,
      intercellular adhesion molecule 1 (ICAM-1) expression, and subsequent increased
      monocyte adhesivity of endothelial cells. It is proposed that endothelial NADPH
      oxidases play a critical role in disturbed flow- and BMP4-dependent inflammation,
      which is the critical early atherogenic response occurring in atheroprone areas.
      This emerging field of shear stress, BMP4, NADPH oxidases, inflammation, and
      atherosclerosis is reviewed.

PMID- 16987016
TI  - Redox regulation of growth and death in cardiac myocytes.

PMID- 16987017
TI  - Acidosis regulates the stability, hydrophobicity, and activity of the BH3-only
      protein Bnip3.
AB  - Bnip3 is a prodeath member of the so-called BH3-only subfamily of Bcl-2 proteins.
      A major function of this class of proteins is to regulate the permeability state
      of the outer mitochondrial membrane by forming homoand hetero-oligomers inside
      the membrane. We reported previously that Bnip3 accumulates in cardiac myocytes
      during exposure to hypoxia, but coincident acidosis is required to activate the
      death program. Acidosis increased the rate of intracellular accumulation of Bnip3
      and promoted a tighter association with mitochondria. Here we report that acidic
      pH mediates increased half-lives of Bnip3 dimers and monomers (>3-) as well as
      that of a faster-migrating fragment (>10-) and confers protection against
      degradation by protease. Hydrophobic partitioning experiments revealed that Bnip3
      monomers and oligomers from hypoxia-acidic cell fractions associated
      significantly with the detergent layer, whereas protein from hypoxia-neutral
      myocytes did not. Acidosis promoted homodimerization of Bcl-xL but did not
      increase its association with detergent. Neutralization of the extracellular
      medium of cardiac myocyte cultures under hypoxia-acidosis resulted in rapid
      degradation of accumulated Bnip3 (half life, <2 h), coincident with cessation of
      the death program. Bnip3 monomers appear to be the active species because
      substitution of alanine for histidine at position 173 within the transmembrane
      (TM) domain prevented homodimerization but did not inhibit the death function.
      These results demonstrate a pH-sensitive shift in the stability and apparent
      hydrophobicity of Bnip3 monomers that correlates closely with membrane binding
      and function.

PMID- 16987018
TI  - Thioredoxin1 upregulates mitochondrial proteins related to oxidative
      phosphorylation and TCA cycle in the heart.
AB  - Thioredoxin1 (Trx1) inhibits hypertrophy and exhibits protective functions in the
      heart. To elucidate further the cardiac functions of Trx1, we used a DNA
      microarray analysis, with hearts from transgenic mice with cardiac- specific
      overexpression of Trx1 (Tg-Trx1, n = 4) and nontransgenic controls (n = 4).
      Expression of a large number of genes is regulated in Tg-Trx1, with a greater
      number of genes downregulated, versus upregulated, at high-fold changes. The
      peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1gamma)
      gene was among the top 50 significantly upregulated genes. By pathway analyses,
      we found that genes involved in both mitochondrial oxidative phosphorylation and
      the TCA cycle were upregulated in Tg-Trx1. We confirmed upregulation of
      cytochrome c oxidase (COX) components and mitochondrial transcription factor A in
      Tg-Trx1. The activity of citrate synthase and COX and the cardiac ATP content
      were significantly higher in Tg-Trx1. A transcription factor binding-site
      analysis showed that upregulated genes frequently contained binding sites for
      nuclear respiratory factor 1 (NRF1). Expression of NRF1 and PGC-1gamma was
      upregulated in Tg-Trx1, and Trx1 stimulated the transcriptional activity of NRF1
      and NRF2 in cardiac myocytes. These results suggest that, in cardiac myocytes,
      Trx1 upregulates mitochondrial proteins and enhances mitochondrial functions,
      possibly through PGC-1alpha and NRFs.

PMID- 16987019
TI  - A wave of reactive oxygen species (ROS)-induced ROS release in a sea of excitable
      mitochondria.
AB  - Once considered simply as the main source of ATP, mitochondria are now implicated
      in the control of many additional aspects of cell physiology, such as calcium
      signaling, and pathology, as in injury incurred on ischemia and subsequent
      reperfusion (I/R). Mitochondrial respiration is ordinarily accompanied by low
      level ROS production, but they can respond to elevated ROS concentrations by
      increasing their own ROS production, a phenomenon termed ROS-induced ROS release
      (RIRR). Two modes of RIRR have been described. In the first mode of RIRR,
      enhanced ROS leads to mitochondrial depolarization via activation of the MPTP,
      yielding a short-lived burst of ROS originating from the mitochondrial electron
      transport chain (ETC). The second mode of RIRR is MPTP independent but is
      regulated by the mitochondrial benzodiazepine receptor (mBzR). Increased ROS in
      the mitochondrion triggers opening of the inner mitochondrial membrane anion
      channel (IMAC), resulting in a brief increase in ETC-derived ROS. Both modes of
      RIRR have been shown to transmit localized mitochondrial perturbations throughout
      the cardiac cell in the form of oscillations or waves but are kinetically
      distinct and may involve different ROS that serve as second messengers. In this
      review, we discuss the mechanisms of these different modes of RIRR.

PMID- 16987020
TI  - Redox stress and the contributions of BH3-only proteins to infarction.
AB  - Ischemia followed by reperfusion is the primary cause of tissue injury and
      infarction during heart attack and stroke. The initiating stimulus is believed to
      involve reactive oxygen species that are produced during reperfusion when
      electron transport resumes in the mitochondria after suppression by ischemia.
      Programmed death has been shown to be a significant component of infarction, and
      evidence indicates that multiple pathways are initiated during both ischemia and
      reperfusion phases. Major infarction is preceded by severe ischemia that includes
      hypoxia, intracellular acidosis, glucose depletion, loss of ATP, and elevation of
      cytoplasmic calcium. The superimposition of a reactive oxygen surge on the latter
      condition provides the impetus for maximal damage. Compelling evidence implicates
      mitochondria not only as the source of initiating ROS but also as the focal
      sensors that translate the redox stress signal into a cellular-death response.
      Pivotal to this response are the BH3-only proteins that are activated by death
      signals and regulate mitochondrial communication with executioner proteins in the
      cytoplasm. The BH3-only proteins do this by controlling the activity of pores and
      channels in the outer mitochondrial membrane. To date at least six BH3-only
      proteins have been shown to contribute to ischemia-reperfusion death pathways in
      heart and/or brain; these include Bnip3, PUMA, Bid, Bad, HGTD-P, and Noxa. Here
      we review the evidence for these cell-death pathways and discuss their relevance
      to ischemic disease and infarction.

PMID- 16987021
TI  - Protein degradation by the 26S proteasome system in the normal and stressed
      myocardium.
AB  - The 26S proteasome is a multicatalytic threonine protease complex responsible for
      degradation of the majority of proteins in eukaryotic cells. In the last two
      decades, the ubiquitin proteasome system (UPS) has been increasingly recognized
      as an integral component in numerous biologic processes including cell
      proliferation, adaptation to stress, and cell death. The turnover of
      intracellular proteins inevitably affects the contributions of these molecules to
      cellular networks and pathways in any given tissue or organ, including the
      myocardium. Perturbations in the protein-degradation process have been shown to
      affect protein turnover and thereby affect the cardiac cell functions that these
      molecules are designated to carry out, engendering diseased cardiac phenotypes.
      Recent studies have implicated the role of proteasomes in stressed cardiac
      phenotypes including postischemia-reperfusion injury and cardiac remodeling
      (e.g., heart failure). The 26S proteasomes also appear to be susceptible to
      modulation by stresses (e.g., reactive oxygen species). This review focuses on
      roles of the 26S proteasome system in protein degradation; it provides an
      overview of the progress made in cardiac proteasome research as well as a
      discussion of recent controversies regarding the UPS system in diseased cardiac
      phenotypes.

PMID- 16987023
TI  - Zinc dynamics in the myocardial redox signaling network.
AB  - Zinc plays a vital role in various cellular functions. Zinc deprivation is
      associated with severe disorders related to growth, maturation, and stress
      responses. In the heart, zinc affects differentiation and regeneration of cardiac
      muscle, cardiac conductance, acute stress responses, and recovery of heart
      transplants. Recent discoveries of the molecular players in zinc homeostasis
      revealed that the amount of intracellular free zinc is tightly controlled on the
      level of uptake, intracellular sequestration, redistribution, storage, and
      elimination, consequently creating a narrow window of optimal zinc concentration
      in the cells. Most of intracellular zinc is bound to numerous structural and
      regulatory proteins, with metabolically active, labile zinc present in picoto
      nanomolar concentrations. The central position of zinc in the redox signaling
      network is built on its unique chemical nature. The redox inert zinc creates a
      redox active environment when it binds to a sulfur ligand. The reversible
      oxidation of the sulfur ligand is coupled to the reversible zinc release from the
      protein, thereby executing the task of so-called protein "redox zinc switch."
      Clearly, the impairment of zinc homeostasis will have far reaching physiological
      consequences.

PMID- 16987024
TI  - Thioredoxin-1 and posttranslational modifications.
AB  - Thioredoxin-1 is a 12 kDa protein that consists of a redox regulatory domain
      containing the active cysteine residues 32 and 35. These cysteines are conserved
      from bacteria to human. Unlike thioredoxins from lower species, mammalian
      thioredoxin-1 contains three additional nonactive cysteine residues at positions
      62, 69, and 73 (for human thioredoxin-1). Key biological functions of thioredoxin
      1 are antioxidative, anti-apoptotic, and pro-proliferative properties.
      Thioredoxin-1 is regulated by the ability of the thioredoxin reductase to reduce
      oxidized thioredoxin-1 at cysteines 32 and 35. However, posttranslational
      modifications of thioredoxin-1, including glutathionylation, thiol-oxidation, and
      S-nitros(yl)ation, at the nonactive cysteines importantly contribute to the
      regulation and functions of thioredoxin-1. This review focuses on the
      posttranslational modifications of the active and nonactive cysteines and their
      contribution for functional regulation of thioredoxin-1.

PMID- 16987022
TI  - S-nitrosylation: NO-related redox signaling to protect against oxidative stress.
AB  - Nitric oxide (NO) plays an important role in the regulation of cardiovascular
      function. S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl
      residues of proteins, resulting in the formation of S-nitrosothiols (SNOs), is a
      prevalent posttranslational protein modification involved in redox-based cellular
      signaling. Under physiologic conditions, protein S-nitrosylation and SNOs provide
      protection preventing further cellular oxidative and nitrosative stress. However,
      oxidative stress and the resultant dysfunction of NO signaling have been
      implicated in the pathogenesis of cardiovascular diseases.

PMID- 16987025
TI  - The role of apoptosis signal-regulating kinase 1 in cardiomyocyte apoptosis.
AB  - Apoptosis signal-regulating kinase 1 (ASK1), a serine/threonine protein kinase,
      is a reactive oxygen species-sensitive mitogen-activated protein kinase kinase
      kinase and activates both p38 and c-Jun N-terminal kinase pathways. Two isoforms
      of thioredoxin (Trx), cytosolic and mitochondrial Trx (Trx1 and Trx2,
      respectively), have been identified in mammalian cells. Trx1 was initially
      identified as an ASK1-binding protein. Trx1 and Trx2 bind directly to the N
      terminal regulatory domain of ASK1 and inhibit ASK1-dependent apoptosis. Numerous
      other proteins interact with ASK1 and regulate its activity. In cardiomyocytes,
      ASK1 is involved not only in cardiac apoptosis, leading to cardiac remodeling,
      but also in cardiac hypertrophy as well as nonapoptotic cardiomyocyte death.

PMID- 16987026
TI  - Mitochondrial oxidative stress, DNA damage, and heart failure.
AB  - Recent experimental and clinical studies have suggested that oxidative stress is
      enhanced in heart failure. The production of oxygen radicals is increased in the
      failing heart, whereas antioxidant enzyme activities are preserved as normal.
      Mitochondrial electron transport is an enzymatic source of oxygen radical
      generation and also a target of oxidant-induced damage. Chronic increases in
      oxygen radical production in the mitochondria can lead to a catastrophic cycle of
      mitochondrial DNA (mtDNA) damage as well as functional decline, further oxygen
      radical generation, and cellular injury. Reactive oxygen species induce myocyte
      hypertrophy, apoptosis, and interstitial fibrosis by activating matrix
      metalloproteinases. These cellular events play an important role in the
      development and progression of maladaptive cardiac remodeling and failure.
      Therefore, mitochondrial oxidative stress and mtDNA damage are good therapeutic
      targets. Overexpression of mitochondrial transcription factor A (TFAM) could
      ameliorate the decline in mtDNA copy number and preserve it at a normal level in
      failing hearts. Consistent with alterations in mtDNA, the decrease in oxidative
      capacities was also prevented. Therefore, the activation of TFAM expression could
      ameliorate the pathophysiologic processes seen in myocardial failure. Inhibition
      of mitochondrial oxidative stress and mtDNA damage could be novel and potentially
      very effective treatment strategies for heart failure.

PMID- 16987027
TI  - Reactive oxygen intermediates and signaling through kinase pathways.

PMID- 16987028
TI  - Molecular pathways leading to oxidative stress-induced phosphorylation of Akt.
AB  - Oxidative stress can activate a variety of intracellular signaling pathways. The
      authors previously reported the CaM-K inhibitor KN-93 inhibited hydrogen peroxide
      induced phosphorylation of Akt on threonine 308 (T308). In this report they
      demonstrate that phosphorylation of T308 in response to hydrogen peroxide
      treatment is not inhibited by LY294002, suggesting that phosphorylation of this
      residue in response to oxidative stress is largely PI3K independent. In contrast,
      hydrogen peroxide-induced phosphorylation of Akt on serine 473 (S473) was
      downregulated by both PI3K and CaM-K inhibition, indicating that hydrogen
      peroxideinduced phosphorylation of Akt on S473 was largely dependent on both PI3K
      and a CaM-K activity. Further, it is reported that p56(Lck) had a substantial
      role in hydrogen peroxide-induced phosphorylation of S473, but only a minimal
      role in hydrogen peroxide-induced phosphorylation of T308. These data suggest
      that in response to hydrogen peroxide, two pathways are activated in Jurkat T
      lymphocytes that converge to result in the phosphorylation of Akt on S473 and
      T308. One pathway involves the CaM-Ks that may directly phosphorylate Akt on
      T308. In this pathway, neither the Src kinases nor PI3K are required. The other
      pathway mediated by hydrogen peroxide results in the phosphorylation of Akt on
      S473 and requires CaM-K, PI3K, and Src activity.

PMID- 16987029
TI  - Reactive oxygen species signaling in plants.
AB  - The evolution of aerobic metabolism such as respiration and photosynthesis
      resulted in the generation of reactive oxygen species (ROS). A common property of
      all ROS types is that they can cause oxidative damage to proteins, DNA, and
      lipids. This toxicity of ROS explains the evolution of complex arrays of
      nonenzymatic and enzymatic detoxification mechanisms in plants. However,
      increasing evidence indicates that plants also make use of ROS as signaling
      molecules for regulating development and various physiological responses. In this
      review, novel insights into the mechanisms of how plants sense and respond to ROS
      are discussed in the context of the biological effects and functions of ROS in
      plants.

PMID- 16987030
TI  - The redox regulation of PI 3-kinase-dependent signaling.
AB  - Signal transduction via PI 3-kinases plays an important role in regulating the
      cellular processes of cell growth, survival, proliferation, and motility. The
      stimulated generation of reactive oxygen species is a necessary component of the
      signal transduction mechanisms by which many growth factors and cytokines
      activate this signaling pathway and elicit their cellular responses. Evidence now
      supports the oxidative inactivation of both tyrosine phosphatases acting upstream
      of PI 3-kinase, and of the lipid phosphatase PTEN as components of the normal
      stimulated regulation of PI 3-kinase signaling. However, the effects of chronic
      oxidative stress appear rather different, particularly a proposed role for
      nitrosylation of Akt and other targets leading to inhibition of PI 3-kinase
      signaling during diabetic insulin resistance in muscle. Recently, evidence has
      also begun to emerge, indicating that physiological redox signaling may display
      the same tight spatial and temporal specificity as seen with many other signal
      transduction systems in terms of targeting individual proteins for modification,
      and of enzymatic reversal mechanisms. This review will focus upon the details of
      these and other roles for reactive oxygen and nitrogen species in the regulation
      of PI 3-kinase signaling, both during acute stimulation and chronic oxidative
      stress, and the evidence for their significance.

PMID- 16987031
TI  - Reactive oxygen species-induced activation of the MAP kinase signaling pathways.
AB  - An abundance of scientific literature exists demonstrating that oxidative stress
      influences the MAPK signaling pathways. This review summarizes these findings for
      the ERK, JNK, p38, and BMK1 pathways. For each of these different MAPK signaling
      pathways, the following is reviewed: the proteins involved in the signaling
      pathways, how oxidative stress can activate cellular signaling via these
      pathways, the types of oxidative stress that are known to induce activation of
      the different pathways, and the specific cell types in which oxidants induce MAPK
      responses. In addition, the functional outcome of oxidative stress-induced
      activation of these pathways is discussed. The purpose of this review is to
      provide the reader with an overall understanding and appreciation of oxidative
      stress-induced MAPK signaling.

PMID- 16987032
TI  - Redox-sensitive kinases of the nuclear factor-kappaB signaling pathway.
AB  - NF-kappaB is an inducible transcription factor that plays a role in the
      expression of over one hundred genes involved in immunity, inflammation,
      proliferation, and in defense against apoptosis. NF-kappaB has been known to be
      redox regulated for some time and is a direct target for oxidation that can
      affect its ability to bind to DNA. Reactive oxygen species (ROS) have been
      identified as second messengers in cells, and play a role in receptor signaling
      and posttranslation modification of signaling molecules. These posttranslation
      modifications include oxidations of critical cysteines to sulfenic acids or mixed
      disulfides, which can affect the activity of proteins. Many kinases involved in
      direct or indirect activation of NF-kappaB are affected by oxidants and
      therefore, have the potential to alter NF-kappaB activity. This review will
      provide a summary of the NF-kappaB family, their activation and regulation,
      followed by a summary of cytoplasmic and nuclear kinases in this pathway whose
      activity is affected by oxidants. Additionally, recent investigations have
      revealed that the JNK signaling pathway, which is known to be redox regulated,
      and pro-apoptotic, is inhibited by NF-kappaB signaling. The crosstalk of NF
      kappaB with other signaling pathways is therefore critical for cellular fate,
      notably survival or cell death under oxidative conditions, and will also be
      reviewed.

PMID- 16987033
TI  - Activation of the calcium/calmodulin-dependent protein kinases as a consequence
      of oxidative stress.
AB  - Oxygen radicals have diverse effects on cells. In many cases, exposure to
      reactive oxygen intermediates (ROI) can induce cell death. Conversely, there is
      also evidence that suggests oxygen radicals can activate signaling pathways that
      are thought to prevent cell death. In this review, the authors discuss the
      finding that hydrogen peroxide and ROI-generating treatments trigger the
      activation of the calcium/calmodulin-dependent kinases (CaM-kinases), and the
      potential role this activation has in preventing apoptosis. Evidence is presented
      that CaM-kinase activation occurs by both calcium dependent- and independent
      pathways in response to ROIs. In addition, the idea is discussed that ROIs have
      the potential to lead to the phosphorylation of calmodulin and through this
      mechanism potentiate the activation of the CaM-kinases. The concept that
      inhibition of the CaM-kinases as a mechanism to sensitize cells to the damaging
      effects of ROIs is also presented. Contrasting these studies, evidence is
      presented that exposure of the CaM-kinases directly to hydrogen peroxide also has
      the apparent ability to inhibit their activity.

PMID- 16987034
TI  - Regulation of signal transduction through protein cysteine oxidation.
AB  - The production of reactive oxygen species (ROS) accompanies many signaling
      events. Antioxidants and ROS scavenging enzymes in general have effects that
      indicate a critical role for ROS in downstream signaling, but a mechanistic
      understanding of the contribution of ROS as second messengers is incomplete.
      Here, the role of reactive oxygen species in cell signaling is discussed,
      emphasizing the ability of ROS to directly modify signaling proteins through
      thiol oxidation. Examples are provided of protein thiol modifications that
      control signal transduction effectors that include protein kinases, phosphatases,
      and transcription factors. Whereas the effects of cysteine oxidation on these
      proteins in experimental systems is clear, it has proven more difficult to
      demonstrate these modifications in response to physiologic stimuli. Improved
      detection methods for analysis of thiol modification will be essential to define
      these regulatory mechanisms. Bridging these two areas of research could reveal
      new regulatory mechanisms in signaling pathways, and identify new therapeutic
      targets.

PMID- 16987035
TI  - Thioredoxin target proteins in chloroplast thylakoid membranes.
AB  - In recent years, impressive progress has been made in the identification of
      thioredoxin-linked proteins. However, due to technical difficulties inherent in
      working with hydrophobic proteins, identifications so far have been restricted to
      proteins in the soluble fraction. Thus, our knowledge of redox regulated membrane
      proteins is quite limited. To gain information in this area, the authors have
      applied an adaptation of the approach based on the fluorescent thiol probe
      monobromobimane (mBBr) to identify redox-linked proteins of chloroplast
      thylakoids. By application of this procedure, 14 potential membrane-bound
      thioredoxin target proteins were identified, including seven new candidates
      functional in processes associated with photosynthetic electron flow, ATP
      synthesis, and Photosystem II/Photosystem I state transitions.

PMID- 16987036
TI  - Overexpression of redox-active protein thioredoxin-1 prevents development of
      chronic pancreatitis in mice.
AB  - Chronic pancreatitis (CP) is considered to result from repetitive pancreatic
      injury, and sustained production of various proinflammatory cytokines and
      chemokines are closely involved in its pathogenesis. Monocyte chemoattractant
      protein 1 (MCP-1), a member of the CC chemokine family, is believed to contribute
      to the progression of CP through monocyte/macrophage recruitment. This study
      aimed to clarify the protective role of thioredoxin-1 (TRX-1), a redox-regulating
      protein with antioxidative activity, in MCP-1 production and pancreatic fibrosis
      using a CP model in transgenic mice overexpressing TRX-1 (TRX-1-TG mice) and
      wildtype C57BL/6 mice. Experimental CP was induced by repeated administration of
      cerulein and lipopolysaccharide for 6 weeks. In TRX-1-TG mice, pancreatic atrophy
      was ameliorated, and histologically detectable inflammatory cell infiltration,
      glandular atrophy, and pseudotubular complex formation were suppressed.
      Overexpression of TRX-1 also attenuated pancreatic fibrosis and suppressed the
      activation of pancreatic stellate cells. Serum levels of MCP-1 and pancreatic
      expression of transforming growth factor-beta, platelet-derived growth factor,
      and MCP-1 were reduced in TRX-1-TG mice compared with levels in wild-type mice.
      Overexpression of TRX-1 also reduced H(2)O(2)-induced MCP-1 production in
      isolated pancreatic acinar cells. These results indicate that TRX-1 can
      potentially attenuate pancreatic fibrosis via the suppression of oxidative stress
      and MCP-1-mediated chronic inflammation.

PMID- 16987037
TI  - Erythrocytes with T-state-stabilized hemoglobin as a therapeutic tool for
      postischemic liver dysfunction.
AB  - This study aimed to examine if T-state stabilization of hemoglobin in
      erythrocytes could protect against postischemic organ injury. Human erythrocytes
      containing three different states of Hb allostery were prepared: control Hb
      (hRBC), CO-Hb that is stabilized under R-state with the 6-coordinated prosthetic
      heme (CO-hRBC), and alpha-NO-deoxyHb stabilized under T-state (alpha-NO-hRBC). To
      prepare alpha-NO-RBC, deoxygenated RBC was treated with FK409, a thiol-free NO
      donor, at its half molar concentration to that of Hb; this procedure resulted in
      the 5-coordinated NO binding on the alpha-subunit heme, as judged by electron
      spin resonance spectrometry. Rats were subject to 20 min systemic hemorrhage to
      maintain mean arterial pressure at 40 mm Hg, and reperfused with one of hRBCs.
      This protocol for ischemia, followed by 60 min reperfusion with physiological
      saline, caused modest metabolic acidosis and cholestasis. Administration of hRBC
      or COhRBC significantly attenuated cholestasis and improved acidosis. Rats
      treated with alpha-NO-hRBC exhibited greater recovery of metabolic acidosis and
      bile excretion than those treated with hRBC or CO-hRBC, displaying the best
      outcome of local oxygen utilization in hepatic lobules. Half-life time of alpha
      NO-RBC administered in vivo was approximately 60 min. These results suggest that
      T-state Hb stabilization by NO serves as a stratagem to treat postischemic organ
      dysfunction.

PMID- 16987038
TI  - Intracellular redox regulation by the family of small GTPases.
AB  - There is growing experimental evidence that the production of intracellular
      reactive oxygen species (ROS) represents a tightly regulated process. In
      particular, numerous observations have suggested a role for the Ras superfamily
      of small GTPases in redox regulation. This article reviews the evidence that ROS
      can serve as important downstream effectors for both Ras and Rac proteins. Given
      the prominent role these proteins play in regulating growth, senescence, and
      transformation, understanding the role of the small GTPase family in redox
      regulation may significantly alter our current concepts as to how free radicals
      contribute to diverse processes from aging to cancer.

PMID- 16987039
TI  - Redefining oxidative stress.
AB  - Oxidative stress is often defined as an imbalance of pro-oxidants and
      antioxidants, which can be quantified in humans as the redox state of plasma
      GSH/GSSG. Plasma GSH redox in humans becomes oxidized with age, in response to
      oxidative stress (chemotherapy, smoking), and in common diseases (type 2
      diabetes, cardiovascular disease). However, data also show that redox of plasma
      GSH/GSSG is not equilibrated with the larger plasma cysteine/cystine (Cys/CySS)
      pool, indicating that the "balance" of pro-oxidants and antioxidants cannot be
      defined by a single entity. The major cellular thiol/disulfide systems, including
      GSH/GSSG, thioredoxin- 1 (-SH(2)/-SS-), and Cys/CySS, are not in redox
      equilibrium and respond differently to chemical toxicants and physiologic
      stimuli. Individual signaling and control events occur through discrete redox
      pathways rather than through mechanisms that are directly responsive to a global
      thiol/disulfide balance such as that conceptualized in the common definition of
      oxidative stress. Thus, from a mechanistic standpoint, oxidative stress may be
      better defined as a disruption of redox signaling and control. Adoption of such a
      definition could redirect research to identify key perturbations of redox
      signaling and control and lead to new treatments for oxidative stress-related
      disease processes.

PMID- 16987040
TI  - Redox regulation of human thioredoxin network.
AB  - Oxidative stresses are largely mediated by intracellular protein oxidations by
      reactive oxygen species (ROS). Host cells are equipped with antioxidants that
      scavenge ROS. The cellular reduction/oxidation (redox) balance is maintained by
      ROS and antioxidants. Accumulating evidence suggests that the redox balance plays
      an important role in cellular signaling through the redox modification of
      cysteine residues in various important components of the signal transduction
      pathway. Thioredoxin (TRX) is a small protein playing important roles in cellular
      responses, including cell growth, cell cycle, gene expression, and apoptosis, to
      maintain the redox circumstance. Moreover, many recent papers have shown that the
      redox regulation by TRX is deeply involved in the pathogenesis of various
      oxidative stress-associated disorders. This review focuses on TRX and its related
      molecules, and discusses the role of TRX-dependent redox regulation in oxidative
      stress-induced signal transduction.

PMID- 16987041
TI  - Thioredoxin-1 suppresses systemic inflammatory responses against cigarette
      smoking.
AB  - Thioredoxin-1 (TRX) is a small redox-active protein with antioxidative effects
      and redox-regulating functions. Cigarette smoking is a major etiological factor
      in the pathogenesis of a variety of diseases and recruits systemic immune and
      inflammatory responses. This report demonstrates that TRX attenuates the systemic
      inflammatory responses induced by cigarette smoking. The mRNA expressions of
      tumor necrosis factor alpha (TNF-alpha) and macrophage migration inhibitory
      factor (MIF) were suppressed in the spleen of TRX overexpressing transgenic mice
      (TRX-tg) exposed to cigarette smoking, compared with control C57BL/6 mice. In
      addition, protein carbonylation, a marker of cellular protein oxidation, was
      enhanced by cigarette smoking in the tissues of heart and liver in control mice
      more than in TRX-tg mice. These findings suggest that TRX may suppress the
      systemic inflammatory responses against cigarette smoking.

PMID- 16987044
TI  - Treating HIV infection with one pill per day.

PMID- 16987042
TI  - Copper activates the NF-kappaB pathway in vivo.
AB  - Previous results indicated that intravenous injection of copper in the form of a
      copper-histidine complex in rats triggers the transcriptional induction of the
      inducible form of nitric oxide synthase (NOS-II). Here, the authors demonstrate
      that copper activates the transcription factor NF-kappaB in the liver and lung
      tissues of rats, and that this effect is mediated by oxidative stress, since all
      copper-induced changes, which include histological alterations, formation of
      nitrotyrosines, vascular pressure drop, production of tumor necrosis factor-alpha
      (TNF-alpha), induction of NOS-II and nitrites, are readily prevented by
      pretreatment of the animals with the antioxidant tempol. By using electrophoretic
      mobility shift assays, the p50/p65 dimer and higher molecular weight aggregates
      have been found to be involved in the copper-induced NF-kappaB activation. COX-2,
      a NF-kappaBdependent gene involved in the inflammatory response, was also
      transcriptionally induced by copper, this effect being reduced in the presence of
      tempol. These results suggest that a physiopathological status, characterized by
      hypercupremic situations, may lead to the onset of inflammation through
      production of ROS and activation of NF-kappaB.

PMID- 16987045
TI  - Long-term follow-up of patients with initial early virologic failure after being
      treated with once-daily tenofovir/abacavir/lamivudine.

PMID- 16987046
TI  - Amoebic hepatic abscesses in an HIV-positive patient.
AB  - Herein we report the case of hepatic amoebic abscesses in an HIV-positive Italian
      seaman with a history of promiscuous heterosexual intercourse. In October 2004,
      the patient was hospitalized because of fever and recurring abdominal pain.
      Abdominal ultrasonography revealed six hepatic hypoechoid oval lesions with
      hyperechoid margins. Stool samples were negative for parasites and bacteria, and
      serology for Entamoeba histolytica was also negative. Therapy with meropenem plus
      levofloxacin was initiated. After a partial resolution of clinical symptoms and
      reduction of three hepatic lesions, the patient was again hospitalized in
      December 2004, because of recurring intense pain at the right hypochondrium and
      fever. At this time, one hepatic lesion at the sixth segment was enlarged, two
      lesions were unchanged, and the remaining three smaller abscesses were resolved.
      Serum antibodies for E. histolytica and amoebic antigens on the largest abscess
      drainage were positive; moreover, E. histolytica was also identified on drainage
      fluid with polymerase chain reaction (PCR). Therapy with metronidazole followed
      by paromomycin improved both symptoms and radiographic images. This case report
      suggests that in HIV-infected patients, invasive amoebiasis should be considered
      and atypical aspects, such as multiple hepatic lesions, delayed positivity of
      serology for E. histolytica, and possible bacterial superinfection should be
      evaluated.

PMID- 16987047
TI  - Predictors for hematopoietic growth factors use in HIV/HCV-coinfected patients
      treated with peginterferon alfa 2b and ribavirin.
AB  - HIV/hepatitis C virus (HCV)-coinfected individuals have accelerated liver
      disease, increased drug toxicities, and modest responses to peginterferon and
      ribavirin. Hematologic toxicities necessitating dose reduction or discontinuation
      are limiting factors to HCV treatment in the coinfected patient. This study aimed
      to identify predictors for the need of filgrastim and darbepoetin to manage
      hematologic toxicities so as to maintain patients on full doses of study drugs
      for the duration of study. The primary study was a single-center, open-label,
      prospective study to evaluate the safety, efficacy, and viral kinetics of 48-week
      peginterferon alfa 2b and ribavirin in HIV/HCV-coinfected patients. Complete
      blood count was monitored at baseline, days 3, 7, 10, 14, and then weekly for the
      first month, fortnightly until week 8, then monthly from week 12 to 48.
      Filgrastim was initiated when absolute neutrophil count (ANC) fell below 750
      cells/mm(3) and darbepoetin was used when hemoglobin dropped to less than 10
      g/dL. All patients experienced decrease in ANC and hemoglobin. Twenty of 30
      (66.6%) of patients required hematopoeitic growth factors, 15 (50%) received
      filgrastim, and 12 (40%) received darbepoetin. Seven (23.3%) required both.
      Baseline ANC of less than 2250 cells per millimeter and negative rate of change
      of hemoglobin on day 3 of therapy were excellent predictors for filgrastim and
      darbepoetin use, respectively. Supplemental growth factors were associated with
      substantial increase in overall cost for HCV treatment. Larger clinical trials
      will be needed to address the cost effectiveness of supplemental growth factor
      use in the HIV/HCV-coinfected patients.

PMID- 16987048
TI  - Communicating indeterminate HIV Western blot test results to clients: an
      observational study of three community testing sites.
AB  - This study examined HIV test counselors' beliefs and practices regarding
      communicating indeterminate HIV test results to clients. There are many reasons
      for an indeterminate HIV antibody/ Western blot assay including early HIV
      infection, infection with other contagious diseases, autoimmune diseases, and
      second or subsequent pregnancies in women. Field observations of three community
      HIV testing sites and semistructured interviews with 16 HIV test counselors were
      conducted from August 2002 through June 2003. Counselors defined an indeterminate
      test result in different ways. They also presented several different theories of
      causation, yet failed to mention two potential causes of an indeterminate result,
      association with large animals and infection with other (non-HIV-1) HIV strains.
      Counselors' understanding of the meaning of an indeterminate HIV test result
      varied a great deal. Some counselors believed that an indeterminate result truly
      was ambiguous while others believed it was indicative of being either HIV
      positive or HIV-negative. Counselors' primary advice to clients who received an
      indeterminate result was to retest immediately without a waiting period.
      Counselors reported that communicating indeterminate test results to clients was
      a challenging task because clients who received such a result were confused,
      angry, and/or mistrustful. Results highlight the need for further research to
      provide reliable estimates of the extensiveness of indeterminate HIV test results
      and to further assess the nature of counselor and client responses to
      indeterminate test results.

PMID- 16987049
TI  - Durability of adherence to antiretroviral therapy on initial and subsequent
      regimens.
AB  - There is uncertainty regarding the durability of adherence to antiretroviral
      therapy. This study is a retrospective review of previously antiretroviral naive
      patients initiating therapy between 1997 and 2002. Antiretroviral adherence was
      calculated using prescription refill data and was analyzed over time on an
      initial regimen and on sequential antiretroviral regimens. Three hundred forty
      four patients were included. The median lengths of the first, second, and third
      regimens were stable at 1.7 years, 1.2 years, and 1.5 years, respectively (p =
      0.10). In multivariate analysis the factor most significantly associated with
      earlier initial regimen termination was poor adherence. On an initial regimen,
      adherence decreased over time and declined most rapidly in patients with the
      shortest regimens (4 to <16 months, -43% per year), followed by patients with
      intermediate regimen duration (16 to <28 months, -19% per year), and then
      patients with longer regimens (>/=28 months, -5% per year). In patients
      progressing to a third regimen, there was a trend toward decreasing adherence
      over successive regimens. In conclusion, sequential antiretroviral regimens are
      of similar lengths, with adherence being highly associated with first regimen
      duration. Adherence decreases during an initial regimen and on sequential
      antiretroviral regimens. Effective and durable interventions to prevent declining
      adherence are needed.

PMID- 16987050
TI  - Supporting adherence to highly active antiretroviral therapy and protected sex
      among people living with HIV/AIDS: the role of patient-provider communication in
      Rio de Janeiro, Brazil.
AB  - This exploratory study examined patient-provider communication dynamics regarding
      adherence to highly active antiretroviral therapy (HAART) and protective sexual
      behavior among people living with HIV/AIDS (PLWHA). We conducted 20 direct
      observations of routine consultations between PLWHA and care providers in two
      large public health clinics providing free HIV medications and clinical care to
      PLWHA in the greater Rio de Janeiro area of Brazil. Immediately after these
      observations, 20 semistructured in-depth interviews were conducted with
      observation participants regarding their communication with providers, overall
      clinic experience, and questions and concerns about adherence to HAART and safe
      sex. Findings from observations showed that patient-provider communication
      focused almost exclusively on biomedical aspects of HIV-related treatment such as
      symptom management. In most observations, adherence to HAART was addressed.
      However, questions posed by providers regarding adherence were generally close
      ended and leading, discouraging an open exchange regarding potential difficulties
      related to adherence. HIV/sexually transmitted infection (STI)- related
      protective behaviors were seldom addressed except when the patient displayed STI
      symptoms or was thought to be pregnant. In qualitative interviews, patients
      generally reported satisfaction with their providers, but also reported a variety
      of concerns and challenges related to adherence to HAART and protective sexual
      behavior that were not expressed in patient-provider interactions. We conclude
      that one way in which adherence to HAART and protective sexual behavior among
      PLWHA could be facilitated is by improving patient- provider communication on
      these topics, including increasing the frequency of openended, nonjudgmental
      dialogue initiated by care providers.

PMID- 16987051
TI  - Barriers to accessing antiretroviral therapy in Kisesa, Tanzania: a qualitative
      study of early rural referrals to the national program.
AB  - This community-based, qualitative study conducted in rural Kisesa District,
      Tanzania, explores perceptions and experiences of barriers to accessing the
      national antiretroviral programme among self-identified HIV-positive persons.
      Part of wider operations research around local introduction of HIV therapy, the
      study involved consultation with villagers and documented early referrals'
      progress through clinical evaluation and, if eligible, further training and drug
      procurement. Data collection consisted of 16 participatory group discussions with
      community members and 18 in-depth interviews with treatment-seekers. Although
      participants welcomed antiretroviral therapy, they feared that transportation and
      supplementary food costs, the referral hospital's reputation for being unfriendly
      and confusing, and difficulties in sustaining long-term treatment would limit
      accessibility. Fear of stigma framed all concerns, posing challenges for
      contacting referrals who did not want their status disclosed or expressed
      reluctance to identify a "treatment buddy" as required by the programme. To
      mitigate logistical barriers, transportation costs were paid and hospital visits
      facilitated. Participants reported satisfaction with eligibility testing, finding
      the process easier than anticipated. Most were willing to join a support group
      and some changed attitudes toward disclosure. However, both experienced and
      anticipated discrimination continue to hinder widespread antiretroviral therapy
      (ART) uptake. While simple measures to reduce perceived barriers improved initial
      access to treatment and helped overcome anxiety among early referrals, pervasive
      stigma remains the most formidable barrier. Encouraging successful referrals to
      share their positive experiences and contribute to nascent community
      mobililzation could start to address this seemingly intractable problem.

PMID- 16987052
TI  - Integrase combination effective.

PMID- 16987053
TI  - AIDS conference opening.

PMID- 16987055
TI  - Viral hijacking of cellular ubiquitination pathways as an anti-innate immunity
      strategy.
AB  - Viruses are obligate parasites of host cells. Virus-host coevolution has selected
      virus for growth despite antiviral defenses set up by hosting cells and
      organisms. Ubiquitin conjugation onto proteins, through a cascade of reactions
      mediated by E1 (ubiquitin-activating enzyme) and E2 and E3 (ubiquitin-
      conjugating ligases), is one of the major regulatory systems that, in particular,
      tightly controls the concentration of cellular proteins by sorting them for
      degradation. The combined diversity of E2 and E3 ligases ensures the
      selective/specific ubiquitination of a large number of protein substrates within
      the cell interior. Therefore it is not surprising that several viruses encode
      proteins with E3 ubiquitin ligase activities that target cellular proteins
      playing a key role in innate antiviral mechanisms.

PMID- 16987056
TI  - Increased CD154 expression in uninfected infants born to HIV-positive mothers
      exposed to antiretroviral prophylaxis.
AB  - Although prevention of mother-to-child HIV transmission by antiretroviral drugs
      has been shown to be effective, the short- and long-term effects of treatment are
      not well known. Several reports suggest that antiretroviral drugs act not only by
      inhibiting viral replication, but also by improving antiviral immunity. In
      particular, treatment with nucleoside analogs was found to increase CD40 ligand
      (CD40L; CD154) levels, an inducible molecule expressed on activated T
      lymphocytes. The present study investigated potential immunostimulatory effects
      of antiretroviral treatment (ART) in uninfected HIV-exposed infants, receiving
      either ante- or postnatal therapy to reduce the transmission rate. To this end,
      we analyzed CD40L expression in unstimulated lymphocytes from peripheral blood
      samples of uninfected infants vertically exposed to HIV and subjected to ART. The
      CD45 PanLeucogating strategy was applied in flow cytometry to analyze the
      lymphocytes of 41 cases and 64 age-matched infants, taken as control. We found
      increased CD154 expression on both CD4+ and CD8+ lymphocytes in ART-treated
      infants, compared with the controls. CD154 was apparently functional, because the
      expression of CD86 on monocytes was enhanced; moreover, inhibition of the CD40
      CD40L interaction produced downmodulation of CD86. From these results, we
      conclude that CD4+ and CD8+ lymphocytes of HIV-exposed noninfected infants, who
      have been exposed to antiretroviral drugs in fetal and early life, display
      enhanced CD154 expression and costimulatory activity.

PMID- 16987057
TI  - Serological profiles after consecutive experimental infections of pigs with
      European H1N1, H3N2, and H1N2 swine influenza viruses.
AB  - Swine influenza viruses (SIVs) of H1N1, H3N2, and H1N2 subtypes, with
      antigenically different hemagglutinins, are currently cocirculating in pigs in
      Europe. This study aimed to determine whether the hemagglutination inhibition
      (HI) test, which is the primary serological test for SIV, is sufficiently
      specific to discriminate between infections with the three subtypes. In
      experiment 1, pigs were consecutively inoculated with European H1N1, H3N2, and
      H1N2 SIVs by the intranasal route, or with the respective subtypes only. In a
      second experiment, a commercial, inactivated H1N1- and H3N2- based SIV vaccine
      was administered once to pigs previously infected with one to three SIV subtypes
      or to influenza-naive pigs. Sequential serum samples were examined in HI and
      virus-neutralizing (VN) tests to the three strains used for pig inoculations. Of
      the 160 sera collected after infection with one or two SIV subtypes, only 8
      showed cross-reactive antibodies to the remaining subtype(s) in the HI test, and
      11 in the VN test. Consecutive inoculations with H1N1 and H1N2 or vice versa were
      followed by a significant rise in preexisting antibody titers to the first
      subtype after the second inoculation. When dually infection-immune pigs were
      inoculated with the third, remaining SIV subtype, nasal virus excretion was
      undetectable or reduced and the serological response was absent to moderate. A
      single vaccination of infection-immune pigs resulted in a dramatic rise in HI and
      VN antibody titers to any of the previously encountered subtypes, whereas SIV
      naive pigs barely seroconverted. Most important, pigs previously infected with
      H1N1 but not with H1N2 developed crossreactive antibodies to H1N2 after the
      vaccination. In conclusion, the HI test remains adequate for the differential
      diagnosis of infections with H1N1, H3N2, and H1N2 in European swine populations
      if it is properly used and if the SIV vaccination status is taken into account.

PMID- 16987058
TI  - Identification of a conserved epitope cluster in the N protein of porcine
      reproductive and respiratory syndrome virus.
AB  - In this study, 4 overlapping fragments and 12 overlapping peptides of the
      nucleocapsid (N) protein from porcine reproductive and respiratory syndrome virus
      (PRRSV) were expressed as glutathione S-transferase (GST) fusion proteins and
      used to probe a panel of 16 anti-N protein monoclonal antibodies (mAbs) by ELISA.
      The minimal epitope sequence of the following seven mAbs was determined by
      sequential deletion of terminal amino acid residues from each peptide: N2H7
      corresponded to H54FPLA58; N2F7 corresponded to K52PHFPLA58; and N1A2, N1E3,
      N1G4, and N2E5 were reactive against E51KPHFP56. Furthermore, a polypeptide
      containing this epitope cluster was recognized by PRRSV-immune pig serum by
      Western blot, suggesting that residues 51-58 represent an immunodominant region
      of the N protein. Sequence alignment revealed that these epitopes are well
      conserved among North American and European genotypes of PRRSV. These findings
      enhance our knowledge of the antigenic structure of N protein and may facilitate
      the development of better diagnostic methods for PRRSV.

PMID- 16987059
TI  - Herpes simplex virus genes Us3, Us5, and Us12 differentially regulate cytotoxic T
      lymphocyte-induced cytotoxicity.
AB  - Many viruses, including Herpes Simplex Virus (HSV), have developed strategies to
      avoid detection by cytotoxic T lymphocytes (CTLs). In this article, we evaluated
      the role of individual HSV-1 genes in preventing cytolysis and apoptosis, and in
      decreasing viral yield after CTL exposure of HSV-infected fibroblasts, using
      viruses deleted for the immune evasion gene Us12 or one of the two antiapoptotic
      genes Us3 and Us5. To evaluate CTL-mediated apoptosis, we used a flow cytometry
      assay measuring active caspase-3 in target cells. This assay was more sensitive
      than the chromium release assay used to evaluate cytolysis, and measured a
      different aspect of CTL cytotoxicity. Although virus with deletion of Us12 was
      markedly defective in the ability to prevent lysis of target fibroblasts, it
      retained most of its ability to protect target fibroblasts from CTL-induced
      apoptosis. Virus with deletion of Us3 was also defective in the ability to
      prevent lysis of target fibroblasts, yet such virus protected target fibroblasts
      from CTL-induced apoptosis as well as wild-type viruses. In contrast, Us5-deleted
      virus showed defects in the ability to protect target fibroblasts from both
      cytolysis and apoptosis after CTL attack. In addition, the replication of Us12
      deleted virus was reduced compared with wild-type virus in fibroblasts subjected
      to CTL attack 6 h after infection, but showed equivalent replication when CTL
      attack occurred later. In contrast, Us3- or Us5-deleted virus showed no
      measurable defect in their ability to replicate in fibroblasts under CTL attack.
      Our data suggest that cytolysis, apoptosis, and viral yield do not necessarily
      correlate in infected cells under CTL attack. Furthermore, the Us3, Us5, and Us12
      viral genes each have unique inhibitory effects on the different T lymphocyte
      cytotoxic effects. Taken together, these results suggest that HSV evasion of
      cellular immunity is multifacterial and complex, and relies on the partially
      redundant activities of various individual HSV proteins.

PMID- 16987060
TI  - Differential regulation of CXCR4 and CCR5 expression by interleukin (IL)-4 and IL
      13 is associated with inhibition of chemotaxis and human immunodeficiency Virus
      (HIV) type 1 replication but not HIV entry into human monocytes.
AB  - Chemokine receptors CXCR4 and CCR5 play a key role in Human Immunodeficiency
      Virus (HIV) entry into CD4+ monocytic cells. Alteration in the expression levels
      of these receptors by immunoregulatory cytokines may influence viral entry and
      hence susceptibility to HIV infection, viral tropism, and disease progression.
      Helper T cell type 2 (Th2) cytokines interleukin (IL)-4 and IL-13, which share a
      subunit of their receptor components and exhibit similar biological effects, have
      been shown to play a key role in HIV infection and disease progression. In this
      study, we investigated the effects of IL-4 and IL-13 on the expression of CXCR4
      and CCR5, and the biological implications of alteration of CXCR4 and CCR5
      regulation on monocytic cells with respect to their migration in response to
      chemokines, HIV entry, and its replication. The results suggest that both IL-4
      and IL-13 inhibited the expression of CXCR4, in contrast to CCR5, which was
      inhibited by IL-13 alone. The downregulation of CXCR4 and CCR5 was
      correspondingly associated with the inhibition of their respective ligand-induced
      chemotaxis. Although IL-13 inhibited the expression of both CXCR4 and CCR5, this
      downregulation of chemokine receptor expression was not sufficient to prevent
      virus entry. Furthermore, both IL-4 and IL-13 inhibited viral replication in
      monocytic cells, suggesting that inhibition of chemokine receptor expression per
      se by these cytokines may not be sufficient to prevent virus entry, and
      indicating these cytokines may be inhibiting viral replication by targeting
      pathways subsequent to virus entry.

PMID- 16987061
TI  - Apoptosis of epitope-specific antiretroviral cytotoxic T lymphocytes via Fas
      ligand-Fas interactions.
AB  - C57BL/6 (B6; H-2b) mice are capable of mounting a vigorous AKR/Gross Murine
      Leukemia Virus (MuLV)-specific cytotoxic T lymphocyte (CTL) response to AKR/Gross
      MuLVs whereas AKR.H- 2b congenic mice, although carrying the responder H-2b major
      histocompatibility haplotype, are specifically nonresponsive. Furthermore, when
      viable AKR.H-2b spleen cells are cocultured with primed responder B6 antiviral
      precursor CTLs, the AKR.H-2b cells function as "veto" cells that actively mediate
      the inhibition by apoptosis of B6 antiviral CTL generation in a contact
      dependent, MHC-restricted, and veto cell Fas ligand (FasL)/responder T cell Fas
      dependent manner. In the present study we show that antigen-specific, antiviral
      CTLs that survive apoptotic inhibition by AKR.H-2b veto cells display a less
      activated cell surface phenotype, and are less able to bind specific MHC-peptide
      tetramers, including on a per-T cell receptor (TcR) basis. In addition, surviving
      antiviral CTLs also appeared to be functionally deficient, based on both their
      reduced ability to lyse specific target cells and to produce interferon (IFN)
      gamma. Carboxyfluorescein diacetate succinimidyl ester staining confirmed that
      AKR/Gross MuLV-specific CTLs proliferated less extensively when AKR.H-2b veto
      cells were included in cocultures. AKR/Gross MuLV-specific effector CTLs as well
      as memory CTLs were each efficiently targeted for inhibition by AKR.H-2b veto
      cells. Attempts to enhance the quality of the priming by multiple in vivo
      immunizations did not alter the capacity of the AKR.H-2b cells to inhibit the
      antiviral CTL response. These results further characterize the nature of the
      interaction between veto cells and antiviral CTLs, and underscore the efficiency
      of veto cell-mediated inhibition of the CTL response.

PMID- 16987062
TI  - Mechanism for complement-mediated, antibody-dependent enhancement of human
      immunodeficiency virus type 1 infection in MT2 cells is enhanced entry through
      CD4, CD21, and CXCR4 chemokine receptors.
AB  - Some antibodies neutralize Human Immunodeficiency Virus (HIV). However, antibody
      to HIV and complement can enhance HIV replication if cells express both
      complement receptors and CD4, a phenomenon described as complement-mediated,
      antibody-dependent enhancement (C'ADE). Although increased binding of opsonized
      virions has been reported, the mechanism by which C'ADE enhances HIV replication
      remains unproven. In this study, real-time polymerase chain reaction to detect
      HIV cDNA indicates that complement and anti-HIV antibodies enhance HIV entry 8-
      to 30- fold with similar increases in integrated provirus. Thus, complement
      increases HIV replication through a mechanism of enhanced entry. To further
      refine the mechanism of C'ADE, chemokine receptor antagonists were employed.
      JM2987, a CXCR4 chemokine receptor antagonist, blocked HIV infection and C'ADE;
      thus CD4, complement receptors, and CXCR4 chemokine receptors are required for
      enhanced entry of HIV into MT2 cells. Finally, anti-HIV immunoglobulin enhanced
      replication of not only group M clade B HIV but also group M clade D and group O
      isolates. These data demonstrate that antibodies mediating C'ADE of HIV infection
      are broadly reactive.

PMID- 16987063
TI  - Sustained conservation of CD4+ T cells in multiprotein triple modality-immunized
      rhesus macaques after intrarectal challenge with simian immunodeficiency virus.
AB  - As part of a European multicenter study designed to determine the optimal
      combination and order of a mixed-modality vaccine against acquired
      immunodeficiency syndrome, rhesus monkeys received a combination of three
      different vectors, all expressing the same Simian Immunodeficiency Virus (SIV)
      genes followed by mucosal challenge with highly pathogenic SIV. In the study
      reported here, animals were primed with DNA followed by one booster immunization
      with Semliki Forest Virus (SFV) and two immunizations with modified Vaccinia
      Ankara (MVA). To address the relevance of mucosal immunization, we compared
      systemic versus a combination of systemic and mucosal antigen application.
      Although all vaccinees became infected after intrarectal challenge with SIV, most
      (six of eight) were protected from profound loss of CD4+ cells. In addition,
      vaccinees showed lower viral loads than did controls (p < 0.05). Overall, these
      protective effects were more pronounced in those animals whose schedule included
      immunization via the mucosa. In summary, the vaccine regimen used here achieved
      one important criterion of efficacy: the suppression of disease development as
      indicated by conservation of CD4+ cells.

PMID- 16987064
TI  - Immunogenic variation between multiple HLA-A*0201-restricted, Hepatitis C Virus
      derived epitopes for cytotoxic T lymphocytes.
AB  - CD8+ cytotoxic T lymphocytes (CTLs) play a critical role in the immune control of
      Hepatitis C Virus (HCV) infection. In the current study, a number of HLA-A*0201
      restricted CTL epitopes derived from HCV were evaluated by examining the peptide
      binding affinity for major histocompatibility complex (MHC) class I molecules,
      the stability of peptide-MHC complexes, killing activities of peptide-induced
      CTLs, and frequencies of intracellular interferon (IFN)-gamma-positive CD8+ T
      cells. Among 24 peptides tested, 15 peptides induced high or medium killing
      activities of peptide-specific CTLs. Thirteen of the 15 peptides exhibited high
      or medium binding affinities for HLA-A*0201 molecules, indicating that the high
      binding affinity for MHC class I molecules is an important factor for
      immunogenicity. In contrast, the stability of peptide-MHC class I complexes was
      not correlated with killing activities of peptide-induced CTLs. Furthermore, only
      a limited number of peptides could induce high or medium frequencies of IFN-gamma
      producing CD8+ T cells, which were generally considered to play a crucial role
      for the clearance of HCV. Analyses of the immunogenicity of CTL epitopes such as
      in the current study should provide important information about the design of an
      efficient HCV vaccine that induces vigorous, sustained, and broad HCV-specific
      CTL responses.

PMID- 16987065
TI  - E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of
      human transforming growth factor beta1 promoter throughout Sp1 recognition
      sequence.
AB  - Human Papillomavirus (HPV) infection is the main etiologic agent of cervical
      cancer and HPV E6 and E7 oncogenes trans-regulate many cellular genes. An
      association between TGF-beta1 gene expression and cervical cancer development has
      been suggested; however, the mechanisms by which HPV influences TGF-beta1
      expression remain unclear. In the present study we analyzed the mechanism through
      which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta1 promoter in cervical
      tumor cells. Our results showed that E6 and E7 increased TGF-beta1 promoter
      activity. Furthermore, we identified a specific DNA sequence motif in the TGF
      beta1 core promoter that is responsible for trans-activation and that corresponds
      to the Sp1e-binding site associated with HPV-16 E6 and E7 oncoproteins.
      Mutational analysis showed that the Sp1e recognition site abolished the trans
      activation caused by E6 and E7. These results suggest a physical interaction and
      functional cooperation between viral oncoproteins and cellular regulatory
      elements of the TGF-beta1 promoter, and may explain the contribution of HPV-16 to
      TGF-beta1 gene expression in cervical cancer.

PMID- 16987066
TI  - In vivo expression of immunosuppressive cytokines in human papillomavirus
      transformed cervical cancer cells.
AB  - Genital human Papillomavirus infection is common and only a minor fraction of
      infected subjects develop progressing cervical epithelial lesions or cancer.
      Bypassing local immune responses is important for the development of cervical
      cancer. In this work we determined the cytokine pattern in samples from patients
      with cervical cancer. Thus, we examined the local mRNA expression profile of
      helper T cell type 1 (Th1), Th2, and Th3 cytokines in HPV-positive cervical
      cancer biopsies by reverse transcription-polymerase chain reaction. Our data
      indicate that 80% of the tumors expressed low levels of CD4 mRNA, with all of
      them expressing higher CD8 mRNA levels. Most tumors expressed interleukin (IL)-4
      and IL-10 mRNAs and, most importantly, all of them expressed transforming growth
      factor (TGF)-beta1 and interferon gamma mRNA. None of the tumors studied
      expressed IL-12, IL-6, or tumor necrosis factor (TNF) mRNA. Immunohistochemical
      analysis identified IL-10 only in tumor cells and koilocytic cells, but not in
      tumor-infiltrating lymphocytes, suggesting that IL-10-producing cells are those
      transformed by HPV. We found a correlation between immunostaining for IL-10
      protein and the level of IL-10 mRNA expression. Moreover, supernatants from HPV
      transformed cell cultures contained IL-10 and TGF- beta1. Our findings indicate a
      predominant expression of immunosuppressive cytokines, which might help
      downregulate tumor-specific immune responses in the microenvironment of the
      tumor. This information may be useful for cervical cancer immunotherapies or for
      therapeutic vaccine design against Human Papillomavirus.

PMID- 16987067
TI  - Protective cell-mediated immunity by DNA vaccination against Papillomavirus L1
      capsid protein in the Cottontail Rabbit Papillomavirus model.
AB  - Papillomavirus major capsid protein L1 has successfully stimulated protective
      immunity against virus infection by induction of neutralizing antibodies in
      animal models and in clinical trials. However, the potential impact of L1-induced
      protective cell-mediated immune (CMI) responses is difficult to measure in vivo
      because of the coincidence of anti-L1 antibody. In this study, we tested the
      hypothesis that L1 could activate CMI, using the Cottontail Rabbit Papillomavirus
      (CRPV)-rabbit model. A unique property of this model is that infections can be
      initiated with viral DNA, thus bypassing all contributions to protection via
      neutralizing anti-L1 antibody. DNA vaccines containing either CRPV L1, or
      subfragments of L1 (amino-terminal two-thirds of L1 [L1N] and the
      carboxylterminal two-thirds of L1 [L1C]), were delivered intracutaneously into
      rabbits, using a gene gun. After three booster immunizations, the rabbits were
      challenged with several viral DNA constructs: wild-type CRPV, CRPV L1ATGko (an L1
      ATG knockout mutation), and CRPV-ROPV hybrid (CRPV with a replacement L1 from
      Rabbit Oral Papillomavirus). Challenge of L1 DNA-vaccinated rabbits with wild
      type CRPV resulted in significantly fewer papillomas when compared with challenge
      with CRPV L1ATGko DNA. Significantly smaller papillomas were found in CRPV L1-,
      L1N-, and L1C-vaccinated rabbits. In addition, rabbits vaccinated with either L1
      or L1N grew significantly fewer and smaller papillomas when challenged with CRPV
      ROPV hybrid DNA. Therefore, CRPV L1 DNA vaccination induced CMI responses to CRPV
      DNA infections that can contribute to protective immunity. Cross-protective
      immunity against CRPV L1 and ROPV L1 was elicited in these CRPV L1- and
      subfragment-vaccinated rabbits.

PMID- 16987068
TI  - Immune regulation of transgene expression in the brain: B cells regulate an early
      phase of elimination of transgene expression from adenoviral vectors.
AB  - Cellular immune mechanisms that regulate viral gene expression within infected
      brain cells remain poorly understood. Previous work has shown that systemic
      immunization against adenovirus after vector delivery to the brain results in
      complete loss of brain cells infected by adenoviral vectors. Although T cells
      play an important role in this process, we demonstrate herein that B cells also
      significantly regulate transgene expression from the CNS. After the systemic
      immunization against adenovirus of animals injected via the brain with an
      adenoviral vector 30 days earlier, we uncovered substantial infiltration by CD19+
      B cells of the area of the brain transduced by the virus. This suggests the
      involvement of B cells in the adaptive immune response-mediated loss of
      transduced cells from the brain. Confocal analysis of these brains demonstrated
      physical contacts between transduced brain cells and CD19+ cells. To test the
      hypothesis that B cells play a causal role in the loss of infected cells from the
      brain, we demonstrated that animals devoid of B cells were unable to eliminate
      transgene expression at early time points after immunization. This demonstrates
      that B cells play a necessary role in the loss of transgene expression at early,
      but not late, time points postimmunization. Thus, these data have important
      implications for our understanding of the role of B cells as immune effectors
      during the immune-mediated clearance of viral infections from the CNS, and also
      for understanding mechanisms operating in brain autoimmunity, as well as for the
      potential safety of clinical gene therapy for brain diseases.

PMID- 16987069
TI  - Immunization of mice with a DNA vaccine based on severe acute respiratory
      syndrome coronavirus spike protein fragment 1.
AB  - According to data in GenBank, a gene encoding SARS spike protein fragment 1 (S1)
      was synthesized. After recombination with an immunostimulatory sequence (ISS),
      the gene was cloned into the plasmid pIRES to produce pIRES-ISS-S1. On
      confirmation of the expression of S1 protein by indirect immunofluorescence assay
      (IFA), after the transfection of pIRES-ISS-S1 into BHK-21 cells, the DNA vaccine
      was repeatedly administrated to BALB/c mice. CD4+ and CD8+ spleen T lymphocytes
      were analyzed by flow cytometry (FCM) to evaluate T cell-mediated immune
      responses, the antigen-specific responses of T cells were evaluated by cytotoxic
      T lymphocyte (CTL) assay, and the level of IgG in antisera from immunized mice
      was determined by enzyme-linked immunosorbent assay. Results showed that the
      counts of spleen CD4+ and CD8+ T lymphocytes were increased, that the T cell
      mediated immune responses showed antigen specificity, and that IgG was
      significantly induced with DNA vaccines pIRES-ISS-S1 and pIRES-S1 at titers of
      1:320 and 1:160, respectively. These results are promising for the protective
      immunization of humans.

PMID- 16987070
TI  - Efficacy of modified levamisole adjuvant on inactivated virus vaccine.
AB  - To improve efficacy, especially for the cell-mediated response to inactivated
      viral vaccines, a modified levamisole (LMS) adjuvant formulation, designated
      LMS+, was evaluated for its efficacy in mice and chickens, using Newcastle
      Disease Virus (NDV) as a model pathogen. Compared with oil adjuvant, the killed
      NDV in LMS+ induced a significantly higher helper T cell type 1 response, as
      shown by higher levels of interleukin-2, interferon-gamma, T cell proliferation,
      and delayed-type hypersensitivity responses, without sacrificing the level of IgG
      production in mice. In addition, vaccine in LMS+ formulation increased the
      expression of MHC and costimulatory molecules as well as the number of CD11c+
      dendritic cells, suggesting that the better response to the LMS+ formulation
      occurs partly via the maturation of dendritic cells and activation of MHC-antigen
      presentation and costimulation. Furthermore, this formulation provides 100%
      protection in chickens after challenge with a lethal dose of virulent NDV strain
      F48E9 at 1000 ELD50 (50% egg lethal dose). These results demonstrated that
      modified LMS+ adjuvant could be used to improve both humoral and cell-mediated
      responses for inactivated viral vaccines and its development as an effective
      inactivated viral vaccine is warranted.

PMID- 16987071
TI  - Gene expression contributing to recruitment of circulating cells in response to
      vesicular stomatitis virus infection of the CNS.
AB  - During acute Vesicular Stomatitis Virus (VSV) infection of the mouse central
      nervous system, neutrophils, natural killer (NK) cells, macrophages, and CD4+ and
      CD8+ T cells are recruited from the circulation in response to chemokines and
      cytokines. This study elucidated the production of these factors and infiltration
      of these peripheral cells. Chemokines that were observed included CCL1, CXCL10
      (IP-10), CCL5 (RANTES), CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CXCL1 (MIP-2), CCL2
      (MCP-1), and CCL11 (eotaxin). Cytokines produced in response to the infection
      include IL-1 and interferon-gamma, but not type I interferons. Neutrophils are
      the first recruited cell type, appearing as early as 24 h after intranasal
      application of the virus. NK cells follow, but T cells are not detected until 6
      days postinfection.

PMID- 16987072
TI  - Reovirus strain-dependent inflammatory cytokine responses and replication
      patterns in a human monocyte cell line.
AB  - Mammalian Orthoreoviruses are important models for studies of viral pathogenesis.
      In the rat lung, Reovirus strain type 3 Dearing (T3D) induces substantially more
      inflammation than does strain type 1 Lang (T1L). To better understand mechanisms
      underlying differences in the host inflammatory response elicited by T1L and T3D,
      we characterized cytokine expression patterns induced by those strains after
      infection of THP-1 monocyte cells. THP-1 cells were adsorbed with either viable
      or ultraviolet- inactivated T1L and T3D and assayed for mRNA and protein
      production of growth-regulated oncogene-alpha (GRO-alpha), interleukin-8 (IL-8),
      or tumor necrosis factor-alpha (TNF-alpha). T3D stimulated mRNA and protein
      production of all three cytokines, whereas T1L stimulated mRNA and protein
      production of IL-8 and TNF-alpha but not GRO-alpha. In each case, T3D induced
      greater cytokine mRNA and protein expression than did T1L. Nonviable virus did
      not stimulate detectable cytokine secretion, suggesting a requirement for viral
      RNA synthesis in cytokine induction by THP-1 cells. A greater percentage of THP-1
      cells was infected with T1L than T3D as assessed by infectious center assay, and
      T1L achieved higher yields of infectious progeny than did T3D in infected THP-1
      cells as determined by plaque assay. These strain-dependent differences in
      cytokine responses and corresponding replication patterns in monocyte cells
      parallel findings made in studies of rat models of pneumonia and provide clues
      about how Reovirus interfaces with the host innate immune response to produce
      pulmonary disease.

PMID- 16987073
TI  - Tumor necrosis factor-alpha genetic predisposing factors can influence clinical
      severity in nephropathia epidemica.
AB  - Severe human infection with Hantavirus is characterized by high fever, cold
      chills, thrombocytopenia, arterial hypotension, acute renal failure, and/or adult
      respiratory distress syndrome (ARDS)-like pulmonary involvement, but the clinical
      course varies greatly between individuals. We investigated whether genetically
      determined differences in tumor necrosis factor (TNF)-alpha production can
      influence the severity of Hantavirus disease. We studied a TNF-alpha single
      nucleotide promoter polymorphism (SNP) at position -238 (a guanine [G]-to-adenine
      [A] transition) and ex vivo TNF-alpha production in a recall study of 36 Belgian
      patients who had a serologically proven form of Puumala virus-induced Hantavirus
      infection with the kidney as main target organ. In our study, the highest
      creatinine levels were found in patients with the lowest ex vivo TNF-alpha
      production. Creatinine levels correlated inversely with TNF-alpha production (R =
      -0.35, p < 0.05). The number of thrombocytes was significantly lower in patients
      with the GA-238 genotype (low TNF-alpha producers) compared with patients with
      the GG-238 genotype. In our study, genetically determined low production of TNF
      alpha was associated with some parameters indicating a more severe clinical
      course of Puumala Hantavirus infection in humans, possibly by impaired activation
      of TNF-alpha-dependent antiviral mechanisms, which could in turn result in
      decreased clearance of Hantavirus.

PMID- 16987074
TI  - Levels of soluble vascular cell adhesion molecule-1 and soluble intercellular
      adhesion molecule-2 in plasma of patients with hemorrhagic fever with renal
      syndrome, and significance of the changes in level.
AB  - Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease
      characterized by endothelial dysfunction. Vascular cell adhesion molecule (VCAM)
      1 and intercellular adhesion molecule (ICAM)-2 provide costimulatory signals for
      the activation of T lymphocytes; these adhesion molecules play key roles in
      leukocyte adherence and propagation of inflammatory responses. They may be
      involved in the immunologic response that leads to vascular endothelial cell
      (VEC) and kidney damage of HFRS patients, and increased levels of soluble (s)VCAM
      1 and sICAM-2 in plasma may indicate the severity of HFRS. We examined the
      presence of sVCAM-1 and sICAM-2 in 52 plasma samples collected from 52 patients.
      We tested these plasma samples for sVCAM-1 and sICAM-2 by double-antibody
      sandwich ELISA. We found variable, but persistently elevated, levels of sVCAM-1
      and sICAM-2 throughout the various phases and types of the disease, which
      suggested sVCAM-1 may play an important role in the immunopathological lesions of
      HFRS and is closely correlated to the severity of HFRS and the degree of kidney
      damage. sICAM-2 may be associated with the hyperfunctioning of the cellular
      immune response.

PMID- 16987075
TI  - Concentrations of soluble Fas and soluble Fas ligand as indicators of programmed
      cell death among patients coinfected with Human Immunodeficiency Virus and
      Hepatitis C Virus.
AB  - Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) coinfections can
      affect mechanisms of programmed cell death and therefore influence acquired
      immunodeficiency syndrome (AIDS) development as well as the course of chronic
      hepatitis C. The aim of the study was to assess soluble Fas (sFas) and soluble
      Fas ligand (sFasL) concentrations in HIV- and HCV-coinfected patients and,
      moreover, to establish their relationships with HIV viral load, CD4+ T lymphocyte
      count, as well as liver function tests. Seventy-eight patients were included in
      the study, among them 30 coinfected with HIV and HCV, 10 infected only with HIV,
      and 38 infected only with HCV. HIV infection was confirmed by means of Western
      blot analysis; HIV viral load was measured by RTPCR; and CD3+, CD4+, and CD8+ T
      lymphocyte counts were established by means of flow cytometry. HCV infection was
      confirmed through HCV RNA isolation, using RT-PCR. sFas and sFasL concentrations
      were measured in duplicate by ELISA. The mean CD4+ T lymphocyte count decreased
      in HIV- and HCV-coinfected patients versus HIV-infected individuals (429 versus
      279/ml). sFasL protein was detectable principally in HIV-infected individuals
      without HCV infection (90%), whereas in those with HCV infection it occurred only
      in 11% of cases. The highest sFas concentration was observed in HCV-infected
      patients (25.9 ng/ml) as well as in HIV- and HCV-coinfected individuals (20.3
      ng/ml). This concentration was negatively proportional to sFasL prevalence. The
      results of our study suggest that HCV infection in HIV-positive individuals may
      suppress processes of programmed cell death. There was no correlation between
      sFas, sFasL, and HIV-1 viral load. On the other hand, sFas concentration and the
      presence of sFasL were related to CD4+ T lymphocyte count.

PMID- 16987076
TI  - Expression of human CD226 on T cells and natural killer cells and of soluble
      CD226 in plasma of HIV-1-infected Chinese patients.
AB  - Our objective was to detect the expression of CD226 on natural killer (NK) cells
      and T cells, and to measure the amount of soluble CD226 in the plasma of HIV
      infected individuals, in order to evaluate the function of CD226 in HIV
      infection. Thirty-four untreated HIV-1-infected patients and 26 normal controls
      were enrolled and three-color flow cytometry was used to detect the expression of
      CD226 on T lymphocytes and NK cells in whole blood samples taken from the
      patients and normal controls, and in HIV-1SF33-infected peripheral blood
      mononuclear cells (PBMCs). An enzymelinked immunosorbent assay (ELISA) was used
      to detect the level of soluble CD226 in the plasma of HIV-infected patients and
      normal controls and in the supernatant of HIV-1SF33-infected cells. The level of
      CD226 expression on CD3+, CD4+, and CD8+ T cells and on CD3- CD16+ NK cells of
      HIV-infected patients was significantly higher than that of normal controls (p <
      0.01). The level of soluble CD226 in the plasma of HIV-infected patients was also
      significantly higher than that of normal controls (p < 0.01). After stimulation
      with HIV-1SF33, the level of CD226 expression on CD3+ T cells and CD3- CD16+ NK
      cells of cultured PBMCs reached peak values at 48 h, which was earlier than in
      uninfected control cells (72 h). The level of soluble CD226 in the supernatant of
      HIV- 1SF33-infected cell culture was higher than that of uninfected cells, and
      the level of soluble CD226 in the supernatant of HIV-1SF33-infected cells reached
      the peak value at 72 h, which was earlier than in uninfected control cells (96 h)
      but later than the time of peak CD226 expression on CD3+ T lymphocytes (48 h). We
      conclude that CD226 may be involved in the immune response to HIV infection and
      that further experiments are needed to find the function of CD226 in the
      pathogenesis of HIV infection.

PMID- 16987078
TI  - Keystone conference on viral immunity: from basic mechanisms to vaccines (X7) and
      advances in influenza research: from birds to bench to bedside (X8) Steamboat
      Springs, Colorado March 28-April 2, 2006.

PMID- 16987079
TI  - New reagents on the horizon for immune tolerance.
AB  - Recent advances in immunology and a growing arsenal of new drugs are bringing the
      focus of tolerance research from animal models into the clinical setting. The
      conceptual framework for therapeutic tolerance induction has shifted from a
      "sledgehammer" approach that relies solely on cellular depletion and cytokine
      targeting, to a strategy directed toward restoring a functional balance across
      the immune system, namely the different populations of naive cells, effector and
      memory cells, and regulatory cells. Unlocking the key to tolerance induction in
      the future will likely depend on our ability to harness the functions of T
      regulatory cells. Also, dendritic cells are strategically positioned at the
      interface between innate and adaptive immunity and may be subject to deliberate
      medical intervention in a way that can control a chronic inflammatory response.
      Many reagents with tolerance-inducing potential are currently undergoing clinical
      testing in transplantation, autoimmune diseases, and allergic diseases, and even
      more that are on the horizon promise to offer enormous benefits to human health.

PMID- 16987080
TI  - Cardiac resynchronization treatment of heart failure.
AB  - Cardiac resynchronization therapy (CRT) is well established as a treatment for
      patients with moderate to severe heart failure on optimal medical therapy. Early
      studies demonstrated improved functional capacity and evidence of reverse
      remodeling; more recently, CRT has been associated with a survival benefit in
      advanced heart failure both with and without a defibrillator. We review the eight
      landmark trials in CRT. To date, criteria have focused on electrical delay, but
      echocardiographic parameters emphasize the importance of mechanical delay or
      ventricular dyssynchrony. With the exponential rise in implants, new issues have
      emerged, such as optimal device programming, identifying appropriate candidates,
      and accounting for cases without clinical benefit from CRT.

PMID- 16987081
TI  - Advances in the treatment of prostate cancer.
AB  - Several recent advances have been made in the management of prostate cancer.
      Active surveillance is an increasingly attractive and reasonable approach for
      those with low-volume, low-risk disease. For locally advanced or localized high
      risk disease, neoadjuvant and adjuvant therapies are emerging as the standard of
      care. Innovative uses of traditional hormonal treatments can potentially limit
      common side effects. Recent data also support the utility of second-line hormonal
      therapy. For the first time, a survival advantage with the use of chemotherapy
      has been established. Much work is under way to augment its efficacy with novel
      agents such as targeted therapeutics and tumor vaccines. Recent scientific
      breakthroughs suggest additional strategies in treating prostate cancer.

PMID- 16987082
TI  - Rethinking electronic health records to better achieve quality and safety goals.
AB  - Health care information technology changes the ecosystem of a practice. Human
      roles, process work flow, and technology infrastructure are tightly interrelated.
      Medical errors may increase if a change in one is not accommodated by a change in
      the others. Introduction of information technology should be approached as an
      iterative process of care improvement rather than as a one-time insertion of an
      information system into established practice. Information technology supports a
      family of technological approaches, each with distinct mechanisms of action,
      benefits, and side effects. By matching technological approach to task and
      staging introduction into practice, initial benefit can be obtained more quickly,
      at reduced cost, while managing risk of a misfit. A staged approach to turning
      direct access by patients to their health information into more effective care is
      presented as an example of this strategy.

PMID- 16987083
TI  - Inflammatory bowel disease genetics: Nod2.
AB  - The inflammatory bowel diseases (IBD) are comprised of two major subphenotypes,
      Crohn's disease (CD) and ulcerative colitis (UC). A significant role for genetic
      factors in IBD was established from epidemiologic studies and, more recently, the
      identification of well-established disease associations, notably the association
      of Nod2 (CARD15) polymorphisms with CD. The mapping to CD of Nod2 variants that
      alter protein function represents one of the earliest, most well-established,
      associations in complex genetic disorders. Since the initial discovery, genotype
      phenotype correlations, definition of Nod2 expression and signaling pathways,
      association studies in other, related disorders, and features of Nod2 deficiency
      in murine models have been reported. Taken together, the Nod2 association to CD
      provides an illustrative model of the role of single gene variants in disease
      pathogenesis for common, complex multigenic disorders. Here we review general
      aspects of IBD genetics with particular focus on the role of Nod2 in CD.

PMID- 16987085
TI  - The diffusion of effective behavioral interventions project: development,
      implementation, and lessons learned.
AB  - Implementation of evidence-based HIV/STD prevention interventions can play an
      important role in reducing HIV and sexually transmitted diseases. This article
      describes the development, implementation, and lessons learned of the Diffusion
      of Effective Behavioral Interventions (DEBI) project, a strategy funded by the
      Centers for Disease Control and Prevention to diffuse evidence-based, group- and
      community-level HIV/STD prevention interventions to health departments and
      community-based organizations nationwide. The article specifically provides an
      overview of the rationale, description, and theoretical foundation of the
      project; a review of marketing efforts, including assessment of interests, needs,
      and capacities relative to the project; a description of project products, their
      purpose, approach employed to develop them, and their use by implementers; a
      description of the project's training coordination functions and activities;
      technical assistance issues; an overview of process and outcome evaluation
      components; new developments in response to feedback; and a discussion of future
      directions for DEBI. Project successes and challenges are addressed to inform
      future efforts to diffuse prevention interventions.

PMID- 16987086
TI  - Evidence-based HIV behavioral prevention from the perspective of the CDC's
      HIV/AIDS Prevention Research Synthesis Team.
AB  - The evidence-based approach to health promotion and disease prevention is growing
      in many public health sectors, including HIV behavioral prevention. This approach
      is based on utilizing relevant and rigorous scientific evidence, most
      appropriately identified through a systematic research synthesis process. With
      regard to HIV behavioral prevention, this research synthesis process provides
      decision makers and prevention planners with the evidence base and
      recommendations they need to translate proven scientific research into practice.
      The Center for Disease Control and Prevention's HIV/AIDS Prevention Research
      Synthesis Team conducts such research synthesis activities to help improve HIV
      behavioral prevention efforts. The team's recent systematic review of the
      literature during 2000 to 2004 identified HIV behavioral interventions with the
      best scientific evidence of efficacy, called best-evidence behavioral
      interventions. Challenges still exist, however, for determining which of these
      interventions should be disseminated and implemented. Once translated into
      practice, if these best-evidence behavioral interventions are further evaluated
      for effectiveness, these findings and, perhaps, the synthesis of such findings
      can be used to further improve HIV behavioral prevention in the field.

PMID- 16987087
TI  - Assessing community needs and agency capacity--an integral part of implementing
      effective evidence-based interventions.
AB  - Community-based organizations and public health departments have historically
      applied for and received funding to implement a variety of HIV prevention
      interventions, but it is unclear how they make decisions regarding which
      interventions to implement or whether their agency has sufficient capacity and/or
      resources to effectively carry them out. Assessment activities can play a
      valuable role in helping agencies make these decisions by providing information
      to better target services. Recent funding efforts supporting the Diffusion of
      Effective Behavioral Interventions Project and other evidence-based approaches
      for HIV prevention require that agencies possess basic skills to effectively
      conduct individual-, group-, or community-level interventions, as well as the
      specific activities associated with an evidence-based intervention (EBI). We
      examine the link among community assessment, agency capacity, and intervention
      effectiveness, and provide resources to better guide programs in assessing their
      communities and organizations in order to implement the most effective EBI.

PMID- 16987088
TI  - Preparing effective behavioral interventions to be used by prevention providers:
      the role of researchers during HIV Prevention Research Trials.
AB  - The likelihood of prevention providers and consumers adopting and implementing
      evidence-based HIV prevention interventions depends on the strategies employed in
      translating, packaging, and disseminating the findings from research to practice.
      Lessons from the Centers for Disease Control and Prevention's Replicating
      Effective Programs project have shown that to smoothly transfer HIV prevention
      technology from research to practice, researchers need to prepare for possible
      transfer during research trials. Preparation should include documenting details
      of the intervention beyond what is published in journals, including important
      details regarding what the intervention was about, how preparations for it were
      made, and how it was delivered. Researchers should also ensure that all relevant
      stakeholders are integrally involved in all aspects of the research and
      technology transfer process. Such collaborations encourage exchange of ideas and
      can make certain that interventions are designed to be relevant and acceptable to
      community agencies and feasible for them to implement.

PMID- 16987089
TI  - Adapting evidence-based behavioral interventions for new settings and target
      populations.
AB  - Many HIV prevention funding agencies require the use of evidence-based behavioral
      interventions (EBIs) previously shown to be effective through rigorous outcome
      evaluation. Often, the implementing agency's setting or target population is
      different than those in the original implementation and evaluation. The Centers
      for Disease Control and Prevention Division of HIV/AIDS Prevention, in
      collaboration with internal and external partners, developed draft guidance to
      adapt an EBI to fit the cultural context, risk determinants, risk behaviors, and
      unique circumstances of the agency without competing with or contradicting the
      core elements and internal logic. The guidance described in this article provides
      a systematic approach to help agencies identify the most appropriate intervention
      for their target population and agency capacity, monitor the process, and
      evaluate the outcomes of the adapted intervention. This guidance, currently being
      piloted with five community-based organizations, will be revised and disseminated
      at the conclusion of project activities.

PMID- 16987090
TI  - The Program Evaluation and Monitoring System: a key source of data for monitoring
      evidence-based HIV prevention program processes and outcomes.
AB  - The Centers for Disease Control and Prevention (CDC) Division of HIV/AIDS
      Prevention (DHAP) has responded to the need for accurate and timely data to
      monitor and evaluate federally funded HIV prevention programs by designing and
      implementing the Program Evaluation and Monitoring System (PEMS). PEMS is a
      national data reporting system that includes a standardized set of HIV prevention
      data variables, Web-based software for data entry and management, data collection
      and evaluation guidance and training, and software implementation support
      services. This article discusses the purposes of evaluation and the need for and
      development of PEMS and also describes how PEMS strengthens the monitoring and
      evaluation of HIV prevention services nationally and program planning,
      management, and monitoring locally. PEMS data may be used by prevention
      stakeholders at all levels to examine program fidelity, adaptation and tailoring,
      and key program health service utilization and behavioral outcomes. PEMS provides
      a strong foundation to bring a program closer to its intended goals and to serve
      the needs of the clients and the community, provides a means for agencies to
      fulfill their reporting mandates and funding obligations, and enables the CDC to
      monitor HIV prevention efforts in a consistent, efficient, and effective manner
      across the United States.

PMID- 16987091
TI  - Utilizing multilevel partnerships to build the capacity of community-based
      organizations to implement effective HIV prevention interventions in Michigan.
AB  - The Michigan Department of Community Health (MDCH), utilizing the expertise of
      public and private, federal, state, and local partners, increased the proportion
      of state health department-funded community-based organizations implementing
      effective behavioral interventions (EBIs) from .05 (1:18) in 2002 to .78 (14:18)
      in 2004. As the stewards of nearly two thirds of the HIV prevention funds awarded
      annually by the Centers for Disease Control and Prevention, state health
      departments occupy an important position in diffusing the science of EBIs to
      their grantees. This article describes the strategies and partners employed by
      Michigan's state health department to build the capacity of community-based
      providers to implement effective behavioral interventions. Additionally, lessons
      learned by the MDCH are highlighted and challenges to the long-term
      sustainability of these interventions are also discussed.

PMID- 16987092
TI  - Diffusion of effective HIV prevention interventions--lessons from Maryland and
      Massachusetts.
AB  - This article describes, compares, and contrasts the contexts, processes, and
      results of the experiences of Maryland and Massachusetts in diffusing evidence
      based interventions. The evolution of first Maryland's, then Massachusetts's,
      diffusion of effective interventions is described. Both states have extensive
      experience planning, developing and evaluating individual-, group-, and community
      level interventions promoted in the Centers for Disease Control and Prevention's
      Diffusion of Effective Behavioral Interventions (DEBI) initiative, as well as
      overcoming many barriers to translate research to practice. This article
      describes the processes whereby effective interventions were diffused from the
      planning to evaluation stages. This includes the role of community-planning
      groups and other local stakeholders in planning, procurement methods, and
      capacity building approaches. Specific milestones in increasing the evidence
      basis of program implementation, management, and evaluation are presented. For
      jurisdictions considering implementing DEBI, the article illustrates core
      programmatic and infrastructure capacities at the state and vendor level
      important to success in Maryland and Massachusetts. It also describes how each
      state's approach to the management and evaluation of prevention programs
      contributed to the effective diffusion of the behavioral interventions. Finally,
      this article provides recommendations about remaining gaps in evidence-based
      interventions to meet "real-world prevention needs" and ways to improve
      prevention targeting and effectiveness. This article recommends strategies to
      improve the dissemination of DEBI and other evidence-based interventions
      nationally.

PMID- 16987093
TI  - Adaptation and implementation of an evidence-based prevention counseling
      intervention in Texas.
AB  - HIV prevention counseling linked with testing has been shown to reduce high-risk
      behaviors and new sexually transmitted diseases in public clinic settings.
      However, few studies have been conducted evaluating the implementation of such
      models outside a research setting. This study sought to determine the extent to
      which the introduction of a standard protocol based on Project RESPECT improves
      the achievement of HIV prevention counseling goals of existing counseling and
      testing programs. Four prevention counseling programs contracting with the Texas
      Department of State Health Services completed a standardized 5-day training and
      implemented the protocols, counseling tools, and quality assurance (QA)
      procedures developed for the project. Introduction of the protocol was
      accomplished with existing program resources and significantly improved
      prevention counseling. Direct observation of counseling sessions demonstrated a
      significant improvement in attainment for eight of the nine counseling goals of
      initial sessions and for all counseling goals of follow-up sessions after the
      protocol was introduced. Client exit questionnaires reinforced this finding.
      Significant improvement was also found in use of counseling skills, with
      improvements in 6 of 10 skills observed in initial sessions and 4 of 10 skills in
      follow-up sessions. Challenges identified through semistructured interviews with
      counselors and supervisors included serving non-English-speaking and low-risk
      clients, mastery of the protocol, the amount of time required for QA, and
      implementation in settings with severe time constraints.

PMID- 16987094
TI  - Translating research into practice: the dissemination and initial implementation
      of an evidence-based HIV prevention program.
AB  - Substantial effort has gone into scientifically developing and evaluating HIV
      prevention interventions. These programs make only minor contributions to HIV
      prevention efforts until they are widely put into practice; however, little
      research has been conducted to study how evidence-based, community-level HIV
      prevention interventions diffuse from research into practice. This article
      explores how one such evidence-based intervention for young MSM, the Mpowerment
      Project (MP), is scaling up in the US. The goals of this article are threefold:
      (a) to describe our longitudinal study, currently underway, concerning issues
      regarding translating research to practice; (b) present detailed data from 69
      CBOs that are implementing the MP regarding characteristics of their communities,
      agencies, and target populations; and (c) to present baseline data on how these
      agencies are attempting to implement the MP, focusing on which intervention
      components CBOs decided to implement, modify, or delete and the implications of
      these modifications.

PMID- 16987095
TI  - Adapting the popular opinion leader intervention for Latino young migrant men who
      have sex with men.
AB  - Young Latino migrantmen who have sex with men are at high risk for HIV infection.
      The Popular Opinion Leader intervention, shown to be effective with White gay
      men, was adapted by the Farmworker Justice Fund, Inc., for this Latino migrant
      population. This project, called the Young Latino Promotores, was implemented
      over a 2-year period by community-based organizations in Vista, California, and
      McAllen, Texas, with capacity building assistance from the Farmworker Justice
      Fund, Inc. We report on challenges, preliminary findings, and lessons learned
      from adapting this intervention.

PMID- 16987096
TI  - Diffusing an HIV prevention intervention for African American Women: integrating
      afrocentric components into the SISTA Diffusion Strategy.
AB  - Although race and gender are not indicators for HIV/AIDS, both have
      disproportionately impacted African American women. African American women
      represent 13% of the U.S. female population and 67% of the AIDS cases among women
      (Fitzpatrick, The U.S. HIV/AIDS Epidemic in Women and Adolescent Females, HIV
      Prevention Conference, Atlanta, GA, 2005). The statistics underscore the need for
      targeted interventions that employ culturally relevant activities to enhance self
      esteem and communication skills while encouraging positive behavior change.
      Factors facilitating intervention effectiveness include culturally relevant
      components such as cultural practices, beliefs, values, norms, and ideologies
      (Janz et al., "Evaluation of 37 AIDS Projects," Health Education Quarterly,
      23(1), 80-97, 1996). HIV prevention programs targeting African American women
      should incorporate an approach that includes ethnic heritage as ameans to instill
      pride, therebymotivating positive behavior change and empowering women.
      Afrocentric approaches incorporate philosophies relevant to people of African
      descent and may be spiritually based. Coupling culturally relevant HIV prevention
      interventions with a culturally relevant diffusion strategy may enhance community
      receptiveness. The SISTA intervention (DiClemente & Wingood, "A Randomized
      Controlled Trial of an HIV Sexual Risk Reduction Intervention for Young African
      American Women," Journal of the American Medical Association, 274(16), 1271-1276,
      1995) incorporates both culturally and gender-relevant activities to empower
      African American women to make healthy life choices. The article presents the
      strategy used to nationally diffuse SISTA, which incorporated Afrocentric
      components within implementation delivery. Lessons learned demonstrate the
      significance of integrating additional Afrocentric and gender-relevant material
      to an existing intervention for African American women.

PMID- 16987097
TI  - Enhancing adoption of evidence-based HIV interventions: promotion of a suite of
      HIV prevention interventions for African American women.
AB  - The Centers for Disease Control and Prevention (CDC) currently promotes an HIV
      prevention intervention for young adult African American women, known as SISTA,
      through the Diffusion of Effective Behavioral Interventions (DEBI) program.
      Nationally, more than 700 agencies have completed a 1-week CDC-funded training to
      implement SISTA. Agencies that have been trained in SISTA are also eligible to
      receive training in a newly published HIV prevention intervention for African
      American adolescent females, known as SiHLE (Sistering, Informing, Healing,
      Living, and Empowering), as well as to receive training in a newly published
      prevention intervention for women living with HIV, known as WiLLOW (Women
      Involved in Life Learning From Other Women). All three of these HIV prevention
      interventions, target African American females, are designed to reduce HIV sexual
      risk behaviors and share similar theoretical, core, and methodological elements.
      The diffusion of innovation paradigm suggests that if potential adopters perceive
      one innovation as being closely related to another innovation, it may be useful
      to promote a cluster of innovations, rather than to treat each new innovation
      separately. This article examines how promotion of a suite of HIV interventions
      for African American females may facilitate adoption of the three evidence-based
      HIV interventions for this population.

PMID- 16987098
TI  - The VOICES/VOCES success story: effective strategies for training, technical
      assistance and community-based organization implementation.
AB  - The Centers for Disease Control and Prevention's Diffusion of Effective
      Behavioral Interventions (DEBI) project successfully disseminated VOICES/VOCES, a
      brief video-based HIV risk reduction intervention targeting African American and
      Latino heterosexual men and women at risk for HIV infection. Elements of the
      dissemination strategy included a comprehensive and user-friendly intervention
      kit, comprising (a) an implementationmanual and othermaterials necessary for
      conducting the intervention (b) a Training of Facilitators (TOF) curriculum used
      to teach agency staff how to implement the EBI in their setting, (c) a network of
      expert trainers who attend a training institute to become adept at using the TOF
      curriculum to train facilitators, (d) a comprehensive training coordination
      center to plan and deliver TOF trainings, (e) proactive technical assistance to
      trainers, and (f) post-TOF technical assistance for local implementers. This
      article reports on those strategies and a local CBO's successful participation in
      DEBI, resulting implementation of VOICES/VOCES, with unique approaches to
      adaptation and tailoring.

PMID- 16987099
TI  - An empirical assessment of implementation, adaptation, and tailoring: the
      evaluation of CDC's National Diffusion of VOICES/VOCES.
AB  - The Centers for Disease Control and Prevention (CDC), through its Diffusion of
      Effective Behavioral Interventions (DEBI) program, trained over 260 agencies on
      VOICES/VOCES between August 2003 and April 2005. ORC Macro conducted interviews
      with agency staff 3 months after receiving VOICES/VOCES training. This article
      discusses the diffusion of VOICES/VOCES; agencies' adoption, adaptation, and
      implementation of this intervention; and needs for ongoing proactive technical
      assistance (TA) for agencies to successfully integrate behavioral interventions
      into their programs. The vastmajority of agencies implemented VOICES/VOCES with
      fidelity to the core elements, and agencies successfully adapted the intervention
      to make it more appealing to target populations. TA is needed for interventions
      to be successfully adapted and implemented with fidelity to the core elements,
      and to ensure program sustainability. More effective interventions of short
      duration and minimum complexity to easily match with existing resources and
      conditions of agency capacity among HIV prevention providers in the community are
      needed.

PMID- 16987101
TI  - Yeast sphingolipids do not need to contain very long chain fatty acids.
AB  - Synthesis of VLCFAs (very long chain fatty acids) and biosynthesis of DHS
      (dihydrosphingosine) both are of vital importance for Saccharomyces cerevisiae.
      The bulk of VLCFAs and DHS are used for ceramide synthesis by the Lag1p
      (longevity-assurance gene 1)/Lac1p (longevity-assurance gene cognate 1)/Lip1p
      (Lag1p/Lac1p interacting protein) ceramide synthase. LAG1 and LAC1 are redundant
      but LIP1 is essential. Here we show that 4Delta
      (lag1Deltalac1Deltaypc1Deltaydc1Delta) cells devoid of all known endogenous
      ceramide synthesis pathways are unviable but can be rescued by the expression of
      Lass5, a mouse LAG1 homologue. Ceramide synthase activity of 4Delta.Lass5 cells
      only utilizes C16 and C18 fatty acids and does not require the help of Lip1p, an
      essential cofactor of Lag1p/Lac1p. HPLC-electrospray ionization-MS/MS analysis
      demonstrated that in IPCs (inositolphosphorylceramides) of 4Delta.Lass5, the very
      long chain fatty acids (C26 and C24) account for <1% instead of the normal >97%.
      Notwithstanding, IPCs incorporated into glycosylphosphatidylinositol anchors of
      4Delta.Lass5 show normal mobility on TLC and the ceramide- and raft-dependent
      traffic of Gas1p (glycophospholipid-anchored surface protein) from endoplasmic
      reticulum to Golgi remains almost normal. Moreover, the biosynthesis of C24:0
      fatty acids remains essential. Thus, C(24:0) and dihydrosphingosine are both
      necessary for survival of yeast cells even if they utilize C16 and C18 fatty
      acids for sphingolipid biosynthesis.

PMID- 16987102
TI  - Brachial artery diameter and vasodilator response to nitroglycerine, but not flow
      mediated dilatation, are associated with the presence and quantity of coronary
      artery calcium in asymptomatic adults.
AB  - In the present study, we investigated whether measures of brachial artery
      reactivity were associated with the presence and extent of subclinical coronary
      atherosclerosis in asymptomatic adults. Electron beam computed tomography was
      employed to assess the presence and quantity of CAC (coronary artery calcium) in
      441 participants (mean age, 61 years; 49% men) without prior history of CHD
      (coronary heart disease) or stroke, and CAC score was calculated using the method
      described by Agatston and co-workers [(1990) J. Am. Coll. Cardiol. 15, 827-832]
      High-resolution ultrasound was employed to measure BAD (brachial artery
      diameter), FMD (flow-mediated dilatation) and NMD (nitroglycerine-mediated
      dilatation). CAC score and FMD were log-transformed after adding 1 to reduce
      skewness. Multivariable logistic and linear regression models based on
      generalized estimating equations were used to assess whether BAD, FMD and NMD
      were each independently associated with the presence and quantity of CAC after
      adjustment for CHD risk factors and use of statin and hypertension medication.
      CAC was detectable in 64% of participants. After adjustment for age and sex, FMD
      was not correlated (r=-0.06; P=0.27), BAD was positively correlated (r=0.16;
      P=0.004) and NMD was inversely correlated in a borderline significant manner (r=
      0.10; P=0.084) with log(CAC+1). In multivariable logistic regression analyses,
      FMD was not associated, whereas higher BAD (P=0.021) and lower NMD (P=0.030) were
      independently associated with the presence of CAC. In multivariable linear
      regression analyses, higher BAD (P=0.004) and lower NMD (P=0.016), but not FMD,
      were independently associated with log(CAC+1). We conclude that greater diameter
      of the brachial artery and lower vasodilator response to nitroglycerine, but not
      FMD, are associated with subclinical coronary atherosclerosis.

PMID- 16987103
TI  - Leg crossing with muscle tensing, a physical counter-manoeuvre to prevent
      syncope, enhances leg blood flow.
AB  - In patients with orthostatic intolerance, the mechanisms to maintain BP (blood
      pressure) fail. A physical counter-manoeuvre to postpone or even prevent
      orthostatic intolerance in these patients is leg crossing combined with muscle
      tensing. Although the central haemodynamic effects of physical counter-manoeuvres
      are well documented, not much is known about the peripheral haemodynamic events.
      Therefore the purpose of the present study was to examine the peripheral
      haemodynamic effects of leg crossing combined with muscle tensing during 70
      degrees head-up tilt. Healthy subjects (n=13) were monitored for 10 min in the
      supine position followed by 10 min in 70 degrees head-up tilt and, finally, for 2
      min of leg crossing with muscle tensing in 70 degrees head-up tilt. MAP (mean
      arterial BP), heart rate, stroke volume, cardiac output and total peripheral
      resistance were measured continuously by Portapres. Leg blood flow was measured
      using Doppler ultrasound. Leg vascular conductance was calculated as leg blood
      flow/MAP. A significant increase in MAP (13 mmHg), stroke volume (27%) and
      cardiac output (18%), a significant decrease in heart rate (-5 beats/min) and no
      change in total peripheral resistance during the physical counter-manoeuvre were
      observed when compared with baseline 70 degrees head-up tilt. A significant
      increase in leg blood flow (325 ml/min) and leg vascular conductance (2.9
      arbitrary units) were seen during the physical counter-manoeuvre when compared
      with baseline 70 degrees head-up tilt. In conclusion, the present study indicates
      that the physical counter-manoeuvre of leg crossing combined with muscle tensing
      clearly enhances leg blood flow and, at the same time, elevates MAP.

PMID- 16987104
TI  - The translation initiation factor eIF2beta is an interactor of protein
      phosphatase-1.
AB  - It is reasonably well understood how the initiation of translation is controlled
      by reversible phosphorylation of the eukaryotic translation initiation factors
      eIF2alpha, eIF2Bepsilon and eIF4E. Other initiation factors, including eIF2beta,
      are also established phosphoproteins but the physiological impact of their
      phosphorylation is not known. Using a sequence homology search we found that the
      central region of eIF2beta contains a putative PP1-(protein phosphatase-1)
      binding RVxF-motif. The predicted eIF2beta-PP1 interaction was confirmed by PP1
      binding and co-immunoprecipitation assays on cell lysates as well as with the
      purified components. Site-directed mutagenesis showed that eIF2beta contains, in
      addition to an RVxF-motif, at least one other PP1-binding site in its C-terminal
      half. eIF2beta functioned as an inhibitor for the dephosphorylation of glycogen
      phosphorylase and Ser51 of eIF2alpha by PP1, but did not affect the
      dephosphorylation of Ser464 of eIF2Bepsilon by this phosphatase. Strikingly,
      eIF2beta emerged as an activator of its own dephosphorylation (Ser2, Ser67,
      Ser218) by associated PP1, since the substrate quality of eIF2beta was decreased
      by the mere mutation of its RVxF-motif. These results make eIF2beta an attractive
      candidate substrate for associated PP1 in vivo. The overexpression of wild-type
      eIF2beta or eIF2beta with a mutated RVxF-motif did not differentially affect the
      rate of translation, indicating that the binding of PP1 is not rate-limiting for
      translation under basal conditions.

PMID- 16987105
TI  - The fructosamine 3-kinase knockout mouse: a tool for testing the glycation
      hypothesis of intracellular protein damage in diabetes and aging.
AB  - Protein glycation and the formation of AGEs (advanced glycation end-products) and
      cross-links have been hypothesized to play a role in the pathogenesis of age- and
      diabetes-related complications. The discovery that FN3K (fructosamine 3-kinase)
      results in protein deglycation upon phosphorylation of glucose-derived Amadori
      products suggests that intracellular glycation could be deleterious under certain
      circumstances. In order to approach the question of the biological relevance of
      intracellular glycation, in this issue of the Biochemical Journal, Veiga-da-Cunha
      and colleagues generated an FN3K-knockout mouse. The mice grow normally and are
      apparently healthy, and levels of protein-bound and free fructoselysine are
      elevated in several tissues of importance to diabetic complications. This
      commentary discusses the clinical and evolutionary significance of FN3K, and
      proposes experimental approaches for revealing the existence of a biological
      phenotype.

PMID- 16987106
TI  - Compatible solutes and fungal development.
AB  - Compatible solutes are components that can be quickly accumulated and degraded
      inside fungal cells. They do not disturb the functioning of proteins and protect
      the cell under adverse conditions. In this issue of the Biochemical Journal,
      Solomon and co-workers evaluate the role of mannitol, one of these components, in
      Stagonospora nodorum, a plant-pathogenic fungus, and find surprising effects on
      the development of spores and spore-forming structures.

PMID- 16987107
TI  - Intricacies and surprises of nuclear-mitochondrial co-evolution.
AB  - In this issue of the Biochemical Journal, Watanabe and colleagues disclose
      another fascinating facet of the mitochondrial protein synthesis machinery: one
      of the two nematode mitochondrial elongation factors Tu, EF-Tu1, specifically
      recognizes the D-arm of T-armless tRNAs via a 57-amino-acid C-terminal extension
      that compensates for the reduction in tRNA structure. This principle provides a
      paradigm for the evolutionary events thought to have ignited the transition from
      an ancient 'RNA world' to the 'protein world' of today.

PMID- 16987109
TI  - Does specialty board certification influence clinical outcomes?
AB  - BACKGROUND: The public seems to crave a simplistic index of 'quality', analogous
      to 'The Good Housekeeping Seal of Approval', for the complex endeavour of
      clinical medicine. The American Board of Medical Specialties (ABMS) and its
      member boards have purported to fill the vacuum in an effort that bears many of
      the earmarks of a public relations publicity campaign. The author examined the
      validity of the evidence touted in support of that effort. METHODS: By applying
      Hill's causal epidemiologic criteria and logical and statistical inference, the
      author evaluated: (i) published data sources consisting of the most comprehensive
      collection of studies yet gathered that purports to provide evidence of the
      relevance of board certification to clinical outcomes, a collection presented by
      Sharp et al. apparently with the advice and consent of ABMS, that they posited as
      containing 'relevant findings', to what purpose they left unspecified; and (ii)
      the review article of Sharp et al. RESULTS: The data that Sharp et al. presented
      provided no credible link between specialty board certification and outcomes or
      'quality' of clinical care. Sharp et al. ignored the evidence of absent evidence
      they found and proposed enthusiastic but unjustified conclusions in support of
      specialty board certification as an index of clinical 'expertise'. CONCLUSIONS:
      No evidence supports the touted clinical benefit of specialty board
      certification. Specialists in clinical medicine and surgery are unamenable to
      simplistic evaluation by examination, yet specialty board certification remains
      an ersatz standard of doctors' clinical quality in the absence of supporting
      evidence.

PMID- 16987108
TI  - Structure, function and mechanism of exocyclic DNA methyltransferases.
AB  - DNA MTases (methyltransferases) catalyse the transfer of methyl groups to DNA
      from AdoMet (S-adenosyl-L-methionine) producing AdoHcy (S-adenosyl-L
      homocysteine) and methylated DNA. The C5 and N4 positions of cytosine and N6
      position of adenine are the target sites for methylation. All three methylation
      patterns are found in prokaryotes, whereas cytosine at the C5 position is the
      only methylation reaction that is known to occur in eukaryotes. In general,
      MTases are two-domain proteins comprising one large and one small domain with the
      DNA-binding cleft located at the domain interface. The striking feature of all
      the structurally characterized DNA MTases is that they share a common core
      structure referred to as an 'AdoMet-dependent MTase fold'. DNA methylation has
      been reported to be essential for bacterial virulence, and it has been suggested
      that DNA adenine MTases (Dams) could be potential targets for both vaccines and
      antimicrobials. Drugs that block Dam could slow down bacterial growth and
      therefore drug-design initiatives could result in a whole new generation of
      antibiotics. The transfer of larger chemical entities in a MTase-catalysed
      reaction has been reported and this represents an interesting challenge for bio
      organic chemists. In general, amino MTases could therefore be used as delivery
      systems for fluorescent or other reporter groups on to DNA. This is one of the
      potential applications of DNA MTases towards developing non-radioactive DNA
      probes and these could have interesting applications in molecular biology. Being
      nucleotide-sequence-specific, DNA MTases provide excellent model systems for
      studies on protein-DNA interactions. The focus of this review is on the
      chemistry, enzymology and structural aspects of exocyclic amino MTases.

PMID- 16987110
TI  - Adolescent Drug Abuse Diagnosis (ADAD) vs. Health of Nation Outcome Scale for
      Children and Adolescents (HoNOSCA) in clinical outcome measurement.
AB  - BACKGROUND: The Adolescent Drug Abuse Diagnosis (ADAD) and Health of Nation
      Outcome Scales for Children and Adolescents (HoNOSCA) are both measures of
      outcome for adolescent mental health services. AIMS: To compare the ADAD with
      HoNOSCA; to examine their clinical usefulness. METHODS: Comparison of the ADAD
      and HoNOSCA outcome measures of 20 adolescents attending a psychiatric day care
      unit. RESULTS: ADAD change was positively correlated with HoNOSCA change. HoNOSCA
      assesses the clinic's day-care programme more positively than the ADAD. The ADAD
      detects a group for which the mean score remains unchanged whereas HoNOSCA does
      not. CONCLUSIONS: A good convergent validity emerges between the two assessment
      tools. The ADAD allows an evidence-based assessment and generally enables a
      better subject discrimination than HoNOSCA. HoNOSCA gives a less refined
      evaluation but is more economic in time and possibly more sensitive to change.
      Both assessment tools give useful information and enabled the Day-care Unit for
      Adolescents to rethink the process of care and of outcome, which benefited both
      the institution and the patients.

PMID- 16987111
TI  - Measuring physiotherapists' guideline adherence by means of clinical vignettes: a
      validation study.
AB  - RATIONALE, AIMS AND OBJECTIVES: To assess the criterion validity of paper-and
      pencil vignettes to assess guideline adherence by physiotherapists in the
      Netherlands. The evidence-based physiotherapy practice guideline for low back
      pain was used as an example. METHODS: Four vignettes were constructed and pre
      tested. Three vignettes were found to represent an adequate case-mix. They
      described one patient with specific low back pain, one with non-specific low back
      pain and a normal recovery process and one with non-specific low back pain and a
      delay in the recovery process. Invited to participate were 113 primary care
      physiotherapists who had joined an randomized controlled trial study 8 months
      before, in which guideline adherence had been measured by means of semi
      structured treatment recording forms. The criterion validity was determined with
      Spearman's r(s), using Cohen's classification for the behavioural sciences to
      categorize its effect size. RESULTS: Of the 72 physiotherapists who agreed to
      participate, 39 completed the questions on the vignettes. In the end, both
      adherence measures were available for 34 participants, providing 102 vignettes
      and 268 recording forms. Mean guideline adherence scores were 57% (SD = 17) when
      measured by vignettes and 74% (SD = 15) when measured by recording forms.
      Spearman's r(s) was 0.31 (P = 0.036), which, according to Cohen's classification,
      is a medium effect size. CONCLUSION: Vignettes are of acceptable validity, and
      are an inexpensive and manageable instrument to measure guideline adherence among
      large groups of physiotherapists. Further validation studies could benefit from
      the use of standardized patients as a gold standard, a more diverse case mix to
      better reflect real physiotherapy practice, and the inclusion of longitudinal
      vignettes that cover the patients' course of treatment.

PMID- 16987112
TI  - Preliminary development of the new individualized HDQoL questionnaire measuring
      quality of life in adult hypopituitarism.
AB  - OBJECTIVES: The objectives were (1) to report the preliminary development of the
      Hormone Deficiency-dependent Quality of Life (HDQoL) questionnaire, a new
      individualized questionnaire in which respondents rate personally applicable
      domains for importance and impact of hormonal deficiency and its treatment; (2)
      to evaluate the HDQoL's psychometric properties for adults with hypopituitarism
      including growth hormone deficiency (GHD). METHODS: Internal consistency
      reliability, aspects of validity, and sensitivity to change of the HDQoL were
      investigated in: (1) a cross-sectional survey of 157 adults with treated or
      untreated GHD; (2) a randomized, placebo-controlled study of 3 months' growth
      hormone (GH) withdrawal from 12 of 21 GH-treated adults. RESULTS: Thirteen of the
      original 18 HDQoL domains were relevant and important for GH-deficient adults.
      The shorter 13-item HDQoL had excellent internal reliability (Cronbach's alpha
      coefficient = 0.914, n = 109), and was sensitive to sex differences (cross
      sectional study): women perceived worse present QoL than men [t(149.8) = 2.33, P
      = 0.021]. The HDQoL was sensitive to change (GH-withdrawal study) with a
      significant between-group difference in change in domain scores for things I can
      do physically[t(16) = 2.47, P = 0.025, 2-tailed], patients withdrawn from GH
      reporting greater negative impact of hormone deficiency on this domain at end
      point. Qualitative work resulted in the addition of seven new HDQoL domains,
      including energy and bodily pain. CONCLUSION: The HDQoL, although at an early
      stage of development, proved useful in identifying expected changes following GH
      withdrawal. The extended 20-item version is recommended for further evaluation in
      assessing the impact of hypopituitarism on QoL.

PMID- 16987113
TI  - Preventing paediatric admissions for respiratory disease: a qualitative analysis
      of the views of health care professionals.
AB  - RATIONALE: The number of emergency paediatric admissions is increasing each year.
      The reasons for this are unclear but may include increasing demand from parents,
      changes in GP working patterns, and an increase in unnecessary admissions.
      Respiratory disease is the commonest diagnostic category for emergency admission
      in childhood. AIMS: To generate hypotheses for reduction in unnecessary
      admissions for respiratory disease by qualitative analysis of the views of health
      care professionals, to determine the proportion of preventable admissions as
      perceived by clinicians, and to assess the modified Paediatric Appropriateness
      Evaluation Protocol against clinicians judgements of appropriateness of
      admission. DESIGN: Eight health care professionals analysed clinical data from
      primary and secondary care for 94 cases that were admitted to an emergency
      assessment unit and received a hospital discharge diagnosis of respiratory
      disease. They assessed whether each admission was appropriate, whether it was
      preventable, and how it might have been prevented. RESULTS: A total of 31% of
      cases admitted to the assessment unit (29/94) were classified as preventable by
      the majority of professionals assessing the case. Provision of additional
      support, monitoring, and observation in the community was cited as a means of
      prevention in 33/94 cases. There was poor agreement between the modified PAEP and
      clinicians' assessments of appropriateness of admission (kappa 0.1). CONCLUSIONS:
      If the agreed views of these experienced doctors and nurses are correct,
      provision of additional services in the community could be an important means of
      preventing emergency admissions for respiratory disease. This hypothesis should
      be tested by further research including the views of families. The study provides
      further evidence that the modified PAEP may not be valid for use in UK practice.
      If inappropriate admission rates are to be used to measure effectiveness of
      services we need to develop an objective measure of appropriateness valid for use
      in the UK.

PMID- 16987114
TI  - A community model of group therapy for the older patients with chronic
      obstructive pulmonary disease: a pilot study.
AB  - OBJECTIVE: A community-based programme for chronic obstructive pulmonary disease
      (COPD) patients in group sessions is designed, and the feasibility, acceptability
      and physical and psychosocial outcomes evaluated. METHODS: Patients with COPD
      discharged from hospital, or those attending specialist outpatient clinic, with a
      history of hospital admission owing to COPD in the preceding 12 months were
      recruited. Those who had malignancy or were housebound were excluded. Group
      sessions were arranged once a week in a Community Centre, and consisted of two
      hourly sessions. The components of each session consist of education regarding
      the disease, breathing techniques, use of oxygen and other medication, smoking
      cessation, nutrition, dyspnoea management skills, relaxation and energy
      conservation techniques, introduction of social and community support, and
      strengthening as well as aerobic exercises. Assessments before and after
      intervention include lung function, 6 minutes walk test (6MWT), general Health
      Questionnaire (GHQ), the St. George's Respiratory Questionnaire (SGRQ), and a
      COPD knowledge Questionnaire. A programme evaluation was carried out using
      questionnaire and group discussions. RESULTS: Forty-four subjects were recruited,
      with 75% completing the programme, and 20% with drawing for unavoidable reasons.
      Statistically significant improvement was noted in all domains of the GHQ, SGRQ,
      and knowledge test, while the mean 6MWT improved, although statistical
      significance was not reached. Subjects were enthusiastic about the provision of
      this service in helping them cope with the disease through empowerment and mutual
      support. CONCLUSION: A group community intervention programme for COPD patients
      is feasible and acceptable, with positive psychosocial outcomes. Such a model
      could be further developed and cost-effectiveness evaluated as a model of chronic
      disease management in the community.

PMID- 16987115
TI  - The comparison of different dyspnoea scales in patients with COPD.
AB  - OBJECTIVES: (i) To compare the relationship between different dyspnoea scales and
      physical and clinical parameters of patients with chronic obstructive pulmonary
      disease (COPD); and (ii) to determine the most suitable scale among these scales
      for this patient group. METHODS: Forty patients with COPD [mean 1st second forced
      expiratory volume (FEV(1)), 49.16 +/- 2.33% predicted], aged 53-85 participated
      in this study. The severity of dyspnoea was assessed with different five scales
      [Modified Borg Scale (MBS), Visual Analogue Scale (VAS), Medical Research Council
      Dyspnoea Scale (MRCS), Baseline Dyspnoea Index (BDI) and Oxygen Cost Diagram
      (OCD)]. As clinical parameters, respiratory function was measured by means of
      pulmonary function test and arterial blood gas analysis. As physical parameters,
      age and body mass index was recorded. RESULTS: Patient's dyspnoea severities were
      1.59 +/- 2.75, 2.03 +/- 2.82, 2.14 +/- 1.44, 6.81 +/- 4.07, 4.56 +/- 2.47 for
      MBS, VAS, MRCS, BDI, OCD, respectively (P = 0.08). It was proven that only
      %FEV(1) had a correlation with MRCS (r = -0.67, P = 0.01) and BDI (r = 0.58, P =
      0.02). In addition to these determinations MRCS, MBS and VAS had a strong
      correlation defining their relationships with each other (P < 0.05). CONCLUSIONS:
      MRCS and BDI could assess dyspnoea during daily activities, so these scales
      showed strength correlation with physical and clinical values. Briefly MRCS is
      the most suitable dyspnoea scale for the patients with COPD, moreover, BDI, as
      the second suitable scale, is correlated only with MRCS. Based on these findings,
      we recommended that MRCS and BDI are appropriate scales for evaluation of
      dyspnoea in the patients with COPD.

PMID- 16987116
TI  - Review and evaluation of the Dutch guidelines for osteoporosis.
AB  - RATIONALE: At the request of a Dutch governmental organization, a
      multidisciplinary group of osteoporosis experts in the Netherlands published in
      2002 a guideline on case finding, diagnosis, prevention and treatment of
      osteoporosis. These guidelines were evaluated for their validity and
      applicability. METHODS: Analysis by 5 external osteoporosis experts using the
      'Appraisal of Guidelines for Research & Evaluation' ('AGREE') instrument.
      RESULTS: The score for the 6 domains of AGREE was 88% for the scope and purpose
      domain, 76% for stakeholder involvement, 81% for rigour of development, 84% for
      clarity and presentation, 77% for applicability and 73% for editorial
      independence. For single components of the domains of AGREE, highest scores were
      found for systematic methods used to search for evidence (100%), inclusion of
      individuals from all the relevant professional groups (95%) and ease of
      identifying key recommendations (95%). Lowest scores to single components of the
      several domains were given for piloting among target users (44%). All experts
      recommended the guidelines for use in practice. CONCLUSIONS: The AGREE instrument
      scored high for development, clarity and presentation but low for piloting among
      target users and implementation. Based on the guideline, algorithms from case
      finding to treatment were constructed that could be tested for piloting among
      target users and for implementation of the guideline.

PMID- 16987117
TI  - Use of a multidimensional assessment tool in a psychiatric adolescent care unit.
AB  - AIMS: Adolescent mental health problems require treatment and care that are
      adapted to their needs. To evaluate this issue, it was decided to implement a
      multidimensional instrument focused on a global approach to adolescent social and
      behavioural functioning, combined with the ICD-10 classification. METHODS: The
      combination of an assessment interview and a classification tool enabled the
      method to integrate the measurement of several domains of patient-based outcome
      rather than focus on the measurement of symptoms. A group of 68 adolescents from
      an inpatient unit were compared with 67 adolescents from the general population.
      RESULTS: Results suggest that adolescents from the care unit adopt significantly
      riskier behaviour compared with adolescents from the control group. As expected,
      the main problems identified refer to the psychological and familial areas. A
      cluster analysis was performed and provided three different profiles: a group
      with externalizing disorders and two groups with internalizing disorders. On the
      basis of a structured interview it was possible to obtain information in a
      systematic way about the adolescents' trajectory (delinquency, physical and
      sexual abuse, psychoactive substance use). CONCLUSION: It was shown that
      treatment and care should not focus exclusively on mental health symptoms, but
      also upon physical, psychological and social aspects of the adolescent. A global
      approach helps in the consideration of the multitude of factors which must be
      taken into account when working with people with serious mental health problems
      and may help to turn the care unit's activity more specifically towards the needs
      of these adolescents.

PMID- 16987118
TI  - Impact of patient-reported outcome measures on routine practice: a structured
      review.
AB  - RATIONALE, AIMS AND OBJECTIVES: Regular use of patient-reported outcome measures
      (PROMs) by health care providers in their routine practice may help to improve
      the quality of care, but more evidence is needed before routine use of PROMs can
      be recommended. A structured review was undertaken to examine whether and how
      regular use of PROMs might improve routine practice. METHODS: A systematic search
      of Medline accessed through Webspirs Silverplatter was undertaken for the years
      1976-2004. Controlled trials in English evaluating the impact of clinical use of
      PROMs on routine practice were included. Data regarding study design,
      characteristics of PROMs feedback, patient populations and study results were
      extracted by three reviewers. RESULTS: Feedback of PROMs results to health care
      providers appears to have a substantial impact on some processes of care,
      particularly on diagnosis of mental health conditions. However, the impact on
      patient health status is less consistent. Most of the published studies evaluated
      PROMs as a one-off screening technology and measured only provider behaviours and
      patient health outcomes. CONCLUSIONS: The pattern of results suggests a general
      lack of clarity in the field, especially regarding appropriate goals for PROMs
      and the mechanisms by which they might achieve them. To fully evaluate their role
      in routine practice, studies need to use PROMs that capture issues of importance
      to patients and to measure impacts relating to the patient-provider relationship
      and patient contributions to their well-being. Until studies evaluate PROMs as a
      means facilitate patient-centred care, their full potential in clinical practice
      will remain unknown.

PMID- 16987119
TI  - Patient satisfaction with NHS elective tonsillectomy outsourced to the private
      sector under the Patient Choice Programme.
AB  - RATIONALE, AIMS AND OBJECTIVES: An interim goal of the NHS 'Extending choice for
      patients' initiative was that, by 2004, patients who had been on the NHS waiting
      list for elective surgery for 6 months were provided with a choice of staying on
      the waiting list or being treated faster by opting to have their operation with
      an alternative provider. The aim of this study was to examine patient
      satisfaction in a cohort of patients who travelled out-of-region to undergo
      routine tonsillectomy performed by an NHS consultant at a private hospital.
      METHOD: A questionnaire survey was conducted of adult patients undergoing
      elective tonsillectomy in 2002 and 2003 at The Hampshire Clinic, Basingstoke, UK.
      RESULTS: Our results showed that 95% (n = 123) of patients were happy to travel
      considerable distances from their local hospital to have their operation. Overall
      71% (n = 92) of patients rated the overall experience of having the operation
      performed at the private hospital as excellent and 25% (n = 32) rated it as
      satisfactory. CONCLUSION: We conclude that tonsillectomy performed by a
      consultant in an out-of-region private hospital is associated with a high level
      of patient satisfaction and is an acceptable way to reduce waiting times for
      tonsillectomy provided clear guidelines and safeguards are in place.

PMID- 16987120
TI  - Explaining inequalities in access to treatment in lung cancer.
AB  - BACKGROUND: Geographical inequalities in lung cancer treatment and patient
      survival have been described. We hypothesized that lung cancer patients' access
      to treatment may be influenced by deprivation and the pathway to care. METHODS:
      Case notes were reviewed for patients resident in south-east London who were
      registered with lung cancer at the Thames Cancer Registry in 1998. Use of
      surgery, chemotherapy, radiotherapy or any specific treatment and one-year
      survival were examined. Analyses were adjusted for age, sex, histology, stage and
      basis of diagnosis. RESULTS: Data for 695 out of 958 (73%) patients were
      analysed. Subjects who were initially referred to a specialist in thoracic
      medicine, surgery or oncology were more likely to receive active treatment (71%)
      than subjects who were referred to other consultants (51%) or who were admitted
      as emergencies (42%) (P < 0.0001). CONCLUSION: Socio-economic deprivation was
      associated with lower rates of treatment and this partly explained variations in
      survival. Subjects who were referred to specialists were more likely to receive
      active treatment and treatment patterns varied between first trust attended.

PMID- 16987121
TI  - Sharing specialist skills for diabetes in an inner city: a comparison of two
      primary care organisations over 4 years.
AB  - OBJECTIVE: To evaluate the effects of organizational change and sharing of
      specialist skills and information technology for diabetes in two primary care
      groups (PCGs) over 4 years. METHODS: In PCG-A, an intervention comprised
      dedicated specialist sessions in primary care, clinical guidelines, educational
      meetings for professionals and a shared diabetes electronic patient record (EPR).
      Comparison was made with the neighbouring PCG-B as control. In intervention and
      control PCGs, practice development work was undertaken for a new contract for
      family doctors. Data were collected for clinical measures, practice
      organizational characteristics and professional and patient views. RESULTS: Data
      were analysed for 26 general practices including 17 in PCG-A and nine in PCG-B.
      The median practice-specific proportions of patients with HbA1c recorded annually
      increased in both areas: PCG-A from median 65% to 77%, while PCG-B from 53% to
      84%. For cholesterol recording, PCG-A increased from 50% to 76%, and PCG-B from
      56% to 80%. Organizational changes in both PCGs included the establishment of
      recall systems, dedicated clinics and educational sessions for patients. In both
      PCGs, practices performing poorly at baseline showed the greatest improvements in
      organization and clinical practice. Primary care professionals' satisfaction with
      access and communication with diabetes specialist doctors and nurses increased,
      more so in the intervention PCG. Only 16% of primary care professional
      respondents used the diabetes EPR at least monthly. Patient satisfaction and
      knowledge did not change. CONCLUSIONS: Improvements in practices' organizational
      arrangements were associated with improvements in clinical care in both PCGs.
      Sharing specialist skills in one PCG was associated with increased professional
      satisfaction but no net improvement in clinical measures. A shared diabetes EPR
      is unlikely to be used, unless integrated with practice information systems.

PMID- 16987122
TI  - The Body of Knowledge for the practice of travel medicine--2006.

PMID- 16987123
TI  - Long- and short-haul travel by air: issues for people with diabetes on insulin.
AB  - OBJECTIVE: To determine what problems are experienced by people with diabetes
      mellitus traveling abroad using insulin, whether appropriate and consistent
      advice is available to them, and if necessary, how this advice could be improved
      or enhanced. DESIGN: Census study by self-administered questionnaire of patients
      with diabetes who use insulin attending an outpatient clinic. SETTING: Grampian
      Diabetes Centre, Woolmanhill Hospital, Aberdeen. PARTICIPANTS: A total of 493
      patients using insulin who attended the clinic in Aberdeen over a period of 3
      months. MAIN OUTCOME MEASURES: Determination of number of patients experiencing
      problems during travel, of number of patients seeking advice prior to travel and
      whether it was helpful, and of where respondents would like to access advice.
      RESULTS: About 10% of respondents experienced problems while traveling, mostly
      due to hypoglycemia. Most patients want more advice to be available at the
      clinic. Long-haul travelers were more likely to ask clinic staff for advice and
      were more willing to use a clinic Web site (70%) to access information about
      travel than those traveling shorter distances (54%). CONCLUSIONS: Patient
      education may help to reduce the incidence of problems related to travel in those
      with diabetes mellitus. More than 95% of patients were happy with the advice
      relating to travel health at the clinic but would like more to be available. It
      would be useful to improve the consistency of advice within the clinic, and this
      advice should be readily accessible by all, including fellow healthcare
      professionals such as General Practitioners (GPs), practice nurses, and travel
      clinic staff.

PMID- 16987124
TI  - Awareness of rabies risks and knowledge about preventive measures among
      experienced German travel health advisors.
AB  - BACKGROUND: Every year, millions of people travel to countries where rabies is
      enzootic. However, the quality of rabies-specific information provided by travel
      health advisors and the extent of their knowledge about pre- and postexposure
      prophylaxis have not been examined on a large-scale basis up to now. METHODS:
      5,780 German physicians and pharmacists, who identified themselves as active
      travel health advisors, were chosen from a database. The selected providers were
      asked to complete an Internet-based questionnaire. The form requested both
      demographic information and the assessment of different concrete scenarios, each
      of which featured individuals seeking pre-travel advice on rabies or appropriate
      postexposure treatment after returning from abroad. RESULTS: Overall, 496
      physicians and pharmacists completed the questionnaire. Almost all respondents
      indicated that they would mention the risk of rabies and appropriate preventive
      measures to long-term travelers and tourists planning to visit rural areas.
      However, only 35% to 60% of the advisors would provide this information to
      individuals on business trips, package tours, or travelers in urban centers as
      well. The assessment of the scenarios yielded 51% to 98% of adequate advice.
      Potentially harmful decisions included, for instance, the failure to recommend
      further prophylactic measures after exposure of already vaccinated people or the
      fact that the necessary postexposure prophylaxis was inappropriately withheld in
      cases where treatment had been initially delayed. CONCLUSIONS: Although the
      participants of this study were well aware of the travel-associated rabies risks
      and provided adequate information about this health hazard to most of their
      clients, evident flaws exist regarding the correct assessment of specific
      situations in pre- and postexposure rabies prophylaxis. Our findings therefore
      provide important cues on topics that should be more intensely covered during
      future postgraduate training in travel medicine and also underline the need for
      more practically orientated, readily available information on specific
      prophylactic treatment against rabies.

PMID- 16987125
TI  - Risk of severe acute respiratory syndrome-associated coronavirus transmission
      aboard commercial aircraft.
AB  - BACKGROUND: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV)
      was introduced to the United States through air travel. Although the risk of SARS
      CoV transmission within aircraft cabins has been addressed by several studies,
      the magnitude of the risk remains unclear. METHODS: We attempted to contact all
      persons with working US telephone numbers aboard seven US-bound flights carrying
      SARS patients. Consenting participants responded to a questionnaire, and a serum
      sample was collected at least 38 days after the flight and tested for SARS-CoV
      associated antibodies. Participants reporting an illness compatible with SARS,
      with onset during the 2- to 10-day incubation period, were considered suspect
      cases; positive serology was required for confirmed cases. RESULTS: Among 1,766
      passengers and crew, 339 (19%) persons were contacted. Of these, 312 (92%)
      completed questionnaires, and blood was collected from 127 (37%). Serology was
      negative for all 127 participants, including three of four who met the clinical
      case criteria for SARS, and the fourth had a mild illness that lasted only 5
      days. CONCLUSIONS: Transmission of SARS-associated CoV was not observed,
      suggesting that the risk of transmission is not amplified aboard aircraft.

PMID- 16987126
TI  - Hepatitis B risks and immunization coverage among American travelers.
AB  - BACKGROUND: Hepatitis B is endemic in much of Asia, Africa, and parts of South
      America, regions that are increasingly popular destinations for American
      travelers. The frequency of hepatitis B risks during travel has been examined for
      Europeans but not Americans. Further, limited data are available to describe the
      domestic hepatitis B risk factors of American travelers, the proportion
      vaccinated, and whether immunization activities target travelers at highest risk.
      We conducted a survey of international travelers to address these issues.
      METHODS: A survey was mailed to 884 American international travelers, of whom 618
      (70%) responded. The survey covered demographic and travel characteristics,
      sources of pre-travel health advice, immunization status, and items needed to
      assess hepatitis B vaccination candidacy. Travel-specific items concerned the
      most recent trip to a hepatitis B endemic region. Hepatitis B risk during the
      most recent trip was classified as high, potential, or none based on potential
      exposure to blood or bodily fluids. RESULTS: Only 31% of respondents visited any
      health practitioner to obtain pre-travel health advice; 13% visited a travel
      medicine specialist. Totally 45% of respondents reported (3)1 domestic or travel
      related hepatitis B risk, and 8% were at high risk during travel. Risk factors
      were more common among younger travelers and those with longer travel durations.
      Travel medicine specialists were more likely than nonspecialists to provide
      hepatitis B vaccine (40% vs 21%, p= 0.01). Travelers with risk factors were no
      more likely to be vaccinated in specialist or nonspecialist settings. Upon
      departure, only 19% of all travelers and 30% of travelers with risk factors had
      received three or more hepatitis B vaccine doses. CONCLUSIONS: Most US travelers
      to hepatitis B endemic regions do not secure pre-travel health advice, and most
      have not received three doses of hepatitis B vaccine. A substantial share are
      candidates for hepatitis B vaccination based on their domestic activities, and/or
      face hepatitis B risks during travel.

PMID- 16987127
TI  - Pharmacists and travel advice for tropics in Lisbon (Portugal).
AB  - BACKGROUND: In Portugal, little is known about the quality of advice given to
      international travelers by pharmacists. The aim of this study was to determine
      pharmacists' training, experience, and interest in travel medicine and to assess
      the technical quality of the information given. METHODS: We sent a postal
      questionnaire to all pharmacies in the Lisbon area. The technical director or
      another graduate pharmacist was asked to complete the questionnaire. RESULTS: A
      total of 251 pharmacists participated in the study. Most of them (93.2%) did not
      have any training in travel medicine, and most of them expressed a wish to be
      informed and/or updated on this subject. The number of advised travelers was low.
      The use of repellent, protective clothes, and mosquito bed nets was the most
      frequent advice on protection against mosquito bites. From a subgroup of 170
      pharmacists, 43.5% indicated mefloquine and 44.1% indicated chloroquine as
      malaria chemoprophylaxis to African countries. A significant association existed
      between the variables "to indicate mefloquine" and "seeks to be informed/updated
      on travel medicine." Those who indicated chloroquine tended to like travel
      medicine less. Concerning diarrhea prevention and treatment, the consumption of
      bottled and/or treated water and the administration of antibiotics during the
      episode were the most reported advice. Concerning vaccination against yellow
      fever, only 8 of 91 pharmacists correctly indicated all Portuguese-speaking
      countries with and without the risk of this disease. CONCLUSIONS: Studied
      pharmacists need training in travel medicine. Travel advice was incomplete and/or
      incorrect and must be improved.

PMID- 16987128
TI  - Quality assessment in a travel clinic: a study of travelers' knowledge about
      malaria.
AB  - BACKGROUND: Quality in health care delivery is considered essential and should be
      expected for all who deliver health care. We were not able to identify in
      Portugal any previous studies that assessed the quality of travel medicine
      consultations. The aims of this study was to assess the impact of travel health
      advice on travelers' knowledge and the quality of the outcome of the travel
      consultations at the Institute of Hygiene and Tropical Medicine, Portugal.
      METHOD: We selected the quasi-experimental model "separate-sample pretest
      posttest design." Two random samples were obtained (control and experimental
      groups). An anonymous self-administered questionnaire was applied during the
      second half of 2002, until we had received about 200 questionnaires for each
      group. The questions assessed travelers' knowledge of malaria, its transmission,
      prevention, and clinical features. RESULTS: There was a significant improvement
      of travelers' knowledge in the postconsultation group, with 98.5% of individuals
      understanding that malaria is transmitted by mosquito bite (p= 0.005), 91.5% that
      malaria may be prevented by appropriate prophylactic medication (p= 0.007), and
      93% knowing that malaria is prevented by avoiding mosquito bites (p= 0.003).
      However, almost half of the postconsultation group did not realize that there was
      no vaccine available for preventing malaria (p < 0.001) or that avoiding unsafe
      food and drink did not prevent malaria (p= 0.006). About 53% gave correct answers
      about malaria incubation periods (p < 0.001), and 91.1% were able to identify the
      initial symptoms of malaria (p < 0.001). CONCLUSIONS: Travel medicine
      consultations increase the knowledge base of travelers but do not achieve 100%
      correct answers. Our results suggest that during a travel health consultation,
      critical information is assimilated about the prevention of malaria, but myths
      and misunderstandings that are held by travelers are not completely dispelled.

PMID- 16987129
TI  - Health information given by Swiss travel agencies.
AB  - BACKGROUND: Many of the 1 million Swiss traveling to tropical or subtropical
      countries book their trip through travel agencies every year. These agencies are
      thus an important source of information about malaria and other important health
      risks and little is known about the appropriate health information provided by
      these. METHOD: A study was conducted to assess health-related information in
      members of the Swiss Federation of Travel Agencies in the metropolitan area of
      Zurich, Switzerland. A covert investigator (F.M.S.) visited these agencies and
      requested information on a package holiday for 2 or 3 weeks to Kenya. Following
      an in-person interview, the investigator recorded any health-related information
      provided on a pretested form. If none was mentioned, the agent was prompted using
      a standardized procedure. RESULTS: A total of 88 agencies were visited.
      Spontaneous health advice was given in 44% of all visits. After prompting, 99% of
      all travel agents mentioned preventive measures against malaria, but only 69%
      indicated the need for vaccinations against other diseases. Spontaneous advice on
      malaria risk and vaccinations was better than advice given upon prompting. One
      fifth of all travel agents neither mentioned malaria prevention measures
      spontaneously nor recommended seeing a health specialist. CONCLUSIONS: Overall,
      travel medicine knowledge of travel agents in the Zurich area needs improvement
      as many tended to draw attention to health risks only when prompted. Attitude,
      personal knowledge, and experience of individual travel agents were key to the
      health information given. Up-to-date and readily available information on health
      risks should be provided to travel agencies and structured training given in
      collaboration with health professionals.

PMID- 16987130
TI  - Travel and sexually transmitted infections.
AB  - Increasing population mobility and increasing frequency and variety of sexually
      transmitted infections (STI) are closely linked around the globe. Although all
      mobile populations are at increased risk for acquiring STIs, international
      travelers are the focus of this review. Several aspects of travel such as
      opportunity, isolation, and the desire for unique experiences all enhance the
      likelihood of casual sexual experiences while abroad. The situational loss of
      inhibition of travel can be markedly enhanced by alcohol and drugs. Several of
      the most important elements of the complex interaction between travel and STIs
      are discussed.

PMID- 16987131
TI  - Melioidosis: an imported case from Madagascar.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in
      Southeast Asia and Northern Australia but is a rare pathogen in other parts of
      the world. No human case of melioidosis has been reported in Madagascar until
      now. We describe a case of pulmonary melioidosis probably acquired in Madagascar.

PMID- 16987132
TI  - Prototheca wickerhamii hand infection successfully treated by itraconazole and
      voriconazole.

PMID- 16987134
TI  - Quinine sulfate inhibits invasion of Salmonella typhimurium and Shigella
      flexneri: a preliminary study.

PMID- 16987135
TI  - Acute respiratory distress syndrome in Plasmodium vivax malaria in traveler
      returning from Venezuela.

PMID- 16987137
TI  - Enteric fever in Israel travelers: a nationwide study.

PMID- 16987139
TI  - Cytomics emerging from cytometry.

PMID- 16987140
TI  - Intestinal crypt properties fit a model that incorporates replicative ageing and
      deep and proximate stem cells.
AB  - A model of intestinal crypt organization is suggested based on the assumption
      that stem cells have a finite replicative life span. The model assumes the
      existence in a crypt of a quiescent ('deep') stem cell and a few more actively
      cycling ('proximate') stem cells. Monte Carlo computer simulation of published
      intestinal crypt mutagenesis data is used to test the model. The results of the
      simulation indicate that stabilization of the crypt mutant phenotype following
      treatment with external mutagen is consistent with a stem cell replicative life
      span of about 40 divisions for mouse colon and 90-100 divisions for mouse small
      intestine, corresponding to a deep stem cell cycle time of about 3.9 and 8.5
      weeks for colon and small intestine, respectively. Simulation of the data
      obtained for human colorectal crypts suggests that the proximate stem cell cycle
      time is about 80 h, assuming a replicative life span of 50-150 divisions, and
      that the deep stem cell divides approximately every 30 weeks.

PMID- 16987141
TI  - An enteroendocrine cell-based model for a quiescent intestinal stem cell niche.
AB  - We have shown that the kinetics of conversion of intestinal crypt cell
      populations to a partially or wholly mutant phenotype are consistent with a model
      in which each crypt contains an infrequently dividing 'deep' stem cell that is
      the progenitor of several more frequently dividing 'proximate' stem cells. An
      assumption of our model is that each deep stem cell exists in a growth inhibitory
      niche. We have used information from the literature to develop a model for a
      quiescent intestinal stem cell niche. This niche is postulated to be primarily
      defined by an enteroendocrine cell type that maintains stem cell quiescence by
      secretion of growth inhibitory peptides such as somatostatin and
      guanylin/uroguanylin. Consistent with this model, there is evidence that the
      proteins postulated as defining a growth-inhibitory stem cell niche can act as
      intestinal tumour suppressors. Confirmation that a growth-inhibitory niche does
      exist would have important implications for our understanding of intestinal
      homeostasis and tumorigenesis.

PMID- 16987142
TI  - A simple device to rapidly prepare whole mounts of murine intestine.
AB  - Many mouse models of neoplasia and pre-neoplasia require the examination of whole
      mounts of the gastrointestinal tract. A simple device has been produced to
      facilitate the rapid preparation of mouse intestines for subsequent
      quantification of tumours and pre-neoplastic lesions such as aberrant crypt foci.
      The device greatly speeds up the production of whole mounts and also provides far
      more consistent and better-quality preparations.

PMID- 16987143
TI  - The reversion to diploid cells from established triploid V79 cells.
AB  - The triploid V79 cells are stable under usual culture conditions, and do not
      revert to being diploid. Here, the triploid-diploid transition of triploid V79
      cells has been successfully induced in suspension culture in culture dishes with
      untreated surfaces. The diploid cells began to appear in a population of triploid
      V79 cells cultured under these conditions for 4 weeks. All of the triploid cells
      were transformed to diploid through subsequent monolayer culture for 5 weeks. It
      was confirmed that the revertant diploid cells had the same characteristics as
      original diploid V79 cells, with respect to DNA histograms, cell volume and
      chromosome number. Thus, it seems that suspension culturing is an important
      factor that induces the triploid-diploid transition.

PMID- 16987144
TI  - Effect of over-expression of neuropathy target esterase on mammalian cell
      proliferation.
AB  - Neuropathy target esterase (NTE), the human homologue of a protein required for
      brain development in Drosophila, is expressed primarily in neural cells but is
      also detected in non-neural cells. Although NTE has been proposed to play a role
      in neurite outgrowth and process elongation during neurodifferentiation, the
      function of NTE has not been defined in neural cells. In this study we have
      investigated the possible role of NTE in neuroblastoma cells and non-neural cells
      using an over-expression strategy. Over-expression of NTE in human neuroblastoma
      SH-SY5Y cells and monkey kidney COS7 cells led to an accumulation of NTE on the
      cytoplasmic surface of the endoplasmic reticulum and inhibition of cell
      proliferation. In particular, high levels of NTE arrested COS7 cells at G2/M
      stage yet was not associated with arrest at a particular phase of the cell cycle
      in SH-SY5Y cells. Moreover, over-expression of NTE did not induce apoptosis in
      two kinds of cell lines as assessed by flow cytometry. These results suggest that
      the role of NTE over-expression in cell proliferation is associated with
      different mechanisms in different cells.

PMID- 16987145
TI  - A response to The effects of vascular disease on late onset Parkinson's disease
      (Papapetropoulos et al.).

PMID- 16987151
TI  - Different types of intra-saccadic slowing in congenital (RAPSN-mutation) and
      acquired myasthenic syndromes.

PMID- 16987152
TI  - Acute encephalopathy after intravenous administration of valproate in non
      convulsive status epilepticus.

PMID- 16987153
TI  - Moyamoya syndrome in a Caucasian woman with Turner's syndrome.

PMID- 16987155
TI  - Prevention of nervous system damage in thiamine deficiency.

PMID- 16987156
TI  - EFNS guidelines on management of narcolepsy.
AB  - Management of narcolepsy with or without cataplexy relies on several classes of
      drugs, namely stimulants for excessive daytime sleepiness and irresistible
      episodes of sleep, antidepressants for cataplexy and hypnosedative drugs for
      disturbed nocturnal sleep. In addition, behavioral measures can be of notable
      value. Guidelines on the management of narcolepsy have already been published.
      However contemporary guidelines are necessary given the growing use of modafinil
      to treat excessive daytime sleepiness in Europe within the last 5-10 years, and
      the decreasing need for amphetamines and amphetamine-like stimulants; the
      extensive use of new antidepressants in the treatment of cataplexy, apart from
      consistent randomized placebo-controlled clinical trials; and the present re
      emergence of gamma-hydroxybutyrate under the name sodium oxybate, as a treatment
      of all major symptoms of narcolepsy. A task force composed of the leading
      specialists of narcolepsy in Europe has been appointed. This task force conducted
      an extensive review of pharmacological and behavioral trials available in the
      literature. All trials were analyzed according to their class evidence.
      Recommendations concerning the treatment of each single symptom of narcolepsy as
      well as general recommendations were made. Modafinil is the first-line
      pharmacological treatment of excessive daytime sleepiness and irresistible
      episodes of sleep in association with behavioral measures. However, based on
      several large randomized controlled trials showing the activity of sodium
      oxybate, not only on cataplexy but also on excessive daytime sleepiness and
      irresistible episodes of sleep, there is a growing practice in the USA to use it
      for the later indications. Given the availability of modafinil and
      methylphenidate, and the forseen registration of sodium oxybate for narcolepsy
      (including excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep) in
      Europe, the place of other compounds will become fairly limited. Since its recent
      registration cataplexy sodium oxybate has now become the first-line treatment of
      cataplexy. Second-line treatments are antidepressants, either tricyclics or newer
      antidepressants, the later being increasingly used these past years despite few
      or no randomized placebo-controlled clinical trials. As for disturbed nocturnal
      sleep the best option is still hypnotics until sodium oxybate is registered for
      narcolepsy. The treatments used for narcolepsy, either pharmacological or
      behavioral, are diverse. However the quality of the published clinical evidences
      supporting them varies widely and studies comparing the efficacy of different
      substances are lacking. Several treatments are used on an empirical basis,
      specially antidepressants for cataplexy, due to the fact that these medications
      are already used widely in depressed patients, leaving little motivation from the
      manufacturers to investigate efficacy in relatively rare indications. Others, in
      particular the more recently developed substances, such as modafinil or sodium
      oxybate, are evaluated in large randomized placebo-controlled trials. Our
      objective was to reinforce the use of those drugs evaluated in randomized placebo
      controlled trials and to reach a consensus, as much as possible, on the use of
      other available medications.

PMID- 16987157
TI  - EFNS guidelines on management of restless legs syndrome and periodic limb
      movement disorder in sleep.
AB  - In 2003, the EFNS Task Force was set up for putting forth guidelines for the
      management of the Restless Legs Syndrome (RLS) and the Periodic Limb Movement
      Disorder (PLMD). After determining the objectives for management and the search
      strategy for primary and secondary RLS and for PLMD, a review of the scientific
      literature up to 2004 was performed for the drug classes and interventions
      employed in treatment (drugs acting on the adrenoreceptor, antiepileptic drugs,
      benzodiazepines/hypnotics, dopaminergic agents, opioids, other treatments).
      Previous guidelines were consulted. All trials were analysed according to class
      of evidence, and recommendations formed according to the 2004 EFNS criteria for
      rating. Dopaminergic agents came out as having the best evidence for efficacy in
      primary RLS. Reported adverse events were usually mild and reversible;
      augmentation was a feature with dopaminergic agents. No controlled trials were
      available for RLS in children and for RLS during pregnancy. The following level A
      recommendations can be offered: for primary RLS, cabergoline, gabapentin,
      pergolide, ropinirole, levodopa and rotigotine by transdermal delivery (the
      latter two for short-term use) are effective in relieving the symptoms.
      Transdermal oestradiol is ineffective for PLMD.

PMID- 16987159
TI  - Thiamine (vitamin B1) deficiency and associated brain damage is still common
      throughout the world and prevention is simple and safe!
AB  - Many different population groups throughout the world have thiamine deficiency
      and are at risk of developing severe neurological and cardiac disorders.
      Alcoholics are most at risk but other important clinical groups should be
      monitored carefully. The most severe, potentially fatal disease caused by
      thiamine deficiency is the neurological disorder Wernicke-Korsakoff syndrome.
      This can be difficult to diagnose and many cases remain undiagnosed. Treatment
      with thiamine generally results in a dramatic clinical improvement. Thiamine
      supplementation of stable food products like flour is an effective, simple and
      safe public health measure that can improve the thiamine status of all population
      groups.

PMID- 16987158
TI  - EFNS guidelines on the treatment of cluster headache and other trigeminal
      autonomic cephalalgias.
AB  - Cluster headache and the other trigeminal-autonomic cephalalgias [paroxysmal
      hemicrania, short-lasting unilateral neuralgiform headache attacks with
      conjunctival injection and tearing (SUNCT) syndrome] are rare but very disabling
      conditions with a major impact on the patient's quality of life. The objective of
      this study was to give evidence-based recommendations for the treatment of these
      headache disorders based on a literature search and consensus amongst a panel of
      experts. All available medical reference systems were screened for any kind of
      studies on cluster headache, paroxysmal hemicrania and SUNCT syndrome. The
      findings in these studies were evaluated according to the recommendations of the
      European Federation of Neurological Societies resulting in level A, B or C
      recommendations and good practice points. For the acute treatment of cluster
      headache attacks, oxygen (100%) with a flow of at least 7 l/min over 15 min and 6
      mg subcutaneous sumatriptan are drugs of first choice. Prophylaxis of cluster
      headache should be performed with verapamil at a daily dose of at least 240 mg
      (maximum dose depends on efficacy or tolerability). Although no class I or II
      trials are available, steroids are clearly effective in cluster headache.
      Therefore, the use of at least 100 mg methylprednisone (or equivalent
      corticosteroid) given orally or at up to 500 mg i.v. per day over 5 days (then
      tapering down) is recommended. Methysergide, lithium and topiramate are
      recommended as alternative treatments. Surgical procedures, although in part
      promising, require further scientific evaluation. For paroxysmal hemicranias,
      indomethacin at a daily dose of up to 225 mg is the drug of choice. For treatment
      of SUNCT syndrome, large series suggest that lamotrigine is the most effective
      preventive agent, with topiramate and gabapentin also being useful. Intravenous
      lidocaine may also be helpful as an acute therapy when patients are extremely
      distressed and disabled by frequent attacks.

PMID- 16987160
TI  - Onset and progression of primary torsion dystonia in sporadic and familial cases.
AB  - Four hundred and sixty records of patients with primary torsion dystonia (296
      women and 164 men) were evaluated. The mean age at disease onset was 48.3 +/-
      17.7 years; 13 patients carried the DYT1 CAG deletion. The distribution of age at
      onset was represented by a bi-modal curve, with a nadir at 21 year separating
      early onset from late onset cases. In 15.9% of cases there was a positive family
      history of dystonia. Cranial, cervical or lower limb onset was more common
      amongst women (M:F ratios were 1:2.7, 1:1.9, and 1:3); by contrast, onset in the
      upper limb was more common in men (M:F ratio 2.2:1). As expected, disease
      progression was more pronounced in cases with early onset; it was reckoned that
      onset at or above 32 years was associated with a negligible likelihood to
      progress to a generalized form. The mean age at onset of familial cases was 44.8
      +/- 11.2 years, significantly lower than the mean age at onset of sporadic cases
      (53.5 +/- 13.4 years). Familial cases were characterized by more sites involved
      throughout disease course. Familial cases had a higher tendency to progress to a
      segmental or generalized form than sporadic cases.

PMID- 16987161
TI  - Neurological complications of prolonged hunger strike.
AB  - We investigated neurological findings in 41 prisoners (mean age: 28.6) who
      participated in a hunger strike between 2000 and 2002. All cases were evaluated
      using neuropsychological, neuroradiological, and electrophysiological methods.
      The total duration of fasting ranged from 130 to 324 days (mean 199 days). All
      cases had 200-600 mg/day thiamine orally for 60-294 days (mean 156) during the
      hunger strike, and had neurological findings consistent with Wernicke-Korsakoff
      syndrome. All 41 patients exhibited altered consciousness which lasted from 3 to
      31 days. All patients also presented gaze-evoked horizontal nystagmus and truncal
      ataxia. Paralysis of lateral rectus muscles was found in 14. Amnesia was apparent
      in all cases. Abnormal nerve conduction study parameters were not found in the
      patient group, but the amplitude of compound muscle action potential of the
      median and fibular nerves and sensory nerve action potential amplitude of the
      sural nerve were lower than the control group, and distal motor latency of the
      posterior tibial nerve was significantly prolonged as compared with the control
      group. The latency of visual evoked potential was prolonged in 22 cases.
      Somatosensory evoked potential (P37) was prolonged but not statistically
      significant. Our most significant finding was that the effect of hunger was more
      prominent on the central nervous system than on the neuromuscular system, despite
      the fact that all patients were taking thiamine. In our opinion, partial recovery
      of neurological, and neurocognitive signs in prolonged hunger could be a result
      of permanent neurological injury.

PMID- 16987162
TI  - Matrix metalloproteinases 2 and 9 in human atherosclerotic and non
      atherosclerotic cerebral aneurysms.
AB  - Matrix metalloproteinases 2 and 9 (MMP 2 and -9) have been implicated in the
      pathogenesis of atherosclerosis and aneurysm formation. The goal of the study was
      to establish the role of these metalloproteinases in both human atherosclerotic
      and non-atherosclerotic cerebral aneurysms. Eleven cerebral aneurysms (four
      atherosclerotic, seven non-atherosclerotic) were immunohistochemically stained
      for MMP 2 and -9. As controls, atherosclerotic and normal Circle of Willis
      arteries were similarly immunostained. All specimens were retrieved at autopsy
      and were paraffin-embedded. In order to evaluate the real MMP 2 and -9
      activities, gelatin zymography was also performed in only two available specimens
      of non-atherosclerotic intracranial aneurysms, because of the relative
      unavailability of fresh intracranial aneurysm tissue (i.e. reluctance to excise
      the aneurysm fundus at surgery). Our data establish that MMP 2 and -9 were
      expressed minimally or not at all in normal Circle of Willis arteries but were
      strongly expressed in medial smooth muscle cells of atherosclerotic Circle of
      Willis arteries. In the aneurysm group, both MMP 2 and -9 were strongly expressed
      in the atherosclerotic aneurysms, but MMP 2 alone was detected in the non
      atherosclerotic aneurysms. Zymography revealed a weak enzyme activity correlating
      to MMP 9 standard recombinant protein. MMP 2 activity was not demonstrated in
      either specimen. This study shows that the expression of MMP 2 and -9 is
      associated with atherosclerosis, be it in aneurysmal or non-aneurysmal cerebral
      vessels but MMP 2 appears to be specifically expressed in aneurysms devoid of
      atherosclerosis perhaps suggesting a pathogenic role for MMP 2 in the alteration
      of the extracellular matrix of cerebral arteries during aneurysm formation.

PMID- 16987163
TI  - A pilot study on systemic thrombolysis followed by low molecular weight heparin
      in ischemic stroke.
AB  - Low molecular weight heparin (LMWH) administered immediately after intravenous
      thrombolysis (IT) may reduce the risk of arterial re-occlusion. Its benefit,
      however, may not outweigh the risk of intracranial hemorrhage (ICH). We sought
      preliminary data regarding safety of this combined therapy in an open-label, non
      randomized study. The patients received either a standard anticoagulation (AC)
      starting 24 h after IT (the standard AC group) or AC with 2850 IU of nadroparin,
      given every 12 h immediately after IT (the early AC group). Sixty patients
      received IT treatment: 25 in the standard AC group [mean age 66, median National
      Institutes of Health Stroke Scale (NIHSS) 13, 64% men] and 35 in the early AC
      group (mean age 68, median NIHSS 13, 69% men). Symptomatic ICH occurred in one
      patient (4%) in the standard AC group and three patients (8.6%) in the early AC
      group [odds ratio (OR) 1.8; 95%CI 0.2-12.8]. At 3 months, nine patients in the
      standard AC group (36%) and 16 patients in the early AC group (45.7%) achieved a
      modified Rankin scale 0 or 1 (OR 1.2; 95%CI 0.5-3.2). Our study suggests that
      treatment with LMWH could be associated with higher odds of ICH, although it may
      not necessarily lead to a worse outcome. This justifies larger clinical trials.

PMID- 16987164
TI  - Bowel dysfunction in patients with cauda equina lesions.
AB  - Despite their serious sequels on bowel function, lesions of the cauda equina have
      not been previously systematically studied in larger patient populations. This
      was the aim of the present report. From the registrars of a diagnostic and
      rehabilitation centres 67 patients with clinical, electrodiagnostic and
      radiological findings supportive of the cauda equina lesions were recruited. The
      Slovene versions of the standard questionnaires for anal incontinence and
      constipation were used. The responses were scored, impairments categorized and
      previous treatments noted. Neurological examination, electromyography (EMG) of
      lumbo-sacral myotomes, quantitative anal sphincter EMG and electromyographic
      evaluation of the sacral reflex were performed. Severe anal
      incontinence/constipation was reported by 18%/0%, moderate by 36%/33%, and slight
      by 28%/43% of our patients. Twenty-one per cent of patients wore pads
      continuously and 14% occasionally. More than half of the patients (60%) reported
      changes in their lifestyle due to anal incontinence. No patient had completely
      normal findings on neurological examination. Perianal sensory loss correlated (P
      < 0.05) with anal incontinence and gender with constipation (women > men). Only
      two patients had received medical attention for bowel dysfunction. Study thus
      demonstrated significant bowel impairment in patients with lesions of the cauda
      equina, which has received insufficient medical attention.

PMID- 16987165
TI  - Release of glial fibrillary acidic protein is related to the neurovascular status
      in acute ischemic stroke.
AB  - This study aimed at an analysis of glial fibrillary acidic protein (GFAP) in
      acute ischemic stroke, its association with the neurovascular status and its
      potential value as monitoring parameter. In 53 consecutive patients, serial
      venous blood samples were taken on admission, 6, 12, 18, 24, 48, 72, 96, and 120
      h after stroke onset. The neurovascular status was assessed by repetitive
      extracranial and transcranial duplex sonography. Neurologic deficits were
      quantified by the National Institutes of Health stroke scale, and functional
      outcome was assessed with the modified Rankin Scale. Mean GFAP values were
      elevated from admission on with highest levels 48 h after stroke onset. GFAP
      release was highly correlated with severity of neurologic deficits and infarct
      volume. In patients with persistent middle cerebral artery occlusion, GFAP
      increased significantly compared with patients with normal sonographic findings
      (P = 0.019) and recanalization after thrombolysis resulted in a significant
      reduced increase (P = 0.038). GFAP concentrations were associated with the
      functional outcome after 3 months. Release kinetics of GFAP are associated with
      patients clinical deficits and infarct volume, depend on the neurovascular status
      on admission and on early recanalization after thrombolysis, and may be used as
      an additional predictor of the early course and functional outcome.

PMID- 16987166
TI  - Different patterns of Mini Mental Status Examination responses in primary
      progressive aphasia and Alzheimer's disease.
AB  - Primary progressive aphasia (PPA) syndrome is frequently misdiagnosed-
      particularly in favour of Alzheimer's disease (AD). Misdiagnosis is related to
      the heterogeneity of language disorders at onset, variability in the rate of
      clinical progression and the low prevalence of PPA syndrome, compared with AD.
      The aim of this study was to determine whether a patient's first Mini Mental
      Status Examination (MMSE) might provide insight into differentiating between PPA
      and AD. We compared item scores for the first, complete MMSE in consecutive
      patients with PPA versus matched patients with AD. Word recall and constructional
      praxis were significantly better in patients subsequently diagnosed as suffering
      from PPA. Patients with AD performed significantly better in terms of word
      registration, object naming, repetition and verbal direction. Our findings
      indicate that the various MMSE item scores may be helpful in differentiating PPA
      and AD in the first few years of the disease.

PMID- 16987167
TI  - Spontaneous cerebrospinal fluid hypovolaemia: a therapeutic dilemma?
AB  - Spontaneous intracranial hypotension is characterized by orthostatic headaches in
      conjunction with reduced cerebrospinal fluid volume (CSF) and characteristic
      imaging findings. We report the clinical course of six consecutive patients with
      spontaneous intracranial hypotension who were followed between 4 months and 2.5
      years. The characteristic orthostatic headaches were present in five patients.
      Diffuse pachymeningeal enhancement on brain magnetic resonance imaging (MRI) was
      evident in all cases. CSF detected elevated protein content in three of six
      patients. In only two of our six patients a first epidural blood patch resulted
      in complete symptom resolution lasting 4 months and 1 year. Four patients
      received a second epidural blood patch and one patient also received a third. In
      four patients, follow-up brain MRI revealed re-occurrence of the typical MRI
      features and all of them suffered from orthostatic symptoms at this time. Only
      four patients are free of complaints after an average follow-up period of 10
      months. Symptom relief within 7 days from an epidural blood patch is accepted to
      be diagnostic for spontaneous intracranial hypotension. However, our data
      illustrate that the clinical course of the syndrome is very unstable and the
      epidural blood patch is less effective than widely accepted.

PMID- 16987168
TI  - Neuropsychological profiles of manganese neurotoxicity.
AB  - The etiology of manganese neurotoxicity is heterogenous and includes exposure to
      welding fumes, chronic liver failure, and chronic total parental nutrition (TPN).
      We recently reported that cognitive impairment occurs in welders and patients
      with chronic liver failure who had evidence of manganese neurotoxicity including
      abnormal magnetic resonance imaging (MRI) basal ganglia T1 hyperintensity. In
      this study, we compared the neuropsychological profiles of patients with
      manganese neurotoxicity and basal ganglia T1 hyperintensities from three
      different etiologies: welding, chronic liver failure, and chronic TPN. Across all
      three groups, the neuropsychological profiles suggest frontal and subcortical
      cognitive impairment, with more widespread abnormalities occurring in the non
      welding groups.

PMID- 16987169
TI  - Oxcarbazepine and atypical evolution of benign idiopathic focal epilepsy of
      childhood.
AB  - Patients that have benign epilepsy with centrotemporal spikes (BECTS) may
      occasionally experience an atypical development in their course when treated with
      drugs such as carbamazepine. Three patients with electroclinical patterns
      consistent with BECTS showed seizure exacerbation during oxacarbazepine (OXC)
      therapy. Two manifested atypical absences, neuropsychological disturbances, and
      generalized spike-and-wave discharges in their electroencephalograms (EEGs) that
      became continuous during sleep. The third patient showed, during OXC therapy,
      more frequent partial motor seizures which ended with ictal vomiting and post
      ictal obnubilation. EEGs recorded during sleep showed discontinuous paroxysmal
      activity in the right centrotemporal area. Symptoms were reversed following
      discontinuation of the OXC therapy. Although electroclinical findings were
      consistent with a BECTS diagnosis, all patients had some atypical features. Our
      observations show that BECTS patients, in particular those presenting with
      atypical findings, might be at risk for developing paradoxical reactions to OXC
      therapy. We suggest that OXC should be included in the list of drugs that may
      cause electroclinical deterioration in these patients.

PMID- 16987170
TI  - Placebo-controlled trial of riluzole in multiple system atrophy.
AB  - We performed a placebo-controlled cross-over trial of riluzole (100 mg b.i.d.) in
      10 patients with probable multiple system atrophy (MSA) administering riluzole
      and placebo for 4 weeks each with a 4-week washout period. Outcome measures
      evaluated short-term anti-Parkinsonian effects using the Unified Parkinson's
      Disease Rating Scale (UPDRS) subscales (UPDRS-II, activities of daily living;
      UPDRS-III, motor examination; sum of UPDRS-II and -III) before and at the end of
      each treatment phase. Delta values were calculated by subtracting the UPDRS
      scores measured at the end of each treatment arm from those before onset of each
      medication phase. Riluzole was generally well tolerated. There were no
      significant anti-Parkinsonian effects of riluzole comparing the UPDRS delta
      values for both treatment arms using the Wilcoxon signed-rank test. It is
      unlikely that riluzole treatment could have clinically meaningful anti
      Parkinsonian effects in MSA. A trial assessing the disease-modifying potential of
      riluzole in MSA is underway.

PMID- 16987171
TI  - Novel C59T leader peptide mutation in the MPZ gene associated with late-onset,
      axonal, sensorimotor polyneuropathy.
AB  - The objective of this study was to report a novel exon-1 mutation in the myelin
      protein zero (MPZ) gene, resulting in axonal Charcot-Marie-Tooth neuropathy with
      recurrent hyper-CK-emia. In a 64-year-old woman slowly progressive distal lower
      limb weakness, muscle cramps in the lower limb muscles, and stocking-type
      numbness had developed from the age of 61. Neurologic examination revealed
      discrete hip flexor weakness, weakness for foot extension, diffuse wasting of the
      distal lower limb muscles, reduced patella tendon reflexes, and absent Achilles
      tendon reflexes. There was recurrently elevated creatine kinase with a maximum of
      607 U/l (n, <145 U/l). Stimulation of the peroneal and tibial nerves did not
      evoke a muscular response. Electromyography was neurogenic. Biopsy of the right
      sural nerve showed diffuse axonal degeneration and loss of axons of all
      diameters. Muscle biopsy showed increased fiber-size variability, angulated
      fibers, internalized nuclei, accumulations of nuclei, grouped atrophic muscle
      fibers, and fiber splitting. Molecular genetic analysis by PCR and direct
      nucleotide sequencing revealed the heterozygous C59T exon-1 MPZ gene mutation,
      resulting in the amino acid exchange S20F of the MPZ signal protein domain
      (leader peptide). The novel C59T mutation in the leader peptide of the MPZ gene
      is pathogenic and manifests as severe, late-onset, axonal, symmetric sensorimotor
      polyneuropathy (CMT2) and hyper-CK-emia.

PMID- 16987172
TI  - Understanding the shapes of bacteria just got more complicated.
AB  - The paper by Briegel et al. in this issue of Molecular Microbiology uses advanced
      cryo-transmission electron microscopy (cryoTEM) techniques to reveal four
      separate locations of cytoplasmic filament bundles in Caulobacter crescentus.
      Intuitively, these filaments should be rather rigid protein structures and
      composed of previously identified shape-forming proteins, such as crescentin or
      MreB. Yet, deletion mutants lacking these proteins still possessed filaments and
      still possessed wild-type morphology. These results suggest that a complex
      combination of protein structures, including those of crescentin, MreB and these
      newly identified bundles, in combination with the cell envelope help maintain the
      complicated shape of C. crescentus. Other bacteria might have similar
      architectural proteins to assist in maintaining the cell contours during growth
      and division.

PMID- 16987173
TI  - Multiple large filament bundles observed in Caulobacter crescentus by electron
      cryotomography.
AB  - While the absence of any cytoskeleton was once recognized as a distinguishing
      feature of prokaryotes, it is now clear that a number of different bacterial
      proteins do form filaments in vivo. Despite the critical roles these proteins
      play in cell shape, genome segregation and cell division, molecular mechanisms
      have remained obscure in part for lack of electron microscopy-resolution images
      where these filaments can be seen acting within their cellular context. Here,
      electron cryotomography was used to image the widely studied model prokaryote
      Caulobacter crescentus in an intact, near-native state, producing three
      dimensional reconstructions of these cells with unprecedented clarity and
      fidelity. We observed many instances of large filament bundles in various
      locations throughout the cell and at different stages of the cell cycle. The
      bundles appear to fall into four major classes based on shape and location,
      referred to here as 'inner curvature', 'cytoplasmic', 'polar' and 'ring-like'. In
      an attempt to identify at least some of the filaments, we imaged cells where
      crescentin and MreB filaments would not be present. The inner curvature and
      cytoplasmic bundles persisted, which together with their localization patterns,
      suggest that they are composed of as-yet unidentified cytoskeletal proteins. Thus
      bacterial filaments are frequently found as bundles, and their variety and
      abundance is greater than previously suspected.

PMID- 16987174
TI  - The role of nutrient regulation and the Gpa2 protein in the mating pheromone
      response of C. albicans.
AB  - Although traditionally classified as asexual, the human fungal pathogen Candida
      albicans can undergo highly efficient mating. A key component of this mating is
      the response to pheromone, which is mediated by a conserved kinase cascade that
      transduces the signal from the pheromone receptor to a transcriptional response
      in the nucleus. In this paper we show (i) that the detailed response of C.
      albicans to the alpha pheromone differs among clinical isolates, (ii) that the
      response depends critically on nutritional conditions, (iii) that the entire
      response is mediated by the Ste2 receptor, and (iv) that, in terms of genes
      induced, the response to alpha pheromone in C. albicans shows only marginal
      overlap with the response in Saccharomyces cerevisiae. We further investigated
      the nutritional control of pheromone induction and identify the GPA2 gene as a
      critical component. We found that Deltagpa2/Deltagpa2 mutants are hypersensitive
      to pheromone and, unlike wild-type strains, show efficient cell cycle arrest
      (including the formation of characteristic halos on solid medium) in response to
      mating pheromone. These results indicate that C. albicans, like several other
      fungal species but unlike S. cerevisiae, integrates signals from a nutrient
      sensing pathway with those of the pheromone response MAP kinase pathway to
      generate the final transcriptional response.

PMID- 16987175
TI  - A new ferrous iron-uptake transporter, EfeU (YcdN), from Escherichia coli.
AB  - Escherichia coli possesses multiple routes for iron uptake. Here we present EfeU
      (YcdN), a novel iron acquisition system of E. coli strain Nissle 1917. Laboratory
      strains of E. coli such as K12 lack a functional (efeU) ycdN gene caused by a
      frameshift mutation. EfeU, a member of the oxidase-dependent iron transporters
      (OFeT), is a homologue of the iron permease Ftr1p from yeast. The ycdN gene is
      part of the ycdNOB tricistronic operon which is expressed in response to iron
      deprivation in a Fur-dependent manner. Expression of efeU resulted in improved
      growth of an E. coli mutant lacking all known iron-uptake systems and mediated
      increased iron uptake into cells. Furthermore, the presence of other divalent
      metal cations did not impair growth of strains expressing efeU. The EfeU protein
      functioned as ferrous iron permease in proteoliposomes in vitro. Topology
      analysis indicated that EfeU is an integral cytoplasmic membrane protein
      exhibiting seven transmembrane helices. Two REXXE motifs within transmembrane
      helices of OFeT family members are implicated in iron translocation. Site
      directed mutagenesis of each REGLE motif of EfeU diminished iron uptake in vivo
      and growth yield. In vitro the EfeU variant protein with an altered first REGLE
      motif was impaired in iron permeation, whereas activity of the EfeU variant with
      a mutation in the second motif was similar to the wild-type protein.

PMID- 16987176
TI  - The peroxisomal import proteins PEX2, PEX5 and PEX7 are differently involved in
      Podospora anserina sexual cycle.
AB  - PEX5, PEX7 and PEX2 are involved in the peroxisomal matrix protein import
      machinery. PEX5 and PEX7 are the receptors for the proteins harbouring,
      respectively, a PTS1 and a PTS2 peroxisomal targeting sequence and cycle between
      the cytoplasm and the peroxisome. PEX2 belongs to the RING-finger complex located
      in the peroxisomal membrane and acts in protein import downstream of PEX5 and
      PEX7; it is therefore required for the import of both PTS1 and PTS2 proteins. We
      have shown previously that PEX2 deficiency leads to an impairment of meiotic
      commitment in the filamentous fungus Podospora anserina. Here we report that both
      PEX5 and PEX7 receptors are dispensable for this commitment but are needed for
      normal sexual cycle. Data suggest also a new role of PEX2 and/or the RING-finger
      complex in addition to their role in PTS1 and PTS2 import. Strikingly, Deltapex5
      and Deltapex7 single and double knockout strains analyses indicate that Deltapex7
      acts as a partial suppressor of Deltapex5 life cycle deficiencies. Moreover,
      contrary to pex2 mutants, Deltapex5 and Deltapex7 show mitochondrial
      morphological abnormalities.

PMID- 16987177
TI  - A novel signal transduction system and feedback loop regulate fructan hydrolase
      gene expression in Streptococcus mutans.
AB  - The fruA gene of Streptococcus mutans encodes for a secreted fructan hydrolase
      (fructanase), an established virulence determinant required for releasing D
      fructose from levan- and inulin-type fructans. Expression of fruA is under the
      control of carbon catabolite repression and is induced by growth in fructans. In
      this report, we identified an operon in S. mutans UA159 encoding a two-component
      system flanked by two predicted carbohydrate-binding proteins that is absolutely
      required for the expression of fruA. All four genes were found to be required for
      optimal growth of S. mutans on inulin-containing medium and for transcriptional
      activation of fruA. Complementation assays using a plasmid expressing the
      response regulator suggested that the two-component system works in concert with
      the sugar-binding proteins. This operon was also shown to activate a four-gene
      cluster located immediately downstream and encoding an Enzyme II (EII(Lev)) for a
      fructose/mannose sugar : phosphotransferase enzyme, which was found to negatively
      regulate the expression of fruA. Using transcriptional fusions, it was found that
      fructose could signal induction of the fruA and levD operons through the two
      component system/sugar-binding protein complex. A recombinant LevR protein was
      shown to bind to the promoter regions of fruA and levD in gel mobility shift
      assays. Thus, a 'four-component signal transduction system' activates fructan
      catabolism and the expression of an Enzyme II complex that functions in a
      feedback loop to sense the accumulation of the end-product of fructan
      degradation.

PMID- 16987178
TI  - Requirement for the acetyl phosphate pathway in Escherichia coli ATP-dependent
      proteolysis.
AB  - Protein degradation is a central component of the protein quality control system.
      Here we show that efficient proteolysis in Escherichia coli requires the active
      acetyl phosphate pathway. Deletion of this pathway, leading to depletion of
      acetyl phosphate, results in temperature sensitivity and reduced rate of ATP
      dependent proteolysis. The effect on proteolysis is general, as can be seen from
      the slowing down of the degradation of unstable proteins, including puromycin
      derived peptides. In addition, reduced intracellular concentrations of acetyl
      phosphate brings about an increase in the levels of protein aggregates, which
      contain a wide range of proteins, as expected if a broad spectrum of substrates
      are involved. Additional outcomes of acetyl phosphate deficiency are elevation in
      the transcript levels of heat shock genes and increased thermotolerance. In E.
      coli the acetyl phosphate pathway is the only source of acetyl phosphate, which
      is a key metabolic compound involved in major cellular processes. In this
      communication we present evidence for the general role of the acetyl phosphate
      pathway in protein degradation.

PMID- 16987179
TI  - The F-box protein Grr1 regulates the stability of Ccn1, Cln3 and Hof1 and cell
      morphogenesis in Candida albicans.
AB  - Both G1 and mitotic cyclins have been implicated in regulating Candida albicans
      filamentous growth. We have investigated the functions of Grr1 whose orthologue
      in Saccharomyces cerevisiae is known to mediate ubiquitin-dependent degradation
      of the G1 cyclins Cln1 and Cln2. Here, we report that deleting C. albicans GRR1
      causes significant stabilization of two G1 cyclins Ccn1 and Cln3 and pseudohyphal
      growth. grr1Delta cells are highly heterogeneous in length and many of them fail
      to separate after cytokinesis. Interestingly, some isolated rod-like G1 cells of
      similar sizes are present in the grr1Delta culture. Time-lapse microscopy
      revealed that the rod-shaped G1 cells first grew exclusively in width before
      budding and then the bud grew exclusively by apical extension until after
      cytokinesis, yielding rod-like daughter cells. Consistently, actin patches
      persistently localize to the bud tip until around the time of cytokinesis.
      Despite the pseudohyphal phenotype, grr1Delta cells respond normally to hyphal
      induction. Hyperphosphorylated Cln3 isoforms accumulate in grr1Delta cells,
      indicating that Grr1 selectively mediates their degradation in wild-type cells.
      grr1Delta pseudohyphal growth requires neither Hgc1 nor Swel, two important
      regulators of cell morphogenesis. Furthermore, the cellular level of Hof1, a
      protein having a role in cytokinesis, is also significantly increased in
      grr1Delta cells.

PMID- 16987180
TI  - Type IV pili-mediated secretion modulates Francisella virulence.
AB  - Francisella tularensis are the causative agent of the zoonotic disease,
      tularaemia. Among four F. tularensis subspecies, ssp. novicida (F. novicida) is
      pathogenic only for immunocompromised individuals, while all four subspecies are
      pathogenic for mice. This study utilized proteomic and bioinformatic approaches
      to identify seven F. novicida secreted proteins and the corresponding Type IV
      pilus (T4P) secretion system. The secreted proteins were predicted to encode two
      chitinases, a chitin binding protein, a protease (PepO), and a beta-glucosidase
      (BglX). The transcription of F. novicida pepO and bglX was regulated by the
      virulence regulator MglA. Intradermal infection of mice with F. novicida mutants
      defective in T4P secretion system or PepO resulted in enhanced F. novicida spread
      to systemic sites. Infection with F. novicida pepO mutants also resulted in
      increased neutrophil infiltration into the mouse airways. PepO is a zinc protease
      that is homologous to mammalian endothelin-converting enzyme ECE-1. Therefore,
      secretion of PepO likely results in increased production of endothelin and
      increased vasoconstriction at the infection site in skin that limits the F.
      novicida spread. Francisella human pathogenic strains contain a mutation in pepO
      predicted to abolish its secretion. Loss of PepO function may have contributed to
      evolution of highly virulent Francisellae.

PMID- 16987181
TI  - Progressing professionalism.

PMID- 16987182
TI  - Current perspectives on medical education in China.

PMID- 16987183
TI  - Current perspectives on medical education in China.
AB  - CONTEXT: China has a long tradition of education and medicine. However, limited
      economic conditions and a huge population mean that further development of
      medical education in China must be tailored to meet the country's needs.
      OBJECTIVES: The aim of this paper is to describe current medical education
      practice in China with reference to the general and historical purposes of
      education in China and how they have affected and continue to affect student
      learning. Reference is also made to both Western medicine and traditional Chinese
      medicine. METHODS: It is argued that traditional educational practices in China
      have encouraged rote learning and that creativity is not cultivated. This affects
      the way many Chinese students learn medicine. Since 1949, the Chinese medical
      education system has developed according to its own needs. The current system for
      training medical students is complex, with medical school curricula lasting 3-8
      years. However, medical education reform is taking place and new teaching methods
      are being introduced in some schools. DISCUSSION: Medical education is important
      to China's large population. The undergraduate medical education system is being
      streamlined and national standards are being established. Innovations in medical
      education have recently been encouraged and supported, including the adoption of
      problem-based learning. It is important that the momentum is kept up so that the
      health care of a fifth of the world's population is assured.

PMID- 16987184
TI  - Assessing the mini-Clinical Evaluation Exercise in comparison to a national
      specialty examination.
AB  - PURPOSE: To evaluate the reliability and validity of the Mini-Clinical Evaluation
      Exercise (mini-CEX) for postgraduate year 4 (PGY-4) internal medicine trainees
      compared to a high-stakes assessment of clinical competence, the Royal College of
      Physicians and Surgeons of Canada Comprehensive Examination in Internal Medicine
      (RCPSC IM examination). METHODS: Twenty-two PGY-4 residents at the University of
      British Columbia and the University of Calgary were evaluated, during the 6
      months preceding their 2004 RCPSC IM examination, with a mean of 5.5 mini-CEX
      encounters (range 3-6). Experienced Royal College examiners from each site
      travelled to the alternate university to assess the encounters. RESULTS: The mini
      CEX encounters assessed a broad range of internal medicine patient problems. The
      inter-encounter reliability for the residents' mean mini-CEX overall clinical
      competence score was 0.74. The attenuated correlation between residents' mini-CEX
      overall clinical competence score and their 2004 RCPSC IM oral examination score
      was 0.59 (P = 0.01). CONCLUSION: By examining multiple sources of validity
      evidence, this study suggests that the mini-CEX provides a reliable and valid
      assessment of clinical competence for PGY-4 trainees in internal medicine.

PMID- 16987185
TI  - Evaluation of consent for peer physical examination: students reflect on their
      clinical skills learning experience.
AB  - INTRODUCTION: Early clinical skills teaching often requires students to learn
      through examining one another. This model should acknowledge ethical, practical
      and individual issues, disclosure and identification of abnormalities. Consent to
      peer physical examination (PPE) is usually expected rather than discussed and
      sought. OBJECTIVES: We sought to evaluate a formal written consent process for
      PPE and to explore students' views of this approach. METHOD: A survey tool was
      designed and distributed to all years 2 and 3 students in the Auckland University
      medical programme (2004). Results were analysed using univariate statistics and
      thematic analysis. RESULTS: The response rate was 57% (146/258). Most students
      had read the participant information sheet prior to signing, with 78% giving
      consent. They had not felt coerced and the in-course experience matched the
      'promise'. Comments included: PPE gave insights into the 'patient's world',
      encouraged peer learning and raised some professional issues. More than 95% of
      students took the examination role at least once (less likely if female, P =
      0.002). Some European, Maori and Pacific students never took the role; all Asian
      students did at least once. Students preferred PPE in groups consisting of
      'friends'. The task influenced group composition by sex (P < 0.0001) but not
      ethnicity. DISCUSSION: Students accept and support a formal consent process. PPE
      participation rates are similar to predictions. The experience must match the
      promises made. Formal preparation alone might have produced similar student
      outcomes. Female students are more selective about tasks undertaken. The
      influence of ethnicity and the effect on future behaviour and attitudes needs
      further exploration.

PMID- 16987186
TI  - The effectiveness and reliability of peer-marking in first-year medical students.
AB  - BACKGROUND: Peer-marking has been suggested as a method to enhance self-directed
      learning and reflection, although whether this improves performance is unclear.
      This study evaluated the impact of peer-marking on examination performance and
      investigated its reliability and acceptability to students. METHODS: First-year
      medical students were randomised to peer-marking using a model answer or no
      intervention (control arm). Student scores were compared with tutor-marked
      scores. Two months later, students completed a summative assessment and
      performance was compared between students randomised to peer-marking and the
      control arm. A focus group was held with students in the intervention arm to
      capture their experiences and attitudes. RESULTS: A total of 289 of 568 students
      consented to participate and 147 were randomised to peer-marking (142 controls).
      Students randomised to peer-marking achieved marginally higher examination marks
      (1.5% difference, 95% CI -0.8% to 3.9%, P = 0.19) than controls (adjusting for
      year and in-course assessment), although this may have been due to chance.
      Students were harsher markers than the tutors. Focus group analysis suggested
      that students valued peer-marking, although concerns about passing judgement on a
      colleague's work were expressed. CONCLUSIONS: Peer-marking did not have a
      substantial effect on examination performance, although a modest effect cannot be
      excluded. Students gained insight into examination technique but may not have
      gained deeper knowledge. Given its potential positive educational value, further
      work is required to understand how peer-marking can be used more effectively to
      enhance the learning experience.

PMID- 16987187
TI  - Speed kills? Speed, accuracy, encapsulations and causal understanding.
AB  - BACKGROUND: The role of basic science, which provides causal explanations for
      clinical phenomena in medical education, is poorly understood. Schmidt has
      postulated that expert clinicians maintain this knowledge in 'encapsulated' form,
      indexed by words or phrases describing the processes. In the present paper we
      show that students who learn causal explanations have a more coherent
      understanding of the relation between diseases and clinical features which, in
      turn, influences recognition of words or phrases describing 'encapsulated
      knowledge' and the ability to maintain performance under speeded conditions.
      HYPOTHESES: In comparison to students who simply learn the features of 4
      diagnostic categories, students who learn a causal explanation will: (a)
      recognise words describing encapsulated knowledge more accurately and (b)
      maintain or improve diagnostic performance under speeded conditions. METHODS: Two
      studies were conducted involving 4 'pseudo-endocrinology' diseases and
      undergraduate psychology students. One group learned signs and symptoms alone;
      the second group also learned a causal explanation. In study 1, they were then
      given a recognition memory task. In study 2, they were asked to diagnose new
      cases either (i) as quickly as possible or (ii) taking their time. RESULTS: In
      study 1, while there was no difference in recognising old words (90% versus 91%),
      the causal group was better able to recognise encapsulated and novel consistent
      words (50% versus 41%) (P = 0.02). In study 2 there was an interaction; causal
      students performed better under speeded conditions (71% versus 66%) but worse
      under thoroughness conditions (67% versus 73%), as predicted. CONCLUSIONS: Causal
      understanding leads to more coherent understanding of clinical conditions, which
      in turn leads to expert-like behaviour.

PMID- 16987188
TI  - The effects of a joint vocational training programme for general practitioner and
      occupational health trainees.
AB  - BACKGROUND: General practitioners (GPs) and occupational health physicians (OHPs)
      would like to improve their collaboration. This could be achieved through a joint
      vocational training programme. OBJECTIVE: To assess the social-psychological
      effects of a joint training programme for GP and OHP trainees for the improvement
      of interprofessional collaboration. METHODS: Questionnaires taken before,
      immediately after and 3 months after a 4-day joint training programme; interviews
      18 months after completing the training programme. SETTING: Erasmus Medical
      Centre, department of general practice (ErasmusMC afdeling Huisartsgeneeskunde)
      in collaboration with the Netherlands School of Public and Occupational Health,
      Amsterdam. PARTICIPANTS: A total of 34 GP and 20 OHP trainees following a joint
      training programme. MAIN OUTCOME MEASURES: Social-psychological variables
      (relative position, occupational identification, dependence, trust), evaluation
      of the contacts, influence of contact on medical policy, frequency of contacts,
      knowledge of guidelines for exchange of information. RESULTS QUESTIONNAIRES: GP
      and OHP trainees' knowledge of the guidelines for exchange of information
      increased. GP trainees' trust increased immediately after the training programme;
      3 months later this effect disappeared. INTERVIEWS: The course helped GPs to
      overcome prejudices against OHPs. CONCLUSION: This type of training programme may
      be effective for increasing trust, but the results do not show a long-term
      effect. Knowledge about the guidelines for exchange of information increased and
      remained for a longer period. Educational expertise should be used to improve
      programmes, especially on social-psychological attitudes (such as trust) and
      behaviour.

PMID- 16987189
TI  - Innovative training for new surgical roles--the place of evaluation.
AB  - BACKGROUND: This paper describes the central role of 'external' evaluation,
      provided by an independent researcher, in developing an innovative curriculum for
      new professional roles with surgery. Workforce changes affecting the National
      Health Service provided an opportunity to develop 2 new roles and design training
      programmes to support them. The perioperative specialist practitioner (PSP) role
      was designed from scratch, while surgical care practitioner (SCP) training built
      on existing practice. Training programmes combined formal modules at Imperial
      College London (approximately 48 days over 10 months) with supervised clinical
      practice in each participant's base hospital. Programmes balanced factual
      knowledge, clinical and communication skills, professional issues and personal
      development and used a range of innovative techniques. EVALUATION METHODS: A
      qualitative approach based on a utilisation-focused model monitored the
      development and implementation of 4 pilot PSP and SCP training programmes. A
      total of 124 individual and 48 group interviews were conducted at intervals over
      3 years, sampling course participants, the project team clinical supervisors and
      administrators. An independent researcher collected, analysed and presented data
      at key stages, feeding back findings to the project team as the programmes
      evolved. DISCUSSION: Effective training programmes for new roles can be
      developed, but the process is time-consuming and requires sensitivity. An
      independent evaluator offers great benefits, modulating the collaborative
      partnership between participants and project team. Positive responses (relating
      to content and teaching methods) from our study enabled us to refine a learner
      centred programme. Negative responses often demanded immediate action to address
      important concerns, and evaluation provided early warning. External evaluation
      provides a vital perspective in the development of curricula supporting new
      roles.

PMID- 16987190
TI  - Educational supervisors evaluate the preparedness of graduates from a reformed UK
      curriculum to work as pre-registration house officers (PRHOs): a qualitative
      study.
AB  - INTRODUCTION: In 1996 the University of Liverpool introduced an integrated
      problem-based learning (PBL) medical curriculum incorporating the recommendations
      of Tomorrow's Doctors. This paper investigates whether the PRHO (pre-registration
      house officer) educational supervisors who supervise Liverpool graduates believe
      that the reformed curriculum is producing house officers who have the
      competencies outlined by the General Medical Council. METHODS: Forty-one
      interviews were arranged with a sample of educational supervisors in the Mersey
      Deanery area to ascertain their views on the competencies of Liverpool PRHOs. The
      interviews were tape-recorded, transcribed and analysed. RESULTS: The supervisors
      felt that the PRHOs had been well prepared to work as PRHOs, and compared with
      traditional graduates they were actually better prepared for the job of PRHO.
      They saw the PRHOs as competent communicators with improved clinical skills, who
      had good attitudes, were aware of limitations, were team workers, good at history
      taking and examination and had different approaches to finding information. There
      was a very confusing picture regarding basic knowledge, with some consultants
      expressing concerns, despite saying they had adequate knowledge to work as PRHOs.
      It emerged that there was little consensus about the knowledge base of the
      traditional or PBL graduates or what knowledge level was needed at this stage.
      DISCUSSION: Educational supervisors believe that the reformed curriculum in
      Liverpool is producing competent PRHOs who have been better prepared for the role
      of PRHO than previous graduates. It could be that uncertainty over knowledge base
      may be the price paid for reducing the factual burden and improving preparedness
      for professional practice.

PMID- 16987191
TI  - Quality of clinical supervision as perceived by specialist registrars in a
      university and district teaching hospital.
AB  - BACKGROUND: Clinical supervision promotes the professional development of
      specialist registrars (SpRs). Our objective was to investigate and compare the
      perceived quality of supervision (PQS) in a university teaching hospital (UTH)
      and a district teaching hospital (DTH) and to identify aspects of supervision
      that could be improved. METHODS: The Cleveland Clinic's teaching effectiveness
      instrument (CCTEI) was used to measure the quality of supervision of attending
      doctors. Fifteen items reflecting good teaching ability were rated on a 5-point
      Likert-scale (1-5 = poor-excellent). RESULTS: SpRs rated 47 attending doctors
      using the CCTEI. A total of 416 ratings were obtained. Overall, the mean PQS was
      3.85 (SD = 0.29) in the DTH and 3.56 (SD = 0.44) in the UTH (P = 0.02). A
      significant difference in PQS was found in 6 items. The supervisors in the DTH
      scored better on all these items. The best predictor of PQS was the item
      'Organises time to allow for both teaching and care giving'. CONCLUSIONS:
      Overall, PQS was better in the DTH compared to the UTH. In both settings,
      generating a good learning environment and respecting the autonomy of the SpRs
      scored favourably. Supervisory roles focusing on improving cost-effective
      practice and communicative skills need more emphasis.

PMID- 16987192
TI  - Growth of private medical education in India.
AB  - BACKGROUND: Medical education has grown in India in nearly 6 decades since
      independence, but no quantitative assessment of this growth exists. DISCUSSION:
      We examine the growth of medical education institutions in India, especially in
      the private sector, and their geographical distribution during the period 1950
      2004. We show that the rapid growth in the number of medical colleges in India
      since 1950 has been driven largely by developments in the private sector. The
      private sector, currently accounting for over 45% of medical colleges in India,
      grew by 900% between 1970 and 2004, with the bulk of this growth occurring in the
      richer states. We assess the reasons for these trends and the ensuing equity
      implications. CONCLUSION: The growth of the private medical education sector over
      the last 6 decades is the most dominant feature of the Indian medical education
      landscape.

PMID- 16987193
TI  - The predictive validity of grade point average scores in a partial lottery
      medical school admission system.
AB  - PURPOSE: To ascertain whether the grade point average (GPA) of school-leaving
      examinations is related to study success, career development and scientific
      performance. The problem of restriction of range was expected to be partially
      reduced due to the use of a national lottery system weighted in favour of
      students with higher GPAs. METHOD: We studied the students (n = 398) admitted to
      the Faculty of Medicine, University of Groningen, the Netherlands in 1982 and
      1983. Data concerning drop-out and study progress were derived from the student
      administration. Data about career development were obtained from annual
      interviews with graduates (n = 318) between 1993 and 2000. Literature searches
      yielded data concerning scientific performance. Multiple linear regression and
      logistic regression were used to analyse the data. The variables 'gender' and
      'cohort' and their interaction were included in the analyses to account for
      variation in the general level of the dependent variable and the effect of GPA on
      the dependent variable. RESULTS: GPA scores had no effect on drop-out rate. High
      GPA scores were associated with significantly less time to graduation, more
      chance of a preferred placement for specialist training and higher scientific
      output. GPA was not related to income. Gender differences were found for study
      duration and scientific output. Women graduated earlier and published less.
      CONCLUSION: The GPA of school-leaving examinations was found to be related to
      study success, career development and scientific performance. In this study the
      usual problem of restriction of range was shown to be absent. The weighted
      lottery procedure even resulted in an over-dispersion of candidates relative to
      the applicants. The resulting effect sizes were in agreement with those reported
      in other studies.

PMID- 16987194
TI  - Relevant behavioural and social science for medical undergraduates: a comparison
      of specialist and non-specialist educators.
AB  - AIM: To compare what medical educators who are specialists in the behavioural and
      social sciences and their non-specialist counterparts consider to be core
      concepts that medical graduates should understand. BACKGROUND: Previously
      perceived as 'nice to know' rather than 'need to know', the General Medical
      Council (GMC) now places behavioural and social sciences on the same need-to-know
      basis as clinical and basic sciences. Attempts have been made to identify what
      components of these topics medical students need to know; however, it remains
      unknown if decisions over programme content differ depending on whether or not
      educationalists have specialist knowledge of the behavioural and social sciences.
      METHODS: In a survey of medical educationalists within all UK medical schools,
      respondents were asked to indicate from a comprehensive list of psychological,
      sociological and anthropological concepts what they considered a minimally
      competent graduate should understand. Comparisons were made between the concepts
      identified by specialist behavioural and social science (BSS) educators and those
      without such training. RESULTS: Despite different disciplinary backgrounds, non
      specialist educators largely concurred with BSS specialist educators in the
      concepts they considered tomorrow's doctors should know about. However, among BSS
      specialists there remained disagreement on what BSS content was relevant for
      graduates. Differences reflect specialist knowledge and recognition of the role
      of theoretical underpinning of BSS and reveal gaps in non-specialists knowledge.
      CONCLUSIONS: Educationalists with formal training in the full range of
      behavioural and social sciences should be involved in the development of BSS
      curriculum content at both national and school levels.

PMID- 16987196
TI  - Genesis of the professional-patient relationship in early practical experience:
      qualitative and quantitative study.
AB  - CONTEXT: As a rule, undergraduate medical students experience everyday work in
      health care as spectators. They are not allowed to participate in real-life
      interaction between professionals and patients. We report on an exception to this
      rule. OBJECTIVES: The aim of this study was to examine undergraduate students'
      experiences in developing their first professional-patient relationships on the
      basis of being responsible for the care of patients. METHODS: The study involved
      2 cohorts (2002 and 2003) of medical students, amounting to 503 students. They
      had all worked in hospitals and/or nursing homes for 4 weeks at the end of their
      first year of study. Subsequent to this, they produced a case presentation of
      experiences in this work they perceived as important. These important experiences
      were the focus of our analysis. RESULTS: Five categories of important experiences
      were identified. Four of the 5 categories are logically interrelated in that they
      collectively cover the range of players involved in a caring situation and
      provide student insights into the interaction between these players. The fifth
      category is a heterogeneous residue category. Analysis and quantification of
      these 5 categories reveals a general similarity: students, to an overwhelming
      degree, are concerned with developing patient-centred care. DISCUSSION: If they
      are given real responsibility for patient care, undergraduate medical students,
      of their own accord, tend to develop patient-centred relationships in accordance
      with the principles of the new professionalism, sometimes in opposition to
      institutional and/or collegial constraints.

PMID- 16987195
TI  - Perceptions of professionalism in medicine: a qualitative study.
AB  - PURPOSE: Current guidelines for medical undergraduate education require students
      to develop appropriate attitudes towards professionalism. As much of the
      literature defines professionalism in vague terms--altruism, humanism, excellence
      -few studies have operationalised medical professionalism. This study aims to
      describe the views and experiences individuals have about medical professionalism
      to provide a more comprehensive understanding of medical professionalism.
      METHODS: An interview study of medical educators, medical students, doctors,
      allied health professionals and lay professionals was employed to assess views
      and experiences of professionalism in medicine. Thematic content analysis was
      applied to the resulting transcripts; the data were managed by NUD*IST software.
      RESULTS: Twenty-three people participated. Two types of examples about
      professionalism were provided: conceptual (honest, trustworthy, competent);
      behavioural (communicating effectively, treating patients equally, working in
      teams). Seven themes were elicited from the data: compliance to values, patient
      access, doctor-patient relationship, demeanour, professional management, personal
      awareness and motivation. CONCLUSION: The study provided a description of views
      about medical professionalism. These data allowed for a more thorough
      conceptualisation which should be used to inform measures of medical
      professionalism in order to improve the validity of assessments of medical
      students' attitudes.

PMID- 16987197
TI  - Developing history of medicine in the University of Liverpool medical curriculum
      1995-2005.
AB  - CONTEXT: The University of Liverpool has always been innovative in its approach
      to medical education. The medical faculty's decision to switch to a full problem
      based learning (PBL) medical curriculum from September 1996 represented an
      opportune moment for history of medicine to put a foot in the curricular door.
      DISCUSSION: The history of medicine component was launched with an initial team
      of 3 staff members, although some 16 people have been involved in its development
      and delivery over the 10 years since it began. This paper is an attempt to
      construct and discuss the history of the course over the past decade, examining
      both the proactive and reactive aspects of its evolution, and how it has been
      perceived by students, the university and staff who have taught on it.

PMID- 16987198
TI  - Do the supervision needs of 'clerkship students' change as they become more
      experienced?

PMID- 16987200
TI  - Object color affects identification and repetition priming.
AB  - We investigated the influence of color on the identification of both non-studied
      and studied objects. Participants studied black and white and color photos of
      common objects and memory was assessed with an identification test. Consistent
      with our meta-analysis of prior research, we found that objects were easier to
      identify from color than from black and white photos. We also found substantial
      priming in all conditions, and study-to-test changes in an object's color reduced
      the magnitude of priming. Color-specific priming effects were large for color
      complex objects, but minimal for color-simple objects. The pattern and magnitude
      of priming effects was not influenced either by the extent to which an object
      always appears in the same color (i.e., whether a color is symptomatic of an
      object) or by the object's origin (natural versus fabricated). We discuss the
      implications of our findings for theoretical accounts of object perception and
      repetition priming.

PMID- 16987201
TI  - Experiencing positive affect and negative affect during stress: relationships to
      cardiac reactivity and to facial expressions.
AB  - We examined the relationship between experienced positive/negative affect and
      cardiac reactivity and facial muscle movements during laboratory tasks with
      different demands. Heart rate, respiratory sinus arrhythmia, pre-ejection period,
      and facial electromyography were measured during startle, mental arithmetic,
      reaction time task, and speech task. The results revealed that individuals
      experiencing high levels of positive affect exhibited more pronounced
      parasympathetic, heart rate, and orbicularis oculi reactivity than others.
      Individuals who experienced high levels of negative affects during the tasks
      showed higher corrugator supercilii responses. Men and women showed slightly
      different response patterns. To conclude, cardiac reactivity may be associated
      with positive involvement and enthusiasm in some situations and all reactivity
      should not automatically be considered as potentially pathological.

PMID- 16987202
TI  - Orthogonality is not a panacea: backpropagation and "catastrophic interference".
AB  - Connectionist models with the backpropagation learning rule are said to exhibit
      catastrophic interference (or forgetting) with sequential training. Subsequent
      works showed that interference can be reduced by using orthogonal inputs. This
      study investigated, with a more rigorous assessment method, whether all
      orthogonal inputs lead to comparable extent of interference using three coding
      schemes. The results revealed large differences between the coding schemes. With
      larger networks, dense inputs led to severer interference compared with sparse
      inputs. With smaller networks, all the three schemes led to comparable extent of
      interference. Therefore, this study proved that not all the orthogonal inputs
      cause the same extent of interference, and that severity of interference depends
      on the interaction of the input coding scheme and the network size.

PMID- 16987203
TI  - Optimism as modifier of escalation of commitment.
AB  - To study whether optimism-pessimism modifies escalation of commitment, 52
      undergraduates were told that they had made an unsuccessful investment, then they
      chose to continue or discontinue this investment. Optimism about future returns
      was induced in one group by varying the probability of a successful outcome from
      an initial low to medium, pessimism was induced in another group by varying this
      probability from an initial high to medium. Supporting the assumption of the
      manipulation, the results showed that optimistic participants preferred to
      continue investments whereas pessimistic participants preferred not to. As
      predicted, when the sunk cost increased, optimism led to escalation of
      commitment, whereas pessimism led to de-escalation of commitment. These effects
      were strengthened when probability of a successful outcome was ambiguous.

PMID- 16987205
TI  - The relationship between false confessions and perceptions of parental rearing
      practices.
AB  - The main aim of the study was to investigate the relationship between a history
      of having made a false confession and reported parental rearing practices. It was
      hypothesized that the reporting of rejection and absence of warmth by parents
      would be associated with the making of a false confession. The participants were
      804 college students in Iceland. Each was asked about false confessions made to
      teachers and parents in the past, as well as about false confessions made to the
      police during questioning. The participants completed questionnaires relating to
      perceived parental rearing practices (EMBU), proneness to antisocial behavior
      (the Gough Socialization Scale), personality (EPQ), self-esteem (Rosenberg), and
      compliance (GCS). Only eight participants (1% of those interrogated) claimed to
      have made false confessions to the police, whereas 10% claimed to have made false
      confessions to teachers or parents. False confessions were significantly
      associated with proneness to antisocial behavior and the EMBU Rejection and
      Warmth scales for both fathers and mothers.

PMID- 16987204
TI  - Musculoskeletal pain complaints and performance on cognitive tasks over the adult
      life span.
AB  - The present study aimed at comparing participants with and without self reported
      musculoskeletal pain in a normal population with regard to performance on a range
      of tests for episodic memory, semantic memory, and other cognitive functions and
      to see if expected differences interacted with age. The results showed that
      participants with pain performed worse on a range of tasks as compared to
      participants without pain, and that these differences occurred regardless of age.
      The most robust effects of pain were displayed on tests for vocabulary and
      construction ability as these were the only effects that remained significant
      after controlling for years of education and reported depression in separate
      analyses. When depression and education were controlled for in the same analysis,
      even these effects were eliminated, suggesting interplay between pain, depressive
      status, and educational level in the negative effects on cognitive functioning.

PMID- 16987206
TI  - The Early Numeracy Test in Finnish: children's norms.
AB  - This article concerns psychometric aspects of the Finnish Early Numeracy Test,
      which has been translated from the original Dutch Early Numeracy Test. The
      advantage of the test is that young children's numerical skills can be assessed
      systematically, which was not possible previously in Finland. A norm study was
      conducted in which the test was administered to a representative sample of 1,029
      Finnish children. The reliability and validity results justify the use of the
      test as an early-childhood screening test and in research on number sense. The
      indicative effects of gender, parental professional education, domicile and
      number of siblings are discussed.

PMID- 16987207
TI  - Do self-presentation concerns moderate the relationship between implicit and
      explicit homonegativity measures?
AB  - This study investigated whether the relation between implicit and explicit
      homonegativity measures is affected by self-presentation concerns, since previous
      research in this area has been inconclusive. In Experiment 1, 70 high-school
      students made evaluative ratings of pictures of homosexual and heterosexual
      couples. Self-presentation was manipulated by either instructing participants
      that the study concerned attitudes regarding sexual orientation (socially
      sensitive) or attitudes regarding age (less sensitive). The age-instruction led
      to increased homonegativity but not to a stronger correlation with an Implicit
      Association Test (IAT; Greenwald, McGhee & Schwartz, 1998) with homo/heterosexual
      couples. Concerns regarding the construct validity of the present implementation
      of the IAT were alleviated in Experiment 2, where heterosexual (n= 30) but not
      homosexual (n= 30) participants showed implicit homonegativity. The current
      findings are problematic for the interpretation of low correspondence between
      implicit and explicit attitude measures as being primarily an effect of self
      presentation concerns.

PMID- 16987208
TI  - Associations between volume of alcohol consumption and social status,
      intelligence, and personality in a sample of young adult Danes.
AB  - Relatively few studies have investigated associations between volume of alcohol
      consumption and psychological characteristics in normal samples. A sub-sample,
      comprising 363 men and 331 women between 29 and 34 years of age, was selected
      from the Copenhagen Perinatal Cohort on the basis of perinatal records. The
      sample was divided into four consumption categories: abstainers (including
      occasional drinkers), light, moderate, and risk drinkers. ANOVA and relevant
      contrasts were used to test the significance of differences among consumption
      categories. Both abstaining and risk drinking were associated with low social
      status family background, low education and intelligence. Abstaining was
      associated with low disinhibition and social recognition scores, while risk
      drinking was associated with high neuroticism and, in males, high disinhibition,
      low social recognition, and low achievement scores. Compared with light drinkers,
      a more "carefree" life orientation characterized male moderate drinkers, while
      relatively high scores on anxiety, dysthymia, and somatoform symptom scales
      characterized female moderate drinkers.

PMID- 16987209
TI  - Empathy and viewing the other as a subject.
AB  - Empathy and viewing another person as a subject rather than an object are often
      associated in theoretical contexts, but empirical research of the relation is
      scarce. The purpose of the present research was to investigate the relationship
      between subject/object view and empathy. In Study 1, participants watched film
      clips and indicated their empathy for specific characters in the clips, as well
      as the extent to which they saw these persons as subjects and objects. The
      subject/object view explained some, but not all, of the differences in empathy,
      which raised the question of what else accounts for differences in empathy. A
      second study was conducted to investigate whether the difficulty of the other's
      situation also contributes. In Study 2, another group watched the film clips and
      rated the difficulty of the film character's situations in addition to empathy
      and subject/object view. The results of Study 2 revealed that subject view/object
      and perceived difficulty together explain a substantial part of differences in
      empathy. It was concluded that empathy is evoked primarily when a person in
      difficulty is viewed as a subject.

PMID- 16987210
TI  - The possible benefits of difficulty: how stress can increase and decrease
      subjective well-being.
AB  - This study explores the effects of stress, trauma, coping and growth orientation
      on subjective well-being. Based on cognitive stress theory, it was hypothesized
      that adversity may contribute to increased or decreased well-being, depending on
      the subsequent meaning these experiences are given. Survey data from Norwegian
      UN/NATO veterans (N= 142) showed that stress and well-being were negatively
      associated (r=-0.20, p < 0.05) at the level of zero-order correlations. However,
      a full structural equation model revealed that the effect of stress on well-being
      was mediated positively through a problem-focused coping process combined with a
      growth component. Stress was negatively mediated through an avoidant-focused
      coping process and a distress component. The effect from stress was fully
      mediated in the model. The hypothesis that stress can produce both increased and
      decreased subjective well-being was confirmed.

PMID- 16987211
TI  - Prediction of driving ability after stroke and the effect of behind-the-wheel
      training.
AB  - The aim of this study was to examine the predictive value of a neuropsychological
      test battery relating to an on-the-road driving evaluation and to determine
      whether patients who failed the driving test could improve their driving through
      behind-the-wheel training. Thirty-four stroke patients were compared with 20
      healthy, matched controls. Patients who failed the driving test were offered
      driving practice at a driving school and were then reassessed
      (neuropsychologically and practically). On most of the cognitive tests, patients
      performed significantly less well than control subjects. Almost 50% of the
      controls and the patients failed the driving evaluation. None of the
      neuropsychological tests was able to predict the driving outcome. Of the patients
      who failed the first driving evaluation, 85% passed the second evaluation after
      driving practice. There are few controlled studies focusing on the stroke
      population and the effect of behind-the-wheel training. It is suggested that more
      controlled studies are needed with more homogenous patient-groups and reliable
      and quantitative outcome measures.

PMID- 16987212
TI  - A comparative assessment of the factor structures and psychometric properties of
      the GHQ-12 and the GHQ-20 based on data from a Finnish population-based sample.
AB  - The General Health Questionnaire (GHQ) is a self-report questionnaire designed to
      identify psychological distress. Psychometric properties of two versions of GHQ
      12 and GHQ-20 were assessed in a large population-based sample of Finnish twins,
      ages 22 to 27 (n= 4580). Participants were randomized into two subgroups, namely
      Twin1 (n= 2294) and Twin2 (n= 2286). The GHQ-12 data were assessed using
      Confirmatory Factor Analysis (CFA). The factor structure of the GHQ-20 was first
      assessed with Exploratory Factor Analysis (EFA) in the Twin1 dataset, and the
      results obtained were then subjected to CFA in Twin1 and Twin2 datasets. The CFA
      of the GHQ-12 indicated that the best fit and the simplest solution were provided
      by the three-factor solution in both subpopulations. Analyses of the GHQ-20
      suggested that the four-factor structure was superior to the three-factor model.
      This result is also theoretically justifiable. Compared to the 12-item version,
      GHQ-20 provides additional fourth factor of anhedonia, suggesting some
      discriminative power.

PMID- 16987213
TI  - Failure of nicotine-dependent enhancement of synaptic efficacy at Schaffer
      collateral CA1 synapses of AD11 anti-nerve growth factor transgenic mice.
AB  - Alzheimer's disease is a neurodegenerative disorder characterized by neuronal
      loss associated with a progressive impairment of cognitive functions. Early
      consequences of Alzheimer's disease include deficit of cholinergic signalling in
      particular regions controlling memory processes, such as the cortex and
      hippocampus, and accumulation of beta-amyloid (Abeta) peptide in neuritic
      plaques. The cholinergic system depends for its integrity and function on nerve
      growth factor. Chronic nerve growth factor deprivation in transgenic mice (AD11)
      engineered to produce recombinant neutralizing anti-nerve growth factor
      antibodies leads to progressive age-dependent Alzheimer's-like neurodegenerative
      pathology similar to that found in patients with Alzheimer's disease, associated
      with a selective loss of cholinergic neurones in the basal forebrain. Here we
      show that in the hippocampus of 6-month-old AD11 mice, Abeta aggregates started
      appearing in the CA1 region. The accumulation of Abeta was associated with a loss
      of cholinergic function at CA3-CA1 synapses. Whereas in wild-type mice nicotine
      induced a persistent increase of synaptic efficacy via alpha7 nicotine
      acetylcholine receptors, in AD11 mice this alkaloid failed to modify synaptic
      strength. Moreover, nicotine failed to transiently enhance the frequency of
      spontaneous miniature glutamatergic currents (miniature excitatory postsynaptic
      currents) recorded from CA1 but not from CA3 pyramidal neurones of AD11 mice.
      However, in CA3 principal cells of AD11 mice, the potentiating effect of nicotine
      on miniature excitatory postsynaptic currents was prevented when Abeta peptide 1
      42 was added to the extracellular solution. These data suggest that in AD11 mice,
      Abeta interferes with nicotine acetylcholine receptors at the level of
      presynaptic glutamatergic terminals, inhibiting their function possibly through
      calcium signalling via presynaptic alpha7 nicotine acetylcholine receptors.

PMID- 16987214
TI  - Exercise affects energy metabolism and neural plasticity-related proteins in the
      hippocampus as revealed by proteomic analysis.
AB  - Studies were conducted to evaluate the effect of a brief voluntary exercise
      period on the expression pattern and post-translational modification of multiple
      protein classes in the rat hippocampus using proteomics. An analysis of 80
      protein spots of relative high abundance on two-dimensional gels revealed that
      approximately 90% of the proteins identified were associated with energy
      metabolism and synaptic plasticity. Exercise up-regulated proteins involved in
      four aspects of energy metabolism, i.e. glycolysis, ATP synthesis, ATP
      transduction and glutamate turnover. Specifically, we found increases in fructose
      bisphosphate aldolase C, phosphoglycerate kinase 1, mitochondrial ATP synthase,
      ubiquitous mitochondrial creatine kinase and glutamate dehydrogenase 1. Exercise
      also up-regulated specific synaptic-plasticity-related proteins, the cytoskeletal
      protein alpha-internexin and molecular chaperones (chaperonin-containing TCP-1,
      neuronal protein 22, heat shock 60-kDa protein 1 and heat shock protein 8).
      Western blot was used to confirm the direction and magnitude of change in
      ubiquitous mitochondrial creatine kinase, an enzyme essential for transducing
      mitochondrial-derived ATP to sites of high-energy demand such as the synapse.
      Protein phosphorylation visualized by Pro-Q Diamond fluorescent staining showed
      that neurofilament light polypeptide, glial fibrillary acidic protein, heat shock
      protein 8 and transcriptional activator protein pur-alpha were more intensely
      phosphorylated with exercise as compared with sedentary control levels. Our
      results, together with the fact that most of the proteins that we found to be up
      regulated have been implicated in cognitive function, support a mechanism by
      which exercise uses processes of energy metabolism and synaptic plasticity to
      promote brain health.

PMID- 16987215
TI  - Overexpression of a truncated TrkB isoform increases the proliferation of neural
      progenitors.
AB  - The truncated isoform of TrkB, TrkB.T1, has been shown to be expressed in the
      neurogenic region of rodent brain. TrkB.T1 lacks tyrosine kinase activity and it
      may modify the action of the full-length TrkB. We show here that the full-length
      TrkB and TrkB.T1 are expressed at the same relative expression levels in mouse
      neural progenitor cell cultures. The number of neurosphere-forming progenitors
      was reduced and apoptosis increased in neurospheres generated from mice
      overexpressing TrkB.T1 when compared with wild-type neurospheres. The
      proliferation of the transgenic neural progenitors was increased, as indicated by
      the larger average diameter of spheres (140% of control), the increased cell
      growth in an MTT assay (137% of control) and the faster rate of 3H-thymidine
      incorporation (128% of control) in the transgenic cell cultures than in controls.
      The proliferation of neural progenitors was also increased after lentivirus
      mediated TrkB.T1 overexpression. A significant increase in 3H-thymidine
      incorporation (119% of control) and the average diameter of spheres (112% of
      control) in the TrkB.T1-transduced neurospheres compared with neurospheres
      transduced with the control vectors confirmed the role of TrkB.T1 in
      proliferation of neural progenitor. When induced to differentiate, progenitors
      overexpressing TrkB.T1 generated two to three times more neurons than did wild
      type cells. The increase in the number of neurons correlated with an increase in
      the number of apoptotic cells (two-fold) at these time points. The data indicate
      that changes in the relative expression levels of different TrkB isoforms
      influence the replicative capacity of neural progenitors.

PMID- 16987216
TI  - Hippocampal CA3 pyramidal cells selectively innervate aspiny interneurons.
AB  - The specific connectivity among principal cells and interneurons determines the
      flow of activity in neuronal networks. To elucidate the connections between
      hippocampal principal cells and various classes of interneurons, CA3 pyramidal
      cells were intracellularly labelled with biocytin in anaesthetized rats and the
      three-dimensional distribution of their axon collaterals was reconstructed. The
      sections were double-stained for substance P receptor (SPR)- or metabotropic
      glutamate receptor 1alpha (mGluR-1alpha)-immunoreactivity to investigate
      interneuron targets of the CA3 pyramidal cells. SPR-containing interneurons
      represent a large portion of the GABAergic population, including spiny and aspiny
      classes. Axon terminals of CA3 pyramidal cells contacted SPR-positive interneuron
      dendrites in the hilus and in all hippocampal strata in both CA3 and CA1 regions
      (7.16% of all boutons). The majority of axons formed single contacts (87.5%), but
      multiple contacts (up to six) on single target neurons were also found. CA3
      pyramidal cell axon collaterals innervated several types of morphologically
      different aspiny SPR-positive interneurons. In contrast, spiny SPR-interneurons
      or mGluR-1alpha-positive interneurons in the hilus, CA3 and CA1 regions were
      rarely contacted by the filled pyramidal cells. These findings indicate a strong
      target selection of CA3 pyramidal cells favouring the activation of aspiny
      classes of interneurons.

PMID- 16987218
TI  - Alteration of GABAergic synapses and gephyrin clusters in the thalamic reticular
      nucleus of GABAA receptor alpha3 subunit-null mice.
AB  - Multiple GABAA-receptor subtypes are assembled from alpha, beta and gamma subunit
      variants. GABAA receptors containing the alpha3 subunit represent a minor
      population with a restricted distribution in the CNS. In addition, they
      predominate in monoaminergic neurons and in the nucleus reticularis thalami
      (nRT), suggesting a role in the regulation of cortical function and sleep. Mice
      with a targeted deletion of the alpha3 subunit gene (alpha3(0/0)) are viable and
      exhibit a subtle behavioural phenotype possibly related to dopaminergic
      hyperfunction. Here, we investigated immunohistochemically the consequences of
      the loss of alpha3 subunit for maturation of GABAA receptors and formation of
      GABAergic synapses in the nRT. Throughout postnatal development, the regional
      distribution of the alpha1, alpha2, or alpha5 subunit was unaltered in
      alpha3(0/0) mice and the prominent alpha3 subunit staining of nRT neurons in
      wildtype mice was not replaced. Subcellularly, as seen by double
      immunofluorescence, the alpha3 and gamma2 subunit were clustered at postsynaptic
      sites in the nRT of adult wildtype mice along with the scaffolding protein
      gephyrin. In alpha3(0/0) mice, gamma2 subunit clustering was disrupted and
      gephyrin formed large aggregates localized at the cell surface, but unrelated to
      postsynaptic sites, indicating that nRT neurons lack postsynaptic GABAA receptors
      in mutant mice. Furthermore, GABAergic terminals were enlarged and reduced in
      number, suggesting a partial deficit of GABAergic synapses. Therefore, GABAA
      receptors are required for gephyrin clustering and long-term synapse maintenance.
      The absence of GABAA-mediated transmission in the nRT may have a significant
      impact on the function of the thalamo-cortical loop of alpha3(0/0) mice.

PMID- 16987217
TI  - Lack of localization of 5-HT6 receptors on cholinergic neurons: implication of
      multiple neurotransmitter systems in 5-HT6 receptor-mediated acetylcholine
      release.
AB  - The involvement of the cholinergic system in learning and memory together with
      the cognitive enhancing properties of 5-HT6 receptor antagonists led us to study
      the relationship between 5-HT6 receptors and cholinergic neurotransmission. A
      selective cholinergic lesion, induced by injection of the immunotoxin 192-IgG
      Saporin into the nucleus basalis magnocellularis, failed to alter the density of
      5-HT6 receptor mRNA or protein expression in the deafferentated frontal cortex,
      suggesting that 5-HT6 receptors are not located on cholinergic neurons. The 5-HT6
      receptor antagonist SB-357134 (0.001-1 microM) induced a concentration-dependant
      K+-evoked [3H]acetylcholine (ACh) release in vitro in rat cortical and striatal
      slices, which was blocked by tetrodotoxin. SB-357134, up to 1 microM, stimulated
      glutamate release in cortical and striatal slices. In the cortex, riluzole (1
      microM) blocked the SB-357134-induced K+-stimulated [3H]ACh release, and
      simultaneous administration of MK-801 (1 microM) and SB-357134 (0.05 microM)
      elicited an increase in K+-evoked ACh release. In the striatum, SB-357134, 1
      microM, decreased dopamine release, and the increase in K+-evoked [3H]ACh release
      induced by 5-HT6 receptor blockade was reversed by the D1 receptor antagonist,
      SCH23390 (1 microM). In both the frontal cortex and striatum, bicuculline, 1
      microM, showed no effect on SB-357134-evoked [3H]ACh. These results are discussed
      in terms of neurochemical mechanisms involved in 5-HT6 receptor functions.

PMID- 16987219
TI  - Kv4 channels sensitive to BmTX3 in rat nervous system: autoradiographic analysis
      of their distribution during brain ontogenesis.
AB  - The binding site distribution of sBmTX3, a chemically synthesized toxin
      originally purified from the venom of the scorpion Buthus martensi, was
      investigated in adult and developing rat brain, using patch-clamp experiments and
      quantitative autoradiography. The molecular basis of these sBmTX3 sites was
      analysed by electrophysiology on transient Kv currents recorded in mammalian
      transfected cells. The rapidly activating and inactivating Kv4.1 current was
      inhibited by sBmTX3 (IC50, 105 nM). The inhibition was less effective on Kv4.2
      and Kv4.3 channels and the toxin did not affect other transient currents such as
      Kv1.4 and Kv3.4. The distribution of the 125I-sBmTX3 binding sites was
      heterogeneous, with a 113-fold difference between the highest and the lowest
      densities in adult rat brain. The site density was particularly important in the
      caudate-putamen and accumbens nucleus, thalamus, hippocampal formation and
      cerebellum. The affinity of sBmTX3 remained constant during brain ontogenesis.
      The level of sBmTX3 binding sites was very low in prenatal and postnatal stages
      to postnatal day (P)12 but drastically increased from P15 in the major part of
      the studied structures except in the CA3 hippocampal field where the density was
      very high from P6. Thus, the distribution of sBmTX3 binding sites in rat brain
      and its electrophysiological characteristics suggest that sBmTX3 specifically
      binds to the Kv4 subfamily of K channels.

PMID- 16987220
TI  - Hyperpolarization-activated and cyclic nucleotide-gated cation channel subunit 2
      ion channels modulate synaptic transmission from nociceptive primary afferents
      containing substance P to secondary sensory neurons in laminae I-IIo of the
      rodent spinal dorsal horn.
AB  - We have previously demonstrated that hyperpolarization-activated and cyclic
      nucleotide-gated cation channel subunit 2 (HCN2) is expressed by terminals of
      peptidergic nociceptive primary afferents in laminae I-IIo of the rat spinal
      dorsal horn. In this study, we investigated the possible neurotransmitters and
      postsynaptic targets of these HCN2-expressing primary afferent terminals in the
      superficial spinal dorsal horn by using immunocytochemical methods. We
      demonstrated that HCN2 widely colocalizes with substance P (SP), and that HCN2
      positive terminals that are also immunoreactive for SP form serial close
      appositions with dendrites and perikarya of neurokinin 1 receptor-immunoreactive
      neurons. It was also found that HCN2-immunoreactive terminals are frequently
      apposed to neurons that are immunoreactive for calbindin, micro-opioid receptor
      and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunit
      GluR2, markers for excitatory interneurons. Investigating HCN2 immunoreactivity
      in glutamic acid decarboxylase 65-green fluorescent protein transgenic mice, we
      found that HCN2-positive terminals occasionally also contact cells that contain
      an isoform of glutamic acid decarboxylase (glutamic acid decarboxylase 65), a
      marker for GABAergic inhibitory neurons. Application of ZD7288, an antagonist of
      HCN channels, onto neurons that were recorded in spinal cord slices with whole
      cell patch-clamp electrodes reduced the number of monosynaptic excitatory
      postsynaptic potentials evoked by electrical stimulation of primary afferents at
      nociceptive intensities. The results suggest that HCN2 may contribute to the
      modulation of membrane excitability of SP-containing nociceptive primary afferent
      terminals, may increase the reliability of synaptic transmission from primary
      afferents to secondary sensory neurons and thus may play a role in the fine
      tuning of pain transmission from nociceptive primary afferents to neurons in the
      spinal dorsal horn.

PMID- 16987221
TI  - Induction of parkin expression in the presence of oxidative stress.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative disorders.
      Gene mutations have been found in rare familial forms of PD, with mutations in
      parkin being the most common cause. Oxidative stresses have also been implicated
      as an important contributing factor in the pathogenesis of PD. Currently, there
      is accumulating evidence that parkin may play a role in maintaining mitochondrial
      function and preventing oxidative stress. We demonstrated here that parkin is up
      regulated when SH-SY5Y dopaminergic neuroblastoma cells are exposed to the
      oxidant dopamine. The up-regulation of parkin appeared to be due to
      transcriptional activation as luciferase assays confirmed that specific parkin
      promoter constructs could confer enhanced transcriptional activation in response
      to dopamine. Moreover, this effect was also seen when SH-SY5Y cells were
      subjected to another oxidative stress, 1-methyl-4-phenylpyridinium. In parallel
      with these studies, we also observed similar transcriptional activation of the
      parkin coregulated gene by oxidative stress. This is the first demonstration that
      parkin expression is up-regulated by oxidative stresses and may suggest that this
      might be a general neuroprotective response of parkin to oxidative stresses.

PMID- 16987222
TI  - Kindling-induced alterations in GABAA receptor-mediated inhibition and
      neurosteroid activity in the rat piriform cortex.
AB  - The piriform cortex makes strong interconnections with limbic structures
      (amygdala, entorhinal cortex and hippocampus) that are involved in memory
      processing. These connections have also been implicated in the development of
      temporal lobe epilepsy. However, little is known about how neurones in this
      region may change during seizure genesis. Here we tested the hypothesis that in
      the kindling model of temporal lobe epilepsy GABAA receptor-mediated inhibition
      is altered in the piriform cortex. To do this we performed whole-cell patch-clamp
      recordings in piriform cortex brain slices obtained from non-kindled and amygdala
      kindled adult rats. We found that kindling coincided with an increase in the
      amplitude and duration of miniature inhibitory post-synaptic currents (mIPSCs)
      recorded from non-pyramidal neurones, whereas the mIPSCs occurring on pyramidal
      (excitatory) cells did not change. Non-stationary noise analysis of mIPSCs
      occurring on the non-pyramidal neurones showed that inferred unitary conductance
      of synaptic channels were the same before and after kindling, implying that the
      channel number increased significantly. Immunocytochemical analysis of the
      inhibitory innervation showed that it was also unaltered by seizure induction. We
      also found that the effect of the positive modulator
      tetrahydrodeoxycorticosterone was reduced on the pyramidal neurones after
      kindling. In contrast, the potentiating effects of tetrahydrodeoxycorticosterone
      on non-pyramidal cells were about the same after kindling as in control (sham)
      rats. These data indicate that amygdala kindling causes a shift in the inhibition
      'balance' between the pyramidal and non-pyramidal cells, perhaps leading to the
      disinhibition of pyramidal cells.

PMID- 16987223
TI  - Dopamine action in the substantia nigra pars reticulata: iontophoretic studies in
      awake, unrestrained rats.
AB  - Dopamine (DA) neurons located in the substantia nigra pars compacta release DA
      not only via axonal terminals, affecting neurotransmission within the striatum,
      but also via dendrites, some of which densely protrude into the substantia nigra
      pars reticulata (SNr). Although the interaction of dendritically released DA with
      somatodendritic autoreceptors regulates DA cell activity, released DA may also
      affect SNr neurons. These cells, however, lack postsynaptic DA receptors, making
      it unclear how locally released DA modulates their activity. Although previous
      work in brain slices suggests that DA might modulate the activity of GABA inputs,
      thus affecting SNr neurons indirectly, it remains unclear how increased or
      decreased DA release might affect these cells exposed to normal afferent inputs.
      To explore this issue, we examined the effects of iontophoretic DA and
      amphetamine on SNr neurons in awake, unrestrained rats. DA had no consistent
      effects on SNr cells but amphetamine, known to induce DA release, dose
      dependently inhibited most of them. This effect was blocked by SCH23390, a
      selective D1 receptor blocker, which itself strongly increased neuronal discharge
      rate. As GABA input is a major factor regulating the activity of SNr neurons, our
      data suggest that dendritically released DA, by interacting with D1 receptors on
      striato-nigral and pallido-nigral afferents, is able to decrease this input, thus
      releasing SNr neurons from tonic, GABA-mediated inhibition. Surprisingly, a full
      DA receptor blockade (SCH23390 + eticlopride) did not result in the expected
      increase in SNr discharge rate, suggesting that other mechanisms are responsible
      for behavioral abnormalities following acute disruption of DA transmission.

PMID- 16987224
TI  - Internalization of D2 dopamine receptors is clathrin-dependent and select to
      dendro-axonic appositions in primate prefrontal cortex.
AB  - Much of our knowledge on trafficking of neurotransmitter receptors derives from
      heterologous expression systems and neurons in vitro. Understanding these
      dynamics in vivo for dopamine receptors, and D2 receptors (D2Rs) in particular,
      presents a foremost challenge as their pharmacological manipulation underlies
      antipsychotic medications and drug abuse, which may in turn alter response to
      endogenous dopamine. Here we present the first ultrastructural evidence of
      clathrin-mediated endocytosis of D2Rs or any other neurotransmitter receptor in
      the primate brain. We have captured in situ the insertion of D2Rs in clathrin
      coated membrane pits, resulting in receptor sorting in primary endosomes.
      Endocytosis was specific to nonsynaptic membranes of distal dendrites, and
      virtually absent from larger shafts, spines, axons and perikarya expressing D2Rs.
      The selective association of D2Rs with the clathrin endocytotic pathway of high
      order dendrites identifies a novel substrate for monitoring and adjusting
      dopaminoception, as well as a potent target for dysregulation, and manipulation,
      of D2R signalling in mental illness.

PMID- 16987225
TI  - A potent non-monoaminergic paradoxical sleep inhibitory system: a reverse
      microdialysis and single-unit recording study.
AB  - Using reverse microdialysis and polygraphic recordings in freely moving cats, we
      investigated the effects on sleep-waking states of application of excitatory and
      inhibitory amino acid agonists, cholinergic agonist and monoamines to the
      periaqueductal grey and adjacent mesopontine tegmentum. Single-unit recordings
      during behavioural states were further used to determine the neuronal
      characteristics of these structures. We found that muscimol, a GABAA receptor
      agonist, induced a significant increase in paradoxical sleep (PS) only when
      applied to a dorsocaudal central tegmental field (dcFTC) located just beneath the
      ventrolateral periaqueductal grey. In this structure, both kainic and N-methyl
      aspartic acids caused a dose-dependent increase in wakefulness (W) and decrease
      in both slow-wave sleep (SWS) and PS. Norepinephrine and epinephrine, and to a
      lesser extent histamine, also increased W and decreased SWS and PS, whereas
      serotonin, dopamine and carbachol, a cholinergic agonist, had no effect. Two
      types of neurones were recorded in this structure, those exhibiting a higher rate
      of tonic discharge during both W and PS compared with during SWS, and those
      showing a phasic increase in firing rate during both active W and PS. Both types
      of neurones showed a gradual increase in unit activity during PS. Our study
      demonstrated for the first time that the ventrolateral periaqueductal grey and
      dcFTC play different roles in behavioural state control, that the dcFTC neurones
      are critically involved in the inhibitory mechanisms of PS generation, playing a
      central part in its maintenance, and that these neurones are under the control of
      GABAergic, glutamatergic, adrenergic and histaminergic systems.

PMID- 16987226
TI  - Inducible and neuronal nitric oxide synthases (NOS) have complementary roles in
      recovery sleep induction.
AB  - Sleep homeostasis is the process by which recovery sleep is generated by
      prolonged wakefulness. The molecular mechanisms underlying this important
      phenomenon are poorly understood. We have previously shown that nitric oxide (NO)
      generation increases in the basal forebrain (BF) during sleep deprivation (SD).
      Moreover, both NO synthase (NOS) inhibition and a NO scavenger prevented recovery
      sleep induction, while administration of a NO donor during the spontaneous sleep
      wake cycle increased sleep, indicating that NO is necessary and sufficient for
      the induction of recovery sleep. Next we wanted to know which NOS isoform is
      involved in the production of recovery sleep. Using in vivo microdialysis we
      infused specific inhibitors of NOS into the BF of rats during SD, and found that
      an inhibitor of inducible NOS (iNOS), 1400W, prevented non-rapid eye movement
      (NREM) recovery, while an inhibitor of neuronal NOS (nNOS), L-N-propyl-arginine,
      decreased REM recovery but did not affect NREM recovery. Using immunoblot
      analysis we found that iNOS was not expressed during the spontaneous sleep-wake
      cycle, but was induced by prolonged wakefulness (increased by 278%). A known iNOS
      inducer, lipopolysaccharide, evoked an increase in sleep that closely resembled
      recovery sleep, and its effects were abolished by 1400W. These results suggest
      that the elevation of NO produced by induction of iNOS in the BF during prolonged
      wakefulness is a specific mechanism for producing NREM recovery sleep and that
      the two NOS isoforms have a complementary role in NREM and REM recovery
      induction.

PMID- 16987227
TI  - Dynamic role of kallikrein 6 in traumatic spinal cord injury.
AB  - Kallikrein 6 (K6) is a member of the kallikrein gene family that comprises 15
      structurally and functionally related serine proteases. In prior studies we
      showed that, while this trypsin-like enzyme is preferentially expressed in
      neurons and oligodendroglia of the adult central nervous system (CNS), it is up
      regulated at sites of injury due to expression by infiltrating immune and
      resident CNS cells. Given this background we hypothesized that K6 is a key
      contributor to the pathophysiology of traumatic spinal cord injury (SCI),
      influencing neural repair and regeneration. Examination of K6 expression
      following contusion injury to the adult rat cord, and in cases of human traumatic
      SCI, indicated significant elevations at acute and chronic time points, not only
      at the injury site but also in cord segments above and below. Elevations in K6
      were particularly prominent in macrophages, microglia and reactive astrocytes. To
      determine potential effects of elevated K6 on the regeneration environment, the
      ability of neurons to adhere to and extend processes on substrata which had been
      exposed to recombinant K6 was examined. Limited (1 h) or excess (24 h) K6
      mediated proteolytic digestion of a growth-facilitatory substrate, laminin,
      significantly decreased neurite outgrowth. By contrast, similar hydrolysis of a
      growth-inhibitory substrate, aggrecan, significantly increased neurite extension
      and cell adherence. These data support the hypothesis that K6 enzymatic cascades
      mediate events secondary to spinal cord trauma, including dynamic modification of
      the capacity for axon outgrowth.

PMID- 16987228
TI  - Early-phase of learning enhances communication between brain hemispheres.
AB  - In the somatosensory system, inputs from one side of the body are only
      transmitted to the contralateral primary somatosensory cortex, but both sides of
      the body representation can interact via interhemispheric connections. These
      interactions depend on the behavioural requirements of the animal and its level
      of arousal. During the process of learning, alertness and attention may modify
      the responsiveness of neuronal pathways. We functionally mapped the brains of
      mice by using [14C]2-deoxyglucose (2DG) autoradiography during the first and the
      third session of a classical conditioning paradigm, involving whiskers
      stimulation on one side of the muzzle paired with an aversive or appetitive
      unconditioned stimulus. During the first pairing session, an increased 2DG uptake
      was seen in the barrel cortex of both hemispheres, independently of the type of
      applied unconditioned stimulus. In the third session of the sensory pairing,
      activation of the barrel cortex was solely contralateral, as expected after
      unilateral whisker stimulation. Thus, sensory stimulation directed to one
      cerebral hemisphere during the initial stages of Pavlovian conditioning activates
      the primary sensory area in both hemispheres. These results suggest that during
      the early phase of conditioning, when alertness is presumably strongest, the
      interhemispheric interactions are enhanced.

PMID- 16987229
TI  - Spatial location is accurately tracked by human auditory sensory memory: evidence
      from the mismatch negativity.
AB  - The nature of spatial representation in human auditory cortex remains elusive. In
      particular, although humans can discriminate the locations of sounds as close as
      1-10 degrees apart, such resolution has not been shown in auditory cortex of
      humans or animals. We used the mismatch negativity (MMN) event related brain
      potential to measure the neural response to spatial change in humans in narrow 10
      degree spatial steps. Twelve participants were tested using a dense array EEG
      setup while watching a silent movie and ignoring the sounds. The MMN was reliably
      elicited by infrequent changes of spatial location of sounds in free field. The
      MMN amplitude was linearly related to the degree of spatial change with a
      resolution of at least 10 degrees. These electrophysiological responses occurred
      within a window of 100-200 milliseconds from stimulus onset, and were localized
      to the posterior superior temporal gyrus. We conclude that azimuthal spatial
      displacement is rapidly, accurately and automatically represented in auditory
      sensory memory in humans, at the level of the auditory cortex.

PMID- 16987230
TI  - Concurrent visuomotor behaviour improves form discrimination in a patient with
      visual form agnosia.
AB  - It is now well established that the visual brain is divided into two visual
      streams, the ventral and the dorsal stream. Milner and Goodale have suggested
      that the ventral stream is dedicated for processing vision for perception and the
      dorsal stream vision for action [A.D. Milner & M.A. Goodale (1995) The Visual
      Brain in Action, Oxford University Press, Oxford]. However, it is possible that
      ongoing processes in the visuomotor stream will nevertheless have an effect on
      perceptual processes. This possibility was examined in the present study. We have
      examined the visual form-discrimination performance of the form-agnosic patient
      D.F. with and without a concurrent visuomotor task, and found that her
      performance was significantly improved in the former condition. This suggests
      that the visuomotor behaviour provides cues that enhance her ability to recognize
      the form of the target object. In control experiments we have ruled out
      proprioceptive and efferent cues, and therefore propose that D.F. can, to a
      significant degree, access the object's visuomotor representation in the dorsal
      stream. Moreover, we show that the grasping-induced perceptual improvement
      disappears if the target objects only differ with respect to their shape but not
      their width. This suggests that shape information per se is not used for this
      grasping task.

PMID- 16987234
TI  - Nitric oxide serves as an endogenous regulator of neuronal adenosine A1 receptor
      expression.
AB  - Nitric oxide (NO) radicals are produced during normal cellular function, after
      tissue injury, and in response to immune system activation during infection. The
      transformation of NO to peroxynitrite is essential for mediating some of its
      physiological and/or cytotoxic actions. As the expression of the adenosine A1
      receptor (A1AR) is regulated by oxidative stress, we evaluated the role of NO in
      the regulation of A1AR expression, a G protein-coupled receptor involved in
      cytoprotection in the central nervous system. Administration of the NO donor, S
      nitrosylpenicillamine (SNAP), to pheochromocytoma 12 (PC12) cells increased A1AR
      protein in a time- and dose-dependent manner, with maximal induction observed
      with 20 microm SNAP at 24 h. The response to SNAP was attenuated by the NO
      scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3 oxide (C
      PTIO), and by the inhibition of nuclear factor-kappaB (NF-kappaB), implicating
      this transcription factor in the regulatory process. In addition SNAP also
      increased the degradation of Inhibitory kappaB-alpha (IkappaB-alpha), a marker of
      NF-kappaB activation. Furthermore, the induction of inducible nitric oxide
      synthase (iNOS) by lipopolysaccharide increased A1AR in PC12 cells and in mice,
      whereas the inhibition of NOS activity suppressed this response. We conclude that
      NO, via the activation of NF-kappaB, serves as an endogenous regulator of A1AR,
      and speculate that the induction of the A1AR could counteract the cytotoxicity of
      NO.

PMID- 16987235
TI  - Oxidative stress-triggered unfolded protein response is upstream of intrinsic
      cell death evoked by parkinsonian mimetics.
AB  - Oxidative stress is a key player in a variety of neurodegenerative disorders
      including Parkinson's disease. Widely used as a parkinsonian mimetic, 6
      hydroxydopamine (6-OHDA) generates reactive oxygen species (ROS) as well as
      coordinated changes in gene transcription associated with the unfolded protein
      response (UPR) and apoptosis. Whether 6-OHDA-induced UPR activation is dependent
      on ROS has not yet been determined. The present study used molecular indicators
      of oxidative stress to place 6-OHDA-generated ROS upstream of the appearance of
      UPR markers such as activating transcription factor 3 (ATF3) and phosphorylated
      stress-activated protein kinase (SAPK/JNK) signaling molecules. Antioxidants
      completely blocked 6-OHDA-mediated UPR activation and rescued cells from
      toxicity. Moreover, cytochrome c release from mitochondria was observed after the
      appearance of early UPR markers, suggesting that cellular stress pathways are
      responsible for its release. Mechanistically, the 6-OHDA-induced UPR was
      independent of intracellular calcium changes. Rather, evidence of protein
      oxidation was observed before the expression of UPR markers, suggesting that the
      rapid accumulation of damaged proteins triggered cell stress/UPR. Taken together,
      6-OHDA-mediated cell death in dopaminergic cells proceeds via ROS-dependent UPR
      up-regulation which leads to an interaction with the intrinsic mitochondrial
      pathway and downstream caspase activation.

PMID- 16987236
TI  - Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up
      regulated in the spinal cord of PQBP-1 transgenic mice before onset of
      degeneration.
AB  - Hepatoma-derived growth factor (HDGF) is a nuclear protein homologous to the high
      mobility group B1 family of proteins. It is known to be released from cells and
      to act as a trophic factor for dividing cells. In this study HDGF was increased
      in spinal motor neurons of a mouse model of motor neuron degeneration,
      polyglutamine-tract-binding protein-1 (PQBP-1) transgenic mice, before onset of
      degeneration. HDGF promoted neurite extension and survival of spinal motor
      neurons in primary culture. HDGF repressed cell death of motor neurons after
      facial nerve section in newborn rats in vivo. We also found a significant
      increase in p53 in spinal motor neurons of the transgenic mice. p53 bound to a
      sequence in the upstream of the HDGF gene in a gel mobility shift assay, and
      promoted gene expression through the cis-element in chloramphenicol acetyl
      transfer (CAT) assay. Finally, we found that HDGF was increased in CSF of PQBP-1
      transgenic mice. Collectively, our results show that HDGF is a novel trophic
      factor for motor neurons and suggest that it might play a protective role against
      motor neuron degeneration in PQBP-1 transgenic mice.

PMID- 16987237
TI  - Reduced expression of neuropeptide genes in a genome-wide screen of a secretion
      deficient mouse.
AB  - Activity-dependent changes in synapses rely on functional changes in resident
      proteins and on gene expression. We addressed the relationship between synapse
      activity and the expression of synaptic genes by comparing RNA levels in the
      neocortex of normal mice versus secretion-deficient and therefore synaptically
      silent munc18-1 (mammalian homologue of Caenorhabditis elegans uncoordinated
      locomotion-18) null mutants, using microarray expression analysis, real-time
      quantitative PCR and northern blotting. We hypothesized that genes under the
      control of synaptic activity would be differentially expressed between mutants
      and controls. We found that few synaptic genes were differentially expressed.
      However, most neuropeptide genes with detectable expression on the microarray
      were differentially expressed, being expressed 3-20-fold higher in control
      cortex. Several other secreted proteins were also differentially expressed, but
      genes encoding their receptors and many other synaptic components were not.
      Differential expression was confirmed by real-time quantitative PCR analysis. In
      situ hybridization indicated that the difference in neuropeptide expression was
      uniform and not due to the loss of specific cells in the mutant. In primary
      sensory neurons, which do not depend on synaptic activity for their input, the
      differential expression of neuropeptides was not observed. These data argue
      against a general relationship between the activity of synapses and the
      expression of their resident proteins, but suggest a link between secretion and
      the expression of genes encoding the secreted products.

PMID- 16987238
TI  - Microsphere embolism-induced endothelial nitric oxide synthase expression
      mediates disruption of the blood-brain barrier in rat brain.
AB  - Microsphere embolism (ME)-induced up-regulation of endothelial nitric oxide
      synthase (eNOS) in endothelial cells of brain microvessels was observed 2-48 h
      after ischemia. eNOS induction preceded disruption of the blood-brain barrier
      (BBB) observed 6-72 h after ischemia. In vascular endothelial cells, ME-induced
      eNOS expression was closely associated with protein tyrosine nitration, which is
      a marker of generation of peroxynitrite. Leakage of rabbit IgG from microvessels
      was also evident around protein tyrosine nitration-immunoreactive microvessels.
      To determine whether eNOS expression and protein tyrosine nitration in vascular
      endothelial cells mediates BBB disruption in the ME brain, we tested the effect
      of a novel calmodulin-dependent NOS inhibitor, 3-[2-[4-(3-chloro-2-methylphenyl)
      1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole
      dihydrochloride 3.5 hydrate (DY-9760e), which inhibits eNOS activity and, in
      turn, protein tyrosine nitration. Concomitant with inhibition of protein tyrosine
      nitration in vascular endothelial cells, DY-9760e significantly inhibited BBB
      disruption as assessed by Evans blue (EB) excretion. DY-9760e also inhibited
      cleavage of poly (ADP-ribose) polymerase as a marker of the apoptotic pathway in
      vascular endothelial cells. Taken together with previous evidence in which DY
      9760e inhibited brain edema, ME-induced eNOS expression in vascular endothelial
      cells likely mediates BBB disruption and, in turn, brain edema.

PMID- 16987239
TI  - Interleukin-1beta induces the expression of aquaporin-4 through a nuclear factor
      kappaB pathway in rat astrocytes.
AB  - Interleukin (IL)-1beta is known to play a role in the formation of brain edema
      after various types of injury. Aquaporin (AQP)4 is also reported to be involved
      in the progression of brain edema. We tested the hypothesis that AQP4 is induced
      in response to IL-1beta. We found that expression of AQP4 mRNA and protein was
      significantly up-regulated by IL-1beta in cultured rat astrocytes, and that
      intracerebroventricular administration of IL-1beta increased the expression of
      AQP4 protein in rat brain. The effects of IL-1beta on induction of AQP4 were
      concentration and time dependent. The effects of IL-1beta on AQP4 were mediated
      through IL-1beta receptors because they were abolished by co-incubation with IL-1
      receptor antagonist. It appeared that IL-1beta increased the level of AQP4 mRNA
      without involvement of de novo protein synthesis because cycloheximide, a protein
      synthesis inhibitor, did not inhibit the effects of IL-1beta. Inhibition of the
      nuclear factor-kappaB (NF-kappaB) pathway blocked the induction of AQP4 by IL
      1beta in a concentration-dependent manner. These findings show that IL-1beta
      induces expression of AQP4 through a NF-kappaB pathway without involvement of de
      novo protein synthesis in rat astrocytes.

PMID- 16987240
TI  - Molecular basis of neuroendocrine cell type-specific expression of the
      chromogranin B gene: Crucial role of the transcription factors CREB, AP-2, Egr-1
      and Sp1.
AB  - The molecular basis of neuroendocrine-specific expression of chromogranin B gene
      (Chgb) has remained elusive. Utilizing wild-type and mutant Chgb
      promoter/luciferase reporter constructs, this study established a crucial role
      for the cAMP response element (CRE) box at -102/-95 bp in endocrine [rat
      pheochromocytoma (chromaffin) cell line (PC12) and rat pituitary somatotrope cell
      line (GC)] and neuronal [rat dorsal root ganglion/mouse neuroblastoma hybrid cell
      line (F-11), cortical and hippocampal primary neurons] cells. Additionally, G/C
      rich domains at -134/-127, -125/-117 and -115/-110 bp played especially important
      roles for endocrine-specific expression of the Chgb gene. Co-transfection of
      expression plasmids for CREB, activator protein-2 (transcription factor) (AP-2),
      early growth response protein (transcription factor) (Egr-1) or specificity
      protein 1 (transcription factor) (Sp1) with the Chgb promoter constructs trans
      activated expression of the Chgb gene. Nuclear extracts from either PC12 or F-11
      cells formed specific complexes with the Chgb (-110/-87 bp) (CRE)
      oligonucleotide, which were either supershifted or disrupted by anti-CREB
      antibodies. In addition PC12 nuclear extracts also formed a specific complex with
      a Chgb (-140/-104-bp) oligonucleotide containing three G/C-rich regions, which
      was dose-dependently disrupted by anti-AP-2, anti-Egr-1 or anti-Sp1 antibodies;
      indeed, any one of these three antibodies completely abolished the complex,
      suggesting that all three factors bind the region simultaneously, at least in
      vitro. Chromatin immunoprecipitation assays documented the binding of the
      transcription factors CREB, AP-2, Egr-1 and Sp1 to the chromosomal Chgb gene
      promoter in vivo in PC12 cells within the context of chromatin. We conclude that
      the neuroendocrine-specific expression of Chgb is mediated by the CRE and G/C
      boxes in cis and the transcription factors CREB, AP-2, Egr-1 and Sp1 in trans.

PMID- 16987241
TI  - GLT-1 down-regulation induced by clozapine in rat frontal cortex is associated
      with synaptophysin up-regulation.
AB  - In rat frontal cortex, extracellular levels of glutamate are raised by the anti
      psychotic drug clozapine. We have recently shown that a significant reduction in
      the levels of the glutamate transporter GLT-1 may be one of the mechanisms
      responsible for this elevation. Here we studied whether GLT-1 down-regulation
      induced by chronic clozapine treatment is associated with changes in the
      expression of synaptophysin, synaptosome-associated protein of 25 kDa (SNAP-25)
      and vesicular glutamate transporter 1 (VGLUT1), three major presynaptic proteins
      involved in neurotransmitter release. Quantitative high-resolution confocal
      microscopy studies in vivo showed that GLT-1 down-regulation is closely
      associated with a significant increase in synaptophysin, but not SNAP-25 and
      VGLUT1, expression. This was confirmed in vitro studies, and in western blotting
      studies of synaptophysin, SNAP-25 and VGLUT1. In addition, our results show that,
      following clozapine treatment, synaptophysin expression increases in the very
      cortical regions in which GLT-1 expression is down-regulated. These findings
      suggest that part of the effects of clozapine may be exerted via an action on the
      presynaptic machinery involved in neurotransmitter release.

PMID- 16987242
TI  - Developmentally-regulated expression of tissue-specific splice variant of rat
      vesicular glutamate transporter 1 in retina and pineal gland.
AB  - Three distinct subtypes of vesicular glutamate transporters (VGLUTs) have been
      identified to date that are expressed basically in a cell type-specific manner.
      We have found a splice variant of VGLUT1 mRNA that is expressed almost
      exclusively in photosensitive tissues, i.e. the retina and the pineal gland. The
      variant mRNA, termed VGLUT1v, contains an additional 75 base pair sequence
      derived from part of a second intron (designated as exon IIa) between exons 2 and
      3. The variant accounted for approximately 70% and 25%of VGLUT1 mRNA in the adult
      retina and pineal gland, respectively. The expression of VGLUT1v was
      developmentally regulated in both tissues. Organ culture showed that expression
      of the variant in the retina increased in association with the development of rod
      cells, suggesting that VGLUT1v is expressed in rod cells. In situ hybridization
      with variant-specific probes showed expression of VGLUT1v in the inner segment
      layer of photoreceptor cells. On the other hand, variant expression did not
      parallel the development of rhodopsin-positive cells in the pineal gland. As rod
      cells and pinealocytes are known to release glutamate continuously at ribbon
      synapses, it is possible that the variant has some functional advantage over the
      wild-type transporter in such a specialized manner of glutamate release.

PMID- 16987243
TI  - Sequential phosphorylation of tau protein by cAMP-dependent protein kinase and
      SAPK4/p38delta or JNK2 in the presence of heparin generates the AT100 epitope.
AB  - Microtubule-associated protein tau in a hyperphosphorylated state is the major
      component of the filamentous lesions that define a number of neurodegenerative
      diseases, including Alzheimer's disease, progressive supranuclear palsy,
      corticobasal degeneration, Pick's disease, argyrophilic grain disease and
      frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).
      Previous work has established that the phosphorylation-dependent anti-tau
      antibody AT100 is a specific marker for filamentous tau in adult human brain.
      Here we have identified protein kinases that generate the AT100 epitope in vitro
      and have used them, in conjunction with site-directed mutagenesis of tau, to map
      the epitope. We show that the sequential phosphorylation of recombinant tau by
      cAMP-dependent protein kinase (PKA) and the stress-activated protein kinases
      SAPK4/p38delta or JNK2 generated the AT100 epitope and that this required
      phosphorylation of T212, S214 and T217. Tau protein from newborn, but not adult,
      mouse brain was weakly labelled by AT100. Phosphorylation by PKA and
      SAPK4/p38delta abolished the ability of tau to promote microtubule assembly, but
      failed to influence significantly the heparin-induced assembly of tau into
      filaments.

PMID- 16987244
TI  - Cyclic ADP-ribose is a second messenger in the lipopolysaccharide-stimulated
      activation of murine N9 microglial cell line.
AB  - Lipopolysaccharide, the main component of the cell wall of Gram-negative
      bacteria, is known to activate microglial cells following its interaction with
      the CD14/Toll-like receptor complex (TLR-4). The activation pathway triggered by
      lipopolysaccharide in microglia involves enhanced basal levels of intracellular
      calcium ([Ca2+]i) and terminates with increased generation of
      cytokines/chemokines and nitric oxide. Here we demonstrate that in
      lipopolysaccharide-stimulated murine N9 microglial cells, cyclic ADP-ribose, a
      universal and potent Ca2+ mobiliser generated from NAD+ by ADP-ribosyl cyclases
      (ADPRC), behaves as a second messenger in the cell activation pathway.
      Lipopolysaccharide induced phosphorylation, mediated by multiple protein kinases,
      of the mammalian ADPRC CD38, which resulted in significantly enhanced ADPRC
      activity and in a 1.7-fold increase in the concentration of intracellular cyclic
      ADP-ribose. This event was paralleled by doubling of the basal [Ca2+]i levels,
      which was largely prevented by the cyclic ADP-ribose antagonists 8-Br-cyclic ADP
      ribose and ryanodine (by 75% and 88%, respectively). Both antagonists inhibited,
      although incompletely, functional events downstream of the lipopolysaccharide
      induced microglia-activating pathway, i.e. expression of inducible nitric oxide
      synthase, overproduction and release of nitric oxide and of tumor necrosis factor
      alpha. The identification of cyclic ADP-ribose as a key signal metabolite in the
      complex cascade of events triggered by lipopolysaccharide and eventually leading
      to enhanced generation of pro-inflammatory molecules may suggest a new
      therapeutic target for treatment of neurodegenerative diseases related to
      microglia activation.

PMID- 16987245
TI  - Glial fibrillary acidic protein is a major target of glycoxidative and
      lipoxidative damage in Pick's disease.
AB  - Pick's disease is a subset of fronto-temporal dementia characterised by severe
      atrophy of the temporal and frontal lobes due to marked neuronal loss accompanied
      by astrocytic gliosis enriched in glial acidic protein. The remaining neurones
      have intracytoplasmic inclusions composed of hyperphosphorylated tau, called Pick
      bodies, in addition to hyperphosphorylated tau in astrocytes and
      oligodendrocytes. Gel electrophoresis and western blotting using markers of
      glycoxidation (advanced glycation end products, N-carboxyethyl-lysine and N
      carboxymethyl-lysine: AGE, CEL, CML, respectively) and lipoxidation (4-hydroxy-2
      nonenal: HNE, and malondialdehyde-lysine: MDAL) were used in the frontal and
      occipital cortex in three Pick's disease cases and three age-matched controls. In
      Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were
      observed in the frontal cortex (but not in the occipital cortex) in association
      with increased density of glial acidic protein bands. Bi-dimensional gel
      electrophoresis and western blotting also disclosed increased amounts and numbers
      of glial acidic protein isoforms in the frontal cortex in Pick's disease.
      Moreover, redox proteomics showed glycoxidation, as revealed with anti-CEL
      antibodies and lipoxidation using anti-HNE antibodies, of at least three glial
      acidic protein isoforms. The present results demonstrate that glial acidic
      protein is a target of oxidative damage in the frontal cortex in Pick's disease.

PMID- 16987246
TI  - Aberrant activation of CDK5 is involved in the pathogenesis of OPIDN.
AB  - Exposure to triorthocresyl phosphate (TOCP) may result in a late neurological
      complication, i.e. organophosphate-induced delayed neuropathy (OPIDN). The aim of
      this study was to examine changes in levels of cyclin-dependent kinase 5 (CDK5)
      and of its activator, p35/p25, in the spinal cord of hens treated by TOCP. After
      exposure to a single dose of TOCP, groups of adult hens were examined in 3, 5, 7,
      9, 14, and 18 days after exposure. CDK5, p35/p25 expression and distribution in
      the lumbar spinal cord were evaluated by immunohistochemistry and Western
      blotting. The hens showed signs of OPIDN around day 9 after exposure. The number
      of p (phosphorylated) -CDK5 and p35 positive cells increased significantly. Co
      localization and mislocalization of p-CDK5 and p35/p25 was identified and became
      evident in neurons around the 9th day. Meanwhile, CDK5, p-CDK5, p35, p25 protein
      levels and p25/p35 ratio were increased, and peaked around the 9th day, then
      decreased. Some hens' unilateral common peroneal was treated by roscovitine 3
      days after TOCP exposure. Axonal transport of these nerves was faster than of
      their opposite side and of those simply treated by TOCP. These findings indicate
      aberrant activation of CDK5 may be involved in the pathogenesis of OPIDN.

PMID- 16987247
TI  - Styrylbenzoazole derivatives for imaging of prion plaques and treatment of
      transmissible spongiform encephalopathies.
AB  - Recent prevalence of acquired forms of transmissible spongiform encephalopathies
      (TSEs) has urged the development of early diagnostic measures as well as
      therapeutic interventions. To extend our previous findings on the value of
      amyloid imaging probes for these purposes, styrylbenzoazole derivatives with
      better permeability of blood-brain barrier (BBB) were developed and analyzed in
      this study. The new styrylbenzoazole compounds clearly labeled prion protein
      (PrP) plaques in brain specimens from human TSE in a manner irrespective of
      pathogen strain, and a representative compound BF-168 detected abnormal PrP
      aggregates in the brain of TSE-infected mice when the probe was injected
      intravenously. On the other hand, most of the compounds inhibited abnormal PrP
      formation in TSE-infected cells with IC50 values in the nanomolar range,
      indicating that they represent one of the most potent classes of inhibitor ever
      reported. BF-168 prolonged the lives of mice infected intracerebrally with TSE
      when the compound was given intravenously at the preclinical stage. The new
      compounds, however, failed to detect synaptic PrP deposition and to show pathogen
      independent therapeutic efficacy, similar to the amyloid imaging probes we
      previously reported. The compounds were BBB permeable and non-toxic at doses for
      imaging and treatment; therefore, they are expected to be of practical use in
      human TSE.

PMID- 16987248
TI  - Copper-dependent inhibition of cytochrome c oxidase by Abeta(1-42) requires
      reduced methionine at residue 35 of the Abeta peptide.
AB  - By altering key amino acid residues of the Alzheimer's disease-associated amyloid
      beta peptide, we investigated the mechanism through which amyloid-beta inhibits
      cytochrome c oxidase (EC 1.9.3.1). Native amyloid-beta inhibited cytochrome
      oxidase by up to 65%, and the level of inhibition was determined by the period of
      amyloid-beta ageing before the cytochrome oxidase assay. Substituting tyrosine-10
      with alanine did not affect maximal enzyme inhibition, but the altered peptide
      required a longer period of ageing. By contrast, oxidizing the sulfur of
      methionine-35 to a sulfoxide, or substituting methionine-35 with valine,
      completely abrogated the peptide's inhibitory potential towards cytochrome
      oxidase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis
      revealed that the loss of inhibitory potential towards cytochrome oxidase with
      the methionine-35-altered peptides did not correlate with a substantially
      different distribution of amyloid-beta oligomeric species. Although the amyloid
      beta-mediated inhibition of cytochrome oxidase was completely dependent on the
      presence of divalent Cu2+, it was not supported by monovalent Cu+, and
      experiments with catalase and H2O2 indicated that the mechanism of cytochrome
      oxidase inhibition does not involve amyloid-beta-mediated H2O2 production. We
      propose that amyloid-beta-mediated inhibition of cytochrome oxidase is dependent
      on the peptide's capacity to bind, then reduce Cu2+, and that it may involve the
      formation of a redox active amyloid-beta-methionine radical.

PMID- 16987250
TI  - Failure to support a genetic contribution of AKT1 polymorphisms and altered AKT
      signaling in schizophrenia.
AB  - The protein kinase v-akt murine thymoma viral oncogene homolog (AKT) gene family
      comprises three human homologs that phosphorylate and inactivate glycogen
      synthase kinase 3beta (GSK3beta). Studies have reported the genetic association
      of AKT1 with schizophrenia. Additionally, decreased AKT1 protein expression and
      the reduced phosphorylation of GSK3beta were reported in this disease, leading to
      a new theory of attenuated AKT1-GSK3beta signaling in schizophrenia pathogenesis.
      We have evaluated this theory by performing both genetic and protein expression
      analyses. A family based association test of AKT1 did not show association with
      schizophrenia in Japanese subjects. The expression levels of total AKT, AKT1 and
      phosphorylated GSK3beta detected in the schizophrenic brains from two different
      brain banks also failed to support the theory. In addition, no attenuated AKT
      GSK3beta signaling was observed in the lymphocytes from Japanese schizophrenics,
      contrasting with previous findings. Importantly, we found that the level of
      phosphorylated GSK3beta at Ser9 tended to be inversely correlated with postmortem
      intervals, and that the phosphorylation levels of AKT were inversely correlated
      with brain pH, issues not assessed in the previous study. These data introduce a
      note of caution when estimating the phosphorylation levels of GSK3beta and AKT in
      postmortem brains. Collectively, this study failed to support reduced signaling
      of the AKT-GSK3beta molecular cascade in schizophrenia.

PMID- 16987249
TI  - Effect of chronic hypoglycaemia on glucose concentration and glycogen content in
      rat brain: A localized 13C NMR study.
AB  - While chronic hypoglycaemia has been reported to increase unidirectional glucose
      transport across the blood-brain barrier (BBB) and to increase GLUT1 expression
      at the endothelium, the effect on steady-state brain d-glucose and brain glycogen
      content is currently unknown. Brain glucose and glycogen concentrations were
      directly measured in vivo using localized 13C magnetic resonance spectroscopy
      (MRS) following 12-14 days of hypoglycaemia. Brain glucose content was
      significantly increased by 48%, which is consistent with an increase in the
      maximal glucose transport rate, Tmax, by 58% compared with the sham-treated
      animals. The localized 13C NMR measurements of brain glucose were directly
      validated by comparison with biochemically determined brain glucose content after
      rapid focused microwave fixation (1.4 s at 4 kW). Both in vivo MRS and
      biochemical measurements implied that brain glycogen content was not affected by
      chronic hypoglycaemia, consistent with brain glucose being a major factor
      controlling brain glycogen content. We conclude that the increased glucose
      transporter expression in chronic hypoglycaemia leads to increased brain glucose
      content at a given level of glycaemia. Such increased brain glucose
      concentrations can result in a lowered glycaemic threshold of counter-regulation
      observed in chronic hypoglycaemia.

PMID- 16987251
TI  - MacMARCKS interacts with the metabotropic glutamate receptor type 7 and modulates
      G protein-mediated constitutive inhibition of calcium channels.
AB  - We have previously shown that the interaction of Ca2+/calmodulin with the
      metabotropic glutamate receptor type 7 (mGluR7) promotes the G-protein-mediated
      inhibition of voltage-sensitive Ca2+ channels (VSCCs) seen upon agonist
      activation. Here, we performed a yeast two-hybrid screen of a new-born rat brain
      cDNA library using the cytoplasmic C-terminal tail of mGluR7 as bait and
      identified macrophage myristoylated alanine-rich c-kinase substrate (MacMARCKS)
      as a binding protein. The interaction was confirmed in vitro and in vivo by pull
      down assays, immunoprecipitation, and colocalization of mGluR7 and MacMARCKS in
      transfected HEK293 cells and cultured cerebellar granule cells. Binding of
      MacMARCKS to mGluR7 was antagonized by Ca2+/calmodulin. In neurons,
      cotransfection of MacMARCKS with mGluR7, but not mGluR7 mutants unable to bind
      MacMARCKS, reduced the G-protein-mediated tonic inhibition of VSCCs in the
      absence of mGluR7 agonist. These results suggest that competitive interactions of
      Ca2+/calmodulin and MacMARCKS with mGluR7 control the tonic inhibition of VSCCs
      by G-proteins.

PMID- 16987252
TI  - Endogenously activated mGlu5 metabotropic glutamate receptors sustain the
      increase in c-Myc expression induced by leukaemia inhibitory factor in cultured
      mouse embryonic stem cells.
AB  - We have shown that endogenous activation of type 5 metabotropic glutamate (mGlu5)
      receptors supports the maintenance of a pluripotent, undifferentiated state in D3
      mouse embryonic stem cells cultured in the presence of leukaemia inhibitory
      factor (LIF). Here, we examined the interaction between LIF and mGlu5 receptors
      using as a read-out the immediate early gene, c-Myc. The selective mGlu5 receptor
      antagonist, 2-methyl-6-(phenylenthynyl)pyridine (MPEP; 1 mum), reduced the
      increase in c-Myc protein levels induced by LIF by enhancing c-Myc
      ubiquitination. A reduction in c-Myc levels was also observed following small
      interfering RNA-mediated mGlu5 receptor gene silencing. MPEP reduced glycogen
      synthase kinase-3beta phosphorylation on Ser9, but increased phosphorylation of
      the phosphatidylinositol-3-kinase (PI-3-K) substrate, AKT. In our hands,
      activated PI-3-K reduced the stability of c-Myc, because (i) the PI-3-K
      inhibitor, LY294002, prevented the reduction in c-Myc levels induced by MPEP; and
      (ii) over-expression of AKT promoted c-Myc ubiquitination. All effects of MPEP
      were mimicked by protein kinase C (PKC) inhibitors and reversed by the PKC
      activator, tetradecanoylphorbol-13-acetate. We conclude that endogenous
      activation of mGlu5 receptors sustains the increase in c-Myc induced by LIF in
      embryonic stem cells by inhibiting both glycogen synthase kinase-3beta and PI-3
      K, both effects resulting from the activation of PKC.

PMID- 16987253
TI  - Cannabinoid-serotonin interactions in alcohol-preferring vs. alcohol-avoiding
      mice.
AB  - Because cannabinoid and serotonin (5-HT) systems have been proposed to play an
      important role in drug craving, we investigated whether cannabinoid 1 (CB1) and 5
      HT(1A) receptor ligands could affect voluntary alcohol intake in two mouse
      strains, C57BL/6 J and DBA/2 J, with marked differences in native alcohol
      preference. When offered progressively (3-10% ethanol) in drinking water, in a
      free-choice procedure, alcohol intake was markedly lower (approximately 70%) in
      DBA/2 J than in C57BL/6 J mice. In DBA/2 J mice, chronic treatment with the
      cannabinoid receptor agonist WIN 55,212-2 increased alcohol intake. WIN 55,212-2
      effect was prevented by concomitant, chronic CB1 receptor blockade by rimonabant
      or chronic 5-HT(1A) receptor stimulation by 8-hydroxy-2-(di-n-propylamino)
      tetralin, which, on their own, did not affect alcohol intake. In C57BL/6 J mice,
      chronic treatment with WIN 55,212-2 had no effect but chronic CB1 receptor
      blockade or chronic 5-HT(1A) receptor stimulation significantly decreased alcohol
      intake. Parallel autoradiographic investigations showed that chronic treatment
      with WIN 55,212-2 significantly decreased 5-HT(1A)-mediated [35S]guanosine
      triphosphate-gamma-S binding in the hippocampus of both mouse strains.
      Conversely, chronic rimonabant increased this binding in C57BL/6 J mice. These
      results show that cannabinoid neurotransmission can exert a permissive control on
      alcohol intake, possibly through CB1-5-HT(1A) interactions. However, the
      differences between C57BL/6 J and DBA/2 J mice indicate that such modulations of
      alcohol intake are under genetic control.

PMID- 16987254
TI  - BMPs, FGF8 and Wnts regulate the differentiation of locus coeruleus noradrenergic
      neuronal precursors.
AB  - In the present study, we investigated the involvement of rhombomere 1 patterning
      proteins in the regulation of the major noradrenergic centre of the brain, the
      locus coeruleus. Primary cultures of rat embryonic day 13.5 locus coeruleus were
      treated with fibroblast growth factor-8, noggin and members of the bone
      morphogenetic and Wnt protein families. We show that bone morphogenetic proteins
      2, 5 and 7 increase and noggin decreases the number of tyrosine hydroxylase
      positive locus coeruleus neurons. Interestingly, from all Wnts expressed in the
      first rhombomere by embryonic day 12.5 in the mice, we only found expression of
      wnt5a mRNA in the vicinity of the locus coeruleus. In agreement with this
      finding, from all Wnts studied in vitro, only Wnt5a increased the number of
      tyrosine hydroxylase-positive neurons in locus coeruleus cultures. Finally, we
      also found that fibroblast growth factor-8 increased the number of tyrosine
      hydroxylase-positive cells in locus coeruleus cultures. Neither of the identified
      factors affected the survival of tyrosine hydroxylase-positive locus coeruleus
      noradrenergic neurons or the proliferation of their progenitors or neurogenesis.
      Instead, our results suggest that these patterning signals of rhombomere 1 may
      work to promote the differentiation of noradrenergic progenitors at later stages
      of development.

PMID- 16987255
TI  - Myiasis as a risk factor for prion diseases in humans.
AB  - Prion diseases are transmissible spongiform encephalopathies of humans and
      animals. The oral route is clearly associated with some prion diseases, according
      to the dissemination of bovine spongiform encephalopathy (BSE or mad cow disease)
      in cattle and kuru in humans. However, other prion diseases such as scrapie (in
      sheep) and chronic wasting disease (CWD) (in cervids) cannot be explained in this
      way and are probably more associated with a pattern of horizontal transmission in
      both domestic and wild animals. The skin and mucous membranes are a potential
      target for prion infections because keratinocytes and lymphocytes are susceptible
      to the abnormal infective isoform of the prion protein. Iatrogenic transmission
      of Creutzfeldt-Jakob disease (CJD) was also recognized after corneal transplants
      in humans and scrapie was successfully transmitted to mice after ocular
      instillation of infected brain tissue, confirming that these new routes could
      also be important in prion infections. Some ectoparasites have been proven to
      harbour prion rods in laboratory experiments. Prion rods were identified in both
      fly larvae and pupae; adult flies are also able to express prion proteins. The
      most common causes of myiasis in cattle and sheep, closely related animals with
      previous prion infections, are Hypoderma bovis and Oestrus ovis, respectively.
      Both species of flies present a life cycle very different from human myiasis, as
      they have a long contact with neurological structures, such as spinal canal and
      epidural fat, which are potentially rich in prion rods. Ophthalmomyiases in
      humans is commonly caused by both species of fly larvae worldwide, providing
      almost direct contact with the central nervous system (CNS). The high expression
      of the prion protein on the skin and mucosa and the severity of the inflammatory
      response to the larvae could readily increase the efficiency of transmission of
      prions in both animals and humans.

PMID- 16987256
TI  - The carcinogenicity of smegma: debunking a myth.
AB  - BACKGROUND: Smegma is widely believed to cause penile, cervical and prostate
      cancer. This nearly ubiquitous myth continues to permeate the medical literature
      despite a lack of valid supportive evidence. METHODS: A historical perspective of
      medical ideas pertaining to smegma is provided, and the original studies in both
      animals and humans are reanalysed using the appropriate statistical methods.
      RESULTS: Evidence supporting the role of smegma as a carcinogen is found wanting.
      CONCLUSIONS: Assertions that smegma is carcinogenic cannot be justified on
      scientific grounds.

PMID- 16987257
TI  - Profile of 513 patients with alopecia areata: associations of disease subtypes
      with atopy, autoimmune disease and positive family history.
AB  - BACKGROUND: Several lines of evidence support a genetic component to alopecia
      areata (AA), including differences in patients based on severity of AA,
      associated diseases and family history. OBJECTIVE: We aimed to examine clinical
      and genetic features of patients with AA with a focus on associated diseases,
      especially atopy, and family history of AA in the USA. METHODS: From 1998 to
      2001, 513 patients with AA completed interviews consisting of demographic
      information, patient's medical history, and family history of AA. RESULTS: Forty
      per cent of respondents had alopecia totalis and/or universalis (AT/AU). These
      patients were younger at the age of onset than those with patchy AA (P < 0.001),
      were more likely to have associated autoimmune or atopic disease (P = 0.047),
      most notably atopic dermatitis (P = 0.021) and thyroid disease (P = 0.012). They
      also had a greater number of relatives affected by AA (P < 0.05). CONCLUSIONS:
      Our findings show marked associations between severity of AA, atopic dermatitis,
      thyroid disease and other autoimmune diseases, and extensive family history of
      AA, suggesting two clinically distinct subtypes of AA with the severe subtype
      possibly associated with greater familial autoimmunity. Further research
      exploring the possibility of a genetic basis to explain these clinical findings
      will be helpful in clarifying our understanding of AA, leading to improvements in
      diagnosis and treatment.

PMID- 16987258
TI  - Medical and psychosocial outcome of patients with occupational contact dermatitis
      in Israel.
AB  - BACKGROUND: Although the medical, financial and prognostic factors of
      occupational contact dermatitis (OCD) have been addressed, studies on the social
      outcome of OCD are sparse. OBJECTIVE: To define the medical and psychosocial
      outcome of patients with OCD. METHODS: Workers with OCD were interviewed by
      telephone using a questionnaire that included questions about the occupation,
      dermatological disease, sick leave, present working status and disability claims,
      and questions related to the subjective perceptions of OCD in all areas of
      psychosocial functioning and quality of life. RESULTS: Seventy workers (64.3%
      males and 35.7% females) were interviewed. Forty per cent had stopped working and
      one-third had taken sick leave because of OCD. Forty-seven (67.1%) were currently
      working while 23 (32.8%) were unemployed. Disability compensation was claimed by
      only 41.4% and was received by 24.3%. Eight workers (11.4%) had persistent
      postoccupational dermatitis (PPOD). Loss of employment affected the occupational
      area of the workers' lives (100%), and also interpersonal relationships (45.7%),
      relationships within the family (18.6%), daily functioning (45.7%) and mental
      health (24.3%). CONCLUSIONS: Considerable working time is lost because of
      unemployment or sick leave due to OCD. Only a small proportion of eligible
      patients with OCD apply for disability compensation and an even smaller
      proportion receive it. Our study demonstrates the significance of OCD to the
      psychosocial aspects of workers' lives and emphasizes that the assessment of OCD
      outcome should relate not only to the medical but also to the psychosocial aspect
      of the disease.

PMID- 16987259
TI  - Basal cell carcinoma arising over facial port wine stain: a single-centre
      experience.
AB  - BACKGROUND: A growing number of reports point to a possible connection between
      basal cell carcinoma (BCC) and port wine stain (PWS). Researchers suggest that
      either the elevated temperature induced by the increased dermal vasculature or an
      oncogenic factor produced by the ectatic vessels makes the overlying epidermis
      more susceptible to ultraviolet or ionizing radiation. OBJECTIVE: To check the
      prevalence of BCC in patients with PWS at a large national vascular amomalies
      centre. METHODS: The study group included 68 patients, 44 women and 24 men, with
      facial PWSs. Detailed data were collected on background features, past treatments
      and past exposure to radiation, and a comprehensive physical examination was
      performed. Biopsy samples were taken from suspect lesions for histological study.
      RESULTS: Four patients (5.9%) were found to have histologically proven BCC, 3
      nodular and one multifocal. All had been exposed to radiation during childhood.
      Treatment consisted of excision; there was one recurrence. CONCLUSION: Although
      the co-occurrence of BCC and PWS is probably related to radiation treatment in
      childhood, these findings should alert physicians to regularly examine PWSs for
      cancerous changes, especially in patients at risk.

PMID- 16987260
TI  - Electro-optical synergy (ELOS) technology for nonablative skin rejuvenation: a
      preliminary prospective study.
AB  - BACKGROUND AND OBJECTIVES: In this preliminary prospective study, we evaluated
      the efficacy and safety of nonablative wrinkle treatment using combined
      radiofrequency (RF) and optical energy (Polaris). The dual energy technology of
      Polaris, called ELOS, which stands for electro-optical synergy, uses synchronous
      pulses of bipolar RF current and pulsed visible light (diode laser) delivered in
      the same pulse. MATERIALS AND METHODS: Twenty-four subjects with periorbital and
      perioral wrinkles received six treatments at 4-week intervals with the Polaris WR
      (Syneron, Inc., Israel, 900 nm, max. RF energy 100 J/cm(3), max. laser energy 50
      J/cm(2)). Each treatment consisted of two passes over the treatment area using
      pulsed optical and RF parameters that were determined by the patient's skin
      phenotype and distribution of target chromophores. The follow-up period was 3
      months after the last treatment. RESULTS: Independent scoring of blinded
      photographs showed a wrinkle score improvement of at least 1 (0 = no improvement,
      1 = medium, 2 = good, 3 = excellent improvement) 3 months after the last of six
      treatment sessions. There was no difference between periorbital and perioral
      wrinkle reduction. Fifty-eight per cent (14/24) of the subjects reported a
      notable wrinkle reduction; 16% noted mild to moderate oedema and erythema lasting
      for no more than 1 day. Scarring or pigmentary changes were not detected. The
      average pain score was 0.6 (0 = no pain, 5 = intolerable pain). CONCLUSION:
      Multiple treatments with the Polaris WR produced objective and subjective
      reduction of periorbital and perioral wrinkles. The occurrence of side-effects
      and pain was very low. The clinical effect may be caused by matrix coagulation of
      the deep dermis by the RF and selective thermolysis of blood vessels with the 900
      nm diode laser.

PMID- 16987261
TI  - Comparison of weekly and daily incremental protocols of narrowband ultraviolet B
      phototherapy for psoriasis.
AB  - BACKGROUND: Different protocols have been used for narrowband ultraviolet B (UVB)
      therapy, commonly used in the treatment of psoriasis; however, more effective and
      reliable protocols are still required. OBJECTIVE: The aim of this study was to
      compare the weekly and daily dose increment protocols of narrowband UVB
      phototherapy in psoriasis patients. METHODS: Thirty patients with plaque
      psoriasis underwent narrowband UVB treatment three times a week and 15 patients
      selected consecutively among these patients underwent a weekly (once in three
      treatments) dose increment whereas the remaining 15 patients underwent a daily
      dose increment. Patients were monitored for 10 weeks and evaluated by the
      Psoriasis Area Severity Index (PASI). RESULTS: When the two groups were evaluated
      according to median PASI scores prior to the treatment and during 10 weeks of
      treatment, there was no statistically significant difference between the groups
      (P > 0.05). During the treatment lasting for 10 weeks, four patients in the group
      with a weekly dose increment and three patients in the group with a daily dose
      increment recovered and no statistically significant difference was detected
      between the groups (P > 0.05). The groups were also evaluated according to the
      median cumulative dose. The median cumulative dose was higher in the group with a
      daily dose increment and the difference between the groups was statistically
      significant (P = 0.002). CONCLUSION: The application of daily dose increments was
      no better than that of weekly dose increments in narrowband UVB treatment for
      psoriasis. Therefore, although our results may need to be supported by large
      series studies, we conclude that application of weekly dose increments with a
      lower cumulative dose having the same efficacy is preferred in narrowband UVB
      treatment of psoriasis.

PMID- 16987262
TI  - Quality of life before and 6 weeks after treatment in a dermatological outpatient
      treatment unit.
AB  - BACKGROUND: Dermatological disease affects quality of life to a great extent.
      Treatments are time-consuming and many patients have problems adhering to
      treatment. Attending an outpatient unit regularly during an intensive treatment
      period may enable patients to cope with their illness, adhere to treatment and
      thus improve their quality of life. OBJECTIVE: To study the effect on quality of
      life of 6 weeks of regular treatment in the outpatient unit in the County
      Hospital of Jonkoping, by means of a questionnaire and interviews. METHODS: The
      Dermatology Life Quality Index (DLQI) was distributed to 50 consecutive patients
      with psoriasis, atopic dermatitis or pruritus attending our outpatient treatment
      unit. Nine of the patients were interviewed during treatment about factors that
      might influence their quality of life. RESULTS: The DLQI scores before treatment
      indicated a low quality of life. Women were more affected than men. After 6 weeks
      of treatment there was a clear improvement, with a 57% reduction in the scores.
      The answers from the interviews indicated important areas of concern such as
      withdrawal from public places, adoption of special clothing habits and concern
      about personal relationships. CONCLUSION: Dermatological diseases have an
      important influence on patients' quality of life. Attending an outpatient
      treatment unit was in this series of cases associated with improved quality of
      life as measured with the DLQI.

PMID- 16987263
TI  - The microenvironment of vulvar skin in women with symptomatic and asymptomatic
      herpes simplex virus type 2 (HSV-2) infection.
AB  - BACKGROUND: It is not known why some individuals infected with herpes simplex
      virus type 2 (HSV-2), experience frequent recurrences, while most of those
      infected have a completely silent infection. OBJECTIVE: We wanted to study if
      local factors in the skin could explain this difference. DESIGn 21 HSV-2
      seropositive patients, 10 with history of >8 clinical recurrences a year
      (symptomatics) and 11 without symptoms of genital herpes (asymptomatics) were
      included. All had to answer a questionnaire. With standardised methods, the skin
      temperature, pH, and the skin barrier function, expressed as transepidermal water
      loss (TEWL) and skin capacitance, were measured on labium majus and perineum.
      Culture for bacteria was performed from the same regions. RESULTS AND CONCLUSION:
      No significant differences in terms of pH and skin barrier function were
      registered between symptomatic and asymptomatic patients. Asymptomatic patients
      had a tendency (0.06) to a higher colonisation with lactobacilli on labium majus
      than symptomatic patients.

PMID- 16987264
TI  - Combination of vinblastine and bleomycin as first line therapy in advanced
      classic Kaposi's sarcoma.
AB  - BACKGROUND: Classic KS (CKS) mainly affects elderly people, has an irregular
      course, and is relatively benign for years. However, sometimes the disease may
      progress rapidly and spread to internal organs, thus necessitating systemic
      chemotherapy. We therefore decided to carry out a prospective trial using
      vinblastine and bleomycin, which are active, easy to administer and control, and
      low cost. METHODS: We treated 29 patients affected by CKS with vinblastine i.v.,
      up to 10 mg in combination with bleomycin i.m., 15 IU every 3 weeks. We
      administered a median of seven cycles of therapy. RESULTS: All the 29 enrolled
      patients were evaluated: 21% reached a complete response and 76% had an
      intermediate response. Toxicity was limited. The maximal response was attained in
      a median of 5 months, with a mean duration of 4 months. CONCLUSION: The
      combination of vinblastine and bleomycin achieved a high rate of objective
      responses in a subgroup of elderly and symptomatic patients, without considerable
      toxicity. We recommend the combination as first line chemotherapy for advanced
      CKS.

PMID- 16987265
TI  - The inflammatory response in drug-induced acute urticaria: ultrastructural study
      of the dermal microvascular unit.
AB  - BACKGROUND: Drug exposure is one of the main aetiologies of urticaria and
      represents the second most common cause in acute urticarias. Studies involving
      the ultrastructural aspects of urticaria are relatively rare in the literature.
      Most of the articles published report on skin biopsies of experimentally induced
      urticaria, and acute urticaria has been studied even less from a morphological
      point of view. OBJECTIVES: The aims of this study were to observe ultrastructural
      cell characteristics in five patients with drug-induced acute urticaria and
      possible aspects of the inflammatory skin response. METHODS: Clinical
      manifestations, light microscopy and transmission electron microscopy were
      evaluated. RESULTS: With light microscopy, a mild perivascular lymphocyte
      monocyte infiltrate was observed with few neutrophils and dermal oedema in skin
      biopsies of five patients. With electron microscopy, a mild vascular dilatation
      was observed, with platelets in the lumen and several lymphocytes and dendritic
      cells close to the superficial dermal vessels. Some mast cells appeared normal,
      whereas others were granule-depleted. In some areas, mast cells, lymphocytes and
      satellite dendritic cells were closely associated, as well as some macrophages. A
      significant number of plasma cells, eosinophils and polymorphonuclear neutrophils
      were not observed; however, the presence of lymphocytes and macrophages was
      significant. The epidermis and the dermal-epidermal junction were preserved,
      except for a discrete oedema in keratinocytes. CONCLUSIONS: The ultrastructural
      aspect of drug-induced acute urticaria is similar to that observed in urticaria
      caused by Urtica dioica, intradermal histamine and cold urticaria. The presence
      of the cellular triad with mast cells, dendritic (or satellite) cells and
      lymphocytes suggests a functional interaction of these cells. These findings
      support the possible existence of mechanisms in the dermis that may participate
      in protective and/or injurious vasocentric immune reactions.

PMID- 16987266
TI  - Extracorporeal photochemotherapy in patients with cutaneous T-cell lymphoma: is
      clinical response predictable?
AB  - BACKGROUND: Extracorporeal photochemotherapy (ECP) has been accepted as a
      standard therapy in cutaneous T-cell lymphomas (CTCL), a category of lymphomas
      mainly resistant to conventional therapies. Approximately one half of patients
      demonstrate a reduction in skin affliction by at least 50% within 12 months of
      therapy and are categorized as responders to ECP. Predictive criteria for
      selecting patients who will respond to ECP are lacking. Such criteria would
      however, be of great benefit. OBJECTIVES: This study compared T-cell clonality
      and serum levels of soluble interleukin-2 receptor (sIL-2R), lactate
      dehydrogenase (LD), neopterin, beta2-microglobulin (beta(2)-M) and granzyme B in
      CTCL patients in order to evaluate their potential usefulness as predictive
      markers. PATIENTS/METHODS: Serum and T lymphocytes obtained from 16 patients with
      CTCL receiving ECP treatment were evaluated in an open retrospective study.
      RESULTS: We found no evident correlation between detected T-cell clonality and
      response to ECP. The non-responding group had on average a higher level of serum
      sIL-2R. This difference was significant after 6 and 12 months of therapy, but not
      pretreatment. An individual reduction in serum sIL-2R, neopterin and beta(2)-M
      during a 6-month course of ECP was well correlated to clinical remission.
      CONCLUSIONS: Seven out of 16 patients were classified as responders. Neither T
      cell clonality nor any of the serum markers assessed pretreatment could reliably
      predict the response to ECP treatment. However, the individual relative changes
      in sIL-2R, neopterin and beta(2)-M during 6 months of ECP treatment coherently
      displayed correlation to the clinical response, as assessed after 12 months of
      ECP treatment.

PMID- 16987267
TI  - Clinical features and risk factors for striae distensae in Korean adolescents.
AB  - BACKGROUND: Despite the high prevalence of striae distensae, clinical studies are
      few in number, and their pathophysiology still obscure. OBJECTIVES: To determine
      the prevalence and clinical characteristics of striae distensae that occur in
      Korean adolescents, and to correlate their clinical features with family history,
      other dermatological conditions, and body measurements. METHODS: One hundred and
      fifty-seven healthy Korean students, aged 15 to 17, were studied. A questionnaire
      and physical examination were employed to assess the subjects' past and family
      history, and the distribution, clinical features and severity of striae
      distensae. RESULTS: Striae distensae were present in 131 subjects (83.4%). Ninety
      four (88.2%) of 109 male and 37 (77.1%) of 48 female subjects were affected. The
      striae were white in colour in 69.5% and asymptomatic in most of the subjects.
      They developed at an average age of 13.8 years. Family history was present in 18
      subjects (11.5%). Seborrhoea of the face was positively correlated (P < 0.035)
      with striae distensae, and atopic dermatitis negatively correlated (P < 0.001).
      In both sexes, the buttock was the most prevalent area of striae development,
      followed by the lower back and knee in boys and by the thigh and calf in girls.
      Striae were significantly more common on the thigh of girls and on the knee of
      boys. CONCLUSIONS: Our results indicate that striae distensae are a common skin
      condition that occurs early in puberty regardless of gender, and that they have a
      different anatomical distribution and relationship with body measurements in each
      gender.

PMID- 16987268
TI  - Influence of narrow-band UVB phototherapy on cutaneous microbiota of children
      with atopic dermatitis.
AB  - OBJECTIVE: In the present work, the effect of narrow-band ultraviolet B (UVB)
      phototherapy on a cutaneous microbial population was evaluated in patients with
      atopic dermatitis (AD) and compared with control patients (vitiligo). METHODS:
      Count, isolation and identification of cutaneous microbiota from anticubital
      fossa were performed in 10 controls and 10 AD patients, both submitted to similar
      levels (P > 0.05) of UVB phototherapy (4.3 +/- 0.9 and 4.3 +/- 0.8 accumulated
      joules, respectively). Additionally, Staphylococcus aureus isolates were screened
      for the production of exotoxins. RESULTS: The total and staphylococcal cutaneous
      microbial population levels were higher (P < 0.05) in AD patients than in the
      controls. All these population levels decreased (P < 0.05) for both AD and
      control patients after UVB phototherapy, which also decreased the SCORAD for AD
      patients. All patients with AD and 50% of controls were carriers of S. aureus,
      and harboured the bacteria simultaneously on skin and anterior nares. All of the
      S. aureus strains recovered from AD patient skin produced toxin and the B type
      was the most frequently detected (70%), followed by C (20%) and A (10%) toxins.
      Only 40% of the S. aureus isolates from control patients produced toxin. After
      UVB treatment, microbial population levels of AD patients were similar (P > 0.05)
      to the ones found in control patients before phototherapy, and toxin production
      ability of S. aureus isolates decreased drastically. CONCLUSION: The results of
      the present study show the beneficial effect of UVB phototherapy on AD and
      suggest that this may be attributable not only to reduction of skin surface
      bacteria but also to the suppression of superantigen production from S. aureus.

PMID- 16987269
TI  - Epidemiological and clinical manifestations of patients hospitalized with brown
      recluse spider bite.
AB  - BACKGROUND: Necrotic arachnidism represents a common health problem and standard
      treatments are usually safe and effective. OBJECTIVE: The aim of this study was
      to review documented Loxosceles species spider envenomations and identify the
      natural history of affected patients. METHODS: A retrospective single-centre
      study included 52 patients with necrotic arachnidism hospitalized in the
      dermatology department between 1997 and 2004. We examined the relationship
      between the epidemiological, clinical and laboratory parameters and degree of
      lesion severity, length of hospitalization and time to complete healing. RESULTS:
      The bites occurred predominantly in rural areas, 67% between April and August.
      Only 35% of the patients sought medical care within 24 h post bite. Most bites
      were of the extremities (67%). Time to complete healing ranged from 14 days to
      more than 8 weeks (mean, 4.8 weeks). A marked relationship was found between age,
      comorbidities, lesion severity and time to complete healing (P < 0.01). Duration
      of hospitalization was significantly longer in patients with severe thigh lesions
      (P < 0.02). CONCLUSIONS: Loxosceles species spider bites frequently induce
      necrotic, slowly healing ulcers on the fatty areas of the body. Early,
      appropriate systemic therapy may provide clinical benefit.

PMID- 16987270
TI  - Neu-Laxova syndrome: a case report and review of the literature.
AB  - Neu-Laxova syndrome (NLS) is a rare autosomal recessive syndrome, characterized
      by severe intrauterine growth retardation (IUGR), microcephaly, abnormal brain
      development, oedema and ichthyosis. It was first reported in 1971 by Neu et al.
      (Pediatrics 47: 610-612) and since then no more than 60 cases have been reported.
      A newborn girl delivered from a 29-year-old healthy mother was admitted to
      hospital with a thick membrane covering her body and dismorphic appearance. The
      diagnosis of NLS was made according to characteristic features. The syndrome is
      known to have a poor prognosis and the baby lived for 9 weeks. This case is one
      of the longest living cases of NLS and the fourth case reported from Turkey.

PMID- 16987271
TI  - CD4+/CD56+ haematodermic neoplasm: a preculsor haematological neoplasm that
      frequently first presents in the skin.
AB  - CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is
      an aggressive and rare preculsor hematologic neoplasm recently recognized by the
      WHO-EORTC classification consensus for cutaneous lymphomas. The neoplasm tends to
      affect elderly patients, who usually present with skin lesions but often have a
      disseminated disease, including bone marrow involvement. Although the lesions are
      composed of cells with a lymphoblast-like morphology and an NK-cell phenotype,
      exhibiting a CD4+, CD56+ positive immunophenotype, recent studies support a
      relationship to plasmacytoid dendritic cells. Because of the rarity of this
      disease, we describe two patients suffering a CD4+/CD56+ hematodermic neoplasm.

PMID- 16987272
TI  - Acitretin-induced erythroderma in a psoriatic patient.

PMID- 16987273
TI  - Superficial granulomatous pyoderma: successful treatment with minocycline.

PMID- 16987274
TI  - Vitiligo-like depigmentation as a presenting sign of metastatic melanoma.

PMID- 16987276
TI  - Needling in molluscum contagiosum.

PMID- 16987275
TI  - Successful treatment with topical tacrolimus for oral psoriasis.

PMID- 16987277
TI  - Psoriasis under haemodialysis.

PMID- 16987278
TI  - Lichen striatus in an adult successfully treated with pimecrolimus cream.

PMID- 16987279
TI  - Acropathia ulcero-mutilans acquisita.

PMID- 16987280
TI  - Perifolliculitis capitis abscedens et suffodiens: an unusual case triggered by
      trauma.

PMID- 16987281
TI  - Clear cell acanthoma occurring on the hallux: the first case report.

PMID- 16987282
TI  - Suit PUVA as an effective and safe modality of treatment in guttate psoriasis.

PMID- 16987283
TI  - Carotenoderma and hypercarotenemia: markers for disordered eating habits.

PMID- 16987284
TI  - Cicatricial pemphigoid associated with coeliac disease in a child.

PMID- 16987285
TI  - A case of hereditary hypotrichosis simplex.

PMID- 16987286
TI  - Acute renal failure induced by intravenous acyclovir.

PMID- 16987287
TI  - Bilateral circumscribed epidermal naevi or naevoid hyperkeratosis of areola
      superimposed with naevus comedonicus?

PMID- 16987288
TI  - Lacquer nail.

PMID- 16987289
TI  - Skin cancer in epidermodysplasia verruciformis patients from Brazil.

PMID- 16987290
TI  - Generalized lichen nitidus with Down syndrome.

PMID- 16987291
TI  - Infliximab-induced eczematoid eruption.

PMID- 16987292
TI  - A case of dyskeratosis congenita associated with schizophrenia and two
      malignancies.

PMID- 16987293
TI  - A case of cutaneous ciliated cyst on the umbilicus mimicking omphalomesenteric
      duct cyst and urachal cyst.

PMID- 16987294
TI  - Atypical presentation of Dowling-Degos disease.

PMID- 16987295
TI  - BRAF V599E mutation occurs in Spitz and Reed naevi.

PMID- 16987296
TI  - Two cases of panniculitis complicating Neisseria meningitidis serogroup A and
      Streptococcus pyogenes bacteraemia, respectively.

PMID- 16987297
TI  - Differing activation status and immune effector molecule expression profiles of
      neonatal and maternal lymphocytes in an African population.
AB  - Higher susceptibility of newborns to infections has been attributed to the hypo
      responsiveness of their cellular immune system. Here we compared the activation
      status and expression of cytokines and cytotoxic molecules of cord versus
      maternal peripheral blood mononuclear cells in an African population. Human
      leucocyte antigen-DR was expressed on a lower percentage of cord compared to
      maternal gammadelta and CD3(+) T cells. Similarly, a lower proportion of cord
      versus maternal gammadelta and CD3(+) T cells displayed perforin, granzyme B and
      cytokine activity either ex vivo or following non-specific stimulation in vitro.
      In contrast, comparable proportions of cord and maternal CD94(+) CD3(-) natural
      killer (NK) cells showed perforin and granzyme B expression ex vivo. We conclude
      that cord blood gammadelta and CD3(+) T cells are functionally hypo-responsive as
      reflected by reduced numbers of such cells expressing either an activation
      marker, T helper 1 (Th1) and Th2 cytokines or cytotoxic effector molecules. The
      similarity in numbers of cord and maternal CD94(+) CD3(-) cells expressing
      cytotoxic effector molecules suggests that neonatal Africans' NK cells may be
      functionally mature.

PMID- 16987299
TI  - New policy on disclosures at Health Services Research.

PMID- 16987298
TI  - The natural compound n-butylidenephthalide derived from Angelica sinensis
      inhibits malignant brain tumor growth in vitro and in vivo.
AB  - The naturally-occurring compound, n-butylidenephthalide (BP), which is isolated
      from the chloroform extract of Angelica sinensis (AS-C), has been investigated
      with respect to the treatment of angina. In this study, we have examined the anti
      tumor effects of n-butylidenephthalide on glioblastoma multiforme (GBM) brain
      tumors both in vitro and in vivo. In vitro, GBM cells were treated with BP, and
      the effects of proliferation, cell cycle and apoptosis were determined. In vivo,
      DBTRG-05MG, the human GBM tumor, and RG2, the rat GBM tumor, were injected
      subcutaneously or intracerebrally with BP. The effects on tumor growth were
      determined by tumor volumes, magnetic resonance imaging and survival rate. Here,
      we report on the potency of BP in suppressing growth of malignant brain tumor
      cells without simultaneous fibroblast cytotocixity. BP up-regulated the
      expression of Cyclin Kinase Inhibitor (CKI), including p21 and p27, to decrease
      phosphorylation of Rb proteins, and down-regulated the cell-cycle regulators,
      resulting in cell arrest at the G(0)/G(1) phase for DBTRG-05MG and RG2 cells,
      respectively. The apoptosis-associated proteins were dramatically increased and
      activated by BP in DBTRG-05MG cells and RG2 cells, but RG2 cells did not express
      p53 protein. In vitro results showed that BP triggered both p53-dependent and
      independent pathways for apoptosis. In vivo, BP not only suppressed growth of
      subcutaneous rat and human brain tumors but also, reduced the volume of GBM
      tumors in situ, significantly prolonging survival rate. These in vitro and in
      vivo anti-cancer effects indicate that BP could serve as a new anti-brain tumor
      drug.

PMID- 16987300
TI  - Will choice-based reform work for Medicare? Evidence from the Federal Employees
      Health Benefits Program.
AB  - OBJECTIVE: . To examine the effect of premiums and benefits on the health plan
      choices of older enrollees who choose Federal Employees Health Benefits Program
      (FEHBP) health plans as their primary payer. DATA SOURCES: Administrative
      enrollment data from the Office of Personnel Management (OPM) and plan premiums
      and benefits data taken from the Checkbook Guide to health plans. STUDY DESIGN:
      We estimate individual plan choice models where the choice of health plan is a
      function of out-of-pocket premium, actuarial value, plan attributes, and
      individual characteristics. Plan attributes include plan structure (fee-for
      service/preferred provider organization, point-of-service, or health maintenance
      organization), drug benefit structure, and whether or not the plan covers other
      types of spending such as dental services and diabetic supplies. The models are
      estimated by conditional logit. Our study focuses on three populations that
      currently choose FEHBP as their primary health care coverage and are similar to
      the Medicare population: current employees and retirees who are approaching the
      age of Medicare eligibility (ages 60-64) and current federal employees age 65+.
      Current employees age 65+ are eligible for Medicare, but their FEHBP plan is
      their primary payer. Retirees and employees 60-64 are not yet eligible for
      Medicare but are similar in many respects to recently age-eligible Medicare
      beneficiaries. We also estimate our model for current employees age 55 and
      younger as a comparison group. DATA COLLECTION METHODS: We select a random sample
      of retirees and employees age 60-64, as well as all current employees age 65+,
      from the OPM administrative database for the calendar year 2001. The plan choices
      available to each person are determined by the plans participating in their
      metropolitan statistical area. We match plan premium and attribute information
      from the Checkbook Guide to each plan in the enrollee's list of choices.
      PRINCIPAL FINDINGS: We find that current workers 65+, 60-64, and non-Medicare
      eligible retirees are sensitive to variation in plan premiums. The premium
      elasticities for these groups are similar in magnitude to those of the age 55 and
      under employee group. Older workers and retirees not yet eligible for Medicare
      are willing to pay a substantial amount for plans with open provider networks.
      The willingness to pay for open networks is significantly greater for these
      groups than for younger employees. Willingness to pay for open network plans
      varies significantly by income, but varies little by age within group.
      CONCLUSIONS: Our finding that older workers and non-Medicare eligible retirees
      are sensitive to plan premiums suggests that choice-based reform of Medicare
      would lead to cost-conscious choices by Medicare beneficiaries. However, our
      finding that these groups are willing to pay more for open network plans than
      younger employees suggest that higher risk individuals may migrate toward higher
      benefit, higher cost plans. Our findings on the relationship between income and
      willingness to pay for open network plans suggest that means testing is a viable
      reform for lowering Medicare program costs.

PMID- 16987301
TI  - Crowd-in: the effect of private health insurance markets on the demand for
      Medicaid.
AB  - OBJECTIVE: To investigate the effects of local labor market conditions and the
      availability of employer-sponsored health insurance on exits from the Medicaid
      program. DATA SOURCE: Data for this project come from a unique administrative
      database containing a 2 percent sample of all cases on California's Medicaid
      program in 1987 and a 2 percent sample of all new cases starting each year
      between 1987 and 1995. STUDY DESIGN: The results are estimated using a discrete
      duration model where the monthly exit probability is a function of demographic
      characteristics, local labor market variables, the probability of having employer
      sponsored insurance, and fixed year and county effects. PRINCIPAL FINDINGS:
      Improvements in labor market opportunities (i.e., employment growth, wage growth,
      and increases in the availability of employer-sponsored health insurance) promote
      exits off the Medicaid program. A 2.5 percentage point increase in the
      availability of employer-sponsored insurance leads to a 6 percent increase in the
      probability that a completed spell lasts no more than 2 years. It would take a 2
      percentage point decrease in unemployment rates or a 10 percent increase in
      average quarterly earnings to yield an equivalent increase in the likelihood of
      exiting Medicaid within 2 years. These effects are robust to the inclusion of
      county-level fixed effects and time effects. CONCLUSIONS: Medicaid expenditures
      and caseloads are sensitive to local economic fluctuations and secular trends in
      the availability of health insurance. Continued decreases in employer-based
      health insurance coverage will greatly increase the demand for public insurance
      coverage and the financial pressures on state governments.

PMID- 16987302
TI  - How much risk pooling is there in the individual insurance market?
AB  - OBJECTIVE: To examine how much pooling of risks occurs among potential purchasers
      in the individual market, how much pooling occurs among those who purchase
      coverage, and whether there is greater pooling among longer-term enrollees. DATA
      SOURCES: The data are administrative records for enrollees in individual
      insurance plans in California in 2001, and from a survey of Californians enrolled
      in the individual insurance market and the uninsured. STUDY DESIGN: Logit models
      were estimated for 5 health outcome measures to compare the insured and uninsured
      after adjusting for other factors that affect insurance status and health.
      Multivariate models were also estimated to explore the relationship between
      health and three measures of pooling in the market: plan type, pricing tier, and
      the actuarially adjusted premium paid by the enrollee. PRINCIPAL FINDINGS: Those
      who purchase individual health insurance are in better health than those who
      remain uninsured. On the other hand, a large share of people with health problems
      does obtain individual insurance. The distribution of subscribers across plan
      type and pricing tier varies with their health status. Those in poor health are
      less likely to purchase low benefit plans. There is less separation of risks for
      those who become sick after enrollment based on the measure of pricing tier. The
      distribution of subscribers across plan type for those who have health problems
      at enrollment and those who become sick differs, but so does the distribution of
      those who become sick and those who remain healthy. CONCLUSIONS: Despite small
      differences among the healthy and sick, our results support the conclusion that
      there is considerable risk pooling in the individual market. To some extent, this
      pooling occurs because underwriting happens at the time people enroll and there
      is greater pooling among those who become sick than those who enroll sick. Our
      results however suggest that health savings accounts may further fragment the
      market.

PMID- 16987303
TI  - Cost-sharing for emergency care and unfavorable clinical events: findings from
      the safety and financial ramifications of ED copayments study.
AB  - OBJECTIVE: To evaluate the effect of emergency department (ED) copayment levels
      on ED use and unfavorable clinical events. Data Source/Study Setting. Kaiser
      Permanente-Northern California (KPNC), a prepaid integrated delivery system.
      STUDY DESIGN: In a quasi-experimental longitudinal study with concurrent
      controls, we estimated rates of ED visits, hospitalizations, ICU admissions, and
      deaths associated with higher ED copayments relative to no copayment, using
      Poisson random effects and proportional hazard models, controlling for patient
      characteristics. The study period began in January 1999; more than half of the
      population experienced an employer-chosen increase in their ED copayment in
      January 2000. DATA COLLECTION/EXTRACTION METHODS: Using KPNC automated databases,
      the 2000 U.S. Census, and California state death certificates, we collected data
      on ED visits and unfavorable clinical events over a 36-month period (January 1999
      through December 2001) among 2,257,445 commercially insured and 261,091 Medicare
      insured health system members. PRINCIPAL FINDINGS: Among commercially insured
      subjects, ED visits decreased 12 percent with the $20-35 copayment (95 percent
      confidence interval [CI]: 11-13 percent), and 23 percent with the $50-100
      copayment (95 percent CI: 23-24 percent) compared with no copayment.
      Hospitalizations, ICU admissions, and deaths did not increase with copayments.
      Hospitalizations decreased 4 percent (95 percent CI: 2-6 percent) and 10 percent
      (95 percent CI: 7-13 percent) with ED copayments of $20-35 and $50-100,
      respectively, compared with no copayment. Among Medicare subjects, ED visits
      decreased by 4 percent (95 percent CI: 3-6 percent) with the $20-50 copayments
      compared with no copayment; unfavorable clinical events did not increase with
      copayments, e.g., hospitalizations were unchanged (95 percent CI: -3 percent to
      +2 percent) with $20-50 ED copayments compared with no copayment. CONCLUSIONS:
      Relatively modest levels of patient cost-sharing for ED care decreased ED visit
      rates without increasing the rate of unfavorable clinical events.

PMID- 16987304
TI  - Restrictions on provider access in health plans and socioeconomic status.
AB  - OBJECTIVE: To model the socioeconomic determinants of restrictions on provider
      access and choices in health plans. DATA SOURCES: Data from the 1996-97 Community
      Tracking Study are used. Publicly available enrollee data including enrollee
      reports of health care plan characteristics are linked with restricted use data
      with insurer reports of health plan characteristics. STUDY DESIGN: This is an
      observational study. A mixed multinomial logit model is used to model the
      enrollees' choice between health plans, each plan being treated as a bundle of
      attributes formed from restrictions on provider access. PRINCIPAL FINDINGS: There
      are important differences between the enrollee responses and the insurer reports,
      which may be due to poor information dissemination on the part of health plans
      and/or lack of attention on the part of enrollees. There is no evidence of
      selection into plans with restrictive attributes on the basis of observed health
      status but there is evidence of selection on the basis of race, ethnicity, gender
      and other socioeconomic characteristics. Determinants of plan supply, i.e.,
      employment characteristics, are the most important determinants of plan attribute
      choices. CONCLUSION: The finding suggests that plan designs optimized using
      "objective" knowledge and with the best intentions may not receive favorable
      reviews from enrollees because enrollees have different perceptions of these
      plans.

PMID- 16987305
TI  - Agency and market area factors affecting home health agency supply changes.
AB  - OBJECTIVE: To use the natural experiment created by the Medicare interim payment
      system (IPS) to study supply change behavior of home health agencies (HHAs) in
      local market areas. DATA SOURCES: One hundred percent Medicare home health claims
      for 1996 and 1999, linked with Medicare Provider of Service and Denominator
      files, and the Area Resource File. STUDY DESIGN: Medicare home health care (HHC)
      claims data were used to distinguish HHAs that changed the local market supply of
      Medicare HHC by their market exit or by significant expansion or contraction of
      their geographic service area between 1996 and 1999 from other HHAs. Multinomial
      logit models were estimated to analyze how characteristics of agencies and the
      market areas in which they served were associated with these different agency
      level supply changes. PRINCIPAL FINDINGS: Changes in local HHA supply stemming
      from geographic service area expansions and contractions rivaled those owing to
      agency closures and market entries. Agencies at greater risk of closure and
      service area contraction tended to be smaller, newer, freestanding agencies,
      operating with more visit-intensive practice styles in markets with more
      competitor agencies. Except for having much less visit-intensive practice styles,
      similar attributes characterized agencies that increased local supply through
      service area expansion. CONCLUSIONS: Supply changes by HHAs largely reflected
      rational market responses by agencies to significant changes in financial
      incentives associated with the Medicare IPS. Recently certified agencies were
      among the most dynamic providers. Supply changes were more likely among agencies
      operating in more competitive market environments.

PMID- 16987306
TI  - Impact of alternative interventions on changes in generic dispensing rates.
AB  - OBJECTIVES: To evaluate the effectiveness of four alternative interventions
      (member mailings, advertising campaigns, free generic drug samples to physicians,
      and physician financial incentives) used by a major health insurer to encourage
      its members to switch to generic drugs. METHODS: Using claim-level data from Blue
      Cross Blue Shield of Michigan, we evaluated the success of four interventions
      implemented during 2000-2003 designed to increase the use of generic drugs among
      its members. Around 13 million claims involving seven important classes of drugs
      were used to assess the effectiveness of the interventions. For each intervention
      a control group was developed that most closely resembled the corresponding
      intervention group. Logistic regression models with interaction effects between
      the treatment group (intervention versus control) and the status of the
      intervention (active versus not active) were used to evaluate if the
      interventions had an effect on the generic dispensing rate (GDR). Because the
      mail order pharmacy was considered more aggressive at converting prescriptions to
      generics, separate generic purchasing models were fitted to retail and mail order
      claims. In secondary analyses separate models were also fitted to claims
      involving a new condition and claims refilled for preexisting conditions.
      RESULTS: The interventions did not appear to increase the market penetration of
      generic drugs for either retail or mail order claims, or for claims involving new
      or preexisting conditions. In addition, we found that the ratio of copayments for
      brand name to generic drugs had a large positive effect on the GDR. CONCLUSIONS:
      The interventions did not appear to directly influence the GDR. Financial
      incentives expressed to consumers through benefit designs have a large influence
      on their switching to generic drugs and on the less-costly mail-order mode of
      purchase.

PMID- 16987307
TI  - Effects of family structure on children's use of ambulatory visits and
      prescription medications.
AB  - OBJECTIVE: To examine the effects of family structure, including number of
      parents, number of other children, and number and type of other adults, on office
      visits, emergency room visits, and use of prescription medications by children.
      DATA SOURCE: The Household Component of the 1996-2001 Medical Expenditure Panel
      Survey (MEPS). STUDY DESIGN: The study consisted of a nationally representative
      sample of children 0-17 years of age living in single-mother or two-parent
      families. We used negative binomial regression to model office visits and
      emergency room visits and logistic regression to model the likelihood of
      prescription medication use. Our analyses adjusted for demographic and
      socioeconomic characteristics as well as measures of children's health and
      parental education and child-rearing experience. DATA COLLECTION/EXTRACTION
      METHOD: We combined 1996-2001 MEPS Full Year Consolidated Files and Medical
      Conditions Files. PRINCIPAL FINDINGS: Descriptive data showed that children in
      single-mother families had fewer office visits than children in two-parent
      families; however, the effect of number of parents in the family on children's
      office visits or use of prescription medications was completely explained by
      other explanatory variables. By contrast, children living in families with many
      other children had fewer total and physician office visits and a lower likelihood
      of using a prescription medication than children living in families with no other
      children even after adjusting for other explanatory variables. Children who lived
      with other adults in addition to their parents also had fewer office visits and a
      lower likelihood of using a prescription medication than children who lived only
      with their parents. CONCLUSIONS: Children living in families with many other
      children or with other adults use less ambulatory care and prescription
      medications than their peers. Additional research is needed to determine whether
      these differences in utilization affect children's health.

PMID- 16987308
TI  - Practice characteristics associated with patient-specific receipt of dental
      diagnostic radiographs.
AB  - OBJECTIVE: To quantify the role of practice characteristics in patient-specific
      receipt of dental diagnostic radiographic services. DATA SOURCE/STUDY SETTING:
      Florida Dental Care Study (FDCS). Study Design. The FDCS was a 48-month
      prospective observational cohort study of community-dwelling adults.
      Participants' dentists were asked to complete a questionnaire about their
      practice characteristics. DATA COLLECTION/EXTRACTION METHODS: In-person
      interviews and clinical examinations were conducted at baseline, 24, and 48
      months, with 6-monthly telephone interviews in between. A single multivariate
      (four radiographic service outcomes) multivariable (multiple explanatory
      covariates) logistic regression was used to model service receipts. PRINCIPAL
      FINDINGS: These practice characteristics were significantly associated with
      patient-specific receipt of radiographic services: number of different practices
      attended during follow-up; dentist's rating of how busy the practice was; typical
      waiting time for a new patient examination; practice size; percentage of patients
      that the dentist reported as interested in details about the condition of their
      mouths; percentage of African American patients in the practice; percentage of
      patients in the practice who do not have dental insurance; and dentist's
      agreement with a statement regarding whether patients should be dismissed from
      the practice. Effects had differential magnitudes and directions of effect,
      depending upon radiograph type. CONCLUSIONS: Practice characteristics were
      significantly associated with patient-specific receipt of services. These effects
      were independent of patient-specific disease level and patient-specific
      sociodemographic characteristics, suggesting that practitioners do influence
      receipt of these diagnostic services. These findings are consistent with the
      conclusion that practitioners act in response to a mix of patients' interests,
      economic self-interests, and their own treatment preferences.

PMID- 16987309
TI  - Aggregation and the measurement of health care costs.
AB  - OBJECTIVE: This study evaluated the extent to which the causes of variation in
      health care costs differ by the level at which observations are made. METHODS:
      More than 40 U.S. and international studies providing empirical estimates of the
      sources of variation in health care costs were reviewed and arrayed by size of
      observational units. A simplified graphical analysis demonstrating how estimated
      correlation coefficients change with the level and type of aggregation is
      presented. RESULTS: As the unit of observation becomes larger, association
      between health care costs and health status/morbidity becomes weaker and smaller
      in magnitude, while correlation with income (per capita GDP) becomes stronger and
      larger. Individual expenditure variation within a particular health care system
      is largely due to differences in health status, but across systems, morbidity has
      almost no effect on costs. For nations, differences in per capita income explain
      over 90 percent of the variation in both time series and cross section.
      CONCLUSIONS: Units of observation used for analysis of health care costs must be
      matched to the units at which decision making occurs. The observed pattern of
      empirical results is consistent with a multilevel allocative model incorporating
      aggregate capacity constraints. To the extent that macro constraints determine
      total budgets at the national level, policy interventions at the micro level
      (substitution of generic pharmaceuticals, use of CEA for allocation of
      treatments, controls on construction and technology, etc.) can act to improve
      efficiency, equity and average health status, but will not usually reduce
      aggregate average per capita costs of medical care.

PMID- 16987311
TI  - Provider attitudes toward pay-for-performance programs: development and
      validation of a measurement instrument.
AB  - OBJECTIVE: To develop an instrument for assessing physician attitudes toward
      quality incentive programs, and to assess its reliability and validity. DATA
      SOURCES: Study involved primary data collection. A 40-item paper and pencil
      survey of primary care physicians in Rochester, New York, and Massachusetts was
      conducted between May 2004 and December 2004. Seven-hundred and ninety-eight
      completed questionnaires were received, representing a response rate of 32
      percent (798/2,497). STUDY DESIGN: Based on an extensive review of the literature
      and discussions with experts in the field, we developed a conceptual framework
      representing the features of pay-for-performance (P4P) programs hypothesized to
      affect physician behavior in that context. A draft questionnaire was developed
      based on that conceptual model and pilot tested in three groups of physicians.
      The questionnaire was modified based on the physician feedback, and the revised
      version was distributed to 2,497 primary care physicians affiliated with two of
      the seven sites participating in Rewarding Results, a national evaluation of
      quality target and financial incentive programs. DATA COLLECTION: Respondents
      were randomly divided into a derivation and a validation sample. Exploratory
      factor analysis was applied to the responses of the derivation sample. Those
      results were used to create scales in the validation sample, and these were then
      subjected to multitrait analysis (MTA). One scale representing physicians'
      perception of the impact of P4P on their clinical practice was regressed on the
      other scales as a test of construct validity. PRINCIPAL FINDINGS: Seven
      constructs were identified and demonstrated substantial convergent and
      discriminant validity in the MTA: awareness and understanding, clinical
      relevance, cooperation, unintended consequences, control, financial salience, and
      impact. Internal consistency reliabilities (Cronbach's alpha coefficients) ranged
      from 0.50 to 0.80. A statistically significant 25 percent of the variation in
      perceived impact was accounted for by physician perceptions of the other six
      characteristics of P4P programs. CONCLUSIONS: It is possible to identify and
      measure the key salient features of P4P programs using a valid and reliable 26
      item survey. This instrument may now be used in further studies to better
      understand the impact of P4P programs on physician behavior.

PMID- 16987313
TI  - Addressing measurement error bias in nurse staffing research.
AB  - OBJECTIVE: To assess the extent of measurement error bias due to methods used to
      allocate nursing staff to the acute care inpatient setting and to recommend
      estimation methods designed to overcome this bias. DATA SOURCES/STUDY SETTING:
      Secondary data obtained from the California Office of Statewide Health Planning
      and Development (OSHPD) and the Centers for Medicare and Medicaid Services'
      Healthcare Cost Report Information System for 279 general acute care hospitals
      from 1996 to 2001. STUDY DESIGN: California OSHPD provides detailed nurse
      staffing data for acute care inpatients. We estimate the measurement error and
      the resulting bias from applying different staffing allocation methods. Estimates
      of the measurement errors also allow insights into the best choices for alternate
      estimation strategies. PRINCIPAL FINDINGS: The bias induced by the adjusted
      patient days method (and its modification) is smaller than for other methods, but
      the bias is still substantial: in the benchmark simple regression model, the
      estimated coefficient for staffing level on quality of care is expected to be one
      third smaller than its true value (and the bias is larger in a multiple
      regression model). Instrumental variable estimation, using one staffing
      allocation measure as an instrument for another, addresses this bias, but only
      particular choices of staffing allocation measures and instruments are suitable.
      CONCLUSIONS: Staffing allocation methods induce substantial attenuation bias, but
      there are easily implemented estimation methods that overcome this bias.

PMID- 16987312
TI  - Implementing the Institute of Medicine definition of disparities: an application
      to mental health care.
AB  - OBJECTIVE: In a recent report, the Institute of Medicine (IOM) defines a health
      service disparity between population groups to be the difference in treatment or
      access not justified by the differences in health status or preferences of the
      groups. This paper proposes an implementation of this definition, and applies it
      to disparities in outpatient mental health care. DATA SOURCES: Health Care for
      Communities (HCC) reinterviewed 9,585 respondents from the Community Tracking
      Study in 1997-1998, oversampling individuals with psychological distress, alcohol
      abuse, drug abuse, or mental health treatment. The HCC is designed to make
      national estimates of service use. STUDY DESIGN: Expenditures are modeled using
      generalized linear models with a log link for quantity and a probit model for any
      utilization. We adjust for group differences in health status by transforming the
      entire distribution of health status for minority populations to approximate the
      white distribution. We compare disparities according to the IOM definition to
      other methods commonly used to assess health services disparities. PRINCIPAL
      FINDINGS: Our method finds significant service disparities between whites and
      both blacks and Latinos. Estimated disparities from this method exceed those for
      competing approaches, because of the inclusion of effects of mediating factors
      (such as income) in the IOM approach. CONCLUSIONS: A rigorous definition of
      disparities is needed to monitor progress against disparities and to compare
      their magnitude across studies. With such a definition, disparities can be
      estimated by adjusting for group differences in models for expenditures and
      access to mental health services.

PMID- 16987314
TI  - The Rieske protein from Paracoccus denitrificans is inserted into the cytoplasmic
      membrane by the twin-arginine translocase.
AB  - The Rieske [2Fe-2S] protein (ISP) is an essential subunit of cytochrome bc(1)
      complexes in mitochondrial and bacterial respiratory chains. Based on the
      presence of two consecutive arginines, it was argued that the ISP of Paracoccus
      denitrificans, a Gram-negative soil bacterium, is inserted into the cytoplasmic
      membrane via the twin-arginine translocation (Tat) pathway. Here, we provide
      experimental evidence that membrane integration of the bacterial ISP indeed
      relies on the Tat translocon. We show that targeting of the ISP depends on the
      twin-arginine motif. A strict requirement is established particularly for the
      second arginine residue (R16); conservative replacement of the first arginine
      (R15K) still permits substantial ISP transport. Comparative sequence analysis
      reveals characteristics common to Tat signal peptides in several bacterial ISPs;
      however, there are distinctive features relating to the fact that the presumed
      ISP Tat signal simultaneously serves as a membrane anchor. These differences
      include an elevated hydrophobicity of the h-region compared with generic Tat
      signals and the absence of an otherwise well-conserved '+5'-consensus motif
      lysine residue. Substitution of the +5 lysine (Y20K) compromises ISP export
      and/or cytochrome bc(1) stability to some extent and points to a specific role
      for this deviation from the canonical Tat motif. EPR spectroscopy confirms
      cytosolic insertion of the [2Fe-2S] cofactor. Mutation of an essential cofactor
      binding residue (C152S) decreases the ISP membrane levels, possibly indicating
      that cofactor insertion is a prerequisite for efficient translocation along the
      Tat pathway.

PMID- 16987315
TI  - Quantitative analysis of the experimental O-J-I-P chlorophyll fluorescence
      induction kinetics. Apparent activation energy and origin of each kinetic step.
AB  - Fluorescence induction has been studied for a long time, but there are still
      questions concerning what the O-J-I-P kinetic steps represent. Most studies agree
      that the O-J rise is related to photosystem II primary acceptor (Q(A)) reduction,
      but several contradictory theories exist for the J-I and I-P rises. One problem
      with fluorescence induction analysis is that most work done to date has used only
      qualitative or semiquantitative data analysis by visually comparing traces to
      observe the effects of different chemicals or treatments. Although this method is
      useful to observe major changes, a quantitative method must be used to detect
      more subtle, yet important, differences in the fluorescence induction trace. To
      achieve this, we used a relatively simple mathematical approach to extract the
      amplitudes and half-times of the three major fluorescence induction phases
      obtained from traces measured in thylakoid membranes kept at various
      temperatures. Apparent activation energies (E(A)) were also obtained for each
      kinetic step. Our results show that each phase has a different E(A), with E(A O
      J) <E(A J-I) < E(A I-P), and thus a different origin. The effects of two well
      known chemicals, 3-(3,4-dichlorophenyl)-1,1-dimethylurea, which blocks electron
      transfer to the photosystem II secondary electron acceptor (Q(B)), and
      decylplastoquinone, which acts similarly to endogenous reducible plastoquinones,
      on the quantitative parameters are discussed in terms of the origin of each
      kinetic phase.

PMID- 16987316
TI  - The ethics question--a closer look.

PMID- 16987317
TI  - Glass ionomers and recurrent caries.

PMID- 16987318
TI  - Victorian era esthetic and restorative dentistry: an advertising trade card
      gallery.
AB  - A chief means of print advertising in the Victorian era was the "trade card."
      Innumerable products, companies, and services were highlighted on colorful
      chromolithographic trade cards, and these became desirable collectible objects
      which were pasted into scrapbooks and enjoyed by many families. Dentistry- and
      oral health-related subjects were often depicted on Victorian trade cards, and
      esthetic and restorative dentistry themes were featured. This review describes
      the history of advertising trade cards and offers a photographic gallery of
      dentistry-related cards of the era.

PMID- 16987320
TI  - Clinical evaluation of direct cuspal coverage with posterior composite resin
      restorations.
AB  - BACKGROUND: Composite resins have esthetic properties; they join the ability to
      preserve and reinforce sound tooth structure. Conservation is becoming popular
      for both small to medium defects and more compromised teeth. PURPOSE: This study
      aimed to evaluate the clinical performance of Class II cuspal coverage direct
      composite restorations. MATERIALS AND METHODS: Twenty patients, 18 years or
      older, were included in this clinical trial restoring 25 vital molar teeth with
      one or two missing cusps. Criteria for inclusion are two or three surface
      restorations, replacement of composite and amalgam fillings (secondary decay,
      fracture of either filling material or tooth structure, aesthetic
      considerations), or virgin teeth with decay undermining a cusp. Teeth with
      residual cavity walls less than 1 mm or with complete loss of the clinical crown
      were excluded. Teeth were restored using a combination of Ultra-Etch 35%
      phosphoric acid, PQ1 adhesive system, and Vit-l-escence microhybrid composite
      resin (Ultradent Products, Inc., South Jordan, UT, USA). The enamel peripheral
      skeleton of the restoration was built up first, followed by dentin and enamel
      occlusal surface stratification. Wedge-shaped increments of composite resin were
      placed and cured using the variable intensity polimerizer (VIP) light (Bisco
      Inc., Schaumburg, IL, USA) through a combination of a pulse and progressive
      curing technique. RESULTS: All 25 restorations were evaluated at 6-month
      intervals during the 30-month period using a modified US Public Health Service
      (USPHS) criteria by two independent evaluators precalibrated at 85% reliability.
      No failures were reported and alpha scores were recorded for all parameters.
      Statistical analysis was performed using a Chi-square test (chi(2)) and the
      Fisher's exact test. Sixteen of the 25 samples (64%) exhibited preoperative
      sensitivity to air (chi(2)=10.6; p=0.001). A significant difference in tooth
      sensitivity was reported after completion of the restorations. No teeth exhibited
      sensitivity both at the 2-week recall and the 30-month follow-up (chi(2)=23.5; p
      < 0.0001). CONCLUSION: Microhybrid composite resin demonstrated excellent
      clinical performance in direct cuspal coverage at completion of a 30-month
      evaluation. CLINICAL SIGNIFICANCE In selected clinical situations, cuspal
      coverage direct posterior composite restorations may represent a valid
      alternative to conventional indirect restorations.

PMID- 16987322
TI  - The sterility of dental burs directly from the manufacturer.
AB  - BACKGROUND: The purpose of this research was to assess the sterility of burs
      directly from manufacturers. The authors wished to determine the types of
      bacteria, if any, found on nonsterilized burs. METHODS: The authors used burs
      from a major manufacturer. Sterilized and nonsterilized burs were cultured for
      bacteria. Any burs found to be contaminated were further cultured on agar plates.
      The bacteria on the plates were identified by a commercial laboratory. RESULTS:
      Of the 100 sterilized and nonsterilized burs, the authors found none of the
      sterilized burs to be contaminated. Eight of the nonsterilized burs showed growth
      of bacteria after 24 hours. Seven of the eight bacteria identified on the burs
      belonged to the genus Bacillus. CONCLUSIONS: The Bacillus genus is encountered in
      daily living and is not considered to be pathogenic; however, there have been
      documented cases of infection in humans in which these bacteria dominate. They
      should never be introduced into the bloodstream. CLINICAL SIGNIFICANCE The
      dentist must consider that soft tissue exposure may be unavoidable with
      subgingival restorations or even those close to the gingiva. Therefore, it is
      imperative that the dentist use sterile burs during dental procedures. This
      article will prove the necessity for sterile burs and leave the rest to the
      manufacturers.

PMID- 16987324
TI  - Effect of 10% carbamide peroxide dental bleaching on microhardness of filled and
      unfilled sealant materials.
AB  - PURPOSE: The purpose of this study was to quantitatively evaluate the effect of
      10% carbamide peroxide on the microhardness of pit and fissure sealant materials.
      METHODS: Fluroshield, Vitroseal Alfa, and one unfilled (Clinpro) sealants were
      placed in Teflon matrices (4 mm in diameter by 2 mm in height) and polymerized
      for 40 seconds. A total of 20 specimens were prepared for each material, in which
      half were assigned as the control group (stored in artificial saliva and no
      bleaching treatment). For the remaining half, Clarigel Gold bleaching agent (10%
      carbamide peroxide) was placed over the specimen surface for 4 hours/day during 4
      weeks. When specimens were not under bleaching treatment, they were kept in
      artificial saliva. Afterwards, specimens were subjected to Knoop microhardness
      testing using a 25-g load for 5 seconds. Five measurements were made on the
      sealants' surfaces and then calculated in Knoop hardness values. The data were
      statistically analyzed by two-way analysis of variance and Tukey's tests with a
      5% confidence level. RESULTS: The results of this in vitro study showed that the
      application of a carbamide peroxide-based bleaching material significantly
      affected the microhardness values of filled sealant materials. The bleaching
      agent did not affect the microhardness of the unfilled sealant. CLINICAL
      SIGNIFICANCE The results of this in vitro study suggest that the bleaching agents
      altered the surface hardness of filled sealant restorative materials. This could
      possibly lead to increased wear and surface roughness.

PMID- 16987326
TI  - Endodontic update 2006.
AB  - The past 10 years have witnessed more significant changes in the art and science
      of endodontics than the previous 100 years. This observation is no surprise,
      given that change is our only constant. The rate of change, however, has been
      anything but constant. The rate has accelerated so fast that all clinicians in
      the field of dentistry need a reliable source to guide us in what works. What
      works today in endodontics is the theme of this update. The discoveries and
      advancements in endodontic technology, instruments, and materials enable
      practitioners to achieve treatment outcomes that were previously considered
      unattainable. For example, in nonsurgical endodontic treatment, nickel titanium
      technology consistently can produce predictable radicular preparations that can
      be easily obturated. In nonsurgical re-treatment, the previous endodontic
      obturation attempt frequently can be removed and successfully re-treated largely
      because of enhanced vision and coaxial lighting from the operating microscope.
      Importantly, careful nonsurgical re-treatment usually can be accomplished without
      disruption to the existing restorations and without risk to ferrule integrity. In
      endodontic surgery underfilled foramina, and the isthmi between them, predictably
      can be connected and obturated with state-of-the-art miniature instruments.
      CLINICAL SIGNIFICANCE This article reviews the clinical endodontic breakthroughs
      encountered during the last decade and focuses on three primary topics: (1)
      finding canals; (2) following canals; and (3) finishing canals. Every day,
      dentists are faced with the interdisciplinary treatment planning question of to
      "save or not to save a tooth?" Dentists must routinely make the decision of
      whether to remove or restore the tooth based on biology, structure, function,
      esthetics, and value.(1) Occasionally, the endodontically treated tooth can be
      the weakest link in the restorative and esthetic sequence. This article examines
      the current state of endodontic technology, as well as the fundamentals of
      endodontic mechanics needed to achieve the most predictable endodontic outcome
      with the highest degree of success.

PMID- 16987327
TI  - At-home bleaching: pulpal effects and tooth sensitivity issues, part II.
AB  - The most common side effect of at-home bleaching is transient tooth sensitivity.
      Despite its high frequency, this phenomenon is not well understood. This is the
      second of a two-part Critical Appraisal on tooth sensitivity associated with at
      home bleaching. The first installment reviewed articles that focus on the
      incidence of sensitivity, long-term effects of bleaching, and related pulpal
      concerns. This installment also covers pulpal concerns, as well as the prevention
      of sensitivity during at-home whitening treatments.

PMID- 16987328
TI  - Xerostomia (dry mouth).

PMID- 16987329
TI  - The developmental cycle of Ehrlichia chaffeensis in vertebrate cells.
AB  - Ehrlichia chaffeensis, an obligatory intracellular bacterium, has two forms in
      mammalian cells: small dense-cored cells (DC) with dense nucleoid and larger
      reticulate cells (RC) with uniformly dispersed nucleoid. We have determined by
      electron microscopy that DC but not RC attaches to and enters into the host cells
      and RC but not DC multiples inside the host cells. Analysis of outer membrane
      protein expression by confocal microscopy showed that RC expressed the 28 kDa
      outer membrane protein (p28), the intermediate form, which were transforming from
      RC to DC, expressed both gp120 and p28, and the mature DC expressed gp120 only.
      The TCID50 of DC is 6 log10 higher than RC. We conclude that E. chaffeensis has a
      developmental cycle, in which the DC attaches to and enters into the host cells,
      and transforms into RC and the RC multiplies by binary fission for 48 h and then
      matures into DC at 72 h.

PMID- 16987330
TI  - The differential expression of Yersinia pseudotuberculosis adhesins determines
      the requirement for FAK and/or Pyk2 during bacterial phagocytosis by macrophages.
AB  - Phagocytosis of Yersinia pseudotuberculosis by macrophages is initiated by
      interactions between host cell integrin receptors and the bacterial adhesins,
      invasin and YadA. Two non-receptor protein tyrosine kinases, FAK and Pyk2, have
      been implicated in this process. In this study, we investigated the mechanisms of
      activation and functional requirements for these kinases during phagocytosis. A
      panel of Yersinia strains that differentially express invasin and YadA were used
      to infect cells in which FAK and/or Pyk2 expression was reduced by RNA
      interference. Bacterial strains that simultaneously express invasin and YadA
      activated FAK and Pyk2 signalling pathways that perform non-redundant functions
      required for Yersinia internalization. In contrast, FAK activation was found to
      be sufficient for phagocytosis of bacteria expressing invasin alone, and Pyk2
      activation was sufficient when YadA was expressed in the absence of invasin.
      Based on these data, we suggest that the activation states of FAK and Pyk2, as
      well as the subsequent signalling events that lead to phagocytosis, are
      differentially regulated through the unique mechanisms of integrin engagement
      utilized by invasin and YadA. These findings lend insight into the molecular
      events that control bacterial phagocytosis as well as other integrin-based
      processes such as cell adhesion and migration.

PMID- 16987331
TI  - The bacterial gene lfpA influences the potent induction of calcitonin receptor
      and osteoclast-related genes in Burkholderia pseudomallei-induced TRAP-positive
      multinucleated giant cells.
AB  - Burkholderia pseudomallei is a facultative intracellular pathogen and the
      causative agent of melioidosis, a spectrum of potentially fatal diseases endemic
      in Northern Australia and South-East Asia. We demonstrate that B. pseudomallei
      rapidly modifies infected macrophage-like cells in a manner analagous to
      osteoclastogenesis. These alterations include multinucleation and the expression
      by infected cells of mRNA for factors required for osteoclastogenesis: the
      chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory
      protein 1 gamma (MIP-1gamma), 'regulated on activation normal T cell expressed
      and secreted' (RANTES) and the transcription factor 'nuclear factor of activated
      T-cells cytoplasmic 1' (NFATc1). An increase in expression of these factors was
      also observed after infection with Burkholderia thailandensis. Expression of
      genes for the osteoclast markers calcitonin receptor (CTR), cathepsin K (CTSK)
      and tartrate-resistant acid phosphatase (TRAP) was also increased by B.
      pseudomallei-infected, but not by B. thailandensis-infected cells. The expression
      by B. pseudomallei-infected cells of these chemokine and osteoclast marker genes
      was remarkably similar to cells treated with RANKL, a stimulator of
      osteoclastogenesis. Analysis of dentine resorption by B. pseudomallei-induced
      osteoclast-like cells revealed that demineralization may occur but that authentic
      excavation does not take place under the tested conditions. Furthermore, we
      identified and characterized lfpA (for lactonase family protein A) in B.
      pseudomallei, which shares significant sequence similarity with the eukaryotic
      protein 'regucalcin', also known as 'senescence marker protein-30' (SMP-30). LfpA
      orthologues are widespread in prokaryotes and are well conserved, but are
      phylogenetically distinct from eukaryotic regucalcin orthologues. We demonstrate
      that lfpA mRNA expression is dramatically increased in association with
      macrophage-like cells. Mutation of lfpA significantly reduced expression of the
      tested host genes, relative to the response to wild-type B. pseudomallei. We also
      show that lfpA is required for optimal virulence in vivo.

PMID- 16987332
TI  - Uncoupling of oxidative phosphorylation enables Candida albicans to resist
      killing by phagocytes and persist in tissue.
AB  - After five serial passages of Candida albicans SC5314 through murine spleens by
      intravenous inoculation, we recovered a respiratory mutant (strain P5) that
      exhibited reduced colony size, stunted growth in glucose-deficient media,
      increased oxygen consumption and defective carbohydrate assimilation. Strain P5
      was indistinguishable from SC5314 by DNA typing methods, but had a greater
      concentration of mitochondria by SYTO18 staining. Treatment with various
      inhibitors demonstrated that strain P5's electron transport chain was intact and
      oxidative phosphorylation was uncoupled. During disseminated candidiasis, the
      mutant did not kill mice or cause extensive damage to kidneys. The burden of
      strain P5 within kidneys on the first 3 days of disseminated candidiasis was
      significantly reduced. By days 28 and 60, it was similar to that at the time of
      death among mice infected with SC5314, suggesting that the mutant persisted and
      proliferated without killing mice. Strain P5 was resistant to phagocytosis by
      neutrophils and macrophages. It was also significantly more resistant to
      paraquat, suggesting that it is able to neutralize reactive oxygen species. Our
      findings indicate that regulation of respiration influences the interaction
      between C. albicans and the host. Uncoupling of oxidative phosphorylation might
      be a mechanism by which the organism adapts to stressful host environments.

PMID- 16987333
TI  - Pulse contour analysis: should good-looking curves be trusted?

PMID- 16987334
TI  - Cardiac output--pulse contour analysis vs. pulmonary artery thermodilution.
AB  - BACKGROUND: The aims of this study were to determine the agreement between
      pulmonary artery thermodilution (PA-TD), transpulmonary thermodilution (TP-TD)
      and the pulse contour method, and to test the ability of the pulse contour method
      to track changes in cardiac output. METHODS: Cardiac output was determined twice
      before cardiac surgery with both PA-TD and TP-TD. The precision (two standard
      deviations of the difference between repeated measurements) and agreement of the
      two methods were calculated. Post-operatively, cardiac output was determined with
      the PA-TD and pulse contour methods, and the bias and limits of agreement were
      again calculated. Finally, in patients with heart rates below 60 beats/min or a
      cardiac index of less than 2.5 l/min/m2, atrial pacing was started and the
      haemodynamic consequences were monitored with the PA-TD and pulse contour
      methods. RESULTS: Twenty-five patients were included. The precisions of PA-TD and
      TP-TD were 0.41 l/min [95% confidence interval (CI), +/- 0.07] and 0.48 l/min
      (95% CI, +/- 0.08), respectively. The bias and limits of agreement between PA-TD
      and TP-TD were - 0.46 l/min (95% CI, +/- 0.11) and +/- 1.10 l/min (95% CI, +/-
      0.19), respectively. Post-operatively, the bias and limits of agreement between
      the PA-TD and pulse contour methods were 0.07 l/min and +/- 2.20 l/min,
      respectively. The changes in cardiac output with atrial pacing were in the same
      direction and of the same magnitude in 15 of the 16 patients. CONCLUSION: The
      precision of cardiac output measurements with PA-TD and TP-TD was very similar.
      The transpulmonary method, however, overestimated the cardiac output by 0.46
      l/min. Post-operatively, cardiac output measurements with the PA-TD and pulse
      contour methods did not agree, but the pulse contour method reliably tracked
      pacing-induced changes in cardiac output.

PMID- 16987335
TI  - Agreement between PiCCO pulse-contour analysis, pulmonal artery thermodilution
      and transthoracic thermodilution during off-pump coronary artery by-pass surgery.
AB  - BACKGROUND: Haemodynamic instability during off-pump coronary artery bypass
      surgery (OPCAB) may appear rapidly, and continuous monitoring of the cardiac
      index (CI) during the procedure is advisable. With the PiCCO monitor, CI can be
      measured continuously and almost real time with pulse-contour analysis and
      intermittently with transthoracic thermodilution. The agreement between pulmonal
      artery thermodilution CI (Tpa), transthoracic thermodilution CI (Tpc) and pulse
      contour CI (PCCI) during OPCAB surgery has not been evaluated sufficiently.
      METHODS: In 30 patients scheduled for OPCAB surgery, a pulmonary artery catheter
      and a PiCCO catheter were inserted. At different time points during surgery, Tpa,
      Tpc and PCCI were compared. Measurements were performed after induction of
      anesthesia (T1), after pericardiothomy (T2), after grafting on the anterior (T3),
      posterior (T4) and lateral (T5) walls and after chest closure (T6). The PCCI was
      recalibrated at time point T2-T6. RESULTS: Mean difference and the limits of
      agreements (percentage error) between Tpa and Tpc were: -0.14 +/- 0.60 (22.0%)
      l/min/m2, between Tpa and PCCI: -0.07 +/- 0.92 (33.5%) l/min/m2 and between Tpc
      and PCCI: 0.10 +/- 1.00 (35.5%) l/min/m2. For changes in CI from one time point
      to the next (DeltaCI), the limits of agreements between DeltaCI Tpa and DeltaCI
      Tpc were 0.04 +/- 0.90 l/min/m2, between DeltaCI Tpa and DeltaCI PCCI: -0.02 +/-
      1.22 l/min/m2 and between DeltaCI Tpc and DeltaCI PCCI: -0.08 +/- 1.32 l/min/m2.
      CONCLUSION: In OPCAB surgery, limits of agreement comparing thermodilution
      methods were smaller than comparing PCCI with thermodilution. Recalibration of
      PCCI is therefore advisable.

PMID- 16987336
TI  - A single-model solution for volume kinetic analysis of isotonic fluid infusions.
AB  - BACKGROUND: Volume kinetics was developed to analyze the distribution and
      elimination of intravenously given fluid. However, when groups of patients are
      being compared, the current approach is limited by the need for several models,
      which yield parameters that cannot be compared. To meet the requirement to handle
      all patients in a group individually and without pooling, a new all-encompassing
      model was designed. The aim of this paper was to test whether the new model could
      be used to analyze all patients in a group. METHODS: The new model consists of
      'rate' and 'amount' parameters instead of 'clearance' and 'dilution' parameters.
      With this change, a redundant parameter can be taken out, but the biexponential
      nature is retained. The new parameters are the volume of distribution V1 (ml),
      the intercompartmental rate constant kt/min and the elimination rate constant
      kr/min. The success rates of the new and original models in producing results
      within a set of pre-determined quality requirements were compared using blood
      dilution data from 10 volunteers challenged with intravenous lactated Ringer's
      solution. RESULTS: The new model could be used to analyze all 10 cases within the
      pre-determined criteria, but the original biexponential model failed in 70% of
      cases. The residuals improved with the new model. The medians (interquartile
      ranges) were as follows: V1, 4931 ml (4239-6149 ml); kt), 0.0384/min (0.0024
      0.1140/min); kr, 0.0140/min (0.0015-0.0043/min). CONCLUSION: The new model was
      suited to the analysis of all cases, and is therefore a better approach to study
      how clinical conditions change the distribution and elimination of infused fluid.

PMID- 16987337
TI  - Influence of hydroxyethyl starch 130/0.4 in pulmonary neutrophil recruitment and
      acute lung injury during polymicrobial sepsis in rats.
AB  - BACKGROUND: Acute lung injury (ALI) is a progressive syndrome associated with
      significant mortality in sepsis patients. Neutrophils are key cells in the
      inflammatory response that characterizes ALI. This study was designed to explore
      the effects of hydroxyethyl starch (HES) 130/0.4 (a novel plasma substitute) on
      pulmonary neutrophil recruitment and associated ALI in a rat sepsis model induced
      by cecal ligation and puncture (CLP). METHODS: Animals were randomly assigned to
      six groups [saline control; CLP and saline; CLP and HES (7.5, 15 and 30 ml/kg);
      and HES control], subjected to CLP and infused with or without HES 130/0.4 4 h
      after CLP. Six hours later, the pulmonary capillary permeability (PCP),
      myeloperoxidase (MPO) activity, lung histological changes, tumor necrosis factor
      alpha, interleukin-1beta and cytokine-induced neutrophil chemoattractant levels,
      P-selectin mRNA expression and nuclear factor-kappa B (NF-kappaB) activation were
      measured. RESULTS: Resuscitation with HES 130/0.4 significantly attenuated the
      CLP-induced increase in PCP, MPO activity, cytokine/chemokine levels, mRNA
      expression of P-selectin and NF-kappaB activation, all of which are involved in
      the recruitment of neutrophils. Groups receiving the higher doses of HES 130/0.4
      (15 and 30 ml/kg) were more adequately resuscitated. CONCLUSION: HES 130/0.4 can
      inhibit CLP-induced neutrophil recruitment and subsequent ALI by attenuating
      cytokines/chemokines, adhesion molecule-mediated inflammation and NF-kappaB
      activation.

PMID- 16987338
TI  - Effects of two different hydroxyethyl starch solutions (HES200/0.5 vs.
      HES130/0.4) on the expression of platelet membrane glycoprotein.
AB  - BACKGROUND: There are various hydroxyethyl starch (HES) solutions with different
      degrees of hydroxylation and different molecular weights. HES200/0.5 solution is
      most commonly used. HES130/0.4 is a new HES solution and is the 'state-of-the
      art' in volume substitution. However, the mechanism of the observed
      anticoagulation action of HES has not been fully delineated. The objective of
      this study was to further investigate the effect of HES200/0.5 and HES130/0.4 on
      platelet coagulation. METHODS: Sixty ASA I-II patients undergoing elective minor
      surgery were randomly allocated to receive an intravenous infusion (20 ml/kg) of
      lactated Ringer's solution (group L), HES200/0.5 (group H) or HES130/0.4 (group
      V) after the induction of anesthesia. The expression of CD42b, CD41/61 and CD62p
      in vivo was assessed on non-stimulated platelets and adenosine diphosphate (ADP)
      agonist-activated platelets using flow cytometry. RESULTS: Resting glycoprotein
      expression of the non-stimulated platelets was observed. HES200/0.5 and
      HES130/0.4 reduced the CD42b, CD41/61 and CD62p expression of ADP-agonist
      activated platelets at 15 min after intravenous infusion. At 6 h after
      intravenous infusion, the trend of decreasing expression of activated CD42b,
      CD41/61 and CD62p was maintained in group H. However, CD42b, CD41/61 and CD62p
      expression returned to the pre-operative level in group V. CONCLUSION: This study
      showed that both HES200/0.5 and HES130/0.4 can inhibit platelet coagulation.
      Platelet dysfunction experienced a faster recovery after the infusion of
      HES130/0.4 than after HES200/0.5. Liquid resuscitation with HES130/0.4 may
      decrease the risk of hemorrhage in the operative period.

PMID- 16987339
TI  - Does Pseudomonas aeruginosa colonization influence morbidity and mortality in the
      intensive care unit patient? Experience from an outbreak caused by contaminated
      oral swabs.
AB  - BACKGROUND: Contaminated oral swabs caused a nationwide monoclonal Pseudomonas
      aeruginosa outbreak involving 27 Norwegian hospitals. The aim of the study was to
      study the consequences on mortality and morbidity of the introduction of this P.
      aeruginosa strain to intensive care unit (ICU) patients. METHODS: Forty-four out
      of 96 patients admitted to the general ICU of Akershus University Hospital during
      the outbreak, ventilated for more than 24 h and with at least one microbiological
      sample, were included and followed until death or hospital discharge. All
      isolated P. aeruginosa strains were genotyped. Demographic data, admission
      diagnosis, Simplified Acute Physiology Score II (SAPS II), Sequential Organ
      Failure Assessment (SOFA) score, comorbidities, and antibiotics used in the first
      week were recorded. RESULTS: The outbreak strain was found in 18 patients (41%)
      of whom seven became infected. Median time to the first positive culture was 4
      days. These 18 patients spent a significantly longer time on mechanical
      ventilation (P =0.03) and had a significantly higher hospital mortality, 55.5%
      vs. 19.2% (P =0.03), than non-colonized patients. The number of patients with
      severe underlying disease was significantly higher (P =0.01) and the decline in
      SOFA score was significantly slower in the pseudomonas group (P =0.02).
      Irrespective of colonization status, patients with severe underlying disease had
      a significantly higher mortality (58%) than those without (16%) (P =0.009).
      CONCLUSION: Use of contaminated oral swabs led to a high rate of early airways
      colonization. Patients with severe underlying disease were more likely to become
      colonized, but whether colonization has any influence on hospital mortality
      requires further study.

PMID- 16987340
TI  - Researcher bias and generalization of results in bias and limits of agreement
      analyses: a commentary based on the review of 50 Acta Anaesthesiologica
      Scandinavica papers using the Altman-Bland approach.

PMID- 16987341
TI  - Using system analysis to build a safety culture: improving the reliability of
      epidural analgesia.
AB  - BACKGROUND: A potentially dangerous situation was revealed by an incident report
      describing the use of an inappropriate device to administer post-operative
      epidural analgesia to a patient on a surgical ward. The incident occurred in a
      1200-bed university affiliated tertiary hospital (Geneva University Hospitals,
      HUG) and involved three clinical departments: anaesthesiology, the surgical
      intensive care unit and urology. METHODS: A multidisciplinary system analysis was
      carried out to identify care-delivery problems and contributory factors.
      Corrective actions were devised on the basis of their ability to prevent and
      absorb unsafe situations. RESULTS: The system analysis identified three care
      delivery problems in relation to the management of epidural analgesia. It enabled
      medical and nursing managers to adopt an interdepartmental set of corrective
      actions: a common protocol for post-operative epidural analgesia, leading to the
      exclusive use of patient-controlled epidural analgesia (PCEA) pumps; greater
      availability of the patient-controlled pumps; the dissemination of guidelines;
      permanent proactive training of nurses by the acute-pain team; the clarification
      of medical responsibilities; and a common help-line phone number for all surgical
      departments. DISCUSSION: The analysis provided a convincing exposure of various
      care-delivery problems and their corresponding contributory factors, as well as
      an opportunity to address a systemic issue in a multidisciplinary way. By thus
      facilitating decisions and corrective actions, the analysis was instrumental in
      strengthening our safety culture.

PMID- 16987342
TI  - Outcome after heroin overdose and cardiopulmonary resuscitation.
AB  - BACKGROUND: The survival of heroin overdose patients resuscitated from cardiac
      arrest is reported to be poor. The aim of our study was to investigate the
      outcome and characteristics of survivors after cardiac arrest caused by heroin
      overdose. METHODS: This was a retrospective study in a medium-sized city
      (population, 560,000). Between 1 January 1997 and 31 December 2000, there were 94
      combined cardiac arrests caused by acute drug poisonings. The main outcome
      measure was survival to discharge. RESULTS: Cardiopulmonary resuscitation was
      attempted in 19 heroin overdose patients (group A) and in 53 patients with
      cardiac arrest caused by other poisonings (group B). Three (16%) vs. six (11%)
      patients were discharged alive (group A vs. B, respectively). The survivors in
      group A had an Emergency Medical Service (EMS)-witnessed cardiac arrest or the
      Emergency Dispatching Centre was called before the arrest occurred. There was no
      statistically significant difference between the two groups in terms of survival.
      Survivors in both groups suffered from acute renal failure (two), hypoglycaemia
      (four) and hypothermia (three). CONCLUSION: Survival after cardiac arrest caused
      by heroin overdose is possible if the arrest is EMS witnessed or the Emergency
      Dispatching Centre is called before the cardiac arrest occurs. In comparison with
      cardiac arrests caused by other poisonings, there was no difference in survival.
      The incidence and mechanism of hypoglycaemia should be examined in further
      studies.

PMID- 16987343
TI  - Naloxone and epinephrine are equally effective for cardiopulmonary resuscitation
      in a rat asphyxia model.
AB  - BACKGROUND: It is not known whether naloxone is as efficacious as epinephrine
      during cardiopulmonary resuscitation (CPR). The aim of the study was to compare
      the effects of naloxone and epinephrine on the outcomes of CPR following
      asphyxial cardiac arrest in rats. METHODS: Cardiac arrest was induced with
      asphyxia by clamping the tracheal tubes. Twenty-four Sprague-Dawley rats were
      randomized prospectively into a saline group (treated with normal saline, 1 ml
      intravenously, n = 8), an epinephrine group (treated with epinephrine, 0.04 mg/kg
      intravenously, n = 8) or a naloxone group (treated with naloxone, 1 mg/kg
      intravenously, n = 8) in a blind fashion during resuscitation after asphyxial
      cardiac arrest. After 5 min of untreated cardiac arrest, conventional manual CPR
      was started and each drug was administered at the same time. RESULTS: The rates
      of restoration of spontaneous circulation (ROSC) were one of eight (12.5%), seven
      of eight (87.5%) and seven of eight (87.5%) in the saline, epinephrine and
      naloxone groups, respectively. The rates of ROSC in the epinephrine and naloxone
      groups were equal and significantly greater than that in the saline group (P =
      0.01 and P = 0.01, respectively). CONCLUSION: The administration of naloxone or
      epinephrine alone may increase the resuscitation rate, and both drugs are equally
      effective for CPR in a rat asphyxia model. However, the mechanism by which
      naloxone produces its efficacy during CPR remains unclear and further
      experimentation will be necessary.

PMID- 16987344
TI  - Propofol inhibits phorbol 12, 13-dibutyrate-induced, protein kinase C-mediated
      contraction of rat aortic smooth muscle.
AB  - BACKGROUND: Propofol induces dose-dependent vasodilation and hypotension in the
      clinical situation, and protein kinase C (PKC)-mediated Ca2+ sensitization plays
      an important role in vascular smooth muscle contraction. This study is designed
      to examine the effects of propofol on the active phorbol ester (phorbol 12, 13
      dibutyrate; PDBu)-induced, PKC-mediated contraction of rat aortic smooth muscle.
      METHODS: The PDBu-induced contraction of endothelium-denuded rat aortic rings was
      measured in the presence or absence of PKC inhibitor, bisindolylmaleimide I, or
      propofol, using isometric force transducers. The PDBu-induced PKC phosphorylation
      of endothelium-denuded rat aortic strips was detected in the presence or absence
      of bisindolylmaleimide I or propofol, using Western blotting. RESULTS: PDBu, but
      not the inactive phorbol ester, 4-alpha-phorbol 12-myristate-13-acetate, dose
      dependently induced both a slowly developing sustained contraction and PKC
      phosphorylation of rat aortic smooth muscle, reaching the peak level at the
      concentration of 10(-6) M. The PDBu (10(-6) M)-induced contraction was dose
      dependently inhibited by bisindolylmaleimide I with reductions of 6.8 +/- 1.8% (P
      > 0.05), 39.8 +/- 8.7% (P < 0.01) and 96.7 +/- 1.4% (P < 0.01) in response to
      concentrations of 5 x 10(-7) M, 10(-6)x M and 5 x 10(-6) M, respectively, and by
      propofol with decreases of 5.2 +/- 1. 6% (P > 0.05), 9.4 +/- 1.7% (P < 0.05),
      65.3 +/- 9.2% (P < 0.01) and 96.2 +/- 1.6% (P < 0.01) in response to
      concentrations of 5 x 10(-7) M, 10(-6) M, 5 x 10(-6) M and 10(-5) M,
      respectively. Both bisindolylmaleimide I and propofol also inhibited the PDBu
      induced increase in the density of the phosphorylated PKC bands in a dose
      dependent manner, with decreases of 6.3 +/- 2.8% (P > 0.05), 42.9 +/- 3.2% (P <
      0.01) and 96.6 +/- 3.4% (P < 0.01) in response to 5 x 10(-7) M, 10(-6) M or 5 x
      10(-6) M bisindolylmaleimide I, respectively, and with decreases of 4.2 +/- 2.5%
      (P > 0.05), 13.5 +/- 1.7% (P < 0.05), 69.5 +/- 3.5% (P < 0.01) and 95.3 +/- 4.3%
      (P < 0.01) in response to 5 x 10(-7) M, 10(-6) M, 5 x 10(-6) M and 10(-5) M
      propofol, respectively. CONCLUSION: Propofol dose-dependently inhibits PDBu
      induced, PKC-mediated contraction of rat aortic smooth muscle.

PMID- 16987345
TI  - Comparison of auditory evoked potential parameters for predicting clinically
      anaesthetized state.
AB  - BACKGROUND: Most of the research efforts to monitor the depth of anaesthesia
      using the mid-latency auditory evoked potential (MLAEP) signal in humans are
      based on the detection of the amplitudes and latencies of the signal peaks.
      Attempts have also been made to combine different time-domain and frequency
      domain parameters. A comparison of different parameters is required to identify
      those which best discriminate the awake state from the anaesthetized state.
      METHODS: Although the sensitivity of MLAEP signal peaks is appreciable in awake
      and light anaesthesia states, it is reduced considerably at the moderate
      anaesthesia level, rendering this method unsuitable for predicting the surgical
      stage of anaesthesia. To overcome this problem, a numerically derived quantity-
      the morphology index--was used which does not require location of the peaks of
      the signal, but, at the same time, reflects the changes in both the latency and
      amplitude of the peaks. AEPs were recorded in the hospital for 18 patients during
      various states, i.e. awake, induction, unconscious and after regaining
      consciousness from halothane anaesthesia. The peak latencies, amplitudes,
      morphology index and peak power frequency (PPF) were calculated. RESULTS: The
      sensitivity and specificity of PPF (89% and 95%, respectively) were found to be
      better than those for Pa and Nb peak amplitudes, their latencies and the
      morphology index. In addition, PPF showed minimum inter-patient variation. The
      mean value (standard deviation) of this parameter was 26.9 (0.67) during the
      awake state, decreased to 17.1 (1.2) during the anaesthetized state, and
      increased again to 26.1 (0.93) when the patients regained full consciousness.
      CONCLUSION: PPF is the best of the four studied MLAEP parameters for the clinical
      characterization of the anaesthetized state during surgery.

PMID- 16987346
TI  - Protective effects of volatile agents against acetylcholine-induced
      bronchoconstriction in isolated perfused rat lungs.
AB  - BACKGROUND: Bronchoactive properties of volatile agents against lung constriction
      are well established. The purpose of this study was to investigate the ability of
      halothane (Hal), isoflurane (Iso), sevoflurane (Sev) and desflurane (Des) to
      alter the lung mechanics in the absence of an airway tone and during
      acetylcholine (Ach)-induced bronchoconstriction. METHODS: Low-frequency pulmonary
      impedance data (ZL) were collected from isolated, normo-perfused rat lungs under
      baseline conditions and following the injection of Ach (0.1 mg/kg) into the
      pulmonary artery. Measurements were performed without the administration of any
      anaesthetic agent in the first phase of the experiments and during inhalation
      without any volatile agent (control group, n = 6) or during inhalation of Hal (n
      = 6), Iso (n = 9), Sev (n = 6) or Des (n = 8) at 1 minimum alveolar concentration
      (MAC). The airway resistance (Raw) and parenchymal damping and elastance were
      estimated from the Z(L) data by model fitting. RESULTS: Under baseline
      conditions, the basic value of Raw was significantly decreased by Des (- 31.2 +/-
      3.8%) and Sev (- 18.0 +/- 4.5%) administration, whereas Hal and Iso did not have
      a statistically significant effect on Raw (- 3.3 +/- 5.1% and - 8.6 +/- 2.4%,
      respectively). Moreover, all four inhalation anaesthetics prevented the increase
      in Raw following Ach administration, the findings ranging between - 14.3 +/-
      11.4% for Hal and - 37.5 +/- 10.9% for Sev. CONCLUSIONS: Our results on a
      denervated isolated perfused lung model demonstrate the potential of Des and Sev
      to decrease the basal airway tone, whereas Iso and Hal are ineffective in this
      regard. All of these volatile agents markedly protect against Ach-induced
      bronchoconstriction.

PMID- 16987347
TI  - Fentanyl reduces desflurane-induced airway irritability following thiopental
      administration in children.
AB  - BACKGROUND: Airway irritation is a major drawback of desflurane anesthesia. This
      study was designed to evaluate the effect of intravenous fentanyl given before
      thiopental induction on airway irritation caused by a stepwise increase in
      desflurane in children. METHODS: Eighty children (2-8 years) were enrolled in a
      randomized, double-blind study. Forty received saline and 40 received 2 microg/kg
      of fentanyl intravenously; this was followed by thiopental sodium 5 mg/kg in both
      groups. Patients were assistant-ventilated with desflurane 1%, which was then
      increased by 1% every six breaths up to 10%. During this period, cough,
      secretion, excitation and apnea were graded and the desflurane concentration at
      which airway irritation symptoms first occurred was recorded. The results were
      analyzed using Pearson's chi-squared test. RESULTS: The incidence of typical
      airway irritation events was lower with fentanyl than with saline (cough, 2.5%
      vs. 42.5%; secretion, 27.5% vs. 82.5%; excitation, 10% vs. 82.5%; apnea, 20% vs.
      65%; P < 0.05). The mean expired desflurane concentration at which the first
      airway irritation symptom occurred was greater with fentanyl than with saline
      (7.3% vs. 5.5%, P < 0.05). CONCLUSIONS: Intravenous fentanyl in children reduces
      airway complications caused by desflurane.

PMID- 16987348
TI  - A case of anaphylactic shock possibly caused by intravesical Hexvix.
AB  - BACKGROUND: We report a case of a 69-year-old Caucasian male who experienced a
      severe drop in blood pressure and a skin rash after fluorescence cystoscopy and
      transurethral resection of the prostate. The diagnostic agent used for
      fluorescence cystoscopy and suspected of causing the anaphylaxis was
      hexaminolevulinate hydrochloride (Hexvix). INCIDENT: A profound fall in blood
      pressure associated with atrial fibrillation, the appearance of a rash, vomiting
      and transient loss of consciousness occurred immediately after surgery. The
      hypotension persisted for several hours despite intensive treatment. The reaction
      commenced approximately 5 h after exposure to Hexvix. There was an increase in
      serum tryptase (almost nine-fold) and a positive skin prick test to undiluted
      Hexvix. CONCLUSION: The mechanism of the anaphylaxis is uncertain, but is
      considered likely to be a non-immunoglobulin E-mediated allergic reaction
      possibly caused by Hexvix. This is the first reported case of a severe allergic
      reaction after intravesical instillation of Hexvix.

PMID- 16987349
TI  - Placebo use to compare the analgesic efficacy of parenteral paracetamol and
      diclofenac in post-operative orthopaedic pain.

PMID- 16987350
TI  - Pulse-contour-derived cardiac output is unreliable in septic shock.

PMID- 16987353
TI  - Pre-operative measurement of heart rate variability and incidence of hypotension.

PMID- 16987355
TI  - Naloxone scavenges reactive oxygen species.

PMID- 16987356
TI  - Stable long-term opioid medication per se does not always cause loss of driving
      ability: the doctor and patient must consider additional risk factors for unsafe
      driving.

PMID- 16987357
TI  - Being a young and inexperienced trainee anesthetist: a phenomenological study on
      tough working conditions.
AB  - BACKGROUND: Physicians at the beginning of their specialist education have been
      reported to be especially exposed to stress and difficult working conditions.
      Considerable worry has also been caused by reports about anaesthetists dying at a
      younger age than other specialists as well as by reports about higher than
      average suicide rates among anaesthetists. Maybe as a consequence, many young
      doctors are reluctant to choose anaesthesiology as their future specialty. The
      aim of this study was to investigate what difficulties trainee anaesthetists
      experience at work. METHODS: Nineteen trainee anaesthetists in six Swedish
      hospitals were interviewed. Phenomenological analysis of the interview text was
      performed. RESULTS: All trainees had experienced considerable, sometimes extreme
      demands at work. Most of them often felt insufficient and inadequate and had
      problems with the professional role. Support from consultants was sometimes
      lacking. Some trainees expressed deep feelings of loneliness and helplessness in
      difficult clinical situations. CONCLUSIONS: This study shows that trainee
      anaesthetists have to live up to high work demands, often with very little
      support. Because too much stress is an obstacle to professional learning, such
      working conditions are a hindrance to good specialist education. The first
      measure to be taken should be to ensure that all trainee anaesthetists always
      have easy access to senior cover.

PMID- 16987358
TI  - Allocation of tasks between anesthesiologists and anesthesia nurses in Finland.
AB  - BACKGROUND: The shortage of anesthesiologists in Finland is worsening. A survey
      was carried out in 2003 among head anesthesiologists and head nurses to clarify
      current practice and the potentials for reorganizing tasks between
      anesthesiologists and anesthesia nurses. A national working group analyzed the
      results. METHODS: A questionnaire concerning doctor and nurse resources in
      anesthesiology, current allocation of tasks, and opinions on how these tasks
      could be reallocated was sent to 87 head anesthesiologists and 32 head nurses in
      45 different hospitals. The answers from the doctors and nurses were compared.
      RESULTS: The response rate of doctors and nurses was 87% and 100%, respectively.
      In the enrolled hospitals there were 64 unoccupied positions for specialists in
      anesthesiology. The ratio of anesthesiologists to operation rooms (OR) they
      attended varied between 0.3 and 1.5. Doctors and nurses reported the allocation
      of tasks quite similarly. The great majority of respondents considered spinal,
      epidural, and interscalene brachial plexus blocks, and the induction of general
      anesthesia to be tasks that should be performed by an anesthesiologist. Very few
      respondents of either profession were willing to reallocate tasks so that nurses
      could deliver general anesthesia, including endotracheal intubation, even in low
      risk patients. CONCLUSION: Nurses could be trained nationwide to perform
      procedures already performed by locally trained nurses in some hospitals. To cope
      with the shortage of anesthesiologists, other strategies must be adopted in
      addition to transferring part of their work load to nurses.

PMID- 16987359
TI  - Assessing cognition and psychomotor function under long-term treatment with
      controlled release oxycodone in non-cancer pain patients.
AB  - BACKGROUND: The therapeutic use of opioids can be associated with altered
      cognition and impaired psychomotor function. Several studies have demonstrated
      the impact of opioid therapy on psychomotor performance and cognition, but no
      data exist about the effect of long-term treatment with controlled release
      oxycodone (CRO) on driving ability. METHODS: Thirty patients suffering from
      chronic non-cancer pain who had been treated with stable doses of CRO where
      included in a prospective trial and compared with 90 healthy volunteers (matched
      pairs). A computerized test battery that was developed to assess the driving
      ability of traffic delinquents in Germany was employed. Attention reaction,
      visual orientation, motor coordination and vigilance were evaluated. The data
      from a total of 11 parameters were assessed and for each test a relevant score
      was defined. As the primary endpoint the sum score of the three relevant scores
      was determined. A weaker statistical means to assess the patients' performance is
      to compare the test results with an age-independent control group. Individuals
      performing worse than the 16th percentile of this control group are considered to
      be unable to drive according to German legislation. RESULTS: Significant non
      inferiority could not be demonstrated for the primary endpoint. However, driving
      ability as defined as a result above the 16th percentile did not differ
      significantly between the patients receiving CRO and the age-independent control
      group. CONCLUSION: The use of CRO does not prohibit driving, but individual
      assessment is necessary.

PMID- 16987360
TI  - Plasma concentrations following repeated rectal or intravenous administration of
      paracetamol after heart surgery.
AB  - BACKGROUND: Paracetamol is commonly used for post-operative pain management in
      combination with more potent analgesics. The best route of paracetamol
      administration after major surgery, when oral intake may not be optimal, is not
      known. Our primary purpose was to study plasma concentrations after the 1st and
      4th dose of 1 g of paracetamol given either rectally or intravenously (i.v.)
      after major surgery. METHODS: In this prospective, randomized study, 48 patients
      undergoing heart surgery were randomized upon arrival to the intensive care unit
      (ICU) to receive paracetamol every 6th hour either as suppositories or
      intravenous injections. In half the patients (n = 24), blood samples for
      paracetamol concentration were obtained before and 20, 40 and 80 min after the
      first dose. In the other patients (n = 24), additional samples were taken prior
      to, and at 20, 40, 80 min and 4 and 6 h after, the 4th dose. RESULTS: Plasma
      paracetamol concentration peaked (95 +/- 36 micromol/l) within 40 min after
      initial i.v. administration but did not increase within 80 min after the 1st
      suppository. Plasma concentration before the 4th dose was 74 +/- 51 and 50 +/- 27
      in the rectal and i.v. groups, respectively. Paracetamol concentration peaked 20
      min after the 4th dose for the i.v. patients (210 +/- 84 micromol/l) and declined
      to 99 +/- 27 micromol/l at 80 min as compared with the rectal patients 69 +/- 44
      to 77 +/- 48 micromol/l. CONCLUSION: Both time course and peak plasma
      concentrations of paracetamol given rectally differ from the one seen after
      intravenous administration. The clinical impact of these differences needs
      further investigation.

PMID- 16987362
TI  - Coloured chlorhexidine cotton pads may help to identify cerebrospinal fluid
      during epidural or spinal anaesthesia.
AB  - BACKGROUND: During complicated technical conditions in epidural or spinal
      anaesthesia, it may be difficult to safely identify the epidural space. The
      confirmation or exclusion of the presence of cerebrospinal fluid (CSF) during the
      procedure of regional anaesthesia is helpful to determine the position of the
      epidural needle in order to proceed with the anaesthetic block. METHODS: We have
      examined how CSF and different anaesthetic solutions change the colour of
      yellowish phenol red absorbed in cotton pads. RESULTS: Sodium chloride and local
      anaesthetic agents do not change the colour of yellowish phenol red. However, CSF
      immediately changes the colour from yellow to pink or red. Letting a drop of
      fluid from the epidural/spinal needle fall on to the cleaning pads filled with
      phenol red will enable the anaesthesiologist to immediately confirm the presence
      or absence of CSF. The higher pH of CSF relative to that of sodium chloride and
      local anaesthetic agents explains the different colour reaction. CONCLUSION: This
      colour reaction quickly identifies the presence of CSF and thus the intradural
      space during the procedure of spinal or epidural anaesthesia.

PMID- 16987361
TI  - Ultrasound guidance improves the success rate of a perivascular axillary plexus
      block.
AB  - BACKGROUND: Traditional approaches to performing brachial plexus blocks via the
      axillary approach have varying success rates. The main objective of this study
      was to evaluate if a specific technique of ultrasound guidance could improve the
      success of axillary blocks in comparison to a two injection transarterial
      technique. METHODS: Fifty-six ASA physical status I-III patients presenting for
      elective hand surgery were prospectively randomized to receive an axillary block
      performed by either a transarterial technique (Group TA) or an ultrasound-guided
      perivascular approach (Group US). Both groups received a total of 30 ml of 1.5%
      lidocaine (225 mg) with 5 microg/ml epinephrine. Patients were then evaluated for
      block onset in specific nerve distributions and whether or not the block acted as
      a surgical anesthetic. RESULTS: Group TA sustained more failures defined as
      conversion to general anesthesia or the inability to localize the artery [Group
      TA eight patients (29%) vs. Group US in which 0 patients required conversion to
      general anesthesia (0%) P < 0.01]. Group US demonstrated a reduction in
      performance times vs. Group TA (7.9 +/- 3.9 min vs. 11.1 +/- 5.7 min, P < 0.05).
      By 30 min post-injection, there were no significant differences between groups TA
      and US in terms of the proportion of patients demonstrating a complete motor or
      sensory loss. CONCLUSION: Ultrasonographic guidance improves the overall success
      rate of axillary blocks in comparison to a transarterial technique.

PMID- 16987363
TI  - Etoricoxib pre-medication for post-operative pain after laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Etoricoxib alleviates and prevents acute pain. The hypothesis of our
      study was that the pre-operative use of etoricoxib would reduce the post
      operative need for additional pain treatment. METHODS: In this double-blind,
      randomized and active placebo-controlled study, 75 patients were pre-medicated
      1.5 h before elective laparoscopic cholecystectomy with 120 mg of etoricoxib
      (E120 group), the same dose of etoricoxib combined with 1 g of paracetamol (E + P
      group) or placebo (Pla group). To alleviate post-operative pain, a patient
      controlled analgesia (PCA) device was programmed to deliver 50 microg of fentanyl
      intravenously (lockout time, 5 min). The pain intensity and nausea were assessed
      using a visual analogue scale (VAS). The number of patients with post-operative
      nausea and vomiting was recorded. Blood loss was compared between the groups.
      Because the operations are almost blood-less, the operation time was also
      recorded to compare the possible effect on bleeding time. RESULTS: Pre-medication
      with etoricoxib or etoricoxib plus paracetamol had a statistically significant
      fentanyl-sparing effect 2-20 h post-operatively compared with placebo (P =
      0.001). No significant differences were demonstrated in fentanyl-sparing effect
      between the E120 and E + P groups. No significant differences in pain intensity
      were found between the three study groups. No significant differences were
      observed between the groups with regard to nausea, blood loss, duration of
      anaesthesia or duration of surgery. CONCLUSION: Etoricoxib is suitable for pre
      medication before laparoscopic cholecystectomy as it reduces the need for post
      operative opioids. Opioid-related side-effects, however, were not reduced in the
      present study, despite the observed opioid-sparing effect of etoricoxib and
      combined etoricoxib and paracetamol.

PMID- 16987364
TI  - Continuous peripheral nerve block catheter tip adhesion in a rat model.
AB  - BACKGROUND: Continuous peripheral nerve block (CPNB) has been used effectively in
      combat casualties from Iraq and Afghanistan to provide surgical anesthesia and
      extended duration analgesia during evacuation and convalescence. Little
      information is available concerning catheter tip tissue reaction with prolonged
      use. METHODS: Forty-eight male Sprague-Dawley rats were assigned (12 per group)
      to one of four catheter tip designs provided by Arrow International: group A, 20
      gauge catheter with three side-holes and a bullet-shaped tip; group B, 19-gauge
      StimuCath catheter with coiled omni-port end with hemispherical distal tip; group
      C, 19-gauge catheter with single end-hole in conducting tip; group D, 19-gauge
      catheter with closed conducting tip with four side-holes. Following laparotomy, a
      randomly assigned catheter tip was sutured to the parietal peritoneal wall with
      the tip extending between experimental injuries created on the abdominal wall and
      cecum. After 7 days in situ, the catheter tips were removed from the adhesion
      mass using a force gauge, and the grams of force needed for removal were
      recorded. RESULTS: The mean force +/- standard deviation values were 1.09 +/-
      1.21 g for group A, 21.20 +/- 30.15 g for group B, 0.88 +/- 1.47 g for group C
      and 1.60 +/- 2.50 g for group D. The variation of each catheter group mean force
      compared with that of group B was significant (P < 0.05). There was no
      significant difference in adhesion force between groups A, C and D. CONCLUSIONS:
      These results suggest that the manufactured design of a CPNB catheter tip can
      contribute to the adhesion of the tip in an intense inflammatory environment.
      This finding may have important clinical implications for CPNB catheters left in
      place for extended periods of time.

PMID- 16987365
TI  - Excess mortality in winter in Finnish intensive care.
AB  - BACKGROUND: In the general population, mortality from acute myocardial
      infarctions, strokes and respiratory causes is increased in winter. The winter
      climate in Finland is harsh. The aim of this study was to find out whether there
      are seasonal variations in mortality rates in Finnish intensive care units
      (ICUs). METHODS: We analysed data on 31,040 patients treated in 18 Finnish ICUs.
      We measured severity of illness with acute physiology and chronic health
      evaluation II (APACHE II) scores and intensity of care with therapeutic
      intervention scoring system (TISS) scores. We assessed mortality rates in
      different months and seasons and used logistic regression analysis to test the
      independent effect of various seasons on hospital mortality. We defined 'winter'
      as the period from December to February, inclusive. RESULTS: The crude hospital
      mortality rate was 17.9% in winter and 16.4% in non-winter, P = 0.003. Even after
      adjustment for case mix, winter season was an independent risk factor for
      increased hospital mortality (adjusted odds ratio 1.13, 95% confidence interval
      1.04-1.22, P = 0.005). In particular, the risk of respiratory failure was
      increased in winter. Crude hospital mortality was increased during the main
      holiday season in July. However, the severity of illness-adjusted risk of death
      was not higher in July than in other months. An increase in the mean daily TISS
      score was an independent predictor of increased hospital mortality. CONCLUSION:
      Severity of illness-adjusted hospital mortality for Finnish ICU patients is
      higher in winter than in other seasons.

PMID- 16987366
TI  - Efficacy of multimodal optimization of mobilization and nutrition in patients
      undergoing hip replacement: a randomized clinical trial.
AB  - BACKGROUND: The aim of this trial was to assess the effects of optimization of
      mobilization and nutrition on patients undergoing primary total hip replacement
      (THR). METHODS: Seventy-nine patients undergoing elective primary THR were
      recruited prospectively. After randomization, one group received optimized pre
      operative information and enforced mobilization and nutrition, another group
      received conventional peri-operative care. Epidural anaesthesia and post
      operative epidural analgesia with local anaesthetics and opioids were used in all
      cases. Outcome related to length of stay, complications, pain, mobilization,
      energy intake, and physical activities of daily living (PADL). RESULTS: Although
      mobilization and nutrition were highly significantly increased in the
      intervention group, the reduction in length of stay was moderate (7.0 vs. 8.0
      days P = 0.019). We found no differences between groups in relation to
      complications or pain. In the intervention group, the median day of independence
      in PADL was the third post-operative day (2 : 6 day) and the fourth post
      operative day (2 : 7 day) in the control group. The difference was not
      significant. CONCLUSION: Compared with conventional care, optimal and aggressive
      nutrition and mobilization resulted in a very moderate reduction in length of
      stay. There were no differences regarding pain, complications or time until
      independence in PADL.

PMID- 16987367
TI  - Oscillometric brachial mean artery pressures are higher than intra-radial mean
      artery pressures in intensive care unit patients receiving norepinephrine.
AB  - BACKGROUND: Norepinephrine is frequently used in intensive care unit (ICU)
      patients to raise and maintain an adequate mean arterial pressure (MAP). Conflict
      arises as to which MAP should guide vasopressor dose, as oscillometric MAP in the
      brachial artery often diverges from intra-radial MAP. We wanted to estimate the
      magnitude of this difference in ICU patients receiving norepinephrine, and to see
      whether the patient age, norepinephrine dose, age of radial catheter, ventilation
      treatment or severity of illness influenced the difference. METHODS: Prospective
      observational study comparing oscillometric MAP and intra-radial MAP performed in
      a central hospital-based surgical ICU during the period from February 2002
      through to October 2003. Sixty-eight consecutive patients who received a
      norepinephrine infusion to maintain MAP above 70 mmHg were included. The mean
      arterial blood pressure was measured both oscillometrically and in the
      ipsilateral radial artery. RESULTS: Oscillometric MAP was on average 6.6 mmHg
      higher (95% CI 5.3-7.9) than intra-radial MAP in the 134 sets of measurements (P
      < 0.001). The patient's age (P = 0.319), norepinephrine dosage (P = 0.959) the
      age of the radial catheter (P = 0.992) were not significant. The difference in
      MAP was marginally greater in ventilated patients (P = 0.061) and significantly
      greater as the simplified acute physiology score (SAPS) score increased (P =
      0.022). CONCLUSIONS: MAP measured oscillometrically over the brachial artery
      directly in the radial artery gave different results in an ICU population
      receiving norepinephrine. In more than one of four patients this difference is so
      large, and increases with illness severity, that the selection of any one method
      would influence treatment.

PMID- 16987368
TI  - Acupuncture stimulation of ST-36 (Zusanli) significantly mitigates acute lung
      injury in lipopolysaccharide-stimulated rats.
AB  - BACKGROUND: We sought to investigate the potential therapeutic effects of
      acupuncture stimulation of ST-36 (Zusanli) on endotoxemia-induced acute lung
      injury in lipopolysaccharide (LPS)-stimulated rats. METHODS: Sixty rats were
      randomized into six groups (n = 10): (i) lipopolysaccharide (LPS) control group,
      (ii) normal saline (N/S) control group, (iii) LPS plus ST-36 group, (iv) N/S plus
      ST-36 group, (v) LPS plus sham point (Sham) group, and (vi) N/S plus Sham group.
      Manual acupuncture stimulation of ST-36 (designated as 'ST-36') or a 'non
      acupoint' (designated as 'Sham') was performed in lightly immobilized rats for 30
      min. Then, LPS injection was employed to induce sepsis. Rats were killed at 6 h
      after LPS injection and lung injury, nitric oxide (NO) biosynthesis and inducible
      NO synthase (iNOS) expression were assayed. RESULTS: Significant lung injury,
      pulmonary iNOS expression and systemic and pulmonary NO biosynthesis were noted
      in the LPS groups. Rats in the LPS plus Sham group had lung injury, pulmonary
      iNOS expression, systemic and pulmonary NO biosynthesis similar to those observed
      in the LPS group. However, the degree of lung injury, pulmonary iNOS expression
      and pulmonary NO biosynthesis, but not systemic NO biosynthesis, were
      significantly attenuated in the LPS plus ST-36 group as compared with those in
      both the LPS group and the LPS plus Sham group. CONCLUSION: Acupuncture
      stimulation of ST-36 may be effective as a prophylaxis measure against sepsis.
      However, results from this study do not support the use of acupuncture for the
      treatment of sepsis.

PMID- 16987369
TI  - Comparison of radiographic landmarks and the echocardiographic SVC/RA junction in
      the positioning of long-term central venous catheters.
AB  - BACKGROUND: When implanting a permanent central venous catheter, the usual aim is
      to place the tip at the superior vena cava/right atrial (SVC/RA) junction.
      However, data validating radiographic landmarks of the SVC/RA junction are
      limited. This investigation was undertaken to compare the radiographic landmarks
      with the SVC/RA junction as determined by transesophageal echocardiography (TEE).
      METHODS: In 20 adult oncologic patients undergoing implantation of a permanent
      subcutaneous central venous catheter, the catheter tip was placed in the SVC/RA
      junction under TEE guidance. The position of the catheter tip on chest X-ray,
      which represented the echocardiographic SVC/RA junction, was then compared with a
      standard radiographic landmark of the SVC/RA junction and with thoracic vertebral
      levels. RESULTS: In all but two patients radiographic SVC/RA junctions were
      identified. The echocardiographic SVC/RA junction ranged from 0.6 cm above to 2.8
      cm below the radiographic SVC/RA junction. There was a significant difference
      between the distance from the carina to the radiographic SVC/RA junction and the
      distance from the carina to the echocardiographic SVC/RA junction. The thoracic
      vertebral body correlating with the echocardiographic SVC/RA junction ranged from
      the sixth to the ninth level. CONCLUSION: Both the radiographic SVC/RA junction
      and the thoracic vertebral bodies are not reliable landmarks for the SVC/RA
      junction defined by TEE. Physicians should be aware that using the radiographic
      SVC/RA junction to confirm proper positioning of permanent central venous
      catheters risks placing the catheter tip in the upper SVC, with subsequent
      potential long-term complications. More reliable radiographic landmarks for the
      SVC/RA junction should be investigated.

PMID- 16987370
TI  - Can remifentanil be a better choice than propofol for colonoscopy during
      monitored anesthesia care?
AB  - BACKGROUND AND OBJECTIVE: This prospective, randomized trial was designed to test
      the hypothesis that continuous infusion of low-dose remifentanil can provide
      effective analgesia, sedation, amnesia, patient comfort and stable recovery
      profile without respiratory depression when compared with propofol infusion
      during colonoscopy. METHODS: One hundred patients were randomly assigned to
      receive either remifentanil (group R, 0.5 microg/kg followed by 0.05
      microg/kg/min, n = 50) or propofol (group P, 0.5 mg/kg followed by 50
      microg/kg/min, n = 50). Supplemental doses of remifentanil 12.5 microg in group R
      and propofol 10 mg in group P were given to treat complaints of moderate to
      severe pain and discomfort. Hemodynamic and respiratory data, pain, discomfort
      and sedation scores, patient and gastroenterologist satisfaction and recovery
      profiles were recorded. RESULTS: The duration of colonoscopy was longer in group
      P. The mean arterial pressure, heart rate and end-tidal CO2 remained stable
      during the procedure and were comparable between the groups. After bolus
      injection of the study drugs, the respiratory rate and oxygen saturation values
      were lower in group R than in group P. Only one patient in group R required
      airway support. Pain and discomfort scores were better in group R than in group
      P. Sedation levels were higher in group P than in group R. Group P needed more
      supplemental doses than group R. The time to reach an Aldrete score of nine or
      more was shorter in group R, but discharge times were similar in the two groups.
      Amnesia was better in group P. Nausea and vomiting were more frequent in group R
      during the recovery phase. CONCLUSION: Low-dose remifentanil infusion with
      intermittent bolus injections can provide adequate sedation, amnesia and better
      analgesia than propofol infusion during colonoscopy. However, remifentanil
      induced nausea and vomiting may be a problem during the recovery phase.

PMID- 16987371
TI  - GABAmimetic intravenous anaesthetics inhibit spontaneous Ca2+ -oscillations in
      cultured hippocampal neurons.
AB  - BACKGROUND: Spontaneous Ca2+ -oscillations are a possible mechanism of Ca2+ 
      mediated signal transduction in neurons. They develop by a periodical interplay
      of Ca2+, which enters the neuron from the extracellular medium and triggers Ca2+
      release from the endoplasmic reticulum (ER). Ca2+ -oscillations are terminated by
      reuptake into the ER or plasmalemmal extrusion. Spontaneous Ca2+ -oscillations
      are glutamate dependent and appear to be responsible for neuronal plasticity and
      integration of information. Here, we examined the role of the gamma-aminobutyric
      acid (GABAA) receptor on spontaneous Ca2+ -oscillations and studied the effects
      of the anaesthetics midazolam, thiopental and the non-anesthetic barbituric acid
      on spontaneous Ca2+ -oscillations. METHODS: Hippocampal neuronal cell cultures of
      19-day-old embryonic Wistar rats 17-18 days in culture were loaded with the Ca2+ 
      sensitive dye Fura-2AM. Experiments were performed using dual wave-length
      excitation fluorescence microscopy and calibration constants were obtained from
      in situ calibration. RESULTS: Spontaneous Ca2+ -oscillations are influenced by
      the GABAA receptor. The intravenous anaesthetics midazolam and thiopental
      suppressed the amplitude and frequency reversibly in a dose-dependent manner with
      EC50 in clinically relevant concentrations. This effect was mediated via the
      GABAA receptor as it could be reversed by the GABAA receptor antagonist
      bicuculline. In contrast, the application of barbituric acid had no effects on
      the spontaneous Ca2+ -oscillations. CONCLUSION: Spontaneous Ca2+ -oscillations
      are influenced by the GABAA receptor. Spontaneous Ca2+ -oscillations might
      represent an interesting model system to study anaesthetic mechanisms on neuronal
      information processing.

PMID- 16987372
TI  - Cerebral state index response to incision: a clinical study in day-surgical
      patients.
AB  - BACKGROUND: Inadequate anaesthesia, with somatic/autonomic response or awareness,
      is often revealed at intubation and surgical incision. Anaesthetic depth monitors
      should be able to prevent this risk. This explorative study examined the ability
      of the cerebral state monitor to predict autonomic/somatic responses to incision.
      METHODS: Forty-two ASA I-II day-surgical patients [19 men and 23 females; mean
      age 52 (29-79) years, mean weight 77 (50-118) kg] were induced clinically with
      fentanyl/propofol with sevoflurane after placement of the laryngeal mask airway.
      The cerebral state index (CSI) was blindly recorded 4 min prior to and 4 min
      after incision. RESULTS: During the 4 min prior to incision, the mean CSI was 45
      (16-62) and increased by 9 (-13-40) when the mean value for the first 4 min after
      incision was subtracted from the value prior to incision, corresponding to a
      relative change of 21% (-21-118). The change in CSI did not show any consistent
      relation to the value before incision. Five patients showed minor movements after
      incision and six patients had > 25% increase in blood pressure. Neither CSI nor
      the change in index differed between patients who did or did not respond
      somatically or autonomically to incision. The last CSI value just prior to
      incision was 44 for non-responders and 40 and 42 for somatic and autonomic
      responders, respectively. CONCLUSION: The CSI in the majority of patients was
      within acceptable ranges during clinically adjusted anaesthesia prior to incision
      but seems not to be able to reliably predict an autonomic or somatic response to
      incision.

PMID- 16987373
TI  - Portable ultrasound in pre-hospital emergencies: a feasibility study.
AB  - BACKGROUND: Ultrasound plays a central role in the evaluation of both trauma and
      medical emergencies. The development of portable sonography devices could extent
      its application into the pre-hospital arena. The aim of our study was to evaluate
      feasibility of pre-hospital ultrasound in the Norwegian Air Rescue setting.
      MATERIAL AND METHODS: During a 3-month period, we conducted a prospective study
      using sonography in pre-hospital patient management. All examinations were
      carried out by the same ultrasound-certified physician using a Primedic Handyscan
      in a standardized focused protocol for abdominal and lung sonography and a
      subcostal 2-chamber long axis view. Inclusion criteria were abdominal/thoracic
      and obstetric trauma, circulatory/respiratory compromise, pulseless electric
      activity (PEA) in cardiac arrest, acute abdomen and monitoring during transport.
      Allowed examination time was restricted to 3 min on the scene. The patient's
      gender, age, symptoms, trauma mechanism, quality of visualization and diagnose
      made were recorded. Pre-hospital results were compared with in-hospital findings.
      RESULTS: Thirty-eight patients were entered into the study. Three patients had to
      be excluded due to technical difficulties. Nineteen medical, 15 traumas and 1
      obstetric patient were included. Good visualization was obtained in 74% (n= 26),
      moderate in 26% (n = 9). Median examination time was 2.5 min (range 1-3 min).
      Nine patients (26%) showed positive sonography findings. Sensitivity was 90%,
      specificity 96%. Diagnostic usefulness was high in undetermined cardiac arrest
      and hypotension and massive hematoperitoneum. CONCLUSION: Pre-hospital ultrasound
      when applied by an proficient examiner using a goal-directed, time sensitive
      protocol is feasible, does not delay patient management and provides diagnostic
      and therapeutic benefit. Further studies are warranted to identify the exact
      indications and role of pre-hospital sonography.

PMID- 16987374
TI  - Enoximone in cardiac arrest caused by propranolol: two case reports.
AB  - We report two clinical cases of cardiac arrest, the former due to an adverse
      effect of intravenous (i.v.) propranolol in a patient with systemic sclerosis,
      the latter from a propranolol suicidal overdose. In both cases, conventional
      advanced life support (ALS) was ineffective but both patients eventually
      responded to the administration of enoximone, a phosphodiesterase III (PDE III)
      inhibitor. After the arrest, both patients regained consciousness and were
      discharged home. The chronotropic and inotropic effects of PDE III inhibitors are
      due to inhibition of intracellular PDEIII and are therefore unaffected by beta
      blockers. These cases suggest that PDEIII inhibitors may be useful in restoring
      spontaneous circulation in cardiac arrest associated with beta-blocker
      administration when standard ALS is ineffective.

PMID- 16987375
TI  - Multimodal cerebral monitoring and decompressive surgery for the treatment of
      severe bacterial meningitis with increased intracranial pressure.
AB  - Bacterial meningitis is still associated with a high mortality, mainly because of
      cerebral herniation as a result of increased intracranial pressure. Published
      data stress the necessity of an early diagnosis and immediate start of antibiotic
      therapy. Nevertheless, there are only few reports in which therapeutic strategy
      was based on the monitoring and the reduction of intracranial pressure (ICP). We
      report one case of bacterial meningitis caused by Neisseria meningitidis with an
      initial ICP value of 60 mmHg, which was treated by large hemicraniectomy and
      ventriculostomy, leading to a favorable neurological long-term result. The
      surgical decision was accelerated by an accurate ICP evaluation based on cerebral
      monitoring [transcranial Doppler ultrasonography (TCD) and intracranial ICP
      device]. In selected patients with bacterial meningitis and clinical and
      radiological evidence of elevated ICP, cerebral monitoring and aggressive
      reduction of ICP may be crucial to improve survival and neurological outcome.
      When maximal medical ICP treatment fails to reduce severe intracranial
      hypertension, decompressive craniectomy should be rapidly proposed.

PMID- 16987376
TI  - Management of near fatal blunt laryngeal trauma.
AB  - Blunt laryngeal trauma is uncommon, difficult to diagnose and recommended
      assessment and management guidelines differ. Mortality can be as high as 40%.
      Initial symptoms might mask the seriousness of the injury and a history of trauma
      is important. This report describes a case which illustrates many of the
      difficulties encountered. A high index of suspicion is needed, and all patients
      with a suspected blunt laryngeal injury, even with minor symptoms, should be
      taken seriously and considered for early precautionary airway intervention.

PMID- 16987377
TI  - Beneficial outcome after prostaglandin-induced post-partum cardiac arrest using
      levosimendan and extracorporeal membrane oxygenation.
AB  - BACKGROUND: Administration of high doses of prostaglandins is a frequently
      performed and effective method for the treatment of atonic uterine haemorrhage in
      order to increase uterine muscle tone. Rarely, however, these drugs may cause
      life-threatening complications including bronchospasm, acute pulmonary oedema and
      myocardial infarction caused by coronary spasms. METHODS: We discuss the
      management of a patient suffering post-partum atonic uterine bleeding,
      catecholamine-resistant cardiac arrest and fulminant pulmonary failure due to
      deleterious side-effects of treatment with prostaglandins. RESULTS: During
      therapy resistant cardiopulmonary resuscitation, the addition of levosimendan to
      standard medications resulted in a prompt stabilization of haemodynamics.
      Subsequent treatment of pulmonary failure was successfully managed with ECMO.
      CONCLUSION: Although levosimendan is not approved for pharmacological treatment
      of cardiopulmonary arrest, the beneficial effects in this patient suggest an
      important role of calcium sensitization and vasodilation during prostaglandin
      induced cardiac arrest.

PMID- 16987378
TI  - "Guilty culprit or innocent bystander?".

PMID- 16987379
TI  - Adenosine-induced ventricular tachycardia.

PMID- 16987380
TI  - Risk-stratifying Jervell and Lange-Nielsen syndrome from clinical data.

PMID- 16987381
TI  - Effect of cardiac resynchronization therapy in patients with moderate left
      ventricular systolic dysfunction and wide QRS complex: a prospective study.
AB  - BACKGROUND: We sought to investigate the effect of cardiac resynchronization
      therapy (CRT) on disease progression in patients with moderate left ventricular
      (LV) systolic dysfunction. METHODS AND RESULTS: This is a prospective study to
      explore the effect of CRT in 15 optimally treated patients (age: 66.1 +/- 12.8
      years; male = 13) with New York Heart Association (NYHA) class III, LV ejection
      fraction >35% and <45% and QRS duration >120 msec. Echocardiographic examination
      and standard heart failure assessment was performed before and 3 months after CRT
      implantation. The magnitude of echocardiographic remodeling measurements was
      compared with 30 age, sex, NYHA class, and heart failure etiology matched
      patients with conventional CRT indication. There were significant reductions in
      LV end-systolic (86.2 +/- 24.1 to 69.7 +/- 22.2 mL, P < 0.01)/end-diastolic
      (135.5 +/- 36.8 to 120.5 +/- 34.6 mL, P < 0.01) volumes, improvement in LV
      ejection fraction (39.1 +/- 2.2 to 44.2 +/- 5.5%, P = 0.01), and NYHA class (3.0
      +/- 0.0 to 2.07 +/- 0.46, P < 0.001). There was no difference in changes in LV
      volumes, ejection fraction, NYHA class, and exercise capacity before and after
      CRT between the study and conventional groups except for greater improvement in
      the quality of life score in the conventional group. CONCLUSION: In this
      prospective study, significant LV reverse remodeling by CRT in those with a wide
      QRS complex and moderate LV systolic dysfunction was observed. Further studies to
      explore the benefit of CRT in patients with less severe heart failure are
      recommended.

PMID- 16987382
TI  - Rapid detection and successful treatment of esophageal perforation after
      radiofrequency ablation of atrial fibrillation: lessons from five cases.
AB  - INTRODUCTION: The aim of the study was to identify criteria for rapid recognition
      and successful treatment of esophageal perforation after radiofrequency ablation
      for atrial fibrillation (AF). METHODS AND RESULTS: Esophageal perforation
      occurred in five patients after intraoperative (n = 4) or percutaneous (n = 1) AF
      ablation. Patients presented with high fever (n = 3) or severe chest/epigastric
      pain (n = 2) 8-28 days after ablation. WBC count was elevated at presentation in
      all patients (15,460 +/- 2,910/muL), CRP showed a delayed rise. Thoracic CT
      detected free air in all. Neurologic complications occurred in three cases (60%)
      with a delay of 5-40 hours after first symptoms. Only one (20%) developed
      neurologic complications within the first 24 hours. Two patients (40%) died
      before surgery could be performed. In both, time from symptom onset to diagnosis
      was significant (24 and 36 hours). Three patients (60%) underwent esophageal
      resection and survived. In two of them, treatment was rapid with time from
      symptoms to surgery of 24 hours; they had favorable outcome. In the third
      surviving patient, surgery was late (5 days after first symptoms); permanent
      neurologic residues remained. CONCLUSION: The leading symptom of esophageal
      perforation is high fever or severe chest/epigastric pain. Fever is not
      necessarily present. Leukocytosis is the earliest and most sensitive laboratory
      marker, thoracic CT the most valuable diagnostic examination. The dramatic
      neurologic complications occur with a delay of at least a few hours after first
      symptoms. Immediate surgery may prevent neurologic complications and could
      possibly result in a high survival rate without residues. Delay of treatment
      seems to have devastating results.

PMID- 16987383
TI  - Multilevel block between pulmonary venous tachycardia and left atrium as a cause
      of regular tachycardia.

PMID- 16987384
TI  - Event-recorder monitoring in the diagnosis of atrial fibrillation in symptomatic
      patients: subanalysis of the SOPAT trial.
AB  - In the SOPAT (suppression of paroxysmal atrial tachyarrhythmias) trial, a high
      number of asymptomatic atrial fibrillation (AF) episodes were registered in
      patients with symptomatic AF. This subanalysis was performed to answer three
      questions: (1) Does antiarrhythmic therapy influence the ratio of symptomatic to
      asymptomatic AF? (2) Are symptoms during AF dependent on the heart rate (HR)? (3)
      Do symptoms correlate with an episode of AF? Within 60 months 1,033 patients with
      symptomatic AF were randomized to either quinidine plus verapamil (Q+V) 480/240
      mg/day, Q+V 320/160 mg/day, sotalol 320 mg/day, or placebo, and followed up by
      daily and symptom-triggered ECG event recording. Over 188,634 ECGs were analyzed
      (87% SR, 7% AF). Symptoms were reported in only 46% of AF-ECGs. Quinidine plus
      verapamil reduced the ratio of symptomatic to asymptomatic AF, whereas sotalol
      had no effect (median [%] (25/75% quartile): Q+V 480/240: 33 (0/79), Q+V 320/160:
      45 (1/82), sotalol: 56 (7/93), placebo: 63 (8/92)). The HR during AF directly
      correlates with the occurrence of symptoms (P < 0.001) and was significantly
      lower during asymptomatic AF in all groups (mean +/- SD: sympt.: 113 +/-
      27/minute, asympt.: 103 +/- 27/minute, P < 0.001). Both antiarrhythmics reduced
      the mean HR compared to placebo (P < 0.001). Analyzing all symptom-triggered
      ECGs, AF was diagnosed in only 37%, whereas the majority were SR. Taken together,
      in contrast to sotalol, Q+V reduces the ratio of symptomatic to asymptomatic AF
      compared with placebo, at least in part by decreasing the heart rate.
      Furthermore, patients' symptoms are not a reliable surrogate parameter for the
      prevalence of AF.

PMID- 16987386
TI  - Re: Catheter ablation of right ventricular outflow tract.

PMID- 16987389
TI  - Persistence of antibodies in blood and body fluids in decaying fox carcasses, as
      exemplified by antibodies against Microsporum canis.
AB  - To assist in evaluating serological test results from dead animals, 10 silver
      foxes (Vulpes vulpes) and 10 blue foxes (Alopex lagopus), 6 of each species
      previously vaccinated against and all challenged with Microsporum canis, were
      blood sampled and euthanased. Fox carcasses were stored at +10 degrees C, and
      autopsy was performed on Days 0, 2, 4, 7, and 11 post mortem during which samples
      from blood and/or body fluid from the thoracic cavity were collected. Antibodies
      against M. canis were measured in an enzyme-linked immunosorbent assay (ELISA) as
      absorbance values (optical density; OD). To assess the degradation of antibodies,
      the ratio between post mortem and ante mortem absorbance was calculated. The mean
      absorbance from samples collected during autopsy was generally lower than from
      samples from live animals. In blood samples, this difference increased
      significantly with time (P = 0.04), while in body fluid samples the difference
      decreased (not significant; P = 0.18). We suggest that a positive serological
      result from testing blood or body fluid of a dead animal may be regarded as
      valuable, although specific prevalences obtained by screening populations based
      on this type of material may represent an under-estimation of the true antibody
      prevalence. Negative serological test results based on material from carcasses
      may be less conclusive, taken into account the general degradation processes in
      decaying carcasses, also involving immunoglobulin proteins.

PMID- 16987390
TI  - Mastitis and related management factors in certified organic dairy herds in
      Sweden.
AB  - BACKGROUND: Mastitis is one of the major threats to animal health, in organic
      farming as well as conventional. Preliminary studies of organic dairy herds have
      indicated better udder health in such herds, as compared to conventional herds.
      The aim of this paper was to further study mastitis and management related
      factors in certified organic dairy herds. METHODS: An observational study of 26
      certified organic dairy herds in mid-eastern Sweden was conducted during one
      year. A large-animal practitioner visited the herds three times and clinically
      examined and sampled cows, and collected information about general health and
      management routines. Data on milk production and disorders treated by a
      veterinarian in the 26 herds, as well as in 1102 conventional herds, were
      retrieved from official records. Multivariable logistic regression was used to
      assess associations between herd type (organic vs. conventional) and incidence of
      disorders. RESULTS: The organic herds that took part in the study ranged in size
      from 12 to 64 cows, in milk production from 3772 to 10,334 kg per cow and year,
      and in bulk milk somatic cell counts from 83,000 to 280,000 cells/ml. The organic
      herds were found to have a lower incidence of clinical mastitis, teat injuries,
      and a lower proportion of cows with a high somatic cell count (as indicated by
      the UDS, Udder Disease Score) compared to conventional herds. The spectrum of
      udder pathogenic bacteria was similar to that found in other Swedish studies.
      Treatment of mastitis was found to be similar to what is practised in
      conventional herds. Homeopathic remedies were not widely used in the treatment of
      clinical mastitis.The calves in most of these organic herds suckled their dams
      for only a few days, which were not considered to substantially affect the udder
      health. The main management factor that was different from conventional herds was
      the feeding strategy, where organic herds used a larger share of forage.
      CONCLUSION: Udder health in Swedish organic herds appears to be better than in
      conventional herds of comparable size and production. The major difference in
      management between the two types of farms is the proportion of concentrates fed.
      The mechanisms explaining the association between intensity of feeding and udder
      health in dairy cows require further research.

PMID- 16987391
TI  - A preliminary study on the induction of dioestrous ovulation in the mare--a
      possible method for inducing prolonged luteal phase.
AB  - BACKGROUND: Strong oestrous symptoms in the mare can cause problems with racing,
      training and handling. Since long-acting progesterone treatment is not permitted
      in mares at competition (e.g. according to FEI rules), there is a need for
      methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the
      late luteal phase may cause a prolongation of the luteal phase in mares. METHODS:
      In this preliminary study, in an attempt to induce ovulation during the luteal
      phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly
      in four mares (experimental group) in the luteal phase when a dioestrous follicle
      > or = 30 mm was detected. A fifth mare included in this group was not treated
      due to no detectable dioestrous follicles > or = 30 mm. Four control mares were
      similarly injected with saline. The mares were followed with ultrasound for 72
      hours post injection or until ovulation. Blood samples for progesterone analysis
      were obtained twice weekly for one month and thereafter once weekly for another
      two to four months. RESULTS: Three of the hCG-treated mares ovulated within 72
      hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days
      respectively. One treated mare never ovulated after the hCG injection and
      progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone
      levels in the control mares were below 3 nmol/l within nine days after saline
      injection, except for one mare, which developed a spontaneously prolonged luteal
      phase of 72 days. CONCLUSION: HCG treatment may be a method to induce prolonged
      luteal phases in the mare provided there is a dioestrous follicle > or = 30 mm
      that ovulates post-treatment. However, the method needs to be tested on a larger
      number of mares to be able to draw conclusions regarding its effectiveness.

PMID- 16987392
TI  - Physiological routes from intra-uterine seminal contents to advancement of
      ovulation.
AB  - Whole boar semen or seminal plasma has been demonstrated to advance the time of
      ovulation in gilts. As a means of clarifying this influence, the contribution of
      uterine lymphatics and their white cell populations has been examined. After duct
      visualisation with Evan's blue, lymph was sampled from a mesometrial vessel in
      eight pre-ovulatory gilts whose uterine lumen was infused simultaneously with
      whole semen in one ligated horn and saline in the contralateral ligated horn.
      Lymph was collected from cannulated vessels for periods of up to four hours under
      general anaesthesia. Thereafter, mesometrial lymph nodes, utero-tubal junction
      and uterine wall tissues were sampled. The proportion of nucleated cells in the
      sampled lymph increased towards the end of the collection period, but
      erythrocytes were found in all instances preventing a meaningful differentiation
      and identification of leukocytes. Prominent uterine lymph nodes were present in
      the mesometrium on both sides of the reproductive tract in 7 of 10 gilts.
      Differences in cellular contents were demonstrated between the side of the tract
      infused with semen and that infused with saline control. Two of 4 gilts had lower
      values for CD4 (Cluster Differentiation) and 3 of 6 gilts higher values for MHC
      II (Major Histocompatibility Complex) markers on the side challenged with semen.
      In contrast, values remained constant for CD8 but ranged widely for CD18.
      Immunohistochemical analysis of uterine tissue samples for MHC II+ cells revealed
      significant differences (P < 0.05) between the control and semen-treated ligated
      portions of the horns, as well as between the tissue sample of uterine wall and
      that from the utero-tubal junction, but there were no significant differences for
      CD4+ cells. It therefore remains plausible that semen-induced cytokines in the
      uterine lymph undergo counter-current transfer to the ipsilateral ovary and
      accelerate the final maturation of pre-ovulatory Graafian follicles.

PMID- 16987393
TI  - Fertility of frozen-thawed stallion semen cannot be predicted by the currently
      used laboratory methods.
AB  - The aim of the project was to use current simple and practical laboratory tests
      and compare results with the foaling rates of mares inseminated with commercially
      produced frozen semen. In Exp. 1, semen was tested from 27 and in Exp. 2 from 23
      stallions; 19 stallions participated in both experiments. The mean number of
      mares per stallion in both experiments was 37 (min. 7, max. 121). Sperm
      morphology was assessed and bacterial culture performed once per stallion. In
      Exp. 1, progressive motility after 0, 1, 2, 3, and 4 h of incubation using light
      microscopy, motility characteristics measured with an automatic sperm analyzer,
      plasma membrane integrity using carboxyfluorescein diacetate/propidium iodide
      (CFDA/PI) staining and light microscopy, plasma membrane integrity using PI
      staining and a fluorometer, plasma membrane integrity using a resazurin reduction
      test, and sperm concentration were evaluated. In Exp. 2, the same tests as in
      Exp. 1 and a hypo-osmotic swelling test (HOST) using both light microscopy and a
      fluorometer were performed immediately after thawing and after a 3-h incubation.
      Statistical analysis was done separately to all stallions and to those having >
      or = 20 mares; in addition, stallions with foaling rates < 60 or > or = 60% were
      compared. In Exp. 1, progressive motility for all stallions after a 2-4-h
      incubation correlated with the foaling rate (correlation coefficients 0.39-0.51),
      (p < 0.05). In stallions with > 20 mares, the artificial insemination dose showed
      a correlation coefficient of -0.58 (p < 0.05). In Exp. 2, the HOST immediately
      after thawing showed a negative correlation with foaling rate (p < 0.05). No
      single test was consistently reliable for predicting the fertilizing capacity of
      semen, since the 2 experiments yielded conflicting results, although the same
      stallions sometimes participated in both. This shows the difficulty of frozen
      semen quality control in commercially produced stallion semen, and on the other
      hand, the difficulty of conducting fertility trials in horses.

PMID- 16987394
TI  - Contributions to variability of clinical measures for use as indicators of udder
      health status in a clinical protocol.
AB  - A cross-sectional observational study with repeated observations was conducted on
      16 Danish dairy farms to quantify the influence of observer, parity, time (stage
      in lactation) and farm on variables routinely selected for inclusion in clinical
      protocols, thereby to enable a more valid comparison of udder health between
      different herds. During 12 months, participating herds were visited 5 times by
      project technicians, who examined 20 cows and scored the selected clinical
      variables. The estimates of effect on variables were derived from a random
      regression model procedure. Statistical analyses revealed that, although
      estimates for occurrence of several the variables, e.g. degree of oedema, varied
      significantly between observers, the effects on many of these estimates were
      similar in size. Almost all estimates for occurrences of variables were
      significantly affected either parity and lactation stage, or by both e.g. udder
      tissue consistency. Some variables, e.g. mange, had high estimates for the farm
      component, and others e.g. teat skin quality had a high individual component.
      Several of the variables, e.g. wounds on warts, had a high residual component
      indicating that a there still was a major part of the variation in data, which
      was unexplained. It was concluded that most of the variables were relevant for
      implementation in herd health management, but that adjustments need to be made to
      improve reliability.

PMID- 16987395
TI  - Iron and iron/manganese ratio in forage from Icelandic sheep farms: relation to
      scrapie.
AB  - This study was undertaken in order to examine whether any connection existed
      between the amounts of iron in forage and the sporadic occurrence of scrapie
      observed in certain parts of Iceland. As iron and manganese are considered
      antagonistic in plants, calculation of the Fe/Mn ratios was also included by
      using results from Mn determination earlier performed in the same samples. Forage
      samples (n = 170) from the summer harvests of 2001-2003, were collected from 47
      farms for iron and manganese analysis. The farms were divided into four
      categories: 1. Scrapie-free farms in scrapie-free areas (n = 9); 2. Scrapie-free
      farms in scrapie-afflicted areas (n = 17); 3. Scrapie-prone farms (earlier
      scrapie-afflicted, restocked farms) (n = 12); 4. Scrapie-afflicted farms (n = 9).
      Farms in categories 1 and 2 are collectively referred to as scrapie-free farms.
      The mean iron concentration in forage samples from scrapie-afflicted farms was
      significantly higher than in forage samples from farms in the other scrapie
      categories (P = 0.001). The mean Fe/Mn ratio in forage from scrapie-afflicted
      farms was significantly higher than in forage from scrapie-free and scrapie-prone
      farms (P < 0.001). The results indicated relative dominance of iron over
      manganese in forage from scrapie-afflicted farms as compared to farms in the
      other categories. Thus thorough knowledge of iron, along with manganese, in soil
      and vegetation on sheep farms could be a pivot in studies on sporadic scrapie.

PMID- 16987396
TI  - Impact of coccidial infection on vaccine- and vvIBDV in lymphoid tissues of SPF
      chickens as detected by RT-PCR.
AB  - BACKGROUND: This study aimed at investigating a potential effect caused by
      coccidia on the immune response to vaccine- and very virulent infectious bursal
      disease virus (vvIBDV) in SPF chickens. METHODS: Two groups of three weeks old
      SPF chickens were vaccinated prior to inoculation with coccidia and challenge
      with virulent IBDV, all within a period of eight days. Two control groups were
      similarly treated, except that challenge with field virus was omitted in one
      group while inoculation with coccidia was omitted in the other group. Clinical
      signs, lesions in the intestines caused by coccidia, lesions in the bursa of
      Fabricius caused by IBDV, IBDV-antibody titres, and virus detection by reverse
      transcription polymerase chain reaction (RT-PCR) were compared among the groups.
      Lymphoid tissues and swab samples were analysed by general RT-PCR, and positive
      results were identified by strain specific duplex (DPX) RT-PCR. RESULTS: In the
      triple-infected groups, vaccine strain IBDV was detected in spleen and thymus
      tissues, and no field virus was detected in bursa samples, contrary to the double
      infected groups. CONCLUSION: The results suggest an enhancing effect on the
      immune response caused by subclinical coccidiosis and vvIBDV acting in concert.

PMID- 16987397
TI  - Pelodera (syn. Rhabditis) strongyloides as a cause of dermatitis--a report of 11
      dogs from Finland.
AB  - BACKGROUND: Pelodera (Rhabditis) strongyloides is a small saprophytic nematode
      that lives in decaying organic matter. On rare occasions, it can invade the
      mammalian skin, causing a pruritic, erythematous, alopecic and crusting
      dermatitis on skin sites that come into contact with the ground. Diagnosis of the
      disease is based on case history (a dog living outdoors on damp straw bedding)
      with characteristic skin lesions and on the demonstration of typical larvae in
      skin scrapings or biopsy. Pelodera (rhabditic) dermatitis cases have been
      reported mainly from Central European countries and the United States. CASE
      PRESENTATION: During 1975-1999, we verified 11 canine cases of Pelodera
      dermatitis in Finland. The cases were confirmed by identifying Pelodera larvae in
      scrapings. Biopsies for histopathology were obtained from three cases, and
      typical histopathological lesions (epidermal hyperplasia, epidermal and
      follicular hyperkeratosis, folliculitis and furunculosis with large numbers of
      nematode larvae of 25-40 microm of diameter within hair follicles) were present.
      The Pelodera strongyloides dermatitica strain from the first verified case in
      Finland has been maintained in ordinary blood agar in our laboratory since 1975.
      Light microscopy (LM) and scanning electron microscopy (SEM) studies were
      employed to obtain detailed morphological information about the causative agent.
      The rhabditiform oesophagus at all developmental stages, the morphology of the
      anterior end of the nematode, copulatory bursa and spicules of the male and the
      tail of the female were the most important morphological features for identifying
      P. strongyloides. CONCLUSION: These cases show that Pelodera dermatitis occurs in
      Finland, and also farther north than described earlier in the literature. This
      condition should be considered when a dog living outdoors has typical skin
      lesions situated at sites in contact with the ground as the main presenting
      clinical feature. The fastest and easiest way to confirm the diagnosis is to
      demonstrate typical larvae in skin scrapings. In uncertain cases, skin biopsy and
      culturing of the worms are recommended as supplementary diagnostic procedures.

PMID- 16987398
TI  - Efficacy of live B1 or Ulster 2C Newcastle disease vaccines simultaneously
      vaccinated with inactivated oil adjuvant vaccine for protection of Newcastle
      disease virus in broiler chickens.
AB  - Two hundred, one-day-old broiler chicks were divided into groups 1, 2 and 3
      containing 60, 70 and 70 chicks, respectively. The groups were divided into
      subgroups of 10 chicks that were vaccinated according to the following scheme:
      group 1 unvaccinated control, group 2 vaccinated subcutaneously at 1 day old with
      inactivated oil adjuvant vaccine (IOAV) in combination with live B1 vaccine.
      Group 3 was vaccinated in the same mode as group 2 with IOAV and live Ulster 2C
      vaccine. All birds were challenged when they were 28 days old. Mortality rate,
      body weight gain and feed conversion ratio (FCR) were monitored before and after
      challenge. All the chickens in group 1 died, indicating that there was no disease
      resistance of this unvaccinated control group of chickens. Conversely, the
      monitored disease resistance of chickens in groups 2 and 3 was 68.57% +/- 18.64
      and 88.57% +/- 9.00, respectively (P < 0.05). The morbidity of chickens in groups
      2 and 3 was 37.89% +/- 14.36 and 14.76% +/- 12.40, respectively (P < 0.05). The
      body weight gain, feed intake and FCR of group 3 were significantly better than
      those of group 2 (P < 0.05) during 1-42 days old. The simultaneous vaccination
      with B1 or Ulster 2C and IOAV of 1-day-old chicks gave some protection of 28-day
      old broilers without a booster vaccination.

PMID- 16987399
TI  - Summer eczema in exported Icelandic horses: influence of environmental and
      genetic factors.
AB  - A cross sectional study was designed to estimate the prevalence of summer eczema
      (a chronic, recurrent seasonal dermatitis) in exported Icelandic horses and the
      influence of environmental and genetic factors on the development of the disease.
      Among 330 horses, which had been exported to Germany, Denmark and Sweden, 114
      (34.5%) were found to have clinical signs of summer eczema. The prevalence was
      highest 2 years after export and the exposure to the biting midges Culicoides
      spp., was found to be the main risk factor for developing the disease. Genetic
      influence on the sensitivity for the disease was not established. It was
      concluded that exported Icelandic horses are predisposed for summer dermatitis
      and the fact that they are not introduced to the antigens of the biting midges
      early in live, due to it's absence in Iceland, is likely to explain the high
      prevalence of the disease after export.

PMID- 16987400
TI  - Intestinal carriage of Campylobacter jejuni and Campylobacter coli among cattle
      from south-western Norway and comparative genotyping of bovine and human isolates
      by amplified-fragment length polymorphism.
AB  - In a survey conducted in 1999-2001, the carriage of thermotolerant Campylobacters
      in cattle was investigated, and the genetic diversity of C. jejuni within one
      herd was examined and compared with human isolates. C. jejuni, C. coli and other
      thermotolerant Campylobacter spp. were isolated from intestinal contents from
      26%, 3% and 2% of 804 cattle, respectively. The carriage rate was higher in
      calves (46%) than in adults (29%). Twenty-nine C. jejuni isolates from one herd
      and 31 human isolates from the study area were genotyped with amplified-fragment
      length polymorphism (AFLP). Eighty-three % of the bovine isolates fell into three
      distinct clusters with 95-100% similarity, persistent in the herd for 5-10
      months. Among human isolates, 58% showed >90% similarity with bovine isolates.
      The results show that cattle are a significant and stable reservoir for C. jejuni
      in the study area. Transmission between individuals within the herd may be
      sufficient to maintain a steady C. jejuni population independent of environmental
      influx. The results of this study have provided new information on C. jejuni and
      C. coli transmission, and also on the carriage in cattle, genotypes stability and
      similarity between bovine and human isolates.

PMID- 16987401
TI  - Insulin-like growth factor-I (IGF-I) and thioredoxin are differentially expressed
      along the reproductive tract of the ewe during the oestrous cycle and after
      ovariectomy.
AB  - Insulin-like growth factor-I (IGF-I) and thioredoxin are regulated by gonadal
      steroids in the female reproductive tract of many species. Oestradiol regulates
      IGF-I and thioredoxin mRNA levels in the reproductive tract of prepubertal lambs.
      The physiological status (different endocrine environment) may affect the
      sensitivity of the reproductive tract to oestradiol and progesterone. We studied
      the effects of different endocrine milieus (late-follicular and luteal phases of
      the oestrous cycle, and ovariectomy before or after puberty) on the expression of
      IGF-I, thioredoxin, oestrogen receptor alpha (ER alpha) and progesterone receptor
      (PR) in sheep. The mRNA levels were determined by a solution hybridisation
      technique. In the uterus the levels of ER alpha, PR and thioredoxin mRNA were
      higher in the late-follicular phase group than in the other three groups, and IGF
      I mRNA was high during both the late-follicular and the luteal phases. In the
      cervix only PR mRNA was significantly higher in the ewes in the late-follicular
      phase than in the other groups. In the oviducts the levels of thioredoxin and ER
      alpha mRNA were highest in the ovariectomised adult ewes, and thioredoxin mRNA
      was higher than the levels found in the ewes in the late-follicular phase. The
      IGF-I mRNA levels in the oviduct did not differ between any of the groups. The
      transcripts of IGF-I, thioredoxin, ER alpha and PR, varied according to the
      physiological status and also along the female reproductive tract, suggesting
      that the regulation of the mRNA levels of these factors by the steroid
      environment is tissue specific.

PMID- 16987402
TI  - The first report of Aelurostrongylus falciformis in Norwegian badgers (Meles
      meles).
AB  - The first report of Aelurostrongylus falciformis (Schlegel 1933) in Fennoscandian
      badgers is described. Routine parasitological examination of nine Norwegian
      badgers, at the National Veterinary Institute during 2004 and 2005, identified A.
      falciformis in the terminal airways of five of the animals. The first stage
      larvae (L1) closely resembled, in size and morphology, those of Angiostrongylus
      vasorum (Baillet 1866). The diagnosis for both A. falciformis and A. vasorum is
      frequently based on the identification of L1 in faeces or sputum. The potential
      for misclassification of an A. falciformis infection as A. vasorum, where larval
      identification is the only diagnostic method used, is discussed.

PMID- 16987403
TI  - Campylobacter spp., Enterococcus spp., Escherichia coli, Salmonella spp.,
      Yersinia spp., and Cryptosporidium oocysts in semi-domesticated reindeer
      (Rangifer tarandus tarandus) in Northern Finland and Norway.
AB  - The specific aim of this study was to assess the faecal shedding of zoonotic
      enteropathogens by semi-domesticated reindeer (Rangifer tarandus tarandus) to
      deduce the potential risk to human health through modern reindeer herding. In
      total, 2,243 faecal samples of reindeer from northern regions of Finland and
      Norway were examined for potentially enteropathogenic bacteria (Campylobacter
      species, Enterococcus species, Escherichia coli, Salmonella species and Yersinia
      species) and parasites (Cryptosporidium species) in accordance with standard
      procedures. Escherichia coli were isolated in 94.7%, Enterococcus species in
      92.9%, Yersinia species in 4.8% of the samples and Campylobacter species in one
      sample only (0.04%). Analysis for virulence factors in E. coli and Yersinia
      species revealed no pathogenic strains. Neither Salmonella species nor
      Cryptosporidium oocysts were detected. The public health risk due to reindeer
      husbandry concerning zoonotic diseases included in this study has to be
      considered as very low at present but a putative epidemiological threat may arise
      when herding conditions are changed with respect to intensification and crowding.

PMID- 16987404
TI  - Canine atopic dermatitis: validation of recorded diagnosis against practice
      records in 335 insured Swedish dogs.
AB  - A cross-sectional study of insured Swedish dogs with a recorded diagnosis of
      canine atopic dermatitis (CAD) was performed. In order to validate the
      correctness of this specific diagnosis in the insurance database, medical records
      were requested by mail from the attending veterinarians. All dogs with a
      reimbursed claim for the disease during 2002 were included in the original study
      sample (n = 373). Medical records were available for 335 individuals (response
      rate: 89.8%). By scrutinizing the submitted records it was determined that all
      dogs had been treated for dermatologic disease, and that 327 (97.6%) could be
      considered to have some allergic skin disease. However, as information regarding
      dietary trial testing was missing in many dogs the number that were truly atopic
      could not be determined. The clinical presentation and nature of test diet for
      dogs with or without response to dietary trial testing was compared for a subset
      of 109 individuals that had undergone such testing. The only significant
      difference between these two groups was that the proportion of dogs with reported
      gastrointestinal signs was higher in the group that subsequently responded to a
      diet trial. In conclusion, the agreement between the recorded diagnosis in the
      insurance database and the clinical manifestations recorded in the submitted
      medical records was considered acceptable. The concern was raised that many
      attending veterinarians did not exclude cutaneous adverse food reactions before
      making the diagnosis of CAD.

PMID- 16987405
TI  - Use of serum C-reactive protein as an early marker of inflammatory activity in
      canine type II immune-mediated polyarthritis: case report.
AB  - BACKGROUND: Monitoring systemic inflammatory activity during steroid therapy of
      canine immune-mediated polyarthritis (IMPA) is difficult and mainly relies on
      clinical signs. CASE PRESENTATION: Canine serum C-reactive protein (CRP) was
      measured serially and blinded during a 27-week follow-up period of a case of
      Anaplasma phagocytophilia induced type II immune-mediated polyarthritis.
      CONCLUSION: WBC was, as expected, observed not to reflect the inflammatory
      activity during steroid treatment in a clinical useful manner, whereas, CRP is
      suggested a valuable unbiased marker of inflammatory activity during steroid
      treatment in this case.

PMID- 16987406
TI  - MicroArray Facility: a laboratory information management system with extended
      support for Nylon based technologies.
AB  - BACKGROUND: High throughput gene expression profiling (GEP) is becoming a routine
      technique in life science laboratories. With experimental designs that repeatedly
      span thousands of genes and hundreds of samples, relying on a dedicated database
      infrastructure is no longer an option.GEP technology is a fast moving target,
      with new approaches constantly broadening the field diversity. This technology
      heterogeneity, compounded by the informatics complexity of GEP databases, means
      that software developments have so far focused on mainstream techniques, leaving
      less typical yet established techniques such as Nylon microarrays at best
      partially supported. RESULTS: MAF (MicroArray Facility) is the laboratory
      database system we have developed for managing the design, production and
      hybridization of spotted microarrays. Although it can support the widely used
      glass microarrays and oligo-chips, MAF was designed with the specific
      idiosyncrasies of Nylon based microarrays in mind. Notably single channel
      radioactive probes, microarray stripping and reuse, vector control hybridizations
      and spike-in controls are all natively supported by the software suite.
      MicroArray Facility is MIAME supportive and dynamically provides feedback on
      missing annotations to help users estimate effective MIAME compliance. Genomic
      data such as clone identifiers and gene symbols are also directly annotated by
      MAF software using standard public resources. The MAGE-ML data format is
      implemented for full data export. Journalized database operations (audit
      tracking), data anonymization, material traceability and user/project level
      confidentiality policies are also managed by MAF. CONCLUSION: MicroArray Facility
      is a complete data management system for microarray producers and end-users.
      Particular care has been devoted to adequately model Nylon based microarrays. The
      MAF system, developed and implemented in both private and academic environments,
      has proved a robust solution for shared facilities and industry service providers
      alike.

PMID- 16987407
TI  - Pain in veterans of the Gulf War of 1991: a systematic review.
AB  - BACKGROUND: Veterans of the Persian Gulf War of 1991 have reported a range of
      adverse health symptoms. This systematic review aims to identify all studies that
      have compared the prevalence of symptoms of pain in veterans of the Gulf War to
      that in a non-Gulf military comparison group, and to determine whether Gulf War
      veterans are at increased risk of reporting pain. METHODS: 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 reported the prevalence
      of any symptom or condition that included the word "pain" in Gulf War veterans
      and in a comparison group of non-Gulf veterans. 2401 abstracts were independently
      reviewed by two authors. RESULTS: Twenty studies fulfilled the inclusion
      criteria. Five main sites of pain were identified (muscle, joint, chest/heart,
      back and abdominal pain) and separate meta-analyses were performed to summarise
      the results related to each site. A greater proportion of Gulf veterans reported
      symptoms at each site of pain when compared to a non-Gulf military group. Gulf
      deployment was most strongly associated with abdominal pain, with Gulf veterans
      being more than three times more likely to report such pain than a comparison
      group (OR 3.23; 95% CI 2.31-4.51). Statistical heterogeneity between study
      estimates was significant, probably due to variation in measured periods of
      prevalence and symptom measurement methods. CONCLUSION: A higher proportion of
      veterans of the Persian Gulf War of 1991 reported symptoms of pain than military
      comparison groups. This is consistent with previously demonstrated increased
      reporting of more general symptoms (fatigue, multiple chemical sensitivity, post
      traumatic stress disorder) in these veterans compared with non-Gulf military
      groups. However, the primary studies were heterogeneous and varied greatly in
      quality.

PMID- 16987408
TI  - The complete mitochondrial genome of the common sea slater, Ligia oceanica
      (Crustacea, Isopoda) bears a novel gene order and unusual control region
      features.
AB  - BACKGROUND: Sequence data and other characters from mitochondrial genomes (gene
      translocations, secondary structure of RNA molecules) are useful in phylogenetic
      studies among metazoan animals from population to phylum level. Moreover, the
      comparison of complete mitochondrial sequences gives valuable information about
      the evolution of small genomes, e.g. about different mechanisms of gene
      translocation, gene duplication and gene loss, or concerning nucleotide frequency
      biases. The Peracarida (gammarids, isopods, etc.) comprise about 21,000 species
      of crustaceans, living in many environments from deep sea floor to arid
      terrestrial habitats. Ligia oceanica is a terrestrial isopod living at rocky
      seashores of the european North Sea and Atlantic coastlines. RESULTS: The study
      reveals the first complete mitochondrial DNA sequence from a peracarid
      crustacean. The mitochondrial genome of Ligia oceanica is a circular double
      stranded DNA molecule, with a size of 15,289 bp. It shows several changes in
      mitochondrial gene order compared to other crustacean species. An overview about
      mitochondrial gene order of all crustacean taxa yet sequenced is also presented.
      The largest non-coding part (the putative mitochondrial control region) of the
      mitochondrial genome of Ligia oceanica is unexpectedly not AT-rich compared to
      the remainder of the genome. It bears two repeat regions (4x 10 bp and 3x 64 bp),
      and a GC-rich hairpin-like secondary structure. Some of the transfer RNAs show
      secondary structures which derive from the usual cloverleaf pattern. While some
      tRNA genes are putative targets for RNA editing, trnR could not be localized at
      all. CONCLUSION: Gene order is not conserved among Peracarida, not even among
      isopods. The two isopod species Ligia oceanica and Idotea baltica show a
      similarly derived gene order, compared to the arthropod ground pattern and to the
      amphipod Parhyale hawaiiensis, suggesting that most of the translocation events
      were already present the last common ancestor of these isopods. Beyond that, the
      positions of three tRNA genes differ in the two isopod species. Strand bias in
      nucleotide frequency is reversed in both isopod species compared to other
      Malacostraca. This is probably due to a reversal of the replication origin, which
      is further supported by the fact that the hairpin structure typically found in
      the control region shows a reversed orientation in the isopod species, compared
      to other crustaceans.

PMID- 16987409
TI  - Methodological standards in non-inferiority AIDS trials: moving from adherence to
      compliance.
AB  - BACKGROUND: The interpretation of the results of active-control trials regarding
      the efficacy and safety of a new drug is important for drug registration and
      following clinical use. It has been suggested that non-inferiority and
      equivalence studies are not reported with the same quantitative rigor as
      superiority studies. METHODS: Standard methodological criteria for non
      inferiority and equivalence trials including design, analysis and interpretation
      issues were applied to 18 recently conducted large non-inferiority (15) and
      equivalence (3) randomized trials in the field of AIDS antiretroviral therapy. We
      used the continuity-corrected non-inferiority chi-square to test 95% confidence
      interval treatment difference against the predefined non-inferiority margin.
      RESULTS: The pre-specified non-inferiority margin ranged from 10% to 15%. Only 4
      studies provided justification for their choice. 39% of the studies (7/18)
      reported only intent-to-treat (ITT) analysis for the primary endpoint. When on
      treatment (OT) and ITT statistical analyses were provided, ITT was favoured over
      OT for results interpretation for all but one study, inappropriately in this
      statistical context. All but two of the studies concluded there was "similar"
      efficacy of the experimental group. However, 9/18 had inconclusive results for
      non-inferiority. CONCLUSION: Conclusions about non-inferiority should be drawn on
      the basis of the confidence interval analysis of an appropriate primary endpoint,
      using the predefined criteria for non-inferiority, in both OT and ITT, in
      compliance with the non-inferiority and equivalence CONSORT statement. We suggest
      that the use of the non-inferiority chi-square test may provide additional useful
      information.

PMID- 16987410
TI  - Trunk muscle activity in healthy subjects during bridging stabilization
      exercises.
AB  - BACKGROUND: Trunk bridging exercises are often used as therapeutic exercises for
      lumbopelvic stabilization. These exercises focus on the retraining of muscle
      coordination patterns in which optimal ratios between local segmental stabilizing
      and global torque producing muscle activity are assumed to be essential. However,
      a description of such ratios is lacking. The purpose of this study was to
      investigate both relative (as a percentage of maximal voluntary isometric
      contraction) muscle activity levels and ratios of local to global muscle
      activity, during bridging stabilization exercises. METHODS: Thirty healthy
      university students (15 men, 15 women) with a mean age of 19.6 year volunteered
      to perform 3 bridging exercises (single bridging, ball bridge and unilateral
      bridging). The surface electromyographic activity of different trunk muscles was
      evaluated on both sides. RESULTS: During all bridging exercises, the ratio of the
      internal oblique to the rectus abdominis was very high due to minimal relative
      activity of the rectus abdominis. In general, the ratio of the internal/external
      abdominal oblique activity was about 1. However, during the unilateral bridging
      exercise, the ipsilateral internal/external abdominal oblique activity ratio was
      2.79 as a consequence of the significant higher relative activity of the internal
      oblique compared to the external oblique. The relative muscle activity and the
      ratios of the back muscles demonstrated similar activity levels for all back
      muscles, resulting in ratios about 1. CONCLUSION: Both the minimal relative
      activity of the rectus abdominis and the high internal oblique to the rectus
      abdominis activity ratio reported in the present study are in accordance with
      results of other trunk stabilization exercises. The relative muscle activity and
      the ratio of the abdominal obliques seem to alter depending on the task and the
      presumable need for stability. The findings concerning the relative muscle
      activity and the ratios of the back muscles support the assumption that during
      these bridging exercises, all back muscles contribute in a similar way to control
      spine positions and movements in a healthy population.

PMID- 16987411
TI  - Cardioprotective aspirin users and their excess risk of upper gastrointestinal
      complications.
AB  - BACKGROUND: To balance the cardiovascular benefits from low-dose aspirin against
      the gastrointestinal harm caused, studies have considered the coronary heart
      disease risk for each individual but not their gastrointestinal risk profile. We
      characterized the gastrointestinal risk profile of low-dose aspirin users in real
      clinical practice, and estimated the excess risk of upper gastrointestinal
      complications attributable to aspirin among patients with different
      gastrointestinal risk profiles. METHODS: To characterize aspirin users in terms
      of major gastrointestinal risk factors (i.e., advanced age, male sex, prior ulcer
      history and use of non-steroidal anti-inflammatory drugs), we used The General
      Practice Research Database in the United Kingdom and the Base de Datos para la
      Investigacion Farmacoepidemiologica en Atencion Primaria in Spain. To estimate
      the baseline risk of upper gastrointestinal complications according to major
      gastrointestinal risk factors and the excess risk attributable to aspirin within
      levels of these factors, we used previously published meta-analyses on both
      absolute and relative risks of upper gastrointestinal complications. RESULTS:
      Over 60% of aspirin users are above 60 years of age, 4 to 6% have a recent
      history of peptic ulcers and over 13% use other non-steroidal anti-inflammatory
      drugs. The estimated average excess risk of upper gastrointestinal complications
      attributable to aspirin is around 5 extra cases per 1,000 aspirin users per year.
      However, the excess risk varies in parallel to the underlying gastrointestinal
      risk and might be above 10 extra cases per 1,000 person-years in over 10% of
      aspirin users. CONCLUSION: In addition to the cardiovascular risk, the underlying
      gastrointestinal risk factors have to be considered when balancing harms and
      benefits of aspirin use for an individual patient. The gastrointestinal harms may
      offset the cardiovascular benefits in certain groups of patients where the
      gastrointestinal risk is high and the cardiovascular risk is low.

PMID- 16987412
TI  - Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via
      IKK/NF-kappaB signaling.
AB  - BACKGROUND: Brain inflammation has been recognized as a complex phenomenon with
      numerous related aspects. In addition to the very well-described
      neurodegenerative effect of inflammation, several studies suggest that
      inflammatory signals exert a potentially positive influence on neural stem cell
      proliferation, migration and differentiation. Tumor necrosis factor alpha (TNF
      alpha) is one of the best-characterized mediators of inflammation. To date,
      conclusions about the action of TNF on neural stem or progenitor cells (NSCs,
      NPCs) have been conflicting. TNF seems to activate NSC proliferation and to
      inhibit their differentiation into NPCs. The purpose of the present study was to
      analyze the molecular signal transduction mechanisms induced by TNF and resulting
      in NSC proliferation. RESULTS: Here we describe for the first time the TNF
      mediated signal transduction cascade in neural stem cells (NSCs) that results in
      increased proliferation. Moreover, we demonstrate IKK-alpha/beta-dependent
      proliferation and markedly up-regulated cyclin D1 expression after TNF treatment.
      The significant increase in proliferation in TNF-treated cells was indicated by
      increased neurosphere volume, increased bromodeoxyuridin (BrdU) incorporation and
      a higher total cell number. Furthermore, TNF strongly activated nuclear factor
      kappa B (NF-kappaB) as measured by reporter gene assays and by an activity
      specific antibody. Proliferation of control and TNF-treated NSCs was strongly
      inhibited by expression of the NF-kappaB super-repressor IkappaB-AA1.
      Pharmacological blockade of IkappaB ubiquitin ligase activity led to comparable
      decreases in NF-kappaB activity and proliferation. In addition, IKK-beta gene
      product knock-down via siRNA led to diminished NF-kappaB activity, attenuated
      cyclin D1 expression and finally decreased proliferation. In contrast, TGFbeta
      activated kinase 1 (TAK-1) is partially dispensable for TNF-mediated and
      endogenous proliferation. Understanding stem cell proliferation is crucial for
      future regenerative and anti-tumor medicine. CONCLUSION: TNF-mediated activation
      of IKK-beta resulted in activation of NF-kappaB and was followed by up-regulation
      of the bona-fide target gene cyclin D1. Activation of the canonical NF-kappaB
      pathway resulted in strongly increased proliferation of NSCs.

PMID- 16987413
TI  - A phyloclimatic study of Cyclamen.
AB  - BACKGROUND: The impact of global climate change on plant distribution, speciation
      and extinction is of current concern. Examining species climatic preferences via
      bioclimatic niche modelling is a key tool to study this impact. There is an
      established link between bioclimatic niche models and phylogenetic
      diversification. A next step is to examine future distribution predictions from a
      phylogenetic perspective. We present such a study using Cyclamen (Myrsinaceae), a
      group which demonstrates morphological and phenological adaptations to its
      seasonal Mediterranean-type climate. How will the predicted climate change affect
      future distribution of this popular genus of garden plants? RESULTS: We
      demonstrate phylogenetic structure for some climatic characteristics, and show
      that most Cyclamen have distinct climatic niches, with the exception of several
      wide-ranging, geographically expansive, species. We reconstruct climate
      preferences for hypothetical ancestral Cyclamen. The ancestral Cyclamen lineage
      has a preference for the seasonal Mediterranean climate characteristic of dry
      summers and wet winters. Future bioclimatic niches, based on BIOCLIM and Maxent
      models, are examined with reference to a future climate scenario for the 2050s.
      Over the next 50 years we predict a northward shift in the area of climatic
      suitability, with many areas of current distribution becoming climatically
      unsuitable. The area of climatic suitability for every Cyclamen species is
      predicted to decrease. For many species, there may be no areas with a suitable
      climate regardless of dispersal ability, these species are considered to be at
      high risk of extinction. This risk is examined from a phylogenetic perspective.
      CONCLUSION: Examining bioclimatic niches from a phylogenetic perspective permits
      novel interpretations of these models. In particular, reconstruction of ancestral
      niches can provide testable hypothesis about the historical development of
      lineages. In the future we can expect a northwards shift in climatic suitability
      for the genus Cyclamen. If this proves to be the case then dispersal is the best
      chance of survival, which seems highly unlikely for ant-dispersed Cyclamen. Human
      assisted establishment of Cyclamen species well outside their native ranges
      offers hope and could provide the only means of dispersal to potentially suitable
      future environments. Even without human intervention the phylogenetic perspective
      demonstrates that major lineages could survive climate change even if many
      species are lost.

PMID- 16987414
TI  - Cardioprotective effect of the Hibiscus rosa sinensis flowers in an oxidative
      stress model of myocardial ischemic reperfusion injury in rat.
AB  - BACKGROUND: The present study investigates the cardioprotective effects of
      Hibiscus rosa sinensis in myocardial ischemic reperfusion injury, particularly in
      terms of its antioxidant effects. METHODS: The medicinal values of the flowers of
      Hibiscus rosa sinensis (Chinese rose) have been mentioned in ancient literature
      as useful in disorders of the heart. Dried pulverized flower of Hibiscus rosa
      sinensis was administered orally to Wistar albino rats (150-200 gms) in three
      different doses [125, 250 and 500 mg/kg in 2% carboxy methyl cellulose (CMC)], 6
      days per week for 4 weeks. Thereafter, rats were sacrificed; either for the
      determination of baseline changes in cardiac endogenous antioxidants [superoxide
      dismutase, reduced glutathione and catalase] or the hearts were subjected to
      isoproterenol induced myocardial necrosis. RESULTS: There was significant
      increase in the baseline contents of thiobarbituric acid reactive substances
      (TBARS) [a measure of lipid per oxidation] with both doses of Hibiscus Rosa
      sinensis. In the 250 mg/kg treated group, there was significant increase in
      superoxide dismutase, reduced glutathione, and catalase levels but not in the 125
      and 500 mg/kg treated groups. Significant rise in myocardial thiobarbituric acid
      reactive substances and loss of superoxide dismutase, catalase and reduced
      glutathione (suggestive of increased oxidative stress) occurred in the vehicle
      treated hearts subjected to in vivo myocardial ischemic reperfusion injury.
      CONCLUSION: It may be concluded that flower of Hibiscus rosa sinensis (250 mg/kg)
      augments endogenous antioxidant compounds of rat heart and also prevents the
      myocardium from isoproterenol induced myocardial injury.

PMID- 16987415
TI  - Spatial analysis and mapping of malaria risk in Malawi using point-referenced
      prevalence of infection data.
AB  - BACKGROUND: Current malaria control initiatives aim at reducing malaria burden by
      half by the year 2010. Effective control requires evidence-based utilisation of
      resources. Characterizing spatial patterns of risk, through maps, is an important
      tool to guide control programmes. To this end an analysis was carried out to
      predict and map malaria risk in Malawi using empirical data with the aim of
      identifying areas where greatest effort should be focussed. METHODS: Point
      referenced prevalence of infection data for children aged 1-10 years were
      collected from published and grey literature and geo-referenced. The model-based
      geostatistical methods were applied to analyze and predict malaria risk in areas
      where data were not observed. Topographical and climatic covariates were added in
      the model for risk assessment and improved prediction. A Bayesian approach was
      used for model fitting and prediction. RESULTS: Bivariate models showed a
      significant association of malaria risk with elevation, annual maximum
      temperature, rainfall and potential evapotranspiration (PET). However in the
      prediction model, the spatial distribution of malaria risk was associated with
      elevation, and marginally with maximum temperature and PET. The resulting map
      broadly agreed with expert opinion about the variation of risk in the country,
      and further showed marked variation even at local level. High risk areas were in
      the low-lying lake shore regions, while low risk was along the highlands in the
      country. CONCLUSION: The map provided an initial description of the geographic
      variation of malaria risk in Malawi, and might help in the choice and design of
      interventions, which is crucial for reducing the burden of malaria in Malawi.

PMID- 16987416
TI  - Managerial attitude to the implementation of quality management systems in
      Lithuanian support treatment and nursing hospitals.
AB  - BACKGROUND: The regulations of the Quality Management System (QMS) implementation
      in health care organizations were approved by the Lithuanian Ministry of Health
      in 1998. Following the above regulations, general managers of health care
      organizations had to initiate the QMS implementation in hospitals. As no research
      on the QMS implementation has been carried out in Lithuanian support treatment
      and nursing hospitals since, the objective of this study is to assess its current
      stage from a managerial perspective. METHODS: A questionnaire survey of general
      managers of Lithuanian support treatment and nursing hospitals was carried out in
      the period of January through March 2005. Majority of the items included in the
      questionnaire were measured on a seven-point Likert scale. During the survey, a
      total of 72 questionnaires was distributed, out of which 58 filled-in ones were
      returned (response rate 80.6 per cent; standard sampling error 0.029 at 95 per
      cent level of confidence). RESULTS: Quality Management Systems were found
      operating in 39.7 per cent of support treatment and nursing hospitals and
      currently under implementation in 46.6 per cent of hospitals (13.7% still do not
      have it). The mean of the respondents' perceived QMS significance is 5.8 (on a
      seven-point scale). The most critical issues related to the QMS implementation
      include procedure development (5.5), lack of financial resources (5.4) and
      information (5.1), and development of work guidelines (4.6), while improved
      responsibility and power sharing (5.2), better service quality (5.1) and higher
      patient satisfaction (5.1) were perceived by the respondents as the key QMS
      benefits. The level of satisfaction with the QMS among the management of the
      surveyed hospitals is mediocre (3.6). However it was found to be higher among
      respondents who were more competent in quality management, were familiar with ISO
      9000 standards, and had higher numbers of employees trained in quality
      management. CONCLUSION: QMSs are perceived to be successfully running in one
      third of the Lithuanian support treatment and nursing hospitals. Its current
      implementation stage is dependent on the hospital size - the bigger the hospital
      the more success it meets in the QMS implementation. As to critical Quality
      Management (QM) issues, hospitals tend to encounter such major problems as lack
      of financial resources, information and training, as well as difficulties in
      procedure development. On the other hand, the key factors that assist to the
      success of the QMS implementation comprise managerial awareness of the QMS
      significance and the existence of employee training systems and audit groups in
      hospitals.

PMID- 16987417
TI  - End expiratory oxygen concentrations to predict central venous oxygen saturation:
      an observational pilot study.
AB  - BACKGROUND: A non-invasive surrogate measurement for central venous oxygen
      saturation (ScVO2) would be useful in the ED for assessing therapeutic
      interventions in critically ill patients. We hypothesized that either linear or
      nonlinear mathematical manipulation of the partial pressure of oxygen in breath
      at end expiration (EtO2) would accurately predict ScVO2. METHODS: Prospective
      observational study of a convenience sample of hemodialysis patients age > 17
      years with existing upper extremity central venous catheters were enrolled. Using
      a portable respiratory device, we collected both tidal breathing and end
      expiratory oxygen and carbon dioxide concentrations, volume and flow on each
      patient. Simultaneous ScVO2 measurements were obtained via blood samples
      collected from the hemodialysis catheter. Two models were used to predict ScVO2:
      1) Best-fit multivariate linear regression equation incorporating all respiratory
      variables; 2) MathCAD to model the decay curve of EtO2 versus expiratory volume
      using the least squares method to estimate the pO2 that would occur at <20% of
      total lung capacity. RESULTS: From 21 patients, the correlation between EtO2 and
      measured ScVO2 yielded R2 = 0.11. The best fit multivariate equation included
      EtCO2 and EtO2 and when solved for ScVO2, the equation yielded a mean absolute
      difference from the measured ScVO2 of 8 +/- 6% (range -18 to +17%). The predicted
      ScVO2 value was within 10% of the actual value for 57% of the patients. Modeling
      of the EtO2 curve did not accurately predict ScVO2 at any lung volume.
      CONCLUSION: We found no significant correlation between EtO2 and ScVO2. A linear
      equation incorporating EtCO2 and EtO2 had at best modest predictive accuracy for
      ScVO2.

PMID- 16987418
TI  - Does patient-physiotherapist agreement influence the outcome of low back pain? A
      prospective cohort study.
AB  - BACKGROUND: Recent research suggests that agreement between patients' and health
      professionals' perceptions may influence the outcome of various painful
      conditions. This issue has received little attention in the context of low back
      pain and physiotherapy interventions. The current study aimed at exploring the
      relationship between patient-physiotherapist agreement on baseline low back pain
      intensity and related functional limitations, and changes in patient outcomes
      four weeks later. METHODS: Seventy-eight patient-physiotherapist dyads were
      included in the study. At baseline, patients and physiotherapists completed a
      Numerical Rating Scale and the Roland-Morris Disability Questionnaire. Patients'
      perceptions were reassessed over the phone at follow-up. RESULTS: Using multiple
      regression, baseline level of patient-physiotherapist agreement on pain intensity
      was associated with both outcome measures at follow-up. Agreement on functional
      limitations had no impact on outcomes. CONCLUSION: The results of this study
      indicate that patient-physiotherapist agreement has some impacts on the short
      term outcomes of low back pain. Further research is needed to confirm these
      findings.

PMID- 16987419
TI  - Health-related quality of life in children with newly diagnosed cancer: a one
      year follow-up study.
AB  - BACKGROUND: Most studies on health-related quality of life (HRQOL) in children
      with cancer focussed on survivors. Only few studies have evaluated patients
      during ongoing oncological treatment. The aim of this study was a prospective
      assessment of HRQOL in children during the first year after diagnosis of cancer
      and an examination of demographic, medical, and parental predictors of HRQOL.
      METHODS: Fifty-two patients (mean age: 10.9 years) were assessed 6 weeks and 1
      year after diagnosis with the TNO-AZL Questionnaire for Children's Health-Related
      Quality of Life. Parents completed the Brief Symptom Inventory. RESULTS: Compared
      to a community sample, patients reported more physical complaints, reduced motor
      functioning and autonomy, and impaired positive emotional functioning 6 weeks
      after diagnosis. HRQOL significantly improved over the year. However, at 1 year,
      patients still showed reduced motor and emotional functioning. At 6 weeks,
      children with leukemia were most affected. At 1 year, patients with brain tumors
      complained about more physical symptoms than the other groups. Intensity of
      treatment and presence of medical complications mainly influenced HRQOL at 6
      weeks but less at 1 year. Parental psychopathology was associated with better
      cognitive functioning in the child. CONCLUSION: This prospective study found
      several domains of HRQOL to be compromised 6 weeks and 1 year after the diagnosis
      of cancer. Although HRQOL significantly increased over the year, there were
      important differences between diagnostic groups. The findings highlight the
      importance of repeated evaluation of HRQOL in children undergoing cancer
      treatment and consideration of specific differences between diagnostic groups.

PMID- 16987420
TI  - RB acute loss induces centrosome amplification and aneuploidy in murine primary
      fibroblasts.
AB  - BACKGROUND: Incorrect segregation of whole chromosomes or parts of chromosome
      leads to aneuploidy commonly observed in cancer. The correct centrosome
      duplication, assuring assembly of a bipolar mitotic spindle, is essential for
      chromosome segregation fidelity and preventing aneuploidy. Alteration of p53 and
      pRb functions by expression of HPV16-E6 and E7 oncoproteins has been associated
      with centrosome amplification. However, these last findings could be the result
      of targeting cellular proteins in addition to pRb by HPV16-E7 oncoprotein. To get
      a more detailed picture on the role of pRb in chromosomal instability and
      centrosome amplification, we analyzed the effects of the acute loss of
      retinoblastoma gene function in primary conditional Rb deficient mouse embryonic
      fibroblasts (MEFs). Moreover, since pRb is a transcriptional repressor,
      microarray analysis was done on pRb-competent and pRb-deficient MEFs to evaluate
      changes in expression of genes for centrosome homeostasis and for correct
      mitosis. RESULTS: Acute loss of pRb induces centrosome amplification and
      aneuploidy in the vast majority of cells analyzed. A time course analysis shows a
      decrease of cells with amplified centrosomes after 40 days from the adenoviral
      infection. At this time only 12% of cells still show amplified centrosomes.
      Interestingly, cells with pRb constitutive loss show a similar percentage of
      cells with amplified centrosomes. DNA-Chip analyses in MEFs wt (mock infected)
      and pRb depleted (Ad-Cre infected) cells reveal differential expression of genes
      controlling both centrosome duplication and mitotic progression. CONCLUSION: Our
      findings suggest a direct link between pRb status, centrosome amplification and
      chromosomal instability, and define specific mitotic genes as targets whose gene
      expression has to be altered to achieve or maintain aneuploidy.

PMID- 16987422
TI  - S1 gene sequence analysis of a nephropathogenic strain of avian infectious
      bronchitis virus in Egypt.
AB  - BACKGROUND: Infectious bronchitis is highly contagious and constitutes one of the
      most common and difficult poultry diseases to control. IBV is endemic in probably
      all countries that raise chickens. It exists as dozens of serotypes/genotypes.
      Only a few amino acid differences in the S1 protein of vaccine and challenge
      strains of IBV may result in poor protection. Tropism of IBV includes the
      respiratory tract tissues, proventriculus and caecal tonsils of the alimentary
      tract, the oviduct and the kidney. RESULTS: Infectious bronchitis virus (IBV)
      strain closely related to Massachusetts (Mass) serotype was isolated from broiler
      chickens suffering from severe renal and respiratory distresses. The isolate was
      serologically identified by Dot-ELISA and further characterized by RT-PCR then
      genotyped using S1 gene sequence analysis. Alignment of the S1 sequence of the
      isolate with 16 IBV strains revealed high homology to isolates related to Mass
      serotype. Inoculation with the strain reproduced the disease in experimental 1
      day-old chickens and resulted in 20% mortality, severe renal and moderate
      respiratory distresses. Marked histopathological changes in both kidney and
      trachea were observed in experimentally infected chickens. A protection study
      using the H120 live attenuated vaccine showed low protection rate in spite of
      high S1 sequence homology (97%). Protection based criteria were: virus re
      isolation attempts from trachea, tracheal and renal histopathology as well as IBV
      antigens detection by immunofluorescent antibody technique in kidney sections.
      CONCLUSION: Periodical evaluation of cross-protective capabilities of IBV
      vaccine(s) versus recently recovered field isolates should be performed to ensure
      optimum control of IBV.

PMID- 16987423
TI  - Adenoid Cystic Carcinoma of the lacrimal gland metastasising to the liver: report
      of a case.
AB  - BACKGROUND: Adenoid Cystic Carcinoma of the lacrimal gland is a rare tumour.
      Their aggressive behaviour, with a high-risk of local recurrence, and late
      distant spread of the tumour even after aggressive management has been reported.
      Metastasis to the liver is rare and when it occurs, it is usually part of
      widespread metastasis, and therefore surgical treatment is seldom considered.
      CASE PRESENTATION: We report a rare case of an isolated liver metastasis from a
      lacrimal gland adenoid cystic carcinoma 20 years after resection of the primary
      tumour. The patient presented with right upper quadrant pain radiating to the
      back and shortness of breath of 3 months duration. No local recurrence was
      detected during a 15 year follow-up with computerized tomography (CT) of the
      head. Abdominal CT scan demonstrated a solitary liver tumour with no other
      primary source, and the bone scan was normal. The patient was treated with an
      extended right hemihepatectomy. The histology revealed a predominantly cribriform
      tumour with focal areas of basaloid type metastatic lacrimal gland adenoid cystic
      carcinoma. CONCLUSION: This case illustrates the unpredictable behaviour of
      adenoid cystic carcinoma and the need for a life long follow up for these
      patients after treatment. The possibility of surgical resection for liver
      metastasis from adenoid cystic carcinoma should always be considered.

PMID- 16987421
TI  - A comprehensive analysis of the androgen receptor gene and risk of breast cancer:
      results from the National Cancer Institute Breast and Prostate Cancer Cohort
      Consortium (BPC3).
AB  - INTRODUCTION: Androgens have been hypothesised to influence risk of breast cancer
      through several possible mechanisms, including their conversion to estradiol or
      their binding to the oestrogen receptor and/or androgen receptor (AR) in the
      breast. Here, we report on the results of a large and comprehensive study of the
      association between genetic variation in the AR gene and risk of breast cancer in
      the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
      (BPC3). METHODS: The underlying genetic variation was determined by first
      sequencing the coding regions of the AR gene in a panel of 95 advanced breast
      cancer cases. Second, a dense set of markers from the public database was
      genotyped in a panel of 349 healthy women. The linkage disequilibrium
      relationships (blocks) across the gene were then identified, and haplotype
      tagging single nucleotide polymorphisms (htSNPs) were selected to capture the
      common genetic variation across the locus. The htSNPs were then genotyped in the
      nested breast cancer cases and controls from the Cancer Prevention Study II,
      European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort,
      Nurses' Health Study, and Women's Health Study cohorts (5,603 breast cancer cases
      and 7,480 controls). RESULTS: We found no association between any genetic
      variation (SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of
      breast cancer, nor were any statistical interactions with known breast cancer
      risk factors observed. CONCLUSION: Among postmenopausal Caucasian women, common
      variants of the AR gene are not associated with risk of breast cancer.

PMID- 16987424
TI  - A key role for STIM1 in store operated calcium channel activation in airway
      smooth muscle.
AB  - BACKGROUND: Control of cytosolic calcium plays a key role in airway myocyte
      function. Changes in intracellular Ca2+ stores can modulate contractile
      responses, modulate proliferation and regulate synthetic activity. Influx of Ca2+
      in non excitable smooth muscle is believed to be predominantly through store
      operated channels (SOC) or receptor operated channels (ROC). Whereas agonists can
      activate both SOC and ROC in a range of smooth muscle types, the specific trigger
      for SOC activation is depletion of the sarcoplasmic reticulum Ca2+ stores. The
      mechanism underlying SOC activation following depletion of intracellular Ca2+
      stores in smooth muscle has not been identified. METHODS: To investigate the
      roles of the STIM homologues in SOC activation in airway myocytes, specific siRNA
      sequences were utilised to target and selectively suppress both STIM1 and STIM2.
      Quantitative real time PCR was employed to assess the efficiency and the
      specificity of the siRNA mediated knockdown of mRNA. Activation of SOC was
      investigated by both whole cell patch clamp electrophysiology and a fluorescence
      based calcium assay. RESULTS: Transfection of 20 nM siRNA specific for STIM1 or 2
      resulted in robust decreases (>70%) of the relevant mRNA. siRNA targeted at STIM1
      resulted in a reduction of SOC associated Ca2+ influx in response to store
      depletion by cyclopiazonic acid (60%) or histamine but not bradykinin. siRNA to
      STIM2 had no effect on these responses. In addition STIM1 suppression resulted in
      a more or less complete abrogation of SOC associated inward currents assessed by
      whole cell patch clamp. CONCLUSION: Here we show that STIM1 acts as a key signal
      for SOC activation following intracellular Ca2+ store depletion or following
      agonist stimulation with histamine in human airway myocytes. These are the first
      data demonstrating a role for STIM1 in a physiologically relevant, non
      transformed endogenous expression cell model.

PMID- 16987425
TI  - Consumption of resistant starch decreases postprandial lipogenesis in white
      adipose tissue of the rat.
AB  - Chronic consumption of diets high in resistant starch (RS) leads to reduced fat
      cell size compared to diets high in digestible starch (DS) in rats and increases
      total and meal fat oxidation in humans. The aim of the present study was to
      examine the rate of lipogenesis in key lipogenic organs following a high RS or DS
      meal. Following an overnight fast, male Wistar rats ingested a meal with an RS
      content of 2% or 30% of total carbohydrate and were then administered an i.p
      bolus of 50 muCi 3H2O either immediately or 1 hour post-meal. One hour following
      tracer administration, rats were sacrificed, a blood sample collected, and the
      liver, white adipose tissue (WAT), and gastrocnemius muscle excised and frozen
      until assayed for total 3H-lipid and 3H-glycogen content. Plasma triglyceride and
      NEFA concentrations and 3H-glycogen content did not differ between groups. In all
      tissues, except the liver, there was a trend for the rate of lipogenesis to be
      higher in the DS group than the RS group which reached significance only in WAT
      at 1 h (p < 0.01). On a whole body level, this attenuation of fat deposition in
      WAT in response to a RS diet could be significant for the prevention of weight
      gain in the long-term.

PMID- 16987427
TI  - Epiphanies, velcro balls and McDonaldization: highlights from the 5th Meeting of
      the International Society for Behavioral Nutrition and Physical Activity.
AB  - This commentary provides an overview and selected highlights from the scientific
      program of the 5th Annual Meeting of the International Society for Behavioral
      Nutrition and Physical Activity.

PMID- 16987429
TI  - Oesophagitis dissecans superficialis complicating repeated rigid oesophagoscopy
      and dilatation.
AB  - Oesophagitis dissecans superficialis is an extremely rare and benign condition
      where the mucosal epithelium of the oesophagus sloughs off along the whole length
      of the oesophagus and is expelled as an oesophageal cast. This condition has been
      reported in association with various aetiological factors. We report a case of an
      oesophageal cast in a patient who underwent repeated oesophagoscopy and
      dilatation for a postcricoid web. We discuss the possible relationship between
      trauma to the upper oesophagus and the development of oesophagitis dissecans
      superficialis.

PMID- 16987426
TI  - Identification of a human peripheral blood monocyte subset that differentiates
      into osteoclasts.
AB  - Increased bone resorption mediated by osteoclasts causes various diseases such as
      osteoporosis and bone erosion in rheumatoid arthritis (RA). Osteoclasts are
      derived from the monocyte/macrophage lineage, but the precise origin remains
      unclear. In the present study, we show that the purified CD16- human peripheral
      blood monocyte subset, but not the CD16+ monocyte subset, differentiates into
      osteoclast by stimulation with receptor activator of NF-kappaB ligand (RANKL) in
      combination with macrophage colony-stimulating factor (M-CSF). Integrin-beta3
      mRNA and the integrin-alpha(v)beta3 heterodimer were only expressed on CD16-
      monocytes, when they were stimulated with RANKL + M-CSF. Downregulation of beta3
      subunit expression by small interfering RNA targeting beta3 abrogated
      osteoclastogenesis from the CD16- monocyte subset. In contrast, the CD16+
      monocyte subset expressed larger amounts of tumor necrosis factor alpha and IL-6
      than the CD16- subset, which was further enhanced by RANKL stimulation.
      Examination of RA synovial tissue showed accumulation of both CD16+ and CD16-
      macrophages. Our results suggest that peripheral blood monocytes consist of two
      functionally heterogeneous subsets with distinct responses to RANKL. Osteoclasts
      seem to originate from CD16- monocytes, and integrin beta3 is necessary for
      osteoclastogenesis. Blockade of accumulation and activation of CD16- monocytes
      could therefore be a beneficial approach as an anti-bone resorptive therapy,
      especially for RA.

PMID- 16987430
TI  - Modelling Southern Ocean ecosystems: krill, the food-web, and the impacts of
      harvesting.
AB  - The ecosystem approach to fisheries recognises the interdependence between
      harvested species and other ecosystem components. It aims to account for the
      propagation of the effects of harvesting through the food-web. The formulation
      and evaluation of ecosystem-based management strategies requires reliable models
      of ecosystem dynamics to predict these effects. The krill-based system in the
      Southern Ocean was the focus of some of the earliest models exploring such
      effects. It is also a suitable example for the development of models to support
      the ecosystem approach to fisheries because it has a relatively simple food-web
      structure and progress has been made in developing models of the key species and
      interactions, some of which has been motivated by the need to develop ecosystem
      based management. Antarctic krill, Euphausia superba, is the main target species
      for the fishery and the main prey of many top predators. It is therefore critical
      to capture the processes affecting the dynamics and distribution of krill in
      ecosystem dynamics models. These processes include environmental influences on
      recruitment and the spatially variable influence of advection. Models must also
      capture the interactions between krill and its consumers, which are mediated by
      the spatial structure of the environment. Various models have explored predator
      prey population dynamics with simplistic representations of these interactions,
      while others have focused on specific details of the interactions. There is now a
      pressing need to develop plausible and practical models of ecosystem dynamics
      that link processes occurring at these different scales. Many studies have
      highlighted uncertainties in our understanding of the system, which indicates
      future priorities in terms of both data collection and developing methods to
      evaluate the effects of these uncertainties on model predictions. We propose a
      modelling approach that focuses on harvested species and their monitored
      consumers and that evaluates model uncertainty by using alternative structures
      and functional forms in a Monte Carlo framework.

PMID- 16987432
TI  - Starter strain related effects on the biochemical and sensory properties of
      Cheddar cheese.
AB  - A detailed investigation was undertaken to determine the effects of four single
      starter strains, Lactococcus lactis subsp. lactis 303, Lc. lactis subsp. cremoris
      HP, Lc. lactis subsp. cremoris AM2, and Lactobacillus helveticus DPC4571 on the
      proteolytic, lipolytic and sensory characteristics of Cheddar cheese. Cheeses
      produced using the highly autolytic starters 4571 and AM2 positively impacted on
      flavour development, whereas cheeses produced from the poorly autolytic starters
      303 and HP developed off-flavours. Starter selection impacted significantly on
      the proteolytic and sensory characteristics of the resulting Cheddar cheeses. It
      appeared that the autolytic and/or lipolytic properties of starter strains also
      influenced lipolysis, however lipolysis appeared to be limited due to a possible
      lack of availability or access to suitable milk fat substrates over ripening. The
      impact of lipolysis on the sensory characteristics of Cheddar cheese was unclear,
      possibly due to minimal differences in the extent of lipolysis between the
      cheeses at the end of ripening. As anticipated seasonal milk supply influenced
      both proteolysis and lipolysis in Cheddar cheese. The contribution of non-starter
      lactic acid bacteria towards proteolysis and lipolysis over the first 8 months of
      Cheddar cheese ripening was negligible.

PMID- 16987431
TI  - A case of mistaken identity--reappraisal of the species of canid and felid
      hookworms (Ancylostoma) present in Australia and India.
AB  - This study serves to clarify the current status of canid and felid Ancylostoma
      species present in Australia. The morphological identification of A. ceylanicum
      from cats for the first time in Townsville, Australia, appears to be in error,
      together with the genetic markers provided for the species. Morphological and
      genetic data presented herein provide strong evidence that the hookworms from
      cats in Towsville are not A. ceylanicum as previously identified (i.e. the first
      report of this species in Australia), but are A. braziliense. Therefore the
      subsequent genetic markers established for A. ceylanicum in subsequent molecular
      studies based on these Townsville specimens should also be attributed to A.
      braziliense. Based on this information, a study of canine hookworm species
      present in northern India is also in error and it is apparent that the hookworms
      found in this region are those of A. ceylanicum. The distribution of A.
      braziliense and A. ceylanicum in the Americas and Asia Pacific region is
      discussed together with the importance of combining parasite morphology with
      genetic data for parasite diagnosis in epidemiological studies.

PMID- 16987433
TI  - Genetic variants of beta-lactoglobulin gene and its association with milk
      composition traits in riverine buffalo.
AB  - A study was carried out to determine genetic variants of beta-lactoglobulin gene
      and to explore associations between these and milk composition traits in riverine
      buffalo. Single strand conformation polymorphism was employed to detect the
      genetic variants of the gene. Two fragments of this gene i.e. 119 bp of exon I
      and 400 bp spanning exon IV and intron IV were included in the study. For 119 bp
      fragment, three alleles namely, A, B and C were observed in all the buffalo
      breeds whereas four alleles (A, B, C and D) were detected for 400 bp fragment.
      The frequency distribution of alleles was different in different breeds of
      buffaloes for both the fragments. For exon I fragment, the milk composition
      traits such as total SNF, protein, solid, fat and whey protein yield were found
      to be significantly (P<0.05) associated with genotypes in Murrah and Bhadawari
      buffalo whereas in Mehsana breed genotypes were significantly (P<0.05) co-related
      with total SNF, solid and fat yield. Genotypes of 400 bp fragment, only total fat
      yield in Mehsana buffalo was found to be significantly (P<0.05) associated with
      genotypes.

PMID- 16987434
TI  - Yak milk casein as a functional ingredient: preparation and identification of
      angiotensin-I-converting enzyme inhibitory peptides.
AB  - Yak milk casein derived from Qula, a traditional Tibetan acid curd cheese, was
      hydrolyzed by six commercially available proteases (Trypsin, Pepsin, Alcalase,
      Flavourzyme, Papain and Neutrase). These hydrolysates were assayed for their
      inhibitory activity of Angiotensin-I-converting enzyme (ACE). The hydrolysates
      obtained by Neutrase from Bacillus amyloliquefaciens showed the highest ACE
      inhibitory activity. The IC50 value of Neutrase-hydrolysate was 0.38 mg/ml. The
      hydrolysate obtained by Neutrase was further separated by consecutive ultra
      filtration with 10 kDa and then with 6 kDa molecular weight cut-offs into
      different permeated parts and fractionated by gel filtration chromatography with
      a Sephadex G-25 column. The active fraction was subjected to RP-HPLC, in which
      five peaks were purified and identified. Amino acid sequence analysis confirmed
      that the peptides and origins were as follows: YQKFPQY (alphas2-CN; f89-95),
      LPQNIPPL (beta-CN; f70-77), SKVLPVPQK (beta-CN; f168-176), LPYPYY (kappa-CN; f56
      61) and FLPYPYY (kappa-CN; f55-61). Their amino acid sequences matched well with
      those of known bioactive peptides from bovine casein. The results indicated that
      yak milk casein could be a resource to generate antihypertensive peptides and be
      used as multifunctional active ingredients for many value-added functional foods
      as well as a traditional food protein.

PMID- 16987435
TI  - Dietary deprivation of fermented foods causes a fall in innate immune response.
      Lactic acid bacteria can counteract the immunological effect of this deprivation.
AB  - Extrinsic factors such as maternal microbiota, bacterial load of the environment,
      diet and medication modulate the intestinal microbiota. Maturation and function
      of the immune system is influenced by established gut microbiota. In this work we
      describe the immunological effects of the dietary deprivation of fermented foods
      of healthy volunteers. Significant decreases in faecal lactobacillus and total
      aerobes counts and concentration of short chain fatty acids were observed
      following deprivation of fermented food of the normal diet. Moreover, a decrease
      in phagocytic activity in leukocytes was observed after two weeks of restricted
      diet. Therefore, the dietary deprivation of fermented foods could induce a
      decrease in innate immune response that might affect the capacity to respond
      against infections. The ingestion of a probiotic product containing the strains
      Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711 or a
      standard yogurt containing a conventional starter Lactobacillus delbrueckii sp.
      bulgaricus counteracted the fall in the immune response, although the probiotic
      product was more effective than the standard yogurt.

PMID- 16987436
TI  - Determination of bovine lactoferrin in lactoferrin-supplemented dairy products
      and raw milk by an automated latex assay.
AB  - Latex immune agglutination method with a multipurpose auto-analyser (the
      automated latex assay) was validated for determination of bovine lactoferrin
      (BLF) in various dairy products. Reproducibility-within-laboratory (intermediate
      precision) due to day for infant formula, UHT milk and yogurt supplemented with
      BLF at 50 mg/100 g for infant formula and UHT milk, and at 100 mg/100 g for
      yogurt were 1.62 to 3.10 mg/100 g. Reproducibility-within-laboratory due to
      analysis (morning, noon, and evening) for raw milk was 1.59 mg/100 g. Trueness,
      accuracy in determining known amounts added for BLF-supplemented dairy products
      was -4.7 to -2.0 mg/100 g. BLF concentration in raw milks was 20.3 to 21.8 mg/100
      g. Although interference by the matrixes took place in infant formula and raw
      milk, BLF assays were accurately carried out by 2000-fold dilution or standard
      addition method. Automated latex assay for BLF is simple, rapid, precise and
      accurate enough for a routine method in various dairy products containing BLF.

PMID- 16987437
TI  - GATA factors in vertebrate heart development and disease.
AB  - Vertebrate heart formation is dependent upon complex hierarchical gene regulatory
      networks, which effect both the specification and differentiation of
      cardiomyocytes and subsequently cardiac morphogenesis. GATA-4, -5 and -6 comprise
      an evolutionarily conserved subfamily of transcription factors, which are
      expressed within the precardiac mesoderm from early stages in its specification
      and continue to be expressed within the adult heart. We review here the
      functional roles of individual GATA transcription factors in cardiac development,
      normal homeostasis and disease. We also review the cellular mechanisms employed
      to regulate the expression and downstream targets of the different GATA factors.

PMID- 16987438
TI  - [Family interventions in schizophrenia. From theory to the real world in Portugal
      today].
AB  - In the field of pychoeducational interventions in schizophrenia, terminology is
      sometimes misleading and further efforts are needed to specify and operationalise
      terms such as psychoeducation or family intervention, especially wherever they
      are adapted, for example, for use in non-English speaking countries. On the other
      hand, in spite of growing evidence of their clinical effectiveness, family
      interventions for schizophrenia are still not routinely implemented in real life
      clinical settings. Furthermore, the current poverty of original literature or
      replication studies in Portugal in the field of family interventions is
      astonishing. Several high-quality review papers have been published in the last
      two decades, summarising or meta-analysing data concerning efficacy,
      effectiveness and efficiency of these family interventions worldwide, but mostly
      in Anglo-Saxon literature. These findings were indeed incorporated in several
      clinical guidelines, namely in the United Kingdom. But there seems to exist, in a
      considerable number of settings, a lack of will to implement scientific findings
      established for more than twenty years. In developed countries, this should be
      addressed as a true paradox.

PMID- 16987439
TI  - [Depression and treatment. Apoptosis, neuroplasticity and antidepressants].
AB  - Depression's neurobiology begins to be better understood. The last decade data
      considers neuroplasticity and stress as implicated factors on the pathophisiology
      of depression. Because antidepressants have a lag-time on their action it is
      possible that inhibition of neurotransmitters recaptation is not sufficient to
      explain long term changes. For that purpose, neurogenesis increase, nervous
      fibers sprouting, new synapses and stabilization of the old ones can be
      responsible for those changes. AMPc-MAPcinases-CREB-BDNF cellular cascade can
      play a significant role in the mechanisms of dendritic restructuration,
      hippocampal neurogenesis increase and nervous cells survival. The aim of this
      article is to discuss if apoptosis could play a key role as an ethiopathogenic
      factor on the patogenesis of depression. It was done a medline search for
      references with apoptosis, stress, neuroplasticity, depression and
      antidepressants key-words. It were found 101 original or review references about
      these subjects. Stress plays a key role in the etiopathogeny of depression. Its
      deletery effects on apoptosis and neuroplasticity can be changed by
      antidepressants. Neurogenesis' increase is necessary for their action. This
      increase is reached with chronic antidepressant treatment and not with other
      psychotropic drugs which means some pharmacological specificity of
      antidepressants. AMPc, CREB, BDNF and Bcl-2 can be considered as target genes in
      antidepressant synthesis. At the level of this neurotrophic factors apoptosis
      might be included in the neuroplastic model of depression and play a prominent
      role in etiopathogeny of depression. To confirm that, we need more research on
      the field to know which are the mechanisms that trigger apoptosis and its
      biological significance. In relation to the last one, we can say that is possible
      to be physiological apoptosis in deteriorated neurons death which cannot make
      strong connections and pathological apoptosis because of stress via, namely, HPA
      axis.

PMID- 16987440
TI  - [Comorbidity between hepatitis C and depression. Epidemiological and
      etiopathogenic aspects].
AB  - Neuropsychiatric symptoms are commonly associated with chronic hepatitis C virus
      infection (HCV). The aim of this review of the literature was to evaluate the
      prevalence of depression in patients with hepatitis C, as well as the proposed
      etiopathogenic models. A review of the literature was undertaken using the
      complete search strategy devised by the Cochrane Collaboration Review Group for
      Depression, Anxiety and Neurosis. All studies but one have shown that major
      depression in chronic HCV patients is significantly more common than in the
      general population (reported rates from 5.7% and 45%), being related with illness
      perception, functional disability, impaired quality of life, fatigue severity,
      and the presence of psychiatric comorbidity. The mechanism by which depression is
      related to Hepatitis C is still poorly understood. Authors address some possible
      mechanisms, such as the psychological impact of the knowledge that one has been
      infected with HCV and the direct effects of the virus itself on the Central
      Nervous System (eg. cytoquines).

PMID- 16987441
TI  - [Pressure ulcer management--Evidence-based interventions].
AB  - Despite improved awareness and quality of care among health care personnel,
      pressure ulcers prevalence remains high especially in the inpatient setting.
      Pressure ulcers are associated with increased morbidity and mortality, affecting
      the quality of life of patients and their caregivers, and significantly
      increasing direct and indirect healthcare costs. Early risk assessment for
      developing a pressure ulcer is essential to decide on the appropriate preventive
      measures and for initiation of a tailored therapeutic approach. Interventions
      include strategies to reduce extrinsic and intrinsic risk factors associated with
      tissue ischemia, optimization of patient's nutritional status, and local wound
      care. This revision intends to review current evidence-based therapeutic
      interventions in pressure ulcer care, and support implementation of management
      protocols in an inpatient ward.

PMID- 16987442
TI  - [Ticks associated to infectious pathologies in Portugal].
AB  - Ticks are hematophagos arthropods that parasitize terrestrial vertebrates. They
      are world wide, living in almost all terrestrial regions. Although mainly
      associated to animals, there are several tick species that bite humans and
      transmit tick-borne agents causing important infectious disease. In this paper
      the authors revise the most outstanding aspects of those arthropods as vectors of
      infectious pathogens in Portugal, focusing biologic, ecologic and epidemiologic
      features with Public Health interest.

PMID- 16987443
TI  - [Vulnerability and National Health Service].
AB  - Safegarding health has been an objective of every learned civilization, ancient
      and modern. In modern times, at least in the western world, the increase in
      longevity associated with social isolation has created further vu1nerability for
      the older individua1. Today, healthcare is a social burden of extremely high
      cost. Among us this service is provided by the National Health Service in
      accordance to the Constituicao da Republica Portuguesa (Constitution of the
      Portuguese Republic). Despite the constitutional guarantees of equa1ity in health
      there are obvious discrepancies in access to health care and the conditions that
      promote health such as education and wealth. In a poor country, even with limited
      resources, inequa1ity can be minimized via policies and practical measures
      founded in equa1ity and social responsibility, not only the principles of
      economic efficiency. Only in this way can we guarantee equa1 access to health and
      the distribution of available resources in accordance to health care necessities.
      Yet, the investment in high technology among us seems out of fase with the
      investment in the area concerning functional recovery from high morta1ity
      illness, such as stroke. In Portugal the problem is extremely bad. Life
      expectancy has been extended but qua1ity of life is still very low. Victims of
      the social order, the elderly live alone without family who can care for them; on
      the other hand, the lack of investment in recovery and social integration of
      individua1s with disabling scars, Turns the ends of their life's into a nightmare
      for themselves and their kin. It follows stating the necessity to analyse and
      define the criteria to be used when allocating resources in order to guarantee
      equality in health and relief from suffering and also to stop discrimination of
      vu1nerable populations in access to healthcare. Whatever the criteria, it must be
      pre-defined and its principles widely discussed, reiterating, only that longevity
      cannot be an acceptable criteria to value life. The article concludes drawing
      attention to the need to invest in health education, which is just as important
      as the fair distribution of precious health care resources in reducing harmful
      risks to the most vulnerable patients.

PMID- 16987445
TI  - [Appropriateness of hospitalization in a ward of internal medicine--using the
      Appropriateness Evaluation Protocol].
AB  - INTRODUCTION: The Appropriateness Evaluation Protocol (AEP) is an instrument to
      study the appropriate use of hospital beds based in objective criteria that
      classify a hospital admission as appropriate or inappropriate. OBJECT: Evaluate
      the appropriateness of hospital admissions and stays of the patients of our
      Internal Medicine Department using the concurrent version of AEP. METHOD:
      Transversal study where was evaluated the clinical record of the patients
      admitted to our Department of Internal Medicine on March 13th of 2003, excluding
      all these who were admitted the day of the study. We analyzed demographic and
      clinic parameters and the appropriateness of hospital admission and stay using
      the AEP. RESULTS: 22 patients fulfilled the inclusion criteria, 54.5% of male
      gender with a average age of 70.7 years. All the admissions were considered
      appropriate. The most common criteria was the need of intravenous therapy (100%),
      followed by the sudden lost of corporal mobility (12.3%). 27.3% of stays were
      considered inappropriate on the day of the study. The most common criteria of
      appropriateness was the need of intravenous therapy (93.7%). The most usual
      reason of inappropriate stay was the existence of planned discharge, but without
      the order written down in the clinical file (66.7%). CONCLUSIONS: The AEP allows
      an efficient evaluation of the appropriateness of the hospital admissions and
      stays in a Health Unit, being used for a better utilization of resources. In our
      department all admissions were justified and about a quarter of stays were
      considered inappropriate using the AEP.

PMID- 16987444
TI  - [Monitoring antibiotic consumption in the surgery and orthopaedics].
AB  - Monitoring antibiotic consumption is a valuable tool which has been increasingly
      used in the last years due to the current concern with the emergence of resistant
      microbial strains. The present study aimed at monitoring antibiotic consumption,
      evaluating the economic impact of hospital antibiotic prescription and assessing
      the relationship between the prescribed antibiotics and the indications for
      either prophylactic or therapeutic use. This was a longitudinal pilot-study for
      which data were collected in six privately managed public hospital units during
      the month of May 2004, with a resulting sample of 1,122 admitted patients. We
      observed a prescription incidence rate of 76.9%, corresponding to a total of
      1,154 dispensed antimicrobials, with a mean 71.2% of these antimicrobials being
      dispensed for the prophylaxis of surgical site infection (SSI). The mean cost of
      antibiotic courses was higher in cases of "suspected infection" (9.09 euro) or
      "confirmed infection" (8.74 euro) and lower in cases of "prophylaxis" (5.67
      euro), a finding which is explained by the shorter mean duration of the later.
      There was a considerable variation among the different hospital units regarding
      the type of antibiotic compound that was used for SSI prophylaxis, with a mean
      duration of antibiotic use of 2.61 days for this indication and about half of the
      prophylactic regimens lasting longer than 24 hours, a fact that suggests an
      insufficient observation of the current recommendations for antibiotic use in SSI
      prophylaxis. This finding indicates the need for an investigation on the actual
      existence of local recommendations for SSI prophylaxis in individual hospital
      units and also for the evaluation of the compliance of practicing surgeons with
      eventually existing recommendations.

PMID- 16987446
TI  - [Compulsory treatments in Macao: the first five years].
AB  - AIMS: To characterize compulsory treatments done in Macao in the five years after
      its implementation in 1999. METHOD: A descriptive and retrospective study was
      done consulting the clinical files of persons that did compulsory treatments in
      Macao in the five years after its implementation. RESULTS: The court always
      confirmed the requests for compulsory admissions, 24 patients were admitted and
      14 cases (58.3%) were men. The patients had a median age of 37.7 years (SD+/
      14.4). The most frequent motive of admission was danger and incapacity to consent
      treatment, in 16 cases (66.5%). The admission was urgent in 18 cases (75%) and
      the diagnosis of psychosis was made in 23 cases (95.8%). The length of
      hospitalization was 69 days (SD+/-47.9; minimum=2; Maximum=170). Compulsory
      ambulatory treatments were made in 6 cases (25%) and lasted 771 days (SD+/-380.5;
      minimum=76; Maximum=963). Annually, quotas of compulsory admissions varied
      between 0% and 2.4% and commitment rates between 0 and 1.7. CONCLUSIONS: Quotas
      and commitment rates for compulsory admissions appeared inferior compared, for
      example, to the ones of the European Union. Compulsory treatments were important,
      allowing to start therapeutics, that otherwise would be impossible, and to
      overcome dangerous situations. There is a need in Macao to clarify the population
      and relevant professional sectors about these treatments so that, whenever
      indicated, patients can benefit from them quickly and in better circumstances.

PMID- 16987447
TI  - [Diabetes in the elderly: our reality].
AB  - AIM: To evaluate the impact of the aging of our population in the growing of
      diabetes prevalence, among patients treated inward at our department. MATERIAL
      AND METHODS: The clinical files of 242 diabetics older than eighty years, treated
      between 1999 and 2002 were studied retrospectively. Demographic (sex, age, year
      of first contact), clinical (causes of admission, co-morbidities, duration of
      diabetes, previous hypoglycaemic treatment, duration of hospitalisation and
      evolution) and biochemical (glycaemia, HbA1c, lipaemia and C-peptide) data were
      recorded. RESULTS: A progressive rising in the number of aged patients was found
      during this period (seven in 1999 to 55 in 2002), with a large proportion of
      women (73%). The more frequent causes of in-hospital treatment were
      hyperglycaemia (20.6%) and feet ulcers (septic or necrotic) (16.5%). In nearly
      42% of the cohort an acute infection was found. Diabetes was unknown in 13% of
      cases and less than ten years of duration in 38%. In this cohort most of the
      patients (77%) were treated with oral hypoglycaemic drugs, mostly sulfonylureas.
      HbA1c mean value was 10.4 +/- 2.2%; C -peptide was measured in a subset of cases
      (n=79), suggesting deficient insulin secretion in 18% of them. The global mean
      duration of hospitalisation was eleven days. Nineteen patients (8%) died during
      the hospitalization. CONCLUSIONS: In this study, we concluded that diabetes in
      people older than 75 years, is being progressively more often diagnosed. The
      general metabolic control was bad (HbA1c mean value--10.4 +/- 2.2%), with a
      significant number of patients presenting a deficient C-peptide secretion,
      worsened by frequent coexisting infections. So, a strengthened clinical care,
      directed to a careful diagnosis and treatment, may effectively contribute to a
      better prognosis and quality of life of aged diabetic patients.

PMID- 16987448
TI  - [Primary progressive non-fluente aphasia].
AB  - When a subject shows changes in his/her ability to express himself/herself
      verbally or to understand the messages from the people he/she relates with, it is
      customary to say that such a person has a language disorder, nosologically
      classified in the field of aphasias. In this article, we show the case of a
      patient diagnosed with progressive aphasia, where such a diagnosis describes the
      data resulting from the neuropsychological assessment process. Finally, we
      provide a few reflections with regard to the case.

PMID- 16987449
TI  - [Portal pseudo-hypertension].
AB  - Authors present a case report of a 51 years old man, with a past history of
      peptic ulcer, arterial hypertension and dislipidemia. Three weeks before
      hospitalization he did a upper endoscopy that revealed a duodenal ulcer and
      oesophageal varices (grade II/III). During etiologic investigation, hepatic
      disease and portal hypertension were excluded. He had a goiter that invaded the
      anterior mediastinum. After thyroidectomy the oesophageal varices disappeared.

PMID- 16987450
TI  - [Role of atherogenic dyslipidemia in the development of metabolic syndrome].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to know if the diagnosis of metabolic
      syndrome (MS) as defined by International Diabetes Federation (IDF) criteria 2005
      identifies more subjects with atherogenic dyslipidemia and high cardiovascular
      risk than the National Cholesterol Education Program-Adult Treatment Panel III
      (NCEP-ATP-III) criteria. PATIENTS AND METHOD: Cross-sectional study in an adult
      population (20-70 years) of 344 subjects (158 males and 186 females), who visited
      an out-patient clinic in the metropolitan area of Valencia over a period of one
      year. Opportunistic search method was used. We studied: anthropometrics
      parameters, blood pressure, plasma lipids -non-high-density lipoprotein
      cholesterol (no-HDL-c), and total cholesterol:high-density lipoprotein
      cholesterol index (TC-HDL-c)-, glucose and insulin, and HOMA (Homeostasis Model
      Assessment) index. RESULTS: We have separated the subjects on the basis to the
      IDF or ATP-III criteria to define the MS. The MS define a group of subjects with
      important plasma lipids alterations and cardiovascular risk: increase of no-HDL
      c, of TC:HDL-c index and of apolipoprotein B. The TC:HDL-c index was > or = 6 in
      28.6% of the subjects with MS and only in 9.4% of the subjects without MS (p <
      0.0001) by IDF criteria and in 34.6% of the subjects with MS-ATP-III, and in 8.6%
      without MS-ATP-III (p < 0.0001). The apolipoprotein B > or = 1.2 g/l was observed
      in 44% of the subjects with MS and only in 26% without MS IDF criteria (p <
      0.0001), and only in 47.6% and 28.6%, respectively, by ATP-III criteria (p <
      0.0001). CONCLUSIONS: The MS defined by the IDF or ATP-III criteria equally
      identifies subjects with atherogenic dyslipidemia, with increase of no-HDL-c, of
      the TC: HDL-c index and of the apolipoprotein B and, for this reason, with high
      cardiovascular risk.

PMID- 16987451
TI  - [Prevalence and physical-mental comorbidity of chronic back and neck pain in
      Spain: results from the ESEMeD Study].
AB  - BACKGROUND AND OBJECTIVE: Chronic back pain (CBP) and chronic neck pain (CNP) are
      highly prevalent among the adult population. However, less is known about its
      comorbidity with other diseases and its impact on global functioning. The
      objectives of following study, that is part of the ESEMeD-Spain study, are to
      estimate CBP-CNP prevalence among Spanish population, its comorbidity with other
      physical and mental conditions, and its impact on global functioning. SUBJECTS
      AND METHOD: Cross-sectional household survey of a representative sample of the
      population of Spain 18 years or older. Sample size was 5,473 individuals. CBP-CNP
      and comorbid conditions were ascertained by self-report. Mental disorders were
      ascertained with the Composite International Diagnostic Interview and global
      functioning with the WHO Dissability Assessment Schedule. Response rate was
      78.6%. RESULTS: The one year prevalence of chronic CBP-CNP was 14.7%. A 65.7% of
      people with CBP-CNP reported at least one other comorbid condition, including
      other chronic pain conditions (49.4%), chronic physical conditions (40.7%), any
      mood disorders (7.9%), panic disorder (1.3%), posttraumatic stress disorder
      (1.5%) or generalized anxiety disorder (1.4%). Additionally, CBP-CNP negatively
      affected global functioning. However, comorbid conditions explained about one
      third of the association between CBP-CNP and global functioning. CONCLUSIONS: CBP
      CNP is highly prevalent and comorbid with other physical and mental conditions.
      Comorbidity negatively affects individuals global functioning.

PMID- 16987452
TI  - [Prevalence of dyslipidemia in outpatients of the Spanish health service: the
      HISPALIPID Study].
AB  - BACKGROUND AND OBJECTIVE: We intended to estimate the prevalence of dyslipidemia
      among patients attending outpatient clinics of the Spanish health service.
      PATIENTS AND METHOD: HISPALIPID is a multicenter, cross-sectional study performed
      in 33,913 patients (55.7% women) with a mean age of 54.6 +/- 18.3 years attended
      in outpatient clinics across 15 of the 17 autonomous communities of Spain. 1,461
      physicians (78.8% primary care physicians, and 21.2% specialists) participated in
      the study. Patients were considered having dyslipidemia if their doctor had
      established a previous diagnosis. RESULTS: A total of 8,256 patients (52.4%
      women, mean age 62.4 +/- 12.4 years) had been diagnosed with dyslipidemia,
      representing a global prevalence of 24.3% (CI95%: 23.8-24.8) (M: 26.2%; W:22.9%;
      P<0.001). The communities with the higher and lower prevalence were the Canary
      Islands (33.9%) and Cantabria (18.6%), respectively. About 87% dyslipemic
      patients presented an additional cardiovascular risk factor and 36.7% of
      dyslipemic patients had an associated cardiovascular disease. CONCLUSIONS: The
      prevalence of dyslipidemia is high in patients attending outpatient clinics of
      the Spanish health service (one out of four patients). In addition, these
      patients are at a high cardiovascular risk.

PMID- 16987453
TI  - [Present and future of telemedicine].

PMID- 16987454
TI  - [Professionality and professionalism: basis, contents, praxis and teaching].

PMID- 16987455
TI  - [Influence of genetic and environmental factors on lipid metabolism and
      cardiovascular risk associated with the apoE gene].
AB  - The apolipoprotein E (ApoE) plays an important role in lipid metabolism. This
      apoprotein presents three major isoforms (apoE2, apoE3 and apoE4) that modulate
      lipid levels. Carriers of the apoE4 allele have higher total and LDL-cholesterol
      plasma concentration and a greater coronary risk, particularly for myocardial
      infarction. Nevertheless, not all the people with this allele develop the
      disease, which suggests that other genetic or environmental factors are necessary
      for its total expression. In this review, we will analyze the importance of
      several polymorphisms in the apoE gene promoter region, as well as various
      environmental factors, including diet, in the association of this gene with lipid
      metabolism and cardiovascular risk.

PMID- 16987456
TI  - [Isoflavones in menopause women].
AB  - Phytoestrogens are composed derivatives of vegetables. The 2 main classes of
      interest to human health are lignans and isoflavones. Isoflavones exist in at
      least 15 different chemical forms and their effect on human health has been
      investigated to some extent (particularly, genistein and daidzein as high levels
      of these compounds are present in soybean). Isoflavones have similar structure to
      oestrogen and have the capacity to exert both oestrogenic and anti oestrogenic
      effects. They may block the effects of oestrogen in some tissues (e. g., the
      breast and endometrium), but act like an oestrogen in providing possible
      protection against bone loss and heart disease. Lignans are much more widespread
      in plant foods but investigation has been limited due to the complexity of
      measurement. The increasing interest in the use of the soybean and the
      phytoestrogens derived from the soybean is due to the results published on
      experimental animal actions, and in human case-control studies. There are many
      observational and epidemiologists studies that suggest the potential benefit of
      isoflavones on the menopause symptoms, the cardiovascular system, the
      osteoporosis and the estrogen dependent cancers, but many open questions exist.
      We must be very strict with certain observational studies by the possible
      influences of collateral factors to the isoflavones (exercise, type of diet,
      etc.), and attribute the beneficial effects may be due to own treatment.

PMID- 16987457
TI  - [Endogenous endophathalmitis caused by Streptococcus pneumoniae in an immune
      competent patient].

PMID- 16987458
TI  - [Geographical differences in metabolic syndrome prevalence. The case of Canary
      Islands (Spain)].

PMID- 16987459
TI  - [Hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus in an
      adult with Still disease].

PMID- 16987460
TI  - [Cerebral hemorrhage secondary to autonomic dysreflexia in a spinal cord injury].

PMID- 16987461
TI  - [Spontaneous cholecystocutaneous fistula in the ederly].

PMID- 16987462
TI  - [Expression of virulence factors by extraintestinal strains of Escherichia coli].

PMID- 16987463
TI  - [Infections due to HIV-2 and HTLV-1/2 in Spain].

PMID- 16987464
TI  - [Characterization of Escherichia coli isolates derived from phylogenetic groups A
      and B1 causing extraintestinal infection].
AB  - INTRODUCTION: Escherichia coli isolates from the non-pathogenic phylogenetic
      groups A and B1 rarely cause extraintestinal infections. The aim of this study
      was to analyze 37 E. coli isolates pertaining to phylogenetic groups A and B1 and
      compare them with 37 E. coli isolates from group B2 and 31 from group D, which
      caused the same infections. METHODS: Among 105 E. coli isolated from the urine of
      patients with cystitis and pyelonephritis and from the blood of patients with
      urinary-source and other-source bacteriemia, the E. coli phylogenetic groups, 15
      virulence-associated genes, 7 O-antigens and fluoroquinolone resistance were
      analyzed. RESULTS: E. coli from groups A and B1 showed fewer virulence
      determinants (median 3.5) than E. coli from group B2 (8.6, P < 0.01) or D (5.3, P
      < .001); however, a subgroup containing 3 isolates from group A and 5 from B1
      harbored 5 or more factors. E. coli from groups A/B1 were associated with
      resistance to fluoroquinolones (74%, P < .001), whereas E. coli from group B2
      were associated with susceptibility to this antibiotic (76%, P = .003). E. coli
      from groups A/B1 were isolated significantly more frequently in patients with
      pyelonephritis or sepsis and local or general factors favoring infection,
      association not observed in patients with cystitis. CONCLUSIONS: Even though most
      of the E. coli isolates from phylogenetic groups A and B1 presented a low
      virulence potential, they were able to cause extraintestinal infections,
      particularly in compromised patients.

PMID- 16987465
TI  - [Pharmacoeconomic analysis of a maintenance strategy with lopinavir/ritonavir
      monotherapy in HIV-infected patients].
AB  - AIMS: To conduct a cost-efficacy analysis of lopinavir/ritonavir (LPV/r)
      monotherapy as a maintenance regimen following induction of virological response
      with triple therapy including LPV/r. The pharmacoeconomic analysis was performed
      from the perspective of the Spanish public health system. METHODS: A cost
      efficacy analysis was performed in a phase IV-II, comparative, randomized,
      multicenter, open-label clinical trial evaluating the efficacy and safety of
      maintenance therapy with LPV/r monotherapy versus continuation of triple therapy
      in HIV-infected patients with a persistently undetectable viral load for 6
      months. For the pharmacoeconomic analysis, efficacy was defined as the proportion
      of patients with plasma HIV RNA concentrations < 50 copies/mL at 48 weeks from
      the start of the study. An intent-to-treat analysis was performed. Only direct
      costs were considered. Cost, efficacy and the cost-efficacy ratio were calculated
      for each treatment option. RESULTS: The cost-efficacy ratio of LPV/r maintenance
      monotherapy was 5186 euros per unit of achieved effect (patient with plasma HIV
      RNA concentrations < 50 copies/mL at 48 weeks), whereas maintenance with triple
      therapy had a cost-efficacy ratio of 8688 euros per unit of achieved effect.
      CONCLUSION: The option of LPV/r monotherapy as maintenance therapy in HIV
      infected patients following induction of virological response with triple therapy
      including LPV/r might be a more efficient alternative than maintaining triple
      therapy, as evidenced by a more favorable cost-efficacy ratio.

PMID- 16987466
TI  - [Validation of the PCR-based universal heteroduplex generator assay for
      identification of rifampicin-resistant and multiresistant Mycobacterium
      tuberculosis in Lima, Peru].
AB  - OBJECTIVE: To validate the polymerase chain reaction-based universal heteroduplex
      generator (PCR UHG-Rif) assay for identifying rifampin-resistant and multidrug
      resistant (MDR, resistant to isoniazid and rifampin) Mycobacterium tuberculosis
      in patients with pulmonary tuberculosis from communities in Lima (Peru) with a
      high incidence of resistant tuberculosis. DESIGN: To compare the results of
      antituberculosis drug susceptibility testing in clinical samples performed by the
      proportion method with those obtained by the PCR UHG-Rif assay, with the aim of
      analyzing the diagnostic capability of PCR UHG-Rif. RESULTS: Concordance for the
      identification of antituberculosis drug susceptibility was 0.95 (kappa = 0.899; P
      < .05), with a sensitivity and specificity of 0.973 and 0.922 (P < .05),
      respectively. The positive predictive value was 0.939 (95% CI: 0.879-0.970) and
      the negative predictive value was 0.965 (95% CI: 0.902-0.988). Nevertheless, the
      probability for MDR prediction was 0.981 (P < .05). PCR UHG-Rif allows the
      detection of mixed populations; discordant results can be explained by the
      presence of point mutations, missense mutations and mutations outside the rpoB
      "hot" region associated with rifampin-resistance. CONCLUSIONS: The PCR UHG-Rif
      assay detects mutations in the rpoB gene with excellent sensitivity and
      specificity, and suitable predictive values when compared with the standard
      method for determining susceptibility to antituberculosis drugs. This test can be
      considered an excellent tool that can contribute to tuberculosis control by
      correctly identifying patients infected with resistant and MDR bacilli, leading
      to a reduction in the cases of tuberculosis and resistant tuberculosis.

PMID- 16987467
TI  - [Bordetella pertussis detection by real-time PCR, immunofluorescence and culture:
      prospective evaluation and molecular epidemiology].
AB  - INTRODUCTION: An increase in the incidence of pertussis has been observed in
      recent years. The aim of this study was to determine the usefulness of several
      procedures, including real-time PCR, for the laboratory diagnosis of pertussis,
      and to investigate clonal relationships among clinical isolates of Bordetella
      pertussis. METHODS: During the period of August 2002 to October 2003,
      nasopharyngeal swabs were collected from pediatric and adult patients with
      symptoms of pertussis, and contact cases. The samples were processed by culture,
      direct fluorescence assay (DFA), and real-time PCR. Most of the isolates were
      further characterized by pulsed-field gel electrophoresis (PFGE). RESULTS: Among
      121 clinical samples corresponding to 117 patients, B. pertussis was detected in
      17 samples by culture (14.1%), 30 samples (24.8%) by DFA and 41 samples (33.9%)
      by real-time PCR. Real-time PCR diagnosed 26 and 24 more cases than culture and
      DFA, respectively. Seventeen clinical isolates were available for PFGE analysis,
      14 collected during the study period and three in 1997, 2000 and 2001. PFGE
      identified 5 different genotypes, 2 of which included 8 (genotype C) and 6
      (genotype E) isolates. Two of the older isolates (1997 and 2001) were identified
      as genotype C. CONCLUSION: Real-time PCR applied to the diagnosis of pertussis
      provided more positive results than DFA and culture, but the true diagnostic
      value of these results should be clarified. Two bacterial clones were dominant,
      and one of them has circulated at least since 1997.

PMID- 16987468
TI  - [Compliance with a culture-based strategy to prevent perinatal Group B
      streptococcal infection in a third-level hospital].
AB  - Protocols for the prevention of group B streptococcal disease are being widely
      used with proven efficacy. The aim of this study was to assess compliance with a
      culture-based approach recommending universal culture screening at 35-37 weeks'
      gestation, established in our hospital. A retrospective cohort study was
      undertaken from January 2003 to January 2004. Compliance with the culture-based
      approach was considered to be good (92.1%) and only partially amenable to
      improvements. Effectively, there are inherent limitations to the protocol that
      can be resolved with the use of other strategies, such as tests for quick
      identification of genital carrier status.

PMID- 16987469
TI  - [Bupropion use for smoking cessation in HIV-infected patients receiving
      antiretroviral therapy].
AB  - Smoking is the most important modifiable cardiovascular risk factor. Bupropion
      administration is an effective method to achieve smoking cessation (SC), but the
      drug is metabolized by the cytochrome P450 enzyme system and this might cause
      interactions with antiretroviral drugs. We present a prospective study of
      bupropion SC therapy in HIV-positive patients under antiretroviral treatment. A
      total of 21 patients were studied; 38% of them stopped smoking for more than one
      year. No clinically significant drug interactions were found. Bupropion SC
      therapy was effective in HIV-positive patients and did not cause significant
      clinical interactions with antiretroviral drugs.

PMID- 16987470
TI  - Streptococcus pneumoniae virulence factors and their clinical impact: An update.
AB  - The morbidity and mortality rates associated with Streptococcus pneumoniae remain
      very high worldwide. The virulence of this bacterium is largely dependent on its
      polysaccharide capsule, which is quite heterogeneous and represents a serious
      obstacle for designing effective vaccines. However, it has been demonstrated that
      numerous protein virulence factors are involved in the pathogenesis of
      pneumococcal disease. An important related finding from experimental animal
      models is that non-capsulated strains of pneumococci are protective against
      capsulated ones. Hence, new vaccine designs are focused on the surface proteins
      (e. g., PspA and PspC) and on the cytolysin, pneumolysin. Moreover, several
      virulence factors have potential value for pneumococcal diagnosis by urinalysis.
      In this paper, we review the virulence factors involved in bacteria-host
      interactions, and the new developments in vaccines and diagnostic methods.

PMID- 16987471
TI  - [Treatment of viral hepatitis (II). Treatment of chronic hepatitis C].
AB  - Hepatitis C virus infection is the principal cause of chronic liver disease,
      cirrhosis and hepatocellular carcinoma in the Western World. Chronic hepatitis C
      is often silent, most of the times discovered only by routine serologic or
      biochemical testing and the interval between infection and the development of
      cirrhosis exceed 30 years. Interestingly the complications of chronic hepatitis C
      virus infection can be prevented by antiviral therapy. At present, the
      combination of pegylated interferon-alfa and ribavirina has become the standard
      treatment of chronic hepatitis C. The management of HCV infection in "special
      populations" (HIV coinfection and HCV therapy-experienced patient) has improved
      significantly over the past few years, through a better knowledge of the disease
      and the publication of several clinical trials performed in these patients. At
      presents, a number of new anti-HCV therapies are in development. Future drugs for
      HCV infection might make possible to eradicate HCV in future.

PMID- 16987472
TI  - [Distal and lateral subungueal onychomycosis in a 71-year-old woman].

PMID- 16987473
TI  - [Fever in a patient with a renal transplant].

PMID- 16987474
TI  - [Erythema nodosum and neurological alterations].

PMID- 16987475
TI  - [New case of autochthonous tick-borne tularemia].

PMID- 16987476
TI  - [Interference of hemolysis in serological immunoassays].

PMID- 16987477
TI  - [Bacteremia due to Acinetobacter ursingii].

PMID- 16987478
TI  - [Immune reconstitution in HIV-infected patients. A prospective analysis].

PMID- 16987479
TI  - [Adjunctive therapy in tuberculous meningitis and human immunodeficiency virus
      coinfection].

PMID- 16987480
TI  - [Antenatal exposure to corticosteroids for fetal lung maturation and its
      repercussion on weight, length and head circumference in the newborn infant].
AB  - BACKGROUND AND OBJECTIVE: To study the effects of antenatal corticosteroids
      treatment to promote fetal lung maturation, on fetal growth, depending on the
      number of the courses administered. PATIENTS AND METHOD: The study was based on
      data from the Spanish Collaborative Study of Congenital Malformations (ECEMC),
      analysing a sample of 29,557 singleton liveborn infants without congenital
      defects. An stratified analysis by gestational age was performed to compare the
      weight, length and head circumference at birth, in the exposed and unexposed
      infants to dexamethasone/betamethasone. To control confounding factors (year of
      birth, maternal age, gestational age, parity, maternal smoking and/or alcohol
      consumption, gestational diabetes, non-gestational diabetes and other maternal
      chronic diseases) we used a general linear model with random effects, being the
      randomised variable the place of birth. RESULTS: The exposure to more than one
      course of antenatal corticosteroids resulted in a significant reduction of birth
      weight, length and head circumference in singleton preterm infants. The birth
      weight decreased by 22% (p < 0.0001), the length 5% (p = 0.002) and the head
      circumference 6% (p = 0.0005). The treatment with only one course reduced also
      significantly the weight and length but not the head circumference. In addition,
      we observed a significant interaction between the treatment and gestational age
      at birth indicating that the effect of corticosteroids is stronger in the most
      premature babies. CONCLUSIONS: In this retrospective analysis, the antenatal
      exposure to corticosteroids to promote fetal maturation is associated with
      diminished weight, length and head circumference in the premature newborn infant.
      This negative effect was greater in those premature babies exposed to multiple
      courses.

PMID- 16987481
TI  - [Comparison of the SCORE function chart and the Framingham-REGICOR equation to
      estimate the cardiovascular risk in an urban population after 10 years of follow
      up].
AB  - BACKGROUND AND OBJECTIVE: Framingham-REGICOR and SCORE (Systematic Coronary Risk
      Evaluation) are 2 functions charts recommended to estimate the cardiovascular
      risk stratification in Spain. The aim of the present study was to validate to 10
      years the SCORE and REGICOR functions charts in 40 to 65 years old population.
      PATIENTS AND METHOD: 608 patients (56.7% female) with non evidence of
      cardiovascular disease were included in the present study. Patients were
      classified as high risk by REGICOR (> or = 10%) and by SCORE (> or = 5%)
      functions. RESULTS: The 90.6% of the population (551 subjects) did not
      experienced any cardiovascular events during the 10 years follow-up. The REGICOR
      function chart underestimated the coronary risk (4.9% vs 7.9%; p < 0.001),
      whereas the SCORE overestimated the cardiovascular risk of death (2.1% vs 1.5%; p
      < 0.001). In the SCORE function, the average risk of patients with events was
      6.1%, whereas the average risk of patients without events was 2.0% (p < 0.001)
      and 7.1% vs 4.8% (p < 0.001) in the REGICOR equation. The SCORE function obtained
      better validity criteria than REGICOR with a sensibility of 66.7% (95% confidence
      interval [CI], 66.2-67.2), especificity of 91.7%, (95% CI, 91.2-92.2) positive
      likelihood ratio of 8 (95% CI, 7.5-8.5), and eficacy of 91.1% (95% CI, 90.6
      91.6). These results were observed in both sexes: women -sensibility: 33.3% (95%
      CI, 32.4-34.2); especificity: 97.4% (95% CI, 96.5-98.3)- and men -sensibility:
      83.3% (95% CI, 82.7-83.9); especificity: 84.0% (95% CI, 83.4-84.6). CONCLUSIONS:
      The SCORE equation obtains better validity criteria than the REGICOR equation
      both in the total population and in males and females separately. These results
      make the SCORE function a powerful tool to estimate the cardiovascular risk.

PMID- 16987482
TI  - [Utility of dehydrated products in texture modified diets in elderly ambulatory
      patients].
AB  - BACKGROUND AND OBJECTIVE: The main objective of our work was to evaluate the
      influence in elderly ambulatory patients with dysphagia of a texture modified
      diet with dehydrated nutritional products on nutritional parameters and quality
      of life. PATIENTS AND METHOD: We enrolled 22 patients from the Nutrition
      Departament who had dysphagia and an age over 70 years. Patients received a
      texture modified diet supplemented with dehydrated nutritional products (Resource
      Mix Instant). RESULTS: A total of 22 patients were recruited with a gender
      distribution of 67% (n = 15) females, 33% (n = 7) males, and an average age of
      79.6 +/- 8.39 years. After treatment, we observed an improvement in fat free mass
      (39.8 +/- 3.14 kg vs 41.9 +/- 1.4 kg; p < 0.05), total proteins (6.1 [1.1] g/dl
      vs 6,8 [0.7] g/dl: p < 0.05), transferrin (145 [46] mg/dl vs. 198.5 [64] mg/dl; p
      < 0.05), albumin (2.7 [0.8] g/dl vs 3.3 [0.8] g/dl; p < 0.05) and lymphocytes
      (10(3U)/ml) (1367 [742] vs 1707 [898]: p < 0.05). Caloric, protein, fat and
      carbohydrates intakes increased in a significant way. In addition, the quality of
      life improved significantly (SF 36 score 95.7[13] vs 99.3[10]; p < 0.05).
      CONCLUSION: Incorporation of dehydrated nutritional products improved the dietary
      intake, nutritional status and quality of life in ambulatory elderly patients
      with dysphagia.

PMID- 16987483
TI  - [Fetal growth and corticosteroids].

PMID- 16987484
TI  - [Whipple's disease and central nervous system].

PMID- 16987486
TI  - [Use of digoxin in patients admitted because of heart failure].

PMID- 16987485
TI  - [Role of oxidative stress in respiratory diseases and its monitoring].
AB  - Together with inflammation and subsequent remodeling of airways, an imbalance
      between oxidative and anti-oxidative agents is generated during the development
      of numerous pulmonary diseases. This process seems to be involved in both the
      pathogenesis and chronification of asthma, chronic obstructive pulmonary disease
      (COPD), SOAS, interstitial lung diseases and cystic fibrosis. Reactive oxygen
      species including superoxide anion, hidroxyl radicals and hydrogen peroxide
      (H2O2) are synthetised as a response of inflammatory cells and are responsible of
      the oxidation of nucleic acids, proteins and membrane lipids, leading to cell
      damage and enhanced inflammation. Until recently, it was difficult to quantify
      the airway production of reactive oxidative species (ROS). In fact, it has been
      only in the last few years when it has been possible to determine indirectly the
      levels of ROS in expired air and in tissue of asthmatic patients. The analysis of
      exhaled air is a single, reproducible and non-invasive technique which is useful
      in the study of volatile and non-volatile gases generated in different
      conditions. The determination of exhaled nitric oxide and carbon monoxide (CO)
      has a great usefulness in the assessment of asthma. Nitric oxide seems to be
      closely related to the physiopathology of asthma and COPD. In fact, it is
      correlated with the levels of sputum eosinophils and with the response to the
      treatment with steroids. Yet a correlation with the degree of airflow obstruction
      and the seriousness of the process has not been found. Exhaled CO is another
      indirect marker of inflammation and it is increased in asthma, COPD, cystic
      fibrosis and bronchectases. Even though numerous studies have shown its
      usefulness as a marker of inflammation and in the response to corticosteroids,
      its clinical application has limitations. In particular, it is not a specific and
      exclusive marker of oxidative stress and its levels are highly influenced by
      tobacco smoke. On the other hand, the association between exhaled CO and FEV1 is
      not clear and no relationship has been proved so far with the improvement of
      pulmonary function after steroid therapy and with the decrease of maximum
      expiratory flow at relapses. In this Review, we describe the advances in the
      knowledge of oxidative stress as a decisive factor in the pathogenesis of
      prevalent pulmonary diseases, as well as the methods allowing its analysis and
      monitoring.

PMID- 16987487
TI  - [Lower digestive hemorrhage by masive mesenterial angiomatosis as an onset of
      Klippel-Trenaunay-Weber syndrome].

PMID- 16987488
TI  - [Bilateral neuralgic amyotrophy secondary to parvovirus B19 infection].

PMID- 16987489
TI  - [Alprazolam-induced tongue angioedema].

PMID- 16987490
TI  - Effect of piperazine (diethylenediamine) on the moulting, proteome expression and
      pyrophosphatase activity of Ascaris suum lung-stage larvae.
AB  - Piperazine (diethylenediamine) is an anthelmintic widely used against animal and
      bird ascariasis. In this study, we show that treatment with piperazine blocks
      Ascaris suum larval moulting and development processes and affects larval
      proteome expression profiles. A. suum lung-stage L3 (LL3) obtained from an
      infected rabbit's lungs were cultured in RPMI medium in the presence of
      increasing concentrations of piperazine sulfate (Pzes). Our results showed that
      Pzes potently inhibited moulting of A. suum LL3 in a dose-dependent manner and
      that moulting was completely blocked (100%) at 50mM concentrations. We then
      examined the changes in A. suum LL3 proteome expression patterns following Pzes
      exposure using two-dimensional (2D) electrophoresis. Pzes exposure inhibited
      expression of at least 16 major protein spots in unmoulted LL3 out of more than
      200 visible protein spots resolved on 2D gels prepared from moulted larvae (i.e.,
      lung-stage L4). Pzes exposure also inhibited expression of 13 immunogenic protein
      spots in unmoulted LL3. More importantly, Pzes exposure inhibited activity of a
      moulting-specific enzyme, inorganic pyrophosphatase of A. suum (AsPPase), by 26%.
      Expression of native AsPPase was also reduced following Pzes exposure as detected
      by immunoblotting and immunofluorescent staining. Transmission electron
      microscopy showed that Pzes interfered with growth and ecdysis of the cuticle and
      caused damage to gut tissues of the larvae. Our results suggest that A. suum LL3
      may become a suitable model to screening new-class anthelmintics with
      antimoulting functions and that A. suum LL3-Pzes may serve as a useful tool for
      identification of moulting-specific potential proteins in Ascaris roundworms.

PMID- 16987491
TI  - The use of aerial spraying to eliminate tsetse from the Okavango Delta of
      Botswana.
AB  - In Botswana, 16,000 km(2) of the Okavango Delta were aerial sprayed five times
      with deltamethrin, applied at 0.26-0.3g/ha, to control Glossina morsitans
      centralis Machado (Diptera: Glossinidae) over a period of approximately 8 weeks.
      The northern half of the Delta (7180 km(2)) was sprayed in June-September 2001
      and the southern half (8720 km(2)) in May-August 2002. A barrier (mean width
      approximately 10 km) of 12,000 deltamethrin-treated targets was deployed at the
      interface of these two blocks to prevent tsetse from invading from the southern
      to the northern block. Prior to spraying, the mean catches of tsetse from man fly
      rounds were 44.6 round/day in the northern block and 101 in the southern. Between
      September 2002 and November 2005, surveys ( approximately 820 daily fly-rounds
      and approximately 2050 trap-days) in the northern and southern blocks failed to
      detect tsetse. Simulations of tsetse populations suggest that while spraying
      operations can reduce tsetse populations to levels that are difficult to detect
      by standard survey techniques, such populations will recover to densities >100
      tsetse/km(2) after 1000 days, at which density there is a very high probability
      (>0.999) that the survey methods will catch at least one fly. Since none was
      caught, it is argued that tsetse have been eliminated from the Delta. The
      particular success of this operation in comparison to the 18 aerial spraying
      operations conducted in the Delta prior to 2001 is attributed to the application
      of an adequate dose of insecticide, the use of a GPS-based navigation system to
      ensure even application of insecticide, and the large size and spatial
      arrangement of the spray blocks coupled with the use of a barrier of targets
      which prevented tsetse from re-invading the northern sprayed block before the
      southern one was treated.

PMID- 16987492
TI  - N-terminal acylation of the SV40 nuclear localization signal peptide enhances its
      oligonucleotide binding and membrane translocation efficiencies.
AB  - Octanoyl and palmitoyl groups were coupled to the N-terminus of an analog of the
      SV40 nuclear localization signal peptide, SV126-133(Ser128), to study the effect
      of the fatty acid chain length on the complex formation with a single-stranded
      antisense oligodeoxynucleotide (ODN) and on the cellular uptake of the complex.
      The strongest binding affinity was observed for the palmitoylated peptide,
      indicating the better accessibility of the positively charged lysyl and arginyl
      side-chains to the phosphate groups due to the turn structures stabilized by the
      palmitoyl group. On increase of the peptide to ODN molar ratio (rM), gradual
      unstacking of the bases was observed, the maximal rate being reached at rM=10. At
      rM>10 restacking of the nucleotide bases was detected and the ODN was completely
      encapsulated in a liposome-like structure made up of palmitoylated peptides. Cell
      translocation experiments revealed a highly efficient cell transport of the ODN
      by palmitoylated SV40 peptide at rM>10.

PMID- 16987493
TI  - Expression of transforming K-Ras oncogene affects mitochondrial function and
      morphology in mouse fibroblasts.
AB  - K-ras transformed fibroblasts have been shown to have a stronger dependence from
      glycolysis, reduced oxidative phosphorylation ability and a fragility towards
      glucose depletion compared to their immortalized, normal counterparts. In this
      paper, using RNA profiling assays and metabolic perturbations, we report changes
      in expression of genes encoding mitochondrial proteins and alterations in
      mitochondrial morphology that correlate with mitochondrial functionality. In
      fact, unlike normal cells, transformed cells show reduced ATP content and
      inability to modify mitochondria morphology upon glucose depletion. Being
      reverted by GEF-DN expression, such morphological and functional changes are
      directly connected to Ras activation. Taken together with reported partial
      mitochondrial uncoupling and more sustained apoptosis of transformed cells, our
      results indicate that activation of the Ras pathway strikingly impacts on energy
      and signaling-related aspects of mitochondria functionality, that in turn may
      affect the terminal phenotype of transformed cells.

PMID- 16987495
TI  - Structure of antimicrobial peptides and lipid membranes probed by interface
      sensitive X-ray scattering.
AB  - The conformation and correlations of amphiphilic and antimicrobial peptides and
      the associated changes of lipid bilayers can be studied in oriented lipid
      membranes deposited on solid substrates. Here we review recent work on these
      systems, as studied by modern interface-sensitive X-ray and neutron scattering
      methods. Density profile, short range order of acyl chains and molecular
      conformations of peptides and lipids are probed in the fluid state of the
      bilayer. With an emphasis on technical aspects, we review recent work
      illustrating the potential of the methods and discuss its potential in the field.

PMID- 16987496
TI  - Attention control in middle childhood: relations to psychopathological symptoms
      and threat perception distortions.
AB  - The present study examined the construct of attention control, which is an
      important aspect of effortful control, in a sample of non-clinical children aged
      between 9 and 13 years. Results demonstrated that attention control was
      associated with a broad range of psychopathological complaints, including
      symptoms of anxiety, aggression, depression, and ADHD. As predicted, lower levels
      of attention control were accompanied by higher levels of these symptoms.
      Further, attention control was also negatively related to threat perception
      distortions, which indicates that children who display low levels of this
      regulative temperament factor are more prone to such cognitive biases. Third,
      when controlling for neuroticism, attention control remained significantly
      (negatively) associated with symptoms of anxiety, depression (child report only),
      and ADHD. The correlations between attention control and threat perception
      distortions largely disappeared when the influence of neuroticism was partialled
      out. Only the link between attention control and anxious interpretations of
      ambiguous vignettes survived this correction. Finally, no evidence was found for
      the hypothesised mediating role of cognitive distortions on the relation between
      temperament factors and psychopathological symptoms.

PMID- 16987497
TI  - Profiling human phosphodiesterase genes and splice isoforms.
AB  - A mere 21 human phosphodiesterase (PDE) genes are responsible for modulating
      cellular levels of cAMP and cGMP in response to stimuli. Considering the
      importance of cAMP and cGMP to disparate physiological functions including visual
      response, smooth muscle relaxation, platelet aggregation, immune response, and
      cardiac contractibility, perhaps the 200 or more splice isoforms of PDE genes
      also play a major functional role. We profiled the human PDEs across 25 tissue
      samples using splice sensitive oligonucleotide microarrays containing probes for
      exons and exon-exon junctions. Our results suggest that PDEs exhibit tissue
      specific differences in expression, as demonstrated by the high expression of
      PDE4B in skeletal muscle. At the splice variant level, the majority of PDE genes-
      notably 1A, 1C, 2A, 4C, 4D, 5A, 7A, 8A, 8B, 9A, 10A, and 11A--exhibited tissue
      specific splicing with potential functional implications for PDE biology. This
      work validates expression of many EST transcripts, and confirms and expands on
      published findings based on PCR and cloning, illuminating some of the complexity
      of cAMP and cGMP processing.

PMID- 16987498
TI  - EDEM1 regulates ER-associated degradation by accelerating de-mannosylation of
      folding-defective polypeptides and by inhibiting their covalent aggregation.
AB  - Proteins expressed in the endoplasmic reticulum (ER) are covalently modified by
      co-translational addition of pre-assembled core glycans (glucose(3)-mannose(9)-N
      acetylglucosamine(2)) to asparagines in Asn-X-Ser/Thr motifs. N-Glycan processing
      is essential for protein quality control in the ER. Cleavages and re-additions of
      the innermost glucose residue prolong folding attempts in the calnexin cycle.
      Progressive loss of mannoses is a symptom of long retention in the ER and elicits
      preparation of terminally misfolded polypeptides for dislocation into the cytosol
      and proteasome-mediated degradation. The ER stress-induced protein EDEM1
      regulates disposal of folding-defective glycoproteins and has been described as a
      mannose-binding lectin. Here we show that elevation of the intralumenal
      concentration of EDEM1 accelerates ER-associated degradation (ERAD) by
      accelerating de-mannosylation of terminally misfolded glycoproteins and by
      inhibiting formation of covalent aggregates upon release of terminally misfolded
      ERAD candidates from calnexin. Acceleration of Man(9) or Man(5)N-glycans
      dismantling upon overexpression was fully blocked by substitution in EDEM1 of one
      catalytic residue conserved amongst alpha1,2-mannosidases, thus suggesting that
      EDEM1 is an active mannosidase. This mutation did not affect the chaperone
      function of EDEM1.

PMID- 16987499
TI  - 15-deoxy-Delta12,14-prostaglandin J2 as a potential endogenous regulator of redox
      sensitive transcription factors.
AB  - 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) has been known to display
      multifaceted cellular functions, including anti-inflammatory and cytoprotective
      effects. However, depending on the concentrations and intracellular
      microenvironment, this cyclopentenone prostaglandin can exert opposite effects.
      Because of the alpha,beta-unsaturated carbonyl moiety present in its
      cyclopentenone ring structure, 15d-PGJ(2) can act as a Michael reaction acceptor
      and readily interacts with critical cellular nucleophiles, such as cysteine thiol
      groups in proteins. Many of the biological effects induced by 15d-PGJ(2) involve
      redox-transcription factors as the potential targets. Thus, 15d-PGJ(2) can
      modulate the transcriptional activities of nuclear factor-kappaB (NF-kappaB),
      activator protein-1 (AP-1), nuclear factor-erythroid 2p45 (NF-E2)-related factors
      (Nrf2), hypoxia inducible factor (HIF), etc. 15d-PGJ(2) is also well known as an
      endogenous ligand of peroxisome proliferator-activated receptor gamma
      (PPARgamma). However, the regulation of the aforementioned redox-sensitive
      transcription factors by 15d-PGJ(2) is not necessarily mediated via PPARgamma
      activation, but rather involves covalent modification or oxidation of their
      critical cysteine residues acting as a redox-sensor. This commentary describes
      the biological and physiological functions of 15d-PGJ(2) and underlying
      biochemical and molecular mechanisms with emphasis on the modulation of redox
      sensitive transcription factors and their regulators.

PMID- 16987500
TI  - A spontaneous tonic chloride conductance in solitary glutamatergic hippocampal
      neurons.
AB  - GABA-A receptors mediate both phasic synaptic inhibition and more recently
      appreciated tonic currents in the vertebrate central nervous system. We addressed
      discrepancies in the literature regarding the pharmacology of tonic currents by
      examining tonic currents in a controlled environment of dissociated, solitary
      glutamatergic neurons. We describe a novel tonically active, bicuculline
      sensitive chloride conductance that is insensitive to gabazine and to picrotoxin
      and thus not mediated by conventional GABA receptors. We exclude a significant
      contribution from small conductance calcium-gated potassium (SK) channels. We
      also pharmacologically exclude calcium-gated chloride channels, glycine receptors
      and the chloride current associated with glutamate transport. Finally, we
      demonstrate that, although small, this current modulates neuronal excitability.
      We speculate that this tonic current may provide a complementary mechanism for
      the regulation of neuronal excitability, particularly in regions with low ambient
      GABA concentrations. We conclude that this bicuculline-sensitive conductance
      needs to be accounted for in studies of GABA tonic currents, lest it be confused
      with currents associated with GABA overflow.

PMID- 16987502
TI  - BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant
      with IgA deposition in the kidney independent of LIGHT.
AB  - BAFF is a peripheral B cell survival factor and can mediate antibody (Ab) class
      switching. Over-expression of BAFF in mice results in B cell hyperplasia,
      elevated serum immunoglobulin (Ig), spontaneous germinal centre (GC) reactions
      and mild glomerulonephritis (GN). Here we show that, in addition to driving
      excessive levels of serum IgA, BAFF over-expression results in increased IgA
      levels within the intestinal lamina propria (LP) and deposition of IgA immune
      complexes in the renal glomerular mesangium. LIGHT has been previously shown to
      mediate a similar phenotype via signaling through the lymphotoxin-beta receptor
      (LTbetaR). We evaluated if LIGHT and BAFF cooperate in the etiology of a hyper
      IgA syndrome in BAFF-overexpressing transgenic (BAFF-Tg) mice. We find that LIGHT
      deficient BAFF-Tg mice exhibit similar levels of IgA in the serum, gut and kidney
      and develop nephritis to the same degree as LIGHT-sufficient BAFF-Tg mice.
      Therefore, in the context of BAFF over-expression, LIGHT is dispensable for the
      generation of a hyper-IgA syndrome accompanied by nephritis.

PMID- 16987501
TI  - Involvement of nitric oxide synthase and ROS-mediated activation of L-type
      voltage-gated Ca2+ channels in NMDA-induced DPYSL3 degradation.
AB  - Dihydropyrimidinase-like 3 (DPYSL3), a member of TUC (TOAD-64/Ulip/CRMP), is
      believed to play a role in neuronal differentiation, axonal outgrowth and
      possibly in neuronal regeneration. Recently, we have shown that in primary
      cortical neurons (PCN) NMDA and oxidative stress (H(2)O(2)) caused a calpain
      dependent cleavage of DPYSL3 (62 kDa) resulting in the appearance of a lower
      molecular weight form (60 kDa) of DPYSL3. Our preliminary results had shown that
      antioxidants significantly reduced NMDA-induced DPYSL3 degradation, indicating
      involvement of ROS in calpain activation. The aim of this study was to
      investigate the possible involvement of NOS in NMDA-induced DPYSL3 degradation.
      We found that NOS inhibitor (L-NAME) significantly prevented NMDA-induced ROS
      formation, as well as intracellular Ca(2+) increase [Ca(2+)](i), DPYSL3
      degradation and cell death. Further, exposure of PCN to NO donor (SNP) resulted
      in significant [Ca(2+)](i) increase, ROS generation and probable calpain-mediated
      DPYSL3 truncation. The NMDA- and oxidative stress (ROS)-induced DPYSL3 truncation
      was totally dependent on extracellular [Ca(2+)](i). While NMDA-induced DPYSL3
      truncation was blocked by both NMDA receptor antagonist (MK801) [Kowara, R.,
      Chen, Q., Milliken, M., Chakravarthy, B., 2005. Calpain-mediated degradation of
      dihydropyrimidinase-like 3 protein (DPYSL3) in response to NMDA and H(2)O(2)
      toxicity. J. Neurochem. 95 (2), 466-474] and L-VGCC (nimodipine) inhibitors,
      H(2)O(2)-induced increase in [Ca(2+)](i), ROS generation and DPYSL3 truncation
      was blocked only by nimodipine. These results indicate that changes in Ca(2+)
      homeostasis resulting from ROS-dependent activation of L-VGCC are sufficient to
      induce probable calpain-mediated DPYSL3 truncation and demonstrate for the first
      time the role of ROS in the mechanism leading to glutamate-induced calpain
      activation and DPYSL3 protein degradation. The probable calpain-mediated DPYSL3
      truncation may have significant impact on its interaction with actin and its
      assembly, and in turn on growth cone integrity.

PMID- 16987503
TI  - Tissue transglutaminase ELISA positivity in autoimmune disease independent of
      gluten-sensitive disease.
AB  - BACKGROUND: Our aim was to understand why some sera from patients with a broad
      spectrum of autoimmune diseases or non-autoimmune diseases involving enhanced
      apoptosis, cell lysis and/or putative secondary autoimmune processes show
      reactions in the tissue transglutaminase (TGc) ELISA used for diagnosis of gluten
      sensitive disease. METHODS: Sera were compared from groups of patients with
      autoimmune diseases, diseases involving organ specific enhanced cell death,
      celiac disease or dermatitis herpetiformis, diseases of non-autoimmune origin,
      and a group without known disease. IgA antibodies against TGc were detected using
      human antigen (produced recombinantly in bacterial or human cells) in different
      systems (non-commercial ELISA with buffers of differing NaCl concentrations, and
      anti-TGc sandwich ELISA). Anti-gliadin and anti-endomysium antibodies were also
      determined. RESULTS: Many sera from patients with autoimmune disorders gave a
      positive signal in the human TGc ELISAs. The signal appeared related to minor
      impurities in the recombinant human TGc used and to raised serum IgA antibody
      levels rather than to the occurrence of TGc specific antibodies in these
      patients. CONCLUSIONS: No association of anti-TGc Abs and autoimmune conditions
      independent of gluten-sensitive disease could be shown. Care should be taken to
      exclude copurification of chaperones, like heat shock protein 70, where preparing
      antigens for TGc ELISAs.

PMID- 16987504
TI  - The categorical structure of knowledge for famous people (and a novel application
      of Centre-Surround theory).
AB  - Knowledge of familiar people is essential to guide social interaction, yet there
      is uncertainty about whether semantic knowledge for people is stored in a
      categorical structure as for objects. Four priming experiments using hard-to
      perceive primes investigated whether occupation forms a category connecting
      famous persons in semantic memory. Primes were famous faces exposed for 17ms with
      masking, resulting in severely restricted awareness and thus precluding
      expectancy-based priming effects. Targets were consciously perceptible famous
      faces (Experiments 1-3), famous names (Experiment 3), or occupations (Experiment
      4) representing either the same or different occupation to the prime. Significant
      priming demonstrated the operation of automatic processes, including spreading
      activation, among persons sharing a common occupation; this supports the
      categorical view. The direction of priming (faster/slower responses to same
      occupation than different-occupation targets) was dependent on prime-target
      stimulus onset asynchrony (Experiments 1-3) and type of target (Experiment 4).
      This pattern of results is attributed to the Centre-Surround mechanism proposed
      by Carr and Dagenbach [Carr, T. H., & Dagenbach, D. (1990). Semantic priming and
      repetition priming from masked words: evidence for a centre-surround attentional
      mechanism in perceptual recognition. Journal of Experimental Psychology:
      Learning, Memory and Cognition, 16, 341-350]. These results support (a) the
      categorical structure of semantic knowledge for famous people and (b) the
      application of the Centre-Surround mechanism to the domain of person recognition.

PMID- 16987505
TI  - Efference copy and its limitations.
AB  - Efference copy, an internal brain signal informing the visual system of commands
      to move the eye, was the dominant explanation for visual space constancy for over
      a century. The explanation is not viable, however; the signal is to small, to
      slow, and too unreliable to support the perception of perfect constancy. Newer
      theories recognize that detailed image information does not survive refixation in
      any case. Efference copy is a viable explanation of static position perception
      and sensorimotor interaction, but the rich, stable visual world is an illusion.

PMID- 16987506
TI  - Examination of depth-weighted optical signals during cardiac optical mapping: a
      simulation study.
AB  - Optical mapping has become a powerful tool to explore complex cardiac
      propagation. Many experiments and studies claimed that the fluorescence obtained
      from tissue surface is the averaged response of the transmembrane potential upon
      probing depth rather than only on the surface. With the electrical propagation
      model and the photon transport model, the effects of depth-weighted optical
      signals are examined both during a normal excitation wave and a spiral wave. Our
      results indicate that depth-weighted optical signals may infer cardiac activation
      dynamics, such as the mode and the direction of the propagation, the spatial
      distribution of depolarization or repolarization.

PMID- 16987507
TI  - Single-trial evoked potential estimation using wavelets.
AB  - In this paper we present conventional and translation-invariant (TI) wavelet
      based approaches for single-trial evoked potential estimation based on
      intracortical recordings. We demonstrate that the wavelet-based approaches
      outperform several existing methods including the Wiener filter, least mean
      square (LMS), and recursive least squares (RLS), and that the TI wavelet-based
      estimates have higher SNR and lower RMSE than the conventional wavelet-based
      estimates. We also show that multichannel averaging significantly improves the
      evoked potential estimation, especially for the wavelet-based approaches. The
      excellent performances of the wavelet-based approaches for extracting evoked
      potentials are demonstrated via examples using simulated and experimental data.

PMID- 16987508
TI  - Regulation of wingless signaling by the CKI family in Drosophila limb
      development.
AB  - The Wingless (Wg)/Wnt signaling pathway regulates a myriad of developmental
      processes and its malfunction leads to human disorders including cancer. Recent
      studies suggest that casein kinase I (CKI) family members play pivotal roles in
      the Wg/Wnt pathway. However, genetic evidence for the involvement of CKI family
      members in physiological Wg/Wnt signaling events is lacking. In addition, there
      are conflicting reports regarding whether a given CKI family member functions as
      a positive or negative regulator of the pathway. Here we examine the roles of
      seven CKI family members in Wg signaling during Drosophila limb development. We
      find that increased CKIepsilon stimulates whereas dominant-negative or a null
      CKIepsilon mutation inhibits Wg signaling. In contrast, inactivation of CKIalpha
      by RNA interference (RNAi) leads to ectopic Wg signaling. Interestingly,
      hypomorphic CKIepsilon mutations synergize with CKIalpha RNAi to induce ectopic
      Wg signaling, revealing a negative role for CKIepsilon. Conversely, CKIalpha RNAi
      enhances the loss-of-Wg phenotypes caused by CKIepsilon null mutation, suggesting
      a positive role for CKIalpha. While none of the other five CKI isoforms can
      substitute for CKIalpha in its inhibitory role in the Wg pathway, several CKI
      isoforms including CG12147 exhibit a positive role based on overexpression.
      Moreover, loss of Gilgamesh (Gish)/CKIgamma attenuates Wg signaling activity.
      Finally, we provide evidence that several CKI isoforms including CKIalpha and
      Gish/CKIgamma can phosphorylate the Wg coreceptor Arrow (Arr), which may account,
      at least in part, for their positive roles in the Wg pathway.

PMID- 16987509
TI  - Parcas, a regulator of non-receptor tyrosine kinase signaling, acts during
      anterior-posterior patterning and somatic muscle development in Drosophila
      melanogaster.
AB  - We have isolated parcas (pcs) in a screen to identify novel regulators of muscle
      morphogenesis. Pcs is expressed in the ovary and oocyte during oogenesis and
      again in the embryo, specifically in the developing mesoderm, throughout muscle
      development. pcs is first required in the ovary during oogenesis for patterning
      and segmentation of the early Drosophila embryo due primarily to its role in the
      regulation of Oskar (Osk) levels. In addition to the general patterning defects
      observed in embryos lacking maternal contribution of pcs, these embryos show
      defects in Wingless (Wg) expression, causing losses of Wg-dependent cell types
      within the affected segment. pcs activity is required again later during
      embryogenesis in the developing mesoderm for muscle development. Loss and gain of
      function studies demonstrate that pcs is necessary at distinct times for muscle
      specification and morphogenesis. Pcs is predicted to be a novel regulator of non
      receptor tyrosine kinase (NRTK) signaling. We have identified one target of Pcs
      regulation, the Drosophila Tec kinase Btk29A. While Btk29A appears to be
      regulated by Pcs during its early role in patterning and segmentation, it does
      not appear to be a major target of Pcs regulation during muscle development. We
      propose that Pcs fulfils its distinct roles during development by the regulation
      of multiple NRTKs.

PMID- 16987510
TI  - A genome-wide analysis of biomineralization-related proteins in the sea urchin
      Strongylocentrotus purpuratus.
AB  - Biomineralization, the biologically controlled formation of mineral deposits, is
      of widespread importance in biology, medicine, and engineering. Mineralized
      structures are found in most metazoan phyla and often have supportive,
      protective, or feeding functions. Among deuterostomes, only echinoderms and
      vertebrates produce extensive biomineralized structures. Although skeletons
      appeared independently in these two groups, ancestors of the vertebrates and
      echinoderms may have utilized similar components of a shared genetic "toolkit" to
      carry out biomineralization. The present study had two goals. First, we sought to
      expand our understanding of the proteins involved in biomineralization in the sea
      urchin, a powerful model system for analyzing the basic cellular and molecular
      mechanisms that underlie this process. Second, we sought to shed light on the
      possible evolutionary relationships between biomineralization in echinoderms and
      vertebrates. We used several computational methods to survey the genome of the
      purple sea urchin Strongylocentrotus purpuratus for gene products involved in
      biomineralization. Our analysis has greatly expanded the collection of
      biomineralization-related proteins. We have found that these proteins are often
      members of small families encoded by genes that are clustered in the genome. Most
      of the proteins are sea urchin-specific; that is, they have no apparent
      homologues in other invertebrate deuterostomes or vertebrates. Similarly, many of
      the vertebrate proteins that mediate mineral deposition do not have counterparts
      in the S. purpuratus genome. Our findings therefore reveal substantial
      differences in the primary sequences of proteins that mediate biomineral
      formation in echinoderms and vertebrates, possibly reflecting loose constraints
      on the primary structures of the proteins involved. On the other hand, certain
      cellular and molecular processes associated with earlier events in skeletogenesis
      appear similar in echinoderms and vertebrates, leaving open the possibility of
      deeper evolutionary relationships.

PMID- 16987511
TI  - Lysosomal cathepsins in embryonic programmed cell death.
AB  - During limb development, expression of cathepsin D and B genes prefigure the
      pattern of interdigital apoptosis including the differences between the chick and
      the webbed digits of the duck. Expression of cathepsin L is associated with
      advanced stages of degeneration. Analysis of Gremlin-/- and Dkk-/- mouse mutants
      and local treatments with BMP proteins reveal that the expression of cathepsin B
      and D genes is regulated by BMP signaling, a pathway responsible for triggering
      cell death. Further cathepsin D protein is upregulated in the preapoptotic
      mesenchyme before being released into the cytosol, and overexpression of
      cathepsin D induces cell death in embryonic tissues by a mechanism including
      mitochondrial permeabilization and nuclear translocation of AIF. Combined
      inhibition of cathepsin and caspases suggests a redundancy in the apoptotic
      molecular machinery, providing evidence for compensatory activation mechanisms in
      the cathepsin pathway when caspases are blocked. It is concluded that lysosomal
      enzymes are functionally implicated in embryonic programmed cell death.

PMID- 16987512
TI  - Anti-arrhythmic and cardio-protective effects of furnidipine in a rat model: a
      dose response study.
AB  - Protective effects of acute oral or intravenous doses of furnidipine against
      ischemia and re-perfusion-induced arrhythmias and creatine kinase release were
      studied in a rat model for cardiac ischemia and re-perfusion. Transient cardiac
      ischemia was induced by occluding the left coronary descending artery of
      anaesthetized rats for 7 min, and re-perfusion period studied was 15 min. Pre
      treatment period for oral doses (1, 5 or 10 mg/kg) was 1 h, whereas that for the
      intravenous ones (1.25, 2.5, 5 or 10 microg/kg) was 10 min. After both routes of
      administration, significant protective effects of furnidipine on creatine kinase
      release were observed after the two lowest doses only. In contrast, its higher
      dosages were more effective in preventing re-perfusion-induced mortality,
      arrhythmias and hypotensive episodes, and for transiently lowering arterial blood
      pressure before initiation of ischemia. These observations suggest potential uses
      of furnidipine for preventing re-perfusion triggered lethal arrhythmias. Efforts
      to evaluate therapeutic potential of low dose furnidipine as a cardio-protective
      agent seem warrantable.

PMID- 16987513
TI  - Intermedin1-53 protects the heart against isoproterenol-induced ischemic injury
      in rats.
AB  - Intermedin is a novel member of the calcitonin/calcitonin gene-related peptide
      (CGRP) family peptide, which has vasodilatory and hypotensive actions identical
      to those of adrenomedullin and CGRP. Cleavage sites located between 2 basic amino
      acids at Arg93-Arg94 result in the production of prepro-intermedin95-147, namely
      intermedin1-53. The bioactive action of intermedin1-53 and its physiological
      significance are unclear. In this work, we aimed to explore the effects of
      intermedin1-53 on acute myocardial injury induced by isoproterenol. Myocardial
      ischemia injury in rats was induced by subcutaneous injection of a high dose of
      isoproterenol, and the therapeutic effect of intermedin1-53 was observed. Plasma
      lactate dehydrogenase activity, myocardial and plasma malondialdehyde content
      were higher in the isoproterenol group than that in controls. Isoproterenol
      treated rats showed lower maximal rate of increase and decrease of left-ventricle
      pressure development (+/-left-ventricle dp/dtmax) and higher left-ventricle end
      diastolic pressure (all P<0.01), which suggested severe heart failure and
      myocardial injury. Semi-quantitative RT-PCR analysis showed that the gene
      expression of calcitonin receptor-like receptor and receptor-activity-modifying
      protein (RAMP)1, RAMP2 and RAMP3 in ventricular myocardia were up-regulated by
      79% (P<0.01), 48% (P<0.01), 31% (P<0.05) and 130% (P<0.01), respectively,
      compared with controls. In myocardial sarcolemmal membranes, the maximum binding
      capacity for [125I]-intermedin1-53 was increased by 118% (P<0.01) in the
      isoproterenol group compared with controls. Rats treated with low dosage
      intermedin1-53 (5 nmol/kg/day, 2 days) showed 21% (P<0.05) higher myocardial cAMP
      content, 18% and 31% higher+left-ventricle dp/dtmax and -left-ventricle dp/dtmax
      respectively, 288% lower left-ventricle end-diastolic pressure (all P<0.01), and
      attenuated myocardial lactate dehydrogenase leakage and malondialdehyde formation
      (all P<0.01). Treatment with high dosage intermedin1-53 (20 nmol/kg/day, 2 days)
      gave better results than that with low dosage intermedin1-53. These results
      suggest that the intermedin receptor system was up-regulated in isoproterenol
      induced myocardial ischemic injury and intermedin1-53 might play a pivotal
      cardioprotective role in such injury.

PMID- 16987514
TI  - The protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3
      dephosphorylation and increases sarcoplasmic/endoplasmic reticulum calcium ATPase
      2 levels.
AB  - The ubiquitously expressed protein glycogen synthase kinase-3 (GSK3) is
      constitutively active, however its activity is markedly diminished following
      phosphorylation of Ser21 of GSK3alpha and Ser9 of GSK3beta. Although several
      kinases are known to phosphorylate Ser21/9 of GSK3, for example Akt, relatively
      much less is known about the mechanisms that cause the dephosphorylation of GSK3
      at Ser21/9. In the present study KCl-induced plasma membrane depolarization of SH
      SY5Y cells, which increases intracellular calcium concentrations caused a
      transient decrease in the phosphorylation of Akt at Thr308 and Ser473, and GSK3
      at Ser21/9. Overexpression of the selective protein phosphatase-1 inhibitor
      protein, inhibitor-2, increased basal GSK3 phosphorylation at Ser21/9 and
      significantly blocked the KCl-induced dephosphorylation of GSK3beta, but not
      GSK3alpha. The phosphorylation of Akt was not affected by the overexpression of
      inhibitor-2. GSK3 activity is known to affect sarcoplasmic/endoplasmic reticulum
      calcium ATPase 2 (SERCA2) levels. Overexpression of inhibitor-2 or treatment of
      cells with the GSK3 inhibitors lithium and SB216763 increased the levels of
      SERCA2. These results indicate that the protein phosphatase-1/inhibitor-2 complex
      differentially regulates GSK3 dephosphorylation induced by KCl and that GSK3
      activity regulates SERCA2 levels.

PMID- 16987515
TI  - A modified Plasmodium falciparum growth inhibition assay (GIA) to assess activity
      of plasma from malaria endemic areas.
AB  - Plasma samples from patients undergoing treatment in malaria endemic countries
      often contain anti-malaria drugs, that may overstate effects of specific
      antibodies in growth inhibition assays (GIA). We describe a modified assay that
      uses drug resistant P. falciparum parasites (W2) that circumvents the requirement
      for dialyzing samples that may likely contain drugs such as chloroquine and
      sulfadoxine/pyrimethamine (SP).

PMID- 16987516
TI  - A phagocytosis mutant of Entamoeba histolytica is less virulent due to deficient
      proteinase expression and release.
AB  - Cysteine proteinases are key virulence factors of Entamoeba histolytica that are
      released during the process of invasion. We used a chemical mutant of E.
      histolytica strain HM-1:IMSS, clone L6, which is deficient in virulence,
      phagocytosis, and cysteine proteinase activity to help define the mechanisms of
      cysteine proteinase release. All cysteine proteinase genes of wild type HM-1 were
      present in the L6 mutant genome, but three of the major expressed proteinases,
      ehcp1, ehcp2, and ehcp5 were both transcribed, translated, and released at lower
      levels in L6. We hypothesized that a central protein such as the calcium binding
      protein 1, EhCaBP1, which is required for both phagocytosis and exocytosis might
      be deficient in this mutant. We found that both mRNA and proteinase levels of
      EhCaBP1 were decreased in L6. These findings provide an important link between
      phagocytosis, passive release of multiple cysteine proteinases, and attenuated
      virulence of this E. histolytica mutant.

PMID- 16987517
TI  - Haemaphysalis longicornis: molecular characterization of a homologue of the
      macrophage migration inhibitory factor from the partially fed ticks.
AB  - The macrophage migration inhibitory factor (MIF) has been identified from some
      vertebrates and invertebrates. MIF is related to inflammation, tumor growth, and
      angiogenesis in vertebrates. Here, we report the molecular characterization of a
      homologue of MIF from partially fed Haemaphysalis longicornis. The sequence
      analysis of the H. longicornis MIF (HlMIF) indicated that its deduced amino acid
      sequence has an identity of 77% with the MIF of the tick Amblyomma americanum.
      Western blot analysis using the anti-His-HlMIF antibody showed that HlMIF was up
      regulated during blood feeding. Immunohistochemistry showed that the endogenous
      HlMIF in partially fed ticks was localized to the midgut and epidermal cells.
      Moreover, the functional assay revealed that the GST-HlMIF inhibited the
      migration of human monocytes. In conclusion, we consider that HlMIF may
      facilitate blood feeding by inhibiting host macrophage migration to the feeding
      lesion or may participate in the proliferation and differentiation of cells in
      the tick body.

PMID- 16987518
TI  - Disruption of parental-specific expression of imprinted genes in uniparental
      fetuses.
AB  - In mammals, imprinted genes show parental origin-dependent expression based on
      epigenetic modifications called genomic imprinting (GI), which are established
      independently during spermatogenesis or oogenesis. Due to GI, uniparental fetuses
      never develop to term. To determine whether such expression of imprinted genes is
      maintained in uniparental mouse fetuses, we analyzed the expression of 20
      paternally and 11 maternally expressed genes in androgenetic and parthenogenetic
      fetuses. Four genes of each type were expressed in both groups of fetuses.
      Furthermore, quantitative analysis showed that expression levels deviated from
      the presumed levels for some imprinted genes. These results suggest that
      mechanisms acting in trans between paternal and maternal alleles are involved in
      the appropriate expression of some imprinted genes.

PMID- 16987519
TI  - Peritoneal cavity phagocytes from the teleost sea bass express a glucocorticoid
      receptor (cloned and sequenced) involved in genomic modulation of the in vitro
      chemiluminescence response to zymosan.
AB  - To gain further insight into the role of cortisol in fish innate immune
      responses, we cloned and sequenced a 2592bp cDNA from sea bass (Dicentrarchus
      labrax) peritoneal leukocytes (PCLs) encoding a glucocorticoid receptor (DlGR1).
      The deduced aminoacid sequence displayed that DlGR1 belong to a multigenic family
      of steroid hormone receptors, and exhibited high homology (80%) to the Burton's
      mouth breeder (Haplochromis burtoni) HbGR1. The DlGR1 functional domains
      presented homologies with those of several vertebrate species. In situ
      hybridization assay revealed that DlGR1 was expressed in macrophages and
      neutrophils from the peritoneal cavity. Since in a previous paper, sea bass PCL
      chemiluminescence response (CL) has been related to increased respiratory burst
      of phagocytes stimulated with zymosan, PCLs, pre-incubated in vitro with cortisol
      at various concentrations, were assayed for their CL response. Dose-dependent
      cortisol inhibitory effects, and significant competitive activity of a low
      concentration of mifepristone (RU486), a glucocorticoid-receptor blocker,
      supported that cortisol-GR interaction was involved in modulating CL response via
      a genomic pathway. Results also indicated that cortisol could be effective
      through an additional not-genomic way, and showed that high doses of RU486
      exerted an inhibitory effect on PCL chemiluminescence activity.

PMID- 16987520
TI  - Effects of extracellular fiber architecture on cell membrane shear stress in a 3D
      fibrous matrix.
AB  - Interstitial fluid flow has been shown to affect the organization and behavior of
      cells in 3D environments in vivo and in vitro, yet the forces driving such
      responses are not clear. Due to the complex architecture of the extracellular
      matrix (ECM) and the difficulty of measuring fluid flow near cells embedded in
      it, the levels of shear stress experienced by cells in this environment are
      typically estimated using bulk-averaged matrix parameters such as hydraulic
      permeability. While this is useful for estimating average stresses, it cannot
      yield insight into how local matrix fiber architecture-which is cell-controlled
      in the immediate pericellular environment-affects the local stresses imposed on
      the cell surface. To address this, we used computational fluid dynamics to study
      flow through an idealized mesh constructed of a cubic lattice of fibers
      simulating a typical in vitro collagen gel. We found that, in such high porosity
      matrices, the fibers strongly affect the flow fields near the cell, with peak
      shear stresses up to five times higher than those predicted by the Brinkman
      equation. We also found that minor remodeling of the fibers near the cell surface
      had major effects on the shear stress profile on the cell. These findings
      demonstrate the importance of fiber architecture to the fluid forces on a cell
      embedded in a 3D matrix, and also show how small modifications in the local ECM
      can lead to large changes in the mechanical environment of the cell.

PMID- 16987521
TI  - Study of the surface character as responsible for controlling interfacial forces
      at membrane-feed interface.
AB  - The role of the interfacial forces was emphasized in interactive processes,
      involving membrane surface and penetrating molecules. The surface character
      controlling the dissolution process of some species (CO2, H2O, C3H6O2, C4H8O2,
      C5H10O2) was evaluated in relation to the supra-molecular chemistry of membranes
      based on 80PTMO/PA12. Infrared analyses combined with the estimation of the
      hydrophilic and hydrophobic domains of the membrane surface yielded useful
      information about the distribution, availability and accessibility of the polar
      moieties responsible for the penetrant sorption. At the interface, attractive
      Lewis acid/base interactions such as H-bonding directed the sorption of vapor
      species into the membranes, whereas quadrupolar CO2 participated in specific
      Lifshitz-van der Waals interactions with the modified polymers. In both the
      cases, the presence of additional polar moieties such as carbonyl, sulfonamide,
      and hydroxyl groups enhanced the affinity of the Pebax-based membranes for the
      penetrating species considered in this work. As a result, the quantification of
      the reactivity of a membrane surface for specific molecules may allow predictive
      models to be constructed and selective membranes to be designed.

PMID- 16987522
TI  - Detergency in spontaneously formed emulsions.
AB  - We report a microemulsion system with commercial nonionic surfactants, which
      produces kinetically stable o/w emulsions with sub-micron sized oil droplets,
      when added to water/brine. These emulsions have shown to be promising for fabric
      detergency. It is hypothesized that superior detergency could be due to (i) a low
      value of oil-emulsion interfacial tension (0.01-7 mN/m) even at a low (1 g/l)
      surfactant concentration, thus effecting rapid emulsification and solubilisation
      of oily matrix/film present in dirt and (ii) extremely tiny emulsion oil droplets
      (50-100 nm), which can have easy access to dirt entrapped in the inter-yarn
      voids. The aim of this work was to investigate the above factors in a model
      system (cellulose-coated glass slides with attached oil droplets) with a view to
      detergency. Further, an attempt was made to study changes in contact angles of
      oil droplets attached to cellulose-coated glass slides immersed in the emulsion
      system as a function of brine concentration. Correlations were drawn between
      equilibrium contact angle, interfacial tension and detergency at different brine
      concentrations through arguments of work of adhesion and showed an excellent
      match with detergency trends on commercial fabric test monitors. These
      correlations also provide insights into possible underlying mechanisms that
      account for detergency at each level of brine concentrations. An important
      consequence of the work is that superior detergency is achieved when the oil,
      present in the microemulsion, is physico-chemically similar to those oils which
      are to be removed from contaminated surfaces.

PMID- 16987523
TI  - A molecular-thermodynamic model for the interactions between globular proteins in
      aqueous solutions: applications to bovine serum albumin (BSA), lysozyme, alpha
      chymotrypsin, and immuno-gamma-globulins (IgG) solutions.
AB  - To investigate globular protein-protein and protein-salt interactions in
      electrolyte solutions, a potential of mean force including hard-core repulsion,
      van der Waals attraction and electric double layer repulsion is proposed in this
      work. Both van der Waals attraction and double-layer repulsion are represented
      using hard spheres with two-Yukawa tails. The explicit analytical solution of
      osmotic pressure is derived from the first-order mean spherical approximation.
      From the comparison between the calculated and experimental values of osmotic
      pressures for aqueous bovine serum albumin (BSA), lysozyme, alpha-chymotrypsin,
      and immuno-gamma-globulins (IgG) solutions, we found that the proposed model is
      adequate for the description of the interactions between proteins at low ionic
      strength and small self-association of protein molecules. At high ionic strength,
      the charge inversions of protein molecules should be taken into account.

PMID- 16987524
TI  - The role of juvenile hormone in competition and cooperation by burying beetles.
AB  - Few studies have addressed the physiological mechanisms that modulate aggression
      in insects. In some social insects, there is a correlation of JH and aggression
      in colony defense and in the establishment of dominance, but only a few studies
      demonstrate a causal relationship. Burying beetles aggressively defend a breeding
      resource, a carcass, and juvenile hormone (JH) hemolymph titers increase rapidly
      upon the discovery of a carcass. In this study, I show that treatment with the JH
      analog, methoprene, in the absence of a carcass increases the probability of
      injuries from aggressive interactions, but treatment to one member of a pair of
      competing Nicrophorus orbicollis females does not increase the probability that
      she will win control of the resource. In addition, higher JH levels are not
      associated with greater competitive ability in communally breeding Nicrophorus
      tomentosus females. Treatment of one female N. tomentosus does not increase her
      share of the communal brood. Methoprene seems to make a less competitive female
      more persistent and less willing to concede, which, although maintaining her
      share of reproduction, results in her exclusion from the brood chamber.

PMID- 16987525
TI  - Allosteric communication network in the tetrameric restriction endonuclease
      Bse634I.
AB  - Restriction endonuclease Bse634I is a homotetramer arranged as a dimer of two
      primary dimers. Bse634I displays its maximum catalytic efficiency upon binding of
      two copies of cognate DNA, one per each primary dimer. The catalytic activity of
      Bse634I on a single DNA copy is down-regulated due to the cross-talking
      interactions between the primary dimers. The mechanism of signal propagation
      between the individual active sites of Bse634I remains unclear. To identify
      communication pathways involved in the catalytic activity regulation of Bse634I
      tetramer we mutated a selected set of amino acid residues at the dimer-dimer
      interface and analysed the oligomeric state and catalytic properties of the
      mutant proteins. We demonstrate that alanine replacement of N262 and V263
      residues located in the loop at the tetramerisation interface did not inhibit
      tetramer assembly but dramatically altered the catalytic properties of Bse634I
      despite of the distal location from the active site. Kinetic analysis using
      cognate hairpin oligonucleotide and one and two-site plasmids as substrates
      allowed us to identify two types of communication signals propagated through the
      dimer-dimer interface in the Bse634I tetramer: the inhibitory, or "stopper" and
      the activating, or "sync" signal. We suggest that the interplay between the two
      signals determines the catalytic and regulatory properties of the Bse634I and
      mutant proteins.

PMID- 16987526
TI  - Folding on the chaperone: yield enhancement through loose binding.
AB  - A variety of small cageless chaperones have been discovered that can assist
      protein folding without the consumption of ATP. These include mini-chaperones
      (catalytically active fragments of larger chaperones), as well as small proteins
      such as alpha-casein and detergents acting as "artificial chaperones." These
      chaperones all possess exposed hydrophobic patches on their surface that act as
      recognition sites for misfolded proteins. They lack the complexity of chaperonins
      (that encapsulate proteins in their inner rings) and their study can offer
      insight into the minimal requirements for chaperone function. We use molecular
      dynamics simulations to investigate how a cageless chaperone, modeled as a sphere
      of tunable hydrophobicity, can assist folding of a substrate protein. We find
      that under steady-state (non-stress) conditions, cageless chaperones that bind to
      a single substrate protein increase folding yields by reducing the time the
      substrate spends in an aggregation-prone state in a dual manner: (a) by competing
      for aggregation-prone hydrophobic sites on the surface of a protein, hence
      reducing the time the protein spends unprotected in the bulk and (b) by
      accelerating folding rates of the protein. In both cases, the chaperone must bind
      to and hold the protein loosely enough to allow the protein to change its
      conformation and fold while bound. Loose binding may enable small cageless
      chaperones to help proteins fold and avoid aggregation under steady-state
      conditions, even at low concentrations, without the consumption of ATP.

PMID- 16987527
TI  - The DNA translocating ATPase of bacteriophage T4 packaging motor.
AB  - In double-stranded DNA bacteriophages the viral DNA is translocated into an empty
      prohead shell by a powerful ATP-driven motor assembled at the unique portal
      vertex. Terminases consisting of two to three packaging-related ATPase sites are
      central to the packaging mechanism. But the nature of the key translocating
      ATPase, stoichiometry of packaging motor, and basic mechanism of DNA
      encapsidation are poorly understood. A defined phage T4 packaging system
      consisting of only two components, proheads and large terminase protein (gp17; 70
      kDa), is constructed. Using the large expanded prohead, this system packages any
      linear double-stranded DNA, including the 171 kb T4 DNA. The small terminase
      protein, gp16 (18 kDa), is not only not required but also strongly inhibitory. An
      ATPase activity is stimulated when proheads, gp17, and DNA are actively engaged
      in the DNA packaging mode. No packaging ATPase was stimulated by the N-terminal
      gp17-ATPase mutants, K166G (Walker A), D255E (Walker B), E256Q (catalytic
      carboxylate), D255E-E256D and D255E-E256Q (Walker B and catalytic carboxylate),
      nor could these sponsor DNA encapsidation. Experiments with the two gp17 domains,
      N-terminal ATPase domain and C-terminal nuclease domain, suggest that terminase
      association with the prohead portal and communication between the domains are
      essential for ATPase stimulation. These data for the first time established an
      energetic linkage between packaging stimulation of N-terminal ATPase and DNA
      translocation. A core pathway for the assembly of functional DNA translocating
      motor is proposed. Since the catalytic motifs of the N-terminal ATPase are highly
      conserved among >200 large terminase sequences analyzed, these may represent
      common themes in phage and herpes viral DNA translocation.

PMID- 16987528
TI  - Structural determinants involved in the regulation of CXCL14/BRAK expression by
      the 26 S proteasome.
AB  - The chemokine CXCL14/BRAK participates in immune surveillance by recruiting
      dendritic cells. CXCL14 gene expression is altered in a number of cancers, but
      protein expression levels have not been investigated. Here we report that CXCL14
      protein can be expressed in primary epithelial cells; however, in several
      immortalized and cancer cell lines this protein is targeted for
      polyubiquitylation and proteasomal degradation. We determined the NMR structure
      of CXCL14 to identify motifs controlling its expression. CXCL14 adopts the
      canonical chemokine tertiary fold but contains a unique five amino acid insertion
      (41VSRYR45) relative to other CXC chemokines. Deletion or substitution of key
      residues within this insertion prevented proteasomal degradation. Furthermore, we
      defined a 15 amino acid fragment of CXCL14 that is sufficient to induce
      proteasomal degradation. This study elucidates a post-translational mechanism for
      the loss of CXCL14 in cancer and a novel mode of chemokine regulation.

PMID- 16987529
TI  - Trespassing on the tracks: a review of railway pedestrian safety research.
AB  - INTRODUCTION: Train-pedestrian collisions have been shown to be the leading cause
      of fatality in train-related accidents worldwide, yet there is remarkably little
      research in this area. METHOD: In this paper, the major types of railway
      transportation accident research are briefly highlighted to indicate the general
      context of research concerning train-pedestrian collisions, which are then
      reviewed. Themes emerging from the diverse research are identified, the various
      strategies that have been proposed for prevention of railway pedestrian accidents
      are discussed, and the empirical evidence for their efficacy examined in the
      light of the much more extensive literature on road pedestrian accidents.
      Finally, it is proposed that application of current theory in behavioral and
      cognitive psychology may usefully inform future research in transportation
      safety.

PMID- 16987530
TI  - Intramolecular interactions in aminoacyl cyclic-3',5'-nucleotides.
AB  - Polymerization of amino-acid acyl cyclic-3',5'-nucleotides is postulated to be
      the origin of RNA and associated protein in prebiotic molecular evolution. The
      enthalpy change in the intramolecular interaction between the nucleotide base and
      the amino-acid side chain determines the stability of the particular complex,
      resulting in a preferred association (or coding) of a base for a particular amino
      acid. The compounds studied were glycine acyl cyclic-3',5'-guanylate where the
      strong hydrogen bond between protonated glycine and guanine N7 gives an enthalpy
      change of -0.05 h. Similarly, hydrogen bonds in l-lysine acyl cyclic-3',5'
      adenylate give an enthalpy change of -0.06 h. Hydrophobic interactions in l
      phenylalanine acyl cyclic-3',5'-uridylate give an enthalpy change of -0.02 h and
      the corresponding value for l-proline acyl cyclic-3',5'-cytidylate is -0.01 h.
      These interactions were expected to be modified as the genetic code became a
      duplet and finally a triplet code. The interactions have been shown to be
      feasible from the overall enthalpy changes in the ZKE approximation at the MP2/6
      31G* level.

PMID- 16987531
TI  - Food webs robustness to biodiversity loss: the roles of connectance,
      expansibility and degree distribution.
AB  - We analyse the robustness of food webs against species loss by considering the
      influence of several structural factors of the networks, such as connectance,
      degree distribution and expansibility. The last concept refers to the absence of
      structural bottlenecks in the food web, whose removal separate the network into
      large isolate clusters. In theory networks with identical connectance can display
      different expansibility characteristics. Using the spectral scaling method we
      studied 17 food networks and classified them as good expansion (GE) and not-GE
      networks. The combination of GE properties and degree distribution of species
      permitted the classification of food webs into six different classes. These
      classes characterize the differences in robustness of food webs to species loss.
      While the webs having uniform degree distributions and displaying GE properties
      are the most robust to species loss, the presence of bottlenecks and skewed
      distribution of the number of links per species make food webs very vulnerable to
      primary removal of species.

PMID- 16987532
TI  - Review of solutions for 3D hydrodynamic modeling applied to aquaculture in South
      Pacific atoll lagoons.
AB  - A workshop organized in French Polynesia in November 2004 allowed reviewing the
      current methods to model the three-dimensional hydrodynamic circulation in semi
      enclosed atoll lagoons for aquaculture applications. Mollusk (e.g. pearl oyster,
      clam) aquaculture is a major source of income for South Pacific countries such as
      French Polynesia or Cook Islands. This aquaculture now requires a better
      understanding of circulation patterns to improve the spatial use of the lagoons,
      especially to define the best area to set larvae collectors. The pelagic larval
      duration of the relevant species (<20 days) and the size of the semi-closed
      lagoons (few hundreds of km2) drive the specifications of the model in terms of
      the spatial and temporal scale. It is considered that, in contrast with fish,
      mollusk larvae movements are limited and that their cycle occurs completely in
      the lagoon, without an oceanic stage. Atolls where aquaculture is productive are
      generally well-bounded, or semi-closed, without significant large and deep
      openings to the ocean. Nevertheless part of the lagoon circulation is driven by
      oceanic water inputs through the rim, ocean swells, tides and winds. Therefore,
      boundary conditions of the lagoon system are defined by the spatial structure of
      a very shallow rim (exposition and number of hoas), the deep ocean swell climate,
      tides and wind regimes. To obtain a realistic 3D numerical model of lagoon
      circulation with adequate forcing, it is thus necessary to connect in an
      interdisciplinary way a variety of methods (models, remote sensing and in situ
      data collection) to accurately represent the different components of the lagoon
      system and its specific boundary conditions. We review here the current methods
      and tools used to address these different components for a hypothetical atoll of
      the Tuamotu Archipelago (French Polynesia), representative of the semi-closed
      lagoons of the South Pacific Ocean. We hope this paper will serve as a guide for
      similar studies elsewhere and we provide guidelines in terms of costs for all the
      different stages involved.

PMID- 16987534
TI  - Attentional performance of (C57BL/6Jx129Sv)F2 mice in the five-choice serial
      reaction time task.
AB  - Impaired attention is evident in several neurological and psychiatric disorders.
      In the present study, attentional capabilities were measured in the operant five
      choice serial reaction time task (5-CSRTT) in male (C57BL/6Jx129Sv)F2 hybrid
      (B6129F2) mice. Main aims were to validate and standardize the test in these
      mice: to setup procedures, measure potential beneficial effects of sub-chronic
      nicotine in degraded versions of the 5-CSRTT (by decreasing stimulus duration,
      inducing white noise and making the stimuli unpredictable) and study disruptive
      effects of additional administration of the muscarinic antagonist scopolamine.
      During the baseline pre-nicotine sessions, the B6129F2 mice attained a very good
      performance in the test (95% accuracy). As stimulus duration was reduced from 2 s
      to 1 s, response accuracy of the mice decreased. Mice treated with nicotine (0.16
      mg/kg) attained significantly higher response accuracy and had a lower percentage
      of incorrect responses in comparison with the solvent-treated animals. No further
      beneficial effects of nicotine were found. Reduced response accuracy was also
      obtained when stimulus duration was reduced from 1 s to 0.5 s and when a variable
      intertrial interval was introduced. Noise interpolation between trials did not
      impair performance. Finally, scopolamine (0.16 mg/kg) disrupted attentional
      functioning. Although most studies have been performed in rats, these results add
      to the existing evidence that the 5-CSRTT can also be used to assess attentional
      performance in mice. This offers the opportunity to test transgenic and knockout
      mice with similar background as the B6129F2 as animal models of psychiatric and
      neurological diseases.

PMID- 16987536
TI  - Investigation on the different types of resonators in the thermoacoustic Stirling
      prime mover.
AB  - A new thermoacoustic Stirling prime mover consisting of a looped tube and
      different types of resonators respectively has been built. Experiments were
      focused on three axisymmetric types of resonators: cylinder, cone and cylinder
      cone under the same operation conditions. Pressure ratios in the prime mover were
      observed, 1.15 for cylinder-cone, 1.092 for cylinder and 1.097 for cone. The
      acoustic fields along the looped tube and different types of resonators were
      calculated, which agreed well with the measured results.

PMID- 16987535
TI  - Evolutionary game dynamics in finite populations with strong selection and weak
      mutation.
AB  - We study stochastic game dynamics in finite populations. To this end we extend
      the classical Moran process to incorporate frequency-dependent selection and
      mutation. For 2 x 2 games, we give a complete analysis of the long-run behavior
      when mutation rates are small. For 3 x 3 coordination games, we provide a simple
      rule to determine which strategy will be selected in large populations. The
      expected motion in our model resembles the standard replicator dynamics when the
      population is large, but is qualitatively different when the population is small.
      Our analysis shows that even in large finite populations the behavior of a
      replicator-like system can be different from that of the standard replicator
      dynamics. As an application, we consider selective language dynamics. We
      determine which language will be spoken in finite large populations. The results
      have an intuitive interpretation but would not be expected from an analysis of
      the replicator dynamics.

PMID- 16987538
TI  - Energy flow measurements in acoustic waves in a duct.
AB  - Where, how much and how efficiently the energy conversion takes place in a
      regenerator of a thermoacoustic engine are expressed using the axial distribution
      of acoustic work flow and heat flow. As a first step in determining the energy
      flows inside the regenerator, measuring methods of the work flow are briefly
      described and the experimental results in an acoustic resonator are shown.
      Applicability of these methods to the regenerator is discussed.

PMID- 16987537
TI  - Vibration analysis and sound field characteristics of a tubular ultrasonic
      radiator.
AB  - A sort of tubular ultrasonic radiator used in ultrasonic liquid processing is
      studied. The frequency equation of the tubular radiator is derived, and its
      radiated sound field in cylindrical reactor is calculated using finite element
      method and recorded by means of aluminum foil erosion. The results indicate that
      sound field of tubular ultrasonic radiator in cylindrical reactor appears
      standing waves along both its radial direction and axial direction, and
      amplitudes of standing waves decrease gradually along its radial direction, and
      the numbers of standing waves along its axial direction are equal to the axial
      wave numbers of tubular radiator. The experimental results are in good agreement
      with calculated results.

PMID- 16987539
TI  - Localizing the reovirus packaging signals using an engineered m1 and s2 ssRNA.
AB  - Using in vitro engineered and transcribed reovirus m1 and s2 ssRNAs, we
      demonstrate that the nucleotides used to identify these ssRNAs are localized to
      the 5' and not the 3' termini. To demonstrate this, we used our previously
      reported S2-CAT reovirus and we report the creation of an engineered M1-CAT
      reovirus. The M1 gene of this virus retains 124 nucleotides from the wild type M1
      gene preceding the CAT gene and 172 nucleotides from the wild type gene following
      the CAT gene. The engineered M1-CAT ssRNA is 1048 nucleotides in length, much
      shorter than the wild type M1 at 2304 nucleotides. We have used a set of chimeric
      s2.m1 ssRNAs to localize the packaging signals within these RNAs. By packaging
      signals we mean that the presence of these signals in engineered ssRNAs results
      in these ssRNAs being replicated to dsRNA and packaged into progeny virus. An
      engineered ssRNA with a 5' sequence identical with the wild type s2 ssRNA,
      supported by a 3' sequence from either the m1 or s2 ssRNA, is incorporated into a
      virus as an S2 dsRNA. Likewise, an ssRNA with an m1 5' end is incorporated as an
      M1 dsRNA.

PMID- 16987540
TI  - Modeling-based characterization of the elicitor function of amino acid 461 of
      Cucumber mosaic virus 1a protein in the hypersensitive response.
AB  - The Ns strain of Cucumber mosaic virus (CMV) induces hypersensitive response (HR)
      on Nicotiana tabacum cv. Xanthi-nc and on Nicotiana glutinosa. The genetic
      determinant of the HR induction was localized earlier to amino acid 461 of the 1a
      protein. The 3D structure of the 1a protein is still unknown and building a
      homology model is impossible. Nevertheless, on the basis of secondary structure
      predictions we have created partial protein models for the region surrounding
      residue 461 which can account structurally for the effect of aa 461 on elicitor
      function. Seven different amino acid mutations were designed and introduced to
      the position 461 of the 1a protein in RNA 1. Three of the mutations (proline,
      glutamic acid, asparagine) inhibited virus replication. Two of the mutants caused
      systemic symptom development (lysine and arginine). Two mutants (alanine and
      serine) resulted in localization of the virus, but strong necrosis similar to the
      original Ns-CMV strain was not observed. Inoculation of purified Ns-CMV virions
      at extremely high concentration provoked systemic symptoms.

PMID- 16987541
TI  - Hydrolysis and acidification of waste activated sludge at different pHs.
AB  - The effect of pH from 4.0 to 11.0 on the hydrolysis and acidification of waste
      activated sludge (WAS) was investigated. Experimental results showed that at room
      temperature the sludge hydrolysis was in the following order:
      alkaline>acidic>(neutral and blank test), and between pH 6.0 and 11.0 the sludge
      hydrolysis increased with pH. The three main components, soluble protein,
      carbohydrate and volatile fatty acids (VFAs) in the hydrolytic product were
      analyzed. It was observed that both the soluble protein and carbohydrate
      increased with pH in the pH range 7.0-11.0, but also increased to a smaller
      extent with pH from 7.0 to 4.0. The VFAs concentration was also affected by pH.
      Under alkaline conditions, the VFAs production was significantly higher than
      under other conditions. The concentration of VFAs on the 8th day of fermentation
      at pH 4.0, 7.0 and 10.0 was, respectively, 354.49, 842.00 and 2708.02 mg/L, while
      VFAs in the blank test was only 633.59 mg/L. The VFAs consisted of acetic,
      propionic, iso-butyric, n-butyric, iso-valeric and n-valeric acids, but acetic,
      propionic and iso-valeric were the three main products. Also, the release of
      soluble phosphorus and ammonia and the production of methane was studied during
      WAS fermentation at different pHs.

PMID- 16987542
TI  - Adsorption studies of recalcitrant compounds of molasses spentwash on activated
      carbons.
AB  - Due to high levels of residual chemical oxygen demand (COD) in the effluent of
      molasses spentwash (MSW) after anaerobic treatment, acceptable COD levels for
      discharge cannot be achieved without some form of post-treatment. In this study,
      the particulate composition of molasses spentwash after anaerobic digestion
      (MSWD), is characterised as to its particle size distribution, using micro- and
      ultrafiltration and three activated carbons are characterised as to their ability
      to reduce significantly the COD of MSWD effluent. The activated carbons tested as
      adsorbent, were characterised by XPS spectroscopy, elemental analysis, surface
      area, pore size distribution, and acid-base titration using the Boehm's method.
      Adsorption of phenol, used here as a reference compound, and of some organic
      compounds contained in MSWD (gallic acid, tannic acid, and melanoidin,
      respectively), was studied. It was clearly demonstrated that an activated carbon
      with a significant distribution of both micropores and mesopores and a
      significant amount of macropores that are assumed to act as conduits providing
      access to micro- and mesopores, have a good adsorption efficiency for compounds
      such as tannic acid and melanoidins. It is a good adsorbent for melanoidin and
      coloured compounds of MSWD, which represents a large source of the aqueous
      pollution in sugar cane industries.

PMID- 16987543
TI  - Concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated
      dibenzofurans, and non-ortho and mono-ortho polychlorinated biphenyls in blood of
      Yusho patients.
AB  - We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs), non-ortho polychlorinated biphenyls (non
      ortho PCBs) and mono-ortho polychlorinated biphenyls (mono-ortho PCBs) in blood
      collected from 279 Yusho patients living in Japan, 92 Yusho-suspected persons
      living in Japan and 127 normal controls living in Fukuoka Prefecture, and
      compared among the groups in terms the concentrations of these compounds. The
      total toxic equivalents (TEQ) concentrations of PCDDs, PCDFs, non-ortho PCBs, and
      mono-ortho PCBs in the bloods of Yusho patients and Yusho-suspected persons were
      161.4 and 51.2 pg TEQ/g lipid, respectively and were about 3.5 and 1.1 times
      higher than those of normal controls, respectively. Although the TEQ
      concentrations of PCDDs, non-ortho PCBs, and mono-ortho PCBs among Yusho
      patients, Yusho-suspected persons and normal controls were nearly the same, the
      PCDFs levels of Yusho patients were significantly higher than those of Yusho
      suspected persons and about 10.3 times higher than those of normal controls. In
      Yusho patients, PCDFs contributed about 65% to the total TEQ concentration. Among
      the PCDFs congeners for Yusho patients, the concentration of 2,3,4,7,8
      pentachlorodibenzofuran (PeCDF) was about 11.3 times higher than that of normal
      controls. These findings indicated that Yusho patients even now, more than 34
      years after the outbreak of Yusho, have much higher blood levels of 2,3,4,7,8
      PeCDF in general than do unaffected persons.

PMID- 16987544
TI  - Long-term survival of 106 stage III ovarian cancer patients with minimal residual
      disease after second-look laparotomy and consolidation radiotherapy.
AB  - OBJECTIVE: Attempts to increase survival in stage III ovarian cancer patients
      with minimal residual disease at second-look laparotomy have included
      consolidation radiotherapy. We present long-term survival of 106 consecutive
      patients treated between 1983 and 1993 in 4 French institutions for stage III
      ovarian adenocarcinoma with first-look debulking, cisplatin-based chemotherapy,
      second-look surgery with a residual disease <1 cm and consolidation radiotherapy.
      METHODS: Median age was 52 years. Residual disease after first look surgery was
      <1 cm for 40.5% of patients. Median number of chemotherapy cycles was 6 (range 4
      12). Residual disease <1 cm at second-look laparotomy was observed in 79% of the
      patients, with 33% of patients in complete histologic remission. Residual disease
      <1 cm was obtained in all patients after tumor excision during second-look
      surgery. Radiation was performed using a linear accelerator with a whole abdomen
      dose of 22.5 Gy, an additional 22 Gy pelvic boost for 71 patients, and an
      additional 12 Gy lombo-aortic boost for 33 patients. RESULTS: Median follow-up
      was 14 years. Radiation was stopped for acute toxicity in 11 patients. Long-term
      toxicities included radiation enteritis in 21 patients with 9 patients requiring
      surgery for bowel obstruction. Four deaths were related to enteritis
      complications. Overall survival at 5 and 10 years was respectively 53% and 36%.
      CONCLUSION: This sequential treatment with final consolidation abdominopelvic
      radiotherapy is an effective treatment for a selected group of stage III ovarian
      cancer patients with a high intestinal toxicity incidence.

PMID- 16987545
TI  - A study of the lasting effects of cocaine pre-exposure on anxiety-like behaviors
      under baseline conditions and in response to central injections of corticotropin
      releasing factor.
AB  - Anxiety-like behaviors emerge with repeated exposure to and short-term withdrawal
      from cocaine. The stress-related neuropeptide, corticotropin-releasing factor
      (CRF), has been implicated in the anxiogenic effects of cocaine withdrawal, as
      well as in some of the long-lasting effects of cocaine. One objective of the
      present experiments was to determine whether repeated exposures to cocaine, under
      conditions that induce anxiety in the initial withdrawal period, would induce
      longer-lasting anxiogenic responses. A second objective was to determine whether
      any such effects would be potentiated by CRF. In Experiment 1, animals were
      injected once daily for 7 days with cocaine (30 mg/kg, i.p.) or saline in the
      home cages and, after a 10-day drug-free period, were given an i.c.v. injection
      of CRF (0.5 or 5.0 micro g) or vehicle, followed by a 5-min test for anxiety in
      the elevated plus maze or light-dark transition apparatus. In Experiment 2,
      animals were given the cocaine or saline injections in a distinct environment. At
      test, they were placed in the distinct environment after the CRF (0.5 micro g) or
      vehicle injection and were subsequently tested for anxiety. Cocaine produced
      enhanced levels of anxiety when pre-exposures were given in a distinct
      environment, but not when they were given in the home cage. In neither case did
      cocaine differentially alter anxiety-like responses to CRF. The results suggest
      that a "reminder" of the drug experience, such as re-exposure to cocaine-paired
      contextual cues, may be necessary to induce elevated levels of anxiety after the
      initial withdrawal period. In addition, although the results do not rule out a
      role for endogenous CRF in lasting cocaine-induced anxiogenic responses, they
      suggest that an increased sensitivity of CRF receptors to the peptide is not
      responsible for the effect.

PMID- 16987546
TI  - Beneficial effects of galantamine on performance in the object recognition task
      in Swiss mice: deficits induced by scopolamine and by prolonging the retention
      interval.
AB  - Episodic memory has been found to be impaired in several neuropsychiatric
      disorders. The object recognition task (ORT), introduced by Ennaceur and Delacour
      [Ennaceur A., Delacour J. A new one-trial test for neurobiological studies of
      memory in rats: 1. Behavioral data. Behav Brain Res 1988; 31: 47-59.], is a
      method to measure a specific form of episodic memory in rats and mice. It is
      based on the spontaneous behavior of rodents and can be considered as a retention
      test completely free of reference memory components. Therefore, the ORT has been
      increasingly used as an experimental tool in assessing drug effects on memory and
      investigating the neural mechanisms underlying learning and memory. In the
      present study, the main goal was to evaluate the effects of galantamine in Swiss
      mice in the ORT on scopolamine-induced deficits and with different retention
      intervals. Mice had a good object recognition memory at the 15 min retention
      intertrial interval (ITI). Object discrimination was absent at the longer
      intervals (1 h, 4 h and 24 h). Galantamine (10 mg/kg, administered s.c., 30 min
      prior to acquisition) partially reversed effects of scopolamine (0.63 mg/kg,
      administered s.c., 30 min prior to acquisition) and normalized performance to
      control levels. A lower dose of galantamine (0.63 mg/kg) was also investigated
      when two different retention intervals (15 min and 1 h) were used. Galantamine
      (0.63 mg/kg) had no adverse effects. Solvent-treated mice in the 1 h ITI
      condition did not discriminate between the novel and the familiar object
      (discrimination index was equal to zero), while galantamine (0.63 mg/kg)-treated
      mice attained a good object recognition memory performance. In conclusion,
      galantamine was shown to possess memory-enhancing effects in two conditions that
      reduced object discrimination: scopolamine-induced deficits and when a longer
      retention interval was used.

PMID- 16987547
TI  - Batchwise assessment of porcine embryos for cryotolerance.
AB  - The viability or developmental ability of porcine embryos after slow-freezing and
      thawing differs depending on the embryonic stage or the batch, which is defined
      as a group of embryos obtained from one donor at one time. We froze porcine
      blastocysts in batches and assessed their cryotolerance by using two expanded
      blastocysts (EBs) as samples to predict the developmental potential of other
      blastocysts from the same batch at different stages. Two EBs from the same batch
      that had been separately frozen were thawed and cultured in vitro for 48 h to
      examine their in vitro ability to develop to the hatched blastocyst stage.
      Thereafter, each batch was assigned to Grade A, B, or C according to the
      viability of the two EBs, i.e., 100% viability (2/2: number of hatched
      blastocysts/number of cultured EBs) was Grade A; 50% (1/2) was Grade B; and 0%
      (0/2) was Grade C. The viability of EBs after freeze-thawing and in vitro culture
      varied depending on the batch and was lower (31.0+/-10.2%, mean+/-S.E.M.; P<0.01)
      than that of unfrozen controls (96.8+/-2.3%). The viability of frozen-thawed
      hatched blastocysts (HBs) did not differ among the graded batches, but the
      blastocyst diameter decreased (from 409 to 326 microm) as the batch grade
      decreased (from A to C). When both EBs and HBs from batches of the same grade
      were transferred to recipients (average 11.7 EBs and 16.0 HBs per recipient), the
      rate of pregnancy and farrowing in recipients decreased (from 77.8% to 0%) and
      the number of piglets obtained decreased (from 15.3 to 0) as the batch grade
      decreased. However, when not only frozen-thawed EBs from Grade B or C batches,
      but also four helper embryos at the morula to early blastocyst stage (which were
      expected to support the pregnancy) were transferred, the number of piglets
      generated was higher from EBs from Grade B batches (16.0) than from EBs from
      Grade C batches (0.0). When frozen-thawed HBs and helper embryos were
      transferred, the number of piglets generated was higher from HBs from Grade B
      batches (12.7) than that from HBs from Grade C batches (1.9). After slow-freezing
      of porcine blastocysts, their rate of survival to the piglet stage differs
      batchwise, and in vitro viability assessment of sample EBs after freezing and
      thawing may help in assessing the post-freezing and post-thawing developmental
      potential of other blastocysts at different stages from the same batch.

PMID- 16987548
TI  - Semen production in two rabbit lines divergently selected for 63-d body weight.
AB  - Thirty-one bucks from two lines divergently selected for 63-d body weight (low, L
      and high, H) were solicited every week (twice at a 15min interval) during 18
      weeks resulting in 482 ejaculates. While differing markedly on adult body weight
      (L: 4650g versus H: 5925g), both lines had the same testis weight. Libido did not
      differ between the lines. The proportion of ejaculates suitable for insemination
      was markedly higher in the L line (66.5% versus 44.2%). Mass motility and the
      volume of the ejaculates were higher in the L line while the sperm concentration
      was higher in the H line. Overall, the total number of spermatozoa per ejaculate
      was similar in both lines but the efficient number of spermatozoa per ejaculate,
      a synthetic criterion taking into account the ability of the ejaculate for
      insemination was higher in the L line (229 versus 170x10(6)). The L line had
      higher values of average path velocity, linearity and curvilinear velocity but a
      lower value of beat cross frequency. In the L line, both ejaculates had the same
      concentration, while in the H line, the first ejaculate was more concentrated
      than the second one. Some male reproductive traits are therefore genetically
      related to body weight.

PMID- 16987549
TI  - An alternative simple method for mass production of chimeric embryos by
      coculturing denuded embryos and embryonic stem cells in Eppendorf vials.
AB  - The generation of germline competent chimeric mice via embryonic stem (ES) cells
      is a crucial step in developing gene-manipulated mouse models. To date,
      techniques for generating chimeric mice include direct microinjection of ES cells
      into the cavity of 3.5-d post-coitum (dpc) blastocysts and aggregating or
      coculturing 2.5 dpc zona pellucida-free (denuded) embryos with ES cells. We
      present here a procedure that is simple and reproducible for mass producing (10
      150 embryos/vial/time) chimeric embryos by coculturing denuded 8-cell embryos and
      morula in 0.8 mL KSOM-AA medium containing 5 x 10(5)mL-1 purified green
      fluorescence protein-expressing ES cells (either fresh or thawed) in an 1.7 mL
      Eppendorf vial for 3h. The resulting chimeras had substantial levels of chimerism
      and high germline transmission rates. Therefore, the method developed in this
      study can provide a simple and mass reproducible alternative method (to germline
      transmitter chimeric mice), without technological and instrumental difficulties,
      for generating chimeric embryos.

PMID- 16987550
TI  - Physicochemically modified silicon as a substrate for protein microarrays.
AB  - Reverse phase protein microarrays (RPMA) enable high throughput screening of
      posttranslational modifications of important signaling proteins within diseased
      cells. One limitation of protein-based molecular profiling is the lack of a PCR
      like intrinsic amplification system for proteins. Enhancement of protein
      microarray sensitivities is an important goal, especially because many molecular
      targets within patient tissues are of low abundance. The ideal array substrate
      will have a high protein-binding affinity and low intrinsic signal. To date,
      nitrocellulose-coated glass has provided an effective substrate for protein
      binding in the microarray format when using chromogenic detection systems. As
      fluorescent systems, such as quantum dots, are explored as potential reporter
      agents, the intrinsic fluorescent properties of nitrocellulose-coated glass
      slides limit the ability to image microarrays for extended periods of time where
      increases in net sensitivity can be attained. Silicon, with low intrinsic
      autofluorescence, is being explored as a potential microarray surface. Native
      silicon has low binding potential. Through titrated reactive ion etching (RIE),
      varying surface areas have been created on silicon in order to enhance protein
      binding. Further, via chemical modification, reactive groups have been added to
      the surfaces for comparison of relative protein binding. Using this combinatorial
      method of surface roughening and surface coating, 3-aminopropyltriethoxysilane
      (APTES) and mercaptopropyltrimethoxysilane (MPTMS) treatments were shown to
      transform native silicon into a protein-binding substrate comparable to
      nitrocellulose.

PMID- 16987551
TI  - A novel tracing algorithm for high throughput imaging Screening of neuron-based
      assays.
AB  - High throughput neuron image processing is an important method for drug screening
      and quantitative neurobiological studies. The method usually includes detection
      of neurite structures, feature extraction, quantification, and statistical
      analysis. In this paper, we present a new algorithm for fast and automatic
      extraction of neurite structures in microscopy neuron images. The algorithm is
      based on novel methods for soma segmentation, seed point detection, recursive
      center-line detection, and 2D curve smoothing. The algorithm is fully automatic
      without any human interaction, and robust enough for usage on images with poor
      quality, such as those with low contrast or low signal-to-noise ratio. It is able
      to completely and accurately extract neurite segments in neuron images with
      highly complicated neurite structures. Robustness comes from the use of 2D
      smoothening techniques and the idea of center-line extraction by estimating the
      surrounding edges. Efficiency is achieved by processing only pixels that are
      close enough to the line structures, and by carefully chosen stopping conditions.
      These make the proposed approach suitable for demanding image processing tasks in
      high throughput screening of neuron-based assays. Detailed results on
      experimental validation of the proposed method and on its comparative performance
      with other proposed schemes are included.

PMID- 16987552
TI  - Introducing an alternative biophysical method to analyze direct G protein
      regulation of voltage-dependent calcium channels.
AB  - Direct G protein inhibition of voltage-dependent calcium channels is currently
      indirectly assessed by the gain of current produced by depolarizing prepulse
      potentials (PP). Indeed, PPs produce a channel opening- and time-dependent
      dissociation of G proteins from the channel that is responsible for the increase
      in Ca(2+) permeation. Parameters of G protein dissociation are essential to
      describe the characteristic landmark modifications in channel activities that
      underlie G protein regulation. From the kinetics and opening-dependence of this
      dissociation, crucial biophysical parameters are extracted such as the extent and
      the rate of G protein unbinding from the channel. Unfortunately, the method used
      so far assumes that G protein regulated channels undergo the same inactivation
      kinetics than control channels. Herein, we demonstrate for the first time that G
      protein-bound channels undergo a much slower inactivation than control channels.
      We thus introduce a novel simple-to-use method that avoids the use of PPs and
      that is not affected by potential changes in channel inactivation kinetics
      conferred by G protein binding. This method extracts G protein unbinding
      parameters from ionic currents induced by regular depolarizing pulses by
      separating the ionic currents due to non-regulated channels from the ionic
      currents that result from a progressive departure of G proteins from regulated
      channels.

PMID- 16987553
TI  - Analysis of the interaction between IFN-gamma and IFN-gammaR in the effector
      phase of experimental murine allergic conjunctivitis.
AB  - IFN-gamma acts to promote the severity of experimental allergic conjunctivitis
      (EC) during the effector phase. To identify the cell source and cell target of
      this cytokine in the effector phase of EC, we established mice lacking both IFN
      gamma and the IFN-gamma receptor (Dbl-KO). Reciprocal adoptive transfer
      experiments involving wild-type, Dbl-KO, IFN-gamma-lacking and IFN-gammaR-lacking
      mice were performed. EC was then induced by RW challenge in eye drops. Analysis
      of the resulting eosinophil infiltration in the six donor/recipient combinations
      revealed that IFN-gamma produced by both donor and recipient cells plays an
      important role in the EC effector phase, and that the targets for this cytokine
      are also both donor and recipient cells. That EC was attenuated when any of the
      IFN-gamma-IFN-gammaR interactions were disturbed confirms that IFN-gamma promotes
      the severity of EC during the effector phase. These observations indicate that
      Dbl-KO mice will be useful for investigating the role(s) IFN-gamma play in
      inflammatory diseases.

PMID- 16987554
TI  - Vascular endothelial growth factor and children featuring nasal polyps.
AB  - BACKGROUND: The aim of this study is to explore the expression of vascular
      endothelial growth factor within nasal polyps, and the implication of such
      expression as regards the development of nasal polyps amongst children. MATERIAL
      AND METHODS: Sixty children suffering from chronic rhinosinusitis were enrolled
      in this study. Amongst them, 30 patients featured rhinosinusitis with associated
      nasal polyps. A biopsy specimen was taken from the stalk or the base of the nasal
      polyp for nasal-polyp sufferers, and the ethmoid sinus for study participants who
      featured no nasal polyps. The primary lesions biopsied were immunohistochemically
      stained with a specific endothelial-cell marker and also stained for the presence
      of vascular endothelial growth factor. The specific level of vascular endothelial
      growth factor and the mean number of blood vessels present in a visual
      microscopic (biopsied-specimen) field were calculated under light microscopy
      (x400). RESULTS: The number of vascular endothelial growth factor-expressing
      cells for the nasal-polyp group and for the sinusitis group was, respectively,
      20.8+/-4.0 and 11.5+/-3.4 per visual field. Correspondingly, the mean intra-polyp
      blood-vessel density for the nasal-polyp group and that for the control group
      was, respectively, 10.5+/-2.6 and 5.0+/-1.9 per visual field. The mean intra
      polyp blood-vessel density and the number of vascular endothelial growth factor
      expressing cells proved to be significantly greater amongst individuals from the
      nasal-polyp group than was the case for their analogs from the sinusitis group
      (P<0.01, for both). The presence of vascular endothelial growth factor was found
      to be distributed predominantly within the vascular endothelium and the mast
      cells of polyp tissue. In addition, the level of vascular endothelial growth
      factor expression and the mean blood-vessel count per field correlated
      significantly for nasal-polyp tissue (P<0.001). Furthermore, the relative size of
      nasal polyps correlated significantly with the number of (intra-polyp) vascular
      endothelial-cell growth factor-expressing cells and the mean blood-vessel density
      (P<0.05, for both). CONCLUSION: The level of expression of vascular endothelial
      cell growth factor (VEGF) and the mean blood-vessel density were shown to be
      significantly greater within nasal polyps than within corresponding sinusitis
      mucosa. Clinically, the expression of both of these parameters correlated well
      with the relative size of nasal polyps. Vascular endothelial growth factor
      participates in the formation of nasal polyps amongst children suffering from
      chronic rhinosinusitis (CRS).

PMID- 16987555
TI  - Antiviral activity of CHO-SS cell-derived human omega interferon and other human
      interferons against HCV RNA replicons and related viruses.
AB  - The fully glycosylated human omega interferon produced from CHO-SS cells
      (glycosylated IFN-omega) has been shown to be well-tolerated in man and to induce
      a sustained virologic response in patients infected with hepatitis C virus (HCV).
      We examined the antiviral activity of glycosylated IFN-omega and various human
      IFNs (IFN-alpha, -beta, -gamma and non-glycosylated bacterial (Escherichia coli)
      recombinant IFN-omega (non-glycosylated IFN-omega)) against HCV RNA replicons and
      several viruses related to HCV. Since none of the IFNs displayed cytotoxicity we
      compared their activities based on the effective concentration of the IFN that
      inhibited virus growth by 50% (EC50). Glycosylated IFN-omega was found to be the
      most potent antiviral agent of all the IFNs tested against bovine viral diarrhea
      virus (BVDV), yellow fever virus and West Nile virus. With HCV RNA replicons, non
      glycosylated IFN-omega was comparable in activity to IFN-alpha while glycosylated
      IFN-omega was markedly more potent, indicating that glycosylation has an
      important effect on its activity. Drug combination analysis of glycosylated IFN
      omega+ribavirin (RBV) in BVDV showed a synergy of antiviral effects similar to
      IFN-alpha+RBV, as well as a unique antagonism of RBV cytotoxic effects by
      glycosylated IFN-omega. Transcription factor (TF) profiling indicated that IFN
      alpha or glycosylated IFN-omega treatment upregulated the same 17 TFs. IFN-alpha
      and glycosylated IFN-omega also upregulated 9 and 40 additional unique TFs,
      respectively. The differences in the expression of these TFs were modest, but
      statistically significantly different for eight of the TFs that were upregulated
      exclusively by glycosylated IFN-omega. The activation of these additional TFs by
      glycosylated IFN-omega might contribute to its high potency.

PMID- 16987556
TI  - Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in developing red
      seabream (Pagrus major) embryo: an association of morphological deformities with
      AHR1, AHR2 and CYP1A expressions.
AB  - The toxicity of dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is
      mainly mediated by the aryl hydrocarbon receptor (AHR), which regulates the
      multiple target genes including cytochrome P4501A (CYP1A). In general, bony
      fishes, which possess at least two distinct AHRs are one of the most sensitive
      vertebrates to TCDD in early life stage. However, the physiological and
      toxicological roles of piscine multiple AHRs are not fully understood, especially
      in marine fish. To understand which AHR is responsible for TCDD toxicity in a
      marine fish species, we characterized the early life stage toxicity related to
      the expression of AHRs and CYP1A in red seabream (Pagrus major). The embryos at
      10h post-fertilization (hpf) were treated with 0-100 microg/L TCDD for 80 min
      waterborne exposure. TCDD dose-dependently elicited developmental toxicities
      including mortality, yolk sac edema, retarded body growth, spinal deformity,
      reduced heart rate, shortened snout, underdeveloped fin, heart, and lower jaw.
      Intriguingly, hemorrhage and pericardium edema, typical TCDD developmental
      defects noticed in other fish species, were not found in red seabream until test
      termination. The EC(egg)50s for yolk sac edema, underdeveloped fin, and spinal
      deformity were 170, 240, and 340 pg/g, respectively. The LC(egg)50 was 360 pg/g
      embryo, indicating that this species is one of the most sensitive fishes to TCDD
      toxicity. The expression levels of rsAHR1, rsAHR2 and CYP1A mRNAs were also
      determined in different developmental stages. The rsAHR2 mRNA expression dose
      dependently increased following TCDD exposure, while rsAHR1 mRNA level was not
      altered. Level of rsAHR2 mRNA measured by two-step real-time PCR was 30 times
      higher than rsAHR1 in embryos treated with the highest dose. Temporal patterns of
      rsAHR2 and CYP1A mRNAs were similar in TCDD-treated embryos, representing a
      significant positive correlation between rsAHR2 and CYP1A mRNA levels, but not
      between rsAHR1 and CYP1A. In comparison of temporal trends of TCDD-induced AHRs
      and CYP1A expression, and developmental toxicities, the highest expression of
      rsAHR2 and CYP1A mRNA were detected prior to the appearance of maximal incidence
      of TCDD toxic manifestations. These results suggest that rsAHR2 may be dominantly
      involved in the transcriptional regulation of CYP1A, and several TCDD defects are
      dependent on the alteration of rsAHR2 and/or rsAHR2-CYP1A signaling pathway that
      is controlled through their expression levels.

PMID- 16987557
TI  - Expression and function of pvcrt-o, a Plasmodium vivax ortholog of pfcrt, in
      Plasmodium falciparum and Dictyostelium discoideum.
AB  - Chloroquine resistance in Plasmodium vivax threatens the use of this drug as
      first-line treatment for millions of people infected each year worldwide. Unlike
      Plasmodium falciparum, in which chloroquine resistance is associated with
      mutations in the pfcrt gene encoding a digestive vacuole transmembrane protein,
      no point mutations have been associated with chloroquine resistance in the P.
      vivax ortholog gene, pvcrt-o (also called pvcg10). However, the question remains
      whether pvcrt-o can affect chloroquine response independent of mutations. Since
      P. vivax cannot be cultured in vitro, we used two heterologous expression systems
      to address this question. Results from the first system, in which chloroquine
      sensitive P. falciparum parasites were transformed with pvcrt-o, showed a 2.2
      fold increase in chloroquine tolerance with pvcrt-o expression under a strong
      promoter; this effect was reversed by verapamil. In the second system, wild type
      pvcrt-o or a mutated form of the gene was expressed in Dictyostelium discoideum.
      Forms of PvCRT-o engineered to express either lysine or threonine at position 76
      produced a verapamil-reversible reduction of chloroquine accumulation in this
      system to approximately 60% of that in control cells. Our data support an effect
      of PvCRT-o on chloroquine transport and/or accumulation by P. vivax, independent
      of the K76T amino acid substitution.

PMID- 16987558
TI  - Hyper-activated IRF-1 and STAT1 contribute to enhanced interferon stimulated gene
      (ISG) expression by interferon alpha and gamma co-treatment in human hepatoma
      cells.
AB  - Previous reports suggest that type I and type II Interferon can co-operatively
      inhibit some virus replication, e.g. HCV, SARS-CoV, HSV-1. To find out the
      molecular mechanism underlying this phenomenon, we analyzed the transcription
      profile stimulated by IFN-alpha and IFN-gamma in Huh-7 cells and found that the
      transcription of a subset of IFN stimulated genes (ISGs) including BclG, XAF1,
      TRAIL and TAP1 was enhanced when IFN-alpha and gamma were both present. Promoter
      analysis of BclG revealed that IRF-1 and STAT1 were both required in this
      process. Enhanced IRF-1/DNA complex formation was observed in interferon co
      treatment group by gel shift analysis. Furthermore, IRF-1 activation was found to
      be generally required in this cluster of ISGs. STAT1 tyrosine phosphorylation was
      elevated by IFN combination treatment, however, only the hyper-transactivation of
      GAS but not ISRE was observed. In conclusion, hyper-activation of IRF-1 and
      elevated STAT1 dimer formation may be two general switches which contribute to a
      much more robust antiviral symphony against virus replication when type I and
      type II IFNs are co-administered.

PMID- 16987559
TI  - Calcium transients and calcium signalling during early neurogenesis in the
      amphibian embryo Xenopus laevis.
AB  - Development of the vertebrate embryonic nervous system is characterized by a
      cascade of signalling events. In Xenopus, the initial step in this cascade
      results from signals emanating from the dorsal mesoderm that divert the fate of
      the ectoderm from an epidermal to a neural lineage. These signals include
      extracellular antagonists of the bone morphogenetic protein (BMP). Experiments
      performed with isolated ectoderm suggest that epidermis is induced by BMP,
      whereas neural fates arise by default following BMP inhibition; however, we show
      that this mechanism is not sufficient for neural determination. Ca2+ imaging of
      intact Xenopus embryos reveals patterns of Ca2+ transients in the dorsal ectoderm
      but not in the ventral ectoderm. These increases in intracellular calcium
      concentration ([Ca2+](i)), which occur via the activation of dihydropyridine
      (DHP)-sensitive Ca2+ channels, are necessary and sufficient to orientate the
      ectodermal cells toward a neural fate. On the one hand, the treatments that
      antagonize the increase in [Ca2+](i), inhibit neuralization, while on the other
      hand, an artificial increase in [Ca2+](i), whatever its origin, neuralizes the
      ectoderm. Using these properties, we have constructed a subtractive cDNA library
      between untreated ectoderm and caffeine-treated ectoderm. The caffeine stimulates
      an increase in [Ca2+](i) and thus orientates the cells towards the neural
      pathway. We have identified early Ca2+ target genes expressed in neural
      territories. One of these genes, an arginine methyl transferase, controls the
      expression of the early proneural gene, Zic3. Here, we discuss an alternative
      model where Ca2+ plays a central regulatory role in early neurogenesis. This
      model integrates the activation of a Ca2+ -dependent signalling pathway due to an
      influx of Ca2+ through DHP-Ca2+ channels. While Ca2+ is required for neural
      determination, epidermal determination occurs when Ca2+ -dependent signalling
      pathways are inactive.

PMID- 16987560
TI  - Site specific differential activation of ras/raf/ERK signaling in rabbit
      isoproterenol-induced left ventricular hypertrophy.
AB  - To understand better the mediating role of ras/raf/ERK signaling pathway in
      development of cardiac hypertrophy and cerebrovascular events in vivo, the
      molecular mechanism of the pathway in heart and cerebral arteries after
      isoproterenol (ISO) induced beta-adrenergic receptor (betaAR) stimulation was
      examined in rabbit as animal model. Compared with the heart, our findings
      indicate that ISO-stimulation results in increase in mRNA levels of ras, raf, and
      immediate-early genes in the cerebral arteries. Conversely, the ras and raf
      protein expression levels (determined by Western blot) and the ras-GTP level
      (determined by pull-down assay) in the heart, but not the cerebral arteries, are
      markedly elevated after treatment. In addition, despite constant ERK1/2
      abundance, phosphorylated ERK (pERK) activity was elevated at both sites with
      prominent effect on heart following stimulation. Opposing to the PKA and PKC, as
      upstream contributors in the pathway, which seem to be similarly affected at both
      sites following ISO-stimulation, the results imply that the downstream candidates
      ras and raf, as well as immediate-early genes, have different responses at both
      sites post-stimulation. The results provide an evidence of site-dependent
      differential response of ras/raf/ERK pathway after cardiac hypertrophy-induced by
      ISO-stimulation. This varied response may account for underlying mechanisms of
      development of cardiac hypertrophy and cerebrovascular events in heart and
      cerebral arteries, respectively.

PMID- 16987561
TI  - Pulsed electric fields cause bacterial envelopes permeabilization depending on
      the treatment intensity, the treatment medium pH and the microorganism
      investigated.
AB  - The relationship between membrane permeabilization and loss of viability by
      pulsed electric fields (PEF) depending on the treatment intensity and the
      treatment media pH in two gram-positive (Lactobacillus plantarum, Listeria
      monocytogenes) and two gram-negative (Escherichia coli, Salmonella senftenberg
      775W) bacterial species has been investigated. Loss of membrane integrity was
      measured as increased uptake of the fluorescent dye propidium iodide (PI). Non
      permanent/reversible permeabilization was detected when cells stained with PI
      during PEF resulted in higher fluorescence than that measured in cells stained
      after PEF. Whereas loss of viability of the two gram-negative bacteria was
      correlated with the sum of non-permanent and permanent membrane permeabilization
      when treated at pH 7.0, in the case of the two gram-positives, loss of viability
      was correlated with a permanent loss of membrane integrity. At pH 7.0, the four
      bacteria exhibited reversible permeabilization. However, whereas the gram
      positives capable of reversing permeabilization survived, the gram-negative cells
      died, despite their capacity to reverse permeabilization immediately after PEF.
      Thus, resealing is not necessarily related to the survival of PEF-treated cells.
      In contrast, when cells were PEF-treated at pH 4.0 a more complicated picture
      emerged. Whereas loss of viability was correlated with a permanent loss of
      membrane integrity in L. monocytogenes cells, in L. plantarum the degree of
      permeabilization was higher, and in the gram-negative strains, much lower than
      the percentage of inactivated cells. These results support the view that membrane
      permeabilization is involved in the mechanism of bacterial inactivation by PEF,
      but the nature of membrane damage and its relationship with cell death depends on
      the bacterial species and the treatment medium pH.

PMID- 16987562
TI  - Cloning and recombinant expression of a crustin-like gene from Chinese shrimp,
      Fenneropenaeus chinensis.
AB  - Antimicrobial peptides or proteins (AMPs) are proved to be one of the most
      important humoral factors to resist pathogen infection. As an antimicrobial
      protein, crustin had been described in invertebrates as a component of the innate
      immune system. A crustin-like gene (CruFc) was cloned from haemocytes of Chinese
      shrimp Fenneropenaeus chinensis by 3' and 5'-RACE PCR. The full-length cDNA
      consists of 523 with 405 bp open reading frame encoding 134 amino acids and the
      deduced peptide contains a putative signal peptide of 17 amino acids. The
      sequence also contains a whey-acidic protein (WAP) domain at the C-terminal.
      Transcripts of CruFc were mainly detected in haemocytes and gill by RT-PCR
      analysis. In addition, another full-length cDNA named CshFc was also cloned from
      haemocytes of Chinese shrimp and its inferred amino acid sequence lacks the WAP
      type 'four-disulfide core' domain. The fusion proteins containing CruFc and CshFc
      were, respectively, produced and the antimicrobial assays revealed that the
      recombinant CruFc could inhibit the growth of gram-positive bacteria in vitro but
      the recombinant CshFc could not inhibit at the same conditions. The difference of
      antimicrobial activity between recombinant CruFc and CshFc provides the evidence
      that the four-disulfide core domain of crustin may play an important role in its
      biological function.

PMID- 16987563
TI  - Influenza B viruses isolated in Uruguay during the 2002-2005 seasons: genetic
      relations and vaccine strain match.
AB  - Monitoring antigenic and genetic variations of circulating influenza viruses is
      critical for the selection of annual vaccine strains. In order to gain insight
      into the molecular evolution of Influenza B viruses (IBV) isolated in Uruguay in
      2002 and 2005 outbreaks, antigenic and phylogenetic studies were carried out for
      the Hemagglutinin (HA) gene. Antigenic relations among Uruguayan and reference
      strains isolated elsewhere were performed by means of hemagglutination inhibition
      assays (HAI). Genetic relations of HA genes from Uruguayan as well as 41 IBV
      strains isolated elsewhere were established by means of the construction of
      phylogenetic trees. HAI assays showed a distant antigenic relationship among the
      2002 Uruguayan isolates and the 2002 vaccine strain B/Sichuan/379/99.
      Phylogenetic analysis also revealed a distant genetic relationship among
      Uruguayan and 2002 vaccine strains. All 2005 IBV Uruguayan strains were both
      antigenically and genetically related to B/Victoria lineage-viruses. The results
      of these studies revealed that 2002 IBV Uruguayan strains have a distant
      antigenic and genetic relation with the 2002 IBV vaccine strain used in Uruguay.
      The high rate of susceptible individuals in the youngest cohort (<25 years) might
      be related to the fact that the B/Victoria lineage-viruses were not previously
      circulating in Uruguay.

PMID- 16987564
TI  - Role of preoperative chemotherapy for non-small-cell lung cancer: a meta
      analysis.
AB  - The efficacy of preoperative chemotherapy for improving postoperative survival in
      patients with non-small-cell lung cancer (NSCLC) is controversial. We therefore
      conducted a meta-analysis of the published phase III randomized clinical trials
      (RCTs) to quantitatively evaluate the survival benefit of preoperative
      chemotherapy. After searching the MEDLINE database from 1980 to 2005, five
      studies were selected for the present meta-analysis. DerSimonian-Laird random
      effects analysis was used to estimate the hazard ratio (HR) of patients who
      underwent preoperative chemotherapy at the time points of 1, 3, and 5 years after
      surgery. A total of 564 patients in stages IB-IIIA served as the data sources.
      Preoperative chemotherapy was assigned to a total of 281 patients, while surgery
      alone was assigned to 283 patients. The combined HRs at 1, 3, and 5 years after
      resection were 0.65 (95% CI, 0.45-0.94), 0.83 (95% CI, 0.74-0.93), and 0.85 (95%
      CI, 0.70-1.04), respectively, for preoperative chemotherapy compared to surgery
      alone. The combined survival differences at 1 and 3 years time point were
      significant, while the difference at 5 years after resection was not significant.
      When only the 122 stage IIIA patients were analyzed, none of the HR at any time
      point was significant. In conclusion, the present meta-analysis suggests that the
      benefit of preoperative chemotherapy for patients with NSCLC is unclear,
      especially for stage IIIA patients.

PMID- 16987565
TI  - Challenges to the generality of WBE theory.
AB  - The West, Brown and Enquist (WBE) theory has attracted great interest because it
      makes general predictions about scaling of ecological processes with body size.
      Recent research by Muller-Landau and co-workers challenges the generality of this
      theory by showing that demographic processes in natural forests do not scale in
      the way that the theory predicts. For WBE theory to be relevant to plant
      community dynamics, more complex models are required to deal with the influences
      of competition for light, nutrient supply and disturbance experienced by such
      communities.

PMID- 16987566
TI  - Experimental investigation of pneumatic soil vapor extraction.
AB  - Soil Vapor Extraction (SVE) is a common remediation technique for removing
      volatile organic compounds from unsaturated contaminated soils. Soil
      heterogeneities can however cause serious limitations to the applicability of SVE
      due to air bypassing low permeable areas of the soil, leading to diffusion
      limitation of the remediation. To enhance removal from areas subject to diffusion
      limitation a new remediation technique, pneumatic soil vapor extraction, is
      proposed. In contrast to traditional SVE, in which soil vapor is extracted
      continuously by a vacuum pump, pneumatic SVE is based on enforcing a sequence of
      large pressure drops on the system to enhance the recovery from the low-permeable
      areas. The pneumatic SVE technique was investigated in the laboratory using TCE
      as a model contaminant. 2D-laboratory tank experiments were performed on
      homogeneous and heterogeneous sand packs. The heterogeneous packs consisted of a
      fine sand lens surrounded by a coarser sand matrix. As expected when using
      traditional SVE, the removal of TCE from the low permeable lens was extremely
      slow and subject to diffusion limitation. In contrast when pneumatic venting was
      used removal rates increased by up to 77%. The enhanced removal was hypothesized
      to be attributed to mixing of the contaminated air inside the lens and generation
      of net advective transport out of the lens due to air expansion.

PMID- 16987567
TI  - Plant water status, ethylene evolution, N(2)-fixing efficiency, antioxidant
      activity and lipid peroxidation in Cicer arietinum L. nodules as affected by
      short-term salinization and desalinization.
AB  - Salinity induced changes in ethylene evolution, antioxidant defense system, N(2)
      fixing efficiency and membrane integrity in relation to water and mineral status
      in chickpea (Cicer arietinum L.) nodules were studied under screen house
      conditions. At vegetative stage (55-65 DAS) plants were exposed to single saline
      irrigation (Cl(-) dominated) of levels 0, 2.5, 5.0 and 10.0dSm(-1) and sampled
      after 3d. The other set of treated plants was desalinized by flooding and the
      plants were sampled after further 3d. Water potential (Psiw) of leaf and osmotic
      potential (Psis) of leaf and nodules significantly decreased from -0.44 to 
      0.56MPa and from -0.65 to -1.15MPa and from -0.75 to -1.77MPa, respectively upon
      salinization. RWC of leaf and nodules also reduced from 86.05% to 73.30% and
      94.70% to 89.98%, respectively. The decline in Psis of nodules was due to
      accumulation of proline and total soluble sugar. In comparison to control, the
      increase in ethylene (C(2)H(4)) production was 35-108% higher and correspondingly
      increase in 1-aminocycloprane-1-carboxylic acid (ACC) content (37-126%) and ACC
      oxidase activity (31-118%) was also noticed. Similarly, marked increase in
      H(2)O(2) (25-139%) and thiobarbituric acid substances (TBRAS, 11-133%) contents
      was seen. N(2)-fixing efficiency i.e. N(2)-ase activity, leghemoglobin and N
      contents of nodules declined significantly after saline irrigation. The induction
      in specific activity of antioxidant enzymes was confirmed by the increase in
      activity of superoxide dismutase, peroxidase, ascorbate peroxidase, glutathione
      reductase and glutathione transferase, whereas reverse was true for catalase.
      These activated enzymes could not overcome the accumulation of H(2)O(2) in
      nodules. Ascorbic acid content also declined from 20 to 38%, whereas Na(+)/K(+)
      ratio and Cl(-) content were significantly enhanced. Upon desalinization, a
      partial recovery in all above metabolic processes and water relations parameters
      was noticed. It is suggested that ethylene in relation to water status and lipid
      peroxidation and along with other metabolic processes has an important role in
      induced nodules senescence under salinity.

PMID- 16987568
TI  - Methyl jasmonate is a more effective senescence-promoting factor in Cucurbita
      pepo (zucchini) cotyledons when compared with darkness at the early stage of
      senescence.
AB  - The effects of short-term darkening and methyl jasmonate (MeJA) on cotyledon
      senescence were studied 24h after transfer of intact 7-day-old Cucurbita pepo
      (zucchini) seedlings to darkness or spraying with 100 microM MeJA. The jasmonate
      inhibitory effect on chlorophyll content and chloroplast transcriptional activity
      was stronger compared with darkness. Further, MeJA reduced the photosynthetic
      rate whereas darkness did not affect photosynthesis. Neither stress factor
      affected the photochemical quantum efficiency of photosystem II (PSII) estimated
      by the variable fluorescence (F(v))/maximal fluorescence (F(m)) ratio, suggesting
      the existence of mechanisms protecting the functional activity of PSII at earlier
      stages of senescence, thus making this parameter more stable compared to others
      used to quantify senescence. Both stress factors caused a decrease in the content
      of physiologically active cytokinins, especially trans-zeatin (Z), with the
      jasmonate effect being much more pronounced when compared to darkness. Our
      results indicate that MeJA is a more potent inducer of senescence in zucchini
      cotyledons, at least within the relatively short period of the 24h treatment.
      This is likely due to its stronger down-regulatory effect on the levels of
      physiologically active cytokinins.

PMID- 16987569
TI  - [Topical tacrolimus and resistant skin lesions of dermatomyositis].
AB  - INTRODUCTION: Dermatomyositis is an inflammatory myopathy associated with an
      increased risk of mortality due to visceral involvement. Cutaneous involvement
      has no vital impact but considerably affects the quality of life of the patients
      and can resist to classical therapies. More treatment options are needed. We
      report here the case of three patients presenting resistant cutaneous lesions of
      dermatomyositis successfully treated with topical tacrolimus. OBSERVATIONS: A
      dramatic cure of the lesions of the face and the hands and a moderate response of
      other areas were observed without adverse effects. CONCLUSION: Tacrolimus is an
      immunosuppressive agent and topical tacrolimus is used for the treatment of
      atopic dermatitis and has been occasionally used to treat skin involvement of
      some systemic inflammatory diseases. Topical tacrolimus seems to be a good
      therapeutic alternative for resistant skin lesions of dermatomyositis. It could
      also be proposed as a first intention therapy because of its good tolerance.

PMID- 16987570
TI  - [Behcet's disease in Tunisia. Clinical study of 519 cases].
AB  - PURPOSE: To describe clinical characteristics of Behcet's disease in Tunisia.
      METHODS: It's a retrospective and multicentric study conducted by the Tunisian
      society of internal medicine. Inclusion criteria were those of the international
      study group. Were also included patients without international study group
      criteria but with at least one manifestation among arthritis, venous thrombosis
      or neurological manifestation with oral and genital ulceration or oral ulceration
      and skin lesions. RESULTS: Five hundred and nineteen patients were included.
      87.5% of them fulfilled the international criteria. The male to female ratio was
      2,7. The mean age was 28.7+/-9.3 years at onset and 32.7+/-9.2 years at
      diagnosis. The incidence of each manifestations was as follows: oral ulcers:
      100%, genital ulcers: 87.5%, pseudo-folliculitis: 67.6%, erythema nodosum: 17.5%,
      positive pathergy test: 51%, joint involvement: 55%, uveitis: 32.2%, vein
      thrombosis: 24.9%, arterial aneurysms: 3.9%, neurological involvement: 11.6%. The
      frequency of HLA B51 antigen was 35% among the 187 patients tested. There was no
      difference in the manifestations of the disease between patients having B51 and
      those lacking it. Venous thrombosis (29.8 vs 11.4%), arterial involvement (4.4 vs
      1.4%) and uveitis (37.5 vs 17,9%) were significantly more frequent in men whereas
      erythema nodosum (22.9% vs 15.6%) and joint involvement (70,7 vs 49.9%) more
      frequent in women. The mean follow up was 6,1+/-5.7 years. Mortality rate was
      2.3% in our series. CONCLUSION: Our study confirms the androtropism of the
      disease in Mediterranean and Middle east countries. Positive pathergy test and
      venous thrombosis were more frequent in our study, like those from Mediterranean
      region. Whereas, ocular and neurological involvement were quite less frequent in
      our series.

PMID- 16987571
TI  - [Transient left ventricular apical ballooning syndrome. Case report and review of
      the literature].
AB  - SUBJECT: Transient left ventricular apical ballooning syndrome, known as the
      japanese name of tako-tsubo was recently described and is characterised at the
      acute period by a large apical dyskinesia of the left ventricule apex. This
      syndrome usually mimics an acute coronary syndrome, sometime a cardiac failure or
      arrhythmias. We report a typical case of a seventy-seven years old women struck
      by a tako-tsubo syndrome revealed by an acute chest pain after an emotional
      stress. The diagnosis was proposed because angiography didn't shown any
      abnormality in spite of a large left ventricular dysfunction at the
      ventriculography. Actuality and strong points: Tako-tsubo syndrome is more and
      more published due to a better knowledge of this syndrome, specially in the acute
      coronary syndrome without coronary abnormality. His physiopathology is not well
      known but is clearly in relation with an acute stress. Several hypothesis are
      discussed, helped by some experimental animal model. With an excellent prognosis
      at a middle-course, his discovery allow an adapted take care especially of the
      complications. PROSPECT: The setting up of clinic and electrocardiographic
      reliable and well-tried criteria will allowed an early diagnosis to avoid harmful
      treatment. His specific treatment is not reached by consensus but will develop by
      a better knowledge of the physiopathology.

PMID- 16987572
TI  - Platelet-neutrophil-interactions: linking hemostasis and inflammation.
AB  - Platelets are essential for primary hemostasis, but they also play an important
      pro-inflammatory role. Platelets normally circulate in a quiescent state. Upon
      activation, platelets can secrete and present various molecules, change their
      shape as well as the expression pattern of adhesion molecules. These changes are
      associated with the adhesion of platelets to leukocytes and the vessel wall. The
      interaction of platelets with neutrophils promotes the recruitment of neutrophils
      into inflammatory tissue and thus participates in host defense. This interaction
      of neutrophils with platelets is mainly mediated through P-selectin and beta(2)
      and beta(3) integrins (CD11b/CD18, CD41/CD61). Platelets can also interact with
      endothelial cells and monocytes. Adherent platelets promote the 'secondary
      capture' of neutrophils and other leukocytes. In addition, platelets secrete
      neutrophil and endothelial activators inducing production of inflammatory
      cytokines. Thus, platelets are important amplifiers of acute inflammation.

PMID- 16987573
TI  - Managing US-Mexico "border health": an organizational field approach.
AB  - During World War II Mexican and US health professionals and organizations
      constructed a transnational organizational field to manage the border's public
      health problems. Despite barriers to inter-organizational cooperation, including
      disparate administrative structures and North-South stratification, the field's
      transnational approach to health on the border has continued for 60 years. Using
      archival data to track changes in the number and types of organizations, this
      article argues that the field practitioners call "border health" reconfigured
      during the North American Free Trade Association (NAFTA) decade from an era of
      loosely organized professionals to a specialized bureaucracies era. This change
      brought new vitality to border health, with transnational ties increasing and
      diversifying, but has not weakened entrenched cross-border inequalities. The
      organizational history of the US-Mexico border health field demonstrates how
      macro-politics and inter-organizational stratification shape transnational public
      health problems.

PMID- 16987574
TI  - Stigma, fatigue and social breakdown: exploring the impacts of HIV/AIDS on
      patient and carer well-being in the Caprivi Region, Namibia.
AB  - It is generally assumed that caring is a substantial burden upon households
      afflicted by HIV/AIDS. However, as a 'private' household responsibility, little
      is known about the experiences of either those who provide the care, or those
      receiving care, despite the fact that the process may extend over several years
      and may have a greater impact upon the livelihood security and well-being of the
      household than the actual death of the ill person. Drawing upon data collected
      through solicited diaries, this paper explores how illness and the daily and long
      term duties of caring amongst a sample of households in the Caprivi Region of
      Namibia impacts upon the physical and psychological well-being of ill people and
      their carers. While optimism and enhanced well-being were recorded during periods
      of illness remission, AIDS-related illnesses invariably result in periods of
      sickness and dependency. This results in disempowerment and lowered self-esteem,
      and decreased well-being amongst ill people. This paper argues that the
      increasing dependency of the ill person, widespread pressure to maintain
      household integrity through 'seeing for yourself', i.e. being self-sufficient, or
      at least contributing to reciprocal support networks, and the stigma attached to
      HIV/AIDS can result in considerable intra-household tension and breakdown of key
      social support networks.

PMID- 16987575
TI  - A two generation reproductive toxicity study with curcumin, turmeric yellow, in
      Wistar rats.
AB  - The reproductive toxicity of curcumin, turmeric yellow, in Wistar rats was
      studied in order to generate additional relevant toxicity information for the use
      of curcumin in humans by oral administration. The two generation reproduction
      study was designed and conducted in accordance with OECD Guideline No. 416 [OECD,
      1983. Guidelines for Testing of Chemicals, Guideline No. 416. Two Generation
      Reproduction Toxicity Study, adopted on 26th May 1983] and in compliance with
      Good Laboratory Practices (OECD, 1997 Principles of Good Laboratory Practice for
      the Testing of Chemicals. OECD, C(97)186/Final). The curcumin, mixed in the
      experimental diet at the concentrations of 1500, 3000 and 10,000 ppm was fed to
      three groups of rats, i.e., low, mid and high dose groups, and studied for two
      successive generations. A concurrent control group received experimental diet
      without the curcumin mixture. There were no treatment related adverse
      toxicological effects in the parental animals. No gross or microscopic changes
      were observed in any of the organs. None of the reproductive parameters were
      affected and there were no effects on the offspring other than a small reduction
      in pre-weaning body weight gain of the F2 pups at the highest dose level. It was
      concluded that the no observed adverse effect level (NOAEL) for reproductive
      toxicity of curcumin, fed in the diet for two successive generations to rats in
      this study was 10,000 ppm, which is equivalent to 847 and 959 mg/kg bodyweight
      (bw) per day for male rats and 1043 and 1076 for females for F0 and F1
      generations, respectively. This study was the final toxicology study on curcumin
      reviewed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at the
      61st Meeting, 2003. The JECFA group considered that the small body weight
      reduction in the F2 pups of the highest dose group prevented this from being
      regarded as a no adverse effect level, and so allocated an ADI for curcumin of 0
      3 mg/kg bw based on the intake of 250-320 mg/kg bw in the mid-dose group as the
      NOEL.

PMID- 16987576
TI  - Pentavalent vanadium induces hepatic metallothionein through interleukin-6
      dependent and -independent mechanisms.
AB  - Metallothionein (MT) is a low-molecular-weight cysteine-rich protein which has a
      high affinity for metals. The synthesis of MT is induced by heavy metals such as
      cadmium and zinc. However, little is known about the induction of MT by
      tetravalent or pentavalent metals. We investigated the induction of MT synthesis
      by a pentavalent vanadium compound in mice. Hepatic MT concentrations were
      increased by subcutaneous injection of ammonium metavanadate (AMV) dose
      dependently, and to the similar levels as those induced by zinc chloride.
      However, accumulation of vanadium in the liver was very low, while high
      concentrations of vanadium were detected in the kidney. High performance liquid
      chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS)
      chromatogram of the liver cytosol of AMV-treated mice revealed that the major
      metal bound to MT was not vanadium, but zinc. The chromatogram of the liver
      cytosol of MT null mice demonstrated the existence of a low-molecular-weight
      vanadium-binding protein that is different from MT. A time-course study showed
      that concentrations of serum interleukin-6 (IL-6) and serum amyloid A (SAA), an
      acute-phase protein, increased after the AMV injection. To confirm the
      involvement of IL-6 in MT induction by AMV administration, IL-6 null and wild
      type mice were injected with AMV. In IL-6 null mice, hepatic MT induction by AMV
      administration decreased significantly to about a half of wild-type mice. These
      data suggest that both IL-6-dependent and -independent mechanisms are involved in
      MT induction by vanadium compounds in mice.

PMID- 16987577
TI  - Micro-chemical imaging of cesium distribution in Arabidopsis thaliana plant and
      its interaction with potassium and essential trace elements.
AB  - Cesium as an alkali element exhibits a chemical reactivity similar to that of
      potassium, an essential element for plants. It has been suggested that Cs
      phytotoxicity might be due either to its competition with potassium to enter the
      plant, resulting in K starvation, or to its intracellular competition with K
      binding sites in cells. Such elemental interactions can be evidenced by chemical
      imaging, which determines the elemental distributions. In this study, the model
      plant Arabidopsis thaliana was exposed to 1 mM cesium in the presence (20 mM) or
      not of potassium. The quantitative imaging of Cs and endogenous elements (P, S,
      Cl, K, Ca, Mn, Fe, and Zn) was carried out using ion beam micro-chemical imaging
      with 5 microm spatial resolution. Chemical imaging was also evidenced by
      microfocused synchrotron-based X-ray fluorescence (microXRF) which presents a
      better lateral resolution (<1 microm) but is not quantitative. Cesium
      distribution was similar to potassium which suggests that Cs can compete with K
      binding sites in cells. Cesium and potassium were mainly concentrated in the
      vascular system of stems and leaves. Cs was also found in lower concentration in
      leaves mesophyll/epidermis. This late representing the larger proportion in mass,
      mesophyll/epidermis can be considered as the major storage site for cesium in A.
      thaliana. Trichomes were not found to accumulate cesium. Interestingly, increased
      Mn, Fe, and Zn concentrations were observed in leaves at high chlorosis. Mn and
      Fe increased more in the mesophyll than in veins, whereas zinc increased more in
      veins than in the mesophyll suggesting a tissue specific interaction of Cs with
      these trace elements homeostasis. This study illustrates the sensitivity of ion
      beam microprobe and microfocused synchrotron-based X-ray fluorescence to
      investigate concentrations and distributions of major and trace elements in
      plants. It also shows the suitability of these analytical imaging techniques to
      complement biochemical investigations of metallic stress in plants.

PMID- 16987578
TI  - Adenosine A1 receptor antagonism hastens the decay in ventricular fibrillation
      waveform morphology during porcine cardiac arrest.
AB  - BACKGROUND: Endogenous adenosine (ADO) is known to be cardioprotective during
      acute myocardial ischemia. Coronary sinus ADO concentration has recently been
      shown to increase nearly 13-fold over baseline levels after 5 min of untreated
      ventricular fibrillation (VF). The role of ADO in VF has never been previously
      examined. The objective of this study was to determine the effect of ADO receptor
      antagonism, as measured by the scaling exponent (ScE), on the degeneration of VF
      over time during the circulatory phase of cardiac arrest. METHODS AND RESULTS: A
      well-established swine model of prolonged VF arrest was used for this experiment.
      Eighteen domestic mixed-breed swine were assigned by block randomization to
      receive either DTI-0017 (5mg/kg), a potent ADO A(1) receptor antagonist or
      placebo in a double-blind fashion. The animals were instrumented under general
      anesthesia and acclimatized. The assigned solution was infused over 5 min. One
      minute after the infusion was completed, VF was induced with a 3s, 60 Hz, 100 mA
      transthoracic shock and left untreated. Lead II ECG was monitored continuously
      and recorded at 1000 samples/s. It was determined a priori that evaluation of the
      plots would be limited to a previously observed plateau phase historically
      occurring between 5 and 8 min corresponding to the circulatory phase of cardiac
      arrest. The scaling exponent values over this period were calculated for each of
      the 18 recordings using custom MATLAB routines. Using the Wald statistic to
      produce the Chi square distributions the null hypothesis, that there was no
      difference between the two groups, was tested. The Wald statistic calculation
      based on eight epochs from 300 to 475 s in placebo and DTI groups was significant
      to reject the null hypothesis of no difference in the groupxtime interaction at
      the 0.015 level (Chi square distribution for Wald=17.49, d.f.=7). CONCLUSIONS: In
      this swine model, adenosine A(1) receptor antagonism accelerated the natural
      decay in the ECG VF waveform during the circulatory phase of cardiac arrest. Our
      findings would suggest that endogenous adenosine has cardioprotective effects
      during sudden cardiac arrest by slowing the time-dependent degeneration of VF.

PMID- 16987579
TI  - Colon ischaemia and necrosis as a complication of prolonged but successful CPR.
AB  - Survival after prolonged cardiopulmonary resuscitation (CPR) is often associated
      with neurological and other sequelae. We describe a patient who survived
      prolonged cardiac arrest due to ventricular fibrillation neurologically intact
      but suffered colon ischaemia and necrosis in the post-resuscitation period.
      Subtotal colectomy was performed. We wonder whether this complication was related
      to the use of vasopressin.

PMID- 16987580
TI  - The demand for prehospital advanced life support and the appropriateness of
      dispatch in Taipei.
AB  - INTRODUCTION: Implementing prehospital advanced life support (ALS) services
      requires more medical and societal resources in training and equipment. The
      actual demand for ALS services in our communities was not clear. To ensure good
      use of expensive resources, it is important to evaluate the demand and
      appropriateness of ALS services before full-scale implementation takes place.
      OBJECTIVE: To evaluate the rate and characteristics of demand for ALS, and the
      appropriateness of ALS dispatch of the emergency medical service (EMS) system in
      metropolitan Taipei City. METHODS: A retrospective, cross-sectional analysis of
      the EMS records of Taipei City Fire Department from April 1999 to December 2000
      was conducted. Stratified random sampling of all EMS records in the second week
      of January, April, July and October of 2000 were obtained, along with the
      corresponding ALS dispatch records. Retrospective ALS demand criteria, including
      the chief complaints, mechanisms of injury/illness, initial vital signs and types
      of care rendered, were developed to estimate the rate of ALS demand. ALS demand
      is expressed as the percentage of cases fulfilling ALS criteria over the total
      number of EMS cases. Appropriate ALS dispatches were those ALS dispatches
      determined as fulfilling the ALS demand criteria. RESULTS: Among the sampled 5433
      EMS cases, 490 (9.02%) were determined as a demand for ALS care. ALS demands
      varied from region to region, and were higher during winter months and afternoon
      rush hours. There were 175 actual ALS dispatches, accounting for 3.22% of the
      sampled EMS services. The triage performance was suboptimal: the appropriateness
      of ALS dispatch was 37.14%; the overtriage rate was 72.86%. CONCLUSION: Around
      nine percent of EMS calls demand ALS services. The current triage performance for
      proper ALS dispatch was suboptimal. A correct ALS dispatch protocol and more
      dispatcher training programmes should be established in the communities to ensure
      best use of valuable ALS resources.

PMID- 16987581
TI  - Survival in cancer patients undergoing in-hospital cardiopulmonary resuscitation:
      a meta-analysis.
AB  - INTRODUCTION: Cardiopulmonary resuscitation is thought to be a low-yield
      intervention in cancer patients. In patients with metastatic disease the
      procedure is thought to be futile. Comprehensive data on survival to discharge in
      subsets of cancer patients undergoing in-hospital cardiopulmonary resuscitation,
      however, are lacking. OBJECTIVE: To determine the rate of survival to discharge
      for adult cancer patients undergoing in-hospital cardiopulmonary resuscitation.
      METHOD: A systematic search of MEDLINE and our primary sources' references was
      performed for studies involving in-hospital cardiac arrest, in clearly defined
      subsets of adult cancer patients, with outcomes that included survival to
      hospital discharge. RESULTS: Forty-two studies from 1966-2005, comprising 1707
      patients met our minimal inclusion criteria. Overall survival to discharge was
      6.2%. Survival in patients with localized disease was 9.5%, and in patients with
      metastatic disease was 5.6%. Analysis of data reported since 1990 reveals a
      narrowing of the survival gap, with survival rates in patients with localised
      disease of 9.1%, and in patients with metastatic disease of 7.8%. Survival in
      patients resuscitated on the general medical/surgical wards was 10.1%, while
      survival in patients resuscitated on intensive care units (ICUs) was 2.2%.
      CONCLUSIONS: Overall survival of CPR to hospital discharge in cancer patients
      compares favorably to survival rates in unselected inpatients. Improved outcomes
      in recent years in patients with metastatic disease are likely to reflect more
      selective use of CPR in cancer patients, with the sickest patients deselected.

PMID- 16987582
TI  - Eighth grade students become proficient at CPR and use of an AED following a
      condensed training programme.
AB  - OBJECTIVE: To evaluate a new, 1-h, condensed training programme to teach
      continuous chest compression cardiopulmonary resuscitation (CCC-CPR) and
      automated external defibrillator (AED) skills to a cohort of eight grade public
      school students. METHODS:  RESULTS: Thirty-three eligible subjects completed the
      programme; mean age 13.7 years; 48.5% female. Eight participants reported some
      prior training in CPR and AED use. Following initial training, 29/33 (87.8%)
      subjects demonstrated proficiency at CCC-CPR and AED application/operation in a
      mock adult cardiac arrest scenario. At four-weeks, 28/33 (84.8%) subjects
      demonstrated skill retention in similar scenario testing. Subjects also showed
      improvement in written knowledge regarding AED use as shown by scores on an AHA
      based written exam (60.9% versus 77.3%; p<0.001). CONCLUSION: With our focused,
      condensed training program, eighth grade public school students became proficient
      in CCC-CPR and AED use. This is the first study to document the ability of middle
      school students to learn and retain CCC-CPR and AED skills for adult sudden
      cardiac arrest victims with such a curriculum.

PMID- 16987583
TI  - A randomized controlled trial of efficacy and ST change following use of the
      Welch-Allyn MRL PIC biphasic waveform versus damped sine monophasic waveform for
      external DC cardioversion.
AB  - OBJECTIVE: Biphasic waveforms have similar or greater efficacy at cardioverting
      atrial and ventricular arrhythmias at lower energy levels than monophasic
      waveforms, and cause less ST depression following defibrillation of ventricular
      fibrillation. No studies have investigated this effect on ST change with atrial
      arrhythmias. We studied the efficacy of the Welch Allyn-MRL PIC biphasic
      defibrillator. METHODS: One hundred and thirty-nine patients undergoing elective
      DC cardioversion for atrial arrhythmias were randomised to cardioversion by
      monophasic (Hewlett Packard Codemaster XL; 100, 200, 300, 360 and 360J) or
      biphasic (Welch Allyn-MRL PIC; 70, 100, 150, 200 and 300J) defibrillator. We
      analysed success of cardioversion after 0 and 30min, cumulative energy, number of
      shocks and energy at successful cardioversion. The ST change in the recorded
      electrocardiogram was measured at 15s after all shocks using electronic
      callipers. RESULTS: Immediately after cardioversion 59/68 (86.8%) of the
      monophasic group versus 56/60 (93.3%) of the biphasic group were in sinus rhythm.
      Of the monophasic group, 55/67 (82.1%) remained in sinus rhythm at 30min versus
      53/58 (91.4%) of the biphasic group. These differences were not significant at
      0min (P=0.35) or 30min (P=0.21). The biphasic group required significantly fewer
      shocks (P=0.006), less cumulative energy (P<0.0001) and required lower total
      energy for successful cardioversion (P<0.0001). Of the 102 patients with
      electrocardiogram recordings suitable for analysis, ST segment change was greater
      in the monophasic group (P=0.037). CONCLUSIONS: The Welch Allyn-MRL biphasic
      waveform for DC cardioversion results in fewer shocks, with less cumulative
      energy delivered and less post shock ST change than with a Hewlett Packard
      Codemaster XL damped sine wave monophasic waveform.

PMID- 16987584
TI  - What is the appropriate outcome for studies of treatments for out-of-hospital
      cardiac arrest?
AB  - BACKGROUND: A good outcome following out-of-hospital medical care for cardiac
      arrest is survival to hospital discharge. Because a large number of patients are
      required to detect a minimum clinically important difference in survival, an
      intermediate outcome such as hospital admittance is commonly used. For an
      intermediate outcome to be a useful surrogate, the survival rate conditional on
      achieving the intermediate outcome should not depend upon the field treatment. If
      so, an advantage of the intermediate outcome may be a smaller sample size.
      However, recent trials demonstrate that survival conditional on admittance may
      depend upon the field treatment. Even if the resources are available to power a
      study for survival, is survival the right outcome? For example, no increase in
      survival and a large increase in admittance could be considered a bad result, as
      it represents a substantial waste of resources. Similarly no increase in
      mortality and a decrease in admittance should be considered a good result, as it
      represents a substantial cost savings without any sacrifice of life. Both
      admittance and survival are important outcomes and need to be considered jointly,
      that is, as a bivariate outcome. METHODS: Cost-effectiveness concepts are used to
      distinguish between a good and bad (bivariate) outcome. Simulations are conducted
      to compare the impact of the univariate and the bivariate outcomes in a variety
      of trial scenarios. A table of sample sizes is computed for the bivariate outcome
      across a range of trial scenarios. RESULTS: The bivariate outcome outperforms
      both univariate outcomes for most alternatives. The required sample size for the
      joint outcome of admittance and survival may be substantially, over 50%, less
      than that for the survival outcome alone. CONCLUSION: Use of the bivariate
      outcome could provide more informed decision making about resuscitation
      strategies and at less cost then the current gold standard of hospital survival.

PMID- 16987585
TI  - Outcome of cardiopulmonary resuscitation in a 2300-bed hospital in a developing
      country.
AB  - OBJECTIVE: To evaluate the outcome and quality of in-hospital cardiopulmonary
      resuscitation (CPR), and factors affecting the outcome. SETTING: A 2300-bed
      university hospital in Thailand. METHOD: A 1-year prospective audit according to
      the Utstein style. RESULTS: A total of 639 cardiac arrests (370 male, 269 female,
      age 1 day-96 years, mean+/-S.D.=53.3+/-24.12 years) were included. Four hundred
      and thirty-three cardiac arrests (67.8%) occurred in non-monitored areas and 200
      (31.3%) occurred in monitored areas. Five hundred and thirty-six cardiac arrests
      (84%) were witnessed. The majority of cardiac arrests occurred in medical
      patients (68.4%) and surgical patients (21.4%). The most common underlying causes
      of arrest were respiratory failure (24.7%) and septic shock (23.3%). Initial ECG
      rhythms were ventricular fibrillation 79 (12.4%), asystole 272 (42.6%) with
      pulseless electrical activity 225 (35.2%). Most patients received basic life
      support within 1 min (86.7%) and advanced life support (ALS) within 4 min (92.6%)
      but only 25% of patients received defibrillation within 3 min. Following
      resuscitation, 394 (61.7%) achieved restoration of spontaneous circulation and 44
      patients (6.9%) survived to discharge. Only 162 post-arrest patients were treated
      in the critical care area. The initial survival rate was not associated with sex,
      age and time to ALS, but was significantly related to the monitored area.
      CONCLUSION: In our setting, survival to discharge is 6.9%. Initial survival rate
      was strongly associated with being in a monitored area. Defibrillators and the
      critical care areas were insufficient.

PMID- 16987586
TI  - Clinical testing of cellular phone ringing interference with automated external
      defibrillators.
AB  - OBJECTIVE: This study examined cellular phone ringing interference with automated
      external defibrillators (AED). METHODS: The phone systems tested were two single
      band handheld telephones: (1) a Global System for Mobile Communication (GSM)
      receiver; and (2) a Personal Communication Services (PCS) receiver. The ringing
      phase of a digital cellular phone includes a brief burst of peak-emitted power.
      The GSM had a maximum power output of 2 W, operating on a 900 MHz carrier
      frequency, and the PCS had a maximum output of 1 W, operating on a 1800 MHz
      carrier frequency. During AED monitoring, the digital cellular telephone was
      placed successively in three positions: (1) on the AED; (2) on the patient's
      chest between the electrodes; and (3) on the connector between the electrodes and
      the AED cable. After positioning the cellular phone, calls were placed during the
      AED analyzing phase. RESULTS: Three AED models were tested using their original
      electrodes: (1) LifePak 20 monitor/defibrillator device; (2) Lifepak 20 P
      monitor/defibrillator/stimulator (Medtronic Emergency Response Systems, Redmond,
      WA, USA); and (3) HeartStart XL M4735A monitor/defibrillator (Philips Medical
      Systems, Andover, MA, USA). The first two devices had Quik-Combo electrodes and
      the third device had Adults Plus multifunction electrodes. Ninety-one tests were
      performed on 13 patients. The only disturbance provoked by testing was noise
      emitted by the AED speaker when the receiver was close to the device. The noise
      began 2-4 s before the first audible ringing tone and persisted throughout the
      ringing phase. The distance at which this effect could be prevented was 15 cm.
      CONCLUSION: Clinical testing during ECG monitoring by an AED during call from a
      cellular phone did not show any analysis dysfunction during unshockable rhythms
      and provoked only transient dysfunction of the speaker device.

PMID- 16987587
TI  - Comparison of three simulation-based training methods for management of medical
      emergencies.
AB  - Trainee medical officers (TMOs) participated in a study comparing three methods
      of simulation-based training to treat medical emergencies occurring in a hospital
      setting. The methods were: All groups had the same total teaching time.
      Participants (n=61) had an initial (pre-training) assessment by written tests,
      self assessment and simulations of medical emergencies ('VT' and
      'HYPOglycaemia'). Participants were tested again post-training using similar
      simulations to the initial scenario and a new scenario ('ANAphylaxis'). Trained
      'experts', blinded to the teaching group of participants, watched video-CDs of
      the simulations to assess participants' performance. All groups demonstrated
      increased knowledge and confidence (pre-training scores compared to post
      training) but no differences could be detected between the three groups. In
      simulated emergencies, post-training scores were also improved. There was no
      difference between groups in the 'HYPO' scenario but in the 'VT' scenario there
      was moderate evidence that Group 3 was superior. In the 'ANA' scenario, Group 3
      had far better test scores, especially in behavioural items. There did not appear
      to be any significant advantage of using whole body manikins over CSBT and simple
      part-task trainers. Full-mission simulation training helped develop the ability
      to recognise when skills learnt to manage one type of medical emergency can be
      useful in managing another emergency not previously encountered.

PMID- 16987588
TI  - Aortic dissection.

PMID- 16987589
TI  - Microvascular blood flow during cardiopulmonary resuscitation is predictive of
      outcome.
AB  - There is growing evidence that microcirculatory blood flow is the ultimate
      determinant of the outcome in circulatory shock states. We therefore examined
      changes in the microcirculation accompanying the most severe form of circulatory
      failure, namely cardiac arrest and the effects of subsequent cardiopulmonary
      resuscitation. Ventricular fibrillation was electrically induced in nine pigs and
      untreated for 5min prior to beginning closed chest cardiac compression and
      attempting electrical defibrillation. Orthogonal polarization spectral imaging
      was utilized for visualization of the sublingual microcirculation at baseline,
      0.5, 1, 3 and 5min after onset of ventricular fibrillation and at 1 and 5min
      after start of chest compression. Images were also obtained 1 and 5min after
      restoration of spontaneous circulation. Microvascular flow was graded from 0 (no
      flow) to 3 (normal flow). Aortic and right atrial pressures were measured and
      coronary perfusion pressure was computed continuously. Microcirculatory blood
      flow decreased to less than one-fourth within 0.5min after inducing ventricular
      fibrillation. Precordial compression partially restored microvascular flow in
      each animal. In animals that were successfully resuscitated, microvascular flow
      was significantly greater after 1 and 5min of chest compression than in animals
      with failed resuscitation attempts. Microvascular blood flow was highly
      correlated with coronary perfusion pressure (r=0.82, p<0.01). Microvascular blood
      flow in the sublingual mucosa is therefore closely related to coronary perfusion
      pressure during cardiopulmonary resuscitation and both are predictive of outcome.

PMID- 16987590
TI  - Assessment of neonatal resuscitation skills: a reliable and valid scoring system.
AB  - OBJECTIVE: To study the reliability and validity of a scoring instrument for the
      assessment of neonatal resuscitation skills in a training setting. METHODS:
      Fourteen paediatric residents performed a neonatal resuscitation on a manikin,
      while being recorded with a video camera. The videotapes were analysed using an
      existing scoring instrument with an established face and content validity,
      adjusted for use in a training setting. Intra- and inter-rater reliability were
      assessed by comparing the ratings of the videotapes of three raters, one of who
      rated the videotapes twice. Intra-class coefficients (ICC) were calculated for
      the sum score, percentages of agreement and kappa coefficients for the individual
      items. To study construct validity, the performance of a second resuscitation of
      by residents was assessed after they had received feedback on their first
      performance. RESULTS: The ICC were 0.95 and 0.77 for intra- and inter-rater
      reliability, respectively. The median percentage of intra-rater agreement was
      100%; inter-rater agreement 78.6-84.0%. The median kappa was 0.85 for intra-rater
      reliability, and 0.42-0.59 for inter-rater reliability. Residents showed a 10%
      improvement (95% confidence interval -4; 23%) on performance of a second
      resuscitation, which supports the instrument's construct validity. CONCLUSION: A
      useful and valid instrument with good intra-rater and reasonable inter-rater
      reliability is now available for the assessment of neonatal resuscitation skills
      in a training setting. Its reliability can be improved by using a more advanced
      manikin and by training of the raters.

PMID- 16987591
TI  - Crystallographic investigation of the dried exudate of the major vestibular
      (Bartholin's) glands in women.
AB  - OBJECTIVE: The aim of this study was to investigate the dried secretion of human
      major vestibular glands in order to establish its crystallographic pattern and to
      compare the data with those obtained for other human genital biopolymers. STUDY
      DESIGN: After air drying, samples were examined comparatively under transmitted
      and polarized light. At first sight, dehydrated vestibular fluid exhibits a fern
      like crystallographic pattern very similar in appearance to those described in
      mid-cycle cervical mucus and bulbo-urethral fluid. RESULTS: Dendritic structures
      fill the central space of all preparations, prolonged by apparently amorphous
      peripheral fucus-like expansions. Spherulitic interdendritic crystalline
      microstructures (ICMs) can be considered a constant feature of dried vestibular
      exudate. In contrast with dendritic formations, fucus-like expansions and
      isolated spherulites are anisotropic under polarized light. Anisotropy appears to
      be the guise of a luminescent border lining the dendrites or bright nodules
      shining on a dark background. CONCLUSION: The study confirms the close physico
      chemical proximity of vestibular secretion, mid-cycle cervical mucus and bulbo
      urethral fluid. However, if isotropic dendritic formations and anisotropic
      structures are grossly similar, the number and size of the anisotropic ICMs are
      typical of human vestibular secretion. The different patterns of ICMs observed in
      these three human biological hydrogels demonstrate differences in the salt
      concentrations.

PMID- 16987592
TI  - Manipulation of small-molecule inhibitory kinetics modulates MCH-R1 function.
AB  - The capacity of novel benzopyridazinone-based antagonists to inhibit MCH-R1
      function, relative to their affinity for the receptor, has been investigated.
      Three compounds that differ by the addition of either a chlorine atom, or
      trifluoromethyl group, have nearly identical receptor affinities; however their
      abilities to inhibit receptor elicited signaling events, measured as a function
      of time, are dramatically altered. Both the chlorinated and trifluoromethyl
      modified compounds have a very slow on-rate to maximal functional inhibition
      relative to the unmodified base compound. A similar impact on inhibitory capacity
      can be achieved by modifying the side-chain composition at position 2.53 of the
      receptor; replacement of the native phenylalanine with alanine significantly
      reduces the amount of time required by the chlorinated compound to attain maximal
      functional inhibition. The primary attribute responsible for this alteration in
      inhibitory capacity appears to be the overall bulk of the amino acid at this
      position-substitution of the similarly sized amino acids leucine and tyrosine
      results in phenotypes that are indistinguishable from the wild type receptor.
      Finally, the impact of these differential inhibitory kinetics has been examined
      in cultured rat neurons by measuring the ability of the compounds to reverse MCH
      mediated inhibition of calcium currents. As observed using the cell expression
      models, the chlorinated compound has a diminished capacity to interfere with
      receptor function. Collectively, these data suggest that differential inhibitory
      on rates between a small-molecule antagonist and its target receptor can impact
      the ability of the compound to modify the biological response(s) elicited by the
      receptor.

PMID- 16987593
TI  - Another opinion on the appearance of pseudocysts.

PMID- 16987594
TI  - Non-thermal plasma-induced photocatalytic degradation of 4-chlorophenol in water.
AB  - TiO(2) photocatalyst (P-25) (50mgL(-1)) was tentatively introduced into pulsed
      high-voltage discharge process for non-thermal plasma-induced photocatalytic
      degradation of the representative mode organic pollutant parachlorophenol (4-CP),
      including other compounds phenol and methyl red in water. The experimental
      results showed that rate constant of 4-CP degradation, energy efficiency for 4-CP
      removal and TOC removal with TiO(2) were obviously increased. Pulsed high-voltage
      discharge process with TiO(2) had a promoted effect for the degradation of these
      pollutants under a broad range of liquid conductivity. Furthermore, the apparent
      formation rates of chemically active species (e.g., ozone and hydrogen peroxide)
      were increased, the hydrogen peroxide formation rate from 1.10x10(-6) to 1.50x10(
      6)Ms(-1), the ozone formation rate from 1.99x10(-8) to 2.35x10(-8)Ms(-1),
      respectively. In addition, this process had no influence on the photocatalytic
      properties of TiO(2). The introduction of TiO(2) photocatalyst into pulsed
      discharge plasma process in the utilizing of ultraviolet radiation and electric
      field in pulsed discharge plasma process enhanced the yields of chemically active
      species, which were available for highly efficient removal and mineralization of
      organic pollutants.

PMID- 16987595
TI  - Reduction of chromate from electroplating wastewater from pH 1 to 2 using
      fluidized zero valent iron process.
AB  - Fluidized zero valent iron (ZVI) process was conducted to reduce hexavalent
      chromium (chromate, CrO(4)(2-)) to trivalent chromium (Cr(3+)) from
      electroplating wastewater due to the following reasons: (1) Extremely low pH (1
      2) for the electroplating wastewater favoring the ZVI reaction. (2) The ferric
      ion, produced from the reaction of Cr(VI) and ZVI, can act as a coagulant to
      assist the precipitation of Cr(OH)(3(s)) to save the coagulant cost. (3) Higher
      ZVI utilization for fluidized process due to abrasive motion of the ZVI. For
      influent chromate concentration of 418 mg/L as Cr(6+), pH 2 and ZVI dosage of 3g
      (41 g/L), chromate removal was only 29% with hydraulic detention time (HRT) of
      1.2 min, but was increased to 99.9% by either increasing HRT to 5.6 min or
      adjusting pH to 1.5. For iron species at pH 2 and HRT of 1.2 min, Fe(3+) was more
      thermodynamically stable since oxidizing agent chromate was present. However, if
      pH was adjusted to 1.5 or 1, where chromate was completely removed, high Fe(2+)
      but very low Fe(3+) was present. It can be explained that ZVI reacted with
      chromate to produce Fe(2+) first and the presence of chromate would keep
      converting Fe(2+) to Fe(3+). Therefore, Fe(2+) is an indicator for complete
      reduction from Cr(VI) to Cr(III). X-ray diffraction (XRD) was conducted to exam
      the remained species at pH 2. ZVI, iron oxide and iron sulfide were observed,
      indicating the formation of iron oxide or iron sulfide could stop the chromate
      reduction reaction.

PMID- 16987596
TI  - Enhanced desorption and biodegradation of phenanthrene in soil-water systems with
      the presence of anionic-nonionic mixed surfactants.
AB  - The effects of anionic-nonionic mixed surfactants, sodium dodecyl sulfate (SDS)
      mixed with Triton X-100 (TX100), on the desorption and biodegradation of
      phenanthrene in soil-water system were investigated in an aim to improve the
      efficiency of surfactant bioremediation technology. Results indicated that the
      presence of SDS not only increased the solubilization of TX100 for phenanthrene,
      but also reduced the sorption of TX100 onto soils. As a result, the desorption
      efficiency of phenanthrene from the contaminated soil was greatly enhanced by
      mixed surfactant solutions compared with that by single TX100 solution and
      appeared to be positively related with the mole fraction of SDS in solution.
      Mixed surfactants with relatively smaller ratio promoted phenanthrene
      biodegradation, for example, the biodegradation percentage of phenanthrene in 1:9
      SDS-TX100 mixed solutions was about 165% of that in the single TX100 solution at
      the same TX100 concentration of 1.6 mmol/L in 24h. But the biodegradation was
      inhibited with larger ratio of SDS in the mixed solutions, which may be due to
      the preferential utilization of SDS by phenanthrene degraders. Thus, the
      selection of mixed surfactants should consider simultaneously the effects of SDS
      on desorption and biodegradation. The experimental results can be used to provide
      valuable information in designing the surfactant bioremediation technology for
      contaminated soils.

PMID- 16987597
TI  - On the distribution and bonding environment of Zn and Fe in glasses containing
      electric arc furnace dust: a mu-XAFS and mu-XRF study.
AB  - We apply synchrotron radiation assisted X-ray fluorescence (SR-XRF), SR-XRF
      mapping as well as micro- and conventional X-ray absorption fine structure (mu
      XAFS and XAFS) spectroscopies in order to study the bonding environment of Fe and
      Zn in vitrified samples that contain electric arc furnace dust from metal
      processing industries. The samples are studied in the as-cast state as well as
      after annealing at 900 degrees C. The SR-XRF results demonstrate that annealing
      does not induce any significant changes in the distribution of either Fe or Zn,
      in both the as-cast and annealed glasses. The mu-XAFS spectra recorded at the Fe
      K and Zn-K edges reveal that the structural role of both Fe and Zn remains
      unaffected by the annealing procedure. More specifically, Fe forms both FeO(6)
      and FeO(4) polyhedra, i.e. acts as an intermediate oxide while Zn occupies
      tetrahedral sites.

PMID- 16987598
TI  - Heterogeneous photocatalysed degradation of 4-chlorophenoxyacetic acid in aqueous
      suspensions.
AB  - The photocatalysed degradation of 4-chlorophenoxyacetic acid (4-CPA, 1) has been
      investigated in aqueous suspensions of titanium dioxide under a variety of
      conditions. The degradation was studied by monitoring the change in substrate
      concentration employing UV spectroscopic analysis technique and depletion in
      total organic carbon (TOC) content as a function of irradiation time. The
      influence of various parameters such as, different types of titanium dioxide
      (TiO2) powders, pH, catalyst and substrate concentrations, and in the presence of
      electron acceptor such as hydrogen peroxide (H(2)O(2)) besides molecular oxygen
      has been investigated. The effects of these parameters on the degradation rates
      were found to be significant. The volatile degradation product 4-chlorophenol was
      analyzed by GC-MS technique and probable pathways for the formation of product
      has been proposed.

PMID- 16987599
TI  - Removal of boron from aqueous solution by using neutralized red mud.
AB  - The adsorptive removal of boron from aqueous solution by using the neutralized
      red mud was studied in batch equilibration technique. The effects of pH,
      adsorbent dosage, initial boron concentration and contact time on the adsorption
      were investigated. The experiments demonstrated that boron removal was of a
      little fluctuation in pH range of 2-7 and it takes 20 min to attain equilibrium.
      The adsorption data was analyzed using the Langmuir and the Freundlich isotherm
      models and it was found that the Freundlich isotherm model represented the
      measured sorption data well.

PMID- 16987600
TI  - Effect of acclimatization of microorganisms to heavy metals on the performance of
      activated sludge process.
AB  - Although selected heavy metals (HMs) stimulate biological reactions at low
      concentrations, all HMs are toxic to microorganisms (MOs) at moderate
      concentrations and can cause inhibitory effects on the biological processes.
      Therefore, MOs must be acclimated to HMs or other toxic substances present in
      wastewaters (WWs) before they are used in an activated sludge process (ASP). In
      this study, combined effect of Cu(2+) and Zn(2+) ions in a synthetic WW on the
      efficiency of a laboratory-scale ASP without recycle was investigated using
      acclimated MOs at different extents.A synthetic feed solution of 1222 mg L(-1)
      proteose-peptone (corresponding to 1300 mg COD L(-1)) served as a source of
      carbon. Cu(2+) and Zn(2+) ions at different concentrations (1.5, 4.5 and 9, 27 mg
      L(-1), respectively) were introduced in the feed to a continuously stirred
      activated sludge reactor at different hydraulic residence times (2-40 h) keeping
      pH, temperature and stock feed composition constant. The combined effects of
      copper and zinc ions were determined by mixing these metallic ions at the
      specified combinations of concentrations such as "1.5 mg L(-1) of Cu(2+)+9 mg L(
      1) of Zn(2+)" and "4.5 mg L(-1) of Cu(2+)+27 mg L(-1) of Zn(2+)". It was observed
      that using seed MOs acclimatized to two times of the combined threshold
      concentration of these HMs for an unduly long period of time (1-4 months) caused
      adverse effects on the ASP performance. Besides, it was found that usual
      inhibition effects of these HMs were enhanced with increasing period of
      acclimation. Substantially lower substrate removal efficiencies were obtained
      with acclimatized MOs than those obtained with non-acclimatized MOs. At the
      higher initial substrate concentration of 2500 mg COD L(-1), substrate-inhibition
      occurred causing a decrease in the specific growth rate constant (k); however, HM
      inhibition was suppressed, resulting to about 20% increase in treatment
      efficiency of the ASP. It can be concluded that the time period necessary for
      acclimatization of seed MOs must be adjusted carefully with concentrations of HMs
      lower than their threshold concentrations to achieve an optimal operation of an
      aerobic biological process.

PMID- 16987601
TI  - Surfactant-enhanced electrokinetic removal of phenanthrene from kaolinite.
AB  - Removal of hydrophobic organic contaminants (HOCs) using surfactant-enhanced
      electrokinetic (EK) method was studied in a model system. Kaolinite and
      phenanthrene were selected as a model clay soil and a representative HOC,
      respectively. Three different types of surfactants: APG (alkyl polyglucoside),
      Brij30 (polyoxyethylene-4-lauryl ether), and SDS (sodium dodecyl sulfate), were
      used to enhance the solubility of HOC. Characteristics of surfactants, such as
      surface tension, HOC solubility, and biodegradability were measured. In the case
      of Brij30 solution, phenanthrene solubility was higher than that of others. After
      4 days, APG and Brij30 were degraded by 65% and 26% of the initial amount,
      respectively. However, degradation of SDS was hardly detected. Electroosmotic
      flow (EOF) of Brij30 solution was lower than others when the 0.1M NaCl was used
      as electrolyte. Addition of the acetate buffer solution increased the EOF of
      Brij30 solution and enhanced removal of phenanthrene. Among three different
      surfactants tested, APG showed the highest removal efficiency.

PMID- 16987602
TI  - Evaluation of Fuller's earth for the adsorption of mercury from aqueous
      solutions: a comparative study with activated carbon.
AB  - Fuller's earth (FE) has been used as an adsorbent in this work to remove mercury
      from aqueous solutions. For the purpose of comparison, simultaneous experiments
      using activated carbon (AC) have also been done. The aim of the work is to test
      how best FE can be used as an adsorbent for mercury. Equilibrium isotherms, such
      as Freundlich, Langmuir, Dubinin-Redushkevich, Temkin, Harkins-Jura, Halsey and
      Henderson have been tested. Kinetic studies based on Lagergren first-order,
      pseudo-second-order rate expressions and intra-particle diffusion studies have
      been done. The batch experiments were conducted at room temperature (30 degrees
      C) and at the normal pH (6.7+/-0.2) of the solution. It has been observed that
      Hg(II) removal rate is better for FE than AC, due to large dosage requirement,
      whereas the adsorption capacity of AC is found to be much better than FE. Hence,
      although FE can be used as an adsorbent, a high dosage is required, when compared
      to AC. Hybrid fractional error function analysis shows that the best-fit for the
      adsorption equilibrium data is represented by Freundlich isotherm. Kinetic and
      film diffusion studies show that the adsorption of mercury on FE and AC is both
      intra-particle diffusion and film diffusion controlled.

PMID- 16987603
TI  - Innovative physico-chemical treatment of wastewater incorporating Moringa
      oleifera seed coagulant.
AB  - Moringa oleifera is a pan tropical, multipurpose tree whose seeds contain a high
      quality edible oil (up to 40% by weight) and water soluble proteins that act as
      effective coagulants for water and wastewater treatment. The use of this natural
      coagulant material has not yet realised its potential. A water extract of M.
      oleifera seed was applied to a wastewater treatment sequence comprising
      coagulation-flocculation-sedimentation-sand filtration. The study was laboratory
      based using an actual wastewater. Overall COD removals of 50% were achieved at
      both 50 and 100mg/l M. oleifera doses. When 50 and 100mg/l seed doses were
      applied in combination with 10mg/l of alum, COD removal increased to 58 and 64%,
      respectively. The majority of COD removal occurred during the filtration process.
      In the tests incorporating alum, sludge generation and filter head loss increased
      by factors of 3 and 2, respectively. These encouraging treatment results indicate
      that this may be the first treatment application that can move to large scale
      adoption. The simple water extract may be obtained at minimal cost from the
      presscake residue remaining after oil extraction from the seed. The regulatory
      compliance issues of adopting 'new materials' for wastewater treatment are
      significantly less stringent than those applying to the production of potable
      water.

PMID- 16987604
TI  - Removal of lead from aqueous solution using Syzygium cumini L.: equilibrium and
      kinetic studies.
AB  - The biosorption of lead ions from aqueous solution by Syzygium cumini L. was
      studied in a batch adsorption system as a function of pH, contact time, lead ion
      concentration, adsorbent concentration and adsorbent size. The biosorption
      capacities and rates of lead ions onto S. cumini L. were evaluated. The Langmuir,
      Freundlich, Redlich-Peterson and Temkin adsorption models were applied to
      describe the isotherms and isotherm constants. Biosorption isothermal data could
      be well interpreted by the Langmuir model followed by Temkin model with maximum
      adsorption capacity of 32.47 mg/g of lead ion on S. cumini L. leaves biomass. The
      kinetic experimental data were properly correlated with the second-order kinetic
      model.

PMID- 16987605
TI  - Chemical mass balance source apportionment of PM10 and TSP in residential and
      industrial sites of an urban region of Kolkata, India.
AB  - Daily average PM(10) (particulate matter which passes through a size selective
      impactor inlet with a 50% efficiency cut-off at 10 microm aerodynamic diameter),
      TSP (total suspended particulate matter) and their chemical species mass
      concentrations were measured at residential and industrial sites of an urban
      region of Kolkata during November 2003-November 2004. Source apportionment using
      chemical mass balance model revealed that the most dominant source throughout the
      study period at residential site was coal combustion (42%), while vehicular
      emission (47%) dominates at industrial site to PM(10). Paved road, field burning
      and wood combustion contributed 21%, 7% and 1% at residential site, while coal
      combustion, metal industry and soil dust contributed 34%, 1% and 1% at industrial
      site, respectively, to PM(10) during the study period. The contributors to TSP
      included coal combustion (37%), soil dust (19%), road dust (17%) and diesel
      combustion (15%) at residential site, while soil dust (36%), coal combustion
      (17%), solid waste (17%), road dust (16%) and tyre wear (7%) at industrial site.
      Significant seasonal variations of the particulate matters have been observed
      during the study period. In the monitoring sites total carbon, organic carbon and
      iron were found to be the marker species of road dust, while organic carbon,
      total carbon, chloride and sulfate have been observed as the marker species of
      soil dust in TSP.

PMID- 16987606
TI  - Deficits in involuntary attention switching in obstructive sleep apnea syndrome.
AB  - Cognitive functions are altered in patients with obstructive sleep apnea syndrome
      (OSAS) and it has been proposed that vigilance and attentional deficits play a
      pivotal role in all aspects of these deficits. One way to assess attentional
      system integrity is the study of event-related-potentials (ERP), but only a few
      ERP studies have been conducted in patients with OSAS. The aim of the study was
      to use ERP to further assess attentional impairments in these patients. Thirteen
      OSAS patients and 13 age-matched controls underwent a night of polysomnographic
      recording. Each subject was also tested with an ERP paradigm where standard (95%,
      1000Hz), high deviant (2.5%, 1250Hz) and low deviant (2.5%, 1050Hz) tones were
      presented. Subjects were asked to ignore the stimuli and read during the task.
      Mismatch negativity (MMN) and P3a amplitudes and latencies were measured. No
      between-group difference was observed for sleep stages, except a lower percentage
      of rapid eye movement (REM) sleep in patients with OSAS (p<0.01). Moreover, the
      OSAS group showed a higher micro-arousal index and more sleep transitions than
      the control group (p<0.05). A significant group effect was found for the
      amplitude of the P3a component (p<0.05) that was lower in patients with OSAS for
      both high and low deviant tones. No between-group difference was found for the
      MMN and the P3a latencies. In conclusion, patients with OSAS have specific
      alterations of the P3a component that reflects involuntary attention switching,
      but automatic auditory processing assessed by MMN appears to be preserved.

PMID- 16987607
TI  - Nicotinamide reduces acute cortical neuronal death and edema in the traumatically
      injured brain.
AB  - Previous studies have shown that administration of nicotinamide (Vitamin B(3)) in
      animal models of traumatic brain injury (TBI) and ischemia significantly reduced
      the size of infarction or injury and improved functional recovery. The present
      study evaluated the ability of nicotinamide to provide acute neuroprotection and
      edema reduction following TBI. Groups of rats were assigned to nicotinamide
      (500mg/kg) or saline (1.0ml/kg) treatment conditions and received contusion
      injuries or sham surgeries. Drug treatment was administered 15min following
      injury. Brains were harvested 24h later and either processed for histology or
      water content. Frozen sections were stained with the degenerating neuron stain
      (Fluoro-Jade B) (FJ) and cell counts were performed at the site of injury.
      Additional brains were processed for water content (a measure of injury-induced
      edema). Results of this study showed that administration of nicotinamide
      following TBI significantly reduced the number of FJ(+) neurons in the injured
      cortex compared to saline-treated animals. Examination of the water content of
      the brains also revealed that administration of nicotinamide significantly
      attenuated the amount of water compared to saline-treated animals in the injured
      cortex. These results indicate that nicotinamide administration significantly
      reduced neuronal death and attenuated cerebral edema following injury. The
      current findings suggest that nicotinamide significantly modulates acute
      pathophysiological processes following injury and that this may account for its
      beneficial effects on recovery of function following injury.

PMID- 16987608
TI  - Transition of ovalbumin to thermostable structure entails conformational changes
      involving the reactive center loop.
AB  - Ovalbumin is a serpin without inhibitory activity against proteases. During
      embryonic development, ovalbumin in the native (N) form undergoes changes and
      takes a heat-stable form, which was previously named HS-ovalbumin. It has been
      known that N-ovalbumin is artificially converted to another thermostable form
      called S-ovalbumin by heating at an alkaline pH. Here, we characterized further
      the three ovalbumin forms, N, HS, and S. The epitope of the monoclonal antibody
      2B3/2H11, which recognizes N- and HS-ovalbumin but not S-ovalbumin, was found to
      reside in the region Glu-Val-Val-Gly-Ala-Ser-Glu-Ala-Gly-Val-Asp-Ala-Ala-Ser-Val
      Ser-Glu-Glu-Phe-Arg, which corresponds to 340-359 of amino acid residues and is
      contained in the reactive center loop (RCL). Removal of RCL by elastase or
      subtilisin mitigated binding of the antibody. Dephosphorylation experiments
      indicated that the phosphorylated Ser-344 residue located on RCL is crucial for
      the epitope recognition. We suggest that the shift to the heat-stable form of
      ovalbumin accompanies a movement of RCL.

PMID- 16987609
TI  - Environmental enrichment decreases responding for visual novelty.
AB  - Previous research has demonstrated that rats reared in an enriched condition (EC)
      with novel objects and social partners self-administer less amphetamine compared
      to rats raised in an isolated condition (IC). However, it is unclear if the
      enrichment-induced decrease in stimulant self-administration generalizes to non
      drug rewards such as those provided by novel environmental stimuli. In the
      current study, EC, IC, and social condition (SC) rats were raised from 21 to 51
      days of age before being tested in a two-lever operant conditioning chamber in
      which responding on one lever (active lever) resulted in illumination of a cue
      light. In Experiment 1, rats were initially assessed for baseline responding (no
      contingency) and then the contingent light was introduced. EC rats responded less
      than IC rats for the contingent light stimulus; however, EC rats also displayed a
      lower rate of baseline responding. In Experiment 2, rats were trained initially
      to lever press for a sucrose reward to decrease differences in baseline
      responding. While sucrose pretraining decreased baseline response differences
      between groups, EC rats still responded less for the contingent light stimulus
      than IC or SC rats. These results suggest that environmental enrichment decreases
      the incentive value of visual novelty.

PMID- 16987610
TI  - Religion and alcohol in the U.S. National Alcohol Survey: how important is
      religion for abstention and drinking?
AB  - OBJECTIVE: This paper examines the relative importance of three religion
      variables (religious preference, religiosity, and alcohol proscription) and eight
      demographic variables (gender, ethnicity, education, income, marital status, age,
      region, and employment status) as statistical predictors of drinking versus
      abstention and moderate versus heavy drinking. METHOD: Data from 7370 telephone
      interviews from the 2000 National Alcohol Survey are analyzed using bivariate
      cross-tabulations and multiple logistic regression. RESULTS: When analyzed by
      religious preference groups, the NAS showed diverse patterns of abstention and
      drinking that suggest that religion variables are important for drinking
      behaviors. It was found that the religion variables are strongly associated with
      abstention. For statistical prediction of heavy versus moderate drinking,
      religion variables significantly improve model fit but are secondary to gender
      and age. CONCLUSIONS: Religion variables are important for drinking patterns,
      especially abstention. The relationship of religion to lower levels of alcohol
      abuse merits further study, such as investigating religious denominations with
      healthy patterns of abstention and moderate drinking, to learn how these norms
      are initiated and maintained. Such knowledge has promise of application in
      programs for prevention and treatment of alcohol problems.

PMID- 16987611
TI  - Evidence for specificity of transmission of alcohol and nicotine dependence in an
      offspring of twins design.
AB  - Alcohol dependence (AD) and nicotine dependence (ND) have been shown to co-occur.
      Results from twin studies implicate the role of genetics in the etiology of both
      ND and AD with substantial, yet incomplete, overlap. To test for specificity of
      transmission of AD and ND in an offspring of twins sample we analyzed data from a
      study of adolescent and adult offspring of twin fathers ascertained from the
      Vietnam Era Twin Registry. This sample consists of 1213 twin fathers, 862
      biologic or rearing mothers, and 1270 offspring. Offspring were allocated to one
      of four risk groups for AD based on twin fathers' zygosity and father's and
      cotwins AD history. Offspring DSM-IV AD and ND were measured by structured
      diagnostic interview. Paternal AD and ND were significantly associated with
      offspring AD and ND, respectively. Bivariate probit regression results suggest
      specificity for transmission of AD and ND. This remained constant after
      controlling for offspring demographics and psychopathology and maternal AD and
      ND. Despite the substantial genetic overlap between the two disorders, there is
      evidence for genetic effects specific for AD and ND.

PMID- 16987613
TI  - Stochastic epigenetic silencing of retrotransposons: does stability come with
      age?
AB  - It has been hypothesized that phenotypic variation in mammals could in part be
      due to incomplete and variable silencing of retrotransposons in somatic cells.
      This theory is based on the fact that some recent endogenous retroviral (ERV)
      insertions in the mouse exert variable effects on genes in isogenic animals,
      depending on the variable state of ERV methylation. In this article, we review
      the evidence for this and related phenomena and suggest that such stochastic
      epigenetic silencing is restricted to very recent insertions. We also present a
      model to explain the acquisition of a more stable epigenetic state for
      transposable element insertions through time.

PMID- 16987612
TI  - Who is becoming hallucinogen dependent soon after hallucinogen use starts?
AB  - This study, based upon epidemiological survey data from the United States (U.S.)
      National Household Surveys on Drug Abuse (NHSDA) from 2000 to 2001, presents new
      estimates for the risk of developing a hallucinogen dependence syndrome within 24
      months after first use of any hallucinogen (median elapsed time approximately 12
      months). Subgroup variations in risk of becoming hallucinogen dependent also are
      explored. Estimates are derived from the NHSDA representative samples of non
      institutionalized U.S. residents ages 12 and older (n=114,241). A total of 2035
      respondents had used hallucinogens for the first time within 24 months prior to
      assessment. An estimated 2-3% of these recent-onset hallucinogen users had become
      dependent on hallucinogens, according to the NHSDA DSM-IV computerized diagnostic
      algorithm. Controlling for sociodemographic and other drug use covariates, very
      early first use of hallucinogens (age 10-11 years) is associated with increased
      risk of hallucinogen dependence (p<0.01). Excess risk of developing hallucinogen
      dependence was found in association with recent-onset use of mescaline; excess
      risk also was found for recent-onset users of ecstasy and of PCP. This study's
      evidence is consistent with prior evidence on a tangible but quite infrequent
      dependence syndrome soon after the start of hallucinogen use; it offers leads
      that can be confirmed or disconfirmed in future investigations.

PMID- 16987614
TI  - Alveolate and chlorophycean mitochondrial cox2 genes split twice independently.
AB  - The mitochondrial gene for COXII is typically encoded in the organelle genome,
      however in some members of two unrelated groups, Apicomplexa and Chlorophyceae,
      cox2 is split into two genes, and both are encoded in the nucleus. Rare genomic
      changes (RGCs) have acquired popularity as phylogenetic markers, and accordingly
      this rearrangement of cox2 has been used to infer a possible source of the
      apicomplexan plastid, the apicoplast, a topic that continues to attract much
      debate. Accurate interpretation of RGCs, however, is critically dependent on
      appropriate sampling of the character state of interest amongst relevant taxa.
      Dinoflagellates form the sister taxon to Apicomplexa, and therefore the state of
      their cox2 is essential to the interpretation of this apparent RGC. Here we
      present the first complete cox2 data from dinoflagellates, that suggests despite
      the remarkable similarity of cox2 seen in Alveolates and Chlorophyceae, this gene
      reorganization arose independently in these two groups, not through lateral
      transfer as previously suggested.

PMID- 16987615
TI  - Are GC-rich isochores vanishing in mammals?
AB  - Several studies of nucleotide substitution patterns in mammalian species
      suggested that GC-rich isochores might be vanishing in mammalian genomes.
      However, the number of genes and the number of genomes included in these studies
      might not have given a reliable broad view of the trend in GC change in mammals.
      It is therefore worth exploiting this issue with a broader coverage of mammalian
      genomes using a reliable approach, the maximum likelihood approach. We have
      applied two maximum likelihood methods to infer the ancestral GC contents of 176
      mammalian genes from representative eutherian species and at least one marsupial
      species. Except for a large GC decrease in marsupial genes, we found no general
      decreasing trend in GC content in GC-rich genes or in other genes among eutherian
      mammals; indeed, the GC content of GC-rich genes appears to have increased in
      recent times in some genomes, e.g., the rabbit. For the large GC decrease in
      marsupials, it could be mainly due to the great reduction in chromosome number,
      which could lead to a large reduction in recombination rate and thus also a large
      reduction in the rate of gene conversion. Since many eutherian mammals still
      maintain a fairly large number of chromosomes, it is unlikely that GC-rich
      isochores are vanishing in these mammals.

PMID- 16987616
TI  - Revisiting the directional mutation pressure theory: the analysis of a particular
      genomic structure in Leishmania major.
AB  - This paper reports the existence of a significant negative correlation between
      GC12 and GC3 in the recently sequenced genome of Leishmania major. This result
      contradicts the previous evidence that the compositional correlations between
      codon positions are universal. Moreover, it challenges the interpretation of the
      GC12 vs. GC3 linear regression slope as the relative neutrality of GC12, within
      the framework of the directional mutation pressure theory [Sueoka, N., 1988.
      Directional mutational pressure and neutral molecular evolution. P Natl Acad Sci
      USA 85, 2653-2657.]. The analysis of the codon usage pattern for L. major shows
      that codon choice is most likely influenced by both mutation pressure and
      translational selection. Dinucleotide frequencies were also analysed; our results
      do not support the existence of an unusual neighbour-dependent mutation bias in
      this genome. We developed two evolutionary models that could explain the origin
      of the negative GC12/GC3 correlation. The first model is based on the effect of
      translational selection on the GC3 the second one is based on a potential
      mutation bias combined with purifying selection at the amino-acid level. Both
      models predict a negative GC12/GC3 correlation at the equilibrium. The potential
      implications of these results for this aspect of the directional mutation
      pressure theory are discussed. We conclude that the particular case of L. major
      should lead to a careful reevaluation of several hypotheses of this theory. The
      origin of the negative GC12/GC3 correlation remains for now an open question.

PMID- 16987617
TI  - An isolate of Prototheca wickerhamii from systemic canine protothecosis.
AB  - The isolate from a canine disseminated protothecosis was identified to be
      Prototheca wickerhamii by its morphological and biochemical characteristics. The
      isolate was grouped into a cluster identical to the type strain of P.
      wickerhamii, ATCC 16529(T) in phylogenetic trees based on the small subunit (SSU)
      and the 5' end of the large subunit (LSU) ribosomal DNA (rDNA); the cluster was
      close to that including the other Prototheca species. However, the strains of P.
      wickerhamii, SAG 263-11 and Pore 1283 belonged to a cluster different from the
      other isolates of Prototheca species and closely related to those of
      Auxenochorella species. Therefore, P. wickerhamii could be divided into two
      distinct genetic groups, one group close to the other Prototheca spp. including a
      standard strain of P. wickerhamii, and another group consisting of isolates
      previously reported to be close to the Auxenochorella species.

PMID- 16987618
TI  - Estimation of Salmonella prevalence on individual-level based upon pooled swab
      samples from swine carcasses.
AB  - Pooling of samples might be an effective means to increase cost-effectiveness in
      routine surveillance. The present study assessed the effect on the sensitivity of
      detection of Salmonella when pooling swab samples from swine carcasses compared
      to individual analyses. A total of 18,984 samples from nine Danish swine
      abattoirs were collected during 1 year, covering 2017 slaughter days. At each
      abattoir, swab samples were taken on a daily basis from 10 carcasses randomly
      selected. From each carcass, an area of 3 cm x 100 cm was swabbed. Five of these
      samples were analysed individually and the other five were analysed as one pooled
      sample. Standard culture methods were used. A logistic regression model was
      built, where the response was whether a sample was Salmonella positive or not.
      The explanatory factors were abattoir, type of sampling (individual or pooled
      sample), and season of year 2000 (four quarters). The odds ratio (OR) of the
      effect of type of sampling in the logistic model accounting for abattoir and
      season was interpreted as the conversion factor between pooled and individual
      sample prevalence. The results of the individually analysed samples showed a low
      prevalence of Salmonella (1.4%). When Salmonella was isolated, mostly only one
      positive sample was found among the five individually analysed samples per
      slaughter day. On a few days >1 positive samples' were found (9 out of 2017 days
      approximately 0.4%). The pooled sample prevalence was 4.1%. Because the
      individual prevalence was low, the pooled sample prevalence would have been
      around five times higher than the individual-level prevalence-if there had been
      no loss of sensitivity. However, we found that due to loss of sensitivity the
      pooled prevalence was only three times higher (OR = 2.7; CI 2.0-3.7). Therefore,
      a conversion factor of 3 instead of 5 should be applied to calculate the
      individual prevalence from a pooled prevalence. This approach has been used in
      the national surveillance of Danish pork since 2001. The estimated conversion
      factor and accept of pooling samples do not necessarily apply to a population
      with a higher prevalence or to other types of samples (e.g. faeces or lymph
      nodes) or diagnostic procedures.

PMID- 16987619
TI  - Mutant prevention concentration of ciprofloxacin and enrofloxacin against
      Escherichia coli, Salmonella Typhimurium and Pseudomonas aeruginosa.
AB  - The mutant prevention concentration (MPC) is a new concept meant to face the
      increased prevalence of antibiotic resistance by using antibiotic concentrations
      able to prevent the selection of single-step resistant mutants. In the present
      study, the MPCs of ciprofloxacin and enrofloxacin were evaluated against fully
      susceptible strains of Escherichia coli, Salmonella Typhimurium and Pseudomonas
      aeruginosa. Additionally, representative single-step mutants arising after
      exposure to sub-MPC antibiotic concentrations were investigated for molecular
      basis of their fluoroquinolone resistance phenotypes. MPC value was recorded when
      more than 10(10) CFU/mL were spread on Mueller Hinton Agar supplemented with
      different antibiotic concentrations (from 1X to 16X MIC value). MICs of original
      strains as well as single-step mutants were determined in presence or absence of
      the Efflux Pump Inhibitor Phe-Arg-beta-naphthylamide (PAbetaN). Moreover point
      mutations in the QRDR of the gyrA and parC genes were investigated by sequencing.
      The enrofloxacin MPC values were 4-16-fold higher than ciprofloxacin values. E.
      coli and S. Typhimurium representative single-step mutants showed reduced
      susceptibilities associated with point mutations in the QRDR of the gyrA gene or
      efflux pump system. P. aeruginosa mutants showed resistance phenotypes associated
      predominantly with efflux pump system activity. According to in vitro MPC data,
      ciprofloxacin showed a better efficacy than enrofloxacin, in preventing the
      selection of E. coli, S. Typhimurium and P. aeruginosa single-step mutants.
      However, in relation to AUC/MPC ratio, the MPC concept can be applied in vivo to
      ciprofloxacin and enrofloxacin for E. coli and S. Typhimurium but not for P.
      aeruginosa.

PMID- 16987620
TI  - Defining critical periods for itraconazole-induced cleft palate, limb defects and
      axial skeletal malformations in the mouse.
AB  - The main aim of the study was to identify the critical periods of susceptibility
      for itraconazole-mediated teratogenesis in the mouse. Pregnant ICR (CD-1) mice
      received a single oral administration of itraconazole at 50 mg/kg b.w., 150 mg/kg
      b.w. or 250 mg/kg b.w. on gestation day 8, 9, 10, 11 or 12. Control animals were
      administered with vehicle on gestation days 8-12. The gestational outcome was
      evaluated near term, on gestation day 18. Treatment-related morphological
      findings, as they can be evaluated by external, visceral and skeletal
      examination, mainly included cleft palate, limb defects and axial skeletal
      malformations. Cleft palate and limb defects resulted after single exposures
      between gestation days 9 and 11, with a tendency toward maximal response on
      gestation day 10. Significant incidences of axial skeletal defects were seen
      exclusively on gestation days 8 and 9. Exposure on gestation day 12 did not yield
      significant teratogenic responses. Cleft palate was the most sensitive
      teratogenic response, being the only developmental lesion associated to exposure
      to itraconazole at 150 mg/kg b.w.

PMID- 16987621
TI  - In vitro storage of unfertilized ova of endangered Caspian brown trout (Salmo
      trutta caspius) in artificial media.
AB  - In order to study the effects of storage media and time of storage on the
      viability of unfertilized eggs of endangered Caspian brown trout (Salmo trutta
      caspius), the ova of this fish was stored in coelomic fluid and Cortland
      artificial media at 2-3 degrees C for 120 h. In this research, Cortland
      artificial medium was buffered with 20 mM of three different buffers: Hepes
      (C(8)H(18)N(2)O(4)S), Tris-HCl (C(4)H(11)NO(3)-HCl) and sodium salt Hepes
      (C(8)H(17)N(2)O(4)SNa). The pH of these media were adjusted according to natural
      pH of coelomic fluid. The eggs that stored in these media fertilized at times 0 h
      (eggs fertilized prior to storage), 48, 72 and 120 h of post-stripping, using
      fresh and pooled sperm obtained from four to six males. According to the results
      of present study, time of storage showed a significant (p<0.05) main effect on
      eyeing, hatching and eyed eggs mortality rates. Eyeing and hatching rates
      significantly (p<0.05) decreased from 97.4+/-2.1% and 95.1+/-4.4% at time 0 (eggs
      fertilized prior to storage) to 77.9+/-3% and 65.5+/-5% after 120 h of storage.
      Within a similar period of time, eyed eggs mortality significantly (p<0.05)
      increased from 2.4+/-2.4% to 17.2+/-3.9%. No significant (p>0.05) main effect was
      found among media buffered with Tris-HCl (82.8+/-3.2%, 73.4+/-5.4%, 12.1+/-4.5%),
      Hepes (88.2+/-3.4%, 80.7+/-5.5%, 9.3+/-3.4%), sodium salt Hepes (77.8+/-3.8%,
      69.3+/-5.7%, 12.2+/-3.9%) and coelomic fluid (84.8+/-3.8%, 77.7+/-5.1%, 8.9+/
      2.7%) for eyeing, hatching and eyed eggs mortality rates. There was a negative
      correlation (r=-0.895, p<0.001) between eyed eggs mortality and hatching rates.
      In conclusion, unfertilized eggs of endangered Caspian brown trout can be
      successfully stored for 48 h without significant loss of fertility. But, storage
      for 120 h results in the falling of hatching rate. In addition, no significant
      difference was found between viability rates of ova stored in coelomic fluid and
      artificial media, 120 h post-storage. It reveals that artificial media could be
      substituted for coelomic fluid as storage medium at least for 120 h in Caspian
      brown trout.

PMID- 16987622
TI  - Studies of male reproduction in captive African wild dogs (Lycaon pictus).
AB  - Implementation of assisted breeding in the captive African wild dog is restricted
      by a current lack of knowledge on their reproductive physiology and the apparent
      difficulty of effectively manipulating the complex social dynamic of the pack in
      order to conduct reproductive procedures. In this study, we describe protocols
      for the safe and repeated capture and restraint of the African wild dog (n=7) as
      well as techniques for assessment of male reproductive function, semen collection
      and preservation. In a serendipitous finding, captive African wild dogs appeared
      to display significant seasonal change in male reproduction. Testicular volume
      and tone, spermatorrhea and the ability to collect semen by electroejaculation
      all increased significantly during late summer and then subsequently declined by
      early spring. While there were no detectable seasonal changes in testosterone
      concentration in the population as whole, the alpha-dominant male in both years
      of the study, had a highly elevated testosterone concentration compared to
      subordinate males. Semen collection by electroejaculation during the late summer
      was most effective in peri-pubertal males (15 months) when all seven
      electroejaculates were of adequate quality for cryopreservation. In the second
      breeding season (27 months), there were numerous changes in the pack hierarchy
      and electroejaculation was not as successful (3/7). The characteristics of
      electroejaculated semen collected in the breeding season are described for seven
      animals including the first descriptions and incidence of sperm abnormalities in
      the species. Semen (n=7) was frozen using a Tris-citrate fructose buffer and
      final egg yolk and glycerol concentration of 20% and 4%, respectively. Sperm were
      loaded into 0.25 mL straws, frozen in liquid nitrogen vapor and then thawed at 37
      degrees C. Initial post-thaw survival of spermatozoa was encouraging (% motile:
      31.8+/-5.8%; rate: 2.8+/-0.3; % intact plasma membranes: 33.4+/-5.3% and the % of
      damaged acrosomes: 4.4+/-1.5%) but following 2 h incubation at 37 degrees C, post
      thaw survival declined markedly.

PMID- 16987623
TI  - Influence of composition and preparation parameters on the properties of aqueous
      monoolein dispersions.
AB  - Colloidal cubic phase particles formed in the monoolein/poloxamer/water system
      are being investigated as potential drug carriers for, e.g., intravenous
      administration. Preparation methods must, however, still be further developed to
      reliably yield monoolein dispersions with cubic particles in a size range
      acceptable for i.v. administration and adequate long-term stability. In this
      context, the influence of different composition and preparation parameters on the
      properties of monoolein dispersions prepared by high-pressure homogenization was
      studied. High pressure homogenization of coarse poloxamer 407-stabilized
      monoolein/water mixtures leads to dispersions with a large fraction of micrometer
      sized particles at low poloxamer concentrations. Higher poloxamer concentrations
      lead to lower mean particle sizes but the fraction of cubic particles becomes
      smaller and vesicular particles are observed instead. A study of the
      characteristics of a dispersion with a standard composition indicated that the
      homogenization temperature has a much stronger influence on the dispersion
      properties than the homogenization pressure or the type of homogenizer used.
      Temperatures around 40-60 degrees C lead to the most favorable dispersion
      properties. The high temperature sensitivity of the preparation process appears
      to be at least partly correlated with the phase behavior of the dispersed
      particles determined by temperature-dependent X-ray diffraction.

PMID- 16987624
TI  - Controlled release of huperzine A from biodegradable microspheres: In vitro and
      in vivo studies.
AB  - The objective of the present work was to further study the in vitro
      characteristics, in vivo pharmacokinetics and pharmacodynamics of huperzine A
      (HupA) loaded biodegradable microspheres designed for sustained release of HupA
      over several weeks. A conventional o/w emulsion-solvent evaporation method was
      used to incorporate HupA, which is of interest in the palliative treatment of
      Alzheimer's disease (AD), into end-group uncapped poly(D,L-lactide-co-glycolide)
      (PLG-H). A prolonged in vitro drug release profile was observed, with a complete
      release of the incorporated drug within 5-6 weeks. The in vivo pharmacokinetics
      study of HupA loaded microspheres showed sustained plasma HupA concentration-time
      profile after subcutaneous injection into rats. The pharmacodynamics evaluated by
      determination of the activity of acetylcholinesterase in the rat cortex also
      showed a prolonged pharmacological response. Both the in vitro release and in
      vivo pharmacological responses correlated well with the in vivo pharmacokinetics
      profile. The results suggest the potential use of HupA-loaded biodegradable
      microspheres for treatment of AD over long periods.

PMID- 16987625
TI  - Lipid lowering effect of S-methyl cysteine sulfoxide from Allium cepa Linn in
      high cholesterol diet fed rats.
AB  - The lipid lowering action of S-methyl cysteine sulfoxide (SMCS) isolated from
      Allium cepa Linn (family: Liliaceae) was investigated in Sprague-Dawley rats fed
      on 1% cholesterol diet, in comparison to the hypolipidemic drug gugulipid.
      Administration of SMCS at a dose of 200mg/kg body weight for 45 days ameliorated
      the hyperlipidemic condition. The lipid profile in serum and tissues showed that
      concentrations of cholesterol, triglyceride and phospholipids were significantly
      reduced when compared to their untreated counterparts. The total lipoprotein
      lipase activity in the adipose tissue was decreased with also a decrease in the
      free fatty acid levels in serum and tissues. The activities of the lipogenic
      enzymes glucose 6-phosphate dehydrogenase and malic enzyme as also of HMG CoA
      reductase in the tissues remained low on treatment indicating that both the drugs
      did not favor lipogenesis and cholesterogenesis in the hyperlipidemic animals.
      The fecal excretion of bile acids and sterols was further increased upon
      treatment with the drugs. The results are directive to that both gugulipid and
      SMCS cause reduction of endogenous lipogenesis, increase catabolism of lipids and
      subsequent excretion of metabolic by-products through the intestinal tract.
      However, gugulipid is a better drug than SMCS at a low dose of 50mg/kg body
      weight.

PMID- 16987626
TI  - Plants species in the folk medicine of Montecorvino Rovella (inland Campania,
      Italy).
AB  - An ethnobotanical survey was conducted in the territory of Montecorvino Rovella
      (MR), inland Campania, Italy. Information on traditional uses of 95 botanical
      taxa was collected; more than half of which are used to treat a wide range of
      diseases, ranging from pains of different origins, to skin problems, and diseases
      of the respiratory system. For each medicinal species, data were collected
      including the vernacular names, preparation, plant part, and therapeutic use.
      Twenty-four out of the 57 medicinal plants listed have a therapeutic use not
      previously reported in Campania and neighbouring regions. Plant uses by
      Montecorvino inhabitants are compared with those described in medical and
      botanical literature by Campanian authors from the last three centuries.

PMID- 16987627
TI  - Therapeutic effect of Chinese medicine formula DSQRL on experimental pulmonary
      fibrosis.
AB  - Pulmonary fibrosis (PF) is a restrictive lung disease that may occur
      idiopathically or as a complication of many diseases. The outcome of the current
      treatment by glucocorticoids remains very unsatisfactory. This study has tested a
      new Chinese medicine formula DSQRL for the treatment of experimental PF in
      comparison with prednisone. Seventy-two rats with PF induced by CCl(4) were
      randomly divided into four groups to undertake the treatment of either (a) high
      dose of prednisone; (b) Chinese medicine formula DSQRL; (c) combined treatment of
      the above two; or (d) tap water of the same volume. At the end of 30 days
      treatment, the DSQRL treatment achieved a better outcome (p<0.05) than prednisone
      in terms of histological examination, bronchoalveolar lavage fluid analysis,
      hydroxyproline assay and complications. The observations support further
      investigation and clinical trials of this Chinese medicinal formula for the
      treatment of PF.

PMID- 16987628
TI  - Accuracy of 16-detector multislice spiral computed tomography in the initial
      evaluation of dilated cardiomyopathy.
AB  - BACKGROUND: Multislice Computed Tomography (MSCT) recently proved its accuracy in
      the detection of coronary artery disease (CAD). It can also give information
      about left ventricular function and venous network anatomy. We here sought to
      validate a MSCT-based strategy in the initial evaluation of patients with dilated
      cardiomyopathy (DCM). METHODS: 36 patients with DCM underwent cardiac MSCT before
      conventional coronary angiography with ventriculography. We analysed arterial
      calcium score (Agatston score equivalent: ASE), coronary stenosis, left
      ventricular parameters and venous network. RESULTS: The sensitivity of a MSCT
      based strategy in detecting significant CAD was 100% and the specificity 80%. The
      positive and negative predictive values were respectively 67% and 100%. For ASE
      <1.000 (75% of patients), MSCT detected all non-CAD patients without one (motion
      artifacts), enabling conventional angiography to be avoided in 21/27 patients
      (77.7%). For ASE > or =1000, MSCT enabled conventional angiography to be avoided
      in only 2/9 patients (22.2%). The ventricle was assessable in 83.4% (30 patients)
      on MSCT. Correlation coefficient Rs with ventriculography were 0.78 (p<0.0001),
      0.77 (p<0.0001) and 0.82 (p<0.0001) respectively for end-diastolic volume, end
      systolic volume and EF. The venous network was assessable in all patients both on
      MSCT and angiography. CONCLUSION: In patients undergoing an initial evaluation of
      DCM, MSCT appears to be an effective alternative to conventional angiography. The
      following attitude may be proposed: when ASE >1.000, conventional coronary
      angiography is mandatory due to MSCT's poor interest in such cases; when ASE
      <1.000, a contrast-enhanced MSCT may, when normal, replace coronary angiography.

PMID- 16987629
TI  - Tubular carcinoma of the breast: mammographic, sonographic, clinical and
      pathologic findings.
AB  - PURPOSE: To determine and quantitate the radiological characteristics of tubular
      carcinoma of the breast, to report clinical and pathologic findings and to define
      findings at follow-up. MATERIALS AND METHODS: A retrospective review of records
      of 2872 women who received a diagnosis of breast carcinoma between January 1988
      and January 2006 revealed 32 histopathologically proven pure tubular carcinoma of
      the breast. Analysis included history; findings at physical examination,
      mammography, and sonography (US) at the time of diagnosis and in postoperative
      follow-up and histopathological results. RESULTS: Fifty-nine percent of the
      patients (n=19) presented with a palpable mass. The mammographic findings were a
      mass in 23 (72%), a mass with microcalcifications in 2 (6%), asymmetric focal
      density in 1 (3%), architectural distortion in 1 (3%) and negative in 5 (16%) of
      the 32 patients. Most (96%) masses had spiculated margins. US depicted 30 masses
      in 29 patients, all of which were hypoechoic, mostly (n=27, 90%) with posterior
      acoustic shadowing. The cancer was clinically occult in 41% (n=13),
      mammographically occult in 16% (n=5), and sonographically occult in 6% (n=2) of
      the patients. Histologically, the tumor was multifocal in 3% (n=1) of the
      patients. Four (13%) patients developed contralateral breast carcinoma at follow
      up. CONCLUSION: Tubular carcinoma has a variety of presentations, but it is
      mostly seen on mammography as a small spiculated mass, and on sonography as an
      irregular mass with posterior acoustic shadowing. Although tubular carcinoma is
      known as a well-differentiated tumor with excellent prognosis, the mammographic
      follow-up of the contralateral breast is important.

PMID- 16987630
TI  - Legionnaire's pneumonia: is there really an interstitial disease?
AB  - OBJECTIVE: Legionella pneumonia is usually classified as "atypical pneumonia",
      which suggests a predominance of interstitial patterns in chest X-rays. Based on
      a selection of recent clinical cases and a brief review of the literature, the
      aim of the study is to clarify, how far the actual radiological findings would be
      consistent with these expectations. PATIENTS AND METHODS: A retrospective
      analysis of 18 epidemic personal cases and a review of the literature data were
      performed to describe the chest X-ray findings of Legionella pneumophila (LP)
      community acquired pneumonia. X-ray review was performed simultaneously and in
      consensus by two radiologists (J.P.T., E.C.) and a physician (C.G.). RESULTS:
      From our series, 17 patients had an abnormal chest X-ray on admission. Among
      these pathological X-ray cases, infiltrates were more often confluent (n=16), or
      patchy (n=7), rather than interstitial (n=1). Fifteen patients had infiltrates
      involving the lower lung fields. Bilateral distribution of abnormalities and
      pleural effusion were each observed in three cases. Radiological findings
      deteriorated between the second and seventh days following admission,
      particularly in the form of patchy infiltrates with pleural effusion. The review
      of the literature is consistent with these findings, by reporting prevalent
      confluent or patchy infiltrates. CONCLUSIONS: These findings are consistent with
      the physiopathological particularity of this affection and incite us to avoid the
      classification "atypical pneumonia" in radiologic terminology. This term is more
      appropriate for clinical and microbiological use.

PMID- 16987631
TI  - Evaluation of three-dimensional navigator-gated whole heart MR coronary
      angiography: the importance of systolic imaging in subjects with high heart
      rates.
AB  - PURPOSE: To evaluate the influence of heart rate (HR) on magnetic resonance
      coronary angiography (MRCA) image quality in diastolic and systolic phases.
      MATERIALS AND METHODS: Twenty-seven healthy volunteers (9 men; 33+/-9 years, HR
      53-110 bpm), were evaluated with the electrocardiography and three-dimensional
      navigator-gating MRCA in a 1.5-T MR scanner (Avanto, Siemens) in diastolic and
      systolic phases (steady-state free precession; TR/TE/flip angle=3.2 ms/1.6 ms/90
      degrees). The timing of scanning was individually adapted to the cardiac rest
      periods obtained in the prescanning, by visually identifying when the movement of
      right coronary artery was minimized during diastole and systole. Images of two
      phases were side-by-side compared on a four-point scale (from 1=poor to
      4=excellent visibility; score of 3 or 4 as diagnostic). RESULTS: Of 13 subjects
      with HR < or =65 bpm (low HR group, mean 59.8+/-4.9 bpm, range 53-65), the image
      quality scores were significantly better than that with higher heart rates
      (73.9+/-9.0 bpm, range 68-110) in diastolic MRCA. The image quality was
      significantly improved during systole in high HR group. Overall, 91.3% of low HR
      group had MRCA image of diagnostic quality acquired at diastole, while 88.3% of
      high HR group had diagnostic images at systole by segmental analysis (p=NS).
      CONCLUSIONS: MRCA at systole offered superior quality in patients with high heart
      rates.

PMID- 16987632
TI  - Exploring the discourse between genetic counselors and Orthodox Jewish community
      members related to reproductive genetic technology.
AB  - OBJECTIVE: Genetic technology is complex, relatively new and involves sensitive
      issues pertaining to personhood and reproduction. While ethno cultural barriers
      to genetic care are well documented, little attention has been devoted to
      understanding religious beliefs pertaining to genetic services. This study
      evaluated the discourse between genetic counselors and Orthodox Jewish community
      members' perceptions of reproductive genetic technology. METHODS: A cross section
      of the Orthodox Jewish community was sampled through purposeful and snowball
      recruitment for in-depth interviews with key informants. RESULTS: Genetic
      counselors felt apprehensive about serving the Orthodox Jewish population and
      were unaware of social norms, religious and cultural practices unique to this
      population. Similarly, Orthodox Jewish consumers exhibited major misgivings about
      genetic testing. Importantly, stereotypic expectations by both counselors and
      consumers exacerbated existing communication difficulties. CONCLUSION: Cultural
      differences and poor communication between genetic counselors and Orthodox Jewish
      community members impeded the ability of the Orthodox Jewish community to utilize
      genetic services. PRACTICE IMPLICATIONS: This work illuminates complex issues
      pertaining to medical encounters between providers and patients with ideological,
      social and cultural differences. In particular, issues of access to care and
      transcultural competence in serving religious minority groups, such as Orthodox
      Jews are presented. On the whole, this group is largely unrecognized in the
      minority health literature in spite of barriers and challenges that they face.
      Findings of this study may have application to other cloistered and highly
      observant religious groups when dealing with reproductive technology and other
      populations with diverse values, beliefs and behaviors pertaining to reproductive
      health.

PMID- 16987633
TI  - Leptin infusion during the early luteal phase in ewes does not affect
      progesterone production.
AB  - Infusion of leptin during the ovine follicular phase has been shown to increase
      progesterone secretion during the subsequent luteal phase. In this study, we have
      assessed the effects of infusing leptin during the early luteal phase. Infusion
      of leptin (2.5 microg/h) into the ovarian artery of ewes with ovarian
      autotransplants (n=5) on day 3 of the luteal phase for 12h did not affect
      progesterone estradiol or LH concentrations compared to control ewes (n=5). These
      results suggest no direct effect of leptin on ovarian function at this stage of
      the estrous cycle.

PMID- 16987634
TI  - Test performance and classification statistics for the Rey Auditory Verbal
      Learning Test in selected clinical samples.
AB  - The Rey Auditory Verbal Learning Test [RAVLT; Rey, A. (1941). L'examen
      psychologique dans les cas d'encephalopathie traumatique. Archives de
      Psychologie, 28, 21] is a commonly used neuropsychological measure that assesses
      verbal learning and memory. Normative data have been compiled [Schmidt, M.
      (1996). Rey Auditory and Verbal Learning Test: A handbook. Los Angeles, CA:
      Western Psychological Services]. When assessing an individual suspected of
      neurological dysfunction, useful comparisons include the extent that the patient
      deviates from healthy peers and also how closely the subject's performance
      matches those with known brain injury. This study provides the means and S.D.'s
      of 392 individuals with documented neurological dysfunction [closed head TBI
      (n=68), neoplasms (n=57), stroke (n=47), Dementia of the Alzheimer's type
      (n=158), and presurgical epilepsy left seizure focus (n=28), presurgical epilepsy
      right seizure focus (n=34)] and 122 patients with no known neurological
      dysfunction and psychiatric complaints. Patients were stratified into three age
      groups, 16-35, 36-59, and 60-88. Data were provided for trials I-V, List B,
      immediate recall, 30-min delayed recall, and recognition. Classification
      characteristics of the RAVLT using [Schmidt, M. (1996). Rey Auditory and Verbal
      Learning Test: A handbook. Los Angeles, CA: Western Psychological Services] meta
      norms found the RAVLT to best distinguish patients suspected of Alzheimer's
      disease from the psychiatric comparison group.

PMID- 16987635
TI  - Proliferative activity in the frog brain: a PCNA-immunohistochemistry analysis.
AB  - By means proliferating cell nuclear antigen (PCNA) immunohistochemistry, we have
      provided a detailed neuroanatomical mapping of proliferative activity during
      development and adulthood in the frog (Rana esculenta) brain. Western blot
      analysis confirmed the presence of this protein in brain extracts from adults and
      tadpoles. Proliferative activity was observed in the ventricular and
      subventricular zones throughout the brain. The present study provides details as
      to which of the morphologically distinguishable brain region(s) has a long
      lasting proliferative activity and in which region this activity undergoes a
      progressive decrease during development. In the subventricular zones of the third
      ventricle, PCNA-labeled cells were particularly abundant in the magnocellular
      preoptic nucleus and the ventromedial thalamic nucleus. It was observed that
      proliferation zones are present practically in all major subdivisions of the
      forebrain, midbrain and hindbrain, including the cerebellum in which PCNA-labeled
      cells were located in the outer granular layer and the inner molecular layer. The
      habenulae, epiphysis and isthmic nuclei never showed the presence of PCNA
      immunoreactive nuclei. The widespread proliferative activity implies that the
      frog brain has a great potential for neurogenesis/gliogenesis not only during
      larval development but also in the adulthood.

PMID- 16987636
TI  - Rapid decision threshold modulation by reward rate in a neural network.
AB  - Optimal performance in two-alternative, free response decision-making tasks can
      be achieved by the drift-diffusion model of decision making--which can be
      implemented in a neural network--as long as the threshold parameter of that model
      can be adapted to different task conditions. Evidence exists that people seek to
      maximize reward in such tasks by modulating response thresholds. However, few
      models have been proposed for threshold adaptation, and none have been
      implemented using neurally plausible mechanisms. Here we propose a neural network
      that adapts thresholds in order to maximize reward rate. The model makes
      predictions regarding optimal performance and provides a benchmark against which
      actual performance can be compared, as well as testable predictions about the way
      in which reward rate may be encoded by neural mechanisms.

PMID- 16987637
TI  - Heterarchical reinforcement-learning model for integration of multiple cortico
      striatal loops: fMRI examination in stimulus-action-reward association learning.
AB  - The brain's most difficult computation in decision-making learning is searching
      for essential information related to rewards among vast multimodal inputs and
      then integrating it into beneficial behaviors. Contextual cues consisting of
      limbic, cognitive, visual, auditory, somatosensory, and motor signals need to be
      associated with both rewards and actions by utilizing an internal representation
      such as reward prediction and reward prediction error. Previous studies have
      suggested that a suitable brain structure for such integration is the neural
      circuitry associated with multiple cortico-striatal loops. However, computational
      exploration still remains into how the information in and around these multiple
      closed loops can be shared and transferred. Here, we propose a "heterarchical
      reinforcement learning" model, where reward prediction made by more limbic and
      cognitive loops is propagated to motor loops by spiral projections between the
      striatum and substantia nigra, assisted by cortical projections to the
      pedunculopontine tegmental nucleus, which sends excitatory input to the
      substantia nigra. The model makes several fMRI-testable predictions of brain
      activity during stimulus-action-reward association learning. The caudate nucleus
      and the cognitive cortical areas are correlated with reward prediction error,
      while the putamen and motor-related areas are correlated with stimulus-action
      dependent reward prediction. Furthermore, a heterogeneous activity pattern within
      the striatum is predicted depending on learning difficulty, i.e., the anterior
      medial caudate nucleus will be correlated more with reward prediction error when
      learning becomes difficult, while the posterior putamen will be correlated more
      with stimulus-action-dependent reward prediction in easy learning. Our fMRI
      results revealed that different cortico-striatal loops are operating, as
      suggested by the proposed model.

PMID- 16987638
TI  - Photoparoxysmal responses in children with chromosomal aberrations.
AB  - Electroencephalographic (EEG) anomalies and epilepsy are commonly observed in the
      clinical picture of patients with chromosomal aberrations. However, no
      investigations have been performed on the relationship between chromosomal
      disorders and photoparoxysmal response (PPR). In this study, we evaluate the
      characteristics of PPRs elicited with intermittent photic stimulation during a
      routine electroencephalogram in children affected by chromosomal anomalies and
      correlated this with the clinical profile of the child. A review of the
      literature has also been performed. PPRs occurred in 14% (4/28) of patients. PPRs
      were brief (<less 5s), self-limited, elicited by several series of flashes, with
      an onset latency between 2 and 9s, and scarcely controlled by anticonvulsants.
      Although further studies are needed to confirm the present data, our observations
      and the review of the literature suggest that patients carrying chromosomal
      anomalies might have a higher risk for photosensitivity when compared to the
      normal population. In these patients, PPR might occur early in life, persist into
      adulthood, and is commonly inscribed in more polymorphic electroclinical
      patterns.

PMID- 16987639
TI  - In vitro activity of cefepime combined with sulbactam against clinical isolates
      of carbapenem-resistant Acinetobacter spp.
AB  - The aim of this study was to assess the in vitro activity of cefepime combined
      with sulbactam against carbapenem-resistant clinical isolates of Acinetobacter
      spp. The checkerboard method was used to determine whether combinations act
      synergistically against these strains. Twenty-three Acinetobacter baumannii and
      one Acinetobacter junii found to be carbapenem resistant were included in the
      study. The susceptibility results for cefepime and sulbactam were interpreted
      according to the guidelines of the Clinical and Laboratory Standards Institute.
      Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922 were used as
      quality control strains. The combination of cefepime and sulbactam demonstrated
      the following interactions: 33.3% (8/24) synergism; 58.3% (14/24) partial
      synergism; 4.2% (1/24) additive; 4.2% (1/24) indifference; and no antagonism
      (minimum and maximum fractional inhibitory concentration index 0.25 and 1.5,
      respectively). According to our in vitro study results, combinations of cefepime
      with sulbactam have moderate synergistic activity against some carbapenem
      resistant strains of Acinetobacter spp., which could be beneficial for the
      treatment of infections due to multidrug-resistant strains of Acinetobacter spp.

PMID- 16987640
TI  - Isolation and partial characterization of a biosurfactant produced by
      Streptococcus thermophilus A.
AB  - Isolation and characterization of the surface active components from the crude
      biosurfactant produced by Streptococcus thermophilus A was studied. A fraction
      rich in glycolipids was obtained by the fractionation of crude biosurfactant
      using hydrophobic interaction chromatography. Molecular (by Fourier transform
      infrared spectroscopy) and elemental compositions (by X-ray photoelectron
      spectroscopy) were determined. Critical micelle concentration achieved was 20
      g/l, allowing for a surface tension value of 36 mJ/m(2). Moreover, this
      glycolipid rich fraction was found to be an anti-adhesive and antimicrobial agent
      against several bacterial and yeast strains isolated from explanted voice
      prostheses. Further purification steps should be carefully analyzed as each
      purification step will increase the costs and decreases the amounts of
      biosurfactants recovered.

PMID- 16987641
TI  - [Prevention of childhood tuberculosis: a powerful strategy for contact
      investigation must accompany any change in BCG vaccination].

PMID- 16987642
TI  - Novel ultra-rapid freezing particle engineering process for enhancement of
      dissolution rates of poorly water-soluble drugs.
AB  - An ultra-rapid freezing (URF) technology has been developed to produce high
      surface area powders composed of solid solutions of an active pharmaceutical
      ingredient (API) and a polymer stabilizer. A solution of API and polymer
      excipient(s) is spread on a cold solid surface to form a thin film that freezes
      in 50 ms to 1s. This study provides an understanding of how the solvent's
      physical properties and the thin film geometry influence the freezing rate and
      consequently the final physico-chemical properties of URF-processed powders.
      Theoretical calculations of heat transfer rates are shown to be in agreement with
      infrared images with 10ms resolution. Danazol (DAN)/polyvinylpyrrolidone (PVP)
      powders, produced from both acetonitrile (ACN) and tert-butanol (T-BUT) as the
      solvent, were amorphous with high surface areas (approximately 28-30 m2/g) and
      enhanced dissolution rates. However, differences in surface morphology were
      observed and attributed to the cooling rate (film thickness) as predicted by the
      model. Relative to spray-freezing processes that use liquid nitrogen, URF also
      offers fast heat transfer rates as a result of the intimate contact between the
      solution and cold solid surface, but without the complexity of cryogen
      evaporation (Leidenfrost effect). The ability to produce amorphous high surface
      area powders with submicron primary particles with a simple ultra-rapid freezing
      process is of practical interest in particle engineering to increase dissolution
      rates, and ultimately bioavailability.

PMID- 16987643
TI  - Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine:
      a systematic review.
AB  - The objective of this review was to evaluate the strength of evidence of
      effectiveness for Petasites hybridus in the prophylaxis of migraine. Several
      databases and other sources were searched to identify randomised-controlled
      trials investigating P. hybridus preparations. Two trials totalling 293 patients
      (60 and 233 patients) were included in this review. Both trials investigated the
      proprietary Petasites root extract Petadolex. The trials were described in
      narrative way, taking into consideration methodological quality scores. Pooling
      of data was not carried out due to the heterogeneity of the results. The extract
      at higher dose (150 mg) showed a greater decreased frequency of migraine attacks
      and a greater number of responders (improvement>50%) after treatment over 3-4
      months than the extract at lower dose (100 mg) and placebo. Moderate evidence of
      effectiveness is, thus, available for a higher than the recommended dose of the
      proprietary Petasites root extract Petadolex in the prophylaxis of migraine.
      Further rigorous studies are required to confirm effectiveness and safety in long
      term use before treatment with Petasites root extract can be recommended as an
      alternative option in the treatment schedule for the prophylaxis of migraine.

PMID- 16987644
TI  - Activity of 7-methyljuglone in combination with antituberculous drugs against
      Mycobacterium tuberculosis.
AB  - The recent increase in the incidence of tuberculosis with the emergence of
      multidrug-resistant (MDR) cases has lead to the search for new drugs that are
      effective against MDR strains of Mycobacterium tuberculosis and can augment the
      potential of existing drugs against tuberculosis. In the present study, we
      investigated the activities of a naphthoquinone, 7-methyljuglone, isolated from
      the roots of Euclea natalensis alone and in combination with other
      antituberculous drugs against extracellular and intracellular M. tuberculosis.
      Combinations of 7-methyljuglone with isoniazid or rifampicin resulted in a four
      to six-fold reduction in the minimum inhibitory concentration of each compound.
      Fractional inhibitory concentration (FIC) indexes obtained were 0.2 and 0.5,
      respectively, for rifampicin and isoniazid, suggesting a synergistic interaction
      between 7-methyljuglone and these anti-TB drugs. The ability of 7-methyljuglone
      to enhance the activity of isoniazid and rifampicin against both extracellular
      and intracellular organisms suggests that 7-methyljuglone may serve as a
      promising compound for development as an anti-tuberculous agent.

PMID- 16987645
TI  - Clinical review: idiopathic pulmonary fibrosis--past, present and future.
AB  - Idiopathic pulmonary fibrosis (IPF) is an important, and devastating,
      interstitial lung disease. It has a median mortality of only 3 years, worse than
      many cancers, and its incidence continues to rise. In this article, an overview
      of key developments in our understanding and clinical management of IPF will be
      provided.

PMID- 16987646
TI  - Networking possibilities for waste recycling in Miyagi prefecture, Japan.
AB  - Successful case studies for waste recycling in Japan have not been evaluated. The
      evaluation of economic efficiency and environmental effects were lacking at the
      time the actual network was established. A waste/resource input/output (I/O)
      coincidence retrieval system called ZENESYS was developed to examine the
      usefulness of a waste-exchange network in a nonmanufacturing district. We
      analyzed data from the Miyagi prefecture, a region without heavy industry. The
      data were collected from 77 companies using a questionnaire and interviews. A
      total of 33 possible waste exchange links arose after analysis using ZENESYS.
      However, these were frail networks that relied heavily on the construction
      industry. Two waste recycling technologies were selected from the ZENESYS
      database: reclaiming fuel from waste plastic and making construction materials
      from bottom ash. Evaluation of the environmental effects and economics of these
      two technologies showed they were both suitable for the environment, but no
      profit was made from reclaiming fuel from waste plastics. We concluded that in an
      area with no heavy industry, it may be difficult to adopt recycling technologies
      that have high environmental and economic performance. Materials are difficult to
      circulate among manufacturing industries even if a waste-exchange network exists,
      and resources are consumed during transportation and recycling.

PMID- 16987647
TI  - A case study of waste management at the Northern Finnish pulp and paper mill
      complex of Stora Enso Veitsiluoto Mills.
AB  - This work presents the current waste management system at the pulp and paper mill
      complex of Stora Enso Oyj Veitsiluoto Mills at Kemi, Northern Finland. This paper
      covers examples of case studies carried out at the mill and describes how the
      wastes and by-products are utilized as a neutralizing agent for acidic
      wastewaters (i.e., green liquor dregs from the causticizing process), as a
      hardener in filling mine cavities (i.e., ash from the fluidized bed boiler), as a
      landscaping agent (i.e., ash as well as the fibre clay from chemical wastewater
      treatment plant), as a hydraulic barrier material for landfills (i.e., fibre
      clay), and as a soil enrichment agent (i.e., calcium carbonate from the
      precipitated calcium carbonate plant). In addition, the wood waste from the wood
      handling plant, sawmill, packaging pallet plant and from the groundwood mill, as
      well as the biosludge from the biological wastewater treatment plant, are all
      incinerated in the fluidized bed boiler for energy production. Due to effective
      utilization of the solid wastes generated at the mills, the annual amount of
      waste to be disposed of in the landfill has decreased between 1994 and 2004 from
      42,990 to 6083 tonn (expressed as wet weight). The paper also gives an overview
      of the relevant European Union legislation on the forest industry and on waste
      management, as well as of the pulping process and of the generation of major
      solid wastes in the pulp and paper mills.

PMID- 16987648
TI  - Predicted performance of clay-barrier landfill covers in arid and semi-arid
      environments.
AB  - Conventional landfill cover systems for municipal solid waste include low
      permeability compacted clay barriers to minimize infiltration into the landfilled
      waste. Such layers are vulnerable in climates where arid to semi-arid conditions
      prevail, whereby the clay cover tends to desiccate and crack, resulting in
      drastically higher infiltration, i.e., lower cover efficiency. To date, this
      phenomenon, which has been reported in field observations, has not been
      adequately assessed. In this paper, the performance of a cover system solely
      relying on a clay barrier was simulated using a numerical finite element
      formulation to capture changes in the clay layer and the corresponding modified
      hydraulic characteristics. The cover system was guided by USEPA Subtitle-D
      minimum requirements and consisted of a clay layer underlying a protective
      vegetated soil. The intrinsic characteristics of the clay barrier and vegetative
      soil cover, including their saturated hydraulic conductivities and their soil
      water characteristic curves, were varied as warranted to simulate intact or
      "cracked" conditions as determined through the numerical analyses within the
      proposed methodology. The results indicate that the levels of percolation through
      the compromised or cracked cover were up to two times greater than those obtained
      for intact covers, starting with an intact clay hydraulic conductivity of 10(
      5)cm/s.

PMID- 16987649
TI  - DNA detection system using molecularly imprinted polymer as the gel matrix in
      electrophoresis.
AB  - To develop a simple and inexpensive method for DNA detection, we prepared a
      molecularly imprinted polymer (MIP) for recognizing a specific double-stranded
      DNA (dsDNA) sequence and used it in an electrophoretic gel matrix. The MIP gel
      has many binding sites that are complementary in size, shape, and arrangement of
      functional groups of the target dsDNA sequence. During MIP gel electrophoresis
      (MIPGE), migration of the target dsDNA should be hindered by the capture effect
      of the binding sites in the MIP gel. This was confirmed by observation of
      deviations from the linear relationship between the migration distances of the
      DNA standard size markers in the polyacrylamide gel and those in the MIP gel. The
      migration distances of nontarget dsDNA maintained a linear relationship, however.
      In addition, the sequence selectivity of dsDNA in this method was investigated by
      using the Ha-ras gene and its point mutants. Except for A.T to T.A base pair
      substitution, mutant dsDNA (for example, substitution from A.T to C.G and from
      G.C to T.A) could be distinguished from the target (wild-type) dsDNA. Although
      some improvement in A.T (T.A) base pair distinction is still needed, this study
      is the first to demonstrate detection of a specific dsDNA sequence with MIPs and,
      as such, opens up a new realm for practical applications of MIPs.

PMID- 16987650
TI  - Development of a self-sterilizing lancet coated with a titanium dioxide
      photocatalytic nano-layer for self-monitoring of blood glucose.
AB  - A photocatalyst was applied to a lancet for pricking the finger to obtain an
      antibacterial property. A photocatalytic and uniform nano-layer of titanium
      dioxide (TiO2) on the surface of the lancet (0.36 mm x 24.5 mm) was formed by
      sputtering and annealed for crystallization of the TiO2 layer. By elementary
      analysis of the TiO2 layer, titanium and oxygen were detected. Next, for the
      estimation of the antibacterial properties resulting from the photocatalytic
      effect, the lancet was packed into a capillary tube filled with a suspension of
      Escherichia coli K-12 (non-spore-forming bacterium), and was continuously rolled
      in a continuous UV-irradiation system under black-light irradiation. Distinct
      antibacterial effects after irradiation at 0.5 mW cm(-2) for 45 min were observed
      in the crystallized TiO2 layer on the lancet. Finally, lancing resistances
      obtained by pricking an artificial skin sheet were examined using control
      lancets, and lancets with an unannealed TiO2 layer or an annealed TiO2 layer. The
      results showed almost the same lancing resistances for the control (0.53+/-0 N,
      n=3) and the lancet with an annealed TiO2 layer (0.51+/-0.018 N), while the
      lancet with an unannealed TiO2 layer showed a high lancing resistance compared
      with the other lancets (0.62+/-0.05 N). In conclusion, the lancet coated with a
      crystallized, velvety nano-layer of TiO2 obtained by annealing had antibacterial
      properties and a similar lancing resistance compared with the bare lancet, and
      showed potential for application in monitoring blood glucose in diabetes.

PMID- 16987652
TI  - New technologies.

PMID- 16987653
TI  - Health-related quality of life and adverse late effects in adult (very) long-term
      childhood cancer survivors.
AB  - PURPOSE:  METHOD: The RAND-36 was used to assess HRQoL in all adult (> or =18
      years) survivors who had attended the long-term follow-up clinic since 1995. The
      survivors were divided into two groups based on the length of follow-up: Group LF
      (long term follow-up, follow-up > or =20 years, n=129) and Group VLF (very long
      term follow-up, follow-up >20 years, n=184). Data on diagnosis, treatment and
      complications were obtained from medical records. Late effects were graded using
      the CTCAEv3. RESULTS: The RAND-36 was completed by 313 (86.2%) out of 363
      eligible patients. Except for higher scores on the subscale Bodily pain, LF
      patients did not differ significantly on the RAND-36 subscales from the
      population sample; VLF patients had significant lower scores on the subscales
      Physical functioning (P=0.003), Social functioning, Vitality and General health
      perception (P<0.001). Significantly more VLF patients (P<0.001) had severe (grade
      3 and 4) late effects (47.8%) compared to LF patients (27.9%). Female gender and
      especially psycho-social late effects were inversely related to HRQoL.
      CONCLUSION: Childhood cancer survivors who were diagnosed more than 20 years ago
      have lower scores on the RAND 36, and have significantly more severe late effects
      than those diagnosed more recently. Patients with longer follow-up are more
      likely to become lost to follow-up. Time has come to establish new models of care
      for adult childhood cancer survivors, which are more flexible and appropriate to
      the needs of adult childhood cancer survivors.

PMID- 16987654
TI  - Did you skip the lectures?

PMID- 16987655
TI  - Clinical heart failure in a cohort of children treated with anthracyclines: a
      long-term follow-up study.
AB  - The cumulative incidence of anthracycline-induced clinical heart failure (A-CHF)
      in a large cohort of 830 children treated with a mean cumulative anthracycline
      dose of 288 mg/m2 (median 280 mg/m2; range 15-900 mg/m2) with a very long and
      complete follow-up after the start of anthracycline therapy (mean 8.5 years;
      median 7.1 years; range 0.01-28.4 years) was 2.5%. A cumulative anthracycline
      dose of 300 mg/m2 or more was the only independent risk factor (relative risk
      (RR)=8). The estimated risk of A-CHF increased with time to 5.5% at 20 years
      after the start of anthracycline therapy; 9.8% if treated with 300 mg/m2 or more.
      In conclusion, 1 in every 10 children treated with a cumulative anthracycline
      dose of 300 mg/m2 or more will eventually develop A-CHF. This is an extremely
      high risk and it reinforces the need of re-evaluating the cumulative
      anthracycline dose used in different treatment protocols and to define strategies
      to prevent A-CHF which could be implemented in treatment protocols.

PMID- 16987656
TI  - Biodegradation of chlorferon and diethylthiophosphate by consortia enriched from
      waste cattle dip solution.
AB  - Chlorferon and diethylthiophosphate (DETP) are the hydrolysis products of
      coumaphos, an organophosphate pesticide. In this research, two consortia of
      bacterial cultures, one responsible for degrading chlorferon and the other for
      degrading DETP, were selectively enriched from waste cattle dip solution. The
      enriched cultures were used as inocula to grow biomass for biodegradation
      studies. For chlorferon degradation, the optimum biomass concentration was found
      to be 80g/L, and pH 7.5 was selected as the optimal operating pH. Chlorferon
      degradation was characterized by substrate inhibition kinetics with parameter
      values estimated to be V(m)=0.062+/-0.011mg/(g-biomass)h, K(m)=21+/-7mg/L, and
      K(Si)=118+/-45mg/L. For DETP degradation, the optimum biomass concentration was
      found to be 60g/L, and the optimum pH was in the range of 7.5-8. DETP degradation
      was characterized by Michaelis-Menten kinetics with parameter values estimated to
      be V(m)=1.52+/-0.10mg/(g-biomass)h and K(m)=610+/-106mg/L.

PMID- 16987657
TI  - A series of novel, potent, and selective histone deacetylase inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer
      therapy and the first generation HDAC inhibitors are currently in clinical
      trials. A structurally novel series of HDAC inhibitors based on the natural
      cyclic tetrapeptide Apicidin is described. Selected screening of the sample
      collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives
      identified a small acyclic lead molecule 1 with the unusual ketone zinc binding
      group. SAR studies around this lead resulted in optimization to potent, low
      molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to
      current clinical candidates.

PMID- 16987658
TI  - New rifabutin analogs: synthesis and biological activity against Mycobacterium
      tuberculosis.
AB  - The synthesis, structure, and biological evaluation of a series of novel
      rifamycin derivatives, Rifastures (RFA) with potent anti-tuberculosis activity
      are presented. Some of these derivatives showed higher in vitro activity than
      rifabutin and rifampicin against not only Mycobacterium tuberculosis strains but
      also against MAC and Mycobacterium kansasii.

PMID- 16987659
TI  - Metal complexes with superoxide dismutase-like activity as candidates for anti
      prion drug.
AB  - Various compounds were evaluated for ability to inhibit the formation of the
      abnormal protease-resistant form of prion protein (PrP-res) in two cell lines
      infected with different prion strains. Examination of the structure-activity
      relationships indicated that compounds with copper-selective chelating ability
      and whose copper complexes have high SOD-like activity are candidates for anti
      prion drug.

PMID- 16987660
TI  - Hydroxyl radicals scavenging activity of N-substituted chitosan and quaternized
      chitosan.
AB  - N-substituted chitosan and quaternized chitosan were synthesized and their
      antioxidant activity against hydroxyl radicals was assessed, respectively.
      Compared with the antioxidant activity of chitosan, the results indicated that
      the two kinds of chitosan derivatives had different scavenging ability on
      hydroxyl radicals, which should be related to the form of amido in the two kinds
      of chitosan derivatives.

PMID- 16987661
TI  - Synthesis and activity of novel bile-acid conjugated glucocorticoid receptor
      antagonists.
AB  - A series of potent steroidal glucocorticoid receptor antagonists has been
      discovered. After conjugation to cholic acid, the compounds retained an affinity
      for GR in vitro and had modest in vivo efficacy.

PMID- 16987662
TI  - Synthesis and SAR of GlyT1 inhibitors derived from a series of N-((4-(morpholine
      4-carbonyl)-1-(propylsulfonyl)piperidin-4-yl)methyl)benzamides.
AB  - This Letter describes the synthesis and SAR, developed through an iterative
      analog library approach, of potent and selective non-sarcosine-derived GlyT1
      inhibitors.

PMID- 16987663
TI  - Oncoplastic fellowship: can we do better?

PMID- 16987664
TI  - Posttranslational modifications of NEMO and its partners in NF-kappaB signaling.
AB  - NEMO, the regulatory subunit of the IkappaB kinase (IKK) complex that controls
      the activation of the transcription factor NF-kappaB, is required for IKK
      function in most situations, but its exact mode of action has remained elusive
      until recently. A series of publications now provides information about how
      posttranscriptional modifications of NEMO, such as ubiquitination, sumoylation or
      phosphorylation, regulate its function in the IKK complex. These modifications
      might also regulate a cytosolic pool of free NEMO that controls the activation of
      NF-kappaB induced by genotoxic stress. Together with a better identification of
      the modifications controlling partners of NEMO, a clearer picture of how IKK
      becomes activated upon cell stimulation is starting to emerge, providing new
      clues for how the NF-kappaB pathway could be modulated for therapeutic purposes.

PMID- 16987665
TI  - The feasibility of a video-based motion analysis system in measuring the
      segmental movements between upper and lower cervical spine.
AB  - The evaluation of the range of motion (ROM) and static posture in the cervical
      spine are important in physical examination. Despite offering dynamic assessment
      without radiation, the video-based motion analysis system has not yet been
      applied to measure the cervical segmental movements. The purposes of this study
      were to develop a neck model to differentiate the movements and posture between
      upper and lower cervical spine, and to examine the reliability of measuring
      cervical motion with surface markers and the aid of videofluoroscopy. Sixteen
      healthy adult subjects (eight males and eight females) participated in this
      study. Ten surface markers were used to estimate the discrepancies in cervical
      vertebral angles compared with corresponding bony landmarks throughout the ROM.
      The average intraclass correlation coefficients (ICCs) of the paired vertebral
      angles between surface markers and bony landmarks ranged from 0.844 to 0.975 and
      the mean absolute difference (MAD) averaged 2.96 degrees. Our results indicate
      high consistency between surface markers and bony landmarks throughout the
      cervical movements. The mean upper (C0-C2) and lower (C2-C7) cervical joint
      angles in the neutral position were 18.59+/-4.33 degrees and 23.98+/-6.15
      degrees, respectively. Furthermore, the reliability of the digitizing procedure
      within raters (ICC=0.850-0.999; MAD=0.58-2.42 degrees) and between raters
      (ICC=0.759-0.988; MAD=0.59-2.66 degrees) suggests that the neck motion analysis
      model is a feasible method for investigating static neck posture or dynamic
      motion between upper and lower cervical spine.

PMID- 16987667
TI  - A method for calculation of true coincidence summing correction factors for
      extended sources.
AB  - In gamma-ray spectrometry, true coincidence summing correction factors for an
      extended sample can be calculated from full-energy-peak and total efficiencies as
      if the sample were a point source, if the so-called linear-to-square- (LS) curve,
      introduced by Blaauw and Gelsema, is known and properly applied. A method is
      described for obtaining the efficiencies and the corresponding LS-curve for an
      arbitrary cylindrical sample from calibration measurements in a reference
      geometry. The approach is aimed at the analysis of samples measured on p-type
      HPGe detectors in environmental gamma-ray spectrometry and was successfully
      verified against experimental data.

PMID- 16987666
TI  - Pyrrolo[2,3-h]quinolinones: a new ring system with potent photoantiproliferative
      activity.
AB  - A new class of compounds, the pyrrolo[2,3-h]quinolin-2-ones, nitrogen isosters of
      the angular furocoumarin Angelicin, was synthesized with the aim of obtaining new
      photochemotherapeutic agents with increased antiproliferative activity and lower
      undesired toxic effects than the lead compound. Two synthetic pathways were
      approached to allow the isolation both of the dihydroderivatives 10-17 and of the
      aromatic ring system 23. Compounds 10-17 showed a remarkable phototoxicity and a
      great UVA dose dependence reaching IC(50) values at submicromolar level.
      Intracellular localization of these compounds has been evaluated by means of
      fluorescence microscopy using tetramethylrhodamine methyl ester and acridine
      orange, which are specific fluorescent probes for mitochondria and lysosomes,
      respectively. A weak co-staining was observed with mitochondrial stain, whereas a
      specific localization in lysosomes was observed. Studies directed to elucidate
      the mode of action of this series of compounds revealed that they do not
      intercalate with DNA and do not induce photodamage to the macromolecule. On the
      contrary, they induce significative photodamage to lipids and proteins.

PMID- 16987668
TI  - Olfactory ensheathing glia graft in combination with FK506 administration promote
      repair after spinal cord injury.
AB  - The aim of this study was to determine whether a combination of olfactory
      ensheathing cell (OEC) graft with the administration of FK506, two experimental
      approaches that have been previously reported to exert protective/regenerative
      effects after spinal cord injury, promotes synergic restorative effects after
      complete or partial spinal cord injuries. In partial spinal cord injury,
      combination of an OEC graft and FK506 reduced functional deficits evaluated by
      the BBB score, motor-evoked potentials (MEPs) and H reflex tests, diminished
      cavitation, astrogliosis and increased sparing/regeneration of raphespinal fibers
      compared to untreated and single-treatment groups of rats. After complete spinal
      cord transection, the combined treatment significantly improved functional
      outcomes, promoted axonal regeneration caudal to the lesion, and diminished
      astrogliosis compared only to non-transplanted animals. Slightly, but non
      significant, better functional and histological results were found in OEC-grafted
      animals treated with FK506 than in those given saline after spinal cord
      transection. Nevertheless, the combined treatment increased the percentage of
      rats that recovered MEPs and promoted a significant reduction in astrogliosis. In
      conclusion, this study demonstrates that OEC grafts combined with FK506 promote
      additive repair of spinal cord injuries to those exerted by single treatments,
      the effect being more remarkable when the spinal cord is partially lesioned.

PMID- 16987669
TI  - Synthesis and cellular studies of PEG-functionalized meso-tetraphenylporphyrins.
AB  - The total syntheses of four PEG-functionalized porphyrins, containing one to four
      low molecular weight PEG chains linked via amide bonds to the para-phenyl
      positions of meso-tetraphenylporphyrin, are reported. The hydrophobic character
      of the PEG-porphyrins decreases with the number of PEG chains linked to the
      porphyrin ring, while their tendency for aggregation in buffered aqueous solution
      increases. The porphyrins containing one or two PEG chains accumulated within
      human HEp2 cells to a much higher extent than those having three or four PEGs at
      the macrocycle periphery. All PEG-porphyrins were found to be non-toxic in the
      dark, and only those containing one or two PEG chains were phototoxic (IC(50)=2
      microM at 1J/cm(2) light dose). The preferential sites of subcellular
      localization of the porphyrins containing one or two PEG chains were found to be
      the mitochondria and endoplasmic reticulum (ER), while those containing three or
      four PEG chains localize preferentially in the lysosomes.

PMID- 16987670
TI  - Molecular cloning, characterization and expression analysis of an IL-21 homologue
      from Tetraodon nigroviridis.
AB  - Interleukin-21 (IL-21) is an important immune cytokine that was well
      characterized in human and mammals, but little is known in fish. In present
      study, an IL-21 homologue was cloned and well characterized from Tetraodon
      nigroviridis. The full-length Tetraodon IL-21 cDNA was 849bp in size, containing
      an open reading frame (ORF) of 438bp that translated a 145 amino-acid peptide, a
      5' untranslated region (UTR) of 69bp, and a 3' UTR of 342bp. The deduced peptide
      shared identity of 20-49% with other known IL-21 sequences. The Tetraodon IL-21
      gene had six exons while both human and Takifugu IL-21 gene contained only five
      exons. However, the level of synteny between human, Takifugu and Tetraodon
      genomes was well conserved during evolution. In vivo expression study showed that
      Tetraodon IL-21 mRNAs were constitutively expressed at a low level and only in
      limited tissues, including gut, gill and gonad in healthy fish, and stimulation
      with LPS increased the expression of IL-21 in these tissues and induced the
      expression of IL-21 in kidney, spleen and skin, indicating that IL-21 is an
      inflammatory stress inducible gene associated with the anti-bacterial defense in
      fish. Our study provided further evidence for the existence of IL-21 in fish, and
      gained further insight into the immunological functions of IL-21 gene in fish.

PMID- 16987671
TI  - A novel method for improvement of visualization of power spectra for sorting cryo
      electron micrographs and their local areas.
AB  - In a context of automation of cryo-electron microscopy, we developed a novel
      method for improving visibility of diffraction rings in the power spectra of cryo
      electron micrographs of vitreous ice (without carbon film or high concentration
      of diffracting material). We used these enhanced spectra to semi-automatically
      detect and remove micrographs and/or local areas introducing errors in the global
      3D map (drifted and charged areas) or those unable to increase global signal-to
      noise ratio (non-diffracting areas). Our strategy also allows a detection of
      micrographs/areas with a strong astigmatism. These images should be removed when
      using algorithms that do not correct astigmatism. Our sorting method is simple
      and fast since it uses the normalized cross-correlation between enhanced spectra
      and their copies rotated by 90 degrees. It owes its success mainly to the novel
      pre-processing of power spectra. The improved visibility also allows an easier
      visual check of accuracy of sorting. We show that our algorithm can even improve
      the visibility of diffraction rings of cryo-electron micrographs of pure water.
      Moreover, we show that this visibility depends strongly on ice thickness. This
      algorithm is implemented in the Xmipp (open-source image processing package) and
      is freely available for implementation in any other software package.

PMID- 16987672
TI  - Electron energy filtering significantly improves amplitude contrast of frozen
      hydrated protein at 300kV.
AB  - The amplitude contrast of frozen-hydrated biological samples was measured using
      the bacterial flagellar filament embedded in vitreous ice at an accelerating
      voltage of 300kV. From the mean radial amplitude spectra of overfocused images,
      amplitude contrast was estimated to be 6.9+/-1.9% and 2.7+/-1.0% of the whole
      contrast at the low spatial frequency range with and without energy filtering,
      respectively, and that of the carbon film to be 9.5+/-2.0% and 5.8+/-1.8%. Energy
      filtering effectively doubled the signal-to-noise ratio in the images of frozen
      hydrated filaments, and substantially improved intensity data statistics of layer
      lines up to at least approximately 25A resolution in their Fourier transforms. It
      also markedly improved inter-particle fitting phase residuals of averaged data at
      resolutions up to approximately 15A. Using the energy filtered data recorded on a
      new high-performance, lens-coupled CCD camera the three-dimensional map of the
      flagellar filament was calculated at 8A by applying the amplitude contrast of
      6.9%. The map and its mean radial density distribution validated the obtained
      value of the amplitude contrast.

PMID- 16987673
TI  - Traces of vocabulary acquisition in the brain: Evidence from covert object
      naming.
AB  - One of the strongest predictors of the speed with which adults can name a
      pictured object is the age at which the object and its name are first learned.
      Age of acquisition also predicts the retention or loss of individual words
      following brain damage in conditions like aphasia and Alzheimer's disease.
      Functional Magnetic Resonance Imaging (fMRI) was used to reveal brain areas
      differentially involved in naming objects with early or late acquired names. A
      baseline task involved passive viewing of non-objects. The comparison between the
      silent object naming conditions (early and late) with baseline showed significant
      activation in frontal, parietal and mediotemporal regions bilaterally and in the
      lingual and fusiform gyri on the left. Direct comparison of early and late items
      identified clusters with significantly greater activation for early acquired
      items at the occipital poles (in the posterior parts of the middle occipital
      gyri) and at the left temporal pole. In contrast, the left middle occipital and
      fusiform gyri showed significantly greater activation for late than early
      acquired items. We propose that greater activation to early than late objects at
      the occipital poles and at the left temporal pole reflects the more detailed
      visual and semantic representations of early than late acquired items. We propose
      that greater activation to late than early objects in the left middle occipital
      and fusiform gyri occurs because those areas are involved in mapping visual onto
      semantic representations, which is more difficult, and demands more resource, for
      late than for early items.

PMID- 16987674
TI  - To press or not to press? Differential receptor expression and response to
      novelty in rats learning an operant response for reward.
AB  - Learning to perform instrumental tasks is an ability of all animals. In a
      population of rats, not all individuals will acquire an operant response for
      reward. We hypothesized that there could be a genetic explanation for differences
      between High Consumers (those that acquired the lever press response) and Low
      Consumers (lever press response is low). Additionally, we proposed that this
      genetic difference could produce measurable changes in response to novelty.
      Wistar rats were trained to lever press for a 0.2% saccharin reward and on the
      10th day they were placed in a novel open field for 30 min to record locomotor
      activity. The prefrontal cortex and hippocampus were dissected and qPCR was used
      to measure mRNA expression. A significant difference (p=.048; 2-way ANOVA) in
      gene expression was observed between Low and High Consumers. A principal
      component analysis (PCA), to cluster which genes represent this difference,
      identified 4 genes; 5-HT2A and mGlu1 in the hippocampus and AMPA GluR1 and
      adrenergic alpha2A in the prefrontal cortex. Response to a novel open field also
      differed since Low Consumers displayed a higher Total Distance in comparison to
      High Consumers. Additionally, Low Consumers could be subdivided into Low-Lever
      (with lever press response only when water deprived) and Low-Non-Lever (lever
      press response is low throughout training). PCA with this subdivision identified
      an additional nine genes differing within the divisions; NMDA NR2B and
      GABAAalpha3 in the prefrontal cortex and adrenergic alpha2B and alpha2A, AMPA
      GluR1, GluR2 and GluR3, 5-HT1B and GABAAalpha5 in the hippocampus.

PMID- 16987675
TI  - Opposite effects of a single versus repeated doses of gabapentin on retention
      performance of an inhibitory avoidance response in mice.
AB  - CF-1 male mice were trained in an inhibitory avoidance (IA) task. A single
      gabapentin (GBP) administration (50mg/kg, ip) immediately after training enhanced
      retention performance when mice were tested 8 days after training. On the
      contrary, when the same dose of the anticonvulsant drug was given twice a day for
      7 days (repeated treatment), a significant impairment on retention performance
      12h after the last injection of GBP was observed. When the retention test was
      delayed 7 days after the end of the repeated treatment, the retention performance
      was not significant different from the control group, whereas if the retention
      test was delayed 14 days, retention performance was higher than control group but
      similar to that observed when GBP was administered once immediately after
      training. The impairment on retention performance was correlated with a
      significant decrease in the high affinity choline uptake in the hippocampus at
      the end of the retention test. The pretest administration of the direct
      muscarinic cholinergic agonist oxotremorine (50 microg/kg, ip) reversed the
      impairment on retention performance. This reversion was prevented by the
      muscarinic cholinergic antagonist scopolamine (0.5 mg/kg, ip). Taken together,
      these results suggest that the impairment on retention performance of an IA task
      in mice induced by repeated administration of GBP affected memory retrieval but
      not memory consolidation and that this impairment may be attributable to a
      reduction on central cholinergic activity.

PMID- 16987676
TI  - Haptic applications for molecular structure manipulation.
AB  - We describe the application of haptic technology to enhance the information
      available in chemical systems, specifically related to computational drug design.
      These methods are designed to build upon the visual information presented by
      molecular viewers and add the sensation of touch, or force feedback. The addition
      of sensory input can aid in the analysis of molecular structures and the
      understanding of intermolecular interactions by delivering chemically relevant
      forces to the end user.

PMID- 16987677
TI  - Polar cod, Boreogadus saida (Gadidae), show an intermediate stress response
      between Antarctic and temperate fishes.
AB  - To examine whether the attenuated stress response observed in Antarctic
      notothenioid fishes is a specialism for life in sub-zero waters, the polar cod,
      Boreogadus saida, and the temperate shorthorned sculpin, Myoxocephalus scorpius,
      were subjected to various stress treatments. Activity stress in both species had
      no effect on plasma catecholamine and cortisol levels, splenic mass, and on the
      haematological variables in B. saida. In contrast, heat stress caused a
      significant rise in circulating noradrenaline and adrenaline levels in B. saida,
      accompanied by a significant increase in haematocrit and haemoglobin
      concentrations, at constant plasma cortisol levels, red blood cell count and
      splenic mass. A concomitant rise in blood lactate concentrations indicated that
      heat-stressed B. saida were hypoxaemic. The capacity to synthesise catecholamines
      in B. saida was 38% of the value in M. scorpius, but similar to the values for
      Antarctic notothenioids. The lack of any adrenergic response to activity stress
      suggests that dominance of cholinergic control of the cardiovascular system may
      not be restricted to Antarctic notothenioids. Rather, the stress response in B.
      saida appears to be intermediate between Antarctic and temperate teleosts, in
      keeping with their relatively recent occupation of cold Arctic waters.

PMID- 16987678
TI  - [Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and
      secondary resection].
AB  - Induction chemoradiotherapy (CRT) may downstage locally advanced pancreatic
      tumors but secondary resections are unfrequent. However some responders' patients
      may benefit of a R0 resection. PATIENTS AND METHODS: We report 18 resections
      among 29 locally advanced pancreatic cancers; 15 patients were treated with
      neoadjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients)
      chemoradiotherapy (45 Gy), and 3 patients without histologically proven
      adenocarcinoma were resected without any preoperative treatment. RESULTS: The
      morbidity rate was 28% and the mortality rate was 7%; one patient died after
      resection (5.5%) and one died after exploration (9%). The R0 resection rate was
      50%. The median survival for the resected patients was not reached and the
      actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and
      the two patients were alive at 15 and 46 months without recurrence; one specimen
      showed less than 10% viable tumoral cells and the patient was alive at 36 months
      without recurrence. A mesenteric infarction was the cause of a late death at 3
      years in a disease free patient (radiation induced injury of the superior
      mesenteric artery). The median survival of the 11 non-resected patients was 21
      months and the actuarial survival at 2 years was 0%. When the number of the
      resected patients (18) was reported to the entire cohort of the patients with
      locally advanced pancreatic cancer treated during the same period in our
      institution, the secondary resectability rate was 9%. CONCLUSION: Preoperative
      chemoradiotherapy identifies poor surgical candidates through observation and may
      enhance the margin status of patients undergoing secondary resection for locally
      advanced tumors. However it remains difficult to evaluate the results in the
      literature because of the variations in the definitions of resectability. The
      best therapeutic strategy remains to be defined, because the majority of patients
      ultimately succumb with distant metastatic disease.

PMID- 16987679
TI  - [Conservative and functional management for soft tissue sarcomas of the
      extremities: role of radiotherapy].
AB  - Recent publications have permitted to quantify the benefit of radiotherapy in the
      conservative treatment of soft tissue sarcoma of the limbs. The aim of this
      review is to focus on aspects of radiotherapy witch influence local control and
      functional outcome for early and late normal tissue damage. The evaluation of
      late effects is performed according to Soma-Lent (Subjective-Objective-Management
      Analytic-Late Effects of Normal Tissues) classification. About complications,
      neurological complications are probably under estimated and are related to total
      dose of radiation therapy.

PMID- 16987680
TI  - Predominant cervical involvement in patients with psoriatic arthritis: report of
      two cases.
AB  - Cervical spine involvement is common but usually delayed in patients with
      psoriatic arthritis. We report two cases with early and predominant involvement
      of the upper cervical spine. Synovitis of the atlanto-odontoid joint and fusion
      of multiple facet joints were noted in one patient. In the other patient, the
      main finding was atlanto-axial subluxation with erosions of the odontoid process
      and anterior arch of C1. No abnormalities were noted in the peripheral joints,
      sacroiliac joints, or thoracolumbar spine. Analgesics and conventional
      antiinflammatory agents were only minimally effective. TNFalpha antagonist
      therapy (infliximab followed by etanercept) in one patient and phenylbutazone
      therapy in the other improved the symptoms and led to shrinkage of the pannus.

PMID- 16987681
TI  - Expression of CXCR-1 and CXCR-2 chemokine receptors on synovial neutrophils in
      inflammatory arthritides: does persistent or increasing expression of CXCR-2
      contribute to the chronic inflammation or erosive changes?
AB  - OBJECTIVE: To analyze the CXCR-1 and CXCR-2 chemokine receptor expression on
      peripheral blood neutrophils (PBN) and synovial fluid neutrophils (SFN) of
      patients with rheumatoid arthritis (RA) and Behcet's disease (BD) (characterized
      by erosive and non-erosive arthritis, respectively), and to compare them with
      those of patients with osteoarthritis (OA). METHODS: We used flow cytometry to
      investigate the expression of CXCR-1 and CXCR-2 chemokine receptors on PBN and
      SFN of fifty-five (22 RA, 22 BD and 11 OA) age and sex-matched patients. RESULTS:
      In respect to chemokine receptor expression on neutrophils isolated from patients
      with RA, mean fluorescein intensity (MFI) of CXCR-1 chemokine receptors on PBN
      from active and inactive RA patients, and SFN from patients with RA were 151 (90
      395), 129 (81-539) and 136 (64-220), respectively, and there were not
      statistically significant difference each other. But MFI of CXCR-2 chemokine
      receptors on SFN of patients with RA was 18 (10-32), and significantly higher
      than PBN of active and inactive RA patients (MFI: 10 (6-15) and 12 (7-16),
      P=0.002 and 0.037, respectively). In respect to chemokine receptor expression on
      neutrophils isolated from patients with BD, MFI of CXCR-1 chemokine receptors on
      PBN of active BD patients was 245 (97-844), and higher than PBN of active RA
      patients and SFN of BD patients (MFI: 151 (90-395) and 134 (61-231), P=0.047 and
      0.017, respectively). MFI of CXCR-2 chemokine receptors on PBN of active and
      inactive BD patients, and SFN of patients BD were 10 (6-14), 10 (2-16), and 12 (8
      24), respectively, there were not statistically significant difference each
      other. MFI of CXCR-1 chemokine receptors on SFN from patients with RA, BD, and OA
      were 136 (64-220), 134 (61-231), and 114 (60-180), respectively, and there was no
      difference between the study groups. MFI of CXCR-2 chemokine receptors on SFN of
      patients with RA was 18 (10-32), and higher than patients with BD and OA (MFI: 12
      (8-24) and 11 (9-18), P=0.037 and 0.005, respectively), though there was no
      difference between last two groups. CONCLUSION: Our study points that CXCR-1 and
      CXCR-2 chemokine receptors of SFN may have diverse functions in the course of
      inflammatory arthritides. These results indicate that CXCR-2 chemokine receptor
      might play more critical role in long lasting accumulation of neutrophils within
      the synovial fluid of patients with RA.

PMID- 16987682
TI  - Medical management of patients over 50 years admitted to orthopedic surgery for
      low-energy fracture.
AB  - OBJECTIVE: To develop a cost-effective strategy for improving osteoporosis
      management in patients admitted to an orthopedic surgery department for low
      energy fractures. METHODS: From November 2003 to July 2004, all patients over 50
      years admitted to the orthopedics department of the Caen Teaching Hospital
      (France) for low-energy fractures were identified and evaluated by rheumatology
      department physicians in the same hospital. RESULTS: During the study period, 313
      patients were identified, 257 women (mean age, 79.5+/-10.2 years) and 56 men
      (mean age, 74.6+/-10.8 years), each with one fracture (proximal femur, 58.9%;
      wrist, 13%). Among them, 91 (29%) had a previous history of osteoporotic
      fractures. Mean bone mineral density (BMD) values were lower at the femoral neck
      than at the total hip or lumbar spine (e.g. in women, -2.3+/-0.9 versus -1.8+/
      1.0 and -1.4+/-1.7, respectively). Osteoporosis treatment was given to 88 (28%)
      patients and consisted of calcium and vitamin D supplements, combined with
      alendronate in 32 patients. Complete loss of self-sufficiency occurred in 73
      patients. Thus, 161 patients (88 with osteoporosis treatment and 73 with loss of
      self-sufficiency) received optimal treatment. CONCLUSION: Cooperation between the
      orthopedics and rheumatology departments improved the management of osteoporosis
      in patients with low-energy fractures. However, appropriate investigation and
      treatment of osteoporosis proved difficult in the oldest old and in patients with
      cognitive impairments.

PMID- 16987683
TI  - [Poisons for reproduction in work environment].
AB  - This article describes the lawful bases of the reprotoxic risk management in work
      environment, and sets out the recommendations of the French Societe de Medecine
      du Travail (occupational medicine) for the medical supervision of pregnant wage
      earners exposed to toxic substances as far as foetal development is concerned. We
      start with the description of the lawful bases, clarifying the various types of
      classification of toxic substances for reproduction, the particular regulation
      applying to reprotoxic categories 1 and 2, particularly with regard to the
      labelling of these products, the prohibition of availability to the general
      public, the principles of prevention and the guarantees of remuneration of the
      pregnant women exposed to this risk. Then, we present the recommendations worked
      out by the Societe Francaise de Medecine du Travail, with regard to the medical
      supervision of pregnant wage-earners. They include: evaluation of the risk on the
      work place, evaluation of exposure, be it external or internal, presentation of
      methods of calculation of values guides and of recommendations transmitted to
      occupational doctors, before and during the pregnancy of their patients. To
      conclude, it is important to remain rigorous with this reprotoxic risk, by
      referring to the lawful bases at our disposal and supporting the scientific bases
      following epidemiologic studies. Adequate information must be given to women but
      also men pf procreation age. In spite of a well-defined lawful framework,
      watchfulness is required with the new products put on the market and the new
      scientific data.

PMID- 16987684
TI  - [Levonorgestrel-releasing intrauterine system in the treatment of dysfunctional
      uterine bleeding: A French multicenter study].
AB  - OBJECTIVE: To evaluate the levonorgestrel-releasing intra-uterine system as an
      alternative to surgical treatment in patients presenting with menorrhagia.
      PATIENTS AND METHODS: In the set of a prospective multicenter study, 49 patients
      with menorrhagia resistant to medical treatment and/or referred for hysterectomy
      or endometrial ablation were included. Medical visits were organized 3, 6, 12, 24
      and 36 months after insertion of the levonorgestrel-releasing intra-uterine
      system. Visual score of menstrual bleeding and satisfaction index were noted on
      each visit. Transvaginal ultrasound, pap smear, endometrial biopsy, and clinical
      data were retrieved one month before and 12 months after inclusion for tolerance
      evaluation. RESULTS: Renouncement rate was 90.0% (95% CI = 80.7-96.6%). After a
      twelve months follow-up, 86.1% of patients were satisfied or very satisfied with
      their clinical state. We found a significant increase of hemoglobin rates from
      baseline (14,0 versus 12,9 g/dl; P < 10(-4)). Similar increases were also found
      in serum iron and ferritin. DISCUSSION AND CONCLUSION: This study confirms the
      efficacy of the levonorgestrel-releasing intra-uterine system in the control and
      reduction of menstrual blood loss in patients with dysfunctional uterine
      bleeding. The high rate of surgery cancellation is a proof of the potential role
      of the levonorgestrel-releasing intra-uterine system as an alternative treatment
      in these patients.

PMID- 16987685
TI  - [Rotterdam consensus in adolescent girls: which investigations and how to
      interpret them to make the diagnosis of PCOS? Gynecol Obstet Fertil 2006;34:341
      6].

PMID- 16987686
TI  - [For or against the use of clomiphene citrate for unexplained infertilities
      Gynecol Obstet Fertil 2006;34:60-69 ].

PMID- 16987687
TI  - [Glycol ethers reproductive risks].
AB  - Glycol ethers (GE) are a family of solvents, the use of which has increased
      dramatically since the 60's, in domestic and occupational mainly water-based
      products, such as paintings, inks, varnishes, cleaning agents. There are two
      subgroups: E series and P series. EGME, among the E series, is the reference
      substance. This is a reprotoxic chemical causing infertility and genital
      apparatus atrophy on both sexes, embryofetal toxicity through maternal exposure
      (malformation, growth alterations and functional deficits). European Union has
      classified nine other GE as reprotoxic. P series, with the beta isomers
      exception, has no specific reprotoxicity. Epidemiological studies published from
      the 80's onwards, have confirmed animal data (malformation, oligoazoospermia,
      spontaneous abortion, hypofertility). The effects can be observed even after the
      end of exposure. Risk assessment studies tend to prove that this massive exposure
      during several decades could have had an important impact on reproductive human
      health. Even if this exposure has considerably decreased since the last few
      years, a ban of reprotoxic GE, as required by two official bodies (CSC, CSHPF),
      seems necessary, due to the high risk level. Classification should be completed
      for some GE, not classified now (EGBE). Health assessment of past exposure should
      be carried out. Physicians should look after a possible glycol ethers
      responsibility when facing this kind of reprotoxic effects.

PMID- 16987688
TI  - [Early recurrent spontaneous abortion: How to take care in 2006?].
AB  - More than 1% of the couples whishing children suffer from recurrent miscarriage,
      but investigations and treatment are not consensual. Most patients have several
      risk factors, and a minimum investigation of known factors has to be undertaken:
      karyotyping of the couple, hysteroscopy for searching uterine anatomic anomalies,
      evaluation for thrombophilias (anticardiolipin antibodies, lupus anticoagulant,
      protein C activity, Proteine S activity, factor V Leiden and factor II mutations,
      activated protein C resistance), antinuclear antibodies. Systemic diseases (like
      lupus) and endocrine abnormalities (like thyroid diseases and diabetes mellitus)
      have to be detected by clinical examination and questioning. No endocrine
      investigation is recommended, unless irregular menstruations or sterility.
      Research in recurrent pregnancy loss are conducted in new associated factors,
      such as skewed-X-chromosome inactivation, maternal HLA types, modifications in
      specific immune molecules and cells regulation. Therapeutic proposals are
      preimplantation genetic diagnosis in case of abnormal karyotiping, hysteroscopic
      surgery for septate uterus, aspirin plus heparin in antiphospholipid-positive
      patients, and aspirin plus corticosteroids in systemic lupus. Heparin seems to
      improve obstetrical prognosis for patients with congenital or acquired
      thrombophilias, but there are only few studies carried out on the subject. This
      new therapeutic approach should incite the patients with a negative medical
      appraisal to be referred to specialized consultations in order to include them in
      eventual clinical tests. Finally, empathic listening and psychological support
      are necessary in a pathology with multiple etiological factors.

PMID- 16987689
TI  - Combined ultrasound-laccase assisted bleaching of cotton.
AB  - This study evaluates the potential of using ultrasound to enhance the bleaching
      efficiency of laccase enzyme on cotton fabrics. Ultrasound of low intensity (7W)
      and relatively short reaction time (30 min) seems to act in a synergistic way
      with the enzyme in the oxidation/removal of the natural colouring matter of
      cotton. The increased bleaching effect could be attributed to improved diffusion
      of the enzyme from the liquid phase to the fibres surface and throughout the
      textile structure. On the other hand inactivation of the laccase occurred
      increasing the intensity of the ultrasound. However, at the ultrasound power
      applied in the bleaching experiments the loss of enzyme activity was not
      significant enough to justify the use stabilizer such as polyvinyl alcohol.
      Furthermore, the polyvinyl alcohol appears to be a substrate for the laccase.

PMID- 16987690
TI  - Stability and decolourization ability of Trametes villosa laccase in liquid
      ultrasonic fields.
AB  - We report in this study that the sonication of laccase from Trametes villosa and
      bovine serum albumin promotes the formation of protein aggregates with high
      molecular weight. The formation of aggregates leads to the deactivation of the
      enzyme, fact that was confirmed by the analysis of the enzyme stability (half
      life time) upon ultrasound treatment. This inactivation was mainly caused by the
      radicals formed by the cavitation phenomenon. It was verified that the addition
      of polyvinyl alcohol to laccase had a protecting effect against enzyme
      inactivation. The performance of laccase in the decolourization of indigo carmine
      was studied. It was observed that the best results were attained when the dye
      solution was treated with ultrasound and enzyme stabilized with polyvinyl
      alcohol, where more than 65% of decolourization was achieved. This value is
      remarkably higher than that attained for the enzyme alone, which was only able to
      decolourize 20% of the dye solution within 1h of treatment. These results have
      important implications for the exploitation of sonication in textile industry,
      where the pollution caused by the release of dyes into effluents is one of the
      major concerns.

PMID- 16987691
TI  - Assessment of fine motor control in patients with occupation-related lateral
      epicondylitis.
AB  - Lateral epicondylitis (LE) is a common overuse injury related to a mechanical
      overload of the wrist extensors' origin; however, some patients also complain of
      clumsiness suggesting a possible motor control problem. The purpose of this study
      was to examine for differences in fine motor control ability between subjects
      with LE and matched control subjects. Subtests of the Purdue Pegboard Test (PPT)
      and the Complete Manual Dexterity Test (CMDT) were administered to 28 subjects
      with LE, and 28 age, gender, and hand dominance-matched control subjects. The LE
      group demonstrated a significant decrease in fine motor control ability on both
      measures, compared with the control group on both the PPT, F(1,52)=9.98, P=0.003,
      and the CMDT, F(1,52)=18.11, P=0.001. There appeared to be no effect for the
      length of time since injury. There were significant differences in fine motor
      control ability between individuals with LE and a matched control group for both
      measures used. These results suggest that tests of fine motor control should be
      considered in the assessment of clients with LE. The mechanism related to the
      deficit is unknown and warrants further research.

PMID- 16987692
TI  - Measurement of segmental cervical multifidus contraction by ultrasonography in
      asymptomatic adults.
AB  - The deep muscles that play significant roles in maintaining segmental stability
      have been measured using ultrasonography (US). However, few studies have been
      carried out to determine the reliability and validity of US for measuring the
      cervical multifidus during contraction. The aims of this investigation were to
      evaluate the reliability of the dimensions of the cervical multifidus as measured
      using US and compare the US measurements with those determined with magnetic
      resonance imaging (MRI), the gold standard. Ten asymptomatic adult subjects (age,
      28.5+/-3.5 years) participated in testing-retesting of muscle dimensions at rest
      and during isometric head extension with the cranio-cervical spine maintained in
      a flexed position against individual maximum resistance. Ten asymptomatic adult
      subjects (age, 28.1+/-4.1 years) participated in testing to compare US and MRI
      measurements of the thickness, width, area, and shape ratio of the cervical
      multifidus at the C4, C5, and C6 levels. US measurements of muscle thickness at
      the C4, C5, and C6 levels at rest were 0.67+/-0.14, 0.70+/-0.20 and 0.73+/-0.09
      cm, respectively; the corresponding measurements as determined by MRI were 0.70+/
      0.12, 0.67+/-0.15 and 0.70+/-0.06 cm. The within-subject coefficient of variation
      (CV(w)) for thickness at rest and during contraction was less than 10%,
      indicating acceptable reliability. US measurement of thickness had better
      reliability and validity. The range of limit of agreement for muscle thickness at
      the C4, C5, and C6 levels was -0.20 to 0.20 cm, and the range of R(2) was 0.42
      0.64. The thickness of the cervical multifidus muscle increased significantly
      during contraction (1.13+/-0.20, 1.19+/-0.20 and 1.17+/-0.12 cm for the C4, C5,
      and C6 levels, P<0.05). However, no significant differences were noted among the
      three levels. The results indicate that US can detect changes in segmental
      cervical multifidus during contraction.

PMID- 16987693
TI  - Early detection of oral cancer - Is dielectrophoresis the answer?
AB  - The early detection of oral squamous cell carcinoma by non-invasive methods has
      the potential to hasten diagnosis and thus lessen the morbidity associated with
      tumour therapy. Dielectrophoresis (DEP) can non-invasively determine
      electrophysiological parameters such as conductivity and permittivity of cellular
      cytoplasm and membrane. The present study demonstrates that DEP can be utilised
      to characterise H357 and UP cells and reveals that there are significant
      differences in these parameters between malignant and more normal epithelial cell
      lines. The present results suggest that DEP has potential for the early detection
      of cancerous from non-cancerous cells in a clinical setting.

PMID- 16987694
TI  - Genotoxic evaluation of extracts from Aplysina fulva, a Brazilian marine sponge.
AB  - A range of biologically active secondary metabolites with pharmacological
      application has been reported to occur in marine sponges. The present study was
      undertaken to provide a set of data on the safety of a hydro-alcoholic extract
      (ALE) and an aqueous fraction (AQE) from Aplysina fulva Pallas, 1766
      (Aplysinidae, Verongida, Porifera). Salmonella typhimurium strains TA97, TA98,
      TA100 and TA102, Escherichia coli strains PQ65, OG40, OG100, PQ35 and PQ37 and
      Balb/c 3T3 mouse fibroblasts were used to detect induction of DNA lesions by ALE
      and AQE. Assays used for these analyses were a bacterial (reverse) mutation assay
      (Ames test), the SOS-chromotest and the comet assay. Both extracts presented
      identical infrared 2-oxazolidone spectra. ALE treatment induced a higher
      frequency of type-4 comets, indicative of increasing DNA migration, in the
      alkaline comet assay. ALE also induced a weak genotoxic effect, as expressed by
      the induction factor (IF) values in the test with E. coli strain PQ35 (IF=1.5)
      and by cytotoxic effects in strains PQ35, PQ65 and PQ37. Positive SOS induction
      (IF=1.7) was detected in strain PQ37 treated with diluted AQE. No genotoxic
      effects were observed in strains PQ35, PQ65, OG40 and OG 100 after treatment with
      AQE dilutions. Using the bacterial (reverse) mutation test and survival assays
      with or without S9 mix, after 60min of pre-incubation, we observed for strain
      TA97 treated with ALE a weak mutagenic response (MI=2.2), while cytotoxic effects
      were seen for strains TA98, TA100 and TA102. AQE did not show mutagenic activity
      in any of the strains tested, but a weak cytotoxic effect was noted in strain
      TA102. Our data suggest that both ALE and AQE from A. fulva induce DNA breaks
      leading to cytotoxicity and mutagenicity under the conditions used.

PMID- 16987695
TI  - Microsatellite analysis for determination of the mutagenicity of extremely low
      frequency electromagnetic fields and ionising radiation in vitro.
AB  - Extremely low-frequency electromagnetic fields (ELF-EMF) have been reported to
      induce lesions in DNA and to enhance the mutagenicity of ionising radiation.
      However, the significance of these findings is uncertain because the
      determination of the carcinogenic potential of EMFs has largely been based on
      investigations of large chromosomal aberrations. Using a more sensitive method of
      detecting DNA damage involving microsatellite sequences, we observed that
      exposure of UVW human glioma cells to ELF-EMF alone at a field strength of 1 mT
      (50 Hz) for 12 h gave rise to 0.011 mutations/locus/cell. This was equivalent to
      a 3.75-fold increase in mutation induction compared with unexposed controls.
      Furthermore, ELF-EMF increased the mutagenic capacity of 0.3 and 3 Gy gamma
      irradiation by factors of 2.6 and 2.75, respectively. These results suggest not
      only that ELF-EMF is mutagenic as a single agent but also that it can potentiate
      the mutagenicity of ionising radiation. Treatment with 0.3 Gy induced more than
      10 times more mutations per unit dose than irradiation with 3 Gy, indicating
      hypermutability at low dose.

PMID- 16987696
TI  - The effect of ionizing radiation of 1,4-dihydropyridine derivatives in the solid
      state.
AB  - Electron paramagnetic resonance (EPR) spectroscopy was used to investigate the
      gamma-radiation damage in the crystalline powder form of nine calcium channel
      blockers from the 1,4-dihydropyridine derivatives, which are in clinical use for
      treatment of arteria hypertension and ischemic heart disease. EPR studies have
      been carried out, showing the influence of irradiation and storage parameters on
      the nature and concentration of the free radicals trapped. EPR spectra of
      isardipine and felodipine showed single EPR line. EPR spectra of nifedipine,
      nisoldipine, nitrendipine, nimodipine, nicardipine and nilvadipine reveal a broad
      anisotropic signal of hyperfine interaction. No EPR signal was observed from
      amlodipine.

PMID- 16987697
TI  - An infrared and Raman spectroscopic study of polyanilines co-doped with metal
      ions and H+.
AB  - Polyanilines doped with (HCl+KCl) and (HCl+CoCl2) were prepared by co-doping
      method, respectively. For comparison, polyaniline emeraldine salt (ES) by doping
      with HCl and its emeraldine base (EB) form were also synthesized. The co-doped
      polyanilines, ES and EB samples were all characterized by Fourier transform
      infrared spectroscopy (FTIR) and Raman spectroscopy aiming to understand the
      transformations in the different doping status. The results show that the doping
      degree of K+ ions is considerably higher than that of Co2+ ions under the same co
      doping conditions possibly due to different pseudoprotonation constants of EB
      with K+ ions and Co2+ ions. Moreover, morphology difference of polyaniline co
      doped with alkaline metal ions or transition meal ions may arise from different
      coordination geometry of metal ions. Nevertheless, there are similar chemical
      transformations of quinoid units to benzenoid ones on polyaniline backbones for
      the ES and both co-doped samples. And the polyaniline backbones co-doped with H+
      and metal cations are found to attain weaker charge delocalization than the ES
      which is doped solely with H+.

PMID- 16987698
TI  - Surface-enhanced Raman spectroscopy and density functional theory study on 4,4'
      bipyridine molecule.
AB  - The molecular geometry and vibrational frequencies of 4,4'-bipyridine (BPE) in
      the ground state were calculated using density functional theory (DFT) methods
      (B3LYP) with 6-31++G(d,p) basis set. The optimized geometric bond lengths and
      bond angles are obtained by DFT employing the hybrid of Beckes non-local three
      parameter exchange and correlation functional and Lee-Yang-Parr correlation
      functional. Fourier transform infrared (FT-IR), Fourier transform Raman (FT
      Raman) and near-infrared surface-enhanced Raman scattering (NIR-SERS) spectra of
      BPE on the silver foil substrate have been recorded. All FT-IR, FT-Raman and NIR
      SERS band were assigned on the basis of the B3LYP/6-31++G(d,p) method. The
      vibrational frequencies obtained by DFT(3LYP) are in good agreement with observed
      results. The NIR-SERS of BPE excited by 1064nm laser line is little difference
      with that excited by visible laser line. This phenomenon is result to the
      increase of the contribution of CHEM enhancement effect. Surface selection rules
      derived from the electromagnetic enhancement model were employed to infer the
      orientations of BPE on the silver foil substrate surface. Some vibrational
      frequency which are sensitive to the planar or non-planar structure of BPE, and
      to the dihedral angle were concluded.

PMID- 16987699
TI  - 2-Benzyl-2-methyl-2H-benzimidazole 1,3-dioxide derivatives: Spectroscopic and
      theoretical study.
AB  - The spectroscopic behavior of 2-benzyl-2-methyl-2H-benzimidazole 1,3-dioxide
      derivatives in solution was studied in terms of electronic and nuclear magnetic
      resonance ((1)H and (13)C NMR) techniques. The experimental spectra were compared
      to the theoretical ones, obtained at DFT level, proving that the compounds adopt
      in solution a bird-like conformational distribution. Also, theoretically this
      conformational distribution resulted the most stable in gas phase. Infrared
      spectroscopy was used to study solid state behavior identifying experimentally
      the N-O stretching near to 1380, 1365 and 1225 cm(-1) and the vibrational
      benzimidazole skeleton near to 1610 and 1590 cm(-1). The vibrational spectrum was
      satisfactorily described by DFT calculations funding the N-O stretching as a
      coupled vibration near to 1470, 1350 and 1285 cm(-1). The fragmentation that
      takes place in mass spectrometry was assigned for all of the new derivatives.

PMID- 16987700
TI  - Molecular structures and vibrational frequencies of 2-, 3- and 4-pyridine
      carboxaldehydes by ab initio Hartree-Fock and density functional theory
      calculations.
AB  - The optimised molecular structures, vibrational frequencies and corresponding
      vibrational assignments of the cis and trans conformers of 2-, 3- and 4-pyridine
      carboxaldehydes have been calculated using ab initio Hartree-Fock (HF) and
      density functional theory (B3LYP) methods with 6-311++G(d, p) basis set. The
      calculations were adapted to the C(S) symmetries of all the molecules. The mean
      vibrational deviations between the vibrational frequency values of the two
      conformers of all the compounds have been seen to increase while the relative
      energies increase and it was concluded the more different the molecular structure
      of the two conformers is the higher the relative energy is between them, and thus
      a bigger mean vibrational deviation.

PMID- 16987701
TI  - Spectroscopic properties of Er(3+)/Yb(3+) co-doped Bi(2)O(3)-B(2)O(3)-GeO(2)
      glasses.
AB  - Er(3+)/Yb(3+) co-doped 60Bi(2)O(3)-(40 - x)B(2)O(3)-xGeO(2) (BBG; x=0, 5, 10, 15
      mol%) glasses that are suitable for fiber lasers, amplifiers have been fabricated
      and characterized. The absorption spectra, emission spectra, and lifetime of the
      (4)I(13/2) level and quantum efficiency of Er(3+):(4)I(13/2) --> (4)I(15/2)
      transition were measured and calculated. With the substitution of GeO(2) for
      B(2)O(3), both Delta lambda(eff) and sigma(e) decrease from 75 to 71 nm and 9.88
      to 8.12 x 10(-21) cm(2), respectively. The measured lifetime of the (4)I(13/2)
      level and quantum efficiency of Er(3+):(4)I(13/2) --> (4)I(15/2) transition
      increase from 1.18 to 1.5 ms and 36.2% to 43.2%, respectively. The emission
      spectra of Er(3+):(4)I(13/2) --> (4)I(15/2) transition was also analyzed using a
      peak-fit routine, and an equivalent four-level system was proposed to estimate
      the stark splitting for the (4)I(15/2) and (4)I(13/2) levels of Er(3+) in the BBG
      glasses. The results indicate that the (4)I(13/2) --> (4)I(15/2) emission of
      Er(3+) can be exhibit a considerable broadening due to a significant enhance the
      peak A, and D emission.

PMID- 16987702
TI  - Catalytic-kinetic determination of trace amount of formaldehyde by the
      spectrophotometric method with a bromate-Janus green system.
AB  - A new simple and rapid catalytic kinetic method for the determination of trace
      amount of formaldehyde is described. The method is based on the catalytic effect
      of formaldehyde on the oxidation of Janus green by bromate in the present of
      sulfuric acid. The reaction monitored spectrophotometrically by measuring the
      decrease in absorbance of the reaction mixture at 618 nm. The fixed-time method
      was used for the first 150 s. For initiation of the reaction, under the optimum
      conditions, in the concentration range of 0.003-2.5 microg ml(-1) formaldehyde
      can be determined with a limit of detection 0.0015 microg ml(-1). The relative
      standard deviation of five replicate measurements is 2.3% for 1.0 microg ml(-1)
      of formaldehyde. The method was used for the determination of formaldehyde in
      real samples with satisfactory results.

PMID- 16987703
TI  - Synthesis and novel fluorescence phenomenon of terbium complex with a new Schiff
      base ligand derived from condensation of triaminotriethylamine and 3
      indolemethanal.
AB  - A new Schiff base ligand with tripodal structure, N,N',N''-tri-(3-indolemethanal)
      triaminotriethylamine (L), and its complex with terbium was synthesized. The
      complex was characterized by element analysis, IR spectra, mass spectra, thermal
      analysis and molar conductivity. The terbium ion was found to coordinate to the
      Schiff base nitrogen atoms and the bridgehead nitrogen atom. The fluorescence
      properties of the complex in aqueous solutions were studied. Under the excitation
      of UV light, the complex exhibits characteristic fluorescence of terbium ion.
      H(+) concentration could strongly enhance the luminescence of terbium complex
      with L in aqueous solutions. This phenomenon will make the new complex favorable
      to be used in the fluorescence switches and sensors. The mechanism of the
      fluorescence enhancement by protonation of the indole nitrogen atoms is due to
      the suppressed photoinduced electron transfer (PIET) fluorescence quenching when
      adding acid.

PMID- 16987704
TI  - Influence of Cu(II) on the interaction between sulfite and horseradish peroxidase
      in vitro.
AB  - This paper discussed the quantitative influence of Cu(II) on the interaction
      between horseradish peroxidase (HRP) and sulfite (SO3(2-)), which is a derivate
      of sulfite dioxide in human bodies, by using fluorescence spectrum and
      ultraviolet (UV) absorption spectrometry in vitro. The results show that under
      the conditions of physiological pH and room-temperature, Cu(II) can bind strongly
      with both the protein part and the ferroporphyrin part in HRP at a low
      concentration (10(-4) mol L(-1)), and the combination constants are 2.047 x 10(3)
      and 7.66 x 10(2) L mol(-1), respectively. Under the same conditions, SO3(2-) at
      low concentrations (<0.15 mol L(-1)) has little quenching for the fluorescence of
      HRP at 330 nm, and the combination constant is 0.108 L mol(-1). While the
      fluorescence intensity at 440 nm enhance gradually with the increased
      concentration of SO3(2-) (<0.1 mol L(-1)), and the combination constant is 8.219
      L mol(-1). These indicate that SO3(2-) at low concentration has little reaction
      with the enzyme protein part in HRP but obvious reaction with the ferroporphyrin
      part in HRP. After SO3(2-) at low concentrations is added into the HRP-Cu(II)
      binary system, the reaction constants between SO3(2-) and the enzyme protein part
      in HRP increase rapidly. Compared with the absence of Cu(II), the combination
      constant of SO3(2-) with the enzyme protein part in HRP increases nearly 70 times
      with a certain Cu(II) concentration (5.0 x 10(-4) mol L(-1)) in the system.
      However, the presence of Cu(II) in the system has little effect on the reaction
      constants between SO3(2-) and the ferroporphyrin part in HRP.

PMID- 16987705
TI  - Changes in motor axon recruitment in the median nerve in mild carpal tunnel
      syndrome.
AB  - OBJECTIVE: To determine whether patients with mild carpal tunnel syndrome (CTS)
      and conventional electrodiagnostic evidence of selective involvement of sensory
      conduction show changes in motor axon recruitment in the median nerve. METHODS:
      Wrist-to-abductor pollicis brevis (APB) motor axon conduction was studied by
      analysing the relationship between the intensity of electrical stimulation and
      the size of motor response (input-output curve) in 30 CTS patients with
      conventional electrodiagnostic evidence of selective involvement of sensory
      conduction. Parameters (threshold, slope and plateau) of input-output curves were
      compared with those obtained in 30 controls. RESULTS: The slope of the input
      output curve of CTS patients was less steep than that of controls. For stimulus
      intensity above M-wave threshold (MTh), fewer motor axons were recruited in
      patients than controls. CONCLUSIONS: Motor fibres are affected in CTS when
      conventional electrodiagnostic tests show normal motor conduction. Altered
      recruitment of motor axons could mainly be due to impairment of energy-dependent
      processes which affect temporal dispersion of the compound volley or axonal
      conduction block. SIGNIFICANCE: In mild CTS, motor fibres are more often affected
      than was originally thought. The sensitivity of wrist-to-APB motor conduction
      studies may be increased by using submaximal stimulus intensities.

PMID- 16987706
TI  - GLP-1 and type 2 diabetes: physiology and new clinical advances.
AB  - The first antidiabetic treatment (exenatide; Byetta) based on the incretin
      hormone glucagon-like peptide-1 (GLP-1) was approved in 2005 as an adjunctive
      therapy in diabetic patients in whom sulfonylurea, metformin or both had failed.
      Many GLP-1 mimetics or dipeptidyl peptidase IV inhibitors are currently in
      clinical development for the treatment of type 2 diabetes and show promising
      results in the improvement of glucose homeostasis. Furthermore, the ability of
      GLP-1 to enhance pancreatic beta-cell mass could delay progression of the
      disease. However, only several years of treatment in humans will confirm the long
      term efficacy of GLP-1 mimetics and enhancers on glycemic control. To take
      advantage of the multifaceted actions of GLP-1, a better understanding of the
      physiological roles of GLP-1 is required.

PMID- 16987707
TI  - Analysis of enzymopathies in the human red blood cells by constraint-based
      stoichiometric modeling approaches.
AB  - The human red blood cell (RBC) metabolism is investigated by calculating steady
      state fluxes using constraint-based stoichiometric modeling approaches. For the
      normal RBC metabolism, flux balance analysis (FBA) is performed via optimization
      of various alternative objective functions, and the maximization of production of
      ATP and NADPH is found to be the primary objective of the RBC metabolism. FBA and
      two novel approaches, minimization of metabolic adjustment (MOMA) and regulatory
      on-off minimization (ROOM), which can describe the behavior of the metabolic
      networks in case of enzymopathies, are applied to observe the relative changes in
      the flux distribution of the deficient network. The deficiencies in several
      enzymes in RBC metabolism are investigated and the flux distributions are
      compared with the non-deficient FBA distribution to elucidate the metabolic
      changes in response to enzymopathies. It is found that the metabolism is mostly
      affected by the glucose-6-phosphate dehydrogenase (G6PDH) and phosphoglycerate
      kinase (PGK) enzymopathies, whereas the effects of the deficiency in DPGM on the
      metabolism are negligible. These stoichiometric modeling results are found to be
      in accordance with the experimental findings in the literature related to
      metabolic behavior of the human red blood cells, showing that human RBC
      metabolism can be modeled stoichiometrically.

PMID- 16987708
TI  - Identification of critical genes in microarray experiments by a Neuro-Fuzzy
      approach.
AB  - Gene expression profiling by microarray technology is usually difficult to
      interpret into a simpler pattern. One approach to resolve the complexity of gene
      expression profiles is the application of artificial neural networks (ANNs). A
      potential difficulty in this strategy, however, is that the non-linear nature of
      ANN makes it essentially a 'black-box' computation process. Addition of a fuzzy
      logic approach is useful because it can complement ANN by explicitly specifying
      membership function during computation. We employed a hybrid approach of neural
      network and fuzzy logic to further analyze a published microarray study of gene
      responses to eight bacteria in human macrophages. The original analysis by
      hierarchical clustering found common gene responses to all bacteria but did not
      address individual responses. Our method allowed exploration of the gene response
      of the host to individual bacterium. We implemented a two-layer, feed-forward
      neural network containing the principle of 'competitive learning' (i.e. 'winner
      take-all'). The weights of the trained neural network were fed into a fuzzy logic
      inference system. A new measurement, called the impact rating (IR) was also
      introduced to explore the degree of importance of each gene. To assess the
      reliability of the IR value, a bootstrap re-sampling method was applied to the
      dataset and a confidence level for each IR was obtained. Our approach has
      successfully uncovered the unique features of host response to individual
      bacterium. Further, application of gene ontology (GO) annotation to the genes of
      high IR values in each response has suggested new biological pathways for
      individual host-pathogen interactions.

PMID- 16987709
TI  - Which complement assays and typings are necessary for the diagnosis of complement
      deficiency in patients with lupus erythematosus? A study of 25 patients.
AB  - INTRODUCTION: Deficiencies in components of the classical pathway of complement
      activation are strong risk factors for lupus erythematosus (LE).Yet, it has not
      been addressed whether the conventional measurements of the serum hemolytic CH50
      activity and antigenic concentrations of C3 and C4 are sufficient to asses a
      deficiency in C4A, C4B or C2 components, the most common deficiencies associated
      with LE. PATIENTS AND METHODS: In a retrospective series, we performed complement
      analyses in 35 patients with LE who were systematically screened for a complement
      deficiency. The majority of patients had cutaneous LE with mild systemic
      involvement and no complement consumption. Of 25 patients (72%) with complement
      deficiency we found 13 with a partial C4A deficiency, 2 with a complete C4A
      deficiency, 6 with a partial C4B deficiency, 2 with a complete C4B deficiency and
      2 with a combined partial C2 and C4A deficiency. RESULTS: The total complement
      activity (CH50) was decreased in only one out of two patients with complete C4B
      deficiency. CH50 level was found to be low-normal (35-38 U/ml(-1)) in one patient
      with partial C4B deficiency, one patient with complete C4B deficiency and both
      patients with combined partial C4A and C2 deficiency. Total C4 levels were normal
      in 9 out of 13 the patients with a partial C4A deficiency and in 2 out of 6
      patients with a complete C4B deficiency. The antigenic concentration of C3 was
      low in only 1 patients with a complete C4B deficiency and within the normal range
      in all the others patients. Overall, 50% of the patients had normal or elevated
      C3, C4, and CH50 levels. DISCUSSION: This study emphasizes that the usual
      measurements of CH50, C3 and C4 levels are not adequate to detect a C4 and/or C2
      deficiency in patients with LE. In epidemiologic or investigative studies
      addressing the prevalence of complement deficiency, more elaborated diagnostic
      tests, such as C4 protein allotyping, C2 level measurement and genetic screening
      for type I C2 deficiency should also be performed.

PMID- 16987710
TI  - Normalized CD8+ but not CD4+ lymphocyte IL-2 expression is associated with early
      treatment with highly active antiretroviral therapy.
AB  - CD4+ and CD8+ lymphocyte cytokine production in patients with HIV/AIDS and
      Controls, in response to stimulation with phorbol-12-myristate-13-acetate (PMA)
      and ionomycin was assessed using single cell flow cytometric methods. Sixty-eight
      patients with HIV were divided into those on no antiretroviral therapy and those
      on highly active antiretroviral therapy (HAART). Patients on HAART were analyzed
      further on the basis of gender, ethnicity, viral load (> or </=50 copies/ml), CD4
      count change from nadir (>100 or <100 cells/mm(3)) and CD4 count (>200 or <200
      cells/mm(3)). Interferon gamma (IFNgamma) expression by CD4+ and CD8+ lymphocytes
      was elevated in HIV-infected groups as compared to Controls. This elevation was
      statistically significant for patients on HAART but not for those not on HAART.
      The most significant difference was seen when the CD4+ count reached >200
      cells/mm(3) (p=0.018 for CD4+ IFNgamma production and p=0.004 for CD8+ IFNgamma
      production). CD4+ interleukin-2 (IL-2) expression was significantly lower in HIV
      patients as compared to Controls but did not significantly improve however good
      the response to HAART. IL-2 expression by CD8+ lymphocytes was also lower in HIV
      patients as compared to Controls. IL-2 expression by CD8+ lymphocytes
      significantly improved in all patients on HAART as compared to HIV patients on no
      HAART. IL-2 expression was not significantly different from that of the Controls
      when the HIV viral load was less than 50 copies/ml. These results demonstrate
      improvements in both CD4+ and CD8+ responsiveness with HAART. IFNgamma production
      was elevated in response to HAART and was maximal only with significant CD4 count
      recovery. In contrast, normalization of IL-2 production by CD8+ lymphocytes was
      seen early in patients receiving HAART even when there was only a small increase
      in CD4+ lymphocyte numbers.

PMID- 16987711
TI  - Enhanced efficacy of an AAV vector encoding chimeric, highly secreted acid alpha
      glucosidase in glycogen storage disease type II.
AB  - Glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) is an
      inherited muscular dystrophy caused by deficiency in the activity of the
      lysosomal enzyme acid alpha-glucosidase (GAA). We hypothesized that chimeric GAA
      containing an alternative signal peptide could increase the secretion of GAA from
      transduced cells and enhance the receptor-mediated uptake of GAA in striated
      muscle. The relative secretion of chimeric GAA from transfected 293 cells
      increased up to 26-fold. Receptor-mediated uptake of secreted, chimeric GAA
      corrected cultured GSD-II patient cells. High-level hGAA was sustained in the
      plasma of GSD-II mice for 24 weeks following administration of an AAV2/8 vector
      encoding chimeric GAA; furthermore, GAA activity was increased and glycogen
      content was significantly reduced in striated muscle and in the brain.
      Administration of only 1 x 10(10) vector particles increased GAA activity in the
      heart and diaphragm for >18 weeks, whereas 3 x 10(10) vector particles increased
      GAA activity and reduced glycogen content in the heart, diaphragm, and
      quadriceps. Furthermore, an AAV2/2 vector encoding chimeric GAA produced secreted
      hGAA for >12 weeks in the majority of treated GSD-II mice. Thus, chimeric, highly
      secreted GAA enhanced the efficacy of AAV vector-mediated gene therapy in GSD-II
      mice.

PMID- 16987712
TI  - Total power and high frequency components of heart rate variability and risk
      factors for atherosclerosis.
AB  - INTRODUCTION: Low heart rate variability, HRV, is associated with diabetic
      neuropathy and with ischemic heart disease, IHD. The time context points to
      diabetes preceding changes in HRV, while changes in HRV precede the development
      of atherosclerosis and IHD. The purpose of the study was to analyse the
      association between the physiological risk factors of IHD and HRV in a
      prospective design. METHODS: In 1998 and 2002, data was gathered in a study
      concerning the risk factors for atherosclerosis. From among the participants it
      was possible to include 50 women and 24 men in a sub-study concerning HRV. Heart
      rate variability was measured partly during a clinical examination with exposure
      to a simple stress test, and partly during the first 4 h of sleep. The clinical
      examination, which lasted 45 min, resulted in 9, 5-minute HRV measurements, while
      the sleep period was divided into 2 periods of 2 h each, for which average HRV
      measurements were calculated. The associations between HRV and risk factors for
      IHD were analysed using the GLM, repeated measures method. As the dependent
      variables in the GLM analyses 11 levels (9 while awake and 2 while sleeping) of
      total power and high frequency variability, respectively, were used. The included
      risk factors were; body mass index, waist-hip ratio, systolic blood pressure,
      fibrinogen, cholesterol, HDL-cholesterol, HbA1c, testosterone, DHEAs, cortisol
      and catecholamines. Catecholamines were measured in urine and only in 1998.
      Cortisol was measured in both urine and saliva in 1998, but only in saliva in
      2002. The results were adjusted according to the starting time of the
      measurements. RESULTS: Among the women, waist-hip ratio and HbA1c were
      significantly and negatively associated with both TP and HF. Stress hormones were
      not associated with HRV. Among the men, waist-hip ratio, HbA1c, and fibrinogen in
      2002, and cortisol and noradrenaline in 1998 were significantly and negatively
      associated with TP and HF. CONCLUSION: The study showed gender differences in the
      observed associations. In both gender, waist ratio and HbA1c were negatively
      associated with TP and HF. Furthermore, in the men, but not in the women, stress
      hormones in 1998, i.e. cortisol and noradrenaline, was negatively associated with
      TP and HF. The presented data give rise to discussion of the pathophysiology
      behind heart rate variability and ischemic heart disease, which may be different
      between women and men.

PMID- 16987713
TI  - Effect of aminoguanidine treatment on diabetes-induced changes in the myenteric
      plexus of rat ileum.
AB  - The aim of this study was to investigate the ability of aminoguanidine (AG) to
      prevent diabetes-induced changes in nitric oxide synthase- (nNOS), vasoactive
      intestinal polypeptide- (VIP) and noradrenaline- (NA) containing nerves of the
      rat ileum using immunohistochemical and biochemical techniques. Diabetes was
      induced in adult male Wistar rats by a single intraperitoneal injection of
      streptozotocin (65 mg/kg). AG was administered in the drinking water to control
      (1.8 g/l) and diabetic (0.9 g/l) rats over a period of 8 weeks. Diabetes caused a
      significant increase in the thickness of nNOS-containing nerve fibres (p<0.001)
      in the circular muscle, in nNOS activity (p<0.05) and in the size distribution of
      nNOS-containing myenteric neurons (p<0.001). The thickness of VIP-containing
      nerve fibres was significantly greater (p<0.01) and there was a significant
      increase in varicosity size (p<0.01) and proportion of VIP-positive myenteric
      neurons (p<0.01) in diabetes. NA levels were significantly reduced (p<0.01) and
      the size of varicosities containing tyrosine hydroxylase (TH) was significantly
      increased (p<0.001) in diabetes. AG treatment completely or partially prevented
      the diabetes-induced increase in nNOS activity, in VIP-containing varicosity
      size, and in fibre width of both VIP- and nNOS-containing fibres in the circular
      muscle but had no effect on the diabetes-induced increase in nNOS-containing
      neuronal size or proportion of VIP-containing myenteric neurons. In contrast to
      VIP, AG treatment had no effect on the increase in TH-containing varicosity size
      in diabetes and also failed to prevent the decrease in NA levels induced by
      diabetes. These results indicate that AG treatment for neuropathy is not equally
      effective for all autonomic nerves supplying the ileum and that diabetes-induced
      changes in NA-containing nerves are particularly difficult to treat.

PMID- 16987714
TI  - Interaction of tin(II) and arsenic(III) with DNA at the nanostructure film
      modified electrodes.
AB  - Biosensors based on DNA and DNA-carbon nanotubes film immobilized at the surface
      of a screen-printed carbon electrode were used for simple in vitro tests of
      chemical toxicity. The damage to DNA caused by tin(II) and arsenic(III) compounds
      as components of specific reaction media was evaluated by means of an
      electrochemical DNA marker, [Co(phen)3](3+), as the portion of original dsDNA
      which survives an incubation of the biosensor in the cleavage medium. The results
      were confirmed by the electrically heated electrode and by the measurement of the
      DNA guanine moiety signal.

PMID- 16987715
TI  - Rad52 and Rad59 exhibit both overlapping and distinct functions.
AB  - Homologous recombination is an important pathway for the repair of DNA double
      strand breaks (DSBs). In the yeast Saccharomyces cerevisiae, Rad52 is a central
      recombination protein, whereas its paralogue, Rad59, plays a more subtle role in
      homologous recombination. Both proteins can mediate annealing of complementary
      single-stranded DNA in vitro, but only Rad52 interacts with replication protein A
      and the Rad51 recombinase. We have studied the functional overlap between Rad52
      and Rad59 in living cells using chimeras of the two proteins and site-directed
      mutagenesis. We find that Rad52 and Rad59 have both overlapping as well as
      separate functions in DSB repair. Importantly, the N-terminus of Rad52 possesses
      functions not supplied by Rad59, which may account for its central role in
      homologous recombination.

PMID- 16987716
TI  - Comparative proteomics of rat liver and Morris hepatoma 7777 plasma membranes.
AB  - Plasma membranes from normal rat liver and hepatocellular carcinoma Morris
      hepatoma 7777 were selectively solubilized by use of different reagents. After
      selective solubilization, proteins were identified by nano-HPLC-electrospray
      ionization tandem mass spectrometry (LC-ESI MS/MS). Using simple software, the
      patterns of proteins identified in membrane solubilizates from liver and hepatoma
      were compared. Proteins identified in Morris hepatoma 7777 and not in the
      corresponding membrane solubilizate from liver, mostly members of the annexin and
      heat shock protein families, are discussed as potential candidate markers for
      hepatocellular carcinomas.

PMID- 16987717
TI  - High-sensitivity profiling of glycoproteins from human blood serum through
      multiple-lectin affinity chromatography and liquid chromatography/tandem mass
      spectrometry.
AB  - We report here the use of high-performance lectin affinity enrichment of
      glycoproteins at microscale levels using a series of silica-bound lectins. The
      potential of this approach is being demonstrated for the glycoprotein enrichment
      from microliter volumes of human blood serum. Individual injections of sample to
      the affinity microcolumns packed with four lectin materials with different glycan
      specificities (Con A, SNA-I, UEA-I, PHA-L), followed by off-line reversed-phase
      pre-fractionation and nano-LC/MS/MS, permitted identification of 108 proteins in
      the lectin-bound fractions spanning a concentration dynamic range of 7-10 orders
      of magnitude. In contrast, multi-lectin microcolumn affinity chromatography, an
      alternative enrichment approach allowed identification of only 67 proteins. An
      attractive feature of high-performance lectin affinity chromatography at
      microscale levels is the substantial reduction of sample losses that are commonly
      experienced with extensive sample preparation needed for larger sample volumes.

PMID- 16987718
TI  - Economic transition and household food consumption: a study of Bulgaria from 1985
      to 2002.
AB  - Major economic transitions typically entail changes in the availability of and
      purchasing power for different types of foods leading to long-term changes in the
      composition of the diet. Bulgaria, a former Eastern Bloc country, underwent a
      difficult and protracted transition from a centralized to market economy with
      acute economic crises and a much slower recovery of income levels than in Poland,
      the Czech Republic, and Hungary. Using annual data from the Bulgarian National
      Household Survey, we study changes in the reported consumption of major foods
      (excluding alcoholic drinks) and their constituent macronutrients from 1985 to
      2002, examining also the differences in dietary patterns between the period prior
      to and following the transition. The consumption of most major food items
      decreased, resulting in a fall in per capita energy consumption of 429 kcal/day
      (1.80 MJ/d), following the economic transition of 1991. As expected, the
      consumption of foods that were more expensive per unit of energy decreased
      greater than cheaper foods, -34% for animal products and -19% for visible fats,
      but only -10% for carbohydrates. These changes are related to the changes in
      income and market prices as well as the general negative trend in economic growth
      and hyperinflation in the mid-1990s. Thus, Bulgaria experienced a decrease in
      food consumption without significant changes in the dietary pattern following the
      economic transition of 1991. The fact that part of this decline may be attributed
      to continued economic challenges suggests that future transitions in the diet may
      be expected as economic development proceeds.

PMID- 16987719
TI  - Structural characterization of an unusually stable cyclic peptide, kalata B2 from
      Oldenlandia affinis.
AB  - Kalata peptides are isolated from an African medicinal plant, Oldenlandia
      affinis, an aqueous decoction of which can be ingested to accelerate uterine
      contraction during childbirth. The closely packed disulfide core of kalata
      peptides confers unusual stability against thermal, chemical, and enzymatic
      degradation. The molecular arrangement may hamper NMR-assisted disulfide
      connectivity assignment. We have combined NMR with high-resolution mass
      spectrometry (MS) and MS/MS of native and chemically derivatized kalata B2 to
      determine its amino acid sequence and disulfide connectivity. Infrared
      multiphoton dissociation establishes the disulfide bond linkages in kalata B2 as
      I-IV, II-V and III-VI.

PMID- 16987720
TI  - In vivo association to human colon of Lactobacillus paracasei B21060: map from
      biopsies.
AB  - BACKGROUND: Adhesion to the intestinal mucosa is one of the main suitable
      properties for probiotic bacteria. Several in vitro studies have been published,
      but a very few data are available about the in vivo adhesion to intestinal
      surfaces of probiotics. Moreover, there are no data regarding the distribution of
      a probiotic strain along the entire intestine. AIM: The present study aimed to
      preliminary evaluate the intestinal recovery of a new synbiotic formulation
      containing Lactobacillus paracasei B21060. METHODS: Seven volunteers participated
      in the study. Subjects assumed three times a day for 15 days a sachet with a
      synbiotic preparation containing 5 x 10(9)CFUs of Lactobacillus paracasei strain
      B21060. Samples were recovered from the faeces and from the cecum, transverse,
      descending and sigmoid colon. RESULTS: Identification at strain level showed that
      following administration, strain B21060 could be recovered from all sampled sites
      (except in one subject), representing 66.6% of the total vancomycin insensitive
      CFUs isolated from faecal samples, and 74.7% isolated from colonic samples.
      CONCLUSIONS: Our results demonstrate that Lactobacillus paracasei B21060
      probiotic strain is able to temporarily associate throughout the different sites
      of the entire intestinal tract.

PMID- 16987721
TI  - Neglected consequences of a misunderstood disease.

PMID- 16987722
TI  - Excess mortality in epilepsy in developing countries.

PMID- 16987723
TI  - Progression of atrophy in Alzheimer's disease.

PMID- 16987724
TI  - Ultra-early doppler sonography for stroke.

PMID- 16987725
TI  - The use of MRI in the diagnosis of multiple sclerosis.

PMID- 16987726
TI  - Statins after transient ischaemic attack and ischaemic stroke.

PMID- 16987727
TI  - Brain growth in preterm babies.

PMID- 16987728
TI  - Premature mortality in people with epilepsy in rural China: a prospective study.
AB  - BACKGROUND: In China, few studies have described annual mortality associated with
      epilepsy in a general population and these have provided a range of 3.0-7.9
      deaths per 100,000 people. We calculated the case fatality rate (CFR),
      proportional mortality rate (PMR), and standardised mortality ratio (SMR) to
      assess mortality in people with epilepsy in rural China. METHODS: The target
      population was people with epilepsy who participated in an assessment of epilepsy
      management at primary health level in rural China. Neurologists confirmed the
      diagnosis using strict criteria in all participants who were then treated with
      phenobarbital. Demographic data and putative cause of death were recorded for
      each person whose death was reported. PMRs for each cause of death and SMRs were
      estimated on the basis of the 2004 Chinese population. FINDINGS: Case fatality
      rate was 1.4% (35 deaths) among 2455 people with epilepsy. The age-adjusted PMRs
      for injury, stroke, neoplasm, myocardial infarction, and pneumonia were 30%, 30%,
      15%, 6%, and 5%, respectively. The SMR was 3.9 (95% CI 3.8-3.9). Patients aged 15
      29 years had higher mortality ratios than did those in other age-groups, with
      SMRs exceeding 23. INTERPRETATION: Risk for premature death is three to four
      times higher in people with epilepsy than in the general Chinese population.
      Furthermore, the risk in young people with epilepsy in China is much higher than
      previously reported. Injury, stroke, myocardial infarction, and pneumonia are
      among the leading putative causes of death in patients with epilepsy in rural
      China.

PMID- 16987729
TI  - Tracking atrophy progression in familial Alzheimer's disease: a serial MRI study.
AB  - BACKGROUND: Serial MRI scanning of autosomal dominant mutation carriers for
      Alzheimer's disease provides an opportunity to track changes that could predate
      symptoms or clinical diagnosis of the disease. We used hierarchical modelling to
      assess how hippocampal and whole-brain volumes change as familial Alzheimer's
      disease progresses from the presymptomatic stage through to diagnosis. METHODS:
      Nine mutation carriers had serial clinical assessments and volumetric MRI scans
      (41 scans: range 3-8 per patient) at different clinical stages (presymptomatic,
      mild cognitive impairment, or clinical Alzheimer's disease). 25 healthy controls
      had serial scanning (54 scans: range 2-4 per patient) for comparison. We measured
      whole brain and total hippocampal volumes using semi-automated techniques, and
      adjusted for total intracranial volume. Hierarchical models were developed to
      estimate differences in volume and atrophy rate between mutation carriers and
      controls in relation to when the disease was clinically diagnosed. FINDINGS:
      Mutation carriers had significantly increased hippocampal and whole-brain atrophy
      rates compared with controls and these differences increased with time.
      Differences in hippocampal and whole-brain atrophy rates between controls and
      mutation carriers were evident 5.5 and 3.5 years, respectively, before diagnosis
      of Alzheimer's disease. At a cross-sectional level, differences in mean
      hippocampal volume between mutation carriers and controls became significant 3
      years before clinical diagnosis, whereas differences in mean brain volumes became
      significant only 1 year before diagnosis. INTERPRETATION: Structural changes can
      be seen on MRI scans that predate the clinical onset of familial Alzheimer's
      disease. Longitudinal measures of atrophy rates can identify differences between
      mutation carriers and controls 2-3 years earlier than cross-sectional volumetric
      measures.

PMID- 16987730
TI  - Prognostic relevance of ultra-early doppler sonography in acute ischaemic stroke:
      a prospective multicentre study.
AB  - BACKGROUND: Ischaemic stroke can result from a temporary or permanent occlusion
      of intracranial arteries. In the hyperacute stage of the disease cerebrovascular
      ultrasound can be used to determine the vascular pathology, but the significance
      of very early findings on ultrasound is unclear. The present study aimed to
      assess the prognostic value of doppler ultrasonography within the first hours
      after stroke for functional outcome. METHODS: In a prospective multicentre
      design, patients with clinical signs of ischaemic anterior-circulation stroke
      were examined by doppler ultrasonography of the intracranial and extracranial
      arteries. Patients were separated into three groups according to the findings:
      normal middle-cerebral artery (MCA); branch occlusions; or a main-stem occlusion.
      The primary endpoint was functional outcome at 3 months. Logistic regression was
      used to test the association between the ultrasound diagnosis and functional
      outcome. RESULTS: 361 patients were identified with moderate to severe clinical
      deficits (National Institutes of Health Stroke Scale score 5-25). Of these, 121
      (34%) had a normal MCA, 176 (48%) had branch occlusions, 7 (2%) had severe MCA
      stenosis, and 57 (16%) had a main-stem occlusion. 50 of the 57 (88%) patients
      with main-stem occlusion were dead or dependent 3 months after stroke. An
      occlusion of the main stem of the MCA within 6 h after stroke was an independent
      predictor for poor outcome (p=0.0006). 50% of patients with ultrasonographic
      diagnosis of branch occlusions and 63% with normal MCA had a good outcome.
      Combination of CT scan without early signs of infarction and a normal MCA
      resulted in a predictive value of 71% for a good functional outcome.
      INTERPRETATION: Cerebrovascular ultrasonography provides additional functional
      prognostic information in the hyperacute stage of ischaemic stroke. The technique
      is practical in a well-resourced unit, can be used to identify patients with high
      risk for poor functional outcome, and thus would be an appropriate investigation
      for future trials.

PMID- 16987731
TI  - MRI and the diagnosis of multiple sclerosis: expanding the concept of "no better
      explanation".
AB  - Although the diagnosis of multiple sclerosis relies on the demonstration of
      disease dissemination in space and time, the exclusion of other neurological
      disorders is also essential. The limited specificity of abnormalities disclosed
      by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients
      affected by other disorders. The available criteria for diagnosis of multiple
      sclerosis have not taken advantage of the potential of MRI to detect features
      "not suggestive" of multiple sclerosis. Recognition of such features in the work
      up of patients suspected of having multiple sclerosis may reduce the likelihood
      of a false positive diagnosis of the disorder in some, while suggesting the
      correct alternative diagnosis in other patients. On the basis of this, a workshop
      of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was
      held to define a series of MRI red flags in the setting of clinically suspected
      multiple sclerosis that is derived from evidence-based findings and educated
      guesses. The presence of such red flags should alert clinicians to reconsider the
      differential diagnosis more extensively. In this review we will report on the
      conclusions of this international consensus, which should represent a first step
      beyond the concept of "no better explanation", and inform future diagnostic
      criteria for multiple sclerosis.

PMID- 16987732
TI  - Optical coherence tomography in multiple sclerosis.
AB  - We do not have currently satisfactory clinical and anatomical correlates to gauge
      disability in multiple sclerosis. Structural biomarkers (such as MRI) are
      hindered because they cannot precisely segregate demyelination from axonal
      elements of tissue injury within the CNS. Axonal degeneration in multiple
      sclerosis is related to irreversible disability, which suggests that the
      confirmation of neuroprotective strategies needs highly quantifiable measures of
      axon loss that can be correlated with reliable measures of physiological
      function. The coupling of quantifiable measures of visual function with ocular
      imaging techniques, such as optical coherence tomography, enables us to begin to
      understand how structural changes in the visual system influence function in
      patients with multiple sclerosis. In this review, we consider the usefulness of
      optical imaging of the retina as a biomarker for neurodegeneration in multiple
      sclerosis.

PMID- 16987733
TI  - Treatment of dystonia.
AB  - Dystonia, defined as a neurological syndrome characterised by involuntary,
      patterned, sustained, or repetitive muscle contractions of opposing muscles,
      causing twisting movements and abnormal postures, is one of the most disabling
      movement disorders. Although gene mutations and other causes are increasingly
      recognised, most patients have primary dystonia without a specific cause.
      Although pathogenesis-targeted treatment is still elusive, the currently
      available symptomatic treatment strategies are quite effective for some types of
      dystonia in relieving involuntary movements, correcting abnormal posture,
      preventing contractures, reducing pain, and improving function and quality of
      life. A small portion of patients have a known cause and respond to specific
      treatments, such as levodopa in dopa-responsive dystonia or drugs that prevent
      copper accumulation in Wilson's disease. Therapeutic options must be tailored to
      the needs of individual patients and include chemodenervation with botulinum
      toxin injections for patients with focal or segmental dystonia, and medical
      treatments or deep brain stimulation for patients with generalised dystonia.

PMID- 16987734
TI  - Deep brain stimulation in headache.
AB  - BACKGROUND: The therapeutic use of deep brain stimulation to relieve intractable
      pain began in the 1950s. In some patients, stimulation of the periaqueductal grey
      matter induced headache with migrainous features, indicating a pathophysiological
      link between neuromodulation of certain brain structures and headache. RECENT
      DEVELOPMENTS: Neuroimaging studies have revealed specific activation patterns in
      various primary headaches. In the trigeminal autonomic cephalgias, neuroimaging
      findings support the hypothesis that activation of posterior hypothalamic neurons
      have a pivotal role in the pathophysiology and prompted the idea that
      hypothalamic stimulation might inhibit this activation to improve or eliminate
      the pain in intractable chronic cluster headache and other trigeminal autonomic
      cephalgias. Over the past 6 years, hypothalamic implants have been used in
      various centres in patients with intractable chronic cluster headache. The
      results are encouraging: most patients achieved stable and notable pain reduction
      and many became pain free. All deep-brain-electrode implantation procedures carry
      a small risk of mortality due to intracerebral haemorrhage. Before implantation,
      all patients must undergo complete preoperative neuroimaging to exclude disorders
      associated with increased haemorrhagic risk. No substantial changes in
      hypothalamus-controlled functions have been reported during hypothalamic
      stimulation. Hypothalamic stimulation may also be beneficial in patients with
      SUNCT (short-lasting, unilateral, neuralgiform headache attacks with conjunctival
      injection and tearing)--a disorder with close clinical and neuroimaging
      similarities to the cluster headache. WHERE NEXT?: Neuroimaging findings in
      patients undergoing posterior hypothalamic stimulation have shown activation of
      the trigeminal nucleus and ganglion. This evidence supports the hypothesis that
      hypothalamic stimulation exerts its effect by modulating the activity of the
      trigeminal nucleus caudalis, which in turn might control the brainstem
      trigeminofacial reflex--thought to cause cluster headache pain. Future studies
      might determine whether other areas of the pain matrix are suitable targets for
      neuromodulation in patients with cluster headache who do not respond to
      hypothalamic modulation.

PMID- 16987735
TI  - Less is more: pathophysiology of dopaminergic-therapy-related augmentation in
      restless legs syndrome.
AB  - Therapy-related augmentation of the symptoms of restless legs syndrome (RLS) is
      an important clinical problem reported in up to 60% of patients treated with
      levodopa and, to a lesser extent, with dopamine agonists. The efficacy of low
      dose dopaminergic drugs for RLS has been established, but the mode of action is
      unknown. Here, we review the existing data and conclude that augmentation is a
      syndrome characterised by a severely increased dopamine concentration in the CNS;
      overstimulation of the dopamine D1 receptors compared with D2 receptors in the
      spinal cord may lead to D1-related pain and generate periodic limb movements;
      iron deficiency may be a main predisposing factor of augmentation, probably
      caused by a reduced function of the dopamine transporter; therapy with levodopa
      or dopamine agonists should remain at low doses and; iron supplementation and
      opiates are the therapy of choice to counter augmentation.

PMID- 16987736
TI  - Infectious causes of multiple sclerosis.

PMID- 16987737
TI  - Benign pediatric localization-related epilepsies. Part I. Syndromes in infancy.
AB  - There is currently increasing interest in identifying and classifying pediatric
      benign epilepsy syndromes and recently several new syndromes have been
      recognized. Benign epilepsy syndromes, by definition, occur in children with
      normal developmental history, respond well to therapy, and remit without
      sequelae. The large majority of children with benign epilepsy syndromes follow a
      truly benign course. The concept of benign epilepsy syndromes has, however, been
      challenged by the minority of patients who continue to have seizures despite
      therapy, develop new seizures after initial remission, or exhibit
      neuropsychological abnormalities. Without long-term follow-up, benignity can not
      be truly ascertained a priori. Thus it may be preferable to use the terms
      possible and probable before the name of a specific syndrome until such time that
      the diagnosis of a definite benign syndrome is confirmed on long-term follow-up.
      In this review of the pediatric benign localization-related epilepsy syndromes,
      we address the concept of benignity and the process of diagnosis of a benign
      epilepsy syndrome. In addition we review the epidemiology, clinical
      manifestations, EEG findings, work-up, diagnostic criteria, differential
      diagnosis, genetics, management and prognosis of benign infantile familial
      convulsions, benign partial epilepsy in infancy with complex partial seizures,
      benign partial epilepsy in infancy with secondarily generalized seizures, benign
      infantile convulsions associated with mild gastroenteritis, and benign infantile
      focal epilepsy with midline spikes and waves during sleep.

PMID- 16987738
TI  - Fewer women receive tertiary care for epilepsy in Kerala State, India.
AB  - PURPOSE: The stigma attached to epilepsy often restricts early diagnosis and
      optimal care, particularly among the underprivileged. We aimed to ascertain any
      gender bias in the utilization of services for epilepsy in a tertiary and
      community care facility in Kerala State, India. METHODS: The R. Madhavan Nayar
      Center for Comprehensive Epilepsy Care (RMNC) is a leading tertiary care facility
      in South India. The District Mental Health Program (DMHP) is a community-based
      care facility that provides medical consultation and anti-epileptic drugs (AED)
      free of charge. We analyzed the sex ratio (SR) - number of women per one thousand
      men - of all registrations in these centers according to year of registration,
      age, religion, income, distance from domicile to the center, and religion.
      RESULTS: The SR in the RMNC (1976-2004, n = 12354) was 729. At RMNC, age-specific
      SR increased up to the 3rd decade (864), and progressively declined beyond 50
      years. The SR was lower for those domiciliated at more than 200 km from the
      center when compared to others. The SR at the DMHP (1999-2004, n = 221) was high
      (1125). The age-specific SR at DMHP showed two peaks at 21-30 years (1368) and 51
      60 years (2333). CONCLUSION: Fewer women with epilepsy (particularly in lower
      socioeconomic groups) receive tertiary care in this state, in spite of a higher
      SR in the community (907 for epilepsy and 1058 for all population). The tertiary
      treatment gap is wider for women over 30 years (particularly over 50 years), when
      their longer life expectancy is also taken into consideration.

PMID- 16987739
TI  - Combining advanced neuroimaging techniques in presurgical workup of non-lesional
      intractable epilepsy.
AB  - PURPOSE: The rationale for this case report is to assess the degree of congruency
      between the results of several advanced functional, metabolic, and structural
      neuroimaging techniques used in patients with MRI-negative focal epilepsy.
      METHODS: We investigated the presurgical evaluation and post-operative outcome of
      a patient with intractable, extratemporal epilepsy. Because the habitual seizures
      in this patient could be easily induced, six, advanced, neurodiagnostic
      techniques were successively applied (SISCOM, ictal FDG-PET, ictal fMRI,
      postictal diffusion-weighted imaging, voxel-based morphometry, and MRS imaging).
      RESULTS: The findings for the neuroimaging methods investigated, within the left
      central region, were fairly congruent. Subsequent, invasive EEG recordings
      revealed a seizure-onset zone at the site where most of the neuroimaging had
      shown abnormal findings. The surgical removal of the epileptogenic zone, as
      defined by concordant neuroimaging and SEEG data, resulted in seizure-free
      postoperative outcome. Histopathological findings revealed mild focal cortical
      dysplasia. CONCLUSION: Great efforts should be made to combine most of the
      advanced neuroimaging methods in the preoperative assessment of non-lesional
      epilepsy surgery candidates.

PMID- 16987740
TI  - Status epilepticus in a patient with fragile X syndrome: electro-clinical
      features and peri-ictal neuroimaging.
AB  - Fragile X syndrome (Fra-X) is a common cause of mental retardation that can be
      associated with partial epilepsy characterized by a variety of electro-clinical
      features. A wide spectrum of interictal activities are reported, although no data
      regarding ictal EEG activity have as yet been published. Drug-resistant seizures
      are uncommon, and the occurrence of clustering seizures or status epilepticus has
      only been reported anecdotally. We describe a Fra-X patient with refractory
      partial epilepsy related to a malformation of cortical development who
      experienced a partial status epilepticus that was well documented by video-EEG
      and MRI. We report the electro-clinical features and peri-ictal neuroimaging
      data.

PMID- 16987741
TI  - NARP syndrome and adult-onset generalised seizures.
AB  - The neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) syndrome
      is a maternally inherited disorder attributable to a heteroplasmic mtDNA point
      mutation. Catastrophic epilepsy may accompany severe, early onset forms of NARP,
      but seizures seem to be rare in cases with adolescent and adult onset. We
      describe a patient who developed clumsiness and visual problems in her teens. She
      had no clinical seizures but an EEG showed generalized spike and wave discharges.
      At this time the patient remained without a specific diagnosis. At the age of 21,
      the patient developed progressive ataxia and she also experienced a tonic-clonic
      status epilepticus. Further examinations revealed NARP syndrome. EEG
      abnormalities may precede adult onset seizures in the NARP syndrome.

PMID- 16987742
TI  - Intractable cryptogenic frontal lobe epilepsy in a patient with MURCS
      association.
AB  - The MURCS association is a rare, nonrandom association of mullerian duct aplasia,
      renal aplasia and cervicothoracic somite dysplasia. The etiology is unknown.
      Although it is usually a sporadic disorder, familial cases with uterovaginal
      anomalies have been reported. Occasionally, it may be accompanied by
      abnormalities involving various other organs or systems. Malformations related to
      the central nervous system are very rare and the presence of seizures has not
      been reported previously. We present a 26-year-old female with MURCS association
      who had late onset, drug resistant partial seizures presumably originating in the
      frontal lobe.

PMID- 16987743
TI  - Gelastic seizures involving the right parietal lobe.
AB  - Gelastic seizures have been described in various epilepsies arising from the
      temporal or frontal lobes, although the most commonly encountered form is related
      to the presence of an hypothalamic hamartoma. We report a patient with gelastic
      seizures involving the right parietal lobe. Our patient, a 32-year-old man,
      underwent video-EEG monitoring, interictal and ictal brain SPECTs during gelastic
      seizures. Subtraction ictal SPECT co-registered to MRI (SISCOM), was performed to
      localize any ictal hyperperfusion during these gelastic seizures. The seizures
      consisted of brief staring followed by smiling and laughing.
      Electroencephalography during the gelastic seizures showed rhythmic sharp waves
      in the right parietal lobe. SISCOM showed ictal hyperperfusion in the right
      parietal lobe and medial portions of right cerebellum. Our findings suggest that
      the right parietal lobe may actively participate in the particular epileptogenic
      network generating gelastic seizures.

PMID- 16987744
TI  - Levetiracetam-induced myoclonic status epilepticus in myoclonic-astatic epilepsy:
      a case report.
AB  - We report on a 3-year-old boy with myoclonic-astatic epilepsy who developed
      myoclonic status epilepticus with continuous twitching of the face and
      unresponsiveness under monotherapy with levetiracetam. Recently, a nonconvulsive
      status epilepticus in an adult epilepsy patient has also been described. Our
      observation points to the possibility of a causal relationship between the
      induction of myoclonic status by levetiracetam in certain patients with Doose's
      syndrome. However, a spontaneous evolution cannot be excluded. Levetiracetam is a
      well-known drug for the control of myoclonic seizures. A controlled study would
      provide a better understanding of any possible aggravating role in certain forms
      of myoclonic-astatic epilepsy.

PMID- 16987745
TI  - Vasovagal syncope misdiagnosed as epilepsy for 17 years: prime importance of
      clinical history.
AB  - Distinguishing epilepsy from syncope often can be challenging. We report a case
      of a 20-year-old patient with presumed refractory epilepsy since the age of 3
      years. Although the clinical suspicion of syncope was raised at the age of 9
      years, key historic features were not identified, cardiac work-up was not pursued
      and despite lack of electrographic evidence of epilepsy, he received
      anticonvulsant treatment. During his presurgical evaluation for "refractory
      epilepsy", one typical event was captured that was associated with asystole and
      normal electroencephalogram. The diagnosis of vasodepressor syncope was made and
      anticonvulsant medication was discontinued. With this case report, we would like
      to emphasize the importance of a meticulous history and the need to perform
      continuous video electroencephalographic with simultaneous electrocardiographic
      recordings in the evaluation of paroxysmal events with atypical presentation.
      [Published with video sequences].

PMID- 16987746
TI  - Senile myoclonic epilepsy in Down syndrome: a video and EEG presentation of two
      cases.
AB  - Myoclonic epilepsy is being increasingly recognized as a late-onset complication
      in middle-aged or elderly patients with Down syndrome, in association with
      cognitive decline. We show video and EEG recordings of two patients, both aged 56
      years, diagnosed with this condition. At onset, myoclonic epilepsy in elderly DS
      patients may resemble, in its clinical expression, the classical juvenile
      myoclonic epilepsy with the characteristic occurrence of jerks on awakening. It
      is clearly associated with an Alzheimer-type dementia, and may also occur in non
      DS patients with Alzheimer's disease: hence the possible denomination of "senile
      myoclonic epilepsy". [Published with video sequences].

PMID- 16987747
TI  - Postictal behaviour in temporal lobe epilepsy.
AB  - Postictal phenomena such as nose-wiping, coughing and hypersalivation are
      believed to reflect a purposeful reaction to hypersecretion after regaining
      consciousness following a complex partial seizure, and are very common in
      patients with temporal lobe epilepsy, particularly in mesial temporal lobe
      epilepsy. Nose-wiping is usually performed with the hand ipsilateral to the side
      of seizure onset. Our patient illustrates an unusual, exaggerated postictal
      behaviour consisting of long-lasting nose-wiping, coughing and guttural sounds
      following a complex partial seizure due to right mesial temporal lobe epilepsy.
      [Published with video sequences].

PMID- 16987748
TI  - Pilomotor seizures associated with sequential changes in magnetic resonance
      imaging.
AB  - Piloerection is rarely described in seizures. This symptom has been most
      frequently observed in patients with temporal lobe epilepsy and is rarely the
      principal clinical feature of seizures. No specific etiology of epilepsy
      associated with pilomotor seizures has been reported. We present the first case
      of a patient who experienced sudden and transitory epilepsy with pilomotor
      seizures occurring several times a day for months, and associated with sequential
      changes of the left hippocampus demonstrated by magnetic resonance imaging.
      [Published with video sequences].

PMID- 16987749
TI  - Dermatopontin, a novel player in the biology of the extracellular matrix.
AB  - Dermatopontin is a widely distributed small molecular weight protein in the
      extracellular matrix (ECM) and today its homologues are known in five mammals and
      several invertebrates. The structures of these homologues are relatively well
      conserved among the species. In the skin, dermatopontin is located mainly on the
      surface of the collagen fibers. It is found in the conditioned medium and also in
      the cytoplasm of cultured fibroblasts. Early studies focused on ECM assembly
      (collagen fibrillogenesis) and interactions (with the proteoglycan decorin).
      Subsequently, a targeted disruption of dermatopontin resulted in a phenotype
      similar to Ehlers-Danlos syndrome. In addition, a cell adhesion activity of this
      protein for dermal fibroblasts and several other cells was found, and this
      activity might suggest this protein's involvement in wound healing. The
      expression of dermatopontin around an infarct zone of experimental myocardial
      infarction may support this possibility. In invertebrates, dermatopontin
      homologues act mainly as adhesion/agglutination molecules. In addition, we found
      that transforming growth factor-beta1 interacts with dermatopontin and the
      function of this cytokine is modified by dermatopontin. Recently, the involvement
      of this protein in cell proliferation has been indicated. In this review we
      describe the reported functions of this protein and speculate on the multiple
      roles of this largely uncharacterized matrix molecule.

PMID- 16987750
TI  - Tissue engineered cartilage integration to live and devitalized cartilage: a
      study by reflectance mode confocal microscopy and standard histology.
AB  - This study investigated the in vivo formation of engineering cartilage within
      living or devitalized cartilage discs using reflectance mode confocal microscopy
      and conventional light microscopy. Pig articular chondrocytes were suspended in
      fibrin glue and placed between two cartilage discs. Four experimental groups were
      prepared: in groups 1 and 2, the cell-hydrogel composite was placed between two
      live or between two devitalized cartilage discs, respectively; in groups 3 and 4,
      acellular fibrin glue was placed between two live or between two devitalized
      cartilage discs, respectively. Samples were implanted in the back of nude mice
      and analyzed after 2, 5, and 8 weeks. Results showed that engineered cartilage
      seems to grow more homogenously when the cell-seeded gel was placed between
      devitalized cartilages than when it was placed between live cartilage matrices.
      Confocal microscopy provides valuable information on the integration of tissue
      engineered cartilage with native tissue and could be useful for nondestructive
      imaging in vivo.

PMID- 16987751
TI  - Expression, content, and localization of insulin-like growth factor I in human
      achilles tendon.
AB  - In animals insulin-like growth factor I (IGF-I) stimulates collagen production by
      fibroblasts and is expressed in tendons together with its binding protein 4
      (IGFBP-4). However, the presence of IGF-I and IGFBP-4 in human tendon tissue is
      not described. Tissue IGF-I content was examined by immunoflourometric assay,
      real-time PCR, and immunohistochemistry used to localize and determine expression
      of IGF-I and IGFBP-4 in 6 postmortem human Achilles tendons. Tendon tissue
      concentrations of IGF-I were found to be 0.53 +/- 0.10 ng/g. Furthermore, we
      demonstrated that IGF-I and IGFBP-4 are localized around the tendon fibroblasts
      and that mRNA for IGF-I and IGFBP-4 can be determined in human tendon tissue. The
      present study adds support for the roles of IGF-I and IGFBP-4 in the regulation
      of tendon adaptive responses to mechanical loading.

PMID- 16987752
TI  - Biaxial strain effects on cells from the inner and outer regions of the meniscus.
AB  - During knee joint loading, the fibrocartilaginous menisci experience significant
      spatial variations in mechanical stimuli. Meniscus cells also exhibit significant
      variations in biosynthesis and gene expression depending on their location within
      the tissue. These metabolic patterns are consistent with a more chondrocytic
      phenotype for cells located within the avascular inner two-thirds compared with a
      more fibroblastic phenotype for cells within the vascularized outer periphery.
      The spatial distribution of cell biosynthesis and gene expression patterns within
      the meniscus suggest that cells may exhibit intrinsically different responses to
      mechanical stimuli. The objective of our study was to test for intrinsic
      differences in the responsiveness of these meniscus cell populations to an
      equivalent mechanical stimulus. Cellular biosynthesis and gene expression for
      extracellular matrix proteins in isolated inner and outer meniscus cells in
      monolayer were quantified following cyclic biaxial stretch. The results
      demonstrate that inner and outer meniscus cells exhibit significant differences
      in matrix biosynthesis and gene expression regardless of stretching condition.
      Both inner and outer meniscus cells responded to stretch with increased nitric
      oxide production and total protein synthesis. The results suggest that inner and
      outer meniscus cells may respond similarly to biaxial stretch in vitro with
      measures of biosynthesis and gene expression.

PMID- 16987753
TI  - Mapping lubricin in canine musculoskeletal tissues.
AB  - Lubricin, also known as superficial zone protein or PRG4, has many distinct
      biological functions, including lubrication, antiadhesion, and as a regulator of
      cell growth. This study investigated lubricin in canine musculoskeletal tissues
      using RT-PCR and immunohistochemistry. One or more variants were noted in canine
      flexor digitorum profundus (FDP) tendon, Achilles tendon, patellar tendon, A2
      pulley, anterior cruciate ligament (ACL), knee lateral collateral ligament (LCL),
      articular cartilage, meniscus, muscle, and skin. We found 6 N-terminal lubricin
      splicing variants. The variants with larger sizes were identified in FDP tendon,
      ACL, LCL, A2 pulley, and cartilage. Lubricin was distributed both on the tissue
      surfaces and at the interface of fiber bundles within tissues, but this
      distribution varied by tissue type. We conclude that lubricin is present in many
      tissues; variations in splicing and physical distribution suggest that the
      variants of lubricin may play different roles in different locations.

PMID- 16987754
TI  - Pulsed electromagnetic fields accelerate apoptotic rate in osteoclasts.
AB  - Selective control of cell function by applying specifically configured, low
      energy, time-varying electromagnetic fields (EMF) has added a new, exciting
      dimension to biology and medicine. However, the mechanism involved is less clear.
      In our study, we investigated the effect of pulsed electromagnetic fields (PEMF)
      on induction of osteoclasts apoptosis. A statistically significant increase of
      apoptotic rate in osteoclasts (48 hr after isolation) was found when exposed to
      7.5 Hz PEMF with induced electric fields intensity of 3.0 muv/cm for 8 (105%, p <
      0.001) and 16 hr (30%, p < 0.05). However, exposure of osteoclasts to PEMF for
      only 1 hr showed no statistically significant differences. These findings suggest
      that PEMF have the ability to speed up apoptosis of osteoclasts derived from
      primary osteoblasts and bone marrow cells cocultures. This in vitro study,
      therefore, could be considered as groundwork for in vivo PEMF applications on
      some osteoclasts-associated bone diseases such as osteoporosis.

PMID- 16987755
TI  - False-positive beta-galactosidase staining in osteoclasts by endogenous enzyme:
      studies in neonatal and month-old wild-type mice.
AB  - Escherichia coli beta-galactosidase (beta-gal), encoded by the lacZ gene, has
      become an essential tool in studies of gene expression and function in higher
      eukaryotes. lac-Z is widely used as a marker gene to detect expression of
      transgenes or Cre recombinase driven by tissue-specific promoters. The timing and
      location of promoter activity is easily visualized in whole embryos or specific
      tissues using the cleavable, chromogenic substrate, 5-bromo-4-chloro-3-indolyl-D
      galactopyranoside (X-gal). The tissue specificity of promoters in transgenic
      constructs is routinely tested by using a promoter of choice to drive lacZ.
      Alternatively, the targeted expression of Cre recombinase to perform in vivo
      recombination of loxP sites can be visualized by beta-gal staining in mice
      carrying a Cre-activated lacZ transgene, such as the ROSA26 strain. In the course
      of our investigations, we examined beta-gal activity in bone tissue from
      genetically normal mice using standard detection methodology and found very high
      endogenous activity in bone-resorbing osteoclasts. This was true in frozen,
      paraffin, and glycol methacrylate sections. X-gal staining colocalized with the
      osteoclast marker, tartrate-resistant acid phosphatase (TRAP). beta-gal activity
      was present in osteoclasts in long bones, in the mandible, and in both neonatal
      and more mature animals. We present this brief article as a caution to those
      testing genetic models of skeletal gene expression using beta-gal as a marker
      gene.

PMID- 16987756
TI  - Change in decorin during aging of rat placenta.
AB  - By immunohistochemistry, with or without chondroitinases, decorin was found to be
      distributed in the extracellular matrix of chorionic villi and amnia. The
      strength of staining intensified with increasing gestational age. Decorin was
      isolated from the placenta of 13- to 20-day-old pregnant rats and identified by
      Western blotting, using an antidecorin core protein antibody. The molecular
      weight of decorin is approximately 100 kDa, whereas the respective figures for
      the core protein treated with chondroitinase (chase) ABC and with chase B are
      approximately 40 kDa and 43 kDa. The difference in the molecular weight between
      the core protein with chase ABC and B suggests that the glycosaminoglycan (GAG)-
      base structure on the core protein was chondroitin sulfate (CS) without dermatan
      sulfate (DS). The decorin content and the proportion of CS to DS in GAG increased
      with age. We concluded that the age-related changes in the GAG chain may be
      related to specific functional properties and may have a crucial role in
      placental tissue organization.

PMID- 16987757
TI  - Transient exposure of fibroblast growth factor-2 induced proliferative but not
      destructive changes in mouse knee joints.
AB  - Fibroblast growth factor-2 (FGF-2) has the potential to regenerate damaged
      articular cartilage tissue due to its exerting anabolic effects on chondrocytes.
      However, FGF-2 is involved in pathogenesis of rheumatoid arthritis, where the
      joint is destructed. The study aims at clarifying the effects of FGF-2 on joints.
      When radiolabeled FGF-2 was injected into knee joints of C57Bl/10 mice, a
      transient binding was observed in the superficial and intermediate zones of the
      articular cartilage as well as in the synovium and perichondrium. An FGF-2
      injection (5 microg) caused synovial hyperplasia adjacent to the articular
      cartilage on day 7, cartilage formation adjacent to the articular cartilage on
      day 14, and osteophyte on day 21. The intensity of safranin-O staining of the
      articular cartilage increased on day 14. These changes were dose-dependent. No
      destructive changes in the joints were observed. In a joint, transient exposure
      of FGF-2 caused proliferative changes, but not destructive changes.

PMID- 16987763
TI  - Ocular adnexal Langerhans cell histiocytosis clinical features and management.
AB  - PURPOSE: To review the clinical features, investigations, management, and
      outcomes of Langerhans cell histiocytosis (LCH) with ocular adnexal involvement.
      MATERIALS AND METHODS: Retrospective, non-comparative, chart review of 30
      patients with LCH involving the ocular adnexa treated at 6 major Australian
      hospitals. Clinical features, imaging findings, treatment, local and distant
      recurrence and outcome were evaluated. RESULTS: Twenty-four patients (80%) were
      male with a mean age of presentation of 9.5 years. Females presented at an
      earlier age (mean age 4.1 years) with more severe involvement. Eighty percent of
      the cases presented with periorbital swelling. Computed tomography usually showed
      destructive osteolytic lesions centred on the frontal bone. Twenty-four patients
      (80%) had unifocal, unisystem disease. From this group, none of 13 treated with
      excision alone had recurrence whereas 2 of 6 treated with excision followed by
      chemotherapy recurred. CONCLUSIONS: Unifocal, unisystem LCH often presents to the
      ophthalmologist and can usually be diagnosed on clinical and imaging grounds.
      Computed tomography and magnetic resonance imaging are complementary imaging
      studies. Biopsy is essential to confirm diagnosis. Unifocal, unisystem disease
      can be treated with local excision and curettage. Incomplete excision, recurrent
      disease or multifocal disease may require systemic chemotherapy.

PMID- 16987764
TI  - Towards an understanding of congenital ptosis.
AB  - This paper examines the developmental substrate for congenital ptosis with
      particular emphasis on the transcription factors that are thought to be involved.
      We summarize my research findings and present a review of the relevant
      literature.

PMID- 16987765
TI  - Orbital exenteration--a retrospective study over an 11 year period analyzing all
      cases from a single unit.
AB  - PURPOSE: A retrospective analysis of all cases of orbital exenteration performed
      at the National Scottish Ocular Oncology Center over an 11 year period. METHODS:
      We sought all exenteration cases (1993-2003) from ocular oncology and
      oculoplastic databases. Fifteen exenterations were performed. One case record was
      irretrievable. Clinicopathological features and outcome of 14 patients were
      analyzed. All operations were performed by the same consultant. RESULTS: The male
      to female ratio was 1:1 and the average age at surgery was 66 years. There was a
      left sided predominance of pathology demonstrated (right to left orbit ratio was
      1:1.3. The average follow up period postsurgery was 35 months. The most common
      underlying diagnosis was malignant melanoma (9/14). Ocular/orbital discomfort was
      the most frequent presenting symptom (7/14); a mass lesion (10/14) was the most
      common presenting sign. The average duration of symptoms/signs prior to tertiary
      institution referral was 10.9 months (range: 0.5-60 months). Exenteration was
      performed on average 39.7 months (range: 0.13-204) after initial tertiary center
      presentation. This included patients managed from the outset who failed
      treatment(s) and then required exenteration. The eyelids were sacrificed in ten
      cases (10/14). Sockets were lined with eyelid skin (4/10), split skin (thigh)
      (3/10) or healed secondarily (7/10). Thirteen cases (13/14) had clear
      histological margins. The average post operative stay was 8.3 days. The most
      common complication was socket fistula formation (7/14). Ethmoid sinuses were
      always involved. The average time to fistula development was 4.9 months (sockets
      lined by skin = 2.2 months compared with sockets left to heal secondarily = 6.9
      months). The majority of patients wore occlusive shields long term. CONCLUSION:
      The most common pathology necessitating exenteration was malignant melanoma. Most
      patients presented with a mass lesion. Histological tumor free margins were
      obtained in thirteen of fourteen cases. The most common complication was socket
      fistula formation.

PMID- 16987766
TI  - Amniotic membrane transplantation versus mucous membrane grafting in anophthalmic
      contracted socket.
AB  - PURPOSE: Amniotic membrane has been successfully used for treatment of various
      ocular surface disorders, but there have been no published reports untill now
      regarding its use in the treatment of contracted socket. The aim of this study
      was to determine the role of amniotic membrane and to compare the results with
      mucous membrane grafting in anophthalmic contracted socket. METHODS: A
      prospective study of 20 eyes with mild to moderate anophthalmic contracted socket
      was carried out. Two groups, each with 10 eyes, were formed randomly. Group A
      underwent amniotic membrane transplantation, and Group B mucous membrane
      grafting. Prosthesis was fitted 6-8 weeks post operatively. The volume and
      fornices' length was compared preoperatively and at 3, 6 and 12 months
      postoperatively. RESULTS: Apart from measurements, patient satisfaction was an
      important criteria in defining the success of the procedure. At the end of 12
      months, the relative increase between the 2 groups in the fornix and volume
      measurements were statistically significant (SF-0.001,IF-0.001,V-0.001) with
      better patient comfort in group A. There was no statistical significance
      regarding the rate of complications between both the groups (p = 0.29).
      CONCLUSION: Amniotic membrane emerges as a viable alternative to established
      mucous membrane grafting as it causes less patient morbidity, faster recovery and
      better fitting of prosthesis. No contracture is observed with amniotic membrane
      as against mucous membrane. It is cheap and easily available and has no
      significant complications associated with it.

PMID- 16987767
TI  - Precaruncular periosteal anchor of medial rectus, a new technique in the
      management of complete external third nerve palsy.
AB  - Management of complete external third nerve palsy is a challenge to a
      strabismologist; as four of six extra-ocular muscles are affected, it leaves eye
      in fixed hypotropic and exotropic position (Srivastava et al., 2004). Although
      numerous surgical procedures have been described, none has been found to be ideal
      for all cases. Horizontal supramaximal recession-resection procedure may work in
      cases having some function of medial rectus (Harley, 1980). In cases of complete
      external palsy, anchoring of globe to periosteum of medial orbital wall using
      different structures has been described (Villasenor Solares et al., 2000; Bicas,
      1991; Salazar-Leon et al., 1998), as recession-resection may result in large
      residual deviation and/or eye drifts back to abducted position due to unopposed
      lateral rectus action (Von Noorder, 1996). These anchoring procedures are with
      associated problems of skin incision, thigh surgery or loss of superior oblique
      function (Villasenor Solares et al., 2000; Bicas, 1991; Salazar-Leon et al.,
      1998). We describe a new and safe technique for management of complete external
      third nerve palsy by anchoring insertion of medial rectus to medial wall
      periosteum, posterior to posterior lacrimal crest, along with supra maximal
      recession of lateral rectus.

PMID- 16987768
TI  - Palpebral dimensions in Brazilian children: assessment based on digital images.
AB  - PURPOSE: To determine palpebral dimensions and development in Brazilian children
      using digital images. METHODS: An observational study was performed measuring
      eyelid angles, palpebral fissure area and interpupillary distance in 220 children
      aged from 4 to 72 months. Digital images were obtained with a Sony Lithium movie
      camera (Sony DCR-TRV110, Brazil) in frontal view from awake children in primary
      ocular position; the object of observation was located at pupil height. The
      images were saved to tape, transferred to a Macintosh G4 (Apple Computer Inc.,
      USA) computer and processed using NIH 1.58 software (NTIS, 5285 Port Royal Rd.,
      Springfield, VA 22161, USA). Data were submitted to statistical analysis.
      RESULTS: All parameters studied increased with age. The outer palpebral angle was
      greater than the inner, and palpebral fissure and angles showed greater changes
      between 4 and 5 months old and at around 24 to 36 months. CONCLUSION: There are
      significant variations in palpebral dimensions in children under 72 months old,
      especially around 24 to 36 months.

PMID- 16987769
TI  - Surgical management of the severely contracted socket following reconstruction.
AB  - PURPOSE: To present a surgical technique for the early maintenance of the
      severely contracted socket following reconstruction. METHODS: Two patients with
      severely contracted sockets following multiple procedures and recurrent failure
      were identified over a 1 year period. Following fornix and eyelid reconstruction,
      silicone fixative was injected into the fornix through a standard conformer. The
      silicone fixed around a pre-placed K-wire passed from the lateral orbital rim to
      the posterior lacrimal crest. Both silicone and wire were removed at 3 months.
      RESULTS: Both patients were able to wear and maintain an acceptable prosthesis
      following the surgical procedure. CONCLUSION: This is a safe and effective method
      for the early maintenance of a severely contracted socket. This technique
      minimizes cheesewiring or extrusion and avoids damage to superior and inferior
      muscles and structures.

PMID- 16987770
TI  - Orbital and eyelid manifestations of xanthogranulomatous diseases.
AB  - Erdheim-Chester disease, adult periocular xanthogranuloma, juvenile
      xanthogranuloma, and necrobiotic xanthogranuloma are presumed to be separate
      disease entities, but they are often confused clinically because of their similar
      presentations and histopathology. To further describe the xanthogranulomatous
      diseases and to identify possible pitfalls in their diagnoses, we retrospectively
      reviewed charts from 1998 to 2001 for all patients with biopsy-proven
      xanthogranulomatous process of the eyelid and/or orbit. We found 2 patients
      diagnosed with adult periocular xanthogranuloma and 1 with Erdheim-Chester
      disease, each case initially misdiagnosed. Careful review of the clinical
      manifestations, histopathological review of all previous biopsy specimens, and
      repeat biopsy aided in the correct diagnosis and management of disease in these 3
      patients.

PMID- 16987771
TI  - Intramuscular lipoma of the superior oblique muscle.
AB  - We describe a rare intramuscular infiltrating lipomatous tumor affecting the
      superior oblique muscle. A 37-year-old female presented with eyelid swelling,
      proptosis and motility disturbance. Imaging studies revealed enlargement of the
      superior oblique muscle with a fat-density infiltrating lesion within its belly.
      The clinical and radiologic findings suggested a cystic or necrotic lesion.
      Biopsy showed an infiltrative tumor consisting of adipocytes with included
      degenerated muscle fibers. Histologic features were consistent with a benign
      intramuscular lipoma, rather than the more aggressive well-differentiated
      liposarcoma. A review of the literature found three previously described
      periorbital cases, two in the eyelid, and one in the anterior orbit. Lipomas are
      common tumors that usually do not cause functional impairment but are very rare
      in the orbit. Intramuscular lipoma is a rare subtype that can result in
      significant morbidity. Enlargement of an extraocular or periorbital muscle with a
      low-density infiltrating lesion should raise suspicion for this unusual tumor.

PMID- 16987772
TI  - Cutaneous embryonal rhabdomyosarcoma presenting as a nodule on cheek; a case
      report and review of literature.
AB  - We report a case of primary cutaneous rhabdomyosarcoma, solid embryonal type,
      presenting as a rapidly enlarging nodule on the right cheek of a 7-year-old boy.
      This lesion had begun as a pea-sized nodule 8 months previously, and, with
      suspected abscess, had been incised. It recurred 2 months later; at that time,
      incisional biopsy was consistent with malignant round cell tumor. Wide local
      excision of the tumor was then completed. Subsequent immunohistochemical staining
      with desmin and myoglobin confirmed embryonal rhabdomyosarcoma. The patient
      underwent radiation therapy followed by chemotherapy and continues to be disease
      free at 14 months after his wide local excision. Rhabdomyosarcoma presenting as a
      dermal nodule is rare. It usually presents as an asymptomatic papule without
      distinctive clinical features and therefore may result in delayed diagnosis
      unless a biopsy is performed.

PMID- 16987773
TI  - Orbital neurofibroma presenting with a negative Hounsfield unit on computerized
      tomography.
AB  - PURPOSE: To report a case of diffuse orbital neurofibroma which displayed an
      unusual computed tomography (CT) feature. METHODS: Results of ocular examination,
      orbital CT examination and pathological findings in a patient with a space
      occupying orbital lesion are presented. RESULTS: Orbital CT evaluation of a male
      patient, aged one and a half years old, revealed a right orbital lesion with a
      strongly negative value in Hounsfield units. The preoperative diagnosis was a
      dermoid cyst. An anterior orbitotomy was performed, and the surgical specimen
      demonstrated a typical plexiform neurofibroma with routine hematoxylin and eosin
      staining and immunohistochemical studies. CONCLUSIONS: Plexiform orbital
      neurofibromas may demonstrate a negative Hounsfield value on CT examination.

PMID- 16987774
TI  - Oncocytoma of the lacrimal gland: case report and review of the literature.
AB  - OBJECTIVE: Oncocytomas of the lacrimal gland are rare tumors. We report the
      eighth case in the literature. DESIGN: Interventional case report and literature
      review. INTERVENTION: Complete ophthalmologic and systemic examination followed
      by excisional biopsy and histopathologic examination. RESULTS: A 40-year-old
      Hispanic woman was evaluated for a right-sided upper eyelid edema and pain on
      ocular motility. A month earlier an outside ophthalmologist had performed a
      conjunctival biopsy that disclosed chronic inflammation. Computed tomography and
      magnetic resonance imaging of brain and orbit demonstrated a right intraorbital
      extraconal soft tissue density mass that involved the lacrimal gland, upper
      eyelid and encroached both the superior oblique and superior rectus muscles.
      Histopathology showed a benign oncocytoma that replaced most of the lacrimal
      gland. CONCLUSION: Although rare, oncocytomas should be included in the
      differential diagnosis of any lacrimal gland tumors.

PMID- 16987775
TI  - Lacrimal sac metastases from renal cell carcinoma.
AB  - PURPOSE: To report the first case of metastasis from renal cell carcinoma to the
      lacrimal sac and review the therapeutic options. METHODS: We have reviewed the
      case of a woman who was operated on for a renal cell carcinoma that developed
      epiphora and a lacrimal sac tumor, which corresponded to a metastasis from her
      previous tumor. Although renal cell carcinoma shows a great tendency for distant
      metastasis, this is the first reported case of metastasis to the lacrimal sac.
      RESULTS: We comment on the rarity of the case and on the therapeutic alternatives
      for these cases according to the reviewed literature. CONCLUSION: Metastasis to
      the lacrimal sac are rather infrequent and should be borne in mind on the
      appearance of a tumor in this location in people with a history of malignancy.

PMID- 16987776
TI  - Orbital implant exposure treatment with porcine dermal collagen patching.
AB  - PURPOSE: To present a small case series of orbital implant exposures treated with
      porcine dermal collagen (Permacol, Tissue Science Laboratories PLC, Aldershot,
      Hants, UK) patching. METHODS: A retrospective chart review of three cases of
      orbital implant exposure treated with Permacol patching. RESULTS: Three cases
      were identified. There were 4 operative episodes of Permacol patching (one socket
      had two attempts at permacol patching). In all 4 cases the patch rapidly failed
      and melted away leaving behind the orbital implant exposure. All 3 patients
      required implant removal. CONCLUSIONS: Orbital implant exposure remains a major
      long-term complication of evisceration and enucleation procedures. On the basis
      of our experience, we would not recommend using Permacol as a non-autologous
      material for covering exposed Medpor (Medpor, Porex Surgical, Atlanta, Georgia,
      USA) orbital implants. Further study is required to fully assess the safety and
      efficacy profile of Permacol in socket surgery.

PMID- 16987777
TI  - Structure-based modulation of inhibition of return is triggered by object
      internal but not occluding shape features.
AB  - When attention is oriented to an object it is inhibited from returning to the
      same object following a short delay. This inhibition-of-return (IOR) effect is
      modulated by an edge discontinuity presented between cue and target--an effect
      referred to as structure-based modulation of IOR. Here we examined two
      alternative accounts for the structure-based modulation effect. On one account
      the modulation is caused by the presence of any intervening feature between cue
      and target. On another account the modulation is caused by edge-bounded (i.e.,
      closed) regions of space, on which space-based selection mechanisms operate. We
      presented cues and targets on unsegmented and internally or externally segmented
      rectangles to examine the two alternative accounts for the effect. Contrary to
      the predictions of the two alternative accounts, structure-based modulation of
      IOR was found with the internally but not with the externally segmented displays.
      This supports our hypothesis that object-based IOR arises from perceptually
      complete and internally structured object representations.

PMID- 16987778
TI  - The impact of path crossing on visuo-spatial serial memory: encoding or rehearsal
      effect?
AB  - The determinants of visuo-spatial serial memory have been the object of little
      research, despite early evidence that not all sequences are equally remembered.
      Recently, empirical evidence was reported indicating that the complexity of the
      path formed by the to-be-remembered locations impacted on recall performance,
      defined for example by the presence of crossings in the path formed by successive
      locations (Parmentier, Elford, & Maybery, 2005). In this study, we examined
      whether this effect reflects rehearsal or encoding processes. We examined the
      effect of a retention interval and spatial interference on the ordered recall of
      spatial sequences with and without path crossings. Path crossings decreased
      recall performance, as did a retention interval. In line with the encoding
      hypothesis, but in contrast with the rehearsal hypothesis, the effect of crossing
      was not affected by the retention interval nor by tapping. The possible nature of
      the impact of path crossing on encoding mechanisms is discussed.

PMID- 16987779
TI  - Scalar properties in animal timing: conformity and violations.
AB  - The article reviews data from animal subjects on a range of timing tasks
      (including fixed-interval and temporal differentiation schedules, stimulus
      timing, aversive conditioning, and Pavlovian methods) with respect to conformity
      to the two scalar properties of timing behaviour: mean accuracy and scalar
      (Weberian) variance. Systematic deviations were found in data from temporal
      differentiation schedules, timing of very short (<100 ms) or very long (>100 s)
      durations, effects of "task difficulty", and some special cases where circadian
      and interval timing seemed to interact, or where some specific durations seemed
      to be timed more precisely than others. Theoretical reconciliation of some of
      these deviations with underlying scalar timing can be achieved, but a number of
      problematical cases remain unexplained.

PMID- 16987780
TI  - Observational learning of instrumental discriminations in the rat: the role of
      demonstrator type.
AB  - In two experiments, observer rats saw a pretrained demonstrator rat of either the
      same or a different strain engaging in a discrimination task in which the
      presentation of a discriminative stimulus indicated whether performing a
      particular response (pulling a chain) would be reinforced. In both experiments an
      effect of demonstrator familiarity was found: Observers of a demonstrator from a
      different strain behaved in a manner that was consistent with the demonstrator
      whereas observers of a demonstrator from the same strain did not. These results
      suggest that an effect akin to latent inhibition operates in the social domain:
      Familiarity with the demonstrator retards the readiness with which observational
      learning proceeds.

PMID- 16987781
TI  - Attention to arrows: pointing to a new direction.
AB  - It was long believed that central arrows needed to be spatially predictive to
      produce a shift in spatial attention. Recent evidence indicates, however, that
      central spatially nonpredictive directional cues, like arrows, will trigger
      reflexive shifts in attention. We asked what this recent discovery means for past
      studies that used predictive directional cues such as arrows. Our findings
      indicate that predictive arrows produce attention effects that greatly exceed the
      individual or summed effects of reflexive orienting to nonpredictive arrows and
      volitional orienting to predictive numbers. This suggests that the especially
      large effect produced by predictive arrows reflects an interaction between
      reflexive and volitional orienting. Given the broad application of the predictive
      arrow cueing paradigm in both past and current research, the present data shed
      new light on a wide range of investigations, from psychophysical studies of basic
      attention to behavioural and neuroimaging studies of cognition and social
      development.

PMID- 16987782
TI  - Visual saliency and semantic incongruency influence eye movements when inspecting
      pictures.
AB  - Models of low-level saliency predict that when we first look at a photograph our
      first few eye movements should be made towards visually conspicuous objects. Two
      experiments investigated this prediction by recording eye fixations while viewers
      inspected pictures of room interiors that contained objects with known saliency
      characteristics. Highly salient objects did attract fixations earlier than less
      conspicuous objects, but only in a task requiring general encoding of the whole
      picture. When participants were required to detect the presence of a small
      target, then the visual saliency of nontarget objects did not influence
      fixations. These results support modifications of the model that take the
      cognitive override of saliency into account by allowing task demands to reduce
      the saliency weights of task-irrelevant objects. The pictures sometimes contained
      incongruent objects that were taken from other rooms. These objects were used to
      test the hypothesis that previous reports of the early fixation of congruent
      objects have not been consistent because the effect depends upon the visual
      conspicuity of the incongruent object. There was an effect of incongruency in
      both experiments, with earlier fixation of objects that violated the gist of the
      scene, but the effect was only apparent for inconspicuous objects, which argues
      against the hypothesis.

PMID- 16987783
TI  - Comparing distances in mental images constructed from visual experience or verbal
      descriptions: the impact of survey versus route perspective.
AB  - Mental images constructed after visual examination of a spatial configuration or
      after processing a verbal description of that configuration have been shown to
      share similar properties, in particular the capacity to preserve metric
      information contained in the configuration represented. In the present study, we
      investigated the properties of mental images constructed under learning
      conditions resulting from the combination of a visual or a verbal mode of
      acquisition and a survey or route perspective. Participants memorized a virtual
      environment (a garden containing six objects) under one of four learning
      conditions: (a) viewing a map of the garden (visual-survey); (b) viewing a video
      presentation of a journey along the path around the garden (visual-route); (c)
      listening to a verbal description of the map of the garden (verbal-survey); and
      (d) listening to a verbal description of the journey around the garden (verbal
      route). The participants were then invited to compare the distances separating
      objects in the garden mentally. Experiment 1, where the pairs of distances to be
      compared had a common starting point, revealed that the frequency of correct
      responses was higher, and response times were shorter when participants had
      learned about the environment visually rather than by a verbal description. The
      conditions involving a survey perspective resulted in a higher frequency of
      correct responses and shorter response times than those involving a route
      perspective. Lastly, a symbolic distance effect was obtained in the first three
      conditions, in that the greater the difference between the two distances being
      compared, the higher the frequency of correct responses, and the shorter the
      response times. Experiment 2, where the pairs of distances had different starting
      points, replicated these results, although longer response times revealed that
      the comparison process was more costly. Taken together, these findings support
      the view that mental spatial representations derived from different sources and
      adopting different perspectives contain genuine metric properties, except when
      the verbal modality and the route perspective are combined during learning.

PMID- 16987784
TI  - Dual-modality monitoring in a classification task: the effects of bilingualism
      and ageing.
AB  - Two experiments are reported in which monolingual and bilingual participants who
      were younger (Experiment 1) or older (Experiment 2) adults performed in a dual
      task classification paradigm. Visually (primary task) and auditorily (secondary
      task) presented stimuli were classified into two categories. The stimuli belonged
      to two domains, letters or numbers (LN) and animals or musical instruments (AM),
      and the two task modalities used stimuli from the same (related) or opposite
      (unrelated) domains. For both age groups, bilinguals were less disrupted than
      monolinguals in visual sorting in the LN domain, and relatedness affected
      performance only in the AM domain. The results indicate different processing
      demands for the two domains, with the simpler domain (LN) favouring bilinguals
      and the more semantically complex domain (AM) favouring related judgements for
      the two task modalities.

PMID- 16987785
TI  - Primacy of functional knowledge in semantic representations: the case of living
      and nonliving things.
AB  - In 3 experiments, participants decided whether sensory and functional features
      were true of living and nonliving concepts. In Experiments 1 and 2, concepts were
      presented twice: test phase followed study phase after either 3 min (Experiment
      1) or 3 s (Experiment 2). At test, concepts were paired with the same feature as
      that at study, or a different feature from either the same modality (within
      modality priming) or another modality (cross-modality priming). In both
      experiments functional decisions were faster than sensory decisions for living
      and nonliving concepts. Whilst no semantic priming occurred between study and
      test in Experiment 1, the shorter study-test interval of Experiment 2 did lead to
      test phase semantic priming. Here there was greater within- than cross-modality
      priming for sensory decisions, but equivalent within- and cross-modality priming
      for functional decisions owing to significantly greater facilitation of
      functional decisions from prior sensory decisions than vice versa. Experiment 3
      involved a single verification phase: For half the participants the feature name
      preceded the concept name, and for half the concept name preceded the feature
      name. The functional processing advantage persisted irrespective of presentation
      order. Results suggest that functional information is central to the
      representation of all concepts: Function is processed faster than sensory
      information and is activated obligatorily.

PMID- 16987786
TI  - Orthographic influences on phoneme deletion response times.
AB  - The aim of this paper is to provide further evidence that orthography plays a
      central role in phonemic awareness, by demonstrating an orthographic congruency
      effect in phoneme deletion. In four initial phoneme deletion experiments, adult
      participants produced the correct response more slowly with orthographically
      mismatched stimulus-response pairs (e.g., worth-earth) than with matched pairs
      (e.g., wage-age). This orthographic effect occurred with or without specific
      instructions to ignore spelling and when stimuli were presented with or without
      the to-be-deleted sound. In a final experiment, participants made more errors on
      complex than simple onset items, but there was no interaction with orthographic
      mismatch. The repeated observation of this robust orthographic effect suggests
      that participants are at least aware of orthography during phonemic awareness
      tasks, and it supports the view that phonemic awareness is directly subserved by
      orthography.

PMID- 16987787
TI  - Task selection and enriched environments: a functional upper extremity training
      program for stroke survivors.
AB  - Functional tasks using real-life objects in an enriched environment provide a
      multidimensional approach to treatment. Functional tasks are therapeutic for
      stroke survivors, because they require the simultaneous use of motor control,
      cognition, visual perception, sensation, and motor planning. Therapists utilizing
      functional tasks as treatment modalities must also be multidimensional in their
      implementation. This article provides a systematic approach to guide therapists
      in developing a functional upper extremity training program for stroke survivors.

PMID- 16987788
TI  - Visual deficits following stroke: maximizing participation in rehabilitation.
AB  - This article reviews the literature regarding the prevalence, etiology, and
      clinical symptoms of various visual deficits including those that are age related
      and those that are a result of neurological damage to the brain, such as in
      traumatic brain injury or stroke. It discusses treatment options provided by an
      occupational therapist, along with other members of the rehabilitation team, to
      educate the patient and family members regarding vision loss, to accommodate for
      visual loss, and to optimize independence with activities of daily living. This
      article also briefly reviews the literature and discusses possibilities for
      individuals who identify computer access and return to driving as goal areas.

PMID- 16987789
TI  - Computer access for people after stroke.
AB  - This article will focus on computer access options for people who have had a
      stroke. The role of the occupational therapist and assistive technology
      specialist in evaluation, prescription, and training will be addressed. Options
      related to physical, perceptual, or cognitive impairments (following a stroke) to
      allow for access to the computer or to increase efficiency will be discussed.
      Alternative hardware, software options, and modifications to the operating system
      will be described.

PMID- 16987790
TI  - Kinesio taping in stroke: improving functional use of the upper extremity in
      hemiplegia.
AB  - The purpose of this article is to present the Kinesio taping method used to
      improve the upper extremity function in the adult with hemiplegia. The article
      discusses various therapeutic methods used in the treatment of stroke patients to
      achieve a functional upper extremity. The only taping technique for various upper
      extremity conditions that has been described in the literature is the athletic
      taping technique. In this article, some interpretation is offered on proper
      assessment of the nonfunctional upper extremity, including the emphasis on
      postural alignment, trunk control, and scapula alignment. The Kinesio taping
      method in conjunction with other therapeutic interventions may facilitate or
      inhibit muscle function, support joint structure, reduce pain, and provide
      proprioceptive feedback to achieve and maintain preferred body alignment.
      Restoring trunk and scapula alignment after the stroke is critical in an
      effective treatment program for the upper extremity in hemiplegia.

PMID- 16987791
TI  - Examining barriers and supports to community living and participation after a
      stroke from a participatory action research approach.
AB  - This participatory action research study focused on identifying community
      participation goals, barriers, and supports/strategies in partnership with people
      who have experienced a stroke. Goals demonstrate that participation is more than
      activity performance in context; instead, it relates to "being a part of" the
      community and having access to participation opportunities and supports. Results
      of community site audits from the first 20 participants document environmental
      (physical, cognitive, social) and system level barriers, as well as effective
      strategies for promoting participation via environmental modification and systems
      level changes. A consumer-directed, Web-based tool for documenting participation
      barriers and sharing strategies is discussed.

PMID- 16987792
TI  - Evidence-based practice and setting basic standards for stroke rehabilitation in
      Canada.
AB  - It is a concern that the consistency of care in stroke rehabilitation appears to
      vary significantly among practice settings within Canada. Based upon an evidence
      based review of stroke rehabilitation, a group of physiatrists from across Canada
      agreed to some basic standards for stroke rehabilitation. The following standards
      were deemed to be critical to providing effective stroke rehabilitation care:
      early assessment and quick access to specialized interdisciplinary
      rehabilitation, appropriate intensity of therapies, availability of outpatient
      therapy, appropriate community supports, and careful attention to secondary
      prevention of stroke. Providing stroke rehabilitation care consistently within
      these standards remains a challenge, particularly given the potential initial
      costs, despite significant improvements in patient outcomes and quality of life.
      Nevertheless, these standards should be the expectation of stroke patients,
      essentially forming a stroke rehabilitation "bill of rights."

PMID- 16987793
TI  - Problems and associated feelings experienced by family caregivers of stroke
      survivors the second and third month postdischarge.
AB  - This study identified problems and associated feelings experienced by family
      caregivers of stroke survivors during the second and third month after discharge
      from a rehabilitation facility to home. Safety was the most frequent problem
      identified by family caregivers. Other problems were managing activities of daily
      living (ADLs) and cognitive, behavioral, and emotional changes by stroke
      survivors. About half of caregivers expressed more positive feelings toward
      managing these problems by week 8 and the majority expressed these feelings by
      week 12.

PMID- 16987794
TI  - Clinician perspectives on decision-making capacity after acquired brain injury.
AB  - Acquired brain injury frequently alters an individual's ability to make health
      care decisions based on a clear understanding of the situation and options. This
      exploratory study investigated the ways health care providers address issues of
      decisionmaking capacity (DMC) on a daily, functional basis. 33 clinicians
      providing rehabilitation services to persons with acquired brain injury
      participated in 1 of 5 semi-structured focus groups. All 33 participants,
      representing 8 different occupations, agreed that DMC determinations affected
      their practice every day. Participants underscored a multidimensional rather than
      a unitary definition of DMC, with an emphasis on fluctuating capacities due to
      the injury. Important concerns were for the safety of the person with brain
      injury, the health care provider, and community members. Other themes included
      rehabilitation team involvement, family context, and professional socialization.
      Clinical determinations of DMC are context dependent and are affected by the
      abilities of the individual and the substance and consequences of the decision
      being made and include the concepts of regaining trust and reclaiming capacity.

PMID- 16987795
TI  - Loss and hope: strategies for coping with aphasia.
AB  - Speaking from almost 30 years of experience living with aphasia, the author
      offers suggestions for health care professionals who relate to persons with this
      disorder. Persons with aphasia should be involved in meaningful activities, learn
      to accept limitations, build trusting relationships, strengthen social support,
      and find tools that facilitate communication.

PMID- 16987796
TI  - Observation of a rare hemoglobin variant [Hb Lulu island, beta107(G9)Gly-->Asp,
      GGC-->GAC] co-inherited with a beta+-thalassemia mutation [IVS-I-110 (G-->A)] or
      in the heterozygous state in a Greek-Albanian family.
AB  - We report clinical, hematological, biochemical, functional and molecular studies
      carried out on two first cousins from a Greek-Albanian family who have clinical
      and hematological findings consistent with the diagnosis of thalassemia
      intermedia. DNA studies determined that they had co-inherited a common
      Mediterranean beta-thalassemia (thal) mutation, IVS-I-110 (G-->A), in trans to a
      beta-globin gene mutation at codon 107 (GGC-->GAC), predicted to give rise to a
      rare unstable beta chain variant Hb Lulu Island or beta107(G9)Gly-->Asp.

PMID- 16987797
TI  - Accurate measurements of fetal hemoglobin for neonates with different gestational
      ages.
AB  - The purposes of this study were to examine the accuracy of fetal hemoglobin (Hb
      F, alpha2gamma2) as quickly measured by a hemoximeter but verified by high
      performance liquid chromatography [HPLC, including Hb F total (Hb Ft), acetylated
      Hb F (Hb F1), and non acetylated Hb F ( Hb F*)], and to predict the Hb F levels
      for different gestational weeks of neonates. Thirty-nine neonates of
      predominantly Hispanic and African American ethnicity, with gestational ages
      ranging from 25 to 38 weeks, were investigated. Analyses were performed on 163
      blood samples that were pure neonates' blood before the transfusion of any adult
      blood. Two neonates had increased Hb C [beta6(A3)Glu-->Lys, GAC-->AAG] levels
      (1.67-2.79%) and one neonate whose mother drank alcohol during pregnancy, had
      elevated Hb A2 levels (0.12-0.14%). After excluding these data points, the mean
      Hb F were overestimated by hemoximeter, 118.4 +/- 8.77% vs. 92.6 +/- 2.77% by
      HPLC (mean difference: 25.8 +/- 7.71%, p = <0.001). Mean Hb F1 was 10.5 +/-
      2.28%. Hb F levels decreased as gestational age increased (p <0.001 for Hb Ft and
      Hb F*; p = <0.05 for Hb F1). A multivariate regression model for Hb F prediction
      was established with the best R2. The gestational age and post birth hours in the
      prediction of Hb Ft was included when Hb F could be determined at the clinical
      settings. Future studies may be needed to account for Hb F1 when measuring Hb F
      levels to assess oxygenation status in (pre term) neonates.

PMID- 16987798
TI  - Detection of two rare beta-thalassemia alleles found in the Tunisian population:
      codon 47 (+A) and codons 106/107 (+G).
AB  - We here present the first report of the detection of two rare beta0-thalassemia
      (thal) mutations in the Tunisian population: codon 47 (+A) and codons 106/107
      (+G). To the best of our knowledge this is the second report of the codon 47 (+A)
      mutation, the first being identified in a Surinamese subject. The codons 106/107
      (+G) mutation was first described in American Blacks, subsequently in Egyptians
      and Palestinians, and now in Tunisians. These mutations were detected by
      denaturing gradient gel electrophoresis (DGGE) screening followed by automated
      nucleotide sequencing. The former was found in two related beta-thal major
      patients in the homozygous state, while the latter was identified in a homozygous
      state in a transfusion-dependent beta-thal subject and in a sickle cell beta-thal
      patient. Both mutations are in linkage disequilibrium with haplotype V and
      sequence framework 2. Given the known wide spectrum of beta-thal alleles in the
      Tunisian population, the present report further confirms such heterogeneity. The
      knowledge of an updated spectrum of beta-thal alleles in Tunisia must allow the
      implementation of a more efficient screening strategy for genetic counseling and
      prenatal diagnosis.

PMID- 16987799
TI  - Association of the methylenetetrahydrofolate reductase A1298C but not the C677T
      single nucleotide polymorphism with sickle cell disease in Bahrain.
AB  - The association of methylenetetrahydrofolate reductase (MTHFR) gene mutations,
      C677T and A1298C, together with changes in homocysteine (Hcy) levels was
      investigated in 106 sickle cell disease patients and 156 healthy controls from
      Bahrain. The mutation analysis was done by restriction fragment length
      polymorphism-polymerase chain reaction (RFLP-PCR). While the frequencies of the
      mutant alleles C677T and A1298C were comparable between patients and controls,
      the frequency of the A1298C (C/C) (p = 0.03) but not C677T (T/T) (p = 0.67)
      genotype, and of the 677T/1298C haplotype were significantly higher in the
      patients (p = 0.05). Homocysteine levels were normal in all subjects. This
      suggests that the A1298C, but not C677T, mutation is associated with the genotype
      of sickle cell disease.

PMID- 16987800
TI  - Delta-thalassemia in Cyprus.
AB  - To help clarify the hematological picture of patients who may be positive for
      beta- and delta-globin gene mutations, the following study was carried out. Our
      aim was to identify the delta-globin gene mutations found in the Greek Cypriot
      population, their frequencies and the Hb A2 values associated with them. Seventy
      four samples were selected from a random sample of 5,030 individuals, and the
      database of the Molecular Genetics Thalassaemia Department containing diagnostic
      analyses data was also mined for relevant information. Four novel for Cyprus
      delta-globin gene mutations: -30 (T-->C), Hb A2-Wrens [delta98(FG5)Val-->Met, GTG
      ->ATG], IVS-I-2 (T-->C) and Hb A2-Yokoshima [delta25(B7)Gly-->Asp (GGT-->GAT)]
      were identified. Hb A2-Yialousa [delta27(B9)Ala-->Ser, GCC-->TCC], Hb A2
      Yokoshima, Hb A2-Troodos [delta116(G18)Arg-->Cys, CGC-->TGC], Hb A2-Pelendri
      [delta141(H19)Leu-->Pro, CTG-->CCG], codon 4 [delta4(A1)Thr-->Ile], codon 59 (
      A), Hb A2-Wrens, IVS-II-897 (A-->G), IVS-I-2, -55 (T-->C) and -30 bring the total
      to 11 delta-globin alleles found in the Greek Cypriot population. Hb A2-Yialousa
      is the most common mutation followed by codon 4, with frequencies of 60.7 and
      17.8%, respectively.Hb A2 levels above 1.9% have been found to indicate a
      significantly reduced possibility for the presence of a delta-globin gene
      mutation in this population. For Hb A2 levels of 1.7 and 1.8% the possibility of
      a delta-globin gene mutation rises to 90.9% and reaches 100% for lower Hb A2
      levels. The frequency of all the mutant delta-globin chromosomes in the sample is
      0.0067 and the carrier frequency is 1.26%.

PMID- 16987802
TI  - A newly identified deletion of 970 bp at the alpha-globin locus that removes the
      promoter region of the alpha1 gene.
AB  - The most common causes of alpha-thalassemia (thal) are deletions that remove a
      part, or one or both of the functional alpha-globin genes. These deletions cause
      diminished expression of the alpha-globin protein, which may result in relatively
      low hemoglobin (Hb) and/or mean corpuscular volume (MCV) values. We here report
      the identification of a 970 bp deletion in the alpha1-globin gene that
      encompasses the entire promoter region of the alpha1-globin gene and 26 bp
      encoding the 5' end of the mRNA. Thus, the affected alpha1-globin gene is prone
      to be nonfunctional. We therefore nominated the newly identified deletion allele
      alpha-alphaDelta970. The MCV values of four related carriers of the alpha
      alphaDelta970 allele were slightly lowered, consistent with the presence of three
      functional alpha-globin genes.

PMID- 16987801
TI  - The prevalence and molecular basis of hemoglobinopathies in Cambodia.
AB  - Blood counts, hemoglobin (Hb) high performance liquid chromatography (HPLC), and
      DNA analyses were performed on 260 children, aged 5 months to 16 years, at Siem
      Reap to assess the prevalence of thalassemia and other hemoglobinopathies in
      regional Cambodia. Hemoglobinopathies were present in 134 children (51.5%) with
      20 abnormal genotypes identified. alpha-Thalassemia (thal) (35.4%) was the most
      prevalent disorder and the -alpha3.7 gene deletion was the most common alpha
      globin gene abnormality. The - -SEA deletion and nondeletional forms of alpha
      thal, Hb Constant Spring [Hb CS, alpha142, Term-->Gln, TAA-->CAA (alpha2)], Hb
      Pakse [alpha142, Term-->Tyr, TAA-->TAT (alpha2)] and triplicated alpha genes,
      were also present but at low frequencies. Hb E [beta26(B8)Glu-->Lys, GAG-->AAG]
      (28.8%) was the most common beta-globin gene abnormality, whilst beta-thal was
      only detected in two children (0.8% of cases). Although hemoglobinopathies were
      common, the majority of abnormalities detected (heterozygous -alpha3.7 and Hb E)
      were not clinically significant. On the basis of these findings, and with the
      majority of abnormalities being mild, it seems improbable that thalassemia
      represents a major health burden in this region of Cambodia.

PMID- 16987803
TI  - Molecular characterization of beta-thalassemia in the Dohuk region of Iraq.
AB  - beta-Thalassemia (thal) is an important health problem in the Dohuk region of
      northern Iraq because of its high carrier rate and the frequency of
      consanguineous marriages. Thus, the need to establish an effective preventative
      program is paramount. As part of this effort, we initiated this study to
      determine the molecular basis of this disorder in the region. For the latter
      purpose, either parent of 104 registered beta-thal major/intermedia patients had
      their full blood counts, hemoglobin (Hb) electrophoresis, Hb A2 and Hb F
      quantitation performed. Their DNA was extracted, amplified and reverse hybridized
      to specific oligonucleotide probes to detect 20 beta-thal mutations. The testing
      detected 12 beta-thalassemic mutations. The eight most frequent were: IVS-II-1 (G
      ->A), codon 44 (-C), codon 5 (-CT), IVS-I-1 (G-->A), codon 39 (C-->T), IVS-I-6 (T
      ->C), codons 8/9 (+G) and IVS-I-5 (G-->C). These mutations accounted for 81.7% of
      the thalassemic defects in the studied individuals. The less frequent mutations
      were: codon 8 (-AA), IVS-I-110 (G-->A), codon 30 (G-->C) and codon 22 (-7 bp),
      and the beta-thalassemic defects remained uncharacterized in 11.5% of cases. This
      is the first study of beta-thal mutations from Iraq, and shows a frequency of
      thalassemic defects different from those reported in surrounding countries. It
      provides a foundation for prenatal genetic testing that will be part of a
      thalassemia prevention program in the Dohuk region.

PMID- 16987804
TI  - The JAK2 V617F mutation is absent in patients with erythrocytosis due to high
      oxygen affinity hemoglobin variants.
AB  - High oxygen affinity hemoglobin (Hb) variants are an important and well
      characterized cause of secondary erythrocytosis. We tested 22 patients with high
      oxygen affinity beta chain variants for the presence of the JAK2 V617F mutation
      that has been reported in chronic myeloproliferative disorders, particularly
      polycythemia vera. All specimens showed the absence of this mutation. This
      observation contributes to the overall clinical specificity of the JAK2 V617F
      mutation.

PMID- 16987805
TI  - The ACT domain: a small molecule binding domain and its role as a common
      regulatory element.

PMID- 16987806
TI  - The VASP-Spred-Sprouty domain puzzle.
AB  - Sprouty-related proteins with an EVH1 domain (Spreds) belong to a new protein
      family harboring a conserved N-terminal EVH1 domain, which is related to the VASP
      (vasodilator-stimulated phosphoprotein) EVH1 domain (Enabled/VASP homology 1
      domain) and a C-terminal Sprouty-related domain, typical for Sprouty proteins.
      Spreds were, like Sproutys, initially discovered as inhibitors of the Ras/MAPK
      pathway, and the SPR (Sprouty-related) domains of both protein families seem to
      be very important for many protein interactions and cellular processes. VASP was
      initially characterized as a proline-rich substrate of protein kinases A and G in
      human platelets and later shown to be a scaffold protein, regulating both signal
      transduction pathways and the actin filament system. The VASP-EVH1 domain is
      known to bind specifically to a FP(4) binding motif, which is, for example,
      present in the focal adhesion proteins vinculin and zyxin. In this review we give
      a structural and functional overview on these three protein families and ask
      whether nature plays a modular protein domain puzzle with stable exchangeable
      elements or if these closely related domains have various functions when pasted
      in a different protein context.

PMID- 16987807
TI  - The ins and outs of MYC regulation by posttranslational mechanisms.
AB  - The proteins of the MYC family are key regulators of cell behavior. MYC,
      originally identified as an oncoprotein, affects growth, proliferation,
      differentiation, and apoptosis of cells through its ability to regulate a
      significant number of genes. In addition MYC governs events associated with tumor
      progression, including genetic stability, migration, and angiogenesis. The
      pleiotropic activities attributed to MYC and their balanced control requires that
      the expression and function of MYC is tightly controlled. Indeed many different
      pathways and factors have been identified that impinge on MYC gene expression and
      protein function. In particular the protein is subject to different
      posttranslational modifications, including phosphorylation, ubiquitinylation, and
      acetylation. Here we discuss the latest developments regarding these
      modifications that control various aspects of MYC function, including its
      stability, the interaction with partner proteins, and the transcriptional
      potential.

PMID- 16987808
TI  - Investigating the Qn site of the cytochrome bc1 complex in Saccharomyces
      cerevisiae with mutants resistant to ilicicolin H, a novel Qn site inhibitor.
AB  - The cytochrome bc1 complex resides in the inner membrane of mitochondria and
      transfers electrons from ubiquinol to cytochrome c. This electron transfer is
      coupled to the translocation of protons across the membrane by the protonmotive Q
      cycle mechanism. This mechanism topographically separates reduction of quinone
      and reoxidation of quinol at sites on opposite sites of the membrane, referred to
      as center N (Qn site) and center P (Qp site), respectively. Both are located on
      cytochrome b, a transmembrane protein of the bc1 complex that is encoded on the
      mitochondrial genome. To better understand the parameters that affect ligand
      binding at the Qn site, we applied the Qn site inhibitor ilicicolin H to select
      for mutations conferring resistance in Saccharomyces cerevisiae. The screen
      resulted in seven different single amino acid substitutions in cytochrome b
      rendering the yeast resistant to the inhibitor. Six of the seven mutations have
      not been previously linked to inhibitor resistance. Ubiquinol-cytochrome c
      reductase activities of mitochondrial membranes isolated from the mutants
      confirmed that the differences in sensitivity toward ilicicolin H originated in
      the cytochrome bc1 complex. Comparative in vivo studies using the known Qn site
      inhibitors antimycin and funiculosin showed little cross-resistance, indicating
      different modes of binding of these inhibitors at center N of the bc1 complex.

PMID- 16987809
TI  - Blood group antigen recognition by a Streptococcus pneumoniae virulence factor.
AB  - The Streptococcus pneumoniae fucose utilization operon includes a gene encoding a
      virulence factor that belongs to family 98 in the glycoside hydrolase
      classification. This protein contains a C-terminal triplet of fucose binding
      modules that have significant amino acid sequence identity with the Anguilla
      anguilla fucolectin. Functional studies of these fucose binding modules reveal
      binding to fucosylated oligosaccharides and suggest the importance of multivalent
      binding. The high resolution crystal structures of ligand bound forms of one
      fucose binding module uncovers the molecular basis of fucose, ABH blood group
      antigen, and Lewisy antigen binding. These studies are extended by fluorescence
      microscopy to show specific binding to mouse lung tissue. These modules define a
      new family of carbohydrate binding modules now classified as family 47.

PMID- 16987810
TI  - The role of CKIP-1 in cell morphology depends on its interaction with actin
      capping protein.
AB  - CKIP-1 is a pleckstrin homology domain-containing protein that induces
      alterations of the actin cytoskeleton and cell morphology when expressed in human
      osteosarcoma cells. CKIP-1 interacts with the heterodimeric actin-capping protein
      in cells, so we postulated that this interaction was responsible for the observed
      cytoskeletal and morphological effects of CKIP-1. To test this postulate, we used
      peptide "walking arrays" and alignments of CKIP-1 with CARMIL, another CP-binding
      protein, to identify Arg-155 and Arg-157 of CKIP-1 as residues potentially
      required for its interactions with CP. CKIP-1 mutants harboring Arg-155 and Arg
      157 substitutions exhibited greatly decreased CP binding, while retaining wild
      type localization, the ability to interact with protein kinase CK2, and self
      association. To examine the phenotype associated with expression of these
      mutants, we generated tetracycline-inducible human osteosarcoma cells lines
      expressing R155E,R157E mutants of CKIP-1. Examination of these cell lines reveals
      that CKIP-1 R155E,R157E did not induce the distinct changes in cell morphology
      and the actin cytoskeleton that are characteristic of wild-type CKIP-1
      demonstrating that the interaction between CKIP-1 and CP is required for these
      cellular effects.

PMID- 16987811
TI  - Dietary flavonoids attenuate tumor necrosis factor alpha-induced adhesion
      molecule expression in human aortic endothelial cells. Structure-function
      relationships and activity after first pass metabolism.
AB  - Flavonoids have been suggested to exert human health benefits by anti-oxidant and
      anti-inflammatory mechanisms. In this study, we investigated whether and by what
      mechanisms dietary flavonoids inhibit expression of cellular adhesion molecules,
      which is relevant to inflammation and atherosclerosis. We found that the capacity
      of flavonoids to inhibit tumor necrosis factor alpha-induced adhesion molecule
      expression in human aortic endothelial cells was dependent on specific structural
      features of the flavonoids. The 5,7-dihydroxyl substitution of a flavonoid A-ring
      and 2,3-double bond and 4-keto group of the C-ring were the main structural
      requirements for inhibition of adhesion molecule expression. In striking
      contrast, hydroxyl substitutions of the B- and C-rings but not the A-ring were
      essential for antioxidant activity. Hence, only hydroxyl flavones, such as
      apigenin and chrysin, and flavonols, such as galangin, kaempferol, and quercetin,
      were able to inhibit endothelial adhesion molecule expression, whereas flavone,
      chromone, the flavanone, naringenin, and the flavanol, (-)-epicatechin, were
      ineffectual. At low concentrations, the active flavonoids significantly
      attenuated expression of E-selectin and intercellular adhesion molecule 1 but not
      vascular cell adhesion molecule 1. In addition, exposure of apigenin and
      kaempferol to cultured hepatocytes, mimicking first pass metabolism, greatly
      diminished the inhibitory effect of flavonoids on endothelial intercellular
      adhesion molecule 1 expression. We conclude that the effect of dietary flavonoids
      on endothelial adhesion molecule expression depends on their molecular structure,
      concentration, and metabolic transformation but not their antioxidant activity.

PMID- 16987812
TI  - Inhibition of fructose-1,6-bisphosphatase by aminoimidazole carboxamide ribotide
      prevents growth of Salmonella enterica purH mutants on glycerol.
AB  - The enzyme fructose-1,6-bisphosphatase (FBP) is key regulatory point in
      gluconeogenesis. Mutants of Salmonella enterica lacking purH accumulate 5-amino-4
      imidazole carboxamide ribotide (AICAR) and are unable to utilize glycerol as sole
      carbon and energy sources. The work described here demonstrates this lack of
      growth is due to inhibition of FBP by AICAR. Mutant alleles of fbp that restore
      growth on glycerol encode proteins resistant to inhibition by AICAR and the
      allosteric regulator AMP. This is the first report of biochemical
      characterization of substitutions causing AMP resistance in a bacterial FBP.
      Inhibition of FBP activity by AICAR occurs at physiologically relevant
      concentrations and may represent a form of regulation of gluconeogenic flux in
      Salmonella enterica.

PMID- 16987813
TI  - Transglutaminase 2 mediates polymer formation of I-kappaBalpha through C-terminal
      glutamine cluster.
AB  - Recently we reported that transglutaminase 2 (TGase 2) activates nuclear factor
      kappaB (NF-kappaB) independently of I-kappaB kinase (IKK) activation, by inducing
      cross-linking and protein polymer formation of inhibitor of nuclear factor
      kappaBalpha (I-kappaBalpha). TGase 2 catalyzes covalent isopeptide bond formation
      between the peptide bound-glutamine and the lysine residues. Using matrix
      assisted laser desorption ionization time-of-flight mass spectra analysis of I
      kappaBalpha polymers cross-linked by TGase 2, as well as synthetic peptides in an
      in vitro competition assay, we identified a glutamine cluster at the C terminus
      of I-kappaBalpha (amino acids 266-268) that appeared to play a key role in the
      formation of I-kappaBalpha polymers. Although there appeared to be no requirement
      for specific lysine residues, we found a considerably higher preference for the
      use of lysine residues at positions 21, 22, and 177 in TGase 2-mediated cross
      linking of I-kappaBalpha. We demonstrated that synthetic peptides encompassing
      the glutamine cluster at amino acid positions 266-268 reversed I-kappaBalpha
      polymerization in vitro. Furthermore, the depletion of free I-kappaBalpha in
      EcR/TG cells was completely rescued in vivo by transfection of mutant I
      kappaBalphas in glutamine sites (Q266G, Q267G, and Q313G) as well as in a lysine
      site (K177G). These findings provide additional clues into the mechanism by which
      TGase 2 contributes to the inflammatory process via activation of NF-kappaB.

PMID- 16987814
TI  - Neural cell adhesion molecule-associated polysialic acid inhibits NR2B-containing
      N-methyl-D-aspartate receptors and prevents glutamate-induced cell death.
AB  - The neural cell adhesion molecule (NCAM) and its associated glycan polysialic
      acid play important roles in the development of the nervous system and N-methyl-D
      aspartate(NMDA)receptor-dependent synaptic plasticity in the adult. Here, we
      investigated the influence of polysialic acid on NMDA receptor activity. We found
      that glutamate-elicited NMDA receptor currents in cultured hippocampal neurons
      were reduced by approximately 30% with the application of polysialic acid or
      polysialylated NCAM but not by the sialic acid monomer, chondroitin sulfate, or
      non-polysialylated NCAM. Polysialic acid inhibited NMDA receptor currents
      elicited by 3 microm glutamate but not by 30 microm glutamate, suggesting that
      polysialic acid acts as a competitive antagonist, possibly at the glutamate
      binding site. The polysialic acid induced effects were mimicked and fully
      occluded by the NR2B subunit specific antagonist, ifenprodil. Recordings from
      single synaptosomal NMDA receptors reconstituted in lipid bilayers revealed that
      polysialic acid reduced open probability but not the conductance of NR2B
      containing NMDA receptors in a polysialic acid and glutamate concentration
      dependent manner. The activity of single NR2B-lacking synaptosomal NMDA receptors
      was not affected by polysialic acid. Application of polysialic acid to
      hippocampal cultures reduced excitotoxic cell death induced by low micromolar
      concentration of glutamate via activation of NR2B-containing NMDA receptors,
      whereas enzymatic removal of polysialic acid resulted in increased cell death
      that occluded glutamate-induced excitotoxicity. These observations indicate that
      the cell adhesion molecule-associated glycan polysialic acid is able to prevent
      excitotoxicity via inhibition of NR2B subunit-containing NMDA receptors.

PMID- 16987815
TI  - A membrane-targeted BID BCL-2 homology 3 peptide is sufficient for high potency
      activation of BAX in vitro.
AB  - The multidomain pro-apoptotic proteins BAX and BAK constitute an essential
      gateway to mitochondrial dysfunction and programmed cell death. Among the "BCL-2
      homology (BH) 3-only" members of pro-apoptotic proteins, truncated BID (tBID) has
      been implicated in direct BAX activation, although an explicit molecular
      mechanism remains elusive. We find that BID BH3 peptide alone at submicromolar
      concentrations cannot activate BAX or complement BID BH3 mutant-tBID in
      mitochondrial and liposomal release assays. Because tBID contains structurally
      defined membrane association domains, we investigated whether membrane targeting
      of BID BH3 peptide would be sufficient to restore its pro-apoptotic activity. We
      developed a Ni(2+)-nitrilotriacetic acid liposomal assay system that efficiently
      conjugates histidine-tagged peptides to a simulated outer mitochondrial membrane
      surface. Strikingly, nanomolar concentrations of a synthetic BID BH3 peptide that
      is chemically tethered to the liposomal membrane activated BAX almost as
      efficiently as tBID itself. These results highlight the importance of membrane
      targeting of the BID BH3 domain in tBID-mediated BAX activation and support a
      model in which tBID engages BAX to trigger its pro-apoptotic activity.

PMID- 16987816
TI  - Insoluble aggregates and protease-resistant conformers of prion protein in
      uninfected human brains.
AB  - Aggregated prion protein (PrPSc), which is detergent-insoluble and partially
      proteinase K (PK)-resistant, constitutes the major component of infectious prions
      that cause a group of transmissible spongiform encephalopathies in animals and
      humans. PrPSc derives from a detergent-soluble and PK-sensitive cellular prion
      protein (PrPC) through an alpha-helix to beta-sheet transition. This transition
      confers on the PrPSc molecule unique physicochemical and biological properties,
      including insolubility in nondenaturing detergents, an enhanced tendency to form
      aggregates, resistance to PK digestion, and infectivity, which together are
      regarded as the basis for distinguishing PrPSc from PrPC. Here we demonstrate,
      using sedimentation and size exclusion chromatography, that small amounts of
      detergent-insoluble PrP aggregates are present in uninfected human brains.
      Moreover, PK-resistant PrP core fragments are detectable following PK treatment.
      This is the first study that provides experimental evidence supporting the
      hypothesis that there might be silent prions lying dormant in normal human
      brains.

PMID- 16987817
TI  - Temperature-sensitive eIF5A mutant accumulates transcripts targeted to the
      nonsense-mediated decay pathway.
AB  - The highly conserved protein eIF5A found in Archaea and all eukaryotes uniquely
      contains the posttranslationally formed amino acid hypusine. Despite being
      essential the functions of this protein and its modification remain unclear. To
      gain more insight into these functions temperature-sensitive mutants of the human
      EIF5A1 were characterized in the yeast Saccharomyces cerevisiae. Expression of
      the point mutated form V81G in a DeltaeIF5A strain of yeast led to a strongly
      temperature-sensitive phenotype and to a significantly reduced protein level at
      restrictive temperature. The mutant showed accumulation of a subset of mRNAs that
      was also observed in nonsense-mediated decay (NMD)-deficient yeast strains. After
      short incubation at restrictive temperature the mutant exhibited increased half
      lives of the intron containing CYH2 pre-mRNA and mature transcripts of NMD
      dependent genes. Reduced telomere silencing and shortening was detected in the
      V81G mutant further supporting similarities to NMD-deficient strains. Our data
      suggest that eIF5A mediates important cellular processes like cell viability and
      senescence through its effects on the stability of certain mRNAs.

PMID- 16987818
TI  - The role of a novel p97/valosin-containing protein-interacting motif of gp78 in
      endoplasmic reticulum-associated degradation.
AB  - Improperly folded proteins in the endoplasmic reticulum (ER) are eliminated via
      ER-associated degradation, a process that dislocates misfolded proteins from the
      ER membrane into the cytosol, where they undergo proteasomal degradation.
      Dislocation requires a subclass of ubiquitin ligases that includes gp78 in
      addition to the AAA ATPase p97/VCP and its cofactor, the Ufd1-Npl4 dimer. We have
      previously reported that gp78 interacts directly with p97/VCP. Here, we identify
      a novel p97/VCP-interacting motif (VIM) within gp78 that mediates this
      interaction. We demonstrate that the VIM of gp78 recruits p97/VCP to the ER, but
      has no effect on Ufd1 localization. We also show that gp78 VIM interacts with the
      ND1 domain of p97/VCP that was shown previously to be the binding site for Ufd1.
      To evaluate the role of Ufd1 in gp78-p97/VCP-mediated degradation of CD3delta, a
      known substrate of gp78, RNA interference was used to silence the expression of
      Ufd1 and p97/VCP. Inhibition of p97/VCP, but not Ufd1, stabilized CD3delta in
      cells that overexpress gp78. However, both p97/VCP and Ufd1 appear to be required
      for CD3delta degradation in cells expressing physiological levels of gp78. These
      results raise the possibility that Ufd1 and gp78 may bind p97/VCP in a mutually
      exclusive manner and suggest that gp78 might act in a Ufd1-independent
      degradation pathway for misfolded ER proteins, which operates in parallel with
      the previously established p97/VCP-Ufd1-Npl4-mediated mechanism.

PMID- 16987819
TI  - A highly specific mechanism of histone H3-K4 recognition by histone demethylase
      LSD1.
AB  - Human lysine-specific demethylase (LSD1) is a chromatin-modifying enzyme that
      specifically removes methyl groups from mono- and dimethylated Lys4 of histone H3
      (H3-K4). We used a combination of in vivo and in vitro experiments to
      characterize the substrate specificity and recognition by LSD1. Biochemical
      assays on histone peptides show that essentially all epigenetic modifications on
      the 21 N-terminal amino acids of histone H3 cause a significant reduction in
      enzymatic activity. Replacement of Lys4 with Arg greatly enhances binding
      affinity, and a histone peptide incorporating this mutation has a strong
      inhibitory power. Conversely, a peptide bearing a trimethylated Lys4 is only a
      weak inhibitor of the enzyme. Rapid kinetics measurements evidence that the
      enzyme is efficiently reoxidized by molecular oxygen with a second-order rate
      constant of 9.6x10(3) M-1 s-1, and that the presence of the reaction product does
      not greatly influence the rate of flavin reoxidation. In vivo experiments provide
      a correlation between the in vitro inhibitory properties of the tested peptides
      and their ability of affecting endogenous LSD1 activity. Our results show that
      epigenetic modifications on histone H3 need to be removed before Lys4
      demethylation can efficiently occur. The complex formed by LSD1 with histone
      deacetylases 1/2 may function as a "double-blade razor" that first eliminates the
      acetyl groups from acetylated Lys residues and then removes the methyl group from
      Lys4. We suggest that after H3-K4 demethylation, LSD1 recruits the forthcoming
      chromatin remodelers leading to the introduction of gene repression marks.

PMID- 16987820
TI  - Skipping of Exon 1 in the KCNQ1 gene causes Jervell and Lange-Nielsen syndrome.
AB  - The Jervell and Lange-Nielsen syndrome (JLNS) is a rare autosomal recessive form
      of the long QT syndrome linked with a profound hearing loss caused by mutations
      affecting both alleles of either the KCNQ1 or the KCNE1 gene. We carried out a
      mutant screening of the KCNQ1 and KCNE1 genes in a clinical diagnosed German
      family with JLNS. Family members were examined by single strand conformation
      polymorphism analysis and PCR and amplified products were characterized by DNA
      sequence analysis. We identified a splice donor mutation of exon 1 in the KCNQ1
      gene (G477+1A). Analysis of lymphocyte RNA by RT-PCR revealed that two
      symptomatic patients, homozygous for the mutant allele, exclusively produce KCNQ1
      transcripts lacking exon 1 leading to a frameshift that introduced a premature
      termination codon at exon 4. Mutant subunits, functionally characterized in
      Xenpous oocytes, were unable to form homomeric channels but strongly reduced IKs
      (slowly activating delayed rectifier potassium current) in vitro (mutant isoforms
      1 and 2 by 62 and 86%, respectively), a fact supposed to lead to severely
      affected heterozygous individuals. However, individuals heterozygous for the
      mutant allele exhibit an asymptomatic cardiac phenotype. Thus, the observed
      dominant-negative effect of mutant subunits in vitro is absent in vivo leaving
      heterozygous individuals unaffected. These data suggest mechanisms that prevent
      production of truncated KCNQ1 channel subunits in cardiomyocytes of individuals
      heterozygous for the mutant allele.

PMID- 16987821
TI  - Novel aspects in the epidemiology, pathophysiology and treatment of connective
      tissue diseases. Introduction.

PMID- 16987822
TI  - Pulmonary arterial hypertension (PAH) in connective tissue diseases.
AB  - Pulmonary arterial hypertension (PAH) is characterized by progressive
      obliteration of the small pulmonary vascular bed as a result of vascular
      proliferation and remodelling of the vessel wall leading to permanently increased
      pulmonary vascular resistance and elevated pulmonary artery pressures, which
      result in right heart failure and premature death. Pathologic processes behind
      the complex vascular changes associated with PAH include
      vasoconstrictor/vasodilator imbalance, thrombosis, misguided angiogenesis and
      inflammation. Besides idiopathic PAH, it can also occur in association with
      portal hypertension, HIV infection, congenital cardiac left-to-right shunts and
      connective tissue diseases (CTD). Unfortunately, despite recent major
      improvements in PAH treatment, no current therapy can yet cure this devastating
      condition. This review will briefly highlight epidemiology, pathogenesis, and
      diagnostic and treatment options known so far for PAH occurring in connection
      with CTD.

PMID- 16987823
TI  - Pathophysiology of cutaneous lupus erythematosus--novel aspects.
AB  - The pathophysiology of cutaneous lupus erythematosus (CLE) has been investigated
      in numerous studies demonstrating that the combination of specific cellular and
      molecular events is leading to inflammation and tissue damage in this disease.
      However, a complete understanding of the diverse pathophysiological mechanisms
      and interactions does not exist. Various environmental factors influence the
      clinical expression of CLE and a striking relationship has emerged between
      sunlight exposure and the various subtypes of this disease. In the past years,
      photoprovocation tests with different ultraviolet (UV) wavelengths have been
      approved to be an optimal way to evaluate photosensitivity in patients with CLE.
      Furthermore, research on the pathogenetic mechanisms of UV-induced skin lesions
      has become an increasingly dynamic field and several new aspects of this disease
      could be identified. In this review, the impact of UV exposure that contributes
      to the manifestations of CLE is discussed and recently reported mechanisms in the
      pathophysiology of this disease are considered including the clearance of
      apoptotic cells, expression of inducible nitric oxide synthase, function of
      CD4(+)CD25(+) regulatory T cells, and the role of chemokines for lymphocyte
      recruitment. Elucidation of the relevant factors might lead to future development
      of effective strategies to prevent abnormal reactivity in patients with CLE.

PMID- 16987824
TI  - The role of nitric oxide.
AB  - When studying the impact of endothelins (ETs) on physiology and pathophysiology,
      this needs to be done in the context of nitric oxide (NO) synthesis and action,
      since these two are closely intertwined in their action. Here, we will review the
      work demonstrating the crosstalk between endothelin-1 (ET-1) and NO, and the
      recent developments regarding the role of these two mediators in inflammatory
      processes. Moreover, we will discuss the role of NO in pro-inflammatory diseases
      and the potential mechanisms of the anti-inflammatory activity of ET receptor
      antagonism.

PMID- 16987826
TI  - Immunological basis of systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a disease of unknown aetiology characterized by
      excessive and often progressive fibrosis in skin and multiple internal organs, an
      aberrant immune activation marked by multiple humoral and cellular immunological
      abnormalities and pronounced alterations in the microvasculature. The
      pathogenesis of SSc is complex and, although progress in the understanding of the
      multiple processes underlying SSc has been made in recent years, no single
      unifying hypothesis explaining all aspects of this disease exists. Recent studies
      have suggested that the activation of the immune system is a key stimulus to
      vascular abnormalities and fibrosis. Once T-cells are activated, they infiltrate
      the skin lesions early, and produce the profibrotic cytokine IL-4. They are also
      required for autoantibody production. B-cells may contribute to fibrosis, as
      deficiency of CD19, a B-cell signal transduction molecule, results in decreased
      fibrosis in animal models. In recent years, clinical advances have occurred in
      parallel with a better understanding of the underlying disease mechanisms. In
      this article, the immunological aspects and multiple altered immunological
      processes found in SSc are discussed.

PMID- 16987825
TI  - Therapeutic modulation of cutaneous autoimmunity by regulatory T cells.
AB  - Cutaneous autoimmunity is characterized by the presence of autoantibodies and/or
      autoreactive T cells. Several mechanisms have been developed to avoid loss of
      immunotolerance to self such as activation-induced cell death, deletion,
      ignorance and active suppression of autoreactivity. Regulatory ('suppressor') T
      cells play a pivotal role in inhibiting the activation and function of effector T
      cells. CD4(+)CD25(+) T cells constitute a subset of regulatory T cells, which
      have been shown to suppress the development of organ-specific autoimmunity in
      mice. Recent understanding in the generation and function of human regulatory T
      cells indicates that these cells are involved in the appearance of inflammatory
      as well as bullous autoimmune dermatosis. These findings suggest that modulation
      of regulatory T cell numbers or function might be a promising therapeutic
      alternative for the treatment of such disorders. In the following, recent
      strategies aimed at inducing antigen-specific or non-specific regulatory T cells
      for the immunotherapy of ongoing cutaneous autoimmunity are presented and
      discussed. Hopefully, pursuing these strategies in the future will result in the
      initiation of randomized clinical studies analysing the usefulness of regulatory
      T cells for human skin diseases in great detail.

PMID- 16987827
TI  - Angiogenesis and vasculogenesis in systemic sclerosis.
AB  - In addition to inflammatory infiltrates and an accumulation of extracellular
      matrix proteins, vascular changes are a hallmark in the pathogenesis of systemic
      sclerosis (SSc). Consistent with the ongoing endothelial cell apoptosis, several
      markers of EC damage are up-regulated in the serum of SSc patients. Surprizingly,
      vascular endothelial growth factor (VEGF), a very potent angiogenic molecule, is
      overexpressed in SSc patients despite the insufficient angiogenesis. VEGF can
      protect patients from fingertip ulcers, but a prolonged overexpression of VEGF
      might have paradoxical effects leading to the formation of irregular vessels
      similar to that observed in SSc. Besides defective angiogenesis, recent studies
      suggest that vasculogenesis is also impaired in SSc patients with reduced numbers
      and functional defects of endothelial progenitor cells.

PMID- 16987828
TI  - Systemic sclerosis in childhood.
AB  - Juvenile systemic sclerosis (jSSc) is a rare disease of childhood, and the amount
      of published data is limited. It appears that its clinical presentation differs
      from adult disease and the limited form affects only very few children. The organ
      involvement pattern differs also from the adult form. Prognosis seems to be
      better with a 5-yr survival of 95% of the jSSc patients. The validation of the
      outcome measures for children with jSSc is currently in progress. Regarding
      effective treatment, there are no paediatric data and the paediatric
      rheumatologist needs to rely on the experiences in adult disease.

PMID- 16987829
TI  - Epidemiology of connective tissue disorders.
AB  - The reported prevalence and incidence of connective tissue disorders are quite
      variable, depending on differences in study methodology. Most important
      differences are the study duration, the classification criteria used for
      diagnosis and the country in which the study was undertaken. Sjogren's syndrome
      has the highest prevalence ranging between 0.5 and 3% of a given population. The
      prevalence of systemic lupus erythematosus (SLE) is estimated between 15 and 50
      per 100 000 individuals, with a female:male ratio of 6-10:1 in the age group
      between 15 and 40 yrs. The prevalence of systemic sclerosis is lower, however,
      varying significantly between different studies and countries. The prevalence of
      overlap syndromes, especially mixed connective tissue disease, is unknown, and
      polymyositis and dermatomyositis are regarded as very rare rheumatic diseases.
      Though the classification criteria for the connective tissue disorders have not
      been developed for the purpose of diagnosing an individual patient, these
      criteria still are the most valuable tool for the identification of patients with
      systemic rheumatic diseases such as connective tissue disorders.

PMID- 16987830
TI  - Connective tissue diseases and pregnancy.
AB  - Connective tissue diseases (CTD) such as systemic lupus erythematosus diffuse or
      limited systemic sclerosis and numerous others affect women frequently during the
      childbearing period. Every pregnancy in a patient with CTD should be regarded as
      high-risk pregnancy, and requires intensive monitoring and immediate treatment of
      clinical problems. For these reasons, for women suffering from CTD, who are
      pregnant or who intend to become pregnant, an interdisciplinary setting
      addressing all aspects of rheumatology, ob-gyn and neonatalogy needs to be
      provided. This setting includes particular diagnostic tools and laboratory
      parameters prior to and during pregnancy as well as in the post-partal period.
      Aside overt organ dysfunction, key problems in pregnant CTD patients consist
      mainly of haemostaseological problems such as antiphospholipid antibodies,
      neonatal lupus erythematosus, congenital heart block and drug therapy of the
      underlying disease, which will be outlined in this review.

PMID- 16987831
TI  - Pathophysiology and clinical consequences of Raynaud's phenomenon related to
      systemic sclerosis.
AB  - According to the so-called vascular hypothesis, Raynaud's phenomenon (RP) is one
      initial event in the pathophysiological cascade leading to sclerosis in systemic
      sclerosis (SSc). It is characterized by recurrent, reversible spasms of small
      arterioles and digital arteries, usually triggered by cold and emotional stress.
      Clinical signs of RP are a sudden pallor of single digits of fingers followed by
      reactive hyperaemia and in severe cases also by cyanosis. Besides imbalances
      between vasoconstrictive and vasodilatory processes, structural alterations of
      the involved vessels are fundamental to secondary RP in SSc. The latter is the
      reason why secondary RP in SSc, in contrast to primary RP, often leads to
      ischaemia and re-perfusion injuries. New insights into the pathophysiology of RP
      feature a special role for alpha2c-adrenoreceptors, Rho-kinase signalling
      pathways and soluble mediators. They have resulted in promising therapeutic
      options, including antagonism of endothelin receptors, inhibition of
      phosphodiesterases or selective blockade of alpha2c-adrenoreceptors. They should
      also have a positive impact on the course of SSc in general.

PMID- 16987832
TI  - Role of endothelin in chronic renal failure--developments in renal involvement.
AB  - Endothelin (ET)-1 is a potent vasoconstrictor with profibrotic and
      proinflammatory effects. Increasing evidence suggests that ET-1 and its cognate
      receptors are involved in a variety of progressive renal disorders, including
      diabetes, hypertension and glomerulonephritis. Several laboratory studies have
      demonstrated elevated expression of ET-1, which colocalizes with glomerular and
      tubulointerstitial injury, in addition to enhanced urinary excretion. Moreover,
      ET-1 expression correlates with disease severity and renal function. With the
      availability of ET receptor antagonists, a pathogenetic role has been further
      corroborated in animal models, demonstrating both structural and functional
      improvement. Thus, antagonizing the ET system may be useful in major renal
      pathologies associated with glomerular and tubulointerstitial damage.

PMID- 16987833
TI  - Endothelin in human autoimmune diseases with renal involvement.
AB  - Endothelin (ET)-1 is a potent renal vasoconstrictor with pro-inflammatory,
      profibrotic and mitogenic potential. Animal studies support a pathogenetic
      contribution of ET-1 and its cognate receptors in several renal manifestations of
      autoimmune disorders. However, data in humans are limited. The present minireview
      thus summarizes the observations available in humans. Similar to animal models,
      ET-1 is overexpressed in glomerular and tubulointerstitial lesions, which is
      reflected by an increased urinary excretion of ET-1. Since antagonizing the ET
      system has beneficial effects in experimental models, this approach may be
      translated to the human kidney, thus counteracting vasoconstriction, inflammation
      and extracellular matrix deposition during the course of human autoimmune
      disease.

PMID- 16987834
TI  - The role of DMARDs in systemic sclerosis therapy.
AB  - The aim of this review is to evaluate the evidence for disease-modifying anti
      rheumatic drugs (DMARDs) for treatment of systemic sclerosis (SSc). In the
      previously published trials, DMARD therapy was usually initiated for severe skin
      thickening, organ involvement and alveolitis. These studies suggest beneficial
      effects of methotrexate, azathioprine, ciclosporine A and cyclophosphamide
      therapy in SSc patients. However, many of these data were derived from
      retrospective analyses with low numbers of patients, short-term follow-up and
      often without an appropriate control group. Finally, some of these studies led to
      inconsistent results. At the present time there is no DMARD therapy of proven
      efficacy in SSc. Immunosuppressive therapy should only be considered in patients
      with early diffuse disease, overlap syndromes or pulmonary fibrosis. Current
      expert recommendations suggest a therapy with methotrexate for skin thickening or
      cyclophosphamide for acute alveolitis. However, more clinical trials with larger
      numbers of patients with recent onset SSc are needed.

PMID- 16987835
TI  - Successful treatment of patients with severe secondary Raynaud's phenomenon with
      the endothelin receptor antagonist bosentan.
AB  - Secondary Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc) and
      other collagen vascular diseases is a serious manifestation of microvascular
      damage that may precede the onset of visceral and/or cutaneous sclerosis for
      years. Recent studies have demonstrated that the endothelin receptor antagonist
      bosentan prevents the development of new digital ulcers in SSc. We investigated
      the potential benefits of bosentan in patients with secondary RP associated with
      pre-scleroderma and with SSc, independent of digital ulcers. Three patients with
      secondary RP received bosentan 62.5 mg twice daily for 4 weeks followed by 125 mg
      twice daily for 12 weeks during the winter season. Pain (visual analogue scale),
      Raynaud's disease activity (Scleroderma Health Assessment Questionnaire), number
      and severity of daily Raynaud's attacks (diary) and peripheral thermoregulation
      (thermography) were assessed during treatment periods. Pain, Raynaud's disease
      activity, number and severity of Raynaud's attacks significantly decreased during
      treatment periods. Thermography after 16-week treatment demonstrated improved
      peripheral thermoregulation. Although this is a small observational study,
      treatment with bosentan appears to measurably reduce the daily impact of
      Raynaud's disease and improve peripheral thermoregulation in patients with
      secondary RP, independent of digital ulcers.

PMID- 16987836
TI  - Vasoactive therapies in systemic sclerosis.
AB  - In systemic sclerosis (SSc), vasculopathy is a central mechanism and is a major
      initial event in the process of sclerosis and causing different complications
      such as Raynaud's phenomenon, ulcer(s) or pulmonary hypertension, the latter
      being life threatening. Therefore, vasoactive therapies are important when taking
      care of patients with SSc. However, as treatment has been difficult, numerous
      therapeutic modalities have been suggested. Until now, the interpretation of most
      studies is limited due to the heterogeneity of patient groups, the low number of
      patients, the short duration of the treatments and, possibly, further pathogenic
      mechanisms such as autoimmunity. Several drugs are now available with effects on
      vasculopathy and, furthermore, on specific pathogenic mechanisms in SSc.
      Prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors
      have potential effects on fibrosis, inflammation and endothelial cells,
      suggesting a disease-modifying capacity in systemic sclerosis. This review
      summarizes evidence-based therapy recommendations.

PMID- 16987837
TI  - Connective tissue diseases: evaluation of clinical response.
AB  - Systemic connective tissue diseases (CTDs) are disease entities characterized by
      a systemic and heterogeneous spectrum of clinical symptoms. The treatment of CDTs
      has improved substantially, but with the developments of new and probably more
      expensive targeted therapies, there will be a need of rigorous evaluation in
      patient-oriented research. Proposed domains for outcome measurement of CTDs are
      activity, damage by disease and/or medications and quality of life. To evaluate
      the overall disease activity in CTDs, scores are developed that include typical
      signs and symptoms. For example, in systemic lupus erythematosus (SLE), various
      activity instruments have been developed and validated. Recently, a definition
      for significant reduction in activity based on these scores was proposed and has
      now to be validated in clinical trials. In addition, the American College of
      Rheumatology has framed recommendations for response criteria of major target
      organs. Besides, the rarity of CTDs other than SLE and the rare therapeutic
      options, especially the heterogeneous disease expression, has prevented
      development of instruments scoring the disease activity. In individual patients,
      there is need for a more organ-specific evaluation, and non-disease-specific
      and/or global health instruments may be used in evaluating the response of
      individual treatment regimen.

PMID- 16987838
TI  - Phototherapy: a promising treatment option for skin sclerosis in scleroderma?
AB  - In systemic sclerosis (SSc; scleroderma) fibrosis of the skin can lead to
      considerable morbidity. No significant improvement has been reported from studies
      investigating antifibrotic therapies so far. In dermatology, phototherapy with
      ultraviolet (UV) irradiation is successfully used for treatment of several
      diseases because of its anti-inflammatory as well as immunosuppressive
      mechanisms, and its low-risk profile. In addition, the UVA spectrum in particular
      exerts antifibrotic effects as it leads to reduction of procollagen synthesis and
      expression of collagenase-1 in vitro. Accordingly, treatment with long-wavelength
      UVA-1 irradiation or photochemotherapy with UVA plus the photosensitizer psoralen
      (PUVA) have been successfully used to reduce skin fibrosis in localized
      scleroderma (morphea). There are only in particular few reports on treatment of
      skin sclerosis in SSc, but the results are in concordance with the good
      experience that have been observed at our and other dermatological centres.
      Phototherapy is able to stop or inhibit the fibrotic processes and to induce
      softening of sclerotic skin, especially in limited SSc. Phototherapy thus
      represents a therapeutic alternative for antifibrotic treatment with a low rate
      of adverse effects, which should be applied before the sclerotic process has
      proceeded too far.

PMID- 16987839
TI  - The role of endothelin in connective tissue diseases.
AB  - Vascular dysregulation is centrally involved in the pathogenesis of diverse
      rheumatological diseases. The resulting pulmonary arterial hypertension as well
      as Raynaud's phenomenon may be accompanied by distinct tissue fibrosis. The
      pleiotropic cytokine endothelin may represent a link between these vascular and
      fibrotic processes, which are most evidently seen in systemic sclerosis. Among
      three closely related isoforms, endothelin-1 (ET-1) is the most common in humans,
      and is often referred to as ET in the literature. ET-1 is involved in
      physiological processes of vascular tone and mitogenesis, whereas under
      pathological conditions fibrosis, vascular hypertension and inflammation are
      induced. Its expression is dependent on tissue and cell type as well as on the
      underlying disease entity and its stage. Elevated plasma and tissue levels have
      been demonstrated in idiopathic pulmonary hypertension, systemic sclerosis as
      well as in other connective tissue diseases and correlate to haemodynamic
      parameters and disease outcome. The biological effects are mediated by two
      membrane receptors (ET-1-receptor A and B) belonging to the G-protein-coupled
      serpentine family. Both receptors are differentially expressed by different cell
      types as well as in different diseases entities. Antagonizing these receptors
      therapeutically has already been successful. However, the differential action of
      ET is counterbalanced by other mediators, prominently nitric oxide. Consequently,
      the suspected direct relation of vascular and fibrotic processes through ET still
      needs to be further evaluated.

PMID- 16987840
TI  - The population dynamics of cancer: a Darwinian perspective.
AB  - Carcinogenesis, at least for some types of cancer, can be interpreted as the
      consequence of selection of mutated cells similar to what, in the theory of
      evolution, occurs at the population level. Instead of considering a population of
      organisms, we can refer to a population of cells belonging to multicellular
      organisms. Many carcinogens are mutagens, and the observed geographic
      distribution of cancer is, at least in part, attributable to environmental
      mutagens. However, the rapid change in risk for some cancers after migration
      suggests that carcinogenesis involves--in addition to mutations--some late event
      that most probably consists of the selection of cells already carrying mutations.
      We review a few examples of such selective pressures: finasteride in prostate
      cancer, vitamin supplementation in smokers, acquired resistance to chemotherapy,
      peripheral resistance to insulin, and sunlight and mutations in melanoma. A
      disease model for such a hypothesis is represented by Paroxysmal Nocturnal
      Hemoglobinuria (PNH). Mutations can be present at birth, as in the case of PNH,
      and can have a frequency much higher than the occurrence of the corresponding
      disease (PNH or lymphocytic leukaemia in children). However, PNH does not require
      a mutator phenotype, only a mutant phenotype followed by selection. A
      characteristic feature of cancer, instead, is likely to be the development of the
      mutator phenotype. We propose a 'Darwinian' model of carcinogenesis. If the model
      is correct, it suggests that prevention is more complex than avoiding exposure to
      mutagens. Mutations and genetic instability can be already present at birth.
      Mutations can be selected in the course of life if they increase survival
      advantage of the cell under certain environmental circumstances. In addition,
      gene-environment interactions cannot be interpreted according to a simplified
      linear model (based on the 'analysis of variance' concept); experimental work
      suggests that a more comprehensive non-linear interpretation based on the idea of
      'norm of reaction' is needed.

PMID- 16987841
TI  - Citation indexes for science. A new dimension in documentation through
      association of ideas. 1955.

PMID- 16987842
TI  - It's not easy being interdisciplinary.

PMID- 16987843
TI  - Commentary: the power of the unrelenting impact factor--is it a force for good or
      harm?

PMID- 16987845
TI  - Commentary: inflamed about ultrafine particles?

PMID- 16987846
TI  - Commentary: the 'bibliographic impact factor' and the still uncharted sociology
      of epidemiology.

PMID- 16987848
TI  - Decomposing socioeconomic inequality in infant mortality in Iran.
AB  - BACKGROUND: Although measuring socioeconomic inequality in population health
      indicators like infant mortality is important, more interesting for policy
      purposes is to try to explain infant mortality inequality. The objective of this
      paper is to quantify for the first time the determinants' contributions of
      socioeconomic inequality in infant mortality in Iran. METHODS: A nationally
      representative sample of 108 875 live births from October 1990 to September 1999
      was selected. The data were taken from the Iranian Demographic and Health Survey
      (DHS) conducted in 2000. Households' socioeconomic status was measured using
      principal component analysis. The concentration index of infant mortality was
      used as our measure of socioeconomic inequality and decomposed into its
      determining factors. RESULTS: The largest contributions to inequality in infant
      mortality were owing to household economic status (36.2%) and mother's education
      (20.9%). Residency in rural/urban areas (13.9%), birth interval (13.0%), and
      hygienic status of toilet (11.9%) also proved important contributors to the
      measured inequality. CONCLUSIONS: The findings indicate that socioeconomic
      inequality in infant mortality in Iran is determined not only by health system
      functions but also by factors beyond the scope of health authorities and care
      delivery system. This implies that in addition to reducing inequalities in wealth
      and education, investments in water and sanitation infrastructure and programmes
      (especially in rural areas) are necessary to realize improvements of inequality
      in infant mortality across society. These findings can be instrumental for the
      recent 5 year Economic, Social and Cultural Development Plan of Iran, which
      identified the reduction of inequalities in social determinants of health.

PMID- 16987849
TI  - Progress through cooperation: securing a sound training pathway for perioperative
      transesophageal echocardiography.

PMID- 16987850
TI  - Hurry up and slow down: lessons in drug development from the COX-2 inhibitors.

PMID- 16987851
TI  - Transesophageal echocardiographic evaluation of ECG-guided central venous
      catheter placement.
AB  - PURPOSE: To facilitate electrocardiography (ECG)-guided central venous catheter
      placement by observing the shape and size of the P wave at specific locations of
      a central venous catheter (CVC) tip. METHODS: We evaluated 54 patients for whom
      central venous catheterization was planned as part of routine care for their
      elective surgery. The junction of the superior vena cava (SVC) and the right
      atrium (RA) was defined as the superior border of the crista terminalis by
      transesophageal echocardiography. The RA ECGs were recorded while withdrawing the
      CVC into the SVC or advancing it into the RA at 1-cm intervals. Saline was used
      as an electrical conductor via the distal lumen of the CVC. RESULTS: The tallest
      peaked and biphasic P waves [median (interquartile range)] were observed when the
      CVC tip was located at positions 0.0 cm (-1.0 to 0.0) and -4.0 cm (-5.0 to -3.0)
      below the SVC/RA junction, respectively. The P wave returned to a normal shape
      and size at 4.0 cm (3.0 to 4.0) above the SVC/RA junction. Overshoot P waves were
      observed at - 4.0 cm (-5.0 to -3.0) below the SVC/RA junction in 22 patients,
      when the CVC tip appeared to be contacting or in close proximity to the RA wall.
      CONCLUSIONS: During ECG-guided central venous catheterization, the tallest peaked
      P wave may be used to place the CVC tip at the SVC/RA junction, the normally
      shaped P wave identifies the mid to upper SVC, and biphasic P waves identify RA
      localization.

PMID- 16987852
TI  - Mivacurium-induced neuromuscular block in adult patients suffering from Charcot
      Marie-Tooth disease.
AB  - PURPOSE: The response to non-depolarizing neuromuscular blocking drugs is
      variable in patients with Charcot-Marie-Tooth (CMT) disease. We speculated that
      CMT involvement of the monitored muscle may be partially responsible for this
      inconsistency. We therefore investigated the response to a standard dose of
      mivacurium simultaneously assessed at adductor pollicis (AP) and orbicularis
      oculi (OO) muscles in five patients with CMT. CLINICAL FEATURES: Over a period of
      one year, five adult patients with CMT scheduled for orthopedic surgery were
      studied. The right arm and the right supercilliary arch were prepared for
      acceleromyographic (AMG) neuromuscular monitoring. The AMG probes were attached
      at the distal interphalangeal joint of the right thumb and on the right upper
      eyelid to record the response of the AP and OO, respectively. The ulnar nerve and
      upper part of the facial nerve were stimulated supramaximally with repeated train
      of-four stimuli (2 Hz, 0.2 msec) every 15 sec via applied surface electrodes.
      Following monitor calibration and induction of general anesthesia, mivacurium 0.2
      mg x kg(- 1) iv was given, and the time course of relaxation and recovery were
      assessed. Times to spontaneous recovery of T1 to 25% were 15 +/- 3 vs 12 +/- 4
      min in the AP and OO muscle groups respectively, whereas times to 90% recovery
      were 23 +/- 5 vs 29 +/- 10 min, respectively. CONCLUSION: The onset and recovery
      characteristics associated with mivacurium-induced neuromuscular block were
      similar at the AP and OO muscle groups. A near normal response to mivacurium was
      observed in this small series of patients with CMT disease.

PMID- 16987853
TI  - Case report: intraoperative anaphylactoid reaction and hydroxyethyl starch in
      balanced electrolyte solution (Hextend).
AB  - PURPOSE: To report a first case of probable anaphylactoid reaction to 6%
      hydroxyethyl starch reconstituted in balanced electrolyte and glucose solution
      (Hextend). CLINICAL FEATURES: A 22-yr-old man was admitted for a partial
      nephrectomy. Near the end of the four-hour operation, an infusion of Hextend was
      initiated. Shortly thereafter, mechanical ventilation became difficult, peak
      inspiratory pressure increased to 55 cm H2O with audible wheezing over the
      patient's lungs. Blood pressure suddenly decreased to 68/46 mmHg. Multiple doses
      of phenylephrine, ephedrine and epinephrine were required to restore the
      patient's blood pressure. Postoperatively, a diffuse urticarial rash was apparent
      on his upper torso. The patient recovered uneventfully. His postoperative serum
      tryptase was 26.3 ng x mL(-1) (reference range, < 11.5 ng x mL(-1)) and the urine
      N-methyl-histamine was 2448 microg x g(-1) creatinine (reference range, 30-200
      microg x g(-1) creatinine). Two months after the event, skin testing was
      conducted to test for possible allergy to latex, lidocaine, propofol,
      cisatracurium, succinylcholine, vecuronium, midazolam, fentanyl, ondansetron,
      neostigmine, and cephazolin, and all were negative. Hextend was also tested,
      starting with a 1:100,000 dilution and the results were negative. CONCLUSIONS:
      The temporal relationship of severe hypotension, bronchospasm and skin rash
      within ten minutes from administration of Hextend in this patient suggests an
      immediate hypersensitivity reaction to hetastarch. The elevated levels of serum
      tryptase and urinary N-methyl-histamine suggest that this hypersensitivity was
      mediated from mast cell degranulation. Negative skin testing suggests that the
      reaction was anaphylactoid.

PMID- 16987854
TI  - Brief review: angiotensin converting enzyme inhibitors and angioedema: anesthetic
      implications.
AB  - PURPOSE: Angiotensin converting enzyme inhibitors (ACEIs) are a group of drugs
      used to treat hypertension and heart failure, with additional benefits, such as
      cardiovascular and renal protection, in patients with diabetes. However,
      angioedema as a complication of ACEI therapy is under-recognized. As there are
      important implications for anesthesiologists and emergency medicine physicians, a
      review was undertaken to document the scope of the problem of ACEI-induced
      angioedema.. METHODS: A review of the published literature (identified by
      searching Medline, EMBASE and CINAHL) was undertaken, addressing the clinical
      uses of ACEIs and the incidence, risk factors, pathophysiology, clinical
      presentation and management of angioedema associated with the use of these drugs.
      PRINCIPAL FINDINGS: The incidence of ACEI related angioedema has increased from
      0.1-0.2% to 1% over the last decade. Patients who are receiving ACEIs are
      predisposed to developing angioedema which may be triggered by trauma, airway
      instrumentation, infection, and irritant fumes, particularly in those who are at
      increased risk. Cases of acute facial and airway oedema, due to ACEI drug
      administration, may be misdiagnosed as an anaphylactic reaction, and the
      association with ACEIs may be ignored. Some cases of intraoperative and
      postoperative airway edema may be precipitated by airway instrumentation in
      patients receiving ACEI drugs. The severity of airway compromise ranges from mild
      facial edema to severe laryngeal or subglottic edema which may prove life
      threatening. CONCLUSION: In view of the widespread clinical indications and ever
      increasing use of ACEI drugs, the potentially life-threatening adverse reaction
      of ACEI-associated angioedema, and its treatment, must be recognized by
      anesthesiologists and all clinicians involved in airway management.

PMID- 16987855
TI  - Analgesic effects of systemic midazolam: comparison with intrathecal
      administration.
AB  - PURPOSE: Midazolam has antinociceptive effects when administered intrathecally,
      while its effects associated with systemic administration remain controversial.
      In the present study, the antinociceptive properties of systemically vs
      intrathecally administered midazolam were investigated in a rat model of thermal
      and inflammatory pain. METHODS: One hundred seventy-six (n = 8 animals per dose
      escalation) male Sprague-Dawley rats were instrumented with lumbar intrathecal
      catheters. Tail withdrawal in response to thermal stimulation, or paw flinching
      and shaking in response to sc hind paw formalin injection were compared following
      intrathecal injection of midazolam (1, 3, 10, 30, or 100 microg in 10 microL) or
      ip administration (3, 30, 300, or 3,000 microg in 300 microL). Saline 10 microL
      or 300 microL was used as a control. Behavioural side effects and motor
      disturbance were also examined. RESULTS: Intrathecal administration of midazolam
      increased tail flick latency dose dependently (P < 0.05) with a 50% effective
      dose (ED50) of 1.60 microg, whereas ip administration did not increase latency.
      Both intrathecal and ip routes of administration decreased the number of paw
      flinches in both phases 1 and 2 of the formalin test (P < 0.05). The ED50s were
      1.26 microg [confidence interval (CI), 0.35-3.18 microg], (phase 1) and 1.20
      microg (CI, 0.29-3.71 microg), (phase 2) with intrathecal administration, and
      11.6 microg (CI, 2.5-19.3 microg), (phase 1) and 52.2 microg (CI, 18.3-102.7
      microg), (phase 2) with ip administration. CONCLUSION: Systemically administered
      midazolam induced antinociception for inflammatory pain only, while intrathecal
      administration elicited antinociceptive effects on both acute thermal and
      inflammatory-induced pain.

PMID- 16987856
TI  - Case report: epidural abscess in a parturient with pruritic urticarial papules
      and plaques of pregnancy (PUPPP).
AB  - PURPOSE: To describe the risk factors for epidural abscess (EA) formation
      following epidural analgesia in a parturient with pruritic urticarial papules and
      plaques of pregnancy (PUPPP). CLINICAL FEATURES: A 33 yr-old gravida 2
      nulliparous patient at 36 weeks gestation presented with severe pre-eclampsia,
      and PUPPP (treated with prednisone). Magnesium prophylaxis was started and labour
      was induced. An epidural catheter was placed at the L(3-4) level using standard
      aseptic technique. Bupivacaine was incrementally injected to achieve a T10
      sensory level, and analgesia was maintained using a continuous infusion of
      0.0625% bupivacaine with fentanyl. Nine days post-delivery, the patient developed
      back pain radiating to her right leg, but she was otherwise asymptomatic. She was
      afebrile; with a slightly tender, non-erythematous, non-draining, 1 cm nodule at
      the epidural catheter site. Motor and sensory examinations were normal at that
      time. However, the patient returned 24 hr later and further investigations
      revealed: WBC 17,800.mm(-3), platelets 486,000.mm(-3), erythrocyte sedimentation
      rate 50 mm.hr(-1), and C-reactive protein 8.8 mg.dL(-1). The magnetic resonance
      imaging demonstrated an EA at the L(3-4) level causing minimal cord compression.
      The patient underwent an emergency decompressive laminectomy. Cultures revealed
      methicillin-sensitive Staphylococcus aureus. Her pain improved, and she was
      discharged on the third postoperative day with a six-week course of iv
      ceftriaxone. CONCLUSION: Causative organisms for EAs include coagulase-negative
      Staphylococci, S. aureus, and Gram-negative bacilli. Infection can occur either
      hematogenously or by direct contamination during catheter placement. Risk factors
      include immunocompromised states and PUPPP, as with the case of this patient.

PMID- 16987857
TI  - Case report: cerebral vein thrombosis after subarachnoid analgesia for labour.
AB  - PURPOSE: We report a case of sagittal sinus thrombosis occurring after spinal
      analgesia for labour to highlight the difficulty of such diagnosis in the
      presence of postpartum atypical headache following regional anesthesia/analgesia.
      CLINICAL FEATURES: A previously healthy 21-yr-old, primiparous, preeclamptic
      parturient was admitted to the hospital at 37 weeks gestation for uterine
      contractions. Before pregnancy she was taking no medication other than oral
      contraceptives and was a non-smoker. Spinal analgesia was established on the
      first attempt at 8 cm of cervical dilation, in the setting of rapid progression
      of labour. Following an uneventful delivery, on the third day postpartum, the
      patient experienced gradual onset of an atypical headache with unclear postural
      character, followed by focal neurological signs five days later. Emergency
      neuroimaging revealed direct evidence of thrombosis in the posterior sagittal
      venous sinus. Anticoagulation was initiated with iv heparin (500 UI x kg(-1) x
      day(-1)). The patient's headache decreased progressively and full motor recovery
      was noted by day 14 postpartum. After 24 days, the patient was discharged without
      any neurological disability. Common inherited thrombophilic dispositions were
      absent, with the exception of a decrease in protein S level. CONCLUSION: Central
      venous thrombosis, while rare, is a recognized cause of puerperium stroke. The
      present case highlights the importance of considering the diagnosis in the
      presence of postpartum atypical headache following spinal anesthesia/analgesia.
      Early intervention with systemic heparinization is critical when the diagnosis is
      confirmed.

PMID- 16987858
TI  - Left and right ventricular diastolic dysfunction as predictors of difficult
      separation from cardiopulmonary bypass.
AB  - PURPOSE: As the evaluation of diastolic function can be complex in the setting of
      a busy cardiac operating room, its assessment may benefit from an algorithmic
      approach using transesophageal echocardiography. We developed a diagnostic
      algorithm which was then applied in a series of cardiac surgery patients to
      determine whether moderate to severe left ventricular diastolic dysfunction
      (LVDD) and right ventricular diastolic dysfunction (RVDD) can predict difficult
      separation from cardiopulmonary bypass (DSB). METHODS: An algorithm using pulsed
      wave Doppler interrogation of the mitral and tricuspid valve, the pulmonary and
      hepatic venous flow, and tissue Doppler interrogation of the mitral and tricuspid
      annulus was developed. The study was divided in two phases involving two groups
      of patients undergoing cardiac surgery. In phase I, echocardiographic evaluations
      of patients (n = 74) were used to test the reproducibility of the algorithm and
      to evaluate inter-observer variability using Cohen's kappa values which were
      calculated in three specific periods. In phase II, the algorithm was applied to a
      second group of patients (validation group, n = 179) to explore its prognostic
      significance. The primary end-point in phase II was DSB. RESULTS: In phase I, the
      kappa coefficients for LVDD and RVDD algorithms were 0.77 and 0.82, respectively.
      In phase II, moderate or severe degrees of LVDD were observed in 29 patients
      (16%) and moderate to severe RVDD was observed in 18 patients (10%) before
      cardiac surgery. Both moderate and severe LVDD (P = 0.017) and RVDD (P = 0.049)
      before surgery were observed more frequently in patients with DSB. CONCLUSION:
      Moderate and severe LVDD and RVDD can be identified with very good
      reproducibility, and both degrees of diastolic dysfunction are associated with
      DSB.

PMID- 16987859
TI  - Effect of oxygen affinity and molecular weight of HBOCs on cerebral oxygenation
      and blood pressure in rats.
AB  - PURPOSE: This study assessed the effect of oxygen affinity and molecular weight
      (MW) of o-raffinose cross-linked hemoglobin based oxygen carriers (HBOCs) on
      cerebral oxygen delivery and mean arterial blood pressure (MAP) following
      hemorrhage and resuscitation in rats. METHODS: Isoflurane anesthetized rats (n =
      6-7 per group) underwent 30% hemorrhage and resuscitation with an equivalent
      volume of one of three different HBOCs: 1) High P50 Poly o-raffinose hemoglobin
      (Poly OR-Hb, P50 = 70 mmHg); 2) High P50 > 128 Poly OR-Hb (MW > 128 kDa, P50 = 70
      mmHg) and 3) Low P50 > 128 Poly OR-Hb (MW >128 kDa, P50 = 11 mmHg). Hippocampal
      cerebral tissue oxygen tension, regional cerebral blood flow (rCBF), MAP, total
      hemoglobin concentration and arterial blood gases were measured. Data analysis by
      two-way ANOVA and post hoc Tukey tests determined significance (P < 0.05, mean +/
      SD). RESULTS: Hippocampal tissue oxygen tension increased in all HBOC groups
      following resuscitation. The rCBF remained unchanged after HBOC resuscitation in
      all groups. Following resuscitation, the peak MAP was higher in the High P50 Poly
      OR-Hb group (152 +/- 13 mmHg) when compared to either the Low or High P50 large
      MW, (> 128 kDa) HBOC group (119 +/- 15 mmHg or 127 +/- 18 respectively, P < 0.05
      for both). CONCLUSIONS: O-raffinose polymerized HBOC, with or without lower MW
      components, maintained cerebral tissue oxygen delivery following hemorrhage and
      resuscitation in rats. The higher MW HBOCs showed a decrease in peak MAP, which
      did not alter oxygen delivery. No significant effect of oxygen affinity on
      cerebral tissue oxygen tension or blood flow was observed.

PMID- 16987860
TI  - Case report: inferior vena-cava right atrial anastomotic stenosis after bicaval
      orthotopic heart transplantation.
AB  - PURPOSE: This case report describes the occurrence of acute postoperative liver
      and renal failure after bicaval orthotopic heart transplantation (OHT) due to
      stenosis of the inferior vena cava (IVC)-right atrial (RA) anastomosis. We also
      discuss the role of measuring femoral venous pressure and transesophageal
      echocardiography (TEE) in establishing the diagnosis. CLINICAL FEATURES: A 42-yr
      old female patient with idiopathic dilated cardiomyopathy underwent an OHT, using
      the bicaval anastomotic technique. During the first 12 hr postoperatively she
      developed unexplained kidney and liver failure. Her left and right ventricular
      functions were excellent and the right and left sided filling pressures were
      normal. The femoral pressure was elevated while the RA pressure was normal. An
      emergent TEE showed colour-flow and Doppler characteristics consistent with IVC
      RA anastomotic stenosis. Emergent surgical re-exploration was undertaken; a
      hemostatic suture was found at the RA cannulation site that had caused the
      constriction of the IVC-RA anastomosis. CONCLUSIONS: Acute liver and renal
      failure after OHT can have multiple causes including ischemia due to a low flow
      state. This case demonstrates the importance of doing a detailed intraoperative
      TEE after OHT, and the importance of repeating the intraoperative examination
      after any hemostatic sutures are placed. Femoral venous pressure monitoring can
      be a useful diagnostic tool in detecting IVC-RA stenosis.

PMID- 16987861
TI  - Canadian guidelines for training in adult perioperative transesophageal
      echocardiography. Recommendations of the Cardiovascular Section of the Canadian
      Anesthesiologists' Society and the Canadian Society of Echocardiography.
AB  - PURPOSE: To establish Canadian guidelines for training in adult perioperative
      transesophageal echocardiography (TEE). METHODS: Guidelines were established by
      the Canadian Perioperative Echocardiography Group with the support of the
      cardiovascular section of the Canadian Anesthesiologists' Society (CAS) in
      conjunction with the Canadian Society of Echocardiography. Guidelines for
      training in echocardiography by the American Society of Echocardiography, the
      American College of Cardiology and the Society of Cardiovascular
      Anesthesiologists were reviewed, modified and expanded to produce the 2003 Quebec
      expert consensus for training in perioperative echocardiography. The Quebec
      expert consensus and the 2005 Guidelines for the provision of echocardiography in
      Canada formed the basis of the Canadian training guidelines in adult
      perioperative TEE. RESULTS: Basic, advanced and director levels of expertise were
      identified. The total number of echocardiographic examinations to achieve each
      level of expertise remains unchanged from the 2002 American Society of
      Echocardiography-Society of Cardiovascular Anesthesiologists guidelines. The
      increased proportion of examinations personally performed at basic and advanced
      levels, and the level of autonomy at the basic level suggested by the Quebec
      expert consensus are retained. These examinations can be performed in a
      perioperative setting and are not limited to intraoperative TEE. Training "on the
      job", the role of the perioperative transesophageal echocardiography examination,
      requirements for maintenance of competence, and duration of training are also
      discussed for each level of training. The components of a TEE report and
      comprehensive TEE examination are also outlined. CONCLUSION: The Canadian
      guidelines for training in adult perioperative TEE reflect the unique Canadian
      practice profile in perioperative TEE and address the training requirements to
      obtain expertise in this field.

PMID- 16987862
TI  - Must the entire brain be dead to diagnose brain death?

PMID- 16987863
TI  - Meningismus after metaraminol administration in a patient with Familial
      Mediterranean fever.

PMID- 16987864
TI  - Glidescope/gastric-tube guided technique: a back-up approach for ProSeal LMA
      insertion.

PMID- 16987865
TI  - Less invasive cardiac output monitoring for OPCAB surgery.

PMID- 16987866
TI  - Sequential treatment with lamivudine and interferon-alpha monotherapies in
      hepatitis B e antigen-negative Chinese patients and its suppression of lamivudine
      resistant mutations.
AB  - OBJECTIVES: To assess the efficacy of sequential treatment with lamivudine and
      interferon-alpha monotherapies in Chinese patients with hepatitis B e antigen
      (HBeAg)-negative chronic hepatitis B. METHODS: One hundred and sixty-two patients
      with HBeAg-negative chronic hepatitis B were included in this study. Ninety-eight
      were treated with lamivudine alone (100 mg per day) for 48 weeks (group B). Sixty
      four were treated with lamivudine alone (100 mg per day) for 20 weeks, then
      combined with interferon-alpha-2b (5 million units three times per week) for 4
      weeks and then treated for another 24 weeks with interferon-alpha-2b alone (5
      million units three times per week) (group A). All patients were followed for an
      additional 24 weeks. RESULTS: After 48 weeks of treatment, the percentage of
      patients with normalization of alanine aminotransferase (ALT) levels or hepatitis
      B virus (HBV) DNA levels below 1000 copies/mL was not significantly different
      between the lamivudine monotherapy group (55.10% and 55.10%, respectively) and
      the sequential treatment group (59.36% and 56.25%, respectively). The percentage
      of patients with normalized ALT levels was significantly higher in group A (53%)
      than in group B (36%) at week 72 (P<0.05). The percentage of patients with
      lamivudine-resistant mutations was significantly higher with lamivudine
      monotherapy (22.45%) than with sequential therapy (P<0.05). CONCLUSIONS:
      Sequential treatment of chronic hepatitis B with lamivudine and interferon-alpha
      monotherapies is as effective as lamivudine-alone treatment in Chinese patients.
      However, sequential treatment can significantly suppress the emergence of
      lamivudine-resistant mutations.

PMID- 16987867
TI  - In vitro activity and synergism of amphotericin B, azoles and cationic
      antimicrobials against the emerging pathogen Trichoderma spp.
AB  - OBJECTIVES: The uncommon fungal pathogen Trichoderma shows increasing medical
      importance particularly in immunocompromised patients. Despite systemic
      antifungal therapy, prognosis of Trichoderma infection is poor regardless of the
      type of infection and the therapy used. The aim of the present study was to
      evaluate the in vitro activity and synergism of double antifungal combinations
      including amphotericin B, voriconazole, fluconazole, chlorhexidine digluconate
      and Akacid plus against 15 isolates of Trichoderma longibrachiatum and 1 isolate
      of Trichoderma harzianum. METHODS: Individual MICs were determined by using broth
      microdilution method following the NCCLS M38-A guidelines with standard RPMI 1640
      broth. Synergy tests were performed using the chequerboard method. RESULTS: All
      clinical Trichoderma strains showed reduced susceptibility to fluconazole
      (MICs>or=64 mg/L) and amphotericin B (MICs=2 mg/L), whereas lower MICs of 0.5-1
      mg/L were detected for voriconazole. Akacid plus reached the lowest MIC values in
      a range of 0.06-0.5 mg/L, 4- to 32-fold higher MICs were found for chlorhexidine.
      No antagonism was observed for any of the antifungal combinations tested.
      Interaction of amphotericin B and azoles was indifferent (fractional inhibitory
      concentration index, FICI 2-4). The combination of one azole and one cationic
      biocide showed different degree of synergism (FICI 0.07-2.03). Interaction of
      Akacid plus and chlorhexidine resulted in synergism for each Trichoderma isolate
      (FICI-range 0.05-0.5). CONCLUSIONS: These results demonstrate no interaction
      between antifungals and some degree of synergism between azoles and cationic
      antimicrobials against Trichoderma spp.

PMID- 16987868
TI  - Cardioblast-intrinsic Tinman activity controls proper diversification and
      differentiation of myocardial cells in Drosophila.
AB  - The NK homeobox gene tinman (tin) is required for the specification of the
      cardiac, visceral muscle and somatic muscle progenitors in the early dorsal
      mesoderm of Drosophila. Like its vertebrate counterpart Nkx2.5, the expression of
      tin is maintained in cardiac cells during cardiac maturation and differentiation;
      however, owing to the complete lack of a dorsal vessel in tin mutant embryos, the
      function of tin in these cells has not been defined. Here we show that myocardial
      cells and dorsal vessels can form even though they lack Tin, and that viable
      adults can develop, as long as Tin is provided in the embryonic precardiac
      mesoderm. However, embryos in which tin expression is specifically missing from
      cardial cells show severe disruptions in the normal diversification of the
      myocardial cells, and adults exhibit severe defects in cardiac remodeling and
      function. Our study reveals that the normal expression and activity of Tin in
      four of the six bilateral cardioblasts within each hemisegment of the heart
      allows these cells to adopt a cell fate as ;working' myocardium, as opposed to a
      fate as inflow tract (ostial) cells. This function of tin involves the repression
      of Dorsocross (Doc) T-box genes and, hence, the restriction of Doc to the Tin
      negative cells that will form ostia. We conclude that tin has a crucial role
      within myocardial cells that is required for the proper diversification,
      differentiation, and post-embryonic maturation of cardiomyocytes, and we present
      a pathway involving regulatory interactions among seven-up, midline, tinman and
      Dorsocross that establishes these developmental events upon myocardial cell
      specification.

PMID- 16987869
TI  - Cadherin is required for dendritic morphogenesis and synaptic terminal
      organization of retinal horizontal cells.
AB  - Dendrite morphology of neurons provides a structural basis for their
      physiological characteristics, and is precisely regulated in a cell type
      dependent manner. Using a unique transposon-mediated gene transfer system that
      enables conditional and cell-type specific expression of exogenous genes, we
      investigated the role of cadherin on dendritic morphogenesis of horizontal cells
      in the developing chicken retina. We first visualized single horizontal cells by
      overexpressing membrane-targeted EGFP, and confirmed that there were three
      subtypes of horizontal cells, the dendritic terminals of which projected to
      distinct synaptic sites in the outer plexiform layer. Expression of a dominant
      negative cadherin decreased the dendritic field size, and perturbed the
      termination of dendritic processes onto the photoreceptor cells. The cadherin
      blockade also impaired the accumulation of GluR4, a postsynaptic marker, at the
      cone pedicles. We thus provide in vivo evidence that cadherin is required for
      dendrite morphogenesis of horizontal cells and subsequent synapse formation with
      photoreceptor cells in the vertebrate retina.

PMID- 16987870
TI  - Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal
      pigment epithelium.
AB  - Shroom family proteins have been implicated in the control of the actin
      cytoskeleton, but so far only a single family member has been studied in the
      context of developing embryos. Here, we show that the Shroom-family protein,
      Shroom2 (previously known as APXL) is both necessary and sufficient to govern the
      localization of pigment granules at the apical surface of epithelial cells. In
      Xenopus embryos that lack Shroom2 function, we observed defects in pigmentation
      of the eye that stem from failure of melanosomes to mature and to associate with
      the apical cell surface. Ectopic expression of Shroom2 in naive epithelial cells
      facilitates apical pigment accumulation, and this activity specifically requires
      the Rab27a GTPase. Most interestingly, we find that Shroom2, like Shroom3
      (previously called Shroom), is sufficient to induce a dramatic apical
      accumulation of the microtubule-nucleating protein gamma-tubulin at the apical
      surfaces of naive epithelial cells. Together, our data identify Shroom2 as a
      central regulator of RPE pigmentation, and suggest that, despite their diverse
      biological roles, Shroom family proteins share a common activity. Finally,
      because the locus encoding human SHROOM2 lies within the critical region for two
      distinct forms of ocular albinism, it is possible that SHROOM2 mutations may be a
      contributing factor in these human visual system disorders.

PMID- 16987871
TI  - Cholinergic neuronal defect without cell loss in Huntington's disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG-repeat
      expansion in the huntingtin (IT15) gene. The striatum is one of the regions most
      affected by neurodegeneration, resulting in the loss of the medium-sized spiny
      neurons. Traditionally, the large cholinergic striatal interneurons are believed
      to be spared. Recent studies demonstrate that neuronal dysfunction without cell
      death also plays an important role in early and mid-stages of the disease. Here,
      we report that cholinergic transmission is affected in a HD transgenic mouse
      model (R6/1) and in tissues from HD patients. Stereological analysis shows no
      loss of cholinergic neurons in the striatum or septum in R6/1 mice. In contrast,
      the levels of mRNA and protein for vesicular acetylcholine transporter (VAChT)
      and choline acetyltransferase (ChAT) are decreased in the striatum and cortex,
      and acetylcholine esterase activity is lowered in the striatum of R6/1 mice
      already at young ages. Accordingly, VAChT is also reduced in striatal tissue from
      patients with HD. The decrease of VAChT in the patient samples studied is
      restricted to the striatum and does not occur in the hippocampus or the spinal
      cord. The expression and localization of REST/NRSF, a transcriptional regulator
      for the VAChT and ChAT genes, are not altered in cholinergic neurons. We show
      that the R6/1 mice exhibit severe deficits in learning and reference memory.
      Taken together, our data show that the cholinergic system is dysfunctional in
      R6/1 and HD patients. Consequently, they provide a rationale for testing of pro
      cholinergic drugs in this disease.

PMID- 16987872
TI  - New techniques to understand chromosome dosage: mouse models of aneuploidy.
AB  - Aberrations in human chromosome copy number and structure are common and
      extremely deleterious. Their downstream effects on phenotype are caused by
      aberrant dosage of sequences in the affected regions. However, we know little
      about why the abnormal gene copy number causes disease or why specific features
      result from deficits in specific chromosomes. Mice are the organism of choice to
      help us try to tease apart the complex relationships between genotype and
      phenotype in aneuploidy and segmental aneusomy syndromes. As new technologies
      such as chromosome engineering and the creation of transchromosomic mice become
      routine, these will help us identify individual dosage-sensitive genes that are
      causative in specific syndromes and will enable us to produce mouse models to
      accurately recapitulate human chromosomal disorders.

PMID- 16987873
TI  - The genetics of mental retardation.
AB  - Genetic abnormalities frequently give rise to a mental retardation phenotype.
      Recent advances in resolution of comparative genomic hybridization and genomic
      sequence annotation has identified new syndromes at chromosome 3q29 and 9q34. The
      finding of a significant number of copy number polymorphisms in the genome in the
      normal population, means that assigning pathogenicity to deletions and
      duplications in patients with mental retardation can be difficult but has been
      identified for duplications of MECP2 and L1CAM. Novel autosomal genes that cause
      mental retardation have been identified recently including CC2D1A identified by
      homozygosity mapping. Several new genes and pathways have been identified in the
      field of X-linked mental retardation but many more still await identification.
      Analysis of families where only a single male is affected reveals that the chance
      of this being due to a single X-linked gene abnormality is significantly less
      than would be expected if the excess of males in the population is entirely due
      to X-linked disease. Recent identification of novel X-linked mental retardation
      genes has identified components of the post-synaptic density and multiple zinc
      finger transcription factors as disease causing suggesting new mechanisms of
      disease causation. The first therapeutic treatments of animal models of mental
      retardation have been reported, a Drosophila model of Fragile X syndrome has been
      treated with lithium or metabotropic glutamate receptor (mGluR) antagonists and a
      mouse model of NF1 has been treated with the HMG-CoA reductase inhibitor
      lavastatin, which improves the learning and memory skills in these models.

PMID- 16987874
TI  - Genetic susceptibility to myocardial infarction and coronary artery disease.
AB  - Atherosclerotic involvement in the coronary arteries, which can result in heart
      attack and sudden death, is a common disease and prototypic of a complex human
      trait. To understand its genomic basis, eight linkage studies of sibling pairs
      have been performed. Although there was limited inter-study concordance of
      important loci, two gene variants in the leukotriene pathway (ALOX5AP and LTA4)
      have emerged as susceptibility factors for myocardial infarction (MI). Genome
      wide association studies have also been undertaken, and the pro-inflammatory
      cytokine lymphotoxin-alpha (LTA), and its key ligand galectin-2 (LGALS2) have
      been identified as genes implicated in predisposition for heart attack. By cueing
      into the genomic basis for low serum LDL cholesterol levels, much work has been
      done to advance the importance of the serine protease PCSK9, which modulates LDL
      receptor function. Lifelong lowered LDL cholesterol associated with PCSK9 point
      mutations in 2-3% of individuals have been shown to provide marked protection
      from coronary artery disease (CAD). Most of the success in this field has been
      with the phenotype of MI, which is considerably more restrictive than CAD. Four
      principal and interdependent processes--lipoprotein handling, endothelial
      integrity, arterial inflammation, and thrombosis--have been supported as
      important via the clustering of genes, thus far implicated in CAD susceptibility.
      Of note, connecting genes in a single pathway (leukotriene), of a protein and its
      ligand (LTAalpha) or from one disease to another [age-related macular
      degeneration (AMD); complement factor H (CFH)], or even three disease
      characterized by inflammation (MHC2) have now been reported. Although the
      population attributable risk for any of the genes identified to date is limited,
      such discovery is likely to be accelerated in the future.

PMID- 16987875
TI  - Genetics of obesity and the prediction of risk for health.
AB  - Obesity has always existed in human populations, but until very recently was
      comparatively rare. The availability of abundant, energy-rich processed foods in
      the last few decades has, however, resulted in a sharp rise in the prevalence of
      obesity in westernized countries. Although it is the obesogenic environment that
      has resulted in this major healthcare problem, it is acting by revealing a sub
      population with a pre-existing genetic predisposition to excess adiposity. There
      is substantial evidence for the heritability of obesity, and research in both
      rare and common forms of obesity has identified genes with significant roles in
      its aetiology. Application of this understanding to patient care has been slower.
      Until very recently, the health risks of obesity were thought to be well
      understood, with a straightforward correlation between increasing obesity and
      increasing risk of health problems such as type 2 diabetes, coronary heart
      disease, hypertension, arthritis and cancer. It is becoming clear, however, that
      the location of fat deposition, variation in the secretion of adipokines and
      other factors govern whether a particular obese person develops such
      complications. Prediction of the health risks of obesity for individual patients
      is not straightforward, but continuing advances in understanding of genetic
      factors influencing obesity risk and improved diagnostic technologies mean that
      the future for such prediction is looking increasingly bright.

PMID- 16987876
TI  - How lifetimes shape epigenotype within and across generations.
AB  - Despite our detailed characterization of the human genome at the level of the
      primary DNA sequence, we are still far from understanding the molecular events
      underlying phenotypic variation. Epigenetic modifications to the DNA sequence and
      associated chromatin are known to regulate gene expression and, as such, are a
      significant contributor to phenotype. Studies of inbred mice and monozygotic
      twins show that variation in the epigenotype can be seen even between genetically
      identical individuals and that this, in some cases at least, is associated with
      phenotypic differences. Moreover, recent evidence suggests that the epigenome can
      be influenced by the environment and these changes can last a lifetime. However,
      we also know that epigenetic states in real-time are in continual flux and, as a
      result, the epigenome exhibits instability both within and across generations. We
      still do not understand the rules governing the establishment and maintenance of
      the epigenotype at any particular locus. The underlying DNA sequence itself and
      the sequence at unlinked loci (modifier loci) are certainly involved. Recent
      support for the existence of transgenerational epigenetic inheritance in mammals
      suggests that the epigenetic state of the locus in the previous generation may
      also play a role. Over the next decade, many of these processes will be better
      understood, heralding a greater capacity for us to correlate measurable molecular
      marks with phenotype and providing the opportunity for improved diagnosis and
      presymptomatic healthcare.

PMID- 16987877
TI  - Epigenetics of autism spectrum disorders.
AB  - The autism spectrum disorders (ASD) comprise a complex group of behaviorally
      related disorders that are primarily genetic in origin. Involvement of epigenetic
      regulatory mechanisms in the pathogenesis of ASD has been suggested by the
      occurrence of ASD in patients with disorders arising from epigenetic mutations
      (fragile X syndrome) or that involve key epigenetic regulatory factors (Rett
      syndrome). Moreover, the most common recurrent cytogenetic abnormalities in ASD
      involve maternally derived duplications of the imprinted domain on chromosome
      15q11-13. Thus, parent of origin effects on sharing and linkage to imprinted
      regions on chromosomes 15q and 7q suggest that these regions warrant specific
      examination from an epigenetic perspective, particularly because epigenetic
      modifications do not change the primary genomic sequence, allowing risk
      epialleles to evade detection using standard screening strategies. This review
      examines the potential role of epigenetic factors in the etiology of ASD.

PMID- 16987878
TI  - Molecular bases of progeroid syndromes.
AB  - Progeroid syndromes (PSs) constitute a group of disorders characterized by
      clinical features mimicking physiological aging at an early age. In some of these
      syndromes, biological hallmarks of aging are also present, whereas in others, a
      link with physiological aging, if any, remains to be elucidated. These syndromes
      are clinically and genetically heterogeneous and most of them, including Werner
      syndrome and Hutchinson-Gilford progeria, are known as 'segmental aging
      syndromes', as they do not feature all aspects usually associated to
      physiological aging. However, all the characterized PSs enter in the field of
      rare monogenic disorders and several causative genes have been identified. These
      can be separated in subcategories corresponding to (i) genes encoding DNA repair
      factors, in particular, DNA helicases, and (ii) genes affecting the structure or
      post-translational maturation of lamin A, a major nuclear component. In addition,
      several animal models featuring premature aging have abnormal mitochondrial
      function or signal transduction between membrane receptors, nuclear regulatory
      proteins and mitochondria: no human pathological counterpart of these alterations
      has been found to date. In recent years, identification of mutations and their
      functional characterization have helped to unravel the cellular processes
      associated to segmental PSs. Recently, several studies allowed to establish a
      functional link between DNA repair and A-type lamins-associated syndromes,
      evidencing a relation between these syndromes, physiological aging and cancer.
      Here, we review recent data on molecular and cellular bases of PSs and discuss
      the mechanisms involved, with a special emphasis on lamin A-associated progeria
      and related disorders, for which therapeutic approaches have started to be
      developed.

PMID- 16987879
TI  - RNA-dominant diseases.
AB  - Several examples have come to light in which mutations in non-protein-coding
      regions give rise to a deleterious gain-of-function by non-coding RNA. Expression
      of the toxic RNA is associated with formation of nuclear inclusions and late
      onset degenerative changes in brain, heart or skeletal muscle. In the best
      studied example, myotonic dystrophy, it appears that the main pathogenic effect
      of the toxic RNA is to sequester binding proteins and compromise the regulation
      of alternative splicing. This review describes some of the recent advances in
      understanding the pathophysiology of RNA-dominant diseases.

PMID- 16987880
TI  - Signatures of adaptive evolution within human non-coding sequence.
AB  - The human genome is often portrayed as consisting of three sequence types, each
      distinguished by their mode of evolution. Purifying selection is estimated to act
      on 2.5-5.0% of the genome, whereas virtually all remaining sequence is considered
      to have evolved neutrally and to be devoid of functionality. The third mode of
      evolution, positive selection of advantageous changes, is considered rare. Such
      instances have been inferred only for a handful of sites, and these lie almost
      exclusively within protein-coding genes. Nevertheless, the majority of positively
      selected sequence is expected to lie within the wealth of functional 'dark
      matter' present outside of the coding sequence. Here, we review the evolutionary
      evidence for the majority of human-conserved DNA lying outside of the protein
      coding sequence. We argue that within this non-coding fraction lies at least 1 Mb
      of functional sequence that has accumulated many beneficial nucleotide
      replacements. Illuminating the functions of this adaptive dark matter will lead
      to a better understanding of the sequence changes that have shaped the innovative
      biology of our species.

PMID- 16987881
TI  - The genetic architecture of normal variation in human pigmentation: an
      evolutionary perspective and model.
AB  - Skin pigmentation varies substantially across human populations in a manner
      largely coincident with ultraviolet radiation intensity. This observation
      suggests that natural selection in response to sunlight is a major force in
      accounting for pigmentation variability. We review recent progress in identifying
      the genes controlling this variation with a particular focus on the trait's
      evolutionary past and the potential role of testing for signatures of selection
      in aiding the discovery of functionally important genes. We have analyzed SNP
      data from the International HapMap project in 77 pigmentation candidate genes for
      such signatures. On the basis of these results and other similar work, we provide
      a tentative three-population model (West Africa, East Asia and North Europe) of
      the evolutionary-genetic architecture of human pigmentation. These results
      suggest a complex evolutionary history, with selection acting on different gene
      targets at different times and places in the human past. Some candidate genes may
      have been selected in the ancestral human population, others in the 'out of
      Africa' proto European-Asian population, whereas most appear to have selectively
      evolved solely in either Europeans or East Asians separately despite the
      pigmentation similarities between these two populations. Selection signatures can
      provide important clues to aid gene discovery. However, these should be viewed as
      complements, rather than replacements of, functional studies including linkage
      and association analyses, which can directly refine our understanding of the
      trait.

PMID- 16987882
TI  - Recent advances in the genetics of amyotrophic lateral sclerosis and
      frontotemporal dementia: common pathways in neurodegenerative disease.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease classically
      defined by the impairment of the voluntary motor system and ubiquitin-positive
      intraneuronal aggregates in anterior horn cells. Frontotemporal dementia (FTD) is
      a common form of neurodegenerative dementia and presents with personality change
      associated in a significant subgroup of patients with cortical ubiquitin-only
      neuropathology (FTD-U). Careful study of ALS as well as FTD patient cohorts
      suggests clinical as well as pathological overlap of ALS with FTD. The idea that
      this reflects a shared pathogenesis has received strong support from the
      identification of new genetic loci on chromosome 9p and of mutations in specific
      genes (CHMP2B and DCN1) in families with co-segregation of ALS and FTD. The
      identification of two further genetic causes of FTD-U with (rare) ALS (PGRN) or
      without ALS (VCP) also provides a starting point for exploring the pathways
      associated with ubiquitin-mediated protein mishandling in FTD-U and ALS. Pure
      ALS, through ALS with cognitive impairment and ALS-FTD to pure FTD-U, may
      represent a continuous spectrum of ubiquitin-associated neurodegenerative
      disease.

PMID- 16987883
TI  - Untangling the tau gene association with neurodegenerative disorders.
AB  - Pathological tau protein inclusions have long been recognized to define the
      diverse range of neurodegenerative disorders called the tauopathies, which
      include Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and
      frontotemporal lobar degeneration. Mutations in the tau gene, MAPT, cause
      familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP
      17), and common variation in MAPT is strongly associated with the risk of PSP,
      corticobasal degeneration and, to a lesser extent, AD and Parkinson's disease
      (PD), implicating the involvement of tau in common neurodegenerative pathway(s).
      This review will discuss recent work towards the unravelling of the functional
      basis of this MAPT gene association. The region of chromosome 17q21 containing
      MAPT locus is characterized by the complex genomic architecture, including a
      large inversion that leads to a bipartite haplotype architecture, an inversion
      mediated deletion and multiplications resulting from non-allelic homologous
      recombination between the MAPT family of low-copy repeats.

PMID- 16987884
TI  - The many facets of the Wilms' tumour gene, WT1.
AB  - Over the years, many apparently contradictory findings and functions have been
      ascribed to the protein product of the WT1 tumour suppressor gene. These include
      being a transcriptional activator or repressor, a function in transcription
      versus RNA metabolism, and these days even a function as oncogene or tumour
      suppressor gene. To fully understand the role of WT1 in different diseases and
      normal development, we will need to understand these contradictions. In this
      review, we will discuss the present state of knowledge and suggest that a role
      for WT1 in influencing the mesenchymal-epithelial state of cells might be a
      common function that could explain many of the previously described findings.

PMID- 16987885
TI  - Type-2 diabetes: a cocktail of genetic discovery.
AB  - Diabetes is one of the most challenging health problems of the 21st century with
      an alarming increase in the prevalence of type-2 diabetes mellitus (T2DM) and
      associated conditions such as hypertension, dyslipidemias and obesity. T2DM is a
      complex genetic disease comprised of many metabolic disorders with a common
      phenotype of glucose intolerance. Patients with T2DM would have inherited a
      variety of different genetic factors that together with environmental factors
      combine as the primary cause. This complicates the genetic study of the disease
      and means that different methodological approaches are needed if we hope to
      identify susceptibility genes and genetic variants. The biochemical and
      physiological processes that underpin T2DM are still unclear although most
      certainly involve impairment in insulin secretion and insulin action. In this
      review, we will discuss the most exciting advances in understanding the genetics
      of T2DM by looking at recent discoveries employing human association studies and
      candidate genes arising from animal models.

PMID- 16987886
TI  - Signaling pathways in self-renewing hematopoietic and leukemic stem cells: do all
      stem cells need a niche?
AB  - Many adult tissue stem cells, such as the cells of the hematopoietic system,
      gastrointestinal epithelium, brain, epidermis, mammary gland and lung have now
      been identified, all of them fulfilling a crucial role in supplying organisms
      with mature cells during normal homeostasis as well as in times of tissue
      generation or repair. Two unique features characterize adult stem cells: the
      ability to generate new pluripotent stem cells (to self-renew) and the ability to
      give rise to differentiated progeny that has lost its self-renewal capacity. Our
      understanding of the mechanisms that determine whether, where and when a stem
      cell will self-renew or differentiate is still limited, but recent advances have
      indicated that the stem cell microenvironment, or niche, provides essential cues
      that direct these cell fate decisions. Moreover, loss of control over these cell
      fate decisions might lead to cellular transformation and cancer. This review
      addresses the current understandings of the molecular mechanisms that regulate
      hematopoietic stem cell self-renewal in the niche and how leukemic transformation
      might change the dependency of leukemic stem cells on their microenvironment for
      self-renewal and survival.

PMID- 16987887
TI  - Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein
      kinase signal transduction.
AB  - Noonan syndrome is a relatively common, genetically heterogeneous Mendelian trait
      with a pleiomorphic phenotype. Prior to the period covered in this review,
      missense mutations in PTPN11 had been found to account for nearly 50% of Noonan
      syndrome cases. That gene encodes SHP-2, a protein tyrosine kinase that plays
      diverse roles in signal transduction including signaling via the RAS-mitogen
      activated protein kinase (MAPK) pathway. Noonan syndrome-associated PTPN11
      mutations are gain-of-function, with most disrupting SHP-2's activation
      inactivation mechanism. Here, we review recent information that has elucidated
      further the types and effects of PTPN11 defects in Noonan syndrome and compare
      them to the related, but specific, missense PTPN11 mutations causing other
      diseases including LEOPARD syndrome and leukemias. These new data derive from
      biochemical and cell biological studies as well as animal modeling with fruit
      flies and chick embryos. The discovery of KRAS missense mutation as a minor cause
      of Noonan syndrome and the pathogenetic mechanisms of those mutants is discussed.
      Finally, the elucidation of gene defects underlying two phenotypically related
      disorders, Costello and cardio-facio-cutaneous syndromes is also reviewed. As
      these genes also encode proteins relevant for RAS-MAPK signal transduction, all
      of the syndromes discussed in this article now can be understood to constitute a
      class of disorders caused by dysregulated RAS-MAPK signaling.

PMID- 16987888
TI  - Planar cell polarity, ciliogenesis and neural tube defects.
AB  - Cilia are microtubule-based protrusions that are found on the surface of most
      vertebrate cells. Long studied by cell biologists, these organelles have recently
      caught the attention of developmental biologists and human geneticists. In this
      review, I will discuss recent findings suggesting a link between cilia and the
      planar cell polarity signaling cascade. In particular, I will focus on how this
      interaction may influence the process of neural tube closure and how these
      results may be relevant to our understanding of common human birth defects in
      which neural tube closure is compromised.

PMID- 16987889
TI  - Towards understanding CRUMBS function in retinal dystrophies.
AB  - Mutations in the Crumbs homologue 1 (CRB1) gene cause autosomal recessive
      retinitis pigmentosa (arRP) and autosomal Leber congenital amaurosis (arLCA). The
      crumbs (crb) gene was originally identified in Drosophila and encodes a large
      transmembrane protein required for maintenance of apico-basal cell polarity and
      adherens junction in embryonic epithelia. Human CRB1 and its two paralogues, CRB2
      and CRB3, are highly conserved throughout the animal kingdom. Both in Drosophila
      and in vertebrates, the short intracellular domain of Crb/CRB organizes an
      evolutionary conserved protein scaffold. Several lines of evidence, obtained both
      in Drosophila and in mouse, show that loss-of-function of crb/CRB1 or some of its
      intracellular interactors lead to morphological defects and light-induced
      degeneration of photoreceptor cells, features comparable to those observed in
      patients lacking CRB1 function. In this review, we describe how understanding Crb
      complex function in fly and vertebrate retina enhances our knowledge of basic
      cell biological processes and might lead to new therapeutic approaches for
      patients affected with retinal dystrophies caused by mutations in the CRB1 gene.

PMID- 16987890
TI  - Mitochondrial DNA polymerase-gamma and human disease.
AB  - The maintenance of mitochondrial DNA (mtDNA) is critically dependent upon
      polymerase-gamma (pol-gamma), encoded by the nuclear gene POLG. Over the last 5
      years, it has become clear that mutations of POLG are a major cause of human
      disease. Secondary mtDNA defects characterize these disorders, with mtDNA
      depletion, multiple mtDNA deletions or multiple point mutations of mtDNA in
      clinically affected tissues. The secondary mtDNA defects cause cell and tissue
      specific deficiencies of mitochondrial oxidative phosphorylation, leading to
      organ dysfunction and human disease. Functional genetic variants of POLG are
      present in up to approximately 0.5% of the general population, and pathogenic
      mutations have been described in most exons of the gene. Clinically, POLG
      mutations can present from early neonatal life to late middle age, with a
      spectrum of phenotypes that includes common neurological disorders such as
      migraine, epilepsy and Parkinsonism. Transgenic mice and biochemical studies of
      recombinant mutated proteins are helping to unravel mechanisms of pathogenesis,
      and patterns are beginning to emerge relating genotype to phenotype.

PMID- 16987891
TI  - Challenges and opportunities in dystrophin-deficient cardiomyopathy gene therapy.
AB  - The last decade has evidenced unprecedented progress in gene therapy of Duchenne
      and Becker muscular dystrophy (DMD and BMD) skeletal muscle disease.
      Cardiomyopathy is a leading cause of morbidity and mortality in both patients and
      carriers of DMD, BMD and X-linked dilated cardiomyopathy. However, there is
      little advance in heart gene therapy. The gene, the vector, vector delivery, the
      target tissue and animal models are five fundamental components in developing an
      effective gene therapy. Intensive effort has been made in optimizing gene
      transfer vectors and methods. Systemic and/or local delivery of recombinant adeno
      associated viral vector have resulted in widespread transduction in the rodent
      heart. The current challenge is to define other parameters that are essential for
      a successful gene therapy such as the best candidate gene(s), the optimal
      expression level and the target tissue. This review focuses on these long-ignored
      aspects and points out future research directions. In particular, we need to
      address whether all or only some of the recently developed mini- and microgenes
      are protective in the heart, whether partial correction can lead to whole heart
      function improvement, whether over-expression is hazardous and whether correcting
      skeletal muscle disease can slow down or stop the progression of cardiomyopathy.
      Discussion is also made on whether the current mouse models can meet these
      research needs.

PMID- 16987892
TI  - Usher syndrome: molecular links of pathogenesis, proteins and pathways.
AB  - Usher syndrome is the most common form of deaf-blindness. The syndrome is both
      clinically and genetically heterogeneous, and to date, eight causative genes have
      been identified. The proteins encoded by these genes are part of a dynamic
      protein complex that is present in hair cells of the inner ear and in
      photoreceptor cells of the retina. The localization of the Usher proteins and the
      phenotype in animal models indicate that the Usher protein complex is essential
      in the morphogenesis of the stereocilia bundle in hair cells and in the calycal
      processes of photoreceptor cells. In addition, the Usher proteins are important
      in the synaptic processes of both cell types. The association of other proteins
      with the complex indicates functional links to a number of basic cell-biological
      processes. Prominently present is the connection to the dynamics of the actin
      cytoskeleton, involved in cellular morphology, cell polarity and cell-cell
      interactions. The Usher protein complex can also be linked to the
      cadherins/catenins in the adherens junction-associated protein complexes,
      suggesting a role in cell polarity and tissue organization. A third link can be
      established to the integrin transmembrane signaling network. The Usher
      interactome, as outlined in this review, participates in pathways common in inner
      ear and retina that are disrupted in the Usher syndrome.

PMID- 16987893
TI  - Molecular components of the mammalian circadian clock.
AB  - Circadian rhythms are approximately 24-h oscillations in behavior and physiology,
      which are internally generated and function to anticipate the environmental
      changes associated with the solar day. A conserved transcriptional-translational
      autoregulatory loop generates molecular oscillations of 'clock genes' at the
      cellular level. In mammals, the circadian system is organized in a hierarchical
      manner, in which a master pacemaker in the suprachiasmatic nucleus (SCN)
      regulates downstream oscillators in peripheral tissues. Recent findings have
      revealed that the clock is cell-autonomous and self-sustained not only in a
      central pacemaker, the SCN, but also in peripheral tissues and in dissociated
      cultured cells. It is becoming evident that specific contribution of each clock
      component and interactions among the components vary in a tissue-specific manner.
      Here, we review the general mechanisms of the circadian clockwork, describe
      recent findings that elucidate tissue-specific expression patterns of the clock
      genes and address the importance of circadian regulation in peripheral tissues
      for an organism's overall well-being.

PMID- 16987894
TI  - Ultrastructural evaluation of explanted opacified Hydroview (H60M) intraocular
      lenses.
AB  - AIM: To describe the ultrastructural appearance of explanted opacified Hydroview
      H60M intraocular lenses. METHODS: 14 explanted lenses were examined by scanning
      electron microscopy, and their appearance compared with a non-implanted H60M lens
      from the same time period. Wavelength-dispersive x ray spectroscopy (WDX) was
      performed on two opacified lenses. RESULTS: Subsurface deposits were seen in all
      explanted opacified lenses. These deposits broke only onto the surface of more
      densely opacified lenses. WDX confirmed that the deposits contained both calcium
      and phosphorous, consistent with their being calcium apatite. CONCLUSION: These
      findings challenge the widely accepted opinion that H60M intraocular lens
      opacification begins on the surface of the optic.

PMID- 16987895
TI  - Effect of verteporfin photodynamic therapy on endostatin and angiogenesis in
      human choroidal neovascular membranes.
AB  - AIM: To evaluate the effect of verteporfin photodynamic therapy (PDT) on
      endostatin with regard to expression of vascular endothelial growth factor (VEGF)
      in human choroidal neovascular membranes (CNVs) secondary to age-related macular
      degeneration. METHODS: A retrospective review of an interventional case series of
      68 patients who underwent removal of CNV. 29 patients were treated with PDT 3-655
      days before surgery. 39 CNVs without previous treatment were used as controls.
      CNVs were stained for CD34, CD105, Ki-67, cytokeratin 18, endostatin, E-selectin
      and VEGF. "Predominance score of VEGF over endostatin" (mean) was defined as the
      difference between VEGF and endostatin staining scores. RESULTS: In four CNVs
      treated by PDT 3 days previously, PS was significantly higher in the retinal
      pigment epithelium (mean = 2.5, p = 0.006) and stroma (mean = 2, p = 0.015) than
      in the control group (mean = 0). At longer post-PDT intervals, PS was
      significantly decreased in the retinal pigment epithelium (mean = 0, p = 0.019)
      and stroma (mean = 0, p = 0.015). Proliferative activity was high (p = 0.023),
      but mostly related to inflammatory cells. PDT did not influence E-selectin
      expression significantly. CONCLUSIONS: VEGF predominance over endostatin early
      after PDT might contribute to enhanced angiogenic activity associated with
      recurrences. Strategies upregulating or replacing endostatin early after PDT
      might increase the effectiveness of PDT.

PMID- 16987896
TI  - Urrets-Zavalia syndrome as a complication of argon laser peripheral iridoplasty.
AB  - OBJECTIVE: To report on 8 patients who developed prolonged mydriasis after argon
      laser peripheral iridoplasty (ALPI). DESIGN: Retrospective case series. METHODS:
      A review of the charts of 8 patients with persistent occludable angles after
      laser iridotomy who developed mydriasis after undergoing ALPI. RESULTS: 12 eyes
      of 8 patients (mean age 50.2, standard deviation 6.9, range 40-61 years)
      developed persistent dilatation. 7 of 8 patients had plateau iris syndrome. Only
      one patient had a decrease in visual acuity. Intraocular pressure increased only
      in 1 eye and remained stable or decreased in the others. Of the 8 patients, 7 had
      blurred vision, 2 had photophobia, 4 had glare and 1 had discomfort. The
      pupillary response to pilocarpine instillation was minimal or absent. Mydriasis
      eventually resolved in all eyes without treatment. CONCLUSION: ALPI can be
      complicated by mydriasis unresponsive to pilocarpine. Mydriasis and accompanying
      symptoms resolved spontaneously within 1 year in most patients.

PMID- 16987897
TI  - Cultured human ocular surface epithelium on therapeutic contact lenses.
AB  - BACKGROUND: This study was initiated after observation of some intriguing
      epithelial growth properties of contact lenses used as a bandage for patients
      after pterygium surgery. AIM: To determine the efficacy of culturing human ocular
      surface epithelial cells on therapeutic contact lenses in autologous serum with a
      view of using this system to transfer epithelial cells to patients with
      persistent corneal or limbal defects. METHODS: Excess graft tissue resected from
      patients undergoing pterygium surgery (n = 3) consisting of limbal epithelium was
      placed on siloxane-hydrogel contact lenses (lotrafilcon A and balafilcon A).
      Limbal explants were cultured in media with 10% autologous serum. Morphology,
      proliferative capacity and cytokeratin profile were determined by phase contrast,
      light and electron microscopy, and immunohistochemical analysis. RESULTS:
      Lotrafilcon A contact lenses sustained proliferation and migration from limbal
      tissue. Cells became confluent after 10-14 days and consisted of 2-3 layers with
      a corneal phenotype (CK3(+)/CK12(+)/CK19(-)) and a propensity to proliferate
      (p63(+)). Electron microscopy showed microvilli on the apical surface with
      adhesive projections, indicating that these cells were stable and likely to
      survive for a long term. Growth was not observed from limbal explants cultured on
      balafilcon A contact lenses. CONCLUSION: A method for culturing human ocular
      surface epithelium on contact lenses that may facilitate expansion and transfer
      of autologous limbal epithelial cells while avoiding the risks associated with
      transplanting allogeneic tissue has been developed. This technique may be
      potentially useful for the treatment of patients with limbal stem cell
      deficiency.

PMID- 16987898
TI  - Combined photodynamic therapy and intravitreal triamcinolone injection for the
      treatment of choroidal neovascularisation secondary to pathological myopia: a
      pilot study.
AB  - BACKGROUND: To assess the efficacy and safety of combined intravitreal
      triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the
      treatment of choroidal neovascularisation (CNV) secondary to pathological myopia.
      METHODS: 22 eyes of 22 patients with subfoveal or juxtafoveal CNV due to
      pathological myopia were prospectively recruited for combined PDT with IVTA. The
      treatment outcomes at 1 year were compared with those in a control group of 22
      eyes that received PDT monotherapy. RESULTS: At 1 year, the logMAR best-corrected
      visual acuity (BCVA) for the combined PDT with IVTA group changed from 0.62 to
      0.61 (p = 0.74), whereas that for the monotherapy group changed from 0.61 to 0.67
      (p = 0.33). The mean logMAR BCVA and proportions of patients without losing > or
      =3 lines at 1 year were similar between the two groups (p = 0.68 and 0.74,
      respectively). Subgroup analyses showed that eyes with baseline logMAR BCVA worse
      than 0.6 (Snellen equivalent 20/80) or CNV with greatest linear dimension > or
      =750 microm which received combined therapy had better mean logMAR BCVA at 1 year
      (p = 0.023 and 0.041, respectively), with a higher proportion of eyes gaining >
      or =2 lines of BCVA (p = 0.027 and 0.017, respectively) compared with PDT
      monotherapy. CONCLUSIONS: Combined PDT with IVTA did not seem to result in
      significantly better visual outcome compared with PDT monotherapy. However,
      combined therapy might result in better visual outcome in selected patients with
      worse initial visual acuity or larger myopic CNV. Further studies are warranted
      to investigate the role of combined PDT with IVTA in the treatment of myopic CNV,
      especially in patients with worse prognostic factors.

PMID- 16987899
TI  - Comparison of acute structural and histopathological changes in human autopsy
      eyes after endoscopic cyclophotocoagulation and trans-scleral
      cyclophotocoagulation.
AB  - AIM: To study the histological effects of trans-scleral cyclophotocoagulation
      (TCP) and endoscopic cyclophotocoagulation (ECP) on the ciliary body and other
      structures collected at autopsy and to compare with untreated controls. MATERIALS
      AND METHODS: TCP and ECP were performed on human eyes at autopsy. Detailed
      histological evaluations were perfomed using light microscopy and scanning
      electron microscopy on treated eyes and compared with untreated controls.
      RESULTS: Histological changes were observed with both light microscopy and
      scanning electron microscopy for all treated tissues. Tissue treated with TCP
      showed pronounced tissue disruption of the ciliary body muscle and stroma,
      ciliary processes, and both pigmented and non-pigmented ciliary epithelium. ECP
      treated tissue exhibited pronounced contraction of the ciliary processes with
      disruption of the ciliary body epithelium, sparing of the ciliary body muscle and
      less architectural disorganisation. The sclera was not affected by either laser
      treatment. CONCLUSIONS: ECP treatment caused less damage to the ciliary body
      compared with TCP when evaluated by light microscopy and scanning electron
      microscopy. Compared with TCP, ECP seems to be a more selective form of
      cyclophotocoagulation, resulting in less tissue disruption while achieving the
      goal of destroying ciliary body epithelium.

PMID- 16987900
TI  - Histological evidence for revascularisation of an autologous retinal pigment
      epithelium--choroid graft in the pig.
AB  - BACKGROUND: Translocation of a free autologous graft consisting of retinal
      pigment epithelium (RPE), Bruch's membrane, choriocapillaris and choroid in
      patients with exudative age-related macular degeneration is currently being
      evaluated in clinical practice. Angiographic studies in these patients suggest
      that their grafts become revascularised. AIM: To investigate the histological
      evidence of revascularisation of the graft in a porcine model. METHODS: In 11
      pigs (11 eyes), an RPE-choroid graft was translocated from the mid-periphery to
      an intact or an intentionally damaged RPE and Bruch's membrane at the recipient
      site. The eyes were enucleated 1 week or 3 months after surgery. Tissue sections
      were evaluated using immunohistochemistry. RESULTS: Bridging vessels between
      recipient layer and graft were identified from 1 week to 3 months after surgery.
      This reconnection occurred regardless of whether the Bruch's membrane of the
      recipient site was left intact or intentionally damaged at the time of
      transplantation. The vasculature of the graft appeared open and perfused. Vessels
      with transcapillary pillars and conglomerates of small new vessels were present
      in the graft. CONCLUSIONS: This study showed histological evidence for
      revascularisation by angiogenesis of a free autologous RPE-choroid graft.

PMID- 16987901
TI  - Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental
      autoimmune uveoretinitis in Rats.
AB  - AIM: To determine whether intravitreal injection of tacrolimus suppresses ongoing
      experimental autoimmune uveoretinitis (EAU) in rats. METHODS: Rats were immunised
      with interphotoreceptor retinoid-binding protein peptide (R14) and given an
      intravitreal injection of tacrolimus on day 12 after immunisation. Intraocular
      inflammation was assessed by slit-lamp biomicroscopy and histopathological
      examination. Interferon gamma and tumour necrosis factor alpha protein levels in
      the ocular tissues were measured. Gene expression of chemokines was determined in
      ocular tissues by reverse transcription-polymerase chain reaction. To evaluate
      the systemic effect of intravitreal injection of tacrolimus, delayed-type
      hypersensitivity was measured by ear swelling. RESULTS: Clinical and pathological
      scores showed that ocular inflammation of tacrolimus-treated eyes was markedly
      less than that of vehicle-treated eyes. The amount of interferon gamma and tumour
      necrosis factor alpha was considerably inhibited in tacrolimus-treated eyes. The
      gene expression of monocyte chemattractant protein-1 (MCP-1) and regulated upon
      activation, normal T cell expressed and secreted (RANTES) was markedly reduced in
      tacrolimus-treated eyes. Delayed-type hypersensitivity responses were not
      impaired in tacrolimus-treated rats. CONCLUSIONS: Intravitreal injection of
      tacrolimus was highly effective in suppressing the ongoing process of EAU without
      any side effects on systemic cellular immunity. This treatment may be useful in
      the management of patients with severe uveitis.

PMID- 16987902
TI  - Axial length and optic disc size in normal eyes.
AB  - AIM: To investigate the relationship between optic disc area and axial length in
      normal eyes of white and black people. METHODS: Consecutive eligible normal
      subjects were enrolled. Ocular biometry was obtained using A-scan
      ultrasonography, and reliable images of the optic disc were obtained using a
      confocal scanning laser ophthalmoscope. The relationship between optic disc area
      and axial length was assessed using univariate and multivariate models. RESULTS:
      281 eyes of 281 subjects were enrolled. Black subjects (n = 157) had
      significantly larger discs (mean (SD) disc area, 2.12 (0.5) mm(2)) than white
      subjects (n = 124; 1.97 (0.6) mm(2); t test, p = 0.02). Optic disc area increased
      with axial length (Pearson's correlation coefficient, r = 0.13, p<0.035) for the
      entire study population. Multivariate regression models including race, disc area
      and axial length showed that a significant but weak linear relationship exists
      between axial length and disc area (partial correlation coefficient 0.14;
      p<0.024), and with race and disc area (partial correlation coefficient 0.19;
      p<0.017) when adjusted for the effects of other terms in the model. CONCLUSION:
      Increased disc area is associated with longer axial length measurements and
      African ancestry. This may have implications for pathophysiology and risk
      assessment of glaucoma.

PMID- 16987903
TI  - Histological parameters helpful in recognising steroid-treated temporal
      arteritis: an analysis of 35 cases.
AB  - AIM: To establish the histological and immunohistochemical parameters that are
      helpful in recognising temporal arteritis in patients who have been treated with
      steroids before biopsy, and to analyse the clinical features and correlate them
      with the histological findings. METHODS: A retrospective review of charts of 35
      patients treated with steroids before obtaining temporal artery biopsy specimens,
      spanning a 11-year period from 1995 to 2005. The study was conducted at the
      Ophthalmic Pathology Laboratory, Cullen Eye Institute, Houston, Texas, USA. The
      clinical features were evaluated and correlated with the histopathological
      findings. Each case was evaluated with respect to age, sex, race, clinical
      findings, erythrocyte sedimentation rate, corticosteroid dosage (oral versus
      intravenous) and the duration of treatment. The time interval between obtaining
      the biopsy specimen and the onset of steroid treatment was carefully recorded for
      each patient. In selected cases, histiocytic markers (CD-68 and HAM-56) were used
      to identify the presence of epithelioid histiocytes, which characterises a
      granulomatous inflammation. Other immunohistochemical studies (CD3, CD20, CD4,
      CD8, CD45RO, CD45RA and S-100 protein) were performed in selected cases to
      characterise the inflammatory cells. RESULTS: The three most reliable
      histopathological parameters of corticosteroid-treated temporal arteritis are the
      following: (1) complete or incomplete mantle of lymphocytes and epithelioid
      histiocytes located between the outer muscular layer and the adventitia; (2)
      large circumferential defects in the elastic lamina (best seen with the Movat's
      pentachrome); and (3) absent or few small multinucleated giant cells. In some
      cases the main artery appears normal, whereas the primary branches show evidence
      of a healing arteritis. The histological findings vary according to the duration
      of treatment before obtaining the biopsy specimen. CONCLUSION: Striking
      histological differences can be recognised objectively between patients with
      active (untreated) giant cell arteritis and patients who have been treated with
      corticosteroids. The earliest histopathological changes were detected by the end
      of the first week after steroid treatment (usually after day 4 to the end of the
      first week). The histological findings were more difficult to recognise at 2-3
      months after steroid treatment. Ophthalmic and general pathologists should be
      able to recognise this entity on the basis of the histological findings including
      the special stains and results of immunohistochemical studies (CD-68 and HAM-56).

PMID- 16987904
TI  - Visual function in human ocular toxoplasmosis.
AB  - AIM: To assess functional impairment in terms of visual acuity reduction and
      visual field defects in inactive ocular toxoplasmosis. METHODS: 61 patients with
      known ocular toxoplasmosis in a quiescent state were included in this
      prospective, cross-sectional study. A complete ophthalmic examination, retinal
      photodocumentation and standard automated perimetry (Octopus perimeter, program
      G2) were performed. Visual acuity was classified on the basis of the World Health
      Organization definition of visual impairment and blindness: normal (> or =20/25),
      mild (20/25 to 20/60), moderate (20/60 to 20/400) and severe (<20/400). Visual
      field damage was correspondingly graded as mild (mean defect <4 dB), moderate
      (mean defect 4-12 dB) or severe (mean defect >12 dB). RESULTS: 8 (13%) patients
      presented with bilateral ocular toxoplasmosis. Thus, a total of 69 eyes was
      evaluated. Visual field damage was encountered in 65 (94%) eyes, whereas only 28
      (41%) eyes had reduced visual acuity, showing perimetric findings to be more
      sensitive in detecting chorioretinal damage (p<0.001). Correlation with the
      clinical localisation of chorioretinal scars was better for visual field (in 70%
      of the instances) than for visual acuity (33%). Moderate to severe functional
      impairment was registered in 65.2% for visual field, and in 27.5% for visual
      acuity. CONCLUSION: In its quiescent stage, ocular toxoplasmosis was associated
      with permanent visual field defects in >94% of the eyes studied. Hence, standard
      automated perimetry may better reflect the functional damage encountered by
      ocular toxoplasmosis than visual acuity.

PMID- 16987905
TI  - Triamcinolone acetonide suppresses early proangiogenic response in retinal
      pigment epithelial cells after photodynamic therapy in vitro.
AB  - OBJECTIVE: To investigate the expression of proangiogenic and antiangiogenic
      factors, vascular endothelial growth factor (VEGF) and pigment epithelium-derived
      factor (PEDF) in retinal pigment epithelial (RPE) cells after photodynamic
      therapy (PDT), especially focusing on their change in the presence of
      triamcinolone acetonide. METHODS: Firstly, the cellular uptake of verteporfin was
      quantified after confluent ARPE-19 (human retinal pigment epithelial) cells were
      exposed to 5 microg/ml verteporfin combined with or without 1 microg/ml
      triamcinolone acetonide for 1 h. Secondly, ARPE-19 cells exposed to various doses
      of verteporfin were irradiated with 120 mJ/cm(2) light. After incubation with or
      without 1 microg/ml triamcinolone acetonide for 2 days, cell viability and
      expressions of VEGF and PEDF were assessed. RESULTS: Cellular uptake of
      verteporfin was not significantly changed by the presence of 1 microg/ml
      triamcinolone acetonide. In addition, 0.01-0.1 microg/ml of verteporfin showed a
      dose-dependent toxicity on the ARPE-19 cells 2 days after the light exposure. The
      presence of verteporfin at a concentration of 0.01 microg/ml did not affect the
      cell viability but significantly increased VEGF (p<0.001) and reduced PEDF (p =
      0.03) expression. Administration of triamcinolone acetonide significantly
      suppressed both this increase in VEGF (p<0.001) and decrease in PEDF (p = 0.001).
      CONCLUSIONS: VEGF was increased and PEDF reduced in cultured RPE cells shortly
      after PDT even at a sublethal dose. Triamcinolone acetonide suppressed this
      proangiogenic response.

PMID- 16987906
TI  - ACC/AHA/ESC 2006 guidelines for the management of patients with atrial
      fibrillation: full text: a report of the American College of Cardiology/American
      Heart Association Task Force on practice guidelines and the European Society of
      Cardiology Committee for Practice Guidelines (Writing Committee to Revise the
      2001 guidelines for the management of patients with atrial fibrillation)
      developed in collaboration with the European Heart Rhythm Association and the
      Heart Rhythm Society.

PMID- 16987907
TI  - Using RNA secondary structures to guide sequence motif finding towards single
      stranded regions.
AB  - RNA binding proteins recognize RNA targets in a sequence specific manner. Apart
      from the sequence, the secondary structure context of the binding site also
      affects the binding affinity. Binding sites are often located in single-stranded
      RNA regions and it was shown that the sequestration of a binding motif in a
      double-strand abolishes protein binding. Thus, it is desirable to include
      knowledge about RNA secondary structures when searching for the binding motif of
      a protein. We present the approach MEMERIS for searching sequence motifs in a set
      of RNA sequences and simultaneously integrating information about secondary
      structures. To abstract from specific structural elements, we precompute position
      specific values measuring the single-strandedness of all substrings of an RNA
      sequence. These values are used as prior knowledge about the motif starts to
      guide the motif search. Extensive tests with artificial and biological data
      demonstrate that MEMERIS is able to identify motifs in single-stranded regions
      even if a stronger motif located in double-strand parts exists. The discovered
      motif occurrences in biological datasets mostly coincide with known protein
      binding sites. This algorithm can be used for finding the binding motif of single
      stranded RNA-binding proteins in SELEX or other biological sequence data.

PMID- 16987908
TI  - Once-weekly epoetin-beta improves hemoglobin levels in cancer patients with
      chemotherapy-induced anemia: A randomized, double-blind, dose-finding study.
AB  - OBJECTIVE: To determine a recommended dose of once-weekly epoetin-beta
      administration for anemic cancer patients receiving myelosuppressive
      chemotherapy, we conducted a multicenter, randomized, double-blind trial.
      METHODS: A total of 86 patients with malignant lymphoma or lung cancer who
      received chemotherapy containing platinum, taxanes or anthracyclines were
      enrolled in the study. Patients were randomly assigned into groups that received
      three dose levels of epoetin-beta (9000, 18,000 or 36,000 IU) administered
      subcutaneously once a week for 12 weeks. The primary endpoint was change in
      hemoglobin, while the secondary endpoints were quality of life (QOL) assessed by
      Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire and
      transfusion requirements. RESULTS: Among the 69 patients (per protocol set
      population) assessable for efficacy, hemoglobin level change in the 36,000 IU
      group was significantly greater than that in the 9000 IU group (1.75 +/- 2.15
      versus 0.04 +/- 1.98 g/dl; P = 0.009), and a significant dose-response
      relationship was observed for the change in hemoglobin level (P = 0.003).
      Although changes in FACT-An Total Fatigue subscale (Fatigue subscale) scores were
      similar for the three dosage groups, there was a statistically significant
      correlation (r = 0.435, P < 0.001) between the change in hemoglobin levels and
      the change in Fatigue subscale scores. The proportion of transfused patients was
      significantly smaller in the 36 000 IU group compared with that in the 9000 IU
      group (P = 0.022, not adjusted for pre-study transfusions). The incidence of
      adverse events was similar in the three dosage groups. CONCLUSIONS: Once-weekly
      epoetin-beta 36,000 IU for 12 weeks was well tolerated and significantly
      increased hemoglobin levels in anemic cancer patients receiving chemotherapy.

PMID- 16987909
TI  - Thick target neutron dose evaluation for 19F+Al system.
AB  - Measured angular distribution of neutron dose from 110 MeV (19)F projectiles
      bombarding a thick aluminium target is reported. The measurements are carried out
      with a commercially available rem meter at 0 degrees, 30 degrees, 60 degrees and
      90 degrees. The experimental results are compared with calculated dose from
      different empirical formulations proposed by earlier workers as well as with
      calculated dose from theoretically estimated energy distributions from the
      nuclear reaction model code EMPIRE-2.18.

PMID- 16987910
TI  - Dosimetric monitoring in Ukraine--present status and path to the future.
AB  - Despite wide use of nuclear energy and radiation sources in industry and
      medicine, there is no centralised dose accounting system in Ukraine; existing
      dosimetry services operate obsolete manual thermoluminescence dosemeter (TLD)
      readers and do not meet modern proficiency standards. Currently, dosimetric
      monitoring is required for approximately 42,000 occupationally exposed workers,
      including 9100 in medicine, 17,000 employees of nuclear power plants and
      approximately 16,000 workers dealing with other sources of occupational exposure.
      This article presents the plan of elaboration of the United System for monitoring
      and registration of individual doses which has the aim of harmonisation of
      individual monitoring in Ukraine through securing methodical unity; scientific
      and methodological guidance of individual dosimetric control; procurement of
      common technical policy regarding nomenclature and operation of instrumentation;
      implementation of quality assurance programmes; development and support of
      information infrastructure, in particular operation of the national registry of
      individual doses; training and certification of personnel engaged in the system
      of individual dosimetric monitoring.

PMID- 16987911
TI  - Modelling and analyses do not support the hypothesis that charging by power-line
      corona increases lung deposition of airborne particles.
AB  - The National Radiological Protection Board's advisory Group on Non-ionising
      Radiation has recommended further study on the effects of electric charge on the
      deposition of 0.005-1 microm particles in the lung. Estimates have been made
      regarding the integrated ion exposure within the corona plume generated by a
      power line and by ionisers in an intensive care unit. Changes in the charge state
      of particles with sizes in the range 0.02-13 mum have been calculated for these
      exposures. The corona plume increases the charge per particle of 0.02 and 0.1
      microm particles by the order of 0.1. The ionisers in the intensive care unit
      produced negative ions-as do power lines under most conditions. Bacteria can
      carry in the order of 1000 charges (of either sign) and it is shown that the
      repulsion between such a negatively charged bacterium and negative ions prevents
      further ion deposition by diffusion charging. Positively charged bacteria can,
      however, be discharged by the ions which are attracted to them. The data provide
      no support for the hypothesis that ion exposure, at the levels considered, can
      increase deposition in the lung.

PMID- 16987912
TI  - Official dosimetry with personal electronic dosemeters--the framework in Germany.
AB  - In Germany, personal electronic dosemeters (AEPDs) are presently applied mainly
      for operational radiation protection monitoring particularly in nuclear power
      engineering companies, large hospitals and research centres. This is done in
      addition to the official dosimetry of record. Therefore, frequently, double
      monitoring occurs-officially and operationally. A crucial advantage of AEPDs
      compared with passive dosemeters is the ability to adapt the monitoring period to
      the working time in controlled areas and to allow an immediate readout of the
      dose after leaving the controlled area, e.g. a job-related monitoring is possible
      by correlating the readout dose with the job performed. Germany started a general
      research project, consisting of two parts, for an optimised implementation of
      personal electronic dosemeters into official dosimetry. The use of AEPDs as
      official dosemeters depends on an approval by Federal and Federal State
      ('Lander') authorities as an official dosimetry system, which has to comply with
      special requirements ensuring that the legal requirements are fulfilled. The
      formulation of these special requirements is in the focus of part one of the
      research project, supervised by the Federal Office for Radiation Protection (BfS)
      and performed by the Gesellschaft fur Anlagen- und Reaktorsicherheit (GRS) mbH.
      As a result of part one, a framework was developed which is the basis for a
      future technical implementation project. Part one is described in the paper,
      while part two is still to be initiated and will deal with the implementation and
      testing phase of the introduction of personal electronic dosemeters as official
      dosemeters.

PMID- 16987913
TI  - Doses to nuclear technicians in a dedicated PET/CT centre utilising 18F
      fluorodeoxyglucose (FDG).
AB  - The first dedicated PET/CT centre in Norway was established at the Norwegian
      Radiumhospital in Oslo in 2005. Knowing that the introductions of PET-isotopes in
      nuclear medicine give increased occupational radiation dose to the technicians, a
      study was carried out in order to map the doses to staff members during different
      working operations and to see if any dose reducing measures were needed. The
      results of the study are in good agreement with other studies, and a technician
      dose of 20-25 nSv per injected MBq of 18F seems to be representative for such
      centres. For an average injected activity of 350 MBq per patient, the dose limit
      is reached after handling around 3000 patients annually. For an annual number of
      less than 500 patients at the centre and rotation of the staff, an annual
      individual dose for the technicians would realistically be less than 2-3 mSv.
      Even a major increase in the number of patients will not result in individual
      doses near the ICRP dose limit.

PMID- 16987915
TI  - On the assessment of the performance of personal dosemeters and individual
      monitoring services.
AB  - Based on recommendations of the International Commission on Radiological
      Protection, recommendations and requirements on the performance of dosimetric
      systems and individual monitoring services have been formulated in national and
      international standards and other documents of relevance. Although these all have
      essentially the same aim, the formulated criteria and the guidance given vary.
      Using the individual monitoring service of NRG in Arnhem and its
      thermoluminescence dosemeter as an example, the current paper reviews a number of
      ways to estimate the uncertainty in dose assessments and compares the criteria
      given in recommendations and standards. An attempt is made to contribute to some
      convergence of recommendations and requirements on aspects of dosimetric
      performance.

PMID- 16987914
TI  - New developments in radiochromic film dosimetry.
AB  - NIST has been a pioneer in the use of radiochromic film for medical dosimetry
      applications. Beginning in 1988 with experiments with (90)Sr/Y ophthalmic
      applicators, this work has continued into the present. A review of the latest
      applications is presented, which include high activity low-energy photon source
      dosimetry and ultra-high resolution film densitometry for dose enhancement near
      stents and microbeam radiation therapy dosimetry. An exciting recent development
      is the availability of a new radiochromic emulsion which has been developed for
      IMRT dosimetry. This emulsion is an order of magnitude more sensitive than was
      previously available. Measurements of the sensitivity and uniformity of samples
      of this new film are reported, using a spectrophotometer and two scanning laser
      densitometers. A unique feature of the new emulsion is that the peak of the
      absorbance spectrum falls at the wavelength of the HeNe lasers used in the
      densitometer, maximising sensitivity. When read at a wavelength of 633 nm,
      sensitivities on the order of 900 mAU Gy(-1) were determined for this new film
      type, compared with about 40 mAU Gy(-1) for type HS film, 20 mAU Gy(-1) for type
      MD-55-2 film, and 3 mAU Gy(-1) for type HD-810. Film uniformities were found to
      be good, on the order of 6% peak to peak. However, there is a strong polarisation
      effect in the samples examined, requiring care in film orientation during
      readout.

PMID- 16987916
TI  - Long-term stability of a TLD-based individual monitoring system.
AB  - The thermoluminescence dosemeter (TLD) system at the Individual Monitoring
      Service (IMS) of the Nuclear Technology Institute (ITN) at the Radiological
      Protection and Nuclear Safety Department (DPRSN) comprises two 6600 Harshaw
      readers and the Harshaw 8814 TL card and the holder containing two LiF:Mg,Ti (TLD
      100) dosemeters for the evaluation of H(p)(10) and H(p)(0.07). The readers are
      calibrated on a monthly basis and as part of the quality assurance programme
      implemented at the IMS a set of dosemeters is issued monthly to the DPRSN's
      Standard Dosimetry Laboratory for linearity measurements. The results obtained
      since November 2001 are presented. Fading and sensitivity change experiments are
      carried out every month covering 8 week periods so that enough time is given to
      simulate issuing, integrating and receiving times and respective delays. A set of
      96 dosemeters organised in eight subsets of 12 are used. In each subset, four
      dosemeters are irradiated and stored at room temperature (RT), four are not
      irradiated at all and the last four are irradiated after storage. The 12
      dosemeters of each subset are readout at the same time, one per week, covering
      the 8 week period. The results from the sets irradiated and stored at different
      periods allowed for the evaluation of fading and sensitivity changes experienced
      over the whole monitoring period and respective preparation time and readout
      delays. Time evolution charts of the reader calibration factors, of the linearity
      parameters and of the evolution of the integrated area in the region of
      dosimetric interest with storage at RT were obtained. This paper aims to quantify
      the long-term stability of the TLD system in use at the IMS.

PMID- 16987917
TI  - Implications of the high voltage induced variation on TL readings.
AB  - The high voltage (HV) induced variation on the thermoluminescence (TL) and on the
      reference light (RL) intensity was investigated in a previous work, which also
      allowed for the definition of warning levels for all the parameters of the
      readers' start up test. Based on the results obtained, a modification of the
      start up procedure was suggested: 'a 10 min warm up time was allowed prior to the
      beginning of the reader's start up tests. The actual and previous HV values
      should differ less than +/-5 V. In case it exceeds, a second test should be
      performed. If the difference exceeds +/-10 V, the voltage should be manually
      adjusted to the previous value and a calibration of the reader is needed. Should
      this occur for more than two successive days, maintenance should be called'. The
      results of the readers' start up tests obtained since the implementation of the
      start up procedure are analysed and the warning levels considered are discussed.
      Charts of the HV-induced variation on the TL and RL readings were obtained,
      compared with the preliminary results and the implications on the start up
      procedure are discussed.

PMID- 16987918
TI  - Some developments in neutron and charged particle dosimetry.
AB  - There is an increasing need for dosimetry of neutrons and charged particles.
      Increasing exposure levels are reported in the nuclear industry, deriving from
      more frequent in-service entries at commercial nuclear power plants, and from
      increased plant decommissioning and refurbishment activities. Another need stems
      from the compliance with requirements of the regulations and standards. The
      European Council directive 96/29 requires dosimetric precautions if the effective
      dose exceeds 1 mSv a(-1). On average, aircrew members exceed this value. Further,
      there is a trend of increasing use of charged particles in radiotherapy. The
      present situation is that we have reasonably good photon dosemeters, but neutron
      and charged particle dosemeters are still in need of improvements. This work
      highlights some of the developments in this field. It is mainly concentrated on
      some developments in passive dosimetry, in particular thermally and optically
      stimulated luminescent detectors, indicating the direction of ongoing research.
      It shows that passive dosemeters are still a very active field. Active dosemeters
      will not be discussed with the exception of new developments in microdosimetric
      measurements [new types of tissue equivalent proportional counters (TEPCs)]. The
      TEPC is unique in its ability to provide a simultaneous determination of neutron
      / charged particle / gamma ray doses, or dose equivalents using a single
      detector.

PMID- 16987919
TI  - Characterisation of bubble detectors for aircrew and space radiation exposure.
AB  - The Earth's atmosphere acts as a natural radiation shield which protects
      terrestrial dwellers from the radiation environment encountered in space. In
      general, the intensity of this radiation field increases with distance from the
      ground owing to a decrease in the amount of atmospheric shielding. Neutrons form
      an important component of the radiation field to which the aircrew and spacecrew
      are exposed. In light of this, the neutron-sensitive bubble detector may be ideal
      as a portable personal dosemeter at jet altitudes and in space. This paper
      describes the ground-based characterisation of the bubble detector and the
      application of the bubble detector for the measurement of aircrew and spacecrew
      radiation exposure.

PMID- 16987920
TI  - Authenticated DNA from ancient wood remains.
AB  - BACKGROUND: The reconstruction of biological processes and human activities
      during the last glacial cycle relies mainly on data from biological remains.
      Highly abundant tissues, such as wood, are candidates for a genetic analysis of
      past populations. While well-authenticated DNA has now been recovered from
      various fossil remains, the final 'proof' is still missing for wood, despite some
      promising studies. SCOPE: The goal of this study was to determine if ancient wood
      can be analysed routinely in studies of archaeology and palaeogenetics. An
      experiment was designed which included blind testing, independent replicates,
      extensive contamination controls and rigorous statistical tests. Ten samples of
      ancient wood from major European forest tree genera were analysed with plastid
      DNA markers. CONCLUSIONS: Authentic DNA was retrieved from wood samples up to
      1,000 years of age. A new tool for real-time vegetation history and archaeology
      is ready to use.

PMID- 16987921
TI  - Small-scale heterogeneity in soil quality influences photosynthetic efficiency
      and habitat selection in a clonal plant.
AB  - BACKGROUND AND AIMS: In clonal plants, internode connections allow translocation
      of photosynthates, water, nutrients and other substances among ramets. Clonal
      plants form large systems that are likely to experience small-scale spatial
      heterogeneity. Physiological and morphological responses of Fragaria vesca to
      small-scale heterogeneity in soil quality were investigated, together with how
      such heterogeneity influences the placement of ramets. As a result of their own
      activities plants may modify the suitability of their habitats over time.
      However, most experiments on habitat selection by clonal plants have not
      generally considered time as an important variable. In the present study, how the
      foraging behaviour of clonal plants may change over time was also investigated.
      METHODS: In a complex of environments with different heterogeneity, plant
      performance was determined in terms of biomass, ramet production and
      photosynthetic activity. To identify habitat selection, the number of ramets
      produced and patch where they rooted were monitored. KEY RESULTS: Parent ramets
      in heterogeneous environments showed significantly higher maximum and effective
      quantum yields of photosystem II than parents in homogeneous environments.
      Parents in heterogeneous environments also showed significantly higher investment
      in photosynthetic biomass and stolon/total biomass, produced longer stolons, and
      had higher mean leaf size than parents in homogeneous environments. Total biomass
      and number of offspring ramets were similar in both environments. However, plants
      in homogeneous environments showed random allocation of offspring ramets to
      surrounding patches, whereas plants in heterogeneous environments showed
      preferential allocation of offspring to higher-quality patches. CONCLUSIONS: The
      results suggest that F. vesca employs physiological and morphological strategies
      to enable efficient resource foraging in heterogeneous environments and
      demonstrate the benefits of physiological integration in terms of photosynthetic
      efficiency. The findings indicate that short-term responses cannot be directly
      extrapolated to the longer term principally because preferential colonization of
      high-quality patches means that these patches eventually show reduced quality.
      This highlights the importance of considering the time factor in experiments
      examining responses of clonal plants to heterogeneity.

PMID- 16987922
TI  - Apoplastic pH during low-oxygen stress in Barley.
AB  - BACKGROUND AND AIMS: Anoxia leads to an energy crisis, tolerance of which varies
      from plant to plant. Although the apoplast represents an important storage and
      reaction space, and engages in the mediation of membrane transport, this
      extracellular compartment has not yet been granted a role during oxygen shortage.
      Here, an attempt is made to highlight the importance of the apoplast during
      oxygen stress and to test whether information about it is transferred
      systemically in Hordeum vulgare. METHODS: Non-invasive ion-selective microprobes
      were used which, after being inserted through open stomata, directly contact the
      apoplastic fluid and continuously measure the apoplastic pH and changes to it.
      KEY RESULTS: (a) Barley leaves respond to oxygen stress with apoplastic
      alkalinization and membrane depolarization. These responses are persistent under
      anoxia (N2; O2 < 3%) but transient under hypoxia. (b) Being applied to the root,
      the information 'anoxia' is signalled to the leaf as an increase in pH, whereas
      'hypoxia' is not: flooding of the roots within the first 2 h has no effect on the
      leaf apoplastic pH, whereas anoxia (N2) or chemical anoxia (NaCN/salicylic
      hydroxamic acid) rapidly increase the leaf apoplastic pH. (c) Under anoxia, the
      proton motive force suffers a decrease by over 70 %, which impairs H(+) -driven
      transport. CONCLUSIONS: Although anoxia-induced apoplastic alkalinization is a
      general response to stress, its impact on the proton motive force (reduction) and
      thus on transport mediation of energy-rich compounds is evident. It is concluded
      that anoxia tolerance depends on how the plant is able to hold the proton motive
      force and H(+) turnover at a level that guarantees sufficient energy is harvested
      to overcome the crisis.

PMID- 16987923
TI  - Association of childhood socioeconomic position with cause-specific mortality in
      a prospective record linkage study of 1,839,384 individuals.
AB  - Previous studies have lacked sufficient power to assess associations between
      early-life socioeconomic position and adult cause-specific mortality. The authors
      examined associations of parental social class at age 0-16 years with mortality
      among 1,824,064 Swedes born in 1944-1960. Females and males from manual compared
      with nonmanual childhood social classes were more likely to die from smoking
      related cancers, stomach cancer, respiratory disease, cardiovascular disease, and
      diabetes. Males from manual compared with nonmanual social classes were more
      likely to die from unintentional injury, homicide, and alcoholic cirrhosis. The
      association with stomach cancer was little affected by adjustment for parental
      later-life and own adult social class or education. For other outcomes,
      educational attainment resulted in greater attenuation of associations than did
      adjustment for adult social class. Early-life social class was not related to
      suicide or to melanoma, colon, breast, brain, or lymphatic cancers or to
      leukemia. With the exception of stomach cancer, caused by Helicobacter pylori
      infection acquired in childhood, poorer social class in early life was associated
      with diseases largely caused by behavioral risk factors such as smoking, physical
      inactivity, and an unhealthy diet. Educational attainment may be important in
      reducing the health inequalities associated with early-life disadvantage.

PMID- 16987924
TI  - Ethanol intake and risk of lung cancer in the European Prospective Investigation
      into Cancer and Nutrition (EPIC).
AB  - Within the European Prospective Investigation into Cancer and Nutrition (EPIC),
      the authors examined the association of ethanol intake at recruitment (1,119
      cases) and mean lifelong ethanol intake (887 cases) with lung cancer. Information
      on baseline and past alcohol consumption, lifetime tobacco smoking, diet, and the
      anthropometric characteristics of 478,590 participants was collected between 1992
      and 2000. Cox proportional hazards regression was used to calculate multivariate
      adjusted hazard ratios and 95% confidence intervals. Overall, neither ethanol
      intake at recruitment nor mean lifelong ethanol intake was significantly
      associated with lung cancer. However, moderate intake (5-14.9 g/day) at
      recruitment (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.63, 0.90)
      and moderate mean lifelong intake (HR = 0.80, 95% CI: 0.66, 0.97) were associated
      with a lower lung cancer risk in comparison with low consumption (0.1-4.9 g/day).
      Compared with low intake, a high (> or =60 g/day) mean lifelong ethanol intake
      tended to be related to a higher risk of lung cancer (HR = 1.29, 95% CI: 0.93,
      1.74), but high intake at recruitment was not. Although there was no overall
      association between ethanol intake and risk of lung cancer, the authors cannot
      rule out a lower risk for moderate consumption and a possibly increased risk for
      high lifelong consumption.

PMID- 16987925
TI  - Balancing competing interests over frozen embryos: the judgment of solomon? Evans
      v. United Kingdom.

PMID- 16987926
TI  - Spectral receptive field properties explain shape selectivity in area V4.
AB  - Neurons in cortical area V4 respond selectively to complex visual patterns such
      as curved contours and non-Cartesian gratings. Most previous experiments in V4
      have measured responses to small, idiosyncratic stimulus sets and no single
      functional model yet accounts for all of the disparate results. We propose that
      one model, the spectral receptive field (SRF), can explain many observations of
      selectivity in V4. The SRF describes tuning in terms of the orientation and
      spatial frequency spectrum and can, in principle, predict the response to any
      visual stimulus. We estimated SRFs for neurons in V4 of awake primates by
      linearized reverse correlation of responses to a large set of natural images. We
      find that V4 neurons have large orientation and spatial frequency bandwidth and
      often bimodal orientation tuning. For comparison, we estimated SRFs for neurons
      in primary visual cortex (V1). Consistent with previous observations, we find
      that V1 neurons have narrower bandwidth than that of V4. To determine whether
      estimated SRFs can account for previous observations of selectivity, we used them
      to predict responses to Cartesian gratings, non-Cartesian gratings, natural
      images, and curved contours. Based on these predictions, we find that the
      majority of neurons in V1 are selective for Cartesian gratings, whereas the
      majority of V4 neurons are selective for non-Cartesian gratings or natural
      images. The SRF describes visual tuning properties with a second-order nonlinear
      model. These results support the hypothesis that a second-order model is
      sufficient to describe the general mechanisms mediating shape selectivity in area
      V4.

PMID- 16987927
TI  - Acute injury to superficial cortex leads to a decrease in synaptic inhibition and
      increase in excitation in neocortical layer V pyramidal cells.
AB  - Injury to the superficial layers of cerebral cortex produces alterations in the
      synaptic responses of local circuits that promote the development of seizures. To
      further delineate the specific changes in synaptic strength that are induced by
      this type of cortical injury, whole cell voltage-clamp recordings were used to
      examine evoked and spontaneous synaptic events from layer V pyramidal cells in
      coronal slices prepared from surgically traumatized rat neocortices in which the
      superficial third of the cortex (layers I, II, and part of III) was removed.
      Slices from intact neocortices were used as controls. Examinations of fast
      inhibitory postsynaptic currents (IPSCs) indicated that traumatized slices were
      disinhibited, exhibiting evoked IPSCs (eIPSCs) with lower peak amplitudes.
      Measurements of spontaneous IPSCs (sIPSCs) revealed no difference in the mean
      amplitudes of sIPSCs recorded in traumatized versus control slices. However, the
      mean sIPSC frequency was lower in traumatized slices, indicative of a decrease in
      GABA release at these inhibitory synapses. Traumatized slices also displayed an
      increase in synaptic excitation, exhibiting spontaneous EPSCs (sESPCs) with
      larger peak amplitudes and higher frequencies. Peak-scaled nonstationary
      fluctuation analysis of sEPSCs and sIPSCs was used to obtain estimates of the
      unit conductance and number of functional receptor channels. EPSC and IPSC
      channel numbers and IPSC unit conductance did not differ between traumatized and
      intact slices. However, the mean unit conductance of EPSCs was higher (+25%) in
      traumatized slices. These findings suggest that acute injury to the superficial
      neocortical layers results in a disinhibition of cortical circuits that stems
      from a decline in GABA release likely due to the loss of superficial inhibitory
      interneurons and an enhancement of synaptic excitation consequent to an increase
      in the AMPA receptor unit conductance.

PMID- 16987929
TI  - Laterality of the command center in relation to handedness and simple reaction
      time: a clinical perspective.

PMID- 16987930
TI  - Effects of small ischemic lesions in the primary motor cortex on
      neurophysiological organization in ventral premotor cortex.
AB  - After a cortical lesion, cortical areas distant from the site of injury are known
      to undergo physiological and anatomical changes. However, the mechanisms through
      which reorganization of distant cortical areas is initiated are poorly
      understood. In a previous publication, we showed that the ventral premotor cortex
      (PMv) undergoes physiological reorganization after a lesion destroying the
      majority of the primary motor cortex (M1) distal forelimb representation (DFL).
      After large lesions destroying >50% of the M1 DFL, the PMv DFL invariably
      increased in size, and the amount of the increase was positively correlated with
      the size of lesion. To determine whether lesions destroying <50% of the M1 DFL
      followed a similar trajectory, we documented PMv reorganization using
      intracortical microstimulation techniques after small, ischemic lesions targeting
      subregions within the M1 DFL. In contrast to earlier results, lesions resulted in
      a reduction of the PMv DFL regardless of their location. Further, because recent
      anatomical findings suggest a segregation of PMv connectivity with M1, we
      examined two lesion characteristics that may drive alterations in PMv
      physiological reorganization: location of the lesion with respect to PMv
      connectivity and relative size of the lesion. The results suggest that after a
      lesion in the M1 DFL, the induction of representational plasticity in PMv, as
      evaluated using intracortical microstimulation, is related more to the size of
      the lesion than to the disruption of its intracortical connections.

PMID- 16987931
TI  - Dynamic synchronization of Purkinje cell simple spikes.
AB  - Purkinje cells (PCs) integrate all computations performed in the cerebellar
      cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes
      recorded in vivo from pairs of PCs separated by <100 microm are known to be
      synchronized with a sharp peak riding on a broad peak, but the significance of
      this finding is unclear. We show that the sharp peak consists exclusively of
      simple spikes associated with pauses in firing. The broader, less precise peak
      was caused by firing-rate co-modulation of faster firing spikes. About 13% of all
      pauses were synchronized, and these pauses had a median duration of 20 ms. As in
      vitro studies have reported that synchronous pauses can reliably trigger spikes
      in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is
      important for precise temporal coding in the cerebellum.

PMID- 16987932
TI  - Alpha1-antichymotrypsin, an inflammatory protein overexpressed in Alzheimer's
      disease brain, induces tau phosphorylation in neurons.
AB  - Amyloid plaques and neurofibrillary tangles are key pathological features of
      Alzheimer's disease. Alzheimer's disease pathology is also characterized by
      neuroinflammation and neuronal degeneration, with the proteins associated with
      inflammatory responses being found in tight association with the plaques. One
      such protein is the serine protease inhibitor alpha-1-antichymotrypsin (ACT). ACT
      has been shown to promote Abeta polymerization in vitro and in vivo, and levels
      of ACT protein in plasma and cerebrospinal fluid from Alzheimer's patients have
      been found to correlate with progression of dementia. Here we investigated the
      possible involvement of ACT in tau phosphorylation and tangle formation. As was
      previously found for Alzheimer's disease, brains from patients with non
      Alzheimer's tauopathies exhibited an enhanced expression of ACT, which correlated
      with the level of tau hyperphosphorylation. Transgenic mice expressing human ACT
      alone or ACT along with mutant human amyloid precursor protein (APP) showed a
      significant increase in tau phosphorylation, suggesting that this inflammatory
      protein can induce tau hyperphosphorylation. The increase in phosphorylation was
      observed at PHF-1 (P-Ser396/P-Thr404), P-Ser202 and P-Thr231 sites on tau, the P
      tau epitopes that are associated with tangles in the patients. This result was
      further confirmed by the finding that addition of purified ACT induced the same
      Alzheimer's disease-related tau hyperphosphorylation in cortical neurons cultured
      in vitro. This correlated with an increase in extracellular signal regulated
      kinase (ERK) and glycogen synthase kinase-3 activation, indicating their
      involvement in ACT-induced tau phosphorylation. The ACT-treated neurons showed
      neurite loss and subsequently underwent apoptosis. Approximately 40-50% of
      neurons were TUNEL positive by 6 and at 24 h >70% of the neurons showed staining
      suggesting that ACT was inducing apoptosis in these neurons. These findings
      indicate that inappropriate inflammatory responses are a potential threat to the
      brain and that intervention directed at inhibiting the expression or function of
      ACT could be of therapeutic value in neurodegenerative diseases such as
      Alzheimer's and other tauopathies.

PMID- 16987933
TI  - U.S. health system performance: a national scorecard.
AB  - This paper presents the findings of a new scorecard designed to assess and
      monitor multiple domains of U.S. health system performance. The scorecard uses
      national and international data to identify performance benchmarks and calculates
      simple ratio scores comparing U.S averages to benchmarks. Average ratio scores
      range from 51 to 71 across domains of health outcomes, quality, access, equity,
      and efficiency. The overall picture that emerges from the scorecard is one of
      missed opportunities and room for improvement. The findings underscore the
      importance of policies that take a coherent, whole-system approach to change and
      address the interaction of access, quality, and cost.

PMID- 16987934
TI  - The 8.1 ancestral MHC haplotype is associated with delayed onset of colonization
      in cystic fibrosis.
AB  - Major cause of death in patients with cystic fibrosis (CF) is colonization with
      Staphylococcus aureus and Pseudomonas aeruginosa. The wide phenotypic variation
      in CF patients suggests that genes other than the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene modify the disease. The 8.1 ancestral haplotype
      (8.1AH) in main histocompatibility complex is associated with alterations of the
      immune response. To study the influence of carriage of 8.1AH on frequency and
      onset of colonization in CF patients, DNA samples of 72 CF patients (39
      homozygous and 33 heterozygous for DeltaF508) were genotyped for member alleles
      of the 8.1AH: HLA-DQB1*0201, HLA-DRB1*0301, receptor for advanced glycation end
      products (AGER) -429C, HSP70-2 -1267G (HSP70-2G) and tumor necrosis factor-alpha
      (TNF-alpha) -308A (TNF2). Colonization was verified by regular clinical and
      bacteriological screening. Frequency of colonization was significantly (P =
      0.012) lower in the 8.1AH carriers; age, gender and DeltaF508 genotype-adjusted
      odds ratio to be colonized of the carriers versus non-carriers was 0.112 (0.024
      0.520). According to survival analysis, patients with 8.1AH had significantly (P
      < 0.0001) longer colonization-free period compared with non-carriers. Our novel
      observations demonstrate that the 8.1AH is associated with delayed onset of
      colonization in CF, presumably by influencing defense mechanisms against
      infections.

PMID- 16987935
TI  - Tumor cell expression of HLA-DM associates with a Th1 profile and predicts
      improved survival in breast carcinoma patients.
AB  - Studies aimed at elucidating the immunological and prognostic significance of HLA
      DR expression on breast carcinoma cells have yielded contradictory results. To
      expand on previous studies, we have investigated the associations of tumor cell
      expression of HLA-DR and its related co-chaperones, invariant chain (Ii) and HLA
      DM, with infiltrating inflammatory cells, in situ cytokine mRNA levels and
      prognosis and outcome in 112 breast carcinoma patients with a median follow-up of
      59 months. While the majority of HLA-DR+ tumors co-express Ii, only a minority
      express HLA-DM. Tumor cell expression of HLA-DR and co-chaperones positively
      associated with both infiltrating CD4+ and CD8+ T-cell subsets (P < 0.01).
      Expression of HLA-DR and Ii associated with decreased estrogen receptor alpha
      levels and younger age at diagnosis, suggesting a role for hormones in the
      control of HLA class II expression in breast carcinoma. Patients with DR+Ii+DM-
      tumors had markedly decreased recurrence-free and disease-specific survival as
      compared with patients with DR+Ii+DM+ tumors (P < 0.05) and HLA-DR/co-chaperone
      expression was an independent predictor of survival by multivariate Cox
      regression analysis, controlling for standard prognostic indicators. Tumors that
      co-express HLA-DR, Ii and HLA-DM have increased levels of IFN-gamma, IL-2 and IL
      12 mRNA, suggesting improved survival of patients with DR+Ii+DM+ tumors may be
      attributable to Th1-dominated immunity. We conclude that expression of
      determinants of the immune response by tumor cells may influence breast tumor
      progression and patient outcome.

PMID- 16987936
TI  - Competition controls the rate of transition between the peripheral pools of
      CD4+CD25- and CD4+CD25+ T cells.
AB  - Recent reports have hinted that it is possible to regenerate CD4+CD25+ regulatory
      T cells (Treg) from CD4+CD25- cells, a phenomenon termed conversion. We evaluated
      the relative contribution of this process to the Treg pool by transferring
      purified populations of CD4+ T cells into T cell-deficient mice. We report that
      conversion of CD25- cells into the CD4+CD25+Treg pool is minor if other bona fide
      CD25+ Tregs are present. Moreover, in the same hosts, the loss of CD25 expression
      by a population of Tregs also decreases in the presence of co-injected CD4+CD25-
      cells. Thus, the rate of exchange between CD25- and CD25+ T-cell populations is
      determined by the presence or absence of T-cell competitors. Our results attest
      for the role of competition in the contribution of different T-cell subsets for
      the regeneration of the peripheral CD4+ T-cell pool during lymphopenia.

PMID- 16987937
TI  - Infraspecific DNA methylation polymorphism in cotton (Gossypium hirsutum L.).
AB  - Cytosine methylation is important in the epigenetic regulation of gene expression
      and development in plants and has been implicated in silencing duplicate genes
      after polyploid formation in several plant groups. Relatively little information
      exists, however, on levels and patterns of methylation polymorphism (MP) at
      homologous loci within species. Here we explored the levels and patterns of
      methylation-polymorphism diversity at CCGG sites within allotetraploid cotton,
      Gossypium hirsutum, using a methylation-sensitive amplified fragment length
      polymorphism screen and a selected set of 20 G. hirsutum accessions for which we
      have information on genetic polymorphism levels and relationships. Methylation
      and MP exist at high levels within G. hirsutum: of 150 HpaII/MspI sites surveyed,
      48 were methylated at the inner cytosine (32%) and 32 of these were polymorphic
      (67%). Both these values are higher than comparable measures of genetic diversity
      using restriction fragment length polymorphisms. The high percentage of
      methylation-polymorphic sites and potential relationship to gene expression
      underscore the potential significance of MP within and among populations. We
      speculate that biased correlation of methylation-polymorphic sites and genes in
      cotton may be a consequence of polyploidy and the attendant doubling of all
      genes.

PMID- 16987938
TI  - A comparison of rarefaction and bayesian methods for predicting the allelic
      richness of future samples on the basis of currently available samples.
AB  - Rarefaction methods have been introduced into population genetics (from ecology)
      for predicting and comparing the allelic richness of future samples (or sometimes
      populations) on the basis of currently available samples, possibly of different
      sizes. Here, we focus our attention on one such problem: Predicting which
      population is most likely to yield the future sample having the highest allelic
      richness. (This problem can arise when we want to construct a core collection
      from a larger germplasm collection.) We use extensive simulations to compare the
      performance of the Monte Carlo rarefaction (repeated random subsampling) method
      with a simple Bayesian approach we have developed-which is based on the Ewens
      sampling distribution. We found that neither this Bayesian method nor the (Monte
      Carlo) rarefaction method performed uniformly better than the other. We also
      examine briefly some of the other motivations offered for these methods and try
      to make sense of them from a Bayesian point of view.

PMID- 16987939
TI  - Engineering of cytochrome P450 3A4 for enhanced peroxide-mediated substrate
      oxidation using directed evolution and site-directed mutagenesis.
AB  - CYP3A4 has been subjected to random and site-directed mutagenesis to enhance
      peroxide-supported metabolism of several substrates. Initially, a high-throughput
      screening method using whole cell suspensions was developed for H2O2-supported
      oxidation of 7-benzyloxyquinoline. Random mutagenesis by error-prone polymerase
      chain reaction and activity screening yielded several CYP3A4 mutants with
      enhanced activity. L216W and F228I showed a 3-fold decrease in Km, HOOH and a 2.5
      fold increase in kcat/Km, HOOH compared with CYP3A4. Subsequently, T309V and
      T309A were created based on the observation that T309V in CYP2D6 has enhanced
      cumene hydroperoxide (CuOOH)-supported activity. T309V and T309A showed a > 6-
      and 5-fold higher kcat/Km, CuOOH than CYP3A4, respectively. Interestingly, L216W
      and F228I also exhibited, respectively, a > 4- and a > 3-fold higher kcat/Km,
      CuOOH than CYP3A4. Therefore, several multiple mutants were constructed from
      rationally designed and randomly isolated mutants; among them, F228I/T309A showed
      an 11-fold higher kcat/Km, CuOOH than CYP3A4. Addition of cytochrome b5, which is
      known to stimulate peroxide-supported activity, enhanced the kcat/Km, CuOOH of
      CYP3A4 by 4- to 7-fold. When the mutants were tested with other substrates, T309V
      and T433S showed enhanced kcat/Km, CuOOH with 7-benzyloxy-4
      (trifluoromethyl)coumarin and testosterone, respectively, compared with CYP3A4.
      In addition, in the presence of cytochrome b5, T433S has the potential to produce
      milligram quantities of 6beta-hydroxytestosterone through peroxide-supported
      oxidation. In conclusion, a combination of random and site-directed mutagenesis
      approaches yielded CYP3A4 enzymes with enhanced peroxide-supported metabolism of
      several substrates.

PMID- 16987940
TI  - Social construction and cultural meanings of STI/HIV-related terminology among
      Nguni-speaking inmates and warders in four South African correctional facilities.
AB  - Cultural sensitivity is increasingly recognized as a means to enhance the
      effectiveness of health promotion programmes all over the world. Sociocultural
      meanings and terminology of diseases are important in understanding how different
      groups perceive and interpret illness. This study was conducted as part of the
      process of developing and adapting a sexually transmitted infection (STI)/HIV
      peer led health education intervention for soon-to-be-released inmates who were
      predominantly Nguni speakers in South Africa. Two focus group discussions (FGDs)
      were conducted with prison inmates in each of four facilities. Additionally, one
      FGD was conducted in each prison with non-health trained (custodial) personnel
      who were Nguni speakers from the same community (n = 27). The data revealed
      unique terminology and meanings attached to several biomedically defined STIs.
      These sociocultural constructions were not limited to inmates as findings from
      warders' discussions showed a similar pattern. Moreover, we found the existence
      of a number of traditional 'folk' STIs and culture-specific prevention methods.
      These conceptualizations influence reported health-care-seeking behaviour, where
      dual consultation of traditional healers and biomedical remedies is widely
      practiced. The research has biopsychological as well as cultural implications for
      the development and adaptation of contextually relevant health promotion
      interventions.

PMID- 16987941
TI  - The impact of school smoking policies and student perceptions of enforcement on
      school smoking prevalence and location of smoking.
AB  - The purpose of this study was to comprehensively assess the impact of school
      tobacco policy intention, implementation and students' perceptions of policy
      enforcement on smoking rates and location of tobacco use during the school day.
      Data were obtained from all students in Grades 10-11 (n = 22,318) in 81 randomly
      selected schools from five Canadian provinces. Policy intention was assessed by
      coding written school tobacco policies. School administrators most familiar with
      the tobacco policy completed a survey to assess policy implementation. Results
      revealed policy intention and implementation subscales did not significantly
      predict school smoking prevalence but resulted in moderate prediction of tobacco
      use on school property (R(2) = 0.21-0.27). Students' perceptions of policy
      enforcement significantly predicted school smoking prevalence (R(2) = 0.36) and
      location of tobacco use (R(2) = 0.23-0.63). The research findings emphasize: (i)
      the need to consider both written policy intention and actual policy
      implementation and (ii) the existence of a policy is not effective in controlling
      tobacco use unless the policy is implemented and is perceived to be strongly
      enforced.

PMID- 16987942
TI  - Social desirability is associated with some physical activity, psychosocial
      variables and sedentary behavior but not self-reported physical activity among
      adolescent males.
AB  - This study examined whether controlling for social desirability improved the
      association between self-reported and objectively measured physical activity
      among adolescent males and the extent that psychosocial variables predict
      physical activity after controlling for social desirability. Participants (n=447)
      were 10- to 14-year old Houston Boy Scouts. Participants completed self-reports
      of physical activity, sedentary behavior, preferences, self-efficacy and social
      desirability and wore an MTI accelerometer for 3 days. Correlations were
      conducted among variables. Regression models were performed to examine the
      relationships between objectively measured (accelerometer) and self-reported
      physical activity, objectively measured physical activity and psychosocial
      variables and self-reports of physical activity and psychosocial variables. All
      models controlled for social desirability. There were weak associations between
      self-reported and objectively measured physical activity measures that were
      slightly improved after controlling for social desirability. Psychosocial
      variables were strongly associated with self-reports of physical activity, but
      weakly associated with accelerometer physical activity. Social desirability was
      positively associated with physical activity preferences (r=0.169) and self
      efficacy (r=0.118) and negatively associated (r=-0.158) with self-reported
      sedentary behavior. Differences in the strength of relationships between self
      reported and objectively measured physical activity and psychosocial variables
      were not a function of social desirability.

PMID- 16987943
TI  - 'If I don't smoke, I'm not a real man'--Indonesian teenage boys' views about
      smoking.
AB  - With a lack of tobacco control and regulation at the national level, Indonesia
      has been targeted by many national and transnational tobacco companies. The
      prevalence of youth smokers in Indonesia in 2005 was 38% among boys and 5.3%
      among girls. The aim of this study was to describe and analyse beliefs, norms and
      values about smoking among teenage boys in a rural setting in Java, Indonesia.
      Six focus group discussions with boys aged 13-17 years were conducted using a
      thematic discussion guide. Four themes were derived from the descriptive content
      analysis: (i) smoking as a culturally internalized habit, (ii) striving to become
      a man, (iii) the way we smoke is not dangerous and (iv) the struggle against
      dependency. Cultural resistance against women smoking in Indonesia remains
      strong. The use of tobacco in the construction of masculinity underlines the
      importance of gender-specific intervention. National tobacco control policy
      should emphasize a smoking-free society as the norm, especially among boys and
      men, and regulations regarding the banning of smoking should be enforced at all
      levels and areas of community. A comprehensive community intervention programme
      on smoking prevention and cessation should be a major focus of tobacco control
      policies in Indonesia.

PMID- 16987944
TI  - Effect of amino acid replacements on the structural stability of fish myoglobin.
AB  - Structural stabilities of myoglobin (Mb) from several fish (scombridae) species
      differ significantly, although their amino acid sequence identity is very high
      (>95%), suggesting that only a few substitutions greatly affect the stability of
      Mb. Accordingly, recombinant Mbs with point mutation(s) derived from bigeye tuna
      Mb cDNA were expressed as GST-fusion proteins in the soluble fractions of
      Escherichia coli. After removal of the GST segment, the stability of five
      mutants, namely, P13A, I21M, V57I, A62G, and I21M/V57I, together with the wild
      type (WT) were investigated, taking temperature dependency of alpha-helical
      content and denaturant concentration dependency of Soret band absorbance as
      parameters. As a result, the stability of P13A against denaturants and its alpha
      helical content at 10 degrees C was found to be the highest among the mutants,
      whereas those of A62G were the lowest. The stabilities of V57I and I21M/V57I were
      higher than that of WT, though that of I21M was nearly the same as WT. These
      findings suggest that the structural stability of fish Mb is tuned up only by the
      substitutions of a few amino acid residues located in the alpha-helical segments
      forming the hydrophobic heme pocket.

PMID- 16987945
TI  - New evidence for ATP binding induced catalytic subunit interactions in pig kidney
      Na/K-ATPase.
AB  - Pig kidney Na/K-ATPase preparations showed a positive cooperative effect for pNPP
      in Na-pNPPase activity. Measurements of the Na-pNPPase activity, Na-ATPase
      activity and the accumulation of phosphoenzyme (EP) under conditions of pNPP
      saturation showed several different ATP affinities. The presence of pNPP reduced
      both the maximum amount of EP and Na-ATPase activity to half showing a value of 4
      and a 3,700-fold reduced ATP affinity for EP formation, and a 7 and 1,300-fold
      reduced affinity for Na-ATPase activity. The presence of low concentrations of
      ATP in the phosphorylation induced a 2-fold enhancement in Na-pNPPase activity
      despite a reduction in available pNPP sites. However, higher concentrations of
      ATP inhibited the Na-pNPPase activity and a much higher concentration of ATP
      increased both the phosphorylation and Na-ATPase activity to the maximum levels.
      The maximum Na-pNPPase activity was 1.7 and 3.4-fold higher without and with ATP,
      respectively, than the maximum Na-ATPase activity. These data and the pNPP
      dependent reduction in both Na-ATPase activity and the amount of enzyme bound ATP
      provide new evidence to show that ATP, pNPP and ATP with pNPP, respectively,
      induce different subunit interactions resulting a difference in the maximum Na(+)
      dependent catalytic activity in tetraprotomeric Na/K-ATPase.

PMID- 16987946
TI  - American College of Cardiology/American Heart Association 2006 update of the
      clinical competence statement on invasive electrophysiology studies, catheter
      ablation, and cardioversion: a report of the American College of
      Cardiology/American Heart Association/American College of Physicians Task Force
      on Clinical Competence and Training: developed in collaboration with the Heart
      Rhythm Society.

PMID- 16987947
TI  - Course of depressive symptoms after myocardial infarction and cardiac prognosis:
      a latent class analysis.
AB  - OBJECTIVE: The presence of depressive symptoms after myocardial infarction (MI)
      is a risk factor for new cardiovascular events. The importance of the course of
      post-MI depressive symptoms for cardiac prognosis is not clear. We therefore set
      out to investigate whether different courses of post-MI depressive symptoms can
      be identified and determine their associations with cardiac events. METHODS: Data
      were derived from the Depression after Myocardial Infarction (DepreMI) study, a
      naturalistic follow-up study of patients admitted for an MI in four hospitals in
      The Netherlands (N = 475). Scores on the Beck Depression Inventory (BDI) during
      hospitalization and at 3, 6, and 12 months post-MI were analyzed. Using latent
      class analysis (LCA), we identified classes characterized by distinctive courses
      of depressive symptoms and then examined their link to cardiac prognosis.
      RESULTS: The prevalence of significant depressive symptoms ranged from 22.7% to
      25.5% throughout the post-MI year. Five distinct courses were found: no
      depressive symptoms (56.4%), mild depressive symptoms (25.7%), moderate and
      increasing depressive symptoms (9.3%), significant but decreasing depressive
      symptoms (4.6%), and significant and increasing depressive symptoms (4.0%).
      Subjects in this last class had, statistically, a significantly higher risk for a
      new cardiovascular event compared with subjects without depressive symptoms
      (hazard ratio (HR) = 2.73; p = .01). Controlling for baseline cardiac status and
      sociodemographic data did not alter the association (HR = 2.46; p = .03).
      CONCLUSIONS: Post-MI depressed subjects with significant and increasing
      depressive symptoms are at particular risk of new cardiac events. This subgroup
      may be most suited for evaluation of the effects of antidepressant treatment on
      cardiac prognosis.

PMID- 16987948
TI  - Work hours affect spouse's cortisol secretion--for better and for worse.
AB  - OBJECTIVE: In a sample of 52 German dual-earner couples with at least one child
      under age 5, we examined the bodily costs and benefits of the amount of time each
      spouse spent on productive activities. METHODS: Diary reports of time allocated
      to formal and informal work activities were analyzed according to the Actor
      Partner Interdependence model. RESULTS: Hierarchical linear models showed that
      each hour an individual allocated to market, as well as household work, increased
      his or her total cortisol concentration (by 192 and 134 nmol/l, respectively).
      Unexpectedly, the time the spouse allocated to paid work also raised an
      individual's total cortisol concentration (by 64 nmol/l). In line with our
      expectations, there was a tendency for the time the spouse allocated to household
      work to decrease the individual's cortisol concentration (by 81 nmol/l).
      CONCLUSIONS: This study contributes to the body of evidence on the complex nature
      of social relationships and complements the literature on specific working
      conditions and couples' well-being.

PMID- 16987949
TI  - A large patient study confirming that facioscapulohumeral muscular dystrophy
      (FSHD) disease expression is almost exclusively associated with an FSHD locus
      located on a 4qA-defined 4qter subtelomere.
AB  - Facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant disorder,
      represents the third most common human muscular dystrophy. The FSHD disease
      locus, at chromosome 4q35, is associated with large contractions of the
      polymorphic repeat sequence array D4Z4. In addition to FSHD disease association
      with large D4Z4 deletions, a biased interaction with a specific 4qter
      subtelomeric sequence has been described in patients. Two distinct 4qter
      subtelomeres, defined as types 4qA and 4qB, have been identified and shown to be
      equally prevalent in the Caucasian population. In almost all 4q35-linked patients
      with FSHD, however, disease expression only occurs when large D4Z4 deletions are
      located on 4qA-defined 4qter subtelomeres. Conversely, large D4Z4 repeat
      contractions situated on 4qB-defined subtelomeres either are not disease-causing
      or exhibit a greatly reduced disease penetrance. This study was initiated to
      confirm this direct FSHD disease association data by measuring the frequency of
      type 4qA-defined and 4qB-defined subtelomeric sequences in a large cohort of 164
      unrelated patients with FSHD from Turkey and the UK, all known to have large D4Z4
      deletions. An almost complete association was found between large D4Z4 repeat
      array deletions located on 4qA-defined 4qter subtelomeres and disease expression
      in our large FSHD patient cohort. The observed failure of probes 4qA and 4qB to
      hybridise to two patient-derived DNA samples confirms the presence of an
      additional rare type of 4qter subtelomeric sequence in humans.

PMID- 16987950
TI  - The shoot stem cell niche in angiosperms: expression patterns of WUS orthologues
      in rice and maize imply major modifications in the course of mono- and dicot
      evolution.
AB  - In Arabidopsis, stem cell homeostasis in the shoot apical meristem (SAM) is
      controlled by a feedback loop between WUS and CLV functions. We have identified
      WUS orthologues in maize and rice by a detailed phylogenetic analysis of the WOX
      gene family and subsequent cloning. A single WUS orthologue is present in the
      rice genome (OsWUS), whereas the allotetraploid maize genome contains 2 WUS
      paralogues (ZmWUS1 and ZmWUS2). None of the isolated grass WUS orthologues
      displays an organizing center-type expression pattern in the vegetative SAM as in
      Arabidopsis. In contrast, the grass-specific expression patterns relate to the
      specification of new phytomers consistent with the transcriptional expression
      patterns of TD1 and FON1 (CLV1 orthologues of maize and rice, respectively).
      Moreover, the grass WUS and CLV1 orthologues are coexpressed in all reproductive
      meristems, where fasciation and supernumerary floral organs occur in td1 or fon1
      loss-of-function mutants. The expression patterns of WUS orthologues in both
      grass species compared with those of dicots imply that major changes in WUS
      function, which are correlated with changes in CLV1 signaling, have occurred
      during angiosperm evolution and raise doubts about the uniqueness of the WUS/CLV
      antagonism in the maintenance of the shoot stem cell niche in grasses.

PMID- 16987951
TI  - Supernetwork identifies multiple events of plastid trnF(GAA) pseudogene evolution
      in the Brassicaceae.
AB  - The occurrence of nonfunctional trnF pseudogenes has been rarely described in
      flowering plants. However, we describe the first large-scale supernetwork for the
      Brassiccaeae built from gene trees for 5 loci (adh, chs, matK, trnL-F, and ITS)
      and report multiple independent origins for trnF pseudogenes in crucifers. The
      duplicated regions of the original trnF gene are comprised of its anticodon
      domain and several other highly structured motifs not related to the original
      gene. Length variation of the trnL-F intergenic spacer region in different taxa
      ranges from 219 to 900 bp as a result of differences in pseudocopy number (1-14).
      It is speculated that functional constraints favor 2-3 or 5-6 copies, as found in
      Arabidopsis and Boechera. The phylogenetic distribution of microstructural
      changes for the trnL-F region supports ancient patterns of divergence in crucifer
      evolution for some but not all gene loci.

PMID- 16987952
TI  - Transcription and evolutionary dynamics of the centromeric satellite repeat CentO
      in rice.
AB  - Satellite DNA is a major component of centromeric heterochromatin in most
      multicellular eukaryotes, where it is typically organized into megabase-sized
      tandem arrays. It has recently been demonstrated that small interfering RNAs
      (siRNAs) processed from centromeric satellite repeats can be involved in
      epigenetic chromatin modifications which appear to underpin centromere function.
      However, the structural organization and evolution of the centromeric satellite
      DNA is still poorly understood. We analyzed the centromeric satellite repeat
      arrays from rice chromosomes 1 and 8 and identified higher order structures and
      local homogenization of the CentO repeats in these 2 centromeres. We also cloned
      the CentO repeats from the CENH3-associated nucleosomes by a chromatin
      immunoprecipitation (ChIP)-based method. Sequence variability analysis of the
      ChIPed CentO repeats revealed a single variable domain within the repeat. We
      detected transcripts derived from both strands of the CentO repeats. The CentO
      transcripts are processed into siRNA, suggesting a potential role of this
      satellite repeat family in epigenetic chromatin modification.

PMID- 16987953
TI  - Large global effective population sizes in Paramecium.
AB  - The genetic effective population size (N(e)) of a species is an important
      parameter for understanding evolutionary dynamics because it mediates the
      relative effects of selection. However, because most N(e) estimates for
      unicellular organisms are derived either from taxa with poorly understood species
      boundaries or from host-restricted pathogens and most unicellular species have
      prominent phases of clonal propagation potentially subject to strong selective
      sweeps, the hypothesis that N(e) is elevated in single-celled organisms remains
      controversial. Drawing from observations on well-defined species within the genus
      Paramecium, we report exceptionally high levels of silent-site polymorphism,
      which appear to be a reflection of large N(e).

PMID- 16987954
TI  - Tracking of quantum dot-labeled CFTR shows near immobilization by C-terminal PDZ
      interactions.
AB  - Mutations in cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP
      regulated chloride channel, cause cystic fibrosis. To investigate interactions of
      CFTR in living cells, we measured the diffusion of quantum dot-labeled CFTR
      molecules by single particle tracking. In multiple cell lines, including airway
      epithelia, CFTR diffused little in the plasma membrane, generally not moving
      beyond 100-200 nm. However, CFTR became mobile over micrometer distances after 1)
      truncations of the carboxy terminus, which contains a C-terminal PDZ
      (PSD95/Dlg/ZO-1) binding motif; 2) blocking PDZ binding by C-terminal green
      fluorescent protein fusion; 3) disrupting CFTR association with actin by
      expression of a mutant EBP50/NHERF1 lacking its ezrin binding domain; or 4)
      skeletal disruption by latrunculin. CFTR also became mobile when the cytoskeletal
      adaptor protein binding capacity was saturated by overexpressing CFTR or its C
      terminus. Our data demonstrate remarkable and previously unrecognized
      immobilization of CFTR in the plasma membrane and provide direct evidence that C
      terminal coupling to the actin skeleton via EBP50/ezrin is responsible for its
      immobility.

PMID- 16987955
TI  - Systematic deletion and mitotic localization of the nuclear pore complex proteins
      of Aspergillus nidulans.
AB  - To define the extent of the modification of the nuclear pore complex (NPC) during
      Aspergillus nidulans closed mitosis, a systematic analysis of nuclear transport
      genes has been completed. Thirty genes have been deleted defining 12 nonessential
      and 18 essential genes. Several of the nonessential deletions caused conditional
      phenotypes and self-sterility, whereas deletion of some essential genes caused
      defects in nuclear structure. Live cell imaging of endogenously tagged NPC
      proteins (Nups) revealed that during mitosis 14 predicted peripheral Nups,
      including all FG repeat Nups, disperse throughout the cell. A core mitotic NPC
      structure consisting of membrane Nups, all components of the An-Nup84 subcomplex,
      An-Nup170, and surprisingly, An-Gle1 remained throughout mitosis. We propose this
      minimal mitotic NPC core provides a conduit across the nuclear envelope and acts
      as a scaffold to which dispersed Nups return during mitotic exit. Further, unlike
      other dispersed Nups, An-Nup2 locates exclusively to mitotic chromatin,
      suggesting it may have a novel mitotic role in addition to its nuclear transport
      functions. Importantly, its deletion causes lethality and defects in DNA
      segregation. This work defines the dramatic changes in NPC composition during A.
      nidulans mitosis and provides insight into how NPC disassembly may be integrated
      with mitosis.

PMID- 16987957
TI  - A Phg2-Adrm1 pathway participates in the nutrient-controlled developmental
      response in Dictyostelium.
AB  - Dictyostelium amoebae grow as single cells but upon starvation they initiate
      multicellular development. Phg2 was characterized previously as a kinase
      controlling cellular adhesion and the organization of the actin cytoskeleton.
      Here we report that Phg2 also plays a role during the transition between growth
      and multicellular development, as evidenced by the fact that phg2 mutant cells
      can initiate development even in the presence of nutrients. Even at low cell
      density and in rich medium, phg2 mutant cells express discoidin, one of the
      earliest predevelopmental markers. Complementation studies indicate that, in
      addition to the kinase domain, the core region of Phg2 is involved in the
      initiation of development. In this region, a small domain contiguous with a
      previously described ras-binding domain was found to interact with the
      Dictyostelium ortholog of the mammalian adhesion-regulating molecule (ADRM1). In
      addition, adrm1 knockout cells also exhibit abnormal initiation of development.
      These results suggest that a Phg2-Adrm1 signaling pathway is involved in the
      control of the transition from growth to differentiation in Dictyostelium. Phg2
      thus plays a dual role in the control of cellular adhesion and initiation of
      development.

PMID- 16987956
TI  - C2B polylysine motif of synaptotagmin facilitates a Ca2+-independent stage of
      synaptic vesicle priming in vivo.
AB  - Synaptotagmin I, a synaptic vesicle protein required for efficient synaptic
      transmission, contains a highly conserved polylysine motif necessary for
      function. Using Drosophila, we examined in which step of the synaptic vesicle
      cycle this motif functions. Polylysine motif mutants exhibited an apparent
      decreased Ca2+ affinity of release, and, at low Ca2+, an increased failure rate,
      increased facilitation, and increased augmentation, indicative of a decreased
      release probability. Disruption of Ca2+ binding, however, cannot account for all
      of the deficits in the mutants; rather, the decreased release probability is
      probably due to a disruption in the coupling of synaptotagmin to the release
      machinery. Mutants exhibited a major slowing of recovery from synaptic
      depression, which suggests that membrane trafficking before fusion is disrupted.
      The disrupted process is not endocytosis because the rate of FM 1-43 uptake was
      unchanged in the mutants, and the polylysine motif mutant synaptotagmin was able
      to rescue the synaptic vesicle depletion normally found in syt(null) mutants.
      Thus, the polylysine motif functions after endocytosis and before fusion.
      Finally, mutation of the polylysine motif inhibits the Ca2+-independent ability
      of synaptotagmin to accelerate SNARE (soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor)-mediated fusion. Together, our results demonstrate
      that the polylysine motif is required for efficient Ca2+-independent docking
      and/or priming of synaptic vesicles in vivo.

PMID- 16987958
TI  - Enhancement of U4/U6 small nuclear ribonucleoprotein particle association in
      Cajal bodies predicted by mathematical modeling.
AB  - Spliceosomal small nuclear ribonucleoprotein particles (snRNPs) undergo specific
      assembly steps in Cajal bodies (CBs), nonmembrane-bound compartments within cell
      nuclei. An example is the U4/U6 di-snRNP, assembled from U4 and U6 monomers.
      These snRNPs can also assemble in the nucleoplasm when cells lack CBs. Here, we
      address the hypothesis that snRNP concentration in CBs facilitates assembly, by
      comparing the predicted rates of U4 and U6 snRNP association in nuclei with and
      without CBs. This was accomplished by a random walk-and-capture simulation
      applied to a three-dimensional model of the HeLa cell nucleus, derived from
      measurements of living cells. Results of the simulations indicated that snRNP
      capture is optimal when nuclei contain three to four CBs. Interestingly, this is
      the observed number of CBs in most cells. Microinjection experiments showed that
      U4 snRNA targeting to CBs was U6 snRNP independent and that snRNA concentration
      in CBs is approximately 20-fold higher than in nucleoplasm. Finally, combination
      of the simulation with calculated association rates predicted that the presence
      of CBs enhances U4 and U6 snRNP association by up to 11-fold, largely owing to
      this concentration difference. This provides a chemical foundation for the
      proposal that these and other cellular compartments promote molecular
      interactions, by increasing the local concentration of individual components.

PMID- 16987959
TI  - Global organization and function of mammalian cytosolic proteasome pools:
      Implications for PA28 and 19S regulatory complexes.
AB  - Proteolytic activity of the 20S proteasome is regulated by activators that govern
      substrate movement into and out of the catalytic chamber. However, the
      physiological relationship between activators, and hence the relative role of
      different proteasome species, remains poorly understood. To address this problem,
      we characterized the total pool of cytosolic proteasomes in intact and functional
      form using a single-step method that bypasses the need for antibodies, proteasome
      modification, or column purification. Two-dimensional Blue Native(BN)/SDS-PAGE
      and tandem mass spectrometry simultaneously identified six native proteasome
      populations in untreated cytosol: 20S, singly and doubly PA28-capped, singly 19S
      capped, hybrid, and doubly 19S-capped proteasomes. All proteasome species were
      highly dynamic as evidenced by recruitment and exchange of regulatory caps. In
      particular, proteasome inhibition with MG132 markedly stimulated PA28 binding to
      exposed 20S alpha-subunits and generated doubly PA28-capped and hybrid
      proteasomes. PA28 recruitment virtually eliminated free 20S particles and was
      blocked by ATP depletion. Moreover, inhibited proteasomes remained stably
      associated with distinct cohorts of partially degraded fragments derived from
      cytosolic and ER substrates. These data establish a versatile platform for
      analyzing substrate-specific proteasome function and indicate that PA28 and 19S
      activators cooperatively regulate global protein turnover while functioning at
      different stages of the degradation cycle.

PMID- 16987960
TI  - Myristoylated, alanine-rich C-kinase substrate phosphorylation regulates growth
      cone adhesion and pathfinding.
AB  - Repellents evoke growth cone turning by eliciting asymmetric, localized loss of
      actin cytoskeleton together with changes in substratum attachment. We have
      demonstrated that semaphorin-3A (Sema3A)-induced growth cone detachment and
      collapse require eicosanoid-mediated activation of protein kinase C epsilon (PKC
      epsilon) and that the major PKC epsilon target is the myristoylated, alanine-rich
      C-kinase substrate (MARCKS). Here, we show that PKC activation is necessary for
      growth cone turning and that MARCKS, while at the membrane, colocalizes with
      alpha3-integrin in a peripheral adhesive zone of the growth cone. Phosphorylation
      of MARCKS causes its translocation from the membrane to the cytosol. Silencing
      MARCKS expression dramatically reduces growth cone spread, whereas overexpression
      of wild-type MARCKS inhibits growth cone collapse triggered by PKC activation.
      Expression of phosphorylation-deficient, mutant MARCKS greatly expands growth
      cone adhesion, and this is characterized by extensive colocalization of MARCKS
      and alpha3-integrin, resistance to eicosanoid-triggered detachment and collapse,
      and reversal of Sema3A-induced repulsion into attraction. We conclude that MARCKS
      is involved in regulating growth cone adhesion as follows: its nonphosphorylated
      form stabilizes integrin-mediated adhesions, and its phosphorylation-triggered
      release from adhesions causes localized growth cone detachment critical for
      turning and collapse.

PMID- 16987962
TI  - The formin mDia regulates GSK3beta through novel PKCs to promote microtubule
      stabilization but not MTOC reorientation in migrating fibroblasts.
AB  - In migrating cells, external signals polarize the microtubule (MT) cytoskeleton
      by stimulating the formation of oriented, stabilized MTs and inducing the
      reorientation of the MT organizing center (MTOC). Glycogen synthase kinase 3beta
      (GSK3beta) has been implicated in each of these processes, although whether it
      regulates both processes in a single system and how its activity is regulated are
      unclear. We examined these issues in wound-edge, serum-starved NIH 3T3
      fibroblasts where MT stabilization and MTOC reorientation are triggered by
      lysophosphatidic acid (LPA), but are regulated independently by distinct Rho
      GTPase-signaling pathways. In the absence of other treatments, the GSK3beta
      inhibitors, LiCl or SB216763, induced the formation of stable MTs, but not MTOC
      reorientation, in starved fibroblasts. Overexpression of GSK3beta in starved
      fibroblasts inhibited LPA-induced stable MTs without inhibiting MTOC
      reorientation. Analysis of factors involved in stable MT formation (Rho, mDia,
      and EB1) showed that GSK3beta functioned upstream of EB1, but downstream of Rho
      mDia. mDia was both necessary and sufficient for inducing stable MTs and for up
      regulating GSK3beta phosphorylation on Ser9, an inhibitory site. mDia appears to
      regulate GSK3beta through novel class PKCs because PKC inhibitors and dominant
      negative constructs of novel PKC isoforms prevented phosphorylation of GSK3beta
      Ser9 and stable MT formation. Novel PKCs also interacted with mDia in vivo and in
      vitro. These results identify a new activity for the formin mDia in regulating
      GSK3beta through novel PKCs and implicate novel PKCs as new factors in the MT
      stabilization pathway.

PMID- 16987961
TI  - Phosphoprotein enriched in astrocytes-15 kDa expression inhibits astrocyte
      migration by a protein kinase C delta-dependent mechanism.
AB  - Phosphoprotein enriched in astrocytes-15 kDa (PEA-15), a phosphoprotein enriched
      in astrocytes, inhibits both apoptosis and proliferation in normal and cancerous
      cells. Here, analysis of PEA-15 expression in glioblastoma organotypic cultures
      revealed low levels of PEA-15 in tumor cells migrating away from the explants,
      regardless of the expression levels in the originating explants. Because
      glioblastomas are highly invasive primary brain tumors that can originate from
      astrocytes, we explored the involvement of PEA-15 in the control of astrocyte
      migration. PEA-15-/- astrocytes presented an enhanced motility in vitro compared
      with their wild-type counterparts. Accordingly, NIH-3T3 cells transfected by
      green fluorescent protein-PEA-15 displayed a reduced migration. Reexpression of
      PEA-15 restored PEA-15-/- astrocyte motility to wild-type levels. Pharmacological
      manipulations excluded a participation of extracellular signal-regulated
      kinase/mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt, and
      calcium/calmodulin-dependent protein kinase II in this effect of PEA-15. In
      contrast, treatment by bisindolylmaleimide, Go6976, and rottlerin, and chronic
      application of phorbol 12-myristate 13-acetate and/or bryostatin-1 indicated that
      PKC delta mediated PEA-15 inhibition of astrocyte migration. PEA-15-/- astrocytes
      constitutively expressed a 40-kDa form of PKC delta that was down-regulated upon
      PEA-15 reexpression. Together, these data reveal a new function for PEA-15 in the
      inhibitory control of astrocyte motility through a PKC delta-dependent pathway
      involving the constitutive expression of a catalytic fragment of PKC delta.

PMID- 16987963
TI  - Intranuclear binding kinetics and mobility of single native U1 snRNP particles in
      living cells.
AB  - Uridine-rich small nuclear ribonucleoproteins (U snRNPs) are splicing factors,
      which are diffusely distributed in the nucleoplasm and also concentrated in
      nuclear speckles. Fluorescently labeled, native U1 snRNPs were microinjected into
      the cytoplasm of living HeLa cells. After nuclear import single U1 snRNPs could
      be visualized and tracked at a spatial precision of 30 nm at a frame rate of 200
      Hz employing a custom-built microscope with single-molecule sensitivity. The
      single-particle tracks revealed that most U1 snRNPs were bound to specific
      intranuclear sites, many of those presumably representing pre-mRNA splicing
      sites. The dissociation kinetics from these sites showed a multiexponential decay
      behavior on time scales ranging from milliseconds to seconds, reflecting the
      involvement of U1 snRNPs in numerous distinct interactions. The average dwell
      times for U1 snRNPs bound at sites within the nucleoplasm did not differ
      significantly from those in speckles, indicating that similar processes occur in
      both compartments. Mobile U1 snRNPs moved with diffusion constants in the range
      from 0.5 to 8 microm2/s. These values were consistent with uncomplexed U1 snRNPs
      diffusing at a viscosity of 5 cPoise and U1 snRNPs moving in a largely restricted
      manner, and U1 snRNPs contained in large supramolecular assemblies such as
      spliceosomes or supraspliceosomes.

PMID- 16987964
TI  - The structure of Escherichia coli signal recognition particle revealed by
      scanning transmission electron microscopy.
AB  - Structural studies on various domains of the ribonucleoprotein signal recognition
      particle (SRP) have not converged on a single complete structure of bacterial SRP
      consistent with the biochemistry of the particle. We obtained a three-dimensional
      structure for Escherichia coli SRP by cryoscanning transmission electron
      microscopy and mapped the internal RNA by electron spectroscopic imaging.
      Crystallographic data were fit into the SRP reconstruction, and although the
      resulting model differed from previous models, they could be rationalized by
      movement through an interdomain linker of Ffh, the protein component of SRP.
      Fluorescence resonance energy transfer experiments determined interdomain
      distances that were consistent with our model of SRP. Docking our model onto the
      bacterial ribosome suggests a mechanism for signal recognition involving
      interdomain movement of Ffh into and out of the nascent chain exit site and
      suggests how SRP could interact and/or compete with the ribosome-bound chaperone,
      trigger factor, for a nascent chain during translation.

PMID- 16987965
TI  - A protein encoded by the bovine herpesvirus 1 latency-related gene interacts with
      specific cellular regulatory proteins, including CCAAT enhancer binding protein
      alpha.
AB  - Following acute infection, bovine herpesvirus 1 establishes latency in sensory
      neurons of trigeminal ganglia (TG). Reactivation from latency occurs
      periodically, resulting in the shedding of infectious virus. The latency-related
      (LR) RNA is abundantly expressed in TG of latently infected calves, and the
      expression of LR proteins is necessary for dexamethasone-induced reactivation
      from latency. Previously published studies also identified an alternatively
      spliced LR transcript which is abundantly expressed in TG at 7 days after
      infection and has the potential to encode a novel LR fusion protein. Seven days
      after infection is when extensive viral gene expression is extinguished in TG and
      latency is established, suggesting that LR gene products influence the
      establishment of latency. In this study, we used a bacterial two-hybrid assay to
      identify cellular proteins that interact with the novel LR fusion protein. The LR
      fusion protein interacts with two proteins that can induce apoptosis (Bid and
      Cdc42) and with CCAAT enhancer binding protein alpha (C/EBP-alpha). Additional
      studies confirmed that the LR fusion protein interacts with human or insect C/EBP
      alpha. C/EBP-alpha protein expression is induced in TG neurons of infected calves
      and after dexamethasone-induced reactivation from latency. Wild-type C/EBP-alpha,
      but not a DNA binding mutant of C/EBP-alpha, enhances plaque formation in bovine
      cells. We hypothesize that interactions between the LR fusion protein and C/EBP
      alpha promote the establishment of latency.

PMID- 16987966
TI  - Characterization of White bream virus reveals a novel genetic cluster of
      nidoviruses.
AB  - The order Nidovirales comprises viruses from the families Coronaviridae (genera
      Coronavirus and Torovirus), Roniviridae (genus Okavirus), and Arteriviridae
      (genus Arterivirus). In this study, we characterized White bream virus (WBV), a
      bacilliform plus-strand RNA virus isolated from fish. Analysis of the nucleotide
      sequence, organization, and expression of the 26.6-kb genome provided conclusive
      evidence for a phylogenetic relationship between WBV and nidoviruses. The
      polycistronic genome of WBV contains five open reading frames (ORFs), called
      ORF1a, -1b, -2, -3, and -4. In WBV-infected cells, three subgenomic RNAs
      expressing the structural proteins S, M, and N were identified. The subgenomic
      RNAs were revealed to share a 42-nucleotide, 5' leader sequence that is identical
      to the 5'-terminal genome sequence. The data suggest that a conserved
      nonanucleotide sequence, CA(G/A)CACUAC, located downstream of the leader and
      upstream of the structural protein genes acts as the core transcription
      regulating sequence element in WBV. Like other nidoviruses with large genomes
      (>26 kb), WBV encodes in its ORF1b an extensive set of enzymes, including
      putative polymerase, helicase, ribose methyltransferase, exoribonuclease, and
      endoribonuclease activities. ORF1a encodes several membrane domains, a putative
      ADP-ribose 1"-phosphatase, and a chymotrypsin-like serine protease whose activity
      was established in this study. Comparative sequence analysis revealed that WBV
      represents a separate cluster of nidoviruses that significantly diverged from
      toroviruses and, even more, from coronaviruses, roniviruses, and arteriviruses.
      The study adds to the amazing diversity of nidoviruses and appeals for a more
      extensive characterization of nonmammalian nidoviruses to better understand the
      evolution of these largest known RNA viruses.

PMID- 16987967
TI  - Cryoelectron microscopy of protein IX-modified adenoviruses suggests a new
      position for the C terminus of protein IX.
AB  - Recombinant human adenovirus is a useful gene delivery vector for clinical gene
      therapy. Minor capsid protein IX of adenovirus has been of recent interest since
      multiple studies have shown that modifications can be made to its C terminus to
      alter viral tropism or add molecular tags and/or reporter proteins. We examined
      the structure of an engineered adenovirus displaying the enhanced green
      fluorescent protein (EGFP) fused to the C terminus of protein IX. Cryoelectron
      microscopy and reconstruction localized the C-terminal EGFP fusion between the H2
      hexon and the H4 hexon, positioned between adjacent facets, directly above the
      density previously assigned as protein IIIa. The original assignment of IIIa was
      based largely on indirect evidence, and the data presented herein support the
      reassignment of the IIIa density as protein IX.

PMID- 16987968
TI  - Entire genome of a strain of human immunodeficiency virus type 1 with a deletion
      of nef that was recovered 20 years after primary infection: large pool of
      proviruses with deletions of env.
AB  - We report the complete sequence analysis of the provirus harbored in a long-term
      nonprogressor (patient SG1) 20 years after the first infection with a human
      immunodeficiency virus type 1 strain lacking nef. The sequencing showed large
      deletions in the nef-nef and nef-U3 regions. Except for vpu, all of the other
      accessory genes were intact. The gag and pol genes did not show significant
      alterations. We found large deletions in env, spanning the V1, V2, V3, V4, and V5
      regions. We believe that, when down-regulation of the class 1 major
      histocompatibility complex molecules is inhibited by the lack of nef function,
      the cells containing Env-defective molecules evade cytotoxic T lymphocyte killing
      and accumulate progressively.

PMID- 16987969
TI  - Translational inhibition and increased interferon induction in cells infected
      with C protein-deficient measles virus.
AB  - In addition to the phosphoprotein, the P gene of measles virus (MV) also encodes
      the V and C proteins by an RNA editing process and by alternative initiation of
      translation in a different reading frame, respectively. Although the MV C protein
      is required for efficient MV replication in vivo and in some cultured cells, its
      exact functions in virus infection are currently unclear. Here, we report that a
      recombinant MV lacking the C protein (MVDeltaC) grew poorly in a human cell line
      possessing the intact interferon (IFN) pathway and that this growth defect was
      associated with reduced viral translation and genome replication. The
      translational inhibition was correlated with phosphorylation of the alpha subunit
      of eukaryotic translation initiation factor 2. Moreover, increased IFN induction
      was observed in MVDeltaC-infected cells. The NS1 protein of influenza virus,
      which binds to double-stranded RNA (dsRNA) and consequently inhibits IFN
      induction and dsRNA-dependent protein kinase activation, complemented the growth
      defect of MVDeltaC. These results indicate that the MV C protein inhibits IFN
      induction and modulates host antiviral responses, thereby ensuring MV growth in
      host cells.

PMID- 16987970
TI  - Human cytomegalovirus (HCMV) infection of endothelial cells promotes naive
      monocyte extravasation and transfer of productive virus to enhance hematogenous
      dissemination of HCMV.
AB  - Human cytomegalovirus (HCMV) pathogenesis is dependent on the hematogenous spread
      of the virus to host tissue. While data suggest that infected monocytes are
      required for viral dissemination from the blood to the host organs, infected
      endothelial cells are also thought to contribute to this key step in viral
      pathogenesis. We show here that HCMV infection of endothelial cells increased the
      recruitment and transendothelial migration of monocytes. Infection of endothelial
      cells promoted the increased surface expression of cell adhesion molecules
      (intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1, E
      selectin, and platelet endothelial cell adhesion molecule 1), which were
      necessary for the recruitment of naive monocytes to the apical surface of the
      endothelium and for the migration of these monocytes through the endothelial cell
      layer. As a mechanism to account for the increased monocyte migration, we showed
      that HCMV infection of endothelial cells increased the permeability of the
      endothelium. The cellular changes contributing to the increased permeability and
      increased naive monocyte transendothelial migration include the disruption of
      actin stress fiber formation and the decreased expression of lateral junction
      proteins (occludin and vascular endothelial cadherin). Finally, we showed that
      the migrating monocytes were productively infected with the virus, documenting
      that the virus was transferred to the migrating monocyte during passage through
      the lateral junctions. Together, our results provide evidence for an active role
      of the infected endothelium in HCMV dissemination and pathogenesis.

PMID- 16987971
TI  - Binding and nuclear relocalization of protein kinase R by human cytomegalovirus
      TRS1.
AB  - The human cytomegalovirus (HCMV) TRS1 and IRS1 genes block the phosphorylation of
      the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) and the
      consequent shutoff of cellular protein synthesis that occur during infection with
      vaccinia virus (VV) deleted of the double-stranded RNA binding protein gene E3L
      (VVDeltaE3L). To further define the underlying mechanism, we first evaluated the
      effect of pTRS1 on protein kinase R (PKR), the double-stranded RNA (dsRNA)
      dependent eIF2alpha kinase. Immunoblot analyses revealed that pTRS1 expression in
      the context of a VVDeltaE3L recombinant decreased levels of PKR in the cytoplasm
      and increased its levels in the nucleus of infected cells, an effect not seen
      with wild-type VV or a VVDeltaE3L recombinant virus expressing E3L. This effect
      of pTRS1 was confirmed by visualizing the nuclear relocalization of PKR-EGFP
      expressed by transient transfection. PKR present in both the nuclear and
      cytoplasmic fractions was nonphosphorylated, indicating that it was unactivated
      when TRS1 was present. PKR also accumulated in the nucleus during HCMV infection
      as determined by indirect immunofluorescence and immunoblot analysis. Binding
      assays revealed that pTRS1 interacted with PKR in mammalian cells and in vitro.
      This interaction required the same carboxy-terminal region of pTRS1 that is
      necessary to rescue VVDeltaE3L replication in HeLa cells. The carboxy terminus of
      pIRS1 was also required for rescue of VVDeltaE3L and for mediating an interaction
      of pIRS1 with PKR. These results suggest that these HCMV genes directly interact
      with PKR and inhibit its activation by sequestering it in the nucleus, away from
      both its activator, cytoplasmic dsRNA, and its substrate, eIF2alpha.

PMID- 16987972
TI  - Novel fiber-dependent entry mechanism for adenovirus serotype 5 in lacrimal
      acini.
AB  - The established mechanism for infection of most cells with adenovirus serotype 5
      (Ad5) involves fiber capsid protein binding to coxsackievirus-adenovirus receptor
      (CAR) at the cell surface, followed by penton base capsid protein binding to
      alpha(v) integrins, which triggers clathrin-mediated endocytosis of the virus.
      Here we determined the identity of the capsid proteins responsible for mediating
      Ad5 entry into the acinar epithelial cells of the lacrimal gland. Ad5
      transduction of primary rabbit lacrimal acinar cells was inhibited by excess Ad5
      fiber or knob (terminal region of the fiber) but not excess penton base.
      Investigation of the interactions of recombinant Ad5 penton base, fiber, and knob
      with lacrimal acini revealed that the penton base capsid protein remained surface
      associated, while the knob domain of the fiber capsid protein was rapidly
      internalized. Introduction of rabbit CAR-specific small interfering RNA (siRNA)
      into lacrimal acini under conditions that reduced intracellular CAR mRNA
      significantly inhibited Ad5 transduction, in contrast to a control (nonspecific)
      siRNA. Preincubation of Ad5 with excess heparin or pretreatment of acini with a
      heparinase cocktail each inhibited Ad5 transduction by a separate and apparently
      additive mechanism. Functional and imaging studies revealed that Ad5, fiber, and
      knob, but not penton base, stimulated macropinocytosis in acini and that
      inhibition of macropinocytosis significantly reduced Ad5 transduction of acini.
      However, inhibition of macropinocytosis did not reduce Ad5 uptake. We propose
      that internalization of Ad5 into lacrimal acini is through a novel fiber
      dependent mechanism that includes CAR and heparan sulfate glycosaminoglycans and
      that the subsequent intracellular trafficking of Ad5 is enhanced by fiber-induced
      macropinocytosis.

PMID- 16987973
TI  - A helper-dependent capsid-modified adenovirus vector expressing adeno-associated
      virus rep78 mediates site-specific integration of a 27-kilobase transgene
      cassette.
AB  - Random integration of viral gene therapy vectors and subsequent activation or
      disruption of cellular genes poses safety risks. Major efforts in the field are
      aimed toward targeting vector integration to specific sites in the host genome.
      The adeno-associated virus (AAV) Rep78 protein is able to target AAV integration
      to a specific site on human chromosome 19, called AAVS1. We studied whether this
      ability could be harnessed to achieve site-specific integration of a 27-kb
      transgene cassette into a model cell line for human hematopoietic cells (Mo7e).
      To deliver rep78 and the transgene to Mo7e cells, we used helper-dependent
      adenovirus (Ad) vectors containing Ad serotype 35 fiber knob domains (HD-Ad). An
      HD-Ad vector containing the rep78 gene under the control of the globin locus
      control region (LCR) (Ad.LCR-rep78) conferred Rep78 expression on Mo7e cells.
      Upon coinfection of Ad.LCR-rep78 with an HD-Ad vector containing a 27-kb globin
      LCR-green fluorescent protein (GFP) transgene cassette flanked by AAV inverted
      terminal repeats (ITRs) (Ad.AAV-LCR-GFP), transduced cells were cloned and
      expanded (without selection pressure), and vector integration was analyzed in
      clones with more than 30% GFP-positive cells. Vector integration into the AAVS1
      region was seen in 30% of analyzed integration sites, and GFP expression from
      these integrants was stable over time. Of the remaining integration sites, 25%
      were within the genomic globin LCR. In almost 90% of sites, transgene integration
      occurred via the Ad ITR. This indicates that rescue of the AAV ITR-flanked
      transgene cassette from Ad.AAV-LCR-GFP is not required for Rep78-mediated
      integration into AAVS1 and that free ends within the vector genome can be created
      by breaks within the Ad ITRs, whose structure is apparently recognized by
      cellular "nicking" enzymes. The finding that 55% of all analyzed integration
      sites were either within the AAVS1 or globin LCR region demonstrates that a high
      frequency of targeted integration of a large transgene cassette can be achieved
      in human hematopoietic stem cell lines.

PMID- 16987974
TI  - Evidence that the immediate-early gene product ICP4 is necessary for the genome
      of the herpes simplex virus type 1 ICP4 deletion mutant strain d120 to
      circularize in infected cells.
AB  - Following infection, the physical state of linear herpes simplex virus (HSV)
      genomes may change into an "endless" or circular form. In this study, using
      Southern blot analysis of the HSV genome, we provide evidence that immediate
      early protein ICP4 is involved in the process of converting the linear HSV-1 ICP4
      deleted mutant strain d120 genome into its endless form. Under conditions where
      de novo viral DNA synthesis was inhibited, the genome of the ICP4 deletion mutant
      d120 failed to assume an endless conformation following infection of Vero cells
      (compared with the ability of wild-type strain KOS). This defect was reversed in
      the Vero-derived cell line E5, which produces the ICP4 protein, suggesting that
      ICP4 is necessary and sufficient to complement the d120 defect. When ICP4 protein
      was provided by the replication-defective DNA polymerase mutant HP66, the genomes
      of mutant d120 could assume an endless conformation in Vero cells. Western blot
      analysis using antibody specific to the ICP4 protein showed that although the
      d120 virions contained ICP4 protein, the majority of that ICP4 protein was in a
      40-kDa truncated form, with only a small fraction present as a full-length 175
      kDa protein. When expression of ICP4 protein from E5 cells was inhibited by
      cycloheximide, the d120 virion-associated ICP4 protein was unable to mediate
      endless formation after infection of E5 cells. Collectively, these data suggest
      that ICP4 protein has an important role in mediating the endless formation of the
      HSV-1 genome upon infection and that this function can be provided in trans.

PMID- 16987975
TI  - Hemagglutinin (HA) proteins from H1 and H3 serotypes of influenza A viruses
      require different antigen designs for the induction of optimal protective
      antibody responses as studied by codon-optimized HA DNA vaccines.
AB  - Effective antibody responses provide crucial immunity against influenza virus
      infection. The hemagglutinin (HA) protein is the major target of protective
      antibody responses induced by viral infection and by vaccination with both
      inactivated and live-attenuated flu vaccines, but knowledge about the optimal
      designs of protective HA antigens from different flu serotypes is still limited.
      In this study, we have significantly improved the immunogenicity of HA-expressing
      DNA vaccines by using codon-optimized HA sequences for either an H1 serotype
      (A/NewCal/20/99) or an H3 serotype (A/Panama/2007/99) human influenza A virus and
      then used these constructs as model antigens to identify the optimal HA antigen
      designs to elicit high-level protective antibody responses. Two forms of HA
      antigen, a wild-type, full-length HA and a secreted form with transmembrane (TM)
      domain-truncated HA, were produced. Both forms of HA DNA vaccines, from either H1
      or H3 serotypes, were able to elicit high levels of HA-specific immunoglobulin G
      responses in immunized rabbits as measured by enzyme-linked immunosorbent assay.
      Interestingly, the abilities of H1 HA and H3 HA antigens to elicit
      hemagglutination inhibition (HI) and neutralizing antibody (NAb) responses
      differ. For the H1 HA antigens, the full-length HA induced significantly higher
      HI and NAb responses than did the TM-truncated HA. For the H3 HA antigen, both
      the full-length HA and TM-truncated HA induced high levels of HI and NAb
      responses. These data indicate that H1 and H3 antigens have different expression
      requirements for the induction of an optimal protective antibody response and
      that the structure integrity of HA antigens is critical for eliciting type
      specific protective antibody responses. Our findings will have an important
      impact on future subunit-based flu vaccine development.

PMID- 16987976
TI  - Autographa californica multiple nucleopolyhedrovirus nucleocapsid assembly is
      interrupted upon deletion of the 38K gene.
AB  - 38K (ac98) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a
      highly conserved baculovirus gene whose function is unknown. To determine the
      role of 38K in the baculovirus life cycle, a 38K knockout bacmid containing the
      AcMNPV genome was generated through homologous recombination in Escherichia coli.
      Furthermore, a 38K repair bacmid was constructed by transposing the 38K open
      reading frame with its native promoter region into the polyhedrin locus of the
      38K knockout bacmid. After transfection of these viruses into Spodoptera
      frugiperda cells, the 38K knockout bacmid led to a defect in production of
      infectious budded virus, while the 38K repair bacmid rescued this defect,
      allowing budded-virus titers to reach wild-type levels. Slot blot analysis
      indicated that 38K deletion did not affect the levels of viral DNA replication.
      Subsequent immunoelectron-microscopic analysis revealed that masses of electron
      lucent tubular structures containing the capsid protein VP39 were present in
      cells transfected with 38K knockout bacmids, suggesting that nucleocapsid
      assembly was interrupted. In contrast, the production of normal nucleocapsids was
      restored when the 38K knockout bacmid was rescued with a copy of 38K. Recombinant
      virus that expresses 38K fused to green fluorescent protein as a visual marker
      was constructed to monitor protein transport and localization within the nucleus
      during infection. Fluorescence was first detected along the cytoplasmic periphery
      of the nucleus and subsequently localized to the center of the nucleus. These
      results demonstrate that 38K plays a role in nucleocapsid assembly and is
      essential for viral replication in the AcMNPV life cycle.

PMID- 16987977
TI  - Comparison of avian and human influenza A viruses reveals a mutational bias on
      the viral genomes.
AB  - In the last few years, the genomic sequence data for thousands of influenza A
      virus strains, including the 1918 pandemic strain, and hundreds of isolates of
      the avian influenza virus H5N1, which is causing an increasing number of human
      fatalities, have become publicly available. This large quantity of sequence data
      allows us to do comparative genomics with the human and avian versions of the
      virus. We find that the nucleotide compositions of influenza A viruses infecting
      the two hosts are sufficiently different that we can determine the host at almost
      100% accuracy. This assignment works at the segment level, which allows us to
      construct the reassortment history of individual segments within each strain. We
      suggest that the different nucleotide compositions can be explained by a host
      dependent mutation bias. To support this idea, we estimate the fixation rates for
      the different polymerase segments and the ratios of synonymous to nonsynonymous
      changes. Additionally, we provide evidence supporting the hypothesis that the
      H1N1 influenza virus entered the human population just prior to the 1918
      outbreak, with an earliest bound of 1910.

PMID- 16987978
TI  - The Epstein-Barr virus-encoded LMP-1 oncoprotein negatively affects Tyk2
      phosphorylation and interferon signaling in human B cells.
AB  - Epstein-Barr virus (EBV) establishes a persistent infection in the human host and
      is associated with a variety of human cancers. Persistent infection results from
      a balance between the host immune response and viral immune evasion mechanisms.
      EBV infection is controlled initially by the innate immune response and later by
      T-cell-mediated adaptive immunity. EBV has evolved mechanisms to evade the host
      immune response so that it can persist for the lifetime of the host. Latent
      membrane protein 1 (LMP-1) is the EBV oncoprotein essential for B-cell
      immortalization by EBV. We show here that LMP-1 interacts with Tyk2, a signaling
      intermediate in the alpha interferon (IFN-alpha) signaling pathway, via a
      previously uncharacterized LMP-1 signaling domain. LMP-1 prevents Tyk2
      phosphorylation and inhibits IFN-alpha-stimulated STAT2 nuclear translocation and
      interferon-stimulated response element transcriptional activity. Long-term
      culture of EBV+ lymphoblastoid cells in IFN-alpha is associated with outgrowth of
      a population expressing elevated LMP-1 protein levels, suggesting that cells
      expressing higher levels of LMP-1 survive the antiproliferative selective
      pressure imposed by IFN-alpha. These results show that LMP-1 can protect EBV+
      cells from the IFN-alpha-stimulated antiviral/antiproliferative response and
      suggest that chronic IFN-alpha treatment may encourage the outgrowth of cells
      expressing elevated, and therefore potentially oncogenic, LMP-1 levels in EBV+
      individuals.

PMID- 16987979
TI  - Epstein-Barr virus selectively deregulates DNA damage responses in normal B cells
      but has no detectable effect on regulation of the tumor suppressor p53.
AB  - To determine whether latent Epstein-Barr virus (EBV) modifies DNA damage
      responses in B lymphocytes, cells were treated with agents either producing DNA
      cross-links and adducts or generating double-strand breaks. The cyclin-dependent
      kinase inhibitor p21(WAF1) accumulated in mitogen-stimulated primary B cells
      following exposure to all genotoxins tested. In contrast, when proliferation was
      EBV driven, p21(WAF1) failed to accumulate after treatment with the DNA adduct
      producing agents. The tumor suppressor p53 was stabilized and phosphorylated
      after all treatments, irrespective of whether latent EBV was present. This
      suggests that regulatory pathways upstream of p53 are unaffected by latent EBV
      but downstream effectors are altered if DNA adducts or distortions are involved.

PMID- 16987980
TI  - Genomic sequence of Spodoptera frugiperda Ascovirus 1a, an enveloped, double
      stranded DNA insect virus that manipulates apoptosis for viral reproduction.
AB  - Ascoviruses (family Ascoviridae) are double-stranded DNA viruses with circular
      genomes that attack lepidopterans, where they produce large, enveloped virions,
      150 by 400 nm, and cause a chronic, fatal disease with a cytopathology resembling
      that of apoptosis. After infection, host cell DNA is degraded, the nucleus
      fragments, and the cell then cleaves into large virion-containing vesicles. These
      vesicles and virions circulate in the hemolymph, where they are acquired by
      parasitic wasps during oviposition and subsequently transmitted to new hosts. To
      develop a better understanding of ascovirus biology, we sequenced the genome of
      the type species Spodoptera frugiperda ascovirus 1a (SfAV-1a). The genome
      consisted of 156,922 bp, with a G+C ratio of 49.2%, and contained 123 putative
      open reading frames coding for a variety of enzymes and virion structural
      proteins, of which tentative functions were assigned to 44. Among the most
      interesting enzymes, due to their potential role in apoptosis and viral vesicle
      formation, were a caspase, a cathepsin B, several kinases, E3 ubiquitin ligases,
      and especially several enzymes involved in lipid metabolism, including a fatty
      acid elongase, a sphingomyelinase, a phosphate acyltransferase, and a patatin
      like phospholipase. Comparison of SfAV-1a proteins with those of other viruses
      showed that 10% were orthologs of Chilo iridescent virus proteins, the highest
      correspondence with any virus, providing further evidence that ascoviruses
      evolved from a lepidopteran iridovirus. The SfAV-1a genome sequence will
      facilitate the determination of how ascoviruses manipulate apoptosis to generate
      the novel virion-containing vesicles characteristic of these viruses and enable
      study of their origin and evolution.

PMID- 16987981
TI  - Flavivirus infection activates the XBP1 pathway of the unfolded protein response
      to cope with endoplasmic reticulum stress.
AB  - The unfolded protein response (UPR) is a coordinated change in gene expression
      triggered by perturbations in functions of the endoplasmic reticulum (ER). XBP1,
      a key transcription factor of the UPR, is activated by an IRE1-mediated splicing
      event, which results in a frameshift and encodes a protein with transcriptional
      activity. Here, we report that XBP1 was activated during flaviviral infection, as
      evidenced by XBP1 mRNA splicing and protein expression, as well as induction of
      the downstream genes ERdj4, EDEM1, and p58(IPK) in Japanese encephalitis virus
      (JEV)- and dengue virus serotype 2 (DEN-2)-infected cells. Reporter systems based
      on IRE1-mediated XBP1 splicing were established, and several flaviviral proteins
      associated with the ER, including glycoproteins and small hydrophobic membrane
      anchored proteins, were found to trigger the splicing event. Notably,
      nonstructural protein NS2B-3 of DEN-2, but not of JEV, was a potent inducer of
      XBP1 splicing through an unclear mechanism(s). Reduction of XBP1 by a small
      interfering RNA had no effect on cells' susceptibility to the two viruses but
      exacerbated the flavivirus-induced cytopathic effects. Overall, flaviviruses
      trigger the XBP1 signaling pathway and take advantage of this cellular response
      to alleviate virus-induced cytotoxicity.

PMID- 16987982
TI  - Nuclear export of simian immunodeficiency virus Vpx protein.
AB  - Lentiviruses, human immunodeficiency viruses (HIVs), and simian immunodeficiency
      viruses (SIVs) are distinguished from oncoretroviruses by their ability to infect
      nondividing cells such as macrophages. Retroviruses must gain access to the host
      cell nucleus for replication and propagation. HIV and SIV preintegration
      complexes (PIC) enter nuclei after traversing the central aqueous channel of the
      limiting nuclear pore complex without membrane breakdown. Among the nucleophilic
      proteins, namely, matrix, integrase, Vpx, and Vpr, present in HIV type 2/SIV PIC,
      Vpx is implicated in nuclear targeting and is also available for incorporation
      into budding virions at the plasma membrane. The mechanisms of these two opposite
      functions are not known. We demonstrate that Vpx is a nucleocytoplasmic shuttling
      protein and contains two novel noncanonical nuclear import signals and a
      leptomycin B-sensitive nuclear export signal. In addition, Vpx interacts with the
      cellular tyrosine kinase Fyn through its C-terminal proline-rich motif.
      Furthermore, our data indicate that Fyn kinase phosphorylates Vpx and regulates
      its export from nucleus. Replacement of conserved tryptophan residues within
      domain 41 to 63 and tyrosine residues at positions 66, 69, and 71 in Vpx impairs
      its nuclear export, virion incorporation, and SIV replication in macrophages.
      Nuclear export is essential to ensure the availability of Vpx in the cytoplasm
      for incorporation into virions, leading to efficient viral replication within
      nondividing cells.

PMID- 16987983
TI  - A trans-Golgi network resident protein, golgin-97, accumulates in viral factories
      and incorporates into virions during poxvirus infection.
AB  - Poxviruses are the only DNA viruses known to replicate and assemble in the
      cytoplasm of infected cells. Poxvirus morphogenesis is a complicated process in
      which four distinct infectious forms of the virus are produced: intracellular
      mature virus, intracellular enveloped virus, cell-associated enveloped virus, and
      extracellular enveloped virus. The source of primary membrane wrapping the
      intracellular mature virus, the first infectious form, is still unknown. Although
      the membrane was suggested to originate from the endoplasmic reticulum-Golgi
      intermediate compartment, none of the marker proteins from this or any other cell
      compartments has been found in the intracellular mature virus. Thus, it was
      hypothesized that the membrane is either extensively modified by the virus or
      synthesized de novo. In the work described here, we demonstrate that a host cell
      protein residing in the trans-Golgi network membrane, golgin-97, is transported
      to the sites of virus replication and assembly and becomes incorporated into the
      virions during poxvirus infection. Inside the virion, golgin-97 is associated
      with the insoluble core protein fraction. Being able to adopt a long rod-like
      structure, the protein apparently extends through the virion envelope and
      protrudes from its surface. Here we discuss the potential role and functions of
      golgin-97 in poxvirus replication and propose two working models.

PMID- 16987984
TI  - Double-stranded RNA binding of influenza B virus nonstructural NS1 protein
      inhibits protein kinase R but is not essential to antagonize production of
      alpha/beta interferon.
AB  - Expression of alpha/beta interferon (IFN-alpha/beta) in virus-infected vertebrate
      cells is a key event in the establishment of a sustained antiviral response,
      which is triggered by double-stranded RNA (dsRNA) produced during viral
      replication. These antiviral cytokines initiate the expression of cellular
      proteins with activities that limit the replication and spread of the invading
      viruses. Within this response, the dsRNA-dependent protein kinase R (PKR) that is
      expressed at constitutive levels and upregulated by IFN-alpha/beta acts as an
      important antiviral effector that can block the cellular translational machinery.
      We previously demonstrated that efficient replication of influenza B virus
      depends on the viral dsRNA-binding NS1 protein that inhibits the transcriptional
      activation of IFN-alpha/beta genes. Here we tested the postulate that the viral
      NS1 protein counteracts antiviral responses through sequestering intracellular
      dsRNA by analyzing a collection of recombinant influenza B viruses. As expected,
      viruses expressing dsRNA-binding-defective NS1 proteins were strongly attenuated
      for replication in IFN-competent hosts. Interestingly, these virus mutants failed
      to prevent activation of PKR but could effectively limit IFN induction.
      Conversely, a mutant virus expressing the N-terminal dsRNA-binding domain of NS1
      prevented PKR activation, but not IFN induction, suggesting an important role for
      the NS1 C-terminal part in silencing the activation route of IFN-alpha/beta
      genes. Thus, our findings indicate an unexpected mechanistic dichotomy of the
      influenza B virus NS1 protein in the suppression of antiviral responses, which
      involves at least one activity that is largely separable from dsRNA binding.

PMID- 16987985
TI  - Crystal structure of the West Nile virus envelope glycoprotein.
AB  - The envelope glycoprotein (E) of West Nile virus (WNV) undergoes a conformational
      rearrangement triggered by low pH that results in a class II fusion event
      required for viral entry. Herein we present the 3.0-A crystal structure of the
      ectodomain of WNV E, which reveals insights into the flavivirus life cycle. We
      found that WNV E adopts a three-domain architecture that is shared by the E
      proteins from dengue and tick-borne encephalitis viruses and forms a rod-shaped
      configuration similar to that observed in immature flavivirus particles.
      Interestingly, the single N-linked glycosylation site on WNV E is displaced by a
      novel alpha-helix, which could potentially alter lectin-mediated attachment. The
      localization of histidines within the hinge regions of E implicates these
      residues in pH-induced conformational transitions. Most strikingly, the WNV E
      ectodomain crystallized as a monomer, in contrast to other flavivirus E proteins,
      which have crystallized as antiparallel dimers. WNV E assembles in a crystalline
      lattice of perpendicular molecules, with the fusion loop of one E protein buried
      in a hydrophobic pocket at the DI-DIII interface of another. Dimeric E proteins
      pack their fusion loops into analogous pockets at the dimer interface. We
      speculate that E proteins could pivot around the fusion loop-pocket junction,
      allowing virion conformational transitions while minimizing fusion loop exposure.

PMID- 16987986
TI  - Overexpression of the lens epithelium-derived growth factor/p75 integrase binding
      domain inhibits human immunodeficiency virus replication.
AB  - We initially identified lens epithelium-derived growth factor/p75 (LEDGF/p75) as
      a binding partner of human immunodeficiency virus type 1 (HIV-1) integrase. To
      investigate the role of LEDGF/p75 in HIV replication and its potential as a new
      antiviral target, we stably overexpressed two different fragments containing the
      integrase binding domain (IBD) of LEDGF/p75 fused to enhanced green fluorescent
      protein (eGFP). HIV-1 replication was severely inhibited by overexpression of the
      eGFP-IBD fusion proteins, while no inhibition was observed in cell lines
      overexpressing the interaction-deficient D366A mutant. Quantitative PCR
      pinpointed the block to the integration step, whereas nuclear import was not
      affected. Competition of the IBD fusion proteins with endogenous LEDGF/p75 for
      binding to integrase led to a potent defect in HIV-1 replication in both HeLaP4-
      and MT-4-derived cell lines. A previously described diketo acid-resistant HIV-1
      strain remained fully susceptible to inhibition, suggesting that this strategy
      will also work in patients who harbor strains resistant to the current
      experimental integrase inhibitors. These data support LEDGF/p75 as an important
      cofactor for HIV replication and provide proof of concept for the LEDGF/p75
      integrase interaction as a novel target for treating HIV-1 infection.

PMID- 16987987
TI  - Inhibition of coxsackievirus B3 in cell cultures and in mice by peptide
      conjugated morpholino oligomers targeting the internal ribosome entry site.
AB  - Coxsackievirus B3 (CVB3) is a primary cause of viral myocarditis, yet no
      effective therapeutic against CVB3 is available. Nucleic acid-based
      interventional strategies against various viruses, including CVB3, have shown
      promise experimentally, but limited stability and inefficient delivery in vivo
      remain as obstacles to their potential as therapeutics. We employed
      phosphorodiamidate morpholino oligomers (PMO) conjugated to a cell-penetrating
      arginine-rich peptide, P007 (to form PPMO), to address these issues. Eight CVB3
      specific PPMO were evaluated with HeLa cells and HL-1 cardiomyocytes in culture
      and in a murine infection model. One of the PPMO (PPMO-6), designed to target a
      sequence in the 3' portion of the CVB3 internal ribosomal entry site, was found
      to be especially potent against CVB3. Treatment of cells with PPMO-6 prior to
      CVB3 infection produced an approximately 3-log(10) decrease in viral titer and
      largely protected cells from a virus-induced cytopathic effect. A similar
      antiviral effect was observed when PPMO-6 treatment began shortly after the virus
      infection period. A/J mice receiving intravenous administration of PPMO-6 once
      prior to and once after CVB3 infection showed an approximately 2-log(10)
      decreased viral titer in the myocardium at 7 days postinfection and a
      significantly decreased level of cardiac tissue damage, compared to the controls.
      Thus, PPMO-6 provided potent inhibition of CVB3 amplification both in cell
      cultures and in vivo and appears worthy of further evaluation as a candidate for
      clinical development.

PMID- 16987988
TI  - siRNA knock down of casein kinase 2 increases force and cross-bridge cycling
      rates in vascular smooth muscle.
AB  - Contraction of smooth muscle involves myosin light chain (MLC) kinase catalyzed
      phosphorylation of the regulatory MLC, activation of myosin, and the development
      of force. However, this cannot account for all aspects of a smooth muscle
      contraction, suggesting that other regulatory mechanisms exist. One potentially
      important technique to study alternative sites of contractile regulation is the
      use of small interfering RNA (siRNA). The goal of this study was to determine
      whether siRNA technology can decrease the levels of a specific protein and allow
      for the determination of how that protein affects contractile regulation. To
      achieve this goal, we tested the hypothesis that casein kinase 2 (CK2) is part of
      the complex regulatory scheme present in vascular smooth muscle. Using intact
      strips of swine carotid artery, we determined that siRNA against CK2 produced a
      tissue that resulted in a approximately 60% knockdown after 4 days in organ
      culture. Intact strips of vascular tissue depleted of CK2 produced greater levels
      of force and exhibited an increased sensitivity to all stimuli tested. This was
      accompanied by an increase in cross-bridge cycling rates but not by a change in
      MLC phosphorylation levels. alpha-Toxin-permeabilized vascular tissue depleted of
      CK2 also showed an increased sensitivity to calcium compared with control
      tissues. Our results demonstrate that siRNA is a viable technique with which to
      study regulatory pathways in intact smooth muscle tissue. Our results also
      demonstrate that CK2 plays an important role in the mechanism(s) responsible for
      the development of force and cross-bridge cycling by a MLC phosphorylation
      independent pathway.

PMID- 16987989
TI  - Cytokine expression and AIF-1-mediated activation of Rac2 in vascular smooth
      muscle cells: a role for Rac2 in VSMC activation.
AB  - Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic, calcium-binding,
      inflammation-responsive scaffold protein involved in vascular smooth muscle cell
      (VSMC) migration and proliferation. The objective of this study is to
      characterize AIF-1 functional protein interactions that may regulate VSMC
      activation. Through use of a bacterial two-hybrid screen, we identified a
      molecular interaction between AIF-1 and the small GTPase, Rac2, which was
      verified by pull-down and colocalization experiments. This was unexpected in that
      Rac2 expression had been considered to be restricted to hematopoietic cells. The
      Rac2/AIF-1 interaction is functional, in that a loss-of-function, point-mutated
      AIF-1 does not interact with Rac2; Rac2 colocalizes with AIF-1 in the cytoplasm
      of VSMC and cotranslocates to lamellopodia upon platelet-derived growth factor
      stimulation; and AIF-1 expression in VSMC leads to Rac2 activation. Because Rac2
      function in VSMC had not been described, we focused on characterization of its
      function in these cells. Rac2 protein expression in VSMC is inducible by
      inflammatory cytokines, and Rac2 activation in VSMC is also responsive to
      inflammatory cytokines. Rac2 expression and activation patterns differ from the
      ubiquitously expressed Rac1. We hypothesized that Rac2 participates in VSMC
      activation. Retroviral overexpression of Rac2 in primary VSMC leads to increased
      migration, activation of the NADPH oxidation cascade, and increased activation of
      the Rac2 effector protein Pak1 and its proximal effectors, ERK1/2, and p38 (P <
      0.05 for all). The major points of this study indicate a functional interaction
      between AIF-1 and Rac2 in VSMC leading to Rac2 activation and a potential
      function for Rac2 in inflammation-driven VSMC response to injury.

PMID- 16987990
TI  - Proximal tubular epithelial cells are generated by division of differentiated
      cells in the healthy kidney.
AB  - We searched for evidence for a contribution of stem cells in growth of the
      proximal S3 segments of healthy rats. According to the stem cell model, stem
      cells are undifferentiated and slow cycling; the bulk of cycling cells are
      transit amplifying, rapidly cycling cells. We show the following. 1) By
      continuous application of a thymidine analog (ThA) for 7 days, S3 proximal
      epithelial cells in healthy kidneys display a high-cycling rate. 2) Slow-cycling
      cells, identified by lack of ThA uptake during 14 days of continuous ThA
      application up to death and by expression of the cell cycle protein Ki67 at
      death, have the same degree of differentiation as quiescent cells. 3) To detect
      rapidly cycling cells, rats were killed at various time points after injection of
      a ThA. Double immunofluorescence for ThA and a cell cycle marker was performed,
      with colocalization indicating successive divisions. During one week after
      division, daughter cells display a very low proliferation rate, indicating the
      absence of rapidly cycling cells. 4) Labeling with cyclin D1 showed that this low
      proliferation rate is due to cycle arrest. 5) More than 50% of the S3 cells
      entered the cell cycle 36 h after a potent proliferative stimulus (lead acetate
      injection). We conclude that generation of new cells in the proximal tubule
      relies on division of differentiated, normally slow-cycling cells. These may
      rapidly enter the cycle under an adequate stimulus.

PMID- 16987991
TI  - Cell-based imaging of sodium iodide symporter activity with the yellow
      fluorescent protein variant YFP-H148Q/I152L.
AB  - The sodium iodide symporter (NIS) mediates iodide (I(-)) transport in the thyroid
      gland and other tissues and is of increasing importance as a therapeutic target
      and nuclear imaging reporter. NIS activity in vitro is currently measured with
      radiotracers and electrophysiological techniques. We report on the development of
      a novel live cell imaging assay of NIS activity using the I(-)-sensitive and
      genetically encodable yellow fluorescent protein (YFP) variant YFP-H148Q/I152L.
      In FRTL-5 thyrocytes stably expressing YFP-H148Q/I152L, I(-) induced a rapid and
      reversible decrease in cellular fluorescence characterized by 1) high affinity
      for extracellular I(-) (35 muM), 2) inhibition by the NIS inhibitor perchlorate,
      3) extracellular Na(+) dependence, and 4) TSH dependence, suggesting that
      fluorescence changes are due to I(-) influx via NIS. Individual cells within a
      population of FRTL-5 cells exhibited a 3.5-fold variation in the rate of NIS
      mediated I(-) influx, illustrating the utility of YFP-H148Q/I152L to detect cell
      to-cell difference in NIS activity. I(-) also caused a perchlorate-sensitive
      decrease in YFP-H148Q/I152L fluorescence in COS-7 cells expressing NIS but not in
      cells lacking NIS. These results demonstrate that YFP-H148Q/I152L is a sensitive
      biosensor of NIS-mediated I(-) uptake in thyroid cells and in nonthyroidal cells
      following gene transfer and suggest that fluorescence detection of cellular I(-)
      may be a useful tool by which to study the pathophysiology and pharmacology of
      NIS.

PMID- 16987992
TI  - Treatment of cultured myotubes with the proteasome inhibitor beta-lactone
      increases the expression of the transcription factor C/EBPbeta.
AB  - The role of the proteasome in the regulation of cellular levels of the
      transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) is poorly
      understood. We tested the hypothesis that C/EBPbeta levels in cultured myotubes
      are regulated, at least in part, by proteasome activity. Treatment of cultured L6
      myotubes, a rat skeletal muscle cell line, with the specific proteasome inhibitor
      beta-lactone resulted in increased nuclear levels of C/EBPbeta as determined by
      Western blotting and immunofluorescent detection. This effect of beta-lactone
      reflected inhibited degradation of C/EBPbeta. Surprisingly, the increased
      C/EBPbeta levels in beta-lactone-treated myotubes did not result in increased DNA
      binding activity. In additional experiments, treatment of the myotubes with beta
      lactone resulted in increased nuclear levels of growth arrest DNA damage/C/EBP
      homologous protein (Gadd153/CHOP), a dominant-negative member of the C/EBP family
      that can form heterodimers with other members of the C/EBP family and block DNA
      binding. Coimmunoprecipitation and immunofluorescent detection provided evidence
      that C/EBPbeta and Gadd153/CHOP interacted and colocalized in the nuclei of the
      beta-lactone-treated myotubes. When Gadd153/CHOP expression was downregulated by
      transfection of myotubes with siRNA targeting Gadd153/CHOP, C/EBPbeta DNA-binding
      activity was restored in beta-lactone-treated myotubes. The results suggest that
      C/EBPbeta is degraded by a proteasome-dependent mechanism in skeletal muscle
      cells and that Gadd153/CHOP can interact with C/EBPbeta and block its DNA-binding
      activity. The observations are important because they increase the understanding
      of the complex regulation of the expression and activity of C/EBPbeta in skeletal
      muscle.

PMID- 16987993
TI  - Epigenetic regulation of integrin-linked kinase expression depending on adhesion
      of gastric carcinoma cells.
AB  - Cell adhesion to the extracellular matrix (ECM) regulates gene expressions in
      diverse dynamic environments. However, the manner in which gene expressions are
      regulated by extracellular cues is largely unknown. In this study, suspended
      gastric carcinoma cells showed higher basal and transforming growth factor-beta1
      (TGFbeta1)-mediated acetylations of histone 3 (H3) and Lys(9) of H3 and levels of
      integrin-linked kinase (ILK) mRNA and protein than did fibronectin-adherent cells
      did. Moreover, the insignificant acetylation and ILK expression in adherent cells
      were recovered by alterations of integrin signaling and actin organization,
      indicating a connection between cytoplasmic and nuclear changes. Higher
      acetylations in suspended cells were correlated with associations between Smad4,
      p300/CBP, and Lys(9)-acetylated H3. Meanwhile, adherent cells showed more
      associations between HDAC3, Ski, and MeCP2. Chromatin immunoprecipitations with
      anti-acetylated H3, Lys(9)-acetylated H3, or p300/CBP antibody resulted in more
      coprecipitated ILK promoter, correlated with enhanced ILK mRNA and protein
      levels, in suspended cells. Moreover, ILK expression inversely regulated cell
      adhesion to ECM proteins, and its overexpression enhanced cell growth in soft
      agar. These observations indicate that cell adhesion and/or its related molecular
      basis regulate epigenetic mechanisms leading to a loss of ILK transcription,
      which in turn regulates cell adhesion property in a feedback linkage.

PMID- 16987994
TI  - Interleukin-1beta increases expression and activity of matrix metalloproteinase-2
      in cardiac microvascular endothelial cells: role of PKCalpha/beta1 and MAPKs.
AB  - Matrix metalloproteinases (MMPs), a family of extracellular endopeptidases, are
      implicated in angiogenesis because of their ability to selectively degrade
      components of the extracellular matrix. Interleukin-1beta (IL-1beta), increased
      in the heart post-myocardial infarction (post-MI), plays a protective role in the
      pathophysiology of left ventricular (LV) remodeling following MI. Here we studied
      expression of various angiogenic genes affected by IL-1beta in cardiac
      microvascular endothelial cells (CMECs) and investigated the signaling pathways
      involved in the regulation of MMP-2. cDNA array analysis of 96 angiogenesis
      related genes indicated that IL-1beta modulates the expression of numerous genes,
      notably increasing the expression of MMP-2, not MMP-9. RT-PCR and Western blot
      analyses confirmed increased expression of MMP-2 in response to IL-1beta. Gelatin
      in-gel zymography and Biotrak activity assay demonstrated that IL-1beta increases
      MMP-2 activity in the conditioned media. IL-1beta activated ERK1/2, JNKs, and
      protein kinase C (PKC), specifically PKCalpha/beta(1), and inhibition of these
      cascades partially inhibited IL-1beta-stimulated increases in MMP-2. Inhibition
      of PKCalpha/beta(1) failed to inhibit ERK1/2. However, concurrent inhibition of
      PKCalpha/beta(1) and ERK1/2 almost completely inhibited IL-1beta-mediated
      increases in MMP-2 expression. Inhibition of p38 kinase and nuclear factor-kappaB
      (NF-kappaB) had no effect. Pretreatment with superoxide dismutase (SOD) mimetic,
      MnTMPyP, increased MMP-2 protein levels, whereas pretreatment with SOD and
      catalase mimetic, EUK134, partially inhibited IL-1beta-stimulated increases in
      MMP-2 protein levels. Exogenous H(2)O(2) significantly increased MMP-2 protein
      levels, whereas superoxide generation by xanthine/xanthine oxidase had no effect.
      This in vitro study suggests that IL-1beta modulates expression and activity of
      MMP-2 in CMECs.

PMID- 16987995
TI  - Defective coupling of apical PTH receptors to phospholipase C prevents
      internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient
      mice.
AB  - Phosphate reabsorption in the renal proximal tubule occurs mostly via the type
      IIa Na(+)-phosphate cotransporter (NaP(i)-IIa) in the brush border membrane
      (BBM). The activity and localization of NaP(i)-IIa are regulated, among other
      factors, by parathyroid hormone (PTH). NaP(i)-IIa interacts in vitro via its last
      three COOH-terminal amino acids with the PDZ protein Na(+)/H(+)-exchanger isoform
      3 regulatory factor (NHERF)-1 (NHERF1). Renal phosphate reabsorption in Nherf1
      deficient mice is altered, and NaP(i)-IIa expression in the BBM is reduced. In
      addition, it has been proposed that NHERF1 and NHERF2 are important for the
      coupling of PTH receptors (PTHRs) to phospholipase C (PLC) and the activation of
      the protein kinase C pathway. We tested the role of NHERF1 in the regulation of
      NaP(i)-IIa by PTH in Nherf1-deficient mice. Immunohistochemistry and Western
      blotting demonstrated that stimulation of apical and basolateral receptors with
      PTH-(1-34) led to internalization of NaP(i)-IIa in wild-type and Nherf1-deficient
      mice. Stimulation of only apical receptors with PTH-(3-34) failed to induce
      internalization in Nherf1-deficient mice. Expression and localization of apical
      PTHRs were similar in wild-type and Nherf1-deficient mice. Activation of the
      protein kinase C- and A-dependent pathways with 1,2-dioctanoyl-sn-glycerol or 8
      bromo-cAMP induced normal internalization of NaP(i)-IIa in wild-type, as well as
      Nherf1-deficient, mice. Stimulation of PLC activity due to apical PTHRs was
      impaired in Nherf1-deficient mice. These data suggest that NHERF1 in the proximal
      tubule is important for PTH-induced internalization of NaP(i)-IIa and,
      specifically, couples the apical PTHR to PLC.

PMID- 16987996
TI  - Endoplasmic reticulum stress and the unfolded protein response regulate genomic
      cystic fibrosis transmembrane conductance regulator expression.
AB  - The unfolded protein response (UPR) is a cellular recovery mechanism activated by
      endoplasmic reticulum (ER) stress. The UPR is coordinated with the ER-associated
      degradation (ERAD) to regulate the protein load at the ER. In the present study,
      we tested how membrane protein biogenesis is regulated through the UPR in
      epithelia, using the cystic fibrosis transmembrane conductance regulator (CFTR)
      as a model. Pharmacological methods such as proteasome inhibition and treatment
      with brefeldin A and tunicamycin were used to induce ER stress and activate the
      UPR as monitored by increased levels of spliced XBP1 and BiP mRNA. The results
      indicate that activation of the UPR is followed by a significant decrease in
      genomic CFTR mRNA levels without significant changes in the mRNA levels of
      another membrane protein, the transferrin receptor. We also tested whether
      overexpression of a wild-type CFTR transgene in epithelia expressing endogenous
      wild-type CFTR activated the UPR. Although CFTR maturation is inefficient in this
      setting, the UPR was not activated. However, pharmacological induction of ER
      stress in these cells also led to decreased endogenous CFTR mRNA levels without
      affecting recombinant CFTR message levels. These results demonstrate that under
      ER stress conditions, endogenous CFTR biogenesis is regulated by the UPR through
      alterations in mRNA levels and posttranslationally by ERAD, whereas recombinant
      CFTR expression is regulated only by ERAD.

PMID- 16987997
TI  - Bidirectional Ca2+ coupling of mitochondria with the endoplasmic reticulum and
      regulation of multimodal Ca2+ entries in rat brown adipocytes.
AB  - How the endoplasmic reticulum (ER) and mitochondria communicate with each other
      and how they regulate plasmalemmal Ca(2+) entry were studied in cultured rat
      brown adipocytes. Cytoplasmic Ca(2+) or Mg(2+) and mitochondrial membrane
      potential were measured by fluorometry. The sustained component of rises in
      cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) produced by thapsigargin was
      abolished by removing extracellular Ca(2+), depressed by depleting extracellular
      Na(+), and enhanced by raising extracellular pH. FCCP, dinitrophenol, and
      rotenone caused bi- or triphasic rises in [Ca(2+)](i), in which the first phase
      was accompanied by mitochondrial depolarization. The FCCP-induced first phase was
      partially inhibited by oligomycin but not by ruthenium red, cyclosporine A, U
      73122, a Ca(2+)-free EGTA solution, and an Na(+)-free solution. The FCCP-induced
      second phase paralleling mitochondrial repolarization was partially blocked by
      removing extracellular Ca(2+) and fully blocked by oligomycin but not by
      thapsigargin or an Na(+)-deficient solution, was accompanied by a rise in
      cytoplasmic Mg(2+) concentration, and was summated with a high pH-induced rise in
      [Ca(2+)](i), whereas the extracellular Ca(2+)-independent component was blocked
      by U-73122 and cyclopiazonic acid. The FCCP-induced third phase was blocked by
      removing Ca(2+) but not by thapsigargin, depressed by decreasing Na(+), and
      enhanced by raising pH. Cyclopiazonic acid-evoked rises in [Ca(2+)](i) in a
      Ca(2+)-free solution were depressed after FCCP actions. Thus mitochondrial
      uncoupling causes Ca(2+) release, activating Ca(2+) release from the ER and store
      operated Ca(2+) entry, and directly elicits a novel plasmalemmal Ca(2+) entry,
      whereas Ca(2+) release from the ER activates Ca(2+) accumulation in, or release
      from, mitochondria, indicating bidirectional mitochondria-ER couplings in rat
      brown adipocytes.

PMID- 16987998
TI  - Platelet-derived growth factor-BB represses smooth muscle cell marker genes via
      changes in binding of MKL factors and histone deacetylases to their promoters.
AB  - A hallmark of smooth muscle cell (SMC) phenotypic switching is suppression of SMC
      marker gene expression. Although myocardin has been shown to be a key regulator
      of this process, the role of its related factors, MKL1 and MKL2, in SMC
      phenotypic switching remains unknown. The present studies were aimed at
      determining if: 1) MKL factors contribute to the expression of SMC marker genes
      in cultured SMCs; and 2) platelet-derived growth factor-BB (PDGF-BB)-induced
      repression of SMC marker genes is mediated by suppression of MKL factors. Results
      of gain- and loss-of-function experiments showed that MKL factors regulated the
      expression of single and multiple CArG [CC(AT-rich)(6)GG]-containing SMC marker
      genes, such as smooth muscle (SM) alpha-actin and telokin, but not CArG
      independent SMC marker genes such as smoothelin-B. Treatment with PDGF-BB reduced
      the expression of CArG-containing SMC marker genes, as well as myocardin
      expression in cultured SMCs, while it had no effect on expression of MKL1 and
      MKL2. However, of interest, PDGF-BB induced the dissociation of MKL factors from
      the CArG-containing region of SMC marker genes, as determined by chromatin
      immunoprecipitation assays. This dissociation was caused by the competition
      between MKL factors and phosphorylated Elk-1 at early time points, but
      subsequently by the reduction in acetylated histone H4 levels at these promoter
      regions mediated by histone deacetylases, HDAC2, HDAC4, and HDAC5. Results
      provide novel evidence that PDGF-BB-induced repression of SMC marker genes is
      mediated through combinatorial mechanisms, including downregulation of myocardin
      expression and inhibition of the association of myocardin/MKL factors with CArG
      containing SMC marker gene promoters.

PMID- 16987999
TI  - Action of epoxyeicosatrienoic acids on cellular function.
AB  - Epoxyeicosatrienoic acids (EETs), which function primarily as autocrine and
      paracrine mediators in the cardiovascular and renal systems, are synthesized from
      arachidonic acid by cytochrome P-450 epoxygenases. They activate smooth muscle
      large-conductance Ca(2+)-activated K(+) channels, producing hyperpolarization and
      vasorelaxation. EETs also have anti-inflammatory effects in the vasculature and
      kidney, stimulate angiogenesis, and have mitogenic effects in the kidney. Many of
      the functional effects of EETs occur through activation of signal transduction
      pathways and modulation of gene expression, events probably initiated by binding
      to a putative cell surface EET receptor. However, EETs are rapidly taken up by
      cells and are incorporated into and released from phospholipids, suggesting that
      some functional effects may occur through a direct interaction between the EET
      and an intracellular effector system. In this regard, EETs and several of their
      metabolites activate peroxisome proliferator-activated receptor alpha (PPARalpha)
      and PPARgamma, suggesting that some functional effects may result from PPAR
      activation. EETs are metabolized primarily by conversion to
      dihydroxyeicosatrienoic acids (DHETs), a reaction catalyzed by soluble epoxide
      hydrolase (sEH). Many potentially beneficial actions of EETs are attenuated upon
      conversion to DHETs, which do not appear to be essential under routine
      conditions. Therefore, sEH is considered a potential therapeutic target for
      enhancing the beneficial functions of EETs.

PMID- 16988000
TI  - Parathyroid-specific double knockout of Gq and G11 alpha-subunits leads to a
      phenotype resembling germline knockout of the extracellular Ca2+ -sensing
      receptor.
AB  - Germline knockout of the extracellular Ca2+ -sensing receptor (CaR) leads to a
      phenotype that includes severe hypercalcemia, hyperparathyroidism, relative
      hypocalciuria, skeletal abnormalities, retarded growth, and early postnatal
      death. To investigate the role of heterotrimeric G proteins in CaR signaling, we
      used cre/lox technology to delete the respective alpha-subunits of Gq and G11
      selectively in parathyroid cells. Mice that were PTH-Cre(+/-); Gnaq(flox/flox);
      Gna11(-/-) (PTH-Galphaq/Galpha11 -double knockouts) were viable, but showed all
      the features of germline knockout of the CaR except hypocalcuria. Our results
      demonstrate the critical role of both Gq and G11 in mediating inhibition of PTH
      secretion by extracellular Ca2+.

PMID- 16988001
TI  - Activin A decreases glucagon and arx gene expression in alpha-cell lines.
AB  - Activin A is a potent growth and differentiation factor involved in development,
      differentiation, and physiological functions of the endocrine pancreas; it
      increases insulin and pax4 gene expression in beta-cells and can induce
      transdifferentiation of the exocrine acinar cell line AR42J into insulin
      producing cells. We show here that Activin A decreases glucagon gene expression
      in the alpha-cell lines InR1G9 and alphaTC1 in a dose- and time-dependent manner
      and that the effect is blocked by Follistatin. This effect is also observed in
      adult human islets. Glucagon gene expression is inhibited at the transcriptional
      level by the Smad signaling pathway through the G3 DNA control element.
      Furthermore, Activin A decreases cell proliferation of InR1G9 and alphaTC1 cells
      as well as cyclin D2 and arx gene expression, whose protein product Arx has been
      shown to be critical for alpha-cell differentiation. Overexpression of Arx in
      Activin A-treated InR1G9 cells does not prevent the decrease in glucagon gene
      expression but corrects the inhibition of cell proliferation, indicating that Arx
      mediates the Activin A effects on the cell cycle. We conclude that Activin A has
      opposite effects on alpha-cells compared with beta-cells, a finding that may have
      relevance during pancreatic endocrine lineage specification and physiological
      function of the adult islets.

PMID- 16988002
TI  - An in vitro model of human placental trophoblast deportation/shedding.
AB  - Deportation of trophoblast shed from the placenta into the maternal circulation
      was first described over 100 years ago. Despite this, little is known about the
      quantity or nature of the shed and deported trophoblasts. Neither do we have a
      clear understanding of the fate of deported trophoblasts nor do we have a clear
      understanding of their effects on the maternal physiology. This deficiency is
      largely due to the inaccessibility of deported trophoblasts in vivo. This study
      aimed to produce a model that would allow us to study deported trophoblasts. We
      devised a system for culturing placental explants of 12-week gestation in cell
      culture inserts with a stainless steel mesh bottom that allowed the ready
      harvesting of shed/deported trophoblasts. Immunohistochemical and morphologic
      investigations demonstrated that these in vitro shed/deported trophoblasts are
      similar to those found in vivo and that apoptotic, necrotic and viable
      trophoblasts were shed from the explants. Inhibiting caspases induced a change
      from predominantly apoptotic to predominantly necrotic trophoblast shedding. We
      have devised an in vitro model that allows the collection of shed/deported
      trophoblasts which will significantly enhance our ability to study these cells.
      Our preliminary investigations confirm that apoptosis plays an important role in
      trophoblast shedding/deportation.

PMID- 16988004
TI  - Compartmentalization of interleukin-6 response in a patient with septic
      meningococcal peritonitis.
AB  - We report the first case of Neisseria meningitidis-induced septic peritonitis
      diagnosed by PCR assay of peritoneal fluid. Concentrations of interleukin-6 were
      notably higher in the peritoneal fluid than in the blood. PCR diagnosis of septic
      meningococcal peritonitis and the pathogenesis of the disease are discussed.

PMID- 16988003
TI  - Evaluation of an enzyme immunoassay for detection of dengue virus NS1 antigen in
      human serum.
AB  - We evaluated a one-step sandwich-format microplate enzyme immunoassay for
      detecting dengue virus NS1 antigen (Ag) in human serum by use of Platelia Dengue
      NS1 Ag kits (Bio-Rad Laboratories, Marnes La Coquette, France). We collected 299
      serum samples from patients with dengue disease and 50 serum samples from
      patients not infected with dengue virus. For the 239 serum samples from patients
      with acute infections testing positive by reverse transcription-PCR and/or virus
      isolation for one of the four dengue virus serotypes, the sensitivity of the
      Platelia Dengue NS1 Ag kit was 88.7% (95% confidence interval, 84.0% to 92.4%).
      None of the serum samples from patients not infected with dengue virus tested
      positive with the Platelia Dengue NS1 Ag kit. A diagnostic strategy combining the
      Platelia Dengue NS1 Ag test for acute-phase sera and immunoglobulin M capture
      enzyme-linked immunosorbent assay for early-convalescent-phase sera increased
      sensitivity only from 88.7% to 91.9%. Thus, NS1 antigen detection with the
      Platelia Dengue NS1 Ag kit could be used for first-line testing for acute dengue
      virus infection in clinical diagnostic laboratories.

PMID- 16988005
TI  - Macaque multimeric soluble CD40 ligand and GITR ligand constructs are
      immunostimulatory molecules in vitro.
AB  - CD40 ligand (CD40L) and GITR ligand (glucocorticoid-induced tumor necrosis factor
      receptor-related protein ligand [GITRL]) are tumor necrosis factor superfamily
      molecules that can be used as vaccine adjuvants. In a previous human
      immunodeficiency virus (HIV) DNA vaccine study in mice, we found that plasmids
      expressing multimeric soluble forms of trimeric CD40L (i.e., many trimers) were
      stronger activators of CD8(+) T-cell responses than were single-trimer soluble
      forms or the natural membrane-bound molecule. This report describes similar
      multimeric soluble molecules that were constructed for studies in macaques. Both
      two-trimer and four-trimer forms of macaque CD40L were active in B-cell
      proliferation assays using macaque and human cells. With human cells, four-trimer
      macaque GITRL costimulated CD4(+) T-cell proliferation and abrogated the
      immunosuppressive effects of CD4(+) CD25(+) regulatory T cells on a mixed
      leukocyte reaction. These molecular adjuvants provide new tools for vaccine
      development in the simian immunodeficiency virus system and other macaque models.

PMID- 16988006
TI  - Effect of oral administration of Butyrivibrio fibrisolvens MDT-1 on experimental
      enterocolitis in mice.
AB  - Butyrivibrio fibrisolvens MDT-1, a butyrate-producing strain, was evaluated for
      use as a probiotic to prevent enterocolitis. Oral administration of the MDT-1
      strain (10(9) CFU/dose) alleviated the symptoms of colitis (including body weight
      loss, diarrhea, bloody stool, organic disorder, and mucosal damage) that are
      induced in mice drinking water that contains 3.0% dextran sulfate sodium. In
      addition, myeloperoxidase (MPO) activity levels in colonic tissue were reduced,
      suggesting that MDT-1 mitigates bowel inflammation. The addition of MDT-1 culture
      supernatant inhibited the growth of nine clinical isolates of Campylobacter
      jejuni and Campylobacter coli that could potentially cause enterocolitis.
      Infection of mice with C. coli 11580-3, one of the isolates inhibited by MDT-1 in
      vitro, resulted in diarrhea, mucosal damage, increased MPO activity levels in
      colonic tissue, increased numbers of C. coli in the cecum, and decreased body
      weight gain. However, administration of MDT-1 to mice, prior to and during C.
      coli infection, reduced these effects. These results suggest that Campylobacter
      induced enterocolitis can be alleviated by using B. fibrisolvens as a probiotic.

PMID- 16988007
TI  - Association of selective HLA class II susceptibility-conferring and protective
      haplotypes with type 2 diabetes in patients from Bahrain and Lebanon.
AB  - The association of HLA class II with type 2 diabetes (T2DM) was investigated in
      Bahraini and Lebanese subjects. DRB1*070101 (Lebanese and Bahraini) and DQB1*0201
      (Lebanese) were susceptibility-conferring alleles, and unique susceptibility
      conferring/protective haplotypes were found in both patient groups. Regression
      analysis confirmed that DRB1*070101-DQB1*0201 (Bahraini) and DRB1*110101
      DQB1*0201 (Lebanese) were susceptibility-conferring haplotypes.

PMID- 16988008
TI  - A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical
      trial.
AB  - Ebola viruses represent a class of filoviruses that causes severe hemorrhagic
      fever with high mortality. Recognized first in 1976 in the Democratic Republic of
      Congo, outbreaks continue to occur in equatorial Africa. A safe and effective
      Ebola virus vaccine is needed because of its continued emergence and its
      potential for use for biodefense. We report the safety and immunogenicity of an
      Ebola virus vaccine in its first phase I human study. A three-plasmid DNA vaccine
      encoding the envelope glycoproteins (GP) from the Zaire and Sudan/Gulu species as
      well as the nucleoprotein was evaluated in a randomized, placebo-controlled,
      double-blinded, dose escalation study. Healthy adults, ages 18 to 44 years, were
      randomized to receive three injections of vaccine at 2 mg (n = 5), 4 mg (n = 8),
      or 8 mg (n = 8) or placebo (n = 6). Immunogenicity was assessed by enzyme-linked
      immunosorbent assay (ELISA), immunoprecipitation-Western blotting, intracellular
      cytokine staining (ICS), and enzyme-linked immunospot assay. The vaccine was well
      tolerated, with no significant adverse events or coagulation abnormalities.
      Specific antibody responses to at least one of the three antigens encoded by the
      vaccine as assessed by ELISA and CD4(+) T-cell GP-specific responses as assessed
      by ICS were detected in 20/20 vaccinees. CD8(+) T-cell GP-specific responses were
      detected by ICS assay in 6/20 vaccinees. This Ebola virus DNA vaccine was safe
      and immunogenic in humans. Further assessment of the DNA platform alone and in
      combination with replication-defective adenoviral vector vaccines, in concert
      with challenge and immune data from nonhuman primates, will facilitate evaluation
      and potential licensure of an Ebola virus vaccine under the Animal Rule.

PMID- 16988009
TI  - Human immunodeficiency virus persistence and production in T-cell development.
AB  - Human immunodeficiency virus type 1 (HIV-1) replication depends on CD4 and
      coreceptor expression as well as host factors associated with the activation
      state of the cell. To determine the impact of the activation stage of thymocytes
      on the HIV-1 life cycle, we investigated R5 and X4 HIV-1 entry, reverse
      transcription, and expression in discrete thymocyte subsets at different stages
      of T-cell development. Early after infection, preferential entry and replication
      of R5 HIV-1 were predominantly detected in mature CD3(+/hi) CD27(+) thymocytes.
      Thus, R5 HIV-1 targets the stage of development where thymocytes acquire
      functional responsiveness, which has important implications for HIV pathogenesis.
      In contrast, X4 HIV-1 expression and replication were primarily found in immature
      CD3(-/+/low) CD27(-) CD69(-) thymocytes. HIV-1 proviral burden and virus
      expression in thymocyte subsets correlated with the expression of the highest
      levels of the respective coreceptor. R5 and X4 HIV-1 entered and completed
      reverse transcription in all subsets tested, indicating that the activation state
      of thymocytes and coreceptor expression are sufficient to support full reverse
      transcription throughout development. Although R5 HIV-1 is expressed mainly in
      mature CD3(+/hi) CD27(+) thymocytes, 5.3% of HIV-1-infected immature thymocytes
      express R5 HIV-1, indicating that potentially latent viral DNA can be established
      early in T-cell development.

PMID- 16988010
TI  - Deactivation of phosphatidylinositol 3,4,5-trisphosphate/Akt signaling mediates
      neutrophil spontaneous death.
AB  - Neutrophil spontaneous death plays essential roles in neutrophil homeostasis and
      resolution of inflammation, whereas the underlying molecular mechanisms are still
      ill-defined. Neutrophils die because of programmed cell death or apoptosis.
      However, treatment with inhibitor of caspases, which are responsible for the
      majority of apoptotic cell deaths, does not prevent the spontaneous death of
      neutrophils. PKB/Akt possesses prosurvival and antiapoptotic activities in a
      variety of cells. In this study, we show that Akt activity decreases dramatically
      during the course of neutrophil death. Both phosphatidylinositol 3-kinase and Akt
      inhibitors enhance neutrophil death. Conditions delaying neutrophil death, such
      as treatment with granulocyte-macrophage colony-stimulating factor, granulocyte
      colony-stimulating factor, or IFN-gamma, restore Akt activity. Finally, we
      demonstrate that neutrophils depleted of PTEN, a phosphatidylinositol 3'
      phosphatase that negatively regulates Akt activity, live much longer than WT
      neutrophils. Thus, we establish Akt deactivation as a causal mediator of
      neutrophil spontaneous death.

PMID- 16988011
TI  - Stimulation of AMP-activated protein kinase is essential for the induction of
      drug metabolizing enzymes by phenobarbital in human and mouse liver.
AB  - Our previous studies have suggested a role for AMP-activated protein kinase
      (AMPK) in the induction of CYP2B6 by phenobarbital (PB) in hepatoma-derived cells
      (Rencurel et al., 2005). In this study, we showed in primary human hepatocytes
      that: 1) 5'-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-beta-d-ribofuranoside
      and the biguanide metformin, known activators of AMPK, dose-dependently increase
      the expression of CYP2B6 and CYP3A4 to an extent similar to that of PB. 2) PB,
      but not the human nuclear receptor constitutive active/androstane receptor (CAR)
      ligand 6-(4-chlorophenyl)imidazol[2,1-6][1,3]thiazole-5-carbaldehyde, dose
      dependently increase AMPK activity. 3) Pharmacological inhibition of AMPK
      activity with compound C or dominant-negative forms of AMPK blunt the inductive
      response to phenobarbital. Furthermore, in transgenic mice with a liver-specific
      deletion of both the alpha1 and alpha2 AMPK catalytic subunits, basal levels of
      Cyp2b10 and Cyp3a11 mRNA were increased but not in primary culture of mouse
      hepatocytes. However, phenobarbital or 1,4 bis[2-(3,5
      dichloropyridyloxy)]benzene, a mouse CAR ligand, failed to induce the expression
      of these genes in the liver or cultured hepatocytes from mice lacking hepatic
      expression of the alpha1 and alpha2 subunits of AMPK. The distribution of CAR
      between the nucleus and cytosol was not altered in hepatocytes from mice lacking
      both AMPK catalytic subunits. These data highlight the essential role of AMPK in
      the CAR-mediated signal transduction pathway.

PMID- 16988012
TI  - Endogenous hepatic expression of the hepatitis B virus X-associated protein 2 is
      adequate for maximal association with aryl hydrocarbon receptor-90-kDa heat shock
      protein complexes.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor
      that acts as an environmental sensor by binding to a variety of xenobiotics. AHR
      activation serves to combat xenotoxic stress by inducing metabolic enzyme
      expression in the liver. The hepatitis B virus X-associated protein (XAP2) is a
      component of the cytosolic AHR complex and modulates AHR transcriptional
      properties in vitro and in cell culture and yeast systems. Expression of XAP2 is
      low in liver compared with other nonhepatic tissues and the AHR exhibits high
      ligand-induced transcriptional activity. Because XAP2 has been demonstrated to
      repress AHR activity, we hypothesized that XAP2 may be limiting in liver and that
      increasing XAP2 levels would attenuate AHR transcriptional activity. To this end,
      transgenic mice were generated that exhibit hepatocyte-specific elevation in XAP2
      expression. Transgenic XAP2 expression was restricted to liver, and its ability
      to complex with the AHR was verified. Gene expression experiments were performed
      by inducing AHR transcriptional activity with beta-naphthoflavone via
      intraperitoneal injection, and mRNA quantification was done by real-time
      polymerase chain reaction. Wild-type and transgenic animals showed little
      difference in constitutive or ligand-induced CYP1A1; CYP1A2; UDP
      glucuronosyltransferase 1A2; NAD(P)H dehydrogenase, quinone 1; constitutive
      androstane receptor; or nuclear factor erythroid 2-related factor 2 mRNA
      expression. Sucrose density fractionation and AHR immunoprecipitation experiments
      found little or no stoichiometric increase in bound XAP2 to the AHR between
      genotypes. Gene array studies were performed to identify novel XAP2-regulated
      targets. Taken together, this work shows that despite the relatively low level of
      XAP2 in liver, it is not a limiting component in AHR regulation.

PMID- 16988013
TI  - Analysis of the dissociated steroid RU24858 does not exclude a role for inducible
      genes in the anti-inflammatory actions of glucocorticoids.
AB  - Although repression of inflammatory gene expression makes glucocorticoids
      powerful anti-inflammatory agents, side effects limit usage and drive the search
      for improved glucocorticoid receptor (GR) ligands. In A549 pulmonary cells,
      dexamethasone and the prototypical dissociated ligand RU24858 (Mol Endocrinol
      11:1245-1255, 1997) repress interleukin (IL)-1beta-induced expression of
      cyclooxygenase (COX)-2 and IL-8. Although RU24858 is a weaker GR ligand, both
      glucocorticoids showed similar efficacies on transrepression of nuclear factor
      kappaB (NF-kappaB)-dependent transcription, whereas RU24858 yielded less than 12%
      of the response to dexamethasone on a classic glucocorticoid response element
      (GRE) reporter (transactivation). Modest NF-kappaB-dependent transrepression (
      approximately 40%), along with analysis of IL-8 transcription rate and the
      accumulation of unspliced nuclear RNA, indicates that transrepression does not
      fully account for the repression of genes such as IL-8. This was confirmed by the
      finding that mRNA degradation is increased by both dexamethasone and RU24858.
      Analysis of IL-1beta-induced steady-state mRNA levels for IL-8 and COX-2 show
      that dexamethasone- and RU24858-dependent repression of these genes is attenuated
      by inhibitors of transcription and protein synthesis. Because similar effects
      were observed with respect to COX-2 and IL-8 protein expression, we conclude that
      glucocorticoid-dependent gene expression is necessary for repression by both
      glucocorticoids. Despite RU24858 being defective at classic GRE-dependent
      transactivation, both dexamethasone and RU24858 induced the expression of
      potentially anti-inflammatory genes and metabolic genes, suggesting the
      importance of nontraditional glucocorticoid-dependent gene expression. Thus,
      classic transactivation- and transrepressionbased screens for anti-inflammatory
      "dissociated" GR ligands may be flawed because they may not reflect the effects
      on real glucocorticoid-inducible genes.

PMID- 16988014
TI  - Detection of rare G3P[19] porcine rotavirus strains in Chiang Mai, Thailand,
      provides evidence for origin of the VP4 genes of Mc323 and Mc345 human
      rotaviruses.
AB  - Among 175 fecal specimens collected from diarrheic piglets during a surveillance
      of porcine rotavirus (PoRV) strains in Chiang Mai, Thailand, 39 (22.3%) were
      positive for group A rotaviruses. Of these, 33.3% (13 of 39) belonged to G3P[19],
      which was a rare P genotype seldom reported. Interestingly, their VP4 nucleotide
      sequences were most closely related to human P[19] strains (Mc323 and Mc345)
      isolated in 1989 from the same geographical area where these PoRV strains were
      isolated. These P[19] PoRV strains were also closely related to another human
      P[19] strain (RMC321), isolated from India in 1990. The VP4 sequence identities
      with human P[19] were 95.4% to 97.4%, while those to a porcine P[19] strain (4F)
      were only 87.6 to 89.1%. Phylogenetic analysis of the VP4 gene revealed that PoRV
      P[19] strains clustered with human P[19] strains in a monophyletic branch
      separated from strain 4F. Analysis of the VP7 gene confirmed that these strains
      belonged to the G3 genotype and shared 97.7% to 98.3% nucleotide identities with
      other G3 PoRV strains circulating in the regions. This close genetic relationship
      was also reflected in the phylogenetic analysis of their VP7 genes. Altogether,
      the findings provided peculiar evidence that supported the porcine origin of VP4
      genes of Mc323 and Mc345 human rotaviruses.

PMID- 16988015
TI  - Molecular analysis of clinical isolates of Mycobacterium bovis recovered from
      humans in Italy.
AB  - In order to achieve a better knowledge of Mycobacterium bovis epidemiology in
      Italy, 42 clinical isolates from humans were genotyped. Predominant molecular
      patterns were found in one cluster of 15 isolates sharing spoligotype (ST482),
      variable-number tandem repeat (VNTR), and IS6110-based restriction fragment
      length polymorphism (one 1.9-kb band) profiles and in two clusters of 6 and 3
      Mycobacterium bovis BCG isolates differing by one VNTR character. The remaining
      18 isolates yielded unique profiles. Our results confirm the potential utility of
      spoligotyping and VNTR typing as a major typing system of M. bovis isolates.

PMID- 16988016
TI  - Differences between tissue-associated intestinal microfloras of patients with
      Crohn's disease and ulcerative colitis.
AB  - A leading hypothesis for the role of bacteria in inflammatory bowel diseases is
      that an imbalance in normal gut flora is a prerequisite for inflammation. Testing
      this hypothesis requires comparisons between the microbiota compositions of
      ulcerative colitis and Crohn's disease patients and those of healthy individuals.
      In this study, we obtained biopsy samples from patients with Crohn's disease and
      ulcerative colitis and from healthy controls. Bacterial DNA was extracted from
      the tissue samples, amplified using universal bacterial 16S rRNA gene primers,
      and cloned into a plasmid vector. Insert-containing colonies were picked for high
      throughput sequencing, and sequence data were analyzed, yielding species-level
      phylogenetic data. The clone libraries yielded 3,305 sequenced clones,
      representing 151 operational taxonomical units. There was no significant
      difference between floras from inflamed and healthy tissues from within the same
      individual. Proteobacteria were significantly (P = 0.0007) increased in Crohn's
      disease patients, as were Bacteroidetes (P < 0.0001), while Clostridia were
      decreased in that group (P < 0.0001) in comparison with the healthy and
      ulcerative colitis groups, which displayed no significant differences. Thus, the
      bacterial flora composition of Crohn's patients appears to be significantly
      altered from that of healthy controls, unlike that of ulcerative colitis
      patients. Imbalance in flora in Crohn's disease is probably not sufficient to
      cause inflammation, since microbiotas from inflamed and noninflamed tissues were
      of similar compositions within the same individual.

PMID- 16988017
TI  - CTX-M-3 and CTX-M-15 extended-spectrum beta-lactamases in isolates of Escherichia
      coli from a hospital in Algiers, Algeria.
AB  - Sixteen strains of Escherichia coli isolated between January and June 2005 in a
      hospital in Algiers carry the ISEcp1 element and the TEM and either CTX-M-3 (n=3)
      or CTX-M-15 (n=13) beta-lactamases. Fourteen of the isolates are multidrug
      resistant. Five isolates from the neonatal ward were indistinguishable by pulsed
      field gel electrophoresis.

PMID- 16988018
TI  - Culture-independent analyses of temporal variation of the dominant fecal
      microbiota and targeted bacterial subgroups in Crohn's disease.
AB  - Gut microbiota shows host-specific diversity and temporal stability and
      significantly contributes to maintenance of a healthy gut. However, in
      inflammatory bowel disease, this microbiota has been implicated as a contributory
      factor to the illness. This study compared bacterial dynamics in Crohn's disease
      patients to those in a control group using a culture-independent method to assess
      the temporal stability, relative diversity, and similarity of the dominant fecal
      microbiota, Clostridium spp., Bacteroides spp., Bifidobacterium spp., and lactic
      acid bacteria spp. (LAB) for all individuals. Fecal samples were collected over
      several time points from individuals with Crohn's disease who were in remission
      (n = 11), from Crohn's disease patients who relapsed into an active Crohn's
      disease state (n = 5), and from a control group (n = 18). Denaturing gradient gel
      electrophoresis profiles were generated for the different microbial groups by
      specifically targeting different regions of the 16S rRNA gene and were compared
      on the basis of similarity and diversity. The temporal stability of dominant
      species for all Crohn's disease patients was significantly lower (P < 0.005) than
      that for the control group. Analysis of group-specific profiles for
      Bifidobacterium spp. found that they were similar in all samples, while the
      diversity of the LAB varied significantly between the groups, but temporal
      stability was not significantly altered. We observed significant changes in two
      functionally important mutualistic groups of bacteria, viz., Clostridium and
      Bacteroides spp., which may have implications for the host's gut health, since
      some genera are involved in production of short-chain fatty acid, e.g., butyrate.

PMID- 16988019
TI  - Multiplex real-time reverse transcription-PCR assay for determination of
      hepatitis C virus genotypes.
AB  - A variety of methods have been used to determine hepatitis C virus (HCV)
      genotypes. Because therapeutic decisions for chronic HCV-related hepatitis are
      made on the basis of genotype, it is important that genotype be accurately
      determined by clinical laboratories. Existing methods are often subjective,
      inaccurate, manual, time-consuming, and contamination prone. We therefore
      evaluated real-time reverse transcription-PCR (RT-PCR) reagents that have
      recently become commercially available (Abbott HCV Genotype ASR). The assay
      developed by our laboratory starts with purified RNA and can be performed in 4 to
      5 h. An initial evaluation of 479 samples was done with a restriction fragment
      length polymorphism (RFLP) method and the RT-PCR assay, and discrepant samples
      were sequenced. An additional 1,200 samples were then tested, and data from all
      assays were used to evaluate the efficiency and specificity of each genotype
      specific reaction. Good correlation between results by the two methods was seen.
      Discrepant samples included those indeterminate by the RT-PCR assay (n = 110) and
      a subset that were incorrectly called 2a by the RFLP method (n = 75). The real
      time RT-PCR assay performed well with genotype 1, 2, and 3 samples. Inadequate
      numbers of samples were available to evaluate fully genotypes 4, 5, and 6.
      Analysis of each primer-probe set demonstrated that weak cross-reactive
      amplifications were common but usually did not interfere with the genotype
      determination. However, in about 1% of samples, two or more genotypes amplified
      at roughly equivalent amounts. Further studies are necessary to determine whether
      these mixed-genotype samples are true mixtures or a reflection of occasional
      cross-reactive amplifications.

PMID- 16988020
TI  - Production of monoclonal antibodies to Tropheryma whipplei and identification of
      recognized epitopes by two-dimensional electrophoresis and mass spectrometry.
AB  - Tropheryma whipplei, the agent of Whipple's disease, is a gram-positive rod
      shaped bacterium that belongs to the group of actinobacteria. In order to produce
      monoclonal antibodies (MAbs) against this bacterium, we inoculated mice with two
      different strains, Slow2 and Endo5. We produced 13 and 10 MAbs against Slow2 and
      Endo5, respectively. Nine of the Slow2 MAbs and seven of the Endo5 MAbs
      recognized a 58-kDa epitope. In addition, three other Endo5 MAbs detected a
      unique 84-kDa epitope. These MAbs were species specific, as they did not react
      with a selection of 22 different bacterial species, but they were not strain
      specific, as they did react with six other strains of T. whipplei. Two
      dimensional gel electrophoresis (2-DE) was combined with mass spectrometry (MS)
      to identify the 58-kDa and 84-kDa epitopes recognized by MAbs. After trypsin in
      gel digestion of the spot, the 58-kDa protein was identified as an ATP synthase
      F1 complex beta chain, whereas the 84-kDa protein was identified as a
      polyribonucleotide nucleotidyltransferase by MS with matrix-assisted laser
      desorption ionization-time of flight. In an in vitro model, one of these MAbs
      allowed good detection of T. whipplei in stool samples, contrary to a rabbit
      polyclonal antibody, which led to high fluorescent background. In the prospective
      studies, the produced MAb will be tested for detection of T. whipplei in clinical
      samples, and the gene coding for identified 58-kDa and 84-kDa antigens will be
      tentatively cloned and then tested for its use in a diagnostic enzyme-linked
      immunosorbent assay for Whipple's disease.

PMID- 16988021
TI  - Presence of copper- and zinc-containing superoxide dismutase in commensal
      Haemophilus haemolyticus isolates can be used as a marker to discriminate them
      from nontypeable H. influenzae isolates.
AB  - Respiratory isolates of Haemophilus haemolyticus are regularly misclassified as
      nontypeable (NT) Haemophilus influenzae due to an aberrant hemolytic reaction on
      blood agar, with implications for treatment. The presence of sodC or its cognate
      protein, copper-zinc superoxide dismutase, can distinguish respiratory isolates
      of H. haemolyticus from NT H. influenzae with 100% accuracy.

PMID- 16988022
TI  - Fatal granulomatous Acanthamoeba encephalitis mimicking a stroke, diagnosed by
      correlation of results of sequential magnetic resonance imaging, biopsy, in vitro
      culture, immunofluorescence analysis, and molecular analysis.
AB  - Amebic infections involving the central nervous system are rare and difficult to
      diagnose. Magnetic resonance imaging (MRI) at timed intervals may be helpful,
      where scans reveal enhancing lesions and increased signal. We report a unique
      case of granulomatous amebic encephalitis that was proven pathologically with
      progressive radiological findings on MRI.

PMID- 16988023
TI  - Usefulness of inter-IS1 spacer polymorphisms for subtyping of Shigella sonnei
      isolates.
AB  - Shigella sonnei contains numerous IS1 elements. The existence of polymorphisms in
      the length of the inter-IS1 spacer is a basis for the development of a PCR-based
      method for the subtyping of S. sonnei strains. The usefulness of inter-IS1 spacer
      typing (IST) was evaluated and compared with that of pulsed-field gel
      electrophoresis (PFGE) by characterization of S. sonnei isolates from
      epidemiologically nonrelated cases and outbreaks and of isolates that were
      indistinguishable by PFGE and that were collected from independent infection
      events. IST was less discriminatory than PFGE, with discriminatory indices of
      0.96 and 0.63, respectively, but was able to compensate for the drawbacks of
      PFGE. PFGE exhibited a high level of discriminatory power for S. sonnei isolates;
      however, PFGE was also, at times, too discriminatory, which was a disadvantage in
      constructing the clonal relationships among strains circulating over a period of
      months or years. Furthermore, IST provided greater subtyping information for
      isolates indistinguishable by PFGE. The present study indicates that IST is more
      useful than PFGE for investigating the genetic relationships among S. sonnei
      strains circulating over a longer time span and also for discriminating certain
      strains which are indistinguishable by PFGE.

PMID- 16988024
TI  - Integrin ligands at a glance.

PMID- 16988025
TI  - Lucky 13-microtubule depolymerisation by kinesin-13 motors.
AB  - The kinesin-13 class of motors catalyses microtubule depolymerisation by bending
      tubulins at microtubule ends. Depolymerisation activity is intrinsic to the
      kinesin-13 motor core but the activity of the core alone is very low compared
      with that of constructs that also contain a conserved neck sequence. The full
      length dimeric motor is an efficient depolymeriser and also diffuses along the
      microtubule lattice, which helps it to find microtubule ends. Current evidence
      supports the idea of a generic mechanism for kinesin-13-catalysed
      depolymerisation. However, the activity of kinesin-13 motors is precisely
      localised and regulated in vivo to enable a wide range of cellular roles. The
      proteins are involved in global control of microtubule dynamics. They also
      localise to mitotic and meiotic spindles, where they contribute to formation and
      maintenance of spindle bipolarity, chromosomal congression, attachment correction
      and chromatid separation. In interphase cells, intricate and subtle mechanisms
      appear to allow kinesin-13 motors to act on specific populations of microtubules.
      Such carefully controlled localisation and regulation makes these kinesins
      efficient, multi-tasking molecular motors.

PMID- 16988026
TI  - Calcium signalling during excitation-contraction coupling in mammalian atrial
      myocytes.
AB  - Atrial cardiomyocytes make an important contribution to the refilling of
      ventricles with blood, which enhances the subsequent ejection of blood from the
      heart. The dependence of cardiac function on the contribution of atria becomes
      increasingly important with age and exercise. We know much less about the calcium
      signals that link electrical depolarisation to contraction within atrial myocytes
      in comparison with ventricular myocytes. Nevertheless, recent work has shed new
      light on calcium signalling in atrial cells. At an ultrastructural level, atrial
      and ventricular myocytes have many similarities. However, a few key structural
      differences, in particular the lack of transverse tubules (;T-tubules') in atrial
      myocytes, make these two cell types display vastly different calcium patterns in
      response to depolarisation. The lack of T-tubules in atrial myocytes means that
      depolarisation provokes calcium signals that largely originate around the
      periphery of the cells. To engage the contractile machinery, the calcium signal
      must propagate centripetally deeper into the cells. This inward movement of
      calcium is ultimately controlled by hormones that can promote or decrease calcium
      release within the myocytes. Enhanced centripetal movement of calcium in atrial
      myocytes leads to increased contraction and a more substantial contribution to
      blood pumping. The calcium signalling paradigm within atrial cells applies to
      other cardiac cell types that also do not express T-tubules, such as neonatal
      ventricular myocytes, and Purkinje cells that aid in the spread of electrical
      depolarisation. Furthermore, during heart failure ventricular myocytes
      progressively lose their regular T-tubule expression, and their pattern of
      response resembles that of atrial cells.

PMID- 16988027
TI  - Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation
      and delays nerve regeneration after damage.
AB  - Axonal loss causes disabling and permanent deficits in many peripheral
      neuropathies, and may result from inefficient nerve regeneration due to a
      defective relationship between Schwann cells, axons and the extracellular matrix.
      These interactions are mediated by surface receptors and transduced by
      cytoskeletal molecules. We investigated whether peripheral nerve regeneration is
      perturbed in mice that lack glial fibrillary acidic protein (GFAP), a Schwann
      cell-specific cytoskeleton constituent upregulated after damage. Peripheral
      nerves develop and function normally in GFAP-null mice. However, axonal
      regeneration after damage was delayed. Mutant Schwann cells maintained the
      ability to dedifferentiate but showed defective proliferation, a key event for
      successful nerve regeneration. We also showed that GFAP and the other Schwann
      cell-intermediate filament vimentin physically interact in two distinct signaling
      pathways involved in proliferation and nerve regeneration. GFAP binds integrin
      alphavbeta8, which initiates mitotic signals soon after damage by interacting
      with fibrin. Consistently, ERK phosphorylation was reduced in crushed GFAP-null
      nerves. Vimentin instead binds integrin alpha5beta1, which regulates
      proliferation and differentiation later in regeneration, and may compensate for
      the absence of GFAP in mutant mice. GFAP might contribute to form macro-complexes
      to initiate mitogenic and differentiating signaling for efficient nerve
      regeneration.

PMID- 16988028
TI  - Triptan migraine treatments and antidepressants: risk of serotonin syndrome.

PMID- 16988030
TI  - As we may read.

PMID- 16988031
TI  - Kv2.1 potassium channels are retained within dynamic cell surface microdomains
      that are defined by a perimeter fence.
AB  - Ion channel localization to specific cell surface regions is essential for proper
      neuronal function. The Kv2.1 K+ channel forms large clusters on the plasma
      membrane of hippocampal neurons and transfected human embryonic kidney (HEK)
      cells. Using live cell imaging, we address mechanisms underlying this Kv2.1
      clustering in both HEK cells and cultured hippocampal neurons. The Kv2.1
      containing surface clusters have properties unlike those expected for a
      scaffolding protein bound channel. After channel is delivered to the plasma
      membrane via intracellular transport vesicles, it remains localized at the
      insertion site. Fluorescence recovery after photobleaching (FRAP) and quantum dot
      tracking experiments indicate that channel within the surface cluster is mobile
      (FRAP, tau = 14.1 +/- 1.5 and 11.5 +/- 6.1 s in HEK cells and neurons,
      respectively). The cluster perimeter is not static, because after fusion of
      adjacent clusters, green fluorescent protein (GFP)-Kv2.1 completely exchanged
      between the two domains within 60 s. Treatment of hippocampal neurons expressing
      GFP-Kv2.1 with 5 microM latrunculin A resulted in a significant increase in
      average cluster size from 0.89 +/- 0.16 microm2 to 12.15 +/- 1.4 microm2 with a
      concomitant decrease in cluster number. Additionally, Kv2.1 was no longer
      restricted to the cell body, suggesting a role for cortical actin in both cluster
      maintenance and localization. Thus, Kv2.1 surface domains likely trap mobile
      Kv2.1 channels within a well defined, but fluid, perimeter rather than being
      tightly bound to a scaffolding protein-containing complex. Channel moves directly
      into these clusters via trafficking vesicles. Such domains allow for efficient
      trafficking to the cell surface while sequestering channel with signaling
      proteins.

PMID- 16988032
TI  - Real-time contributions of auditory feedback to avian vocal motor control.
AB  - Songbirds and humans both rely critically on hearing for learning and maintaining
      accurate vocalizations. Evidence strongly indicates that auditory feedback
      contributes in real time to human speech, but similar contributions of feedback
      to birdsong remain unclear. Here, we assessed real-time influences of auditory
      feedback on Bengalese finch song using a computerized system to detect targeted
      syllables as they were being sung and to disrupt feedback transiently at short
      and precisely controlled latencies. Altered feedback elicited changes within tens
      of milliseconds to both syllable sequencing and timing in ongoing song. These
      vocal disruptions were larger when feedback was altered at segments of song with
      variable sequence transitions than at stereotyped sequences. As in humans, these
      effects depended on the feedback delay relative to ongoing song, with the most
      disruptive delays approximating the average syllable duration. These results
      extend the parallels between speech and birdsong with respect to a moment-by
      moment reliance on auditory feedback. Moreover, they demonstrate that song
      premotor circuitry is sensitive to auditory feedback during singing and suggest
      that feedback may contribute in real time to the control and calibration of song.

PMID- 16988033
TI  - Acute changes in frontoparietal activity after repetitive transcranial magnetic
      stimulation over the dorsolateral prefrontal cortex in a cued reaction time task.
AB  - Lesion and functional imaging studies in humans have suggested that the
      dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC),
      and intraparietal sulcus (IPS) are involved in orienting attention. A functional
      magnetic resonance imaging study supplemented by a behavioral experiment examined
      the effects of 5 Hz repetitive transcranial magnetic stimulation (rTMS)
      conditioning to the right and left DLPFC on reaction times and synaptic activity
      as indexed by changes in the blood oxygenation level-dependent (BOLD) signal
      during a cued choice reaction time task. Orienting precues were either correct
      (valid) or incorrect (invalid) with respect to the subsequent move cue. The
      effects of real and sham rTMS were compared for each site of stimulation. Invalid
      trials showed a significant increase in response times and increases in the BOLD
      signal in right frontal and parietal regions when compared with valid trials.
      Conditioning left DLPFC with rTMS led to decreased BOLD signal during performance
      of this reorienting task in areas including left VLPFC and left IPS. Comparing
      invalid to valid trials after right DLPFC conditioning revealed decreased BOLD
      signal in right VLPFC. Data from the behavioral study showed that right DLPFC
      rTMS selectively increases response times in invalid trials. This effect was only
      present in the first 10 min after rTMS conditioning. No effect was found in
      either validly or invalidly cued trials with left DLPFC conditioning. These
      results suggest that 5 Hz rTMS over right DLPFC exerts remote effects on the
      activity of areas that functionally interact with the DLPFC during attentional
      processes, particularly when the reorienting of attention is more demanding as in
      invalid trials.

PMID- 16988034
TI  - Dissociation between local field potentials and spiking activity in macaque
      inferior temporal cortex reveals diagnosticity-based encoding of complex objects.
AB  - Neurons in the inferior temporal (IT) cortex respond selectively to complex
      objects, and maintain their selectivity despite partial occlusion. However,
      relatively little is known about how the occlusion of different shape parts
      influences responses in the IT cortex. Here, we determine experimentally which
      parts of complex objects monkeys are relying on in a discrimination task. We then
      study the effect of occlusion of parts with different behavioral relevance on
      neural responses in the IT cortex at the level of spiking activity and local
      field potentials (LFPs). For both spiking activity and LFPs, we found that the
      diagnostic object parts, which were important for behavioral judgments, were
      preferentially represented in the IT cortex. Our data show that the effects of
      diagnosticity grew systematically stronger along a posterior-anterior axis for
      LFPs, but were evenly distributed for single units, suggesting that diagnosticity
      is first encoded in the posterior IT cortex. Our findings highlight the power of
      combined analysis of field potentials and spiking activity for mapping structure
      to computational function in the brain.

PMID- 16988035
TI  - Schwann cells express motor and sensory phenotypes that regulate axon
      regeneration.
AB  - Schwann cell phenotype is classified as either myelinating or nonmyelinating.
      Additional phenotypic specialization is suggested, however, by the preferential
      reinnervation of muscle pathways by motoneurons. To explore potential differences
      in growth factor expression between sensory and motor nerve, grafts of cutaneous
      nerve or ventral root were denervated, reinnervated with cutaneous axons, or
      reinnervated with motor axons. Competitive reverse transcription-PCR was
      performed on normal cutaneous nerve and ventral root and on graft preparations 5,
      15, and 30 d after surgery. mRNA for nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF), vascular endothelial growth factor, hepatocyte growth
      factor, and insulin-like growth factor-1 was expressed vigorously by denervated
      and reinnervated cutaneous nerve but minimally by ventral root. In contrast, mRNA
      for pleiotrophin (PTN) and glial cell line-derived neurotrophic factor was
      upregulated to a greater degree in ventral root. ELISA confirmed that NGF and
      BDNF protein were significantly more abundant in denervated cutaneous nerve than
      in denervated ventral root, but that PTN protein was more abundant in denervated
      ventral root. The motor phenotype was not immutable and could be modified toward
      the sensory phenotype by prolonged reinnervation of ventral root by cutaneous
      axons. Retrograde labeling to quantify regenerating neurons demonstrated that
      cutaneous nerve preferentially supported cutaneous axon regeneration, whereas
      ventral root preferentially supported motor axon regeneration. Schwann cells thus
      express distinct sensory and motor phenotypes that are associated with the
      support of regeneration in a phenotype-specific manner. These findings suggest
      that current techniques of bridging gaps in motor and mixed nerve with cutaneous
      graft could be improved by matching axon and Schwann cell properties.

PMID- 16988036
TI  - Altered attention and prefrontal cortex gene expression in rats after binge-like
      exposure to cocaine during adolescence.
AB  - Illicit use of drugs frequently begins and escalates during adolescence, with
      long-term adverse consequences. Because it is increasingly accepted that neural
      development continues through adolescence, addiction research has become more
      invested in understanding the behavioral and molecular consequences of early
      exposure to drugs of abuse. In a novel binge administration paradigm designed to
      model the pattern of human adolescent drug use, we administered ascending doses
      of cocaine or saline during a 12-d developmental period [postnatal day 35 (P35)
      to P46] corresponding to human adolescence. During adulthood (P70), rats treated
      with this regimen displayed increased responsiveness to the stimulant effects of
      cocaine. Adult rats also displayed abnormally rapid shifts in attention when
      performing an attentional set-shifting task, which measures the ability to shift
      attention between stimuli and whose performance requires an intact prefrontal
      cortex (PFC). Treatment with cocaine during adolescence also caused acute
      alterations in the expression of genes encoding cell adhesion molecules and
      transcription factors within the PFC. Furthermore, we observed decreases in
      histone methylation, which may indicate a role for chromatin remodeling in the
      observed changes in gene expression patterns. These findings suggest that
      exposure to cocaine during adolescence has far-reaching molecular and behavioral
      consequences in the rat PFC that develop over time and endure long after drug
      administration has ceased.

PMID- 16988037
TI  - Vanilloid-mediated heterosynaptic facilitation of inhibitory synaptic input to
      neurons of the rat dorsal motor nucleus of the vagus.
AB  - Vanilloid type-1 receptors (VR1) are abundant in the dorsal vagal complex, where
      their function is mostly unknown. We examined the role of VR1 in regulating
      synaptic inputs to neurons of the dorsal motor nucleus of the vagus (DMV). Using
      patch-clamp recordings from DMV neurons in brainstem slices, capsaicin was found
      to increase action potential-independent inhibitory input onto DMV neurons. This
      rapid effect was mimicked by application of the endogenous cannabinoid,
      anandamide and blocked by VR1 antagonists. The VR1-mediated facilitation of
      synaptic inhibition was reduced by ionotropic and metabotropic glutamate receptor
      antagonists, suggesting an indirect, heterosynaptic enhancement of GABA release
      caused by a VR1-mediated increase in glutamate release from presynaptic terminals
      of excitatory neurons. Application of L-glutamate also increased GABA release.
      The paired-pulse ratio was increased for IPSCs evoked after electrical
      stimulation of the nucleus tractus solitarius, but the effect was slower than for
      the enhancement of spontaneous and miniature IPSCs. Capsaicin also increased the
      frequency of glutamatergic postsynaptic currents in a VR1-mediated manner.
      Results of these studies suggest that VR1-containing glutamatergic terminals
      contact DMV neurons. Activation of VR1 potently enhances glutamate release onto
      GABAergic terminals, facilitating GABA release. Endogenous cannabinoids can
      thereby rapidly enhance inhibitory input to DMV neurons via VR1-mediated
      presynaptic mechanisms.

PMID- 16988038
TI  - Triplets of spikes in a model of spike timing-dependent plasticity.
AB  - Classical experiments on spike timing-dependent plasticity (STDP) use a protocol
      based on pairs of presynaptic and postsynaptic spikes repeated at a given
      frequency to induce synaptic potentiation or depression. Therefore, standard STDP
      models have expressed the weight change as a function of pairs of presynaptic and
      postsynaptic spike. Unfortunately, those paired-based STDP models cannot account
      for the dependence on the repetition frequency of the pairs of spike. Moreover,
      those STDP models cannot reproduce recent triplet and quadruplet experiments.
      Here, we examine a triplet rule (i.e., a rule which considers sets of three
      spikes, i.e., two pre and one post or one pre and two post) and compare it to
      classical pair-based STDP learning rules. With such a triplet rule, it is
      possible to fit experimental data from visual cortical slices as well as from
      hippocampal cultures. Moreover, when assuming stochastic spike trains, the
      triplet learning rule can be mapped to a Bienenstock-Cooper-Munro learning rule.

PMID- 16988039
TI  - Modulation of transient and sustained response components of V4 neurons by
      temporal crowding in flashed stimulus sequences.
AB  - The responses of extrastriate area V4 neurons to flashed visual stimuli were
      examined to determine whether the responses to stimulus sequences occurring at
      normal saccade and fixation timing intervals were degraded relative to longer
      timing intervals. Stimuli were flashed in receptive fields in the near periphery
      while monkeys maintained steady fixation. Short interstimulus intervals (ISIs)
      resulted in an overall habituation style response reduction. The transient
      component of responses to preferred stimuli was suppressed, often completely,
      when the ISI was reduced below 100 ms into the range of saccadic durations. The
      sustained response component weakened but remained intact. At short ISIs the
      trailing activity from the preceding stimulus blended with onset activity from
      the next stimulus, making it difficult to detect individual stimulus onset events
      within the spike train. Habituation or conditioning effects were correlated with
      the stimulus tuning sensitivity of the neuron but only loosely associated with
      the actual level of V4 activation elicited by preceding stimuli. The results
      suggest that sharply tuned neurons, because of their probabilistic inactivity,
      are particularly sensitive to temporal change, whereas the sustained components
      of broadly tuned neurons could provide a continuity of information flow across
      visual transients, such as saccades, that do not alter significantly the view by
      the neuron of the scene.

PMID- 16988040
TI  - Area postrema neurons are modulated by the adipocyte hormone adiponectin.
AB  - Adiponectin is an adipocyte-derived peptide hormone involved in energy
      homeostasis and the pathogenesis of obesity, including hypertension. Area
      postrema (AP) lacks a blood-brain barrier and is a critical homeostatic
      integration center for humoral and neural signals. Here we investigate the role
      of AP in adiponectin signaling. We show that rat AP expresses AdipoR1 and AdipoR2
      adiponectin receptor mRNA. We used current-clamp electrophysiology to investigate
      whether adiponectin influenced membrane properties of AP neurons and found that
      approximately 60% of rat AP neurons tested were sensitive to adiponectin.
      Additional electrophysiology experiments coupled with single-cell reverse
      transcription-PCR indicated that all neurons that expressed both subtypes of
      receptor were sensitive to adiponectin, whereas neurons expressing only one
      subtype were predominantly insensitive. Last, microinjection of adiponectin into
      AP caused significant increases in arterial blood pressure, with no change in
      heart rate, suggesting that adiponectin acts at AP to provide a possible link
      between control of energy homeostasis and cardiovascular function.

PMID- 16988041
TI  - Tumor necrosis factor receptor 1 is a negative regulator of progenitor
      proliferation in adult hippocampal neurogenesis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine, acting
      through the TNF-R1 and TNF-R2 receptors. The two receptors have been proposed to
      mediate distinct TNF-alpha effects in the CNS, TNF-R1 contributing to neuronal
      damage and TNF-R2 being neuroprotective. Whether TNF-alpha and its receptors play
      any role for neurogenesis in the adult brain is unclear. Here we used mouse
      models with loss of TNF-R1 and TNF-R2 function to establish whether signaling
      through these receptors could influence hippocampal neurogenesis in vivo under
      basal conditions, as well as after status epilepticus (SE), which is associated
      with inflammation and elevated TNF-alpha levels. Notably, in the intact brain,
      the number of new, mature hippocampal neurons was elevated in TNF-R1(-/-) and TNF
      R1/R2(-/-) mice, whereas no significant changes were detected in TNF-R2(-/-)
      mice. Also after SE, the TNF-R1(-/-) and TNF-R1/R2(-/-) mice produced more new
      neurons. In contrast, the TNF-R2(-/-) mice showed reduced SE-induced
      neurogenesis. Cell proliferation in the dentate subgranular zone was elevated in
      TNF-R1(-/-) and TNF-R1/R2(-/-) mice both under basal conditions and after SE. The
      TNF-R2(-/-) mice either showed no change or minor decrease of cell proliferation.
      TNF-R1 and TNF-R2 receptors were expressed by hippocampal progenitors, as
      assessed with reverse transcription-PCR on sorted or cultured cells and
      immunocytochemistry on cultures. Our data reveal differential actions of TNF-R1
      and TNF-R2 signaling in adult hippocampal neurogenesis and identify for the first
      time TNF-R1 as a negative regulator of neural progenitor proliferation in both
      the intact and pathological brain.

PMID- 16988042
TI  - Neurotrophin-3 gradients established by lentiviral gene delivery promote short
      distance axonal bridging beyond cellular grafts in the injured spinal cord.
AB  - Neurotrophic factor delivery to sites of spinal cord injury (SCI) promotes axon
      growth into but not beyond lesion sites. We tested the hypothesis that sustained
      growth factor gradients beyond regions of SCI will promote significant axonal
      bridging into and beyond lesions. Adult rats underwent C3 lesions to transect
      ascending dorsal column sensory axons, and autologous bone marrow stromal cells
      were grafted into the lesion to provide a cellular bridge for growth into the
      injured region. Concurrently, lentiviral vectors expressing neurotrophin-3 (NT-3)
      or green fluorescent protein (GFP) (controls) were injected into the host cord
      rostral to the lesion to promote axon extension beyond the graft/lesion. Four
      weeks later, NT-3 gradients beyond the lesion were detectable by ELISA in animals
      that received NT-3-expressing lentiviral vectors, with highest average NT-3
      levels located near the rostral vector injection site. Significantly more
      ascending sensory axons extended into tissue rostral to the lesion site in
      animals injected with NT-3 vectors compared with GFP vectors, but only if the
      zone of NT-3 vector transduction extended continuously from the injection site to
      the graft; any "gap" in NT-3 expression from the graft to rostral tissue resulted
      in axon bridging failure. Despite axon bridging beyond the lesion, regenerating
      axons did not continue to grow over very long distances, even in the presence of
      a continuing growth factor gradient beyond the lesion. These findings indicate
      that a localized and continuous gradient of NT-3 can achieve axonal bridging
      beyond the glial scar, but growth for longer distances is not sustainable simply
      with a trophic stimulus.

PMID- 16988043
TI  - Identification of Sox17 as a transcription factor that regulates oligodendrocyte
      development.
AB  - Microarray analysis of oligodendrocyte lineage cells purified by fluorescence
      activated cell sorting (FACS) from 2',3'-cyclic nucleotide 3'-phosphodiesterase
      (CNP)-enhanced green fluorescent protein (EGFP) transgenic mice revealed Sox17
      (SRY-box containing gene 17) gene expression to be coordinately regulated with
      that of four myelin genes during postnatal development. In CNP-EGFP-positive (CNP
      EGFP+) cells, Sox17 mRNA and protein levels transiently increased between
      postnatal days 2 and 15, with white matter O4+ preoligodendrocytes expressing
      greater Sox17 levels than Nkx2.2+ (NK2 transcription factor related, locus 2)
      NG2+, or GalC+ (galactocerebroside) cells. In spinal cord, Sox17 protein
      expression was undetectable in the primary motor neuron domain between embryonic
      days 12.5 and 15.5 but was evident in Nkx2.2+ and CC1+ cells. In cultured
      oligodendrocyte progenitor cells (OPCs), Sox17 levels were maximal in O4+ cells
      and peaked during the phenotypic conversion from bipolar to multipolar. Parallel
      increases in Sox17 and p27 occurred before MBP protein expression, and Sox17
      upregulation was prevented by conditions inhibiting differentiation. Sox17
      downregulation with small interfering RNAs increased OPC proliferation and
      decreased lineage progression after mitogen withdrawal, whereas Sox17
      overexpression in the presence of mitogen had opposite effects. Sox17
      overexpression enhanced myelin gene expression in OPCs and directly stimulated
      MBP gene promoter activity. These findings support important roles for Sox17 in
      controlling both oligodendrocyte progenitor cell cycle exit and differentiation.

PMID- 16988044
TI  - A mirror representation of others' actions in the human anterior parietal cortex.
AB  - The anterior part of the human intraparietal sulcus is known to be involved in
      visually guided grasping. This region is also active during the observation of
      object manipulation by others. Here, we explore the nature of action
      representation using functional magnetic resonance imaging (fMRI). Fourteen
      subjects observed video clips showing object manipulation by the right or left
      hand. The clips were presented in either the right or left peripheral visual
      field. The fMRI activation in the occipital cortex and in the caudal sections of
      the parietal cortex was specific to the visual-field location of the clips. In
      contrast, the principal factor determining the response in anterior intraparietal
      cortex was the identity of the observed hand. Furthermore, these "hand-specific"
      parietal areas also showed contralateral hand specificity during self action
      (i.e., object manipulation) without visual feedback. A similar selectivity for
      the identity of the observed hand was seen when using a region of interest
      analysis, focusing on individually defined visuomotor voxels within the parietal
      cortex. This dual visuomotor grasping representation lends further evidence for
      the existence of a mirror system in humans and suggests that the anterior
      intraparietal cortex is involved in the specific motor simulation of hand
      actions.

PMID- 16988045
TI  - Netrin-1 signaling regulates de novo protein synthesis of kappa opioid receptor
      by facilitating polysomal partition of its mRNA.
AB  - The expression of kappa opioid receptor (KOR) is subjected to both
      transcriptional and posttranscriptional controls. We report that KOR translation
      is regulated by netrin-1 in primary neurons of dorsal root ganglion (DRG) and in
      P19 embryonal carcinoma cells. Without stimulation, a significant portion of KOR
      mRNA is maintained in a dormant state and partitions in the translationally
      inactive, post-polysomal fraction. During netrin-1 stimulation, which activates
      its downstream target focal adhesion kinase (FAK), KOR mRNA rapidly partitions to
      the translationally active polysomal fraction. Functionally, the newly
      synthesized KOR proteins in DRG neurons are able to bind to specific ligands.
      This report describes the first example of netrin-1 signaling in the
      translational control of a drug receptor KOR, which involves the mediator of
      netrin-1, FAK, and a novel mechanism that enhances the association of target mRNA
      with polysomes for translational activation.

PMID- 16988046
TI  - A specific survival response in dopamine neurons at most risk in Parkinson's
      disease.
AB  - The specific expression of fibroblast growth factor 20 (FGF-20) in the adult
      substantia nigra and the association between FGF-20 mutations and Parkinson's
      disease provoked exploration of the function of this growth factor. We show by
      gain- and loss-of-function in vitro experiments that FGF-20 promotes survival and
      stimulates dopamine (DA) release in a calbindin-negative subset of cells that are
      preferentially lost in Parkinson's disease. FGF-20 selectively activates tyrosine
      hydroxylase in calbindin-negative neurons. In the adult substantia nigra,
      calbindin-negative neurons specifically express high levels of FGFR1 (FGF
      receptor 1). These data show that FGF signals to elevate DA levels and protect
      the specific midbrain neuron type at most risk in Parkinson's patients.

PMID- 16988047
TI  - Integrated neural processes for defining potential actions and deciding between
      them: a computational model.
AB  - To successfully accomplish a behavioral goal such as reaching for an object, an
      animal must solve two related problems: to decide which object to reach and to
      plan the specific parameters of the movement. Traditionally, these two problems
      have been viewed as separate, and theories of decision making and motor planning
      have been developed primarily independently. However, neural data suggests that
      these processes involve the same brain regions and are performed in an integrated
      manner. Here, a computational model is described that addresses both the question
      of how different potential actions are specified and how the brain decides
      between them. In the model, multiple potential actions are simultaneously
      represented as continuous regions of activity within populations of cells in
      frontoparietal cortex. These representations engage in a competition for overt
      execution that is biased by modulatory influences from prefrontal cortex. The
      model neural populations exhibit activity patterns that correlate with both the
      spatial metrics of potential actions and their associated decision variables, in
      a manner similar to activities in parietal, prefrontal, and premotor cortex. The
      model therefore suggests an explanation for neural data that have been hard to
      account for in terms of serial theories that propose that decision making occurs
      before action planning. In addition to simulating the activity of individual
      neurons during decision tasks, the model also reproduces key aspects of the
      spatial and temporal statistics of human choices and makes a number of testable
      predictions.

PMID- 16988048
TI  - Peripheral myelin maintenance is a dynamic process requiring constant Krox20
      expression.
AB  - Onset of myelination in Schwann cells is governed by several transcription
      factors, including Krox20/Egr2, and mutations affecting Krox20 result in various
      human hereditary peripheral neuropathies, including congenital hypomyelinating
      neuropathy (CHN) and Charcot-Marie-Tooth disease (CMT). Similar molecular
      information is not available on the process of myelin maintenance. We have
      generated conditional Krox20 mutations in the mouse that allowed us to develop
      models for CHN and CMT. In the latter case, specific inactivation of Krox20 in
      adult Schwann cells results in severe demyelination, involving rapid Schwann cell
      dedifferentiation and increased proliferation, followed by an attempt to
      remyelinate and a block at the promyelinating stage. These data establish that
      Krox20 is not only required for the onset of myelination but that it is also
      crucial for the maintenance of the myelinating state. Furthermore, myelin
      maintenance appears as a very dynamic process in which Krox20 may constitute a
      molecular switch between Schwann cell myelination and demyelination programs.

PMID- 16988049
TI  - Identification of sequence motifs that target neuronal nicotinic receptors to
      dendrites and axons.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a family of ligand
      gated ion channels that play important roles in central and peripheral nervous
      systems. The subcellular distribution of neuronal nAChRs has important
      implications for function and is not well understood. Here, we analyzed the
      targeting of two major types of neuronal nAChRs by expressing epitope-tagged
      subunits in cultured hippocampal neurons. Surprisingly, the alpha7 nAChR (alpha7)
      and alpha4/beta2 nAChR (alpha4beta2) displayed distinct patterns of expression,
      with alpha7 targeted preferentially to the somatodendritic compartments, whereas
      alpha4beta2 was localized to both axonal and dendritic domains. When fused to CD4
      or IL2RA (interleukin 2 receptor alpha subunit) proteins, which are normally
      distributed ubiquitously, the M3-M4 intracellular loop from the alpha7 subunit
      promoted dendritic expression, whereas the homologous M3-M4 loop from the alpha4
      subunit led to surface axonal expression. Systemic screening and alanine
      substitution further identified a 25-residue leucine motif ([DE]XXXL[LI])
      containing an axonal targeting sequence within the alpha4 loop and a 48-residue
      dileucine and tyrosine motif (YXXO) containing a dendritic targeting sequence
      from the alpha7 loop. These results provide valuable information in understanding
      diverse roles of neuronal nAChRs in mediating and modulating synaptic
      transmission, synaptic plasticity, and nicotine addiction.

PMID- 16988050
TI  - Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide
      levels in experimental autoimmune encephalomyelitis models.
AB  - Axonal damage is a major morphological alteration in the CNS of patients with
      multiple sclerosis (MS) and its animal model, experimental autoimmune
      encephalomyelitis (EAE). However, the underlying mechanism for the axonal damage
      associated with MS/EAE and its contribution to the clinical symptoms remain
      unclear. The expression of a fusion protein, named "Wallerian degeneration slow"
      (Wld(S)), can protect axons from degeneration, likely through a beta-nicotinamide
      adenine dinucleotide (NAD)-dependent mechanism. In this study, we find that, when
      induced with EAE, Wld(S) mice showed a modest attenuation of behavioral deficits
      and axon loss, suggesting that EAE-associated axon damage may occur by a
      mechanism similar to Wallerian degeneration. Furthermore, nicotinamide (NAm), an
      NAD biosynthesis precursor, profoundly prevents the degeneration of demyelinated
      axons and improves the behavioral deficits in EAE models. Finally, we demonstrate
      that delayed NAm treatment is also beneficial to EAE models, pointing to the
      therapeutic potential of NAm as a protective agent for EAE and perhaps MS
      patients.

PMID- 16988051
TI  - Frontoparietal activity with minimal decision and control.
AB  - In the human brain, a well known frontoparietal circuit, including lateral
      prefrontal cortex (LPFC), presupplementary motor area/anterior cingulate cortex
      (pre-SMA/ACC), and both the superior and inferior parietal cortex, is involved in
      cognitive control. One proposal is that the frontoparietal cortex holds a
      flexible description of attended or task-relevant information, biasing processing
      in favor of this information in many different parts of the brain. Here, we
      separate frontoparietal coding of attended information from its active use in
      behavior. In two experiments, subjects watch a stream of visual stimuli in a
      fixed location. In the first experiment, there is no task to perform; in the
      second, decisions are orthogonal to the occurrence of new stimulus events. Even
      in these simple circumstances, we find that attended stimulus changes give
      extensive activation of LPFC, pre-SMA/ACC and parietal cortex, whereas unattended
      changes do not. Even without behavior to control, these classical "control"
      regions are active in simple update of attended information.

PMID- 16988052
TI  - Age-related changes in iron homeostasis and cell death in the cerebellum of
      ceruloplasmin-deficient mice.
AB  - Iron is essential for a variety of cellular functions, but its levels and
      bioavailability must be tightly regulated because of its toxic redox activity. A
      number of transporters, binding proteins, reductases, and ferroxidases help
      maintain iron homeostasis to prevent cell damage. The multi-copper ferroxidase
      ceruloplasmin (Cp) converts toxic ferrous iron to its nontoxic ferric form and is
      required for iron efflux from cells. Absence of this enzyme in humans leads to
      iron accumulation and neurodegeneration in the CNS. Here we report on the changes
      that occur in the cerebellum of Cp null (Cp-/-) mice with aging. We show that
      iron accumulation, which is reflected in increased ferritin expression, occurs
      mainly in astrocytes by 24 months in Cp-/- mice and is accompanied by a
      significant loss of these cells. In contrast, Purkinje neurons and the large
      neurons in the deep nuclei of Cp-/- mice do not accumulate iron but express high
      levels of the iron importer divalent metal transporter 1, suggesting that these
      cells may be iron deprived. This is also accompanied by a significant reduction
      in the number of Purkinje neurons. These data suggest that astrocytes play a
      central role in the acquisition of iron from the circulation and that two
      different mechanisms underlie the loss of astrocytes and neurons in Cp-/- mice.
      These findings provide a better understanding of the degenerative changes seen in
      humans with aceruloplasminemia and have implications for normal aging and
      neurodegenerative diseases in which iron accumulation occurs.

PMID- 16988053
TI  - Monkey sound localization: head-restrained versus head-unrestrained orienting.
AB  - The sound localization abilities of three rhesus monkeys were tested under head
      restrained and head-unrestrained conditions. Operant conditioning and the
      magnetic search coil technique were used to measure eye and head movements to
      sound sources. Whereas the results support previous findings that monkeys
      localize sounds very poorly with their heads restrained, the data also reveal for
      the first time that monkeys localize sounds much more accurately and with less
      variability when their heads are allowed to move. Control experiments using
      acoustic stimuli known to produce spatial auditory illusions such as summing
      localization confirmed that the monkeys based their orienting on localizing the
      sound sources and not on remembering spatial locations that resulted in rewards.
      Overall, the importance of using ecologically valid behaviors for studies of
      sensory processes is confirmed, and the potential of the rhesus monkey, the model
      closest to human, for studies of spatial auditory function, is established.

PMID- 16988054
TI  - Evaluation of the role of multidrug resistance-associated protein (Mrp) 3 and
      Mrp4 in hepatic basolateral excretion of sulfate and glucuronide metabolites of
      acetaminophen, 4-methylumbelliferone, and harmol in Abcc3-/- and Abcc4-/- mice.
AB  - Although glucuronide and sulfate conjugates of many drugs and endogenous
      compounds undergo appreciable hepatic basolateral excretion into sinusoidal
      blood, the mechanisms that govern basolateral translocation of these hydrophilic
      metabolites have not been completely elucidated. In the present study, the
      involvement in this process of Mrp3 and Mrp4, two basolateral efflux
      transporters, was evaluated by analyzing the hepatic basolateral excretion of the
      glucuronide and sulfate metabolites of acetaminophen, 4-methylumbelliferone, and
      harmol in Abcc3(-/-) and Abcc4(-/-) mice using a cassette dosing approach. In the
      livers of Abcc3(-/-) and Abcc4(-/-) mice, the basolateral excretory clearance of
      acetaminophen sulfate was reduced approximately 20 and approximately 20%, 4
      methylumbelliferyl sulfate was reduced approximately 50 and approximately 65%,
      and harmol sulfate was decreased approximately 30 and approximately 45%,
      respectively. The basolateral excretory clearance of acetaminophen glucuronide, 4
      methylumbelliferyl glucuronide, and harmol glucuronide was reduced by
      approximately 96, approximately 85, and approximately 40%, respectively, in the
      livers of Abcc3(-/-) mice. In contrast, basolateral excretory clearance of these
      glucuronide conjugates was unaffected by the absence of Mrp4. These results
      provide the first direct evidence that Mrp3 and Mrp4 participate in the hepatic
      basolateral excretion of sulfate conjugates, although additional mechanism(s) are
      likely involved. In addition, they reveal that Mrp3 mediates the hepatic
      basolateral excretion of diverse glucuronide conjugates.

PMID- 16988055
TI  - Sigma-1 receptor activation prevents intracellular calcium dysregulation in
      cortical neurons during in vitro ischemia.
AB  - Sigma receptors are putative targets for neuroprotection following ischemia;
      however, little is known on their mechanism of action. One of the key components
      in the demise of neurons following ischemic injury is the disruption of
      intracellular calcium homeostasis. Fluorometric calcium imaging was used to
      examine the effects of sigma receptor activation on changes in intracellular
      calcium concentrations ([Ca(2+)](i)) evoked by in vitro ischemia in cultured
      cortical neurons from embryonic rats. The sigma receptor agonist, 1,3-di-o-tolyl
      guanidine (DTG), was shown to depress [Ca(2+)](i) elevations observed in response
      to ischemia induced by sodium azide and glucose deprivation. Two sigma receptor
      antagonists, metaphit [1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine] and
      BD-1047 (N-[2-3,4-dichlorophenyl)-ethyl]-N-methyl-2-(dimethylamino)ethylamine),
      were shown to blunt the ability of DTG to inhibit ischemia-evoked increases in
      [Ca(2+)](i), revealing that the effects are mediated by activation of sigma
      receptors and not via the actions of DTG on nonspecific targets such as N-methyl
      d-aspartate receptors. DTG inhibition of ischemia-induced increases in
      [Ca(2+)](i) was mimicked by the sigma-1 receptor-selective agonists,
      carbetapentane, (+)-pentazocine and PRE-084 [2-(4-morpholinethyl) 1
      phenylcyclohexanecarboxylate hydrochloride], but not by the sigma-2-selective
      agonist, ibogaine, showing that activation of sigma-1 receptors is responsible
      for the effects. In contrast, DTG, carbetapentane, and ibogaine blocked
      spontaneous, synchronous calcium transients observed in our preparation at
      concentrations consistent with sigma receptor-mediated effects, indicating that
      both sigma-1 and sigma-2 receptors regulate events that affect [Ca(2+)](i) in
      cortical neurons. Our studies show that activation of sigma receptors can
      ameliorate [Ca(2+)](i) dysregulation associated with ischemia in cortical neurons
      and, thus, identify one of the mechanisms by which these receptors may exert
      their neuroprotective properties.

PMID- 16988056
TI  - Mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4h
      benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] prevents mucosal mast
      cell hyperplasia and intestinal dysmotility in experimental Trichinella spiralis
      inflammation in the rat.
AB  - Trichinella spiralis infection in rats induces hypermotility and an abnormal
      response to cholecystokinin (CCK) similar to motor disturbances observed in
      irritable bowel syndrome. Mast cell hyperplasia is also characteristic of this
      experimental model. The aim of our study was to correlate mast cell activity with
      the development of dysmotility and to demonstrate whether the mast cell
      stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2
      b]thiophen-10(9H)-one fumarate] could prevent the development of intestine
      hypermotility. Sprague-Dawley rats were infected with T. spiralis and, 5 days
      after infection, treated with the mast-cell stabilizer ketotifen (10 mg/kg/day).
      Twelve days after infection, intestinal spontaneous motor activity and response
      to CCK were evaluated by means of strain-gauge transducers. Immunohistochemistry
      for rat mast cell protease II (RMCPII), cyclooxygenase (COX)-2, and inducible
      nitric-oxide synthase (iNOS) was performed in intestinal specimens. In addition,
      RMCPII and myeloperoxidase were determined in serum. Infected control rats showed
      hypermotility, mast cell hyperplasia, increased RMCPII levels, increased
      myeloperoxidase, and overexpression of COX-2 and iNOS. In contrast, ketotifen
      treated rats showed spontaneous intestinal motility and CCK response similar to
      the noninfected control rats. Mast cell hyperplasia and RMCPII were reduced in
      ketotifen-treated rats. Inflammatory parameters were less modified by ketotifen,
      but those animals that received the longest ketotifen treatment showed a slight
      amelioration in these parameters. These results indicate that mast cells are
      implicated in the development of hypermotility. The treatment with ketotifen
      prevented hypermotility and mast cell hyperplasia and diminished mucosal mast
      cell activity.

PMID- 16988057
TI  - Efficacy of the world health organization analgesic ladder to treat pain in end
      stage renal disease.
AB  - Pain is the one of the most common symptoms experienced by patients with ESRD; it
      impairs their quality of life and is undertreated. Most pain clinicians believe
      that the pain management approach of the World Health Organization (WHO) three
      step analgesic ladder is applicable to the treatment of patients with ESRD, but
      this approach has not been validated for them. A cohort of 45 hemodialysis
      patients were assessed for type and severity of pain using the Short-Form McGill
      Pain Questionnaire and then treated during a 4-wk period according to the WHO
      analgesic ladder. Mean age was 65 +/- 12.5 yr, and 22 (49%) patients had diabetic
      nephropathy as the cause of ESRD. Initial pain was rated severe by 34 (76%)
      patients. There was no difference in initial pain rating by gender, age, race, or
      type of pain. Forty percent of patients reported nociceptive pain, 31%
      neuropathic, and 29% both. Adequate analgesia was achieved in 43 (96%) of 45
      patients. The mean pain score decreased from 7.8 +/- 1.2 to 1.6 +/- 1.3 (P <
      0.001). Patients who were 65 yr and older had higher posttreatment scores than
      those who were younger than 65 (2.1 +/- 1.4 versus 0.94 +/- 0.93; P = 0.002) and
      more medication adverse effects. It is concluded that the use of the WHO three
      step analgesic ladder leads to effective pain relief in hemodialysis patients.
      Older patients will need more careful pain management to achieve the same results
      as younger patients. Further studies are needed to confirm these results in a
      larger, more diverse dialysis population.

PMID- 16988058
TI  - Ischemic preconditioning provides both acute and delayed protection against renal
      ischemia and reperfusion injury in mice.
AB  - Acute as well as delayed ischemic preconditioning (IPC) provides protection
      against cardiac and neuronal ischemia reperfusion (IR) injury. This study
      determined whether delayed preconditioning occurs in the kidney and further
      elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four
      cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia
      either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed
      renal IPC provided powerful protection against renal IR injury. Inhibition of Akt
      but not extracellular signal-regulated kinase phosphorylation prevented the
      protection that was afforded by acute IPC. Neither extracellular signal-regulated
      kinase nor Akt inhibition prevented protection that was afforded by delayed renal
      IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to
      scavenge free radicals prevented the protection that was provided by acute but
      not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin
      sensitive G-proteins attenuated protection from both acute and delayed renal IPC.
      Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as
      heat-shock protein 27 synthesis, and the renal protective effects of delayed
      preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1
      iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice.
      Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a
      selective A(1)AR antagonist failed to block preconditioning and acute and delayed
      preconditioning occurred in mice that lacked A(1)AR. Therefore, this study
      demonstrated that acute or delayed IPC provides renal protection against IR
      injury in mice but involves distinct signaling pathways.

PMID- 16988059
TI  - Modified glomerular filtration rate estimating equation for Chinese patients with
      chronic kidney disease.
AB  - The Modification of Diet in Renal Disease (MDRD) equations provide a rapid method
      of assessing GFR in patients with chronic kidney disease (CKD). However, previous
      research indicated that modification of these equations is necessary for
      application in Chinese patients with CKD. The objective of this study was to
      modify MDRD equations on the basis of the data from the Chinese CKD population
      and compare the diagnostic performance of the modified MDRD equations with that
      of the original MDRD equations across CKD stages in a multicenter, cross
      sectional study of GFR estimation from plasma creatinine, demographic data, and
      clinical characteristics. A total of 684 adult patients with CKD, from nine
      geographic regions of China were selected. A random sample of 454 of these
      patients were included in the training sample set, and the remaining 230 patients
      were included in the testing sample set. With the use of the dual plasma sampling
      (99m)Tc-DTPA plasma clearance method as a reference for GFR measurement, the
      original MDRD equations were modified by two methods: First, by adding a racial
      factor for Chinese in the original MDRD equations, and, second, by applying
      multiple linear regression to the training sample and modifying the coefficient
      that is associated with each variable in the original MDRD equations and then
      validating in the testing sample and comparing it with the original MDRD
      equations. All modified MDRD equations showed significant performance improvement
      in bias, precision, and accuracy compared with the original MDRD equations, and
      the percentage of estimated GFR that did not deviate >30% from the reference GFR
      was >75%. The modified MDRD equations that were based on the Chinese patients
      with CKD offered significant advantages in different CKD stages and could be
      applied in clinical practice, at least in Chinese patients with CKD.

PMID- 16988060
TI  - Functional variants in the lymphotoxin-alpha gene predict cardiovascular disease
      in dialysis patients.
AB  - TNF-beta that is encoded by lymphotoxin-alpha gene (LTA) regulates adhesion
      molecules and IL-6. Previously, a genome-wide case-control study showed that LTA
      gene variants predisposed to cardiovascular disease (CVD). In a prospective study
      of 775 dialysis patients, LTA and IL-6 gene variants were tested as independent
      predictors of CVD risk. Four polymorphisms in the LTA gene and one in the IL-6
      gene were genotyped. CVD events were ascertained from medical records. During a
      mean follow-up of 2.6 yr, 294 first-incident CVD events occurred. The LTA 26Asn
      variant predicted higher adjusted CVD risk (hazard ratio HR 1.33 for each
      additional copy of Asn allele; 95% confidence interval 1.14 to 1.55; P = 0.0003).
      Two other nonsynonymous polymorphisms in the LTA, 13Agr and 51Pro, were
      associated with lower inflammatory activity and CVD risk. LTA haplotypes (based
      on all four single-nucleotide polymorphisms) were associated with inflammatory
      markers and predicted CVD risk (P = 0.005) after adjustment. These LTA genotype
      associations were independent of the IL-6 -174G/C genotype association that was
      reported recently. LTA and IL-6 gene variants independently predicted risk for
      CVD among dialysis patients, suggesting that susceptibility in multiple
      inflammatory pathways contribute to the development of CVD.

PMID- 16988061
TI  - Isolation and characterization of kidney-derived stem cells.
AB  - Acute kidney injury is followed by regeneration of damaged renal tubular
      epithelial cells. The purpose of this study was to test the hypothesis that renal
      stem cells exist in the adult kidney and participate in the repair process. A
      unique population of cells that behave in a manner that is consistent with a
      renal stem cell were isolated from rat kidneys and were termed multipotent renal
      progenitor cells (MRPC). Features of these cells include spindle-shaped
      morphology; self-renewal for >200 population doublings without evidence for
      senescence; normal karyotype and DNA analysis; and expression of vimentin, CD90
      (thy1.1), Pax-2, and Oct4 but not cytokeratin, MHC class I or II, or other
      markers of more differentiated cells. MRPC exhibit plasticity that is
      demonstrated by the ability of the cells to be induced to express endothelial,
      hepatocyte, and neural markers by reverse transcriptase-PCR and
      immunohistochemistry. The cells can differentiate into renal tubules when
      injected under the capsule of an uninjured kidney or intra-arterially after renal
      ischemia-reperfusion injury. Oct4 expression was seen in some tubular cells in
      the adult kidney, suggesting these cells may be candidate renal stem cells. It is
      proposed that MRPC participate in the regenerative response of the kidney to
      acute injury.

PMID- 16988062
TI  - Risk equation determining unsuccessful cannulation events and failure to
      maturation in arteriovenous fistulas (REDUCE FTM I).
AB  - Fistulas are the preferred permanent hemodialysis vascular access but a
      significant obstacle to increasing their prevalence is the fistula's high
      "failure to mature" (FTM) rate. This study aimed to (1) identify preoperative
      clinical characteristics that are predictive of fistula FTM and (2) use these
      predictive factors to develop and validate a scoring system to stratify the
      patient's risk for FTM. From a derivation set of 422 patients who had a first
      fistula created, a prediction rule was created using multivariate stepwise
      logistic regression. The model was internally validated using split-half cross
      validation and bootstrapping techniques. A simple scoring system was derived and
      externally validated on 445 different, prospective patients who received a new
      fistula at five large North American dialysis centers. The clinical predictors
      that were associated with FTM were aged > or =65 yr (odds ratio [OR] 2.23; 95%
      confidence interval [CI] 1.25 to 3.96), peripheral vascular disease (OR 2.97; 95%
      CI 1.34 to 6.57), coronary artery disease (OR 2.83; 95% CI 1.60 to 5.00), and
      white race (OR 0.43; 95% CI 0.24 to 0.75). The resulting scoring system, which
      was externally validated in 445 patients, had four risk categories for fistula
      FTM: low (24%), moderate (34%), high (50%), and very high (69%; trend P <
      0.0001). A preoperative, clinical prediction rule to determine fistulas that are
      likely to fail maturation was created and rigorously validated. It was found to
      be simple and easily reproducible and applied to predictive risk categories.
      These categories predicted risk of FTM to be 24, 34, 50, and 69% and are
      dependent on age, coronary artery disease, peripheral vascular disease, and race.
      The clinical utility of these risk categories in increasing rates of permanent
      accesses requires further clinical evaluation.

PMID- 16988063
TI  - Blockade of vascular endothelial growth factor signaling ameliorates diabetic
      albuminuria in mice.
AB  - For investigation of how the vascular endothelial growth factor (VEGF) system
      participates in the pathogenesis of diabetic kidney disease, type 2 diabetic
      db/db and control db/m mice were treated intraperitoneally with vehicle or 2
      mg/kg of a pan-VEGF receptor tyrosine kinase inhibitor, SU5416, twice a week for
      8 wk. Efficacy of SU5416 treatment in the kidney was verified by the inhibition
      of VEGF receptor-1 phosphorylation. Glomerular VEGF immunostaining, normally
      increased in diabetes, was unaffected by SU5416. Plasma creatinine did not change
      with diabetes or SU5416 treatment. The primary end point of albuminuria increased
      approximately four-fold in the diabetic db/db mice but was significantly
      ameliorated by SU5416. Correlates of albuminuria were investigated. Diabetic
      glomerular basement membrane thickening was prevented in the SU5416-treated db/db
      mice, whereas mesangial matrix expansion remained unchanged by treatment. The
      density of open slit pores between podocyte foot processes was decreased in db/db
      diabetes but was partly increased toward normal by SU5416. Finally, nephrin
      protein by immunofluorescence was decreased in the db/db mice but was
      significantly restored by SU5416. Paradoxically, total nephrin protein by
      immunoblotting was increased in diabetes, pointing toward a possible
      dysregulation of nephrin trafficking. Diabetic albuminuria is partially a
      function of VEGF receptor signaling overactivity. VEGF signaling was found to
      affect a number of podocyte-driven manifestations such as GBM thickening, slit
      pore density, and nephrin quantity, all of which are associated with the extent
      of diabetic albuminuria. By impeding these pathophysiologic processes, VEGF
      receptor inhibition by SU5416 might become a useful adjunct to anti-albuminuria
      therapy in diabetic nephropathy.

PMID- 16988064
TI  - Validation of creatinine-based estimates of GFR when evaluating risk factors in
      longitudinal studies of kidney disease.
AB  - Whereas much research has investigated equations for obtaining estimated GFR
      (eGFR) from serum creatinine in cross-sectional settings, little attention has
      been given to validating these equations as outcomes in longitudinal studies of
      chronic kidney disease. A common objective of chronic kidney disease studies is
      to identify risk factors for progression, characterized by slope (rate of change
      over time) or time to event (time until a designated decline in kidney function
      or ESRD). The relationships of 35 baseline factors with eGFR-based outcomes were
      compared with the relationships of the same factors with iothalamate GFR (iGFR)
      based outcomes in the African American Study of Kidney Disease and Hypertension
      (AASK; n = 1094). With the use of the AASK equation to calculate eGFR, results
      were compared between time to halving of eGFR or ESRD and time to halving of iGFR
      or ESRD (with effect sizes expressed per 1 SD) and between eGFR and iGFR slopes
      starting 3 mo after randomization. The effects of the baseline factors were
      similar between the eGFR- and iGFR-based time-to-event outcomes (Pearson R =
      0.99, concordance R = 0.98). Small but statistically significant differences (P <
      0.05, without adjustment for multiple analyses) were observed for seven of the 35
      factors. Agreement between eGFR and iGFR was somewhat weaker, although still
      relatively high for slope-based outcomes (Pearson R = 0.93, concordance R =
      0.92). Effects of covariate adjustment for age, gender, baseline GFR, and urine
      proteinuria also were similar between the eGFR and iGFR outcomes. Sensitivity
      analyses including death in the composite time-to-event outcomes or using the
      Modification of Diet in Renal Disease equation instead of the AASK equation
      provided similar results. In conclusion, the data from the AASK provide tentative
      support for use of outcomes that are based on an established eGFR formula using
      serum creatinine as a surrogate for measured iGFR-based outcomes in analyses of
      risk factors for the progression of kidney disease.

PMID- 16988065
TI  - Revisiting survival differences by race and ethnicity among hemodialysis
      patients: the Dialysis Outcomes and Practice Patterns Study.
AB  - Hemodialysis (HD) patients who are identified as belonging to racial or ethnic
      minority groups have longer survival than non-Hispanic white HD patients. This
      study sought to determine to what extent this survival difference is explained by
      comprehensive adjustment for measurable case-mix and treatment characteristics. A
      cohort analysis was conducted among 6677 patients between 1996 and 2001 in the
      American arm of the first phase of the Dialysis Outcomes and Practice Patterns
      Study, a prospective observational study. Using multivariable proportional
      hazards analysis, all-cause mortality by racial/ethnic category was compared
      before and after adjustment for other patient-level variables that are associated
      with mortality. Factors that influence the statistical associations of
      race/ethnicity with mortality were explored. The statistically significant (P <
      0.001) associations of racial/ethnic minority categories with lower mortality in
      unadjusted analyses were attenuated or lost in the multivariable model. Compared
      with non-Hispanic white patients, the adjusted hazard ratio (HR) (95% confidence
      interval [CI]) for mortality was 0.86 (0.72 to 1.03) for Hispanic patients; among
      non-Hispanic patients, the HR (95% CI) were 0.97 (0.85 to 1.11) for black
      patients, 0.82 (0.56 to 1.20) for Asian patients, 0.95 (0.52 to 1.73) for Native
      American patients, and 0.95 (0.60 to 1.50) for patients of other races (overall P
      = 0.66). The survival advantages for racial/ethnic minority categories were
      explained most notably by the combined influence of unbalanced distributions of
      numerous demographic, morbidity, nutritional, and laboratory variables. The
      associations of race/ethnicity with survival varied little by duration of ESRD
      and were not influenced substantially by different rates of kidney
      transplantation among patients who were on HD. The survival advantages for racial
      and ethnic minority groups on HD are explained largely by measurable case-mix and
      treatment characteristics. Individual racial minority group or Hispanic patients
      should not be expected to survive longer on HD than non-Hispanic white patients
      with similar clinical attributes.

PMID- 16988066
TI  - HIV-1 genes vpr and nef synergistically damage podocytes, leading to
      glomerulosclerosis.
AB  - This study aimed to identify the causative gene for HIV-1 associated nephropathy,
      a paradigmatic podocytopathy. A previous study demonstrated that transgenic
      expression of nonstructural HIV-1 genes selectively in podocytes in mice with
      FVB/N genetic background resulted in podocyte injury and glomerulosclerosis. In
      this study, transgenic mice that expressed individual HIV-1 genes in podocytes
      were generated. Five of six transgenic mice that expressed vpr developed podocyte
      damage and glomerulosclerosis. Analysis of an established vpr transgenic line
      revealed that transgenic mice on FVB/N but not on C57BL/6 genetic background
      developed podocyte injury by 8 wk of age, with later glomerulosclerosis. Four of
      11 transgenic mice that expressed nef also developed podocyte injury. One
      transgenic line was established from the nef founder mouse with the mildest
      phenotype. Transgenic mice in this line developed mesangial expansion at 3 wk of
      age and mild focal podocyte damage at 10 wk of age. Mating with FVB/N mice did
      not augment nephropathy. None of the transgenic mice that expressed vif, tat,
      rev, or vpu in podocytes, even with the FVB/N genetic background, developed
      podocyte injury. For testing effects of simultaneous expression of vpr and nef,
      these two lines were mated. All nef:vpr double-transgenic mice showed severe
      podocyte injury and glomerulosclerosis by 4 wk of age. In contrast, all vpr or
      nef single-transgenic mice in the same litter uniformly showed no or much milder
      podocyte injury. These findings indicate that vpr and nef each can induce
      podocyte injury with a prominent synergistic interaction.

PMID- 16988067
TI  - CD4+CD25+ regulatory T cells protect against injury in an innate murine model of
      chronic kidney disease.
AB  - Studies of mechanisms of disease regulation by CD4+CD25+ regulatory T cells
      (Treg) have been focused on their interaction with effector T cells; however, the
      possibility that regulation might involve noncognate cells has not been explored
      in detail. This study investigated the effect of CD4+CD25+ Treg on macrophage
      proinflammatory properties and phenotype in vitro and found that they modulate
      macrophages by inhibiting their activation, leading to reduced proinflammatory
      cytokine production and a downregulated effector phenotype. For testing the in
      vivo significance of this effect, CD4+CD25+ T cells that expressed high levels of
      Foxp3 were reconstituted into SCID mice after induction of Adriamycin
      nephropathy, a noncognate model of chronic renal disease. CD4+CD25+ T cells
      significantly reduced glomerular and interstitial injury. In addition, there was
      a significant fall in the number of macrophages in both the glomeruli and
      interstitium of SCID mice that were reconstituted with Treg as compared with the
      Adriamycin alone group. Blockade of TGF-beta using neutralizing antibodies
      significantly impaired the protective effect of Treg. These findings delineate a
      TGF-beta-dependent Treg-macrophage inhibitory interaction that can explain
      cognate-independent protection by Treg.

PMID- 16988068
TI  - The association of mood with quality of life ratings in epilepsy.
AB  - OBJECTIVE: To determine the relative contributions of psychological (mood and
      anxiety), social, and seizure-related variables to quality of life (QOL) scores
      in epilepsy. METHODS: Outpatients (n = 435) with epilepsy completed the Quality
      of Life in Epilepsy 31 Inventory (QOLIE-31), Beck Depression Inventory II (BDI
      II), Beck Anxiety Inventory, and a social survey. Stepwise linear regression and
      general linear model analyses determined the set of best predictors and the most
      unique predictors of composite QOLIE-31 score and subscale scores. RESULTS: A
      three-variable model accounted for 56% of the variance for the composite QOLIE-31
      score. The BDI-II was the strongest (often by several multiples in terms of
      variance explained) and most consistent predictor of the composite and QOLIE
      subscales in both types of analytic approaches. In no case did BDI-II
      significantly interact with the other variables, suggesting that its effect on
      QOL was direct and not mediated by other factors. Throughout the results,
      depression had an inverse relation to scores, i.e., lower levels of depression
      correlated with high QOL scores. Separate correlational analyses showed that poor
      seizure control was associated with increased numbers of depressive symptoms.
      DISCUSSION: Quality of Life in Epilepsy (QOLIE) scores, reflecting both general
      and specific aspects of quality of life, are strongly influenced by mood state,
      such as depression. Factors such as seizure control exert a more limited effect
      on the QOLIE. Health-related quality of life measures are needed in which mood
      does not play such a dominant role.

PMID- 16988069
TI  - Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy.
AB  - BACKGROUND: Inherited erythermalgia (also termed "erythromelalgia"),
      characterized by episodic burning pain in the distal extremities evoked by
      warmth, has been causally linked with mutations of the Na(v)1.7 sodium channel,
      which is preferentially expressed in nociceptors. Thus far, Na(v)1.7 mutations
      within intracellular linker parts of the channel have been physiologically
      characterized. OBJECTIVE: To investigate a Na(v)1.7 erythermalgia mutation that
      substitutes one uncharged amino acid for another within an S4 segment. METHODS:
      Whole-cell patch-clamp analysis was used to study biophysical properties of wild
      type and mutant (F216S) Na(v)1.7 channels in mammalian cells. RESULTS: The F216S
      mutation hyperpolarizes the voltage dependence of activation by 11 mV,
      accelerates activation, slows deactivation, and enhances the response to slow,
      small depolarizations. CONCLUSION: These results provide a physiologic basis for
      the linkage to erythermalgia of an Na(v)1.7 mutation that substitutes one
      uncharged residue for another within an S4 segment of the channel. These changes
      should increase excitability of nociceptive dorsal root ganglion neurons in which
      the mutant channel is present, thus contributing to pain.

PMID- 16988070
TI  - The evolution of very-low-calorie diets: an update and meta-analysis.
AB  - OBJECTIVE: Very-low-calorie diets (VLCDs), providing <800 kcal/d, have been used
      since the 1970s to induce rapid weight loss. Previous reviews of the literature
      have disagreed concerning the relative efficacy of VLCDs vs. conventional low
      calorie diets (LCDs) for achieving long-term weight loss. RESEARCH METHODS AND
      PROCEDURES: We sought to update findings on the clinical use, safety, and
      efficacy of VLCDs and to perform a meta-analysis of randomized trials that
      compared the long-term efficacy of LCDs and VLCDs. Original research articles
      were retrieved by a Medline search and from prior reviews of VLCDs. Trials were
      included only if they were randomized comparisons of LCDs and VLCDs and included
      a follow-up assessment at least 1 year after maximum weight loss. Data were
      abstracted by both authors regarding: duration of VLCD, total length of
      treatment, attrition, short- and long-term weight loss, changes in weight-related
      comorbidities, and adverse effects. RESULTS: Six randomized trials were found
      that met inclusion criteria. VLCDs, compared with LCDs, induced significantly
      greater short-term weight losses (16.1 +/- 1.6% vs. 9.7 +/- 2.4% of initial
      weight, respectively; p = 0.0001) but similar long-term losses (6.3 +/- 3.2% vs.
      5.0 +/- 4.0%, respectively; p > 0.2). Attrition was similar with VLCD and LCD
      regimens. DISCUSSION: VLCDs did not produce greater long-term weight losses than
      LCDs. In the United States, the use of liquid meal replacements as part of a 1000
      to 1500 kcal/d diet may provide an effective and less expensive alternative to
      VLCDs. In Europe, VLCDs are used with less intensive medical supervision than in
      the United States, which reduces the cost of this approach.

PMID- 16988071
TI  - Effect of exercise on hepatic gene expression in an obese mouse model using cDNA
      microarrays.
AB  - To understand the molecular mechanisms involved in the effect of exercise
      training, we examined hepatic transcriptional profiles using cDNA microarrays in
      exercise-trained and untrained mice with diet-induced obesity. C57BL/6J male mice
      (n = 10/group) were fed with a normal diet, high-fat diet (HFD), or HFD with
      exercise training for 12 weeks. The expression level of approximately 10,000
      transcripts in liver tissues from each group was assessed using cDNA microarray
      analysis. Exercise training improved lipid profiles and hepatic steatosis and
      decreased body fat mass induced by the HFD. Seventy-three genes were
      differentially expressed in the HFD- and/or HFD with exercise training-treated
      groups, compared with the normal diet- and HFD-fed groups, respectively.
      Interestingly, the expression profiles involved in metabolism, such as elongation
      of very long chain fatty acids-like 2, lipin, and malic enzyme, were changed by
      exercise training. In addition, expression of genes altered by exercise training
      related to defense and stress response, including metallothionein 1 and 2 and
      heat shock protein, showed interesting findings. Our study showed beneficial
      effects of exercise training in preventing the development of obesity and
      metabolic disorders in mice with diet-induced obesity.

PMID- 16988072
TI  - Modulation and lack of cross-talk between signal transducer and activator of
      transcription 5 and Suppressor of cytokine signaling-3 in insulin and growth
      hormone signaling in 3T3-L1 adipocytes.
AB  - OBJECTIVE: To examine the role of signal transducer and activator of
      transcription (STAT) 5 and suppressor of cytokine signaling (SOCS)-3 in the cross
      talk between growth hormone and insulin (INS) signaling in fat cells. RESEARCH
      METHODS AND PROCEDURES: Fully differentiated 3T3-L1 adipocytes were exposed to
      INS, growth hormone (GH), or both of these growth factors, and the activation of
      STAT5 proteins and mitogen-activated protein kinase was examined using phospho
      specific antibodies. The induction of SOCS-3 mRNA was assessed by Northern blot
      analysis. INS-stimulated glucose transport was also measured. RESULTS: We
      observed that GH, not INS, induced STAT5 activation in adipocytes in a manner
      that was independent of extracellular signal-regulated kinase (ERK) activation or
      new protein synthesis. GH strongly induced SOCS-3 mRNA expression, whereas INS
      had a much less potent effect on SOCS-3 mRNA expression. Because SOCS-3 has been
      implicated in the attenuation of GH and INS signaling, we examined the cross-talk
      between these signaling pathways. GH pretreatment of adipocytes inhibited GH
      signaling. Similarly, INS pretreatment inhibited INS signaling. However, INS did
      not block the GH-induced activation of STAT5, and GH did not block the INS
      induction of ERK activity or of increased glucose uptake. We observed that
      neither new protein synthesis nor activation of ERKs 1 and 2 were required for
      the inhibition of GH signaling. DISCUSSION: These results demonstrate that
      blocking the induction of the SOCS-3 protein has no effect on the attenuation of
      GH signaling and support recent studies suggesting that SOCS proteins have
      additional functions. In addition, these studies demonstrate that GH-induced SOCS
      3 expression is insufficient to inhibit INS-induced glucose uptake in adipocytes.

PMID- 16988073
TI  - Central leptin gene therapy blocks ovariectomy-induced adiposity.
AB  - OBJECTIVE: In this study, we tested the hypothesis that insufficiency of leptin
      restraint in the hypothalamus is responsible for promoting weight gain and
      adiposity after ovariectomy (ovx). Whether increasing leptin transgene expression
      can overcome the diminution in leptin restraint was evaluated in ovx rats.
      RESEARCH METHODS AND PROCEDURES: Enhanced leptin or green fluorescent protein
      (GFP; control) transgene expression was induced by a single
      intracerebroventricular injection of recombinant adeno-associated viral vector
      encoding either leptin gene (rAAV-lep) or GFP gene (rAAV-GFP; control) in acutely
      and chronically ovx rats. Body weight and food intake responses were monitored
      weekly. White adipose tissue (WAT) mass and serum levels of WAT-derived hormones,
      leptin, and adiponectin were analyzed at termination of the experiments. RESULTS
      AND DISCUSSION: An increase in leptin transgene expression in the hypothalamus
      initiated soon after ovx blocked hyperphagia and body weight gain and markedly
      suppressed WAT mass and adipokines, leptin, and adiponectin. Similar suppression
      of weight gain and adiposity and serum leptin and adiponectin levels after
      intracerebroventricular rAAV-lep injection in chronically ovx rats were observed
      concomitant with unchanged daily food intake. These findings are consistent with
      the hypothesis that in the absence of ovarian steroids, the existent
      insufficiency of leptin restraint at the hypothalamic level can be overcome with
      ectopic leptin expression, thereby reinstating central control on weight and
      adiposity.

PMID- 16988074
TI  - Plasma adipokines and body composition in response to modest dietary
      manipulations in the mouse.
AB  - OBJECTIVE: The relationship between adipokine levels and body composition has not
      been carefully examined. Most studies in humans are cross-sectional, and the few
      studies in mice have been restricted to a comparison of control animals with
      markedly obese, insulin-resistant mice. Our objective was to study changes in
      adipokine levels and body composition in response to modest dietary intervention.
      RESEARCH METHODS AND PROCEDURES: Plasma resistin, adiponectin, and leptin levels
      were examined in mice fed ad libitum, a 75% restricted diet, or a diet
      supplemented with 10% sucrose. Body composition was determined by whole-body DXA.
      RESULTS: The percentage body fat was reduced in mice subjected to the restricted
      diet and increased in mice supplemented with 10% dextrose. Adipokine levels were
      not different in either of these groups compared with the control mice. A
      significant inverse correlation was observed between resistin levels and total
      body fat, whereas there was no significant correlation between body fat and
      adiponectin levels. Positive correlations were observed between leptin levels and
      percentage body fat, total body fat, and abdominal fat. Leptin levels correlated
      with plasma glucose, but multivariate analysis revealed that this correlation was
      the result of a strong positive correlation between leptin and insulin levels.
      There were no correlations between glycemia and resistin or glycemia and
      adiponectin levels, and no correlation was observed between any of the adipokine
      levels and bone mineral content or density. DISCUSSION: These data suggest that
      in the mouse, modest dietary perturbations have little effect on resistin and
      adiponectin levels despite significant effects on glycemia, insulin levels, and
      bone parameters.

PMID- 16988075
TI  - The importance of catch-up growth after early malnutrition for the programming of
      obesity in male rat.
AB  - OBJECTIVE: To investigate whether catch-up growth after maternal malnutrition
      would favor the development of obesity in adulthood. RESEARCH METHODS AND
      PROCEDURES: Pregnant rats were submitted to protein or calorie restriction during
      the course of gestation. During lactation, pups were protein-restricted, normally
      fed, or overfed [reduced litter size, control (C) diet]. At weaning, rats were
      transferred to chow or to a hypercaloric diet (HCD) known to induce obesity. Body
      weight, food intake, blood parameters, glucose tolerance, adipocyte cellularity,
      and adipose factors contributing to cardiovascular disease development were
      measured. RESULTS: Protein and calorie restriction during gestation led to growth
      retardation at birth. If malnutrition was prolonged throughout lactation, adult
      body weight was permanently reduced. However, growth-retarded offspring overfed
      during the suckling period underwent a rapid catch-up growth and became heavier
      than the normally fed Cs. Offspring of calorie-restricted rats gained more weight
      than those of dams fed protein-restricted diet. Feeding an HCD postnatally
      amplified the effect of calorie restriction, and offspring that underwent catch
      up growth became more obese than Cs. The HCD was associated with hyperphagia,
      hyperglycemia, hyperinsulinemia, glucose intolerance, insulin resistance, and
      adipocyte hypertrophy. The magnitude of effects varied depending on the type and
      the timing of early malnutrition. The expression of genes encoding factors
      implicated in cardiovascular disease was also modulated differently by early
      malnutrition and adult obesity. DISCUSSION: Catch-up growth immediately after
      early malnutrition should be a key point for the programming of obesity.

PMID- 16988076
TI  - Very low-carbohydrate versus isocaloric high-carbohydrate diet in dietary obese
      rats.
AB  - OBJECTIVE: The effects of a very low-carbohydrate (VLC), high-fat (HF) dietary
      regimen on metabolic syndrome were compared with those of an isocaloric high
      carbohydrate (HC), low-fat (LF) regimen in dietary obese rats. RESEARCH METHODS
      AND PROCEDURES: Male Sprague-Dawley rats, made obese by 8 weeks ad libitum
      consumption of an HF diet, developed features of the metabolic syndrome vs. lean
      control (C) rats, including greater visceral, subcutaneous, and hepatic fat
      masses, elevated plasma cholesterol levels, impaired glucose tolerance, and
      fasting and post-load insulin resistance. Half of the obese rats (VLC) were then
      fed a popular VLC-HF diet (Weeks 9 and 10 at 5% and Weeks 11 to 14 at 15%
      carbohydrate), and one-half (HC) were pair-fed an HC-LF diet (Weeks 9 to 14 at
      60% carbohydrate). RESULTS: Energy intakes of pair-fed VLC and HC rats were less
      than C rats throughout Weeks 9 to 14. Compared with HC rats, VLC rats exhibited
      impaired insulin and glycemic responses to an intraperitoneal glucose load at
      Week 10 and lower plasma triacylglycerol levels but retarded loss of hepatic,
      retroperitoneal, and total body fat at Week 14. VLC, HC, and C rats no longer
      differed in body weight, plasma cholesterol, glucose tolerance, or fasting
      insulin resistance at Week 14. Progressive decreases in fasting insulin
      resistance in obese groups paralleled concomitant reductions in hepatic,
      retroperitoneal, and total body fat. DISCUSSION: When energy intake was matched,
      the VLC-HF diet provided no advantage in weight loss or in improving those
      components of the metabolic syndrome induced by dietary obesity and may delay
      loss of hepatic and visceral fat as compared with an HC-LF diet.

PMID- 16988077
TI  - Mesenteric adipose tissue-derived monocyte chemoattractant protein-1 plays a
      crucial role in adipose tissue macrophage migration and activation in obese mice.
AB  - OBJECTIVE: To determine whether chemokines, which play a pivotal role in
      monocyte/macrophage trafficking, modulate macrophage infiltration into and
      activation in the adipose tissues. RESEARCH METHODS AND PROCEDURES: Various types
      of adipose tissue were isolated from different fat depots (e.g., mesenteric,
      epididymal, renal, and subcutaneous adipose tissues) from obese mice fed a high
      fat diet and from non-obese controls fed a standard diet. The isolated tissues
      were cultured for 24, 48, and 72 hours. The level of monocyte chemoattractant
      protein-1 (MCP-1) expression and the amount of protein released were measured by
      reverse transcriptase-polymerase chain reaction or enzyme-linked immunosorbent
      assay, respectively. Chemotaxis assay was performed to measure the degree of
      macrophage migration. Macrophage activation was estimated by measuring the
      concentrations of nitric oxide and tumor necrosis factor alpha. RESULTS: The
      level of MCP-1 mRNA expression, protein content, and the amount of protein
      released significantly increased in the adipose tissues from the obese mice
      compared with those from the non-obese mice. The mesenteric adipose tissue
      produced the highest levels of MCP-1 protein among the four different fat depots.
      Mesenteric adipose tissue-conditioned medium induced the highest degree of
      macrophage migration and strongly induced macrophages to produce proinflammatory
      mediators such as nitric oxide and tumor necrosis factor alpha. The
      neutralization of MCP-1 in the adipose tissue-conditioned medium significantly
      inhibited the migration and activation of macrophages. DISCUSSION: Our findings
      suggest that MCP-1 plays a crucial role in adipose tissue inflammatory response
      by activating and inducing the infiltration of macrophages into adipose tissues.
      MCP-1 may be closely associated with visceral obesity-related complications and,
      thus, may be a useful therapeutic target for modulating visceral obesity-related
      diseases.

PMID- 16988078
TI  - Peripheral mechanisms of sibutramine involving proximal gastric motility in dogs.
AB  - OBJECTIVE: Sibutramine, a serotonin-norepinephrine uptake inhibitor, has been
      used for treating obesity. However, its possible mechanisms involving gastric
      motility have not been reported. The aim of this study was to evaluate the
      effects of sibutramine on gastric accommodation and antral motility. RESEARCH
      METHODS AND PROCEDURES: The study was performed in seven dogs with a stomach
      cannula and composed of two separate experiments: antral contractions and gastric
      tone. Each experiment included two sessions on 2 separate days in a randomized
      order: a control session and a treatment session with sibutramine (5 mg/kg per
      os) administrated 2 hours before the study. RESULTS: Sibutramine significantly
      increased fasting gastric tone; the gastric volume in the fasting state at
      baseline was 103.8 +/- 12.3 mL and significantly decreased to 35.3 +/- 16.0 mL
      with sibutramine (p = 0.0075). Sibutramine also impaired gastric accommodation.
      The average postprandial gastric volume was 472.1 +/- 16.7 mL in the control
      session and reduced to 302.2 +/- 53.6 mL with sibutramine (p = 0.013). The
      average postprandial increase in gastric volume during the 60-minute postprandial
      period with sibutramine was significantly lower than the corresponding values in
      the control session: 266.8 +/- 46.1 vs. 393.9 +/- 15.3 mL (p = 0.03). Sibutramine
      had no effects on postprandial antral contractions. DISCUSSION: Sibutramine
      increases gastric tone and impairs gastric accommodation to an orally ingested
      meal. The inhibitory effect of sibutramine on gastric accommodation may partially
      explain the reduced food intake with sibutramine in patients with obesity.

PMID- 16988079
TI  - A physiological role of breast milk leptin in body weight control in developing
      infants.
AB  - OBJECTIVE: Leptin, a hormone that regulates food intake and energy metabolism, is
      present in breast milk. The aim of this study was to determine whether milk
      leptin concentration is correlated with maternal circulating leptin and BMI and
      with body weight gain of infants. RESEARCH METHODS AND PROCEDURES: A group of 28
      non-obese women (BMI between 16.3 and 27.3 kg/m(2)) who breast-fed their infants
      for at least 6 months and their infants were studied. Venous blood and milk
      samples were obtained from mothers at 1, 3, 6, and 9 months of lactation, and
      leptin concentration was determined. Infant body weight and height were followed
      until 2 years of age. RESULTS: During the whole lactation period, milk leptin
      concentration correlated positively with maternal plasma leptin concentration and
      with maternal BMI. In addition, milk leptin concentration at 1 month of lactation
      was negatively correlated with infant BMI at 18 and 24 months of age. A better
      negative correlation was also found between log milk leptin concentration at 1
      and at 3 months of lactation and infant BMI from 12 to 24 months of age.
      DISCUSSION: We concluded that, in a group of non-obese mothers, infant body
      weight during the first 2 years may be influenced by milk leptin concentration
      during the first stages of lactation. Thus, moderate milk-borne maternal leptin
      appears to provide moderate protection to infants from an excess of weight gain.
      These results seem to point out that milk leptin is an important factor that
      could explain, at least partially, the major risk of obesity of formula-fed
      infants with respect to breast-fed infants.

PMID- 16988081
TI  - Dietary quality predicts adult weight gain: findings from the Framingham
      Offspring Study.
AB  - OBJECTIVE: We tested the hypothesis that dietary quality, measured by adherence
      to the Dietary Guidelines, was related to weight change in adults. RESEARCH
      METHODS AND PROCEDURES: Dietary intake was assessed among 2245 adult men and
      women (average age, 49 to 56 years) in the Framingham Offspring cohort. Three-day
      dietary records were collected in 1984 to 1988 and again in 1991 to 1996. Weight
      change was measured over 8 years after each assessment. A five-point diet quality
      index (DQI) was computed based on mean nutrient intake levels from each set of
      diet records. One DQI point was contributed for each of five nutrients if intake
      met Dietary Guidelines for total and saturated fat, cholesterol, sodium, and
      carbohydrate. Gender-specific generalized estimating equations pooled data across
      the two assessments to relate DQI to 8-year weight gain. RESULTS: Men and women
      with higher DQI scores gained less weight during follow-up (p < 0.05). Average
      gain over 8 years was approximately 3 pounds among those with highest scores,
      compared with 5 to 8 pounds among those with lower scores. Smoking cessation was
      an important predictor of weight gain, accounting for about a 5- to 9-pound
      difference in weight gain. DISCUSSION: A high-quality diet, one that is
      consistent with the Dietary Guidelines, may help curb rising rates of obesity at
      the population level. Poor compliance with the Guidelines, rather than the
      guidelines themselves, is likely responsible for the weight gain observed in the
      American population. Adoption of an eating pattern consistent with the Dietary
      Guidelines should facilitate population weight control if sustained long term.

PMID- 16988080
TI  - Effect of weight loss on P wave dispersion in obese subjects.
AB  - OBJECTIVE: The aim of this study was to investigate effect of loss weight on P
      wave dispersion in obese subjects. RESEARCH METHODS AND PROCEDURES: After a 12
      week weight loss program (diet and medical therapy), a total of 30 (24 women and
      six men) obese subjects who had lost at least 10% of their original weight were
      included in the present study. All subjects underwent a routine standard 12-lead
      surface electrocardiogram. Electrocardiograms were transferred to a personal
      computer by a scanner and then magnified 400 times by Adobe Photoshop software
      (Adobe Systems, Mountain View, CA). P wave dispersion, which is also defined as
      the difference between the maximum P wave duration and the minimum P wave
      duration, was also calculated. RESULTS: After a 12-week weight loss program, BMI
      (p < 0.001), maximum P wave duration (p < 0.001), and P wave dispersion (p <
      0.001) significantly decreased. The mean percentage of weight loss was 13% (10%
      to 20.3%). The decrease in the level of P wave dispersion (21 +/- 10 and 7 +/- 12
      ms, p < 0.002) was more prominent in Group II (>or=12% loss of their original
      weight) than Group I (<12% loss of their original weight) after the weight loss
      program. A statistically significant correlation between decrease in the level of
      P wave dispersion and percentage of weight loss was found (r = 0.624, p < 0.001).
      DISCUSSION: Substantial weight loss in obese subjects is associated with a
      decrease of P wave duration and dispersion. Therefore, these observations suggest
      that substantial weight loss is associated with improvement in atrial
      repolarization abnormalities in obese subjects.

PMID- 16988082
TI  - A family-based approach to preventing excessive weight gain.
AB  - OBJECTIVE: Preventing weight gain in adults and excessive weight gain in children
      is a high priority. We evaluated the ability of a family-based program aimed at
      increasing steps and cereal consumption (for breakfast and snacks) to reduce
      weight gain in children and adults. RESEARCH METHODS AND PROCEDURES: Families (n
      = 105) with at least one 8- to 12-year-old child who was at-risk-for-overweight
      or overweight (designated as the target child) were recruited for the study.
      Eighty-two families were randomly assigned to receive the family-based
      intervention and 23 families to the control condition. The 13-week intervention
      consisted of specific increases in daily steps (an additional 2000 steps/d) and
      consumption of 2 servings/d of ready-to-eat cereal. RESULTS: The intervention was
      successful in increasing walking (steps) and cereal consumption. The intervention
      had positive, significant effects on percentage BMI-for-age and percentage body
      fat for target children and weight, BMI, and percentage body fat for parents. On
      further analysis, the positive effects of the intervention were seen largely in
      target girls and moms, rather than in target boys and dads. DISCUSSION: This
      family-based weight gain prevention program based on small changes holds promise
      for reducing excessive weight gain in families and especially in growing
      overweight children.

PMID- 16988083
TI  - Association between obesity and patient satisfaction.
AB  - OBJECTIVE: To examine the relationship between BMI and patient satisfaction with
      health care providers using a nationally representative survey. RESEARCH METHODS
      AND PROCEDURES: This analysis examined the 9914 adult patients who completed the
      2000 Medical Expenditure Panel Survey and had visited a health care provider
      within 12 months of the survey. Linear regression models were employed with
      patient satisfaction as the dependent variable. The patient satisfaction scale
      was based on ratings from five questions assessing the quality of provider
      interactions. The independent variable was BMI, with adjustments for the domains
      of demographics, social-economic status, health attitudes and behavior, health
      status, and health care use. BMI (weight in kilograms/square of height in meters)
      was classified as normal weight (18.5 to 24.9), overweight (25.0 to 29.9), or
      obese (>or=30.0). Hierarchical models were used to evaluate how each domain
      modified the BMI-satisfaction association. RESULTS: Obese patients reported
      significantly greater satisfaction with their health care providers than their
      normal-weight counterparts did (p < 0.05). There were no significant differences
      in satisfaction between normal-weight and overweight patients or between
      overweight and obese patients. The health status domain produced the largest
      modification in the BMI-satisfaction relationship. Examination of interaction
      effects revealed that the association between BMI and satisfaction was confined
      to older persons. DISCUSSION: In this nationally representative sample of
      individuals, obese persons were more satisfied than their normal-weight
      counterparts. This finding counters those of previous studies. Incomplete
      adjustments for health care use and insurance status may have led to those
      conclusions.

PMID- 16988084
TI  - A primary care weight management intervention for low-income African-American
      women.
AB  - OBJECTIVE: To determine whether a tailored weight management program, addressing
      the needs of obese, low-income African-American women, would produce greater
      weight loss than standard medical care. RESEARCH METHODS AND PROCEDURES: A
      randomized, controlled trial was conducted between 1999 and 2003 with 144
      overweight or obese women (predominantly African-American) enrolled at two
      primary care clinics. Four physicians at each clinic were randomly assigned to
      provide either tailored weight management interventions or standard care. The
      tailored condition consisted of six monthly outpatient visits lasting
      approximately 15 minutes each, which included personalized materials and
      messages. The main outcome was body weight change. RESULTS: The intervention
      group lost more weight than the standard care group (p = 0.03). The tailored
      group lost a mean (standard deviation) of 2.0 (3.2) kg by Month 6. The standard
      care group gained 0.2 (2.9) kg. More participants in the tailored group lost
      weight (79% vs. 47%; p = 0.04). DISCUSSION: Obese, low-income, African-American
      women provided with 90 minutes of physician-delivered, tailored weight management
      instruction over 6 months achieved greater weight loss than those receiving
      standard medical care. The primary care physician can be effective in delivering
      weight loss interventions, and the primary care clinic may be a useful setting to
      implement weight management interventions.

PMID- 16988085
TI  - Obesity and attained education: cohort study of more than 700,000 Swedish men.
AB  - OBJECTIVE: To study the relationship between BMI at age 18 years and later
      attained education, with control for intelligence and parental social position.
      RESEARCH METHODS AND PROCEDURES: A cohort of 752,283 Swedish men born from 1952
      to 1973 were followed in registers with respect to attainment of high education
      (>or=15 years of education) until December 31, 2001. Intelligence and BMI
      (kilograms per meter squared) were measured at compulsory military conscription
      at age 18 years. Ninth grade school marks were available for a subgroup born from
      1972 to 1973 (N = 93,374). The hazard ratio for attaining high education was
      estimated with proportional hazard regression analysis controlling for
      intelligence, height, parental socioeconomic position, country of birth,
      conscription center, and municipality. RESULTS: Young men who were obese (BMI
      >or= 30) at age 18 years (N = 10,782) had a much lower chance of attaining a high
      education than normal-weight subjects [(18.5 <or= BMI < 25); adjusted hazard
      ratio 0.48 (95% confidence interval, 0.45, 0.52)]. Young men who were obese at
      age 18 had lower mean ninth grade school marks than young men with normal weight
      at any given intelligence level. DISCUSSION: Obese men in Sweden are doing much
      worse in the educational system than their normal-weight counterparts even after
      adjustments for intelligence and parental socioeconomic position. Discrimination
      in the educational system and other sectors of the society may explain these
      strong associations.

PMID- 16988086
TI  - Construct validity of the Short Form-36 Health Survey and its relationship with
      BMI in obese outpatients.
AB  - OBJECTIVE: To investigate the construct validity of the Short Form-36 (SF-36)
      Health Survey questionnaire in obese patients. RESEARCH METHODS AND PROCEDURES:
      Our series consisted of 1735 obese patients (age, 44.7 +/- 11.0 years; 1346
      women) consecutively enrolled in the QUOVADIS study, an observational multicenter
      study of obese treatment-seeking outpatients. The construct validity of the SF-36
      was assessed by main component analysis. Age-, gender-, and education-adjusted
      general linear models were used to investigate the relationship between BMI and
      SF-36 domains or factors identified by main component analysis. RESULTS: BMI was
      significantly associated with poor health-related quality of life in all eight SF
      36 domains, and the strongest association was observed with physical activity.
      Main components analysis generated a six-factor solution explaining 59% of the
      observed variance. BMI was strongly associated with factors based on the loading
      of items regarding the physical activity domain and factors based on role
      physical and role-emotional items or general health and bodily pain items. In
      contrast, mental health-, vitality-, and social functioning-based factors were
      not related to BMI. DISCUSSION: In obese treatment-seeking outpatients, the
      clustering of SF-36 items in main components is not significantly different from
      the domain-based approach generally used, thus confirming the robustness of such
      a generic questionnaire in this specific condition. However, the peculiar
      clustering of some SF-36 items and their relationship with BMI suggest that the
      health-related quality of life profile of subjects belonging to that population
      may be better described with alternative aggregations of the SF-36 items or with
      disease-tailored questionnaires.

PMID- 16988087
TI  - Freshman 15: fact or fiction?
AB  - OBJECTIVE: The objective of this study was to investigate changes in body weight,
      BMI, body composition, and fat distribution among freshman women during their 1st
      year of college. RESEARCH METHODS AND PROCEDURES: Freshman women during the 2004
      to 2005 academic year were recruited to participate. The initial baseline visit
      occurred within the first 6 weeks of the fall 2004 semester, with the follow-up
      visit occurring during the last 6 weeks of the spring 2005 semester. At each
      visit, height, weight, BMI, waist and hip circumferences, and body composition
      (by DXA) were obtained. RESULTS: One hundred thirty-seven participants completed
      both the fall and spring visits. Significant (p < 0.0001) increases between the
      fall and spring visits were observed for body weight (58.6 vs. 59.6 kg), BMI
      (21.9 vs. 22.3), percentage body fat (28.9 vs. 29.7), total fat mass (16.9 vs.
      17.7 kg), fat-free mass (38.1 vs. 38.4 kg), waist circumference (69.4 vs. 70.3
      cm), and hip circumference (97.4 vs. 98.6 cm), with no significant difference
      observed in the waist-to-hip ratio (0.71 vs. 0.71; p = 0.78). DISCUSSION:
      Although statistically significant, changes in body weight, body composition, and
      fat mass were modest for women during their freshman year of college. These
      results do not support the purported "freshman 15" weight gain publicized in the
      popular media.

PMID- 16988088
TI  - Dietary patterns and changes in body weight in women.
AB  - OBJECTIVE: Our objective was to examine the association between adherence to
      dietary patterns and weight change in women. RESEARCH METHODS AND PROCEDURES:
      Women (51,670, 26 to 46 years old) in the Nurses' Health Study II were followed
      from 1991 to 1999. Dietary intake and body weight were ascertained in 1991, 1995,
      and 1999. A Western pattern, characterized by high intakes of red and processed
      meats, refined grains, sweets and desserts, and potatoes, and a prudent pattern,
      characterized by high intakes of fruits, vegetables, whole grains, fish, poultry,
      and salad dressing, were identified with principal component analysis, and
      associations between patterns and change in body weight were estimated. RESULTS:
      Women who increased their Western pattern score had greater weight gain
      (multivariate adjusted means, 4.55 kg for 1991 to 1995 and 2.86 kg for 1995 to
      1999) than women who decreased their Western pattern score (2.70 and 1.37 kg for
      the two time periods), adjusting for baseline lifestyle and dietary confounders
      and changes in confounders over time (p < 0.001 for both time periods).
      Furthermore, among women who increased their prudent pattern score, weight gain
      was smaller (multivariate-adjusted means, 1.93 kg for 1991 to 1995 and 0.66 kg
      for 1995 to 1999) than among women who decreased their prudent pattern score
      (4.83 and 3.35 kg for the two time periods) (p < 0.001). The largest weight gain
      between 1991 and 1995 and between 1995 and 1999 was observed among women who
      decreased their prudent pattern score while increasing their Western pattern
      score (multivariate adjusted means, 6.80 and 4.99 kg), whereas it was smallest
      for the opposite change in patterns (0.87 and -0.64 kg) (p < 0.001). DISCUSSION:
      Adoption of a Western dietary pattern is associated with larger weight gain in
      women, whereas a prudent dietary pattern may facilitate weight maintenance.

PMID- 16988089
TI  - BMI modifies associations of IL-6 genotypes with insulin resistance: the
      Framingham Study.
AB  - OBJECTIVE: The -174 interleukin (IL)-6 gene polymorphism has been proposed as a
      risk factor for type 2 diabetes, but data are conflicting. Because white fat is a
      major source of IL-6 in resting individuals, we tested the hypothesis that BMI
      modifies the association among the IL-6 genotype, insulin resistance (IR)
      (measured using the homeostasis model), and risk of diabetes. RESEARCH METHODS
      AND PROCEDURES: Outcomes were assessed in a community-based cohort study of 1525
      adults (mean age, 55.6 years; 753 men), who participated in the Framingham
      Offspring Study during the 1991 to 1995 examinations. RESULTS: We found a
      significant interaction between IL-6 genotype and BMI on levels of IR in men (p <
      0.0001), with obese homozygotes for the minor C allele being most resistant. The
      IL-6-BMI interaction was not significant (p = 0.46) in women. Among men with the
      CC genotype, increasing BMI was associated with increased prevalence of diabetes
      [odds ratio (OR) per unit increase in BMI, 1.30; 95% confidence interval (CI),
      1.11 to 1.50] but not among those with the GG (OR, 1.10; 95% CI, 0.98 to 1.22) or
      GC genotype (OR, 1.05; 95% CI, 0.97 to 1.14). DISCUSSION: The -174 IL-6 promoter
      polymorphism modifies the association of obesity with IR and diabetes risk in
      men. Weight loss regimens targeted at reducing the risk of diabetes may be of
      particular benefit for men with a -174 IL-6 CC genotype.

PMID- 16988090
TI  - Prospective associations between sedentary lifestyle and BMI in midlife.
AB  - OBJECTIVE: A strong positive cross-sectional relationship between BMI and a
      sedentary lifestyle has been consistently observed in numerous studies. However,
      it has been questioned whether high BMI is a determinant or a consequence of a
      sedentary lifestyle. RESEARCH METHODS AND PROCEDURES: Using data from four follow
      ups of the University of North Carolina Alumni Heart Study, we examined the
      prospective associations between BMI and sedentary lifestyle in a cohort of 4595
      middle-aged men and women who had responded to questionnaires at the ages of 41
      (standard deviation 2.3), 44 (2.3), 46 (2.0), and 54 (2.0). RESULTS: BMI was
      consistently related to increased risk of becoming sedentary in both men and
      women. The odds ratios of becoming sedentary as predicted by BMI were 1.04 (95%
      confidence limits, 1.00, 1.07) per 1 kg/m(2) from ages 41 to 44, 1.10 (1.07,
      1.14) from ages 44 to 46, and 1.12 (1.08, 1.17) from ages 46 to 54. Controlling
      for concurrent changes in BMI marginally attenuated the effects. Sedentary
      lifestyle did not predict changes in BMI, except when concurrent changes in
      physical activity were taken into account (p < 0.001). The findings were not
      confounded by preceding changes in BMI or physical activity, age, smoking habits,
      or sex. DISCUSSION: Our findings suggest that a high BMI is a determinant of a
      sedentary lifestyle but did not provide unambiguous evidence for an effect of
      sedentary lifestyle on weight gain.

PMID- 16988091
TI  - Midlife obesity and long-term risk of nursing home admission.
AB  - OBJECTIVE: Obesity is a growing problem among middle-aged individuals. We
      investigated whether obesity in middle-aged individuals influences the need for
      future nursing home care and whether the risk of nursing home admission
      associated with obesity is greater in whites than in blacks. RESEARCH METHODS AND
      PROCEDURES: The study population (N = 8804) consisted of long-term members of the
      Kaiser Permanente Medical Care Plan ages 75 to 85 years in 1995 who had completed
      a standardized, multiphasic health checkup while in their 50s. The multiphasic
      health checkup examinations were performed as part of routine medical care
      between the years 1964 and 1973 and included standardized measurements of BMI. We
      used health plan records to assess incident nursing home admissions from 1995 to
      2002. The risk of nursing home admission associated with standard categories of
      midlife BMI was estimated using Cox proportional hazard analysis. RESULTS: During
      an average follow-up of 5.1 years, the nursing home admission rate was 6.8 per
      100 person-years of observation. After adjustment for comorbidities, midlife
      obesity predicted incident nursing home admission approximately 25 years later
      [hazard ratio (HR), 1.30; 95% confidence interval (CI), 1.15 to 1.46; p < 0.001].
      Overweight BMI at midlife was not associated with future nursing home admission
      (HR, 1.05; 95% CI, 0.97 to 1.14; p = 0.23). The risk of nursing home admission
      associated with midlife obesity was higher in whites (HR, 1.34; 95% CI, 1.17 to
      1.54; p < 0.001) than in blacks (HR 1.15; 95% CI, 0.87 to 1.52; p = 0.32), but
      the difference between races was not significant (p for interaction = 0.65).
      DISCUSSION: Obesity among middle-aged individuals is associated with an increased
      risk of nursing home admission in late life and may be an important target for
      reducing the future societal burden of nursing home care.

PMID- 16988092
TI  - Expression of concern - Sudbo J. Novel management of oral cancer: a paradigm of
      predictive oncology. Clin Med Res 2004;2:233-242.

PMID- 16988093
TI  - Carpal tunnel syndrome - adduction versus abduction.

PMID- 16988094
TI  - Dissecting plague.

PMID- 16988095
TI  - Gender, treatment and self-help in remission from alcohol use disorders.
AB  - OBJECTIVES: To examine gender differences in the influence of treatment, self
      help groups and life context and coping factors on remission among initially
      untreated individuals with alcohol use disorders. DESIGN: A naturalistic study in
      which individuals were assessed at baseline and 1, 8 and 16 years later. SETTING:
      Participants initiated help-seeking with the alcoholism service system by
      contacting an information and referral service or detoxification program.
      PARTICIPANTS: A total of 461 individuals with alcohol use disorders (50% women).
      METHODS: Participants were assessed by mail surveys and telephone interviews on
      participation in professional treatment and Alcoholics Anonymous (AA), alcohol
      related functioning and indices of life context and coping. RESULTS: Compared to
      men, women were more likely to participate in treatment and AA, and to experience
      better alcohol-related and life context outcomes. In general, women and men who
      participated in treatment and/or AA for a longer duration were more likely to
      achieve remission. However, women benefited somewhat more than men from extended
      participation in AA. Continuing depression and reliance on avoidance coping were
      more closely associated with lack of remission among men than among women.
      CONCLUSION: Compared to men, women with alcohol use disorders were more likely to
      obtain help and achieve remission. Women tended to benefit more from continued
      participation in AA and showed greater reductions in depression and avoidance
      coping than men did. These findings identify specific targets for clinical
      interventions that appear to be especially beneficial for women and that may also
      enhance the likelihood of recovery among men.

PMID- 16988096
TI  - Submicroscopic Plasmodium falciparum infections before and after sulfadoxine
      pyrimethamine and artesunate association treatment in Dienga, Southeastern Gabon.
AB  - BACKGROUND: It has been shown that Plasmodium falciparum submicroscopic
      infections (SMI) can contribute to malaria-associated anemia as well as to
      cerebral malaria. Polymerase chain reaction (PCR) assays are usually used as an
      alternative to microscopy in detecting subpatently infected individuals.
      OBJECTIVES: The main objective of this study was to investigate the occurrence of
      SMI before and after a suppressive antimalarial treatment in the population of
      the village of Dienga in Gabon. METHODS: Nested PCR was used to detect SMI and to
      determine genotypes. RESULTS: The prevalence rates of SMI were 13.67% (38/278) at
      day 0 and 8.99% (25/278) at day 14 after sulfadoxine-pyrimethamine-artesunate
      treatment. Genotype analysis of two polymorphic regions of the merozoite surface
      protein (MSP)-1 block 2, MSP-2 and a dimorphic region of the erythrocyte binding
      antigen (EBA-175) revealed that as many as 88% (22/25) of SMI detected after
      treatment were completely new alleles, indicating either previously sequestered
      parasites or newly acquired infections. CONCLUSION: These results demonstrate the
      usefulness of sulfadoxine-pyrimethamine-artesunate association treatment in the
      population of Dienga and confirmed early parasite genotype change after a
      suppressive antimalarial treatment in endemic areas.

PMID- 16988097
TI  - The prevalence of growth hormone deficiency and celiac disease in short children.
AB  - OBJECTIVES: To assess the occurrence of growth hormone deficiency (GHD) in
      patients with celiac disease (CD) referred for short stature. DESIGN: A
      retrospective, multi-center study. A total of 7066 children with short stature
      were referred to a number of centers for second-line evaluation over a 5-year
      period. All patients were screened for CD by antiendomysial antibodies (EMA) and
      antitissue transglutaminase IgA. Those with positive sera underwent intestinal
      biopsy. The EMA-negative patients and the EMA-positive ones who did not grow
      after 1 year of gluten-free diet underwent endocrinological investigation.
      RESULTS: Among the 7066 short children (age 2-14 years) evaluated, 650 (9.2%) had
      GHD and 44 (0.63%) had CD. An association of both CD and GHD was found in 16
      short children (0.23%); these children did not grow after 1 year of gluten-free
      diet and therefore GH treatment was started. CONCLUSIONS: GH secretion should be
      evaluated in celiac patients showing no catch-up growth after an appropriate
      period on a gluten-free diet in spite of reversion to seronegativity for EMA.

PMID- 16988098
TI  - Esophageal adenocarcinoma arising from Barrett's dysplasia: a case report of
      double occurrence and prolonged survival after chemotherapy.
AB  - A relatively young patient with chronic gastroesophageal reflux disease (GERD),
      obesity, smoking, and alcohol intake presented with widespread metastatic disease
      in lymph nodes, liver and lungs from a lower esophageal adenocarcinoma extending
      into the gastroesophageal junction associated with Barrett's mucosa and
      dysplasia.A complete response was achieved with six cycles of chemotherapy that
      sustained for more than 4 years without further recurrence. Unfortunately, there
      was presence of esophageal metaplasia after complete response which eventually
      converted to low to high grade dysplasia and ultimately to a second primary
      localized lower esophageal adenocarcinoma that was treated with thoracoabdominal
      esophagectomy and lymphadenectomy. No evidence of disease recurrence was seen 2
      years later. The pathogenesis of a recent increase in the incidence of GERD,
      Barrett's esophagus and lower esophageal adenocarcinoma are discussed. Surgery,
      radiotherapy and combination chemotherapy are effective in the early stages
      leading to tumor shrinkage and prolongation of life and even cure in some cases.
      Lower esophageal adenocarcinoma is frequently associated with Barrett's high
      grade dysplasia. Since there has been a dramatic increase in the incidence of
      Barrett's dysplasia, appropriate surveillance with upper gastrointestinal
      endoscopy and preventive strategies, such as the use of aspirin, cyclo-oxygenase
      II inhibitors and other nonsteroidal antiinflammatory drugs known to be
      chemopreventive agents against colon, esophagus, gastric and bladder cancers,
      need to be studied.

PMID- 16988100
TI  - Postoperative radiotherapy for squamous cell carcinoma of the head and neck.
AB  - This review discusses the role of postoperative radiotherapy (RT) for patients
      with squamous cell carcinoma of the head and neck. Patients with unfavorable
      pathologic features have a high-risk of local-regional recurrence and a decreased
      likelihood of survival after surgery alone. Postoperative RT reduces the risk of
      local-regional failure and probably improves survival. Patients who are at high
      risk for recurrence may benefit from more aggressive altered fractionation
      schedules to decrease the overall time from surgery to the completion of RT.
      Adjuvant cisplatin-based chemotherapy also appears to improve the probability of
      cure in high-risk patients.

PMID- 16988099
TI  - Current trends in plague research: from genomics to virulence.
AB  - Yersinia pestis is the causative agent of plague, which diverged from Yersinia
      pseudotuberculosis within the past 20,000 years. Although these two species share
      a high degree of homology at the DNA level (>90%), they differ radically in their
      pathogenicity and transmission. In this review, we briefly outline the known
      virulence factors that differentiate these two species and emphasize genetic
      studies that have been conducted comparing Y. pestis and Y. pseudotuberculosis.
      These comparisons have led to a better understanding of the genetic contributions
      to the differences in the virulence and pathogenicity between these two organisms
      and have generated information that can be applied in future diagnostic and
      vaccine development. Comparison of the genetic differences between Y. pestis and
      Y. pseudotuberculosis has also lent insight into the emergence of acute pathogens
      from organisms causing milder diseases.

PMID- 16988101
TI  - Universal pathogen-reduced plasma in elective open-heart surgery and liver
      resection.
AB  - ABO-incompatible transfusions and transfusion-related lung injury are today the
      leading transfusion-related causes of death in the developed world. Since anti-A
      and anti-B antibodies in plasma can give rise to serious, even fatal, transfusion
      reactions, ABO-identical/compatible plasma is indicated, but presents a
      logistical challenge and a risk for transfusion of incorrect plasma. In an effort
      to circumvent these problems, an ABO-independent universally applicable, pathogen
      reduced plasma, Uniplas, has been developed and proven safe and efficacious for
      use in adults through prospective, randomized, controlled open-heart surgery
      studies and in prospective, parallel group, controlled liver resection studies.
      The results of these trials are presented and discussed in relation to
      solvent/detergent (SD) treated plasma, in general. The cost effectiveness of
      pathogen-reduced plasma is low because of the very low risk for transfusion
      transmitted viral infections in the developed world (US 2 to 9 million dollars
      per quality-adjusted life year). However, taking into account the combined safety
      of Uniplas with regard to transfusion-related lung injury, pathogen reduction and
      independence of ABO blood groups, the cost per gained life year is reduced to US
      40,000 dollars to 100,000 dollars.

PMID- 16988102
TI  - Gene therapy for cancer treatment: past, present and future.
AB  - The broad field of gene therapy promises a number of innovative treatments that
      are likely to become important in preventing deaths from cancer. In this review,
      we discuss the history, highlights and future of three different gene therapy
      treatment approaches: immunotherapy, oncolytic virotherapy and gene transfer.
      Immunotherapy uses genetically modified cells and viral particles to stimulate
      the immune system to destroy cancer cells. Recent clinical trials of second and
      third generation vaccines have shown encouraging results with a wide range of
      cancers, including lung cancer, pancreatic cancer, prostate cancer and malignant
      melanoma. Oncolytic virotherapy, which uses viral particles that replicate within
      the cancer cell to cause cell death, is an emerging treatment modality that shows
      great promise, particularly with metastatic cancers. Initial phase I trials for
      several vectors have generated excitement over the potential power of this
      technique. Gene transfer is a new treatment modality that introduces new genes
      into a cancerous cell or the surrounding tissue to cause cell death or slow the
      growth of the cancer. This treatment technique is very flexible, and a wide range
      of genes and vectors are being used in clinical trials with successful outcomes.
      As these therapies mature, they may be used alone or in combination with current
      treatments to help make cancer a manageable disease.

PMID- 16988103
TI  - Gastrointestinal stromal tumor with Dieulafoy lesion: a novel association.

PMID- 16988105
TI  - Learning the common language of genetics.

PMID- 16988104
TI  - Megaloblastic anemia and other causes of macrocytosis.

PMID- 16988106
TI  - Sometimes the result is not the answer: the truths and the lies that come from
      using the complementation test.
AB  - It is standard genetic practice to determine whether or not two independently
      obtained mutants define the same or different genes by performing the
      complementation test. While the complementation test is highly effective and
      accurate in most cases, there are a number of instances in which the
      complementation test provides misleading answers, either as a result of the
      failure of two mutations that are located in different genes to complement each
      other or by exhibiting complementation between two mutations that lie within the
      same gene. We are primarily concerned here with those cases in which two
      mutations lie in different genes, but nonetheless fail to complement each other.
      This phenomenon is often referred to as second-site noncomplementation (SSNC).
      The discovery of SSNC led to a large number of screens designed to search for
      genes that encode interacting proteins. However, screens for dominant enhancer
      mutations of semidominant alleles of a given gene have proved far more effective
      at identifying interacting genes whose products interact physically or
      functionally with the initial gene of interest than have SSNC-based screens.

PMID- 16988107
TI  - A sequence-tagged linkage map of Brassica rapa.
AB  - A detailed genetic linkage map of Brassica rapa has been constructed containing
      545 sequence-tagged loci covering 1287 cM, with an average mapping interval of
      2.4 cM. The loci were identified using a combination of 520 RFLP and 25 PCR-based
      markers. RFLP probes were derived from 359 B. rapa EST clones and amplification
      products of 11 B. rapa and 26 Arabidopsis. Including 21 SSR markers provided
      anchors to previously published linkage maps for B. rapa and B. napus and is
      followed as the referenced mapping of R1-R10. The sequence-tagged markers allowed
      interpretation of the pattern of chromosome duplications within the B. rapa
      genome and comparison with Arabidopsis. A total of 62 EST markers showing a
      single RFLP band were mapped through 10 linkage groups, indicating that these can
      be valuable anchoring markers for chromosome-based genome sequencing of B. rapa.
      Other RFLP probes gave rise to 2-5 loci, inferring that B. rapa genome
      duplication is a general phenomenon through 10 chromosomes. The map includes five
      loci of FLC paralogues, which represent the previously reported BrFLC-1, -2, -3,
      and -5 and additionally identified BrFLC3 paralogues derived from local segmental
      duplication on R3.

PMID- 16988109
TI  - Which dietary reference intake is best suited to serve as the basis for nutrition
      labeling for daily values?
AB  - The U.S. Food and Drug Administration is currently reviewing regulations on
      nutrition labeling to better address current health issues as well as updating
      nutrient daily values (DVs), most of which are still based on recommended dietary
      allowances (RDAs) established in 1968. In 2003 the Committee on Use of Dietary
      Reference Intakes in Nutrition Labeling of the Institute of Medicine recommended
      that the DVs be based on the estimated average requirement (EAR) rather than the
      RDA and that a population-weighted mean of EARs be used. The rationale given is
      that the EAR is the best statistical approximation of the nutrient requirement
      for any one individual in the population, and its use would result in a food
      appearing more nutritious, as it would provide a greater percentage of the DV if
      the DV were a smaller amount. Concerns about these recommendations focus on the
      appropriate role of the Nutrition Facts panel, 1 of the 3 major public nutrition
      education tools in the United States (along with MyPyramid and Dietary Guidelines
      for Americans). Providing a benchmark or standard that knowingly has only a 50%
      chance of meeting a consuming individual's requirement is not appropriate. The DV
      on a Nutrition Facts panel should provide useful guidance to the individual about
      how a serving will assist in meeting that person's goal for consumption, and thus
      it should be based on the RDA or adequate intake, rather than the EAR, and be
      derived from the highest recommended intake, as has been the practice since 1973.

PMID- 16988108
TI  - The meiotic bouquet promotes homolog interactions and restricts ectopic
      recombination in Schizosaccharomyces pombe.
AB  - Chromosome architecture undergoes extensive, programmed changes as cells enter
      meiosis. A highly conserved change is the clustering of telomeres at the nuclear
      periphery to form the "bouquet" configuration. In the fission yeast
      Schizosaccharomyces pombe the bouquet and associated nuclear movement facilitate
      initial interactions between homologs. We show that Bqt2, a meiosis-specific
      protein required for bouquet formation, is required for wild-type levels of
      homolog pairing and meiotic allelic recombination. Both gene conversion and
      crossing over are reduced and exhibit negative interference in bqt2Delta mutants,
      reflecting reduced homolog pairing. While both the bouquet and nuclear movement
      promote pairing, only the bouquet restricts ectopic recombination (that between
      dispersed repetitive DNA). We discuss mechanisms by which the bouquet may prevent
      deleterious translocations by restricting ectopic recombination.

PMID- 16988110
TI  - Alignment of the transcription start site coincides with increased
      transcriptional activity from the human asparagine synthetase gene following
      amino acid deprivation of HepG2 cells.
AB  - Transcription initiation sites of the asparagine synthetase gene were
      investigated in human hepatoma cells after amino acid limitation by incubation in
      amino acid-complete minimal essential medium or medium lacking histidine. Cells
      incubated in complete minimal essential medium had mRNA transcripts with starting
      positions spanning across the 69 nucleotides immediately upstream of a previously
      designated transcription start site (+1), whereas the majority of mRNA
      transcripts started at nucleotide (+1) in cells incubated in histidine-free
      medium. Similar results were obtained regardless of whether the analysis was by
      5' rapid amplification of cDNA ends or a ribonuclease protection assay. Low ASNS
      mRNA expression in amino acid-complete medium was associated with the wide range
      of initiation sites, whereas preferred alignment of the general transcription
      machinery at nucleotide (+1), observed in the amino acid deprived condition, was
      associated with a concurrent increase in transcription activity. To our
      knowledge, these results are the first example in a mammalian cell of
      transcription start selection by nutrient availability.

PMID- 16988111
TI  - SREBP1 and thyroid hormone responsive spot 14 (S14) are involved in the
      regulation of bovine mammary lipid synthesis during diet-induced milk fat
      depression and treatment with CLA.
AB  - Milk fat synthesis in dairy cows can be inhibited by unique fatty acid
      intermediates that are produced during rumen biohydrogenation. One of these
      inhibitory intermediates is trans-10, cis-12 conjugated linoleic acid (CLA), and
      this milk fat depression (MFD) involves a coordinated decrease in mammary
      expression of lipogenic enzymes. We investigated the sterol response element
      binding protein (SREBP) transcription factor system in the mammary tissue of cows
      during MFD, which was induced by a low forage, high oil (LF/HO) diet and trans
      10, cis-12 CLA infusion. The LF/HO diet and CLA treatment decreased milk fat
      yield by 38 and 24%, respectively. Treatments causing MFD decreased expression of
      SREBP1 and the insulin responsive gene (INSIG) 1, consistent with decreased
      abundance of active SREBP1. The LF/HO diet also decreased expression of INSIG2
      and SREBP cleavage activating protein. In addition, we identified the involvement
      of thyroid hormone responsive spot 14 (S14) in the regulation of mammary
      synthesis of milk fat. A broader role for S14 in the trans-10, cis-12 CLA
      mediated decrease in fat synthesis was explored by mining publicly available
      microarray datasets, and we found that mouse adipose expression of S14 was
      decreased in response to CLA treatment. Overall, the decreased mammary expression
      of SREBP1, SREBP activation protein, and the coordinated reduction in SREBP1
      responsive lipogenic enzymes provides strong support for a central role of SREBP1
      in the regulation of milk fat synthesis. In addition, our results provide
      evidence for an involvement of S14 in mammary regulation of milk fat synthesis
      and a possible broader role for S14 in the reported antiobesity effects of CLA.

PMID- 16988112
TI  - Glyceroneogenesis is reduced and glucose uptake is increased in adipose tissue
      from cafeteria diet-fed rats independently of tissue sympathetic innervation.
AB  - The pathways of glycerol-3-P (G3P) generation were examined in retroperitoneal
      (RETRO) and epididymal (EPI) adipose tissues from rats fed a cafeteria diet for 3
      wk. The cafeteria diet induced marked increases in body fat mass and in the
      plasma levels of insulin and triacylglycerol (TAG). RETRO and EPI from cafeteria
      diet-fed rats had increased rates of norepinephrine turnover (143 and 60%,
      respectively) and of de novo fatty acid (FA) synthesis (58 and 98%), compared
      with controls fed a balanced commercial diet. Cafeteria diet feeding induced
      marked increases in RETRO and EPI in vivo rates of glucose uptake (52 and 51%,
      respectively), used to evaluate G3P generation via glycolysis, as well as in
      glycerokinase activity (119 and 36%) and TAG-glycerol synthesis from glycerol (56
      and 71%, respectively). In contrast, there was a marked reduction of
      glyceroneogenesis in RETRO and EPI from cafeteria diet-fed rats, which was
      evidenced by the significant decreases of P-enolpyruvate carboxykinase (PEPCK-C)
      activity (48 and 36%) and TAG-glycerol synthesis from pyruvate (45 and 56%,
      respectively). Denervation of RETRO from cafeteria diet-fed rats reduced the
      activity of glycerokinase by 50%, but did not affect glucose uptake or PEPCK-C
      activity and TAG-glycerol synthesis from pyruvate by the tissue. The data show
      that glyceroneogenesis can also be inhibited to adjust the supply of G3P to the
      existing rates of FA esterification and TAG synthesis and suggest that this
      adjustment is made by reciprocal changes in the generation of G3P from glucose
      via glycolysis and from glyceroneogenesis, independently from G3P production by
      glycerokinase.

PMID- 16988113
TI  - Pomegranate juice ellagitannin metabolites are present in human plasma and some
      persist in urine for up to 48 hours.
AB  - Ellagitannins (ETs) from pomegranate juice (PJ) are reported to have numerous
      biological properties, but their absorption and metabolism in humans are poorly
      understood. To investigate the pharmacokinetics of pomegranate ETs, 18 healthy
      volunteers were given 180 mL of PJ concentrate, and blood samples were obtained
      for 6 h afterwards. Twenty-four-hour urine collections were obtained on the day
      before (-1), the day of (0), and the day after (+1) the study. Ellagic acid (EA)
      was detected in plasma of all subjects with a maximum concentration of 0.06 +/-
      0.01 micromol/L, area under concentration time curve of 0.17 +/- 0.02 (micromol x
      h) x L(-1), time of maximum concentration of 0.98 +/- 0.06 h, and elimination
      half-life of 0.71 +/- 0.08 h. EA metabolites, including dimethylellagic acid
      glucuronide (DMEAG) and hydroxy-6H-benzopyran-6-one derivatives (urolithins),
      were also detected in plasma and urine in conjugated and free forms. DMEAG was
      found in the urine obtained from 15 of 18 subjects on d 0, but was not detected
      on d -1 or +1, demonstrating its potential as a biomarker of intake. Urolithin A
      glucuronide was found in urine samples from 11 subjects on d 0 and in the urine
      from 16 subjects on d +1. Urolithin B-glucuronide was found in the urine of 3
      subjects on d 0 and in the urine of 5 subjects on d +1. Urolithins, formed by
      intestinal bacteria, may contribute to the biological effects of PJ as they may
      persist in plasma and tissues and account for some of the health benefits noted
      after chronic PJ consumption. Whether genetic polymorphisms in EA-metabolizing
      enzymes (e.g., catechol-O-methyl transferase and glucuronosyl transferase) are
      related to variations in response to PJ remains to be established.

PMID- 16988114
TI  - Increased luminal mucin does not disturb glucose or ovalbumin absorption in rats
      fed insoluble dietary fiber.
AB  - We tested whether increased mucin secretion due to ingestion of insoluble dietary
      fiber (IDF) affects small intestinal nutrient absorption in rats. Polystyrene
      foam (PSF) with a true expansion ratio of 54.9 was used as a model for IDF with
      high bulk-forming properties. In Expt. 1, rats were fed a control diet or diet
      containing 50 g PSF/kg for 1, 3, 5, or 7 d. Small intestinal mucin fractions were
      isolated, and O-linked oligosaccharide chains were measured. The luminal mucin
      content reached a maximum within 5 d after PSF ingestion. In Expt. 2, rats were
      fed a control diet or diet containing 50 g PSF/kg for 7 d, and then all rats were
      switched to the control diet for 1, 3, or 5 d. The increased capacity for luminal
      mucin secretion disappeared within 5 d after ceasing PSF ingestion. In Expt. 3,
      rats were fed a control diet or diet containing 70 g PSF/kg for 7 d. Glucose
      (1g/kg) was administered orally after 12 h of food deprivation. The blood glucose
      concentrations did not differ between the groups. In Expt. 4, rats were fed a
      control diet or diet containing 90 g PSF/kg for 14 d. At d 7, portal cannulae
      were installed. A mixed solution of glucose (1g/kg) and ovalbumin (OVA, 250
      mg/kg) was orally administered after 12 h of food deprivation, and responses of
      portal glucose and OVA concentrations were monitored for 120 min. Although
      luminal mucin contents were almost doubled in the 9% PSF group compared with the
      control group, neither portal glucose nor OVA concentration differed at any time
      point. The results suggest that the short-term ingestion of IDF significantly
      increases the luminal mucin content, but that this does not disturb nutrient
      absorption.

PMID- 16988115
TI  - A combination therapy including psyllium and plant sterols lowers LDL cholesterol
      by modifying lipoprotein metabolism in hypercholesterolemic individuals.
AB  - We conducted a randomized, double blind, crossover, placebo-controlled study to
      determine the effects of a combination therapy including plant sterols (PS) and
      psyllium (PSY), provided via cookies, on plasma lipids and on the size and
      subfraction distribution of VLDL, LDL, and HDL. Thirty-three healthy free-living
      individuals (11 males and 22 females), aged 35-65 y, with a BMI between 25 and 35
      kg/m(2) and initial plasma LDL cholesterol (LDL-C) concentrations between 2.6 and
      4.1 mmol/L (100 and 160 mg/dL), were randomly assigned to receive treatment
      cookies (7.68 g/d PSY and 2.6 g/d PS) or placebo cookies (0 g PSY+PS) for 4 wk.
      After a 3-wk washout period, subjects received the other cookies for an
      additional 4 wk. Plasma total cholesterol concentrations were significantly
      reduced for all subjects, from 5.65 +/- 0.72 mmol/L after the placebo period to
      5.28 +/- 0.76 mmol/L after the PSY+PS cookie period (P < 0.01). These reductions
      were primarily in LDL-C, which decreased from 3.48 +/- 0.70 to 3.14 +/- 0.78
      mmol/L after PSY+PS cookie consumption (P < 0.01). Intake of the PSY+PS cookie
      decreased the number of intermediate density lipoprotein (IDL), LDL, and HDL
      particles (P < 0.05) and plasma apo B concentrations (P < 0.01). The decreases in
      LDL and HDL particles were in the small subfractions. Because smaller LDL
      particles are associated with an increased risk of heart disease and because
      smaller HDL particles are indicative of diminished reverse cholesterol transport,
      we conclude that the combination therapy resulted in a less atherogenic
      lipoprotein profile. In addition, the evaluation of lipoprotein subfractions
      resulting from the action of the fiber and plant sterols in the intestinal lumen
      provides an insight on the secondary mechanisms of plasma LDL-C lowering.

PMID- 16988116
TI  - Adolescents with adequate birth weight newborns diminish energy expenditure and
      cease growth.
AB  - Maternal energy requirements increase during pregnancy but the magnitude of this
      increment is unknown among adolescents. We determined the effects of maternal age
      and weight status on adjustments in gestational weight gain, resting energy
      expenditure (REE), and growth among adolescents. Weight, and growth rates of
      pregnant adolescents (PA) < or =17 y during late pregnancy were compared with
      changes in nonpregnant adolescents (NPA) over a 5-mo period. REE was also
      measured monthly in the PA group. Paired t-tests and general linear models for
      repeated measures were used for the analysis; height was included as a
      confounding variable. Weight, height, and BMI of the PA and NPA women did not
      differ at baseline. During the follow-up period, NPA grew 0.94 +/- 30 cm; growth
      rate was greater in adolescents < or =14 y of age (P < 0.001) than in the older
      subjects. No growth occurred in the PA group. REE tended to increase linearly
      between 20 and 36 wk of gestation (P = 0.164); the net change in women >14 y
      (25%) tended (P = 0.164) to be greater than that of younger adolescents (7%). The
      mean increment of REE from wk 20 to wk 36 was 230 +/- 30 kcal/d (962 +/- 126
      kJ/d) and the smallest increase occurred in women with BMI <20 (P = 0.010). Women
      with BMI <20 had a decrease in REE/kg that was greater than that of normal weight
      (BMI 20-25) or overweight (BMI > or =25) women (within subject, P = 0.010;
      between subject, P = 0.001). In conclusion, PA appear to adjust their resting
      energy needs by ceasing growth.

PMID- 16988117
TI  - Copper deficiency does not lead to taurine deficiency in rats.
AB  - Copper deficiency has been reported to cause a decrease in urinary taurine
      excretion in rats. We determined whether Cu deficiency would decrease taurine
      status and the hepatic activities of cysteine dioxygenase (CDO) and/or cysteine
      sulfinic acid decarboxylase (CSAD) in rats. Ten weanling male rats were assigned
      to either a Cu-adequate (+Cu) or Cu-deficient (-Cu) group. All rats consumed a Cu
      deficient purified diet and water ad-libitum for 16 wk. The water for the (+Cu)
      group contained 20 mg Cu/L as CuSO(4). At wk 16, the groups differed (P < 0.05)
      in the following variables (means +/- SEM, -Cu vs. +Cu): body weight (BW), 375 +/
      19 vs. 418 +/- 2.9 g; food intake, 16.2 +/- 0.7 vs. 18.5 +/- 0.4 g/d;
      hematocrit, 0.294 +/- 0.027 vs. 0.436 +/- 0.027; hemoglobin, 95.2 +/- 9 vs 134 +/
      10 g/L; liver Cu, 8.7 +/- 2.0 vs. 65.9 +/- 2.5 nmol/g; plasma Cu, 0.38 +/- 0.09
      vs. 13.4 +/- 0.61 micromol/L; plasma ceruloplasmin activity, 1.75 +/- 1.0 vs.
      67.9 +/- 8.4 IU; relative heart weight, 0.56 +/- 0.04 vs. 0.35 +/- 0.02% BW;
      relative liver weight, 4.06 +/- 0.23 vs. 3.37 +/- 0.06% BW; and liver CSAD
      activity, 18.8 +/- 1.37 vs. 13.5 +/- 1.11 nmol x min(-1) x mg protein(-1). The
      groups did not differ at wk 16 in: plasma taurine, 249 +/- 14 vs. 298 +/- 63
      micromol/L; whole blood taurine, 386 +/- 32 vs. 390 +/- 25 micromol/L; urinary
      taurine excretion, 82.5 +/- 15 vs. 52.0 +/- 8.3 micromol/d; liver taurine, 2.6 +/
      0.7 vs. 2.8 +/- 0.4 micromol/g; liver total glutathione, 6.9 +/- 0.48 vs. 6.3 +/
      0.40 micromol/g; liver cyst(e)ine, 96 +/- 7.1 vs. 99 +/- 5.3 nmol/g and liver
      CDO activity, 2.19 +/- 0.33 vs. 2.74 +/- 0.21 nmol x min(-1) x mg protein(-1).
      These findings support the conclusion that Cu deficiency does not affect body
      taurine status.

PMID- 16988118
TI  - The effects of fat and protein on glycemic responses in nondiabetic humans vary
      with waist circumference, fasting plasma insulin, and dietary fiber intake.
AB  - The effects of protein and fat on glycemic responses have not been studied
      systematically. Therefore, our aim was to determine the dose-response effects of
      protein and fat on the glycemic response elicited by 50 g glucose in humans and
      whether subjects' fasting plasma insulin (FPI) and diet influenced the results.
      Nondiabetic humans, 10 with FPI < [corrected] or =40 pmol/L and 10 with FPI >40
      pmol/L, were studied on 18 occasions after 10 14-h overnight fasts. Subjects
      consumed 50 g glucose dissolved in 250 mL water plus 0, 5, 10, or 30 g fat and/or
      0, 5, 10, or 30 g protein. Each level of fat was tested with each level of
      protein. Dietary intake was measured using a 3-d food record. Gram per gram,
      protein reduced glucose responses approximately 2 times more than fat (P < 0.001)
      with no significant fat x protein interaction (P = 0.051). The effect of protein
      on glycemic responses was related to waist circumference (WC) (r = -0.56, P =
      0.011) and intake of dietary fiber (r = -0.60, P = 0.005) but was unrelated to
      FPI or other nutrient intakes. The effect of fat on glycemic responses was
      related to FPI (r = 0.49, P = 0.029) but was unrelated to WC or diet. We conclude
      that, across the range of 0-30 g, protein and fat reduced glycemic responses
      independently from each other in a linear, dose-dependent fashion, with protein
      having approximately 3-times the effect of fat. A large protein effect was
      associated with high WC and high dietary-fiber intake, whereas a large fat effect
      was associated with low FPI. These conclusions may not apply to solid meals.
      Further studies are needed to determine the mechanisms for these effects.

PMID- 16988119
TI  - Epigallocatechin gallate supplementation alleviates diabetes in rodents.
AB  - As the prevalence of type 2 diabetes mellitus is increasing at an alarming rate,
      effective nutritional and exercise strategies for the prevention of this disease
      are required. Specific dietary components with antidiabetic efficacy could be one
      aspect of these strategies. This study investigated the antidiabetic effects of
      the most abundant green tea catechin, epigallocatechin gallate (EGCG, TEAVIGO),
      in rodent models of type 2 diabetes mellitus and H4IIE rat hepatoma cells. We
      assessed glucose and insulin tolerance in db/db mice and ZDF rats after they
      ingested EGCG. Using gene microarray and real-time quantitative RT-PCR we
      investigated the effect of EGCG on gene expression in H4IIE rat hepatoma cells as
      well as in liver and adipose tissue of db/db mice. EGCG improved oral glucose
      tolerance and blood glucose in food-deprived rats in a dose-dependent manner.
      Plasma concentrations of triacylglycerol were reduced and glucose-stimulated
      insulin secretion was enhanced. In H4IIE cells, EGCG downregulated genes involved
      in gluconeogenesis and the synthesis of fatty acids, triacylgycerol, and
      cholesterol. EGCG decreased the mRNA expression of phosphoenolpyruvate
      carboxykinase in H4IIE cells as well as in liver and adipose tissue of db/db
      mice. Glucokinase mRNA expression was upregulated in the liver of db/db mice in a
      dose-dependent manner. This study shows that EGCG beneficially modifies glucose
      and lipid metabolism in H4IIE cells and markedly enhances glucose tolerance in
      diabetic rodents. Dietary supplementation with EGCG could potentially contribute
      to nutritional strategies for the prevention and treatment of type 2 diabetes
      mellitus.

PMID- 16988120
TI  - Consumption of one egg per day increases serum lutein and zeaxanthin
      concentrations in older adults without altering serum lipid and lipoprotein
      cholesterol concentrations.
AB  - Lutein and zeaxanthin accumulate in the macular pigment of the retina, and are
      reported to be associated with a reduced incidence of age-related macular
      degeneration. A rich source of lutein and zeaxanthin in the American diet is the
      yolk of chicken eggs. Thus, the objective of the study was to investigate the
      effect of consuming 1 egg/d for 5 wk on the serum concentrations of lutein,
      zeaxanthin, lipids, and lipoprotein cholesterol in individuals >60 y of age. In a
      randomized cross-over design, 33 men and women participated in the 18-wk study,
      which included one run-in and one washout period of no eggs prior to and between
      two 5-wk interventions of either consuming 1 egg or egg substitute/d. Serum
      lutein 26% (P < 0.001) and zeaxanthin 38% (P < 0.001) concentrations increased
      after 5-wk of 1 egg/d compared with the phase prior to consuming eggs. Serum
      concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, and
      triglycerides were not affected. These findings indicate that in older adults, 5
      wk of consuming 1 egg/d significantly increases serum lutein and zeaxanthin
      concentrations without elevating serum lipids and lipoprotein cholesterol
      concentrations.

PMID- 16988121
TI  - Low plasma taurine concentration in Newfoundland dogs is associated with low
      plasma methionine and cyst(e)ine concentrations and low taurine synthesis.
AB  - Although taurine is not dietarily essential for dogs, taurine deficiency and
      dilated cardiomyopathy (DCM) are sporadically reported in large-breed dogs.
      Taurine status and husbandry were examined in 216 privately owned Newfoundlands,
      a giant dog breed with high incidence of idiopathic DCM (1.3-2.5%). Plasma
      taurine concentration was positively correlated (P < 0.01) with plasma cyst(e)ine
      (r = 0.37) and methionine (r = 0.35) concentrations and was similar across age,
      sex, neutering status, body weight, and body-condition scores. Plasma taurine
      concentration was low (< or =40 micromol/L) in 8% of dogs. Dogs with low plasma
      taurine were older, less active, had more medical problems and treatments, and
      had lower plasma albumin, cyst(e)ine, tryptophan, and alpha-amino-n-butyric acid
      concentrations than the other dogs (P < 0.05). Of 9 taurine-deficient, clinically
      evaluated dogs, 3 had DCM that was reversed by taurine supplementation and 1 had
      retinal degeneration. When given a diet apparently adequate in sulfur amino acids
      (5.4 g/kg) for 3 wk, 6 Newfoundlands (52.5 +/- 2.3 kg, 3.5-7 y), compared with 6
      Beagles (13.2 +/- 2.3 kg, 5.5 y), had lower (P < 0.01) concentrations of plasma
      taurine (49 +/- 16 vs. 97 +/- 25 micromol/L) and cyst(e)ine and blood
      glutathione, lower (P < 0.01) de novo taurine synthesis (59 +/- 15 vs. 124 +/- 27
      mg x kg(-0.75) x d(-1)), and greater (P < 0.05) fecal bile acid excretion (1.7 +/
      0.2 vs. 1.4 +/- 0.2 micromol/g). Newfoundlands would appear to have a higher
      dietary sulfur amino acid requirement than Beagles, a model breed used in
      nutrient requirement determinations.

PMID- 16988122
TI  - Nutritional status is altered in the self-neglecting elderly.
AB  - Elder self-neglect is the most common form of elder mistreatment. Individuals who
      cannot provide basic needs for themselves may develop social, functional, and
      physical deficits. The systematic characterization of self-neglecting individuals
      is the goal of the Consortium for Research in Elder Self-Neglect of Texas
      project. This study reports on the nutritional status of self-neglecting elderly.
      Self-neglectors (SN) were recruited based on referrals along with matched control
      (CN) subjects. Data are for 40 SN subjects (age 76 +/- 7 y) and 40 CN subjects
      (76 +/- 7 y). Blood samples were collected and analyzed for indices of
      nutritional status. SN subjects had a greater serum concentration of total
      homocysteine than CN subjects (13.6 +/- 4.5 vs. 11.6 +/- 5.6 micromol/L, P <
      0.05) and a lower concentration of red blood cell folate (1380 +/- 514 vs. 1792
      +/- 793 nmol/L, P < 0.05). Plasma beta-carotene and alpha-tocopherol were lower
      in SN subjects (0.28 +/- 0.2 vs. 0.43 +/- 0.33 micromol/L; 23.2 +/- 9.3 vs. 27.8
      +/- 9.3 micromol/L, P < 0.05). SN subjects had a lower serum concentration of 25
      hydroxyvitamin D than CN subjects (33.7 +/- 16.4 vs. 44.1 +/- 19.6 nmol/L, P <
      0.05). These differences in markers of nutritional status show that the self
      neglecting elderly are at risk for altered nutritional status, particularly of
      folate, antioxidants, and vitamin D. Evaluation of these data in relation to
      other functional and cognitive assessments are critical for evaluating the
      relation between nutrition and self-neglect.

PMID- 16988123
TI  - Resveratrol is rapidly metabolized in athymic (nu/nu) mice and does not inhibit
      human melanoma xenograft tumor growth.
AB  - Resveratrol has been shown to have anticarcinogenic activity. We previously found
      that resveratrol inhibited growth and induced apoptosis in 2 human melanoma cell
      lines. In this study we determined whether resveratrol would inhibit human
      melanoma xenograft growth. Athymic mice received control diets or diets
      containing 110 micromol/L or 263 micromol/L resveratrol, 2 wk prior to
      subcutaneous injection of the tumor cells. Tumor growth was measured during a 3
      wk period. Metabolism of resveratrol was assayed by bolus gavage of 75 mg/kg
      resveratrol in tumor-bearing and nontumor-bearing mice. Pellets containing 10-100
      mg resveratrol were implanted into the mice, next to newly palpated tumors, and
      tumor growth determined. We also determined the effect of a major resveratrol
      metabolite, piceatannol, on experimental lung metastasis. Resveratrol, at any
      concentration tested, did not have a statistically significant effect on tumor
      growth. The higher levels of resveratrol tested (0.006% in food or 100 mg in slow
      release pellets) tended to stimulate tumor growth (P = 0.08-0.09). Resveratrol
      and its major metabolites, resveratrol glucuronide and piceatannol, were found in
      serum, liver, skin, and tumor tissue. Piceatannol did not affect the in vitro
      growth of a murine melanoma cell line, but significantly stimulated the number of
      lung metastases when these melanoma cells were directly injected into the tail
      vein of the mouse. These results suggest that resveratrol is not likely to be
      useful in the treatment of melanoma and that the effects of phytochemicals on
      cell cultures may not translate to the whole animal system.

PMID- 16988125
TI  - Olive fruit extracts inhibit proliferation and induce apoptosis in HT-29 human
      colon cancer cells.
AB  - Olives and their derivatives represent an important component of the
      Mediterranean diet that has been considered to be protective against cancer. We
      investigated the effect on cell proliferation and apoptosis in HT-29 cells of an
      extract from the skin of olives composed of pentacyclic triterpenes with the main
      components maslinic acid (73.25%) and oleanolic acid (25.75%). Studies of the
      dose-dependent effects showed antiproliferative activity at an EC50 value of
      73.96 +/- 3.19 micromol/L of maslinic acid and 26.56 +/- 2.55 micromol/L of
      oleanolic acid without displaying necrosis. Apoptosis was confirmed by the
      microscopic observation of changes in membrane permeability in 40.9 +/- 3.9% and
      detection of DNA fragmentation in 24.5 +/- 1.5% of HT-29 cells incubated for 24 h
      with olive fruit extract containing 150 and 55.5 micromol/L of maslinic and
      oleanolic acids, respectively. Caspase-3 was activated in a dose-dependent manner
      after incubation for 24 h. The extract containing 200 micromol/L maslinic acid
      and 74 micromol/L oleanolic acid increased caspase-3-like activity to 6-fold that
      of control cells. Programmed cell death was induced by the intrinsic pathway, as
      evidenced by the production of superoxide anions in the mitochondria of cells
      treated with olive fruit extracts containing 150 and 55.5 micromol/L of maslinic
      and oleanolic acids, respectively. Our results report for the first time, to our
      knowledge, the inhibition of cell proliferation without cytotoxicity and the
      restoration of apoptosis in colon cancer cells by maslinic and oleanolic acids
      present in olive fruit extracts.

PMID- 16988124
TI  - Total parenteral nutrition induces liver steatosis and apoptosis in neonatal
      piglets.
AB  - Total parenteral nutrition (TPN) induces a high rate of liver disease in infants,
      yet the pathogenesis remains elusive. We used neonatal piglets as an animal model
      to assess early events leading to TPN-mediated liver injury. Newborn piglets (n =
      7) were nourished for 7 d on TPN or enteral nutrition (EN) and the liver tissue
      and isolated hepatocytes were subjected to morphologic and molecular analysis.
      Histological analysis revealed prominent steatosis (grade > 2) in 6 of 7 TPN
      pigs, whereas minimal steatosis (grade < or = 1) was observed in only 2 EN pigs.
      Abundant cytosolic cytochrome C and DNA fragmentation were observed in
      hepatocytes from TPN compared with EN piglets. Markers of mitochondrial and Fas
      mediated apoptosis were altered in TPN liver tissue, as indicated by a lower ATP
      concentration (P < 0.05), accumulation of ubiquitin, 9.9-fold activation of
      caspase-3 activity (P < 0.01), and increased cleavage of poly-(ADP-ribose)
      polymerase, caspase-8, -9, and -7 when compared with EN livers. Bcl-2 and
      proliferating cell nuclear antigen expression was downregulated, whereas Fas and
      Bax were upregulated in TPN livers. However, levels of caspase-12 and Bip/GRP78,
      both markers of endoplasmic reticulum-mediated apoptosis, did not differ between
      the groups. Short-term TPN induces steatosis and oxidative stress, which results
      in apoptosis mediated by the mitochondrial and Fas pathways. Thus, TPN-induced
      steatosis in newborn piglets may serve as a novel animal model to assess the
      pathogenesis of fatty liver and apoptosis-mediated liver injury in infants.

PMID- 16988126
TI  - Trans fatty acids in human milk in Canada declined with the introduction of trans
      fat food labeling.
AB  - Trans fatty acids in human milk have raised concerns because of possible adverse
      effects on infant growth and development. Analyses of human milk in the late
      1990s in Canada showed high amounts of trans fatty acids from partially
      hydrogenated oils. Canada introduced labeling of trans fatty acids on retail
      foods in 2003. We analyzed trans and cis unsaturated and saturated fatty acids in
      human milk collected from 87 women in 2004-2006 and compared the levels to those
      in milk collected from 103 women in 1998 and analyzed using similar methods. The
      total trans fatty acids (mean +/- SEM, g/100 g fatty acids) in human milk in
      Canada decreased significantly, from 7.1 +/- 0.32 in 1998 to 6.2 +/- 0.48, 5.3 +/
      0.49, and 4.6 +/- 0.32 over 3 consecutive 5-mo periods from November 2004 to
      January 2006. The milk total trans fatty acids were significantly and inversely
      related to 16:0, 18:2(n-6), 18:3(n-3), 20:4(n-6), 22:4(n-6), and 22:5(n-6) and
      positively related to 18:0 and conjugated linolenic acids (P < 0.05, n = 190).
      The estimated exposures of exclusively breast-fed infants to trans fatty acids
      decreased from a mean and 95th percentile intake of 2.0 and 4.4 g x infant(-1) x
      d(-1) in 1998 to 1.33 and 2.41 g x infant(-1) x d(-1), respectively, in late
      2005. The estimated intake of the mothers was 4.0 (range 0.51-12.3) and 2.2 (0.56
      7.65) g x person(-1) x d(-1) in 1998 and late 2005, respectively. Our studies
      show trans fatty acids have decreased in human milk in Canada, which suggests a
      concomitant decrease in trans fatty acid intake among lactating women and breast
      fed infants.

PMID- 16988127
TI  - Carotenoid-biofortified maize maintains adequate vitamin a status in Mongolian
      gerbils.
AB  - Efforts to biofortify maize with provitamin A carotenoids have been successful,
      but the impact on vitamin A (VA) status has not been determined. We conducted two
      studies that investigated the bioefficacy of provitamin A carotenoids from maize
      and compared maize percentage and carotenoid concentrations on VA status in VA
      depleted Mongolian gerbils (Meriones unguiculatus). Gerbils (n = 40/study) were
      fed a white maize diet 4 wk prior to treatment. In study 1, treatments (n =
      10/group) included oil control, 60% high-beta-carotene maize, and beta-carotene
      or VA supplements (matched to high-beta-carotene maize). In study 2, gerbils were
      fed 30 or 60% orange or yellow maize diets. Gerbils were killed after 4 wk. In
      study 1, liver VA concentrations, compared with the high-beta-carotene maize
      group (0.25 +/- 0.15 micromol/g), were higher in the VA group (0.56 +/- 0.15
      micromol/g, P < 0.05), lower in the control (0.10 +/- 0.04 micromol/g, P < 0.05),
      and did not differ in the beta-carotene group (0.25 +/- 0.08 micromol/g).
      Bioconversion was approximately 3 microg beta-carotene to 1 mug retinol (1.5 mol
      beta-carotene to 1 mol retinol). The liver beta-carotene content was greater in
      the high-beta-carotene maize group (26.4 +/- 6.0 nmol) than in the beta-carotene
      supplement group (14.1 +/- 6.0 nmol; P < 0.05). In study 2, the gerbils' VA
      status improved with increasing dietary beta-carotene. Liver VA in gerbils fed
      orange maize was greater than in those fed yellow maize, regardless of maize
      percentage (P < 0.05). Biofortified maize adequately maintained VA status in
      Mongolian gerbils and was as efficacious as beta-carotene supplementation. In
      populations consuming maize as a staple food, using orange instead of white maize
      could dramatically affect VA status.

PMID- 16988128
TI  - A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical
      density in women.
AB  - Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the
      macular retina where they may reduce photostress. Increases in serum lutein and
      zeaxanthin were observed in previous egg interventions, but no study measured
      macular carotenoids. The objective of this project was to determine whether
      increased consumption of eggs would increase retinal lutein and zeaxanthin, or
      macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a
      pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL
      treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments
      consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of
      lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular
      pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of
      intervention. Serum cholesterol concentrations did not change in either egg
      treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02)
      increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in
      both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased
      in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the
      aggregate concentration of carotenoid in 1 egg yolk may be modest relative to
      other sources, such as spinach, their bioavailability to the retina appears to be
      high. Increasing egg consumption to 6 eggs/wk may be an effective method to
      increase MPOD.

PMID- 16988129
TI  - alpha-Tocopherol intake and plasma concentration of Hispanic and non-Hispanic
      white elders is associated with dietary intake pattern.
AB  - alpha-Tocopherol from foods has been associated with protection against several
      chronic diseases and maintenance of immune function. However, most people do not
      meet current recommendations for intake. We examined alpha-tocopherol intake and
      plasma concentration in a representative sample of Puerto Rican and Dominican
      older adults (n = 447) and in neighborhood-matched non-Hispanic whites (n = 155).
      A validated food frequency questionnaire was used to assess dietary intake. Mean
      dietary intakes of alpha-tocopherol were 6 mg in both ethnicities. Only 4.7% of
      women and 7.9% of men met the estimated average requirement (12 mg/d) for vitamin
      E from food alone. Top sources of alpha-tocopherol for Hispanics included oils
      and milk, and for non-Hispanic whites they were ready-to-eat breakfast cereal and
      sweet baked products. Mean plasma alpha-tocopherol concentrations were 24.5
      micromol/L for Hispanics and 25.8 micromol/L for non-Hispanic whites (P > 0.05).
      Plasma alpha-tocopherol was positively associated with alpha-tocopherol intake (P
      = 0.003), and significance remained after adjusting covariates and after
      exclusion of supplement users (P for trend = 0.008). We identified the following
      5 dietary patterns by cluster analysis: 1) fruit and breakfast cereal, 2) starchy
      vegetables, 3) rice, 4) milk and milk products, and 5) sweets. Those following
      the sweets pattern had the lowest plasma alpha-tocopherol relative to those
      following the fruit and breakfast cereal or milk patterns (P < 0.05 for all),
      although they had similar intakes. A large proportion of these elders (>90%) have
      inadequate intake of alpha-tocopherol, and plasma concentrations were associated
      with intake patterns.

PMID- 16988130
TI  - Longitudinal changes in food patterns predict changes in weight and body mass
      index and the effects are greatest in obese women.
AB  - The prevalence of obesity is increasing in most parts of the world. The objective
      of this study was to examine whether changes in food patterns were associated
      with changes in BMI among women over 9 y. Data were from 33,840 women
      participating in the Swedish Mammography Cohort in 1987 and 1997. Diet was
      assessed with a FFQ at both time points and 4 food patterns were derived using
      confirmatory factor analysis (Healthy, Western/Swedish, Alcohol, and Sweets). Our
      exposure variables were defined as change in factor score for each food pattern
      from 1987 to 1997. Our outcome variable was defined as change in BMI during the
      same period, and we also examined change in weight. Normal weight and overweight
      women had positive changes in weight and BMI during follow-up, whereas obese
      women had negative changes in BMI and weight; we observed a significant
      interaction between change in food patterns and baseline BMI. Obese subjects who
      increased their factor score for the Healthy pattern had larger decreases in BMI
      (beta = -0.18 kg/m(2) for a 1 unit increase in SD score, CI: -0.26 to -0.10; P <
      0.0001), whereas normal weight and overweight women who increased their Healthy
      pattern score had smaller increases in BMI (-0.05 kg/m(2) and -0.11 kg/m(2),
      respectively; P < 0.05 for both). Obese women who increased their Healthy pattern
      score >3 SD had almost a 4 kg decrease in weight and a 1 unit decrease in BMI at
      follow-up. In conclusion, changes in eating patterns were significantly related
      to changes in BMI over 9 y and the effect was modified by baseline BMI. Pattern
      analysis is helpful in generating hypotheses regarding the role of diet in
      obesity, and additional research is needed to understand which elements of our
      patterns are protective or risk factors for weight gain.

PMID- 16988131
TI  - Fruit and vegetable consumption and risk of coronary heart disease: a meta
      analysis of cohort studies.
AB  - The consumption of fruit and vegetables is associated with a reduced rate of
      coronary heart disease (CHD) in observational cohorts. The purpose of this study
      was to assess the strength of this association in a meta-analysis. Cohort studies
      were selected if they reported relative risks (RRs) and 95% CI for coronary heart
      disease or mortality and if they presented a quantitative assessment of fruit and
      vegetable intake. The pooled RRs were calculated for each additional portion of
      fruit and/or vegetables consumed per day, and the linearity of the associations
      were examined. Nine studies were eligible for inclusion in the meta-analysis that
      consisted of 91,379 men, 129,701 women, and 5,007 CHD events. The risk of CHD was
      decreased by 4% [RR (95% CI): 0.96 (0.93-0.99), P = 0.0027] for each additional
      portion per day of fruit and vegetable intake and by 7% [0.93 (0.89-0.96), P <
      0.0001] for fruit intake. The association between vegetable intake and CHD risk
      was heterogeneous (P = 0.0043), more marked for cardiovascular mortality [0.74
      (0.75-0.84), P < 0.0001] than for fatal and nonfatal myocardial infarction [0.95
      (0.92-0.99), P = 0.0058]. Visual inspection of the funnel plot suggested a
      publication bias, although not statistically significant. Therefore, the reported
      RRs are probably overestimated. This meta-analysis of cohort studies shows that
      fruit and vegetable consumption is inversely associated with the risk of CHD. The
      causal mechanism of this association, however, remains to be demonstrated.

PMID- 16988132
TI  - The USDA Automated Multiple-Pass Method accurately estimates group total energy
      and nutrient intake.
AB  - The imperative to address the national obesity epidemic has stimulated efforts to
      develop accurate dietary assessment methods suitable for large-scale
      applications. This study evaluated the performance of the USDA Automated Multiple
      Pass Method (AMPM), the computerized dietary recall designed for the National
      Health and Nutrition Examination Survey dietary survey, and 2 epidemiological
      methods [the Block food-frequency questionnaire (Block) and National Cancer
      Institute's Diet History Questionnaire (DHQ)] using doubly labeled water (DLW)
      total energy expenditure (TEE) and 14-d estimated food record (FR) absolute
      nutrient intake as criterion measures. Twenty highly motivated, normal-weight
      stable, premenopausal women participated in a free-living study that included 2
      unannounced AMPM recalls and completion of the Block and DHQ. AMPM and FR total
      energy intake (TEI) did not differ significantly from DLW TEE [AMPM: 8982 +/-
      2625 kJ; FR: 8416 +/- 2217; DLW: 8905 +/- 1881 (mean +/- SD)]. Conversely, the
      questionnaires underestimated TEI by approximately 28% (Block: 6365 +/- 2193;
      DHQ: 6215 +/- 1976; P < 0.0001 vs. DLW). Pearson correlation coefficients for DLW
      TEE with each dietary method TEI showed a stronger linear relation for AMPM (r =
      0.53; P = 0.02) and FR (r = 0.41; P = 0.07) than for the Block (r = 0.25; P =
      0.29) and DHQ (r = 0.15; P = 0.53). Most mean absolute FR nutrient intakes were
      closely approximated by the AMPM but were significantly underestimated by the
      questionnaires. In highly motivated premenopausal women, the AMPM provides valid
      measures of group total energy and nutrient intake whereas the Block and DHQ
      yield underestimations.

PMID- 16988133
TI  - Vitamin A supplementation reduces the monocyte chemoattractant protein-1
      intestinal immune response of Mexican children.
AB  - The impact of vitamin A supplementation on childhood diarrhea may be determined
      by the regulatory effect supplementation has on the mucosal immune response in
      the gut. Previous studies have not addressed the impact of vitamin A
      supplementation on the production of monocyte chemoattractant protein 1 (MCP-1),
      an essential chemokine involved in pathogen-specific mucosal immune response.
      Fecal MCP-1 concentrations, determined by an enzyme-linked immuno absorption
      assay, were compared among 127 Mexican children 5-15 mo of age randomized to
      receive a vitamin A supplement (<12 mo of age, 20,000 IU of retinol; > or =12 mo,
      45,000 iu) every 2 mo or a placebo as part of a larger vitamin A supplementation
      trial. Stools collected during the summer months were screened for MCP-1 and
      gastrointestinal pathogens. Values of MCP-1 were categorized into 3 levels
      (nondetectable, <median, > or =median). Multinomial logistic regression models
      were used to determine whether vitamin A-supplemented children had different
      categorical values of MCP-1 compared with children in the placebo group.
      Differences in categorical values were also analyzed stratified by
      gastrointestinal pathogen infections and by diarrheal symptoms. Overall, children
      who received the vitamin A supplement had reduced fecal concentrations of MCP-1
      compared with children in the placebo group (median pg/mg protein +/-
      interquartile range: 284.88 +/- 885.35 vs. 403.39 +/- 913.16; odds ratio 0.64,
      95% CI 0.42-97, P = 0.03). Vitamin A supplemented children infected with
      enteropathogenic Escherichia coli (EPEC) had reduced MCP-1 levels (odds ratio =
      0.38, 95% CI 0.18-0.80) compared with children in the placebo group. Among
      children not infected with Ascaris lumbricoides vitamin A supplemented children
      had reduced MCP-1 levels (OR = 0.62, 95% CI 0.41-0.94). These findings suggest
      that vitamin A has an anti-inflammatory effect in the gastrointestinal tract by
      reducing MCP-1 concentrations.

PMID- 16988134
TI  - Immunity and antioxidant capacity in humans is enhanced by consumption of a
      dried, encapsulated fruit and vegetable juice concentrate.
AB  - The daily consumption of fruits and vegetables is a common dietary recommendation
      to support good health. We hypothesized that a commercially available
      encapsulated fruit and vegetable juice powder concentrate (FVJC) could support
      functional indices of health due to increased intake of various phytonutrients.
      This was a double-blind, randomized, placebo-controlled investigation of 59
      healthy law students who consumed either FVJC or placebo capsules for 77 d. Blood
      was collected on d 1, 35, and 77 to examine the number of circulating alphabeta-
      and gammadelta-T cells, cytokine production, lymphocyte DNA damage, antioxidant
      status, and levels of carotenoids and vitamin C. A log of illnesses and symptoms
      was also kept. The FVJC group tended to have fewer total symptoms than the
      placebo group (P < 0.076). By d 77 there was a 30% increase in circulating
      gammadelta-T cells and a 40% reduction in DNA damage in lymphocytes in the FVJC
      group relative to the placebo group. Plasma levels of vitamin C and of beta
      carotene, lycopene, and lutein increased significantly from baseline in the FVJC
      group as did plasma oxygen radical absorptive capacity (50%). Interferon-gamma
      produced by phorbol-stimulated lymphocytes was reduced 70% in the FVJC group,
      whereas other cytokines (IL-4, IL-6, transforming growth factor beta) were
      unchanged relative to treatment or time. FVJC consumption during this study
      period resulted in increased plasma nutrients and antioxidant capacity, reduction
      in DNA strand breaks, and an increase in circulating gammadelta-T cells.

PMID- 16988135
TI  - Vitamin C deficiency increases the lung pathology of influenza virus-infected
      gulo-/- mice.
AB  - This study was designed to determine the effects of vitamin C deficiency on the
      immune response to infection with influenza virus. l-Gulono-gamma-lactone oxidase
      gene-inactivated mice (gulo-/- mice) require vitamin C supplementation for
      survival. Five-wk-old male and female gulo-/- mice were provided water or water
      containing 1.67 mmol/L vitamin C for 3 wk before inoculation with influenza
      A/Bangkok/1/79. There were no differences in lung influenza virus titers between
      vitamin C-adequate and -deficient mice; however, lung pathology in the vitamin C
      deficient mice was greater at 1 and 3 d after infection but less at d 7 compared
      with vitamin C-adequate mice. Male vitamin C-deficient mice had higher expression
      of mRNA for regulated upon activation normal T expressed and secreted (RANTES),
      IL-1beta, and TNF-alpha in the lungs at d 1 after infection compared with male
      controls. However, at d 3 after infection, male vitamin C-deficient mice had less
      expression of mRNA for RANTES, monocyte chemotactic protein-1 (MCP-1), and IL-12
      compared with male controls. None of these differences were observed in female
      mice. Vitamin C-deficient male mice also had greater nuclear factor-kappaB
      activation as early as 1 d after infection compared with male controls. These
      data suggest that vitamin C is required for an adequate immune response in
      limiting lung pathology after influenza virus infection.

PMID- 16988136
TI  - Milk folate secretion is not impaired during iron deficiency in humans.
AB  - The purpose of this study was to examine whether maternal iron and/or folate
      status influences human milk folate secretion and is responsible for growth
      faltering of Otomi infants in Capulhuac, Mexico. Breast-feeding mothers (n = 71)
      were randomized at 22 +/- 13 d (baseline) postpartum to receive a daily
      multivitamin supplement containing folic acid (400 microg) with and without iron
      (18 mg). Mothers provided blood and milk samples at baseline, and at 82 +/- 15
      and 138 +/- 18 d postpartum. Iron supplementation significantly improved
      hematocrit and transferrin receptor concentrations but had no influence on
      maternal folate status or milk folate or iron concentrations. Forty-three percent
      of mothers (29/68) had low blood folate concentrations at baseline, whereas only
      6% (4/66) had low blood folate concentrations at approximately 138 d postpartum.
      Milk folate concentrations did not differ between Fe-deficient and Fe-sufficient
      women and provided adequate levels of dietary folate by approximately 82 d
      postpartum. While milk iron concentrations were unrelated to maternal iron
      status, they decreased during lactation, and, by approximately 138 d, they
      provided only 55% of the current recommendation. In conclusion, milk folate
      concentrations appear to be well preserved during maternal iron deficiency;
      hence, faltering growth among infants in Capulhuac, Mexico is unlikely the result
      of reduced milk folate concentration secondary to maternal Fe deficiency.
      However, milk Fe concentrations showed a temporal decline. Whether the
      disjuncture between recommended and actual Fe intakes among infants born with low
      Fe reserves and weaned to foods low in bioavailable Fe has functional
      consequences is worthy of further investigation.

PMID- 16988137
TI  - Dietary diversity scores and nutritional status of women change during the
      seasonal food shortage in rural Burkina Faso.
AB  - In developing countries, dietary diversity is usually assessed during a single
      yearly period and the effects of seasonal variations remain unknown. We studied
      these variations in women living in a Sahelian rural area (Burkina Faso). A
      representative sample of 550 women was surveyed at the beginning and at the end
      of the seasonal cereal shortage in April and September 2003, respectively. For
      each season, a dietary diversity score (DDS) representing the number of food
      groups consumed over a 24-h period, was computed and nutritional status was
      assessed by the BMI. The DDS increased from 3.4 +/- 1.1 to 3.8 +/- 1.5 food
      groups between the beginning and the end of the shortage season (P < 0.0001), and
      the proportion of women exhibiting low DDS decreased from 31.6 to 8.1%. This was
      due to the consumption of foods available during the cereal shortage season and
      despite the decrease in the consumption of some purchased foods. The increase in
      DDS was lower in women for whom DDS was already high in April and vice versa.
      Over the same period, the percentage of underweight women (BMI <18.5 kg/m(2))
      increased from 11.1 to 17.1%. The relation between DDS and the women's
      socioeconomic characteristics or nutritional status was weakened in September.
      Thus, in April, fewer women were underweight when their DDS was high than when it
      was medium or low [odds ratio = 0.3 (0.2; 0.6)], but not in September [odds ratio
      = 0.6 (0.3; 1.0)]. In such a context, it would be useful to measure dietary
      diversity at the beginning of the cereal shortage season, when many women exhibit
      low DDS.

PMID- 16988138
TI  - Fortifying milk with ferrous gluconate and zinc oxide in a public nutrition
      program reduced the prevalence of anemia in toddlers.
AB  - We aimed to assess the efficacy of whole cow's milk fortified with ferrous
      gluconate and zinc oxide, along with ascorbic acid, in reducing the prevalence of
      anemia and improving iron status of low income children 10-30 mo of age. Healthy
      children were randomly assigned to drink 400 mL/d of cow's whole milk, either
      fortified milk (FM) with 5.8 mg/400 mL of iron as ferrous gluconate, 5.28 mg/400
      mL of zinc as zinc oxide, and 48 mg/400 mL of ascorbic acid, or nonfortified milk
      (NFM) with 0.2 mg iron/400 mL, 1.9 mg zinc/400 mL, and 6.8 mg ascorbic acid/400
      mL. Hemoglobin, serum ferritin, soluble transferrin receptors (TfR), and C
      reactive protein concentrations were measured at baseline and 6 mo after
      intervention. The prevalence of anemia declined from 41.4 to 12.1% (P < 0.001),
      or 29 percentage points, in the FM group; there was no change in the NFM group.
      Hemoglobin (coefficient = 0.22, P < 0.01) was positively and TfR (coefficient = 
      0.29, P < 0.001) negatively associated with treatment, controlling for their
      respective baseline values, age, and gender. Treatment with FM was negatively
      associated with the likelihood of being anemic (pseudo R(2) = 0.085, P < 0.03)
      after 6 mo of intervention. Ferrous gluconate added to whole cow's milk as a
      fortificant along with ascorbic acid is efficacious in reducing the prevalence of
      anemia and in improving iron status of Mexican toddlers. The results of this
      study lead to broadening a subsidized FM distribution program to 4.2 million
      beneficiary children 1-11 y of age in Mexico.

PMID- 16988139
TI  - Experiences of Latino immigrant families in North Carolina help explain elevated
      levels of food insecurity and hunger.
AB  - Household food insecurity is higher among minority households in the U.S., but
      few data exist on households of recent minority immigrants, in part because such
      households are difficult to sample. Four studies of a total of 317 Latino
      immigrant families were conducted in different regions and during different
      seasons in North Carolina. A Spanish translation of the 18-item U.S. Food
      Security Survey Module was used to assess the prevalence of food insecurity and
      hunger. In 3 of the studies, a total of 76 in-depth interviews were conducted to
      gather information on immigrants' experiences of food insecurity. Households in
      the 4 studies classified as food secure ranged from 28.7 to 50.9%, compared with
      82.4% in the U.S. in 2004. Food insecurity without hunger ranged from 35.6% to
      41.8%, compared with 13.3% in the U.S. The highest rates of hunger reported were
      18.8% (moderate hunger) and 16.8% (severe hunger) in an urban sample. Qualitative
      data indicate that food insecurity has both quantitative and qualitative effects
      on diet. Immigrants experience adverse psychological effects of food insecurity.
      They report experiencing a period of adjustment to food insecurity leading to
      empowerment to resolve the situation. Reactions to food insecurity differ from
      those reported by others, possibly because immigrants encounter a new and not
      chronic situation. Overall, these findings suggest that immigrant Latinos
      experience significant levels of food insecurity that are not addressed by
      current governmental programs.

PMID- 16988140
TI  - Psychosocial stimulation improves the development of undernourished children in
      rural Bangladesh.
AB  - Undernutrition in early childhood is associated with poor mental development and
      affects 45% of children in Bangladesh. Although limited evidence shows that
      psychosocial stimulation can reduce the deficits, no such interventions have been
      reported from Bangladesh. The Bangladesh Integrated Nutrition Program (BINP) has
      provided nutrition supplementation to undernourished children through community
      nutrition centers (CNCs). We added psychosocial stimulation to the treatment of
      undernourished children in a randomized controlled trial to assess the effects on
      children's development and growth and mothers' knowledge. Twenty CNCs were
      randomly assigned to intervention or control groups with 107 children in each
      group. We also studied 107 nonintervened better-nourished children from the same
      villages. Pre- and postintervention measurements included children's height,
      weight, development assessed on Bayley Scales, behavior ratings during the test,
      and a questionnaire on mothers' knowledge of childrearing. The intervention
      comprised home visits and group meetings with mothers and children for 12 mo.
      Intervention benefited children's mental development (4.6 +/- 2.0, P = 0.02),
      vocalization (0.48 +/- 0.23, P = 0.04), cooperation (0.45 +/- 0.16, P = 0.005),
      response-to-examiner (0.50 +/- 0.15, P = 0.001), emotional tone (0.33 +/- 0.15, P
      = 0.03), and mothers' knowledge (3.5 +/- 0.49, P < 0.001). At the end,
      undernourished controls had poorer mental (-4.6 +/- 2.0, P = 0.02) and motor (
      6.6 +/- 2.2, P = 0.003) development, were more inhibited (-0.35 +/- 0.16, P =
      0.03), fussier (-0.57 +/- 0.16, P < 0.001), less cooperative (-0.48 +/- 0.17, P =
      0.005), and less vocal (-0.76 +/- 0.23, P = 0.001) than better-nourished
      children. Intervened children scored lower only in motor development (-4.4 +/-
      2.3, P = 0.049). Neither group of undernourished children improved in nutritional
      status, indicating that treatment had no effect. In conclusion, adding child
      development activities to the BINP improved children's development and behavior
      and their mothers' knowledge; however, the lack of improvement in growth needs to
      be examined further.

PMID- 16988142
TI  - A research agenda for biomarkers as indicators of cancer risk reduction following
      dietary manipulation.

PMID- 16988141
TI  - A mathematical model gives insights into nutritional and genetic aspects of
      folate-mediated one-carbon metabolism.
AB  - Impaired folate-mediated 1-carbon metabolism has been linked to multiple disease
      outcomes. A better understanding of the nutritional and genetic influences on
      this complex biochemical pathway is needed to comprehend their impact on human
      health. To this end, we created a mathematical model of folate-mediated 1-carbon
      metabolism. The model uses published data on folate enzyme kinetics and
      regulatory mechanisms to simulate the impact of genetic and nutritional variation
      on critical aspects of the pathway. We found that the model predictions match
      experimental data, while providing novel insights into pathway kinetics. Our
      primary observations were as follows: 1) the inverse association between folate
      and homocysteine is strongest at very low folate concentrations, but there is no
      association at high folate concentrations; 2) the DNA methylation reaction rate
      is relatively insensitive to changes in folate pool size; and 3) as folate
      concentrations become very high, enzyme velocities decrease. With regard to
      polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), the modeling
      predicts that decrease MTHFR activity reduces concentrations of S
      adenosylmethionine and 5-methyltetrahydrofolate, as well as DNA methylation,
      while modestly increasing S-adenosylhomocysteine and homocysteine concentrations
      and thymidine or purine synthesis. Decreased folate together with a simulated
      vitamin B-12 deficiency results in decreases in DNA methylation and purine and
      thymidine synthesis. Decreased MTHFR activity superimposed on the B-12 deficiency
      appears to reverse the declines in purine and thymidine synthesis. These
      mathematical simulations of folate-mediated 1-carbon metabolism provide a cost
      efficient approach to in silico experimentation that can complement and help
      guide laboratory studies.

PMID- 16988143
TI  - Research opportunities and needs in the study of dietary modification and cancer
      risk reduction: the role of biomarkers.

PMID- 16988144
TI  - Promises and perils of validating biomarkers for cancer risk.

PMID- 16988145
TI  - Histopathology as a predictive biomarker: strengths and limitations.

PMID- 16988146
TI  - Can indole-3-carbinol-induced changes in cervical intraepithelial neoplasia be
      extrapolated to other food components?

PMID- 16988147
TI  - What do diet-induced alterations in colorectal polyps and aberrant crypts
      indicate for risk?

PMID- 16988148
TI  - Xenobiotic metabolism relevance to cancer.

PMID- 16988149
TI  - What do diet-induced changes in phase I and II enzymes tell us about prevention
      from exposure to heterocyclic amines?

PMID- 16988150
TI  - Dietary factors may modify cancer risk by altering xenobiotic metabolism and many
      other mechanisms.

PMID- 16988151
TI  - Oxidative DNA damage and repair: significance and biomarkers.

PMID- 16988152
TI  - The multifunctional carotenoids: insights into their behavior.

PMID- 16988153
TI  - Oxidative DNA damage and cancer risk assessment.

PMID- 16988154
TI  - Interaction of genetic and dietary factors in mouse intestinal tumorigenesis.

PMID- 16988155
TI  - Differentiation of mammary gland as a mechanism to reduce breast cancer risk.

PMID- 16988156
TI  - What do shifts in indicators of apoptosis indicate about the cancer process?

PMID- 16988157
TI  - PSA: a biomarker for disease. A biomarker for clinical trials. How useful is it?

PMID- 16988158
TI  - Mammographic density: use in risk assessment and as a biomarker in prevention
      trials.

PMID- 16988159
TI  - In the postgenomic era, can high-dimensional analyses deliver the answers we're
      looking for?

PMID- 16988160
TI  - The influence of genetic polymorphism.

PMID- 16988161
TI  - Management of extreme thrombocytosis in otherwise low-risk essential
      thrombocythemia; does number matter?

PMID- 16988162
TI  - Weighing gold or counting spots: which is more sensitive to diagnose latent
      tuberculosis infection?

PMID- 16988163
TI  - Infliximab in sarcoidosis: more answers or more questions?

PMID- 16988164
TI  - Here today--gone tomorrow: the case for transient acute tuberculosis infection.

PMID- 16988165
TI  - Periarterial leukocyte accumulation in allergic airway inflammation.

PMID- 16988166
TI  - Therapeutic options for pulmonary edema associated with nuclear factor-kappaB
      activation in septicemia.

PMID- 16988168
TI  - Effect of extrinsic rearfoot post design on the lateral-to-medial position and
      velocity of the center of pressure.
AB  - Findings from investigations of the effects of external forefoot and rearfoot
      posts added to foot orthoses have been inconclusive. This study was undertaken to
      examine the effects of rearfoot post design on the lateral-to-medial position and
      velocity of the center-of-pressure path. Four identical pairs of neutral-cast
      polypropylene orthotic shells were constructed; three pairs had a rearfoot post
      of specified design added. The fourth pair, the control, did not have a post
      added. Stance period data were broken down into four functional phases, and the
      statistically significant differences between the experimental conditions were
      calculated and analyzed. The addition of a rearfoot post to an orthotic shell
      affects center-of-pressure lateral-to-medial position and velocity. Although the
      effect of the post designs seemed to provide reasonably predictable changes in
      center-of-pressure position, the effect on center-of-pressure velocity was
      variable and inconsistent. The effect of the orthotic post was dependent on
      design and phase of gait. The addition of a rearfoot post and, specifically, the
      design of the post can probably be used to alter the center-of-pressure position
      and velocity.

PMID- 16988169
TI  - Analgesic efficacy of valdecoxib for acute postoperative pain after bunionectomy.
AB  - Two randomized, double-blind, placebo-controlled studies assessed the analgesic
      efficacy of valdecoxib in patients with moderate-to-severe pain after
      bunionectomy. Study 1 (N = 374) assessed the efficacy of two regimens of
      valdecoxib on the day after surgery (valdecoxib, 40 mg, with a 20-mg redose [n =
      127]; valdecoxib, 40 mg, with a placebo redose [n = 122]; and placebo/placebo [n
      = 125]), and study 2 (N = 478) examined the efficacy of two different multiple
      dose regimens on postoperative days 2 through 5 (valdecoxib, 20 mg, twice daily
      [n = 160]; valdecoxib, 20 mg, once daily [n = 159]; and placebo [n = 159]).
      Valdecoxib provided significant pain relief and reduced the use of opioid rescue
      medication. This efficacy was accompanied by improved global scores, decreased
      pain interference with function, and increased patient satisfaction.

PMID- 16988170
TI  - Lower-extremity overuse injury and use of foot orthotic devices in women's
      basketball.
AB  - One hundred thirty-two female basketball players were observed for lower
      extremity overuse injury between 1993 and 2004. Athletes studied between 1993 and
      1996 did not receive foot orthotic devices and composed the control group. The
      treatment group comprised athletes studied between 1996 and 2004. Athletes in the
      treatment group were given a foot orthotic device before participation in
      basketball. Data analysis included lower-extremity overuse injury rates and the
      effect of foot orthotic devices on lower-extremity overuse injury rates by means
      of an incidence density ratio. The control group had a lower-extremity overuse
      injury rate of 5.37 per 1,000 exposures, and the treatment group had a rate of
      6.44 per 1,000 exposures. The incidence density ratio was not significant (P =
      .44). This study rejects the concept that foot orthotic devices may assist in
      prevention of lower-extremity overuse injury in female basketball players.

PMID- 16988171
TI  - Common peroneal nerve compression.
AB  - Entrapment of the common peroneal nerve at the knee can cause sensory and motor
      symptoms and functional problems that affect the foot and ankle. This article
      reviews the signs and symptoms of entrapment of this nerve. It also presents a
      retrospective assessment of subjective improvement in symptoms and the activity
      level after decompression of the common peroneal nerve. A consecutive series of
      17 patients who underwent neurolysis of the common peroneal nerve, 4 bilaterally,
      is reported. Eighteen (86%) of the 21 surgical procedures had a good-to-excellent
      outcome, whereas three outcomes (14%) were not improved. Decompression of the
      common peroneal nerve offers a chance for improvement of sensory and motor
      symptoms in carefully selected patients.

PMID- 16988172
TI  - Sagittal plane range of motion of the pediatric ankle joint: a reliability study.
AB  - Measurement of ankle dorsiflexion is a routine part of the podiatric examination
      of children, yet the reliability of this measure is largely unknown in healthy
      individuals. This study assessed the intrarater and interrater reliability of the
      first and second resistance levels of sagittal ankle range of motion in 4- to 6
      year-old children. The results show that measures of ankle dorsiflexion in
      children are highly variable among examiners, and, in general, gastrocnemius
      range of motion is more reliable than soleal range of motion.

PMID- 16988173
TI  - Comparison of two methods of joint distraction for arthrodesis of the foot.
AB  - A study was conducted to compare the efficacy of two methods of obtaining the
      joint exposure needed to perform arthrodesis or exploration of various joints of
      the foot. The investigation was performed by means of simulated arthrodesis in a
      cadaveric model. On each specimen, a single investigator performed standard
      incisions and dissection as typically performed for surgical arthrodesis of the
      first metatarsocuneiform, naviculocuneiform, medial intercuneiform,
      talonavicular, calcaneocuboid, and subtalar joints. Each joint was exposed and
      distracted once using the Tarsal Joint Distractor (Orthovation LLC, Sealy, Texas)
      and once using the Inge Laminar Spreader (K-Medic, Northvale, New Jersey). While
      a given joint was distracted, a calibrated digital photograph of the exposed
      joint was taken from an angle best representing the surgeon's view of the
      articular space. Digital images were analyzed to calculate the maximum distance
      between articular surfaces and the total area of articular surfaces exposed while
      distracted. Thirty-six joints involving six feet were distracted using each
      device. The mean area of articular exposure was 178.3 mm(2) for the Tarsal Joint
      Distractor and 116.4 mm(2) for the Inge Laminar Spreader (P = .0001). The mean
      distance of distraction was 8.1 mm for the Tarsal Joint Distractor and 6.5 mm for
      the Inge Laminar Spreader (P = .0001). An average of 53.1% more exposure and
      25.2% more distance between distracted surfaces was achieved when using the
      Tarsal Joint Distractor. The Tarsal Joint Distractor provides significantly
      better visualization of articular spaces typical of midfoot and rearfoot
      arthrodesis procedures than the Inge Laminar Spreader.

PMID- 16988174
TI  - Effects of hallux limitus on plantar foot pressure and foot kinematics during
      walking.
AB  - The effects of hallux limitus on plantar foot pressure and foot kinematics have
      received limited attention in the literature. Therefore, a study was conducted to
      assess the effects of limited first metatarsophalangeal joint mobility on plantar
      foot pressure. It was equally important to identify detection criteria based on
      plantar pressures and metatarsophalangeal joint kinematics, enabling
      differentiation between subjects affected by hallux limitus and people with
      normal hallux function. To further our understanding of the relation between
      midtarsal collapse and hallux limitus, kinematic variables relating to midtarsal
      pronation were also included in the study. Two populations of 19 subjects each,
      one with hallux limitus and the other free of functional abnormalities, were
      asked to walk at their preferred speed while plantar foot pressures were recorded
      along with three-dimensional foot kinematics. The presence of hallux limitus,
      structural or functional, caused peak plantar pressure under the hallux to build
      up significantly more and at a faster rate than under the first metatarsal head.
      Additional discriminators for hallux limitus were peak dorsiflexion of the first
      metatarsophalangeal joint, time to this peak value, peak pressure ratios of the
      first metatarsal head and the more lateral metatarsal heads, and time to maximal
      pressure under the fourth and fifth metatarsal heads. Finally, in approximately
      20% of the subjects, with and without hallux limitus, midtarsal pronation
      occurred after heel lift, validating the claim that retrograde midtarsal
      pronation does occur.

PMID- 16988175
TI  - Distribution of the metatarsophalangeal sesamoids in Turkish subjects.
AB  - No statistically significant pattern of metatarsophalangeal sesamoid distribution
      has been reported in the literature in relation to genetic pool or group,
      unilaterality or bilaterality, or sesamoid division. A study was undertaken to
      evaluate the presence and distribution of the metatarsophalangeal sesamoid bones
      of the foot in Turkish subjects. A total of 602 foot radiographs from 371
      patients without forefoot complaints other than those of the hallux were included
      in the study. Absence or hypoplasia of the first-ray sesamoids was seen on 0.7%
      of the radiographs, and second-, third-, fourth-, and fifth-ray sesamoids were
      present on 2.8%, 0.5%, 1.0%, and 15.1% of the radiographs, respectively. Fifth
      ray sesamoids were more prevalent in men (odds ratio, 2.71; 95% confidence
      interval, 1.52-4.84). The frequency of a normal foot profile (two sesamoids in
      the first ray) was 83.2%. Divisions of the sesamoids were seen on 4.0% of the
      radiographs at the first ray and on 20.9% at the fifth ray. Distribution and
      division of sesamoids were predominantly bilateral (kappa = 0.91, 0.91, and 0.95
      for the first, second, and fifth digits, respectively; P < .001).

PMID- 16988176
TI  - Elephantiasis nostras verrucosa.
AB  - Swelling of the leg is a frequent finding in podiatric medicine. Unless the
      patient draws notice to the condition or the physician is diligent in asking
      questions and examining the extremity, the condition may be viewed as minor and
      given little attention. Swelling of the leg can be a clinical sign of certain
      systemic diseases, lymphatic and venous disorders, or other miscellaneous causes.
      Dermatologic consequences linked to many of these causes of swelling are well
      documented. What is not as well chronicled is a dramatic skin alteration
      associated with chronic lymphedema. This article provides an overview and a case
      presentation of the unusual and debilitating skin condition related to chronic
      lymphedema of the lower extremity known as elephantiasis nostras verrucosa.

PMID- 16988177
TI  - Epidermal inclusion cyst in the foot of a Vietnam Veteran.
AB  - Epidermal inclusion cysts are soft-tissue lesions that result from traumatic
      implantation of epidermal cells into the dermis. A case report is presented
      involving a large recurrent plantar inclusion cyst secondary to trauma sustained
      in the Vietnam War. The patient reported that the initiating trauma was the
      result of stepping on a punji stake in Vietnam. Punji stakes, sharpened spikes
      typically made of bamboo and dipped in poison or excrement, were used by the
      Vietnamese soldiers to wound enemy soldiers. Careful excision of the lesion is
      imperative to prevent recurrence.

PMID- 16988178
TI  - A departmental outcome assessment to evaluate educational achievement.
AB  - Defining and addressing outcome objectives is a crucial process in medical
      science and education. One outcome objective of the Physiology/ Pharmacology
      Department at Des Moines University is to prepare students to successfully
      complete Part I of the national licensure examination. This study assesses the
      effectiveness of the departmental curriculum in helping the students achieve
      success on Part I of the licensure examination. Standardized discipline
      examinations were used as the comprehensive final examination for the physiology
      and pharmacology courses for the classes of 1997, 1998, and 2002 through 2005.
      The results were assessed by class year and specific topic area as determined by
      an item keyword description. Student performance on Part I of the National
      Podiatric Board examination was assessed for each class. Podiatric medical
      students' performance tended to be similar to or slightly lower than that of the
      national cohort on the discipline examinations. Topic analysis revealed areas of
      weakness, which were then addressed in the second-year courses. Student
      performance on Part I was generally acceptable yet showed marked improvement with
      the curricular interventions and changes. External assessments provide us with an
      unbiased means to evaluate the strengths and weaknesses of the curriculum through
      student performance and to make appropriate adjustments to enhance students'
      success.

PMID- 16988179
TI  - Complications of a cat bite.

PMID- 16988183
TI  - Effect of early postnatal body weight on femoral head ossification onset and hip
      osteoarthritis in a canine model of developmental dysplasia of the hip.
AB  - Developmental dysplasia of the hip (DDH) is a well-known precipitator of hip
      osteoarthritis. An increase in body weight during the critical early postnatal
      growth period may alter joint contact, and thus alter hip development and
      influence joint health in adulthood. The objective of this study was to determine
      whether early postnatal body weight affected the course of hip development and
      the onset of osteoarthritis in a canine model of DDH. A longitudinal study, from
      birth to skeletal maturity, was conducted. Serial body weight, age at femoral
      head ossification onset, and femoral head coverage at 4 mo were measured.
      Presence and severity of degeneration at 8 mo were determined using necropsy and
      cartilage biochemistry. There was a negative association between birth weight and
      age at femoral head ossification onset; however, the association was likely due
      to skeletal maturity level rather than body weight per se. Lower birth weight
      subjects had greater femoral head coverage at 4 mo. Greater birth weight was
      associated with greater probability of moderate degenerative changes or
      macroscopic lesions at 8 mo. These results support the hypothesis that increased
      birth weight is sufficient to alter the course of hip development and result in
      measurable degenerative changes at adulthood.

PMID- 16988184
TI  - The anti-VEGF antibody bevacizumab potently reduces the growth rate of high-risk
      neuroblastoma xenografts.
AB  - Neuroblastoma (NB) is a rapidly growing, well-vascularized childhood cancer that
      often presents with metastases. The overall five-year survival in NB is
      approximately 45% despite multimodality treatment, and therefore there is a
      clinical need for new therapeutic strategies. NB frequently overexpresses the
      angiogenic factor VEGF (vascular endothelial growth factor). The aim of this
      study was to investigate the effect of bevacizumab (Avastin, Genentech/Roche), a
      humanized anti-VEGF-A antibody, on NB growth in three different xenograft models,
      chosen to resemble high-risk NB. The human NB cell lines SK-N-AS, IMR-32 and SH
      SY5Y, which are poorly differentiated and overexpress VEGF-A, were injected s.c.
      in immunodeficient mice. Bevacizumab was given intraperitoneally twice weekly at
      5 mg/kg body weight, starting at a tumor volume of 0.3 mL. Bevacizumab
      significantly (p < 0.01-0.05) reduced NB growth in vivo without toxicity by
      causing a 30-63% reduction of angiogenesis, but had no effect on NB cell survival
      in vitro. Serum concentrations of VEGF-A increased two- to six-fold during
      bevacizumab therapy which did not result in faster tumor growth compared with
      control animals. Based on our experimental data we suggest consideration of
      bevacizumab in treatment of high-risk NB that does not respond to conventional
      therapy and that overexpresses VEGF.

PMID- 16988185
TI  - Role of ATP-dependent potassium channels in pulmonary vascular tone of fetal
      lambs with congenital diaphragmatic hernia.
AB  - High mortality in newborn babies with congenital diaphragmatic hernia (CDH) is
      principally due to persistent pulmonary hypertension. ATP-dependent potassium
      (K(ATP)) channels might modulate pulmonary vascular tone. We have assessed the
      effects of Pinacidil, a K(ATP) channel opener, and glibenclamide (GLI), a K(ATP)
      channel blocker, in near full-term lambs with and without CDH. In vivo, pulmonary
      hemodynamics were assessed by means of pressure and blood flow catheters. In
      vitro, we used isolated pulmonary vessels and immunohistochemistry to detect the
      presence of K(ATP) channels in pulmonary tissue. In vivo, pinacidil (2 mg)
      significantly reduced pulmonary vascular resistance (PVR) in both controls and
      CDH animals. GLI (30 mg) significantly increased pulmonary arterial pressure
      (PAP) and PVR in control animals only. In vitro, pinacidil (10 microM) relaxed,
      precontracted arteries from lambs with and without CDH. GLI (10(-5) microM) did
      not raise the basal tone of vessels. We conclude that activation of K(ATP)
      channels could be of interest to reduce pulmonary vascular tone in fetal lambs
      with CDH, a condition often associated with persistent pulmonary hypertension of
      the newborn.

PMID- 16988186
TI  - Fingertip force planning during grasp is disrupted by impaired sensorimotor
      integration in children with hemiplegic cerebral palsy.
AB  - In the present study we examine the ability of children with hemiplegic cerebral
      palsy (CP) to use anticipatory control of fingertip forces during grasping, and
      whether anticipatory control is facilitated by lifts with the contralateral hand.
      Eight children with CP (age 4-13) were asked to perform several lifts of either a
      250-g or 500-g object instrumented with force transducers with one hand, followed
      immediately by several lifts with the contralateral hand. This was repeated for
      each combination of weight and starting (involved or non-involved) hand. Similar
      to previous studies, the rate of load force development showed impaired
      anticipatory control during lifts with the involved hand, intact anticipatory
      control in the non-involved hand, and transfer of anticipatory control from the
      non-involved to the involved hand. Surprisingly, however, we also found a
      transfer from the involved hand to the non-involved hand. The results suggest
      that the impaired anticipatory control in the involved hand is not purely a
      sensory or motor problem, and instead is due to an inability to appropriately
      integrate sensory information with subsequent motor output of the same hand.
      These results provide important information about the mechanisms underlying
      impaired anticipatory control, and may have important clinical implications.

PMID- 16988187
TI  - Plasma KL-6 predicts the development and outcome of bronchopulmonary dysplasia.
AB  - Circulating KL-6 is a specific indicator of pulmonary injury affecting the
      alveolar epithelium and interstitium. Our preliminary study suggested the
      usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To
      confirm the diagnostic value of KL-6 for BPD as well as to determine the
      reference range, we conducted a larger prospective study in 135 preterm infants
      <32 wk GA. Among the infants without oxygen dependence at a postconceptional age
      of 36 wk, the plasma KL-6 level showed no significant association with GA at any
      time. Among 42 infants <28 wk GA, plasma KL-6 levels were significantly higher in
      those with moderate/severe BPD compared with those with no/mild BPD. A plasma
      level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of
      moderate/severe BPD <28 wk GA (positive predictive value of 83% and 80%,
      respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6
      objectively reflects the severity of pulmonary injury irrespective of the
      treatment or the radiographic changes. Therefore, not only as a good marker,
      measurement of KL-6 may also help to provide new insights into the pathogenesis
      of BPD.

PMID- 16988188
TI  - Biochemical investigations of bowel inflammation in gastroschisis.
AB  - Neonates with gastroschisis have perivisceritis resulting from contact between
      the bowel and amniotic fluid. Here, we characterized the mediators involved in
      this inflammatory process in humans and ewes, to find a reliable marker of this
      process. We have diagnosed 41 cases of gastroschisis since 1995. Amniotic fluid
      sampled for karyotyping between 15 and 32 wk of gestation was also used to assay
      cytokines and inflammatory proteins. The findings were compared with those in 93
      age-matched controls. Amniotic fluid cells were analyzed by means of cytology.
      Histologic examination of the bowel was performed when neonatal appendectomy was
      performed. The findings were compared with those obtained in a ewe model of
      gastroschisis. In gastroschisis, amniotic total protein, IL-6, IL-8, and ferritin
      levels were significantly higher than in controls. Gastroschisis was associated
      with significantly higher cell counts (mainly mononuclear cells) in amniotic
      fluid. At birth, macrophages were abundant in the fibrous peel covering the
      bowel. Similar results were obtained in the ewe model. Gastroschisis may be
      associated with a subchronic inflammatory process of variable intensity. This
      inflammation is restricted to the bowel wall and involves inflammatory cells such
      as macrophages, which may secrete ferritin, neopterin, and calprotectin.

PMID- 16988189
TI  - Effects of prostacyclin and milrinone on pulmonary hemodynamics in newborn lambs
      with persistent pulmonary hypertension induced by ductal ligation.
AB  - Prostacyclin (PGI(2)) stimulates adenyl cyclase to synthesize cAMP within the
      vascular smooth muscle resulting in vasodilatation. Milrinone inhibits cAMP
      clearance by phosphodiesterase type III. We studied the dose response of
      pulmonary and systemic hemodynamics to intratracheal (IT) PGI(2) in newborn lambs
      with pulmonary hypertension (PH) and whether intravenous milrinone potentiate
      these effects. IT-PGI(2) at varying doses was administered to lambs with PH
      induced by prenatal ductal ligation. IT-PGI(2) doses were repeated in the
      presence of intravenous milrinone (bolus-100 microg/kg followed by infusion at 1
      microg/kg/min). Increasing doses of IT-PGI(2) significantly decreased mean
      pulmonary arterial pressures (PAP) and pulmonary vascular resistance (PVR) and
      increased pulmonary blood flow (PBF). Intravenous milrinone by itself produced a
      significant reduction in PVR and a significant increase in PBF. Intravenous
      milrinone significantly shortened the onset, prolonged the duration and degree of
      pulmonary vasodilation produced by PGI(2). We conclude that intravenous milrinone
      potentiates the pulmonary vasodilator effects of PGI(2) at lower doses.

PMID- 16988190
TI  - Influence of genetic polymorphisms on bone disease of preterm infants.
AB  - Bone disease is an important complication among very low birth weight (VLBW,
      <1500 g) infants. In adults, osteoporosis is associated with polymorphisms of
      vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIA1)
      genes. However, limited information is available regarding the role of these
      polymorphisms in bone disease in premature infants. We have investigated the
      possible association between bone disease and the allelic polymorphisms of these
      three genes in 65 VLBW infants. Twenty infants (30.8%) were diagnosed with bone
      disease based on high activity of bone formation (serum alkaline phosphatase and
      osteocalcin), bone resorption (urinary excretion of calcium and pyridinium
      crosslink) markers, and positive radiologic signs. Statistically significant
      correlation between thymine-adenine repeat [(TA)(n)] allelic variant of ER gene
      and bone disease was observed. Infants without bone disorder more often carried a
      high number of repeats [(TA)(n) >18] [odds ratio (OR): 0.17, 95% confidence
      interval (CI): 0.05-0.55]. A low number of repeats [(TA)(n) <19] was found more
      frequently in infants suffering from bone disease (OR: 6.00, 95% CI: 1.77-20.31).
      Significant interaction (p = 0.009) between VDR and COLIA1 genotypes was
      observed. In a logistic regression model, bone disorder of preterms significantly
      correlated with male gender (p = 0.002), lower gestational age (p = 0.015),
      homozygous allelic variants of high number of (TA)(n) repeats (p = 0.006), and
      interaction between VDR and COLIA1 genotype (p = 0.009).

PMID- 16988191
TI  - American Pediatric Society Presidential Address 2006: science on the edge with
      life in the balance.

PMID- 16988193
TI  - Oxidative stress and antioxidant status in fetal circulation in preeclampsia.
AB  - Preeclampsia is associated with oxidative stress in maternal circulation. The
      purpose of this study was to explore oxidative stress and antioxidants in the
      fetal circulation in preeclampsia. Women with preeclampsia (n = 19) or
      uncomplicated pregnancies (n = 33) delivered by cesarean section were included.
      Blood was sampled separately from the umbilical vein and artery. 8-Iso
      prostaglandin F(2alpha) (8-isoprostane), a stable product of lipid peroxidation,
      is a reliable marker of oxidative stress. Concentration of total 8-isoprostane in
      cord plasma was analyzed by gas chromatography-mass spectrometry. Antioxidant
      status was evaluated measuring ferric reducing ability of plasma and vitamin E.
      There was no difference between preeclampsia and control groups regarding median
      plasma concentration of 8-isoprostane in umbilical vein (955 versus 780 pg/mL, p
      = 0.41) or in umbilical artery (233 versus 276 pg/mL, p = 0.65). Concentration of
      8-isoprostane was much higher in plasma from the umbilical vein than artery,
      suggesting placenta as the source of 8-isoprostane. Median ferric reducing
      ability of plasma concentration was higher in preeclampsia than in controls, both
      in the umbilical vein and artery. Median vitamin E concentration in the umbilical
      vein was higher in preeclampsia, but no difference was found in the umbilical
      artery. In conclusion, no evidence of increased oxidative stress, evaluated by 8
      isoprostane concentration, was found in fetal circulation in preeclampsia.

PMID- 16988192
TI  - IL-6 is constitutively expressed during lung morphogenesis and enhances fetal
      lung explant branching.
AB  - Previous studies have shown that chorioamnionitis, with increased IL-6, promotes
      fetal lung maturation and decreases the incidence of respiratory distress
      syndrome in premature neonates. However, the expression pattern and the effects
      of IL-6 on fetal lung growth mechanisms remain unknown. IL-6 expression was
      assessed by in situ hybridization and by real-time PCR between 14.5 and 21.5 d
      postconception. Normal and nitrofen-induced hypoplastic lung explants were
      cultured with increasing IL-6 doses or IL-6 neutralizing antibodies. Branching,
      cellular proliferation (Ki-67) and MAPK phosphorylation in fetal lung explants
      were analyzed. Pulmonary primitive epithelium expressed IL-6 constitutively
      throughout all gestational ages, displaying highest levels during earliest
      stages. In normal and hypoplastic lung explants, IL-6 neutralizing antibodies
      significantly reduced, whereas IL-6 supplementation induced a biphasic effect
      (lower doses increased, while the highest dose did not accomplish additional
      effect) on branching and cellular proliferation. IL-6 enhanced p38-MAPK
      phosphorylation without changing MEK1/2 and JNK pathways. The present study
      suggests a physiological role for IL-6 on pulmonary branching mechanisms most
      likely involving p38-MAPK intracellular signalling pathway.

PMID- 16988194
TI  - Involvement of TNFalpha -308A promoter polymorphism in the development of asthma
      in children infected with Chlamydophila pneumoniae.
AB  - Several data indicate a connection between Chlamydophila pneumoniae infection and
      asthma. Although C. pneumoniae is a common cause of infection, not all infected
      patients develop asthma. This suggests that certain individuals may be
      genetically predisposed to the chronic effects of C. pneumoniae infection on
      airway functions. We investigated the possible modifying effect of different
      polymorphisms on C. pneumoniae infection and on the susceptibility to asthma in
      318 children, among those 144 had asthma and 174 had no asthmatic symptoms. C.
      pneumoniae-specific antibodies were measured by ELISA. Tumor necrosis factor
      alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and RANTES
      (regulated on activation normal T cell expressed and secreted) genotypes were
      determined by PCR-restriction fragment length polymorphism (RFLP). There were no
      significant differences in the percentage of children positive for C. pneumoniae
      specific antibodies between cases and controls. None of the genotypes was
      associated with altered susceptibility to C. pneumoniae infection. Among
      asthmatic children carrying the TNFalpha -308A allele, there were significantly
      more patients positive for C. pneumoniae-specific IgG, than among control
      children carrying the same allele (20.1% versus 9.2% of asthmatic versus control
      children, respectively; p = 0.002; odds ratio = 3.52 (1.52-7.53); p = 0.005).
      This study indicates the possible roles of polymorphisms in the immune system in
      the susceptibility to asthma in children infected with C. pneumoniae.

PMID- 16988195
TI  - Role of prostanoids in the regulation of cerebral blood flow during normoxia and
      hypoxia in the fetal sheep.
AB  - The fetal cardiovascular responses to hypoxia include decreased peripheral blood
      flow and increased cerebral, cardiac, and adrenal blood flow. Prostanoids,
      metabolites of cyclooxygenase enzyme activity, have potent effects on vascular
      tone in both the adult and the fetus. To examine the role of prostanoids in the
      regulation of fetal cerebral blood flow (CBF) during acute hypoxic stress, eight
      near term fetal sheep were studied after infusing vehicle or diclofenac, a
      cyclooxygenase inhibitor, followed by a 30-min period of hypoxia (arterial Po(2)
      12 Torr). In the control experiments, CBF, measured continuously with laser
      Doppler flowmetry, increased to 148% of baseline values (p < 0.01) and cerebral
      vascular resistance decreased to 70% of baseline values after 30 min of hypoxic
      stress. During diclofenac infusion, hypoxia resulted in a CBF increase to only
      129% of baseline, a significant attenuation (p < 0.05), accompanied by decreased
      plasma prostanoid concentrations. Increases in mean arterial blood pressure
      during hypoxia were also attenuated by diclofenac infusion. Flow and pressure
      responses were not accompanied by changes in cerebral vascular resistance. These
      results indicate that prostanoids indirectly modulate fetal CBF responses to
      hypoxia, but that their effects are mediated through modulation of systemic
      rather than cerebral vascular tone.

PMID- 16988196
TI  - Subcutaneous infusion and capillary "finger stick" sampling of stable isotope
      tracer in metabolic studies.
AB  - Metabolic studies utilizing stable isotope tracer in humans have typically used
      intravenous tracer infusions and venous blood sampling. These studies explore
      subcutaneous infusion of isotope and "finger stick" capillary blood sampling to
      measure glucose turnover. Five subjects received simultaneous 8-h infusions of
      glucose labeled with isotope: [1-(13)C]glucose subcutaneously and [6,6
      (2)H(2)]glucose intravenously. At regular intervals, venous and finger stick
      blood specimens were obtained. Finger stick blood was applied to filter paper.
      Substrate and isotopic steady state was reached after 7.0 h with both routes of
      infusion. The isotopic enrichments of finger stick and venous specimens did not
      differ significantly for the subcutaneously infused [1-(13)C]glucose (p = 0.33
      and p = 0.23, respectively) but the finger stick [6,6-(2)H(2)]glucose enrichment
      was slightly higher (p < 0.03) than that of the venous sample. Using [6,6
      (2)H(2)]glucose infusion and venous plasma sampling as the reference method, the
      [1-(13)C]glucose gave estimates of glucose R(a) that were 13% (plasma) and 17%
      (finger stick) lower (p < 0.001 and p < 0.02, respectively). This difference
      could be attributed to recycling of (13)C label. In conclusion, subcutaneous
      infusion and finger stick specimen collection onto filter paper represent a
      potential method of conducting in vivo studies of substrate metabolism outside of
      a hospital-based research unit.

PMID- 16988197
TI  - Characteristics of arterial stiffness in very low birth weight premature infants.
AB  - Premature birth is a factor of increased blood pressure in adulthood. Little is
      known about the physiologic characteristics of the arterial bed in neonates. The
      aim of this study was to characterize in vivo the arterial compliance in neonates
      and its maturation profile in very low birth weight (VLBW) premature infants. A
      group of stable, VLBW premature infants was compared with a control group of near
      term neonates. The abdominal aortic wall distensibility coefficient (DC) and
      whole-body arterial compliance (WBAC) were determined using specifically designed
      noninvasive methods, based on ultrasonic measurements in combination with
      synchronous, beat-to-beat recording of aortic pulse pressure (PP). On the fifth
      day of life, WBAC and the CD were lower in VLBW premature infants than in
      controls. Furthermore, WBAC and the DC remained unchanged in VLBW premature
      infants 7 wk after birth. In conclusion, VLBW premature infants are characterized
      as early as the fifth day of life by high arterial stiffness, which persists when
      they reach their theoretical term. It can be speculated that early alteration of
      arterial elastic properties may pave the way for long-term elevation of arterial
      pressure in VLBW premature infants.

PMID- 16988199
TI  - Clinical trial design issues: at least 10 things you should look for in clinical
      trials.
AB  - Randomized controlled trials remain the gold standard study design and yield the
      highest level of scientific credence. However, recognition of the limitations of
      the randomized controlled trial is important. This review highlights 10
      potentially problematic areas one should carefully assess when performing or
      reading an article reporting the results of a randomized controlled trial,
      problematic areas that can affect the outcome of the trial and therefore mislead
      the reader. These areas include ethical issues, eligibility criteria, masking
      (blinding), randomization, analytic methods, the selection of subjects for the
      interventional and comparison groups, selection of end points, and the
      interpretation of the results. Each of these is discussed, and examples of
      published articles are used to highlight the main points.

PMID- 16988198
TI  - Amiloride-sensitive nasal potential difference is not changed by estradiol and
      progesterone replacement but relates to BPD or death in a randomized trial on
      preterm infants.
AB  - Postnatal replacement of placental estradiol (E2) and progesterone (P) in preterm
      infants may improve lung function, possibly mediated through enhanced epithelial
      Na(+) transport and alveolar fluid clearance. Preterm infants of <29 wk
      gestational age and <1000 g birth weight requiring mechanical ventilation within
      12 h of birth were randomized to receive either 2.5 mg/kg E2 and 22.5 mg/kg P per
      day (E2/P), or vehicle placebo. Epithelial Na(+) transport was assessed in 29
      infants by measuring total nasal potential difference (NPD) and amiloride
      sensitive NPD (ASNPD) on postnatal days of life 1, 3, 5, and 7, and mean values
      of all four measurements were calculated. Bronchopulmonary dysplasia (BPD) was
      defined as need for supplemental oxygen (goal Sa(O2) 90%) or mechanical
      ventilation at 36 wk corrected postmenstrual age. Mean ASNPD was -6.5 +/- 2.8 mV
      in infants receiving E2/P and -6.1 +/- 2.6 mV in infants receiving placebo (not
      significant). NPD was -10.6 +/- 3.8 mV and -10.7 +/- 3.6 mV, respectively. The
      ASNPD was significantly higher in infants surviving without BPD (-7.1 +/- 2.5 mV)
      than in infants developing BPD or not surviving (-5.2 +/- 2.4 mV). In conclusion,
      ASNPD is not changed by postnatal replacement of E2 and P. Infants at high risk
      of developing BPD had lower ASNPD values in the immediate postnatal period.

PMID- 16988200
TI  - Pharmacokinetics of tipifarnib after oral and intravenous administration in
      subjects with advanced cancer.
AB  - The primary objective of this study was to identify intravenous regimens of
      tipifarnib that would mimic the systemic exposure obtained after the current
      twice-daily oral administration of tipifarnib. After determination of an
      intravenous dose that 6 subjects with advanced cancer could tolerate, another 26
      subjects were randomly assigned to receive 3 consecutive 4-day regimens of
      tipifarnib with different treatment sequences: a 100-mg 2-hour intravenous
      infusion, 200-mg oral administration twice daily, and a 200-mg/d continuous
      intravenous infusion. The systemic exposure to tipifarnib was comparable among
      these 3 regimens. The plasma concentration-time profile of 2-hour intravenous
      infusion more closely resembled the oral administration than did the continuous
      infusion. Glucuronidation is a metabolic pathway for tipifarnib with
      concentrations of the glucuronide conjugate greatly exceeding the parent compound
      after oral and intravenous administration. Analysis of plasma metabolites
      indicated that tipifarnib also undergoes dealkylation and loss of the imidazole
      group.

PMID- 16988201
TI  - Pharmacokinetics of ertapenem in patients with varying degrees of renal
      insufficiency and in patients on hemodialysis.
AB  - Ertapenem is a parenteral beta-lactam carbapenem antibiotic. This open-label
      study examined the pharmacokinetics of single 1-g intravenous doses of ertapenem,
      administered over 30 minutes, in patients with mild, moderate, and advanced renal
      insufficiency (RI) and in patients with end-stage renal disease (ESRD) requiring
      hemodialysis. Pharmacokinetics were compared with historical controls pooled
      across healthy young and elderly subjects. Area under the concentration-time
      curve from time zero to infinity increased 7% in mild, 53% in moderate, 158% in
      advanced RI, and 192% in ESRD; end of infusion concentration changed minimally;
      half-life was 4.5 hours in the historical control group and 4.4, 6.1, 10.6, and
      14.1 hours in mild RI, moderate RI, advanced RI, and ESRD, respectively.
      Hemodialysis cleared approximately 30% of the dose. The recommended dose in mild
      to moderate RI and after hemodialysis is unchanged at 1 g daily; and in advanced
      RI and ESRD is reduced to 0.5 g daily. If the daily dose is given 6 hours prior
      to hemodialysis, a supplementary 150-mg dose (30% of the daily dose) is
      recommended postdialysis.

PMID- 16988202
TI  - Pharmacokinetic evaluation and safety profile of a 15-minute versus 30-second
      infusion of palonosetron in healthy subjects.
AB  - Palonosetron is a potent, selective 5-HT(3) receptor antagonist effective in the
      prevention of acute and delayed chemotherapy-induced nausea and vomiting. In
      practice, 5-HT(3) receptor antagonists, including palonosetron, are often
      coadministered with dexamethasone over approximately 15 minutes, although the
      approval of palonosetron was based on administration as a 30-second infusion.
      This open-label, randomized, 2-way crossover trial compared the pharmacokinetics
      and safety of palonosetron 0.25 mg administered as a 15-minute 50-mL intravenous
      infusion with a 30-second 5-mL infusion. Aside from an anticipated 40% decrease
      in maximum plasma concentration after a 15-minute infusion, the pharmacokinetics
      of palonosetron (including area under the plasma concentration-time curve [AUC],
      plasma elimination half-life, total body clearance, and apparent volume of
      distribution at steady state) were similar for both treatments. Both treatments
      were well tolerated, with no significant changes in vital signs or
      electrocardiograms. Palonosetron infused over 15 minutes is well tolerated, with
      an AUC(0-infinity) equivalent to a 30-second infusion.

PMID- 16988203
TI  - Investigation of a potential food effect on the pharmacokinetics of roflumilast,
      an oral, once-daily phosphodiesterase 4 inhibitor, in healthy subjects.
AB  - This open, randomized, single-dose crossover study investigated effects of a high
      fat meal on the pharmacokinetics of roflumilast and its major active N-oxide
      metabolite. Twelve healthy subjects received oral roflumilast 500 microg (2 x 250
      microg) after overnight fasting and after breakfast. Blood was sampled up to 54
      hours for pharmacokinetic profiling of roflumilast and N-oxide. Geometric mean
      ratios (fed/fasted) for point estimates (PE) and 90% confidence intervals (CI)
      were calculated for AUC(0-last), AUC(0-infinity), and C(max) of both compounds.
      After the meal, roflumilast C(max) (PE, 0.59; 90% CI, 0.49-0.70) was modestly
      reduced; N-oxide C(max) (PE, 0.95; 90% CI, 0.90-1.01) was unchanged. Roflumilast
      t(max) was delayed in fed state (2.0 +/- 0.4 hours) versus fasted state (1.0 +/-
      0.2 hours); N-oxide t(max) was unaltered. No significant food effect on
      roflumilast AUC(0-last) (PE, 1.04; 90% CI, 0.90-1.21), AUC(0-infinity) (PE, 1.12;
      90% CI, 1.00-1.25), and respective N-oxide AUCs (PE, 0.91; 90% CI, 0.79-1.04; PE,
      0.99; 90% CI, 0.92-1.06) occurred. Because roflumilast N-oxide is the major
      contributor to roflumilast's overall pharmacologic effects, these findings
      suggest that roflumilast can be taken with or without food.

PMID- 16988204
TI  - Gatifloxacin pharmacokinetics in healthy men and women.
AB  - The sex-based pharmacokinetics of gatifloxacin were investigated. Healthy
      subjects (6 men, 6 women) received a single oral dose of gatifloxacin 400 mg.
      Blood and urine samples were collected, and gatifloxacin concentrations were
      determined by high-performance liquid chromatography. Pharmacokinetic parameters
      were estimated by fitting appropriate models to the serum concentration-time data
      using ADAPT II. Linear regression analysis was used to determine the influence of
      sex and weight on the oral clearance (CL(s)/F) and apparent steady-state volume
      of distribution (V(ss)/F) of gatifloxacin. Women had a significantly smaller
      V(ss)/F compared to men (93.5 +/- 21.3 L vs 128.8 +/- 16.2 L, P = .009); however,
      there was no significant difference when normalized for total body weight (TBW)
      or lean body weight (LBW). Neither CL(s)/F nor peak serum concentration (C(max))
      was significantly different between sexes, although C(max) was 25% higher in
      women (P = .06). Regression analyses revealed that TBW (R(2) = .63) and LBW (R(2)
      = .65) were strong predictors of V(ss)/F. Given the smaller V(ss)/F, women may
      have slightly higher maximum concentrations, but these differences are unlikely
      to have clinical significance.

PMID- 16988205
TI  - Disposition and metabolite kinetics of oral L-carnitine in humans.
AB  - The pharmacokinetics of L-carnitine and its metabolites were investigated in 7
      healthy subjects following the oral administration of 0, 0.5, 1, and 2 g 3 times
      a day for 7 days. Mean plasma concentrations of L-carnitine across an 8-hour dose
      interval increased significantly (P < .05) from a baseline of 54.2 +/- 9.3 microM
      to 80.5 +/- 12.5 microM following the 0.5-g dose; there was no further increase
      at higher doses. There was a significant increase (P < .001) in the renal
      clearance of L-carnitine indicating saturation of tubular reabsorption.
      Trimethylamine plasma levels increased proportionately with L-carnitine dose, but
      there was no change in renal clearance. A significant increase in the plasma
      concentrations of trimethylamine-N-oxide from baseline was evident only for the 2
      g dose of L-carnitine (from 34.5 +/- 2.0 to 149 +/- 145 microM), and its renal
      clearance decreased with increasing dose (P < .05). There was no evidence for
      nonlinearity in the metabolism of trimethylamine to trimethylamine-N-oxide. In
      conclusion, the pharmacokinetics of oral L-carnitine display nonlinearity above a
      dose of 0.5 g 3 times a day.

PMID- 16988206
TI  - Population pharmacokinetic analysis and dosing regimen optimization of meropenem
      in adult patients.
AB  - The objectives of this study were to develop a meropenem population
      pharmacokinetic model using patient data and use it to explore alternative dosage
      regimens that could optimize the currently used dosing regimen to achieve higher
      likelihood of pharmacodynamic exposure against pathogenic bacteria. We gathered
      concentration data from 79 patients (ages 18-93 years) who received meropenem
      0.5, 1, or 2 g over 0.5- or 3-hour infusion every 8 hours. Meropenem population
      pharmacokinetic analysis was performed using the NONMEM program. A 2-compartment
      model fit the data best. Creatinine clearance, age, and body weight were the most
      significant covariates to affect meropenem pharmacokinetics. Monte Carlo
      simulation was applied to mimic the concentration-time profiles while 1 g
      meropenem was administrated via infusion over 0.5, 1, 2, and 3 hours. The 3-hour
      prolonged infusion improved the likelihood of obtaining both bacteriostatic and
      bactericidal exposures most notably at the current susceptibility breakpoints.

PMID- 16988207
TI  - Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in
      healthy Asian men.
AB  - Exenatide, a treatment for type 2 diabetes, slows gastric emptying as part of its
      pharmacologic action and may alter the absorption of concomitant oral drugs. This
      open-label, 2-period, fixed-sequence study evaluated the influence of exenatide
      coadministration on the pharmacokinetics and pharmacodynamics of warfarin, a
      narrow therapeutic index drug, in healthy men (N = 16). A single, 25-mg oral dose
      of warfarin, with a standardized breakfast, was administered alone in period 1
      and concomitantly with 10 microg exenatide subcutaneous twice daily in period 2.
      Exenatide did not produce significant changes in R- or S-warfarin
      pharmacokinetics. Although there were minor reductions in warfarin anticoagulant
      effect, the ratios of geometric means for the area under the international
      normalized ratio (INR)-time curve from dosing until the time of the last
      measurable INR value or maximum-observed INR response being 0.94 (0.93-0.96) and
      0.88 (0.84-0.92), respectively, the magnitude and direction of these changes do
      not suggest a safety concern from this interaction.

PMID- 16988208
TI  - Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy
      volunteers: an open-label, pharmacokinetic interaction clinical trial.
AB  - The effects of the CYP3A4 inducer, Hypericum perforatum, on the pharmacokinetics
      of a single oral dose of ivabradine were assessed. An open-label, 2-period,
      nonrandomized, phase-I, pharmacokinetic interaction design was used. Twelve
      healthy volunteers received a single oral dose of ivabradine (10 mg) followed by
      H perforatum (300 mg orally, 3 times a day) for 14 days, combining the last dose
      with another single dose of ivabradine. Pharmacokinetic data for ivabradine
      (S16257) and its main active metabolite (S18982) prior to and after the
      administration of H perforatum were analyzed. After repeated administration of H
      perforatum, highest observed concentration in plasma (C(max)) and area under the
      concentration-time curve (AUC) were significantly decreased for ivabradine (32.7
      +/- 16.6 vs 15.4 +/- 7.0 ng/mL, P < .01; 114 +/- 39.1 vs 43.7 +/- 12.0 ng x h/mL,
      P < .01, respectively), and for S18982 (C(max), 6.8 +/- 3.7 vs 5.1 +/- 2.0 ng/mL,
      P < .05; AUC, 56.2 +/- 23.4 vs 38.3 +/- 25.1 ng x h/mL, P < .01). Tendencies
      toward shorter time to C(max) and lower apparent terminal half-life values were
      found. Pharmacokinetic results are consistent with an induction of ivabradine
      metabolism by H perforatum.

PMID- 16988209
TI  - Lack of pharmacokinetic interaction between omeprazole or lansoprazole and
      ivabradine in healthy volunteers: an open-label, randomized, crossover,
      pharmacokinetic interaction clinical trial.
AB  - The effects of omeprazole and lansoprazole (CYP3A4 inhibitors) on the
      pharmacokinetics of a single dose of ivabradine (metabolized via CYP3A4) and its
      active metabolite (S18982) were assessed. Pharmacodynamics and safety were
      secondary objectives. An open-label, randomized, crossover, phase I,
      pharmacokinetic interaction design was used. Volunteers received a single oral
      dose of ivabradine (10 mg), were randomized to receive either omeprazole (40 mg)
      or lansoprazole (60 mg) for 5 days, and were administered an ivabradine dose on
      the sixth day. Crossover was performed after washout. Pharmacokinetic parameters
      for ivabradine did not vary significantly after omeprazole (C(max): 45.0 +/- 36.6
      vs 42.7 +/- 27.6 ng/mL, P = .98; AUC: 128 +/- 87 vs 126 +/- 63 ng/mL, P = .82) or
      lansoprazole administration (C(max): 45.0 +/- 36.6 vs 41.3 +/- 29.4 ng/mL, P =
      .70; AUC: 128 +/- 87 vs 123 +/- 50, P = .73). Analyses of S18982 pharmacokinetic
      parameters showed similar results. Coadministration of either omeprazole or
      lansoprazole did not significantly affect the pharmacokinetics of a single dose
      of ivabradine. No pharmacodynamic interaction or safety concerns were evidenced.

PMID- 16988210
TI  - Pharmacokinetics of desmopressin administrated as an oral lyophilisate dosage
      form in children with primary nocturnal enuresis and healthy adults.
AB  - The population pharmacokinetics of desmopressin in children with nocturnal
      enuresis and in healthy adults were compared using a 1-compartment model with
      first-order absorption and first-order elimination. In addition, the model
      consisted of a number of transit compartments before absorption to describe a lag
      time. The model gave an adequate description of adult as well as children data
      and provided a statistically significant better fit to data than a standard lag
      time model. The main difference in the pharmacokinetics between children and
      adults was the absorption delay. The pharmacokinetic difference was minor and
      presumably of no clinical relevance.

PMID- 16988211
TI  - Effect of food on the bioavailability of amlodipine besylate/atorvastatin calcium
      combination tablet.

PMID- 16988212
TI  - A pharmacokinetic comparison of generic tablets containing bisoprolol with the
      innovator formulation in healthy volunteers.

PMID- 16988213
TI  - Functional HY-specific CD8+ T cells are found in a high proportion of women
      following pregnancy with a male fetus.
AB  - Recent studies have demonstrated that fetal cells can be detected in the maternal
      circulation during virtually all human pregnancies. These fetal cells can engraft
      and may be isolated for many decades after pregnancy, leading to a state that may
      be maintained by the passage of pregnancy-associated progenitor cells. The
      clinical consequences of fetal cell microchimerism are unclear but may be
      potentially detrimental or valuable to the mother. One possibility is the
      generation of an alloreactive immune response by the mother to antigens expressed
      by the fetus; for example, the HY protein encoded by the Y chromosome. To test
      this we have screened a cohort of women with a range of parity histories within 8
      yr of their last pregnancy for the presence of an HY-specific CD8+ T-cell
      response. Fluorescent HLA-peptide (HY) tetramers were used to stain short-term T
      cell cultures from these women for analysis by flow cytometry. Responses were
      detected in 37% of women with a history of pregnancies that produced males, and
      this value rose to 50% in women with two or more pregnancies that produced males.
      HY-specific CD8+ T cells also could be detected directly in the peripheral blood
      of women with a history of at least two pregnancies that produced males. These HY
      specific CD8+ T cells produced interferon gamma (IFNG) following peptide
      stimulation, demonstrating their functional capacity. In conclusion, our data
      indicate that alloreactive CD8+ T cells are generated frequently following normal
      pregnancy and retain functional capability for years following pregnancy.

PMID- 16988214
TI  - Regulation of cavernous nerve injury-induced apoptosis by sonic hedgehog.
AB  - Thirty to eighty-seven percent of patients treated by radical prostatectomy
      experience erectile dysfunction (ED). The reduced efficacy of treatments in this
      population makes novel therapeutic approaches to treat ED essential. We propose
      that abundant apoptosis observed in penile smooth muscle when the cavernous nerve
      (CN) is cut (mimicking the neural injury which can result from prostatectomy) is
      a major contributing factor to ED development. We hypothesize that decreased
      Sonic hedgehog (SHH) signaling is a cause of ED in neurological models of
      impotence by increasing apoptosis in penile smooth muscle. We examined this
      hypothesis in a bilateral CN injury model of ED. We found that the active form of
      SHH protein was significantly decreased 1.2-fold following CN injury, that SHH
      inhibition causes a 12-fold increase in smooth muscle apoptosis in the penis, and
      that SHH treatment at the time of CN injury was able to decrease CN injury
      induced apoptosis (1-3-fold) in a dose-dependent manner. These results show that
      SHH stabilizes the alterations of the corpora cavernosal smooth muscle following
      nerve injury.

PMID- 16988215
TI  - Differential expression of genes encoding constitutive and inducible 20S
      proteasomal core subunits in the testis and epididymis of theophylline- or 1,3
      dinitrobenzene-exposed rats.
AB  - Theophylline (THP) and 1,3-dinitrobenzene (DNB) are thought to induce infertility
      by incapacitating the nurturing Sertoli cells and causing germ cell apoptosis in
      the testicular seminiferous epithelium, respectively. We hypothesized that THP
      and DNB exposure would alter the expression of the genes within the ubiquitin
      proteasome pathway (UPP), implicated in spermatogenesis and epididymal sperm
      quality control. Rats were fed 0 or 8000 ppm of THP and necropsied on Days 18,
      30, and 42 or administered 0, 2, or 6 mg/kg DNB via oral gavage and necropsied on
      Day 7. Tissues were collected from the testis and the caput, corpus, and cauda
      regions of the epididymis for transcriptional profiling by semiquantitative RT
      PCR, real-time RT-PCR, and histopathology. Target UPP genes included those
      encoding for constitutive the 20S proteasomal core subunits Psmb1 (beta1), Psmb2
      (beta2), and Psmb5 (beta5); the inducible 20S core subunits Psmb9 (LMP2), Psmb8
      (LMP7), and Psmb10 (LMP10); and Ube1 (ubiquitin-activating enzyme E1), Ube2d3
      (ubiquitin-conjugating enzyme E2), and Uchl1 (ubiquitin C-terminal hydrolase
      PGP9.5). Spermatozoa were collected from the cauda epididymis for analysis by
      light microscopy and flow cytometric evaluation of sperm surface ubiquitin. These
      data show that reprotoxic exposure alters the tissue-specific expression of UPP
      genes in the testis and epididymis, which may contribute to the aberrant
      spermatogenesis and epididymal processing of both normal and defective
      spermatozoa. Transcriptional profiling and flow cytometric analysis of the UPP
      thus captures the prodromal effects of reproductive toxicity not captured by
      conventional histology and functional cytology. Complementing seminal analysis
      with these measures may be useful in screening drug-induced toxicity or
      environmental infertility.

PMID- 16988217
TI  - Intestinal microvascular endothelium and innate immunity in inflammatory bowel
      disease: a second line of defense?

PMID- 16988218
TI  - Major role for FeoB in Campylobacter jejuni ferrous iron acquisition, gut
      colonization, and intracellular survival.
AB  - To assess the importance of ferrous iron acquisition in Campylobacter physiology
      and pathogenesis, we disrupted and characterized the Fe2+ iron transporter, FeoB,
      in Campylobacter jejuni NCTC 11168, 81-176, and ATCC 43431. The feoB mutant was
      significantly affected in its ability to transport 55Fe2+. It accumulated half
      the amount of iron than the wild-type strain during growth in an iron-containing
      medium. The intracellular iron of the feoB mutant was localized in the
      periplasmic space versus the cytoplasm for the wild-type strain. These results
      indicate that the feoB gene of C. jejuni encodes a functional ferrous iron
      transport system. Reverse transcriptase PCR analysis revealed the cotranscription
      of feoB and Cj1397, which encodes a homolog of Escherichia coli feoA. C. jejuni
      81-176 feoB mutants exhibited reduced ability to persist in human INT-407
      embryonic intestinal cells and porcine IPEC-1 small intestinal epithelial cells
      compared to the wild type. C. jejuni NCTC 11168 feoB mutant was outcompeted by
      the wild type for colonization and/or survival in the rabbit ileal loop. The feoB
      mutants of the three C. jejuni strains were significantly affected in their
      ability to colonize the chick cecum. And finally, the three feoB mutants were
      outcompeted by their respective wild-type strains for infection of the intestinal
      tracts of colostrum-deprived piglets. Taken together, these results demonstrate
      that FeoB-mediated ferrous iron acquisition contributes significantly to
      colonization of the gastrointestinal tract during both commensal and infectious
      relationship, and thus it plays an important role in Campylobacter pathogenesis.

PMID- 16988219
TI  - Autoinducer 3 and epinephrine signaling in the kinetics of locus of enterocyte
      effacement gene expression in enterohemorrhagic Escherichia coli.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is responsible for causing
      outbreaks of bloody diarrhea and hemolytic-uremic syndrome throughout the world.
      The locus of enterocyte effacement (LEE) consists of five major operons and is
      required for the formation of attaching and effacing lesions that disrupt
      intestinal epithelial microvilli. We have previously reported that expression of
      EHEC LEE genes is regulated by the luxS quorum-sensing system. The luxS gene in
      EHEC affects the production of autoinducer 3 (AI-3), which activates the LEE.
      Epinephrine and norepinephrine also activate the LEE in a manner similar to that
      of AI-3. Previous studies of quorum-sensing regulation of LEE transcription have
      thus far been restricted to using reporter systems in an E. coli K-12 background.
      Here, we examined the kinetics of LEE gene transcription, protein expression, and
      function of the LEE type III secretion apparatus in wild-type (WT) EHEC and an
      isogenic luxS mutant. The results revealed that the luxS mutant had diminished
      transcription from the LEE promoters during the mid-exponential growth phase;
      decreased protein levels of EscJ, Tir, and EspA; and reduced secretion of EspA
      and EspB. The luxS mutation also caused a delay in the formation of attaching and
      effacing lesions on cultured epithelial cells compared to the wild type.
      Epinephrine enhanced LEE expression in both the WT and the luxS mutant, but the
      WT still exhibited greater LEE activation. The results suggest a possible
      synergistic relationship between AI-3 and epinephrine. The combined effects of
      these two signaling molecules may lead to greater LEE expression and a more
      efficient infection.

PMID- 16988220
TI  - Extensive genotypic diversity in a recombining population of the apicomplexan
      parasite Theileria parva.
AB  - We evaluated sexual recombination in the apicomplexan parasite Theileria parva
      using genome-wide marker analysis of haploid sporozoite populations obtained from
      infected Rhipicephalus appendiculatus ticks. Analysis of 231 parasite clones
      derived by in vitro infection of bovine lymphocytes revealed 48 distinct
      combinations of 64 polymorphic marker loci. One genotype accounted for more than
      75% of the clones, and the population was highly inbred with respect to this. The
      occurrence of frequent recombination was evident from reassortment of contiguous
      markers in blocks, with some recombination occurring within blocks. Analysis of
      four polymorphic loci encoding antigens targeted by protective cytotoxic-T
      lymphocyte responses confirmed that these loci reassort, both within and between
      chromosomes, suggesting that recombination may influence immune recognition.
      Marker analysis of a panel of 142 clones derived from the population after an
      additional passage through a calf and the same tick colony revealed 18 genotypes,
      with the original dominant genotype accounting for 75% of the population and a
      higher level of inbreeding with respect to it in the remaining clones. Selected
      marker analysis of genomic DNA from these stabilates and the two preceding
      generations of the isolate, each derived from distinct tick colonies, revealed
      shifts in population structure with each generation, suggesting that the tick
      vector may impose nonrandom selective pressure on the parasite.

PMID- 16988221
TI  - Genome-wide expression analysis of Burkholderia pseudomallei infection in a
      hamster model of acute melioidosis.
AB  - Burkholderia pseudomallei is the causative agent of melioidosis and represents a
      potential bioterrorism threat. In the current studies we have examined gene
      expression in B. pseudomallei in an animal model of acute melioidosis using whole
      genome microarrays. Gene expression profiles were generated by comparing
      transcriptional levels of B. pseudomallei-expressed genes in infected hamster
      organs including liver, lung, and spleen following intraperitoneal and intranasal
      routes of infection to those from bacteria grown in vitro. Differentially
      expressed genes were similar in infected livers irrespective of the route of
      infection. Reduced expression of a number of housekeeping genes suggested a lower
      bacterial growth rate during infection. Energy production during growth in vivo
      involved specific biochemical pathways such as isomerization of 3
      phosphoglycerate, catabolism of d-glucosamine and inositol, and biosynthesis of
      particular amino acids. In addition, the induction of genes known to be involved
      in oxidative phosphorylation including ubiquinol oxidase, ferredoxin
      oxidoreductase, and formate dehydrogenase enzymes suggested the use of
      alternative pathways for energy production, while the expression of genes coding
      for ATP-synthase and NADH-dehydrogenase enzymes was reduced. Our studies have
      identified differentially expressed genes which include potential virulence genes
      such as those for a putative phospholipase C and a putative two-component
      regulatory system, and they have also provided a better understanding of
      bacterial metabolism in response to the host environment during acute
      melioidosis.

PMID- 16988222
TI  - The mgtC gene of Burkholderia cenocepacia is required for growth under magnesium
      limitation conditions and intracellular survival in macrophages.
AB  - Burkholderia cenocepacia, a bacterium commonly found in the environment, is an
      important opportunistic pathogen in patients with cystic fibrosis (CF). Very
      little is known about the mechanisms by which B. cenocepacia causes disease, but
      chronic infection of the airways in CF patients may be associated, at least in
      part, with the ability of this bacterium to survive within epithelial cells and
      macrophages. Survival in macrophages occurs in a membrane-bound compartment that
      is distinct from the lysosome, suggesting that B. cenocepacia prevents
      phagolysosomal fusion. In a previous study, we employed signature-tagged
      mutagenesis and an agar bead model of chronic pulmonary infection in rats to
      identify B. cenocepacia genes that are required for bacterial survival in vivo.
      One of the most significantly attenuated mutants had an insertion in the mgtC
      gene. Here, we show that mgtC is also needed for growth of B. cenocepacia in
      magnesium-depleted medium and for bacterial survival within murine macrophages.
      Using fluorescence microscopy, we demonstrated that B. cenocepacia mgtC mutants,
      unlike the parental isolate, colocalize with the fluorescent acidotropic probe
      LysoTracker Red. At 4 h postinfection, mgtC mutants expressing monomeric red
      fluorescent protein cannot retain this protein within the bacterial cytoplasm.
      Together, these results demonstrate that, unlike the parental strain, an mgtC
      mutant does not induce a delay in phagolysosomal fusion and the bacterium
      containing vacuoles are rapidly targeted to the lysosome, where bacteria are
      destroyed.

PMID- 16988223
TI  - Fatty acids from Plasmodium falciparum down-regulate the toxic activity of
      malaria glycosylphosphatidylinositols.
AB  - Plasmodium falciparum malaria kills roughly 2.5 million people, mainly children,
      annually. Much of this mortality is thought to arise from the actions of a
      malarial toxin. This toxin, identified as glycosylphosphatidylinositol (GPI), is
      a major pathogenicity determinant in malaria. A malarial molecule, Pfj, labeled
      by [3H]glucosamine like the GPIs, was identified as a non-GPI molecule. Here we
      show that Pfj is able to down-regulate tumor necrosis factor alpha (TNF-alpha)
      production induced by the GPI of P. falciparum. Mass spectrometry analysis showed
      that Pfj was not a single molecule but represented a number of molecules.
      Separation methods, such as cation-exchange chromatography and thin-layer
      chromatography, were used to isolate and identify the following four main fatty
      acids responsible for the inhibitory effect on TNF-alpha production: myristic,
      pentadecanoic, palmitic, and palmitoleic acids. This regulatory effect on
      cytokine production suggests that there is balanced bioactivity for the different
      categories of malarial lipids.

PMID- 16988224
TI  - Neutrophils do not mediate the pathophysiological sequelae of Cryptosporidium
      parvum infection in neonatal piglets.
AB  - Cryptosporidium parvum is a minimally invasive protozoal pathogen of intestinal
      epithelium that results in villus atrophy, mucosal lipid peroxidation, diarrhea,
      and diminished barrier function. Influx of neutrophils is a consistent feature of
      human and animal cryptosporidiosis, and yet their contribution to the
      pathological sequelae of infection has not been investigated. Accordingly, we
      used an established neonatal piglet model of C. parvum infection to examine the
      role of neutrophils in disease pathogenesis by inhibiting their recruitment and
      activation in vivo using a monoclonal anti-CD18 antibody. Infected piglets were
      treated daily with anti-CD18 or isotype control immunoglobulin G and euthanized
      at peak infection, at which time neutrophil infiltrates, lipid peroxidation,
      severity of infection, and intestinal barrier function were quantified. C. parvum
      infection resulted in a significant increase in mucosal neutrophil
      myeloperoxidase activity that was prevented by treatment of piglets with anti
      CD18 antibody. Neutrophil recruitment was dependent on mucosal superoxide
      formation (prevented by treatment of infected piglets with superoxide dismutase).
      Neutrophils did not contribute to peroxynitrite formation or peroxidative injury
      of C. parvum-infected mucosa and had no impact on the severity of epithelial
      infection, villus atrophy, or diarrhea. The presence of neutrophils in C. parvum
      infected mucosa was associated with enhanced barrier function that could not be
      attributed to mucosal elaboration of prostaglandins or stimulation of their
      synthesis. These studies are the first to demonstrate that neutrophilic
      inflammation arising in response to infection by a noninvasive epithelial
      pathogen results in physiologic rather than pathological effects in vivo.

PMID- 16988225
TI  - Differential role of lipooligosaccharide of Neisseria meningitidis in virulence
      and inflammatory response during respiratory infection in mice.
AB  - Meningococcal lipooligosaccharide (LOS) induces a strong proinflammatory response
      in humans during meningococcal infection. We analyzed the role of LOS in the
      inflammatory response and virulence during the early infectious process in a
      mouse model of meningococcal respiratory challenge. An lpxA mutant strain
      (serogroup B) devoid of LOS (strain Z0204) could not persist in the lungs and did
      not invade the blood. The persistence in the lungs and invasion of the
      bloodstream by a rfaD mutant expressing truncated LOS with only lipid A and 3
      deoxy-d-manno-2-octulosonic acid molecules (strain Z0401) was intermediate
      between those of the wild-type and Z0204 strains. Both LOS mutants induced acute
      pneumonia with the presence of infiltrating polymorphonuclear leukocytes in
      lungs. Although tumor necrosis factor alpha production was reduced in mice
      infected with the mutant of devoid LOS, both LOS mutants induced production of
      other proinflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6, and
      the murine IL-8 homolog KC. Together, these results suggest that meningococcal
      LOS plays a role during the early infectious and invasive process, and they
      further confirm that other, nonlipopolysaccharide components of Neisseria
      meningitidis may significantly contribute to the inflammatory reaction of the
      host.

PMID- 16988226
TI  - Inhibition of matrix metalloproteinases protects mice from ascending infection
      and chronic disease manifestations resulting from urogenital Chlamydia muridarum
      infection.
AB  - Matrix metalloproteinases (MMP) are a family of host-derived enzymes involved in
      the turnover of extracellular matrix molecules. We have previously reported
      enhanced expression of matrix metalloproteinases in Chlamydia muridarum
      urogenital tract infection of female mice. Kinetics and patterns of MMP
      expression as well as enhanced expression in susceptible strains of mice in the
      prior study implied a role for MMP in pathogenesis. To explore this further, we
      infected a susceptible strain of mice (C3H/HeN) with C. muridarum and treated two
      groups of mice with either one of two chemical inhibitors of MMP (MMPi; captopril
      and a chemically modified tetracycline) and reserved infected sham-treated mice
      as controls. Neither of the treatments affected shedding of viable chlamydiae
      from the lower urogenital tract, but the administration of either MMPi protected
      mice from the formation of hydrosalpinx-a surrogate marker of oviduct occlusion
      and infertility. Interestingly, the mechanism of protection for mice treated with
      chemically modified tetracycline 3, appeared to be related to prevention of
      ascending upper genital tract infection. These results imply that MMP are
      involved in pathogenesis of chlamydial infection in this model by mediating
      ascension of the infection into the upper genital tract.

PMID- 16988227
TI  - Actin cytoskeleton-dependent and -independent host cell invasion by Trypanosoma
      cruzi is mediated by distinct parasite surface molecules.
AB  - The disassembly of host cell actin cytoskeleton as a facilitator of Trypanosoma
      cruzi invasion has been reported by some authors, while other workers claim that
      it instead inhibits internalization of the parasite. In this study we aimed at
      elucidating the basis of this discrepancy. We performed experiments with
      metacyclic trypomastigotes of T. cruzi strains G and CL, which differ markedly in
      infectivity and enter target cells by engaging the surface molecules gp35/50 and
      gp82, respectively, which have signaling activity. Treatment of HeLa cells with
      the F-actin-disrupting drug cytochalasin D or latrunculin B inhibited the
      invasion by strain G but not the invasion by strain CL. In contrast to cells
      penetrated by strain CL, which were previously shown to have a disrupted actin
      cytoskeleton architecture, no such alteration was observed in HeLa cells invaded
      by strain G, and parasites were found to be closely associated with target cell
      actin. Coinfection with enteroinvasive Escherichia coli (EIEC), which recruits
      host cell actin for internalization, drastically reduced entry of strain CL into
      HeLa cells but not entry of strain G. In contrast to gp82 in its recombinant
      form, which induces disruption of F-actin and inhibits EIEC invasion, purified
      mucin-like gp35/50 molecules promoted an increase in EIEC uptake by HeLa cells.
      These data, plus the finding that drugs that interfere with mammalian cell
      signaling differentially affect the internalization of metacyclic forms of
      strains G and CL, indicate that the host cell invasion mediated by gp35/50 is
      associated with signaling events that favor actin recruitment, in contrast to
      gp82-dependent invasion, which triggers the signaling pathways leading to
      disassembly of F-actin.

PMID- 16988228
TI  - Passive immunization with a multicomponent vaccine against conserved domains of
      apical membrane antigen 1 and 235-kilodalton rhoptry proteins protects mice
      against Plasmodium yoelii blood-stage challenge infection.
AB  - During malaria parasite invasion of red blood cells, merozoite proteins bind
      receptors on the surface of the erythrocyte. Two candidate Plasmodium yoelii
      adhesion proteins are apical membrane antigen 1 (AMA1) and the 235-kDa rhoptry
      proteins (P235). Previously, we have demonstrated that passive immunization with
      monoclonal antibodies (MAbs) 45B1 and 25.77 against AMA1 and P235, respectively,
      protects against a lethal challenge infection with P. yoelii YM. We show that MAb
      45B1 recognizes an epitope located on a conserved surface of PyAMA1, as
      determined by phage display and analysis of the three-dimensional structure of
      AMA1, in a region similar to that bound by the P. falciparum AMA1-specific
      inhibitory antibody 4G2. The epitope recognized by 25.77 could not be assigned.
      We report here that MAbs 45B1 and 25.77 also protect against challenge with the
      nonlethal parasite line 17X, in which PyAMA1 has a significantly different amino
      acid sequence from that in YM. When administered together, the two MAbs acted at
      least additively in providing protection against challenge with the virulent YM
      parasite. These results support the concept of developing a multicomponent blood
      stage vaccine and the inclusion of polymorphic targets such as AMA1, which these
      results suggest contain conserved domains recognized by inhibitory antibodies.

PMID- 16988229
TI  - Growth phase- and nutrient limitation-associated transcript abundance regulation
      in Bordetella pertussis.
AB  - To survive in a host environment, microbial pathogens must sense local
      conditions, including nutrient availability, and adjust their growth state and
      virulence functions accordingly. No comprehensive investigation of growth phase
      related gene regulation in Bordetella pertussis has been reported previously. We
      characterized changes in genome-wide transcript abundance of B. pertussis as a
      function of growth phase and availability of glutamate, a key nutrient for this
      organism. Using a Bordetella DNA microarray, we discovered significant changes in
      transcript abundance for 861 array elements during the transition from log phase
      to stationary phase, including declining transcript levels of many virulence
      factor genes. The responses to glutamate depletion exhibited similarities to the
      responses induced by exit from log phase, including decreased virulence factor
      transcript levels. However, only 23% of array elements that showed at least a
      fourfold growth phase-associated difference in transcript abundance also
      exhibited glutamate depletion-associated changes, suggesting that nutrient
      limitation may be one of several interacting factors affecting gene regulation
      during stationary phase. Transcript abundance patterns of a Bvg+ phase-locked
      mutant revealed that the BvgAS two-component regulatory system is a key
      determinant of growth phase- and nutrient limitation-related transcriptional
      control. Several adhesin genes exhibited lower transcript abundance during
      stationary phase and under glutamate restriction conditions. The predicted
      bacterial phenotype was confirmed: adherence to bronchoepithelial cells decreased
      3.3- and 4.4-fold at stationary phase and with glutamate deprivation,
      respectively. Growth phase and nutrient availability may serve as cues by which
      B. pertussis regulates virulence according to the stage of infection or the
      location within the human airway.

PMID- 16988230
TI  - Anatomical route of invasion and protective mucosal immunity in Trypanosoma cruzi
      conjunctival infection.
AB  - Trypanosoma cruzi is a protozoan parasite that can initiate mucosal infection
      after conjunctival exposure. The anatomical route of T. cruzi invasion and spread
      after conjunctival parasite contamination remains poorly characterized. In the
      present work we have identified the sites of initial invasion and replication
      after contaminative conjunctival challenges with T. cruzi metacyclic
      trypomastigotes using a combination of immunohistochemical and real-time PCR
      confirmatory techniques in 56 mice between 3 and 14 days after challenge. Our
      results demonstrate that the predominant route of infection involves drainage of
      parasites through the nasolacrimal duct into the nasal cavity. Initial parasite
      invasion occurs within the ductal and respiratory epithelia. After successive
      waves of intracellular replication and cell-to-cell spread, parasites drain via
      local lymphatic channels to lymph nodes and then disseminate through the blood to
      distant tissues. This model of conjunctival challenge was used to identify immune
      responses associated with protection against mucosal infection. Preceding mucosal
      infection induces mucosal immunity, resulting in at least 50-fold reductions in
      recoverable tissue parasite DNA in immune mice compared to controls 10 days after
      conjunctival challenge (P < 0.05). Antigen-specific gamma interferon production
      by T cells was increased at least 100-fold in cells harvested from immune mice (P
      < 0.05). Mucosal secretions containing T. cruzi-specific secretory immunoglobulin
      A harvested from immune mice were shown to protect against mucosal parasite
      infection (P < 0.05), demonstrating that mucosal antibodies can play a role in T.
      cruzi immunity. This model provides an important tool for detailed studies of
      mucosal immunity necessary for the development of mucosal vaccines.

PMID- 16988231
TI  - Common and divergent immune response signaling pathways discovered in peripheral
      blood mononuclear cell gene expression patterns in presymptomatic and clinically
      apparent malaria.
AB  - Using genome-wide expression profiles from persons either experimentally
      challenged with malaria-infected mosquitoes or naturally infected with Plasmodium
      falciparum malaria, we present details of the transcriptional changes that occur
      with infection and that either are commonly shared between subjects with
      presymptomatic and clinically apparent malaria or distinguish these two groups.
      Toll-like receptor signaling through NF-kappaB pathways was significantly
      upregulated in both groups, as were downstream genes that function in
      phagocytosis and inflammation, including the cytokines tumor necrosis factor
      alpha, gamma interferon (IFN-gamma), and interleukin-1beta (IL-1beta). The
      molecular program derived from these signatures illuminates the closely
      orchestrated interactions that regulate gene expression by transcription factors
      such as IRF-1 in the IFN-gamma signal transduction pathway. Modulation of
      transcripts in heat shock and glycolytic enzyme genes paralleled the intensity of
      infection. Major histocompatibility complex class I molecules and genes involved
      in class II antigen presentation are significantly induced in 90% of malaria
      infected persons regardless of group. Differences between early presymptomatic
      infection and natural infection involved genes that regulate the induction of
      apoptosis through mitogen-activated protein (MAP) kinases and signaling pathways
      through the endogenous pyrogen IL-1beta, a major inducer of fever. The induction
      of apoptosis in peripheral blood mononuclear cells from patients with naturally
      acquired infection impacted the mitochondrial control of apoptosis and the
      activation of MAP kinase pathways centered around MAPK14 (p38alpha and p38beta).
      Our findings confirm and extend findings regarding aspects of the earliest
      responses to malaria infection at the molecular level, which may be informative
      in elucidating how innate and adaptive immune responses may be modulated in
      different stages of infection.

PMID- 16988232
TI  - Expression of the lipopolysaccharide-modifying enzymes PagP and PagL modulates
      the endotoxic activity of Bordetella pertussis.
AB  - Lipopolysaccharide (LPS) is one of the major constituents of the gram-negative
      bacterial cell envelope. Its endotoxic activity causes the relatively high
      reactogenicity of whole-cell vaccines. Several bacteria harbor LPS-modifying
      enzymes that modulate the endotoxic activity of the LPS. Here we evaluated
      whether two such enzymes, i.e., PagP and PagL, could be useful tools for the
      development of an improved and less reactogenic whole-cell pertussis vaccine. We
      showed that expression of PagP and PagL in Bordetella pertussis leads to
      increased and decreased endotoxic activity of the LPS, respectively. As expected,
      PagP activity also resulted in increased endotoxic activity of whole bacterial
      cells. However, more unexpectedly, this was also the case for PagL. This
      paradoxical result may be explained, in part, by an increased release of LPS,
      which we observed in the PagL-expressing cells.

PMID- 16988233
TI  - Identification of OmpU of Vibrio vulnificus as a fibronectin-binding protein and
      its role in bacterial pathogenesis.
AB  - Vibrio vulnificus is a pathogenic bacterium that causes gastroenteritis and
      primary septicemia. To identify factors involved in microbial adherence to the
      host cells, we investigated bacterial proteins capable of binding to fibronectin,
      one of the main components comprised of the extracellular matrix of mammalian
      cells. A protein of approximately 35 kDa was purified from the extracts of V.
      vulnificus by its property to bind to immobilized fibronectin. This protein was
      identified as OmpU, one of the major outer membrane proteins of V. vulnificus. In
      binding assays using immobilized fibronectin, the number of ompU mutant cells
      bound to fibronectin was only 4% of that of wild-type cells bound to fibronectin.
      In addition, the exogenous addition of antibodies against OmpU resulted in a
      decreased ability of wild-type V. vulnificus to adhere to fibronectin. The ompU
      mutant was also defective in its adherence to RGD tripeptide (5% of the adherence
      of the wild type to RGD), cytoadherence to HEp-2 cells (7% of the adherence of
      the wild type to HEp-2), cytotoxicity to cell cultures (39% of the cytotoxicity
      of the wild type), and mortality in mice (10-fold increase in the 50% lethal
      dose). The ompU mutant complemented with the intact ompU gene restored its
      abilities for adherence to fibronectin, RGD tripeptide, and HEp-2 cells;
      cytotoxicity to HEp-2 cells; and mouse lethality. This study indicates that OmpU
      is an important virulence factor involved in the adherence of V. vulnificus to
      the host cells.

PMID- 16988234
TI  - The C-terminal region of Bacteroides fragilis toxin is essential to its
      biological activity.
AB  - To evaluate the role of the C-terminal region in Bacteroides fragilis toxin (BFT)
      activity, processing, and secretion, sequential C-terminal truncation and point
      mutations were created by site-directed mutagenesis. Determination of BFT
      activity on HT29/C1 cells, cleavage of E-cadherin, and the capacity to induce
      interleukin-8 secretion by wild-type BFT and C-terminal deletion mutants showed
      that deletion of only 2 amino acid residues at the C terminus significantly
      reduced BFT biological activity and deletion of eight or more amino acid residues
      obliterated BFT biologic activity. Western blot and reverse transcription-PCR
      analyses indicated that BFT mutants lacking seven or fewer amino acid residues in
      the C-terminal region are processed and expressed similar to wild-type BFT.
      However, BFT mutants lacking eight or more amino acids at the C terminus are
      expressed similar to wild-type BFT but are unstable. We concluded that the C
      terminus of BFT is not tolerant of modest amino acid deletions, suggesting that
      it is biologically important for BFT activity.

PMID- 16988235
TI  - Chlamydia trachomatis infection induces cleavage of the mitotic cyclin B1.
AB  - The obligate intracellular pathogen Chlamydia trachomatis interferes with a
      number of host cell processes, including cytoskeletal organization, vesicular
      trafficking, and apoptosis. In this study we report that C. trachomatis-infected
      cells proliferate more slowly than uninfected cells, suggesting that C.
      trachomatis may also manipulate the eukaryotic cell cycle. We further demonstrate
      that C. trachomatis infection destabilizes specific cell cycle proteins involved
      in the G2/M transition. C. trachomatis-infected cells, compared to uninfected
      cells, have lower levels of cyclin-dependent kinase 1. Additionally, C.
      trachomatis infection induces an N-terminal truncation of the mitotic cyclin B1.
      Manipulation of the host cell cycle may represent a strategy used by C.
      trachomatis to ensure a stable environment conducive to bacterial growth and
      replication.

PMID- 16988236
TI  - Effects of ompA deletion on expression of type 1 fimbriae in Escherichia coli K1
      strain RS218 and on the association of E. coli with human brain microvascular
      endothelial cells.
AB  - We have previously shown that outer membrane protein A (OmpA) and type 1 fimbriae
      are the bacterial determinants involved in Escherichia coli K1 binding to human
      brain microvascular endothelial cells (HBMEC), which constitute the blood-brain
      barrier. In investigating the role of OmpA in E. coli K1 binding to HBMEC, we
      showed for the first time that ompA deletion decreased the expression of type 1
      fimbriae in E. coli K1. Decreased expression of type 1 fimbriae in the ompA
      deletion mutant was largely the result of driving the fim promoter toward the
      type 1 fimbrial phase-OFF orientation. mRNA levels of fimB and fimE were found to
      be decreased with the OmpA mutant compared to the parent strain. Of interest, the
      ompA deletion further decreased the abilities of E. coli K1 to bind to and invade
      HBMEC under the conditions of fixing type 1 fimbria expression in the phase-ON or
      phase-OFF status. These findings suggest that the decreased ability of the OmpA
      mutant to interact with HBMEC is not entirely due to its decreased type 1
      fimbrial expression and that OmpA and type 1 fimbriae facilitate the interaction
      of E. coli K1 with HBMEC at least in an additive manner.

PMID- 16988237
TI  - Comparison of extracellular and intracellular potency of botulinum neurotoxins.
AB  - Levels of botulinum neurotoxin (BoNT) proteolytic activity were compared using a
      cell-free assay and living neurons to measure extracellular and intracellular
      enzymatic activity. Within the cell-free reaction model, BoNT serotypes A and E
      (BoNT/A and BoNT/E, respectively) were reversibly inhibited by chelating Zn2+
      with N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN). BoNT/E required
      relatively long incubation with TPEN to achieve total inhibition, whereas BoNT/A
      was inhibited immediately upon mixing. When naive Zn2+-containing BoNTs were
      applied to cultured neurons, the cellular action of each BoNT was rapidly
      inhibited by subsequent addition of TPEN, which is membrane permeable. Excess
      Zn2+ added to the culture medium several hours after poisoning fully restored
      intracellular toxin activity. Unlike TPEN, EDTA irreversibly inhibited both
      BoNT/A and -E within the cell-free in vitro reaction. Excess Zn2+ did not
      reactivate the EDTA-treated toxins. However, application of EDTA-treated BoNT/A
      or -E to cultured neurons demonstrated normal toxin action in terms of both
      blocking neurotransmission and SNAP-25 proteolysis. Different concentrations of
      EDTA produced toxin preparations with incrementally reduced in vitro proteolytic
      activities, which, when applied to living neurons showed undiminished cellular
      potency. This suggests that EDTA renders the BoNT proteolytic domain
      conformationally inactive when tested with the cell-free reaction, but this
      change is corrected during entry into neurons. The effect of EDTA is unrelated to
      Zn2+ because TPEN could be applied to living cells before or after poisoning to
      produce rapid and reversible inhibition of both BoNTs. Therefore, bound Zn2+ is
      not required for toxin entry into neurons, and removal of Zn2+ from cytosolic
      BoNTs does not irreversibly alter toxin structure or function. We conclude that
      EDTA directly alters both BoNTs in a manner that is independent of Zn2+.

PMID- 16988238
TI  - The transcriptional regulator RovS controls the attachment of Streptococcus
      agalactiae to human epithelial cells and the expression of virulence genes.
AB  - Streptococcus agalactiae is part of the normal flora of the human
      gastrointestinal tract and also the leading cause of bacterial infections in
      human newborns and immunocompromised adults. The colonization and infection of
      different regions within the human host require a regulatory network in S.
      agalactiae that senses environmental stimuli and controls the formation of
      specific virulence factors. In the present study, we characterized an Rgg-like
      transcriptional regulator, designated RovS (regulator of virulence in
      Streptococcus agalactiae). Deletion of the rovS gene in the genome of S.
      agalactiae resulted in strain 6313 DeltarovS, which exhibited an increased
      attachment to immobilized fibrinogen and a significant increase in adherence to
      the eukaryotic lung epithelial cell line A549. Quantification of expression
      levels of known and putative S. agalactiae virulence genes by real-time PCR
      revealed that RovS influences the expression of fbsA, gbs0230, sodA, rogB, and
      the cyl operon. The altered gene expression in mutant 6313 DeltarovS was restored
      by plasmid-mediated expression of rovS, confirming the RovS deficiency as the
      cause for the observed changes in virulence gene expression in S. agalactiae. DNA
      electrophoretic mobility shift assays showed that RovS specifically binds to the
      promoter regions of fbsA, gbs0230, sodA, and the cyl operon, indicating that RovS
      directly regulates their expression. Deletion and mutation studies in the
      promoter region of fbsA, encoding the main fibrinogen receptor in S. agalactiae,
      identified a RovS DNA motif. Similar motifs were also found in the promoter
      regions of gbs0230, sodA, and the cyl operon, and alignments allowed us to
      propose a consensus sequence for the DNA-binding site of RovS.

PMID- 16988239
TI  - Effects of Psa and F1 on the adhesive and invasive interactions of Yersinia
      pestis with human respiratory tract epithelial cells.
AB  - Yersinia pestis, the causative agent of plague, expresses the Psa fimbriae (pH 6
      antigen) in vitro and in vivo. To evaluate the potential virulence properties of
      Psa for pneumonic plague, an Escherichia coli strain expressing Psa was
      engineered and shown to adhere to three types of human respiratory tract
      epithelial cells. Psa binding specificity was confirmed with Psa-coated
      polystyrene beads and by inhibition assays. Individual Y. pestis cells were found
      to be able to express the capsular antigen fraction 1 (F1) concomitantly with Psa
      on their surface when analyzed by flow cytometry. To better evaluate the separate
      effects of F1 and Psa on the adhesive and invasive properties of Y. pestis,
      isogenic Deltacaf (F1 genes), Deltapsa, and Deltacaf Deltapsa mutants were
      constructed and studied with the three respiratory tract epithelial cells. The
      Deltapsa mutant bound significantly less to all three epithelial cells compared
      to the parental wild-type strain and the Deltacaf and Deltacaf Deltapsa mutants,
      indicating that Psa acts as an adhesin for respiratory tract epithelial cells. An
      antiadhesive effect of F1 was clearly detectable only in the absence of Psa,
      underlining the dominance of the Psa+ phenotype. Both F1 and Psa inhibited the
      intracellular uptake of Y. pestis. Thus, F1 inhibits bacterial uptake by
      inhibiting bacterial adhesion to epithelial cells, whereas Psa seems to block
      bacterial uptake by interacting with a host receptor that doesn't direct
      internalization. The Deltacaf Deltapsa double mutant bound and invaded all three
      epithelial cell types well, revealing the presence of an undefined adhesin(s) and
      invasin(s).

PMID- 16988240
TI  - Measurement of effector protein injection by type III and type IV secretion
      systems by using a 13-residue phosphorylatable glycogen synthase kinase tag.
AB  - Numerous bacterial pathogens use type III secretion systems (T3SSs) or T4SSs to
      inject or translocate virulence proteins into eukaryotic cells. Several different
      reporter systems have been developed to measure the translocation of these
      proteins. In this study, a peptide tag-based reporter system was developed and
      used to monitor the injection of T3S and T4S substrates. The glycogen synthase
      kinase (GSK) tag is a 13-residue phosphorylatable peptide tag derived from the
      human GSK-3beta kinase. Translocation of a GSK-tagged protein into a eukaryotic
      cell results in host cell protein kinase-dependent phosphorylation of the tag,
      which can be detected with phosphospecific GSK-3beta antibodies. A series of
      expression plasmids encoding Yop-GSK fusion proteins were constructed to evaluate
      the ability of the GSK tag to measure the injection of Yops by the Yersinia
      pestis T3SS. GSK-tagged YopE, YopH, LcrQ, YopK, YopN, and YopJ were efficiently
      phosphorylated when translocated into HeLa cells. Similarly, the injection of GSK
      CagA by the Helicobacter pylori T4SS into different cell types was measured via
      phosphorylation of the GSK tag. The GSK tag provides a simple method to monitor
      the translocation of T3S and T4S substrates.

PMID- 16988241
TI  - Porphyromonas gingivalis fimbriae proactively modulate beta2 integrin adhesive
      activity and promote binding to and internalization by macrophages.
AB  - In monocytes, the fimbriae of the oral pathogen Porphyromonas gingivalis activate
      cross talk signaling from Toll-like receptor 2 (TLR2) to the beta2 integrin
      CD11b/CD18, leading to the induction of the high-affinity state of the latter
      receptor. CD14 plays an important role in this "inside-out" proadhesive pathway
      by binding fimbriae and facilitating the activation of TLR2 and
      phosphatidylinositol 3-kinase signaling. In its high-affinity state, CD11b/CD18
      mediates monocyte adhesion to endothelial cells and transmigration to sites of
      infection. We have now shown that P. gingivalis fimbriae function as both an
      activator and a ligand of CD11b/CD18; thus, fimbriae proactively promote their
      own binding to monocytes. Indeed, treatments that interfered with fimbria-induced
      activation of CD11b/CD18 (i.e., blockade of CD14, TLR2, or phosphatidylinositol 3
      kinase signaling) also suppressed the cell binding activity of fimbriae, which
      was largely inducible and CD11b/CD18 dependent. Development of a recombinant
      inside-out signaling system in Chinese hamster ovary cells confirmed the ability
      of fimbriae to activate CD14/TLR2 signaling and induce their own CD11b/CD18
      dependent binding. Induction of this proadhesive pathway by P. gingivalis
      fimbriae appeared to take place in lipid rafts. Indeed, methyl-beta-cyclodextrin,
      a cholesterol-sequestering agent that disrupts lipid raft organization, was found
      to inhibit the fimbria-induced assembly of CD14/TLR2 signaling complexes and the
      activation of the high-affinity state of CD11b/CD18. Experiments using
      macrophages from mice deficient in various pattern recognition receptors
      indicated that the receptors involved in the inside-out proadhesive pathway
      (CD14, TLR2, and CD11b/CD18) are important for mediating P. gingivalis
      internalization within macrophages. It therefore appears that P. gingivalis
      proactively modulates beta2 integrin adhesive activity for intracellular uptake.

PMID- 16988242
TI  - Gingipains from Porphyromonas gingivalis W83 synergistically disrupt endothelial
      cell adhesion and can induce caspase-independent apoptosis.
AB  - We have shown previously that gingipains from Porphyromonas gingivalis W83 can
      induce cell detachment, cell adhesion molecule (CAM) cleavage, and apoptosis in
      endothelial cells; however, the specific roles of the individual gingipains are
      unclear. Using purified gingipains, we determined that each of the gingipains can
      cleave CAMs to varying degrees with differing kinetics. Kgp and HRgpA work
      together to quickly detach endothelial cells. Interestingly, in the absence of
      active caspases, both gingipain-active W83 extracts and purified HRgpA and RgpB
      induce apoptotic morphology, suggesting that the gingipains can induce both
      caspase-dependent and caspase-independent apoptosis. Using z-VAD-FMK to inhibit
      Kgp activity and leupeptin to inhibit Rgp activity in gingipain-active W83
      extracts, we investigated the relative significance of the synergistic role of
      the gingipains. z-VAD-FMK or leupeptin delayed, but did not inhibit, cell
      detachment induced by gingipain-active W83 extracts or purified gingipains. There
      was partial cleavage of N-cadherin and cleavage of VE-cadherin was not inhibited.
      Degradation of integrin beta1 was inhibited only in the presence of z-VAD-FMK.
      These results further clarify the role P. gingivalis plays in tissue destruction
      occurring in the periodontal pocket.

PMID- 16988243
TI  - Protection against lethal challenge with Streptococcus pneumoniae is conferred by
      aryl hydrocarbon receptor activation but is not associated with an enhanced
      inflammatory response.
AB  - Streptococcus pneumoniae is a common respiratory pathogen and a major cause of
      morbidity and mortality in humans, particularly in the elderly and young
      children. The pulmonary immune response to S. pneumoniae is initiated very
      rapidly, and, ideally, innate immune responses are able to contain bacterial
      colonization. In the studies presented here, we sought to determine whether
      activation of the aryl hydrocarbon receptor (AhR) would protect mice from an
      otherwise lethal infection with S. pneumoniae. The rationale for this hypothesis
      is that, although most AhR agonists are potent immunosuppressants, AhR activation
      enhances the inflammatory response to pathogenic and nonpathogenic stimuli.
      Specifically, neutrophil numbers and levels of inflammatory cytokines are often
      increased in mice treated with the potent AhR agonist 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD). To test the hypothesis, vehicle control- or TCDD-treated mice
      were intranasally infected with S. pneumoniae. Mortality, pulmonary bacterial
      burden, cytokine/chemokine levels, and influx of immune cells to the lung were
      analyzed at various times postinfection. As predicted, survival was substantially
      improved in the mice treated with TCDD, and the pulmonary bacterial burden was
      decreased. Surprisingly, however, there was no evidence suggesting that
      protection resulted from an enhanced inflammatory response. In fact, neutrophil
      numbers and inflammatory chemokines and cytokines were all decreased in the TCDD
      treated mice relative to vehicle control-treated mice. This suggests that the
      protective effect of AhR activation is not the result of altered immune function
      but instead may reflect a direct effect on the response of lung cells to
      infection.

PMID- 16988244
TI  - Induction of neutrophil chemotaxis by the quorum-sensing molecule N-(3
      oxododecanoyl)-L-homoserine lactone.
AB  - Acyl homoserine lactones are synthesized by Pseudomonas aeruginosa as signaling
      molecules which control production of virulence factors and biofilm formation in
      a paracrine manner. We found that N-(3-oxododecanoyl)-L-homoserine lactone (3OC12
      HSL), but not its 3-deoxo isomer or acyl-homoserine lactones with shorter fatty
      acids, induced the directed migration (chemotaxis) of human polymorphonuclear
      neutrophils (PMN) in vitro. By use of selective inhibitors a signaling pathway,
      comprising phosphotyrosine kinases, phospholipase C, protein kinase C, and
      mitogen-activated protein kinase C, could be delineated. In contrast to the well
      studied chemokines complement C5a and interleukin 8, the chemotaxis did not
      depend on pertussis toxin-sensitive G proteins, indicating that 3OC12-HSL uses
      another signaling pathway. Strong evidence for the presence of a receptor for
      3OC12-HSL on PMN was derived from uptake studies; by use of radiolabeled 3OC12
      HSL, specific and saturable binding to PMN was seen. Taken together, our data
      provide evidence that PMN recognize and migrate toward a source of 3OC12-HSL
      (that is, to the site of a developing biofilm). We propose that this early
      attraction of PMN could contribute to prevention of biofilm formation.

PMID- 16988245
TI  - Reversible deficiency of antimicrobial polypeptides in bacterial vaginosis.
AB  - Bacterial vaginosis is a common condition associated with increased risk of
      sexually transmitted diseases, including human immunodeficiency virus infections.
      In contrast, vulvovaginal candidiasis has a much weaker association with sexually
      transmitted diseases. We found that vaginal lavage fluid from women with
      bacterial vaginosis is deficient in antimicrobial polypeptides and antimicrobial
      activity compared to fluid from healthy women or women with vulvovaginal
      candidiasis. Effective treatment normalized the concentrations of antimicrobial
      polypeptides in both bacterial vaginosis and in vulvovaginal candidiasis,
      suggesting that the abnormalities were a result of the diseases. Unlike in
      vulvovaginal candidiasis, the neutrophil attractant chemokine interleukin-8 (IL
      8) was not increased in bacterial vaginosis, accounting for low concentrations of
      neutrophil-derived defensins in vaginal fluid. In organotypic cultures of human
      vaginal epithelium containing dendritic cells, treatment with Lactobacillus
      jensenii, a typical vaginal resident, induced the synthesis of IL-8 mRNA and the
      epithelial human beta-defensin-2 mRNA, but a typical bacterial vaginosis
      pathogen, Gardnerella vaginalis, had no effect. When the two bacteria were
      combined, Gardnerella vaginalis did not interfere with the immunostimulatory
      effect of Lactobacillus jensenii. The loss of normal immunostimulatory flora in
      bacterial vaginosis is thus associated with a local deficiency of multiple innate
      immune factors, and this deficiency could predispose individuals to sexually
      transmitted diseases.

PMID- 16988246
TI  - Opsonic antibodies to Enterococcus faecalis strain 12030 are directed against
      lipoteichoic acid.
AB  - A teichoic acid (TA)-like polysaccharide in Enterococcus faecalis has previously
      been shown to induce opsonic antibodies that protect against bacteremia after
      active and passive immunization. Here we present new data providing a corrected
      structure of the antigen and the epitope against which the opsonic antibodies are
      directed. Capsular polysaccharide isolated from E. faecalis strain 12030 by
      enzymatic digestion of peptidoglycan and chromatography (enzyme-TA) was compared
      with lipoteichoic acid (LTA) extracted using butanol and purified by hydrophobic
      interaction chromatography (BuOH-LTA). Structural determinations were carried out
      by chemical analysis and nuclear magnetic resonance spectroscopy. Antibody
      specificity was assessed by enzyme-linked immunosorbent assay and the
      opsonophagocytosis assay. After alanine ester hydrolysis, there was structural
      identity between enzyme-TA and BuOH-LTA of the TA-parts of the two molecules. The
      basic enterococcal LTA structure was confirmed: 1,3-poly(glycerol phosphate)
      nonstoichiometrically substituted at position C-2 of the glycerol residues with d
      Ala and kojibiose. We also detected a novel substituent at position C-2, [D-Ala-
      >6]-alpha-D-Glcp-(1-->2-[D-Ala-->6]-alpha-D-Glcp-1-->). Antiserum raised against
      enzyme-TA bound equally well to BuOH-LTA and dealanylated BuOH-LTA as to the
      originally described enzyme-TA antigen. BuOH-LTA was a potent inhibitor of
      opsonophagocytic killing by the antiserum to enzyme-TA. Immunization with
      antibiotic-killed whole bacterial cells did not induce a significant proportion
      of antibodies directed against alanylated epitopes on the TA, and opsonic
      activity was inhibited completely by both alanylated and dealanylated BuOH-LTA.
      In summary, the E. faecalis strain 12030 enzyme-TA is structurally and
      immunologically identical to dealanylated LTA. Opsonic antibodies to E. faecalis
      12030 are directed predominantly to nonalanylated epitopes on the LTA molecule.

PMID- 16988247
TI  - Control of Borrelia burgdorferi-specific CD4+-T-cell effector function by
      interleukin-12- and T-cell receptor-induced p38 mitogen-activated protein kinase
      activity.
AB  - Infection with Borrelia burgdorferi, the causative agent of Lyme disease, results
      in a Th1 response and proinflammatory cytokine production. Mice deficient for
      MKK3, an upstream activator of p38 mitogen-activated protein (MAP) kinase,
      develop a lower Th1 response and exhibit an impaired ability to produce
      proinflammatory cytokines upon infection with the spirochete. We investigated the
      contribution of p38 MAP kinase activity in gamma interferon (IFN-gamma)
      production in CD4+ T cells in response to specific antigen through T-cell
      receptor (TCR)- and interleukin-12 (IL-12)-mediated signals. The specific
      inhibition of p38 MAP kinase in T cells and the administration of a
      pharmacological inhibitor of the kinase during the course of infection with the
      spirochete resulted in reduced levels of IFN-gamma in the sera of infected mice.
      Our results also demonstrate that although p38 MAP kinase activity is not
      required for the differentiation of B. burgdorferi-specific CD4+ T cells, the
      production of IFN-gamma by Th1 effector cells is regulated by the kinase. Both
      TCR engagement and IL-12 induced the production of the Th1 cytokine through the
      activation of the p38 MAP kinase pathway. Thus, the inhibition of this pathway in
      vitro resulted in decreased levels of IFN-gamma during restimulation of B.
      burgdorferi-specific T cells in response to anti-CD3 and IL-12 stimulation. These
      results clarify the specific contribution of the p38 MAP kinase in the overall
      immune response to the spirochete and its role in the effector function of B.
      burgdorferi-specific T cells.

PMID- 16988248
TI  - Effects of concomitant Schistosoma haematobium infection on the serum cytokine
      levels elicited by acute Plasmodium falciparum malaria infection in Malian
      children.
AB  - Polyparasitism is common in the developing world, and interactions that alter
      disease severity may occur. We previously demonstrated that infection with
      Schistosoma hematobium was associated with protection against Plasmodium
      falciparum infection in children who were 4 to 8 years old. In this study, we
      determined whether underlying helminth infections affected the cytokine responses
      to acute falciparum malaria. A total of 338 schistosomiasis-positive [Sch(+)]
      children who were 4 to 14 years old were matched by age, residence, and sex with
      338 schistosomiasis-negative [Sch(-)] children and monitored for a malaria
      transmission season (25 weeks). Serologic cytokine levels were measured at the
      time of the first clinical malaria episode and in children who did not contract
      malaria. Elevated background levels of interleukin-6 (IL-6) (37.1 pg/ml versus
      10.9 pg/ml [P = 0.04]), IL-4 (27.7 pg/ml versus 6.9 pg/ml [P = 0.02]), IL-10
      (18.2 pg/ml versus 7.2 pg/ml [P < 0.001]), and gamma interferon (18.2 pg/ml
      versus 4.7 pg/ml [P = 0.006]) were noted in Sch(+) children compared to Sch(-)
      children without malaria. IL-6 and IL-10 levels were elevated in association with
      acute malaria, but the levels appeared to be blunted in Sch(+) children compared
      to Sch(-) children who were 4 to 8 years old (for IL-6, 96.2 pg/ml versus 137.2
      pg/ml [P = 0.08]; for IL-10, 195.9 pg/ml versus 282.2 pg/ml [P = 0.06]). The
      level of IL-10 was similarly lower in Sch(+) children than in Sch(-) children who
      were 9 to 14 years old (91.2 pg/ml versus 141.2 pg/ml [P = 0.03]). IL-4 levels
      were inversely correlated with the time until the first malaria infection in both
      the Sch(+) children (P < 0.001) and the Sch(-) children (P < 0.001) who were 4 to
      8 years old. We postulate that the Th2-enriched environment induced by
      schistosomiasis protects against malaria and alters the cytokine milieu during an
      actual infection.

PMID- 16988249
TI  - Cord blood dendritic cell subsets in African newborns exposed to Plasmodium
      falciparum in utero.
AB  - Placental Plasmodium falciparum infection affects birth outcomes and sensitizes
      fetal lymphocytes to parasite antigens. We assessed the influence of maternal P.
      falciparum infection on fetal myeloid dendritic cells (mDC) and plasmacytoid
      dendritic cells (pDC), analyzing the cord blood of offspring of Gabonese mothers
      with different infection histories. Cord blood from newborns of mothers with
      malarial infection at delivery had significantly more mDC than that from
      nonexposed newborns (P = 0.028) but mDC and pDC HLA-DR expression was unrelated
      to maternal infection history. Independently of these findings, cord blood mDC
      and pDC numbers declined significantly as a function of increasing maternal age
      (P = 0.029 and P = 0.033, respectively). The inducible antigen-specific
      interleukin-10-producing regulatory-type T-cell population that we have
      previously detected in cord blood of newborns with prolonged in utero exposure to
      P. falciparum may directly reflect the altered DC numbers in such neonates, while
      the maintenance of cord blood DC HLA-DR expression contrasts with that of DC from
      P. falciparum malaria patients.

PMID- 16988251
TI  - High-affinity interaction between fibronectin and the group B streptococcal C5a
      peptidase is unaffected by a naturally occurring four-amino-acid deletion that
      eliminates peptidase activity.
AB  - The streptococcal C5a peptidase (ScpB) of group B streptococci (GBS) is found in
      virtually all clinical GBS isolates and is required for mucosal colonization in a
      neonatal mouse model. ScpB inhibits neutrophil chemotaxis by enzymatically
      cleaving the complement component C5a. We previously identified a second function
      of ScpB as a fibronectin (Fn) adhesin using phage display. However, phage display
      can identify low-affinity interactions. We therefore measured the affinity of
      both full-length recombinant ScpB (FL-ScpB) and the 110-amino-acid phage display
      fragment (Scp-PDF) for immobilized Fn using surface plasmon resonance. The
      affinity for Fn was very high for both FL-ScpB (equilibrium dissociation constant
      [KD] = 4.0 nM) and Scp-PDF (KD = 4.4 nM) and is consistent with a biologically
      significant role for the adhesin activity of ScpB. We also studied the Fn adhesin
      activity of a common natural variant of ScpB (ScpBDelta) that contains a 4-amino
      acid deletion that eliminates peptidase activity. The integrity of scpB is
      otherwise maintained, suggesting that the Fn adhesin activity of ScpB may be
      responsible for its conservation in these strains. The affinities of both FL
      ScpBDelta (KD = 2.4 nM) and ScpBDelta-PDF (KD = 1.4 nM) for Fn are unaffected by
      the deletion. Complementation in trans by both scpB and scpBDelta corrected the
      Fn-binding defect of an scpB deletion mutant GBS strain to an identical degree.
      The high affinity of ScpB for Fn and the maintenance of this affinity in
      ScpBDelta support our hypothesis that the Fn adhesin activity of scpB plays a
      role in virulence.

PMID- 16988250
TI  - Role of eosinophils and neutrophils in innate and adaptive protective immunity to
      larval strongyloides stercoralis in mice.
AB  - The goal of this study was to determine the roles of eosinophils and neutrophils
      in innate and adaptive protective immunity to larval Strongyloides stercoralis in
      mice. The experimental approach used was to treat mice with an anti-CCR3
      monoclonal antibody to eliminate eosinophils or to use CXCR2-/- mice, which have
      a severe neutrophil recruitment defect, and then determine the effect of the
      reduction or elimination of the particular cell type on larval killing. It was
      determined that eosinophils killed the S. stercoralis larvae in naive mice,
      whereas these cells were not required for the accelerated killing of larvae in
      immunized mice. Experiments using CXCR2-/- mice demonstrated that the reduction
      in recruitment of neutrophils resulted in significantly reduced innate and
      adaptive protective immunity. Protective antibody developed in the immunized
      CXCR2-/- mice, thereby demonstrating that neutrophils were not required for the
      induction of the adaptive protective immune response. Moreover, transfer of
      neutrophil-enriched cell populations recovered from either wild-type or CXCR2-/-
      mice into diffusion chambers containing larvae demonstrated that larval killing
      occurred with both cell populations when the diffusion chambers were implanted in
      immunized wild-type mice. Thus, the defect in the CXCR2-/- mice was a defect in
      the recruitment of the neutrophils and not a defect in the ability of these cells
      to kill larvae. This study therefore demonstrated that both eosinophils and
      neutrophils are required in the protective innate immune response, whereas only
      neutrophils are necessary for the protective adaptive immune response to larval
      S. stercoralis in mice.

PMID- 16988252
TI  - A new immunoglobulin-binding protein, EibG, is responsible for the chain-like
      adhesion phenotype of locus of enterocyte effacement-negative, shiga toxin
      producing Escherichia coli.
AB  - Shiga toxin-producing Escherichia coli (STEC) are important enteropathogens
      causing severe diseases such as hemorrhagic colitis and hemolytic-uremic syndrome
      in humans. The majority of STEC strains of serogroups O157, O26, or O111
      associated with severe cases of these diseases possess a pathogenicity island
      termed the locus of enterocyte effacement (LEE). LEE, which is responsible for
      the formation of attaching-and-effacing lesions on intestinal epithelial cells,
      is important for the full virulence of STEC. Nonetheless, LEE-negative STEC
      strains have repeatedly been reported to be associated with severe diseases in
      humans. In this study, we characterized adhesion to cultured epithelial cells of
      certain LEE-negative STEC isolated from humans with or without bloody diarrhea.
      Several LEE-negative STEC belonging to serogroup O91 showed an unusual, chain
      like adhesion pattern to HEp-2 cells. Using Tn5-based transposon mutagenesis, we
      identified the gene essential for the chain-like adhesion phenotype of this O91
      STEC strain. Sequence analysis of the Tn5-inserted allele identified a novel
      chromosomal open reading frame (ORF) encoding a polypeptide with a high degree of
      similarity to the E. coli immunoglobulin-binding (Eib) proteins EibA, -C, -D, -E,
      and -F. Therefore, the ORF was designated EibG. Laboratory E. coli strain MC4100
      transformed with a multicopy plasmid carrying eibG showed chain-like adhesion to
      HEp-2 cells, and whole-cell lysates of the strain bound to human-derived
      immunoglobulin G (IgG) Fc and IgA. These results indicate that EibG acts as an
      IgG Fc- and IgA-binding protein, as well as an adhesin of LEE-negative STEC.

PMID- 16988253
TI  - Structural characterization of peptide-mediated inhibition of Porphyromonas
      gingivalis biofilm formation.
AB  - Porphyromonas gingivalis is a periodontal pathogen whose primary niche is the
      anaerobic environment of subgingival dental plaque, but initial colonization of
      the oral cavity is likely to occur on supragingival surfaces that already support
      robust biofilm communities. Our studies have shown that P. gingivalis adheres to
      Streptococcus gordonii through interaction of the minor fimbrial antigen Mfa1
      with a specific region of the streptococcal SspB polypeptide (residues 1167 to
      1193) designated BAR. We show that a synthetic peptide comprising the BAR
      sequence potently inhibits P. gingivalis adherence to S. gordonii (50% inhibitory
      concentration = 1.3 microM) and prevents the development of P. gingivalis
      biofilms. However, a retroinverso peptide that possessed the same side chain
      topology as that of BAR was inactive, suggesting that interactions of Mfa1 with
      the peptide backbone of BAR are important for binding. A conformationally
      constrained analog of BAR inhibited P. gingivalis adherence and biofilm formation
      but at a lower specific activity than that of BAR. Therefore, to further define
      the structural features of the Mfa1-BAR interaction, we functionally screened
      combinatorial libraries of BAR in which active site residues (Asn1182, Thr1184,
      and Val1185) were replaced with each of the 19 common amino acids. Peptides
      containing positively charged amino acids at position 1182 or hydrophobic
      residues at position 1185 bound P. gingivalis more efficiently than did control
      peptides containing Asn and Val at these positions, suggesting that electrostatic
      and hydrophobic interactions may contribute to Mfa1-SspB binding. In contrast,
      replacement of Pro or Gly at these positions was detrimental to adherence,
      suggesting that perturbation of the BAR secondary structure influences activity.
      The net effect of substitutions for Thr1184 was less pronounced either positively
      or negatively than that at the other sites. These results define physicochemical
      characteristics of the interacting interface of Mfa1 and SspB and suggest that
      peptides or peptidomimetics with greater specific inhibitory activity than that
      of BAR can be developed. These compounds may represent potential therapeutics
      that target some of the first molecular interactions that allow P. gingivalis to
      colonize the oral cavity.

PMID- 16988254
TI  - Mutations within the catalytic motif of DNA adenine methyltransferase (Dam) of
      Aeromonas hydrophila cause the virulence of the Dam-overproducing strain to
      revert to that of the wild-type phenotype.
AB  - In this study, we demonstrated that the methyltransferase activity associated
      with Dam was essential for attenuation of Aeromonas hydrophila virulence. We
      mutated aspartic acid and tyrosine residues to alanine within the conserved DPPY
      catalytic motif of Dam and transformed the pBAD/damD/A, pBAD/damY/A, and
      pBAD/damAhSSU (with the native dam gene) recombinant plasmids into the
      Escherichia coli GM33 (dam-deficient) strain. Genomic DNA (gDNA) isolated from
      either of the E. coli GM33 strains harboring the pBAD vector with the mutated dam
      gene was resistant to DpnI digestion and sensitive to DpnII restriction
      endonuclease cutting. These findings were contrary to those with the gDNA of E.
      coli GM33 strain containing the pBAD/damAhSSU plasmid, indicating nonmethylation
      of E. coli gDNA with mutated Dam. Overproduction of mutated Dam in A. hydrophila
      resulted in bacterial motility, hemolytic and cytotoxic activities associated
      with the cytotoxic enterotoxin (Act), and protease activity similar to that of
      the wild-type (WT) bacterium, which harbored the pBAD vector and served as a
      control strain. On the contrary, overproduction of native Dam resulted in
      decreased bacterial motility, increased Act-associated biological effects, and
      increased protease activity. Lactone production, an indicator of quorum sensing,
      was increased when the native dam gene was overexpressed, with its levels
      returning to that of the control strain when the dam gene was mutated. These
      effects of Dam appeared to be mediated through a regulatory glucose-inhibited
      division A protein. Infection of mice with the mutated Dam-overproducing strains
      resulted in mortality rates similar to those for the control strain, with 100% of
      the animals dying within 2 to 3 days with two 50% lethal doses (LD50s) of the WT
      bacterium. Importantly, immunization of mice with a native-Dam-overproducing
      strain at the same LD50 did not result in any lethality and provided protection
      to animals after subsequent challenge with a lethal dose of the control strain.

PMID- 16988255
TI  - Trichomonas vaginalis lipophosphoglycan triggers a selective upregulation of
      cytokines by human female reproductive tract epithelial cells.
AB  - Trichomonas vaginalis is one of the most common nonviral sexually transmitted
      human infections and, worldwide, has been linked to increased incidence of human
      immunodeficiency virus type 1 transmission, preterm delivery, low birth weight,
      cervical cancer, and vaginitis. The molecular pathways that are important in
      initiating host inflammatory and immune responses to T. vaginalis are poorly
      understood. Here we report interactions of human cervicovaginal epithelial cells
      with the most abundant cell surface glycoconjugate of the parasite, the T.
      vaginalis lipophosphoglycan (LPG). Purified LPG mediated the adhesion of
      parasites to human vaginal epithelial cells in a dose-dependent manner.
      Furthermore, T. vaginalis LPG (but not LPG from Tritrichomonas foetus, the
      causative agent of bovine trichomoniasis) induced a selective upregulation of
      chemotactic cytokines by human endocervical, ectocervical, and vaginal epithelial
      cells, which do not express Toll-like receptor 4/MD2. The T. vaginalis LPG
      triggered interleukin 8 (IL-8), which promotes the adhesion and transmigration of
      neutrophils across the endothelium, and macrophage inflammatory protein 3alpha,
      which is a chemoattractant for immune cells and is essential for dendritic cell
      maturation. These effects were dose dependent and sustained in the absence of
      cytotoxicity and IL-1beta release and utilized, at least in part, a signaling
      pathway independent from the Toll-like/IL-1 receptor adaptor protein MyD88.

PMID- 16988257
TI  - Organ- and disease-stage-specific regulation of Toxoplasma gondii-specific CD8-T
      cell responses by CD4 T cells.
AB  - Toxoplasma gondii induces a persistent central nervous system infection, which
      may be lethally reactivated in AIDS patients with low CD4 T-cell numbers. To
      analyze the role of CD4 T cells for the regulation of parasite-specific CD8 T
      cells, mice were infected with transgenic T. gondii expressing the CD8 T-cell
      antigen beta-galactosidase (beta-Gal). Depletion of CD4 T cells prior to
      infection did not affect frequencies of beta-Gal(876-884)-specific (consisting of
      residues 876 to 884 of beta-Gal) CD8 T cells but resulted in a pronounced
      reduction of intracerebral beta-Gal-specific gamma interferon (IFN-gamma)
      producing and cytolytic CD8 T cells. After cessation of anti-CD4 treatment a
      normal T. gondii-specific CD4 T-cell response developed, but IFN-gamma production
      of intracerebral beta-Gal-specific CD8 T cells remained impaired. The important
      supportive role of CD4 T cells for the optimal functional activity of
      intracerebral CD8 T cells was also observed in mice that had been depleted of CD4
      T cells during chronic toxoplasmosis. Reinfection of chronically infected mice
      that had been depleted of CD4 T cells during either the acute or chronic stage of
      infection resulted in an enhanced proliferation of beta-Gal-specific IFN-gamma
      producing splenic CD8 T cells. However, reinfection of chronically infected mice
      that had been depleted of CD4 T cells in the acute stage of infection did not
      reverse the impaired IFN-gamma production of intracerebral CD8 T cells.
      Collectively, these findings illustrate that CD4 T cells are not required for the
      induction and maintenance of parasite-specific CD8 T cells but, depending on the
      stage of infection, the infected organ and parasite challenge infection regulate
      the functional activity of intracerebral CD8 T cells.

PMID- 16988256
TI  - Interleukin-10 anti-inflammatory response to Borrelia burgdorferi, the agent of
      Lyme disease: a possible role for suppressors of cytokine signaling 1 and 3.
AB  - It has been established that interleukin-10 (IL-10) inhibits inflammatory
      cytokines produced by macrophages in response to Borrelia burgdorferi or its
      lipoproteins. The mechanism by which IL-10 exerts this anti-inflammatory effect
      is still unknown. Recent findings indicate that suppressors of cytokine signaling
      (SOCS) proteins are induced by cytokines and Toll-like receptor (TLR)-mediated
      stimuli, and in turn they can down-regulate cytokine and TLR signaling in
      macrophages. Because it is known that SOCS are induced by IL-10 and that B.
      burgdorferi and its lipoproteins most likely interact via TLR2 or the
      heterodimers TLR2/1 and/or TLR2/6, we hypothesized that SOCS are induced by IL-10
      and B. burgdorferi and its lipoproteins in macrophages and that SOCS may mediate
      the inhibition by IL-10 of concomitantly elicited cytokines. We report here that
      mouse J774 macrophages incubated with IL-10 and added B. burgdorferi spirochetes
      (freeze-thawed, live, or sonicated) or lipidated outer surface protein A (L-OspA)
      augmented their SOCS1/SOCS3 mRNA and protein expression, with SOCS3 being more
      abundant. Pam(3)Cys, a synthetic lipopeptide, also induced SOCS1/SOCS3 expression
      under these conditions, but unlipidated OspA was ineffective. Neither endogenous
      IL-10 nor the translation inhibitor cycloheximide blocked SOCS1/SOCS3 induction
      by B. burgdorferi and its lipoproteins, indicating that the expression of other
      genes is not required. This temporally correlated with the IL-10-mediated
      inhibition of the inflammatory cytokines IL-1beta, IL-6, IL-12p40, IL-18, and
      tumor necrosis factor alpha. Our data are evidence to suggest that expression of
      SOCS is part of the mechanism of IL-10-mediated inhibition of inflammatory
      cytokines elicited by B. burgdorferi and its lipoproteins.

PMID- 16988258
TI  - Multivalent recombinant protein vaccine against coccidioidomycosis.
AB  - Coccidioidomycosis is a human respiratory disease that is endemic to the
      southwestern United States and is caused by inhalation of the spores of a desert
      soilborne fungus. Efforts to develop a vaccine against this disease have focused
      on identification of T-cell-reactive antigens derived from the parasitic cell
      wall which can stimulate protective immunity against Coccidioides posadasii
      infection in mice. We previously described a productive
      immunoproteomic/bioinformatic approach to the discovery of vaccine candidates
      which makes use of the translated genome of C. posadasii and a computer-based
      method of scanning deduced sequences of seroreactive proteins for epitopes that
      are predicted to bind to human major histocompatibility (MHC) class II-restricted
      molecules. In this study we identified a set of putative cell wall proteins
      predicted to contain multiple, promiscuous MHC II binding epitopes. Three of
      these were expressed by Escherichia coli, combined in a vaccine, and tested for
      protective efficacy in C57BL/6 mice. Approximately 90% of the mice survived
      beyond 90 days after intranasal challenge, and the majority cleared the pathogen.
      We suggest that the multicomponent vaccine stimulates a broader range of T-cell
      clones than the single recombinant protein vaccines and thereby may be capable of
      inducing protection in an immunologically heterogeneous human population.

PMID- 16988259
TI  - Mapping of the Plasmodium chabaudi resistance locus char2.
AB  - Animals congenic for the char2 host response locus to the murine malarial
      parasite Plasmodium chabaudi have been bred, and they demonstrated a phenotypic
      difference from the parental lines. These congenic lines have been crossed back
      to the parental line to generate recombinants across the congenic intervals. The
      recombinants were inbred, and the subcongenic intervals were fixed. These lines
      were then challenged with parasites and assessed as being either resistant or
      susceptible. From the analysis of many subcongenic lines, it has become obvious
      that there are at least two loci underlying the char2 locus and that both of
      these mediate resistance when the haplotype derives from the resistant C57BL/6
      strain.

PMID- 16988260
TI  - Comparison of protective efficacy of subcutaneous versus intranasal immunization
      of mice with a Brucella melitensis lipopolysaccharide subunit vaccine.
AB  - Groups of mice were immunized either subcutaneously or intranasally with purified
      Brucella melitensis lipopolysaccharide (LPS) or with LPS as a noncovalent complex
      with Neisseria meningitidis group B outer membrane protein (LPS-GBOMP). Control
      mice were inoculated with sterile saline. Two doses of vaccine were given 4 weeks
      apart. Mice were challenged intranasally with virulent B. melitensis strain 16M 4
      weeks after the second dose of vaccine. Sera, spleens, lungs, and livers of mice
      were harvested 8 weeks after challenge. The bacterial loads in the organs were
      determined by culture on brucella agar plates. Protective efficacy was determined
      by comparing the clearance of bacteria from organs of immunized mice with the
      clearance of bacteria from organs of control mice. At 8 weeks postchallenge there
      was significant protection from disseminated infection of spleens and livers of
      mice intranasally immunized with either vaccine compared to infection of control
      mice (P < 0.01). There was no significant difference in clearance of bacteria
      from the lungs of immunized mice and control mice. However, mice immunized
      subcutaneously with either LPS or LPS-GBOMP vaccine showed significant protection
      against infection of the spleen (P < 0.001), liver (P < 0.001), and lungs (P <
      0.05). These results show that intranasal immunization of mice with either
      vaccine provided significant protection against disseminated infection of the
      spleen and liver but subcutaneous immunization of mice with the vaccines
      conferred significant protection against infection of the spleen, liver, and
      lungs.

PMID- 16988261
TI  - Optimization of the delivery of heterologous proteins by the Salmonella enterica
      serovar Typhimurium type III secretion system for vaccine development.
AB  - Type III protein secretion systems, which are organelles with the capacity to
      deliver bacterial proteins into host cells, have been adapted to deliver
      heterologous antigens for vaccine development. A limitation of these antigen
      delivery systems is that some proteins are not amenable to secretion through this
      pathway. We show here that proteins from the simian and human immunodeficiency
      viruses that are not permissive for secretion through a Salmonella enterica
      serovar Typhimurium type III secretion system can be modified to travel this
      secretion pathway by introduction of discrete mutations. Proteins optimized for
      secretion were presented more efficiently via the major histocompatibility
      complex class I pathway and were able to induce a better immune response.

PMID- 16988262
TI  - Transcutaneous immunization with toxin-coregulated pilin A induces protective
      immunity against Vibrio cholerae O1 El Tor challenge in mice.
AB  - Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV
      bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated
      pilus is involved in formation of microcolonies of V. cholerae at the intestinal
      surface, and strains of V. cholerae deficient in TcpA are attenuated and unable
      to colonize intestinal surfaces. Anti-TcpA immunity is common in humans
      recovering from cholera in Bangladesh, and immunization against TcpA is
      protective in murine V. cholerae models. To evaluate whether transcutaneously
      applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of
      TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], 50 mug) on days 0, 19,
      and 40. Mice immunized with TcpA alone did not develop anti-TcpA responses. Mice
      that received transcutaneously applied TcpA and CT developed prominent anti-TcpA
      immunoglobulin G (IgG) serum responses but minimal anti-TcpA IgA. Transcutaneous
      immunization with CT induced prominent IgG and IgA anti-CT serum responses. In an
      infant mouse model, offspring born to dams transcutaneously immunized either with
      TcpA and CT or with CT alone were challenged with 10(6) CFU (one 50% lethal dose)
      wild-type V. cholerae O1 El Tor strain N16961. At 48 h, mice born to females
      transcutaneously immunized with CT alone had 36% +/- 10% (mean +/- standard error
      of the mean) survival, while mice born to females transcutaneously immunized with
      TcpA and CT had 69% +/- 6% survival (P < 0.001). Our results suggest that
      transcutaneous immunization with TcpA and an immunoadjuvant induces protective
      anti-TcpA immune responses. Anti-TcpA responses may contribute to an optimal
      cholera vaccine.

PMID- 16988263
TI  - Prophylaxis and therapy of inhalational anthrax by a novel monoclonal antibody to
      protective antigen that mimics vaccine-induced immunity.
AB  - The neutralizing antibody response to the protective antigen (PA) component of
      anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for
      vaccine-mediated protection against anthrax. We reasoned that a human anti-PA
      monoclonal antibody (MAb) selected on the basis of superior toxin neutralization
      activity might provide potent protection against anthrax. The fully human MAb
      (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti
      PA human MAbs generated using transgenic mice immunized with recombinant PA
      solely on the basis of in vitro anthrax toxin neutralization. This MAb was
      effective in prophylactic and postsymptomatic treatment of rabbits exposed to
      aerosolized anthrax spores, and a single intramuscular injection of 1 mg/kg of
      body weight fully protected cynomolgus monkeys challenged with aerosolized
      anthrax spores. Importantly, MAb 1303 defines a novel neutralizing epitope that
      requires Fc receptor engagement for maximal activity. F(ab')2 fragments of MAb
      1303, which retain equivalent affinity for PA, are 10- to 100-fold less potent in
      neutralizing anthrax toxin in vitro. Addition of Fc receptor-blocking antibodies
      also greatly reduced the activity of MAb 1303. Moreover, we found that the
      neutralizing activity of mouse, rabbit, and human antisera elicited by PA
      vaccines was effectively abrogated by blocking Fc receptors. Selection of an anti
      PA MAb by using a functional assay that is a surrogate for protection has
      resulted in the identification of a fully human MAb with potent activity in vivo
      and uncovered a previously unrecognized mechanism of antibody-mediated toxin
      neutralization that is important for currently used anthrax vaccines.

PMID- 16988264
TI  - Effects of temperature on gene expression patterns in Leptospira interrogans
      serovar Lai as assessed by whole-genome microarrays.
AB  - Leptospirosis is an important zoonosis of worldwide distribution. Humans become
      infected via exposure to pathogenic Leptospira spp. from infected animals or
      contaminated water or soil. The availability of genome sequences for Leptospira
      interrogans, serovars Lai and Copenhageni, has opened up opportunities to examine
      global transcription profiles using microarray technology. Temperature is a key
      environmental factor known to affect leptospiral protein expression. Leptospira
      spp. can grow in artificial media at a range of temperatures reflecting
      conditions found in the environment and the mammalian host. Therefore,
      transcriptional changes were compared between cultures grown at 20 degrees C, 30
      degrees C, 37 degrees C, and 39 degrees C to represent ambient temperatures in
      the environment, growth under laboratory conditions, and temperatures in healthy
      and febrile hosts. Data from direct pairwise comparisons of the four temperatures
      were consolidated to examine transcriptional changes at two generalized
      biological conditions representing mammalian physiological temperatures (37
      degrees C and 39 degrees C) versus environmental temperatures (20 degrees C and
      30 degrees C). Additionally, cultures grown at 30 degrees C then shifted
      overnight to 37 degrees C were compared with those grown long-term at 30 degrees
      C and 37 degrees C to identify genes potentially expressed in the early stages of
      infection. Comparison of data sets from physiological versus environmental
      experiments with upshift experiments provided novel insights into possible
      transcriptional changes at different stages of infection. Changes included
      differential expression of chemotaxis and motility genes, signal transduction
      systems, and genes encoding proteins involved in alteration of the outer
      membrane. These findings indicate that temperature is an important factor
      regulating expression of proteins that facilitate invasion and establishment of
      disease.

PMID- 16988265
TI  - Characterization of igaB, a second immunoglobulin A1 protease gene in nontypeable
      Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae is an important respiratory pathogen, causing
      otitis media in children and lower respiratory tract infection in adults with
      chronic obstructive pulmonary disease (COPD). Immunoglobulin A1 (IgA1) protease
      is a well-described protein and potential virulence factor in this organism as
      well as other respiratory pathogens. IgA1 proteases cleave human IgA1, are
      involved in invasion, and display immunomodulatory effects. We have identified a
      second IgA1 protease gene, igaB, in H. influenzae that is present in addition to
      the previously described IgA1 protease gene, iga. Reverse transcriptase PCR and
      IgA1 protease assays indicated that the gene is transcribed, expressed, and
      enzymatically active in H. influenzae. The product of this gene is a type 2 IgA1
      protease with homology to the iga gene of Neisseria species. Mutants that were
      deficient in iga, igaB, and both genes were constructed in H. influenzae strain
      11P6H, a strain isolated from a patient with COPD who was experiencing an
      exacerbation. Analysis of these mutants indicated that igaB is the primary
      mediator of IgA1 protease activity in this strain. IgA1 protease activity assays
      on 20 clinical isolates indicated that the igaB gene is associated with increased
      levels of IgA1 protease activity. Approximately one-third of 297 strains of H.
      influenzae of diverse clinical and geographic origin contained igaB. Significant
      differences in the prevalence of igaB were observed among isolates from different
      sites of isolation (sputum > middle ear > nasopharynx). These data support the
      hypothesis that the newly discovered igaB gene is a potential virulence factor in
      nontypeable H. influenzae.

PMID- 16988266
TI  - Protective antigen as a correlative marker for anthrax in animal models.
AB  - The most aggressive form of anthrax results from inhalation of airborne spores of
      Bacillus anthracis and usually progresses unnoticed in the early stages because
      of unspecific symptoms. The only reliable marker of anthrax is development of
      bacteremia, which increases with disease progress. Rapid diagnosis of anthrax is
      imperative for efficient treatment and cure. Herein we demonstrate that the
      presence and level of a bacterial antigen, the protective antigen (PA), a
      component of B. anthracis toxins, in host sera can serve as a reliable marker of
      infection. This was tested in two animal models of inhalation anthrax, rabbits
      and guinea pigs infected by intranasal instillation of Vollum spores. In both
      models, we demonstrated qualitative and quantitative correlations between levels
      of bacteremia and PA concentrations in the sera of sick animals. The average time
      to death in infected animals was about 16 h after the appearance of bacteremia,
      leaving a small therapeutic window. As the time required for immunodetection of
      PA can be very short, the use of this marker will be beneficial for faster
      diagnosis and treatment of inhalation anthrax.

PMID- 16988267
TI  - Characterization and regulation of the trehalose synthesis pathway and its
      importance in the pathogenicity of Cryptococcus neoformans.
AB  - The disaccharide trehalose has been found to play diverse roles, from energy
      source to stress protectant, and this sugar is found in organisms as diverse as
      bacteria, fungi, plants, and invertebrates but not in mammals. Recent studies in
      the pathobiology of Cryptococcus neoformans identified the presence of a
      functioning trehalose pathway during infection and suggested its importance for
      C. neoformans survival in the host. Therefore, in C. neoformans we created null
      mutants of the trehalose-6-phosphate (T6P) synthase (TPS1), trehalose-6-phophate
      phosphatase (TPS2), and neutral trehalase (NTH1) genes. We found that both TPS1
      and TPS2 are required for high-temperature (37 degrees C) growth and glycolysis
      but that the block at TPS2 results in the apparent toxic accumulation of T6P,
      which makes this enzyme a fungicidal target. Sorbitol suppresses the growth
      defect in the tps1 and tps2 mutants at 37 degrees C, which supports the
      hypothesis that these sugars (trehalose and sorbitol) act primarily as stress
      protectants for proteins and membranes during exposure to high temperatures in C.
      neoformans. The essential nature of this pathway for disease was confirmed when a
      tps1 mutant strain was found to be avirulent in both rabbits and mice.
      Furthermore, in the system of the invertebrate C. elegans, in which high in vivo
      temperature is no longer an environmental factor, attenuation in virulence was
      still noted with the tps1 mutant, and this supports the hypothesis that the
      trehalose pathway in C. neoformans is involved in more host survival mechanisms
      than simply high-temperature stresses and glycolysis. These studies in C.
      neoformans and previous studies in other pathogenic fungi support the view of the
      trehalose pathway as a selective fungicidal target for use in antifungal
      development.

PMID- 16988268
TI  - Immunization with polyamine transport protein PotD protects mice against systemic
      infection with Streptococcus pneumoniae.
AB  - The human pathogen Streptococcus pneumoniae contains genes for a putative
      polyamine ABC transporter which are organized in an operon and designated
      potABCD. Polyamine transport protein D (PotD) is an extracellular protein which
      binds polyamines and possibly other structurally related molecules. PotD has been
      shown to contribute to virulence in both a murine sepsis model and a pneumonia
      model with capsular type 3 pneumococci. The protective efficacy of recombinant
      PotD was evaluated by active immunization and intravenous challenge with capsular
      type 3 pneumococci in CBA/N mice. Immunized mice had 91.7% survival following
      lethal pneumococcal challenge, compared with 100% mortality in the control group.
      Immunized animals had high-titer anti-PotD antibodies following three
      immunizations with alum. Protection in a sepsis model was also seen after passive
      administration of rabbit antiserum raised against PotD (P < 0.004). These results
      suggest that antibodies to PotD confer protection against invasive pneumococcal
      disease and that this protein should be studied further as a potential vaccine
      candidate for protection against invasive pneumococcal infections.

PMID- 16988269
TI  - Pseudomonas aeruginosa infection of airway epithelial cells modulates expression
      of Kruppel-like factors 2 and 6 via RsmA-mediated regulation of type III
      exoenzymes S and Y.
AB  - Pseudomonas aeruginosa is an important opportunistic pathogen which is capable of
      causing both acute and chronic infections in immunocompromised patients.
      Successful adaptation of the bacterium to its host environment relies on the
      ability of the organism to tightly regulate gene expression. RsmA, a small RNA
      binding protein, controls the expression of a large number of virulence-related
      genes in P. aeruginosa, including those encoding the type III secretion system
      and associated effector proteins, with important consequences for epithelial cell
      morphology and cytotoxicity. In order to examine the influence of RsmA-regulated
      functions in the pathogen on gene expression in the host, we compared global
      expression profiles of airway epithelial cells in response to infection with P.
      aeruginosa PAO1 and an rsmA mutant. The RsmA-dependent response of host cells was
      characterized by significant changes in the global transcriptional pattern,
      including the increased expression of two Kruppel-like factors, KLF2 and KLF6.
      This increased expression was mediated by specific type III effector proteins.
      ExoS was required for the enhanced expression of KLF2, whereas both ExoS and ExoY
      were required for the enhanced expression of KLF6. Neither ExoT nor ExoU
      influenced the expression of the transcription factors. Additionally, the
      increased gene expression of KLF2 and KLF6 was associated with ExoS-mediated
      cytotoxicity. Therefore, this study identifies for the first time the human
      transcription factors KLF2 and KLF6 as targets of the P. aeruginosa type III
      exoenzymes S and Y, with potential importance in host cell death.

PMID- 16988270
TI  - Rapid development of a gamma interferon-secreting glycolipid/CD1d-specific
      Valpha14+ NK1.1- T-cell subset after bacterial infection.
AB  - The phenotypic and functional changes of glycolipid presented by
      CD1d(glycolipid/CD1d) specific Valpha14+ T cells in the liver of mice at early
      stages of bacterial infection were investigated. After Listeria monocytogenes
      infection or interleukin-12 (IL-12) treatment, alpha-galactosylceramide/CD1d
      tetramer-reactive (alpha-GalCer/CD1d+) T cells coexpressing natural killer (NK)
      1.1 marker became undetectable and, concomitantly, cells lacking NK1.1 emerged in
      both euthymic and thymectomized animals. Depletion of the NK1.1+ subpopulation
      prevented the emergence of alpha-GalCer/CD1d+ NK1.1- T cells. Before infection,
      NK1.1+, rather than NK1.1-, alpha-GalCer/CD1d+ T cells coexpressing CD4 were
      responsible for IL-4 production, whereas gamma interferon (IFN-gamma) was
      produced by cells regardless of NK1.1 or CD4 expression. After infection, IL-4
      secreting cells became undetectable among alpha-GalCer/CD1d+ T cells, but
      considerable numbers of IFN-gamma-secreting cells were found among NK1.1-, but
      not NK1.1+, cells lacking CD4. Thus, NK1.1 surface expression and functional
      activities of Valpha14+ T cells underwent dramatic changes at early stages of
      listeriosis, and these alterations progressed in a thymus-independent manner. In
      mutant mice lacking all alpha-GalCer/CD1d+ T cells listeriosis was ameliorated,
      suggesting that the subtle contribution of the NK1.1- T-cell subset to
      antibacterial protection is covered by more profound detrimental effects of the
      NK1.1+ T-cell subset.

PMID- 16988271
TI  - Down-regulation of key virulence factors makes the Salmonella enterica serovar
      Typhimurium rfaH mutant a promising live-attenuated vaccine candidate.
AB  - Mutants of Salmonella enterica serovar Typhimurium that lack the transcriptional
      regulator RfaH are efficient as live oral vaccines against salmonellosis in mice.
      We show that the attenuation of the vaccine candidate strain is associated with
      reduced net growth in epithelial and macrophage cells. In order to identify the
      relevant RfaH-dependent genes, the RfaH regulon was determined with S. enterica
      serovars Enteritidis and Typhimurium using whole-genome Salmonella microarrays.
      As well as impacting the expression of genes involved in lipopolysaccharide (LPS)
      core and O-antigen synthesis, the loss of RfaH results in a marked down
      regulation of SPI-4 genes, the flagellum/chemotaxis system, and type III
      secretion system 1. However, a proportion of these effects could have been the
      indirect consequence of the altered expression of genes required for LPS
      biosynthesis. Direct and indirect effects of the rfaH mutation were dissociated
      by genome-wide transcriptional profiling of a structural deep-rough LPS mutant
      (waaG). We show that truncation of LPS itself is responsible for the decreased
      intracellular yield observed for DeltarfaH strains. LPS mutants do not differ in
      replication ability; rather, they show increased susceptibility to antimicrobial
      peptides in the intracellular milieu. On the other hand, evidence that deletion
      of rfaH, as well as some other genes involved in LPS biosynthesis, results in
      enhanced invasion of various mammalian cells is shown. Exposure of common minor
      antigens in the absence of serovar-specific antigens might be responsible for the
      observed cross-reactive nature of the elicited immune response upon vaccination.
      Increased invasiveness of the Salmonella rfaH mutant into antigen-presenting
      cells, combined with increased intracellular killing and the potential for
      raising a cross-protective immune response, renders the rfaH mutant an ideal
      vaccine candidate.

PMID- 16988272
TI  - Infection with Syphacia obvelata (pinworm) induces protective Th2 immune
      responses and influences ovalbumin-induced allergic reactions.
AB  - Infections with pinworms are common in rodent animal facilities. In this study,
      we show the consequence of an outbreak in a transgenic barrier facility of
      infection by Syphacia obvelata, a murine pinworm gastrointestinal nematode.
      Immune responses were defined in experimental infection studies with BALB/c mice.
      Infection with S. obvelata induced a transient Th2-type immune response with
      elevated interleukin 4 (IL-4), IL-5, and IL-13 cytokine production and parasite
      specific immunoglobulin G1 (IgG1). In contrast, BALB/c mice deficient in IL-13,
      IL-4/13, or the IL-4 receptor alpha chain showed chronic disease, with a >100
      fold higher parasite burden, increased gamma interferon production, parasite
      specific IgG2b, and a default Th2 response. Interestingly, infected IL-4-/-
      BALB/c mice showed only slightly elevated parasite burdens compared to the
      control mice, suggesting that IL-13 plays the dominant role in the control of S.
      obvelata. The influence that pinworm infection has on the allergic response to a
      dietary antigen was found to be important. Helminth-infected mice immunized
      against ovalbumin (Ova) elicited more severe anaphylactic shock with reduced Ova
      specific IL-4 and IL-5 than did noninfected controls, demonstrating that S.
      obvelata infection is able to influence nonrelated laboratory experiments. The
      latter outcome highlights the importance of maintaining mice for use as
      experimental models under pinworm-free conditions.

PMID- 16988273
TI  - A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondin
      related adhesion protein but not circumsporozoite protein partially protects
      healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge.
AB  - The safety, immunogenicity, and efficacy of DNA and modified vaccinia virus
      Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin
      related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or
      the circumsporozoite protein (CS) of Plasmodium falciparum. Sixteen healthy
      subjects who never had malaria (malaria-naive subjects) received two priming
      vaccinations with DNA, followed by one boosting immunization with MVA, with
      either ME-TRAP or CS as the antigen. Immunogenicity was assessed by ex vivo gamma
      interferon (IFN-gamma) enzyme-linked immunospot assay (ELISPOT) and antibody
      assay. Two weeks after the final vaccination, the subjects underwent P.
      falciparum sporozoite challenge, with six unvaccinated controls. The vaccines
      were well tolerated and immunogenic, with the DDM-ME TRAP regimen producing
      stronger ex vivo IFN-gamma ELISPOT responses than DDM-CS. One of eight subjects
      receiving the DDM-ME TRAP regimen was completely protected against malaria
      challenge, with this group as a whole showing significant delay to parasitemia
      compared to controls (P = 0.045). The peak ex vivo IFN-gamma ELISPOT response in
      this group correlated strongly with the number of days to parasitemia (P =
      0.033). No protection was observed in the DDM-CS group. Prime-boost vaccination
      with DNA and MVA encoding ME-TRAP but not CS resulted in partial protection
      against P. falciparum sporozoite challenge in the present study.

PMID- 16988274
TI  - Cytokine and chemokine transcription profile during Mycoplasma pulmonis infection
      in susceptible and resistant strains of mice: macrophage inflammatory protein
      1beta (CCL4) and monocyte chemoattractant protein 2 (CCL8) and accumulation of
      CCR5+ Th cells.
AB  - The progression of murine mycoplasma pneumonia is dependent on T cells and other
      immune cells. The role of cytokines in immunity are complex, and identifying the
      network of cytokines produced after infection of mice is essential in dissecting
      the key cytokine cascades involved mycoplasma disease pathogenesis. In the
      present study, mRNA expression of 143 different cytokines, chemokines, or
      receptors were evaluated in lung tissues from both susceptible (BALB/c and
      C3H/HeN) and resistant (C57BL/6) mice after Mycoplasma pulmonis infection. To
      accomplish this, membrane-based cDNA microarrays were used to monitor changes
      mRNA expression in lungs. There was a clear association with disease
      susceptibility and development of cytokine mRNA expression. In addition to
      proinflammatory cytokines, mRNA expression of an anti-inflammatory cytokine,
      interleukin-10, increased with disease severity, suggesting an attempt to
      moderate the severity of the inflammatory response. Furthermore, it is clear that
      an array of chemokines produced in susceptible mice could contribute to the
      recruitment and maintenance of inflammatory cells at the site of disease. In
      support of this, there was an increase in macrophage inflammatory protein 1beta
      (MIP-1beta; CCL4) and monocyte chemoattractant protein 2 (MCP-2; CCL8) mRNA
      levels from mycoplasma-infected mice and a corresponding accumulation of CD4+ Th
      cells expressing the MIP-1beta/MCP-2 receptor, CCR5, in the lungs of mice.
      Furthermore, MIP-1beta- and MCP-2-producing cells and CD4+ T cells were found to
      be in close association in pulmonary lesions. Thus, there was a significant
      cytokine response associated with disease pathogenesis, and these studies provide
      important leads and insights into ongoing cytokine- and chemokine-mediated
      processes in this persistent inflammatory disease.

PMID- 16988275
TI  - Immunogenicity of Duffy binding-like domains that bind chondroitin sulfate A and
      protection against pregnancy-associated malaria.
AB  - Sequestration of Plasmodium falciparum-infected erythrocytes in the placenta is
      implicated in pathological outcomes of pregnancy-associated malaria (PAM). P.
      falciparum isolates that sequester in the placenta primarily bind chondroitin
      sulfate A (CSA). Following exposure to malaria during pregnancy, women in areas
      of endemicity develop immunity, and so multigravid women are less susceptible to
      PAM than primigravidae. Protective immunity to PAM is associated with the
      development of antibodies that recognize diverse CSA-binding, placental P.
      falciparum isolates. The epitopes recognized by such protective antibodies have
      not been identified but are likely to lie in conserved Duffy binding-like (DBL)
      domains, encoded by var genes, that bind CSA. Immunization of mice with the CSA
      binding DBL3gamma domain encoded by var1CSA elicits cross-reactive antibodies
      that recognize diverse CSA-binding P. falciparum isolates and block their binding
      to placental cryosections under flow. However, CSA-binding isolates primarily
      express var2CSA, which does not encode any DBLgamma domains. Here, we demonstrate
      that antibodies raised against DBL3gamma encoded by var1CSA cross-react with one
      of the CSA-binding domains, DBL3X, encoded by var2CSA. This explains the
      paradoxical observation made here and earlier that anti-rDBL3gamma sera recognize
      CSA-binding isolates and provides evidence for the presence of conserved, cross
      reactive epitopes in diverse CSA-binding DBL domains. Such cross-reactive
      epitopes within CSA-binding DBL domains can form the basis for a vaccine that
      provides protection against PAM.

PMID- 16988276
TI  - OspF and OspC1 are Shigella flexneri type III secretion system effectors that are
      required for postinvasion aspects of virulence.
AB  - Shigella flexneri is the causative agent of dysentery, and its pathogenesis is
      mediated by a type III secretion system (T3SS). S. flexneri secretes effector
      proteins into the eukaryotic cell via the T3SS, and these proteins usurp host
      cellular functions to the benefit of the bacteria. OspF and OspC1 are known to be
      secreted by S. flexneri, but their functions are unknown. We transformed S.
      flexneri with a plasmid that expresses a two-hemagglutinin tag (2HA) in frame
      with OspF or OspC1 and verified that these proteins are secreted in a T3SS
      dependent manner. Immunofluorescence of HeLa cells infected with S. flexneri
      expressing OspF-2HA or OspC1-2HA revealed that both proteins localize in the
      nucleus and cytoplasm of host cells. To elucidate the function of these T3SS
      effectors, we constructed DeltaospF and DeltaospC1 deletion mutants by allelic
      exchange. We found that DeltaospF and DeltaospC1 mutants invade host cells and
      form plaques in confluent monolayers similar to wild-type S. flexneri. However,
      in the polymorphonuclear (PMN) cell migration assay, a decrease in neutrophil
      migration was observed for both mutants in comparison to the migration of wild
      type bacteria. Moreover, infection of polarized T84 intestinal cells infected
      with DeltaospF and DeltaospC1 mutants resulted in decreased phosphorylation of
      extracellular signal-regulated kinase 1/2 in comparison to that of T84 cells
      infected with wild-type S. flexneri. To date, these are the first examples of
      T3SS effectors implicated in mitogen-activated protein kinase
      kinase/extracellular signal-regulated kinase pathway activation. Ultimately, OspF
      and OspC1 are essential for PMN transepithelial migration, a phenotype associated
      with increased inflammation and bacterial access to the submucosa, which are
      fundamental aspects of S. flexneri pathogenesis.

PMID- 16988277
TI  - The cryptococcal enzyme inositol phosphosphingolipid-phospholipase C confers
      resistance to the antifungal effects of macrophages and promotes fungal
      dissemination to the central nervous system.
AB  - In recent years, sphingolipids have emerged as critical molecules in the
      regulation of microbial pathogenesis. In fungi, the synthesis of complex
      sphingolipids is important for the regulation of pathogenicity, but the role of
      sphingolipid degradation in fungal virulence is not known. Here, we isolated and
      characterized the inositol phosphosphingolipid-phospholipase C1 (ISC1) gene from
      the fungal pathogen Cryptococcus neoformans and showed that it encodes an enzyme
      that metabolizes fungal inositol sphingolipids. Isc1 protects C. neoformans from
      acidic, oxidative, and nitrosative stresses, which are encountered by the fungus
      in the phagolysosomes of activated macrophages, through a Pma1-dependent
      mechanism(s). In an immunocompetent mouse model, the C. neoformans Deltaisc1
      mutant strain is almost exclusively found extracellularly and in a
      hyperencapsulated form, and its dissemination to the brain is remarkably reduced
      compared to that of control strains. Interestingly, the dissemination of the C.
      neoformans Deltaisc1 strain to the brain is promptly restored in these mice when
      alveolar macrophages are pharmacologically depleted or when infecting an
      immunodeficient mouse in which macrophages are not efficiently activated. These
      studies suggest that Isc1 plays a key role in protecting C. neoformans from the
      intracellular environment of macrophages, whose activation is important for
      preventing fungal dissemination of the Deltaisc1 strain to the central nervous
      system and the development of meningoencephalitis.

PMID- 16988279
TI  - Overexpression, purification, characterization, and pathogenicity of Vibrio
      harveyi hemolysin VHH.
AB  - Vibrio harveyi VHH hemolysin is a putative pathogenicity factor in fish. In this
      study, the hemolysin gene vhhA was overexpressed in Escherichia coli, and the
      purified VHH was characterized with regard to pH and temperature profiles,
      phospholipase activity, cytotoxicity, pathogenicity to flounder, and the signal
      peptide.

PMID- 16988278
TI  - Escherichia coli prevents phagocytosis-induced death of macrophages via classical
      NF-kappaB signaling, a link to T-cell activation.
AB  - NF-kappaB is a crucial mediator of macrophage inflammatory responses, but its
      role in the context of pathogen-induced adaptive immune responses has yet to be
      elucidated. Here, we demonstrate that classical NF-kappaB activation delays
      phagocytosis-induced cell death (PICD) in Raw 264.7 and bone marrow-derived
      macrophages (BMDMs) upon ingestion of bacteria from the Escherichia coli
      laboratory strain Top10. By expression of a nondegradable form of IkappaBalpha
      (superrepressor) and pyrrolidine dithiocarbamate treatment, prolonged activation
      of NF-kappaB upon bacterial coculture is suppressed, whereas initial induction is
      only partially inhibited. This activation pattern results in partial inhibition
      of cellular activation and reduced expression of costimulatory CD86. Notably,
      suppression of classical NF-kappaB activation does not influence bacterial uptake
      rates but is followed by increased production of oxygen radicals and enhanced
      intracellular killing in Raw macrophages. This is associated with reduced
      expression of NF-kappaB-dependent antiapoptotic c-IAP-2 and a loss of the
      mitochondrial transmembrane potential. Accordingly, NF-kappaB inhibition in Raw
      cells and BMDMs causes increased apoptotic rates within 12 h of bacterial
      ingestion. Interestingly, accelerated eradication of E. coli in NF-kappaB
      inhibited macrophages is associated with reduced antigen-specific T-cell
      activation in macrophage-lymphocyte cocultures. These data suggest that E. coli
      inhibits PICD of macrophages via classical, antiapoptotic NF-kappaB activation
      and thus facilitates signaling to T cells. Subsequently, a proper adaptive immune
      response is likely to be generated. Conclusively, therapeutic inhibition of
      classical NF-kappaB activation in macrophages may hamper the initiation of
      adaptive immunity.

PMID- 16988280
TI  - Application of mutated Clostridium difficile toxin A for determination of
      glucosyltransferase-dependent effects.
AB  - Mutation of tryptophan-101 in Clostridium difficile toxin A, a 308-kDa
      glucosyltransferase, resulted in a 50-fold-reduced cytopathic activity in cell
      culture experiments. The mutant toxin A was characterized and applied to
      distinguish between glucosyltransferase-dependent and -independent effects with
      respect to RhoB up-regulation as a cellular stress response.

PMID- 16988281
TI  - Porphyromonas gingivalis minor fimbriae are required for cell-cell interactions.
AB  - Two distinctive types of fimbriae have been identified in Porphyromonas
      gingivalis. In this report, we demonstrate that minor fimbriae are involved in P.
      gingivalis autoaggregation and colonization. A mutant with a deficiency in minor
      fimbriae can bind to a saliva-coated surface but does not form microcolonies as
      the wild-type strain does.

PMID- 16988283
TI  - Sharpen your prognostic acumen: try the destiny dozen.

PMID- 16988282
TI  - Acute systemic immune activation following conjunctival exposure to
      staphylococcal enterotoxin B.
AB  - Conjunctival exposure to the Staphylococcus aureus superantigen staphylococcal
      enterotoxin B (SEB) may occur accidentally, as a result of bioterrorism, or
      during colonization or infection of the external eye. Using human leukocyte
      antigen class II transgenic mice, we show for the first time that conjunctival
      exposure to SEB can cause robust systemic immune activation.

PMID- 16988284
TI  - Mapping ventricular tachycardia.

PMID- 16988286
TI  - Paraplegia after coronary artery bypass graft surgery: case report of a rare
      event.

PMID- 16988285
TI  - Cardiac surgery in elderly patients: strategies to optimize outcomes.

PMID- 16988287
TI  - Critical care nurses' work environments: a baseline status report.

PMID- 16988288
TI  - The patient-family advisory council: keeping a pulse on our customers.

PMID- 16988289
TI  - Ask the experts. Basing vasoactive drips on body weight for bariatric patients.

PMID- 16988290
TI  - Memory aide to reduce the incidence of ventilator-associated pneumonia.

PMID- 16988291
TI  - Acute appendagitis: emergency presentation and computed tomographic appearances.

PMID- 16988292
TI  - Traumatic diaphragmatic herniation presenting as a delayed tension
      faecopneumothorax.
AB  - This article reports an unusual case of delayed presentation of a tension
      faecopneumothorax after traumatic injury to the diaphragm 5 years previously.
      Three important clinical lessons are highlighted: (a) for suspected tension
      pneumothorax, if a considerable quantity of serous fluid is drained in addition
      to air, a communication with the peritoneal cavity should be considered; (b)
      spontaneous tension pneumothorax is an extremely rare condition and other causes
      should be kept in mind; and (c) in the presence of a tension pneumothorax and
      diaphragmatic hernia, the contents of the visceral sac may be completely reduced
      and the hernia may be masked.

PMID- 16988293
TI  - Jejunal transection after blunt abdominal trauma: a report of two cases.

PMID- 16988294
TI  - A novel method of intravascular temperature modulation to treat severe
      hypothermia.
AB  - Intravascular rewarming may provide an efficient and reliable method of restoring
      normal body core temperature in patients, while avoiding after-drop. The system
      provides continuous temperature monitoring and automatically adjusts warm saline
      delivery until the desired temperature is reached.

PMID- 16988295
TI  - Angiokeratoma of the scrotum: a case of scrotal bleeding.
AB  - A 26-year-old man presented to the emergency department after a spontaneous 30
      min bleed from his scrotal skin. He showed no other symptoms and denied any past
      medical history. He was exclusively sexually active, systemically well and
      haemodynamically stable. There were numerous (>50) 1-2 mm dark red, erythematous
      papules over the scrotum, sparing the shaft of penis, inner thigh and abdomen. A
      small area of blood marked the bleeding spot as a single papule. A diagnosis of
      angiokeratoma of the scrotum (Fordyce) was made and potential precipitants such
      as intra-abdominal masses, urinary tract tumours, varicoceles, hernias and
      angiokeratoma corporis diffusum (Fabry syndrome) were excluded. He was discharged
      with dermatology follow-up with a view to local laser treatment. The important
      differential diagnoses are angiokeratoma corporis diffusum and malignant melanoma
      (nodular type). In females, Fordyce angiokeratoma are distributed on labia
      majora.

PMID- 16988296
TI  - Modernising medical careers; the really hard work now begins.

PMID- 16988297
TI  - ABC to <C>ABC: redefining the military trauma paradigm.

PMID- 16988298
TI  - Role of thrombolytic agents in cardiac arrest.
AB  - The prognosis of patients having a cardiac arrest is generally poor, with a few
      exceptions. Interventions that aim to improve outcome in cardiac arrest have
      proved to be disappointing. In particular, no drug has been reliably proved to
      increase survival to discharge after cardiac arrest. Given that coronary
      thrombosis in situ and pulmonary thromboembolism are implicated in a large
      proportion of patients with cardiac arrest, the use of thrombolytic agents has
      been suggested. Case reports and animal studies have shown favourable results,
      and have proposed plausible mechanisms to explain them. This is a review of the
      current literature focusing on the use of thrombolysis during cardiac arrest. A
      comprehensive literature search was carried out on Medline from 1966 to January
      2006, Embase from 1988 to January 2006 and the Cochrane Library, using the Ovid
      interface. Six articles were selected for review. Although some results are
      encouraging, all the studies currently available are limited by size and flaws in
      design.

PMID- 16988299
TI  - Safe discharge: an irrational, unhelpful and unachievable concept.
AB  - Emergency doctors often decide whether to advise hospital admission or discharge
      by assessing whether a decision to discharge home is considered safe. This
      implies that hospital admission may be recommended on the basis of exceeding an
      arbitrarily defined risk of adverse outcome, rather than weighing the potential
      benefits, risks and costs of hospital admission. This approach is likely to lead
      to irrational decision making, unnecessary hospitalisation and unrealistic
      expectations regarding risk. Instead of using the concept of a safe discharge, we
      should take a more rational approach to decision making, weighing the benefits,
      risks and costs of hospitalisation against a default option of discharge home.
      Hospital admission should be recommended only if the expected benefits outweigh
      the risks and can be accrued at an acceptable cost. Guidelines should be
      developed using this approach and used to promote and support rational decision
      making.

PMID- 16988300
TI  - "Here's egg in your eye": a prospective study of blunt ocular trauma resulting
      from thrown eggs.
AB  - OBJECTIVE: To see if a public awareness campaign might be justified around
      Halloween with regard to the dangers of egg throwing. METHOD: A prospective study
      was carried out of all patients who attended the St Paul's Eye Unit's Primary
      Care Department with ocular injuries resulting from a thrown egg over a 14-month
      period from November 2004. All injuries were classified as minor, intermediate or
      major and patients were followed up until discharge. RESULTS: 13 ocular injuries
      that were attributed to assault with a raw egg were reported. In all the 13
      cases, the eggs had been thrown by strangers. 12 of the patients were men and the
      average age of the victims was 27.9 years. 9 patients were injured in the left
      eye and there were no bilateral injuries. On presentation, only 1 patient had a
      visual acuity of 6/6, 7 presented at 6/9, with the remainder having 6/18 or
      worse. All the patients had closed globe injuries. 8 injuries were classified as
      major injuries. 4 patients had permanent sequelae, with one suffering permanent,
      severe visual loss. CONCLUSIONS: Although most of our patients showed improvement
      in visual acuity, there were severe injuries, with the potential for severe
      ocular morbidity. We conclude that there is sufficient injury caused by this
      prank to warrant a public health message. At the least this practice should not
      be promoted by the press.

PMID- 16988301
TI  - A study of depression and anxiety among doctors working in emergency units in
      Denizli, Turkey.
AB  - BACKGROUND: Major work has been carried out on the psychological well-being of
      emergency room doctors in the US, Canada and in other developed countries, but
      little has been published regarding the same in the countries in economic
      transition. OBJECTIVE: To determine the level of, and the factors related to,
      depression and anxiety among doctors working in emergency units in Denizli,
      Turkey. METHODS: This cross-sectional study was conducted in May 2004, using a
      sample of 192 doctors employed in emergency units in Pamukkale University
      Hospital, the City Hospital, the Social Security Hospital, private hospitals,
      citywide primary healthcare centres and 112 emergency services in Denizli,
      Turkey. Data were obtained using a self-administered questionnaire, including
      questions on sociodemographic characteristics and two instruments determining the
      level of depressive symptoms and anxiety. Logistic regression was the method
      chosen for multivariate statistical analysis. RESULTS: The mean (standard
      deviation (SD)) depression score was 10.6 (6.5) and the frequency (%) of
      depression was 29 (15.1). Not having any hobby and having high anxiety scores
      were salient factors among doctors experiencing depressive symptomatology in
      bivariate comparisons. Logistic regression analysis showed that not having any
      hobby (p = 0.07) and having increased anxiety scores (p<0.001) were positive
      contributors to depression scores. The mean (SD) anxiety score was 8.7 (8.2) and
      the frequency (%) of anxiety was 28 (14.6). Being a woman, having a low monthly
      income and having high depression scores contributed considerably to the anxiety
      of doctors in bivariate comparisons. Low monthly income (<1000 v 1000-2000 YTL)
      (p = 0.03), the number of years spent in emergency units (p = 0.03) and having
      high depression scores (p<0.001) were the factors that contributed significantly
      to the anxiety of doctors in the multivariate regression analysis. CONCLUSION:
      The considerable amount of depression and anxiety found among doctors in this
      study should trigger further work. Studies using more powerful designs would help
      to illuminate the factors leading to depression and anxiety, which result in
      attrition among doctors from emergency units.

PMID- 16988302
TI  - The PRIMA study: presentation ischaemia-modified albumin in the emergency
      department.
AB  - OBJECTIVES: To investigate the diagnostic accuracy of presentation ischaemia
      modified albumin (IMA), in addition to cardiac troponin I (TnI), as a strategy to
      rapidly ascribe low risk to patients with chest pain attending an emergency
      department, and to determine whether IMA has the potential to reduce transit time
      in emergency departments. METHODS: A prospective observational study was carried
      out in two emergency departments (belonging to the John Radcliffe Hospital,
      Oxford, UK; and the Frenchay Hospital, Bristol, UK) of similar size. Consecutive
      adult patients presenting with features of possible ischaemic cardiac chest pain
      and a normal electrocardiogram were eligible. The index test (measurement of IMA
      and TnI at presentation) and reference standard (delayed TnI measurement, taken
      at least 8 h after pain onset) were applied to all recruited patients. All
      clinicians were blinded to the results of the index test. Assays were carried out
      in a single laboratory using standard techniques. RESULTS: 399 patients were
      recruited; 277 patients had a result for both the index test and reference
      standard. The sensitivity was 97.6% (95% confidence interval (CI) 87.4 to 99.9),
      negative predictive value 97% (95% CI 84.2 to 99.9) and specificity 13.6% (95% CI
      9.5 to 18.7). Sensitivity analysis showed similar findings in three alternative
      scenarios. Receiver operating characteristic analysis indicated that a different
      "cut-off" value for IMA would not improve the properties of the test. The median
      potential time saved (n = 268) was 6 h and 10 min. CONCLUSION: The diagnostic
      accuracy of presentation IMA in this study does not support its use as an
      effective risk stratification tool for patients with chest pain in the emergency
      department. The sensitivity is insufficiently high, with a small number of false
      negatives undermining the safety of the test. Frequent false positives produce a
      low specificity that limits the practical value of the test.

PMID- 16988303
TI  - Qualitative evaluation of a formal bedside clinical teaching programme in an
      emergency department.
AB  - BACKGROUND: Bedside clinical teaching in emergency departments is usually
      opportunist or ad hoc. A structured bedside clinical teaching programme was
      implemented, where a consultant and registrar were formally allocated to teaching
      and learning roles separated from the usual departmental management or clinical
      roles. Themes emphasised included clinical reasoning, practical clinical
      knowledge, communication, physical examination, procedural and professional
      skills. AIM: To evaluate the perceived educational value, effects on patient care
      and areas for ongoing development. METHODS: The study setting was an urban,
      tertiary referral, university-affiliated emergency department with prospectively
      allocated educational shifts of 4 or 5 h duration over a 6-month period.
      Evaluation was by session and course evaluation questionnaires, with respondents
      ranking predetermined themes and giving free-text responses. Qualitative
      presentation of results allowed exploration of the themes identified. RESULTS:
      Learners ranked history taking and physical examination technique as the most
      frequently learnt item, but clinical reasoning as the most important theme
      learnt. Informal discussion and performance critique or constructive feedback
      were the most frequent teaching methods. The biggest obstacle to learning was
      learner apprehension. The most frequent positive effect on patient care was
      faster management, decision making or disposition. Most often, no negative effect
      on patient care was identified. CONCLUSION: Formal bedside teaching is effective
      if organised with adequate staffing to quarantine the teacher and learner from
      routine clinical duties, and concentrating on themes best taught in the patient
      setting. Clinical reasoning and clinical knowledge were perceived to be most
      important, with positive effects on patient care through more thorough assessment
      and faster decision making.

PMID- 16988304
TI  - Children presenting to hospital with acute alcohol intoxication.
AB  - AIMS: To investigate the problem of children presenting to hospital with alcohol
      intoxication. METHODS: An observational study was conducted over 18 months
      profiling children who presented to hospital with acute alcohol intoxication,
      proved by laboratory tests on blood alcohol levels (BALs). The study was part of
      a multicentre-funded injury prevention project based on the widely accepted
      Canadian Hospital Injury Reporting and Prevention Programme. RESULTS: 62 children
      (31 boys), mean age 14.5 years, presented with alcohol intoxication proved by
      BALs. The mean BAL was 203 mg/dl (standard deviation (SD) 80.7). As a point of
      reference, 56 (90%) children had BAL above the UK legal driving limit of 80
      mg/dl. The most common type of alcohol consumed was spirits, in the form of
      whisky, gin, vodka and tequila. No significant association was seen between age
      and BAL. Children with high alcohol levels were much more likely to have lower
      Glasgow Coma Scores (p<0.001), but in contrast with conventional teaching, there
      was no association between blood glucose levels and BALs. The median Glasgow Coma
      Score on admission to the emergency department was 12. 15 (24%) children had a
      score < or = 8/15. Injuries were present in 21 (34%) children, most of which were
      minor injuries. Minor head injury was most common, accounting for 42% of the
      injuries. The most common cause of injury was a fall. DISCUSSION: The results of
      this study confirm the heavy use of alcohol by some young children. This
      highlights a definite problem, which needs to be dealt with by a variety of
      measures, giving particular consideration to the ease of access to alcohol by
      children.

PMID- 16988305
TI  - Deep vein thrombosis among injecting drug users in Sheffield.
AB  - AIMS: To identify the proportion of patients testing positive for deep vein
      thrombosis (DVT) who are injecting drug users (IDUs), and examine differences in
      the investigation and management of this group compared with non-IDUs. METHODS:
      Analysis of data collected from emergency department records and a review of
      patient notes. RESULTS: All patients in this study who were known to inject
      recreational drugs tested positive for DVT on Doppler ultrasound scan.
      CONCLUSIONS: IDUs should be considered at high risk of developing DVT and should
      be investigated accordingly.

PMID- 16988306
TI  - Estimating the rate of re-expansion of spontaneous pneumothorax by a formula
      derived from computed tomography volumetry studies.
AB  - BACKGROUND: Available evidence suggesting that the rate of re-expansion of
      spontaneous pneumothorax is 1.25%/day is based on a small sample and mathematical
      modelling-based estimates. AIM: To estimate the rate of re-expansion of
      spontaneous pneumothoraces by a formula derived from computed tomography
      volumetry studies. METHODS: This retrospective study included adult patients with
      spontaneous pneumothorax, identified from patient management databases, who were
      treated conservatively. Medical records were reviewed to confirm that no
      intervention such as aspiration or catheter drainage had occurred. Radiographs
      were reviewed independently by two researchers and measured according to the
      method described by Collins et al. Their formula was used to estimate
      pneumothorax size on each date. The rate of re-expansion was defined as the
      change in size (%)/number of days between radiographs. Patients were excluded if
      they did not have at least two radiographs taken, at least 1 day apart. Data were
      analysed using cluster analysis by patient to minimise the effect of repeated
      measures from an individual patient. RESULTS: 88 episodes were identified in 57
      patients. 82% were men and the patients had a median age of 22 years. The average
      rate of re-expansion was 2.2%/day (95% confidence interval 1.4% to 3.0%), but
      varied between -7.5% and 13.4%/day. CONCLUSION: Spontaneous pneumothoraces
      treated conservatively re-expand at an average rate of 2.2%/day.

PMID- 16988307
TI  - Exploring the clinical utility of blood ketone levels in the emergency department
      assessment of paediatric patients.
AB  - BACKGROUND: Ketonuria (on standard urine testing) is a frequent finding in
      children presenting to emergency departments. With the advent of hand-held ketone
      meters, blood ketone levels can now be rapidly quantified. HYPOTHESIS: Point of
      care testing (POCT) of blood ketone levels could provide clinically useful
      information on severity of illness in children and risk of hospital admission.
      METHODS: A prospective study using POCT of blood ketone levels in a convenience
      sample of children <13 years old, with a typical case mix of medical problems.
      FINDINGS: 186 children were studied. The range of ketone levels varied widely
      among this study population depending on the presenting complaint. Higher levels
      were noted in those presenting with anorexia or vomiting and fever. The median
      ketone level of the total study population was 0.2 (range 0-6.0, interquartile
      range 0.1-0.9) mmol/l. Ketone levels correlated poorly with discharge destination
      and duration of admission. However, receiver-operator characteristics for ketones
      as a predictor of admission were comparable to Pediatric Risk of Admission scores
      (area under the curve 0.64 and 0.72, respectively) and may represent an
      independent risk factor for admission. A ketone level >1.2 mmol/l has a positive
      predictive value of 66.7% for admission. Ketone levels correlated well with
      decreased oral intake (R2 = 0.25; p<0.001). CONCLUSIONS: A strong association was
      found between ketone levels, decreased oral intake and fever. Although ketone
      levels do not correlate well with more traditional markers of illness severity,
      they can help to predict the requirement for admission to hospital when
      interpreted in the context of the presenting illness. They may have applications
      in both the emergency department and primary care settings. Further prospective
      testing is required to validate these findings.

PMID- 16988308
TI  - The tuning fork test--a useful tool for improving specificity in "Ottawa
      positive" patients after ankle inversion injury.
AB  - The Ottawa ankle rules are a clinical instrument calibrated towards a high
      sensitivity in order not to miss any fractures of the ankle or mid-foot. This is
      at the cost of a mean specificity of around only 32%. The aim of this study was
      to determine the suitability of tuning fork testing in combination with existing
      Ottawa guidance for increasing the specificity in detecting fractures of the
      lateral malleolus. A prospective pilot study was carried out, in which a single
      trained investigator examined all patients with already "Ottawa positive"
      findings for possible lateral malleolus injury by applying a tuning fork (C(o)
      128 Hz). The tuning fork test findings were compared with formal reports of plain
      ankle radiographs using simple cross-table analysis. The observed prevalence of
      ankle fractures was 5 of 49 (10%). Sensitivity and specificity were calculated as
      100% and 61%, respectively, for tuning fork testing on the tip of the lateral
      malleolus (TLM), and as 100% and 95%, respectively, for testing on the distal
      fibula shaft (DFS). The associated positive and negative likelihood ratios were
      2.59 and 0 (TLM), and 22 and 0 (DFS), respectively. The data were significant,
      with p = 0.014 (TLM) and p<0.001 (DFS). This study suggests that additional
      tuning fork testing of "Ottawa positive" patients may lead to a marked reduction
      in ankle radiographs, with consequently reduced radiation exposure and journey
      time. This may be particularly relevant in situations where radiological
      facilities are not readily available (expedition medicine) or where access to
      these has to be prioritised (major incidents, natural catastrophes).

PMID- 16988309
TI  - Delivery of local anaesthetic via a sternal catheter to reduce the pain caused by
      sternal fractures: first case series using the new technique.
AB  - Sternal fractures cause considerable pain, and a proportion of patients require
      admission for analgesia. Local anaesthetic techniques have been used to reduce
      the pain from chest wall injuries and may reduce complications from these
      injuries. The use of a local anaesthetic delivered via a sternal catheter over a
      fractured sternum has been described in a patient whose pain was inadequately
      controlled with opiates. This technique was recently offered to patients in the
      emergency department at the Royal Devon and Exeter Hospital, Exeter, UK, and the
      experiences of patients and doctors are reported. Findings from this first case
      series suggest that the technique seems to be effective, well tolerated and
      acceptable to patients.

PMID- 16988310
TI  - Instructional design and the emergency department.
AB  - This paper studies the effectiveness of different educational programmes. A
      number of cohorts of junior doctors received one of two different induction
      training packages. These programmes differed principally in the length of time
      over which they were administered. The junior doctors were then assessed using a
      structured questionnaire. There was a noticeable difference in the factual recall
      between the cohorts depending on what programme they had attended. Those
      attending the programme delivered over an extended period showed better
      performance on assessment. The interpretations and implications of these findings
      are discussed.

PMID- 16988311
TI  - Diagnosis and management of common maxillofacial injuries in the emergency
      department. Part 1: Advanced trauma life support.
AB  - Maxillofacial injuries are often seen in the emergency department. Fractures of
      the facial skeleton are commonly seen after assault, road traffic accidents,
      falls, and sporting injuries in a ratio mandibular:zygoma:maxillary of 6:2:1.
      Clinicians must be familiar with their management so that appropriate treatment
      may be used.

PMID- 16988312
TI  - Trends and the future of postgraduate medical education.
AB  - Where is the present flurry of activity in medical education leading and what
      sort of future is envisaged? This paper looks at trends in postgraduate medical
      education. Four themes and two trends for each theme have been identified. The
      themes are: the postgraduate medical curriculum, the application of learning
      technologies, assessment of competence, and professionalism in medical education.
      The trends are: outcome based education and a unitary approach to medical
      education; the use of simulators and e-learning; competency and performance based
      assessment, and portfolios and self assessment; and training the trainer and best
      evidence medical education. Any limitations in implementing change will likely
      result from a lack of imagination in those planning postgraduate medical
      education and their ability to bring about the necessary changes. To avoid a
      growing gap developing between what is possible educationally and what is
      delivered, it is clear that we need a new paradigm for postgraduate medical
      education.

PMID- 16988313
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Accuracy of emergency department ultrasound scanning in detecting
      abdominal aortic aneurysm.
AB  - A short-cut review was carried out to establish whether emergency department
      ultrasound scanning had clinical utility for the diagnosis of abdominal aortic
      aneurysm (AAA). A total of 73 papers were found using the reported searches, of
      which 4 presented the best evidence to answer the clinical question. The author,
      date and country of publication, patient group studied, study type, relevant
      outcomes, results and study weaknesses of these best papers are tabulated. It is
      concluded that in patients suspected of having AAA, emergency department bedside
      ultrasound scanning for AAA is sensitive and specific and may improve patient
      care.

PMID- 16988315
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Use of aspirin in acute stroke.
AB  - A short-cut review was carried out to establish whether the administration of
      aspirin before computed tomography scanning improved outcome in patients with
      symptoms suggestive of stroke. In all, 866 papers were found using the reported
      searches, two of which presented the best evidence to answer the clinical
      question. The author group, date and country of publication, patient group
      studied, study type, relevant outcomes, results and study weaknesses of these
      best papers are tabulated. If a computed tomography scan is to be carried out
      within 48 h of onset of symptoms, then it is prudent to await the result before
      starting aspirin.

PMID- 16988316
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Myringotomy in traumatic haemotympanum.
AB  - A short-cut review was carried out to establish whether myringotomy is of value
      in cases of haemotympanum. In all, 205 papers were found in Medline and 105 in
      Cochrane using the reported searches. None presented any evidence to answer the
      clinical question. Hence, it is concluded that there is no evidence available to
      guide this decision and that local expert advice should be followed.

PMID- 16988317
TI  - Results of streamlined regional ambulance transport and subsequent treatment of
      acute abdominal aortic aneurysms.
AB  - OBJECTIVE: To describe the triage of patients operated for non-ruptured and
      ruptured abdominal aortic aneurysms (AAAs) before the endovascular era. DESIGN:
      Retrospective single-centre cohort study. METHODS: All patients treated for an
      acute AAA between 1998 and 2001 and admitted to our hospital were evaluated in
      the emergency department for urgent AAA surgery. All time intervals, from the
      telephone call from the patient to the ambulance department, to the arrival of
      the patient in the operating theatre, were analysed. Intraoperative, hospital and
      1-year survival were determined. RESULTS: 160 patients with an acute AAA were
      transported to our hospital. Mean (SD) age was 71 (8) years, and 138 (86%) were
      men. 34 (21%) of these patients had symptomatic, non-ruptured AAA (sAAA) and 126
      patients had ruptured AAA (rAAA). All patients with sAAA and 98% of patients with
      rAAA were operated upon. For the patients with rAAA, median time from telephone
      call to arrival at the hospital was 43 min (interquartile range 33-53 min) and
      median time from arrival at the hospital to arrival at the operating room was 25
      min (interquartile range 11-50 min). Intraoperative mortality was 0% for sAAA and
      11% for rAAA (p = 0.042), and hospital mortality was 12% and 33%, respectively (p
      = 0.014). CONCLUSIONS: A multidisciplinary unified strategy resulted in a rapid
      throughput of patients with acute AAA. Rapid transport, diagnosis and surgery
      resulted in favourable hospital mortality. Despite the fact that nearly all the
      patients were operated upon, survival was favourable compared with published
      data.

PMID- 16988318
TI  - Ambulance alerting to hospital: the need for clearer guidance.
AB  - BACKGROUND: The decision by paramedics to alert a receiving hospital to the
      imminent arrival of a critically ill patient is currently based on the crew's
      clinical judgement. AIMS: To evaluate the efficiency of current alerting practice
      and to assess the need for objective guidelines. METHODS: Data were collected in
      the Birmingham Heartlands Hospital, Birmingham, UK, over 1 week in February 2005.
      All alerted patients and all critically ill patients brought to the emergency
      department over this time period were identified. These two groups were studied
      to find those patients who were alerted but not critically ill, those who were
      critically ill but not alerted, and those who were both alerted and critically
      ill. The presenting conditions were identified and compared between groups.
      RESULTS: 454 patients were brought by ambulance to the emergency department
      during the study week. Of the 27 alerted patients, 23 were critically ill,
      leaving four patients alerted inappropriately. 29 of the 52 critically ill
      patients had not been alerted by ambulance crews. Most (n = 22) of these patients
      were adults with medical conditions. CONCLUSIONS: Ambulance crews do not alert
      hospitals to critically ill patients adequately. The Modified Early Warning Score
      should be considered to be the basis of a prehospital tool to aid their decision.

PMID- 16988319
TI  - Case of the month: A case of airway obstruction following tenecteplase
      administration.
AB  - The value of thrombolysis in the treatment of acute myocardial infarction is well
      established. Haemorrhage into subcutaneous tissues is fortunately a rare
      complication of fibrinolytic administration. However, if as a result of trauma a
      haematoma develops within the neck following thrombolysis, it can lead to rapid
      airway compromise. This is the first reported case of tenecteplase administration
      leading to subcutaneous haemorrhage and consequent airway compromise. It is also
      the first reported case where the antecedent trauma was a jaw thrust.

PMID- 16988320
TI  - Cocaine induced non-ST-elevation myocardial infarction: an uncommon
      electrocardiographic presentation.

PMID- 16988321
TI  - Localised pneumothorax.

PMID- 16988322
TI  - Unstable proximal interphalangeal joint dislocations: another cause.

PMID- 16988323
TI  - Cryptorchidism and semen quality: a TEM and molecular study.
AB  - Cryptorchidism is a pathological condition defined as the failure of the testis
      to descend into the scrotum, the location of the cryptorchid testis can be in the
      inguinal canal or in the prescrotal and abdominal area, sometimes resulting in
      atrophic seminiferous tubules. The aim of this study was to analyze semen quality
      of men who underwent orchidopexy for unilateral or bilateral cryptorchidism
      during childhood. Semen quality was investigated by light microscopy to evaluate
      sperm concentration and motility. Sperm morphology was performed by transmission
      electron microscope (TEM), and the data were mathematically elaborated. The
      presence of Y microdeletions was investigated by polymerase chain reaction. The
      effect of cryptorchidism on meiosis was explored by fluorescence in situ
      hybridization (FISH). The incidence of azoospermia was higher in the group with
      bilateral compared with unilateral cryptorchidism, and semen parameters were
      better in the unilateral group. Sperm pathologies detected by TEM indicated a
      severe deterioration of sperm quality in both groups. Necrosis and apoptosis
      appeared to be the most frequent pathologies, and their values reached
      statistical significance compared with those from fertile controls. The presence
      of chromosome Y microdeletions in patients with cryptorchidism and severe
      spermatogenetic defects is controversial. No microdeletions were found in this
      study. FISH values indicated that the mean percentage of gonosome disomies and
      diploidies were generally out of normal range, indicating a severe disturbance of
      meiotic segregation. The effects induced by cryptorchidism resolved in childhood
      seem to include a spermatogenetic impairment, leading to recommendation of
      detailed ultrastructural and chromosomal sperm analyses before undertaking
      assisted reproductive techniques.

PMID- 16988324
TI  - Serotonin concentration, synthesis, cell origin, and targets in the rat caput
      epididymis during sexual maturation and variations associated with adult mating
      status: morphological and biochemical studies.
AB  - The caput epididymis of some mammals contains large quantities of serotonin whose
      origin, targets, and physiological variations have been poorly studied. We
      combined morphological and biochemical techniques to begin approaching these
      aspects of serotonin in the rat caput epididymis. Serotonin immunostaining was
      detected in mast, epithelial, and neuroendocrine cells. Epithelial cells
      displayed immunoreactivity to 5HT(1A), 5HT(2A,) and 5HT(3) serotonin receptors.
      Endothelial and mast cells labeled positive for 5HT(1B) serotonin receptors and
      spermatozoa displayed 5HT(2A) and 5HT(3) serotonin receptor immunoreactivity.
      Epithelial, endothelial, and mast cells stained positive for serotonin
      transporters. Only epithelial cells showed tryptophan hydroxylase
      immunoreactivity; this enzyme catalyzes the limiting step in the serotonin
      synthetic pathway. In addition, Western blot analyses of caput homogenates
      documented the presence of 2 protein bands ( approximately 51 kd and
      approximately 48 kd) that were immunoreactive for tryptophan hydroxylase.
      Chromatographic analyses documented the presence of tryptophan hydroxylase in the
      caput, and showed that both its activity and serotonin availability increased
      with sexual maturation and decreased following p-chlorophenylalanine treatment,
      an inhibitor of tryptophan hydroxylase activity. Interestingly, serotonin
      concentration and tryptophan hydroxylase activity tended to be higher in breeding
      males than in those with no mating experience. We think that these results
      support the existence of a local serotoninergic system in the rat caput
      epididymis that might regulate some aspects of male reproductive function.

PMID- 16988325
TI  - Pregnancies in cryptozoospermia with sperm ejaculated one day before ICSI: four
      case reports.

PMID- 16988326
TI  - A stereological analysis of the response of spermatogenesis to an acute
      inflammatory episode in adult rats.
AB  - Male fertility is inhibited by inflammatory disease, but the mechanisms
      responsible are poorly defined. The effects of acute systemic inflammation
      induced by a single IP injection of lipopolysaccharide (LPS) on spermatogenic
      function in adult male rats were investigated using detailed stereological
      analysis. The earliest effect observed was a significant maturational delay of
      meiosis during the leptotene/zygotene phase (at stages IX-XIII) within 24 hours.
      This was followed within 6 days by an increase in premature release of these
      cells and the adjacent, more luminally located generation of round spermatids
      from the seminiferous epithelium. An increase in germ cell apoptosis within
      stages IX-XIII also occurred at this time. These data indicate that the initial
      effects of acute inflammation on the seminiferous epithelium are most pronounced
      on stages IX-XIII. The effects were not consistent with a loss of hormonal
      regulation, suggesting that a direct effect of inflammation on the function of
      the Sertoli cell during this critical stage of meiosis is involved. In the longer
      term, however, the consequences of this acute inflammatory episode were
      relatively minor: within 28 days there had been a compensatory increase in the
      efficiency of the seminiferous epithelium, restoring the spermatogenic capacity
      of the testis towards preinflammation levels.

PMID- 16988327
TI  - Hypogonadism and reduced bone mineral density in heterozygous H63D mutation in
      the HFE gene: an unusual presentation of hereditary hemochromatosis.

PMID- 16988328
TI  - Long-term results of autologous venous grafts for penile morphological
      reconstruction.
AB  - In order to evaluate the long-term results of autologous venous grafts, we
      present an overview of patients who underwent a procedure utilizing a venous
      patch from the deep dorsal vein with or without combination of the cavernosal
      vein in treating penile deformity. From March 1995 to March 2005, a total of 85
      consecutive patients with Peyronie disease or congenital penile deviation
      underwent venous grafting. Tunical corporotomy was covered using transplanted
      venous wall sutured microscopically to collagen bundles of the inner circular and
      outer longitudinal layer of the tunica albuginea. The vein was sutured with the
      serosal side outward, after it had been detubularized, properly constructed, and
      spliced together. In this cohort, 48 patients with Peyronie disease and 37 with
      congenital penile deviation were respectively categorized as belonging to the
      Peyronie and congenital groups. All patients were evaluated preoperatively and
      postoperatively with the International Index of Erectile Function (IIEF-5)
      scoring, angle measurement of erectile penis, satisfaction with the penile shape,
      and a cavernosogram which was further available for 15 patients. Histological
      confirmation in 5 cases was followed up for up to 10 years. The mean angle
      improvement was 44.8 +/- 3.6 degrees for the Peyronie group and 37.6 +/- 3.8
      degrees for the congenital group. A satisfactory penile shape was achieved in 77
      (90.6%) patients, although 8 men (9.4%) complained of mild deviation of the penis
      (<15 degrees). Erectile function was good in 81 patients, although 6 of them had
      to use oral sildenafil/tadalafil postoperatively. Overall, they had a mean
      preoperative IIEF-5 score of 19.7 +/- 2.8, which increased to a mean
      postoperative score of 21.6 +/- 2.2. The cavernosograms consistently disclosed a
      good penile shape. The histological confirmation showed that the donor vein
      retained its histological character despite the fact that perfect coalescence and
      lining up with the tunica albuginea were noted. The autologous vein appears to be
      an acceptable graft material, and the transplanted vein may have a modeling
      action rather than a scaffolding role in venous patch surgery on the penile
      tunica albuginea. Careful microsurgical manipulation is required to achieve a
      satisfactory, sustainable outcome.

PMID- 16988329
TI  - The advancement of pure local anesthesia for penile surgeries: can an outpatient
      basis be sustainable?
AB  - Although topical anesthetic blockage for penile surgeries has been substantially
      reported in the medical literature, its methodology, reliability, and
      reproducibility have not been consistent. We report on several methods of topical
      blocks for local anesthesia in patients with indications for penile surgeries.
      From March 1993 to March 2003, a total of 1131 men, ages 19 to 87, underwent
      penile surgeries in which 165, 203, 708, 45, and 10 patients received penile
      implantation, modified Nesbit procedure, venous surgery, venous patches, and
      arterial revascularization respectively, under pure local anesthesia on an
      outpatient basis. They were categorized into the implant, Nesbit, venous, patch,
      and arterial groups respectively. Proximal dorsal nerve blockage, peripenile
      infiltration, and topical injection, although challenging, were sufficient local
      anesthesia for patients in the last 4 patient groups. A new method of crural
      blockade, however, was also required for optimal anesthesia of the cavernous
      nerve for implantation purposes. The anesthetic effects and postoperative results
      were satisfactory. Common immediate side effects included puncture of the corpus
      spongiosum or the deep dorsal vein as well as the innominate vessel, subcutaneous
      ecchymosis, transient palpitations, and acceptable low level of pain. There were
      no significant late complications. In the implant group, however, 6.1% of
      patients (10/165) had experienced pain over the perineum for 1 to 2 weeks
      postoperatively. Overall there were statistical differences in scoring between
      the 5 groups in which the implant group stood out when a visual analog scale of
      100 mm was used. Topical nerve blockades proved to be reliable, simple, and safe,
      with minimal complications. They offer the advantages of less morbidity, reduced
      effects of anesthesia, protection of privacy, and a rapid return to preoperative
      daily activity.

PMID- 16988330
TI  - Culture and maintenance of Agrobacterium strains.
AB  - As aerobic chemoorganotrophs, most Agrobacterium strains will grow on a wide
      range of complex and defined media. Methods commonly used for the culture and
      storage of other chemoorganotrophs will usually work for agrobacteria as well.
      Problems with culture or strain maintenance will occur more frequently because of
      careless technique than because of strain difficulties. Here we describe a few of
      the complex and defined media that have been successfully used in the growth of
      agrobacteria including some that are semiselective for agrobacteria. Finally, we
      present methods suitable for short- and long-term storage of Agrobacterium
      strains.

PMID- 16988332
TI  - Three methods for the introduction of foreign DNA into Agrobacterium.
AB  - The genetic manipulation of Agrobacterium tumefaciens is used to facilitate
      studies of bacterial gene functions or as a first step in introducing genetic
      material into transformable plant cells through the use of T-DNA binary vectors.
      Three methods are commonly used. Transformation with purified plasmid can be done
      with either electroporation or a simple freeze/thaw transformation method.
      Alternatively, a mobilizable plasmid can be placed into Agrobacterium using the
      triparental mating method. Here we present three detailed protocols for
      Agrobacterium strain construction using electroporation, the freeze/thaw method
      of transformation, and triparental mating.

PMID- 16988331
TI  - Binary vectors and super-binary vectors.
AB  - A binary vector is a standard tool in the transformation of higher plants
      mediated by Agrobacterium tumefaciens. It is composed of the borders of T-DNA,
      multiple cloning sites, replication functions for Escherichia coli and A.
      tumefaciens, selectable marker genes, reporter genes, and other accessory
      elements that can improve the efficiency of and/or give further capability to the
      system. A super-binary vector carries additional virulence genes from a Ti
      plasmid, and exhibits very high frequency of transformation, which is valuable
      for recalcitrant plants such as cereals. A number of useful vectors are widely
      circulated. Whereas vectors with compatible selectable markers and convenient
      cloning sites are usually the top criteria when inserting gene fragments shorter
      than 15 kb, the capability of maintaining a large DNA piece is more important for
      consideration when introducing DNA fragments larger than 15 kb. Because no vector
      is perfect for every project, it is recommended that modification or construction
      of vectors should be made according to the objective of the experiments. Existing
      vectors serve as good sources of components.

PMID- 16988333
TI  - Integration of genes into the chromosome of Agrobacterium tumefaciens C58.
AB  - Agrobacterium tumefaciens has been widely used to transform numerous plant
      species. Frequently, investigators want to place more than one gene into
      Agrobacterium in order to manipulate various bacterial functions during plant
      genetic transformation. These genes are frequently brought into the bacterium by
      multiple plasmids. It is difficult to maintain several plasmids in the same
      bacterium without the use of a variety of antibiotics. However, the use of some
      antibiotics is not feasible for certain Agrobacterium strains. Also, too many
      different antibiotics in the culture medium generally results in slow growth of
      Agrobacterium. Therefore, it is to one's advantage to place genes of interest
      onto the bacterial chromosome to eliminate the use of multiple antibiotics during
      bacterial growth. This chapter describes in detail a method to integrate a gene
      of interest into the pgl/picA locus of the Agrobacterium tumefaciens C58
      chromosome. The integrated gene is stably maintained as single copy per cell
      without the need for selection.

PMID- 16988334
TI  - Nucleic acid extraction from Agrobacterium strains.
AB  - Agrobacterium is routinely used as a tool for moving genetic constructs into
      plant cells. The successful use of Agrobacterium as a tool for the genetic
      engineering of plant cells often requires the manipulation and analysis of
      nucleic acids present in recombinant Agrobacterium strains. Here we present
      dependable methods for the isolation of genomic (total) DNA, mega-plasmid DNA,
      shuttle or binary plasmid DNA, and RNA. In addition, we provide a simple method
      for the electronic transfer of shuttle plasmids from Agrobacterium to E. coli for
      use when their low copy number in Agrobacterium impedes plasmid isolation from
      that strain.

PMID- 16988335
TI  - Agrobacterium virulence gene induction.
AB  - The ability of Agrobacterium to transform plants and other organisms is under
      highly regulated genetic control. Two Virulence (Vir) proteins, VirA and VirG,
      function as a two-component regulatory system to sense particular phenolic
      compounds synthesized by wounded plant tissues. Induction by these phenolic
      compounds, in the presence of certain neutral or acid sugars, results in
      activation of other vir genes, leading to the processing of T-DNA from the Ti
      plasmid and transfer of T-DNA to recipient host cells. Many plant, and most
      nonplant, species do not provide sufficient quantities of the correct phenolic
      compounds to permit efficient Agrobacterium-mediated genetic transformation to
      occur. In order to transform these species, phenolic inducing compounds must be
      added to agrobacteria before and/or during cocultivation of recipient cells with
      the bacteria. This chapter discusses conditions for efficient induction of
      Agrobacterium virulence genes by phenolic compounds.

PMID- 16988336
TI  - Arabidopsis thaliana floral dip transformation method.
AB  - Arabidopsis floral dip transformation is notable for a number of reasons. First,
      it is strikingly simple to perform. Agrobacterium is applied to flowering
      Arabidopsis plants that subsequently set seed, and transgenic plants are then
      selected among the progeny seedlings. Because no plant tissue culture is
      required, somaclonal variation is avoided, and the procedure can be performed
      easily by nonspecialists. Success rates are high: it is common that 1% of the
      progeny seedlings are transgenic. The biology behind the method is interesting:
      Arabidopsis and some related Brassicaceae are apparently unique in allowing
      exogenously applied Agrobacterium to colonize the interior of developing ovaries,
      where female gametophyte cell lineages are transformed. The availability of the
      method has had a transformative effect on the overall practice of plant molecular
      biology, as the generation and analysis of large numbers of transgenic plants is
      now routine in hundreds of laboratories. The method has been exploited in a
      genomics context to make stable gene knockout plant lines for most Arabidopsis
      genes.

PMID- 16988337
TI  - Agrobacterium transformation of Arabidopsis thaliana roots: a quantitative assay.
AB  - Arabidopsis thaliana has become a major model system for investigating plant
      molecular, genetic, and biochemical processes. Arabidopsis is highly susceptible
      to Agrobacterium-mediated transformation using "flower dip" and "vacuum
      infiltration" protocols. However, Arabidopsis has also become a major system to
      investigate the mechanism of Agrobacterium-mediated transformation of somatic
      tissue. Such investigations require a reproducible, quantitative assay system to
      determine transformation frequency. We describe here an Arabidopsis root
      transformation protocol that can be used to determine transformation frequencies
      for wild-type and mutant Agrobacterium strains and for various Arabidopsis wild
      type and mutant lines.

PMID- 16988338
TI  - Medicago truncatula transformation using leaf explants.
AB  - Legumes have long been recalcitrant to efficient Agrobacterium tumefaciens
      mediated transformation. The choice and use of model legume plants (Medicago
      truncatula and Lotus japonicus) for molecular studies has triggered extensive
      studies devoted to the development of efficient Agrobacterium-mediated
      transformation protocols for these two plants. In M. truncatula, transformation
      protocols rely on the use of highly regenerable lines obtained by recurrent in
      vitro culture selection. These protocols are based on Agrobacterium-mediated
      transformation of M. truncatula followed by somatic embryogenesis-mediated plant
      regeneration. We describe here the protocol developed for M. truncatula R108-1
      (c3).

PMID- 16988339
TI  - Medicago truncatula transformation using cotyledon explants.
AB  - Medicago truncatula has been developed into a model species for legumes. Large
      numbers of ESTs have been sequenced, and sequencing of the complete gene-rich
      space of the genotype Jemalong A17 is in progress. By using cotyledons as
      explants for Agrobacterium infection and direct shoot formation, this protocol
      allows for rapid production of transgenic plants from A17 and other genotypes.
      Transgenic plants can be regenerated and established in the greenhouse in only 3
      4 mo after Agrobacterium-mediated transformation. Transformation frequency is in
      the range of 5-12%.

PMID- 16988340
TI  - Medicago truncatula transformation using root explants.
AB  - Medicago truncatula is a forage crop that has been developed into a model legume.
      As a model plant, M. truncatula is particularly useful for the study of root
      endosymbiotic associations, including nodulation and mycorrhizal colonization.
      The development of different transformation methods is an important aspect for
      functional genomic studies in the species. This protocol describes an efficient
      system for generating transgenic plants from M. truncatula roots based on
      Agrobacterium tumefaciens-mediated transformation. Furthermore, the protocol can
      be easily adapted for recovering fertile transgenic plants from transformed hairy
      roots.

PMID- 16988341
TI  - Nicotiana (Nicotiana tobaccum, Nicotiana benthamiana).
AB  - Agrobacterium-mediated transformation of Nicotiana species, namely, Nicotiana
      tobaccum and Nicotiana benthamiana, using leaf disks as the target explant has
      provided the plant community with a valuable tool for rapid evaluation of
      transgenes in higher plants. This protocol has a number of desirable attributes:
      readily available explant material, high efficiency, and a relatively quick
      turnaround time. The in vitro regeneration scheme of the leaf disks is prolific
      and follows an indirect organogenic differentiation. N. tobaccum and N.
      benthamiana are highly susceptible to a variety of disarmed A. tumefaciens
      strains, and the transformation system is amenable to a number of selection
      agents. This protocol has proved to be easily transferable to a point at which a
      single investigator with minimal training can generate thousand of events per
      year. Moreover, seed size and quantity per event permit monitoring of segregation
      in Petri plates, and sufficient biomass can be accrued from an individual plant,
      which can be either clonally propagated or allowed to self-pollinate or easily
      outcrossed.

PMID- 16988342
TI  - Generation of composite plants using Agrobacterium rhizogenes.
AB  - Limitations in transformation capability can be a significant barrier in making
      advances in our understanding of gene function through the use of transgenics. To
      this end we have developed both tissue culture and non-tissue culture-based
      methodologies for the production of transgenic roots on wild-type shoots
      (composite plants). Composite plants are generated by inoculating wild-type
      shoots with Agrobacterium rhizogenes, which subsequently induces the formation of
      transgenic roots. The composite plant system allows for "in root" testing of
      transgenes in the context of a complete plant and can be analyzed in a variety of
      gene function analyses and plant-microbe interaction studies. In this chapter we
      provide a tissue culture-based composite plant generation system for Arabidopsis
      and a non-tissue culture based-method for producing composite plants on a variety
      of dicotyledonous plant species. Composite plants generated using these methods
      can be treated like "normal plants," planted in soil and grown in greenhouses or
      in growth chambers. These methods have been shown to work efficiently for many
      different species of plants including several that are recalcitrant to
      transformation.

PMID- 16988343
TI  - Barley (Hordeum vulgare L.).
AB  - Crop improvement is limited by the availability of valuable traits in sexually
      compatible species. Access to new characters using genetic engineering would be
      of great value. Barley has been transformed using microprojectile bombardment and
      by direct gene transfer to protoplasts, but neither method has been able to
      produce fertile transformants in large numbers with simple transgene integration
      characteristics. Agrobacterium-mediated transformation was first achieved in
      1997, and it has become the method of choice. Using immature embryos of the
      barley variety Golden Promise as the target organ, the binary vector pWBVec8
      containing the intron-interrupted hygromycin resistance gene hph as the
      selectable marker, and selection of transformed cells on hygromycin, the
      Agrobacterium method is efficient, and the transgene insertion characteristics
      are superior to other methods. However, the procedure is strongly genotype
      dependent. In this report, we describe a transformation protocol giving details
      of plant culture, embryo isolation and preparation, vector details, Agrobacterium
      culture, infection methods, subsequent procedures for callus generation and
      plantlet production, and analysis of transgenic plants.

PMID- 16988344
TI  - Maize (Zea mays L.).
AB  - Agrobacterium tumefaciens-mediated transformation is an effective method for
      introducing genes into maize. In this chapter, we describe a detailed protocol
      for genetic transformation of the maize genotype Hi II. Our starting plant
      material is immature embryos cocultivated with an Agrobacterium strain carrying a
      standard binary vector. In addition to step-by-step laboratory transformation
      procedures, we include extensive details in growing donor plants and caring for
      transgenic plants in the greenhouse.

PMID- 16988345
TI  - Indica rice (Oryza sativa, BR29 and IR64).
AB  - Rice is the world's most important food crop. Indica-type rice provides the
      staple food for more than half of the world population. To satisfy the growing
      demand of the ever-increasing population, more sustained production of indica
      type rice is needed. In addition, because of the high per capita consumption of
      indica rice, improvement of any traits including its nutritive value may have a
      significant positive health outcome for the rice-consuming population. Rice yield
      productivity is greatly affected by different biotic stresses, like diseases and
      insect pests, and abiotic stresses like drought, cold, and salinity. Attempts to
      improve resistance in rice to these stresses by conventional breeding through
      introgression of traits have limited success owing to a lack of resistance
      germplasm in the wild relatives. Gene transfer technology with genes from other
      sources can be used to make rice plants resistant or tolerant to insect pests,
      diseases, and different environmental stresses. For improving the nutritional
      value of the edible endosperm part of the rice, genes for increasing iron, beta
      carotene, or better quality protein can be introduced in rice plants by genetic
      engineering. Different crops have been transformed using various gene transfer
      methods, such as protoplast transformation, biolistic, and Agrobacterium-mediated
      transformation. This chapter describes the Agrobacterium-mediated transformation
      protocol for indica-type rice. The selectable marker genes used are hygromycin
      phosphotransferase (hpt), neomycin phosphotransferase (nptII), or phosphomannose
      isomerase (pmi), and, accordingly, the selection agents are hygromycin, kanamycin
      (G418), or mannose, respectively.

PMID- 16988346
TI  - Japonica rice varieties (Oryza sativa, Nipponbare, and others).
AB  - Agrobacterium-mediated transformation of rice is now used in many laboratories
      worldwide. Several protocols have been developed and fine-tuned for particular
      genotypes, including commercial genotypes, making use of either mature seeds or
      immature embryos as target tissue for Agrobacterium infection. In this chapter,
      we describe a rapid and user-friendly protocol based on mature seeds that can
      deliver transgenic rice plant-lets within 2 mo. The protocol described is based
      on the use of the nptII selectable marker gene. The tissue culture steps rely on
      Agrobacterium infection of whole young seedlings and on the induction and
      proliferation of highly embryogenic tissue. Importantly, we have validated the
      robustness and reliability of this protocol at a high-throughput scale for
      several japonica genotypes. We also provide some key features that can be further
      explored for the fine-tuning of this transformation protocol for any other
      genotype with a particular emphasis on the importance of tissue handling and
      subculture sequence.

PMID- 16988347
TI  - Rye (Secale cereale L.).
AB  - Rye (Secale cereale L.) is one of the most recalcitrant plant species for tissue
      culture and genetic transformation. Embryogenic rye callus loses its ability to
      regenerate plants quickly in response to high density of Agrobacterium and other
      stressors. The cocultivation of Agrobacterium and rye immature embryos in liquid
      medium facilitated washing of the cultures to avoid Agrobacterium overgrowth and
      allowed a high throughput. More than 40 independent transgenic plants were
      regenerated with one to four Southern-positive, independent events from 100
      inoculated immature embryos. Agrobacterium strain AGL0 supported stable
      integration of a constitutive nptII selectable marker expression cassette into
      the genome of rye inbred line L22, as indicated by regeneration of plantlets on
      paromomycin-containing culture medium, Southern blot, Western blot, and the
      analysis of T-DNA::plant DNA boundary sequences. Transgenic plants were
      phenotypically normal and fully fertile, which might be a consequence of the
      short time in tissue culture.

PMID- 16988348
TI  - Sorghum (Sorghum bicolor L.).
AB  - This chapter describes a stepwise protocol for Agrobacterium-mediated sorghum
      genetic transformation. Immature embryos from sorghum plants were used as the
      target explants. The Agrobacterium strain LBA4404, carrying a "super-binary"
      vector, was used in this protocol. Agrobacterium co-transformation vectors, one T
      DNA containing the selectable marker gene and another T-DNA containing the trait
      gene(s), were also introduced in sorghum transformation for eliminating the
      selectable marker gene in the resulting transgenic plants. This chapter provides
      recommendations for analysis of the transgenic plants to confirm T-DNA
      integration into the sorghum genome and segregation of the selectable marker gene
      from the trait gene(s).

PMID- 16988349
TI  - Wheat (Triticum aestivum L.).
AB  - This chapter describes a procedure for Agrobacterium-mediated wheat
      transformation. Freshly isolated immature embryos, precultured immature embryos,
      or embryogenic calli are inoculated with a disarmed A. tumefaciens strain C58
      (ABI) harboring the binary vector pMON18365 containing the beta-glucuronidase
      (GUS) gene with an intron, and a selectable marker, neomycinphosphotranferase
      (NPT) II gene. The inoculated explants are selected on callus induction medium
      with the selective agent G418 for approximately 2 wk. The resistant callus pieces
      that develop are then transferred onto medium with the selective agent and
      reduced plant growth regulators for plant regeneration and further selection. It
      takes approximately 2.5 to 3 mo from inoculation to the establishment of R0
      plants in soil. All the transformants should be morphologically normal and set
      seeds. Approximately 35% of the transgenic plants have a single copy of the
      transgene based on data obtained from previous experiments.

PMID- 16988350
TI  - Canola (Brassica napus L.).
AB  - High-frequency Agrobacterium tumefaciens-mediated transformation can be obtained
      in canola by optimizing the preconditioning time of the explant and cocultivation
      time with A. tumefaciens. A preconditioning time of 72 h and cocultivation of 48
      h synergistically increase the transformation efficiency to 25%. In addition, the
      recovery of transgenic plants can be facilitated by overcoming hyperhydration,
      which increases the rooting frequency to 100%.

PMID- 16988351
TI  - Cotton (Gossypium hirsutum L.).
AB  - Considering the economic importance of cotton in many developing and developed
      countries, there is an urgent need to accelerate the application of
      biotechnological tools to address the problems associated with the production of
      this crop and to improve the quality of fiber and seed. This requires a simple
      yet robust gene delivery/transformant recovery system. A protocol for the
      production of transgenic cotton plants was refined in our laboratory. It involves
      Agrobacterium-mediated transformation of cotton cells, selection of stable
      transgenic callus lines, and recovery of plants via somatic embryogenesis. A
      detailed description of the protocol is provided in this chapter.

PMID- 16988352
TI  - Indian mustard [Brassica juncea (L.) Czern.].
AB  - All economically important Brassica species have been successfully transformed
      using Agrobacterium tumefaciens. Although different tissues have been used as
      explants, hypocotyls remain the most desirable explants for Brassica tissue
      culture owing to their amenability to regeneration. Young explants excised from 3
      to 4-d-old seedlings have exhibited optimal regeneration potential; the addition
      of adjuvants such as silver nitrate to the selection medium is necessary to
      achieve high efficiency of transformation. This chapter describes an
      Agrobacterium-mediated transformation protocol for Indian mustard based on
      inoculation of hypocotyls. The selectable marker gene used encodes for neomycin
      phosphotransferase II (nptII), and the selection agent is kanamycin.

PMID- 16988353
TI  - Sunflower (Helianthus annuus L.).
AB  - Sunflower (Helianthus annuus L.) is considered one of the recalcitrant species in
      terms of transformation and regeneration. A routine transformation system of this
      crop requires competent cell cultures for efficient plant regeneration as well as
      an effective method for gene delivery. A transformation system was developed by
      an Agrobacterium tumefaciens-mediated method using split mature embryonic axis
      explants from the Ha89 genotype. Mean transformation efficiency obtained
      (measured as PCR+ plants/treated explants) varied from 1 to 5.2% depending on the
      use of the EHA105 or the C58 strain containing a plasmid with a gene of agronomic
      interest. The system developed has applicability to several Agrobacterium strains
      and plasmids with both reporter genes or genes of agronomic interest. Plants
      obtained with this protocol were confirmed by PCR and Southern blot. Stable
      inheritance of transgenes was successfully followed until generation T4 in
      several independent lines.

PMID- 16988354
TI  - Alfalfa (Medicago sativa L.).
AB  - A protocol for rapid, highly efficient transformation of alfalfa is described.
      Leaf explants from growth chamber-grown plants of a highly regenerable genotype
      are surface-sterilized, the margins are removed, and explants are inoculated with
      Agrobacterium tumefaciens strain LBA4404 carrying the T-DNA vector of interest.
      The explants and bacteria are cocultured for 7 to 8 d. Bacteria are removed by
      rinsing explants in sterile distilled water and by culture on regeneration medium
      containing the antibiotics carbenicillin or ticarcillin. Transformed callus is
      selected using kanamycin. Somatic embryos are induced by culture of callus on
      medium lacking plant growth regulators. As mature cotyledonary stage embryos
      arise, they are transferred to a fresh medium for shoot development and finally
      to a medium lacking kanamycin for continued shoot and root development.
      Transgenic plants can be produced in 9 wk with this protocol. Typically 60 to 80%
      of inoculated explants produce transgenic plants, and escapes are rare.

PMID- 16988355
TI  - Chickpea (Cicer arietinum L.).
AB  - Chickpea is one of the most important leguminous, cool-season, food crops,
      cultivated prevalently in the Asian Pacific region. In spite of its nutritional
      importance, its area of cultivation has been low, with virtually no increase.
      Conventional breeding has resulted in several important improvements in this
      crop, and recent advances in biotechnology such as plant tissue culture and
      genetic transformation can significantly contribute to better sustainability of
      this important food crop. Here, we describe an efficient Agrobacterium-mediated
      transformation protocol for chickpea using axillary meristem explants, which
      results in a high frequency of genetic transformation (70%) and recovery of
      valuable transgenic plants. The protocol is significant owing to its high
      reproducibility and recovery of the transgenics in a relatively short period (90
      100 days).

PMID- 16988356
TI  - Clovers (Trifolium spp.).
AB  - Legumes constitute one of the most important global groups of agricultural
      species, providing a major source of protein and oil for humans and animals as
      well as fixing nitrogen and improving the fertility of soils. Gene technology can
      assist plant improvement efforts in clovers (Trifolium spp.), aiming to improve
      forage quality, yield, and adaptation to biotic and abiotic stresses. An
      efficient and reproducible protocol for Agrobacterium-mediated transformation of
      a range of Trifolium species, using cotyledonary explants and different
      selectable marker genes, is described. The protocol is robust and allows for
      genotype-independent transformation of clovers. Stable meiotic transmission of
      transgenes has been demonstrated for selected transgenic clovers carrying single
      T-DNA inserts recovered from Agrobacterium-mediated transformation. This
      methodology can also be successfully used for 'isogenic transformation' in
      clovers: the generation of otherwise identical plants with and without the
      transgene from the two cotyledons of a single seed.

PMID- 16988357
TI  - Peas (Pisum sativum L.).
AB  - In this chapter we describe a robust method for transformation of peas that has
      been successfully used in our laboratory since 1992. Using immature pea seed
      collected from field- or greenhouse-grown plants, we have produced transgenic
      lines for over 30 genotypes including named pea cultivars and advanced breeding
      lines. This method uses immature cotyledons as the explant, and the
      transformation efficiency is in the range 0.2 to 13.5% of cotyledons producing at
      least one independently transformed line. Agrobacterium tumefaciens strains AGL1
      and KYRT1 are the most successful in our procedure, and kanamycin,
      phosphinothricin, and hygromycin are reliable selectable markers. Potentially
      useful genes have been introduced for pest and disease resistance, altering
      quality traits, and investigating metabolic pathways and are being studied in
      transgenic pea lines.

PMID- 16988358
TI  - Peanut (Arachis hypogaea L.).
AB  - Arachis hypogea (peanut, groundnut), an annual oil seed belonging to the
      Leguminosae family and the Papillionacea subfamily, is a legume native to South
      America but now grown in diverse environments in six continents between latitudes
      40 degrees N and 40 degrees S. Arachis hypogea can grow in a wide range of
      climatic conditions. The low yields of this crop are mainly attributed to
      unreliable rainfall patterns with frequent droughts, lack of high-yielding
      adapted cultivars, damage by diseases and pests, poor agronomic practices, and
      limited use of inputs. Genetic engineering approaches have been shown to be
      comparatively fast, leading to better isolation and cloning of desired traits for
      combating the various biotic and abiotic stresses. This chapter describes an
      Agrobacterium-mediated transformation protocol in peanut using the cotyledon
      system. The system described here is potentially applicable to a vast range of
      genotypes with a high transformation frequency of >70% based on the preliminary
      molecular data, indicating the production of a large number of independently
      transformed transgenic plants. The method reported here provides opportunities
      for crop improvement of this important legume crop via genetic transformation.

PMID- 16988359
TI  - Pigeonpea (Cajanus cajan L. Millsp.).
AB  - Pigeonpea [Cajanus cajan (L.) Millsp.], also known as redgram, is one of the
      major grain legume (pulses) crops grown in the semiarid tropics (SAT) extending
      between 30 degrees N and 30 degrees S; it is the second most important food
      legume of India. It is cultivated in about 50 countries of Asia, Africa, and the
      Americas for a variety of uses (food, fodder, fuel wood, rearing lac insects,
      hedges, wind breaks, soil conservation, green manure, roofing, and so on). The
      constraints of enhancing its productivity include the damage caused by various
      fungi, bacteria, viruses, and insect pests. Conventional plant breeding methods
      have not been successful for the improvement of pigeonpea because of genetic
      variation and incompatibility among the wild varieties. Genetic engineering
      technology can therefore be used as an additional tool for the introduction of
      agronomically useful traits into established varieties. The development of plant
      transformation techniques has been a major breakthrough in overcoming constraints
      to achieve precision in genetic manipulation. The development of efficient plant
      regeneration protocols is a prerequisite for recombinant technology to carry out
      genetic transformation. This chapter describes an Agrobacterium-mediated
      transformation protocol for pigeonpea, a simple, efficient, and reproducible
      method that is applicable across diverse genotypes of pigeonpea.

PMID- 16988360
TI  - Red clover (Trifolium pratense).
AB  - Genetic modification of plants by the insertion of transgenes can be a powerful
      experimental approach to answer basic questions about gene product function. This
      technology can also be used to make improved crop varieties for use in the field.
      To apply this powerful tool to red clover, an important forage legume, a
      population of red clover with a high potential for regeneration in tissue culture
      has been developed. Here we provide a detailed procedure for Agrobacterium
      mediated transformation of genotypes derived from this regenerable population. We
      have successfully used this methodology to express a beta-glucuronidase (GUS)
      reporter gene and to silence an endogenous polyphenol oxidase gene in red clover.

PMID- 16988361
TI  - Soybean (Glycine max) transformation using mature cotyledonary node explants.
AB  - Agrobacterium tumefaciens-mediated transformation of soybeans has been steadily
      improved since its development in 1988. Soybean transformation is now possible in
      a range of genotypes from different maturity groups using different explants as
      sources of regenerable cells, various selectable marker genes and selective
      agents, and different A. tumefaciens strains. The cotyledonary-node method has
      been extensively investigated and across a number of laboratories yields on
      average greater than 1% transformation efficiency (one Southern-positive,
      independent event per 100 cotyledonary-node explants). Continued improvements in
      the cotyledonary-node method concomitant with further increases in transformation
      efficiency will enhance broader adoption of this already productive
      transformation method for use in crop improvement and functional genomics
      research efforts.

PMID- 16988362
TI  - Soybean (Glycine max) transformation using immature cotyledon explants.
AB  - Agrobacterium tumefaciens-mediated transformation of soybeans can be accomplished
      using immature zygotic cotyledons as target tissues providing an alternate
      explant to embryogenic tissue cultures, proliferating meristems, and cotyledonary
      nodes. The immature cotyledon method includes direct induction of transgenic
      somatic embryos from the explant plated on selective media after cocultivation,
      followed by maturation and regeneration of individual somatic embryos into whole
      plants. Although this method has been improved to be simple, rapid, reproducible,
      and applicable to a range of cultivars in different maturity groups, the
      transformation efficiency (Southern-positive, independent plants produced per 100
      immature cotyledon explants) is 1.7% and needs to be further increased to make
      this a robust soybean transformation system. Further refinements of cocultivation
      conditions, tissue culture, and selection of regenerated transgenic plants will
      probably result in increases in transformation efficiency.

PMID- 16988363
TI  - Tepary bean (Phaseolus acutifolius).
AB  - Phaseolus beans are among the major legumes for food consumption, especially in
      Latin America, Africa, and Asia. Tepary bean (Phaseolus acutifolius L. Gray) is
      one of the five cultivated species of the genus Phaseolus. This chapter describes
      an Agrobacterium-mediated transformation protocol for P. acutifolius based on
      cocultivation of callus, derived from cotyledonary nodes, with Agrobacterium. The
      selectable marker gene used is neomycin phosphotransferase II (nptII), and the
      selection agent is geneticin. Selection of transgenic callus material is achieved
      through four to five passages on geneticin-containing medium, after which shoots
      are induced on medium without selection agent. The protocol as described here has
      been applied to transform a cultivated variety of P. acutifolius, TB1, and also
      with some modifications to a wild genotype, NI576 and another cultivated variety,
      PI440795.

PMID- 16988364
TI  - Brassica oleracea.
AB  - A better understanding of the genetic basis underlying the genotype dependence of
      Brassica oleracea transformation is enabling researchers to distinguish between
      recalcitrant and successful candidate genotypes for routine transformation. In
      this chapter we outline an A. tumefaciens-mediated transformation method for B.
      oleracea using 4-d-old cotyledonary explants and a model B. oleracea doubled
      haploid genotype, AG DH1012. After only 3 wk on kanamycin selection, the first
      transgenic shoots can be isolated. Transformation efficiencies in the region of
      10 to 25% (based on 50-125 PCR-positive independent shoots from 500 infected
      explants) are typically achieved. For researchers wishing to use their own plant
      genotype, we highlight the tissue culture phenotypes that are conducive to
      efficient transformation.

PMID- 16988365
TI  - Cucumber (Cucumis sativus L.).
AB  - We describe two novel Agrobacterium tumefaciens-based methods of cucumber
      transformation. The first involves direct regeneration from leaf microexplants
      selected on kanamycin-containing medium. The second involves regeneration from a
      long-term established embryogenic suspension culture emitting green
      autofluorescence (GAF) and selection on medium containing hygromycin. In the
      latter method, GAF was used as a reporter, thereby allowing a simple and reliable
      identification of transgenic cells with a high regeneration capacity. (No false
      positives were observed.) The transformation efficiency in the leaf microexplants
      fluctuated from 0.8 to 6.5% of the primary explants, whereas in the embryogenic
      suspension-cultured cells it varied from 6.4 to 17.9% of the aggregates. In the
      GAF method, the step involving the elimination of the Agrobacterium cells by
      antibiotics could be omitted; however, this reduced the transformation efficiency
      to about 3%. The time required from inoculation to regenerated plant in the
      greenhouse was the same for both methods, but the GAF method required more
      preinoculation time than the leaf microexplant method.

PMID- 16988366
TI  - Eggplant (Solanum melongena L.).
AB  - Eggplant is an economically important vegetable crop in Asia and Africa, and
      although it is grown in Europe and the United States, it does not account for a
      significant percentage of agricultural production. It is susceptible to a number
      of pathogens and insects, with bacterial and fungal wilts being the most
      devastating. Attempts to improve resistance through introgression of traits from
      wild relatives have had limited success owing to sexual incompatibilities.
      Therefore, a crop improvement approach that combines both conventional breeding
      and biotechnological techniques would be beneficial. This chapter describes an
      Agrobacterium-mediated transformation protocol for eggplant based on inoculation
      of seedling explants (cotyledons and hypocotyls) and leaves. We have used this
      protocol to recover transformants from two different types of eggplant, a Solanum
      melongena L. breeding line, and S. melongena L. var. Black Eggplant. The
      selectable marker gene used was neomycin phosphotransferase II (nptII) and the
      selection agent was kanamycin. In vitro grown transformants acclimated readily to
      greenhouse conditions.

PMID- 16988367
TI  - Lettuce (Lactuca sativa L.).
AB  - Lettuce is a globally important leafy vegetable with the United States being the
      largest world producers. The crop is susceptible to a number of viruses that are
      aphid transmitted and also highly vulnerable to post harvest diseases. Although
      wild species of lettuce are an important source of disease resistance genes,
      their introgression into commercial lettuce has been limited owing to sexual
      incompatibilities. Hence, the development of a gene transfer system for lettuce
      would be extremely valuable both in improving the genetic diversity of the crop
      and also for the transfer of useful agronomic traits. This chapter describes an
      Agrobacterium-mediated gene delivery system that is highly adaptable for the
      production of transgenic plants using a wide range of lettuce germplasms. The
      system described, commonly referred to as the genotype-independent transformation
      system, has been used for the transfer of several agriculturally useful traits
      into commercial varieties of lettuce. In this case, A. tumefaciens strain LBA4404
      carrying a binary vector with supervirulent pToK47 was used for infecting excised
      cotyledonary explants. The plant selectable marker gene neomycin
      phosphotransferase II (nptII) was used, and transformed plants were selected
      using kanamycin in the culture medium. The beta-glucuronidase gene with intron
      (gus-intron) was also used in the gene transfer study to confirm the
      transgenicity of regenerated plants further.

PMID- 16988368
TI  - Tomato (Lycopersicum esculentum).
AB  - Tomato (Lycopersicum esculentum) is an important fruit crop in the Americas,
      southern Europe, the Middle East, and India, with increasing production in China,
      Japan, and Southeast Asia. It is amenable to producing pharmaceuticals,
      particularly for oral delivery; for many of the same reasons, it is a popular
      vegetable. Its fruit does not contain toxic substances and is palatable uncooked;
      it is easily processed; the plants are able to be propagated by seed or clonally
      by tip or shoot cuttings; the plants have a high yield of fruit; there is
      reasonable biomass and protein content; and they are easily grown under
      containment. This chapter describes Agrobacterium-mediated transformation of the
      tomato nucleus using cotyledons as explants. We have used this protocol to
      generate transgenic lines from several tomato cultivars expressing various genes
      of interest and selectable markers. We also provide protocols for molecular
      characterization of transgenic lines and batch processing tomato fruit.

PMID- 16988369
TI  - Origin and progress of nuclear transfer in nonmammalian animals.
AB  - This chapter traces the origin and progress of nuclear transfer that later became
      the paradigm for cloning animals. Classic studies in cytology, embryology, or
      genetics spanning more than five centuries that led to nuclear transfers in
      unicellular animals and to those in oocytes of insects, fish and amphibians are
      reviewed. The impetus for the development of successful nuclear transfers in
      amphibian oocytes in 1952 was to determine whether or not differentiated somatic
      cell nuclei are developmentally equivalent to zygote nuclei. Experiments in
      amphibians demonstrated several important results: (1) specialized somatic cell
      nuclei are extensively multipotent; (2) fertile adult amphibians can be cloned
      from embryonic and larval nuclei; (3) serial cloning expands the number of
      clones; (4) transplanting nuclei into oocyte cytoplasm induces reprogramming of
      their gene function; and (5) amphibian cloning became the model for cloning
      mammals. Subsequent studies in mice, a more technically favorable species,
      revealed that specialized cell nuclei are equivalent to zygote nuclei.

PMID- 16988370
TI  - In vitro maturation and embryo production in cattle.
AB  - When immature bovine oocytes are released from their follicles and are cultured
      in standard maturation medium, they resume the first meiotic division. The
      alteration of basic maturation conditions can affect oocyte competence
      significantly, as reflected by the morula and blastocyst yield after in vitro
      fertilization. The conditions used from the beginning of maturation up to the
      blastocyst stage have been shown to influence not only the developmental
      competence but also, potentially, the normal epigenetic make-up of the embryo.
      The methods described in this chapter outline the different steps of in vitro
      production of bovine embryos up to the blastocyst stage in semidefined
      conditions: (1) oocyte maturation, (2) in vitro fertilization, and (3) in vitro
      development. The first section explains procedures of ovary collection and oocyte
      aspiration and selection for in vitro maturation. The second section involves
      methods for the preparation of semen and oocytes for fertilization. The last
      section explains the best conditions to obtain blastocysts after 8 d of in vitro
      culture.

PMID- 16988371
TI  - Activation of oocytes after nuclear transfer.
AB  - After nuclear transfer, the recipient oocyte must be stimulated to initiate
      development. This stimulation is achieved by inducing changes in the oocyte
      cytoplasm that normally are triggered by the sperm during fertilization. In most
      cases, such changes include a transient increase in the intracellular-free
      calcium concentration induced by an electrical pulse or alternatively, by
      chemical agents. Many times, particularly in aged oocytes, this calcium signal is
      sufficient to stimulate the oocyte developmental program. Other activation
      protocols were designed to target pathways downstream of the initial calcium
      signal to affect the activity of regulatory proteins that play central roles in
      maintaining developmental arrest. This is achieved by the application of protein
      kinase or protein synthesis inhibitors; combined with a calcium stimulus such
      inhibitors are widely used for oocyte activation after nuclear transfer and are
      able to support embryonic development to term.

PMID- 16988372
TI  - Culture medium preferences of pre-implantation cloned mouse embryos.
AB  - Somatic cloning technology involves the transfer of a somatic cell nucleus into
      an enucleated oocyte, followed by activation and in vitro culture. Efficiency in
      terms of live offspring generally remains very low. Little attention has been
      devoted so far to the impact of culture environment on cloned embryo development.
      Failure of genomic reprogramming of the donor nucleus in nuclear transfer (NT)
      experiments could lead to an altered phenotype in these cloned embryos that could
      be manifested by different medium preferences of the NT embryos. We describe here
      the application of sequential culture media to support preimplantation
      development of mouse embryos reconstructed using conventional NT techniques.
      Embryo-quality analysis was performed on NT blastocysts obtained. Additionally,
      NT embryos that arrested during development also were analyzed.

PMID- 16988373
TI  - Maintenance of pregnancy in pigs with limited viable embryos.
AB  - Interest is increasing in assisted reproductive technologies in the pig involving
      embryo cryopreservation, cloning, and genetic modification. Although inherently
      inefficient and variable in their outcome, the successful application of these
      techniques in this species is confounded by unique mechanisms for pregnancy
      recognition and maintenance that require a minimum number of viable embryos
      during a critical window of time early in gestation. These mechanisms require
      both local and systemic interactions between conceptuses and the maternal
      reproductive axis. Here, we describe a method wherein cotransfer of
      parthenogenetic embryos with the capacity for limited development can be used to
      sustain the pregnancy of fewer than four viable conceptuses to term.

PMID- 16988374
TI  - Health and neonatal care of bovine clones.
AB  - The management of clone-bearing recipients and neonatal clones is a critical
      component of successful cloning of mammals by nuclear transfer. The methodology
      discussed in this chapter is based largely on a double corticosteroid regime to
      induce parturition and fetal organ maturation in bovine clones. Lung maturation,
      particularly, is a major factor in clone calf viability. The animal health care
      involved in maximizing clone survival begins at embryo transfer and continues for
      the life of that animal.

PMID- 16988375
TI  - Optimization of procedures for cloning by somatic cell nuclear transfer in mice.
AB  - Cloning by somatic cell nuclear transfer is a complex procedure that is dependent
      on correct interactions between oocyte and donor cell genome. These interactions
      require minimal insult to either the oocyte or the transplanted nucleus.
      Available data also indicate that reprogramming the donor cell genome may be
      slow, so that the cloned embryo expresses genes typical of the donor cell, and
      thus has different characteristics from normal embryos. Procedures that minimize
      damage to the donor genome and that address the unique characteristics of the
      cloned construct should enhance the efficacy of the method.

PMID- 16988376
TI  - Production of cloned calves using roscovitine-treated adult somatic cells as
      donors.
AB  - The stage of the donor cell cycle is a major factor in the success of cloning.
      Quiescent cells arrested in the G0/G1 phases of the cell cycle by either serum
      starvation or growth arrest when cultured cells reach confluence have been used
      as donors to produce cloned animals. Recently, we have developed a novel and
      effective method using roscovitine to synchronize adult bovine granulosa cells in
      the G0/G1 cell cycle stage. The resulting fetal and calf survival after transfer
      of cloned embryos was enhanced in the roscovitine-treated group compared with
      serum-starved controls. The methods described in this chapter outline (1) the
      preparation of donor cells, (2) the preparation of recipient oocytes, and (3) the
      production of cloned embryos. The first section involves methods for the
      preparation of donor cell stocks from isolated granulosa cells and the
      roscovitine treatment of the cells before nuclear transfer. The second section
      explains procedures of in vitro maturation of recipient oocytes. The last section
      involves methods for the production of cell-oocyte complexes, the fusion of the
      complexes, and the activation, in vitro culture, and transfer into recipient
      females of cloned embryos.

PMID- 16988377
TI  - A double nuclear transfer technique for cloning pigs.
AB  - The first round of double nuclear transfer (NT) procedure includes the following
      steps: transfer of somatic cell nuclei into enucleated recipient oocytes, fusion,
      activation, and culture of reconstructed oocytes. The next day, a second round of
      NT is performed by removing karyoplasts from 1-d-old NT embryos and transferring
      them into in vivo-derived zygotes from which the two pronuclei have been removed.
      Couplets are then fused using an electrical pulse and transferred into
      synchronized recipient gilts. This system, which uses fertilized oocytes as
      cytoplast recipients, bypasses the inefficiencies of artificial activation
      procedures, and may promote more successful development.

PMID- 16988378
TI  - Nuclear transfer in nonhuman primates.
AB  - The nonhuman primate is a highly relevant model for the study of human diseases,
      and currently there is a significant need for populations of animals with
      specific genotypes that can not be satisfied by the capture of animals from the
      wild or by conventional breeding. There is an even greater need for genetically
      identical animals in vaccine development or tissue transplantation research,
      where immune system function is under study. Efficient somatic cell nuclear
      transfer (SCNT) procedures could provide a source for genetically identical
      nonhuman primates for biomedical research. SCNT offers the possibility of cloning
      animals using cultured cells and potentially provides an alternative approach for
      the genetic modification of primates. The opportunity to introduce precise
      genetic modifications into cultured cells by gene targeting procedures, and then
      use these cells as nuclear donors in SCNT, has potential application in the
      production of loss-of-function monkey models of human diseases. We were initially
      successful in producing monkeys by NT using embryonic blastomeres as the source
      of donor nuclei and have repeated that success. However, when somatic cells are
      used as nuclear donor cells, the developmental potential of monkey SCNT embryos
      is limited, and somatic cell cloning has not yet been accomplished in primates.
      High rates of in vitro development to blastocysts, comparable with in vitro
      fertilization controls, and successful production of rhesus monkeys by NT from
      embryonic blastomeres suggests that basic cloning procedures, including
      enucleation, fusion, and activation, are consistent with the production of viable
      embryos. Although modifications or additional steps in SCNT are clearly
      warranted, the basic procedures will likely be similar to those extant for
      embryonic cell NT. In this chapter, we describe detailed protocols for rhesus
      macaque embryonic cell NT, including oocyte and embryo production,
      micromanipulation, and embryo transfer in nonhuman primates.

PMID- 16988379
TI  - Cloning of exotic/endangered species: desert bighorn sheep.
AB  - Cloning using somatic cell nuclear transfer (SCNT) may be a useful tool for
      conserving genetic diversity and for propagating exotic and/or endangered animal
      species. Somatic cells can be obtained easily, expanded in culture,
      cryopreserved, and thawed at a later date for use in NT. Significant challenges
      relevant to using SCNT for cloning wild and endangered animal species include the
      need for using interspecies NT and interspecies embryo transfer. Animal care and
      welfare issues raised that are unique to exotic and endangered species also are
      raised. In this chapter, the methods used in attempts to clone the wild animal
      species of Desert Bighorn Sheep are described.

PMID- 16988380
TI  - Handmade somatic cell cloning in cattle.
AB  - Apart from the biological and ethical problems, technical difficulties also
      hamper the improvement and widespread application of somatic cell nuclear
      transfer (NT). Recently introduced zona-free procedures may offer a solution for
      the latter problem. The most radical approach of these techniques is the so
      called handmade cloning (HMC). It does not require micromanipulators because the
      manipulations required for both enucleation and nucleus transfer are performed by
      hand. The HMC technique includes manual bisection of zona-free oocytes, selection
      of cytoplasts by staining, and the simultaneous fusion of the somatic cell with
      two cytoplasts to produce a cloned embryo. HMC is a rapid and efficient technique
      that suits large-scale NT programs. It requires less expertise and time than
      traditional NT methods and the cost of equipment is significantly less.
      Production efficiency is high and embryo quality, in terms of pregnancy rates and
      live births, is not compromised. Although HMC has been developed particularly for
      bovine NT, the technique is applicable to other species. The method may become a
      useful tool for both experimental and commercial somatic cell cloning because it
      allows for standardization of procedures and provides the possibility of
      automation.

PMID- 16988381
TI  - Genetic modification of sheep by nuclear transfer with gene-targeted somatic
      cells.
AB  - For many years the lack of germline competent embryonic stem cell lines in
      livestock meant that the targeted modification of endogenous genes was not
      possible in these species. The demonstration that livestock could be cloned by
      nuclear transfer from cultured somatic cells has now provided an alternative
      route to accomplish gene targeting. This chapter describes protocols for
      culturing primary sheep fibroblasts, introducing and selecting targeted
      modifications into them and then using these modified cells in nuclear transfer
      experiments.

PMID- 16988382
TI  - Transgenesis using nuclear transfer in goats.
AB  - Nuclear transfer (NT) using transgenic donor cells is an efficient means for
      generation of transgenic founder goats, especially in regard to the number of
      animals required to produce a transgenic founder expressing the protein of
      interest. Vectors can be designed for organ-specific expression and secretion of
      recombinant proteins within the target tissue. Furthermore, donor cells can be
      selected for gender, genetically modified to introduce the transgene of interest
      and screened for incorporation of the transgene into the genome before use in NT.
      This chapter describes methods for production of transgenic donor cells,
      subsequent NT embryo production, and transfer into recipients.

PMID- 16988383
TI  - Nuclear reprogramming: an overview.
AB  - Nuclear reprogramming is an intriguing phenomenon, in which specialized somatic
      cells reacquire pluripotency through the global resetting of epigenetic
      modifications without changes occurring to their nuclear DNA information. The
      nuclear reprogramming activity retained by unfertilized eggs and embryonic stem
      cells is readily observable through the techniques of nuclear transplantation and
      cell fusion, respectively. Furthermore, researches involving somatic stem cells
      have provided evidence that spontaneous cell fusion functions, at least in part,
      in maintaining the homeostasis of various tissues through the generation of
      replacement cells in vivo. Novel approaches by application of the nuclear
      reprogramming activity may open new avenues producing genetically matched
      personalized pluripotential stem cells derived from patient somatic cells.

PMID- 16988384
TI  - Expression of imprinted genes in cloned mice.
AB  - Genomic imprinting is a mammalian specific epigenetic modification of the genome.
      Assessment of the integrity of the imprinting memory in somatic cell cloned
      animals is important not only for understanding of the "reprogramming" process
      during cloning by nuclear transfer, but also for the applications of this
      technique for therapeutic cloning in the future. In this chapter, we summarize
      the analytical methods for assessment of monoallelic expression of imprinting
      genes and expression analysis. From a practical point of view, the authors
      suggest the use of intersubspecific F1 hybrids between the laboratory mouse (Mus
      musculus musculus) and the JF1 strain (Mus musculus molossinus). We also list the
      sequence for PCR primers to detect the polymorphism of imprinted genes between
      musculus and molossinus.

PMID- 16988385
TI  - Nuclear remodeling assay in Xenopus egg extract.
AB  - Xenopus egg extract is an ideal material to identify nuclear remodeling
      activities important for nuclear cloning. Since the protocol for egg extract
      preparation was established more than 20 yr ago, egg extract has been widely used
      as a source for the purification of factors associated with a number of
      physiological activities. The eggs are large, easily obtained in large
      quantities, and are abundant in a variety of bioactive proteins. Many aspects of
      somatic nuclear remodeling observed in nuclear cloning are recapitulated in
      somatic nuclei incubated in egg extract. Our in vitro nuclear remodeling assay
      has proven effective for the purification of two novel nuclear remodeling
      activities, ISWI, a key player in the dissociation of TATA binding protein from
      chromatin, and FRGY2a and FRGY2b, two proteins capable of nucleolar disassembly.
      Here we outline our protocol of egg extract preparation and in vitro nuclear
      remodeling assay, as well as the purification method for FRGY2a and FRGY2b. Our
      in vitro nuclear remodeling assay in combination with egg extract will serve as a
      powerful tool with which to biochemically uncover molecular events involved in
      nuclear cloning.

PMID- 16988386
TI  - In vitro reprogramming of nuclei and cells.
AB  - Directly turning a somatic cell type into another would be beneficial for
      producing replacement cells for therapeutic purposes. To this end, novel cell
      reprogramming strategies are being developed. We describe here methods for
      functionally reprogramming a somatic cell using an extract derived from another
      somatic cell type. The procedure involves reversible permeabilization of 293T
      fibroblasts, incubation of the permeabilized cells in a nuclear and cytoplasmic
      extract of T-cells, resealing of the "reprogrammed" cells, and culture for
      assessment of reprogramming. Reprogramming has been evidenced by nuclear uptake
      and assembly of transcription factors, induction of activity of a chromatin
      remodeling complex, changes in chromatin composition, activation of lymphoid cell
      specific genes, and expression of T-cell-specific surface molecules. The system
      is likely to constitute a powerful tool to examine the processes of nuclear
      reprogramming, at least as they occur in vitro.

PMID- 16988387
TI  - Techniques for nuclear transfer to mouse embryonic stem cells.
AB  - In this chapter, methods are described that permit the enucleation of mouse
      embryonic stem (ES) cells and the transfer of donor nuclei to these cells before
      or after enucleation has taken place. The small size and high nucleus-to
      cytoplasm volume ratio of ES cells poses a challenge to their enucleation. The
      first step describes the production of lines of larger, polyploid ES cells, which
      are more suited to enucleation than diploid ES cells. In a second step, a simple
      centrifugal enucleation technique is described that allows efficient bulk
      production of ES cell cytoplasts and karyoplasts. Finally, techniques for nuclear
      transfer to ES cells are described, involving either transfer of karyoplasts to
      cytoplasts or the formation of heterokaryons between donor and recipient cells
      followed by the selective elimination of the polyploid nucleus. These methods
      have potential applications in the generation of autologous, diploid pluripotent
      cells from donor somatic cells. Also, they provide a novel dynamic model for
      studying nucleocytoplasmic interactions in ES cells.

PMID- 16988388
TI  - Gene expression and methylation patterns in cloned embryos.
AB  - A considerable proportion of the offspring, in particular in ruminants and mouse,
      born from nuclear transfer (NT)-derived and in vitro-produced (IVP) embryos are
      affected by multiple abnormalities, of which a high birthweight and an extended
      gestation length are the predominant features; a phenomenon that has been termed
      "Large Offspring syndrome" (LOS). According to a current hypothesis, LOS is
      caused by persistent aberrations of expression patterns of developmentally
      important genes starting as early as at the preimplantation stages. The
      underlying mechanisms are widely unknown at present, but epigenetic modifications
      of embryonic and fetal gene expression patterns, primarily caused by alterations
      in DNA methylation are thought to be involved in this syndrome. Appropriate DNA
      methylation is essential for regular transcription during mammalian development
      and differentiation. Sensitive reverse transcription polymerase chain reaction
      assays allow the study of messenger RNA (mRNA) expression levels of specific
      genes in single embryos. The methylation status of a specific gene can be
      assessed by bisulfite sequencing. Studies to unravel mRNA expression patterns
      from IVP- and NT-derived embryos have revealed numerous aberrations ranging from
      suppression of expression to de novo overexpression or more frequently to a
      significant upregulation or downregulation of a specific gene. mRNA expression
      patterns from in vivo-derived embryos are essential as the "physiological
      standard" against which the findings for IVP and NT-derived embryos are to be
      compared. Unraveling the underlying molecular mechanisms will contribute to the
      production of viable embryos and aid to improve biotechnologies applied to early
      mammalian embryos.

PMID- 16988389
TI  - Are there any normal clones?
AB  - An exhaustive study of the fidelity of a clone to its parent is prohibitive
      because of cost and the necessary scope of experimental design. Therefore, these
      data must be gathered from existing observational evidence. This in itself cannot
      provide a definitive accounting of the abnormalities and variation found among
      clones or between clones and parents because there is no standardization in the
      data points collected between one study and another. This literature survey shows
      that clone developmental abnormalities, variation among clones, and variation
      between clone and parent are prevalent at most stages of development (cleavage,
      placental, fetal, neonatal, maturity), and that occasionally the observed
      variation greatly exceeds that which might be expected. Some variation can be
      explained by differences in protocols and procedures between studies. The choice
      of nuclear donor cell is particularly influential of variation observed between a
      clone and its parent. In general, however, it appears that there is an inherent
      stochastic response to nuclear transfer that results in clone infidelity and
      variation. The survey of characteristics of clone infidelity to parent and
      documentation of abnormalities provided here should not be viewed as exhaustive
      or limiting in the recording of such data from future studies. Because controlled
      hypothesis testing of clone fidelity or clone health may not be possible,
      meticulous documentation of such observational evidence is a valuable
      contribution to the field.

PMID- 16988390
TI  - Future and applications of cloning.
AB  - The birth of viable offspring from somatic cell nuclear transfer (SCNT) in
      mammals caused a major re-examination of the understanding of the commitment of
      cells to specific tissue lineages during differentiation. The questions of
      whether cells undergo dedifferentiation or transdifferentiation during the
      development of offspring and how these changes are controlled is a source of
      ongoing debate that is yet to be resolved. Irrespective of the outcome of this
      debate, it is clear that cloning using SCNT has a place and purpose in the future
      of research and animal breeding. The future uses of SCNT could include the
      production of transgenic mice, the production of transgenic livestock and
      assisting with the re-establishment of endangered species. Human medicine also
      would benefit from future use of SCNT because it would allow the production of
      patient-specific embryonic stem cells.

PMID- 16988391
TI  - Past, present, and future of high content screening and the field of cellomics.
AB  - High content screening (HCS) was created in 1996 to offer a new platform that
      could be used to permit relatively high-throughput screening of cells, in which
      each cell in an array would be analyzed at a sub-cellular resolution using
      multicolored, fluorescence-based reagents for both specificity and sensitivity.
      We developed HCS with the perspective of the history of the development of the
      automated DNA sequencers that revolutionized the field of genomics. Furthermore,
      HCS was based on a history of important developments in modern cytology. HCS
      integrates the instrumentation, application software, reagents, sample
      preparation, and informatics/bioinformatics required to rapidly flow from
      producing data, generating information, and ultimately creating new cellular
      knowledge. The HCS platform is beginning to have an important impact on early
      drug discovery, basic research in systems cell biology, and is expected to play a
      role in personalized medicine.

PMID- 16988392
TI  - A pharmaceutical company user's perspective on the potential of high content
      screening in drug discovery.
AB  - It is early to fully reflect on the state of the art in high content screening
      (HCS), because it is still a relatively new approach in drug discovery. Although
      the development of the first microscopes are a century old and the first confocal
      microscope is only 20 yr old, the fluorescent probes used within HCS along with
      the combination of robotic automation and integrated software technologies are
      quite new. HCS will require a few more years to fully demonstrate its potential
      power in drug discovery. Within the last year, however, one has seen this ever
      expanding field lure participants in from all areas of science, introducing newer
      versions of instruments and reagents such that the combined efforts result in
      platforms and tools that meet many organizational goals in multiple ways. The
      potential of HCS today lies in its versatility. HCS can be used for primary
      screening, basic research, target identification, biomarkers, cytotoxicity, and
      helping to predict clinical outcomes. HCS is being applied to stem cells, patient
      cells, primary hepatocytes, and immortalized cultured cells. We have noted for
      individual specialized assays, there are multiple solutions just as there are for
      those standardized universally accepted assays. Whether we have needed to query
      cellular processes under live conditions or wanted to follow kinetically the
      course of a compound's effects on particular cellular reactions, we have been
      hampered by only a few limitations. This chapter offers a glimpse inside the use
      of HCS in our drug discovery environment.

PMID- 16988393
TI  - Linking microscopy and high content screening in large-scale biomedical research.
AB  - Microscopy has been a cornerstone of discovery in the academic life sciences for
      more than 100 yr. This comes from a unique ability to provide extremely rich
      information of biological structure and dynamics. The advent of digital imaging
      and machine vision has brought within itself the ability to collect images more
      easily and critically, the ability to measure objects and intensities within
      images. Although many continue to use microscopy in a qualitative manner, the
      analytical capabilities afforded by machine vision are increasingly being applied
      to basic cell biology and biomedical research. Scalable quantitative imaging
      technology might enable scientists and engineers to determine structure,
      dynamics, and function of entire biological systems rather than individual
      molecules or pathways. This chapter will provide an overview of early efforts in
      the academic community to apply high content screening to the study of biological
      systems.

PMID- 16988394
TI  - Requirements, features, and performance of high content screening platforms.
AB  - High content screening (HCS) platforms integrate fluorescence microscopy with
      image analysis algorithms and informatics to automate cell analysis. The initial
      applications of HCS to secondary screening in drug discovery have spread
      throughout the discovery pipeline, and now into the expanding research field of
      systems cell biology, in which new manipulation tools enable the use of large
      scale screens to understand cellular pathways, and cell functions. In this
      chapter we discuss the requirements for HCS and the systems that have been
      designed to meet these application needs. The number of HCS systems available in
      the market place, and the range of features available, has grown considerably in
      the past 2 yr. Of the two general optical designs, the confocal systems have
      dominated the high-throughput HCS market, whereas the more cost effective wide
      field systems have dominated all other market segments, and have a much larger
      market share. The majority of available systems have been optimized for fixed
      cell applications; however, there is growing interest in live cell kinetic
      assays, and four systems have successfully penetrated this application area. The
      breadth of applications for these systems continues to expand, especially with
      the integration of new technologies. New applications, improved software, better
      data visualization tools, and new detection methods such as multispectral imaging
      and fluorescence lifetime are predicted to drive the development of future HCS
      platforms.

PMID- 16988395
TI  - Characteristics and value of directed algorithms in high content screening.
AB  - High content screening requires image processing algorithms that can accurately
      and robustly analyze large image numbers without requiring human intervention.
      Thus, a suite of algorithms that are directed by an understanding of the biology
      being studied was developed for the optimized automated acquisition and
      quantitation of cellular images. Two categories of directed algorithms were
      developed: Developer Tools for assay development and Specific Algorithms for
      turnkey screening of specific biological situations. The same basic sequence of
      analysis steps are used in these directed algorithms: 1. Primary object
      identification. 2. Measurement of primary object properties. 3. Identification
      and measurements of associated targets. 4. Analysis of raw measurements for
      specific biological problems. The detailed application of these steps is guided
      by the biology being studied and the expected phenotypic changes. Most cell
      biological problems to be analyzed using high content screening can be
      categorized by either the phenotype of the problem or labeling pattern, or by a
      standard biological response behavior of the cells. This enables application of
      directed algorithms optimized for these categories. Examples of the use of
      directed algorithms for specific categories are discussed, as well as the
      detailed analysis steps for a specific directed algorithm.

PMID- 16988396
TI  - Characteristics and value of machine learning for imaging in high content
      screening.
AB  - Requirements for a flexible image analysis package for high content screening
      (HCS) are discussed. An overview of tools and techniques for image analysis and
      machine learning is given. Machine learning for classification and segmentation,
      the two fundamental elements of image analysis, is discussed. Next generation
      image analysis packages for HCS are reviewed. Recommendations for the development
      of image analysis solutions for advanced assays are given.

PMID- 16988397
TI  - Tools for quantitative and validated measurements of cells.
AB  - In this chapter, we describe the preparation of thin films of collagen that can
      serve as reference materials for assuring reproducible and predictable cell
      responses. Subtle differences in the molecular-scale characteristics of
      extracellular matrix proteins, including the supramolecular structure of type 1
      collagen, can have tremendous influences on cell state and cell-signaling
      pathways; therefore the careful control and analysis of the culture surface is
      critical to assure a relevant and consistent response in cell-based assays. We
      also describe how cell-phenotypic parameters such as morphology, proliferation,
      and green fluorescent protein expression can be unambiguously quantified in
      adherent cells by automated fluorescence microscopy or high content screening.
      Careful consideration of protocols, and the use of fluorescent reference
      materials, are essential to assure day-to-day and instrument-to-instrument
      interoperability. The ability to collect quantitative data on large numbers of
      cells in homogeneous matrix environments allows assessment of the range of
      phenotypes that are reproducibly expressed in clonal cell populations. The
      inherent distribution of responses in a cell population will determine how many
      cells must be measured to reach an accurate determination of cellular response.

PMID- 16988398
TI  - Automated cell plating and sample treatments for fixed cells in high content
      assays.
AB  - Robust and reliable methods for the manipulation of neural cell lines, by
      passaging, plating, dye labeling, imaging, fixation, and immunocytochemistry, are
      required to enable consistent, reproducible screens to be performed. We describe
      herein procedures and processes we have established to maximize the level of
      consistency of cell plating, fixation, and dye or antibody labeling, to ensure
      that assays which we are running on a routine basis remain consistent across long
      periods of time. These procedures involve a variety of fully or semiautomated
      steps, using high-quality commercially available liquid handling and dispensing
      technology.

PMID- 16988399
TI  - Differentiating primary human cells in rapid-throughput discovery applications.
AB  - Primary cultures of human cells provide an increasingly important alternative to
      using virally transformed or otherwise immortalized cell lines or to using cloned
      cell lines derived from human or animal tumors. Advances in primary cell culture
      techniques, media formulations, and other reagents have enabled routine culture
      of primary cells derived from human tissues for biomedical research and drug
      discovery approaches such as high content screening. That primary cells retain
      the phenotypic characteristics of the original tissue is one main advantage over
      immortalized cell lines. However, securing reliable supplies of primary cells on
      a large scale has been problematic. Here, two primary differentiating cell types,
      preadipocytes and preosteoclasts, are described to illustrate the utility of
      commercially produced cell systems in discovery research and rapid-throughput
      applications.

PMID- 16988400
TI  - Use of the CellCard System for analyzing multiple cell types in parallel.
AB  - The CellCard system enables the analysis of multiple cell types within a single
      microtiter well. In doing so, the CellCard system not only determines the effect
      of an experimental condition on a cell type of interest, but also the relative
      selectivity of that response across nine other cell types. In addition, this
      approach of cellular multiplexing is a means of miniaturization without the
      necessity of microfluidic devices. The standard 96-well plate generates ten 96
      well plates of data (or, the equivalent of a 960-well plate). Taken together, the
      CellCard technology enables multiple cell types to be assayed within a single
      microtiter well allowing for the simultaneous determination of cellular activity
      and compound selectivity. This chapter will describe a method by which multiple
      cell types can be simultaneously assayed for biological parameters of interest.

PMID- 16988401
TI  - Reagents to measure and manipulate cell functions.
AB  - Reagents that are used as part of a discovery platform for the measurement and
      manipulation of cell functions are at the heart of single and multiplexed high
      content screening assays. Measurement reagents include physiological indicators,
      immunoreagents, fluorescent analogs of macromolecules, positional biosensors, and
      fluorescent protein biosensors. Recent developments in reagents that manipulate
      specific cell functions including small inhibitory RNAs, caged peptides,
      proteins, and RNAs, and gene switches complement measurement reagents, especially
      when both classes of reagents are used in the same living cells. The use
      measurement and manipulation reagents in multiplexed high content screening
      assays promises to enable a systems cell biology approach to drug discovery and
      biomedical research.

PMID- 16988402
TI  - Fluorescent proteins and engineered cell lines.
AB  - Green fluorescent protein and other fluorescent proteins provide powerful tools
      for high content analysis of cellular processes. Engineering fluorescent protein
      sensors for expression in cellular assays requires consideration of a wide range
      of design factors to produce fusion proteins capable of generating informative
      and biologically relevant data while meeting the rigorous demands of high content
      screening. The target protein, fluorescent protein, host cell line, construct
      components and orientation, expression level, and other factors all contribute to
      the performance of the sensor. This chapter reviews the process of selecting an
      optimum combination of these design elements for engineering cells for high
      content analysis.

PMID- 16988403
TI  - Optimizing the integration of immunoreagents and fluorescent probes for
      multiplexed high content screening assays.
AB  - Immunoreagents formed the basis of early fixed end point high content screening
      (HCS) assays and their use in HCS applications in drug discovery will continue to
      increase. One important application of immunoreagents is their incorporation into
      multiplexed HCS assays in which multiple physiological features are
      simultaneously measured and related in the same cells. However, creating
      multiplexed HCS assays that incorporate multiple immunoreagents presents issues
      such as reagent compatibility, spectral signal overlap, and reproducibility that
      must be addressed. Here, an example multiplexed fixed end point HCS assay is used
      to guide potential assay developers on how to optimize complex, yet cellular
      information rich, multiplexed HCS assays although avoiding some common pitfalls.

PMID- 16988404
TI  - The HaloTag: a novel technology for cell imaging and protein analysis.
AB  - The ability to specifically label proteins with a wide range of optical
      properties and functionalities can help reveal information about protein
      functions and dynamics in living cells. Here, we describe a technology for
      covalent tethering of organic probes directly to a specially designed reporting
      protein expressed in live cells. The reporting protein can be used in a manner
      similar to green fluorescent protein, except that the fluorophore might be
      interchanged among a variety of standard dyes. This allows living cells to be
      imaged at different wavelengths without requiring changes to the underlying
      genetic constructs, and the colors can be rapidly switched to allow temporal
      analysis of protein fate. The stability of the bond permits imaging of live cells
      during long time periods, imaging of fixed cells, and multiplexing with different
      cell/protein analysis techniques. The dyes can also be exchanged with other
      functional molecules, such as biotin to serve as an affinity handle, or even
      solid supports for direct covalent immobilization. The technology complements
      existing methods and provides new options for cell imaging and protein analysis.

PMID- 16988405
TI  - Protein labeling with FlAsH and ReAsH.
AB  - The ability to image biochemical and phenotypical changes in living cells has
      become crucial for the investigation and understanding of the molecular
      mechanisms that govern all physiological cellular functions in health and
      disease. Genetically encoded reporters derived from fluorescent proteins (FPs)
      have proved to be extremely useful for localization and interaction studies in
      living cells. However, the large size and spectral properties of FP impose
      certain limitations for their use. The recently developed Fluorescein Arsenical
      Hairpin (FlAsH/tetracysteine) binder technology emerged as a promising
      alternative to FP for protein labeling and cellular localization studies. The
      combination of a small genetically encoded peptide tag with a small molecule
      detection reagent makes this technology particularly suitable for the
      investigation of biochemical changes in living cells that are difficult to
      approach with fluorescent proteins as molecular tags. We describe the practical
      application of this technology to image protein dynamics in living cells.

PMID- 16988407
TI  - Physiological indicators of cell function.
AB  - Successful high content screening (HCS) assays place large demands on the cell
      based reagents used in their development and deployment. Fortunately, there is a
      wide range of fluorescent physiological indicators from which to choose that are
      continually increasing in size and variety. Ideal fluorescent reagents for cell
      based assays exhibit optimal selectivity, signal intensity, and cell solubility,
      yet will be easily incorporated into assays across multiple detection platforms.
      The repertoire of existing fluorogenic and color changing dyes that indicate
      physiological changes in cells for live cell kinetic and fixed end-point assays
      are surveyed as well as newly developed reagents for the next generation of HCS
      assays.

PMID- 16988406
TI  - Exploiting network biology to improve drug discovery.
AB  - Mammalian signal transduction occurs in the context of multiprotein complexes,
      yet currently available drug discovery strategies do not reflect this fact. We
      present a strategy for screening drugs and targets in living human cells by
      utilizing high content protein-fragment complementation assays. Synthetic
      fragments of a mutant fluorescent protein ("Venus" and/or enhanced yellow
      fluorescent protein) are used for protein-fragment complementation assay
      construction, allowing us to measure spatial and temporal changes in protein
      complexes in response to drugs that activate or inhibit particular pathways. Here
      we describe the utility of this novel strategy for high-throughput screening of
      known targets, and for screening previously undrugable targets and profiling drug
      leads for improved selectivity and safety.

PMID- 16988408
TI  - The use of siRNA to validate immunofluorescence studies.
AB  - Cellular immunofluorescence studies can be validated by using either specific
      small interfering RNA (siRNA) duplexes or expression plasmids that induce the
      expression of specific siRNAs. The usage of either siRNA tool reduces the
      expression of the specific protein being studied, thus reducing substantially or
      abolishing the immunofluorescence detected when using a fluorescent antibody that
      recognizes the protein.

PMID- 16988409
TI  - Caged substrates applied to high content screening: an introduction with an eye
      to the future.
AB  - The use of photoremovable protecting groups in biology affords the end user high
      temporal, spatial, and concentration control of reagents and substrates. High
      content screening and other large-scale biology applications would benefit
      greatly from these advantages. Herein, we report progress in this field by
      highlighting the recent development of controllable siRNA (csiRNA), which is a
      dormant siRNA that can be activated using 365 nm light. Two different
      experimental designs are described to highlight the temporal and concentration
      variables that can be controlled. First, the RNAi process is activated at two
      timepoints, 24- and 48-h post-transfection, to demonstrate that the action of
      csiRNA does not begin until activated. Second, increasing light dosage exposure
      to cells transfected with csiRNA that controls the concentration of active siRNA
      molecules. All experiments are conducted in a 96-well format with light delivered
      through the UCOM device.

PMID- 16988410
TI  - Overview of informatics for high content screening.
AB  - With the growing use of high content screening (HCS) and analysis in drug
      discovery and systems biology, informatics has come to the forefront as a
      critical technology to effectively utilize the massive volumes of high content
      data and images being generated. Informatics technologies are required to
      transform HCS data and images into useful information and then into knowledge to
      drive decision making in an efficient and cost effective manner. In this chapter,
      we provide an overview of informatics tools and technologies for HCS, discuss
      some of the challenges of harnessing the huge and growing volumes of HCS data,
      and provide insight to help toward implementing or selecting, and utilizing a
      high content informatics solution to meet your organization's needs.

PMID- 16988411
TI  - Large-scale data management for high content screening.
AB  - High content screening (HCS) plays an important role in target selection in
      primary and secondary screening, but further developments in informatics and data
      management are needed for strategic implementation of HCS in the drug discovery
      process. An organization charter for the Research Informatics and Infrastructure
      Organization is described and is consists of four basic parts: Partner, Build
      Trust, Champion, and Core vs Noncore. The successful evolution of the charter
      over the last 5 yr is mapped using high-throughput screening and HCS data as an
      example. A future view of large-scale data management for the drug discovery
      process will incorporate all scientific information into multiple parameter type
      runs for many aspects of the science. This information will subsequently be
      aligned into a subset that an individual can digest and more easily choose the
      next appropriate steps.

PMID- 16988412
TI  - An integrated biomedical knowledge extraction and analysis platform: using
      federated search and document clustering technology.
AB  - High content screening (HCS) requires time-consuming and often complex iterative
      information retrieval and assessment approaches to optimally conduct drug
      discovery programs and biomedical research. Pre- and post-HCS experimentation
      both require the retrieval of information from public as well as proprietary
      literature in addition to structured information assets such as compound
      libraries and projects databases. Unfortunately, this information is typically
      scattered across a plethora of proprietary bioinformatics tools and databases and
      public domain sources. Consequently, single search requests must be presented to
      each information repository, forcing the results to be manually integrated for a
      meaningful result set. Furthermore, these bioinformatics tools and data
      repositories are becoming increasingly complex to use; typically they fail to
      allow for more natural query interfaces. Vivisimo has developed an enterprise
      software platform to bridge disparate silos of information. The platform
      automatically categorizes search results into descriptive folders without the use
      of taxonomies to drive the categorization. A new approach to information
      retrieval for HCS experimentation is proposed.

PMID- 16988413
TI  - Visualization of high content screening data.
AB  - Visualization is essential to the understanding of complex data derived from high
      content screening. It is necessary to present information in a way that captures
      patterns and trends in the data in order to answer specific questions while also
      providing a way to formulate new questions and hypothesis. Specific types of
      visualizations can provide information on the quality of the data, temporal, and
      spatial patterns of cellular response, cell phenotype, and the relationship to
      additional data such as the chemical structure of test compounds. Interacting
      with this data through linked visualizations and visual filtering facilitates
      exploration and hypothesis generation to better understand biological systems.

PMID- 16988414
TI  - Pathway mapping tools for analysis of high content data.
AB  - The complexity of human biology requires a systems approach that uses
      computational approaches to integrate different data types. Systems biology
      encompasses the complete biological system of metabolic and signaling pathways,
      which can be assessed by measuring global gene expression, protein content,
      metabolic profiles, and individual genetic, clinical, and phenotypic data. High
      content screening assays can also be used to generate systems biology knowledge.
      In this review, we will summarize the pathway databases and describe biological
      network tools used predominantly with this genomics, proteomics, and metabolomics
      data but which are equally as applicable for high content screening data
      analysis. We describe in detail the integrated data-mining tools applicable to
      building biological networks developed by GeneGo, namely, MetaCore and MetaDrug.

PMID- 16988415
TI  - Systems biology in cancer research: genomics to cellomics.
AB  - Cancers result from large-scale deregulation of genes that lead to cancer
      pathophysiologies such as increase proliferation, decreased apoptosis, increased
      motility, increased angiogenesis, and others. Genes that influence proliferation
      and apoptosis are particularly attractive as therapeutic targets. To identify
      genes that influence these phenotypes, we have developed simple and rapid methods
      to measure apoptosis and cell proliferation using high content screening with YO
      PRO-1 and anti-BrdU staining of BrdU pulsed cells, respectively.

PMID- 16988416
TI  - Target validation in drug discovery.
AB  - The process of target validation identifies and assesses whether a molecular
      target merits the development of pharmaceuticals for therapeutic application. The
      most valuable application of high content screening to target validation is at
      the early stages of the process when genetic methods (including RNA interference-
      RNAi) are being applied to many potential targets. At this stage both throughput
      and indepth analysis are required. This process is illustrated using various
      examples from the area of oncology target validation. The Akt signal transduction
      pathway is used to illustrate an efficient way of identifying HCS compatible
      reagents for use in assay development. RNAi transfection methods are discussed. A
      description is given of an HCS assay that simultaneously measures two nodes of
      the Akt pathway: Akt substrate phosphorylation and RPS6 phosphorylation. Another
      example of an assay measuring proliferation (DNA synthesis) and apoptosis
      (Histone H2B phosphorylation) within the same cell population is used to
      illustrate the combination of typical phenotypic assays.

PMID- 16988417
TI  - High content screening as a screening tool in drug discovery.
AB  - In most pharmaceutical and biotechnology companies there is a need to always
      improve the quality of lead candidates. This demand resulted in the use of cell
      based screening as a method of choice in drug discovery. High content screening
      (HCS) is multiplexed, functional cell-based screening. HCS can be used in all
      aspects of drug discovery as an engine for driving lead discovery. The biological
      applications of HCS have been implemented in research in signaling, cell shape
      changes and toxicology. HCS has enabled an insight in the cellular effects of our
      clinical candidates in multiple cellular phenomena like dual reporter assay,
      subcellular target translocation and cellular morphology. Discovery of
      therapeutic protein and small molecule converge on diseases in therapeutic areas
      such neurological disorders and autoimmune diseases. HCS is used for assay
      development, primary, secondary screening and toxicology testing. In this
      chapter, the use of HCS assays in drug discovery is described and highlight the
      necessary step to set-up successfully these assays for screening.

PMID- 16988418
TI  - Discovery of protein kinase phosphatase inhibitors.
AB  - Dynamic protein phosphorylation, a major cellular regulatory system, is tightly
      controlled by coordinating the reversible action of protein kinases and
      phosphatases. Recent evidence is consistent with sophisticated mechanisms that
      regulate both kinases and phosphatases in the cell. Dual specificity
      phosphatases, which act on phosphorylated serine, threonine, and tyrosine
      residues in proteins, are valid targets for drug discovery. Chemical
      complementation combines genetic manipulations with chemical biology and high
      content multiparametric analyses and was developed as a screening approach to
      discover protein phosphatase inhibitors. Using a dual specificity mitogen
      activated protein kinase phosphatase as an example, a detailed protocol,
      discussion of issues relating to data analysis, and high-throughput
      implementation of the chemical complementation approach to drug discovery is
      presented.

PMID- 16988419
TI  - High content translocation assays for pathway profiling.
AB  - This chapter describes the design and development of cell-based assays, in which
      quantitation of the intracellular translocation of a target protein--rather than
      binding or catalytic activity--provides the primary assay readout. These are
      inherently high content assays, and they provide feedback on cellular response at
      the systems level, rather than data on activities of individual, purified
      molecules. Multiple protein translocation assays can be used to profile cellular
      signaling pathways and they can play a key role in determination of mechanism of
      action for novel classes of compounds with therapeutic potential. This assay
      technology has developed from laboratory curiosity into main stream industrial
      research over the past decade, and its promise is beginning to be realized as
      data acquisition and analysis technology evolve to take advantage of the rich
      window into systems biology provided by translocation assays.

PMID- 16988420
TI  - In vitro cytotoxicity assessment.
AB  - The most frequent reason cited for withdrawal of an approved drug is toxicity,
      yet no simple solution exists to adequately predict such adverse effects.
      Compound prioritization and optimization during in vitro screening cascades need
      to be based on confidence, not only in efficacy and bioavailability, but also in
      safety. A wider number and diversity of potential molecular and cellular effects
      of compound interactions might affect safety than might affect efficacy or
      bioavailability. Accordingly, cytotoxicity assessment is less specific, more
      multiparametric, and extrapolatable with less certainty, unless there are
      specific safety signals indicated by the chemical structure or by precedents.
      Cytotoxicity assessments have been limited by their inability to measure
      multiple, mechanistic parameters that capture a wide spectrum of potential
      cytopathological changes. Assays with multiple parameters for key, multiple, and
      different features, such as in high content screening (HCS), are more predictive
      because they cover a wider spectrum of effects. Assays need to be applied to a
      large set of marketed drugs that produce toxicity by numerous and different
      mechanisms for assessment of correlation with human toxicity. This will enable
      determination of the concordance between in vitro and in vivo results.
      Multiparametric, live cell, prelethal cytotoxic HCS assays for assessing the
      potential of compounds for causing human toxicity address some of the limitations
      of traditional in vitro methods. Assays of this class were used to screen a
      library of drugs with varying degrees of toxicity and it was found that the
      sensitivity of the assays was 87%, whereas assay specificity was more than 90%,
      thereby minimizing false positives.

PMID- 16988421
TI  - Neurite outgrowth in retinal ganglion cell culture.
AB  - Retinal ganglion cells (RGC) are the projection neurons of the eye. The RGC is
      the primary cell type injured in a variety of diseases of the optic nerve,
      including glaucoma and optic neuritis. The most well-established extrinsic signal
      of RGC survival and axonal outgrowth is the neurotrophin brain-derived
      neurotrophic factor. An immunopurification system has been adapted in order to
      filter large enough quantities of RGCs from the mixed population of retinal
      neurons in order to perform high-throughput screening in a 96-well format. Using
      this assay, the screening of a combinatorial chemical library for compounds with
      a similar effect to brain-derived neurotrophic factor may be preformed. Follow-up
      validation studies are performed by evaluating for a dose-response relationship.

PMID- 16988422
TI  - An overview of C. elegans biology.
AB  - The establishment of Caenorhabditis elegans as a "model organism" began with the
      efforts of Sydney Brenner in the early 1960s. Brenner's focus was to find a
      suitable animal model in which the tools of genetic analysis could be used to
      define molecular mechanisms of development and nervous system function. C.
      elegans provides numerous experimental advantages for such studies. These
      advantages include a short life cycle, production of large numbers of offspring,
      easy and inexpensive laboratory culture, forward and reverse genetic
      tractability, and a relatively simple anatomy. This chapter will provide a brief
      overview of C. elegans biology.

PMID- 16988423
TI  - Comparative genomics in C. elegans, C. briggsae, and other Caenorhabditis
      species.
AB  - The genome of the nematode Caenorhabditis elegans was the first animal genome
      sequenced. Subsequent sequencing of the Caenorhabditis briggsae genome enabled a
      comparison of the genomes of two nematode species. In this chapter, we describe
      the methods that we used to compare the C. elegans genome to that of C. briggsae.
      We discuss how these methods could be developed to compare the C. elegans and C.
      briggsae genomes to those of Caenorhabditis remanei, C. n. sp. represented by
      strains PB2801 and CB5161, among others (1), and Caenorhabditis japonica, which
      are currently being sequenced.

PMID- 16988424
TI  - WormBase: methods for data mining and comparative genomics.
AB  - WormBase is a comprehensive repository for information on Caenorhabditis elegans
      and related nematodes. Although the primary web-based interface of WormBase
      (http:// www.wormbase.org/) is familiar to most C. elegans researchers, WormBase
      also offers powerful data-mining features for addressing questions of comparative
      genomics, genome structure, and evolution. In this chapter, we focus on data
      mining at WormBase through the use of flexible web interfaces, custom queries,
      and scripts. The intended audience includes users wishing to query the database
      beyond the confines of the web interface or fetch data en masse. No knowledge of
      programming is necessary or assumed, although users with intermediate skills in
      the Perl scripting language will be able to utilize additional data-mining
      approaches.

PMID- 16988425
TI  - C. elegans deletion mutant screening.
AB  - The methods used by the Caenorhabditis elegans Gene Knockout Consortium are
      conceptually simple. One does a chemical mutagenesis of wild-type C. elegans, and
      then screens the progeny of the mutagenized animals, in small mixed groups, using
      polymerase chain reaction (PCR) to identify populations with animals where a
      portion of DNA bounded by the PCR primers has been deleted. Animals from such
      populations are then selected and grown clonally to recover a pure genetic
      strain. We categorize the steps needed to do this as follows: (1) mutagenesis and
      DNA template preparation, (2) PCR detection of deletions, (3) sibling selection,
      and (4) deletion stabilization. These are discussed in detail in this chapter.

PMID- 16988426
TI  - Insertional mutagenesis in C. elegans using the Drosophila transposon Mos1: a
      method for the rapid identification of mutated genes.
AB  - One benefit of the nematode Caenorhabditis elegans as a model system is the ease
      to conduct forward genetic screens and to isolate mutants with phenotypes of
      interest. However, identifying the mutated genes requires positional cloning,
      which can be laborious and time consuming. Insertional mutagenesis with a
      heterologous transposon bypasses the mapping steps and expedites the process of
      identifying the mutated genes. The Drosophila transposon Mos1 can be mobilized in
      the C. elegans germline to cause mutations. Mutagenic insertions are subsequently
      localized within the genome using inverse polymerase chain reaction. The
      mutagenicity of this technique is roughly one order of magnitude lower than
      chemical mutagens. However, the molecular identification of the mutated genes is
      extremely rapid. Therefore, before using Mos1-mediated mutagenesis, one must
      evaluate the trade-off between time spent screening for mutants vs time spent
      mapping and rescuing a mutation.

PMID- 16988427
TI  - Single-nucleotide polymorphism mapping.
AB  - Single-nucleotide polymorphism (SNP) mapping is the easiest and most reliable way
      to map genes in Caenorhabditis elegans. SNPs are extremely dense and usually have
      no associated phenotype, making them ideal markers for mapping. SNP mapping has
      three steps. First, recombinant mutant animals are generated over a polymorphic
      strain (usually CB4856) using standard genetic techniques. Second, the genotype
      of these animals at SNP loci is determined using one of a variety of SNP
      detection technologies. Third, linkage between the mutant and one or more SNPs is
      used to position the mutant on the chromosome relative to the SNPs. This chapter
      presents a detailed procedure for generating recombinant animals, for assaying
      SNPs using restriction enzymes, and for analyzing mapping data.

PMID- 16988428
TI  - Creation of transgenic lines using microparticle bombardment methods.
AB  - Introduction of exogenous DNA into Caenorhabditis elegans is important for
      examining the expression of altered or reporter gene constructs, rescuing mutant
      genes, and studying gene function in vivo. Until recently, germ-line injection
      was the most commonly used method for transforming C. elegans strains. This
      chapter describes four different microparticle bombardment methods used to
      transform C. elegans with exogenous DNA. We include a discussion of the
      advantages and disadvantages of using microparticle bombardment for
      transformation, list cotransformation markers that have been used successfully in
      microparticle bombardment experiments, and discuss transformation efficiency.

PMID- 16988429
TI  - Construction of plasmids for RNA interference and in vitro transcription of
      double-stranded RNA.
AB  - Double-stranded RNA (dsRNA)-induced gene silencing in Caenorhabditis elegans
      involves the manufacture and delivery of defined sequences of dsRNA to the
      organism, followed by a careful monitoring for loss-of-function phenocopies in
      treated animals. In this chapter, we describe how to generate DNAs that can be
      used as templates for transcription of dsRNA.

PMID- 16988430
TI  - Delivery methods for RNA interference in C. elegans.
AB  - This chapter describes four methods for delivery of double-stranded RNA to
      Caenorhabditis elegans (injection, feeding, soaking, and in vivo delivery), and
      suggests schemes that should facilitate detection of specific gene silencing.

PMID- 16988431
TI  - Functional genomic approaches in C. elegans.
AB  - The nematode Caenorhabditis elegans is an extraordinarily powerful model organism
      for the application of functional genomic approaches. Two such approaches, whole
      genome microarray analysis and genome-wide RNA interference (RNAi)-mediated
      phenotypic screening, are highly advanced and can be used by virtually any
      laboratory to study biological processes of interest. Using studies of the
      osmotic stress response in C. elegans as an example, this chapter describes
      methods for conducting whole genome microarray experiments and for carrying out
      genome-wide reverse-genetic screens using a commercially available C. elegans
      bacterial RNAi feeding library. Both approaches are complimentary and can be used
      to rapidly gain genome-wide insights into the genes and gene networks controlling
      specific physiological processes.

PMID- 16988432
TI  - Assays for toxicity studies in C. elegans with Bt crystal proteins.
AB  - Caenorhabditis elegans is well suited for toxicological studies owing to its
      established biology, short generation time, large brood size, and readily
      scorable life traits. Quantitative parameters of C. elegans that can be assayed
      include growth, size, progeny production, behavior, and mortality. Qualitative
      parameters of toxicity, such as changes in appearance or movement, can also be
      determined. This chapter describes four assays we have used for analyzing the
      toxic effects of Bacillus thuringiensis crystal proteins toward C. elegans. The
      assays are quantitative growth measurement, brood size measurement, and
      determination of lethal concentration, as well as a qualitative health assay
      based on worm appearance. Although these assays are described for crystal
      proteins, the approaches are suited for the studies of other toxins with C.
      elegans.

PMID- 16988433
TI  - Fluorescent reporter methods.
AB  - The identification and cloning of the green fluorescent protein (GFP) from
      jellyfish marks the beginning of a new era of fluorescent reporters. In
      Caenorhabditis elegans, genetically encoded markers like the fluorescent proteins
      of the GFP family became the reporter of choice for gene expression studies and
      protein localization. The small size and transparency of the worm allows the
      visualization of in vivo dynamics, which increases the number of potential
      applications for fluorescent reporters tremendously. In combination with
      subcellular tags, GFP can be used to label subcellular structures like synapses
      allowing novel approaches to study developmental processes like synapse
      formation. Other fluorescent labels like small organic dyes, which are in
      widespread use in cell culture systems, are rarely used in C. elegans owing to
      difficulties in applying these labels through the impenetrable cuticle or
      eggshell of the animal. A notable exception is the use of lipophilic dyes, which
      are taken up by certain sensory neurons in the intact animal and can be
      introduced into the embryo after puncturing of the egg shell. This chapter covers
      the use of fluorescent dyes and fluorescent proteins in C. elegans. Emphasis is
      placed on microscopic techniques including wide field and confocal microscopy as
      well as time-lapse recordings. The use of fluorescent proteins as transgenic
      markers and image processing of fluorescence images are briefly discussed.

PMID- 16988434
TI  - Electrophysiological analysis of neuronal and muscle function in C. elegans.
AB  - The nematode Caenorhabditis elegans provides numerous experimental advantages for
      the identification and characterization of genes required for the function of the
      nervous system. These advantages include forward and reverse genetic
      tractability, a relatively simple body plan with an invariant cellular lineage,
      and a fully sequenced and well-annotated genome. However, one limitation of C.
      elegans is the relative scarcity of electrophysiological data from excitable
      cells. To address this limitation, high-resolution cellular techniques for
      probing the roles of specific gene products in the C. elegans nervous system have
      been recently developed. This chapter will provide an overview of the technical
      requirements for patch-clamp electrophysiological analysis of C. elegans neurons
      and muscle cells, as well as provide some illustrative examples of insights
      gained from the pairing of electrophysiological techniques with molecular and
      genetic analysis.

PMID- 16988435
TI  - Sperm and oocyte isolation methods for biochemical and proteomic analysis.
AB  - Caenorhabditis elegans gonad is a simple model to investigate molecular
      mechanisms that regulate fundamental cell and developmental processes. The
      strength of the model is that C. elegans is amenable to genetic manipulation. The
      complete genome sequence, advances in mass spectrometry, and RNA-mediated
      interference (RNAi) are now providing a technical infrastructure that complements
      biochemical and proteomic approaches. This chapter describes simple methods for
      sperm and oocyte isolation and gonad liberation that can be performed routinely
      in the lab, without expensive equipment. These methods are ideal for biochemical
      and proteomic applications, including those aiming to identify proteins based on
      affinity or biological activity. Germline mRNA expression profiles, RNAi feeding
      clones, and Gateway-engineered ORFeome vectors are available to help validate
      experimental results.

PMID- 16988436
TI  - Preservation of C. elegans tissue via high-pressure freezing and freeze
      substitution for ultrastructural analysis and immunocytochemistry.
AB  - High-pressure freezing (HPF) is capable of converting liquid water, to a depth of
      approx 0.6 mm, into amorphous ice nearly instantaneously. At midbody, an adult
      Caenorhabditis elegans hermaphrodite approaches its widest girth of approx 0.1
      mm. In theory, an entire living adult animal can be physically immobilized
      instantly in amorphous ice by HPF, thus, providing a unique opportunity to
      examine cellular architecture with exquisite spatial preservation. The following
      chapter will discuss, in detail, procedures for freezing C. elegans under high
      pressure, for embedding frozen samples in resin after a freeze-substitution step,
      and for the postembedding immunogold labeling of proteins contained within thin
      sections of embedded animals. These protocols enable high-resolution analysis of
      both morphological features and molecular domains within most tissues of C.
      elegans.

PMID- 16988437
TI  - Intracellular pH measurements in vivo using green fluorescent protein variants.
AB  - Whether by patch-clamp techniques or the use of fluorescent vital dyes,
      measurements of transepithelial ion flux in mammals are limited by cell
      accessibility. Furthermore, redundant functions and complex regulatory mechanisms
      can mask loss-of-function phenotypes through compensatory mechanisms. In this
      chapter, we present a technique whereby the optically transparent nematode
      Caenorhabditis elegans, engineered to express a fluorescent pH indicator protein,
      can be used to study how intracellular pH (pHi) fluctuates in response to
      environmental and/or experimental challenge. By using a live whole animal model,
      systemic, and even behavioral relationships to individual cellular pHi can be
      inferred. In combination with dye loading of excised or cultured cells, this
      technique also provides a powerful means of contrasting these relationships to
      biophysical measurements of ion flux.

PMID- 16988438
TI  - Automated imaging of C. elegans behavior.
AB  - Automated systems for recording and analyzing behavior have many applications for
      the study of neurobiology in Caenorhabditis elegans. In particular, machine-based
      approaches allow for precise quantitative definitions of behavioral phenotypes
      that have traditionally been subjectively described by individual observers.
      Automated systems also facilitate the analysis of behaviors that occur over long
      time scales or are difficult to detect by eye. Here we describe the detailed
      methodology for the use of one recently described automated tracking system for
      C. elegans. These protocols make it possible to measure a wide range of
      parameters related to the morphology, body posture, and locomotion patterns of
      individual wild-type and mutant nematodes.

PMID- 16988440
TI  - In vitro culture of C. elegans somatic cells.
AB  - Because of technical hurdles, large-scale cell culture methods have not been
      widely exploited until recently for the study of Caenorhabditis elegans.
      Culturing differentiated cells from larvae and adult worms is probably not
      technically feasible because of difficulties in removing the animal's cuticle and
      dissociating cells. In contrast, large numbers of developing embryo cells can be
      isolated relatively easily. When placed in culture, embryo cells undergo terminal
      differentiation within 24 h. Cultured embryo cells have been used recently to
      characterize ion channel function and regulation and to determine cell specific
      gene expression patterns. This chapter will provide a detailed description of the
      methods for isolating and culturing C. elegans embryo cells.

PMID- 16988441
TI  - Techniques for analysis, sorting, and dispensing of C. elegans on the COPAS flow
      sorting system.
AB  - The COPAS Biosorter is a flow cytometer designed to accommodate large objects the
      size of Caenorhabditis elegans. This instrumentation brings high-speed automated
      analysis and sorting to this small model organism. The Biosort system optically
      analyzes and sorts living multicellular organisms on the basis of fluorescent
      protein expression patterns and other optical signatures, at rates up to about
      100 organisms per second. The Biosort is capable of fluorescently analyzing and
      sorting multicellular organisms that are many-fold larger than single cells.
      Animals pass through a laser beam focused to the center of the flow cell. This
      beam is narrower than the animal so that multiple measurements are made per
      animal, which means that the organism is optically scanned along its long axis as
      it flows. Stable laminar flow in the flow cell acts to orientate the animal with
      the flow stream. Fluorescent locations along the axis of the animal are
      sequentially excited as the organism flows through the line of focus. The
      fluorescent properties of commonly used reagents in the research field allow the
      user to detect fluorescent protein expression, lectin and antibody binding, and
      autofluorescence. The ability to dispense organisms as they emerge from the flow
      cell allows for the collection of those organisms that have certain optical
      properties defined by the researcher. Also, dispensing allows for the precise
      distribution of specific numbers of animals for analysis that can vary with
      organism numbers.

PMID- 16988439
TI  - Intracellular Ca2+ imaging in C. elegans.
AB  - Optical methods provide a noninvasive way to monitor calcium transients in
      Caenorhabditis elegans. Imaging techniques are particularly appealing in C.
      elegans because worms are optically transparent and can be imaged while fully
      intact. Furthermore, a variety of genetically encoded calcium indicators are
      available that can be targeted to cells of interest with appropriate tissue
      specific promoters. Here, we describe a specific protocol, suitable for
      monitoring neuronal activity, for rapid calcium imaging in C. elegans using the
      cameleon indicator. Notes are provided to assist with adapting this protocol for
      use with other indicators and slower time scales.

PMID- 16988442
TI  - DNA vaccine design.
AB  - The purpose of this chapter is to present basic strategies for the construction
      of DNA vaccines. This chapter discusses considerations relevant to the selection
      of a target gene, construction of a DNA expression vector for use as a vaccine,
      and molecular modifications of the vector to improve protein expression and to
      augment immunogenicity.

PMID- 16988443
TI  - Design of plasmid DNA constructs for vaccines.
AB  - For more than three decades, plasmids have been widely used in the biotechnology
      arena. Historically, they have been most often employed for the expression of
      heterologous proteins in a variety of microorganisms. More recently, plasmids
      have been used as vectors for the delivery of antigen encoding genes in order to
      elicit immune responses in higher order animals. In this chapter, we discuss
      methods for constructing vectors with this unique purpose. Considerations for
      choosing the replicon, antigen, expression elements, and host cells are discussed
      within the context of developing a commercially viable vaccine vector.

PMID- 16988444
TI  - Vaccination with messenger RNA.
AB  - As an alternative to DNA-based vaccines, messenger RNA (mRNA)-based vaccines
      present additional safety features: no persistence, no integration in the genome,
      no induction of autoantibodies. Moreover, mRNA which are generated by in vitro
      transcription, are easy to produce in large amounts and very high purity. This
      feature facilitates the good manufacturing practices process and guaranties batch
      to-batch reproducibility. Vaccination can be achieved by several delivery methods
      including direct injection of naked mRNA, injection of mRNA encapsulated in
      liposomes Gene Gun delivery of mRNA loaded on gold beads or in vitro transfection
      of the mRNA in cells followed by re-injection of the cells into the patients. Two
      of these technologies are being evaluated in human clinical trials: (1) in vitro
      mRNA-transfection of dendritic cells to be adoptively transferred and (2) direct
      injection of globin-stabilized mRNA. This chapter describes the production of
      mRNA and the preparation of the two types of mRNA-based vaccines tested in
      humans.

PMID- 16988445
TI  - A stress protein-facilitated antigen expression system for plasmid DNA vaccines.
AB  - In DNA vaccination, an exciting new immunization technique with potential
      applications in clinical medicine, expression plasmid DNA containing antigen
      encoding sequences cloned under heterologous promoter control are delivered by
      techniques that lead in vivo to antigen expression in transfected cells. DNA
      vaccination efficiently primes both humoral and cellular immune responses. We
      developed a novel expression system for DNA vaccines in which a fusion protein
      with a small, N-terminal, viral DnaJ-like sequence (J domain) is translated in
      frame with C-terminal antigen-encoding sequences. The J domain stable bind to
      constitutively expressed, cytosolic stress protein hsp73 and triggers
      intracellular accumulation of antigen/hsp73 complexes. The system supports
      enhanced expression of chimeric antigens of >800 residues in length in
      immunogenic form. A unique advantage of the system is that even unstable or toxic
      proteins (or protein domains) can be expressed. We describe the design of DNA
      vaccines expressing antigens with a stress protein-capturing domain and
      characterize the immunogenicity of the antigens produced by this expression
      system.

PMID- 16988446
TI  - In vitro assay of immunostimulatory activities of plasmid vectors.
AB  - DNA vaccination represents a novel and potentially important approach to induce
      immune responses against protein antigens. In this approach, the vaccine is a
      plasmid DNA vector that can be taken up by cells to produce a protein, encoded by
      the vector, to be targeted for the induction of humoral or cellular responses.
      Although the intracellular production of the antigen may promote responses, the
      vectors themselves may display adjuvant activity because of their intrinsic
      immunostimulatory properties. These properties reflect sequence motifs, centering
      on an unmethylated CpG dinucleotide, which can trigger the TLR9 pattern
      recognition receptor. As shown by studies in vitro, plasmid DNA can stimulate B
      cells, macrophages, and dendritic cells, and trigger a broad range of pro
      inflammatory responses. Because this stimulation results from common sequence
      motifs, the activity of a plasmid vector can be assessed by the in vitro assay of
      a limited number of responses, including proliferation of B cells as well as
      production of cytokines by macrophages or dendritic cells.

PMID- 16988447
TI  - Delivery of DNA vaccines using electroporation.
AB  - Although DNA immunization remains a very attractive method to induce immunity to
      a variety of pathogens, the transfection efficiency is still relatively low. This
      is especially true in species other than mice. One way of improving this
      efficiency is to temporarily permeabilize the cells to allow cellular uptake of
      DNA plasmids. One way to permeabilize cells is by electroporation. The current
      report describes some of the parameters for optimizing electroporation for
      enhancing the level of gene expression. A clear concern is balancing the plasmid
      uptake with cellular or tissue damage. Techniques are described to achieve this
      goal.

PMID- 16988448
TI  - Needle-free injection of DNA vaccines: a brief overview and methodology.
AB  - The development of needle-free injection originally stemmed from a general
      apprehension of needle injections, disease transmission by accidental needle
      sticks, and the need for effective mass immunization. Naked DNA vaccines, as
      attractive and universal as they appear, have not produced robust immune
      responses in test systems. However, proof of principle for DNA vaccines has been
      validated with a number of vaccine candidates in a variety of test systems, and
      the concept of DNA vaccines as a generic platform for vaccines still remains
      viable and attractive. Many avenues are being explored to enhance the
      immunogenicity of DNA vaccines. The easiest and most straightforward approach
      that can be quickly transitioned to a clinical trial setting is vaccine delivery
      by a needle-free jet injector. This approach has shown much potential in a number
      of cases and should become the lead method for enhancing DNA vaccines. This
      approach requires no additional development, and with an expanding market and
      willingness from jet injector manufacturers to produce prefilled syringes, the
      technique should become feasible for larger phase II/phase III trials.

PMID- 16988449
TI  - Needle-free delivery of veterinary DNA vaccines.
AB  - Currently, there are a number of obstacles barring effective immunization of
      large animal species with DNA-based vaccines. Generally, large concentrations of
      DNA and multiple doses are required before an effective immune response is
      detected. To overcome these impediments we have developed approaches to deliver
      the plasmids via needle-free methods, which have been shown to be more effective
      than traditional needle and syringe methods. Furthermore, we will describe the
      delivery of vaccines to mucosal surfaces. The procedures described will use sheep
      and cattle as model veterinary species.

PMID- 16988450
TI  - Surface-modified biodegradable microspheres for DNA vaccine delivery.
AB  - Encapsulating DNA within degradable delivery vehicles such as micro- or
      nanospheres provides an effective way to protect the DNA from the surrounding
      environment prior to delivery. The ability to target these vehicles directly to
      the cell type of interest provides a way to enhance the overall efficiency of DNA
      delivery. One means of highly specific cell targeting is through the addition to
      the vehicle surface of ligands that bind specifically to receptors on the surface
      of the targeted cell type. Covalent conjugation of ligands to the surface of
      degradable delivery vehicles can be difficult, as the most commonly used vehicle
      formulations use materials selected for their general chemical inertness. This
      chapter describes methods for overcoming this, enabling encapsulation of DNA
      within degradable microspheres made of a commonly used biomaterial and then
      covalently conjugating ligands to the surface of these microspheres.

PMID- 16988451
TI  - A dendrimer-like DNA-based vector for DNA delivery: a viral and nonviral hybrid
      approach.
AB  - DNA can be used as a generic delivery vector in addition to its genetic role as a
      antigen expression vector. This is inspired in part by the fact that DNA
      molecules are true polymers. Surprisingly, DNA molecules have not been used as a
      delivery vector material. This is probably due to the fact that almost all DNA
      have only two shapes: linear or circular. This chapter details our efforts in
      fabricating highly branched dendrimer-like DNA (DL-DNA) that may serve as a
      multivalent DNA delivery vector. Just like chemical dendrimers, DL-DNA is multi
      valent and monodisperse. However, unlike traditional chemical dendrimers, DL-DNA
      is much larger (~100 nm, generation 4) and can be designed to be nonsymmetric as
      well. Most importantly, DL-DNA possesses two unique properties: anisotropicity
      and biodegradability, making multiple, specific conjugations of viral peptides
      possible. Our method suggests that viral-pep-tide conjugated DL-DNA vectors can
      deliver genes into cells without any other transfection reagents. This viral
      nonviral hybrid system can be further tailored to specific cells by conjugating
      specific ligands. We believe that such a DL-DNA-based, viral, and nonviral hybrid
      assembly will provide a new platform for drug delivery in general and gene
      delivery in particular.

PMID- 16988452
TI  - Identification of compartments involved in mammalian subcellular trafficking
      pathways by indirect immunofluorescence.
AB  - A characteristic of a successful DNA vaccine is its trafficking to the nucleus
      where it can be transcribed. Plasmid DNA coupled to a delivery vector must enter
      the cell, navigate its way through endocytic compartments, and ultimately reach
      the nucleus. Currently, the precise pathway taken by plasmid DNA is not clear.
      Understanding how plasmid DNA interacts with the cell and which path it follows
      to reach the nucleus will aid in the rational design of improved delivery
      vectors. Achieving this goal requires a means by which to monitor the subcellular
      trafficking of plasmid DNA and delivery vectors. Presented here are methods for
      identifying various endocytic compartments involved in mammalian subcellular
      trafficking pathways using indirect immunofluorescence. Together with labeled
      delivery vectors and/or plasmid DNA, these methods can aid in the understanding
      of the trafficking pathways involved in DNA delivery, and contribute to the
      rational design of more efficient delivery vectors.

PMID- 16988453
TI  - Adjuvant properties of CpG oligonucleotides in primates.
AB  - Unlike mammalian DNA, bacterial, plasmid, and synthetic DNA containing
      unmethylated CpG dinucleotides in specific sequence contexts are recognized by
      the Toll-like receptor 9 expressed by B cells and plasmacytoid dendritic cells,
      and trigger the activation of the innate and adaptive immune system. Upon
      signaling, CpG DNA induces B cells, natural killer cells, macrophages, and
      dendritic cells to proliferate, differentiate, take up, and present antigen and
      secrete a variety of immunoglobulins, chemokines, and predominantly Th1-type
      cytokines. Preclinical studies in mice and primates show that DNA sequences
      containing CpG motifs can selectively promote cellular and/or humoral immune
      responses in vivo. Early results from ongoing clinical studies indicate that CpG
      oligonucleotides (ODN) are well tolerated and improve the immune response to
      microbial vaccines. This work examines the progress in utilizing CpG ODN as
      adjuvants in conventional and DNA vaccines.

PMID- 16988454
TI  - Complexes of DNA vaccines with cationic, antigenic peptides are potent,
      polyvalent CD8(+) T-cell-stimulating immunogens.
AB  - A priority in current vaccine research is the development of multivalent vaccines
      that support the efficient priming of long-lasting CD8(+) T-cell immunity. We
      developed a novel vaccination strategy that used synthetic, cationic (positively
      charged), and antigenic peptides complexed to negatively charged nucleic acids:
      antigenic, major histocompatibility complex-class I-binding epitopes fused with a
      cationic sequence derived from the HIV tat protein (tat50-57: KKRRQRRR) were
      mixed with nucleic acids (e.g., CpG-containing oligonucleotides) to
      quantitatively form peptide/nucleic acid complexes. The injection of these
      complexes efficiently primed long-lasting, specific CD8(+) T-cell immunity of
      high magnitude. This chapter describes a novel strategy to codeliver complexes of
      cationic/antigenic peptides bound to antigen-encoding plasmid DNA vaccines in a
      way that enhances the immunogenicity of both components for T cells.

PMID- 16988455
TI  - Prime-boost strategies in DNA vaccines.
AB  - Induction of HIV-specific T-cell responses by vaccines may facilitate efficient
      control of HIV replication. Plasmid DNA vaccines and recombinant fowlpox virus
      (rFPV) vaccines are promising HIV-1 vaccine candidates, although delivering
      either vaccine alone may be insufficient to induce sufficient T-cell responses. A
      consecutive immunization strategy, known as "prime-boost," involving priming with
      DNA and boosting with rFPV vaccines encoding multiple common HIV antigens, is
      used to induce broad and high-level T-cell immunity and ameliorate AIDS in
      macaques. This vaccine strategy is proceeding to clinical trials. This chapter
      describes the use of prime-boost vaccines to induce T-cell responses against HIV
      1 and protective immunity against AIDS in macaques. Methods for the construction
      of the vaccines, the use of animal models, and the detection of immune responses
      are described.

PMID- 16988456
TI  - Modifying professional antigen-presenting cells to enhance DNA vaccine potency.
AB  - DNA vaccines have emerged as a potentially important form of vaccination in the
      control of infectious diseases and cancers. It is now clear that professional
      antigen-presenting cells (APCs), such as dendritic cells (DCs) play important
      roles in generating humoral and cell-mediated antigen-specific immune responses
      by DNA vaccination. Continuing progress in our understanding of how professional
      APCs uptake DNA, process and present the antigens encoded by DNA vaccines to
      activate B- and T-cell-mediated immune responses in vaccinated individuals
      provides a framework from which to design more effective DNA vaccines. Advances
      in molecular biology technology allow DNA to be easily manipulated and make the
      implementation of novel DNA vaccine strategies possible. This review discusses
      strategies employing molecular biology technology to improve DNA vaccine potency.
      These approaches include strategies to increase the numbers of antigen-expressing
      DCs, strategies to enhance MHC class I and/or II presentation of the encoded
      antigen and strategies to prolong the life of antigen-expressing DCs to enhance
      DNA vaccine potency. We will also discuss the methodology involved in DNA vaccine
      development targeting human papillomavirus oncogenic protein E7.

PMID- 16988457
TI  - Replicase-based DNA vaccines for allergy treatment.
AB  - Replicase-based vaccines were introduced to overcome some of the deficiencies of
      conventional DNA- and RNA-based vaccines, including poor efficiency and low
      stability. At ultra-low doses, these alphavirus-derived vectors elicit cellular
      as well as humoral immune responses. Additionally, replicase-based vectors induce
      "self-removal" of the vaccine via apoptosis of transfected cells. This chapter
      describes the construction of a replicon-based DNA vaccine vector from
      commercially available plasmids. We present protocols for monitoring cellular
      immune responses following replicase-based immunization including measurement of
      allergen-specific proliferation of splenocytes, ELISPOT, a FACS-based cytokine
      secretion assay providing information about T-helper subsets, and a cytokine
      fluorescent bead immunoassay.

PMID- 16988458
TI  - Immunological responses of neonates and infants to DNA vaccines.
AB  - In some parts of sub-Saharan Africa, it is believed that most of the deaths
      attributed to malaria occur in infants. For this and other logistical reasons, if
      a malaria vaccine is developed and licensed, it will have to be administered to
      neonates or young infants, when they have maternally acquired antibodies against
      malaria parasite proteins. Pre-erythrocytic malaria vaccines in development rely
      on CD8(+) T cells as immune effectors, yet some studies indicate that neonates do
      not mount optimal CD8+ T-cell responses. We report that BALB/c mice first
      immunized as neonates (7 d) with a Plasmodium yoelii circumsporozoite protein
      (PyCSP) DNA vaccine mixed with a plasmid expressing murine granulocyte macrophage
      colony stimulating factor (DG) and boosted at 28 d with pox virus expressing
      PyCSP were protected (93%) as well as mice immunized entirely as adults (70%).
      Like adults, protection was dependent on CD8(+) T cells and accompanied by
      excellent anti-PyCSP interferon-gamma and cytotoxic T-lymphocyte responses. Mice
      born of immune mothers (previously exposed to P. yoelii parasites or immunized
      with the same vaccine given to the neonates) were also protected and had
      excellent T-cell responses. These data support assessment of this immunization
      strategy in neonates/young infants in areas where malaria exacts the greatest
      toll.

PMID- 16988459
TI  - DNA vaccines for allergy treatment.
AB  - The ability of DNA vaccines to stimulate Th1 type reactions has rendered them a
      promising tool for immunotherapy of type I allergy. In this chapter, we describe
      strategies for up-to-date anti-allergic DNA-based immunization. This includes
      codon optimization of allergen genes, CpG-enrichment of plasmid vectors for
      enhanced Th1-bias, and the creation of hypoallergenic DNA vaccines either by gene
      fragmentation or by forced ubiquitination, both reducing the risk of side
      effects. Also, detailed protocols for plasmid DNA purification, intradermal
      immunization, and subcutaneous allergen sensitization are provided. Read-out
      systems presented in this chapter are focused on humoral immune responses and
      comprise measurement of mediator release from basophils induced by functional IgE
      and an ELIS A protocol based on chemiluminescence technology.

PMID- 16988460
TI  - Protection from autoimmunity by DNA vaccination against T-cell receptor.
AB  - T-lymphocytes are essential participants of adaptive immunity, essential for
      cellular and humoral recognition of foreign antigens. In pathogenic situations T
      cells may, however, also recognize self-antigens, causing detrimental autoimmune
      responses that ultimately lead to autoimmune disease. Experimental autoimmune
      encephalomyelitis (EAE) is a murine model for the autoimmune disease multiple
      sclerosis, in which T cells invade the central nervous system and destroy the
      myelin sheath around neuronal axon fibers. In some EAE systems, the sequence of
      the alpha- or beta-chains of the pathogenic T-cell receptor is known and makes it
      possible to induce an immune response that eliminates these self-specific T
      cells. Herein we describe a method, using DNA vaccination that allows induction
      of such an immune response to protect mice from the development of EAE.

PMID- 16988461
TI  - The use of bone marrow-chimeric mice in elucidating immune mechanisms.
AB  - DNA vaccines hold promise for generating protective immunity against a wide
      variety of pathogens. Understanding the mechanism by which vaccine-encoded
      antigens are processed and presented to naive lymphocytes in the host is critical
      for rational design of efficacious vaccines. This chapter provides practical
      guide in making irradiation-induced bone marrow chimeric mice, which can be used
      to dissect a variety of aspects of antigen presentation by the hematopoietic vs
      nonhematopoietic compartments.

PMID- 16988462
TI  - A simple method for the production of plasmid DNA in bioreactors.
AB  - The need for large quantities of purified plasmid DNA has increased as the
      applications of DNA vaccines continue to expand. This chapter describes a simple,
      scaleable procedure based on the fed-batch cultivation of various Escherichia
      coli clones, which can be easily implemented and scaled-up to large bioreactors.
      Although some clones may require minor modifications to the feeding strategy, in
      general, this procedure, implemented as described, is likely to support the
      production of milligram to gram quantities of plasmid DNA.

PMID- 16988463
TI  - Practical methods for supercoiled pNDA production.
AB  - Increased demand for plasmid DNA (pDNA) to be produced to tighter and more
      exacting specifications, even for early preclinical work, has led to many
      researchers and manufacturers reevaluating their production methodologies. This
      chapter is intended to offer realistic methods that may be employed by those
      wishing to purify between 100 and 200 mg of pDNA in-house based on availability
      of equipment and other resources. This scale of production typically requires a
      compromise between techniques used with gravity-flow or vacuum devices and
      intermediate scale column chromatography. The methodologies described in most
      instances are unit processes that can be adapted into an appropriate scheme given
      such considerations as the desired purity level or the quality of the feedstock.

PMID- 16988464
TI  - Production of plasmid DNA in industrial quantities according to cGMP guidelines.
AB  - Qiagen offers a unique technology for plasmid manufacturing, working reliably for
      every parent plasmid. The process steps such as strain and clone selection, and
      fermentation optimization ensure optimal plasmid DNA yield and quality in the
      starting material. Master Cell Bank and Working Cell Bank manufacturing is then
      performed under cGMP conditions. A high-yield, low mechanical stress alkaline
      lysis procedure, followed by a proprietary endotoxin-removal step and anion
      exchange chromatography ensures consistently high plasmid DNA quality. The
      material undergoes stringent quality control tests and is accompanied by a
      comprehensive quality control report and a documentation package for regulatory
      filing. The following chapter describes the necessary steps such as host cell
      selection, growth conditions, downstream processing, and quality assurance and
      control.

PMID- 16988465
TI  - Large-scale, nonchromatographic purification of plasmid DNA.
AB  - A large-scale approach to the purification of plasmid DNA has been developed that
      overcomes many of the limitations of current chromatography-based processes. The
      process consists of a scaleable lysis using recombinant lysozyme and a rapid
      heating and cooling step followed by a selective precipitation with
      cetyltrimethylammonium bromide (CTAB). Calcium silicate batch adsorption is then
      utilized to remove residual genomic DNA, linear plasmid, open circular plasmid,
      endotoxin, detergents, and proteins. Finally, a concentration and diafiltration
      step utilizing ultrafiltration and a terminal sterile filtration complete the
      process. The final product exceeds the requirements for clinical-grade plasmid
      DNA, and the process has been scaled up to yield an average of 18 +/- 4 g (over
      five lots) of pharmaceutically pure plasmid DNA per 140 L of lysate (from approx
      1.3 kg Escherichia coli dry cell weight).

PMID- 16988467
TI  - Paving the road towards non-invasive molecular imaging.

PMID- 16988466
TI  - Assuring the quality, safety, and efficacy of DNA vaccines.
AB  - Scientists in academia whose research is aimed at the development of a novel
      vaccine or approach to vaccination may not always be fully aware of the
      regulatory process by which a candidate vaccine becomes a licensed product. It is
      useful for such scientists to be aware of these processes, as the development of
      a novel vaccine could be problematic as a result of the starting material often
      being developed in a research laboratory under ill-defined conditions. This
      chapter examines the regulatory process with respect to the development of a DNA
      vaccine. DNA vaccines present unusual safety considerations which must be
      addressed during nonclinical safety studies, including adverse immunopathology,
      genotoxicity through integration into a vaccinee's chromosomes and the potential
      for the formation of anti-DNA antibodies.

PMID- 16988468
TI  - Non-invasive in vivo imaging in small animal research.
AB  - Non-invasive real time in vivo molecular imaging in small animal models has
      become the essential bridge between in vitro data and their translation into
      clinical applications. The tremendous development and technological progress,
      such as tumour modelling, monitoring of tumour growth and detection of
      metastasis, has facilitated translational drug development. This has added to our
      knowledge on carcinogenesis. The modalities that are commonly used include
      Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission
      Tomography (PET), bioluminescence imaging, fluorescence imaging and multi
      modality imaging systems. The ability to obtain multiple images longitudinally
      provides reliable information whilst reducing animal numbers. As yet there is no
      one modality that is ideal for all experimental studies. This review outlines the
      instrumentation available together with corresponding applications reported in
      the literature with particular emphasis on cancer research. Advantages and
      limitations to current imaging technology are discussed and the issues concerning
      small animal care during imaging are highlighted.

PMID- 16988469
TI  - Detection of tumor cells in bone marrow, peripheral blood and lymph nodes by
      automated imaging devices.
AB  - The presence of tumor cells in bone marrow, peripheral blood and lymph nodes has
      proven its clinical and prognostic value. Since the frequency of these cells in
      bone marrow and blood is sometimes as low as 1 per million and due to the fact
      that for the analysis of lymph nodes many sectioning levels have to be analyzed,
      automated imaging devices have been suggested as an useful alternative to
      conventional manual screening of specimens. The aim of this paper is to review
      the performance of current equipment that is commercially available, based on
      literature published so far. Requirements for introducing this equipment for
      routine clinical practice are discussed.

PMID- 16988470
TI  - Detection of HER2 amplification in breast carcinomas: comparison of Multiplex
      Ligation-dependent Probe Amplification (MLPA) and Fluorescence In Situ
      Hybridization (FISH) combined with automated spot counting.
AB  - In this study the detection of HER2 gene amplification was evaluated using
      Fluorescence In Situ Hybridization (FISH; PathVysion) in comparison with
      Multiplex Ligation-dependent Probe Amplification (MLPA), a PCR based technique.
      These two methods were evaluated on a series of 46 formalin fixed paraffin
      embedded breast carcinomas, previously tested for protein overexpression by
      HercepTest (grouped into Hercep 1+, 2+ and 3+). HER2 gene amplification (ratio >
      or =2.0) by FISH was found in 9/10, 10/30 and 0/6 in IHC 3+, 2+ and 1+/0 cases,
      respectively. Digitalized automated spot counting performed with recently
      developed CW4000 CytoFISH software was 100% concordant with manual FISH scoring.
      Using MLPA 18/46 samples showed a clear HER2 amplification. Comparing MLPA and
      IHC showed the same results as for FISH and IHC. All but one FISH positive cases
      (18/19) were confirmed by MLPA for the presence of the gene amplification. The
      overall concordance of detection of Her2 gene amplification by FISH and MLPA was
      98% (45/46). Furthermore, both the level of amplification and equivocal results
      correlated well between both methods. In conclusion, MLPA is a reliable and
      reproducible technique and can be used as an either alternative or additional
      test to determine HER2 status in breast carcinomas.

PMID- 16988471
TI  - KRAS, p53 and BRAF gene mutations and aneuploidy in sporadic colorectal cancer
      progression.
AB  - BACKGROUND: The origin and mechanisms of chromosomal instability are still widely
      unknown. We previously investigated a limited number of human sporadic colorectal
      cancers (CRCs) and observed a statistically different occurrence of KRAS and p53
      mutations among predetermined subgroups of tumors with different degrees of DNA
      aneuploidy. The aim of the present study was to further verify these observations
      by including BRAF gene analysis and by investigating a larger series of cases
      subdivided into Dukes' stages A to D to reconstruct some form of chronological
      modulation for events during CRC progression. METHODS: KRAS, p53, BRAF mutations
      and flow cytometric DNA Index were evaluated by established techniques in a
      series of 135 human sporadic CRCs. RESULTS: p53, KRAS and BRAF mutations were
      found in 39%, 34%, and 4% of tumors, respectively. The frequency of p53 mutations
      increased from 15% for stage A to 48% for stage D and was highest in near-diploid
      (DI < 1.4 and DI does not equal 1) and high-aneuploid (DI > 1.6) tumors. A
      similar correlation between gene mutations and DI values was observed for KRAS.
      The simultaneous presence of KRAS and p53 mutations was observed in only 11% of
      cases. Moreover, the co-occurrence of p53 and KRAS mutations was only observed in
      near-diploid and high-aneuploid tumors. CONCLUSION: Our findings suggest that
      KRAS and p53 gene mutations, which are rarely simultaneous and are associated
      with specific DI aneuploid values, do not represent a synergistic evolutionary
      pathway but may influence mechanisms of chromosomal instability.

PMID- 16988472
TI  - Cytokeratin profiles identify diagnostic signatures in colorectal cancer using
      multiplex analysis of tissue microarrays.
AB  - BACKGROUND AND AIMS: Recent cDNA expression profiling analyses indicate that
      within specific organ cancers Cytokeratins (CKs) dysregulation may identify
      subgroups with distinct biological phenotypes. Our objectives in this study were
      (1) to test whether cytokeratins were also distinct on the protein level, (2) to
      evaluate these biomarkers in a series of well-characterised CRCs, (3) to apply
      hierarchical cluster analysis to immunohistochemical data. METHODS: Tissue
      microarrays (TMA) comprising 468 CRC specimens from 203 patients were constructed
      to evaluate CK5, CK7, CK8, CK13, CK14, CK16, CK17, CK18, CK19 and CK20. In total,
      2919 samples were analyzed. RESULTS: Unsupervised hierarchical clustering
      discovered subgroups represented by reduced CK8 and CK20 expression, that
      differed by a shorter patients survival. The evaluation of the specific
      biomarkers by Kaplan-Meier analysis showed that reduced CK8 expression (p<0.01)
      was significantly associated with shorter patients' survival, but was not an
      independent factor correlated with tumour stage (pT), grading (G) and nodal stage
      (pN). CONCLUSIONS: Reduced coexpression of CK8 and CK20 may indicate an
      epithelial-mesenchymal transition (EMT) representing an important step in the
      development of more aggressive CRCs. In addition, multiplex analysis of TMAs
      together with immunohistochemistry (IHC) supplemented by hierarchical clustering
      are a useful, promising and very powerful tool for the identification of tumour
      subgroups with diagnostic and prognostic signatures.

PMID- 16988473
TI  - Hepatitis C virus core protein transforms murine fibroblasts by promoting genomic
      instability.
AB  - The oncogenic potential of hepatitis C virus (HCV) core protein has been
      demonstrated, but the precise mechanism of cell transformation triggered by HCV
      core is still unclear. This study shows that constitutive expression of HCV core
      protein (core) in NIH 3T3 murine fibroblasts triggers malignant transformation.
      At the preneoplastic stage, clones that expressed HCV core constitutively
      demonstrated genomic instability seen as disruption of the mitotic spindle cell
      checkpoint leading to increased ploidy. Transformation was completed by the loss
      of DNA and resistance to apoptosis induced by serum starvation. Simultaneously,
      cells acquired a capacity for anchorage independent growth and absence of contact
      inhibition. Inoculation of these transformed cells into severe combined immune
      deficiency (SCID) mice led to formation of solid core-expressing tumors.
      Transformation and tumorigenicity of core-expressing cell lines coincided with a
      5- to 10-fold repression of endogenous p53 transactivation. Thus, long-term HCV
      core expression alone is sufficient for complete transformation of immortal
      fibroblasts that can then induce tumors in a susceptible host. This data suggests
      that malignant transformation by HCV core may occur through primary stress,
      induction of genomic instability, and further HCV core-induced rescue of
      surviving mutated cells.

PMID- 16988474
TI  - Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease
      patients.
AB  - Treatment of Alzheimer's disease (AD) is difficult due to ignorance of its
      pathogenesis. AD patients have defects in phagocytosis of amyloid-beta (1-42)
      (Abeta) in vitro by the innate immune cells, monocyte/macrophages and in
      clearance of Abeta plaques [5]. The natural product curcuminoids enhanced brain
      clearance of Abeta in animal models. We, therefore, treated macrophages of six AD
      patients and 3 controls by curcuminoids in vitro and measured Abeta uptake using
      fluorescence and confocal microscopy. At baseline, the intensity of Abeta uptake
      by AD macrophages was significantly lower in comparison to control macrophages
      and involved surface binding but no intracellular uptake. After treatment of
      macrophages with curcuminoids, Abeta uptake by macrophages of three of the six AD
      patients was significantly (P<0.001 to 0.081) increased. Confocal microscopy of
      AD macrophages responsive to curcuminoids showed surface binding in untreated
      macrophages but co-localization with phalloidin in an intracellular compartment
      after treatment. Immunomodulation of the innate immune system by curcuminoids
      might be a safe approach to immune clearance of amyloidosis in AD brain.

PMID- 16988475
TI  - Neurine, an acetylcholine autolysis product, elevates secreted amyloid-beta
      protein precursor and amyloid-beta peptide levels, and lowers neuronal cell
      viability in culture: a role in Alzheimer's disease?
AB  - Classical hallmarks of Alzheimer's disease (AD) are a synaptic loss, cholinergic
      neuron death, and abnormal protein deposition, particularly of toxic amyloid-beta
      peptide (Abeta) that is derived from amyloid-beta protein precursor (AbetaPP) by
      the action of beta- and gamma-secretases. The trigger(s) initiating the
      biochemical cascades that underpin these hallmarks have yet to be fully
      elucidated. The typical forebrain cholinergic cell demise associated with AD
      brain results in a loss of presynaptic cholinergic markers and acetylcholine
      (ACh). Neurine (vinyl-trimethyl-ammonium hydroxide) is a breakdown product of
      ACh, consequent to autolysis and is an organic poison found in cadavre brain. The
      time- and concentration-dependent actions of neurine were assessed in human
      neuroblastoma (NB, SK-N-SH) cells in culture by quantifying cell viability by
      lactate dehydrogenase (LDH) and MTS assay, and AbetaPP and Abeta levels by
      Western blot and ELISA. NB cells displayed evidence of toxicity to neurine at >
      or = 3 mg/ml, as demonstrated by elevated LDH levels in the culture media and a
      reduced cell viability shown by the MTS assay. Using subtoxic concentrations of
      neurine, elevations in AbetaPP and Abeta1-40 peptide levels were detected in
      conditioned media samples.

PMID- 16988476
TI  - Non-invasive therapy to reduce the body burden of aluminium in Alzheimer's
      disease.
AB  - There are unexplained links between human exposure to aluminium and the
      incidence, progression and aetiology of Alzheimer's disease. The null hypothesis
      which underlies any link is that there would be no Alzheimer's disease in the
      effective absence of a body burden of aluminium. To test this the latter would
      have to be reduced to and retained at a level that was commensurate with an
      Alzheimer's disease-free population. In the absence of recent human interference
      in the biogeochemical cycle of aluminium the reaction of silicic acid with
      aluminium has acted as a geochemical control of the biological availability of
      aluminium. This same mechanism might now be applied to both the removal of
      aluminium from the body and the reduced entry of aluminium into the body while
      ensuring that essential metals, such as iron, are unaffected. Based upon the
      premise that urinary aluminium is the best non-invasive estimate of body burden
      of aluminium patients with Alzheimer's disease were asked to drink 1.5 L of a
      silicic acid-rich mineral water each day for five days and, by comparison of
      their urinary excretion of aluminium pre-and post this simple procedure, the
      influence upon their body burden of aluminium was determined. Drinking the
      mineral water increased significantly (P<0.001) their urinary excretion of
      silicic acid (34.3 +/- 15.2 to 55.7 +/- 14.2 micromol/mmol creatinine) and
      concomitantly reduced significantly P=0.037) their urinary excretion of aluminium
      (86.0 +/- 24.3 to 62.2 +/- 23.2 nmol/mmol creatinine). The latter was achieved
      without any significant (P>0.05) influence upon the urinary excretion of iron
      (20.7 +/- 9.5 to 21.7 +/- 13.8 nmol/mmol creatinine). The reduction in urinary
      aluminium supported the future longer-term use of silicic acid as non-invasive
      therapy for reducing the body burden of aluminium in Alzheimer's disease.

PMID- 16988477
TI  - Supplementation of the diet with silicic acid to reduce body burden of aluminum:
      a miracle cure or useless treatment for Alzheimer's disease?

PMID- 16988479
TI  - Aluminum and Alzheimer's disease: a Vexata Questio between uncertain data and a
      lot of imagination.

PMID- 16988480
TI  - The silicon link between aluminium and Alzheimer's disease.

PMID- 16988481
TI  - Kinetics of human serum butyrylcholinesterase and its inhibition by a novel
      experimental Alzheimer therapeutic, bisnorcymserine.
AB  - An explosion in the incidence of neurodegenerative diseases, particularly
      Alzheimer's disease (AD), is predicted in coming decades. Hence, the need to
      devise and assess new treatment strategies has never been more acute. AD,
      although an irreversible and progressive disorder, is currently treated with
      palliative, symptomatic therapy: primarily with acetylcholinesterase (AChE)
      inhibitors to amplify remaining cholinergic activity. New agents that,
      additionally, affect disease progression are sorely needed. Inhibition of brain
      butyrylcholinesterase (BuChE) represents a new drug target for AD treatment.
      Therefore, hand-in-hand with the development of selective ligands to inhibit
      BuChE in brain, it is fundamental to optimize assay conditions for kinetic
      studies of human BuChE. Kinetic analysis of serum BuChE, which is structurally
      similar to brain enzyme, was performed at dual substrate (butyrylthiocholine
      iodide) concentration ranges: 3-80 microM (low) and 25-800 microM (optimal) by
      use of the Ellman technique. Interaction of BuChE with a novel experimental AD
      therapeutic, bisnorcymserine (BNC; 0.06-2.0 nM) was also studied ex vivo. The
      IC_{50} and other key kinetic constants were determined for human serum BuChE
      inhibition by BNC, which proved to be a highly potent inhibitor in comparison to
      its structural analogue, cymserine. BNC may, additionally, lower the amyloid
      plaque-associated protein, amyloid-beta peptide. In synopsis, the
      characterization of the kinetic parameters of BuChE and BNC, described herein, is
      both aiding in the design of novel agents and optimizing their translation toward
      clinical use.

PMID- 16988482
TI  - The use of laboratory tests in patients with mild cognitive impairment.
AB  - Cognitive decline in elderly people can be caused by a specific and treatable
      metabolic disorder, and the use of laboratory tests is recommended as part of the
      diagnostic workup of patients with dementia. Patients with mild cognitive
      impairment (MCI) are commonly investigated by a similar laboratory diagnostic
      workup, however it is not known whether this clinical practice is justified. In
      the present study, we compared the frequencies of laboratory abnormalities, and
      laboratory abnormalities relevant for cognitive impairment, in consecutive
      patients with MCI or dementia (all types) observed in a memory clinic setting. As
      much as 55.1% of patients with MCI and 60.0% of patients with dementia had at
      least one abnormal laboratory value (a non-significant difference). The most
      frequent abnormal analysis was the serum cholesterol, that was high in 28.8% of
      patients with MCI and in 20.4% of patients with dementia. It was possible to
      detect, both in patients with MCI (1.5% and in patients with dementia (3.5%, a
      non-significant difference), abnormal metabolic values, indicating poorly
      controlled diabetes, renal failure, hyponatremia, folate or vitamin B12
      deficiency and hyperthyroidism, which correction led to clinical improvement. The
      majority (62.5% of these alterations were previously unknown. These findings give
      support to the use of the laboratory diagnostic workup of dementia in patients
      with mild cognitive impairment.

PMID- 16988483
TI  - Mitochondrial dysfunction, oxidative stress and neurodegeneration.
AB  - Mitochondria play a critical role in several metabolic processes and apoptotic
      pathways, regulating life cycle from the cradle to the grave. Despite the
      evidence of morphological, biochemical and molecular abnormalities in
      mitochondria in various tissues of patients with neurodegenerative disorders, the
      question "is mitochondrial dysfunction a necessary step in neurodegeneration?" is
      still unanswered. Moreover, a growing body of evidence seems to indicate that
      oxidative stress, which is increased in damaged mitochondria, is an earlier event
      associated with neurodegeneration. Here we examine the current evidences in this
      field, which indicate a key role of mitochondria and oxidative stress in
      contributing to the neurodegenerative processes.

PMID- 16988484
TI  - Neuroinhibitory molecules in Alzheimer's disease.
AB  - Aberrant neurite growth is one of the neuropathological signatures of the
      Alzheimer's disease brain, both around amyloid plaques and in the cortical
      neuropil. Disruption of neuroinhibitory or repulsive growth and guidance signals,
      as well as of neurotrophic or permissive signals, may contribute to this
      dystrophic growth. Hence, therapeutic efforts directed exclusively at restoring
      neurotrophic activity are unlikely to meet with success. The molecular species
      responsible for neuroinhibitory effects in the Alzheimer's disease brain are
      beginning to be elucidated.

PMID- 16988485
TI  - From tau to toxicity: emerging roles of NMDA receptor in Alzheimer's disease.
AB  - Glutamate toxicity through NMDA receptor channels has long been central to the
      understanding of acute neuronal injury. Recent studies implicate similar events
      in chronic neurodegenerative diseases. Here, we analyze some of the most
      intriguing evidence for NMDA receptor-mediated cellular dysfunction and propose a
      mechanism by which hyperactive NMDA receptors might lead to neurofibrillary
      degeneration in Alzheimer's disease.

PMID- 16988486
TI  - Therapeutic rescue of neurodegeneration in experimental type 3 diabetes:
      relevance to Alzheimer's disease.
AB  - Alzheimer's disease (AD) is associated with major impairments in insulin and
      insulin-like growth factor (IGF) gene expression and signaling in the brain.
      These abnormalities increase with severity of dementia, and are associated with
      deficiencies in energy metabolism and acetylcholine homeostasis. The co-existence
      of brain insulin/IGF deficiency and resistance suggests that AD may represent a
      brain-specific form of diabetes, i.e. Type 3 diabetes. This hypothesis is
      supported by the findings in an experimental animal model in which intracerebral
      (ic) Streptozotocin (STZ) was used to deplete brain and not pancreatic insulin.
      The ic-STZ treatment produced brain-specific insulin depletion and insulin
      resistance are associated with progressive neurodegeneration that shares many
      features in common with AD. We now demonstrate that early treatment with
      peroxisome-proliferator activated receptor agonists can effectively prevent ic
      STZ-induced neurodegeneration and its associated deficits in learning and memory.
      These effects were mediated by increased binding to insulin receptors, reduced
      levels of oxidative stress and tau phosphorylation, and increased choline
      acetyltransferase expression in the brain, suggesting that insulin sensitizer
      agents may have therapeutic efficacy in early AD.

PMID- 16988487
TI  - Angiogenic proteins are expressed by brain blood vessels in Alzheimer's disease.
AB  - Data are emerging to support the idea that mediators of angiogenesis are found in
      the Alzheimer's disease (AD) brain. The objective of this study is to compare the
      expression of the angiogenic mediators vascular endothelial growth factor (VEGF),
      angiopoietin, and matrix metalloproteinases (MMPs) in the microcirculation of AD
      patients and age-matched controls. Our results indicate that angiopoietin-2 and
      VEGF are expressed by AD- but not control-derived microvessels. AD-derived
      microvessels also release higher levels of MMP-2 and MMP-9 compared to controls.
      The data show that despite high levels of MMP-9, assessed by western blot, MMP-9
      activity is not detectable in AD microvessels. In this regard we find high levels
      of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in AD, but not
      control vessels. Furthermore, we explore the ability of thrombin, previously
      shown to be present in AD microvessels, to affect TIMP expression in cultured
      brain endothelial cells and find that thrombin causes up regulation of TIMP-1.
      These data show that angiogenic changes occur in the microcirculation of the AD
      brain and suggest that if these changes are contributory to disease pathogenesis,
      targeting the abnormal brain endothelial cell would provide a novel therapeutic
      approach for the treatment of this disease.

PMID- 16988489
TI  - Alzheimer research forum live discussion: not dead yet: estrogen deserves another
      chance.

PMID- 16988491
TI  - Changes of fructose concentrations in seminal plasma and glucose and testosterone
      concentrations in blood plasma in rams over the course of a year.
AB  - The present study was performed to examine seasonal changes in the fructose
      concentrations of seminal plasma and glucose and testosterone concentrations of
      blood plasma over the course of a year (from November 2004 to November 2005)
      using 5 Suffolk rams. Osmolality of the seminal plasma was also measured. The
      fructose concentrations in the seminal plasma increased as the breeding season
      approached, with the maximum in October (179.8 mg/dl) and the minimum in May (6.9
      mg/dl), although there were no significant differences during the year.
      Osmolality of the seminal plasma in February (304 mOsm) was significantly
      (P<0.05) lower than in January (325 mOsm), July (327 mOsm), and August (325
      mOsm). It was also significantly (P<0.05) lower in November (308 mOsm) than in
      January and August. The blood plasma glucose concentration in October (79.3
      mg/dl) was significantly (P<0.05) higher than in January and February (43.2 and
      43.7 mg/dl, respectively). The blood plasma testosterone (T) concentrations were
      significantly (P<0.05) higher in September (8.5 ng/ml) and October (10.2 ng/ml)
      than in other months. The fructose concentrations in the seminal plasma appeared
      to be related to the glucose and T concentrations in the blood plasma. These
      results show that fructose concentrations in the seminal plasma and blood plasma
      glucose and T concentrations tended to increase during the breeding season, with
      the highest concentrations in October.

PMID- 16988490
TI  - Identification of Jmjd1a as a STAT3 downstream gene in mES cells.
AB  - Mouse embryonic stem (mES) cells can be maintained in undifferentiated state in
      the presence of a cytokine, leukemia inhibitory factor (LIF). Many investigators
      found that STAT3 activation is important for the maintenance of pluripotency by
      LIF. However, the downstream pathways of STAT3 activation are still unknown. To
      look for STAT3-downstream target genes, we performed DD-RT PCR in the presence or
      absence of LIF. Through further confirmation, we finally selected 8 genes whose
      expressions were significantly dependent upon the presence of LIF. Among them,
      Jmjd1a was down-regulated after LIF withdrawal, and it was selected for further
      investigation. Its expression started to decrease 1 day after the removal of LIF,
      and disappeared on day 3. It was also shown that STAT3 could bind to the promoter
      region of Jmjd1a gene. These data demonstrate that Jmjd1a might be a critical
      signaling molecule underlying the maintenance of pluripotency in mES cells.

PMID- 16988492
TI  - Plasma cortisol and progesterone responses to low doses of adrenocorticotropic
      hormone in ovariectmized lactating cows.
AB  - The objective of this study was to describe the responses of the plasma
      progesterone and cortisol concentrations in ovariectomized lactating cows to low
      doses of adrenocorticotropic hormone (ACTH). The estrous cycles in 3 lactating
      cows were synchronized, and the cows were ovariectomized in the luteal phase.
      ACTH challenge tests were conducted at doses of 3, 6, 12 and 25 IU. Blood samples
      were collected at 30 min intervals, and the plasma progesterone and cortisol
      concentrations were analyzed by EIA. A concomitant rise in plasma progesterone
      and plasma cortisol was observed in cows treated with 12 IU or higher doses of
      ACTH. Significant increments in the plasma cortisol concentrations were observed
      at all doses of ACTH. The means (+/- SE) of the peak plasma progesterone
      concentrations after the 3, 6, 12 and 25 IU ACTH challenge tests were 0.6 +/-
      0.1, 1.3 +/- 0.4, 1.5 +/- 0.3 and 2.4 +/- 0.3 ng/ml, respectively. The means of
      the peak plasma cortisol concentrations in the 3 cows after the ACTH challenge
      were 14.0 +/- 1.5, 17.0 +/- 2.5, 23.3 +/- 3.0, and 33.3 +/- 7.0 ng/ml,
      respectively. The effects of the doses, time after treatment, and their
      interaction on the plasma progesterone concentrations after the ACTH challenge
      were significant (P<0.01). Likewise, the effects of the doses, time after
      treatment, and their interaction on the plasma cortisol concentrations after the
      ACTH challenge were significant (P<0.01). The mean AUC values for the plasma
      progesterone and cortisol concentrations after the ACTH treatments were also
      significantly affected by the dose of ACTH (P<0.01 and P<0.05, respectively). A
      significantly positive correlation was obtained between the peak plasma
      progesterone and cortisol concentrations after different doses of ACTH (r=0.7,
      P<0.05). The results suggest that lactating dairy cows are capable of secreting a
      significant amount of adrenal progesterone, reaching up to the minimal
      concentration necessary to cause suppression of estrus in response to 12 IU ACTH
      (P<0.01). The concomitant plasma cortisol concentration was 23.3 ng/ml.

PMID- 16988493
TI  - Radiation-induced brain cell death can be observed in living medaka embryos.
AB  - Medaka (Oryzias latipes) embryos at 25-26 and 28-30 stages were irradiated with a
      single acute dose of 10 Gy of X-ray, which is lower than the LD(50 )of the
      embryos. The effects on developing brains were examined under a stereomicroscope
      in living embryos until hatching. All the irradiated embryos survived; however,
      from 6 to 35 h after X-ray irradiation, massive clusters of optically opaque and
      round cells were observed either in the entire brain region (when irradiated at
      25-26 stages) or mainly in the optic tectum (when irradiated at 28-30 stages).
      Histological examination and TUNEL showed that these cells are clusters of dead
      cells. These dead cell clusters disappeared thereafter, and the irradiated
      embryos continued to develop apparently normally. The grown irradiated embryos,
      however, had smaller brains and eyes than the nonirradiated control embryos. At
      hatching, the irradiated embryos exhibited histological abnormalities in the
      brain, particularly in the torus longitudinalis, and in the retina, although most
      of them hatched normally and survived. The results indicate that brain cell death
      and a reduced brain size can be observed in living irradiated embryos, and
      suggest that the medaka embryo is useful for screening the developmental
      neurotoxicity effects of various hazardous factors.

PMID- 16988494
TI  - Adaptive response of blood lymphocytes of inhabitants residing in high background
      radiation areas of ramsar- micronuclei, apoptosis and comet assays.
AB  - The hot springs in certain areas of Ramsar contain (226)Ra and (222)Rn. The
      effects of natural radiation on the inhabitants of these areas and the
      inhabitant's radiosensitivity or adaptive responses were studied. One group of
      volunteers from areas with high natural background radiation and another group
      from areas with normal background radiation were chosen as the case and control
      group respectively. The frequency of micronuclei, apoptosis, and DNA damage in
      peripheral blood mononuclear cells were measured following gamma irradiation (4
      Gy). The incidence of micronuclei in the case group was significantly lower than
      that in the control group while their frequency of apoptosis was higher (P <
      0.05). However, the rates of induced DNA damage and repair were significantly
      higher in the case group (P < 0.05). Smaller number of micronuclei and higher
      levels of apoptosis in the case group could be the result of higher resistance to
      radiation stress and a more rigorous checkpoint at cell division. However,
      regarding the alkaline labile sites, the individuals in the case group are more
      sensitive and susceptible to DNA damage. The results of micronuclei, apoptosis
      and repair studies suggest that an adaptive response might be induced in people
      residing in areas with high background radiation.

PMID- 16988495
TI  - Increased levels of soluble TNF-alpha receptors and cellular adhesion molecules
      in patients undergoing bioincompatible hemodialysis.
AB  - BACKGROUND: The study aimed to differentiate the effects of hemodialysis (HD) and
      chronic renal failure (CRF) on the levels of circulating tumor necrosis factor
      alpha (TNF-alpha) and TNF-alpha receptors p55 and p75, soluble vascular cell
      adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1),
      soluble endothelial-leukocyte adhesion molecule-1 (sE-selectin) and sP-selectin
      in 18 patients on regular HD treatment with cuprophane membrane in relation to 15
      non-dialyzed CRF patients and 15 healthy controls. METHODS: The serum
      concentrations were determined with standard ELISA assays. RESULTS: Blood serum
      p75 and p55 were approximately tenfold increased in CRF (36.7 +/- 6.2 and 27.1 +/
      5.6 ng/ml) and HD patients (45.6 +/- 18.4 and 28.7 +/- 5.9 ng/ml) before the HD
      session (HD 0), during (HD 20) the session (45.7 +/- 18.4 and 28.5 +/- 7.3 ng/ml)
      and after (HD 240) the HD session (52.1 +/- 17.4 and 30.9 +/- 8.2 ng/ml) in
      comparison to control values (5.6 +/- 1.3 and 2.4 +/- 0.8 ng/ml, respectively) (p
      < 0.01). The highest increment of p75 at the end of HD session (HD 240) was also
      significantly higher than at preceding time points (HD 0 and 20) (p < 0.05).
      However, the remaining study parameters did not change during an HD session.
      Also, there were no relevant changes in TNF-alpha levels if (HD 0) 22.7 +/- 21.5
      ng/ml and (HD 240) 21.1 +/- 18.9 ng/ml were compared. Chronic HD status was
      related to the increase of sVCAM-1 and sICAM-1 levels. Prior to HD, T0 sVCAM-1
      and sICAM-1 concentrations were 2,180.4 +/- 761.8 and 567.3 +/- 218.8 ng/ml,
      during HD (T20): 2,172.7 +/- 759.2 and 602.3 +/- 379.9 ng/ml, and after HD
      (T240): 2,401.6 +/- 756.4 and 648.3 +/- 183.5 ng/ml, respectively (p < 0.05 vs.
      controls and CRF patients). sVCAM-1 and sICAM-1 serum levels (1,262.2 +/- 472.9
      and 165.6 +/- 50.4 ng/ml) were similar in CRF patients and healthy controls
      (854.4 +/- 241.5 and 217.6 +/- 74.2 ng/ml, respectively). Even though serum sE-
      and sP-selectin in CRF patients did not differ from the control (39.8 +/- 21.3
      vs. 42.1 +/- 18.9 ng/ml and 187.9 +/- 66.9 vs. 198.8 +/- 62.2 ng/ml,
      respectively), their levels were increased in HD patients up to 111.9 +/- 54.6
      and 453.2 +/- 231.1 ng/ml in patients prior to HD, 118.7 +/- 66.2 and 350.8 +/-
      114.8 ng/ml during the HD session and then 132.3 +/- 61.1 and 368.3 +/- 126.6
      ng/ml, respectively, after its completion (p < 0.05 in comparison with CRF
      patients and controls). CONCLUSIONS: The increased circulating TNF-alpha
      receptors appear more associated with the uremic milieu than HD-related systemic
      inflammation, whereas increased soluble cellular adhesion molecules in patients
      undergoing bioincompatible HD may be related to the enhanced systemic
      inflammation specifically due to maintenance HD.

PMID- 16988496
TI  - B-vitamin status and concentrations of homocysteine in Austrian omnivores,
      vegetarians and vegans.
AB  - BACKGROUND: A vegetarian diet is considered to promote health and longevity and
      reduce the risk of cardiovascular diseases and cancer. However, a vegetarian diet
      may be deficient in some nutrients. Exclusion of animal products in vegetarian
      diets may affect the status of certain B-vitamins, and further cause the rise of
      plasma homocysteine concentration. OBJECTIVE: The nutritional status of various B
      vitamins (B(1), B(2), B(6), B(12), folic acid) and the concentration of
      homocysteine in blood plasma of omnivores (n = 40), vegetarians (n = 36) and
      vegans (n = 42) in Austria was evaluated. METHODS: The evaluation was done using
      the functional parameters erythrocyte transketolase (ETK), glutathione reductase
      (EGR) and glutamic oxaloacetic transaminase (EGOT) activation coefficients.
      Enzyme activity was measured photometrically. The quantity of vitamins B(1), B(2)
      and B(6) in urine and the concentrations of vitamin B(6) and homocysteine in
      plasma were determined by HPLC methods with fluorescence detection. Plasma
      concentration of vitamin B(12) and folic acid were measured with
      radioimmunoassay. RESULTS: Most of the subjects showed a satisfying vitamin B(1)
      status. Vegans presented a significantly lower mean plasma vitamin B(12)
      concentration than omnivores and vegetarians and deficiency in 2.4% of the
      volunteers but the highest mean value of plasma folate among the investigated
      groups. A deficient status of folate was found in 18% of omnivores and in
      approximately 10% of vegans and vegetarians. The status of riboflavin is
      considered to be deficient in about 10% of omnivores and vegetarians and in over
      30% of vegans. According to the activation coefficient of GOT, approximately one
      third of all subjects showed vitamin B(6) deficiency. Elevated homocysteine
      concentration in plasma was observed in 66% of the vegans and about 45-50% of the
      omnivores and vegetarians. Vegan subjects had significantly higher mean plasma
      homocysteine levels than omnivores. CONCLUSION: Thiamin and folate need not be a
      problem in a well-planned vegan diet. Vitamins B(12) and B(2) may need attention
      in the strict vegan diet, especially regarding elevated homocysteine levels in
      plasma. Pyridoxine status appeared to be independent of the diet.

PMID- 16988498
TI  - Inner ear therapy for neural preservation.
AB  - A gradual loss of auditory neurons often occurs following sensorineural hearing
      loss. Since the cochlear implant must stimulate the remaining auditory neuron
      population, it would be beneficial to preserve as many auditory neurons as
      possible. Neurotrophic factors protect auditory neurons from degradation after
      sensorineural hearing loss in experimental animals, but have not yet been
      translated into the clinical setting. Current experimental and clinical
      techniques for drug delivery to the inner ear are examined in this review,
      covering the routes for drug delivery to the cochlea and the delivery systems
      used to introduce them. Duration of treatment, drug diffusion, effectiveness and
      safety are discussed with references to how they may be translated to the
      implementation of neurotrophic factor treatment for neural preservation.

PMID- 16988497
TI  - Diet and gene expression: delta-5 and delta-6 desaturases in healthy Chinese and
      European subjects.
AB  - AIM: To compare the composition of fatty acids (FAs) in diet, and the expression
      of delta-6 desaturase (D6D) and delta-5 desaturase (D5D) genes in peripheral
      blood mononuclear cells (PBMCs) between Chinese and Europeans. METHODS: Three-day
      dietary records from 20 subjects from Beijing, China (n = 10) and Kent, UK (n =
      10) were analysed. Expression of PBMC D6D and D5D genes of the subjects was
      determined using RT-PCR. RESULTS: The dietary intake of Chinese subjects
      contained less saturated fatty acids (SFAs) and monounsaturated fatty acids
      (MUFAs), but more essential fatty acids (EFAs) than that of Europeans. Levels of
      expression of PBMC D6D and D5D genes of Chinese subjects were significantly lower
      than those of Europeans. A significant positive correlation was found between
      dietary intake of total SFAs and total MUFAs and expression of PBMC D6D and D5D
      genes, but a significant negative correlation between dietary intake of linoleic
      acid (LA) and alpha-linolenic acid (LNA) and the expression of PBMC D6D and D5D
      genes. CONCLUSION: Intake of high SFAs and MUFAs appears to increase expression
      of PBMC D6D and D5D genes, whilst high EFAs intake appears to decrease expression
      of PBMC D6D and D5D genes. A follow-up study of the expression of D6D and D5D
      genes in Chinese who live in European countries with high SFA and MUFA diets
      would be of interest.

PMID- 16988499
TI  - Local perfusion of the tumor necrosis factor alpha blocker infliximab to the
      inner ear improves autoimmune neurosensory hearing loss.
AB  - OBJECTIVE: To evaluate the effect of transtympanic administration of tumor
      necrosis factor alpha (TNF-alpha) blockers to patients suffering from autoimmune
      inner ear disease (AIED). STUDY DESIGN: Nonrandomized, prospective pilot study.
      SETTING: Tertiary referral center. PATIENTS: 9 patients (4 men and 5 women; aged
      51.22 +/- 13.11 years) presenting with autoimmune sensorineural hearing loss who
      responded to oral steroid treatment. Two groups of patients were treated. Group A
      consisted of 5 patients with AIED who could not be tapered off steroids. Group B
      consisted of 4 patients who were treated with intratympanic anti-TNF-alpha
      antibody therapy alone after a relapse of hearing loss following discontinuation
      of steroids. INTERVENTION: A Silverstein MicroWick local delivery system was
      placed in the round window niche and the patients were treated for 4 weeks with a
      weekly infusion of infliximab, a monoclonal antibody against TNF-alpha. MAIN
      OUTCOME MEASURE(S): Evaluation of hearing thresholds at 250-8000 Hz was performed
      before and after implantation of the Silverstein MicroWick and local delivery of
      the TNF-alpha blocker. RESULTS: Local administration of the TNF-alpha blocker
      allowed methylprednisolone to be tapered off without loss of hearing function in
      4/5 steroid-dependent patients. Four additional patients were treated only with
      anti-TNF-alpha perfusion to the round window membrane without concomitant
      systemic administration of methylprednisolone. In 3 of these 4 patients, the pure
      tone average improved to 22.6 +/- 15.7 dB, resulting in hearing recovery
      comparable to treatment with systemic methylprednisolone. The 7 responding
      patients showed a significant reduction of recurrence of hearing loss to 0.028 +/
      0.072 episodes per month over the 4.3 +/- 2.4 months of the post-treatment
      period compared to 0.84 +/- 0.4 recurrences per week seen in the pretreatment
      period. CONCLUSIONS: The results of this pilot trial demonstrate that in patients
      with AIED, transtympanic delivery of the TNF-alpha blocker infliximab once weekly
      for 4 weeks allowed steroids to be tapered off, resulted in hearing improvement
      and reduced disease relapses. These preliminary efficacy and safety results
      appear encouraging enough to warrant further follow-up and studies for better
      determination of the potential clinical utility of local administration of
      infliximab for autoimmune hearing loss.

PMID- 16988500
TI  - Contralateral suppression of transient evoked otoacoustic emissions in children
      with auditory processing disorder.
AB  - This study concerns contralateral white noise suppression of transient evoked
      otoacoustic emissions (TEOAEs) in children with auditory processing disorder
      (APD). Fifty-one children between 7 and 11 years were assigned to 1 of 3
      experimental groups: those without auditory complaints (n = 15), those with APD
      who scored high on a standardized test (n = 20) and those with APD who scored
      lower on the same test (n = 16). For all groups TEOAE suppression was determined
      in both linear and nonlinear acquisition mode. The results provide evidence that
      abnormal TEOAE suppression was significantly more common in the APD groups than
      in the control group. Contralateral suppression of TEOAE is an additional tool
      for assessing the efferent pathway in children with APD.

PMID- 16988501
TI  - Characteristics of hearing loss in HDR (hypoparathyroidism, sensorineural
      deafness, renal dysplasia) syndrome.
AB  - Haploinsufficiency of the zinc finger transcription factor GATA3 causes the triad
      of hypoparathyroidism, deafness and renal dysplasia, known by its acronym HDR
      syndrome. The purpose of the current study was to describe in detail the auditory
      phenotype in human HDR patients and compare these to audiometrical and
      histological data previously described in a mouse model of this disease. Pure
      tone audiometry, speech audiometry, speech in noise, auditory brainstem responses
      and transiently evoked otoacoustic emissions were measured in 2 patients affected
      by HDR syndrome. Both patients were affected by a moderate-to-severe
      sensorineural hearing loss. Speech reception thresholds were shifted and speech
      recognition in noise was disturbed. No otoacoustic emissions could be generated
      in either patient. Auditory brainstem response interpeak intervals were normal.
      The human and murine audiological phenotypes seem to correspond well. Hearing
      loss in HDR syndrome is moderate to severe, seems to be slightly worse at the
      higher end of the frequency spectrum and may be progressive with age. The absence
      of otoacoustic emissions and the loss of frequency selectivity suggest an
      important role for outer hair cells in causing the hearing loss.

PMID- 16988502
TI  - Biomechanical modeling and design optimization of cartilage myringoplasty using
      finite element analysis.
AB  - The purpose of this study was to determine the acoustic transfer characteristics
      of cartilage for optimal cartilage myringoplasty. In order to do so, we developed
      a cartilage plate/tympanic membrane-coupled model using finite element analysis.
      Cartilage specimens of the tragus were obtained from fresh human cadavers, and
      the parameters of the tragus were determined by curve fitting and cross
      calibration. A cartilage plate was used to repair an eardrum perforation, and the
      new coupled tympanic membrane-cartilage complex was loaded into our 3-dimensional
      biomechanical model of the middle ear for analysis. Our results show that first
      the beta-damping value of the cartilage plate depends on frequency. The value of
      beta damping was close to 3 x 10(-4) s at lower frequencies and 5 x 10(-6) s at
      higher frequencies. Secondly, reducing cartilage thickness leads to an
      improvement of its acoustic transfer qualities. From an acoustics point of view,
      the 0.1- to 0.2-mm cartilage plate seems to be most preferable with regard to
      tympanic membrane vibration. Furthermore, thicknesses of 0.2 mm at lower
      frequencies and 0.1 mm at higher frequencies were regarded as good compromises
      between sufficient mechanical stability and low acoustic transfer loss.

PMID- 16988503
TI  - Influence of the progression of cryptococcal meningitis on brain penetration and
      efficacy of AmBisome in a murine model.
AB  - BACKGROUND: AmBisome is a small unilamellar vesicle containing amphotericin B.
      AmBisome is generally unable to pass through the blood-brain barrier, but the
      distribution of AmBisome in the brain is increased by inflammation, and in
      consequence, AmBisome exhibits activity against fungal meningitis. We
      investigated the influence of the progression of cryptococcal meningitis on the
      brain penetration and efficacy of AmBisome. METHOD: Mice were infected
      intracerebroventricularly with Cryptococcus neoformans 4 h or 5 days prior to a
      single dose treatment. RESULTS: The brain tissue level and efficacy of AmBisome
      when administered 5 days after infection were greater than 4 h after infection.
      An immunohistochemical study showed that AmBisome-derived amphotericin B was
      localized at the infected site in the subarachnoid space. When AmBisome was
      compared with Fungizone at the maximum tolerated dose, 10 mg/kg AmBisome
      exhibited greater efficacy than 1 mg/kg Fungizone in both regimens. CONCLUSION:
      The brain penetration of AmBisome was enhanced by the progression of cryptococcal
      meningitis and correlated with the in vivo activity.

PMID- 16988504
TI  - Is primary hyperaldosteronism a risk factor for aortic dissection?
AB  - Primary hyperaldosteronism is a rare (<1%) and underdiagnosed cause of secondary
      hypertension. We present a case of aortic dissection in a patient with primary
      hyperaldosteronism. To our knowledge, there are six other reported cases of
      aortic dissection in patients with primary hyperaldosteronism. Our case
      strengthens the hypothesis that primary hyperaldosteronism is a potential
      independent risk factor for aortic dissection.

PMID- 16988505
TI  - Association analysis of peroxisome proliferator-activated receptor gamma
      polymorphisms and late onset Alzheimer's disease in the Finnish population.
AB  - Alzheimer's disease (AD), especially late-onset AD (LOAD), is a complex disease.
      To date, the only established genetic risk factor for LOAD is apolipoprotein E
      (APOE) epsilon4, which explains partially the risk of the disease and modifies
      the age of onset. Peroxisome proliferator-activated receptor gamma (PPARgamma)
      regulates the transcription of BACE1 as well as inflammatory responses in the
      brain and atherosclerotic risk factors known to be involved also in AD. Based on
      these findings, the gene encoding PPARgamma can be viewed as an interesting
      candidate in AD. We examined the effect of the two previously reported variants
      of PPARgamma polymorphisms, the Pro12Ala and exon 6 C478T, on the risk of LOAD
      and age of onset in a population-based follow-up sample of aged subjects (125
      LOAD patients and 462 non-demented controls). The genetic risk of AD was not
      significantly associated with the studied polymorphisms, but the PPARgamma Ala12
      478T genotype carriers were significantly younger at the onset of dementia than
      the non-carriers (p = 0.026). These results suggest that the PPARgamma gene may
      modify the age of onset in LOAD.

PMID- 16988506
TI  - Validation of the seven-minute screen neurocognitive battery for the diagnosis of
      dementia in a Spanish population-based sample.
AB  - OBJECTIVE: To validate the Seven-Minute Screen Neurocognitive Battery (7MS) in an
      elderly population-based sample to identify dementia using a new scoring method.
      METHODS: Five hundred and twenty-seven home-dwelling elderly were assessed with a
      neurological and neuropsychological exam. The total score of the 7MS was the sum
      of z scores of its subtests. Dementia was diagnosed according to DSM-IV. The ROC
      curve and the diagnostic parameters of the 7MS were calculated. RESULTS: The 7MS
      could be fully applied in 416 cases (78.9%), and 48 were diagnosed as demented
      independently of the 7MS. The four 7MS subtests correctly classified 97.6% of
      cases by discriminant analysis; orientation and memory were the most
      discriminative. Factorial analysis showed a single dimension in the 7MS. The ROC
      curve area for diagnosis of dementia was 0.996 (95% CI 0.992-1), sensitivity
      100%, specificity 95.1%, and diagnostic accuracy 96.8%. All these parameters were
      higher than those of other cognitive screening tests. Dementia explained 54.9% of
      the variance of the 7MS, and age 3.1%; sex and education did not have a
      significant effect. CONCLUSIONS: The 7MS is a valid tool for the diagnosis of
      dementia, even when cognitive decline is mild, although it may not be appropriate
      for extensive epidemiological surveys.

PMID- 16988507
TI  - Low-dose oxaliplatin enhances the antitumor efficacy of paclitaxel in human
      gastric cancer cell lines.
AB  - BACKGROUND: The enhanced antitumor effect of paclitaxel when used with
      oxaliplatin in gastric cancer is reported, however the underlying biological
      mechanism is unknown. METHODS: We tested the cytotoxic activity, apoptosis, and
      mitotic catastrophe of paclitaxel and oxaliplatin in MKN-28 and MKN-45 gastric
      cancer cell lines. The modulation of survivin expression was determined by
      Western blotting. RESULTS: WST-1 assay indicated that paclitaxel plus oxaliplatin
      showed better cytotoxicity than paclitaxel alone, even when low concentrations of
      oxaliplatin were used. Flow cytometry analysis revealed significantly greater
      increases in apoptotic cells after treatment with paclitaxel followed by low-dose
      oxaliplatin (1 microM) than after any single-reagent regimen in the MKN-45 cell
      line. In MKN-28, a difference existed only between combination treatment and
      oxaliplatin treatment. Morphologic examination showed that the cells undergoing
      mitotic catastrophe were highest in the combination groups in the both cell
      lines. Downregulation of survivin expression was found by Western blotting with
      treatment by paclitaxel, oxaliplatin, or their combination. CONCLUSION: Our
      findings suggest that the mechanism of enhanced cytotoxicity might be through
      enhanced mitotic catastrophe and apoptosis, which is possibly due to chemotherapy
      induced downregulation of surviving. The combination of paclitaxel and low-dose
      oxaliplatin should be incorporated into the design of a clinical trial.

PMID- 16988508
TI  - Fatal liver failure in an adult patient with acute lymphoblastic leukemia
      following treatment with L-asparaginase.
AB  - L-Asparaginase is commonly used in combination chemotherapy of both pediatric and
      adult acute lymphoblastic leukemia. The majority of adverse effects are
      hypersensitivity reactions, but serious liver injury may also occur. It has been
      shown that treatment with L-asparaginase can be associated mainly with
      macrovesicular hepatic steatosis which may be accompanied by alterations in lipid
      metabolism. So far, the mechanism for liver injury associated with L-asparaginase
      is not known. We report here an adult patient who developed mixed liver injury
      and predominantly microvesicular hepatic steatosis while being treated with L
      asparaginase for acute lymphoblastic leukemia. The patient developed liver
      failure and died due to multiorgan failure. Both impaired liver mitochondrial
      function and alterations in very-low-density lipoprotein metabolism and secretion
      are discussed as two possible mechanisms explaining the findings observed in this
      patient.

PMID- 16988509
TI  - Mild cognitive impairment: what's in a name?
AB  - BACKGROUND: Nowadays the term mild cognitive impairment (MCI) is used to fill the
      gap between cognitive changes associated with normal ageing and those associated
      with dementia. Despite some agreement in general definitions, MCI is still a
      heterogeneous clinical syndrome for which no DSM-IV criteria have yet been
      established. Criteria by Petersen et al. are presently the most applied in
      clinical practice. Moreover, little attention has been paid to the specific
      relation between MCI and depression. OBJECTIVE: This review highlights some
      concerns about the concept of MCI and provides guidelines within the field of
      neuropsychology to solve them. In a second part, the paper focuses on the
      specific relationship between depression in the elderly and MCI. RESULTS: We
      hypothesize that certain test instruments can be used to operationalize the
      criteria proposed by Petersen et al. Moreover, we suggest that cued recall might
      be of help to differentiate between progressive and non-progressive MCI.
      Concerning the specific relation between depression and MCI, we assume that
      elderly depression with concomitant cognitive problems can be seen as an MCI.
      CONCLUSION: The proposed adjustments and additions (neuropsychological
      instruments and the incorporation of depressive symptoms) in the diagnostic
      flowchart of Petersen may serve as useful tools for clinicians when making a
      diagnosis of MCI.

PMID- 16988510
TI  - Durban 2000 to Toronto 2006: the evolving challenges in implementing AIDS
      treatment in Africa.

PMID- 16988511
TI  - Elimination of HIV-1 infection by treatment with a doxorubicin-conjugated anti
      envelope antibody.
AB  - OBJECTIVE: To test the efficacy of an immunoconjugate against HIV-1. DESIGN: : A
      murine monoclonal antibody against the envelope antigen of HIV (P4/D10) was
      conjugated with the conventional anticancer drug, doxorubicin, and tested against
      infectious virus and infected cells, both in vitro and in vivo. METHODS: P4/D10
      antibody was incubated with free virus (neutralization) or HIV-infected cells
      (inhibition) and the resulting infection was measured by a p24 capture enzyme
      linked immunosorbent assay. In an HIV-1/MuLV murine challenge model, the ability
      of the conjugate to inhibit infection in vivo was measured. RESULTS: Doxorubicin
      conjugated P4/D10 neutralized HIV-1IIIB and eliminated intercellular spread and
      HIV replication in infected Jurkat cells in vitro. The conjugate also protected
      mice from challenge with HIV-1IIIB/MuLV at an eightfold lower concentration than
      needed for free antibody, whereas no effects were observed for comparable doses
      of free drug or irrelevant conjugate controls. CONCLUSION: This indicates that
      doxorubicin is concentrated to HIV-infected cells by the P4/D10 antibody,
      significantly (P = 0.0001) contributing to HIV elimination. This concept could
      also be adapted to eradicate remaining antigen-expressing T cells in patients
      treated with antiretroviral therapy.

PMID- 16988512
TI  - An anti-HIV microbicide engineered in commensal bacteria: secretion of HIV-1
      fusion inhibitors by lactobacilli.
AB  - OBJECTIVES: To engineer Lactobacillus spp. to secrete HIV-1 fusion inhibitors
      with potent neutralizing activity against primary HIV-1 isolates. METHODS: HIV-1
      fusion inhibitors (FI-1, FI-2, and FI-3) were introduced into the previously
      developed shuttle vector pTSV2 and transformed in L. plantarum and L. gasseri.
      The signal peptide Usp45 from L. lactis was used to achieve high secretion
      efficiency of peptides into the bacterial supernatant. The antiviral activity of
      lactobacillus-derived HIV-1 fusion inhibitors was tested against a panel of
      primary HIV-1 isolates and a chimeric simian/HIV (SHIV-162P3) using the TZM
      infection assay. TZM-bl cells are engineered HeLa cells that express CD4, CCR5,
      and CXCR4 and contain integrated reporter genes for firefly luciferase and beta
      galactosidase under the control of an HIV-1 long terminal repeat. The amount of
      secreted fusion inhibitor FI-3 was determined by Western blot analysis and the
      antiviral specificity verified by antibody-mediated depletion of peptide FI-3 and
      HIV-1 infection with VSV-G envelope pseudotyped virions. RESULTS: Viral
      infectivity of primary HIV-1 isolates and SHIV-162P3 was neutralized by up to 98%
      and 72%, respectively, by 10% (v/v) lactobacillus supernatant containing fusion
      inhibitor FI-3. The antiviral activity of the lactobacillus-derived fusion
      inhibitor FI-3 was clearly shown to be attributable to the secreted fusion
      inhibitor peptide. CONCLUSION: The development of recombinant lactobacilli
      expressing HIV-1 fusion inhibitors with potent neutralizing activity represents
      an important step toward the development of a live microbial (topical)
      microbicide against HIV-1 transmission.

PMID- 16988513
TI  - Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term non
      progressors: prevalence and association with neutralizing activity.
AB  - OBJECTIVE: Previous studies have shown that broadly neutralizing antibodies (NAb)
      are more frequent in long-term non-progressors (LTNP) than in other HIV-1
      infected patients, but nothing is known about the envelope regions targeted by
      these broadly NAb. We investigated whether the breadth of neutralizing activity
      of sera was associated with the presence of specific antibodies (2F5- and/or 4E10
      like, b12-like or 2G12-like antibodies) directed against conserved epitopes known
      to be involved in broad neutralization. METHODS: We assessed the ability of sera
      from 67 LTNP of the French ANRS cohort (ANRS CO15) to neutralize four
      heterologous primary isolates of four various clades. Competitive and non
      competitive ELISA were developed for the specific comparison of levels of
      antibodies against these specific epitopes in neutralizing and non-neutralizing
      sera from LTNP. RESULTS: We found that higher 2G12-like antibody levels were
      significantly associated with the broadest neutralizing activity in sera from
      LTNP. Levels of 2G12-like antibodies were higher in the sera that neutralized the
      four isolates than in the others, with a median of 5.7 microg/ml [interquartile
      range (IQR), 2.7-9.3 microg/ml] versus 2.3 microg/ml (IQR, 1.1-3.9 microg/ml)
      (Mann-Whitney test, P = 0.03). Levels of antibodies against the other targeted
      envelope epitopes did not differ significantly between broadly and non-broadly
      neutralizing sera. CONCLUSION: These results suggest that the antigenicity of the
      "silent face" of gp120 that exposes the 2G12 epitope should be analysed in more
      detail, to find ways to induce broadly neutralizing antibodies.

PMID- 16988514
TI  - Reduced lopinavir exposure during pregnancy.
AB  - BACKGROUND: Optimal antiretroviral exposure during pregnancy is critical for
      prevention of mother-to-child HIV transmission and for maternal health. Pregnancy
      can alter antiretroviral pharmacokinetics. Our objective was to describe
      lopinavir/ritonavir (LPV/r) pharmacokinetics during pregnancy. METHODS: We
      performed intensive steady-state 12-h pharmacokinetic profiles of lopinavir and
      ritonavir (three capsules: LPV 400 mg/r 100 mg) at 30-36 weeks gestation and 6-12
      weeks postpartum. Maternal and umbilical cord blood samples were obtained at
      delivery. We measured LPV and ritonavir by reverse-phase high-performance liquid
      chromatography. Target LPV area under concentration versus time curve (AUC) was >
      or = 52 microg h/ml, the estimated 10th percentile LPV AUC in non-pregnant
      historical controls (mean AUC = 83 microg h/ml). RESULTS: Seventeen women
      completed antepartum evaluations; average gestational age was 35 weeks. Geometric
      mean antepartum LPV AUC was 44.4 microg h/ml [90% confidence interval (CI), 38.7
      50.9] and 12-h post-dose concentration (C12h) was 1.6 microg/ml (90% CI, 1.1
      2.5). Twelve women completed postpartum evaluations; geometric mean LPV AUC was
      65.2 microg h/ml (90% CI, 49.7-85.4) and C12h was 4.6 microg/ml (90% CI, 3.7
      5.7). The geometric mean ratio of antepartum/postpartum LPV AUC was 0.72 (90% CI,
      0.54-0.96). Fourteen of 17 (82%) pregnant and three of 12 (25%) postpartum women
      did not meet our target LPV AUC. The ratio of cord blood/maternal LPV
      concentration in ten paired detectable samples was 0.2 +/- 0.13. CONCLUSIONS:
      LPV/r exposure during late pregnancy was lower compared to postpartum and
      compared to non-pregnant historical controls. Small amounts of lopinavir cross
      the placenta. The pharmacokinetics, safety, and effectiveness of increased LPV/r
      dosing during the third trimester of pregnancy should be investigated.

PMID- 16988515
TI  - Comparison of the risks of atherosclerotic events versus death from other causes
      associated with antiretroviral use.
AB  - BACKGROUND: Studies considering the risk of atherosclerotic disease (AtD)
      associated with the use of HAART have reported inconsistent results. METHODS:
      Data on antiretroviral therapy (ART) use, risk factors for cardiovascular disease
      (CVD), AtD and death from other causes in 18 603 HIV-infected patients from two
      established cohorts were evaluated. The relative hazards of AtD and death from
      other causes were calculated using a proportional hazards competing risks
      framework. The impact of protease inhibitor (PI)-containing, non-nucleoside
      reverse transcriptase inhibitor (NNRTI)-containing or PI + NNRTI-containing
      regimens on these outcomes were compared to nucleoside reverse transcriptase
      inhibitor (NRTI)-only regimens or stopping therapy, adjusting for known CVD risk
      factors. RESULTS: In 77 480 person-years of follow-up (median duration 3.49
      years) there were 318 AtD events including 92 myocardial infarctions and 2044
      deaths. Older age, hypertension, diabetes mellitus, having smoked and HIV disease
      stage were significantly associated with increased risk of AtD. PI- and NNRTI
      containing regimens significantly reduced the joint risk of either AtD or death
      from other causes compared to NRTI-only or stopping therapy [hazard ratio (HR)
      for PI-containing ART, 0.76, 95% confidence interval (CI), 0.73-0.78, P< 0.001;
      NNRTI-containing ART, 0.69, 95% CI, 0.65-0.74; P< 0.001). PI-containing ART was
      associated with a borderline significant increased risk of myocardial infarction
      (cause-specific HR for PI-containing ART 1.19, 95% CI, 1.01-1.40, P = 0.04) but
      not with increased risk of AtD compared to NRTI-only regimens or stopping therapy
      (cause-specific HR for PI-containing ART, 1.03, 95% CI, 0.95-1.13, P = 0.44).
      CONCLUSIONS: Overall benefits of PI- and NNRTI-based ART in reducing mortality
      significantly outweigh any risks of AtD in the "short-term" follow-up of this
      study. Traditional cardiac risk factors play an important role in determining AtD
      risk status.

PMID- 16988517
TI  - In resource-limited settings good early outcomes can be achieved in children
      using adult fixed-dose combination antiretroviral therapy.
AB  - OBJECTIVES: To (a) determine early treatment outcomes and (b) assess safety in
      children treated with adult fixed-dose combination (FDC) antiretroviral tablets.
      SETTING: Sixteen Medecins Sans Frontieres (MSF) HIV programs in eight countries
      in resource-limited settings (RLS). METHODS: Analysis of routine program data
      gathered June 2001 to March 2005. RESULTS: A total of 1184 children [median age,
      7 years; inter-quartile range (IQR), 4.6-9.3] were treated with antiretroviral
      therapy (ART) of whom 616(52%) were male. At ART initiation, Centres for Disease
      Control stages N, A, B and C were 9, 14, 38 and 39%, respectively. Children were
      followed up for a median period of 6 months (IQR, 2-12 months). At 12 months the
      median CD4 percentage gain in children aged 18-59 months was 15% (IQR, 6-18%),
      and the percentage with CD4 gain < 15% was reduced from 85% at baseline to 11%.
      In those aged 60-156 months, median CD4 cell count gain was 275 cells/microl
      (IQR, 84-518 cells/microl), and the percentage with CD4 < 200 cells/mul reduced
      from 51% at baseline to 11%. Treatment outcomes included; 1012 (85%) alive and on
      ART, 36 (3%) deaths, 15 (1%) stopped ART, 89 (8%) lost to follow-up, and 31 (3%)
      with unknown outcomes. Overall probability of survival at 12 months was 0.87
      (0.84-0.89). Side effects caused a change to alternative antiretroviral drugs in
      26 (2%) but no deaths. CONCLUSIONS: Very satisfactory early outcomes can be
      achieved in children in RLS using generic adult FDC antiretroviral tablets. These
      findings strongly favour their use as an "interim solution" for scaling-up ART in
      children; however, more appropriate pediatric antiretroviral drugs remain
      urgently needed.

PMID- 16988516
TI  - Combination of tenofovir and lamivudine versus tenofovir after lamivudine failure
      for therapy of hepatitis B in HIV-coinfection.
AB  - OBJECTIVE: At present sequential monotherapy for chronic hepatitis B with
      hepatitis B virus (HBV)-polymerase inhibitors is clinical practice. It is unknown
      to date whether combination therapy with lamivudine plus tenofovir could be
      superior to sequential therapy with tenofovir after the occurrence of lamivudine
      resistance. METHODS: We conducted a multicenter, 1: 2 matched pair analysis
      comparing patients with HBV/HIV-coinfection starting an antiretroviral regimen
      including tenofovir plus lamivudine with patients who had highly replicative,
      lamivudine resistant HBe-antigen positive chronic hepatitis B and started with
      tenofovir as the only active HBV polymerase inhibitor subsequent to lamivudine.
      RESULTS: At baseline patients on tenofovir plus lamivudine (n = 25) had a median
      HBV DNA of 5.9 x 10(7) copies/ml compared to 1.37 x 10(8) copies/ml in the
      tenofovir arm (n = 50; P = 0.32). A sustained undetectable HBV DNA < 1000
      copies/ml was achieved in 19/25 (76%) patients on tenofovir plus lamivudine and
      in 42/50 (84%) on tenofovir (P = 0.53). A loss of HBe-antigen was observed in
      9/25 (36%) patients on tenofovir plus lamivudine and in 12/50 (24%) patients on
      tenofovir (P = 0.29). HBs-antigen loss was found in 1/25 (4%) and 3/50 (6%)
      patients. CONCLUSIONS: In this cohort of HBV/HIV-coinfected individuals, full HBV
      DNA suppression was achieved in the majority of patients independent of treatment
      allocation. Loss of HBe- and HBs-antigen was not different between the two study
      arms. Over a median treatment period of 116 weeks tenofovir was as effective as
      tenofovir plus lamivudine. Longer treatment periods may be needed to evaluate
      potential benefits of first-line combination therapy for chronic hepatitis B.

PMID- 16988518
TI  - Peer referral for HIV case-finding among men who have sex with men.
AB  - OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of a health
      department-based peer referral program for identifying previously undiagnosed
      cases of HIV among men who have sex with men (MSM). DESIGN AND METHODS: Between
      2002 and 2005, 283 MSM peer recruiters were enrolled in a public health program
      in King County, Washington, USA. Peer recruiters were enrolled from a sexually
      transmitted disease (STD) clinic, an HIV clinic, via media advertisements and
      through collaboration with community-based organizations (CBO). The peer
      recruiters underwent a brief training and were then paid US$ 20 for each peer
      they referred to be tested for HIV, STD and viral hepatitis. Peers were paid US$
      20 for being tested. The main outcome measure was the number of new cases of HIV
      identified and cost per case of HIV identified. RESULTS: Recruiters referred 498
      peers for HIV, STD and hepatitis testing. Among 438 peers not previously
      diagnosed with HIV, 22 (5%) were HIV positive, of whom 18 received their HIV test
      results. Other infections were variably prevalent among tested peers: gonorrhea
      [23/307 (8%)], chlamydia [6/285 (2%)], syphilis [1/445 (0.2%)], hepatitis C
      [61/198 (31%)], surface antigen positive hepatitis B [8/314 (3%)]. Excluding the
      costs of testing for viral hepatitis and STDs other than HIV, the cost per new
      HIV case identified was US$ 4929. During the same period, the cost per new case
      of HIV detected through bathhouse-based HIV testing and through the county's
      largest CBO-based HIV testing program were US$ 8250 and US$ 11 481, respectively.
      CONCLUSIONS: Peer referral is an effective means of identifying new cases of HIV
      among MSM.

PMID- 16988519
TI  - HIV-1 acquisition and disease progression are associated with decreased high-risk
      sexual behaviour among Kenyan female sex workers.
AB  - BACKGROUND: Changes in sexual risk behaviour may occur following HIV-1 infection.
      OBJECTIVE: To test the hypothesis that HIV-1 seroconversion and disease
      progression are associated with changes in risk behaviours, using data from a
      cohort of Kenyan female sex workers (FSWs). METHODS: HIV-1-seronegative FSWs were
      enrolled in a prospective cohort study of risk factors for HIV-1 acquisition. At
      monthly visits, standardized interviews were conducted to assess sexual risk
      behaviour and HIV-1 serologic testing was performed. Seroconverters were invited
      to continue with follow-up. Between 1993 and 2004 (when antiretroviral therapy
      was introduced in the cohort), 265 women seroconverted for HIV-1 (incidence
      7.7/100 person-years) and were included in this analysis. RESULTS: Unprotected
      intercourse was reported at 546/2037 (27%) pre-seroconversion visits versus
      557/3732 (15%) post-seroconversion visits (P < 0.001). These findings remained
      significant after adjustment for potential confounding factors [adjusted odds
      ratio (AOR) 0.69; 95% confidence interval (CI), 0.55-0.86]. Compared with HIV-1
      seronegative women, there was a progressive stepwise decrease in unprotected
      intercourse among HIV-1-seropositive women with CD4 cell counts > or = 500 (AOR,
      0.93; 95% CI, 0.62-1.39), 200-499 (AOR, 0.58; 95% CI, 0.41-0.82) and < 200
      cells/microl (AOR, 0.45; 95% CI, 0.25-0.82). Decreases in unprotected intercourse
      reflected increases in both abstinence and 100% condom use. Women also reported
      fewer partners and fewer episodes of intercourse after HIV-1 seroconversion.
      CONCLUSIONS: HIV-1 seroconversion and disease progression were associated with
      decreases in sexual risk behaviour among Kenyan FSWs.

PMID- 16988520
TI  - "Nothing new": responses to the introduction of antiretroviral drugs in South
      Africa.
AB  - Interviews conducted in South Africa found that awareness of antiretroviral
      therapy was generally poor. Antiretroviral drugs were not perceived as new, but
      one of many alternative therapies for HIV/AIDS. Respondents had more detailed
      knowledge of indications, effects and how to access alternative treatments, which
      is bolstered by the active promotion and legitimization of alternative
      treatments. Many expressed a lack of excitement about the introduction of
      antiretroviral therapy, and little change in their attitudes concerning the
      epidemic.

PMID- 16988521
TI  - Unexpected drug-drug interaction between tipranavir/ritonavir and enfuvirtide.
AB  - Fifty-five patients placed on tipranavir/ritonavir 500/200 mg twice a day (27
      with enfuvirtide and 28 without) underwent tipranavir and ritonavir plasma
      concentration measurements by high-pressure liquid chromatography. Markedly
      higher tipranavir and ritonavir trough concentrations were observed in
      enfuvirtide recipients. The modelling of sparse plasma samples using a first
      order absorption and elimination monocompartmental model without time lag
      predicted higher tipranavir elimination half-life and volume of distribution in
      enfuvirtide takers. This unexpected drug-drug interaction warrants further
      investigation.

PMID- 16988522
TI  - Cardiac isoform of alpha 2 macroglobulin, an early diagnostic marker for cardiac
      manifestations in AIDS patients.
AB  - This study investigated the possible role of the cardiac isoform of alpha 2
      macroglobulin (CA2M) as an early diagnostic marker for HIV-associated
      cardiovascular manifestations. A total of 349 samples were analysed by Western
      blot and quantified by sandwich enzyme-linked immunosorbent assay. The levels of
      CA2M present in sera of HIV-associated cardiac diseases were significantly higher
      than those of HIV without cardiac involvement and healthy sera. CA2M may act as a
      novel diagnostic marker to identify cardiac manifestations in HIV/AIDS patients.

PMID- 16988523
TI  - Effects of infant sex on mother-to-child transmission of HIV-1 according to
      timing of infection in Zimbabwe.
AB  - We examined the relationship between sex and the risk of intrauterine,
      intrapartum and postnatal HIV transmission among 4495 infants born to HIV
      infected mothers in Harare, Zimbabwe. Intrauterine transmission was 8.6%, and
      consistent with other studies was higher among girl than boy infants (AOR 1.53;
      95% CI 1.23-1.91). Unlike previous studies, we observed no independent effect of
      infant sex on intrapartum or breastfeeding-associated HIV transmission. Sex
      specific postnatal prevention strategies are not warranted in this population.

PMID- 16988524
TI  - APOBEC3G genetic variants and their association with risk of HIV infection in
      highly exposed Caucasians.
AB  - The cytosine deaminase APOBEC3G has been identified as a host factor that
      inhibits HIV-1 replication. We investigated whether genetic variants of APOBEC3G
      that could potentially affect the protein's expression or function were
      associated with the risk of infection in 122 Caucasians highly exposed to HIV-1.
      A novel C40693T variant was significantly associated with an increased risk of
      infection, suggesting that there might be a role for APOBEC3G in susceptibility
      to HIV-1 infection that warrants further investigation.

PMID- 16988525
TI  - Response to "Atazanavir/ritonavir versus lopinavir/ritonavir: equivalent or
      different efficacy profiles?" by Hill.

PMID- 16988526
TI  - Drugs should be affordable to India's poor to fight HIV/AIDS.

PMID- 16988527
TI  - Crohn's disease onset in an HIV/hepatitis C virus co-infected woman taking
      pegylated interferon alpha-2b plus ribavirin.

PMID- 16988528
TI  - The role of tenofovir in the prevention of HIV infections.

PMID- 16988529
TI  - Response to Waters et al. "Successful use of genotypic resistance testing in HIV
      1-infected individuals with detectable viraemia ...".

PMID- 16988530
TI  - Off-label promotion.

PMID- 16988531
TI  - Surrogate endpoints and drug approval.

PMID- 16988532
TI  - IDA-FLAG regimen for the therapy of primary refractory and relapse acute
      leukemia: a single-center experience.
AB  - We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin,
      and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed
      acute leukemia patients. Patients were treated with fludarabine phosphate 25
      mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was
      given subcutaneously from sixth day until absolute neutrophil count (ANC)
      >500/microL. One third of the acute myeloblastic leukemia (AML) and 45% of acute
      lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML
      patients, complete remission (CR) was achieved in 15 cases (53.6%). One case
      showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this
      regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte
      recovery time was 16 days. Nonhematologic complications were mild to moderate
      nausea, vomiting, and mucositis and could be controlled by routine measures. Stem
      cell transplantation was performed in 5 patients and all achieved CR, 2
      autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8
      (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%)
      cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte
      recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting,
      and mucositis and could be controlled by supportive therapy. Autologous
      transplantation was performed in 1 patient, but relapse disease occurred after 5
      weeks. There was no correlation between response rate and leukemia subtype (AML
      versus ALL), leukocyte count, age, sex, disease status (de novo versus
      secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was
      16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3
      patients are alive and 2 of these are in continuous remission. The rest of the
      patients died. In conclusion, Ida-FLAG is a good choice in cases with
      refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a
      low-toxicity profile are preferable properties of this regimen, and this regimen
      has been found to be useful for cytoreduction, especially in candidates for allo
      SCT.

PMID- 16988533
TI  - Rise in prostate-specific antigen in men with untreated low-grade prostate cancer
      is slower during spring-summer.
AB  - To test the hypothesis that the rate of rise in prostate-specific antigen (PSA)
      is slower during the spring-summer than during the rest of the year, we used PSA
      data from a prospective single-arm cohort study of men who had been followed to
      characterize a watchful observation protocol with selective delayed intervention
      for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The
      rate of PSA increase was calculated as the visit-to-visit slope of log (PSA)
      against time, from 1 calendar-quarter visit to the next. The nonparametric
      Friedman test confirmed differences in rate of PSA rise among the calendar
      quarters (P = 0.041). Post hoc analysis showed the rate of PSA increase during Q2
      was significantly slower than in each one of the other calendar quarters (Q1
      versus Q2, P = 0.025; Q3 versus Q2, P = 0.002; Q4 versus Q2, P = 0.013), with no
      differences among quarters Q1, Q3, and Q4. These results are consistent with the
      vitamin D hypothesis that the higher 25-hydroxyvitamin D levels associated with
      spring and summer have a desirable effect on prostate biology. The therapeutic
      implication is that vitamin D supplementation in the range of 2000 IU/d, a dose
      comparable to the effect of summer, can benefit men monitored for rising PSA.

PMID- 16988534
TI  - Association of diet alone, insulin, sulfonylureas, metformin, and
      thiazolidinediones with the severity of coronary artery disease in patients with
      diabetes mellitus.
AB  - Coronary angiography was performed in 152 men and 163 women with diabetes
      mellitus, mean age 55 +/- 8 years, because of chest pain. Of 67 patients with 3
      vessel or 4-vessel coronary artery disease (CAD), 17 (25%) were treated with diet
      alone, 29 (43%) with insulin, 18 (27%) with sulfonylureas, 12 (18%) with
      metformin, and 6 (9%) with thiazolidinediones. Of 76 patients with 2-vessel CAD,
      20 (26%) were treated with diet alone, 36 (47%) with insulin, 21 (28%) with
      sulfonylureas, 21 (28%) with metformin, and 11 (14%) with thiazolidinediones. Of
      40 patients with 1-vessel CAD, 15 (38%) were treated with diet alone, 11 (28%)
      with insulin, 8 (20%) with sulfonylureas, 12 (30%) with metformin, and 4 (10%)
      with thiazolidinediones. Of 132 patients with 0-vessel CAD, 18 (14%) were treated
      with diet alone, 21 (16%) with insulin, 7 (5%) with sulfonylureas, 75 (56%) with
      metformin, and 35 (26%) with thiazolidinediones. Cochran-Armitage trend tests
      were used to examine whether the use of treatment significantly increases or
      decreases as the number of arteries with CAD increases (P = 0.036 for diet alone;
      P < 0.0001 for insulin, for sulfonylureas, and for metformin; P = 0.002 for
      thiazolidinediones).

PMID- 16988535
TI  - Emergency hemodialysis in the management of intoxication.
AB  - Management of intoxicated patients has many aspects in a wide spectrum, beginning
      with decontamination processes and basic supportive care. The most logical
      therapeutic approach is probably the specific antidotes, when available and/or
      applicable. On the other hand, many chemicals and drugs, can be removed from the
      body by means of hemodialysis or hemoperfusion while treating vital sign
      abnormalities and electrolyte and acid-base disturbances of the patient. In this
      paper, we describe 11 cases of intoxication, 6 with methyl alcohol, 3 with
      lithium, and 2 with salicylate, admitted to emergency department and treated with
      hemodialysis between January 1, 2002 and December 31, 2004. We review their
      medical charts and detailed demographic data, medical history, type of exposure,
      clinical and laboratory presentations, duration of hemodialysis performed, and
      the outcome.

PMID- 16988536
TI  - Using patient-centered endpoints to determine the cost-effectiveness of triptans
      for acute migraine therapy.
AB  - The objective of this study was to use the patient-centered efficacy measurements
      of sustained pain free and sustained pain free with no adverse events to compare
      the relative cost-effectiveness of 6 oral triptans in the treatment of acute
      migraine. Adverse event and sustained pain-free rates were obtained from a
      comprehensive meta-analysis of 53 clinical trials of oral triptans. Efficacy and
      tolerability were assumed to be independent. Average wholesale prices were in US
      dollars as of May 10, 2004. The meta-analysis of oral triptans reported that
      almotriptan 12.5 mg (Axert) exhibited the highest sustained pain-free rate
      (25.9%), with the lowest rate associated with eletriptan 20 mg (Relpax) (10.6%).
      In addition, almotriptan 12.5 mg possessed the lowest overall absolute adverse
      event rate (14.2%), with the highest adverse event rate exhibited by eletriptan
      80 mg (53.9%). To attain 100 sustained pain-free patients, almotriptan 12.5 mg
      and rizatriptan 10 mg (Maxalt) proved to be the most cost-effective triptans,
      costing $7120 and $7427, respectively; the least cost-effective were naratriptan
      2.5 mg (Amerge) ($13,736) and eletriptan 20 mg ($16,104). To attain 100 sustained
      pain-free with no adverse events patients, almotriptan 12.5 mg was the most cost
      effective triptan ($8298) and the least cost-effective were eletriptan 20 mg
      ($25,521) and eletriptan 80 mg ($29,614). At average wholesale prices as of May
      10, 2004, almotriptan 12.5 mg achieved the highest level of cost-effectiveness
      using either sustained pain free or sustained pain free with no adverse events as
      endpoints.

PMID- 16988537
TI  - Pharmacokinetics of an extended release formulation of alprazolam (Xanax XR) in
      healthy normal adolescent and adult volunteers.
AB  - The purpose of this study was to estimate pharmacokinetics, safety, and
      tolerability of single doses of an extended release formulation of alprazolam
      (Xanax XR) in adolescent and adult healthy volunteers. This was a randomized,
      open-label, single-dose, 2-period crossover study. Twelve adolescent healthy
      volunteers (13-17 years) and 12 adult healthy volunteers (20-45 years) received
      single doses of Xanax XR 1 mg or 3 mg tablets. Blood samples were obtained
      predose and for 48 hours postdose. Plasma samples were assayed for alprazolam and
      its two active metabolites alpha-hydroxy-alprazolam and 4-hydroxy-alprazolam
      using a validated LC-MS/MS method. Safety assessments included clinical
      laboratory tests, vital signs, and adverse event monitoring. At both dose levels,
      mean plasma concentration-time profiles of alprazolam, alpha-hydroxy-alprazolam,
      and 4-hydroxy-alprazolam were similar in adolescent and adult subjects. The
      ratios of estimated geometric means for AUC(0-infinity) and Cmax between
      adolescents and adults for both dose levels were 115% (95% CI: [93, 143]) and
      111% (95% CI: [95, 129]), respectively. An assessment of dose proportionality
      between the 3 mg and 1 mg alprazolam doses within both age groups indicated that
      the AUC(0-infinity) and Cmax were both within 80-125% equivalence limits. Parent
      metabolite ratios were similar in both age groups and were consistent with those
      previously reported. Alprazolam was well tolerated by both age groups. The most
      common adverse event was somnolence, which occurred in a dose-related manner.
      Based on the similar pharmacokinetic profiles, dosing of Xanax XR should be
      similar in adolescents and adults.

PMID- 16988538
TI  - Single-dose extended-release epidural morphine for pain following hip
      arthroplasty.
AB  - This open-label, serial-cohort pilot study evaluated DepoDur, a new, single-dose,
      extended-release epidural morphine (EREM) for pain control after hip
      arthroplasty. Single-dose EREM (10-30 mg) or a single dose of standard morphine
      sulfate (MS) (5 mg) was administered before surgery and spinal anesthesia. Among
      the 39 patients enrolled, total 48-hour supplemental fentanyl use was lower (P =
      0.011 overall treatment) and median time to first postoperative fentanyl use was
      three- to six-fold longer (P < 0.001 overall treatment), among 10-, 20-, and 30
      mg single-dose EREM patients versus MS patients. EREM patients reported higher
      levels of satisfaction with pain intensity scores comparable to MS patients.
      Safety results were similar between groups. Single-dose EREM was generally safe
      and effective for treating postoperative pain and reduced the need for
      supplemental analgesia.

PMID- 16988539
TI  - Effect of chloroquine on the bioavailability of ciprofloxacin in humans.
AB  - Chloroquine, a front-line drug in the treatment of malaria, has developed
      widespread resistance, especially to the Plasmodium falciparum strains.
      Ciprofloxacin is a second-generation quinolone used as a broad-spectrum
      fluoroquinolone antibacterial agent. The possibility of using ciprofloxacin as an
      antimalarial, especially in chloroquine-resistant strains, is very promising.
      They concluded from in vitro studies however that the anti-malarial effect occur
      at high dose level of ciprofloxacin to achieve the required serum concentrations.
      Studies have shown that there is little interstrain variability in the in vitro
      susceptibility of P. falciparum to fluoroquinolones. There is also no cross
      resistance between them. Another study stated that 50% inhibition of parasite
      growth in vitro required 6.6 microg/mL after a high dose of ciprofloxacin was
      used. They thus concluded that ciprofloxacin should not be used alone. There is
      need for in vivo studies to ascertain the achievable serum concentration of
      ciprofloxacin when given alone and when given in combination with chloroquine.
      The serum concentration of ciprofloxacin was studied when ciprofloxacin was given
      alone and in combination with chloroquine in humans. Five healthy male volunteers
      aged (19-31) years who were not taking any of the prescribed medications and had
      no sensitivity to either ciprofloxacin or chloroquine, each received 500 mg
      ciprofloxacin orally with 250 mL of water, and after a 2-week wash-out period,
      500 mg ciprofloxacin plus 600 mg of chloroquine was administered orally with 250
      mL of water after informed consent. A blood sample (2.5 mL) was collected just
      before taking the drug at 8:00 AM representing 0 hours and continued afterward at
      1, 2, 4, 8, 12, and 24 hours the following day. Serum samples were stored at -20
      degrees C until analyzed. The minimal inhibitory concentrations (MIC) by
      diffusion through agar technique was used for the assay of serum ciprofloxacin.
      The following bioavailability parameters: Cmax, tmax, and AUC 0-24, AUC 0
      infinity were calculated. The peak serum concentration Cmax of ciprofloxacin was
      3.42 +/- 0.32 microg/mL, which dropped to 2.8 +/- 0.18 microg/mL when chloroquine
      was taken together with ciprofloxacin. These values were less than the in vitro
      12.5 microg/mL concentrations required to inhibit P. falciparum. Though the
      effect of parasitemia was not ascertained, the in vivo use of ciprofloxacin alone
      or in combination is doubtful because increasing the dose that will reach the in
      vitro level will lead to toxicity in vivo.

PMID- 16988540
TI  - Effects of opioid prescription medication dependence and detoxification on pain
      perceptions and self-reports.
AB  - The purpose of this work is to document whether prescription opioid medications
      used for pain enhanced or worsened pain syndromes from medical conditions in
      patients who received a diagnosis of prescription opioid dependence as determined
      by a diagnosis by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV
      criteria. Further, whether detoxification improved or worsened pain perceptions
      and self-reports in patients who chronically administered prescription opioid
      medications. Our study consisted of a retrospective sample of patients taken from
      the Addiction Treatment Unit at St Lawrence Hospital in Lansing, MI. Patients
      were selected from those who voluntarily sought detoxification from opioid
      medications in an inpatient setting. Selection criteria for the study consisted
      of a DSM-IV diagnosis of opioid prescription medication dependence, willingness
      to undergo medical detoxification, cooperation with self-report scales, and
      abstinence from opioid medications. Study patients were randomly selected from
      discharges in patient census for the years 2001 to 2003. The significant findings
      were that self-reported pain scores improved during the detoxification from
      admission to discharge, from a mean of 5.5 at admission to mean of 3.4 at
      discharge (0 is no pain and 10 is the most pain). The detoxification period
      extended to an average of 5 days. Whereas oxycodone CR (OxyContin) produced
      higher levels of self-reported pain at admission than at discharge, and these
      patients experienced significant levels of pain reduction with decremental opioid
      doses as with other opioid medications. Patients with a DSM-IV diagnosis of
      prescription opioid dependence reported (self) less pain with detoxification and
      abstinence from the opioid medications.

PMID- 16988541
TI  - Neuroprotective therapy in Parkinson disease.
AB  - During the past decade, there has been a remarkable progress in our understanding
      of the biology of Parkinson disease (PD), which has been translated into
      searching for novel therapy for PD. Much focus is shifted from the development of
      drugs that only relieve PD symptoms to new generation of remedies that can
      potentially protect dopaminergic neurons and modify the disease course. Several
      novel therapeutic approaches have been tested in preclinical experiments and in
      clinical trials, including molecules targeting on genes involved in the
      pathogenesis of the disease, neurotrophic factors critical for dopaminergic
      neuron survival and function, new generation of dopamine receptor agonists that
      may possess neuroprotective effects, and agents of antioxidation,
      antiinflammation, and antiapoptosis. The results of these studies will shed new
      light to our hope that PD can be cured in the future.

PMID- 16988542
TI  - Regression of grade III astrocytoma during the treatment of CML with imatinib
      mesylate.
AB  - Astrocytomas are central nervous system neoplasms, which are derived
      predominately from astrocytes. On the basis of the histopathologic
      characteristics astrocytomas are graded from I to IV. The cells that demonstrate
      the greatest degree of anaplasia are used to determine the histologic grade of
      the tumor. The mean age of survival are approximately 10 years from the time of
      diagnosis for pilocystic astrocytomas (World Health Organization grade I), more
      than 5 years for patients with low-grade diffuse astrocytomas (WHO grade II), 2
      to 5 years for those with anaplastic astrocytomas (WHO grade III), and less than
      1 year for patients with glioblastoma (WHO grade IV). The treatment is a
      combination of surgery, radiation, and chemotherapy depending of the grade of
      astrocytoma. We present a case of 31-year-old man with grade III astrocytoma with
      subsequent chronic myelogenous leukemia treated with imatinib mesylate as part of
      his chronic myelogenous leukemia treatment failing to show recurrence of the
      astrocytoma 10 years after standard treatment for astrocytoma.

PMID- 16988543
TI  - Infective endocarditis of native valve after anterior nasal packing.
AB  - We present a case report of a patient who was previously treated for spontaneous
      epistaxis with a petroleum jelly gauze (0.5 in x 72 in) anterior nasal packing
      filled with an antibiotic ointment, along with prophylactic oral clindamycin. The
      patient presented with fever and hypotension 3 days after the nasal packing. Her
      blood cultures grew methicillin-resistant Staphylococcus aureus and the
      transesophageal echocardiography showed vegetation on the atrial surface of the
      posterior mitral valve leaflet, confirming the diagnosis of bacterial
      endocarditis attributable to nasal packing. Several case reports discuss toxic
      shock syndrome after nasal packing, but none describe endocarditis of the native
      heart valves subsequent to anterior nasal packing. Current guidelines on
      endocarditis prophylaxis produced by the American Heart Association, European
      Cardiac Society, and British Cardiac Society together with published evidence do
      not recommend endocarditis prophylaxis for patients with native heart valves
      undergoing anterior nasal packing.

PMID- 16988544
TI  - Quality and reliability of routine coagulation testing: can we trust that sample?
AB  - Poor standardization of preanalytic variables exerts a strong influence on the
      reliability of coagulation testing, consuming valuable health care resources and
      compromising patient outcome. Most uncertainties emerge from patient
      misidentification and the procedures for specimen collection and handling.
      Location of unsuitable venous access or problematic phlebotomies may produce
      spurious activation of the hemostatic system and hemolytic specimens. Prolonged
      venous stasis is associated with hemoconcentration and spurious variations of
      most coagulation assays. Additional pitfalls can be introduced by inappropriate
      phlebotomy tools and small-gauge needles. Inappropriate filling and mixing of the
      tube, unsuitable procedures for centrifugation and storage of the specimens are
      additional aspects that need accurate standardization. Besides traditional
      preanalytic variables affecting routine coagulation testing, thrombin-generation
      assays require specific criteria to be accurately fulfilled. These aspects
      include the type of specimen (platelet-poor plasma, platelet-rich plasma or whole
      blood), blood collection tubes, storage conditions and the presence of residual
      platelets. Compliance with new international quality assessment programs, which
      will also involve coagulation laboratories, encompasses the adoption of suitable
      strategies for reducing undue variability throughout the whole testing process.
      Such strategies would not entail extraordinary costs and are affordable with a
      structured outlay of existing resources, educational policies and compliance with
      reliable guidelines.

PMID- 16988545
TI  - A systematic review of antithrombin concentrate use in patients with disseminated
      intravascular coagulation of severe sepsis.
AB  - The objective was to estimate the effect of antithrombin therapy on mortality in
      disseminated intravascular coagulation (DIC) of severe sepsis and septic shock.
      Randomized clinical trials (RCT) on patients with DIC and severe sepsis or septic
      shock assigned to intravenous antithrombin or placebo were searched. Eligible
      studies reported death as the outcome measure. Of 35 RCT, 32 trials were excluded
      because patients were not randomized to antithrombin versus placebo, or no
      separate data on patients with DIC were given. In three RCT, 364 patients with
      severe sepsis or septic shock and DIC were randomized. The disease severity,
      definition of DIC, dose and duration of treatment varied among the trials. In two
      of the three RCT, data were from subgroup analyses (patients not stratified by
      DIC). The combined odds ratio for short-term all-cause mortality in those who
      received antithrombin was 0.649 (95% confidence interval, 0.422-0.998). Data on
      bleeding complications in patients treated with antithrombin were reported only
      in one of the RCT and were not considered suitable for systematic safety
      estimation. In sepsis patients with DIC, administration of antithrombin
      concentrate may increase overall survival. Current available evidence, however,
      is not suited to sufficiently inform clinical practice.

PMID- 16988547
TI  - The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous
      thromboembolism?
AB  - The substitution of leucine for valine at amino acid position 34 of the factor
      XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous
      leucine/leucine genotype has been reported to confer protection against venous
      thromboembolism, but previous studies have not evaluated a population limited to
      those with idiopathic venous thromboembolism. The primary objective of the study
      was to determine whether the FXIII Val34Leu polymorphism is independently
      associated with the occurrence of idiopathic venous thromboembolism. We
      prospectively enrolled consecutive patients with at least one objectively
      confirmed idiopathic venous thromboembolism. Friends of cases were recruited as
      controls and matched to cases by sex, ethnicity, and age. All participants were
      tested for the FXIII Val34Leu polymorphism in addition to several well-known
      thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII
      leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An
      adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for
      the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the
      dominant model. Our results do not support an independent association of the
      FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our
      Caucasian Canadian study population.

PMID- 16988546
TI  - The tissue factor pathway in ischemic stroke.
AB  - To explore the role of the the tissue factor (TF) pathway in ischemic stroke. We
      measured blood concentrations of markers of the TF pathway [TF antigen, free
      tissue factor pathway inhibitor antigen (TFPIf) and activity (TFPIac), and
      activated factor VII (FVIIa)] within 7 days (acute phase) and after 3-6 months
      (convalescence) in 150 patients with first-ever ischemic stroke and 150 community
      controls. During the acute phase, TF antigen and TFPIf were not significantly
      altered but TFPIac was increased (mean 1.27 versus 1.13 U/ml, P = 0.04) and FVIIa
      was decreased in cases compared with controls (mean 43.3 versus 57.9 mU/ml, P =
      0.0004). After adjusting for baseline differences between cases and controls,
      increasing quartiles of TFPIf were independently associated with reduced odds of
      stroke, and reducing quartiles of FVIIa and increasing quartiles of TFPIac with
      increased odds of stroke. During the convalescent phase, FVIIa and TFPIac
      returned to normal but TF antigen and TFPIf were significantly decreased compared
      with controls [median TF antigen, 110 (follow-up) versus 155 pg/ml (controls), P
      = 0.0008; median TFPIf, 15.5 (follow-up) versus 23.3 ng/ml (controls), P =
      0.002]. Alterations of blood concentrations of TF pathway markers are common in
      patients with acute ischemic stroke. The mechanisms are unclear but may relate to
      enhanced formation of TF-FVIIa complexes and upregulation and release of TFPI
      during the acute phase, and ongoing consumption of TF antigen and TFPIf during
      the chronic phase as the atherosclerotic plaque heals.

PMID- 16988548
TI  - Identification of plasma antifibrin/fibrinogen antibodies in a patient with
      hemolytic uremic syndrome.
AB  - We investigated a patient with atypical hemolytic uremic syndrome without
      diarrhea to determine the presence of antibodies and the specificity of the
      related antigens. The patient experienced repeated episodes of hemolytic uremic
      syndrome. She is dialysis dependent. von Willebrand factor (vWF), vWF multimers,
      platelet aggregation, ADAMTS-13 activity and platelet immunoblots were
      determined. During acute episodes vWF increased threefold, with unusually large
      vWF multimers on two occasions. Platelet aggregation was normal but the plasma
      caused spontaneous aggregation of normal platelets. Reactivity was removed after
      absorption with protein A. Protein blotting against platelet and microvascular
      endothelial cells showed strong and persistent reactivity against antigens of 200
      and 55 kDa. Two-dimensional immunoblots of the whole platelet proteome and
      incubation with plasma identified strong immunoreactivity with two target spots
      in the 55-kDa area. Mass spectroscopy confirmed the target as beta-fibrin,
      molecular weight 50.73 kDa, isoelectric point 7.95, with MASCOT scores of 859 and
      750, Two years after presentation another band was detected at 66 kDa and
      identified as the alpha subunit of fibrin. This patient's plasma contained a
      platelet-aggregating factor that was removed by immunoglobulin absorption. She
      developed antibodies against the alpha and beta subunits of fibrin/fibrinogen.

PMID- 16988549
TI  - Global assessment of the coagulation status in type 2 diabetes mellitus using
      rotation thromboelastography.
AB  - Clinical and epidemiologic observations have led to the concept of a procoagulant
      state in type 2 diabetes. This study aimed to determine the coagulation status in
      type 2 diabetic patients using rotation thromboelastography (ROTEM), which
      measures the interactive dynamic coagulation process. For this purpose, 51 (30
      women, 21 men) type 2 diabetic patients (mean age, 56.1 years) and 40 age
      matched, sex-matched and body-mass-index-matched healthy individuals were
      enrolled. Twenty-seven of the diabetic group had diabetic vascular complications.
      ROTEM using different activators for the intrinsic and extrinsic systems of
      coagulation cascade (intrinsic TEM-INTEM, extrinsic TEM-EXTEM, FIBTEM) was used
      to measure the coagulation time (CT), clot formation time (CFT), alpha angle
      (alpha) and maximum clot firmness (MCF). No significant difference was found in
      the prothrombin time, partial thromboplastin time, thrombin time, fibrinogen and
      platelet count between the two groups. INTEM-CT and INTEM-CFT and EXTEM-MCF were
      significantly higher in the diabetic group compared with controls (P = 0.012, P =
      0.007 and P = 0.029, respectively). INTEM alpha in the diabetic group was
      significantly lower than the controls (P = 0.001). All other parameters,
      including INTEM-MCF, EXTEM-CT, EXTEM-CFT, EXTEM-alpha, FIBTEM-CT, FIBTEM-CFT,
      FIBTEM-MCF and FIBTEM-alpha, were similar between the two groups. Taking into
      account these data, we conclude that there is subtle activation of the extrinsic
      pathway with a concomitant decrement in the intrinsic pathway of the coagulation
      cascade in type 2 diabetes. The exact underlying mechanisms leading to these
      changes, and their consequences with regard to diabetic complications, remain to
      be determined.

PMID- 16988550
TI  - A metabolic syndrome independent association between overweight, fibrinolysis
      impairment and low-grade inflammation in young women with venous thromboembolism.
AB  - It is known that overweight induces fibrinolysis impairment. Since this
      association has not been completely explored in patients with venous
      thromboembolism (VTE), we aimed to investigate its presence in young women with
      VTE and, if present, to determine its extent and the factors that influence it.
      Thirty women aged 23-49 years in the stable period after VTE were included [19
      overweight (body mass index > or = 25) and 11 normal weight]; 52 healthy women
      (27 overweight and 25 normal weight) served as controls. The euglobulin clot
      lysis time (ECLT), plasminogen, D-dimer, tissue-type plasminogen activator (t-PA)
      and plasminogen activator inhibitor-1 (PAI-1) antigen and activity, lipids,
      fasting plasma glucose, insulin, fibrinogen, interleukin-6 and sedimentation rate
      were compared between the groups. Overweight patients had more impaired
      fibrinolysis (delayed ECLT, higher PAI-1 and t-PA antigen) than overweight
      controls (and normal weight patients). There was no difference in levels of
      insulin, glucose, fibrinogen and interleukin-6, whereas the sedimentation rate
      was significantly elevated in overweight patients compared with overweight
      controls [16 (8-31) versus 8 (5-12), P < 0.05]. The sedimentation rate in
      overweight patients significantly correlated with body mass index, ECLT, t-PA and
      PAI-1 antigen, but not with fibrinogen or interleukin-6. We found that overweight
      VTE patients have more prominent fibrinolysis impairment than predictable from
      parameters of metabolic syndrome and that is associated with an elevated
      sedimentation rate. This association could represent a new thrombotic risk
      profile in overweight women.

PMID- 16988551
TI  - Influence of the needle bore size on platelet count and routine coagulation
      testing.
AB  - The phlebotomy technique, particularly the use of small-bore needles, may
      influence the reliability of coagulation testing and platelet count. Routine
      coagulation tests were assayed in blood specimens collected from 22 consecutive
      patients in three separate, sequential phlebotomies, using butterfly devices with
      different needle sizes. Test results of samples collected with 23 and 25 G
      needles were compared with those obtained with the currently recommended 21 G
      needle. Although both the prothrombin time and activated partial thromboplastin
      time displayed a trend towards lower values employing the smaller 23 and 25 G
      needles, results did not differ significantly from the reference 21 G needle
      specimen, with the exceptions of D-dimer (25 G versus 21 G needle, 186 +/- 70
      versus 178 +/- 66/ml, P < 0.01) and platelet count (23 G versus 21 G needle, 246
      +/- 55 versus 254 +/- 56 x 10(-3)/l, P < 0.01; 25 G versus 21 G needle, 240 +/-
      55 versus 254 +/- 56 x 10(-3)/l, P < 0.01). None of the mean biases recorded for
      the parameters was clinically meaningful, nor did they exceed the current
      desirable analytical quality specifications for desirable bias. Results of the
      present investigation suggest that, when a proper technique is used and within
      certain limitations, butterfly devices with small-bore needles may be a reliable
      alternative to draw venous blood for platelet count and coagulation testing.

PMID- 16988552
TI  - Fibrinolytic response to exercise in women using third-generation oral
      contraceptives.
AB  - The use of oral contraceptives (OC) is associated with an increased risk of
      thrombosis, suggesting OC exert procoagulant and/or antifibrinolytic effects.
      Given that physical exercise physiologically leads to an activation of blood
      coagulation and fibrinolysis, this study tested the hypothesis that OC might
      compromise the fibrinolytic response to exercise. Fibrinolytic variables were
      measured in 10 women (24 +/- 2 years) using OC (a formulation containing 30 micro
      g ethinylestradiol and 150 micro g desogestrel) and in 11 women without OC (mean
      +/- SD, 27 +/- 3 years) before, during and after a 1-h run on a treadmill at a
      velocity corresponding to an oxygen demand of 75-80% of maximum (anaerobic
      threshold). Exercise testing gave rise to considerable increases of tissue-type
      plasminogen activator antigen by seven-fold to eight-fold in women taking and not
      taking OC alike. In the presence of unchanged plasma levels of plasminogen
      activator inhibitor-1, exercise-induced release of tissue-type plasminogen
      activator led to enhanced plasmin formation with respect to plasmin-antiplasmin
      complexes, rising by (mean +/- standard error) 701 +/- 77 ng/ml (P < 0.001) in
      women using OC and by 695 +/- 117 ng/ml (P < 0.001 versus baseline; NS versus OC
      users) in controls. The fibrinolytic response to intensive physical exercise is
      preserved in women using OC and is similar to women not using OC.

PMID- 16988553
TI  - Global fibrinolytic capacity in pediatric patients with sepsis and disseminated
      intravascular coagulation.
AB  - There are many complex pathophysiologic changes of the coagulation system in
      sepsis. The fibrinolytic system was evaluated in septic children using the global
      fibrinolytic capacity (GFC), a new technique reflecting the overall fibrinolytic
      activity. The study consisted of 24 children with sepsis, 36 children with sepsis
      plus disseminated intravascular coagulation (DIC), and 20 healthy age-matched
      control individuals. Compared with controls, 86% of sepsis patients and 87% of
      sepsis plus DIC patients had decreased GFC levels. Between the sepsis plus DIC
      and sepsis groups there was no significant difference in terms of GFC levels.
      While 19 patients (52.7%) died in the sepsis plus DIC group, only three patients
      (12.5%) died in the sepsis group. When survivors and nonsurvivors were compared
      in terms of coagulation tests, there were significant differences for protein C,
      antithrombin, platelet, fibrinogen, aspartate aminotransferase, alanine
      aminotransferase, prothrombin time, and white blood cell values. In conclusion,
      the level of GFC reduced in most of the pediatric sepsis patients but no
      difference was observed between patients with sepsis and patients with sepsis
      plus DIC. While inhibition of fibrinolysis is an important finding in sepsis, the
      mortality is mainly associated with the presence of end-organ damage and the
      status of coagulation parameters.

PMID- 16988554
TI  - A novel assay for factor XIII based on cross-linking of synthetic peptides:
      analysis of different substrates.
AB  - A novel assay for factor XIII is described that utilizes exclusively small
      synthetic peptides as substrates for the cross-linking reaction catalyzed by
      activated factor XIII (FXIIIa). The acyl donor substrate (selection peptide) is
      immobilized on a microplate via biotin while the acyl acceptor substrate
      (detection peptide) is labeled with the fluorochrome Oregon green to allow
      sensitive detection without the need for secondary enzyme systems for signal
      amplification. Starting with an amino acid sequence from the fibrin gamma-chain
      (GQQHHLGGAKQAGDV) as a prototype peptide, the influence of amino acid exchanges
      were investigated with respect to their impact on the FXIIIa-catalyzed reaction.
      It was found that FXIIIa readily accepts a broad range of substrate peptides,
      with a proline neighboring the essential lysine having the most detrimental
      effect. The assay appears to be valuable for the molecular characterization of
      factor XIII and may be used for a deeper investigation into the substrate
      requirements of this final enzyme of wound repair, and eventually also for the
      characterization of other transglutaminases.

PMID- 16988555
TI  - Acute myocardial infarction following an arthropod bite: is hereditary
      thrombophilia a contributing factor?
AB  - Acute myocardial infarction (AMI) due to arthropod envenomation has rarely been
      reported in the literature. In the present report, we describe two cases who
      developed AMI following an arthropod bite. Coronary angiograms revealed normal
      coronary arteries in both patients. Both events were probably secondary to
      coronary artery thrombosis and/or coronary artery vasospasm. Both patients were
      subsequently found to be heterozygous for prothrombin mutation (G20210A). As a
      result, we recommend ruling out the possibility of hereditary thrombophilias in
      young patients with AMI developing after an arthropod bite.

PMID- 16988556
TI  - Factor V inhibitor: case report.
AB  - Acquired inhibitors to coagulation factors are rare, certainly those directed
      against factor V. A total of around 150 cases have so far been reported, of which
      the greater part was due to bovine thrombin exposure. We report the case of a
      patient who developed a factor V inhibitor during a postoperative period. This
      report describes possible aetiologies, varying clinical conditions and treatment
      possibilities as described in the literature. Furthermore, this case report is an
      example of the often unpredictable disease progression in a patient with
      existence of a factor V inhibitor.

PMID- 16988557
TI  - A successful treatment of life-threatening bleeding from polycystic kidneys with
      antifibrinolytic agent tranexamic acid.
AB  - We describe a successful treatment of a severe, persistent bleeding from both
      kidneys in a patient with autosomal dominant polycystic kidney disease (ADPKD)
      with tranexamic acid (TXA), a potent antifibrinolytic agent. The bleeding could
      not be controlled by intensive conservative treatment, it became life-threatening
      and urgent bilateral nephrectomy was intended. Since local and systemic
      hyperfibrinolysis play a role in bleeding in ADPKD patients, we tried TXA
      treatment. In fact, the massive bleeding promptly stopped, and haematuria
      gradually ceased. Removal of both kidneys was prevented. After 5 days both
      ureters became obstructed by blood clots, but placing J-catheters in each pyelon
      successfully solved this complication. Our case shows that it is reasonable to
      try antifibrinolytic treatment with TXA in such devastating uncontrolled
      bleeding.

PMID- 16988558
TI  - Platelet factor V supports hemostasis in a patient with an acquired factor V
      inhibitor, as shown by prothrombinase and tenase assays.
AB  - A woman with gross hematuria was shown to have a severe isolated factor V
      deficiency due to a factor V inhibitor of 200 U/ml titer. Hematuria persisted
      despite multiple infusions of plasma but, after one transfusion with 1 U
      platelets, urine red blood cells decreased by more than 98%. To evaluate the
      patient's platelet function we performed prothrombinase and tenase assays with
      platelets from the patient and from normal donors. By prothrombinase assay,
      ionophore-activated patient platelets showed 42% of the activity of normal
      platelets in their ability to support prothrombin activation by activated factor
      X; whereas in a 'tenase' assay, which measures the platelets' ability to support
      factor X activation by activated factor IX + activated factor VIII, their
      activity was 117% of normal. The addition of excess bovine activated factor V to
      the prothrombinase assay fully corrected the defect. The results demonstrate the
      benefit of platelet transfusion and indicate that in this case the platelets are
      the primary source of factor V for hemostasis.

PMID- 16988559
TI  - Abnormal melt curve profile during prothrombin 20210G --> A analysis due to the
      20209C --> T variant.
AB  - The common factor II 20210G --> A mutation, located in the 3'-untranslated
      region, is an important risk factor for the development of thromboembolic
      disorders, especially in Caucasians. A number of methods are employed for
      clinical laboratory diagnosis of this mutation, some of which are capable of
      detecting adjacent 3'-end sequence variations. We present results from an African
      deep vein thrombosis patient tested for the 20210G --> A mutation by real-time
      polymerase chain reaction and melt-curve analysis using hybridization probes that
      incidentally detected an adjacent 3'-untranslated region variant. The patient
      sample was tested using the Factor II (Prothromobin) G20210A Kit (Roche
      Diagnostics, Indianapolis, Indiana, USA), in conjunction with the Roche
      LightCycler. A polymerase chain reaction fragment from the 3'-end of the F2 gene
      was subsequently sequenced for identification of the variant. Melt-curve analysis
      revealed a normal 20210*G peak and an unknown aberrant allelic peak. Following
      sequence analysis, the patient was determined to be heterozygous for 20209C -->
      T. The presence of the 20209C --> T variant in the current patient and in eight
      other reported individuals of African descent, most with thrombosis-associated
      complaints, suggests that this rare variant poses a potential increased risk for
      thromboembolic disease in this ethnic group.

PMID- 16988560
TI  - Tissue plasminogen activator and thrombin generation measurements using the
      Thrombinoscope.

PMID- 16988561
TI  - Estimated costs of prescription opioid analgesic abuse in the United States in
      2001: a societal perspective.
AB  - OBJECTIVES: This study estimates the costs to society of prescription opioid
      analgesic (RxO) abuse in the United States. METHODS: Costs associated with RxO
      abuse were grouped into healthcare, criminal justice, and workplace categories.
      Costs were estimated by either (1) a quantity method that multiplies the number
      of RxO abusers derived from various national surveys by the estimated per abuser
      cost, or (2) an apportionment method that starts with overall (ie, prescription
      and nonprescription) drug abuse costs for a cost component (eg, police
      protection) and apportions the share of costs based on the prevalence of RxO
      abuse relative to overall drug abuse. Medical costs in excess of those for
      otherwise similar nonabusers were based on an analysis of a large administrative
      claims database for an employed population using multivariate regression methods.
      RESULTS: A lower bound estimate of the costs of RxO abuse in the United States
      was 8.6 billion dollars in 2001 (or 9.5 billion dollars in 2005 dollars). Of this
      amount, 2.6 billion dollarswere healthcare costs, 1.4 billion dollars were
      criminal justice costs, and 4.6 billion dollars were workplace costs.
      CONCLUSIONS: The costs of RxO abuse represent a substantial economic burden.
      Rising trends of RxO abuse suggest an escalating economic and public health
      burden in coming years in the United States, and potentially, elsewhere.

PMID- 16988562
TI  - Sumatriptan alleviates pain in patients with trigeminal neuralgia.
AB  - OBJECTIVES: Arterial compression of the trigeminal root may lead to trigeminal
      neuralgia. 5-HT1B/1D receptor agonists may inhibit vasodilation and inflammation
      near the irritated trigeminal root. A recent study showed attenuation of
      mechanical allodynia by a 5-HT1A receptor agonist in a rat model of trigeminal
      neuralgia. The present study examined the effectiveness of a 5-HT1A/1B/1D
      receptor agonist, sumatriptan, on pain relief in patients with trigeminal
      neuralgia. METHODS: The study was conducted in 15 patients with idiopathic
      trigeminal neuralgia. The patients had been suffering from painful paroxysms for
      at least 1 month. Each patient was injected with 1 mL of saline subcutaneously
      (placebo), followed 15 minutes later with subcutaneous sumatriptan (3 mg in 1 mL
      saline). This was followed the next day by oral sumatriptan (50 mg twice daily)
      for 1 week. RESULTS: The visual analog scale did not change after saline, but
      significantly decreased after subcutaneous sumatriptan. Both 1 week after oral
      sumatriptan and 1 week after discontinuation of the drug, visual analog scale
      scores resulted in a significant decrease from the baseline. Adverse events after
      subcutaneous sumatriptan occurred in 4 patients: fatigue in 4 and nausea in 2.
      Side effects from the oral medication appeared in 4 patients: fatigue in 2,
      nausea in 1 and chest discomfort in 1. These side effects subsided soon after
      discontinuation of sumatriptan. CONCLUSIONS: Our results indicate that
      subcutaneous injection followed by oral administration of sumatriptan produces
      prompt and continuous analgesia in patients with trigeminal neuralgia.

PMID- 16988563
TI  - Sleep impairment in patients with painful diabetic peripheral neuropathy.
AB  - OBJECTIVE: This study evaluated sleep impairment associated with painful diabetic
      peripheral neuropathy (DPN), a neuropathic pain condition. Sleep is of critical
      concern for DPN because sleep impairment and its comorbidities may influence type
      2 diabetes progression. METHODS: This is a supplemental analysis of sleep data
      from a burden of illness study of patients with painful DPN (N=255, 61+/-12.8 y
      old, 51.4% women). Sleep was evaluated using the Medical Outcomes Study Sleep
      measure (MOS-Sleep). MOS-Sleep scores were compared with general population norms
      (N=1011), the MOS chronic disease sample (N=3445), and patients with postherpetic
      neuralgia (N=89). The MOS-Sleep Sleep Adequacy score was compared with data from
      the MOS diabetes subsample (N=590). RESULTS: Patients with painful DPN reported
      impaired sleep relative to the general population (P<0.001), the chronic disease
      sample (P<0.001), and postherpetic neuralgia patients (P<0.05). Self-rated MOS
      Sleep Sleep Adequacy was significantly less for the painful DPN than for the
      diabetes sample (P<0.001), although self-reported hours of sleep were not
      significantly different. Multiple regression indicated that age, average daily
      pain, and anxiety and depression symptom levels were each significantly (P<0.01)
      associated with, and collectively accounted for, 47% of variance in the MOS-Sleep
      Sleep Problems Index. DISCUSSION: Painful DPN is associated with considerable
      sleep impairment. Given the recognized association between sleep impairment, type
      2 diabetes and metabolic and affective disturbance, and the known adverse impact
      of affective disturbance on diabetes self-care, addressing these features-pain,
      sleep, and affective disturbance-is an important aspect of care for patients with
      painful DPN.

PMID- 16988564
TI  - Electrodermal responses to words in chronic low back pain patients: a comparison
      between pain descriptors, other emotional words, and neutral words.
AB  - OBJECTIVE: This study examines the electrodermal reactivity of chronic sufferers
      to emotional words. The hypothesis that patients are over-sensitive to pain
      descriptors is tested. METHODS: Electrodermal activity was recorded in 12 chronic
      low back pain patients and 12 healthy controls during passive viewing of words on
      a video monitor. These words were pain descriptors, other emotional words, and
      neutral words, in a pseudo-randomized order. A jingle was associated with the
      word occurrence. RESULTS: In chronic low back pain patients, skin conductance
      responses (SCRs) induced by pain descriptors or other emotional words were larger
      than SCRs induced by neutral words but they did not differ from each other.
      Patients presented SCRs, which were both larger and faster than those of
      controls, including following neutral words. There was no significant effect of
      word type in controls. Skin conductance level and the number of nonspecific
      fluctuations were larger in patients as compared with controls. CONCLUSIONS: The
      present electrodermal study suggests that chronic pain is linked to an increased
      reactivity to a wide range of stimuli. Emotional load amplifies the effect. This
      leads to recommend broad therapeutic management in chronic sufferers. Contrary to
      expectation derived from classical conditioning, patients did not prove over
      sensitive to pain descriptors. This negative finding is discussed at
      methodologic, physiologic, and psychologic levels.

PMID- 16988565
TI  - Is pain ever "normal"?
AB  - This article analyzes the Pain Terminology adopted by the International
      Association for the Study of Pain (IASP), noting that most of their pain
      categories are defined in terms of a reference standard of "normal" pain. Given
      the lack of any officially adopted operational definition of the word "normal,"
      we argue that the use of this word expresses and maintains a paradigm that drives
      many clinicians' reasoning about their patients' pain. We offer evidence that
      this uninterrogated paradigm is being tacitly used to differentiate legitimate
      pain reports from malingering and drug seeking. We consider this unsubstantiated
      "folk" sense of "normal" in light of evidence-based, rationalized prototypes
      based on statistical analysis of empirical evidence. We conclude that evidence
      for consistency in the experience and expression of pain and for clinician
      accuracy in evaluating the veracity of that pain is lacking; therefore, the
      logical preconditions needed for a rationalized, evidence-based prototype of
      "normal" pain have yet to be met. We conclude that the use of "normal" as a
      reference standard leads to ineffective and inhumane management of patient pain
      and to the danger that third parties, such as insurance companies and drug
      enforcement agencies, will use this unsubstantiated reference standard to
      arbitrarily limit pain therapy options. The authors recommend that the word
      "normal" be expunged from the International Association for the Study of Pain,
      Pain Terminology.

PMID- 16988566
TI  - A cost-utility analysis of chronic spinal pain treatment outcomes: converting SF
      36 data into quality-adjusted life years.
AB  - OBJECTIVES: The present retrospective case review study sought to analyze the
      cost-utility, expressed in cost/quality-adjusted life years (QALY), of current
      chronic spinal pain treatments. In addition, it expands upon previously published
      data evaluating the efficacy of interdisciplinary pain management in relation to
      medication management. METHODS: A recently developed algorithm was used to
      calculate QALYs using SF-36, v. 1 responses for 121 patients receiving treatment
      for chronic spinal pain at a pain rehabilitation center. Treatment groups
      evaluated were: (1) interdisciplinary program completers who received medication
      management and supplementary anesthetic procedures; (2) interdisciplinary program
      completers receiving medication management but not anesthetic procedures; (3)
      patients receiving medication management alone; and (4) patients receiving
      medication management with supplemental anesthetic procedures. Assessments were
      conducted at pretreatment and 6 months after the initiation of treatment.
      RESULTS: One-way analyses of covariance indicated that patients who participated
      in an interdisciplinary pain management program, which included medication
      management, psychotherapy, group education, and physical therapy, reported
      significantly less impairment in daily activities of living, less subjective
      experience of pain, and a higher quality of life and more preferred health state
      at the completion of their treatment phase, relative to patients receiving
      medication with or without anesthetic procedures. In addition, improvements in
      all outcome measures between pretreatment and posttreatment were significantly
      greater for those patients completing the interdisciplinary component of
      treatment. Cost-utility analyses revealed that the interdisciplinary treatment
      alone group was cost-saving, relative to the medication and procedures
      alternative, suggesting the former modality was both less costly and more
      effective than the latter. DISCUSSION: Average cost-utility ratios for both
      interdisciplinary treatment groups, ranging from 57,627 dollars /QALY to 75,885
      dollars /QALY, were within established cost-effective parameters (20,000 dollars
      to 100,000 dollars /QALY, generally considered a good value), whereas cost
      utility ratios for the standard care treatment groups were not interpretable
      because of a decrease in QALYs from pretreatment to posttreatment.

PMID- 16988567
TI  - Validation of a measure of protective parent responses to children's pain.
AB  - OBJECTIVES: To assess the validity of the Protect Scale of the Adult Responses to
      Children's Symptoms (ARCS) Questionnaire with regard to mothers' responses to
      their children's abdominal pain. METHODS: Mothers with High (n=32) and Low (n=35)
      Protect scores on the ARCS questionnaire were recruited from participants in a
      larger study of family illness behavior. Mothers completed a 28-day diary report
      of responses to their children's abdominal pain episodes. Records of their
      children's annual health service utilization and costs were obtained from their
      health maintenance organization (HMO). RESULTS: Mothers' scores on the ARCS
      Protect Scale were significantly correlated with their subsequent diary reports
      of protective responses to their children's abdominal pain. Compared to children
      of mothers in the Low Protect group, children of mothers in the High Protect
      group made significantly more health care visits for gastrointestinal symptoms
      and had significantly higher health care costs. CONCLUSIONS: Results supported
      the validity of the Protect Scale of the ARCS and demonstrated that mothers'
      protective responses to children's abdominal pain complaints at home predicted
      subsequent health service use for gastrointestinal symptoms.

PMID- 16988568
TI  - Prevalence of musculoskeletal disorders is systematically higher in women than in
      men.
AB  - OBJECTIVES: Many studies report a higher prevalence of musculoskeletal pain in
      women than in men. This paper presents an overview of sex differences in
      musculoskeletal pain with specific attention for: different parameters for
      duration of musculoskeletal pain (ie, 1-y period prevalence, point prevalence,
      prevalence of chronic pain, and prevalence of persistent chronic pain); and (2)
      different anatomic pain sites. METHODS: For the analyses, data from 2 general
      population-based prospective surveys (Dutch population-based Musculoskeletal
      Complaints and Consequences Cohort study and Monitoring Project on Risk Factors
      for Chronic Diseases-study) were used. The study population consisted of persons
      aged 25 to 64 years living in the Netherlands. Data on self-reported pain
      complaints were assessed by written questionnaires. RESULTS: The results of this
      study showed that prevalence rates of musculoskeletal pain were higher for women
      than for men in the Dutch general population aged 25 to 64 years on the basis of
      2 population-based surveys. For musculoskeletal pain in any location, 39% of men
      and 45% of women reported chronic complaints. Highest female predominance was
      found for the hip and wrist/hand, whereas lowest and not statistically
      significant sex differences were found for the lower back and knee. All duration
      parameters of musculoskeletal pain showed a female predominance of
      musculoskeletal pain (1-y period prevalence, point prevalence, prevalence of
      chronic pain, and prevalence of persistent chronic pain). In those with
      persistent chronic pain, women tended to report higher severity scores.
      DISCUSSION: The present study shows that women have higher prevalence rates of
      musculoskeletal pain in most anatomic pain sites, no matter the duration of
      musculoskeletal pain. Future research should focus on explaining these sex
      differences with the ultimate goal to develop better prevention and management
      strategies for musculoskeletal pain in both men and women.

PMID- 16988569
TI  - Evidence that trait-anxiety and trait-depression differentially moderate cortical
      processing of pain.
AB  - OBJECTIVES: The purpose of this study was to examine the influence of neuroticism
      (N) and its different subfacets anxiety (N-anx) and depression (N-dep) on
      cortical pain processing expressed as event-related potentials (ERPs). METHODS:
      Seventy-five healthy participants received electrical pain stimuli under
      condition of simultaneous electroencephalogram registration. Multiple regression
      analyses were conducted to study the amount of pain-ERP variance. ERP variance
      was explained by N and its subfacets. RESULTS: N moderated the way pain was
      processed cortically. Higher levels of N were associated with higher pain-ERP
      amplitudes. Within this association, differential subfacet effects were observed:
      N-anx reduced, whereas N-dep augmented pain-ERP amplitudes. DISCUSSION: A
      personality trait reflecting bias toward negative emotions may moderate the way
      pain is processed cortically, with directionally different effects depending on
      whether the trait is expressed predominantly in the realm of anxiety or
      depression.

PMID- 16988570
TI  - Pain-related catastrophizing in healthy women is associated with greater temporal
      summation of and reduced habituation to thermal pain.
AB  - OBJECTIVE: Pain-related coping strategies, especially catastrophizing, play an
      influential role in shaping pain responses. However, although numerous studies
      have examined the impact of catastrophizing on chronic pain outcomes, relatively
      few have evaluated relationships between individual differences in pain-related
      catastrophizing and pain perception, with most of those studies examining only
      pain threshold or pain tolerance. We assessed, for the first time,
      catastrophizing's association with the magnitude of temporal summation of pain, a
      primary marker for central nervous system sensitizability. METHODS: Thirty-eight
      healthy young women underwent standardized experimental pain testing, followed by
      administration of a brief questionnaire that assessed catastrophizing cognitions
      during the pain-testing session. RESULTS: Higher levels of pain-related
      catastrophizing were related to higher suprathreshold pain ratings and greater
      temporal summation of thermal pain, suggesting that catastrophizing may play a
      facilitatory role in the processing of pain-related information, though the
      specific pathways underlying this facilitation are not clear. CONCLUSIONS: These
      preliminary findings highlight the importance of coping in shaping individuals'
      responses to noxious stimuli, and suggest that interventions that decrease pain
      catastrophizing may reduce the burden of acute and chronic pain.

PMID- 16988571
TI  - Why do women have back pain more than men? A representative prevalence study in
      the federal republic of Germany.
AB  - OBJECTIVES: In comparison with men, women have a healthier lifestyle, are more
      rarely overweight, have less stressful occupations, or are not employed outside
      the home. The "gender pain bias" is the fact that women nevertheless have a
      higher prevalence of back pain. This paper looks at the possible underlying
      reasons for this as yet unexplained gender difference, using Stokols'
      socioecological health model as a basis. METHODS: The first National Health
      Survey for the Federal Republic of Germany was carried out from October 1997 to
      March 1999. It comprised a representative total sample of 5315 persons between
      the ages of 20 and 64. The participants took part in a medical examination and
      answered a self-report form. chi test and logistic regression analyses were used
      to investigate correlations between self-reported low back pain and gender
      specific biopsychobehavioral and sociophysical environmental factors. RESULTS:
      Seven-day back pain prevalence in the Federal Republic of Germany is 32% for men
      and 40% for women. Prevalences are significantly higher for overweight subjects,
      persons with a marked somatization tendency or a low level of social support,
      physically inactive individuals, smokers, elderly subjects, the nonemployed,
      "blue collar workers" and lower socioeconomic groups. From a multivariate
      perspective, however, none of these factors reduces (and hence sufficiently
      explains) the gender difference. Factoring in the gender-specific somatization
      tendency reduces the odds ratios of women versus men from 1.42 to 1.23.
      DISCUSSION: In view of the gender difference in pain prevalence, which remains
      stable despite a multivariate perspective, there is clearly a need for more
      research into the reasons underlying the gender difference. We believe that
      future studies should look at rarely investigated constructs such as "sex role
      expectancies," "anxiety," "ethnicity," and "family history" and take anatomic
      differences in muscle strength into account.

PMID- 16988572
TI  - Author's response"Opioid tolerance often ignored".

PMID- 16988574
TI  - Current status of digital mammography for screening and diagnosis of breast
      cancer.
AB  - PURPOSE OF REVIEW: Digital mammography is becoming the preferred technique for
      investigation of the breast. It is important, therefore, to analyze not only the
      accuracy of this technique in the screening and the diagnostic environment but
      also to evaluate its strengths and limits. In addition, communication with other
      specialists inside and outside the hospital is essential. RECENT FINDINGS: Recent
      publications of large clinical trials have shown that digital mammography is as
      accurate as film-screen mammography in a screening setting. Technical protocols
      for acceptance testing of these modalities are emerging but they are not yet
      complete. The literature shows that reading on soft copy may be preferred to hard
      copy. The high cost is still an important limiting factor in the easy
      introduction of full-field digital mammography in a hospital. SUMMARY: Digital
      mammography is becoming the method of choice in the detection and
      characterization of breast cancer. Today, physical and technical protocols as
      well as large clinical trials are assessing the performance of this technology. A
      lot of work remains in the optimization of the different parts of the imaging
      chain: exposure setting, acceptability of detectors, dedicated post processing,
      viewing conditions and computer-aided detection. In parallel with these
      developments, newer digital technologies are being explored (tomosynthesis).

PMID- 16988575
TI  - New trends in radiotherapy for breast cancer.
AB  - PURPOSE OF REVIEW: New radiotherapy techniques are under development to improve
      tumor control and to decrease the long-term side effects of breast cancer. These
      include accelerated partial breast irradiation, intensity modulated and image
      guided radiotherapy. RECENT FINDINGS: Follow-up data of multicatheter
      brachytherapy accelerated partial breast irradiation and intraoperative electron
      beam radiotherapy confirm excellent 5-year local control rates in well selected
      patients. Early side effects seem to be improved, but recent data show increasing
      skin toxicity in multicatheter and intracavitary balloon brachytherapy.
      Intraoperative radiotherapy, proton beam partial breast irradiation, intensity
      modulated and image guided radiotherapy improve dose homogeneity and decrease
      normal tissue complication probability. For breast-only treatment, two tangential
      fields with different segments provide an attractive and feasible alternative to
      the conventional technique. The proposed intensity modulated radiotherapy
      techniques for comprehensive locoregional radiotherapy, however, result in
      increased doses to the contralateral lung and breast. SUMMARY: Input from long
      term clinical data on new radiotherapy techniques is needed. Consensus on target
      volume contouring and dose volume constraints for nontarget tissue has not yet
      been reached. Further research on skin toxicity with multicatheter or
      intracavitary brachytherapy is needed to improve the results.

PMID- 16988576
TI  - Inflammatory breast cancer: current understanding.
AB  - PURPOSE OF REVIEW: Inflammatory breast cancer is a highly aggressive variant of
      locally advanced breast cancer that carries a significantly worse prognosis. The
      purpose of this review is to highlight recent advances in the molecular modus
      operandi of this particular form of breast cancer. RECENT FINDINGS: Studies on
      tumor cell emboli, E-cadherin, chemokine receptors, steroid hormone receptor,
      angiogenesis, lymphangiogenesis and gene expression all suggest significant
      differences with noninflammatory breast cancer and are clearly in line with a
      different pathogenesis of the condition. SUMMARY: This comprehensive review will
      hopefully allow for better treatment modalities with targeted approaches as
      suggested by the early data on anti-vascular endothelial growth factor treatment
      in inflammatory breast cancer.

PMID- 16988577
TI  - Optimal sequence of hormonotherapy in advanced breast cancer.
AB  - PURPOSE OF REVIEW: Several active, well tolerated hormonal agents have become
      available in recent years for the treatment of patients with advanced, hormone
      receptor-positive breast cancer. When used in an appropriate sequential strategy,
      hormonal therapies offer the opportunity of prolonging disease control and
      maintaining quality of life. The widening use of aromatase inhibitors in the
      adjuvant setting, however, means that traditional sequential cascades must be
      revised. The review describes the most relevant evidence that can contribute to
      the optimal positioning of each agent in the sequence. RECENT FINDINGS: Most
      recent phase II and III trials of hormonal therapy in advanced breast cancer have
      examined the role of exemestane, letrozole, anastrozole, and fulvestrant in
      postmenopausal women. SUMMARY: Partial non-cross resistance between nonsteroidal
      (letrozole and anastrozole) and steroidal (exemestane) aromatase inhibitors may
      allow treatment with exemestane after a nonsteroidal aromatase inhibitor and vice
      versa. The estrogen receptor downregulator fulvestrant is also an option after
      treatment with aromatase inhibitors. The role of the progestin megestrol acetate
      and, paradoxically, of tamoxifen in the sequential strategy for advanced breast
      cancer is less well studied.

PMID- 16988578
TI  - Novel tyrosine kinase inhibitors in chronic myelogenous leukemia.
AB  - PURPOSE OF REVIEW: The successful introduction of the tyrosine kinase inhibitors
      has initiated a new era in the management of chronic myeloid leukemia. RECENT
      FINDINGS: Imatinib therapy has significantly improved prognosis of chronic
      myeloid leukemia. A minority of patients with chronic-phase disease (4% annually)
      and considerably more in advanced stages develop resistance. This is attributed,
      in 40-50% of cases, to the development of BCR-ABL (breakpoint cluster
      region/Abelson oncogene) tyrosine kinase domain mutations that impair imatinib
      binding. This has led to the development of more potent novel tyrosine kinase
      inhibitors that can overcome both BCR-ABL-dependent and BCR-ABL-independent
      mechanisms of resistance. Preliminary results of phase I and II trials with
      dasatinib and nilotinib have provided promising data that may reduce disease
      progression and potentially prevent acquired resistance to the tyrosine kinase
      inhibitors. SUMMARY: Novel tyrosine kinase inhibitors with more potent and
      selective Bcr-Abl inhibition and with multitargeted inhibition of Bcr-Abl and Src
      family kinases are promising and may further improve prognosis in chronic myeloid
      leukemia.

PMID- 16988579
TI  - Clofarabine and nelarabine: two new purine nucleoside analogs.
AB  - PURPOSE OF REVIEW: Both clofarabine and nelarabine recently received an
      accelerated approval by the US Food and Drug Administration for use in refractory
      or relapsed pediatric acute lymphoblastic leukemia and in refractory-relapsed T
      cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Both drugs
      have been studied for their metabolism and mechanisms of action in preclinical
      investigations and for their efficacy in clinical trials. This review will
      summarize these investigations and will suggest future plans with these
      nucleoside analogs. RECENT FINDINGS: Clofarabine and nelarabine were designed
      based on preclinical and clinical findings with other nucleoside analogs or
      normal deoxynucleotides such as dGTP. Studies in cell lines have demonstrated
      that triphosphate is the active metabolite for both these purine nucleoside
      analogs. Pharmacokinetic and pharmacodynamic investigations during clinical
      trials have verified the importance of triphosphate levels in achieving clinical
      responses. Several phase I and II clinical explorations have suggested the
      utility of clofarabine in acute leukemias and nelarabine in T-cell diseases. Dose
      limiting toxicities were nonhematologic: hepatotoxicity for clofarabine and
      neurotoxicity for nelarabine. SUMMARY: Clofarabine is the first deoxyadenosine
      analog that shows promise in adult and pediatric acute leukemias without untoward
      toxicity. Nelarabine, as expected from its design, is a drug that may be directed
      to T-cell diseases.

PMID- 16988580
TI  - Pralatrexate: an emerging new agent with activity in T-cell lymphomas.
AB  - PURPOSE OF REVIEW: T-cell lymphomas (TCL) represent a particularly poor prognosis
      subgroup of lymphomas. The goal of this review is to provide emerging information
      on one agent demonstrating activity in these challenging diseases. Pralatrexate
      is a novel antifolate designed to have high affinity for the reduced folate
      carrier type 1 (RFC-1). Preclinical and clinical studies have demonstrated that
      pralatrexate has significant activity against TCL. RECENT FINDINGS: The high
      affinity of pralatrexate for RFC-1 significantly improves its internalization
      into cells. Preclinical studies in models of B-cell lymphomas and TCL have
      demonstrated that pralatrexate demonstrates activity superior to traditional
      antifolates. Phase I studies have shown the dose-limiting toxicity to be
      stomatitis, which can be abrogated with folic acid and vitamin B12
      supplementation. Early phase studies have shown marked activity across a diverse
      panoply of TCL. SUMMARY: Pralatrexate is an antifolate designed to be
      internalized more rapidly than other traditional antifolates. Preclinical studies
      have demonstrated its superiority to methotrexate, and early phase I and II
      studies have shown marked activity across many poor-risk subtypes of TCL. Future
      studies are directed towards understanding the pharmacokinetic features of the
      drug, and expanding the population of patients with TCL and B-cell lymphomas.

PMID- 16988581
TI  - Beyond single-agent bortezomib: combination regimens in relapsed multiple
      myeloma.
AB  - PURPOSE OF REVIEW: Bortezomib-based combinations are being investigated in
      relapsed or refractory multiple myeloma with the aim of improving outcomes. This
      review presents recent data from clinical trials of these combinations and
      discusses their implications. RECENT FINDINGS: Preclinical findings indicating
      additive or synergistic activity of bortezomib plus conventional and novel agents
      for multiple myeloma appear to be supported by clinical studies of bortezomib
      based combinations. Bortezomib combined with a broad set of active agents results
      in enhanced response rates, including high complete response rates. Encouraging
      responses to bortezomib and its combinations are also seen in elderly patients,
      patients with adverse prognostic factors such as refractory disease and increased
      beta2-microglobulin, patients with cytogenetic abnormalities such as chromosome
      13 deletion, advanced bone disease, extramedullary involvement, and patients with
      renal impairment, including patients with renal failure requiring dialysis.
      Toxicities are predictable and manageable and comparable to those seen with
      bortezomib monotherapy. SUMMARY: Bortezomib-based combinations show promising
      activity in relapsed or refractory multiple myeloma, including reversal of
      chemoresistance to previously used agents. As high complete and overall response
      rates translate into longer survival, bortezomib-based combinations appear likely
      to have a significant impact on the multiple myeloma treatment algorithm and on
      the course of the disease itself.

PMID- 16988582
TI  - Epidermal growth factor receptor pathway targeted therapy in patients with
      aerodigestive malignancies.
AB  - PURPOSE OF REVIEW: The present review will describe progress in the utilization
      of epidermal growth factor receptor (EGFR) inhibitors in the treatment of
      nonsmall-cell lung cancer and the treatment of squamous cell carcinoma of the
      head and neck. Recent findings regarding clinical activity as well as markers
      associated with sensitivity to these agents will be reviewed. RECENT FINDINGS:
      The EGFR pathway plays a crucial role in human carcinogenesis by contributing to
      relevant processes in tumor development and progression, including cell
      proliferation, differentiation, regulation of apoptotic cell death, metastatic
      potential, and blood vessel formation. Anti-EGFR agents include monoclonal
      antibodies that target the EGFR extracellular receptor domain, and small molecule
      tyrosine kinase inhibitors that target the EGFR intracellular domain. Both
      strategies have demonstrated encouraging results as monotherapies and in
      combination with chemotherapy and radiotherapy in areodigestive malignancies.
      SUMMARY: These dramatic successes have led to further clinical studies of EGFR
      targeted therapy in aerodigestive malignancies, making a significant impact on
      the clinical care of patients with nonsmall-cell lung cancer and squamous cell
      carcinoma of the head and neck.

PMID- 16988583
TI  - Sorafenib.
AB  - PURPOSE OF REVIEW: Sorafenib is an oral, multikinase inhibitor that was recently
      approved for use in metastatic renal cancer. It is currently undergoing
      investigation in locally advanced renal cancer and in other tumor types. RECENT
      FINDINGS: Sorafenib was initially developed as an inhibitor of Raf kinase;
      however, it has broad spectrum activity against multiple tyrosine kinases,
      including angiogenic factors VEGFR and PDGFR. Common toxicities experienced with
      sorafenib include hypertension, hand-foot syndrome, rash, diarrhea and fatigue.
      Early clinical trials suggested that sorafenib acts as a cytostatic agent, as
      many patients experienced prolonged disease stabilization but insufficient tumor
      shrinkage to meet RECIST criteria for response. To assess whether sorafenib's
      growth inhibition translated into a clinical benefit, a phase II randomized
      discontinuation trial was designed. This trial demonstrated that sorafenib
      increased progression-free survival in patients with metastatic renal cell
      cancer; the phase II data were confirmed in a large international phase III
      trial. SUMMARY: In this review, we will discuss the clinical development of
      sorafenib and its role in the treatment of renal cancer. Additionally, we will
      highlight critical methods of clinical trial design and biomarker development
      that contribute to the development of sorafenib.

PMID- 16988585
TI  - Molecular changes in brain tumors: prognostic and therapeutic impact.
AB  - PURPOSE OF REVIEW: This review focuses on recent advances in the molecular
      biology of the main primary brain tumors (gliomas, medulloblastomas, and
      ependymomas), with particular emphasis on prognostic markers and potential
      therapeutic targets. RECENT FINDINGS: Current biologic markers are useful for
      predicting prognosis (e.g. 1p/19q codeletion in grade 2 and 3 gliomas, nuclear
      beta-catenin expression in medulloblastoma) or response to the treatment (e.g.
      the methyl guanyl methyl transferase promoter methylation status). Recent gene
      profiling studies have identified specific molecular signatures that permit a
      molecular classification and that also provide new, potentially useful prognostic
      markers. The studies have also shown a striking parallel between central nervous
      system ontogenesis and the oncogenesis of brain tumors. By elucidating the
      underlying activated molecular pathways, these approaches provide the basis for a
      biologic therapy to target the critically activated pathways. SUMMARY: Important
      advances have been made in the biologic understanding, molecular
      subclassification, and identification of prognostic markers in brain tumors,
      thereby improving the current classifications. Such data provide a rational basis
      for current and future targeted biologically based strategies.

PMID- 16988586
TI  - Recent advances in immunotherapy for human glioma.
AB  - PURPOSE OF REVIEW: The present review focuses on recent progress in tumour
      immunology and immunotherapeutic trials in malignant gliomas. RECENT FINDINGS:
      Major advances have been made in the understanding of antitumour immunity in
      patients with glioma. Patients with glioblastoma can spontaneously develop
      antitumour activity with activated CD8+ T cells. Infiltration of myeloid
      suppressor cells into tumours and increased regulatory T-cell fraction appear to
      play a critical role in tumour tolerance, however. T-regulatory removal
      suppresses CD4+ T-cell proliferative defects and can induce tumour rejection in a
      murine model. Clinical trials using active immunotherapy with dendritic cells
      loaded with tumour-eluted peptides or tumour lysate have successfully induced
      antitumour cytotoxicity and some radiologic responses. Other promising approaches
      targeting the mechanisms of tolerance that could be referred to as 'corrective
      immunotherapy' are currently on going. SUMMARY: Improvements in clinical methods
      and large randomized trials are now needed to prove the usefulness of cancer
      vaccines. Indeed, comprehensive analysis of tumour immunology and new
      immunization protocols suggest that immunotherapy can become an efficacious
      treatment in the near future. Combination with radiotherapy or chemotherapy
      should be investigated.

PMID- 16988587
TI  - Treatment of central nervous system metastases: parenchymal, epidural, and
      leptomeningeal.
AB  - PURPOSE OF REVIEW: With prolonged survival from systemic therapies in the
      adjuvant and salvage setting, and because these agents cannot cross the intact
      blood-brain barrier, central nervous system metastases are becoming a therapeutic
      challenge in oncology. RECENT FINDINGS: Recent therapeutic achievements include
      an extended use of surgery and radiosurgery. Although each of these treatment
      modalities has its own indications, in patients eligible for both treatments the
      upfront comparison of these two techniques has not been performed yet. Systemic
      chemotherapies and biotherapies may be effective in the management of central
      nervous system metastases as they may act on both neurologic and extra-central
      nervous system lesions. In the treatment of epidural metastases, a surgical
      procedure providing immediate direct circumferential decompression of the spinal
      cord followed by local irradiation has been demonstrated in a prospective
      randomized trial. The management of leptomeningeal metastases remains
      controversial and of limited efficacy especially in chemoresistant tumours and
      still relies on the combination of chemotherapy (intrathecal and intravenous) and
      focal radiotherapy. SUMMARY: Aggressive treatments in patients with early
      diagnosis and in whom central nervous system metastases are the life-threatening
      location may provide a substantial increase in survival and favourably affect
      quality of life.

PMID- 16988588
TI  - Glioma in the elderly.
AB  - PURPOSE OF REVIEW: This review updates available data on the management of
      gliomas in the elderly. RECENT FINDINGS: Prospective randomized studies have
      recently established the benefit of radiotherapy and the validity of an
      accelerated course of irradiation in older patients with malignant gliomas.
      SUMMARY: The incidence of gliomas is increasing in the elderly population.
      Unfortunately, increasing age is one of the most consistent negative prognostic
      factors in gliomas and the optimal management of this population remains
      unsettled since patients aged 65 years or more are usually excluded from clinical
      trials. The previous nihilistic approach is progressively changing towards more
      active strategies with recent evidence that older patients (70-80 years) may
      benefit from surgery, radiotherapy, or chemotherapy. Initial performance status,
      quality of life, and concomitant pathologies are important factors to consider
      before treatment onset. In the future, it will be necessary to design specific
      schedules of treatment in this population.

PMID- 16988589
TI  - Treatment of malignant haematological diseases: from maximally tolerated to
      minimally required?

PMID- 16988590
TI  - The changing scene of adult acute lymphoblastic leukemia.
AB  - PURPOSE OF REVIEW: The review focuses on the most recent advances in the
      diagnostic and prognostic work-up of adult acute lymphoblastic leukemia (ALL) and
      its implications in the clinical management of the disease. RECENT FINDINGS: ALL
      can be identified on the basis of morphologic, cytochemical and immunophenotypic
      criteria; modern management of ALL is also based on cytogenetic and genetic
      evaluations. New technologies, such as gene expression profile analysis, may
      allow us to further unravel the intrinsic biology of the disease, to improve
      diagnostic and prognostic stratification, and to design innovative therapeutic
      strategies. In potentially all cases, specific markers of the disease can be
      found and utilized together with the rearrangement of immunoglobulin and T-cell
      receptor genes to monitor minimal residual disease during clinical follow-up.
      These biologically-defined subgroups of patients may have a different clinical
      course, response to treatment and variable prognosis. SUMMARY: Recent biologic
      advancements are progressively realising the possibility of designing targeted
      and individualized therapeutic strategies according to the more refined,
      molecularly defined features of leukemic cells and the presence or absence of
      residual disease in adult ALL.

PMID- 16988591
TI  - Chemotherapy and radiotherapy in Hodgkin's lymphoma: joining in or splitting up?
AB  - PURPOSE OF REVIEW: Radiotherapy is very effective in local control of Hodgkin's
      lymphoma. Unfortunately, long-term survivors exhibit an excess of life
      threatening radiation-related late side effects. Consequently, there have been
      calls to cease the use of radiation in the primary treatment of Hodgkin's
      lymphoma, although there is also support for the judicious use of combined
      modality treatment. RECENT FINDINGS: Most patients treated for Hodgkin's lymphoma
      are being cured with modern approaches. Recent publications confirm the superior
      efficacy of combined modality treatment over chemotherapy alone, but the initial
      gain in cure rate may be outweighed by late deaths due to various treatment
      related diseases. Many patients may already be cured by chemotherapy alone.
      Classical risk factors can be used to distinguish favourable and unfavourable
      subgroups of patients with Hodgkin's lymphoma, but these risk factors cannot
      predict outcome in individual cases. A simple test to predict the likelihood of
      cure in individual patients would be of great benefit. Fluoro-deoxyglucose-PET
      scan investigation holds this promise. SUMMARY: The present review deals with the
      role of radiation therapy in the treatment of Hodgkin's lymphoma.

PMID- 16988592
TI  - Differences between the different conditioning regimens for allogeneic stem cell
      transplantation.
AB  - PURPOSE OF REVIEW: The aim of this article is to compare the differences in
      efficacy and toxicity between the various conditioning regimens for allogeneic
      stem cell transplantation. RECENT FINDINGS: Several studies, all retrospective,
      that compare the impact of various different conditioning regimens amongst each
      other are presented. Reduced intensity conditioning apparently lowered transplant
      related mortality in patients with minimal residual disease who were at high risk
      for treatment-related mortality. In contrast, patients with active disease could
      only be salvaged when a myeloablative conditioning regimen was used. By
      consequence, it was concluded that patients without contraindications for a
      myeloablative conditioning regimen should not receive reduced regimens outside a
      prospective randomized trial. SUMMARY: Despite high expectations, non
      myeloablative conditioning regimens and regimens that have been reduced in
      intensity did not prove to be superior in survival when the outcomes were
      compared with those obtained with conventional myeloablative conditioning.
      Randomized prospective studies are needed to explore the appropriate niche for
      the various different regimens.

PMID- 16988593
TI  - Bibliography. Current world literature.

PMID- 16988594
TI  - Effect of sublingual application of cannabinoids on intraocular pressure: a pilot
      study.
AB  - PURPOSE: The purpose of this study was to assess the effect on intraocular
      pressure (IOP) and the safety and tolerability of oromucosal administration of a
      low dose of delta-9-tetrahydrocannabinol (Delta-9-THC) and cannabidiol (CBD).
      PATIENTS AND METHODS: A randomized, double-masked, placebo-controlled, 4 way
      crossover study was conducted at a single center, using cannabis-based medicinal
      extract of Delta-9-THC and CBD. Six patients with ocular hypertension or early
      primary open angle glaucoma received a single sublingual dose at 8 AM of 5 mg
      Delta-9-THC, 20 mg CBD, 40 mg CBD, or placebo. Main outcome measure was IOP.
      Secondary outcomes included visual acuity, vital signs, and psychotropic effects.
      RESULTS: Two hours after sublingual administration of 5 mg Delta-9-THC, the IOP
      was significantly lower than after placebo (23.5 mm Hg vs. 27.3 mm Hg, P=0.026).
      The IOP returned to baseline level after the 4-hour IOP measurement. CBD
      administration did not reduce the IOP at any time. However, the higher dose of
      CBD (40 mg) produced a transient elevation of IOP at 4 hours after
      administration, from 23.2 to 25.9 mm Hg (P=0.028). Vital signs and visual acuity
      were not significantly changed. One patient experienced a transient and mild
      paniclike reaction after Delta-9-THC administration. CONCLUSIONS: A single 5 mg
      sublingual dose of Delta-9-THC reduced the IOP temporarily and was well tolerated
      by most patients. Sublingual administration of 20 mg CBD did not reduce IOP,
      whereas 40 mg CBD produced a transient increase IOP rise.

PMID- 16988595
TI  - Effect of latanoprost on the diurnal variations in the intraocular and ocular
      perfusion pressure in normal tension glaucoma.
AB  - PURPOSE: To evaluate the effects of latanoprost on the diurnal variations in the
      intraocular pressure (IOP) combined with the ocular perfusion pressure (OPP) in
      patients with normal tension glaucoma (NTG). PATIENTS AND METHODS: Twenty-two
      eyes from 22 patients with NTG were used for the study. The diurnal variations in
      the IOP and blood pressure (BP) were measured every 3 hours without therapy, and
      then the patients were treated with latanoprost (0.005%) once daily for more than
      12 weeks. The diurnal variations in the IOP and BP under medication were again
      measured every 6 hours. The diurnal variation of IOP for 24 hours, mean diurnal
      IOP, maximum IOP, minimum IOP, range of variation in IOP, OPP, and BP were
      compared between the baseline and after treatment by means of a paired t test.
      RESULTS: At 3 months after the start of the latanoprost treatment regimen, the
      IOP showed a statistically significant decrease at every assessed time point over
      24 hours (P<0.001). Latanoprost significantly reduced the mean diurnal IOP,
      maximum IOP, minimum IOP, and mean range of variation in the IOP values from
      baseline (P<0.001, <0.001, <0.001, and 0.009, respectively). OPP after treatment
      showed no significant difference at any assessed time points from the baseline
      (P>0.1). Latanoprost did not significantly alter the mean diurnal OPP (P>0.1),
      and BP (P>0.5) from the baseline. CONCLUSIONS: Latanoprost was thus found to
      significantly reduce IOP over 24 hours, whereas it does not affect OPP and BP in
      NTG patients. Therefore, it may be a useful medication for NTG.

PMID- 16988596
TI  - Distribution of optineurin sequence variations in an ethnically diverse
      population of low-tension glaucoma patients from the United States.
AB  - PURPOSE: Previous studies have suggested that Optineurin (OPTN) sequence variants
      contribute to low-tension glaucoma (LTG) in ethnically homogeneous populations.
      The purpose of this study is to evaluate the prevalence of OPTN sequence variants
      in an ethnically diverse population of LTG patients from the United States, and
      to describe the phenotype of patients with OPTN sequence variants preferentially
      found in LTG patients. METHODS: Genomic DNA purified from 67 LTG patients was
      screened for DNA sequence variants located in the exons and flanking introns of
      the OPTN gene using high-performance liquid chromatography analysis and direct
      genomic DNA sequencing. Eighty-six primary open-angle glaucoma probands and 100
      control patients were also analyzed. RESULTS: Nine OPTN DNA sequence variants
      were identified in this patient population including the 2 previously identified
      heterozygous nonsynonymous single-nucleotide polymorphisms in exons 4 and 5. Four
      LTG patients with severe disease and positive family history of glaucoma, were
      found to have DNA sequence changes not found in primary open-angle glaucoma
      probands or control individuals including the previously reported E50K variation.
      CONCLUSIONS: The results of this study support the rare association of OPTN
      sequence variants with familial forms of LTG. The E50K mutation seems to be
      associated with a severe form of LTG, and although rare, the identification of
      this sequence variant in patients at risk may help direct appropriate therapy.

PMID- 16988597
TI  - Evaluation of the influence of corneal biomechanical properties on intraocular
      pressure measurements using the ocular response analyzer.
AB  - PURPOSE: The Ocular Response Analyzer (ORA) proposes to measure corneal
      biomechanical properties in vivo by monitoring and analyzing the corneal behavior
      when this structure is submitted to a force induced by an air jet. The purpose of
      this study was to evaluate the relationship between corneal biomechanical
      properties and corneal-compensated intraocular pressure (IOPCC) measurements as
      obtained by the ORA and Goldmann applanation tonometry (GAT) measurements.
      DESIGN: Observational clinical study. METHODS: The study included 153 eyes of 78
      subjects. All subjects underwent IOP evaluation with the ORA and GAT, and also
      measurements of central corneal thickness (CCT), corneal curvature, and axial
      length. Univariable and multivariable regression analysis were used to evaluate
      the associations between IOP (as measured with GAT and ORA) and CCT, corneal
      curvature, axial length, and age. Bland and Altman plots were used to evaluate
      the agreement between IOP measurements obtained by GAT and ORA. RESULTS: GAT IOP
      measurements were significantly associated with CCT (P=0.001) and corneal
      curvature (P<0.001), whereas ORA IOPCC measurements were not associated with any
      of the ocular variables. The difference between GAT and IOPCC measurements was
      significantly influenced by corneal thickness. Patients with thicker corneas
      tended to have higher GAT IOP measurements compared with IOPCC, whereas in
      patients with thin corneas, GAT IOP measurements tended to be lower than IOPCC.
      CONCLUSIONS: ORA IOPCC measurements seem to provide an estimate of IOP that is
      less influenced by corneal properties than those provided by GAT.

PMID- 16988598
TI  - Long ciliary processes with no ciliary sulcus and appositional angle closure
      assessed by ultrasound biomicroscopy.
AB  - PURPOSE: Nonpupil block mechanisms and appositional angle closure after laser
      iridotomy (LI) have been reported as common findings in Asians. We evaluated the
      presence of these findings in a cohort of Brazilian patients using ultrasound
      biomicroscopy (UBM). METHODS: This observational case-control study included 22
      open angle eyes and 31 eyes with occludable angles on gonioscopy (defined by 2
      examiners). UBM radial scans through a typical ciliary process were obtained in
      both light and dark conditions, at 6 and 12-o'clock positions. Long ciliary
      processes with no ciliary sulcus were determined on the basis of a reference line
      drawn perpendicular to the iris plane passing through a point located 750 mum
      from scleral spur. Trabecular ciliary processes distance was measured on 6
      o'clock UBM images. RESULTS: After LI, 52% of occludable angle eyes had
      appositional angle closure in both 6 and 12-o'clock UBM images. We also observed
      this finding in 14% and 23% of the control eyes (in 6 and 12-o'clock UBM images,
      respectively). A long ciliary process with no ciliary sulcus was observed in 61%
      of occludable angle eyes, and also in 32% of control eyes (6-o'clock UBM images).
      Control eyes had longer trabecular ciliary processes distance than occludable
      angle eyes (P<0.001). CONCLUSIONS: The UBM finding of long ciliary processes
      associated with the absence of ciliary sulcus is not necessarily related to an
      anterior positioning of the ciliary processes. Whether UBM appositional angle
      closure after LI is associated with further angle closure process and/or poor
      intra-ocular pressure control remains to be evaluated.

PMID- 16988599
TI  - Comparison between newly developed scanning peripheral anterior chamber depth
      analyzer and conventional methods of evaluating anterior chamber configuration.
AB  - PURPOSE: To compare the newly developed scanning peripheral anterior chamber
      depth analyzer (SPAC) with the Van Herick technique, the Shaffer grading system,
      and ultrasound biomicroscopy (UBM), in terms of accuracy of measurement of
      peripheral anterior chamber depth (ACD). METHODS: The subjects were well
      controlled glaucoma patients who were being treated at the University of
      Yamanashi Hospital. Ten eyes from each of the 4 groups classified as Shaffer
      grades 1 to 4 were evaluated by SPAC, the Van Herick technique, and UBM. All
      measurements were performed independently on the temporal side in a masked
      fashion. SPAC evaluated ACD consecutively from the pupil center to the limbus at
      0.4 mm intervals. UBM measurements were carried out at a depth of 500 mum (angle
      opening distance 500) from the scleral spur. A dummy eye was used for evaluating
      SPAC measurement accuracy. RESULTS: The results of SPAC measurement were well
      correlated with those of the Van Herick technique and the Shaffer grading system.
      The SPAC measurement results were also significantly correlated with angle
      opening distance 500. The correlation coefficients at distances of 2, 4, 4.8, and
      5.6 mm from the pupil center were r=0.68, 0.69, 0.69, and 0.61, respectively, and
      the P values of all the correlations were less than 0.0001. Study of the dummy
      eye revealed that SPAC has high accuracy for measuring ACD and that the
      coefficient variances were less than 1.0% at all measured points. CONCLUSIONS:
      The results of SPAC measurement correlate well with those of the conventional
      methods.

PMID- 16988600
TI  - Development of a fully automated peripheral anterior chamber depth analyzer and
      evaluation of its accuracy.
AB  - PURPOSE: The aim of this study was to improve the scanning peripheral anterior
      chamber depth analyzer (SPAC) for measuring anterior chamber depth (ACD),
      differentiating eyes with shallow anterior chamber, and automatically
      categorizing eyes into subgroups based on the ACD values. We also investigated
      its accuracy for measuring anterior ocular biometry. MATERIALS AND METHODS: The
      improved SPAC system was equipped with an auto-focusing system for measuring ACD
      from the optical axis to the limbus without contacting the ocular surface, in
      addition to an auto-measuring system for determining central corneal thickness
      (CCT) and corneal radius of curvature (CRC). This system was also equipped with
      an auto-diagnosing program for differentiating eyes with narrow angle and an auto
      classifying program for categorizing eyes into 12 subgroups according to the ACD
      values. A dummy eye was used for investigating the measurement accuracy and
      reproducibility of CCT, CRC, and ACD. Measurement duration and clinical
      availability were investigated using healthy subjects and glaucoma patients.
      RESULTS: The SPAC-measured CCT, CRC, and ACD values were very similar to the
      theoretical values obtained from the dummy eye and their coefficients of
      variation were less than 1%. This system completed ACD measurement in 15.6+/-1.0
      seconds and the mean coefficient of variation of ACD was 8.8+/-2.3%. The improved
      SPAC system successfully differentiated eyes with narrow angle from those with
      wide open angle. CONCLUSIONS: The improved SPAC system can measure ACD easily
      with good accuracy and reproducibility, and is considered to be suitable for
      evaluating ACD in routine examinations and screening eyes with narrow angle.

PMID- 16988601
TI  - High prevalence of plateau iris configuration in family members of patients with
      plateau iris syndrome.
AB  - PURPOSE: The purpose of the study was to ascertain the prevalence of plateau iris
      syndrome in the first-degree relatives of those patients affected with plateau
      iris syndrome. METHODS: All patients seen with plateau iris syndrome over a 5
      year period were identified. These patients were approached for participation and
      first-degree family members above 18 years of age were screened. All people
      identified with plateau iris configuration underwent ultrasound biomicroscopy to
      document and confirm the angle configuration and subsequent gonioscopy after
      laser iridotomies. RESULTS: Sixteen patients were identified; 3 refused to
      participate, 2 were unable to be contacted, and 1 withdrew after initially
      consenting to participate. In this case, the patient agreed to participate, but
      all her living first-degree family members refused to be screened. Among the 10
      patients whose living first-degree relatives were screened, we found 5 families
      with at least 1 additional first-degree family member having plateau iris
      syndrome. CONCLUSIONS: Some families have more than 1 member with plateau iris
      syndrome. The pattern of inheritance resembles an autosomal dominant pattern with
      incomplete penetrance.

PMID- 16988602
TI  - Learning effect of short-wavelength automated perimetry in patients with ocular
      hypertension.
AB  - AIM: To evaluate the learning effect of short-wavelength automated perimetry
      (SWAP) on a group of patients with ocular hypertension experienced with standard
      automated perimetry (SAP). METHODS: Thirty patients with ocular hypertension
      underwent 5 full-threshold SWAP tests at intervals of 7+/-2 days. The parameters
      investigated to detect a learning effect were duration, the perimetric indices,
      and the number of points with a P of <5% and 1% in the total and pattern
      deviation maps. Differences in learning effect were also evaluated by comparing
      the sensitivities of central, paracentral, and peripheral areas, hemifields and
      quadrants. RESULTS: Learning effects were demonstrated for mean defect (P<0.0001,
      analysis of variance), duration (P=0.0001), the number of points with P<5% in the
      pattern deviation map (P=0.003), and short fluctuations (P=0.03). The effect was
      greater in the peripheral than in central areas (P=0.04). Mean defect was the
      most sensitive parameter, for which the learning effect was statistically
      significant between the first and the fifth test. CONCLUSIONS: The results of
      this study demonstrate a significant learning effect at full-threshold SWAP. This
      may limit the efficacy of this kind of perimetry in detecting early glaucoma, and
      should therefore be carefully considered when creating normative databases for
      new SWAP strategies.

PMID- 16988603
TI  - A comparison of algorithms for calculating glaucoma change probability confidence
      intervals.
AB  - PURPOSE: To evaluate the ability to detect change in standard automated perimetry
      data using 4 different methods for calculating the glaucoma change probability
      (GCP). METHODS: A database of stable visual fields, collected within 1 week from
      35 glaucoma patients and within 6 months from 15 normal patients, was used to
      determine confidence intervals for GCP using 4 different methods. The methods
      classified visual field locations on the basis of either defect or mean
      threshold, and used test-retest data or baseline-less-follow-up data to determine
      values for the confidence intervals. The specificity of the 4 methods was
      measured using 3700 locations artificially generated to simulate stable visual
      field data. The sensitivity of the methods was measured using 3330 artificially
      generated locations that decreased in either a linear, curvilinear, or bi-linear
      fashion by 2, 3, or 4 dB per year on average. RESULTS: Using GCP with confidence
      intervals built using the methods described in the literature (on the basis of
      defect and test-retest differences) resulted in a higher specificity than
      techniques based on mean threshold. However, the mean-based methods were more
      sensitive at detecting a decrease in a location. Building confidence intervals
      using the difference between a baseline and the current measurement (baseline
      less-follow-up), rather than test-retest differences, also improved the detection
      of visual field progression. CONCLUSIONS: Stratifying baseline visual field
      measurements based on defect and eccentricity as described in the literature
      results in an unusually high specificity: 98% accuracy in classifying the same
      stable data that generated the 95% confidence intervals, rather than the expected
      95% accuracy. By stratifying measurements based on mean threshold, and using
      baseline-less-follow-up rather than test-retest differences to build 95%
      confidence intervals, sensitivity is increased by 14.1%. This increase in
      sensitivity comes with a corresponding 2.2% decrease in specificity.

PMID- 16988604
TI  - Visual field defects and vision-specific health-related quality of life in
      African Americans and whites with glaucoma.
AB  - PURPOSE: To examine the relationship of visual field impairment to vision
      specific health-related quality of life and symptoms in a large cohort (N=345) of
      African Americans and Whites of non-Hispanic origin diagnosed with glaucoma.
      MATERIALS AND METHODS: Participants consisted of persons > or =55 years of age
      recruited from university-affiliated ophthalmology and optometry practices in
      Birmingham, AL who had been diagnosed with glaucoma. Medical records were
      abstracted to collect information on demographics, visual acuity, and visual
      fields. A telephone survey was conducted to obtain information on vision-specific
      health-related quality of life [National Eye Institute Visual Function
      Questionnaire-25 (NEI VFQ-25)], glaucoma symptoms [Glaucoma Symptom Scale (GSS)],
      and cognitive status (Short Portable Mental Status Questionnaire). Visual fields
      were used to compute a visual field defect score for each eye based on the
      Advanced Glaucoma Intervention Study (AGIS) scoring system. RESULTS: Mean NEI VFQ
      25 subscale scores ranged from the 50s to 80s. Scores for African Americans and
      Whites did not differ except for the general health and ocular pain subscales for
      which African Americans had slightly higher scores. For both African Americans
      and Whites, as the AGIS score became worse in the better and/or worse eye, there
      was a decrease in VFQ subscale score for most VFQ subscales including general
      vision, distance vision, near vision, social functioning, color vision, and
      peripheral vision (P<0.05). AGIS scores were unrelated to the GSS subscales in
      African Americans; for Whites, the visual but not the nonvisual subscale was
      related to AGIS score. CONCLUSIONS: Scores on most subscales of the NEI VFQ-25
      and the 2 subscales of the GSS are highly similar in African Americans and Whites
      of non-Hispanic origin who have been diagnosed with glaucoma. In addition, for
      both African Americans and Whites, the VFQ subscales for the most part
      demonstrated good construct validity with respect to the extent of visual field
      impairment. Results imply that the NEI VFQ-25 and the GSS are appropriate
      instruments for studying the personal burden of glaucoma in studies whose samples
      involve both African American and White adults.

PMID- 16988605
TI  - Costs and utilization of end-stage glaucoma patients receiving visual
      rehabilitation care: a US multisite retrospective study.
AB  - PURPOSE: Glaucoma is a prevalent ophthalmologic disease and leading cause of
      blindness. A retrospective analysis was conducted to evaluate resources and costs
      for end-stage glaucoma patients receiving visual rehabilitation care (VRC).
      MATERIALS AND METHODS: A chart review was conducted in 3 United States VRC
      centers. Charts of patients with primary open-angle glaucoma as the primary cause
      of vision loss (1998 to 2003) were selected, yielding 81 records. Data were
      collected from patient-level billing and reimbursement records
      (ophthalmologist/optometrist visits, glaucoma medications, procedures, and
      specialized low-vision and glaucoma-related services). Visual rehabilitation
      services included utilization of low-vision devices, assessment of daily
      functioning, orientation and mobility training, and patient counseling. RESULTS:
      Mean age at baseline was 72.7 years [standard deviation (SD)=17.2, range: 29 to
      95]. Of those with known sex (n=77), 55.8% were women. Medicare was the payer
      type for most patients (59.3%), whereas 20% had Medicaid. Mean number of visits
      was 7.1 (SD=6.1) in year 1 and 3.7 (SD=4.2) in year 2, for an annual mean of 5.4
      (SD=5.0) visits overall. Total mean cost per patient in year 1 was greater than
      year 2 [$2170 (SD=$2252) vs. $1202 (SD=$1080), respectively]; of the total 2-year
      costs, 15% were VRC, 37% ophthalmology care, and 48% pharmacy. Analysis of
      nonpharmacy costs revealed that VRC accounted for 28% and ophthalmology for 72%.
      CONCLUSIONS: End-stage glaucoma is associated with appreciable resource
      utilization and costs, because of both vision rehabilitation and ophthalmology
      care. Advanced primary open-angle glaucoma has a substantial cost-of-illness,
      warranting improved management in early stages of disease.

PMID- 16988606
TI  - The probability of glaucoma from ocular hypertension determined by
      ophthalmologists in comparison to a risk calculator.
AB  - OBJECTIVE: To investigate the ability of ophthalmologists to estimate an
      individual's risk of converting from ocular hypertension to glaucoma, and to
      compare these estimates to a risk calculator. DESIGN: Cross-Sectional Survey.
      METHODS: Fifty-one ophthalmologists estimated the probability of developing
      glaucoma of 4 factitious patients with ocular hypertension, after a didactic
      review of the Ocular Hypertension Treatment Study (OHTS) results. We compared the
      physician estimates to the probability estimates of a risk calculator on the
      basis of the multivariate Cox proportional hazard model of the OHTS results.
      RESULTS: The average estimates given by the ophthalmologists (mean probability+/
      SD) of developing glaucoma in 5 years for patient no. 1, patient no. 2, patient
      no. 3, and patient no. 4 were 6.5%+/-8.4 (range 1 to 50), 30.6%+/-20.5 (range 1
      to 100), 7.1%+/-5.1 (range 0 to 20), and 21.1%+/-17.3 (range 1 to 80),
      respectively. The risk calculator estimated the probability of glaucoma in these
      same patients to be 13.7%, 53.8%, 5.1%, and 41.9%, respectively. CONCLUSIONS: The
      ophthalmologists showed a high range of estimates for the probability of
      developing glaucoma in the same ocular hypertensive patients. This may lead to
      either under or over treatment of patients. Clinicians need a more exact method
      to determine the probability of glaucoma from ocular hypertension.

PMID- 16988607
TI  - Long-term follow up of surgical repair of late bleb leaks after glaucoma
      filtering surgery.
AB  - PURPOSE: To study the long-term outcomes of surgical revision of leaking blebs
      after trabeculectomy and identify possible risk factors for failure. PATIENT AND
      METHODS: A retrospective, nonrandomized, noncomparative interventional study of
      34 eyes with late bleb leaks after trabeculectomy that underwent bleb excision
      with conjunctival advancement. The primary outcome measure was successful repair
      and control of intraocular pressure (IOP). The other measures evaluated included
      change in visual acuity from baseline and complications such as recurrence of
      bleb leak, endophthalmitis or the need for additional antiglaucoma medication to
      control IOP. RESULTS: After a mean follow up of 36.2+/-23 months, the mean IOP at
      the last visit was 14.5+/-7.6 mm Hg. IOP in 58.8% of eyes was controlled without
      medication. Complications included early leaks (7/34), late recurrent or
      persistent leaks (1/34), and endophthalmitis (1/34). In all, 41.2% patients
      required additional medication at the last visit. Survival analysis at 22 months
      the probability of total and qualified success was 52% and 72%, respectively.
      However, this dropped to 10% and 15%, respectively, at 5 years. The probability
      of total and qualified success further dropped to 2.5% and 5% at 5 years when the
      IOP cut-off was lowered from 21 to 15 mm Hg. Cox regression analysis failed to
      identify risk factors for bleb failure. CONCLUSIONS: Surgical bleb revision seems
      to be effective in treating late bleb leaks with few postoperative complications.
      However, patients should be followed carefully as late failure of bleb function
      beyond 2 years is a significant possibility.

PMID- 16988608
TI  - Intrastromal diathermal keratostomy: a new micropenetrating clear-cornea glaucoma
      procedure.
AB  - PURPOSE: The filtering intrastromal diathermal keratostomy (IDK) was developed to
      comply with the call for a low postoperative intraocular pressure (IOP) and a
      bleb morphology without a thin, cystic appearance. PATIENTS AND METHODS: A
      diathermal microkeratostomy (150 to 200 microm) was created into the anterior
      chamber, anterior to the Schwalbe line through the floor of a surgical
      corneoscleral tunnel incision into the subconjunctival space. A newly developed,
      bipolar diathermal microneedle was used to create the keratostomy, replacing the
      Holmium laser used previously. Subconjunctival injections of 3 microg mitomycin C
      were used in each eye 1 week before the IDK to obtain maximum antiproliferative
      effect at the time of the operation. Nine patients (10 eyes) with complicated,
      refractory primary and secondary open-angle glaucoma are discussed. RESULTS:
      Histologic examination of the IDK and clinical postoperative ultrasound
      biomicroscopy showed an optimal appearance of the diathermal microkeratostomy.
      After 34 months (range 24 to 42 mo) the mean IOP was 11 mm Hg (SD+/-3, range 6 to
      16) without medication in all 10 eyes. IDK revision with internal needling of
      postoperative subconjunctival fibrosis through the tunnel incision was performed
      in 5 eyes after an average of 3 months (range 0.2 to 7 mo). After 33 months
      (range 19 to 38 mo), the postrevision mean IOP was 10 mm Hg (SD+/-2, range 8 to
      14) without medication in all 5 eyes. All 10 eyes showed noncystic diffuse blebs
      with optimal spongy subepithelial morphology: in 2 eyes the blebs were totally
      avascular and in 8 eyes they were relatively avascular. CONCLUSIONS: The
      preliminary results of the new clear-cornea IDK seem promising because of
      postoperative IOP of about 10 mm Hg despite a low dose of mitomycin C and
      noncystic bleb morphology.

PMID- 16988609
TI  - Trabecular bypass: effect of schlemm canal and collector channel dilation.
AB  - PURPOSE: To theorize the effect of Schlemm canal (SC) and/or collector channel
      (CC) dilation combined with a trabecular bypass on intraocular pressure (IOP) in
      eyes with primary open angle glaucoma. METHODS: The elliptic shaped SC is dilated
      in conjunction with a trabecular bypass and its expanded height is largest at the
      bypass and linearly deceases to the nondilated height over the dilated
      circumferential length. The CC dilation is modeled with a reduced outflow
      resistance of second order polynomial over the same dilated length. Equations
      governing the pressure and circumferential flow in SC are solved numerically for
      both the unidirectional and bidirectional bypasses. The reduced IOP is deduced
      from the solution. RESULTS: IOP is reduced substantially with moderate SC
      dilation from the normal height of 20 microm to 40 to 50 microm at the bypass;
      additional IOP reduction diminishes with further dilation. SC dilation is more
      effective for eyes with smaller SC. CC dilation also lower IOP significantly.
      With the trabecular bypass alone, the elevated IOP in primary open angle glaucoma
      is expected to drop to the mid-to-high teens. IOP can be further reduced by
      another 3 to 6 mm Hg with moderate SC and CC dilation. The circumferential length
      of dilated SC affects the efficacy of IOP reduction. In theory, the dilation of
      SC with a trabecular bypass is analogous to a partial trabeculotomy in terms of
      IOP reduction. CONCLUSIONS: In theory, a moderate dilation of SC and CC in
      conjunction with a trabecular bypass reduces the IOP to the low-to-mid teens.

PMID- 16988610
TI  - Phaco-viscocanalostomy versus phaco-trabeculotomy: a middle-term study.
AB  - PURPOSE: To compare the surgical outcomes between phaco-viscocanalostomy and
      phaco-trabeculotomy in open-angle glaucoma. PATIENTS AND METHODS: In a
      nonrandomized, retrospective clinical study, 110 eyes underwent phaco
      viscocanalostomy (VCS group), and 110 eyes underwent phaco-trabeculotomy (LOT
      group). The mean follow-up was 857+/-409 (+/-SD) days (P=0.4777). RESULTS: The
      mean preoperative treated intraocular pressure (IOP) values were 20.2+/-3.5 mm Hg
      in the VCS group and 20.9+/-3.5 mm Hg in the LOT group (P=0.3377). The
      postoperative IOPs in the VCS group were 15.0+/-3.0 and 16.1+/-3.0 mm Hg at 1 and
      3 years, and in the LOT group 16.3+/-2.9 mm Hg (P=0.0088) and 16.5+/-3.3 mm Hg
      (P=0.4993), respectively. The number of medications used in the VCS group was
      significantly lower than in the LOT group during the observation periods (P< or
      =0.0130). The probabilities of achieving IOPs< or =21 mm Hg at 3 years in the VCS
      group were 92.0% with or without mediations and 58.2% without medications, and
      were significantly better than those of the LOT group (84.7% and 36.0%, P=0.0334
      and P<0.0001 by log-rank test, respectively). The probabilities of achieving
      IOPs< or =16 mm Hg at 3 years in the VCS group were 30.5% with or without
      mediations and 30.3% without medications, whereas those in the LOT group were
      27.5% (P=0.1799) and 19.4% (P=0.0010), respectively. The visual outcome was
      similar between the groups. Postoperative hyphema (> or =2 mm) and IOP spikes (>
      or =30 mm Hg) occurred significantly less in the VCS group (2.7 and 3.6%,
      respectively) than in the LOT group (26.4 and 28.2%, respectively; P<0.0001). In
      13 eyes (11.8%) of the LOT group, the highest IOP level was recorded 40 mm Hg or
      higher. Vitreous hemorrhage and central visual loss occurred in 1 case each in
      the LOT group. CONCLUSIONS: After a middle-term observation, phaco
      viscocanalostomy provides better IOP control and a lower incidence of vision
      threatening complications than phaco-trabeculotomy.

PMID- 16988611
TI  - What can patients see during glaucoma filtration surgery under peribulbar
      anesthesia?
AB  - PURPOSE: To describe the visual sensations experienced by patients during
      glaucoma filtration surgery under peribulbar anesthesia and to determine possible
      risk factors that may affect the visual sensations experienced. SETTING: King
      Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. METHODS: In this
      prospective questionnaire study, 75 consecutive adult patients listed for
      glaucoma filtration surgery (trabeculectomy or Ahmed tube implantation) under
      peribulbar anesthesia were interviewed postoperatively about the visual
      sensations experienced in their operated eye during the surgery. RESULTS: The
      mean age of the 75 patients was 59.7 years (range, 27 to 83, SD +/-12.1). Sixty
      five patients (86.7%) perceived light perception during the surgery and the
      overall light intensity fluctuated in 45 patients (60.0%). The mean age of the
      patients who retained light perception intraoperatively was significantly lower
      compared with those who lost light perception (58.3 y vs. 68.8 y; P=0.009). Forty
      six patients (61.3%) were able to perceive colors, 32 patients (42.7%) perceived
      movement, 31 patients (41.3%) saw surgical instruments, and 33 patients (44.0%)
      reported seeing the surgeon's hands or fingers. The severity of glaucoma did not
      affect the proportion of patients who perceived the various visual sensations.
      One patient (1.3%) was frightened by his intraoperative visual experience. Of the
      remaining patients, 53 (70.7%) said the visual sensations did not affect them,
      whereas 21 (28.0%) found them unpleasant. CONCLUSIONS: The majority of patients
      undergoing glaucoma filtration surgery retained light perception intraoperatively
      and many also experienced various visual sensations. Only 1.3% of patients were
      frightened by their visual experience.

PMID- 16988612
TI  - Trabeculectomy with mitomycin C combined with direct cauterization of peripheral
      iris in the management of neovascular glaucoma.
AB  - PURPOSE: To determine the outcomes of trabeculectomy with mitomycin C (MMC)
      combined with direct cauterization of peripheral iris before iridectomy in the
      management of neovascular glaucoma (NVG), and to demonstrate the effect of this
      surgical technique on decreasing the incidence of intraoperative bleeding and
      early postoperative hyphema. METHODS: This prospective study was based on 72 eyes
      of 72 patients with NVG who underwent primary trabeculectomy with MMC combined
      with direct cauterization of peripheral iris before iridectomy. The patients were
      evaluated for intraoperative and early postoperative complications such as
      hyphema, and operative success rates. Operative success was defined as an
      intraocular pressure (IOP) < or =22 mm Hg (+/-medical therapy) in the absence of
      phthisis. The mean IOP and the mean number of antiglaucomatous medications at
      baseline and at the posttrabeculectomy sixth month were compared by paired
      Student t test. RESULTS: The mean preoperative IOP was 39.3+/-5.6 mm Hg (range,
      29 to 60 mm Hg) whereas it was 20.02+/-4.3 mm Hg (range, 14 to 38 mm Hg) at the
      postoperative sixth month. The mean preoperative number of antiglaucoma
      medications was 3.2+/-0.4 (range, 2 to 4) but it reduced to 1.8+/-0.6 (range, 1
      to 4) at the postoperative sixth month. These differences were statistically
      significant (P<0.00001). The IOP was < or =22 mm Hg (+/-medical therapy) in 69
      eyes (95.8%) at the postoperative first week, in 62 eyes (86.1%) at the
      postoperative first month, in 60 eyes (83.3%) at the postoperative third month
      and in 48 eyes (66%) at the postoperative sixth month. Hyphema occurred in 15
      eyes (20.8%) within the first week of the surgery. In 12 eyes it was transient;
      however, in 3 eyes irrigation of anterior chamber was required. CONCLUSIONS:
      Trabeculectomy with MMC combined with direct cauterization of peripheral iris
      decreases the incidence of both intraoperative bleeding, and early postoperative
      hyphema, and provides reduction of IOP and the number of antiglaucomatous
      medications in cases with NVG in a 6-month follow-up period.

PMID- 16988613
TI  - Clinical outcomes of glaucoma treatment over a patient lifetime: a Markov model
      (letter).

PMID- 16988614
TI  - Dynamic contour tonometer versus goldmann applanation tonometer.

PMID- 16988616
TI  - Cholesteatoma, cerebrospinal fluid leakage, and chronic otitis media.

PMID- 16988617
TI  - References in the history of otology: the importance of being earnest.
AB  - BACKGROUND: Historical vignettes are often included in scientific otological
      articles. However, they may contain inaccuracies and errors when authors use
      secondary or compiled texts rather than primary source material. METHODS:
      Examples of errors arising from the use of secondary sources are obtained from
      compiled works in comparison with original publications, with a particular focus
      on Hildanus' speculum. RESULTS: Different types of inaccuracies may be found in
      historical vignettes. In Hildanus' works, two different specula are depicted: one
      was described by himself during his lifetime, and the other after his death,
      probably by his publisher. Only the posthumous description of Hildanus' speculum
      has been retained historically, but it is uncertain that it was really developed
      by Hildanus himself. Other such inaccuracies exist because of confusion with the
      original terminology of referring to an instrument, such as the otoscopes of
      Toynbee and Brunton, inaccuracies in dates, misinterpretation of the original
      text, such as the attribution to Charcot as the first to propose the intracranial
      division of the eighth nerve in Meniere's disease, and problems of translation
      (e.g., the different translations of the book titled Diseases of the Ear by
      Wilhelm Kramer). CONCLUSION: These different examples of inaccuracies show the
      common problems encountered in writing a historical report. Authors must be aware
      of such errors and work almost exclusively with original references. Secondary
      and compiled references should be reserved for a background of discussion and not
      as a source of direct support.

PMID- 16988618
TI  - TH1/TH2 and regulatory cytokines in adults with otitis media with effusion.
AB  - OBJECTIVE: Otitis media with effusion is one of the most common and intractable
      ear diseases. However, the role of Th1, Th2, and immunoregulatory cytokines on
      the pathogenesis of the disease in adult patients remains to be determined. The
      aim of this study is to disclose the cytokine expression in middle ear effusions
      (MEEs) in adults and to compare the profile on the basis of the presence of
      allergic rhinitis and the type of effusions. STUDY DESIGN: A prospective
      controlled clinical study. PATIENTS: MEEs were collected from 80 adult subjects.
      The concentration of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, and interferon
      (IFN)-gamma in MEEs were determined by using enzyme-linked immunosorbent assay.
      RESULTS: IL-2, IL-4, IL-5, IL-10, IL-12, and IFN-gamma in MEEs were detected in
      60 (75.0%), 33 (41.3%), 42 (52.5%), 14 (17.5%), 80 (100%), and 66 (82.5%)
      samples, respectively. Among these cytokines, only the concentration of IL-4 in
      the allergic rhinitis-positive group was significantly higher than that in the
      allergic rhinitis-negative group. On the other hand, IL-2, IL-12, and IFN-gamma
      were detected, regardless of the presence of allergic rhinitis, and the
      concentration of these cytokines correlated with each other. The correlation
      between the concentration of IL-4 and IL-5 was also detected. In addition, both
      the incidence rate and the concentration of IL-10 in MEEs were significantly
      higher in the mucoid type compared with those in the serous type effusions.
      CONCLUSION: Regardless of allergic status, IL-12 may play a critical role in the
      pathogenesis of otitis media with effusion by affecting the production of IL-2
      and IFN-gamma. In addition, IL-4 may have some impact on the immunologic
      condition in adults with allergic rhinitis. IL-10 potentially affects the
      viscosity of MEEs.

PMID- 16988619
TI  - Cross-linked hydrogels for middle ear packing.
AB  - OBJECTIVE: To develop an ideal supportive packing material for ossiculoplasty,
      tympanoplasty, or other otologic procedures. MATERIALS AND METHODS: Several
      materials, namely, Carbylan-SX (P-C; Sentrx Surgical, Inc., Salt Lake City, UT),
      Gelfoam (P-GF; Pharmacia & Upjohn, Kalamazoo, MI), and Merogel (P-MG; Medtronics,
      Inc., Minneapolis, MN), were prepared and then placed into a Hartley guinea pig's
      (Elm Hill, Chelmsford, MA) middle ear cavities through a large myringotomy
      incision. The contralateral ear underwent a large myringotomy without packing
      material being placed. Preoperative and posteroperative auditory brainstem
      response studies were performed using Intelligent Hearing system software. The
      animals were examined weekly. Two weeks after packing placement, the animals were
      killed, and the temporal bones were harvested. Whole temporal bone sectioning was
      performed to analyze the presence of implant, surrounding inflammation, presence
      of osteoneogenesis and fibrosis, or adhesions. RESULTS: All the materials, except
      the P-MG, were easy to place into the middle ear cavity. The P-MG contains woven
      strands that are difficult to trim into the small sizes needed for placement. The
      P-MG group had a smaller average amount of implant present compared with the
      other groups at 2 weeks. The degree of osteoneogenesis was similar among the P
      GF, P-C, and P-MG groups. The P-MG and P-C groups contained the lowest amount of
      fibrosis between the implant and surrounding middle ear structures. CONCLUSION:
      This study demonstrates promising results with P-C as a potential supportive
      packing material for otologic procedures. P-C compares favorably with P-MG and P
      GF in a guinea pig model with respect to ease of placement and amount of
      fibrosis.

PMID- 16988620
TI  - Magnetic properties of middle ear and stapes implants in a 9.4-T magnetic
      resonance field.
AB  - HYPOTHESIS: A 9.4-T magnetic resonance (MR) field may cause motion displacement
      of the middle ear and stapes implants not previously observed with 1.5- and 3.0-T
      magnets. BACKGROUND: Publications have described the safety limitations of some
      otologic implants in 4.7-T field and resulted in several companywide patient
      safety-related recalls. To date, no studies have been reported for otologic
      implants in a 9.4-T MR field nor have comparisons been made with 4.7-T field
      strengths. METHODS: Twenty-three commonly used middle ear and stapes prostheses
      were selected and exposed to 9.4-T MR fields in vitro within petri dishes, and
      eight of the 23 implants were further studied ex corpus in human temporal bones
      (TBs) in a 9.4-T MR field. This study has been approved by the institutional
      review board. RESULTS: Eight prostheses in petri dishes grossly displaced at 9.4
      T, three of which had not previously moved in either the 1.5- or 3.0-T magnets.
      The eight TB preparations showed no avulsions or motion indicators after exposure
      at 9.4 T. CONCLUSION: Middle ear and stapes implants can move dramatically in
      petri dishes at 9.4-T MR field, more so than at 1.5 and 3.0 T. The absence of
      avulsions in the TB group strongly suggests that the surgical means used to
      fixate the middle ear implants to the middle ear structures successfully
      overcomes the magnetic moment produced at MR field strengths up to 9.4 T. The use
      of MR imaging is not contraindicated by this study's findings.

PMID- 16988621
TI  - [Internal carotid artery dissection on arterial fibromuscular dysplasia causing a
      central retinal artery occlusion: a case report].
AB  - INTRODUCTION: We report a case of a 66-year-old woman presenting a central
      retinal artery occlusion with no cardiovascular risk factor, with assessment
      using supra-aortic artery ultrasonography showing total internal carotid artery
      thrombosis. OBSERVATION: When vascular thrombosis risk factors are absent, more
      in-depth assessment such as a supra-aortic artery angioscan can provide the
      diagnosis of arterial dissection on arterial fibromuscular dysplasia. CONCLUSION:
      Central retinal artery occlusion is a rare but severe pathology. Therefore it is
      very important not to neglect the etiological assessment, because it can be the
      revealing element of a severe pathology.

PMID- 16988622
TI  - [Ocular coloboma associated with cervico-oculo-acoustic syndrome].
AB  - INTRODUCTION: Cervico-oculo-acoustic syndrome is an uncommon syndrome consisting
      of Klippel Feil syndrome, deafness, and Duane syndrome. We relate a new case of
      cervico-oculo-acoustic syndrome. CASE REPORT: We report the case of 15-month-old
      girl referred for esotropia of the right eye. Ocular examination revealed type 1
      Stilling Duane syndrome in the right eye, in which we also noted microcornea,
      iris coloboma, and papillary and inferior chorioretinal coloboma sparing the
      macular area. The left eye was normal. The physical examination revealed Klippel
      Feil syndrome characterized by an extremely short neck with limited movement, a
      low posterior head line and fusion of the cervical vertebrae on radiography. The
      association of hearing loss (due to agenesis of the external ear) with Klippel
      Feil syndrome and Stilling Duane syndrome confirmed the diagnosis of cervico
      oculo-acoustic syndrome. CONCLUSION: This case is unique because of the
      association of cervico-oculo-acoustic syndrome with ocular coloboma of the right
      eye. This association has not been reported previously in the literature.

PMID- 16988623
TI  - [Clinical case of management with intravitreal injection of Ranibizumab
      (Lucentis) on AMD predominant occult CNV: 6-month follow-up with FA, ICG-A, and
      OCT].
AB  - INTRODUCTION: Controlled clinical trial results of occult choroidal
      neovascularization (CNV) management in age-related macular degeneration (AMD)
      using intravitreal injections of Ranibizumab have shown significant improvement
      in vision for the treated group. CASE REPORT: The first clinical case of
      minimally classic CNV is reported here with the results at 6 months, not only
      with changes in visual acuity but also with complete imaging at each follow-up
      with fluorescein angiography, infracyanine angiography using the scanning laser
      ophthalmoscope (SLO) and with OCT examination. After the second injection, the
      patient experienced improvement in vision and complete regression of all symptoms
      to date (5 months after the first injection), showing very favorable progression
      during the entire follow-up. CONCLUSION: This clinical case shows extremely
      favorable progression of the minimally classic lesion resulting from the first
      two injections of Lucentis. The situation is now stabilized in terms of function
      and morphology, as shown by the fluorescein and infracyanine SLO angiography and
      OCT examination.

PMID- 16988624
TI  - [Prognostic factors for malignant uveal melanoma. Retrospective study on 2,241
      patients and recent contribution of monosomy-3 research].
AB  - INTRODUCTION: We conducted a retrospective study on the clinical factors
      influencing the local and general prognosis of patients treated for uveal
      melanoma with a preliminary analysis of the prognostic value of monosomy 3.
      PATIENTS: and method: The patients sent to Curie Institute for uveal melanoma
      have a complete initial clinical evaluation, conservative management by
      radiotherapy or enucleation, and local and general long-term follow-up. Over the
      last 5 years, the status of chromosome 3 has been assessed by FISH in the tumors
      of enucleated patients. Findings concerning the initial workup, treatment, and
      follow-up are recorded prospectively. We conducted a retrospective study with
      multivariate analysis of the clinical factors influencing local recurrence,
      ocular conservation metastasis, and survival and studied the effect of monosomy
      3. RESULTS: A total of 2241 patients were registered with a median follow-up of
      72 months. Of these patients, 92.8% had conservative management with iodine 125
      brachytherapy or proton beam therapy and 7.2% of the patients had enucleation
      (n=160). Tumors from 120 patients were studied for the status of chromosome 3 by
      FISH. The overall survival rate was 76.3% and the metastatic rate was 19.5%. The
      clinical factors influencing survival were the size and location of the tumor,
      age of the patient, gender, and initial treatment. The factors influencing the
      metastatic risk were the same plus retinal detachment and local recurrence.
      Monosomy 3 was a significant risk factor for metastatic disease. DISCUSSION: This
      study found the usual risk factors with the difference that location on the
      equator seems to be of worse prognosis than ciliary body involvement for survival
      and metastasis. In addition, the initial retinal detachment appears to be a risk
      factor for local recurrence and metastasis. At present, the evaluation of
      chromosome 3 is available for enucleated tumors but it could probably be done on
      needle biopsy performed during conservative management as well. CONCLUSION: This
      study confirms previous results on the prognostic factors of uveal melanoma and
      on the value of monosomy 3. The increasingly precise identification of a group of
      high-risk patients should allow us to propose adjuvant therapy and to adapt
      follow-up.

PMID- 16988625
TI  - [Surgical management of nontraumatic corneal perforations: an 8-year
      retrospective study].
AB  - PURPOSE: Treatment of nontraumatic corneal perforation is a difficult task. The
      aim of our study was to retrospectively analyze predisposing conditions leading
      to perforation, surgical treatments, and visual outcomes. METHODS: Fifty-six
      patients were admitted in our department for a nontraumatic corneal perforation
      between 1997 and 2004. Mean patient age was 69 years (range, 16-95 years) and the
      mean follow-up was 20.5 months (range, 6-96 months). RESULTS: The diseases
      associated with perforations were neurotrophic ulcer in 24 cases (43%),
      peripheral immunologic ulcer in ten cases (18%), dry eye in six cases (11%), and
      infectious keratitis in seven cases (13%). All patients had specific adapted
      medical treatment before surgery. As a first procedure, we used cyanoacrylate
      glue in 14 cases (50% anatomic success), multilayer amniotic membrane
      transplantation in 23 cases (100% anatomic success), conjunctival flap in six
      cases, peripheral lamellar graft in three cases (33% anatomic success), emergency
      penetrating keratoplasty in 13 cases (31% anatomic success), and one patient's
      eye had to be eviscerated. Several surgical procedures were necessary in 16 cases
      (28%), nine patients needing total conjunctival flap at the end. We were able to
      achieve tectonic stability in 91% of eyes and 32% of patients recovered useful
      visual acuity between 20/400 and 20/50. CONCLUSION: Amniotic membrane
      transplantation is an effective method for managing corneal perforations and
      usually does not need a further reconstructive procedure. Visual outcome is poor
      when peripheral or central keratoplasty are needed. We recommend a conjunctival
      flap when descemetocele or perforation recurs despite previous surgical
      management.

PMID- 16988626
TI  - [Treatment of subfoveal choroidal neovascularization in pathologic myopia with
      photodynamic therapy: outcomes at 1 and 2 years of follow-up].
AB  - PURPOSE: To evaluate the visual outcome of photodynamic therapy with verteporfin
      in patients with subfoveal choroidal neovascularization (CNV) caused by
      pathologic myopia. METHODS: Retrospective and noncomparative analysis of 42
      patients with CNV secondary to pathologic myopia recruited between September 2001
      and 2003, who were treated with a standard regimen of photodynamic therapy with
      verteporfin. RESULTS: Forty-two patients were followed up for 12 months; 15 out
      of 42 completed 24 months of follow-up. Initial visual acuity ranged from 1/10 to
      5/10 with a mean of 1.6/10. Twenty-five (56.7%) eyes had stable or improved
      visual acuity at 12 months with a mean of 2.5/10. In the group of patients who
      completed 24 months of follow-up, six eyes (39.9%) had stable or improved visual
      acuity with a mean of 1.6/10 at 1 year and 1.25/10 at 2 years. The average
      photodynamic therapy treatment required in 1 and 2 years were 1.5 and 2.1,
      respectively, and they are less than those reported by the Verteporfin in
      Photodynamic Therapy (VIP) study. CONCLUSION: Photodynamic therapy with
      verteporfin for subfoveal choroidal neovascularization caused by pathologic
      myopia maintained a visual benefit at 1 and 2 years.

PMID- 16988627
TI  - [Role of conditioning medium cytotoxicity. An example with an intraocular lens
      preloaded in injector].
AB  - INTRODUCTION: Following material vigilance cases encountered with the hydrophilic
      acrylic intraocular lens, ACR6D SE preloaded in the Premier shooter, we studied
      the cytotoxicity of the intraocular lens and its conditioning to identify the
      cytotoxic element. We proposed medical device modification to improve its
      biocompatibility. MATERIALS AND METHODS: Biocompatibility-cytotoxicity assays
      were carried out according to ISO 10993-5 recommendations. Tests were performed
      on the SRA 01/04 human lens epithelial cell line. Neutral red, Hoechst 33342, and
      YO-PRO-1 fluorescent probes were used to assess membrane integrity, total DNA,
      and membrane fluidity, respectively. Materials samples were prepared in culture
      medium according to the ISO 10993-5 elution procedure. Pure saline solutions and
      conditioning liquids were tested directly on cells. RESULTS: The intraocular lens
      and injector were not cytotoxic. Conditioning liquids induced membrane fluidity
      perturbation characteristic of apoptosis. Tests performed on new versions of the
      medical device identified a better adapted conditioning liquid. CONCLUSION: The
      results suggest that the cytotoxicity of the conditioning liquid could explain
      the postoperative complication rate. When we changed the conditioning liquid with
      sterile irrigating solution (i.e., rich divalent cation marine solution), we
      eliminated cellular stress. Fluorescent probes are well adapted to assess medical
      device biocompatibility-cytotoxicity.

PMID- 16988628
TI  - [Expression of intercellular adhesion molecule type 1 in the conjunctiva of
      diabetic patients: a preliminary study].
AB  - PURPOSE: Recent research has incriminated adhesion molecules in the pathogenesis
      of diabetic retinopathy. These molecules have been found to be expressed in many
      cells participating in inflammatory processes and neovascularization. The purpose
      of our investigation was to study the expression of intercellular adhesion
      molecule type 1 (ICAM-1) in the conjunctiva of diabetic patients without
      retinopathy in comparison with normal human conjunctiva. PATIENTS AND METHODS:
      Fifteen conjunctival biopsies were obtained from diabetic patients without
      retinopathy. The ocular fundus examination and retinal fluorescein angiography
      were normal. The normal human conjunctiva were taken from five patients
      undergoing senile cataract surgery. Immunohistochemical analysis consisted of
      indirect immunoperoxidase using the monoclonal antibody ICAM-1. RESULTS: The
      adhesion molecule ICAM-1 was immunolocalized in epithelial, vascular endothelial,
      and inflammatory cells. The expression of this molecule was different in diabetic
      patients for the same duration. In the normal human conjunctiva, the expression
      of ICAM-1 was very low. CONCLUSION: This preliminary study shows that ICAM-1 is
      present in the conjunctiva of diabetic patients without retinopathy and thus may
      add new insights into the pathogenesis of diabetic retinopathy.

PMID- 16988629
TI  - [Efficacy and efficiency of preoperative mydriasis: drops versus ocular insert].
AB  - OBJECTIVE: The primary objective of this study was to compare eye drops and
      inserts in terms of the quality of preoperative mydriasis. The secondary
      objective was to evaluate the safety and ease of use of each modality. PATIENTS
      AND METHODS: Prospective randomized and simple blinded study. Patients were
      randomized into two groups: the insert protocol (atropine 1%, diclofenac 0.1%
      collyrium and Mydriasert) or the eye drop protocol (atropine 1%, diclofenac 0.1%,
      tropicamide 0.5%, and phenylephrine 10% collyrium). Fifty-one patients were
      included: 25 in the insert protocol and 26 in the drop protocol. Mydriasis
      quality was evaluated by nurses and surgeons. The ease of use was estimated by
      the number of gestures required to obtain mydriasis and the difficulties
      encountered. Safety was evaluated at the patient's bedside. RESULTS: Mydriasis of
      at least 6 mm was obtained in 92% of the patients in the insert protocol (23/25)
      and 85% of the patients in the drop protocol (22/26) (NS). Four patients lost
      their insert during the study. Of the patients in the insert group, 16% (4/25)
      experienced stinging in their eyes, as did 23% (6/26) of patients in the group
      using drops (NS). To reach effective mydriasis, the insert protocol required
      fewer nurse gestures per patient than the drop protocol (3.0 versus 8.3;
      p<0.001). CONCLUSION: With the protocol using an insert, preoperative mydriasis
      is not inferior to that obtained with drops only and is more efficient in terms
      of nurse time and number of gestures. Nurses should be trained in appropriate
      handling of the insert and avoiding the loss of the device.

PMID- 16988630
TI  - [SPA-1: semiology for phenotyping AMD: precursors].
AB  - PURPOSE: A reliable classification of AMD subgroups is necessary prior to any
      genetic or clinical investigation. For this purpose, we evaluated a selected list
      of items for AMD based on color photographs of the fundus but also on fluorescein
      and ICG angiographies and OCT. The first step (SPA-1) is to evaluate the
      interobserver agreement for AMD precursors. METHODS: The 30 items for AMD
      precursors, choroidal neovascularization and atrophy, were chosen from the
      literature. We selected 20 eyes from 20 consecutive patients affected by various
      forms of these precursors from the prospective NAT-2 study. Grading was based on
      color photographs of fundus, red-free frames, and fluorescein angiography. For
      each eye, five grids were filled in by four independent, experienced readers from
      our reading center and one expert. Within-subject variance was studied. RESULTS:
      Within subject variance showed the greatest agreement between graders for
      drusenoid pigment epithelial detachment (variance=0.000). The worst value for
      within subject variance (0.255) was recorded for the item "intermediate drusen
      between 5 and 20." CONCLUSION: This evaluation of our first grid for AMD
      precursors shows high agreement between graders for most of the items. The item
      with the lowest agreement should be modified according to the comments of the
      physicians. This grid could be implemented for phenotypic classification of ARM
      and AMD in future clinical or genetic studies.

PMID- 16988631
TI  - [Frequency of recurrence after Verteporfin photodynamic therapy in AMD].
AB  - INTRODUCTION: Photodynamic treatment (PDT) with verteporfin is used to treat
      choroidal subfoveal neovascularization in age-related macular degeneration (AMD).
      However, the impact of recurrence after PDT on functional results has not been
      assessed, although it was previously shown to be higher than 50% after thermal
      laser treatment for juxtafoveal lesions, and visual prognosis was dramatically
      worsened by recurrence of choroidal neovascularization. METHOD: Sixty-nine
      consecutive patients treated with PDT for CNV in AMD were followed every 3 months
      for up to 3 years. RESULTS: The observed recurrence rate was 17.4%. Recurrence
      was not associated with a decrease in visual acuity The average number of
      treatments was 3.0, increasing to 4.9 in case of recurrence. CONCLUSION: The
      recurrence rate is significantly lower after PDT than after thermal laser. It
      does not have a negative impact on functional outcome.

PMID- 16988632
TI  - [Surgical treatment of persistent macular edema in retinal vein occlusion].
AB  - INTRODUCTION: Persistent macular edema (ME) is the main cause of poor visual
      outcome in nonischemic retinal vein occlusion (RVO). The aim of this study was to
      evaluate the results of surgery in this disorder. PATIENTS AND METHODS:
      Retrospective nonrandomized comparative pilot study. Visual acuity measurement,
      fluorescein angiography, and optical coherence tomography were performed before
      and after treatment, at 3 months, 6 months, and 1 year. RESULTS: The study
      included 42 eyes: 15 eyes underwent vitrectomy with peeling of the posterior
      hyaloid and/or the internal limiting membrane, 19 received intravitreous
      injection of triamcinolone (IVT), and four had a combination of both treatments.
      In the vitrectomy group, 63% of the eyes showed a progressive decrease of ME
      throughout the year of follow-up (p<0.05 at 1 month and 1 year) and an increase
      in visual acuity (p<0.05 at 3 and 6 months); no complication occurred. In the IVT
      group, the eyes showed a rapid improvement in vision and in ME at 1 month
      (p=0.007 and p=0.001, respectively) but with a frequent ME recurrence at 4
      months; however, 31% of eyes showed durable improvement. Complications after IVT
      were pseudo-endophthalmitis (one eye), transient hypertony (53%), and a full
      thickness macular hole (one eye). In the group treated with vitrectomy combined
      with IVT, ME decreased rapidly and durably, but vision did not improve in this
      small subgroup of long-lasting RVO with prior pigment epithelial changes.
      CONCLUSION: In some eyes, vitrectomy seems to have a more durable effect than IVT
      alone. Further randomized and controlled studies are needed to confirm these
      results and to compare them to the natural course of the disease.

PMID- 16988633
TI  - [Treatment of retinal detachments with giant retinal tear. Retrospective study of
      23 cases].
AB  - PURPOSE: Report of anatomic and functional results of retinal detachment with
      giant retinal tear. PATIENTS AND METHODS: Retrospective study of 23 cases of
      retinal detachment resulting from retinal tear of 90 degrees or more: five had a
      history of ocular trauma, 14 had myopia, and six had no risk for giant retinal
      tear. Episcleral surgery was performed on cases of giant retinal tear less than
      180 degrees , with no advanced proliferative vitreoretinopathy and no inversion
      of the retinal flap. A vitrectomy was performed on other cases. Scleral buckle
      was associated with vitrectomy in cases of advanced vitreoretinopathy. RESULTS:
      The degree of success in the primary surgery was 50% in vitreoretinal surgery,
      75% in vitreoretinal surgery with an encircling scleral buckle, and 86.4% in
      episcleral surgery. Of the seven failed cases, six patients underwent second
      intention surgery: vitrectomy in four cases (primary surgery: the first case,
      episcleral surgery; the next two cases, vitrectomy; and in the fourth, vitrectomy
      with an encircling scleral buckle). In the last two cases, vitrectomy with
      scleral buckle was used (the primary surgery in both cases was vitreoretinal
      surgery). The final success rate was 78.2%, and the average follow-up was 32
      months. Through the last test, postsurgery acute vision improved in 16 cases.
      CONCLUSION: Vitrectomy is often recommended to repair retinal detachment with
      giant retinal tear. However, episcleral surgery can be used if the giant tear is
      less than 180 degrees , the proliferative vitreoretinopathy is not advanced, and
      the retina flap is not inverted. The scleral buckle must be associated with the
      vitrectomy in cases of inferior giant retinal tear even if the proliferative
      vitreoretinopathy is not advanced.

PMID- 16988634
TI  - [Assessment of the Quantel Medical 20-Mhz Ultrasound Cinescan in intraocular
      measurements].
AB  - BACKGROUND AND OBJECTIVE: Evaluation of the Quantel Medical 20-MHz Ultrasound
      Cinescan using a closed transducer in intraocular measurements and its
      reproducibility. PATIENTS AND METHODS: We measured sulcus-to-sulcus distance of
      40 control eyes using the20-MHz Cinescan. Then we compared the sonography to the
      Oculus Pentacam based on the Scheimpflug principle in the measurements of
      anterior chamber depth, cornea-to-implant distance, and implant-to-crystallin
      lens distance in patients who underwent phakic implantation (56 eyes). RESULTS:
      With this technique, the sulcus-to-sulcus distance can be measured with a
      reproducibility of 86%-88% (p<0.05). The authors show that the corneal diameter
      is not correlated with the sulcus measurement (R=24%, p<0.05). DISCUSSION:
      Several techniques are used to quantify anterior segment biometry. Some of these
      methods, such as White-to-White, are too empirical and others, such as the
      Scheimpflug camera - for example the EAS-1000 (Nidek) - or high-frequency
      ultrasound - Ultrasound BioMicroscopy UBM P45 (Paradigm) - are too expensive. The
      20-MHz Cinescan has good reproducibility and provides easier access to anterior
      segment biometry. CONCLUSION: The 20-MHz Cinescan appears to be an accessible
      technique that may become a useful tool in the refractive surgery of the phakic
      intraocular lens.

PMID- 16988635
TI  - [Triamcinolone-assisted vitrectomy in the treatment of recurrent retinal
      detachment due to myopic macular hole].
AB  - PURPOSE: To report the use of triamcinolone-assisted vitrectomy to assess the
      cause of vitrectomy failure in the treatment of retinal detachment due to myopic
      macular hole. OBSERVATIONS: We report the cases of three myopic patients
      presenting with recurrent retinal detachment due to macular hole after initial
      vitrectomy treatment with posterior vitreous detachment, a systematic attempt at
      membrane peeling, and gas injection (SF6). No retinal traction or tear other than
      the macular hole was observed. The recurrence of retinal detachment was treated
      with vitrectomy and intraoperative use of triamcinolone, which demonstrated
      persistent posterior hyaloid and thin and strongly adherent membrane remnants in
      each case. Anatomic success was obtained after peeling these structures.
      CONCLUSION: Intraoperative use of triamcinolone reduces the risk of overlooking
      hyaloid or membrane remnants during vitrectomy for the treatment of myopic
      retinal detachment. Transparent remnants of posterior hyaloid and membranes were
      visualized by triamcinolone-assisted vitrectomy. They could lead to traction on
      the retina and explain the failure of the initial vitrectomy. Anatomic success
      was obtained after peeling these structures.

PMID- 16988636
TI  - [Conjunctival provocation test: recommendations].
AB  - The diagnosis of ocular allergy, which has become a real public health problem
      occurring in 25% of the general population and continues to rise, requires
      allergic testing. Skin and blood tests combined with interviewing the patient
      demonstrate sensitivity to one or more antigens. However, while allergic testing
      and interviews generally reveal the cause of the symptoms, only the conjunctival
      provocation test (CPT) provides clear evidence of a functional relation between
      the conjunctival pathology and exposure to the antigen. Since there is still no
      validated consensus regarding the criteria for positivity of the CPT in routine
      practice, the working group attempted to establish the major guidelines for
      conducting the test, to standardize approaches and pinpoint areas of uncertainty.
      The group established a consensus regarding the conditions for using the test
      (patient selection, allergens to be tested, usable concentrations, the test
      protocol, the signs and symptoms to be assessed, interpretation of results,
      follow-up) and identified two distinct patient groups (outpatients and
      hospitalized patients) in whom test-taking conditions are different. The
      outpatient group includes patients suffering from benign forms of conjunctivitis
      (acute, seasonal, or chronic) and those sensitive to the usual allergens (mainly
      domestic and airborne). In these cases, the test is given in a medical setting
      with an allergologist or an ophthalmologist who instills the drops relatively
      rapidly. The criterion for positivity is the extent of the pruritus. On the other
      hand, in the hospital population, which is composed of patients suffering from
      vernal conjunctivitis, the attempt to establish the triggering factor requires a
      more elaborate protocol carried out in an ophthalmologic setting and based on the
      association of a range of clinical and biological factors. The deliberations of
      the working group should lead to the standardization of the CPT procedure for
      diagnostic purposes.

PMID- 16988637
TI  - [Consequences of glaucoma on circadian and central visual systems].
AB  - Glaucoma is a chronic optic neuropathy leading to a degeneration of retinal
      ganglion cells. There is accumulating evidence that glaucomatous damage extends
      from retinal ganglion cells to vision centers in the brain. Degenerative changes
      are observed in magnocellular, parvocellular, and koniocellular pathways in the
      lateral geniculate nucleus, and these changes are related to intraocular pressure
      and the severity of optic nerve damage. In addition, recent studies show that
      there are also changes in the visual cortex in relation to varying degrees of
      retinal ganglion cell loss. In a rat model of glaucoma, we have recently
      demonstrated a reduction of retinal projections of retinal ganglion cells, not
      only on the visual system but also on the suprachiasmatic nucleus. Human studies
      suggest that the ganglion cell degeneration caused by glaucoma could lead to a
      lesion of the retinohypothalamic tract, which permits the synchronization of
      circadian rhythms.

PMID- 16988638
TI  - [Axenfeld syndrome].

PMID- 16988639
TI  - Malaria--Great Exuma, Bahamas, May-June 2006.
AB  - Malaria in humans is caused by four distinct protozoan species of the genus
      Plasmodium (P. falciparum, P. vivax, P. ovale, and P. malariae). These parasites
      are transmitted by the bite of an infective female Anopheles mosquito. In the
      Caribbean region, malaria has been eliminated from all islands except Hispaniola,
      the island consisting of Haiti and the Dominican Republic. Elimination of malaria
      elsewhere resulted from a combination of integrated control measures,
      socioeconomic development, and close public health surveillance. However, even
      Caribbean islands where malaria is no longer endemic remain at constant risk for
      reintroduction of the disease because of their tropical climate, presence of
      competent malaria vectors, and proximity to other countries where malaria is
      endemic. This susceptibility was underscored by the recent outbreak of malaria on
      the island of Great Exuma in the Bahamas; during May-June 2006, a total of 19
      malaria cases were identified. Four of the cases, in travelers from North America
      and Europe, are described in this report; such cases of imported malaria can
      signal the presence of a malaria problem in the country visited and thus assist
      local health authorities in their investigations. On September 19, after 3 months
      with no report of new cases, CDC rescinded its previous recommendation that U.S.
      based travelers take preventive doses of the antimalarial drug chloroquine
      before, during, and after travel to Great Exuma.

PMID- 16988640
TI  - Inadvertent misadministration of meningococcal conjugate vaccine--United States,
      June-August 2005.
AB  - During June-August 2005, CDC and the Food and Drug Administration (FDA) were
      notified of seven clusters of inadvertent subcutaneous (SC) misadministration of
      the new meningococcal conjugate vaccine (MCV4, Menactra) (Sanofi Pasteur, Inc.,
      Swiftwater, Pennsylvania), which is licensed for intramuscular (IM)
      administration only. A total of 101 persons in seven states were reported to have
      received MCV4 by the SC route. Of these, 100 were contacted by their health-care
      providers and advised of the administration error. CDC conducted an investigation
      to determine whether SC administration of MCV4 resulted in a protective
      immunologic response. This report describes the results of that investigation,
      which indicated that, despite the misadministration, persons vaccinated by the SC
      route were sufficiently protected and that revaccination was not necessary.

PMID- 16988641
TI  - Effects of measles-control activities--African region, 1999-2005.
AB  - In 1999, of approximately 871,000 deaths from measles worldwide, 61% occurred in
      sub-Saharan Africa. In 2001, countries in the World Health Organization (WHO)
      African Region began an accelerated measles-control program to reduce by half by
      2005 the number of deaths that were caused by measles in 1999. The African Region
      accelerated measles-control program was based on four strategies: improving
      routine vaccinations; providing a second opportunity for measles vaccination
      through a routine, 2-dose vaccination schedule or through supplementary
      immunization activities (SIAs); improving measles case management; and
      establishing case-based surveillance with laboratory confirmation for all
      suspected measles cases. Seven countries in the region had already completed
      catch-up SIAs by 2000, before the regional program began; in 2001, additional
      countries in the region began implementing catch-up, and later, follow-up SIAs,
      and steps were taken to improve routine vaccination coverage with measles vaccine
      and other vaccines in the Expanded Programme on Immunization schedule. This
      report summarizes the nationwide SIAs and other measles-control activities
      conducted in the WHO African Region during 1999-2004, analyzes the trends in
      reported measles cases since 1990, and compares the annual number of measles
      cases reported in 2005 with those reported in 1999.

PMID- 16988642
TI  - Update: influenza activity--United States and worldwide, May 21-September 9,
      2006.
AB  - In the United States, CDC uses seven systems for national influenza surveillance,
      four of which operate year-round: 1) the World Health Organization (WHO) and the
      National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating
      laboratory systems; 2) the U.S. Influenza Sentinel Provider Surveillance System;
      3) the 122 Cities Mortality Reporting System; and 4) a national surveillance
      system that records pediatric deaths associated with laboratory-confirmed
      influenza. Data from these four systems are included in this report.

PMID- 16988643
TI  - Revised recommendations for HIV testing of adults, adolescents, and pregnant
      women in health-care settings.
AB  - These recommendations for human immunodeficiency virus (HIV) testing are intended
      for all health-care providers in the public and private sectors, including those
      working in hospital emergency departments, urgent care clinics, inpatient
      services, substance abuse treatment clinics, public health clinics, community
      clinics, correctional health-care facilities, and primary care settings. The
      recommendations address HIV testing in health-care settings only. They do not
      modify existing guidelines concerning HIV counseling, testing, and referral for
      persons at high risk for HIV who seek or receive HIV testing in nonclinical
      settings (e.g., community-based organizations, outreach settings, or mobile
      vans). The objectives of these recommendations are to increase HIV screening of
      patients, including pregnant women, in health-care settings; foster earlier
      detection of HIV infection; identify and counsel persons with unrecognized HIV
      infection and link them to clinical and prevention services; and further reduce
      perinatal transmission of HIV in the United States. These revised recommendations
      update previous recommendations for HIV testing in health-care settings and for
      screening of pregnant women (CDC. Recommendations for HIV testing services for
      inpatients and outpatients in acute-care hospital settings. MMWR 1993;42[No. RR
      2]:1-10; CDC. Revised guidelines for HIV counseling, testing, and referral. MMWR
      2001;50[No. RR-19]:1-62; and CDC. Revised recommendations for HIV screening of
      pregnant women. MMWR 2001;50[No. RR-19]:63-85). Major revisions from previously
      published guidelines are as follows: For patients in all health-care settings HIV
      screening is recommended for patients in all health-care settings after the
      patient is notified that testing will be performed unless the patient declines
      (opt-out screening). Persons at high risk for HIV infection should be screened
      for HIV at least annually. Separate written consent for HIV testing should not be
      required; general consent for medical care should be considered sufficient to
      encompass consent for HIV testing. Prevention counseling should not be required
      with HIV diagnostic testing or as part of HIV screening programs in health-care
      settings. For pregnant women HIV screening should be included in the routine
      panel of prenatal screening tests for all pregnant women. HIV screening is
      recommended after the patient is notified that testing will be performed unless
      the patient declines (opt-out screening). Separate written consent for HIV
      testing should not be required; general consent for medical care should be
      considered sufficient to encompass consent for HIV testing. Repeat screening in
      the third trimester is recommended in certain jurisdictions with elevated rates
      of HIV infection among pregnant women.

PMID- 16988644
TI  - Child overweight in France and its relationship with physical activity, sedentary
      behaviour and socioeconomic status.
AB  - OBJECTIVE: (1) To assess the prevalence of childhood overweight (OW) and obesity
      in France; (2) to examine how physical activity and sedentary behaviour are
      involved in the association between socioeconomic status (SES) and OW, while
      taking into account total energy intake. DESIGN AND SUBJECTS: Representative
      sample of French children aged 3-14 years (n=1016) taken from the 1998-1999 cross
      sectional French INCA (Enquete Individuelle et Nationale sur les Consommations
      Alimentaires) food consumption survey. MEASUREMENTS: Weight and height, leisure
      time physical activity (LTPA), sedentary behaviour (TV viewing and video-game
      use), and SES were reported by parents or children by answering questionnaires;
      total energy intake was assessed using a 7-day food record. RESULTS: In total,
      15.2% (95% CI: 13.0-17.6) of the children are OW (including obese), according to
      the IOTF (International Obesity Task Force) definition. OW is inversely
      associated with SES in children over 6 years of age. LTPA is negatively
      correlated to OW among the 3 to 5-year-old children only, whereas sedentary
      behaviour is positively related to OW in childhood and adolescence. From 6 years
      old on, SES is inversely associated with sedentary behaviour, which consequently
      may partly mediate the relationship between SES and OW. CONCLUSION: This study
      confirms the association between SES, sedentary behaviour and childhood OW in
      France. It was performed before the launching of the French Program of Nutrition
      and Health (PNNS) in 2001 and will be repeated in 2006. This will contribute to
      monitoring both childhood OW and its main determinants at the population scale.

PMID- 16988645
TI  - Overweight men's motivations and perceived barriers towards weight loss.
AB  - OBJECTIVE: To explore motivation and perceived barriers towards weight loss among
      Danish men. DESIGN: The study was of an explorative nature, using qualitative
      focus group interviews as a method. SETTING: Copenhagen, Denmark. SUBJECTS:
      Twenty-two overweight men, at the age of 25-44 years and motivated for weight
      loss, were recruited and distributed into four focus groups. The men were
      primarily unskilled workers. Overall 13 men participated and each group contained
      three or four participants. INTERVENTION: The interview guide was partly
      structured, partly unstructured and the themes of the interviews were motives and
      perceived barriers towards weight loss. RESULTS: Main barriers for losing weight
      appeared to be lack of motivation and the perception of the slimming diet. The
      men had a desire to have a lean appearance and avoid illness, but in all the
      interviews it appeared that the strongest motive for losing weight was a strong
      desire to become more effective and a greater asset for one's workplace.
      Overweight subjects were considered less effective and attractive for the labour
      market. CONCLUSION: This study indicates that if men from lower socioeconomic
      backgrounds are to be motivated to weight loss the focus should not be on
      leanness and good health but rather on increased effectiveness and performance,
      and the arena should include the working place. SPONSORSHIP: The Royal Veterinary
      and Agricultural University supplied the necessary equipment and conference
      rooms.

PMID- 16988646
TI  - Trends in overweight and obesity and changes in the distribution of body mass
      index in schoolchildren of Jena, East Germany.
AB  - OBJECTIVE: Data of Jena children (Germany) show increases in the prevalence
      estimates of overweight and obesity between 1975 and 2001. Our objective was to
      determine if these increases contribute to changes in the distribution of body
      mass index (BMI) in the entire population of children. The decade 1985-1995,
      which includes the time of German reunification, is of particular interest
      because of the significant socio-economic changes in East Germany, in which Jena
      is located. DESIGN AND SUBJECTS: The analyses were based on data from four cross
      sectional growth studies in 7- to 14-year-old children performed in Jena,
      Germany, in 1975 (n=2013), 1985 (n=1534), 1995 (n=1906) and 2001 (n=1918).
      Overweight and obesity were estimated by German reference data and the reference
      of Cole et al. Mean difference plots were used to investigate the changes in the
      BMI distributions within sexes between the studies. RESULTS: Between 1985 and
      1995, the prevalence of overweight and obesity increased significantly in both
      sexes, whereas nonsignificant changes were found between 1975 and 1985. Although
      there is a tendency towards increased overweight between 1995 and 2001, the
      differences were nonsignificant. Comparing data from 1975 and 1985, the mean
      difference plots showed virtually no changes in the BMI distribution. In the
      plots comparing the BMI distribution for 1985 data and 1995 data, the whole
      distribution tended to shift upwards with a greater shift in the upper BMI range.
      The entire population of children in Jena gained weight during this period of
      time. This increase may be linked to a transition towards a more Western
      lifestyle, that is, usually by lower energy expenditure and nutritional
      transitions, caused by the process of reunification of Germany in 1989.
      CONCLUSIONS: Weight gain appears to be a characteristic feature of the entire
      population studied and does not seem to be a separate problem of the obese
      children. This suggests that reported changes in the prevalence may be
      underestimating the looming public health crisis.

PMID- 16988647
TI  - Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid.
AB  - OBJECTIVES: To determine and compare the gastrointestinal (GI) responses of young
      adults following consumption of 45 g sucrose, 20, 35 and 50 g xylitol or
      erythritol given as a single oral, bolus dose in a liquid. DESIGN: The study was
      a randomized, double-blind, placebo-controlled study. SUBJECTS: Seventy healthy
      adult volunteers aged 18-24 years were recruited from the student population of
      the University of Salford. Sixty-four subjects completed the study.
      INTERVENTIONS: Subjects consumed at home without supervision and in random order,
      either 45 g sucrose or 20, 35 and 50 g erythritol or xylitol in water on
      individual test days, while maintaining their normal diet. Test days were
      separated by 7-day washout periods. Subjects reported the prevalence and
      magnitude of flatulence, borborygmi, bloating, colic, bowel movements and the
      passage of faeces of an abnormally watery consistency. RESULTS: Compared with 45
      g sucrose, consumption of a single oral, bolus dose of 50 g xylitol in water
      significantly increased the number of subjects reporting nausea (P<0.01),
      bloating (P<0.05), borborygmi (P<0.005), colic (P<0.05), watery faeces (P<0.05)
      and total bowel movement frequency (P<0.01). Also 35 g of xylitol increased
      significantly bowel movement frequency to pass watery faeces (P<0.05). In
      contrast, 50 g erythritol only significantly increased the number of subjects
      reporting nausea (P<0.01) and borborygmi (P<0.05). Lower doses of 20 and 35 g
      erythritol did not provoke a significant increase in GI symptoms. At all levels
      of intake, xylitol produced significantly more watery faeces than erythritol:
      resp. 50 g xylitol vs 35 g erythritol (P<0.001), 50 g xylitol vs 20 g erythritol
      (P<0.001) and 35 g xylitol vs 20 g erythritol (P<0.05). CONCLUSIONS: When
      consumed in water, 35 and 50 g xylitol was associated with significant intestinal
      symptom scores and watery faeces, compared to the sucrose control, whereas at all
      levels studied erythritol scored significantly less symptoms. Consumption of 20
      and 35 g erythritol by healthy volunteers, in a liquid, is tolerated well,
      without any symptoms. At the highest level of erythritol intake (50 g), only a
      significant increase in borborygmi and nausea was observed, whereas xylitol
      intake at this level induced a significant increase in watery faeces.

PMID- 16988648
TI  - Validation of a self-completion measure of breakfast foods, snacks and fruits and
      vegetables consumed by 9- to 11-year-old schoolchildren.
AB  - OBJECTIVE: To evaluate the validity and reliability of a dietary recall
      questionnaire, designed for group-level comparisons of foods eaten at breakfast
      and intake of fruits, vegetables, sweet items and crisps. DESIGN: Validity was
      assessed relative to 24-h dietary recall interviews, and reliability by comparing
      the baseline data with 4-month follow-up data. SUBJECTS AND SETTING: Fifty-eight
      schools took part in the validity assessments, with 374 children completing both
      measures. Reliability was assessed using 29 schools, with 1233 children at
      baseline and 1033 at follow-up. Children were aged 9-11 years and schools were
      located in socio-economically deprived areas of Wales. RESULTS: Results indicated
      moderate to substantial agreements for most foods eaten at breakfast on the day
      of reporting and fair to moderate agreements for breakfast foods the previous
      day. For items throughout the rest of the previous day, agreement was fair to
      substantial during school hours, but slight after school. Correlations were
      moderate in terms of 'healthy' items and 'unhealthy' items consumed at breakfast
      on the day of reporting, but weaker for the previous breakfast. Correlations
      between measures in terms of fruits, vegetables, sweet items and crisps
      throughout the rest of the previous day were fair to moderate. The measure
      demonstrated fair to substantial group-level reliability. CONCLUSIONS: The
      questionnaire, while subject to a number of limitations, gives an adequately
      valid and reliable overview of selected aspects of children's diet. It is likely
      to be of value at group-level in randomized controlled trials of school-based
      interventions.

PMID- 16988649
TI  - Associations of iron status with dietary and other factors in 6-year-old
      children.
AB  - OBJECTIVE: To investigate the associations of iron status at 6 years of age with
      dietary and other factors. DESIGN: In a cross-sectional study, children's dietary
      intakes (3-day weighed food record) were recorded, body size was measured and
      blood samples were taken near their sixth birthday. SUBJECTS: A sample of 188
      children, from two previous studies (cohorts 1 and 2), was contacted, and 139
      (74%) agreed to participate. RESULTS: Multiple regression analyses with dietary
      and other factors showed that meat and fish consumption, multivitamin/mineral
      supplement intake (both positively) and cow's milk product consumption
      (negatively) were associated with log serum ferritin (SF) (adjusted R (2)=0.125;
      P=0.028; n=129), and juices and residence (rural>urban) with haemoglobin (Hb)
      (adjusted R (2)=0.085; P=0.034; n=127). Of 21 multivitamin/mineral consumers,
      none had depleted iron stores compared to 21 iron-depleted of 108 non-consumers
      (P=0.024). Children living in rural areas (<10,000 inhabitants) (n=33) had higher
      mean corpuscular volume (MCV) (83.3+/-2.3 fl) than those living in urban areas
      (>10,000 inhabitants) (82.1+/-3.2 fl; n=103) (P=0.048). Multiple regression
      analyses with dietary and other factors and growth showed in cohort 1 that
      residence (rural>urban), weight gain 0-1years (negatively), and meat and fish
      intake (positively) were associated with Hb (adjusted R (2)=0.323; P=0.030;
      n=51), meat and fish (positively) with both log SF (adjusted R (2)=0.069;
      P=0.035; n=52) and MCV (adjusted R (2)=0.064; P=0.035; n=52), and in cohort 2
      cow's milk product consumption (negatively) was associated with log SF (adjusted
      R (2)=0.119; P=0.017; n=41) and residence (rural>urban) with MCV (adjusted R
      (2)=0.102; P=0.025; n=41). CONCLUSIONS: Consumption of meat and fish and possibly
      also juices, as well as multivitamin/mineral intake might affect iron status in 6
      year-old children positively, whereas cow's milk product consumption might affect
      iron status negatively. Slower growth in the first year of life and rural
      residence are positively related to iron status of 6-year-olds.

PMID- 16988650
TI  - Folate, vitamin B12 and total homocysteine levels in neonates from Brazil.
AB  - OBJECTIVE: To determine folates, vitamin B12 and total homocysteine levels among
      neonates from mothers of low or high socioeconomic status. DESIGN: We carried out
      a cross-sectional transversal study comprising 143 neonates from two maternity
      hospitals in the city of Salvador, Northeast of Brazil. Cord blood samples were
      obtained at the time of delivery from newborns from low (group 1, n=77) or high
      (group 2, n=66) socioeconomic status. The vitamin B12 and folates were analyzed
      by electrochemiluminescence immunoassay and by a competitive test using a natural
      folate-binding protein (FBP), respectively. Total homocyteine levels were
      measured by fluorescence polarization immunoassay. Maternal environmental risk
      factors for pregnancy complications were obtained from all mothers. RESULTS: Only
      2% of women from group 1 received prenatal care/vitamin supplementation, whereas
      almost all mothers from group 2 (96%) were properly followed. Anemia and/or
      infections pre- or during pregnancy was more prevalent among mothers of babies
      from group 1. Folate levels among newborns from group 1 and 2 were 7.38+/-2.71
      and 8.83+/-4.06 ng/ml, respectively. No difference in the vitamin B12 levels was
      determined between groups. In addition, tHcy serum levels were higher among
      newborns from group 1 compared to those from group 2 (8.54+/-4.06 vs 6.35+/-1.33
      micromol/l, respectively; P=0.005). CONCLUSION: These results demonstrate that
      unprivileged young woman has limited accesses to prenatal care, present high-risk
      factors that hamper both maternal and newborn health. Maternal and newborn health
      status could be improved by simply reinforcing the use of folate-enriched diet.
      The work presented illustrates the challenges that developing countries have to
      face in order to provide preventive adequate health care to the population at
      large.

PMID- 16988651
TI  - Arabinoxylan consumption decreases postprandial serum glucose, serum insulin and
      plasma total ghrelin response in subjects with impaired glucose tolerance.
AB  - OBJECTIVE: Arabinoxylan (AX) consumption is associated with metabolic improvement
      during diabetes and with modulation of ghrelin, an orexigenic gut hormone. The
      effect of AX consumption on ghrelin secretion in disturbed metabolic states is
      unknown. Therefore, we investigated the postprandial responses to AX consumption
      of serum glucose, insulin and triglycerides and plasma total and acylated ghrelin
      in subjects with impaired glucose tolerance (IGT). DESIGN: Randomized, single
      blind, controlled, crossover intervention trial. SUBJECTS: Seven female and four
      male adults with IGT, aged 55.5 years, and body mass index (BMI) 30.1 kg/m(2).
      INTERVENTION: Subjects received either placebo or 15 g AX supplement for 6 weeks
      with a 6-week washout period in-between. MAIN OUTCOME MEASUREMENTS: Postprandial
      responses of serum glucose, insulin and triglycerides, and plasma total and
      acylated ghrelin after a liquid meal challenge test (LMCT) measured at the
      beginning and at the end of the dietary intervention at -20, -5, 0, 15, 30, 45,
      60, 90, 120, 150, 180, 210 and 240 min. RESULTS: After LMCT, AX consumption
      resulted in lower postprandial responses in serum glucose, insulin and
      triglycerides (P<0.05). Compared to placebo, total plasma ghrelin was also
      reduced by 42+/-8 pg/ml (P<0.001) after AX consumption with no difference in
      plasma acylated ghrelin. CONCLUSION: AX consumption improved postprandial
      metabolic responses after an LMCT in subjects with IGT and reduced total ghrelin
      response. However, acylated ghrelin responses were unchanged, suggesting that the
      acylated ghrelin-mediated orexigenic regulation is not improved as only total
      plasma ghrelin decreased.

PMID- 16988652
TI  - Non-conducting functions of voltage-gated ion channels.
AB  - Various studies, mostly in the past 5 years, have demonstrated that, in addition
      to their well-described function in regulating electrical excitability, voltage
      dependent ion channels participate in intracellular signalling pathways. Channels
      can directly activate enzymes linked to cellular signalling pathways, serve as
      cell adhesion molecules or components of the cytoskeleton, and their activity can
      alter the expression of specific genes. Here, I review these findings and discuss
      the extent to which the molecular mechanisms of such signalling are understood.

PMID- 16988653
TI  - Morphogen to mitogen: the multiple roles of hedgehog signalling in vertebrate
      neural development.
AB  - Sonic hedgehog has received an enormous amount of attention since its role as a
      morphogen that directs ventral patterning in the spinal cord was discovered a
      decade ago. Since that time, a bewildering array of information has been
      generated concerning both the components of the hedgehog signalling pathway and
      the remarkable number of contexts in which it functions. Nowhere is this more
      evident than in the nervous system, where hedgehog signalling has been implicated
      in events as disparate as axonal guidance and stem cell maintenance. Here we
      review our present knowledge of the hedgehog signalling pathway and speculate
      about areas in which further insights into this versatile pathway might be
      forthcoming.

PMID- 16988654
TI  - Histone deacetylase inhibitors as therapeutics for polyglutamine disorders.
AB  - During the past 5 years, gene expression studies in cell culture, animal models
      and in the brains of patients have shown that the perturbation of transcription
      frequently results in neuronal dysfunction in polyglutamine repeat diseases such
      as Huntington's disease. Histone deacetylases act as repressors of transcription
      through interactions with co-repressor complexes, which leads to chromatin
      remodelling. Aberrant interactions between polyglutamine proteins and regulators
      of transcription could be one mechanism by which transcriptional dysregulation
      occurs. Here, we discuss the potential therapeutic pathways through which histone
      deacetylase inhibitors might act to correct the aberrant transcription observed
      in Huntington's disease and other polyglutamine repeat diseases.

PMID- 16988655
TI  - Cancer pain and its impact on diagnosis, survival and quality of life.
AB  - Cancer pain significantly affects the diagnosis, quality of life and survival of
      patients with cancer. During the past decade, preclinical and clinical data has
      begun to provide insight into the mechanisms that drive and mask cancer pain and
      the mechanisms by which anti-neoplastic agents induce peripheral neuropathy.
      Developing a mechanism-based understanding and mechanism-based therapies to treat
      cancer-associated pain and sensory neuropathy, and incorporating these into
      mainstream cancer research and therapy, will be crucial to improving the quality
      of life and survival of patients with cancer.

PMID- 16988656
TI  - Brain plasticity and mental processes: Cajal again.
AB  - The year 2006 marks the 100th anniversary of the first Nobel Prize for Physiology
      or Medicine for studies in the field of the Neurosciences jointly awarded to
      Camillo Golgi and Santiago Ramon y Cajal for their key contributions to the study
      of the nervous system. This award represented the beginning of the modern era of
      neuroscience. Using the Golgi method, Cajal made fundamental, but often
      unappreciated, contributions to the study of the relationship between brain
      plasticity and mental processes. Here, I focus on some of these early experiments
      and how they continue to influence studies of brain plasticity.

PMID- 16988657
TI  - Intermediate phenotypes and genetic mechanisms of psychiatric disorders.
AB  - Genes are major contributors to many psychiatric diseases, but their mechanisms
      of action have long seemed elusive. The intermediate phenotype concept represents
      a strategy for characterizing the neural systems affected by risk gene variants
      to elucidate quantitative, mechanistic aspects of brain function implicated in
      psychiatric disease. Using imaging genetics as an example, we illustrate recent
      advances, challenges and implications of linking genes to structural and
      functional variation in brain systems related to cognition and emotion.

PMID- 16988658
TI  - Direct observation of individual RecA filaments assembling on single DNA
      molecules.
AB  - Escherichia coli RecA is essential for the repair of DNA double-strand breaks by
      homologous recombination. Repair requires the formation of a RecA nucleoprotein
      filament. Previous studies have indicated a mechanism of filament assembly
      whereby slow nucleation of RecA protein on DNA is followed by rapid growth.
      However, many aspects of this process remain unclear, including the rates of
      nucleation and growth and the involvement of ATP hydrolysis, largely because
      visualization at the single-filament level is lacking. Here we report the direct
      observation of filament assembly on individual double-stranded DNA molecules
      using fluorescently modified RecA. The nucleoprotein filaments saturate the DNA
      and extend it approximately 1.6-fold. At early time points, discrete RecA
      clusters are seen, permitting analysis of single-filament growth from individual
      nuclei. Formation of nascent RecA filaments is independent of ATP hydrolysis but
      is dependent on the type of nucleotide cofactor and the RecA concentration,
      suggesting that nucleation involves binding of approximately 4-5 ATP-RecA
      monomers to DNA. Individual RecA filaments grow at rates of 3-10 nm s(-1). Growth
      is bidirectional and, in contrast to nucleation, independent of nucleotide
      cofactor, suggesting addition of approximately 2-7 monomers s(-1). These results
      are in accord with extensive genetic and biochemical studies, and indicate that
      assembly in vivo is controlled at the nucleation step. We anticipate that our
      approach and conclusions can be extended to the related eukaryotic counterpart,
      Rad51 (see ref.), and to regulation by assembly mediators.

PMID- 16988659
TI  - Gene therapy: X-SCID transgene leukaemogenicity.
AB  - Gene therapy has been remarkably effective for the immunological reconstitution
      of patients with severe combined immune deficiency, but the occurrence of
      leukaemia in a few patients has stimulated debate about the safety of the
      procedure and the mechanisms of leukaemogenesis. Woods et al. forced high
      expression of the corrective therapeutic gene IL2RG, which encodes the gamma
      chain of the interleukin-2 receptor, in a mouse model of the disease and found
      that tumours appeared in a proportion of cases. Here we show that transgenic
      IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue
      that the interpretation of this observation with respect to human trials is
      overstated.

PMID- 16988660
TI  - Gene therapy: is IL2RG oncogenic in T-cell development?
AB  - The gene IL2RG encodes the gamma-chain of the interleukin-2 receptor and is
      mutated in patients with X-linked severe combined immune deficiency (X-SCID).
      Woods et al. report the development of thymus tumours in a mouse model of X-SCID
      after correction by lentiviral overexpression of IL2RG and claim that these were
      caused by IL2RG itself. Here we find that retroviral overexpression of IL2RG in
      human CD34+ cells has no effect on T-cell development, whereas overexpression of
      the T-cell acute lymphoblastic leukaemia (T-ALL) oncogene LMO2 leads to severe
      abnormalities. Retroviral expression of IL2RG may therefore not be directly
      oncogenic--rather, the restoration of normal signalling by the interleukin-7
      receptor to X-SCID precursor cells allows progression of T-cell development to
      stages that are permissive for the pro-leukaemic effects of ectopic LMO2.

PMID- 16988666
TI  - An ailing agency.

PMID- 16988665
TI  - Libya's travesty.

PMID- 16988669
TI  - Health agency backs use of DDT against malaria.

PMID- 16988670
TI  - Claims of brain drain follow CDC reshuffle.

PMID- 16988671
TI  - Agency accused of 'illusion of integrity'.

PMID- 16988672
TI  - Mystery surrounds lab death.

PMID- 16988673
TI  - Lawyers call for science to clear AIDS nurses in Libya.

PMID- 16988676
TI  - Snapshot: idol scans.

PMID- 16988675
TI  - That's no laser, it's a particle accelerator.

PMID- 16988678
TI  - Sequencers step up to the speed challenge.

PMID- 16988681
TI  - Medicine: sleep it off.

PMID- 16988682
TI  - Environmental science: a testing experience.

PMID- 16988683
TI  - Palaeoanthropology: the history man.

PMID- 16988684
TI  - Taking time to savour the rewards of slow science.

PMID- 16988685
TI  - Iran's progress towards nuclear capability is no joke.

PMID- 16988687
TI  - Iran: support for science does not outweigh crimes.

PMID- 16988686
TI  - Iran is sixth, not second, in Middle East publication list.

PMID- 16988688
TI  - Freedom of the mind got Nature banned by the Nazis.

PMID- 16988694
TI  - Climate change: Greenland's ice on the scales.

PMID- 16988695
TI  - Palaeoanthropology: a precious little bundle.

PMID- 16988697
TI  - Mathematical physics: search research.

PMID- 16988698
TI  - HIV: tired T cells turn around.

PMID- 16988699
TI  - Astronomy: champagne supernova.

PMID- 16988700
TI  - Stem cells: a new route to rejuvenation.

PMID- 16988701
TI  - Chemical biology: a sweet exchange.

PMID- 16988702
TI  - Induction of an illusory shadow person.
AB  - Stimulation of a site on the brain's left hemisphere prompts the creepy feeling
      that somebody is close by. The strange sensation that somebody is nearby when no
      one is actually present has been described by psychiatric and neurological
      patients, as well as by healthy subjects, but it is not understood how the
      illusion is triggered by the brain. Here we describe the repeated induction of
      this sensation in a patient who was undergoing presurgical evaluation for
      epilepsy treatment, as a result of focal electrical stimulation of the left
      temporoparietal junction: the illusory person closely 'shadowed' changes in the
      patient's body position and posture. These perceptions may have been due to a
      disturbance in the multisensory processing of body and self at the
      temporoparietal junction.

PMID- 16988703
TI  - Central nervous system control of food intake and body weight.
AB  - The capacity to adjust food intake in response to changing energy requirements is
      essential for survival. Recent progress has provided an insight into the
      molecular, cellular and behavioural mechanisms that link changes of body fat
      stores to adaptive adjustments of feeding behaviour. The physiological importance
      of this homeostatic control system is highlighted by the severe obesity that
      results from dysfunction of any of several of its key components. This new
      information provides a biological context within which to consider the global
      obesity epidemic and identifies numerous potential avenues for therapeutic
      intervention and future research.

PMID- 16988704
TI  - A juvenile early hominin skeleton from Dikika, Ethiopia.
AB  - Understanding changes in ontogenetic development is central to the study of human
      evolution. With the exception of Neanderthals, the growth patterns of fossil
      hominins have not been studied comprehensively because the fossil record
      currently lacks specimens that document both cranial and postcranial development
      at young ontogenetic stages. Here we describe a well-preserved 3.3-million-year
      old juvenile partial skeleton of Australopithecus afarensis discovered in the
      Dikika research area of Ethiopia. The skull of the approximately three-year-old
      presumed female shows that most features diagnostic of the species are evident
      even at this early stage of development. The find includes many previously
      unknown skeletal elements from the Pliocene hominin record, including a hyoid
      bone that has a typical African ape morphology. The foot and other evidence from
      the lower limb provide clear evidence for bipedal locomotion, but the gorilla
      like scapula and long and curved manual phalanges raise new questions about the
      importance of arboreal behaviour in the A. afarensis locomotor repertoire.

PMID- 16988705
TI  - The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf
      star.
AB  - The accelerating expansion of the Universe, and the need for dark energy, were
      inferred from observations of type Ia supernovae. There is a consensus that type
      Ia supernovae are thermonuclear explosions that destroy carbon-oxygen white dwarf
      stars that have accreted matter from a companion star, although the nature of
      this companion remains uncertain. These supernovae are thought to be reliable
      distance indicators because they have a standard amount of fuel and a uniform
      trigger: they are predicted to explode when the mass of the white dwarf nears the
      Chandrasekhar mass of 1.4 solar masses (M(o)). Here we show that the high
      redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low
      kinetic energy that both imply a super-Chandrasekhar-mass progenitor. Super
      Chandrasekhar-mass supernovae should occur preferentially in a young stellar
      population, so this may provide an explanation for the observed trend that
      overluminous type Ia supernovae occur only in 'young' environments. As this
      supernova does not obey the relations that allow type Ia supernovae to be
      calibrated as standard candles, and as no counterparts have been found at low
      redshift, future cosmology studies will have to consider possible contamination
      from such events.

PMID- 16988706
TI  - Spontaneous symmetry breaking in a quenched ferromagnetic spinor Bose-Einstein
      condensate.
AB  - A central goal in condensed matter and modern atomic physics is the exploration
      of quantum phases of matter--in particular, how the universal characteristics of
      zero-temperature quantum phase transitions differ from those established for
      thermal phase transitions at non-zero temperature. Compared to conventional
      condensed matter systems, atomic gases provide a unique opportunity to explore
      quantum dynamics far from equilibrium. For example, gaseous spinor Bose-Einstein
      condensates (whose atoms have non-zero internal angular momentum) are quantum
      fluids that simultaneously realize superfluidity and magnetism, both of which are
      associated with symmetry breaking. Here we explore spontaneous symmetry breaking
      in 87Rb spinor condensates, rapidly quenched across a quantum phase transition to
      a ferromagnetic state. We observe the formation of spin textures, ferromagnetic
      domains and domain walls, and demonstrate phase-sensitive in situ detection of
      spin vortices. The latter are topological defects resulting from the symmetry
      breaking, containing non-zero spin current but no net mass current.

PMID- 16988707
TI  - 'Designer atoms' for quantum metrology.
AB  - Entanglement is recognized as a key resource for quantum computation and quantum
      cryptography. For quantum metrology, the use of entangled states has been
      discussed and demonstrated as a means of improving the signal-to-noise ratio. In
      addition, entangled states have been used in experiments for efficient quantum
      state detection and for the measurement of scattering lengths. In quantum
      information processing, manipulation of individual quantum bits allows for the
      tailored design of specific states that are insensitive to the detrimental
      influences of an environment. Such 'decoherence-free subspaces' (ref. 10) protect
      quantum information and yield significantly enhanced coherence times. Here we use
      a decoherence-free subspace with specifically designed entangled states to
      demonstrate precision spectroscopy of a pair of trapped Ca+ ions; we obtain the
      electric quadrupole moment, which is of use for frequency standard applications.
      We find that entangled states are not only useful for enhancing the signal-to
      noise ratio in frequency measurements--a suitably designed pair of atoms also
      allows clock measurements in the presence of strong technical noise. Our
      technique makes explicit use of non-locality as an entanglement property and
      provides an approach for 'designed' quantum metrology.

PMID- 16988708
TI  - A guest-free germanium clathrate.
AB  - The challenges associated with synthesizing expanded semiconductor frameworks
      with cage-like crystal structures continue to be of interest. Filled low-density
      germanium and silicon framework structures have distinct properties that address
      important issues in thermoelectric phonon glass-electron crystals,
      superconductivity and the possibility of Kondo insulators. Interest in empty
      framework structures of silicon and germanium is motivated by their predicted
      wide optical bandgaps of the same magnitude as quantum dots and porous silicon,
      making them and their alloys promising materials for silicon-based optoelectronic
      devices. Although almost-empty Na(1-x)Si136 has already been reported, the
      synthesis of guest-free germanium clathrate has so far been unsuccessful. Here we
      report the high-yield synthesis and characteristics of germanium with the empty
      clathrate-II structure through the oxidation of Zintl anions in ionic liquids
      under ambient conditions. The approach demonstrates the potential of ionic
      liquids as media for the reactions of polar intermetallic phases.

PMID- 16988709
TI  - The cause of the fragile relationship between the Pacific El Nino and the
      Atlantic Nino.
AB  - El Nino, the most prominent climate fluctuation at seasonal-to-interannual
      timescales, has long been known to have a remote impact on climate variability in
      the tropical Atlantic Ocean, but a robust influence is found only in the northern
      tropical Atlantic region. Fluctuations in the equatorial Atlantic are dominated
      by the Atlantic Nino, a phenomenon analogous to El Nino, characterized by
      irregular episodes of anomalous warming during the boreal summer. The Atlantic
      Nino strongly affects seasonal climate prediction in African countries bordering
      the Gulf of Guinea. The relationship between El Nino and the Atlantic Nino is
      ambiguous and inconsistent. Here we combine observational and modelling analysis
      to show that the fragile relationship is a result of destructive interference
      between atmospheric and oceanic processes in response to El Nino. The net effect
      of El Nino on the Atlantic Nino depends not only on the atmospheric response that
      propagates the El Nino signal to the tropical Atlantic, but also on a dynamic
      ocean-atmosphere interaction in the equatorial Atlantic that works against the
      atmospheric response. These results emphasize the importance of having an
      improved ocean-observing system in the tropical Atlantic, because our ability to
      predict the Atlantic Nino will depend not only on our knowledge of conditions in
      the tropical Pacific, but also on an accurate estimate of the state of the upper
      ocean in the equatorial Atlantic.

PMID- 16988710
TI  - Acceleration of Greenland ice mass loss in spring 2004.
AB  - In 2001 the Intergovernmental Panel on Climate Change projected the contribution
      to sea level rise from the Greenland ice sheet to be between -0.02 and +0.09 m
      from 1990 to 2100 (ref. 1). However, recent work has suggested that the ice sheet
      responds more quickly to climate perturbations than previously thought,
      particularly near the coast. Here we use a satellite gravity survey by the
      Gravity Recovery and Climate Experiment (GRACE) conducted from April 2002 to
      April 2006 to provide an independent estimate of the contribution of Greenland
      ice mass loss to sea level change. We detect an ice mass loss of 248 +/- 36 km3
      yr(-1), equivalent to a global sea level rise of 0.5 +/- 0.1 mm yr(-1). The rate
      of ice loss increased by 250 per cent between the periods April 2002 to April
      2004 and May 2004 to April 2006, almost entirely due to accelerated rates of ice
      loss in southern Greenland; the rate of mass loss in north Greenland was almost
      constant. Continued monitoring will be needed to identify any future changes in
      the rate of ice loss in Greenland.

PMID- 16988711
TI  - Geological and palaeontological context of a Pliocene juvenile hominin at Dikika,
      Ethiopia.
AB  - Since 1999, the Dikika Research Project (DRP; initiated by Z.A.) has conducted
      surveys and excavations in badlands that expose Pliocene and Pleistocene
      sediments south of the Awash River in Ethiopia, between surrounding hominin
      localities at Hadar, Gona and the Middle Awash region. Here we report our
      geological mapping and stratigraphic measurement of the DRP area, and the context
      of a remarkably well-preserved skeleton of the earliest known juvenile hominin at
      the Dikika DIK-1 locality. Our mapping of the DRP area permits a complete
      definition of the hominin-bearing Hadar Formation and provides a cohesive
      structural and tectonic framework defining its relationships to adjacent strata.
      Our findings reveal the basin-scale tectonic, depositional and
      palaeoenvironmental history of the area, as well as a clear taphonomic and
      palaeontological context for the juvenile hominin. Such data are crucial for
      understanding the environmental context of human evolution, and can be integrated
      into larger-scale tectonic and palaeoenvironmental studies. Our basin-scale
      approach to palaeoenvironments provides a means to elucidate the complex
      geological history occurring at the scale of temporally and geographically
      controlled fossil point localities, which occur within the rich tectonic and
      depositional history of the Awash Valley.

PMID- 16988712
TI  - A common progenitor for haematopoietic and endothelial lineages in the zebrafish
      gastrula.
AB  - It has been proposed that haematopoietic and endothelial cells share a common
      progenitor, termed the haemangioblast. This idea was initially conceived as a
      result of the observation that these two cell types develop in close proximity to
      each other within the embryo. Support for this hypothesis was provided by studies
      on single-cell-derived colonies that can produce both haematopoietic and
      endothelial cells in vitro. Although these data point towards the existence of a
      common progenitor for these two lineages, the presence of a bipotential
      progenitor cell has yet to be demonstrated in vivo. Through the construction of
      single-cell-resolution fate maps of the zebrafish late blastula and gastrula, we
      demonstrate that individual cells can give rise to both haematopoietic and
      endothelial cells. These bipotential progenitors arise along the entire extent of
      the ventral mesoderm and contribute solely to haematopoietic and endothelial
      cells. We also find that only a subset of haematopoietic and endothelial cells
      arise from haemangioblasts. The endothelial descendants of the haemangioblasts
      all clustered in a specific region of the axial vessels regardless of the
      location of their progenitors. Our results provide in vivo evidence supporting
      the existence of the haemangioblast and reveal distinct features of this cell
      population.

PMID- 16988713
TI  - Topical drug rescue strategy and skin protection based on the role of Mc1r in UV
      induced tanning.
AB  - Ultraviolet-light (UV)-induced tanning is defective in numerous 'fair-skinned'
      individuals, many of whom contain functional disruption of the melanocortin 1
      receptor (MC1R). Although this suggested a critical role for the MC1R ligand
      melanocyte stimulating hormone (MSH) in this response, a genetically controlled
      system has been lacking in which to determine the precise role of MSH-MC1R. Here
      we show that ultraviolet light potently induces expression of MSH in
      keratinocytes, but fails to stimulate pigmentation in the absence of functional
      MC1R in red/blonde-haired Mc1r(e/e) mice. However, pigmentation could be rescued
      by topical application of the cyclic AMP agonist forskolin, without the need for
      ultraviolet light, demonstrating that the pigmentation machinery is available
      despite the absence of functional MC1R. This chemically induced pigmentation was
      protective against ultraviolet-light-induced cutaneous DNA damage and
      tumorigenesis when tested in the cancer-prone, xeroderma-pigmentosum
      complementation-group-C-deficient genetic background. These data emphasize the
      essential role of intercellular MSH signalling in the tanning response, and
      suggest a clinical strategy for topical small-molecule manipulation of
      pigmentation.

PMID- 16988714
TI  - Calcineurin/NFAT signalling regulates pancreatic beta-cell growth and function.
AB  - The growth and function of organs such as pancreatic islets adapt to meet
      physiological challenges and maintain metabolic balance, but the mechanisms
      controlling these facultative responses are unclear. Diabetes in patients treated
      with calcineurin inhibitors such as cyclosporin A indicates that
      calcineurin/nuclear factor of activated T-cells (NFAT) signalling might control
      adaptive islet responses, but the roles of this pathway in beta-cells in vivo are
      not understood. Here we show that mice with a beta-cell-specific deletion of the
      calcineurin phosphatase regulatory subunit, calcineurin b1 (Cnb1), develop age
      dependent diabetes characterized by decreased beta-cell proliferation and mass,
      reduced pancreatic insulin content and hypoinsulinaemia. Moreover, beta-cells
      lacking Cnb1 have a reduced expression of established regulators of beta-cell
      proliferation. Conditional expression of active NFATc1 in Cnb1-deficient beta
      cells rescues these defects and prevents diabetes. In normal adult beta-cells,
      conditional NFAT activation promotes the expression of cell-cycle regulators and
      increases beta-cell proliferation and mass, resulting in hyperinsulinaemia.
      Conditional NFAT activation also induces the expression of genes critical for
      beta-cell endocrine function, including all six genes mutated in hereditary forms
      of monogenic type 2 diabetes. Thus, calcineurin/NFAT signalling regulates
      multiple factors that control growth and hallmark beta-cell functions, revealing
      unique models for the pathogenesis and therapy of diabetes.

PMID- 16988717
TI  - Restorative effect of insulin-like growth factor-I gene therapy in the
      hypothalamus of senile rats with dopaminergic dysfunction.
AB  - Insulin-like growth factor-I (IGF-I) is emerging as a powerful neuroprotective
      molecule that is strongly induced in the central nervous system after different
      insults. We constructed a recombinant adenoviral vector (RAd-IGFI) harboring the
      gene for rat IGF-I and used it to implement IGF-I gene therapy in the
      hypothalamus of senile female rats, which display hypothalamic dopaminergic (DA)
      neurodegeneration and as a consequence, chronic hyperprolactinemia. Restorative
      IGF-I gene therapy was implemented in young (5 months) and senile (28 months)
      female rats, which received a single intrahypothalamic injection of 3 x 10(9)
      plaque-forming units of RAd-betagal (a control adenoviral vector expressing beta
      galactosidase) or RAd-IGFI and were killed 17 days post-injection. In the young
      animals, neither vector modified serum prolactin levels, but in the RAd-IGFI
      injected senile rats a nearly full reversion of their hyperprolactinemic status
      was recorded. Morphometric analysis revealed a significant increase in the total
      number of tyrosine hydroxylase-positive cells in the hypothalamus of experimental
      as compared with control senile animals (5874+/-486 and 3390+/-498,
      respectively). Our results indicate that IGF-I gene therapy in senile female rats
      is highly effective for restoring their hypothalamic DA dysfunction and thus
      reversing their chronic hyperprolactinemia.

PMID- 16988718
TI  - Optimization of cutaneous electrically mediated plasmid DNA delivery using novel
      electrode.
AB  - The easy accessibility of skin makes it an excellent target for gene transfer
      protocols. To take advantage of skin as a target for gene transfer, it is
      important to establish an efficient and reproducible delivery system.
      Electroporation is an established technique for enhancing plasmid delivery to
      many tissues in vivo. A critical component of this technique is the electrode
      configuration. Electroporation parameters were optimized for transgene expression
      with minimal tissue damage with a novel electrode. The highest transgene
      expression and efficiency of individual cell transformation with minimal damage
      was produced with eight 150 ms pulses at field strength of 100 V/cm. This
      electrode design offers the potential for easier and more reproducible
      electrically mediated cutaneous plasmid delivery than the simple electrodes
      currently commercially available. This electrode can be a valuable tool in
      determining the applicability of electrically mediated cutaneous gene transfer.

PMID- 16988719
TI  - Structural impact of hydrodynamic injection on mouse liver.
AB  - The impact of hydrodynamic injection on liver structure was evaluated in mice
      using various microscopic techniques. Upon hydrodynamic injection of
      approximately 9% of body weight by volume, the liver rapidly expanded, reaching
      maximal size at the end of the injection and returned to its original size in 30
      min. Histological analysis revealed a swollen appearance in the peri-central
      region of the liver where delivery of genes and fluorescence-labeled markers was
      observed. Scanning and transmission electron microscopy showed enlargement and
      rupture of endothelium that in about 24-48 h regains its morphology and normal
      function as a barrier against infection by adenovirus viral particles. At the
      cellular level in hydrodynamically treated animals, four types of hepatocytes
      were seen: cells with normal appearance; cells with enriched vesicles in the
      cytoplasm; cells with lightly stained cytosol; and cells with significant
      dilution of the cytoplasm. In addition, red blood cells and platelets were
      observed in the space of Disse and even inside hepatocytes. Vesicle formation is
      triggered by hydrodynamic injection and resembles the process of
      macropinocytosis. These results, whereas confirming the physical nature of
      hydrodynamic delivery, are important for a better understanding of this efficient
      method for intrahepatic gene and small interfering RNA delivery.

PMID- 16988721
TI  - The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5
      inhibitor therapy.
AB  - Differences in clinical pharmacology of the currently marketed phosphodiesterase
      (PDE)5 inhibitors sildenafil, vardenafil and tadalafil are largely determined by
      their pharmacokinetic (PK) properties and their PDE5 inhibitory activity profile.
      This review outlines the basic concepts of pharmacokinetics and pharmacokinetic
      pharmacodynamic (PK/PD) relationships and their relevance to dose selection and
      applied pharmacotherapy. It is followed by a detailed comparative discussion on
      the pharmacokinetics and exposure-response relationship of the currently
      available PDE5 inhibitors, including known drug-drug interactions and dosage
      adjustments in special populations. The review is aimed at providing a critical
      assessment of the pharmacokinetics of PDE5 inhibitors, which may assist
      clinicians in tailoring drug and/or treatment regimens to the unique needs of
      each individual patient with erectile dysfunction.

PMID- 16988724
TI  - Free article for sale: 11,000 US dollars--what is free public access worth?

PMID- 16988722
TI  - Predictors of nutritive sucking in preterm infants.
AB  - OBJECTIVE: The purposes of this analysis were to determine how select
      characteristics of nutritive sucking (number of sucks, sucks/burst, and
      sucks/minute) change over time and to examine the effect of select factors
      (morbidity, maturity, prefeeding behavior state, and feeding experience) on those
      changes. STUDY DESIGN: A longitudinal, non-experimental study was conducted in a
      Level 3 neonatal intensive care unit using a convenience sample of 88 preterm
      infants. Statistical analyses were performed using a repeated-measures mixed
      model in SAS. RESULTS: Sucking activity (number of sucks, sucks/burst, and
      sucks/minute) was predicted by morbidity, maturity, feeding experience and
      prefeeding behavior state. Experience at oral feeding had the greatest effect on
      changes in the number of sucks, suck/burst and sucks/minute. CONCLUSION:
      Experience at feeding may result in more rapid maturation of sucking
      characteristics.

PMID- 16988725
TI  - Calciphylaxis.

PMID- 16988726
TI  - Tetany during bicarbonate loading test.

PMID- 16988727
TI  - Treatment of the primary hyperoxalurias: a new chapter.
AB  - Despite advances in the enzymology, molecular genetics, and clinical knowledge of
      the primary hyperoxalurias, few treatments are available. Oxalobacter formigenes
      is a promising new therapy with potential to induce secretion of oxalate into the
      intestinal lumen, where it can be degraded by the bacteria.

PMID- 16988728
TI  - Specific molecular targeting of renal injury in obstructive nephropathy.
AB  - Progression of most renal disease involves tubulointerstitial injury,
      characterized by tubular atrophy, inflammatory cell infiltration, and
      interstitial fibrosis. Transforming growth factor-beta1 is central in this
      process. As reported by Moon et al., molecular targeting of the transforming
      growth factor-beta1 signaling pathway can markedly suppress renal injury
      resulting from unilateral ureteral obstruction, an established model of
      obstructive nephropathy. Specific kinase inhibitors are promising therapeutic
      agents to slow or attenuate progressive renal fibrosis.

PMID- 16988729
TI  - Do we know the optimal dose for renal replacement therapy in the intensive care
      unit?
AB  - Increasing the dose of renal replacement therapy might increase survival in
      critically ill patients with acute renal failure. For continuous renal
      replacement therapy (CRRT), a single-center study suggests that increasing urea
      clearance from 20 ml/kg/h to 35-45 ml/kg/h might increase short-term survival. A
      further single-center study has now confirmed that the dose of CRRT might be a
      determinant of outcome. This issue is now being addressed by two large
      multicenter randomized controlled trials in the United States (the ATN study) and
      Australia and New Zealand (the RENAL study). The results of these two studies
      should be available in 2008. Before making any major changes to practice, it
      seems prudent to wait for the publication of the findings of these two pivotal
      trials.

PMID- 16988731
TI  - Is there a link between inflammation, plasma resistin levels, and protein
      malnutrition in hemodialysis patients?

PMID- 16988732
TI  - Resistin and GFR.

PMID- 16988736
TI  - Downloadable computer models for maintenance but not acute renal replacement
      therapy.

PMID- 16988733
TI  - Enlightenment on liver lanthanum exposure.

PMID- 16988738
TI  - Hardy-Weinberg equilibrium and control subjects.

PMID- 16988740
TI  - Ultrasonography and graft patency.

PMID- 16988741
TI  - ACE inhibitor use and the long-term risk of renal failure in diabetics.

PMID- 16988743
TI  - ACE inhibitor use and the increased long-term risk of renal failure in diabetes.

PMID- 16988744
TI  - Angiotensin-converting enzyme inhibitors and renal failure in diabetes.

PMID- 16988746
TI  - Late-onset renal failure from RAAS blockade.

PMID- 16988747
TI  - Quantitative analysis of the dysnatremias.

PMID- 16988749
TI  - Lanthanum data in perspective.

PMID- 16988752
TI  - Hypertensive nephrosclerosis.

PMID- 16988753
TI  - Between-country variation in the utilization of antihypertensive agents:
      Guidelines and clinical practice.
AB  - Variation in antihypertensive drug utilization and guideline preferences between
      six European countries (Denmark, Finland, Germany, Norway, Sweden, the
      Netherlands) was investigated. Our objectives were to compare between-country
      variability in utilization per class of antihypertensive agents and to assess
      guideline preferences in relation to actual use. Antihypertensive consumption
      data (2003) was retrieved. We classified antihypertensive agents using ATC-codes:
      C02CA - alpha-blockers (AB), C03A - thiazide diuretics (TD), C07AB - beta
      blockers (BB), C08CA - dihydropyridine calcium antagonists (CA), C09A/C09BA/C09BB
      - ACE-inhibitors+combinations (AI) and C09C/C09D - angiotensin II receptor
      blockers+combinations (AT2). For each class, DDDs/1000 persons/day and share (%)
      of total antihypertensive utilization was calculated. Per class, relative
      standard deviations (RSD) across countries were computed. Current hypertension
      guidelines were requested from national medical associations. Total
      antihypertensive utilization varied considerably, ranging from 152.4
      (Netherlands) to 246.9 (Germany) DDDs/1000 persons/day. RSD was highest for TD
      (106.2%) and AB (93.6%). Where guidelines advocated TDs (Norway and Netherlands),
      TD utilization was below (Norway) or just above (Netherlands) median TD use.
      Guidelines recommended TD (Norway and Netherlands), TD/BB/AI (Finland, German
      Physicians Association) or TD/BB/CA/AI/AT2 (Denmark, German Hypertension
      Society), Sweden had no recent national guideline. In conclusion,
      antihypertensive utilization patterns varied largely across these six countries,
      in absolute and relative terms. Furthermore, guidelines seem disconnected from
      clinical practice in some countries, and none of the guidelines discuss current
      utilization. Whether this reflects a need for change in prescribing or re
      evaluation of guidelines warrants further research.

PMID- 16988754
TI  - Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in
      patients with hypertension and other cardiovascular risk factors.
AB  - We aimed to compare the effects of two different vasodilating principles,
      angiotensin II-receptor blockade and calcium channel blockade, on peripheral
      insulin-mediated glucose uptake in patients with hypertension and other
      cardiovascular risk factors. Twenty-one hypertensive patients (11 women and 10
      men) with mean age 58.6 years (range 46-75 years), body mass index 29.2 +/- 1.0
      kg/m(2) and blood pressure 160 +/- 3/96 +/- 2 mm Hg entered a 4-week run-in
      period with open-label amlodipine 5 mg. Thereafter they were randomized double
      blindly to additional treatment with amlodipine 5 mg or losartan 100 mg. After 8
      weeks of treatment, all patients underwent clinical examination and laboratory
      testing, and 17 of them underwent a hyperinsulinaemic isoglycaemic glucose clamp.
      After a 4-week open-label wash-out phase, the participants crossed over to the
      opposite treatment regimen and final examinations with hyperinsulinaemic
      isoglycaemic glucose clamp after another 8 weeks. Blood pressure was lowered to
      the same level in both treatment periods. The glucose disposal rate was
      significantly higher after treatment with losartan 100 mg + amlodipine 5 mg
      compared to amlodipine 10 mg (4.9 +/- 0.4 vs 4.2 +/- 0.5 mg/kg/min, P = 0.039).
      Thus our data suggest that angiotensin II-receptor blockade with losartan
      improves glucose metabolism at the cellular level beyond what can be expected by
      the vasodilatation and blood pressure reduction alone.

PMID- 16988756
TI  - Duplicate gallbladder: an unusual case report.
AB  - Duplication of the gallbladder, a rare congenital anomaly, is important in
      clinical practice as it may cause some clinical, surgical and diagnostic
      problems. In this report we present a case of duplicated gallbladder diagnosed
      serendipitously in a 63-year-old male patient who had previously undergone
      successful laparoscopic cholecystectomy (confirmed histologically) approximately
      a year before for gallstones. The patient was re-admitted with obstructive
      jaundice. An abdominal computed tomography scan and magnetic resonance
      cholangiogram both revealed the presence of a gallbladder, which was thereafter
      removed at surgery undertaken to palliate the jaundice.

PMID- 16988757
TI  - Diversity of 16S rRNA gene, ITS region and aclB gene of the Aquificales.
AB  - The Aquificales are prevalent members of the microbial communities inhabiting
      many marine and terrestrial hydrothermal systems. Numerous new strains were
      obtained from deep-sea and terrestrial hydrothermal systems. In order to resolve
      the phylogenetic relationships within this group, three different phylogenetic
      datasets were used, namely the 16S rRNA gene, the intergenic transcribed spacer
      region between the 16S rRNA and 23S rRNA genes (ITS) and the gene coding for the
      ATP citrate lyase (aclB), a key enzyme in the reductive TCA cycle. The data were
      analyzed using neighbor-joining, parsimony and maximum likelihood. The resulting
      phylogenies appeared to be consistent between the three markers. The three genes
      confirmed the presence of isolates that merit further characterization and
      descriptions as new species and perhaps even new genera. The detailed
      phylogenetic interrelationships of these isolates are described here.

PMID- 16988758
TI  - Thermincola ferriacetica sp. nov., a new anaerobic, thermophilic, facultatively
      chemolithoautotrophic bacterium capable of dissimilatory Fe(III) reduction.
AB  - A moderately thermophilic, sporeforming bacterium able to reduce amorphous
      Fe(III)-hydroxide was isolated from ferric deposits of a terrestrial hydrothermal
      spring, Kunashir Island (Kurils), and designated as strain Z-0001. Cells of
      strain Z-0001 were straight, Gram-positive rods, slowly motile. Strain Z-0001 was
      found to be an obligate anaerobe. It grew in the temperature range from 45 to 70
      degrees C with an optimum at 57-60 degrees C, in a pH range from 5.9 to 8.0 with
      an optimum at 7.0-7.2, and in NaCl concentration range 0-3.5% with an optimum at
      0%. Molecular hydrogen, acetate, peptone, yeast and beef extracts, glycogen,
      glycolate, pyruvate, betaine, choline, N-acetyl-D-glucosamine and casamino acids
      were used as energy substrates for growth in presence of Fe(III) as an electron
      acceptor. Sugars did not support growth. Magnetite, Mn(IV) and anthraquinone-2,6
      disulfonate served as the alternative electron acceptors, supporting the growth
      of isolate Z-0001 with acetate as electron donor. Formation of magnetite was
      observed when amorphous Fe(III) hydroxide was used as electron acceptor. Yeast
      extract, if added, stimulated growth, but was not required. Isolate Z-0001 was
      able to grow chemolithoautotrophicaly with molecular hydrogen as the only energy
      substrate, Fe(III) as electron acceptor and CO(2) as the carbon source. Isolate Z
      0001 was able to grow with 100% CO as the sole energy source, producing H(2) and
      CO(2), requiring the presence of 0.2 g l(-1) of acetate as the carbon source. The
      G+C content of strain Z-0001(T )DNA G+C was 47.8 mol%. Based on 16S rRNA sequence
      analyses strain Z-0001 fell into the cluster of family Peptococcaceae, within the
      low G+C content Gram-Positive bacteria, clustering with Thermincola
      carboxydophila (98% similarity). DNA-DNA hybridization with T. carboxydophila was
      27%. On the basis of physiological and phylogenetic data it is proposed that
      strain Z-0001(T) (=DSMZ 14005, VKM B-2307) should be placed in the genus
      Thermincola as a new species Thermincola ferriacetica sp. nov.

PMID- 16988759
TI  - Clinical features of nonalcoholic steatohepatitis in Japan: Evidence from the
      literature.
AB  - Metabolic syndrome, that is, obesity, hypertension, hyperlipidemia, and insulin
      resistance with hyperinsulinemia, is a new disease entity prevailing worldwide,
      and nonalcoholic steatohepatitis (NASH) is believed to be a hepatic expression of
      this syndrome. NASH is characterized by zone 3-dominant hepatic steatosis with
      ballooned hepatocytes and Mallory bodies, zone 3 pericellular and perivenular
      fibrosis with or without bridging fibrosis, and lobular inflammatory cell
      infiltration. Indeed, 90% of NASH has been revealed to be complicated by visceral
      obesity, and two-thirds of NASH patients fulfill the criteria of metabolic
      syndrome. Therefore, a variety of lifestyle-related diseases such as obesity,
      hypertension, hyperlipidemia, and diabetes mellitus may share the same
      background. NASH is most prevalent and well characterized in Caucasians; however,
      little is known about its occurrence in Asia-Oceania, because obesity has not
      been frequent in countries in these areas. Obesity is expected to become a
      serious social problem in Asia-Oceania in the next two decades, so we need to
      prevent a corresponding increase of NASH. For that purpose, we need to know much
      about not only NASH but also ourselves. To elucidate the status of NASH in Japan,
      recent progress in the study of NASH in Japan is reviewed in this article.

PMID- 16988760
TI  - Phenotype analysis by MUC2, MUC5AC, MUC6, and CD10 expression in Epstein-Barr
      virus-associated gastric carcinoma.
AB  - BACKGROUND: Gastric marker mucins (MUC5AC and MUC6) and intestinal marker
      molecules (MUC2 and CD10) have been used to determine the cell lineage of
      epithelial cell of gastric carcinoma (GC). METHODS: To clarify the
      characteristics of Epstein-Barr virus (EBV)-associated GC, 18 cases were
      immunohistochemically evaluated along with 56 cases of EBV-negative GC. RESULTS:
      MUC2 expression was lower in EBV-associated GC: immunostaining grades 0, 1, 2, 3,
      and 4 were observed in 10, 6, 1, 1, and 0 cases of EBV-associated GC,
      respectively, and in 18, 11, 15, 6, and 6 cases of EBV-negative GC, respectively
      (P = 0.013). CD10 positivity (grades 2-4) in EBV-associated GC was 6%,
      significantly lower than in EBV-negative GC (34%) (P = 0.030). When phenotypes of
      GC were categorized by the combined positivities of gastric markers (either
      MUC5AC or MUC6) and intestinal markers (either MUC2 or CD10), EBV-associated GC
      included primarily null (44%) and gastric (39%) types, but EBV-negative GC
      comprised null (7%), gastric (30%), intestinal (27%), and mixed (36%) types. The
      age of patients with gastric types was significantly younger for both EBV
      associated GC and EBV-negative GC cases. CONCLUSIONS: Neoplastic epithelial cells
      of EBV-associated GC did not express MUC2 or CD10, and most of them were
      categorized as null or gastric types. EBV infection may occur in the epithelial
      cells of null or gastric phenotypes, which may be devoid of transdifferentiation
      potential toward intestinal phenotypes.

PMID- 16988761
TI  - Corticotropin-releasing factor induces rectal hypersensitivity after repetitive
      painful rectal distention in healthy humans.
AB  - BACKGROUND: Rectal hypersensitivity induced by repetitive rectal distention (RRD)
      is reported to be a response specific to patients with irritable bowel syndrome
      (IBS), and is not observed in healthy controls. We evaluated the rectal pain
      threshold (PT) and determined whether intravenous corticotropin-releasing factor
      (CRF) induces rectal hypersensitivity after RRD in healthy humans, that is,
      whether it mimics the response observed in IBS patients. METHODS: A double-blind
      placebo-controlled study design (CRF or vehicle) was used. In the first
      experiment, PT (mmHg) induced by ramp distention was measured by a barostat. Then
      CRF (100 microg, n = 5) or vehicle (n = 6) was injected intravenously (iv)
      followed by RRD, consisting of phasic distentions with sensory tracking, which
      lasted until the subjects had complained of pain six times. After RRD, PT was
      measured again. In another experiment, PT was measured, and then CRF (n = 5) or
      vehicle (n = 5) was injected iv. After 45 min, ramp distention was again induced
      to determine PT. RESULTS: In the placebo group, PT was not modified by RRD
      (before RRD, 33.0 +/- 6.8; after RRD, 33.4 +/- 4.5), while it was significantly
      reduced in the CRF-treated group (before RRD, 32.9 +/- 9.0; after RRD, 26.1 +/-
      7.9, P < 0.05). On the other hand, CRF or vehicle without RRD did not alter PT
      (before iv-CRF, 35.2 +/- 4.2; after iv-CRF, 35.3 +/- 4.9; before iv-vehicle, 34.5
      +/- 7; after iv-vehicle, 35.5 +/- 6.8). CONCLUSIONS: These results indicate that
      CRF modifies rectal sensation in healthy humans and mimics an IBS-specific
      visceral response, suggesting the possible contribution of CRF to the
      pathogenesis of IBS.

PMID- 16988762
TI  - Review of the pathological results of 2660 appendicectomy specimens.
AB  - PURPOSE: Appendicitis is the most commonly performed emergency abdominal surgery.
      The appendix can also be the site of a variety of neoplasms and unusual
      inflammatory conditions. A retrospective review was performed to determine the
      pathological diagnoses in appendicectomy specimens. METHODS: This study is a
      retrospective analysis of 2660 appendicectomies performed from 1997 to 2003. The
      reports were analyzed for the following parameters: age-related incidence of
      acute appendicitis, seasonal variation in presentation, perforation rate, rate of
      negative and incidental appendicectomy, and the incidence of other pathologies
      encountered. RESULTS: Of the 2660 appendicectomy specimens, acute appendicitis
      was seen in 1718 patients (64.58%), with a peak in patients in their second
      decade (35.09% of cases of acute appendicitis). The perforation rate was 13.9%
      and was significantly higher in patients aged 70 years or more (P < 0.001). The
      negative appendicectomy rate was 28.8%, and was significantly higher in female
      patients (P < 0.001) and in the 11-30 year age group (P < 0.001). Other
      pathologies include carcinoid (0.52%), adenocarcinoma (0.39%), and mucinous
      cystadenoma (0.60%). CONCLUSIONS: The high rate of negative appendicectomy among
      female patients and the increased incidence of perforation in elderly patients
      reinforce the validity of the judicious use of laparoscopy in these populations.
      There are still a number of unusual histologies found in appendicectomy specimens
      supporting the continued use of routine histology.

PMID- 16988763
TI  - Negative regulation of intracellular hepatitis C virus replication by interferon
      regulatory factor 3.
AB  - BACKGROUND: Interferon regulatory factor (IRF)-3 plays an important role in
      initiating cellular interferon-stimulated gene-mediated antiviral responses. In
      the present study, we evaluated the effects of IRF-3 expression and activation on
      intracellular hepatitis C virus (HCV) replication using an HCV replicon system.
      METHODS: An HCV replicon was constructed that expressed a neomycin-selectable
      chimeric firefly luciferase reporter protein. A small interfering (si) RNA
      oligonucleotide directed against IRF-3 mRNA was designed and synthesized. A
      eukaryote expression plasmid vector was constructed that expressed IRF-3 mRNA
      under control of the cytomegalovirus early promoter/enhancer. To evaluate
      transcriptional activity of the interferon-stimulated genes, a reporter vector
      was used that expressed firefly luciferase under control of the interferon
      stimulated response element (ISRE). RESULTS: The baseline expression of IRF-3 did
      not significantly differ between cells with and without expression of the
      replicon. Transfection of an IRF-3 expression plasmid into the cells raised the
      ISRE-luciferase activities. The increase of ISRE activity was significantly more
      potent in the replicon-expressing cells than in cells without replicon
      expression. Concomitantly, the overexpression of IRF-3 suppressed HCV replication
      levels. In contrast, siRNA knockdown of IRF-3 suppressed ISRE activity by 38% +/-
      2%. Interestingly, the suppression of IRF-3 resulted in a significant increase of
      HCV replication, by up to twofold, depending on the IRF-3 suppression levels.
      CONCLUSIONS: IRF-3 negatively regulated intracellular HCV replication, and was
      partially activated in cells that expressed the HCV replicon. Thus, IRF-3 is a
      key molecule controlling HCV replication through modulation of host interferon
      gene responses.

PMID- 16988764
TI  - Dynamics of immature subsets of dendritic cells during antiviral therapy in HLA
      A24-positive chronic hepatitis C patients.
AB  - BACKGROUND: The cellular immune response is important in chronic hepatitis C
      (CHC). To better understand its mechanism, we examined dendritic cells (DCs) and
      hepatitis C virus (HCV)-specific cytotoxic T cells (CTLs), which are thought to
      contribute to liver injury and viral clearance. METHODS: CHC patients received 24
      weeks of interferon-alpha-based antiviral therapy. We analyzed time-sequential
      frequencies of peripheral DCs, classified as myeloid DCs (mDCs) or plasmacytoid
      DCs (pDCs), together with peptide major histocompatibility class I tetramers,
      epitope specific for HCV core 129-137 (t*24/c129) or HCV NS3 1296-1304
      (t*24/ns1294), directly ex vivo. RESULTS: The mDC and pDC populations changed in
      parallel (P < 0.05), showing a significant transient decrease at weeks 12 and 16
      during the therapy, and then recovering. However, neither of the tetramer results
      showed a direct correlation with the kinetics of peripheral DCs. CONCLUSIONS:
      There is an apparent effect of antiviral therapy or a subsequent reduction of HCV
      on host immunity, but the effect may not include the induction of CTLs in CHC.

PMID- 16988765
TI  - An audit of the outcome of long-term biliary stenting in the treatment of common
      bile duct stones in a general hospital.
AB  - BACKGROUND: This study audited the clinical outcome of a cohort of patients with
      choledocholithiasis treated with long-term biliary stenting in order to determine
      the feasibility of this practice. METHODS: Over 2 years, 83 patients with
      symptomatic choledocholithiasis were treated with long-term stenting because they
      either refused further treatments or were medically unfit for further procedures
      after the initial endoscopic retrograde cholangiopancreatography (ERCP).
      Recurrence of clinical events, need for stent change, morbidity, and mortality
      were analyzed. As a secondary analysis, published data on long-term biliary
      stenting were reviewed. RESULTS: ERCP and biliary stenting were successful in all
      cases with no complications. The mean follow-up was 19 months (1-103 months). The
      median number of ERCPs performed was 1 (1-4). The mean duration of stent patency
      was 12.4 months (1-54.8 months). A total of 28 clinical events (cholangitis, 71%)
      occurred in 24 patients during follow-up, for a late complication rate of 33.7%.
      ERCP was repeated and the stents changed on 15 occasions in 11 asymptomatic
      patients with abnormal liver function tests detected on routine follow-up. No
      biliary-related mortality occurred. Review of published data revealed a mean late
      complication rate of 22.4% (0%-64%), a biliary-related mortality rate of 3.5% (0%
      21.1%), and a nonbiliary-related mortality rate of 20.8% (0%-60.3%). CONCLUSIONS:
      Long-term biliary stenting is a feasible option for patients who decline or are
      medically unfit for further elective endoscopic or surgical procedures. Close
      follow-up is mandatory to detect and treat late complications.

PMID- 16988766
TI  - Eupatilin attenuates bile acid-induced hepatocyte apoptosis.
AB  - BACKGROUND: In cases of cholestasis, bile acids induce hepatocyte apoptosis by
      activating death receptor-mediated apoptotic signaling cascades. Eupatilin (5,7
      dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredient found
      in Artemisia asiatica and exhibits cytoprotective effects against experimentally
      induced gastrointestinal, pancreatic, and hepatic damage. This study was
      undertaken to examine if eupatilin modulates bile acid-induced hepatocyte
      apoptosis. METHODS: Huh-BAT cells, a human hepatocellular carcinoma cell line
      stably transfected with a bile acid transporter, were used in this study.
      Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride
      staining, and its signaling cascades were explored by immunoblot analysis. Kinase
      signaling was evaluated by immunoblotting and by using selective inhibitors.
      Eupatilin's in vivo effect on bile acid-induced hepatocyte apoptosis was explored
      in bile duct-ligated rats. RESULTS: Eupatilin significantly reduced bile acid
      mediated hepatocyte apoptosis by attenuating bile acid-induced caspase 8
      cleavage. Eupatilin diminished the bile acid-induced activation of mitogen
      activated protein kinases, including p38 mitogen-activated protein kinase and c
      Jun N-terminal kinase. In particular, the eupatilin-mediated inhibition of bile
      acid-induced c-Jun N-terminal kinase activation was found to be responsible for
      attenuating caspase 8 cleavage. Moreover, eupatilin diminished hepatocyte
      apoptosis in bile duct-ligated rats. CONCLUSIONS: Eupatilin attenuates bile acid
      induced hepatocyte apoptosis by suppressing bile acid-induced kinase activation.
      Therefore, eupatilin might be therapeutically efficacious in a variety of human
      liver diseases associated with cholestasis.

PMID- 16988767
TI  - Immunosuppression in patients with severe acute pancreatitis.
AB  - BACKGROUND: In severe acute pancreatitis (SAP), immunologic impairment in the
      early phase may be linked to subsequent infectious complications. In this study,
      immunologic alterations in patients with SAP were analyzed, and immunologic
      parameters related to infectious complications were clarified. METHODS: A total
      of 101 patients with SAP were analyzed retrospectively. Various immunologic
      parameters on admission were analyzed and compared between the infection group
      and noninfection group during SAP. Furthermore, chronologic change in the
      lymphocyte count was investigated, and its utility for predicting infection was
      compared with conventional scoring systems. RESULTS: Serum immunoglobulin G
      (IgG), serum IgM, lymphokine-activated killer cell activity, and natural killer
      cell activity were low, and the incidence of abnormally low values was 50.0%,
      65.0%, 45.5%, and 42.4%, respectively. Serum complement factor 3 was
      significantly negatively correlated with the APACHE II score. The lymphocyte
      count was decreased below the normal range, and was significantly negatively
      correlated with the APACHE II score. CD4-, CD8-, and CD20-positive lymphocyte
      counts were below the normal range, and CD4- and CD8-positive lymphocyte counts
      were significantly lower in the infection group. The lymphocyte count on day 14
      after admission was significantly lower in the infection group and was more
      useful for predicting infection than conventional scoring systems. CONCLUSIONS:
      Immunosuppression occurs from the early phase in SAP, and quantitative impairment
      of lymphocytes, mainly T lymphocytes, may be closely related to infectious
      complications during SAP. CD4- and CD8-positive lymphocyte counts on admission
      and the lymphocyte count on day 14 after admission may be useful for predicting
      infection.

PMID- 16988768
TI  - Hepatitis B virus RNA is measurable in serum and can be a new marker for
      monitoring lamivudine therapy.
AB  - BACKGROUND: Changes in the serum hepatitis B virus (HBV) RNA level during
      lamivudine therapy were compared to those in the serum HBV DNA and HBV core
      related antigen (HBVcrAg) levels in 24 patients with chronic hepatitis B.
      METHODS: For measurement of HBV RNA, total nucleic acid was extracted from serum
      samples and treated with RNase-free DNase I. After cDNA synthesis from extracted
      RNA, HBV RNA was measured by real-time detection polymerase chain reaction.
      RESULTS: The peak fraction of HBV RNA in serum samples was consistent with peak
      fractions of HBV DNA and HBV core protein in a sucrose gradient analysis,
      indicating that HBV RNA was incorporated into virus particles. All levels of HBV
      DNA, HBV RNA, and HBVcrAg decreased gradually during lamivudine therapy (P <
      0.001 for all). The amount of decrease from the start of lamivudine therapy was
      significantly higher for HBV DNA than for HBV RNA or HBVcrAg during 6 months of
      lamivudine therapy (P < 0.001 for all). However, a similar difference was not
      seen between HBV RNA and HBVcrAg levels during that period. The HBV RNA level was
      significantly correlated (P < 0.001 for all) with levels of HBV DNA and HBVcrAg
      both at the beginning and 2 months after the start of lamivudine therapy.
      CONCLUSIONS: HBV RNA is detectable in serum in a form indicating incorporation
      into virus particles, and its serum level might serve as a new viral marker with
      a significance different from that of HBV DNA in lamivudine therapy.

PMID- 16988769
TI  - Preproenkephalin hypermethylation in the pure pancreatic juice compared with p53
      mutation in the diagnosis of pancreatic carcinoma.
AB  - BACKGROUND: Aberrant methylation of CpG islands is a common mechanism for the
      dysregulation of tumor suppressor genes in a variety of human malignancies.
      Preproenkephalin ppENK) hypermethylation is recognized in 90% of pancreatic
      carcinoma (PCa) tissues, but not in normal pancreas. We analyzed ppENK
      hypermethylation in pure pancreatic juice (PPJ) in patients with PCa, intraductal
      papillary mucinous neoplasms (IPMN), and chronic pancreatitis (CP), and
      elucidated its usefulness as a marker in the diagnosis of PCa compared with p53
      mutation. METHODS: PPJ was collected endoscopically from 28 patients with PCa, 15
      patients with IPMN, and 20 patients with CP. DNA was extracted from the
      supernatant and the sediment of PPJ. Methylation-specific polymerase chain
      reaction was performed for hypermethylation analysis of ppENK. In addition,
      single-strand conformation polymorphism and direct sequencing were performed
      simultaneously to identify p53 mutations. RESULTS: The incidence of ppENK
      hypermethylation in the supernatant and/or the sediment of PPJ was 50% (14 of 28)
      in patients with PCa. In contrast, the incidence of ppENK hypermethylation was
      26.7% (4 of 15) in patients with IPMN, and 5% (1 of 20) in patients with CP (P <
      0.002). The incidence of p53 mutations in the PPJ was 42.9% (12 of 28) in
      patients with PCa and 0% (0 of 20) in patients with CP. Furthermore, the
      incidence of ppENK hypermethylation and/or p53 mutations in the PPJ was enhanced
      to 67.9% (19 of 28) in patients with PCa in the combination assay. CONCLUSIONS:
      These results suggest that ppENK hypermethylation in PPJ is specific for cancer,
      and the combination assay with p53 enhances the genetic diagnosis of PCa.

PMID- 16988770
TI  - Relapsing acute pancreatitis due to ampullary adenoma in a patient with familial
      adenomatous polyposis.
AB  - A patient with familial adenomatous polyposis (FAP) presented with a relapsing
      attack of acute pancreatitis. Evaluation using computed tomography,
      ultrasonography, and duodenoscopy revealed an ampullary adenoma, which was
      classified as Spigelman's stage III according to Spigelman's criteria. The
      patient underwent a pylorus-resected pancreatoduodenectomy, and has had no
      abdominal pain suggesting acute pancreatitis for 1 year after surgery. Only a few
      reports of acute pancreatitis due to ampullary neoplasms in patients with FAP are
      available. Relapsing acute pancreatitis is another surgical indication for
      premalignant periampullary neoplasms in FAP.

PMID- 16988771
TI  - Dynamic pelvic three-dimensional computed tomography for investigation of pelvic
      abnormalities in patients with rectocele and rectal prolapse.
AB  - BACKGROUND: Dynamic three-dimensional computed tomography (D-3DCT: high-speed
      helical scanning during defecation) was used for morphological evaluation of
      intrapelvic structures in patients with rectal prolapse and rectocele. METHODS:
      Twenty-five patients with rectal prolapse or rectocele diagnosed by conventional
      defecography (CD) or clinical findings were additionally investigated with D
      3DCT. D-3DCT images were acquired using a multislice CT system with a 16-row
      detector during simulated defecation. Helical scanning was performed with a slice
      thickness of 1 mm, a helical pitch of 15 s/rotation, and a table movement speed
      of 35 mm/s. The contrast medium, 100 ml of iopamidol (370 mg/ml), was injected at
      a rate of 2.5 ml/s to enhance contrast with other structures, and scan start was
      triggered by using a function for automatically determining the optimal scan
      timing. RESULTS: Among the eight patients with rectocele, additional intrapelvic
      disorders were diagnosed in five (enterocele, 4; cystocele, 1; and uterine
      prolapse, 1) with D-3DCT. In the 17 patients with rectal prolapse, concomitant
      intrapelvic disorders were found in six (intussusception, 3; cystocele, 2;
      uterine prolapse, 2; rectocele, 1; and vaginal prolapse, 1). CONCLUSIONS: D-3DCT
      can be a useful diagnostic tool for investigation of pelvic pathology in patients
      with rectocele and rectal prolapse.

PMID- 16988772
TI  - Immune complex of hepatitis C virus particles detected by immunogold electron
      microscopy.

PMID- 16988773
TI  - Pulmonary tumor embolism in a case of hepatocellular carcinoma.

PMID- 16988774
TI  - Role of corticotropin-releasing factor in stress-related visceral hyperalgesia.

PMID- 16988775
TI  - Understanding the precise function of interferon regulatory factor 3 in hepatitis
      C virus replication will lead to a new strategy for therapy.

PMID- 16988776
TI  - Do DCs influence the antiviral effect of interferon/ribavirin by changing their
      profile during the therapy?

PMID- 16988777
TI  - Eupatilin has an antiapoptotic action on hepatocytes, in contrast to apoptotic
      actions on other cells.

PMID- 16988778
TI  - Abdominovaginal sacral colpoperineopexy: patient perceptions, anatomical
      outcomes, and graft erosions.
AB  - This is a retrospective analysis of 169 consecutive patients who underwent the
      abdominovaginal sacral colpoperineopexy. POP-Q measurements, patient willingness
      to have the same surgery again, and mesh erosions were recorded during follow-up
      visits. Patients whose erosion responded to office excision were defined as
      having minor mesh erosion. Patients with persistent erosions requiring outpatient
      surgical excisions were defined as having major mesh erosion. For the 122
      patients with 12-month follow-up, all POP-Q points improved (p<0.005) compared
      with preoperative measurements. The response to the question "Would you go
      through the same surgery again?" was "yes" 77.3% of the time and "no" 4.9% of the
      time. Minor mesh erosion rate was 5.9% (10/169). Major erosion rate was 0.6%
      (1/169). In conclusion, when combined with paravaginal defect repair and Burch
      urethropexy, the abdominovaginal sacral colpoperineopexy effectively addresses
      all support defects in patients with advanced prolapse. The procedure is
      associated with a high level of patient willingness to have the same surgery
      again, and it is achieved with low erosion rate.

PMID- 16988779
TI  - Dyspareunia and chronic pelvic pain after polypropylene mesh augmentation for
      transvaginal repair of anterior vaginal wall prolapse.
AB  - Synthetic mesh augmentations for pelvic floor reconstructive surgeries are
      increasing in usage and popularity. Many studies are focusing on the anatomical
      success rates of transvaginal anterior compartment repairs with synthetic mesh,
      with minimal attention on its postoperative complications. We present a case
      report on a 59-year-old postmenopausal woman who underwent an anterior repair
      with 6x4-cm polypropylene mesh. Postoperatively, she developed severe dyspareunia
      and debilitating chronic pelvic pain. The patient failed conservative medical
      therapy and now requests complete removal of the synthetic mesh.

PMID- 16988780
TI  - Electrotransformation of Thermoanaerobacter ethanolicus JW200.
AB  - Electrotransformation of Thermoanaerobacter ethanolicus JW200 was achieved using
      the plasmid, pTE16, and a pUC-based suicide vector, pTEA2. The construct pTE16 is
      based on the Escherichia coli-Clostridium perfringens shuttle vector pJIR715 and
      contains a thermostable chloramphenicol (Cm) resistance cassette. Evidence
      supporting transformation was provided by extracting plasmid pTE16 from
      presumptive transformants of T. ethanolicus and by PCR specific to the
      chloramphenicol acetyltransferase (cat) gene on the vector pTEA2. Transformation
      frequencies of plasmid pTE16 and pTEA2 were 50 +/- 7.4 and 30 +/- 4.2
      transformants per mug plasmid DNA. The results provide the first unequivocal gene
      transfer method functional in T. ethanolicus.

PMID- 16988781
TI  - Cloning and expression of Penicillium minioluteum dextranase in Saccharomyces
      cerevisiae and its exploitation as a reporter in the detection of mycotoxins.
AB  - A dextranase gene from Penicillium minioluteum (strain IMI068219) has been
      cloned, sequenced and expressed in Saccharomyces cerevisiae via fusion of the DNA
      segment encoding the mature dextranase protein with alpha-factor signal sequence,
      and insertion into the GAL1-controlled expression vector pYES2/CT. Galactose
      induced expression yielded extracellular dextranase activity of 0.63 units/ml and
      cell-associated dextranase activity of 0.48 units/ml, after 24 h incubation. The
      dextranase construct was introduced into a strain of S. cerevisiae expressing the
      human cytochrome P450 3A4 (CYP3A4) and the cognate reductase, which was then used
      to develop a microplate toxicity bioassay. Toxicity was signalled as inhibition
      of dextranase activity, assayed fluorimetrically. This novel bioassay was
      assessed using six economically significant mycotoxins.

PMID- 16988782
TI  - Characterization and application of aptamers for Taq DNA polymerase selected
      using an evolution-mimicking algorithm.
AB  - Using an evolution-mimicking algorithm (EMA), we have recently identified DNA
      aptamers that inhibit Taq DNA polymerase. In the present study, we have attempted
      to improve further the inhibitory activities of aptamers, as well as to
      characterize those aptamers with the most potent inhibitory activities. To
      characterize the most potent aptamer and demonstrate its applicability, the
      abilities to inhibit Tth DNA polymerase and to modulate specific amplification in
      PCR were investigated. This aptamer inhibited both Tth DNA polymerase and Taq DNA
      polymerase and improved the specificity of detection of a low-copy-number target
      gene in PCR using these DNA polymerases.

PMID- 16988783
TI  - Modeling suppression of cell death by Bcl-2 over-expression in myeloma NS0 6A1
      cells.
AB  - A novel population-balance model was employed to evaluate the suppression of cell
      death in myeloma NS0 6A1 cells metabolically engineered to over-express the
      apoptotic suppressor Bcl-2. The model is robust in its ability to simulate cell
      population dynamics in batch suspension culture and in response to thymidine
      induced growth inhibition: 89% of simulated cell concentrations are within two
      standard deviations of experimental data. Kinetic rate constants in model
      equations suggest that Bcl-2 over-expression extends culture longevity from 6
      days to at least 15 days by suppressing the specific rate of early apoptotic cell
      formation by more than 6-fold and necrotic cell formation by at least 3-fold,
      despite nearly a 3-fold decrease in initial cell growth rate and no significant
      change in the specific rate of late apoptotic cell formation. This computational
      analysis supports a mechanism in which Bcl-2 is a common mediator of early
      apoptotic and necrotic events occurring at rates that are dependent on cellular
      factors accumulating over time. The model has current application to the rational
      design of cell cultures through metabolic engineering for the industrial
      production of biopharmaceuticals.

PMID- 16988784
TI  - Recombinant production of docosahexaenoic acid in a polyketide biosynthesis mode
      in Escherichia coli.
AB  - The docosahexaenoic acid (DHA) biosynthesis gene cluster (pDHA3) from the DHA
      producing Moritella marina strain MP-1 includes the genes pfaA, pfaB, pfaC, and
      pfaD, which are similar to the genes of polyketide biosynthesis. When this
      cluster was co-expressed in Escherichia coli with M. marina MP-1 pfaE, which
      encodes phosphopantetheinyl transferase, DHA was biosynthesized. The maximum
      production of DHA (5% of total fatty acids) was observed at 15 degrees C. This is
      the first report of the recombinant production of DHA in a polyketide
      biosynthesis mode.

PMID- 16988785
TI  - Assembling a novel bifunctional cellulase-xylanase from Thermotoga maritima by
      end-to-end fusion.
AB  - An artificial, bifunctional, thermostable cellulase-xylanase enzyme from
      Thermotoga maritima by gene fusion. The fusion protein exhibited both cellulase
      and xylanase activity when xynA was fused downstream of cel5C but no activities
      were shown when xynA was fused upstream of cel5C. The enzyme was optimally active
      at pH 5.0 and 80 degrees C over 30 min. E. coli expressed the fusion enzyme, with
      an apparent molecular mass of approximately 152 kDa by carboxymethyl cellulose-
      and xylan-SDS-PAGE.

PMID- 16988786
TI  - Alginate/carbon composite beads for laccase and glucose oxidase encapsulation:
      application in biofuel cell technology.
AB  - Alginate-carbon beads were prepared in order to develop a biocompatible matrix
      for laccase and glucose oxidase immobilization for application in biofuel cell
      technology. The enzyme loading capacity was high (91%) in pure alginate beads for
      glucose oxidase. For laccase, the loading capacity was enhanced from 75% to 83%
      by introducing carbon. Desorption out of the matrix was controlled by the
      enzymes' diffusion and reached a plateau after 40 h for laccase and 70 h for
      glucose oxidase. Two-thirds of both enzymes was irreversibly retained inside the
      alginate beads. This proportion increased to 80% for laccase in combined
      alginate/carbon beads. Half-life of the adsorbed enzyme was enhanced to 74 days
      for laccase in carbon/alginate beads and 45 days for glucose oxidase in pure
      alginate as compared to 38 days and 23 days for free enzymes, respectively.

PMID- 16988787
TI  - Interferon-alpha and transforming growth factor-beta co-induce growth inhibition
      of human tumor cells.
AB  - A hallmark of resistance to type I interferons (IFNs) is the lack of
      antiproliferative responses. We show here that costimulation with IFN-alpha and
      transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative
      activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. A
      DNA microarray-based search for proliferation control genes involved that are
      cooperatively activated by IFN-alpha and TGF-beta, yielded 28 genes. Among these
      are the insulin-like growth factor-binding protein 3 (IGFBP3) and the calcium
      binding protein S100A2; we demonstrate, that recombinant IGFBP3 protein is a
      potent growth inhibitor requiring TGF-beta activity. The antiproliferative
      activity of S100A2 is significantly enhanced by IFN-alpha in stably transfected
      ME15 or D10 cell lines. We show for the first time that IFN-alpha is a potent
      inducer of intracellular calcium release required for activation of S100A2. Our
      study provides a functional link between IFN-alpha and TGF-beta signaling and
      extends the function of IFN signaling to calcium-sensitive processes.

PMID- 16988788
TI  - New developments in the biological functions of lysophospholipids.
AB  - Lysophospholipids have long been recognized as membrane phospholipid metabolites,
      but only recently has their role as intercellular signaling molecules been
      appreciated. Two of the best-studied lysophospholipids, LPA and S1P, signal
      through cognate G-protein-coupled receptors to activate many well-known
      intracellular signaling pathways, leading to a variety of biologically important
      cell responses. Lysophospholipids and their receptors have been found in a wide
      range of tissues and cell types, indicating their importance in many
      physiological processes, including reproduction, vascular development, cancer and
      nervous system function. This article will focus on the most recent findings
      regarding the biological functions of lysophospholipids in mammalian systems,
      specifically as they relate to health and disease.

PMID- 16988789
TI  - Psychiatric disorders among foreign-born and US-born Asian-Americans in a US
      national survey.
AB  - BACKGROUND: Among Hispanics, Non-Hispanic Whites and Non-Hispanic Blacks studies
      have found lower risk for psychiatric disorders among the foreign-born than among
      the US-born. We examine the association of nativity and risk for psychiatric
      disorder in a national sample of the Asian-American (AA) population. METHODS:
      Data on 1,236 AAs from the National Epidemiological Survey of Alcohol and Related
      Conditions (NESARC) are analyzed using logistic regression and discrete time
      survival models to specify differences between the foreign-born and US-born in
      the lifetime occurrence of mood, anxiety and substance use disorders. RESULTS:
      Foreign-born AAs had significantly lower risk for all classes of disorder
      compared with US-born AAs (OR = 0.16-0.59). Risk for all classes of disorder was
      lowest for those foreign-born AAs who arrived in the US as adults. Among foreign
      born AAs risk of first onset was lowest relative to the US-born in years prior to
      their arrival in the US and tended to rise to levels equal to that of the US-born
      with longer duration of residence in the US. CONCLUSIONS: Among AAs, risk for
      psychiatric disorders is lower among the foreign-born than among the US-born. The
      pattern of change in risk over time suggests that both the developmental timing
      and the duration of experience in the US contribute to increases in risk.

PMID- 16988791
TI  - Evidence of white matter involvement in SCA 7.

PMID- 16988792
TI  - Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces
      spasticity-related pain : a double-blind placebo-controlled cross-over trial.
AB  - About 30% of patients with chronic upper motor neuron syndrome (UMNS) suffer from
      disabling spasticity-related pain not sufficiently correctable by conventional
      treatment. Delta9-tetrahydrocannabinol (Delta(9)-THC) was reported to add benefit
      in the treatment of pain in patients with multiple sclerosis (MS). The question
      arose whether synthetic cannabinoids with lower potential for psychotropic side
      effects could be effective as well. To evaluate the safety and efficacy of low
      dose treatment with the synthetic cannabinoid Nabilone (1 mg per day) on
      spasticity-related pain a placebo-controlled double-blind crossover trial was
      performed.11 out of 13 included patients completed the study. The 11-Point-Box
      Test showed a significant decrease of pain under Nabilone (p < 0.05), while
      spasticity, motor function and activities of daily living did not change. 5
      patients reported side effects: one moderate transient weakness of the lower
      limbs (Nabilone phase, drop out), three mild drowsiness (two Nabilone, one
      placebo) and one mild dysphagia (placebo). One patient was excluded from the
      study due to an acute relapse of multiple sclerosis (Nabilone phase, drop out).
      Nabilone 1 mg per day proved to be a safe and easily applicable option in the
      care of patients with chronic UMNS and spasticity-related pain otherwise not
      controllable.

PMID- 16988793
TI  - Neuronavigation and surgery of intracerebral tumours.
AB  - Approximately four decades after the successful clinical introduction of
      framebased stereotactic neurosurgery by Spiegel and Wycis, frameless stereotaxy
      emerged to enable more elaborate image guidance in open neurosurgical procedures.
      Frameless stereotaxy, or neuronavigation, relies on one of several different
      localizing techniques to determine the position of an operative instrument
      relative to the surgical field, without the need for a coordinate frame rigidly
      fixed to the patients' skull. Currently, most systems are based on the optical
      triangulation of infrared light sources fixed to the surgical instrument. In its
      essence, a navigation system is a three-dimensional digitiser that correlates its
      measurements to a reference data set, i.e. a preoperatively acquired CT or MRI
      image stack. This correlation is achieved through a patient-to-image registration
      procedure resulting in a mathematical transformation matrix mapping each position
      in 'world space' onto 'image space'. Thus, throughout the remainder of the
      surgical procedure, the position of the surgical instrument can be demonstrated
      on a computer screen, relative to the CT or MRI images. Though neuronavigation
      has become a routinely used addition to the neurosurgical armamentarium, its
      impact on surgical results has not yet been examined sufficiently. Therefore, the
      surgeon is left to decide on a case-by-case basis whether to perform surgery with
      or without neuronavigation. Future challenges lie in improvement of the interface
      between the surgeon and the neuronavigator and in reducing the brainshift error,
      i.e. inaccuracy introduced by changes in tissue positions after image
      acquisition.

PMID- 16988794
TI  - Receptor-receptor interactions in central cardiovascular regulation. Focus on
      neuropeptide/alpha(2)-adrenoreceptor interactions in the nucleus tractus
      solitarius.
AB  - The nucleus tractus solitarii (NTS) is a key nucleus in central cardiovascular
      control. In this mechanism it is well known the role of the alpha(2)
      adrenoreceptors for the modulation of the autonomic pathways. Moreover a number
      of neuropeptides described in the NTS, including Neuropeptide Y (NPY), Galanin
      (GAL) and Angiotensin II (Ang II), have different roles in regulating the
      cardiovascular function within this nucleus. We show in this review several data
      which help to understand how these neuropeptides (NPY, GAL and Ang II) could
      modulate the cardiovascular responses mediated through alpha(2)-adrenoreceptors
      in the NTS. Also we show for the first time the interactions between
      neuropeptides in the brain, specifically the interactions between NPY, GAL, and
      Ang II, and its functional relevance for central cardiovascular regulation. These
      data strength the role of neuropeptides on central autonomic control and provide
      some evidences to understand the neurochemical mechanisms involved in the
      cardiovascular responses from the NTS.

PMID- 16988795
TI  - Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of
      serotonergic platelet measures between suicidal individuals, nonsuicidal patients
      with major depression and healthy subjects.
AB  - BACKGROUND: A robust association between "suicidality" and deficits of the
      serotoninergic neurotransmission has been claimed in the past. However, many
      studies having investigated the relationship between suicidality and peripheral
      indicators of serotoninergic neurotransmission suffer from considering only one
      or a very small number of potentially useful serotoninergic parameters, whereas a
      synoptic multidimensional approach appears to be more appropriate. Furthermore,
      the psychiatric context within which suicidal behaviour occurs should be
      considered when interpreting biochemical findings of patients with suicidal
      ideation and suicide attempts. METHODS: In the present study 5 peripheral
      serotonergic markers, (platelet 5HT concentration, 5HT uptake activity, 5HT(2A)
      receptor binding characteristics, MAO-B activity and tryptophan concentration in
      plasma) were assessed simultaneously. Of the 60 acutely suicidal inpatients (ICD
      10: F43.xx, n = 52; F31/32/33, n = 8), 45 were suicide attempters. Data of 28
      nonsuicidal patients with major depression (F31, n = 4; F32, n = 14; F33, n = 10)
      and 123 healthy volunteers represented the control groups. RESULTS: Mean platelet
      5HT concentration was significantly lower in suicidal inpatients when compared to
      nonsuicidal depressed patients, but did not differ from the figure in healthy
      subjects. Nonsuicidal depressed patients showed significantly higher mean
      platelet-5HT concentration than healthy controls. Mean V(max) of 5HT uptake in
      washed platelets, but not in platelet-rich plasma, was significantly higher in
      suicidal patients than in healthy controls, not, however, when compared to
      nonsuicidal depressed patients. Mean K(D) for the platelet 5HT(2A) receptor and
      MAO-B activity were significantly lower in suicidal patients as compared to
      nonsuicidal depressed patients and healthy controls. The observed differences in
      peripheral serotonergic markers between groups are partially due to a significant
      gender effect. A lower MAO-B activity was observed only in suicidal females,
      while the higher V(max) of 5HT uptake in washed platelets of suicidal patients
      was due to suicidal males. CONCLUSIONS: In view of conflicting observations made
      by other authors and the present findings on suicidal patients with adjustment
      disorder it remains doubtful whether and if so to which extent platelet studies
      can provide valid information on serotonergic mechanisms related to suicidal
      behaviour.

PMID- 16988797
TI  - Homocysteine but not neopterin declines in demented patients on B vitamins.
AB  - Inflammation and immune system activation seem to play an important role in the
      development and progression of dementia. Hyperhomocysteinemia is common in
      various forms of dementia, and a significant relationship was found between
      concentrations of homocysteine and immune activation marker neopterin. B vitamin
      supplementation is able to slow-down homocysteine formation in patients. In an
      open-label study, effects of B vitamin supplementation (Beneuran compositum ) on
      concentrations of homocysteine and neopterin were investigated in 58 patients
      with Alzheimer's disease (n=30), vascular dementia (n=12) and mild cognitive
      impairment (n=16). In all groups of patients, a significant percentage of
      patients presented with homocysteine concentrations >15 micromol/L and with
      elevated concentrations of immune activation marker neopterin. Decline of
      homocysteine concentrations was observed after one month of B vitamin
      supplementation (all p<0.01; paired Kruskal-Wallisn-test). By contrast, neopterin
      concentrations remained unchanged (all p>0.05). B vitamin supplementation in
      patients with various forms of dementia did not influence neopterin
      concentrations, which indicates that the degree of immune activation and
      inflammation remained unchanged. The question remains, if lowering of
      homocysteine by folate supplementation alone could have any beneficial effect to
      modulate the course of dementia development and if longer period of
      supplementation would also ameliorate immune system activation status.

PMID- 16988796
TI  - Changes in the neuronal activity in the pedunculopontine nucleus in chronic MPTP
      treated primates: an in situ hybridization study of cytochrome oxidase subunit I,
      choline acetyl transferase and substance P mRNA expression.
AB  - The pedunculopontine nucleus is a mesencephalic nucleus that has widespread and
      reciprocal connections with the basal ganglia. It has been implicated in the
      physiopathology of akinesia, rigidity, gait failure and sleep disorders
      associated with Parkinson's disease. In this study, in situ hybridization was
      used to examine the changes in neuronal metabolic activity (measuring cytochrome
      oxidase subunit I) and in the level of acetylcholine and Substance P synthesis in
      the pedunculopontine nucleus of monkeys chronically treated with MPTP.
      Significant reductions were observed in cytochrome oxidase subunit I (p = 0.001),
      choline acetyl transferase (p = 0.003) and substance P (p = 0.006) mRNA
      expression in parkinsonian animals compared with controls, indicating that
      pedunculopontine cholinergic neurons activity decreases with parkinsonism.

PMID- 16988798
TI  - Endophenotype approach to developmental psychopathology: implications for autism
      research.
AB  - This paper discusses the utility of the endophenotype approach in the study of
      developmental psychopathology. It is argued that endophenotype research holds
      considerable promise for the study of gene-brain/cognition-behaviour pathways for
      developmental disorders. This paper outlines the criteria for determining useful
      endophenotypes. Possible endophenotypes for autism are discussed as an example of
      an area where endophenotype research on developmental disorders may be fruitful.
      It is concluded that although the endophenotype approach holds promise for the
      study of gene-brain/cognition-behaviour pathways, much work remains to be done in
      order to validate endophenotype measures. It is also noted that the changing
      nature of any developmental psychopathology poses a particular challenge to this
      type of research.

PMID- 16988799
TI  - Cavitary acetabular defects treated with morselized cancellous bone graft and
      cementless cups.
AB  - The use of impacted morselized cancellous bone grafts in conjunction with
      cementless hemispherical acetabular cups for treatment of AAOS type II acetabular
      cavitary deficiencies was evaluated in a retrospective study of 23 primary and 24
      revision total hip arthroplasties, at a mean follow-up of 7.9 and 8.1 years,
      respectively. All primary hips received autografts, while all revision hips
      received allografts. Modified Harris Hip Scores for primary and revision hip
      replacements increased from a pre-operative mean of 37 and 47 to a postoperative
      mean of 90 and 86, respectively. All 23 autografts and 23 out of 24 cancellous
      allografts were radiographically incorporated without evidence of resorption.
      There were no instances of infection, component migration, or cases requiring
      subsequent acetabular revision. We conclude that impacted morselized cancellous
      bone-graft augmentation of cementless cups is a viable surgical option for AAOS
      type II cavitary acetabular defects.

PMID- 16988800
TI  - Extra-osseous fat fluid level: a specific sign for osteomyelitis.
AB  - Osteomyelitis may pose as a diagnostic dilemma on various imaging modalities and
      may be confused with neoplasms and other pathology. Although a rare finding,
      extra-osseous fat fluid level, especially when associated with spongy bone
      destruction, can be considered a specific sign of osteomyelitis. Previously, only
      two cases of extra-osseous fat fluid level in osteomyelitis have been reported,
      one on computed tomography (CT) and the other on magnetic resonance imaging
      (MRI). The former was a case of septic arthritis with intra-articular fat fluid
      level. A case of osteomyelitis is presented with the demonstration of extra
      osseous fat fluid level. Our case is unique in providing exquisite CT and MRI
      correlation.

PMID- 16988801
TI  - Pellegrini-Stieda disease: a heterogeneous disorder not synonymous with
      ossification/calcification of the tibial collateral ligament-anatomic and imaging
      investigation.
AB  - OBJECTIVE: Ossification/calcification around the medial femoral condyle has been
      known as Pellegrini-Stieda (PS) disease for almost 100 years. Little attention
      has been given to magnetic resonance (MR) imaging characteristics. Our purpose is
      to demonstrate the anatomy in the medial femoral compartment and imaging findings
      of PS disease, determining the sites and patterns of ossification. DESIGN AND
      PATIENTS: In a cadaveric study seven specimens were dissected to show the
      anatomic relations of the tibial collateral ligament (TCL) and the tendon of the
      ischiocondylar part of the adductor magnus muscle, in the medial femoral
      epicondyle. In order to determine the nature of ossification/calcification in PS
      disease, MR imaging and radiographic findings in nine patients were analyzed by
      two observers with attention to the specific site, shape, and orientation of the
      ossification and its relationship to the tibial collateral ligament (TCL) and
      adductor magnus tendon. Available clinical history was recorded. A classification
      system addressing different sites and patterns of ossification was developed.
      RESULTS: The anatomic study showed that the TCL and the adductor magnus tendon
      insert at different sites in the medial femoral condyle and there is no
      continuation; however, some fibers of the posterior bundle of the TCL overlap the
      anterior aspect of the adductor magnus tendon. The imaging study showed that
      shape, orientation, and location of the abnormal calcification and ossification
      were similar on radiographic and MR imaging analysis. Ossification had an
      inferior orientation in six cases, a superior orientation in two cases, and both
      in one case. Four patterns of ossification were noted: (I) a beak-like appearance
      with an inferior orientation and femoral attachment was present in five cases;
      (II) a drop-like appearance with an inferior orientation, parallel to the femur,
      was evident in one case; (III) an elongated appearance with a superior
      orientation, parallel to the femur, was seen in two cases; and (IV) a beak-like
      appearance with an inferior and superior orientation, attached to the femur, was
      seen in one case. The ossification was present in the TCL in six cases, in the
      adductor magnus tendon in two cases, and in both in one case. The coronal plane
      was best in detecting and categorizing the ossification. CONCLUSION: Our data
      indicate that ossification in PS disease is not confined to the TCL but may also
      involve the adductor magnus tendon. In some cases, it can be related to the
      anatomic proximity (overlap) of the fibers of these two structures. PS disease
      should not be regarded as synonymous with ossification of the TCL. The
      ossification may be classified into four types. No clinical differences among
      these types appear to exist.

PMID- 16988802
TI  - [Drug-related disorders of water and electrolyte metabolism].
AB  - Pharmacologic treatment may lead to diverse disturbances of water and electrolyte
      metabolism as adverse drug events. Diuretics are particularly likely to cause
      these complications typically including volume depletion, metabolic alkalosis,
      hyponatremia, and hypokalemia. Salt and water retention with edema formation is
      most frequently elicited by antihypertensives, steroid hormones, and nonsteroidal
      anti-inflammatory drugs. Drug-induced disorders of Na+ concentration may usually
      be attributed to altered antidiuretic hormone (ADH) effects, either as diabetes
      insipidus or as the syndrome of inappropriate ADH secretion. With hyper- and
      hypokalemia, redistribution between intra- and extracellular fluid as well as
      renal excretion play a role. Strategies to prevent these adverse drug reactions
      include careful consideration of risk factors and clinical and laboratory
      controls in the course of treatment.

PMID- 16988803
TI  - [Prevention of sudden cardiac death].
AB  - The problem of sudden cardiac death (SCD) is complex and many questions
      concerning the pathophysiologic mechanism are still unanswered. At present the
      only reliable way of recognizing high risk patients is by means of left
      ventricular dysfunction, measured as LV-EF<or=35%. The positive predictive
      accuracy for other non-invasive risk markers is too low. So far, antiarrhythmic
      drugs have failed to successfully prevent SCD. More than 25 years of clinical
      experience with the implantable defibrillator (ICD) with its continuous technical
      improvement has made the ICD the most effective weapon against SCD. Its
      effectiveness has been demonstrated in many prospective trials and the use of the
      ICD is fully enclosed within the current guidelines for the prevention of SCD.
      Guidelines do not, however, replace the physician's judgement and experience to
      correctly evaluate the patient's status. ICD therapy in the primary and secondary
      prevention of heart failure, which is often accompanied by a high risk of SCD is,
      however, not justified without guideline-adjusted therapy.

PMID- 16988804
TI  - [Cardioprotection by means of Candesartan in cardiac insufficiency. CHARM overall
      partial evaluation (Candesartan in heart failure assessment of reduction in
      mortality and morbidity)].

PMID- 16988805
TI  - [Modern pharmacotherapy of supraventricular and ventricular cardiac arrhythmia.
      An update for conventional therapy].
AB  - Currently the pharmacological approach still represents the mainstay in the acute
      phase of arrhythmia management as well as in the chronic treatment phase of
      specific entities such as atrial fibrillation. However, non-pharmacological
      options have recently emerged as frequently used first-line tools for the
      treatment of various supraventricular and ventricular heart rhythm disturbances.
      Nevertheless, antiarrhythmic drug treatment is frequently used as a bridging or
      adjunctive therapy in conjunction with catheter ablation or implantable
      cardioverter defibrillators. Antiarrhythmic agents constitute a very
      heterogeneous group prone to various drug interactions and side-effects.
      Therefore, this article aims to summarise the most important facts and recent
      findings with regard to appropriate contemporary pharmacological therapy of
      atrial and ventricular arrhythmias in clinical practice.

PMID- 16988806
TI  - [Drug therapy for irritable bowel syndrome. What works, what doesn't work and for
      whom?].
AB  - The therapy of patients with irritable bowel syndrome (IBS) is often challenging,
      especially if a broad spectrum of symptoms is present and trigger factors, such
      as the influence of diet or stress, are lacking. Current pathogenetic concepts
      propose central or peripheral alterations that cause disturbed gastrointestinal
      function (motility, visceral sensitivity) and subsequent symptoms. These
      alterations are possibly related to psychological (stress, depression, anxiety)
      and biological (post-infectious residuals, micro-inflammation) influences. Since
      no universally effective medical treatment is available to treat the causes of
      the disease, standard medical therapy is symptom directed (especially for pain,
      constipation and diarrhoea). In addition to well established drugs (like
      spasmolytics, opioids and laxatives), newly developed compounds including those
      with other primarily indications (e.g. antidepressants) are available for highly
      differentiated individualized therapies. New medical approaches which are
      currently undergoing evaluation, promise further progress in the treatment of
      IBS.

PMID- 16988807
TI  - Duodenal diverticulitis: CT and MR findings.
AB  - We report a case of duodenal diverticulitis and describe the helical computed
      tomography and contrast-enhanced magnetic resonance imaging (MRI) study findings.
      Due to its uncommon appearance, this lesion is not typically included in the
      differential diagnosis of pancreatitis or cholecystitis. The imaging findings of
      duodenal diverticulitis can be very suggestive of its diagnosis or can narrow the
      differential diagnosis. To our knowledge and in spite of the wide use of MRI, the
      contrast-enhanced MRI features of this entity, as described below, have not yet
      been reported in the literature.

PMID- 16988808
TI  - Detection of a fusiform coronary artery aneurysm using CT angiography.

PMID- 16988809
TI  - Effect of Epstein-Barr virus infection on global gene expression in
      nasopharyngeal carcinoma.
AB  - It was proposed that Epstein-Barr virus (EBV) is closely associated with
      nasopharyngeal carcinoma (NPC); however, the molecular mechanisms involved in the
      effect of EBV on NPC host genes have not yet been well defined. For this study,
      two sets of microarray experiments, NPC (EBV-free) vs normal epithelial cells and
      EBV(+) vs EBV(-) NPC arrays, were analyzed and the datasets were cross-compared
      to identify any correlation between gene clusters involved in EBV targeting and
      the NPC host gene expression profiles. Statistical analysis revealed that EBV
      seems to have a preference for targeting more genes from the differentially
      expressed group in NPC cells than those from the ubiquitously expressed group.
      Furthermore, this trend is also reflected in log ratios where the EBV target
      genes of the differentially expressed group origin showed greater log ratios than
      genes with an origin from the ubiquitously expressed NPC group. Taken together,
      the genome-wide comparative scanning of EBV and NPC transcriptomes has
      successfully demonstrated that EBV infection has an intensifying effect on the
      signals involved in NPC gene expression both in breadth (the majority of the
      genes) and in depth (greater log ratios).

PMID- 16988810
TI  - Giant cavernous hemangiomas: report of three cases.
AB  - Giant cavernous hemangiomas occur very rarely, and little has been reported about
      their behavior. In this case report three cavernous hemangiomas with a diametric
      measure between 6 cm and 7 cm and distinct features will be described. A 36-year
      old female patient presented with headache and nausea. A CT scan disclosed a
      large circumscribed tumor with strong contrast enhancement in the temporo-parieto
      occipital region of the right cerebral hemisphere and extension into the right
      cerebellar hemisphere. A 35-year-old woman was admitted to our emergency ward
      with a generalized seizure and a dilated pupil. The CT scan showed an extensive
      left frontal lesion containing a substantial hyperintense part, suspicious for
      hemorrhage. A 3-year-old girl was admitted with generalized seizure and
      progressively declining consciousness. A large left frontotemporal
      paraventricular multi-cystic lesion was encountered on the CT scan. All three
      patients were operated on. Two recovered very well. In the case of the 3-year-old
      girl stable disease was reached. Giant cavernomas do not differ from average
      sized cavernomas in clinical, surgical or histopathological presentation but may
      differ radiologically. However, the possible diagnosis of cavernoma can be
      overlooked, due to their size and possible differential diagnosis.

PMID- 16988811
TI  - Constitutive expression of human angiostatin in Pichia pastoris by high-density
      cell culture.
AB  - A high-density cell culture method to produce human angiostatin has been
      successfully established by constitutive expression of the protein in Pichia
      pastoris. The fermentation was carried out in a 20 l bioreactor with a 10 l
      working volume, using a high-density cell culture method by continuously feeding
      with 50% glycerol-0.8% PTM4 to the growing culture for 60 h at 30 degrees C.
      Dissolved oxygen level was maintained at 25-30% and pH was controlled at 5 by the
      addition of 7 M NH4OH. Angiostatin was constitutively expressed during the
      fermentation by linking its expression to the P. pastoris constitutive GAP
      promoter (pGAP). But after 36 h of fermentation, the peak biomass growth was 305
      as measured by absorption of 600 nm, while the peak angiostatin expression was
      176 mg/l. Similar to the product expressed from inducible system [24],
      angiostatin produced from constitutive system also inhibited the angiogenesis on
      the CAM and suppressed the growth of B16 melanoma in C57BL/6J mouse. The above
      results suggest that GAP promoter is more efficient than AOX1 promoter for the
      expression of angiostatin in P. pastoris by shake flask culture or high-density
      cell fermentation and is likely to be an alternative to AOX1 promoter in large
      scale expression of angiostatin and other heterologous proteins.

PMID- 16988812
TI  - A hierarchical model of operational anticipation windows in driving an
      automobile.
AB  - Driving an automobile is an example of a goal-directed activity with high
      complexity in which different behavioral elements have to be integrated and
      brought into a sequential order. On the basis of the reafference principle and
      experimental results on temporal perception and cognitive control, we propose a
      hierarchical model of driving behavior, which can also be adapted to other goal
      directed activities. Driving is conceived of as being controlled by anticipatory
      neuronal programs; if these programs are disrupted by unpredictable stimuli,
      which require an instantaneous reaction, behavioral control returns after
      completion of the reactive mode to the anticipatory mode of driving. In the model
      different levels of anticipation windows are distinguished which, however, are
      interconnected, in a bi-directional way: (a) Strategic level with a
      representation of the driving activity from the beginning to reaching the final
      goal; (b) Segmented tactical level with the sequence of necessary milestones to
      reach the goal; (c) Maneuver level where actions like passing another car or
      keeping a lane are controlled; (d) Short-term integration level of a few seconds
      which allows immediate anticipations; and (e) Synchronization level for
      sensorimotor control and complexity reduction within neuronal assemblies. A flow
      diagram schematically describes different driving situations stressing the
      anticipatory mode of control. In a pilot experiment with 20 subjects using a
      virtual driving situation in a car simulator predictions of the model could be
      verified, i.e., subjects showed a significant preference for the anticipatory
      mode of driving.

PMID- 16988813
TI  - On Fever, famine, and war--but mostly fever.

PMID- 16988814
TI  - Lessons from SARS: control of acute lung failure by the SARS receptor ACE2.
AB  - Angiotensin-converting enzyme 2 (ACE2), a second angiotensin-converting enzyme
      (ACE), regulates the renin-angiotensin system by counterbalancing ACE activity.
      Accumulating evidence in recent years has demonstrated a physiological and
      pathological role of ACE2 in the cardiovascular systems. Recently, it has been
      shown that severe acute respiratory syndrome (SARS) coronavirus, the cause of
      SARS, utilizes ACE2 as an essential receptor for cell fusion and in vivo
      infections in mice. Intriguingly, ACE2 acts as a protective factor in various
      experimental models of acute lung failure and, therefore, acts not only as a key
      determinant for SARS virus entry into cells but also contributes to SARS
      pathogenesis. Here we review the role of ACE2 in disease pathogenesis, including
      lung diseases and cardiovascular diseases.

PMID- 16988815
TI  - Complementation of the pina (null) allele with the wild type Pina sequence
      restores a soft phenotype in transgenic wheat.
AB  - The tightly linked puroindoline genes, Pina and Pinb, control grain texture in
      wheat, with wild type forms of both giving soft, and a sequence alteration
      affecting protein expression or function in either giving rise to hard wheat.
      Previous experiments have shown that addition of wild type Pina in the presence
      of mutated Pinb gave intermediate grain texture but addition of wild type Pinb
      gave soft grain. This raises questions as to whether Pina may be less functional
      than Pinb. Our goal here was to develop and characterize wheat lines expressing
      the wild type Pina-D1a sequence in hard wheat with the null mutation (Pina-D1b)
      for Pina. Three transgenic lines plus Bobwhite were evaluated in two
      environments. Grain texture, grain protein, and kernel weight were determined for
      the transgenic lines and Bobwhite. The three transgenic lines had soft phenotype,
      and none of the transgenic lines differed from Bobwhite for grain protein or
      kernel weight. The soft phenotype was accompanied by increases in Pina transcript
      accumulation. Total Triton X-114 extractable PINA and PINB increased from 2.5 to
      5.5 times those from a soft wheat reference sample, and friabilin, PINA and PINB
      bound to starch, increased from 3.8 to 7.8 times those of the soft wheat
      reference. Bobwhite showed no starch bound PINA, but transgenic lines had levels
      from 5.3 to 13.7 times those of the soft wheat reference sample. Starch bound
      PINB in transgenic lines also increased from 0.9 to 2.5 times that for the soft
      wheat reference sample. The transgenic expression of wild type Pina sequence in
      the Pina null genotype gave soft grain with the characteristics of soft wheat
      including increased starch bound friabilin. The results support the hypothesis
      that both wild type Pin genes need to be present for friabilin formation and soft
      grain.

PMID- 16988816
TI  - Segregation distortion in Arabidopsis C24/Col-0 and Col-0/C24 recombinant inbred
      line populations is due to reduced fertility caused by epistatic interaction of
      two loci.
AB  - A new large set of reciprocal recombinant inbred lines (RILs) was created between
      the Arabidopsis accessions Col-0 and C24 for quantitative trait mapping
      approaches, consisting of 209 Col-0 x C24 and 214 C24 x Col-0 F(7 )RI lines.
      Genotyping was performed using 110 evenly distributed framework single nucleotide
      polymorphism markers, yielding a genetic map of 425.70 cM, with an average
      interval of 3.87 cM. Segregation distortion (SD) was observed in several genomic
      regions during the construction of the genetic map. Linkage disequilibrium
      analysis revealed an association between a distorted region at the bottom of
      chromosome V and a non-distorted region on chromosome IV. A detailed analysis of
      the RILs for these two regions showed that an SD occurred when homozygous Col-0
      alleles on chromosome IV coincided with homozygous C24 alleles at the bottom of
      chromosome V. Using nearly isogenic lines segregating for the distorted region we
      confirmed that this genotypic composition leads to reduced fertility and fitness.

PMID- 16988817
TI  - Characterisation of the laccase-encoding gene abr2 of the dihydroxynaphthalene
      like melanin gene cluster of Aspergillus fumigatus.
AB  - Aspergillus fumigatus is an important pathogen of the immunocompromised host.
      Previously, it was shown that the polyketide synthase encoded by the pksP (alb1)
      gene represents a virulence determinant. pksP is part of a gene cluster involved
      in dihydroxynaphthalene (DHN)-like melanin biosynthesis. Because a putative
      laccase-encoding gene (abr2) is also part of the cluster and a laccase was found
      to represent a virulence factor in Cryptococcus neoformans, here, the Abr2
      laccase was characterised. Deletion of the abr2 gene changed the gray-green
      conidial pigment to a brown color and the ornamentation of conidia was reduced
      compared with wild-type conidia. In contrast to the white pksP mutant, the
      susceptibility of the Deltaabr2 mutant against reactive oxygen species (ROS) was
      not increased, suggesting that the intermediate of DHN-like melanin produced up
      to the step catalysed by Abr2 already possesses ROS scavenging activity. In an
      intranasal mouse infection model, the Deltaabr2 mutant strain showed no reduction
      in virulence compared with the wild type. In the Deltaabr2 mutant, overall
      laccase activity was reduced only during sporulation, but not during vegetative
      growth. An abr2p-lacZ gene fusion was expressed during sporulation, but not
      during vegetative growth confirming the pattern of laccase activity due to Abr2.

PMID- 16988818
TI  - Impaired inhibitory oculomotor control in patients with Parkinson's disease.
AB  - A hallmark of voluntary control is the capacity to inhibit or change partially
      prepared responses, an ability thought to be compromised in patients with
      Parkinson's disease (PD). To test this hypothesis in relation to oculomotor
      control, PD patients and age-matched controls performed a redirect task in which
      they were instructed to cancel a partially prepared saccade on some random
      fraction of trials. Using a race model framework, the time it takes to cancel a
      saccade, the target switch reaction time (TSRT), was estimated for PD and control
      subjects. While saccadic reaction times of control and PD subjects were similar,
      the average TSRT in PD subjects was 139 ms, and was significantly greater than
      the TSRT in controls, which was 113 ms. These results support the hypothesis that
      poor voluntary control exhibited by PD patients in a variety of complex behaviors
      may be caused by impaired inhibitory control as a result of basal ganglia
      dysfunction.

PMID- 16988820
TI  - Influence of tactile afferents on the coordination of muscles during a simulated
      precision grip.
AB  - The mechanisms by which the nervous system coordinates multiple muscles for the
      control of finger movements are not well understood. One possibility is that
      groups of muscles may be enlisted into synergies by last-order inputs that
      project across multiple motor nuclei. In this study we investigated the role that
      tactile input might play in coupling together the activities of motor units in
      two muscles involved in generating the precision grip. Cross-correlation analysis
      was used to assess the degree of synchrony in the discharge times of pairs of
      motor units recorded from index-finger and thumb flexor muscles while human
      subjects performed an isometric task that mimicked a precision grip. The
      magnitude of synchrony is thought to reflect the extent to which divergent last
      order inputs provide common synaptic input across motor neurons. Synchrony was
      evaluated under two simulated-gripping conditions: gripping with normal tactile
      input and gripping when tactile input from the digit pads was eliminated by
      applying flexion forces to fittings glued to the finger nails. Synchrony between
      motor units of index finger flexor and thumb flexor muscles, while substantial,
      was not significantly different across the two tactile-input conditions. These
      findings suggest that tactile input is not required to activate the divergent
      last-order inputs that couple together the activities of the index finger and
      thumb flexor muscles during the precision grip.

PMID- 16988819
TI  - The GABAA receptor-mediated recurrent inhibition in ventral compared with dorsal
      CA1 hippocampal region is weaker, decays faster and lasts less.
AB  - Hippocampal functions appear to be segregated along the dorso-ventral axis of the
      structure. Differences at the cellular and local neuronal network level may be
      involved in this functional segregation. In this study the characteristics of CA1
      recurrent inhibition (RI) were measured and compared between dorsal (DH, n = 95)
      and ventral (VH, n = 60) hippocampal slices, using recordings of suprathreshold
      field potentials. RI strength was estimated as the percentile decrease of the
      population spike (PS) amplitude evoked with an orthodromic stimulus (at the
      Schaffer collaterals) when preceded by an antidromic stimulus (at the alveus).
      Varying the interpulse interval (IPI) between the two stimuli, we estimated RI
      duration. Alvear stimulation produced significant PS suppression in both VH and
      DH at every IPI tested, from 10 to 270 ms. Moreover, gradually more oblique DH
      (but not VH) slices displayed increasing RI, which at IPIs < or = 125 ms was
      reversibly abolished by the GABAA receptor antagonist picrotoxin (10 microM). The
      GABAA-mediated RI, measured under the blockade of GABAB receptors, was weaker,
      decayed faster and lasted less in VH compared to DH slices, regardless of the
      slice orientation. Specifically, in VH compared to DH, the PS suppression at 20
      ms was 34.4 +/- 4.5% versus 69.9 +/- 6.5% (P < 0.001), the time constant of RI
      decay was 29 +/- 2.4 versus 87.5 +/- 13.6 ms (P < 0.01) and the duration was 50
      versus 125 ms (P < 0.001). Thus, GABAA-mediated RI may control the CA1 excitatory
      output less effectively in VH compared to DH. The observed dorso-ventral
      differences in RI contribute to the longitudinal diversification of the structure
      and may underlie to some extent the region-specificity of hippocampal functions.

PMID- 16988821
TI  - Balloon-assisted coil embolization of a posterior cerebral artery aneurysm via a
      persistent primitive trigeminal artery: technical note.
AB  - INTRODUCTION: We present a patient with an acutely ruptured, wide-necked aneurysm
      of the left posterior cerebral artery (PCA) treated with Guglielmi detachable
      coils using the remodeling technique. METHODS: Since the left vertebral artery
      was compressed due to a tumor in the cerebellopontine angle and the right
      vertebral artery was hypoplastic, we used a carotid artery approach via a
      persistent primitive trigeminal artery (PPTA) to selectively catheterize the
      aneurysm. RESULTS: The aneurysm was occluded completely. CONCLUSION: To our
      knowledge this is the first case of a wide-necked PCA aneurysm treated via a PPTA
      and using the remodeling technique. In patients with hypoplastic vertebral
      arteries and a PPTA, this approach may represent an alternative for selective
      embolization of posterior circulation aneurysms not amenable to the conventional
      approach.

PMID- 16988822
TI  - Production of cyclopiazonic acid, aflatrem, and aflatoxin by Aspergillus flavus
      is regulated by veA, a gene necessary for sclerotial formation.
AB  - The plant pathogenic fungus Aspergillus flavus produces several types of
      mycotoxins. The most well known are the carcinogenic compounds called aflatoxins.
      In addition, A. flavus produces cyclopiazonic acid and aflatrem mycotoxins,
      contributing to the toxicity of A. flavus infected crops. Cyclopiazonic acid is a
      specific inhibitor of calcium-dependent ATPase in the sarcoplasmic reticulum that
      results in altered cellular Ca++ levels. Aflatrem is a potent tremorgenic
      mycotoxin known to lead to neurological disorders. Previously we showed that a
      gene called veA controls aflatoxin and sclerotial production in A. parasiticus.
      In this study in A. flavus, we show that the veA homolog in A. flavus not only is
      necessary for the production of aflatoxins B1 and B2 and sclerotia, but also
      regulates the synthesis of the mycotoxins cyclopiazonic acid and aflatrem. The A.
      flavus DeltaveA mutant was completely blocked in the production of aflatrem and
      showed greater than twofold decrease in cyclopiazonic acid production. The genes
      involved in the synthesis of cyclopiazonic acid are unknown; however, the
      aflatrem gene cluster has been characterized. Northern hybridization analysis
      showed that veA is required for expression of the A. flavus aflatrem genes atmC,
      atmG, and atmM. This is the first report of a regulatory gene governing the
      production of cyclopiazonic acid and aflatrem mycotoxins.

PMID- 16988824
TI  - Persistent polyclonal B-cell lymphocytosis: a case report.

PMID- 16988823
TI  - Selective identification of HLA-DP4 binding T cell epitopes encoded by the MAGE-A
      gene family.
AB  - Because of the high frequency of HLA-DP4 in the Caucasian population, we have
      selectively delineated HLA-DP4 restricted T cell epitopes in the MAGE-A tumor
      antigens. We identified 12 good binders to HLA-DP4 and investigated the capacity
      of the seven best binders to induce in vitro specific CD4+ T cell lines from HLA
      DP4 healthy donors. We found that the MAGE-A1 90-104 peptide exhibited a high and
      constant frequency of CD4+ T cell precursors in all the six tested donors. The
      MAGE-A1 268-282 peptide was found immunogenic in only two donors but with a high
      precursor frequency. The MAGE-A12 127-141 peptide was T cell stimulating in six
      different donors and induced fewer T cell lines. The peptide-specific T cell
      lines were stimulated by DC loaded with the lysates of cells transfected with
      MAGE-A1 or MAGE-A12, or loaded with the recombinant protein. We also show that
      the immunoreactivity of CD4+ T cell epitopes restricted to the same HLA II
      molecule may vary from one individual to another, as a result of inter-individual
      variations in the CD4+ T cell repertoire.

PMID- 16988825
TI  - Metabolism of trabectedin (ET-743, Yondelis) in patients with advanced cancer.
AB  - PURPOSE: Trabectedin (ET-743, Yondelis) is a novel anti-cancer drug currently
      undergoing phase II-III evaluation, that has shown remarkable activity in pre
      treated patients with soft tissue sarcoma. Despite extensive pharmacokinetic
      studies, the human disposition and metabolism of trabectedin remain largely
      unknown. We aimed to determine the metabolic profile of trabectedin and to
      identify its metabolites in humans. METHODS: We analysed urine and faeces (the
      major excretory route) from eight cancer patients after a 3 or 24 h intravenous
      administration of [14C]trabectedin. Using liquid chromatography with tandem
      quadrupole mass spectrometric detection (LC-MS/MS) and radiochromatography with
      off-line radioactivity detection by liquid scintillation counting (LC-LSC), we
      characterised the metabolic profile in 0-24 h urine and 0-120 h faeces. RESULTS:
      By radiochromatography, a large number of trabectedin metabolites were detected.
      Incubation with beta-glucuronidase indicated the presence of a glucuronide
      metabolite in urine. Trabectedin, ET-745, ET-759A, ETM-259, ETM-217 (all
      available as reference compounds) and a proposed new metabolite coined ET-731
      were detected using LC-MS/MS. The inter-individual differences in
      radiochromatographic profiles were small and did not correlate with polymorphisms
      in drug-metabolising enzymes (CYP2C9, 2C19, 2D6, 2E1, 3A4, GST-M1, P1, T1 and
      UGT1A1 2B15) as determined by genotyping. CONCLUSIONS: Trabectedin is
      metabolically converted to a large number of compounds that are excreted in both
      urine and faeces. In urine and faeces we have confirmed the presence of
      trabectedin, ET-745, ET-759A, ETM-259, ETM-217 and ETM-204. In addition we have
      identified a putative new metabolite designated ET-731. Future studies should be
      aimed at further identification of possible metabolites and assessment of their
      activity.

PMID- 16988826
TI  - Urinary excretion of L-carnitine and its short-chain acetyl-L-carnitine in
      patients undergoing carboplatin treatment.
AB  - PURPOSE: To evaluate the effect of the anti-cancer drug carboplatin on plasma
      concentrations and urinary excretion of L-carnitine (LC) and its main ester,
      acetyl-L-carnitine (ALC), in cancer patients. METHODS: Plasma and urine
      concentrations of LC and ALC from 11 patients on carboplatin therapy (1 h
      intravenous infusion; AUC dose 4.8 +/- 1.1 mg/ml min) in combination with
      docetaxel, paclitaxel or vinorelbine, were determined by high-performance liquid
      chromatography with fluorimetric detection. RESULTS: Before carboplatin therapy,
      the mean +/- SD plasma concentrations of LC and ALC were 47.8 +/- 10.9 and 7.04
      +/- 1.04 nmoles/ml, respectively, and remained constant throughout the entire
      study period. In contrast, urinary excretion of LC and ALC, increased
      significantly during the chemotherapy from 115 +/- 105 to 480 +/- 348
      micromoles/day (P < 0.01) and from 41 +/- 41 to 89 +/- 52 micromoles/day (P <
      0.05) for LC and ALC, respectively, subsequently reverting to normal 6 days after
      the end of chemotherapy. Similarly, the renal clearance of LC and ALC increased
      substantially during chemotherapy from 1.67 +/- 1.43 to 9.05 +/- 9.52 ml/min (P <
      0.05) and from 4.02 +/- 4.51 to 7.97 +/- 5.05 ml/min (P = not significant) for LC
      and ALC, respectively, reverting to normal 6 days after the end of chemotherapy.
      Plasma concentrations and urinary excretion of glucose, phosphate and urea
      nitrogen and creatinine clearance, however, were not affected by carboplatin
      therapy, indicating no impaired kidney function. CONCLUSION: Treatment with
      carboplatin was associated with a marked urinary loss of LC and ALC, most likely
      due to inhibition of carnitine reabsorption in the kidney.

PMID- 16988827
TI  - A model for the evolution of paralog families in genomes.
AB  - We introduce and analyse a simple probabilistic model of genome evolution. It is
      based on three fundamental evolutionary events: gene loss, duplication and
      accumulated change. This is motivated by previous works which consisted in
      fitting the available genomic data into, what is called paralog distributions.
      This formalism is described by a system of infinite number of linear equations.
      We show that this system generates a semigroup of linear operators on the space l
      (1). We prove that size distribution of paralogous gene families in a genome
      converges to the equilibrium as time goes to infinity. Moreover we show that when
      probabilities of gene removal and duplication are close to each other, then the
      resulting distribution is close to logarithmic distribution. Some empirical
      results for yeast genomes are presented.

PMID- 16988828
TI  - Spatial regulation of cytokinesis by the Kin1 and Pom1 kinases in fission yeast.
AB  - Cytokinesis requires a tight spatio-temporal coordination with mitosis to ensure
      proper segregation of the genetic information during cell division. In fission
      yeast, an actomyosin contractile ring is assembled in mitosis and dictates the
      site of cytokinesis. Here we investigated the functions of Kin1 and Pom1, two
      conserved fission yeast kinases, in cell division. We found that kin1Delta is
      synthetically lethal with pom1Delta because double mutant cells fail to spatially
      organize the actomyosin ring during mitosis, leading to aberrant septum synthesis
      and accumulation of post-mitotic nuclei in the same cell compartment. Assembly of
      an Rlc1-GFP ring in the cell center at mitosis is also compromised. Similar
      cytokinetic defects are observed in a tea1Delta kin1Delta mutant. Furthermore,
      aberrant septation and nuclear accumulation are observed in a pom1Delta strain in
      which the Kin1 level is either down or up-regulated. Thus, a tight control of
      Kin1 level is critical for ensuring accurate cell division in a pom1Delta
      background. Since none of the kinases can substitute for each other, Kin1 and
      Pom1 have distinct complementary functions. We show that Kin1 is required for F
      actin polarization in interphase and after completion of mitosis and this
      function may be essential for cytokinesis in a pom1Delta background.

PMID- 16988829
TI  - Expression of the hyp-1 gene in early stages of development of Hypericum
      perforatum L.
AB  - Level of expression of the hyp-1 gene encoding for the phenolic coupling protein
      which is assumed to be involved in conversion of emodin to hypericin in vitro was
      compared in different organs of Hypericum perforatum seedlings in early stage of
      development in order to find out the sites of hypericin biosynthesis. Hypericins
      are accumulated in multicellular dark glands distributed on the aerial parts of
      H. perforatum, however, the site of the final stages of their biosynthesis
      remains unclear. In order to verify biosynthetic capacity of the dark glands, the
      level of expression of the hyp-1 gene in root, stem, shoot apex, intact leaf,
      leaf lamina free of and leaf margins containing dark glands performed by
      quantitative reverse transcription real-time PCR (qRT-PCR) was compared. The
      results did not reveal any significant difference in the level of hyp-1
      expression in the analyzed leaf tissues. Surprisingly, the highest expression
      level was found in roots, which contain neither any dark glands nor more than
      just traces of hypericin. The lowest expression level was found in the plant stem
      and shoot apex. The results may either indicate that the final stages of
      hypericin biosynthesis take place in different plant parts, mainly in roots,
      which are not essentially associated with the dark glands and primarily serve for
      hypericin accumulation or rise a question on the coding function of the
      respective gene in situ.

PMID- 16988830
TI  - In vitro propagation of an endangered medicinal plant Saussurea involucrata Kar.
      et Kir.
AB  - An efficient micropropagation system for Saussurea involucrata Kar. et Kir., an
      endangered Chinese medicinal plant, has been developed. Shoot organogenesis
      occurred from S. involucrata leaf explants inoculated on medium with appropriate
      supplements of plant growth regulators. 66.0% of shoot regeneration frequency and
      5.2 shoots per leaf explant were achieved when cultured on a medium containing 10
      microM 6-benzylaminopurine (BAP) and 2.5 microM 1-naphthaleneacetic acid (NAA).
      Shoot organogenesis was improved further when the leaf explants were pre
      incubated at low temperature, and 80.6% of shoot regeneration frequency was
      recorded with 9.3 shoots per leaf explant at 4 degrees C by 5-day pretreatment
      period. Up to 87.0% of the regenerated shoots formed complete plantlets on a
      medium containing 2.5 microM indole-3-acetic acid (IAA) within 28 days, and 85.2%
      of the regenerated plantlets survived and grew vigorously in greenhouse
      condition. The phytochemical profile of the micropropagated plants was similar to
      that of wild plants. The regeneration protocol developed in this study provides a
      basis for germplasm conservation and for further investigation of medicinally
      active constituents of the elite medicinal plant.

PMID- 16988831
TI  - Surgical lesion of the anterior optic tract abolishes polarotaxis in tethered
      flying locusts, Schistocerca gregaria.
AB  - Many insects can detect the polarization pattern of the blue sky and rely on
      polarization vision for sky compass orientation. In laboratory experiments,
      tethered flying locusts perform periodic changes in flight behavior under a
      slowly rotating polarizer even if one eye is painted black. Anatomical tracing
      studies and intracellular recordings have suggested that the polarization vision
      pathway in the locust brain involves the anterior optic tract and tubercle, the
      lateral accessory lobe, and the central complex of the brain. To investigate
      whether visual pathways through the anterior optic tract mediate polarotaxis in
      the desert locust, we transected the tract on one side and tested polarotaxis (1)
      with both eyes unoccluded and (2) with the eye of the intact hemisphere painted
      black. In the second group of animals, but not in the first group, polarotaxis
      was abolished. Sham operations did not impair polarotaxis. The experiments show
      that the anterior optic tract is an indispensable part of visual pathways
      mediating polarotaxis in the desert locust.

PMID- 16988832
TI  - Marsupial cardiac myosins are similar to those of eutherians in subunit
      composition and in the correlation of their expression with body size.
AB  - Cardiac myosins and their subunit compositions were studied in ten species of
      marsupial mammals. Using native gel electrophoresis, ventricular myosin in
      macropodoids showed three isoforms, V(1), V(2) and V(3), and western blots using
      specific anti-alpha- and anti-beta-cardiac myosin heavy chain (MyHC) antibodies
      showed their MyHC compositions to be alphaalpha, alphabeta and betabeta,
      respectively. Atrial myosin showed alphaalpha MyHC composition but differed from
      V(1) in light chain composition. Small marsupials (Sminthopsis crassicaudata,
      Antechinus stuartii, Antechinus flavipes) showed virtually pure V(1), while the
      larger (1-3 kg) Pseudocheirus peregrinus and Trichosurus vulpecula showed
      virtually pure V(3). The five macropodoids (Bettongia penicillata, Macropus
      eugenii, Wallabia bicolour, M. rufus and M. giganteus), ranging in body mass from
      2 to 66 kg, expressed considerably more alpha-MyHC (22.8%) than expected for
      their body size. These results show that cardiac myosins in marsupial mammals are
      substantially the same as their eutherian counterparts in subunit composition and
      in the correlation of their expression with body size, the latter feature
      underlies the scaling of resting heart rate and cardiac cross-bridge kinetics
      with specific metabolic rate. The data from macropodoids further suggest that
      expression of cardiac myosins in mammals may also be influenced by their
      metabolic scope.

PMID- 16988834
TI  - Choroidal neovascularisation after surgical removal of submacular lipid plaques
      in diabetic maculopathy.
AB  - BACKGROUND: We report a case of choroidal neovascularisation (CNV) that developed
      after surgical removal of submacular lipid plaques secondary to diabetic
      maculopathy. METHODS: A 73-year-old man with diabetic maculopathy underwent
      standard pars plana vitrectomy and surgical removal of the submacular lipid
      plaques. RESULTS: Preoperative visual acuity was 20/200. Funduscopy revealed a
      macular oedema and subretinal lipid plaques at the macula. Nine months after
      surgery visual acuity had dropped to 20/320 and subfoveal CNV was diagnosed by
      fluorescein angiography. Observational management was chosen. At the last
      examination, 27 months after surgery, visual acuity had worsened to 20/500 and a
      CNV scar was seen at the macula. CONCLUSIONS: CNV development should be kept in
      mind as a possible complication of surgical removal of submacular lipid plaques
      in patients with diabetic retinopathy.

PMID- 16988835
TI  - High incidence of antibodies to lens proteins in sera from patients with uveitis.
AB  - BACKGROUND: Uveitis is an intraocular inflammatory disease in which autoimmune
      reactions have been discussed in playing an important role. Many data in this
      respect derived from the animal model of "experimental autoimmune uveitis", where
      several organ-specific autoantigens have been described such as the retinal S
      antigen and the interphotoreceptor retinoid-binding protein. However, their
      diagnostic and pathogenic role in humans has been controversially discussed. In
      recent studies, the possible relevance of betaB1-crystallin, present in lens and
      ciliary body, has been outlined. We, therefore, wanted to analyse whether sera
      from patients with uveitis might contain antibodies to lens proteins METHODS:
      Human lenses from cadaveric eyes were shock frozen, homogenized, and resuspended.
      The resulting suspension (human lens protein fraction--HLPF) was analyzed for
      antigenicity by ELISA and Western blotting with patients' sera. A total of 165
      patients with uveitis, 54 patients with scleritis and episcleritis, 56 patients
      with other eye diseases, and 112 healthy blood donors were studied. RESULTS:
      Twenty-six (49%) of the 53 patients with anterior uveitis, 17 (32%) of the 53
      patients with intermediate uveitis and 7 (22%) of 32 patients with posterior
      uveitis reacted in the ELISA with the HLPF. Antibodies to lens antigens were
      detected in one-third of patients with panuveitis and retinal vasculitis. In
      contrast, only 12% of the healthy blood donors were positive in the ELISA. The
      number of patients with an autoimmune response to alpha-crystallins in Western
      blot predominated in all investigated groups. CONCLUSIONS: These data indicate
      that antibodies to lens proteins occur in a high incidence in sera from patients
      with uveitis. Forty-nine percent of the patients with anterior uveitis and only
      12% of healthy controls were positive in the ELISA. In our groups of patients and
      controls the autoantibodies reacted in the Western blot predominantly with alpha
      crystallin. Further studies are required to analyze in more detail the clinical
      and etiopathogenetic relevance of the antilens antibodies in uveitis.

PMID- 16988836
TI  - Subretinal neovascular membrane associated with type 2a idiopathic juxtafoveolar
      telangiectasis in pseudoxanthoma elasticum.
AB  - BACKGROUND: The objective was to report a case of pseudoxanthoma elasticum
      associated with type 2A idiopathic juxtafoveolar telangiectasis (T2AIJT)
      complicated by bilateral subretinal neovascular membranes (SRNVM). METHODS: The
      right eye with juxtafoveal SRNVM and the left eye with subfoveal SRNVM underwent
      laser photocoagulation and photodynamic therapy respectively. The follow-up
      duration was 48 months. RESULTS: Best corrected visual acuity was 20/32 in both
      eyes at baseline, and 20/32 in the right eye and 20/200 in the left eye at the
      end of the follow-up. Atrophic changes in the retinal pigment epithelium
      developed around the SRNVM treated with photodynamic therapy (PDT). CONCLUSIONS:
      Pseudoxanthoma elasticum may be associated with T2AIJT complicated by bilateral
      SRNVM. Further studies are needed to assess both efficacy and appropriate PDT
      regime in T2AIJT-related SRNVM, especially if associated with other conditions.

PMID- 16988838
TI  - Prostatic ductal adenocarcinoma mimicking villous adenoma of the urethra.

PMID- 16988837
TI  - Presence of functional TLR2 and TLR4 on human adipocytes.
AB  - In addition to the well-known role of adipose tissue in energy metabolism, it has
      recently been demonstrated that this tissue can secrete a large array of
      molecules, including inflammatory cytokines. Furthermore, recent studies suggest
      that adipose cells can behave as immune cells. Therefore, the aim of this study
      was to determine the presence of the two most prominent 'pattern recognition
      receptors' for bacterial and fungal cell wall components, TLR2 and TLR4 on human
      adipose cells, as well as to assess their functionality. We demonstrated that
      TLR2 and TLR4 were expressed at relatively high levels (compared to a monocyte
      cell line) on the surface of human adipose cells. Stimulation of human adipocytes
      with lipopolysaccharide (LPS), or with lipoteichoic acid (LTA), two specific
      ligands of TLR4 and TLR2, respectively, induced a strong increase in TNFalpha
      production. The specificity of the response was demonstrated by the use of anti
      TLR4 and anti-TLR2 blocking antibodies, which were able to decrease LPS- or LTA
      induced TNFalpha secretion. Thus, it is clear that these receptors are functional
      in human adipocytes. This study adds weight to the argument that human fat tissue
      plays a potential role in innate immunity.

PMID- 16988839
TI  - Primary hepatic lymphoma with spindle cell components: a case report.
AB  - Diffuse large B-cell lymphoma (DLBCL) with spindle cell components is extremely
      rare and often misdiagnosed as carcinoma or sarcoma. Here, we present a case of
      primary DLBCL with spindle cell components arising in the liver, for which a
      preoperative diagnosis by needle biopsies was unsuccessful. The patient was a 70
      year-old man with a continuous cough. Thoracic computed tomography incidentally
      detected a mass of 5 cm in diameter in his liver. The initial and second needle
      biopsies from the liver mass were pathologically diagnosed as suspicious for
      sarcomatoid hepatocellular carcinoma. He underwent an extended left hepatectomy.
      Histological examination revealed a diffuse or epithelioid arrangement of round
      and polygonal cells, mixed with the fascicles of spindle-shaped cells.
      Immunohistochemically, all the morphological types of tumor cells showed positive
      reactions for a lymphocytic marker (CD45RB) and B-cell markers (CD20 and CD79a).
      Double-immunostaining revealed that the spindle-shaped tumor cells expressed
      CD20, but never expressed alpha-smooth muscle actin. Malignant lymphoma with a
      spindle cell morphology is quite uncommon, and this variant can be a diagnostic
      pitfall, especially in tiny biopsy specimens. We emphasize that pathologists
      should be reminded of lymphoma as a differential diagnosis of spindle cell
      tumors.

PMID- 16988841
TI  - Gallium uptake by transferrin and interaction with receptor 1.
AB  - The kinetics and thermodynamics of Ga(III) exchange between gallium
      mononitrilotriacetate and human serum transferrin as well as those of the
      interaction between gallium-loaded transferrin and the transferrin receptor 1
      were investigated in neutral media. Gallium is exchanged between the chelate and
      the C-site of human serum apotransferrin in interaction with bicarbonate in about
      50 s to yield an intermediate complex with an equilibrium constant K (1) = (3.9
      +/- 1.2) x 10(-2), a direct second-order rate constant k (1) = 425 +/- 50 M(-1)
      s(-1) and a reverse second-order rate constant k (-1) = (1.1 +/- 3) x 10(4) M(-1)
      s(-1). The intermediate complex loses a single proton with proton dissociation
      constant K (1a) = 80 +/- 40 nM to yield a first kinetic product. This product
      then undergoes a modification in its conformation which lasts about 500 s to
      produce a second kinetic intermediate, which in turn undergoes a final extremely
      slow (several hours) modification in its conformation to yield the gallium
      saturated transferrin in its final state. The mechanism of gallium uptake differs
      from that of iron and does not involve the same transitions in conformation
      reported during iron uptake. The interaction of gallium-loaded transferrin with
      the transferrin receptor occurs in a single very fast kinetic step with a
      dissociation constant K (d) = 1.10 +/- 0.12 microM and a second-order rate
      constant k (d) = (1.15 +/- 0.3) x 10(10) M(-1) s(-1). This mechanism is different
      from that observed with the ferric holotransferrin and suggests that the
      interaction between the receptor and gallium-loaded transferrin probably takes
      place on the helical domain of the receptor which is specific for the C-site of
      transferrin and HFE. The relevance of gallium incorporation by the transferrin
      receptor-mediated iron-acquisition pathway is discussed.

PMID- 16988842
TI  - [Urology roadmap. New mentoring program for young urologists].

PMID- 16988840
TI  - Analysis of p53 and Bak gene mutations in lymphoproliferative disorders
      developing in rheumatoid arthritis.
AB  - PURPOSE: Individuals affected by rheumatoid arthritis (RA) occasionally develop
      lymphoproliferative disorders (RA-LPD). To study the molecular changes
      underscoring the RA-LPD, mutations of p53 and Bak gene were analyzed in RA-LPD
      with (MTX-LPD) or without methotrexate treatment for RA (non-MTX-LPD). METHODS:
      Histology and immunophenotype were immunohistochemically examined in 32 cases of
      MTX-LPD and 21 of non-MTX-LPD. Polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) followed by direct sequencing was employed
      to detect the mutations of p53 and Bak gene. RESULTS: Frequency of p53 mutations
      in non-MTX-LPD (47.6%) was significantly higher than that in MTX-LPD (15.6%) (P <
      0.05). Among the cases with non-Hodgkin's lymphoma (NHL), the largest category of
      RA-LPD, the frequency of p53 mutations in the non-MTX-NHL (47.6%) was
      significantly higher than that in the MTX-NHL (14.8%) (P < 0.05). Interval
      between the onset of RA and LPD development was significantly longer in LPD with
      p53 gene mutations (median 228 months) than that without mutations (133 months).
      LPD with p53 gene mutations had more advanced diseases and an unfavorable
      prognosis than those without mutations. CONCLUSIONS: MTX-LPD and non-MTX-LPD show
      similar findings in clinical characteristics, histology, EBV positive rate, and
      frequency of Bak gene mutations. Whereas the non-MTX-LPD is distinct from the MTX
      LPD in its significantly higher p53 mutation frequency.

PMID- 16988843
TI  - [Functional results after anatomically successful surgery for stage III/IV
      macular hole].
AB  - PURPOSE: To report the functional results after anatomically successful surgery
      for stage III/IV macular hole. METHODS: Follow-up examinations (ETDRS charts,
      Birkhauser near visual acuity charts, OCT) were carried out in 29 patients 11+/-5
      months after surgery for stage III/IV macular hole (hole size >400 microm); in
      all cases the foveal contour had been restored postoperatively . The surgery
      performed also included cataract surgery (n=26), vitrectomy, ICG-assisted ILM
      peeling (in which perfluorcarbon liquid was used to prevent ICG from coming in
      contact with the retinal pigment epithelium) and tamponade with intraocular gas
      (n=16) or silicone oil (n=13). Silicone oil had been removed by the time of the
      follow-up evaluation. RESULTS: Preoperative mean BCVA was 0.2 (0.64 logMAR+/
      0.24) and postoperative BCVA, 0.5 (0.3 logMAR+/-0.19). None of the patients
      experienced any deterioration in sight; the average improvement in visual acuity
      was 3.5+/-2 lines. In 70% (n=20) of the patients the postoperative BCVA was > or
      =0.5. Visual acuity for near sight was 0.45+/-0.2. In 66% (n=19) a visual acuity
      of > or =0.4 was achieved for close work. The improvement in visual acuity was
      not related to the kind of endotamponade or to the size of the macular hole.
      Patients with macular hole diameters of 400-800 microm (n=20) gained 3.5+/-2.,4
      lines, while in patients with macular hole diameters of 800-1135 microm the
      average gain was 3.6+/-1.3 lines. CONCLUSIONS: Anatomically successful macular
      hole stage III/IV surgery with ICG-assisted ILM peeling and protection of the
      retinal pigment epithelium from contact with ICG by perfluorcarbon liquid can
      yield good functional results.

PMID- 16988844
TI  - [Diagnosis of supranuclear eye movement disorders. Part I: different types of eye
      movements].
AB  - The hallmark of a supranuclear eye movement disorder is a functional impairment
      of one or several types of different eye movements while other types of eye
      movements still work. All eye movement information is conveyed via the nuclei of
      the eye muscle nerves. However, the information for a specific type of eye
      movement is generated in prenuclear cortical and subcortical areas which are
      activated depending on the type of eye movement performed. Knowledge about the
      anatomy of these areas enables us to make a clinical diagnosis or to localize the
      pathological process to a specific area in many neurological conditions.
      Examination of eye movements are thus a valuable clinical tool in many
      neurological and neuroophthalmological diseases. The first part of this two-part
      contribution presents the different types of eye movements, the concept of neural
      integration, and prenuclear structures important for horizontal eye movement as
      well as the pertinent pathology. The second part will appear in the next issue
      and deals with the cerebral structures that are relevant for vertical eye
      movements including their pathology.

PMID- 16988845
TI  - [Radial optic neurotomy: efficacy monitoring using venous ophthalmodynamometry].
AB  - BACKGROUND: Retinal central venous outflow pressure (VOP) can be measured with a
      new ophthalmodynamometer (Meditron, Volklingen, Germany). Radial optic neurotomy
      (RON) is a new surgical approach for central retinal vein occlusion (CRVO) which
      is still controversially discussed. Particularly the early formation of
      retinochoroidal collaterals is intended to achieve normalization of the
      preoperatively increased pressure in the central retinal vein. We investigated
      the VOP after RON. PATIENTS AND METHODS: In total, 21 eyes of 21 patients (9
      male, 12 female) suffering from CRVO were treated by RON. Pars plana vitrectomy
      with nasal radial optic neurotomy and peeling of the internal limiting membrane
      were performed. The mean follow-up time was 10.8 months (6-24 months). Central
      venous outflow pressure was measured using ophthalmodynamometry. RESULTS: The
      most frequent concomitant ophthalmic disease was glaucoma (52%), and the
      predominantly associated systemic disease was hypertension (81%). After RON in 16
      eyes (76%) visual acuity improved by at least 2 lines; in 3 eyes (14%) visual
      acuity was unchanged (+/-1 line) and in 2 patients (10%) visual acuity decreased
      by 2 or more lines. Eyes with visual improvement and formation of chorioretinal
      anastomosis postoperatively showed a significantly lower venous outflow pressure
      assessed with ophthalmodynamometry.

PMID- 16988846
TI  - [Erosive intervertebral joint lesions. A case of pigmented villonodular
      synovitis].
AB  - Pigmented villonodular synovitis (PVNS) is a rare proliferative lesion that can
      affect synovial membranes, tendon sheaths, and bursae. It is usually a
      monarticular disease of the lower extremities, and so far fewer than 30 cases of
      spinal involvement have been reported in the literature. We describe a patient
      with progressive lumbar pain and spinal claudication, in whom a CT scan of the
      lumbar spine revealed destruction fo facet joints L3 to L5. An open biopsy was
      performed, which led to the diagnosis fo PVNS. The patient underwent successful
      surgical resection of the tumour mass and stabilization of segments L3 to S1. Two
      years after surgery the patient has no signs of recurrence. Differential
      diagnosis of erosive vertebral joint disease is discussed.

PMID- 16988847
TI  - [Imaging in rheumatology. Degenerative diseases of the spine].
AB  - Degeneration of the spine is a common reason for pain in the musculoskeletal
      system. Radiography is an important tool for diagnosis and differential
      diagnosis. Cost efficacy and economy of time are advantages in using conventional
      x-rays. Although narrowing of intervertebral disc spaces, irregular ossification
      of the vertebral end-plate as well as osteophytes, facet joint osteoarthritis and
      spondylolisthesis can be observed, early changes in the discs or the subdiscal
      bone can not be detected by x-rays. Moreover, 3-dimensional imaging is not
      possible. Computer tomography (CT) and magnetic resonance imaging (MRI) are
      reliable for identifying disorders of the spine and soft-tissue. Differentiation
      between inflammation, trauma and tumor is possible. There is still a problem with
      the relationship between the information obtained by x-rays or MRI and clinical
      symptoms. Therefore, interpretation of radiological examinations assumes a
      knowledge of clinical symptoms and the different kinds of diseases which are
      possible.

PMID- 16988848
TI  - [Comorbidity in rheumatoid arthritis of early onset. Effects on outcome
      parameters].
AB  - Three-year follow-up data of 1,032 patients with recent onset rheumatoid
      arthritis (RA) were analyzed regarding the frequency of 21 common comorbid
      chronic conditions and their impact on health outcome (i.e., pain, functional
      capacity, disease activity, and radiographic joint damage). Multivariate logistic
      regression analyses were used to calculate age- and gender-adjusted odds ratios
      for each chronic condition on severe functional capacity (<60% of full function).
      Comorbidity was already common at the onset of RA, with 72% of the patients
      having at least one comorbid condition and almost 50% having at least two. Common
      comorbidities were associated with significantly worse baseline measures in at
      least three of seven investigated outcome parameters. The more of these
      conditions patients had, the worse their 3-year outcome. Functional capacity was
      most sensitive to comorbid conditions. In logistic regression, obesity,
      hypercholesterolemia, type II diabetes, and osteoporosis resulted in a twofold
      risk of severe functional limitation (<60% of full function), independent of each
      other and of age and gender. The impact of comorbidity on measures of disease
      severity should be considered when used to compare outcome parameters of
      different RA samples.

PMID- 16988850
TI  - Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs.
      botulinum toxin alone for medically resistant chronic anal fissure: overall poor
      healing rates.
AB  - PURPOSE: This study was designed to assess whether addition of glyceryl
      trinitrate to botulinum toxin improves the healing rate of glyceryl trinitrate
      resistant fissures over that achieved with botulinum toxin alone. METHODS:
      Patients were randomized between botulinum toxin plus glyceryl trinitrate (Group
      A) and botulinum toxin plus placebo paste (Group B). Patients were seen at
      baseline, four and eight weeks, and six months. The primary end point was fissure
      healing at eight weeks. Secondary end points were symptomatic relief, need for
      surgery, side effects, and reduction in maximum resting and squeeze pressures.
      RESULTS: Thirty patients were randomized. Two-thirds of patients had maximum anal
      resting pressures below or within the normal range at entry to the study. Healing
      rates in both treatment groups were disappointing. There was a nonsignificant
      trend to better outcomes in Group A compared with Group B in terms of fissure
      healing (47 vs. 27 percent), symptomatic improvement (87 vs. 67 percent), and
      resort to surgery (27 vs. 47 percent). CONCLUSIONS: There is some evidence to
      suggest that combining glyceryl trinitrate with botulinum toxin is superior to
      the use of botulinum toxin alone for glyceryl trinitrate-resistant anal fissure.
      The poor healing rate may reflect the fact that many of the patients did not have
      significant anal spasm at trial entry.

PMID- 16988851
TI  - Preoperative chemoradiotherapy with concomitant small field boost irradiation for
      locally advanced rectal cancer: a multi-institutional phase II study (KROG 04
      01).
AB  - PURPOSE: This study was designed to determine the effect of concomitant small
      field boost irradiation given during preoperative chemoradiotherapy for patients
      with locally advanced rectal cancer. METHODS: The study prospectively enrolled 38
      patients scheduled for preoperative chemoradiotherapy. Pelvic radiotherapy of
      43.2 Gy/24 fractions was delivered and boost radiotherapy of 7.2 Gy/12 fractions
      was concomitantly administered during the latter half of the pelvic radiotherapy
      treatment period. Two cycles of a bolus 5-fluorouracil and leucovorin injection
      in the first and fifth weeks of radiotherapy were administered. The median time
      to surgery after completion of chemoradiotherapy was six weeks. Tumor responses
      to chemoradiotherapy were assessed by using magnetic resonance volumetry and post
      chemoradiotherapy pathology tests to determine tumor downstaging and tumor
      regression rate. RESULTS: Thirty-six of 38 patients (94.7 percent) underwent the
      scheduled surgery. The mean tumor volume reduction rate was 70.3 percent, and the
      clinical response rate was 66.7 percent. The downstaging rates were 41.7 percent
      for T classification, 85.2 percent for N classification, and 72.2 percent for
      stage. Tumor regression grades after preoperative chemoradiotherapy were Grade 1
      in 5 patients (13.9 percent), Grade 2 in 24 patients (66.7 percent), Grade 3 in 3
      patients (8.3 percent), and Grade 4 in 4 patients (11.1 percent). Ten patients
      (26.3 percent) experienced > or = Grade 3 acute toxicity. CONCLUSIONS: Our data
      suggest that concomitant boost irradiation does not improve clinical outcomes
      compared with other published preoperative chemoradiotherapy regimens. In
      addition, the clinicians choosing to use concomitant small field boost
      irradiation should be cautious to minimize the risk of unplanned sphincter
      ablation.

PMID- 16988852
TI  - Botulinum toxin and hemorrhoids.

PMID- 16988853
TI  - Outcome of metastatic colorectal cancer: analysis of a consecutive series of 229
      patients. The impact of a multidisciplinary approach.
AB  - PURPOSE: New chemotherapy agents and integrated treatments have improved the
      prognosis of patients with metastatic colorectal cancer. METHODS: From January
      2000 to December 2002, 229 consecutive metastatic patients were prospectively
      followed and their outcomes were analyzed. They were divided initially into four
      treatment groups: A, palliative chemotherapy for extensive extrahepatic disease
      with or without hepatic disease (97 patients); B, palliative chemotherapy as in
      Group A for extensive hepatic disease unlikely to become resectable (36
      patients); C, neoadjuvant chemotherapy for potentially resectable liver
      metastases if responsive to therapy (33 patients); D, immediate surgery for liver
      metastases (63 patients). RESULTS: The series was analyzed after a median follow
      up of 22.6 months. The median progression-free survival was 9, 7.3, 11.5, and 26
      months in Groups A, B, C, and D, respectively. The median overall survival was
      20.1, 17.2, 24.8, and >48 months in Groups A, B, C, and D, respectively. The
      outcome was considered for the 69 patients with metastases confined to the liver
      (Groups B and C), who were treated initially with chemotherapy. Surgery was
      performed in 21 patients (5 from Group B, and 16 from Group C) and was R0 in 16.
      In resected patients, the median progression-free survival was 14.7 months and
      the median overall survival was 40.5 months. In unresected patients, the median
      progression-free survival was 7.6 months and the median overall survival was 17.5
      months. CONCLUSIONS: Neoadjuvant therapy may prolong overall survival in a subset
      of patients with multiple hepatic metastases. The global impact on progression
      free survival is low; less than one-half of the patients resected after
      chemotherapy are disease-free at three years. However, patients resected after
      chemotherapy obtained overall survival similar to that of primary surgery,
      suggesting a positive role for integrated approaches.

PMID- 16988854
TI  - Three-dimensional anal endosonography may improve detection of recurrent anal
      cancer.
AB  - PURPOSE: In our center since 2001, follow-up examination has included three
      dimensional endosonography in all patients with suspicion of local recurrence of
      anal cancer. This study was designed to investigate whether three-dimensional
      endosonography surpassed two-dimensional endosonography as a diagnostic tool for
      patients with suspected local recurrence. METHODS: This prospective study
      included 38 consecutive patients who have had anal carcinoma and were
      investigated using three-dimensional endosonography in combination with anoscopy
      and digital rectal examination at Rigshospitalet from July 2001 to January 2005
      under suspicion of local recurrence. All endosonographic examinations-two
      dimensional, three-dimensional, and three-dimensional in combination with
      anoscopy and digital rectal examination-were evaluated by blinded observers. The
      observers scored each examination according to a five-point scale in which a
      score from 1 to 3 was regarded as benign endosonographic findings and a score
      from 4 to 5 was regarded as malignant endosonographic findings. The
      endosonographic diagnosis for each examination was compared with histologic
      evaluation or when no biopsy had been taken with a follow-up period of at least
      six months. If a patient showed no signs of local recurrence in the follow-up
      period, no local recurrence was considered to be present at the time of the
      investigation. RESULTS: The sensitivity was 1.0 for three-dimensional
      endosonography in combination with palpation, 0.86 for three-dimensional
      endosonography alone, and 0.57 for two-dimensional endosonography. The
      differences between two-dimensional endosonography and three-dimensional
      endosonography alone as well as two-dimensional endosonography and three
      dimensional endosonography + anoscopy and digital rectal examination both reached
      significance with P values <0.05. CONCLUSIONS: This study indicates that three
      dimensional endosonography surpasses two-dimensional endosonography in the
      evaluation of patients with suspicion of local recurrence of anal cancer
      especially in combination with anoscopy and digital rectal examination.

PMID- 16988855
TI  - Anaerobic meningitis secondary to a rectothecal fistula arising from an anterior
      sacral meningocele: report of a case and review of the literature.
AB  - An anterior sacral meningocele is a diverticulum of the thecal sac protruding
      anteriorly from the sacral spinal canal into the extraperitoneal presacral space.
      It is a rare congenital anomaly comprising of a thin wall of fibrous connective
      tissue, and containing cerebrospinal fluid and, occasionally, adjacent nerve
      fibers. We report an unusual case of a 48-year-old male who presented with
      meningitis secondary to a rectothecal fistula arising from an anterior sacral
      meningocele.

PMID- 16988856
TI  - Percutaneous CT scan-guided drainage vs. antibiotherapy alone for Hinchey II
      diverticulitis: a case-control study.
AB  - PURPOSE: CT-scan-guided percutaneous abscess drainage of Hinchey Stage II
      diverticulitis is considered the best initial approach to treat conservatively
      the abscess and to subsequently perform an elective sigmoidectomy. However,
      drainage is not always technically feasible, may expose the patient to additional
      morbidity, and has not been critically evaluated in this indication. This study
      was undertaken to compare the results of percutaneous drainage vs. antibiotic
      therapy alone in patients with Hinchey II diverticulitis. METHODS: This was a
      case-control study of all patients who presented in our institution with Hinchey
      Stage II diverticulitis between 1993 and 2005. Thirty-four patients underwent
      abscess drainage under CT-scan guidance (Group 1), and 32 patients were treated
      with antibiotic therapy alone (Group 2), in most cases because CT-scan-guided
      abscess drainage was considered technically unfeasible by the interventional
      radiology team. Initial conservative treatment was considered a failure when: 1)
      emergency surgery had to be performed, 2) signs of worsening sepsis developed,
      and 3) abscess recurred within four weeks of drainage. RESULTS: The median size
      of abscess was 6 (range, 3-18) cm in Group 1 and 4 (range, 3-10) cm in Group 2 (P
      = 0.002). Median duration of drainage was 8 (range, 1-18) days. Conservative
      treatment failed in 11 patients (33 percent) of Group 1, and in 6 patients (19
      percent) of Group 2 (P = 0.26). Ten patients (29 percent) in Group 1 and five
      patients (16 percent) in Group 2 underwent emergency surgery (P = 0.24); there
      were four postoperative deaths (26.6 percent) in this subgroup. Twelve patients
      (35 percent) in Group 1 and 16 patients (50 percent) in Group 2 subsequently
      underwent an elective sigmoid resection (P = 0.31). In this subgroup of patients,
      there was neither anastomotic leakage nor postoperative death. CONCLUSIONS:
      Emergency surgery for Hinchey Stage II diverticulitis carries a high mortality
      rate and should be avoided. To achieve this, antibiotic therapy alone seems to be
      a safe alternative, whenever percutaneous drainage is technically difficult or
      hazardous. Actually, our data did not demonstrate any benefit of CT scan-guided
      percutaneous abscess drainage, suggesting that the role of interventional
      radiology techniques in this indication deserves further critical evaluation.

PMID- 16988859
TI  - Lack of threshold for anisotonic cell volume regulation.
AB  - Most cells possess mechanisms that are able to detect cellular volume shifts and
      to signal the initiation of appropriate volume regulatory responses. However, the
      identity and characteristics of the detecting mechanism remain obscure. In this
      study, we explored the influence of hypertonic and hypotonic challenges of
      varying magnitude on the characteristics of the ensuing regulatory volume
      increase (RVI) and regulatory volume decrease (RVD) of cultured bovine corneal
      endothelial cells (CBCECs). The main question we asked was whether a threshold of
      stimulation existed that would unleash a regulatory response. CBCECs (passage 1
      3) were seeded on rectangular glass coverslips and grown for 1-2 days. We used a
      procedure based on detection of light scattering to monitor the transient volume
      changes of such plated cells when subjected to osmotic challenge. The osmometric
      responses were asymmetric: cells shrank faster than they swelled (by a factor of
      3). Complete volume regulatory responses took 10-12 min. Bumetanide (50 microM)
      resulted in incomplete (50%) RVI. We found no threshold as the cells examined
      responded to hypertonic and hypotonic stimuli as low as 1%. There was some
      gradation as stimuli of <4% resulted in incomplete volume regulation. The degree
      of activation of the volume responses grew as an exponential buildup with the
      strength of the anisotonic challenge. We discuss how our observations are
      consistent with volume sensing mechanisms based on both ionic strength and the
      cytoskeleton.

PMID- 16988860
TI  - Guanosine 5'-[gamma-thio]triphosphate-mediated activation of cytosol
      phospholipase C caused lysosomal destabilization.
AB  - Lysosomal disintegration is critical for the organelle functions and cellular
      viability. In this study, we established that guanosine 5'-[gamma
      thio]triphosphate (GTP-gamma-S)-activated cytosol of rat hepatocytes could
      increase lysosomal permeability to both potassium ions and protons and
      osmotically destabilize the lysosomes via K(+)/H(+) exchange. These results were
      obtained through measurements of lysosomal beta-hexosaminidase-free activity,
      membrane potential and intralysosomal pH. Assays of phospholipase C (PLC)
      activity show that cytosolic PLC was activated upon addition of GTP-gamma-S to
      the cytosol. The effects of cytosol on the lysosomes could be abolished by D609,
      an inhibitor of PLC, but not by the inhibitors of phospholipase A(2). The cytosol
      treated lysosomes disintegrated markedly in hypotonic sucrose medium, reflecting
      that the lysosomal osmotic sensitivity increased. Microscopic observations showed
      that the lysosomes became more swollen in hypotonic sucrose medium. This
      indicates that the cytosol treatment induced osmotic shock to the lysosomes and
      an influx of water into the organelle.

PMID- 16988861
TI  - Differential phosphoinositide binding to components of the G protein-gated K+
      channel.
AB  - The regulation of ion channels and transporters by anionic phospholipids is
      currently very topical. G protein-gated K(+) channels from the Kir3.0 family are
      involved in slowing the heart rate, generating late inhibitory postsynaptic
      potentials and controlling hormone release from neuroendocrine cells. There is
      considerable functional precedent for the control of these channels by
      phosphatidylinositol 4,5-bisphosphate. In this study, we used a biochemical assay
      to investigate the lipid binding properties of Kir3.0 channel domains. We reveal
      a differential binding affinity to a range of phosphoinositides between the C
      termini of the Kir3.0 isoforms. Furthermore, the N terminus in addition to the C
      terminus of Kir3.4 is necessary to observe binding and is decreased by the
      mutations R72A, K195A and R196A but not K194A. Protein kinase C phosphorylation
      of the Kir3.1 C-terminal fusion protein decreases anionic phospholipid binding.
      The differential binding affinity has functional consequences as the inhibition
      of homomeric Kir3.1, occurring after M3 receptor activation, recovers over
      minutes while homomeric Kir3.2 does not.

PMID- 16988862
TI  - Hypertonic saline attenuates colonic tumor cell metastatic potential by
      activating transmembrane sodium conductance.
AB  - Hypertonic saline (HTS) suppresses tumor cell-endothelial interactions by
      reducing integrin expression. This translates into reduced adhesion, migration
      and metastatic potential. This study determined the relative contributions of
      hyperosmolarity and sodium-specific hypertonicity on the inhibitory effects of
      HTS, the intracellular pH and sodium responses to HTS and the role of
      cytoskeletal remodeling in these changes. Human colonic tumor cells (LS174T) were
      exposed to lipopolysaccharide under isotonic, hypertonic, sodium-free (N-methyl-D
      glucamine), hyperosmolar (mannitol or urea), disrupted cytoskeletal (10 microg/ml
      cytochalasin D) conditions or in the presence of 5-(N-ethyl-N-isopropyl)amiloride
      (EIPA). Beta(1) integrin expression was measured flow-cytometrically.
      Intracellular sodium and pH were measured with confocal laser microscopic
      imaging. Statistical analysis was performed with analysis of variance, and P <
      0.05 was considered significant. Data are represented as mean +/- SEM. Hypertonic
      exposure attenuated integrin expression (62.03 +/- 4.7% of control, P < 0.04). No
      discernible effect was observed with sodium-free or hyperosmolar solutions. HTS
      evoked a cellular alkalinization (by a mean 0.2 pH units) and an increase in
      cytosolic sodium concentration (by a mean 12.4 mM, P < 0.001) via upregulation of
      sodium-hydrogen exchange. Disassembly of actin microfilaments by cytochalasin D
      and antiporter inhibition with EIPA abrogated the effect of hypertonicity on
      integrin expression and intracellular sodium and pH (P < 0.05). HTS downregulates
      adhesion molecule expression via a hypertonic, sodium-specific, cytoskeletally
      mediated mechanism that involves activation of sodium-hydrogen exchange with
      associated changes in intracellular pH and sodium concentrations.

PMID- 16988863
TI  - A suppressor analysis of residues involved in cation transport in the lactose
      permease: identification of a coupling sensor.
AB  - Four amino acids critical for lactose permease function were altered using site
      directed mutagenesis. The resulting Quad mutant (E269Q/R302L/H322Q/E325Q) was
      expressed at 60% of wild-type levels but found to have negligible transport
      activity. The Quad mutant was used as a parental strain to isolate suppressors
      that regained the ability to ferment the alpha-galactoside melibiose. Six
      different suppressors were identified involving five discrete amino acid changes
      and one amino acid deletion (Q60L, V229G, Y236D, S306L, K319N and DeltaI298). All
      of the suppressors transported alpha-galactosides at substantial rates. In
      addition, the Q60L, DeltaI298 and K319N suppressors regained a small but
      detectable amount of lactose transport. Assays of sugar-driven cation transport
      showed that both the Q60L and K319N suppressors couple the influx of melibiose
      with cations (H(+) or H(3)O(+)). Taken together, the data show that the cation
      binding domain in the lactose permease is not a fixed structure as proposed in
      previous models. Rather, the data are consistent with a model in which several
      ionizable residues form a dynamic coupling sensor that also may interact directly
      with the cation and lactose.

PMID- 16988864
TI  - Dynamics of calcium fluxes in nonexcitable cells: mathematical modeling.
AB  - Mathematical models simulating the dynamics of calcium redistribution (elicited
      by experimental interference with the pathways of calcium fluxes) in cellular
      compartments have been developed, based on a minimal scheme of the pathways of
      calcium fluxes in nonexcitable cells suspended in calcium-free medium. The models
      are consistent with available experimental data. All parameters are
      quantitatively related to the intrinsic properties of calcium adenosine
      triphosphatases (ATPases) and cellular membranes; there is no interdependence
      between the parameters. The models can be used as the basis for quantitative
      analysis and interpretation of experimental data. The activities of plasma
      membrane and sarcoendoplasmic reticulum calcium ATPases (PMCA and SERCAs) are
      governed by different mechanisms. PMCA is likely to undergo transitions from
      inactive to active to "dormant" (not identical to the initial) and back to
      inactive states, the mean duration of the cycle lasting for minutes or longer.
      The sequence of the transitions is initiated, presumably, by an increase in
      cytosolic calcium concentration. The transition of PMCA from inactive to active
      (at least at low rates of increase in cytosolic calcium concentration) is likely
      to be slower than that from active to dormant. SERCA, presumably, transits from
      inactive to active state in response to increases in calcium leakage from calcium
      stores. Whereas PMCA extrudes excess calcium (a definite quantity of it) in a
      short pulse, SERCA retakes calcium back into the stores permanently at a high
      rate. The models presented here may be the best means for the moment to
      quantitatively relate the dynamics of calcium fluxes in nonexcitable cells with
      known or putative properties of the mechanisms underlying activation of calcium
      ATPases.

PMID- 16988865
TI  - Use of steady-state laurdan fluorescence to detect changes in liquid ordered
      phases in human erythrocyte membranes.
AB  - In artificial phospholipid bilayers, dual measurements of laurdan steady-state
      anisotropy and emission spectra can be used to identify the presence of liquid
      ordered phases. Human erythrocytes were used as a model to test whether similar
      measurements could be applied to biological samples. Specifically, laurdan
      anisotropy and emission spectra were obtained from native erythrocytes before and
      after treatment with calcium ionophore and from the microvesicles (known to be
      enriched in liquid ordered domains) shed from the cells during calcium entry.
      Spectral and anisotropy data were consistent with an increased order and reduced
      fluidity of erythrocyte membrane lipids upon ionophore treatment. Microvesicle
      membranes appeared more ordered than native erythrocytes and similar to ionophore
      treated cells based on laurdan emission. In contrast, the anisotropy value was
      lower in microvesicles compared to ionophore-treated cells, suggesting greater
      probe mobility. Parallel measurements of diphenylhexatriene anisotropy
      corroborated the laurdan data. These results were consistent with the liquid
      ordered property of microvesicle membranes based on comparisons to behavior in
      artificial membranes. Two-photon microscopy was used to examine the distribution
      of laurdan fluorescence along the surface of erythrocyte membranes before and
      after ionophore treatment. A dual spatial analysis of laurdan anisotropy, as
      revealed by the distribution of laurdan emission spectra, and intensity excited
      by polarized light suggested that the plasma membranes of ionophore-treated
      erythrocytes may also exhibit elevated numbers of liquid ordered domains.

PMID- 16988866
TI  - Influence of potentially confounding factors on sea urchin porewater toxicity
      tests.
AB  - The influence of potentially confounding factors has been identified as a concern
      for interpreting sea urchin porewater toxicity test data. The results from >40
      sediment-quality assessment surveys using early-life stages of the sea urchin
      Arbacia punctulata were compiled and examined to determine acceptable ranges of
      natural variables such as pH, ammonia, and dissolved organic carbon on the
      fertilization and embryological development endpoints. In addition, laboratory
      experiments were also conducted with A. punctulata and compared with information
      from the literature. Pore water with pH as low as 6.9 is an unlikely contributor
      to toxicity for the fertilization and embryological development tests with A.
      punctulata. Other species of sea urchin have narrower pH tolerance ranges.
      Ammonia is rarely a contributing factor in pore water toxicity tests using the
      fertilization endpoint, but the embryological development endpoint may be
      influenced by ammonia concentrations commonly found in porewater samples.
      Therefore, ammonia needs to be considered when interpreting results for the
      embryological development test. Humic acid does not affect sea urchin
      fertilization at saturation concentrations, but it could have an effect on the
      embryological development endpoint at near-saturation concentrations. There was
      no correlation between sediment total organic carbon concentrations and porewater
      dissolved organic carbon concentrations. Because of the potential for many
      varying substances to activate parthenogenesis in sea urchin eggs, it is
      recommended that a no-sperm control be included with every fertilization test
      treatment.

PMID- 16988867
TI  - Atmospheric deposition of polycyclic aromatic hydrocarbons in an urban and a
      suburban area of Korea from 2002 to 2004.
AB  - Atmospheric bulk samples (wet and dry) were collected monthly during 2002 to 2004
      from an urban and a suburban area in Korea for assessment of depositional flux
      and seasonal variations in the concentrations of polycyclic aromatic hydrocarbons
      (PAHs). PAH depositional flux ranged from 64.1 to 610 microg/m2/y for the urban
      area and from 65 to 460 microg/m2/y for the suburban area. The fluxes of PAHs
      measured in this study were comparable with those reported for urban and suburban
      areas in other countries. The fluxes of particulates and PAHs were higher in
      winter than in summer, consistent with the greater per capita consumption of
      fossil fuel in winter than in summer. Ambient temperature played a major role in
      the seasonal variability in PAH fluxes. Photochemical degradation of PAHs appears
      to occur during the summer months. The relationship of PAH depositional fluxes
      with major air pollutants, such as ozone, sulfur dioxide, carbon monoxide,
      nitrogen dioxide, and presence of particulate matter up to 10 microm in size
      (PM10), was also investigated. Dominant PAH compounds in both the urban and the
      suburban locations were benzo[g,h,i]perylene, pyrene, and indeno[1,2,3
      c,d]pyrene. Based on the PAH diagnostic ratios and a factor analysis, the major
      sources of PAHs in the urban and the suburban regions were found to be similar.
      Diesel exhaust, coal combustion, and gasoline emissions contributed predominantly
      to atmospheric PAH contamination.

PMID- 16988868
TI  - Biomarkers of heavy metal contamination in the red fingered marsh crab,
      Parasesarma erythodactyla.
AB  - Variation in glutathione antioxidant biochemistry in response to metal
      contamination and accumulation under field conditions was examined in the
      brachyurid grapsid, Parasesarma erythodactyla. Significant relationships
      suggesting accumulation were found between sediment metals and metals in crab
      tissue for Pb, Cu, Cr, Zn, and Se in males and Cd, Pb, Cr Zn, As, and Se in
      females. Higher pH and lower organic content were associated with greater uptake
      of selected metals in males and females. Higher salinity was related to increased
      metal uptake for Cu and Zn in males and lower salinities to increased Se uptake
      for males and females. When examining metals, which were elevated in crabs,
      patterns of site discrimination were similar to sediment metal site
      discrimination for both males and females. In terms of biochemical responses,
      glutathione levels remained constant while glutathione peroxidase activity was
      elevated in individuals where metals were elevated. Only females with the highest
      levels of accumulated metals exhibited increases in lipid peroxidation products.
      Glutathione peroxidase activity may be a sensitive biomarker of metal exposure
      and biological effect and lipid peroxides as a secondary marker when accumulated
      metals are high.

PMID- 16988869
TI  - Evaluation of remediation of coal mining wastewater by chitosan microspheres
      using biomarkers.
AB  - Acidic mine waters have a marked influence on the surrounding environment and
      pose a serious threat through long-term environmental degradation. Therefore, it
      is important to improve and monitor water quality with the aim of decreasing the
      hazard presented by this effluent emission. The aim of this work was to evaluate
      the remediation of mining wastewater effluents by chitosan microspheres using
      biomarkers of exposure and effect. DNA damage (Comet assay) and several
      biomarkers of oxidative stress, such as lipoperoxidation levels (TBARS),
      superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST)
      activities, and contents of reduced glutathione (GSH), were measured in blood and
      liver of tilapia (Oreochromis niloticus) exposed for 7, 15, and 30 days to
      dechlorinated tap water, 10% coal mining wastewater (CMW), and coal mining
      wastewater treated with chitosan microspheres (RCM). The results indicate that
      hepatic TBARS levels were significantly higher in fish exposed to CMW after 7,
      15, and 30 days (100%, 86%, and 63%, respectively), and after remediation there
      was no significant difference in relation to the control group. Hepatic GSH
      concentrations were lower than control values for CMW after 7 and 15 days of
      exposure (34% decrease at both times), and this concentration was normalized by
      treatment with chitosan. SOD showed increased activity in liver after 15 and 30
      days of exposure, 30% and 36%, respectively, and in fish exposed to RCM there was
      no change in this activity compared with the control group. Increased CAT
      activity in liver was observed during all experimental periods in fish exposed to
      CMW (46%, 50%, and 56% at 7, 15, and 30 days, respectively) compared with the
      control or treated-water groups. The highest increase in hepatic GST activity
      (106%) was observed only in fish exposed to CMW for 30 days. There was an
      increase in DNA damage in liver (50% at 7 and 15 days) and blood (79%, 77%, and
      48% at 7, 15, and 30 days, respectively) after exposure to CMW. In contrast, the
      fish exposed to wastewater treated with chitosan microspheres exhibited DNA
      fragmentation indexes similar to the control group. The results obtained indicate
      the use of oxidative stress biomarkers as useful tools for the toxicity
      evaluation of coal mining effluents and also suggest that chitosan microspheres
      may be used as an alternative approach for remediation of coal mining
      wastewaters.

PMID- 16988870
TI  - Avian mortality at oil pits in the United States: A review of the problem and
      efforts for its solution.
AB  - Oil production operations produce waste fluids that may be stored in pits, open
      tanks, and other sites accessible to wildlife. Birds visit these fluid-filled
      pits and tanks ("oil pits"), which often resemble water sources, and may become
      trapped and die. The US Fish and Wildlife Service (USFWS) has a program to reduce
      these impacts by locating problem pits, documenting mortality of protected
      wildlife species, and seeking cleanup or corrective action at problem pits with
      the help of state and federal agencies regulating the oil industry. Species
      identification and verification of protected status for birds recovered from oil
      pits are performed at the USFWS National Fish and Wildlife Forensics Laboratory.
      From 1992 to 2005, a minimum of 2060 individual birds were identified from
      remains recovered from oil pits, representing 172 species from 44 families. The
      taxonomic and ecological diversity of these birds indicates that oil pits pose a
      threat to virtually all species of birds that encounter them. Ninety-two percent
      of identified bird remains belonged to protected species. Most remains identified
      at the Forensics Laboratory were from passerines, particularly ground-foraging
      species. Based on Forensics Laboratory and USFWS field data, oil pits currently
      cause the deaths of 500,000-1 million birds per year. Although law enforcement
      and industry efforts have produced genuine progress on this issue, oil pits
      remain a significant source of mortality for birds in the United States.

PMID- 16988871
TI  - Successful intra-arterial thrombolysis for acute ischemic stroke in the immediate
      postpartum period: case report.
AB  - Stroke in pregnancy and the puerperium is a rare but potentially devastating
      event. We present the case of a previously healthy woman who underwent a cesarean
      delivery and experienced a middle cerebral artery thrombosis in the immediate
      postpartum period that was subsequently lysed with intra-arterial urokinase. The
      patient made a complete neurologic recovery. To the best of our knowledge, this
      is the first reported case of successful intra-arterial thrombolysis for ischemic
      stroke in the postpartum period.

PMID- 16988872
TI  - Management of vertebral stenosis complicated by presence of acute thrombus.
AB  - A 44-year-old male presented with multiple punctate acute infarcts of the
      vertebrobasilar circulation and a computed tomographic angiogram showing stenosis
      of the right vertebral origin. A digital subtraction angiogram demonstrated a new
      intraluminal filling defect at the origin of the stenotic vertebral artery where
      antegrade flow was maintained. This filling defect was accepted to be an acute
      thrombus of the vertebral origin, most likely due to rupture of a vulnerable
      plaque. The patient was treated with intravenous heparin. A control angiogram
      revealed dissolution of the acute thrombus under anticoagulation and the patient
      was treated with stenting with distal protection. Diffusion-weighted magnetic
      resonance imaging demonstrated no additional acute ischemic lesions. We were
      unable to find a similar report in the English literature documenting successful
      management of an acute vertebral ostial thrombus with anticoagulation.
      Anticoagulation might be considered prior to endovascular treatment of
      symptomatic vertebral stenoses complicated by the presence of acute thrombus.

PMID- 16988873
TI  - CT findings of ruptured intramural hematoma of the aorta extending along the
      pulmonary artery.
AB  - Mediastinal hematoma extending along the pulmonary artery is a rare complication
      of Stanford type A classic (double-barreled) aortic dissection. Rupture from the
      posterior aspect of the aortic root penetrates the shared adventitia of the aorta
      and pulmonary artery. From this location, hematoma can spread along the
      adventitial planes of the pulmonary arteries out into the lungs. We report a case
      of ruptured intramural hematoma of the aorta (IMH) extending along the pulmonary
      artery. To our knowledge, this finding in patients with IMH has not been reported
      in the literature.

PMID- 16988874
TI  - Comparison of three different needles for percutaneous injections.

PMID- 16988875
TI  - Clinical assessment of percutaneous radiofrequency ablation for painful
      metastatic bone tumors.
AB  - PURPOSE: To investigate the pain-alleviating effects of radiofrequency ablation
      (RFA) on metastatic bone tumors in relation to tumor size, combined therapy, and
      percent tumor necrosis rate following RFA. METHODS: Subjects comprised 24
      patients with 28 painful metastatic bone tumors. A 17G internally cooled
      electrode was inserted into the tumor for CT guidance and ablation was performed.
      Bone cement was injected following RFA for 4 tumors involving a weight-bearing
      bone, while 5 tumors were treated using combined RFA and external irradiation.
      Percent necrosis rate of the tumor was measured using contrast-enhanced computed
      tomography 1 week after RFA. RESULTS: Improvement in the visual analog scale
      (VAS) score was 4.6 +/- 2.2 for large tumors (> 5 cm, n = 12), 3.7 +/- 1.8 for
      medium-sized tumors (3.1-5.0 cm, n = 11), and 3.5 +/- 1.7 for small tumors (< or
      = 3 cm, n = 4), with no significant differences noted among tumor sizes.
      Improvement in the VAS score was 3.5 +/- 1.3 for the 4 tumors in the RFA + bone
      cement group, 3.2 +/- 1.9 for the 5 tumors in the RFA + radiation therapy group,
      and 4.8 +/- 2.2 for the 18 tumors in the RFA group. No significant differences
      were identified between groups. The improvement in the VAS score was 3.8 +/- 2.3,
      4.0 +/- 1.9, and 4.7 +/- 2.6 in patients with tumor necrosis rates of 0-49%, 50
      74%, and 75-100%, respectively. No significant association was observed among
      these three groups. CONCLUSION: Percutaneous RFA therapy was effective in
      relieving pain due to metastatic bone tumors. No relationships appear to exist
      between initial response and tumor size, combined therapy, and percent tumor
      necrosis.

PMID- 16988876
TI  - Superficial temporal artery pseudoaneurysm: a conservative approach in a
      critically ill patient.
AB  - A 71-year-old man affected by cardio- and cerebrovascular disease experienced an
      accidental fall and trauma to the fronto-temporal area of the head. A few weeks
      later a growing mass appeared on his scalp. A diagnosis of superficial temporal
      artery pseudoaneurysm was made following CT and color Doppler ultrasound. His
      clinical condition favoured a conservative approach by ultrasound-guided
      compression and subsequent surgical resection. A conservative approach should be
      considered the treatment of choice in critically ill patients affected by
      superficial temporal artery pseudoaneurysm.

PMID- 16988877
TI  - Cone-beam CT with flat-panel-detector digital angiography system: early
      experience in abdominal interventional procedures.
AB  - We developed a cone-beam computed tomography (CBCT) system equipped with a large
      flat-panel detector. Data obtained by 200 degree rotation imaging are
      reconstructed by means of CBCT to generate three-dimensional images. We report
      the use of CBCT angiography using CBCT in 10 patients with 8 liver malignancies
      and 2 hypersplenisms during abdominal interventional procedures. CBCT was very
      useful for interventional radiologists to confirm a perfusion area of the artery
      catheter wedged on CT by injection of contrast media through the catheter tip,
      although the image quality was slightly degraded, scoring as 2.60 on average by
      streak artifacts. CBCT is space-saving because it does not require a CT system
      with a gantry, and it is also time-saving because it does not require the
      transfer of patients.

PMID- 16988878
TI  - Paravertebral block: an improved method of pain control in percutaneous
      transhepatic biliary drainage.
AB  - BACKGROUND AND PURPOSE: Percutaneous transhepatic biliary drainage remains a
      painful procedure in many cases despite the routine use of large amounts of
      intravenous sedation. We present a feasibility study of thoracic paravertebral
      blocks in an effort to reduce pain during and following the procedure and reduce
      requirements for intravenous sedation. METHODS: Ten consecutive patients
      undergoing biliary drainage procedures received fluoroscopically guided
      paravertebral blocks and then had supplemental intravenous sedation as required
      to maintain patient comfort. Levels T8-T9 and T9-T10 on the right were targeted
      with 10-20 ml of 0.5% bupivacaine. Sedation requirements and pain levels were
      recorded. RESULTS: Ten biliary drainage procedures in 8 patients were performed
      for malignancy in 8 cases and for stones in 2. The mean midazolam use was 1.13 mg
      i.v., and the mean fentanyl requirement was 60.0 microg i.v. in the block
      patients. Two episodes of hypotension, which responded promptly to volume
      replacement, may have been related to the block. No serious complications were
      encountered. The mean pain score when traversing the chest wall, liver capsule,
      and upon entering the bile ducts was 0.1 on a scale of 0 to 10, with 1 patient
      reporting a pain level of 1 and 9 reporting 0. The mean peak pain score,
      encountered when manipulating at the common bile duct level or when addressing
      stones there, was 5.4 and ranged from 0 to 10. CONCLUSIONS: Thoracic
      paravertebral block with intravenous sedation supplementation appears to be a
      feasible method of pain control during biliary interventions.

PMID- 16988879
TI  - Aggravation of pre-existing atrioventricular block, Wenckebach type, provoked by
      application of X-ray contrast medium.
AB  - BACKGROUND: Significant bradycardia followed by cardiac arrest related to single
      bolus administration of X-ray contrast medium into a peripheral artery has not,
      to our knowledge, been described in the literature. METHODS AND RESULTS: While
      performing a percutaneous transluminal angioplasty of the left superficial
      femoral artery in a 68-year old patient with a pre-existing atrioventricular (AV)
      block, Wenckebach type, he developed an AV block III after a single bolus
      injection of intra-arterial X-ray contrast medium. CONCLUSION: We believe that
      application of contrast medium causes a transitory ischemia in the obstructed
      vessel and therefore elevation of endogenous adenosine. In the case of a
      previously damaged AV node this elevation of endogenous adenosine may be
      responsible for the development of a short period of third-degree AV block.

PMID- 16988881
TI  - EPR studies of recombinant horse L-chain apoferritin and its mutant (E
      53,56,57,60 Q) with haemin.
AB  - Structural similarities between ferritins and bacterioferritins have been
      extensively demonstrated. However, there is an essential difference between these
      two types of ferritins: whereas bacterioferritins bind haem, in-vivo, as Fe(II)
      protoporphyrin IX (this haem is located in a hydrophobic pocket along the 2-fold
      symmetry axes and is liganded by two axial Met 52 residues), eukaryotic ferritins
      are non-haem iron proteins. However, in in-vivo studies, a cofactor has been
      isolated from horse spleen apoferritin similar to protoporphyrin IX; in in-vitro
      experiments, it has been shown that horse spleen apoferritin is able to interact
      with haemin (Fe(III)-protoporphyrin IX). Studies of haemin incorporation into
      horse spleen apoferritin have been carried out, which show that the metal free
      porphyrin is found in a pocket similar to that which binds haem in
      bacterioferritins (Precigoux et al. 1994 Acta Cryst D50, 739-743). A mechanism of
      demetallation of haemin by L-chain apoferritins was subsequently proposed
      (Crichton et al. 1997 Biochem 36, 15049-15054) which involved four Glu residues
      (E 53,56,57,60) situated at the entrance of the hydrophobic pocket and appeared
      to be favoured by acidic conditions. To verify this mechanism, these four Glu
      have been mutated to Gln in recombinant horse L-chain apoferritin. We report here
      the EPR spectra of recombinant horse L-chain apoferritin and its mutant with
      haemin in basic and acidic conditions. These studies confirm the ability of
      recombinant L-chain apoferritin and its mutant to incorporate and demetallate the
      haemin in acidic and basic conditions.

PMID- 16988882
TI  - Significant EEG features involved in mathematical reasoning: evidence from
      wavelet analysis.
AB  - Using electroencephalographic (EEG) signals and a novel methodology based on
      wavelet measures in the time-scale domain, we evaluated cortex reactions during
      mathematical thinking. Our purpose was to extract more precise information from
      the cortex reactions during this cognitive task. Initially, the brain areas
      (lobes) of significant activation during the task are extracted using time
      averaged wavelet power spectrum estimation. Then, a refinement step makes use of
      statistical significance-based criteria for comparing wavelet power spectra
      between the task and the rest condition. EEG signals are recorded from 15 young
      normal volunteers using 30 scalp electrodes as participants performed one
      difficult arithmetic task and the results are compared with a rest situation. The
      results are in accordance with similar previous studies, showing activations of
      frontal and central regions. Compared with the alternative spectral-based
      techniques, the method we propose achieves higher task discrimination on the same
      dataset and provides additional detail-signal information to evaluate cortical
      reactivity during local cortical activation.

PMID- 16988883
TI  - Will filmed presentations of education and contact diminish mental illness
      stigma?
AB  - This study examines the impact of two versions of anti-stigma programs-education
      and contact-presented on videotape. A total of 244 people were randomly assigned
      to education or contact conditions and completed pre-test, post-test, and follow
      up measures of stereotypes. Results suggest that the education videotape had
      limited effects, mostly showing improvement in responsibility (people with mental
      illness are not to blame for their symptoms and disabilities). Watching the
      contact videotaped showed significant improvement in pity, empowerment, coercion,
      and segregation. Contact effects were evident at post-test and 1 week follow-up.
      Implications of these findings for future research are discussed.

PMID- 16988884
TI  - Bumblebees can be used in combination with juvenile hormone analogues and
      ecdysone agonists.
AB  - This study examined the lethal and sublethal effects on the beneficial insect
      Bombus terrestris by two classes of insect growth regulators (IGRs) that are
      commercially used in agriculture to control pest insects. Three juvenile hormones
      analogues (JHAs) (pyriproxyfen, fenoxycarb and kinoprene) and two ecdysone
      agonists or moulting accelerating compounds (MACs) (tebufenozide and
      methoxyfenozide) were tested. The bumblebee workers were exposed to the
      insecticides via three different routes of exposure: dermally by topical contact,
      and orally via the drinking sugar water or the pollen. In the first series of
      experiments the IGRs were applied at their respective maximum field recommended
      concentration (MFRC). These risk hazard tests showed that the tested IGRs caused
      no acute toxicity on the workers, and any compound had an adverse effect on
      reproduction (production of males). In addition, larval development was followed
      in the treated nests compared with the controls. After application of the two
      MACs and the JHA fenoxycarb no adverse effects were observed on larval
      development. However, in the nests where the workers were exposed to the JHAs
      pyriproxyfen and kinoprene higher numbers of dead larvae were scored. These
      larvae were third and fourth instars, implying a lethal blockage of development
      before metamorphosis. In a second test, a series of dilutions was made for
      kinoprene, and these results revealed that only the MFRC caused a toxic effect on
      the larval development. On the other hand, kinoprene at lower concentrations
      (0.0650 mg ai/l) had a stimulatory effect on brood production. It was remarkable
      that ovaries of such treated dominant workers were longer and contained more eggs
      than in the controls. In a last experiment, the cuticular uptake was determined
      for a JHA and MAC to evaluate to what extent worker bees accumulate these classes
      of IGRs. Cuticular uptake ranged from 34 to 83% at 24 h after topical
      application. Overall, the obtained results indicate that the tested IGRs at their
      recommended concentration are safe to be used in combination with B. terrestris.

PMID- 16988885
TI  - Genetic diversity and structure of an estuarine fish (Fundulus heteroclitus)
      indigenous to sites associated with a highly contaminated urban harbor.
AB  - Intense selection on isolated populations can cause loss of genetic diversity,
      which if persistent, reduces adaptive potential and increases extinction
      probability. Phenotypic evidence of inherited tolerance suggests that
      polychlorinated biphenyls (PCBs), have acted as strong selective agents on
      populations of a non-migratory fish, Fundulus heteroclitus, indigenous to heavily
      contaminated sites. To evaluate population genetic structure and test for effects
      of intense, multi-generational PCB contamination on genetic diversity, we used
      AFLP analysis on fish collected from six sites along the east coast of North
      America that varied widely in PCB contamination. The sites included a heavily
      contaminated urban harbor (New Bedford, MA), an adjacent moderately contaminated
      sub-estuary (Buzzards Bay, MA), and an uncontaminated estuary 60 km away
      (Narragansett, RI). AFLP markers distinguished populations at moderate and small
      scales, suggesting genetic differentiation at distances of 2 km or less. Genetic
      diversity did not differ across the study sites. Genome-wide diversity may have
      been preserved because of large effective population sizes and/or because the
      mechanism for genetic adaptation to these contaminants affected only a small
      number of loci. Alternatively, loss in diversity may have been restored with
      moderate levels of migration and relatively short generation time for this
      species.

PMID- 16988886
TI  - Physical health, self-reliance, and emotional control as moderators of the
      relationship between locus of control and mental health among men treated for
      prostate cancer.
AB  - This investigation examined the moderating effects of physical health and scripts
      for masculinity (i.e., self-reliance and emotional control) on the relationship
      between powerful other people locus of control and mental health for 230 men
      treated for prostate cancer. Regression analyses indicated that physical health
      and masculine gender scripts moderated the association between powerful other
      people locus of control and mental health. Specifically, men with poor physical
      health evinced negative mental health when they endorsed masculine gender scripts
      and believed powerful other people (i.e., family, friends, or peers) were
      influential in controlling their cancer. By comparison, men reporting poor
      physical health, strong beliefs that powerful other people controlled their
      cancer, and less adherence to masculine scripts experienced positive mental
      health. The authors discuss future research directions and potential mental
      health implications for men treated for prostate cancer.

PMID- 16988887
TI  - Type I interferons attenuate T cell activating functions of human mast cells by
      decreasing TNF-alpha production and OX40 ligand expression while increasing IL-10
      production.
AB  - Recent studies have demonstrated that mast cells not only mediate inflammatory
      reactions in type I allergy but also play an important role in adaptive immunity.
      In the present study, we investigated the effects of interferon-alpha, which
      shares the same receptor as IFN-beta, on human cord blood-derived mast cells.
      Mast cells produced TNF-alpha, and IL-10, and expressed OX40 ligand upon
      activation by crosslinking of FcepsilonRI. When treated with interferon-alpha,
      TNF-alpha production was decreased while IL-10 and TGF-beta productions were
      increased. Furthermore, flow cytometric analysis revealed that interferon-alpha
      downregulated expression OX40 ligand on mast cells which is crucial for mast cell
      T cell interaction. We confirmed that the viability of mast cells was not
      affected by interferon-alpha treatment. Accordingly, interferon-alpha-treated
      mast cells induced lower levels of CD4+ T cell proliferation compared with those
      without interferon-alpha treatment. These results suggest that type I interferons
      suppress T cell immune responses through their regulatory effects on mast cells.

PMID- 16988888
TI  - Effect of lisinopril on rat liver tissues in L-NAME induced hypertension model.
AB  - N(G)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) is a non-specific
      nitric oxide (NO) inhibitor and it has been used to eliminate the role of NO in
      many studies like animal models for hypertension. In this study, we aimed to
      investigate whether lisinopril treatment has any biochemical and/or
      histopathological effect on rat liver tissue in a L-NAME-induced hypertension
      model. Forty-eight 6-weeks-old male Spraque-Dawley rats were used in the study.
      The animals used in the study were randomly divided into four equal groups. To
      induce hypertension, L-NAME was added to drinking water at a concentration of 600
      mg/l and each rat was given 75 mg/kg/day of L-NAME for 6 weeks. Tail cuff
      systolic blood pressure (SBP) was measured at first, third, and sixth weeks.
      There was a significant difference between the experiment groups and controls. In
      only lisinopril given and L-NAME plus lisinopril administered groups, each rat
      was given 10 mg/kg of lisinopril for 6 weeks. At the end of the study, the
      animals were sacrificed. Blood and tissue samples were collected for biochemical
      and histopathological analysis. It has been observed that mean NO level was
      significantly decreased in L-NAME given group (p<0.05). Mean ALT levels were
      significantly increased in lisinopril and L-NAME plus lisinopril given groups,
      when compared with the control group (p<0.05). AST levels were in normal range in
      all groups (p>0.05). Hepatocyte degeneration was prominent in lisinopril given
      group, whereas mononuclear cell infiltration was significant in L-NAME given
      groups. Although the beneficial effects in L-NAME-induced hypertension treatment,
      lisinopril can lead to some unexpected results like hepatocyte degeneration,
      serum enzyme level elevation, and slight mononuclear cell infiltration.

PMID- 16988890
TI  - Cocrystal formation during cogrinding and storage is mediated by amorphous phase.
AB  - PURPOSE: The purpose of this work was to investigate the mechanisms of cocrystal
      formation during cogrinding and storage of solid reactants, and to establish the
      effects of water by cogrinding with hydrated form of reactants and varying RH
      conditions during storage. METHODS: The hydrogen bonded 1:1 carbamazepine
      saccharin cocrystal (CBZ-SAC) was used as a model compound. Cogrinding of solid
      reactants was studied under ambient and cryogenic conditions. The anhydrous, CBZ
      (III), and dihydrate forms of CBZ were studied. Coground samples were stored at
      room temperature at 0% and 75% RH. Samples were analyzed by XRPD, FTIR and DSC.
      RESULTS: Cocrystals prepared by cogrinding and during storage were similar to
      those prepared by solvent methods. The rate of cocrystallization was increased by
      cogrinding the hydrated form of CBZ and by increasing RH during storage.
      Cryogenic cogrinding led to higher levels of amorphization than room temperature
      cogrinding. The amorphous phase exhibited a T (g) around 41 degrees C and
      transformed to cocrystal during storage. CONCLUSIONS: Amorphous phases generated
      by pharmaceutical processes lead to cocrystal formation under conditions where
      there is increased molecular mobility and complementarity. Water, a potent
      plasticizer, enhances the rate of cocrystallization. This has powerful
      implications to control process induced transformations.

PMID- 16988891
TI  - An investigation of the validity and reliability of the Criminal Sentiments Scale
      in a sample of treated sex offenders.
AB  - The Criminal Sentiments Scale (CSS) purports to measure attitudes and values
      pertaining to and in support of criminal conduct (Andrews & Bonta, 2003). A
      sample of 72 sex offenders treated in a high intensity sex offender program
      completed the CSS pre- and post-treatment and was followed up for approximately 3
      years. The CSS demonstrated high internal consistency. Correlational and ROC
      analyses indicated that the CSS is a robust predictor of non-sexual violent and
      non-violent recidivism. The CSS also correlated significantly with the General
      Statistical Information on Recidivism Scale which assesses non-sexual recidivism
      risk. Similar analyses showed that the CSS did not predict sexual recidivism nor
      did it correlate with a tool that assesses sexual recidivism risk-the Static 99.
      The CSS scores changed significantly in the predicted direction following
      treatment. The present results suggest that the CSS is an internally consistent
      tool for the assessment of criminal sentiments among sex offenders and that it
      predicts non-sexual but not sexual recidivism.

PMID- 16988892
TI  - Religious affiliations among adult sexual offenders.
AB  - This article examines associations between self-reported religious affiliations
      and official offense histories among 111 incarcerated adult male sexual
      offenders. Four categories of religiosity were devised according to self-reported
      continuities and discontinuities in life-course religious affiliations: atheists,
      dropouts, converts, and stayers. ANCOVAs indicated that stayers (those who
      maintained religious involvement from childhood to adulthood) had more sexual
      offense convictions, more victims, and younger victims, than other groups.
      Results challenge assumptions that religious involvement should, as with other
      crime, serve to deter sexual offending behavior. Results are discussed in terms
      of social control and situational theories of crime.

PMID- 16988889
TI  - Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: role of
      sarcolemmal substrate transporters.
AB  - Cardiovascular disease is the primary cause of death in obesity and type-2
      diabetes mellitus (T2DM). Alterations in substrate metabolism are believed to be
      involved in the development of both cardiac dysfunction and insulin resistance in
      these conditions. Under physiological circumstances the heart utilizes
      predominantly long-chain fatty acids (LCFAs) (60-70%), with the remainder covered
      by carbohydrates, i.e., glucose (20%) and lactate (10%). The cellular uptake of
      both LCFA and glucose is regulated by the sarcolemmal amount of specific
      transport proteins, i.e., fatty acid translocase (FAT)/CD36 and GLUT4,
      respectively. These transport proteins are not only present at the sarcolemma,
      but also in intracellular storage compartments. Both an increased workload and
      the hormone insulin induce translocation of FAT/CD36 and GLUT4 to the sarcolemma.
      In this review, recent findings on the insulin and contraction signalling
      pathways involved in substrate uptake and utilization by cardiac myocytes under
      physiological conditions are discussed. New insights in alterations in substrate
      uptake and utilization during insulin resistance and its progression towards T2DM
      suggest a pivotal role for substrate transporters. During the development of
      obesity towards T2DM alterations in cardiac lipid homeostasis were found to
      precede alterations in glucose homeostasis. In the early stages of T2DM,
      relocation of FAT/CD36 to the sarcolemma is associated with the myocardial
      accumulation of triacylglycerols (TAGs) eventually leading to an impaired insulin
      stimulated GLUT4-translocation. These novel insights may result in new strategies
      for the prevention of development of cardiac dysfunction and insulin resistance
      in obesity and T2DM.

PMID- 16988893
TI  - The Oregon depo-Provera program: a five-year follow-up.
AB  - In 1999, the Oregon State Legislature, concerned about the risk certain sexual
      offenders might pose to their communities upon release from prison, enacted House
      Bill 2500. This bill required selected offenders to be evaluated prior to their
      release to determine whether medical treatment with medroxyprogesterone acetate
      (MPA), also known by its trade name of depo-Provera, was indicated to reduce
      their risk. The present study reviewed the first 275 men to be evaluated under
      this program from the years 2000 through 2004. Data were collected on diagnoses
      and outcome on three groups: men judged to need MPA who eventually went on to
      actually receive it; men recommended to receive MPA who, for a variety of
      reasons, did not receive the medication; and men deemed not to need MPA. Outcome
      measures included recidivism data, including reoffenses, parole violations, and
      reincarcerations, and whether these were sexual in nature. Data were also
      collected on employment and whether supervising officers believed the men in each
      group were doing well. Significant differences emerged among these three groups,
      with men actually receiving depo-Provera committing no new sexual offenses and
      also committing fewer overall offenses and violations compared to the other two
      groups. In addition, almost one third of men judged to need medication but who
      did not receive it committed a new offense and almost 60% of these were sexual in
      nature. While generalizations from these types of retrospective and partially
      subjective findings are inherently limited, the present study lends credence to
      the belief that, in selected offenders, anti-androgenic medication can be a
      valuable, if time-limited, addition to a cognitive and behavioral treatment
      program. Suggestions for more practical and far-reaching implementation of this
      adjunctive approach are offered.

PMID- 16988894
TI  - Bispectral index evaluation of the sedative effect of acupuncture in healthy
      volunteers.
AB  - OBJECTIVE: To evaluate the sedative effect of acupuncture in healthy volunteers
      by means of the BIS monitor. Secondary end-points were the evaluation of
      subjective sedative sensation induced by acupuncture and possible lasting of the
      sedative effect post needles removal. METHODS: We performed a cross-over, single
      blinded study on 10 healthy volunteers to evaluate objective and subjective
      sedative effect of acupuncture compared to sham acupuncture. We recorded heart
      rate, pulse-oxymetry, BIS at baseline, during a 20-min. stimulation period, and
      for the following 20 minutes after needles removal. Besides, we asked volunteers
      to score their subjective state by VAS at baseline, after the stimulation period
      (20th minute) and 20 minutes after needles removal. RESULTS: BIS values were not
      significantly different between true and sham acupuncture. A suggestive but not
      statistically significant difference was evident in VAS score, with true- better
      than sham acupuncture. There was no difference in the incidence of sleep during
      the experimental phases, nor in the incidence of insomnia or somnolence in the
      following 24 hours. HR and SpO2 remained always in a normal range. CONCLUSIONS:
      The sedative effect of true acupuncture was not different from that of sham
      acupuncture in healthy volunteers. We suggest that acupuncture could have a mild
      sedative action that can be demonstrated only treating anxious patients and not
      calm volunteers. In our opinion, the low potency of this technique can be an
      advantage allowing acupuncture safe application in a wide range of settings.

PMID- 16988895
TI  - Experimentation on humans and nonhumans.
AB  - In this article, I argue that it is wrong to conduct any experiment on a nonhuman
      which we would regard as immoral were it to be conducted on a human, because such
      experimentation violates the basic moral rights of sentient beings. After
      distinguishing the rights approach from the utilitarian approach, I delineate
      basic concepts. I then raise the classic "argument from marginal cases" against
      those who support experimentation on nonhumans but not on humans. After next
      replying to six important objections against that argument, I contend that moral
      agents are logically required to accord basic moral rights to every sentient
      being. I conclude by providing criteria for distinguishing ethical from unethical
      experimentation.

PMID- 16988896
TI  - Linear and nonlinear fetal heart rate analysis of normal and acidemic fetuses in
      the minutes preceding delivery.
AB  - Linear and nonlinear fetal heart rate (FHR) indices, namely mean FHR, interval
      index (II), very low, low and high frequencies, approximate (ApEn) and sample
      entropy (SampEn), were computed, immediately before delivery, in the initial and
      final FHR tracing segments, from 48 normal, 10 mildly acidemic and 10 moderate-to
      severely acidemic fetuses. Progression of labor was associated with a significant
      increase in linear frequency domain indices whereas nonlinear indices were
      significantly decreased. Moderate-to-severe fetal acidemia was associated with a
      significant decrease in nonlinear indices. The best discrimination between
      moderate-to-severe acidemic fetuses and the remaining cases was obtained
      combining II and ApEn(2,0.15), with a specificity of 71% and a sensitivity of
      80%. These findings support the hypothesis of increased autonomic nervous system
      activity in the final minutes of labor and of decreased central nervous system
      activity, both in the final minutes of labor and in moderate-to-severe acidemic
      fetuses.

PMID- 16988897
TI  - Artificial reproduction technologies (RTs) - all the way to the artificial womb?
AB  - In this paper, I argue that the development of an artificial womb is already well
      on its way. By putting together pieces of information arising from new scientific
      advances in different areas, (neo-natal care, gynecology, embryology, the human
      genome project and computer science), I delineate a distinctive picture, which
      clearly suggests that the artificial womb may become a reality sooner than we may
      think. Currently, there is a huge gap between the first stages of gestation
      (using in vitro fertilization) and the 22nd week (inside the womb). At the
      present time this gap seems an insurmountable barrier for fully developing a
      fetus outside a natural womb - a notion better known as ectogenesis. The history
      of science however, suggests that impenetrable barriers are such only
      temporarily. It is just a matter of time (and due research) until someone -
      intentionally or by chance - accesses the right answer and finds a way to
      overcome existing obstacles. Despite misgivings that the case of the artificial
      womb presents too many barriers, it would be naive to suppose things would happen
      any differently. I observe in this paper, that it is time to acknowledge the
      consequences of new developments in different areas of scientific research which
      are leading to the advent of an artificial womb; and I modestly suggest that we
      might initiate a discussion on this topic now, while we have still enough time to
      decide what we may want and why.

PMID- 16988898
TI  - Care as a mutual endeavour: experiences of a multiple sclerosis patient and her
      healthcare professionals.
AB  - In Dutch healthcare policy patients are seen as informed, autonomous experts and
      active decision makers with control over their illness and care. Healthcare
      professionals are expected to operate as providers of information. The purpose of
      this article is to argue that the consumerist approach of the patient
      professional relationship is not a productive way to envision the patient
      professional relationship. We argue that an interpretive/deliberative model is a
      more productive way to envision this relationship, especially in the care for
      people with a chronic illness. This is illustrated with a case study. It concerns
      a study of the experiences of a Multiple Sclerosis (MS) patient and healthcare
      professionals involved in her care. The presented stories show that the
      participants did not act in line with the roles and responsibilities embodied in
      the consumerism rhetoric in Dutch healthcare policy. Expectation of patients and
      healthcare professionals are better met when care is redefined as mutual
      endeavour in which the caring abilities of healthcare professionals and the
      vulnerability of chronically ill patients are taken into account.

PMID- 16988899
TI  - Two familial cases of high blood galactose of unknown aetiology.
AB  - We report two male siblings presenting as newborns with increased blood
      galactose, urinary excretion of galactitol, and normal galactose 1-phosphate on a
      breast milk diet. A lactose-free diet led to normalization of all metabolites,
      while reintroduction of galactose in the diet resulted in an accumulation of
      metabolites. Potential causes of galactosaemia include: (1) activities of three
      enzymes of galactose metabolism: galactokinase (GALK), galactose-1-phosphate
      uridyltransferase (GALT), and uridine diphosphate galactose 4'-epimerase (GALE),
      (2) portosystemic shunting, (3) Fanconi-Bickel syndrome, (4) tyrosinaemia. Each
      was excluded with appropriate tests. These two familial cases may represent a
      novel autosomal or X-linked recessive disorder of galactose metabolism, possibly
      due to a novel defect in the transport of galactose across the plasma membrane.

PMID- 16988901
TI  - Abstracts of the 2nd European Conference on Tumor Angiogenesis and Antiangiogenic
      Therapy (ECTA), 14-16 September 2006, Munich, Germany.

PMID- 16988900
TI  - Large neutral amino acids in the treatment of phenylketonuria (PKU).
AB  - Large neutral amino acids (LNAAs) have been used on a limited number of patients
      with phenylketonuria (PKU) with the purpose of decreasing the influx of
      phenylalanine (Phe) to the brain. In earlier studies on mice with PKU
      (ENU(2)/ENU(2)), LNAAs were given and a surprising decline in blood Phe
      concentrations was observed. The formula used in the mouse experiment (PreKUnil)
      lacked lysine. Therefore, a new formulation of LNAAs (NeoPhe) was developed,
      introducing changes in the concentration of some amino acids and adding lysine,
      so that such a mixture could be used in humans. The new formula was found to be
      effective in reducing blood Phe concentration in mice by about 50% of the
      elevated levels. Patients with PKU were given LNAAs and blood Phe concentrations
      were determined in an open-label study. Three centers--in Russia, the Ukraine and
      the USA--took part in the study. NeoPhe was given at 0.5 g/kg per day in three
      divided doses to eight subjects with PKU and at 1.0 g/kg per day to three
      patients, for one week. The NeoPhe resulted in decrease of elevated blood Phe by
      50% in both groups. The preliminary data from this study are encouraging and a
      double blind placebo-controlled trial will be required to show long-term efficacy
      and tolerance of LNAAs in the treatment of PKU.

PMID- 16988902
TI  - The minimal, phase-transition model for the cell-number maintenance by the
      hyperplasia-extended homeorhesis.
AB  - Oncogenic hyperplasia is the first and inevitable stage of formation of a (solid)
      tumor. This stage is also the core of many other proliferative diseases. The
      present work proposes the first minimal model that combines homeorhesis with
      oncogenic hyperplasia where the latter is regarded as a genotoxically activated
      homeorhetic dysfunction. This dysfunction is specified as the transitions of the
      fluid of cells from a fluid, homeorhetic state to a solid, hyperplastic-tumor
      state, and back. The key part of the model is a nonlinear reaction-diffusion
      equation (RDE) where the biochemical-reaction rate is generalized to the one in
      the well-known Schlogl physical theory of the non-equilibrium phase transitions.
      A rigorous analysis of the stability and qualitative aspects of the model, where
      possible, are presented in detail. This is related to the spatially homogeneous
      case, i.e. when the above RDE is reduced to a nonlinear ordinary differential
      equation. The mentioned genotoxic activation is treated as a prevention of the
      quiescent G0-stage of the cell cycle implemented with the threshold mechanism
      that employs the critical concentration of the cellular fluid and the
      nonquiescent-cell-duplication time. The continuous tumor morphogeny is described
      by a time-space-dependent cellular-fluid concentration. There are no sharp
      boundaries (i.e. no concentration jumps exist) between the domains of the
      homeorhesis- and tumor-cell populations. No presumption on the shape of a tumor
      is used. To estimate a tumor in specific quantities, the model provides the time
      dependent tumor locus, volume, and boundary that also points out the tumor shape
      and size. The above features are indispensable in the quantitative development of
      antiproliferative drugs or therapies and strategies to prevent oncogenic
      hyperplasia in cancer and other proliferative diseases. The work proposes an
      analytical-numerical method for solving the aforementioned RDE. A few topics for
      future research are suggested.

PMID- 16988903
TI  - Serial Endosymbiotic Theory (set): the biosemiotic update.
AB  - The Serial Endosymbiotic Theory explains the origin of nucleated eukaryotic cells
      by a merging of archaebacterial and eubacterial cells. The paradigmatic change is
      that the driving force behind evolution is not ramification but merging. Lynn
      Margulis describes the symbiogenetic processes in the language of mechanistic
      biology in such terms as "merging", "fusion", and "incorporation". Biosemiotics
      argues that all cell-cell interactions are (rule-governed) sign-mediated
      interactions, i.e., communication processes. As the description of plant
      communication demonstrates, the biosemiotic approach is not limited to the level
      of molecular biology, but is also helpful in examining all sign-mediated
      interactions between organisms on the phenotypic level. If biosemiotics also uses
      the notions of "language" and "communication" to describe non-human sign-mediated
      interactions, then the underlying scientific justification of such usage should
      be critically considered. Therefore, I summarize the history of this discussion
      held between 1920 and 1980 and present its result, the pragmatic turn.

PMID- 16988904
TI  - Biodiversity in the age of ecological indicators.
AB  - The multifarious nature of biodiversity is considered in relation to difficulties
      of definite determination and managerial mandates for monitoring. At a micro
      scale there is some convergence with the concept of community, but the linkage is
      largely lost in the spectra of temporal scope, spatial scales, successional
      seres, and taxonomic trajectories. Practicality points to selecting suitable
      suites of indicators as surrogates for particular purposes. Domains of partial
      ordering on multiple indicators constitute comparable collectives, whereas
      different domains require recognition of special situations. Theoretical treatise
      and practical process can proceed in parallel, with dialogue and cross
      fertilization serving to invigorate and inspire; whereas compulsive concern for
      completeness and consistency can be counter-productive as well as unduly
      expensive. Inability to completely capture all aspects of biodiversity in one
      full formulation is interesting and integral to issues of biocomplexity.

PMID- 16988905
TI  - With a machete through the jungle: some thoughts on community diversity.
AB  - This short communication includes comments on a single sentence cited from a
      recent paper by C. Ricotta. I discuss shortly the relationship between diversity
      and classification as well as the possibility of expressing diversity for
      continuous variables. A simple example shows that the notion of diversity can be
      expanded to situations without an underlying classification. I suggest an
      evenness formula based on absolute deviations from the perfectly even
      distribution. If expressed for species data and multiplied by number of species
      in the community, this becomes an easily interpretable diversity measure. It is
      stressed that conventional diversity formulae cannot be informative on community
      structure, but there is a solution.

PMID- 16988906
TI  - Ecological diversity and biodiversity as concepts for conservation planning:
      comments on Ricotta.
AB  - Ricotta argues against the existence of a unique measure of biodiversity by
      pointing out that no known measure of alpha-diversity satisfies all the adequacy
      conditions that have traditionally been set for it. While that technical claim is
      correct, it is not relevant in the context of defining biodiversity which is most
      usefully measured by beta-diversity. The concept of complementarity provides a
      closely related family of measures of biodiversity which can be used for
      systematic conservation planning. Moreover, these measures cannot be replaced by
      summary statistics but must rely on inventories of biodiversity surrogates at
      candidate sites for conservation.

PMID- 16988908
TI  - The time-profile of the PBMC HSP70 response to in vitro heat shock appears
      temperature-dependent.
AB  - Heat shock proteins (HSPs) are synthesised by cells subsequent to a stress
      exposure and are known to confer protection to the cell in response to a second
      challenge. HSP induction and decay are correlated to thermotolerance and may
      therefore be used as a biomarker of thermal history. The current study tested the
      temperature-dependent nature of the heat shock response and characterised its
      time profile of induction. Whole blood from 6 healthy males (Age: 26 +/- (SD) 2
      yrs; Body mass 74.2 +/- 3.8 kgs; VO(2max): 49.1 +/- 4.0 ml.kg(-1).min(-1)) were
      isolated and exposed to in vitro heat shock (HS) at 37, 38, 39, 40, and 41
      degrees C for a period of 90 min. After HS the temperature was returned to 37
      degrees C and intracellular HSP70 was quantified from the leukocytes at 0, 2, 4,
      and 6 h after heat treatment. The concentration of HSP70 was not different
      between temperatures (P > 0.05), but the time-profile of HSP70 synthesis appeared
      temperature-dependent. At control (37 degrees C) and lower temperatures (38-39
      degrees C) the mean HSP70 concentration increased up to 4 h post HS (P < 0.05)
      and then returned towards baseline values by 6 h post HS. With in vitro
      hyperthermic conditions (40-41 degrees C), the time-profile was characterised by
      a sharp rise in HSP70 levels immediately after treatment (P < 0.05 for 40 degrees
      C at 0 h), followed by a progressive decline over time. The results suggest a
      temperature-dependent time-profile of HSP70 synthesis. In addition, the
      temperature at which HSP70 is inducted might be lower than 37 degrees C.

PMID- 16988909
TI  - Effects of resistance training and protein plus amino acid supplementation on
      muscle anabolism, mass, and strength.
AB  - This study examined 10 wks of resistance training and the ingestion of
      supplemental protein and amino acids on muscle performance and markers of muscle
      anabolism. Nineteen untrained males were randomly assigned to supplement groups
      containing either 20 g protein (14 g whey and casein protein, 6 g free amino
      acids) or 20 g dextrose placebo ingested 1 h before and after exercise for a
      total of 40 g/d. Participants exercised 4 times/wk using 3 sets of 6-8
      repetitions at 85-90% of the one repetition maximum. Data were analyzed with two
      way ANOVA (p < 0.05). The protein supplement resulted in greater increases in
      total body mass, fat-free mass, thigh mass, muscle strength, serum IGF-1, IGF-1
      mRNA, MHC I and IIa expression, and myofibrillar protein. Ten-wks of resistance
      training with 20 g protein and amino acids ingested 1 h before and after exercise
      is more effective than carbohydrate placebo in up-regulating markers of muscle
      protein synthesis and anabolism along with subsequent improvements in muscle
      performance.

PMID- 16988910
TI  - Selective determination of mimosine and its dihydroxypyridinyl derivative in
      plant systems.
AB  - Our observations on the growth stimulatory nature of mimosine, (beta-(3-hydroxy-4
      pyridon-1-yl)-L-alanine), the toxic non-protein plant amino acid, in some model
      experimental systems, warranted sensitive and selective routine estimations. For
      the determination of both mimosine and DHP, an indirect spectrophotometric method
      was developed based on their individual reaction with known excess of DZSAM and
      by estimating the remaining DZSAM with N-(1-naphthyl)ethylene-diamine (NEDA). The
      resultant decrease in the secondary coupled product was measured at 540 nm. On
      equimolar basis, DHP had 40% of the reactivity of mimosine while interference
      from other relevant compounds was 15-35%. The determination of mimosine and DHP
      in tissue samples under different physiological conditions was effected after
      paper chromatographic separation of mimosine and DHP with distinctly differing
      Rf, from other compounds. The indirect method is superior in terms of absolute
      selectivity, sensitivity and ease of applicability with linear decreases in
      absorbance, proportional to increasing concentrations of mimosine from 0.1 to
      0.75 microM or DHP from 0.2 to 1.5 microM and with recoveries of 99.2 to 100.5%.

PMID- 16988912
TI  - Actein and a fraction of black cohosh potentiate antiproliferative effects of
      chemotherapy agents on human breast cancer cells.
AB  - The purpose of this study was to determine whether the triterpene glycosides
      present in black cohosh enhance the growth inhibitory effects of specific breast
      cancer chemotherapy agents. Black cohosh roots and rhizomes were extracted with
      methanol (MeOH)/water (H (2)O) and fractionated by solvent-solvent partitioning
      to yield three fractions: hexane, ethyl acetate (EtOAc) and water. The EtOAc
      fraction is enriched in triterpene glycosides, including the compound actein.
      Actein and the EtOAc fraction were then tested, alone and in combination with
      chemotherapy agents, for growth inhibition of the ER (-) Her2 overexpressing
      breast cancer cell line MDA-MB-453. We found that actein exerted a synergistic
      effect on growth inhibition when combined with doxorubicin or 5-flourouracil.
      Synergy was also obtained when the EtOAc fraction was combined with doxorubicin.
      Actein increased the percent of cells in the G1 phase of the cell cycle and had a
      similar effect when combined with 5-flourouracil or doxorubucin. Actein enhanced
      the induction of apoptosis by paclitaxel, 5-flourouracil or doxorubicin. Our
      results indicate that relatively low concentrations of actein or the EtOAc
      fraction of black cohosh can cause synergistic inhibition of human breast cancer
      cell proliferation when combined with different classes of chemotherapy agents.

PMID- 16988913
TI  - The pinealocytes of the human pineal gland: A light and electron microscopic
      study.
AB  - The pinealocytes of the pineal gland of children and adults were studied at both
      light and electron microscopic levels. The pinealocytes were classified into
      light and dark pinealocytes on the basis of their shape, nuclear infolding,
      cytoplasmic contents and staining density. The light pinealocytes outnumber the
      dark pinealocytes and both of them have thin processes. The light pinealocytes
      have round or oval cell bodies and nuclei and have vesicles and ribbons. The dark
      pinealocytes showed more variations in their shape. The nuclear membrane of the
      dark cells showed numerous infoldings with deep invagination of parts of the
      cytoplasm within the nuclear folds, giving the appearance of nuclear pellets. The
      dark pinealocytes contain pigment in their cytoplasm. In addition to the light
      and dark pinealocytes a very small cell type with an extremely thin and elongated
      cell body and nucleus was found. The cells of this type were almost always
      associated with vacuoles filled with flocculent material and accumulations of
      presumptive secretion in the extracellular compartment. The findings of this
      study were discussed in the light of the published data about the pinealocytes of
      human and non-human species.

PMID- 16988914
TI  - The effects of an electromagnetic field on the boundary tissue of the
      seminiferous tubules of the rat: A light and transmission electron microscope
      study.
AB  - Human beings are unavoidably exposed to ambient electromagnetic fields (EMF)
      generated from various electrical devices and from power transmission lines.
      Controversy exists about the effects of EMF on various organs. One of the
      critical issues is that EMF may adversely affect the reproductive system. In
      order to examine this 30 rat pups were exposed to 50 Hz EMF (non-ionising
      radiation) during in utero development (approximately 3 weeks) and postnatal life
      (5 weeks). Groups of exposed rats were subsequently left in an environment free
      of EMF in order to observe recovery, if any, from the changes induced by EMF on
      the boundary tissue of the seminiferous tubules. The materials were processed and
      observed under a light and a transmission electron microscope. In the
      experimental rats boundary tissue was found disrupted at various layers. This
      tissue showed infoldings, which were perhaps due to the loss of collagen and
      reticular fibrils from the inner and outer non-cellular layers. The outer non
      cellular layer, which was thinner than that of the control, was stripped away
      from the myoid cell layer in multiple regions, giving a "blister-like"
      appearance. The myoid cells showed fewer polyribosomes, pinocytotic vesicles and
      glycogen granules. Most mitochondria were found to lack cristae. The connections
      between individual myoid cells were apparently lost. There were signs of recovery
      in the boundary tissue following withdrawal from EMF exposure. These results
      suggest that EMF exposure may cause profound changes in the boundary tissue of
      the seminiferous tubules. Therefore exposure to EMF may result in pathological
      changes that lead to subfertility and infertility.

PMID- 16988915
TI  - The anatomy of the tympanic sinus.
AB  - The tympanic sinus is one of the most important structures of the human temporal
      bone. Located in its vicinity are the round window, posterior semicircular canal
      and facial nerve. The study was performed on 30 temporal bones taken from adult
      cadavers of both sexes. After the tympanic sinus had been identified, its
      morphological features were evaluated. The sinus was then measured using a
      graticule with an accuracy of 0.05 mm. Also measured were the shortest distances
      from the tympanic sinus to the neighbouring structures (the lateral and posterior
      semicircular canal, the facial nerve canal and the jugular fossa). The
      measurements were performed under a surgical microscope with eye-piece graduation
      of 0.05 mm accuracy. Four main morphological types of fossa of the tympanic sinus
      and two main developmental forms, a deep sinus and a shallow sinus, were
      distinguished. The existence of a deep sinus was associated with absence of the
      bridge and the sinus was shallower when the bridge was prominent. The very deep
      sinuses were located close to the facial canal, in some cases penetrating deep in
      its vicinity (in some cases even going beyond two thirds of the canal's
      circumference), which poses a real risk of facial nerve damage during surgical
      removal of a lesion located in close proximity to the nerve. In most cases the
      tympanic sinus is elliptical in shape and its long diameter lies in the vertical
      plane (mean value: 2.73 x 2.23 mm). The mean distances from the tympanic sinus to
      the facial nerve canal, lateral semicircular canal, posterior semicircular canal
      and jugular fossa were 1.5 mm, 2.1 mm, 1.59 mm and 5.5 mm respectively. No
      correlation was observed between the measurement results and either sex or side.

PMID- 16988916
TI  - The morphology of the right atrioventricular valve in the adult human heart.
AB  - Studies of the morphometry and normal anatomy of the tricuspid valve are in
      constant demand. Knowledge of the morphology of the normal tricuspid valve may be
      useful, for example in the context of the transfer of a leaflet of the tricuspid
      valve for repair or insufficiency of the mitral valve, in repair of the tricuspid
      valve after blunt chest trauma and in other surgical techniques of this region.
      In this study, performed in a group of 107 formalin-fixed adult human hearts, we
      attempted to assess the form and number of the main and accessory cusps in the
      tricuspid valve. Rare anatomical variants of the tricuspid valve were found.
      Using a planimeter we evaluated the surface area of the tricuspid valve and
      particular leaflets. With the help of a Vernier scale we measured the length and
      height of individual leaflets of the tricuspid valve and the length of the
      commissures. No differences were found between the length of the anterior and
      septal leaflets. The posterior leaflet was the shortest, while the anterior
      leaflet was the widest and had the largest surface area. The posterior leaflet
      was wider than the septal leaflet and had the smallest surface area. No
      differences were found between the main and accessory leaflets in the length of
      the commissures.

PMID- 16988917
TI  - An anatomical study of the origins of the medial circumflex femoral artery in the
      Turkish population.
AB  - The medial circumflex femoral artery (MCFA) usually branches from the deep
      femoral artery (DFA). It may also branch from the femoral artery (FA). In this
      study 100 inguinal regions of 50 cadavers were investigated. In 79 extremities
      (79%) MCFA branched from DFA, while in 15 (15%) it branched from FA. In four
      extremities (4%) MCFA was found to be double; in each case one of MCFAs branched
      from FA and the other from DFA. In one of these four cases the lateral circumflex
      femoral artery (LCFA) was also double. In one case we found a common trunk of DFA
      and MCFA and in another case a common trunk of MCFA, DFA and LCFA. Clinicians
      must be familiar with the variations of this clinically important artery to
      improve their success in the diagnosis and treatment of pathologies in the
      region.

PMID- 16988918
TI  - Vanilloid receptor type 1-immunoreactive nerves in the rat urinary bladder and
      primary afferent neurones: The effects of age.
AB  - The vanilloid receptor (VR1) is a molecular integrator of various painful
      stimuli, including capsaicin, acid and high temperature. VR1 protein functions
      both as a receptor for capsaicin and a transducer of noxious thermal stimuli. In
      addition, VR1 is well characterised at the terminals of sensory nerves involved
      in the pain pathway. VR1 is also expressed in a capsaicin-sensitive and peptide
      containing sub-population of primary sensory nerves. Indirect
      immunohistochemistry was used to examine the distribution of nerves
      immunoreactive (ir) for VR1 in the base of the urinary bladder and in the
      neurones of the lumbosacral dorsal root ganglia (L1-L2 and L6-S1) of young adult
      (3 months) and aged (24 months) male rats. Semi-quantitative estimations of nerve
      densities were assessed and quantitative studies were also used to examine the
      effects of age on the percentage of VR1-ir dorsal root ganglion neurones. The
      bladder base in young adults showed dense VR1-ir fibres within the urothelium and
      in the subepithelium and fibres ranging from sparse to moderate in number in the
      muscle coat. In comparison to the young animals, the aged rats showed sparse to
      moderate densities of VR1-ir nerves in the subepithelium and sparse fibres in the
      muscle layers. In the lumbosacral dorsal root ganglia the percentage of VR1-ir
      neuronal profiles showed a significant reduction from (mean +/- SEM) 17.8 +/- 2%
      in the young adult to 12 +/- 1.6 in the aged rats. The present findings suggest
      that the effects of VR1 on bladder function (nociception and reflex micturition)
      are influenced by age and the reduction with age of VR1-ir neurones in the dorsal
      root ganglia could also have important implications for the micturition reflex.

PMID- 16988919
TI  - Impairment of the oral stereognosis in the partial anterior open bite.
AB  - The study was performed in 20 children with partial anterior open bite and in 20
      children of a control group. Stereognosis was evaluated on the basis of correct
      recognition responses to silicone pieces of the different shapes. Pieces were put
      on the dorsal surface of the tongue close to its apex. It was evident that the
      stereognostic ability was impaired in children with anterior open bite. This
      ability also decreased after infiltration anaesthesia of the tongue. The study
      indicated that the tongue plays an important role in oral stereognosis.

PMID- 16988920
TI  - The morphology and function of the quadrate ligament.
AB  - There is a paucity of information in the literature regarding the quadrate
      ligament and the information that does exist is extremely conflicting. We
      dissected 30 cadavers (60 sides) to determine the morphology and function of this
      enigmatic ligament. A quadrate ligament (thickening of the elbow joint capsule)
      was found in all specimens. In all specimens this band was distinct from the
      circumferential fibres of the annular ligament. The length, width, and thickness
      of the quadrate ligament were found to be 11 mm, 8 mm, and 1 mm respectively.
      This ligament not only aided in securing the neck of the radius to the ulna but
      also resisted excessive supination and, to a lesser degree, pronation of the
      forearm. Following transection of the quadrate ligament, the head of the radius
      was secured to the ulna considerably less firmly and supination and pronation
      increased by 10 to 20 degrees and 5 to 8 degrees respectively. The quadrate
      ligament contributes to proximal radioulnar stability, limits the "spin" of this
      joint, and should be considered in manipulation, surgery, or imaging of the
      proximal forearm.

PMID- 16988921
TI  - Absence of the musculocutaneous nerve together with unusual innervation of the
      median nerve.
AB  - During routine anatomical dissections, absence of the musculocutaneous nerve was
      determined in a 58-year-old male cadaver. Moreover, the biceps brachii and
      brachialis muscles were innervated by two separate branches which divided from
      the median nerve instead of the musculocutaneous nerve. From a branch that
      divides from the main trunk of the median nerve at nearly the middle of the arm a
      motor branch again divided that innervated the brachialis muscle and a sensory
      branch that conveyed the sense of the lateral part of the forearm. Furthermore,
      it was found that the brachial artery divided into its terminal branches, the
      radial and ulnar arteries. We believe that this rare variation of the median
      nerve will shed light upon surgical procedures involving the median nerve.

PMID- 16988922
TI  - A case of atypical insertion of the levator scapulae.
AB  - Anatomical variations in the musculature of the spine have the potential to cause
      functional and postural abnormalities, which in turn could lead to chronic
      myofascial and skeletal pain. We present a unilateral case of a 71-year-old
      Caucasian female in which the left levator scapulae muscle gave rise to an
      accessory head that inserted, by way of a flat aponeurotic band, to the
      ligamentum nuchae, the tendon of the rhomboideus major and the superior aspect of
      the serratus posterior superior muscle. The innervation was provided by a branch
      of the dorsal scapular nerve. By exerting unilateral traction on the vertebrae
      and surrounding musculature, this unusual variation might have resulted in
      clinical consequences including scoliosis and movement abnormalities of the head
      and neck as well as myofascial pain syndrome.

PMID- 16988923
TI  - A retrotracheal right subclavian artery in association with a vertebral artery
      and thyroidea ima.
AB  - The retro-oesophageal right subclavian artery is an anatomical abnormality
      encountered by anatomists and pathologists and, more recently, interventional
      cardiologists and thoracic surgeons with an incidence of 0.2-2% in the
      population. We report a case of a retrotracheal right subclavian artery which
      originated distally along the left aortic arch and coursed between the trachea
      and the oesophagus. Additionally, the aortic arch gave rise to a common trunk,
      which subsequently bifurcated to yield to a right vertebral artery and a left
      thyroidea ima, replacing the left inferior thyroid artery. Consequently the right
      and the left recurrent laryngeal nerves were found to recur normally. The
      possible embryonic development of these branching patterns and their clinical
      significance is discussed.

PMID- 16988924
TI  - The ossified interclinoid ligament.
AB  - The paper presents an anatomical description of the ossified interclinoid
      ligament which was found in a male human skull. In the case studied the ossified
      ligament exists as a bony bridge between the anterior and posterior clinoid
      processes on the left side of the skull. The length of this connection was
      measured as 5.0 mm, while its thickness was 3.2 mm. We conjecture that the
      presence of a considerably thick bony trabecula within the sella region might
      have had an impact on the course of the internal carotid artery or the oculomotor
      nerve, causing compression of these structures.

PMID- 16988927
TI  - Influence of glyphosate on Rhizoctonia and Fusarium root rot in sugar beet.
AB  - This study tests the effect of glyphosate application on disease severity in
      glyphosate-resistant sugar beet, and examines whether the increase in disease is
      fungal or plant mediated. In greenhouse studies of glyphosate-resistant sugar
      beet, increased disease severity was observed following glyphosate application
      and inoculation with certain isolates of Rhizoctonia solani Kuhn and Fusarium
      oxysporum Schlecht. f. sp. betae Snyd. & Hans. Significant increases in disease
      severity were noted for R. solani AG-2-2 isolate R-9 and moderately virulent F.
      oxysporum isolate FOB13 on both cultivars tested, regardless of the duration
      between glyphosate application and pathogen challenge, but not with highly
      virulent F. oxysporum isolate F-19 or an isolate of R. solani AG-4. The increase
      in disease does not appear to be fungal mediated, since in vitro studies showed
      no positive impact of glyphosate on fungal growth or overwintering structure
      production or germination for either pathogen. Studies of glyphosate impact on
      sugar beet physiology showed that shikimic acid accumulation is tissue specific
      and the rate of accumulation is greatly reduced in resistant cultivars when
      compared with a susceptible cultivar. The results indicate that precautions need
      to be taken when certain soil-borne diseases are present if weed management for
      sugar beet is to include post-emergence glyphosate treatments.

PMID- 16988928
TI  - Automatic internal calibration in liquid chromatography/Fourier transform ion
      cyclotron resonance mass spectrometry of protein digests.
AB  - Accurately measured peptide masses can be used for large-scale protein
      identification from bacterial whole-cell digests as an alternative to tandem mass
      spectrometry (MS/MS) provided mass measurement errors of a few parts-per-million
      (ppm) are obtained. Fourier transform ion cyclotron resonance (FTICR) mass
      spectrometry (MS) routinely achieves such mass accuracy either with internal
      calibration or by regulating the charge in the analyzer cell. We have developed a
      novel and automated method for internal calibration of liquid chromatography
      (LC)/FTICR data from whole-cell digests using peptides in the sample identified
      by concurrent MS/MS together with ambient polydimethylcyclosiloxanes as internal
      calibrants in the mass spectra. The method reduced mass measurement error from
      4.3 +/- 3.7 ppm to 0.3 +/- 2.3 ppm in an E. coli LC/FTICR dataset of 1000 MS and
      MS/MS spectra and is applicable to all analyses of complex protein digests by
      FTICRMS.

PMID- 16988929
TI  - Benzyl ions from 1,1-(2,2'-dimethoxyphenyl)-substituted 2-methylpropanes under
      electron ionization.
AB  - The electron ionization (EI)-induced fragmentations of a series of 1,1-(2,2'
      dimethoxyphenyl)-substituted 2-methylpropanes (1-20) in both 70 eV and mass
      analyzed ion kinetic energy (MIKE) spectra have been investigated. The EI-MS
      spectra of these compounds are characterized by the presence of abundant benzyl
      ions. These ions result from competitive hydrogen migration from the 2- and 2'
      methoxy groups on the carbenium center of the diphenylmethyl cations formed by
      benzylic cleavage of the molecular ions. The relative abundances of the benzyl
      ions arising from such competitive processes are discussed and rationalized. The
      steric effect of the 3- or 3'-substituents is the main discriminating factor
      between the two competitive processes. The structural information, arising either
      from the 70 eV or the MIKE spectra, is discussed.

PMID- 16988930
TI  - Monitoring minimal residual disease and controlling drug resistance in chronic
      myeloid leukaemia patients in treatment with imatinib as a guide to clinical
      management.
AB  - Imatinib mesylate, binding to the inactive conformation of Bcr-Abl tyrosine
      kinase and suppressing the Ph chromosome positive clone, has revolutionized the
      treatment of chronic myeloid leukaemia (CML) patients. Given the high rates of
      clinical and cytogenetic remission achieved, the molecular monitoring of BCR-ABL
      transcript levels by RT-qPCR has become always more important to assess minimal
      residual disease. Recently, recommendations for harmonizing current methodologies
      for detecting and measuring BCR-ABL transcripts in CML patients have been
      suggested. Studies of imatinib-treated patients have determined that the BCR-ABL
      levels measured early in therapy may predict durable cytogenetic remission and in
      turn prolonged progression free-survival or acquisition of resistance. The major
      mechanism of imatinib resistance is clonal expansion of leukaemia cells with
      mutations in the Bcr-Abl fusion tyrosine kinase. The early reduction of such
      mutations may allow timely treatment intervention to prevent or overcome
      resistance. We review current trends in the management of chronic myeloid
      leukaemia patients undergoing treatment with tyrosine kinase inhibitors.

PMID- 16988931
TI  - Mutational analysis of the HER2 gene in lung tumors from Caucasian patients:
      mutations are mainly present in adenocarcinomas with bronchioloalveolar features.
AB  - Activating mutations in the tyrosine kinase domain of the HER2 gene have recently
      been reported in lung adenocarcinomas, mainly in East Asian patients. Our study
      was devised to evaluate the prevalence and nature of HER2 mutations in lung
      adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene
      was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation
      polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2
      mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame
      duplications/insertions at codons 776-779 (YVMA), the other 2 were base
      substitutions resulting in aminoacid changes. The hotspot mutation at bases 776
      779 was previously found to be the most frequent HER2 mutation in Asiatic
      patients. The distribution of mutations was significantly different between
      conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with
      bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of
      290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations
      was slightly higher in females (4.1%) than in males (1.8%) and in never smokers
      (3.1%) than in smokers (1.9%), but differences were not statistically
      significant. This series of tumors was also investigated for EGFR and K-ras
      mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations
      in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually
      exclusive events. The presence of HER2 mutations in a subset of patients with
      lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase
      inhibitors.

PMID- 16988932
TI  - Physicians are different when they learn communication skills: influence of the
      locus of control.
AB  - PURPOSE: Although it is widely recognised that educational interventions may be
      more effective for people with an 'internal' Locus of Control (who believe that
      life outcomes are controlled by their own characteristics or actions) compared to
      people with an 'external' Locus of Control (who believe that life outcomes are
      controlled by external forces such as luck, fate or others), no study has yet
      assessed the influence of physicians' Locus of Control (LOC) on communication
      skills learning. This study aims to test the hypothesis that, in a communication
      skills training program, physicians with an 'internal' LOC would demonstrate
      communication skills acquisition to a greater degree than those with an
      'external' LOC. METHODS: A non-randomised longitudinal intervention study was
      conducted between January 1999 and April 2001. Sixty-seven volunteer physicians
      from private and institutional practice in Belgium participated in a learner
      centred, skills-focused, practice-oriented communication skills training program.
      Communication skills changes were assessed in 2 standardised simulated interviews
      before and after training (one two-person and one three-person interview).
      Communication skills were assessed using the Cancer Research Campaign Workshop
      Evaluation Manual. Physicians' LOC was assessed using the Rotter I-E scale.
      Communication skills changes of the upper and lower third of physicians in
      respect of their scores on this scale were compared using group by time repeated
      measures of variance. RESULTS: In the two-person and three-person interviews,
      changes in the use of open directive questions were more important among
      physicians with an "internal" LOC compared with changes observed among physicians
      with an 'external' LOC (P=0.066 and P=0.004, respectively). In the three-person
      interview, changes in the use of directive questions, assessing functions and
      moderate feelings stated explicitly were more important among physicians with an
      'internal' LOC compared with changes observed among physicians with an 'external'
      LOC (P= 0.001; P=0.002 and P=0.011 respectively). CONCLUSION: This study shows
      that physicians' LOC is a psychological characteristic that could influence the
      efficacy of a communication skills training program. This evidence supports the
      idea that a psychological characteristic such as 'internal' LOC may facilitate
      communication skills acquisition through physicians' belief that communication
      with patients may be controlled by physicians themselves.

PMID- 16988935
TI  - Abstracts of the The Movement Disorder Society's 10th International Congress of
      Parkinson's Disease and Movement Disorders, October 30-November 2, 2006, Kyoto,
      Japan.

PMID- 16988933
TI  - Comparative structural analysis of a novel glutathioneS-transferase (ATU5508)
      from Agrobacterium tumefaciens at 2.0 A resolution.
AB  - Glutathione S-transferases (GSTs) comprise a diverse superfamily of enzymes found
      in organisms from all kingdoms of life. GSTs are involved in diverse processes,
      notably small-molecule biosynthesis or detoxification, and are frequently also
      used in protein engineering studies or as biotechnology tools. Here, we report
      the high-resolution X-ray structure of Atu5508 from the pathogenic soil bacterium
      Agrobacterium tumefaciens (atGST1). Through use of comparative sequence and
      structural analysis of the GST superfamily, we identified local sequence and
      structural signatures, which allowed us to distinguish between different GST
      classes. This approach enables GST classification based on structure, without
      requiring additional biochemical or immunological data. Consequently, analysis of
      the atGST1 crystal structure suggests a new GST class, distinct from previously
      characterized GSTs, which would make it an attractive target for further
      biochemical studies.

PMID- 16988938
TI  - Attenuation of disease phenotype through alternative translation initiation in
      low-penetrance retinoblastoma.
AB  - Hereditary predisposition to retinoblastoma (RB) is caused by germline mutations
      in the retinoblastoma 1 (RB1) gene and transmits as an autosomal dominant trait.
      In the majority of cases disease develops in greater than 90% of carriers.
      However, reduced penetrance with a large portion of disease-free carrier is seen
      in some families. Unambiguous identification of the predisposing mutation in
      these families is important for accurate risk prediction in relatives and their
      genetic counseling but also provides conceptual information regarding the
      relationship between the RB1 genotype and the disease phenotype. In this study we
      report a novel mutation detected in 10 individuals of an extended family, only
      three of whom are affected by RB disease. The mutation comprises a 23-basepair
      (bp) duplication in the first exon of RB1 (c.43_65dup) producing a frameshift in
      exon 1 and premature chain termination in exon 2. Mutations resulting in
      premature chain termination classically are associated with high penetrance
      disease, as message translation may not generate functional product and nonsense
      mediated RNA decay (NMD) frequently eliminates the mutant transcript. However,
      appreciable NMD does not follow from the mutation described here and transcript
      expression in tissue culture cells and translation in vitro reveals that
      alternative in-frame translation start sites involving Met113 and possibly Met233
      are used to generate truncated RB1 products (pRB94 and pRB80), known and
      suspected to exhibit tumor suppressor activity. These results strongly suggest
      that modulation of disease penetrance in this family is achieved by internal
      translation initiation. Our observations provide the first example for rescue of
      a chain-terminating mutation in RB1 through alternative translation initiation.

PMID- 16988939
TI  - Preliminary open trial of interpersonal counseling for subsyndromal depression
      following miscarriage.
AB  - Miscarriage occurs in 10-20% of clinically recognized pregnancies and is
      associated with two- to fourfold increases in depressive symptoms. No counseling
      programs for depressed miscarrying women have been manualized or evaluated for
      safety and efficacy. We investigated whether depressive symptoms decline
      substantially among miscarrying women receiving one to six weekly sessions of
      manualized, telephone-administered interpersonal counseling (IPC), a variant of
      interpersonal psychotherapy (IPT) in an open trial. Depressive symptom levels
      were measured with the Center for Epidemiologic Studies-Depression (CES-D) scale.
      Of 65 women evaluated, 24 were study eligible; 17 consented to participate.
      Change in symptom levels was evaluated by comparing baseline to postintervention
      CES-D scores in an intention to treat (ITT) sample (n=17) and a completer
      subsample (n=9). The latter sample comprised women reevaluated postintervention.
      In the ITT sample, the CES-D mean score declined from 25.4 to 18.8 [mean within
      subject change=6.6, 95% confidence interval (CI)=1.4-11.6]; in the completer
      subsample, it declined from 23.6 to 11.2 (mean within-subject change=12.3, 95%
      CI=4.0-20.7). Findings from this small open trial suggest that IPC decreases
      depressive symptoms after miscarriage. A randomized, controlled trial of IPC's
      safety and efficacy with depressed miscarrying women is warranted.

PMID- 16988940
TI  - Protein kinase B modulates the sensitivity of human neuroblastoma cells to
      insulin-like growth factor receptor inhibition.
AB  - The potential of the novel insulin-like growth factor receptor (IGF-IR) inhibitor
      NVP-AEW541 as an antiproliferative agent in human neuroblastoma was investigated.
      Proliferation of a panel of neuroblastoma cell lines was inhibited by NVP-AEW541
      with IC(50) values ranging from 0.15 to 5 microM. Experiments using an IGF-IR
      neutralizing antibody confirmed that the IGF-IR was essential to support growth
      of neuroblastoma cell lines. The expression levels of the IGF-IR in individual
      neuroblastoma cell lines did not correlate with the sensitivities to NVP-AEW541,
      while coexpression of the IGF-IR and the insulin receptor (IR) correlated with
      lower sensitivity to the inhibitor in some cell lines. Intriguingly, high levels
      of activation of Akt/protein kinase B (PKB) and phosphorylation of the ribosomal
      S6 protein were observed in neuroblastoma cell lines with decreased sensitivities
      to NVP-AEW541. Inhibition of Akt/PKB activity restored the sensitivity of
      neuroblastoma cells to the IGF-IR inhibitor. Transfection of neuroblastoma cells
      with activated Akt or ribosomal protein S6 kinase (S6K) decreased the sensitivity
      of the cells to NVP-AEW541. IGF-I-stimulated proliferation of neuroblastoma cell
      lines was completely blocked by NVP-AEW541, or by a combination of an inhibitor
      of phosphoinositide 3-kinase and rapamycin. In addition to its antiproliferative
      effects, NVP-AEW541 sensitized neuroblastoma cells to cisplatin-induced
      apoptosis. Together, our data demonstrate that NVP-AEW541 in combination with
      Akt/PKB inhibitors or chemotherapeutic agents may represent a novel approach to
      target human neuroblastoma cell proliferation.

PMID- 16988941
TI  - CYP2A13 expressed in human bladder metabolically activates 4-aminobiphenyl.
AB  - Cigarette smoking is the predominant risk factor for bladder cancer. Aromatic
      amines such as 4-aminobiphenyl (ABP) is the major carcinogens found in tobacco
      smoke. Although it is generally accepted that ABP is metabolically activated via
      N-hydroxylation by CYP1A2 in human liver, previous studies using Cyp1a2-null mice
      indicated the involvement of other enzyme(s). Here we found that CYP2A13 can
      metabolically activate ABP to show genotoxicity by Umu assay. The K(m) and V(max)
      values for ABP N-hydroxylation by recombinant CYP2A13 in E. coli were 38.5 +/-
      0.6 microM and 7.8 +/- 0.0 pmol/min/pmol CYP, respectively. The K(m) and V(max)
      values by recombinant CYP1A2 were 9.9 +/- 0.9 microM and 39.6 +/- 0.9
      pmol/min/pmol CYP, respectively, showing 20-fold higher intrinsic clearance than
      CYP2A13. In human bladder, CYP2A13 mRNA, but not CYP1A2, is expressed at a
      relatively high level. Human bladder microsomes showed ABP N-hydroxylase activity
      (K(m) = 34.9 +/- 4.7 microM and V(max) = 57.5 +/- 1.9 pmol/min/mg protein),
      although the intrinsic clearance was 5-fold lower than that in human liver
      microsomes (K(m) = 33.2 +/- 2.0 microM and V(max) = 293.9 +/- 5.8 pmol/min/mg
      protein). The activity in human bladder microsomes was prominently inhibited by 8
      methoxypsoralen, but not by fluvoxamine, anti-CYP1A2 or anti-CYP2A6 antibodies.
      CYP2S1, which is expressed in human bladder and has relatively high amino acid
      identities with CYP2As, did not show detectable ABP N-hydroxylase activity. In
      conclusion, although the enzyme responsible for ABP N-hydroxylation in human
      bladder microsomes could not be determined, we found that CYP2A13 metabolically
      activates ABP.

PMID- 16988942
TI  - Flat penile lesions: the infectious "invisible" link in the transmission of human
      papillomavirus.
AB  - Although it has been widely accepted that high-risk human papillomavirus (hrHPV)
      is sexually transmitted, limited insight is available about the clinical
      manifestations of hrHPV infection in men and their contribution in the viral
      spread. Here, we reviewed the literature on the relationship between hrHPV and
      the presence of penile lesions. Flat penile lesions have similar predilection
      sites as HPV, often contain hrHPV as identified by DNA in situ hybridization in
      biopsy specimens, show a high association with hrHPV as identified by PCR in
      penile scrapes of lesional sites and are associated with high viral copy numbers.
      Absence of flat lesions is generally associated with very low HPV copy numbers or
      absence of HPV. Therefore, we argue that these lesions form the reservoir of
      hrHPV in men and contribute to the viral spread. Their bare visibility with the
      naked eye and their high degree of spontaneous healing explain why flat penile
      lesions have slipped the attention of the clinician. Combining an HPV DNA test
      with a visual inspection after acetic acid application offers a more reliable
      interpretation of a positive HPV test in men, as it helps to distinguish
      positivity that is very likely to reflect a productive HPV infection from
      potentially HPV infections with very low copy numbers or HPV contamination by the
      sex partner. Future trials of HPV vaccines in men should take into account not
      only the presence of penile HPV but also the presence of flat penile lesions as
      an outcome measure for the efficacy of a vaccine.

PMID- 16988943
TI  - MC1R common variants, CDKN2A and their association with melanoma and breast
      cancer risk.
AB  - We sought to examine the association between MC1R variants and the risk of
      melanoma and breast cancer in Polish population. We also determined the
      prevalence of compound heterozygous carriers of MC1R and CDKN2A (A148T) variants.
      We examined 500 unselected melanoma cases, 511 consecutive invasive breast cancer
      patients, 800 newborns, 421 healthy adults matched for sex and age with the
      melanoma cases and 511 healthy women matched for sex and age with the breast
      cancer cases. A statistically significant association of all 4 MC1R variants with
      the melanoma risk was found. For the R151C variant p value was 0.000008 and odds
      ratio 2.9; for the V60L variant p value was 0.007 and OR 1.78; for the R160C p
      was 0.006 and OR 1.76; for the R163Q p was 0.015 and odds ratio 2.1. None of the
      compound heterozygotes were significantly over-represented among any of the
      melanoma cases, the highest OR (4.2) observed in patients harbouring the A148T
      variant in CDKN2A and the R151C variant in MC1R. Positive association was found
      between carrying any of the MC1R variants and (i) increased occurrence of
      melanoma among I degree relatives of the carriers; (ii) increased occurrence of
      melanoma on UV-non-exposed skin areas. We also observed a tendency of increased
      risk of multiple melanomas among carriers of MC1R variants. The haplotype
      analysis demonstrates that MC1R variants do not co-occur in cis, compound
      carriers have both alleles affected. We found no association with the MC1R
      variants and breast cancer risk. In conclusion, the results of this population
      based study show herein that MC1R variants are associated with increased melanoma
      risk in the Polish population. The risk of disease seems to be increased
      additively for patients harbouring also the CDKN2A common variant A148T.

PMID- 16988944
TI  - Downregulation of the KIP family members p27(KIP1) and p57(KIP2) by SKP2 and the
      role of methylation in p57(KIP2) inactivation in nonsmall cell lung cancer.
AB  - Knowing the status of molecules involved in cell cycle control in cancer is vital
      for therapeutic approaches aiming at their restoration. The p27(KIP1) and
      p57(KIP2) cyclin-dependent kinase inhibitors are nodal factors controlling normal
      cell cycle. Their expression in normal lung raises the question whether they have
      a mutual exclusive or redundant role in nonsmall cell lung cancer (NSCLC). A
      comparative comprehensive analysis was performed in a series of 70 NSCLCs. The
      majority of cases showed significantly reduced expression of both members
      compared to normal counterparts. Low KIP protein levels correlated with increased
      proliferation, which seems to be histological subtype preponderant. At
      mechanistic level, degradation by SKP2 was demonstrated, in vivo and in vitro, by
      siRNA-methodology, to be the most important downregulating mechanism of both KIPs
      in NSCLC. Decreased p57(KIP) (2)-transcription complements the above procedure in
      lowering p57(KIP2)-protein levels. Methylation was the main cause of decreased
      p57(KIP) (2)-mRNA levels. Allelic loss and imprinting from LIT1 mRNA contribute
      also to decreased p57(KIP2) transcription. In vitro recapitulation of the in vivo
      findings, in A549 lung cells (INK4A-B((-/-))), suggested that inhibition of the
      SKP2-degradation mechanism restores p27(KIP1) and p57(KIP2) expression. Double
      siRNA treatments demonstrated that each KIP is independently capable of
      restraining cell growth. An additional demethylation step is required for
      complete reconstitution of p57(KIP2) expression in NSCLC.

PMID- 16988945
TI  - Impact of IGF-1R/EGFR cross-talks on hepatoma cell sensitivity to gefitinib.
AB  - Epidermal growth factor receptor (EGFR)- and type 1 insulin-like growth factor
      receptor (IGF-1R)-dependent pathways are up-regulated in hepatocellular carcinoma
      (HCC), and cross-talks between both pathways have been described in other
      systems. Gefitinib, a specific EGFR inhibitor, has shown to reduce significantly,
      although not completely, HCC formation in rat cirrhotic liver. Here, we
      investigated whether IGF-1R-dependent pathways may interfere with EGFR signalling
      in hepatoma cells and, if so, whether such cross-talks may affect the antitumoral
      effect of gefitinib in these cells. We show that the proliferative action of IGF2
      in HepG2 and Hep3B cells requires EGFR activation through the autocrine/paracrine
      release of amphiregulin. Thus, IGF2-induced extracellular signal-regulated kinase
      activity and DNA synthesis were inhibited by neutralizing antibodies against
      either EGFR or amphiregulin and by TAPI-1, a pharmalogical inhibitor of tumor
      necrosis factor-alpha converting enzyme, a sheddase of amphiregulin. Accordingly,
      IGF2 and EGF stimulating effects on cell proliferation were both strongly
      repressed by gefitinib. However, while gefitinib blocked Akt activation by EGF,
      it had no effect on Akt activation by IGF2 and did not cause apoptosis by its
      own. AG1024, a selective IGF-1R inhibitor, induced apoptosis and this effect was
      potentiated by gefitinib. In conclusion, we show that in HCC cells IGF2/IGF-1R
      activation triggers proliferative and survival signals through EGFR-dependent and
      -independent mechanisms, respectively. The IGF2/IGF-1R survival pathway may
      contribute to gefitinib resistance in these cells. Therefore, the inhibition of
      IGF2/IGF-1R signalling could potentiate the anti-tumoral effect of gefinitib in
      HCC.

PMID- 16988946
TI  - Expression of activated platelet-derived growth factor receptor in stromal cells
      of human colon carcinomas is associated with metastatic potential.
AB  - Platelet-derived growth factor receptor (PDGF-R) expression has been reported in
      a variety of cancers, including colorectal, breast, lung, ovarian and pancreatic
      cancers, but the role of PDGF-R expression in the development and progression of
      colon carcinoma has not yet been elucidated. The purpose of this study was to
      examine the expression of PDGF and PDGF-R in human colon carcinomas. The
      expression of PDGF, PDGF-R and phosphorylated PDGF-R (p-PDGF-R) was examined by
      immunofluorescence in 12 surgical specimens of colon carcinoma and in human colon
      carcinoma cells growing in the subcutis (ectopic site) and the cecal wall
      (orthotopic site) of nude mice. In most surgical specimens, tumor cells expressed
      PDGF-A and -B subunits, without corresponding levels of PDGF-Ralpha and PDGF
      Rbeta. PDGF-Rbeta was predominantly expressed by tumor-associated stromal cells
      and pericytes of tumor vasculature. The expression of PDGF-Rbeta in the stroma
      was associated with advanced stage disease. Under culture conditions, human colon
      carcinoma cell lines expressed PDGF-A and -B, but not PDGF-R. In orthotopic
      tumors, the KM12 cells (Duke's stage B) expressed PDGF-A and -B, but PDGF-Rbeta
      was expressed only by stromal cells and pericytes in the tumor vasculature. This
      expression of PDGF-Rbeta by stromal cells and pericytes was higher in tumors
      growing at the orthotopic site than in those at the ectopic site. The expression
      of PDGF-Rbeta in the stroma was higher in highly metastatic KM12SM tumors than in
      low metastatic KM12C tumors. In conclusion, the expression of PDGF-Rbeta in
      stromal cells is influenced by the organ-specific microenvironment and is
      associated with metastatic potential.

PMID- 16988947
TI  - Mechanism of apoptosis with the involvement of calpain and caspase cascades in
      human malignant neuroblastoma SH-SY5Y cells exposed to flavonoids.
AB  - Neuroblastoma is the most common extracranial solid tumor in children causing
      death at pre-school age, as no cure has yet been developed. We investigated the
      proteolytic mechanisms for apoptosis in human malignant (N-type) neuroblastoma SH
      SY5Y cells following exposure to flavonoids such as apigenin (APG), (-)
      epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG) and genistein
      (GST). We found decrease in viability of SH-SY5Y cells with an increase in dose
      of APG, EGC, EGCG and GST. Predominantly apoptosis occurred following exposure of
      SH-SY5Y cells to 50 microM APG, 50 microM EGC, 50 microM EGCG and 100 microM GST
      for 24 hr. Apoptosis was associated with increases in intracellular free [Ca(2+)]
      and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of
      caspase-9, calpain and caspase-3. Induction of apoptosis with APG and GST showed
      activation of caspase-12 as well. Activation of caspase-3 could cleave the
      inhibitor-of-caspase-activated DNase (ICAD) to release and translocate caspase-3
      activated DNase (CAD) to the nucleus. Activation of caspase-8 cleaved Bid to
      truncated Bid (tBid) in cells treated with EGC and EGCG. EGC and EGCG induced
      apoptosis with caspase-8 activation and mitochondria-mediated pathway, whereas
      APG and GST caused apoptosis via an increase in intracellular free [Ca(2+)] with
      calpain activation and mitochondria-mediated pathway. Activation of different
      proteases for cell death was confirmed using caspase-8 inhibitor II, calpeptin
      (calpain inhibitor), caspase-9 inhibitor I and caspase-3 inhibitor IV. Thus,
      plant-derived flavonoids cause cell death with activation of proteolytic
      activities of calpain and caspases in SH-SY5Y cells, and therefore serve as
      potential therapeutic agents for controlling the growth of neuroblastoma.

PMID- 16988948
TI  - 'What does it mean?' Uncertainty, trust and communication following treatment for
      pre-cancerous cervical abnormalities.
AB  - The early detection of pre-cancerous cervical conditions has risen dramatically,
      prompting more in-depth investigations regarding psychological implications
      inherent within the diagnosis and treatment of this condition. This study aimed
      to identify factors that influence women's experience of diagnosis and treatment
      of cervical abnormalities and factors that facilitate positive adjustment. Using
      a semi-structured telephone interview, we interviewed 21 women (age 24-54)
      treated at a colposcopy clinic. Systematic recruitment of women with varying
      degrees of cervical abnormality (CIN 1-3) and time since treatment was undertaken
      to ensure representation of all relevant experiences and allow the identification
      of long-term factors. Coding of audio-taped, transcribed interviews and searching
      for themes was achieved by using NUD*IST software. The results identified
      uncertainty, trust and communication as the key factors for women following
      diagnosis and treatment. The primary concern following diagnosis was related to
      cancer but changed to a more prominent concern with future reproductive issues in
      the post-treatment period. The majority of women acknowledged the importance of
      the doctor's empathic communication style. These findings have important
      implications for future studies and clinical practice.

PMID- 16988949
TI  - Validation of the Retardation Rating Scale for detecting depression in geriatric
      inpatients.
AB  - OBJECTIVES: Validation in the elderly of the Retardation Rating Scale (RRS),
      which includes items related to motor and mental retardation but not vegetative
      items, and may be particularly well-suited for the diagnosis of depression in the
      elderly. METHODS: One hundred and sixty-five geriatric inpatients (105
      depressed), aged 65 and over, without dementia, neuroleptic medication and
      increased risk of slowed mobility, were assessed with the RRS and three validated
      'gold-standard' scales for geriatric depression (Hamilton Depression Rating
      Scale, Montgomery and Asberg Depression Rating Scale, Geriatric Depression
      Scale). Factor analysis used varimax rotation, Cronbach's, Spearman's and
      Ferguson's coefficients and the Mann-Whitney U-test to evaluate construct and
      internal consistency. Convergent validity and Receiver Operating Characteristics
      curves were also analyzed. RESULTS: Factor analysis retained three interpretable
      domains: (1) motor items (45% of the variance); (2) mental items and (3) the
      cognitive items. Internal consistency was high (alpha = 0.91). Each item was
      strongly correlated with the total RRS score and associated with depression. The
      RRS showed good convergent validity and its total score increased with depression
      severity. A cut-off score of 10 yielded 79% sensitivity and 80% specificity, with
      80% of the patients properly classified, that is 15% more than standard observer
      scales. CONCLUSION: RRS is a valid screening tool for depression and improves
      recognition of depression in geriatric inpatients.

PMID- 16988950
TI  - Old age mental health services in England: implementing the National Service
      Framework for Older People.
AB  - BACKGROUND: There is much variation in the services provided for older people
      with mental health problems. In England, the National Service Framework for Older
      People (NSFOP) sought to address these inconsistencies and improve care. This
      study describes the situation three years after its publication. METHODS: A
      postal survey of old age psychiatrists collected data on the NSFOP mental health
      model: the range of specialist mental health provision, the nature of the
      specialist:generic service interface and the degree of
      interdisciplinary/interagency working. RESULTS: Three hundred and eighteen (72%)
      consultants responded. Considerable differences existed in the deployment of key
      professionals within community teams, with more than a third lacking ring-fenced
      social work time. Few services had dedicated rehabilitation beds and nearly a
      third lacked separate facilities for people with organic and functional
      illnesses. Increasing numbers of consultants had access to a memory clinic and
      there was some suggestion that liaison services were developing, but little
      indication of increased support for care homes. Several services had yet to agree
      protocols with primary care, or to implement measures promoting effective
      information-sharing and integrated care, and there was little evidence that the
      introduction of the Single Assessment Process (SAP) had significantly changed
      practice. Although just over half of consultants reported that mental health
      services were improving, less than a quarter considered community provision
      adequate. CONCLUSIONS: Three years after the publication of the NSFOP there
      remained significant gaps in services for older people with mental health
      problems and substantial variation in provision between districts.

PMID- 16988951
TI  - Multifaceted psychosocial intervention program for breast cancer patients after
      first recurrence: feasibility study.
AB  - We developed a novel multifaceted psychosocial intervention program which
      involves screening for psychological distress and comprehensive support including
      individually tailored psychotherapy and pharmacotherapy provided by mental health
      professionals. The purpose of the present study was to investigate the
      feasibility of the intervention program and its preliminary usefulness for
      reducing clinical psychological distress experienced by patients with recurrent
      breast cancer. The subjects who participated in the 3 months intervention program
      completed psychiatric diagnostic interview and several self-reported measures
      regarding psychological distress, traumatic stress, and quality of life. The
      assessments were conducted before the intervention (T1), after the intervention
      (T2), and 3 months after the intervention (T3). A total of 50 patients
      participated in the study. The rates of participation in and adherence to the
      intervention program were 85 and 86%, respectively. While the proportion of
      psychiatric disorders at T2 (11.6%) was not significantly different from that at
      T1 (22.0%) (p = 0.15), the proportion of that at T3 (7.7%) had significantly
      decreased compared with that at T1 (p = 0.005). The novel intervention program is
      feasible, is a promising strategy for reducing clinically manifested
      psychological distress and further controlled studies are warranted.

PMID- 16988953
TI  - Treatment of cellulite with optical devices: an overview with practical
      considerations.
AB  - Cellulite is a common condition in women for which treatment is frequently
      requested. Its etiology is unknown, but a myriad of factors including genetics,
      hormones, and inflammation appear to contribute to its formation. Despite the
      popularity of therapies touting their effectiveness for this pervasive condition,
      few have proven long-lasting benefits. Lasers and light sources are the latest
      devices to have entered the cellulite therapeutic market. This paper describes
      these optical devices and provides an overview of their published effectiveness.

PMID- 16988954
TI  - Structural dynamics of the mitochondrial ADP/ATP carrier revealed by molecular
      dynamics simulation studies.
AB  - The mitochondrial adenosine diphosphate/adenosine triphosphate (ADP/ATP) carrier
      has been recently crystallized in complex with its specific inhibitor
      carboxyatractyloside (CATR). In the crystal structure, the six-transmembrane
      helix bundle that defines the nucleotide translocation pathway is closed on the
      matrix side due to sharp kinks in the odd-numbered helices. The closed
      conformation is further sealed by the loops protruding into the matrix that
      interact through an intricate network of charge-pairs. To gain insight into its
      structural dynamics we performed molecular dynamics (MD) simulation studies of
      the ADP/ATP carrier with and without its cocrystallized inhibitor. The two
      trajectories sampled a conformational space around two different configurations
      characterized by distinct salt-bridge networks with a significant shift from
      inter- to intrarepeat bonding on the matrix side in the absence of CATR. Analysis
      of the geometrical parameters defining the transmembrane helices showed that even
      numbered helices can undergo a face rotation, whereas odd-numbered helices can
      undergo a change in the wobble angle with a conserved proline acting as molecular
      hinge. Our results provide new information on the dynamical properties of the
      ADP/ATP carrier and for the first time yield a detailed picture of a stable
      carrier conformation in absence of the inhibitor.

PMID- 16988955
TI  - Kinetic and structural properties of inorganic pyrophosphatase from the
      pathogenic bacterium Helicobacter pylori.
AB  - Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate (PPi)
      to orthophosphate (Pi) and controls the level of PPi in cells. PPase plays an
      essential role in energy conservation and provides the energy for many
      biosynthetic pathways. The Helicobacter pylori pyrophosphatase (HpPPase) gene was
      cloned, expressed, purified, and found to have a molecular weight of 20 kDa. The
      K(m) and V (max) of HpPPase were determined as 214.4 microM and 594 micromol Pi
      min(-1) mg(-1), respectively. PPi binds Mg(2+) to form a true substrate that
      activates the enzyme. However, free PPi could be a potent inhibitor for HpPPase.
      The effects of the inhibitors NaF, ATP, iminodiphosphate, and N-ethylmaleimide on
      HpPPase activity were evaluated. NaF showed the highest inhibition of the enzyme.
      Crystal structures of HpPPase and the PPi-HpPPase complex were determined.
      HpPPase comprises three alpha-helices and nine beta-strands and folds as a barrel
      structure. HpPPase forms a hexamer in both the solution and crystal states, and
      each monomer has its own PPi-binding site. The PPi binding does not cause a
      significant conformational change in the PPi-HpPPase complex, which might
      represent an inhibition state for HpPPase in the absence of a divalent metal ion.

PMID- 16988956
TI  - Critical assessment of the automated AutoDock as a new docking tool for virtual
      screening.
AB  - A major problem in virtual screening concerns the accuracy of the binding free
      energy between a target protein and a putative ligand. Here we report an example
      supporting the outperformance of the AutoDock scoring function in virtual
      screening in comparison to the other popular docking programs. The original
      AutoDock program is in itself inefficient to be used in virtual screening because
      the grids of interaction energy have to be calculated for each putative ligand in
      chemical database. However, the automation of the AutoDock program with the
      potential grids defined in common for all putative ligands leads to more than
      twofold increase in the speed of virtual database screening. The utility of the
      automated AutoDock in virtual screening is further demonstrated by identifying
      the actual inhibitors of various target enzymes in chemical databases with
      accuracy higher than the other docking tools including DOCK and FlexX. These
      results exemplify the usefulness of the automated AutoDock as a new promising
      tool in structure-based virtual screening.

PMID- 16988957
TI  - Depressive symptoms among older adults in urban and rural areas.
AB  - OBJECTIVES: To determine if there are differences in depressive symptoms between
      residents of urban areas, small town zones, and predominantly rural regions and
      to determine factors associated with depressive symptoms among these groups of
      residents. METHOD: The study was set in the Canadian province of Manitoba amongst
      a community-dwelling population of older adults who were cognitively intact. The
      design of the study was a cross-sectional survey and measures included age,
      gender, education, living arrangements, number of persons providing
      companionship, perceived adequacy of income, functional impairment, self-rated
      health and the Center for Epidemiologic Studies-Depression (CES-D) scale.
      Urban/rural residence was measured by grouping Census sub-divisions according to
      1991 Census population: urban (>19,999); small town (2500 to 19,999); or
      predominantly rural (<2500). RESULTS: In the total sample (n = 1382), 11.5%
      exhibited depressive symptoms: 11.6% in urban areas (n = 844); 14.0% in small
      town zones (n = 250); 9.0% in predominantly rural regions (n = 288) (p > 0.05,
      chi-square test). No rural-urban differences were seen in multivariate models. In
      predominantly rural regions, living alone, perceiving one's income as inadequate,
      and having functional impairment were associated with depressive symptoms. The
      only significant factor in small town zones was poorer self-rated health whereas
      in urban areas, poorer self-rated health, functional impairment, and fewer
      persons providing companionship were significantly related to depressive
      symptoms. CONCLUSIONS: We did not observe rural-urban differences. However, the
      factors associated with depressive symptoms varied among older adults living in
      predominantly rural regions, in small towns, and in urban areas.

PMID- 16988958
TI  - Coupled atomic charge selectivity for optimal ligand-charge distributions at
      protein binding sites.
AB  - Charge optimization as a tool for both analyzing and enhancing binding
      electrostatics has become an attractive approach over the past few years. An
      interesting feature of this method for molecular design is that it provides not
      only the optimal charge magnitudes, but also the selectivity of a particular
      atomic center for its optimal charge. The current approach to compute the charge
      selectivity at a given atomic center of a ligand in a particular binding process
      is based on the binding-energy cost incurred upon the perturbation of the optimal
      charge distribution by a unit charge at the given atomic center, while keeping
      the other atomic partial charges at their optimal values. A limitation of this
      method is that it does not take into account the possible concerted changes in
      the other atomic charges that may incur a lower energetic cost than perturbing a
      single charge. Here, we describe a novel approach for characterizing charge
      selectivity in a concerted manner, taking into account the coupling between the
      ligand charge centers in the binding process. We apply this novel charge
      selectivity measure to the celecoxib molecule, a nonsteroidal anti-inflammatory
      agent binding to cyclooxygenase 2 (COX2), which has been recently shown to also
      exhibit cross-reactivity toward carbonic anhydrase II (CAII), to which it binds
      with nanomolar affinity. The uncoupled and coupled charge selectivity profiles
      over the atomic centers of the celecoxib ligand, binding independently to COX2
      and CAII, are analyzed comparatively and rationalized with respect to available
      experimental data. Very different charge selectivity profiles are obtained for
      the uncoupled versus coupled selectivity calculations.

PMID- 16988959
TI  - Comparison of germanium oxide fibers with silica and sapphire fiber tips for
      transmission of erbium: YAG laser radiation.
AB  - BACKGROUND AND OBJECTIVES: Endoscopic applications of the Erbium:YAG laser have
      been limited due to the lack of a suitable optical fiber delivery system. The
      purpose of this study was to compare the transmission of Er:YAG laser radiation
      through germanium oxide trunk fibers with silica and sapphire fiber tips for
      potential use in contact tissue ablation during endoscopy. STUDY DESIGN/MATERIALS
      AND METHODS: Er:YAG laser radiation with a wavelength of 2.94 microm, pulse
      length of 300 microseconds, pulse energies from 5 to 1,360 mJ, coupled into pulse
      repetition rates of 3-10 Hz, was through 1-m-long germanium oxide fibers with
      either 1-cm-long, 550-microm-diameter silica or sapphire tips. RESULTS:
      Transmission through the germanium oxide/sapphire fibers measured 65+/-5%
      compared with 55+/-4% for the germanium oxide/silica fibers (P<0.05). The damage
      threshold for the hybrid fibers averaged 309+/- 44 mJ and 126+/-43 mJ,
      respectively (n = 7 fibers each) (P<0.05). The highest pulse energies transmitted
      through the fibers were 700 mJ and 220 mJ, respectively. CONCLUSIONS: Improved
      index-matching of the trunk fiber and fiber tip at 2.94 microm resulted in higher
      transmission and damage thresholds for the germanium oxide/sapphire fibers. The
      germanium oxide/sapphire fiber may represent a promising mid-infrared optical
      fiber delivery system for use in endoscopic applications of the Er:YAG laser
      requiring a flexible, biocompatible, and robust fiber delivery system for contact
      tissue ablation.

PMID- 16988960
TI  - The relative stress scale, a useful instrument to identify various aspects of
      carer burden in dementia?
AB  - OBJECTIVE: To identify carer and patient characteristics associated with various
      aspects of burden of care. METHOD: The burden on 196 carers, each caring for one
      patient with dementia, was rated by means of the Relative Stress Scale (RSS).
      Patients were assessed with the Mini Mental State Examination (MMSE), the
      Disability Assessment for Dementia (DAD) and the Neuropsychiatric Inventory
      (NPI). RESULTS: Factor analysis of the RSS resulted in three subgroups:
      'emotional distress', 'social distress' and 'negative feelings'. The total NPI
      score contributed to the explanation of the RSS total score and the three RSS
      subgroup scores with an explanatory power of 37% for total RSS, 34% for emotional
      distress, 27% for social distress and 20% for negative feelings. In multiple
      regression analysis, total NPI, DAD%, the carer being a wife and the hours spent
      caring per week, contributed to the explanation of total RSS with an explanatory
      power of 48%. Total NPI, the carer being a female and the hours spent caring,
      explained 38% of the variance in 'emotional distress'. Total NPI, the DAD%-score,
      contact with the patient on a daily basis and the hours spent caring, explained
      'social distress' (49%). 'Negative feelings' were associated with total NPI,
      younger patients and the carer being a wife (27%). CONCLUSIONS: The RSS offers an
      opportunity to differentiate between different patterns of distress. This
      facilitates the creation of tailored intervention to reduce the strain of caring.

PMID- 16988970
TI  - Effects of local infusion of OP-1 on particle-induced and NSAID-induced
      inhibition of bone ingrowth in vivo.
AB  - Excessive polyethylene wear particles from joint replacements may lead to
      periprosthetic osteolysis and loosening. Nonsteroidal anti-inflammatory drugs
      (NSAIDs) decrease fracture healing and bone ingrowth. We hypothesized that
      continuous local infusion of OP-1 (BMP-7) would increase local bone formation in
      the presence of two different adverse stimuli, polyethylene particles, and an
      oral NSAID. The Drug Test Chamber (DTC) was implanted in the proximal tibia of
      mature rabbits. The tissue growing into the chamber was exposed to OP-1 solution
      (110 ng/day), which was infused via an osmotic pump. Infusion of OP-1 alone for 6
      weeks enhanced local bone formation in the chamber by 80% (p < 0.05) over
      infusion of carrier alone. In the presence of polyethylene particles, infusion of
      OP-1 increased local bone formation by 38% (p < 0.05) over treatment with
      particles and carrier. Oral administration of NSAID reduced local bone formation
      by 58% (p < 0.05); this suppressive effect caused by NSAIDS was completely
      reversed by the infusion of OP-1 (p < 0.05). These findings underline a potential
      role for local treatment with OP-1 to increase bone formation in the presence of
      potentially adverse stimuli such as polyethylene wear particles or NSAID use.

PMID- 16988978
TI  - Abstracts of the 35th Annual Meeting of the Child Neurology Society, October 18
      21, 2006, Pittsburgh, Pennsylvania, USA.

PMID- 16988977
TI  - Abstracts of the 131st Annual Meeting of the American Neurological Association,
      October 8-11, 2006, Chicago, Illinois, USA.

PMID- 16988986
TI  - External anal sphincter contraction during cough: not a simple spinal reflex.
AB  - AIMS: To assess whether the anal contraction during voluntary coughing is a
      simple spinal reflex-mediated activity or not. To address this question we
      studied the external intercostal (EIC) muscle activity and external anal
      sphincter (EAS) response to cough. MATERIALS AND METHODS: Electromyographic
      recordings were made from pre-gelled disposable surface electrodes. EAS
      electromyographic recordings were made from the EAS of the pelvic floor in 15
      continent women all suffering from urgency and/or frequency without urge or
      stress urinary incontinence, and referred for urodynamic investigation.
      Electromyographic signal was immediately integrated (EMGi). The abdominal
      pressure was recorded with bladder and rectal pressure. EAS EMGi was recorded
      during successive voluntary cough. In three women, we have also recorded EIC EMGi
      activity since it is synchronous with diaphragmatic EMG activity during cough
      initiation. RESULTS: In all subjects, EAS EMGi activity precedes the onset of the
      abdominal pressure increase. The mean latency of EAS EMGi was 615 msec (+/-278).
      In the three subjects whose EMGi activity was recorded both on EAS and EIC, the
      onset of EAS EMGi activity occurred before the EIC EMGi activity (latency ranging
      from 40 to 780 msec) and before the increase in the abdominal pressure.
      CONCLUSIONS: The present study suggests that during coughing, EAS EMG activity
      increases before external intercostal muscle EMGi activity. The contraction of
      the EAS preceding the activation of muscles involved in coughing indicates that
      this response is not a result of a simple spinal reflex, but more likely the
      result of a more intricate reflex involving complex integrative centers.

PMID- 16988988
TI  - No association between occupational exposure to ELF magnetic field and urinary 6
      sulfatoximelatonin in workers.
AB  - A suppression in melatonin secretion is one of the mechanisms proposed to explain
      the possible adverse effects of extremely low frequency magnetic fields (ELF-MF),
      but the results of research are inconclusive. This study investigated the effect
      of occupational ELF-MF exposure on 6-sulfatoximelatonin (6-OHMS). Exposure was
      monitored for three complete work shifts in 59 workers using personal exposure
      meters. Environmental exposure was also evaluated. Urinary 6-OHMS in morning
      samples, an indicator of night-time melatonin production, was measured. Urine was
      collected twice on Friday and the following Monday. Workers were classified
      according to ELF exposure as low exposed (<or=0.2 microT) or higher exposed (>0.2
      microT): 6-OHMS did not differ between groups (P > .05) in either Friday or
      Monday urine samples. In addition, 6-OHMS was not related to exposure under
      multivariate analysis. The ratio between 6-OHMS in Monday versus Friday samples
      was also calculated to test the hypothesis of a possible variation in pineal
      function after 2 days, interruption of occupational ELF-MF exposure: again no
      exposure-related difference was observed. Our results do not support the
      hypothesis that occupational exposure to ELF-MF significantly influences
      melatonin secretion.

PMID- 16988989
TI  - BEMS, WHO, and the precautionary principle.

PMID- 16988990
TI  - Effects of magnetic field on the antioxidant enzyme activities of suspension
      cultured tobacco cells.
AB  - Effects of magnetic fields (MFs) on the activities of antioxidant enzymes of
      suspension-cultured tobacco cells were investigated. Compared with the control
      cells, exposure of the cells to static MF with the magnitudes of 10 and 30 mT for
      5 days, 5 h each day, increased the activity of superoxide dismutase (SOD). In
      contrast, the activity of the catalase (CAT) and ascorbate peroxidase (APX) was
      decreased by MF, compared with those of the control cells. Level of lipid
      peroxidation was also increased by MF. It suggests that MF could deteriorate
      antioxidant defense system of plant cells.

PMID- 16988991
TI  - Influence of pH, temperature, and urea molar flowrate on Arthrospira platensis
      fed-batch cultivation: a kinetic and thermodynamic approach.
AB  - Arthrospira platensis was cultivated photoautotrophically at 6.0 klux light
      intensity in 5.0-L open tanks, using a mineral medium containing urea as nitrogen
      source. Fed-batch experiments were performed at constant flowrate. A central
      composite factorial design combined to response surface methodology (RSM) was
      utilized to determine the relationship between the selected response variables
      (cell concentration after 10 days, X(m), cell productivity, P(X), and nitrogen-to
      cell conversion factor, Y(X/N)) and codified values of the independent variables
      (pH, temperature, T, and urea flowrate, K). By applying the quadratic regression
      analysis, the equations describing the behaviors of these responses as
      simultaneous functions of the selected independent variables were determined, and
      the conditions for X(m) and P(X) optimization were estimated (pH 9.5, T = 29
      degrees C, and K = 0.551 mM/day). The experimental data obtained under these
      conditions (X(m) = 749 mg/L; P(X) = 69.9 mg/L.day) were very close to the
      estimated ones (X(m) = 721 mg/L; P(X) = 67.1 mg/L.day). Additional cultivations
      were carried out under the above best conditions of pH control and urea flowrate
      at variable temperature. Consistently with the results of RSM, the best growth
      temperature was 29 degrees C. The maximum specific growth rates at different
      temperatures were used to estimate the thermodynamic parameters of growth
      (DeltaH* = 59.3 kJ/mol; DeltaS* = -0.147 kJ/mol.K; DeltaG* = 103 kJ/mol) and its
      thermal inactivation (DeltaH(D) (o) = 72.0 kJ/mol; DeltaS(D) (o) = 0.144
      kJ/mol.K; DeltaG(D) (o) = 29.1 kJ/mol).

PMID- 16988992
TI  - Survey of residential 50 Hz EMF exposure from transformer stations.
AB  - In Hungary it is typical that 10/04 kV transformer stations are being installed
      in multistory residential and office buildings. Magnetic fields (MFs) up to
      several tens of microT have been measured in apartments close to transformers.
      The aim of the present study was to provide systematic assessment of MF exposure
      of residents living above transformer stations. Out of 41 addresses provided by
      the electricity supplier, current load of 21 transformers and MF in 21 apartments
      was measured. Spot MFs at 1 m height and time weighted average 24 h MF exposure
      at bed height was measured. All-day personal MF exposure was measured at waist
      and HOME exposure was calculated. BED exposure was measured at bed height.
      Participants kept a time-activity diary. The time-weighted average 24 h MF
      exposure (3.03 microT) exceeded the usual residential exposure (<0.2 microT). The
      mean HOME and BED personal exposure above transformers was 0.825 and 1.033
      microT, respectively. Our study provides exposure assessment of a cohort with a
      wider exposure range, compared to power-line epidemiological studies.

PMID- 16988993
TI  - Effects of information and 50 Hz magnetic fields on cognitive performance and
      reported symptoms.
AB  - The aim of this study was to explore the role of expectancies and beliefs about
      the potential effects of electromagnetic fields (EMFs) (what the subject thought
      the effect was going to be) and the effects of 50 Hz magnetic fields (400
      microT(rms)) acute exposure on cognitive performance, the reporting of physical
      symptoms and some psychological and physiological parameters. Seventy-four
      healthy male volunteers aged between 40 and 60 years of age were randomly
      assigned to one of five groups, which differed in (1) the type of information
      they were given concerning the expected magnetic field effect on performance in
      cognitive tests (positive = enhancement of the performance; negative = impairment
      of the performance; neutral) and (2) the type of exposure (real or sham). Three
      groups were sham exposed with positive (group+), negative (group-) and neutral
      information (group+/-); one group was really exposed with neutral information
      (group expo) and one group was not exposed, though they wore the helmet, and did
      not receive any field-related information (control group). All the volunteers,
      except the control group, were led to believe that they would be exposed to a
      magnetic field of 400 microT(rms). The experimental design respected a double
      blind procedure and the experimental session involved three steps (pre-testing,
      exposure, and post-testing). Various measurements were taken, including cognitive
      performance, psychological parameters such as mood, vigilance, and reporting of
      symptoms. Physiological parameters such as blood pressure and pulse rate were
      also recorded. The information given did not significantly modify beliefs. No
      significant difference was found among the five groups depending on the type of
      information and the type of exposure in cognitive performance, psychological and
      physiological parameters. In the context of the study, with our population, the
      type of information given failed to induce expected changes in parameters
      measured. Our results do not support the hypothesis that an acute exposure to
      extremely low frequency magnetic fields (50 Hz, 400 microT(rms)) affects the
      parameters measured.

PMID- 16988995
TI  - The effect of induced biphasic pulsed currents on re-epithelialization of a novel
      wound healing model.
AB  - The coordinated migration of keratinocytes is crucial to cutaneous wound healing;
      failure of keratinocytes to migrate into a wound can lead to chronic non-healing
      wounds. Keratinocyte migration can be influenced by applied electrical fields.
      Our aim was to investigate whether keratinocyte migration could be accelerated by
      applying an induced biphasic pulsed electrical field. We developed two in vitro
      biological systems models for this purpose: a keratinocyte colony-forming model
      and a reconstituted skin wound healing model with biphasic pulsed currents. Our
      in vitro skin models were capable of generating trans-epithelial potentials (TEP)
      similar to in vivo mammalian skin. Histological examination of the wound healing
      model also indicated that re-epithelialization occurred in a similar manner to
      that seen in vivo, although no evidence of a reconstitution of a basement
      membrane was seen during the 14 days in vitro experimental period. We found that
      growth of keratinocyte colonies and keratinocyte migration in an in vitro wound
      bed were not significantly affected by induced short duration biphasic pulsed
      currents at a frequency of 0.5 Hz of 100 and 200 mV/mm.

PMID- 16988996
TI  - A pilot investigation of the effect of extremely low frequency pulsed
      electromagnetic fields on humans' heart rate variability.
AB  - The question whether pulsed electromagnetic field (PEMF) can affect the heart
      rhythm is still controversial. This study investigates the effects on the
      cardiocirculatory system of ELF-PEMFs. It is a follow-up to an investigation made
      of the possible therapeutic effect ELF-PEMFs, using a commercially available
      magneto therapeutic unit, had on soft tissue injury repair in humans. Modulation
      of heart rate (HR) or heart rate variability (HRV) can be detected from changes
      in periodicity of the R-R interval and/or from changes in the numbers of heart
      beat/min (bpm), however, R-R interval analysis gives only a quantitative insight
      into HRV. A qualitative understanding of HRV can be obtained considering the
      power spectral density (PSD) of the R-R intervals Fourier transform. In this
      study PSD is the investigative tool used, more specifically the low frequency
      (LF) PSD and high frequency (HF) PSD ratio (LF/HF) which is an indicator of
      sympatho-vagal balance. To obtain the PSD value, variations of the R-R time
      intervals were evaluated from a continuously recorded ECG. The results show a HR
      variation in all the subjects when they are exposed to the same ELF-PEMF. This
      variation can be detected by observing the change in the sympatho-vagal
      equilibrium, which is an indicator of modulation of heart activity. Variation of
      the LF/HF PSD ratio mainly occurs at transition times from exposure to
      nonexposure, or vice versa. Also of interest are the results obtained during the
      exposure of one subject to a range of different ELF-PEMFs. This pilot study
      suggests that a full investigation into the effect of ELF-PEMFs on the
      cardiovascular system is justified.

PMID- 16988997
TI  - Magnetic field exposure and prognostic factors in childhood leukemia.
AB  - We examined the association between magnetic field (MF) exposure and the presence
      of prognostic risk factors among 482 children diagnosed with acute lymphoblastic
      leukemia (ALL) between 1996 and 2001. Personal 24-h MF measurements were obtained
      for 412 children; 386 children were included in analyses. There were no trends
      seen between increasing exposure to MF and the presence of adverse clinical and
      tumor-specific prognostic factors. Our results suggest that exposure to MF is not
      associated with the presence of unfavorable cytogenetic abnormalities in leukemic
      blast cells or with clinical factors at the time of diagnosis that predict poor
      survival.

PMID- 16988998
TI  - A comparison of the prevalence of urinary incontinence in girls with cystic
      fibrosis, asthma, and healthy controls.
AB  - Urinary incontinence (UI) is recognized as a significant problem in adult females
      with cystic fibrosis and can often have a marked impact on day-to-day activities.
      The prevalence and severity of UI in the pediatric cystic fibrosis (CF) female
      population is less clear and there are no comparative data with healthy children
      or children with other respiratory disorders. An anonymous self-completed semi
      structured questionnaire was used to study the prevalence rates of UI in girls
      with CF aged between 11 and 17 and compared it to age-matched asthmatic and
      healthy girls. The prevalence of UI in girls with CF was significantly higher
      (17/51, 33%) than the asthmatic (4/25, 16%) and healthy girls (2/27, 7%) (P =
      0.02). It may manifest as early as 11 years of age and is associated with
      increasing lung disease. Surprisingly it is perceived as a relatively minor
      problem in terms of the distress it causes. Pediatric CF clinics should be
      routinely addressing UI as a potential problem in all girls from the age of 11
      years.

PMID- 16988999
TI  - Molecular and functional changes of pulmonary surfactant in response to
      hyperoxia.
AB  - Surfactant comprises phosphatidylcholine (PC) together with anionic
      phospholipids, neutral lipids, and surfactant proteins SP-A to-D. Its composition
      is highly specific, with dipalmitoyl-PC, palmitoyl-myristoyl-PC, and palmitoyl
      palmitoleoyl-PC as its predominant PC species, but with low polyunsaturated
      phospholipids. Changes in pulmonary metabolism and function in response to
      injuries depend on their duration and whether adaptation can occur. We examined
      in rats prolonged (7 days) versus acute (2 days) exposure to non-lethal oxygen
      concentrations (85%) with respect to the composition and metabolism of individual
      lung phospholipid molecular species. Progressive inflammation, structural
      alteration, and involvement of type II pneumocytes were confirmed by augmented
      bromodeoxyuridine incorporation, broadening of alveolar septa, and increased
      granulocyte, macrophage, SP-A, and SP-D concentrations. Surfactant function was
      impaired after 2 days, but normalized with duration of hyperoxia, which was
      attributable to inhibition but not to alteration in SP-B/C concentrations.
      Phospholipid pool sizes and PC synthesis by lung tissue, as assessed by [methyl
      (3)H]-choline incorporation, were unchanged after 2 days, although after 7 days
      they were elevated 1.7-fold. By contrast, incorporation of labeled PC into tissue
      pools of surfactant and lung lavage fluid decreased progressively. Moreover,
      concentrations of arachidonic acid containing phospholipids were augmented at the
      expense of saturated palmitoyl-myristoyl-PC and dipalmitoyl-PC. We conclude a
      persisting impairment in the intracellular trafficking and secretion of newly
      synthesized PC, accompanied by a progressive increase in alveolar arachidonic
      acid containing phospholipids in spite of recovery of acutely impaired surfactant
      function and adaptive increase of overall PC synthesis.

PMID- 16989001
TI  - Assessment of inhalation technique and determinants of incorrect performance
      among children with asthma.
AB  - The objective of our study was to evaluate the pressurized metered dose inhaler
      (pMDI) with holding chamber technique of asthmatic children attending out patient
      pediatric chest clinic and determine factors associated with incorrect technique.
      All patients had previously received instructions regarding inhalation technique.
      The inhalation technique was assessed on a five-point checklist, four of which
      were considered essential. Two hundred and thirteen children (mean +/- SD age,
      7.3 +/- 3.8 years; 151 boys) completed the study. Children were using their
      inhaler for a median duration of 6 months (range 1-96 months). One hundred and
      eighty-eight patients (88.3%) performed all essential steps correctly. The
      commonest mistake among the essential steps was not shaking the inhaler (n = 21,
      9.9%) followed by inability to make a tight seal around the mouthpiece of the
      holding chamber (n = 12, 5.6%). Correct technique was not affected by gender,
      asthma severity and socio-economic indices: education level of parents, percapita
      monthly income, rural or urban background. Our study indicates that a large
      majority of children from a developing country setting, irrespective of lower
      education and income levels can be successfully educated to appropriately use
      inhalation device. Inhalation performance is not affected by socio-economic
      background of the patients. Comprehensive inhalation instructions and monitoring
      at each visit are however critical to ensure reliable and consistent performance
      of correct technique among asthmatic children.

PMID- 16989002
TI  - Survival outcome and predictors of gefitinib antitumor activity in East Asian
      chemonaive patients with advanced nonsmall cell lung cancer.
AB  - BACKGROUND: Chemonaive patients had higher response rates than chemotherapy
      treated patients in previous analyses of East Asian patients with advanced
      nonsmall cell lung cancer. The survival outcome and the predictors for antitumor
      activity in chemonaive patients who received gefitinib as first-line treatment
      are unclear. METHODS: Clinicopathologic predictive factors, objective tumor
      responses, and the survival of consecutive patients with advanced, chemonaive
      nonsmall cell lung cancer who received gefitinib as first-line treatment were
      collected and analyzed. Multivariate analysis was conducted to determine
      independent predictive factors for gefitinib antitumor efficacy. RESULTS: One
      hundred ninety-six patients (112 males and 84 females) were analyzed. Ninety-six
      patients (49%) were never smokers. One hundred forty-four patients (73%) had
      adenocarcinoma or bronchioloalveolar carcinoma histology. One hundred twenty
      patients had an Eastern Cooperative Oncology Group performance status 0 to 2.
      Eighty-three patients (42%; 95% confidence interval, 36-49%) had an objective
      tumor response. An additional 35 patients had stable disease (disease control
      rate, 61%). The tumor response rate was 52% in patients who had a good
      performance status. Female gender, nonsmoking status, and adenocarcinoma
      histology all were independent predictors of response or disease control in
      multivariate analysis. The median survival was 11.1 months, and the 1-year
      survival rate of patients who had a good performance status was 47.5%.
      CONCLUSIONS: The response rate to gefitinib was high in East Asian chemonaive
      patients with advanced nonsmall cell lung cancer. Female gender, adenocarcinoma
      histology, and nonsmoking status all were independent predictors of gefitinib
      response. The survival outcome of these patients was similar to that of patients
      who initially received chemotherapy.

PMID- 16989003
TI  - Estimating national drug consumption using data at different points in the
      pharmaceutical supply chain.

PMID- 16989004
TI  - Screening new cancer patients for psychological distress using the hospital
      anxiety and depression scale.
AB  - The diagnosis of a life-threatening illness creates immediate psychosocial
      distress for the patient and his or her family. The threat is real and the
      rational response is to be afraid. We need to be reaching out to patients and
      their families and not waiting for crises. The responsibility remains with the
      healthcare system and psychosocial healthcare professionals to identify those who
      are in most need. Psychological distress is something that can be relatively
      easily measured and responded to when psychosocial oncology healthcare
      professionals are immediately available to address those needs. This paper
      describes the process used to gather this information, how that information has
      been used by the psychosocial clinicians in the Supportive Care programme, and
      what we have learned, in terms of a retrospective data analysis, about our
      patient population. At the Cancer Centre in Thunder Bay, Ontario, Canada new
      cancer patients complete the HADS on the day of their first appointment. Since
      October 2000 we have collected baseline psychological distress data for 3,035 new
      cancer patients who fully completed all 14 items on the HADS. Of those, 781
      patients, or 25.7%, scored above cut-off points and were given a telephone call.
      We were able to contact 607 (or 77.7%) of these patients. Five hundred and eight
      (or 83.7%) of those contacted made, and subsequently attended, one or more
      appointments with a psychosocial counsellor.

PMID- 16989005
TI  - Homologous recombination-mediated double-strand break repair in mouse testicular
      extracts and comparison with different germ cell stages.
AB  - Homologous recombination (HR) is established as a significant contributor to
      double-strand break (DSB) repair in mammalian somatic cells; however, its role in
      mammalian germ cells has not been characterized, although being conservative in
      nature it is anticipated to be the major pathway in germ cells. The germ cell
      system has inherent limitations by which intact cell approaches are not feasible.
      The present study, therefore, investigates HR-mediated DSB repair in mouse germ
      cell extracts by using an in vitro plasmid recombination assay based on
      functional rescue of a neomycin (neo) gene. A significantly high-fold increase in
      neo+ (Kan(R)) colonies following incubation of two plasmid substrates (neo delta1
      and neo delta2) with testicular extracts demonstrated the extracts' ability to
      catalyze intermolecular recombination. A significant enhancement in recombinants
      upon linearization of one of the plasmids suggested the existence of an HR
      mediated DSB repair activity. Comparison of the activity at sequential
      developmental stages, spermatogonia, spermatocytes and spermatids revealed its
      presence at all the stages; spermatocyte being the most proficient stage.
      Further, restriction analysis of recombinant plasmids indicated the predominance
      of gene conversion in enriched spermatocytes (mostly pachytenes), in contrast to
      gonial and spermatid extracts that showed higher reciprocal exchange. In
      conclusion, this study demonstrates HR repair activity at all stages of male germ
      cells, suggesting an important role of HR-mediated DSB repair during mammalian
      spermatogenesis. Further, the observed preference of gene conversion over
      reciprocal exchange at spermatocyte stage correlates with the close association
      of gene conversion with the meiotic recombination program.

PMID- 16989006
TI  - Improved HSV-1 amplicon packaging using virion host shutoff mutants lacking
      mRNAse activity.
AB  - Given their generous transgene capacity and inherent neurotropism, herpes simplex
      virus (HSV-1)-based viral vectors are promising tools for gene delivery to the
      central nervous system. Despite their widespread pre-clinical use, vector
      toxicity remains a concern with regard to the use of herpes vectors in humans.
      One potential source of toxicity stems from the tegument-associated virion host
      shutoff protein (vhs), which induces translational arrest in the host cell
      through non-specific mRNAse activity. In the current study we utilized a series
      of HSV-1 viruses containing a deletion in the U(L)41 open reading frame to
      investigate: (1) the requirement of intact vhs function in amplicon packaging and
      (2) whether vhs influences the post-transduction survival of dissociated cortical
      neurons. Our results demonstrate that while amplicon yield was reduced an order
      of magnitude, U(L)41 deletion was associated with reduced vector toxicity.
      Furthermore, partial reconstitution of vhs function using mRNAse-inactive point
      mutants improved amplicon titers without imparting the toxicity observed with
      wild-type controls. These findings offer a novel approach to improving the titer
      and toxicity profiles of HSV-based viral vectors.

PMID- 16989007
TI  - Determination of ketamine and norketamine in hair by gas chromatography/mass
      spectrometry using two-step derivatization.

PMID- 16989008
TI  - Transplantation of bone marrow genetically engineered to express proinsulin II
      protects against autoimmune insulitis in NOD mice.
AB  - BACKGROUND: Type 1 diabetes (T1D) is a T-cell-dependent autoimmune disease
      resulting from destructive inflammation (insulitis) of the insulin-producing
      pancreatic beta-cells. Transgenic expression of proinsulin II by a MHC class II
      promoter or transfer of bone marrow from these transgenic mice protects NOD mice
      from insulitis and diabetes. We assessed the feasibility of gene therapy in the
      NOD mouse as an approach to treat T1D by ex vivo genetic manipulation of normal
      hematopoietic stem cells (HSCs) with proinsulin II followed by transfer to
      recipient mice. METHODS: HSCs were isolated from 6-8-week-old NOD female mice and
      transduced in vitro with retrovirus encoding enhanced green fluorescent protein
      (EGFP) and either proinsulin II or control autoantigen. Additional control groups
      included mice transferred with non-manipulated bone marrow and mice which did not
      receive bone marrow transfer. EGFP-sorted or non-sorted HSCs were transferred
      into pre-conditioned 3-4-week-old female NOD mice and insulitis was assessed 8
      weeks post-transfer. RESULTS: Chimerism was established in all major lymphoid
      tissues, ranging from 5-15% in non-sorted bone marrow transplants to 20-45% in
      EGFP-sorted bone marrow transplants. The incidence and degree of insulitis was
      significantly reduced in mice receiving proinsulin II bone marrow compared to
      controls. However, the incidence of sialitis in mice receiving proinsulin II bone
      marrow and control mice was not altered, indicating protection from insulitis was
      antigen specific. CONCLUSIONS: We show for the first time that ex vivo genetic
      manipulation of HSCs to express proinsulin II followed by transplantation to NOD
      mice can establish molecular chimerism and protect from destructive insulitis in
      an antigen-specific manner.

PMID- 16989009
TI  - Hydrocarbon bond dissociation enthalpies: from substituted aromatics to large
      polyaromatics.
AB  - Hydrocarbon-bond dissociation enthalpies (BDE) at 298 K are calculated for a set
      of hydrocarbons. An efficient method for calculating the BDE values is derived on
      the basis of a comparative study with experimental data. The methods considered
      are based on density functional theory (DFT) including the B3LYP, MPW1PW91,
      B3P86, B3PW91, MPW1P86, KMLYP, MPW1K and BMK functionals. The commonly known
      sequence for radical stability is quantified on the basis of BDE values. The
      recommended procedure is extrapolated to substituted aromatics and large
      polyaromatic hydrocarbons (PAHs) to obtain insight into the factors that govern
      the stability of the radicals. Furthermore it is shown that BDEs are also good
      reactivity descriptors for subsequent additions involving the formed radicals.
      Linear correlations, similar to classical Evans-Polanyi-Semenov plots, between
      the BDE and the reaction barriers for addition reactions with ethene, ethyne,
      propene, propyne and butadiene are found, as the exothermicity is primarily
      determined by the stability of the originating reactant radical.

PMID- 16989010
TI  - The N3+ reactivity in ionized gases containing sulfur, nitrogen, and carbon
      oxides.
AB  - The N(3)(+) reactivity with SO(2), N(2)O, CO(2), and CO is studied by mass
      spectrometric techniques under a wide range of pressures from 10(-7) to 10(-4)
      Torr. The kinetics, reaction mechanism, and role of vibrationally excited ions
      are investigated by experimental and theoretical methods. Key distinguishing
      features of the N(3) (+) reactivity are evidenced by comparison to N(+) and
      N(2)(+) ions, which mainly undergo charge-exchange reactions. The N(+) transfer
      to SO(2) prompts formation of NO(+) ions and neutral oxides NO and SO. The N(+)
      transfer to N(2)O also leads to NO(+) ions by a process not allowed by spin
      conservation rules. In both cases no reaction intermediate is detected, whereas
      CO(2) and CO are captured to form the very stable NCO(2) (+) and NCO(+) ions.
      NCO(2)(+) ions are characterized for the first time as strongly bound triplet
      ions of NOCO and ONCO connectivity. DFT and CCSD(T) computations have been
      carried out to investigate the structural and energetic features of the NCO(2)
      (+) species and their formation process.

PMID- 16989011
TI  - Randomized clinical trial of single-dose antibiotic prophylaxis for non
      reconstructive breast surgery.
AB  - BACKGROUND: The aim of this randomized clinical trial was to determine whether a
      single intravenous dose of 2 g flucloxacillin could prevent wound infection after
      primary non-reconstructive breast surgery. METHODS: The study included 618
      patients undergoing local excision (n = 490), mastectomy (n = 107) or
      microdochectomy (n = 21). Patients were randomized to receive either a single
      dose of flucloxacillin immediately after the induction of anaesthesia or no
      intervention. Wound morbidity was monitored by an independent research nurse for
      42 days after surgery. RESULTS: The incidence of wound infection was similar in
      the two groups: 10 of 311 (3.2 percent) in the flucloxacillin group and 14 of 307
      (4.6 percent) in the control group (chi(2) = 0.75, P = 0.387; relative risk 0.71,
      95 percent confidence interval 0.32 to 1.53). The groups also had similar wound
      scores and rates of moderate or severe cellulitis. Wound infection presented a
      median of 16 days after surgery. CONCLUSION: The administration of a single dose
      of flucloxacillin failed to reduce the rate of wound infection after non
      reconstructive breast surgery.

PMID- 16989012
TI  - Natural killer cells play a key role in the antitumor immunity generated by
      chaperone-rich cell lysate vaccination.
AB  - Tumor derived chaperone-rich cell lysate (CRCL) when isolated from tumor tissues
      is a potent vaccine that contains at least 4 of the highly immunogenic heat shock
      proteins (HSP) such as HSP70, HSP90, glucose related protein 94 and calreticulin.
      We have previously documented that CRCL provides both a source of tumor antigens
      and danger signals triggering dendritic cell (DC) activation. Immunization with
      tumor derived CRCL elicits tumor-specific T cell responses leading to tumor
      regression. In the current study, we further dissect the mechanisms by which CRCL
      simulates the immune system, and demonstrate that natural killer (NK) cells are
      required for effective antitumor effects to take place. Our results illustrate
      that CRCL directly stimulates proinflammatory cytokine and chemokine production
      by NK cells, which may lead to activation and recruitment of macrophages at the
      tumor site. Thus, this report provides further insight into the function of CRCL
      as an immunostimulant against cancer.

PMID- 16989014
TI  - Sensitivity of the acid-base properties of clays to the methods of preparation
      and measurement.     1. Literature review.
AB  - Measuring and modeling the surface charge of clays, and more especially
      smectites, has become an important issue in the use of bentonites as a waste
      confinement material aimed at retarding migration of water and solutes.
      Therefore, many studies of the acid-base properties of montmorillonite have
      appeared recently in the literature, following older studies principally devoted
      to cation exchange. It is striking that beyond the consensus about the complex
      nature of the surface charge of clays, there are many discrepancies, especially
      concerning the dissociable charge, that prevents intercomparison among the
      published data. However, a general trend is observed regarding the absence of
      common intersection point on raw titration curves at different ionic strengths.
      Analysis of the literature shows that these discrepancies originate from the
      experimental procedures for the preparation of the clays and for the
      quantification of their surface charge. The present work is an attempt to
      understand how these procedures can impact the final results. Three critical
      operations can be identified as having significant effects on the surface
      properties of the studied clays. The first one is the preparation of purified
      clay from the raw material: the use of acid or chelation treatments, and the
      repeated washings in deionized water result in partial dissolution of the clays.
      Then storage of the purified clay in dry or wet conditions strongly influences
      the equilibria in the subsequent experiments respectively by precipitation or
      enhanced dissolution. The third critical operation is the quantification of the
      surface charge by potentiometric titration, which requires the use of strong
      acids and bases. As a consequence, besides dissociation of surface sites, many
      secondary titrant consuming reactions were described in the literature, such as
      cation exchange, dissolution, hydrolysis, or precipitation. The cumulated effects
      make it difficult to derive proper dissociation constants, and to build adequate
      models. The inadequation of the classical surface complexation models to describe
      the acid-base behavior of clays is illustrated by the electrokinetic behavior of
      smectites, which is independent from the pH and the ionic strength. Therefore,
      there is still a need on one hand for accurate data recorded in controlled
      conditions, and on the other hand for new models taking into account the complex
      nature of the charge of clays.

PMID- 16989015
TI  - [Age-related macular degeneration].

PMID- 16989016
TI  - [Acupuncture therapy against pain].

PMID- 16989017
TI  - Peptidergic sensory and parasympathetic fiber sprouting in the mucosa of the rat
      urinary bladder in a chronic model of cyclophosphamide-induced cystitis.
AB  - In this study, we used a well-established animal model to investigate changes in
      the peptidergic and parasympathetic innervation of the bladder following chronic
      bladder inflammation. Adult female Sprague-Dawley rats were injected with either
      70 mg/kg cyclophosphamide diluted in saline, i.p., once every 3 days or saline.
      After 10 days, all animals were tested for urinary frequency and number of low
      volume voids, as well as symptoms of spontaneous pain. At the end of 12 days, all
      animals were perfused with histological fixatives and the urinary bladders
      processed for immunofluorescence using antibodies against calcitonin gene-related
      peptide and the vesicular acetylcholine transporter as markers, respectively, of
      peptidergic primary afferent fibers and parasympathetic efferent fibers. We show
      that animals treated with cyclophosphamide had inflamed bladders and displayed
      high urinary frequency as well as some indicators of spontaneous pain, such as
      piloerection and a rounded-back posture. Furthermore, they had a significant
      increase in the density of both parasympathetic and peptidergic sensory fibers in
      the bladder mucosa and an increase in peptidergic sensory fibers in the detrusor
      muscle. Based on these results, we suggest that peripheral sprouting of
      parasympathetic and peptidergic fibers could be a mechanism responsible for
      sensitization of the bladder, leading to urinary symptoms. Since we observed that
      the parasympathetic and peptidergic fibers often wrapped around one another and
      that their varicosities were very close, these two fiber populations may be
      interacting with each other to lead to and maintain sensitization. Future studies
      are required to establish the role of this fiber sprouting in bladder symptoms.

PMID- 16989018
TI  - [Quality control in the use of urocultures in cases with a high risk of renal
      colonisation].

PMID- 16989019
TI  - Night eating syndrome (NES).

PMID- 16989020
TI  - Re: Recent advances in the treatment of borderline personality disorder.

PMID- 16989022
TI  - Proceedings of the 2004 Joint Meeting of the Society of Forensic Toxicologists
      and the International Association of Forensic Toxicologists. August 30-September
      3, 2004. Washington, D.C., USA.

PMID- 16989021
TI  - Less than one-quarter of California adults walk regularly.
AB  - This policy brief presents information about the walking habits of California
      adults based on data from the 2003 California Health Interview Survey (CHIS
      2003). We examine the prevalence of regular walking and no walking by socio
      demographic and neighborhood characteristics. Regular walking is defined as
      walking on at least five separate occasions for a combined total of at least 150
      minutes in the previous seven days. This definition is based on the
      recommendation that adults engage in moderate physical activity for at least 30
      minutes on five or more days of the week. Occasional walking is defined as
      walking at least once for 10 or more minutes in the previous seven days. No
      walking is defined as not walking at least once for 10 or more minutes in the
      previous seven days.

PMID- 16989023
TI  - Pegaptanib: new drug. In macular degeneration: too many risks for too little
      benefit.
AB  - (1) Age-related macular degeneration with vascular proliferation can markedly
      hamper vision. In patients with subfoveolar involvement, verteporfin photodynamic
      therapy slows the loss of visual acuity on the EDTRS scale in about 15% of
      patients after 2 years of follow-up. (2) Pegaptanib, a vascular endothelial
      growth factor (VEGF) inhibitor, has been approved for the treatment of the
      neovascular form of age-related macular degeneration. (3) Two double-blind
      placebo-controlled trials involved a total of 1208 patients. When pegaptanib was
      injected into the eye every 6 weeks, at a dose of 0.3 mg, visual loss measured
      one year after beginning treatment was slowed in about 15% more patients on
      pegaptanib than on placebo. Efficacy during the second year is uncertain.
      Pegaptanib has not been compared with other treatments, nor has it been assessed
      in combination with verteporfin. (4) A variety of ocular adverse events were
      reported during clinical trials, three of which were serious and each affected
      about 1% of patients: endophthalmia, retinal detachment, and cataracts. Transient
      ocular hypertension occurred in about 15% of patients. A few cases of retinal
      arterial and venous thrombosis have been described. No long-term adverse effects
      were reported after clinical trials, but hypersensitivity reactions were reported
      post-approval. (5) Treatment with pegaptanib involves an intraocular injection
      every 6 weeks under local anaesthesia and under conditions of surgical asepsis.
      (6) In practice, an indirect comparison suggests that intraocular pegaptanib is
      no more effective than verteporfin photodynamic therapy. In contrast, adverse
      events are more numerous and treatment is less convenient.

PMID- 16989024
TI  - Imiquimod: new indication. Basal cell carcinoma: inferior to other treatments.
AB  - (1) Basal cell carcinoma is a common malignancy that is rarely life-threatening.
      The aim of treatment is to remove the tumour and prevent local recurrences.
      Surgical excision is the standard treatment, with a mean relapse rate of about 5%
      at 5 years. The main alternative is radiotherapy. (2) The Indications section of
      the Summary of Product Characteristics (SPC) for imiquimod cream in Europe now
      includes "topical treatment of small superficial basal cell carcinomas in
      adults". (3) Imiquimod cream was primarily evaluated in 2 double-blind randomised
      controlled trials versus excipient, in a total of 724 patients. In these trials,
      small basal cell tumours (maximum 2 cm in diameter) disappeared in three-quarters
      of patients after imiquimod application 5 or 7 days a week for six weeks. (4) A
      non comparative trial involving 143 patients showed a relapse rate of 21% at 2
      years. Indirect comparisons show that this is a much higher relapse rate than
      after other well-assessed treatments for basal cell cancer. (5) During clinical
      trials, nearly one-third of patients who used imiquimod 5 times a week complained
      of pruritus, a burning sensation, or local pain. Nearly one-half of patients
      experienced these problems with daily use. (6) Imiquimod cream is relatively
      inconvenient to use: it has to be applied in the evening; residual cream must be
      removed the following morning; and baths, showers and direct sunlight must be
      avoided during treatment.

PMID- 16989026
TI  - Reversible Parkinsonism linked to trimetazidine (continued).
AB  - (1) In a series of 128 neurological patients taking trimetazidine, 56 developed
      motor disorders that improved or resolved when trimetazidine was withdrawn. (2)
      New cases of parkinsonism, gait disorders and tremor that resolved or improved
      after trimetazidine withdrawal have been reported in France. (3) As there is no
      evidence that trimetazidine is effective, there is no justification for placing
      patients at risk for parkinsonism. (4) Patients who develop motor disorders while
      taking trimetazidine have everything to gain and nothing to lose by discontinuing
      treatment. There is no possible justification for initiating treatment with
      trimetazidine.

PMID- 16989025
TI  - Topiramate: new indication. Migraine prevention: best avoided.
AB  - (1) The first-line drug for prevention of migraines is propranolol: it is the
      most thoroughly evaluated treatment, and thus far no other drug has been found to
      be more effective. (2) Topiramate, an antiepileptic drug, is now also approved
      for migraine prevention. Only 3 out of 4 double-blind placebo-controlled trials
      showed that topiramate 100 mg/day was effective: on average, 46% of patients had
      a reduction of at least 50% in the frequency of migraines, compared to 23% of
      patients on placebo. Increasing the dose to 200 mg did not lead to better
      efficacy. (3) A double-blind trial versus propranolol failed to show that
      topiramate was as effective or better than propranolol. (4) Topiramate has
      numerous, frequent and sometimes serious adverse effects, mainly including
      neurosensory disorders (paraesthesias, language disorders, confusion) and
      gastrointestinal disturbances. (5) Topiramate treatment costs nearly 5 times more
      than propranolol. (6) In practice, the adverse effects of topiramate outweigh its
      efficacy in the prevention of migraine attacks.

PMID- 16989027
TI  - Hormone replacement therapy aggravates postmenopausal urinary incontinence.
AB  - (1) In the WHI trials, which involved more than 20 000 women, the frequency of
      urinary incontinence increased among postmenopausal women taking hormone
      replacement therapy compared with placebo. Among women who were continent at
      enrollment, the frequency of stress incontinence at 1 year was 16% with an
      oestrogen-progestin combination, compared with 9% with placebo (relative risk
      1.87, 95% confidence interval: 1.61-2.18). Among women who were already
      incontinent, the relative risk of aggravation with hormone replacement therapy
      compared with placebo was about 1.40. (2) The results of another trial involving
      nearly 3000 women were similar. (3) Other, smaller trials failed to show any
      positive impact of oestrogen-progestin therapy on urinary incontinence in
      postmenopausal women. (4) In practice, postmenopausal hormone replacement therapy
      does not protect against urinary incontinence; on the contrary, it may trigger or
      worsen urinary incontinence.

PMID- 16989028
TI  - Methylphenidate: cardiac risks.

PMID- 16989029
TI  - Ibritumomab: serious cutaneous reactions.

PMID- 16989030
TI  - The metabolic syndrome: an artificial and irrelevant notion.
AB  - (1) The term 'metabolic syndrome' was first coined in the 1970s, although initial
      reports of associated lipid and carbohydrate metabolic disorders in the same
      patient date from the 1930s. (2) The metabolic syndrome refers to a variety of
      vaguely related disorders, often including obesity, blood lipid disorders, type 2
      diabetes, and varying degrees of hypertension. Various definitions and diagnostic
      criteria have been proposed. Smoking is not included. (3) A 'diagnosis' of
      'metabolic syndrome' has no clinical or therapeutic relevance. (4) It is better
      to treat each condition, if it is associated with an increased risk of
      cardiovascular disorders, provided a treatment with a positive risk-benefit
      balance (including a proven impact on morbidity/mortality endpoints) is
      available.

PMID- 16989031
TI  - Hairy-cell leukaemia: first-line treatment with cladribine or pentostatin.
AB  - (1) Hairy-cell leukaemia is a chronic lymphoid malignancy occurring in adulthood.
      It is rare and progresses slowly. The median survival time without treatment is
      about 4 years. The main presenting signs are infections and cytopenias (anaemia,
      thrombocytopenia, leukopenia). (2) Treatment is usually based on the purine
      analogues cladribine and pentostatin. About 80% of patients treated with
      cladribine or pentostatin survive for at least 10 years. (3) The main adverse
      effect of these treatments is the risk of infection, especially by Pneumocystis
      and herpes viruses, due to immunosuppression. Secondary cancers are frequent, but
      it is difficult to tell the extent to which these are caused by the disease or
      its treatment. (4) Interferon alfa and splenectomy are generally used when purine
      analogues fail.

PMID- 16989032
TI  - Cranberry and urinary tract infections: slightly fewer episodes in young women,
      but watch out for interactions.
AB  - (1) Female urinary tract infections are common and often recurrent. Food
      supplements based on cranberries are said to prevent recurrent urinary tract
      infections. (2) Two randomised controlled trials involving a total of about 300
      young women showed that daily use of cranberry juice or tablets reduced the
      relapse rate for acute cystitis: on average, treating 100 women for one year
      prevented at least 1 urinary tract infection in 15 to 33 women. The daily doses
      were 7.5 g of concentrate in 50 ml of water, 750 ml of juice, or two tablets of
      concentrate. (3) In elderly patients, 2 trials of cranberry-based products in
      hospitals or nursing homes showed a small reduction in the frequency of relapses.
      (4) Adverse effects appear to be negligible. However, several case reports of
      interactions with warfarin have been published, including one involving severe
      bleeding. Patients on vitamin K antagonists must be warned about this risk of
      interactions so that they avoid consuming cranberry-based products without
      medical supervision.

PMID- 16989033
TI  - Does sex education affect adolescent sexual behaviors and health?
AB  - This study examines whether offering sex education to young teenagers affects
      several measures of adolescent sexual behavior and health: virginity status,
      contraceptive use, frequency of intercourse, likelihood of pregnancy, and
      probability of contracting a sexually transmitted disease. Using data from the
      National Longitudinal Study of Adolescent Health, I find that while sex education
      is associated with adverse health outcomes, there is little evidence of a causal
      link after controlling for unobserved heterogeneity via fixed effects and
      instrumental variables. These findings suggest that those on each side of the
      ideological debate over sex education are, in a sense, both correct and mistaken.
      Opponents are correct in observing that sex education is associated with adverse
      health outcomes, but are generally incorrect in interpreting this relationship
      causally. Proponents are generally correct in claiming that sex education does
      not encourage risky sexual activity, but are incorrect in asserting that
      investments in typical school-based sex education programs produce measurable
      health benefits.

PMID- 16989034
TI  - Does early adolescent sex cause depressive symptoms?
AB  - A recent study by the Heritage Foundation (Rector, Johnson, & Noyes, 2003) found
      evidence of a positive relationship between early sexual intercourse and
      depressive symptoms. This finding has been used to bolster support for funding
      abstinence only sex education. However, promoting abstinence will only yield
      mental health benefits if there is a causal link between sexual intercourse and
      depression. Using the National Longitudinal Study of Adolescent Health (Add
      Health), I carefully examine the relationship between early teen sex and several
      measures of depression. Controlling for a wide set of individual level and family
      level observable characteristics, cross section estimates consistently show a
      significant positive relationship between early sexual activity for females and
      three measures of adverse mental health: self reported depression, a belief that
      one's life is not worth living, and serious thoughts of suicide. However,
      difference-in-difference estimates reflect no evidence of a significant
      relationship between early teen sex and depressive symptoms. These findings
      suggest that the positive association observed by Rector et al. (2003) can be
      explained by unmeasured heterogeneity. Thus, promoting abstinence among
      adolescents is unlikely to alleviate depressive symptoms

PMID- 16989035
TI  - Obesity, food marketing and consumer litigation: threat or opportunity?

PMID- 16989036
TI  - Not the next tobacco: defenses to obesity claims.

PMID- 16989037
TI  - Defending an emerging threat: consumer fraud class action suits in pharmaceutical
      and medical device products-based litigation.

PMID- 16989038
TI  - Consumer litigation and FDA-regulated products: the unique state of California.

PMID- 16989039
TI  - The Class Action Fairness Act of 2005: changing the class action landscape
      circuit by circuit.

PMID- 16989040
TI  - The Canadian perspective: trends in drug and medical device class actions in
      Canada.

PMID- 16989041
TI  - Pros and cons of off-label promotion investigations and prosecutions.

PMID- 16989042
TI  - Valuable lessons from research on drugs for adolescent obesity in Mexico.

PMID- 16989043
TI  - Angiotensin-converting enzyme inhibitors found unsafe at any time during
      pregnancy.

PMID- 16989044
TI  - Suboptimal reporting of notifiable diseases in Canadian emergency departments: a
      survey of emergency physician knowledge, practices, and perceived barriers.

PMID- 16989045
TI  - Short-term treatment of sleep apnea with nocturnal continuous positive airway
      pressure does not improve blood pressure in patients with well controlled
      hypertension.

PMID- 16989046
TI  - Laboratory-confirmed influenza-associated hospitalizations among children in the
      metropolitan Toronto and Peel region by active surveillance, 2004-2005.

PMID- 16989047
TI  - [Lev L'vovich Kiselev].

PMID- 16989048
TI  - [Special issue: RNA-protein interactions. Dedicated to Lev L'vovich Kiselev (on
      his 70th birthday)].

PMID- 16989049
TI  - [Ongoing care in primary care teams: a subject still to be dealt with].

PMID- 16989050
TI  - [Teaching at the pre-grade of primary health care/family medicine].

PMID- 16989051
TI  - [Social support and primary health care].

PMID- 16989052
TI  - [Diagnosis of the health of a diabetic population in the county of Priorato in
      Tarragona province].
AB  - A health diagnosis made over a two-year period in the basic health area of Falset
      is described (17 municipalities with populations between 39 and 2,603
      inhabitants, making-up a total reference population of 7,283 habitants) in
      relation to the diabetic population of the Priorato county in Catalunya. This
      county is geographically heterogeneous, with semi-arid hilly landscape, with poor
      communications, a farming population and a notoriously hostile climate. The
      population pyramid, inclined towards progressive aging of the population, is
      evidence of a major migration from the country. By means of continuous education
      of health personnel, updating of information sources, improvement of registration
      systems, and final evaluation, the outlines of an action plan is worked out with
      a view to the organisation of diabetic care in this rural context. A total of 226
      diabetics were counted: 15 type 1 (6.2%), and 211 type II (93.8%). The incidence
      of diagnosed diabetes in the basic health area is 3.1% (1.4% to 10.33%). The
      average age of the patients was 65.6 years with a preponderance of women (146 =
      64.6%). In 92 patients (40.2%) the evolution time was less than 5 years. The
      insulinisation rate was calculated at 26.1%. The typical diabetic patient is a
      retired person or a housewife (87.8), with primary of elementary education
      (82.7%), supported by the family.

PMID- 16989053
TI  - [A comparison between three questionnaires and laboratory tests for the detection
      of alcoholism in general practice].
AB  - By means of a case/control study, an attempt was made to identify the different
      questionnaires and biological tests which might be used in the General Practice
      consulting room for the detection of alcoholic patients. A comparison was made
      between the CABE, MALT, and Skinner questionnaires, and the MCV, AST, ALT, GGT
      triglyceride, cholesterol, uric acid, bilirubin and glycemia biological tests.
      Sensitivity, specificity, predictive value and diagnostic efficiency were studied
      in a group of 37 confirmed alcoholics and 25 controls making up a population with
      a high prevalence of alcoholism. Later we analysed the changes which affect the
      values of the different tests when applied to a population with a low prevalence
      of alcoholism, in other words, the utility of the tests in general practice was
      evaluated. The study concludes that the diagnostic performance of the
      questionnaires together with case history is higher than that of biological tests
      in general practice, and that the routine application tests in general practice,
      and that the routine application of the CAGE questionnaire and to a lesser extent
      of the Skinner questionnaire make it possible to identify those patients
      suspected of alcoholism and to improve the predictive value of the biological
      tests applied thereafter. Nevertheless further study is necessary to confirm the
      diagnostic effectiveness of these questionnaires in the general population of
      health centre patients.

PMID- 16989054
TI  - [Evaluation of the pregnancy control programme in the La Chana Health Centre in
      1989. A comparison with previous years].
AB  - OBJECTIVE: An evaluation of the programme with respect to the objective set for
      the year 1989 and a comparison with the evaluation results from previous years.
      DESIGN: It is a retrospective diachronic study, by observation. LOCATION: The
      study was carried out in the primary health area in the basic health zone of La
      Chana in the Granada North health district. PATIENTS: All pregnancies attended in
      the basic health zone during 1989. FIGURES AND PRINCIPAL RESULTS: 223 women
      reached the end of the pregnancy in 1989 of whom 207 joined the programme. The
      level of puerperal visits (83.5% of the pregnancies) and the coverage of the
      programme (59.4%) were below target. Other indicators were above target. The
      average number of visits per pregnancy has reduced over the years (5.5 in 1987;
      4.5 in 1988; 4.4 in 1989), while the percentage for risk levels has been
      maintained. CONCLUSIONS: The programme seems valid but could be improved,
      particularly where coverage is concerned. Analysis and comparison of results with
      previous years highlights the lack of coordination existing between the different
      levels of attendance. Finally we have to point out that we are unaware of the
      quality of attention which is received, and this aspect should receive serious
      study.

PMID- 16989055
TI  - [Validation of a functional social support scale for use in the family doctor's
      office].
AB  - OBJECTIVE: The present work seeks to validate the Duke-UNC questionnaire as
      modified by Broadhead, which is used to measure social support in its qualitative
      dimension. DESIGN: It is a transversal, prospective and observational study.
      LOCATION: The study has been done at the primary care level, corresponding to the
      basic health area of Cartuja (Granada). PATIENTS: The questionnaire was
      administered to 139 patients seen in the offices of the Cartuja Health Centre. 25
      of them were male and 114 female, of an age ranging from 18 to 84. The subjects
      were selected on a systematic base of three by three with a random starting-point
      from among people over 18 years old visiting the office. INTERVENTIONS: To check
      the reliability and validity of the questionnaire, Pearson's, Edward's and
      Cronbach's alpha techniques were used. The factorial analysis was verified by the
      varimax rotation method. MEASUREMENTS AND MAIN RESULTS: We have observed that the
      questionnaire correctly measures qualitative social support, it being appreciated
      that the correlation coefficients are high, as is the internal consistency of the
      scale. After the factorial analysis we also confirmed the existence of two
      components: Factor 1 which measures the confidential social support and Factor 2
      which measures the affective social support. CONCLUSIONS: The Duke-UNC
      questionnaire reduced to 11 items is a fast and simple instrument for detecting
      the level of social support in its affective and confidential dimensions. Its use
      will allow us to discover situations of high social risk; permitting us in these
      cases to carry out the relevant support interventions.

PMID- 16989057
TI  - [Viral hepatitis].

PMID- 16989056
TI  - [Central anticholinergic syndrome].
AB  - Two new cases of anticolinergic central syndrome are described. The first case, a
      8 year old girl, suffered a severe encefalopathy after topical application of
      mydriatic cholirio as an aid in a rutine study of ocular refraction. The second
      case, 67 year old man presented a severe neurological picture after accidental
      intake of a silvester plantground (Atropa belladonna). His neurological condition
      returned quickly to normal whith administration of physostigmine. Differents
      aspects of the etiology, clinical picture and diagnosis are discussed with
      special emphasis in patients with delirium or acute confusional states. Finally,
      attention is drawn in the necessity of a properly use of anticholinergic drugs
      overcoat in aged or children.

PMID- 16989058
TI  - [Ultrasonography in pediatrics].

PMID- 16989059
TI  - [Primary care oriented to the community (and II)].

PMID- 16989060
TI  - [Four cases of parotiditis in vaccinated children].

PMID- 16989061
TI  - [Opinions of diabetic patients on their sanitary education].

PMID- 16989062
TI  - [Descriptive study of emergencies in the Icod de los Vinos (Tenerife) health
      care].

PMID- 16989063
TI  - [Importance of health education: reflections arising from "a spoon"].

PMID- 16989064
TI  - [Glycyrrhiza glabra and other herbs].

PMID- 16989065
TI  - Effects of angiotensin-converting enzyme inhibitors in experimental diabetes.
AB  - Clinical and experimental diabetic states are often characterized by an increase
      in the glomerular filtration rate, and early hyperfiltration may be a risk factor
      for the later development of diabetic glomerulopathy. Evidence in diabetic animal
      models suggests that, of the determinants of diabetic hyperfiltration, glomerular
      capillary hypertension plays a key role in the development of structural injury.
      In diabetic rats, despite normal systemic blood pressure, the glomerular
      capillary pressure is elevated because of disproportionate vasodilation of the
      afferent arteriole. In this normotensive model, a modest reduction in systemic
      blood pressure with angiotensin I-converting enzyme inhibitor therapy normalizes
      glomerular capillary pressure and retards the development of injury. However,
      animal studies suggest that all antihypertensive regimens may not afford
      equivalent protection. It has been reported that monotherapy with calcium channel
      blockers, or hydralazine, is less effective in limiting albuminuria than are
      angiotensin-converting enzyme inhibitors. In a study comparing the effects of
      angiotensin-converting enzyme inhibitors with those of reserpine,
      hydrochlorothiazide, and hydralazine, both regimens lowered blood pressure and
      offered some long-term protection. However, angiotensin-converting enzyme
      inhibition resulted in significantly greater limitation of injury than did the
      combination regimen. These results suggest that antihypertensive therapy retards
      diabetic renal disease; however, some anti-hypertensive regimens may afford
      superior protection.

PMID- 16989066
TI  - Renal hemodynamics and permselectivity.
AB  - Glomerular capillary hemodynamics influence glomerular permselectivity to
      macromolecules, and alterations in these factors can evoke proteinuria. Changes
      in hemodynamic patterns can alter protein flux by changing its diffusion- or
      concentration-driven movement in the presence of a constant membrane barrier.
      Alternatively, hemodynamic forces may disrupt, transiently or irreversibly, the
      permeability characteristics of the capillary barrier. Maneuvers that lower
      glomerular capillary pressure appear capable of reversing, at least in part,
      these latter permeability defects. Angiotensin II, provoked by higher levels of
      dietary protein intake, may be a particularly important mediator of proteinuria,
      both through its effects on diffusion-mediated protein leakage and its tendency
      to provoke permeability defects due to the heightening of glomerular capillary
      hydraulic pressures.

PMID- 16989067
TI  - Angiotensin-converting enzyme inhibitors in diabetes: effect on the kidney and on
      blood pressure.
AB  - In diabetes mellitus, studies on the renin angiotensin system conflict. Among
      type I diabetic patients, we have found normal plasma renin activity and
      angiotensin II levels. In these patients, low-dose angiotensin II infusion
      resulted in the same effect on renal hemodynamics as that observed in healthy
      controls. In patients with diabetic nephropathy, a disease usually regarded as a
      low-renin condition, we have found elevated levels of plasma renin activity as
      compared with that seen in healthy persons and control subjects with other renal
      diseases that result in a similar degree of renal failure. In patients with
      diabetic nephropathy, interruption of the renin angiotensin system with
      angiotensin-converting enzyme inhibitors has been associated with a reduction in
      proteinuria. It is not clear whether this is a result of blood pressure reduction
      or a specific effect of these drugs. In a randomized trial with patients with
      diabetic nephropathy, we found that enalapril treatment reduced proteinuria to
      less than half the level obtained in a metoprolol-treated group during equally
      effective blood pressure control. In a long-term prospective study of captopril
      in patients with diabetic nephropathy, the rate of decline in kidney function was
      reduced to half the value that was calculated during a retrospective period. The
      renin angiotensin system, therefore, can be normally active in patients with
      diabetic nephropathy, and angiotensin-converting enzyme inhibitors can reduce
      proteinuria by mechanisms independent of their effect on blood pressure. Long
      term treatment may protect renal function to a greater degree than might be
      expected from the blood pressure-lowering effect.

PMID- 16989068
TI  - Converting enzyme inhibition and glomerular size selectivity in diabetic
      nephropathy.
AB  - Differential solute clearances were used to examine the effects of enalapril on
      glomerular barrier function in 16 proteinuria patients with diabetic
      glomerulopathy. In these patients, a 90-day course of enalapril reduced arterial
      pressure without lowering renal plasma flow or glomerular filtration rate.
      Glomerular clearances of dextrans of broad size distribution (28 to 60 A) were
      lowered significantly. Theoretical analysis of the dextran clearance profiles
      revealed that enalapril shifted glomerular pore size distribution to a smaller
      size. This change in barrier size selectivity was associated with a reduction in
      fractional albumin and immunoglobulin G clearances during enalapril therapy;
      urinary protein excretion tended to decrease in parallel. These results indicate
      that converting enzyme inhibition diminishes glomerular permeability to proteins
      in diabetic nephropathy by enhancing barrier size selectivity. Because enalapril
      therapy did not alter the renal plasma flow rate or glomerular filtration rate,
      these results further suggest that the primary action of enalapril may be to
      modulate the intrinsic membrane properties of the glomerular barrier.

PMID- 16989069
TI  - Lipids and the progression of renal disease.
AB  - The mechanisms involved in progressive renal injury have been the subject of
      intense investigation during the past decade. Hemodynamic and nonhemodynamic
      factors have been implicated in progressive renal damage, including abnormalities
      of lipid metabolism. The idea that abnormal lipid metabolism may be important in
      the development and progression of renal injury has intrigued investigators for
      over 100 years. Studies in models of progressive renal insufficiency have
      demonstrated that abnormalities in lipid metabolism may participate in the
      development of glomerular and tubular alterations leading to nephron destruction.
      This concept has been supported by the demonstration that pharmacologic
      intervention with different classes of lipid-lowering agents is associated with a
      reduction in the extent and severity of glomerular and tubular injury. The
      mechanism whereby hyperlipidemia contributes to renal injury are at present
      unknown. Morphologically, marked expansion of the mesangial matrix, prior to the
      development of glomerulosclerosis, suggests the possibility that altered
      production of mesangial matrix proteins may contribute to glomerular injury.
      Increased numbers of glomerular monocyte-derived macrophages and foam cells in
      hyperlipidemic rats have been described. The role that these cells may play in
      the development of proteinuria and glomerular damage has not been clarified.
      Biochemically, increased renal tissue content of cholesterol esters and reduced
      concentrations of essential fatty acids have been described. Whether these
      changes in tissue lipids contribute to renal injury is also unknown. In addition,
      persistent hyperlipidemia, particularly hypercholesterolemia, may also lead to
      glomerular hypertension, possibly through alterations in eicosanoid metabolism.
      Finally, preliminary data have suggested that oxidized lipoproteins may
      contribute to the hemodynamic and structural changes described in lipid-induced
      renal injury. The roles of altered platelet function and other lipid-derived
      inflammatory mediators are yet to be explored. In conclusion, experimental
      studies have indicated that hyperlipidemia is an important modulator of nephron
      damage and may contribute to the progression of renal disease. Whether
      alterations in lipid metabolism participate in progressive renal insufficiency in
      humans remains to be determined.

PMID- 16989070
TI  - Reduction in proteinuria attenuates hyperlipidemia in the nephrotic syndrome.
AB  - Hyperlipidemia in the nephrotic syndrome is characterized by increased synthesis
      of lipids as well as reduced removal of lipids from the blood. When rats with
      nephrotic syndrome are fed a 40% protein diet, urinary albumin excretion and rate
      of albumin synthesis increase. Serum cholesterol and triglyceride concentration
      increase as well. If the increase in albuminuria, but not the increase in the
      rate of albumin synthesis resulting from dietary protein augmentation, is
      prevented by the administration of enalapril, serum triglyceride and cholesterol
      concentration are not increased but are reduced nearly to within the normal
      range. Proteinuria, and not an increased rate of albumin synthesis, thus plays a
      causal role in nephrotic hyperlipidemia. Therapy directed at correcting altered
      glomerular permselectivity, while perserving an increased rate of albumin
      synthesis, may be effective in managing nephrotic hyperlipidemia.

PMID- 16989071
TI  - Renal protection in essential hypertension: how do angiotensin-converting enzyme
      inhibitors compare with calcium antagonists?
AB  - By interrupting the integrity of the systemic and renal renin-angiotensin system,
      angiotensin-converting enzyme inhibitors have been shown, experimentally, to
      preferentially reduce postglomerular capillary arteriolar resistance, to reduce
      glomerular capillary pressure, and to increase the ultrafiltration coefficient.
      Under normal physiological conditions, angiotensin-converting enzyme inhibitors
      have little effect on glomerular filtration rate; however, they increase
      effective renal plasma flow at renal perfusion pressures within the normal
      autoregulatory range and renal vascular resistance is decreased. In contrast,
      calcium antagonists have been shown, experimentally, to preferentially reduce
      preglomerular capillary arteriolar resistance. Their effects on angiotensin II
      and postglomerular capillary arteriolar resistance (hence, glomerular capillary
      pressure and the ultrafiltration coefficient) are controversial. Under normal
      physiological conditions, calcium antagonists increase both glomerular filtration
      rate and effective renal plasma flow at renal perfusion pressures within the
      normal autoregulatory range and renal vascular resistance is decreased. In
      patients with essential hypertension, studies have demonstrated that angiotensin
      converting enzyme inhibitors (as predicted) sustain glomerular filtration rate,
      increase effective renal plasma flow, and decrease renal vascular resistance.
      However, essential hypertensive patients with impaired glomerular filtration rate
      may demonstrate marked improvement in both glomerular filtration rate and
      effective renal plasma flow. Calcium antagonists (as predicted) may increase both
      glomerular filtration rate and effective renal plasma flow (at high renal
      perfusion pressures) and may decrease renal vascular resistance. Calcium
      antagonists may also improve both glomerular filtration rate and effective renal
      plasma flow in patients with impaired glomerular filtration rate. Long-term
      clinical trials comparing the renal effects of angiotensin-converting enzyme
      inhibitors with those of calcium antagonists in essential hypertensive patients
      have not been reported. It remains to be determined if the potentially different
      effects of these two classes of antihypertensive drugs on the renal
      microcirculation do or do not translate into different renal protective
      advantages to patients at risk for the development and/or progression of
      hypertensive nephrosclerosis.

PMID- 16989072
TI  - Renal microvascular actions of calcium antagonists.
AB  - Calcium antagonists elicit vasodilation by altering the function of a specific
      class of potential-dependent calcium channels. These agents alter renal
      hemodynamics in a complex manner. Studies in the isolated perfused rat kidney
      demonstrate that the renal vasodilatory response to calcium antagonists varies
      depending on the nature of the underlying renal vasoconstriction. Thus, not all
      renal vasoconstrictor mechanisms are sensitive to calcium antagonists.
      Furthermore, in the presence of agonists such as norepinephrine or angiotensin
      II, calcium antagonists exert a greater effect on glomerular filtration rate than
      on renal perfusate flow. Direct observations of the renal microvasculature
      suggest that this preferential augmentation of glomerular filtration rate
      reflects the ability of calcium antagonists to dilate preglomerular vessels while
      preserving efferent arteriolar tone. Thus, under identical in vitro conditions,
      calcium antagonists reverse afferent (preglomerular) but not efferent
      (postglomerular) arteriolar vasoconstriction in isolated perfused hydronephrotic
      kidneys. Similarly, potassium (KCl)-induced depolarization, which directly
      activates potential-dependent calcium channels, preferentially constricts the
      afferent arteriole and produces a striking decrease in glomerular filtration rate
      and filtration fraction. Such observations indicate that differing activating
      mechanisms mediate vasoconstriction within the renal microcirculation and suggest
      that potential-dependent calcium channels prominently contribute to afferent, but
      not efferent, arteriolar vasoconstriction.

PMID- 16989073
TI  - Interactions of the endothelium and mesangium in glomerular injury.
AB  - Glomerular mesangial and endothelial cells have key roles in the regulation of
      glomerular blood flow, both under normal circumstances and in pathologic states.
      The anatomic structure of the glomerulus is such that the endothelial and
      mesangial cells are in close proximity to each other and consequently may
      communicate through a number of cellular mediators. Vasodilatory substances, such
      as prostacyclin and endothelium-derived relaxing factor, and vasoconstrictive
      substances, such as endothelin, are released by endothelial cells and can
      interact with mesangial cells to affect glomerular blood flow. The ability of
      plasma macromolecules to enter and circulate through the mesangium may play an
      important role in the development of glomerular injury. Angiotensin II has been
      shown to increase the uptake and decrease the rate of disappearance of certain
      macromolecules in the mesangium; this action is blocked, at least partially, by
      angiotensin II receptor antagonists and by calcium channel blockers. Experimental
      studies have suggested that angiotensin converting enzyme inhibitors and calcium
      channel blockers may prevent or arrest progression of renal injury. Angiotensin
      converting enzyme inhibitors may ave a beneficial effect by decreasing
      intraglomerular pressure through inhibition of angiotensin II predominant
      constriction of the glomerular efferent arteriole and possibly by decreasing
      mesangial trafficking of macromolecules. Calcium channel blockers may have
      beneficial effects on intracellular events that occur because of injury of either
      endothelial or mesangial cells.

PMID- 16989074
TI  - Effects of calcium channel blockers on experimental glomerular injury.
AB  - A major problem for patients with kidney disease is that most chronic renal
      diseases progress to endstage renal failure. Studies in experimental models of
      hypertension and renal insufficiency suggest that progressive glomerular
      sclerosis may be the long-term consequence of functional and structural
      adaptations of the kidney to a moderate loss of filtration capacity. In a number
      of settings, sclerosis has been related to the presence of an elevated glomerular
      capillary hydraulic pressure. A growing body of evidence also supports the
      hypothesis that kidney hypertrophy and glomerular hypertrophy constitute
      independent risk factors for glomerular sclerosis. Recent studies suggest that
      calcium antagonists can reduce glomerular injury in experimental hypertension.
      Renal protection may be related to the ability of these agents to reduce
      glomerular pressure and/or inhibit compensatory renal growth.

PMID- 16989075
TI  - Calcium channel blockers in organ transplantation: important new therapeutic
      modalities.
AB  - The calcium channel blockers have emerged as important therapeutic modalities in
      the treatment of hypertension, ischemic heart disease, and other cardiovascular
      diseases. More recently, their potential benefit in recipients of organ
      transplants has come under closer scrutiny. Calcium channel blockers depress in
      vitro cellular immunity in an additive fashion with cyclosporine and have been
      demonstrated to reduce the incidence of rejection posttransplantation in early
      clinical trials. This class of drugs may also diminish ischemic damage to
      transplanted organs and reduce the destructive aspects of reperfusion injury.
      Because of their ability to depress cellular immune responses to mitogens,
      calcium channel blockers may also prove useful in decreasing the incidence of
      first-dose side effects (related to lymphocyte stimulation) in response to
      treatment with the OKT3 monoclonal antibody, a commonly used antirejection
      medication. Recent investigative efforts also suggest that calcium channel
      blockers may minimize cyclosporine nephrotoxicity by antagonizing either the
      direct or indirect vasoconstrictive actions of the drug. Some of the calcium
      channel blockers also reduce cyclosporine metabolism and excretion, thus allowing
      adequate levels of cyclosporine in blood with reduced doses of this valuable
      immunosuppressive agent. Cyclosporine-treated renal transplant recipients are
      frequently hypertensive, which is likely related to a salt-sensitive physiology.
      Calcium channel blockers have demonstrated important efficacy in reducing blood
      pressure in low-renin, salt-sensitive patients and similarly have been
      efficacious in controlling blood pressure in cyclosporine-treated transplant
      recipients. The numerous potential applications of calcium channel blockers in
      the field of organ transplantation illustrates the need for expanded clinical
      trials evaluating their use in this area.

PMID- 16989076
TI  - Relationship between hypertension and subtle and overt abnormalities of
      carbohydrate metabolism.
AB  - In patients with type II diabetes mellitus, the prevalence of hypertension is
      increased as much as twofold over that in the nondiabetic population.
      Hypertension in diabetic patients increases the risk and accelerates the course
      of development of cardiac disease, stroke, peripheral vascular disease,
      retinopathy, and nephropathy. Despite the importance of hypertension in type II
      diabetics, the basic mechanisms that initiate and sustain hypertension in these
      patients are poorly understood. Contributing factors discussed in this review
      include the following: obesity, insulin resistance, hyperinsulinemia, genetic
      factors, and abnormalities of cellular cation homeostasis. Also discussed are the
      features of hypertension in type II diabetic individuals which are reminiscent of
      the hemodynamic abnormalities characterizing hypertension in the elderly,
      including increased vascular reactivity and increased atherosclerotic vascular
      disease. Recent evidence has shown that insulin resistance and hyperinsulinemia
      exist in as many as 50 to 70% of adult nonobese individuals with untreated
      hypertension. These observations strongly suggest that the disease known as
      hypertension is characterized by fundamental abnormalities of metabolism as well
      as by hemodynamic alterations. This review discusses the mechanisms by which
      hyperinsulinemia and/or insulin resistance may lead to hypertension. Elevated
      levels of triglycerides in plasma and suppressed high-density lipoprotein
      cholesterol concentrations are often observed in hypertensive individuals. These
      elevations may result, in part, from hyperinsulinemia and/or insulin resistance.
      Information will be presented suggesting that subtle abnormalities of
      carbohydrate metabolism that exist in patients with hypertension may contribute
      to the accelerated cardiovascular disease that accompanies the hypertension
      state. This review also addresses both special concerns about metabolic
      consequences of antihypertensive therapy in hypertensive patients with subtle
      carbohydrate intolerance as well as those in hypertensive patients with overt
      diabetes.

PMID- 16989077
TI  - [The authentic knowledge].

PMID- 16989078
TI  - [To innovate the practical nurse; focus based on professional competencies (I)].
AB  - The Nursing practice has entered into a period of rapid, global changes which
      require firm support in order to maximize their role in the health field.
      Together with the transitional situation health systems are undergoing, this
      obliges nurses to search for new innovative methods to comply with their
      professional duties and for the creation of instruments that facilitate the
      increase in the quality treatment nurses provide, as well as the mechanisms
      through which excellence in educational preparation and professional compliance
      are recognized. In the following pages, the authors deal with this focus based on
      professional competencies as a tool which nears these objectives.

PMID- 16989079
TI  - [A critical vision about nursing diagnoses].
AB  - This article is an adaptation of a conference by the author in which she planted
      critical perspectives and questions about nursing diagnoses in order to see these
      from another viewpoint. The author introduces some new considerations related to
      the nursing paradigm which recognize the human nature in the treatment process
      centered on a relationship. This discourse is important from nursing language and
      practice viewpoints since they make evident basic human process in professional,
      ethical and practical treatment.

PMID- 16989080
TI  - [Interrelationship among "NANDA, NOC and NIC". A pilot study and an evaluation of
      a nursing document].
AB  - OBJECTIVES: (a) to determine the effectiveness of a nursing document which
      integrates nursing diagnoses, nursing treatments/actions (NIC), and results
      (NOC); (b) to verify the application of the aforementioned document in a
      hospitalization unit. MATERIALS AND METHODS: A descriptive, transversal and
      observational study. MATERIALS: Nursing documents (NANDA, NIC and NOC
      taxonomies). PHASES: 1st: analysis of the content in the nursing documentation
      for 23 pneumonic patients: Selection of nursing diagnoses and the most frequent
      interdependent problems. 2nd: Selection of results and nursing treatment/actions.
      3rd: Elaboration of the document and a description of the Likert scales to define
      the state of the indicators for each result. 4th: A pilot study of the document
      applied to 12 patients. CONCLUSIONS: the application of the document permits one
      to identify the real status of a patient; to establish specific objectives; to
      improve the recording of data; to observe the effectiveness of treatment; to
      include educational activities; to give greater continuity and quality to a
      treatment plan.

PMID- 16989081
TI  - [Do nurses utilize the scientific method?].
AB  - The authors wanted to discover the utilization of the Process of Nursing
      Attention and the NANDA Diagnoses, as well as the main reasons why these methods
      are or are not put to use. The authors conclude that the non-use of these methods
      is due to their difficult and complicated language.

PMID- 16989082
TI  - [Teaching in Europe].
AB  - The European Area for Higher Education is the venue where, over a medium time
      frame, important changes in the Spanish university system shall be carried out in
      order to achieve the necessary convergence with the rest of the European Union
      countries. The step from an information society to a knowledge-based society will
      require a change in the pedagogical process and the curricula in all university
      disciplines and their subsequent adaptation to the new plans formulated by the
      European Area for Higher Education. Therefore, nursing faces a new challenge
      which will allow it to develop its full academic potential under conditions equal
      to those of all other academic disciplines.

PMID- 16989083
TI  - [A return to reason. The problematic of the construction of knowing how to
      discipline by means of nursing diagnoses].
AB  - This article is adapted from a conference paper in which some ideas were
      transmitted which will be made concrete in a problematic analysis on nursing
      diagnoses. This takes place upon perceiving the necessity in the process of
      professional development and nursing discipline, to shed some light and
      comprehend what other viewpoints bring to the understanding of assistance,
      teaching and investigative practices. Today more than ever it has become
      necessary to recuperate a problematic and critical thinking which permits us to
      go beyond that which has been presented to us as licit and true knowledge as "the
      only thought" on occasions. One perceives certain stiffness in the habitual forms
      of thinking about treatment (the objective of Nursing as a discipline) and an
      ostensible "loss of sense" in practice; and this crisis threatens a rigorous exam
      and a questioning of the traditional forms of thinking, describing, teaching and
      exercising treatment practice. This is the pretense of the following essay.

PMID- 16989084
TI  - Applications of combined spectral lifetime microscopy for biology.
AB  - Live cell imaging has been greatly advanced by the recent development of new
      fluorescence microscopy-based methods such as multiphoton laser-scanning
      microscopy, which can noninvasively image deep into live specimens and generate
      images of extrinsic and intrinsic signals. Of recent interest has been the
      development of techniques that can harness properties of fluorescence, other than
      intensity, such as the emission spectrum and excited state lifetime of a
      fluorophore. Spectra can be used to discriminate between fluorophores, and
      lifetime can be used to report on the microenvironment of fluorophores. We
      describe a novel technique-combined spectral and lifetime imaging-which combines
      the benefits of multiphoton microscopy, spectral discrimination, and lifetime
      analysis and allows for the simultaneous collection of all three dimensions of
      data along with spatial and temporal information.

PMID- 16989085
TI  - Gentamicin and other cassettes for chromosomal gene replacement in Escherichia
      coli.

PMID- 16989086
TI  - Construction of eukaryotic surface display based on the baculoviral F protein.

PMID- 16989087
TI  - Reversal of PCR bias for improved sensitivity of the DNA methylation melting
      curve assay.

PMID- 16989088
TI  - Translational efficiency of EMCV IRES in bicistronic vectors is dependent upon
      IRES sequence and gene location.
AB  - The internal ribosomal entry site (IRES)from encephalomyocarditis virus (EMCV) is
      a popular RNA element used widely in experimental and pharmaceutical applications
      to express proteins in eukaryotic cells or cell-free extracts. Inclusion of the
      wild-type element in monocistronic or bicistronic messenger RNAs (mRNAs) confers
      a high level of cap-independent translation activity to appropriately configured
      cistrons. The history of this element and the experimental consequences of
      sequence derivations inherent to commercial IRES vectors are less well known.
      Compared head-to-head with dual-luciferase reporter constructs, a native EMCV
      IRES in a bicistronic configuration directed 8- to 10-fold more protein than a
      similarly configured pIRES vector. It also produced nearly twice as much protein
      as pCITE-1, an early monocistronic iteration, harboring a suboptimal A7 sequence
      in a crucial structural motif The results indicate that investigators should be
      aware of and carefully report the sequence of their IRES in any comparative
      study. The preferred IRES (viral bases 273-845) and the minimum IRES (viral bases
      400-836) for optimum activity are illustrated.

PMID- 16989089
TI  - Wet electron microscopy with quantum dots.
AB  - Wet electron microscopy (EM) is a new imaging method with the potential to allow
      higher spatial resolution of samples. In contrast to most EM methods, it requires
      little time to perform and does not require complicated equipment or difficult
      steps. We used this method on a common murine macrophage cell line, IC-21, in
      combination with various stains and preparations, to collect high resolution
      images of the actin cytoskeleton. Most importantly, we demonstrated the use of
      quantum dots in conjunction with this technique to perform light/electron
      correlation microscopy. We found that wet EM is a useful tool that fits into a
      niche between the simplicity of light microscopy and the high spatial resolution
      of EM.

PMID- 16989090
TI  - Scintillation proximity assay for DNA binding by human p53.
AB  - Many DNA binding proteins are known to regulate gene expression. When that
      binding is altered, a disease state can result. A common method for measuring DNA
      binding, namely electrophoretic mobility shift assay (EMSA) is often used but it
      is not amenable to rapid screening of many samples. As an alternative method, we
      have developed a DNA binding assay for the tumor suppressor protein p53 in a 96
      well microtiter plate format using scintillation proximity assay (SPA) beads. We
      have shown this assay to be sensitive (as little as 0.5 ng p53 can be detected),
      quick (assay completed in as little as 15 min), and easily quantitated using a
      microtiter plate scintillation counter We also used the assay to analyze the
      kinetics of the DNA binding to p53. The specificity of this p53 DNA binding SPA
      was confirmed using competition by oligonucleotides either from the same gene or
      from mutated versions of this sequence. Thus, SPA is a good alternative to gel
      shift assays for DNA binding and may be useful for the analysis of multiple tumor
      cell samples or for high-throughput screens for compounds affecting DNA binding
      by proteins of interest.

PMID- 16989091
TI  - Simple one-week method to construct gene-targeting vectors: application to
      production of human knockout cell lines.
AB  - Targeted gene disruption is a powerful tool for studying gene function in cells
      and animals. In addition, this technology includes a potential to correct disease
      causing mutations. However, constructing targeting vectors is a laborious step in
      the gene-targeting strategy, even apart from the low efficiency of homologous
      recombination in mammals. Here, we introduce a quick and simplified method to
      construct targeting vectors. This method is based on the commercially available
      MultiSite Gateway technology. The sole critical step is to design primers to PCR
      amplify genomic fragments for homologous DNA arms, after which neither ligation
      reaction nor extensive restriction mapping is necessary at all. The method
      therefore is readily applicable to embryonic stem (ES) cell studies as well as
      all organisms whose genome has been sequenced. Recently, we and others have shown
      that the human pre-B cell line Nalm-6 allows for high-efficiency gene targeting.
      The combination of the simplified vector construction system and the high
      efficiency gene targeting in the Nalm-6 cell line has enabled rapid disruption of
      virtually any locus of the human genome within one month, and homozygous knockout
      clones lacking a human gene of interest can be created within 2-3 months. Thus,
      our system greatly facilitates reverse genetic studies of mammalian--particularly
      human--genes.

PMID- 16989092
TI  - Heat-inducible autolytic vector for high-throughput screening.
AB  - In directed evolution, a high-throughput screening system is often a prerequisite
      for sampling the enzyme variants. When the target enzyme is expressed
      intracellularly, for example when Escherichia coli is used as the host, chemical
      or enzymatic disruption of cell membrane is often required in many cases, which
      can be tedious, time-consuming, and costly. In this study, a set of heat
      inducible autolytic vectors were constructed to solve this problem, in which the
      SRRz lysis gene cassette from bacteriophage lambda was placed downstream of heat
      inducible promoters, lambda cI857/pR promoter and its mutant, c1857/pR(M). The
      artificial autolytic units were inserted into the backbone of pUC18 (away from
      the multiple cloning sites). For the wild promoter; cI857/pR, the SRRz lysis
      cassette was expressed by temperature up-shift from 28 degrees to 38 degrees C,
      and the lysis efficiency of transformed bacterial cells was found to be
      consistent and could reach 96.3% as measured by the reporter beta3-galactosidase
      assay. In order to obtain a higher cell growth rate, the mutant promoter
      cI857/pR(M) was utilized to allow bacteria growth at 35 degrees C and lysis at 42
      degrees C. However; this heat-inducible system showed significant inconsistency
      in terms of lysis efficiency. Bacillus subtilis 168 lipase A gene was further
      inserted into the multiple cloning sites of the autolytic vector containing
      cI857/pR, and 93.7% of the expressed lipase activity was found in the culture
      medium upon heat induction, demonstrating the utility of the vector for
      expression and rapid extracellular assay of heterologous enzymes.

PMID- 16989093
TI  - Lectin-based affinity tag for one-step protein purification.
AB  - The production of pure protein is indispensable for many applications in life
      sciences, however protein purification protocols are difficult to establish, and
      the experimental procedures are usually tedious and time-consuming. Therefore, a
      number of tags were developed to which proteins of interest can be fused and
      subsequently purified by affinity chromatography. We report here on a novel
      lectin-based affinity tag using the D-mannose-specific lectin LecB from
      Pseudomonas aeruginosa. A fusion protein was constructed consisting of yellow
      fluorescent protein and LecB separated by an enterokinase cleavage site. This
      protein was overexpressed in Escherichia coli Tuner (DE3), and the cell extract
      was loaded onto a column containing a mannose agarose matrix. Electrophoretically
      pure fusion protein at a yield of 24 mg/L culture was eluted with a D-mannose
      containing buffer The determination of equilibrium adsorption isotherms revealed
      an association constant of the lectin to the mannose agarose matrix of Ka = 3.26
      x 10(5)/M. Enterokinase treatment of the purified fusion protein resulted in the
      complete removal of the LecB-tag. In conclusion, our results indicate that the
      lectin LecB of P. aeruginosa can be used as a tag for the high-yield one-step
      purification of recombinant proteins.

PMID- 16989095
TI  - Nursing leadership: a sustainable future.

PMID- 16989094
TI  - Enrichment of open reading frames presented on bacteriophage M13 using
      hyperphage.
AB  - The enrichment of open reading frames (ORFs) from large gene libraries and the
      presentation of the corresponding polypeptides on filamentous phage M13 (phage
      display) is frequently used to identify binding partners of unknown ORFs. In
      particular phage display is a valuable tool for the identification of pathogen
      related antigens and a first step for the development of new diagnostics and
      therapeutics. Here, we introduce a significant improvement of phage-based ORF
      enrichment by using Hyperphage, a helperphage with a truncated gIII. The methods
      allow both the enrichment of ORFs from cDNA libraries and the display of the
      corresponding polypeptides on phage, thus combining ORF enrichment with a
      screening for binding in one step without any further subcloning steps. We
      demonstrated the benefits of the method by isolating the sequences encoding two
      predicted immunogenic epitopes of the outer membrane protein D encoding gene
      (ompD) of Salmonella typhimurium. Here, we showed that when using a mixture of
      three constructs with only one containing an ORF solely this correct construct
      could be reisolated in phage particles. Further; both epitopes were detected by
      enzyme-linked immunosorbent assay (ELISA), demonstrating correct translation of
      fusion proteins. Furthermore, the enrichment system was evaluated by the
      enrichment of ORFs from total cDNA of lymphocytes. Here, we could show that 60%
      of the phage contained ORFs, which is an increase of an order of magnitude
      compared with conventional phage expression system. Together these data show that
      the Hyperphage-based enrichment system significantly improves the enrichment of
      ORFs and directly allows the display of the corresponding polypeptide on
      bacteriophage M13.

PMID- 16989096
TI  - Autonomic dysreflexia and telehealth.
AB  - With the rapid expansion of telehealth lines in the United States and the
      establishment of provincially funded lines in Canada, a growing number of people
      use this convenient approach to establish their initial health needs and to
      pursue self-care. Telehealth providers, for the most part, rely on electronic
      protocols to offer triaging and advice. Unfortunately, standard protocols are
      misleading when a premorbid health condition such as a spinal cord injury is
      present. Symptoms such as a headache, diaphoresis or an elevated blood pressure,
      which are common occurrences in the general population, may indicate an emergency
      situation, namely autonomic dysreflexia (AD), when a mid-thoracic and higher
      spinal cord lesion is present. Since there is no available electronic protocol on
      AD, this emergency health condition is not recognized by the telehealth provider
      and may put the caller at risk of serious morbidity or even death. In this
      article, the authors present the clinical features of AD, the precipitating
      factors and the nursing management of an episode. The merits and pitfalls of
      electronic protocols are reviewed and an algorithm is presented to assist
      telehealth providers in recognizing AD.

PMID- 16989097
TI  - Advanced practice: A clinical or political issue?
AB  - Advanced practice is characterized by a greater degree of clinical competence,
      critical thinking and professional accountability in the areas of organizational
      management, decision-making and leadership. Advanced practice is praised in
      clinical and academic settings for its beneficial effects on peoples' health.
      However, the authors believe that advanced practice also confers specific
      (corporate) benefits, particularly with respect to acquisition of authority,
      credibility and legitimacy compared to, and in the eyes of, other health
      professionals. This article takes a critical look at the specialization phenomena
      in nursing and encourages dialogue on underlying motivations and the quest for
      professional status

PMID- 16989098
TI  - Access to confidential sexual health services.
AB  - The authors conducted one-on-one interviews with adolescent females, aged 13 to
      16, concerning their perception of the confidentiality of sexual health services
      available to them. Participants were selected from an urban school with a youth
      health centre (YHC) and also from a rural school without access to a YHC. They
      typically viewed traditional health services as not confidential and reported
      concern about disclosure to parents. This qualitative study suggests that
      adolescent females have an absolute need to maintain positive parental regard by
      preventing disclosure of sexual activity.

PMID- 16989099
TI  - A passion for research.

PMID- 16989100
TI  - Dr. orders nurses to follow his protocols--not hospital's.

PMID- 16989101
TI  - Is manufacturer's insert admissible in your state?

PMID- 16989102
TI  - TN: Are agency RNs employees or contractors?: Eligibility for unemployment
      compensation issue.

PMID- 16989103
TI  - Did CRNA get off the hook in this case?

PMID- 16989104
TI  - Mental health care and the workplace.

PMID- 16989105
TI  - Common mental disorders in the workforce: recent findings from descriptive and
      social epidemiology.
AB  - OBJECTIVE: To review the recent descriptive and social epidemiology of common
      mental disorders in the workplace, including prevalence, participation, work
      disability, and impact of quality of work, as well as to discuss the implications
      for identifying targets for clinical and preventive interventions. METHOD: We
      conducted a structured review of epidemiologic studies in community settings
      (that is, in the general population or in workplaces). Evidence was restricted to
      the peer-reviewed, published, English-language literature up to the end of June
      2005. We further restricted evidence to studies that used recent classification
      systems; then, if evidence was insufficient, we reviewed studies that used
      standardized psychiatric screening scales. To distinguish this article from
      recent reviews of health and work quality, we focused on new areas of
      investigation and new evidence for established areas of investigation:
      underemployment, organizational justice, job control and demand, effort-reward
      imbalance, and atypical (nonpermanent) employment. RESULTS: Depression and simple
      phobia were found to be the most prevalent disorders in the working population.
      The limited data on rates of participation suggested higher participation among
      people with depression, simple phobia, social phobia, and generalized anxiety
      disorder. Depression and anxiety were more consistently associated with
      "presenteeism" (that is, lost productivity while at work) than with absenteeism,
      whether this was measured by cutback days or by direct questionnaires. Seven
      longitudinal studies, with an average sample size of 6264, showed a strong
      association between aspects of low job quality and incident depression and
      anxiety. There was some evidence that atypical work was associated with poorer
      mental health, although the findings for fixed-term work were mixed. CONCLUSIONS:
      Mental health risk reduction in the workplace is an important complement to
      clinical interventions for reducing the current and future burden of depression
      and anxiety in the workplace.

PMID- 16989106
TI  - Managing depression-related occupational disability: a pragmatic approach.
AB  - OBJECTIVE: To identify the crucial issues that arise for psychiatrists and other
      physicians when dealing with occupational disability in their patients with
      depression and to suggest practical strategies for responding more effectively to
      the challenges of this aspect of patient functioning. METHOD: We identify
      fundamental concepts in the occupational disability domain and draw crucial
      distinctions. The wider context for occupational disability is articulated,
      involving the workplace environment and the disability insurance industry.
      Research with direct relevance to clinical decision making in this area is
      highlighted. We make pragmatic suggestions for effective management of
      occupational disability in patients with depression. RESULTS: To successfully
      manage issues of occupational disability, psychiatrists and other physicians must
      understand the distinction between impairment and disability. To make this
      decision fairly and accurately, the adjudicator requires particular types of
      information from the physician, with requirements varying across short-term or
      long-term disability claims; failing to provide relevant information may cause
      substantial stress or financial harm to the patient. Balanced and collaborative
      decision making regarding whether and for how long to take work absence will
      greatly help to maintain occupational function in the long-term. Realistic
      expectations and support of the patient's sense of personal competence foster
      recovery of occupational function. CONCLUSION: Management of depression-related
      disability is challenging. Thoughtful evaluation of the patient's functional
      status, careful response to the requirements of disability determination, and a
      focus on functional recovery yield substantial benefits.

PMID- 16989107
TI  - Descriptive epidemiology of major depression in Canada.
AB  - OBJECTIVE: The Canadian Community Health Survey: Mental Health and Well-Being
      (CCHS 1.2) is the first national study to use a full version of the Composite
      International Diagnostic Interview. For this reason, and because of its large
      sample size, the CCHS 1.2 is capable of providing the best currently available
      description of major depression epidemiology in Canada. Using the CCHS 1.2 data,
      our study aimed to describe the epidemiology of major depression in Canada.
      METHOD: All estimates used appropriate sampling weights and bootstrap variance
      estimation procedures. The analysis consisted of estimating proportions
      supplemented by logistic regression modelling. RESULTS: The lifetime prevalence
      of major depressive episode was 12.2%. Past-year episodes were reported by 4.8%
      of the sample; 1.8% reported an episode in the past 30 days. As expected, major
      depression was more common in women than in men, but the difference became
      smaller with advancing age. The peak annual prevalence occurred in the group aged
      15 to 25 years. The prevalence of major depression was not related to level of
      education but was related to having a chronic medical condition, to unemployment,
      and to income. Married people had the lowest prevalence, but the effect of
      marital status changed with age. Logistic regression analysis suggested that the
      annual prevalence may increase with age in men who never married. CONCLUSIONS:
      The prevalence of major depression in the CCHS 1.2 was slightly lower than that
      reported in the US and comparable to pan-European estimates. The pattern of
      association with demographic and clinical variables, however, is broadly similar.
      An increasing prevalence with age in single (never-married) men was an unexpected
      finding.

PMID- 16989108
TI  - [Comorbidity in generalized anxiety disorder: prevalence and course after
      cognitive-behavioural therapy].
AB  - OBJECTIVE: To evaluate the prevalence and course of Axis I concurrent disorders
      in a population of patients who underwent cognitive-behavioural therapy (CBT) to
      treat their generalized anxiety disorder (GAD). METHOD: This study is a secondary
      analysis combining patients from 3 treatment studies done at Universite Laval. A
      total of 90 patients with a DSM-IV consistent GAD diagnosis received from 12 to
      16 CBT sessions to treat GAD. Symptomatology was assessed at pretest, posttest,
      and 6 months after treatment, with the Anxiety Disorders Interview Schedule, a
      structured diagnostic interview. RESULTS: Seventy-three per cent of patients had
      both GAD and a concurrent diagnosis. The most common diagnoses were simple
      phobia, social phobia, panic disorder, and major depression. CBT applied to GAD
      decreases the number of concurrent diagnoses. A panic disorder or a greater
      number of concurrent diagnoses at pretest is associated with a less efficient
      treatment at follow-up 6 months later. CONCLUSION: Patients with GAD have a high
      comorbidity rate with other Axis I disorders, but these significantly decrease
      after a short CBT aimed at GAD. Implications for GAD treatment and mechanisms
      that might explain these findings are discussed.

PMID- 16989109
TI  - Prevalence and incidence studies of anxiety disorders: a systematic review of the
      literature.
AB  - OBJECTIVE: To present the results of a systematic review of literature published
      between 1980 and 2004 reporting findings of the prevalence and incidence of
      anxiety disorders in the general population. METHOD: A literature search of
      epidemiologic studies of anxiety disorders was conducted, using Medline and
      HealthSTAR databases, canvassing English-language publications. Eligible
      publications were restricted to studies that examined age ranges covering the
      adult population. A set of predetermined inclusion and exclusion criteria were
      used to identify relevant studies. Prevalence and incidence data were extracted
      and analyzed for heterogeneity. RESULTS: A total of 41 prevalence and 5 incidence
      studies met eligibility criteria. We found heterogeneity across 1-year and
      lifetime prevalence rates of all anxiety disorder categories. Pooled 1-year and
      lifetime prevalence rates for total anxiety disorders were 10.6% and 16.6%.
      Pooled rates for individual disorders varied widely. Women had generally higher
      prevalence rates across all anxiety disorder categories, compared with men, but
      the magnitude of this difference varied. CONCLUSION: The international prevalence
      of anxiety disorders varies greatly between published epidemiologic reports. The
      variability associated with all anxiety disorders is considerably smaller than
      the variability associated with individual disorders. Women report higher rates
      of anxiety disorders than men. Several factors were found to be associated with
      heterogeneity among rates, including diagnostic criteria, diagnostic instrument,
      sample size, country studied, and response rate.

PMID- 16989110
TI  - Recent advances in the treatment of delusional disorder.
AB  - OBJECTIVE: Often considered difficult to treat in the past, even treatment
      resistant, delusional disorder is now regarded as a treatable condition that
      responds to medication in many instances. Munro and Mok previously reviewed the
      published record of its treatment to 1994. This review aims to update and extend
      their observations and to examine the impact of new second-generation
      antipsychotic agents on the treatment of this condition. METHOD: We attempted to
      gather all published reports of delusional disorder from 1994 to 2004, using
      various database strategies. We then assessed the reports for clarity and
      completeness, treatment, and outcome descriptions, thereby selecting a patient
      sample for analysis. RESULTS: Of 224 cases identified as delusional disorder,
      only 134 case descriptions provided sufficient treatment and outcome data to
      inform this review. The demographics of this sample were similar to those of the
      earlier review. Depression as a comorbid condition was more frequent than before.
      Adherence to medication regimens was seldom explicitly addressed. Most cases
      showed improvement regardless of which antipsychotic medication the patients
      received. Pimozide and other conventional antipsychotics, as well as second
      generation antipsychotics, and even clozapine, were used in many of the case
      reports. Family history of delusional disorder was seldom recorded. CONCLUSIONS:
      A positive response to medication treatment occurred in nearly 50% of the cases
      in our review, which is consistent with the earlier review.

PMID- 16989111
TI  - Re: Late-onset neutropenia with clozapine.

PMID- 16989112
TI  - Re: Characteristics of methylphenidate in a university student sample.

PMID- 16989113
TI  - Problem gambling in the Canadian North neglected.

PMID- 16989114
TI  - [Long-term clinical results with Procera AllCeram full-ceramic crowns].
AB  - The aim of this prospective clinical study was to investigate the long-term
      survival rate of Procera AllCeram full-ceramic crowns, which were fabricated with
      aluminiumoxide cores. In 50 patients, 155 Procera crowns with a conventional or
      reduced core (porcelain collar) were placed on natural abutment teeth. 78% of
      this group (39 patients with 135 crowns) were examined between May and August
      2005 according to the modified USPHS-Criteria. These crowns had been in place for
      a period of one to 92 months (mean 55 months). Almost half of the crowns were
      located in the molar region, while 28% were premolars and 24% anterior crowns.
      Due to one crown fracture the cumulative survival rate was 99% after five and
      seven years. The clinical success was achieved irrespective of the tooth
      position, tooth vitality, the preparation margin and the cementum medium used
      (composite resin or glasionomer cement). In addition, survival was neither
      influenced by the core design with reduced or conventional margin nor by the core
      thickness, which measured regularly 0.6 mm in the majority of the specimens.
      Based on the present findings, it can be concluded that Procera AllCeram is a
      predictable technique for metal-free, esthetic full-ceramic crowns in the
      anterior and posterior region.

PMID- 16989115
TI  - [Soft tissue surgery with the diode laser--theoretical and clinical aspects].
AB  - Currently laser light of different wavelengths is used for all kinds of surgical
      procedures in oral and maxillofacial surgery. In this regard especially the diode
      laser is mainly used, because of its excellent effects on oral soft tissues. On
      the basis of various oral soft tissue lesions in 40 patients the benefits of the
      diode laser in daily practice are demonstrated. Intraoperative and postoperative
      clinical findings were excellent due to the sufficient cutting abilities, the
      good coagulation effect and the extremely small zone of thermal necrosis to
      surrounding tissues. By this the diode laser has proven as an alternative
      solution to conventional electrosurgery and scalpel. The precise treatment in the
      contact application mode, which allowed an easier and more controlled guidance of
      the laser beam, was another advantage of the fiber-assisted laser system. In
      conclusion the results show that the diode laser is a useful instrument in oral
      soft tissue surgery.

PMID- 16989116
TI  - [Wide-spread subcutaneous emphysema after third molar extraction. Case report].
AB  - Two days after wisdom teeth removal an eighteen-year-old man complained of a
      painful subcutaneous neck emphysema. CT scans showed that the air collections
      were expanding close to the mediastinum. A conservative intravenous medication
      with broadspectrum antibiotics was administered and within three days the
      symptoms resolved completely without any surgical intervention. Subcutaneous
      emphysema after dental treatment can develop into infectious, potentially lethal
      fasciitis and mediastinitis. Therefore it must be thoroughly examined and
      immediately operated on, if suspicious of an infection.

PMID- 16989117
TI  - [The difficulty of measurement of placebo effect].
AB  - The use of placebos within controlled clinical trials for the placebo effect;
      last 50 years suggests that psycho-physiological effects can be objectified and
      measured. These are related to the therapeutic measurement; results covered by
      the term "placebo effect". Since Beecher's pioneer article in 1955, this effect
      is recognised and cited in randomised clinical trial; medical articles as being
      on average 35% effective on the majority of symptoms. However, the meaning of
      these measurement artefact is questionable. For example, it does not take into
      account the spontaneous evolution of symptoms and diseases. In fact, the placebo
      effect is not the effect measured in the group treated by the placebo. The
      clinical trial drug controlled against placebo does not make it possible to
      measure what is thus wrongly called "the placebo effect". Is it possible then to
      measure and to objectify what is called the placebo effect? And if that is
      possible, how? This article calls into question the extent of the placebo effect
      evaluated by means of controlled clinical trials, without denying its importance
      in medical practice. Firstly it raises the epistemological problem of the real
      possibility, via experimentation, of objectifying psychological therapeutic
      effects. And secondly, the question is also raised of the interest for medical
      care of objectifying those effects.

PMID- 16989118
TI  - [Is there a role for calcium antagonists when beta-adrenergic blockade therapy is
      contraindicated in post-myocardial infarction?].
AB  - The purpose of this paper is to examine the eventual benefits of treatment with
      calcium channel blockers in post-myocardial infarction, through an overview of
      main placebo-controlled trials that have been conducted to test this therapeutic
      in acute coronary syndromes. It appears obvious that the vast majority of these
      trials was conducted in the pre-reperfusion era and failed to demonstrate a
      reduction in mortality. To conclude, the superiority of a therapy with calcium
      antagonists over a placebo in the management of post-myocardial infarction
      remains unknown. In contrast, adverse effects associated with the prescription of
      calcium antagonists are well known.

PMID- 16989119
TI  - [Antifungals cellular targets and mechanisms of resistance].
AB  - Antifungals of systemic use for the treatment of invasive fungal infections
      belong to four main chemical families which have globally three cellular targets
      in fungal cells: fluorinated pyrimidines act on deoxyribonucleic acid (DNA)
      replication and protein synthesis; polyenes and azoles are toxic for ergosterol
      and its biosynthetic pathway; lipopeptides inhibit the synthesis of cell wall
      beta glucans. The resistance mechanisms that are developed by some fungi begin to
      be well understood particularly in Candida yeasts. The underlying bases of these
      mechanisms are either mutations that modify the antifungal target, or that block
      access to the target, and, on the other hand, the overexpression of genes
      encoding the target, or some membrane proteins involved in the active efflux of
      antifungal drugs.

PMID- 16989120
TI  - [Methods for in vitro antifungal susceptibility testing].
AB  - During the last years, a large amount of work has been completed to improve the
      methods used for in vitro antifungal susceptibility testing. Reference techniques
      are currently available both for yeasts and filamentous fungi, but in some
      instances, technical improvement are needed. Etest is another well standardized
      method that can be used as an alternative on a routine basis in the clinical
      microbiology laboratory. Studies of in vitro-in vivo correlations have led to the
      definition of susceptibility breakpoints for yeasts for fluconazole,
      itraconazole, and flucytosine.

PMID- 16989121
TI  - [Pharmacokinetics-pharmacodynamics of antifungal drugs. Consequences for
      therapeutic drug monitoring].
AB  - Despite pharmacokinetic-pharmacodynamic relationships were clearly evidenced for
      antifungal drugs by the use of experimental models, few target plasma
      concentrations could be determined from studies performed in patients. The main
      causes explaining this lack of data are reviewed and the possible use in humans
      of the parameters obtained from animal models is discussed.

PMID- 16989122
TI  - [Pharmacokinetic of antifungal drugs in order to optimize their administration].
AB  - Antifungal drugs for treating systemic mycoses are flucytosine, amphotericin B,
      azoles and caspofungin. Their pharmacokinetics and pharmacodynamics are reviewed
      in order to determine the optimal modalities of their administration and the best
      dosing regimen for several populations: neonates, infants, patients with renal or
      liver disease, patients with hemodialysis or hemofiltration.

PMID- 16989123
TI  - [Emerging azole antifungals].
AB  - Azoles have maintained a key role in the treatment of invasive fungal infections
      which have a growing importance, especially in immunocompromised patients.
      Because of its good activity and safety, fluconazole has becoming the treatment
      of choice for invasive candidiasis, except those caused by Candida glabrata and
      C. krusei. In contrast, itraconazole which is active against Aspergillus sp has
      limited use for the treatment of invasive mould infections due to the high
      variability of its bioavailibility. Voriconazole is active against a broad range
      of fungal pathogens including Aspergillus sp and other molds, except Zygomycetes.
      Voriconazole is used as first-line therapy for invasive aspergillosis and for
      infections caused by Fusarium and Scedosporium. It is available in both oral and
      intravenous administration. Posaconazole has similar in vitro activity but
      currently only the oral form is available. Its main indication is refractory
      aspergillosis or intolerance to previous treatment. Posaconzole will be very
      useful for long-term therapy of zygomycetes infections.

PMID- 16989124
TI  - [Lipid formulations of amphotericin B in the management of invasive fungal
      infections].
AB  - Three lipid formulations of amphotericin B have been developed: amphotericin B
      colloidal dispersion, amphotericin B lipid complex, and liposomal amphotericin B.
      These three compounds differ by their lipid composition and therefore by their
      physical characteristics, their pharmacokinetics, and their safety and efficacy
      profile. There is a consensus to accept reduced toxicity of these formulations,
      especially reduced, but not absence of, renal toxicity as compared to
      amphotericin B deoxycholate. Few well-designed studies have been conducted and
      none of them demonstrated convincingly superiority in term of efficacy of any of
      the lipid preparations over amphotericin B deoxycholate. Recently a double blind
      randomized study compared a standard dose of 3 mg/kg/d of liposomal amphotericin
      B and a loading dose (10 mg/kg/d for 14 days and then the standard dose) in
      primary therapy of invasive filamentous fungal infections, mainly aspergillosis.
      Response rate at end of randomized therapy as well as survival at 12 weeks was
      numerically superior in the standard dose arm but this difference was not
      statistically significant. Lack of benefit of high dose liposomal amphotericin B
      in aspergillosis cannot yet be extrapolated to other filamentous fungal
      infections. Nephrotoxicity was substantially higher in the loading dose arm and
      this contraindicates its use in clinical practice.

PMID- 16989125
TI  - [Paediatric specificity of antifungals use].
AB  - Specificity of antifungals use in paediatric patients is linked to mycoses
      epidemiology in this population. Pharmacokinetics vary with patient age. Although
      studies are in progress, pharmacokinetic data in children are limited in number
      for most antifungals. Among antifungal agents, those approved in France for use
      in children are rare. Adverse event frequency can differ in children, as compared
      to frequency in adults, and drug interaction should be a major worry. Relative
      interest and cost of available forms in the paediatric population in not always
      taken into account. For each different situation, an optimal strategy of
      antifungals use in children should be determined.

PMID- 16989126
TI  - Antifungal combinations: where do we stand?

PMID- 16989127
TI  - [Use of topical antifungal agents].
AB  - Topical antifungal agents are not absorbed when given orally. They act by direct
      contact on the fungus, this type of action requires the simultaneous presence of
      antifungal and fungus for a minimum of time. There are a large number of
      compounds belonging to different families of antifungals: polyens, azoles,
      allylamine and morpholine and antiseptic substances. The treatment of
      oropharyngeal candidiasis is based on topical antifungal agents: amphotericin B
      or nystatin, imidazoles such as clotrimazole or miconazole. Systemic antifungal
      agents are indicated in case or poor compliance to topical agents, in prophylaxis
      of highly relapsing disease, in oesophageal candidiasis and in Candida
      onychomycosis. A topical antifungal agent is the first choice to treat Candida
      intertrigo. In any case predisposing factors should be eradicated or amended.
      Infection to Malassezia spp. are treated topically with azoles or selenium
      sulphur. Oral ketoconazole is an alternative in severe cases. Dermatophytosis
      requires a systemic antifungal treatment such as terbinafine in chronic, dry,
      moccassin type palmoplantar infection and for onychomycosis. Intertrigo and tinea
      corporis are treated with topical agents such as azoles, terbinafine or
      tolnaftate. Tinea capitis responds to oral griseofulvine, however a topical
      antifungal must be added to eradicate contagious conidia. Whatever the
      localisation is, an other superficial site of infection must be looked for and a
      source of infection should be investigated and eradicated.

PMID- 16989128
TI  - [Severe renal adverse events with arylcarboxylic non-steroidal anti-inflammatory
      drugs: results of a eight-year French national survey].
AB  - The non-steroidal anti-inflammatory drugs (NSAID) especially the arylcarboxylic,
      are widely prescribed for their different properties. The renal adverse events
      are rare but often serious. We have reviewed the French experience for the
      following eight years period: January 1995 to December 2002. Three hundred and
      nine cases have been reported to the French Pharmacovigilance system during that
      period including 275 adults, 29 children and 5 new-born babies. In 247 cases
      (80%), the presentation was an acute renal failure occurring few days after
      treatment onset but not always of the prerenal type. Overall 34 patients needed
      one or more dialysis session; the majority recovered either completely or
      partially, but nevertheless, we had to deplore 5 deaths. These major renal
      complications were observed with all available NSAID on the French market,
      including ibuprofen which was often prescribe as pain-reliever. With this data
      together with international information, the French Drug Agency decided to modify
      the summary of products characteristics of these NSAID.

PMID- 16989129
TI  - Continuity: a person or a process?

PMID- 16989130
TI  - Understanding neonatal bowel obstruction: building knowledge to advance practice.
AB  - Providing care to neonates with bowel obstruction requires a basic understanding
      of gastrointestinal (GI) anatomy and functional landmarks as well as knowledge of
      the pathophysiology associated with intestinal blockage. Early recognition and
      prompt diagnosis necessitate astute assessment of common presenting symptoms and
      accurate interpretation of diagnostic investigations. Initial medical management
      is focused primarily on gastric decompression and maintenance of fluid and
      electrolyte balance. This article describes features of the neonatal GI tract and
      discusses common causes of neonatal bowel obstruction.

PMID- 16989131
TI  - Caring for the newborn with an omphalocele.
AB  - An omphalocele, a ventral defect of the umbilical ring resulting in herniation of
      the abdominal viscera, is one of the most common congenital abdominal wall
      defects seen in the newborn. Omphaloceles occur in 1 in 3000 to 10,000 live
      births. Associated malformations such as chromosomal, cardiac, or genitourinary
      abnormalities are common. Postnatal management includes protection of the
      herniated viscera, maintenance of fluids and electrolytes, prevention of
      hypothermia, gastric decompression, prevention of sepsis, and maintenance of
      cardiorespiratory stability. A primary or staged closure approach may be used to
      repair the defect. Some giant omphaloceles require a skin flap or nonoperative
      management approach, hoxvever. Immediate postoperative complications, usually
      related to significant changes in intra-abdominal pressures, include compromise
      of interior venous blood return and hemodynamic and respiratory instability due
      to diaphragmaric elevation. Complications occur more frequently with giant
      defects. Potential short-term complications include necrotizing enterocolitis,
      prolonged ileus, and respiratory distress. Long-term complications include
      parenteral nutrition dependence, gastroesophageal reflux, parenteral nutrition
      related liver disease, feeding intolerance, and neurodevelopmental delay.
      Overall, advances in surgical therapies and nursing care have improved outcomes
      for infants with omphaloceles; survival rates for those with isolated
      omphaloceles are reported at 75 to 95 percent. Infants with associated anomalies
      and giant omphaloceles have the poorest outcomes.

PMID- 16989132
TI  - Partnering with parents: establishing effective long-term relationships with
      parents in the NICU.

PMID- 16989133
TI  - Pain assessment and pharmacologic management for infants with NEC: a
      retrospective chart audit.

PMID- 16989134
TI  - Octreotide.
AB  - The use of SC or IV octreotide, a long-acting synthetic analog of somatostatin,
      provides a promising pharmacologic approach to reducing drainage in selected
      patients with a congenital or postoperative chylothorax, who do not respond to
      conservative treatment strategies. Prompt institution of octreotide therapy after
      surgery in patients with significant drainage or the formation of chyle may
      reduce the expense and morbidity associated with a prolonged hospital stay. Given
      the individual variability in patient response to octreotide and the limited
      clinical data regarding its use in the pediatric population, octreotide therapy
      must be individualized with careful consideration being given to possible
      benefits versus inherent risks.

PMID- 16989135
TI  - Congenital chylothorax: a case study.
AB  - Congenital chylothorax, an uncommon cause of respiratory distress in the neonate,
      is diagnosed initially by prenatal ultrasound or postnatal x-ray and definitively
      by evaluation of the fluid in the pleural space. The etiology is not well
      understood, and reaccumulation of fluid can occur. Thoracentesis and chest tube
      placement may be required to support respiratory status. Conservative treatment,
      which may be tried for up to five weeks, includes diet and should be attempted
      before surgical intervention. Nutritional status, along with fluids and
      electrolytes, needs to be monitored closely.

PMID- 16989136
TI  - Moving ahead in addressing challenges that face nursing.

PMID- 16989137
TI  - Medical special needs focus for Texas.

PMID- 16989138
TI  - TNA testifies: faculty salaries must increase.

PMID- 16989139
TI  - [Plantago ovata].
AB  - Plantago ovata is a high fibre bulk forming laxative. It absorbs water and
      expands to provide increased bulk and moisture content to the stool. The
      increased bulk encourages normal peristalsis and bowel motility. Clinical
      Indications: Constipation, Fecal Incontinence, Hemorrhoids, Ulcerative Colitis,
      Appetite, Hyperlipidemia, Diabetes mellitus.

PMID- 16989140
TI  - Posterior leaflet preservation during mitral valve replacement for rheumatic
      mitral stenosis.
AB  - Mitral valve replacement with posterior leaflet preservation was shown beneficial
      for postoperative left vetricular (LV) performance in patients with mitral
      regurgitation. Some authors find it beneficial even for the long term LV
      function. We investigated a long term effect of this technique in patients with
      rheumatic mitral stenosis. We studied 20 patents with mitral valve replacement
      due to rheumatic mitral stenosis, in the period from January 1988 to December
      1989. In group A (10 patients) both leaflets and coresponding chordal excision
      was performed, while in group B (10 patients) the posterior leaflet was
      preserved. In all patients a Carbomedics valve was inserted. We compared clinical
      pre and postoperative status, as well as hemodynamic characteristics of the valve
      and left ventricle in both groups. Control echocardiographyc analysis included:
      maximal (PG) and mean (MG) gradients; effective valve area (AREA); telediastolic
      (TDV) and telesystolic (TSV) LV volume; stroke volume (SV); ejection fraction
      (EF); fractional shortening (FS) and segmental LV motion. The mean size of
      inserted valve was 26.6 in group A and 27.2 in group B. Hemodynamic data: PG
      (10.12 vs 11.1); MG (3.57 vs 3.87); AREA (2.35 vs 2.30); TDV 126.0 vs 114.5); TSV
      (42.2 vs 36.62); SV (83.7 vs 77.75); EF (63.66 vs 67.12); FS (32.66 vs 38.25).
      Diaphragmal segmental hypokinesis was evident in one patient from group A and in
      two patients from group B. In patients with rheumatic stenosis, posterior leaflet
      preservation did not have increased beneficial effect on left ventricular
      performance during long-term follow-up. An adequate posterior leaflet
      preservation does not change hemodynamic valvular characteristics even after long
      term follow-up.

PMID- 16989141
TI  - [The role of PCR in detection of cytomegalovirus in blood and urine of
      transplanted patients].
AB  - Rapid and reliable laboratory diagnosis of cytomegalovirus (CMV) infection in
      transplanted patients becomes more significant considering possible prevention or
      moderation of CMV disease. The aim of this study was comparison of CMV isolation
      in cell culture and CMV detection by PCR in blood and urine samples of
      transplanted patients. The study comprised 21 patients undergoing
      immunosuppressive therapy after renal or bone marrow transplantation. MRC-5 cell
      culture was used for viral isolation. Inoculated cultures were maintained for 4
      weeks or until appearance of specific cytopathic effect (CPE). Primers used in
      PCR were specific for the sequence within egzon 4 of immediate-early 1 (IE-1)
      gene. Presence of anti-CMV IgG and IgM antibodies was determined by ELISA. PCR
      was more sensitive for blood (4/21) and urine samples (3/19) than cell culture
      method--blood (0/21) urine (2/19). Statistically significant correlation was not
      shown between presence of CMV(determined by PCR) in blood and urine of the same
      patient.

PMID- 16989142
TI  - [Hepatobiliary scintigraphy in evaluation of liver transplant function].
AB  - The aim of the study is evaluation of hepatocellular function, as well as
      morphology and patency of the biliary three of the liver transplants by dynamic
      hepatobiliary scintigraphy. The study was performed in 10 controls and 10
      patients after orthotopic transplantation (up to two years). Sixty minutes
      dynamic acquisition (1 frame/min) was performed with scintillation camera after
      injection of 360 MBq 99mTc-diethyl- IDA. Hepatobiliary scintigrams were analysed
      for morphology, and parenchymal and hepatobiliary TA curves were generated and
      analysed as regard to the time to maximal acitivity (Tmax) and the time to half
      of maximum acitivity (T1/2). Uptake of the radiopharmaceutical was slightly but
      not significantly delayed (Tmax=18.5 +/- 2.9 min) in comparison to the controls
      (Tmax=14.2 +/- 3.4min), while excretion was significantly prolonged (T1/2=59.5 +/
      12.1 min) than physiological (Tmax=34.2 +/- 4.1min). Intrahepatic bile flow was
      nonsignificantly prolonged (Tmax=31.3 +/- 3.7 min) in comparison to the controls
      (Tmax=25.7 +/- 3.5 min) while extrahepatic one is high significantly prolonged
      (T1/2=89.0 +/- 14.3 min) than physiological (T1/2 =45.0 +/- 7.2 min). Biliary
      phase of hepatobiliary scintigraphy showed increased accumulation of
      radiopharmaceutical in the left (n=1) or right (n=2) hepatic duct. Radionuclide
      methods are noninvasive, and apear to be sensitive and valuable for the
      monitoring of liver transplants.

PMID- 16989143
TI  - [Ambulatory surgery of umbilical, epigastric and small incisional hernias: open
      preperitoneal flat mesh technique in local anaesthesia].
AB  - INTRODUCTION: The dilemma whether to use the mesh or non mesh technique in the
      management of umbilical, epigastric and small incisional hernia is slowly fading
      away. The open preperitoneal "flat mesh" technique performed as ambulatory
      surgery may be one of the solutions. THE AIM: The aim of this retrospective study
      is to present the results of open preperitoneal "flat mesh" technique in the
      management of umbilical, epigastric and small incisional hernia within MATERIAL
      AND METHODS: This study included 34 patients (11 of them with umbilical, 13 with
      epigastric and 8 of them with small incisional hernia) operated by one surgeon in
      the period January 2004-January 2006. RESULTS: The median operative time was 52
      minutes for umbilical hernia's, 43 minutes for epgastric and 54 minutes for
      incisional hernia's. The ambulatory surgery was performed at 91% of patients. The
      median hospitalization was 4h for patients with umbilical hernia's, 3,7h for
      patients with epigastric and, 7,7h for patients with small incisional hernia. The
      follow up is 10,5 months. Apart of one superficial infection other complications
      were absent. CONCLUSION: The open preperitoneal "flat mesh" technique performed
      in local anesthesia as an ambulatory surgery provides good results in the
      management of umbilical, epigastric and small incisional hernia.

PMID- 16989144
TI  - [Retrohepatic veins of the posterior section of the right hepatic lobe-
      terminology and surgical significance].
AB  - Three main hepatic veins: right, middle and left are constant, but there is a
      variable number of retrohepatic vessels called accessory or minor hepatic veins.
      The most important of them are veins reffered to as middle right hepatic vein
      (MRHV) draining segment VII and inferior right hepatic vein (IRHV) draining
      segment VI. The incidence of large MRHV and IRHV reaching or exceeding a caliber
      of 5mm, their arrangement in the liver and drainage territories were investigated
      in our collection of 142 injection-corrosion specimens of the liver. In 1/5 of
      the cases with large IRHV this vein drains small part of segment VI, sometimes
      its insignificant marginal part so it couldn't be used for segment VI
      preservation when it is necessary. A precise knowledge of the vein anatomy of
      right posterior sector of the liver and its vein drainage territories is very
      important during complex dissections of the retrohepatic areas, resections and
      preservation liver parenchima.

PMID- 16989145
TI  - [Splenic artery aneurysms].
AB  - Although the third most frequent aneurysm in the abdomen, after aneurysms of the
      aorta and iliac arteries, and most frequent aneurisms of visceral arteries,
      splenic artery aneurysms are rare, but not very rare. Thanks to the new imaging
      techniques, first of all ultrasonography, they have been discovered with
      increasing frequency. We present a series of 9 splenic artery aneurysms. Seven
      patients were female and two male of average age 49 years (ranging from 28 to 75
      years). The majority of afected women were multiparae, with average 3 children
      (ranging from 1 to 6). One patient had a subacute rupture, and 2 had ruptures
      into the splenic vein causing portal hypertension. The spleen was enlarged in 7
      out of 9 patients. The average size of aneurysms was 3,2 cm (ranging from 2 to 8
      cm). The preoperative diagnosis of splenic artery aneurysm was established in 6
      patients while in 3 patients aneurism was accidentally found during other
      operations, during splenectomy in 2, and during the excision of a retroperitoneal
      tumour in 1 patient. Aneurysmectomy was carried out in 7 patients, while a
      ligation of the incoming and outcoming wessels was performed in 2 patients with
      arteriovenous fistula. Splenectomy was performed in 6 patients, while pancreatic
      tail resection, cholecystectomy and excision of the retroperitoneal tumor were
      performed in 3 patients. Additional resection of the abdominal aortic aneurysm
      with reconstruction of aortoiliac segment was performed in 2 patients. There were
      no mortality and the postoperative recovery was uneventful in all patients.

PMID- 16989146
TI  - [Endotracheal intubation in prehospital treatmen of children with craniocerebral
      injuries].
AB  - BACKGROUND: Intubation and airway control of injured children is of vital
      importance, but despite its advantages is associated with meny risks when is
      performed outside the hospital and by the untrained physicians. Aim of this study
      was to determine the importance for the survival of the children with
      craniocerebral injuries, and also for final outcome of treatment. METHODS: This
      study is a clinical, partly prospective, partly retrospective that includes 60
      patients (two groups with 30 patients) with isolated craniocerebral injures, aged
      up to 17 years, and with GCS under 8, that did not require surgical treatment.
      The first group included patients that were endotracheal intubated, and the other
      group included patients that were not intubated. RESULTS: Theree was no
      statistically difference between groups regarding the sex, age and GCS. Regarding
      the endotracheal intubation there was a statistically significant difference, in
      the first group 86,7% of the patients were intubated during the prehospital
      treatment, while 16,7% of the patients from group II were intubated. A greater
      percentage of patients from group I underwent controlled (66,7%) or assisted
      (20%) mode of ventilation, and 13,3% of patients were on spontaneus breathing.
      CONCLUSION: Endotracheal intubation should be performed by an experienced
      physician with an adequate equipment.

PMID- 16989147
TI  - The impact of diabetes mellitus on postoperative morbidity in laryngeal surgery.
AB  - The main aim of this study was to analyse risk factors of postoperative morbidity
      after extended laryngeal surgery comparing patients with diabetes mellitus and
      non-diabetic patients. In retrospective study 69 patients (63 male and 6 female),
      who underwent partial laryngo-pharyngectomy and total laryngectomy between 2003
      and 2004, were evaluated. 13 % of the total group of examined patients had
      concurrent diabetes, while 87% were nondiabetic patients. We performed partial
      laryngopharyngectomy in 39 out of 69 patients (56.5%) and total laryngectomy in
      30 patients (43.5%). Secondary wound infections (88.9%) and pharyngocutaneus
      fistula (44.5%) had a significantly higher rate in diabetic patients (p<0.001).
      Among diabetics the cases with intraoperative or postoperative blood transfusions
      were more frequent--44.4%(p<0.001). Diabetic patients with laryngectomy
      procedures had more frequently prolonged postoperative anemia (55.5%, p<0.001)
      and electrolitic disbalance (66.6%, p<0.001). Our results have confirmed that
      diabetes mellitus is an important independent general clinical factor, which
      increases postoperative morbidity and hospitalization time in laryngeal surgery.
      Our data indicate the need to make a very serious plan and clinical assesment for
      laryngeal surgical therapy in diabetic patients.

PMID- 16989148
TI  - [Surgical methods for the treatment of breast phyllodes tumors--a report of 319
      cases].
AB  - Breast phyllodes tumors (FT) belong the fibroapitelial group of breast tumors
      arising in terminal ductulo-lobular unit (TDLU). Their incidence do not exceed 1%
      of all breast tumors. Biologicaly they can be divided into benign, borderline and
      malignant group. Incomplete tumor excision can be the reason for local
      reccurence. Malignant form of FT metastazise hematogenous most often in the lung.
      There is no uniform surgical opinion about the treatment FT. METHODS: We analyzed
      histopathology features of 319 FT of the breast surgicaly removed on Departement
      of surgery Institut of oncology and radiology of Serbia between 1.1.1985.
      31.12.1994. Retrospective study of surgical treatment 84 patients with FT of the
      breast (69 benign, 4 borderline and 11 malignant) and 5 year follow up after
      surgery we analysed. RESULTS: local reccurence after surgery was found in 17
      (20,2 %) patients(14 benign , 2 borderline and 1 malignant FT), pulmonary
      metastases in 6 (7,1%) patients with malignant FT. DFI was 21,3 months for local
      reccurences and 25,1 months for pulmonary metastases. DFS for al forms of FT was
      71 % (p =0,7104) in 5-year follow up. CONCLUSION: According to biological
      behavior we propose wide excision for benign and borderline forms and simple
      mastectomy for malignant FT, and voluminous benign and borderline forms. Axillary
      disection is not necessary because lymphatic spread of malignant FT is
      unfrequent.

PMID- 16989149
TI  - [Cystic artery anatomy characteristics in minimally invasive surgical
      procedures].
AB  - Large patient series undergoing laparoscopic cholecystectomy fail to show
      anatomic variations which lead to intraoperative bleeding. METHOD: Cadaver
      material was used and corrosion casting and postmortem arteriography were
      employed. RESULTS: Three types of cystic artery were devised according to the
      results. Type 1 normal anatomy. Type 2 more than one artery in Calots triangle
      and Type 3 no artery in Calots triangle. DISCUSSION: only 40% of the second
      cystic artery is present in Calots triangle. The short second cystic artery is
      characteristic and its most often origin is from a segmental branch of the right
      hepatic artery. When there is no artery in Calots triangle its origin unusual,
      and the artery is either on the postero-lateral side of the cystic duct or it
      approaches the gallbladder through hepatic tissue. The specifics of MIS approach
      make changes in the way we understand the anatomic variations of the cystic
      artery. The classification is a result of practical experience and anatomical
      investigations.

PMID- 16989150
TI  - [The tunneled supraclavicular island flap--a fasciocutaneous flap for head and
      neck reconstructions].
AB  - Reconstructive procedures in the head and neck region use a wide range of flaps
      for defect closure. The methods range from local, mostly myocutaneous flaps and
      skin grafts to free microsurgical flaps. To ensure a satisfactory functional and
      aesthetic result, good texture and color of the flap are always essential.
      Moreover, the donor-site defect needs to be reduced, with no resulting functional
      or aesthetic impairment. We have found that the shoulder is a region providing an
      optimum skin texture match to the neck and face. Fasciocutaneous island flap,
      nourished by the supraclavicular artery is used purely as a subcutaneously
      tunneled island flap. The tunneling maneuver significantly improves the donor
      site by reducing scarring. The flap is characterized by a long subcutaneous
      pedicle of up to 20 cm. The pivot point is in the supraclavicular region and
      allows the flap to be used in the upper chest, neck, chin, and cheek. In this
      article we present clinical cases in reconstructive procedures with
      supraclavicular flap and its expanded indications.

PMID- 16989151
TI  - [Increase of newly--detected in situ cancers in non-palpable breast lesions].
AB  - Great importance in detecting cancer in the phase of in situ lays in the fact
      that the epithelial layer is deprived of blood and lymph vessels, so metastases
      may develop only when basal membrane has been broken. This paper includes 46
      operated women in whom it preoperatively had been verified suspect non-palpable
      lesion. The preoperative diagnostics included use of high- resolution
      mammography, aimed mammography, palpatory examination, as well as fine-needle
      aspiration (FNA), biopsy and cytologic analysis of the sample. The methodology of
      this work implies the use of stereotaxic marking, specimen mammography and ex
      tempore pathohistology analysis. Out of 46 investigated patients in clinical
      stage T0N0M0, in whom there were no signs of malignant disease, and according to
      suspect lesion of initial screening mammography, malignant lesions of breast
      tissue were diagnosed in 19 patients (41%) intraoperatively. Three of these
      lesions (15,8%) were histopathologically verified as in situ. Comparing our
      results with data of the Institute of oncology and radiology of Serbia hospital
      registry (IORS) for the year 2001, from 1173 patients registered with malignant
      lesions, only 16 ones (1,4%) had in situ cancer, operated on the basis of the
      suspect mammography of clinical stage T0N0M0. Statistically significant
      difference was found related to the number of detected cancers in this early
      phase of the breast malignant disease. This limits surgical intervention to
      tumorectomy, with preservation of the remaining breast tissue, what brings to
      healing, justifying in that way, screening examinations and routine application
      of the most contemporary diagnostic procedures.

PMID- 16989152
TI  - [Outcome of Burch retropubic urethropexy and the effect of concomitant abdominal
      hysterectomy].
AB  - A prospective follow-up stady was performed to evaluate the effect of Burch
      colposuspension alone and a concomitant abdominal hysterectomy with Burch
      colposuspension. Twenty seven women underwent Burch colposuspension and 34 women
      colposuspension with abdomina hysterectomy. Subjective outcame was assessed with
      questionaire at 4 weeks, 6 months and 1 year. In the 1 year follow-up 81,4% were
      subjectively cured or improved in the Burch group and 76,4% in the hysterectomy
      group. No statistically significant difference in the frequency of any subgroup
      of complications was found.

PMID- 16989153
TI  - [Myomectomy by vaginal route].
AB  - Myomectomy by vaginal route is the least invasive of all methods for myoma
      removal. Compared to classical, abdominal myomectomy, it has numerous advantages,
      especially in cases of fundal and posterior wall myomas, but still it is
      relatively rarely performed. This study provides an analysis of operative and
      postoperative course of patients subjected to myomectomy by vaginal route in the
      period from 01/01/2003 to 01/11/2005 as well as the corresponding control group
      of patients which had undergone classical, abdominal myomectomy. The study points
      out to significance and advantages of application of surgical technique for
      removal of myoma through the posterior wall of the vagina as opposed to
      classical, abdominal myomectomy. Transvaginal myomectomy eliminates trauma of
      laparotomy, intraoperative blood loss is reduced, postoperative complications are
      down to minimum, postoperative recovery is shorter, and so is the number of days
      spent in hospital. Thus, by performing this type of surgery, a positive cost
      benefit effect is obtained not only for the patient but for health authorities as
      well.

PMID- 16989154
TI  - Endoscopic removal of pedunculated leiomyoma of the sigmoid colon (case report
      and literature review of dignostic and treatment options).
AB  - Colonic leiomyoma are remarkably rare cause of colonic symptoms in clinical
      practice. They constitute only 3% of gastrointestinal leiomyomas and complete
      endoscopic removal of the tumour can be a problem because of its submucosal
      origin. We describe a 62-year female patient with a 8 mm leiomyoma of sigmoid
      colon that was successfully removed by conventional endoscopic snare
      electrocauterisation, without complications.

PMID- 16989155
TI  - [Acute renal failure after cesarean section as a consequence of hematoma of the
      retropubic space of Retzius].
AB  - Acute renal failure is rare postoperative complication of cesarean section.
      Postrenal acute renal failure is corectible ant it shoud be done immediately in
      order to avoid secundary destruction of renal parenchim. Surgical techniques
      shoud be directed to achieve adequat haemostasis, espetialy at low transverse
      Pfannenstiel incision, as well as in tender manipuliating with tissues to prevent
      unnecessery formation of dead space and tissues devitalisation. Authors are
      presenting the case of acute renal failure after cesarean section as a
      consequence of hematoma of the retropubic space of Retzius and way of treatment.

PMID- 16989156
TI  - [TGF-beta1 gene polymorphism in chronic obstructive pulmonary disease].
AB  - Gene polymorphism is often responsible for occurrence of some chronic diseases.
      It has not been clarified, why only 15-20% of smokers suffer from chronic
      obstructive pulmonary disease (COPD). TGF-beta1 gene polymorphism has been
      postulated as one of possible genetic risk factors. The aim of our study was to
      evaluate TGF-beta1 gene polymorphism in codons 10 and 25 in COPD patients in
      comparison to healthy controls. Thirty six COPD patients and 60 healthy persons
      entered the study. The distribution of TGF-beta1 genotypes in codon 10 was as
      follows in COPD group: T/C--50%, T/T--25% and C/C--25% in control group: 45%, 42%
      and 13% respectively. The distribution of genotypes in codon 25 in COPD patients
      was: G/G 86% and G/C 14%, in control group 83% and 17% respectively. There were
      not statistically significant differences between evaluated groups with regard to
      both polymorphisms. Moreover, in group of 27 smokers without COPD the
      distribution of the analysed TGF-beta1 gene polymorphism was similar to that in
      COPD group. After adjustment to sex, age and smoking index, in the logistic
      regression model, we can not confirm the hypothesis that TGF-beta1 gene
      polymorphisms in codons 10 and 25 might be significant risk factors of COPD.

PMID- 16989157
TI  - [Incidence of tuberculosis in Poland 2004 and its trends].
AB  - Tuberculosis has been a major public health problem in Poland for many decades.
      The aim of this investigation was to evaluate incidence of TB in Poland in 2004
      and to examine trends of TB incidence in last decade. In 2004. decrease of
      tuberculosis notification rates in Poland has continued. In this year 9.493 new
      tuberculosis cases notified in Poland. Incidence rate was 24.9 per 100.000
      population with the large differences in notification rates between
      voivodships/geographic region/ from 14.5 (The West) to 36.0/100.000 The East).
      Between 1994-2004 notification rates decreased by 42%. New cases represented
      87.8% of all TB cases. Pulmonary cases represented 91.6% of all cases of which
      59% were bacteriologically confirmed (smear and/or culture positive). 37% of all
      TB pulmonary cases were sputum smear positive, which is rather low but similar to
      previous years. Low proportion--8.4% of extrapulmonary cases which is observed
      for many years may indicate inadequacies in diagnosis and registration of this TB
      form. Pediatric TB cases--incidence 1.9--represented 1.3% of all cases notified
      in Poland. The incidence of tuberculosis increases with age from 1.9 in children
      up to 51.7 among 65 and older patients. Median age of TB patients is between 50
      54 years. The incidence of men 34.1 is two times higher than in woman (16.2) and
      in rural population it is near the same: 25.5 and in urban 24.5. Among of all the
      TB pulmonary cases there were 395 cases with resistance to at least one drug. In
      these cases was about 100 MDR cases. Registered 260 TB cases among prisoners-
      2.7% of overall cases, and 16 TB cases were among foreigners. CONCLUSIONS: In
      last decade decrease of TB has continued. The incidence of tuberculosis in Poland
      was about two times higher than mean incidence for Enlarge European Union. The
      distance between Poland and EU countries with lowest incidence is estimated for
      20-25 years.

PMID- 16989158
TI  - [Application of the molecular test PCR multiplex for identification of
      Mycobacterium bovis BCG strains].
AB  - In our last paper (18) we described the problem of proper microbiological
      identification of BCG strains and how important is distinguishing vaccine strain
      from virulent strains of Mycobacterium tuberculosis complex. We have suggested
      the modern algorithm of BCG strains identification including mycolic acids
      profile by HPLC and 14C PZA resistance methods. These methods allowed us to made
      fast and accurate microbiological identification of side effects of BCG vaccine
      in the children. Identification of BCG by HPLC is possible within one working day
      compared with 3-4 weeks required for conventional methods. However both methods
      need very expensive instruments like HPLC and/or Bactec-460 Tb radiometric
      system. Presently we have evaluated molecular test based on the analyzis of the
      region RD1 encoding a 9.5-kb fragment. This fragment is deleted in all BCG
      substrains (6) and present in all human and bovine virulent strains. To evaluate
      this method for the rapid and specific detection of BCG, a large strain
      collection (32 strains) representating M. bovis BCG (vaccine strains and strains
      isolated from the children in case of adverse reactions after vaccination) M.
      bovis and M. tuberculosis from own collection was analyzed. RD1 was present in
      all 15 M. tuberculosis and M. bovis tested strains and deleted in 17 of 18 BCG
      strains. The multiplex PCR method was 100% sensitive and specific for the
      identification of BCG among strains of the Mycobacterium tuberculosis complex.
      Multiplex PCR can be used as a diagnostic test and has significant advantages
      over existing methods.

PMID- 16989159
TI  - [Change of patients profile hospitalized because of pulmonary sarcoidosis in
      Department of Pneumonology in Zabrze (Poland) in 1976-80 and in 1996-2000].
AB  - The comparision of two groups of patients with pulmonary sarcoidosis hospitalized
      in Department of Pneumonology Silesian Medical School of Medicine in Zabrze in
      1976-1980 (n=120) and 20 years later i.e. in 1986-2000 (n=190) was done. We have
      noticed, that in comparision with period of 1976-80 the mean age of patients
      hospitalized in 1986-2000 has significantly increased (41.6 vs. 37.0 p < 0.05)
      and percentage of females has significantly diminished (50.0% vs. 63.3% p <
      0.05). No change in age structure of patients in both groups was observed.
      Sarcoidosis was observed most frequently (about in 34% of patients) among
      subjects aged 30-39 years. In group hospitalized in 1996-2000 percent of patients
      aged above 60 has rised (6.8% vs. 2.5%) and percent of patients without clinical
      complaints has significantly decreased (30.5% vs. 50.0% p < 0.05), also percent
      of subjects in II radiological stage has significantly diminished (32.1% vs.
      52.5% p < 0.05). We conclude that during 20 years the profile of hospitalized
      patients with pulmonary sarcoidosis has changed.

PMID- 16989160
TI  - [Systemic mastocytosis].
AB  - Mastocytosis is group of rare disorders characterized by abnormal mast cells
      growth. Pathology of the disease is unknown, mechanisms involved in mast cells
      delineation and growth are considered to play an important role. Unusual and
      broad spectrum of symptoms therefore requires cooperation of different
      specialists. The aim of the study was to assess diagnostic and therapeutic
      methods used in the Gdansk Mastocytosis Centre. 14 patients were studied (9
      adults and 5 children). Bone marrow biopsy was performed in order to assess the
      stage of disease. Pathological, cytological, cytofotometry and genetic
      examination (C-KIT mutation) of the bone marrow were performed. Patients
      suffereing from food allergy and wasp venom anaphylaxis were diagnosed with skin
      prick tests and sIgE. All subjects suffered from urticaria pigmenthosa and
      anaphylaxis. Indolent mastocytosis was diagnosed in six subjects. Patients were
      treated with antihistamines, corticosteroids, cromones and immunotherapy with a
      marked reduction of symptoms. The experience of Gdansk Mastocytosis Centre
      indicates that mastocytosis is a rare and difficult to diagnose disease.

PMID- 16989162
TI  - [Hyperuricaemia in males with obstructive sleep apnoea (osa)].
AB  - Previous studies showed that uric acid (UA) excretion in urine is increased in
      OSA patients and normalized after CPAP therapy. The aim of our study was to
      assess serum UA in a large group of males with OSA before treatment. METHODS: All
      subjects had full or limited PSG, measurements of serum uric acid, cholesterol,
      triglicerydes, glucose levels, lung function tests and medical history for
      cardiovascular diseases. RESULTS: We studied 260 consecutive, obese males (BMI =
      33.1 +/- 6.2 kg/m2), mean age 51.5 +/- 9.9 years, with severe OSA (mean AHI/RDI =
      44 +/- 24, mean overnight SaO2 = 89.2 +/- 5.4%, T90 = 43.8 +/- 34.4%.
      Hyperuricaemia (UA >7 mg%) was found in 56.2% of studied subjects. UA
      concentration correlated with obesity and overnight oxygenation. Multiple
      regression analysis revealed significant correlation between UA and BMI. Subjects
      with hyperuricaemia presented with higher prevalence of systemic hypertension,
      coronary artery disease, diabetes mellitus and COPD. CONCLUSIONS: Hyperuricaemia
      is frequent in males with OSA. Elevated UA levels are related to extreme obesity,
      overnight desaturation and higher prevalence of systemic hypertension, coronary
      artery disease, diabetes and COPD.

PMID- 16989161
TI  - [Cohort analysis for treatment outcomes TB pulmonary cases bacteriologically
      confirmed in Poland].
AB  - In Poland since 1986 system of treatment outcomes monitoring (TOM) of all
      confirmed pulmonary TB (PTB) cases has been introduced. This system is based on
      the Central Tuberculosis Register TB detected and registered in given year from
      the whole network tuberculosis and lung diseases dispensaries in the country--/
      400 disp. in 2004 yr/. The aim of the study was to asses treatment results of PTB
      confirmed cases registered in 2003 and in the period 2001-2003. In 2003 5558
      cases were registered, The treatment outcomes were assessed according to WHO/Euro
      TB-categories after 12 months after start of treatment as PTB: cured--67.8%;
      completed--10.4% (success ratio--77.8%); failed--1.5%, died--5.1% (from TB-
      2.1%); defaulted--7.6%, still on treatment--0.6%; transferred--1.9%. and unknown-
      5.5% all registered PTB cases. In period 2001-2003 proportion patients with
      success of treatment was stable. In 2003 proportion of patients with success of
      treatment was significantly higher in a groups of new cases--83.7 than in
      patients with relapses--73.9%; among women--85.4% than in men--80.9%. Among PTB
      cases smear positive success ratio--81.3 was lower than among PTB cases culture
      positive--84.0. Among patients with diabetes and alcohol abuse the success of
      treatment was significantly lower than more patients without these
      diseases/habit. Alcoholics three times more frequently defaulted treatment than
      patients without this habit. CONCLUSION: The improvement of treatment outcomes is
      impossible without generalize directly observed treatment in all patients in
      continuation phase of treatment.

PMID- 16989163
TI  - [Side effects of specific immunotherapy in patients with hymenoptera venom
      allergy].
AB  - The aim of this study was to estimate safety of specific immunotherapy to
      insects' venom. The frequency of side effects was compared in two groups of
      patients: subjects with hypersensitivity to insects' venom only and patients with
      allergy to other allergens. In the examined group of 32 patients with Hymenoptera
      venoms allergy skin prick tests with common aeroallergens were performed in 30
      subjects. In 18 patients (60%) at least one test was positive. In 23 patients
      (71.9%) immunotherapy with Hymenoptera venom was connected with side effects
      observed just after administration of vaccine. They were mainly local reactions
      (itching, redness and oedema). In 6 patients late reactions were observed. No
      correlation has been found between frequency of side effects of immunotherapy and
      positive results of skin prick tests. However systemic reactions were revealed
      only in the group of patients with at least one positive result of skin prick
      tests.

PMID- 16989164
TI  - [Analysis of prognostic value of TP53 gene mutations in non-small cell lung
      cancer].
AB  - The aim of this study was to assess the frequency and prognostic value of TP53
      gene somatic mutations in non-small cell lung cancer. The study group included
      240 NSCLC patients who underwent pulmonary resection at the Department of
      Thoracic Surgery, Medical University of Gdansk. Tumour samples were evaluated for
      the presence of TP53 gene mutations in exons 5-8. In 157 cases SSCP method was
      used as a screening followed by sequencing of positive samples. In the remaining
      83 patients mutations were analysed by direct sequencing. A total of 76 mutations
      (32%) were found, of those a missense type was dominant (67%), followed by silent
      and null type mutations (14% and 10%, respectively). There was no correlation
      between mutations and clinical characteristics, including age, sex, histological
      subtype, differentiation, tumour size, lymph node metastases, pTNM stage and
      smoking status. A multivariate Cox analysis demonstrated that tumour
      differentiation and pTNM stage were independent prognostic factors, whereas TP53
      gene mutations were not. The results of this study indicate that TP53 gene
      mutations in NSCLC patients are not correlated with clinical characteristics and
      have no impact on survival.

PMID- 16989166
TI  - [Lymphocytic interstitial pneumonia in primary Sjogren syndrome].
AB  - Ljmphocytic interstitial pneumonia (LIP) is a rare form of interstitial
      pneumonia. It can occur as a idiopathic disease however most frequently
      associated with other diseases, particularly Sjogren syndrome. We present a 58
      years old woman, with primary Sjogren syndrome who developed after 7 years
      interstitial lung disease. LIP was diagnosed on the basis of histological
      examinations of specimens obtained by open lung biopsy. Diffuse infiltrations
      composed of small polyclonal lymphocytes, plasma cells with reactive follicules
      were found. Infiltrates observed in bronchial and bronchiolar walls expanded into
      interlobular and alveolar septae. Prednisone in a dose of 40 mg per day was
      introduced and clinical, radiological, spirometric and gasometric improvement was
      observed. The dose of prednisone was gradually reduced but is still continued.

PMID- 16989165
TI  - [The significance of the serum tumour markers as a prognostic and predictor
      factors in nonsmall cell lung cancer patients].
AB  - The aim of the study was to assess the role of serum tumour markers (NSE, Cyfra
      21-1, CEA, LDH, ferritin) as a prognostic and predictive factors in 79 patients
      with advanced NSCLC treated with chemotherapy. Objective response to treatment
      was significantly more frequent in the patient with serum NSE > 12.5 ng/ml.
      Progression of disease was observed more often in patients with serum Cyfra 21-1
      >10 ng/ml or LDH >480 U/L. CEA >3 ng/ml, LDH >480 U/L, for coefficient >1, NSE
      >20 ng/ml and Cyfra 21-1 >10 ng/ml had a negative impact on survival in
      univariate analysis. Independent negative prognostic significance of fer
      coefficient >1 was confirmed by multivariate analysis.

PMID- 16989167
TI  - [Recurrent pneumothorax as alone manifestation of mesothelioma pleurae].
AB  - Malignant mesothelioma of the pleura is a rare neoplasm with a poor prognosis.
      The most often symptoms of this disease are dyspnoe and chest wall pain, which is
      often associated with pleural effusion. We present 35-years old woman with 5
      epizodes of pneumothorax during 3 years (4 of right side and 1-bilateral) in whom
      bilateral pleurodesis was performed. Specimens of lung and pleurae were
      examinated. Result of microscopic and immunohistochemical examination was:
      mesothelioma epithelioides pleurae (mesothelium +, calretyninaa +, EMA+ membrane
      reaction, desmine +/-).

PMID- 16989169
TI  - [Clinical significance of PCNA expression in non-small cell lung cancer].

PMID- 16989168
TI  - [Malignant pleural mesothelioma--histopathological classification, staging and
      microscopic diagnosis].

PMID- 16989170
TI  - [Clinical significance of cyclin Dl expression in non-small cell lung cancer].
AB  - Lung cancer remains interdisciplinary problem. The genetic alterations in non
      small cell lung cancer (NSCLC) are related to tumor suppressor genes and proto
      oncogenes. CCND1 gene, coding cyclin DI, in correlation with pRb is involved in
      regulation of cell cycle arrest in G1 phase. Amplification of CCND1 gene and
      cyclin D1 over-expression was found in several cancers including head and neck
      cancers or colorectal cancer, where these alterations were correlated with worse
      prognosis. The literature addressing the clinical significance of CCND1 gene
      amplification/expression in NSCLC remains poor and prognostic value of these
      alterations in that cancer is still controversial.

PMID- 16989171
TI  - [Lymphocytic interstitial pneumonia].

PMID- 16989172
TI  - [Methods of house dust mites elimination].

PMID- 16989173
TI  - Charge nurses at risk of losing collective bargaining rights.

PMID- 16989174
TI  - Patients and nurses come first.

PMID- 16989175
TI  - Foundation's Workdrugfree helps Oregon businesses prevent workforce substance
      abuse.

PMID- 16989176
TI  - ONA puts HB 2800 hospital nurse staffing law into action.

PMID- 16989177
TI  - National conference brings key message: no safe way to manually lift or move
      patients.

PMID- 16989178
TI  - Mirror, mirror on the wall, what's in my personal care products: a short article
      about 300 million "guinea pigs".

PMID- 16989179
TI  - [Still's disease, adult-onset Still's disease (AOSD)].

PMID- 16989180
TI  - [Autoimmune liver diseases and their overlap syndromes].
AB  - Autoimmune diseases of the liver are chronic inflammatory diseases leading to an
      etiologically undefined immune-mediated attack aimed at the hepatocyte, small
      microscopic bile ducts, and the entire biliary system detectable by
      cholangiography, respectively. From the standpoint of clinical disease three
      entities can be distinguished: autoimmune hepatitis (AIH), primary biliary
      cirrhosis (PBC), and primary sclerosing cholangitis (PSC). These are not only
      different regarding their clinical profile but also differ in diagnostic
      strategy, therapeutic regimen and probability of remission, as well as their
      association with other immune-mediated diseases and cancer. PBC and PSC are
      cholestatic diseases. PBC is most often diagnosed in women. The diagnosis is
      readily reached by the detection of specific antimitochondrial autoantibodies
      directed against pyruvate dehydrogenase (PDH-E2), is associated with an array of
      rheumatological extrahepatic syndromes and responds unsatisfactorily to
      immunosuppressive drugs. Ursodeoxycholic acid leads to biochemical and possibly
      histological benefits. In contrast, PSC affects younger men who suffer from
      inflammatory bowel disease in 75% of cases. PSC is not characterized by specific
      serum autoantibodies. The diagnosis is reached by histology and typical findings
      upon cholangiography. In 10-20% PSC is associated with cholangiocarcinoma and
      also with colon cancer. PSC also does not respond well to immunosuppression.
      Therapeutic interventions include mechanical endoscopic manipulation of the bile
      ducts, treatment of cholangitis and ursodeoxycholic acid. AIH is a classical
      autoimmune disease with a female predisposition, circulating autoantibodies,
      elevated immunoglobulins, the association of other extrahepatic autoimmune
      diseases, and a dramatic response to immunosuppression with normalization of the
      patient's prognosis upon remission and prevention of cirrhosis. However, the
      diagnosis is only reached by the exclusion of other liver diseases also
      characterized by biochemical, histological and clinical features of chronic
      hepatitis. In this light, the precise diagnosis is essential. In spite of the
      clear distinctions of the three diseases overlapping syndromes do exist. These
      can be characterized as the coexistence of serological parameters of PBC and AIH,
      of cholestasis and hepatitis, of autoantibodies and viral markers, or the
      consecutive manifestation of PBC and AIH, or AIH and PSC. However, the overlap of
      genuine autoimmune diseases is rare. This is relevant regarding therapy and must
      lead to the precise clinical and diagnostic discrimination of serological
      autoimmunity (autoantibodies) and genuine autoimmune disease (i.e. AIH) for the
      initiation of efficatious therapeutic measures. AIH, PBC and PSC are well
      established indications for liver transplantation with good results.
      Transplantation is required when cirrhosis is progressive despite therapy and is
      likely to lead to liver failure.

PMID- 16989181
TI  - [Therapy of hepatitis B].
AB  - Worldwide, there are approximately 350 million carriers of hepatitis B virus
      (HBV), of whom half a million to 1 million die from liver disease. The goal of
      treatment is to prevent cirrhosis, hepatic failure, and hepatocellular carcinoma.
      Substantial progress has been made in the treatment for hepatitis B in the past
      decade. Currently approved therapeutic options include interferon alpha,
      lamivudine and adefovir. The efficacy ot the respective antivirals is affected by
      virological and clinical parameters, thus requiring individual treatment
      strategies that will be discussed in detail.

PMID- 16989182
TI  - [Therapy of hepatitis B virus infection].
AB  - In the last years there was a continuous improvement in the therapy of hepatitis
      B virus infection. Meanwhile different therapeutic options are available.
      Therefore the indication for the different treatment options can be chosen
      dependent on clinical, biochemical, virological and histological parameters.
      Therapy with interferon alpha or PEG-interferon alpha should be started if
      positive prognostic parameters and lack of contraindications are present in a
      patient. Especially therapy with PEG-interferon alpha in recent studies showed
      good response rates. As an alternative nucleosides/nucleotides like lamivudine,
      adefovir or entecavir are available. During lamivudine therapy there is an
      increased risk for the selection of resistant strains, while the selection of
      resistant strains is less frequent during the medication of adefovir or
      entecavir. However at present the end of treatment for all
      nucleosides/nucleotides--especially in HBeAg negative patients--is not clearly
      defined. In patients with liver cirrhosis (Child B and C) only nucleos(t)ides
      should be used. In the future combination therapy for the treatment of chronic
      HBV infection seems very attractive. However at present combination therapy is
      not approved yet and therefore these options should only be used in clinical
      studies. Especially, as it seems possible that synergistic, but also antagonistic
      effects may exist between different drugs.

PMID- 16989183
TI  - A chemical look at benzoyl peroxide may prove helpful.

PMID- 16989184
TI  - Monopolar radiofrequency facial tightening: a retrospective analysis of efficacy
      and safety in over 600 treatments.
AB  - BACKGROUND AND OBJECTIVES: Monopolar radiofrequency skin heating coupled with
      cryogen cooling of facial skin for skin tightening has been utilized on over
      10,000 patients since 2002. In order to establish the actual rate and degree of
      side effects in our clinical experience, a retrospective chart review was
      performed. STUDY DESIGN: Charts and clinical images of over 600 consecutive
      patient treatments between May 2002 and June 2006 using a monopolar
      radiofrequency device (Thermacool, Thermage, Haywood, CA) for skin tightening at
      the Maryland Laser, Skin and Vein Institute were retrospectively reviewed. The
      primary presentation for treatment was skin laxity of the lower face. Treatment
      was delivered with a 1-cm2 standard tip at fluences of 81 to 124 J/cm2 (level of
      12.5 to 15), a 1-cm2 "fast" tip at fluences of 62 to 109 J/cm2 (level of 72.0 to
      76.0), a 1.5-cm2 "big fast" tip at fluences of 75 to 130 J/cm2 (level of 61.5 to
      65), and a 3-cm2 "bigger" tip at equivalent fluences as each became available. As
      treatment algorithms evolved over 4 years, the algorithm of multiple passes at
      lower fluence associated with better clinical outcomes and greater patient
      acceptance has been adopted. RESULTS: The most common immediate and expected
      clinical effects were erythema and edema lasting less than 24 hours, although 6
      patients reported edema lasting for up to 1 week. There were no permanent side
      effects. In total, 2.7% of treatments resulted in temporary side effects, the
      most significant of which was a slight depression on the cheek (n = 1), which
      completely resolved within 3.5 months. Other side effects included localized
      areas of acneiform subcutaneous erythematous papules (n = 4) and a linear
      superficial crust (n = 1) with the original tip, all of which resolved within 1
      week. One patient reported small erythematous subcutaneous nodules resolving in
      17 days. Tenderness of the neck lasting from 2 weeks (n = 2) to 3 weeks (n = 1)
      was also reported. CONCLUSIONS: Our data, obtained in an office setting without
      injectable anesthetic or i.v. sedation, indicate that monopolar RF for skin
      tightening is a very safe procedure. The treatment algorithm and tips have
      evolved over several years leading to increased safety and efficacy. Side effects
      are infrequent, self-limited, and minor, comparing favorably to other nonablative
      devices utilized for facial rejuvenation.

PMID- 16989185
TI  - Effect of controlled volumetric tissue heating with radiofrequency on cellulite
      and the subcutaneous tissue of the buttocks and thighs.
AB  - BACKGROUND: Regardless of diet and exercise, genetics plays an important part in
      creating puckering skin or dimples, which are difficult to hide at any age. The
      demand for a nonsurgical, noninvasive treatment of cellulite has inspired some
      manufacturers to invest in a new age of sophisticated devices and treatment
      therapies to repair the skin and improve contours. Although many of these new
      choices have demonstrated a smoothing effect (following a multitude of
      treatments), the objective documentation has in most cases been limited to
      biopsies, circumference measurements, and photographic evidence. HYPOTHESIS: We
      believe that the application of noninvasive high-energy radiofrequency (RF) to
      the skin of the thigh and buttocks heats the subcutaneous adipose tissue, causing
      collagen fibers to contract. The resulting impact to the subcutaneous tissue and
      collagen is expected to improve the skin's external architecture. Given that the
      subcutaneous tissue and adipose tissue are difficult to evaluate through
      histological methods, this investigation seeks to demonstrate the changes that
      occur when applying 2 treatments of high-energy RF on the subcutaneous tissue of
      thighs and buttocks utilizing real-time ultrasound image scanning. MATERIALS AND
      METHODS: Twenty-six healthy female patients (ages 18 to 50) with visible
      bilateral cellulite (grade 1 to 3) on either the buttocks and/or thighs received
      2 treatment sessions (15 days apart) of unipolar RF using the Accent RF System
      (Alma Lasers Inc). The system utilizes a unipolar RF applicator that is
      electrically cooled to aid in patient comfort during the treatment. Appropriate
      energy was set and the treatment was delivered in 3 passes of 30 seconds each.
      Evaluation of the thickness of the subcutaneous tissue on buttocks and thighs
      took place before the first treatment, second treatment, and 15 days following
      the second treatment with a with real-time scanning image ultrasound (Philips
      Medical Systems). Clinical improvement was objectively evaluated through
      comparative pre- and post-treatment measurements of the distance between the
      stratum corneum to the Camper's fascia and from the stratum corneum to the
      muscle. The study also evaluated the structure and changes of the collagen
      (thickening and realignment of septae) resulting from 2 treatments of RE
      Photography was used to document contour and superficial changes. RESULTS: From
      the measurements of the distance between the stratum corneum to the Camper's
      fascia and from the stratum corneum to the muscle we were able to demonstrate
      that 68% of the patients presented a contraction of the volume of approximately
      20%. CONCLUSIONS: Based on the demonstrated results with real-time ultrasound
      scanning, we have observed that 2 RF treatments on the subcutaneous tissue of the
      buttocks and thighs provide a volumetric contraction effect in the majority of
      patients. This validates the primary hypothesis of our protocol and establishes
      that the RF energy works on the connective tissue of the subcutaneous adipose
      tissue. This effect should be the same on any other body part.

PMID- 16989187
TI  - Rhytides, laxity, and photoaging treated with a combination of radiofrequency,
      diode laser, and pulsed light and assessed with a comprehensive grading scale.
AB  - Several classes of nonablative laser and light technologies have been developed
      to target laxity, rhytides, and the various aspects of photoaging. The
      combination of the 3 main classes of nonablative rejuvenation, infrared laser,
      intense pulsed light, and radiofrequency energy, are assessed in the current
      study. Using a comprehensive grading scale developed to evaluate the multiple
      categories of the aging skin, quantitative analysis of changes in each category
      as well as overall improvement and patient satisfaction were calculated. The
      combination technology resulted in a patient mean (95% CI) percent improvement
      per category of 10.9% (8.1% to 13.7%) per treatment and 26% (16.5% to 35.5%)
      overall following a mean (+/- SD) of 2.4 (+/- 1.2) treatments. In addition, the
      patient satisfaction was 71.4%, suggesting that combining nonablative
      technologies may maximize clinical results and patient detection of improvement.

PMID- 16989186
TI  - Hair removal for Fitzpatrick skin types V and VI using light and heat energy
      technology.
AB  - OBJECTIVE: To determine the safety and efficacy of a light and heat energy (LHE)
      based system (SkinStaion system; Radiancy Inc, Orangeburg, NY, USA) for hair
      removal in subjects with skin types V and VI. METHODS: Thirty-one subjects with
      Fitzpatrick skin types V and VI were consented for treatment with the system.
      Twenty-six subjects completed the 12-week follow-up. Safety was evaluated at each
      visit and efficacy was evaluated at both follow-up visits. RESULTS: An average
      hair clearance of 41.7% from 57 treatment sites was reported at the 6-week follow
      up visit and a 35.5% average hair clearance was reported at the 12-week follow
      up. Edema was only reported in 2 cases (7.7%) of the study population. Eleven
      cases of erythema were reported following treatment. CONCLUSION: Treatment with
      the modified LHE system was safe and effective for hair removal in patients with
      skin types V and VI.

PMID- 16989188
TI  - Prospective clinical evaluation of 1440-nm laser delivered by microarray for
      treatment of photoaging and scars.
AB  - BACKGROUND AND OBJECTIVES: The use of thermal heating in microscopic zones is
      generically termed "microrejuvenation." The objective of this study was to
      evaluate the benefits of using a novel 1440-nm Nd:YAG laser (Affirm, Cynosure,
      Westford, MA) with a novel approach for microscopic heating. This device utilizes
      a microarray of lenses delivering a 10-mm beam as hundreds of high-fluence
      beamlets interspersed with a relatively uniform low-fluence background
      irradiation. STUDY DESIGN: Forty subjects (N = 40) at 2 study sites presenting
      with superficial rhytides and other symptoms of photoaging or scars received 3
      treatments at 4-week intervals using a T-250 lens array. Total fluence ranged
      from 3.0 to 7.0 J/cm2. Zimmer air cooling was used for all treatments. No topical
      anesthetic was required. RESULTS: The most common immediate and expected clinical
      effects were erythema and edema lasting less than 24 hours, although 6 patients
      reported edema lasting for up to 1 week. There were no permanent side effects. In
      total, 2.7% of treatments resulted in temporary side effects, the most
      significant of which was a slight depression on the cheek (n = 1), which
      completely resolved within 3.5 months. Other side effects included localized
      areas of acneiform subcutaneous erythematous papules (n = 4) and a linear
      superficial crust (n = 1) with the original tip, all of which resolved within 1
      week. One patient reported small erythematous subcutaneous nodules resolving in
      17 days. Tenderness of the neck lasting from 2 weeks (n = 2) to 3 weeks (n = 1)
      was also reported. RESULTS: In all, 92% of the patients completed 3 treatments.
      Of these, 85% completed the 1-month follow-up. At the follow-up, 94% of subjects
      exhibited improvement in one or more categories, 82% exhibited mild to moderate
      improvement, and 12% exhibited good improvement. Side effects were minimal and
      included mild posttreatment erythema and edema resolving within 24 hours. Pain
      during treatment was judged minimal to moderate. Postauricular histology showed
      areas of thermal injury up to 250 microm deep and 150 microm wide. CONCLUSIONS: A
      1440-nm beam split by a microlens array is a promising new approach for inducing
      nonablative neocollagenesis in the remodeling of scars and rhytids. Histologic
      evidence confirms the microcolumnar nature of collagen heating using this
      microarray.

PMID- 16989189
TI  - Combined 633-nm and 830-nm led treatment of photoaging skin.
AB  - OBJECTIVES: To evaluate the clinical efficacy and ultrastructural changes in
      photodamaged skin after combined 633-nm and 830-nm light-emitting diode (LED)
      treatments. METHODS: Thirty-six subjects received 9 LED treatments over the
      course of 5 weeks and were subsequently evaluated for final clinical improvement
      12 weeks after treatment. Five subjects were also biopsied to determine the
      ultrastuctural posttreatment changes in collagen fibers. RESULTS: A statistically
      significant improvement in wrinkles was seen after profilometric analysis. The
      majority of subjects reported improvements in softness, smoothness, and firmness
      at all time points. Electron microscopic analysis showed evidence of post-LED
      treatment of thicker collagen fibers. CONCLUSIONS: 633-nm and 830-nm LED
      treatments play a role in the treatment of photodamaged skin. LED treatments can
      be used as either a primary or adjunctive treatment modality.

PMID- 16989190
TI  - Nonablative skin resurfacing: the role of PDT.
AB  - As demand for less invasive, highly effective cosmetic procedures grows,
      dermatologists must continue to explore and develop new treatment options.
      Nonablative skin resurfacing techniques offer an effective and noninvasive
      treatment for photorejuvenation. Several studies have shown improvement of
      photodamaged skin and increased collagen production after nonablative treatments
      using vascular lasers, mid-infrared lasers, intense pulsed light, radiofrequency
      devices, fractional resurfacing, and plasma skin rejuvenation. Among the novel
      methods for maximizing the efficacy of nonablative treatment is the concurrent
      use of a photosensitizing agent. The light sources currently most used for
      photodynamic rejuvenation are intense pulsed light and pulsed dye laser. We
      present some preliminary results on rejuvenation using Metvix and red light. We
      are still far from a thorough understanding of the molecular mechanism of
      rejuvenation with this technique, although a nonspecific immune response could be
      involved. Understanding the laser-tissue interactions associated with
      photodynamic therapy is crucial in selecting patients that will most likely
      benefit.

PMID- 16989191
TI  - Photodynamic therapy: practical cosmetic applications.
AB  - Photodynamic therapy (PDT) has been used in the treatment of a variety of benign
      and malignant cutaneous conditions. More recently, it has been used to enhance
      the results of skin rejuvenation procedures. The purpose of this article is to
      review the current practical applications of PDT in a cosmetic practice.

PMID- 16989192
TI  - Multicenter clinical perspectives on a broadband infrared light device for skin
      tightening.
AB  - Modalities for skin tightening include radiofrequency (RF) energy, lasers, and
      combination RF and diode lasers. A new broadband infrared light device (BILD)
      (Titan, Cutera, Inc, Brisbane, CA) targets water to achieve dermal heating and
      collagen remodeling for skin tightening. Although thousands of procedures have
      been performed worldwide with this device, only one article (to the author's
      knowledge) describing its performance in skin tightening has been published.
      Three US dermatologists report their experience with and provide their
      perspective on facial skin tightening with the BILD system. As early adopters,
      they each have 12 to 18 months experience with this system. One author (A.F.T.)
      treated 42 patients twice at 1-month intervals over 18 months. The mean
      improvement score was 1.83 (scale 0 to 4, with 4 denoting maximum improvement)
      with an average follow-up time of 3.7 months. More than 90% of treated patients
      showed visible improvement. No complications were observed and patient
      satisfaction was high. This paper presents the general consensus of the authors
      on patient selection and treatment protocol, their modifications of the
      manufacturer's treatment protocol, and the outcomes of 42 patients treated by one
      author (A.F.T.). The observations were gathered separately and turned out to be
      very similar. The recommendations are presented to help practitioners achieve
      consistently good results and avoid complications with the BILD procedure.

PMID- 16989193
TI  - Use of antibiotics in dermatologic surgery.
AB  - When skin integrity is disrupted during a surgical procedure, its protective
      barrier becomes compromised and predisposes the individual to cutaneous
      infection. Postoperative infection remains a considerable cause of morbidity and
      mortality. This article briefly reviews the etiology and management of
      postoperative infections following dermatologic surgery.

PMID- 16989194
TI  - Treatment considerations for inflammatory acne: clinical evidence for adapalene
      0.1% in combination therapies.
AB  - Acne vulgaris is an exceptionally common, chronic, and recurring disease. It
      involves multiple etiological factors including follicular hyperkeratinization,
      increased sebum production, Propionibacterium acnes proliferation, and
      inflammation. Presently, oral isotretinoin is the only single agent that is
      effective against all 4 major pathophysiologic features. However, this drug is
      also responsible for several serious side effects, including teratogenicity.
      Therefore, it should be used in only the most severe cases and alternative
      treatment approaches for inflammatory acne, such as initial combination therapy,
      should be considered first. Combination therapy in inflammatory acne
      simultaneously targets multiple pathogenic factors. Current guidelines recommend
      early initiation of combination therapy with a topical retinoid and
      antimicrobials for mild to moderate inflammatory acne and topical retinoids with
      oral antibiotics (with or without the use of benzoyl peroxide) for moderate to
      severe cases of acne, followed by maintenance therapy with topical retinoids.
      This review evaluates the rationale and clinical evidence for the use of
      adapalene in combination therapy for inflammatory acne.

PMID- 16989196
TI  - Development of a keratoacanthoma after topical photodynamic therapy with 5
      aminolevulinic acid.
AB  - Since its FDA approval in 1999, photodynamic therapy (PDT) with topical 5
      aminolevulinic acid has become an increasingly popular modality for the treatment
      of actinic keratosis (AKs). It is hoped that in addition to improving clinical
      signs and symptoms of AKs, PDT might prevent the development of skin cancer. We
      present a case of a patient developing a keratoacanthoma immediately following
      PDT for AKs.

PMID- 16989195
TI  - A novel skin cream containing a mixture of human growth factors and cytokines for
      the treatment of adverse events associated with photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) with topical 5
      aminolevulinic acid (ALA) is becoming a more popular dermatologic procedure.
      Newer protocols have virtually eliminated any associated untoward effects.
      Phototoxicity, although rare, can still occur and requires aggressive post
      therapy care. Recently, a new biorestorative skin care cream, containing human
      growth factors and cytokines, was used to treat 2 severe cases of PDT-associated
      phototoxicity. MATERIALS AND METHODS: This paper describes 2 case reports of
      severe phototoxicity following ALA-PDT treatments. The novel skin care cream was
      utilized in both cases phototoxicity. RESULTS: Complete resolution of the
      phototoxic reaction was seen, leaving both patients with normal skin texture and
      tone. CONCLUSIONS: This novel skin care cream may prove useful in wound healing
      following treatment with lasers and light sources or dermatologic surgery.

PMID- 16989197
TI  - A quantitative and comprehensive grading scale for rhytides, laxity, and
      photoaging.

PMID- 16989198
TI  - [Resonance phenomena and their role in physiotherapy].

PMID- 16989199
TI  - [Tablet radon preparations].

PMID- 16989200
TI  - [Radon alpha-applicator in therapy of reactive and inflammatory arthropathies].
AB  - The article presents the results of treatment of 42 patients with reactive and
      inflammatory arthropathy of the knee and ankle joints. Nineteen patients were
      exposed to EHF (460 MHz) electromagnetic field, 23 patients received local
      cutaneous alpha therapy with radon applicator. Radon concentration was 7.4 Bq/l
      (0.2 nCi/l), the exposure was 90 minutes. Local alpha-therapy by radon applicator
      proved highly active as shown by attenuation of inflammation, excudative and
      proliferative disorders in the joints.

PMID- 16989201
TI  - [Updated assessment of efficacy of dry air radon baths of different
      concentrations at the stage of medical rehabilitation of patients with bronchial
      asthma].
AB  - We studied effects of dry air radon baths (DARB) on bronchial hypersensitivity
      and serum levels of proinflammatory cytokines in patients with bronchial asthma
      (BA) with reference to the disease severity and radon therapy regimen. DARB with
      radon concentrations 40 nCi/l significantly raise the threshold of bronchial
      sensitivity to metacholine compared to control and DARB with radon concentration
      20 nCi/l. The effect was the highest in patients with mild asthma. Comparison of
      serum levels of alpha- and gamma-interferons, tumor necrosis factor alpha, IL-2,
      IL-4 and IL-6 has shown that alpha radon radiation significantly increases serum
      gamma-interferon and reduces IL-4 concentration. These changes were more evident
      in the group with high radon content. Thus, radon therapy has immunomodulating
      activity.

PMID- 16989202
TI  - [Mechanisms of correcting action of speleotherapy on cardiorespiratory system of
      patients suffering from chronic obstructive bronchitis].

PMID- 16989203
TI  - [Oral intake of mineral water and activity of NO-synthase in hepatic and
      gastrictissues of eperimental animals].

PMID- 16989204
TI  - [Low temperature peloid therapy for sanatorium treatment of biliary dyskinesia].

PMID- 16989205
TI  - [Efficacy of SMC-electrophoresis of peat mud in primary chronic duodenitis].
AB  - Sinusoidal modulated current (SMC) electrophoresis of peat mud was used as
      monotherapy of primary chronic duodenitis in Uva sanatorium. A total of 65
      patients with primary chronic duodenitis received SMC electrophoresis of peat mud
      diluted with distilled water. The effect was followed up with
      fibrogastroduodenoscopy and target biopsy of duodenal mucosa with further study
      of its morphological structure and element composition, acid-producing function
      of the stomach, hormonal profile, collagen metabolism. Positive changes were
      observed in clinical-endoscopic and morphological picture of the disease which is
      explained by favourable shifts in hormonal status and normalization of collagen
      metabolism in duodenal mucosa.

PMID- 16989206
TI  - [Therapeutic exercise complex in varicose small pelvis veins in women].

PMID- 16989207
TI  - [Statodynamic loads effects on parameters of cardiovascular system in healthy
      women aged 35-50 years].

PMID- 16989208
TI  - [Introduction of new prophylactic technologies at Nalchik health resort].
AB  - The introduction of educational programs on prevention of cardiovascular
      disorders at Nalchik health resort and the experience obtained show that
      correction of cardiovascular disease risk factors according to the educational
      programs consolidates positive results of complex sanatorium treatment, reduces
      risk factors level and promotes compliance of the patients to healthy life style.

PMID- 16989209
TI  - [Physiomodified cell therapy: experimental and clinical grounds for further
      development].

PMID- 16989210
TI  - [Vapor-phase extraction of organic substances in the study of mineral waters].

PMID- 16989211
TI  - [Conditioning of therapeutic muds in their packing].

PMID- 16989212
TI  - [Use of natural therapeutic factors in the treatment, rehabilitation and
      prophylaxis of gynecological diseases out of health resort].

PMID- 16989213
TI  - [Therapeutic exercise in chronic cardiac failure].

PMID- 16989214
TI  - [Interval hypoxic training as a method of prophylaxis of meteopathic reactions in
      patients with bronchial asthma: guide for physicians].

PMID- 16989215
TI  - [Structural analysis of the information value of lung ventilation parameters for
      assessment of bronchodilation response in patients with bronchial asthma].
AB  - The goal of this work was to perform structural analysis of the information value
      of lung ventilation parameters for assessment of bronchodilation response in
      patients with bronchial asthma. The information value of lung ventilation
      parameters is considered as a function of the initial level of ventilation
      disorders and the method of calculation of bronchodilation response. Structural
      analysis revealed that different lung ventilation parameters have different
      information value for assessment of bronchodilation response in patients with
      bronchial asthma. The effect of the method of calculation and the initial
      severity of ventilation disorders on the information value of lung ventilation
      parameters is also rather complex. Parameters with maximal information value for
      analysis of the results of broncholytic tests in patients with bronchial asthma
      are determined. These parameters have high information value independently of the
      method of calculation.

PMID- 16989216
TI  - [A system of electrode arrangement for measurement of the coordinates of sources
      in the myocardium area].
AB  - A system of electrode arrangement for localization of zones of small
      depolarization abnormalities in human myocardium is suggested. Standard
      electrodes R, L, F and Frank electrodes H, M compatible with standard methods of
      examination. The total number of electrodes in the system is 15. A technique for
      reconstruction of the coordinates and orientation angles of the abnormality
      sources from measured electrode potentials is suggested. Statistical modeling is
      used to assess the dependence of the reconstruction error on the source position
      and orientation. The maximal error of coordinate measurement is found to be
      approximately 1.5 mm; average error, 0.75 mm.

PMID- 16989217
TI  - [Mathematical modeling of cardiovascular system in patients with hemorrhage and
      hypothermia].
AB  - Mathematical modeling is the most expedient method for studying the response of
      human cardiovascular system to a combined effect of several external factors, in
      particular, hemorrhage and hypothermia. A complex mathematical model integrating
      models of the functional systems of human body and the physiological effects of
      disturbing factors can be used to study the combined effect of external factors.
      It allows the response of human body to various combinations of external effects
      of different intensities to be assessed with high accuracy. In addition, the
      model makes it possible to prognosticate the dynamics of changes in the
      cardiovascular system parameters from their initial variation. This facilitates
      prediction of the development of patient's state.

PMID- 16989218
TI  - [Ionization chambers with preamplifiers for X-ray exposure metering systems].
AB  - Ionization chambers with preamplifiers available from SpektrAp, Ltd., are
      described. The ionization chambers are intended for use in X-ray automatic
      exposure systems of diagnostic X-ray apparatuses. The ionization chambers provide
      automated matching of their sensitivity to the sensitivity of modern intensifying
      screens. The preamplifier provides direct integration of the ionization chamber
      current. It can operate within the entire dose rate range of the roentgenographic
      mode and meets the requirements of modern diagnostic X-ray detectors to the dose
      range. Special techniques for increasing the noise immunity of preamplifiers are
      described. Performance specifications of the ionization chambers and
      preamplifiers are given.

PMID- 16989219
TI  - [Experimental determination of radiation scattering and absorption coefficients
      in a homogeneous layer of highly-dispersive biological medium].
AB  - A method for experimental determination of optical characteristics of a highly
      dispersive medium (radiation scattering and absorption coefficients) is
      described. The method is based on two mathematical models of ultrashort laser
      pulse propagation through a highly-dispersive medium (HDM), an axial model and a
      diffusion model. Milk dissolved in water was used as HDM. Dependences of optical
      characteristics of HDM on the concentration of milk in water are obtained. The
      limits of applicability of the axial and diffusion models to media with different
      scattering and absorption characteristics are determined.

PMID- 16989220
TI  - [Scattered X-ray radiation in diagnosis of mammary gland diseases].
AB  - The possibility of estimating the effective atomic number distribution from the
      ratio of the scattering and total absorption coefficients is considered. To
      illustrate the use of this technique in mammology, the results of measurement of
      microcalcinate and cholesterol distribution are discussed. It is suggested that
      tomographic examination of mammary gland should include detection of scattered
      radiation.

PMID- 16989221
TI  - [A method for calculation of the absorbed dose].
AB  - The method suggested in this work uses spectral dependences of X-ray radiation
      intensity. The obtained theoretical dependences of attenuation factors coincide
      with the experimental values with an accuracy of 1-3%. The suggested technique
      makes it possible to determine the absorbed and exposure doses of radiation. It
      also provides determination of contrast of a shadow X-ray image.

PMID- 16989222
TI  - [An algorithm for synthesis of small-size autonomous devices for detection of
      medico-biological parameters].
AB  - Problems of synthesis of devices for detection of medico-biological parameters
      are considered. A classification of the devices and their functional units is
      proposed. An algorithm for synthesis of detectors of medico-biological parameters
      on the basis of multiple-use functional units is suggested. The algorithm is
      based on analysis of functional unit modifications providing optimization of the
      device characteristics.

PMID- 16989223
TI  - [An approach to decreasing the dose load in prophylactic X-ray examination].
AB  - The concept of small radiation dose is uncertain. Usually, doses below 300 mSv
      are considered as small. In this work, a mathematical approach is used to
      consider changes in peripheral blood count caused by exposure to an effective
      dose below 1 mSv. The ACS-ENOFIT device is used to assess the efficiency of
      treatment of a number of diseases. The results obtained in this work show that an
      analytical method should be used for determination of the dose value and
      monitoring of changes in the systems of human body.

PMID- 16989224
TI  - [Problems of development of a uniform nomenclature of medical goods].
AB  - Problems of development of a uniform nomenclature of medical goods are
      considered. The importance of compliance of the developed uniform nomenclature
      with numerous existing standards is emphasized. The uniform nomenclature should
      also be approved by administrative institutions in the field of medicine.

PMID- 16989225
TI  - [An automated microscopy system MECOS-Ts2 and its trial use for blood and bone
      marrow smear analysis].
AB  - Disadvantages of conventional procedures for testing of medical automated
      microscopy systems are considered. A testing procedure based on step-by-step
      testing of the system units is suggested. The procedure makes use of remote data
      analysis through communication lines. The structure of MECOS-Ts2 automated
      microscopy system and the procedure for its testing are considered.

PMID- 16989226
TI  - [Use of ACS-ENOFIT system for mass-scale examinations].
AB  - Typical procedures for introduction of the ACS-ENOFIT system into use in medical
      institutions are considered. The ACS-ENOFIT system can be used for health status
      monitoring on the basis of analysis of standard peripheral blood count.

PMID- 16989227
TI  - [Experience in the use of equipment for ECG system analysis in municipal
      polyclinics].
AB  - Two electrocardiographs, an analog-digital electrocardiograph with preliminary
      analog filtering of signal and a smart cardiograph implemented as a PC-compatible
      device without preliminary analog filtering, are considered. Advantages and
      disadvantages of ECG systems based on artificial intelligence are discussed. ECG
      interpretation modes provided by the two electrocardiographs are considered. The
      reliability of automatic ECG interpretation is assessed. Problems of rational use
      of automated ECG processing systems are discussed.

PMID- 16989233
TI  - [Blood glucose self-monitoring in diabetics needs constant support by nurses].

PMID- 16989234
TI  - [Caring so as to heal oneself?].

PMID- 16989235
TI  - [When a wound gets infected...what can the nurse do?].

PMID- 16989236
TI  - [The nursing consultation, an advance for the profession].

PMID- 16989237
TI  - [Nursing consultation and evolution of the profession].

PMID- 16989238
TI  - [Nursing consultation, a new role to invest in the clinical nursing field].

PMID- 16989239
TI  - [Therapeutic education, a process that is necessarily "plural"].

PMID- 16989240
TI  - [Therapeutic care of patients with HIV].

PMID- 16989242
TI  - [How to facilitate the first participation in the education program after the
      prescription of the base treatment?].

PMID- 16989241
TI  - [MOTIV-SEP, an educational program for patients with multiple sclerosis].

PMID- 16989243
TI  - [The nursing consultation after the disclosure announcement of cancer].

PMID- 16989245
TI  - [The nursing consultation, what reality for community nurses?].

PMID- 16989244
TI  - [Measurement of the activity of a consultation in stoma care].

PMID- 16989246
TI  - [Education of the diabetic patient at home].

PMID- 16989247
TI  - [The nursing consultation].

PMID- 16989248
TI  - [The nursing consultation, challenges and perspectives for the profession].

PMID- 16989249
TI  - Cultural competence of baccalaureate nursing faculty: are we up to the task?
AB  - Reported low levels of cultural competence among baccalaureate nursing students,
      as well as professional nurses, have raised questions about nursing faculty's
      readiness to prepare culturally competent graduates. This study examined cultural
      competence among faculty of baccalaureate nursing programs in Louisiana. Using a
      five-point Likert-type scale, the respondents were asked to express their level
      of agreement with statements addressing the components of cultural competence.
      The data analysis revealed the respondents' rating of their cultural awareness
      (4.14), desire (3.67) knowledge (3.65), skills (3.65), and encounters (3.56).
      Overall cultural competence was rated as 3.73. When the overall cultural
      competence index was regressed on the index of each subscale, the cultural
      knowledge index and the cultural encounter index significantly explained 87% of
      the variance in the model. These findings suggest that faculty should be
      encouraged to attend continuing education programs on cultural competence to
      improve their knowledge in this area. This continuing education, coupled with
      more local and/or international cross-cultural encounters should significantly
      improve the overall cultural competence of the respondents.

PMID- 16989250
TI  - "Can we talk?" Using critical self-reflection and dialogue to build diversity and
      change organizational culture in nursing schools.
AB  - Nursing is often cited as a homogenous profession composed of a predominance of
      white females. It is sometimes posited that this homogeneity might be a
      contributor to the disparity of nursing care available to minority populations
      (Blakeney, 2002; Leininger, 1991). Today's nursing students do not mirror the
      nation's population as only 12.3% of RNs represent racial or ethnic minority
      groups (AACN, 2001). The absence of sufficiently diverse students in nursing
      schools, may have led to a dearth of qualified providers in underrepresented
      neighborhoods. Building diversity in nursing schools prepared specifically to
      reduce health disparities is, and will continue to be a challenge. While, some
      schools are beginning to yield successful returns, many are still searching for
      answers. The answer is not as simple as "increasing the numbers" or sending
      people to training seminars or conferences. This article focuses on what the
      author believes to be a preliminary and critical step to begin an effective and
      successful diversity initiative--critical self-reflection and dialogue. This
      involves the examination and deconstruction of old paradigms, assumptions, and
      prejudices, individually and collectively held and the construction of space,
      respect, and humility to discuss self in relation to "other."

PMID- 16989251
TI  - Prayer: folk home remedy vs. spiritual practice.
AB  - A multidisciplinary review of the literature reveals that prayer, in a
      multicultural context, may be viewed as both a folk home remedy and a practice of
      spirituality. Understanding cultural differences and similarities of the use of
      prayer as a variable for health promotion may have implications for tailoring
      treatment approaches to eliminate disparities in providing care to clients of
      diverse cultural backgrounds. This paper presents these similarities and
      differences within the cultural beliefs of the White, African-American, and
      Hispanic populations.

PMID- 16989252
TI  - Diabetes lay educator case study: one woman's experience working with the
      Hispanic migrant and seasonal farmworkers.
AB  - In the year 2000, Migrant Health Services, Inc. began utilizing Diabetes Lay
      Educators (DLEs) as a way to improve the health status of Hispanic migrant
      farmworkers with diabetes. The purpose of this case study was to provide insight
      into the perceptions of one DLE and characteristics she needed to achieve
      positive client outcomes. These characteristics included a strong internal desire
      to help this population, a knowledge base, and advocacy skills needed to work
      between two cultures.

PMID- 16989253
TI  - An educator's perspective on the emerging Cuba and multiculturalism.
AB  - Plagued by many years of frequent leadership changes, and influences from power
      brokers whose policies and politics were oftentimes detrimental to Cuba's
      emerging as an industrialized and diverse economy nation, Cuba is now attempting
      to move beyond the survival mode. After the symbiotic relationship between the
      Soviet Union was dismantled in the 90s, Cuba is now undergoing metamorphoses of
      growth and change, socially, politically and culturally, while still remaining a
      mixture of worlds both rural and urban. This narrative article describes the
      multicultural experiences that an American university professor recently
      experienced while visiting Cuba.

PMID- 16989254
TI  - Psychometric examination of the Daily Spiritual experiences Scale.
AB  - Despite the burgeoning research literature addressing spirituality and its
      measurements, few instruments have undergone rigorous reliability and validity
      testing. This study contributed to determining the reliability and validity of
      the 16- and 6-item Daily Spiritual Experiences Scale (DSES) in a convenience
      sample of African Americans ages 34-85. Data were collected via self-administered
      questionnaire including the DSES and sociodemographic variables thought to
      influence spiritual experiences. Data were analyzed using paired t-tests, ANOVA,
      inter-class correlation coefficients, Pearson's correlation, and Cronbach's
      alpha. Both versions were stable over time, internally consistent, and the forms
      were equivalent and valid in an all-African American sample.

PMID- 16989255
TI  - How language barriers impact patient care: a commentary.
AB  - The population of the United States population is growing more diverse at a rapid
      rate through the 21st century. Health care providers are interacting more
      frequently with patients of diverse ethnic affiliations where health beliefs,
      languages, and life experiences may differ greatly from their own. According to
      Timmins (2002), "...the U.S. health care system is largely geared toward serving
      English speakers." This is because language is the most common barrier in any
      health care setting and has been found to be a risk factor with adverse outcomes.
      Health care providers and patient communication are positively correlated with
      improved health outcome. Health outcomes include medication regimen, preventive
      testing, and patient satisfaction.

PMID- 16989256
TI  - Established bioprocesses for producing antibodies as a basis for future planning.
AB  - In the early years of monoclonal antibody production for human therapy and
      diagnosis the methods used were arrived at by individual organisations. However,
      there is now an accumulating body of information on antibodies and fragments that
      have been produced by processes approved for human use. This information is
      becoming available at a time when the number of potential antibody-based
      medicines is growing sharply. The review addresses the reported production
      routes, their scale and the titres achieved. It identifies the performances of
      fed-batch and perfusion culture versus batch culture, and compares processes for
      the production of antibodies for diagnosis and for antibody fragments. The
      analysis defines the likely routes of future production in a sector where
      demanding regulations constrain new technology. It also indicates what levels of
      performance new approaches will need to meet to be competitive.

PMID- 16989257
TI  - Fedbatch culture and dynamic nutrient feeding.
AB  - In the past decade, we have seen a rapid expansion in mammalian cell based
      therapeutic proteins reaching clinical applications. This increased demand has
      been met with much increased productivity through intensive process development.
      During this time, fedbatch culture processes have emerged as the predominant mode
      for producing recombinant proteins. In this review, we discuss the fundamentals
      of fedbatch culture process design, focusing on the use of stoichiometric
      nutrient requirements for feed medium formulation, and articulating the need and
      potential means for devising rational dynamic feeding schemes. Incorporation of
      on-line nutrient measurement will play a key role in further refinement of
      process control for the development of a much sought after generic feeding
      strategy that can respond to the changing demands of different cell lines in a
      fluctuating culture environment. The future of process engineering will likely
      require a combination of current process engineering strategies along with a
      better understanding and control over cell physiology. Process development will
      likely to entail not only optimizing traditional engineering parameters but also
      engineering cell lines with desired characteristics. The integration of cell
      engineering and process intensification will likely provide the stimuli that
      propel the limits of growth and productivity to the next high level.

PMID- 16989258
TI  - The "push-to-low" approach for optimization of high-density perfusion cultures of
      animal cells.
AB  - High product titer is considered a strategic advantage of fed-batch over
      perfusion cultivation mode. The titer difference has been experimentally
      demonstrated and reported in the literature. However, the related theoretical
      aspects and strategies for optimization of perfusion processes with respect to
      their fed-batch counterparts have not been thoroughly explored. The present paper
      introduces a unified framework for comparison of fed-batch and perfusion
      cultures, and proposes directions for improvement of the latter. The comparison
      is based on the concept of "equivalent specific perfusion rate", a variable that
      conveniently bridges various cultivation modes. The analysis shows that
      development of economically competitive perfusion processes for production of
      stable proteins depends on our ability to dramatically reduce the dilution rate
      while keeping high cell density, i.e., operating at low specific perfusion rates.
      Under these conditions, titer increases significantly, approaching the range of
      fed-batch titers. However, as dilution rate is decreased, a limit is reached
      below which performance declines due to poor growth and viability, specific
      productivity, or product instability. To overcome these limitations, a strategy
      referred to as "push-to-low" optimization has been developed. This approach
      involves an iterative stepwise decrease of the specific perfusion rate, and is
      most suitable for production of stable proteins where increased residence time
      does not compromise apparent specific productivity or product quality. The push
      to-low approach was successfully applied to the production of monoclonal antibody
      against tumor necrosis factor (TNF). The experimental results followed closely
      the theoretical prediction, providing a multifold increase in titer. Despite the
      medium improvement, reduction of the specific growth rate along with increased
      apoptosis was observed at low specific perfusion rates. This phenomenon could not
      be explained with limitation or inhibition by the known nutrients and
      metabolites. Even further improvement would be possible if the cause of apoptosis
      were understood. In general, a strategic target in the optimization of perfusion
      processes should be the decrease of the cell-specific perfusion rate to below
      0.05 nL/cell/day, resulting in high, batch-like titers. The potential for high
      titer, combined with high volumetric productivity, stable performance over many
      months, and superior product/harvest quality, make perfusion processes an
      attractive alternative to fed-batch production, even in the case of stable
      proteins.

PMID- 16989259
TI  - Towards industrial application of quasi real-time metabolic flux analysis for
      mammalian cell culture.
AB  - Cellular physiology and metabolism were monitored using a quasi real-time
      combination of on-line and off-line data to estimate metabolic fluxes in an
      established bioreaction network. The utility of this approach towards optimizing
      bioreactor operation was demonstrated for CHO cells cultivated in 15 L perfusion
      reactors at 20 x 10(6) cells/mL. Medium composition and dilution rates were
      changed to obtain several steady states with varying glucose and glutamine
      concentrations. When cells were restored to initial culture medium and perfusion
      rate conditions after being exposed to lower glucose and glutamine
      concentrations, the pyruvate flux into the TCA cycle was increased 30% while the
      pyruvate flux through lactate was decreased 30%, suggesting steady-state
      multiplicity. By appropriately altering cellular metabolism, perfusion
      bioreactors can operate at lower perfusion rates without significant accumulation
      of inhibitory metabolites such as lactate. Changes in glucose, lactate and
      glutamine uptake/production rates had significant effects on the calculation of
      other fluxes in the network. Sensitivity analysis of these key metabolic fluxes
      highlighted the need for accurate and reliable real-time sensors. Overall, rapid
      observation of metabolic fluxes can be a valuable tool for bioprocess
      development, monitoring and control. The framework presented in this study offers
      a convenient means for quasi real-time estimation of metabolic fluxes and
      represents a step towards realizing the potential of metabolic flux analysis for
      accelerated bioprocess optimization.

PMID- 16989260
TI  - Engineering cells for cell culture bioprocessing--physiological fundamentals.
AB  - In the past decade, we have witnessed a tremendous increase in the number of
      mammalian cell-derived therapeutic proteins with clinical applications. The
      success of making these life-saving biologics available to the public is partly
      due to engineering efforts to enhance process efficiency. To further improve
      productivity, much effort has been devoted to developing metabolically engineered
      producing cells, which possess characteristics favorable for large-scale
      bioprocessing. In this article we discuss the fundamental physiological basis for
      cell engineering. Different facets of cellular mechanisms, including metabolism,
      protein processing, and the balancing pathways of cell growth and apoptosis,
      contribute to the complex traits of favorable growth and production
      characteristics. We present our assessment of the current state of the art by
      surveying efforts that have already been undertaken in engineering cells for a
      more robust process. The concept of physiological homeostasis as a key
      determinant and its implications on cell engineering is emphasized. Integrating
      the physiological perspective with cell culture engineering will facilitate
      attainment of dream cells with superlative characteristics.

PMID- 16989261
TI  - Mass vaccination: when and why.
AB  - With increased demand for smallpox vaccination during the nineteenth century,
      vaccination days--early mass vaccination campaigns--were conducted over time
      limited periods to rapidly and efficiently protect maximum numbers of susceptible
      persons. Two centuries later, the challenge to rapidly and efficiently protect
      populations by mass vaccintion continues, despite the strengthening of routine
      immunization services in many countries through the Expanded Programme on
      Immunization strategies and GAVI support. Perhaps the most widely accepted reason
      for mass vaccination is to rapidly increase population (herd) immunity in the
      setting of an existing or potential outbreak, thereby limiting the morbidity and
      mortality that might result, especially when there has been no routine
      vaccination, or because populations have been displaced and routine immunization
      services disrupted. A second important use of mass vaccination is to accelerate
      disease control to rapidly increase coverage with a new vaccine at the time of
      its introduction into routine immunization programmes, and to attain the herd
      immunity levels required to meet international targets for eradication and
      mortality reduction. In the twenty-first century, mass vaccination and routine
      immunization remain a necessary alliance for attaining both national and
      international goals in the control of vaccine preventable disease.

PMID- 16989262
TI  - Mass vaccination and surveillance/containment in the eradication of smallpox.
AB  - The Smallpox Eradication Program, initiated by the WHO in 1966, was originally
      based on mass vaccination. The program emphasized surveillance from the
      beginning, largely to track the success of the program and further our
      understanding of the epidemiology of the disease. Early observations in West
      Africa, bolstered by later data from Indonesia and the Asian subcontinent, showed
      that smallpox did not spread rapidly, and outbreaks could be quickly controlled
      by isolation of patients and vaccination of their contacts. Contacts were usually
      easy to find because transmission of smallpox usually required prolonged face-to
      face contact. The emphasis therefore shifted to active searches to find cases,
      coupled with contact tracing, rigorous isolation of patients, and vaccination and
      surveillance of contacts to contain outbreaks. This shift away from mass
      vaccination resulted in an acceleration of the program's success.

PMID- 16989263
TI  - Mass immunization programs: principles and standards.
AB  - Mass immunization involves delivering immunizations to a large number of people
      at one or more locations in a short interval of time. Good mass immunization
      programs apply planning and quality standards that maximize return on resources
      invested and provide the greatest individual benefits when immunizing many people
      in a short period of time. These programs can be used to counter contagious
      outbreaks, adopted as a repeated means of sustained healthcare delivery, or
      applied where many people move through a specific place in a short interval of
      time. Relevant quality standards address appropriate facilities and supplies,
      training of professional and paraprofessional staff, education of potential
      vaccinees and methods to screen them for contraindications to immunization,
      safeguards against anaphylaxis and syncope, documentation, safety surveillance,
      and a quality-improvement program. Successful mass immunization programs require
      early planning that builds on existing competencies. As the number of available
      vaccines increases, prioritizing which vaccines to administer during mass
      campaigns requires consideration of effectiveness, safety, and a cost-benefit
      equation from both the individual and community perspectives. Mass immunization
      campaigns aim to maximize the health of a population, but such campaigns need to
      be customized based on individual contraindications to immunization. Mass
      immunization programs need to be conducted ethically, with considerations of
      benefit versus risk and the need for detailed education of healthcare workers and
      vaccinees.

PMID- 16989264
TI  - Immunization campaigns in the UK.
AB  - A mass immunization campaign is a rapid vaccination intervention across age
      groups as opposed to provision through routine vaccination at a specified age
      attainment. Some countries use campaigns routinely as they have experience that
      shows that in their health systems higher coverage can be reached through
      campaigns than by routine service provision. Whilst many industrialized and non
      industrialized countries have introduced new vaccines into their routine
      programme, the UK is unusual in deliberately doing this via campaigns. A number
      of mass immunization campaigns have been implemented in the UK, either integrated
      into the routine immunization programme such as the annual influenza immunization
      campaign; as a catch-up campaign alongside the introduction of a new vaccine into
      the routine vaccination schedule (MMR, Haemophilus influenzae b, Meningococcal C
      conjugate vaccine); or as a one-off campaign, to boost immunity in a particular
      age group, without introducing the vaccination into the schedule routinely at
      that age (Haemophilus influenzae b). Campaigns require intense planning at
      national and local level with leadership to achieve proper management. Although
      the components of an immunization campaign can be described separately--strategic
      planning, vaccine supply, communication and surveillance; for a programme to be
      successful integrated planning is essential.

PMID- 16989265
TI  - Diphtheria.
AB  - Diphtheria is a contagious upper respiratory illness that was a major cause of
      childhood mortality in the prevaccine era. In the early twentieth century, an
      effective toxoid vaccine was developed. Implementation of childhood vaccination
      virtually eliminated diphtheria from developed countries after the Second World
      War and implementation of the Expanded Program on Immunization in developing
      countries led to rapid declines in diphtheria globally in the 1980s. However, in
      the 1990s, a massive epidemic of diphtheria spread throughout the countries of
      the former Soviet Union. Unlike the prevaccine era, most cases of severe disease
      and deaths were reported among adults. Multiple factors contributed to the
      epidemic, including increased susceptibility among both adults and children;
      suboptimal socioeconomic conditions; high population movement; and delay in
      implementing appropriate control measures. Mass immunization was the key element
      in the epidemic control strategy developed and implemented in a well-coordinated
      response by an international public health coalition. This strategy focused on
      rapidly raising population immunity of both adults and children; the immunization
      of more than 140,000,000 adults and adolescents and millions of children
      successfully controlled the epidemic. While improved coverage of children in
      developing countries with diphtheria toxoid has led to progressive decreases in
      diphtheria; eradication is unlikely in the foreseeable future and gaps in
      immunity among adult population exist or are developing in many other countries.
      Routine childhood immunization with diphtheria toxoid is the key to controlling
      diphtheria while the role of routine adult reimmunization is less established;
      mass immunization will remain an important control measure for widespread
      diphtheria outbreaks.

PMID- 16989266
TI  - Universal mass vaccination against hepatitis A.
AB  - When first introduced in 1992 the hepatitis A vaccine was recommended for
      individuals at high risk of exposure. This policy was not expected to have a
      significant impact on disease incidence at population level in view of the
      epidemiology of the hepatitis A virus (HAV). More recently two countries, Israel
      and Bahrain, and regions or subpopulations in others (Australia, China,
      Byelorussia, Italy, Spain, US) have embarked upon more ambitious vaccination
      programmes that aim to immunize whole birth cohorts. After a brief survey of the
      virology and epidemiology of HAV, the disease burden it inflicts and a short
      history of the development of HAV vaccines--both live (in China) and killed
      vaccines are available--he vaccination programmes introduced in the countries
      mentioned above are described. The results have been spectacular: disease
      incidence, not only in the vaccinated cohorts but also in the whole population,
      have plummeted within a few years of the start of mass vaccination. There is now
      convincing evidence that the vaccine confers herd immunity if the main spreaders
      of the virus are targeted for immunization. This finding should encourage other
      countries to start mass vaccination programmes against HAV, particularly as
      pharmacoeconomic studies are beginning to show that such a strategy could be a
      cost-effective way of controlling the disease. It is now even conceivable to
      eradicate HAV. In fact, this should be easier to achieve than polio eradication
      as HAV vaccines confer more durable immunity than polio vaccines. However, the
      global disease burden of HAV is generally thought not to be high enough to
      justify such an undertaking in the foreseeable future.

PMID- 16989267
TI  - Mass vaccination against hepatitis B: the French example.
AB  - Mainland France is considered as a low endemicity area for hepatitis B, but the
      French Caribbean and Pacific territories are classified into areas of
      intermediate and high endemicity. In France vaccination programmes aimed at high
      risk groups were started in 1982 (including health care workers and patients
      receiving blood products) and the immunization of babies born of hepatitis B
      virus surface antigen (HBsAg)-positive mothers was reinforced in 1992.
      Considering the drawbacks and limited effect of targeted vaccination policies,
      universal vaccination targeted particularly to the preadolescent and adolescent
      population was initiated in 1994. In 1995, hepatitis B virus (HBV) vaccination
      was included in the infant immunization schedule. However, the emotion generated
      by the claim that HBV vaccination could have led to the development of central
      nervous system demyelinating disorders resulted in a marked decline of HBV
      vaccine use, both in the pediatric (23.3% vaccination coverage in children less
      than 13 years old) and in the adult population. The current coverage rates are
      likely to be insufficient to bring about a significant reduction in the control
      of hepatitis B in France. The success of universal immunization is highly
      dependent on reinstating the confidence of the public and health care
      professionals in the safety and efficacy of hepatitis B vaccines.

PMID- 16989268
TI  - Mass vaccination for annual and pandemic influenza.
AB  - Influenza virus causes annual epidemics and occasional pandemics. Frequent
      mutations in circulating influenza strains ("antigenic drift") result in the need
      for annual vaccination. More than two-thirds of persons in the U.S. are
      recommended for annual vaccination. Because influenza vaccine is available
      seasonally, mass vaccination strategies are well suited to its delivery. Although
      doctors offices are the most frequent setting for influenza vaccination overall,
      workplaces, clinics, and community sites (retail stores and pharmacies) also are
      common vaccination settings. Influenza vaccination also is delivered in mass
      vaccination clinics to health care workers and military personnel. Universal
      influenza vaccination, which has been recommended as a strategy to improve
      prevention by increasing vaccination coverage and providing indirect protection
      of adults by decreasing infection and transmission among children, would require
      expanded use of mass vaccination, for example in schools, as well as in the
      community. Influenza pandemics occur when a new influenza A subtype is introduced
      into the population ("antigenic shift"). Most or all of the population is
      susceptible to the pandemic virus and two doses of vaccine may be needed for
      protection. U.S. pandemic preparedness and response plans indicate that the
      entire population should be vaccinated beginning with defined priority groups
      including those who provide essential services including healthcare and those at
      highest risk of severe illness and death. Pandemic influenza vaccination will
      occur primarily through the public sector in mass clinic settings. Vaccination
      program planning must consider issues including coordination, staffing, clinic
      location and lay-out, security, record keeping, and communications. Exercising
      vaccination clinics is important for preparedness and can be done in the context
      of annual influenza vaccination.

PMID- 16989269
TI  - Is global measles eradication feasible?
AB  - Measles is one of most infectious diseases. Before the introduction of the
      measles vaccine, practically all children in the long run contracted measles. By
      the end of the 1980s most countries of the world had incorporated measles vaccine
      into their routine vaccination programs. Globally, some 800,000 deaths due to
      measles still occur every year, half of them in Africa. Eradication of measles
      would play an important role in improving child survival. The goal to eradicate
      measles from the Americas was set by the Pan American Sanitary Conference in
      1994. Progress to date has been remarkable. Measles is no longer an endemic
      disease in the Americas and interruption of transmission has been documented in
      most countries. As of August 2005, 3 years have elapsed since the detection of
      the last indigenous case in Venezuela in September 2002. This experience shows
      that interruption of measles transmission can be achieved and sustained over a
      long period of time and that global eradication is feasible if appropriate
      strategy is implemented. Even in a new paradigm in which eradication is not
      followed by the discontinuation of vaccination, eradication of measles will be a
      good investment to avoid expensive epidemics and save the almost one million
      children that die every year to infection with the measles virus. It is not a
      dream to think that we will se a world free of measles by the year 2015.

PMID- 16989270
TI  - Measles aerosol vaccination.
AB  - Measles ranks fifth among the five major childhood conditions which are
      responsible for 21% of all deaths in low and middle-income countries. Measles
      immunization is considered the most cost-effective public health intervention in
      the world. In recent years, there has been a critical need to identify
      alternative routes of measles immunization, which are rapid, reliable, cost
      effective, needle-free, and suitable for use in mass campaigns. Aerosol
      administration of measles vaccines in mass campaigns was first proposed by Dr.
      Albert Sabin. We review the different clinical trials that have been conducted
      using the classic Mexican device as well as issues regarding vaccine strain,
      presentation, and manufacturer. Results of clinical trials indicate that the
      method is safe and immunogenic in infants and school age children. The viral
      inoculum will probably need to be increased when administered to infants. From
      the logistical point of view, the use of the aerosol method has not been
      evaluated in routine immunization although feasibility of its routine
      implementation was proved in mass campaigns in Mexico. Cost savings will probably
      be demonstrated. As to licensure, its compliance with the appropriate
      international regulatory requirements for medical aerosol delivery devices is in
      process.

PMID- 16989271
TI  - Mass vaccination campaigns for polio eradication: an essential strategy for
      success.
AB  - Effective vaccines against poliomyelitis became available in the mid-1950s and
      early 1960s. Mass campaigns were an integral part of early control efforts.
      Thereafter, polio vaccines were used largely in routine childhood programs. The
      resolution in 1988 to eradicate polio globally led to the development of
      appropriate strategies to achieve this goal, including mass vaccination campaigns
      (i.e., national immunization days, sub-national immunization days and mop-up
      activities), to achieve the highest possible coverage in the shortest possible
      time. Unlike other vaccines, mass campaign use of oral poliovirus vaccine
      enhances the immunogenicity of this vaccine, primarily due to: (1) the decrease
      in the prevalence of other enteroviruses that potentially interfere with
      seroconversion; and (2) the secondary spread of vaccine virus from vaccinees to
      close contacts, resulting in seroconversion of some unvaccinated contacts. To
      reach the highest possible coverage, detailed planning, meticulous execution,
      careful supervision and standardized monitoring are critical. A number of
      innovative approaches to improve the quality and/or coverage have become the
      'standard' of supplemental immunization activities. These mass campaigns have led
      to dramatic decreases in the incidence of polio. This chapter reviews the
      scientific, operational and programmatic data on mass campaign use of polio
      vaccines, and summarize the lessons learnt from implementing the mass vaccination
      strategies used to eradicate poliomyelitis globally.

PMID- 16989272
TI  - Rubella mass campaigns.
AB  - The availability of vaccines that contain both measles and rubella components
      allows for the elimination of both diseases. Although routine infant vaccination
      with rubella vaccine has had profound effects on the incidence of both acquired
      and congenital rubella, mass vaccination rapidly stops circulation of the virus
      and prevents paradoxical increases in susceptibility of women that might result
      from decreased exposure in childhood. Whereas routine rubella vaccination has
      eliminated the infection from many developed countries, mass vaccination has
      rapidly accomplished the same goal in Latin America and the Caribbean, and is
      being applied in other developing country areas.

PMID- 16989273
TI  - Mass vaccination to control epidemic and endemic typhoid fever.

PMID- 16989274
TI  - Mass vaccination: solutions in the skin.
AB  - The skin is populated with Langerhans cells, thought to be efficient, potent
      antigen-presenting cells, that are capable of inducing protective immunity by
      targeting antigen delivery to the skin. Delivery to the skin may be accomplished
      by active delivery such as intradermal injection, use of patches or a combination
      of a universal adjuvant patch with injections. The robust immunity induced by
      skin targeting can lead to dose sparing, novel vaccines and immune enhancement in
      populations with poorly responsive immune systems, such as the elderly. Vaccine
      delivery with patches (transcutaneous immunization), may allow self
      administration, ambient temperature stabilization and ease of storage for
      stockpiling, leading to a new level of efficient vaccine distribution in times of
      crisis such as a bioterror event or pandemic influenza outbreak. The use of an
      adjuvant (immunostimulant) patch with injected vaccines has been shown in
      clinical studies to enhance the immune response to an injected vaccine. This can
      be used for dose sparing in pandemic influenza vaccines in critically short
      supply or immune enhancement for poor responders to flu vaccines such as the
      elderly. Transcutaneous immunization offers a unique safety profile, as adjuvants
      are sequestered in the skin and only delivered systemically by Langerhans cells.
      This results in an excellent safety profile and allows use of extremely potent
      adjuvants. The combination of the skin immune system, safe use of potent
      adjuvants and ease of delivery suggests that skin delivery of vaccines can
      address multiple unmet needs for mass vaccination scenarios.

PMID- 16989275
TI  - Hairy roots induced by Agrobacterium rhizogenes and production of regenerative
      plants in hairy root cultures in maize.
AB  - Hairy roots of maize were induced by infecting 15-d calli with Agrobacterium
      rhizogenes. The hairy roots cultured in hormone-free media showed the vigorous
      growth and typical hairy root features. The regenerated plants were produced from
      hairy roots in MS media supplemented with 1.6 mg/L ZT and 0.4 mg/L NAA. The PCR
      Southern hybridization demonstrated that T-DNA had been integrated into the
      chromosome of regenerated plants.

PMID- 16989276
TI  - The role of chloroplast NAD(P)H dehydrogenase in protection of tobacco plant
      against heat stress.
AB  - After incubation at 42 degrees C for more than 48 h, brown damages occurred on
      the stems of tobacco (Nicotiana tabacum L.) ndhC-ndhK-ndhJ deletion mutant
      (deltandhCKJ), followed by wilt of the leaves, while less the phenotype was found
      in its wild type (WT). Analysis of the kinetics of post-illumination rise in
      chlorophyll fluorescence indicated that the PSI cyclic electron flow and the
      chlororespiration mediated by NAD(P)H dehydrogenase (NDH) was significantly
      enhanced in WT under the high temperature. After leaf disks were treated with
      methyl viologen (MV), photosynthetic apparatus of deltandhCKJ exhibited more
      severe photo-oxidative damage, even bleaching of chlorophyll. Analysis of P700
      oxidation and reduction showed that the NDH mediated cyclic electron flow
      probably functioned as an electron competitor with Mehler reaction, to reduce the
      accumulation of reactive oxygen species (ROS). When leaf disks were heat stressed
      at 42 degrees C for 6 h, the photochemical activity declined more markedly in
      deltandhCKJ than in WT, accompanied with more evident decrease in the amount of
      soluble Rubisco activase. In addition, the slow phase of millisecond-delayed
      light emission (ms-DLE) of chlorophyll fluorescence indicated that NDH was
      involved in the building-up of transthylakoid proton gradient (deltapH), while
      the consumption of deltapH was highly inhibited in deltandhCKJ after heat stress.
      Based on the results, we supposed that the cyclic electron flow mediated by NDH
      could be stimulated under the heat stressed conditions, to divert excess
      electrons via chlororespiration pathway, and sustain CO2 assimilation by
      providing extra deltapH, thus reducing the photooxidative damage.

PMID- 16989277
TI  - Analysis and validation of genome-specific DNA variations in 5' flanking
      conserved sequences of wheat low-molecular-weight glutenin subunit gene.
AB  - The thirty-three 5' flanking conserved sequences of the known low-molecular
      weight subunit (LMW-GS) genes have been divided into eight clusters, which was in
      agreement with the classification based on the deduced N-terminal protein
      sequences. The DNA polymorphism between the eight clusters was obtained by
      sequence alignment, and a total of 34 polymorphic positions were observed in the
      approximately 200 bp regions, among which 18 polymorphic positions were candidate
      SNPs. Seven cluster-specific primer sets were designed for seven out of eight
      clusters containing cluster-specific bases, with which the genomic DNA of the
      ditelosomic lines of group 1 chromosomes of a wheat variety 'Chinese Spring' was
      employed to carry out chromosome assignment. The subsequent cloning and DNA
      sequencing of PCR fragments validated the sequences specificity of the 5'
      flanking conserved sequences between LMW-GS gene groups in different genomes.
      These results suggested that the coding and 5' flanking regions of LMW-GS genes
      are likely to have evolved in concerted fashion. The seven primer sets developed
      in this study could be used to isolate the complete ORFs of seven groups of LMW
      GS genes, respectively, and therefore possess great value for further research in
      the contributions of a single LMW-GS gene to wheat quality in the complex genetic
      background and the efficient selections of quality-related components in breeding
      programs.

PMID- 16989278
TI  - Evaluation of genetic diversity in Chinese indigenous chicken breeds using
      microsatellite markers.
AB  - China is rich in chicken genetic resources, and many indigenous breeds can be
      found throughout the country. Due to poor productive ability, some of them are
      threatened by the commercial varieties from domestic and foreign breeding
      companies. In a large-scale investigation into the current status of Chinese
      poultry genetic resources, 78 indigenous chicken breeds were surveyed and their
      blood samples collected. The genomes of these chickens were screened using
      microsatellite analysis. A total of 2740 individuals were genotyped for 27
      microsatellite markers on 13 chromosomes. The number of alleles of the 27 markers
      ranged from 6 to 51 per locus with a mean of 18.74. Heterozygosity (H) values of
      the 78 chicken breeds were all more than 0.5. The average H value (0.622) and
      polymorphism information content (PIC, 0.573) of these breeds suggested that the
      Chinese indigenous chickens possessed more genetic diversity than that reported
      in many other countries. The fixation coefficients of subpopulations within the
      total population (F(ST)) for the 27 loci varied from 0.065 (LEI0166) to 0.209
      (MCW0078), with a mean of 0.106. For all detected microsatellite loci, only one
      (LEI0194) deviated from Hardy-Weinberg equilibrium (HWE) across all the
      populations. As genetic drift or non-random mating can occur in small
      populations, breeds kept on conservation farms such a Langshan chicken generally
      had lower H values, while those kept on large populations within conservation
      regions possessed higher polymorphisms. The high genetic diversity in Chinese
      indigenous breeds is in agreement with great phenotypic variation of these
      breeds. Using Nei's genetic distance and the Neighbor-Joining method, the
      indigenous Chinese chickens were classified into six categories that were
      generally consistent with their geographic distributions. The molecular
      information of genetic diversity will play an important role in conservation,
      supervision, and utilization of the chicken resources.

PMID- 16989279
TI  - Cloning and analysis of differentially expressed ESTs in swine muscle tissue.
AB  - The obvious difference in muscle growth and meat quality traits exists between
      Chinese indigenous pig and exotic pigs. In order to study the reason of these
      phenotypic differences and search the potential gene related to growth and meat
      quality traits, silver-stained mRNA differential display technique was used to
      detect the difference with mRNA of loin-eye muscle tissue from maturity pigs of
      Lantang in Guangdong Province and Large Yorkshire. One of the newly discovered
      expressed sequence tag (ESTsp3) was analyzed by using bioinformatic technique.
      The results showed: (1) nearly 2000 cDNA fragments were detected with 30 primer
      pairs, and 6 differentially expressed ESTs in the loin-eye muscle tissues from
      the two breeds were isolated and obtained. The differential fragments were cloned
      and sequenced. The all sequences were recorded in the GenBank. (2) The 786 bp
      fragment of ESTsp3 was obtained with in silico elongation system, the ORF
      analysis revealed that it existed as an 83 aa complete open reading frame, and
      the elongation sequences were verified by RT-PCR. The analysis of in silico
      expression profile showed that ESTsp3 is expressed in various growth stages and
      in most tissues and organs, such as soft tissue, skin, skeletal muscle and
      kidney, but with variant expression quantity.

PMID- 16989280
TI  - Effects of mating status on copulation investment by male bushcricket Gampsocleis
      gratiosa (Tettigoniidae, Orthoptera).
AB  - Male's copulation investment, including spermatophore and sperm investment were
      very high in the Chinese bushcricket Gampsocleis gratiosa. The effects of mating
      status of both males and females on male's copulation investment were examined in
      this study. The fresh weight of spermatophylax increased positively with the
      weight of males' body. This indicated that the nutritional investment during
      copulation depended on male's quality. Spermatophore investment showed
      insignificant differences in every copulation protocols. This finding supported
      the paternal investment hypothesis, that is, males contributed to their offspring
      with little attention to their partners. Sperm releasing per ejaculation varied
      significantly among the trials. Males decreased 54.19% sperm in second mating
      than in its first mating, demonsrated that males regarded the first mating
      highly, and were more prudent in subsequent mating. These males' strategies may
      contribute to the viability of the offspring.

PMID- 16989281
TI  - Nested multiplex PCR--a feasible technique to study partial community of
      arbuscular mycorrhizal fungi in field-growing plant root.
AB  - Plant can be infected by different arbuscular mycorrhizal fungi, but little is
      known about the interaction between them within root tissues mainly because
      different species cannot be distinguished on the basis of fungal structure.
      Accurate species identification of Arbuscular mycorrhizal fungi (AMF) colonized
      in plant roots is the cornerstone of mycorrhizal study, yet this fundamental step
      is impossible through its morphological character alone. For accurate, rapid and
      inexpensive detection of partial mycorrhizal fungal community in plant roots, a
      nested multiplex polymerase chain reaction (PCR) was developed in this study.
      Five discriminating primers designed based on the variable region of the 5' end
      of the large ribosomal subunit were used in the experiment for testing their
      specificity and the sensitivity in nested PCR by using spores from Glomus mosseae
      (BEG12), Glomus intraradices (BEG141), Scutellospora castaneae (BEG1) and two
      unidentified Glomus sp. HAUO3 and HAUO4. The feasibility assay of nested
      multiplex PCR was conducted by use of spore mixture, Astragalus sinicum roots co
      inoculated with 4 species of arbuscular mycorrhizal fungi from pot cultures and
      15 different field-growing plant roots respectively after analyses of the
      compatibility of primers. The result indicated that the sensitivity was in the
      same range as that of the corresponding single PCR reaction. Overall accuracy was
      95%. The efficiency and sensitivity of this multiplex PCR procedure provided a
      rapid and easy way to simultaneously detect several of arbuscular mycorrhiza
      fungal species in a same plant root system.

PMID- 16989282
TI  - Glycine origin of the methyl substituent on C7'-N of octodiose for the
      biosynthesis of apramycin.
AB  - Apramycin is unique in the aminoglycoside family due to its octodiose moiety.
      However, either the biosynthesis process or the precursors involved are largely
      unknown. Addition of glycine, as well as serine or threonine, to the Streptomyces
      tenebrabrius UD2 fermentation medium substantially increases the production of
      apramycin with little effect on the growth of mycelia, indicating that glycine
      and/or serine might be involved in the biosynthesis of apramycin. The 13C-NMR
      analysis of [2-13C] glycine-fed (25% enrichment) apramycin showed that glycine
      specifically and efficiently incorporated into the only N-CH3 substituent of
      apramycin on the C7' of the octodiose moiety. We noticed that the in vivo
      concentration of S-adenosyl methionine increased in parallel with the addition of
      glycine, while the addition of methione in the fermentation medium significantly
      decreased the productivity of apramycin. Therefore, the methyl donor function of
      glycine is proposed to be involved in the methionine cycle but methionine itself
      was proposed to inhibit the methylation and methyl transfer processes a
      previously reported for the case of rapamycin. The 15N NMR spectra of [2
      13C,15N]serine labeled apramycin indicated that serine may also act as a limiting
      precursor contributing to the -NH2 substituents of apramycin.

PMID- 16989283
TI  - The effect of decreasing alkalinity on microbial community dynamics in a sulfate
      reducing bioreactor as analyzed by PCR-SSCP.
AB  - PCR-single-strand conformation polymorphism (SSCP) and Southern blotting
      techniques were adopted to investigate microbial community dynamics in a sulfate
      reducing bioreactor caused by decreasing influent alkalinity. Experimental
      results indicated that the sulfate-removal rate approached 87% in 25 d under the
      conditions of influent alkalinity of 4000 mg/L (as CaCO3) and sulfate-loading
      rate of 4.8 g/(L*d), which indicated that the bioreactor started up successfully.
      The analysis of microbial community structure in this stage showed that
      Lactococcus sp., Anaerofilum sp. and Kluyvera sp. were dominant populations. It
      was found that when influent alkalinity reduced to 1000 mg/L, sulfate-removal
      rate decreased rapidly to 35% in 3 d. Then influent alkalinity was increased to
      3000 mg/L, the sulfate-removal rate rose to 55%. Under these conditions, the
      populations of Dysgonomonas sp., Sporobacte sp., Obesumbacterium sp. and
      Clostridium sp. got to rich, which predominated in the community together with
      Lactococcus sp., Anaerofilum sp. and Kluyvera sp. However, when the alkalinity
      was decreased to 1500 mg/L, the sulfate-removal rate rose to and kept stable at
      70% and populations of Dysgonomonas sp., Sporobacter sp. and Obesumbacterium sp.
      died out, while some strains of Desulfovibrio sp. and Clostridium sp. increased
      in concentration. In order to determine the minimum alkalinity value that the
      system could tolerate, the influent alkalinity was decreased from 1500 to 400
      mg/L secondly. This resulted in the sulfate-removal rate, pH value and effluent
      alkalinity dropping quickly. The amount of Petrotoga sp., Prevotella sp.,
      Kluyvera sp. and Neisseria sp. reduced obviously. The result data from Southern
      blotting indicated that the amount of sulfate-reducing bacteria (SRBs) decreased
      with influent alkalinity dropping. Analysis of the microbial community structure
      and diversity showed that the SRBs populations were very abundant in the
      inoculated activated sludge and the alkalinity decrease caused the reduction of
      the populations noted. Most of resident populations in the bioreactor were
      fermentative acidogenic bacteria (FABs), among which the phylum Firmicute was in
      the majority, but SRBs were very few. This community structure demonstrates the
      cooperation between SRBs and FABs, which sustains the system's high sulfate
      removal and operation stability.

PMID- 16989284
TI  - Nitric oxide mediates the fungal elicitor-induced puerarin biosynthesis in
      Pueraria thomsonii Benth. suspension cells through a salicylic acid (SA)
      dependent and a jasmonic acid (JA)-dependent signal pathway.
AB  - Nitric oxide (NO) has emerged as a key signaling molecule in plant secondary
      metabolite biosynthesis recently. In order to investigate the molecular basis of
      NO signaling in elicitor-induced secondary metabolite biosynthesis of plant
      cells, we determined the contents of NO, salicylic acid (SA), jasmonic acid (JA),
      and puerarin in Pueraria thomsonii Benth. suspension cells treated with the
      elicitors prepared from cell walls of Penicillium citrinum. The results showed
      that the fungal elicitor induced NO burst, SA accumulation and puerarin
      production of P. thomsonii Benth. cells. The elicitor-induced SA accumulation and
      puerarin production was suppressed by nitric oxide specific scavenger cPITO,
      indicating that NO was essential for elicitor-induced SA and puerarin
      biosynthesis in P. thomsonii Benth. cells. In transgenic NahG P. thomsonii Benth.
      cells, the fungal elicitor also induced puerarin biosynthesis, NO burst, and JA
      accumulation, though the SA biosynthesis was impaired. The elicitor-induced JA
      accumulation in transgenic cells was blocked by cPITO, which suggested that JA
      acted downstream of NO and its biosynthesis was controlled by NO. External
      application of NO via its donor sodium nitroprusside (SNP) enhanced puerarin
      biosynthesis in transgenic NahG P. thomsonii Benth. cells, and the NO-triggered
      puerarin biosynthesis was suppressed by JA inhibitors IBU and NDGA, which
      indicated that NO induced puerarin production through a JA-dependent signal
      pathway in the transgenic cells. Exogenous application of SA suppressed the
      elicitor-induced JA biosynthesis and reversed the inhibition of IBU and NDGA on
      elicitor-induced puerarin accumulation in transgenic cells, which indicated that
      SA inhibited JA biosynthesis in the cells and that SA might be used as a
      substitute for JA to mediate the elicitor- and NO-induced puerarin biosynthesis.
      It was, therefore, concluded that NO might mediate the elicitor-induced puerarin
      biosynthesis through SA- and JA-dependent signal pathways in wildtype P.
      thomsonii Benth. cells and transgenic NahG cells respectively.

PMID- 16989285
TI  - Long-term engraftment of p18(INK4C)-deficient hematopoietic stem cells is
      enhanced in the sublethally-irradiated recipients.
AB  - Non-myeloablative regimens for host conditioning have been widely used in
      clinical hematopoietic stem cell transplantation due to their reduced toxicity on
      the recipients. But a milder conditioning regimen may require a higher engrafting
      ability of donor stem cells in competing with endogenous stem cells. Thus, new
      strategies for enhancing the competitiveness of donor stem cells in non
      myeloablative recipients would have important implications for current clinical
      stem cell transplantation. It is known that the absence of p18(INK4C) (p18) gene
      can enhance the self-renewal potential of hematopoietic stem cells (HSCs). We
      applied the approach of competitive bone marrow transplantation to evaluate the
      impact of p18 gene deletion on long-term engraftment of HSCs in sublethally
      irradiated hosts. We found that p18(-/-) HSCs had a significant advantage over
      wild-type HSCs during long-term engraftment in the mouse recipients that received
      a sub-lethal irradiation (5-Gy). The engraftment efficiency of p18(-/-) HSCs in
      the sub-lethally irradiated recipients was similar to that in the lethally
      irradiated (10-Gy) recipients. Our current study demonstrates that enhanced
      engraftment of donor HSCs in the absence of p18 does not strictly depend on the
      dose of irradiation used for host conditioning. Therefore, p18 might serve as a
      potential drug target for increasing the efficacy of stem cell transplant in the
      patients that are preconditioned with either a myeloablative or non-myeloablative
      regimen.

PMID- 16989286
TI  - The study of neighboring nucleotide composition and transition/transversion bias.
AB  - Base substitution is one of the raw fuels that produce genetic variation and
      drive evolution. Recent studies have shown that the genome components affect
      mutation patterns to some extent. In order to infer the correlation between the
      Transition/Transversion ratio (Ts/Tv) and the number of immediately adjacent A
      and T nucleotides, we investigated 3611007 Oryza sativa SNPs (including 45462
      coding SNPs, and 242811 intronic SNPs) and 32019 Arabidopsis SNPs. The results
      show that Ts/Tv is negatively correlated with the number of immediately adjacent
      A and T in O. sativa and Arabidopsis. We further calculated AT2 (the number of
      SNPs whose immediately adjacent nucleotides are either A or T) and AT0 (the
      number of SNPs whose immediately adjacent nucleotides are either C or G) for all
      6 types of SNPs. C/G SNP of O. sativa and Arabidopsis has the highest AT2/AT0,
      which denotes C/G SNP may be influenced by the adjacent A and T nucleotides
      mostly. For SNPs in O. sativa, the neighboring effect of A and T nucleotides is
      limited to 2 nucleotides on both sides; for SNPs in Arabidopsis, the effect
      extends no more than 4 nucleotides on both sides.

PMID- 16989287
TI  - Regulatory mechanisms for abnormal expression of the human breast cancer specific
      gene 1 in breast cancer cells.
AB  - Breast cancer-specific gene 1 (BCSG1), also referred as synuclein y, was
      originally isolated from a human breast cancer cDNA library and the protein is
      mainly localized to presynaptic terminals in the nervous system. BCSG1 is not
      expressed in normal or benign breast lesions, but expressed at an extremely high
      level in the vast majority of the advanced staged breast carcinomas and ovarian
      carcinomas. Overexpression of BCSG1 in cancer cells led to significant increase
      in cell proliferation, motility and invasiveness, and metastasis. To elucidate
      the molecular mechanism and regulation for abnormal transcription of BCSG1, a
      variety of BCSG1 promoter luciferase reporters were constructed including 3' end
      deleted sequences, Sp1 deleted, and activator protein-1 (AP1) domains mutated.
      Transient transfection assay was used to detect the transcriptional activation of
      BCSG1 promoters. Results showed that the Sp1 sequence in 5'-flanking region was
      involved in the basal transcriptional activities of BCSG1 without cell-type
      specificity. In comparison to pGL3-1249, the reporter activities of pGL3-1553 in
      BCSG1-negative MCF-7 cells and pGL3-1759 in HepG2 cells were notably decreased.
      Mutations at AP1 sites in BCSG1 intron 1 significantly reduced the promoter
      activity in all cell lines. Transcription factors, c-jun, c-fos and cyclin AMP
      responsive element binding (CREB) protein, could markedly enhance the promoter
      activities. Thus, our results suggest that the abnormal expression of BCSG1 in
      breast cancer cells is likely regulated by multiple mechanisms. The 5' flanking
      region of BCSG1 provides the basal transcriptional activity without cell type
      specificity. A critical promoter element involved in abnormal expression of BCSG1
      presents in the first exon. The cell type specificity of BCSG1 transcription is
      probably affected through intronic cis-regulatory sequences. AP1 domains in the
      first intron play an important role in control of BCSG1 transcription.

PMID- 16989288
TI  - Abstinence, anticipation, reduction, and treatment (AART): a stepwise approach to
      the management of atypical antipsychotic side effects.
AB  - Antipsychotic medications, specifically the atypical agents, serve as first-line
      treatment options for patients with psychotic disorders, including individuals
      with schizophrenia or schizoaffective disorder. Atypical antipsychotics are also
      often prescribed off-label as either the primary treatment or as an adjunctive
      treatment for individuals with other disorders, including mood disorders without
      psychosis, behavioral disorders, and insomnia. Despite the generally superior
      side-effect profiles of atypical antipsychotics compared with typical
      antipsychotic agents, the atypicals have been associated with a number of serious
      side effects, including metabolic disorders, cardiovascular disorders, seizures,
      hyperprolactinemia, and movement disorders. This article offers a stepwise
      approach to the management of antipsychotic side effects: Abstinence,
      Anticipation, Reduction, and Treatment (AART). The steps in AART are
      hierarchical, but often overlap in the areas of risk prevention and minimization.
      The authors discuss issues relevant to each level of intervention and provide
      suggestions for integrating the AART approach into a comprehensive treatment
      plan. By incorporating this stepwise approach into their clinical decision-making
      process, prescribers may be able to optimize the risk:benefit ratio associated
      with the prescription of atypical antipsychotics.

PMID- 16989289
TI  - Single enantiomer drugs: should they be developed?
AB  - Biological interactions are stereoselective; thus the interactions of drugs with
      corresponding biological targets must also be stereoselective. However, many
      drugs used today are racemic mixtures. For example, approximately 25% or 1 in 4
      marketed drugs are mixtures of agents (racemates) rather than single chemical
      entities (enantiomers). One of these enantiomers can be inactive or even
      counterproductive to the therapeutic use of the drug: either by reducing the
      efficacy of the active enantiomer or by causing unnecessary tolerability problems
      or even toxicity through differential pharmacodynamics. The presence of a
      therapeutically inactive or counterproductive enantiomer can also complicate the
      pharmacokinetics of the active enantiomer and the interpretation of the
      therapeutic drug monitoring (e.g., plasma levels) if the assay is not capable of
      separately quantitating the two enantiomers. This article reviews the history of
      stereoisomers and the relevant pharmacological principles, then discusses recent
      changes in rules governing drug approval and the potential advantages to the
      patient and the manufacturer of developing single enantiomers.

PMID- 16989290
TI  - Anxious-depressive comorbidity: effects on HPA axis and CNS noradrenergic
      functions.
AB  - Psychiatric comorbidity is all too common. An important example is the high
      comorbidity frequency of depressive and anxiety disorders, 25%-50%, much higher
      than the 5% or less expected by chance. Possible reasons for this comorbidity
      include definitional, environmental, and biological factors. Few previous studies
      have assessed, with proper methodology, potential biological changes associated
      with this co-occurrence. We assessed both hypothalamic-pituitary-adrenocortical
      axis (HPA) responses to the Trier Social Stress Test and growth hormone (GH)
      responses to clonidine, a centrally active alpha-2 adrenoreceptor agonist, in 15
      persons with major depression without anxiety, 15 with an anxiety disorder
      without depression, 18 comorbid for anxiety and depression, and 48 individually
      matched control subjects. Individuals with depression only were normal on both
      tests, while those with anxiety only had normal HPA responses but blunted GH
      responses. Comorbid individuals showed elevated HPA responses and only those
      comorbid persons with anxiety symptoms predominant also showed blunted GH
      responses. Controls and anxiety-only subjects showed significant correlations
      between the results of the two tests. This association was disrupted by the
      presence of depression with or without comorbidity. Comorbidity is fundamental to
      understanding the pathophysiologies of depression and anxiety.

PMID- 16989291
TI  - Serotonin and norepinephrine transporter binding profile of SSRIs.
AB  - Even today, pharmacotherapy for mood disorders is based almost entirely on the
      observation in the 1950s and 1960s that agents that enhance monoamine transmitter
      activity are effective antidepressants. Preclinical studies have shown that long
      term administration of nearly all effective antidepressants increases the
      efficiency of postsynaptic serotonin transmission; many also modify central
      noradrenergic activity. For the majority of antidepressants, these changes are
      the result of their ability to block serotonin and/or norepinephrine activity at
      their "presynaptic uptake sites" (i.e., at the serotonin transporter [SERT] or
      the norepinephrine transporter [NET]). Drugs that are highly selective for one
      transporter over another have been demonstrated to be effective and tolerable,
      whereas agents that act on multiple transporters may not necessarily achieve
      better efficacy and may result in additional adverse events. The rationale for
      the use of drugs that affect multiple transports is based on the suggestion that
      antidepressants that block both the SERT and the NET may provide better efficacy.
      This can only be determined through empirical studies.

PMID- 16989292
TI  - Cytokines and late-life depression.
AB  - Cytokines are peripherally and centrally produced proteins that regulate immune
      and immunological responses. They also have neurochemical, neuroendocrine and
      behavioural effects similar to those seen in patients with depression. A review
      of the literature reveals several cytokines, including IL-1beta, IL-2, IL-6 and
      IFN, have been shown to be elevated in plasma of working-age adults with
      depression and dysthymia. A more detailed review of the literature also reveals
      similar associations between cytokines and late-life depression, with IL-1beta,
      IL-6 and TNF-alpha all being reported to be elevated in both depression and
      dysthymia. It has been hypothesized that cytokines provide the link between
      depression, neurochemical changes and the altered HPA axis that are known to
      occur in this disease, and evidence is presented that supports this view.
      However, the evidence that antidepressants may have effects on cytokines is
      conflicting. Increased cytokine levels may also serve as an explanation for the
      increased risk for vascular disease that has been associated with depression, and
      a possible mechanism for this is discussed.

PMID- 16989293
TI  - The CATIE study and its implications for antipsychotic drug use.

PMID- 16989294
TI  - Attack back!

PMID- 16989295
TI  - Caregiving in rural African American families for older adult stroke survivors.
AB  - Stroke disproportionately affects African Americans, but stroke caregiving
      research on this group is missing from the literature. The purpose of this
      grounded theory study was to examine rural African American family caregiving for
      older adult stroke survivors. Eight African American families participated in the
      study. The sample included 8 stroke survivors, 8 primary caregivers, and 18
      secondary caregivers. Data were generated through interactive interviews and
      focused observations that took place in caregivers' or stroke survivors' homes. A
      multistep data analysis technique incorporating the constant comparative method
      was used to uncover the basic social psychological problem of transitions and a
      four-stage basic social process of striking a balance. The families coped with
      the transitions of stroke caregiving by using strategies termed here deciding to
      care, dividing care, protective care, and coming to terms. The substantive theory
      of caregiving provides nurses with a framework to help rural African American
      families care for their older relatives who have experienced stroke.

PMID- 16989296
TI  - Management of lipid disorders for stroke prevention.
AB  - Lipid disorders are common among stroke patients, many of whom also have coronary
      artery disease. Cholesterol, a lipid, plays a major role in the development of
      plaque and resulting atherosclerosis. Understanding laboratory values, stroke
      risk, pharmacological management, and lifestyle modifications associated with
      lipid disorders is critical to improving care for stroke patients with lipid
      disorders.

PMID- 16989297
TI  - Causal attributions and health behavior choices among stroke and transient
      ischemic attack survivors.
AB  - To reduce the risk of a recurring event in patients who have suffered an initial
      stroke or transient ischemic attack (TIA), nurses are challenged with
      implementing and promoting changes in lifestyle and adherence to treatment
      regimens. Assessing patients' beliefs about the cause of the stroke or TIA is
      important to understanding their subsequent health behaviors. This study
      describes the causal attributions and health behavior choices of 9 participants
      following a stroke or TIA. Attributions were categorized as internal or external
      and cross-tabulated by controllability. The attributions were compared with
      health behavior choices. All participants attempted to make causal attributions,
      both internal (e.g., anxiety, hypertension, lifestyle) and external (e.g.,
      stress, fate). Those making external attributions demonstrated poorer health
      behavior choices than those making internal attributions; controllability had no
      influence on behavior. Patients diagnosed more than 6 months before the study
      tended to make more external attributions. The results can help nurses understand
      the beliefs that drive the health behavior choices made by stroke and TIA
      survivors and guide them in tailoring prevention strategies and engaging patients
      in preventive activities.

PMID- 16989298
TI  - Nursing priorities in caring for patients with intracerebral hemorrhage.
AB  - Patients afflicted with intracerebral hemorrhage (ICH) experience potentially
      devastating neurological sequelae; current therapy for ICH remains supportive.
      However, hemostatic therapy with recombinant activated factor VIIa holds promise
      for decreasing the morbidity and mortality of patients following an ICH. Nurses
      who are the responsible clinicians at the bedside often find it challenging to
      care for these patients. This article discusses the priorities that nurses need
      to determine as they balance the overall needs of the patient, incorporating
      recombinant activated factor VIIa as a new treatment for ICH.

PMID- 16989299
TI  - Integrating self-efficacy and aging theories to promote behavior change and
      reduce stroke risk.
AB  - The increasing incidence of stroke has resulted in the establishment of secondary
      stroke prevention clinics. Such clinics have successfully reduced wait-to
      treatment times for individuals diagnosed with transient ischemic attack or minor
      stroke. In addition to improving access to consultation, diagnosis, and
      treatment, healthcare clinics need to implement behavioral risk-reduction
      programs tailored to older adults to help them better adhere to treatment
      regimens. The integration of two social-psychological theories--(a) self-efficacy
      and (b) selection, optimization, and compensation-provide the foundation for an
      approach that could lead to the development of evidence-based behavioral risk
      reduction programs for older adults at high risk of stroke.

PMID- 16989300
TI  - Successful implementation of the National Institutes of Health Stroke Scale on a
      stroke/neurovascular unit.
AB  - The National Institutes of Health Stroke Scale (NIHSS) is accepted as the
      definitive clinical examination to assess stroke severity. This project examined
      barriers to implementation and NIHSS use by registered nurses on a
      stroke/neurovascular Unit. Staff members were surveyed to determine nurse
      perceived barriers to the routine use of the NIHSS. Survey results were used to
      create interventions including staff education, emphasis on NIHSS assessment
      during interdisciplinary rounds, and use of pocket cards. When the survey was
      redistributed 9 months later to verify results of the quality improvement
      initiative and guide further interventions, NIHSS assessment had increased from
      12% to 69%. NIHSS scores have been linked to an existing outcomes database to
      monitor acute stroke treatment and inpatient management outcomes.

PMID- 16989301
TI  - Poststroke depression incidence and risk factors: an integrative literature
      review.
AB  - Depression is a frequent complication of stroke, but few nurse researchers have
      studied poststroke depression (PSD). We reviewed all published research (January
      1980-March 2005) that examined the incidence of and risk factors for depression
      among stroke survivors during the first 3 months after stroke. Many of the 49
      studies reviewed were complicated by methodological limitations, including
      differing definitions of stroke and depression, the use of screening instruments
      to diagnose depression, selection bias, assessment at different time intervals
      poststroke, exclusion of patients with physical or cognitive impairments, and
      failure to control for associated variables. The incidence of PSD ranged from 5%
      to 63%. A history of depression, increased stroke severity, and poststroke
      cognitive or physical impairment were found to be risk factors for PSD.

PMID- 16989302
TI  - Advancing nursing practice: the role of the nurse practitioner in an acute stroke
      program.
AB  - Both patient and staff satisfaction with the SNP role has been high as it relates
      to quality of care delivery and accessibility of care and service. In particular,
      patients express satisfaction with the continuity of care experienced throughout
      the stroke care continuum, from acute in-hospital care to postdischarge follow
      up. Improvements have been realized in systems and processes of care with the
      implementation of the SNP role. These include reductions in door-to-needle times
      in the administration of tPA (from 90 minutes to 60 minutes), rapid assessment
      and diagnostic interventions through coordination of are activities (e.g., door
      to-CT scan times reduced from 60 minutes to 30 minutes), and faster consultation
      responses within the organization. Instituting the nurse practitioner role early
      in the development of the Calgary Stroke Program enhanced patient care while
      advancing the nursing discipline. The SNP has created a role that extends beyond
      that of physician helper to an autonomous nursing practice that has been
      beneficial to both patients with stroke and the regional healthcare delivery
      system. With the ability to practice autonomously, the nurse practitioner can aid
      in the expedient delivery of complex, comprehensive stroke care, as has been the
      case in the Calgary Stroke Program.

PMID- 16989303
TI  - Chemical composition and phytotoxicity of volatile essential oil from intact and
      fallen leaves of Eucalyptus citriodora.
AB  - A total of 23 volatile constituents was identified and characterized by GC and GC
      MS in the volatile essential oil extracted from intact (juvenile and adult) and
      fallen (senescent and leaf litter) leaves of lemon-scented eucalyptus (Eucalyptus
      citriodora Hook.). The leaves differed in their pigment, water and protein
      content, and C/N ratio. The oils were, in general, monoterpenoid in nature with
      18 monoterpenes and 5 sesquiterpenes. However, a great variability in the amount
      of essential oils and their individual constituents was observed in different
      leaf tissues. The amount was maximum in the senescent leaves collected from the
      floor of the tree closely followed by that from juvenile leaves. In all, 19
      constituents were identified in oil from juvenile and senescent leaves compared
      to 23 in adult leaves and 20 in leaf litter, respectively. Citronellal, a
      characteristic monoterpene of the oil reported hitherto was found to be more (77
      78%) in the juvenile and senescent leaves compared to 48 and 54%, respectively,
      in the adult leaves and leaf litter. In the adult leaves, however, the content of
      citronellol--another important monoterpene-- was very high (21.9%) compared to
      other leaf types (7.8-12.2%). Essential oil and its two major monoterpenes viz.
      citronellal and citronellol were tested for their phytotoxicity against two weeds
      (Amaranthus viridis and Echinochloa crus-galli) and two crops (Triticum aestivum
      and Oryza sativa) under laboratory conditions. A difference in the phytotoxicity,
      measured in terms of seedling length and dry weight, of oil from different leaves
      and major monoterpenes was observed. Oil from adult leaves was found to be most
      phytotoxic although it occurs in smaller amount (on unit weight basis). The
      different toxicity of different oil types was due to the relative amount of
      individual monoterpenes present in the oil, their solubility and interactive
      action. The study concludes that oil from senescent and juvenile leaves being
      rich in citronellal could be used as commercial source of citronellal whereas
      that from adult leaves for weed management programmes as it was the most
      phytotoxic.

PMID- 16989304
TI  - (-)-Agelasidine A from Agelas clathrodes.
AB  - (-)-Agelasidine A was identified from the methanol extract of the marine sponge
      Agelas clathrodes for the first time together with zooanemonin, 1
      carboxymethylnicotinic acid, hymenidin, mukanadins A and C, monobromodispacamide,
      agelasidine D, 2-amide-4-bromopyrrole, O-methyltryptophan and an agelasines
      mixture. The structures were characterized by spectroscopic methods. (-)
      Agelasidine A was tested for antibacterial and antifungal activities and shown to
      act as a bacteriostatic agent as it inhibited the growth of Staphylococcus aureus
      and partially the growth of other bacteria.

PMID- 16989305
TI  - In vivo analgesic and anti-inflammatory activities of ursolic acid and oleanoic
      acid from Miconia albicans (Melastomataceae).
AB  - The aim of this work was to use in vivo models to evaluate the analgesic and anti
      inflammatory activities of ursolic acid (UA) and oleanoic acid (OA), the major
      compounds isolated as an isomeric mixture from the crude methylene chloride
      extract of Miconia albicans aerial parts in an attempt to clarify if these
      compounds are responsible for the analgesic properties displayed by this plant.
      Ursolic acid inhibited abdominal constriction in a dose-dependent manner, and the
      result obtained at a content of 40 mg kg(-1) was similar to that produced by
      administration of acetylsalicylic acid at a content of 100 mg kg(-1). Both acids
      reduced the number of paw licks in the second phase of the formalin test, and
      both of them displayed a significant anti-inflammatory effect at a content of 40
      mg kg(-1). It is noteworthy that the administration of the isolated mixture,
      containing 65% ursolic acid/35% oleanolic acid, did not display significant
      analgesic and anti-inflammatory activities. On the basis of the obtained results,
      considering that the mixture of UA and OA was poorly active, it is suggested that
      other compounds, rather than UA and OA, should be responsible for the evaluated
      activities in the crude extract, since the crude extract samples displayed good
      activities.

PMID- 16989306
TI  - Cytotoxic and proapoptotic activity of diterpenoids from in vitro cultivated
      Salvia sclarea roots. Studies on the leukemia cell lines.
AB  - Four diterpenoids, ferruginol, salvipisone, aethiopinone and 1-oxoaethiopinone,
      were isolated from transformed roots of Salvia sclarea. Salvipisone and
      aethiopinone showed relatively high cytotoxicity against HL-60 and NALM-6
      leukemia cells (IC50 range 0.6-7.7 microg/ mL which is equal to 2.0-24.7 microM),
      whereas 1-oxoaethiopinone and ferruginol were less active in this regard.
      Moreover, we have found that all four diterpenoids of S. sclarea had equal
      cytotoxic activity against parental HL-60 and multidrug-resistant HL-60 ADR
      cells, what indicates that they are poor substrates for transport by multidrug
      resistance-associated protein (MRP1). Caspase-3 activity determinations showed
      that salvipisone and aethiopinone were able to induce apoptosis in a time- and
      concentration-dependent manner. The results obtained in this study show that S.
      sclarea diterpenoids aethiopinone and salvipisone may be useful in the treatment
      of human cancers, especially in the case of drug resistance.

PMID- 16989307
TI  - Antimicrobial compounds from Coleonema album (Rutaceae).
AB  - Coleonema album, a member of the South African fynbos biome, was evaluated for
      its antimicrobial activity associated with its secondary metabolites. Ethanol-
      and acetone-based extracts obtained from plants from two different geographical
      areas were analyzed. A bioassay-guided fractionation methodology was followed for
      rapid and effective screening for the presence of bioactive compounds. The TLC
      bioautographic method, used to screen the plant extracts for antimicrobial
      activity and localization of the active compounds, indicated the presence of a
      number of inhibitory compounds with activity against the microorganisms (E. coli,
      B. subtilis, E. faecalis, P. aeruginosa, S. aureus, M. smegmatis, M.
      tuberculosis, C. albicans, C. cucumerinum) tested. Evaluation of the inhibitory
      strength of each extract by the serial microdilution assay indicated that the C.
      album extracts inhibited effectively all the microorganisms, with the minimum
      inhibitory concentrations in the low mg ml(-1) range. Identification and
      structural information of the bioactive components were obtained by a combination
      of preparative TLC and LC-MS. It revealed the presence of coumarin aglycones
      which were responsible for the observed antimicrobial activities. The results of
      this study indicate that C. album possesses strong antimicrobial activity against
      a wide range of microorganisms that warrants further investigation into the use
      of the extracts or their active constituents as a potential source for novel
      drugs.

PMID- 16989308
TI  - Antimicrobial activity of extracts of chemical races of the lichen Pseudevernia
      furfuracea and their physodic acid, chloroatranorin, atranorin, and olivetoric
      acid constituents.
AB  - The antimicrobial activity and the MIC values of the ethanol, chloroform, diethyl
      ether, and acetone extracts of the chemical races of Pseudevernia furfuracea
      (var. furfuracea and var. ceratea) and their physodic acid, chloroatranorin,
      atranorin, and olivetoric acid constituents have been investigated against some
      microorganisms. Nearly all extracts of both chemical races showed antimicrobial
      activity against Aeromonas hydrophila, Bacillus cereus, Bacillus subtilis,
      Listeria monocytogenes, Proteus vulgaris, Staphylococcus aureus, Streptococcus
      faecalis, Yersinia enterocolitica, Candida albicans, Candida glabrata, Alternaria
      alternata, Ascochyta rabiei, Aspergillus niger, Fusarium culmorum, Fusarium
      moniliforme, Fusarium oxysporum, Fusarium solani, and Penicillium notatum. There
      was no antimicrobial activity of the extracts against Escherichia coli,
      Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas syringae, Salmonella
      typhimurium, Alternaria citri, Alternaria tenuissima, and Gaeumannomyces
      graminis. Chloroatranorin and olivetoric acid were active against the same
      microorganisms with few exceptions. Physodic acid was active against about the
      same bacteria and yeasts and inactive against all of the filamentous fungi
      tested. Also no activity of atranorin against the filamentous fungi was observed.

PMID- 16989309
TI  - Biologically active constituents of a polyphenol extract from Geranium sanguineum
      L. with anti-influenza activity.
AB  - From the aerial roots of the medicinal plant Geranium sanguineum L. a polyphenol
      rich extract with strong anti-influenza activity has been isolated. To
      investigate its active fractions, the extract was partitioned by solvents with
      increasing polarity. The n-BuOH fraction contained the majority of the in vitro
      antiviral activity; the EtOAc fraction was the most effective one in vivo. A
      bioassay-directed fractionation of the n-BuOH and EtOAc fractions was performed
      to obtain information about the nature of the chemical components of the plant
      extract, responsible for the antiviral effect. The individual constituents were
      identified by spectroscopic methods and comparison with authentic samples and by
      HPLC. The cell-toxic and virus-inhibitory effects of the fractions and some
      individual polyphenol compounds, found in Geranium sanguineum L., were studied
      using the replication of representative influenza viruses in cell cultures. This
      study showed that the presence of a variety of biologically active compounds as
      well as the possible synergistic interactions between them seem to be decisive
      for the overall antiviral effect.

PMID- 16989310
TI  - Radical quenching by rosmarinic acid from Lavandula vera MM cell culture.
AB  - This study was conducted to evaluate the radical scavenging capacities of
      extracts and preparations from a Lavandula vera MM plant cell culture with
      different rosmarinic acid content and to compare them with pure rosmarinic and
      caffeic acids as well. The methods, which were used are superoxide anion and 2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radicals
      scavenging assays. Results showed that extracts and preparations from Lavandula
      vera MM possess strong radical scavengers, as the best both radical scavengers
      appeared to be the fractions with enriched rosmarinic acid content, obtained
      after ethylacetate fractioning (47.7% inhibition of superoxide radicals and 14.2
      microM 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid equivalents,
      respectively). These data reveal the possibilities for application of these
      preparations as antioxidants.

PMID- 16989311
TI  - Secondary metabolites and insecticidal activity of Anemone pavonina.
AB  - The insecticidal properties of the crude extracts of the leaves and flowers of
      Anemone pavonina were evaluated on Pheidole pallidula ants and showed significant
      levels of activity. Bioassay-guided fractionations led to the isolation of the
      butenolide ranunculin (1) as the active principle. Chemical investigations of the
      extracts showed them to contain as major components the sitosterol
      glycopyranoside lipids 2-5 and the glycerides 6-8. The structures of the
      metabolites were elucidated, following acetylation and hydrolysis of the natural
      products, by interpretation of their NMR and mass spectral data. The uncommon
      lipid metabolites 2-8 were isolated for the first time from the genus Anemone and
      this is the first report of insecticidal activity of the Anemone metabolite
      ranunculin against ants.

PMID- 16989312
TI  - Anthocyanins, colour and antioxidant properties of eggplant (Solanum melongena
      L.) and violet pepper (Capsicum annuum L.) peel extracts.
AB  - Acetone extracts from eggplant (Solanum melongena L.) and violet pepper (Capsicum
      annuum L.) peels both belonging to the Solanaceae plant family were characterized
      with respect to their anthocyanin profiles, colour qualities and antioxidant
      capacities. According to HPLC-DAD-MS3 analyses the major anthocyanin in eggplant
      was delphinidin-3-rutinoside, while the predominant pigment in violet pepper was
      assigned to delphinidin-3-trans-coumaroylrutinoside-5-glucoside. Since virtually
      all anthocyanins were delphinidin-based, the effect of acylation and
      glycosylation patterns on colour stability and antioxidant capacity could be
      assessed. Application of two in vitro-assays for antioxidant capacity assessment
      revealed that eggplant generally exhibited higher values compared to violet
      pepper which was ascribed to 3,5-diglycosylated structures predominating in the
      latter. The higher extent of acylation in violet pepper was reflected by a more
      purplish colour shade of the extracts, but did not translate into a higher
      stability against fading which again was attributed to additional glycosyl
      substitution at C5. These findings support the relevance of structure-related
      activities of anthocyanins both for understanding food colour and their
      particular nutritional value.

PMID- 16989313
TI  - Structure-activity relationship of acetylenes from galls of Hedera rhombea as
      plant growth inhibitors.
AB  - The structure-activity relationship of 12 isolated acetylenes from galls of
      Hedera rhombea (Araliaceae) induced by Asphondylia sp. (Cecidomyiidae) and their
      derivatives has been studied for the inhibition of the shoot and root growth of
      rice, perennial ryegrass, cockscomb, lettuce, and cress. Almost all acetylenes
      generally showed growth inhibitory activity. The diacetylenes exhibited higher
      activity than the monoacetylenes, suggesting that a conjugated diyne segment is
      essential for the activity. On the other hand, the acetylenes with a nonoxidated
      methylene group at C-8 showed stronger activity comparing with those possessing
      hydroxy and acetoxy groups at C-8. Furthermore, it has been demonstrated that the
      acetylenes bearing a terminal olefinic group at C-16, C-17 enhanced the activity.
      It is thus clarified that important sites for the activity of the acetylenes from
      galls of H. rhombea are a conjugated diyne and a terminal olefinic group
      connecting to the aliphatic chain and that less oxidated compounds show more
      activity.

PMID- 16989314
TI  - Altered toxicities of fatty acid salts in green paramecia cultured in different
      waters.
AB  - Detergents including fatty acid salts act as surface-active agents and thus
      possibly damage the plasma membrane structures of aquatic organisms. Therefore,
      when excess, the house-used and industrial outflows of such detergents into
      aquatic environments may have considerable impacts on the ecosystem. In this
      study, we propose the use of green paramecia (Paramecium bursaria) for assessing
      the acute toxicity of eight fatty acid salts (Na and K salts of oleate,
      palmitate, laurate and myristate) under various water conditions. The Paramecium
      in the stationary phase were used for a toxicity assay carried out on 12-well
      microplates and the median lethal concentration (LC50) was determined for each
      fatty acid salt. In the low mineral culture medium prepared with ultra-pure
      water, the LC50 for each fatty acid ranged from 5.8 to 144 ppm (w/v). The toxic
      levels of fatty acid salts differed in the following order: laurate, myristate >
      or = oleate, palmitate. The toxic levels of oleate and palmitate salts were ca.
      10-fold lower than those of laurate and myristate salts. When river water and
      local tap water instead of ultra-pure water were used for culturing, the toxic
      levels of all fatty acid salts were drastically lowered compared to the low
      mineral condition by 30- to 100-fold (198-660 ppm, w/v). Similar detoxification
      effect was observed when Ca or Mg was added to the low mineral culture media,
      indicating that the toxicity of fatty acid salts can be notably lowered as the
      mineral content increases. As we demonstrated that toxicities of fatty acid salts
      can be lowered in river water and tap water compared to the low mineral
      condition, some chemical substances behave differently in the different water
      conditions. Therefore, the use of natural waters reflecting the real
      environmental conditions in further collection of data on the ecotoxicity impacts
      of variety of chemicals is highly encouraged.

PMID- 16989315
TI  - Changes of redox activity during the development of rape.
AB  - Redox activity was measured in vegetative and generative apical parts (5 mm of
      the stem) and youngest leaves of winter (cv. "G6rczanski") and spring (cv.
      "Mlochowski") rape. Both genotypes were cultured under the same growth conditions
      (17/15 degrees C day/night, 16 h photo-period), but winter rape was additionally
      vernalized (5/2 degrees C day/night, 56 days) in order to induce the generative
      development. The cyclic voltammetric method was used to measure the redox
      potential of samples in the presence of Fe3+ ions. Changes in the redox activity
      were compared with changes in riboflavin content and activities of antioxidative
      enzymes: superoxide dismutase (SOD) and catalase (CAT). The higher level of Fe3+
      ions and riboflavin detected in generative apices and leaves of winter and spring
      varieties indicated that electrons (and their donors) were present at a lower
      level in these organs in comparison with the vegetative ones. On the contrary,
      SOD and CAT activity were lower in generative than in vegetative organs. This
      confirms changes in the redox balance and involvement of oxygen radicals in the
      generative development of rape plants. The similarity of the measured parameters
      between winter and spring varieties indicates that the observed changes are
      independent of the way of generative induction (vernalization). Riboflavin can
      serve as one of the electron carriers between other oxidation-reduction
      substances.

PMID- 16989316
TI  - Production and properties of biosurfactants from a newly isolated Pseudomonas
      fluorescens HW-6 growing on hexadecane.
AB  - The newly isolated from industrial wastewater Pseudomonas fluorescens strain HW-6
      produced glycolipid biosurfactants at high concentrations (1.4-2.0 g l(-1)) when
      grown on hexadecane as a sole carbon source. Biosurfactants decreased the surface
      tension of the air/ water interface by 35 mN m(-1) and possessed a low critical
      micelle concentration value of 20 mg l(-1), which indicated high surface
      activity. They efficiently emulsified aromatic hydrocarbons, kerosene, n
      paraffins and mineral oils. Biosurfactant production contributed to a significant
      increase in cell hydrophobicity correlated with an increased growth of the strain
      on hexadecane. The results suggested that the newly isolated strain of Ps.
      fluorescens and produced glycolipid biosurfactants with effective surface and
      emulsifying properties are very promising and could find application for
      bioremediation of hydrocarbon-polluted sites.

PMID- 16989317
TI  - In vitro organogenesis and alkaloid accumulation in Datura innoxia.
AB  - The kinetics of tropane alkaloids accumulation in different organs such as roots,
      leaves, stems, flowers and seeds of Datura innoxia was investigated by GC-MS.
      Twenty-six tropane alkaloids were detected. The ester derivatives of tropine
      (3alpha-tigloyloxytropine and 3-tigloyloxy-6-hydroxytropine) are the major
      compounds. Undifferentiated callus were established from the stem explants of
      Datura innoxia using Murashige and Skoog (MS) medium supplied with 6
      benzylaminopurine (BA, 1 mg l(-10) and indole-3-acetic acid (IAA, 0.5 mg l(-1))
      in combination for 6 weeks. Callus differentiation was initiated by subculture
      onto solid MS medium, free from hormones, for more than 10 months. Initially,
      shoots were formed after four weeks from subculture. Further subculturing in
      basal MS medium without growth regulators initiated the rooting of a shooty
      callus after 6 weeks. Investigation of the alkaloid content of the unorganized
      and organized callus revealed that callus (either green or brown) yielded only
      trace amounts of alkaloids. On the other hand, re-differentiated shoots contained
      mainly scopolamine while re-differentiated roots biosynthesized hyoscyamine as
      the main alkaloid.

PMID- 16989318
TI  - The influence of auxins on the biosynthesis of isoprene derivatives in callus
      cultures of Vaccinium corymbosum var. bluecrop.
AB  - Callus cultures of Vaccinium corymbosum var. bluecrop were optimized for their
      isoprene derivatives production by supplementing Schenk-Hildebrandt (SH) medium
      with constant concentration of kinetin (2.32 microM) and two different amounts of
      selected auxins. Every auxin, except for IBA, used in 10-time higher
      concentration (2,4D, NAA, IAA, NOA) stimulated biosynthesis of beta-sitosterol
      and inhibited triterpene synthesis. Quantitative analysis of isoprene derivatives
      in callus biomass collected on the 25th day of the experiment proved that the
      analyzed callus of Vaccinium corymbosum var. bluecrop synthesized the highest
      amount of isoprene derivatives after subculturing on SH medium modified with 22.6
      microM of 2,4D and 2.32 microM of kinetin.

PMID- 16989319
TI  - Beta-carotene-rich carotenoid-protein preparation and exopolysaccharide
      production by Rhodotorula rubra GED8 grown with a yogurt starter culture.
AB  - The underlying method for obtaining a beta-carotene-rich carotenoid-protein
      preparation and exopolysaccharides is the associated cultivation of the
      carotenoid-synthesizing lactose-negative yeast strain Rhodotorula rubra GED8 with
      the yogurt starter culture (Lactobacillus bulgaricus 2-11 + Streptococcus
      thermophilus 15HA) in whey ultrafiltrate (45 g lactose/l) with a maximum
      carotenoid yield of 13.37 mg/l culture fluid on the 4.5th day. The chemical
      composition of the carotenoid-protein preparation has been identified. The
      respective carotenoid and protein content is 497.4 microg/g dry cells and 50.3%
      per dry weight, respectively. An important characteristic of the carotenoid
      composition is the high percentage (51.1%) of beta-carotene (a carotenoid pigment
      with the highest provitamin A activity) as compared to 12.9% and 33.7%,
      respectively, for the other two individual pigments--torulene and torularhodin.
      Exopolysaccharides (12.8 g/l) synthesized by the yeast and lactic acid cultures,
      identified as acid biopolymers containing 7.2% glucuronic acid, were isolated in
      the cell-free supernatant. Mannose, produced exclusively by the yeast,
      predominated in the neutral carbohydrate biopolymer component (76%). The mixed
      cultivation of R. rubra GED8 with the yogurt starter (L. bulgaricus 2-11 + S.
      thermophilus 15HA) in ultrafiltrate under conditions of intracellular production
      of maximum amount of carotenoids and exopolysaccharides synthesis enables
      combined utilization of the culture fluid from the fermentation process.

PMID- 16989320
TI  - Influence of glyphosate on flower morphogenesis and pigmentation in Petunia
      hybrida.
AB  - Glyphosate showed a remarkable effect inducing the change of flower symmetry from
      the actinomorphic to the zygomorphic type in Petunia hybrida. Glyphosate [N
      (phosphonomethyl)glycine] reduced the anthocyanin content and showed a weak
      inhibitory effect against phenylalanine ammonia-lyase (PAL) activity. L-2
      Aminooxy-3-phenylpropionic acid (APA), an inhibitor of PAL activity, reduced the
      anthocyanin content but had no effect on flower shape. Additional phenylalanine
      or trans-cinnamic acid, the intermediates of glyphosate inhibition against PAL
      activity, could not recover the change of flower shape induced by glyphosate.
      These results suggested that the reduction of PAL activity alone could not
      account for the two characteristic changes of flower symmetry and pigmentation
      induced by glyphosate. On the other hand, the results of application of
      glyphosate-related compounds suggested that the structure of glyphosate
      contributed to induce the morphological change of Petunia flower. Glyphosate may
      thus be a very useful agent in the elucidation of unresolved questions of flower
      morphogenesis and the related metabolism.

PMID- 16989321
TI  - Genomic relations among 31 species of Mammillaria haworth (Cactaceae) using
      random amplified polymorphic DNA.
AB  - Thirty-one species of Mammillaria were selected to study the molecular phylogeny
      using random amplified polymorphic DNA (RAPD) markers. High amount of mucilage
      (gelling polysaccharides) present in Mammillaria was a major obstacle in
      isolating good quality genomic DNA. The CTAB (cetyl trimethyl ammonium bromide)
      method was modified to obtain good quality genomic DNA. Twenty-two random decamer
      primers resulted in 621 bands, all of which were polymorphic. The similarity
      matrix value varied from 0.109 to 0.622 indicating wide variability among the
      studied species. The dendrogram obtained from the unweighted pair group method
      using arithmetic averages (UPGMA) analysis revealed that some of the species did
      not follow the conventional classification. The present work shows the usefulness
      of RAPD markers for genetic characterization to establish phylogenetic relations
      among Mammillaria species.

PMID- 16989322
TI  - 4-methyl-l-hepten-3-one, the defensive compound from Agathemera elegans
      (Philippi) (Phasmatidae) Insecta.
AB  - Insects of the genus Agathemera (Phasmatidae) live in the Chilean Andes over 1500
      m above sea level. On disturbing, the insects release a spray that can cause
      temporary blindness in humans. Very little is known on the composition of
      chemicals used for defense by South American phasmids. Here we show that both
      female and male defensive secretion of Agathemera elegans is made up of 4-methyl
      1-hepten-3-one. The compound is reported for the first time as a natural product.

PMID- 16989323
TI  - Overexpression of celB gene coding for beta-glucosidase from Pyrococcus furiosus
      using a baculovirus expression vector system in silkworm, Bombyx mori.
AB  - beta-Glucosidase is a member of the glycosyl hydrolases that specifically
      catalyze the hydrolysis of terminal nonreducing beta-D-glucose residues from the
      end of various oligosaccharides with the release of beta-D-glucose. CelB gene,
      encoding the thermostable beta-glucosidase, was amplified from the Pyrococcus
      furiosus genome and then cloned into the baculoviral transfer vector under the
      control of the polyhedrin gene promoter. After co-transfection with the
      genetically modified parental Bombyx mori nucleopolyhedrovirus (BmNPV), the
      recombinant virus containing celB gene was used to express beta-glucosidase in
      silkworm. The recombinant beta-glucosidase was purified to about 81% homogeneity
      in a single heat-treatment step. The optimal activity of the expressed beta
      glucosidase was obtained at pH 5.0 and about 105 degrees C; divalent cations and
      high ionic strength did not affect the activity remarkably. This suggested that
      the enzymatic characteristics of recombinant beta-glucosidase were similar to the
      native counterpart. The expressed beta-glucosidase accounted for more than 10% of
      silkworm total haemolymph proteins according to the protein quantification and
      densimeter scanning. The expression level reached 10,199.5 U per ml haemolymph
      and 19,797.4 U per silkworm larva, and the specific activity of the one-step
      purified crude enzyme was 885 U per mg. It was demonstrated to be an attractive
      approach for mass production of thermostable beta-glucosidase using this system.

PMID- 16989324
TI  - Toxicity and metabolism of the chloral-derived mammalian alkaloid 1
      trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) in PC12 cells.
AB  - Chloral-derived beta-carbolines, which are structurally similar to the
      dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 5),
      are discussed to contribute to neuronal cell death in idiopathic Parkinson's
      disease. The cytotoxicity of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline
      (TaClo, 4) to neuronal-like clonal pheochromocytoma PC12 cells was examined by
      the determination of lactate dehydrogenase (LDH) release. After incubation for 48
      h, 4 showed a strong dose-dependent cytotoxic activity towards PC12 cells with an
      ED50 value of 230 microM. In PC12 cells reductive dehalogenation of 4 was
      observed giving rise to the formation of 1-dichloromethyl-1,2,3,4-tetrahydro-beta
      carboline (6) as a main TaClo metabolite exhibiting a cytotoxic potential
      comparable to that of TaClo. An X-ray structure analysis, performed for the
      trifluoroacetyl derivative of 6, revealed the N-substituent of such a highly
      chlorinated agent to be dramatically pushed out of the beta-carboline ring
      'plane' due to the high steric demand of the huge dichloromethyl group at C(1).

PMID- 16989326
TI  - Vagus nerve stimulation for depression and other neuropsychiatric disorders.

PMID- 16989325
TI  - Kinetics of 13 new cholinesterase inhibitors.
AB  - Kinetics of hydrolysis of acetylcholine and acetylthiocholine by two types of
      acetylcholinesterase and butyrylcholinesterase inhibited by 13 new inhibitors (5
      carbamates and 8 carbazates--hydrazinium derivatives) was measured in vitro in a
      batch reactor at 25 degrees C, pH 8, ionic strength 0.11 M and enzyme activity
      3.5 U by four nondependent analytical methods. Sevin, rivastigmin (Exelon) and
      galantamin (Reminyl) served as comparative inhibiting standards. Kinetics of
      hydrolyses inhibited by all studied carbamates, sevin, carbazates (with
      exceptions) and rivastigmin (with exceptions) can be simulated by the competitive
      inhibition model with irreversible reaction between enzyme and inhibitor.
      Galantamin does not fulfil this model. In positive simulations, the value of
      inhibition (carbamoylation) rate constant k3 was calculated, describing the
      reaction velocity between the given enzyme and inhibitor. Physiologically
      important hydrolyses of acetylcholine catalyzed by acetylcholinesterase from
      electric eel or bovine erythrocytes and butyrylcholinesterase from horse plasma
      can be most quickly inhibited by carbamoylation of the mentioned enzymes by the 3
      N,N-diethylaminophenyl-N'-(1-alkyl) carbamates 4 and 5. Probably this is due to a
      long enough hydrocarbon aliphatic substituent (hexyl and octyl) on the amidic
      nitrogen atom. The tested carbazates failed as inhibitors of cholinesterases. The
      regeneration ability of the inhibited enzymes was not measured.

PMID- 16989327
TI  - The concept of attractiveness & older adults with mental illness residing in
      nursing homes.

PMID- 16989328
TI  - Web-based treatment for problem drinking.
AB  - Interest in Web-based interventions to curtail hazardous drinking has increased
      in recent years. Emerging research findings suggest that Web-based interventions
      may help reduce alcohol abuse, especially among college students and women. At
      the same time, it may be difficult for marginalized individuals and those in
      rural areas to access the Internet. Nurses are encouraged to help clients
      evaluate alcohol intervention Web sites to identify the best treatment options.
      Additional research is recommended to determine the efficacy of online alcohol
      treatment services.

PMID- 16989329
TI  - The ten commitments: a value base for mental health recovery.
AB  - The concept of recovery is an important part of contemporary mental health
      services. During the past 5 years, Tidal Model projects, focused on developing
      the recovery attitude within nursing practice, have been established in several
      different countries. The Tidal model emphasizes 10 philosophical assumptions the
      "Ten Commitments," that are central to recovery-focused practice.

PMID- 16989330
TI  - Boundaries & adolescents in residental teatment settings: what clinicians need to
      know.
AB  - Working with adolescents in psychiatric treatment settings poses unique
      challenges related to boundaries. Staff are typically from a range of
      disciplines, and some are from nonregulated professions. Three potential boundary
      crossing areas are touching, gift giving, and self-disclosure. To enhance quality
      of care, staff needs an orientation aimed at boundary education, including the
      concepts of transference and countertransference; an atmosphere of safety to
      discuss their observations of themselves and others; to be willing to provide
      feedback; and a sound knowledge base of adolescent growth and development.

PMID- 16989331
TI  - Mercury rising.

PMID- 16989332
TI  - Guess who's putting you under.

PMID- 16989333
TI  - Peddling the pomegranate.

PMID- 16989334
TI  - A NICE approach.

PMID- 16989335
TI  - Wisdom from tragedy.
AB  - Pauline Freeman's death at Eastbourne District General Hospital in 1998 sparked
      widespread publicity and an inquiry. Ms Freeman's twin sister, a former nurse,
      believes understaffing played a key part in the tragedy.

PMID- 16989336
TI  - Intimacy in nursing.
AB  - There are many definitions of intimacy in nursing but what they all have in
      common is the need for communicated empathy, for nursing that is not just caring
      for but also caring about.

PMID- 16989337
TI  - Brain training.

PMID- 16989338
TI  - New figures for total number of people with HIV in the UK.

PMID- 16989340
TI  - Guidelines for the prevention and treatment of pressure ulcers.
AB  - An 'all-in-one' guideline on pressure ulcer prevention and management in primary
      and secondary care was published last year by the National Institute for Health
      and Clinical Excellence (NICE 2005a). The guideline is published in two parts.
      The first part is The Management of Pressure Ulcers in Primary and Secondary Care
      (Royal College of Nursing (RCN) and NICE 2005). The second part concerns pressure
      ulcer risk assessment and prevention, including the use of pressure-relieving
      devices (NICE 2003). A quick reference guide (NICE 2005b) summarises the
      recommendations made in both parts and is the focus of this article.

PMID- 16989339
TI  - Concordance with antidepressant medication in primary care.
AB  - AIM: To identify how depression is managed in primary care settings and examine
      patients' perspectives on their care and the impact medication had on their
      recovery. This article specifically addresses patients' accounts of the
      influences on medication concordance. METHOD: A total of 60 patients from four
      primary care centres who had a recent episode of depression were interviewed
      using a semi-structured questionnaire and a framework analysis to identify
      recurring themes. Participants had largely recovered from their illness.
      FINDINGS: Many factors influenced patients' decisions to take and continue
      prescribed antidepressants and four broad themes were identified. These were: the
      role and relationship with health practitioners; factors related to the illness;
      beliefs about and experiences of medication for depression; and the wider context
      of depression. CONCLUSION: Concordance with antidepressants is multifactorial and
      may change over time in the same patient. Influences on concordance may be
      positive or negative and the combined effects are highly individual and dependent
      on circumstances. Nurses involved in medication management should encourage
      discussion of the likely impact of, and patients' attitudes toward, medication.

PMID- 16989342
TI  - Peripheral intravenous therapy.

PMID- 16989341
TI  - Assessment and management of surgical wounds in clinical practice.
AB  - Successful nursing care of surgical wounds is dependent on the nurse's knowledge
      and understanding of normal wound healing physiology, the type of surgery
      performed, the method of closure and the optimal treatment of the resultant
      wound. Using this knowledge, nurses can provide a systematic and holistic patient
      assessment, and consider any potential wound-related complications.

PMID- 16989343
TI  - Learning by doing.

PMID- 16989344
TI  - A cut above.

PMID- 16989345
TI  - 14 private firms win place on choice menu in pounds sterling 200m deal.

PMID- 16989346
TI  - The kids are alright, but are they ready to be governors?

PMID- 16989347
TI  - On deficit distortion.

PMID- 16989348
TI  - Progress is about perception as headlines and reality clash.

PMID- 16989349
TI  - Barometer. PCTS August 2006.

PMID- 16989350
TI  - A picture of progress.
AB  - A group of trusts in the North have banded together to develop a model based on
      13 clusters of care which allow a variety of interventions. The Information
      Centre for health and social care is collecting patient data in preparation for
      developing its own classification system. Getting staff on board is seen as vital
      for both projects.

PMID- 16989351
TI  - On mental health.

PMID- 16989352
TI  - Report calls for 'radical action' to plug Manchester health gap.

PMID- 16989353
TI  - New service to combat lack of NHS dentists.

PMID- 16989354
TI  - Care heads for the high street as Blair courts retail kings.

PMID- 16989355
TI  - On a new PCT framework.

PMID- 16989356
TI  - Why the NHS must wake up to the medical technology gap.

PMID- 16989357
TI  - Data briefing: Variations in spend on HRGs.

PMID- 16989358
TI  - How to create real sustainable change in your community.

PMID- 16989359
TI  - Scheme review. All change.

PMID- 16989360
TI  - Survey. Losing faith?

PMID- 16989361
TI  - Skills. Move with the times.
AB  - Future NHS leaders will need a wide variety of emerging skills in strategic
      leadership, HR, market management, clinical engagement and partnership. Work
      being carried out by the NHS Institute for Innovation and Improvement aims to
      embed these principles through action learning sets and leadership programmes.
      Fitness for purpose reviews, such as those recently carried out for PCT chief
      executives, are designed to assess whether leaders have the skills they need.

PMID- 16989362
TI  - Clinical leadership. Engagement party.

PMID- 16989363
TI  - Innovation. Overseas, over here?

PMID- 16989364
TI  - On isolated GPs.

PMID- 16989365
TI  - Public health. Leader of the revolution.

PMID- 16989367
TI  - Re: interview with Denis O'Mullane.

PMID- 16989366
TI  - The profession.

PMID- 16989368
TI  - Murphy's law. Interview by Paul O'Grady.

PMID- 16989369
TI  - Warning: bisphosphonates and osteochemonecrosis of the jaws.
AB  - The aim of this article is to highlight the link between bisphosphonates and
      osteonecrotic lesions of the jaws ("osteochemonecrosis") and to alert general
      practitioners to the implications these drugs may have on their day-to-day
      practice. We review the use of this class of drug, the indications for which have
      widened recently, describe their effect on bone metabolism and outline the
      proposed mechanism for bisphosphonate-induced osteochemonecrosis. Predisposing
      and initiating factors and management are outlined, and suggestions made as to
      how the dental profession can help with this increasingly prevalent problem.

PMID- 16989370
TI  - Irrigants in non-surgical endodontic treatment.
AB  - This paper highlights that one of the main goals of root canal treatment is the
      elimination of microorganisms from the contaminated root canal system.
      Instrumentation alone will not allow for adequate debridement and disinfection of
      the complex and diverse root canal system. Chemomechanical debridement is
      required. The importance of the use of irrigants during non-surgical root canal
      treatment has frequently been neglected both during instruction of dental
      students and later in the clinical practice of endodontics. The article
      highlights 'shape, clean and fill' vs. 'clean, shape and fill' to enable
      chemomechanical debridement. Our protocol advises mechanical debridement and
      copious irrigation for a minimum of twenty minutes with 2.5% to 6% solutions of
      sodium hypochlorite, followed by a rinse with a 17% solution of
      ethylenediaminetetraacetic acid and a final rinse with 2% chlorhexidine. The
      canals are dried with high volume aspirators and sterile paper points.

PMID- 16989371
TI  - Selling a dental practice?

PMID- 16989372
TI  - The longest holiday.

PMID- 16989373
TI  - Diagnosis of patients with chronic cough.

PMID- 16989374
TI  - Bronchoscopic study on aetiology of chronic cough in HIV-infected adults with
      negative sputum smears for Mycobacterium tuberculosis at Kenyatta National
      Hospital, Nairobi.
AB  - OBJECTIVE: To establish the aetiology of chronic cough in HIV-infected patients
      with negative sputum smears for Acid Fast Bacilli (AFB). DESIGN: A cross
      sectional descriptive study. SETTING: Kenyatta National Hospital, a tertiary
      referral centre in Kenya SUBJECTS: Sixty five HIV-infected adults presenting with
      chronic cough and negative sputum smears for AFBs. RESULTS: Sixty-two patients
      were included in the final analysis. Aetiology of chronic cough was established
      in 42 (68%) patients. Pneumocystis jiroveci, bacterial pneumonia and
      Mycobacterium tuberculosis were diagnosed in 22 (35.5%), 17 (27.4%) and 14
      (22.5%) patients respectively. Majority (98%) of patients with a diagnosis had
      multiple causes established in them. Ciprofloxacin had activity against 91% of
      the isolated organisms while Penicillin was active against 35% only. CONCLUSION:
      This study documents Pneumocystis jiroveci pneumonia as a common cause of
      morbidity in a subset of HIV infected patients with chronic cough and negative
      sputum smears for AFB in Kenya.

PMID- 16989375
TI  - Quality assessment of sputum smear microscopy for detection of acid fast bacilli
      in peripheral health care facilities in Dar es Salaam, Tanzania.
AB  - BACKGROUND: There is no published information regarding the quality of sputum
      smear microscopy in Tanzania. OBJECTIVE: To evaluate technical quality and
      results of smear microscopy for acid-fast bacilli (AFB) in peripheral health care
      facilities in Kinondoni and Ilala Districts in Dar es Salaam, Tanzania. DESIGN:
      Cross-sectional study. SETTING: All tuberculosis diagnostic centres in Dar es
      Salaam, Tanzania. RESULTS: The proportion of well prepared smears was 86.2% and
      that of well stained smears was 81.2%. The overall average agreement in reading
      was (89.2%). The overall sensitivity was 88.5% and specificity was 100%. High
      false negatives (HFN) were the major errors found in this study and Low false
      negative (LFN) and quantification errors (QE) were the minor errors found. There
      were no false positive errors. Minor errors occurred more frequently in hospitals
      than dispensaries, while major errors occurred more frequently in dispensaries
      than in hospitals. CONCLUSIONS: The types of errors found in this survey, HFN,
      LFN and QE, suggest a systematic under-reading of smears in all the surveyed
      health facilities, probably due to a number of technical factors (quality of
      smears, poor stains, bad microscopes, or inadequate training) and other factors
      such as overwork and lack of motivation which need to be addressed.
      RECOMMENDATIONS: Regular supervision using the new WHO quality assurance
      guidelines should be conducted countrywide. We do recommend that blind re
      checking as the most efficient means of making the first broad assessment of
      sputum smear microscopy in Tanzania.

PMID- 16989376
TI  - Socio-economic and demographic factors associated with prevalence of HIV
      infection among pregnant women in Dar es Salaam, Tanzania.
AB  - BACKGROUND: HIV/AIDS epidemic has become generalised in low resource settings in
      sub-Saharan Africa where 90% of all maternal-foetal transmission of HIV infection
      occurs. Global effort to scale-up pMTCT is underway, however, mechanisms to
      maximise screening of HIV- 1 positive women for Nevirapine treatment and other
      interventions, are not clear. OBJECTIVE: To identify socioeconomic and
      demographic characteristics associated with the prevalence of HIV- 1 infection
      among Tanzanian women. DESIGN: Cross-sectional study. SETTING: Four antenatal
      clinics in Dar es Salaam. RESULTS: HIV prevalence rate was 13.1 (95% confidence
      interval (CI): 12.7% - 13.5%) and it increased with increasing maternal age.
      Older age than 25, mid-arm circumference less than 25cm, geographic location,
      working in a public house, and partner's occupation were independently associated
      with higher prevalence of infection. Women in monogamous marriages were 77% less
      likely to be HIV infected compared to women with no regular partner. Similarly,
      women with more than five persons per household, and those who spent less on food
      had a significantly lower HIV prevalence. CONCLUSION: HIV infection is
      sufficiently widespread among women in Dar es Salaam suggesting that screening
      based on socioeconomic and demographic characteristics would miss a large
      proportion of the positives. There is need to increase facilities for counselling
      and testing using an opt-out approach for testing in all antenatal clinics in the
      city.

PMID- 16989377
TI  - Chronic suppurative otitis media in Tanzanian school children and its effects on
      hearing.
AB  - OBJECTIVES: To compare different treatment regimens of chronic suppurative otitis
      media (CSOM) in school children, in regard to their consequence in hearing and
      discharge from the ear drum perforation. DESIGN: Randomised controlled trial.
      SETTING: Randomly selected primary schools within Dar es Salaam. SUBJECTS: Three
      hundred and twenty eight children between 5-17 years of age with CSOM in one or
      both ears. RESULTS: Three to four months after the onset of treatment 31% of
      group 1, 54% of group 2, and 56% of group 3, had dry ears. Treatment with dry
      mopping and boric acid in alcohol ear drops was significantly better than dry
      mopping alone. Adding amoxicillin to the treatment did not improve the end
      results. Hearing test performed before and after treatment showed that the
      hearing thresholds were the same or better after the treatment. The possible risk
      that boric acid in alcohol ear drops should lead to sensorineural hearing loss
      has not been confirmed. CONCLUSION: Based on the above results, the treatment of
      choice for CSOM in children in Dar es Salaam should be dry mopping and boric acid
      in spirit ear drops.

PMID- 16989379
TI  - Adhesive intestinal obstruction.
AB  - BACKGROUND: Adhesions after abdominal and pelvic surgery are a major cause of
      intestinal obstruction in the western world and the pathology is steadily gaining
      prominence in our practice. OBJECTIVE: To determine the magnitude of adhesive
      intestinal obstruction; to determine the types of previous operations in patients
      who presented with adhesive intestinal obstruction; to determine the outcome of
      treatment; and to determine the factors affecting the overall management of
      adhesion-related intestinal obstruction. DESIGN: Retrospective descriptive study.
      SETTING: The Moi Teaching and Referral Hospital (MTRH) - Eldoret, Kenya. RESULTS:
      Ninety three patients were managed for adhesive intestinal obstruction. Of these,
      57 were male and 36 were female. Abdominal distension, bilious vomiting, absolute
      constipation and abdominal pain were the main symptoms. Forty two (45%) patients
      were operated on, twenty five (59%) of them being operated on more than 72 hours
      after the start of the symptoms. Eight (9%) patients had ischaemic gut injury by
      the time of operation. Fluid therapy was inadequately administered in 86 (92%)
      patients, and their charts were not completely filled. CONCLUSION: Adhesion
      related intestinal obstruction is a common problem encountered in the surgical
      service at the Moi Teaching and Referral Hospital-Eldoret. It is the major cause
      of intestinal obstruction. Fluid therapy and delayed surgical intervention were
      the major challenges in the management of these patients.

PMID- 16989378
TI  - Non-adherence to community directed treatment with ivermectin for onchocerciasis
      control in Rungwe district, southwest Tanzania.
AB  - BACKGROUND: Community directed treatment with ivermectin (CDTI) for
      onchocerciasis control was developed as a strategy for achieving sustained high
      coverage in endemic communities. This strategy for over a short period of time
      has radically altered the consequences of infection with Onchocerca volvulus. The
      present challenge is maintaining the high therapeutic coverage especially in some
      of the impoverished endemic countries. One of these challenges is non-adherence
      to ivermectin treatment and this provides compelling reason for data collection
      at community level. OBJECTIVE: To describe the factors associated with non
      adherence to CDTI. DESIGN: Cross-sectional descriptive study. SETTING:
      Communities participating in CDTI activities in Ndubi village, Rungwe district,
      southwest Tanzania. RESULTS: A high proportion (66%) of respondents were aware of
      onchocerciasis, and this was more significant in males than females (X2 = 9.17;
      p< 0.002). Knowledge on causes of the disease was low, only 29.3% associated it
      with the bite of Simulium fly, 17% associated it with mosquitoes, 17.1% to
      houseflies, and 30% had completely no idea. Knowledge on signs and symptoms of
      onchocerciasis was also observed to be equally low (20.4%) among the respondents.
      Similarly, only 35.4% of the respondents knew itching, swelling of the body,
      diarrhoea and vomiting as associated side effects of ivermectin. There was,
      however, no sex difference in knowledge levels (X2 = 0.01; p>0.939). Low
      knowledge levels on causes of the disease, signs and symptoms and side effects of
      ivermectin were attributed to inadequate health education in the communities.
      However, some other factors associated with non-adherence were local beliefs and
      the lifestyle of alcoholism. CONCLUSIONS: Factors identified to affect programme
      implementation and associated with non-adherence were inadequate knowledge on
      causes of the disease and sign/symptoms, side effects of ivermectin, local
      beliefs and lifestyle of alcoholism in the communities.

PMID- 16989380
TI  - Sildenafil in management of persistent pulmonary hypertension of the newborn:
      report of two cases.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) was described in 1969 by
      Gersomy and co-workers as persistent foetal circulation. Supra - systemic
      pulmonary artery pressures result in right to left shunting of blood through the
      ductus arteriosus and/or foramen ovale. This results from failure of the normal
      adaptation to extra uterine life of the foetal heart/lung system. The incidence
      is estimated at about 0.1-0.2% of live born infants, majority being term or post
      term. There is no race or gender related predisposition. Management was always
      difficult before the advent of nitric oxide (and now sildenafil). We report two
      newborn infants born at The Mater Hospital with perinatal asphyxia resulting
      inpersistent pulmonary hypertension that were successfully managed with
      sildenafil.

PMID- 16989382
TI  - Ureterovaginal fistula following laparoscopic assisted vaginal hysterectomy: case
      report.
AB  - Ureterovaginal fistula following laparoscopic assisted vaginal hysterectomy is
      reported. The injury was missed in the immediate post-operative period. There was
      delay in urological consultation. The patient later developed a ureterovaginal
      fistula which was repaired successfully with a ureteroneocystostomy four months
      later after the patient was seen in several hospitals. This case is reported to
      highlight one of the serious complications of laparoscopic surgery that can go
      unnoticed. The causes of ureteral injuries in laparoscopic surgery, prevention
      and management protocols are discussed.

PMID- 16989383
TI  - Concerned nurse.

PMID- 16989381
TI  - Right ectopic gestation following in vitro fertilisation: case report.
AB  - The management of ectopic gestation has in recent years transformed from the
      normally accepted laparotomy to the laparoscopic approach. The objective of this
      case report is to describe a rare occurrence of an ectopic gestation following in
      vitro fertilisation procedure. A 35-year-old para 0 + 0, presented with lower
      abdominal pain and per vaginal bleeding six weeks after an in vitro fertilisation
      was done in South Africa. The patient was admitted with severe lower abdominal
      pain and per vaginal bleeding at six weeks gestation following an in vitro
      fertilisation procedure. She had undergone an "evacuation" one-week prior to this
      episode due to an initial diagnosis of an incomplete abortion. No chorionic villi
      were reported on histology. The repeat serum BhCG was 777 mimicro/l and at
      laparoscopy a right unruptured ampullary ectopic gestation (4 cms in size) was
      evident. A right linear salpingostomy was subsequently performed
      laparoscopically. Histology confirmed the presence of tubal chorionic villi. The
      laparoscopic management of ectopic pregnancies is now regarded as the gold
      standard in many centres in the world. In this patient the ectopic pregnancy
      resulted following an intra-uterine zygote transfer, and was managed
      successfully.

PMID- 16989384
TI  - Nurses condemn IR laws.

PMID- 16989385
TI  - AIDS deaths linked to skills shortage.

PMID- 16989386
TI  - Unlicensed health workers--can we afford the risk?

PMID- 16989387
TI  - Warning: new IR and welfare laws may damage Australia's health.

PMID- 16989388
TI  - Pandemic containment and management.

PMID- 16989389
TI  - PICC innovation leads to improved health services.

PMID- 16989390
TI  - Building capacity for prevention in community nursing services.

PMID- 16989391
TI  - Reducing falls in the elderly.

PMID- 16989392
TI  - Nursing communication and casualisation of the nursing workforce.

PMID- 16989394
TI  - Strategic questioning the way to shift opinion.

PMID- 16989393
TI  - Palliative care education in primary health.

PMID- 16989395
TI  - [Case of clear cell hidradenoma with mucinous metaplasia in the forehead-
      immunohistochemical analysis of the mucin].
AB  - Mucinous metaplasia rarely develops in the non-neoplastic skin or its appendages,
      and almost exclusively confined to the genitalia, palms and soles. Similarly,
      mucinous metaplasia is quite uncommon in the cutaneous neoplasms and only few
      cases of clear cell hidradenomas and squamous cell carcinomas with mucinous
      metaplasia have been reported in the literature. Here we report a new case of
      clear cell hidradenoma with mucinous metaplasia in the forehead. Our
      immunohistochemical analysis revealed MUC5AC in the mucinous metaplastic cells of
      this tumor as in the extramammary Paget's disease, and expression of this gastric
      foveolar epithelial mucin core protein in these two neoplastic conditions seem to
      related to their common apocrine origin.

PMID- 16989396
TI  - [Factors predicting metallo-beta-lactamase-producing Acinetobacter baumannii in
      Iwate Medical University Hospital].
AB  - We conducted a decision tree analysis in which 6 isolates of metallo-beta
      lactamase (MBL) -producing Acinetobacter baumannii detected by a sodium
      mercaptoacetic acid disk method and 38 isolates of MBL nonproducing A. baumannii
      were investigated from January 2003 to December 2003 in Iwate Medical University
      Hospital. Factors predicting MBL-producing A. baumannii were analyzed from the
      clinical backgrounds such as laboratory data, therapeutic histories and bacterial
      circumstances. In the decision tree analysis, seven significant rules were found
      for predicting MBL-producing A. baumannii; previous isolation of P. aeruginosa,
      administration period of 3rd generation cephem antibiotics > 11 days, both TP <
      or = 6.9 g/dl and Hb < or = 6.3 g/dl, both administration of anticancer drugs and
      a use of respirator, TP > 6.9 g/dl, CRP > 22.7 mg/dl, both CRP 8.7 mg/dl and body
      temperature > 36.6 degrees C. Two cases, which were matched with the rule of TP >
      6.9 g/dl, were hospitalized in the same division, and their pulsed-field gel
      electrophoresis patterns were identical. In comparison with conventional
      statistical analysis, the decision tree analysis has advantages in explaining the
      tendencies and the relationships of the data. It is possible that, based on the
      rules extracted in this study, we could issue precautions in preventing
      nosocomial MBL-producing strains even in the earlier stages when the number of
      these isolates are still small.

PMID- 16989398
TI  - [Blood transfusion and consultation].
AB  - Many hospital staff, including doctors, nurses, pharmacists, etc., are engaged in
      blood transfusion practice, and various inquiries are referred to the blood
      transfusion services. In order to provide a prompt and proper reply,
      transfusionists must have a wealth of knowledge and experience concerning blood
      transfusion medicine. Q & A relating to blood transfusion can be found on the
      home page of the Japanese Society of Blood Transfusion, and these are useful
      staff resources to obtain simple information. However, we sometimes encounter
      difficult problems in the management of a patient's treatment. Three
      representative transfusion-related issues are described in this article: (1)
      blood transfusion to patients with a positive DAT; (2) emergency transfusion,
      especially in cases where unexpected antibodies are encountered; (3) management
      of platelet transfusion refractoriness. Minimum standards for the investigation
      of transfusion-related adverse reactions developed by SHOT (Serious Hazards of
      Transfusion) are also introduced in this article, and these have a highly
      practical value. Finally, the importance of education in transfusion medicine is
      described. The number of doctors in Japan who are engaged exclusively in
      transfusion medicine is small, but blood transfusions are performed in every
      hospital, regardless of whether such a specialist is present. We have recently
      had to deal with a wide range of transplantation-related issues. Therefore, there
      is a great need for special education in transfusion medicine for doctors in the
      transplantation and cell therapy age.

PMID- 16989397
TI  - [Analysis of the macrolide resistance gene in penicillin-resistant Streptococcus
      pneumoniae].
AB  - We examined the penicillin and macrolide resistance of 496 strains of
      Streptococcus pneumoniae (S. pneumoniae) isolated at Showa University Hospital
      from November 2004 to May 2005. According to the classification established by
      the Clinical and Laboratory Standards Institute, the ratio of penicillin
      susceptible S. pneumoniae (PSSP) was 25.8%, penicillin intermediate S. pneumoniae
      was 35.9% and penicillin resistant S. pneumoniae (PRSP) was 38.3%. The ratios of
      macrolide resistant S. pneumoniae were 85.3% for erythromycin and 76.2% for
      clarithromycin. S. pneumoniae strains were isolated mainly from pediatric
      patients, and the ratios of PRSP were similar between outpatients (39.8%) and
      inpatients (45.6%). We screened for mutations in pbp1a, pbp2b and pbp2x, and the
      retention rate of the macrolide resistance genes, ermB and mefA in 90 strains
      isolated in the same period. Seventy two strains had at least one mutation in the
      pbp genes. Interestingly, some of the penicillin susceptible strains had one or
      two pbp mutations, suggesting a progressive genetic acquirement of penicillin
      resistance. In screening for retention of the macrolide resistance genes, we
      found that 42 strains(46.7%) had ermB, 19 strains (21.1%) had mefA and 13 strains
      (14.4%) had both ermB and mefA. The possession of resistance genes and the
      minimal inhibitory concentration indicate that the resistance to erythromycin and
      clarithromycin were induced by ermB or mefA, and the resistance to clindamycin
      was induced only by ermB. Among the 72 strains with pbps mutations, 65 strains
      (90.3%) had ermB or mefA or both. Together, these results show that the strains
      with pbp mutations were being selected and, after acquiring the macrolide
      resistance gene, transform to multidrug resistant S. pneumoniae.

PMID- 16989399
TI  - [My hope for the future of the medical scientist--to the medical doctor of
      clinical laboratory medicine from internal medicine].
AB  - This is the essence of my last lecture to the medical students of Hiroshima
      University. My 38-year career as a medical school teacher can be sectioned three
      parts. My main four studies are shown at the third part. 1) We advocated
      respiratory physiologic-chemistry based on the relationships between pulmonary
      function and the constitutive chemical components of lungs. 2) We proved the
      mechanisms of hypertension at the molecular level by renin-angiotensin-adrenaline
      theory. 3) We showed the difference of mitochondria DNA in Diabetes Mellitus
      patients between Japanese and Chinese. 4) We suggested the necessity of
      standardization and holding common national reference values of main clinical
      laboratory tests by reporting our data. I am delighted that the very good studies
      of my colleagues achieved 500 IFs and express my gratitude for my colleagues'
      cooperation.

PMID- 16989400
TI  - [Contribution of medical technologists in team medical care of diabetics].
AB  - For the effective treatment of diabetic mellitus (DM), patients are encouraged to
      self-manage their disease according to the doctor's instructions and advice from
      certified diabetes educators (CDE) and other comedical staff. Therefore, the
      cooperation of medical staff consisting of a doctor, CDE, nurse, pharmacist,
      dietitian, and medical technologist is important for DM education. Medical
      technologists licensed for CDE (MT-CDE) have been participating in the DM
      education team in Kobe University Hospital since 2000. MT-CDE are in charge of
      classes for medical tests, guidance for self-monitoring of blood glucose and
      teaching how to read the fluctuation graph of the blood glucose level in the
      education program for hospitalized DM patients. MT-CDEs teach at the bedside how
      to read the results of medical tests during the first few days of hospitalization
      using pamphlets for medical tests. The pamphlets are made comprehensible for
      patients by using graphics and photographs as much as possible. It is important
      to create a friendly atmosphere and answer frank questions from patients, since
      they often feel stress when having medical tests at the early stage of
      hospitalization. This process of questions and answers promotes their
      understanding of medical tests, and seems to reduce their anxiety about having
      tests. We repeatedly evaluate their level of understanding during
      hospitalization. By showing them the fluctuation graph of the glucose level,
      patients can easily understand the status of their DM. When prescriptions are
      written on the graph, their therapeutic effects are more comprehensible for the
      patients. The items written on the graph are chosen to meet the level of
      understanding of each patient to promote their motivation. In summary, the
      introduction of MT-CDE has been successful in the education program for DM
      patients in our hospital. We plan to utilize the skills and knowledge of MT-CDE
      more in our program so that our DM education program will help patients cope with
      life with DM.

PMID- 16989401
TI  - [Role of medical technologists in the infection control team].
AB  - The infection control team (ICT) plays important roles in many different aspects
      of infection control. They include (1) surveillance for hospital-acquired
      infection, (2) developing the infection control manual, (3) checking that the
      manual is followed correctly, (4) giving information about the isolation of
      microorganisms in the hospital, (5) educating and instructing medical staff, etc.
      Many data have been accumulated on a database in the microbiology laboratory.
      Bacterial samples are also examined in the microbiological laboratory therefore
      medical technologists will be the first to notice hospital-acquired infection.
      Offering prompt information, obtained by surveillance or routine work, greatly
      contributes to infection control. Furthermore, a 24hr system for the
      microbiological laboratory may prevent occupational infection of health care
      workers. The role of the medical technologist in ICT is thus important. To
      prevent outbreaks of infection, the regional network is also important for the
      collection of information about the pathogen and the susceptibility of
      antimicrobial agents in the region. The medical technologist should participate
      in and communicate with this network. As mentioned above, the inclusion of
      medical technologists in infection control practice is essential. To participate
      in the ICT, medical technologists need to have communication skills, and be
      recognized by other team members as an essential member.

PMID- 16989402
TI  - [Role of a medical technologist in a nutrition support team].
AB  - The nutrition support team (NST) in our hospital not only develops clinical
      nutritional methods in inpatients but also performs the entire nutritional
      management including nutritional prescription in consultation with the physician
      in charge. In NST activity, clinical technologists have opportunities to report
      information on laboratory examination values obtained in daily work and make
      proposals. These opportunities are useful not only for enhancing the awareness of
      technologists who have focused on specific duties but also for training medical
      technologists. We hope that medical technologists participate in NST activity as
      full medical staff members in many institutions.

PMID- 16989403
TI  - [Problems of lung function testing in the laboratory].
AB  - Spirometry is indispensable for the screening test of general respiratory
      function, and measurements of lung volume and diffusing capacity play an
      important role in the assessment of disease severity, functional disability,
      disease activity and response to treatment. Pulmonary function testing requires
      cooperation between the subjects and the examiner, and the results obtained
      depend on technical as well as personal factors. In order to diminish the
      variability of results and improve measurement accuracy, the Japan Respiratory
      Society published the first guidelines on the standardization of spirometry and
      diffusing capacity for both technical and clinical staff in 2004. It is therefore
      essential to distribute the guidelines to both laboratory personnel and general
      physicians. Furthermore, training workshops are mandatory to improve their
      understanding of the basics of lung function testing. Recently, there has been
      increasing interest in noninvasive methods of lung function testing without
      requiring the patient's cooperation during spontaneous breathing. Three
      alternative techniques, i.e. the negative expiratory pressure (NEP) method to
      detect expiratory flow limitation, impulse oscillation system (IOS) to measure
      respiratory system resistance (Rrs) and reactance (Xrs), and interruption
      resistance (Rint) to measure respiratory resistance have been introduced. Further
      study is required to determine the advantage of these methods.

PMID- 16989404
TI  - [Evaluation of autonomic function using posture change].
AB  - There are several examinations to evaluate cardiac autonomic function. Autonomic
      neuropathy is a common complication of diabetes mellitus and is associated with
      increased mortality. Baroreflex sensitivity (BRS) is a marker for the ability to
      augment vagal activity. Several studies have shown that BRS is impaired in
      diabetes with autonomic neuropathy. The head-up tilt test is the most useful tool
      to diagnose the neurally mediated syncope. We have developed a new non-invasive
      method to evaluate the baroreflex using downward tilting (DT-BRS). In our
      previous study conducted in healthy volunteers and diabetic patients, we
      demonstrated a strong correlation between systolic blood pressure increase and
      corresponding RR interval lengthening during downward tilting, which yielded DT
      BRS values that correlated well with the BRS value obtained by the phenylephrine
      method (Phe-BRS). Heart rate responses observed after both squatting and standing
      (squatting test) are assumed to be a simple and useful tool to assess autonomic
      activity. We reported that indices of the squatting test showed a significant
      correlation with BRS assessed by Phe-BRS in diabetes. DT-BRS and the squatting
      test may provide promising information for the assessment of reflex vagal
      activity in diabetes.

PMID- 16989405
TI  - [Development of 64-channel magnetocardiography and clinical application].
AB  - A magnetocardiogram (MCG) can detect three-dimensional electric phenomena of the
      heart, because MCG does not influence the lung and torso form of the internal
      organs. In this symposium, we report the application of 64-channel MCG for the
      measurement of various arrhythmias (atrial flutter, atrial fibrillation),
      myocardial injury, and fetus arrhythmia. We composed function images of the
      conduction wave front and injured myocardium superimposed on a three-dimensional
      heart outline from the magnetic field. The injured myocardium was determined by a
      three-dimensional RT dispersion map. This algorithm allows the non-invasive
      determination of the space location of signal source and injured myocardium. In
      addition, 64-channel MCG can detect the fetal arrhythmias and autonomic nervous
      activity, which allows the diagnosis of fetus arrhythmia in detail before birth.
      Thus, MCG measurement is a useful non-invasive diagnostics procedure. However,
      there are several problems such as sealed room installation and the use of liquid
      helium. In the future, a newer technology that does not require liquid helium and
      a sealed room will be necessory.

PMID- 16989406
TI  - [Standardization and issues of rheumatoid factor measurement].
AB  - OBJECTIVES: To disclose the current situation of rheumatoid factor (RF)
      measurement in Japan. METHOD: A small-scale survey was performed among members of
      the committee for the improvement of RF measurement in 2003 using manufacturers'
      RF reference materials valued based on WHO RF reference and pooled sera. A
      nationwide questionnaire survey was also performed. Questionnaires were sent to
      356 educational institutes certified by the Japan College of Rheumatology in
      December 2004. RESULTS: The small-scale survey showed inter-laboratory
      differences of measured RF values, especially using RF references, and less in
      pooled sera. In the questionnaire survey (187 responses, recovery, 53%),
      qualitative or semi-quantitative RF measurement methods were used in a small
      number of institutes and quantitative methods were used in large numbers of
      institutes, the latex immunoassay (turbidimetric or nepherometric) was
      predominantly employed. The measuring instruments were various. The upper limit
      of the reference interval was distributed widely from 5 IU/ml to 40 IU/ml,
      indicating obvious inter-laboratory differences in RF measurement. Many
      institutes used the reference intervals recommended by the manufacturers.
      CONCLUSION: There are remarkable inter-laboratory differences in RF measurement.
      Clearly, one of the major issues is the lack of reference materials. We therefore
      need to establish a reference material of RF, even if it is a temporary one.
      Scientific societies (Japan College of Rheumatology and Japanese Society of
      Laboratory Medicine) and manufacturers providing RF measurement reagents should
      work together for the improvement of RF measurement.

PMID- 16989407
TI  - [Immunologic laboratory testing in clinical practice for rheumatoid arthritis].
AB  - The recent clinical practices for rheumatoid arthritis have changed greatly.
      First, biologic agents such as tumor necrosis factor blocker have been developed
      as well as disease-modifying antirheumatic drugs, with great efficacy in
      intractable RA. On the other hand, the importance of early effective therapeutic
      intervention has been recognized since early treatment prevents the progression
      of joint damage. However, early diagnosis of RA is not so easy because of the
      lack of appropriate diagnostic criteria. New laboratory tests have appeared for
      the diagnosis and prognostic prediction of RA. Among them, anticyclic
      citrullinated peptide antibodies (anti-CCP), which bind epitopes containing
      citrulline, seem to be attracting the most attention. Although rheumatoid factor
      (RF) is the only serologic marker among the seven classification criteria of the
      American College of Rheumatology (ACR) for RA, variability of the RF assay within
      laboratories and/or between laboratories, and quality assurance has not been
      established. We must address the standardization of RF assay as soon as possible.

PMID- 16989408
TI  - [Role of clinical data in NST: from the viewpoint of the clinical laboratory].
AB  - Serum albumin (Alb) sampling is used for patients who object to screening by NST.
      As Alb is decreased by malnutrition, it is available for nutritional assessment,
      reflecting the long-term nutritive condition. Recently, Alb was correlated with
      nutritional assessment proteins with RTP, like RBP, TTR and Tf. We recently set
      up a screening line of Alb < or =3.0g/dl; however, we will gradually elevate it
      to < or =3.5g/dl. The role of the medical technologist is to estimate the number
      of patients with < or =3.5g/dl, and investigate correlations between the Alb
      concentration and other markers, including ChE, TTR, TP and CRP.

PMID- 16989409
TI  - Taking the lead in education.

PMID- 16989410
TI  - Introducing interprofessional learning.

PMID- 16989411
TI  - It's been an education.

PMID- 16989412
TI  - Fit for practice: preparing student midwives.

PMID- 16989413
TI  - On reflection: self-assessment in learning.

PMID- 16989414
TI  - Training programmes: short and sweet?

PMID- 16989415
TI  - A special learning experience.

PMID- 16989416
TI  - Caesarean section for non-medical reasons at term.

PMID- 16989417
TI  - NICE's new postnatal guidelines recommend the implementation of UNICEF's Baby
      Friendly Initiative.

PMID- 16989418
TI  - Women, wizards and patchwork quilts.

PMID- 16989419
TI  - We never thought it would come to this.

PMID- 16989420
TI  - [Diagnosis and therapy of Rhodococcus equi infection in the horse].
AB  - Infection with Rhodococcus equi is an important cause of pneumonia in foals, but
      other organ systems may also be affected. The intracellular presence of R. equi
      and the formation of granulomatous and suppurative inflammatory tissue mean that
      prolonged treatment is needed. The pharmacological properties of the combination
      of erythromycin and rifampicin have improved the survival of foals infected with
      R. equi; however, erythromycin can cause adverse reactions in foals and mares,
      which has prompted the search for alternative therapies. The combination of
      azithromycin or clarithromycin with rifampicin seems to be a promising
      alternative. However these combinations are expensive and adverse effects remain
      to be determined, especially in the dams of treated foals. Thus correct diagnosis
      and appropriate use of drugs are essential for the treatment of R. equi infection
      in foals.

PMID- 16989421
TI  - [Vertebral osteomyelitis caused by Rhodococcus equi in a three-and-half-month-old
      Dutch Warmblood foal].
AB  - Rhodococcus equi infection occurs worldwide and is especially a problem in foals,
      where it often causes colitis or pneumonia. Other organs are seldom affected, and
      their involvement is regarded as a complication of pneumonia and/or colitis.
      Vertebral osteomyelitis is one such rare complication and is probably caused by
      haematogenous spread from inflammatory lesions in the lungs and/or intestine. In
      rare cases, osteomyelitis can be caused by contamination of a wound. This case
      study describes a foal with vertebral osteomyelitis due to R. equi in which there
      were only minor inflammatory changes in a mesenteric lymph node.

PMID- 16989422
TI  - [Researching the influence of animal feed in dogs with a congenital porto
      systemic shunt].

PMID- 16989423
TI  - [Deworming according to European standards (ESCCAP)].

PMID- 16989424
TI  - [Don't mess with furosemide].

PMID- 16989425
TI  - [Professional integrity for veterinarians].

PMID- 16989426
TI  - [It's a different way, studying in the U.S.A].

PMID- 16989427
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Cato 3].

PMID- 16989428
TI  - [Is a busy practice a profitable practice?].

PMID- 16989429
TI  - [Reaction to a letter sent by Mr. R.F. Bergsma].

PMID- 16989430
TI  - A significant anniversary.

PMID- 16989431
TI  - The freedom of mobility.

PMID- 16989432
TI  - Teaching a basic function.

PMID- 16989433
TI  - Addressing an urgent need.

PMID- 16989434
TI  - Shoulder rehabilitation.

PMID- 16989435
TI  - CPM's therapeutic benefits.

PMID- 16989436
TI  - REITs: A growing health care financing option.

PMID- 16989438
TI  - [Directional preponderance of nystagmus].
AB  - The presence of directional preponderance in the peripheral and central
      vestibular disorders and the relation of its phenomenon to the definitive
      etiological factors, spontaneous nystagmus, positional nystagmus and the role of
      lateralization of directional preponderance were described. Directional
      preponderance is helpful to distinguish between peripheral and central lesions.
      The direction of this phenomenon is significant in the supratentorial CNS
      disturbances. In the peripheral lesions it is possible to estimate the
      progression of the disease. The coexistence of the directional preponderance,
      spontaneous nystagmus and positional nystagmus has the diagnostic value in
      neurootology.

PMID- 16989437
TI  - In-vitro investigations evaluating the detection spectrum of cervical lymph nodes
      via handheld gamma probe.
AB  - BACKGROUND: Currently the significance of the sentinel node (SN) biopsy also for
      head and neck cancer is discussed intensively. Based on the complex anatomic
      structures of this region with a low distance between primary and sentinel node
      as well as approximately 300 lymph nodes an intensive discussion of the
      methodical basis of sentinel node detection seems to be essential. Thus it was
      the aim of the present study to examine the detection spectrum of a gamma probe
      for identification of cervical lymph nodes using an in vitro model to describe
      and objectify the particularities of measurement existing in the head and neck
      region. MATERIAL/METHODS: In an in vitro model the detection spectrum of a gamma
      probe is examined in 29 different series of measurements (variation of the
      specimen filled with 99m pertechnetat regarding activity, position, collimator
      distance, tissue sheath). RESULTS: The presented in vitro model reflects the
      clinical problem of narrow intranodal activity of neighbouring lymph nodes and
      reveals a direct relation between the number of radiation sources and their
      isolated evidence. Using muscle tissue with a thickness of 0.4 cm, two two-rowed
      radiation sources, the more powerful is placed 1.5 cm behind the other specimen,
      with a lateral difference of 3 cm, can be resolved only with a maximal detector
      distance of 1 cm. Not the difference of the tissue but the thickness of the
      tissue is decisive for detection. CONCLUSION: Especially for pharyngeal and
      laryngeal lymph nodes a transcutaneous measurement reflecting the exact
      localisation of hot nodes in the area of the deep jugular lymph nodes is not
      possible with increasing tissue thickness. The described results require a
      critical discussion of the different detection techniques varying among the
      different working groups of this field.

PMID- 16989439
TI  - [Hypopharyngeal Zenker's diverticulum as a clinical and surgical problem].
AB  - One of the dysphagia causes may be pharyngeal or esophageal diverticula.
      Pharyngeal diverticulum (Zenker's diverticulum) is the most common among all
      upper digestive tract diverticula. It results from protrusion of the pharyngeal
      mucosa in Killian's area (triangle), at the border of two parts of the inferior
      pharyngeal constrictor muscle. Patients with Zenker's diverticulum complain about
      different types of dysphagia as a result of retention of freshly ingested food in
      diverticulum and its regurgitation. This problem may be present for years and has
      a progressive nature. The diagnosis of Zenker's diverticulum is based on
      anamnesis and radiological examinations with applied contrast medium of the upper
      digestive tract. There are two methods of the treatment: diverticulectomy from
      external cervical approach and endoscopic (with surgical laser) incision of the
      wall between diverticulum and pharynx or esophagus. Treatment results and number
      of postsurgical complications are similar for both methods. Treatment of Zenker's
      diverticulum is in field of interest of surgeons as well as otolaryngologists.
      Location of disease in the neck and in the upper digestive tract should make us
      well acquainted with this problem.

PMID- 16989440
TI  - [Glomus caroticum, jugulare and vagale--problems in diagnosis and treatment].
AB  - INTRODUCTION: The paraganglia tissue in 80% is located in suprarenal glands. The
      rest (20%) are with close association with autonomic nerves and some cranial
      nerves. Paraganglioma, being tumors arising from the paraganglion cells of the
      parasympathetic system, were first reported in man in 1935. Although
      histologically these tumors have been shown to contain neurosecretory granules,
      they are rarely functional. There are four kinds of paragangliomas: deriving from
      carotid artery baroreceptors (glomus caroticum), internal jugular vein (glomus
      jugulare); placed along vagal nerve (glomus vagale) and paragangliomas of
      tympanic cavity (glomus tympanicum). The first three of them are clinically
      recognized as tumor of the neck. MATERIAL AND METHODS: Authors present group of 7
      patients with paragangliomas treated in ENT Department in Poznan in the years
      1994-2004. There were treated 4 patients with glomus caroticum, two with glomus
      vagale and one patient with glomus jugulare. RESULTS: All patients were treated
      surgically. In one case in group with glomus caroticum in histological
      examination tendency to infiltration of internal carotid artery was stated
      (chemodectoma malignum). The tumor was removed totally with partial excision of
      communis, external and internal carotid artery. The internal carotid artery was
      closed by the tumor. CONCLUSION: Authors underline three aspects of process of
      treatment in whole group of patients: diagnostic problems, way of treatment and
      long term results.

PMID- 16989441
TI  - [The histo-clinical analysis of 95 malignant neoplasms of parotid gland].
AB  - INTRODUCTION: Malignant tumors constituted 25% of all gland tumors, the most
      frequently in parotid gland. MATERIAL AND METHODS: The study is analysis of 436
      patients with parotid gland tumors who underwent surgery in ENT Department. The
      results of histopatological diagnosis are presented. We analysed surgical
      treatment, intraoperative tumor stage and accuracy of fine - needle aspiration
      cytology in diagnosis. RESULTS: Malignant tumors constituted 22% of all gland
      tumors. Mucoepidermoid (27%) and adenoid cyst (22%) carcinomas were the most
      common malignant tumor. Tumor stage T3-T4 was in 88,5% cases. Accuracy of fine
      needle aspiration cytology in diagnosis of parotid tumors is 81,2%.

PMID- 16989442
TI  - [Deep lobe of parotid gland tumors].
AB  - INTRODUCTION: Surgery of the parotid gland tumors can be difficult because of the
      presence of the facial nerve branches in the parotid tissue. The aim of the
      surgical treatment is complete removal of the tumor without damaging the facial
      nerve. There are several surgical techniques to expose the main trunk and the
      branches of the facial nerve. On the other hand during the surgery the nerve
      function is continuously observed by using facial nerve monitor. MATERIAL AND
      METHODS: In the years of 2002-2004 208 patients with the parotid gland tumors
      were treated. There were 177 benign and 31 malignant tumors. 159 tumors were
      located in the superficial lobe of the parotid gland, 35 in the superficial and
      the deep lobe, and 14 only in the deep lobe. All patients were treated
      surgically. RESULTS: In cases concerning the operations of the tumors located in
      the deep lobe, the facial nerve branches had to be exposed with help of the
      microscopic operating techniques. All tumors were removed totally. A paralysis of
      the facial nerve was observed in two cases of the pleomorhic adenoma with a
      diameter over 6 cm, and in 9 cases of malignant tumors of the superficial and the
      deep lobe, where the main trunk or the branches of the facial nerve were
      integrated with the tumor mass. CONCLUSION: Surgical treatment of the parotid
      gland tumors presented in our study demonstrates good results. The risk of facial
      nerve paresis is higher in malignant tumors and big pleomorphic adenomas.

PMID- 16989443
TI  - [Interleukin-10 in laryngeal cancer patients treated by surgery or radiotherapy].
AB  - INTRODUCTION: The early detection and right monitoring of the laryngeal cancer
      make a better chance of recovery. Therefore factors that might be showing the
      presence of neoplastic process are constantly being looked for. The detection of
      correlation between incidence of cancer and immunity system disorders makes us
      look for and try to answer an important question: are there any factors that
      might be cancer markers in immunity system? Cytokines are molecules that regulate
      the process of differentiation and proliferation. They are also the mediators of
      immunological and inflammatory reactions. Interleukina-10 (IL-10) is a cytokine
      that has various important functions stimulating immunity processes. IL-10 is a
      factor stimulating killer cells/cytoxic lymphocytes/ and is able to kill cancer
      cells growth spontaneously. It has been detected that some cancer cells can
      produce some IL-10, too. The aim of the study was to evaluate the serum level
      concentration of IL-10 in the laryngeal cancer patients before any medical
      treatment and its denotation after surgery or radiotherapy. MATERIAL AND METHODS:
      A group of 43 male patients with laryngeal cancer was considered for the purpose
      of this study. 22 patients were treated by surgery and 21 by radiotherapy. In all
      the cases the serum concentration of IL-10 before the treatment, in the first and
      30th days after therapy was evaluated. The results were compared with the group
      of 20 healthy volunteers. RESULTS: The mean value of IL-10 concentration in
      laryngeal cancer patients treated by surgery was 14.0 pg/ml before treatment,
      12.8 pg/ml in the 1 day and 14.4 pg/ml 30 days after the therapy. IL-10
      concentrations in patients treated by radiotherapy were respectively: 15.4, 14.4
      and 15.9 pg/ml. The mean value of IL-10 in the control group was 4.9 pg/ml. The
      serum concentrations of IL-10 in the laryngeal cancer patients were significantly
      higher than in the control group. These IL-10 concentrations didn't change
      significantly after the surgery or radiotherapy. CONCLUSION: The serum
      concentration of IL-10 in the laryngeal cancer patients is significantly higher
      than in the healthy control group. The changes of serum concentrations after the
      surgery or radiotherapy of laryngeal cancer patients are not significant and
      characteristic.

PMID- 16989444
TI  - [Interleukin 2 concentration changes in the laryngeal cancer patients during the
      surgical treatment].
AB  - INTRODUCTION: Cytokines are molecules that regulate the process of
      differentiation and proliferation. They are also the mediators of immunological
      and inflammatory reactions. One of the cytokines that participates in
      immunological processes is interleukine-2 (IL-2), whose participation in
      neoplastic processes has been proved in many researches. It's anticancer effect
      is an indirect one and is connected with stimulating processes of immunologically
      competent cells, which are cytotoxic for cancer cells. IL-2 is produced by T
      helper lymphocytes (THL), and on the basis of feedback it stimulates those
      lymphocytes to new cells and other cytokines, which stimulate next immunity cells
      or kill the cancer cells, production. The aim of the study was to evaluate the
      serum level concentration of IL-2 in the laryngeal cancer patients before any
      medical treatment and its denotation after the surgical procedure. MATERIAL AND
      METHODS: A group of 22 male patients with laryngeal cancer was considered for the
      purpose of this study. All of them were treated by surgery. In all the cases the
      serum concentration of IL-2 before the treatment, in the first and 30th day after
      therapy was evaluated. The results were compared with the group of 20 healthy
      volunteers. RESULTS: The mean value of IL-2 concentration in laryngeal cancer
      patients treated by surgery was 23.4 pg/ml before treatment, increased to 37.8
      pg/ml in the 1 day and to 54.3 pg/ml 30 days after the therapy. The serum
      concentrations of IL-2 in the laryngeal cancer patients were lower than in the
      control group before the surgical treatment. These IL-2 concentrations increased
      significantly after the surgery and 1 month after the treatment were higher than
      in the healthy population. CONCLUSION: The serum concentration of IL-2 in the
      laryngeal cancer patients treated by surgery is lower than in the healthy control
      group. IL-2 increased significantly after the surgery to higher levels than in
      the control healthy group.

PMID- 16989445
TI  - [Glottis morphology after supracricoid laryngectomy with CHP or CHEP-
      protetective and respiratory function assessement].
AB  - The aim of this study was to evaluate morphology and assess of the protective and
      respiratory function of larynx after cricohyopexis (CHP) and
      cricohyoepiglottopexis (CHEP). The examined group consisted of 58 patients (49
      males and 9 female) operated between 1984-2002. An average age 54 (min. 36, max.
      67). 32 patients underwent CHP and 26 had CHEP. CHP was performed in following
      modes: a) 1 aryteroid cartilage left in 17 (43,75%) cases, b) 2 aryteroid
      cartilages left in 14 (43,75%) cases and c) 1 aryteroid cartilage left and second
      resected with subsequent reconstruction in 1 (3,31%) case. In CHEP patients the
      operations were a) 17 (65,38%), b) 4 (15,38%) and c) 5 (19,23%) respectively. The
      aryteroid cartilage was reconstructed in 19 cases (8 after CHP and 11 after
      CHEP). In the reconstruction of aryteroid cartilage vascularized thyroid lobe was
      used in 8 cases (6 after CHP and 2 after CHEP), cuneiform or corniculate
      cartilage was used in 4 patients (1 CHP and 3 CHEP) and mucous membrane in 7
      cases (1 CHP and 6 CHEP). To determine morphology of larynx, videolaryngoscopy
      was done. Thus examination distinguished 5 neoglottis shapes: oval (62,1%),
      longitudinal (13,8), triangle (8,6%), irregular (6,9%). In 8,6% cases the
      neoglottis was invisible. Decaniulation was possible in 66% patients, 24 (75%)
      after CHP and 14 (54%) after CHEP. In the group with both aryteroid cartilages
      left, 16 (89%) patients were decannulated. 31 (54%) patients complained about
      occasional liquid aspiration. To evaluate dysphagia, subjective complaints
      between 6-12, 12-18 and >18 months after surgery were analyzed. The swallowing
      was improving in the course of time. Between 6 and 12 months after surgery 31
      (54%) subjects developed dysphagia, but after 18 months only 3 (5,1%) complained
      about swallowing impairment. Patients without aryteroid cartilage reconstruction
      or decanulated had more efficient swallowing.

PMID- 16989446
TI  - [The role of a psychologist in a rehabilitation of the patients with laryngeal
      cancer after total laryngectomy with implantation of the voice prostheses].
AB  - The new possibilities of voice rehabilitation in patients with laryngeal cancer
      who undergo total laryngectomy have been opened with the surgical insertion of
      voice prostheses after performing of the tracheoesophageal shunt. This method
      enables to achieve a voice of better quality which leads to improved patients'
      general well-being. The cornerstone of the rehabilitation after an implantation
      of voice prosthesis is an appropriate psychosocial attitude of a patient towards
      combating of a cancer and his motivation for a verbal communication. In this
      review we have characterized both a role of the psychologist in the diagnostic
      and therapeutic team and psychological attitudes of the patients with cancer.
      These problems were illustrated by the clinical cases.

PMID- 16989447
TI  - [Surgical treatment of laryngomalacia in children].
AB  - INTRODUCTION: Laryngomalacia is the most common congenital malformation of the
      larynx which causes stridor in newborns and infants. The stridor is inspiratory
      and it is first noted at birth but sometimes may not develop until 2 weeks of
      age. It increases in severity during crying, nursing, agitation, excitement and
      is made worse with head flexion or supination. Other symptoms such as
      supraclavicular, intraclavicular, intercostal and abdominal retractions may be
      associated. Boys are affected over twice as often as girls. Diagnosis of
      laryngomalacia is made by rigid or flexible laryngoscopy. Although this disorder
      is usually self-limited, in some cases the symptoms are so severe that operative
      intervention cannot be avoided. MATERIAL AND METHODS: Between 2002 and 2005, 13
      infants were operated for severe form of laryngomalacia in the Pediatric ENT Dept
      in Poznan. In all patients the rigid or flexible laryngoscopy was performed to
      confirm the diagnosis. Then aryepiglottoplasty or epiglottoplasty were performed
      in all cases. It involved excision of the redundant mucosa over the arytenoid
      cartilages, the offending parts of he aryepiglottic folds, and trimming the
      lateral edges of the epiglottis, using microlaryngeal scissors and forceps.
      RESULTS: In all children symptoms such as: laryngeal stridor, feeding
      difficulties and dyspnea improved or completely resolved. In one case post
      operative ventilation for several hours was required. All patients except one
      demonstrated significant airway improvement in the immediate postoperative
      period. CONCLUSIONS: Direct laryngoscopy must be performed prior to the
      aryepiglottoplasty to decide what amount of tissue to resect. Endoscopic
      aryepiglottoplasty with use of microlaryngeal instruments is an effective and
      safe method of the treatment of severe form of laryngomalacia. It is better to
      perform this procedure in general anesthesia without intubation.

PMID- 16989448
TI  - [Wegener's granulomatosis--diagnostic problem].
AB  - Wegener's granulomatosis there is a small--and middle--vessels vasculitis. The
      pathomorphological diagnostic criteria is known as Wegener's triad: 1)
      necrotizing granlomatous inflammation of upper and/or lower respiratory tract, 2)
      systemic or focal necrotizing vasculitis involving arteries and vein, and 3)
      focal segmental necrotizing crescentic gromerulonephritis. According to the
      current theory of pathogenesis of Wegener's granulomatosis, Staphylococcus aureus
      is involved. The rise in ANCA level during vascular inflammation is very
      important for monitoring disease. The main localization of Wagener's
      granulomatosis is in lung, nasal sinusites, nose, kidneys and nasal pharynx.
      MATERIAL AND METHODS: The history of 60-years old female patient who was being
      treated in Department of Otolaryngology for chronic bilateral otitis media for
      many years is presented. During hospitalization the sinusites, rhinitis and renal
      failure additionally were found. The CT sinuses and head, histopatological and
      ANCA exam in patient were performed. RESULTS: Based on clinical, physical,
      additional exam Wegener's granulomatosis was diagnosed. CONCLUSIONS: 1) Surgical
      procedure is not indicated method of treatment of Wegener's granulomatosis,
      because it can increase the pathologic process. 2) The prognosis of Wegener's
      granulomatosis depends mainly on the ability to diagnose the early disease and
      the aplication of adequate treatment.

PMID- 16989449
TI  - [Assessment of the effectiveness of uvulopalatopharyngoplasty (UPPP) in the
      treatment of mild and moderate OSA patients preliminarily selected for the
      procedure by simple clinical examination].
AB  - INTRODUCTION: There is abundant conflicting information in the literature about
      prognostic value of sophisticated, diagnostic tests as well as data from simple
      clinical examination in its surgical treatment due to the complex nature of OSA.
      The aim of our study was to assess the efficacy of uvulopalatopharyngoplasty in
      the treatment of mild and moderate OSA patients who were preliminary selected by
      simple clinical examination. MATERIAL AND METHOD: 20 patients with obstructive
      sleep apnea syndrome were included in this study. There were patients who met the
      following criteria: RDI less than 30, BMI less than 30, collar size less than 43
      cm, normal nasal potency, modified Mallampati grade I or II, were enrolled in the
      study. The mean age of the patients was 45,5. Modified Mallampati score was used
      for evaluation the structures of oropharynx. RESULTS: 55% of patients were
      classified for grade I in Mallampati score and 45% of patients- grade II in this
      scale. At least 50% reduction of RDI after UPPP was observed in 75% of patients.
      The mean RDI was decreased from 21,35 in preoperative period to 9,85 in the
      control study. In 60% of our patients the RDI dropped to the value of less then
      10. In 5% of the patients, the surgical treatment did not decrease at least 50%
      of RDI. However in this patient group, we observed a slight improvement of mean
      minimal saturation (from 84,1 +/- 3,8 to 86,2% +/- 3,6). CONCLUSION: Using simple
      clinical parameters for preliminary selection of patients with mild and moderate
      OSA enabled us to achieve considerably better success rate after UPPP.

PMID- 16989450
TI  - [Objective assessment of the respiratory function of the larynx after fronto
      lateral laryngectomy with epiglottoplasty and after supracricoid laryngectomy
      with CHP or CHEP].
AB  - Enlarged fronto-lateral laryngectomy with epiglottoplasty and supracricoid
      laryngectomy with cricohyoidopexy (CHP) or cricohyoidoepiglottopexy (CHEP) differ
      from each other as regards surgical technique, extent of the resection and method
      of reconstruction. Despite of that, selected carcinomas of the true vocal cord
      staged as T2N0, which are included in indications to all mentioned
      laryngectomies, can be equally treated with each of these methods. The aim of
      this study is objective evaluation of the respiratory function of the larynx
      after three types of operation and comparison of the results. Material included
      64 patients treated during the period of 1993-2002: 39 patients after
      supracricoid laryngectomy (18 with CHP and 21 with CHEP) and 25 after enlarged
      fronto-lateral laryngectomy with epiglottoplasty. Spirometry was performed before
      and after the operation in 27 cases and only after the operation in 34 cases. The
      shapes of flow-volume loops and 32 spirometric parameters were evaluated. The
      decannulation rates were: a) 98,5% after enlarged fronto-lateral laryngectomy
      with epiglottoplasty, b) 80,6% after supracricoid laryngectomy with CHP, c) 70,1%
      after supracricoid laryngectomy with CHEP. Although the decannulation rate was
      better after CHP than after CHEP the spirometric parameters were better in
      patients after CHEP than in those after CHP. The airflow similar to normal was
      found in 15% patients after CHEP as well as after CHP and in 28% patients after
      epiglottoplasty. There were no restrictive abnormalities in the whole group of
      operated patients, but occurrences of obturation, especially inspiratory, were
      quite often. In conclusion, which follows from the comparison of three types of
      reconstructive laryngectomies, better results of respiratory function of the
      larynx were found after epiglottoplasty than after supracricoid laryngectomy with
      CHEP or CHP.

PMID- 16989451
TI  - [Analysis of results of stapedotomy in patients with obliterative otosclerosis].
AB  - INTRODUCTION: In obliterative type of otosclerosis the stapes footplate is
      greatly thickened and diffusely replaced by a massive otosclerotic masses that
      fill in the oval window niche, often annular ligament cannot be visualized. In
      the case of obliterative otosclerosis the only effective way of treatment is
      surgery. MATERIAL AND METHODS: The analysed group consisted of 53 patients with
      primary obliterative otosclerosis. In the control group there were 30 consecutive
      patients treated for otosclerosis. The auditory organ was assessed on the ground
      of the following criteria for the frequencies 0.5, 1, 2 and 4 kHz.: 1. Change of
      pure tone thresholds of air conduction (AC) 2. Change of pure tone thresholds of
      bone conduction (BC) 3. Change of pure tone thresholds of air-bone gap (ABG) as
      the difference between the mean AC and BC thresholds before the operation (AC0
      and BC0) and 12 months after the operation (AC1 and BC1). RESULTS:
      Postoperatively mean value of change of AC thresholds in the analysed group was
      about 24 +/- 2 dBHL and in the control group about 25 +/- 2 dBHL (no significant
      difference). In the analysed group the mean value of BC thresholds varied about 8
      dBHL and in the control group about 11 dBHL (no significant difference). The
      average values of ABG after the operation varied about 14 +/- 1 dBHL in both--the
      analysed and the control group. Postoperatively the mean value ABG was amounted
      to 20 +/- 1 dBHL in the analysed group and in the control group to 18 +/- 1 dBHL
      (no significant difference). On the basis of the subjective assessment completely
      subsidence of aural tinnitus reported 70% patients in the analysed group and 80%
      patients in the control group. CONCLUSION: 1. The incidence of obliterative
      otosclerosis represents 9,6% of all otosclerotic patients treated surgically. 2.
      Stapedotomy is the treatment of choice in patients with obliterative
      otosclerosis, because significant improvement of AC, BC and ABG 12 months after
      the operation was reported, mean values did not differ between the above and
      control group. 3. Complete subsidence of aural tinnitus was reported in 70%
      patients with obliterative otosclerosis.

PMID- 16989452
TI  - [Dychotomic tests in Polish for speech audiometry part 1: preparing material for
      the tests].
AB  - INTRODUCTION: Dychotomic tests in speech audiometry are extremely beneficial,
      especially in diagnosing central auditory processing disorders. MATERIALS AND
      METHODS: Basing on new articulatory lists (NLA-93), the authors have prepared a
      new set of language tests, including filtered speech test, numeral and verbal
      dichotic tests and Calearo test. CONCLUSIONS: The phonetic characteristics of the
      tests are presented, with special attention paid to their phonetic balance.

PMID- 16989453
TI  - [Subjective assessment of voice functions among teachers taking part in the
      rehabilitation program].
AB  - INTRODUCTION: In daily phoniatric practice, apart from laryngoscopy, another
      simple and useful method of examining the voice organ is perceptual voice
      assessment based on the GRBAS scale. An extension to this examination can be the
      Voice Handicap Index test (VHI). MATERIALS AND METHODS: 79 female teachers taking
      part in a 7-week-long rehabilitation course on voice emission techniques. Before
      and after the course the participants were subject to phoniatric examination
      including laryngovideostroboscopy, GRBAS scale assessment and determining the
      voice handicap index (VHI). RESULTS: After the course, a substantial improvement
      has been observed in voice emission, perceptual assessment and the VHI test. It
      has been observed that there is a statistically significant correlation between
      GRBAS and VHI results and mean phonation time (MPT) measured before and after the
      course. CONCLUSIONS: The VHI test should be included in complex analysis of the
      effects of intensive rehabilitation.

PMID- 16989455
TI  - [Influence of hyperbaric oxygen on the view of chicken's inner ear damage after
      exposure to wide-band noise].
AB  - The aim of the study was to assess the influence of hyperbaric oxygen on
      regeneration processes which take place in the inner ear (basilar papilla - BP)
      of chicken after exposure to wide-band noise at the level 120 dB for 48 hours. We
      found, that hyperbaric oxygen applied once a day after exposure to the noise
      restricted he extensiveness and decreased the dynamics of hair cells injury.
      Quantative and qualitive differences in histological changes which take place in
      chick basilar papilla after exposure to hyperbaric oxygen and glucocorticoids may
      prove the presence of different their effectory points of acting.

PMID- 16989454
TI  - [The local and sensual conditions of delay of voice breaking in adolescent boys].
AB  - Disorders of voice breaking in adolescent boys (mutational dysphonia) could be a
      result of local, hormonal, neuropsychiatric or sensual factors. The aim of this
      paper was the voice assessment of three subjects with incomplete mutation with
      particular additional factors, disturbing hearing, voice and speech: like hearing
      loss, hyperfunctional childhood dysphonia and speech dysfluency. Diagnostics
      included complete phoniatric examination with perceptive estimation,
      videostroboscopy and acoustic voice analysis, done before and after treatment.
      Rehabilitation process results were well seen in perceptive and objective voice
      analysis except significant improvement of fundamental frequency average.
      Analysis of incomplete mutation etiological factors need special attention due to
      coexist with another voice, speech and hearing disorders, which undergo with high
      tension of voice organ muscles or with the lack of phonation auditory feedback.

PMID- 16989456
TI  - [Head shaking test (HSN) using to diagnose vestibule damage].
AB  - INTRODUCTION: There is described a transient nystagmus provoked by shaking the
      head in the horizontal plane for a few seconds in both normal subjects and
      patients that is called Head Shaking Test (HSN) as a diagnostic tool for
      vestibular dysfunction. HSN is generally accepted that is generated by an
      asymmetrical peripheral vestibular input and a central velocity storage
      mechanism, which integrate and extend the peripheral vestibular signals. Purposes
      1. Creation of own modification method of stimulation and registration HSN 2.
      Estimation of HSN test value to show asymmetrical function of vestibular system
      3. Establish possibility of HSN test to localization of damage vestibular system
      4. Verification this test to use it as screening test MATERIAL AND METHODS:
      Studied group was consisted of 111 subjects that consist of 68 women and 43 men
      with mean age 52,4 years. All patients and controls were submitted to
      audiological tests and vestibular examinations According to the results of the
      otoneurological tests, patients were divided into: 36 with peripheral vestibular
      disease, 37 with central vestibular disease, 6 with both peripheral and central
      vestibular disease and 32 control persons. Own modified HSN test was described.
      Frequency of movements was approximately 2 Hz determined by metronome. HSN was
      recorded using ENG apparatus produced by Hartmann. RESULTS: In the first study
      stage incidence of HSN-H and HSN-V related to localization of vestibular organ
      damage, symmetric and asymmetric reaction in tested. It was observed more
      incidence of HSN-H and HSN-V in patients with peripheral and central lesion of
      vestibular system than in control group. Estimation of HSN incidence related to
      kinetic test--acceleration-deceleration rotary test shows the same HSN frequency
      in compared groups, with symmetric or asymmetric reaction in rotary test. HSN
      frequency related to caloric test (canal paresis) showed statistic differences
      between normal and canal paresis reaction in caloric test. Analysis incidence of
      HSN-V revealed no significant differences between examined groups. In the second
      studied stage the sensitivity and specificity were examined. CONCLUSIONS: 1. It
      is possible to make HSN test using metronome and ENG recording 2. HSN test may be
      use to reveal asymmetry of vestibular function. 3. HSN is helpful to diagnose
      peripheral and central lesion to some extent. 4. HSN is not useful as screening
      test

PMID- 16989458
TI  - [Analysis of usefulness of central auditory processes tests in children].
AB  - INTRODUCTION: Diagnostic of central auditory processing should be done in some
      group of children, especially with learning disabilities. MATERIAL AND METHODS:
      The audiological examination was performed in the group (n=24) of pupils from
      first class of secondary school (13-14 years) without any otological and
      neurological problems. The battery of audiological tests was used: pure tone,
      impedance and speech audiometry, two tests with low redundant speech: filtered
      speech (FS) and compressed sentences, sequencing tasks (FPT, DPT) and ABR. Normal
      answer: in FS - 80% correctly repeated words, FTP and DPT 75% correctly repeated
      sequences. RESULTS: Results of this examination were referred to the scores of
      test after primary school (max 40 points). Children were divided into 3 groups:
      group III (33-40 points), group II (21-32), group I (0-20). Because seven
      children havenit had stapedial reflex we put them into special group - NR group.
      Tympanometry and pure tone audiometry were normal in all children. Speech
      audiometry was performed in intensity 30dB and correct answers were repeated in
      80-100%. In compressed sentences test answers of 22 children were normal. The
      average dyscrimination score were: FS g. III 90%, g. II 84,3%, g. I 77,5%; FPT
      89,2%, 72,9%, 62,5%; DPT 82,5%, 71,4%, 62,5%. The percentage of normal answer
      were: FS g. III 100%, g. II 100%, g.I 75%, FPT 100%, 42,9%, 25%, DPT 66,7%,
      42,9%, 25%. The comparison between group I-III and NR was performed. The average
      dyscrimination score FS g. I-III 84,7%, g. NR 71,4%; FPT g. I-III 76,2%, g. NR
      72,1%; DPT g. I-III 73,5%, g. NR 50,7%. The percentage of normal answer were: FS
      g. I-III 94,1%, g. NR 42,9%; FPT g. I-III 58,8%, g. NR 28,6%, DPT g. I-III 47,1%,
      g. NR 28,6%. CONCLUSIONS: In central auditory tests (FS, FPT, DPT) worse results
      were in children without stapedial reflex. Good pupils (group III) had better
      results than poor ones (group I). The better results in audiological tests, the
      better scores in school test.

PMID- 16989457
TI  - [Otoacoustic emissions measurements in children during the chemotherapy because
      of the acute lymphoblastic leukemia].
AB  - INTRODUCTION: Chemotherapy is associated with an increased risk of ototoxic
      changes. The predictive value of conventional pure-tone audiometry on early
      detection of ototoxicity has been questioned. Otoacoustic emissions (OAEs) appear
      to be more sensitive to cochlear insult than the conventional pure-audiometry.
      The purpose of our study was (a) investigation the clinical usefulness of
      Distortion Product Otoacoustic Emissions (DPOAEs) as early indicator of
      chemotherapy-induced ototoxicity, (b) determination which of the protocols of
      chemotherapy is most ototoxic as measured by DPOAEs, (c) comparison of the short
      term and long-term effects of chemotherapy on DPOAEs. MATERIAL AND METHODS: Tonal
      audiometry (0,25-8 kHz), immitance audiometry and DPOAEs were measured in 10
      children with acute lymphoblastic leukemia (ALL). Measurements were performed
      before and after each protocol of ALL IC-BFM 2002 chemotherapy: protocol I:
      vincristine (VCR), L-asparaginase (L-ASP), daunorubicin (DNR), cyclophosphamide
      (CPM), cytarabine (ARA-C), 6-mercaptopurine (6-MP), methotrexate (MTX); protocol
      mM: 6-MP, MTX; protocol II: VCR, doxorubicin (DOX), L-ASP, CMP, ARA-C,
      thioguasine (6-TG), MTX; protocol III: VCR, DOX, L-ASP, CMP, ARA-C, 6-TG, MTX.
      DPOAEs were measured using ILO2 92 Otodynamics Analyser. Cochlear activity was
      evaluated by recording 2f1-f2 DPOAEs with L1 = 65 and L2 = 60 dB SPL. Comparisons
      of the DP-grams amplitudes were performed between baseline measurements and those
      recorded before and after each chemotherapy course. RESULTS: Our results indicate
      that: a)DPOAE is a more sensitive technique for the assess of chemotherapy
      induced ototoxicity than conventional audiometry, b) with DPOAE monitoring very
      subtle hearing changes can be detected, c) DPOAE amplitude was significantly
      decreased at all frequencies studied in 50% children with leukemia, d) depression
      of DPOAE amplitude was evident only during and after first protocol, e) long-term
      DPOAE monitoring reviled reversibility of ototoxicity in all children, f) a large
      individual variability in the DPOAE response following the chemotherapy was
      observed, g) in a few cases a transient increase in DPOAE amplitude had been
      observed before it was reduced. CONCLUSIONS: Distortion product otoacoustic
      emissions measurements are very sensitive on early detection of the changes in
      cochlear function and are recommended for monitor hearing in patients during
      chemotherapy.

PMID- 16989459
TI  - [Rare case of the Recklinghausen disease in the head and neck region].
AB  - INTRODUCTION: Neurofibromatosis type I (Recklinghausen disease) is one of the
      most common genetic disorders. Symptoms in head and neck region are present in
      nearly 30% of cases, but the most frequent are skin cafe-au-lait lesions or
      lesions localized in craniofacial region. Neurinomas of the last four cranial
      nerves are also described. MATERIAL AND METHODS: We discuss a case of a 50-year
      woman admitted to our department because of chronic pain symptoms localized in
      the head and neck region. A rare case of neurinoma of the X and XII nerves in the
      neck region was stated. This patient was successfully treated surgically with
      removing tumors, which involved vagal and hypoglossal nerve on the right side.
      CONCLUSIONS: The causal treatment is until now unknown and patients are carefully
      observed and scan with MRI. The possible treatment for patients are surgery when
      the lesion become painful or for cosmetic reasons. Also surgery with radiotherapy
      is require for tumors with malignant transformation which is possible in 5% of
      cases. The genetic guidance should be proposed to NF1 patients.

PMID- 16989460
TI  - [Pleomorphic adenoma of the palate. Case report].
AB  - Report on a huge pleomorphic adenoma (diameter 6 cm) of the right palate
      extending into the posterior part of the oral cavity. The dimension of the tumour
      and anatomical relations were documented with the use of nuclear magnetic
      resonance.

PMID- 16989462
TI  - [An unusual parotid gland foreign body].
AB  - A foreign body in the parotid gland is extremely uncommon. It can penetrate to
      the parotid gland through the skin or from the oral cavity via the Stenonis duct.
      A case of 23-years-old man with the several pieces of glass within the
      superficial lobe of the right parotid gland was described. The surgical removal
      was performed and the diagnosis of the foreign body was quite easy.

PMID- 16989461
TI  - [Olfactory neuroblastoma removed under endoscopic guidance].
AB  - INTRODUCTION: Olfactory neuroblastoma is a rare tumour associated with high rates
      of recurrence and mortality. Treatment includes surgery, radiotherapy,
      chemotherapy, or a combination. The ideal treatment modality has yet to be
      determined. MATERIAL AND METHODS: 46-years old male underwent bilateral
      endoscopic ethmoidectomy due to chronic sinusitis. During surgery, a 5 mm in
      diameter tumour was identified in the left superior nasal meatus. On
      histopathological examination the diagnosis of esthesioneuroblastoma was
      established and confirmed by immunohistochemistry. The tumour was classified
      according to Kadish as stage A, according to Biller as T1. MR scans performed two
      months later disclosed pathological tissues in the left ethmoid region. RESULTS:
      Multiple biopsies taken on subsequent frontosphenoethmoidectomy did not contain
      tumour cells. The patient declined radiotherapy. He has been asymptomatic over
      the 12 monthsi follow-up period. CONCLUSIONS: The exclusively surgical treatment
      proved effective due to early stage of the tumour and no evidence of infiltration
      of the frontal skull base. This strategy, however, requires frequent follow-up
      visits.

PMID- 16989463
TI  - [Facial palsy as the first syndrome of multiple sclerosis in 16 years old girl].
AB  - INTRODUCTION: Multiple sclerosis (MS) is demyelinating disease characterized by
      scattered neurologic deficits the central nervous system. The large number of
      scattered lessions produce many clinical symptoms. Facial palsy is rarely
      ascribed to multiple sclerosis as first syndrome. MATERIAL AND METHODS: 16-years
      old girl with sequence of features: 1. facial palsy, 2. transitional sudden
      hearing loss 3. transitory vertigo is presented. In audiologic examination pure
      tone audiogram, impedance audiometry, ABR and ENG were done. Air and bone
      thresholds were normal, stapedial reflex was absent and ABR suggested
      retrocochlear involvement in affected ear. RESULTS: In this case after MRI
      examination multiple sclerosis was diagnosed. CONCLUSION: ENT specialists should
      considered MS like a reason of facial palsy.

PMID- 16989464
TI  - [Tadeusz Antowski Ph.D. (1919-1966), from ENT Unit in Dachau to the lectureship
      in Otolaryngological Clinic of Poznan University].
AB  - The authors present the biography of the laryngologist Tadeusz Antowski Ph.D.
      (1919-1966). The medical studies at the University of Poznan, which he started
      with his brother Marian (1915-1943), were interrupted by World War II. During the
      Nazi occupation both students were imprisoned in the concentration camp in
      Dachau, where Marian died in a tragic accident. Tadeusz Antowski was appointed to
      work in the Laryngological-Eye Station in this camp. After the liberation of
      Poland he continued his study and work in Otolaryngological Clinic at Poznan
      University. Having done the PhD thesis he took over the lectureship in this
      clinic. Soon he was called up to the military service and in 1951 became the
      chief of Otolaryngological Department in the 8-th Army Hospital in Torun. He was
      an active member of Polish Medical Association and the president of the Torun
      branch. Tadeusz Antowski died on 02.11.1966 in Gdansk.

PMID- 16989465
TI  - [Distinction of sensorineural hearing loss by late response of acoustic evoked
      myogenic potentials (AWMP)].

PMID- 16989466
TI  - [Assessment of temporary threshold l shift after short-term impulse noise
      exposure].

PMID- 16989467
TI  - [Characteristics of non-infectious rhinitis in patients residing in a large city
      and in a small town].

PMID- 16989468
TI  - Let there be light.

PMID- 16989470
TI  - Uninformed consent.

PMID- 16989469
TI  - A better defense.

PMID- 16989471
TI  - Inpaint by numbers.

PMID- 16989472
TI  - Digestive decoys.

PMID- 16989473
TI  - Far-out physics.

PMID- 16989474
TI  - Contentious calculation.

PMID- 16989475
TI  - To serve man.

PMID- 16989477
TI  - Fiddling while the planet burns.

PMID- 16989476
TI  - Darwin on the right.

PMID- 16989478
TI  - The new age of wireless.

PMID- 16989479
TI  - How to blow up a star.

PMID- 16989480
TI  - Viral nano electronics.

PMID- 16989481
TI  - Peacekeepers of the immune system.

PMID- 16989483
TI  - Ballbots.

PMID- 16989482
TI  - Impact from the deep.

PMID- 16989484
TI  - Hydraulic engineering in prehistoric Mexico.

PMID- 16989486
TI  - Image stabilization. Steady cam.

PMID- 16989485
TI  - The promise of molecular imprinting.

PMID- 16989487
TI  - How do fast breeder reactions differ from regular nuclear power plant?

PMID- 16989489
TI  - Plasma and synovial fluid concentrations of nimesulide and its main metabolite
      after a single or repeated oral administration in patients with knee
      osteoarthritis.
AB  - The aim of this study was to evaluate plasma and synovial fluid concentrations of
      the non-steroidal anti-inflammatory drug nimesulide and its major metabolite
      (hydroxynimesulide, M1), after a single 100 mg dose of nimesulide and a repeated
      (14 day) administration, 100 mg twice a day, in patients with osteoarthritis of
      the knee and joint effusion. Nimesulide was rapidly absorbed in plasma and
      distributed in synovial fluid. On day 1, effective concentrations were present 30
      min after the first dose and on day 14, the synovial fluid concentration of
      nimesulide was significantly higher than that measured on day 1; no accumulation
      was observed in plasma. After 14 days of treatment, both the plasma and synovial
      fluid concentrations of M1 were significantly higher than those measured on day
      1. These data may help to explain the rapid onset of the analgesic effect of
      nimesulide demonstrated in several clinical conditions, including painful
      osteoarthritis.

PMID- 16989488
TI  - Cholinesterase inhibitors in the clinical management of Alzheimer's disease:
      importance of early and persistent treatment.
AB  - Alzheimer's disease is a neurodegenerative disease that greatly affects the
      quality of life of patients and their caregivers and places a heavy cost burden
      on the healthcare system. The cholinesterase inhibitors (ChEIs) donepezil,
      rivastigmine and galantamine have a central role in the treatment of Alzheimer's
      disease in the mild to moderate stages. Clinical trials with ChEIs have
      demonstrated therapeutic benefits for symptoms of cognition, function and
      behaviour across the disease course. These agents are most effective when started
      early in the disease course and used persistently, without treatment gaps. Early
      recognition of Alzheimer's disease and a global evaluation of treatment
      effectiveness are therefore essential. This article identifies barriers to early
      recognition and effective care of patients with Alzheimer's disease and discusses
      practical strategies to overcome them.

PMID- 16989490
TI  - Extract from Arca granosa L. inhibits proliferation of human tumour cell lines
      with kidney and lung origin.
AB  - Marine organisms are being considered increasingly as sources of anti-tumour
      agents. The extract from Arca granosa L. has been shown to decrease the growth of
      tumours and this study was undertaken to determine its ability and mechanism of
      inhibition. The extract inhibited the proliferation of six human tumour cell
      lines from different origins with varying sensitivity. The cell lines Ketr-3,
      A549 and NCl-H460 with kidney or lung origins were more sensitive to the extract
      than those of the HepG-2, MCF-7 and MGC-803 cells from other origins. In the
      three sensitive cell lines (Ketr-3, A549 and NCI-H460) the extract was shown to
      block different phases of the cell cycle progression and inhibit DNA synthesis in
      a concentration-dependent manner. It was concluded that the extract from A.
      granosa is potentially a novel anti-tumour agent, especially on kidney and lung
      tumour cell lines.

PMID- 16989491
TI  - Effect of underground working on vitamin D levels and bone mineral densities in
      coal miners: a controlled study.
AB  - The aim of this study was to determine the effect of underground working on 25
      hydroxyvitamin D (25-OHD) levels and bone mineral density (BMD) values in coal
      miners. Fifty coal miners working underground and 50 surface workers as controls,
      matched for age and body mass index, from Zonguldak, Turkey, were recruited to
      the study. Levels of 25-OHD, biochemical bone markers, and lumbar spine and femur
      BMD values were measured in all study participants. Lumbar spine and femur BMD
      values were significantly higher in underground workers compared with surface
      workers, but there was no significant difference in 25-OHD levels between the two
      groups. Duration of underground working, age, 25-OHD levels, cigarette
      consumption and dietary calcium intake were not correlated with BMD values.
      Underground physical working does not seem to be a significant risk factor for
      low 25-OHD levels or low BMD values.

PMID- 16989492
TI  - Direct detection of Bordetella pertussis and Bordetella parapertussis: comparison
      of polymerase chain reaction and culture.
AB  - We evaluated the diagnostic performance of a genomic DNA amplification method for
      Bordetella pertussis and Bordetella parapertussis compared with culture
      isolation. Aliquots from B. pertussis and B. parapertussis cultures were added to
      sterile physiological saline or sterile distilled water to give bacterial
      suspensions of 10(8) cells/ml and serial dilutions were prepared. Suspensions in
      physiological saline were cultured on charcoal agar medium; bacterial growth was
      observed up to dilutions of 10(-7). Suspensions in distilled water were subjected
      to DNA extraction and nested polymerase chain reaction (PCR) was performed on the
      extracts; the PCR was positive up to dilutions of 10(-8) for B. pertussis and 10(
      9) for B. parapertussis. Since the efficacy of culture isolation, regarded as the
      standard for the detection of B. pertussis and B. parapertussis, declines after
      the first stage of pertussis or with prior vaccination or antibiotic therapy,
      PCR, although not yet standardized, may provide an alternative diagnostic tool.

PMID- 16989493
TI  - Comparison of the effects of sevoflurane and propofol anaesthesia on regional
      cerebral glucose metabolism in humans using positron emission tomography.
AB  - This study compared brain glucose metabolism during sevoflurane anaesthesia and
      propofol anaesthesia using positron emission tomography (PET) in the same eight
      human volunteers. All the volunteers were anaesthetized twice, with a 1-week
      interval. Half of the volunteers received sevoflurane on the first occasion and
      propofol on the second; the other half received the two anaesthetics in the
      reverse order. PET scans using 18F-fluorodeoxyglucose were performed after
      sevoflurane or propofol anaesthesia. The relative glucose metabolic rate (rGMR)
      in the brain was assessed with statistical parametric mapping. Propofol
      suppressed the rGMR of the neocortex area more than sevoflurane, and sevoflurane
      suppressed the rGMR of the paleocortex and telencephalon more than propofol.
      These findings suggest that these two anaesthetics act via different mechanisms
      and may provide an important clue to the relationship between anaesthesia and the
      brain.

PMID- 16989494
TI  - Greater development of 1,2-dimethylhydrazine-induced colon cancer in a rat model
      of type 2 diabetes mellitus.
AB  - Several clinical cohort and case-control studies have suggested a link between
      diabetes and colon cancer. Otsuka Long-Evans Tokushima Fat (OLETF) rats
      spontaneously develop type 2 diabetes mellitus and Long-Evans Tokushima Otsuka
      (LETO) rats are non-diabetic. The relationship between type 2 diabetes mellitus
      and colon cancer was examined in these rats. The carcinogen 1,2-dimethylhydrazine
      was administered subcutaneously once weekly for 10 weeks, and the animals were
      killed and necropsied in week 29. All OLETF rats and 80% of the LETO rats
      developed cancer. The number of colon cancers per rat was significantly greater
      in the diabetic than in the non-diabetic rats. Although the tumours tended to be
      larger in diabetic rats, the difference was not statistically significant. No
      significant differences were observed in the depth of invasion or histological
      type of cancer in the two groups. Type 2 diabetes mellitus may enhance the
      generation and growth of colon cancer.

PMID- 16989495
TI  - Genomic copy-number aberrations related to lymph-node metastasis of colon cancer.
AB  - Lymph-node metastasis is an important indicator in the diagnosis of colon cancer.
      In order to determine the genes involved in metastasis, genomic copy-number
      aberrations in the primary tumours and lymph-node metastases were analysed in 12
      patients using comparative genomic hybridization. This method detects genomic
      copy-number changes at the chromosomal level and the identification of the
      regions of aberration on any chromosome. Copy-number gains at 6p12 and losses at
      8p12 were observed in a greater number of the primary tumours than in the
      metastases. These aberrations appear to be involved in lymph-node metastasis of
      colon cancer, and may allow measurement of the risk of lymph-node metastasis from
      a given colon cancer.

PMID- 16989496
TI  - Analysis of the relationship between sex and chromosomal aberrations in
      colorectal cancer by comparative genomic hybridization.
AB  - Colorectal cancer is thought to be more common in men than in women. The
      chromosomal locations of DNA gains and losses in surgical specimens of colorectal
      tumours were detected by comparative genomic hybridization and were compared by
      gender. Five chromosomal regions, 7p, 8p, 8q, Xp and Xq, contained multiple gains
      that were significantly more common in males than in females, and within these
      regions, the differences were significant for Xp21, Xp11.3, Xp11.4 and Xq26.
      Regions 1p, 3q, 11q, 12p, 12q and 15q contained multiple sites of gain that were
      significantly more common in females than in males. Tumours from male and female
      patients showed significantly more losses at 11p and 15q, and at 4q and Xq,
      respectively. The fact that gains in X-chromosomal regions were detected with a
      significantly higher frequency in tumours from male patients suggests that the
      difference between the genders might be explained by X-chromosomal inactivation.

PMID- 16989497
TI  - Comparative study of barnidipine and felodipine in Chinese patients with
      essential hypertension.
AB  - This study evaluated the efficacy and safety of barnidipine for the treatment of
      mild-to-moderate essential hypertension in Chinese patients. A total of 131
      patients were randomized to receive either barnidipine (10 -15 mg) or felodipine
      (5 - 10 mg) once daily for 4 weeks. Both drugs reduced blood pressure
      significantly, with > or = 87% of patients obtaining a marked or moderate effect.
      The mean +/- SD reductions in systolic and diastolic blood pressure were 19.2 +/-
      13.6 and 14.4 +/- 7.0 mmHg, respectively, for barnidipine treatment, and 20.3 +/-
      11.3 and 14.7 +/- 7.7 mmHg, respectively, for felodipine treatment. There were no
      significant differences between the two drugs in terms of anti-hypertensive
      effect, heart rate, laboratory test results or incidence of adverse events. More
      patients taking felodipine experienced palpitations, but this difference was not
      statistically significant. Barnidipine is as efficacious and safe as felodipine
      in the treatment of essential hypertension in Chinese patients.

PMID- 16989498
TI  - Plasma oxidants and antioxidants in acute ischaemic stroke.
AB  - Plasma levels of the oxidants xanthine oxidase, nitric oxide and malondialdehyde
      and the antioxidants superoxide dismutase, glutathione peroxidase and glutathione
      reductase, together with total superoxide scavenger activity and non-enzymatic
      superoxide scavenger activity, were determined in 19 patients with acute
      ischaemic stroke and 20 controls. Compared with controls, superoxide dismutase,
      total superoxide scavenger activity, glutathione peroxidase and glutathione
      reductase activities were significantly lower, and nitric oxide and
      malondialdehyde levels significantly higher, in acute stroke patients. Xanthine
      oxidase showed a slight but non-significant increase in stroke patients compared
      with controls. There was no significant difference in non-enzymatic superoxide
      scavenger activity between the two groups. There was a positive correlation
      between glutathione reductase levels and Glasgow Coma Scale scores, and a
      negative correlation between malondialdehyde levels and non-enzymatic superoxide
      scavenger activity. These findings suggest that oxidative stress in patients with
      acute ischaemic stroke may be the result of an imbalance in oxidant/antioxidant
      homeostasis.

PMID- 16989499
TI  - Impaired blood rheology in critically ill patients in an intensive care unit.
AB  - Critically ill patients are at increased risk of thromboembolic complications.
      Japanese patients admitted to the intensive care unit of Gunma University
      Hospital were divided into critically ill (high score) and moderately ill (low
      score) groups according to mean Acute Physiology and Chronic Health Evaluation
      (APACHE) II score. White blood cell count, potassium, creatinine, immunoglobulin
      G and blood passage time, measured using the microchannel method, were
      significantly higher and the platelet aggregation score and platelet count were
      significantly lower in the high-score group than in the low-score group, but
      other haemorheological parameters did not differ significantly between the two
      groups. White blood cell count, potassium, creatinine, APACHE II score and levels
      of immunoglobulins G, A and M were positively correlated with blood passage time
      in all patients. Critically ill patients had impaired blood rheology, which could
      result from increased white blood cell count, potassium, creatinine and
      immunoglobulins and may be associated with the pathophysiology of the
      thromboembolic process.

PMID- 16989500
TI  - Unilateral anterior uveitis in Melkersson-Rosenthal syndrome: a case report.
AB  - Melkersson-Rosenthal syndrome (MRS) is an uncommon granulomatous condition
      characterized by persistent or recurrent orofacial oedema, relapsing facial
      paralysis and fissured tongue. We report here a case of MRS with the classical
      triad of signs accompanied by unilateral anterior uveitis. A 35-year-old man with
      a fissured tongue, recurrent facial palsy and orofacial oedema presented with a 3
      month history of conjunctival redness and decreased vision in the right eye. On
      evaluation of visual acuity, the patient was only able to count fingers. Slit
      lamp examination revealed severe conjunctival injection, cells and flare,
      posterior synechiae and keratic precipitates. Examination of the left eye
      revealed no evidence of inflammation. Examination of the other systems was
      normal. The patient was treated with topical corticosteroids and cycloplegics and
      the visual acuity improved to 7/10. To our knowledge, there are no previous
      reports of an association between uveitis and MRS.

PMID- 16989501
TI  - Cardiac arrest due to a vagal reflex potentiated by thoracic epidural analgesia.
AB  - Reflex bradycardia and cardiac arrest may be the result of a vagal reflex, which
      can occur during a variety of surgical procedures. We report a patient who
      developed cardiac arrest as a result of a vagal reflex that was potentiated by
      thoracic epidural analgesia during general anaesthesia. A 53-year-old man was
      scheduled for subtotal gastrectomy because of an early gastric adenocarcinoma.
      After an epidural catheter had been inserted, general anaesthesia was induced.
      During surgery, an abdominal self-retaining retractor was set up but bradycardia
      and cardiac arrest developed. The patient returned to a normal sinus rhythm after
      successful resuscitation. We conclude that bradycardia as a result of a vagal
      reflex is mediated by potent abdominal wall traction and is potentiated by
      epidural analgesia. Early diagnosis and proper treatment can allow a full
      recovery, even in high-risk patients.

PMID- 16989502
TI  - Advanced oesophageal carcinoma in an 84-year-old treated with chemoradiotherapy.
AB  - We present a case of advanced oesophageal cancer with cardiac invasion in an 84
      year-old male presenting with dysphagia and general malaise. Histological
      analysis of an endoscopic biopsy specimen revealed a poorly differentiated
      squamous cell carcinoma. Computed tomography indicated a thickened oesophageal
      wall that was compressing the left atrium, suggesting invasion of the heart, and
      oesophagography revealed a polypoid lesion 9 cm in length. No distant metastases
      were seen on computed tomography. The patient was given chemotherapy with 10
      mg/m2 cisplatin on days 1 and 4 every week for 5 weeks and concurrent
      radiotherapy at a dose of 2 Gy five times per week (total dose 52 Gy). After 4
      weeks, the mass was no longer visible on oesophagography or endoscopic
      examination. The patient was free of recurrence and metastases for 4.5 years. In
      conclusion, chemoradiotherapy may be curative in elderly patients with
      unresectable oesophageal carcinoma.

PMID- 16989504
TI  - The spread of alien species is considered to be one of the greatest threats to
      biological diversity.

PMID- 16989503
TI  - Cytokeratin expression in subungual squamous cell carcinoma.
AB  - Cytokeratin expression in subungual squamous cell carcinoma was investigated in
      order to evaluate the origin and state of differentiation of the tumour. The
      tumour nests contained cytokeratin 14, 16 and 17, which were also expressed in
      the nail bed. Therefore, cytokeratin expression in subungual squamous cell
      carcinoma may reflect its indolent clinical prognosis.

PMID- 16989505
TI  - Spatial characterization of the Baltic sea drainage basin and its unmonitored
      catchments.
AB  - We present an updated, harmonized hydrologic base map of the entire Baltic Sea
      Drainage Basin (BSDB), including 634 subdrainage basins. The updated map has a
      level of detail approximately 5 to 10 times higher than the current standard and
      includes various spatial-aggregation possibilities of relevance for water
      management. All 634 subdrainage basins and their various spatial aggregations are
      characterized in terms of population, land cover, drainage density, and slope. We
      identify, quantify, and characterize, in particular, drainage basins that are
      unmonitored with regard to the combination of water-flow and nutrient
      concentration measurements needed to monitor coastal nutrient and pollutant
      loading. Results indicate that out of a total BSDB population of 84 239 000 in
      2002, 24% lived in unmonitored coastal drainage basins that cover 13% of the
      total BSDB area. A more detailed analysis of Swedish catchments indicates that
      Sweden has a particularly large proportion of unmonitored coastal catchment areas
      (20% of the total Swedish area) with high population pressures (55% of the total
      Swedish population), when compared with average conditions for the whole BSDB. In
      general, the investigated characteristics of unmonitored coastal basins vary and
      differ largely from those in adjacent monitored drainage basins within the BSDB.

PMID- 16989506
TI  - Perceived and measured levels of environmental pollution: interdisciplinary
      research in the subarctic lowlands of northeast European Russia.
AB  - Using interdisciplinary field research in the Usa Basin, northeast European
      Russia, we compared local inhabitants' perception of environmental problems with
      chemical and remote-sensing signatures of environmental pollution and their local
      impacts. Extensive coal mining since the 1930s around Inta and Vorkuta has left a
      legacy of pollution, detected by measuring snowpack, topsoil, and lichen
      chemistry, together with remote-sensing techniques and analysis of lake water and
      sediments. Vorkuta and its environs suffered the worst impacts, with significant
      metal loading and alkalization in lakes and topsoils, elevated metals and cations
      in terricolous (reindeer) lichens, and changes in vegetation communities.
      Although the coal industry has declined recently, the area boasts a booming oil
      and gas industry, based around Usinsk. Local perceptions and concerns of
      environmental pollution and protection were higher in Usinsk, as a result of
      increased awareness after a major oil spill in 1994, compared with Vorkuta's
      inhabitants, who perceived air pollution as the primary environmental threat. Our
      studies indicate that the principal sources of atmospheric emissions and local
      deposition within 25 to 40 km of Vorkuta were coal combustion from power and
      heating plants, coal mines, and a cement factory. Local people evaluated air
      pollution from direct observations and personal experiences, such as
      discoloration of snow and respiratory problems, whereas scientific knowledge
      played a minor role in shaping these perceptions.

PMID- 16989507
TI  - Trends in nitrate concentrations and determination of its origin using stable
      isotopes (18O and 15N) in groundwater of the Western Central Valley, Costa Rica.
AB  - A study was conducted to evaluate long-term trends in nitrate concentrations and
      to try to identify the origin of nitrate using stable isotopes (15N(NO3-) and
      18O(NO3-)) in the aquifers of the western Central Valley, Costa Rica, where more
      than 1 million people depend on groundwater to satisfy their daily needs. Data
      from 20 sites periodically sampled for 4 to 17 years indicate an increasing trend
      in nitrate concentrations at five sites, which in a period ranging from 10 to 40
      years, will exceed recommended maximum concentrations. Results of isotopic
      analysis indicate a correspondence between land use patterns and the isotopic
      signature of nitrate in groundwater and suggest that urbanization processes
      without adequate waste disposal systems, followed by coffee fertilization
      practices, are threatening water quality in the region. We conclude that
      groundwater management in this area is not sustainable, and that land use
      substitution processes from agricultural activity to residential occupation that
      do not have proper sewage disposal systems may cause a significant increment in
      the nitrate contaminant load.

PMID- 16989508
TI  - Incorporating green-area user groups in urban ecosystem management.
AB  - We analyze the role of urban green areas managed by local user groups in their
      potential for supporting biodiversity and ecosystem services in growing city
      regions, with focus on allotment areas, domestic gardens, and golf courses. Using
      Stockholm, Sweden, as an example cityregion, we compile GIS data of its spatial
      characteristics and relate these data to GIS data for protected areas and "green
      wedges" prioritized in biodiversity conservation. Results reveal that the three
      land uses cover 18% of the studied land area of metropolitan Stockholm, which
      corresponds to more than twice the land set aside as protected areas. We review
      the literature to identify ecosystem functions and services provided by the three
      green areas and discuss their potential in urban ecosystem management. We
      conclude that the incorporation of locally managed lands, and their stewards and
      institutions, into comanagement designs holds potential for improving conditions
      for urban biodiversity, reducing transaction costs in ecosystem management, and
      realizing local Agenda 21.

PMID- 16989509
TI  - No-take marine reserves and reef fisheries management in the Philippines: a new
      people power revolution.
AB  - The marine-conservation and reef fisheries-management program that exists today
      in the Philippines had humble beginnings in the 1970s at Sumilon and Apo islands.
      These islands have produced some of the best evidence available that no-take
      reserves, protected and managed by local communities, can play a key role in
      biodiversity conservation and fisheries management. Perhaps more importantly,
      they served as models for an extraordinary expansion of no-take reserves
      nationally in the Philippines in the past 2 decades. This expansion contributed
      substantially to a major shift in national policy of management of marine
      resources. This policy shift partially devolved responsibility from a centralized
      government bureaucracy to local governments and local communities. Local
      governments now comanage, along with the national government, marine resources
      out to 15 km from the coast. Giving some responsibility for management of marine
      resources to coastal people dependent upon those resources represents, in a very
      real sense, another "people power revolution" in the Philippines.

PMID- 16989510
TI  - Release of alien populations in Sweden.
AB  - Introduction of alien species is a major threat to biological diversity. Although
      public attention typically focuses on the species level, guidelines from the
      Convention of Biological Diversity define alien species to include entities below
      species level. This inclusion recognizes that release of nonlocal populations of
      native species may also result in negative effects on biodiversity. In practice,
      little is known about the extent, degree of establishment, or the effects on
      natural gene pools of such releases. Existing information on the releases in
      Sweden shows that alien populations are spread to a great extent. The most
      commonly released species include brown trout, Atlantic salmon, Arctic char,
      common whitefish, Scots pine, Norway spruce, mallard duck, gray partridge, and
      pheasant. Although millions of forest trees, fish, and birds are released
      annually, poor documentation makes the geographic and genetic origin of these
      populations, as well as the sites where they have been released, largely unclear.
      We provide recommendations for urgently needed first steps relating to the risks
      and problems associated with release of alien populations.

PMID- 16989511
TI  - Toward a sustainable experience in an intermountain valley in northwestern
      Argentina.

PMID- 16989512
TI  - Indigenous use and trade of dugong (Dugong dugon) in Sabah, Malaysia.

PMID- 16989513
TI  - Restoration and management of the Inner Mongolia grassland require a sustainable
      strategy.

PMID- 16989514
TI  - The headwater loss of the western plateau exacerbates China's long thirst.

PMID- 16989515
TI  - A fructan, from Radix ophiopogonis, stimulates the proliferation of cultured
      lymphocytes: structural and functional analyses.
AB  - A fructan, Opaw-2, with molecular mass of about 14 kDa, was isolated from the
      tuberous roots of Ophiopogon japonicus. Opaw-2 comprises fructose and glucose
      with a molar ratio of 30:1. Linkage and NMR analyses indicated that Opaw-2 has a
      backbone structure of beta-(1-->2)-Fruf and beta-(2-->6)-Fruf residues that
      branches at O-6 of beta-(1-->2)-Fruf residues with alpha-1-linkage to the Glcp
      residues and terminates with Fruf residues. In cultured lymphocytes, the
      application of Opaw-2 significantly stimulated the proliferation of lymphocytes
      in a dose-dependent manner. By using atomic force microscopy, Opaw-2 showed a
      morphological change from globular to helical fibrous shape at increasing
      concentrations.

PMID- 16989516
TI  - Minor sesquiterpenes with new carbon skeletons from the brown alga Dictyopteris
      divaricata.
AB  - Five minor sesquiterpenes (1-5) with two novel carbon skeletons, together with a
      minor new oplopane sesquiterpene (6), have been isolated from the brown alga
      Dictyopteris divaricata. By means of spectroscopic data including IR, HRMS, 1D
      and 2D NMR, and CD, their structures including absolute configurations were
      assigned as (+)-(1R,5S,6S,9R)-3-acetyl-1-hydroxy-6-isopropyl-9
      methylbicyclo[4.3.0]non-3-ene (1), (+)-(1R,3S,4S,5R,6S,9R)-3-acetyl-1,4-dihydroxy
      6-isopropyl-9-methylbicyclo[4.3.0]nonane (2), (+)-(1R,3R,4R,5R,6S,9R)-3-acetyl
      1,4-dihydroxy-6-isopropyl-9-methylbicyclo[4.3.0]nonane (3), (+)-(1S,2R,6S,9R)-1
      hydroxy-2-(1-hydroxyethyl)-6-isopropyl-9-methylbicyclo[4.3.0]non-4-en-3-one (4),
      (-)-(5S,6R,9S)-2-acetyl-5-hydroxy-6-isopropyl-9-methylbicyclo[4.3.0]non-1-en-3
      one (5), and (-)-(1S,6S,9R)-4-acetyl-1-hydroxy-6-isopropyl-9
      methylbicyclo[4.3.0]non-4-en-3-one (6). Biogenetically, the carbon skeletons of 1
      6 may be derived from the co-occurring cadinane skeleton by different ring
      contraction rearrangements. Compounds 1-6 were inactive (IC(50) > 10 mug/mL)
      against several human cancer cell lines.

PMID- 16989517
TI  - Russujaponols A-F, illudoid sesquiterpenes from the fruiting body of Russula
      japonica.
AB  - Six new illudoid sesquiterpenes, russujaponols A-F (1-6), were isolated from the
      fruiting bodies of Russula japonica Hongo. Their structures were established
      primarily by 2D NMR experiments, and the structure of the main compound,
      russujaponol A (1), was confirmed by X-ray crystallographic analysis of its
      benzoate (1a). Russujaponol A (1) suppressed invasion of human fibrosarcoma
      (HT1080) cells into Matrigel in a concentration-dependent manner and caused 63%
      inhibition at 3.73 microM.

PMID- 16989518
TI  - Tripfordines A-C, sesquiterpene pyridine alkaloids from Tripterygium wilfordii,
      and structure anti-HIV activity relationships of Tripterygium alkaloids.
AB  - Three new sesquiterpene pyridine alkaloids, tripfordines A-C (1-3), were isolated
      from an ethanolic extract of the roots of Tripterygium wilfordii, along with
      eight known pyridine alkaloids, and tested for in vitro cytotoxic and anti-HIV
      activity. The structures of the new compounds were established on the basis of
      spectroscopic data interpretation. Anti-HIV structure-activity relationships
      (SAR) for this compound type are proposed on the basis of the screening results
      from the newly isolated compounds and prior data of known sesquiterpene pyridine
      alkaloids. The position of a carboxyalkyl chain on the pyridine moiety was not
      critical since both 2'- and 4'-substituted compounds exhibited high anti-HIV
      activity (EC(50) 0.1 microg/mL). In contrast, a hydroxy group at C-8'
      (carboxypropyl side chain) or C-9' (carboxybutyl side chain) was found to affect
      anti-HIV activity.

PMID- 16989519
TI  - Polyoxygenated sterols from the Formosan soft coral Sinularia gibberosa.
AB  - Chemical investigation on the dichloromethane-soluble fraction from the EtOH
      extract of Sinularia gibberosa Tixier-Durivault has led to the isolation of three
      new polyoxygenated sterols, gibberoketosterols B (1) and C (2) and
      gibberoepoxysterol (3), along with two known steroids, gibberoketosterol (4) and
      24-methylenecholest-5-en-3beta-ol (5). These cholestane-type sterols possessing a
      22,24(28)-conjugated diene (1 and 2) in the side chain or a 5alpha,6alpha-epoxide
      in the B-ring (3) were isolated for the first time from marine sources. Compound
      4 showed significant inhibition against the up-regulation of the pro-inflammatory
      iNOS and COX-2 proteins of LPS-stimulated RAW264.7 macrophage cells, while 1 was
      found to be inactive. The cytotoxicity of 1-4 toward a limited panel of cancer
      cell lines is also reported.

PMID- 16989520
TI  - Identification of major and minor constituents of Harpagophytum procumbens
      (Devil's claw) using HPLC-SPE-NMR and HPLC-ESIMS/APCIMS.
AB  - The HPLC-SPE-NMR technique, supported by HPLC-MS measurements, was used to
      determine structures of major as well as some minor constituents of ethanol and
      petroleum ether extracts of Harpagophytum procumbens (Devil's claw) roots. This
      method was also shown to be applicable for rapid and precise on-line
      identification of secondary metabolites present in commercial herbal products of
      H. procumbens. A total of 15 compounds (1-14 and 17) were identified from the
      ethanol and petroleum ether extracts, including a novel Diels-Alder dimer 14.
      Optimization of the HPLC-SPE-NMR experiments included quantitative (1)H NMR
      measurements, determination of trapping and elution efficiency, effect of
      multiple trapping of analytes, use of various deuterated solvents for SPE
      cartridge elution, and effect of post-column dilution ratio of eluent with water.
      Linear accumulation of apolar and relatively polar analytes was demonstrated for
      at least 8-10 repeated trappings, resulting in greatly improved signal-to-noise
      ratios in NMR spectra and reduced acquisition times. Thus, the HPLC-SPE-NMR
      technique provides an efficient means of identification of multiple components of
      crude extracts. By allowing on-line generation of high-quality 2D NMR data
      without traditional purification of extract components, the HPLC-SPE-NMR
      methodology represents a paradigm shift in natural products research with respect
      to structure elucidation.

PMID- 16989521
TI  - Cytotoxic monotetrahydrofuran acetogenins from Disepalum plagioneurum.
AB  - The known plagionicin A (1) and eight new monotetrahydrofuran acetogenins,
      plagionicins B-D (2-4) and plagioneurins A-E (5-9), were isolated from the leaves
      of Disepalum plagioneurum by bioassay-guided purification. The structures of the
      new compounds were elucidated by spectroscopic methods. The new
      monotetrahydrofuran (mono-THF) acetogenins exhibited significant in vitro
      cytotoxicity against the KB cancer cell line, with IC(50) values in the nanomolar
      range.

PMID- 16989522
TI  - Grandisines C-G, indolizidine alkaloids from the Australian rainforest tree
      Elaeocarpus grandis.
AB  - Five new indolizidine alkaloids, grandisines C, D, E, F, and G (4-8), and one
      known indolizidine alkaloid, (-)-isoelaeocarpiline (3), were isolated from the
      leaves of Elaeocarpus grandis and their structures determined by 1D and 2D NMR
      spectroscopy. Grandisine C (4) is isomeric with the known compound rudrakine (1).
      The absolute configuration of grandisine D (5) was deduced by its conversion to (
      )-isoelaeocarpiline. Grandisine E (6) contains a novel tetracyclic ring system.
      Grandisine F (7) is the 14-amino analogue of grandisine C. Grandisine G (8)
      contains the novel combination of a piperidine attached to an indolizidine.
      Grandisines C, D, F, and G and (-)-isoelaeocarpiline showed receptor binding
      affinity for the human delta-opioid receptor with IC(50) values of 14.6, 1.65,
      1.55, 75.4, and 9.9 microM, respectively.

PMID- 16989523
TI  - Dovyalicin-type spermidine alkaloids from Dovyalis species.
AB  - Phytochemical investigations of Dovyalis abyssinica, D. hebecarpa, and D.
      macrocalyx revealed two new spermidine-type alkaloids, dovyalicin E (3) and
      dovyalicin F (4), along with the previously described dovyalicin A (1),
      dovyalicin B (2), and dovyalicin C (5). In addition, a new phenol glucoside, 4
      hydroxytremulacin (7), and the new 1,2-cyclohexanediol glucoside 9, as well as
      the known compounds methyl 1-hydroxy-6-oxocyclohex-2-enecarboxylate (6) and
      tremulacin (8), were isolated. The structures were established using homo- and
      heteronuclear two-dimensional NMR experiments and chiroptical methods. At ambient
      temperature, the N-disubstituted amide 4 exists as a mixture of cis and trans
      conformers. Variable-temperature (1)H NMR studies showed that time-averaged
      spectra are obtainable at 348 K, and the activation parameters determined for the
      rotation about the amide bond were DeltaH++ = 89 +/- 4.6 kJ/mol, DeltaS++ = 65 +/
      14 kJ/mol.K, and DeltaG++(298K) = 70 +/- 4.5 kJ/mol.

PMID- 16989524
TI  - Antidepressant principles of the roots of Polygala tenuifolia.
AB  - [(125)I]RTI-55-membrane binding assay-guided fractionation and separation of a
      water-soluble extract of the roots of Polygala tenuifolia gave five new
      oligosaccharide derivatives, polygalatenosides A-E (1-5). The structures of these
      new oligosaccharides were established on the basis of spectroscopic evidence.
      Polygalatenosides A and B (1 and 2) showed significant inhibitory activity, with
      IC(50) values of 30.0 and 6.04 microM, respectively, in this membrane binding
      assay and acted as norepinephrine reuptake inhibitors through blocking
      norepinephrine transport.

PMID- 16989525
TI  - Hydroxylated gedunin derivatives from Cedrela sinensis.
AB  - Four new limonoids, 11alpha-hydroxygedunin (1), 11beta-hydroxygedunin (2), 7
      deacetoxy-7alpha,11alpha-dihydroxygedunin (3), and 7-deacetoxy-7alpha,11beta
      dihydroxygedunin (4), were isolated from the cortex of Cedrela sinensis, together
      with three known compounds, gedunin (5), 7-deacetoxy-7alpha-hydroxygedunin (6),
      and 11-oxogedunin (7). The structures of 1-4 were determined by a combination of
      2D NMR experiments and chemical methods and by X-ray crystallography of 1 and 2.

PMID- 16989526
TI  - Tirucallane, apotirucallane, and octanorapotirucallane triterpenes of Simarouba
      amara.
AB  - A chemical investigation of the bark of Simarouba amara, collected in Barbados,
      resulted in the isolation of six new triterpenes (3-8), in addition to two known
      compounds, 3-oxatirucalla-7, 24-dien-23-ol (1) and niloticin (2). Compound 3 is a
      tirucallane triterpene, while compounds 4-7 are apotirucallane derivatives
      containing an epsilon-lactone in ring A. Compounds 6 and 7 were obtained as a
      mixture that could not be separated, while compound 8 is an octanorapotirucallane
      derivative that lacks the C(8) side chain. The structures of all compounds were
      determined by interpretation of physical data.

PMID- 16989528
TI  - Antiproliferative triterpene saponins from Entada africana.
AB  - Nine new ester saponins (1-9) were isolated from the roots of Entada africana.
      Their structures were elucidated by 1D and 2D NMR experiments including 1D and 2D
      TOCSY, DQF-COSY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis, and
      chemical methods. The aglycon moieties were found to be echinocystic acid for
      compounds 1, 2, 4-6, 8, and 9 and acacic acid for 3 and 7. All isolated compounds
      were tested for their antiproliferative activity against the J774.A1, HEK-293,
      and WEHI-164 cell lines. Moderate to high cytotoxic potency was found for almost
      all compounds tested.

PMID- 16989527
TI  - Cardenolide glycosides from Pergularia tomentosa and their proapoptotic activity
      in Kaposi's sarcoma cells.
AB  - Continuing our investigations on plants belonging to the Asclepiadaceae family,
      three new cardenolide glycosides, 3'-O-beta-D-glucopyranosylcalactin (1), 12
      dehydroxyghalakinoside (2), and 6'-dehydroxyghalakinoside (3), along with the
      known ghalakinoside (4) and calactin (5), were isolated from the roots of
      Pergularia tomentosa. The structures of these compounds were elucidated by
      extensive spectroscopic methods including 1D- and 2D-NMR experiments as well as
      ESIMS analysis. The isolated cardenolides caused apoptotic cell death of Kaposi's
      sarcoma cells.

PMID- 16989529
TI  - Oculatol, oculatolide, and A-nor sterols from the sponge Haliclona oculata.
AB  - Chemical investigation of the marine sponge Haliclona oculata resulted in the
      isolation of eight new compounds including oculatol (1) and oculatolide (2) and
      six unusual A-nor steroids, 2-ethoxycarbonyl-2beta-hydroxy-A-nor-ergosta-5,24(28)
      dien-4-one (3), 2-ethoxycarbonyl-24-ethyl-2beta-hydroxy-A-nor-cholesta-5-en-4-one
      (4), 2-ethoxycarbonyl-2beta,7beta-dihydroxy-A-nor-ergosta-5,24(28)-dien-4-one
      (5), 2-ethoxycarbonyl-2beta,7beta-dihydroxy-A-nor-cholesta-5-en-4-one (6), 2
      ethoxycarbonyl-2beta,7beta-dihydroxy-24-methyl-A-nor-cholesta-5,22(E)-dien-4-one
      (7), and 2-ethoxycarbonyl-2beta,7beta-dihydroxy-A-nor-cholesta-5,22(E)-dien-4-one
      (8), along with 16 known steroids and indole derivatives. Their structures were
      unambiguously determined on the basis of extensive spectroscopic analyses.

PMID- 16989530
TI  - Absolute configuration of natural diastereoisomers of 6beta-hydroxyhyoscyamine by
      vibrational circular dichroism.
AB  - The absolute configuration of the two natural diastereoisomers of 6beta
      hydroxyhyoscyamine has been determined using vibrational circular dichroism (VCD)
      spectroscopy. The predicted VCD and IR spectra of (3R,6R,2'S)-6beta
      hydroxyhyoscyamine (1) and (3S,6S,2'S)-6beta-hydroxyhyoscyamine (2) were
      calculated using density functional theory (DFT) with the B3LYP functional and 6
      31G(d) basis set and considering the eight lower energy conformations of each
      diastereoisomer. In both cases, the first four conformers showed the N-Me group
      in the syn orientation, permitting the formation of a hydrogen bond between the
      hydroxy group at the tropane ring and the tertiary nitrogen atom. In addition the
      eight conformers showed an intramolecular hydrogen bond between the hydroxy and
      carbonyl groups of the tropic ester moiety. The calculated IR spectra of both
      molecules showed good agreement with the experimental spectra, while comparison
      of the experimental and calculated VCD spectra showed that the absolute
      configuration of dextrorotatory 6beta-hydroxyhyoscyamine is (3R,6R,2'S), while
      the levorotatory isomer is (3S,6S,2'S).

PMID- 16989531
TI  - Taspine: bioactivity-guided isolation and molecular ligand-target insight of a
      potent acetylcholinesterase inhibitor from Magnolia x soulangiana.
AB  - A bioactivity-guided approach was taken to identify the acetylcholinesterase
      (AChE, EC 3.1.1.7) inhibitory agent in a Magnolia x soulangiana extract using a
      microplate enzyme assay with Ellman's reagent. This permitted the isolation of
      the alkaloids taspine (1) and (-)-asimilobine (2), which were detected for the
      first time in this species. Compound 1 showed a significantly higher effect on
      AChE than the positive control galanthamine and selectively inhibited the enzyme
      in a long-lasting and concentration-dependent fashion with an IC(50) value of
      0.33 +/- 0.07 muM. Extensive molecular docking studies were performed with human
      and Torpedo californica-AChE employing Gold software to rationalize the binding
      interaction. The results suggested ligand 1 to bind in an alternative binding
      orientation when compared to galanthamine. While this is located in close
      vicinity to the catalytic amino acid triad, the 1-AChE complex was found to be
      stabilized by (i) sandwich-like pi-stacking interactions between the planar
      aromatic ligand (1) and the Trp84 and Phe330 of the enzyme, (ii) an esteratic
      site anchoring with the amino side chain, and (iii) a hydrogen-bonding network.

PMID- 16989532
TI  - Alkaloids from Gelsemium elegans.
AB  - Three new alkaloids, gelsebanine (1), 14alpha-hydroxyelegansamine (2), and
      14alpha-hydroxygelsamydine (3), and a new extraction artifact , gelsebamine (4),
      together with 12 known alkaloids, were isolated from the stems and leaves of
      Gelsemium elegans. The structures of 1-4 were determined by spectroscopic
      methods, especially 2D NMR techniques. Compounds 1-4 were evaluated for cytotoxic
      activity against four tumor cell lines, and gelsebamine (4) selectively inhibited
      the A-549 human lung adenocarcinoma cell line.

PMID- 16989533
TI  - Cyclopentenones, scaffolds for organic syntheses produced by the endophytic
      fungus mitosporic dothideomycete sp. LRUB20.
AB  - Two new natural products, 2-hydroxymethyl-3-methylcyclopent-2-enone (1)
      (synthetically known) and cis-2-hydroxymethyl-3-methylcyclopentanone (2), and a
      known compound, asterric acid (3), were isolated from the endophytic fungus
      mitosporic Dothideomycete sp. LRUB20, which was isolated from the stem of the
      Thai medicinal plant Leea rubra. Compound 2 was separated and identified in the
      form of its 2,4-dinitrophenylhydrazone derivative (5). Compounds 1, 3, and
      hydrazone 5 exhibited mild antimycobacterial activity, both with MIC values of
      200 microg/mL. Compounds 1, 3, and 4 were inactive (at 50 microg/mL) toward Vero,
      KB, NCI-H187, and BC cell lines. Hydrazone 5 showed only mild cytotoxicity
      against the Vero cell line with an IC(50) value of 21.7 microg/mL; however, it
      was inactive toward KB, NCI-H187, and BC cell lines. Endophytic fungi may be a
      source for the production of building blocks for organic syntheses.

PMID- 16989534
TI  - Humulane-type sesquiterpenoids from the mushroom Lactarius mitissimus.
AB  - Five new humulane-type sesquiterpenes, mitissimols A (1), B (2), and C (3), and a
      mixture of mitissimol A oleate (4) and mitissimol A linoleate (5), were isolated
      from the fruiting bodies of Lactarius mitissimus. Their structures were
      elucidated on the basis of comprehensive spectroscopic techniques and necessary
      chemical methods. The relative stereochemistry of 1 was determined by single
      crystal X-ray diffraction analysis.

PMID- 16989535
TI  - Awajanomycin, a Cytotoxic gamma-lactone-delta-lactam metabolite from marine
      derived Acremonium sp. AWA16-1.
AB  - The new fungal metabolite awajanomycin (1), which has gamma-lactone-delta-lactam
      rings, was isolated from the marine-derived fungus Acremonium sp. AWA16-1, which
      had been collected from sea mud off Awajishima Island in Japan. The structure of
      1 was elucidated by spectroscopic analysis and chemical methods. Awajanomycin (1)
      and its derivative (2) inhibited the growth of A549 cells with IC(50) values of
      27.5 and 46.4 microg/mL, respectively.

PMID- 16989536
TI  - Depsidones from the endophytic fungus BCC 8616.
AB  - Three new depsidones (1-3) have been isolated from the endophytic fungus BCC 8616
      and their structures analyzed on the basis of spectroscopic data interpretation.
      Compound 1 exhibited weak cytotoxic activity against breast and epidermoid
      carcinoma cell lines.

PMID- 16989537
TI  - Prenylated phenolics from Ganoderma fornicatum.
AB  - Three new prenylated phenolic compounds, fornicins A-C (1-3), were obtained from
      the fruiting bodies of Ganoderma fornicatum. The structure elucidation was
      achieved by interpretation of spectroscopic data. These compounds exhibited
      moderate cytotoxic activity with IC(50) values of 15 to 30 microg/mL in Hep-2
      cells.

PMID- 16989538
TI  - Phytochemical constituents from Salsola tetrandra.
AB  - The new norisoprenoid 3beta-hydroxy-5alpha,6alpha-epoxy-beta-ionone-2alpha-O-beta
      d-glucopyranoside (1) and the long-chain hydroxy fatty acids 9,12,13
      trihydroxyoctadeca-10(E),15(Z)-dienoic acid (2) and 9,12,13-trihydroxyoctadeca
      10(E)-dienoic acid (3) were isolated from Salsola tetrandra aerial parts,
      together with 3,4,5-trimethoxyphenyl-beta-d-glucopyranoside (4), 9
      hydroxylinaloyl glucoside (5), taxiphyllin (6), trans-N-feruloyltyramine (7), and
      S-(-)-trans-N-feruloyloctopamine (8). Their structures were elucidated by
      extensive spectroscopic analysis and chemical methods. Compounds 6 and 8
      displayed mild antibacterial activity against Staphylococcus aureus, whereas
      compound 6 showed the highest activity in the Artemia salina bioassay.

PMID- 16989539
TI  - Phenolic glycosides with antioxidant activity from the stem bark of Populus
      davidiana.
AB  - Phytochemical study on the EtOAc-soluble fraction of the stem bark of Populus
      davidiana resulted in the isolation of 10 phenolic glycosides (1-10), which were
      identified on the basis of physicochemical and spectroscopic analyses. Among
      these, three new compounds, populosides A-C (1-3), were determined to be 2
      coumaroylmethyl-4-hydroxyphenyl-beta-D-glucopyranoside, 2-coumaroylmethylphenyl
      beta-D-glucopyranoside, and 2-feruoylmethylphenyl-beta-D-glucopyranoside,
      respectively. Compounds 1-10 were tested for their radical scavenging activity
      against an azo radical, ABTS*+. Of these, populosides A-C (1-3), populoside (4),
      grandidentatin (8), salireposide (9), and coumaroyl-beta-D-glucoside (10)
      exhibited antioxidant activity in this assay.

PMID- 16989540
TI  - Chaetocochins A-C, epipolythiodioxopiperazines from Chaetomium cochliodes.
AB  - Three new epipolythiodioxopiperazines, chaetocochins A (1), B (2), and C (3),
      along with dethio-tetra (methylthio) chetomin (4) and chetomin (5), were isolated
      from the ethyl acetate extract of the solid-state fermented rice culture of the
      fungus Chaetomium cochliodes. Their structures were elucidated on the basis of
      spectroscopic analysis. Compounds 1, 3, and 4 exhibited significant cytotoxicity
      in vitro against cancer cell lines Bre-04, Lu-04, and N-04.

PMID- 16989541
TI  - Geriatrics editorial policy on disclosures.

PMID- 16989542
TI  - Facial erythema with scale involving nose, lip folds. Daily shampooing does not
      relieve patient, who has history of Parkinson's disease.

PMID- 16989543
TI  - Long-term care of Parkinson's disease. Strategies for managing "wearing off"
      symptom re-emergence and dyskinesias.
AB  - Long-term care of elderly patients with Parkinson's disease (PD) is challenging
      for long-term care staff and physicians. Because the progression of PD varies
      among patients, an individualized treatment plan, updated as necessary based on
      disease progression, comorbid conditions, and side effects, is essential.
      Education regarding PD management is also needed to provide optimal care, and
      treatment guidelines from professional associations are available. Especially
      important is the management of motor complications, which usually emerge after
      treatment with antiparkinsonian medications, particularly levodopa/carbidopa.
      Current treatment strategies to avoid or treat motor complications aim at
      providing a more continuous (ie, physiologic) dopaminergic stimulation, rather
      than the pulsatile (intermittent) stimulation provided by traditional PD
      treatments. Catechol O-methyltransferase (COMT) inhibitors prolong the levodopa
      serum half-life and allow more levodopa to be delivered to the brain over a
      longer time, thereby smoothing dopaminergic stimulation. Dopamine agonists also
      provide more continuous dopaminergic stimulation but are associated with a
      greater likelihood of hallucinations and confusion, especially in the elderly.
      Treatments that reduce motor complications, allowing a higher level of
      functioning, lessen the burden of care in long-term care settings and increase
      quality of life for patients and their families.

PMID- 16989544
TI  - Small bowel bacterial overgrowth. An underrecognized cause of malnutrition in
      older adults.
AB  - Small bowel bacterial overgrowth (SBBO) is an important and under-recognized
      clinical syndrome in the elderly. It is the most common cause of malabsorption
      among older adults. Presentation of SBBO syndrome is often occult, which makes it
      imperative to maintain a high index of suspicion for this disorder. When
      symptomatic bacterial overgrowth is appropriately identified and treated there
      can be positive dramatic results. This article discusses the importance of
      considering a diagnosis of bacterial overgrowth in those predisposed to its
      development and the mechanisms by which nutrient malabsorption occurs. Signs and
      symptoms of bacterial overgrowth, differential diagnosis, investigation, and
      current treatment options are discussed.

PMID- 16989545
TI  - Quick minds don't blink: electrophysiological correlates of individual
      differences in attentional selection.
AB  - A well-established phenomenon in the study of attention is the attentional blink
      a deficit in reporting the second of two targets when it occurs 200-500 msec
      after the first. Although the effect has been shown to be robust in a variety of
      task conditions, not every individual participant shows the effect. We measured
      electroencephalographic activity for "nonblinkers" and "blinkers" during
      execution of a task in which two letters had to be detected in an sequential
      stream of digit distractors. Nonblinkers showed an earlier P3 peak, suggesting
      that they are quicker to consolidate information than are blinkers. Differences
      in frontal selection positivity were also found, such that nonblinkers showed a
      larger difference between target and distractor activation than did blinkers.
      Nonblinkers seem to extract target information better than blinkers do, allowing
      them to reject distractors more easily and leaving sufficient resources available
      to report both targets.

PMID- 16989546
TI  - Cue- versus probe-dependent prefrontal cortex activity during contextual
      remembering.
AB  - Functional neuroimaging comparisons of context and item memory frequently
      implicate the left prefrontal cortex (PFC) during the recovery of contextually
      specific memories. However, because cues and probes are often presented
      simultaneously, this activity could reflect operations involved in planning
      retrieval or instead reflect later operations dependent upon the memory probes
      themselves, such as evaluation of probe-evoked recollections. More importantly,
      planning-related activity, wherein subjects reinstate details outlining the
      nature of desired remembrances, should occur in response to contextual memory
      cues even before retrieval probes are available. Using event-related functional
      magnetic resonance imaging, we tested this by dissociating cue- from probe
      related activity during context memory for pictures. Cues forewarning contextual
      memory demands yielded more activity than those forewarning item memory in the
      left lateral precentral gyrus, midline superior frontal gyrus, and right
      frontopolar cortex. Thus, these anticipatory, cue-based activations indicated
      whether upcoming probe decisions would require contextually specific memories or
      not. In contrast, the left dorsolateral/midventrolateral and anterior
      ventrolateral PFC areas did not show differential activity until the probes were
      actually presented, demonstrating greater activity for context than for item
      memory probes. Direct comparison of proximal left PFC regions demonstrated
      qualitatively different response profiles across cue versus probe periods for
      lateral precentral versus dorsolateral regions. These results potentially isolate
      contextual memory-planning-related processes from subsequent processes such as
      the evaluation of recollections, which are necessarily dependent on individual
      probe features. They also demonstrate that contextual remembering recruits
      multiple, functionally distinct PFC processes.

PMID- 16989547
TI  - A reevaluation of the electrophysiological correlates of expert object
      processing.
AB  - Subordinate-level object processing is regarded as a hallmark of perceptual
      expertise. However, the relative contribution of subordinate- and basic-level
      category experience in the acquisition of perceptual expertise has not been
      clearly delineated. In this study, participants learned to classify wading birds
      and owls at either the basic (e.g., wading bird, owl) or the subordinate (e.g.,
      egret, snowy owl) level. After 6 days of training, behavioral results showed that
      subordinate-level but not basic-level training improved subordinate
      discrimination of trained exemplars, novel exemplars, and exemplars from novel
      species. Event-related potentials indicated that both basic- and subordinate
      level training enhanced the early N170 component, but only subordinate-level
      training amplified the later N250 component. These results are consistent with
      models positing separate basic and subordinate learning mechanisms, and, contrary
      to perspectives attempting to explain visual expertise solely in terms of
      subordinate-level processing, suggest that expertise enhances neural responses of
      both basic and subordinate processing.

PMID- 16989548
TI  - Inducing letter-by-letter dyslexia in normal readers.
AB  - Letter-by-letter (LBL) dyslexia is an acquired reading disorder characterized by
      very slow reading and a large linear word length effect. This suggests the use of
      a sequential LBL strategy, in sharp contrast with the parallel letter processing
      used by normal subjects. Recently, we have proposed that the reading difficulty
      of LBL dyslexics is due to a deficit in discriminating visually similar letters
      based on parallel letter processing [Arguin, M., Fiset, S., & Bub, D. Sequential
      and parallel letter processing in letter-by-letter dyslexia. Cognitive
      Neuropsychology, 19, 535-555, 2002]. The visual mechanisms underlying this
      deficit and the LBL strategy, however, are still unknown. In this article, we
      propose that LBL dyslexic patients have lost the ability to use, for parallel
      letter processing, the optimal spatial frequency band for letter and word
      recognition. We claim that, instead, they rely on lower spatial frequencies for
      parallel processing, that these lower spatial frequencies produce confusions
      between visually similar letters, and that the LBL compensatory strategy allows
      them to extract higher spatial frequencies. The LBL strategy would thus increase
      the spatial resolution of the visual system, effectively resolving the issue
      pertaining to between-letter similarity. In Experiments 1 and 2, we succeeded in
      replicating the main features characterizing LBL dyslexia by having normal
      individuals read low-contrast, high-pass-filtered words. Experiment 3, conducted
      in LBL dyslexic L.H., shows that, indeed, the letter confusability effect is
      based on low spatial frequencies, whereas this effect was not supported by high
      spatial frequencies.

PMID- 16989549
TI  - Lapses in a prefrontal-extrastriate preparatory attention network predict
      mistakes.
AB  - Mistakes are common to all forms of behavior but there is disagreement about what
      causes errors. We recorded electrophysiological and behavioral measures in a
      letter discrimination task to examine whether deficits in preparatory attention
      predicted subsequent response errors. Error trials were characterized by
      decreased frontal-central preparatory attention event-related potentials (ERPs)
      prior to stimulus presentation and decreased extrastriate sensory ERPs during
      visual processing. These findings indicate that transient lapses in a prefrontal
      extrastriate preparatory attention network can lead to response errors.

PMID- 16989550
TI  - Activation of preexisting and acquired face representations: the N250 event
      related potential as an index of face familiarity.
AB  - Electrophysiological studies using event-related potentials have demonstrated
      that face stimuli elicit a greater negative brain potential in right posterior
      recording sites 170 msec after stimulus onset (N170) relative to nonface stimuli.
      Results from repetition priming paradigms have shown that repeated exposures of
      familiar faces elicit a larger negative brainwave (N250r) at inferior temporal
      sites compared to repetitions of unfamiliar faces. However, less is known about
      the time course and learning conditions under which the N250 face representation
      is acquired. In the familiarization phase of the Joe/no Joe task, subjects
      studied a target "Joe" face ("Jane" for female subjects) and, during the course
      of the experiment, identified a series of sequentially presented faces as either
      Joe or not Joe. The critical stimulus conditions included the subject's own face,
      a same-sex Joe ( Jane) face and a same-sex "other" face. The main finding was
      that the subject's own face produced a focal negative deflection (N250) in
      posterior channels relative to nontarget faces. The task-relevant Joe target face
      was not differentiated from other nontarget faces in the first half of the
      experiment. However, in the second half, the Joe face produced an N250 response
      that was similar in magnitude to the own face. These findings suggest that the
      N250 indexes two types of face memories: a preexperimentally familiar face
      representation (i.e., the "own face" and a newly acquired face representation
      (i.e., the Joe/Jane face) that was formed during the course of the experiment.

PMID- 16989551
TI  - Specificity of action representations in the lateral occipitotemporal cortex.
AB  - The ability to recognize actions is important for cognitive development and
      social cognition. Areas in the lateral occipitotemporal cortex show increased
      activity when subjects view action sequences; however, whether this activity
      distinguishes between specific actions as necessary for action recognition is
      unclear. We used a functional magnetic resonance imaging adaptation paradigm to
      test for brain regions that exhibit action-specific activity. Subjects watched a
      series of action sequences in which the action performed or the person performing
      the action could be repeated from a previous scan. Three regions-the superior
      temporal sulcus (pSTS), human motion-sensitive cortex (MT/MST), and extrastriate
      body area (EBA)-showed decreased activity for previously seen actions, even when
      the actions were novel exemplars because the persons involved had not been seen
      previously. These action-specific adaptation effects provide compelling evidence
      that representations in the pSTS, MT/MST, and EBA abstract actions from the
      agents involved and distinguish between different particular actions.

PMID- 16989552
TI  - The involvement of the inferior parietal cortex in the numerical Stroop effect
      and the distance effect in a two-digit number comparison task.
AB  - The neural mechanism of number representation and processing is currently under
      extensive investigation. In this functional magnetic resonance imaging study, we
      designed a number comparison task to examine how people represent and compare two
      digit numbers in the brain, and whether they process the decade and unit digits
      in parallel. We manipulated the decade-unit-digit congruency and numerical
      distance between the pairs of numbers. We observed both Stroop-like interference
      and the distance effect in the participants' performance. People responded more
      slowly to incongruent pairs of numbers and pairs of a smaller distance. The
      inferior parietal cortex showed common and distinct patterns of activation for
      both attentional selection and number comparison processes, and its activity was
      modulated by the Stroop-like interference effect and the distance effect. Taken
      together, these results support both parallel and holistic comparison of two
      digit numbers in the brain.

PMID- 16989553
TI  - Electrophysiological correlates of retrieval processing: effects of consistent
      versus inconsistent retrieval demands.
AB  - Studies employing event-related potentials (ERPs) during tests of recognition
      memory have reported differences in neural activity elicited by new test items
      according to the specific demands of the retrieval task, such as retrieving
      studied words versus pictures. The present study investigated whether
      differential processing of new items is possible when retrieval demands vary
      unpredictably on a trial-by-trial basis. In separate study-test phases, subjects
      encoded lists of intermixed words and pictures, and undertook retrieval tests
      with words as test items. Each test item was preceded by a task cue that signaled
      whether subjects were to attempt to retrieve a word or a picture from the study
      list. In the "blocked"condition, the targeted study material remained constant
      throughout the test, whereas in the "mixed"condition, the targeted material
      varied unpredictably across trials. New-item ERPs were more positive-going when
      words rather than pictures were targeted in the "blocked" condition, replicating
      previous findings, but this effect was absent in the "mixed"condition. The
      findings are consistent with the hypothesis that differential processing of
      retrieval cues depends upon the adoption of different task sets ("retrieval
      orientations" that develop over multiple trials and cannot be adjusted merely in
      response to an instructional cue. Unlike the new-item ERPs, ERPs elicited by the
      task cues in the mixed condition differed according to targeted material, but
      only on trials when there was a switch between target material. The implications
      of these findings for understanding the different retrieval strategies engaged
      when retrieval demands are consistent versus inconsistent are discussed.

PMID- 16989554
TI  - Processing of musical syntax tonic versus subdominant: an event-related potential
      study.
AB  - The present study investigates the effect of a change in syntactic-like musical
      function on event-related brain potentials (ERPs). Eight-chord piano sequences
      were presented to musically expert and novice listeners. Instructed to watch a
      movie and to ignore the musical sequences, the participants had to react when a
      chord was played with a different instrument than the piano. Participants were
      not informed that the relevant manipulation was the musical function of the last
      chord (target) of the sequences. The target chord acted either as a syntactically
      stable tonic chord (i.e., a C major chord in the key of C major) or as a less
      syntactically stable subdominant chord (i.e., a C major chord in the key of G
      major). The critical aspect of the results related to the impact such a
      manipulation had on the ERPs. An N5-like frontal negative component was found to
      be larger for subdominant than for tonic chords and attained significance only in
      musically expert listeners. These findings suggest that the subdominant chord is
      more difficult to integrate with the previous context than the tonic chord (as
      indexing by the observed N5) and that the processing of a small change in musical
      function occurs in an automatic way in musically expert listeners. The present
      results are discussed in relation to previous studies investigating harmonic
      violations with ERPs.

PMID- 16989555
TI  - The role of the striatum in processing language rules: evidence from word
      perception in Huntington's disease.
AB  - On the assumption that linguistic faculties reflect both lexical storage in the
      temporal cortex and combinatorial rules in the striatal circuits, several authors
      have shown that striatal-damaged patients are impaired with conjugation rules
      while retaining lexical knowledge of irregular verbs [Teichmann, M., Dupoux, E.,
      Kouider, S., Brugieres, P., Boisse, M. F., Baudic, S., Cesaro, P., Peschanski,
      M., & Bachoud-Levi, A. C. (2005). The role of the striatum in rule application.
      The model of Huntington's disease at early stage. Brain, 128, 1155-1167; Ullman,
      M. T., Corkin, S., Coppola, M., Hickok, G., Growdon, J. H., Koroshetz, W. J., &
      Pinker, S. (1997). A neural dissociation within language: Evidence that the
      mental dictionary is part of declarative memory, and that grammatical rules are
      processed by the procedural system. Journal of Cognitive Neuroscience, 9, 266
      276]. Yet, such impairment was documented only with explicit conjugation tasks in
      the production domain. Little is known about whether it generalizes to other
      language modalities such as perception and whether it refers to implicit language
      processing or rather to intentional rule operations through executive functions.
      We investigated these issues by assessing perceptive processing of conjugated
      verb forms in a model of striatal dysfunction, namely, in Huntington's Disease
      (HD) at early stages. Rule application and lexical processes were evaluated in an
      explicit task (acceptability judgments on verb and nonword forms) and in an
      implicit task (lexical decision on frequency-manipulated verb forms). HD patients
      were also assessed in executive functions, and striatal atrophy was evaluated
      with magnetic resonance imaging (bicaudate ratio). Results from both tasks showed
      that HD patients were selectively impaired for rule application but lexical
      abilities were spared. Bicaudate ratios correlated with rule scores on both
      tasks, whereas executive parameters only correlated with scores on the explicit
      task. We argue that the striatum has a core function in linguistic rule
      application generalizing to perceptive aspects of morphological operations and
      pertaining to implicit language processes. In addition, we suggest that the
      striatum may enclose computational circuits that underpin explicit manipulation
      of regularities.

PMID- 16989556
TI  - Coming unbound: disrupting automatic integration of synesthetic color and
      graphemes by transcranial magnetic stimulation of the right parietal lobe.
AB  - In some individuals, a visually presented letter or number automatically evokes
      the perception of a specific color, an experience known as color-grapheme
      synesthesia. It has been suggested that parietal binding mechanisms play a role
      in the phenomenon. We used a noninvasive stimulation technique, transcranial
      magnetic stimulation (TMS), to determine whether the posterior parietal lobe is
      critical for the integration of color and shape in color-grapheme synesthesia, as
      it appears to be for normal color-shape binding. Using a color-naming task with
      colored letters that were either congruent or incongruent with the synesthetic
      photism, we demonstrate that inhibition of the right posterior parietal lobe with
      repetitive TMS transiently attenuates synesthetic binding. These findings suggest
      that synesthesia (the induction of color from shape) relies on similar mechanisms
      as found in normal perception (where the perception of color is induced by
      wavelength).

PMID- 16989557
TI  - Facilitating effect of 15-Hz repetitive transcranial magnetic stimulation on
      tactile perceptual learning.
AB  - Recent neuroimaging studies have revealed that tactile perceptual learning can
      lead to substantial reorganizational changes of the brain. We report here for the
      first time that combining high-frequency (15 Hz) repetitive transcranial magnetic
      stimulation (rTMS) over the primary somatosensory cortex (SI) with tactile
      discrimination training is capable of facilitating operant perceptual learning.
      Most notably, increasing the excitability of SI by 15-Hz rTMS improved perceptual
      learning in spatial, but not in temporal, discrimination tasks. These findings
      give causal support to recent correlative data obtained by functional magnetic
      resonance imaging studies indicating a differential role of SI in spatial and
      temporal discrimination learning. The introduced combination of rTMS and tactile
      discrimination training may provide new therapeutical potentials in facilitating
      neuropsychological rehabilitation of functional deficits after lesions of the
      somatosensory cortex.

PMID- 16989558
TI  - Neuroanatomical evidence for distinct cognitive and affective components of self.
AB  - This study examines whether the cognitive and affective components of self
      reflection can be dissociated using functional magnetic resonance imaging. Using
      a simple paradigm in which subjects judged the personal relevance of personality
      characteristics that were either favorable (e.g., "honest") or unfavorable (e.g.,
      "lazy", we found that distinct neural circuits in adjacent regions of the
      prefrontal cortex subserve cognitive and emotional aspects of self-reflection.
      The medial prefrontal cortex responded only to material that was self
      descriptive, and this did not differ as a function of the valence of the trait.
      When material was judged to be self-relevant, the valence of the material was
      resolved in an adjacent region of ventral anterior cingulate. The nature of self
      is one of the most enduring questions in science, and researchers are now
      beginning to be able to decompose the neural operations that give rise to a
      unitary sense of self.

PMID- 16989559
TI  - Contribution of familiarity and recollection to associative recognition memory:
      insights from event-related potentials.
AB  - Within the dual-process perspective of recognition memory, it has been claimed
      that familiarity is sufficient to support recognition of single items, but
      recollection is necessary for associative recognition of item pairs. However,
      there are some reports suggesting that familiarity might support associative
      recognition judgments when the items form an easy to access bound representation.
      In contrast, recollection seems to be required for the recognition of bindings
      that might be flexibly rearranged in novel situations. We investigated whether
      both forms of binding are mediated by different mechanisms as reflected by a
      qualitatively different spatiotemporal eventrelated potential (ERP) pattern. In a
      recognition memory experiment, subjects gave old/new judgments to words learned
      by focusing either on interitem associations or on size relation of word
      triplets. Results revealed higher hit rates in the relational condition as
      compared to the associative condition. In addition, the proportion of triplets
      from which all three items were remembered was significantly larger in the
      relational condition suggesting that memory retrieval in this condition relies
      primarily on bound representations of word triplets. The ERP revealed a late
      parietal old/new effect for both conditions, with relational processing resulting
      in a greater effect. In contrast, an early frontal old/new effect was solely
      present in the associative condition. Taken together, these data provide evidence
      that familiarity might support associative recognition if the associated
      components are coherently encoded into a bound representation. Recollection might
      foster the recognition of relational bindings among items. This indicates that
      the contribution of familiarity and recollection to associative recognition
      depends on the kind of binding operations performed on the items rather than on
      the single versus multiple item distinction.

PMID- 16989561
TI  - Seroprevalence rates and transmission of plague (Yersinia pestis) in mammalian
      carnivores.
AB  - Exposure to plague (Yersinia pestis) by flea-bites or consumption of infected
      rodents is common in mammalian carnivores in North America. Most carnivore
      species exhibit seroprevalence rates ranging from 3% to 100% in areas where
      plague occurs. Seroprevalence is highest in mustelids, intermediate in ursids,
      felids, and canids, and lowest in procyonids, probably reflecting variation in
      exposure rates as a function of dietary habits. Although conventional wisdom
      suggests that carnivores may only be important in plague ecology as vectors of
      infective fleas, animal-to-human (zoonotic) transmission suggests that mammalian
      carnivores can act as infectious hosts. Furthermore, a review of clinical
      investigations reveals that plague can be harvested from canid and felid hosts,
      and suggests the possibility of plague transmission between carnivores. Further
      study of plague transmission by carnivores in both wild and laboratory conditions
      is needed to understand the possible role of carnivores as wildlife reservoirs of
      plague.

PMID- 16989562
TI  - The root-vole Microtus oeconomus (Pallas, 1776): a new potential reservoir of
      Anaplasma phagocytophilum.
AB  - Anaplasma phagocytophilum infection is a recently emerged tick-borne zoonosis.
      The bacterium's reservoirs likely comprise cervids, some ruminants, rodents, and
      perhaps other small and intermediate-size mammals; the main vector in Europe is
      the Ixodes ricinus tick. The Bialowieza Primeval Forest is an ecosystem with a
      known prevalence of tick-borne pathogens. We studied the root-vole Microtus
      oeconomus to evaluate the natural infection of A. phagocytophilum.
      Intragranulocytic bacterial clusters (morulae) were not seen, but the A.
      phagocytophilum-specific nested polymerase chain reaction (PCR) product,
      targeting the rrs gene, was detected in two out of 30 rodent samples (GenBank
      accession nos. DQ361024 and DQ361025). Twenty-six root vole (86.6%) hosted ticks,
      mainly Dermacentor reticulatus larvae and nymphs. Only two rodents were
      parasitazed by I. ricinus single larvae. These data show the presence of natural
      infection of A. phagocytophilum among the root-vole M. oeconomus in the
      Bialowieza Primeval Forest ecosystem.

PMID- 16989563
TI  - Serologic evidence for Rickettsia typhi and an ehrlichial agent in Norway rats
      from Baltimore, Maryland, USA.
AB  - We screened serum from 90 Norway rats trapped in East Baltimore, Maryland, USA,
      from April to November 2005 for antibodies against Rickettsia typhi and Ehrlichia
      chaffeensis. Six rats had positive titers of > or = 1:64 against R. typhi and did
      not react with R. akari. In addition, four rats had cross-reactive antibodies
      with titers of > or = 1:64 against Ehrlichia chaffeensis. Sera from these rats
      also cross-reacted with Anaplasma phagocytophilum or Ehrlichia muris. Our data
      indicate that the agent of murine typhus and ehrlichial agents are circulating in
      the Norway rat population in Baltimore.

PMID- 16989564
TI  - Role of California (Callipepla californica) and Gambel's (Callipepla gambelii)
      quail in the ecology of mosquito-borne encephalitis viruses in California, USA.
AB  - Gambel's and California quail were infected repeatedly whenever western equine
      encephalomyelitis virus (WEEV), St. Louis encephalitis virus (SLEV), and (WNV)
      West Nile virus were active during summer in California. The timing of virus
      appearance and quail infection coincided well with the appearance of chicks in
      nature, leading us to hypothesize that large coveys containing these non-immune
      birds could be important in focal virus amplification in rural settings. However,
      experimental infection studies with chicks, juveniles, and adults of both quail
      species using sympatric strains of WEEV, SLEV, and WNV indicated that only
      immature birds were competent hosts for WEEV, producing viremias sufficiently
      elevated to efficiently infect Culex tarsalis mosquitoes. Quail were less
      competent hosts for WNV and were incompetent for SLEV. Large populations of quail
      that frequently are infected with SLEV or WNV, but produce low to moderate
      viremias, may serve as dead end hosts for these viruses. Due to their abundance
      and repeated infection, these birds may attenuate virus amplification in rural
      areas of California and possibly could be one reason why WNV epidemics seem to
      occur more frequently in urban and periurban than in rural landscapes.

PMID- 16989565
TI  - Antibodies to West Nile virus in feral swine from Florida, Georgia, and Texas,
      USA.
AB  - West Nile virus (WNV) exposure has not yet been reported in feral swine (Sus
      scrofa) despite the broad geographic range and population density of this
      species. The objectives of this study were to determine the prevalence of
      antibodies to WNV in feral pigs, and to evaluate serologic diagnostics as applied
      to this species. Feral pig serum from three states was evaluated for antibodies
      to WNV. The overall WNV seroprevalence rate for 222 samples collected in 2001
      2004 was 22.5%. Seroprevalence rates in Florida, Georgia, and Texas were 17.2%,
      26.3%, and 20.5%, respectively. The results of this study demonstrate that feral
      pigs could represent useful mammalian sentinels of WNV.

PMID- 16989566
TI  - Cats and goat whey associated with Toxoplasma gondii infection in pigs.
AB  - In organic livestock production systems, farm-management factors are thought to
      play an important role in the on-farm prevalence of Toxoplasma gondii.
      Serological results and the results of an HACCP analysis were combined to
      determine important risk factors for the prevalence of this protozoan parasite.
      Mathematical analysis demonstrated that feeding goat whey to pigs and the
      presence of a high number of cats were positively correlated to T. gondii
      seroprevalence in pigs. Not covering roughage and the farmers' assumption that
      pigs can come into contact with cat feces also showed a positive relationship. In
      order to decrease the risk of T. gondii infecting their pigs, farmers should
      limit the access and number of cats on their farms and refrain from feeding goat
      whey to their pigs.

PMID- 16989567
TI  - Serosurveillance for Anaplasma phagocytophilum antibodies in white-tailed deer
      (Odocoileus virginianus) in Iowa, USA.
AB  - Cases of human granulocytic anaplasmosis have increased in number and are being
      identified in new geographic areas since its discovery in 1994. White-tailed deer
      (WTD) become infected with the causative agent, Anaplasma phagocytophilum, and
      serve as natural sentinels for this organism. In order to determine if A.
      phagocytophilum is present in the state of Iowa, sera collected from 628 WTD in
      2004 from 13 sites and from 282 WTD in 1999 from a single, common site were
      tested by enzyme-linked immunosorbent assay and Western immunoblotting. A
      seroprevalence of 9.1% was found among the 2004 samples, and there was no change
      in seropositivity rates from 1999 to 2004 at the single, common site. As A.
      phagocytophilum is another tick-borne human pathogen to be identified in the
      state of Iowa, this study has important implications for health care providers.

PMID- 16989568
TI  - Modeling the spatial distribution of mosquito vectors for West Nile virus in
      Connecticut, USA.
AB  - The risk of transmission of West Nile virus (WNV) to humans is associated with
      the density of infected vector mosquitoes in a given area. Current technology for
      estimating vector distribution and abundance is primarily based on Centers for
      Disease Control and Prevention (CDC) light trap collections, which provide only
      point data. In order to estimate mosquito abundance in areas not sampled by
      traps, we developed logistic regression models for five mosquito species
      implicated as the most likely vectors of WNV in Connecticut. Using data from 32
      traps in Fairfield County from 2001 to 2003, the models were developed to predict
      high and low abundance for every 30 x 30 m pixel in the County. They were then
      tested with an independent dataset from 16 traps in adjacent New Haven County.
      Environmental predictors of abundance were extracted from remotely sensed data.
      The best predictive models included non-forested areas for Culex pipiens, surface
      water and distance to estuaries for Cx. salinarius, surface water and
      grasslands/agriculture for Aedes vexans and seasonal difference in the normalized
      difference vegetation index and distance to palustrine habitats for Culiseta
      melanura. No significant predictors were found for Cx. restuans. The sensitivity
      of the models ranged from 75% to 87.5% and the specificity from 75% to 93.8%. In
      New Haven County, the models correctly classified 81.3% of the traps for Cx.
      pipiens, 75.0% for Cx. salinarius, 62.5% for Ae. vexans, and 75.0% for Cs.
      melanura. Continuous surface maps of habitat suitability were generated for each
      species for both counties, which could contribute to future surveillance and
      intervention activities.

PMID- 16989569
TI  - Borrelia afzelii gene expression in Ixodes ricinus (Acari: Ixodidae) ticks.
AB  - Spirochetes belonging to the Borrelia burgdorferi sensu lato (s. l.) complex have
      evolved remarkable ability to survive in diverse ecological niches during
      transmission cycles between ticks and vertebrate hosts by variable gene
      expression. To understand the events during spirochete transmission from feeding
      ticks to hosts, mRNA levels of selected B. afzelii genes (bbk32, dbpA, ospA, ospC
      and vlsE) were measured by quantitative real-time SYBR Green PCR. B. afzelii
      infected Ixodes ricinus nymphs fed on laboratory BALB/c mice for 0, 24, 48, and
      72 hours. The mRNA levels of the constantly expressed flagellin gene were used
      for the relative quantification of selected genes. Differences in gene expression
      profiles were observed in unfed ticks and during tick feeding. mRNA levels of
      bbk32 and dbpA showed distinctive decreasing patterns during the first 24 hours
      post-attachment, while ospC and vlsE mRNA levels increased significantly during
      the feeding process. In contrast, ospA levels decreased for the 48 hours of tick
      feeding and slightly increased by 72 hours. More detailed and comprehensive
      studies on regulation of gene expression in different Borellia genospecies on the
      vector-host interface would aid to develop effective strategies in preventing
      pathogen transmission.

PMID- 16989570
TI  - West Nile virus antibody prevalence in red-winged blackbirds (Agelaius
      phoeniceus) from North Dakota, USA (2003-2004).
AB  - This study was designed to explore the role that red-winged blackbirds (Agelaius
      phoeniceus) may have played in disseminating West Nile virus (WNV) across the
      United States. Using enzyme-linked immunosorbent assays designed to detect WNV
      antibodies in avian species we were able to determine the WNV antibody prevalence
      in a cohort of red-winged blackbirds in central North Dakota in 2003 and 2004.
      The peak WNV antibody prevalence was 22.0% in August of 2003 and 18.3% in July of
      2004. The results of this study suggest that red-winged blackbird migratory
      populations may be an important viral dispersal mechanism with the ability to
      spread arboviruses such as WNV across the United States.

PMID- 16989571
TI  - Interview with Robert B. Tesh, M.D. by Vicki Glaser.

PMID- 16989572
TI  - Antioxidant and antibacterial genes are upregulated in early involution of the
      mouse mammary gland: sharp increase of ceruloplasmin and lactoferrin in
      accumulating breast milk.
AB  - The mammary gland develops mainly after birth, and shows a repeated cycle of
      pregnancy-triggered proliferation, differentiation for lactation, and a
      regressive phase after weaning known as involution. Compared to the proliferation
      and differentiation phases, the molecular mechanisms of involution are largely
      unknown. In the present study we screened genes that could play a potential role
      in early involution of the mouse mammary gland using fluorescent differential
      display followed by gene-specific reverse transcription-polymerase chain
      reaction. We found that five genes were upregulated more than twofold 48 h after
      weaning: ceruloplasmin, chemokine (CXC motif) ligand 4, epoxide hydrolase 1,
      lactoferrin, and properdin P factor. The products of these genes can be linked to
      defense against oxidative stress and/or infectious bacteria. Electrophoretic
      analysis and mass spectrometry of milk proteins showed that the concentrations of
      ceruloplasmin and lactoferrin in milk were increased fivefold and more than 38
      fold, respectively, within 48 h after weaning. These increases were in contrast
      to the constant presence of other major proteins including albumin, caseins,
      transferrin, and whey acidic protein. Ceruloplasmin and lactoferrin may cooperate
      in the defense of the mammary gland in the postlactation period.

PMID- 16989573
TI  - Organizational and expressional uniqueness of a testis-specific mRNA transcript
      of protooncogene c-kit receptor in water buffalo Bubalus bubalis.
AB  - Protooncogene c-kit receptor is implicated with spermatogenesis, melanogenesis,
      and hematopoeisis, and undergoes tissue/stage specific alternate splicing. We
      have isolated 2973-bp full-length cDNA sequence (CDS) of this gene from testis
      and other tissues of water buffalo Bubalus bubalis. Upon comparison, the c-kit
      sequences showed tissue specific nucleotide changes resulting in novel truncated
      peptides. These peptides lacked intracellular and/or transmembrane domains in all
      the tissues except testis. Other alternately spliced tissue-specific transcripts
      were also detected, which are the integral parts of the open reading frame and
      have been reported in other mammals. Phylogenetic analysis of the sequences
      revealed unique tyrosine kinase domain in buffalo. Copy number calculation and
      expressional analysis of c-kit using real-time PCR established its single copy
      status and highest expression (137-177 folds) in testis compared to that (least)
      in liver. c-kit expression was detected in semen samples although 10 times lesser
      compared to that in testis. The highest expression of c-kit in testis and the
      presence of mRNA transcript in sperms substantiate its predominant role in
      spermatogenesis. This study establishes unequivocal involvement of an autosomal
      gene c-kit receptor in testicular function.

PMID- 16989574
TI  - Myoseverin is a potential angiogenesis inhibitor by inhibiting endothelial cell
      function and endothelial progenitor cell differentiation.
AB  - Myoseverin, a new microtubule-binding molecule, acts reversibly on myoblast
      proliferation without the cytotoxic effects displayed by nonpurine-based
      microtubule-disrupting molecules, like taxol, vinblastine, nocodazole, and the
      colchicines. In this study, we examined the effects of myoseverin on in vitro
      function of endothelial cells and endothelial progenitor cell differentiation in
      order to explore the possibility for the application of myoseverin as a
      reversible antiangiogenic agent. Myoseverin potently inhibited proliferation of
      human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner with
      an IC50 of approximately 8 microM. When myoseverin was removed after treatment
      for 3 days, all the cells pretreated at a concentration range of 2.5-80 microM
      resumed the cell growth. It also inhibited VEGF-induced HUVEC migration dose
      dependently. When mononuclear cells (MNCs) isolated from human cord blood were
      cultured on fibronectin-coated plates for 7 days, myoseverin decreased the number
      of adherent cells in a dose-dependent manner with IC50 of approximately 9 microM.
      It also suppressed the development of ac-LDL uptake ability as well as the
      expression of endothelial lineage markers, KDR, CD31, and vWF. Finally, it
      inhibited formation of HUVECs or ex vivo cultivated EPCs into capillary-like
      structure on Matri-gel and in vivo angiogenesis on the chick chorioallantoic
      membrane. Therefore, these results suggest that myoseverin can be effectively
      used for the inhibition of new vessel growth by inhibiting endothelial cell
      function and differentiation of progenitor cells.

PMID- 16989575
TI  - PTX1(ERGIC2)-VP22 fusion protein upregulates interferon-beta in prostate cancer
      cell line PC-3.
AB  - PTX1 is a gene identified by subtractive hybridization on the basis that it is
      expressed in normal prostate and not in prostate carcinoma. It is unrelated to
      the pituitary homeobox protein (Ptx1 or Pitx1), which regulates pituitary hormone
      gene expression, and its function is currently unknown. Recently, it was found to
      be a homolog of the yeast Erv41p, an endoplasmic reticulum (ER) resident protein
      involved in protein trafficking between ER and Golgi, and was renamed as ERGIC2.
      Ectopic expression of a partial sequence of PTX1 (Met84 - Leu225) as a VP22
      fusion protein in prostate cancer cell line, PC-3, induced cellular senescence.
      Gene expression microarray analyses showed that interferon-beta (IFN-beta) and a
      number of IFN-inducible genes, among other genes, were upregulated by the PTX1
      VP22 fusion protein. Upregulation of IFN-beta was confirmed by RTPCR and promoter
      reporter assay. However, the upregulation of IFN-beta by the PTX1-VP22 fusion
      protein was not due to nuclear translocation of the PTX1 luminal domain.

PMID- 16989576
TI  - The extracellular domain of p185(c-neu) induces density-dependent inhibition of
      cell growth in malignant mesothelioma cells and reduces growth of mesothelioma in
      vivo.
AB  - EGFR is involved in the density-dependent inhibition of cell growth, while
      coexpression of EGFR with erbB2 can render normal cells transformed. In this
      study, we have examined the effect of a species of p185 that contains the
      transmembrane domain and the extracellular domain of p185(c-neu), on growth
      properties of a human malignant mesothelioma cell line that coexpresses EGFR and
      erbB2. The ectodomain form of p185(c-neu) enhanced density-dependent inhibition
      of cell growth and we found that p21 induction appeared to be responsible for
      this inhibitory effect. Previously, the extracellular domain species was shown to
      suppress the transforming abilities of EGFR and p185(c-neu/erbB2) in a dominant
      negative manner. The ability of this subdomain to affect tumor growth is
      significant, as it reduced in vivo tumor growth. Unexpectedly, we found that the
      domain did not abrogate all of EGFR functions. We noted that EGFR-induced density
      dependent inhibition of cell growth was retained. Tyrosine kinase inhibitors of
      EGFR did not cause density-dependent inhibition of cell growth of malignant
      mesothelioma cells. Therefore, simultaneously inhibiting the malignant phenotype
      and inducing density-dependent inhibition of cell growth in malignant
      mesothelioma cells by the extracellular domain of p185(c-neu) may represent an
      important therapeutic advance.

PMID- 16989577
TI  - Linear connection of condensing chromosomes in nuclei of synchronized CHO cells.
AB  - Reversibly permeabilized cells allowed the analysis of intermediates of large
      scale chomatin condensation in a cell cycle-dependent manner. This paper
      summarizes major intermediates of chromatin condensation and visualizes
      connectivity between different forms of chromosomes. At the early S phase the
      veil-like fibrillary chromatin is supercoiled to form chromatin bodies
      representing the earliest visible chromosomes. Supercoiling results in a
      chromatin fiber, which turns to rope (thick fiber) forming loops and chromatin
      ribbon. The elongated shape of prechromosomes indicates that they are arranged
      head to tail. Bent forms (loop, c-, and v-shaped structures) of interphase
      chromosomes open at the end of S phase. Linear arrangement of chromosomes was
      observed to the end of the condensation process, suggesting that connectivity of
      chromosomes is maintained throughout the cell cycle.

PMID- 16989578
TI  - Natural killer cells: from bench to cancer therapy.
AB  - Natural killer (NK) cells are effectors of the innate immune system that play an
      important role in host response against viruses and tumour cells through the
      production of cytokines and direct cytolytic activity. There has been limited
      success reported from clinical trials in cancer patients treated with activated
      NK cells. Over the last decade, a better understanding of the biology of NK
      cells, NK cell receptors and the role of interleukin-15 has led to the
      development of new strategies using NK cells as immunotherapy for cancer
      treatment in the transplant and non-transplant settings.

PMID- 16989579
TI  - Combining cell therapy and nanotechnology.
AB  - Cell transplantation to treat diseases characterised by tissue and cell
      dysfunction, ranging from diabetes to spinal cord injury, has made great strides
      preclinically and towards clinical efficacy. In order to enhance clinical
      outcomes, research needs to continue in areas including the development of a
      universal cell source that can be differentiated into specific cellular
      phenotypes, methods to protect the transplanted allogeneic or xenogeneic cells
      from rejection by the host immune system, techniques to enhance cellular
      integration of the transplant within the host tissue, strategies for in vivo
      detection and monitoring of the cellular implants, and new techniques to deliver
      genes to cells without eliciting a host immune response. Overcoming these
      obstacles will be of considerable benefit, as it allows understanding,
      visualising and controlling cellular interactions at a submicron level.
      Nanotechnology is a multidisciplinary field that allows us to manipulate
      materials, tissues, cells and DNA at the level of and within the individual cell.
      As such, nanotechnology may be well suited to optimise the generally encouraging
      results already achieved in cell transplantation. This review presents some of
      the ways that nanotechnology can directly contribute to cell transplantation.

PMID- 16989580
TI  - Haematopoietic stem and progenitor cell-targeted therapies for thrombocytopenia.
AB  - This review discusses the present outlook for new thrombocytopenia therapies that
      induce haematopoietic stem and progenitor cells to proliferate, differentiate and
      produce functional platelets. A brief overview of megakaryopoiesis and its
      regulation by thrombopoietin (TPO) is followed by a discussion of how early
      experience with recombinant TPO therapies stimulated the search for novel TPO
      receptor ligands. A summary is then provided of the results of Phase I clinical
      trials with the new small molecule and peptide TPO mimetics that are in
      development at present. Finally, recent developments in the ex vivo expansion of
      primitive haematopoietic cells and the potential enhancement of cell-based
      therapies by haematopoietic growth factors in vivo are briefly summarised as part
      of a look towards the future.

PMID- 16989581
TI  - The status of liver transplantation for hepatitis C.
AB  - The hepatitis C virus (HCV) infects 3% of the world's population, or
      approximately 170 million people. Most of those acutely infected progress to
      chronic infection and are unresponsive to existing antiviral treatment. Over a 20
      year period, chronic HCV infection leads to cirrhosis and the sequelae of end
      stage liver disease, including hepatic encephalopathy, ascites, variceal
      haemorrhage and hepatocellular carcinoma. Orthotopic liver transplantation (OLT)
      is the optimal treatment for decompensated HCV cirrhosis, but is limited by organ
      availability and universal graft reinfection. This review discusses the results
      with OLT for HCV from the Dumont-UCLA Liver Transplant Center and discusses
      future directions in the management of HCV.

PMID- 16989582
TI  - CD4+CD25+ regulatory T cell therapy for the induction of donor-specific clinical
      transplantation tolerance.
AB  - Naturally occurring CD4+CD25+ regulatory T cells (Tregs) have been shown to play
      a key role in the control of autoimmunity. Interestingly, they are also capable
      of mediating transplantation tolerance and they can have indirect allospecificity
      for donor antigens. An increasing body of evidence in experimental studies has
      indicated that adoptive transfer of in vitro expanded CD4+CD25+ Tregs with
      indirect antidonor allospecificity can induce long-term donor-specific
      transplantation tolerance. Thus, adoptive cell therapy using patient-specific
      CD4+CD25+ Tregs as individualised medicine to promote clinical transplantation
      tolerance is promising.

PMID- 16989583
TI  - Advances and potential treatment for Philadelphia chromosome-positive adult acute
      lymphoid leukaemia.
AB  - Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) is the
      most common subtype of ALL in adults. Conventional chemotherapy-based approaches
      that are effective in other precursor B cell ALL cases have a poor chances of
      cure in patients with a Ph+ diagnosis. Therefore, allogeneic stem cell
      transplantation performed during the first remission is the recommended therapy.
      Recently, the availability of imatinib mesylate and other tyrosine kinase
      inhibitors and small molecules that affect the BCR/ABL signalling pathways has
      introduced a new therapeutic opportunity, and could change the treatment paradigm
      and prognosis for these patients. In this article, the results from clinical
      trials using imatinib in relapsed/refractory patients and as front-line therapy
      are described. In addition, preliminary experiences with novel tyrosine kinase
      inhibitors in imatinib-resistant Ph+ ALL are discussed.

PMID- 16989584
TI  - Genetic engineering for haemophilia A.
AB  - At first sight, haemophilia A would appear to be an ideal candidate for treatment
      by gene therapy. There is a single gene defect; cells in different parts of the
      body, but especially the liver, produce Factor VIII, and only 5% of normal levels
      of Factor VIII are necessary to prevent the serious symptoms of bleeding. This
      review attempts to outline the status of gene therapy at present and efforts that
      have been made to overcome the difficulties and remaining problems that require
      solving. Undoubtedly, success will be achieved, but it is likely that
      considerably more work will be necessary before experimental models can be
      introduced into the clinic with any likelihood of success. The most successful
      results in animals that may have clinical application were from introducing the
      Factor VIII gene to newborn animals before antibodies are produced, presumably
      inducing a state of tolerance.

PMID- 16989585
TI  - Telomerase-based immunotherapy of cancer.
AB  - The progression from the cloning of human telomerase reverse transcriptase
      (hTERT) in 1997 to the first clinical trials of hTERT as an antitumour
      immunotherapy target has been swift. hTERT is overexpressed in the vast majority
      of human cancers yet has limited expression in normal adult tissue. It plays a
      critical role in oncogenesis and may be expressed by cancer stem cells. However,
      despite being a self antigen, hTERT is immunogenic both in vitro and in vivo.
      Several Phase I studies of hTERT immunotherapy have been completed in patients
      with breast, prostate, lung and other cancers, and clinical and immunological
      results are encouraging. Immunotherapy induces functional, antitumour T cells in
      patients in the absence of clinical toxicity. The opportunity for vaccinating
      individuals as an immunoprevention strategy can also be envisioned for hTERT
      based therapies.

PMID- 16989586
TI  - RANK ligand inhibition with denosumab for the management of osteoporosis.
AB  - Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine member
      of the tumour necrosis factor family that is the principal final mediator of
      osteoclastic bone resorption. It plays a major role in the pathogenesis of
      postmenopausal osteoporosis, as well bone loss associated with rheumatoid
      arthritis, metastatic cancer, multiple myeloma, aromatase inhibitor therapy and
      androgen deprivation therapy. Denosumab (AMG 162) is an investigational fully
      human monoclonal antibody with a high affinity and specificity for RANKL. By
      inhibiting the action of RANKL, denosumab reduces the differentiation, activity
      and survival of osteoclasts, thereby slowing the rate of bone resorption.
      Denosumab has been shown to increase bone mineral density (BMD) and reduce bone
      turnover in postmenopausal women with low BMD. Denosumab is a potential treatment
      for osteoporosis and other skeletal disorders.

PMID- 16989587
TI  - Interferon-gamma 1b for the treatment of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) represents a particularly aggressive disease,
      the aetiology of which still remains unknown. The natural history of the disease
      often leads to respiratory failure and death, with a mortality rate greater than
      some cancers. To date, no management approach has proven to be efficacious for
      the treatment of this disease. IPF has been characterised as an 'epithelial
      fibroblastic disorder', characterised by abnormal wound healing with excessive
      fibrosis and minimal inflammation. These emerging data have focused attention on
      antifibrotic drugs. Interferon-gamma1b (IFN-gamma1b) has recently been proposed
      as a promising candidate for the treatment of IPF. The reason for this is that
      IFN-gamma1b has the ability to modulate the Th1/Th2 imbalance and to suppress
      fibroblast activation. The view that IPF is untreatable at present requires
      reconsideration, as improved survival has been suggested in three controlled
      trials of IFN-gamma1b in IPF therapy.

PMID- 16989588
TI  - World Transplant Congress. Boston, Massachusetts, USA, 22-27 July 2006.
AB  - The World Transplant Congress (WTC) is the first joint international transplant
      meeting co-organised by the Transplantation Society, the American Society of
      Transplantation (AST) and the American Society of Transplant Surgeons (ASTS). It
      was the first meeting of this calibre that was being held by three world-renowned
      authorities in the field of transplantation. Under the direction of the congress
      president, AB Cosimi, the attendance of this meeting is a 'must' for all working
      in the field of transplantation. The congress had provided an important forum for
      the exchange of new scientific and clinical information that is relevant to solid
      organ and tissue transplantation. In addition, it also created an arena for the
      interchange of ideas regarding the care and management of transplant recipients.
      There were many sessions that were engineered in order to facilitate the
      discussion of socioeconomic, ethical and regulatory issues related
      transplantation. On the whole, the meeting has set a very high standard for any
      future transplant congresses to match-providing the delegates with updates on
      transplantation with the new scientific prospectives in T cell costimulation,
      innate immunity (dendritic cells), anatomy of immune response and regulatory T
      cell biology. More importantly, it has highlighted the potentials of harnessing
      these new findings for future biological therapies in preventing rejection and
      inducing tolerance.

PMID- 16989589
TI  - The (pro)renin receptor: therapeutic consequences.
AB  - It is generally assumed that the beneficial effects of renin-angiotensin system
      blockers in cardiovascular disease are due to blockade of the generation or
      action of angiotensin at tissue sites. Such generation depends on the uptake of
      renin and/or its inactive precursor prorenin from the circulation. Recently, a
      (pro)renin receptor has been cloned that might perform this task. Unexpectedly,
      this receptor also induced angiotensin-independent effects, suggesting that renin
      and/or prorenin may act as agonists for this receptor. Ultimately, this could
      lead to the development of (pro)renin receptor blockers (i.e., drugs that not
      only prevent tissue angiotensin generation but also inhibit renin- or prorenin
      induced effects).

PMID- 16989590
TI  - Prorenin receptor blockers: effects on cardiovascular complications of diabetes
      and hypertension.
AB  - When the 'handle region' of the prorenin prosegment interacts with the (pro)renin
      receptor, the prorenin molecule partially changes the conformation to an
      enzymatically active state. On the other hand, the receptor triggers its own
      intracellular signalling pathways independent of the renin-angiotensin system
      (RAS). The 'handle region' peptide competitively binds to the receptor as a decoy
      peptide and inhibits both the non-proteolytic activation of prorenin and the RAS
      independent intracellular signals. Therefore, prorenin receptor blockers
      including the decoy peptide may have superior benefits on end-organ damage in
      diabetes and hypertension compared with conventional RAS inhibitors.

PMID- 16989591
TI  - Future trends in human brucellosis treatment.
AB  - The global burden of human brucellosis remains enormous. Existing treatment
      options, largely based on experience gained > 30 years ago, are adequate but not
      optimal. The evolving understanding of the pathophysiology of the disease may
      augment in designing and evaluating alternative approaches that may prove to be
      superior. Current alternative approaches such as co-trimoxazole-containing
      regimens, should be widely evaluated as being more cost-effective. New methods of
      delivery such as gentamicin-loaded microparticles, neutralisation of the
      environment where Brucella resides and use of novel antibiotics such as
      tigecycline may be of importance in the future. The role of immunomodulation,
      widely but inconsistently applied in 'chronic' brucellosis, should be further
      evaluated in all disease stages to define if it is of any use. The development of
      a subcellular vaccine would be an important step forward although one has to take
      into account the multiple interactions between Brucella and the immune system,
      various technical problems and the lack of funds. Reviewing existing attempts at
      the development of such a vaccine, the authors conclude that a trivalent
      subcellular vaccine may be needed for adequate efficacy.

PMID- 16989592
TI  - Intensive statin therapy for treating acute coronary syndromes.
AB  - The long-term efficacy of statins for the primary and secondary prevention of
      coronary heart disease is well established; however, until recently, there was
      little trial-based evidence to support the early clinical benefit of these agents
      after acute coronary syndromes (ACS). This is particularly important as ACS is
      characterised by a high rate of recurrent early events in the first 6 months and
      (traditionally) lipid-lowering therapy was perceived to reduce coronary heart
      disease risk by lowering the significant risk of elevated cholesterol over many
      years. This paper reviews the current state of evidence from the key statin
      trials in ACS and their implications for the future management of ACS.

PMID- 16989593
TI  - Investigating prophylactic botulinum toxin type A for chronic headache disorders.
AB  - There is an increasing number of studies on botulinum toxin A in the treatment of
      idiopathic and symptomatic headache; however, many studies can hardly be compared
      with each other because of different end points and different trial designs. For
      the prophylactic treatment of tension-type headache, migraine and cervicogenic
      headache, no sufficient positive evidence for a successful treatment can be
      obtained from the randomised, double-blind and placebo-controlled trials
      performed so far. For the treatment of chronic daily headache (including
      medication-overuse headache), there is inconsistent positive evidence for
      subgroups (e.g., patients without other prophylactic treatment). This means that
      most of the double-blind and placebo-controlled studies do not confirm the
      assumption that botulinum toxin A is efficacious in the treatment of idiopathic
      headache disorders; however, it is possible that some subgroups of patients with
      chronic migraine benefit from a long-term treatment for > or = 6 months.

PMID- 16989594
TI  - Novel anticonvulsant drugs targeting voltage-dependent ion channels.
AB  - Epilepsy is one of the most common neurological disorders with a prevalence of
      0.5-1%. About two-thirds of epilepsy patients respond well to anticonvulsant
      pharmacotherapy and become seizure free. There is a third who remain
      pharmacoresistant, demonstrating the pressing need for novel treatment options
      that could be drugs with a different mechanism of action compared with those that
      are currently in clinical use. During the past, many new substances have been
      screened for blocking or activating effects on specific ion channels,
      particularly those that are not targets for currently used antiepileptic drugs.
      This review provides an overview of new anticonvulsant compounds targeting
      voltage-dependent ion channels.

PMID- 16989595
TI  - The potential impact of novel investigational compounds on human fertility.
AB  - There is considerable concern that the incidence of infertility in humans may be
      increasing, in some instances due to the action of bioactive xenobiotic compounds
      found in our environment; for example, high concentrations of xenobiotics with
      estrogenic activity can interfere with normal testicular function and fertility.
      However, recent studies have shown that very low concentrations of several
      estrogenic xenobiotics can have subtle, unexpected effects on sperm function.
      When tested in vitro, these compounds stimulate spermatozoa to become fertile
      very quickly, but continued stimulation causes them to burn out and lose
      fertilising ability; similar responses occurring in vivo could reduce fertility.
      In contrast, several other compounds, structurally related to amfetamine, have
      been shown to act on spermatozoa in vitro in a positive manner, stimulating cells
      to 'switch on' quickly and then preventing burnout so that they maintain
      fertilising potential; similar responses occurring in vivo could enhance
      fertility. These results could have implications for either reducing or enhancing
      natural fertility.

PMID- 16989596
TI  - Clinical trials of natural products as chemopreventive agents for prostate
      cancer.
AB  - Epidemiological research on prostate cancer risk in men throughout the world has
      identified significant correlations between dietary habits and prostate cancer
      occurrence. These studies served as a catalyst for exploration into the potential
      of dietary substances to act as chemopreventive agents against this disease, and
      include green tea catechins, lycopene, soy isoflavones, pomegranate phenolics,
      selenium, vitamins E and D, curcumin and resveratrol. Before these agents (in the
      dietary or purified forms) can be recommended as useful chemopreventive
      strategies for patients, their activity must be confirmed in rigorously designed
      clinical trials. This review discusses the preclinical and clinical data
      available for these dietary agents and describes relevant clinical trials
      currently being conducted.

PMID- 16989597
TI  - Investigating mammalian target of rapamycin inhibitors for their anticancer
      properties.
AB  - The mammalian target of rapamycin (mTOR) is a key element of the PI3KAkt (protein
      kinase B) signalling pathway, responsible for the regulation of cell growth and
      proliferation. There are two main downstream messengers of the mTOR kinase,
      eukaryotic initiation factor 4E-binding protein-1 and the 40S ribosomal protein
      S6 kinase 1, that control translation and cell-cycle progression. Abnormal
      activation of the mTOR pathway occurs frequently in numerous human malignancies;
      therefore, mTOR represents an attractive target for anticancer drug development.
      Rapamycin and its analogues CCI-779, RAD-001 and AP-23573 are known specific
      inhibitors of the mTOR kinase. Several clinical Phase I/II trials showed their
      activity in solid tumours and haematological malignancies. Moreover, inhibitors
      of mTOR were found to synergise with some cytostatics or other biological agents,
      which seems to be a promising direction for future strategies of antitumour
      treatment.

PMID- 16989598
TI  - Pharmacological management of SAPHO syndrome.
AB  - The SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome (SaS)
      includes different skeletal manifestations such as recurrent multifocal
      osteomyelitis, osteitis and arthritis, which are frequently associated with
      different forms of skin pustulosis (palmoplantar pustulosis, pustular psoriasis
      and severe acne). This syndrome is strictly related to the spondyloarthopathies
      (particularly to psoriatic arthritis) and many SaS cases fulfil the
      classification criteria for the spondyloarthopathies. Because SaS is an uncommon
      disease, current knowledge regarding its therapy is based on limited experiences
      gained by treating mainly small groups of patients. As a consequence, its
      treatment is still empiric. Several drugs (including NSAIDs, corticosteroids,
      sulfasalazine, methotrexate, ciclosporin, leflunomide, calcitonin and so on) have
      been administered and obtained conflicting results. The use of antibiotics, due
      to the isolation of Propionibacterium acnes from the bone biopsies of several
      subjects with SaS, has not represented a turning point in therapy, although some
      patients are responsive to this treatment. Initial reports concerning the
      administration of bisphosphonates (pamidronate and zoledronic acid) and of an
      anti-TNF-alpha agent (infliximab) are very promising for the future. In any case,
      larger, multi-centre, controlled, double-blind studies are required to emerge
      from the present pioneering phase.

PMID- 16989599
TI  - Integrin antagonists as therapeutics for inflammatory diseases.
AB  - Integrins are a family of heterodimeric cell surface receptors that mediate
      adhesion events crucial to cellular migration, proliferation and activation.
      Although critical to a normal immune response, integrins can also facilitate the
      progression of many inflammatory and autoimmune disorders. As such, they have
      attracted the attention of the pharmaceutical industry. Several humanised
      monoclonal antibodies directed against integrin targets have proven to be
      successful in clinical trials and have been approved for use in humans. This has
      not only resulted in effective therapies for patients, but also has provided
      important proof-of-concept studies for the development of small-molecule
      antagonists. This review focuses on those integrin subclasses that are being
      evaluated for their potential role in pulmonary, dermatological, gastrointestinal
      or rheumatic diseases. These include the alpha4 and beta2 integrins, as well as
      an emerging group of targets from the collagen-binding family of integrins.
      Interfering with integrin signalling pathways represents a future area of
      interest. The rationale for pursuing these targets, as well as the drugs
      presently under development, are discussed.

PMID- 16989600
TI  - Therapeutic potential of S179D prolactin--from prostate cancer to
      angioproliferative disorders: the first selective prolactin receptor modulator.
AB  - Increasing evidence suggests an important role for autocrine/paracrine prolactin
      in breast and prostate cancers and other disease states. Prolactin production in
      these extrapituitary sites is not governed by dopamine agonists, a finding that
      has spurred the production of prolactin receptor antagonists. This review focuses
      on one such antagonist, S179D prolactin, which was produced by mimicking a
      natural antagonist, phosphorylated prolactin. S179D prolactin is a very effective
      growth antagonist, partly because it inhibits signalling from unmodified
      prolactin and partly because it produces its own intracellular signal. This
      signal results in cell differentiation, cell-cycle arrest or apoptosis depending
      on dose, duration of treatment and cellular context. S179D prolactin is also a
      potent antiangiogenic and initial studies have shown it to be a potent anti
      inflammatory agent. In light of these additional modes of action, it is suggested
      that S179D prolactin should now be more aptly referred to as a selective
      prolactin receptor modulator.

PMID- 16989601
TI  - Aliskiren: a renin inhibitor offering a new approach for the treatment of
      hypertension.
AB  - In recent years, the renin-angiotensin-aldosterone system has been shown to be
      crucial not only in blood pressure haemostasis but also in the evolution of
      atherosclerosis, which ultimately determines morbidity and mortality. The
      angiotensin-converting enzyme inhibitors and, recently, the angiotensin receptor
      blockers (with their low adverse-effect profile) have added a new dimension to
      the drug treatment of hypertension. Just a decade after the introduction of
      angiotensin receptor blockers, physicians treating hypertension are now offered
      another exciting approach to achieving blockade of the renin-angiotensin
      aldosterone system through the inhibition of renin. This review outlines the
      background evidence for aliskiren, the first orally active renin inhibitor.

PMID- 16989602
TI  - Etanercept for refractory asthma therapy.
AB  - Asthma is a chronic disease of the airways in which inflammation causes bronchial
      hyper-reactivity and consequent asthma attacks triggered by various stimuli. The
      bronchospasm attacks are usually relieved by short-acting beta2 agonists, and
      inflammation and bronchial hyper-reactivity are reduced by maintenance therapy
      and, in particular, by inhaled corticosteroids. In milder asthma subjects, airway
      inflammation is dominated by eosinophils, whereas in more severe asthma increased
      neutrophil counts were detected. In severe/refractory asthma, TNF-alpha is known
      to play a role in the maintenance of neutrophilic inflammation and of bronchial
      hyper-responsiveness and is not influenced by corticosteroid therapy. Etanercept,
      a TNF-alpha-blocking agent, could represent one of the potential therapies for
      refractory asthma based on demonstrated safety and efficacy.

PMID- 16989603
TI  - 7th EFIS Tatra Immunology Conference. Molecular determinants of T-cell immunity.
      24-28 June 2006, High Tatra Mountains, Slovakia.
AB  - This meeting was hosted by the European Federation of Immunological Societies
      celebrating its 7th meeting in the High Tatra Mountains of Slovakia on 24-28 June
      2006. Entitled molecular determinants of T-cell immunity, the meeting covered a
      wide range of novel methods to regulate an unwanted immune response in
      autoimmunity and boost the immune system to combat viral infection and cancer.

PMID- 16989604
TI  - Hyperactive Himar1 transposase mediates transposition in cell culture and
      enhances gene expression in vivo.
AB  - The use of nonviral delivery systems results in transient gene expression, in
      part because of the low efficiency of DNA integration. Previously, vectors based
      on transposon systems such as Sleeping Beauty have been shown to be able to
      increase stable transfection efficiencies in cell culture and in animal models.
      Himar1, a reconstructed active transposon belonging to the Tc1/mariner
      superfamily, also has been used as a vector for stable gene delivery, but the
      rate of transposition after transfection is low. In this paper, we evaluate the
      potential of the hyperactive Himar1 transposase C9, in combination with the
      Himar1 inverted repeat transposon, as a gene delivery vector. The C9 transposase
      is a hyperactive mutant of Himar1 with two amino acid substitutions, Q131R and
      E137K, that result in an increase in activity relative to wild type. Here we
      demonstrate that cotransfection of the C9 transposase with a Himar1-based vector
      increases the frequency of stable gene expression in human cells in a transposase
      concentration-dependent manner. In addition, we establish that C9 transposase
      mediates integration of the transgene in mammalian cells at a frequency similar
      to that of Sleeping Beauty under some of the conditions tested. Last, we show
      significantly higher levels of reporter gene expression in vivo in mouse liver
      and in synovium of rabbit knee joints after injection of the transposon plasmid
      expressing the transgene and the C9 transposase. These data suggest that vectors
      based on the Himar1 transposable element, in conjunction with the hyperactive
      mutant transposase C9, may be suitable vectors for gene therapy applications.

PMID- 16989605
TI  - Impact of antiretroviral treatment-related toxicities on hospital admissions in
      HIV-infected patients.
AB  - While classical opportunistic infections have decreased as the main cause of
      hospital admission of HIV-infected patients, other conditions including drug
      related toxicities seem to have increased. We assessed the proportion of patients
      with hospital admission due to antiretroviral (ARV)-related toxicities over the
      last 7 years at a single HIV/AIDS reference institution located in Madrid. A
      total of 1981 consecutive hospital admissions in 1581 different HIV-infected
      patients were analyzed. Nearly half of them (45%) were on ARV therapy. Overall,
      ARV-related toxicities were the main or secondary reason for hospital admission
      in 141 patients (7%). Liver toxicity was the most frequent complication (n = 42;
      30%), of which one-third were associated with NVP use and 80% occurred in
      subjects with underlying chronic hepatitis C virus (HCV) infection. Other main
      ARV-related toxicities were bone marrow toxicity due to zidovudine (17%),
      pancreatitis (13%), and indinavirassociated nephrolithiasis (6%). Eight patients
      presented with symptomatic hyperlactatemia, two of them with lactic acidosis. All
      subjects with ARV-related toxicities had a favorable outcome, except one with
      prior HCVrelated end-stage liver disease, who died after experiencing hepatic
      decompensation following initiation of a protease inhibitor-based regimen.

PMID- 16989606
TI  - Association between physical and echographic fat thickness assessments and a
      lipodystrophy grading scale in lipodystrophic HIV patients: practical
      implications.
AB  - A simple diagnostic method for detecting in clinical routine HAART-associated
      lipodystrophy in HIV-infected patients is lacking. We studied the relationships
      between the scores obtained with a subjective lipodystrophy severity grading
      scale (LSGS) and standard anthropometric and echographic measurements of the
      subcutaneous and visceral fat thickness of 74 HIV-infected patients. Patients
      were divided into four groups according to their LSGS score (0, 1-7, 8-14, 15
      21). Significant correlations between the LSGS and the anthropometric and
      echographic measurements of fat thickness, mainly the limb circumferences
      (brachial: r= -0.43, p < 0.001; thigh: r= -0.41, p < 0.001), and, especially, the
      echographically assessed perirenal fat diameters either adjusted (r= 0.46, p <
      0.001) or nonadjusted to the body mass index (r= 0.35, p < 0.001) were observed.
      Significant differences in most of these anthropometric parameters between either
      the lowest (score 0) and the highest (score 15-21) score groups and the remaining
      groups were found, but not between the two intermediate groups (scores 1-7 vs. 8
      14). This suggests that lipodystrophy should be clinically categorized as absent,
      mild, or marked, and that even minor changes in physical aspect should be
      considered as indicative of this disorder. The combination of these subjective
      and objective parameters could be helpful in the early detection of lipodystrophy
      in clinical practice.

PMID- 16989607
TI  - Post-trial access to tested interventions: the views of IRB/REC chair,
      investigators, and research participants in a multinational HIV/AIDS study.
AB  - Controversy exists regarding an ethical requirement to make products proven
      effective in research available after the trial. Little is known about the views
      of several stakeholders. Phone or self-administered questionnaires were completed
      by 65 IRB/REC chairs, 117 investigators, and 500 research participants in a
      multinational HIV trial to assess their views about posttrial access to
      interventions proven effective in the study. A total of 83% of research
      participants, 29% of IRB/REC chairs, and 42% of researchers (p = 0.046) thought
      IL-2 should be guaranteed for every HIV-infected person in the world if proven
      effective. Most European and Latin American research participants thought IL-2
      should be provided free, while North American, Australian, and Thai participants
      commonly said at a price the average person could afford (p < 0.001). Most
      IRB/REC chairs and researchers thought the CIOMS "reasonable availability"
      requirement applied to people in the country where the study was conducted and
      meant a drug should be available at a price the average person could afford and
      that host country governments had primary responsibility for making it available.
      Most research participants believe an HIV drug proven effective in research
      should be made available to everyone in the world who needs it. IRB/REC chairs
      and researchers were less expansive both in who and how they thought a drug
      should be guaranteed.

PMID- 16989608
TI  - Virological outcome of chronic hepatitis B virus infection in HIV-coinfected
      patients receiving anti-HBV active antiretroviral therapy.
AB  - The immune suppression caused by HIV infection accelerates the course of liver
      disease caused by chronic hepatitis B virus (HBV) infection. We assessed the
      outcome of HIV/HBV-coinfected patients exposed to highly active antiretroviral
      therapy (HAART) including anti-HBV active drugs. Baseline and follow-up plasma
      HBVDNA and HIV-RNA levels, HBV serological markers, and CD4 counts were
      longitudinally evaluated in all HBsAg(+) individuals with HIV infection on
      regular follow-up at an urban HIV reference clinic. Out of 79 HBsAg(+) chronic
      carriers identified, 39 (50%) were HBeAg(+). Lamivudine (3TC) alone had been
      received by 37% of patients, while 3TC plus tenofovir (concomitantly or
      consecutively) had been taken by 58% of them. The median follow-up was of 52
      months. Loss of HBeAg or HBsAg occurred in 28% (10/36) and 13% (10/75) of
      patients, respectively. In multivariate analysis, only undetectable plasma HIV
      RNA levels [OR 4.58 (95% CI 1.25-16.78); p = 0.02] and greater CD4 gains on HAART
      [OR 1.003 (95% CI 1.000-1.006); p = 0.03] were associated with undetectable serum
      HBV-DNA at the end of follow-up. Anti-HBV active HAART makes it possible to
      achieve HBsAg clearance, anti-HBe seroconversion, and suppression of HBV
      replication in a substantial proportion of HBV/HIV-coinfected patients,
      particularly in those with complete HIV suppression and greater immune recovery.
      Thus, HBV/HIV-coinfected patients might benefit from an earlier introduction of
      HAART.

PMID- 16989609
TI  - Changes in blood cell membrane properties in HIV type-1-infected patients.
AB  - To evaluate the possible HIV-1 infection-induced changes in cell membrane
      properties and in calcium signaling, membrane fluidity, acetylcholinesterase
      (AChE, a glycosylphosphatidylinositol-anchored protein) activity, and
      intracellular calcium concentration ([Ca2(+)](int)) were evaluated in lymphocytes
      and erythrocytes of infected individuals, previous to their engagement in
      antiretroviral therapy. Membrane fluidity was assessed by fluorescence
      spectroscopy measurements, using the fluorescence probes 1,6-diphenyl-1,3,5
      hexatriene (DPH) and 1-[4-(trimethylamino)-phenyl]-6-phenyl-1,3,5-hexatriene (TMA
      DPH). AChE activity was determined by the colorimetric Ellman's method and
      [Ca2(+)](int) using the fluorescent fura-2 acetoxymethyl ester. When compared
      with the control group, lymphocytes of infected patients presented significantly
      decreased membrane fluidity, decreased AChE activity, and increased
      [Ca2(+)](int). Erythrocytes from HIV-infected patients presented decreased
      [Ca2(+)](int) when compared with the control group and decreased membrane
      fluidity near the lipid/water interface. Our data show that HIV-1 infection leads
      to biochemical and biophysical changes in the membrane itself and in membrane
      protein activity in lymphocytes (average of infected and noninfected
      subpopulations) and even in erythrocytes. The present observations are in
      agreement with a process of facilitated propagation of the infection to new
      cells, stimulation of virion production, and maintenance of a reservoir of
      erythrocyte-bound infectious virus.

PMID- 16989610
TI  - HIV type 1 inhibition by protein kinase C modulatory compounds.
AB  - The dichotomous effects of the protein kinase C (PKC) modulatory compounds 12
      myristate 13-acetate (PMA), prostratin, and ingenol 3-angelate (I3A) on HIV-1
      infection were investigated. PKC modulatory compounds were shown to be potent
      activators of cells latently infected with HIV-1 (I3A > prostratin). Conversely,
      PKC modulatory compounds inhibited infection of indicator cells (MAGI) with CXCR4
      tropic HIV-1 (PMA > I3A > prostratin), and I3A also inhibited infection with CCR5
      tropic virus (AD8-1). Pretreatment with the PKC inhibitors prior to treatment
      with either I3A or PMA resulted in increased infection, indicating inhibition is
      PKC mediated. Cell infections suggested that I3A rapidly inhibited the virus from
      infecting cells at an early point in infection. This observation was supported by
      the demonstration of inhibition at or before the synthesis of early reverse
      transcription products, and the inability of these compounds to block vesicular
      stomatitis virus (VSV) pseudotyped HIV-1 particles. As has already been shown
      with prostratin, treatment with I3A resulted in down-regulation of the CD4
      receptor and CXCR4 coreceptor suggesting that this was a contributor to the
      infection inhibition. Intriguingly, 48 h pretreatment of unstimulated peripheral
      blood mononuclear cells (PBMC) prior to infection resulted in abrogation of virus
      production at concentrations where receptor/ coreceptor levels were not
      significantly reduced. This result hints at the possibility of inhibition by a
      PKC modulatory compound of an early pathway of viral entry in PBMC.

PMID- 16989611
TI  - Efavirenz in plasma from HIV-infected patients does not directly block reverse
      transcriptase activity in cell-free assays but inhibits HIV replication in
      cellular assays.
AB  - The aim of this study was to characterize the potent nonimmunoglobulin (Ig)
      inhibitory activity defected in plasma from some HIV-infected, efavirenz (EFV)
      treated patients. Concentration of EFV in plasma was measured by HPLC and
      correlation with reverse transcriptase (RT) inhibition or decrease in virus
      replication in cellular assays was searched. After plasma protein elimination by
      ethanol extraction, an inhibitory activity is measurable on RT in vitro that
      correlates with EFV concentration determined by HPLC. However, total plasma
      containing EFV does not inhibit RT activity in cell-free assay, but it does
      efficiently inhibit virus replication in cell culture assays. Thus, despite being
      bound to plasma proteins (retention of EFV after extensive dialysis), EFV in
      plasma conserves its antiviral activity on infected cells. This observation
      precludes the use of crude sera and plasmas from EFV-treated patients for the
      study of antibody-mediated neutralizing activity.

PMID- 16989612
TI  - HIV type 1 zidovudine (ZDV) resistance in blood and uterine cervical secretions
      of pregnant women.
AB  - To determine if HIV-1 resistance testing of the blood predicts mutants in the
      genital secretions of ZDV-treated pregnant women, ZDV resistance mutations were
      assessed by an oligonucleotide ligation assay. ZDV resistance was detected in
      viral sequences from blood (16/48; 33%) and cervical secretions (6/24; 25%)
      collected during 57 pregnancies. The genotype of 11/69 (16%) resistance codons
      was discordant between blood and cervical virus of pregnant women near term.
      However, in only 1 (1.8%) of 57 pregnancies evaluated was resistant virus limited
      to the cervical secretions. ZDV-resistant virus is rarely limited to the female
      genital tract.

PMID- 16989613
TI  - A nonneutralizing anti-HIV Type 1 antibody turns into a broad neutralizing
      antibody when expressed on the surface of HIV type 1-susceptible cells. II.
      Inhibition of HIV type 1 captured and transferred by DC-SIGN.
AB  - Previously, we demonstrated that the expression of a nonneutralizing human anti
      HIV-1 gp41 scFv on the surface of HIV-1-susceptible cells markedly inhibits HIV-1
      replication and HIV-1 envelope-mediated cell-cell fusion. The inhibition is at
      the level of viral entry, specific for the HIV-1 envelope, and independent of
      virus tropism. In the previous studies, cell-free viruses of laboratory-adapted
      HIV-1 strains from subtype B were used to infect human CD4 T cell lines. To
      further test the effectiveness of this membrane-bound scFv (m-scFv) on HIV-1
      infection, in this study, we carried out experiments to determine whether the m
      scFv can neutralize infection of primary isolates from various HIV-1 subtypes and
      whether the m-scFv can neutralize HIV-1 captured and transferred by DC-SIGN on
      the surface of monocytic cell lines or DCs. We demonstrated that the m-scFv
      markedly inhibits primary isolates derived from various subtypes and
      significantly blocks HIV-1 captured and transferred by DC-SIGN on monocytic cell
      lines and on human DCs. Therefore, a nonneutralizing antibody acts as a broad
      neutralizing antibody when expressed on the cell surface, which significantly
      inhibits infection of both cell-free and DC-SIGN-captured and transferred virus.
      Our studies further point out the potential use of m-scFv as a inhibitor against
      HIV-1 transmission as well as a tool to dissect the mechanism of HIV-1 entry via
      DC-SIGN capture and transfer to CD4 T cells.

PMID- 16989614
TI  - Impact of Gag sequence variability on level, phenotype, and function of anti-HIV
      Gag-specific CD8(+) cytotoxic T lymphocytes in untreated chronically HIV-infected
      patients.
AB  - The role of cytotoxic T lymphocyte responses in controlling viral replication
      during chronic HIV infection remains controversial. Viral escape mutations driven
      by immune pressure have been postulated to be an important mechanism contributing
      to the evasion of CD8(+) T cell responses. To explore this issue in more detail,
      HIV-1 p17 sequence variability was examined in chronically HIV-infected patients,
      in parallel with the level, phenotype, and function of HIV-SL9-specific CD8(+) T
      cell. Thirty-one HLA-A*0201(+) (A2(+)) and 10 HLAA* 02() (A2()) patients were
      included. The phenotype of SL9-specific CD8(+) T cell and their ability to
      produce IFN-gamma were analyzed by multiparameter flow cytometry. The HIV Gag p17
      was sequenced and the mean variability score for each residue within SL9 and the
      two epitope flanking regions were calculated using Shannon entropy. The mean
      variability of SL9 and the proportion of patients with amino acid changes within
      SL9 were similar in A2(+) and A2() patients. Patients without Tet(+) cells had a
      significantly higher prevalence of aminoacid changes in SL9 than patients with
      Tet(+) cells. Interestingly, in patients with Tet(+) cells, the Y79F mutation
      within SL9 tended to be associated with lower levels of Tet(+) cells. We did not
      find any association between amino acid changes within SL9 and the
      differentiation stage of Tet(+) cells, or with IFN-gamma production. A similar
      analysis within the epitope flanking sequences did not reveal differences in the
      variability of these regions. These results suggest that viral mutations driven
      by immune selection pressure may play an important role in evading the
      immunological response in chronically HIV-infected individuals.

PMID- 16989615
TI  - Naive CD4(+) T cells and recent thymic emigrant levels in treated individuals
      with HIV: clinical relevance.
AB  - An increase in the levels of naive T cells after the administration of HAART is
      an indicator of the quality of immune reconstitution. We investigated whether
      levels of naive CD4 T cells (CD4(+)/CD45RA(+)) and of recent thymic emigrants
      (RTEs; CD4(+)/CD45RA(+)/CD31(+)) achieved in chronically treated HIV-infected
      patients could predict the length of time patients could interrupt antiretroviral
      treatment before their CD4 counts reached values < or =350 cells/mm(3) or HIV-1
      RNA levels increased to > or =100,000 copies/ml (Tibet cohort). Serial
      measurements revealed that the level of naive CD4 T cells among patients was
      extremely variable (5-95%), but the values for each patient remained stable
      throughout the study. We then focused on those patients who showed percentages of
      naive CD4 T cells above 60% or below 30%. The levels of naive T cells, RTEs,
      mononuclear cells containing T cell receptor excision circles (TRECs), and the
      strength of CD4 helper responses to HIV p24 antigen during treatment failed to
      predict the duration of treatment interruptions. In contrast, the median survival
      time of patients with a CD4 nadir > or =350 cells/mm(3) was 2-fold higher than
      that of patients with a CD4 nadir <350. However, the probability of restarting
      therapy in these two groups of patients was independent of the levels of naive T
      cells, RTEs, or TRECs.

PMID- 16989616
TI  - Ribonucleases in HIV type 1 inhibition: effect of recombinant RNases on infection
      of primary T cells and immune activation-induced RNase gene and protein
      expression.
AB  - Ribonucleases (RNases) have therapeutic potential against cancer and viral
      diseases and have been reported to inhibit replication of the human
      immunodeficiency virus type 1 (HIV-1) in chronically infected cell lines. The
      ribonuclease eosinophil-derived neurotoxin (EDN) is responsible for the anti-HIV
      1 activity of a soluble factor produced in response to human alloantigens (ASF).
      Four recombinant RNases (EDN; a four amino acid extension of the N-terminus EDN, 
      4EDN; RNase A; and angiogenin) were tested for inhibition of HIV-1 replication in
      PHA blasts. All RNases showed anti-HIV-1 activity, irrespective of whether the
      RNases were added before, during, or 2 h after infection. Polyclonal antibodies
      against the four RNases blocked the antiviral activity. ASF inhibited HIV-1
      replication in vitro if added up to 4 h after infection. We demonstrated that
      allostimulation induced EDN, RNase A, and angiogenin mRNA expression in
      peripheral blood mononuclear cells (PBMCs), although only EDN protein was
      detected. We identified monocytes and dendritic cells, but not macrophages or T
      cells, as EDN-producing cells. These findings raise the possibilities that
      multiple naturally occurring RNases may contribute to protection against HIV-1
      infection and could be considered for utilization in HIV-1 therapy.

PMID- 16989617
TI  - Antiretroviral therapy does not induce HIV type 1-specific neutralizing activity
      against autologous HIV type 1 isolates.
AB  - To determine the ability of antiretroviral treatment (ART) to deter viral
      replication in the long term, we tested autologous neutralization of HIV-1
      primary isolates in sera from six chronically HIV-1-infected patients before and
      during such treatment. For comparison, heterologous neutralization was tested in
      the same samples by using a panel of eight primary HIV-1 isolates. Preceding ART,
      none of the patients' samples contained neutralizing antibodies against
      autologous HIV-1 isolates. Subsequently, despite successful ART treatment during
      a 12- to 19-month period and a rise in CD4 T cell counts, the patients' viral
      neutralizing capacity did not increase significantly. Furthermore, the partial
      heterologous neutralizing response was not improved in these patients. This
      outcome signifies the failure of an HIV-1-specific humoral immune response to
      improve, despite successful ART. Therefore, our results emphasize the need for
      immunologic intervention before cessation of ART in chronically HIV-1-infected
      patients to achieve sustainable control of viral replication.

PMID- 16989618
TI  - A rapid and sensitive real-time PCR assay for the K65R drug resistance mutation
      in SIV reverse transcriptase.
AB  - Macaques infected with simian immunodeficiency virus (SIV) provide a suitable
      model for assessing the efficacy of antiretroviral (ARV) drug interventions and
      drug resistance selection associated with treatment. Resistance to the HIV
      reverse transcriptase inhibitor tenofovir continues to be examined in different
      treatment strategies in the macaque model. Evaluations of treatment interventions
      and drug resistance are hampered by the limited sensitivity of conventional
      population sequencing and the substantial effort involved in testing various
      tissue compartments in which viruses may reside. Therefore, a sensitive assay
      that permits simple and rapid testing for drug-resistant viruses would benefit
      appraisals of ARV treatments using in vivo models. To have this capability, we
      developed a real-time PCR-based assay for the detection of the SIV K65R reverse
      transcriptase mutation, a key marker for reduced susceptibility to tenofovir.
      Evaluations of SIV sequences yielded an assay detection limit mean of 0.4% mutant
      virus (range = 0.1-2%) in a wild-type background. In testing longitudinal plasma
      specimens from four SIV-infected macaques that received an active daily regimen
      of 30 mg/kg of tenofovir subcutaneously, the assay was able to detect K65R
      positive viruses in all animals within 1-7 weeks after treatment began. The
      emerging mutants were initially present at frequencies estimated between 0.4% and
      3%, below the detection capability of population sequencing. We propose the SIV
      K65R real-time PCR assay provides improved sensitivity and simplicity in studying
      tenofovir resistance in macaque models.

PMID- 16989619
TI  - Reverse transcriptase viral load correlates with RNA in SIV/SHIV-infected
      macaques.
AB  - Monitoring of viral load in macaques has usually been carried out using in-house
      PCR-based methods. A novel viral load (VL) kit (ExaVir Load) based on the
      measurement of lentivirus reverse transcriptase (RT) activity provides a
      potential alternative to methods that measure plasma viral RNA. RT is a
      fundamental and conserved activity of all retroviruses and the method should
      theoretically detect RT from all lentiviruses. To test this we compared VL
      measured by a commercially available RT kit with an in-house QC RT-PCR in
      macaques infected with SIV and SHIV. Both RT and RNA levels were measured over
      time in both sets of macaques. Results indicated that the relationship between
      both tests was strong for SIV and SHIV (r = 0.95 and r = 0.92, p < 0.0001,
      respectively). The VL trends also followed each other, indicating that both
      techniques measured the same process of viral replication. Furthermore, the RT
      load obtained using standardized control plasma samples supplied by NIBSC gave
      values close to the designated VL. However, when comparing RT load with QC RT-PCR
      a consistently three to five time higher level was obtained with the RT assay,
      highlighting potential differences in assay calibration. Even so, the data
      suggest that the RT assay is both sensitive and robust for use in the SIV/SHIV
      macaque model, particularly where molecular-based assays for SIV VL
      determinations are not easily available. The assay is also a commercially
      available kit and hence has the potential to reduce the variability seen between
      laboratories using in-house PCR.

PMID- 16989620
TI  - Antibody-dependent enhancement and vaccine development.

PMID- 16989623
TI  - Recombinant protective antigen 102 (rPA102): profile of a second-generation
      anthrax vaccine.
AB  - Recent terrorist attacks involving the use of Bacillus anthracis spores have
      stimulated interest in the development of new vaccines for anthrax prevention.
      Studies of the pathogenesis of anthrax and of the immune responses following
      infection and immunization underscore the pivotal role that antibodies to the
      protective antigen play in protection. The most promising vaccine candidates
      contain purified recombinant protective antigen. Clinical trials of one of these,
      recombinant protective antigen (rPA)102, are underway. Initial results suggest
      that rPA102 is well tolerated and immunogenic. Additional trials are necessary to
      identify optimal formulations and immunization regimens for pre- and postexposure
      prophylaxis. Future licensure of these and other candidate vaccines will depend
      on their safety and immunogenicity profiles in humans, and their ability to
      confer protection in animal models of inhalational anthrax.

PMID- 16989624
TI  - Prevention of shingles by varicella zoster virus vaccination.
AB  - Herpes zoster is caused by reactivation from previous varicella zoster virus
      (VZV) infection, and affects millions of people worldwide. It primarily affects
      older adults and those with immune system dysfunction, most likely as a result of
      reduced or lost VZV-specific cell-mediated immunity. Complications include post
      herpetic neuralgia, a potentially debilitating and chronic pain syndrome. Current
      treatment of herpes zoster and post-herpetic neuralgia involves antiviral agents
      and analgesics, and is associated with significant economic cost. Results from
      several clinical trials have determined that a live, attenuated VZV vaccine using
      the Oka/Merck strain (Zostavax) is safe, elevates VZV-specific cell-mediated
      immunity, and significantly reduces the incidence of herpes zoster and post
      herpetic neuralgia in people over 60 years of age. Regulatory approval has
      recently been obtained and once launched, it is expected that this vaccine will
      significantly reduce the morbidity and financial costs associated with herpes
      zoster. Durability of vaccine response and possible booster vaccination will
      still need to be determined.

PMID- 16989625
TI  - Experience with MCV-4, a meningococcal, diphtheria toxoid conjugate vaccine
      against serogroups A, C, Y and W-135.
AB  - Invasive disease due to Neisseria meningitidis continues to cause debility and
      death worldwide in otherwise healthy individuals. Disease epidemiology varies
      globally, but most cases are due to serogroups A, B, C, W-135 or Y. MenactraTM
      (MCV-4), a quadrivalent, meningococcal diphtheria-conjugate vaccine against
      serogroups A, C, Y, and W-135, was licensed in the USA for individuals 11-55
      years of age. Published results of clinical trials demonstrated robust immune
      responses that correlate with indicators of protection. MCV-4-induced antibody
      persist for up to 3 years after administration and anamnestic responses to
      revaccination. The vaccine was well tolerated; the most common reactions were
      transient, mild injection-site reactions and headache. MCV-4 should provide
      significant clinical benefits in the future.

PMID- 16989626
TI  - Are tick-borne encephalitis vaccines interchangeable?
AB  - Two tick-borne encephalitis vaccines produced by two vaccine manufacturers are
      available in most European countries. A question that is frequently asked
      regarding these two vaccines concerns their exchangeability, however, to date, no
      detailed assessment has been published. This review analyzes clinical studies
      investigating these two vaccines and describes possible approaches to boost or
      continue uncompleted primary immunization schedules, with either of the two tick
      borne encephalitis vaccines.

PMID- 16989627
TI  - Can leukemia-derived dendritic cells generate antileukemia immunity?
AB  - Tumor vaccines are being explored as a means of generating antitumor immune
      responses in patients with cancer. Based on the efficacy of allogeneic
      transplantation, acute myelogenous leukemia appears to be susceptible to cellular
      immune-based therapy. Dendritic cells (DCs) are the most potent antigen
      presenting cells and, as such, are being studied as a platform for the design of
      cancer vaccines. In acute leukemia, a promising approach involves the generation
      of DCs from leukemic blasts via cytokine exposure ex vivo. Leukemia-derived DCs
      potentially retain the tumor-associated antigens of the leukemic clone, which are
      presented in the context of the immune stimulating machinery of the mature DC.
      However, the efficacy of this approach may be limited by intrinsic abnormalities
      in the malignant clone that prevent differentiation towards a normal DC
      phenotype.

PMID- 16989628
TI  - Vaccination against malaria with live parasites.
AB  - Despite nearly 80 years of vaccine research and control efforts, malaria remains
      one of the most prevalent of all infectious diseases. The fact that people living
      in regions in which malaria is endemic eventually develop immunity to the
      parasite and the disease suggest that it might be possible to develop vaccines
      against malaria. Although few vaccination trials were conducted with whole
      parasites, the only protocol that leads to the induction of sterile immunity in
      humans relies on immunization with attenuated parasites. This observation has
      spurred the search for subunit vaccines that aim to reproduce this protection. As
      yet, none of the current candidate subunit vaccines have achieved complete
      protection reproducibly. This failure, coupled with the recent advent of the
      genetically modified Plasmodium parasites, has led to a renewed interest in the
      use of live parasites for vaccination. This article reviews past studies,
      summarizes recent developments in this field and discusses the challenges to be
      overcome before mass immunization with live parasites could be envisaged.

PMID- 16989629
TI  - Live attenuated oral cholera vaccines.
AB  - Live, orally administered, attenuated vaccine strains of Vibrio cholerae have
      many theoretical advantages over killed vaccines. A single oral inoculation could
      result in intestinal colonization and rapid immune responses, obviating the need
      for repetitive dosing. Live V. cholerae organisms can also respond to the
      intestinal environment and immunological exposure to in vivo expressed bacterial
      products, which could result in improved immunological protection against wild
      type V. cholerae infection. The concern remains that live oral cholera vaccines
      may be less effective among partially immune individuals in cholera endemic areas
      as pre-existing antibodies can inhibit live organisms and decrease colonization
      of the gut. A number of live oral cholera vaccines have been developed to protect
      against cholera caused by the classical and El Tor serotypes of V. cholerae O1,
      including CVD 103-HgR, Peru-15 and V. cholerae 638. A number of live oral cholera
      vaccines have also been similarly developed to protect against cholera caused by
      V. cholerae O139, including CVD 112 and Bengal-15. Live, orally administered,
      attenuated cholera vaccines are in various stages of development and evaluation.

PMID- 16989630
TI  - Suppressor of cytokine signaling 1 inhibition strategy to enhance anti-HIV
      vaccination.
AB  - Extensive efforts aimed at stimulating immune responses by modifying HIV antigens
      and using various delivery systems and adjuvants have so far failed to generate
      promising HIV vaccines, highlighting the urgent need to explore alternative
      immunization approaches. Antigen-presenting cells, such as dendritic cells, play
      a critical role in the initiation and maintenance of immune responses against HIV
      infection and dendritic cells are regulated by stimulatory, as well as inhibitory
      signaling. Recent studies demonstrate that the suppressor of cytokine signaling 1
      (SOCS1) functions as an antigen-presentation attenuator by restricting the Janus
      activated kinase-signal transducers and activators of transcription and Toll-like
      receptor-signaling pathways. SOCS1-silenced dendritic cells produce higher levels
      of both T-helper 1- and 2-polarizing cytokines, broadly enhance memory HIV
      specific B-cell and T-cell responses and activate natural killer cells owing to
      unbridled cytokine feedback signaling loops. Therefore, the inhibition of antigen
      presentation attenuators represents a generally applicable and alternative
      strategy for enhancing the potency of various forms of prophylactic and
      therapeutic HIV vaccines.

PMID- 16989631
TI  - Antigen-specific T-cell-mediated immunity after HIV-1 infection: implications for
      vaccine control of HIV development.
AB  - The definition of immune correlates of protection in HIV-1 infection is pivotal
      to the design of successful vaccine candidates and strategies. Although
      significant methodological and conceptual strides have been made in our
      understanding of HIV-specific cellular immunity, we have not yet defined those
      parameters that have a role in controlling the spread of HIV infection. This
      review discusses the basis of our understanding of HIV-specific cellular immunity
      and identifies its shortcomings. Furthermore, potential protective
      characteristics will be proposed that may ultimately be required for an effective
      vaccine designed to stimulate cellular immunity against HIV-1.

PMID- 16989632
TI  - Prospects for a vaccine against otitis media.
AB  - Otitis media is a major cause of morbidity in 80% of all children less than 3
      years of age and often goes undiagnosed in the general population. There is
      evidence to suggest that the incidence of otitis media is increasing. The major
      cause of otitis media is infection of the middle ear with microbes from the
      nasopharynx. The anatomical orientation of the eustachian tube, in association
      with a number of risk factors, predisposes infants and young children to the
      infection. Bacteria are responsible for approximately 70% of cases of acute
      otitis media, with Streptococcus pneumoniae, nontypeable Haemophilus influenzae
      and Moraxella catarrhalis predominating as the causative agents. The respiratory
      viruses, respiratory syncytial virus, rhinovirus, parainfluenza and influenza,
      account for 30% of acute otitis media cases. Over the past decade, there has been
      a profound increase in the reported resistance to antibiotics, which, with
      increased disease burden, has focussed attention on vaccine development for
      otitis media. A polymicrobial formulation containing antigens from all major
      pathogens would have the greatest potential to deliver a sustained reduction in
      the disease burden globally. The disappointing outcomes for otitis media seen
      with the polysaccharide pneumococcal conjugate vaccine have raised major
      challenges for the vaccination strategy. Clearly, more knowledge is required
      concerning immune mechanisms in the middle ear, as well as vaccine formulations
      containing antigens that are more representative of the polymicrobial nature of
      the disease. Antigens that have been extensively tested in animal models are now
      available for testing in human subjects.

PMID- 16989633
TI  - Investigating the association between influenza vaccination and reduced stroke
      risk.
AB  - Acute infections, mainly of the respiratory tract, have consistently been
      demonstrated to considerably increase the risk of stroke. At present, prospective
      interventional trials are lacking and there is no proof of the effectiveness of
      any therapeutic anti-infective strategy in stroke prevention. However, some new
      evidence from observational studies lends support to the idea that influenza
      vaccination may contribute importantly to fighting stroke. Although final proof
      of efficacy is still missing, patients with previous cerebral ischemia and
      subjects of any age at high risk of stroke should be encouraged to receive annual
      influenza vaccination.

PMID- 16989634
TI  - Listeria monocytogenes as a vector for tumor-associated antigens for cancer
      immunotherapy.
AB  - As a facultative intracellular bacterium, Listeria monocytogenes has adapted to
      live within the cytosol of the host cell. It is actively taken up by antigen
      presenting cells through phagocytosis, and as Listeria survive within these
      cells, it is an ideal vector for the delivery of antigens to be processed and
      presented through both the class I and II antigen-processing pathways. Once
      phagocytosed, Listeria produces virulence factors within the phagolysosome of the
      host cell, which allows it to break out of this organelle and live in the host
      cytosol. It is possible that these virulence factors can enhance the
      immunogenicity of tumor-associated antigens, which are poorly immunogenic. Recent
      progress in the development of this bacterium as a vaccine vector for tumor
      associated antigens is discussed in the context of bacterial vectors in general.
      In several mouse models, Listeria-based vaccines have been demonstrated to be an
      effective method of influencing tumor growth and eliciting potent antitumor
      immune responses. Safety issues and the transition of Listeria into human
      clinical trials will also be discussed in this review.

PMID- 16989635
TI  - Pneumococcal conjugate vaccines: emerging clinical information and its
      implications.
AB  - Since 2000, when the first pneumococcal conjugate vaccine was introduced into
      routine use in the USA, it has had a substantial impact on invasive pneumococcal
      disease both in the immunized and nonimmunized population. It has also been shown
      to reduce pneumonia and otitis in young children and has reduced antibiotic
      nonsusceptible pneumococcal infections. In the USA, three primary doses and a
      booster dose are recommended (a so-called '3 + 1 schedule'). Some countries have
      or will soon introduce routine immunization with fewer doses, with either two
      primary doses and a booster dose ('2 + 1 schedule') or no booster dose ('3 + 0
      schedule'). Some serotypes produce less antibody in a two-dose compared with a
      three-dose primary series. The booster dose may also be important in reducing
      nasopharyngeal carriage, hence absence of a booster dose may reduce indirect
      protection. It remains to be seen whether these schedule changes will reduce
      vaccine effectiveness within the population. Important future developments
      include extending the number of serotypes included in the vaccine and the
      possible extension of use into adults in whom indirect protection has been
      useful, but not as extensive as might be possible with direct immunization.

PMID- 16989636
TI  - The potential role of fowlpox virus in rational vaccine design.
AB  - The design of optimal vaccines requires detailed knowledge of how protective
      immune responses are generated in vivo under normal circumstances. This approach
      to vaccine development, where the immune correlates of protection are defined and
      vaccines are designed to elicit the same response, is called rational vaccine
      design. Poxviruses are attractive candidates for inclusion in such design
      strategies owing to their large genome, which allows for the inclusion of
      multiple heterologous genes, including those encoding antigens, co-stimulatory
      molecules and cytokines. Fowlpox virus, the prototypical member of the
      Avipoxvirus genus, is particularly suitable, as it is also incapable of
      replicating in mammalian cells. The potential of recombinant fowlpox virus as a
      safe vaccine vector is being evaluated currently in a number of clinical trials
      for diseases, including HIV, malaria and various types of cancer. Despite their
      promise, intricate details regarding how fowlpox virus interacts with the host
      immune system have not been resolved. In this review, the issues surrounding the
      use of fowlpox virus as a vaccine vector and possible strategies for enhancing
      its efficacy are discussed.

PMID- 16989638
TI  - Aiming to induce broadly reactive neutralizing antibody responses with HIV-1
      vaccine candidates.
AB  - Neutralizing antibody induction is a key feature of many effective vaccines and
      is the only immune response that has proven to be capable of completely blocking
      AIDS virus infection in animal models. Unfortunately, the extensive genetic
      variability and complex immune-evasion strategies of HIV-1 have thwarted all
      attempts to date at eliciting an effective neutralizing antibody response with
      candidate HIV-1 vaccine immunogens. Recent advances in our understanding of how
      these evasion strategies operate, coupled with growing progress in unravelling
      the structure and immunobiology of the viral envelope glycoproteins, are
      contributing to novel immunogen designs to overcome the many barriers to inducing
      protective antibodies against HIV-1.

PMID- 16989639
TI  - Kinetic diversity in G-protein-coupled receptor signalling.
AB  - The majority of intracellular signalling cascades in higher eukaryotes are
      initiated by GPCRs (G-protein-coupled receptors). Hundreds of GPCRs signal
      through a handful of trimeric G-proteins, raising the issue of signal
      specificity. In the present paper, we illustrate a simple kinetic model of G
      protein signalling. This model shows that stable production of significant
      amounts of free Galpha(GTP) (GTP-bound Galpha subunit) and betagamma is only one
      of multiple modes of behaviour of the G-protein system upon activation. Other
      modes, previously uncharacterized, are sustained production of betagamma without
      significant levels of Galpha(GTP) and transient production of Galpha(GTP) with
      sustained betagamma. The system can flip between different modes upon changes in
      conditions. This model demonstrates further that the negative feedback of
      receptor uncoupling or internalization, when combined with a positive feedback
      within the G-protein cycle, under a broad range of conditions results not in
      termination of the response but in relaxed oscillations in GPCR signalling. This
      variety of G-protein responses may serve to encode signal specificity in GPCR
      signal transduction.

PMID- 16989640
TI  - The Walker B motif of the second nucleotide-binding domain (NBD2) of CFTR plays a
      key role in ATPase activity by the NBD1-NBD2 heterodimer.
AB  - CFTR (cystic fibrosis transmembrane conductance regulator), a member of the ABC
      (ATP-binding cassette) superfamily of membrane proteins, possesses two NBDs
      (nucleotide-binding domains) in addition to two MSDs (membrane spanning domains)
      and the regulatory 'R' domain. The two NBDs of CFTR have been modelled as a
      heterodimer, stabilized by ATP binding at two sites in the NBD interface. It has
      been suggested that ATP hydrolysis occurs at only one of these sites as the
      putative catalytic base is only conserved in NBD2 of CFTR (Glu1371), but not in
      NBD1 where the corresponding residue is a serine, Ser573. Previously, we showed
      that fragments of CFTR corresponding to NBD1 and NBD2 can be purified and co
      reconstituted to form a heterodimer capable of ATPase activity. In the present
      study, we show that the two NBD fragments form a complex in vivo, supporting the
      utility of this model system to evaluate the role of Glu1371 in ATP binding and
      hydrolysis. The present studies revealed that a mutant NBD2 (E1371Q) retains wild
      type nucleotide binding affinity of NBD2. On the other hand, this substitution
      abolished the ATPase activity formed by the co-purified complex. Interestingly,
      introduction of a glutamate residue in place of the non-conserved Ser573 in NBD1
      did not confer additional ATPase activity by the heterodimer, implicating a vital
      role for multiple residues in formation of the catalytic site. These findings
      provide the first biochemical evidence suggesting that the Walker B residue:
      Glu1371, plays a primary role in the ATPase activity conferred by the NBD1-NBD2
      heterodimer.

PMID- 16989641
TI  - Activation of the ATF3 gene through a co-ordinated amino acid-sensing response
      programme that controls transcriptional regulation of responsive genes following
      amino acid limitation.
AB  - Expression of ATF3 (activating transcription factor 3) is induced by a variety of
      environmental stress conditions, including nutrient limitation. In the present
      study, we demonstrate that the increase in ATF3 mRNA content following amino acid
      limitation of human HepG2 hepatoma cells is dependent on transcriptional
      activation of the ATF3 gene, through a highly co-ordinated amino acid-responsive
      programme of transcription factor synthesis and action. Studies using transient
      over-expression and knockout fibroblasts showed that several ATF and C/EBP
      (CCAAT/enhancer-binding protein) family members contribute to ATF3 regulation.
      Promoter analysis showed that a C/EBP-ATF composite site at -23 to -15 bp
      relative to the transcription start site of the ATF3 gene functions as an AARE
      (amino acid response element). Chromatin immunoprecipitation demonstrated that
      amino acid limitation increased ATF4, ATF3, and C/EBPbeta binding to the ATF3
      promoter, but the kinetics of each was markedly different. Immediately following
      histidine removal, there was a rapid increase in histone H3 acetylation prior to
      an enhancement in ATF4 binding and in histone H4 acetylation. These latter
      changes closely paralleled the initial increase in RNA pol II (RNA polymerase II)
      binding to the promoter and in the transcription rate from the ATF3 gene. The
      increase in ATF3 and C/EBPbeta binding was considerably slower and more closely
      correlated with a decline in transcription rate. A comparison of the recruitment
      patterns between ATF and C/EBP transcription factors and RNA polymerase II at the
      AARE of several amino acid-responsive genes revealed that a highly co-ordinated
      response programme controls the transcriptional activation of these genes
      following amino acid limitation.

PMID- 16989642
TI  - Copper deprivation in rats induces islet hyperplasia and hepatic metaplasia in
      the pancreas.
AB  - BACKGROUND INFORMATION: Prolonged copper deprivation in rats followed by
      refeeding with a normal diet has previously been used to induce the appearance of
      hepatocyte-like cells in the pancreas, but the effects on islet size and
      morphology have not been determined. RESULTS: In the present study we
      investigated the distribution of pancreatic alpha- and beta-cells and of
      hepatocytes in adult rats fed a copper-deficient diet followed by refeeding with
      a normal diet. Immunohistochemical staining for insulin and glucagon showed that
      the islets of the copper-deficient group were up to 2.4 times larger in mass
      compared with controls. The islets were disorganized, with alpha-cells found in
      multiple layers at the periphery of the islet and sometimes deep in the core.
      Isolated alpha- and beta-cells were also found in increased numbers in the
      ductular system. Copper deprivation caused almost complete ablation of the acinar
      cells, and refeeding induced adipogenesis, acinar regeneration and hepatocyte
      like cells. Ductular proliferation and nerve hyperplasia were also present. The
      hepatocytes tended to be associated with islets or with ducts, rather than with
      residual pancreatic exocrine tissue. CONCLUSIONS: These data show that copper
      deficiency in rats, as well as inducing the appearance of hepatocytes, is capable
      of causing islet hyperplasia.

PMID- 16989643
TI  - Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and
      reduces myocardial necrosis in a model of acute myocardial infarction.
AB  - Therapies aimed at enhancing cardiomyocyte survival following myocardial injury
      are urgently required. As GHRP6 [GH (growth hormone)-releasing peptide 6] has
      been shown to stimulate GH secretion and has beneficial cardiovascular effects,
      the aim of the present study was to determine whether GHRP6 administration
      reduces myocardial infarct size following acute coronary occlusion in vivo.
      Female Cuban Creole pigs were anaesthetized, monitored and instrumented to ensure
      a complete sudden left circumflex artery occlusion for 1 h, followed by a 72 h
      reperfusion/survival period. Animals were screened clinically before surgery and
      assigned randomly to receive either GHRP6 (400 microg/kg of body weight) or
      normal saline. Hearts were processed, and the area at risk and the infarct size
      were determined. CK-MB (creatine kinase MB) and CRP (C-reactive protein) levels
      and pathological Q-wave-affected leads were analysed and compared. Evaluation of
      the myocardial effect of GHRP6 also included quantitative histopathology, local
      IGF-I (insulin-growth factor-I) expression and oxidative stress markers. GHRP6
      treatment did not have any influence on mortality during surgery associated with
      rhythm and conductance disturbances during ischaemia. Infarct mass and thickness
      were reduced by 78% and 50% respectively, by GHRP6 compared with saline (P<0.01).
      More than 50% of the GHRP6-treated pigs did not exhibit pathogological Q waves in
      any of the ECG leads. Quantitative histopathology and CK-MB and CRP serum levels
      confirmed the reduction in GHRP6-mediated necrosis (all P<0.05). Levels of
      oxidative stress markers suggested that GHRP6 prevented myocardial injury via a
      decrease in reactive oxygen species and by the preservation of antioxidant
      defence systems (all P<0.05). Myocardial IGF-I transcription was not amplified by
      GHRP6 treatment compared with the increase induced by the ischaemic episode in
      relation to expression in intact hearts (P<0.01). In conclusion, GHRP6 exhibits
      antioxidant effects which may partially contribute to reduce myocardial ischaemic
      damage.

PMID- 16989644
TI  - A variably spliced region in the type 1 ryanodine receptor may participate in an
      inter-domain interaction.
AB  - The aim of the present study was to examine residues that are variably spliced in
      the juvenile and adult isoforms of the skeletal-muscle RyR1 (type 1 ryanodine
      receptor). The juvenile ASI(-) splice variant is less active than the adult
      ASI(+) variant and is overexpressed in patients with DM (myotonic dystrophy)
      [Kimura, Nakamori, Lueck, Pouliquin, Aoike, Fujimura, Dirksen, Takahashi,
      Dulhunty and Sakoda (2005) Hum. Mol. Genet. 14, 2189-2200]. In the present study,
      we explore the ASI region using synthetic peptides corresponding to rabbit RyR1
      residues Thr3471-Gly3500 either containing [PASI(+)] or lacking [PASI(-)] the ASI
      residues. Both peptides increased [3H]ryanodine binding to rabbit RyR1s,
      increased Ca2+ release from sarcoplasmic reti-culum vesicles and increased single
      RyR1 channel activity. The peptide PASI(-) was more active in each case than
      PASI(+). [3H]Ryanodine binding to recombinant ASI(+)RyR1 or ASI(-)-RyR1 was
      enhanced more by PASI(-) than PASI(+), with the greatest increase seen when PASI(
      ) was added to ASI(-)RyR1. The activation of the RyR channels is consistent with
      the hypo-thesis that the peptides interrupt an inhibitory inter-domain inter
      action and that PASI(-) is more effective at interrupting this interaction than
      PASI(+). We therefore suggest that the ASI(-) sequence interacts more tightly
      than the ASI(+) sequence with its binding partner, so that the ASI(-)RyR1 is more
      strongly inhibited (less active) than the ASI(+)RyR1. Thus the affinity of the
      binding partners in this inter-domain interaction may deter-mine the activities
      of the mature and juvenile isoforms of RyR1 and the stronger inhibition in the
      juvenile isoform may contribute to the myopathy in DM.

PMID- 16989645
TI  - The Spn4 gene from Drosophila melanogaster is a multipurpose defence tool
      directed against proteases from three different peptidase families.
AB  - By alternative use of four RSL (reactive site loop) coding exon cassettes, the
      serpin (serine protease inhibitor) gene Spn4 from Drosophila melanogaster was
      proposed to enable the synthesis of multiple protease inhibitor isoforms, one of
      which has been shown to be a potent inhibitor of human furin. Here, we have
      investigated the inhibitory spectrum of all Spn4 RSL variants. The analyses
      indicate that the Spn4 gene encodes inhibitors that may inhibit serine proteases
      of the subtilase family (S8), the chymotrypsin family (S1), and the papain-like
      cysteine protease family (C1), most of them at high rates. Thus a cohort of
      different protease inhibitors is generated simply by grafting enzyme-adapted RSL
      sequences on to a single serpin scaffold, even though the target proteases
      contain different types and/or a varying order of catalytic residues and are
      descendents of different phylogenetic lineages. Since all of the Spn4 RSL
      isoforms are produced as intracellular residents and additionally as variants
      destined for export or associated with the secretory pathway, the Spn4 gene
      represents a versatile defence tool kit that may provide multiple antiproteolytic
      functions.

PMID- 16989647
TI  - Right meets left: a common mechanism underlying right and left ventricular
      outflow tract tachycardias.

PMID- 16989648
TI  - Dilated cardiomyopathy following right ventricular pacing for AV block in young
      patients: resolution after upgrading to biventricular pacing systems.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) has been demonstrated to
      result in clinical improvement in older adult patients with dilated
      cardiomyopathy (DCM), specifically those with left bundle branch block and
      prolonged QRS duration. We sought to demonstrate the benefits of CRT on
      improvement in cardiac function and clinical outcome in young patients that
      developed congestive heart failure (CHF) and DCM following cardiac pacing for AV
      block. METHODS AND RESULTS: We reviewed the charts of six patients who developed
      CHF or low cardiac output symptoms and DCM following implantation of right
      ventricular (RV)-based pacing systems for AV block, and subsequently underwent
      CRT. Patients ranged in age from 6 months to 23.7 years (mean: 11.3 +/- 3.6
      years). AV block was congenital (3), post-surgery (2), and acquired (1). Pacing
      had been performed for 0.1-14.5 (7.6 +/- 2.4) years prior to development of DCM.
      Two patients required listing for cardiac transplantation. Following CRT: (1) QRS
      duration shortened from 204 +/- 15 to 138 +/- 10 msec, P = 0.002, (2) left
      ventricular ejection fraction improved from 34 +/- 6 to 60 +/- 2%, P = 0.003, and
      (3) left ventricular end diastolic dimension shortened from 5.5 +/- 0.8 to 4.3 +/
      0.5 cm, P = 0.03. All patients demonstrated clinical improvement and have been
      weaned from CHF medications and listing for cardiac transplantation. CONCLUSIONS:
      CRT can benefit young patients that develop CHF and DCM following RV pacing for
      AV block. Upgrading to biventricular pacing systems should be considered early in
      the management of these patients prior to listing for cardiac transplantation.

PMID- 16989649
TI  - Long-term safety and efficacy of circumferential ablation with pulmonary vein
      isolation.
AB  - BACKGROUND: Each of the two main approaches to catheter ablation of atrial
      fibrillation (AF, segmental and circumferential) is associated with moderate long
      term efficacy. OBJECTIVE: To report the long-term outcomes of a modified
      technique that combines circumferential ablation with pulmonary vein (PV)
      isolation, determined by a circular mapping catheter and to determine the
      relationship between complete PV isolation and long-term efficacy. METHODS: The
      patient population was composed of 64 consecutive patients (47 men [73%]; age 59
      +/- 11 years) with AF who underwent catheter ablation. AF was paroxysmal in 29
      (45%) and nonparoxysmal in 35 (55%). Each patient was followed for a minimum of
      12 months. RESULTS: After a mean follow-up of 13 +/- 1 months, the long-term
      single-procedure success rate was 45% (n = 29) with an additional 4% (n = 3) of
      patients demonstrating improvement. With repeat procedures in 19 patients, the
      overall long-term success rate was 62% (n = 40) with 9% (n = 6) demonstrating
      improvement. All the patients who underwent repeat ablations had recovered PV
      conduction. Incomplete PV isolation was the only independent predictor of
      failure. A major complication occurred in four (6%) patients, including three
      patients with vascular complications and one with cardiac tamponade. CONCLUSION:
      Our results suggest that the long-term single-procedure efficacy of
      circumferential ablation with PV isolation in a cohort of patients with
      predominantly nonparoxysmal AF approaches 50%. Repeat procedures involving re
      isolation of the PVs result in a significant improvement in outcomes. Complete
      electrical isolation of the PVs has a significant impact on the long-term
      efficacy of the procedure.

PMID- 16989650
TI  - Fragmented, long-duration, low-amplitude electrograms characterize the origin of
      focal atrial tachycardia.
AB  - BACKGROUND: Focal atrial tachycardias (FAT) originate from areas with poor cell
      to-cell coupling. Due to cellular uncoupling extracellular potentials become
      fractionated. The degree of fragmentation may be used to identify the site of
      origin of FAT prior to catheter ablation. We studied electrical fragmentation in
      relation to the distance to the site of earliest activity during FAT. METHODS:
      Three-dimensional (3-D) electroanatomical activation/voltage maps obtained from
      patients (n = 15: 6 male, age 40 +/- 14 (19-72) years) referred for catheter
      ablation of FAT were analyzed. Bipolar atrial potentials (BP) were categorized
      according to the number of deflections. The peak-to-peak amplitude and the time
      interval between the first and last deflection (fractionation duration) of each
      BP were measured. RESULTS: Eighteen different atrial tachycardias (AT) (CL 346 +/
      109 [190-550]) msec were analyzed. The incidence of single potentials ranged
      from 30 to 81 (59 +/- 16)%. The occurrence of double and fractionated potentials
      < or = 2 cm of the site of earliest activity ("focal area") was higher compared
      to the remainder of the atria (67 +/- 22% vs 34 +/- 14%, P < 0.001). Focal area
      potentials were characterized by a longer duration (49 +/- 22 msec vs 34 +/- 17
      msec, P < 0.001) and a lower peak-to-peak amplitude (0.51 +/- 0.43 [0.12-1.7] mV
      vs 0.94 +/- 0.69 [0.22-2.58] mV, P = 0.03). Fractionation was not associated with
      FAT cycle length (r =-0.26, P = 0.29) or left atrial diameter (r = 0.47, P =
      0.30). CONCLUSION: Significant differences in fractionation, fractionation
      duration, and peak-to-peak-amplitude of atrial potentials between the focal area
      and the remainder of the atria exist. Fractionation and voltage mapping can be
      used, besides activation mapping, to identify the site of origin of FAT during
      catheter ablation.

PMID- 16989651
TI  - The impact of CT image integration into an electroanatomic mapping system on
      clinical outcomes of catheter ablation of atrial fibrillation.
AB  - BACKGROUND: A detailed appreciation of left atrial/pulmonary vein (LA/PV) anatomy
      may be important in improving the safety and success of catheter ablation (CA)
      for atrial fibrillation (AF). OBJECTIVES: The aim of this nonrandomized study was
      to determine the impact of computerized tomography (CT) image integration into a
      3-dimensional (3D) mapping system on the clinical outcome of patients undergoing
      CA for AF. METHODS: Ninety-four patients (age: 56 +/- 10 years) with AF
      (paroxysmal 46, persistent 48) underwent wide encirclement of ipsilateral PV
      pairs using irrigated radiofrequency ablation with the endpoint of electrical
      isolation. Ablation was guided by 3D mapping alone (electroanatomic 24,
      noncontact 23) in 47 (3DM group) patients and by CT image integration
      (Cartomerge) in 47 (CT group). In persistent AF, a combination of linear ablation
      and targeted ablation of complex fractionated electrograms was also performed.
      RESULTS: Successful PV electrical isolation did not differ between the two
      groups. A significant reduction in fluoroscopy times was demonstrated in the CT
      group (49 +/- 27 minutes vs 3DM group 62 +/- 26 minutes, P = 0.03). Arrhythmia
      recurrence was reduced in the CT group (32% vs 51% in the 3DM group, P < 0.01).
      In 30 symptomatic patients (12 CT and 18 3DM), repeat procedures for AF (13 in
      3DM and 5 CT, P < or = 0.10) and AT (5 in 3DM and 7 CT, P = NS) were performed.
      Overall success on 7-day monitor off antiarrhythmic drugs was achieved in 60% in
      the 3DM group when compared with 83% in the CT group (P < 0.05) at a follow-up of
      25 +/- 5 weeks. CONCLUSION: CA for AF guided by CT integration was associated
      with reduced fluoroscopy times, arrhythmia recurrence, and increased restoration
      of sinus rhythm. Improved visualization of complex LA geometries might improve
      the safety and success of CA for AF.

PMID- 16989652
TI  - Interactions between paced wavefronts and monomorphic ventricular tachycardia:
      implications for antitachycardia pacing.
AB  - OBJECTIVES: Interactions between paced wavefronts and monomorphic ventricular
      tachycardia (VT) dictate antitachycardia pacing outcomes. We used optical mapping
      to assess those interactions during single and dual site pacing of rabbit
      ventricular epicardium. METHODS AND RESULTS: Monomorphic VTs were initiated in
      six isolated rabbit hearts that were endocardially cryoablated to limit viable
      tissue to visible epicardium and establish apical tissue as the anatomic anchor.
      Preparations were optically mapped during single (n = 39) and dual (n = 43) site
      pacing at 50%-90% of VT cycle length (CL) with eight pulses per trial. Overall,
      we found six pulses that abruptly terminated VT. This occurred because the VT
      wavefront collided with the antidromic portion of the paced wavefront and the
      orthodromic portion of paced wavefront blocked in the VT's refractory region.
      When effective, dual site pacing that captured tissue at both leads
      simultaneously terminated the VT immediately, while single site pacing or dual
      site pacing that captured tissue at only one lead terminated the VT after
      resetting advanced the orthodromic wavefront. We found 12 pulses that induced
      polymorphic VT, with 11 of those pulses occurring during capture at only one
      lead. Expansion of the combined antidromic-VT wavefront around one or both ends
      of the arc of conduction block formed by the interaction of the orthodromic
      wavefront with the VT's refractory region initiated functional reentry. Six of
      these polymorphic VTs were nonsustained because the underlying wavefronts self
      terminated. The wavefronts did persist for 4.2 +/- 3.5 cycles before self
      terminating in these trials, and the post-pacing cycles presented a 146% increase
      in CL variability, compared with the variability prior to pacing. These temporal
      characteristics are similar to those of delayed termination in patients with
      ICDs. CONCLUSIONS: The main difference between pulses that terminated abruptly
      and pulses that induced polymorphic VT was the effective separation of the
      antidromic and orthodromic portions of the paced wavefront from one another.

PMID- 16989653
TI  - Wide complex beats with ventricular hypertrophy: what is the mechanism?

PMID- 16989654
TI  - Translation initiation and the fate of bacterial mRNAs.
AB  - Studies in pro- and eukaryotes have revealed that translation can determine the
      stability of a given messenger RNA. In bacteria, intrinsic mRNA signals can
      confer efficient ribosome binding, whereas translational feedback inhibition or
      environmental cues can interfere with this process. Such regulatory mechanisms
      are often controlled by RNA-binding proteins, small noncoding RNAs and structural
      rearrangements within the 5' untranslated region. Here, we review molecular
      events occurring in the 5' untranslated region of primarily Escherichia coli
      mRNAs with regard to their effects on mRNA stability.

PMID- 16989655
TI  - Nature of DNA-bound fatty acids in Pseudomonas aurantiaca.
AB  - The existence of Pseudomonas aurantiaca DNA-bound fatty acids and lipids is
      presented in this work. The isolation of DNA was carried out by two different
      procedures, namely, phenol and detergent-based phenol isolation in order to prove
      the presence of DNA-bound lipids. The lipid content of DNA is expressed in terms
      of fatty acid profile. A high level of 16:0, 18:0 and 18:1 is characteristic for
      tightly bound DNA lipids. On the other hand, the fatty acids such as 14:1,
      iso14:0 and iso16:0 are found in trace amounts only in DNA lipid fraction, but
      these fatty acids are not found in the whole-cell lipids. Absolutely no 3-hydroxy
      fatty acids were found in DNA lipids. However, both C16 and C18 species represent
      the main fatty acids of whole-cell and DNA-bound lipids. The presence of DNA
      bound lipids even under tough treatment of DNA allows to conclude that these
      lipids represent a special pool among cellular lipids.

PMID- 16989656
TI  - Identification and classification of genes required for tolerance to freeze-thaw
      stress revealed by genome-wide screening of Saccharomyces cerevisiae deletion
      strains.
AB  - Yeasts used in bread making are exposed to freeze-thaw stress during frozen-dough
      baking. To clarify the genes required for freeze-thaw tolerance, genome-wide
      screening was performed using the complete deletion strain collection of diploid
      Saccharomyces cerevisiae. The screening identified 58 gene deletions that
      conferred freeze-thaw sensitivity. These genes were then classified based on
      their cellular function and on the localization of their products. The results
      showed that the genes required for freeze-thaw tolerance were frequently involved
      in vacuole functions and cell wall biogenesis. The highest numbers of gene
      products were components of vacuolar H(+)-ATPase. Next, the cross-sensitivity of
      the freeze-thaw-sensitive mutants to oxidative stress and to cell wall stress was
      studied; both of these are environmental stresses closely related to freeze-thaw
      stress. The results showed that defects in the functions of vacuolar H(+)-ATPase
      conferred sensitivity to oxidative stress and to cell wall stress. In contrast,
      defects in gene products involved in cell wall assembly conferred sensitivity to
      cell wall stress but not to oxidative stress. Our results suggest the presence of
      at least two different mechanisms of freeze-thaw injury: oxidative stress
      generated during the freeze-thaw process, and defects in cell wall assembly.

PMID- 16989657
TI  - Carbon source utilization and accumulation of respiration-related substances by
      freshwater Thioploca species.
AB  - Carbon source utilization of Thioploca species from freshwater and brackish lakes
      in Japan was investigated. Microautoradiography demonstrated that freshwater and
      brackish Thioploca samples assimilate acetate. In addition, vertical nitrate
      transportation by freshwater Thioploca was examined by measuring substances
      accumulated in Thioploca filaments. The filaments of Thioploca sp. from Lake
      Biwa, a Japanese mesotrophic lake, contained nitrate at concentrations higher
      than ambient by two to three orders of magnitude. They also accumulated high
      concentrations of sulfate and abundant elemental sulfur. The results suggest that
      the Thioploca-specific strategy for sulfur oxidation, migration with accumulated
      nitrate, is effective even in freshwater habitats of lower sulfide supply.

PMID- 16989658
TI  - Novel uncultured Epsilonproteobacteria dominate a filamentous sulphur mat from
      the 13 degrees N hydrothermal vent field, East Pacific Rise.
AB  - Rapid growth of microbial sulphur mats have repeatedly been observed during
      oceanographic cruises to various deep-sea hydrothermal vent sites. The
      microorganisms involved in the mat formation have not been phylogenetically
      characterized, although the production of morphologically similar sulphur
      filaments by a Arcobacter strain coastal marine has been documented. An in situ
      collector deployed for 5 days at the 13 degrees N deep-sea hydrothermal vent site
      on the East Pacific Rise (EPR) was rapidly colonized by a filamentous microbial
      mat. Microscopic and chemical analyses revealed that the mat consisted of a
      network of microorganisms embedded in a mucous sulphur-rich matrix. Molecular
      surveys based on 16S rRNA gene and aclB genes placed all the environmental clone
      sequences within the Epsilonproteobacteria. Although few 16S rRNA gene sequences
      were affiliated with that of cultured organisms, the majority was related to
      uncultured representatives of the Arcobacter group (< or = 95% sequence
      similarity). A probe designed to target all of the identified lineages hybridized
      with more than 95% of the mat community. Simultaneous hybridizations with the
      latter probe and a probe specific to Arcobacter spp. confirmed the numerical
      dominance of Arcobacter-like bacteria. This study provides the first example of
      the prevalence and ecological significance of free-living Arcobacter at deep-sea
      hydrothermal vents.

PMID- 16989659
TI  - Common gene expression signatures in t(8;21)- and inv(16)-acute myeloid
      leukaemia.
AB  - Human acute myeloid leukaemia (AML) involving a core-binding factor (CBF)
      transcription factor is called CBF leukaemia. In these leukaemias, AML1 (RUNX1,
      PEBP2alphaB, CBFalpha2)-MTG8 (ETO) and CBFbeta (PEBP2beta)-MYH11 chimaeric
      proteins are generated by t(8;21) and inv(16) respectively. We analysed gene
      expression profiles of leukaemic cells by microarray, and selected genes whose
      expression appeared to be modulated in association with t(8;21) and inv(16). In a
      pair-wise comparison, 15% of t(8;21)-associated transcripts exhibited high or low
      expression in inv(16)-AML, and 26% of inv(16)-associated transcripts did so
      equivalently in t(8;21)-AML. These common elements in gene expression profiles
      between t(8;21)- and inv(16)-AML probably reflect the situation that AML1-MTG8
      and CBFbeta-MYH11 chimaeric proteins affect a common set of target genes in CBF
      leukaemic cells. On the other hand, 38% of t(8;21)-associated and 24% of inv(16)
      associated transcripts were regulated in t(8;21)- and inv(16)-specific manners.
      These distinct features of t(8;21)- and inv(16)-associated genes correlate with
      the bimodular structures of the chimaeric proteins (CBF-related AML1 and CBFbeta
      portions, and CBF-unrelated MTG8 and MYH11 portions).

PMID- 16989660
TI  - A detailed study of time-dependent changes in human red blood cells: from
      reticulocyte maturation to erythrocyte senescence.
AB  - The use of microfabrication technology in the study of biological systems
      continues to grow rapidly in both prevalence and ascendancy. Customised
      microdevices that provide superior results than traditional macroscopic methods
      can be designed in order to investigate specific cell types and cellular
      processes. This study showed the benefit of this approach in precisely
      characterising the progressive losses of surface area and haemoglobin (Hb)
      content by the human red blood cell (RBC), from newborn reticulocyte to senescent
      erythrocyte. The high-throughput, multiparametric measurements made on individual
      cells with a specialised microdevice enabled, for the first time, delineation and
      quantification of the losses that occur during the two stages of the human RBC
      lifespan. Data acquired on tens of thousands of red cells showed that nearly as
      much membrane area is lost during the 1-2 d of reticulocyte maturation (c. 10
      14%) as in the subsequent 4 months of erythrocyte ageing (c. 16-17%). The total
      decrease in Hb over the red cell lifespan is also estimated (c. 15%) and a model
      describing the complete time-course of diminishing mean RBC area and Hb is
      proposed. The relationship between the losses of Hb and area, and their possible
      influence on red cell lifespan, are discussed.

PMID- 16989661
TI  - Does the evidence about health risks associated with nitrate ingestion warrant an
      increase of the nitrate standard for drinking water?
AB  - Several authors have suggested that it is safe to raise the health standard for
      nitrate in drinking water, and save money on measures associated with nitrate
      pollution of drinking water resources. The major argument has been that the
      epidemiologic evidence for acute and chronic health effects related to drinking
      water nitrate at concentrations near the health standard is inconclusive. With
      respect to the chronic effects, the argument was motivated by the absence of
      evidence for adverse health effects related to ingestion of nitrate from dietary
      sources. An interdisciplinary discussion of these arguments led to three
      important observations. First, there have been only a few well-designed
      epidemiologic studies that evaluated ingestion of nitrate in drinking water and
      risk of specific cancers or adverse reproductive outcomes among potentially
      susceptible subgroups likely to have elevated endogenous nitrosation. Positive
      associations have been observed for some but not all health outcomes evaluated.
      Second, the epidemiologic studies of cancer do not support an association between
      ingestion of dietary nitrate (vegetables) and an increased risk of cancer,
      because intake of dietary nitrate is associated with intake of antioxidants and
      other beneficial phytochemicals. Third, 2-3 % of the population in Western Europe
      and the US could be exposed to nitrate levels in drinking water exceeding the WHO
      standard of 50 mg/l nitrate, particularly those living in rural areas. The health
      losses due to this exposure cannot be estimated. Therefore, we conclude that it
      is not possible to weigh the costs and benefits from changing the nitrate
      standard for drinking water and groundwater resources by considering the
      potential consequences for human health and by considering the potential savings
      due to reduced costs for nitrate removal and prevention of nitrate pollution.

PMID- 16989662
TI  - Brain-derived proteins in the CSF: do they correlate with brain pathology in CJD?
AB  - BACKGROUND: Brain derived proteins such as 14-3-3, neuron-specific enolase (NSE),
      S 100b, tau, phosphorylated tau and Abeta1-42 were found to be altered in the
      cerebrospinal fluid (CSF) in Creutzfeldt-Jakob disease (CJD) patients. The
      pathogenic mechanisms leading to these abnormalities are not known, but a
      relation to rapid neuronal damage is assumed. No systematic analysis on brain
      derived proteins in the CSF and neuropathological lesion profiles has been
      performed. METHODS: CSF protein levels of brain-derived proteins and the degree
      of spongiform changes, neuronal loss and gliosis in various brain areas were
      analyzed in 57 CJD patients. RESULTS: We observed three different patterns of CSF
      alteration associated with the degree of cortical and subcortical changes. NSE
      levels increased with lesion severity of subcortical areas. Tau and 14-3-3 levels
      increased with minor pathological changes, a negative correlation was observed
      with severity of cortical lesions. Levels of the physiological form of the prion
      protein (PrPc) and Abeta1-42 levels correlated negatively with cortical
      pathology, most clearly with temporal and occipital lesions. CONCLUSION: Our
      results indicate that the alteration of levels of brain-derived proteins in the
      CSF does not only reflect the degree of neuronal damage, but it is also modified
      by the localization on the brain pathology. Brain specific lesion patterns have
      to be considered when analyzing CSF neuronal proteins.

PMID- 16989663
TI  - The complete mitochondrial genome of a basal teleost, the Asian arowana
      (Scleropages formosus, Osteoglossidae).
AB  - BACKGROUND: Mitochondrial DNA-derived sequences have become popular markers for
      evolutionary studies, as their comparison may yield significant insights into the
      evolution of both the organisms and their genomes. From the more than 24,000
      teleost species, only 254 complete mtDNA sequences are available (GenBank status
      on 06 Sep 2006). In this paper, we report the complete mitochondrial genome
      sequence of Asian arowana, a basal bonytongue fish species, which belongs to the
      order of Osteoglossiformes. RESULTS: The complete mitochondrial genomic sequence
      (mtDNA) of Asian arowana (Scleropages formosus) was determined by using shotgun
      sequencing method. The length of Asian arowana mtDNA is ca. 16,650 bp (its
      variation is due to polymorphic repeats in the control region), containing 13
      protein-coding genes, 22 tRNA and 2 rRNA genes. Twelve of the thirteen protein
      coding genes were found to be encoded by the heavy strand in the order typically
      observed for vertebrate mitochondrial genomes, whereas only nad6 was located on
      the light strand. An interesting feature of Asian arowana mitogenome is that two
      different repeat arrays were identified in the control region: a 37 bp tandem
      repeat at the 5' end and an AT-type dinucleotide microsatellite at the 3' end.
      Both repeats show polymorphism among the six individuals tested; moreover the
      former one is present in the mitochondrial genomes of several other teleost
      groups. The TACAT motif described earlier only from mammals and lungfish was
      found in the tandem repeat of several osteoglossid and eel species. Phylogenetic
      analysis of fish species representing Actinopterygii and Sarcopterygii taxa has
      shown that the Asian arowana is located near the baseline of the teleost tree,
      confirming its status among the ancestral teleost lineages. CONCLUSION: The
      mitogenome of Asian arowana is very similar to the typical vertebrate
      mitochondrial genome in terms of gene arrangements, codon usage and base
      composition. However its control region contains two different types of repeat
      units at both ends, an interesting feature that to our knowledge has never been
      reported before for other vertebrate mitochondrial control regions. Phylogenetic
      analysis using the complete mtDNA sequence of Asian arowana confirmed that it
      belongs to an ancestral teleost lineage.

PMID- 16989664
TI  - Human fetal neuroblast and neuroblastoma transcriptome analysis confirms
      neuroblast origin and highlights neuroblastoma candidate genes.
AB  - BACKGROUND: Neuroblastoma tumor cells are assumed to originate from primitive
      neuroblasts giving rise to the sympathetic nervous system. Because these
      precursor cells are not detectable in postnatal life, their transcription profile
      has remained inaccessible for comparative data mining strategies in
      neuroblastoma. This study provides the first genome-wide mRNA expression profile
      of these human fetal sympathetic neuroblasts. To this purpose, small islets of
      normal neuroblasts were isolated by laser microdissection from human fetal
      adrenal glands. RESULTS: Expression of catecholamine metabolism genes, and
      neuronal and neuroendocrine markers in the neuroblasts indicated that the proper
      cells were microdissected. The similarities in expression profile between normal
      neuroblasts and malignant neuroblastomas provided strong evidence for the
      neuroblast origin hypothesis of neuroblastoma. Next, supervised feature selection
      was used to identify the genes that are differentially expressed in normal
      neuroblasts versus neuroblastoma tumors. This approach efficiently sifted out
      genes previously reported in neuroblastoma expression profiling studies; most
      importantly, it also highlighted a series of genes and pathways previously not
      mentioned in neuroblastoma biology but that were assumed to be involved in
      neuroblastoma pathogenesis. CONCLUSION: This unique dataset adds power to ongoing
      and future gene expression studies in neuroblastoma and will facilitate the
      identification of molecular targets for novel therapies. In addition, this
      neuroblast transcriptome resource could prove useful for the further study of
      human sympathoadrenal biogenesis.

PMID- 16989665
TI  - Chronic Granulomatous Disease; fundamental stages in our understanding of CGD.
AB  - It has been 50 years since chronic granulomatous disease was first reported as a
      disease which fatally affected the ability of children to survive infections.
      Various milestone discoveries from the insufficient ability of patients'
      leucocytes to destroy microbial particles to the underlying genetic
      predispositions through which the disease is inherited have had important
      consequences. Longterm antibiotic prophylaxis has helped to fight infections
      associated with chronic granulomatous disease while the steady progress in bone
      marrow transplantation and the prospect of gene therapy are hailed as long
      awaited permanent treatment options. This review unearths the important findings
      by scientists that have led to our current understanding of the disease.

PMID- 16989666
TI  - Regional differences in the pattern of airway remodeling following chronic
      allergen exposure in mice.
AB  - BACKGROUND: Airway remodeling present in the large airways in asthma or asthma
      models has been associated with airway dysfunction in humans and mice. It is not
      clear if airways distal to the large conducting airways have similar degrees of
      airway remodeling following chronic allergen exposure in mice. Our objective was
      to test the hypothesis that airway remodeling is heterogeneous by optimizing a
      morphometric technique for distal airways and applying this to mice following
      chronic exposure to allergen or saline. METHODS: In this study, BALB/c mice were
      chronically exposed to intranasal allergen or saline. Lung sections were stained
      for smooth muscle, collagen, and fibronectin content. Airway morphometric
      analysis of small (0-50000 microm2), medium (50000 microm2-175000 microm2) and
      large (>175000 microm2) airways was based on quantifying the area of positive
      stain in several defined sub-epithelial regions of interest. Optimization of this
      technique was based on calculating sample sizes required to detect differences
      between allergen and saline exposed animals. RESULTS: Following chronic allergen
      exposure BALB/c mice demonstrate sustained airway hyperresponsiveness. BALB/c
      mice demonstrate an allergen-induced increase in smooth muscle content throughout
      all generations of airways, whereas changes in subepithelial collagen and
      fibronectin content are absent from distal airways. CONCLUSION: We demonstrate
      for the first time, a systematic objective analysis of allergen induced airway
      remodeling throughout the tracheobronchial tree in mice. Following chronic
      allergen exposure, at the time of sustained airway dysfunction, BALB/c mice
      demonstrate regional differences in the pattern of remodeling. Therefore results
      obtained from limited regions of lung should not be considered representative of
      the entire airway tree.

PMID- 16989667
TI  - Prevention of boar taint in pig production. Abstracts of the 19th Symposium of
      the Nordic Committee for Veterinary Scientific Cooperation, Gardermoen, Norway,
      21-22 November 2005.

PMID- 16989668
TI  - Patience and change: a conflict of interests?

PMID- 16989669
TI  - Clinical review: alternative vascular access techniques for continuous
      hemofiltration.
AB  - Obtaining or maintaining vascular access for continuous hemofiltration can
      sometimes be problematic, especially in the child or adult in multiple organ
      failure with edema and/or coagulopathy. Problems commonly encountered include
      obstruction of the femoral vein by the catheter, insertion difficulties, safety
      concerns when cannulating the subclavian vein in coagulopathy, and catheter and
      circuit occlusion due to disseminated intravascular coagulation. For access in
      infants we describe a technique utilizing two single-lumen thin-walled vascular
      sheaths. For infants and small children initial access to the vein may be
      difficult due to edema or poor perfusion. For this situation we describe the
      'mini-introducer' technique of securing the vein and facilitating subsequent
      insertion of a relatively large guide wire. At any age an alternative route to
      the subclavian vein, from above the clavicle, is potentially 'compressible' in
      the event of hemorrhage during the procedure. We remind the reader of the utility
      of ultrasound guidance for cannulation of the internal jugular and subclavian
      veins. And lastly we review the options for venous return via the umbilical vein
      in infants, and via the antecubital vein in larger children and adults.

PMID- 16989670
TI  - The evidence base of telemedicine: Overview of the supplement.

PMID- 16989671
TI  - Diagnosis, access and outcomes: Update of a systematic review of telemedicine
      services.
AB  - Telemedicine services are being increasingly used. Although insurers and other
      payers are covering some services in the USA, the rationale for these coverage
      decisions is not always evidence-based. We reviewed the literature for
      telemedicine services that substitute for face-to-face medical diagnosis and
      treatment. We focused on three types of telemedicine services: store-and-forward,
      home-based and office/hospital-based services. Studies were included if they were
      relevant to at least one of the three study areas, addressed at least one key
      question and contained reported results. We excluded articles that did not study
      a service requiring face-to-face encounters (i.e. teleradiology was excluded).
      Our search initially identified 4083 citations. After review, 597 were judged to
      be potentially relevant at the title/abstract level. Following a full-text
      review, 106 studies were included. Store-and-forward services have been studied
      in many specialties, the most common being dermatology, wound care and
      ophthalmology. The evidence for their efficacy is mixed. Several limited studies
      showed the benefits of home-based telemedicine interventions in chronic diseases.
      Studies of office/hospital-based telemedicine suggest that telemedicine is most
      effective for verbal interactions, e.g. videoconferencing for diagnosis and
      treatment in specialties like neurology and psychiatry. There are still
      significant gaps in the evidence base between where telemedicine is used and
      where its use is supported by high-quality evidence. Further well-designed
      research is necessary to understand how best to deploy telemedicine services in
      health care.

PMID- 16989672
TI  - State Medicaid and private payer reimbursement for telemedicine: An overview.
AB  - Individual states in the USA were given the option of paying for telemedicine
      services with Medicaid (i.e. federal health-care funds administered by the state)
      in 1998, when the Health Care Financing Administration (HCFA) published final
      rules for Medicare payment for teleconsultations in health professional shortage
      areas (HPSAs). It was left to telemedicine practitioners in each state to
      negotiate the scope of the services covered with the state Medicaid office. Three
      reports of data gathered by 2002-03 surveys on state reimbursement policies have
      been reviewed, with additional information from a brief informal 2005 survey
      conducted by the author. In the seven years since 1998, 34 states have added
      coverage of telemedicine services to their Medicaid programmes, although there
      are wide variations in service coverage, payment policies, and geographical and
      other restrictions. There is less published information on private payer
      reimbursement. One survey performed by AMD Telemedicine (AMD) and the American
      Telemedicine Association (ATA) showed that over half of the 72 telemedicine
      programmes in 25 states delivering billable services were being reimbursed by
      private payers. In 1999, 43% of responding telemedicine networks saw
      reimbursement as a barrier to long-term sustainability, while in 2004 only 22%
      did so. It appears that some progress has been made in Medicaid and private payer
      reimbursement for telemedicine.

PMID- 16989673
TI  - What lessons can be learned from telemedicine programmes in other countries?
AB  - Reviews of telemedicine literature have shown that about half of the published
      studies come from the USA. This suggests that there is a large potentially useful
      stock of research outside the USA that could be used to guide telemedicine
      decision-making in the USA. In the present study, a request was sent to eight
      international experts in telemedicine asking about successful telemedicine
      programmes that have been assessed and could potentially be implemented in the US
      health-care system. We also conducted a focused review of a few key publications
      in the field to identify examples of successful telemedicine programmes. The
      review found that in some specific areas, such as teleradiology, telemental
      health, telegeriatric applications, e-referrals and discharge letters, and
      integration of health-care organizations with telemedicine networks, applications
      successfully implemented in international settings would be suitable for
      implementation in the USA. If telemedicine programmes from other countries are
      disseminated to the USA, differences in health-care systems, and technological
      infrastructure will probably affect their chances of success.

PMID- 16989674
TI  - The role of telemedicine in fostering health-care innovations to address problems
      of access, specialty shortages and changing patient care needs.
AB  - The integration of advanced technologies into health-care services promises to
      aid society in its transition to a coordinated, systems approach which is focused
      on disease prevention, enhanced wellness, chronic disease management, decision
      support, quality and patient safety. By incorporating such technologies,
      clinicians will be able to manage the growing volumes of medical information,
      research and decision support analytical tools. The deployment of advanced
      technologies will minimize the barriers of distance and geography to enhance
      access and facilitate the delivery of integrated health care. This will support
      and enhance the goals of the US federal Healthy People 2010 initiative.

PMID- 16989675
TI  - The diffusion of a medical innovation: where teleradiology is and where it is
      going.
AB  - Teleradiology is one of the more successful applications of telemedicine as
      measured by a bibliometric analysis of teleradiology research publications. The
      organizational diffusion of innovation framework is helpful in understanding the
      diffusion of teleradiology. Teleradiology had become part of the practices of two
      thirds of radiologists who responded to the American College of Radiology survey
      in 1999. It is clear that teleradiology has become routinized even though
      quantitative data are hard to find. Telecardiology may be the next successfully
      diffused form of telemedicine. The potential cloud on the horizon for
      telediagnostics is political pressure to avoid outsourcing to foreign countries,
      particularly those to which US information technology jobs have already been
      transferred. How the outsourcing issue is resolved will have a significant effect
      on teleradiology specifically, and, perhaps, telemedicine generally.

PMID- 16989676
TI  - Telehealth and the national health information technology strategic framework.
AB  - Telehealth has a role in the federally sponsored plan for health information
      technology (HIT) that encompasses electronic health records (EHRs) and the
      National Health Information Network (NHIN). The goals of telehealth and the
      national plan are complementary. One focuses on improving access to high quality
      health-care services and the other on the information systems to support those
      services. Telehealth needs the fully realized EHR to provide the best possible
      care when patients are geographically and chronologically separated from their
      providers. Some current telehealth projects are natural examples of how a
      distributed, accessible EHR such as that envisaged by the plan can be used to
      provide better care. The experiences of telehealth in organizing large networks
      of heterogeneous health-care entities can provide useful lessons as the process
      of implementing HIT moves forward.

PMID- 16989677
TI  - Will we see data repositories for telehealth activity in the near future?
AB  - Policy-makers and researchers lament the absence of telehealth registries to
      enhance knowledge regarding outcomes and efficacy of telehealth interventions. A
      number of different organizations operate registries, but there do not appear to
      be any true telehealth registries. One reason is that federal requirements
      through such policies as the Health Insurance Portability and Accountability Act
      (HIPAA) have led to heightened fear of inadvertently releasing confidential or
      unauthorized information. Also, it would be more efficient if patient data were
      captured electronically at the local level, ideally through electronic medical
      records (EMRs), and then transferred electronically to registries. However, the
      diffusion of EMRs at the local level is in its infancy. As a result, it is
      unlikely that we will see a comprehensive telehealth data repository within the
      next decade.

PMID- 16989678
TI  - Standards for data collection and monitoring in a telemedicine research network.
AB  - While a networked, nationwide health information system is financially and
      logistically impractical, the development of independent, regional systems is
      realistic and feasible. A Telemedicine Research Network (TRN) could connect a
      number of geographically disparate health systems. This would require the
      reconciliation of policies and practices in five principal areas: partner
      agreement on project scope; privacy, security and confidentiality; technical
      standards; telecommunications and computer infrastructure; change management and
      training. Initial establishment of a first-stage TRN would require very little
      technical development and would, instead, rely on trust among the partners. The
      development of standards-based TRNs will greatly increase the quality and
      quantity of telemedicine research.

PMID- 16989679
TI  - Alternatives to randomized controlled trials in telemedicine.
AB  - Research designs other than true experiments may be useful in the evaluation of
      telemedicine. Potential methods include those that do not rely on randomization
      and tight control of the intervention, and analysis of existing administrative
      and clinical databases. Quasi-experimental designs may also be useful, especially
      when conducted in association with careful statistical methods that allow the
      investigator to control for certain differences between groups. Databases, such
      as those maintained by the Centers for Medicare and Medicaid Services, contain
      information on both outcomes and claims, as well as disease/procedure registries
      and electronic health records. This may provide a potential tool for
      understanding the effects of telemedicine on access to care in conjunction with
      costs and quality. These different approaches have advantages and disadvantages,
      but may be useful in telemedicine, where the conduct of randomized controlled
      trials is generally very expensive and frequently not feasible.

PMID- 16989680
TI  - Health delivery system changes required when integrating telemedicine into
      existing treatment flows of information and patients.
AB  - Business model and financial recovery issues dominate discussions about using
      telemedicine to improve chronic disease management. The technical issues are
      numerous, daunting and complex, but many can be addressed using the resources and
      infrastructure available in large, well-integrated clinical information systems.
      The cost-benefit balance will change when it becomes possible to use devices that
      are owned by patients for everyday use, rather than installing special-purpose
      devices for telemedicine. Technology and communications capabilities are driven
      mainly by market factors other than uses for health care. Provider-side
      telemedicine capabilities, specifically for upload, storage and display of home
      medical data, will improve as technology develops. How health-care providers will
      process the larger amount of data made available by telemedicine is a clinical
      issue, but it is likely that software will emerge to assist in this task. The
      alignment of financial incentives for health-care providers is a decisive factor
      in understanding why telemedicine has had substantial deployment within the US
      Veterans Hospital Administration system, and to some extent within prison health
      systems and the Kaiser Permanente Health Plan, but much less widely in other
      settings.

PMID- 16989682
TI  - The effects of alpha1-acid glycoprotein on the reversal of chloroquine resistance
      in Plasmodium falciparum.
AB  - An in-vitro model based on the semi-automated microdilution technique has been
      developed for selecting compounds that might be used clinically for the reversal
      of chloroquine resistance. This was used initially to test the susceptibility of
      Plasmodium falciparum clone W2 to chloroquine (CQ). The model was then employed
      to investigate the effects of each of four resistance-reversing agents
      (verapamil, desipramine, chlorpheniramine and promethazine, at 1 microM) on this
      parasite's susceptibility to CQ, with and without alpha(1)-acid glycoprotein
      (AGP), at a patho-physiological concentration (1.25 g/litre), in the culture
      medium. In the absence of AGP, each of the resistance-reversing agents reduced
      the median inhibitory concentrations of CQ by 82%-97%, from a baseline value of
      about 94 ng/ml. In the presence of AGP, however, most of the resistance-reversing
      agents had much less effect. There appears to be competitive interaction between
      CQ, the resistance-reversing agents and AGP. The binding kinetics between CQ,
      resistance-reversing agents, AGP and other plasma proteins will clearly need to
      elucidated if clinically effective resistance-reversing agents are to be selected
      in vitro.

PMID- 16989683
TI  - Additive effects of ciprofloxacin on the in-vitro activity of chloroquine against
      a clinical isolate of Plasmodium falciparum.
AB  - As chloroquine and ciprofloxacin each possess substantial inhibitory activity
      against the schizonts of Plasmodium falciparum, it seems possible that a
      combination of the two drugs may be clinically useful. The effects on the
      erythrocytic stages of P. falciparum of combined treatment with chloroquine and
      ciprofloxacin were therefore evaluated in vitro, using the World Health
      Organization's standardized micro test. When used alone, the median inhibitory
      concentration (IC(50)) of chloroquine against the schizonts in the assay mixtures
      was found to be 7.75 microg/ml, whereas the corresponding value for ciprofloxacin
      was markedly lower, at 3.35 microg/ml. When they were used together, however,
      there was marked and statistically significant mutual enhancement of schizont
      inhibition by the two drugs, indicating that a chloroquine-ciprofloxacin
      combination may be useful clinically, in the treatment and management of P.
      falciparum malaria.

PMID- 16989681
TI  - Malaria and helminth interactions in humans: an epidemiological viewpoint.
AB  - In the tropics, helminths are among the most common chronic infections of humans
      and Plasmodium infections the most deadly. As these two groups of parasites have
      similar geographical distributions, co-infection is commonplace. It has
      increasingly been speculated that helminth infections may alter susceptibility to
      clinical malaria, and there is now increasing interest in investigating the
      consequences of co-infection, with studies yielding contrasting results. The
      immunological interactions between helminths and malarial parasites are unclear,
      although several hypotheses have been proposed. This review provides an
      epidemiological overview of the possible interactions between helminths and
      malarial parasites, in relation to geographical distributions and disease
      patterns, and provides a critical discussion of the results of the
      epidemiological studies that have so far been conducted to investigate the
      possible associations. Future studies that might be considered, in order to
      address the gaps in knowledge, are also considered.

PMID- 16989684
TI  - The in-vivo antimalarial activities of Uvaria chamae and Hippocratea africana.
AB  - The antimalarial activities of ethanolic root extracts of two plants used
      traditionally as malarial remedies in southern Nigeria, Uvaria chamae
      (Annonaceae) and Hippocratea africana (Hippocrateaceae), were studied in vivo, in
      mice infected with Plasmodium berghei berghei. The extract of U. chamae, when
      given orally at 300-900 mg/kg.day, exhibited significant antimalarial activity
      against both early and established infections. When established infections were
      treated, the mean survival time of the mice observed with this extract at 900
      mg/kg.day was similar to that seen with the positive control: chloroquine at 5
      mg/kg.day. The extract of H. africana, tested at oral doses of 200-600 mg/kg.day,
      also demonstrated promising blood schizontocidal activity, both in early and
      established infections. Although the question of their toxicities has still to be
      fully addressed, it is clear that both U. chamae and H. africana possess
      considerable antimalarial activity and they, or drugs based on their antimalarial
      constituents, may prove useful in the treatment of human malaria.

PMID- 16989685
TI  - Generic sodium stibogluconate is as safe and effective as branded meglumine
      antimoniate, for the treatment of tegumentary leishmaniasis in Isiboro Secure
      Park, Bolivia.
AB  - Human cutaneous leishmaniasis (CL) and mucous leishmaniasis (ML) are highly
      endemic in Isiboro Secure Park, which lies in the Bolivian department of
      Cochabamba--an area where branded meglumine antimoniate (Glucantime) is expensive
      and poorly distributed. The safety and efficacy of generic sodium stibogluconate
      (SSG), from Albert David Ltd, was therefore explored, in CL and ML cases from the
      park, who were treated with 20 mg/kg.day for 20 and 30 days, respectively. A
      questionnaire recording adverse effects was completed by a physician in each
      treatment centre. Efficacy of treatment was assessed at the end of treatment and
      at follow-ups 1 month and 3, 6 and 12 months later. Overall, 146 patients
      completed treatment with SSG in 2003-2004. No fatalities or severe adverse
      effects were reported but mild to moderate adverse effects were noted in 41 (28%)
      of the patients. The incidence of adverse effects was significantly higher among
      the cases of ML than among the cases of CL. Of the 86 patients with CL who
      completed 6 months of follow-up, 81 (94.2%) were considered to have been
      clinically cured; a comparable cohort of 69 CL cases who had been treated with
      Glucantime in 2001-2002 showed a similar frequency of clinical cure (90%).
      Generic SSG was shown to be safe and efficacious for the treatment of tegumentary
      leishmaniasis in Bolivia. Being several times cheaper than Glucantime, it could
      contribute to improving the access of CL and ML patients to treatment, not only
      in Bolivia but also in other countries of Latin America.

PMID- 16989686
TI  - Canine echinococcosis in Turkana (north-western Kenya): a coproantigen survey in
      the previous hydatid-control area and an analysis of risk factors.
AB  - A study of Echinococcus granulosus infection in dogs, with risk-factor analysis,
      was carried out in the endemic area of northern Turkana district, Kenya, using
      necropsy on 42 strays and a coproantigen-ELISA survey of 161 owned animals.
      During the post-mortem examinations, 14 (33%) of the necropsied dogs were found
      infected with E. granulosus, with a mean burden of 540 worms (range=two to 4080
      worms). The 26 necropsied dogs that came from the north-western Lokichoggio
      division--an area where, from 1983 to 1997, there had been a continuous programme
      of hydatid control--showed a similar prevalence of infection to the other dogs
      (34.6%) but a significantly lower mean burden, of 53 worms (range=two to 300).
      Forty-two (26%) of the animals tested for Echinococcus coproantigen were found
      positive. Although the dogs from the Lokichoggio division were more likely to be
      coproantigen-positive (29%) than those from the central Kakuma division (20%) or
      the north-eastern division (18%), the differences were not statistically
      significant. In questionnaire-based interviews, the owners of the dogs tested for
      coproantigens were asked about possible risk factors for canine infection with E.
      granulosus. Women were found to have twice the level of contact with dogs as men.
      The results of a univariate analysis of the dog-owners' responses revealed six
      factors that appeared to be significantly associated with a coproantigen-positive
      dog: non-restraint of the dog (P<0.001); dog fed on raw offal (P<0.001); the
      improper disposal of slaughter offal (P<0.001); the dog-owner's lack of knowledge
      about the transmission of echinococcosis (P=0.001); the dog not receiving
      anthelmintic treatment (P=0.003); and dog age < or =5 years (P=0.01). The results
      of a multivariate analysis confirmed that lack of dog restraint, access to raw
      offal, and young age of the dog (< or =5 years) each significantly increased the
      risk of coproantigen positivity (P, 0.005). Dogs that scavenged from cooking
      pots, were used to clean babies, had access to the inside of houses, and/or slept
      indoors appeared, however, to be at no increased risk of coproantigen positivity.
      The present results are discussed in relation both to older information on the
      epidemiology and role of human behaviour in the transmission of E. granulosus in
      Turkana, and the effects of the hydatid-control programme that ran continuously
      in the north-western division of Turkana between 1983 and 1997.

PMID- 16989687
TI  - Differential expression of collagen, MMP, TIMP and fibrogenic-cytokine genes in
      the granulomatous colon of Schistosoma mansoni-infected mice.
AB  - Schistosomiasis mansoni is a major helminthic disease of the tropics
      characterised by chronic hepatic and intestinal granulomatous inflammation and
      fibrosis. The fibrotic response is regulated by the amount of collagen deposited
      in the tissues and the degradation of that collagen by matrix metalloproteinases
      (MMP). In the murine model of the disease, although hepatic granuloma formation
      and the ensuing fibrosis have been thoroughly examined, there is a dearth of
      information on the intestinal fibrotic process. The expression of fibrosis
      related genes in the colons of chronically infected mice has therefore been
      investigated. Compared with that seen in uninfected mice, the expression of the
      genes coding for collagen of types I, III and IV was upregulated. Similarly, the
      messages for MMP-2, MMP-3 and MMP-8 were elevated, indicating the potential for
      collagen degradation. The genes for two tissue inhibitors of metalloproteinases
      (TIMP), TIMP-1 and TIMP-4, were, however, expressed at higher levels than those
      coding for the MMP. As a corollary, expression of the genes coding for three
      fibrogenic cytokines, transforming growth factor-beta, tumour necrosis factor and
      interleukin-4, was elevated. These data indicate that an imbalance in MMP:TIMP
      expression and enhanced levels of the messages for fibrogenic cytokines underlie
      the mechanism(s) of the colonic fibrosis seen in mice chronically infected with
      Schistosoma mansoni.

PMID- 16989688
TI  - Use of an inclusive-partnership strategy in urban areas of Orissa, India, to
      increase compliance in a mass drug administration for the control of lymphatic
      filariasis.
AB  - In India, the programme to eliminate lymphatic filariasis, which is largely based
      on mass administrations of diethylcarbamazine, has, in terms of coverage and
      compliance, been generally much less successful in urban areas than in rural
      communities. An innovative strategy to make the programme more effective in urban
      settings, largely based on an inclusive partnership and community participation,
      has recently been developed. An evaluation of the strategy's implementation in
      Orissa, which employed both quantitative and qualitative methods of data
      collection, revealed significantly higher coverage and compliance in an urban
      area where the strategy had been implemented than in a similar urban area where
      there had been no such intervention. Application of this strategy in other urban
      settings in general, and in small towns in particular, is recommended in India.

PMID- 16989690
TI  - Visceral leishmaniasis with duodenal involvement: three immunocompetent cases
      from southern Iran.

PMID- 16989689
TI  - Polymorphisms of the gene coding for copper/zinc superoxide dismutase (SOD1) in
      patients with Japanese encephalitis.
AB  - Japanese encephalitis is the commonest form of encephalitis globally. Most cases
      develop characteristic encephalitis but some also present with flaccid paralysis.
      The paralysis is secondary to damage at the alpha motor neurone, the site that is
      also damaged in amyotrophic lateral sclerosis (ALS). The gene coding for
      superoxide dismutase 1 (SOD1) is thought to be involved in ALS and may also be
      linked to susceptibility to Japanese encephalitis. To investigate this
      possibility, polymorphisms in the SOD1 gene were investigated, in 61 cases of
      Japanese encephalitis, 61 matched controls and 171 population controls, in
      Vietnam. Novel polymorphisms, found only in three of the cases and one of the
      population controls, may be involved with susceptibility to Japanese encephalitis
      and potentially to other flavivirus infections that lead to damage to the cells
      of the anterior horn. Further research on this possible association is required.

PMID- 16989692
TI  - Gene expression of leptin, resistin, and adiponectin in the white adipose tissue
      of obese patients with non-alcoholic fatty liver disease and insulin resistance.
AB  - BACKGROUND: Adipose tissue is an active endocrine organ that secretes a variety
      of metabolically important substances including adipokines. These factors affect
      insulin sensitivity and may represent a link between obesity, insulin resistance,
      type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study
      uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding
      adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal
      adipose tissue of morbidly obese patients undergoing bariatric surgery. METHODS:
      Morbidly obese patients undergoing bariatric surgery were studied. Patients were
      classified into two groups: Group A (with insulin resistance) (N=11; glucose
      149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B
      (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin
      3.431 +/- 1.162 microU/mL). RESULTS: Adiponectin mRNA in intra-abdominal adipose
      tissue and serum adiponectin levels were significantly lower in Group A compared
      to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin
      was higher in Group A than in Group B patients (P<0.005), resistin gene
      expression was not different between the two groups. Finally, for leptin, neither
      serum level nor gene expression was different between the two groups. Serum
      adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH)
      in this study (P=0.024). CONCLUSIONS: Obese patients with insulin resistance have
      decreased serum adiponectin and increased serum resistin. Additionally,
      adiponectin gene expression is also decreased in the adipose tissue of these
      patients. This low level of adiponectin expression may predispose patients to the
      progressive form of NAFLD or NASH.

PMID- 16989693
TI  - Massive localized lymphedema (MLL) in bariatric candidates.
AB  - BACKGROUND: Mild lymphedema of lower limbs and eventually abdomen is not
      exceedingly rare in morbid obesity. However, few large symptomatic masses have
      been reported. In a consecutive series of patients, all requiring resection of
      the lesion before bariatric treatment, clinical features and surgical findings
      are described, aiming to clarify the nature of this intricate problem. METHODS:
      Subjects (n=4, 50% females, age 34.0+/-13.7 years (19-53), BMI 56.4+/-10.5
      kg/m(2) (44.1-73.1) displayed lesions on the anteromedial aspect of the thigh
      (n=3) and hypogastrium (n=1). All reported episodes of intertrigo of local skin
      folds in the preceding years, managed by local care and antibiotics. The mass was
      described as a serious nuisance, impairing walking, dressing and personal
      hygiene. RESULTS: The mass was surgically removed without requirement for blood
      transfusion except in the case of one huge mass. Complications were relatively
      minor and consisted of partial skin dehiscence and lymph leakage for 2-3 weeks.
      Histologically, a complex pattern was observed including skin hypertrophy, edema,
      fibrosis, foci of microabscesses and dilated blood vessels, along with the
      pathognomonic lymphangiectasia. On follow-up to 6 months, improvement or
      restoration of the ability to walk occurred, with no additional skin infection
      and no recurrence. CONCLUSIONS: 1) Surgical treatment was effective. 2)
      Functional rehabilitation was achieved. 3) No recurrence was observed within the
      follow-up period.

PMID- 16989694
TI  - Dental complications following gastric restrictive bariatric surgery.
AB  - BACKGROUND: Morbid obesity is a scourge of the 21st century. The effective
      therapeutic measure is bariatric surgery. The medical literature has inadequately
      reported the potential deleterious effects of such surgery on dental health.
      Acidic levels in the oral cavity, which are known to be one of the postoperative
      side-effects of bariatric surgery, directly result in dental caries and tooth
      erosion. We investigated the self-assessment of postoperative bariatric patients
      with regard to their dental health and associated variables. METHODS: 113
      patients (25% compliance), who had been operated on in three Jerusalem hospitals,
      responded to a mailed questionnaire. RESULTS: Patients' average age was 40+/-10
      years; bariatric surgery had been performed 5+/-4 years previously. Of the
      patients, 37% reported eating more sweet foods after surgery, only 20% reported
      improved oral hygiene, only 34% reported increased frequency of visits to the
      dentist, and 37% reported greater dental hypersensitivity after surgery.
      Significant associations were found between reported dental hypersensitivity and
      vomiting (P=0.013), and also dental hypersensitivity and indigestion (P=0.021).
      Patients from the three hospitals reported different patterns of visits to the
      dentist. The most common variable (80% of the subjects) associated with visits to
      the dentist after surgery was dental hypersensitivity. CONCLUSION: Medical teams
      need to consider potential dental problems after bariatric surgery, and to supply
      their patients with the appropriate information and instructions regarding oral
      hygiene maintenance, healthy dietary patterns and regular dental health
      monitoring by a dentist or dental hygienist.

PMID- 16989695
TI  - Is bariatric surgery necessary after intragastric balloon treatment?
AB  - BACKGROUND: The use of the Bio-Enterics intra-gastric balloon (BIB) has been
      shown to be a safe and effective procedure for the temporary treatment of morbid
      obesity. We conducted a retrospective comparative analysis of the weight loss in
      patients that after BIB removal underwent bariatric surgery and those who did not
      wish surgery. METHODS: From January 2000 to March 2004, 182 BIBs were positioned
      in 175 patients (104 F / 71 M; mean age 37.1+/-11.6 years, range 16-67; mean BMI
      54.4 +/- 8.1 kg/m(2), range 39.8-79.5; mean %EW 160.8+/-32.9% range 89-264).
      Patients were excluded from this study who had emergency BIB removal for balloon
      rupture (n=2, 1.1%) and for psychological intolerance (n=7, 7.8%). All patients
      were scheduled for a bariatric operation, before BIB positioning. After BIB
      removal, a number of patients now declined surgery. Consequently, patients were
      allocated into 2 groups: Group A in whom BIB removal was followed by bariatric
      surgery (Lap-Band, laparoscopic gastric bypass, duodenal switch) (n=86); Group B
      patients who after BIB removal refused any surgical procedure (n=82). Both groups
      were followed for a minimum of 12 months. Results were reported as mean BMI and
      %EWL +/- SD. Statistical analysis was done by Student t-test or Fisher's exact
      test, with P<0.05 considered significant. RESULTS: Mean BMI and mean %EWL in the
      166 patients at time of removal were 47.3 +/- 8.1 kg/m(2) and 32.1+/-16.6%,
      respectively. At the same time, mean BMI was 47.6+/-6.9 and 48.1+/-6.5 kg/m(2) in
      group A and B (P=NS). At 12 months follow-up (100%), mean BMI was 35.1 kg/m(2) in
      Group A (BIB + surgery) and 51.7 kg/m(2) in Group B (BIB alone) (P<0.001).
      CONCLUSIONS: After BIB removal, half (49.4%) of the patients scheduled for
      surgery refused a bariatric operation. These patients returned to their mean
      initial weight at 12 months follow-up. Therefore, bariatric surgery after BIB
      removal is highly recommended.

PMID- 16989696
TI  - Effectiveness of laparoscopic sleeve gastrectomy (first stage of biliopancreatic
      diversion with duodenal switch) on co-morbidities in super-obese high-risk
      patients.
AB  - BACKGROUND: We evaluated laparoscopic sleeve gastrectomy (LSG) on major co
      morbidities (hypertension, type 2 diabetes / impaired glucose tolerance,
      obstructive sleep apnea syndrome (OSAS) and on American Society of
      Anesthesiologists (ASA) operative risk score in high-risk super-obese patients
      undergoing two-stage laparoscopic biliopancreatic diversion with duodenal switch
      (LBPD-DS). METHODS: 41 super-obese high-risk patients (mean BMI 57.3+/-6.5
      kg/m(2), age 44.6+/-9.7 years) were entered into a prospective study (BMI > or =
      60, or BMI > or = 50 with at least two severe co-morbidities, no Prader-Willi
      syndrome, no conversion, minimum follow-up 12 months). 9 patients had BMI > or =
      60. 17 patients (41.4%) had OSAS on C-PAP therapy. In 10 patients, at least one
      intragastric balloon had been positioned and 4 had undergone laparoscopic
      adjustable gastric banding, all with unsatisfactory results. At surgery, 41.5%
      were classified ASA 4 and 58.5% as ASA 3 (mean ASA score 3.4+/-0.5). Patients
      underwent evaluation every 3 months postoperatively and were restaged at 12
      months and/or before the second step. RESULTS: 60% of major co-morbidities were
      cured and 24% improved. Average BMI after 6 and 12 months was 44.5+/-8.1 and
      40.8+/-8.5 respectively (mean follow-up 22.2+/-7.1 months). After 12 months,
      57.8% of the patients were co-morbidity-free and 31.5% had only one major co
      morbid condition. At restaging, 20% of patients were still classified as ASA
      score 4 (OSAS on C-PAP therapy). 3 patients showed BMI <30 and were co-morbidity
      free 12 months after LSG. CONCLUSIONS: LSG represents a safe and effective
      procedure to achieve marked weight loss as well as significant reduction of major
      obesity-related co-morbidities. The procedure reduced the operative risk (ASA
      score) in super-obese patients undergoing two-stage LBPD-DS.

PMID- 16989697
TI  - Increased plasma levels of toxic pollutants accompanying weight loss induced by
      hypocaloric diet or by bariatric surgery.
AB  - BACKGROUND: Weight loss reduces the risk of several diseases. Increases of plasma
      organochlorine and pesticide compounds, however, have been observed with weight
      loss induced by a dietary intervention and by a gastroplasty. This increased
      concentration of toxic pollutants could be a side-effect of weight loss and a
      risk for health problems. The aim of this study was: 1) to observe if there is a
      relationship between the plasma concentration of organochlorines and BMI at
      steady state weight, and 2) to determine, after a bariatric surgical
      intervention, if the magnitude of the weight loss has a direct effect on this
      concentration. METHODS: Weight loss was obtained in obese individuals by a
      hypocaloric diet program until resistance and in morbidly obese individuals by a
      bariatric operation (biliopancreatic diversion - duodenal switch [BPD-DS]).
      Normal-weight individuals were tested to serve as controls. Blood samples were
      analyzed for organochlorine and pesticide compounds at baseline in all groups,
      after resistance to weight loss in obese individuals, and at 3 months and 1 year
      after surgery in morbidly obese individuals. RESULTS: At steady state weight,
      organochlorine and pesticide compounds were found in all groups, and the sum of
      all organochlorine compounds correlated with age and not BMI. Weight loss
      averaged 12.1% of the initial body weight after dieting and 20.9% at 3 months
      after surgery, respectively. This weight loss yielded significant increases in
      total plasma organochlorine concentration (increase of 23.8% for obese and 51.8%
      for morbidly obese individuals). For morbidly obese individuals, the weight loss
      at 1 year after surgery (46.3%) yielded a 388.2% increase in total plasma
      organochlorine concentration. CONCLUSION: Plasma organochlorine concentration
      increases with weight loss and is related to the magnitude. Future research will
      have to determine if: 1) this pollutant concentration remains elevated over time
      and 2) there are long-term effects of this high concentration on health.

PMID- 16989698
TI  - Histologic study of tissue reaction to the gastric band: does it contribute to
      the problem of band erosion?
AB  - BACKGROUND: One of the major complications of gastric banding is intragastric
      migration of the band. The frequency ranges from 0.5% to 3.8%, and removal of the
      band is always required. We undertook a prospective study with the aim to
      determine the reasons for this significant complication in bariatric surgery.
      METHODS: 480 morbidly obese patients underwent adjustable gastric banding in our
      Surgical Department, from February 1998 to October 2005. 31 of them were
      reoperated for different surgical problems, at an average time of 39 months after
      the bariatric procedure. During the reoperation, some fragments of fibro-adipose
      tissue in close contact with the band were removed. They were examined, focusing
      on the following parameters: acute and chronic inflammation, fibrosclerosis, and
      foreign body granulomatous reaction. RESULTS: Histological assessment showed the
      presence of acute and chronic inflammation, generally of mild and medium grade;
      fibrosclerosis was present mostly in a severe form, indicating a biological
      periprosthesic wall that separates and protects the gastric wall from the band;
      no cases of foreign body reaction were observed, nor were silicone inclusions
      found inside the inflammatory cells. CONCLUSION: The histologic changes of
      periprosthesic tissue do not appear to account for endoluminal migration of the
      gastric band. Thus, band erosion could have a closer correlation with other
      causes, such as infection of the band or intraoperative surgical damage, possibly
      due to direct mechanical action or to the thermal effect of the electric scalpel.

PMID- 16989699
TI  - Intragastric stimulation is ineffective after failed adjustable gastric banding.
AB  - BACKGROUND: Gastric pacing has gained popularity as an effective and safe
      minimally invasive procedure to treat morbid obesity. This study evaluates the
      outcome of gastric pacing as a bariatric re-do procedure in patients who
      developed failure after adjustable gastric banding (AGB) due to band migration.
      METHODS: 8 patients were enrolled in this analysis. After implantation of an AGB,
      they had developed band failure due to band migration. The implantable gastric
      stimulator (IGS) was implanted laparoscopically as a second-line operation after
      gastroscopic removal of the band. RESULTS: Median time (range) from AGB
      complication to implantation of the IGS was 42 (10.3-50.3) months. During that
      time, all 8 patients had regained significant weight. All IGS devices could be
      implanted laparoscopically, without intra- or perioperative complications. The
      minimal body weight following IGS implantation was reached after 5 (0-12) months.
      The median observation time was 23 (11.3-27.5) months. 1 year after IGS
      implantation (n=7), median weight was 116 (98-165) kg, equivalent to a median BMI
      of 41.1 (36.055.8) kg/m(2), which is not statistically different to preoperative
      values and therefore prompted us to stop our ongoing trial. In all but 2
      patients, the IGS device was explanted. During the same procedure, patients
      underwent a gastric sleeve resection (n=4) or a Roux-en-Y gastric bypass (n=2).
      CONCLUSION: The implantation of an IGS was an ineffective second-line operation
      after AGB migration.

PMID- 16989700
TI  - Avoiding complications after laparoscopic esophago-gastric banding: experience
      with 400 consecutive patients.
AB  - BACKGROUND: Among bariatric operations, laparoscopic adjustable gastric banding
      (LAGB) has been the preferred one in Europe and Australia, and has become
      recently popular in the USA. Like every surgical procedure, however, it is not
      devoid of specific complications, like slippage, band erosion, outlet obstruction
      and port problems. Assuming that the absence of the pouch may avoid postoperative
      slippage, we introduced the technique of esophago-gastric placement, instead of
      the original gastric banding technique. A further technical variant, introduced
      in June 2002, consists of suturing the gastric fundus to the left hemidiaphragm,
      using two non-resorbable sutures and pledgets. METHODS: Between January 1999 and
      July 2005, 400 LAGBs have been placed in 90 males and 310 females, with the
      technical variants above. Mean age was 42 (range 17-69 years), and mean BMI was
      44.8 kg/m(2) (range 33-67). RESULTS: Mean hospital stay was 2.5 days (range 1
      17). Mortality has been zero. Major complications included: 16 slippages (after a
      range of 6-45 months), 5 outlet obstructions (immediately after the operation),
      and one intragastric migration (after 2 years). Minor complications included 18
      port problems. Since the introduction of gastric fundus fixation to the diaphragm
      in 2002, gastric slippage has decreased from 8% to 0.9%. BMI has decreased from
      44.8 to 32 kg/m(2) at 60 months. CONCLUSIONS: The technique herein presented is
      effective and useful to prevent postoperative gastric slippage. It does not
      induce pseudo-achalasia, if strictly controlled. In fact, it is avoided by the
      patient due to the immediate appearance of dysphagia, in the case of wrong food
      ingestion. Long-term clinico-radiological follow-up confirms that the technique
      is safe and effective in motivated patients with good compliance and willing to
      undergo periodic studies.

PMID- 16989701
TI  - Hepatic outcomes after jejunoileal bypass: is there a publication bias?
AB  - BACKGROUND: One of the reasons why jejunoileal bypass (JIB) was abandoned were
      reports of liver failure. The aim of this study was to describe histological
      findings in the intraoperative and follow-up liver biopsies of a cohort of super
      obese patients who had undergone JIB. METHODS: 50 consecutive patients underwent
      JIB. Samples of liver biopsies performed intraoperatively (41 patients) and in
      the follow-up (31 patients) were evaluated. Brunt's scale was used. RESULTS: Mean
      age at operation was 37.9 +/- 7.6 years, and 15 patients (30.6%) had diabetes
      type 2, 20 (40.8%) had dyslipidemia, 29 (59.2%) had high blood pressure, and one
      (0.5%) had hepatitis C. Mean BMI preoperatively was 52.8 +/- 7.5 kg/m(2). Mean
      follow-up time was 67.0 +/- 42.8 months. At the time of the latest liver biopsy,
      the mean BMI was 35.7 +/- 7.5 kg/m(2). The % excess weight loss (%EWL) was 62.4
      +/- 20.0%. 8 deaths (16%) have occurred, none from liver-related complications.
      At liver biopsy during the JIB operation, NAFLD was confirmed in 36 patients
      (86.7%) and NASH in 13 (31.7%). In 25 patients with mean follow-up of 4.8 +/- 4.0
      years, there was no statistically significant change in the liver histology
      regarding the extent of steatosis (P=0.20), steatohepatitis (P=0.74) and fibrosis
      (P=0.71). CONCLUSIONS: There was a significant metabolic improvement, maintenance
      of the %EWL, and no worsening of liver histology. There has possibly been a
      publication bias concerning liver outcomes, where the type of JIB and the
      concomitance of hepatitis C were not taken into account.

PMID- 16989702
TI  - Morbidly obese individuals with impaired fasting glucose have a specific pattern
      of insulin secretion and sensitivity: effect of weight loss after bariatric
      surgery.
AB  - BACKGROUND: Obesity is often associated with hyper-secrection of insulin.
      Impaired fasting glucose (IFG) has recently been redefined as a fasting plasma
      glucose of 5.6-6.9 mmol/L. The aim of this study was to determine whether changes
      in insulin secretion in morbidly obese persons also commence with normal serum
      glucose levels. METHODS: 32 morbidly obese subjects were studied before and after
      bariatric surgery. Measurements were made of glucose tolerance (K(G)), insulin
      sensitivity (SI), first-phase insulin release and the disposition index (DI) from
      a frequently sampled intravenous glucose tolerance test. RESULT: In morbidly
      obese subjects, the SI (P<0.01), DI (P<0.01) and first-phase insulin release
      (P<0.02) started changing with serum glucose levels considered to be normal (5.00
      5.28 mmol/L). K(G) showed a clear slope according to the baseline glycemia status
      (P<0.05), and it was significantly related with the DI, both before (r=0.76,
      P<0.001) and after (r=0.57, P=0.002) surgery. Following surgery, all the
      variables significantly associated with insulin secretion and insulin sensitivity
      recovered significantly. The most significant changes occurred in morbidly obese
      individuals with IFG. CONCLUSIONS: Morbidly obese subjects show slopes of insulin
      sensitivity and insulin secretion in accordance with their baseline serum glucose
      levels. The fall in first-phase insulin release begins when serum glucose values
      are considered normal. Morbidly obese persons with the IFG phenotype have a
      specific pattern of insulin sensitivity and insulin secretion. K(G) clearly
      discriminates the clinical phenotypes, depending on baseline serum glucose
      levels.

PMID- 16989703
TI  - Short-term changes in insulin resistance following weight loss surgery for morbid
      obesity: laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux
      en-Y gastric bypass (LRYGBP) both effectively treat the insulin resistance
      associated with type 2 diabetes mellitus (T2DM). Restriction of caloric
      consumption, alterations in the entero-insular axis or weight loss may contribute
      to lowering insulin resistance after these procedures. The relative importance of
      these mechanisms, however, following LAGB and LRYGBP remain unclear. The aim of
      this study was to compare directly the short-term changes in insulin resistance
      following LAGB and LRYGBP in similar populations of patients. METHODS: Patient
      preference determined operation type. The Homeostasis Model Assessment for
      Insulin Resistance (HOMA IR) was used to measure insulin resistance. Preoperative
      values were compared to postoperative levels obtained within 90 days of surgery.
      Significant differences between groups were tested by ANOVA. RESULTS: There were
      no significant preoperative differences between groups. The 56 LAGB patients had
      a mean age of 42.5 years (25.7-63), BMI of 45.5 kg/m(2) (35-66) and preoperative
      HOMA IR of 4.1 (1.4-39.2). 75% of LAGB patients were female and 43% had T2DM. The
      61 LRYGBP patients had a median age of 39.9 years (22.1-64.3), BMI of 45.0
      kg/m(2) (36-62), and preoperative HOMA IR of 5.0 (0.6-56.5). 79% of LRYGBP
      patients were women and 44.3% had T2DM. Median follow-up for LAGB patients was 45
      days (18-90) and for LRYGBP patients 46 days (8-88 days). LAGB patients had a
      median of 14.8% excess weight loss (6.9%-37.0%) and LRYGB patients 24.2% (9.8%
      51.4%). Postoperative HOMA IR was significantly less after LRYGBP, 2.2 (0.7
      12.2), than LAGB, 2.6 (0.8-29.6), although change in HOMA IR was not
      significantly different. Change in HOMA IR for both groups did not vary with
      length of follow-up or weight loss but correlated best with preoperative HOMA IR
      (LAGB r=0.8264; LRYGBP r=0.9711). CONCLUSIONS: Both LAGB and LRYGBP significantly
      improved insulin resistance during the first 3 months following surgery. Both
      operations generated similar changes in HOMA IR, although postoperative HOMA IR
      levels were significantly lower after LRYGBP. These findings suggest that caloric
      restriction plays a significant role in improving insulin resistance after both
      LAGB and LRYGBP.

PMID- 16989704
TI  - Pre-surgery binge eating status: effect on eating behavior and weight outcome
      after gastric bypass.
AB  - BACKGROUND: The impact of pre-surgical binge eating on postoperative outcomes is
      poorly understood. Previous studies have found marked preoperative differences
      between binge eaters (BE) and non-binge eaters (NBE) in hunger and disinhibition
      using the Three-Factor Eating Questionnaire (TFEQ). Short-term prospective data
      are mixed regarding whether these differences persist after surgery and if
      preoperative binge eating impacts postoperative weight outcomes. The purpose of
      the present study was to compare self-reported eating behavior and weight
      outcomes between BE and NBE after the first postoperative year. METHODS: Prior to
      surgery, 72 Roux-en-Y gastric bypass (RYGBP) patients completed the Questionnaire
      of Eating and Weight Patterns (QEWP) or QEWP-Revised (QEWP-R), to assess binge
      eating status which was defined as one objective binge episode per week over the
      past 6 months. Subjects also completed the TFEQ prior to surgery and again > or =
      12 months after surgery. RESULTS: For BE, higher scores were found for both
      hunger and disinhibition prior to surgery. At a mean of 18 months after surgery,
      BE and NBE were indistinguishable on these subscales and there were no
      differences in weight lost. CONCLUSIONS: RYGBP surgery has an equally positive
      impact on eating behavior and weight loss for both BE and NBE. Within a
      multidisciplinary clinic, preoperative BE status does not appear to be a negative
      prognostic indicator for RYGBP surgery in the domains of weight loss and
      disinhibition. Further replication is needed with longer follow-up times and
      larger samples.

PMID- 16989705
TI  - Concurrent gastric bypass and repair of anterior abdominal wall hernias.
AB  - BACKGROUND: Many patients seeking surgical treatment for morbid obesity present
      with anterior abdominal wall hernias. Although principles of hernia repair
      involve a tension-free repair with the use of prosthetic mesh, there is concern
      about the use of mesh in gastric bypass surgery due to potential contamination
      with the contents of the gastrointestinal tract and resultant mesh infection. We
      report our series of patients undergoing Roux-en-Y gastric bypass (RYGBP) and
      simultaneous anterior abdominal wall hernia repair. METHODS: All patients who
      underwent simultaneous RYGBP surgery and anterior abdominal wall hernia repair
      were reviewed. RESULTS: 12 patients underwent concurrent RYGBP and anterior wall
      hernia repair. There were 5 women and 7 men with average age 54.9 +/- 8.5 years
      (range 35 to 64) and average body mass index (BMI) 50.4 +/- 10.3 kg/m(2) (range
      38 to 70). Two open and 10 laparoscopic RYGBP operations were performed. Nine
      patients (75%) underwent incisional hernia repairs and 3 patients (25%) underwent
      umbilical hernia repair concurrent with gastric bypass. Average size of defect
      was 14.7 +/- 13.4 cm(2). One patient had primary repair and 11 patients had
      prosthetic mesh repair: polypropylene in 3 patients (25%) and polyester in 8
      patients (67%). With a 14.1 +/- 9.3 month follow-up, there have been no mesh
      infections and 2 recurrences, one in the patient who underwent primary repair and
      one in a patient repaired with polyester mesh but with two previous failed
      incisional hernia repairs. CONCLUSION: Concurrent RYGBP and repair of anterior
      abdominal wall hernias is safe and feasible. In order to optimize success,
      tension-free principles of hernia repair with the use of prosthetic mesh should
      be followed since no mesh infections occurred in our series.

PMID- 16989706
TI  - Rhabdomyolysis after gastric bypass: severity and outcome patterns.
AB  - BACKGROUND: Rhabdomyolysis (RML) is a recently recognized complication of
      bariatric operations, but it is not known whether creatine kinase (CK) levels
      along with clinical markers are able to define the course and outcome. METHODS:
      Bariatric patients (n=324) were reviewed retrospectively. Substantially elevated
      plasma CK after operation was identified in 4.9% (16/324). The affected
      population was divided into Group I (n=11, 68.8%) with CK 1050-8000 IU/L and no
      conspicuous muscle pain, weakness or swelling, and Group II (n=5, 31.2%)
      displaying CK >8000 IU/L and severe pain and dysfunction. The main outcome
      measures were CK concentration, frequency of renal failure, need for hemodialysis
      and mortality. RESULTS: Group I subjects compared to Group II were younger (37.7
      +/- 10.9 vs 44.0 +/- 5.5 years, P<0.05) and predominantly females (72.7% vs
      40.0%, P<0.05). Peak CK values were definitely lower (2811 +/- 952 vs 28136 +/-
      19000 IU/L, P<0.001), and none progressed to renal failure (0% vs 40.0%, P<0.05).
      No difference was detected regarding preoperative BMI (50.8 +/- 8.1 vs 54.6 +/-
      7.0 kg/m(2), NS), duration of operation (5.3 +/- 1.6 vs 5.6 +/- 2.1 hours, NS) or
      types of anesthetic drugs (basically fentanyl, nitrogen oxide and
      halothane/isoflurane). CONCLUSIONS: 1) Demographic features, nominally gender and
      age, were different between the two degrees of RML; 2) Renal failure and
      hemodialysis were a danger only in patients with massive CK elevation and muscle
      pain; 3) Moderate CK increase was very well tolerated and rarely entailed major
      clinical symptoms; 4) Early diagnosis, fluid replenishment and general supportive
      therapy probably contributed to avert mortality.

PMID- 16989707
TI  - Relationship of androgens to insulin resistance and chronic inflammation in
      morbidly obese premenopausal women: studies before and after vertical banded
      gastroplasty.
AB  - BACKGROUND: Morbid obesity is associated with insulin resistance (IR), type 2
      diabetes, lipid abnormalities, and hypertension. The association of obesity with
      increased androgen production and low concentrations of sex hormone-binding
      globulin (SHBG) in women has been demonstrated as well as a strong association of
      androgens with markers of inflammation such as high-sensitive C-reactive protein
      (hsCRP). Because weight loss results in a significant decrease in cardiovascular
      risk factors, IR and inflammation, we questioned a possible interrelationship
      between androgens, IR and inflammation in a prospective study with 43 morbidly
      obese female patients undergoing bariatric surgery. METHODS: SHBG,
      dehydroepiandrosterone-sulfate (DHEA-S), and insulin were measured by ELISA,
      cortisol by fluorescence polarization immunoassay, androstendione by RIA, and
      testosterone by electrochemiluminescence immunoassay. The free androgen index
      (FAI) was calculated as the total testosterone/SHBG ratio. High sensitivity
      assays were used to obtain concentrations of fasting hsCRP, Interleukin-6 (IL-6)
      and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Weight loss resulted in a
      significant increase in SHBG (17+/-12 vs 70+/-30 nmol/l, P<0.0001). Serum
      concentrations of androstendione, total testosterone, DHEA-S and the FAI
      decreased significantly (2.05+/-0.78 vs 1.40+/-0.54 ng/ml, P<0.0001; 1.88+/-0.84
      vs 1.16+/-0.57 nmol/L, P<0.0001; 1.72+/-0.86 vs 1.49+/-0.78 microg/ml, P<0.01;
      0.15+/-0.10 vs 0.02+/-0.01, P<0.0001; respectively). Preoperatively and
      postoperatively, no association between androgens and IR, chronic subclinical
      inflammation and lipid parameters could be observed. CONCLUSION: Massive weight
      loss induced by bariatric surgery is associated with a significant reduction of
      androgen concentrations but not related to the concomitant decline of chronic
      inflammation, IR, glucose and lipid abnormalities in premenopausal morbidly obese
      women.

PMID- 16989708
TI  - Efficacy of estradiol topical patch in the treatment of symptoms of depression
      following mini-gastric bypass in women.
AB  - BACKGROUND: Obesity is associated with elevated levels of estrogen. Gastric
      bypass causes rapid weight loss and decreased levels of estrogen. Patients after
      gastric bypass can suffer from anxiety and depression out of proportion to the
      surgical outcome. This study reports the efficacy of a short-term empiric trial
      of topical estradiol for the treatment of mild to moderate depression and anxiety
      following mini-gastric bypass (MGB) in women. METHODS: Postoperative MGB women
      were surveyed for the presence of depressive symptoms before and after MGB. The
      results of an empiric trial of transdermal patches of estradiol-17beta were
      assessed. Outcome measures were the self-reported efficacy of the patch. RESULTS:
      711 women who had undergone MGB and had functioning e-mail addresses made up the
      study. 62% of patients reported depression prior to surgery. 156 patients (22%)
      reported depression after the operation. 130 women were treated empirically with
      the patch, and remission of depression was observed in 92 (71%). In response to
      the question "Did the estrogen patch help?", subjects reported responses of 1)
      Yes, fantastic, 2) Yes, somewhat, 3) Hard to say, 4) No, in 36%, 31%, 20%, 13% of
      respondents respectively. Patients treated with estradiol sustained
      antidepressant benefit of treatment after the patch was discontinued. Treatment
      lasted <1 month, 1-3 months, and >3 months, in 48%, 32% and 20% respectively.
      Treatment was well-tolerated and adverse events were rare. CONCLUSION: Depression
      is common in obese patients and remains a problem in a subset following the MGB
      operation. Transdermal estradiol replacement appears to be an effective treatment
      of symptoms of depression in women following MGB.

PMID- 16989709
TI  - Predictors of weight status following laparoscopic gastric bypass.
AB  - BACKGROUND: Weight loss after bariatric surgery varies and depends on many
      factors, such as time elapsed since surgery, baseline weight, and co-morbidities.
      METHODS: We analyzed weight data from 494 patients who underwent laparoscopic
      Roux-en-Y gastric bypass (RYGBP) by one surgeon at an academic institution
      between June 1999 and December 2004. Linear regression was used to identify
      factors in predicting % excess weight loss (%EWL) at 1 year. RESULTS: Mean
      patient age at time of surgery was 44 +/- 9.6 (SD), and the majority were female
      (83.8%). The baseline prevalence of co-morbidities included 24% for diabetes, 42%
      for hypertension, and 15% for hypercholesterolemia. Baseline BMI was 51.5 +/- 8.5
      kg/m(2). Mean length of hospital stay was 3.8 +/- 4.6 days. Mortality rate was
      0.6%. Follow-up weight data were available for 90% of patients at 6 months after
      RYGBP, 90% at 1 year, and 51% at 2 years. Mean %EWL at 1 year was 65 +/- 15.2%.
      The success rate (> or = 50 %EWL) at 1 year was 85%. Younger age and lower
      baseline weight predicted greater weight loss. Males lost more weight than
      females. Diabetes was associated with a lower %EWL. Depression did not
      significantly predict %EWL. CONCLUSION: The study demonstrated a 65 %EWL and 85%
      success rate at 1 year in our bariatric surgery program. Our finding that most
      pre-surgery co-morbidities and depression did not predict weight loss may have
      implications for pre-surgery screening.

PMID- 16989710
TI  - Spectrum of endoscopic findings and therapy in patients with upper
      gastrointestinal symptoms after laparoscopic bariatric surgery.
AB  - BACKGROUND: More should be known about the spectrum of endoscopic abnormalities
      and treatments in patients with upper gastrointestinal (UGI) symptoms after
      laparoscopic bariatric surgery. METHODS: Patients referred for endoscopic
      evaluation of UGI symptoms after laparoscopic bariatric surgery were studied.
      Clinical manifestations, endoscopic findings and therapy were recorded and
      correlated. RESULTS: 76 patients who had undergone laparoscopic vertical banded
      gastroplasty (LVBG) and 28 who had undergone laparoscopic Roux-en-Y gastric
      bypass (LRYGBP) underwent 160 instances of upper endoscopy. The symptoms included
      nausea or vomiting (n=47, 29.4%), epigastric discomfort (n=44, 27.5%), UGI
      bleeding (n=26, 16.3%), heartburn or acid regurgitation (n=26, 16.3%), dysphagia
      (n=10, 6.3%) and anemia with dizziness (n=7, 4.4%). The endoscopic diagnosis
      consisted of normal findings (n=57, 35.6%), marginal ulcer (n=39, 24.4%), erosive
      esophagitis or esophageal ulcer (n=21, 13.1%), food impaction (n=21, 13.1%),
      stenosis or stricture (n=14, 8.8%), gastric ulcer (n=7, 4.4%), and duodenal ulcer
      (n=1, 0.6%). Patients with UGI bleeding, dysphagia and LRYGBP tended to have
      endoscopic abnormalities (P<0.001, P=0.09 and P=0.021, respectively). Endoscopic
      therapy was successful in resolving the complications including stenosis, UGI
      bleeding and food impaction. CONCLUSIONS: Endoscopy is an essential method of
      combining relevant endoscopic findings and therapeutic intervention in
      symptomatic patients following laparoscopic bariatric surgery.

PMID- 16989711
TI  - Charcoal peritonitis causing chronic pelvic pain: a unique complication following
      bariatric surgery.
AB  - Routine pathologic examination of a specimen transformed a common diagnosis of
      endometriosis into a search for an unusual cause of recurrent pelvic pain.
      Laparoscopy was suspicious for endometriosis, but instead on microscopic
      examination a black pigment of unknown origin was present. In a subsequent
      interview with her gynecologist the 38-year-old patient divulged a previous Roux
      en-Y gastric bypass (RYGBP), followed 8 weeks later by a suicide attempt by
      overdosing on medication, treated with charcoal gastric lavage. Her tiny gastric
      pouch was perforated and she developed charcoal peritonitis. If the emergency
      room physicians had been aware of her recent RYGBP, they may not have performed
      the lavage, and if the gynecologist had been aware of the history, she may not
      have been incorrectly diagnosed endometriosis.

PMID- 16989712
TI  - Gastro-ileal stenosis and gastroparesis after a biliopancreatic diversion.
AB  - Biliopancreatic diversion (BPD) is a very effective bariatric operation
      particularly for super-obese patients (BMI > or = 50 kg/m(2)). We present the
      development of a stricture at the gastro-ileal anastomotic site, with subsequent
      dilatation and aperistalsis of the stomach in a female patient who had undergone
      a standard open Scopinaro BPD. The patient remained symptomatic and persisted in
      losing weight, despite endoscopic balloon dilatations of the stricture and
      surgical revision of the anastomosis. She finally underwent conversion to a
      standard Roux-en-Y proximal gastric bypass. We describe the development of the
      stricture after the use of the stapling gun, subsequent gastric dilatation and
      dysmotility.

PMID- 16989713
TI  - Internal hernia with Roux loop obstruction during pregnancy after gastric bypass
      surgery.
AB  - We report the rare case of a pregnant woman who had undergone Roux-en-Y gastric
      bypass 8 months previously, and now presented with subacute small bowel
      obstruction secondary to internal herniation of some of the proximal Roux limb
      into the lesser sac through the transverse mesocolon rent, which was widely
      spread apart. At laparoscopy, the hernia contents were reduced and the defect was
      repaired. The patient made a good recovery. Because of the changes associated
      with pregnancy, gastric bypass patients may be at an increased risk of internal
      herniation. It is particularly important not to delay surgical exploration, even
      in the absence of a positive finding on imaging, because delay may lead to
      potentially devastating bowel strangulation and sepsis culminating in loss of
      fetus and mother.

PMID- 16989714
TI  - Small bowel diverticulitis of the Roux loop after gastric bypass.
AB  - The epidemic of obesity and the introduction of laparoscopic techniques have
      greatly increased the popularity of bariatric operations such as Roux-en-Y
      gastric bypass (RYGBP). Acquired diverticular disease of the small bowel is a
      rare condition that becomes symptomatic in about 10% of the cases. We report a 48
      year-old morbidly obese woman who presented 2 months after laparoscopic RYGBP
      with a perforated diverticulum of the Roux loop. The diagnostic and therapeutic
      implications are discussed.

PMID- 16989715
TI  - Laparoscopic Roux-en-Y gastric bypass in patients with congenital malrotation.
AB  - Bariatric surgery is the only solution for morbidly obese individuals who desire
      to lose weight and maintain it and have failed to do so by non-surgical means. As
      the incidence of morbid obesity rises, laparoscopic Roux-en-Y gastric bypass
      (LRYGBP) is increasingly performed. With the increase in bariatrics, the chances
      of discovering aberrant anatomy at the operating-table also increase. We present
      two cases of LRYGBP in patients with intestinal malrotation, which is a
      congenital anomaly caused by failure of the intestines to rotate and fixate at
      270 degrees during embryonic development. It occurs in one out of every 500
      births in the United States, accounting for 5% of all intestinal obstructions. To
      this date, only three reports have been published describing the incidental
      finding of congenital malrotation during the initial laparoscopic exploration for
      gastric bypass. We found that the operation can still be performed
      laparoscopically in such patients, with some modifications to the standard
      technique.

PMID- 16989716
TI  - Safe intestinal decompression in fresh postoperative gastric bypass.
AB  - BACKGROUND: Dilatation of the Roux-limb is sometimes found following Roux-en-Y
      gastric bypass (RYGBP) procedures. This could be the result of a transient
      episode due to ileus, or a partial or complete obstruction. The risk of this
      complication is an increase in intraluminal pressure with the potential for leak.
      Blind insertion of a nasogastric tube for decompression could be risky due to
      possible perforation at the stapled or sutured edges. METHODS AND RESULTS: The
      diagnosis was made with routine extended upper gastrointestinal x-rays 24 hours
      after surgery. To determine the relationship of the intestinal dilatation,
      increase in intraluminal pressures and leaks, measurements were taken in porcine
      models duplicating a RYGBP. Pressures obtained at the anastomoses were higher
      than pressures in the jejunum between the anastomoses, and related directly to
      the production of leaks. Elevations of intraluminal intestinal pressures have
      also been observed in patients who required decompression. The angles of a
      freshly constructed pouch and the recent stapled or sutured edges may be easily
      perforated with a nasogastric tube, especially a hard one. We use a soft flexible
      tube. An angled-end 0.035" wire is introduced into the intestines with
      fluoroscopic assistance. The tube tip is perforated with a needle, and through
      this opening, the wire is passed into the tube. The tube is then fed over the
      wire for safe decompression. CONCLUSION: Decreasing the intestinal pressure by
      safe decompression may avoid one of the causes of leaks.

PMID- 16989717
TI  - Analysis of the vertical isolated gastroplasty: a new bariatric operation.

PMID- 16989719
TI  - Epigenetics: a major cause of variations on the same theme.

PMID- 16989721
TI  - The history of tissue engineering.

PMID- 16989720
TI  - Epigenetic boundaries of tumour suppressor gene promoters: the CTCF connection
      and its role in carcinogenesis.
AB  - Genetic and epigenetic regulations are essential mechanisms that ensure proper
      early and subsequent mammalian programming of diverse cellular processes. These
      mechanisms affect transcriptional regulation, stem cell determination and cell
      cycle control, including senescence and aging. It is not surprising that
      perturbation of the exquisite balance between genetic and epigenetic regulation
      can lead to diverse diseases, including cancer. Histone covalent modifications
      and DNA methylation do not explain all epigenetic phenomena. We describe a
      previously unsuspected epigenetic factor and propose the incorporation of the 11
      zinc finger CCCTC-binding factor, known as CTCF as a novel and multifunctional
      epigenetic regulator.

PMID- 16989722
TI  - Fetal and adult liver stem cells for liver regeneration and tissue engineering.
AB  - For the development of innovative cell-based liver directed therapies, e.g. liver
      tissue engineering, the use of stem cells might be very attractive to overcome
      the limitation of donor liver tissue. Liver specific differentiation of
      embryonic, fetal or adult stem cells is currently under investigation. Different
      types of fetal liver (stem) cells during development were identified, and their
      advantageous growth potential and bipotential differentiation capacity were
      shown. However, ethical and legal issues have to be addressed before using fetal
      cells. Use of adult stem cells is clinically established, e.g. transplantation of
      hematopoietic stem cells. Other bone marrow derived liver stem cells might be
      mesenchymal stem cells (MSC). However, the transdifferentiation potential is
      still in question due to the observation of cellular fusion in several in vivo
      experiments. In vitro experiments revealed a crucial role of the environment
      (e.g. growth factors and extracellular matrix) for specific differentiation of
      stem cells. Co-cultured liver cells also seemed to be important for hepatic gene
      expression of MSC. For successful liver cell transplantation, a novel approach of
      tissue engineering by orthotopic transplantation of gel-immobilized cells could
      be promising, providing optimal environment for the injected cells. Moreover, an
      orthotopic tissue engineering approach using bipotential stem cells could lead to
      a repopulation of the recipients liver with healthy liver and biliary cells, thus
      providing both hepatic functions and biliary excretion. Future studies have to
      investigate, which stem cell and environmental conditions would be most suitable
      for the use of stem cells for liver regeneration or tissue engineering
      approaches.

PMID- 16989723
TI  - In vivo models of angiogenesis.
AB  - The process of building new blood vessels (angiogenesis) and controlling the
      propagation of blood vessels (anti-angiogenesis) are fundamental to human health,
      as they play key roles in wound healing and tissue growth. More than 500 million
      people may stand to benefit from anti- or pro-angiogenic treatments in the coming
      decades [National Cancer Institute (USA), Cancer Bulletin, volume 3, no. 9,
      2006]. The use of animal models to assay angiogenesis is crucial to the search
      for therapeutic agents that inhibit angiogenesis in the clinical setting.
      Examples of persons that would benefit from these therapies are cancer patients,
      as cancer growth and spread is angiogenesis-dependent, and patients with aberrant
      angiogenesis in the eye, which may lead to blindness or defective sight.
      Recently, anti-angiogenesis therapies have been introduced successfully in the
      clinic, representing a turning point in tumor therapy and the treatment of
      macular degeneration and heralding a new era for the treatment of several
      commonly occurring angiogenesis-related diseases. On the other hand, pro
      angiogenic therapies that promote compensatory angiogenesis in hypoxic tissues,
      such as those subjected to ischemia in myocardial or cerebral hypoxia due to
      occluding lesions in the coronary or cerebral arteries, respectively, and in
      cases of poor wound healing, are also being developed. In this review, the
      current major and newly introduced preclinical angiogenesis assays are described
      and discussed in terms of their specific advantages and disadvantages from the
      biological, technical, economical and ethical perspectives. These assays include
      the corneal micropocket, chick chorioallantoic membrane, rodent mesentery,
      subcutaneous (s.c.) sponge/matrix/alginate microbead, s.c. Matrigel plug, s.c.
      disc, and s.c. directed in vivo angiogenesis assays, as well as, the zebrafish
      system and several additional assays. A note on quantitative techniques for
      assessing angiogenesis in patients is also included. The currently utilized
      preclinical assays are not equivalent in terms of efficacy or relevance to human
      disease. Some of these assays have significance for screening, while others are
      used primarily in studies of dosage-effects, molecular structure activities, and
      the combined effects of two or more agents on angiogenesis. When invited to write
      this review, I was asked to describe in some detail the rodent mesenteric-window
      angiogenesis assay, which has not received extensive coverage in previous
      reviews.

PMID- 16989724
TI  - What is hidden in the pannexin treasure trove: the sneak peek and the guesswork.
AB  - Connexins had been considered to be the only class of the vertebrate proteins
      capable of gap junction formation; however, new candidates for this function with
      no homology to connexins, termed pannexins were discovered. So far three
      pannexins were described in rodent and human genomes: Panx1, Panx2 and Panx3.
      Expressions of pannexins can be detected in numerous brain structures, and now
      found both in neuronal and glial cells. Hypothetical roles of pannexins in the
      nervous system include participating in sensory processing, hippocampal
      plasticity, synchronization between hippocampus and cortex, and propagation of
      the calcium waves supported by glial cells, which help maintain and modulate
      neuronal metabolism. Pannexin also may participate in pathological reactions of
      the neural cells, including their damage after ischemia and subsequent cell
      death. Recent study revealed non-gap junction function of Panx1 hemichannels in
      erythrocytes, where they serve as the conduits for the ATP release in response to
      the osmotic stress. High-throughput studies produced some evidences of the
      pannexin involvement in the process of tumorigenesis. According to brain cancer
      gene expression database REMBRANDT, PANX2 expression levels can predict post
      diagnosis survival for patients with glial tumors. Further investigations are
      needed to verify or reject hypotheses listed.

PMID- 16989725
TI  - Stabilin-1, a homeostatic scavenger receptor with multiple functions.
AB  - The multifunctional scavenger receptor stabilin-1 (STAB1, FEEL-1, CLEVER-1,
      KIAA0246) was originally identified as the MS-1 antigen, expressed by sinusoidal
      endothelial cells in human spleen. Extensive histological studies revealed that
      stabilin-1 is also expressed by tissue macrophages and sinusoidal endothelial
      cells in the healthy organism; its expression on both macrophages and different
      subtypes of endothelial cells is induced during chronic inflammation and
      tumorigenesis. In vitro induction of stabilin-1 in macrophages requires the
      presence of glucocorticoids. Stabilin-1 is involved in two intracellular
      trafficking pathways: receptor mediated endocytosis and recycling; and shuttling
      between the endosomal compartment and trans-Golgi network (TGN). The latter
      intracellular pathway of stabilin-1 trafficking is mediated by GGAs, clathrin
      adaptors that interact with the DDSLL motif in the cytoplasmic tail of stabilin
      1. When expressed by alternatively activated macrophages, stabilin-1 mediates the
      uptake and targeting for degradation of acLDL and SPARC, a regulator of tissue
      remodeling. Likewise, stabilin-1 in macrophages is involved in intracellular
      sorting and lysosomal delivery of the novel stabilin- 1-interacting chitinase
      like protein (SI-CLP). Indirect evidence suggests that stabilin-1 is involved in
      adhesion and transmigration in various cell types (including tumor cells,
      leukocytes, and lymphocytes); however, its rapid recycling and scant level of
      surface expression argue against its universal role in cell adhesion. In summary,
      stabilin-1 is a homeostatic receptor which links signals from the extracellular
      environment to intracellular vesicular processes, creating a potential impact on
      the macrophage secretion profile.

PMID- 16989726
TI  - Protective effect of carbon monoxide in transplantation.
AB  - During the last decades due to the development of new immunosuppressive agents
      and improvements in organ preservation methods, surgical techniques, and
      postoperative care, organ transplantation has become an ultimate therapeutic
      option for irreversible organ failure. Early graft survival has significantly
      improved; however, the long-term outcome remains unsatisfactory. Multiple
      factors, both immunogenic and non-immunogenic etiologies, are involved in the
      deterioration of the allografts, and the recent use of expanded criteria donors
      to overcome the organ shortage may also contribute to the graft losses. Carbon
      monoxide (CO) is commonly viewed as a poison in high concentrations due to its
      ability to interfere with oxygen delivery. However, CO is endogenously produced
      in the body as a byproduct of heme degradation by the heme oxygenase (HO) and has
      recently received notable attention as a gaseous regulatory molecule. In fact, an
      augmentation of endogenous CO by induction of HO-1 or exogenously added CO is
      known to have potent cytoprotective effects in various disease models. Several
      recent reports have demonstrated that CO provides potent cytoprotective effects
      in the field of organ and cell transplantation. CO is able to prevent
      ischemia/reperfusion injury, allograft rejection, and xenograft rejection via its
      anti-inflammatory, anti-apoptotic and anti-proliferation effects, suggesting that
      CO might be a valuable therapeutic option in the field of transplantation. Based
      on the recent advancement of our understanding of CO as a new therapeutic
      molecule, this review attempts to summarize the functional roles as well as
      biological and molecular mechanisms of CO in transplantation and discusses
      potential CO application to the clinical transplant setting.

PMID- 16989727
TI  - Role of carbon monoxide in cardiovascular function.
AB  - Carbon monoxide (CO) is an endogenously derived gas formed from the breakdown of
      heme by the enzyme heme oxygenase. Although long considered an insignificant and
      potentially toxic waste product of heme catabolism, CO is now recognized as a key
      signaling molecule that regulates numerous cardiovascular functions.
      Interestingly, alterations in CO synthesis are associated with many
      cardiovascular disorders, including atherosclerosis, septic shock, hypertension,
      metabolic syndrome, and ischemia-reperfusion injury. Significantly, restoration
      of physiologic CO levels exerts a beneficial effect in many of these settings,
      suggesting a crucial role for CO in maintaining cardiovascular homeostasis. In
      this review, we outline the actions of CO in the cardiovascular system and
      highlight this gas as a potential therapeutic target in treating a multitude of
      cardiovascular disorders.

PMID- 16989728
TI  - IL-9 enhances growth of ICC, maintains network structure and strengthens
      rhythmicity of contraction in culture.
AB  - Interstitial cells of Cajal (ICC) play a critical role in the control of
      gastrointestinal motility as pacemaker cells and as regulators of enteric
      innervation. ICC are one of the first cell types that are injured during an
      inflammatory process and maintenance of ICC health or promotion of growth and
      development maybe crucial in recovery after injury. The aim of this study was to
      evaluate the role of IL-9 in the growth, development and maintenance of ICC in
      culture. IL-9 in concentrations from 0.02 to 1 microg/ml promoted individual ICC
      growth and maintenance of the ICC network structure inside tissue explants under
      culture conditions. The number of ICC grown out of the explants increased
      significantly at day 4 of culture in the presence of 0.02, 0.5 and 1 microg/ml IL
      9. In the presence of 0.5 microg/ml IL-9, explants in culture maintained a higher
      frequency and stabilized the frequency of spontaneous contractile activity. The
      ultrastructure of the ICC after 4 days in culture was similar to that in situ.
      Our data indicate that IL-9 promotes ICC growth in culture and it can be
      hypothesized that IL-9 is a critical factor in the maintenance of ICC health and
      ICC repair after injury.

PMID- 16989729
TI  - Evaluation of processed bovine cancellous bone matrix seeded with syngenic
      osteoblasts in a critical size calvarial defect rat model.
AB  - INTRODUCTION: Biologic bone substitutes may offer alternatives to bone grafting
      procedures. The aim of this study was to evaluate a preformed bone substitute
      based on processed bovine cancellous bone (PBCB) with or without osteogenic cells
      in a critical size calvarial defect rat model. METHODS: Discs of PBCB (Tutobone)
      were seeded with second passage fibrin gel-immobilized syngenic osteoblasts
      (group A, n = 40). Cell-free matrices (group B, n = 28) and untreated defects
      (group C; n=28) served as controls. Specimens were explanted between day 0 and 4
      months after implantation and were subjected to histological and morphometric
      evaluation. RESULTS: At 1 month, bone formation was limited to small peripheral
      areas. At 2 and 4 months, significant bone formation, matrix resorption as well
      as integration of the implants was evident in groups A and B. In group C no
      significant regeneration of the defects was observed. Morphometric analysis did
      not disclose differences in bone formation in matrices from groups A and B.
      Carboxyfluorescine-Diacetate-Succinimidylester (CFDA) labeling demonstrated low
      survival rates of transplanted cells. DISCUSSION: Osteoblasts seeded into PBCB
      matrix display a differentiated phenotype following a 14 days cell culture
      period. Lack of initial vascularization may explain the absence of added
      osteogenicity in constructs from group A in comparison to group B. PBCB is well
      integrated and represents even without osteogenic cells a promising biomaterial
      for reconstruction of critical size calvarial bone defects.

PMID- 16989730
TI  - A subpopulation of peritoneal macrophages form capillarylike lumens and branching
      patterns in vitro.
AB  - OBJECTIVE: We have previously shown that monocytes/macrophages (MC/Mph) influence
      neovascularization by extracellular matrix degradation, and by direct
      incorporation into growing microvessels. To date, neither the phenotype of these
      cells, nor the stages of their capillary-like conversion were sufficiently
      characterized. METHODS: We isolated mouse peritoneal Mph from transgenic mice
      expressing fluorescent proteins either ubiquitously, or specifically in the
      myelocytic lineage. These Mph were embedded in Matrigel which contained
      fluorescent protease substrates, exposed to an MCP-1 chemotactic gradient, and
      then examined by confocal microscopy after various intervals. RESULTS: Within 3
      hrs after gel embedding, we detected TIMP-1 and MMP-12 dependent proteolysis of
      the matrix surrounding Mph, mostly in the direction of high concentrations of MCP
      1. After 2 days, Mph developed intracellular vacuoles containing degradation
      product. At 5 days these vacuoles were enlarged and/or fused to generate trans
      cellular lumens in approximately 10% of cells or more (depending on animal's
      genetic background). At this stage, Mph became tubular, and occasionally
      organized in three-dimensional structures resembling branched microvessels.
      CONCLUSION: Isolated mouse peritoneal Mph penetrate Matrigel and form tunnels via
      a metalloprotease-driven proteolysis and phagocytosis. Following a morphological
      adjustment driven by occurrence, enlargement and/or fusion process of
      intracellular vacuoles, similar to that described in bona fide endothelium, a
      subpopulation of these cells end up by lining a capillary-like lumen in vitro.
      Thus we show that adult Mph, not only the more primitive 'endothelial
      progenitors', have functional properties until now considered defining of the
      endothelial phenotype.

PMID- 16989731
TI  - A new approach to tissue engineering of vascularized skeletal muscle.
AB  - Tissue Engineering of skeletal muscle tissue still remains a major challenge.
      Every neo-tissue construct of clinically relevant dimensions is highly dependent
      on an intrinsic vascularisation overcoming the limitations of diffusion
      conditioned survival. Approaches incorporating the arteriovenous-loop model might
      bring further advances to the generation of vascularised skeletal muscle tissue.
      In this study 12 syngeneic rats received transplantaion of carboxy-fluorescine
      diacetate-succinimidyl ester (CFDA)-labelled, expanded primary myoblasts into a
      previously vascularised fibrin matrix, containing a microsurgically created AV
      loop. As control cells were injected into fibrin-matrices without AV-loops. Intra
      arterial ink injection followed by explantation was performed 2, 4 and 8 weeks
      after cell implantation. Specimens were evaluated for CFDA, MyoD and DAPI
      staining, as well as for mRNA expression of muscle specific genes. Results showed
      enhanced fibrin resorption in dependence of AV loop presence. Transplanted
      myoblasts could be detected in the AV loop group even after 8 weeks by CFDA
      fluorescence, still showing positive MyoD staining. RT-PCR revealed gene
      expression of MEF-2 and desmin after 4 weeks on the AVloop side, whereas
      expression analysis of myogenin and MHC(embryo) was negative. So far myoblast
      injection in the microsurgical rat AV loop model enhances survival of the cells,
      keeping their myogenic phenotype, within pre-vascularised fibrin matrices.
      Probably due to the lack of potent myogenic stimuli and additionally the rapid
      resorption of the fibrin matrix, no formation of skeletal muscle-like tissue
      could be observed. Thus further studies focussing on long term stability of the
      matrix and the incorporation of neural stimuli will be necessary for generation
      of vascularised skeletal muscle tissue.

PMID- 16989732
TI  - Intracoronary infusion of autologous bone marrow cells and left ventricular
      function after acute myocardial infarction: a meta-analysis.
AB  - Recent clinical studies have demonstrated that intracoronary infusion of
      autologous bone marrow cells (BMC) in conjunction with standard treatment may
      improve left ventricular function after an acute myocardial infarction (AMI).
      However, the results of these studies remain controversial, as the studies were
      relatively small in size and partially differed in design. We reviewed primary
      controlled randomized clinical studies comparing intracoronary transfer of
      autologous non-mobilized BMC combined with standard therapy versus standard
      therapy alone in patients with AMI. We identified five randomized controlled
      clinical trials, three of which were also placebo- and bone marrow aspiration
      controlled. Non-mobilized BMC were infused into the revascularized coronary
      target artery 6.6 +/- 6.1 days after AMI. The mean follow- up period of 5.2 +/-
      1.1 months was completed by 482 patients, 241 of which received infusion of BMC.
      The effect of BMC on left ventricular ejection fraction (LVEF) as a major
      functional parameter was evaluated. Analyzing the overall effect on the change in
      LVEF between baseline and follow-up value revealed a significant improvement in
      the BMCtreated group as compared to the control group (P = 0.04). Thus,
      considering the increase in LVEF during follow-up, transplantation of BMC may be
      a safe and beneficial procedure to support treatment of AMI. However, the
      functional improvement observed with this form of therapy was altogether
      relatively moderate and the studies were heterogeneous in design. Hence, further
      efforts aiming at large-scale, double-blind, randomized and placebo-controlled
      multi-center trials in conjunction with better definition of patients, which
      benefit from BMC infusion, appear to be warranted.

PMID- 16989733
TI  - Angiotensin II-induced delayed stimulation of phospholipase C gamma1 requires
      activation of both phosphatidylinositol 3-kinase gamma and tyrosine kinase in
      vascular myocytes.
AB  - In vascular smooth muscles, angiotensin II (AII) has been reported to activate
      phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3K). We investigated
      the time-dependent effects of AII on both phosphatidylinositol 3,4,5
      trisphosphate (PtdInsP3) and inositol phosphates (InsPs) accumulation in
      permeabilized microsomes from rat portal vein smooth muscle in comparison with
      those of noradrenaline (NA). AII stimulated an early production of PtdInsP3
      (within 30 s) followed by a delayed production of InsPs (within 3-5 min), in
      contrast to NA which activated only a fast production of InsPs. The use of
      pharmacological inhibitors and antibodies raised against the PI3K and PLC
      isoforms expressed in portal vein smooth muscle showed that AII specifically
      activated PI3Kgamma and that this isoform was involved in the AII-induced
      stimulation of InsPs accumulation. NA-induced InsPs accumulation depended on
      PLCbeta1 activation whereas AII-induced InsPs accumulation depended on PLCgamma1
      activation. AII-induced PLCgamma1 activation required both tyrosine kinase and
      PI3Kgamma since genistein and tyrphostin B48 (inhibitors of tyrosine kinase),
      LY294002 and wortmannin (inhibitors of PI3K) and anti-PI3Kgamma antibody
      abolished AII-induced stimulation of InsPs accumulation. Increased tyrosine
      phosphorylation of PLCgamma1 was only detected for long-lasting applications of
      AII and was suppressed by genistein. These data indicate that activation of both
      PI3Kgamma and tyrosine kinase is a prerequisite for AII-induced stimulation of
      PLCgamma1 in vascular smooth muscle and suggest that the sequential activation of
      the three enzymes may be responsible for the slow and long-lasting contraction
      induced by AII.

PMID- 16989734
TI  - Proliferation rate of human osteoblast-like cells on alloplastic biomaterials and
      their clinical application for the transnasal duraplasty procedure.
AB  - The possibility of transmission of slow virus infection (HIV) and Creutzfeld
      Jakob disease by cadaveric dura implants makes it necessary to find synthetic,
      absorbable materials for the reconstruction of the dura mater. Various procedures
      with autologous or alloplastic material are described. Four commercially
      available biomaterials were choosen to study the proliferation rate and the
      biocompatibility of human osteoblast-like cells (HOB-like cells) on 2-
      dimensional material by biochemical analysis. With a proliferation assay, the
      viability and the proliferation capacity of osteoblast-like cells were evaluated.
      A clinical trial was added to study resorbable fleece as one of the previously
      tested biomaterial in a small patient group (8 patients) to close anterior
      cranial fossa dura defects. The results of the proliferation assay showed the
      highest proliferation rate of HOB-like cells on resorbable fleece. All patients
      in our clinical trial with anterior cranial fossa dura defects were successfully
      treated with resorbable fleece. There was no evidence for persisting
      cerebrospinal fluid rhinorrhea or foreign body reaction after the period of wound
      healing. The present study demonstrated an excellent biocompatibility of
      resorbable fleece. The vicryl fleece is an alternative alloplastic material for
      endonasal closure of defined substantial defects of the dura with cerebrospinal
      fluid.

PMID- 16989735
TI  - Increase in decorin and biglycan in Duchenne Muscular Dystrophy: role of
      fibroblasts as cell source of these proteoglycans in the disease.
AB  - Fibrosis is a common pathological feature observed in muscles of patients with
      Duchenne muscular dystrophy (DMD). Biglycan and decorin are small
      chondroitin/dermatan sulfate proteoglycans in the muscle extracellular matrix
      (ECM) that belong to the family of structurally related proteoglycans called
      small leucine-rich repeat proteins. Decorin is considered an anti-fibrotic agent,
      preventing the process by blocking TGF-beta activity. There is no information
      about their expression in DMD patients. We found an increased amount of both
      proteoglycans in the ECM of skeletal muscle biopsies obtained from DMD patients.
      Both biglycan and decorin were augmented in the perimysium of muscle tissue, but
      only decorin increased in the endomysium as seen by immunohistochemical analyses.
      Fibroblasts were isolated from explants obtained from muscle of DMD patients and
      the incorporation of radioactive sulfate showed an increased synthesis of both
      decorin and biglycan in cultured fibroblasts compared to controls. The size of
      decorin and biglycan synthesized by DMD and control fibroblasts seems to be
      similar in size and anion charge. These findings show that decorin and biglycan
      are increased in DMD skeletal muscle and suggest that fibroblasts would be, at
      least, one source for these proteoglycans likely playing a role in the muscle
      response to dystrophic cell damage.

PMID- 16989736
TI  - Use of spider silk fibres as an innovative material in a biocompatible artificial
      nerve conduit.
AB  - Defects of peripheral nerves still represent a challenge for surgical nerve
      reconstruction. Recent studies concentrated on replacement by artificial nerve
      conduits from different synthetic or biological materials. In our study, we
      describe for the first time the use of spider silk fibres as a new material in
      nerve tissue engineering. Schwann cells (SC) were cultivated on spider silk
      fibres. Cells adhered quickly on the fibres compared to polydioxanone
      monofilaments (PDS). SC survival and proliferation was normal in Live/Dead
      assays. The silk fibres were ensheathed completely with cells. We developed
      composite nerve grafts of acellularized veins, spider silk fibres and SC diluted
      in matrigel. These artificial nerve grafts could be cultivated in vitro for one
      week. Histological analysis showed that the cells were vital and formed distinct
      columns along the silk fibres. In conclusion, our results show that artificial
      nerve grafts can be constructed successfully from spider silk, acellularized
      veins and SC mixed with matrigel.

PMID- 16989738
TI  - Interstitial Cajal-like cells (ICLC) as steroid hormone sensors in human
      myometrium: immunocytochemical approach.
AB  - Expression of estrogen (ER) and progesterone (PR) receptors was investigated in
      cultured human normal myometrial cells (non-pregnant uterus, fertile period). The
      ER and PR expression was studied by immunohistochemistry and immunofluorescence
      on either myocytes or interstitial Cajal-like cells (ICLC). Only those cells
      double immunostained for c-kit and steroid receptors were considered as ICLC. ER
      and/or PR immunoreactivity was localized in ICLC, primarily concentrated at the
      nucleus level, but it was also observed in the cell body (cytoplasm) and
      processes. Stronger immunopositive reaction in the ICLC nucleus for PR than for
      ER was noted. Under our experimental conditions, a clear positive repeatable
      reaction for steroid receptors could not be detected in myocytes. In conclusion,
      these data suggest that ICLC could be true hormonal 'sensors', possibly
      participating in the regulation of human myometrial contractions (via gap
      junctions with myocytes and/or by paracrine signaling).

PMID- 16989737
TI  - Analysis of p16 expression and allelic imbalance / loss of heterozygosity of 9p21
      in cutaneous squamous cell carcinomas.
AB  - Deletions of the short arm of chromosome 9 have been reported in different types
      of malignancies. This chromosomal region contains a number of known tumour
      suppressor genes, including the p16INK4A (CDKN2A), p15INK4B and MTAP tumour
      suppressor genes located at 9p21. In this study twenty-two paraffin embedded
      invasive cutaneous SCC were examined for allelic imbalance/ loss of
      heterozygosity (AI/LOH) of the 9p region (in particular 9p21), and for p16
      protein expression. DNA was isolated from microdissected sections of normal and
      tumour cells and analysed for AI/LOH by using six fluorescently labelled
      microsatellite markers that map to the 9p region. P16 protein expression was
      examined by immunohistochemistry. At each of the six microsatellite markers the
      majority of SCC analysed showed AI/LOH. Overall both AI/LOH within the CDKN2A
      locus and absence of p16 protein expression were frequent among the cutaneous SCC
      analysed, suggesting that p16 inactivation may play a role in cutaneous SCC
      development. The majority of the SCC analysed also had AI/LOH of the marker
      within the MTAP gene, and at markers flanking the CDKN2A gene; thus further
      investigation as to a possible role for these genes in the development of
      cutaneous SCC is warranted.

PMID- 16989740
TI  - Updated guidelines on cough launched.

PMID- 16989741
TI  - Effects of continuous tracheal gas insufflation during pressure limited
      ventilation on pulmonary surfactant in rabbits with acute lung injury.
AB  - BACKGROUND: Pulmonary surfactant dysfunction may contribute to the development of
      ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a
      technique in which fresh gas is introduced into the trachea and augment
      ventilation by reducing the dead space of ventilatory system, reducing
      ventilatory pressures and tidal volume (V(T)) while maintaining constant partial
      arterial CO2 pressure (PaCO(2)). We hypothesised that TGI limited peak
      inspiratory pressure (PIP) and V(T) and would minimize conventional mechanical
      ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate
      VILI in rabbits with acute lung injury (ALI). METHODS: ALI was induced by
      intratracheal administration of lipopolysaccharide in anaesthetized, ventilated
      healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI
      group) or CMV group (n = 8 for each group), and subsequently ventilated with
      limited PIP and V(T) to maintain PaCO(2) within 35 to 45 mmHg for 4 hours.
      Physiological dead space to V(T) ratio (V(D)/V(T)), dynamic respiratory
      compliance (Cdyn) and partial arterial O(2) pressure (PaO(2)) were monitored.
      After ventilation, lungs were analysed for total phospholipids (TPL), total
      proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in
      bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume
      density (V(V)), myeloperoxidase and interleukin (IL)-8. RESULTS: TGI resulted in
      significant (P < 0.05 or P < 0.01) decrease in PIP [(22.4 +/- 1.8) cmH2O vs (29.5
      +/- 1.1) cmH2O], V(T) [(6.9 +/- 1.3) ml/kg vs (9.8 +/- 1.11) ml/kg], V(D)/V(T)
      [(32 +/- 5)% vs (46 +/- 2)%], TP [(109 +/- 22) mg/kg vs (187 +/- 25) mg/kg],
      SA/LA (2.5 +/- 0.4 vs 5.4 +/- 0.7), myeloperoxidase [(6.2 +/- 0.5) U/g tissue vs
      (12.3 +/- 0.8) U/g tissue] and IL-8 [(987 +/- 106) ng/g tissue vs (24 +/- 3)
      mN/m] of BALF, and significant (P < 0.05) increase in Cdyn [(0.47 +/- 0.02)
      ml.cmH2O(-1).kg(-1) vs (0.31 +/- 0.02) ml.cmH2O(-1).kg(-1)], PaO(2) [(175 +/- 24)
      mmHg vs (135 +/- 26) mmHg], TPL/TP (52 +/- 8 vs 33 +/- 11) and Vv (0.65 +/- 0.05
      vs 0.44 +/- 0.07) as compared with CMV. CONCLUSIONS: In this animal model of ALI,
      TGI decreased ventilatory requirements (PIP, V(T) and V(D)/V(T)), resulted in
      more favourable alveolar pulmonary surfactant composition and function and less
      severity of lung injury than CMV. TGI in combination with pressure limited
      ventilation may be a lung protective strategy for ALI.

PMID- 16989742
TI  - Impaired upregulation of keratinocyte growth factor in injured lungs induced by
      Pseudomonas aeruginosa in immunosuppressed rats.
AB  - BACKGROUND: The number of immunosuppressed patients has increased in the past
      decades. Among them Pseudomonas aeruginosa (P. aeruginosa) is one of the leading
      bacteria for pneumonia that are associated with poor prognosis. However, the
      pathogenesis of P. aeruginosa pneumonia in immunosuppressed patients is not
      understood completely. Previous reports showed keratinocyte growth factor (KGF)
      is associated with lung injury in immunocompetent hosts. In this study, we
      investigated the different reactions of lung injury, lung pathology and KGF
      expressions in P. aeruginosa pneumonia between immunosuppressed and
      immunocompetent rats. METHODS: Immunosuppression of male rats was induced by
      injecting immunosuppressive subcutaneously. Pneumonia was established by
      instilling P. aeruginous tracheally. The immunocompetent rats were the control
      group. Survival rate, lung histopathology, pulmonary permeability and oedema, KGF
      mRNA and protein expressions in lungs of both groups were investigated. RESULTS:
      The survival rate of immunosuppressed group was lower than that of
      immunocompetent group (33.3% vs 83.3%). After exposure to bacteria, pulmonary
      permeability and wet/dry ratio in immunosuppressed group were higher than those
      in immunocompetent group. Pulmonary congestion and haemorrhage were more
      intensive in immunosuppressed group compared to immunocompetent group. Apoptosis
      and necrosis were also observed in infected lungs of immunosuppressed rats.
      Although we detected KGF expressions in lungs of both groups after infection, the
      expressions of KGF protein and mRNA gene in immunosuppressed group were much
      lower than in immunocompetent group. CONCLUSIONS: Compared with immunocompetent
      group, there was more intensive lung injury in immunosuppressed group. Severe
      lung injury may contribute to the poor prognosis of pneumonia. KGF expressions of
      pneumonia in immunosuppressed rats were less than those in immunocompetent ones.

PMID- 16989739
TI  - Synaptic dysfunction and oxidative stress in Alzheimer's disease: emerging
      mechanisms.
AB  - In this paper, we review experimental advances in molecular neurobiology of
      Alzheimer's disease (AD), with special emphasis on analysis of neural function of
      proteins involved in AD pathogenesis, their relation with several signaling
      pathways and with oxidative stress in neurons. Molecular genetic studies have
      found that mutations in APP, PS1 and PS2 genes and polymorphisms in APOE gene are
      implicated in AD pathogenesis. Recent studies show that these proteins, in
      addition to its role in beta-amyloid processing, are involved in several
      neuroplasticity-signaling pathways (NMDA-PKA-CREB-BDNF, reelin, wingless, notch,
      among others). Genomic and proteomic studies show early synaptic protein
      alterations in AD brains and animal models. DNA damage caused by oxidative stress
      is not completely repaired in neurons and is accumulated in the genes of synaptic
      proteins. Several functional SNPs in synaptic genes may be interesting candidates
      to explore in AD as genetic correlates of this synaptopathy in a
      "synaptogenomics" approach. Thus, experimental evidence shows that proteins
      implicated in AD pathogenesis have differential roles in several signaling
      pathways related to neuromodulation and neurotransmission in adult and developing
      brain. Genomic and proteomic studies support these results. We suggest that
      oxidative stress effects on DNA and inherited variations in synaptic genes may
      explain in part the synaptic dysfunction seen in AD.

PMID- 16989743
TI  - Immunomodulatory therapy of cytomegalovirus pneumonia after liver
      transplantation.
AB  - BACKGROUND: There has been increasing interest in the research into
      cytomegalovirus (CMV) pneumonia after liver transplantation (LT). This study was
      undertaken to investigate the immunomodulatory therapy of CMV pneumonia after LT.
      METHODS: Six patients with CMV pneumonia after LT from October 2003 to November
      2005 were analyzed retrospectively. They were diagnosed according to clinical
      manifestations, chest X-ray findings and pathogenic changes and given
      comprehensive therapy including mainly immunomodulation therapy and anti-viral
      medication. At the early stage of CMV pneumonia, the dose of immunosuppressive
      agents was decreased or ceased, instead replaced by immunoenhancement therapy.
      During recovery period from CMV pneumonia, the dose of immunosuppressive agents
      was given again or enhanced, and immunoenhancement therapy was ceased. The liver
      function of the patients was monitored closely during the treatment. RESULTS: In
      this series, five patients were survived and one died. The liver function of the
      six patients remained normal during the treatment, and no episode of acute
      rejection took place. CONCLUSIONS: Poor immunity is the pathogenic basis of CMV
      pneumonia after LT. At early stage of CMV pneumonia, the immunity of the patients
      should be enhanced, and during the recovery period from CMV pneumonia,
      immunosuppressants should be given again but immunoenhancement therapy ceased.
      Individualized immunomodulatory therapy is essential to the treatment of CMV
      pneumonia after LT.

PMID- 16989744
TI  - Tissue-targeting lead generation and optimization from random and directed
      screening of technetium-99m labeled tripeptide complex libraries in vivo.
AB  - BACKGROUND: Screening libraries against a molecular target in vitro are idealized
      models that cannot reflect the real state in vivo where biomolecules coexist and
      interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a
      unique noninvasive approach to trace a large number of compounds in vivo.
      METHODS: The C-terminal amide tripeptide libraries were synthesized on Rink Amide
      MBHA resin using iterative and pooling protocol. Technetium (V) oxo core
      [TcO(3+)] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form
      a library of 8000 (99m)Tc tripeptoid complexes. The radiocombinatorial screening
      (RCS) in vivo was carried out on SD rats and A549 tumour bearing mice. RESULTS:
      Signals of tissue distribution and metabolism of libraries were recorded by
      counting or imaging and tissue targeting leads identified by both random and
      directed RCS. Among them, (99m)Tc RPA, (99m)Tc VIG and (99m)Tc RES had specific
      tissue targeting in kidney, liver and tumour respectively. The percent injected
      dose per gram tissue of (99m)Tc labelled leads in their target tissue was highly
      structure dependent. Because the nontarget tissue binding and the metabolism of
      (99m)Tc tripeptoid sublibraries were simultaneously monitored successfully by
      RCS, the interference of background activity was limited to the lowest level.
      Optimization of renal function agent from the labelled libraries was carried out
      by directed screening. (99m)Tc DSG was finally identified the most promising
      agent for renal function studies. CONCLUSIONS: RCS in vivo is a powerful tool for
      the discovery of tissue targeting drugs. The potential screening bias is probably
      the major limitation of labelled libraries.

PMID- 16989745
TI  - Minimally invasive keyhole approaches for removal of tumors of the third
      ventricle.
AB  - BACKGROUND: In recent years, keyhole microsurgery has become an important subject
      of modern minimally invasive neurosurgery. In this study, minimally invasive
      techniques avoiding unnecessary tissue injuries were applied to refine
      traditional approaches for the removal of third ventricular tumors within a
      limited operative filed. METHODS: Individualized keyhole approaches were designed
      according to the characteristics of third ventricular tumors and their growth
      patterns. A series of keyhole approaches such as supraorbital subfrontal
      approach, infratentorial supracerebellar approach, interhemispheric transcallosal
      approach, pterional approach were taken to enter the third ventricle anteriorly,
      posteriorly, superiorly or laterally, respectively. A total of 34 removed tumors
      in or extended into the third ventricle included 11 craniopharyngiomas, 10
      pituitary adenomas, 2 pinealomas, 1 cholesteatoma, 3 germinomas, and 7 gliomas.
      RESULTS: Total tumor resection was done in 27 (79.4%) of the patients, and
      subtotal resection in 7 patients (20.6%). Residual tumor was due to tight
      adherence of germinoma to the vein of Galen (1 patient), craniopharyngioma to the
      pituitary stalk (3), supratentorial extension of pineal region gliomas (1),
      suprasellar extension of gliomas (1) and giant pituitary adenoma (1).
      Complications such as brain contusion, postoperative hemorrhage and infection
      were not associated with keyhole approaches. Extended incision or enlarged bone
      flap was not made because of episode during operation or inadequate exposure.
      CONCLUSIONS: Keyhole approaches are safe, effective and minimally invasive in the
      surgical treatment of tumors deeply seated in the third ventricle. Individualized
      keyhole approach ensures a successful treatment. Tumors in the upper middle part
      of the third ventricle can be exposed by the interhemispheric transcallosal
      keyhole approach. Tumors of the posterior third ventricle may be well exposed by
      the infratentorial supracerebellar keyhole approach. Tumors of the anterior third
      ventricle can be entered by either a supraorbital subfrontal keyhole approach or
      a pterional keyhole approach.

PMID- 16989746
TI  - The antagonism of cholecystokinin octapeptide-8 to the peroxynitrite oxidation on
      a diabetic cataractal rat model.
AB  - BACKGROUND: Cataracts is considered be formed because of an abnormal glucose
      metabolic pathway or oxidative stress. We explored the damaging role of ONOO- and
      antagonism of cholecystokinin octapeptide-8 (CCK-8) in diabetic cataractal rat
      lenses. METHODS: A diabetic cataractal animal model was established by peritoneal
      injection of streptozotocine (STZ). Thirty-six normal SD rats were taken as
      control group; seventy-two were given STZ (45 mg/kg) and then divided into STZ
      group and CCK-8 group (peritoneal injection CCK-8). STZ induced diabetic rats
      were treated with CCK-8 for 60 days. Lenses were examined with slit lamp at 20,
      40 and 60 days. Immunofluorescent staining and Western blot analysis were used
      for determining nitrotyrosine (NT, a marker for ONOO-). PT-PCR and gene array
      analysis were used for determining the expression of inducible nitric oxide
      synthetase mRNA (iNOS mRNA) in lens epithelium (LEC). RESULTS: STZ group rats
      developed lens opacity by 20 days that reached a high level by 60 days after STZ
      injection. CCK-8 group rats delayed the cataract formation. CCK-8 group rats
      delayed the cataract formation. There was no distinct expression of NT and iNOS
      mRNA in control group. In STZ group, there were distinct expression of NT and
      upregulation of iNOS mRNA; however, CCK-8 group showed weak expression of NT and
      downregulation of iNOS mRNA. CONCLUSIONS: NT, which may be a new form of
      oxidative stress, was expressed in diabetic rat LEC although CCK-8 could reverse
      NT damage in LEC. The results suggested that CCK-8 might be a useful therapeutic
      agent against diabetic cataract. The antagonizing mechanism of CCK-8 may be
      related to direct antagonism of ONOO- as well as its inhibition of the expression
      of iNOS mRNA for production of NO and therefore decrease in the formation of ONOO
      .

PMID- 16989747
TI  - Highlight the significance of genetic evolution of H5N1 avian flu.

PMID- 16989748
TI  - Effect of breviscapine on fractalkine expression in chronic hypoxic rats.

PMID- 16989749
TI  - Aberrant p16 promoter hypermethylation in bronchial mucosae as a biomarker for
      the early detection of lung cancer.

PMID- 16989750
TI  - Prevalence of isolated systolic hypertension and analysis on its relative factors
      in 1002 cases over 80 years old in retirement centers for army officers.

PMID- 16989751
TI  - Hypoxic imaging with 99mTc-HL91 single photon emission computed tomography in
      advanced nonsmall cell lung cancer.

PMID- 16989752
TI  - Multiple myeloma with pulmonary embolism: a case report.

PMID- 16989753
TI  - Early detection of Berry syndrome in a newborn with differential cyanosis.

PMID- 16989754
TI  - Successful second transplantation from haploidentical donor for graft failure
      following unrelated cord blood cell transplantation or mismatched related
      transplantation: 2 cases report.

PMID- 16989755
TI  - Rising incidence of pulmonary embolism in modern China.

PMID- 16989756
TI  - Role of human visceral pleura in pleural fluid turnover: need for morphological
      evidence of lymphatic stomata.

PMID- 16989757
TI  - Pattern of mitochondrial DNA variation between and within Anopheles stephensi
      (Diptera: Culicidae) biological forms suggests extensive gene flow.
AB  - Anopheles stephensi Liston is the most prevalent anopheline species and plays an
      important role in malaria transmission in Indian subcontinent and Middle East
      including southern parts of Iran. It exists as three biological forms; "type",
      "intermediate", and variety mysorensis. The type form is reported to be an
      efficient vector of urban malaria, whereas mysorensis and intermediate are
      considered to be rural species and poor vectors. Moreover, differences in
      cuticular hydrocarbon and chromosomal characters have been described between
      urban and rural forms. However, the genetic structure of the biological forms
      remains unclear. This study was conducted to determine the genetic structure of
      the An. stephensi biological forms in south of Iran where all three forms are
      present. Live specimens were collected from the field and transferred to
      insectaries, reared, and identified based on egg morphological characters.
      Genetic structure of the biological forms was studied using PCR-RFLP of 1512 bp
      of mitochondrial DNA (mtDNA) cytochrome oxidase subunit I and II (COI-COII) and
      sequence of about 712 bp of COI and 562 bp of COII genes. Sequence analysis
      showed that except for a few substitutions in COII, all three forms and
      populations were nearly identical. The high homology of COI and COII sequence of
      An. stephensi forms indicates extensive gene flow between populations and forms
      in the region. This data will serve as first report on the sequence of mDNA COI
      COII of biological forms of An. stephensi, which could be used as a diagnostic
      tool to identify vector/non-vector, gene flow, and geographical exchanges.

PMID- 16989758
TI  - Comparison of orbital magnetic resonance imaging in duane syndrome and abducens
      palsy.
AB  - PURPOSE: To help resolve the clinical ambiguity between Duane syndrome with
      severe abduction deficit and abducens palsy, we performed orbital magnetic
      resonance imaging (MRI) to qualify abnormalities of the lateral rectus (LR)
      muscle in these entities. DESIGN: Prospective observational case series. METHODS:
      Orbital MRI was performed in 13 subjects with Duane syndrome (19 eyes), 10
      subjects with chronic abducens palsy (10 eyes), and 10 orthotropic control
      subjects (18 eyes). High-resolution, surface coil, T(1)-weighted MRI was used to
      obtain contiguous, 2-mm thick quasi-coronal images of the orbits in central gaze.
      Digital image analysis was used to quantify cross-sectional area of the
      ipsilesional and contralesional LR to provide comparison with control
      measurements. RESULTS: Mean maximum LR cross-sectional area in Duane syndrome was
      statistically similar to control (P = .454) and contralesional LR cross-sectional
      area (P = .227). However, in chronic abducens palsy, mean maximum ipsilesional LR
      cross-sectional area was markedly smaller than contralesional (P = .003) and
      control cross-sectional areas (P < .0001), as well as smaller than the LR in
      Duane syndrome (P= .0017). CONCLUSIONS: The LR muscle in abducens palsy exhibits
      profound atrophy. The sparing of the LR in Duane syndrome from denervation
      atrophy despite absence of normal abducens innervation suggests existence of
      alternative LR innervation. High-resolution MRI can noninvasively demonstrate LR
      muscle size and distinguish Duane syndrome from chronic abducens palsy in
      uncertain cases.

PMID- 16989759
TI  - Prevalence of age-related maculopathy in the adult population in China: the
      Beijing eye study.
AB  - OBJECTIVE: To evaluate the prevalence of age-related maculopathy (ARM) in adult
      Chinese living in rural or urban regions of mainland China. DESIGN: Population
      based prevalence study. METHODS: The study included 4439 subjects (aged 40 or
      more years) out of 5324 subjects invited to participate (response rate 83.4%). It
      was held in rural and urban regions of Greater Beijing. The participants
      underwent a detailed ophthalmic examination including fundus photography. All
      fundus photographs were graded by the Wisconsin Age-Related Maculopathy Grading
      System. RESULTS: Fundus photographs were available for 4376 (98.6%) subjects.
      Early ARM was present in 122 (1.4%) of 8655 (95% confidence interval [CI] 1.16%
      to 1.66%) eyes or 63 (1.4%) of 4376 (95% CI 1.09% to 1.79%) subjects, late ARM in
      12 (0.14%) of 8655 (95% CI 0.06% to 0.22%) eyes or seven (0.2%) of 4376 (95% CI
      0.04% to 0.28%) subjects, and exudative ARM as part of late ARM in seven (0.1%)
      of 8655 (95% CI 0.02% to 0.14%) eyes or six (0.1%) of 4376 (95% CI 0.03% to
      0.25%) subjects. The prevalence of early ARM, late ARM, and exudative ARM,
      respectively, increased from 0.61%, 0.07%, and 0.07% in the 40-to-44-year age
      group, to 1.66%, 0.26%, and 0.26% in the 55-to-59-year group, and to 2.99%,
      0.90%, and 0.60% in the group aged 75 years and older. ARM was causative for
      visual impairment (best-corrected visual acuity in the better eye, <20/60 and >
      or =20/400) or blindness (visual acuity <20/400) in one subject (0.023%).
      CONCLUSIONS: Visual impairment due to ARM was relatively uncommon in the adult
      Chinese population in rural and urban regions.

PMID- 16989760
TI  - The treatment of congenital dacryocystocele.
AB  - PURPOSE: To determine the proper management of congenital dacryocystocele.
      DESIGN: Retrospective interventional case series. METHODS:  SETTINGS: Clinical
      practice. STUDY POPULATION: Twenty-seven consecutive patients with 29 congenital
      dacryocystoceles who presented from 1987 through 2006. MAIN OUTCOME MEASURES: The
      charts were reviewed for the presence and age of onset of infection, methods and
      age of treatment, and response to treatment. RESULTS: Dacryocystitis and
      preseptal cellulitis requiring intravenous antibiotic therapy were present in 11
      lacrimal systems (37.9%), and dacryocystitis without cellulitis was present in an
      additional 10 lacrimal systems (34.5%). One or more probings were performed in 26
      patients (89.7%). Resolution with conservative therapy occurred in three lacrimal
      systems. The initial probing was successful in seven of seven lacrimal systems
      (100%) that did not have infection, but was successful in only 10 of 19 lacrimal
      systems (53%) that had dacryocystitis with or without cellulitis. The mean age of
      probing in the surgical patients who did not develop infection was 5.9 days,
      whereas the mean age at first probing in surgical patients who developed
      infection was 17.3 days. CONCLUSIONS: Patients with congenital dacryocystocele
      should have probing on an urgent basis and as early in life as possible, unless
      the lacrimal sac decompresses into the nose at the time of the initial
      examination. This approach will reduce the incidence of dacryocystitis and
      cellulitis, and improve the success rate of surgery.

PMID- 16989761
TI  - Immunologic markers, uveitis, and keratoconjunctivitis sicca associated with
      human T-cell lymphotropic virus type 1.
AB  - PURPOSE: To verify the occurrence of keratoconjunctivitis sicca (KCS) and human T
      cell lymphotropic virus type 1 (HTLV-1) associated uveitis (HAU) and to evaluate
      the immunologic status related to HTLV-1. DESIGN: Cross-sectional study. METHODS:
      Ophthalmic examination (both eyes) and immunophenotyping of peripheral blood
      lymphocytes were performed in 207 infected asymptomatic blood donors (AS), 55
      controls (NI), and 55 patients with HTLV-1 associated myelopathy (HAM/TSP).
      Examiner was masked to patient's serologic status. RESULTS: KCS was more frequent
      in HAM/TSP (30/55, 54.5%) than in NI and AS (07/55, 12.7% and 42/207, 20.3%,
      respectively). Presence of lacrimal hyposecretion in KCS individuals was higher
      in the HAM/TSP group (P < .001) as compared with NI and AS. HAU was found in 1/55
      (1.82%) of HAM/TSP patients and 4/207 (1.93%) of HTLV-1 seropositive donors.
      Higher levels of activated CD4(+) and CD8(+) T cells were observed in HAM/TSP.
      Patients with HAU displayed higher percentage of both CD4(+) HLA-DR(+) and
      CD8(+)HLA-DR(+) when compared with NI and AS without HAU. CONCLUSIONS: Patients
      with HAM/TSP manifested more ophthalmologic symptoms than asymptomatic HTLV-1
      infected individuals, with significantly higher KCS and immunologic alterations.
      Levels of activated CD8+ T cells could be used as a prognosis marker of
      inflammatory disease manifestation to follow-up AS individuals.

PMID- 16989762
TI  - Acute endophthalmitis in eyes treated prophylactically with gatifloxacin and
      moxifloxacin.
AB  - PURPOSE: To study the use of prophylactic fourth-generation fluoroquinolone
      antibiotics, gatifloxacin and moxifloxacin, and bacterial sensitivity in cases of
      acute postoperative endophthalmitis following cataract surgery. DESIGN:
      Retrospective, consecutive, observational case series. METHODS: Forty-two eyes of
      42 patients with acute endophthalmitis occurring within six weeks after cataract
      surgery were identified. All patients were seen in a referral vitreoretinal
      practice over a two-year time interval. The number of patients using prophylactic
      gatifloxacin or moxifloxacin and results of bacterial culture and sensitivity to
      all fluoroquinolone antibiotics were recorded. RESULTS: Thirty-one of 42 eyes
      (74%) were treated with perioperative gatifloxacin or moxifloxacin and 24 eyes
      (57%) were continuously taking one of these antibiotics at the time of diagnosis.
      Nineteen eyes (45%) had a positive bacterial culture. The most frequent organism
      isolated was coagulase-negative Staphylococcus. Sensitivities were performed for
      14 gram-positive organisms, and sensitivities to ciprofloxacin (50%), ofloxacin
      (44%), levofloxacin (46%), gatifloxacin (38%), and moxifloxacin (38%) were noted.
      Five organisms were resistant to gatifloxacin and moxifloxacin with a minimum
      inhibitory concentration of 8 microg/ml. All gram-positive organisms were
      sensitive to vancomycin. Median visual acuity improved from hand motions to 20/40
      at last follow-up. CONCLUSION: Acute endophthalmitis can develop after cataract
      surgery despite the prophylactic use of fourth-generation fluoroquinolone
      antibiotics. Gram-positive organisms causing acute endophthalmitis are frequently
      resistant to all fluoroquinolones, including a significant number of cases
      resistant to gatifloxacin and moxifloxacin.

PMID- 16989763
TI  - Ocular surface reconstruction with combination of cultivated autologous oral
      mucosal epithelial transplantation and penetrating keratoplasty.
AB  - PURPOSE: To report an assessment of the two-step surgical combination of
      cultivated autologous oral mucosal epithelial transplantation (COMET) and
      penetrating keratoplasty (PKP) used to treat patients with severe limbal
      deficiency disorders, and to investigate the keratin expression patterns of
      transplanted surviving oral mucosal epithelium. DESIGN: Observational case
      series. METHODS: Two patients with Stevens-Johnson syndrome and chemical eye
      injury were treated by COMET followed, approximately six months later, by a PKP
      triple procedure. In the course of a mean follow-up period of 22.5 months, their
      clinical outcomes and the efficacy of this two-step surgical procedure were
      assessed. In addition, the keratin expression in corneal buttons excised during
      PKP were immunohistochemically examined to characterize the oral mucosal
      epithelium that survived ectopically on the cornea. In vivo laser confocal
      microscopy was used to investigate the structure of the epithelium on the corneal
      grafts. RESULTS: The ocular surfaces were successfully reconstructed with
      cultivated autologous oral mucosal epithelial sheets and PKP. No clinical
      complications, such as persistent epithelial defects, rejections, or recurrence
      of cicatrization, were encountered. Postoperative best-corrected visual acuity
      was 20/125 in one patient and 20/100 in the other. The surviving oral mucosal
      epithelium, distinguished by its fluorescence pattern, consisted of an irregular,
      nonkeratinized, stratified epithelium without goblet cells. Immunohistochemical
      study demonstrated that K3, but not K12, was expressed in the transplanted
      cultivated oral mucosal epithelium that was similar to oral mucosal tissue. In
      vivo, the epithelial structure and cell density in the basal cell layer of the
      corneal grafts were similar to normal cornea. CONCLUSIONS: This study presents a
      two-step surgical approach to treat severely scarred ocular surfaces by means of
      a combination of COMET and PKP. Clinical outcomes suggest that this treatment may
      be beneficial for the maintenance of the reconstructed ocular surface by
      providing oral mucosal epithelium around the corneal graft.

PMID- 16989764
TI  - Cannulation of the suprachoroidal space: a novel drug delivery methodology to the
      posterior segment.
AB  - PURPOSE: To describe, test, and evaluate the pharmacokinetics of a novel
      posterior drug delivery system (PDS) by means of microcannulation of the
      suprachoroidal space in both the primate and pig animal model. DESIGN: Animal
      study. METHODS: A rhesus macaque (Macaca mulatta) (n = 1) and pig model (n = 93)
      were used to evaluate the PDS, a microcannula that combines a drug delivery
      channel with a fiber-optic illumination and optimal transition properties. The
      surgical technique, safety profile, histopathology, retinal and choroidal blood
      flow, injection of tracer dyes, and triamcinolone pharmacokinetics were studied.
      Pre- and postsurgical high-speed video confocal scanning laser ophthalmoscopy
      (cSLO) that used fluorescein and indocyanine green (ICG) imaging and wide-field
      fundus imaging studies were performed. Globes were enucleated for either
      histopathology or pharmacokinetics. RESULTS: Cannulation was performed in 93 of
      94 animals. Complications included: endophthalmitis (1/94), choroidal tear
      (1/94), choroidal blood flow irregularities (4/94), postoperative inflammation
      (6/94), scleral ectasia (4/94), wound abscess (1/94), and others. Histopathology
      demonstrated normal anatomy in uncomplicated cases. Triamcinolone remains in the
      local ocular tissue for at least 120 days, and measurable at very low levels in
      the systemic circulation. CONCLUSIONS: Accessing the suprachoroidal space by the
      microcannulation system can be performed in a safe and reproducible manner by
      using careful surgical technique. Forceful PDS tip impact into connective tissues
      in the macular and optic nerve regions should be avoided. Triamcinolone
      pharmacokinetics are unique and suggest long-term local tissue levels with low
      systemic levels. PDS access to the suprachoroidal space represents a novel drug
      delivery method, applicable to a wide variety of pharmacotherapies to the macula,
      optic nerve, and posterior pole.

PMID- 16989765
TI  - A novel His158Arg mutation in TIMP3 causes a late-onset form of Sorsby fundus
      dystrophy.
AB  - PURPOSE: To describe the phenotype and genotype of a family with suspected Sorsby
      fundus dystrophy (SFD). DESIGN: Case reports and results of deoxyribonucleic acid
      (DNA) analysis. METHODS: Clinical features were determined by complete
      ophthalmologic examination or by review of medical records. Mutational analysis
      of the tissue inhibitor of metalloproteinase (TIMP)3 gene was performed by DNA
      resequencing. Biochemical properties of the mutant TIMP3 protein were studied,
      and phylogenetic and molecular modeling analyses of TIMP proteins were performed.
      RESULTS: Fundi of four affected family members demonstrated active or regressed
      bilateral choroidal neovascularization, whereas another affected individual
      displayed severe diffuse pigmentary degeneration associated with nyctalopia
      characteristic of SFD. Onset of disease occurred in the fifth to seventh decades
      of life. A heterozygous His158Arg mutation was found in seven affected family
      members and was absent from an unaffected member and 98 unrelated controls.
      Bioinformatic analyses indicate that histidine 158 is an evolutionarily conserved
      residue in most vertebrate TIMP homologs and predict that substitution by
      arginine disrupts TIMP3 function. The mutant protein appears to be expressed by
      fibroblasts from an affected family member. Molecular modeling suggests that
      TIMP3 residue 158 may be part of a protein-protein interaction interface.
      CONCLUSION: A novel mutation in TIMP3 causes a late-onset form of SFD in this
      family. His158Arg is the first reported TIMP3 SFD coding sequence mutation that
      does not create an unpaired cysteine. Further study of this unusual mutation may
      provide insight into the mechanism of SFD pathogenesis.

PMID- 16989766
TI  - Development of an open sandwich fluoroimmunoassay based on fluorescence resonance
      energy transfer.
AB  - We have developed a sensitive, one-step, homogeneous open sandwich
      fluoroimmunoassay (OsFIA) based on fluorescence resonance energy transfer (FRET)
      and luminescent semiconductor quantum dots (QDs). In this FRET assay, estrogen
      receptor beta (ER-beta) antigen was incubated with QD-labeled anti-ER-beta
      monoclonal antibody and Alexa Fluor (AF)-labeled anti-ER polyclonal antibody for
      30 min, followed by FRET measurement. The dye separation distance was estimated
      between 80 and 90 A. The current method is rapid, simple, and highly sensitive,
      and it did not require the bound/free reagent separation steps and solid-phase
      carriers. A concentration as low as 0.05 nM (2.65 ng/ml) receptor was detected
      with linearity. In addition, the assay was performed with commercial antibodies.
      This assay provides a convenient alternative to conventional, laborious sandwich
      immunoassays.

PMID- 16989767
TI  - Development of an analytical method for genome-wide functional identification of
      plant acyl-coenzyme A-dependent acyltransferases.

PMID- 16989768
TI  - Occupational health problems and injuries among Quebec's physical educators.
AB  - The purpose of this study was to describe the traumatology of teaching physical
      education (PE) and to document the causes and mechanisms of injuries in this
      occupation. Our sample was composed of 314 physical educators (PEs) teaching at
      three school levels (primary school, secondary school and college) who responded
      to a questionnaire survey. The results showed a 0.55 rate of recent lesion per
      teacher per year (0.65 for women and 0.51 for men). A total of 37.6% of subjects
      were affected by a lesion during the last year at work. Subjects with a higher
      weekly frequency of leisure physical activities or endurance activities (five
      times and more) were less affected by chronic lesions as well as those who
      frequently practiced aerobic physical activities. Prevalence of chronic injuries
      was higher in older teachers. Our results confirm that the rate of lesions in
      this group of workers is high, and that school level and respondent age may
      influence the rate of lesion and the characteristics of risk factors. In
      particular, the effect of ageing and teaching specialization on the incidence of
      occupational problems in PEs warrants further research. Given the relatively high
      rate of injuries among PE teachers, we suggest that it is necessary to further
      explore preventive strategies to reduce occupational risk in these workers. In
      particular, prophylactic physical activity outside of work may represent such a
      strategy since PEs more active outside their work have lower chronic injury
      prevalence. PEs gave long periods of standing the highest rating for movements or
      positions most likely to cause them occupational injuries. It can thus be
      suggested to find ways to reduce standing position sustained for long periods.

PMID- 16989769
TI  - Bidirectional electron transfer in photosystem I: replacement of the symmetry
      breaking tryptophan close to the PsaB-bound phylloquinone A1B with a glycine
      residue alters the redox properties of A1B and blocks forward electron transfer
      at cryogenic temperatures.
AB  - A conserved tryptophan residue located between the A(1B) and F(X) redox centres
      on the PsaB side of the Photosystem I reaction centre has been mutated to a
      glycine in Chlamydomonas reinhardtii, thereby matching the conserved residue
      found in the equivalent position on the PsaA side. This mutant (PsaB:W669G) was
      studied using EPR spectroscopy with a view to understanding the molecular basis
      of the reported kinetic differences in forward electron transfer from the A(1A)
      and the A(1B) phyllo(semi)quinones. The kinetics of A(1)(-) reoxidation due to
      forward electron transfer or charge recombination were measured by electron spin
      echo spectroscopy at 265 K and 100 K, respectively. At 265 K, the reoxidation
      kinetics are considerably lengthened in the mutant in comparison to the wild
      type. Under conditions in which F(X) is initially oxidised the kinetics of charge
      recombination at 100 K are found to be biphasic in the mutant while they are
      substantially monophasic in the wild-type. Pre-reduction of F(X) leads to
      biphasic kinetics in the wild-type, but does not alter the already biphasic
      kinetic properties of the PsaB:W669G mutant. Reduction of the [4Fe-4S] clusters
      F(A) and F(B) by illumination at 15 K is suppressed in the mutant. The results
      provide further support for the bi-directional model of electron transfer in
      Photosystem I of C. reinhardtii, and indicate that the replacement of the
      tryptophan residue with glycine mainly affects the redox properties of the PsaB
      bound phylloquinone A(1B).

PMID- 16989770
TI  - An HPLC-based method of estimation of the total redox state of plastoquinone in
      chloroplasts, the size of the photochemically active plastoquinone-pool and its
      redox state in thylakoids of Arabidopsis.
AB  - We have described a direct, high-performance liquid chromatography-based method
      of estimation of the total level of plastoquinone (PQ) in leaves, the redox state
      of total (photoactive and non-photoactive) PQ, as well as the redox state of the
      PQ-pool that is applicable to any illumination conditions. This method was
      applied to Arabidopsis thaliana leaves but it can be applied to any other plant
      species. The obtained results show that the level of total PQ was 25+/-3
      molecules/1000 chlorophyll (Chl) molecules in relation to foliar total Chl
      content. The level of the photoactive PQ, i.e., the PQ-pool, was about 31% of the
      total PQ present in Arabidopsis leaves that corresponds to about 8 PQ
      molecules/1000 Chl molecules. The reduction level of the non-photoactive PQ
      fraction, present outside thylakoids in chloroplasts, was estimated to account
      for about 49%. The measurements of the redox state of the PQ-pool showed that the
      pool was reduced during the dark period in about 24%, and during the light period
      (150 micromol/m(2).s) the reduction of the PQ-pool increased to nearly 100%. The
      obtained results were discussed in terms of the activity of chlororespiration
      pathways in Arabidopsis and the regulatory role of the redox state of PQ-pool in
      various physiological and molecular processes in plants.

PMID- 16989771
TI  - Insertion selectivity of antimicrobial peptide protegrin-1 into lipid monolayers:
      effect of head group electrostatics and tail group packing.
AB  - The ability to selectively target the harmful microbial membrane over that of the
      host cell is one of the most important characteristics of the antimicrobial
      peptides (AMPs). This selectivity strongly depends on the chemical and structural
      properties of the lipids that make up the cell membrane. A systematic study of
      the initial membrane selectivity of protegrin-1 (PG-1), a beta-sheet AMP, was
      performed using Langmuir monolayers. Constant pressure insertion assay was used
      to quantify the amount of PG-1 insertion and fluorescence microscopy was employed
      to observe the effect of PG-1 on lipid ordering. Charge and packing properties of
      the monolayer were altered by using lipids with different head groups,
      substituting saturated with unsaturated lipid tail group(s) and incorporating
      spacer molecules. PG-1 inserted most readily into anionic films composed of
      phosphatidylglycerol (PG) and lipid A, consistent with its high selectivity for
      microbial membranes. It also discriminated between zwitteranionic phospholipids,
      inserting more readily into phosphatidylcholine (PC) monolayers than those
      composed of phosphatidylethanolamine, potentially explaining why PG-1 is
      hemolytic for PC-rich human erythrocytes and not for the PE-rich erythrocytes of
      ruminants. Increased packing density of the monolayer by increased surface
      pressure, increased tail group saturation or incorporation of dihydrocholesterol
      diminishes the insertion of PG-1. Fluorescence microscopy shows that lipid
      packing is disordered upon PG-1 insertion. However, the presence of PG-1 can
      still affect lipid morphology even with no observed PG-1 insertion. These results
      show the important role that lipid composition of the cell membrane plays in the
      activity of AMPs.

PMID- 16989773
TI  - Rollercoaster asthma: when positive emotional stress interferes with dyspnea
      perception.
AB  - The current study assessed how negative and positive stress is related to dyspnea
      perception. The participants were 25 young women with a medical diagnosis of
      severe asthma, and 15 matched controls. Stress was induced during repeated
      rollercoaster rides. Results showed that negative emotional stress and blood
      pressure peaked just before, and positive emotional stress and heart beat peaked
      immediately after rollercoaster rides. Dyspnea in women with asthma was higher
      just before than immediately after rollercoaster rides, even in women with asthma
      with a rollercoaster-evoked reduction in lung function. These results suggest
      that stressed and highly aroused individuals with chronic asthma tend to perceive
      dyspnea in terms of acquired, familiar associations between dyspnea and positive
      versus negative feeling states, favoring either underperception or overperception
      of dyspnea, depending on the emotional valence of a situation.

PMID- 16989772
TI  - Production in Escherichia coli of a recombinant C-terminal truncated precursor of
      surfactant protein B (rproSP-B Delta C). Structure and interaction with lipid
      interfaces.
AB  - SP-B, a protein absolutely required to maintain the lungs open after birth, is
      synthesized in the pneumocytes as a precursor containing C-terminal and N
      terminal domains flanking the mature sequence. These flanking-domains are cleaved
      to produce mature SP-B, coupled with its assembly into pulmonary surfactant lipid
      protein complexes. In the present work we have optimized over-expression in
      Escherichia coli and purification of rproSP-B(DeltaC), a recombinant form of
      human proSP-B lacking the C-terminal flanking peptide, which is still competent
      to restore SP-B function in vivo. rProSP-B(DeltaC) has been solubilized, purified
      and refolded from bacterial inclusion bodies in amounts of about 4 mg per L of
      culture. Electrophoretic mobility, immunoreactivity, N-terminal sequencing and
      peptide fingerprinting all confirmed that the purified protein had the expected
      mass and sequence. Once refolded, the protein was soluble in aqueous buffers.
      Circular dichroism and fluorescence emission spectra of bacterial rproSP
      B(DeltaC) indicated that the protein is properly folded, showing around 32% alpha
      helix and a mainly hydrophobic environment of its tryptophan residues. Presence
      of zwitterionic or anionic phospholipids vesicles caused changes in the
      fluorescence emission properties of rproSP-B(DeltaC) that were indicative of
      lipid-protein interaction. The association of this SP-B precursor with membranes
      suggests an intrinsic amphipathic character of the protein, which spontaneously
      adsorbs at air-liquid interfaces either in the absence or in the presence of
      phospholipids. The analysis of the structure and properties of recombinant proSP
      B(DeltaC) in surfactant-relevant environments will open new perspectives on the
      investigation of the mechanisms of lipid and protein assembly in surfactant
      complexes.

PMID- 16989774
TI  - VCC-1, a novel chemokine, promotes tumor growth.
AB  - We have identified a novel human gene by transcriptional microarray analysis,
      which is co-regulated in tumors and angiogenesis model systems with VEGF
      expression. Isolation of cDNA clones containing the full-length VCC-1 transcript
      from both human and mouse shows a 119 amino acid protein with a 22 amino acid
      cleavable signal sequence in both species. Comparison of the protein product of
      this gene with hidden Markov models of all known proteins shows weak but
      significant homology with two known chemokines, SCYA17 and SCYA16. Northern
      analysis of human tissues detects a 1 kb band in lung and skeletal muscle. Murine
      VCC-1 expression can also be detected in lung as well as thyroid, submaxillary
      gland, epididymis, and uterus tissues by slot blot analysis. By quantitative real
      time RT-PCR 71% of breast tumors showed 3- to 24-fold up-regulation of VCC-1. In
      situ hybridization of breast carcinomas showed strong expression of the gene in
      both normal and transformed mammary gland ductal epithelial cells. In vitro,
      human microvascular endothelial cells grown on fibronectin increase VCC-1
      expression by almost 100-fold. In addition, in the mouse angioma endothelial cell
      line PY4.1 the gene was over-expressed by 28-fold 6 h after induction of tube
      formation while quiescent and proliferating cells showed no change. VCC-1
      expression is also increased by VEGF and FGF treatment, about 6- and 5-fold,
      respectively. Finally, 100% of mice injected with NIH3T3 cells over-expressing
      VCC-1 develop rapidly progressing tumors within 21 days while no growth is seen
      in any control mice injected with NIH3T3 cells containing the vector alone. These
      results strongly suggest that VCC-1 plays a role in angiogenesis and possibly in
      the development of tumors in some tissue types.

PMID- 16989775
TI  - Expression of mouse Fbxw7 isoforms is regulated in a cell cycle- or p53-dependent
      manner.
AB  - Fbxw7 is the F-box protein component of an SCF-type ubiquitin ligase that
      contributes to the ubiquitin-dependent degradation of cell cycle activators and
      oncoproteins. Three isoforms (alpha, beta, and gamma) of Fbxw7 are produced from
      mRNAs with distinct 5' exons. We have now investigated regulation of Fbxw7
      expression in mouse tissues. Fbxw7alpha mRNA was present in all tissues examined,
      whereas Fbxw7beta mRNA was detected only in brain and testis, and Fbxw7gamma mRNA
      in heart and skeletal muscle. The amount of Fbxw7alpha mRNA was high during
      quiescence (G0 phase) in mouse embryonic fibroblasts (MEFs) and T cells, but it
      decreased markedly as these cells entered the cell cycle. The abundance of
      Fbxw7alpha mRNA was unaffected by cell irradiation or p53 status. In contrast, X
      irradiation increased the amount of Fbxw7beta mRNA in wild-type MEFs but not in
      those from p53-deficient mice, suggesting that radiation-induced up-regulation of
      p53 leads to production of Fbxw7beta mRNA. Our results thus indicate that
      expression of Fbxw7 isoforms is differentially regulated in a cell cycle- or p53
      dependent manner.

PMID- 16989776
TI  - Parafibromin inhibits cancer cell growth and causes G1 phase arrest.
AB  - The HRPT2 (hereditary hyperparathyroidism type 2) tumor suppressor gene encodes a
      ubiquitously expressed 531 amino acid protein termed parafibromin. Inactivation
      of parafibromin predisposes one to the development of HPT-JT syndrome. To date,
      the role of parafibromin in tumorigenesis is largely unknown. Here, we report
      that parafibromin is a nuclear protein that possesses anti-proliferative
      properties. We show that overexpression of parafibromin inhibits colony formation
      and cellular proliferation, and induces cell cycle arrest in the G1 phase.
      Moreover, HPT-JT syndrome-derived mutations in HRPT2 behave in a dominant
      negative manner by abolishing the ability of parafibromin to suppress cell
      proliferation. These findings suggest that parafibromin has a critical role in
      cell growth, and mutations in HRPT2 can directly inhibit this role.

PMID- 16989777
TI  - Radiocontrast media cause dephosphorylation of Akt and downstream signaling
      targets in human renal proximal tubular cells.
AB  - Radiocontrast medium induced nephrotoxicity is a major clinical problem. There is
      considerable interest in reducing the incidence of acute renal failure due to the
      use of radiocontrast media (RCM). Reduction of renal blood flow and direct toxic
      effect on renal tubular epithelial cells have been postulated as major causes of
      RCM nephropathy. Understanding the molecular mechanisms by which RCM cause cell
      damage may allow the development of pharmacological therapy to prevent their
      nephrotoxicity. In this work we have investigated the signaling pathways that may
      be affected by RCM. The incubation of human renal tubular proximal cells with
      sodium diatrizoate, iopromide and iomeprol caused a marked dephosphorylation of
      the kinase Akt on Ser473 within 5min of incubation. RCM also caused a decrease in
      cell viability, which was substantially alleviated by transfecting the cells with
      a constitutively active form of Akt. Further downstream targets of Akt, including
      the Forkhead family of transcription factors FKHR and FKHRL1, were also
      dephosphorylated by RCM at Thr24 and Thr32, respectively. The P70S6 kinase was
      also dephosphorylated at Thr389 and Ser371 by RCM. However there was a more
      dramatic decrease in phosphorylation of the phosphorylated form of mammalian
      target of rapamycin (mTOR) and of the extracellular-signal regulated kinases
      (ERK) 1/2 caused by sodium diatrizoate than by iopromide. These results
      demonstrate the effect of RCM on some intracellular signaling pathways that may
      allow understanding of the mechanism of their toxicity and may allow the
      development of strategies to overcome their adverse effects.

PMID- 16989778
TI  - Successful antidepressant therapy restores the disturbed interplay between TNF
      alpha system and HPA axis.
AB  - BACKGROUND: In depressed patients, alterations in the hypothalamo-pituitary
      adrenocortical (HPA) system are the most consistent neurobiological finding. HPA
      axis activity and cytokines are intrinsically intertwined: inflammatory cytokines
      stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion, while, in
      turn, glucocorticoids suppress the synthesis of proinflammatory cytokines.
      METHODS: We examined alterations in plasma levels of tumor necrosis factor-alpha
      (TNF-alpha), levels of its soluble receptors p55 (sTNF-R p55) and p75 (sTNF-R
      p75) as well as changes in the HPA system function using the combined
      dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at
      discharge in 70 depressed inpatients without inflammation. RESULTS: On admission,
      TNF-alpha levels were inversely associated with the ACTH response to the combined
      dex/CRH test. Changes in TNF-alpha, sTNF-R p55, and sTNF-R p75 plasma levels from
      admission to discharge were positively correlated with the dex/CRH test outcome
      at discharge. Subgroup analysis revealed that this association was restricted to
      those patients achieving remission. In this subgroup, TNF-alpha levels at
      discharge were also positively correlated with dex/CRH test response at
      discharge. CONCLUSIONS: Our results suggest that elevated HPA axis activity in
      acute depression suppresses TNF-alpha system activity, while after remission,
      when HPA axis activity has normalized, the TNF-alpha system seems to gain
      influence on the HPA system.

PMID- 16989780
TI  - Misunderstandings about how to choose a reference region.

PMID- 16989781
TI  - Vagal afferent neurons projecting to the stomach and small intestine exhibit
      multiple N-methyl-D-aspartate receptor subunit phenotypes.
AB  - Previous reports suggest that NMDA receptors participate in control of food
      intake via vagal afferent neurons that innervate the upper gastrointestinal (GI)
      tract. While messenger RNA coding for the NR1 NMDA receptor subunit is present in
      a majority of vagal afferent neurons of nodose ganglia (NG), immunoreactivity for
      other NMDA receptor subunits (NR2B, NR2C and NR2D) are expressed in more limited
      subpopulations of vagal afferents. To determine whether vagal afferent neurons
      that project to the stomach or duodenum exhibit distinct NMDA receptor subunit
      phenotypes, we examined immunoreactivity (IR) for NMDA receptor NR1, NR2B, NR2C
      and NR2D subunits in NG neurons that were labeled by injections of the retrograde
      tracer Fast Blue (FB) into the wall of the stomach or duodenum. FB injections
      into the fundus or corpus of the stomach labeled comparable numbers of neurons in
      both the left and right NG, while proximal duodenal injections labeled only
      neurons of left NG. NR1-IR expression was observed in most neurons innervating
      the upper GI tract (fundus, 97%; corpus, 95%; duodenum, 98%). Likewise, most
      neurons that innervated the upper GI tract expressed NR2B-IR (fundus, 98%;
      corpus, 85%; duodenum, 81%). NR2C-IR was observed in only 52%, 46% and 32% of FB
      positive neurons projecting to the fundus, corpus or duodenum respectively, while
      NR2D-IR occurred in an even more restricted FB-labeled subpopulation (fundus,
      13%; corpus, 26%; and duodenum, 18%). Our observations indicate that different
      subpopulations of vagal afferents express distinct NMDA receptor subunit
      phenotypes. However, the neuronal distribution of NMDA receptor subunits is not
      correlated with innervation of either the stomach or duodenum.

PMID- 16989782
TI  - Effects of memory load on cortical oscillatory activity during auditory pattern
      working memory.
AB  - The present magnetoencephalography study investigated memory load-dependent
      changes in cortical oscillatory activity during a modified auditory version of
      the Sternberg paradigm. Twelve subjects were presented with test stimulus sets of
      1-3 syllables spoken in a natural female voice. After an 800-ms delay period, a
      probe syllable was presented and subjects had to judge whether the probe had been
      included in the preceding test set. Compared to a non-memory-control task, memory
      trials elicited an increase of beta activity over right temporal regions and an
      increase of alpha activity over right middle prefrontal cortex at the end of the
      delay phase. Monotonic increases in spectral amplitude as a function of memory
      load were revealed for the beta band over right temporal sensors and the alpha
      band over right frontal sensors during the delay period. The results demonstrate
      the relevance of both beta and alpha oscillations for the memorization of
      multiple stimuli. The former may be associated with the representation of task
      relevant stimulus features, while the latter may reflect the top-down control of
      these representations.

PMID- 16989783
TI  - Acute restraint increases NADPH-diaphorase staining in distinct subregions of the
      rat dorsal raphe nucleus: implications for raphe serotonergic and nitrergic
      transmission.
AB  - The brainstem dorsal raphe nucleus (DRN) maintains a rough topographic cell
      ordering with respect to biological function. This study examined the influence
      of acute restraint on nitric oxide (NO) synthase (NOS) neurons in distinct DRN
      subregions. NADPH diaphorase staining (NOS index) intensity was higher in the DRN
      dorsomedial, ventromedial and lateral wings subregions of restrained vs. control
      rats. The mean number of cells was not significantly different between both
      groups of animals. The restrained-induced NADPH-diaphorase activity was
      significantly higher in the rostral ventromedial and caudal lateral wings than
      the corresponding caudal and rostral subregions but no significant difference was
      observed between rostral and caudal dorsomedial subregions. These observations
      suggest that restraint stress differentially activates NO-producing neurons in
      distinct DRN subregions.

PMID- 16989784
TI  - Nonlinear analysis of discharge patterns in monkey basal ganglia.
AB  - Spontaneous discharge of basal ganglia neurons is often analyzed with time- or
      frequency-domain methods. However, it has been shown that sequences of inter
      spike interval series are not fully described by such linear procedures. We
      therefore carried out a characterization of the nonlinear features of spontaneous
      discharge of neurons in the primate basal ganglia. We studied the spontaneous
      activity of neurons in the subthalamic nucleus (22 cells), as well as neurons in
      the external and internal pallidal segments (53 and 39 cells, respectively),
      recorded with standard extracellular recording methods in two awake Rhesus
      monkeys. As a measure of the statistical irregularity of neuronal discharge, we
      compared the approximate entropy of inter-spike interval sequences with that of
      shuffled representations of the same data. In all three basal ganglia structures,
      approximately 95% of the original data showed lower approximate entropy values
      than the shuffled data, suggesting a temporal organization in the original
      sequence. Fano factor analysis confirmed the presence of a temporal organization
      of inter-spike interval sequences, and indicated the presence of self-similarity
      in the great majority of them. In addition, Hurst exponent analysis showed that
      the inter-spike interval series are persistent. Hurst exponents often differ
      between short and long scaling ranges. Subsequent principal component analyses
      allowed us to identify three distinct patterns of the temporal evolution of inter
      spike interval sequences in the phase space. These types were found in varying
      distributions in all three nuclei. Our analyses demonstrate that the discharge of
      most neurons in the basal ganglia of awake monkeys has nonlinear features that
      may be important for information coding in the basal ganglia.

PMID- 16989785
TI  - The effect of chronic lorazepam administration in aging mice.
AB  - To assess benzodiazepine tolerance in aged animals, lorazepam or vehicle was
      administered chronically to male Crl: CD-1(ICR)BR mice. Pharmacodynamic and
      neurochemical endpoints were examined on days 1 and 14 of drug administration.
      There was no age-related significant difference in plasma lorazepam levels. Young
      and middle-aged animals demonstrated behavioral tolerance to lorazepam, while the
      aged animals showed a similar trend which failed to reach significance. In
      addition, aged animals also showed a trend toward tolerance to the anticonvulsant
      effects of lorazepam. There were no changes in alpha1 mRNA levels in cortex or
      hippocampus following administration of lorazepam when compared to vehicle
      treated animals in any age group. Aged animals, however, had an initial increase
      in alpha1 mRNA expression in cortex and hippocampus on day 1 of vehicle treatment
      followed by decreased expression on day 14. These age-related changes were
      abolished by lorazepam administration. In summary, age-related sensitivity to the
      effects of lorazepam was not demonstrated in the present study. However,
      comparison of these data to other studies indicates that the effect of chronic
      benzodiazepine treatment may be specific to the benzodiazepine administered, the
      technique used to quantify mRNA expression changes, the subunits of the GABA(A)
      receptor investigated and the brain region analyzed. The phenomenon of
      benzodiazepine sensitivity in the elderly is an area of research which remains
      controversial and may well be compound specific. Determining benzodiazepines that
      do not produce pharmacodynamic sensitivity, such as lorazepam, may allow more
      careful prescribing and dosing of these drugs, and perhaps even the development
      of specific agents which could avoid this sensitivity.

PMID- 16989786
TI  - Transcriptional profiling of depolarization-dependent phenotypic alterations in
      primary cultures of developing granule neurons.
AB  - Rat cerebellar granule neurons cultured in medium supplemented with elevated KCl
      are extensively used as a model to examine the coupling between neural activity
      and Ca(2+)-dependent gene expression. Elevated (25 mM) KCl is believed to mimic
      endogenous neural activity because it promotes depolarization and Ca(+2)
      dependent survival and some aspects of maturation. By comparison, at least half
      of the granule neurons grown in standard medium containing 5 mM KCl undergo
      apoptosis beginning approximately 4 days in vitro. However, accumulating evidence
      suggests that chronic depolarization induces phenotypic abnormalities whereas
      growth in chemically defined medium containing 5 mM KCl more closely resembles
      the constitutive phenotype. To examine this, oligonucleotide microarrays and RT
      PCR of selected mRNAs were used to compare transcription profiles of cultures
      grown in 5 mM and 25 mM KCl. In some cases, N-methyl-D-aspartate (NMDA) which,
      like elevated KCl, promotes long-term survival was also tested. Robust changes in
      several gene groups were observed and indicated that growth in elevated KCl:
      induces expression of mRNAs that are not normally observed; represses expression
      of mRNAs that should be present; maintains expression of mRNAs that are markers
      of immature neurons. Supplementation of the growth medium with NMDA instead of
      elevated KCl produces similar abnormalities. Altogether, these data indicate that
      growth in 5 mM KCl more closely mimics survival and maturation of granule neurons
      in vivo and should therefore be adopted in future studies.

PMID- 16989787
TI  - Hemispheric asymmetries in font-specific and abstractive priming of written
      personal names: Evidence from event-related brain potentials.
AB  - We assessed hemispheric differences in font-specific and abstractive repetition
      priming for famous persons' names. Participants performed speeded familiarity
      judgments for foveally presented famous and unfamiliar names. Famous target names
      were preceded by primes (150 ms) in the left or right visual field (LVF or RVF).
      Primes were either the same name as the target written in the same font (font
      specific priming), the same name in a different font (abstractive priming), or a
      different name (unprimed condition). In reaction times, LH superiority was strong
      for abstractive priming across fonts, but was reduced to insignificance for font
      specific priming. We observed 3 different ERP modulations of priming for target
      names: a small font-specific posterior N200 (160-220 ms), a left temporal N250r
      (220-300 ms), and an N400 modulation (300-500 ms). The left temporal N250r
      exhibited large and abstractive priming for RVF primes, but smaller and font
      specific priming for LVF primes. N400 effects were observed in all priming
      conditions. With respect to previous findings that N200, N250r, and N400 reflect
      facilitation at the levels of font-specific encoding, lexical entries for names,
      and semantic processing, respectively, these findings suggest that the LH
      superiority for name processing is particularly pronounced for the access to
      abstractive lexical entries for written names, a process that may be mediated by
      the left fusiform cortex.

PMID- 16989788
TI  - Effect of treatment with choline alphoscerate on hippocampus microanatomy and
      glial reaction in spontaneously hypertensive rats.
AB  - The influence of long term treatment with choline alphoscerate on microanatomy of
      hippocampus and glial reaction was assessed in spontaneously hypertensive rats
      (SHR) used as an animal model of cerebrovascular disease. Choline alphoscerate is
      a cholinergic precursor, which has shown to be effective in countering cognitive
      symptoms in forms of dementia disorders of degenerative, vascular or combined
      origin. Male spontaneously hypertensive rats (SHR) aged 6 months and age-matched
      normotensive Wistar-Kyoto (WKY) rats were treated for 8 weeks with an oral daily
      dose of 100 mg/kg of choline alphoscerate, 285 mg/kg of phosphatidylcholine
      (lecithin) or vehicle. On the hippocampus of different animal groups, nerve cell
      number and GFAP-immunoreactive astrocytes were assessed by neuroanatomical,
      immunochemical and immunohistochemical techniques associated with quantitative
      analysis. Treatment with choline alphoscerate countered nerve cell loss and glial
      reaction primarily in the CA1 subfields and in the dentate gyrus of the
      hippocampus of SHR. Phosphatidylcholine did not affect hypertension-dependent
      changes in hippocampal microanatomy. Both compounds did not affect blood pressure
      values in SHR. These data suggest that choline alphoscerate may play a role in
      the countering hippocampal changes induced by cerebrovascular involvement. The
      observation that treatment with choline alphoscerate attenuates the extent of
      glial reaction in the hippocampus of SHR suggests also that the compound may
      afford neuroprotection in this animal model of vascular brain damage.

PMID- 16989789
TI  - Chlorodifluoromethyl-substituted monosaccharide derivatives--radical activation
      of the carbon-chlorine-bond.
AB  - The dithionite-mediated addition of BrCF(2)Cl to 3,4-di-O-pivaloyl-D-xylal (1)
      generated preferably 1-CF(2)Cl-substituted products, that is, (2-bromo-2-deoxy
      3,4-di-O-pivaloyl-beta-D-xylopyranosyl)-chlorodifluoromethane and (2-deoxy-3,4-di
      O-pivaloyl-beta-D-threo-pentopyranosyl)-chlorodifluoromethane. Selected
      chlorodifluoromethyl-substituted monosaccharide derivatives were
      hydrodechlorinated or alkylated at the CF(2)Cl-group using tin reagents under
      radical reaction conditions. Thus, hydrodechlorinations of (2,3,4-tri-O-acetyl-6
      deoxy-alpha-L-galactopyranosyl)-chlorodifluoromethane and of methyl 3,4-di-O
      acetyl-2-C-chlorodifluoromethyl-2,6-dideoxy-alpha/beta-L-glucopyranoside are
      reported using tri-n-butyltin hydride initiated by AIBN. UV-initiated allylations
      are reported for reactions of (2-deoxy-3,4-di-O-pivaloyl-beta-D-threo
      pentopyranosyl)-chlorodifluoromethane, (2,3,4-tri-O-acetyl-6-deoxy-alpha-L
      galactopyranosyl)-chlorodifluoromethane, 1,3,4,6-tetra-O-acetyl-2-C
      chlorodifluoromethyl-2-deoxy-alpha-D-glucopyranose, 1,3,4,6-tetra-O-acetyl-2-C
      chlorodifluoromethyl-2-deoxy-alpha-D-mannopyranose and methyl 3,4-di-O-acetyl-2-C
      chlorodifluoromethyl-2-deoxy-alpha/beta-D-rabinopyranoside with allyltri-n
      butyltin.

PMID- 16989790
TI  - Asymmetric organocatalysis with glycosyl-beta-amino acids: direct asymmetric
      aldol reaction of acetone with aldehydes.
AB  - Direct asymmetric aldol reaction of acetone with aromatic aldehydes was achieved
      in good yields and high enantioselectivity using 5-amino-5-deoxy-beta-L-ido
      (alpha-D-gluco)-heptofuranuronic acids as a new class of organocatalysts.

PMID- 16989791
TI  - Potential sialyltransferase inhibitors based on neuraminyl substitution by
      hetaryl rings.
AB  - Replacement of the neuraminyl residue by a wide range of aryl rings in transition
      state analogs of CMP-Neu5Ac led to readily accessible and potent inhibitors of
      alpha-(2-->6)- and alpha-(2-->3)-sialyltransferases. The synthesis of a series of
      potential sialyltransferase inhibitors in which the neuraminyl residue is
      replaced by hetaryl methylphosphonate residues (thiazole, benzothiazole,
      benzoxazole, benzothiophene and thiophene) is described in this paper.

PMID- 16989792
TI  - Carotid arterial stiffness, elastic fibre network and vasoreactivity in
      semicarbazide-sensitive amine-oxidase null mouse.
AB  - OBJECTIVE: We examined the arterial phenotype of semicarbazide-sensitive amine
      oxidase null mouse (SSAO -/-) using various techniques including high resolution
      echotracking. METHODS AND RESULTS: SSAO -/- mice showed no change in arterial
      pressure under anesthesia. The in vivo arterial diameter, only measured in the
      carotid artery (CA), was higher in SSAO -/- than in SSAO +/+ animals. Elastic
      modulus-wall stress curves and CA rupture pressure were similar between SSAO -/-
      and +/+ mice, indicating no change in arterial wall stiffness or mechanical
      strength. There was no significant difference in insoluble elastin, total
      collagen content and elastic lamellar morphology between the two genotypes. No
      alteration in vascular reactivity was observed in aortic rings and mesenteric
      arteries from SSAO -/- mice. Aortic lysyl oxidase (LO) activity remained
      unaltered, indicating that SSAO invalidation is not accompanied by a compensatory
      increase in LO activity. CONCLUSION: This is the first functional study of
      arteries lacking SSAO. Our results indicate that SSAO -/- mice present an
      increased arterial diameter associated with normal arterial mechanical
      properties, suggesting that SSAO deficiency might contribute to arterial wall
      remodeling. However, these results argue against the hypothesis that SSAO
      intervenes in elastic fibre organization, elastin cross-linking processes and
      vasoreactivity.

PMID- 16989793
TI  - Extended atrial conduction system characterised by the expression of the HCN4
      channel and connexin45.
AB  - OBJECTIVE: In the heart, there are multiple supraventricular pacemakers involved
      in normal pacemaking as well as arrhythmias and the objective was to determine
      the distribution of HCN4 (major isoform underlying the pacemaker current, I(f))
      in the atria. METHODS: In the atria of the rat, the localisation of HCN4 and
      connexins was determined using immunohistochemistry, and electrical activity was
      recorded using extracellular electrodes. RESULTS: As expected, HCN4 and Cx45 (but
      not Cx43) were expressed in the sinoatrial node extending from the superior vena
      cava down the crista terminalis. The same pattern of expression of HCN4 and
      connexins was observed in a novel tract of nodal-like cells extending from the
      superior vena cava down the interatrial groove. Although the sinoatrial node was
      usually the leading pacemaker site, the novel tract of HCN4-expressing cells was
      capable of pacemaking and could act as the leading pacemaker site; there was
      evidence of a hierarchy of pacemakers. The same pattern of expression of HCN4 and
      connexins was also observed in the atrioventricular ring bundle (including the
      atrioventricular node) encircling the tricuspid valve, but not in the
      atrioventricular ring bundle encircling the mitral valve. HCN4 was not expressed
      in the pulmonary veins. CONCLUSIONS: The widespread distribution of HCN4 can
      explain the widespread location of the leading pacemaker site during sinus
      rhythm, the extensive region of tissue that has to be ablated to stop sinus
      rhythm, and the widespread distribution of ectopic foci responsible for atrial
      tachycardia.

PMID- 16989794
TI  - Chemical process-based reconstruction of exposures for an epidemiological study.
      Part II. Estimated exposures to chloroprene and vinyl chloride.
AB  - In a four-facility occupational epidemiology study of chloroprene monomer and
      polymer production workers, the chloroprene (CD) and vinyl chloride monomer (VCM)
      exposures were modeled for plant specific job title classes. In two facilities an
      acetylene-based process was used and in the other two plants only a butadiene
      based process was used in the monomer synthesis. In the Acetylene process VCM was
      an undesirable by-product to be removed. In the newer butadiene-based process,
      VCM was not involved and the exposures to CD were considerably lower than they
      were in the earlier years. One of the limiting factors was the operator rotation
      within a number of job titles. This rotation and inability to differentiate
      between job titles subsumed in job classifications recorded in the work histories
      required an exposure classification scheme based on an order of magnitude
      separation of exposure classes. In the four facilities with considerable
      variation in the mix of the production methods, the CD exposures were remarkably
      similar in both calculated and measured values. The reductions in exposures were
      much more dependent upon the improvement of the production methods, rather than
      deliberate exposure control for occupational hygiene considerations. This is
      reasonable since the exposures were generally lower than the coeval exposure
      limits and/or guidelines. The estimated exposures were less than 100 ppm in the
      pre-1960 era and less than 10 ppm in the 1960-1980 era, less than 1 ppm 1980-1990
      era and less than 0.5 ppm thereafter. The exposures were categorized in four
      classes for VCM and six classes for CD. The characteristic class exposure values
      were used to cumulate individual exposures over time with a quantification of the
      potential range for exposures that are reasonably certain to ascribe correct
      ranking to job classes.

PMID- 16989795
TI  - An SPR immunosensor for human cardiac troponin T using specific binding avidin to
      biotin at carboxymethyldextran-modified gold chip.
AB  - BACKGROUND: The cardiac troponin T (TnT) is a cardiospecific, highly sensitive
      marker for myocardial damage and is immediately released to bloodstream during
      the acute myocardial infarction (AMI). Surface plasmon resonance (SPR)
      immunosensor was developed for the quick detection of human cTnT in real time.
      METHODS: An SPR sensor streptavidin terminated self-assembled monolayer, which
      was used to binding biotinylated anti troponin T monoclonal antibodies, was
      developed. RESULTS: The cTnT was determined from successive injections with a
      linear range from 0.03 up to 6.5 ng/ml. The detection limit was 0.01 ng/ml
      corresponding to a resonant angle change of 1.28 millidegrees. The system
      presented a good repeatability with 3.4% of variation between run after
      regeneration of the coated surface with a solution of 1% SDS. The effects of
      blocking of non-specific adsorption using different solutions were studied. It
      was possible to measure the cTnT without dilution of the human serum with good
      specificity and reproducibility. CONCLUSION: This sensor is practical and offer
      quick response in interval of 800 s.

PMID- 16989796
TI  - Plasma holotranscobalamin compared with plasma cobalamins for assessment of
      vitamin B12 absorption; optimisation of a non-radioactive vitamin B12 absorption
      test (CobaSorb).
AB  - BACKGROUND: A recently developed non-radioactive vitamin B(12) absorption test
      (CobaSorb) was further explored to identify the best marker for reflection of
      vitamin B(12) absorption and to determine the duration of the test. METHODS:
      Seventy-eight healthy individuals (age 21-81 years) were given three oral doses
      of 9 microg vitamin B(12) per day for 5 successive days. Non-fasting blood
      samples were collected on days 1 to 5 before administration of vitamin B(12) and
      on day 8. Cobalamins and holotranscobalamin were measured. RESULTS: Performance
      of the vitamin B(12) absorption test was evaluated in individuals with
      holotranscobalamin or cobalamins below the 75% percentiles. We used a change
      greater than 2xCV(day-to-day) in holotranscobalamin (22%) and cobalamins (12%) to
      indicate a change caused by absorption of vitamin B(12). Among individuals with a
      baseline holotranscobalamin below the 75% percentile (<75 pmol/L, n=57), 98% had
      an increase in holotranscobalamin >22% from day 1 to day 3. In contrast, only 72%
      of the individuals with baseline cobalamins below the 75% percentile (<335
      pmol/L, n=57) had an increase in cobalamins >12%. CONCLUSIONS: In healthy
      individuals with baseline holotranscobalamin <75 pmol/L, vitamin B(12) absorption
      is well reflected by an increase in holotranscobalamin after 2 days
      administration of oral vitamin B(12).

PMID- 16989797
TI  - Expression of PCNA, cytokeratin, Bcl-2 and p53 during chemoprevention of hamster
      buccal pouch carcinogenesis by ethanolic neem (Azadirachta indica) leaf extract.
AB  - OBJECTIVES: To evaluate the effect of ethanolic neem leaf extract (ENLE) on cell
      proliferation, differentiation and apoptosis associated proteins during 7,12
      dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP)
      carcinogenesis. DESIGN AND METHODS: Hamsters were divided into four groups. The
      right buccal pouches of animals in group 1 were painted with 0.5% DMBA three
      times a week. Animals in group 2 painted with DMBA as in group 1, received in
      addition, intragastric administration of ENLE (200 mg/kg bw) on days alternate to
      DMBA application. Group 3 animals were given ENLE (200 mg/kg bw) alone. Animals
      in group 4 served as control. All the animals were sacrificed after an
      experimental period of 14 weeks. The expression of proliferating cell nuclear
      antigen (PCNA), cytokeratin, Bcl-2 and p53 in the buccal pouch tissues were
      investigated using immunohistochemical staining. In addition, the expression of
      p53 was confirmed by Western blot analysis. RESULTS: Topical application of DMBA
      for 14 weeks induced buccal pouch carcinomas associated with increased expression
      of PCNA, mutant p53 and Bcl-2 and decreased expression of cytokeratin.
      Administration of ENLE significantly inhibited the development of HBP carcinomas
      as revealed by decreased expression of PCNA, mutant p53 and Bcl-2 and
      overexpression of cytokeratin. CONCLUSION: These findings suggest that ENLE
      exerts its anticancer properties by inhibiting cell proliferation and inducing
      differentiation and apoptosis.

PMID- 16989798
TI  - Processing focus structure and implicit prosody during reading: differential ERP
      effects.
AB  - Several recent studies have shown that focus structural representations influence
      syntactic processing during reading, while other studies have shown that implicit
      prosody plays an important role in the understanding of written language. Up
      until now, the relationship between these two processes has been mostly
      disregarded. The present study disentangles the roles of focus structure and
      accent placement in reading by reporting event-related brain potential (ERP) data
      on the processing of contrastive ellipses. The results reveal a positive-going
      waveform (350-1300 ms) that correlates with focus structural processing and a
      negativity (450-650 ms) interpreted as the correlate of implicit prosodic
      processing. The results suggest that the assignment of focus as well as accent
      placement are obligatory processes during reading.

PMID- 16989799
TI  - Comparative multiresolution wavelet analysis of ERP spectral bands using an
      ensemble of classifiers approach for early diagnosis of Alzheimer's disease.
AB  - Early diagnosis of Alzheimer's disease (AD) is becoming an increasingly important
      healthcare concern. Prior approaches analyzing event-related potentials (ERPs)
      had varying degrees of success, primarily due to smaller study cohorts, and the
      inherent difficulty of the problem. A new effort using multiresolution analysis
      of ERPs is described. Distinctions of this study include analyzing a larger
      cohort, comparing different wavelets and different frequency bands, using
      ensemble-based decisions and, most importantly, aiming the earliest possible
      diagnosis of the disease. Surprising yet promising outcomes indicate that ERPs in
      response to novel sounds of oddball paradigm may be more reliable as a biomarker
      than the more commonly used responses to target sounds.

PMID- 16989800
TI  - Epigenetic discrimination by mouse metaphase II oocytes mediates asymmetric
      chromatin remodeling independently of meiotic exit.
AB  - In mammalian fertilization, paternal chromatin is exhaustively remodeled, yet the
      maternal contribution to this process is unknown. To address this, we prevented
      the induction of meiotic exit by spermatozoa and examined sperm chromatin
      remodeling in metaphase II (mII) oocytes. Methylation of paternal H3-K4 and H3-K9
      remained low, unlike maternal H3, although paternal H3-K4 methylation increased
      in zygotes. Thus, mII cytoplasm can sustain epigenetic asymmetry in a cell-cycle
      dependent manner. Paternal genomic DNA underwent oocyte-mediated cytosine
      demethylation and acquired maternally-derived K12-acetylated H4 (AcH4-K12)
      independently of microtubule assembly and maternal chromatin. AcH4-K12 persisted
      without typical maturation-associated deacetylation, irrespective of paternal pan
      genomic cytosine methylation. Contrastingly, somatic cell nuclei underwent rapid
      H4 deacetylation; sperm and somatic chromatin exhibited asymmetric AcH4-K12
      dynamics simultaneously within the same mII oocyte. Inhibition of somatic histone
      deacetylation revealed endogenous histone acetyl transferase activity. Oocytes
      thus specify the histone acetylation status of given nuclei by differentially
      targeting histone deacetylase and acetyl transferase activities. Asymmetric H4
      acetylation during and immediately after fertilization was dispensable for
      development when both parental chromatin sets were hyperacetylated. These studies
      delineate non-zygotic chromatin remodeling and suggest a powerful model with
      which to study de novo genomic reprogramming.

PMID- 16989801
TI  - Pitx1 determines the morphology of muscle, tendon, and bones of the hindlimb.
AB  - The vertebrate forelimb and hindlimb are serially homologous structures; however,
      their distinctive morphologies suggest that different mechanisms are associated
      with each limb type to give rise to limb-type identity. Three genes have been
      implicated in this process; T-box transcription factors Tbx5 and Tbx4, which are
      expressed in the forelimb and hindlimb, respectively, and a paired-type
      homeodomain transcription factor Pitx1, expressed in the hindlimb. To explore the
      roles of Pitx1 and Tbx4 in patterning the hindlimb, we have ectopically
      misexpressed these genes in the mouse forelimb using transgenic methods. We have
      developed a novel technique for visualising the structure and organisation of
      tissues in limbs in 3D using optical projection tomography (OPT). This approach
      provides unparalleled access to understanding the relationships between
      connective tissues during development of the limb. Misexpression of Pitx1 in the
      forelimb results in the transformation and translocation of specific muscles,
      tendons, and bones of the forelimb so that they acquire a hindlimb-like
      morphology. Pitx1 also upregulates hindlimb-specific factors in the forelimb,
      including Hoxc10 and Tbx4. In contrast, misexpression of Tbx4 in the forelimb
      does not result in a transformation of limb-type morphology. These results
      demonstrate that Pitx1, but not Tbx4, determines the morphological identity of
      hindlimb tissues.

PMID- 16989802
TI  - Levels of mesenchymal FGFR2 signaling modulate smooth muscle progenitor cell
      commitment in the lung.
AB  - Fibroblast growth factor (FGF) signaling has been shown to regulate lung
      epithelial development but its influence on mesenchymal differentiation has been
      poorly investigated. To study the role of mesenchymal FGF signaling in the
      differentiation of the mesenchyme and its impact on epithelial morphogenesis, we
      took advantage of Fgfr2c(+/Delta) mice, which due to a splicing switch express
      Fgfr2b in mesenchymal tissues and manifest Apert syndrome-like phenotypes. Using
      a set of in vivo and in vitro studies, we show that an autocrine FGF10-FGFR2b
      signaling loop is established in the mutant lung mesenchyme, which has several
      consequences. It prevents the entry of the smooth muscle progenitors into the
      smooth muscle cell (SMC) lineage and results in reduced fibronectin and elastin
      deposition. Levels of Fgf10 expression are raised within the mutant mesenchyme
      itself. Epithelial branching as well as epithelial levels of FGF and canonical
      Wnt signaling is dramatically reduced. These defects result in arrested
      development of terminal airways and an "emphysema like" phenotype in postnatal
      lungs. Our work unravels part of the complex interactions that govern normal lung
      development and may be pertinent to understanding the basis of respiratory
      defects in Apert syndrome.

PMID- 16989803
TI  - microRNAs as oncogenes and tumor suppressors.
AB  - microRNAs (miRNAs) are a new class of non-protein-coding, endogenous, small RNAs.
      They are important regulatory molecules in animals and plants. miRNA regulates
      gene expression by translational repression, mRNA cleavage, and mRNA decay
      initiated by miRNA-guided rapid deadenylation. Recent studies show that some
      miRNAs regulate cell proliferation and apoptosis processes that are important in
      cancer formation. By using multiple molecular techniques, which include Northern
      blot analysis, real-time PCR, miRNA microarray, up- or down-expression of
      specific miRNAs, it was found that several miRNAs were directly involved in human
      cancers, including lung, breast, brain, liver, colon cancer, and leukemia. In
      addition, some miRNAs may function as oncogenes or tumor suppressors. More than
      50% of miRNA genes are located in cancer-associated genomic regions or in fragile
      sites, suggesting that miRNAs may play a more important role in the pathogenesis
      of a limited range of human cancers than previously thought. Overexpressed miRNAs
      in cancers, such as mir-17-92, may function as oncogenes and promote cancer
      development by negatively regulating tumor suppressor genes and/or genes that
      control cell differentiation or apoptosis. Underexpressed miRNAs in cancers, such
      as let-7, function as tumor suppressor genes and may inhibit cancers by
      regulating oncogenes and/or genes that control cell differentiation or apoptosis.
      miRNA expression profiles may become useful biomarkers for cancer diagnostics. In
      addition, miRNA therapy could be a powerful tool for cancer prevention and
      therapeutics.

PMID- 16989805
TI  - Regulation of Gremlin expression in the posterior limb bud.
AB  - Proper outgrowth of the limb bud requires a positive feedback loop between Sonic
      hedgehog (Shh) in the zone of polarizing activity (ZPA) and Fgfs in the overlying
      apical ectodermal ridge. The Bmp antagonist Gremlin is expressed in a domain
      anterior to the ZPA and is thought to act as a signaling intermediate between Shh
      and Fgf. It is currently unclear whether Shh acts directly or indirectly to
      initiate and maintain Gremlin. In this study, we confirm that Bmp activity is
      necessary and sufficient for induction of Gremlin. Beads soaked in the Bmp
      antagonist Noggin downregulate Gremlin, while beads soaked in Bmp2 cause its
      upregulation. Furthermore, Bmp2 is also capable of upregulating Gremlin in
      oligozeugodactyly mutant limbs that lack Shh activity, demonstrating that Gremlin
      expression does not depend on the combined exposure to both these factors. In
      spite of the ability of Bmp2 to induce Gremlin, beads soaked in high
      concentrations of Bmp2 downregulate Gremlin around the bead without apparent
      induction of cell death, whereas another target gene Msx2 is upregulated around
      the bead. Consistent with this concentration-dependent effect, we find that low
      concentrations of Bmp2 upregulate Gremlin while high concentrations of Bmp2
      downregulate Gremlin in limb mesenchyme cultures. These data implicate Bmp
      activity as a required intermediate in the Shh-Fgf4 signaling loop. Though we
      show that Bmp activity is sufficient to upregulate Gremlin, Gremlin expression is
      excluded from a posterior domain of the limb, and expansion of this domain as
      limb outgrowth proceeds is important in terminating the Shh-Fgf4 signaling loop.
      We find that the posterior limb is refractory to Gremlin induction in response to
      Bmp2, suggesting that termination of the Shh-Fgf4 signaling loop results from
      inability of Bmp activity to induce Gremlin in the posterior. In contrast, in the
      oligozeugodactyly limb, we find that beads soaked in Bmp2 can induce Gremlin in
      the posterior, demonstrating that Shh activity is required for exclusion of
      Gremlin in the posterior. Finally, by blocking Shh activity with cyclopamine, we
      find evidence that continued Shh activity is also required to maintain
      refractoriness to Gremlin expression in response to Bmp activity.

PMID- 16989804
TI  - Formin-2 is required for spindle migration and for the late steps of cytokinesis
      in mouse oocytes.
AB  - Female meiotic divisions in higher organisms are asymmetric and lead to the
      formation of a large oocyte and small polar bodies. These asymmetric divisions
      are due to eccentric spindle positioning which, in the mouse, requires actin
      filaments. Recently Formin-2, a straight actin filaments nucleator, has been
      proposed to control spindle positioning, chromosome segregation as well as first
      polar body extrusion in mouse oocytes. We reexamine here the possible role of
      Formin-2 during mouse meiotic maturation by live videomicroscopy. We show that
      Formin-2 controls first meiotic spindle migration to the cortex but not
      chromosome congression or segregation. We also show that the lack of first polar
      body extrusion in fmn2(-/-) oocytes is not due to a lack of cortical
      differentiation or central spindle formation but to a defect in the late steps of
      cytokinesis. Indeed, Survivin, a component of the passenger protein complex, is
      correctly localized on the central spindle at anaphase in fmn2(-/-) oocytes. We
      show here that attempts of cytokinesis in these oocytes abort due to phospho
      myosin II mislocalization.

PMID- 16989806
TI  - YM440, a novel hypoglycemic agent, protects against nephropathy in Zucker fatty
      rats via plasma triglyceride reduction.
AB  - The novel hypoglycemic agent, YM440 ((Z)-1,4-bis{4-[(3,5-dioxo-1,2,4
      oxadiazolidin-2-yl) methyl] phenoxy}but-2-ene) is a ligand of the peroxisome
      proliferator-activated receptor, (PPAR) gamma. YM440 has been shown to counteract
      insulin resistance in diabetic rodent models. However, it is not clear whether
      this compound has a significant effect on hyperlipidemia in vivo. Hyperlipidemia
      has been reported to be a risk factor for the early development of renal disease.
      The aim of this study is to examine the effects of chronic treatment with YM440
      on hyperlipidemia and renal injury in obese Zucker fatty (ZF) rats. Treatment of
      8-week-old ZF rats with YM440 (100 mg/kg/day) for 16 weeks decreased plasma
      triglyceride and cholesterol concentrations. YM440 markedly reduced the rate of
      progression of both albuminuria and proteinuria. YM440 normalized urinary N
      acetyl-beta-D-glucosaminidase (NAG) activity, which is a marker for renal
      proximal tubular damage, and ameliorated the rise in systolic blood pressure
      compared to the vehicle control. YM440 also blocked the development of
      nephromegaly. Histological analyses revealed that both glomerular area expansion
      and tubular cast accumulation gradually lessened in YM440-treated ZF rats.
      Regression analyses between the plasma triglyceride levels and the renal
      parameters (urinary protein excretion and albumin excretion) indicated that the
      renal parameters correlated positively with the plasma triglyceride levels. In
      conclusion, the hypolipidemic effects of YM440 prevent renal injury in ZF rats.
      YM440 might be useful for preventing the early development of diabetic
      nephropathy in subjects with type 2 diabetes by ameliorating metabolic control
      problems.

PMID- 16989807
TI  - Neuroprotective effects of the stable nitroxide compound Tempol on 1-methyl-4
      phenylpyridinium ion-induced neurotoxicity in the Nerve Growth Factor
      differentiated model of pheochromocytoma PC12 cells.
AB  - Nerve growth factor (NGF) differentiated pheochromocytoma PC12 cells exposed to 1
      methyl-4-phenylpyridinium (MPP+) toxin were used as an in vitro pharmacological
      model of Parkinson's disease to examine the neuroprotective effects of 4-hydroxy
      2,2,6,6-tetramethyl piperidine-n-oxyl (Tempol), a free radical scavenger and a
      superoxide dismutase-mimetic compound. MPP+-induced PC12 cell death was measured
      72 h after exposure to 1.5 mM MPP+ by the release of lactate dehydrogenease,
      caspase-3 activation and stimulation of survival and stress mitogen-activated
      protein kinases. Exposure of PC12 cells to MPP+ activated ERK1 and ERK2 (forty
      fold over control after 72 h), JNK1 and JNK2 (fourfold after 48 h) and p-38alpha
      (tenfold after 24 h). Pretreatment of PC12 cells with 500 microM Tempol, 1 h
      before induction of the MPP+ insult, reduced by 70% the release of LDH into the
      medium, inhibited caspase-3 activity by 30% and improved by 33% mitochondrial
      function, effects correlated with a 70% reduction in ERK1 and ERK2
      phosphorylation activity. These findings support the neuroprotective effect of
      Tempol in the MPP+-induced PC12 cell death model and its use as a potential drug
      for treatment of Parkinson's disease.

PMID- 16989808
TI  - Oral administration of nicorandil enhances the survival of ischemic skin flaps in
      rats.
AB  - Nicorandil has an anti-apoptotic effect on ischemic myocardium through the
      activation of ATP-sensitive potassium (K(ATP)) channel. We tested the hypothesis
      that oral administration of nicorandil had a protective effect on ischemic skin
      flaps. A cranially based skin flap measuring 3x7 cm in full thickness was made on
      the back of rats. The rats were divided into a control group and 8 nicorandil
      groups (group 1-8) according to different doses and timings of administration. On
      day 7 at 5 cm, groups 1 to 6 (10 or 30 mg/kg twice per day for 3 days starting at
      24 h before, 0.5 h before or 0.5 h after the operation) showed significantly
      higher blood perfusion change rate (73.3+/-2.9%-79.1+/-4.1% vs. 25.9+/-8.6%,
      P<0.01), and significantly higher survival rate (68.8+/-4.8-75.2+/-8.2% vs.
      47.0+/-2.8%, P<0.05) than the control group. Many more surviving blood vessels
      were also observed in these groups. In contrast, no significant effects were
      found either in group 7 (30 mg/kg twice per day for 3 days starting 24 h after
      the operation) or group 8 (30 mg/kg once at 0.5 h after the operation). We did
      not find an angiogenic effect of nicorandil in vitro. Therefore, our results
      confirmed that the oral administration of nicorandil could protect tissues from
      necrosis in ischemic skin flaps. In addition, its protective effect depends on
      the time of first administration and the duration.

PMID- 16989809
TI  - Cannabinoid-improgan cross-tolerance: Improgan is a cannabinomimetic analgesic
      lacking affinity at the cannabinoid CB1 receptor.
AB  - Improgan is a non-opioid analgesic which does not act at known histamine or
      cannabinoid receptors. Because improgan antinociception is blocked by low doses
      of a cannabinoid CB1 antagonist, the present experiments determined if
      development of cannabinoid tolerance in mice would alter improgan
      antinociception. Twice-daily injections of Delta9-tetrahydrocannabinol (THC, 10
      mg/kg, s.c.) for 3.5 days induced 47-54% and 42-56% reductions in cannabinoid
      (WIN 55,212-2, 20 microg, i.c.v.) and improgan (30 microg, i.c.v.)
      antinociception, respectively, as compared with responses from vehicle-treated
      groups. Because improgan lacks cannabinoid-like side effects in rats, and does
      not act directly on cannabinoid CB1 receptors, the finding that development of
      cannabinoid tolerance reduces improgan antinociception suggests that this drug
      may release endocannabinoids, or activate novel cannabinoid sites. Either
      possibility offers the potential for developing new types of analgesics.

PMID- 16989810
TI  - Cryptotanshinone inhibits cyclooxygenase-2 enzyme activity but not its
      expression.
AB  - Cyclooxygenase-2 (COX-2) is a key enzyme that catalyzes the biosynthesis of
      prostaglandins from arachidonic acid and plays a critical role in some
      pathologies including inflammation, neurodegenerative diseases and cancer.
      Cryptotanshinone is a major constituent of tanshinones, which are extracted from
      the medicinal herb Salvia miltiorrhiza Bunge, and has well-documented
      antioxidative and anti-inflammatory effects. This study confirmed the remarkable
      anti-inflammatory effect of cryptotanshinone in the carrageenan-induced rat paw
      edema model. Since the action of cryptotanshinone on COX-2 has not been
      previously described, in the present study, we further examined the effect of
      cryptotanshinone on cyclooxygenase activity in the exogenous arachidonic acid
      stimulated insect sf-9 cells, which highly express human COX-2 or human COX-1,
      and on cyclooxygenases expression in human U937 promonocytes stimulated by
      lipopolysaccharide (LPS) plus phorbolmyristate acetate (PMA). Cryptotanshinone
      reduced prostaglandin E2 synthesis and reactive oxygen species generation
      catalyzed by COX-2, without influencing COX-1 activity in cloned sf-9 cells. In
      PMA plus LPS-stimulated U937 cells, cryptotanshinone had negligible effects on
      the expression of COX-1 and COX-2, at either a mRNA or protein level. These
      results demonstrate that the anti-inflammatory effect of cryptotanshinone is
      directed against enzymatic activity of COX-2, not against the transcription or
      translation of the enzyme.

PMID- 16989812
TI  - Inhibitory effects of d-mannose on trypanosomatid lysis induced by Serratia
      marcescens.
AB  - Studies were carried out on the effects of different carbohydrates on the lysis
      of Trypanosoma cruzi, Trypanosoma rangeli and erythocytes caused by the bacteria
      Serratia marcescens variants SM 365 and RPH. High concentrations of d-mannose
      were found to protect T. cruzi and T. rangeli markedly diminishing the lysis
      caused by S. marcescens. However, this carbohydrate is unable to interfere with
      the hemolysis induced by SM 365 and RPH variants. These results showed that the
      trypanolytic effect induced by S. marcescens SM 365 and RPH variants is dependent
      on d-mannose and distinct from the hemolytic activity, strongly suggesting that
      bacterial fimbriae are relevant to S. marcescens in lysis of parasites.

PMID- 16989811
TI  - Global expression of NGF promotes sympathetic axonal growth in CNS white matter
      but does not alter its parallel orientation.
AB  - Axonal regeneration is normally limited after injuries to CNS white matter.
      Infusion of neurotrophins has been successful in promoting regenerative growth
      through injured white matter but this growth generally fails to extend beyond the
      infusion site. These observations are consistent with a chemotropic effect of
      these factors on axonal growth and support the prevailing view that neurotrophin
      induced axonal regeneration requires the use of gradients, i.e., gradually
      increasing neurotrophin levels along the target fiber tract. To examine the
      potential of global overexpression of neurotrophins to promote, and/or modify the
      orientation of, regenerative axonal growth within white matter, we grafted nerve
      growth factor (NGF) responsive neurons into the corpus callosum of transgenic
      mice overexpressing NGF throughout the CNS under control of the promoter for
      glial fibrillary acidic protein. One week later, glial fibrillary acidic protein
      and chondroitin sulfate proteoglycan immunoreactivity increased within injured
      white matter around the grafts. NGF levels were significantly higher in the
      brains of transgenic compared with non-transgenic mice and further elevated
      within injury sites compared with the homotypic region of the non-injured side.
      Although there was minimal outgrowth from neurons grafted into non-transgenic
      mice, extensive parallel axonal regeneration had occurred within the corpus
      callosum up to 1.5 mm beyond the astrogliotic scar (the site of maximum NGF
      expression) in transgenic mice. These results demonstrate that global
      overexpression of neurotrophins does not override the constraints limiting
      regenerative growth to parallel orientations and suggest that such factors need
      not be presented as positive gradients to promote axonal regeneration within
      white matter.

PMID- 16989813
TI  - Trichinella spiralis: strong antibody response to a 49 kDa newborn larva antigen
      in infected rats.
AB  - In this work, we analyzed the kinetics of anti-Trichinella spiralis newborn larva
      (NBL) antibodies (Ab) and the antigenic recognition pattern of NBL proteins and
      its dose effects. Wistar rats were infected with 0, 700, 2000, 4000 and 8000
      muscle larvae (ML) and bled at different time intervals up to day 31 post
      infection (p.i.). Ab production was higher with 2000 ML dose and decreased with
      8000, 4000 and 700 ML. Abs were not detected until day 10, peaked on day 14 for
      the 2000 ML dose and on day 19 for the other doses and thereafter declined slowly
      from 19 to 31 days p.i. In contrast, Abs to ML increased from day 10, peaked on
      day 19 and remained high until the end of the study. Abs bound strongly at least
      to three NBL components of 188, 205 and 49 kDa. NBL antigen of 188 and 205 kDa
      were recognized 10-26 days p.i. and that of 49 kDa from day 10 to day 31 p.i. A
      weak recognition towards antigens of 52, 54, 62 and 83 kDa was also observed
      during the infection. An early recognition of 31, 43, 45, 55, 68 and 85 kDa ML
      antigens was observed whereas the response to those of 43, 45, 48, 60, 64 and 97
      kDa (described previously as TSL-1 antigens) occurred late in the infection. A
      follow-up of antigen recognition up to day 61 with the optimal immunization dose
      (2000 ML) evidenced a decline of Ab production to the 49 kDa NBL antigen 42 days
      p.i., which suggested antigenic differences with the previously reported 43 kDa
      ML antigen strongly recognized late in the infection. To analyze the stage
      specificity of the 49 kDa NBL antigen, polyclonal antibodies (PoAb) were obtained
      in rats immunized with 49 kDa NBL antigen. PoAb reacted strongly with the 49 kDa
      NBL component in NBL total soluble extract but no reactivity was observed with
      soluble antigen of the other T. spiralis stages. Albeit with less intensity, the
      49 kDa component was also recognized by PoAb together with other antigens of 53,
      97 and 107 kDa, in NBL excretory-secretory products (NBL-ESP). Thus, our results
      reveal differences in the kinetics of anti-NBL and ML Ab responses. While anti
      NBL Abs declined slowly from day 19 until the end of the experiment, Abs to ML
      antigen remained high in the same period. It is remarkable the optimal Ab
      response to NBL antigens with 2000 ML infective dose and the reduced number of
      NBL antigens identified throughout the experimental T. spiralis infection,
      standing out the immunodominant 49 kDa antigen. Interestingly, this antigen,
      which was prominently expressed in NBL somatic proteins, was also detected in NBL
      ESP.

PMID- 16989814
TI  - WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic
      reticulum.
AB  - The WFS1 gene, encoding an endoplasmic reticulum (ER) membrane glycoprotein, is
      mutated in Wolfram syndrome characterized by diabetes mellitus and optic atrophy.
      Herein, Ca(2+) dynamics were examined in WFS1-knockdown and -overexpressing
      HEK293 cells. Studies using ER-targeted Ca(2+)-sensitive photoprotein aequorin
      demonstrated WFS1 protein to positively modulate ER Ca(2+) levels by increasing
      the rate of Ca(2+) uptake. Furthermore, Ca(2+) imaging with Fura-2 showed the
      magnitude of the store-operated Ca(2+) entry to parallel WFS1 expression levels.
      These data indicate that WFS1 protein participates in the regulation of cellular
      Ca(2+) homeostasis, at least partly, by modulating the filling state of the ER
      Ca(2+) store.

PMID- 16989815
TI  - Quantitative comparison of the efficiency of antibodies against S1 and S2 subunit
      of SARS coronavirus spike protein in virus neutralization and blocking of
      receptor binding: implications for the functional roles of S2 subunit.
AB  - Neutralizing effects of antibodies targeting the C-terminal stalk (S2) subunit of
      the spike protein of severe acute respiratory syndrome coronavirus have
      previously been reported, although its mechanism remained elusive. In this study,
      high titered mouse antisera against the N-terminal globular (S1) and S2 subunits
      of the S protein were generated and total immunoglobulin G (IgG) was purified
      from these antisera. The efficiency of these purified IgGs in virus
      neutralization and blocking of receptor binding were compared quantitatively
      using virus neutralization assay and a previously developed cell-based receptor
      binding assay, respectively. We demonstrated that anti-S1 IgG neutralizes the
      virus and binds to the membrane associated S protein more efficiently than anti
      S2 IgG does. Moreover, both anti-S1 and anti-S2 IgGs were able to abolish the
      binding between S protein and its cellular receptor(s), although anti-S1 IgG
      showed a significantly higher blocking efficiency. The unexpected blocking
      ability of anti-S2 IgG towards the receptor binding implied a possible role of
      the S2 subunit in virus docking process and argues against the current hypothesis
      of viral entry. On the other hand, the functional roles of the previously
      reported neutralizing epitopes within S2 subunit were investigated using an
      antigen specific antibody depletion assay. Depletion of antibodies against these
      regions significantly diminished, though not completely abolished, the
      neutralizing effects of anti-S2 IgG. It suggests the absence of a major
      neutralizing domain on S2 protein. The possible ways of anti-S2 IgGs to abolish
      the receptor binding and the factors restricting anti-S2 IgGs to neutralize the
      virus are discussed.

PMID- 16989816
TI  - Modulation of LRP6-mediated Wnt signaling by molecular chaperone Mesd.
AB  - LRP6 is a Wnt coreceptor at the cell surface. Here, we report that a specialized
      molecular chaperone Mesd modulates LRP6-mediated Wnt signaling and how different
      LRP6 mutants exhibit differential effects on Wnt signaling. We found that
      overexpression of increasing amounts of the full-length LRP6 enhances Wnt
      signaling in a dose dependent manner only in the presence of a co-expression of
      the molecular chaperone Mesd, which promotes LRP6 folding and maturation to the
      cell surface. We also demonstrated that LRP6 mutant lacking the intracellular
      domain impedes LRP6 cell surface expression and Wnt signaling in a dominant
      negative fashion by sequestering Mesd from promoting LRP6 folding. Our results
      present novel mechanisms by which Mesd and LRP6 modulate Wnt signaling.

PMID- 16989817
TI  - Rational selection of small molecules that increase transcription through the GAA
      repeats found in Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive trinucleotide repeat disease
      with no effective therapy. Expanded GAA repeats in the first intron of the FRDA
      gene are thought to form unusual non-B DNA conformations that decrease
      transcription and subsequently reduce levels of the encoded protein, frataxin.
      Frataxin plays a crucial role in iron metabolism and detoxification. To discover
      small molecules that increase transcription through the GAA repeat region in
      FRDA, we have made stable cell lines containing a portion of expanded intron 1
      fused to a GFP reporter. Small molecules identified using the competition
      dialysis method were found to increase FRDA-intron 1-reporter gene expression.
      One of these compounds, pentamidine, increases frataxin levels in patient cells.
      Thus our approach can be used to detect small molecules of potential therapeutic
      value in FRDA.

PMID- 16989818
TI  - The effects of charge-neutralizing mutation D6.30N on the functions of CB1 and
      CB2 cannabinoid receptors.
AB  - Charge-neutralizing mutation D6.30N of the human cannabinoid receptor subtype 1
      (CB1) and cannabinoid receptor subtype 2 (CB2) cannabinoid receptors was made to
      test two hypotheses: (1) D6.30 may be crucial for the functions of CB1 and CB2
      receptors. (2) D6.30 may participate in an ionic lock with R3.50 that keeps the
      receptors in an inactive conformation. Specific ligand binding and ligand-induced
      inhibition of forskolin-stimulated cAMP accumulation were observed with human
      embryonic kidney epithelial cell line (HEK293) cells expressing wild-type CB1 and
      CB2, as well as CB1D6.30N and CB2D6.30N mutant receptors. There was however a
      decrease in maximum response of the mutant receptors compared to their wild-type
      counterparts, suggesting that D6.30 is essential for full activation of both CB1
      and CB2 receptors. Both CB1D6.30N and CB2D6.30N demonstrated a level of
      constitutive activity no greater than that of their wild-type counterparts,
      indicating that either D6.30 does not participate in a salt bridge with R3.50, or
      the salt bridge is not critical for keeping cannabinoid receptors in the inactive
      conformation.

PMID- 16989819
TI  - JNK mediates TGF-beta1-induced epithelial mesenchymal transdifferentiation of
      mouse transformed keratinocytes.
AB  - In this study we analyzed the role of the c-Jun N-terminal kinases (JNK) pathway
      in the TGF-beta1 stimulation of urokinase-type plasminogen activator (uPA),
      initial stages of epithelial-mesenchymal transdifferentiation (EMT) and cell
      migration. TGF-beta1 induces JNK phosphorylation, c-Jun transactivation and AP1
      activation. The involvement of JNK was evaluated using dominant negative mutants
      SEK-1 AL, JNK and cJun, depletion of JNK1,2 proteins by treatment of cells with
      antisense oligonucleotides, as well as the chemical inhibitor SP600125. Our
      results demonstrated that the JNK pathway is required in the TGF-beta1
      enhancement of uPA, fibronectin, E-cadherin delocalization, actin re-organization
      and vimentin expression, concomitant with the induction of cell migration. These
      results allow us to suggest a role of JNK in the TGF-beta1 induction of EMT in
      relation with the stimulation of malignant properties of mouse transformed
      keratinocytes.

PMID- 16989820
TI  - Expression of tryptophan hydroxylase in developing mouse taste papillae.
AB  - Gustatory papillae and associated taste buds receive and process chemical
      information from the environment. In mammals, their development takes place
      during the late phase of embryogenesis. However, the cellular factors that
      regulate the differentiation of taste papillae remain largely unknown. Here, we
      show by quantitative real time RT-PCR that both isoforms of tryptophan
      hydroxylase (TPH1 and TPH2), the first and rate limiting enzyme of serotonin (5
      HT) synthesis, are expressed in developing circumvallate papillae. Immuno
      staining experiments further indicated that TPH is localized both in gustatory
      fibers and in differentiated taste receptor cells. These results point to the
      synthesis of 5-HT in gustatory papillae, and allow one to hypothesize that the
      development of taste buds might be modulated by serotonin.

PMID- 16989821
TI  - The incorporation of nucleoside analogs by human immunodeficiency virus type 1
      reverse transcriptase decreases in the presence of polyamines.
AB  - Nucleoside analogs (NAs) are an important class of anti-retroviral compounds used
      against human immunodeficiency virus (HIV). We have analyzed the potential effect
      of polyamines on the incorporation of NAs during DNA synthesis by HIV type-1 (HIV
      1) reverse transcriptase (RT). The polyamines exert the ability to decrease the
      incorporation of various dideoxynucleoside triphosphates (ddATP, ddTTP or ddCTP)
      with both RNA/DNA and DNA/DNA substrates in the following order:
      spermine>spermidine>putrescine. The reduction is a sequence-independent effect,
      taking place at different sequence context. The results suggest that polyamines
      might affect the inhibition of reverse transcription by nucleoside analogs HIV-1
      RT directed.

PMID- 16989822
TI  - Characterization of homogentisate prenyltransferases involved in plastoquinone-9
      and tocochromanol biosynthesis.
AB  - A cDNA of Chlamydomonas reinhardtii encoding a plastidial homogentisate
      prenyltransferase was identified. Functional expression studies in Escherichia
      coli revealed that the enzyme possessed properties similar to the
      prenyltransferase of Arabidopsis thaliana encoded by At3g11950 but different from
      the phytyltransferases of A. thaliana and Synechocystis. Unlike the
      phytyltransferases, the C. reinhardtii and the respective A. thaliana enzyme
      showed highest activities with solanesyl diphosphate, but were hardly active with
      phytyl diphosphate. Hence, these data provide evidence that the latter represent
      homogentisate solanesyltransferases involved in plastoquinone-9 biosynthesis.
      Overexpression of At3g11950 in A. thaliana, however, suggests that the
      solanesyltransferase can affect tocopherol biosynthesis as well.

PMID- 16989823
TI  - Compact archaeal variant of heme A synthase.
AB  - The N- and C-terminal halves of the heme A synthase polypeptide of Bacillus
      subtilis, and many other organisms, are homologous. This indicates that these
      enzyme proteins originate from a tandem duplication and fusion event of a gene
      encoding a protein half as large. The ape1694 gene of the hyperthermophilic
      archaeon Aeropyrum pernix encodes a protein that is similar to the hypothetical
      small primordial protein. We demonstrate that this A. pernix protein is a heat
      stable membrane bound heme A synthase designated cCtaA. The case of cCtaA is
      unusual in evolution in that the primordial-like protein has not become extinct
      and apparently carries out the same function as the twice as large more
      diversified heme A synthase protein variant found in most cytochrome a-containing
      organisms.

PMID- 16989824
TI  - Paneth cell antimicrobial peptides: topographical distribution and quantification
      in human gastrointestinal tissues.
AB  - Antimicrobial peptides and proteins are key effectors of innate immunity,
      expressed both by circulating phagocytic cells and by epithelial cells of mucosal
      tissues. In the human small intestine, Paneth cells are secretory epithelial
      cells that express the antimicrobials human alpha-defensin-5 (HD5), HD6, lysozyme
      and secretory phospholipase A(2) (sPLA(2)), and recent studies have implicated
      reduced HD5 and HD6 expression levels in the pathogenesis of ileal Crohn's
      disease. However, expression levels of these molecules have not been determined
      routinely by techniques that readily permit quantitative comparisons of their
      distribution between tissues and samples. Using quantitative real-time PCR with
      external standards and Northern blot analysis, we compared expression levels of
      mRNA encoding these four Paneth cell antimicrobial peptides, as well as
      circulating human neutrophil defensins in several different gastrointestinal
      tissues and the bone marrow. HD5 and HD6 were the most abundant antimicrobials
      expressed in the small intestine. The concentration of HD5 mRNA is approximately
      5 x 10(5) copies per 10ng RNA in the jejunum and ileum; HD6 mRNA levels were
      about six times lower than those of HD5. With the exception of low levels in the
      pancreas (10(3) copies/10 ng RNA), the expression of HD5 and HD6 in tissues other
      than small intestine was at or below detectable limits. The expression of sPLA2
      and lysozyme mRNA was observed in the small intestine (approximately, 3 x 10(3)
      and 9 x 10(3) copies/10 ng RNA, respectively), but also in several other tissues.
      Lysozyme expression was high in the duodenum (10(5) copies/10 ng RNA), and the
      protein localized to both Brunner's glands in the lamina propria and Paneth
      cells. By comparison, the hematopoietic alpha-defensins HNP1-3 mRNA were detected
      at 6 x 10(5) copies per 10 ng RNA in the bone marrow. These quantitative RT-PCR
      data from healthy tissues represents the first quantitative topographical
      assessment of antimicrobial expression in the gastrointestinal tract and provides
      a means to directly compare expression levels between healthy tissues and disease
      specimens for multiple antimicrobial peptides.

PMID- 16989825
TI  - Decreased suppression of interleukin-6 after treatment with medroxyprogesterone
      acetate and danazol in endometrial stromal cells of women with adenomyosis.
AB  - OBJECTIVE: To examine changes in local cytokine production in the eutopic
      endometrium of adenomyosis after treatment with medroxyprogesterone acetate (MPA)
      and danazol. DESIGN: Prospective cohort study. SETTING: Tertiary university
      hospital. PATIENT(S): Twenty-four women with adenomyosis (study group) and 22
      women without adenomyosis (control group). INTERVENTION(S): Eutopic endometrium
      was separated into single endometrial stromal cells (ESCs), and was cultured in
      vitro alone, with MPA (10(-7) M), or with danazol (10(-7) M) for 8 days. MAIN
      OUTCOME MEASURE(S): Messenger RNA expression of interleukin (IL)-6, IL-8, and
      tumor necrosis factor-alpha in ESCs, and their concentrations in the supernatants
      of ESCs. RESULT(S): A significant decrease of IL-6 concentration in the
      supernatant, measured by ELISA, was found with time of ESCs cultured with MPA and
      danazol in the control group, but not in adenomyosis. The IL-6 mRNA in ESCs
      determined by real-time quantitative polymerase chain, as well as its
      concentration in the supernatant, was much higher in adenomyosis than that in the
      control group after treatment with MPA and danazol for 8 days. CONCLUSION(S):
      Medroxyprogesterone acetate and danazol appeared to have a decreased effect on
      the suppression of IL-6 liberated by ESCs in adenomyosis. This aberrant secretion
      of IL-6 might play a role in the formation of ectopic endometrial implants in
      adenomyosis.

PMID- 16989826
TI  - Vaginally administered estroprogestinic decreases serum inhibin A and inhibin B
      levels and reduces endometrial thickness.
AB  - OBJECTIVE: Serum levels of inhibin A, inhibin B, FSH, and LH were measured in
      healthy volunteers before and during oral or vaginal estroprogestinic
      administration. In addition, the effect on endometrial thickness and on
      follicular growth pattern were also assessed by vaginal ultrasound. DESIGN:
      Prospective study. SETTING: University of Siena. PATIENT(S): Seventeen healthy
      fertile women. INTERVENTION(S): This open-label study was performed in 10 healthy
      volunteers, who were assigned to vaginal ethinylestradiol (15 microg) and
      etonogestrel (120 microg), one ring to be used for one cycle, after
      stratification for the ovulation day in a pretreatment cycle. A similar study on
      seven women assigned to oral ethinylestradiol (20 microg) and levonorgestrel (100
      microg) was considered, to compare the effects of the two different routes of
      administration. Blood samples were collected the cycle before (days 8-10) and
      during (days 8-10) vaginal ring insertion and serum inhibin B, inhibin A, FSH,
      and LH levels were measured by ELISA. Concomitantly, transvaginal ultrasound was
      performed in all subjects for endometrial and follicular growth assessment. MAIN
      OUTCOME MEASURE(S): Inhibin A, inhibin B, FSH, and LH levels. RESULT(S): Vaginal
      administration induced a significant decrease of serum inhibin A, inhibin B, FSH,
      and LH. No significant changes in inhibin B and FSH secretion were observed
      during oral contraceptive (OC) administration, whereas LH and inhibin A levels
      significantly decreased. Endometrial thickness and ovarian volume decreased
      significantly during vaginal ring insertion, but not after OC administration.
      CONCLUSION(S): The present findings showed that treatment with vaginal
      estroprogestinic decreases serum inhibin A and inhibin B levels, the follicular
      diameter, and endometrial thickness, showing a rapid and significant effect with
      the vaginal route.

PMID- 16989827
TI  - Identification of novel polymorphisms in the nuclear protein genes and their
      relationship with human sperm protamine deficiency and severe male infertility.
AB  - OBJECTIVE: To screen populations of fertile men, severely infertile men, and
      infertility patients with aberrations in the protamine-1-to-protamine-2 ratio
      (P1/P2) for clinically relevant alterations in the P1, P2, transition protein 1
      (TP1), and transition protein 2 (TP2) genes. DESIGN: Prospective case-control
      study. SETTING: University-based infertility clinic. PATIENT(S): Ninety-six
      fertile men, 96 severely infertile men, and 96 infertility patients with
      aberrations in the sperm P1/P2 ratio. INTERVENTION(S): Sperm nuclear protein
      extraction, gel electrophoresis, and densitometry to evaluate the P1/P2 ratios of
      infertility patients. DNA extraction, polymerase chain reaction (PCR), and gene
      sequencing to screen the nuclear protein genes. MAIN OUTCOME MEASURE(S): Sperm
      P1/P2 ratios and single nucleotide polymorphisms (SNPs) in the sperm nuclear
      protein genes (P1, P2, TP1, and TP2). RESULT(S): Fifteen SNPs were identified in
      the nuclear protein genes, 12 of which were previously unreported. Five variants
      were identified that resulted in amino acid changes (one in P1, one in TP1, and
      three in TP2). The frequency of the 15 SNPs was similar in protamine-deficient
      patients, severely infertile patients, and fertile controls. CONCLUSION(S): A
      number of SNPs are present in the testis-specific nuclear protein genes. However,
      the gene variants do not appear to underlie protamine deficiency and severe male
      infertility.

PMID- 16989828
TI  - Morbid adhesion of the placenta after hysteroscopic lysis of intrauterine
      adhesions.
AB  - OBJECTIVE: To report a case of morbidly adherent placenta in a patient who had
      previously undergone hysteroscopic lysis of intrauterine adhesions. DESIGN: Case
      report. SETTING: Large district general hospital within the National Health
      Service in the U.K. PATIENT(S): A healthy 32-year-old woman who had conceived
      following hysteroscopic lysis of intrauterine adhesions. INTERVENTION(S):
      Watchful expectancy following the diagnosis of morbidly adherent placenta
      immediately after delivery. MAIN OUTCOME MEASURE(S): Retention of the uterus and
      therefore reproductive function. RESULT(S): Successful resolution of the retained
      placenta following watchful expectancy. CONCLUSION(S): Watchful expectancy is a
      valid option in the management of a morbidly adherent placenta.

PMID- 16989829
TI  - Immunohistochemical expression of endometrial L-selectin ligand is higher in
      donor egg recipients with embryonic implantation.
AB  - OBJECTIVE: To correlate L-selectin ligand (LSL) expression in human endometrium
      with embryonic implantation. DESIGN: Retrospective cohort analysis. SETTING:
      University-based fertility center. PATIENT(S): Donor egg recipients (DERs) who
      underwent programmed hormonal replacement for ET with prior mock cycle luteal
      phase endometrial biopsy. INTERVENTION(S): Immunohistochemical expression of LSL
      using MECA-79 antibody was examined. Slides were scored with a new scoring
      system, the IHC-Level (range 0-4) as follows: strength of staining-absent (0),
      weak (1), or strong (2); plus distribution of staining-absent (0), <50% of tissue
      (1), and >50% (2). Cellular apex and cytoplasm were scored independently in both
      the endometrial glandular and surface epithelium. MAIN OUTCOME MEASURE(S):
      Endometrial LSL expression in pregnant versus nonpregnant patients. RESULT(S):
      MECA-79 IHC-Level of the apex of surface epithelium was significantly higher for
      pregnant versus nonpregnant DERs (3.8 vs. 3.4). When controlling for embryo
      morphology, there continues to be a significant difference in apex score on
      surface epithelium (3.8 vs. 3.3, respectively). The new scoring system results
      correlated with an established scoring system, the HSCORE. CONCLUSION(S): We
      demonstrate significantly higher expression of LSL at the apex of human
      endometrial surface epithelium obtained from DERs with embryonic implantation.
      Furthermore, we present the IHC-Level, a method of evaluating
      immunohistochemistry that may be applied to other markers of endometrial
      receptivity.

PMID- 16989830
TI  - Brown oocytes: implications for assisted reproductive technology.
AB  - Fertilization, embryo development, and successful pregnancy can be achieved after
      transfer of embryos derived from brown oocytes at the same rate as embryos from
      morphologically normal oocytes. Therefore, brown oocytes are probably normal and
      this morphological criterion does not seem to be indicative of any adverse
      outcome in IVF.

PMID- 16989831
TI  - Corticosterone and the transition from courtship behavior to dispersal in male
      red-sided garter snakes (Thamnophis sirtalis parietalis).
AB  - Seasonal modulation of baseline glucocorticoid concentrations as well as the
      sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis plays an important
      role in supporting critical life-history events such as seasonal reproduction and
      migration. Despite numerous studies on adrenocortical modulation, little is known
      about the exact timing of this seasonal modulation with respect to critical life
      history stages. We tested the hypothesis that seasonal modulation of the HPA axis
      during the spring mating season in male red-sided garter snakes (Thamnophis
      sirtalis parietalis) is temporally linked to the mechanisms regulating dispersal.
      We compared hormonal responses to capture stress in courting male red-sided
      garter snakes collected from the den site and den perimeter to those of
      dispersing snakes collected 0.6 km from the den. We also investigated possible
      changes in steroid hormones during the spring mating season. These studies
      support previous findings that plasma androgen and corticosterone concentrations
      significantly decline over the mating season. Our results demonstrate that males
      0.6 km into a 15-20 km route to the feeding grounds have lower baseline
      corticosterone concentrations than male snakes actively courting at the den.
      Dispersing males also exhibit a typical stress response marked by a significant
      increase in corticosterone while actively courting males do not. Capture stress
      did not significantly influence androgen concentrations of either courting or
      dispersing male red-sided garter snakes. There were no significant differences in
      body composition indices among male snakes collected from the den, den perimeter,
      or 0.6 km away from the den. However, we did observe a significant negative
      correlation between baseline corticosterone levels and body composition indices.
      These data suggest that breeding is a distinct stage accompanied by specific
      physiological parameters that differ from those during dispersal to the feeding
      grounds. Our results indicate that declining baseline corticosterone
      concentrations may play a role in the behavioral switch between actively courting
      and dispersing (i.e., feeding) in the late spring.

PMID- 16989832
TI  - The sounds of music in the operating room.
AB  - BACKGROUND: Little information is available about the effect of music on the
      operating room (OR) staff. PURPOSE: The objective of this study was to evaluate
      the perception of the influence of music on physicians and nurses working in the
      OR. METHODS: A questionnaire was designed and 250 copies were distributed to the
      doctors and nurses working in the OR at three hospitals. One hundred and seventy
      one returned the completed questionnaire and were included in this study.
      RESULTS: 63% of the participants listen to music on a regular basis in the OR.
      Classical music is the most requested (58%) and most of the responders do not
      choose the type of music according to the type of the procedure. In our study,
      the nurses were more likely to listen to music and the willingness is higher
      among the female responders. The desired volume is lower as age increases and
      78.9% of the participants claimed that music in the OR makes them calmer and more
      efficient. CONCLUSION: According to our study, music has a positive effect on the
      staff working in the operating rooms.

PMID- 16989834
TI  - A comparison of paediatric soccer, gaelic football and rugby injuries presenting
      to an emergency department in Ireland.
AB  - OBJECTIVES: Children presenting with sport related injuries (SRIs) as a result of
      soccer, rugby and gaelic football are frequently seen in an emergency medicine
      (EM) setting in Ireland. A comparison of the demographics of injuries in these
      three sports has however not previously been performed. The purpose of this study
      was to provide up-to-date data on the nature of these SRIs. METHOD: Data was
      collected retrospectively on all children (<17 years of age), injured in these
      three sports, presenting to an emergency medicine department over 6 months, and
      was entered into a database for analysis. RESULTS: Retrospective analysis was
      performed on 23,000 charts, and 409 SRIs were identified over a 6-month period.
      None of the children reported using any form of protective gear, and 27% reported
      a previous presentation to the emergency department with a SRI. Most injuries
      were as a result of soccer (56%), with 24% occurring in gaelic football, and 20%
      occurring in rugby. The predominant mechanism of injury was different in each
      sport, in soccer-falls (38%), in gaelic football-collisions with objects (balls)
      (37%), and in rugby-collision with persons (55%). Although the predominant type
      of injury in soccer and gaelic football was a fracture, accounting for 50% and
      42% of injuries, respectively, in rugby however, skin/soft tissue injuries
      presented more commonly, accounting for 44% of injuries. When the general site of
      injury was investigated, the upper limb accounted for the majority of SRIs in
      each sport. In the management of SRIs, oral analgesics were prescribed in 50%,
      however, it was observed that no use was made of topical, intramuscular or rectal
      analgesic routes of administration. In addition it was observed that RICE/general
      injury advice was given in only 27%, physiotherapy was requested in 2%, and no
      injury prevention advice was given to any child. Overall, 8% required admission.
      CONCLUSIONS: The data provided from this study may raise awareness of the nature
      of SRIs affecting children in each of these three sports, and may be useful in
      formulating much needed injury prevention strategies.

PMID- 16989835
TI  - Posttraumatic stress in long-term young adult survivors of childhood cancer: a
      questionnaire survey.
AB  - BACKGROUND: Posttraumatic stress is one of many psychological late effects in
      young adult survivors of childhood cancer and needs to be explored thoroughly.
      OBJECTIVE: The purpose of this study was to examine the characteristics and
      correlates of posttraumatic stress symptoms in a sample of young adult survivors
      of childhood cancer. DESIGN: Cross-sectional and correlational descriptive design
      was used. Data was collected by a mailed survey. The University of California at
      Los Angeles Post Traumatic Stress Disorder Index (PTSDI) was the measure selected
      for the evaluation of posttraumatic stress. SETTING: The study took place in a
      medical center in the Eastern part of the United States. PARTICIPANTS: The
      inclusion criteria for participants were: (a) diagnosis of childhood cancer
      between birth and 19 years of age; (b) 3 or more years post successful completion
      of cancer treatment; (c) free of active cancer; (d) at least 19 years of age; and
      (e) able to read and write English. A total of 51.1% (N=46) of the potentially
      eligible survivors responded to the survey. The analysis was based on the data
      from 45 respondents who had a mean age of 27.4 years. RESULTS: The mean PTSDI
      score was 15.7 (SD=11.0, range=0-43). Thirteen percent (n=6) of participants had
      PTSDI scores that exceeded the cutoff point of 32, which is considered indicative
      of clinically significant posttraumatic stress disorder (PTSD). Participants who
      lived alone (t=-2.17, p=.035), had no health insurance (t=2.08, p=.044) and did
      not have a history of bone marrow transplantation (t=4.52, p=.000) reported
      significantly higher scores on PTSDI than others. The clinically significant PTSD
      group had a significantly higher rate of living alone than the non-PTSD group
      (p=.038). CONCLUSION: Cancer-related posttraumatic stress emerges in childhood
      cancer survivors in young adulthood. Health care providers should screen
      childhood cancer survivors for posttraumatic stress so that referrals can be made
      to provide survivors with further assistance.

PMID- 16989836
TI  - Transmission of Toxoplasma gondii in an urban population of domestic cats (Felis
      catus).
AB  - Toxoplasma gondii is a protozoan parasite that infects humans and animal species
      worldwide. The relative importance of each potential transmission route in the
      complex life cycle of this coccidia is largely unknown, due to the lack of
      studies taking into account all routes simultaneously. In this study, we analyzed
      the transmission of T. gondii in an urban population of stray cats captured
      between 1993 and 2004. Analyzing prevalence, our aim was to determine which
      factors influence transmission in this population. Specific anti-T. gondii IgG
      antibodies were detected using the modified agglutination test. Firstly, we
      analyzed the kinetics of antibody titers in cats captured several times, using
      mixed linear models and correspondence analysis. We showed that antibody titers
      did not vary significantly with time and that titer 40 was the best threshold to
      separate individuals into two serological groups. Overall, prevalence was only
      18.6%, thus transmission of T. gondii is infrequent in this population. As
      expected, a highly significant association was detected between age and presence
      of IgG antibodies. Prevalence was lowest in kittens aged 3-4 months, suggesting
      that newborn kittens may carry maternal antibodies and that vertical transmission
      is rare. After taking into account the effect of age, logistic regression showed
      that antibody carriage was related to factors that possibly related to the
      survival of oocysts: localization in the study site, origin of the cats, maximal
      temperatures and rain. Our results suggest that in this population, vertical
      transmission is rare, low predation limits prevalence, and oocyst survival is a
      determining factor in the risk of infection. We discuss the more general
      importance of conditions determining oocyst survival in the life cycle of T.
      gondii.

PMID- 16989837
TI  - alpha-Defensin: link between inflammation and atherosclerosis.
AB  - BACKGROUND: Several markers of inflammation predict the risk of thrombotic
      cardiovascular events in patients with atherosclerosis. However, the mechanism by
      which vascular inflammation promotes atherothrombotic disease is incompletely
      understood. Human neutrophil peptides 1-3, also known as alpha-defensins, are
      found in human atherosclerotic arteries, inhibit LDL metabolism and fibrinolysis
      and promote Lp(a) binding. We asked, therefore, if alpha-defensins are risk
      factors for the presence and severity of atherosclerosis. METHODS: alpha-Defensin
      was measured in skin biopsies taken from 53 male patients (age 58.7+/-11.3 years,
      mean+/-S.D.) immediately prior to coronary artery catheterization. Other
      established risk factors were measured concurrently. The correlation between
      alpha-defensin deposition in the skin and the severity of the coronary artery
      disease (CAD) was examined. RESULTS: A statistically significant correlation was
      observed between the amount of alpha-defensin in skin and the severity of CAD
      (R=0.40, p=0.003). Multiple regression analysis showed that skin alpha-defensin
      is an independent predictor for CAD severity (F=4.68, p=0.035). Logistic
      regression analysis confirmed that skin alpha-defensin independently predicted
      the likelihood for CAD (p=0.016, odds estimate 5.97, 95% CL 1.4-24.2).
      CONCLUSIONS: The deposition of alpha-defensin in the skin is a strong independent
      predictor of CAD in men. These results suggest a link between neutrophil
      activation and progression of atherosclerosis and provide a novel approach to
      assessment of risk factors for CAD.

PMID- 16989838
TI  - The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern
      African population.
AB  - OBJECTIVE: Missense mutations in the proprotein convertase subtilisin/kexin type
      9 gene (PCSK9) can cause familial hypercholesterolemia. However, two nonsense
      variants of PCSK9, Y142X and C679X, found in approximately 2% of black American
      subjects, are associated with a 28% reduction in mean low density lipoprotein
      (LDL)-cholesterol. We sought to determine the frequency and effect of these
      nonsense variants in an African population. METHODS AND RESULTS: PCSK9 genotypes
      were determined in 653 black African women attending two antenatal clinics in
      Zimbabwe. C679X occurred in 3.7% of subjects and was associated with a 27%
      reduction in LDL-cholesterol (1.6+/-0.3 mmol/L versus 2.2+/-0.7 mmol/L in non
      carriers). We did not observe the Y142X variant. CONCLUSIONS: Our results show
      that the PCSK9 C679X variant has a marked cholesterol-lowering effect.

PMID- 16989839
TI  - Erectile dysfunction predicts generalised cardiovascular disease: evidence from a
      case-control study.
AB  - AIMS: To determine whether idiopathic erectile dysfunction, in the absence of
      overt cardiovascular disease or cardiovascular risk factors, is associated with
      vascular or autonomic dysfunction. METHODS: We studied 49 men with ED (without
      known cardiovascular risk factors or disease) and 50 age-matched controls, aged
      40-70 years. Macrovascular endothelial function was examined by brachial artery
      ultrasonography and microvascular function by venous occlusion plethysmography.
      Blood pressure measurement and electrocardiography were performed lying and
      standing, and the 30:15 RR ratio calculated. RESULTS: Body mass index,
      testosterone, fasting lipids and glucose did not differ significantly between
      groups. Standing pulse pressure was higher (50+/-1mm Hg versus 43+/-2mm Hg,
      p<0.004) and 30:15 RR ratio lower (0.97+/-0.01 versus 1.01+/-0.01, p<0.02) in the
      ED group. Flow-mediated dilatation of the brachial artery was not significantly
      different between groups. Flow debt repayment during forearm reactive hyperaemia
      was lower in the ED group (7.2+/-0.7 ml versus 9.5+/-0.8 ml per 100ml, p<0.02)
      than in controls. CONCLUSIONS: Men with idiopathic ED have evidence of
      endothelial dysfunction in forearm resistance vessels, increased pulse pressure
      and impaired heart rate variability. This supports the concept that erectile
      dysfunction is a predictor of cardiovascular dysfunction and a precursor of
      clinical cardiovascular disease.

PMID- 16989840
TI  - Enhanced apoB48 metabolism in lipoprotein lipase X447 homozygotes.
AB  - RATIONALE: Lipoprotein lipase (LPL) X447 homozygotes are characterized by
      enhanced conversion of TRL apoB100. Here, we set out to investigate whether this
      LPL variant is also associated with enhanced apoB48 clearance. Therefore, we
      evaluated apoB48 kinetics in X447 homozygotes in the fed state by infusion of
      isotope L-[1-(13)C]-valine and subsequent compartmental modeling. METHODS AND
      RESULTS: ApoB48 metabolism was assessed in five X447 homozygotes (X/X genotype)
      and five S447 homozygotes (S/S genotype). Subjects were continuously fed and
      received infusion of stable isotope L-[1-(13)C]-valine. Results were analyzed by
      SAAM II modeling. Fasting (2.4-fold, p=0.02) as well as non-fasting (1.6-fold,
      p=0.09) apoB48 concentration was increased in the X447 homozygotes compared to
      S447 homozygotes. In addition, the X447 homozygotes exhibited a 1.7-fold higher
      apoB48 poolsize (p=0.04). Interestingly, apoB48 fractional catabolic rate (FCR)
      was 1.9-fold higher (p=0.007) and apoB48 synthesis was more than two-fold higher
      (p=0.006) in the X447 homozygotes compared to S447 homozygotes. CONCLUSION: In
      the present study, we show that X447 homozygotes exhibit enhanced apoB48
      clearance. Previously, these homozygotes were shown to present with enhanced
      apoB100 TRL conversion. Combined, this LPLS447X gain of function variant affects
      apoB48 as well as apoB100 TRL metabolism.

PMID- 16989841
TI  - Steady-state force-velocity relation in human multi-joint movement determined
      with force clamp analysis.
AB  - To study the force-velocity characteristics of human knee-hip extension movement,
      a dynamometer, in which force was controlled by a servo system, was developed.
      Seated subjects pressed either bilaterally or unilaterally a force plate, a
      horizontal position of which was servo-controlled so as to equalize the measured
      force and a force command generated by a computer at a time resolution of 2 ms
      (force clamp). The force command was based on the relation between maximum
      isometric force and foot position within the range between 70% and 90% of "leg
      length" (LL: longitudinal distance between the sole of the foot and the hip
      joint), so that the same force relative to the maximum isometric force was
      consistently applied regardless of the foot position. By regulating the force
      according to this function, the force-velocity relation was determined. The force
      velocity relation obtained was described by a linear function (n=17, r=-0.986 for
      80% LL, r=-0.968 for 85% LL) within a range of force between 0.1 and 0.8F(0)
      (maximum isometric force). The maximum force extrapolated from the linear
      regression (F(max)) coincided with F(0) (n=17, F(0)/F(max)=1.00+/-0.09 for 80% LL
      and 1.00+/-0.20 for 85% LL). Also, the velocity at zero force (V(max)) was
      obtained from the extrapolation. When compared to the bilateral movements,
      unilateral movements gave rise to a smaller F(max) but the same V(max),
      suggesting that V(max) is independent of force and therefore represents the
      proper unloaded velocity. It is suggested that some neural mechanisms may be
      involved in the force-velocity relation of the knee-hip extension movement, and
      make it exhibit a linear appearance rather than a hyperbola.

PMID- 16989842
TI  - Analysis of OSPAR priority pharmaceuticals using high-performance liquid
      chromatography-electrospray ionisation tandem mass spectrometry.
AB  - The occurrence and potential adverse effects of pharmaceutical compounds in the
      aquatic environment have received much scientific interest. Presented are
      analytical methodologies for the determination of 10 of the pharmaceuticals
      listed on the Oslo and Paris Commission for the protection of the Marine
      Environment of the North East Atlantic (OSPAR) hazardous substances website. In
      addition to these 10 substances, the chemical fluoxetine (Prozac) was also
      investigated. The performance characteristics of a combined solid phase
      extraction (SPE) isolation and high-performance liquid chromatography
      electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS) procedure have
      been determined. Extraction efficiencies were obtained for a variety of SPE
      sorbents, following this initial investigation. Strata-X (Phenomenex, UK) was
      selected for further development. The extraction method performed satisfactorily
      for the majority of the 11 compounds analysed, with recoveries of over 60% for
      most of the compounds and relative standard deviations of between 4 and 13%. The
      recoveries of chloroquine and closantel were below 50% but the method provides
      semi-quantitative information regarding the occurrence of these compounds.
      Separation of the analytes was made using a C18 Luna analytical column
      (Phenomenex, UK) and mass spectra were obtained using an ion trap mass
      spectrometer operated in both positive and negative electrospray ionisation
      modes. Limits of detection for all compounds ranged from 1 to 20 ng/l, making the
      method suitable for low level environmental analysis. Of the selected surface
      water and treated sewage effluent samples (n = 6) analysed, chlorpromazine,
      fluoxetine and miconazole were detected in concentrations ranging from 7 to 34
      ng/l. The chemicals determined using this procedure fall into a variety of
      pharmaceutical classes including antipsychotics and tranquilisers resulting in an
      analytical method that contains compounds from diverse chemical classes.

PMID- 16989843
TI  - Electrokinetic pumping effects of charged porous media in microchannels using the
      lattice Poisson-Boltzmann method.
AB  - The electrokinetic pumping characteristics of nanoscale charged porous media
      packed in microchannels are investigated using a mesoscopic evolution method.
      When the pore size of porous media is comparable to the thickness of electric
      double layer, the effects of particle surface potentials on the bulk electric
      potential distribution will not be negligible. The lattice Poisson-Boltzmann
      method provides an accurate numerical solution for such problems, which combines
      two sets of lattice evolution methods solving the nonlinear Poisson-Boltzmann
      equation for electric potential distribution and the Navier-Stokes equations for
      fluid flow, respectively. The effects of the finite particle size, the bulk ionic
      concentration, the external electric field strength and the surface potentials on
      the electroosmotic micropump performances are therefore studied. The results show
      that for a certain porosity the maximum pumping pressure is inversely
      proportional to the particle diameter and the flow rate under zero pressure drop
      increases with the particle size. The pumping flow rate decreases with the
      backpressure yet increases with the external electric field strength, linearly
      respectively. The averaged flow rate increases with the bulk ionic concentration
      and the particle surface potential, but is slightly influenced by the surface
      potentials of channel walls. The numerical results agree with the published
      experimental data while some results deviate from the predictions based on the
      macroscopic linear assumptions.

PMID- 16989844
TI  - Adsorption of a hazardous dye, erythrosine, over hen feathers.
AB  - Erythrosine is a popular dye that is widely used in cosmetics, foodstuffs,
      medicines, and textiles. It is highly toxic to mankind and can lead to many
      diseases including carcinogenicity. Removal of erythrosine has been carried out
      using waste material--hen feathers--as adsorbent. The effects of pH,
      concentration of the dye, temperature, and adsorbent dosage have been studied.
      Adsorption of erythrosine over hen feathers has been correlated with Freundlich
      and Langmuir isotherms and satisfies both models. The adsorption process has been
      found endothermic in nature and thermodynamic parameters, Gibb's free energy
      (DeltaG(0)), change in enthalpy (DeltaH(0)), and change in entropy (DeltaS(0))
      have been calculated. The paper also includes results on the kinetic measurements
      of adsorption of the dye on hen feathers at different temperatures. The
      adsorption follows a first-order kinetics at all the temperatures and values of
      the rate constant (k(ad)) have been calculated as 0.0179, 0.0177, and 0.0172 s(
      1) at 30, 40, and 50 degrees C, respectively. By rate expression and treatment of
      data it has been ascertained that the adsorption of erythrosine over hen feathers
      follows a particle diffusion mechanism.

PMID- 16989845
TI  - Surface properties of submicrometer silica spheres modified with
      aminopropyltriethoxysilane and phenyltriethoxysilane.
AB  - The surface of submicrometer silica spheres are modified with aminopropyl and
      phenyl groups through a one-step process. Various experimental techniques, i.e.,
      scanning electron microscopy (SEM), quasi-elastic light scattering (QELS),
      differential scanning calorimetry (DSC), thermogravimetry (TG), zeta potential
      measurement, nitrogen sorption, and water vapor and organic dye adsorption are
      used to comprehensively characterize the pure (TEOS particles) and modified
      silica particles. The SEM micrographs of the particles demonstrate that the
      modified particles are spherical with uniform size and shape. The particles
      modified with aminopropyl groups (APTES particles) show the highest isoelectric
      point (IEP) and the highest weight loss at 780 degrees C because of the basic
      nature of aminopropyl groups and the higher reactivity of
      aminopropyltriethoxysilane. The particles modified with the phenyl groups (PhTES
      particles) show the lowest water vapor adsorption because their surface is more
      hydrophobic than that of TEOS and APTES particles. The organic dye (brilliant
      blue FCF or BBF) adsorption experiments demonstrate that the adsorption capacity
      of the particles increases greatly after acidification. This is caused by the
      protonation of silanol groups and amine groups on the particle surface, which
      presents an enhanced electrostatic attraction with BBF anions. The APTES
      particles exhibit the highest dye adsorption due to the hydrophobic attractions
      and the enhanced electrostatic attractions from aminopropyl groups.

PMID- 16989846
TI  - Effect of floc structure on the rate of Brownian coagulation.
AB  - A modified expression for the Smoluchowski solution for the temporal evolution of
      the number concentration of flocs subject to Brownian coagulation is proposed,
      taking into account the effect of the growth of floc structure. In the proposed
      equation, the effect is expressed as a decrease of free volume in the liquid
      phase due to the increase of effective floc volume in accordance with the
      progress of coagulation. The validity of the proposed equation was tested by
      coagulation experiments using polystyrene latex particles. Direct counting of the
      number of flocs under microscopy provided accurate data on the temporal evolution
      of the number concentration of flocs. The obtained rate gradually increases in
      accordance with the growth of floc structure. This behavior agreed exactly with
      the prediction based on the proposed equation.

PMID- 16989847
TI  - Condensed film formation of binary mixtures of cetyltrimethylammonium bromide and
      cetyldimethylbenzylammonium chloride in a wide potential region at the
      mercury/electrolyte interface.
AB  - The adsorption of binary mixtures of cetyltrimethylammonium bromide (CTAB) and
      cetyldimethylbenzylammonium chloride (CDBACl) at the mercury/electrolyte
      interface was studied in various electrolyte systems. The optimum surfactant
      concentration and electrolyte ratio was searched for, to obtain the formation of
      a condensed film at as wide a potential range as possible at the highest
      temperature possible. The optimum conditions found were 2 x 10(-4) M CTAB and 2 x
      10(-4) M CDBACl in 0.07 M KF and 0.03 M KBr at 2 degrees C. The capacitances vs
      time curves were used for the reconstruction of isochronous capacitance vs
      potential curves. These curves showed that in that system the condensed film was
      formed in the potential range from -0.4 to -1.9 V vs Ag/AgCl in less than 220 s.
      The stability of this film, following the removal of the mercury drop from the
      solution, was also studied.

PMID- 16989848
TI  - Enhancement of titanium dioxide photocatalysis by water-soluble fullerenes.
AB  - Fullerenes are known for their unique electronic properties including high
      electron affinity. Although use of fullerenes for scavenging photo-generated
      electrons from titanium dioxide particles has been demonstrated, no attempts have
      been made to utilize the unique properties of fullerenes to increase the efficacy
      of photocatalysis. The present study has demonstrated that a mixture of water
      soluble polyhydroxy fullerenes (PHF) and titanium dioxide (anatase polymorph)
      enhances photocatalytic degradation of organic dye. The PHF molecules adsorbed to
      the surface of titanium dioxide due to electrostatic forces, with adsorption
      density being higher at lower pH values. The surface coverage of titanium dioxide
      nanoparticles by PHF molecules determined the extent of enhancement, with an
      optimum dosed weight ratio of PHF to titanium dioxide at 0.001. Hydroxylation and
      concomitant solubilization of fullerenes allow their unique electronic properties
      to be harnessed for photocatalysis.

PMID- 16989849
TI  - Investigations into the kinetics and thermodynamics of Sb(III) adsorption on
      goethite (alpha-FeOOH).
AB  - This study reports thermodynamic and kinetic data of Sb(III) adsorption from
      single metal solutions onto synthetic aqueous goethite (alpha-FeOOH). Batch
      equilibrium sorption experiments were carried out at 25 degrees C over a Sb:Fe
      molar range of 0.005-0.05 and using a goethite concentration of 0.44 g Fe/L.
      Experimental data were successfully modelled using Langmuir (R2 > or = 0.891) and
      Freundlich (R2 > or = 0.990) isotherms and the following parameters were derived
      from triplicate experiments: Kf = 1.903 +/- 0.030 mg/g and 1/n = 0.728 +/- 0.019
      for the Freundlich model and b = 0.021 +/- 0.003 L/mg and Qmax = 61 +/- 8 mg/g
      for the Langmuir model. The thermodynamic parameters determined were the
      equilibrium constant, Keq =1.323 +/- 0.045, and the Gibb's free energy, DeltaG0 =
      -0.692 +/- 0.083 kJ/mol. The sorption process is very fast. At a Sb:Fe molar
      ratio of 0.05, 40-50% of the added Sb is adsorbed within 15 min and a steady
      state is achieved. The experimental data also suggest that desorption can occur
      within 24 h of reaction due to the oxidation of Sb(III) on the goethite surface.
      Finally, calculated pH of the aqueous solution using MINTEQ2 agrees well with the
      measured pH (3.9 +/- 0.7; n = 30). At pH 4, the dominant Sb species in solution
      are Sb(OH)3 and HSbO2 which both likely adsorb as inner sphere complexes to the
      positively charged goethite surface.

PMID- 16989850
TI  - Aggregation of methyl orange probed by electrical impedance spectroscopy.
AB  - We present results of an electrical impedance spectroscopy investigation of the
      evolution of the aggregation of methyl orange (MO) in pure aqueous solutions as
      the concentration of the dye is varied. By applying the constant phase element
      (CPE) approximation to model the electrical response of the MO solutions, we have
      verified that the formation of dimers and oligomers can be recognized by specific
      signatures in the loss and capacitive components of the dielectric response of
      the system. We interpret these well-defined changes in the dielectric properties
      of the solutions as a result of molecular rearrangements caused by the
      aggregation process that alter the current circulation pathways and the electric
      dipole distribution. The fact that these specific changes in the dielectric
      behavior coincide with critical concentrations where dimer and oligomer formation
      in pure aqueous MO solutions are known to occur suggests that electrical
      impedance spectroscopy can be a competitive technique for the investigation of
      aggregation behavior in dyes and surfactants.

PMID- 16989851
TI  - Estimation of polymer-surface interfacial interaction strength by a contact AFM
      technique.
AB  - Atomic force microscopy (AFM) measurements were employed to assess polymer
      surface interfacial interaction strength. The main feature of the measurement is
      the use of contact-mode AFM as a tool to scratch off the polymer monolayer
      adsorbed on the solid surface. Tapping-mode AFM was used to determine the depth
      of the scraped recess. Independent determination of the layer thickness obtained
      from optical phase interference microscopy (OPIM) confirmed the depth of the AFM
      scratch. The force required for the complete removal of the polymer layer with no
      apparent damage to the substrate surface was determined. Polypropylene (PP), low
      density polyethylene (PE), and PP-grafted-maleic anhydride (PP-g-ma) were scraped
      off silane-treated glass slabs, and the strength of surface interaction of the
      polymer layer was determined. In all cases it was determined that the magnitude
      of surface interaction force is of the order of van der Waals (VDW) interactions.
      The interaction strength is influenced either by polymer ability to wet the
      surface (hydrophobic or hydrophilic interactions) or by hydrogen bonding between
      the polymer and the surface treatment.

PMID- 16989852
TI  - Controlled synthesis of highly dispersed TiO2 nanoparticles using SBA-15 as hard
      template.
AB  - Highly dispersed TiO2 nanoparticles were successfully synthesized by a wet
      impregnation method using SBA-15 as hard template for confining the growth of
      TiO2 nanocrystals, and then calcined at 550 degrees C in muffle furnace for 2 h.
      The as-synthesized samples were characterized with Fourier transform infrared
      spectra (FTIR), Raman spectroscopy, diffuse reflectance UV-visible spectroscopy
      (UV-vis), powder X-ray diffraction (XRD), small-angle X-ray diffraction (SAXRD),
      nitrogen adsorption, transmission electron microscopy (TEM) and photoluminescence
      spectra (PL). It was found that SBA-15 contained abundant silanol groups after
      removal of triblock copolymers by ethanol extraction and could easily adsorb a
      great number of titanium alkoxide via chemisorption. After subsequent hydrolysis
      of the anchored Ti complexes and calcination of the amorphous TiO2, anatase TiO2
      nanocrystals with spherical shape and uniform particle diameter of about 6 nm
      were formed. A blue shift was observed in UV-vis absorption spectra due to the
      quantum size effect of TiO2 nanoparticles. Moreover, the as-prepared TiO2
      nanoparticles showed a high PL intensity due to an increase in the recombination
      rate of photogenerated electrons and holes under UV light irradiation.

PMID- 16989853
TI  - Study of the selection mechanism of heavy metal (Pb2+, Cu2+, Ni2+, and Cd2+)
      adsorption on clinoptilolite.
AB  - The study was carried out on the sorption of heavy metals (Ni2+, Cu2+, Pb2+, and
      Cd2+) under static conditions from single- and multicomponent aqueous solutions
      by raw and pretreated clinoptilolite. The sorption has an ion-exchange nature and
      consists of three stages, i.e., the adsorption on the surface of microcrystals,
      the inversion stage, and the moderate adsorption in the interior of the
      microcrystal. The finer clinoptilolite fractions sorb higher amounts of the
      metals due to relative enriching by the zeolite proper and higher cleavage. The
      slight difference between adsorption capacity of the clinoptilolite toward lead,
      copper, and cadmium from single- and multicomponent solutions may testify to
      individual sorption centers of the zeolite for each metal. The decrease of nickel
      adsorption from multicomponent solutions is probably caused by the propinquity of
      its sorption forms to the other metals and by competition. The maximum sorption
      capacity toward Cd2+ is determined as 4.22 mg/g at an initial concentration of 80
      mg/L and toward Pb2+, Cu2+, and Ni2+ as 27.7, 25.76, and 13.03 mg/g at 800 mg/L.
      The sorption results fit well to the Langmuir and the Freundlich models. The
      second one is better for adsorption modeling at high metal concentrations.

PMID- 16989854
TI  - A novel fluorescent sensitive assay for detection of differential T cell mediated
      lysis of multiple adherent target cells.
AB  - There are few studies that have investigated T cell mediated lysis of adherent
      cells. We have developed a novel, rapid and sensitive fluorescent dye-swap assay
      that allows efficient detection of adherent target cell lysis. The assay allows
      simultaneous use of multiple differentially sensitised targets and facilitates
      concomitant surface or intracellular effector cell phenotypic analysis.

PMID- 16989855
TI  - A novel method for detecting neutralizing antibodies against therapeutic proteins
      by measuring gene expression.
AB  - The presence of neutralizing antibodies against protein therapeutics is a concern
      in the biomedical field. Such antibodies not only reduce the efficacy of protein
      therapeutics, but also impose potential dangers to the patients receiving them.
      To date, a small number of in vitro cell-based bioassays for detecting
      neutralizing antibodies against therapeutic proteins have been developed. Most of
      the existing assays, however, either involve the use of radioactive materials or
      have limited sensitivities and/or poor specificities. With advances in mRNA
      profiling and detection techniques, we have established a novel and non
      radioactive bioassay system using branched DNA (bDNA) technology for detecting
      protein-therapeutic neutralizing antibodies in patient serum. Our assay measures
      the variations of target gene expression that reflect the biologic effect of the
      therapeutic agent and the capability of the antibodies, if present, to neutralize
      the therapeutics. Compared with most existing assays, the new assay is more
      sensitive and specific, and completely eliminates the use of radioactive
      materials. Application of the new assay system can be widely expanded if new
      target genes and responding cell lines for other therapeutics are identified or
      engineered.

PMID- 16989856
TI  - New cell lines from Lymantria xylina (Lepidoptera: Lymantriidae):
      characterization and susceptibility to baculoviruses.
AB  - Four new cell lines, designated as NTU-LY-1 to -4, respectively, were established
      from the pupal tissues of Lymantria xylina Swinhoe (Lepidoptera: Lymantriidae).
      These cell lines have been cultured approximately 80 passages during 2 years in
      TNM-FH medium supplemented with 8% fetal bovine serum, at a constant temperature
      of 28 degrees C. Each line consists of three major morphological types: round
      cells, spindle-shaped cells, and giant cells. The characterization of these cell
      lines showed that they are different from previously established lines derived
      from related Lepidopteran species. All new lines were susceptible to the L.
      xylina multiple nucleopolyhedrovirus (LyxyMNPV) and appeared to have a good
      potential for studying this virus.

PMID- 16989857
TI  - Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human
      atrial cells are reduced in atrial fibrillation.
AB  - 5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients in
      sinus rhythm (SR) via activation of 5-HT(4) receptors, but its effects in atrial
      cells from patients with atrial fibrillation (AF) are unknown. The whole-cell
      perforated patch-clamp technique was used to record L-type Ca(2+) current
      (I(CaL)), action potential duration (APD) and arrhythmic activity at 37 degrees C
      in enzymatically isolated atrial cells obtained from patients undergoing cardiac
      surgery, in SR or with chronic AF. In the AF group, 5-HT (10microM) produced an
      increase in I(CaL) of 115+/-21% above control (n=10 cells, 6 patients) that was
      significantly smaller than that in the SR group (232+/-33%; p<0.05; n=27 cells,
      12 patients). Subsequent co-application of isoproterenol (1microM) caused a
      further increase in I(CaL) in the AF group (by 256+/-94%) that was greater than
      that in the SR group (22+/-6%; p<0.05). The APD at 50% repolarisation (APD(50))
      was prolonged by 14+/-3ms by 5-HT in the AF group (n=37 cells, 14 patients). This
      was less than that in the SR group (27+/-4ms; p<0.05; n=58 cells, 24 patients).
      Arrhythmic activity in response to 5-HT was observed in 22% of cells in the SR
      group, but none was observed in the AF group (p<0.05). Atrial fibrillation was
      associated with reduced effects of 5-HT, but not of isoproterenol, on I(CaL) in
      human atrial cells. This reduced effect on I(CaL) was associated with a reduced
      APD(50) and arrhythmic activity with 5-HT. Thus, the potentially arrhythmogenic
      influence of 5-HT may be suppressed in AF-remodelled human atrium.

PMID- 16989858
TI  - Using evolutionary information and ancestral sequences to understand the sequence
      function relationship in GLP-1 agonists.
AB  - Glucagon-like peptide-1 (GLP-1) is an incretin hormone with therapeutic potential
      for type 2 diabetes. A variety of GLP-1 sequences are known from amphibian
      species, and some of these have been tested here and found to be able to bind and
      activate the human GLP-1 receptor. While little difference was observed for the
      in vitro potency for the human GLP-1 receptor, larger differences were found in
      the enzymatic stability of these peptides. Two peptides showed increased
      enzymatic stability, and they group together phylogenetically, though they
      originate from Amphibia and Reptilia. We have used ancestral sequence
      reconstruction to analyze the evolution of these GLP-1 molecules, including the
      synthesis of new peptides. We find that the increased stability could not be
      observed in the resurrected peptides from the common ancestor of frogs, even
      though they maintain the ability to activate the human GLP-1 receptor. Another
      method, using residue mapping on evolutionary branches yielded peptides that had
      maintained potency towards the receptor and also showed increased stability. This
      represents a new approach using evolutionary data in protein engineering.

PMID- 16989859
TI  - A novel dimer interface and conformational changes revealed by an X-ray structure
      of B. subtilis SecA.
AB  - The SecA ATPase moves polypeptides post-translationally across the plasma
      membrane of eubacteria, but the mechanism of transport is still unclear. We
      describe the crystal structure of a novel dimeric form of Bacillus subtilis SecA.
      Dimerization of SecA occurs at the prominent groove formed by the nucleotide
      binding domain 2 (nbd2) and the preprotein cross-linking (ppx) domain. The dimer
      interface is very large, burying approximately 5400 A(2) of solvent accessible
      surface per monomer. Single cysteine disulfide cross-linking shows the presence
      of this novel SecA dimer in solution. In addition, other dimers also exist in
      solution, arguing that they all are in equilibrium with monomeric SecA and
      supporting the idea that the monomer may be the functional species. Dimerization
      of SecA causes an alpha-helix of one subunit to convert to a short beta-strand
      that participates in beta-sheet formation with strands in the other subunit. This
      conversion of secondary structure elements occurs close to the connection between
      the nbd1 and ppx domains, a potential site of interaction with translocation
      substrate. Comparing the different X-ray structures of B. subtilis SecA suggests
      that small changes in the nucleotide binding domains could be amplified via helix
      1 of the helical scaffold domain (hsd) to generate larger movements of the
      domains involved in polypeptide binding.

PMID- 16989860
TI  - One protein, two enzymes revisited: a structural entropy switch interconverts the
      two isoforms of acireductone dioxygenase.
AB  - Acireductone dioxygenase (ARD) catalyzes different reactions between O2 and 1,2
      dihydroxy-3-oxo-5-(methylthio)pent-1-ene (acireductone) depending upon the metal
      bound in the active site. Ni2+ -ARD cleaves acireductone to formate, CO and
      methylthiopropionate. If Fe2+ is bound (ARD'), the same substrates yield
      methylthioketobutyrate and formate. The two forms differ in structure, and are
      chromatographically separable. Paramagnetism of Fe2+ renders the active site of
      ARD' inaccessible to standard NMR methods. The structure of ARD' has been
      determined using Fe2+ binding parameters determined by X-ray absorption
      spectroscopy and NMR restraints from H98S ARD, a metal-free diamagnetic protein
      that is isostructural with ARD'. ARD' retains the beta-sandwich fold of ARD, but
      a structural entropy switch increases order at one end of a two-helix system that
      bisects the beta-sandwich and decreases order at the other upon interconversion
      of ARD and ARD', causing loss of the C-terminal helix in ARD' and rearrangements
      of residues involved in substrate orientation in the active site.

PMID- 16989861
TI  - Cryo electron microscopy reconstructions of the Leviviridae unveil the densest
      icosahedral RNA packing possible.
AB  - We solved the structures of the single-stranded RNA bacteriophages Qbeta, PP7 and
      AP205 by cryo-electron microscopy. On the outside, the symmetrized electron
      density maps resemble the previously described cryo-electron microscopy structure
      of MS2. RNA density is present inside the capsids, suggesting that the genomic
      RNA of Qbeta, PP7 and AP205, analogous to MS2, contains many coat protein-binding
      sites in addition to the hairpin on which assembly and packaging are initiated.
      All four bacteriophages harbour the same overall arrangement of the RNA, which is
      a unique combination of both triangles and pentagons. This combination has not
      been found in other icosahedral viruses, in which the RNA structures are either
      triangular or pentagonal. Strikingly, the unique RNA packing of the Leviviridae
      appears to deploy the most efficient method of RNA storage by obeying icosahedral
      symmetry.

PMID- 16989862
TI  - Identification of a collapsed intermediate with non-native long-range
      interactions on the folding pathway of a pair of Fyn SH3 domain mutants by NMR
      relaxation dispersion spectroscopy.
AB  - Recent 15N and 13C spin-relaxation dispersion studies of fast-folding mutants of
      the Fyn SH3 domain have established that folding proceeds through a low-populated
      on-pathway intermediate (I) where the central beta-sheet is at least partially
      formed, but without interactions between the NH2- and COOH-terminal beta-strands
      that exist in the folded state (F). Initial studies focused on mutants where
      Gly48 is replaced; in an effort to establish whether this intermediate is a
      general feature of Fyn SH3 folding a series of 15N relaxation experiments
      monitoring the folding of Fyn SH3 mutants N53P/V55L and A39V/N53P/V55L are
      reported here. For these mutants as well, folding proceeds through an on-pathway
      intermediate with similar features to those observed for G48M and G48V Fyn SH3
      domains. However, the 15N chemical shifts extracted for the intermediate indicate
      pronounced non-native contacts between the NH2 and COOH-terminal regions not
      observed previously. The kinetic parameters extracted for the folding of
      A39V/N53P/V55L Fyn SH3 from the three-state folding model F<-->I<-->U are in good
      agreement with folding and unfolding rates extrapolated to zero denaturant
      obtained from stopped-flow experiments analyzed in terms of a simplified two
      state folding reaction. The folding of the triple mutant was studied over a wide
      range of temperatures, establishing that there is no difference in heat
      capacities between F and I states. This confirms a compact folding intermediate
      structure, which is supported by the 15N chemical shifts of the I state extracted
      from the dispersion data. The temperature-dependent relaxation data simplifies
      data analysis because at low temperatures (< 25 degrees C) the unfolded state (U)
      is negligibly populated relative to I and F. A comparison between parameters
      extracted at low temperatures where the F<-->I exchange model is appropriate with
      those from the more complex, three-state model at higher temperatures has been
      used to validate the protocol for analysis of three-site exchange relaxation
      data.

PMID- 16989863
TI  - Connecticut nighttime safety belt use.
AB  - PROBLEM: Safety belt use in the United States, as measured over daylight hours,
      has risen steadily over recent years reaching 80% in 2004. Yet, using the
      National Highway Traffic Safety Administration's (NHTSA) Fatality Analysis
      Reporting System (FARS), safety belt use among fatally injured front seat
      outboard occupants of passenger vehicles was only between 42% and 46% for the
      years 1999 to 2003. One possible contributing factor is that safety belt use at
      night, when crash rates are highest, is lower than during the day. METHOD: A full
      statewide nighttime belt use observation survey was conducted in 2004. This
      survey was conducted simultaneously with Connecticut's annual full statewide
      daytime belt use survey. Night belt use observations of drivers and passengers
      are possible using newly available near military grade night vision goggles and
      handheld infrared spotlights. Both day and goggle-assisted night observations
      were conducted at 100 observation sites in Connecticut. Procedures for day and
      night observations were as nearly identical as possible. RESULTS: The night belt
      use rate was 6.4 percentage points lower than the day rate (83.0 vs. 76.6).
      Consistent with belt use among Connecticut fatalities, day versus night
      differences were greatest in urban areas. There was evidence that day versus
      night differences were greater before as compared to after a May 2004 belt use
      enforcement program.

PMID- 16989865
TI  - Bacterial gene regulation in diauxic and non-diauxic growth.
AB  - When bacteria are grown in a batch culture containing a mixture of two growth
      limiting substrates, they exhibit a rich spectrum of substrate consumption
      patterns including diauxic growth, simultaneous consumption, and bistable growth.
      In previous work, we showed that a minimal model accounting only for enzyme
      induction and dilution captures all the substrate consumption patterns [Narang,
      A., 1998a. The dynamical analogy between microbial growth on mixtures of
      substrates and population growth of competing species. Biotechnol. Bioeng. 59,
      116-121, Narang, A., 2006. Comparitive analysis of some models of gene regulation
      in mixed-substrate microbial growth, J. Theor. Biol. 242, 489-501]. In this work,
      we construct the bifurcation diagram of the minimal model, which shows the
      substrate consumption pattern at any given set of parameter values. The
      bifurcation diagram explains several general properties of mixed-substrate
      growth. (1) In almost all the cases of diauxic growth, the "preferred" substrate
      is the one that, by itself, supports a higher specific growth rate. In the
      literature, this property is often attributed to the optimality of regulatory
      mechanisms. Here, we show that the minimal model, which accounts for induction
      and growth only, displays the property under fairly general conditions. This
      suggests that the higher growth rate of the preferred substrate is an intrinsic
      property of the induction and dilution kinetics. It can be explained
      mechanistically without appealing to optimality principles. (2) The model
      explains the phenotypes of various mutants containing lesions in the regions
      encoding for the operator, repressor, and peripheral enzymes. A particularly
      striking phenotype is the "reversal of the diauxie" in which the wild-type and
      mutant strains consume the very same two substrates in opposite order. This
      phenotype is difficult to explain in terms of molecular mechanisms, such as
      inducer exclusion or CAP activation, but it turns out to be a natural consequence
      of the model. We show furthermore that the model is robust. The key property of
      the model, namely, the competitive dynamics of the enzymes, is preserved even if
      the model is modified to account for various regulatory mechanisms. Finally, the
      model has important implications for the problem of size regulation in
      development. It suggests that protein dilution may be the mechanism coupling
      patterning and growth.

PMID- 16989864
TI  - Encouraging compliance with graduated driver licensing restrictions.
AB  - PROBLEM: Although graduated driver licensing (GDL) programs have reduced the high
      crash rates for 16-and 17-year-old drivers, research suggests that some teenagers
      fail to comply with restrictions on nighttime driving and carrying passengers.
      METHOD: A program to encourage compliance with GDL restrictions and seat belt
      requirements was implemented in Guilford County, North Carolina. The program
      combined increased enforcement with a multi-faceted publicity campaign drawing
      attention to the enforcement activity. A comparison community was studied to
      assess whether changes over time could be reasonably attributed to the program.
      RESULTS: Several measures indicate that greater enforcement did occur in the
      intervention community and that teenagers perceived the increase. However, self
      reported data and direct observations of young drivers in the intervention and
      comparison communities showed the program resulted in only modest changes in
      compliance with GDL restrictions. DISCUSSION: The program put in place the
      mechanisms known to produce changes in driver behavior, but these may have been
      insufficient to alter the behavior of the minority of teenagers (and parents) who
      were not already complying with restrictions. However, the modest changes in
      young driver behavior plus the clear changes in both actual and perceived
      enforcement suggest that high visibility enforcement programs merit further use
      and evaluation in other communities, particularly those where compliance with GDL
      provisions is lower than in Guilford County.

PMID- 16989866
TI  - Modelling the effect of autotoxicity on density-dependent phytotoxicity.
AB  - An established method to separate resource competition from chemical interference
      is cultivation of monospecific, even-aged stands. The stands grow at several
      densities and they are exposed to homogenously spread toxins. Hence, the dose
      received by individual plants is inversely related to stand density. This results
      in distinguishable alterations in dose-response slopes. The method is often
      recommended in ecological studies of allelopathy. However, many plant species are
      known to release autotoxic compounds. Often, the probability of autotoxicity
      increases as sowing density increases. Despite this, the possibility of
      autotoxicity is ignored when experiments including monospecific stands are
      designed and when their results are evaluated. In this paper, I model
      mathematically how autotoxicity changes the outcome of dose-response slopes as
      different densities of monospecific stands are grown on homogenously phytotoxic
      substrata. Several ecologically reasonable relations between plant density and
      autotoxin exposure are considered over a range of parameter values, and
      similarities between different relations are searched for. The models indicate
      that autotoxicity affects the outcome of density-dependent dose-response
      experiments. Autotoxicity seems to abolish the effects of other phytochemicals in
      certain cases, while it may augment them in other cases. Autotoxicity may alter
      the outcome of tests using the method of monospecific stands even if the dose of
      autotoxic compounds per plant is a fraction of the dose of non-autotoxic
      phytochemicals with similar allelopathic potential. Data from the literature
      support these conclusions. A faulty null hypothesis may be accepted if the
      autotoxic potential of a test species is overlooked in density-response
      experiments. On the contrary, if test species are known to be non-autotoxic, the
      method of monospecific stands does not need fine-tuning. The results also suggest
      that the possibility of autotoxicity should be investigated in many density
      response bioassays that are made with even-aged plants, and that measure plant
      growth or germination.

PMID- 16989867
TI  - The origin of allometric scaling laws in biology.
AB  - The empirical rules relating metabolic rate and body size are described in terms
      of (i) a scaling exponent, which refers to the ratio of the fractional change in
      metabolic rate to a change in body size, (ii) a proportionality constant, which
      describes the rate of energy expenditure in an organism of unit mass. This
      article integrates the chemiosmotic theory of energy transduction with the
      methods of quantum statistics to propose a molecular mechanism which, in sharp
      contrast to competing models, explains both the variation in scaling exponents
      and the taxon-specific differences in proportionality constants. The new model is
      universal in the sense that it applies to unicellular organisms, plants and
      animals.

PMID- 16989868
TI  - Computational determination of refractive index distribution in the crystalline
      cones of the compound eye of Antarctic krill (Euphausia superba).
AB  - In order to understand how a compound eye channels light to the retina and forms
      an image, one needs to know the refractive index distribution in the crystalline
      cones. Direct measurements of the refractive indices require sections of fresh,
      unfixed tissue and the use of an interference microscope, but frequently neither
      is available. Using the eye of the Antarctic krill Euphausia superba (the main
      food of baleen whales) we developed a computational method to predict a likely
      refractive index distribution non-invasively from sections of fixed material
      without the need of an interference microscope. We used a computer model of the
      eye and calculated the most realistic spatial distribution of the refractive
      index gradient in the crystalline cone that would enable the eye to produce a
      sharp image on the retina. The animals are known to see well and on the basis of
      our computations we predict that for the eyes of the adult a maximum refractive
      index of 1.45-1.50 in the centre of the cone yields a better angular sensitivity
      and light absorption in a target receptor of the retina than if N(max) were 1.55.
      In juveniles with a narrower spatial separation between dioptric structures and
      retina, however, an N(max) of 1.50-1.55 gives a superior result. Our method to
      determine the most likely refractive index distribution in the cone without the
      need of fresh material and an interference microscope could be useful in the
      study of other invertebrate eyes that are known to possess good resolving power,
      but for a variety of reasons are not suitable for or will not permit direct
      refractive index measurements of their dioptric tissues to be taken.

PMID- 16989869
TI  - A modified Zeeman model for producing HRV signals and its application to ECG
      signal generation.
AB  - Developing a mathematical model for the artificial generation of
      electrocardiogram (ECG) signals is a subject that has been widely investigated.
      One of the challenges is to generate ECG signals with a wide range of waveforms,
      power spectra and variations in heart rate variability (HRV)--all of which are
      important indexes of human heart functions. In this paper we present a
      comprehensive model for generating such artificial ECG signals. We incorporate
      into our model the effects of respiratory sinus arrhythmia, Mayer waves and the
      important very low-frequency component in the power spectrum of HRV. We use a new
      modified Zeeman model for generating the time series for HRV, and a single cycle
      of ECG is produced by using a simple neural network. The importance of the work
      is the model's ability to produce artificial ECG signals that resemble
      experimental recordings under various physiological conditions. As such the model
      provides a useful tool to simulate and analyse the main characteristics of ECG,
      such as its power spectrum and HRV under different conditions. Potential
      applications of this model include using the generated ECG as a flexible signal
      source to assess the effectiveness of a diagnostic ECG signal-processing device.

PMID- 16989871
TI  - Intestinal absorption of hawthorn flavonoids--in vitro, in situ and in vivo
      correlations.
AB  - Our previous studies identified hyperoside (HP), isoquercitrin (IQ) and
      epicatechin (EC) to be the major active flavonoid components of the hawthorn
      phenolic extract from hawthorn fruits demonstrating inhibitory effect on in vitro
      Cu(+2)-mediated low density lipoproteins oxidation. Among these three hawthorn
      flavonoids, EC was the only one detectable in plasma after the oral
      administration of hawthorn phenolic extract to rats. The present study aims to
      investigate the intestinal absorption mechanisms of these three hawthorn
      flavonoids by in vitro Caco-2 monolayer model, rat in situ intestinal perfusion
      model and in vivo pharmacokinetics studies in rats. In addition, in order to
      investigate the effect of the co-occurring components in hawthorn phenolic
      extract on the intestinal absorption of these three major hawthorn flavonoids,
      intestinal absorption transport profiles of HP, IQ and EC in forms of individual
      pure compound, mixture of pure compounds and hawthorn phenolic extract were
      studied and compared. The observations from in vitro Caco-2 monolayer model and
      in situ intestinal perfusion model indicated that all three studied hawthorn
      flavonoids have quite limited permeabilities. EC and IQ demonstrated more
      extensive metabolism in the rat in situ intestinal perfusion model and in vivo
      study than in Caco-2 monolayer model. Moreover, results from the Caco-2 monolayer
      model, rat in situ intestinal perfusion model as well as the in vivo
      pharmacokinetics studies in rats consistently showed that the co-occurring
      components in hawthorn phenolic extract might not have significant effect on the
      intestinal absorption of the three major hawthorn flavonoids studied.

PMID- 16989870
TI  - The ascochlorin derivative, AS-6, inhibits TNF-alpha-induced adhesion molecule
      and chemokine expression in rat vascular smooth muscle cells.
AB  - Vascular inflammation induced by the proinflammatory cytokine/NF-kappaB pathway
      is one of the key mechanisms in the development of atherosclerosis. Peroxisome
      proliferators-activated receptor-gamma (PPARgamma) plays an important role in the
      prevention of arterial inflammation and formation of atherogenesis. Herein we
      examine the effects of a newly identified synthetic PPARgamma ligand, ascochlorin
      6 (AS-6), on TNF-alpha-stimulated NF-kappaB activity and inflammatory molecule
      expression in vascular smooth muscle cells (VSMCs). AS-6 successfully inhibited
      TNF-alpha-stimulated NF-kappaB activity and inflammatory molecule expression,
      including vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic
      protein-1 (MCP-1), and fractalkine (CX3CL1). Transient transfection with an [NF
      kappaB]x4 luciferase reporter construct showed that AS-6 inhibition of TNF-alpha
      stimulated NF-kappaB activation was PPARgamma-dependent. The effects of AS-6 on
      TNF-alpha-stimulated VCAM-1 and CX3CL1 expression were abolished in cells
      transfected with an adenovirus expressing dominant-negative PPARgamma and in
      cells treated with a PPARgamma specific inhibitor, GW9662, confirming again that
      the anti-inflammatory effect of AS-6 was PPARgamma-dependent. The inhibitory
      effects of AS-6 on TNF-alpha-stimulated inflammatory gene expression and NF
      kappaB activation were more potent than those of rosiglitazone and pioglitazone.
      This study shows that AS-6 reduces the inflammatory response to TNF-alpha in
      VSMCs. The data suggest the possibility that AS-6 can be used to prevent the
      development and progression of atherosclerosis.

PMID- 16989872
TI  - Mutagenic effect of cadmium on tetranucleotide repeats in human cells.
AB  - Cadmium is a human carcinogen that affects cell proliferation, apoptosis and DNA
      repair processes that are all important to carcinogenesis. We previously
      demonstrated that cadmium inhibits DNA mismatch repair (MMR) in yeast cells and
      in human cell-free extracts (H.W. Jin, A.B. Clark, R.J.C. Slebos, H. Al-Refai,
      J.A. Taylor, T.A. Kunkel, M.A. Resnick, D.A. Gordenin, Cadmium is a mutagen that
      acts by inhibiting mismatch repair, Nat. Genet. 34 (3) (2003) 326-329), but
      cadmium also inhibits DNA excision repair. For this study, we selected a panel of
      three hypermutable tetranucleotide markers (MycL1, D7S1482 and DXS981) and
      studied their suitability as readout for the mutagenic effects of cadmium. We
      used a clonal derivative of the human fibrosarcoma cell line HT1080 to assess
      mutation levels in microsatellites after cadmium and/or N-methyl-N-nitro-N
      nitrosoguanidine (MNNG) exposure to study effects of cadmium in the presence or
      absence of base damage. Mutations were measured in clonally expanded cells
      obtained by limiting dilution after exposure to zero dose, 0.5 microM cadmium, 5
      nM MNNG or a combination of 0.5 microM cadmium and 5 nM MNNG. Exposure of HT1080
      C1 to cadmium led to statistically significant increases in microsatellite
      mutations, either with or without concurrent exposure to MNNG. A majority of the
      observed mutant molecules involved 4-nucleotide shifts consistent with DNA
      slippage mutations that are normally repaired by MMR. These results provide
      evidence for the mutagenic effects of low, environmentally relevant levels of
      cadmium in intact human cells and suggest that inhibition of DNA repair is
      involved.

PMID- 16989873
TI  - Acquired amnesia in childhood: a single case study.
AB  - We report the case of C.L., an 8-year-old child who, following the surgical
      removal of an ependymoma from the left cerebral ventricle at the age of 4 years,
      developed significant difficulties in retaining day-to-day events and
      information. A thorough neuropsychological analysis documented in C.L. a severe
      anterograde amnesic syndrome, characterised by normal short-term memory, but poor
      performance on episodic long-term memory tests. In particular, C.L. demonstrated
      virtually no ability to recollect new verbal information several minutes after
      the presentation. As for semantic memory, C.L. demonstrated general semantic
      competencies, which, depending on the test, ranged from the level of a 6-year-old
      girl to a level corresponding to her actual chronological age. Finding a patient
      who, despite being severely impaired in the ability to recollect new episodic
      memories, still demonstrates at least partially preserved abilities to acquire
      new semantic knowledge suggests that neural circuits implicated in the
      memorisation of autobiographical events and factual information do not overlap
      completely. This case is examined in the light of growing literature concerned
      with the dissociation between episodic and semantic memory in childhood amnesia.

PMID- 16989874
TI  - Support for an auto-associative model of spoken cued recall: evidence from fMRI.
AB  - Cued recall and item recognition are considered the standard episodic memory
      retrieval tasks. However, only the neural correlates of the latter have been
      studied in detail with fMRI. Using an event-related fMRI experimental design that
      permits spoken responses, we tested hypotheses from an auto-associative model of
      cued recall and item recognition [Chappell, M., & Humphreys, M. S. (1994). An
      auto-associative neural network for sparse representations: Analysis and
      application to models of recognition and cued recall. Psychological Review, 101,
      103-128]. In brief, the model assumes that cues elicit a network of phonological
      short term memory (STM) and semantic long term memory (LTM) representations
      distributed throughout the neocortex as patterns of sparse activations. This
      information is transferred to the hippocampus which converges upon the item
      closest to a stored pattern and outputs a response. Word pairs were learned from
      a study list, with one member of the pair serving as the cue at test. Unstudied
      words were also intermingled at test in order to provide an analogue of yes/no
      recognition tasks. Compared to incorrectly rejected studied items (misses) and
      correctly rejected (CR) unstudied items, correctly recalled items (hits) elicited
      increased responses in the left hippocampus and neocortical regions including the
      left inferior prefrontal cortex (LIPC), left mid lateral temporal cortex and
      inferior parietal cortex, consistent with predictions from the model. This
      network was very similar to that observed in yes/no recognition studies,
      supporting proposals that cued recall and item recognition involve common rather
      than separate mechanisms.

PMID- 16989875
TI  - Monoaminergic system lesions increase post-sigh respiratory pattern disturbance
      during sleep in rats.
AB  - Monoamines are important regulators of behavioral state and respiratory pattern,
      and the impact of monoaminergic control during sleep is of particular interest
      for the stability of breathing regulation. The aim of this study was to test the
      effects of systemically induced chemical lesions to noradrenergic and
      serotonergic efferent systems, on the expression of sleep-wake states, pontine
      wave activity, and sleep-related respiratory pattern and its variability. In
      chronically instrumented male adult Sprague-Dawley rats we lesioned noradrenergic
      terminal axonal branches by a single intraperitoneal dose of DSP-4 (N-(2
      chloroethyl)-N-ethyl-2-brombenzilamine; 50 mg/kg, i.p.), and serotonergic axonal
      terminals by two intraperitoneal doses, 24 h apart, of PCA (p-chloroamphetamine;
      6 mg/kg, i.p.). In each animal, we recorded sleep, pontine waves (P-waves) and
      breathing at baseline, following sham injection, and every week for 5 weeks
      following injection of either systemic neurotoxin. Distinct responses were
      observed to the two lesions. DSP-4 lesions were associated with a trend toward
      increased NREM sleep (p < 0.06), decreased wakefulness (p < 0.05) and increased
      respiratory tidal volume during NREM (p = 0.0002) and REM (p = 0.0001) sleep with
      respect to baseline. None of these effects, however, were observed during the
      first 14 days after injection. No significant changes were observed in the
      frequency of apneas or sighs, nor in the coupling between these two, at any time
      after DSP-4 injection. Conversely, selective serotonergic lesion by PCA produced
      no change in the baseline respiratory frequency or tidal volume during sleep or
      wakefulness, nor was the expression of Wake, NREM or REM sleep affected. Instead,
      PCA injection resulted in a sustained increase in the frequency and duration of
      post-sigh apneas (PS) during NREM sleep (p = 0.002). This reflected increased
      coupling between sighs and apneas, because neither the frequency nor the
      amplitude of spontaneous sighs was altered by PCA.

PMID- 16989876
TI  - Basal metabolic rate and organ size in Brandt's voles (Lasiopodomys brandtii):
      Effects of photoperiod, temperature and diet quality.
AB  - This study examined the effects of photoperiod (long day [16 Light:8 Dark] and
      short day [8 Light:16 Dark]), temperature (cold [5 degrees C] and warm [23
      degrees C]), and diet quality (high-fiber diet [36% neutral-detergent fiber
      (NDF)] and low-fiber diet [23% NDF]) on basal metabolic rate (BMR), digestible
      energy intake, and organ size in the Brandt's vole (Lasiopodomys brandtii). Cold
      increased BMR and showed a significant interaction with diet quality. Cold and
      short photoperiod increased intake of food and digestible energy. The high-fiber
      diet increased food intake, but decreased digestibility, and had no effects on
      digestible energy intake. Voles housed in the cold had heavier liver, kidneys and
      gastrointestinal segments but a lighter carcass. Segments of the gastrointestinal
      tract tended to be heavier when voles were fed the high-fiber diet. Voles housed
      in short photoperiod had lighter heart and kidneys but heavier gut segments. With
      the effects of body mass on BMR and organs was removed, BMR was significantly
      related to the dry mass of heart, liver, kidneys and cecum. Digestible energy
      intake was significantly related to the dry mass of kidneys and stomach. These
      significant relationships were also detected after removing the effects of body
      mass, temperature, photoperiod and diet quality. There was also a significant
      correlation between BMR and digestible energy intake. Our results suggest that
      variations in BMR reflected the evolution of metabolic machinery that induces
      higher energy intakes. The data also support the assimilation capacity model of
      endothermy.

PMID- 16989878
TI  - Metabolic changes in Arabidopsis thaliana expressing the feedback-resistant
      anthranilate synthase alpha subunit gene OASA1D.
AB  - Anthranilate synthase (AS) is a key enzyme in tryptophan (Trp) biosynthesis.
      Metabolic changes in transgenic Arabidopsis plants expressing the feedback
      resistant anthranilate synthase alpha subunit gene OASA1D were investigated with
      respect to Trp synthesis and effects on secondary metabolism. The Trp content
      varied depending on the transgenic line, with some lines showing an approximately
      200-fold increase. The levels of AS activity in crude extracts from the
      transgenic lines were comparable to those in the wild type. On the other hand,
      the enzyme prepared from the lines accumulating high levels of Trp showed a
      relaxed feedback sensitivity. The AS activity, determined in the presence of 50
      microM L-Trp, correlated well with the amount of free Trp in the transgenic
      lines, indicating the important role of feedback inhibition in control of Trp
      pool size. In Arabidopsis, Trp is a precursor of multiple secondary metabolites,
      including indole glucosinolates and camalexin. The amount of indol-3-ylmethyl
      glucosinolate (I3 M) in rosette leaves of the high-Trp accumulating lines was 1.5
      to 2.1-fold greater than that in wild type. The treatment of the leaves with
      jasmonic acid resulted in a more pronounced accumulation of I3 M in the high-Trp
      accumulating lines than in wild type. The induction of camalexin formation after
      the inoculation of Alternaria brassicicola was not affected by the accumulation
      of a large amount of Trp. The accumulation of constitutive phenylpropanoids and
      flavonoids was suppressed in high-Trp accumulating lines, while the amounts of
      Phe and Tyr increased, thereby indicating an interaction between the Trp branch
      and the Phe and Tyr branch in the shikimate pathway.

PMID- 16989879
TI  - Evolutionarily stable germination strategies with time-correlated yield.
AB  - We investigate the effect of auto-correlated yield on the evolutionarily stable
      germination fraction of dormant seeds. By using both analytics and numerics, we
      first show that in a regime of small fluctuations a positive correlation reduces
      dormancy and a negative correlation enhances dormancy. By extending the numerical
      analysis we also show that in the regime of large fluctuations a more complex
      picture emerges where also negative correlations can reduce dormancy.

PMID- 16989880
TI  - Inhibition of nucleotide excision repair (NER) by microcystin-LR in CHO-K1 cells.
AB  - Microcystin-LR (MC-LR), a potent inhibitor of PP1 and PP2A protein phosphatases,
      is related to tumor promotion and initiation. Although the genotoxic properties
      of this toxin have been extensively investigated with a variety of non-mammalian
      and mammalian test systems, the existing results are contradictory. Based on our
      previous results regarding the impact of MC-LR on the processes of DNA repair we
      decided to examine in greater detail its effect on the capacity of nucleotide
      excision repair (NER). CHO-K1 cells were pre-treated with increasing doses of MC
      LR (1, 10 and 20 microg/ml) and then exposed to UV radiation (25 J/m(2)).
      Apoptosis was analyzed to exclude the possibility of false positive results in
      the comet assay. The results suggest that MC-LR targets the nucleotide excision
      repair mechanisms by interference with the incision/excision phase as well as the
      rejoining phase of NER and leads to an increased level of UV-induced cytogenetic
      DNA damage in CHO-K1 cells.

PMID- 16989881
TI  - Study of 1-3-2 type piezoelectric composite transducer array.
AB  - Based on a new structure of precise location and decoupling between the
      transducer elements, high frequency underwater transmission transducer arrays
      with 4 elements and 8 elements serried uniform linear array were studied, using
      novel 1-3-2 type piezoelectric composite as the sensing material. There are
      ceramic framework supports in the transverse and longitudinal directions in 1-3-2
      type piezoelectric composite structure; the transducer is free from the influence
      of outside mechanical impact and the environment temperature change. Transducer
      and array samples have been designed, fabricated and measured. The resonant
      frequency is 150 kHz, resonant transmission response greater than 160 dB, and
      bandwidth is from 140 kHz to 160 kHz. The results indicate that, the transducer
      array has wide bandwidth, high sensitivity, stabile performance, and good
      coherence.

PMID- 16989882
TI  - 3D Gabor analysis of transient waves propagating along an AT cut quartz disk.
AB  - Laser detection methods allow the investigation of ultrasonic transient phenomena
      in both space and time dimensions. Used for the experimental investigation of
      surface wave propagation along a 2D surface, laser ultrasonic leads to three
      dimensional (3D) space-time signal collections. The classical high resolution
      signal processing methods or 3D Fourier Transforms can be used in order to
      extract the wave propagation information, however these methods are not adapted
      for identifying where and when the waves are generated. In order to quantify
      these transient aspects in the space-time-wave number-frequency domains, the 3D
      Gabor transform is introduced. The 3D Gabor transform properties are presented.
      The potential of the 3D Gabor for the identification of the local and transient
      complex wave numbers is illustrated on the propagation of surface waves on a
      piezoelectric quartz (AT cut, 6 MHz). In this experimental study, the quartz is
      excited by a voltage pulse and the quartz surface is scanned by a laser
      vibrometer. The 3D Gabor analysis shows that the circular electrodes borders
      generate anti-phase surface waves that propagates outside the electrodes, with a
      strong energy contribution in the low frequency domain (<1 MHz). The transient
      analysis also points out, for higher frequencies, where the surface waves are
      generated and how they propagate with respect of both to the geometry of the
      electrodes and the crystallographic axis of the quartz. These results confirm the
      theoretical modal analysis and provide new knowledge about the key role played by
      the electrodes border. This will allow the optimization of the electrodes shape
      in order to design low frequency Lamb wave sensors.

PMID- 16989883
TI  - Characterization of Marburg virus glycoprotein in viral entry.
AB  - One major determinant of host tropism for filoviruses is viral glycoprotein (GP),
      which is involved in receptor binding and viral entry. Compared to Ebola GP
      (EGP), Marburg GP (MGP) is less well characterized in viral entry. In this study,
      using a human immunodeficiency virus-based pseudotyped virus as a surrogate
      system, we have characterized the role of MGP in viral entry. We have shown that
      like EGP, the mucin-like region of MGP (289-501) is not essential for virus
      entry. We have developed a viral entry interference assay for filoviruses, and
      using this assay, we have demonstrated that transfection of EGP or MGP in target
      cells can interfere with EGP/HIV and MGP/HIV pseudotyped virus entry in a dose
      dependent manner. These results are consistent with the notion that Ebola and
      Marburg viruses use the same or a related host molecule(s) for viral entry.
      Substitutions of the non-conserved residues in MGP1 did not impair MGP-mediated
      viral entry. Unlike that of EGP1, individual substitutions of many conserved
      residues of MGP1 exerted severe defects in MGP expression, incorporation to HIV
      virions, and thus its ability to mediate viral entry. These results indicate that
      MGP is more sensitive to substitutions of the conserved residues, suggesting that
      MGP may fold differently from EGP.

PMID- 16989885
TI  - G-protein alpha and beta-gamma subunits interact with conformationally distinct
      signaling states of rhodopsin.
AB  - Light activated rhodopsin interacts with domains on all three subunits of
      transducin. Two of these domains, the C-terminal regions of the alpha and gamma
      subunits mimic the ability of transducin to stabilize the active conformation of
      rhodopsin, metarhodopsin II, but display different roles in transducin activation
      process. Whether the interactions are with the same or different complimentary
      sites on Meta II is unknown. We have used chemo-selective thioalkylation of
      rhodopsin and UV/visible spectroscopy to show that interactions with transducin C
      terminal domains can be selectively disrupted. These data provide evidence that
      formal structural determinants on Meta II for these domains of transducin are
      different. In a set of complimentary experiments we examined the reactivity of
      Meta II species produced in the presence of the Gtalpha and Gtgamma subunit
      peptides to hydroxylamine. Analysis of the rates of Meta II decay confirms that
      the conformational states of Meta II when bound to Gtalpha and Gtbetagamma
      represent distinct signaling states of rhodopsin.

PMID- 16989884
TI  - Palmitylation of cone opsins.
AB  - Palmitylation is a widespread modification in G-protein-coupled receptors and
      often a dynamic process. In rhodopsins, palmitylation is static on C322/C323.
      Red/green (M/LWS) cone opsins have no cysteines at corresponding positions and no
      palmitylation. Blue (SWS2) cone opsins have a single corresponding cysteine and
      mass spectrometric analysis showed partial palmitylation of salamander SWS2 cone
      opsin. Ultraviolet (SWS1) cone opsins have one corresponding cysteine, but only
      unpalmitylated opsin was observed for mouse and salamander. The results show that
      the static palmitylation found on rhodopsin is not found on cone opsins and
      suggest the possibility of an unidentified role for opsin palmitylation in cones.

PMID- 16989886
TI  - Life cycle assessment of a coupled solar photocatalytic-biological process for
      wastewater treatment.
AB  - A comparative life cycle assessment (LCA) of two solar-driven advanced oxidation
      processes, namely heterogeneous semiconductor photocatalysis and homogeneous
      photo-Fenton, both coupled to biological treatment, is carried out in order to
      identify the environmentally preferable alternative to treat industrial
      wastewaters containing non-biodegradable priority hazardous substances. The study
      is based on solar pilot plant tests using alpha-methyl-phenylglycine as a target
      substance. The LCA study is based on the experimental results obtained, along
      with data from an industrial-scale plant. The system under study includes
      production of the plant infrastructure, chemicals, electricity, transport of all
      these materials to the plant site, management of the spent catalyst by transport
      and landfilling, as well as treatment of the biodegradable effluent obtained in a
      conventional municipal wastewater treatment plant, and excess sludge treatment by
      incineration. Nine environmental impact categories are included in the LCA:
      global warming, ozone depletion, human toxicity, freshwater aquatic toxicity,
      photochemical ozone formation, acidification, eutrophication, energy consumption,
      and land use. The experimental results obtained in the pilot plant show that
      solar photo-Fenton is able to obtain a biodegradable effluent much faster than
      solar heterogeneous photocatalysis, implying that the latter would require a much
      larger solar collector area in an industrial application. The results of the LCA
      show that, an industrial wastewater treatment plant based on heterogeneous
      photocatalysis involves a higher environmental impact than the photo-Fenton
      alternative, which displays impact scores 80-90% lower in most impact categories
      assessed. These results are mainly due to the larger size of the solar collector
      field needed by the plant.

PMID- 16989887
TI  - Characterization of two new multiforms of Trametes pubescens laccase.
AB  - Electrochemical properties of two multiforms of laccase from Trametes pubescens
      basidiomycete (LAC1 and LAC2) have been studied. The standard redox potentials of
      the T1 sites of the enzymes were found to be 746 and 738 mV vs. NHE for LAC1 and
      LAC2, respectively. Bioelectroreduction of oxygen based on direct electron
      transfer between each of the two forms of Trametes pubescens laccase and
      spectrographic graphite electrodes has been demonstrated and studied. It is
      concluded that the T1 site of laccase is the first electron acceptor, both in
      solution (homogeneous case) and when the enzymes are adsorbed on the surface of
      the graphite electrode (heterogeneous case). Thus, the previously proposed
      mechanism of oxygen bioelectroreduction by adsorbed fungal laccase was
      additionally confirmed using two forms of the enzyme. Moreover, the assumed need
      for extracellular laccase to communicate directly and electronically with a solid
      matrix (lignin) in the course of lignin degradation is discussed. In summary, the
      possible roles of multiforms of the enzyme based on their electrochemical,
      biochemical, spectral, and kinetic properties have been suggested to consist in
      broadening of the substrate specificity of the enzyme, in turn yielding the
      possibility to dynamically regulate the process of lignin degradation according
      to the real-time survival needs of the organism.

PMID- 16989888
TI  - Reproductive toxicity of trenbolone acetate in embryonically exposed Japanese
      quail.
AB  - This study was conducted to assess the effects of a one time embryonic exposure
      to trenbolone acetate on reproductive development and function in Japanese quail
      (Coturnix japonica). Embryos were exposed to either 0.05, 0.5, 5, or 50microg
      trenbolone or a sesame oil vehicle control at embryonic day 4. Onset of puberty,
      gonadal histopathology, sperm motility, cloacal gland size, and male copulatory
      behavior were assessed in adults. Trenbolone delayed onset of puberty in males,
      inhibited cloacal gland development, and reduced male reproductive behaviors.
      Industry laboratories have shown trenbolone acetate to be non-teratogenic in
      mammalian studies. Our study, however, shows that this one time in ovo exposure
      delayed onset of puberty in and suppressed adult copulatory behavior in quail
      males. These results suggest that this one time embryonic exposure to trenbolone
      may have disrupted development of either the central nervous system or the
      hypothalamic-pituitary-gonadal axis. This is the first study to demonstrate a
      demasculinizing effect on copulatory behavior in Japanese quail from embryonic
      exposure to a non-aromatizable androgenic chemical. More studies are needed to
      determine the mechanisms behind the observed effects.

PMID- 16989889
TI  - PCBs, PCNs and PBDEs in sediments and mussels from Qingdao coastal sea in the
      frame of current circulations and influence of sewage sludge.
AB  - Influence of current circulation and sewage sludge on spatial distributions of
      polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs), and
      polybrominated diphenyl ethers (PBDEs) in sediments and mussels from the Qingdao
      coastal sea were investigated. Total concentrations of PCBs, PCNs and PBDEs in
      sediments ranged 6.5-32.9, 0.2-1.2, and 0.1-5.5 ngg(-1) dry wt, respectively. The
      maximum concentrations were all found near the Haibo River mouth, affected by
      sewage sludge input from the river. Under the current system in Jiaozhou Bay the
      organic pollutants were subject to deposit on the east side of the bay and
      trapped inside the bay. Sewage sludge was an important source of PCBs, PCNs and
      PBDEs in the bay and exponentially magnified the enrichment of PCBs. On the other
      hand, the congener profiles of PCBs in sediments outside the bay may signify an
      atmospheric source of PCBs. Total Concentrations of PCBs, PCNs and PBDEs in
      mussels were 61.4-88.6, 9.0, and 13.8 ngg(-1)lipid, respectively. Mussels
      enriched significantly PCBs, PCNs and PBDEs relative to the sediments. The total
      toxicity equivalent quantities (TEQs) of PCNs in mussels were generally lower
      than that of PCBs. The fluxes of the total PCBs and their TEQs have been
      decreased steadily since 1950s. The lower chlorinated/brominated congeners of
      PCNs and PBDEs may exhibit a greater tendency due to less lipophilic and thus a
      greater probability of being affected by the current circulation in the bay.

PMID- 16989890
TI  - Combined biological and photocatalytic treatment for the mineralization of phenol
      in water.
AB  - Phenol is degraded by biological treatment, however mineralization requires long
      time. To decrease the time and operational cost necessary for the mineralization
      of phenol, an optimum operation condition of the combined biological
      photocatalytical treatment was investigated. The mineralization of phenol (50 mg
      l(-1)) was conducted in a flow-type biomembrane tank combined with a batch-type
      TiO2-suspended photocatalytic reactor. Phenol was degraded biologically to the
      concentration of 6.8 mg l(-1), an effective concentration for further
      photocatalytic treatment. After the biological treatment, the biotreated phenol
      was treated photocatalytically to complete the mineralization of phenol. The
      combined treatment shortened the mineralization time compared to the biological
      treatment and electric cost compared to the photocatalytic treatment only. The
      combined treatment may be suitable for a short-time mineralization of phenol in
      wastewater.

PMID- 16989892
TI  - Isotope evidence of palaeorecharge and palaeoclimate in the deep confined
      aquifers of the Chad Basin, NE Nigeria.
AB  - Groundwaters from the Quaternary and Continental Terminal Formations in the
      Nigeria sector of the Chad Sedimentary Basin (CSB) together with rain and surface
      waters have been chemically and isotopically analyzed in order to investigate
      sources and ages of waters, possible modern renewal and mixing of the deep
      groundwaters, and to infer palaeoclimate incidences. Most of the waters are
      slightly to moderately mineralized and are of Na-HCO(3) type induced mainly by Na
      feldspar weathering and ion exchange reactions. The wide range of the delta(18)O
      and delta(2)H values and (3)H contents in the upper aquifer indicate
      replenishment with modern meteoric water. However, the deep system (middle and
      lower aquifers) with a narrow range of depleted stable isotope values and low
      (14)C activities indicates that these waters have a palaeometeoric origin. The
      period of infiltration was within the humid and cooler period (35 to 40 ka BP)
      prior to the Last Glacial Maximum. In addition, the isotope compositions of the
      deep system show no mixing with modern waters. These results are in agreement
      with other palaeorecord studies in the Sahel zone during this period.

PMID- 16989893
TI  - Fluorescent pseudomonads occurring in Macrotermes subhyalinus mound structures
      decrease Cd toxicity and improve its accumulation in sorghum plants.
AB  - Cd-tolerant bacterial strains of fluorescent pseudomonads, mostly belonging to
      Pseudomonas monteillii, were isolated from termite mound soil (Macrotermes
      subhyalinus, a litter-forager and fungus-growing termite), in a Sudanese shrubby
      savanna, Burkina Faso. Such large mounds appeared as sites of great bacterial
      diversity and could be considered as hot spots of metal-tolerant fluorescent
      pseudomonads. Microbial isolates were inoculated to Sorghum plants (S. bicolor)
      in glasshouse experiments with soil amended with CdCl(2) (560 mg Cd kg(-1) soil).
      Microbial functional diversity was assessed at the end of the experiment by
      measurement of in situ patterns of catabolic potentials. All the bacteria
      isolates significantly improved the shoot and total biomass of sorghum plants
      compared to the control. Results concerning root biomass were not significant
      with some strains. Arbuscular mycorrhiza (AM) was greatly reduced by CdCl(2)
      amendment, and fluorescent pseudomonad inoculation significantly increased AM
      colonisation in the contaminated soil. The bacterial inoculation significantly
      improved Cd uptake by sorghum plants. Measurement of catabolic potentials on 16
      substrates showed that the microbial communities were different according to the
      soil amendment. Soils samples inoculated with pseudomonad strains presented a
      higher use of ketoglutaric and hydroxybutiric acids, as opposed to fumaric acid
      in soil samples not inoculated. It is suggested that fluorescent pseudomonads
      could act indirectly in such metabolic processes by involving a lower rate of
      degradation of citric acid, in line with the effect of small organic acid on
      phytoextraction of heavy metals from soil. This is a first contribution to
      bioremediation of metal-contaminated sites with soil-to-plant transfer, using
      termite built structures. Further data are required on the efficiency of the
      bacterial strains isolated and on the processes involved.

PMID- 16989894
TI  - Elemental concentrations and metal bioaccessibility in UK household dust.
AB  - Concentrations of metals and C, H and N have been determined in 32 household dust
      samples collected from four regions of the UK. For a given metal, total
      concentrations (available to aqua regia digestion) were highly variable, but
      geometric mean concentrations (in mug g(-1): Al=7950; Cd=1.2; Cu=301; Fe=8740;
      Mn=524; Ni=53.1; Pb=150; Sn=23.9; Zn=622) were, in general, consistent with
      equivalent values reported in the contemporary literature for a number of
      locations worldwide. Of the metals studied, Cd, Cu, Pb, Sn and Zn exhibited
      greatest enrichment in the household environment relative to their respective
      crustal abundances. Bioaccessibility of metals in dust, evaluated using a
      simulated gastric solution (pepsin in dilute HCl), ranged from about 10% of total
      metal for Sn to about 80% for Cu, Pb and Zn, indicating that enrichment alone is
      not necessarily a good proxy for assessing metal exposure or impact.
      Concentrations of C, H and N in household dust, determined combustiometrically,
      ranged from 11% to 46.2%, 1.5% to 7.0% and 1.0% to 8.5%, respectively. Carbon to
      hydrogen ratios of dust samples were relatively uniform (arithmetic mean 7.3;
      rsd<10%), reflecting the similarity of C:H ratios in various source materials. In
      contrast, C:N ratios were highly variable (arithmetic mean 8.5; rsd>40%),
      reflecting the variability of C:N ratios in source materials (e.g. protein=2.1;
      soil humics=14; lignin=78). Lack of correlation between metal concentrations and
      concentrations or ratios of C, H and N was attributed to the heterogeneous
      distribution of metal concentrations among the array of internal and external
      sources of household dust.

PMID- 16989895
TI  - Overview of experimental studies of biological effects of medical ultrasound
      caused by gas body activation and inertial cavitation.
AB  - Ultrasound exposure can induce bioeffects in mammalian tissue by the nonthermal
      mechanism of gas body activation. Pre-existing bodies of gas may be activated
      even at low-pressure amplitudes. At higher-pressure amplitudes, violent
      cavitation activity with inertial collapse of microbubbles can be generated from
      latent nucleation sites or from the destabilization of gas bodies. Mechanical
      perturbation at the activation sites leads to biological effects on nearby cells
      and structures. Shockwave lithotripsy was the first medical ultrasound
      application for which significant cavitational bioeffects were demonstrated in
      mammalian tissues, including hemorrhage and injury in the kidney. Lithotripter
      shockwaves can also cause hemorrhage in lung and intestine by activation of pre
      existing gas bodies in these tissues. Modern diagnostic ultrasound equipment
      develops pressure amplitudes sufficient for inertial cavitation, but the living
      body normally lacks suitable cavitation nuclei. Ultrasound contrast agents (UCAs)
      are suspensions of microscopic gas bodies created to enhance the echogenicity of
      blood. Ultrasound contrast agent gas bodies also provide nuclei for inertial
      cavitation. Bioeffects from contrast-aided diagnostic ultrasound depend on
      pressure amplitude, UCA dose, dosage delivery method and image timing parameters.
      Microvascular leakage, capillary rupture, cardiomyocyte killing, inflammatory
      cell infiltration, and premature ventricular contractions have been reported for
      myocardial contrast echocardiography with clinical ultrasound machines and
      clinically relevant agent doses in laboratory animals. Similar bioeffects have
      been reported in intestine, skeletal muscle, fat, lymph nodes and kidney. These
      microscale bioeffects could be induced unknowingly in diagnostic examinations;
      however, the medical significance of bioeffects of diagnostic ultrasound with
      contrast agents is not yet fully understood in relation to the clinical setting.

PMID- 16989896
TI  - Physiology and gene regulation of the brain NPY Y1 receptor.
AB  - Neuropeptide Y (NPY) is one of the most prominent and abundant neuropeptides in
      the mammalian brain where it interacts with a family of G-protein coupled
      receptors, including the Y(1) receptor subtype (Y(1)R). NPY-Y(1)R signalling
      plays a prominent role in the regulation of several behavioural and physiological
      functions including feeding behaviour and energy balance, sexual hormone
      secretion, stress response, emotional behaviour, neuronal excitability and
      ethanol drinking. Y(1)R expression is regulated by neuronal activity and
      peripheral hormones. The Y(1)R gene has been isolated from rodents and humans and
      it contains multiple regulatory elements that may participate in the regulation
      of its expression. Y(1)R expression in the hypothalamus is modulated by changes
      in energetic balance induced by a wide variety of conditions (fasting, pregnancy,
      hyperglycaemic challenge, hypophagia, diet induced obesity). Estrogens up
      regulate responsiveness to NPY to stimulate preovulatory GnRH and gonadotropin
      surges by increasing Y(1)R gene expression both in the hypothalamus and the
      pituitary. Y(1)R expression is modulated by different kinds of brain insults,
      such as stress and seizure activity, and alteration in its expression may
      contribute to antidepressant action. Chronic modulation of GABA(A) receptor
      function by benzodiazepines or neuroactive steroids also affects Y(1)R expression
      in the amygdala, suggesting that a functional interaction between the GABA(A)
      receptor and Y(1)R mediated signalling may contribute to the regulation of
      emotional behaviour. In this paper, we review the state of the art concerning
      Y(1)R function and gene expression, including our personal contribution to many
      of the subjects mentioned above.

PMID- 16989897
TI  - A multicellular spheroid array to realize spheroid formation, culture, and
      viability assay on a chip.
AB  - We describe a novel multicellular spheroid culture system that facilitates the
      easy preparation and culture of a spheroid microarray for the long-term
      monitoring of cellular activity. A spheroid culture device with an array of
      pyramid-like microholes was constructed in a silicon chip that was equipped with
      elastomeric microchannels. A cell suspension was introduced via the microfluidic
      channel into the microstructure that comprised silicon microholes and elastomeric
      microwells. A single spheroid can be formed and localized precisely within each
      microstructure. Since the culture medium could be replaced via the microchannels,
      a long-term culture (of approximately 2 weeks) is available on the chip.
      Measurement of albumin production in the hepatoma cell line (HepG2) showed that
      the liver-specific functions were maintained for 2 weeks. Based on the cellular
      respiratory activity, the cellular viability of the spheroid array on the chip
      was evaluated using scanning electrochemical microscopy. Responses to four
      different chemical stimulations were simultaneously detected on the same chip,
      thus demonstrating that each channel could be evaluated independently under
      various stimulation conditions. Our spheroid culture system facilitated the
      understanding of spheroid formation, culture, and viability assay on a single
      chip, thus functioning as a useful drug-screening device for cancer and liver
      cells.

PMID- 16989898
TI  - First molecular cloning and characterisation of caspase-9 gene in fish and its
      involvement in a gram negative septicaemia.
AB  - Caspase-9 is an initiator caspase in the apoptotic process whose function is to
      activate effector caspases that are downstream in the mitochondrial pathway of
      apoptosis. This work reports for the first time the complete sequencing and
      characterisation of caspase-9 in fish. A 1924bp cDNA of sea bass caspase-9 was
      obtained, consisting of 1308bp open reading frame coding for 435 amino acids,
      199bp of the 5'-UTR and 417bp of the 3'-UTR including a canonical polyadenilation
      signal 10 nucleotides upstream the polyadenilation tail. The sequence retains the
      pentapeptide active-site motif (QACGG) and the putative cleavage sites at
      Asp(121), Asp(325) and Asp(343). The sequence of sea bass caspase-9 exhibits a
      very close homology to the sequences of caspase-9 from other vertebrates,
      particularly with the putative caspases-9 of Danio rerio and Tetraodon
      nigroviridis (77.5 and 75.4% similarity, respectively), justifying the fact that
      the phylogenetic analysis groups these species together with sea bass. The sea
      bass caspase-9 gene exists as a single copy gene and is organised in 9 introns
      and 10 exons. The sea bass caspase-9 showed a basal expression in all the organs
      analysed, although weaker in spleen. The expression of sea bass caspase-9 in the
      head kidney of sea bass infected with the Photobacterium damselae ssp. piscicida
      (Phdp) strain PP3, showed increased expression from 0 to 12h returning to control
      levels at 24h. Caspase-9 activity was detected in Phdp infected sea bass head
      kidney from 18 to 48h post-infection, when the fish were with advanced
      septicaemia.

PMID- 16989899
TI  - Protein kinase R, IkappaB kinase-beta and NF-kappaB are required for human
      rhinovirus induced pro-inflammatory cytokine production in bronchial epithelial
      cells.
AB  - Rhinovirus infections cause the majority of acute exacerbations of airway
      diseases such as asthma and chronic obstructive pulmonary disease, with increased
      pro-inflammatory cytokine production by infected bronchial epithelial cells
      contributing to disease pathogenesis. Theses diseases are a huge cause of
      morbidity worldwide, and contribute a major economic burden to healthcare costs.
      Current steroid based treatments are only partially efficient at controlling
      virus induced inflammation, which remains an unmet therapeutic goal. Although NF
      kappaB has been implicated, the precise mechanisms of rhinovirus induction of pro
      inflammatory gene expression in bronchial epithelial cells are unclear. We
      hypothesised that rhinovirus replication and generation of dsRNA was an important
      process of pro-inflammatory cytokine induction. Using pharmalogical (2
      aminopurine and a new small molecule inhibitor) and genetic inhibition of the
      dsRNA binding kinase protein kinase R, striking inhibition of dsRNA (polyrIC) and
      rhinovirus induced CCL5, CXCL8 and IL-6 protein was observed. Using confocal
      microscopy, rhinovirus induced protein kinase R phosphorylation co-located with
      NF-kappaB p65 nuclear translocation. Focusing on CXCL8, both rhinovirus infection
      and dsRNA treatment required IkappaB kinase-beta for induction of CXCL8. Analysis
      of cis-acting sites in the CXCL8 promoter revealed that both rhinovirus infection
      and dsRNA treatment upregulated CXCL8 promoter activation via NF-kappaB and NF
      IL6 binding sites. Together, the results demonstrate the importance of dsRNA in
      induction of pro-inflammatory cytokines by rhinoviruses, and suggest that protein
      kinase R is involved in NF-kappaB mediated gene transcription of pro-inflammatory
      cytokines via IkappaB kinase-beta. These molecules regulating rhinovirus
      induction of inflammation represent therapeutic targets.

PMID- 16989900
TI  - Functional mapping and single chain construction of the anti-cytokeratin 8
      monoclonal antibody TS1.
AB  - The anti-cytokeratin (CK) 8 monoclonal antibody (mab) TS1 has been shown to
      efficiently bind to CK8 expressed in carcinomas in vivo. The anti-idiotypic
      antibody of TS1, alphaTS1, can be used to regulate the tumor:non-tumor ratio of
      TS1 by clearing non-tumor binding TS1 from the circulation. If the interaction of
      TS1 to CK8 and alphaTS1 is fully understood, mutations can be used to improve the
      tumor:non-tumor ratio. A scFv was made of the mab TS1 and residues earlier
      identified by Erlandsson et al. as important for the interaction with both its
      antigen CK8 and its anti-idiotype alphaTS1, were mutated to alanine or amides and
      expressed in E. coli. The effects of the mutations were studied by ELISA and
      residues important for the interactions to both CK8 and alphaTS1 were identified
      as mainly tyrosines, charged residues, a serine and a tryptophan. Altogether,
      nine amino acid residues in TS1 were found to be important in the interaction to
      alphaTS1 and six residues for the interaction to CK8. Important residues,
      clustered together in the modelled protein, were identified as residues from CDR
      3 of the heavy chain and the unexpected participation of a residue in CDR 2 of
      the light chain. Some of the important residues are likely to be hotspots.
      Hotspots constitute a few residues in an interaction that contribute most to the
      binding, energetically. Amino acid residues in hotspots often cluster together in
      the center of the interaction interface, but can also be spread out to the
      periphery. The hotspots are often surrounded by hydrophobic patches, which are
      seen in the modelled TS1 protein used in this study. Amino acid residues that
      increased the affinity when mutated were also identified for both interactions.
      These residues are likely to be located outside the interacting interface. It can
      from this study be concluded that it is wise to precede the mutational procedure
      with experiments that can give guidelines for the selection of which amino acid
      residues to mutate. If the guidelines from the chemical modifications from
      Erlandsson et al. not had been used, this study would have left some residues
      unmutated and thereby missed important information.

PMID- 16989901
TI  - Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy.
AB  - OBJECTIVE: To evaluate the effect of ruboxistaurin, an orally administered
      protein kinase C beta (PKC beta) isozyme-selective inhibitor, on vision loss in
      patients with diabetes. DESIGN: Thirty-six-month, randomized, double-masked,
      placebo-controlled, parallel, multicenter trial. PARTICIPANTS: Six hundred eighty
      five patients randomized at 70 clinical sites. METHODS: Ophthalmologic
      examination was performed at screening and at each 3-month visit. Retinopathy
      status was assessed every 6 months with Early Treatment Diabetic Retinopathy
      Study (ETDRS) standard 7-field 30 degrees color stereoscopic fundus photography.
      Levels of diabetic retinopathy and diabetic macular edema were determined by 2
      independent graders masked to site and treatment assignment, with additional
      independent adjudication as required. Eligible patients had a best-corrected
      visual acuity (VA) score of > or =45 letters, retinopathy level > or = 47A and <
      or = 53E, and no prior panretinal photocoagulation in at least one eye. MAIN
      OUTCOME MEASURE: Effect of oral ruboxistaurin (32 mg/day) on reduction of
      sustained moderate visual loss (> or =15-letter decrease in ETDRS VA score
      maintained > or = 6 months) in patients with moderately severe to very severe
      nonproliferative diabetic retinopathy. RESULTS: Sustained moderate visual loss
      occurred in 9.1% of placebo-treated patients versus 5.5% of ruboxistaurin-treated
      patients (40% risk reduction, P = 0.034). Mean VA was better in the ruboxistaurin
      treated patients after 12 months. Baseline-to-end point visual improvement of >
      or =15 letters was more frequent (4.9% vs. 2.4%) and > or =15-letter worsening
      was less frequent (6.7% vs. 9.9%) in ruboxistaurin-treated patients relative to
      placebo (P = 0.005). When clinically significant macular edema was >100 microm
      from the center of the macula at baseline, ruboxistaurin treatment was associated
      with less frequent progression of edema to within 100 microm (68% vs. 50%, P =
      0.003). Initial laser treatment for macular edema was 26% less frequent in eyes
      of ruboxistaurin-treated patients (P = 0.008). CONCLUSION: Oral ruboxistaurin
      treatment reduced vision loss, need for laser treatment, and macular edema
      progression, while increasing occurrence of visual improvement in patients with
      nonproliferative retinopathy.

PMID- 16989902
TI  - Implantable miniature telescope for the treatment of visual acuity loss resulting
      from end-stage age-related macular degeneration: 1-year results.
AB  - PURPOSE: To evaluate the safety and efficacy of an implantable visual prosthetic
      device (IMT; VisionCare Ophthalmic Technologies, Saratoga, CA) in patients with
      bilateral, end-stage age-related macular degeneration (AMD). DESIGN: Prospective,
      open-label, multicenter clinical trial with fellow eye controls. PARTICIPANTS: A
      total of 217 patients (mean age, 76 years) with AMD and moderate to profound
      bilateral central visual acuity loss (20/80-20/800) resulting from bilateral
      untreatable geographic atrophy, disciform scars, or both were enrolled. METHODS:
      A visual prosthetic device (implantable telescope), designed to enlarge retinal
      images of the central visual field, was implanted monocularly in the capsular bag
      after lens extraction. Fellow eyes were not implanted to provide peripheral
      vision and served as controls. Study patients participated in 6 visual
      rehabilitation visits after surgery. MAIN OUTCOME MEASURES: Best-corrected
      distance visual acuity (BCDVA) and best-corrected near visual acuity (BCNVA),
      quality-of-life scores from the National Eye Institute 25-item Visual Function
      Questionnaire (NEI VFQ-25) and the Activities of Daily Life scale, endothelial
      cell density (ECD), and incidence of complications and adverse events. RESULTS:
      At 1 year, 67% of implanted eyes achieved a 3-line or more improvement in BCDVA
      versus 13% of fellow eye controls (P<0.0001). Fifty-three percent of implanted
      eyes achieved a 3-line or more improvement in both BCDVA and BCNVA versus 10% of
      fellow eyes (P<0.0001). Mean BCDVA and BCNVA improved 3.5 lines and 3.2 lines,
      respectively, in implanted eyes versus 0.8 lines and 1.8 lines, respectively, in
      fellow eyes (P<0.0001). Change in visual acuity was not related to lesion type.
      Mean NEI VFQ-25 scores improved by more than 7 points from baseline (P<0.01) on 7
      of 8 relevant subscales. Eleven eyes did not receive the device because of an
      aborted procedure. Endothelial cell density was reduced by 20% at 3 months and
      25% at 1 year. The decrease in ECD was correlated with postsurgical edema
      (P<0.0001), and there was no evidence that endothelial cell loss is accelerated
      by ongoing endothelial trauma after implantation. CONCLUSIONS: This implantable
      visual prosthesis can improve visual acuity and quality of life in patients with
      moderate to profound visual impairment caused by bilateral, end-stage AMD.

PMID- 16989903
TI  - Effects of monomethyltin and dimethyltin compounds on heterologously expressed
      neuronal ion channels (Xenopus oocytes) and synaptic transmission (hippocampal
      slices).
AB  - The aim of this study was to investigate the effects of monomethyltin trichloride
      (MMT) and dimethyltin dichloride (DMT) on various neuronal ion channels
      heterologously expressed in Xenopus oocytes and on synaptic transmission in
      hippocampal slices of young (14-21 days old) and adult (2-4 months old) rats. The
      Xenopus oocyte expression system was chosen to allow direct assessment of the
      effects of MMT and DMT both on glutamate receptors sensitive to AMPA and NMDA and
      on various voltage-operated potassium and sodium channels. Hippocampal slices
      were used to analyze the effects of MMT and DMT on synaptic potentials generated
      by the important excitatory Schaffer collateral-CA1 synapse. In general, MMT and
      DMT were found to have no effect either on voltage-operated sodium and potassium
      channels or on the metabotropic glutamate receptor but they did differentially
      affect the functions of ionotropic glutamate receptors and glutamatergic synaptic
      transmission. MMT (100 microM) significantly reduced NMDA-mediated ion currents
      by up to 32%, but had no effect on ion currents through AMPA receptors. In slices
      of adult rats, MMT had no effect on the amplitudes of evoked fEPSPs and brought
      about a 35% reduction in the LTP amplitudes. In contrast, in slices of young rats
      MMT evoked a reversible 30% increase in the amplitudes of fEPSPs but had no
      effect on LTP induction. DMT (100 microM) reduced ion currents through NMDA
      receptor ion channels by up to 29% and those through AMPA-receptor ion channels
      by up to 7%. In hippocampal slices 100 microM DMT reduced the amplitudes of
      fEPSPs (adults: 50%; young rats: 70%) and LTP (adults: 40%; young rats: 55%).
      Neither of the organotins affected the paired-pulse facilitation at this synapse,
      indicating that the organotins exert their effects at the postsynaptic site. The
      action of MMT and DMT may contribute to the organotin-induced impairment of
      behavior patterns in connection with learning and memory.

PMID- 16989904
TI  - Emergence of community-associated methicillin resistant Staphylococcus aureus in
      Hawaii, 2001-2003.
AB  - OBJECTIVES: We conducted a retrospective study to determine trends and
      characteristics of community-associated methicillin-resistant Staphylococcus
      aureus (CA-MRSA) in Hawaii. METHODS: We reviewed medical records of patients with
      MRSA infections during July 2001-June 2003 in four healthcare facilities. A case
      was defined as a patient with MRSA infection (colonization excluded), diagnosed
      in ambulatory settings or < or = 48 h after hospitalization, without previous
      MRSA or healthcare risk factors. Pulsed-field gel electrophoresis (PFGE) and
      typing of resistance and toxin genes was performed in 40 MRSA isolates. RESULTS:
      CA-MRSA infections increased from 28 (23% of MRSA infections) to 65 (32%) per
      quarter over the 2-year period (P<0.05). Pacific islanders accounted for 51% of
      389 case-patients, but only 24% of the Hawaii population. In the pediatric
      hospital, Pacific Islanders represented 76% of 90 case-patients versus 35% of the
      hospital population. Hospital admission, required for 40% (154/389), was
      associated with prior antimicrobial treatment (P<0.01). The staphylococcal
      cassette chromosome mec type IV was detected in 38/40 isolates; 31 isolates
      carried Panton-Valentine leukocidin genes and 22 belonged to the same
      staphylococcal lineage. CONCLUSIONS: In Hawaii, prevention strategies for CA-MRSA
      infections should focus on Pacific Islanders. CA-MRSA infections in Hawaii appear
      to be related to strains causing disease throughout the United States.

PMID- 16989905
TI  - Lipoic acid as a novel treatment for Alzheimer's disease and related dementias.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that
      destroys patient memory and cognition, communication ability with the social
      environment and the ability to carry out daily activities. Despite extensive
      research into the pathogenesis of AD, a neuroprotective treatment - particularly
      for the early stages of disease - remains unavailable for clinical use. In this
      review, we advance the suggestion that lipoic acid (LA) may fulfil this
      therapeutic need. A naturally occurring precursor of an essential cofactor for
      mitochondrial enzymes, including pyruvate dehydrogenase (PDH) and alpha
      ketoglutarate dehydrogenase (KGDH), LA has been shown to have a variety of
      properties which can interfere with pathogenic principles of AD. For example, LA
      increases acetylcholine (ACh) production by activation of choline
      acetyltransferase and increases glucose uptake, thus supplying more acetyl-CoA
      for the production of ACh. LA chelates redox-active transition metals, thus
      inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen
      species (ROS), thereby increasing the levels of reduced glutathione. Via the same
      mechanisms, downregulation redox-sensitive inflammatory processes is also
      achieved. Furthermore, LA can scavenge lipid peroxidation products such as
      hydroxynonenal and acrolein. The reduced form of LA, dihydrolipoic acid (DHLA),
      is the active compound responsible for most of these beneficial effects. R-alpha
      LA can be applied instead of DHLA, as it is reduced by mitochondrial lipoamide
      dehydrogenase, a part of the PDH complex. In this review, the properties of LA
      are explored with particular emphasis on how this agent, particularly the R-alpha
      enantiomer, may be effective to treat AD and related dementias.

PMID- 16989906
TI  - Regional cerebral glucose metabolism in patients with secondary depressive
      episodes after fatal pancreatic cancer diagnosis.
AB  - BACKGROUND: Secondary depression is common in the clinical oncology setting after
      pancreatic cancer diagnosis, following which the patients have to face the fact
      that they have a cancer with an extremely poor prognosis. However, the specific
      pathophysiology remains unclear. The present study examined the regional cerebral
      glucose metabolism using F18-fluorodeoxyglucose (F18-FDG) positron emission
      tomography (PET) in antidepressant-naive pancreatic cancer patients with a
      depressive episode after their cancer diagnosis and before their cancer
      treatment. METHODS: Regional cerebral glucose metabolism in pancreatic cancer
      patients without any antidepressant medication after the cancer diagnosis was
      measured with F18-FDG PET. A depressive episode after the cancer diagnosis was
      defined as including major and minor depressive episodes, and was diagnosed using
      the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV). The prefrontal
      and limbic regions were the primary regions-of-interest, and an uncorrected value
      of p<0.005 was used as significant. RESULTS: Six of 21 pancreatic cancer patients
      were diagnosed as having a depressive episode. Significantly higher glucose
      metabolism in depressed patients was found in the subgenual anterior cingulate
      cortex (sACC) (uncorrected p=0.002). LIMITATIONS: There was a small number of
      subjects, and there were no healthy controls. CONCLUSIONS: The higher metabolism
      in the sACC may be associated with the pathophysiology of secondary depressive
      episodes in patients following pancreatic cancer diagnosis.

PMID- 16989907
TI  - Pharmacological treatment of acute mania in psychiatric in-patients between 1994
      and 2004.
AB  - BACKGROUND: In a cross-section approach we investigated prescription practice in
      acute mania in 63 German, Swiss and Austrian hospitals between 1994 and 2004.
      METHODS: Our data were gathered from a large drug safety program (AMSP) within
      which on two reference days each year all administered drugs are recorded. For
      the present study, all cases with a primary diagnosis of acute euphoric mania
      (n=1291) or mixed-state mania (n=143) were identified. Prescription rates from
      two periods, 1994 to 1999 and 2000 to 2004, were compared. RESULTS: In euphoric
      mania, prescription of lithium decreased by about one-fifth (43.3% to 34.5%,
      p<0.01), while prescription of anticonvulsants increased by one-half (from 40.0%
      to 60.7%, p<0.001). Administration of atypical antipsychotics more than doubled
      (18.5% to 43.9%, p<0.001), while use of typical antipsychotics decreased
      significantly (56.9% to 27.8%, p<0.001). Overall prescription rates of
      antipsychotics (79.6% vs. 81.6%) and antidepressants (14.0% vs. 15.5%) remained
      stable, while administration of tranquilizers increased significantly (26.3% to
      34.3%, p<0.01). In mixed-state mania, similar trends over time to those seen in
      euphoric mania were observed for lithium (43.2% to 33.3%), anticonvulsants (50.0%
      to 69.7%, p<0.05) and tranquilizers (22.7% to 40.4%). Prescription rates of
      antipsychotics slightly increased (63.6% to 72.7%), while prescription of
      antidepressants slightly decreased (54.5% to 46.5%). Polypharmacy was a common
      phenomenon: patients with euphoric mania were treated with a mean number of 2.9+/
      1.2 psychotropic agents, and patients with mixed-state mania with 3.3+/-1.5
      psychotropic agents. Both groups showed a significant increase over time. Second
      generation atypical antipsychotics were adopted quite rapidly for the treatment
      of acute mania considering the availability of the scientific evidence at that
      time. Off-label use was a common phenomenon. Deviations from recommended
      guidelines were found mainly in the use of antidepressant and antipsychotic drugs
      both in mixed-state and euphoric mania. CONCLUSIONS: Naturalistic prescription
      studies like this may encourage a critical scrutiny of clinical treatment habits
      and may also drive further research thus moderating potential differences between
      evidence-based knowledge and everyday clinical practice.

PMID- 16989908
TI  - Jugular foramen fibromatosis in a 3-month-old male.
AB  - A 3-month-old male with a chief complaint of episodic choking with feeds and a
      hoarse cry is presented. Left eye ptosis and asymmetric soft palate elevation
      were detected on physical examination. Fiberoptic examination showed a left vocal
      fold paresis and pooling of secretions in the pyriform sinuses. MRI demonstrated
      an ill-defined lesion at the left jugular foramen extending into the left carotid
      sheath. A fine needle biopsy revealed spindle shaped cells consistent with
      fibromatosis. The histopathology of fibromatosis and the differential diagnosis
      of jugular foramen masses in children will be described. To our knowledge, this
      represents the earliest reported case of fibromatosis in the jugular foramen.

PMID- 16989909
TI  - Development of chronic tests for endocrine active chemicals. Part 2: an extended
      fish early-life stage test with an androgenic chemical in the fathead minnow
      (Pimephales promelas).
AB  - The Endocrine Modulators Study Group (EMSG) of the European Chemical Industry has
      proposed an extended fish early-life stage (ELS) test based on OECD test
      guideline 210 in combination with a fish pair-breeding reproduction study as a
      possible alternative for fish full life cycle testing. In this paper the androgen
      methyldihydrotestosterone (MDHT) was tested in an extended ELS test with fathead
      minnow supplementary to such a test with the weak estrogen 4-tert-pentylphenol
      (4TPP). Main endpoints were secondary sexual characteristics (SSC), plasma
      vitellogenin (VTG) induction and gonadal development. Early blastula embryos were
      exposed to 0, 0.10, 0.32 and 1.0 microgMDHTl(-1) for up to 114 days post-hatch
      (dph). A batch of fish exposed to 1.0 microg l(-1) was transferred to clean water
      after 30 or 63 dph for the remainder of the study. Ethinylestradiol (EE2) was
      included as estrogenic reference substance at 0.01 microg l(-1). Exposure to MDHT
      had no significant effect on hatching success or survival, but significantly
      increased the condition factor of fish exposed for 63 and 114 dph (up to 150% of
      the control). At 63 dph MDHT exposure induced appearance of tubercles on the
      snout (a male SSC) of more than 80% of fish. Compared to the controls, plasma VTG
      was not detectable or significantly lower in fish exposed to MDHT at 0.10
      microg/l, but not significantly affected at higher MDHT concentrations. Both
      lower levels of MDHT significantly inhibited the development of female gonads as
      of 30 dph. Fish exposed to MDHT at 0.32 and 1.0 microg l(-1) showed higher
      incidences of mixed sex gonads (10-25%) and smaller testes or dysplasia of
      gonadal tissue. Dysplasia was present in 80% of the fish continuously exposed to
      1.0 microg l(-1) up to 114 dph, but reversible when fish were transferred to
      dilution water. Results indicate that suppression of ovarian development was the
      most sensitive endpoint for MDHT exposure after 30 dph. Other endpoints (e.g.,
      growth and SSC) required exposure during at least up to 63 dph to yield a
      significant effect. Androgenic effects on VTG production required even longer
      exposure, i.e., until sufficient number of females had matured.

PMID- 16989910
TI  - Growth factor-dependent actions of PACAP on oligodendrocyte progenitor
      proliferation.
AB  - We previously reported that rat oligodendrocyte progenitors (OLP) express
      receptors for the pituitary adenylyl cyclase-activating peptide (PACAP) in vivo
      and in vitro. Addition of PACAP to cultured OLP triggered a potent elevation in
      intracellular cAMP contents, a dose-dependent stimulation of proliferation, and a
      delay in myelinogenesis (Lee M, Lelievre V, Zhao P, Torres M, Rodriguez W, Byun
      JY, Doshi S, Ioffe Y, Gupta G, de los Monteros AE, de Vellis J, Waschek J.
      Pituitary adenylyl cyclase-activating polypeptide stimulates DNA synthesis but
      delays maturation of oligodendrocyte progenitors. J Neurosci. 2001 21:3849-59.).
      In an attempt to understand how PACAP might interact with growth factors known to
      stimulate OLP proliferation, we investigated PACAP actions on OLP proliferation
      in the presence of Fibroblast Growth Factor-2 (FGF-2) and PDGF. Multiple PACAP
      receptor subtype mRNAs and splice variants were detected in these cultures. PACAP
      by itself potently stimulated OLP proliferation and enhanced the ability of FGF-2
      to stimulate DNA synthesis. In contrast, this peptide strongly antagonized the
      mitogenic effects of PDGF in association with a reduction of PDGFalpha receptor
      gene expression. Additionally, we investigated the interaction of PACAP with the
      morphogenetic factor sonic hedgehog (Shh), which recently was shown to be crucial
      for oligodendrocyte generation. OLP cultures were found to express mRNAs for both
      ptc1 (Shh receptor) and gli1 (Shh target gene) and responded to Shh treatment
      with an increase in proliferation. PACAP antagonized the ability of Shh to
      stimulate OLP proliferation. Moreover, transcriptional targets of Shh signaling
      were also reduced by this treatment, suggesting that PACAP directly antagonized
      Shh signaling. These studies reveal complex in vitro interactions of PACAP with
      other factors involved in OLP development.

PMID- 16989911
TI  - The VIP-receptor system in neuroblastoma cells.
AB  - Neuroblastoma (NB), the most common extracranial tumor during childhood arises
      from the embryonic sympathetic nervous system. Remarkably, NB can spontaneously
      regress, even after metastasis, leading to complete remission. Subpopulations of
      neuroblastic (N-type) and nonneuronal cells coexist in NB. Expression of the high
      affinity nerve growth factor (NGF) TrkA receptor in NB is correlated with good
      prognosis, while MYCN amplification is associated with advanced stages of
      disease. N-type cells undergo differentiation when treated with different
      compounds, such as retinoids, phorbol esters, growth and neurotrophic NGF and
      neuropeptides, especially vasoactive intestinal peptide (VIP). These substances
      stabilize proliferation, leading to a more mature neuronal phenotype, neurite
      outgrowth and induction of expression of sympathetic neuronal markers. Therefore,
      receptors for these substances and their associated signalling pathways, appear
      like promising targets for the development of novel NB therapeutics. The aim of
      the present review is to summarize the quite considerable array of data,
      concerning production of VIP and related peptides, expression of their receptors
      in NB and the key regulation exerted by the VIP-receptor system in the control of
      NB cell behaviour.

PMID- 16989912
TI  - Dose-dependent Venlafaxine-induced sinus tachycardia.

PMID- 16989913
TI  - Radiation dose and long term risk of cardiac pathology following radiotherapy and
      anthracyclin for a childhood cancer.
AB  - PURPOSE: To determine the cardiac status in children 15 years (yrs) or more after
      a solid tumour treatment. PATIENTS AND METHODS: Of the 447 patients, 229 were
      fully studied and 218 were not. The following cardiac evaluation was proposed to
      all the 447 consecutive patients: (1) cardiac Doppler US by one of two expert
      cardiologists; (2) cardiac rhythm and conduction abnormalities including 24-h
      holter ECG; (3) (131)I-mIBG myocardial scintigraphy; (4) serum brain natriuretic
      peptide levels at rest; (5) an exercise test with VO(2)max measurement. The
      radiation dose delivered to 7 points in the heart was estimated for all patients
      who had received radiotherapy. RESULTS: Cardiac disorder was diagnosed in 89
      evaluated patients (39%) including 24 heart failures and 65 other asymptomatic
      cardiac diseases. When adjusting on potential confounders, cardiac disorder and
      cardiac failure risks were respectively linear (ERR at 1 Gy: 26%) and linear
      quadratic (ERR at 1 Gy: 19%) functions of the average radiation dose received to
      the heart. No interaction between cumulative dose of adriamycin and average
      radiation dose was evidenced for cardiac disorders, but the ERR/Gy of cardiac
      failure was higher for patients receiving less than 350 mg/m(2) of Adriamycin.
      CONCLUSION: Long term heart pathologies are probably one of the major iatrogenic
      risks encored by patients who survived a childhood cancer. This study strongly
      emphasizes the need to limit the heart irradiation during radiotherapy,
      particularly, for patients who also received or were susceptible to later
      received adriamycin.

PMID- 16989914
TI  - Respiratory sinus arrhythmia as a function of state anxiety in healthy
      individuals.
AB  - Respiratory sinus arrhythmia (RSA) was examined in relation to state and trait
      anxiety in healthy individuals. Time-frequency analyses of HR-power spectrum in
      the high frequency region (0.12-0.40 Hz), related to RSA, were examined in 43
      women and 39 men. Based on median split, the participants were divided into high
      and low state and trait anxiety groups. The main result showed that high state
      anxious individuals had higher RSA-magnitude (HF-power) than low state anxious
      individuals. The higher RSA-magnitude in the former group was interpreted as
      reflecting increased attention or vigilance together with motor and behavioural
      inhibition. No significant effects of trait anxiety or gender were found.

PMID- 16989915
TI  - Beneficial effects of FK506 for experimental temporal lobe epilepsy.
AB  - FK506, originally classified as an immunosuppressant, may also be implicated in
      some events in the central nervous system. FK506 elicits both neuroprotective and
      neurotrophic effects in vitro. FK506 is neuroprotective for focal cerebral
      ischemia, but it is not clear whether FK506 has neuroprotective effects for other
      brain diseases. In this study, we investigated possible neuroprotective effects
      of FK506 in experimental temporal lobe epilepsy (TLE) induced by kainic acid (KA)
      or trimethyltin (TMT). In rat models, we observed marked protection against
      seizures, abnormal behaviors, and accompanying delayed neuronal damage in the
      hippocampus by the systemic injection of FK506.

PMID- 16989916
TI  - Carcinoembryonic antigen (CEA) mimicry by an anti-idiotypic scFv isolated from
      anti-Id 6.C4 hybridoma.
AB  - Since carcinoembryonic antigen (CEA) is expressed during embryonic life, it is
      not immunogenic in humans. The use of anti-idiotypic (Id) antibodies as a
      surrogate of antigen in the immunization has been considered a promising strategy
      for breaking tolerance to some tumor associated antigens. We have described an
      anti-Id monoclonal antibody (MAb), designated 6.C4, which is able to mimic CEA
      functionally. The anti-Id MAb 6.C4 was shown to elicit antibodies that recognized
      CEA in vitro and in vivo. In the present study, we sought to verify whether a
      single chain (scFv) antibody obtained, the scFv 6.C4, would retain the ability to
      mimic CEA. Two scFv containing the variable heavy and light chain domains of 6.C4
      were constructed with a 15-amino acid linker: one with and another without signal
      peptide. DNA immunization of mice with both forms of scFv individually elicited
      antibodies able to recognize CEA.

PMID- 16989917
TI  - Characterization of an early gene encoding for dUTPase in Rana grylio virus.
AB  - dUTPase (DUT) is a ubiquitous and important enzyme responsible for regulating
      levels of dUTP. Here, an iridovirus DUT was identified and characterized from
      Rana grylio virus (RGV) which is a pathogen agent in pig frog. The DUT encodes a
      protein of 164aa with a predicted molecular mass of 17.4 kDa, and its
      transcriptional initiation site was determined by 5'RACE to start from the
      nucleotide A at 15 nt upstream of the initiation codon ATG. Sequence comparisons
      and multiple alignments suggested that RGV DUT was quite similar to other
      identified DUTs that function as homotrimers. Phylogenetic analysis implied that
      DUT horizontal transfers might have occurred between the vertebrate hosts and
      iridoviruses. Furthermore, its temporal expression pattern during RGV infection
      course was characterized by RT-PCR and Western blot analysis. It begins to
      transcribe and translate as early as 4h postinfection (p.i.), and remains
      detectable at 48 h p.i. DUT-EGFP fusion protein was observed in the cytoplasm of
      pEGFP-N3-Dut transfected EPC cells. Immunofluorescence also confirmed DUT
      cytoplasm localization in RGV-infected cells. Using drug inhibition analysis by a
      de novo protein synthesis inhibitor (cycloheximide) and a viral DNA replication
      inhibitor (cytosine arabinofuranoside), RGV DUT was classified as an early (E)
      viral gene during the in vitro infection. Moreover, RGV DUT overexpression was
      shown that there was no effect on RGV replication by viral replication kinetics
      assay.

PMID- 16989918
TI  - Characterization of herpes simplex virus type 1 recombinants that express and
      incorporate high levels of HCV E2-gC chimeric proteins.
AB  - We report the construction of two HSV-1 recombinants encoding chimeric forms of
      the E2 glycoprotein of HCV-1a composed of the ectodomain of E2 (aa384-611 or 384
      711) fused to different parts of the transmembrane and cytoplasmic domain of the
      HSV-1 gC glycoprotein (gC). The parental HSV-1, known as KgBpK(-)gC(-), is
      deleted for gC and the main heparan sulphate (HS) binding domain of gB, and it
      exhibits impaired binding (ca. 80%) to HS compared to the wild type virus KOS
      [Laquerre, S., Argnani, R., Anderson, D.B., Zucchini, S., Manservigi, R.,
      Glorioso, J.C., 1998. Heparan sulphate proteoglycan binding by herpes simplex
      virus type 1 glycoproteins B and C, which differ in their contributions to virus
      attachment, penetration, and cell-to-cell spread. J. Virol. 72, 6119-6130]. We
      show that gC:E2 proteins are efficiently expressed and transported to the cell
      surface. We also demonstrate that HSV-1 can incorporate both gC:E2 chimeric
      proteins into particles and show that incorporation of both chimeric molecules in
      the viral envelope partially restored binding (ca. 20%) of the HSV-1 recombinants
      to heparan sulphate. Finally, we showed that the gC:E2ScaI chimeric glycoprotein
      was able to bind a recombinant form of hCD81 and virion-expressed gC:E2ScaI
      permitted the binding of the HSV-1 recombinant virus to the hCD81 molecule.

PMID- 16989919
TI  - In vitro and in vivo gene-transferring characteristics of novel cationic lipids,
      DMKD (O,O'-dimyristyl-N-lysyl aspartate) and DMKE (O,O'-dimyristyl-N-lysyl
      glutamate).
AB  - We chemically synthesized two different cationic lipids consisting of a core of
      lysine, two C-14 hydrocarbon chains, and either aspartatic acid or glutamic acid.
      The lipids were assigned the acronyms, DMKD and DMKE. Cationic liposomes prepared
      with the two different lipids were tested for their gene-transferring
      capabilities in various cell lines compared with that of control DOTAP liposomes.
      Under the same experimental conditions, the order of in vitro gene transfection
      efficiency was DMKE>or=DMKD>DOTAP. To identify the parameters influencing
      transfection efficiency, the DNA-binding affinities of the liposomes were
      compared and changes in particle size and surface charge were examined after
      complex formation. Both the DNA-binding affinity of the liposomes and the cell
      surface-binding affinity of the liposome-pDNA complexes were crucial for gene
      transfection. In addition, intravenously administered DMKE and DMKD liposomes
      exhibited different biodistribution characteristics and intensity of in vivo
      organ transfection from the DOTAP liposomes. Compared to the DOTAP liposomes,
      they were more readily transferred to the liver. Interestingly, when they were
      directly injected into tumor tissues, the DMKE lipoplexes were able to induce
      more efficient transgene expression in these tissues than the DOTAP and DMKD
      lipoplexes. This study suggests that a small difference in the cationic lipid
      backbone structure significantly affects gene-transferring capabilities. DMKE and
      DMKD liposomes can be utilized as efficient gene-transferring vehicles for
      hepatic or intra-tumoral gene transfection.

PMID- 16989920
TI  - Improved nasal absorption of salmon calcitonin by powdery formulation with N
      acetyl-L-cysteine as a mucolytic agent.
AB  - To establish a new formulation technology for the nasal delivery of peptide and
      protein drugs, we examined whether a mucolytic agent, N-acetyl-L-cysteine (NAC),
      could enhance the nasal absorption of a powder form of salmon calcitonin, a model
      peptide drug. We used ethylcellulose as an inert water-insoluble excipient.
      Various test formulations were prepared, and the effects on nasal absorbability
      were evaluated in rats and dogs. The powder formulation with NAC gave significant
      nasal absorption of SCT in both animal models, with absolute bioavailabilities of
      30.0% in rats and 24.9% in dogs. Also, nasal administration of this formulation
      gave a quicker absorption rate than subcutaneous administration of SCT. NAC may
      reduce nasal fluid viscocity and improve accessibility of the drug to the
      epithelial membrane. The powder SCT/NAC/ethylcellulose formulation did not induce
      irritation or histological damage to the nasal membrane in rabbits. These results
      suggest that this formulation technology may be widely applicable for the nasal
      delivery of peptide or protein drugs.

PMID- 16989921
TI  - Post-hospital care of stroke patients in Taipei: use of services and policy
      implications.
AB  - BACKGROUND AND PURPOSE: Population ageing in Taiwan is proceeding at an
      accelerating rate. The percentage of elderly is expected to increase from 9.7% in
      2005 to 20% in 2025. As the population ages, more people will suffer from chronic
      conditions and will need more post-hospital care. Health policies need to adapt
      itself to meet the changing needs of society. The purposes of this study were to
      describe the use of post-hospital care among stroke patients in Taipei and to
      discuss policy implications. METHODS: This research used a longitudinal
      prospective study design, recruiting stroke patients from seven hospitals in the
      Taipei area. Patients were followed-up for 6 months after discharge with surveys
      at 1, 3, and 6 months. Information on their needs and uses of post-hospital care
      was collected. RESULTS: About 9% of patients were institutionalized at 1 month,
      and the percentage did not vary much throughout the 6 months of the study. Little
      movement occurred between institutions and homes within 6 months after discharge.
      Most patients relied on family members to provide assistance with activities of
      daily living. Little utilization of formal services occurred. The use of foreign
      care attendants was common, and it increased with time. Few unmet needs were
      observed for nursing care, while significant unmet needs were observed for
      rehabilitative services. DISCUSSIONS: Taiwan is not prepared to adequately meet
      the care demands of an ageing society. Continuing to support family members with
      additional home- or community-based services resources should be a policy
      priority. More efforts should be placed on educating family caregivers about the
      availability and benefits of community-based services during discharge planning.
      The use of foreign care attendants has become a mainstream practice. Regulations
      to protect the rights of foreign care attendants and to improve their quality of
      care need to be established.

PMID- 16989922
TI  - Nodule management protocol of the NELSON randomised lung cancer screening trial.
AB  - In December 2003, the Dutch-Belgian NELSON trial, a Dutch acronym for "Nederlands
      Leuvens Longkanker Screenings ONderzoek", has been launched. Primary objective of
      the NELSON trial is to investigate whether screening for lung cancer by 16
      detector multi-slice CT with 16 mm x 0.75 mm collimation and 15 mm table feed per
      rotation (pitch=1.5) in year 1, 2 and 4 will lead to a decrease in lung cancer
      mortality in high risk subjects of at least 25% compared to a control group which
      receives no screening. In this paper, the screening regimen and the
      classification and management of the screen-detected nodules at baseline and
      incidence screening is presented. This is the first large lung cancer screening
      trial in which the nodule management protocol is based on volumetric nodule
      assessment and the presence or absence of growth. Furthermore, the quality
      assurance measures and the NELSON management system (NMS) are presented.

PMID- 16989923
TI  - Systemic lupus erythematosus and the brain: what mice are telling us.
AB  - Neuropsychiatric symptoms occur in systemic lupus erythematosus (SLE), a complex,
      autoimmune disease of unknown origin. Although several pathogenic mechanisms have
      been suggested to play a significant role in the etiology of the disease, the
      exact underlying mechanisms still remain elusive. Several inbred strains of mice
      are used as models to study SLE, which exhibit a diversity of central nervous
      system (CNS) manifestations similar to that observed in patients. This review
      will attempt to give a brief overview of the CNS alterations observed in these
      models, including biochemical, structural and behavioral changes.

PMID- 16989924
TI  - Gene transfer into Purkinje cells using herpesviral amplicon vectors in
      cerebellar cultures.
AB  - Purkinje cells play a crucial role in sensory motor coordination since they are
      the only output projection neurons in the cerebellar cortex and are affected in
      most spinocerebellar ataxias. They stand out in the central nervous system due to
      their large size and their profusely branched dendritic arbor. However, molecular
      and cellular studies on Purkinje cells are often hampered by the difficulty of
      maintaining these cells in culture. Here we report an easy, robust and
      reproducible method to obtain Purkinje-enriched mixed cerebellar cell cultures
      from day 16 mouse embryos using papain digestion and a semi-defined culture
      medium, being the composition of the culture approximately 20% Purkinje cells,
      70% non-Purkinje neurons and 10% glial cells. We demonstrate that efficient gene
      transfer into Purkinje cells (as well as into other cerebellar populations) is
      possible using herpes simplex virus-1 (HSV-1)-derived vectors. Indeed, up to 50%
      of the Purkinje cells can be transduced and gene expression may persist for at
      least 14 days. As a result, this procedure permits functional gene expression
      studies to be carried out on cultured Purkinje neurons. To demonstrate this, we
      show that the expression of a dominant-negative form of glycogen synthase kinase
      3 protects Purkinje neurons against cell death triggered by a chemical inhibitor
      of phosphatidylinositol-3 kinase. In summary, we have established reproducible
      and reliable cerebellar cell cultures enriched for Purkinje cells which enables
      gene transfer studies to be carried out using herpesviral vectors.

PMID- 16989925
TI  - Developing collaborative practice in health and social care education.
      Proceedings of the First Nurse Education International Conference. May 14-16,
      2006. Vancouver, Canada.

PMID- 16989926
TI  - Development of a commercial cigarette "market map" comparison methodology for
      evaluating new or non-conventional cigarettes.
AB  - A "market map" comparison methodology for cigarette smoke chemistry yields is
      presented. Federal Trade Commission machine-method smoke chemistry was determined
      for a range of filtered cigarettes from the US marketplace. These data were used
      to develop illustrative market maps for each smoke constituent as analytical
      tools for comparing new or non-conventional cigarettes to a sampling of the
      broader range of marketplace cigarettes. Each market map contained best-estimate
      "market-means," showing the relationship between commercial cigarette constituent
      and tar yields, and yield "market ranges" defined by prediction intervals. These
      market map means and ranges are the basis for comparing new cigarette smoke
      yields to those of conventional cigarettes. The potential utility of market maps
      for evaluating differences in smoke chemistry was demonstrated with 1R4F and 2R4F
      Kentucky reference cigarettes, an Accord cigarette, and an Advance cigarette.
      Conventional cigarette tobacco nicotine, nitrate, soluble ammonia, and tobacco
      specific nitrosamine levels are reported. Differences among conventional
      cigarette constituent yields at similar tar levels were explained in part by the
      chemical composition range of those cigarette tobaccos. The study also included a
      comparison of smoke constituent yields and in vitro smoke cytotoxicity and
      mutagenicity assay results for the 1R4F Kentucky reference cigarette and its
      replacement 2R4F. Significant smoke yield differences were noted for lead, NNK,
      and NNN. The majority of their smoke constituent yields were within the market
      range developed from the sampled conventional cigarettes. Within the sensitivity
      and specificity of the in vitro bioassays used, smoke toxic activity differences
      for the two reference cigarettes were not statistically significant. These
      results add to the limited information available for the 2R4F reference
      cigarette.

PMID- 16989927
TI  - Benzene exposure in the shoemaking industry in China, a literature survey, 1978
      2004.
AB  - This article presents a summary of benzene exposure levels in the shoemaking
      industry in China reported in the Chinese medical literature between 1978 and
      2004. A comprehensive search identified 182 papers reporting such exposure data.
      These papers could be classified into two categories: benzene poisoning case
      reports and industrial hygiene surveys. From each paper, the following
      information was abstracted whenever available: location and year of occurrence,
      occupation and/or task involved, benzene content in adhesives/solvents, work
      environment, working conditions, working hours, diagnosis, and air monitoring
      data of benzene. A total of 333 benzene measurements (88 averages, 116 minimums,
      129 maximums) in the shoemaking industry were reported in the 182 papers
      identified. The data were analyzed in terms of geographical location, time
      period, type of ownership (state, township, or foreign), type of report (benzene
      poisoning reports vs. industrial hygiene surveys), and job title (work activity)
      or process. The reported data covered a wide range; some measurements were in
      excess of 4500 mg/m(3). Thirty-five percent of the reported benzene
      concentrations were below 40 mg/m(3), which was the national occupational
      exposure limit (OEL) for benzene between 1979 and 2001. The remaining 65%
      measurements, which exceeded the national OEL in effect at the time, and were
      distributed as follows: 40-100 mg/m(3), 11%; 100-300 mg/m(3), 21%; 300-500
      mg/m(3), 13%; and 500+ mg/m(3), 20%. However, only 24% of the reported
      measurements after 2002 were below 6 mg/m(3), i.e., Permissible Concentration
      Time Weighted Average (PC-TWA) and 10 mg/m(3), i.e., Permissible Concentration
      Short Term Exposure Limit (PC-STEL), the newly amended benzene OELs in effect
      after May 2002. The data demonstrated that the majority of the facilities in the
      shoemaking industry reported in the literature were not in compliance of the OEL
      for benzene in effect at the time. Overall, the data show a clear downward trend
      of benzene exposure levels over the years, particularly after the introduction of
      the new lower OEL in 2002. Even though substantially lower when compared to
      levels in the past, current benzene exposure measurements from the literature
      review suggest that many facilities in the shoemaking industry in China have
      benzene concentrations that are still above the new OEL. The reported data,
      stratified by job, year and survey reason, can be used as part of the information
      and analysis for developing a job-exposure matrix in retrospective exposure
      assessment and thus may be part of the information used in developing historical
      exposure estimates in epidemiologic studies of shoe workers.

PMID- 16989928
TI  - The sexuality and social performance of androgen-deprived (castrated) men
      throughout history: implications for modern day cancer patients.
AB  - Androgen-deprivation therapy (ADT) via either surgical or chemical castration is
      the standard treatment for advanced prostate cancer (PCa). In North America, it
      is estimated that more than 40,000 men start ADT each year. The side effects of
      this treatment are extensive and include gynecomastia, erectile dysfunction, and
      reduced libido. These changes strongly challenge patients' self-identity and
      sexuality. The historical term for a man who has been castrated is 'eunuch', now
      a pejorative term implying overall social and sexual impotence. In this paper, we
      review key historical features of eunuch social performance and sexuality from a
      variety of cultures in order to assess the validity of contemporary stereotypes
      of the androgen-deprived male. Data were taken from secondary sources on the
      history of Byzantium, Roman Antiquity, Early Islamic societies, the Ottoman
      Empire, Chinese Dynasties, and the Italian Castrati period. This cross-cultural
      survey shows that castrated men consistently held powerful social positions that
      yielded great political influence. Many eunuchs were recognized for their
      loyalty, managerial style, wisdom, and pedagogical skills. Furthermore, rather
      than being consistently asexual and celibate, they were often sexually active. In
      certain cultures, they were objects of sexual desire for males, or females, or
      both. Collectively, the historical accounts suggest that, given the right
      cultural setting and individual motivation, androgen deprivation may actually
      enhance rather than hinder both social and sexual performance. We conclude that
      eunuch history contradicts the presumption that androgen deprivation necessarily
      leads to social and sexual impotence. The capabilities and accomplishments of
      eunuchs in the past gives patients on ADT grounds for viewing themselves in a
      positive light, where they are neither socially impotent nor sexually chaste.

PMID- 16989929
TI  - Basilar artery blood flow velocity changes in patients with panic disorder
      following 35% carbon dioxide challenge.
AB  - PURPOSE: We compared the mean basilar artery blood flow velocity (BABFV) between
      patients with panic disorder and healthy subjects both at rest and immediately
      following carbon dioxide (CO(2)) challenge, and examined the effects of treatment
      on BABFV. METHODS: Twenty four patients with panic disorder with or without
      agoraphobia and 12 healthy comparison subjects were studied. Visual Analog
      Anxiety Scale was used to evaluate the anxiogenic effect of 35% CO(2) inhalation.
      Mean BABFV was monitored using transcranial Doppler ultrasonography at rest and
      10, 20, 30, 60, 90, 120 s after 35% CO(2) challenge both before and after four
      weeks treatment with paroxetine. RESULTS: The hemodynamic response pattern of
      basilar artery to CO(2) inhalation was significantly different between two
      groups. CO(2) rapidly triggered blood flow velocity in basilar artery amongst
      panic patients but not in healthy comparisons. The mean time to normalization of
      BABFV was significantly longer in panic patients. Four weeks of treatment with
      paroxetine led to a significantly reduced mean BABFV after 35% CO(2) inhalation
      in comparison with pretreatment. CONCLUSIONS: Patients with panic disorder had
      impaired cerebral regulatory mechanisms observed as a change in response
      characteristics in BABFV in response to CO(2) inhalation. Treatment with
      paroxetine reduced the increase of BABFV seen in patients after the CO(2)
      challenge.

PMID- 16989930
TI  - Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida
      albicans for inhibition by different antifungal azoles.
AB  - Inhibition of fungal lanosterol-14 alpha-demethylase (CYP51) is the working
      principle of the antifungal activity of azoles used in agriculture and medicine.
      Inhibition of human CYP51 may result in endocrine disruption since follicular
      fluid-meiosis activating steroid (FF-MAS), the direct product of lanosterol
      demethylation, is involved in the control of meiosis. To investigate the
      specificity of antifungal agents for the fungal enzyme, assays to determine
      inhibitory potencies of 13 agricultural fungicides and 6 antimycotic drugs were
      established. FF-MAS product formation was measured by LC-MS/MS analysis in the
      incubations using lanosterol as substrate. Recombinant human enzyme (hCYP51) was
      available from BD Gentest. CYP51 of Candida albicans (cCYP51) was co-expressed
      with Candida tropicalis oxidoreductase in the baculovirus system. IC(50) values
      of 13 fungicides for cCYP51 ranged about six-fold (0.059-0.35 microM); for hCYP51
      the range was about 30-fold (1.3-37.2 microM). The most favourable IC(50) ratio
      human to Candida was observed for imazalil (440-fold), while the specificity of
      epoxiconazole and tebuconazole for cCYP51 was only by a factor of 10. For the
      antimycotic drugs, the range of IC(50) values for cCYP51 was similar to those of
      fungicides (0.039-0.30 microM). For the inhibition of hCYP51, IC(50) values split
      into two classes: the newer drugs fluconazole and itraconazole showed little
      inhibition (> or = 30 microM) while the older drugs were even more potent than
      the agricultural fungicides, with miconazole being the most potent (0.057
      microM). No correlation was seen between the IC(50) values determined for the two
      enzymes, indicating that a housekeeping gene can show significant diversity if
      inhibition is concerned. Our data indicate that fungicide residues in food are
      unlikely to exert a relevant inhibition of CYP51 in humans whereas systemic use
      of some antimycotic drugs, e.g. ketoconazole or miconazole, should be carefully
      considered regarding disturbance of human steroid biosynthesis.

PMID- 16989932
TI  - A new role of diacylglycerol kinase alpha on the secretion of lethal exosomes
      bearing Fas ligand during activation-induced cell death of T lymphocytes.
AB  - Exosomes are small membrane vesicles that intracellularly accumulate into late or
      multivesicular endosomes (multivesicular bodies, MVB). Exosomes have a particular
      lipid and protein content, reflecting their origin as intraluminal vesicles of
      late endosomes. The stimulation of several hematopoietic cells induces the fusion
      of the limiting membrane of the MVB with the plasma membrane, leading to the
      release of exosomes towards the extracellular environment. In T lymphocytes,
      stimulation of the T cell receptor (TCR) induces the fusion of the MVBs with the
      plasma membrane and exosomes carrying several bio-active proteins are secreted.
      Among these proteins, the pro-apoptotic protein Fas ligand (FasL) is released as
      a non-proteolysed form (mFasL), associated to the exosomes. These mFasL-bearing
      exosomes may trigger the apoptosis of T lymphocytes. Here, we present evidences
      supporting a role of diacylglycerol kinase alpha (DGKalpha), a diacylglycerol
      (DAG)-consuming enzyme, on the secretion of exosomes carrying mFasL, and the
      subsequent activation-induced cell death (AICD) on a T cell line and primary T
      lymphoblasts.

PMID- 16989931
TI  - Effect of simulated pulpal pressure on all-in-one adhesive bond strengths to
      dentine.
AB  - OBJECTIVES: To evaluate the durability of all-in-one adhesive systems bonded to
      dentine with and without simulated hydrostatic pulpal pressure (PP). METHODS:
      Flat dentine surfaces of extracted human molars were prepared. Two all-in-one
      adhesive systems, One-Up Bond F (OBF) (Tokuyama Corp., Tokyo, Japan), and Fluoro
      Bond Shake One (FBS) (Shofu Co., Kyoto, Japan) were applied to the dentine
      surfaces under either a PP of 0 or 15cm H(2)O. Then, resin composite build-ups
      were made. The specimens bonded under pressure were stored in 37 degrees C water
      for 24h, 1 and 3 months under 15cm H(2)O PP. Specimens not bonded under pressure
      were stored under zero PP. After storage, the specimens were sectioned into slabs
      that were trimmed to hourglass shapes and subjected to micro-tensile bond testing
      (muTBS). The data were analysed using two-way ANOVA and Holm-Sidak HSD multiple
      comparison tests (alpha=0.05). RESULTS: The muTBS of OBF fell significantly
      (p<0.05) when PP was applied during bonding and storage, regardless of storage
      time. In contrast, although the muTBS of OBF specimens bonded and stored without
      hydrostatic pressure storage fell significantly over the 3 months period, the
      decrease was less than half as much as specimens stored under PP. In FBS bonded
      specimens, although there was no significant difference between the muTBS with
      and without hydrostatic pulpal pressure at 24h, by 1 and 3 months of storage
      under PP, significant reductions were seen compared with the control group
      without PP. CONCLUSION: The muTBS of OBF bonded specimens was lowered more by
      simulated PP than by storage time; specimens bonded with FBS were not sensitive
      to storage time in the absence of PP, but showed lower bond strengths at 1 and 3
      months in the presence of PP.

PMID- 16989933
TI  - Inhibition of plant amine oxidases by a novel series of diamine derivatives.
AB  - A series of N,N'-bis(2-pyridinylmethyl)diamines was synthesized and characterized
      for their inhibition effects towards plant copper-containing amine oxidase (EC
      1.4.3.6) and polyamine oxidase (EC 1.5.3.11), which mediate the catabolic
      regulation of cellular polyamines. Even though these enzymes catalyze related
      reactions and, among others, act upon two common substrates (spermidine and
      spermine), their molecular and kinetic properties are different. They also show a
      different spectrum of inhibitors. It is therefore of interest to look for
      compounds providing a dual inhibition (i.e. inhibiting both enzymes with the same
      inhibition potency), which would be useful in physiological studies involving
      modulations of polyamine catabolism. The synthesized diamine derivatives
      comprised from two to eight carbon atoms in the alkyl spacer chain. Kinetic
      measurements with pea (Pisum sativum) diamine oxidase and oat (Avena sativa)
      polyamine oxidase demonstrated reversible binding of the compounds at the active
      sites of the enzymes as they were almost exclusively competitive inhibitors with
      K(i) values ranging from 10(-5) to 10(-3)M. In case of oat polyamine oxidase, the
      K(i) values were significantly influenced by the number of methylene groups in
      the inhibitor molecule. The measured inhibition data are discussed with respect
      to enzyme structure. For that reason, the oat enzyme was analyzed by de novo
      peptide sequencing using mass spectrometry and shown to be homologous to
      polyamine oxidases from barley (isoform 1) and maize. We conclude that some of
      the studied N,N'-bis(2-pyridinylmethyl)diamines might have a potential to be
      starting structures in design of metabolic modulators targeted to both types of
      amine oxidases.

PMID- 16989934
TI  - Acid DNases and their interest among apoptotic endonucleases.
AB  - Apoptosis is characterized by cell shrinkage, nuclear condensation and
      internucleosomal DNA cleavage. Besides the central role of caspases and other
      proteases, cell death triggers DNA degradation so that DNases have an active role
      in apoptotic cell death. The best-characterized apoptotic DNase is CAD, a neutral
      Mg-dependent endonuclease. Its activity is regulated by its inhibitor, ICAD,
      which is cleaved by caspases. Other neutral DNases have been shown to cleave
      nuclear DNA in apoptotic conditions: endonuclease G, GADD. In cells, the
      cytosolic pH is maintained to 7.2, mostly due to the activity of the Na(+)/H(+)
      exchanger. In many apoptotic conditions, a decrease of the intracellular pH has
      been shown. This decrease may activate different acid DNases, mostly when pH
      decreases below 6.5. Three acidic DNases II are so far known: DNase II alpha,
      DNase II beta and L-DNase II, a DNase II, derived from the serpin LEI (Leukocyte
      Elastase Inhibitor). Their activation during cell death is discussed in this
      review.

PMID- 16989935
TI  - Accuracy of clinical assessment of infant heart rate in the delivery room.
AB  - Heart rate (HR) dictates intervention during neonatal resuscitation. Guidelines
      recommend that HR be assessed by auscultation or palpation. We compared HRs
      determined clinically with electrocardiography (ECG) in healthy newborns in the
      delivery room. Clinical assessment by 23 observers randomly allocated to assess
      HR by one of two methods in 26 infants, was found to be inaccurate and
      underestimate ECG HR. The mean difference between HR assessed by auscultation and
      palpation ECG and HR using methodology recommended by the Neonatal Resuscitation
      Programme was 14 and 22 beats per minute respectively.

PMID- 16989936
TI  - Effectiveness and long-term outcome of cardiopulmonary resuscitation in
      paediatric intensive care units in Spain.
AB  - OBJECTIVE: To analyse the immediate effectiveness of resuscitation and long-term
      outcome of children who suffered a cardiorespiratory arrest when admitted to
      paediatric intensive care units (PICU). DESIGN AND SETTING: Secondary analysis of
      data from an 18-month prospective, multicentre study analysing cardiorespiratory
      arrest in children in 16 paediatric intensive care units in Spain. PATIENTS AND
      METHODS: We studied 116 children between 7 days and 17 years of age. Data were
      recorded according to the Utstein style. Analysed outcome variables were
      sustained return of spontaneous circulation (ROSC), survival to hospital
      discharge and survival at 1 year. Neurological and general performance outcome
      was assessed by means of the Paediatric Cerebral Performance Category (PCPC) and
      the Paediatric Overall Performance Category (POPC) scales. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: In 80 patients (69%) ROSC was achieved and it was
      sustained > 20 min in 69 (59.5%). At one-year follow-up, 40 children (34.5%) were
      alive. Survival was not associated with sex, age or weight of patients. Mortality
      from cardiac arrest was higher than respiratory arrest (69.8% versus 40%, p =
      0.01). Patients with sepsis had a higher mortality than other diagnostic groups.
      Mechanically ventilated children and those treated with vasoactive drugs had a
      higher mortality. Initial mortality was slightly higher in patients with slow ECG
      rhythms (35.7%) compared to those with ventricular fibrillation (VF) or pulseless
      ventricular tachycardia (VT) (27.2%). Duration of resuscitation effort was
      correlated with mortality (p < 0.0001). Patients who required one or more doses
      of adrenaline had also a higher mortality (77.8% versus 20.7%, p < 0.0001) and
      survivors needed less doses of adrenaline (0.85 +/- 1.14 versus 4.4+/-2.9, p <
      0.0001). At hospital discharge 86.8 and 84.6% of patients had scores 1 or 2
      (normal or near-normal) in the PCPC and POPC scales. At 1-year follow-up these
      figures were 90.8 and 86.3%, respectively. CONCLUSION: One-third of children who
      suffer a cardiac or respiratory arrest when admitted to PICU survive, and most of
      them had a good long-term neurological and functional outcome. The duration of
      cardiopulmonary resuscitation attempts is the best indicator of mortality.

PMID- 16989937
TI  - Outcome of cardiopulmonary resuscitation in intensive care units in a university
      hospital.
AB  - The purpose of this study is to evaluate the demographic characteristics of
      patients who suffered cardiac arrest in our intensive care units (ICUs) as well
      as to identify those factors influencing outcome after resuscitation following
      cardiac arrest. METHODS: We reviewed the records of all patients who underwent
      cardiopulmonary resuscitation (CPR) in our ICUs at the Georg-August University
      Hospital, Goettingen, Germany, from January 1, 1999 to December 31, 2003.
      RESULTS: One hundred and sixty-nine patients underwent CPR. Severity of illness
      assessed by SAPS II score on admission was 51.8+/-18.5 (predicted mortality
      46.6%). The initially monitored rhythm at the time of arrest was asystole in 51
      (30.2%) patients. Ventricular tachycardia/fibrillation (VT/VF) was recorded in 65
      (38.5%) and pulseless electrical activity in 49 (29.0%) patients. Twenty (23.8%),
      28 (33.3%) and 33 (39.3%) patients with initially recorded asystole, VT/VF and
      pulseless electrical activity (PEA) rhythms, respectively, survived to ICU
      discharge. Eighty of the 169 patients survived to hospital discharge giving a
      survival rate of 47.3%. The highest ICU mortality was seen in patients admitted
      for neurosurgery (80%) followed by major vascular surgery (77.8%), non-surgical
      patients (67.4%) and patients with severe sepsis (66.7%). The occurrence of
      cardiac arrest within the first 24h was associated with a significantly lower ICU
      mortality compared to a later incident. At hospital discharge 66 patients (82.5%
      of the survivors) achieved good cerebral recovery, 12 patients (15.0%) were
      severely disabled (CPC 3) while 2 (2.5%) remained unconscious. CONCLUSION:
      Several factors affect the outcome from CPR. However, quicker triage to ICU,
      closer monitoring along with prompt intervention might minimise the consequences
      of cardiac arrest and its complications.

PMID- 16989938
TI  - Effects of lopinavir-ritonavir combined therapy during the rat pregnancy.
      Morphological and biochemical aspects.
AB  - OBJECTIVE: To evaluate the biochemical and morphological effects in rats
      subjected to three different dose associations of the protease inhibitors
      lopinavir and ritonavir administered throughout the entire period of pregnancy.
      STUDY DESIGN: The animals were treated throughout pregnancy with daily oral doses
      of lopinavir+ritonavir starting at the day one of pregnancy, and were divided
      into four groups: E1, 13.3+3.3 mg/kg; E2, 39.9+9.9 mg/kg; E3, 119.7+29.9 mg/kg
      and C, control (drug vehicle, propyleneglycol). The animals were then sacrificed
      and maternal blood and fetal and maternal organ samples were taken for
      morphological and biochemical analysis. RESULTS: No major changes were identified
      in the group treated with the lowest dose as compared with the control. In the
      group E2, we found hepatocytes with signs of atrophy, eosinophilic cytoplasm,
      picnotic nuclei and vasodilatation. The proximal convoluted tubules of maternal
      kidneys showed eosinophilic areas and hyperchromatic nuclei, as well as signs of
      vasodilation. In the group treated with the highest dose (group E3), in the
      maternal kidneys and livers, the morphological changes were similar to those
      found in E2, although more prominent. Regarding the fetal organs, the single
      abnormality observed was some liver vasodilation in the group E3 (highest dose).
      The treatment with lopinavir+ritonavir caused discrete, yet significant,
      alterations of aspartate aminotransferase activity, blood urea nitrogen and
      creatinine plasma levels. CONCLUSIONS: Our results showed that the administration
      of a combination of lopinavir plus ritonavir to pregnant rats can cause
      morphological as well as functional changes in maternal and fetal liver and
      kidneys and, in higher than therapeutic doses, might be toxic to those animals.

PMID- 16989939
TI  - Photophysics of ANS. IV. Electron transfer quenching of ANS in alcoholic solvents
      and mixtures.
AB  - ANS is observed to decay from the fluorescent state with distributed kinetics in
      nearly pure ethanol solvent, notwithstanding that in mixed ethanol/water solvents
      the decay is discrete and biexponential. The origin of this behavior is
      investigated. In particular, a theory of electron transfer theory in the
      adiabatic regime is adduced, with specific involvement of solvent cage structure
      in the form of the solvent-electron polaron wave function. Properties of various
      polarons for various solvent systems are predicted and, for the case of ethanol
      and cyclohexanol, employed to generate the observed Arrhenius-type decay
      parameters in a quantitative fashion.

PMID- 16989940
TI  - Towards the mechanism of trimeric purine nucleoside phosphorylases: stopped-flow
      studies of binding of multisubstrate analogue inhibitor - 2-amino-9-[2
      (phosphonomethoxy)ethyl]-6-sulfanylpurine.
AB  - The binding of multisubstrate analogue inhibitor - 2-amino-9-[2
      (phosphonomethoxy)ethyl]-6-sulfanylpurine (PME-6-thio-Gua) to purine nucleoside
      phosphorylase from Cellulomonas sp. at 20 degrees C, in 20 mM Hepes buffer with
      ionic strength adjusted to 50 mM using KCl, at several pH values between 6.5 and
      8.2, was investigated using a stopped-flow spectrofluorimeter. The kinetic
      transients registered after mixing a protein solution with ligand solutions of
      different concentrations were simultaneously fitted by several association
      reaction models using nonlinear least-squares procedure based on numerical
      integration of the chemical kinetic equations appropriate for given model. It is
      concluded that binding of a PME-6-thio-Gua molecule by each of the binding sites
      is sufficiently well described by one-step process, with a model assuming
      interacting binding sites being more probable than a model assuming independent
      sites. The association rate constants derived from experimental data, assuming
      one step binding and independent sites, are decreasing with an increase in pH,
      changing from 30 to 6 microM(-1)s(-1) per binding site. The dissociation rate
      constants are in the range of 1-3 s(-1), and they are rather insensitive of
      changes in pH. Interestingly, for each pH value, the one-step binding model with
      interacting sites results in the association rate constant per site 1.5-4 times
      smaller for the binding of the first ligand molecule than that for the binding of
      the second one. Decrease of association constants with pH indicate that the
      enzyme does not prefer binding of the naturally occurring anionic form of the 6
      thioguanine ring (pK(a) 8.7) resulting from a dissociation of N(1)-H. This
      finding supports the mechanism in which hydrogen bond interaction of N(1)-H with
      Glu204 (Glu 201 in mammalian PNPs) is crucial in the catalytic process. Results
      obtained also indicate that, in contrast to transition-state analogues, for which
      binding is followed by a conformational change, binding of multisubstrate
      analogue inhibitors to trimeric PNPs is a one-step process.

PMID- 16989941
TI  - Polyphenols dynamics and phytotoxicity in a soil amended by olive mill
      wastewaters.
AB  - The effects of unprocessed olive mill wastewaters (OMW) on soil characteristics
      were investigated. Phenolic compounds levels in the treated soil were compared to
      those of a control soil profile. Results showed that OMW infiltration caused a
      modification of soil physicochemical characteristics. Phenolic compounds were
      detected at a depth of 1.2m four months after the last application of OMW. A
      moderate phytotoxic residual phenolic fraction (F) was extracted from the
      superficial soil layer 1 year after the OMW application. This residual F had a
      phytotoxic potential comparable to that of 25-fold diluted OMW.

PMID- 16989942
TI  - Anatomy and preservation of accessory pudendal arteries in laparoscopic radical
      prostatectomy.
AB  - OBJECTIVE: The incidence of laparoscopically diagnosed accessory pudendal
      arteries (APAs) varies depending on how proactive the surgeon is to find them.
      Their preservation depends on their calibre and location. Our objective was to
      provide a detailed description of how to identify, dissect, and preserve APAs
      during laparoscopic radical prostatectomy (LRP). METHODS: Between January 2003
      and January 2005, we treated 377 men with LRP; 325 met inclusion criteria for
      this study. We defined an APA as any artery located within the periprostatic
      region running parallel to the dorsal vascular complex and extending caudally
      towards the anterior perineum, other than cavernous arteries, corona mortis, and
      satellite arteries to the superficial and deep vascular complex. Two distinct
      varieties of APAs were identified: (1) lateral APAs course along the lateral
      aspect of the prostate and branch off any of the terminal branches of the
      hypogastric artery; and (2) apical APAs emerge through the levator ani fibres
      near the apical region of the prostate and most likely branch off the pudendal
      artery or corresponds to an aberrant course of the pudendal artery itself. We
      present a video depicting the laparoscopic anatomy of APAs and the technique to
      preserve them. RESULTS: Ninety-six of 325 men (30%) were found to have 125
      separate APAs. Using the depicted surgical technique, we were able to preserve
      83% of all APAs. Forty-nine of 55 lateral APAs (89%) and 55 of 70 apical APAs
      (79%) were preserved. Thirty-five of 38 large-calibre APAs (92%) and 70 of 87
      small-calibre APAs (80%) were spared. The side-specific incidence of PSMs were 3%
      and 6% when APAs were preserved and not preserved, respectively (p=0.5).
      CONCLUSIONS: APAs are frequently identified during laparoscopic prostatectomy.
      Their preservation is feasible in LRP without increasing the risk of causing a
      PSM. It is reasonable to integrate APA preservation as part of the modern radical
      prostatectomy, although their role in functional outcomes still needs to be
      prospectively established.

PMID- 16989943
TI  - Cortisol can be pro- or anti-apoptotic in sea bream cells: potential role of
      HSP70 induction for cytoprotection.
AB  - Cortisol, and heat shock protein 70 (HSP70) are known to perform key roles as
      part of the fish stress response. In the present study, two in vitro systems were
      used to investigate a possible cortisol-HSP70-apoptosis regulatory relationship.
      Using a developed silver sea bream fibroblast cell line (SSF), cortisol was found
      to induce HSP70 synthesis with a concomitant protection against camptothecin
      induced apoptosis. The induction of HSP70 synthesis using azetidine was also
      found to protect SSF against apoptosis. A primary culture of silver sea bream
      macrophages (SSM) displayed reduced HSP70, underwent apoptosis and displayed
      reduced phagocytic activity upon exposure to cortisol. The effect of cortisol on
      HSP70 expression in both SSF and SSM were blocked by the glucocorticoid
      antagonist, RU486. Treatment of SSM with azetidine protected against apoptosis
      and also enhanced phagocytic activity. The data from this study demonstrates for
      the first time that cortisol can be either anti- apoptotic or pro-apoptotic in
      different fish cells and such actions can be mediated via HSP70 induction or
      suppression respectively.

PMID- 16989945
TI  - alpha-1 Adrenergic receptors stimulation induces the proliferation of neural
      progenitor cells in vitro.
AB  - The proliferation of neural progenitor cells (NPCs) is regulated by classical
      neurotransmitters such as dopamine, serotonin and acetylcholine, via its own
      receptors. Previous studies have reported that the depletion of L-norepinephrine
      decreases the proliferation of NPCs in the adult rat hippocampus and it has been
      suggested that L-norepinephrine regulates the proliferation of NPCs. However, it
      remains unknown whether or not adrenergic receptors are involved in the increased
      proliferation of NPCs. In the present study, an MTT cell proliferation assay was
      carried out in order to investigate the roles played by adrenergic receptors in
      the proliferation of NPCs. We demonstrated that L-epinephrine enhanced the
      proliferation of embryonic NPCs in vitro. In addition, the alpha-1 adrenergic
      receptor agonist L-phenylephrine was found to enhance the proliferation of NPCs,
      whereas an alpha-adrenergic antagonist and selective alpha-1 antagonists
      significantly inhibited cell proliferation increases induced by L-epinephrine and
      L-phenylephrine. These results suggest that stimulation with alpha-1 adrenergic
      receptors induces the proliferation of embryonic NPCs.

PMID- 16989944
TI  - SMRT recruitment by PPARgamma is mediated by specific residues located in its
      carboxy-terminal interacting domain.
AB  - The silencing mediator of retinoid and thyroid hormone receptors (SMRT) has been
      shown to play an important role in adipogenesis and PPARgamma transcriptional
      activity. SMRT contains two interacting domains that mediate interactions with
      nuclear receptors. Interestingly, SMRT is recruited to PPARgamma via its C
      terminal interacting domain, and mutation of the proximal interacting domain does
      not interfere with recruitment via PPARgamma. To understand how the distal
      interacting domain mediates recruitment by PPARgamma, we have now mutated
      residues in this domain to the corresponding amino acids found in the proximal
      domain. We show that specific residues in this distal domain are vital for
      interactions with PPARgamma, but not for a related receptor, RARalpha.
      Furthermore, naturally-occuring SMRT isoforms that differ in interacting domain
      sequences have different effects on PPARgamma as opposed to RARalpha recruitment.
      These data suggest that PPARgamma and RARalpha interact with SMRT via distinct
      mechanisms. These differences will be important as ligands are designed that lead
      to specific patterns of nuclear receptor recruitment of corepressors.

PMID- 16989946
TI  - Hippocampus protein profiling reveals aberration of malate dehydrogenase in
      chlorpromazine/clozapine treated rats.
AB  - Chlorpromazine and clozapine are antipsychotic agents used to relieve symptoms of
      early-diagnosed schizophrenia. In this study, we used proteomics technology to
      screen the protein aberration in Sprague-Dawley rats treated with these two
      antipsychotic agents. Our goal was to identify the effects of antipsychotics on
      hippocampal proteins in rats. Protein expression profiles were compared in each
      experimental group using two-dimensional gel electrophoresis and identified using
      matrix-assisted laser desorption/ionisation time of flight mass spectrometry.
      Malate dehydrogenase, peroxiredoxin 3, vacuolar ATP synthase subunit beta and
      mitogen-activated protein kinase kinase 1 were found to have altered expression
      levels in the groups treated with antipsychotics compared with the matched
      controls. These findings should contribute to identifying new targets for disease
      preventing pharmacological agents and be beneficial for the development of more
      effective agents.

PMID- 16989947
TI  - Speech across the menstrual cycle: a replication and extension study.
AB  - Whiteside et al. [S.P. Whiteside, A. Hanson, P.E. Cowell, Hormones and temporal
      components of speech: sex differences and effects of menstrual cyclicity on
      speech, Neurosci. Lett. 367 (2004) 44-47] documented effects of menstrual cycle
      phase and sex on voice onset time (VOT) in naturally timed speech using whole
      words. VOT is a temporal component of speech that plays an important role in
      production and perception [L.L. Koenig, Laryngeal factors in voiceless consonant
      production in men, women, and 5-year-olds, J. Speech Lang. Hear. Res. 43 (2000)
      1211-1228; A. Lofqvist, L.L. Koenig, R.S. McGowan, Vocal tract aerodynamics in
      /aCa/ utterances: measurements, Speech Commun. 16 (1995) 49-66; T.M. Nearey, B.
      Rochet, Effects of place of articulation and vowel context in VOT production and
      perception for French and English Stops, J. Int. Phon. Assoc. 24 (1994) 1-18;
      L.M. Rimol, T. Eichele, K. Hugdahl, The effect of voice-onset-time on dichotic
      listening with consonant-vowel syllables, Neuropsychologia 44 (2006) 191-196;
      P.G. Simos, R.L. Diehl, J.I. Breier, M.R. Molis, G. Zouridakis, A.C.
      Papanicolaou, MEG correlates of categorical perception of a voice onset time
      continuum in humans, Cogn. Brain Res. 7 (1998) 215-219; S.P. Whiteside, J.
      Marshall, Developmental trends in voice onset time: some evidence for sex
      differences, Phonetica 58 (2001) 196-210]. The present study was designed to
      replicate and expand upon Whiteside et al. [S.P. Whiteside, A. Hanson, P.E.
      Cowell, Hormones and temporal components of speech: sex differences and effects
      of menstrual cyclicity on speech, Neurosci. Lett. 367 (2004) 44-47] using a
      speeded syllable repetition paradigm. VOT measurements for 6 English plosives (/p
      b t d k g/) were obtained from speech samples of 15 women and 20 men (age 20-25
      years). Women were tested across two points in the menstrual cycle (Days 2-5: low
      estrogen and progesterone/low-EP; Days 18-25: high estrogen and progesterone/high
      EP) and men were tested once. Results indicated significant interaction between
      menstrual cycle phase and voicing (F(1,14)=8.239, P<0.02), whereby the voiced
      plosives (b, g) displayed shorter VOT values and the voiceless plosives (p, k)
      displayed longer values at the high-EP phase. Thus, the distinction between the
      voiced and voiceless plosive was enhanced at high-EP. Significant sex effects
      (F(1,33)=10.080, P<0.005) were seen with women at high-EP but not the low-EP
      phase having longer VOT values than men for voiceless plosives. Sex differences
      between the voiced and voiceless plosives were enhanced at the high-EP phase.
      This study indicates a role for activational ovarian hormones in regulating
      temporal features of speech in both whole words and speeded syllable repetition.

PMID- 16989948
TI  - The contrast-imaging function for tilted specimens.
AB  - A theoretical description of the contrast-imaging function is derived for tilted
      specimens that exhibit weak-phase object characteristics. We show that the tilted
      contrast-imaging function (TCIF) is a linear transformation, which can be
      approximated by the convolution operation for small tilt angles or for small
      specimens. This approximation is not valid for electron tomography, where
      specimen tilts are above 60 degrees and specimen dimensions amount to some 10
      microm. The approximation also breaks down for electron crystallography, where
      atomic resolution is to be achieved. Therefore, we do not make this approximation
      and propose a generalized algorithm for inverting the TCIF. The implications of
      our description are discussed in the context of electron tomography, single
      particle analysis, and electron crystallography, and the improved resolution is
      quantitatively demonstrated.

PMID- 16989949
TI  - Predicting milk-production responses after an autumn treatment of pastured dairy
      herds with eprinomectin.
AB  - The objectives of this study were (1) to determine the effect of a treatment with
      eprinomectin in autumn of pastured dairy herds on the anti-Ostertagia ostertagi
      bulk-tank milk antibody level, (2) to determine the overall effect of this
      treatment on three milk-production parameters (milk yield, protein % and fat %)
      and (3) to investigate the value of the pre-treatment Ostertagia-specific bulk
      tank milk antibody level to predict the production response after anthelmintic
      treatment. One hundred and nineteen herds in Flanders (Belgium) were randomly
      assigned to a treatment with eprinomectin or a placebo in October 2004. Bulk-tank
      milk samples were collected monthly from August 2004 until April 2005, and the
      antibody levels against O. ostertagi were determined as optical density ratios
      (ODRs) with an ELISA. The treatment effect over the 4 months following treatment
      on three production parameters (milk yield, milk-protein %, milk-fat %) was
      estimated by mixed models with herd as a random effect. The treatment effect on
      milk yield was also investigated within six categories of the pre-treatment ODR.
      The ODR values were lower in the eprinomectin group than in the control group at
      each time point after treatment. The overall effect on milk yield was estimated
      at 1.2 kg/cow/day, whereas no effect on the milk-protein % and milk-fat % was
      observed. Herds in the highest pre-treatment ODR category (>0.84) had a positive
      milk-yield response of 4.0 kg/cow/day (95%-confidence interval: 1.0; 7.0), while
      the 95%-confidence intervals of the milk-yield responses in the other categories
      all included zero. This study demonstrates that treatment with eprinomectin of
      pastured dairy cows in autumn will lower the Ostertagia-specific bulk-tank milk
      antibody level during the stabling period and can result in a consistent increase
      in milk yield. The results indicate that an O. ostertagi bulk-tank milk ELISA can
      be used to identify the herds where the greatest milk-yield response after an
      anthelmintic treatment is expected.

PMID- 16989950
TI  - Serodiagnosis of Neospora caninum infection in cattle using a recombinant tNcSRS2
      protein-based ELISA.
AB  - The truncated NcSRS2 gene (tNcSRS2) by removal of the N-terminal hydrophobic
      sequence was cloned into the pGEX-6p-1 plasmid and subsequently expressed as a
      glutathione-S-transferase (GST) fusion protein. The purified recombinant tNcSRS2
      protein was specific to Neospora caninum and was used in an ELISA for the
      diagnosis of neosporosis. There was a good agreement between tNctSRS2-based ELISA
      and three commercially available diagnostic kits (IDEXX ELISA, HIPRA ELISA and
      VMRD IFAT). Three hundred dairy cattle serum samples from 9 regions were tested
      by our ELISA. The herd prevalence was 100% and the overall prevalence was 20.3%.
      There was a statistically significant difference in seroprevalence between
      regions (P<0.01) and an association between abortion history and N. caninum
      seropositivity. Our study showed that neosporosis in dairy cattle is widespread
      in China.

PMID- 16989951
TI  - Comparison of serological methods for the diagnosis of Neospora caninum infection
      in cattle.
AB  - The aims of this study were to evaluate the performance and agreement of various
      commercial and in-house Neospora caninum antibody assays used in dairy cattle in
      North America, and to investigate reproducibility of two assays performed in
      different laboratories. From 1998 to 2005, three enzyme linked immunosorbent
      assays (ELISAs, a competitive ELISA-VMRD Inc., an indirect ELISA-Biovet Inc., and
      another indirect ELISA-Herdchek IDEXX Corp.), two indirect fluorescent antibody
      tests (IFATs, VMRD Inc., and in-house USDA) and one N. caninum agglutination test
      (NAT, in-house USDA) were utilized to test 397 randomly selected dairy cattle
      serum samples from 34 herds in eastern Canada for antibodies to N. caninum. The
      manufacturers' recommended cut-off values were used to evaluate test performance
      and agreement between tests. One IFAT (VMRD Inc.) performed well (sensitivity and
      specificity: 0.97 and 0.97, respectively) using reference sera (n = 452),
      therefore, results from this IFAT on the 397 samples could subsequently be used
      as the reference standard to calculate test characteristics for the other assays.
      Only 11% of the 397 sera were found to be N. caninum-positive with the IFAT.
      Prevalence-adjusted bias-adjusted kappa (PABAK) ranged from 0.06 to 0.99.
      Positive agreement was moderate to very good (P(pos) = 0.25-0.96). Negative
      agreement was very good for all assays (P(neg) > 0.94) except NAT (P(neg) =
      0.66). Sensitivity was > or =0.89 for all assays except the NAT, which had a
      significantly lower sensitivity (0.66). Specificity was high (>0.94) for all
      assays except for one indirect ELISA (specificity = 0.52). This indirect ELISA
      did not perform satisfactorily when used in 1998, but an improved version of the
      ELISA performed as one of the best assays in 2004. Reproducibility of the
      competitive ELISA was excellent, but the reproducibility of the indirect ELISA
      that was improved was low (concordance correlation coefficient = 0.90 and 0.36,
      respectively). The performance characteristics observed for most assays in this
      study make them useful for screening antibodies to N. caninum in cattle.

PMID- 16989952
TI  - DYX1C1 functions in neuronal migration in developing neocortex.
AB  - Rodent homologues of two candidate dyslexia susceptibility genes, Kiaa0319 and
      Dcdc2, have been shown to play roles in neuronal migration in developing cerebral
      neocortex. This functional role is consistent with the hypothesis that dyslexia
      susceptibility is increased by interference with normal neural development. In
      this study we report that in utero RNA interference against the rat homolog of
      another candidate dyslexia susceptibility gene, DYX1C1, disrupts neuronal
      migration in developing neocortex. The disruption of migration can be rescued by
      concurrent overexpression of DYX1C1, indicating that the impairment is not due to
      off-target effects. Transfection of C- and N-terminal truncations of DYX1C1 shows
      that the C-terminal TPR domains determine DYX1C1 intracellular localization to
      cytoplasm and nucleus. RNAi rescue experiments using truncated versions of DYX1C1
      further indicate that the C-terminus of DYX1C1 is necessary and sufficient to
      DYX1C1's function in migration. In conclusion, DYX1C1, similar to two other
      candidate dyslexia susceptibility genes, functions in neuronal migration in rat
      neocortex.

PMID- 16989953
TI  - Bacterial artificial chromosome transgenic analysis of dynamic expression
      patterns of regulator of G-protein signaling 4 during development. II.
      Subcortical regions.
AB  - A large family of regulator of G protein signaling (RGS) proteins modulates
      signaling through G-protein-coupled receptors. Previous studies have implicated
      RGS4 as a vulnerability gene in schizophrenia. To begin to understand structure
      function relationships, we have utilized bacterial artificial chromosome (BAC)
      methods to create transgenic mice that express green fluorescent protein (GFP)
      under the control of endogenous RGS4 enhancer elements, circumventing the lack of
      suitable antibodies for analysis of dynamic patterns of expression. This report
      follows from the accompanying mapping paper in cerebral cortex, with a focus on
      developmental and mature expression patterns in subcortical telencephalic,
      diencephalic and brainstem areas. Based on reporter distribution, the data
      suggest that alterations in RGS4 function will engender a complex phenotype of
      increased and decreased neuronal output, with developmental, regional, and
      cellular specificity.

PMID- 16989954
TI  - Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine
      phosphatase beta/phosphacan early in CNS development that localizes to
      extrasynaptic sites prior to synapse formation.
AB  - Perineuronal nets (PNs) are lattice-like condensations of the extracellular
      matrix (ECM) that envelop synapses and decorate the surface of subsets of neurons
      in the CNS. Previous work has suggested that, despite the fact that PNs
      themselves are not visualized until later in development, some PN component
      molecules are expressed in the rodent CNS even before synaptogenesis. In the
      adult mammalian brain, monoclonal antibody Cat-315 recognizes a glycoform of
      aggrecan, a major component of PNs. In primary cortical cultures, a Cat-315
      reactive chondroitin sulfate proteoglycan (CSPG) is also expressed on neuronal
      surfaces and is secreted into culture media as early as 24 h after plating. In
      this study, we show that in primary cortical cultures, the Cat-315 CSPG detected
      in early neural development is expressed in extrasynaptic sites prior to synapse
      formation. This suggests that ECM components in the CNS, as in the neuromuscular
      junction (NMJ), may prepattern neuronal surfaces prior to innervation. We further
      show that while the Cat-315-reactive carbohydrate decorates aggrecan in the
      adult, it decorates a different CSPG in the developing CNS. Using receptor
      protein tyrosine phosphatase beta (RPTPbeta/protein tyrosine phosphatase zeta)
      knock-out mice and immunoprecipitation techniques, we demonstrate here that in
      the developing rodent brain Cat-315 recognizes RPTPbeta isoforms. Our further
      examination of the Cat-315 epitope suggests that it is an O-mannose linked
      epitope in the HNK-1 family. The presence of the Cat-315 reactive carbohydrate on
      different PN components--RPTPbeta and aggrecan--at different stages of synapse
      development suggests a potential role for this neuron-specific carbohydrate motif
      in synaptogenesis.

PMID- 16989955
TI  - Anterograde tracing of projections from the dorsal raphe nucleus to the
      vestibular nuclei.
AB  - This study used the anterograde transport of biotinylated dextran amine (BDA) to
      identify the course and terminal distribution of projections from the dorsal
      raphe nucleus (DRN) to the vestibular nuclei in rats. After iontophoretic
      injection of BDA into the medial and lateral regions of DRN, anterogradely
      labeled fibers descend within the medial longitudinal fasciculus and the
      ventricular fiber plexus to terminate within two discrete regions of the
      vestibular nuclear complex. One terminal field was located primarily ipsilateral
      to the injection site and involved rostrodorsal aspects of the vestibular nuclei,
      including superior vestibular nucleus and rostral portions of the medial
      vestibular nucleus (MVN) and lateral vestibular nucleus (LVN). The other terminal
      field involved caudoventral aspects of both ipsilateral and contralateral MVN and
      LVN and was less heavily innervated. These findings confirm that the vestibular
      nuclei are targeted by a regionally-selective projection from the DRN. The
      segregation of DRN terminals into anatomically distinct fields indicates that the
      DRN-vestibular nucleus projections are organized to selectively modulate
      processing within specific functional domains of the vestibular nuclear complex.
      In particular, these terminal fields may be organized to modulate vestibular
      regions involved in eye movement-related velocity storage, coordination of
      vestibular and affective responses, and the bilateral coordination of horizontal
      eye movement reflexes.

PMID- 16989957
TI  - Treatment outcome for street-living, homeless youth.
AB  - Comprehensive intervention for homeless, street living youth that addresses
      substance use, social stability, physical and mental health issues has received
      very little attention. In this study, street living youth aged 14-22 were
      recruited from a drop-in center and randomly assigned to the Community
      Reinforcement Approach (CRA) or treatment as usual (TAU) through a drop-in
      center. Findings showed that youth assigned to CRA, compared to TAU, reported
      significantly reduced substance use (37% vs. 17% reduction), depression (40% vs.
      23%) and increased social stability (58% vs. 13%). Youth in both conditions
      improved in many other behavioral domains including substance use, internalizing
      and externalizing problems, and emotion and task oriented coping. This study
      indicates that homeless youth can be engaged into treatment and respond favorably
      to intervention efforts. However, more treatment development research is needed
      to address the barriers associated with serving these youth.

PMID- 16989956
TI  - Memantine protects against LPS-induced neuroinflammation, restores behaviorally
      induced gene expression and spatial learning in the rat.
AB  - Neuroinflammation is reliably associated with the pathogenesis of a number of
      neurodegenerative diseases, and can be detected by the presence of activated
      microglia. Neuroinflammation can be induced by chronic lipopolysaccharide (LPS)
      infusion into the 4th ventricle of the rat resulting in region-selective
      microglia activation and impaired hippocampal-dependent memory. Furthermore, this
      treatment results in altered behaviorally-induced expression of the immediate
      early gene Arc, indicating altered network activity. LPS is known to activate
      microglia directly, leading to increased glutamate release, and in enhanced N
      methyl-d-aspartate (NMDA) -dependent signaling. Taken together, the foregoing
      suggests that decreasing NMDA receptor activation during early stages of chronic
      neuroinflammation should reduce a) microglia activation, b) overexpression of
      Arc, and c) spatial memory deficits. Memantine, a low to moderate affinity open
      channel uncompetitive NMDA receptor antagonist, at low doses was used here to
      test these hypotheses. Rats were chronically infused into the 4th ventricle for
      28 days with LPS alone, vehicle alone (via osmotic minipump) or LPS and memantine
      (10 mg/kg/day memantine s.c.). The results reported here demonstrate that
      memantine reduces OX6-immunolabeling for activated microglia, spares resident
      microglia, returns Arc (activity-regulated cytoskeletal associated protein,
      protein) -expressing neuronal populations to control levels (as revealed by Arc
      immunolabeling and fluorescence in situ hybridization), and ameliorates the
      spatial memory impairments produced by LPS alone. These data indicate that
      memantine therapy at low doses, recreating plasma levels similar to those of
      therapeutic doses in human, acts in part through its ability to reduce the
      effects of neuroinflammation, resulting in normal gene expression patterns and
      spatial learning. Combined, these findings suggest that low, therapeutically
      relevant doses of memantine delivered early in the development of
      neuroinflammation-influenced diseases may confer neural and cognitive protection.

PMID- 16989958
TI  - The Drinking-Induced Disinhibition Scale (DIDS): a measure of three types of
      disinhibiting effects.
AB  - Links between trait disinhibition and high-risk drinking are well established. It
      is also known that alcohol has disinhibiting effects. Nonetheless, there is no
      measure in the literature devoted exclusively to assessing disinhibiting effects
      of alcohol. The multidimensional Drinking-Induced Disinhibition Scale (DIDS) was
      developed as part of Study I, a prospective survey conducted with undergraduates
      (N=337). Study II, a cross-sectional survey (N=260), allowed for a confirmatory
      factor analysis and further validation of the measure through comparisons with an
      expectancies scale. The nine-item DIDS is comprised of three subscales assessing
      euphoric/social, dysphoric and sexual disinhibition. All three subscales had good
      internal consistency and adequate test-retest reliability. Convergent and
      discriminant validity were established in both studies. The subscales had
      different associations with high-risk drinking: sexual disinhibition predicted
      heavy episodic drinking; dysphoric disinhibition predicted alcohol-related
      problems and euphoric/social had associations with both. A cluster analysis
      revealed four distinct disinhibition profiles (i.e., low effect drinker; high
      euphoric/social only; high euphoric social and dysphoric; high euphoric/social
      and sexual), which predicted likelihood of high-risk drinking.

PMID- 16989959
TI  - Florid monocytoid B-cell hyperplasia resembling nodal marginal zone B-cell
      lymphoma of mucosa associated lymphoid tissue type. A histological and
      immunohistochemical study of four cases.
AB  - A pale ring of medium-to-large cells surrounding the follicles, namely a marginal
      zone distribution pattern, is the key criterion for diagnosing nodal marginal
      zone B-cell lymphoma (NMZBL). The tumor cells of NMZBL occasionally exhibit the
      morphology of monocytoid B-cells (MBC). However, this condition can be difficult
      to distinguish from MBC hyperplasia in reactive conditions. We describe the
      histopathological and immunohistochemical findings of four cases exhibiting
      florid MBC hyperplasia and resembling NMZBLs. The patients consisted of three
      males and one female (age range 48-64 years) who had asymptomatic lymphadenopathy
      in the head and neck area. Histologically, a pale ring surrounding more than 75%
      of the lymphoid follicles characterizes the lesion. The lymphoid follicles
      usually had hyperplastic germinal centers, and progressive transformation of
      germinal center was noted in two cases. The pale ring was composed of medium-to
      large cells with indented or round nuclei and relatively abundant pale clear
      cytoplasm. Numerous plasma cells were observed in one case. The overall
      histomorphological findings in these four cases were similar to those of NMZBLs.
      However, immunohistochemical investigations demonstrated that MBCs were CD43- and
      bcl-2-. Moreover, immunohistochemistry, polymerase chain reaction, and flow
      cytometry studies demonstrated the polytypic nature of B-lymphocytes. Recognition
      of this unusual MBC hyperplasia in reactive lymph node lesions is important to
      avoid confusion with NMZBLs.

PMID- 16989960
TI  - Stealing of dunked food in Carib grackles (Quiscalus lugubris).
AB  - The use of tool or tool-like food processing behaviours can render animals
      vulnerable to theft (kleptoparasitism) because (1) large, nutritious items are
      usually involved, (2) value is added to the food due to long and/or complex
      handling, and (3) physical control of items is often temporarily lost during
      handling. In Barbados, Carib grackles (Quiscalus lugubris) immersing items in
      water before consumption (a behaviour known as food dunking) lose a larger
      proportion of items to conspecific food thieves than grackles that do not dunk.
      In this paper, we first show that dunking in Carib grackles functions as a proto
      tool food-processing technique that speeds up ingestion. We then examine five
      potential predictors of kleptoparasitism: only conspecific density and loss of
      physical control on food were found to influence the probability that birds would
      be attacked and successfully robbed of food by conspecifics. Grackles could
      reduce the probability of kleptoparasitism by holding items in the bill while
      dunking and engaging in head-up displays. These behaviours were used flexibly
      depending on variation in the risk of kleptoparasitism. We suggest that costs
      like the ones incurred from theft might limit the profitability and frequency of
      tool and proto-tool food processing behaviours, creating a context where counter
      strategies might be selected.

PMID- 16989961
TI  - Synonymous codon usage and its potential link with optimal growth temperature in
      prokaryotes.
AB  - The relationship between codon usage in prokaryotes and their ability to grow at
      extreme temperatures has been given much attention over the past years. Previous
      studies have suggested that the difference in synonymous codon usage between
      (hyper)thermophiles and mesophiles is a consequence of a selective pressure
      linked to growth temperature. Here, we performed an updated analysis of the
      variation in synonymous codon usage with growth temperature; our study includes a
      large number of species from a wide taxonomic and growth temperature range. The
      presence of psychrophilic species in our study allowed us to test whether the
      same selective pressure acts on synonymous codon usage at very low growth
      temperature. Our results show that the synonymous codon usage for Arg (through
      the AGG, AGA and CGT codons) is the most discriminating factor between
      (hyper)thermophilic and non-thermophilic species, thus confirming previous
      studies. We report the unusual clustering of an Archaeal psychrophile with the
      thermophilic and hyperthermophilic species on the synonymous codon usage
      factorial map; the other psychrophiles in our study cluster with the mesophilic
      species. Our conclusion is that the difference in synonymous codon usage between
      (hyper)thermophilic and non-thermophilic species cannot be clearly attributed to
      a selective pressure linked to growth at high temperatures.

PMID- 16989962
TI  - Characterization of two POU transcription factor family members from the
      urochordate Oikopleura dioica.
AB  - Three POU domain containing transcription factors have been cloned from the
      urochordate Oikopleura dioica. Phylogenetic analysis showed that two of these
      (OctA1 and OctA2) are closely related members of the class II POU domain family,
      and one (OctB) is a member of the class III POU domain family. All three
      transcription factors contained a highly conserved bipartite DNA-binding POU
      domain with POU specific and POU homeodomains, separated by a linker region. All
      three proteins were shown to bind specifically to the canonical octamer motif,
      ATGCAAAT. The ability of these factors to drive transcription from an octamer
      containing reporter construct was assessed in vertebrate B lymphocyte cell lines.
      Both OctA1 and OctA2 drove transcription in murine and catfish B cell lines,
      however, OctB did not increase the level of transcription above background
      levels. It is concluded that Oct transcription factors capable of functioning in
      a similar fashion to vertebrate Oct1/2 were present at the phylogenetic level of
      the urochordates.

PMID- 16989963
TI  - Control of human cytomegalovirus gene expression by differential histone
      modifications during lytic and latent infection of a monocytic cell line.
AB  - Non-differentiated THP-1 cells can be infected by human cytomegalovirus (HCMV)
      Towne strain, which persists in these cells in a non-active (latent) form without
      undergoing a productive cycle. The same cells become permissive for HCMV lytic
      infection after induction of cell differentiation by treatment with 12-O
      tetradecanoylphorbol-13-acetate. We used this cellular model to study the
      possible role of histone modifications in the control of HCMV latency. Using
      chromatin immunoprecipitation with antibodies against histone H3 acetylated or
      dimethylated in position K9, we demonstrated that in lytically infected cells the
      HCMV enhancer was associated with heavy acetylated but not dimethylated H3. In
      the case of latent infection, the HCMV enhancer was associated with neither
      acetylated nor dimethylated H3. HCMV genes encoding DNA polymerase (early), pp65
      (early-late) and pp150 (late) proteins were associated preferentially with
      acetylated H3 in lytically infected cells and with dimethylated H3 in latently
      infected cells. These data strongly suggest that K9 methylation of H3 is involved
      in HCMV gene repression, while association of the above genes with acetylated
      histones is likely to be necessary for active transcription. It can be postulated
      that the same histone modifications are used to mark active and repressed genes
      in both cellular and viral chromatin.

PMID- 16989964
TI  - Developmental changes of FSH-R, LH-R, ER-beta and GnRH-I expression in the ovary
      of prepubertal ducks (Anas platyrhynchos).
AB  - Normal ovarian development is dependent on stimulation of the gonadotropic
      hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), as
      well as some regulatory factors locally produced in ovary, e.g. 17beta-estradiol
      (E2) and gonadotropin-releasing hormone (GnRH), mediated by their respective
      receptors. In order to elucidate the potential roles of LH, FSH, E2 and GnRH-I
      during early follicular development in prepubertal ducks, mRNA expression of LH
      R, FSH-R, ER-beta and GnRH-I in ovaries of 1-day-old (D1), 30-day-old (D30), 60
      day-old (D60) and 90-day-old (D90) ducks was measured with semi-quantitative RT
      PCR using beta-actin as an internal standard. The ovary index (the ratio of ovary
      weight/body mass) did not change from D30 to D90, while the ovary weight and
      serum E2 levels rose progressively, indicating the prepubertal development of the
      ovary. Ovarian expression of FSH-R, LH-R, ER-beta and GnRH-I mRNA changed greatly
      during this period. Abundance of FSH-R and ER-beta mRNA went up gradually from D1
      to D60, followed by a decline on D90. LH-R and GnRH-I mRNA expression increased
      from D1 to D90, reaching a peak at D90. These results indicate that the
      developing ovary is highly responsive to the regulation of FSH during the early
      stage, while close to the onset of sexual maturation, the ovary is likely more
      responsive to LH. In addition, the expression of GnRH-I and ER-beta mRNA in the
      ovary suggest that GnRH-I and E2 are involved in the regulation of prepubertal
      follicular development in the ovary of ducks.

PMID- 16989965
TI  - Ovarian follicular and corpus luteum changes, progesterone concentrations, estrus
      and ovulation following estradiol benzoate/progesterone based treatment protocol
      in cross-bred cows.
AB  - The objectives of the present study were to investigate the effects of the stage
      of the estrous cycle at the start of an estradiol benzoate (EB) and progesterone
      (P) based treatment protocol on new follicular wave emergence, subsequent estrus
      and ovulation. The experiment was conducted using a crossover design with each
      cow (five cross-bred cows) being assigned to one of three groups at 3-month
      intervals within a 1-year period. Estrous cycle stage in individual cows was
      initially synchronized with prostaglandin F(2)alpha. After detection of estrus,
      each cow was injected intramuscularly (i.m.) with 2 mg EB and 200 mg P (EB/P) on
      day 5, 12 or 17 of the estrous cycle (estrus=day 0), followed by 1 mg EB i.m. 12
      days after the EB/P treatment. Ovarian ultrasonographic examinations showed that
      the emergence of a new follicular wave occurred after EB/P treatment in all
      groups and the mean interval from EB/P treatment to wave emergence did not differ
      among the groups (3.2-3.8 days). All cows in each group exhibited behavioral
      estrus and ovulated the newly formed dominant follicle. However, cows in the day
      17 group exhibited estrus 1-3 days before the second EB injection. The
      concentrations of progesterone showed faster reduction, during the treatment
      period, in the day-12 and -17 groups compared to the day-5 group. These results
      indicate that the EB/P treatment induces an emergence of a new follicular wave,
      irrespective of the estrous cycle stage at the start of treatment, but the effect
      of EB/P protocol on estrous/ovulation synchronization is influenced by the stage
      of the estrous cycle.

PMID- 16989966
TI  - Concentrations of free radicals and beta-endorphins in repeat breeder cows.
AB  - Repeat breeding (RB) is one of the major problems that affect the reproductive
      efficiency and economy of milk production in dairy animals. So far, the
      etiopathogenesis of this pathology has not been defined completely. Stress has
      been hypothesized to be a cause of impaired reproductive efficiency. Stress may
      cause an overproduction of beta-endorphins and free radicals; in particular,
      reactive oxygen species (ROS). The aim of this work is to determine the
      concentrations of these substances in RB cows and to evaluate the correlation
      with the serum level of progesterone. The study was performed on 60 dairy cows:
      26 RB and 34 control cows. Blood samples were collected on day 12 and day 16,
      after artificial insemination (AI) in all subjects, in order to assess the
      concentrations of progesterone, free radicals and beta-endorphins. The stressors,
      free radicals and beta-endorphins, that we considered, were higher in repeat
      breeders (day 12, 93.32(+/-1.91) UCarr and 0.50(+/-0.03) ng/ml; day 16, 94.42(+/
      1.91) UCarr and 0.61(+/-0.03) ng/ml), with a lower level of progesterone, which
      probably is responsible for failure to conceive. The stress factors (free
      radicals and beta-endorphins) may actually enhance each other and induce an
      inhibition of progesterone synthesis in repeat breeders.

PMID- 16989967
TI  - Herb medicine Yin-Chen-Hao-Tang ameliorates hepatic fibrosis in bile duct
      ligation rats.
AB  - The accumulation of hydrophilic bile acids in the liver is considered to play a
      pivotal role in the induction of hepatic injury. Yin-Chen-Hao-Tang (YCHT)
      decoction is an aqueous extract from three different herbs: Artemisia capillaries
      Thunb (Compositae), Gardenia jasminoides Ellis (Rubiaceae), Rheum officinale
      Baill (Polygonaceae), which has been recognized as a hepatoprotective agent for
      various types of liver diseases. Therefore, we used an experimental of biliary
      atresia model to test that YCHT plays a regulatory role in the pathogenesis of
      hepatic fibrosis. Hepatic damage with fibrosis was produced by common bile duct
      ligation (BDL) for 27 days in experimental cholestasis animal model. After
      surgery, YCHT (250 and 500mg/kg BW) oral administration once a day continued for
      27 days. BDL caused a prominent liver collagen deposition that was supported by
      the increased alpha-SMA protein and mRNA expression of procollagen I. YCHT
      significantly decreased hepatic alpha-SMA protein levels and decreased in
      hydroxyproline and thiobarbituric acid reactive substances (TBARS) levels of BDL
      rats. On the other hand, the normalizing effect of YCHT (250mg/kg) on the TGF
      beta1mRNA expression was independent on the dose of YCHT, 500mg/kg was not
      effectively changed the quantitative composition of mRNA levels. The study shows
      that hepatic hydroxyproline accumulation caused by hydrophilic bile acids
      accompanied by elevated hepatic lipid peroxidation, and hepatic collagen levels
      can be decreased in the presence of YCHT. In conclusion, long-term administration
      of YCHT in rats ameliorated the hydropholic bile acids induced hepatic injury
      that probably related to a reduced oxidant stress and degree of hepatic fibrosis.

PMID- 16989968
TI  - C(18) columns for the simultaneous determination of oxytetracycline and its
      related substances by reversed-phase high performance liquid chromatography and
      UV detection.
AB  - Simultaneous determination of oxytetracycline, 4-epioxytetracycline, alpha
      apooxytetracycline, tetracycline and beta-apooxytetracycline on C(18) columns has
      been accomplished using a high performance liquid chromatographic method with UV
      detection. Separation was achieved on a Hypersil BDS RP-C(18) column (250 mm x
      4.6 mm) and on a Waters C(18) Symmetry column (150 mm x 3.9mm), 5 microm particle
      size each. These columns were equilibrated with mobile phases consisted of
      methanol-acetonitrile-0.1M phosphate buffer pH 8.0 (12.5:12.5:75, v/v/v) and
      (15:15:70, v/v/v), respectively. The flow rate was 1.0 ml/min and the total
      elution time was 15 and 5 min, respectively. Both methods were applied to
      oxytetracycline raw material, human and veterinary formulations, where the
      excipients did not interfere. External standard calibration curves were linear
      for 4-epioxytetracycline, oxytetracycline, alpha-apooxytetracycline, tetracycline
      and beta-apooxytetracycline in the concentration range of 0.27-200 microM, 0.05
      200 microM, 0.03-200 microM, 0.35-200 microM and 0.20-200 microM on column A and
      0.08-200 microM, 0.15-200 microM, 0.09-200 microM, 0.25-200 microM and 0.47-200
      microM on column B, respectively. Day-to-day relative standard deviation of the
      determination for every component was less than 3%. Concerning the first column,
      limits of detection and quantification of the above compounds were in the
      concentration ranges of 10-106 nM and 30-352 nM, respectively, whereas on the
      second column these ranges became 27-144 nM and 81-475 nM, respectively. Recovery
      of the separated compounds was 95-105%.

PMID- 16989969
TI  - Quantitative analysis and chromatographic fingerprinting for the quality
      evaluation of Scutellaria baicalensis Georgi using capillary electrophoresis.
AB  - Quantitative analysis and chromatographic fingerprinting for the quality
      evaluation of a Chinese herb Scutellaria baicalensis Georgi using capillary
      electrophoresis (CE) technique was developed. The separation was performed with a
      50.0cm (42.0cm to the detector window)x75mum i.d. fused-silica capillary, and the
      CE fingerprint condition was optimized using the combination of central composite
      design and multivariate analysis. The optimized buffer system containing 15mM
      borate, 40mM phosphate, 15mM SDS, 15% (v/v) acetonitrile and 7.5% (v/v) 2
      propanol was employed for the method development, and the baseline separation was
      achieved within 15min. The determination of the major active components
      (Baicalin, Baicalein and Wogonin) was carried out using the optimized CE
      condition. Good linear relationships were provided over the investigated
      concentration ranges (the values of R(2): 0.9997 for Baicalin, 0.9992 for
      Baicalein, and 0.9983 for Wogonin, respectively). The average recoveries of these
      target components ranged between 96.1-105.6%, 98.6-105.2%, and 96.3-105.0%,
      respectively. CE fingerprints combined with the quantitative analysis can be used
      for the quality evaluation of S. baicalensis.

PMID- 16989970
TI  - Quantification and identification of polyomavirus DNA in blood and urine of renal
      transplant recipients.
AB  - A cohort of 201 kidney transplant recipients (KTR) including 7 patients with
      evidence of renal function deterioration (as defined by creatinine levels >20%
      over baseline values) was analyzed for polyomavirus DNA in blood and urine
      samples by a new quantitative polymerase chain reaction method. Of 201 patients,
      14 (6.9%) were positive for polyomavirus DNA in blood (median level, 500 copies
      per milliliter of blood) including all 7 patients with renal function
      deterioration. Polyomavirus DNA detection in blood for diagnosis of renal
      function deterioration in KTR showed a sensitivity of 100% and a specificity of
      96%, whereas positive and negative predictive values were 50% and 100%,
      respectively. Diagnostic value of decoy cells detection and polyomavirus DNA
      quantification in urine samples was negligible.

PMID- 16989971
TI  - Surgical wound infection associated with Psychrobacter phenylpyruvicus-like
      organism.
AB  - A case of surgical wound infection caused by Psychrobacter phenylpyruvicus-like
      organism is described. The strain showed phenotypic characteristics typical of P.
      phenylpyruvicus, but 16S rRNA sequencing showed 98.2% relatedness to Moraxella
      phenylpyruvica strain 752/52 and only 94.8% with P. phenylpyruvicus type strain
      ATCC 23333(T). The results of molecular analysis suggest that the strain we
      isolated may represent a new species within the genus Psychrobacter.

PMID- 16989972
TI  - WITHDRAWN: Yersinia enterocolitica identification in stool samples using real
      time PCR.
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- 16989973
TI  - Identification of an erm(T) gene in strains of inducibly clindamycin-resistant
      group B Streptococcus.
AB  - Five inducibly clindamycin (CLI)-resistant group B Streptococcus (GBS) isolates,
      all negative for erm(A) and erm(B) genes, were found to contain erm(T), a gene
      previously reported in erythromycin-resistant animal isolates of Lactobacillus
      spp. and human isolates of Streptococcus bovis. One additional GBS isolate,
      constitutively resistant to CLI, was also positive for the erm(T) gene in
      addition to erm(B). To our knowledge, this is the 1st report of erm(T) in GBS,
      the 2nd bacterial species from humans in which the erm(T) gene has been
      identified, and the 3rd erm gene to be found in GBS.

PMID- 16989974
TI  - Tigecycline (GAR-936) activity against Streptococcus gallolyticus (bovis) and
      viridans group streptococci.
AB  - Viridans group streptococci including Streptococcus gallolyticus (formerly S.
      bovis) represent serious invasive pathogens often associated with endocarditis or
      sepsis among immunocompromised or cancer patients. Tigecycline (GAR-936), the
      first clinically studied glycylcycline, has a potent gram-positive activity with
      a potential treatment option for these streptococcal infections. The studied
      collection (848 strains) included 100 isolates each of Streptococcus anginosus,
      Streptococcus constellatus, Streptococcus intermedius, Streptococcus mitis,
      Streptococcus oralis, Streptococcus salivarius, Streptococcus sanguis, and fewer
      strains of S. gallolyticus (98 strains) and Streptococcus mutans (50 strains).
      These strains were isolated from patients on 3 continents in the SENTRY
      Antimicrobial Surveillance Program and tested for susceptibility and interpreted
      by Clinical and Laboratory Standards Institute broth microdilution methods and
      criteria (< or = 0.25 microg/mL for tigecycline per US Food and Drug
      Administration). Penicillin susceptibility rates for the entire collection varied
      from 61% (S. sanguis) to 98% (S. constellatus), and macrolide susceptibility was
      also compromised (49-88%; average, 69%). Tigecycline was active against all
      isolates tested, in contrast to tetracycline resistance rates of 8-66%, and
      highest for S. gallolyticus. In conclusion tigecycline was quite active against
      bacteremic isolates of viridans group streptococci species and S. gallolyticus
      with an overall MIC90 at < or = 0.06 microg/mL; the highest MIC was only 0.25
      microg/mL.

PMID- 16989975
TI  - A LightCycler TaqMan assay for detection of Borrelia burgdorferi sensu lato in
      clinical samples.
AB  - Lyme disease (LD) is an infection caused by an ixodid tick-borne spirochete,
      Borrelia burgdorferi sensu lato. LD manifests itself as a multisystem
      inflammatory disease that affects the skin in its early localized stage and
      spreads to the joints, nervous system, heart, and, to a lesser extent, other
      organ systems in its later disseminated stages. If diagnosed and treated early
      with appropriate antibiotics, LD is almost always readily cured. Developing a
      highly sensitive and specific real-time polymerase chain reaction assay could be
      very useful in improving the diagnostic accuracy and decreasing turnaround time
      for results. We report the development of a LightCycler TaqMan assay targeting
      the OspA gene for clinical detection of B. burgdorferi sensu lato in various
      types of biologic samples. This assay was validated by testing a variety of
      clinical samples including cerebrospinal fluid, synovial fluid, skin biopsies,
      and blood and culture isolates from skin biopsies. The TaqMan testing results
      were 100% concordant with previously reported results. Reference strains
      representing isolates from other geographic regions were also successfully
      amplified. The developed assay is robust, is highly sensitive and specific for B.
      burgdorferi sensu lato, and is suitable for clinical detection of the bacterium
      in biologic samples.

PMID- 16989976
TI  - Molecular epidemiology and household transmission of community-associated
      methicillin-resistant Staphylococcus aureus in Hong Kong.
AB  - This study evaluated the clinical and epidemiologic features of individuals with
      community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in
      Hong Kong from January 2004 through December 2005. Twenty-four episodes of skin
      and soft tissue infections and 1 episode of meningitis due to CA-MRSA were
      identified. CA-MRSA infections or carriage was found in 6 (13%) of 46 household
      contacts. A total of 29 isolates were analyzed by the Staphylococcus cassette
      chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), and
      multilocus sequence typing. In addition, polymerase chain reaction detection of
      the genes encoding Panton-Valentine leukocidin was also carried out. It was
      observed that 24 had SCCmec IV/IVA and 5 had SCCmec V, and 23 were pvl positive.
      PFGE analysis clustered all except 1 isolate into 3 pulsed-field types (PFTs),
      HKU100 through HKU300. The HKU100 isolates had genotype ST30-IV identical to the
      Southwest Pacific clone. The HKU200 isolates belonged to ST59-V and were
      multiresistant, including an ermB-mediated macrolide resistance trait, which is
      characteristic of the predominant CA-MRSA clone in Taiwan. The HKU300 isolates
      had unique features (ST8, Panton-Valentine leukocidin negative, and SCCmec IVA)
      typical of CA-MRSA in Japan. In conclusion, CA-MRSA has a propensity to spread
      within families. Our findings showed that CA-MRSA strains in Hong Kong have
      diverse genetic backgrounds.

PMID- 16989977
TI  - Effects of bee venom on protease activities and free radical damages in synovial
      fluid from type II collagen-induced rheumatoid arthritis rats.
AB  - The effect of bee venom acupuncture (BVA) (api-toxin) on the development of type
      II collagen (CII)-induced arthritis (CIA) in rats has been studied. We have
      compared the levels of activity of a comprehensive range of cytoplasmic,
      lysosomal and matrix protease types, together with the levels of free radical
      induced protein damage (determined as protein carbonyl derivative) in synovial
      fluid from CIA-treated, BVA-treated and normal rats. Many protease types showed
      significantly increased activity in CIA compared with normal rats. BVA (5 and 10
      microl/100g) significantly reduced these enzyme activities by some 80% each, but
      levels of plasma proteases activity (including those enzyme types putatively
      involved in the immune response, such as dipeptidyl aminopeptidase IV and proline
      endopeptidase) in CIA, BVA (5 microl/100g)-treated and normal plasma samples were
      not significantly different. The level of free radical induced damage to synovial
      fluid proteins was approximately three-fold higher in CIA compared with normal
      rats. However, BVA (5 microl/100g) significantly decreased the level of reactive
      oxygen free radical species (ROS) induced oxidative damage to synovial fluid
      proteins. It was concluded that activation of proteolytic enzymes and free
      radicals are likely to be of equal potential importance as protein damaging
      agents in the pathogenesis of rheumatoid arthritis (RA), and the development of
      novel therapeutic strategies for the latter disorder should include both protease
      inhibitory and free radical scavenging elements. In addition, the protease
      inhibitory element should be designed to inhibit the action of a broad range of
      enzymatic mechanistic types (cysteine, serine, metallo proteinases and
      peptidases). In conclusion, BVA is considered to be an effective RA modulator,
      inhibiting protease activities and removing ROS.

PMID- 16989978
TI  - The sarcomeric myosin heavy chain gene family in the dog: analysis of isoform
      diversity and comparison with other mammalian species.
AB  - Sarcomeric myosin heavy chains (MyHC) are the major contractile proteins of
      cardiac and skeletal muscles and belong to class II MyHC. In this study the
      sequences of nine sarcomeric MyHC isoforms were obtained by combining assembled
      contigs of the dog genome draft available in the NCBI database. With this
      information available the dog becomes the second species, after human, for which
      the sequences of all members of the sarcomeric MyHC gene family are identified.
      The newly determined sequences of canine MyHC isoforms were aligned with their
      orthologs in mammals, forming a set of 38 isoforms, to search for the molecular
      features that determine the structural and functional specificity of each type of
      isoform. In this way the structural motifs that allow identification of each
      isoform and are likely determinants of functional properties were identified in
      six specific regions (surface loop 1, loop 2, loop 3, converter, MLC binding
      region, and S2 proximal segment).

PMID- 16989979
TI  - Endocrine and cytokine responses in humans with pulmonary tuberculosis.

PMID- 16989980
TI  - A novel immune-to-CNS communication pathway: cells of the meninges surrounding
      the spinal cord CSF space produce proinflammatory cytokines in response to an
      inflammatory stimulus.
AB  - Pain is enhanced in response to elevations of proinflammatory cytokines in spinal
      cerebrospinal fluid (CSF), following either intrathecal injection of these
      cytokines or intrathecal immune challenge with HIV-1 gp120 that induces cytokine
      release. Spinal cord glia have been assumed to be the source of endogenous
      proinflammatory cytokines that enhance pain. However, assuming that spinal cord
      glia are the sole source of CSF cytokines may be an underestimate, as the
      cellular composition of the meninges surrounding the spinal cord CSF space
      includes several cell types known to produce proinflammatory cytokines. The
      present experiments provide the first investigation of the immunocompetent nature
      of the spinal cord meninges. Here, we explore whether rat meninges are responsive
      to intrathecal gp120. These studies demonstrate that: (a) intrathecal gp120
      upregulates meningeal gene expression of proinflammatory signals, including tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin 6
      (IL-6), and inducible nitric oxide synthase (iNOS), and (b) intrathecal gp120
      induces meningeal release of TNF-alpha, IL-1beta, and IL-6. In addition,
      stimulation of isolated meninges in vitro with gp120 induced the release of TNF
      alpha and IL-1beta, indicating that the resident cells of the meninges are able
      to respond without immune cell recruitment. Taken together, these data document
      that the meninges are responsive to immunogenic stimuli in the CSF and that the
      meninges may be a source of immune products detected in CSF. The ability of the
      meninges to release to proinflammatory signals suggests a potential role in the
      modulation of pain.

PMID- 16989982
TI  - Modeling of autonomous problem solving process by dynamic construction of task
      models in multiple tasks environment.
AB  - Traditional reinforcement learning (RL) supposes a complex but single task to be
      solved. When a RL agent faces a task similar to a learned one, the agent must re
      learn the task from the beginning because it doesn't reuse the past learned
      results. This is the problem of quick action learning, which is the foundation of
      decision making in the real world. In this paper, we suppose agents that can
      solve a set of tasks similar to each other in a multiple tasks environment, where
      we encounter various problems one after another, and propose a technique of
      action learning that can quickly solve similar tasks by reusing previously
      learned knowledge. In our method, a model-based RL uses a task model constructed
      by combining primitive local predictors for predicting task and environmental
      dynamics. To evaluate the proposed method, we performed a computer simulation
      using a simple ping-pong game with variations.

PMID- 16989981
TI  - Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic
      mechanism of action.
AB  - BACKGROUND: Valproic acid (VPA) exposure in utero has been associated with an
      increased risk of both neural tube defects and autism spectrum disorders (ASDs).
      The terata induced by VPA suggest interference with pattern formation. Retinoic
      acid produces similar terata and is known to act in part by increasing the
      expression of Hoxa1. We tested the hypotheses that exposure to VPA would alter
      the expression of Hoxa1 in rat embryos during times of normal Hoxa1 expression
      (d10.5-13.5) and that exposure at earlier and later stages would induce
      inappropriate expression. METHOD: Hoxa1 expression levels were determined by real
      time PCR in individual embryos 1 h after exposure on gestational d10, 12, 13, 14,
      or 15. Additionally, teratogenic (4-yn-VPA) and nonteratogenic analogs of VPA (IE
      VPA), retinoic acid (RA), and saline were compared for effects on Hoxa1
      expression on d12. Embryos were allowed to develop for 1, 2, 4, 6, or 24 h, to
      follow the time course of effects. RESULTS: In utero exposure to VPA on
      gestational d10 and on d12-14 significantly increased the level of Hoxa1
      expression compared to saline-exposed embryos at developmental ages prior to,
      during and after the normal expression period for this gene. On gestational d12,
      exposures to VPA and 4-yn-VPA significantly increased Hoxa1 expression at all
      sacrifice times, compared to saline-exposed embryos. RA significantly elevated
      Hoxa1 expression at all time points except 24-h post-treatment. The
      nonteratogenic VPA analog, IE-VPA, did not affect Hoxa1 expression. CONCLUSIONS:
      VPA and 4-yn-VPA exposures elevated Hoxa1 mRNA during its normal expression
      period and induced expression outside of the normal period. This may explain, in
      part, how VPA disrupts development.

PMID- 16989983
TI  - Recurrent neural network architecture with pre-synaptic inhibition for
      incremental learning.
AB  - We propose a recurrent neural network architecture that is capable of incremental
      learning and test the performance of the network. In incremental learning, the
      consistency between the existing internal representation and a new sequence is
      unknown, so it is not appropriate to overwrite the existing internal
      representation on each new sequence. In the proposed model, the parallel pathways
      from input to output are preserved as possible, and the pathway which has emitted
      the wrong output is inhibited by the previously fired pathway. Accordingly, the
      network begins to try other pathways ad hoc. This modeling approach is based on
      the concept of the parallel pathways from input to output, instead of the view of
      the brain as the integration of the state spaces. We discuss the extension of
      this approach to building a model of the higher functions such as decision
      making.

PMID- 16989984
TI  - Neural voting machines.
AB  - A "Winner-take-all" network is a computational mechanism for picking an
      alternative with the largest excitatory input. This choice is far from optimal
      when there is uncertainty in the strength of the inputs, and when information is
      available about how alternatives may be related. For some time, the Social Choice
      community has recognized that many other procedures will yield more robust
      winners. The Borda Count and the pair-wise Condorcet tally are among the most
      favored. If biological systems strive to optimize information aggregation, then
      it is of interest to examine the complexity of networks that implement these
      procedures. We offer two biologically feasible implementations that are
      relatively simple modifications of classical recurrent networks.

PMID- 16989985
TI  - Single trial-based prediction of a go/no-go decision in monkey superior
      colliculus.
AB  - While some decision-making processes often result in the generation of an
      observable action, for example eye or limb movements, others may prevent actions
      and occur without an overt behavioral response. To understand how these decisions
      are made, one must look directly at their neuronal substrates. We trained two
      monkeys on a go/no-go task which requires a saccade to a peripheral cue stimulus
      (go) or maintenance of fixation (no-go). We performed binary regressions on the
      activity of single neurons in the superior colliculus (SC), with the go/no-go
      decision as a predictor variable, and constructed a virtual decision function
      (VDF) designed to provide a good estimation of decision content and its timing in
      a single trial decision process. Post hoc analyses by VDF correctly predicted the
      monkey's choice in more than 80% of trials. These results suggest that monitoring
      of SC activity has sufficient capacity to predict go/no-go decisions on a trial
      by-trial basis.

PMID- 16989986
TI  - Epstein-Barr virus latent membrane protein 1 mediates phosphorylation and nuclear
      translocation of annexin A2 by activating PKC pathway.
AB  - We have previously combined phosphorylation enrichment with proteomics technology
      to elucidate the novel phosphoproteins in the signaling pathways triggered by
      Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) and shown that
      LMP1 can increase the phosphorylation level of annexin A2. Here, we further
      showed that LMP1 increased the serine, but not tyrosine, phosphorylation of
      annexin A2 by activating a novel signaling pathway, the protein kinase C (PKC)
      signaling pathway. However, LMP1 did not affect the level of annexin A2
      expression. In addition, we found that LMP1 induced the nuclear entry of annexin
      A2 in an energy- and temperature-dependent manner, suggesting that the nuclear
      entry of annexin A2 is an active process. Treatment of LMP1-expressing cells with
      the PKC inhibitor myr-psiPKC resulted in annexin A2 being present almost
      exclusively at cell surface, instead of within the nucleus, suggesting that the
      nuclear entry of annexin A2 was associated with serine phosphorylation mediated
      by PKC.

PMID- 16989987
TI  - Prospective study of falls in long-term inpatients with chronic psychotic
      disorders.

PMID- 16989988
TI  - Effects of the novel 5-HT(6) receptor antagonist RO4368554 in rat models for
      cognition and sensorimotor gating.
AB  - Serotonin(6) (5-HT(6)) receptors are almost exclusively located in the central
      nervous system. High expression in the hippocampus, nucleus accumbens and
      striatum is consistent with a potential role in cognition and psychosis. The
      availability of potent, selective and brain-penetrating 5-HT(6) antagonists such
      as RO4368554 allows further characterization of the role of the 5-HT(6) receptor
      in these processes. Herein, we tested RO4368554 in several cognition tasks, as
      well as sensorimotor gating tests. Using scopolamine-impaired and unimpaired
      adult male rats, RO4368554 was given in novel object discrimination, social
      recognition, social discrimination, Morris water maze, passive avoidance and
      autoshaping procedures. RO4368554 reversed the effects of scopolamine in novel
      object discrimination (active doses in mg/kg, i.p., 3, 10), social recognition
      (3, 10), social discrimination (1, 3, 10) and passive avoidance (10, 30 i.p. and
      100 p.o.) tasks. In unimpaired rats, RO4368554 enhanced object discrimination (3,
      10; 4-h forgetting interval) and autoshaping learning (3), but was inactive in a
      water maze task (doses tested: 1-10 mg/kg, i.p.). In tests sensitive to
      antipsychotics, RO4368554 did not reverse sensorimotor gating deficits induced by
      the psychostimulants dizocilpine and amphetamine (doses tested: 1-30 mg/kg, i.p.)
      or neonatal lesion of the ventral hippocampus (1-10 mg/kg, i.p.). In conclusion,
      RO4368554 enhanced learning and memory processes in unimpaired and scopolamine
      impaired rats, supporting the notion that the cognitive enhancing effects of 5
      HT(6) receptor antagonists involve modulation of cholinergic neurotransmission.

PMID- 16989989
TI  - Syndecan-4 dependent FGF stimulation of mouse vibrissae growth.
AB  - The development, maintenance and regeneration of epithelial appendages such as
      hairs or vibrissae depend on reciprocal interactions between the epidermal and
      the dermal components of the integument. Growth factors are among a number of
      signaling molecules that have been identified during these developmental events.
      Growth factors such as fibroblast growth factors (FGFs) bind cell surface heparan
      sulfate proteoglycans (HSPGs) on their heparan sulfate side chains and as such
      these proteoglycans act as co-receptors for FGF receptors (FGFRs) by forming a
      ternary signaling complex of HSPG, FGFR and FGF. The syndecans make up a family
      (syndecan-1-4) of transmembrane HSPGs. In the present study we examined the
      growth response of mouse vibrissae to HSPG-binding growth factors as a function
      of the presence or absence of syndecan-4 in an organ culture system. Syndecan-4
      is expressed on keratinocytes that make up the inner root sheath of the vibrissa.
      Vibrissae from wild-type mice, but not from syndecan-4 null mice, displayed a
      statistically significant and dose-dependent growth response to FGF-1, FGF-2 and
      FGF-7. In contrast, a statistically significant growth response is seen in
      vibrissae from both wild-type and syndecan-4 null mice when the culture medium is
      supplemented with either hepatocyte growth factor (HGF) that binds to HSPG,
      insulin that does not bind to HSPG or 5% fetal bovine serum. The syndecan-4
      dependent effect of FGF-1, -2 and -7 on the transcriptional activity of IRS
      expressed genes and of genes involved in cell proliferation reveals a number of
      different response patterns. In vivo, the vibrissae of syndecan-4 null mice are
      shorter and have a smaller diameter than those of wild-type mice and this
      phenotype may result from a suboptimal response to growth factors. Syndecan-1,
      which is expressed in the outer root sheath of the vibrissae shaft, does not
      influence the response of the vibrissae to FGF-1, -2 and -7 and the length and
      diameter of vibrissae of syndecan-1 null mice do not differ from those of wild
      type mice.

PMID- 16989990
TI  - Electrokinetic flow in an elliptic microchannel covered by ion-penetrable
      membrane.
AB  - The electrokinetic flow of an electrolyte solution in an elliptical microchannel
      covered by an ion-penetrable, charged membrane layer is examined theoretically.
      The present analysis extends previous results in that a two-dimensional problem
      is considered, and the system under consideration simulates the flow of a fluid,
      for example, in a microchannel of biological nature such as vein. The
      electroosmostic volumetric flow rate, the total electric current, the streaming
      potential, and the electroviscous effect of the system under consideration are
      evaluated. We show that, for a constant hydraulic diameter, the variations of
      these quantities as a function of the aspect ratio of a microchannel may have a
      local minimum or a local maximum at a medium level of ionic strength, which
      depends on the thickness of the membrane layer. For a constant cross-sectional
      area, the electroosmostic volumetric flow rate, the total electric current, and
      the streaming potential increase monotonically with the increase in the aspect
      ratio, but the reverse is true for the electroviscous effect.

PMID- 16989991
TI  - DBA/2 mouse skin is unresponsive to dermal tumor promotion by cigarette smoke
      condensate.
AB  - Previous studies demonstrated that repetitive application of cigarette smoke
      condensate (CSC) to 7,12-dimethylbenz[a]anthracene (DMBA)-initiated SENCAR mouse
      skin for 29 weeks at doses of 10, 20 and 40 mg "tar"/application results in time-
      and dose-dependent dermal tumor formation. To evaluate CSC-induced tumor
      promotion in other mouse skin models, male DBA/2 mice were treated with N-methyl
      N'-nitro-N-nitrosoguanidine (MNNG) (300 microg) or DMBA (75 or 150 microg)
      followed by promotion with 1R4F CSC at concentrations ranging from 9 to 45 mg
      "tar"/application. Both MNNG and DMBA have previously been shown to adequately
      initiate tumor development. Study end-points included clinical signs, body
      weights, and mass tracking. Neither the DMBA-initiated/acetone-promoted control
      groups, nor DMBA-initiated/CSC-promoted groups produced grossly observable skin
      tumors. For MNNG-initiated groups, a total of four tumors were observed. Based on
      these findings, it would appear the DBA/2 mouse was unresponsive to CSC dermal
      tumor promotion. It is not possible, based on the study design employed, to
      determine the underlying basis for the apparent resistance exhibited by this
      mouse strain to CSC-induced tumor promotion.

PMID- 16989992
TI  - Modes of reproduction of the hybridogenetic fish Squalius alburnoides in the Tejo
      and Guadiana rivers: an approach with microsatellites.
AB  - The Squalius alburnoides complex was produced by hybridization between female S.
      pyrenaicus (PP genome) and an hypothetical paternal ancestor related with
      Anaecypris hispanica (AA genome). This study examined a diversity of mating types
      and found that there is the potential for considerable gene exchange among
      diploid, triploid and tetraploid hybrids. Using microsatellites, genomes were
      attributed to Squalius pyrenaicus (P) or reconstituted "nuclear non-hybrid"S.
      alburnoides (A), and subsequently confirmed in hybrids. Recombination of AA
      genomes in the "nuclear non-hybrid males" and recombination of the homogametic
      genomes (AA or PP) after exclusion of the heterogametic genome in triploid
      females (PAA) were observed by analysing parents and progeny of breeding
      experiments. Reproduction of tetraploids, generating a symmetric tetraploid
      genotype (PPAA) in the progeny, suggests a process that could potentially lead to
      the formation of a new bisexual species. Present results also support: (i)
      previously hypothesized pathways, in which PPA S. alburnoides females exclude the
      A genome, exhibit meiotic recombination between the P genomes and generate
      haploid eggs; (ii) reconstitution of the diploid maternal ancestor genome (PP) as
      well as of the unknown paternal ancestor (AA); (iii) the occurrence of the same
      genomic reproductive mechanisms when Anaecypris hispanica is involved; and (iv)
      the existence of an A. hispanica-like ancestor as the paternal ancestor of S.
      alburnoides.

PMID- 16989993
TI  - Critical look at the clinical practice guidelines for allergic rhinitis.
AB  - Allergic rhinitis (AR) is a major health concern and numerous guidelines have
      been developed to standardize and to improve the management of this disease. As
      in many other areas of medicine, the methodology of the AR guidelines has evolved
      from opinion-based to evidence-based medicine. Although evidence-based medicine
      has many benefits, it also has limitations and cannot cancel the value of the
      individual clinical expertise. More important than the methodology of guideline
      development is the efficacy of guidelines to change patient and physician
      behaviour and to improve clinical outcomes. At present, however, studies on the
      effectiveness of guidelines are few. The International Consensus on Rhinitis from
      1994 is the only guideline for AR that has been assessed for its effects on
      health outcomes. Furthermore, there is a lack of valid and reliable instruments
      to assess physician's and patient's attitude towards and compliance with
      guideline recommendations. There is no single effective way to ensure the use of
      guidelines into practice, but a carefully developed and multifaceted
      dissemination and implementation strategy and targeting and adapting guideline
      recommendations to the local and individual level are key elements. The final and
      most important step of putting guidelines into practice occurs at the level of
      the patient. Patients should be considered as effective partners in health care.
      Education of the patient and efforts to change patient's behaviour can maximize
      compliance, increase satisfaction and optimize health outcomes.

PMID- 16989994
TI  - Biology and management of malignant pleural mesothelioma.
AB  - Malignant mesothelioma is an aggressive tumour, with a poor prognosis and an
      increasing incidence as a result of widespread exposure to asbestos. The results
      of the treatments available are poor. Surgery and radiotherapy have a limited
      role in highly selected patients and systemic therapy is the only potential
      treatment option for the majority of patients. Despite some definite activity of
      the novel antifolates such as pemetrexed and raltitrexed, the results, even in
      combination with platinating agents, are still modest, with a median survival of
      approximately one year. The better understanding of the biology of mesothelioma
      makes the assessment of a number of targeted agents particularly interesting.
      Unfortunately, the targeted agents imatinib, gefitinib, erlotinib and thalidomide
      have been shown to be ineffective in unselected patients. Studies with anti
      angiogenesis agents are ongoing. An improvement of the knowledge of major
      molecular pathways involved in malignant mesothelioma is needed in order to
      define proper targets for the systemic treatment of this disease.

PMID- 16989995
TI  - Follow-up after childhood cancer: evaluation of a three-level model.
AB  - INTRODUCTION: Follow-up for cancer survivors is recommended to detect recurrence;
      monitor late-effects; record toxicity and provide care and education. We describe
      our experience with a three-level model developed to guide decisions about
      intensity and frequency of follow-up [Wallace WHB, Blacklay A, Eiser C, et al.
      Developing strategies for the long term follow-up of survivors of childhood
      cancer. BMJ 2001;323:271-274]. PROCEDURE: One hundred and ninety eight survivors
      (52% male) recruited over 12-months: (mean age=23.8 years, range=16-39 years;
      mean time since diagnosis=16.2 years, range 2.4-32.7 years) reported their number
      of symptoms and late-effects. Information was taken from the medical records to
      assign each survivor to the appropriate levels by six clinic staff independently.
      RESULTS: The survivors were assigned to level 1 (n=8), level 2 (n=97) and level 3
      (n=93). There were seven cases of disagreement. Level 3 survivors self-reported
      more symptoms and late-effects than level 2 survivors. CONCLUSIONS: Coding was
      relatively simple for experienced clinic staff, although there were some
      disagreements for the survivors of ALL. The relationship between assigned level
      and self-reported symptoms and late-effects provides some evidence for validity
      of the model. We conclude that it is important to maintain flexibility to allow
      movement between levels for individual patients and that the default should
      always be to the higher level.

PMID- 16989996
TI  - Reduced mortality for women with mammography-detected breast cancer in east
      Denmark and south Sweden.
AB  - The 5-year relative survival from breast cancer in Denmark is 10 percentage
      points lower than in Sweden. This difference has been demonstrated previously as
      being caused partly by more involved lymph nodes and larger tumours in Denmark.
      Sweden has had nationwide mammography-screening coverage since 1991, whereas this
      is still in its infancy in Denmark. In the search for an explanation for the
      remaining survival difference, patient delay was a likely candidate. This study
      compared patient delay and mammography-detection between two national regions.
      Data on patient delay and mammography were obtained from hospital records from
      1989 and 1994, and analysed using Cox proportional hazard analysis of death
      within the first 5 years, with the factors age, country, delay/mammography
      detection and established patho-anatomic variables. A comparison of patient delay
      and mammography detection in 1989 and 1994 showed more mammography-detected
      tumours in south Sweden and more women with long delay in east Denmark.
      Mammography detection, but not long patient delay, had a significant effect on
      the death hazard when adjusting for patho-anatomic risk factors. The hazard ratio
      was not eliminated in 1989, but in 1994, the hazard ratio between east Denmark
      and south Sweden was reduced from 1.3 to 1.1. In conclusion, patient delay did
      not appear to have any effect on 5-year survival when adjusting for patho
      anatomic factors, but tumour detection by mammography affected survival
      favourably and partly explained the survival difference between east Denmark and
      south Sweden.

PMID- 16989998
TI  - Three-dimensional quantitative structure-activity relationship (3 D-QSAR) and
      docking studies on (benzothiazole-2-yl) acetonitrile derivatives as c-Jun N
      terminal kinase-3 (JNK3) inhibitors.
AB  - Three-dimensional quantitative structure-activity relationship (3D-QSAR) models
      were developed for 44 (benzothiazole-2-yl) acetonitrile derivatives, inhibiting c
      Jun N-terminal kinase-3 (JNK3). It includes molecular field analysis (MFA) and
      receptor surface analysis (RSA). The QSAR model was developed using 34 compounds
      and its predictive ability was assessed using a test set of 10 compounds. The
      predictive 3D-QSAR models have conventional r2 values of 0.849 and 0.766 for MFA
      and RSA, respectively; while the cross-validated coefficient r(cv)2 values of
      0.616 and 0.605 for MFA and RSA, respectively. The results of the QSAR model were
      further compared with a structure-based analysis using docking studies with
      crystal structure of JNK3. Ligands bind in the ATP pocket and the hydrogen bond
      with GLN155 was found to be crucial for selectivity among other kinases. The
      results of 3D-QSAR and docking studies validate each other and hence, the
      combination of both methodologies provides a powerful tool directed to the design
      of novel and selective JNK3 inhibitors.

PMID- 16989997
TI  - High inter-observer agreement in immunohistochemical evaluation of HER-2/neu
      expression in breast cancer: a multicentre GEFPICS study.
AB  - The accurate determination of HER-2 in invasive breast cancer has become a
      critical issue, particularly in the context of the results of recent trastuzumab
      (Herceptin((R))) adjuvant trials. This multicentre study evaluated inter-observer
      reproducibility in interpretation of HER-2 immunostains performed in different
      laboratories according to their in-house technique. A total of 74 HER-2
      immunostains were evaluated by 16 pathologists and by a central review committee.
      As determined by central review, the HER-2 score was 0 in 33 cases (44%), 1+ in
      10 cases (13%), 2+ in 9 cases (12%) and 3+ in 23 cases (31%). The overall kappa
      value was good (kappa=0.75). Agreement was excellent for the 0/1+ group
      (kappa=0.85) and for the 3+ group (kappa=0.82). As expected, the score 2+ group
      showed poor agreement (kappa=0.38). A quality assurance process showed that ring
      studies and adherence to national guidelines greatly improve inter-observer
      reproducibility.

PMID- 16989999
TI  - Design and synthesis of an artificial ladder-shaped polyether that interacts with
      glycophorin A.
AB  - Ladder-shaped polyether (LSP) compounds, such as brevetoxins and ciguatoxins, are
      thought to interact with transmembrane (TM) proteins. As a model LSP compound, we
      designed and synthesized an artificial tetracyclic ether (1) and evaluated its
      interaction with glycophorin A (GpA), a membrane protein known to dimerize or
      oligomerize between membrane-integral alpha-helical domains. Model compound 1 was
      found to induce the dissociation of oligomeric GpA in a similar manner to natural
      LSPs when examined by SDS-PAGE. The results suggest that even an artificial
      tetracyclic ether possesses the ability to interact with TM proteins, presumably
      through the intermolecular hydrogen bonds (C(alpha)-Hcdots, three dots,
      centeredO) with the GXXXG motif.

PMID- 16990000
TI  - Genotoxic activity of halogenated phenylglycine derivatives.
AB  - The discovery of genotoxic amino acids derived from phenylglycine, and possessing
      halogen substituents, is described. The utility of hypervalent iodine reagents in
      the synthesis of this class of compounds is highlighted. The mechanism of action
      of the (haloaryl)glycines was studied in Saccharomyces cerevisiae.

PMID- 16990001
TI  - Synthesis and biological evaluation of 5-arylamino-6-chloro-1H-indazole-4,7
      diones as inhibitors of protein kinase B/Akt.
AB  - A series of 5-arylamino-6-chloro-1H-indazole-4,7-diones were synthesized and
      evaluated for their inhibitory activity on protein kinase B/Akt. The compounds
      exhibited a potent Akt1 inhibitory activity. Further mechanistic study revealed
      that they might have dual inhibitory effects on both activity and phosphorylation
      of Akt1 in PC-3 tumor cell line.

PMID- 16990002
TI  - Development of 6-substituted indolylquinolinones as potent Chek1 kinase
      inhibitors.
AB  - Through a comparison of X-ray co-crystallographic data for 1 and 2 in the Chek1
      active site, it was hypothesized that the affinity of the indolylquinolinone
      series (2) for Chek1 kinase would be improved via C6 substitution into the
      hydrophobic region I (HI) pocket. An efficient route to 6-bromo-3-indolyl
      quinolinone (9) was developed, and this series was rapidly optimized for potency
      by modification at C6. A general trend was observed among these low nanomolar
      Chek1 inhibitors that compounds with multiple basic amines, or elevated polar
      surface area (PSA) exhibited poor cell potency. Minimization of these parameters
      (basic amines, PSA) resulted in Chek1 inhibitors with improved cell potency, and
      preliminary pharmacokinetic data are presented for several of these compounds.

PMID- 16990003
TI  - Synthesis, aerobic cytotoxicity, and radiosensitizing activity of novel 2,4
      dinitrophenylamine tethered 5-fluorouracil and hydroxyurea.
AB  - Two novel dual functional agents, 3[3-(2,4-dinitro-phenylamino)-propyl]-5-fluoro
      1H-pyrimidine-2,4-dione 7 and N-[3-(2,4-dinitro-phenylamino)-propoxy]urea 8,
      resulting from linkage of 2,4-dinitrophenylamine through three carbon atoms with
      5-fluorouracil 5 and hydroxyurea 6, respectively, were prepared and their in
      vitro aerobic cytotoxicities in HT-29 cell line with and without radiation were
      determined. Compounds 7 and 8 unlike their components were not cytotoxic but
      showed radiosensitizing activity.

PMID- 16990004
TI  - Synthesis of thiazolone-based sulfonamides as inhibitors of HCV NS5B polymerase.
AB  - Several thiazolone-based sulfonamides were prepared, utilizing various hetero
      aryl sulfonyl chlorides and different aldehydes, as inhibitors of NS5B
      polymerase, to target HCV. The best compound showed 0.6 microM [corrected] of
      IC50 inhibitory activity.

PMID- 16990005
TI  - Identification of 2-arylbenzimidazoles as potent human histamine H4 receptor
      ligands.
AB  - A series of 2-arylbenzimidazoles was synthesized and found to bind with high
      affinity to the human histamine H(4) receptor. Structure-activity relationships
      were investigated through library preparation and evaluation as well as
      traditional medicinal chemistry approaches, leading to the discovery of compounds
      with single-digit nanomolar affinity for the H(4) receptor.

PMID- 16990007
TI  - A history of scanning electron microscopy developments: towards "wet-STEM"
      imaging.
AB  - A recently developed imaging mode called "wet-STEM" and new developments in
      environmental scanning electron microscopy (ESEM) allows the observation of nano
      objects suspended in a liquid phase, with a few manometers resolution and a good
      signal to noise ratio. The idea behind this technique is simply to perform STEM
      in-SEM, that is SEM in transmission mode, in an environmental SEM. The purpose of
      the present contribution is to highlight the main advances that contributed to
      development of the wet-STEM technique. Although simple in principle, the wet-STEM
      imaging mode would have been limited before high brightness electron sources
      became available, and needed some progresses and improvements in ESEM. This new
      technique extends the scope of SEM as a high-resolution microscope, relatively
      cheap and widely available imaging tool, for a wider variety of samples.

PMID- 16990006
TI  - Synthesis and evaluation of a classical 2,4-diamino-5-substituted-furo[2,3
      d]pyrimidine and a 2-amino-4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine as
      antifolates.
AB  - Two classical antifolates, a 2,4-diamino-5-substituted furo[2,3-d]pyrimidine and
      a 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidine, were synthesized as
      potential inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase
      (TS). The syntheses were accomplished by condensation of 2,6-diamino-3(H)-4-oxo
      pyrimidine with alpha-chloro-ketone 21 to afford two key intermediates 23 and 24,
      followed by hydrolysis, coupling with l-glutamate diethyl ester and
      saponification of the diethyl ester to afford the classical antifolates 13 and
      14. Compounds 13 and 14 with a single carbon atom bridge are both substrates for
      folylpoly-gamma-glutamate synthetase (FPGS), the enzyme responsible for forming
      critical poly-gamma-glutamate antifolate metabolites with increased potency
      and/or increased cell retention. Compound 14 is a highly efficient FPGS substrate
      demonstrating that 2,4-diamino-5-substituted furo[2,3-d]pyrimidines are important
      lead structures for the design of antifolates with FPGS substrate activity. It
      retains inhibitory potency for DHFR and TS compared to the two atom bridged
      analog 5. Compound 13 is a poor inhibitor of purified DHFR and TS, and both 13
      and 14 are poor inhibitors of the growth of CCRF-CEM human leukemia cells in
      culture, indicating that single carbon bridged compounds in these series though
      conducive to FPGS substrate activity were not potent inhibitors.

PMID- 16990008
TI  - Olfactory bulbectomy in mice leads to increased BDNF levels and decreased
      serotonin turnover in depression-related brain areas.
AB  - The olfactory bulbectomy in rodents has been proposed as an animal model for
      depression. According to the neurotrophin and monoamine hypotheses of depression,
      the present study examined neurotrophin and monoamine (serotonin, norepinephrine,
      dopamine) levels in several depression-related brain regions of mice subjected to
      olfactory bulbectomy. As expected, bulbectomized animals revealed behavioral
      alterations such as locomotor hyperactivity and reduced gain of bodyweight,
      regarded as correlates of a depressive-like state. Compared to sham-operated
      animals, bulbectomized mice demonstrated significantly increased brain-derived
      neurotrophic factor (BDNF), but regular nerve growth factor (NGF), protein levels
      in hippocampus (+108%) and frontal cortex (+48%) 16 days after olfactory
      bulbectomy. In these brain regions as well as in the hypothalamus, bulbectomy
      also caused a reduction of the molar ratio of 5-hydroxyindoleacetic acid to
      serotonin (5-HT) indicating a decrease in 5-HT turnover. Similarly, a
      hypofunction of the dopamine (DA) turnover was evident only in the hypothalamus
      in response to olfactory bulbectomy, presenting a decrease in the ratio 3,4
      dihydroxyphenylacetic acid/DA with increased levels of DA. In all other brain
      areas investigated the levels of DA, its metabolite DOPAC and norepinephrine
      remained unaltered. Thus, olfactory bulbectomy seems to be a valid animal model
      also in mice related to serotonergic dysfunctions resembling bulbectomized rats
      that are a well-known model of hyposerotoninergic agitated depression. With
      respect to the common BDNF hypothesis of depression--predicting decreased BDNF
      expression in depression-related brain areas--the novel and challenging
      conclusions concern the increased BDNF protein levels in target regions of the
      cholinergic basal forebrain system in bulbectomized mice.

PMID- 16990009
TI  - Carbamazepine protects against megencephaly and abnormal expression of BDNF and
      Nogo signaling components in the mceph/mceph mouse.
AB  - Carbamazepine (CBZ) is a commonly used antiepileptic drug known to block voltage
      gated sodium channels. Infants exposed to CBZ in utero show reduced head
      circumference, for reasons unknown. We investigated CBZ's effect on neural growth
      in megencephaly (mceph/mceph) mice lacking functional Kv1.1. Mice fed with CBZ
      were assessed for brain structure size, seizure behavior and expression of
      markers for neuronal plasticity and rescue in brain. CBZ counteracted brain
      overgrowth and the increased size of neurons in the mceph/mceph mouse. These
      effects of CBZ occurred at doses that did not fully suppress epileptic behavior.
      Furthermore, CBZ normalized Bdnf mRNA levels and mRNA species encoding Nogo
      signaling pathway proteins. In conclusion, CBZ protects efficiently against
      abnormal growth and abnormal expression patterns of nerve growth signaling
      systems in the mceph/mceph brain. These observations and the effect of CBZ in
      utero suggest that CBZ treatment might be advantageous in some types of human
      idiopathic megalencephaly.

PMID- 16990010
TI  - Tumor suppressor Fhit protein interacts with protoporphyrin IX in vitro and
      enhances the response of HeLa cells to photodynamic therapy.
AB  - Fhit, the product of tumor suppressor fragile histidine triad (FHIT) gene,
      exhibits antitumor activity of still largely unknown cellular background.
      However, it is believed that Fhit-Ap(3)A or Fhit-AMP complex might act as a
      second class messenger in cellular signal transduction pathway involved in cell
      proliferation and apoptosis. We demonstrate here for the first time that the
      photosensitizer, protoporphyrin IX (which is a natural precursor of heme) binds
      to Fhit protein and its mutants in the active site in vitro. Furthermore, PpIX
      inhibits the enzymatic activity of Fhit. Simultaneously, PpIX shows lower binding
      capacity to mutant Fhit-H96N of highly reduced hydrolase activity. In cell-based
      assay PpIX induced HeLa cell death in Fhit and Fhit-H96N-dependent manner which
      was measured by means of MTT assay. Moreover, HeLa cells stably expressing Fhit
      or mutant Fhit-H96N were more susceptible to protoporphyrin IX-mediated
      photodynamic therapy (2J/cm(2)) than parental cells.

PMID- 16990011
TI  - A new, transportable ergometer for the measurement of musculotendinous stiffness
      during wrist flexion.
AB  - We present here a new, dedicated mechanical device for monitoring quick-release
      movements of the wrist. The ergometer was designed to easily assess
      musculotendinous properties during wrist flexion. Maximal voluntary contractions
      (MVC) and quick-release (QR) movements during wrist flexion were performed on 14
      subjects. A validation of the ergometer, using a test-retest methodology, was
      performed to assess its reliability and sensitivity. The device has been
      technically and biomechanically validated in a range of situations, including
      inertia measurement (mean inertia was found 0.0119+/-0.0012 N m s(2) rad(-1)) and
      appearance of the unloading reflex. Our results indicate that the device provides
      highly reliable, sensitive evaluation of wrist muscle stiffness (intraclass
      correlation coefficient for inertia, maximal voluntary contraction and stiffness
      index were 0.873, 0.994 and 0.930, respectively). Its portability facilitates
      measurement of the influence of repetitive, occupational activity on the
      musculotendinous complex of the wrist flexors.

PMID- 16990012
TI  - Effect of walking speed changes on tibialis anterior EMG during healthy gait for
      FES envelope design in drop foot correction.
AB  - Functional electrical stimulation may be used to correct hemiplegic drop foot. An
      optimised stimulation envelope to reproduce the EMG pattern observed in the
      tibialis anterior (TA) during healthy gait has been proposed by O'Keeffe et al.
      [O'Keeffe, D.T., Donnelly, A.E., Lyons, G.M., 2003. The development of a
      potential optimised stimulation intensity envelope for drop foot applications.
      IEEE Transactions on Neural Systems and Rehabilitation Engineering]. However this
      envelope did not attempt to account for changes in TA activity with walking
      speed. The objective of this paper was to provide data to enable the
      specification of an algorithm to control the adaptation of an envelope with
      walking speed. Ten young healthy subjects walked on a treadmill at 11 different
      walking speeds while TA EMG was recorded. The results showed that TA EMG recorded
      around initial contact and at toe off changed with walking speed. At the slowest
      velocities, equivalent to hemiplegic walking, the toe-off burst (TOB) of EMG
      activity had larger peak amplitude than that of the heel-strike burst (HSB). The
      peak amplitude ratio of TOB:HSB was 1:0.69 at the slowest speed compared to,
      1:1.18 and 1:1.5 for the self-selected and fastest speed, respectively. These
      results suggest that an FES envelope, which produces larger EMG amplitude for the
      TOB than the HSB, would be more appropriate at walking speeds typical of
      hemiplegic patients.

PMID- 16990014
TI  - Unconscious semantic priming in the absence of partial awareness.
AB  - In a recent paper in Psychological Science, Kouider and Dupoux reported obtaining
      unconscious Stroop priming only when subjects had partial awareness of the masked
      distractor words (i.e., could consciously perceive subword features that enabled
      reconstruction of whole words). Kouider and Dupoux conjectured that semantic
      priming occurs only when such partial awareness is present. The present
      experiments tested this conjecture in an affective categorization priming task
      that differed from Kouider and Dupoux's in using masked distractors that subjects
      had practiced earlier as visible words. Experiment 1 showed priming from
      practiced words when subjects had no partial awareness of those words. Experiment
      2 showed that, in the absence of partial awareness, practiced words yielded
      priming but not-practiced words did not. Experiment 3 corroborated Experiment 1
      and 2s results using a different test of partial awareness. These results suggest
      that unconscious processing (rather than partial awareness) of subword elements
      drives masked semantic priming by practiced words.

PMID- 16990013
TI  - Cycling exercise and the determination of electromechanical delay.
AB  - The main aim of the present paper was to address the validity of a methodology
      proposed in a previous paper [Li L, Baum BS. Electromechanical delay estimated by
      using electromyography during cycling at different pedaling frequencies. J
      Electromyogr Kinesiol 2004;14(6):647-52], aimed at determining the
      electromechanical delay from pedaling exercise performed at various cadences.
      Twelve trained subjects undertook pedaling bouts corresponding to combinations of
      cadences ranging from 50 to 100 RPM and power output from 37.5% to 75% of Pmax.
      As cadence increased, peak torque angle was found to shift forward in crank cycle
      (from 60-65 degrees at 50 RPM to 75-80 degrees at 100 RPM, depending on the power
      output level), while muscle bursts shifted backward in accordance with previous
      works. It is therefore suggested to take into account this peak torque angle lag
      to improve the methodology proposed by Li and Baum. The present results also
      evidenced that the central strategy, consisting in earlier muscle activation in
      crank cycle as cadence increases, is only partial. Neural strategy seems to be a
      trade-off between mechanical efficiency of muscular force output and
      coactivation.

PMID- 16990015
TI  - Contribution of the frontal lobe to externally and internally specified verbal
      responses: fMRI evidence.
AB  - It has been suggested that within the frontal cortex there is a lateral to medial
      shift in the control of action, with the lateral premotor area (PMA) involved in
      externally specified actions and the medial supplementary motor areas (SMA)
      involved in internally specified actions. Recent brain imaging studies
      demonstrate, however, that the control of externally and internally specified
      actions may involve more complex and overlapping networks involving not only the
      PMA and the SMA, but also the pre-SMA and the lateral prefrontal cortex (PFC).
      The aim of the present study was to determine whether these frontal regions are
      differentially involved in the production of verbal responses, when they are
      externally specified and when they are internally specified. Participants engaged
      in three overt speaking tasks in which the degree of response specification
      differed. The tasks involved reading aloud words (externally specified), or
      generating words aloud from narrow or broad semantic categories (internally
      specified). Using fMRI, the location and magnitude of the BOLD activity for these
      tasks was measured in a group of ten participants. Compared with rest, all tasks
      activated the primary motor area and the SMA-proper, reflecting their common role
      in speech production. The magnitude of the activity in the PFC (Brodmann area
      45), the left PMAv and the pre-SMA increased for word generation, suggesting that
      each of these three regions plays a role in internally specified action
      selection. This confirms previous reports concerning the participation of the pre
      SMA in verbal response selection. The pattern of activity in PMAv suggests
      participation in both externally and internally specified verbal actions.

PMID- 16990016
TI  - Phylogeny of betanodaviruses and molecular evolution of their RNA polymerase and
      coat proteins.
AB  - The betanodaviruses are the causative agent of the disease viral nervous necrosis
      in fishes. Betanodavirus genome consists of two single-stranded positive-sense
      RNA molecules (RNA1 and RNA2). RNA1 gene encodes the RNA polymerase, named also
      protein A, while RNA2 encodes the coat protein precursor, the CPp protein. We
      investigated the evolutionary relationships among betanodaviruses working on
      partial sequences of both RNA1 and RNA2. Phylogenetic analyses were performed by
      applying a maximum likelihood approach. The phylogenetic relationships among the
      major betanodavirus clades SJNNV-IV, TPNNV-III, BFNNV-II and RGNNV-I were
      resolved differently in the trees obtained, respectively, from RNA1 and RNA2
      multiple alignments. The alternative topologies were corroborated by strong
      bootstrap values. The molecular evolution of proteins A and CPp was also
      investigated. Protein A appeared to have evolved under strong purifying selection
      while the CPp protein was subject to both purifying and neutral selection in
      different amino acid residues. Intragenic recombination in RNA1 and RNA2 genes
      was investigated by applying several methods and was not detected. Conversely
      reassortment of RNA1 and RNA2 genes was demonstrated in some isolates. Finally
      RNA1 and RNA2 genes substitution rates do not follow a clock-like behavior thus
      impeding estimation of a possible origin time for Betanodavirus genus.

PMID- 16990017
TI  - Use of a murine cell line for identification of human nitric oxide synthase
      inhibitors.
AB  - INTRODUCTION: Nitric oxide (NO) has been implicated in a wide range of
      physiological and pathological processes. Low concentrations of this mediator
      play homeostatic roles, whereas many acute and chronic responses are associated
      with excessive production of NO. This upregulation is due in part to the
      induction of inducible nitric oxide synthase (iNOS) by proinflammatory cytokines
      in several different cell types, including macrophages and their CNS derivative,
      microglia. METHODS: The crystal structures of the oxygenase domains of mouse and
      human iNOS were superimposed using the "align by homology" feature in Sybyl
      (SYBYL 7.0, Tripos Inc.). NOS isoform expression was assessed by TaqMan, Western
      blotting, and activity assays. RESULTS: We demonstrate that there is a high
      degree of three-dimensional overlap between the mouse and human iNOS active
      centers and propose that the murine isoform can serve as a suitable substitute
      for the human in assays. We also demonstrate that LPS stimulation of the mouse
      macrophage cell line RAW 264.7 induces the expression of iNOS, but not nNOS or
      eNOS, at the levels of mRNA transcription and protein expression. Furthermore,
      the pharmacology and calcium dependency of the NO formation support the finding
      that it is due to iNOS alone. Also reported is the demonstration of LPS-induced
      RAW 264.7 macrophages in simple cell-based and cell-free screening assays for
      iNOS inhibitors. Both assays were reproducible, as demonstrated by Z' factors of
      0.69 and 0.71, and had high signal to noise ratios of 11- and 6-fold for the cell
      based and cell-free assay, respectively. DISCUSSION: Our computational analyses
      indicate that there is a high degree of three-dimensional overlap between the
      oxygenase domains of human and murine iNOS. This observation together with the
      selective induction of murine iNOS in RAW 264.7 macrophages demonstrates the
      potential utility of the mouse iNOS assay to identify inhibitors of the human
      enzyme.

PMID- 16990018
TI  - An integrated microdialysis rat model for multiple
      pharmacokinetic/pharmacodynamic investigations of serotonergic agents.
AB  - INTRODUCTION: Integrated in vivo models applying intracerebral microdialysis in
      conjunction with automated serial blood sampling in conscious, freely moving
      rodents are an attractive approach for pharmacokinetic (PK) and simultaneous
      pharmacokinetic/pharmacodynamic (PK/PD) investigations of CNS active drugs within
      the same animal. In this work, the ability to obtain and correlate data in this
      manner was evaluated for the selective serotonin (5-HT) reuptake inhibitor (SSRI)
      escitalopram. METHODS: An instrumented rat model equipped with an intracerebral
      hippocampal microdialysis probe and indwelling arterial and venous catheters was
      applied in the studies. Concomitant with brain microdialysis, serial blood
      sampling was conducted by means of an automated blood sampling device. The
      feasibility of the rat model for simultaneous PK/PD investigations was examined
      by monitoring plasma and brain extracellular concentrations of escitalopram along
      with SSRI-associated pharmacological activity, monitored as changes in brain 5-HT
      levels and plasma corticosterone levels. RESULTS: Combining intracerebral
      microdialysis and automated blood sampling did not cause any detectable
      physiological changes with respect to basal levels of plasma corticosterone or
      brain 5-HT levels. Furthermore, the PK of escitalopram in hippocampus following
      intravenous injection was not influenced by the presence of vascular catheters.
      Conversion of escitalopram dialysate concentrations into absolute extracellular
      levels by means of in vivo retrodialysis was verified by the no-net-flux method,
      which gave similar recovery estimates. The PK of escitalopram could be
      characterized simultaneously in plasma and the hippocampus of conscious, freely
      moving rats. Concomitantly, the modulatory and functional effects of escitalopram
      could be monitored as increases in brain 5-HT and plasma corticosterone levels
      following drug administration. DISCUSSION: The applicability of intracerebral
      microdialysis combined with arterial blood sampling was demonstrated for
      simultaneous PK/PD investigations of escitalopram in individual rats under non
      stressful conditions. Together, these temporal relationships provide multiple
      PK/PD information in individual animals, hence minimizing inter-animal variation
      using a reduced number of animals.

PMID- 16990019
TI  - The shape of the inferior part of the glenoid: a cadaveric study.
AB  - Previously, the shape of the inferior glenoid has been described as a circle with
      a bare spot being the center of that circle. This cadaveric study was done to
      test that statement. Forty cadaveric scapulae were used in this study. Two
      researchers used a digital image analysis program to assess the shape of the
      inferior glenoid and measured the distances from the bare spot to the anterior,
      inferior, and posterior cartilage and the bone rim. In 39 of 40 scapulae, the
      inferior glenoid had the shape of a true circle. Statistical analysis showed that
      the center of the bare spot is not the mathematical center of the inferior
      glenoid, but the differences in distances to the anterior, inferior, and
      posterior rims were very small (1.16-2.41 mm). Both observations can be used for
      further development of methods for measuring glenoid bone loss in patients with
      anterior glenohumeral instability.

PMID- 16990020
TI  - Expression of vascular endothelial growth factor and angiogenesis in the diabetic
      frozen shoulder.
AB  - The purpose of this study was to investigate neovascularization and the
      expression of vascular endothelial growth factor (VEGF) in patients with diabetic
      frozen shoulders. Eleven patients with diabetic frozen shoulders underwent
      arthroscopic lysis of adhesions, and we observed the reported findings. VEGF
      expression was determined by immunohistochemistry and Western blot analysis, and
      the density of vessels was evaluated based on CD34 immunoreactivity by use of
      samples of the synovial tissue. For the control group, we took 5 samples of
      synovium from patients undergoing shoulder arthroscopy. The arthroscopic findings
      showed hyperemia of the synovial tissue in all cases of diabetic frozen shoulder.
      This synovium showed stronger immunostaining to VEGF (P = .010) and CD34 (P =
      .011) than the control synovial tissue. Western blot analysis also showed a
      stronger VEGF intensity than in the control group. We postulate that VEGF is
      synthesized and secreted in the synovium of diabetic frozen shoulders and VEGF
      may have some role in the pathogenesis and neovascularization of frozen shoulders
      in diabetic patients.

PMID- 16990021
TI  - Glenoid bone grafting with a reverse design prosthesis.
AB  - The purpose of this study was to evaluate the outcome of patients who underwent
      glenoid bone grafting and implantation of a reverse design prosthesis in 1 or 2
      stages for the treatment of glenoid bone loss and rotator cuff insufficiency.
      Indications for the reverse prosthesis in this series included cuff tear
      arthropathy and revision arthroplasty. Nine patients were reviewed clinically and
      radiographically with a minimum 2-year follow-up (range, 24-41 months). Despite a
      low postoperative functional score (mean Constant score, 53 points [range, 22-79
      points]), most patients were satisfied with their results primarily because of
      pain relief. (The mean pain score increased from 3 points preoperatively to 12.5
      points postoperatively.) Radiographic evaluation did not demonstrate component
      loosening or evidence of graft failure. Six patients had radiographic evidence of
      an inferior scapular notch, which may be of concern in the future. Early results
      of this procedure are encouraging, but further clinical and radiologic assessment
      is necessary.

PMID- 16990022
TI  - Osseous anatomy of the distal humerus and proximal ulna: implications for total
      elbow arthroplasty.
AB  - Cortical thickness and multiple intramedullary canal diameters were measured in
      sequential axial sections from 27 human cadavers. No age or side differences were
      identified. The intramedullary humeral canal shape changed along the length of
      the bone in both male specimens and female specimens. Anteroposterior and male
      minimal humeral canal diameters increased proximally from the elbow. Male and
      female medial-lateral humeral diameters decreased proximally from the elbow. All
      ulnar canal diameters decreased distally in a uniform fashion. The minimal ulnar
      and humeral canal diameters did not occur in either the sagittal or coronal
      plane. Humeral and ulnar cortical thickness did not vary within axial sections.
      Only ulnar cortical thickness changed between sections, decreasing distally. On
      the basis of these data, a cylindrical humeral stem and an ulnar stem tapering in
      all planes may be optimal for total elbow arthroplasty stems. The relatively thin
      cortices of both the humerus and the ulna predispose patients to perforation,
      periarticular fracture, and complications during revision arthroplasty surgery.
      Finally, routine frontal and lateral radiographs may overestimate minimal canal
      size for total elbow arthroplasty components. However, the lateral view appears
      to approximate the true minimal canal diameter more closely.

PMID- 16990023
TI  - Articular cartilage injuries of the capitellum interposed in radial head
      fractures: a report of ten cases.
AB  - Ten cases of Mason type I and type II isolated radial head fractures are
      reported, in which an unexpected cartilaginous fragment of the capitellum trapped
      within the radial head fracture was identified at the time of surgery. In no case
      was this injury pattern identified on preoperative imaging, including computed
      tomography in 2 cases. Five patients did have preoperative mechanical findings
      with forearm rotation. At surgery, all capitellar fragments were found to
      originate from the posterolateral capitellum. Excision of the capitellar fragment
      and internal fixation of the radial head fracture were performed in all cases. No
      sequelae were identified on short-term follow-up. This series highlights an
      injury pattern that should be considered in isolated nondisplaced and minimally
      displaced fractures of the radial head. The natural history of this finding, when
      treated conservatively, is unknown.

PMID- 16990024
TI  - Biomechanical comparison of component position and hardware failure in the
      reverse shoulder prosthesis.
AB  - There has been renewed interest in reverse shoulder arthroplasty for the
      treatment of glenohumeral arthritis with concomitant rotator cuff deficiency.
      Failure of the prosthesis at the glenoid attachment site remains a concern. The
      purpose of this study was to examine glenoid component stability with regard to
      the angle of implantation. This investigation entailed a biomechanical analysis
      to evaluate forces and micromotion in glenoid components attached to 12
      polyurethane blocks at -15 degrees, 0 degrees, and +15 degrees of superior and
      inferior tilt. The 15 degrees inferior tilt had the most uniform compressive
      forces and the least amount of tensile forces and micromotion when compared with
      the 0 degrees and 15 degrees superiorly tilted baseplate. Our results suggest
      that implantation with an inferior tilt will reduce the incidence of mechanical
      failure of the glenoid component in a reverse shoulder prosthesis.

PMID- 16990025
TI  - Increased number of febrile seizures in children born very preterm: relation of
      neonatal, febrile and epileptic seizures and neurological dysfunction to seizure
      outcome at 16 years of age.
AB  - PURPOSE: In prematurely born population, a cascade of events from initial injury
      in the developing brain to morbidity may be followed. The aim of our study was to
      assess seizures in prematurely born children from birth up to 16 years and to
      evaluate the contribution of different seizures, and of neurological dysfunction
      to the seizure outcome. METHODS: Pre- and neonatal data and data from
      neurodevelopmental examination at 5 years of 60 prospectively followed children
      born at or before 32 weeks of gestation, and of 60 matched term controls from the
      2 year birth cohort were available from earlier phases of the study. Later
      seizure data were obtained from questionnaires at 5, 9, and 16 years, and from
      hospital records and parent interviews. RESULTS: In the preterm group, 16
      children (27%) exhibited neonatal seizures, 10 children (17%) had seizures during
      febrile illness and 5 children had epilepsy. Eight children had only febrile
      seizures, and 3 of these had both multiple simple and complex febrile seizures
      and neurodevelopmental dysfunction. None of the 8 children had experienced
      neonatal seizures, 6 had a positive family history of seizures, but none
      developed epilepsy. The children with epilepsy had CP and neurocognitive
      problems, and all but one had experienced neonatal seizures; two of them had also
      had fever-induced epileptic seizures. In controls 3 children (5%) had simple
      febrile seizures. CONCLUSION: Children born very preterm have increased rate of
      febrile seizures compared to the controls. However, no cascade from initial
      injury via febrile seizures to epilepsy could be shown during the follow-up of 16
      years. Symptomatic epilepsy in prematurely born children is characterised by
      neonatal seizures, major neurological disabilities and early onset of epilepsy.

PMID- 16990026
TI  - Hyal2, where are you?

PMID- 16990027
TI  - Disorders of acetabular labrum and articular cartilage in hip dysplasia:
      evaluation using isotropic high-resolutional CT arthrography with sequential
      radial reformation.
AB  - OBJECTIVE: Acetabular labral tear may predispose to adjacent articular cartilage
      disorder and hip osteoarthritis in patients with hip dysplasia. We evaluated the
      diagnostic ability of isotropic computed tomography (CT) arthrography with radial
      reformation technique for detection of acetabular labral and articular cartilage
      disorders, and evaluate those interactions in hip dysplasia. METHODS: Forty-one
      hips in 29 patients with hip dysplasia received CT arthrography with isotropic
      spatial resolution of 0.5mm. After processing of multiplanar radial reformation
      over the whole acetabular circumference, frequencies of labral tear and
      acetabular cartilage disorder were evaluated at six divided zones of the weight
      bearing areas. Of the 41 hips, 20 hips underwent arthroscopic examinations, and
      sensitivity, specificity and accuracy for detecting labral tear and acetabular
      cartilage disorder by CT arthrography were calculated using the arthroscopic
      findings as the standard of reference. RESULTS: The sensitivity, specificity and
      accuracy of CT arthrography were 97%/87%/92% for labral tear and 88%/82%/85% for
      acetabular cartilage disorder, respectively, using arthroscopic findings as the
      reference. The CT arthrography showed significantly higher frequency of labral
      and acetabular cartilage disorders at the anterior zones. Those zones with labral
      tear had significantly higher frequency of adjacent cartilage disorder than zones
      without labral tear. CONCLUSIONS: Isotropic CT arthrography with radial
      reformation technique allowed simultaneous, accurate assessment of labral and
      cartilage disorders in the whole acetabular circumference. Our findings indicated
      that labral tear is closely associated with adjacent cartilage disorder in hip
      dysplasia.

PMID- 16990028
TI  - Differences in trabecular structure between knees with and without osteoarthritis
      quantified by macro and standard radiography, respectively.
AB  - OBJECTIVE: To compare the sensitivity of standard and macro-radiography for
      quantifying cancellous bone differences between subjects with and without medial
      compartment knee osteoarthritis (OA). METHODS: Patients with medial compartment
      knee OA (n=24) and non-OA reference subjects (n=10) had a standard and a macro
      radiograph (x4 magnification) of one knee. Fractal Signature Analysis (FSA), a
      computerised image analysis technique, measured differences in cancellous bone
      structure between OA and non-OA tibiae in all radiographs. RESULTS: Compared to
      non-OA, FSA of vertical trabeculae in macro-radiographs increased significantly
      (P<0.05) in the OA group at several trabecular widths (0.30-0.60mm, 0.7 mm, 0.98
      1.14 mm) and in standard radiographs at a single trabecular width (0.48 mm).
      CONCLUSION: Compared to standard radiography, increased spatial resolution of
      macro-radiography allowed greater detection of trabecular bone differences
      between OA and non-OA knees. Nonetheless, difference was also detected in
      standard radiographs.

PMID- 16990029
TI  - Endothelin-1 combined with extracellular matrix proteins promotes the adhesion
      and chemotaxis of amelanotic melanocytes from human hair follicles in vitro.
AB  - During the repigmentation of vitiliginous skin, amelanotic melanocytes (AMMCs)
      migrate from the outer root sheath (ORS) of the hair follicles into depigmented
      skin. It has been shown that endothelin-1 (ET-1) is an important cytokine in the
      migration of epidermal melanocytes, produced by keratinocytes particularly after
      irradiation with ultraviolet B (UVB). To further examine the role of ET-1 on the
      migration of AMMCs, we investigated the effects of ET-1 to the adhesion and
      chemotaxis of human AMMCs combined with extracellular matrix proteins (ECMP) and
      observed the effects on the actin and tubulin cytoskeleton of AMMC by ET-1. Human
      AMMCs were treated with different concentrations of ET-1 (0.1-100 nM) to observe
      adhesion on culture dishes coated with fibronectin (FN), laminin (LN) and
      collagen IV (CIV). In addition, chemotaxis on FN, LN and CIV coated micropore
      filters, with various concentrations of ET-1 as attractants, was investigated
      using a Boyden chemotaxis chamber. Cellular microfilaments and microtubules were
      immunostained with Rhodamine labeled actin and FITC labeled beta-tubulin. The
      effects of ET-1 on cytoskeleton were observed with laser confocal microscopy. The
      study demonstrated that ET-1 increases human AMMCs adhesion on FN in a dose
      dependent manner, but minor increases are found on the coated surface with LN and
      CIV. ET-1 also induces chemotaxis of AMMCs on CIV, LN and FN in a dose-dependent
      manner. The greatest effect was seen with CIV. Minor chemotactic effects were
      observed with non-coated surfaces. A concentration of >or=10nM ET-1 induced an
      apparent increase in stress fibers underneath the cell membrane, but no effects
      were found on tubulin. ET-1 has various effects on the adhesion and chemotaxis of
      AMMCs on various ECMP, which could be partly due to a modulation and
      reorganization of the actin cytoskeleton.

PMID- 16990030
TI  - The pattern of glucocorticoid and estrogen receptors may explain differences in
      steroid dependency of intrauterine prostaglandin production at parturition in
      sheep.
AB  - BACKGROUND: We have recently described two distinct pathways of intrauterine
      prostaglandin (PG) synthesis: a cortisol-dependent/estradiol-independent
      mechanism within trophoblast tissue leading to elevations in fetal plasma PGE2,
      and an estradiol-dependent mechanism within maternal endometrium that leads to
      increased maternal plasma PGF2(2alpha). We hypothesized that the differential
      effects of cortisol and estradiol on intrauterine PGH synthase-II (PGHS-II)
      expression and PG production may be because of the tissue specific expression of
      the glucocorticoid and estradiol receptors (GR and ER, respectively) within the
      intrauterine tissues. In addition, we suggest that these two pathways of PG
      production are linked through the expression of P450(C17hydroxylase) (P450(C17))
      and subsequent increase in placental estradiol synthesis. METHODS: To test the
      hypotheses, we infused singleton, chronically catheterized fetal sheep beginning
      at day 125 of gestation (term 147 to 150 days) with (1) cortisol (0.45 mg/mL; n =
      5); (2) cortisol and 4-hydroxyandrostenedione, a P450(aromatase) inhibitor (4
      OHA: 1.44 mg/h; n = 5); (3) saline (n = 5); or (4) saline and 4-OHA (n = 5). PGHS
      II, ER alpha, ER beta, and GR alpha were localized using immunohistochemistry. ER
      alpha, ER beta, P450(C17), and GR alpha protein expressions were determined by
      Western blot analysis. Data were analyzed by analysis of variance (ANOVA) (P < or
      =.05). RESULTS: Fetal cortisol infusion in the presence or absence of a rise in
      placental estrogen synthesis increased placental expression of GR alpha; both
      PGHS-II and GR alpha localized to the uninucleate trophoblast cells of the
      placentome and were excluded from the maternal stroma and binucleate cells. Both
      forms of ER were excluded from the trophoblast tissue of the placentome. ER
      alpha, ER beta, and PGHS-II showed a similar pattern of distribution within the
      luminal epithelium of the endometrium; there were no alterations in the level of
      the ER in the presence of cortisol +/- 4-OHA. Placental P450(C17) protein
      expression was increased in the presence of a rise in fetal cortisol independent
      of changes in placental estrogen synthesis. CONCLUSIONS: We concluded that the
      differential effects of cortisol and estradiol on intrauterine PGHS-II expression
      and PG production may be due to the tissue-specific expression of the GR and ER
      within the intrauterine tissues. Glucocorticoid effects on trophoblast PG
      production may be mediated in a positive feed-forward manner. We further suggest
      that either cortisol or a cortisol-stimulated intermediate, like PGE2, increased
      P450(C17) expression, leading to a rise in placental estradiol synthesis and
      triggering maternal intrauterine tissue PG production.

PMID- 16990031
TI  - The role of endometrium in endometriosis.
AB  - Endometriosis is defined as the presence of endometrial glands and stroma outside
      the uterus. Several theories have been proposed to explain the pathogenesis of
      this disease. According to Sampson's retrograde menstruation theory, endometrial
      cells are refluxed through the fallopian tubes during the menstruation and
      implant onto peritoneum or pelvic organs. Since retrograde menstruation is a very
      common phenomenon among women of reproductive age, there must be other factors
      that may contribute to the pathophysiology and/or pathogenesis of endometriosis.
      Genetic predisposition, environmental factors, and alterations in immune and
      endocrine functions are believed to play significant roles in the establishment
      and maintenance of endometriosis. Although the eutopic endometriums of women with
      and without endometriosis are histologically similar, studies revealed that there
      are many fundamental differences between these two tissues. Invasive properties,
      decreased apoptosis, alterations in expression of specific gene and proteins, and
      increased steroid and cytokine production have been identified in eutopic
      endometrium of women with endometriosis. Furthermore, significant biochemical
      differences exist even between ectopic and autologous eutopic endometrium. These
      differences can be explained by the direct effects of an inflammatory peritoneal
      environment.

PMID- 16990032
TI  - Oxidant/antioxidant status of placenta, blood, and cord blood samples from
      pregnant women supplemented with iron.
AB  - OBJECTIVE: In this study, it was aimed to investigate oxidant/antioxidant status
      in placenta and in blood and cord blood samples from pregnant women supplemented
      with iron during pregnancy. METHODS: For this purpose, 27 pregnant women at
      admission for delivery participated in the study. Fifteen of them did not take
      iron tablets and the others took oral iron supplements during pregnancy.
      Following delivery, part of the placenta and blood and cord blood samples were
      taken from the mothers. In these samples, oxidant parameters (malondialdehyde
      [MDA] levels and xanthine oxidase [XO] activities) and antioxidant parameters
      (antioxidant potential [AOP] values, superoxide dismutase [SOD], catalase [CAT]
      and glutathione peroxidase [GSH-Px] activities) were studied. RESULTS: It was
      found that MDA level and SOD activities increased significantly in the placentas
      from the iron-supplemented group as compared with those from the control group.
      We also observed that activities of SOD and XO enzymes in maternal erythrocytes,
      XO in cord blood erythrocytes and GSH-Px activities in cord blood plasma
      decreased significantly. However, activities of CAT and GSH-Px enzymes in cord
      blood erythrocytes and MDA levels in maternal plasma increased in the iron
      supplemented group as compared with those from the control group. CONCLUSION:
      Increased MDA levels in the maternal plasma and the placenta in the iron
      supplemented group suggests that iron supplementation may contribute to increased
      oxidative stress in women taking iron supplements during pregnancy.

PMID- 16990033
TI  - Estrogen receptor-beta is the predominant estrogen receptor subtype in normal
      human synovia.
AB  - OBJECTIVE: Joint pain increases after menopause with more than 50% of woman
      suffering from arthralgies. Since pain and inflammation of joints originate from
      synovial tissue, we aimed to discover whether estrogen receptors are present in
      the human synovia. METHODS: This in vitro study was performed on samples of human
      synovial tissue, obtained from pre- (n = 8) and postmenopausal woman (n = 11) and
      men (n = 5) following surgery due to traumatic lesions. Fresh synovial tissue
      specimens were assessed for the localization as well as the presence of estrogen
      receptor-alpha (ER alpha) and estrogen receptor-beta (ER beta) by means of
      immunohistochemistry, as well as Western blot and reverse transcriptase
      polymerase chain reaction (RT-PCR), respectively. RESULTS: ER beta protein and
      mRNA were found to be equally and highly expressed in synovial stroma and lining
      cells of all explants independent of sex or menopausal status. In contrast, weak
      ER alpha staining was localized in the synovial lining cells in only three of 24
      explants. ER alpha protein was found to be weakly expressed in three of ten
      explants. ER alpha mRNA was found with highly variable amounts in seven of ten
      explants. CONCLUSION: In view of our observation that ER beta but not ER alpha is
      expressed regularly in normal human synovia in high amounts, we propose that
      estrogen could play a significant role in synovial membrane function in women and
      men, operating preferably via the ER beta isoform.

PMID- 16990034
TI  - Matrix metalloproteinase-1 and -9 promoter polymorphisms and endometrial
      carcinoma risk in a Japanese population.
AB  - OBJECTIVE: The matrix metalloproteinases (MMPs) are a family of zinc-dependent
      proteases that degrade all the components of the extracellular matrix (ECM).
      Several studies have demonstrated association between MMP gene polymorphisms and
      various cancers. The object of this study was to investigate whether the MMP-1
      and MMP-9 gene promoter polymorphisms are associated with endometrial carcinomas
      in a Japanese population. METHODS: We compared the allele frequencies and
      genotype distributions of each single nucleotide polymorphism in the promoter
      regions of MMP-1 (-1607 1G/2G) and MMP-9 (-1562 C/T) in 107 endometrial carcinoma
      cases and 213 controls using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) analysis. RESULTS: The allele frequencies of MMP-1
      -1607 2G and MMP-9 -1562T were 64.0% and 10.7% in the cases and 70.0% and 16.7%
      in the controls, respectively. No significant differences in the allele
      frequencies or genotype distributions were found between cases and controls for
      the MMP-1 -1607 1G/2G polymorphism. However, a small but significant difference
      in the allele frequency of the MMP-9 -1562T allele was noted between cases and
      controls (P = .046; odds ratio [OR] = 1.01; 95% confidence interval [CI], 1.01 to
      2.73). Stratification by histology revealed a significant difference in the
      frequency of the MMP-9 -1562T allele between endometrioid carcinoma cases (10.2%)
      and controls (P = .043; OR = 1.76; 95% CI, 1.02 to 3.03); we did not find a
      significant difference in the frequency of the MMP-9 -1562T allele between non
      endometrioid carcinoma cases (13.2%) and controls. CONCLUSION: These results
      suggest that the MMP-9 -1562 C/T polymorphism may be associated with
      susceptibility to endometrioid carcinoma in the Japanese population.

PMID- 16990035
TI  - Landmark-based but not vestibular-based orientation elicits mossy fiber
      synaptogenesis in the mouse hippocampus.
AB  - This study tries to shed light on the paradoxical finding that two inbred strains
      of mice C57BL/6 (C57) and DBA/2 (DBA), with differences in hippocampal function,
      perform similarly in the water maze (WM). Mice from both strains were trained on
      WM protocols permitting or preventing the use of vestibular signals. Hippocampal
      involvement in performance was then assessed by estimation of post-training mossy
      fiber (MF) synaptogenesis. We found that C57 and DBA mice performed similarly
      when both visual and vestibular information were available but only C57 mice
      exhibited new MF synapses. Disruption of vestibular inputs impaired performance
      in DBA mice but not in C57 mice which still exhibited a post-training increase of
      hippocampal MF synaptic terminals. This strain-specific dissociation indicates
      that DBA mice can navigate successfully by relying on vestibular signals without
      engaging their hippocampus. In contrast, vestibular signals are irrelevant for
      C57 mice since their suppression neither disrupts their behavior nor prevents the
      formation of new hippocampal synapses. These findings suggest some caution is
      required in considering performance on standard WM protocols as an index of
      hippocampus-based learning. Estimating the extent of post-training mossy fiber
      synaptogenesis would be helpful in solving this issue.

PMID- 16990036
TI  - Functional characterization of the Aspergillus fumigatus calcineurin.
AB  - Aspergillus fumigatus is an aggressive opportunistic pathogen of humans as well
      as a major allergen. Environmental sensing and retrieving essential nutrients
      from the environment are general metabolic traits associated with the growth of
      this saprophytic fungus. Two important mediators of calcium signals in eukaryotic
      cells are the Ca(2+)-binding protein calmodulin and the Ca(2+)/calmodulin
      dependent phosphatase calcineurin. Calcineurin is a heterodimer that consists of
      a catalytic subunit A and a Ca(2+)/calmodulin binding unit. We deleted the A.
      fumigatus calA gene, which encodes the calcineurin A catalytic subunit, and
      demonstrated that this gene is not essential in this fungus. The DeltacalA mutant
      strain has severe defects in growth extension, branching and conidial
      architecture. Furthermore, the A. fumigatus DeltacalA mutant strain has decreased
      fitness in a low dose murine infection and cannot grow in fetal bovine serum
      (FBS). After potassium phosphate was added to liquid FBS, the DeltacalA mutant
      strain could grow with the characteristic phenotype of the DeltacalA mutation.
      When A. fumigatus calcineurin is inhibited by tacrolimus in a phosphate depleted
      medium, there is a reduction in the inorganic phosphate transport and six
      putative phosphate transporter genes have altered mRNA levels. However, there is
      no effect on the acid phosphatase activity. These results suggest that
      calcineurin is involved in the regulation of the PHO pathway in A. fumigatus. Our
      work on calcineurin opens new venues for the research on sensing and nutrient
      acquisition in A. fumigatus.

PMID- 16990037
TI  - Multidrug-resistant endosymbiotic bacteria account for the emergence of
      zygomycosis: A hypothesis.
AB  - Although the extensive use of Aspergillus-active antifungals has been recently
      associated with an increase in zygomycosis in several cancer centers, the
      frequency of this opportunistic mycosis began to rise earlier, since the mid
      1990s. The reasons for that emergence are unclear. Recent evidence suggests that
      endosymbiotic bacteria of Rhizopus species produce toxins that enhance fungal
      pathogenicity. We postulate that, although Zygomycetes appear equally ubiquitous
      and virulent to Aspergillus, zygomycosis was rare in the past in immunosuppressed
      patients specifically because of the widespread use of antibacterials in this
      patient population. Such use may have resulted in inhibition of endosymbiotic,
      toxin-producing bacteria and led indirectly in attenuation of Zygomycetes
      virulence. Thus, the growing rates of antimicrobial resistance over the past
      decade selected for multidrug-resistant endosymbiotic bacteria of Zygomycetes,
      which could facilitate the emergence of zygomycosis. This hypothesis, if true,
      will be the first paradigm of modulation of virulence of opportunistic fungi by
      antibacterials.

PMID- 16990038
TI  - Identification of OS-2 MAP kinase-dependent genes induced in response to osmotic
      stress, antifungal agent fludioxonil, and heat shock in Neurospora crassa.
AB  - Two-component signal transduction comprising of OS-1 (histidine kinase), OS-4
      (MAPKK kinase), OS-5 (MAPK kinase), and OS-2 (MAP kinase) plays an important role
      in osmotic regulation in Neurospora crassa. To identify the genes regulated
      downstream of OS-2 MAP kinase, quantitative real-time RT-PCR analysis was
      conducted in selected genes based on Hog1 MAP kinase regulated genes in yeast. In
      response to osmotic stress and fludioxonil, expression of six genes that for
      glycerol synthesis (gcy-1, gcy-3, and dak-1), gluconeogenesis (fbp-1 and pck-1),
      and catalase (ctt-1) was activated in the wild-type strain, but not in the os-2
      mutant. A heat shock treatment also induced their expression in the same way.
      Consisting with the gene expression, the enzyme activity of glycerol
      dehydrogenase, but not glycerol-3-phosphate dehydrogenase, was increased in
      response to osmotic stress and fludioxonil in the wild-type strain. OS-2 was
      phosphorylated by the OS-1 cascade in response to relatively low osmotic stress
      and fludioxonil. However, OS-2 phosphorylation by heat shock and a higher osmotic
      stress was found in the os-1 mutant normally but not in the os-4 and os-5
      mutants. These results suggested that non-OS-1 signaling activates OS-2 in an OS
      4-dependent manner in such conditions.

PMID- 16990039
TI  - Characterisation and phylogeny of repeated elements giving rise to exceptional
      length of ITS2 in several downy mildew genera (Peronosporaceae).
AB  - In downy mildews with pyriform haustoria (DMPH), ITS lengths between 1121 and
      2587kb were observed. The extreme length of ITS is due to sequence repeats of a
      poorly conserved part of the ITS2. Secondary structure analysis suggests that
      individual repeats may form long hairpin structures. The presence of these types
      of sequence repeats appears to be a synapomorphy for the DMPH. In another group
      of downy mildews, represented by Hyaloperonospora, similar REs sporadically
      occur, although with element lengths that are shorter than those in the DMPH
      group. Two characteristic motifs could be identified and their role in the
      evolution of the REs is briefly discussed. Dotplot analysis and molecular
      phylogenetic reconstructions for the repeated elements of representative species
      show distinct patterns that may suggest how they evolved. The high amount of
      sequence variability makes the repeated units a useful tool to study speciation
      and radiation processes in an economically important group of plant pathogens,
      which may form a model system for studying other coevolutionary host-pathogen
      systems.

PMID- 16990040
TI  - How do obligate parasites evolve? A multi-gene phylogenetic analysis of downy
      mildews.
AB  - Plant parasitism has independently evolved as a nutrition strategy in both true
      fungi and Oomycetes (stramenopiles). A large number of species within
      phytopathogenic Oomycetes, the so-called downy mildews, are defined as obligate
      biotrophs since they have not, to date, been cultured on any artificial medium.
      Other genera like Phytophthora and Pythium can in general be cultured on standard
      or non-standard agar media. Within all three groups there are many important
      plant pathogens responsible for severe economic losses as well as damage to
      natural ecosystems. Although they are important model systems to elucidate the
      evolution of obligate parasites, the phylogenetic relationships between these
      genera have not been clearly resolved. Based on the most comprehensive sampling
      of downy mildew genera to date and a representative sample of Phytophthora
      subgroups, we inferred the phylogenetic relationships from a multi-gene dataset
      containing both coding and non-coding nuclear and mitochondrial loci.
      Phylogenetic analyses were conducted under several optimality criteria and the
      results were largely consistent between all the methods applied. Strong support
      is achieved for monophyly of a clade comprising both the genus Phytophthora and
      the obligate biotrophic species. The facultatively parasitic genus Phytophthora
      is shown to be at least partly paraphyletic. Monophyly of a cluster nested within
      Phytophthora containing all obligate parasites is strongly supported. Within the
      obligate biotrophic downy mildews, four morphologically or ecologically well
      defined subgroups receive statistical support: (1) A cluster containing all
      species with brownish-violet conidiosporangia, i.e., the genera Peronospora and
      Pseudoperonospora; (2) a clade comprising the genera with vesicular to pyriform
      haustoria (Basidiophora, Benua, Bremia, Paraperonospora, Plasmopara, Plasmoverna,
      Protobremia); (3) a group containing species included in Hyaloperonospora and
      Perofascia which almost exclusively infect Brassicaceae; (4) a clade including
      the grass parasites Viennotia oplismeni and Graminivora graminicola. Phylogenetic
      relationships between these four clades are not clearly resolved, and neither is
      the position of Sclerospora graminicola within the downy mildews. Character
      analysis indicates an evolutionary scenario of gradually increasing adaptation to
      plant parasitism in Peronosporales and that at least the most important of these
      adaptive steps occurred only once, including major host shifts within downy
      mildews.

PMID- 16990041
TI  - Interactions between cell surface protein disulphide isomerase and S
      nitrosoglutathione during nitric oxide delivery.
AB  - In this study, we investigated the role of protein disulphide isomerase (PDI) in
      rapid metabolism of S-nitrosoglutathione (GSNO) and S-nitrosoalbumin (albSNO) and
      in NO delivery from these compounds into cells. Incubation of GSNO or albSNO (1
      microM) with the megakaryocyte cell line MEG-01 resulted in a cell-mediated
      removal of each compound which was inhibited by blocking cell surface thiols with
      5,5'-dithiobis 2-nitrobenzoic acid (DTNB) (100 microM) or inhibiting PDI with
      bacitracin (5mM). GSNO, but not albSNO, rapidly inhibited platelet aggregation
      and stimulated cyclic GMP (cGMP) accumulation (used as a measure of intracellular
      NO entry). cGMP accumulation in response to GSNO (1 microM) was inhibited by MEG
      01 treatment with bacitracin or DTNB, suggesting a role for PDI and surface
      thiols in NO delivery. PDI activity was present in MEG-01 conditioned medium, and
      was inhibited by high concentrations of GSNO (500 microM). A number of cell
      surface thiol-containing proteins were labelled using the impermeable thiol
      specific probe 3-(N-maleimido-propionyl) biocytin (MPB). Pretreatment of cells
      with GSNO resulted in a loss of thiol reactivity on some but not all proteins,
      suggesting selective cell surface thiol modification. Immunoprecipitation
      experiments showed that GSNO caused a concentration-dependent loss of thiol
      reactivity of PDI. Our data indicate that PDI is involved in both rapid
      metabolism of GSNO and intracellular NO delivery and that during this process PDI
      is itself altered by thiol modification. In contrast, the relevance of PDI
      mediated albSNO metabolism to NO signalling is uncertain.

PMID- 16990042
TI  - Amino-acid selective experiments on uniformly 13C and 15N labeled proteins by MAS
      NMR: Filtering of lysines and arginines.
AB  - Amino-acid selective magic-angle spinning (MAS) NMR experiments can aid the
      assignment of ambiguous cross-peaks in crowded spectra of solid proteins. In
      particular for larger proteins, data analysis can be hindered by severe resonance
      overlap. In such cases, filtering techniques may provide a good alternative to
      site-specific spin-labeling to obtain unambiguous assignments that can serve as
      starting points in the assignment procedure. In this paper we present a simple
      pulse sequence that allows selective excitation of arginine and lysine residues.
      To achieve this, we make use of a combination of specific cross-polarization for
      selective excitation [M. Baldus, A.T. Petkova, J. Herzfeld, R.G. Griffin, Cross
      polarization in the tilted frame: assignment and spectral simplification in
      heteronuclear spin systems, Mol. Phys. 95 (1998) 1197-1207.] and spin diffusion
      for transfer along the amino-acid side-chain. The selectivity of the filter is
      demonstrated with the excitation of lysine and arginine side-chain resonances in
      a uniformly 13C and 15N labeled protein preparation of the alpha-spectrin SH3
      domain. It is shown that the filter can be applied as a building block in a 13C
      13C lysine-only correlation experiment.

PMID- 16990043
TI  - Identification and characterisation of an 8.7 kb deletion and a novel nonsense
      mutation in two Italian families with Sanfilippo syndrome type D
      (mucopolysaccharidosis IIID).
AB  - Sanfilippo syndrome type D is an autosomal recessive lysosomal storage disease
      that is caused by a deficiency of N-acetylglucosamine-6-sulphatase, one of the
      enzymes involved in the catabolism of heparan sulphate. Only 15 patients have
      been described in the literature and just two mutations have been reported to
      date. We present the clinical, biochemical and molecular analysis of two Italian
      Sanfilippo D families. Novel homozygous mutations were identified in the affected
      patients from each family: a large intragenic deletion of 8723 bp encompassing
      exons 2 and 3 in family 1 and a nonsense mutation, Q272X, in family 2. The
      deletion is the first large intragenic deletion to be reported in any of the four
      Sanfilippo subtypes, including Sanfilippo type C in which the gene has recently
      been identified.

PMID- 16990044
TI  - The incidence of pneumonia in rural Thailand.
AB  - BACKGROUND: Pneumonia continues to be a leading infectious disease killer, yet
      accurately measuring incidence remains a challenge. In 2002, Thailand began
      active, population-based surveillance for radiographically confirmed pneumonia in
      Sa Kaeo Province. METHODS: Full-time surveillance officers conducted active case
      ascertainment at every hospital, and routine audits and a community cluster
      survey promoted complete and accurate reporting. A case of pneumonia was defined
      as acute infection with signs or symptoms of lower respiratory tract infection
      and evidence of new infiltrates. An independent panel of radiologists reviewed
      digital images of all radiographs. RESULTS: Between September 2002 and August
      2003, 777 patients met the case definition. The measured minimum incidence was
      177/100,000 but the estimated incidence was as high as 580/100,000 with full
      adjustment for incomplete chest radiography and access to health care. Seventy
      two (9%) patients died and 28% were known to be HIV positive. Fifteen (2%)
      patients had pneumonia twice during the year. The average cost of hospitalization
      for an episode of pneumonia ranged from US$490.80 to $628.60. CONCLUSIONS:
      Pneumonia is a significant and costly public health problem in Thailand. This
      surveillance system allows precise assessment and monitoring of radiologically
      confirmed pneumonia and lays the groundwork for the introduction of new vaccines
      against pneumonia pathogens.

PMID- 16990045
TI  - Genetic toxicity testing of 3-methyl-2H-furo[2,3-c]pyran-2-one, an important
      biologically active compound from plant-derived smoke.
AB  - Aerosol smoke, aqueous smoke solutions and 3-methyl-2H-furo[2,3-c]pyran-2-one
      isolated from plant-derived smoke stimulate seed germination and enhance seedling
      vigour of many species. Consequently, smoke technology has important potential
      applications in agriculture, horticulture and other environmental sectors.
      However, use of 3-methyl-2H-furo[2,3-c]pyran-2-one as a germination promoter
      and/or growth stimulant is only possible provided it can be shown that it is not
      hazardous, i.e. not toxic or genotoxic. We therefore performed an investigation
      to evaluate the genotoxic effects of this compound in five strains of Salmonella
      typhimurium in the Ames test (1.5microg/plate to 7.5ng/plate), and in the VITOTOX
      test (1500-0.045ppb). In all tests performed, no mutagenic activity was induced
      by 3-methyl-2H-furo[2,3-c]pyran-2-one, with or without S9 metabolic activation.
      Due to the potential wide use of this smoke-derived compound, it is of importance
      that no toxic and genotoxic effects were observed at the concentrations tested.

PMID- 16990046
TI  - Microbubble-induced increase in ablation of liver tumors by high-intensity
      focused ultrasound.
AB  - We studied the possibility of using high-intensity focused ultrasound (HIFU)
      together with a microbubble agent to treat hepatocellular carcinoma. Development
      of liver tumors in rats was induced by administration of Dimethylnitrosamin
      (100ppm). Rats with liver tumors were anesthetized, underwent laparotomy, and
      were given the microbubble agent Levovist or saline intravenously. After the
      injection, the liver was exposed to HIFU for 30s (2.18MHz, 600W/cm(2), 40mm in
      diameter). Immediately after HIFU exposure, ultrasound images of the HIFU area
      were evaluated. Then the liver was excised and the volume of coagulated tissue
      was measured. The mean volumes of hyperechoic areas after HIFU were as follows
      (mm(3), Levovist versus saline: 355.3+/-180.7 versus 47.4+/-35.6, P<0.001, n=13).
      The volumes of liver tissue coagulated by HIFU were as follows (mm(3), Levovist
      versus saline: 275.3+/-120.0 versus 60.1+/-23.6, P<0.001, n=13). On microscopic
      examination of areas exposed to HIFU, implosion cysts were seen, and many cancer
      cells were found to have been destroyed completely (loss of cell membranes or
      nuclei). In conclusion, the microbubble agent Levovist can increase the volume of
      tissue coagulated by HIFU.

PMID- 16990047
TI  - AAV1-LPL(S447X) gene therapy reduces hypertriglyceridemia in apoE2 knock in mice.
AB  - Intramuscular (IM) application of adeno-associated virus serotype 1 (AAV1) for
      the delivery of human lipoprotein lipase (hLPL) was previously shown efficacious
      in mice with chylomicronemia. The current study addresses whether AAV1-LPL(S447X)
      can reduce elevated triglyceride (TG) levels in mice with attenuated clearance of
      TG-rich remnant particles. METHODS: Female mice, expressing human apoE2 but
      deficient for endogenous apoE (apoE2KI) received IM injections of AAV1-LPL(S447X)
      (n=6; 8 x 10(12) gc/kg; 4-sites) or PBS (n=5). Following lipid monitoring, the
      mice were challenged with intravenous Intralipid injections, and sacrificed 3
      months after treatment. RESULTS: In the mice that received LPL gene therapy, a
      marked increase of post-heparin hLPL protein levels (averaging 517+/-277 ng/mL
      vs. 4+/-3 ng/mL in apoE2KI-untreated) induced 20% reductions of fasting plasma TG
      levels (p<0.05). This was accompanied by two-fold increased TG clearance rates
      after Intralipid administration at 6 weeks after treatment (p<0.05). Post-mortem
      analyses revealed increased levels of TG (2-fold, p<0.005) and cholesterol (1.7
      fold, p<0.001) in the treated muscles. CONCLUSIONS: IM application of AAV1
      LPL(S447X) is effective in reducing TG levels in a mouse model for type III
      dyslipidemia. Thus, hypertriglyceridemia caused by attenuated uptake of TG-rich
      lipoproteins can be alleviated by increasing lipolytic function of the skeletal
      muscle tissue.

PMID- 16990048
TI  - Studies on the efficacy of Chloramine T trihydrate (N-chloro-p-toluene
      sulfonamide) against planktonic and sessile populations of different Legionella
      pneumophila strains.
AB  - Effectiveness of Chloramine T trihydrate (N-chloro-p-toluene sulfonamide) on both
      planktonic and sessile populations of different Legionella pneumophila strains
      was assessed. Although Chloramine T is a recommended commercial formulation for
      disinfecting cooling towers, there is a lack of published data about the efficacy
      of this compound against both planktonic and sessile populations of L.
      pneumophila. Planktonic L. pneumophila strains were suspended in tap water and
      sessile L. pneumophila strains were grown on stainless steel which is used in the
      construction of cooling towers, followed by exposure to the biocide. The
      sensitivity of both planktonic and sessile populations of L. pneumophila strains
      was different. The biocide was found effective below recommended dosages (0.1
      0.3%) against planktonic populations of L. pneumophila, whereas it was determined
      that higher dosages than those recommended were required for sessile populations
      of L. pneumophila. The results indicated that studying only the planktonic
      populations of L. pneumophila for biocide tests might not be sufficient to
      provide information about the optimum dosage and contact time. Therefore,
      efficacy has to be tested on both planktonic and sessile bacteria.

PMID- 16990049
TI  - Importance of the gut-brain axis in the control of glucose homeostasis.
AB  - Adult mammals finely match glucose production to glucose utilization, thus
      allowing glycaemia to be maintained in a physiological range of 0.8-1.2mg/dl
      whatever the energetic status of the mammal (i.e. fed or fasted, rested or
      exercised). To accomplish this, peripheral signals originating from the gut
      'inform' the central nervous system, which in turn is able to monitor the status
      of both peripheral glucose stores and ongoing fuel availability. Indeed, both
      secretion and action of hormones regulating endogenous glucose production and
      utilization are regulated by the autonomic nervous system. These gut signals are
      either hormonal (e.g. glucagon-like peptide-1, ghrelin and cholecystokinine) or
      neuronal (e.g. afferent vagus nerve fibres). Recent data, combined with the
      development of incretin analogues for treatment of diabetes, highlight the
      importance of the gut-brain axis, especially glucagon-like peptide-1 and ghrelin,
      in the control of glucose homeostasis.

PMID- 16990050
TI  - Altered susceptibility to EAE in congenic NOD mice: Altered processing of the
      encephalitogenic MOG35-55 peptide by NOR/LtJ mice.
AB  - NOD mice (H-2 g7) naturally develop autoimmune diabetes, while the congenic
      NOR/LtJ mice (H-2 g7) are resistant. To determine if defective immune regulation
      renders NOD susceptible to autoimmune disease, we compared MOG35-55-induced EAE
      in NOD mice to that of NOR/LtJ. In two of three immunization protocols, the
      NOR/LtJ mice developed significantly reduced indices and severity of clinical
      disease, in spite of an exaggerated autoimmune response to MOG35-55.
      Characterization of the responding T cell repertoires revealed that V beta 8+ Th
      cells directed toward the MOG42-55 core epitope were dominant in both strains.
      Interestingly, CD8+ CTL were absent or significantly reduced in MOG35-55
      lymphoblasts from NOR/LtJ mice, which poorly processed the MOG39-47 CTL epitope
      from MOG35-55. Thus, while particular MHC class II alleles may be associated with
      increased risk, molecules involved in the processing of key epitopes may be
      influential in the progression of autoimmune disease.

PMID- 16990051
TI  - Re-shaping the T cell repertoire: TCR editing and TCR revision for good and for
      bad.
AB  - Protection against the universe of pathogens requires a functional, diverse T
      cell repertoire. However, the price that is paid for an evolved, effective immune
      system includes the potential danger of generating autoaggressive T cells.
      Autoimmune diseases result from inherent breach of tolerance to self-antigens
      leading to disruption of the regulatory to autoaggressive T cell homeostatic
      balance. The immune system has evolved mechanisms to control those processes. For
      T cells, positive and negative selection in the thymus assures that only fully
      functional, non-self-reactive T cells will populate the periphery. Failure of
      this central tolerance would result in autoaggressive T cells escaping into the
      periphery. However, other means of escaping negative selection can occur in the
      periphery, i.e., TCR revision, or the altering of TCR expression after thymic
      egress. Here the potential benefits, i.e., expansion and re-shaping of the T cell
      repertoire as potentiated by TCR editing and revision are considered.
      Furthermore, the potential to develop autoaggressive TCR and thus enhance
      autoimmunity is considered.

PMID- 16990052
TI  - Valproic acid, a histone deacetylase inhibitor, is an antagonist for oncolytic
      adenoviral gene therapy.
AB  - Oncolytic adenoviruses preferentially replicate in and lyse tumor cells. However,
      their application to cancer gene therapy has been complicated by the low levels
      of coxsackie and adenovirus receptor (CAR) expressed in many solid tumors.
      Histone deacetylase inhibitors (HDACIs) significantly up-regulate CAR expression
      in tumor cells and have additional antineoplastic activities. Therefore, there is
      a clear rationale for the combination of HDACIs and oncolytic adenoviral gene
      therapy. We present evidence that HDACI treatment significantly inhibits
      adenoviral replication, viral burst, and tumor cell kill. Valproic acid (VPA), a
      well-established HDACI, inhibits adenoviral replication late in the viral life
      cycle. We hypothesized that VPA induction of the cell-cycle-regulating protein
      p21(WAF1/CIP1) may be partly responsible for this activity. We demonstrate that
      p21(WAF1/CIP1) expression alone limits viral replication and decreases viral
      titers in different cancer cell models. We also demonstrate that VPA and
      replicating adenovirus mutually inhibit each other's ability to kill cells,
      independent of p21(WAF1/CIP1) expression. These results not only identify the
      importance of p21(WAF1/CIP1) in the biology of adenoviral replication, but also
      suggest that oncolytic adenoviral gene therapy will be inhibited rather than
      enhanced by VPA (HDACI) treatment.

PMID- 16990053
TI  - Circadian rhythm abnormalities in the acute phase of cerebral infarction
      correlate with poor prognosis in the chronic phase.
AB  - The aim of this study was to determine circadian rhythm abnormalities in patients
      with acute cerebral infarction and their relationship with prognosis in the
      chronic phase. The subjects were 50 patients who were admitted within 48 h of
      onset. Rectal temperature and wrist motor activity were recorded during the acute
      phase. Time-series data were assayed by MEM spectral analysis. Functional
      prognosis (degree of handicap) was assessed at 3 months after stroke onset by the
      modified Rankin Scale. Ambulatory patients tended to exhibit circadian rhythm in
      rectal temperature and/or wrist activity rhythms, whereas non-ambulatory patients
      did not (P < 0.001) in the acute phase of ischemic stroke. Our findings suggest
      the biological rhythms of rectal temperature and wrist activity during the acute
      stroke phase might be a possible prognostic indicator of their chronic phase.

PMID- 16990054
TI  - Genetic analysis of ionizing radiation-induced mutagenesis in Saccharomyces
      cerevisiae reveals TransLesion Synthesis (TLS) independent of PCNA K164
      SUMOylation and ubiquitination.
AB  - Ionizing radiation-induced mutagenesis (IR-IM) underlies a basis for radiation
      associated carcinogenesis as well as resistance to radiation therapy. This
      process was examined in Saccharomyces cerevisiae using an array of isogenic DNA
      repair deficient mutants. Mutations inactivating homologous recombination (rad51,
      52, 54) or nucleotide excision repair (rad1, rad10, rad4) caused elevated IR-IM
      whereas inactivation of TransLesion Synthesis (TLS: rad6) caused severely
      defective IR-IM. Of the mutations inactivating TLS polymerases, rev3 and rev1
      caused equally severe defects in IR-IM whereas rad30 did not significantly affect
      the process. The effects of the rev3, rev1, and rad6 mutations on IR-IM were
      epistatic, suggesting the requirement of both polymerase zeta and Rev1p in IR-IM
      related TLS. Although PCNA K164 SUMOylation/ubiquitination is a proposed
      prerequisite for TLS, the IR-IM defect of a rev3 or a rad6 mutant was worse than
      and epistatic to the pol30K164R mutant, a mutant in which the PCNA had been
      mutated to abolish such modifications. These results suggested that IR-IM related
      TLS occurs in the absence of PCNA K164 modification. Further analysis of a mutant
      simultaneously defective in SUMOylation and mono-ubiquitination (rad18 siz1)
      revealed that these modifications redundantly affected TLS as well as NHEJ. A
      genetic model based on these observations is proposed.

PMID- 16990055
TI  - Use of a double balloon enteroscope facilitates caecal intubation after
      incomplete colonoscopy with a standard colonoscope.
AB  - BACKGROUND: Caecal intubation is a necessary step in the complete endoscopic
      evaluation of the colon. Studies have estimated that experienced colonoscopists
      may fail to reach the caecum in up to 10% of cases. AIMS: To evaluate the utility
      of the double balloon enteroscope used for complete examination of the colon in
      patients with incomplete standard colonoscopy. PATIENTS: Twenty consecutive
      patients with incomplete colonoscopies within the Veterans Affairs Palo Alto
      Health Care System. Mean age of 66 years (S.D.+/-12 years, range 46-84), 16 men.
      METHODS: Prospective single-centre case series on the caecal intubation rate
      using standard double balloon enteroscope technique in patients with previous
      incomplete conventional colonoscopy. RESULTS: Use of the standard double balloon
      enteroscope technique permitted complete colonoscopy to be achieved in 95% of the
      patients (19/20). Seven patients (35%) had significant pathology beyond the
      extent of the prior incomplete colonoscopy. We performed endoscopic mucosal
      resection, polypectomy or biopsy. The mean time to reach the caecum was 28 min
      (S.D.+/-20 min, range 6-90 min). The sedation was similar to conventional
      colonoscopy. No complications occurred. CONCLUSIONS: The double balloon
      enteroscope technology and technique can be used to complete examination of the
      colon in patients who were referred because of incomplete standard colonoscopy.

PMID- 16990056
TI  - Fat embolism and IM nailing.

PMID- 16990057
TI  - Fat embolism: special situations bilateral femoral fractures and pathologic
      femoral fractures.
AB  - Few data are available in the literature regarding fat embolism in cases of
      bilateral femoral and pathological femoral fractures. The incidence of bilateral
      femoral fractures ranges from 2-9.5% of the total number of patients with femoral
      fractures, and they usually occur in high energy trauma and multi-trauma
      patients. Although injury severity scores tend to underestimate the severity of
      these injuries, fat embolism seems to occur in increased frequency ranging from
      4.8-7.5%. Intramedullary nailing, which is the preferred surgical treatment,
      triggers a systemic inflammatory response that poses an additional burden to
      pulmonary function. In addition, the femur is a common site of metastatic bone
      disease. The treatment of impending and actual pathological fractures is
      complicated by increased rates of lung damage due to various factors. Fat
      embolism during treatment--mainly with intramedullary nails--generally seems to
      range from 0-10%.

PMID- 16990058
TI  - Experimental background--review of animal studies.
AB  - Most of the research on the physiological effects of intramedullary nailing is
      technically difficult or ethically impossible to perform in humans. A substantial
      range of factors apply in clinical cases, which means that the data obtained from
      this source may lack the control needed to reveal the basic mechanisms of
      pathophysiology associated with this surgical procedure. Consequently, animal
      studies have been relied upon to provide answers that would otherwise be
      unavailable. This review manuscript summarizes the available literature on animal
      studies dealing with the local and systemic effects of intramedullary nailing. It
      focuses on whether these studies have contributed to our clinical knowledge of
      the procedure's impact on perfusion and fracture healing, as well as the medical
      relevance of coincident systemic effects. DATA SOURCES: Medline, personal library
      of the first author and of the Department of Trauma Surgery, University of
      Pittsburgh Medical Center. STUDY SELECTION: All animal studies on intramedullary
      stabilization published in English, German, and French. CONCLUSIONS: The
      relevance of animal studies investigating the impact of a surgical procedure and
      its influence on concomitant injuries depends on the design and the type of the
      animal model. If this fact is considered, and if a model is selected that
      simulates a systemic impact comparable with the clinical situation, then animal
      studies may provide a valuable source of otherwise unobtainable information. Such
      an example is the study of fat embolization associated with intramedullary
      nailing. Animal subjects enable assessment of the intervention's additive
      surgical impact, measurement of side effects that may have adverse results, and
      influence of cofactors (eg, thoracic trauma, severe shock, polytrauma) that
      predispose the individual to postoperative complications.

PMID- 16990059
TI  - Fat embolism syndrome: history, definition, epidemiology.
AB  - The first clinical case of fat embolism was described over 100 years ago and
      significant progress has been made in the understanding of this condition since
      then. Gurd's criteria, consisting of major and minor clinical features, is the
      most commonly used diagnostic tool in the literature. Due to the lack of a gold
      standard for diagnosis, clinical criteria cannot be validated. It is now
      recognized that although fat embolization occurs in the majority of patients with
      long bone fractures, clinical signs and symptoms occur only in 1-10% of patients
      with fractures.

PMID- 16990060
TI  - Physical and technical aspects of intramedullary reaming.
AB  - Intramedullary pressure during reaming is influenced by various factors,
      including those of the patient, such as bone morphology and location and type of
      fracture, and those related to reaming technique and instruments. Through
      intensive research, technical developments and the use of modern materials,
      intramedullary pressure caused by modern reaming systems can be reduced to a
      minimum and, perhaps, completely avoided through use of the reaming-irrigation
      aspiration system.

PMID- 16990061
TI  - Fat embolism: the reaming controversy.
AB  - Intramedullary nailing is the preferred treatment method for stabilizing femoral
      diaphyseal fractures. Despite its superior biomechanical advantages over other
      implants, its use, particularly in selected groups of patients, has been
      questioned because of the possible harmful systemic effects of intramedullary
      reaming. The increase in intramedullary canal pressure during intramedullary
      nailing can result in intravasation of bone marrow and fat into the venous blood
      system. The subsequent consequences can be fat embolism syndrome (FES), adult
      respiratory distress syndrome (ARDS), and multiple organ failure. The lung seems
      to be the primary target for fat embolization and for the mediated effects primed
      by inflammatory reactions. In laboratory studies, both reamed and unreamed
      intramedullary nailing has been shown to alter selected pulmonary variables.
      Although transient, this effect appears to be more prominent with reamed than
      unreamed techniques. Additional studies are required to determine whether a
      subgroup of trauma patients is adversely affected by intramedullary reaming, thus
      necessitating other fixation techniques.

PMID- 16990062
TI  - Prevention of fat embolism syndrome.
AB  - Fat embolism syndrome is a condition of acute respiratory distress following long
      bone trauma. This condition may involve not only the lungs but also a number of
      other body systems. The pathophysiology is not as yet clearly understood,
      however, intravasation of fat from long-bone fractures may play a role. Early
      recognition of the severity of injury both on clinical and biochemical grounds
      and early surgical stabilization of long bones may help to decrease its
      incidence. However, the best surgical technique with which to do this
      stabilization has not yet been clearly determined. Surgical and pharmacological
      techniques have been developed in an attempt to either decrease the intravasation
      of fat during long-bone stabilization or block the inflammatory cascade with
      varying degrees of efficacy. Ongoing research focuses on both the prevention and
      treatment of this condition.

PMID- 16990063
TI  - Therapeutic aspects of fat embolism syndrome.
AB  - Signs and symptoms of clinical fat embolism syndrome (FES) usually begin within
      24-48 hours after trauma. The classic triad involves pulmonary changes, cerebral
      dysfunction, and petechial rash. Clinical diagnosis is key because laboratory and
      radiographic diagnosis is not specific and can be inconsistent. The duration of
      FES is difficult to predict because it is often subclinical or may be
      overshadowed by other illnesses or injuries. Medical care is prophylactic or
      supportive, including early fixation and general ICU management to ensure
      adequate oxygenation and ventilation, hemodynamic stability, prophylaxis of deep
      venous thrombosis, stress-related gastrointestinal bleeding, and nutrition.
      Studies support early fracture fixation as a method to reduce recurrent fat
      embolism and FES. The main therapeutic interventions once FES has been clinically
      diagnosed are directed towards support of pulmonary and neurological
      manifestations and management of acute lung injury (ALI) and acute respiratory
      distress syndrome (ARDS).

PMID- 16990064
TI  - Bone marrow fat in the circulation: clinical entities and pathophysiological
      mechanisms.
AB  - Fat embolism (FE) and fat embolism syndrome (FES) are controversial topics,
      particularly regarding their clinical relevance and their independency as a
      clinical syndrome. FE describes the presence of fat globules within the
      microcirculation. FES on the other hand, is a clinical syndrome characterized by
      the presence of FE with the manifestation of an identifiable clinical pattern of
      signs and symptoms. Both experimental and clinical studies have demonstrated the
      occurrence and the possible harmful effects of FE. For instance, FE involving the
      lungs can result in adult respiratory distress syndrome (ARDS). The effects of FE
      are certainly mechanical, leading to capillary congestion, but are also highly
      likely to be of a proinflammatory and prothrombotic nature. The demarcation of
      FES against ARDS is mainly demonstrated by the single organ involvement of ARDS,
      exclusively influencing the lungs, whereas FES has a multiorgan effect with
      pulmonary, skin and, neurological manifestations. This article is a review of the
      pathophysiological mechanisms of FE and the clinical occurrence and influence of
      FE and FES.

PMID- 16990066
TI  - A clinical investigation of the fit of removable partial dental prosthesis clasp
      assemblies.

PMID- 16990067
TI  - Prosthodontic treatment of a patient with hemimandibular elongation: a clinical
      report.
AB  - This clinical report describes prosthodontic treatment of a patient with
      hemimandibular elongation that resulted in significant dentofacial asymmetry. A
      maxillary metal-ceramic fixed dental prosthesis and crowns were fabricated. To
      eliminate the negative horizontal overlap, 3 mandibular teeth were reduced to the
      gingival level. The mandibular prosthetic restoration was completed with metal
      and composite resin using an electroforming technique.

PMID- 16990068
TI  - In vitro evaluation of low-temperature aging effects and finishing procedures on
      the flexural strength and structural stability of Y-TZP dental ceramics.
AB  - STATEMENT OF PROBLEM: Yttria-stabilized tetragonal zirconia polycrystal (Y-TZP)
      ceramic material has been reported to possess exceptionally high flexural
      strength; however, the strength of Y-TZP ceramics can be affected by surface
      treatments performed by dental laboratory technicians and by intraoral
      conditions. PURPOSE: This study investigated the influence of low-temperature
      degradation (LTD) treatment, airborne-particle abrasion, and polishing on the
      flexural strength and structural stability of a Y-TZP ceramic material. MATERIAL
      AND METHODS: By sectioning zirconia ceramic blocks (Vita In-Ceram YZ blocks) into
      25 x 4 x 2-mm bars, 310 specimens were fabricated and divided into 9 groups:
      Group C, as-sintered (control); group B24h, boiled in water for 24 hours; group
      B7d, boiled in water for 7 days; group H6h, stored in humidified air at 250
      degrees C for 6 hours; group H24h, stored in humidified air at 250 degrees C for
      24 hours; group H7d, stored in humidified air at 250 degrees C for 7 days; group
      P, polished; group A, airborne-particle abraded; and group AB, airborne-particle
      abraded and boiled for 7 days. The flexural strengths (MPa) of all specimens were
      determined by using a 3-point bending test. The variability was analyzed by using
      Weibull statistics. Pairwise differences among the 9 groups were evaluated by
      using confidence intervals (95%) for scale and shape parameters. From every block
      used, 8 specimens were obtained and every specimen was marked according to the
      location of its origin from the original block. Surfaces of the specimens were
      evaluated by using scanning electron microscopy (SEM) at various magnifications.
      X-ray diffraction analysis was performed to identify possible tetragonal-to
      monoclinic phase transformations. Energy dispersive spectroscopy (EDS) was used
      to obtain information on the chemical composition. RESULTS: Aging or "finishing"
      treatments had no significant negative effects on flexural strengths. Mean
      flexural strengths ranged from 796.7 to 950.2 MPa. Group A exhibited the highest
      mean flexural strength (950.2 MPa). Weibull modulus values ranged between 5.6 and
      9.3. Tetragonal-to-monoclinic phase transformation was detected for a specimen
      boiled for 24 hours. More tetragonal-to-monoclinic phase transformation was
      detected for specimens boiled for 7 days and stored in humidified air at 250
      degrees C for 7 days. The SEM examination of fractured surfaces revealed
      sintering defects, and EDS analysis showed less yttria concentration on Y-TZP
      specimens that were boiled for 7 days. CONCLUSION: Within the limitations of this
      study, the results suggested that the LTD procedures and the polishing treatment
      used did not reduce the flexural strengths of zirconia bars. Airborne-particle
      abrasion increased the flexural strength of specimens. CLINICAL IMPLICATIONS:
      Although polishing, airborne-particle abrasion, and various low-temperature
      degradation (LTD) treatments did not significantly degrade the strength of the Y
      TZP ceramic material, LTD resulted in loss of yttria. Over time, gradual
      dissolution of yttria could decrease the tetragonal-phase stability and long-term
      clinical serviceability of this dental ceramic material.

PMID- 16990069
TI  - Shear bond strength of metal-ceramic repair systems.
AB  - STATEMENT OF PROBLEM: When clinical fractures of the ceramic veneer on metal
      ceramic prostheses can be repaired, the need for remake may be eliminated or
      postponed. Many different ceramic repair materials are available, and bond
      strength data are necessary for predicting the success of a given repair system.
      PURPOSE: This study evaluated the shear bond strength of different repair systems
      for metal-ceramic restorations applied on metal and porcelain. MATERIAL AND
      METHODS: Fifty cylindrical specimens (9 x 3 mm) were fabricated in a nickel
      chromium alloy (Vera Bond II) and 50 in feldspathic porcelain (Noritake). Metal
      (M) and porcelain (P) specimens were embedded in a polyvinyl chloride (PVC) ring
      and received 1 of the following bonding and resin composite repair systems
      (n=10): Clearfil SE Bond/Clearfil AP-X (CL), Bistite II DC/Palfique (BT), CoJet
      Sand/Z100 (CJ), Scotchbond Multipurpose Plus/Z100 (SB) (control group), or CoJet
      Sand plus Scotchbond Multipurpose Plus/Z100 (CJSB). The specimens were stored in
      distilled water for 24 hours at 37 degrees C, thermal cycled (1000 cycles at 5
      degrees C to 55 degrees C), and stored at 37 degrees C for 8 days. Shear bond
      tests between the metal or ceramic specimens and repair systems were performed in
      a mechanical testing machine with a crosshead speed of 0.5 mm/min. Mean shear
      bond strength values (MPa) were submitted to 1-way ANOVA and Tukey honestly
      significant difference tests (alpha=.05). Each specimen was examined under a
      stereoscopic lens with x30 magnification, and mode of failure was classified as
      adhesive, cohesive, or a combination. RESULTS: On metal, the mean shear bond
      strength values for the groups were as follows: MCL, 18.40 +/- 2.88(b); MBT, 8.57
      +/- 1.00(d); MCJ, 25.24 +/- 3.46(a); MSB, 16.26 +/- 3.09(bc); and MCJSB, 13.11 +/
      1.24(c). On porcelain, the mean shear bond strength values of each group were as
      follows: PCL, 16.91 +/- 2.22(b); PBT, 18.04 +/- 3.23(ab); PCJ, 19.54 +/-
      3.77(ab); PSB, 21.05 +/- 3.22(a); and PCJSB, 16.18 +/- 1.71(b). Within each
      substrate, identical superscript letters denote no significant differences among
      groups. CONCLUSIONS: The bond strength for the metal substrate was significantly
      higher using the CJ system. For porcelain, SB, CJ, and BT systems showed the
      highest shear bond strength values, and only SB was significantly different
      compared to CL and CJSB (P<.05). CLINICAL IMPLICATIONS: This study suggests that
      when fracture involves only feldspathic porcelain, any of the evaluated systems
      may be used, since the fracture occurred on the porcelain substrate and not on
      the bond interface of porcelain-restorative material. However, for the nickel
      chromium alloy tested, the CoJet Sand system showed the best results for repair.

PMID- 16990070
TI  - Annual review of selected dental literature: report of the Committee on
      Scientific Investigation of the American Academy of Restorative Dentistry.

PMID- 16990071
TI  - Comparison of the occlusal vertical dimension after processing complete dentures
      made with lingualized balanced occlusion and conventional balanced occlusion.
AB  - STATEMENT OF PROBLEM: An increase in occlusal vertical dimension (OVD) may occur
      after processing complete dentures. Although many factors that generate this
      change are known, no information is available in the dental literature regarding
      the effect that the occlusal scheme may have on the change in OVD. PURPOSE: This
      in vitro study compared the increase in OVD, after processing, between complete
      dentures with teeth arranged in lingualized balanced occlusion and conventional
      balanced occlusion. MATERIAL AND METHODS: Thirty sets of complete dentures were
      evaluated as follows: 15 sets of complete dentures were arranged in conventional
      balanced occlusion (control) and 15 sets of complete dentures were arranged in
      lingualized balanced occlusion. All dentures were compression molded with a long
      polymerization cycle. The occlusal vertical dimension was measured with a
      micrometer (mm) before and after processing each set of dentures. Data were
      analyzed using an independent t test (alpha=.05). RESULTS: The mean increase in
      the OVD, after processing, was 0.87 +/- 0.21 mm for the control group and 0.90 +/
      0.27 mm for the experimental group. There was no significant difference between
      the groups. CONCLUSION: After processing, dentures set in lingualized balanced
      occlusion showed an increase in OVD similar to those set in conventional balanced
      occlusion. CLINICAL IMPLICATIONS: Although the 2 occlusal concepts resulted in
      similar increases in the OVD after processing, the lingualized balanced occlusion
      may result in easier occlusal adjustments, as the less complicated occlusal
      scheme uses a smaller number of centric occlusion contact points.

PMID- 16990072
TI  - Influence of acrylic resin polymerization methods and saliva on the adherence of
      four Candida species.
AB  - STATEMENT OF PROBLEM: There is limited information on the role of polymerization
      methods and saliva on the adherence of pathogenic Candida species, with the
      exception of the adherence of Candida albicans to acrylic resins and the relation
      of this to surface roughness and surface free energy, which appear to play a
      major role in the initial phases of microorganism adhesion. PURPOSE: This study
      evaluated the influence of polymerization methods and human whole saliva on the
      adherence of Candida species to acrylic resin surfaces. MATERIAL AND METHODS:
      Acrylic resin specimens (n=256) measuring 2.5 x 1.2 x 0.2 cm were heat (Classico)
      or microwave (OndaCryl) polymerized and evaluated for surface roughness using a
      profilometer, and for surface free energy by measuring the contact angle of a
      sessile drop of water. For the adherence assay, specimens of each acrylic resin
      were divided by lottery into 8 groups, according to whether they were exposed to
      human saliva or not (control), and to 1 of the 4 following suspensions: C
      albicans, Candida tropicalis, Candida dubliniensis, or Candida glabrata (1 to 5 x
      10(6) cells/mL). Adhered yeasts were counted using an optical microscope at x400
      magnification. Data were analyzed by 3-way ANOVA and the Tukey honestly
      significant difference test (alpha=.05). RESULTS: No statistical difference was
      found for roughness (P=.156), whereas higher surface free-energy values were
      found for the heat-polymerized acrylic resin (P=.0013). The overall adherence of
      Candida species was significantly decreased by human saliva (P<.001). CONCLUSION:
      Within the limitations of this study, saliva was capable of reducing the
      adherence of Candida species, whereas roughness and free energy did not influence
      the adherence rates. CLINICAL IMPLICATIONS: As growth on surfaces is a natural
      part of the Candida lifestyle, its colonization in denture users may be expected.
      The presence of human whole saliva, however, decreased the overall yeast
      adherence to the acrylic resin surface, whereas surface roughness and free energy
      did not interfere with the adherence of Candida species.

PMID- 16990073
TI  - Restoration of immediately placed implants in 3 appointments: from surgical
      placement to definitive prostheses.
AB  - This article describes a comprehensive approach that enables the clinician to
      place dental implants, and fabricate a provisional prosthesis and a definitive
      metal-acrylic resin or metal-ceramic fixed complete denture in 3 appointments.
      This technique allows the practitioner to immediately load the implants with a
      provisional fixed complete denture at the time of implant placement, to record
      the relative positions of the implants and soft tissues, the occlusal vertical
      dimension, maxillomandibular relationship, and tooth position at the second
      appointment by using the information provided by the provisional fixed denture,
      and to insert the definitive prosthesis at the third appointment. This technique
      reduces chair time for both the patient and the clinician, and could ultimately
      reduce the cost of implant treatment and potentially increase treatment
      acceptance.

PMID- 16990074
TI  - A method for avoiding demarcation lines when processing dentures with a
      definitive denture base.

PMID- 16990075
TI  - A simple open-tray implant impression technique.

PMID- 16990076
TI  - A technique to transfer screw-retained angled abutments before inserting a
      definitive prosthesis.

PMID- 16990077
TI  - Mild cognitive impairment: an opportunity to identify patients at high risk for
      progression to Alzheimer's disease.
AB  - BACKGROUND: There is increasing evidence that subtle losses in cognitive function
      may be symptomatic of a transition to early Alzheimer's disease (AD). Ongoing
      research is focusing on the identification of those individuals with mild
      cognitive impairment (MCI) who are most likely to convert to AD. Of the MCI
      subtypes, patients with amnestic MCI (a-MCI) are at greatest risk. OBJECTIVES:
      The objectives of this article were to review the relationship between MCI,
      normal aging, and AD, and to summarize recent research on the diagnosis and
      potential treatment of MCI. METHODS: Relevant articles were identified through
      searches of MEDLINE and EMBASE using the terms mild cognitive impairment;
      cognitive impairment, no dementia; and dementia prodrome, with no restrictions as
      to year. Additional papers of interest were identified from the reference lists
      of the identified articles. The search was current as of February 2006. RESULTS:
      Guidelines and recommendations are being developed to assist physicians in
      diagnosing MCI, identifying its subtype and etiology, understanding the risks for
      conversion to AD, and managing disease progression. Given the existence of a
      subset of individuals with a-MCI, who are at greatest risk for progression to AD
      but still have high levels of cognition and function, the ability to improve
      symptoms and delay progression to AD would be particularly beneficial. In a 3
      year, randomized, double-blind, placebo-controlled study in 769 patients with a
      MCI, treatment with the cholinesterase inhibitor donepezil was associated with a
      significantly lower rate of progression to AD compared with placebo during the
      first 12 months of treatment (hazard ratio=0.42; 95% CI, 0.24-0.76; P=0.004) but
      not at later time points. Of other types of agents that have been investigated
      (antioxidants, estrogen replacement therapy, cyclooxygenase-2-selective
      inhibitors), none have shown significant beneficial effects in delaying cognitive
      decline or progression to AD. New drugs such as secretase inhibitors, small
      molecules that disrupt amyloid aggregation, and immunotherapies are in
      preclinical development. CONCLUSIONS: MCI involves more substantial cognitive and
      memory decline than normal aging and represents a significant risk factor for the
      development of dementia. Further research is needed into treatments to delay the
      conversion from MCI to AD.

PMID- 16990078
TI  - Efficacy and tolerability of topiramate 200 mg/d in the prevention of migraine
      with/without aura in adults: a randomized, placebo-controlled, double-blind, 12
      week pilot study.
AB  - BACKGROUND: Several large, randomized, double-blind, placebo-controlled trials
      have found topiramate (TPM) to be effective and generally well tolerated as a
      preventive therapy for migraine. OBJECTIVE: This paper evaluates efficacy and
      safety data from a pilot study of TPM 200 mg/d as preventive therapy in adult
      subjects with a history of migraine with or without aura. METHODS: The pilot
      study had a randomized, double-blind, placebo-controlled design. Subjects were
      randomized in a 2:1 ratio to receive TPM 200 mg/d or placebo. The double-blind
      treatment phase consisted of an 8-week titration period (25 mg/d for the first
      week, followed by weekly increases of 25 mg) and a 12-week maintenance period.
      The primary efficacy measure was the change in mean monthly migraine frequency.
      Additional measures were the median percent reduction in monthly migraine
      frequency and the proportion of responders (those with > or =50%, > or =75%, or
      100% reduction in monthly migraine frequency). RESULTS: The intent-to-treat (ITT)
      population included 211 subjects (138 TPM, 73 placebo; mean [SD] mean weight,
      76.7 [18.7] kg). Of 45 subjects who discontinued the study in the TPM group, 21
      discontinued during the titration period, compared with 3 of 13 subjects who
      discontinued in the placebo group. When the efficacy data were assessed using the
      per-protocol, analysis-of-covariance model, TPM 200 mg/d was not associated with
      a significant reduction in mean monthly migraine frequency compared with placebo.
      A post hoc analysis using a Poisson regression model in the ITT population
      suggested that TPM significantly reduced mean monthly migraine frequency compared
      with placebo (P=0.04). A significantly larger proportion of TPM-treated subjects
      had a > or =75% reduction in monthly migraine frequency compared with placebo
      (P=0.03). At least 1 adverse event was reported by 90.0% and 69.9% of the TPM and
      placebo groups, respectively. Treatment-emergent adverse events (AEs) occurring
      in > or =10% of subjects in the TPM group were paresthesia (45%), dizziness
      (16%), fatigue (16%), nausea (14%), and weight loss (14%). Most treatment
      emergent AEs were rated mild or moderate in severity. Of 3 serious AEs
      (depression, abdominal pain, leg pain) occurring during the trial, none were
      considered related to either TPM or placebo. CONCLUSION: In this pilot study,
      mean monthly migraine frequency did not differ significantly between TPM and
      placebo.

PMID- 16990079
TI  - The effect of 6 months of treatment with pravastatin on serum adiponection
      concentrations in Japanese patients with coronary artery disease and
      hypercholesterolemia: a pilot study.
AB  - BACKGROUND: Pravastatin has been reported to reduce cardiovascular events and
      mortality in patients with coronary artery disease (CAD). Hypoadiponectinemia is
      a known risk factor for CAD. OBJECTIVE: This study analyzed the effects of
      shortterm pravastatin treatment on serum lipid and adiponectin concentrations in
      patients with CAD and hypercholesterolemia. METHODS: This was a multicenter,
      observational pilot study of the effect of 6 months of treatment with pravastatin
      10 to 20 mg/d on serum adiponection concentrations in patients with documented
      CAD and total cholesterol (TC) levels> or =180 mg/dL. Patients from 13 medical
      centers in Japan were monitored at visits every 4 weeks for assessment of
      compliance and adverse effects. For the assessment of pravastatin's effects,
      patients were categorized according to baseline serum adiponectin concentrations:
      quartile 1 (Q1) = < 4.83 microg/mL; quartile 2 (Q2) = 4.83 to 7.20 microg/mL;
      (Q4) = > 10.38 microg/mL. The primary end point of the study was the percent
      change from baseline in adiponectin nectin concentrations at 6 months. Secondary
      end points were changes in lipids, high-sensitivity C-reactive protein (hsCRP),
      and glycosylated hemoglobin (HbA1c). RESULTS: One hundred thirty consecutive
      patients were enrolled; 11 were excluded and 4 discontinued due to adverse
      events. Thus, 115 patients were included in the study analyses (83 men, 32 women;
      mean age, 68 years). No patient had a cardiac event during the 6-month follow-up
      period. After 6 months of pravastatin treatment, 74 (64.3%) patients had
      increases in serum adiponectin concentrations. Median (interquartile range)
      adiponectin concentrations increased significantly from 7.2 (4.8-10.4) mug/mL at
      baseline to 7.8 (5.4-11.2) microg/mL after 6 months of pravastatin treatment
      (P<0.001); the mean percent increase from baseline was 16.3%. The percent
      increase from baseline in serum adiponection concentrations was significantly
      higher among patients in Q1 (39.3%) compared with those in Q3 (4.5%) and Q4
      (6.3%) (P<0.003 and P<0.005, respectively). The relative increase in adiponectin
      concentrations was significantly correlated with the relative increase in high
      density lipoprotein cholesterol (HDL-C) (f=0.47; P<0.001). After 6 months of
      pravastatin treatment, TC and low-density lipoprotein cholesterol levels had
      decreased, by 14.6% and 23.3%, respectively, and HDL-C levels had increased by
      14.0% (all, P<0.001). The change in triglycerides (-13.3%) was not statistically
      significant. Serum hsCRP levels were significantly decreased from baseline after
      6 months of pravastatin treatment (P<0.001). HbA1c did not change significantly.
      CONCLUSION: In this pilot study in Japanese patients with CAD and
      hypercholesterolemia, 6 months of treatment with pravastatin 10 to 20mg/d was
      associated with significant increases in serum adiponectin concentrations.

PMID- 16990080
TI  - Rofecoxib 50 mg and valdecoxib 20 or 40 mg in adults and adolescents with
      postoperative pain after third molar extraction: results of two randomized,
      double-blind, placebo-controlled, single-dose studies.
AB  - OBJECTIVE: These studies assessed the comparative efficacy of rofecoxib and
      valdecoxib in the treatment of acute postoperative dental pain. METHODS: Two
      randomized, double-blind, placebo-controlled, single-dose studies were conducted
      in patients undergoing extraction of > or =2 third molars, with > or =1
      mandibular impaction, who experienced moderate or severe pain after extraction.
      In study 1, patients were randomized in a 4:4:1 ratio to receive rofecoxib 50 mg,
      valdecoxib 20 mg, or placebo. In study 2, which was an exploratory study,
      patients were randomized in a 2:2:1 ratio to receive reofecoxib 50 mg, valdecoxib
      40 mg, or palcebo. The primary efficacy end point was total pain relief at 12
      hours (TOPAR12) for rofecoxib compared with valdecoxib 20 mg (study 1) or
      valdecoxib 40 mg (study 2). Tolerability was assessed based on clinical adverse
      experiences (AEs) and vital signs. These studies were performed before both
      agents were withdrawn from the market. RESULTS: In study 1, 200 patients were
      randomized to receive rofecoxib 50 mg, 201 to valdecoxib 20 mg, and 49 to
      placebo. In study 2, 51 patients were randomized to receive rofecoxib 50 mg, 50
      to valdecoxib 40 mg, and 24 to placebo. The majority of patients in both studies
      were female (approximately 54%) and white ( approximately 66%), with a mean age
      of approximately 22 years and a mean weight of approximately 75 kg. Most
      (approximately 58%) patients reported experiencing moderate postoperative pain.
      In study 1, mean TOPAR12 scores were 30.7 for rofecoxib 50 mg, 28.9 for
      valdecoxib 20 mg, and 5.5 for placebo; in study 2, TOPAR12 scores were 27.0 for
      rofecoxib 50 mg, 28.6 for valdecoxib 40 mg, and 6.9 for placebo. In both studies,
      the active treatments were comparable in terms of the primary end point and were
      statistically superior to placebo (P<0.001). In study 1, rofecoxib was associated
      with a longer median time to use of rescue medication compared with valdecoxib 20
      mg (>24 hours vs 23 hours 58 minutes; P=0.010) and a significantly smaller
      proportion of patients using rescue medication over 24 hours (35.0% vs 50.2%;
      P<0.001). In study 2, there were no significant differences in the median time to
      use of rescue medication or the proportion of patients using rescue medication
      between active treatments. There were no significant differences in total pain
      relief at 4 or 8 hours, patients' global assessment, onset of analgesia, or AEs
      between active treatments in either study. The incidence of clinical AEs in study
      1 was similar for rofecoxib 50 mg, valdecoxib 20 mg, and placebo (39.5%, 36.8%,
      and 49.0%, respectively). In study 2, AEs occurred significantly less frequently
      with rofecoxib 50 mg compared with placebo (35.3% vs 70.8%, respectively;
      P<0.01); there was no significant difference between the rate of AEs with
      valdecoxib 40 mg (50.0%) and placebo. CONCLUSIONS: Rofecoxib 50 mg had comparable
      analgesic efficacy to valdecoxib 20 and 40 mg in these patients with pain after
      dental surgery. All active treatments were well tolerated.

PMID- 16990081
TI  - Influence of culture site-specific MIC distributions on the pharmacokinetic and
      pharmacodynamic properties of piperacillin/tazobactam and piperacillin: a data
      analysis.
AB  - BACKGROUND: Investigators who perform pharmacokinetic/pharmacodynamic (PK-PD)
      modeling with Monte Carlo simulation have historically not stratified
      microbiological data by culture site. This lack of stratification might be
      problematic if susceptibility patterns differ among sites and might lead to
      differences in PK-PD. OBJECTIVE: This study compared the PK-PD of 2 antimicrobial
      regimens against 5 gram-negative bacterial species form 3 culture sites. METHODS:
      This data analysis was performed at the Department of Pharmacology, The
      University of Texas Health Science Center, San Antonio, Texas. Blood, pulmonary
      (ie, bronchial, endotracheal, lung, respiratory, sputum, and tracheal
      secretions), and wound distributions of MICs were extracted from the 2002
      Intensive Care Unit Surveillance System database. Bacteria included Acinetobacter
      baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and
      Pseudomonas aeruginosa. The PK properties of piperacillin/tazobactam (3.375 g
      every 4 hours) and piperacillin (3 g every 4 hours) were obtained from studies in
      healthy volunteers. Monte Carlo simulation was used in 10,000 patients for each
      antimicrobial-bacteria-culture site combination. The cumulative fraction of
      response (CFR) for a free percentage time above the MIC of > or =50% was
      determined for each combination, and a clinically significant difference was
      defined a priori as > or =10%. RESULTS: Data from 2408 pulmonary, 490 blood, and
      242 wound isolates were included. For piperacillin/tazobactam, the CFR varied
      <10% by culture site in all 5 bacterial species. Site-specific differences were
      noted in MIC50 for piperacillin versus E cloacae and E coli and MIC90 for
      piperacillin/tazobactam versus K pneumoniae and P aeruginosa. Likewise, for
      piperacillin, the CFR was similar among the 3 culture sites for P aeruginosa.
      However, the CFR for piperacillin varied by > or =10% for A baumannii (blood >
      wound), E cloacae (pulmonary > blood), E coli (pulmonary and blood > wound), and
      K pneumoniae (wound > blood). CONCLUSIONS: The PK-PD models based on PK
      properties found in healthy humans and site-specific MIC distributions in this
      study suggest that for piperacillin, culture-site differences subsequently
      resulted in CFR differences that exceeded a predetermined level of clinical
      significance. Furthermore, these data suggest that traditional reporting
      strategies for microbiological data (ie, MIC50 and MIC90) might fail to
      adequately characterize the MIC population.

PMID- 16990082
TI  - The $64,000 question--what is a quality-adjusted life-year worth?

PMID- 16990083
TI  - Patient characteristics and patterns of drug use for sleep complaints in the
      United States: analysis of National Ambulatory Medical Survey data, 1997-2002.
AB  - OBJECTIVE: The aims of this work were to characterize ambulatory patients in the
      United States presenting with primary or secondary insomnia complaints and
      resultant diagnoses, and to describe the characteristics of patients treated with
      medications commonly used for sleep complaints. METHODS: Data from the National
      Ambulatory Medical Care Survey for the years 1997 through 2002 were analyzed.
      Data were stratified by patient characteristics, physician specialty, resulting
      diagnosis, and medications prescribed or provided. The unit of analysis was the
      individual patient visit; statistical comparisons were made using the chi(2) test
      for categorical variables and the Rao-Scott design-adjusted chi(2) test for
      comparisons of patient age groups. P<0.05 was the criterion for statistical
      significance. Cells containing < 30 observations were not included in the
      statistical analysis. RESULTS: The data included 147,945 patient visit records;
      rates of physician response to the survey ranged from 62.9% in 1999 to 70.4% in
      2002. Based on this sample, it was projected that 30 million office visits
      involved insomnia complaints over the 6-year period from 1997 to 2002 throughout
      the United States. With a total of 4.9 billion physician visits projected for
      that time period, 0.6% of visits were insomnia related. Women were 1.5 times more
      likely to have insomnia-related visits (P<0.001). Overall, the greatest
      proportion of insomnia patients of both sexes was between the ages of 18 and 64
      years (P<0.001). Sleep difficulties were most frequently attributed to organic
      disorders, depression and/or anxiety, and primary insomnia (55.8%, 27.3%, and
      9.8%, respectively; P<0.001). The most frequently prescribed or recommended
      medications were zaleplon/zolpidem and trazodone (28.5% and 32.0%, respectively;
      P<0.001). Zaleplon and zolpidem were most frequently used for patients with
      organic diagnoses and those aged < or =65 years (33.2% and 29.8%; P<0.001).
      CONCLUSIONS: Demographics of patients with insomnia and their diagnoses from 1999
      to 2002 remained stable, but the use of medications changed predictably as newer
      agents became available.

PMID- 16990084
TI  - Effectiveness and cost-effectiveness of facilitated percutaneous coronary
      intervention compared with primary percutaneous coronary intervention in patients
      with ST-segment elevation myocardial infarction transferred from community
      hospitals.
AB  - BACKGROUND: Primary percutaneous coronary intervention ([PCI], percutaneous
      transluminal coronary angioplasty+stenting) for ST-segment elevation myocardial
      infarction (STEMI) is regarded as superior to fibrinolysis even if it means that
      patients need to be transferred from one center to another to undergo the
      procedure. However, this inevitable delay between symptom onset and PCI, caused
      by the time required to travel, might increase the occurrence of cardiac events.
      A hybrid method called facilitated PCI uses fibrinolysis and/or glycoprotein (GP)
      IIb/IIIa inhibitors before transfer to a tertiary medical center where urgent PCI
      might be performed. This approach, however, has not been systematically
      evaluated. OBJECTIVE: The purpose of this study was to compare the effectiveness
      (combined end point of in-hospital mortality, reinfarction, stroke, or emergency
      revascularization) and cost-effectiveness of utilizing a bolus thrombolytic agent
      with GP IIb/IIIa inhibitor followed by transfer to a tertiary institution for
      facilitated PCI or standard of care transfer without primary PCI drugs among
      patients presenting to a community hospital with STEMI. METHODS: This was a
      prospective, single-center, cohort study comprising data from STEMI patients
      transferred from community hospitals to Hartford Hospital, Hartford, Connecticut,
      from the years 2000 to 2003. At the time of analysis, patients receiving primary
      PCI were matched (1:1) with those receiving facilitated PCI, utilizing propensity
      scores to assure similar demographics. The combined incidence of major adverse
      cardiac end points (MACE) and total hospital costs was compared between groups.
      Non-parametric bootstrapping was conducted to calculate CIs for the incremental
      cost-effectiveness ratio and generate a quadrant analysis. RESULTS: Based on 254
      propensity score-matched patients (127 facilitated PCI and 127 primary PCI), in
      hospital MACE and total hospital costs were reduced by 61.3% and US 4563 dollars
      (2005), respectively, in patients receiving facilitated compared with primary PCI
      (P=0.021 and P=NS, respectively). Patients receiving facilitated PCI were more
      likely to have target lesion Thrombolysis in Myocardial Infarction (TIMI) III
      (normal) blood flow on cardiac catheterization than those receiving primary PCI
      (49.6% vs 30.7%; P=0.002). However, the rate of TIMI bleeding was similar in both
      groups (21.3% in the facilitated PCI group vs 18.9% in the primary PCI group).
      Nonsignificant reductions were observed in both intensive care unit (ICU) and
      total length of stay (LOS) (0.8 day and 1.0 day, respectively) compared with the
      primary PCI group. Bootstrap analysis revealed that of 25,000 samplings,
      facilitated PCI would likely be both more effective and less costly 94.6% of the
      time. CONCLUSIONS: The use of facilitated PCI in STEMI patients who initially
      presented to community hospitals and were transferred for PCI appeared to
      significantly reduce the incidence of MACE, and increase the likelihood of having
      baseline TIMI III blood flow at time of catheterization. Nonsignificant
      reductions were observed in total ICU and hospital LOS. However, there did not
      appear to be a significant effect on the incidence of bleeding in patients
      receiving facilitated PCI. Bootstrap analysis confirmed that facilitated PCI
      would be both a more effective and less costly strategy.

PMID- 16990085
TI  - Proposed dose equivalence for rapid switching between dopamine agonists in
      Parkinson's disease.

PMID- 16990087
TI  - The checklist--a tool for error management and performance improvement.
AB  - Levels of cognitive function are often compromised with increasing levels of
      stress and fatigue, as is often the norm in certain complex, high-intensity
      fields of work. Aviation, aeronautics, and product manufacturing have come to
      rely heavily on checklists to aid in reducing human error. The checklist is an
      important tool in error management across all these fields, contributing
      significantly to reductions in the risk of costly mistakes and improving overall
      outcomes. Such benefits also translate to improving the delivery of patient care.
      Despite demonstrated benefits of checklists in medicine and critical care, the
      integration of checklists into practice has not been as rapid and widespread as
      with other fields. This narrative is a guide to the evolution of medical and
      critical care checklists, and a discussion of the barriers and risks to the
      implementation of checklists.

PMID- 16990088
TI  - Interdisciplinary communication: an uncharted source of medical error?

PMID- 16990090
TI  - Distribution and determinants of critical illness among status Aboriginal
      Canadians. A population-based assessment.
AB  - PURPOSE: The aim of the study is to determine the incidence, demographic risk
      factors, and outcomes of critical illness among all adult status Aboriginal
      Canadians (SACs) admitted to intensive care units (ICUs). PATIENTS AND METHODS: A
      population-based cohort was conducted among adult residents of the Calgary Health
      Region admitted to ICUs between May 1999 and April 2002. Patients were classified
      as SAC based on an alternate premium arrangement field within their Alberta
      personal health number. RESULTS: The annual incidence of critical illness among
      SACs of 620.6 per 100,000 was significantly higher than the non-SAC population of
      302.6 per 100,000 (RR, 2.1; 95% CI, 1.78-2.35); this was due to a 3-fold higher
      admission rate to the multisystem ICUs among SAC (579.6 per 100,000/y) as
      compared with non-SAC patients (210.7 per 100,000/y; RR, 2.75; 95% confidence
      interval [CI], 2.37-3.17). The highest risk for ICU admission among SAC patients
      was observed in those aged 20 to 49 years, and the incidence was higher in males
      than females (772.3 vs 479.8 per 100,000/y; RR, 1.6; 95% CI, 1.21-2.14). Although
      the in-hospital case-fatality rate was only slightly higher among SAC (18%,
      38/212) as compared with non-SAC patients (922/7,159; 13%; RR, 1.39; 95% CI, 1.04
      1.87), the annual mortality rate was much higher (146.4 per 100,000 for SAC vs
      60.9 per 100,000 for non-SAC; RR, 2.40; 95% CI, 1.78-3.19). CONCLUSION: This
      study demonstrates that SACs have an increased burden of critical illness as
      compared with the general non-SAC population and supports further research aimed
      at exploring means to reduce its adverse impact in this population.

PMID- 16990091
TI  - Narratives of critical care: the missing link.

PMID- 16990092
TI  - Liver failure, life support, family support, and palliation: an inside story.
AB  - My sister was admitted to the intensive-care-unit (ICU) five months before she
      died. At the time of admission her life-support wishes were not discussed with
      her. During her time in the ICU, we, the family, were given hope that she may
      survive. As with most families, we wanted my sister to live. During her
      progression from ICU to step-down unit to ward unit, the plan of care was not
      discussed, and goals were not set. Many medical teams were involved in my
      sister's care, and many looked at individual body parts instead of the whole
      person. I am a Registered Nurse at the same hospital where my sister was being
      cared for. Through many family meetings I was regarded as a medical professional,
      not as a sister. Knowing the medical system yet going through this as a family
      member has given me the opportunity to gain insight into what should have
      happened. If code status had been discussed we would have known my sisters
      wishes. If relevant literature pertaining to her disease and her slim chance of
      recovery had been brought to our attention, my sister could have died at home as
      she wished, and perhaps could have lived her final days in comfort.

PMID- 16990093
TI  - Early markers of acute respiratory distress syndrome development in severe trauma
      patients.
AB  - PURPOSE: The aim of the study was to identify early risk factors for development
      of acute respiratory distress syndrome (ARDS) in severe trauma patients.
      MATERIALS AND METHODS: This was a prospective observational study of 693 severe
      trauma patients (Injury Severity Score >or=16 and/or Revised Trauma Score <or=11)
      in 17 hospitals in a Spanish region of 8 million inhabitants from July 2002 to
      December 2002. RESULTS: Acute respiratory distress syndrome developed in 6.9% of
      patients who were more severely ill with higher APACHE II (P < .001) and Injury
      Severity Score (P = .002) scores vs patients not developing ARDS. Acute
      respiratory distress syndrome development was associated (P < .001) with
      fractures of femur (International Classification of Diseases, Ninth Revision [ICD
      9] codes 820, 821), tibia (ICD-9 code 823), humerus, and pelvis, with a number
      (>or=2) of long bone fractures, and with chest injuries (rib/sternal fracture
      [ICD-9 code 807] and hemo/pneumothorax [ICD-9 code 860/861]). Patients with ARDS
      required more colloids (P = .005) and red blood cell units (P = .02) than
      patients without ARDS during the first 24 hours. Multivariate analysis showed
      that ARDS was related to chest trauma diagnosis (ICD-9 code 807) (odds ratio
      [OR], 3.85), femoral fracture (OR, 3.16), APACHE II score (OR, 1.05), and blood
      transfusion during resuscitation (OR, 1.32). CONCLUSIONS: Risk of ARDS
      development is related to the first 24-hour admission variables, including severe
      physiologic derangements and specific ICD-9-classified injuries. Blood
      transfusion may play an independent role.

PMID- 16990094
TI  - C-reactive protein concentration as a predictor of intensive care unit
      readmission: a nested case-control study.
AB  - PURPOSE: The purpose of this study is to assess the ability of potential clinical
      predictors and inflammatory markers to predict intensive care unit (ICU)
      readmission during the same hospitalization. MATERIALS AND METHODS: A nested case
      control study utilized prospectively collected de-identified data of a 22-bed
      multidisciplinary ICU in a university hospital. RESULTS: There were 1,405
      consecutive ICU admissions in 2004, and of these, 18 were regarded as ICU
      readmissions (1.3%). The destination and timing of ICU discharge, the Sequential
      Organ Failure Assessment scores, white cell counts, and fibrinogen concentrations
      at discharge were not associated with ICU readmission. C-reactive protein (CRP)
      concentration within 24 hours before ICU discharge was associated with ICU
      readmission (mean CRP concentrations of cases vs controls, 177.8 vs 56.5 mg/L,
      respectively; P < .0001). The results remained unchanged after adjustment with
      the propensity scores. The area under the receiver operating characteristic curve
      for the CRP concentrations to predict ICU readmission was 0.884 (95% confidence
      interval, 0.765-0.999; P < .0001). Patients readmitted to the ICU had a higher
      predicted mortality in their second ICU admission (34.9% vs 26.1%; P < .01) and a
      longer total hospital stay (33.3 vs 20.3 days; P < .003) than patients without
      ICU readmission. CONCLUSIONS: A high CRP concentration within 24 hours before ICU
      discharge is associated with a higher risk of readmission to the ICU.

PMID- 16990095
TI  - C-reactive protein to predict intensive care unit readmission?

PMID- 16990096
TI  - Electromagnetic interference in critical care.
AB  - Mobile communication and wireless data transmission are playing an increasing
      role in health care. Reports describing medical device malfunction related to
      cellular phones have raised awareness about the problem of electromagnetic
      interference. Although initial institutional responses were to ban cellular
      devices in hospitals, these restrictions are relaxing as the knowledge base in
      this area expands. Medical device malfunction is extremely rare if the distance
      from the transmitting device is greater than 1 m. This article reviews the
      current understanding of electromagnetic interference as it applies to the
      technology-rich critical care environment.

PMID- 16990097
TI  - The Pediatric Early Warning System score: a severity of illness score to predict
      urgent medical need in hospitalized children.
AB  - PURPOSE: We developed and performed the initial retrospective validation of a
      pediatric severity of illness score. The score is to preemptively identify
      hospitalized children who are likely to require resuscitation to treat
      cardiopulmonary arrest. MATERIALS AND METHODS: The Pediatric Early Warning System
      (PEWS) score was developed using expert opinion. The score generated contained 20
      items, 16 of which were able to be retrospectively abstracted. Validation used a
      case-control study design in a Canadian university-affiliated pediatric hospital.
      Eligible patients were younger than 18 years, were admitted to a hospital ward,
      and had no level-of-care restrictions. Case patients had a code blue called to
      obtain immediate assistance for treatment of impending or actual cardiopulmonary
      arrest. Control patients had no code blue event and were not urgently admitted to
      the intensive care unit within 48 hours of study. A total of 128 controls and 87
      cases were compared. RESULTS: The PEWS score area under the receiver operating
      characteristic curve was 0.90. The sensitivity was 78% and the specificity was
      95% at a score of 5. CONCLUSIONS: Application of the score may have identified
      more than 3 quarters of code blue calls in our hospital with at least an hour's
      warning. After further refinement and validation, the PEWS score has great
      potential to increase the efficiency of care delivery and to improve the outcomes
      of care provided to hospitalized children.

PMID- 16990098
TI  - The PEWS score: potential calling criteria for critical care response teams in
      children's hospitals.

PMID- 16990099
TI  - Heart rate variability monitoring in the detection of central nervous system
      complications in children with enterovirus infection.
AB  - PURPOSE: Previous studies suggest the possibility of autonomic dysfunction in
      patients with complicated hand, foot, and mouth disease (HFMD) and herpangina.
      Heart rate variability (HRV), an index for autonomic nervous system, may be
      useful to detect disease progression. MATERIALS AND METHODS: From 2001 to 2002,
      66 patients (1-9 years old) were enrolled prospectively in either a control (20
      patients) or disease (46 patients with HFMD or herpangina) group. The disease
      group was subdivided into stage I (fever only), stage II (with complications of
      encephalomyelitis), and stage III (with complications of encephalomyelitis as
      well as tachycardia, hyperglycemia, tachypnea, and hypertension or hypotension)
      groups. Data from electrocardiograms were transformed for HRV. RESULTS: The HRV
      parameters generally decreased and the low frequency (LF)/high frequency ratio
      (HF) increased in the disease groups. Patients in disease group stage II had
      significantly lower parameters of HRV (triangular index, total power, LF power,
      and HF power) and higher LF/HF ratio than those in disease group stage I. With
      this trend, patients with stage III disease had extremely low HRV parameters. The
      inferred criteria of HRV (standard deviation of normal-to-normal interval <17
      milliseconds and HF power <24 milliseconds(2)) to define stage III patients
      (sensitivity, 100%; specificity, 71.4%) were also useful to predict disease
      progression. CONCLUSIONS: The HRV markedly decreased, most likely because of
      autonomic dysfunction, in patients with HFMD and herpangina when complicated with
      central nervous system involvement and cardiopulmonary failure and may be useful
      parameters to monitor disease progression.

PMID- 16990100
TI  - Heart rate variability and infection: diagnosis, prognosis, and prediction.

PMID- 16990102
TI  - Re: Regional citrate anticoagulation does not prolong filter survival during
      CVVH.

PMID- 16990104
TI  - The pathophysiology of the hairy cell.
AB  - HCs are clonal late B cells that are related to memory cells and display specific
      features of activation. Many of the distinctive features of HCs (eg, morphology,
      TRAP) are related to this specific activation. Many of the distinctive histologic
      features of HCL can be related to constitutive production of cytokines (eg, FGF,
      fibrosis) and to the expression/activation of adhesion receptors (eg,
      alpha(4)beta(1), alpha(5)beta(1) and alpha(v)beta(3) integrins, CD44v3). HCs
      usually have mutated IGVH genes and have no consistent or specific chromosome
      abnormalities (5q additions and 7q deletions in a minority). The signals that are
      responsible for several of the phenotypic features of HCs have been identified,
      but the nature of the underlying oncogenic events remains unknown.

PMID- 16990105
TI  - Hairy cell leukemia: diagnostic pathology.
AB  - The pathology of HCL has been reviewed with a focus on the diagnostic
      hematopathology of this rare, but fascinating, disease. The discrimination of HCL
      from other B-cell lymphoproliferations, particularly HCL-V and SMZL, has been
      emphasized. The unique responsiveness of HCL to 2-CdA and other chemotherapeutic
      agents makes this distinction critical. Fortunately, HCL has consistent
      cytologic, histologic, cytochemical, and immunologic features that make
      classification reliable and reproducible. Less straightforward is the
      differential diagnosis of SMZL and HCL-V, problematic because of the rarity of
      both disorders, lack of discriminating evidence-based criteria, and perhaps a
      biologic kinship between these two disorders that share many clinical and
      pathologic features. Fortunately, this is not a clinically critical distinction.

PMID- 16990106
TI  - Immunophenotyping and differential diagnosis of hairy cell leukemia.
AB  - HCL and HCL-variant cells have a distinct immunophenotype that seems to
      correspond to that of a mature activated memory B cell. Although the two diseases
      have similarities in histology and membrane marker expression, such as the
      selected Ig heavy-chain expression and the reactivity with certain B-cell
      activation markers (eg, CD103), there are differences in their clinical course,
      morphology, and immunophenotype. Immunophenotyping is an essential tool for the
      diagnosis of these two disorders, for monitoring and assessing response to
      therapy, and for distinguishing them from other B-cell malignancies.

PMID- 16990107
TI  - Clinical presentations and complications of hairy cell leukemia.
AB  - HCL typically presents in middle-aged men, and is characterized by splenomegaly
      and cytopenias. Hepatomegaly may be present, but it usually is not a salient
      feature. Peripheral adenopathy is uncommon. Other organ manifestations occur, but
      are unusual. patients are now presenting with a less tumor burden, as a result of
      earlier diagnosis. Leukocytosis/lymphocytosis should suggest HCl variant.
      Infectious complications, which were common in the past and the major cause of
      death, have become rare in the era of purine analog therapy. Whether there is a
      true increased risk for second malignancies remains controversial.

PMID- 16990108
TI  - Splenectomy, interferon, and treatments of historical interest in hairy cell
      leukemia.
AB  - The evolution and "lessons learned" for therapeutic options and approaches in
      HCL, which subsequently evolved into the adenosine deaminase inhibitors as the
      treatment of choice, has been intriguing. The contributions to patient care and
      individual patient lives have been remarkable. Observation, splenectomy, and
      recombinant interferon are potential therapeutic are alternatives in select
      patients as initial therapy, and as therapeutic alternatives in the 10% of
      patients who have progressive disease after the purine nucleoside analogs.

PMID- 16990109
TI  - Purine analogues: rationale for development, mechanisms of action, and
      pharmacokinetics in hairy cell leukemia.
AB  - Cladribine is effective therapy for HCL, and there are several ways to achieve
      the adequate concentrations of the active metabolites in relevant cells, without
      the need for long-term continuous infusions. This simplifies therapy, although
      careful control of patients is required during and after treatment in most
      instances because of the significant activity of the drug on leukemia cells of
      various types and also on lymphoid cells and normal stem cells.

PMID- 16990110
TI  - Pentostatin: impact on outcome in hairy cell leukemia.
AB  - Major advances in the management of patients who have hairy cell leukemia have
      been made following the use of purine nucleoside analogs. Pentostatin and
      cladribine are equally effective, and have impressive long-term effectiveness.
      Although the degree of myelosuppression may be less with the use of pentostatin,
      this may reflect differences in the schedule and dose of drug administration
      between these agents. The gradual, but relentless, improvement in the peripheral
      blood counts enables out-patient management with pentostatin in most patients.
      Cladribine affords the convenience of a single course of administration. A direct
      comparative study with these two agents is unlikely to yield the optimal
      management of patients who have minimal residual disease following the
      administration of either agent is warranted in the context of a clinical trial.
      Patients do relapse, and the overall survival curves have not reached a plateau,
      which indicates that cure has not been secured. The satisfaction of having
      improved the outcome for patients who have this previously untreatable leukemia
      should not give way to complacency for further improvement in the management of
      this disease. Future studies should be directed to optimizing the therapy for
      minimal residual disease as well as clearer definition of supportive care.

PMID- 16990111
TI  - Cladribine in hairy cell leukemia.
AB  - Cladribine results in prolonged complete remissions in most patients wo have HCL.
      Several studies have indicated that patients who are in complete remission have
      survivals that are comparable to those of normal age-matched controls. HCL
      related mortality is distinctly uncommon. Nevertheless, it is unlikely that
      cladribine treatment of HCL is curative because MRD is common in the bone marrows
      of complete responders. Response criteria for HCL include clinical, hematologic,
      and morphologic criteria, but do not include flow cytometry, immunohistochemical
      analysis, or molecular studies. More sensitive techniques have been used by
      Filleul and colleagues to detect MRD. The used clonoegenic probes from the
      hypervariable regions of the immunoglobulin heavy-chain gene and performed
      polymerase chain reactions (PCRs) on bone marrow biopsy specimens, All seven
      patients who were in morphologic complete remission after a single cladribine
      infusion were PCR positive. These data indicate that cladribine induces
      protracted remissions but is not necessarily curative. MRD can be detected in
      most patients when sensitive techniques are used. Persistence of
      immunohistochemical MRD may predict detected MRD remains to be studied in a large
      number of patients. Investigators from the University of Pisa in Italy have used
      a combination of cladribine and rituximab to eradicate MRD in patients who have
      HCL. Ten patients received treatment with a standard infusion of cladribine. Two
      patients achieved a complete remission, 6 patients achieved a partial remission,
      and 2 patients failed to respond. All were PCR positive for the immunoglobulin
      heavy-chain (IgH) gene product at the completion of cladribine treatment. All 10
      patients had achieved a complete hematologic response 2 months after the
      completion of ritximab therapy. The curative nature of this treatment will
      require long-term follow-up. Cladribine represents a major therapeutic advance in
      the treatment of HCL. The prognosis of patients who have HCL has improved greatly
      with cladribine therapy. Future strategies should address combination therapy
      with purine analogs and monclonal antibodies. These strategies should address
      eradication of MRD in an attempt to develop a potentially curative combination
      treatment program.

PMID- 16990112
TI  - Monoclonal antibody therapy for hairy cell leukemia.
AB  - The use of MoAb therapy for the treatment of HCL offers great promise and
      potential for improving progression-free survival. Rituximab has activity in the
      setting of previously treated HCL and the ability to eradicate MRD after 2-CdA
      given as frontline therapy. Alemtuzumab, epratuzumab, Hu-Max-CD20, and other
      candidate MoAb's should be studied in HCL. Appropriate pharmacologic
      investigation, use of antigen modulation, and assessments of soluble antigen
      levels should be considered with future clinical trial s of MoAb's in HCL to
      optimize therapeutic strategies.

PMID- 16990114
TI  - Hairy cell leukemia: towards a curative strategy.
AB  - Although not all patients who have HCL require therapy at diagnosis, most
      eventually need treatment. Historically, splenectomy and interferon-alpha
      resulted in hematologic responses; however, responses tend to be short. The
      introduction of purine analogs dramatically changed the prognosis for most
      patients who hae HCL. It is now considered standard of care to use a purine
      analog, such as 2-CdA or 2'-DCF, as first-line therapy. This approach results in
      a high CR rate and prolong DFS. Although both agents yield the same rates of CR
      and survival, 2-CdA seems easier to administer and my be associated with less
      toxicity. Despite the excellent results with purine analogs, most patients have
      MRD detected by sensitive techniques; 30% to 40% of patients eventually relapse
      and most require further therapy. A repeat course of 2-CdA (or 2'-DCF) will
      result in CR in approximately 70% of patients. For patients who have relapsed or
      refractory disease, monoclonal antibody-based therapies are emerging options.
      Rituximab and BL22 are highly active in this setting. Until BL22 becomes widely
      available, rituximab is a reasonable choice for salvage therapy; however, the
      dosing schedule needs to be denied further. The roles of rituximab and BL22 as
      initial therapy for patients who have previously untreated HCL have not been
      investigated. Fig. 1 is a suggested algorithm for the treatment of HCL. With the
      introduction of effective new agents, further studies will determine whether the
      now achievable prolonged survival will translate into cure.

PMID- 16990113
TI  - Immunotoxins in the treatment of refractory hairy cell leukemia.
AB  - An increasing number of patients who have hairy cell leukemia (HCL) have
      persistent disease that requires treatment, despite purine analogs, splenectomy,
      interferon, and rituximab. Many of these patients have been treated successfully
      with immunotoxins. An immunotoxin contains a protein toxin connected to a cell
      binding ligand, such as an antibody. An immunotoxin recognizes the target cell,
      internalizes, and the toxin translocates to the cytosol where it inhibits protein
      synthesis enzymatically. Immunotoxins that show activity in HCL contain truncated
      Psedomonas exotoxin fused to the Fv fragments of anti-CD25 or anti-CD22
      monoclonal antibodies. Both agents, termed LMB-2 and BL22, respectively, have
      been tested in patients who have HCL after failure of purine analogs and other
      therapies; major responses have been achieved in most patients.

PMID- 16990115
TI  - Nursing within a global context.

PMID- 16990117
TI  - Interdisciplinary research: the role of nursing education.

PMID- 16990118
TI  - A community partnership model for developing a Center for Cancer Nursing
      Education and Research.
AB  - This article describes a partnership model used to establish the Center for
      Cancer Nursing Education and Research at the University of Louisville (U of L)
      School of Nursing. The model was used to bring together area nursing education
      programs, institutions providing cancer nursing care, and related community
      groups. The need for the project was directly related to the high cancer
      morbidity and mortality in the community. The U of L's strategic agenda and
      strong commitment to cancer prevention and care provided a growth opportunity for
      the recognition of nurses' role in cancer care. Nurses are positioned to
      influence cancer care across the continuum from prevention to end of life, and
      building the capacity for cancer nursing is essential to building a system of
      cancer care. This article describes an innovative partnership model used to
      stimulate a community-wide focus on cancer nursing. The organizational structure,
      development of partner relationships, description of project activities, and
      outcomes are presented along with a discussion of the said model's benefits and
      potential for replication.

PMID- 16990119
TI  - Improving perceptions of patient care--a nursing education and nursing practice
      initiative.
AB  - In January 2005, the University of Texas Medical Branch (UTMB) School of Nursing
      and the UTMB Hospitals and Clinics launched the first phase of a project to
      improve perceptions of patient care on the part of nursing faculty and nursing
      clinicians. A finding on the UTMB annual employee satisfaction survey that
      nursing faculty and clinicians tended to rate quality of UTMB patient care lower
      than other UTMB employees provided the impetus for the initiative. When UTMB
      colleagues noticed the findings, various entities including human resources and
      the Faculty Senate called for explanations from the dean of the School of
      Nursing, the chief nursing officer, and the CEO for the hospitals and clinics. In
      the process of attempting to give reasons for the findings, each of us determined
      we would take definitive action to address the situation. This article describes
      our accomplishments for Phase 1 of the initiative. Beginning with a vision for a
      productive professional community characterized by a pedagogical partnership
      between nursing education and practice, we share the processes we followed to (1)
      achieve mutual understanding among task force members, (2) obtain input on
      perceptions from nursing colleagues, (3) identify the clinical and nursing
      education aspects of the perceptions, (4) reach consensus on target perceptions
      for Phase 2 of the project, and (5) outline the next steps for the project.

PMID- 16990120
TI  - Training efforts to reduce reports of workplace violence in a community health
      care facility.
AB  - The objective of this study was to measure reports of workplace violence (WPV)
      after an online training program on WPV for health care workers. Recognition of
      the prevalence of WPV (physical, emotional-verbal, and sexual) suggests a great
      need for employers to provide training to all health care workers as a first-line
      effort to reduce or prevent WPV. A 3-hour online training program for WPV was
      offered to 43 workers attending an informational session. Volunteers included 22
      participants designated for training and 21 volunteers designated to serve as
      control subjects. Pretraining WPV work area assessments were completed by all
      participants and compared between training participants and control subjects. At
      6 months, comparisons were made between 3 groups: Group A, those who completed
      the training; Group B, control subjects; and Group C, those who did not complete
      the training within the designated period. Group C was defined as a separate
      group because some participants within this group were workers from the same work
      areas as were Group A participants. Comparisons of preassessments and
      postassessments of WPV for Group A and assessments of WPV across the three groups
      were made. Participants reported 200 WPV events over a 6-month period before
      training. Pretraining reports of WPV were statistically different between
      training participants and control subjects for total and emotional-verbal WPV
      events. At 6 months after the training, a reduction in sample size and reports of
      all types of WPV was noted across the three groups (i.e., those who completed the
      training, those who did not complete it, and control subjects). Owing to the
      small number of reported physical and sexual WPV events, only total and emotional
      verbal WPV events were examined. No difference was noted between the three groups
      for total events; however, emotional-verbal abuse was statistically significant
      between the groups. In addition, a statistically significant difference was noted
      among participants before and after the completion of the online training.
      Despite the reported prevalence of WPV, a significant number of health care
      workers did not make training a priority. Participants who were designated for
      training and who subsequently completed it reported the most number of events
      before and after training. Proportionately per number of participants after
      training, fewer total WPV events were reported; however, because of the attrition
      rate and group sample size, significance was not reached. Reports of emotional
      verbal abuse remained high after training, which could suggest a heightened
      awareness of this type of WPV with a personal redefinition of WPV or a heightened
      staff and administration sensitivity to reporting. Although differences existed
      among training participants and control subjects before training, significance
      could not be achieved among the three groups owing to validity threats, including
      subject mortality, diffusion between groups, selection bias, and small sample
      size. However, the finding that training can make a difference is important and
      encourages replication of this study with a larger sample size and a larger
      setting. Finding high rates of emotional-verbal abuse across work areas and
      support for training benefits enhance the need for training programs with an
      increased focus on emotional-verbal WPV.

PMID- 16990121
TI  - Outcomes of scholarly inquiry: an analysis of Master's of Nursing students'
      projects/theses.
AB  - This study examined the first scholarly projects/theses of 112 graduates of a
      newly formed Master of Nursing (MN) program. The purpose of the analysis was to
      determine whether MN graduates' scholarly projects/theses addressed the American
      Association Colleges of Nursing's (1996) Essentials of Master's Education for
      Advanced Practice Nursing, met program outcomes, and adhered to campus and
      program values. Other specific questions were formulated to ascertain the method
      of inquiry most used, the population group most examined, and the outcomes of the
      inquiry. The sample of 106 scholarly projects and six theses were categorized
      according to method of inquiry, population group, population type, and scholarly
      outcomes and then entered into a database software program. The findings showed
      the method of inquiry most used was literature review, followed by program
      critique, community assessment, and secondary analysis. The community was the
      most frequently examined population group, with patient, children, provider,
      minority, and elderly the most used population type. The most frequent scholarly
      outcomes were recommendations, study reports, educational materials, and program
      development. Findings supported the campus's and program's mission statement that
      values community partnership and diversity, improved health care outcomes, as
      well as an outcome objective of master's-level proficiencies in research
      competencies.

PMID- 16990122
TI  - A national needs assessment of nurses providing health care to adolescents.
AB  - Nurses, as the largest group of health providers in the United States, and by
      virtue of their scope of practice, are in an important position to promote the
      health of adolescents. A national survey of nurse members of the American Public
      Health Association, the National Association of Pediatric Nurse Associates and
      Practitioners, and the National Association of School Nurses was conducted in
      1997 (n = 520) and was compared with findings from a parallel survey conducted in
      1985 that assessed perceived competence in addressing common adolescent health
      issues, relevance of those issues to nurses' practice, and leadership skills.
      Findings provided a hopeful yet cautious picture of nurses' competencies. Strong
      increases in the proportion of nurses who felt equipped to address common health
      problems of youth suggest improved adolescent health education among nurses. Yet,
      at least 25% of nurses indicated a low level of knowledge in half of the
      adolescent health areas, and, like 1985's nurses, most nurses in 1997 did not
      feel competent to address the needs of gay, lesbian, and bisexual youth. Several
      priority areas in Healthy People 2010 were considered by 25% or more of the
      nurses to be irrelevant to their practice, including smoking cessation, suicide,
      violence, and pregnancy. The task remains to assure that all nurses who work with
      adolescents are equipped to respond to their diverse and unique health needs.

PMID- 16990123
TI  - Student nurses' attitudes and beliefs about breast-feeding.
AB  - This study explored the breast-feeding attitudes and beliefs of students newly
      enrolled in an urban university baccalaureate nursing program. A qualitative
      approach was used to conduct in-depth semistructured interviews with 12 students
      prior to their formal course work in maternal-child nursing. Four themes emerged
      from the data analysis: 1. Personal experiences are important in the development
      of breast-feeding attitudes and beliefs. 2. The students generally believed that
      breast-feeding offered benefits for babies and mothers, but the beliefs were
      stronger for those who grew up with breast-feeding as the norm. 3. All the
      students believed that there were barriers to breast-feeding in the United States
      that they identified as the societal view of the breast, dependence/independence
      conflicts, and concerns about intimacy. 4. The students identified an educational
      rather than promotional role for nurses in breast-feeding because of conflicts
      about personal choice. This study suggests that students need help identifying
      their attitudes and beliefs about breast-feeding and reflecting how their
      personal experiences influence breast-feeding promotion.

PMID- 16990124
TI  - Ensuring NCLEX-RN success for first-time test-takers.
AB  - A major indicator of baccalaureate nursing program effectiveness is the pass rate
      on the National Council Licensure Examinations, Registered Nurse (NCLEX-RN) among
      first-time candidates. This article highlights the scope, instructional methods,
      and outcomes of the remediation program at Georgetown University School of
      Nursing & Health Studies (GU-NHS). With implementation of the multifaceted
      program, the NCLEX-RN pass rate for first-time takers at GU-NHS has been
      consistently above the national mean among all first-time candidates. Although it
      is impossible to determine which strategy made the greatest contribution to the
      success of the program, the cumulative effect is impressive and indicates the
      students are prepared for the challenge of the examination and contemporary
      nursing practice.

PMID- 16990125
TI  - Lasker Laurels for telomerase.
AB  - This year the Lasker Foundation pays tribute to telomerase, a medically important
      enzyme required for chromosome stability and long-term cell proliferation.

PMID- 16990126
TI  - A quick release mechanism for abscisic acid.
AB  - The hormone abscisic acid regulates development and survival of plants in
      response to environmental stresses. now demonstrate that in response to stress,
      abscisic acid can be made available via polymerization of a beta-glucosidase
      enzyme. This enzyme is reported to hydrolyze glucose-conjugated abscisic acid,
      thus increasing active abscisic acid concentrations.

PMID- 16990127
TI  - The first high-resolution DNA "methylome".
AB  - Cytosine methylation plays a crucial role in the regulation of gene expression
      and the control of genome stability in higher eukaryotes. Despite its importance
      for normal development, the degree and genome-wide distribution of DNA
      methylation has remained largely unknown. In this issue of Cell, fill this gap by
      presenting a high-resolution map of DNA methylation in the genome of the
      flowering plant Arabidopsis.

PMID- 16990128
TI  - Caspase-1 builds a new barrier to infection.
AB  - Caspase-1 promotes both the maturation of proinflammatory cytokines and apoptosis
      in cells infected by certain pathogens. Work by now reveals a surprising new
      function for caspase-1: the stimulation of membrane biogenesis to repair damage
      caused by bacterial pore-forming toxins. Thus, caspase-1 may promote host cell
      survival as a means of resistance to pathogenic bacteria.

PMID- 16990129
TI  - A one-sided view of kinetochore attachment in meiosis.
AB  - Meiosis includes a reductional division in which homologous chromosomes, rather
      than sister chromatids, are segregated to opposite poles of the spindle. In this
      issue of Cell, report that casein kinase 1 contributes to this process by
      promoting the attachment of both kinetochores of a homolog to only one pole of
      the meiotic spindle in budding yeast.

PMID- 16990130
TI  - Brain evolution and uniqueness in the human genome.
AB  - Despite an ever-expanding database of sequenced mammalian genomes to be mined for
      clues, the emergence of the unique human brain remains an evolutionary enigma. In
      their new study, trawl the human genome and those of other mammals in search of
      short conserved DNA elements that show extremely rapid evolution only in humans.
      As they report in a recent issue of Nature, their scan yielded a gene for a novel
      noncoding RNA that adopts a human-specific structure and may regulate
      neurodevelopment.

PMID- 16990131
TI  - Making or breaking the heart: from lineage determination to morphogenesis.
AB  - The cues governing cardiac cell-fate decisions, cardiac differentiation, and
      three-dimensional morphogenesis are rapidly being elucidated. Several themes are
      emerging that are relevant for childhood and adult heart disease and the growing
      field of stem cell biology. This review will consider our current understanding
      of cardiac cell-fate determination and cardiogenesis--largely derived from
      developmental studies in model organisms and human genetic approaches--and
      examine future implications for diagnosis, prevention, and treatment of heart
      disease in the young and old.

PMID- 16990132
TI  - Monopolar attachment of sister kinetochores at meiosis I requires casein kinase
      1.
AB  - In meiosis, a single round of DNA replication is followed by two consecutive
      rounds of chromosome segregation, called meiosis I and II. Disjunction of
      maternal from paternal centromeres during meiosis I depends on the attachment of
      sister kinetochores to microtubules emanating from the same pole. In budding
      yeast, monopolar attachment requires recruitment to kinetochores of the monopolin
      complex. How monopolin promotes monopolar attachment was unclear, as its subunits
      are poorly conserved and lack similarities to proteins with known functions. We
      show here that the monopolin subunit Mam1 binds tightly to Hrr25, a highly
      conserved casein kinase 1 delta/epsilon (CK1delta/epsilon), and recruits it to
      meiosis I centromeres. Hrr25 kinase activity and Mam1 binding are both essential
      for monopolar attachment. Since CK1delta/epsilon activity is important for
      accurate chromosome segregation during meiosis I also in fission yeast,
      phosphorylation of kinetochore proteins by CK1delta/epsilon might be an
      evolutionary conserved process required for monopolar attachment.

PMID- 16990133
TI  - DEP-domain-mediated regulation of GPCR signaling responses.
AB  - G protein-coupled receptors (GPCRs) mediate cellular responses to a variety of
      stimuli, but how specific responses are regulated has been elusive, as the types
      of GPCRs vastly outnumber the classes of G protein heterotrimers available to
      initiate downstream signaling. In our analysis of signaling proteins containing
      DEP domains ( approximately 90 residue sequence motifs first recognized in fly
      Dishevelled, worm EGL-10, and mammalian Pleckstrin), we find that DEP domains are
      responsible for specific recognition of GPCRs. We examined the yeast regulator of
      G protein signaling (RGS) protein Sst2 and demonstrate that the DEP domains in
      Sst2 mediate binding to its cognate GPCR (Ste2). DEP-domain-mediated tethering
      promotes downregulation by placing the RGS protein in proximity to its substrate
      (receptor-activated Galpha subunit). Sst2 docks to the Ste2 cytosolic tail, but
      only its unphosphorylated state, allowing for release and recycling of this
      regulator upon receptor desensitization and internalization. DEP-domain-mediated
      targeting of effectors and regulators to specific GPCRs provides a means to
      dictate the nature, duration, and specificity of the response.

PMID- 16990134
TI  - Ligand-induced asymmetry in histidine sensor kinase complex regulates quorum
      sensing.
AB  - Bacteria sense their environment using receptors of the histidine sensor kinase
      family, but how kinase activity is regulated by ligand binding is not well
      understood. Autoinducer-2 (AI-2), a secreted signaling molecule originally
      identified in studies of the marine bacterium Vibrio harveyi, regulates quorum
      sensing responses and allows communication between different bacterial species.
      AI-2 signal transduction in V. harveyi requires the integral membrane receptor
      LuxPQ, comprised of periplasmic binding protein (LuxP) and histidine sensor
      kinase (LuxQ) subunits. Combined X-ray crystallographic and functional studies
      show that AI-2 binding causes a major conformational change within LuxP, which in
      turn stabilizes a quaternary arrangement in which two LuxPQ monomers are
      asymmetrically associated. We propose that formation of this asymmetric
      quaternary structure is responsible for repressing the kinase activity of both
      LuxQ subunits and triggering the transition of V. harveyi into quorum-sensing
      mode.

PMID- 16990135
TI  - Activation of glucosidase via stress-induced polymerization rapidly increases
      active pools of abscisic acid.
AB  - Abscisic acid (ABA) is a phytohormone critical for plant growth, development, and
      adaptation to various stress conditions. Plants have to adjust ABA levels
      constantly to respond to changing physiological and environmental conditions. To
      date, the mechanisms for fine-tuning ABA levels remain elusive. Here we report
      that AtBG1, a beta-glucosidase, hydrolyzes glucose-conjugated, biologically
      inactive ABA to produce active ABA. Loss of AtBG1 causes defective stomatal
      movement, early germination, abiotic stress-sensitive phenotypes, and lower ABA
      levels, whereas plants with ectopic AtBG1 accumulate higher ABA levels and
      display enhanced tolerance to abiotic stress. Dehydration rapidly induces
      polymerization of AtBG1, resulting in a 4-fold increase in enzymatic activity.
      Furthermore, diurnal increases in ABA levels are attributable to polymerization
      mediated AtBG1 activation. We propose that the activation of inactive ABA pools
      by polymerized AtBG1 is a mechanism by which plants rapidly adjust ABA levels and
      respond to changing environmental cues.

PMID- 16990136
TI  - The orphan nuclear receptor RORgammat directs the differentiation program of
      proinflammatory IL-17+ T helper cells.
AB  - IL-17-producing T lymphocytes have been recently shown to comprise a distinct
      lineage of proinflammatory T helper cells, termed Th17 cells, that are major
      contributors to autoimmune disease. We show here that the orphan nuclear receptor
      RORgammat is the key transcription factor that orchestrates the differentiation
      of this effector cell lineage. RORgammat induces transcription of the genes
      encoding IL-17 and the related cytokine IL-17F in naive CD4(+) T helper cells and
      is required for their expression in response to IL-6 and TGF-beta, the cytokines
      known to induce IL-17. Th17 cells are constitutively present throughout the
      intestinal lamina propria, express RORgammat, and are absent in mice deficient
      for RORgammat or IL-6. Mice with RORgammat-deficient T cells have attenuated
      autoimmune disease and lack tissue-infiltrating Th17 cells. Together, these
      studies suggest that RORgammat is a key regulator of immune homeostasis and
      highlight its potential as a therapeutic target in inflammatory diseases.

PMID- 16990137
TI  - Caspase-1 activation of lipid metabolic pathways in response to bacterial pore
      forming toxins promotes cell survival.
AB  - Many pathogenic organisms produce pore-forming toxins as virulence factors.
      Target cells however mount a response to such membrane damage. Here we show that
      toxin-induced membrane permeabilization leads to a decrease in cytoplasmic
      potassium, which promotes the formation of a multiprotein oligomeric innate
      immune complex, called the inflammasome, and the activation of caspase-1.
      Further, we find that when rendered proteolytic in this context caspase-1 induces
      the activation of the central regulators of membrane biogenesis, the Sterol
      Regulatory Element Binding Proteins (SREBPs), which in turn promote cell survival
      upon toxin challenge possibly by facilitating membrane repair. This study
      highlights that, in addition to its well-established role in triggering
      inflammation via the processing of the precursor forms of interleukins, caspase-1
      has a broader role, in particular linking the intracellular ion composition to
      lipid metabolic pathways, membrane biogenesis, and survival.

PMID- 16990138
TI  - The RCK domain of the KtrAB K+ transporter: multiple conformations of an
      octameric ring.
AB  - The KtrAB ion transporter is a complex of the KtrB membrane protein and KtrA, an
      RCK domain. RCK domains regulate eukaryotic and prokaryotic membrane proteins
      involved in K(+) transport. Conflicting functional models have proposed two
      different oligomeric arrangements for RCK domains, tetramer versus octamer. Our
      results for the KtrAB RCK domain clearly show an octamer in solution and in the
      crystal. We determined the structure of this protein in three different octameric
      ring conformations that resemble the RCK-domain octamer observed in the MthK
      potassium channel but show striking differences in size and symmetry. We present
      experimental evidence for the association between one RCK octameric ring and two
      KtrB membrane proteins. These results provide insights into the quaternary
      organization of the KtrAB transporter and its mechanism of activation and show
      that the RCK-domain octameric ring model is generally applicable to other ion
      transport systems.

PMID- 16990139
TI  - Crystal structures of a ligand-free MthK gating ring: insights into the ligand
      gating mechanism of K+ channels.
AB  - MthK is a prokaryotic Ca(2+)-gated K(+) channel that, like other ligand-gated
      channels, converts the chemical energy of ligand binding to the mechanical force
      of channel opening. The channel's eight ligand-binding domains, the RCK domains,
      form an octameric gating ring in which Ca(2+) binding induces conformational
      changes that open the channel. Here we present the crystal structures of the MthK
      gating ring in closed and partially open states at 2.8 A, both obtained from the
      same crystal grown in the absence of Ca(2+). Furthermore, our biochemical and
      electrophysiological analyses demonstrate that MthK is regulated by both Ca(2+)
      and pH. Ca(2+) regulates the channel by changing the equilibrium of the gating
      ring between closed and open states, while pH regulates channel gating by
      affecting gating-ring stability. Our findings, along with the previously
      determined open MthK structure, allow us to elucidate the ligand gating mechanism
      of RCK-regulated K(+) channels.

PMID- 16990140
TI  - A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis.
AB  - Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles
      that have been primed for release by SNARE-complex assembly. Besides
      synaptotagmin 1, fast Ca(2+)-triggered exocytosis requires complexins.
      Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is
      unclear how their functions are coupled. Here we propose that complexin binding
      activates SNARE complexes into a metastable state and that Ca(2+) binding to
      synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable
      SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin
      1 competes with complexin for SNARE-complex binding, thereby dislodging complexin
      from SNARE complexes in a Ca(2+)-dependent manner. Physiologically, increasing
      the local concentration of complexin selectively impairs fast Ca(2+)-triggered
      exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that
      Ca(2+)-induced displacement of complexins from SNARE complexes triggers fast
      exocytosis accounts for the loss-of-function and gain-of-function phenotypes of
      complexins and provides a molecular explanation for the high speed and
      synchronicity of fast Ca(2+)-triggered neurotransmitter release.

PMID- 16990141
TI  - A pattern-based method for the identification of MicroRNA binding sites and their
      corresponding heteroduplexes.
AB  - We present rna22, a method for identifying microRNA binding sites and their
      corresponding heteroduplexes. Rna22 does not rely upon cross-species
      conservation, is resilient to noise, and, unlike previous methods, it first finds
      putative microRNA binding sites in the sequence of interest, then identifies the
      targeting microRNA. Computationally, we show that rna22 identifies most of the
      currently known heteroduplexes. Experimentally, with luciferase assays, we
      demonstrate average repressions of 30% or more for 168 of 226 tested targets. The
      analysis suggests that some microRNAs may have as many as a few thousand targets,
      and that between 74% and 92% of the gene transcripts in four model genomes are
      likely under microRNA control through their untranslated and amino acid coding
      regions. We also extended the method's key idea to a low-error microRNA-precursor
      discovery scheme; our studies suggest that the number of microRNA precursors in
      mammalian genomes likely ranges in the tens of thousands.

PMID- 16990145
TI  - The effect of a live vaccine on the horizontal transmission of Mycoplasma
      gallisepticum.
AB  - The effect of a live Mycoplasma gallisepticum vaccine on the horizontal
      transmission of this Mycoplasma species was quantified in an experimental animal
      transmission model in specific pathogen free White Layers. Two identical trials
      were performed, each consisting of two experimental groups and one control group.
      The experimental groups each consisted of 20 birds 21 weeks of age, which were
      housed following a pair-wise design. One group was vaccinated twice with a
      commercially available live attenuated M. gallisepticum vaccine, while the other
      group was not vaccinated. Each pair of the experimental group consisted of a
      challenged chicken (10(4) colony-forming units intratracheally) and a susceptible
      in-contact bird. The control group consisted of 10 twice-vaccinated birds housed
      in pairs and five individually housed non-vaccinated birds. The infection was
      monitored by serology, culture and quantitative polymerase chain reaction. The
      vaccine strain and the challenge strain were distinguished by a specific
      polymerase chain reaction and by random amplified polymorphic DNA analysis. In
      both experiments, all non-vaccinated challenged chickens and their in-contact
      'partners' became infected with M. gallisepticum. In the vaccinated challenged
      and corresponding in-contact birds, a total of 19 and 13 chickens, respectively,
      became infected with M. gallisepticum. Analysis of the M. gallisepticum shedding
      patterns showed a significant effect of vaccination on the shedding levels of the
      vaccinated in-contact chickens. Moreover, the Cox Proportional Hazard analysis
      indicated that the rate of M. gallisepticum transmission from challenged to in
      contact birds in the vaccinated group was 0.356 times that of the non-vaccinated
      group. In addition, the overall estimate of R (the average number of secondary
      cases infected by one typical infectious case) of the vaccinated group (R = 4.3,
      95% confidence interval = 1.6 to 49.9) was significantly lower than that of the
      non-vaccinated group (R = infinity, 95% confidence interval = 9.9 to infinity).
      However, the overall estimate of R in the vaccinated group still exceeded 1,
      which indicates that the effect of the vaccination on the horizontal transmission
      M. gallisepticum is insufficient to stop its spread under these experimental
      conditions.

PMID- 16990146
TI  - Association between gizzard lesions and increased caecal Clostridium perfringens
      counts in broiler chickens.
AB  - The aim of this study was to investigate the relationship between mucosal gizzard
      lesions and caecal Clostridium perfringens counts. Gross pathological changes in
      the gizzard and small intestine, and caecal C. perfringens counts from 1217 meat
      type chickens were recorded during the course of six experiments and were
      statistically analysed. C. perfringens counts increased significantly (P < 0.001)
      with the severity of mucosal gizzard lesions. Mucosal gizzard lesions were more
      prevalent than necrotic enteritis. Correcting for the pen and necrotic enteritis
      within experiment, mucosal gizzard lesions explained 31.8% of the variation in C.
      perfringens counts. Mucosal gizzard lesions and age together explained 59.1% of
      the variation in C. perfringens counts. The mean ages of birds with moderate and
      severe mucosal gizzard lesions were 1.7 and 0.8 days lower than the mean age of
      birds with necrotic enteritis, respectively. The association between mucosal
      gizzard lesions and high C. perfringens counts might be of importance when
      attempting to improve production efficiency, health and the welfare of the
      chickens.

PMID- 16990147
TI  - Fatty acids and coccidiosis: effects of dietary supplementation with different
      oils on coccidiosis in chickens.
AB  - This study was undertaken to investigate the effects of dietary oils on
      coccidiosis of chickens infected with Eimeria tenella. Five hundred and four 1
      day-old male Arbor Acres chicks were randomly assigned to seven groups. Seven
      diets were supplemented with poultry oil at 25 and 45 g/kg, corn oil at 25 and 45
      g/kg, fish oil at 25 and 45 g/kg, and without oils, respectively, from 1 to 42
      days of age. Chickens were inoculated by gavage with 3 x 10(5) sporulated oocysts
      at 21 days of age. Diets supplemented with oils at 45 g/kg resulted in higher
      body weight gain than with oils at 25 g/kg or without oils. The packed cell
      volume in chicks fed with diets supplemented with poultry oil was lower than that
      in chicks fed with diets supplemented with fish oil, corn oil and without oil.
      Chickens fed with diets supplemented with poultry oil had higher mortality than
      that of chickens fed with diets without oil. At 7 days post infection, the
      chickens consuming fish or corn oil diets had lower levels of plasma carotenoids
      than those fed with poultry oil supplement or without oils. Fish oil
      supplementation increased serum interleukin-6 levels in chickens compared with
      poultry oil at 25 and 45 g/kg and corn oil at 25 g/kg. Fish oil or corn oil
      enhanced secretory IgA levels in the lumen of the caecum, and oil supplementation
      tended to decrease serum IgG levels. In conclusion, the diets supplemented with
      saturated fatty acids aggravated mortality in chickens infected with E. tenella.
      The deleterious effects on coccidiosis of the diets supplemented with poultry
      oils might be related to the decreased levels of caecal E. tenella antigen
      binding-specific secretory IgA or serum IgG.

PMID- 16990148
TI  - Molecular epizootiology of avian infectious bronchitis in Russia.
AB  - Molecular characterization of infectious bronchitis viruses (IBVs) isolated
      between 1998 and 2002 from chickens in Russia was performed. More than 250 field
      samples were tested by reverse transcriptase-polymerase chain reaction using two
      sets of primers corresponding to the most conserved 3'-untranslated region and
      the most variable S1 gene region of the viral genome. Ninety-one IBV isolates
      were characterized by phylogenetic analysis of the S1 gene hypervariable region
      comprising 136 to 558 nucleotides. The major group of isolates (38 viruses)
      showed very close sequence relationship with strains of the Massachusetts
      genotype circulating in Russia since the early 1970s. The analysed region of the
      other 22 Russian IBVs was similar (from 89 to 98% identity) to that from the
      strains of European genotypes including D274 (nine isolates), 793/B (10
      isolates), and B1648, 624/I and Italy-02 (one isolate in each group). Two
      isolates from very distant geographic locations in Russia (Far East and the
      European part) clustered together with Chinese strains of QXIBV genotype. None of
      the remaining 27 Russian isolates showed a close sequence relationship with known
      IBV strains available in sequence databases. The majority of these variant
      viruses clustered into the six novel Russian genotypes, often correlating with
      their geographic location. The remaining five of them were placed outside these
      unique groups, also representing new genotypes. These data for the first time
      demonstrated the high genetic diversity of IBV isolates circulating in Russia.

PMID- 16990149
TI  - Infectious bronchitis virus: S1 gene characteristics of vaccines used in China
      and efficacy of vaccination against heterologous strains from China.
AB  - The entire S1 protein genes of eight infectious bronchitis (IB) vaccine strains
      used in China were compared with those of the IB virus isolates present in the
      field in China. The nucleotide and amino acid similarities between the eight IB
      vaccine strains and the field strain, tl/CH/LDT3/03, which was isolated from a
      teal (Anas sp.), were not more than 81.1% and 79.2%, respectively. Phylogenetic
      analysis based on the S1 genes showed that the vaccines and field strains
      belonged to different clusters and showed larger evolutionary distances, and
      indicated that they were of different genotypes. Four out of the eight vaccines,
      in addition to the Massachusetts type vaccine H120, were used for protection
      tests against challenge by the IB virus isolate tl/CH/LDT3/03. This revealed that
      each of the five IB vaccines induced poor protection against the teal isolate, as
      assessed by respiratory protection, clinical signs and mortality, indicating the
      necessity of developing vaccines from local strains for IB control in China.

PMID- 16990150
TI  - Isolation and characterization of an H10N7 avian influenza virus from poultry
      carcasses smuggled from China into Italy.
AB  - Intensified official veterinary controls on warehouses supplying Chinese
      retailers resulted in the seizure of smuggled poultry products. Frozen and vacuum
      packed frozen raw duck and chicken carcasses, and anatomic parts (legs) of these
      species, were collected and processed for laboratory investigations aiming at the
      detection of avian influenza virus. Real-time reverse transcription-polymerase
      chain reaction (RRT-PCR) targeting the M gene, performed on the lung and trachea
      from duck and chicken carcasses, yielded positive results. Virus isolation
      attempts in specific pathogen free embryonated eggs yielded an H10N7 virus from
      the duck carcass. The isolate had an intravenous pathogenicity index of 0.0, and
      phylogenetic analysis revealed a nucleotide homology of 97 and 96% with virus
      A/duck/Zhejiang/52/2000 (H5N1) for the PB2 and NS genes, respectively. The
      results of this study indicate that low-pathogenicity avian influenza viruses may
      be introduced into a country through trade of carcasses regardless of the non
      systemic nature of this disease. The export ban applied to countries affected by
      the H5N1 epidemic may result in increased smuggling of poultry products, which
      remains one of the means by which influenza viruses can cross-national
      boundaries. Increased surveillance at borders and at a national level is
      recommended.

PMID- 16990151
TI  - Avian hepatitis E virus in an outbreak of hepatitis--splenomegaly syndrome and
      fatty liver haemorrhage syndrome in two flaxseed-fed layer flocks in Ontario.
AB  - Two commercial layer chicken flocks that were fed a flax-based diet beginning at
      28 weeks of age for the production of omega-3 fatty-acid-enriched eggs
      experienced increased mortality when the birds reached 37 weeks. The average
      weekly mortality was 0.34% over a 20-week period, with peak mortality of 0.9% for
      1 week. Reduced feed consumption, reduced body weight gain and poor peak
      production were noticed prior to the onset of increased mortality. A total of 245
      birds were necropsied and 78% of these had lesions in the liver and spleen, with
      44% of those necropsied having changes consistent with hepatitis-splenomegaly
      syndrome, with lesions ranging from acute periportal lymphoplasmacytic hepatitis
      to chronic severe cholangiohepatitis with haemorrhage, vasculitis and
      amyloidosis. A total of 11% of the birds had lesions typical of fatty liver
      haemorrhagic syndrome, and 22% had lesions found in both hepatitis-splenomegaly
      syndrome and fatty liver haemorrhagic syndrome. No significant bacteria or
      viruses were recovered from samples of the liver/bile or spleen but 11 of 21 bile
      samples contained avian hepatitis E virus RNA detectable with a reverse
      transcriptase-polymerase chain reaction assay. Comparative sequence analysis
      found identities of 82 to 92% and 78 to 80% between the helicase and capsid
      protein genes, respectively, of the virus detected in this outbreak and those of
      other avian hepatitis E virus isolates, suggesting extensive genetic
      heterogeneity in avian hepatitis E viruses in Ontario flocks.

PMID- 16990154
TI  - Ethics in research: why and how?

PMID- 16990155
TI  - A randomized trial of lifestyle intervention in primary healthcare for the
      modification of cardiovascular risk factors.
AB  - AIMS: To evaluate the effects of a lifestyle intervention programme in primary
      healthcare, targeted to patients with moderate to high risk of cardiovascular
      disease in terms of cardiovascular risk factors, physical activity, and quality
      of life. METHOD: Randomized controlled trial with one-year follow-up, carried out
      in a primary healthcare centre in Northern Sweden. A total of 151 middle-aged men
      and women, with hypertension, dyslipidemia, type 2 diabetes, or obesity were
      enrolled. The subjects were randomized to either the intervention (n = 75) or the
      control group (n = 76). A total of 123 subjects completed the one-year follow-up.
      INTERVENTIONS: Exercise: supervised endurance and circuit training in groups
      three times a week for three months. Diet: five group sessions of diet
      counselling with a dietitian. Follow- up meetings with a physiotherapist were
      conducted monthly thereafter. Primary outcomes were changes in anthropometry,
      maximal oxygen uptake, health-related quality of life, and self-reported physical
      activity. The secondary outcomes were changes in blood pressure and metabolic
      variables. RESULTS: After one year the intervention group significantly increased
      maximal oxygen uptake, physical activity, and quality of life and significantly
      decreased body weight, waist and hip circumference, body mass index, waist-hip
      ratio, systolic and diastolic blood pressure, triglycerides, and glycosylated
      haemoglobin. There were significant differences between groups, mean changes (and
      their 95% confidence intervals, CI) in waist circumference -1.9 cm (-2.80 to 
      0.90; p<0.001), in waist-hip ratio -0.01 (-.02 to -0.004; p<0.01) and in
      diastolic blood pressure -2.3 mmHg (-4.04 to -0.51; p<0.05). CONCLUSION: A
      prevention programme in primary healthcare with a focus on physical activity and
      diet counselling followed by structured follow-up meetings can favourably
      influence several risk factors for cardiovascular diseases and quality of life in
      high-risk subjects for at least one year.

PMID- 16990156
TI  - Income-related inequality in utilization of health services in Denmark: evidence
      from Funen County.
AB  - AIMS: To examine income-related inequity in utilization of healthcare services in
      Denmark. METHODS: A health survey of 2,915 respondents in Funen County
      interviewed in 2000 and 2001 on health status and socioeconomic and
      sociodemographic characteristics was merged with various computerized registers
      including inpatient stays, ambulatory visits, contacts in the primary healthcare
      sector, and prescription medicine. The index of horizontal inequity was used to
      estimate the degree of horizontal inequity in utilization of healthcare services
      across income groups, using the indirect method of standardization to control for
      age, gender, and self-assessed health as a proxy for need. The standardization
      method rests on the assumption of equal response behaviour across income groups.
      RESULTS: The least advantaged with respect to income consume a bigger share of
      the health services than the most advantaged with the exception of dental
      treatments where the opposite is true. After standardization for age, gender, and
      health status there is no significant inequity in use of all healthcare services.
      However, when it comes to specific healthcare services the least advantaged have
      a significantly lower share of the medicine consumption and dental treatments
      than expected. CONCLUSION: The index of horizontal inequity suggests that the
      Danish healthcare system is in general equitable. In sectors with a high degree
      of co-payment some horizontal inequity disfavouring the lower income groups
      appears to be present.

PMID- 16990158
TI  - Housing tenure and early retirement for health reasons in Sweden.
AB  - AIMS: To assess the association between housing tenure and early retirement for
      health reasons in Sweden with a view to psychosocial vs. material values of home
      ownership. METHODS: The data come from linked registers that cover all people
      resident in Sweden during 1990-2000. The study population consists of 449,233
      people aged 40-63 years in 1997. Of these, 19,350 retired early for health
      reasons in 1998-99. The remaining 429,883 continued their employment without
      extended sick leave or income decline. None moved during 1990-2000. We calculated
      the odds of early retirement for four forms of juridical relationship to one's
      housing (private owner; part owner in a cooperative; private rental; rental from
      a public housing company), for men and women separately, controlling for age,
      education, employment income, household disposable income, region, foreign birth,
      and housing type. RESULTS: Men in cooperative ownership had lower odds of early
      retirement than those in the three other tenure forms, for which the odds were
      similar. Among women, public and private renters had similar odds of early
      retirement, which were higher than those of women in private or cooperative
      ownership. For both genders, inclusion of housing type in the model after housing
      tenure explained little additional variance. CONCLUSIONS: The odds of early
      retirement for health reasons varied across different housing tenure forms in
      Sweden in 1998-99. The pattern of associations differed as a function of gender.
      Home ownership appears to involve health resources independent of basic socio
      physical factors captured with differences in housing type.

PMID- 16990159
TI  - Low physical activity and mortality in women: baseline lifestyle and health as
      alternative explanations.
AB  - AIMS: The aim of this study was to investigate the association between physical
      activity and mortality in post-menopausal women. In addition, the authors wanted
      to investigate to what extent this association could be attributed to confounding
      from other lifestyle factors, and to reverse causation due to a number of common
      health problems that may inhibit the ability to exercise. METHODS: A total of
      27,734 women aged 51-83 years from the Swedish Mammography Cohort were
      investigated. In 1997 they responded to a detailed questionnaire including
      questions on physical activity, diet, alcohol intake, smoking, and medical
      problems. During follow-up in 1999-2004, 1,232 deaths were identified by linkage
      to the National Population Register. RESULTS: Women with low physical activity
      (35 MET*h/day) had a 3.22 times increased mortality (95% confidence interval (CI)
      = 2.35-4.43) compared with the most active women (>50 MET*h/day). No increased
      risk was seen in women with moderate compared with high physical activity.
      Sedentary women tended to have a less healthy lifestyle and more health problems
      at baseline, e.g. almost 30% of them reported high blood pressure compared with
      less than 20% of active women. Baseline medical problems and lifestyle factors
      such as smoking, diet, and education accounted for 30% of the excess risk seen in
      sedentary women (24% and 6% respectively). CONCLUSIONS: This study indicates that
      even fairly small amounts of activity will reduce mortality in older women.
      However, sedentary women seemed to be a selected group with more medical problems
      and a less healthy lifestyle. The findings indicate that the association between
      physical inactivity and mortality will be overestimated if this is not taken into
      account.

PMID- 16990160
TI  - Diverging trends in the incidence and mortality of stroke during the period 1986
      2002: a study from the stroke register in Kaunas, Lithuania.
AB  - AIMS: The aim of the present study was to explore the longitudinal stroke trends
      in the middle-aged Lithuanian population. METHODS: All stroke events in the
      studied population were ascertained and validated according to the standardized
      criteria outlined by the WHO MONICA Project. The study included all patients aged
      25 to 64 years who experienced a stroke between 1986 and 2002. RESULTS: A flat
      trend was observed in both the incidence and the attack rates of stroke among men
      during the 17-year study period, while among women, the incidence of stroke
      increased by 1.7%/year, and the attack rates by 2.3%/year. The 28-day case
      fatality and mortality rates of stroke decreased significantly in both sexes. The
      decline in case fatality explained 100% of the decline in mortality. Among the
      types of stroke, cerebral infarction contributed most to the decline in the
      mortality in men. In women, the mortality from cerebral infarction and
      intracerebral haemorrhage declined similarly to that from all types of strokes.
      CONCLUSIONS: Findings from our study indicating no positive changes in the
      incidence of stroke but instead an increase among middle-aged women in Kaunas are
      disturbing. These results suggest a need for the intensification of appropriate
      strategies for stroke prevention by the public health officials in Lithuania.

PMID- 16990161
TI  - Prevalent musculoskeletal pain as a correlate of previous exposure to torture.
AB  - AIM: To research possible associations between previous exposure to specific
      torture techniques and prevalent pain in the head and face, back, and feet.
      METHODS: 221 refugees, 193 males and 28 females, previously exposed to torture in
      their home country, were subject to a clinical interview at a rehabilitation
      clinic for torture victims. The interview focused on exposure to torture and
      somatic symptoms prevalent at examination. RESULTS: The mean number of times
      imprisoned was 2.3; the mean number of months imprisoned was 19.7; the mean
      duration from initial imprisonment to final release was 3.7 years; and the mean
      duration from final release to preliminary interview was 8.4 years. The most
      frequent physical torture method reported was beating (92.3%) and the main mental
      torture method was deprivation (84.6%). Pain in the head and face was found to be
      strongly associated with torture against head and face (OR 3.89, 95% CI 1.49
      10.20) and with the cumulative number of physical torture methods exposed to.
      Pain in the back was associated with sexual torture (OR 2.75, 95% CI 1.07-7.12).
      Besides beating of the lower extremities (OR 5.98, 95% CI 2.47-14.48), the
      strongest predictor for pain in the feet was general abuse of the whole body (OR
      5.64, 95% CI 1.93-16.45). CONCLUSION: In spite of many factors being potentially
      co-responsible for prevalent pain, years after the torture took place it presents
      itself as strongly associated with specific loci of pain, with generalized
      effects, and with somatizing.

PMID- 16990162
TI  - Socioeconomic factors, country of birth, and years in Sweden are associated with
      first birth fertility trends during the 1990s: a national cohort study.
AB  - AIMS: Decreasing fertility rates and postponement of first birth are of
      considerable public health concern in many industrialized countries. Previous
      studies suggest that this will increase involuntary childlessness in the
      population. The general aim was to examine the association between
      sociodemographic factors and first birth fertility trends in Sweden during the
      1990s. METHODS: This Swedish national study examined changes in first birth rates
      and mean age at first birth between 1991 and 1992 (n = 452,000) and 1997-98 (n =
      495,756). The impact of socioeconomic factors and years in Sweden on first birth
      fertility was examined among Swedish-born and 19 subgroups of foreign-born women
      aged 20-41 years. Poisson regression was used in the analysis. RESULTS: First
      birth rates decreased and mean age at first birth increased between the two
      periods among the Swedish-born and most foreign-born women. Non-employment and
      low income were associated with decreased first birth fertility, and low
      educational status was associated with slightly increased first birth fertility.
      Interaction tests revealed that, in contrast to Swedish-born women, several
      groups of foreign-born women increased their first birth fertility even if they
      were non-employed or had a low income. Among foreign-born women fewer years in
      Sweden was significantly associated with increased first birth fertility.
      CONCLUSION: Public health information should emphasize that postponement of first
      birth could lead to involuntary childlessness. Health care workers need to
      consider the woman's socioeconomic characteristics, country of birth, and years
      in Sweden when such information is given.

PMID- 16990163
TI  - Sense of coherence and its determinants: a comparative study of the Finnish
      speaking majority and the Swedish-speaking minority in Finland.
AB  - BACKGROUND: Despite similar living conditions among the Finnish-speaking majority
      and the Swedish-speaking minority in Finland, the latter is a more advantaged
      group e.g. in terms of socioeconomic status and health. This study investigated
      (1) the level of sense of coherence (SOC), (2) the structure of generalized
      resistance resources (GRRs), and (3) associations of GRRs with SOC among Finnish-
      and Swedish-speaking Finns. METHODS: The data derived from the Health and Social
      Support (HeSSup) Study. The sample comprised 22,937 Finnish men and women aged 20
      54, including an additional sample from the Swedish-speaking population (n =
      2,967). The response rate was 40%. Ordinary regression analysis was used.
      RESULTS: Swedish-speaking women scored 0.9 (p = 0.005) and men 0.6 (p = 0.05)
      points higher on SOC scale compared with Finnish-speaking respondents. The minor
      difference in the SOC level between the language groups was explained by Finnish
      speakers' worse psychosocial living conditions in childhood and working
      conditions in adulthood. Only one interaction was found: parents' divorce during
      childhood was associated with a significant decrease of SOC scores only for
      Finnish speakers. Otherwise the same GRRs had similar effects on both Finnish-
      and Swedish-speaking men's and women's SOC. CONCLUSION: The only key difference
      between Finnish- and Swedish-speaking Finns concerned the unequal distribution of
      GRRs. An increase in GRRs among Finnish speakers would probably strengthen their
      SOC. However, the slightly stronger level of SOC among Swedish-speaking compared
      with Finnish-speaking Finns is unlikely to explain the possible differences in
      well-being between the two language groups.

PMID- 16990164
TI  - The impact of water supply and sanitation on area differentials in the decline of
      diarrhoeal disease mortality among infants in Stockholm 1878-1925.
AB  - This study analyses the impact of improved water supply and sanitation on the
      level and rate of decline of child diarrhoea mortality in Stockholm 1878-1925.
      Previous studies have failed to demonstrate an effect of improved water supply on
      the risk of diarrhoea mortality at the individual level. Using data on access to
      water and sanitation from a household survey in 1895 and mortality rates and
      sociodemographic information from individual data 1878-1925 to analyse area
      differentials in diarrhoea mortality, it was found that the proportion having
      their own latrine in the household was associated with lower mortality risk in
      1895-1900, while the proportion having water in the household was associated with
      lower diarrhoea mortality risk during the mortality decline until 1925.
      Population effects of improved water and sanitation on diarrhoea mortality may be
      better measured at area level than at individual level.

PMID- 16990165
TI  - Potential self-selection bias in a nested case-control study on indoor
      environmental factors and their association with asthma and allergic symptoms
      among pre-school children.
AB  - Selection bias means a systematic difference between the characteristics of
      selected and non-selected individuals in epidemiological studies. Such bias may
      be introduced if participants select themselves for a study. The present study
      aims at identifying differences in family characteristics, including health,
      building characteristics of the home, and socioeconomic factors between
      participating and non-participating families in a nested case-control study on
      asthma and allergy among children. Information was collected in a baseline
      questionnaire to the parents of 14,077 children aged 1-6 years in a first step.
      In a second step 2,156 of the children were invited to participate in a case
      control study. Of these, 198 cases and 202 controls were finally selected. For
      identifying potential selection bias, information concerning all invited families
      in the case-control study was obtained from the baseline questionnaire. Results
      show that there are several possible biases due to self-selection involved in an
      extensive study on the impact of the home environment on asthma and allergy among
      children. Factors associated with participating were high socioeconomic status of
      the family, more health problems in the case families, and health-related
      lifestyle factors, such as non-smoking parents. The overall conclusion of this
      study is that there are selection biases involved in studies that need close
      cooperation with the families involved. One solution to this problem is
      stratification, i.e. investigating associations between exposures and health in
      the same socioeconomic strata.

PMID- 16990166
TI  - The significance of neighbourhood context to child and adolescent health and well
      being: a systematic review of multilevel studies.
AB  - Growing up in a poor neighbourhood has negative effects on children and
      adolescents. In the literature it has been concluded that the risk of low birth
      weight, childhood injury and abuse, and teenage pregnancy or criminality double
      in poor areas. However, the validity of such studies has been questioned, as they
      have been associated with ecological or individualistic fallacies. Studies using
      multilevel technique might thus contribute important knowledge in this field. The
      present review clarifies the importance of neighbourhood contextual factors in
      child and adolescent health outcomes, through considering only studies using
      multilevel technique. Keyword searching of the Medline, ERIC, PsycInfo,
      Sociological Abstracts, and Social Citation Index databases was performed.
      Original studies using multilevel technique to examine the effect of
      neighbourhood characteristics on child and adolescent health outcomes, and
      focusing on populations in high-income countries were included. Neighbourhood
      socioeconomic status and social climate were shown to have small to moderate
      effects on child health outcomes, i.e. birth weight, injuries, behavioural
      problems, and child maltreatment. On average, 10% of variation in health outcomes
      was explained by neighbourhood determinants, after controlling for important
      individual and family variables. This review demonstrates that interventions in
      underprivileged neighbourhoods can reduce health risks to children, especially in
      families that lack resources. An analysis of methodological fallacies indicates
      that observed effects and effect sizes can be underestimated, and that
      interventions may well have greater impact than this review was able to
      establish.

PMID- 16990167
TI  - Prevalence of low back pain and sickness absence: a "borderline" study in Norway
      and Sweden.
AB  - AIMS: Low back pain (LBP) is a major public health problem in both Norway and
      Sweden. The aim of the study was to estimate the prevalence of LBP and sickness
      absence due to LBP in two neighbouring regions in Norway and Sweden. The two
      areas have similar socioeconomic status, but differ in health benefit systems.
      METHODS: A representative sample of 1,988 adults in Norway and 2,006 in Sweden
      completed questionnaires concerning LBP during 1999 and 2000. For this study only
      individuals in part or full time jobs, (n = 1,158 in Norway and n = 1,129 in
      Sweden) were included. RESULTS: In Norway the lifetime prevalence was 60.7% and
      in Sweden 69.6%, the one-year prevalence was 40.5% and 47.2%, and the point
      prevalence 13.4% and 18.2% respectively. There was a significantly higher risk of
      reporting LBP in Sweden, even after controlling for gender, age, education, and
      physical workload. There was no difference in risk of self-certified short-term
      sickness absence (1-3 days), but it was a 40% lower risk of sickness absence with
      medical sickness certification in Sweden compared with Norway. CONCLUSION: The
      prevalence of LBP was higher in the Swedish area than in the Norwegian. The risk
      of self-certified sickness absence, however, showed no differences and the risk
      of medically certified sickness absence was lower in the Swedish area. This
      contradiction might partly be explained by the economical "disincentives" in the
      Swedish health compensation system.

PMID- 16990168
TI  - Predicting and preventing suicide: do we know enough to do either?
AB  - In population studies, many risk factors are associated with suicide completion.
      Yet we cannot accurately predict whether any individual patient will die by
      suicide. Completers are a distinct population from attempters and do not
      necessarily present for treatment by mental health professionals. Research on
      suicide prevention has yielded some promising findings but has not shown that
      interventions produce definitive results. The strongest evidence for successful
      prevention derives from reducing access to means. A population-based strategy may
      be more effective than a high-risk strategy focusing on patients with suicidal
      ideas or attempts. Much more research is needed before developing effective
      suicide prevention programs.

PMID- 16990169
TI  - Alcohol dependence and suicidal behavior: from research to clinical challenges.
AB  - Epidemiological and clinical data suggest high rates of suicidal behavior in
      alcohol-dependent individuals. Suicide attempters are likely to be young, to be
      single or separated, and to have made prior attempts. They differ from non
      attempters by higher levels of impulsive aggression, drug use, and psychiatric
      comorbidity, particularly personality and depressive disorders. Treatment
      seeking, alcohol-dependent individuals often present with multiple risk factors.
      Early recognition of suicidal behavior is hindered, however, by insufficient data
      regarding the acute phenomenology of imminent risk. Similarly, little research is
      available to guide intervention efforts. Initial trials support the use of
      fluoxetine for the treatment of suicidal, alcohol-dependent persons with comorbid
      depressive disorders. Future studies may clarify the relative efficacy of various
      psychotherapeutic and pharmacological approaches to treating these patients.

PMID- 16990170
TI  - Borderline personality disorder, stigma, and treatment implications.
AB  - Borderline personality disorder (BPD) is often viewed in negative terms by mental
      health practitioners and the public. The disorder may have a stigma associated
      with it that goes beyond those associated with other mental illnesses. The stigma
      associated with BPD may affect how practitioners tolerate the actions, thoughts,
      and emotional reactions of these individuals. It may also lead to minimizing
      symptoms and overlooking strengths. In society, people tend to distance
      themselves from stigmatized populations, and there is evidence that some
      clinicians may emotionally distance themselves from individuals with BPD. This
      distancing may be especially problematic in treating patients with BPD; in
      addition to being unusually sensitive to rejection and abandonment, they may
      react negatively (e.g., by harming themselves or withdrawing from treatment) if
      they perceive such distancing and rejection. Clinicians' reactivity may be self
      protective in response to actual behavior associated with the pathology. As a
      consequence, however, the very behaviors that make it difficult to work with
      these individuals contribute to the stigma of BPD. In a dialectical relationship,
      that stigma can influence the clinician's reactivity, thereby exacerbating those
      same negative behaviors. The result is a self-fulfilling prophecy and a cycle of
      stigmatization to which both patient and therapist contribute. The extent to
      which therapist distancing is influenced by stigma is an important question that
      highlights the possibility that the stigma associated with BPD can have an
      independent contribution to poor outcome with this population. A final issue
      concerns the available means for identifying and limiting the impact of
      stigmatization on the treatment of individuals with BPD.

PMID- 16990171
TI  - A psychotherapy dominated by separation, termination, and death.

PMID- 16990172
TI  - The role of personal psychodynamic psychotherapy in becoming a competent
      psychiatrist.

PMID- 16990173
TI  - Assessing food safety and associated food handling practices in street food
      vending.
AB  - Street vendors in the city of Bloemfontein were investigated in order to assess
      the microbiological quality of the food being sold as well as the level of
      hygiene conditions under which these food stalls operate. The food samples which
      were collected included beef, chicken and gravy, while surface samples were taken
      from the food preparation tables and the hands of the vendors. A structured
      questionnaire and checklist were used in interviews to determine the status of
      the vending sites and associated food handling practices. The overall
      microbiological quality of the foods served by the street vendors was found to be
      within acceptable safety limits, although the presence of specific microorganisms
      such as Escherichia coli, Staphylococcus aureus, Salmonella and yeasts is
      indicative of a degree of ignorance on the part of the food handlers towards
      proper hygienic practices.

PMID- 16990174
TI  - Estimation of benchmark doses for urinary cadmium based on beta2-microglobulin
      excretion in cadmium-polluted regions of the Kakehashi River basin, Japan.
AB  - A benchmark dose low (BMDL) is used as a replacement for the no observed adverse
      effect level. The threshold levels of urinary cadmium (Cd) as BMDL were estimated
      using data from the Kakehashi River basin. The target population (>or=50 years)
      comprised 3178 and 294 participants inhabiting Cd-polluted and non-polluted
      areas, respectively. Cut-off values for beta2-MG-uria were defined as the 84 and
      95% upper limit values calculated from control subjects, and 1000 microg/l or
      microg/g cr of beta2-MG. Using these cut-off values, the BMDL at which the excess
      risk is 0.05 was determined to be 2.9 - 4.0 microg/g cr (males) and 1.5 - 3.6
      microg/g cr (females). The present study demonstrated that a BMD approach is
      useful to estimate the threshold level of urinary Cd in Cd-exposed subjects and
      people living in general environment without any known Cd-pollution since a BMD
      approach does not need abnormality rates of urinary findings in the controls.

PMID- 16990176
TI  - Risk of giardiasis associated with water supply in an endemic context.
AB  - Consumption of untreated, inadequately treated or simply chlorinated water has
      been the source of a number of giardiasis epidemics. The aim of this study was to
      verify if water supply is associated with giardiasis in an endemic context. We
      conducted a case-control study that included 139 cases and 417 control subjects.
      To assess risk associated to water consumption, we calculated odds ratios (OR)
      using "source of water" and "presence and type of filtration" as criteria. A
      logistic regression model was used to control other risk factors. In children
      aged 1 - 13, the only significant risk factor was the consumption of at-risk tap
      water (i.e., filtered or unfiltered surface water or unfiltered shallow well
      water; OR = 6.13). In people aged 14 - 64, the consumption of this water was not
      a risk factor for the disease. The divergence in results between age groups could
      be explained by acquired immunity.

PMID- 16990175
TI  - Pesticide use and safety practices among Greek tobacco farmers: a survey.
AB  - An attempt was made to explore knowledge, attitudes, and practices towards safety
      issues of pesticide handling among tobacco farmers of the rural area of Pieria in
      northern Greece. From the 310 survey questionnaires that were mailed out, 223
      were received fully and correctly completed resulting in a quite satisfactory
      response rate of 72%. A large majority of the farmers (96%) viewed pesticides as
      a guarantee for high tobacco yields and high product quality. Almost all farmers
      (99%) thought that pesticides can have serious adverse effects on users' health.
      Skin contact was recognized as the most common route of exposure during pesticide
      use (58%). Despite awareness of potential health risks by pesticide handling, a
      significant proportion of the farmers (46%) reported not using any special
      protective equipment when spraying pesticides. From those who reported that they
      use protective equipment, most stated that they normally use a hat (47%) and
      boots (63%). Only few farmers reported using a face mask (3%), gloves (8%), and
      coveralls (7%) on a regular basis. The reasons for not using protective equipment
      during pesticide handling were that protective equipment is uncomfortable (68%),
      too expensive to buy (17%), time-consuming to use (8%), not available when needed
      (6%), and not necessary for each case (2%). A large majority of the farmers (84%)
      said that they replace work clothing when it wears out and a considerable part
      (48%) stated that they wash work clothing after several uses. Although farmers'
      knowledge of potential hazards by pesticide use was high, the reported safety
      measures were poor. Continuous emphasis on the basic safety precautions required
      when using pesticides and on the importance of protective equipment is essential
      for changing wrong habits of farmers which can be hazardous for their health.

PMID- 16990177
TI  - Airborne total gaseous mercury and exposure in a Venezuelan mining area.
AB  - This paper presents a short-term monitoring study of total gaseous mercury (TGM)
      in air, and exposure to airborne mercury. The evaluation was carried out in
      polluted mining sites (El Callao, Venezuela), where for decades mercury has been
      used in diverse stages of gold mining activities. The contamination is mainly due
      to emission of Hg0 during gold amalgamation and burning, which can cause direct
      human health risks. Total gaseous mercury (TGM) in air was analysed in mill,
      jewellery and indoor house sites, and at different heights (height profiles near
      the surface) at polluted and not polluted sites. Mercury concentration in air was
      measured with a portable mercury analyser (Lumex Ra-915+). Time weighted average
      mercury (TWA) was calculated for the evaluation of mercury exposure. TWA values
      ranged between 0.28 microg m(-3) and >100 microg m(-3). These measurements were
      done during sunny and dry days. In the case of mills and gold workshops, the
      values were over the limit recommended by the World Health Organization to
      exposure (25 microg m(-3)) and NIOSH limit (50 microg m(-3)). Indoors in a house,
      the air Hg average value was 2.58 microg m(-3) exceeding EPA (0.3 microg m(-3))
      and ATSDR (1 microg m(-3)) guidelines. The mercury concentration at different
      height profiles, varied between 1766 microg m(-3) and 0.014 microg m(-3). Mercury
      height profiles were described by a power function model of the form c(Hg) = ah(
      b), where a parameter describes the magnitude of Hg emission. For polluted sites
      there was a significant correlation between a and Hg in soil or Hg emission from
      soil to air, while b is only significantly correlated with air temperature. An
      air and soil mercury measurement transect was carried out at a mill site up to a
      distance of 1000 m, and it was observed that the air mercury concentration
      decreases with increasing distance from the mill site, and inversely to Hg soil
      content.

PMID- 16990178
TI  - Ribotype diversity of Listeria monocytogenes isolates from two salmon processing
      plants in Norway.
AB  - The purpose of this study was to use automated ribotyping procedure to track
      Listeria monocytogenes transmission in the cold smoked fish production chain and
      to characterize L. monocytogenes subtypes associated with the salmon processing
      industry. A total of 104 isolates, which had previously been obtained from a raw
      fish slaughter and processing plant (plant B) and an adjacent, downstream, salmon
      smoking operation (plant A), were characterized. These isolates had been obtained
      through a longitudinal study on Listeria presence, which covered a 31-week
      period, in both plants. Isolates had been obtained from samples taken from
      different machinery used throughout the production process. In addition, six
      isolates obtained from products produced in plant A two years after the initial
      study were included, so that a total of 110 isolates were characterized.
      Automated ribotyping was performed using both the restriction enzymes EcoRI and
      PvuII to increase the discriminatory power. The 110 L. monocytogenes isolates
      could be divided into 11 EcoRI ribotypes; PvuII ribotype data yielded multiple
      subtypes within 7 EcoRI ribotypes for a total of 21 subtypes based on both EcoRI
      and PvuII ribotyping. A total of three EcoRI ribotypes (DUP-1023C, DUP-1045B, and
      DUP-1053E) were isolated at multiple sampling times from both plants. In
      addition, one subtype (DUP-1053B) was isolated at multiple sampling times in only
      plant A, the salmon smoking operation. These data not only support that L.
      monocytogenes can persist throughout the salmon production system, but also
      showed that L. monocytogenes may be transmitted between slaughter and smoking
      operations or may be unique to smoking operations. While the majority of subtypes
      isolated have been rarely or never linked to human listeriosis cases, some
      subtypes have previously caused human listeriosis outbreaks and cases. Molecular
      subtyping thus is critical to identify L. monocytogenes transmission and niches
      in order to allow design and implementation of control strategies at the
      appropriate stage of production and in order to reduce the prevalence of L.
      monocytogenes linked to human disease.

PMID- 16990179
TI  - Bacterial contamination of drinking water and the economic burden of illnesses
      for the Nepalese households.
AB  - A household survey was conducted to determine the number of working days lost and
      household medical expenditure (ME) due to six water-borne diseases in the Terai
      region of Nepal. Drinking water sources of each household were analysed for total
      coliforms (TC). The study found 61% of the household water sources were
      contaminated with TC at the time of sampling. Number of days lost due to water
      borne diseases was 8 days for TC-negative households and 10 days for TC-positive
      households per year. The average annual household medical expenditure was NR 459
      for TC-negative households, and NR 789 for TC-positive households (p = 0.02 at
      proportional to = 0.05). Regression result showed that the presence of TC in the
      drinking water sources, number of children in the household and income of the
      household significantly determined ME.

PMID- 16990180
TI  - Avascular necrosis of the femoral head: vascular hypotheses.
AB  - Vascular hypotheses provide compelling pathogenic mechanisms for the etiology of
      avascular necrosis of the femoral head (ANFH). A decrease in local blood flow of
      the femoral head has been postulated to be the cause of the disease. Several
      studies in human and animal models of ANFH have shown microvascular thrombosis.
      Endothelial cell damage could be followed by abnormal blood coagulation and
      thrombus formation with any resulting degeneration distal to the site of vascular
      occlusion. Other studies suggest that thrombophilia, particularly impaired
      fibrinolysis, plays a potential role in thrombus formation in ANFH. Reduction in
      shear stress due to decreased blood flow could lead to apoptosis of endothelial
      cells, which can ultimately contribute to plaque erosion and thrombus formation.
      Dysregulation of endothelial cell activating factors and stimulators of
      angiogenesis or repair processes could also affect the progression and outcome of
      ANFH. Likewise, regional endothelium dysfunction (RED), referred to as a
      potential defect in endothelial cells located in the feeding vessels of the
      femoral head itself, may also have a crucial role in the pathogenesis of ANFH.
      Molecular gene analysis of regional endothelial cells could also help to
      determine potential pathways important in the pathogenesis of ANFH.

PMID- 16990181
TI  - Concanavalin A, but not glycated albumin, increases subendothelial deposition of
      von Willebrand factor in vitro.
AB  - Diabetes is associated with augmentation of prothrombogenic von Willebrand factor
      (vWF) content in plasma. Earlier, the author and colleagues have shown that high
      glucose and insulin do not appreciably influence deposition of vWF into the
      subendothelial extracellular matrix (SECM) produced by cultured human umbilical
      vein endothelial cells (HUVECs). In the present work, the author used this model
      to test the effects of nonenzymatically glycated albumin (Glyc-HSA) and two
      lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), on vWF deposition
      into the SECM. First-passage HUVECs were seeded into gelatin-coated 96-well
      plates and cultured for 6 to 7 days. HSA or Glyc-HSA (at concentrations 25, 50,
      and 100 microg/mL), and WGA or ConA (4, 8, and 16 microg/mL) were added 3 h after
      seeding. Cell viability was tested by the MTT method. To determine vWF contents
      in the SECM, HUVECs were detached by treatment with NH4OH and the residual
      material was used as a solid phase in an enzyme-linked immunosorbent assay
      (ELISA)-like assay with primary (anti-vWF) and secondary (peroxidase-conjugated)
      antibodies. Addition of Glyc-HSA did not essentially influence VWF contents in
      the SECM (A490 was 0.226 versus 0.268 at 0 and 100 microg/mL, respectively; p >
      .05, n = 16). Cultivation in the presence of WGA led to the deterioration of cell
      viability, which was accompanied by a significant decrease of vWF in the SECM
      (0.248 versus 0.128 at 0 and 16 microg/mL, respectively; p < .001, n = 16). ConA
      did not influence viability of HUVECs, but this lectin at all concentrations
      consistently increased the deposition of vWF (up to 164% relative to control, p
      <.001; n = 16). These data indicate that endothelial carbohydrate determinants
      and corresponding ligands (namely, mannose-specific lectins) may be involved in
      the regulation of production and deposition of vWF.

PMID- 16990183
TI  - Activation of protein kinase A improves vascular endothelial dysfunction.
AB  - The study has been designed to investigate the effect of 8-Br-cAMP, an activator
      of protein kinase A (PKA), 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 >200 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. The expression of mRNA for
      p22phox and endothelial nitric oxide synthase (eNOS) was assessed by using
      reverse transcriptase-polymerase chain reaction (TBARS) (RT-PCR). Serum
      thiobarbituric acid-reactive substances (TBARS) concentration and aortic
      superoxide anion concentration were estimated to assess oxidative stress. 8-Br
      cAMP (5 mg kg-1, i.p.) or atorvastatin (30 mg kg-1, p.o.) prevented diabetes
      mellitus- and hyperhomocysteinemia-induced attenuation of acetylcholine-induced
      endothelium-dependent relaxation, impairment of vascular endothelial lining,
      decrease in expression of mRNA for eNOS, serum nitrite/nitrate concentration, and
      increase in expression of mRNA for p22phox, superoxide anion, and serum TBARS.
      The ameliorative effect of 8-Br-cAMP was prevented by N omega-nitro-L-arginine
      methyl ester (L-NAME) (25 mg kg-1, i.p.) and glibenclamide (5 mg kg-1, i.p.).
      Therefore, it may be concluded that 8-Br-cAMP-induced activation of PKA may
      improve vascular endothelial dysfunction.

PMID- 16990182
TI  - Inhibition of endothelial cell proliferation, in vitro angiogenesis, and the down
      regulation of cell adhesion-related genes by genistein. Combined with a cDNA
      microarray analysis.
AB  - Antiangiogenesis is presently one of the powerful strategies for treating cancer,
      and endothelial cells play a pivotal role in the process of angiogenesis.
      Genistein, a tyrosine kinase inhibitor, a major isoflavone plentiful in soybeans,
      is known to inhibit both tumor growth and angiogenesis. However, the precise
      molecular mechanism(s) by which genistein affects endothelial cells has yet to be
      elucidated. In the present study, a cDNA microarray was performed to investigate
      the targeted genes of human umbilical vein endothelial cells (HUVECs) affected by
      10 microM genistein. As a result, a total of 256 genes showed an altered
      expression of more than twofold. Among them were the genes related to cell
      proliferation, adhesion, transcription, translation, metabolism, cytoskeleton,
      apoptosis, kinases, and functionally unknown. The down-regulation of mRNA or the
      protein expression of cell adhesion-related genes, including VE-cadherin, gap
      junction protein alpha 1 (connexin 43), integrin alpha V, and multimerin, were
      confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) or by
      immunofluorescence staining. The impaired cell-cell adhesion by genistein was
      also observed by electron microscopy. In addition, the antiangiogenesis role of
      genistein was confirmed on Matrigel using inverted microscopy and electron
      microscopy. In conclusion, genistein affects endothelial cells as a negative
      mediator of proliferation and angiogenesis in vitro, partially by down-regulating
      cell adhesion-related genes and impairing cell adhesions.

PMID- 16990184
TI  - High efficiency and long-term foreign gene expression in cultured liver
      sinusoidal endothelial cells by retroviral transduction.
AB  - The liver sinusoidal endothelial cells (LSECs) constitute a very specialized
      endothelium. Due to their multiple functions and privileged location in the
      liver, these cells constitute an excellent target for gene therapy. In this work,
      the authors investigate the efficiency of retroviral gene transduction as a
      method for in vitro gene delivery into murine LSECs. Gene transduction into
      murine LSECs was performed using the PCMMP-eGFP/pIK-MLVgp retrovirus pseudotyped
      with the vesicular stomatitis virus G glycoprotein (VSV-g), containing eGFP as a
      reporter gene. Retroviral transduction resulted in a high efficiency of gene
      transfer (99%) and stable expression of eGFP in LSECs. The retroviral
      transduction protocol did not affect the morphology or expression of endothelial
      cell markers or the biological functions of LSECs. The authors have developed
      conditions for high-efficiency and stable retroviral gene transduction of LSECs.
      These results raise the possibility of liver gene therapy using LSECs as vehicle
      for the delivery of therapeutic proteins by means of retroviral vectors.

PMID- 16990185
TI  - Role of CD7 expressed in lung microvascular endothelial cells as Fc receptor for
      immunoglobulin M.
AB  - Immunoglobulins (Igs) against anti-human white blood cells are putative
      contributors to the development of transfusion-related adverse effects,
      particularly transfusion-related acute lung injury (TRALI). Studies of Igs that
      are considered to be implicated in transfusion-related adverse effects have
      mainly focused on immunoglobulin G (IgG) class antibodies (Abs). In the authors'
      previous in vitro study, the association of polymorphonuclear neutrophils (PMNs)
      and lung microvascular endothelial (LME) cells was up-regulated in the presence
      of normal human serum-derived IgMs, when F(ab')2 fragments of IgMs were specific
      to low-affinity Fc receptors (FcR) for IgG, namely, Fcgamma R III (CD16) and
      Fcgamma RII (CD32). In this study, the authors found that CD7 antigen notably
      expresses in LME cells and that it acts as an Fc receptor for IgM in LME cells.

PMID- 16990188
TI  - Hydroxocobalamin for acute cyanide poisoning: new data from preclinical and
      clinical studies; new results from the prehospital emergency setting.

PMID- 16990189
TI  - Efficacy of hydroxocobalamin for the treatment of acute cyanide poisoning in
      adult beagle dogs.
AB  - INTRODUCTION: The efficacy of hydroxocobalamin for acute cyanide poisoning was
      compared with that of saline vehicle in dogs. METHODS: Anesthetized adult beagle
      dogs were administered potassium cyanide (0.4 mg/kg/min, IV) until 3 min after
      the onset of apnea. Hydroxocobalamin (75 mg/kg [n = 19] or 150 mg/kg [n = 18],
      IV) or saline vehicle [n = 17] was then infused over 7.5 min while animals were
      ventilated with 100% oxygen, which was stopped after 15 min. RESULTS: In vehicle
      treated animals cyanide produced deterioration that culminated in a moribund
      state requiring euthanasia within 4 h in 10 of 17 animals and in neurological
      deficits necessitating euthanasia within 2-4 d in an additional 4 animals
      (mortality rate 82%). Survival through 14 d was observed in 15 of 19 animals
      administered hydroxocobalamin 75 mg/kg (mortality rate 21%), and 18 of 18
      administered hydroxocobalamin 150 mg/kg (mortality rate 0%). CONCLUSION:
      Hydroxocobalamin reversed cyanide toxicity and reduced mortality in a canine
      model.

PMID- 16990190
TI  - Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo
      controlled study.
AB  - INTRODUCTION: This randomized, double-blind, placebo-controlled, ascending-dose
      study was conducted in healthy volunteers to evaluate the safety of the
      investigational cyanide antidote hydroxocobalamin. METHODS: Four ascending dosing
      groups received intravenous doses of 2.5, 5, 7.5 or 10 g hydroxocobalamin over
      7.5 to 30 minutes at a constant infusion rate. Volunteers (n = 136) randomized
      3:1 to receive hydroxocobalamin or placebo underwent a 4-day in-house observation
      after infusion on Day 1 and follow-up visits on Days 8, 15, and 28. RESULTS: The
      most common drug-related adverse events were asymptomatic and self-limiting
      chromaturia and reddening of the skin, which are attributed to the red color of
      hydroxocobalamin. Other adverse events included pustular/papular rash, headache,
      erythema at the injection site, decrease in lymphocyte percentage, nausea,
      pruritus, chest discomfort, and dysphagia. Hydroxocobalamin was associated with
      an increase in blood pressure in some volunteers. Blood pressure changes peaked
      toward the end of hydroxocobalamin infusion and typically returned to baseline
      levels by 4 hours postinfusion. Maximum mean changes from baseline in systolic
      blood pressure ranged from 22.6 to 27.0 mmHg across hydroxocobalamin doses
      compared with 0.2 to 6.7 mmHg in the corresponding placebo groups. Maximum mean
      change from baseline in diastolic blood pressure ranged from 14.3 to 25.4 mmHg
      across hydroxocobalamin doses compared with -3.0 to 3.8 mmHg in the corresponding
      placebo groups. Two allergic reactions that occurred within minutes after start
      of the 5- and 10-g hydroxocobalamin infusions were successfully managed with
      dexamethasone and/or dimethindene maleate. CONCLUSION: Timely intervention for
      acute cyanide poisoning could entail administration of an antidote in the
      prehospital setting based on a presumptive diagnosis. Results of this placebo
      controlled study in healthy volunteers corroborate previous studies and French
      postmarketing experience in cyanide-exposed patients in suggesting that the
      safety profile of hydroxocobalamin is consistent with prehospital or hospital
      use.

PMID- 16990191
TI  - Nitric oxide scavenging by hydroxocobalamin may account for its hemodynamic
      profile.
AB  - BACKGROUND: Antidotal doses of hydroxocobalamin are associated with transient
      increases in blood pressure in some animals and humans. These studies in
      anesthetized rabbits were undertaken to explore the possible mechanisms
      underlying the hemodynamic effects of hydroxocobalamin by investigating 1)
      possible hemodynamic effects of cyanocobalamin, which is formed on a molar-to
      molar basis when hydroxocobalamin binds cyanide, and 2) the interference of
      hydroxocobalamin with the endothelial nitric oxide system. METHODS: Study 1
      investigated the hemodynamic effects of cyanocobalamin. This study included two
      treatment arms: 1) cyanocobalamin (75 mg/kg, IV) followed by saline (n = 7) and
      2) saline followed by cyanocobalamin (n = 7). Study 2 assessed the hemodynamic
      effects of hydroxocobalamin (75 mg/kg, IV) in the presence and absence of the
      nitric oxide synthase inhibitor L-Nomega-nitro-L-arginine methyl ester (L-NAME;
      30 mg/kg, IV). Nitric oxide synthase inhibition itself increases blood pressure.
      Thus, as part of Study 2, the hemodynamic effects of hydroxocobalamin were also
      investigated in the presence of an equipressor dose of angiotensin II (ANGII;
      0.05 microg/kg/min, IV) in order to determine whether elevated blood pressure per
      se could interfere with hydroxocobalamin's hemodynamic effects. This study
      included six treatment arms (designated as first treatment + second treatment):
      saline + saline (n = 5), L-NAME + saline (n = 7), saline + hydroxocobalamin (n =
      7), L-NAME + hydroxocobalamin (n = 7), ANGII + hydroxocobalamin (n = 7), and
      ANGII + saline (n = 7). RESULTS: In Study 1, the effects of cyanocobalamin on
      hemodynamic parameters were indistinguishable from those of saline. In Study 2,
      hydroxocobalamin infusion was associated with moderate hemodynamic effects,
      including an increase in systemic vascular resistance, an increase in blood
      pressure, and a decrease in cardiac output. Administration of L-NAME abolished
      the effects of hydroxocobalamin on all hemodynamic parameters. ANGII at a dose
      producing a pressor response comparable to that of L-NAME did not influence the
      hydroxocobalamin-associated hemodynamic changes. CONCLUSION: These studies in
      anesthetized rabbits demonstrate that the moderate pressor effect of
      hydroxocobalamin is not related to the formation of cyanocobalamin but is very
      likely related to the scavenging of nitric oxide by hydroxocobalamin.

PMID- 16990192
TI  - Prehospital administration of hydroxocobalamin for smoke inhalation-associated
      cyanide poisoning: 8 years of experience in the Paris Fire Brigade.
AB  - INTRODUCTION: This article reports the results of a retrospective study of 8
      years of experience of the Paris Fire Brigade with the prehospital use of
      hydroxocobalamin. METHODS: The head physician at the Paris Fire Brigade extracted
      and summarized data from standardized forms completed at the fire scene and, when
      available, hospital reports to assess survival status and clinical parameters
      associated with the use of hydroxocobalamin for each patient who received it for
      smoke inhalation-associated cyanide poisoning from 1995 to 2003. RESULTS: Of the
      101 patients administered hydroxocobalamin, 30 survived, 42 died (17 at the fire
      scene and 25 at the intensive-care unit), and survival status was not known in
      the remaining 29 patients. Among the 72 patients for whom survival status was
      known, survival rate was 41.7% after the administration of hydroxocobalamin. Of
      the 38 patients found in cardiac arrest, 21 had a return of spontaneous
      circulation during prehospital care. Of the 12 patients who were initially
      hemodynamically unstable (systolic blood pressure 0 to < or =90 mmHg), 9
      recovered systolic blood pressure an average of 30.6 minutes after the start of
      hydroxocobalamin infusion. Among nonsedated patients in the sample as a whole (n
      = 52), mean (SD) Glasgow coma scale score improved from 7.9 (5.4) initially to
      8.5 (5.7) after administration of hydroxocobalamin. Among nonsedated patients who
      were initially neurologically impaired (n = 18), Glasgow coma scale score
      improved in 9 patients, did not change in 8 patients, and worsened in 1 patient.
      Two adverse events--red or pink coloration of urine or skin (n = 5) and cutaneous
      rash (n = 1)--were assessed as being possibly related to hydroxocobalamin.
      CONCLUSION: Hydroxocobalamin has a risk:benefit ratio rendering it suitable for
      prehospital use in the management of acute cyanide poisoning caused by smoke
      inhalation.

PMID- 16990194
TI  - Cyanide: understanding the risk, enhancing preparedness.

PMID- 16990195
TI  - Helicobacter pylori infection and antisecretory efficacy of proton-pump
      inhibitors in gastroesophageal reflux disease: a liaison dangereuse or an
      innocent interplay?

PMID- 16990196
TI  - Diagnostic pitfalls and accuracy of diagnosis in acute abdominal pain.
AB  - OBJECTIVE: To identify the differential diagnostic difficulties in acute
      abdominal pain at the emergency department and during hospitalization. MATERIAL
      AND METHODS: Patients with abdominal pain lasting for up to 7 days were
      registered during 1997-2000 and re-evaluated one year after discharge (n=2851).
      RESULTS: Diagnoses with low sensitivity at the emergency department but markedly
      increased sensitivity at discharge were non-specific abdominal pain with a
      sensitivity value at the emergency department of 0.43, appendicitis 0.80,
      gallstones 0.68, constipation 0.74 and peptic ulcer 0.26. Corresponding kappa
      values were 0.48, 0.74, 0.84, 0.88 and 0.93, respectively. Malignancy,
      gynaecological complaints, dyspepsia, urinary tract infection and diverticulitis
      displayed fairly good concordance between the preliminary and discharge
      judgements, but the predictive diagnostic value was still low at discharge.
      Sensitivity values at discharge were 0.40, 0.75, 0.73, 0.77 and 0.83,
      respectively. Among 479 surgically treated patients, 104 initially received a
      diagnosis usually not requiring surgery and had a median delay until operation of
      22 h (95% CI 30-50 h), compared with 8 h (12-18 h) for referrals. CONCLUSIONS:
      Non-specific abdominal pain is the main differential diagnostic problem in the
      emergency department also for diagnoses requiring surgery. Constipation is a
      diagnostic pitfall and when making this diagnosis a careful re-evaluation is
      necessary.

PMID- 16990197
TI  - Effect of rabeprazole and omeprazole on the onset of gastro-oesophageal reflux
      disease symptom relief during the first seven days of treatment.
AB  - OBJECTIVE: Gastro-oesophageal reflux disease (GORD) symptoms have a significant
      impact on patients' well-being. Onset of symptom relief is therefore an important
      consideration in GORD treatment. The primary objective was to compare the
      efficacy of rabeprazole (20 mg) and omeprazole (20 mg) regarding onset of
      heartburn control during the first 7 days of treatment in patients with erosive
      oesophagitis. Secondary objectives included maintenance of sustained heartburn
      control, control of other GORD symptoms (e.g. acid regurgitation, epigastric
      pain, dysphagia), effect on quality of life, patient satisfaction with treatment,
      and adverse events. MATERIAL AND METHODS: In this multicentre, randomized,
      parallel-group, double-blind, comparative study, performed in Europe and Iceland,
      patients with endoscopically confirmed erosive oesophagitis were randomized to
      receive once-daily treatment with rabeprazole 20 mg (n=358) or omeprazole 20 mg
      (n=359) for 7 days. Symptoms were recorded (scored on a 5-point Likert scale)
      twice daily by the patients on their diary cards. RESULTS: Median time to reach
      heartburn control was 1.5 days for both the rabeprazole and omeprazole groups
      (p<0.43). The results were similar between treatments for other study parameters.
      Both treatments were well tolerated. CONCLUSIONS: Unlike previous studies, no
      significant differences were found between treatments with rabeprazole (20 mg)
      and omeprazole (20 mg) in this study. Further studies are needed to evaluate the
      potential benefit of fast-acting proton-pump inhibitors, such as rabeprazole,
      with respect to onset of symptom control in erosive GORD.

PMID- 16990198
TI  - Effect of dietary sodium chloride on gastro-oesophageal reflux: a randomized
      controlled trial.
AB  - OBJECTIVE: It has been suggested that a high consumption of sodium chloride
      (NaCl) is associated with reflux symptoms. The objective of this study was to
      investigate the effect of increased dietary NaCl intake on gastro-oesophageal
      reflux and reflux mechanisms. MATERIAL AND METHODS: In this double-blind, placebo
      controlled, crossover study 10 healthy male subjects received 5 g NaCl or placebo
      in capsules per day for one week, after which concurrent manometric, pH and
      impedance monitoring was carried out for 4.5 h. RESULTS: Oesophageal acid
      exposure time (pH < 4) was similar for placebo (median 11% (25th 3-75th 36)) and
      NaCl (9% (1-36)). No differences in the numbers of reflux episodes were found for
      NaCl (16 (13.5-22)) and placebo (23 (14.8-27)). Furthermore, similar numbers of
      liquid acid reflux episodes (placebo 12 (6.5-17.3); NaCl 10 (2.3-14.3)), liquid
      weakly acidic reflux episodes (placebo 5.5 (4-12.3); NaCl 6.5 (3-10.8)) and
      gaseous reflux episodes (placebo 1 (0-1.8); NaCl 2 (0-3)) were seen. In both
      conditions transient lower oesophageal sphincter relaxations (TLOSRs) were the
      most common reflux mechanism, followed by swallow-induced reflux. High salt
      intake lowered LOS pressure overall and in the first postprandial hour (p<0.01).
      CONCLUSIONS: High dietary sodium intake does not increase gastro-oesophageal
      reflux in healthy volunteers, despite a decrease in LOS pressure.

PMID- 16990199
TI  - Does Helicobacter pylori infection influence response rate or speed of symptom
      control in patients with gastroesophageal reflux disease treated with
      rabeprazole?
AB  - OBJECTIVE: The findings of several studies suggest that proton-pump inhibitors
      (PPIs) suppress gastric acid more effectively in Helicobacter pylori-infected (Hp
      +) than in non-infected (Hp -) patients, but there has been no evaluation of the
      short-term clinical response. MATERIAL AND METHODS: Results of the first week of
      treatment with rabeprazole in Hp+ and Hp- patients with gastroesophageal reflux
      disease (GERD) were compared in a large prospective open-label, multicenter,
      cohort study in general and specialized practices. GERD patients were recruited
      on the basis of either typical symptoms alone or endoscopic results, assessed for
      H. pylori infection and treated with rabeprazole (20 mg). Heartburn and
      regurgitation symptoms were assessed daily during the first 7 days. Outcome
      parameters were calculated for both symptoms and compared between Hp+ and Hp-
      patients. RESULTS: Data on 1548 patients (74.5% Hp-, 25.5% Hp + ) were available.
      Mean heartburn and regurgitation scores decreased during the first week. For both
      symptoms, more than 70% of the patients had "adequate" symptom relief at day 5,
      and more than 80% at day 7. "Complete" symptom relief was reached in more than
      70% of patients. Mean onset of adequate symptom control was about 4 days. In Hp+
      and Hp- patients there was no difference in response for any of the parameters.
      CONCLUSIONS: Among patients treated with rabeprazole in clinical practice, H.
      pylori infection or its absence has no effect on the speed or degree of GERD
      symptom relief. Infected patients and non-infected patients can therefore be
      treated with a similar dose. When treating heartburn with rabeprazole, physicians
      do not need to consider the patient's H. pylori status and most patients (>80%)
      have adequate symptom relief after just a few days of treatment.

PMID- 16990200
TI  - Effects of posture on the physiology of gastric emptying: a magnetic resonance
      imaging study.
AB  - OBJECTIVE: Gastric contents empty from the stomach despite frequent changes in
      body position. The mechanism that maintains gastric emptying independent of
      position is poorly understood. The aim of this study was to determine the effects
      of body position on gastric emptying and motor function. MATERIAL AND METHODS:
      Twelve volunteers were investigated in seated position (SP) and upside-down
      position (UDP) after ingestion of 300 ml water. Magnetic resonance imaging
      provided a non-invasive assessment of gastric emptying and volumes, intragastric
      distribution and peristaltic function. RESULTS: A marked difference in
      distal/proximal intragastric distribution between UDP and SP was present (7%
      versus 40%; p < 0.01). Gastric-emptying time was similar but emptying pattern was
      linear in UDP and exponential in SP. Peristalsis was slower in UDP than SP (2.75
      versus 2.96 min-1; p < 0.01), but no correlation was found between peristaltic
      frequency and the rate of gastric emptying in either position. Postprandial
      volume response (gastric relaxation) was greater in UDP than SP (280 versus 250
      ml; p < 0.05). A correlation was found between gastric relaxation and gastric
      emptying time in SP (r2=0.46) but not in UDP. CONCLUSIONS: The stomach maintains
      the rate of gastric emptying despite radical changes in body position and
      intragastric distribution of gastric contents. In SP, hydrostatic pressure
      (modulated by gastric tone) dictates the gastric emptying. In UDP, gastric
      emptying also appears to be mediated by continuous adaptation of gastric tone.
      These findings provide support for the hypothesis that the mechanism of gastric
      emptying resembles a "pressure pump" rather than a "peristaltic pump".

PMID- 16990202
TI  - Absence of association between the multidrug resistance (MDR1) gene and
      inflammatory bowel disease.
AB  - OBJECTIVE: The multidrug resistance (MDR1) gene encodes for P-glycoprotein, a
      drug efflux pump. Mice deficient for the MDR1a gene spontaneously develop
      colitis. In humans, a polymorphism in exon 26 (C3435T) is associated with reduced
      expression levels and function of MDR1. Currently there are controversial data on
      the association between MDR1 and inflammatory bowel disease (IBD). The purpose of
      this study was to examine the involvement of this gene in IBD in a large
      population of Dutch patients with IBD and family-based controls. MATERIAL AND
      METHODS: A total of 781 IBD cases and 315 controls were investigated. CD
      phenotypes were determined according to the Vienna Classification. Individuals
      were genotyped for six single nucleotide polymorphisms (SNPs) close to and in the
      MDR1 locus. This included the C3435T variant and six microsatellite markers close
      to and in the MDR1 locus. Single locus association analysis, haplotype
      association analysis and haplotype sharing statistic (HSS) were used to search
      for differences between patients and controls. RESULTS: No association was
      observed for any of the SNPs with IBD as a group, or for ulcerative colitis,
      Crohn's disease and Crohn's disease phenotypes, either by single locus or
      haplotype association analysis or by HSS. CONCLUSIONS: No association was
      observed between the MDR1 gene and IBD. This suggests that it is unlikely that
      MDR1 plays a role in IBD susceptibility.

PMID- 16990201
TI  - Ingestion of difructose anhydride III, a non-digestible disaccharide, improves
      postgastrectomy osteopenia in rats.
AB  - OBJECTIVE: Total gastrectomy produces osteopenia with calcium malabsorption. We
      previously demonstrated that difructose anhydride III (DFAIII), a non-digestible
      disaccharide, stimulates intestinal calcium absorption in normal and
      ovariectomized rats. In the present study, we examined the effects of feeding
      DFAIII on gastrectomy-induced calcium malabsorption and osteopenia in rats. The
      potential of DFAIII to promote large intestinal calcium absorption was also
      evaluated through comparison with that of fructooligosaccharides (FOS). MATERIAL
      AND METHODS: Male Sprague-Dawley rats were divided into two groups: totally
      gastrectomized and sham-operated rats. After a postoperative recovery period,
      rats from each group were divided into three subgroups and fed the control,
      DFAIII (30 g/kg), or FOS (30 g/kg) diet for 28 days. RESULTS: Total gastrectomy
      severely reduced net calcium absorption, femoral calcium content and bone mineral
      density, resulting in fragility of the femur. DFAIII or FOS feeding partly and
      similarly restored the lowered calcium absorption and femoral variables, with an
      increase in the total short-chain fatty acid pool in the cecum. In gastrectomized
      rats, net calcium absorption was correlated with several cecal parameters,
      suggesting that cecal fermentation of DFAIII is associated with the improvement
      in gastrectomy-induced calcium malabsorption. Urinary excretion of
      deoxypyridinoline (D-Pyr) as a marker of bone resorption was increased by
      gastrectomy, and the elevated D-Pyr excretion was suppressed by feeding DFAIII.
      CONCLUSIONS: Supplemental feeding of DFAIII partly prevents postgastrectomy
      osteopenia as a result of an improvement in calcium absorption. Our results
      suggest that the promotive effects of DFAIII on calcium absorption in the large
      intestine are comparable to those of FOS.

PMID- 16990203
TI  - A traditional Japanese medicine mitigates TNBS-induced colitis in rats.
AB  - OBJECTIVE: Differences in dietary habits may be one of the reasons that the
      incidence of inflammatory bowel disease has remained lower in Japan than in
      Western countries. We investigated whether a traditional Japanese medicine
      (Strong Wakamto), based on Aspergillus oryzae koji, would exert any effect on
      experimental colitis in rats. MATERIAL AND METHODS: Colitis was induced using an
      enema of trinitrobenzene sulfonic acid (TNBS) and ethanol. Strong Wakamto was
      administered for 28 days before induction of colitis and for 7 days thereafter,
      and the effect of this medicine was evaluated. RESULTS: Treatment with 5% Strong
      Wakamto improved loss of body-weight, increased colon weight and significantly
      decreased the histological damage score for colon mucosa. Decreases in faecal
      Lactobacillus sp., superoxide dismutase activity and zinc concentrations, and the
      increased IL-1beta expression in colonic tissue after TNBS enema were improved
      when Strong Wakamto was given. The present in vitro studies indicate that
      administration of Strong Wakamto prevents lipopolysaccharide-induced TNF-alpha
      production in human macrophages. CONCLUSIONS: Oral administration of Strong
      Wakamto mitigates experimental inflammatory bowel disease induced by TNBS enema
      in rats. The beneficial effects seem attributable to a combination of balancing
      microflora, immunomodulatory effects on gut macrophages, and enhancement of anti
      superoxide activity in colonic tissues.

PMID- 16990204
TI  - Azathioprine as a postoperative prophylaxis reduces symptoms in aggressive
      Crohn's disease.
AB  - OBJECTIVE: Recurrence of Crohn's disease (CD) after surgery is common.
      Azathioprine/6-mercaptopurine (Aza/6-MP) is effective in controlling medically
      induced remission but, so far, has only been sparsely investigated after
      surgically induced remission. This study comprises a subset of CD patients
      considered to have an aggressive disease course and chosen for treatment with Aza
      postoperatively. MATERIAL AND METHODS: In 1989-2000, a total of 100 patients with
      CD were given Aza/6-MP as a postoperative prophylaxis. Fourteen Aza/6-MP
      intolerant patients were compared with 28 Aza-tolerant patients, matched for
      gender, age, and duration of disease. Patients were prospectively registered for
      symptoms using a modified Crohn's disease activity index (CDAI) and perceived
      health was assessed on a visual analogue scale (VAS). The primary outcome
      variable was the modified CDAI postoperatively integrated over time; other
      variables were time to first relapse (modified CDAI >or= 150), time to first
      repeated surgery, number of courses of steroids, and repeated surgery per year of
      follow-up. Patients were followed for a median of 84.7 months (23.2-140).
      RESULTS: The modified CDAI integrated over time was 93 for Aza-treated patients
      compared with 184 for controls (p=0.01) and time to first relapse was 53 and 24
      months, respectively (p<0.05). Aza-treated patients needed fewer courses of
      corticosteroids (p=0.05) compared with controls. Perceived health did not differ
      between the groups, nor did need of repeated surgery. Time to first repeat
      operation was 53 and 37 months, respectively. CONCLUSIONS: In CD patients
      considered to have an aggressive disease course, Aza reduced symptoms after
      surgery and prolonged the time to symptomatic relapse. The findings support a
      role for Aza as a postoperative maintenance treatment in CD.

PMID- 16990205
TI  - The Short Health Scale: a valid measure of subjective health in ulcerative
      colitis.
AB  - OBJECTIVE: Assessment of health-related quality of life (HRQOL) is important in
      both clinical practice and clinical trials, and several multi-item questionnaires
      are currently in use. We have devised and evaluated a simplified four-item
      questionnaire, the Short Health Scale (SHS), representing each of four health
      dimensions: (a) symptom burden, (b) social function, (c) disease-related worry
      and (d) general well-being. MATERIAL AND METHODS: Three hundred patients with
      ulcerative colitis completed the SHS and three other HRQOL questionnaires (IBDQ,
      RFIPC and PGWB). Half of the patients repeated the questionnaires after 6 months 
      or earlier if disease activity changed. Test-retest reliability was derived from
      measurements of the SHS questions, 2 weeks apart, on 18 patients in remission.
      RESULTS: Patients in relapse scored higher on each of the four SHS questions than
      patients in remission (p < 0.001). Each of the four SHS scores were associated
      with results of their corresponding health dimension obtained with the other
      three questionnaires (rs=0.57-0.78, p < 0.001) (validity). The results of the SHS
      proved stable on repeated measurement with a 2-week interval in patients in
      remission (rs=0.71-0.91, p < 0.01) (test-retest reliability). Patients with a
      change in disease activity had a significant change in their SHS scores (p <
      0.05) (responsiveness). CONCLUSIONS: The SHS is a valid, reliable and responsive
      measure of subjective health in patients with ulcerative colitis. It is simple to
      administer, quickly completed and the results do not need further calculations.
      The SHS can be used in clinical trials and in clinical practice to identify the
      patient's main problems affecting health.

PMID- 16990206
TI  - Long-term outcome after intestinal resection for Crohn's disease.
AB  - OBJECTIVE: To assess the need for intestinal repeat resection for recurrence of
      Crohn's disease in patients observed for more than 20 years after the first
      resection. MATERIAL AND METHODS: Data were gathered retrospectively from the
      medical records of 53 (28 F) consecutive patients with Crohn's disease from May
      1954 to December 2002. Median age at first intestinal resection was 24.5 (range
      13-65) years, and median observation time thereafter was 26.5 (20.1-48.6) years.
      Disease location and behaviour were defined according to the Vienna
      classification. RESULTS: The 53 patients had an average 2.7 and a median 2
      intestinal resections. Out of 144 intestinal resections (77.1%) 111 were
      performed during the first three operations; no alterations in distribution of
      ileal, ileocolic and colic resections were found. From the first to the third
      operation there was an increase in penetrating disease from 15% to 39% (p=0.046)
      concomitant with a decrease in stricturing disease from 72% to 44% (p=0.048) of
      the patients. There was also a corresponding decrease in ileocolic disease from
      45% to 5% (p=0.003) and a tendency towards an increase in ileal disease from 38%
      to 67%. One patient died (1.8%) from rectosigmoid perforation after the third
      resectional operation. Six patients needed reoperation (11.3%) for ileus,
      anastomotic bleeding, rectosigmoidal perforation and abdominal pain. Thirty-four
      patients (64.2%) needed intestinal repeat resection (median 8.3 years) during
      25.3 years after the first repeat resection. CONCLUSIONS: This study indicates a
      diminution of Crohn's disease activity with time, as demonstrated by no need for
      intestinal repeat resection more than 25 years after the first resection.

PMID- 16990207
TI  - Influence of smoking habits and CARD15 mutations on the onset of Crohn's disease.

PMID- 16990208
TI  - Treatment of severe refractory pruritus with fractionated plasma separation and
      adsorption (Prometheus).
AB  - OBJECTIVE: Severe pruritus is a serious complication of cholestatic liver
      disease. Prometheus is a recently introduced extracorporeal liver support system
      with direct toxin adsorption of the patient's albumin fraction (FPSA;
      fractionated plasma separation and adsorption). Here we report on the effect of
      Prometheus therapy in patients with intractable cholestatic pruritus. MATERIAL
      AND METHODS: Seven patients with different liver diseases and severe pruritus
      refractory to all medical treatment efforts for more than 4 weeks were treated
      with Prometheus (3-5 times, 18+/-3 h total). Pruritus intensity was assessed
      using the visual analogue scale (VAS; from 0 = no pruritus to 10 = unbearable
      pruritus), and VAS, serum bile acids and total bilirubin were evaluated directly
      before and after Prometheus treatment, as well as 4 weeks later. RESULTS: After
      Prometheus therapy, VAS values had dropped significantly from 9+/-1 to 3+/-3
      (p<0.001). Likewise, serum bile acids decreased (from 248+/-192 to 101+/-85
      micromol/l; p<0.03). All patients, with the exception of one with no initial bile
      acid elevation, reported a pronounced improvement in pruritus with Prometheus
      therapy, although in two anicteric patients the amelioration lasted only a few
      days. In the other four patients a distinct benefit was still observed 4 weeks
      after the treatment. CONCLUSIONS: Prometheus therapy significantly improved
      refractory pruritus in all patients with elevated bile acid levels, but in some
      patients the clinical benefit was of short duration. The clinical findings
      suggest that we have to better characterize those patients who might derive a
      long-lasting benefit from this invasive and expensive treatment.

PMID- 16990209
TI  - Interstitial cells of Cajal in the murine gallbladder.
AB  - OBJECTIVE: The presence of interstitial cells of Cajal (ICC) has been described
      throughout the digestive tract. In this study, we investigated whether ICC also
      exist in the gallbladder wall of CD1 mice. MATERIAL AND METHODS:
      Immunofluorescent confocal microscopy was used to identify the morphology and
      distribution of ICC in either whole-mount flat preparations or enzyme-dispersed
      cells from the gallbladder of CD1 mice. Methylene blue staining and transmission
      electron microscopy were performed to detect the presence of ICC, and reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot were used to
      confirm the expressions of ICC-specific marker c-kit in the gallbladder tissues.
      RESULTS: The presence of c-kit-positive cells was demonstrated in both the
      gallbladder wall and the enzyme-dispersed cells. The ICC were distributed
      throughout the wall of the gallbladder and organized into a network. Under
      transmission electron microscopy, ICC were characterized by their well-developed
      perinuclear endoplasmic reticulum, abundant mitochondria, free ribosomes and
      intermediate filaments, and distinctive caveolae and lack of myosin filaments.
      The expressions of ICC-specific marker c-kit were also confirmed in the
      gallbladder tissue. CONCLUSION: The murine gallbladder wall contains ICC.

PMID- 16990210
TI  - Characterization and clinical course of hepatobiliary carcinoma in patients with
      primary sclerosing cholangitis.
AB  - OBJECTIVE: Primary sclerosing cholangitis (PSC) confers a high risk of
      development of hepatobiliary carcinoma (HBC). The aim of the study was to
      identify indicators and risk factors for developing HBC in PSC patients. MATERIAL
      AND METHODS: Thirty-nine PSC patients with HBC at time of HBC diagnosis were
      compared with 101 PSC patients without HBC at time of acceptance for liver
      transplantation. RESULTS: Eighteen of these patients (46.2%) developed HBC within
      one year after diagnosis of PSC. In PSC patients with HBC male gender, nicotine
      abuse, long duration of inflammatory bowl disease (IBD), clinical symptoms,
      elevation of CA 19-9, as well as dominant bile duct stenosis were significantly
      more frequent (p<0.05) compared with the PSC control group. A cross-validated
      sensitivity and specificity of 85% and 97%, respectively, for the detection of
      HBC was obtained using the following parameters: weight loss, elevation of CA 19
      9 >or= 200 kU/l, and dominant bile duct stenosis. CONCLUSIONS: HBC is not
      necessarily a late complication of end-stage PSC. A long history of IBD, male
      gender, and nicotine abuse are risk factors for the development of HBC. In
      particular, CA 19-9, body-weight and dominant bile duct stenosis are valuable
      indicators in detecting HBC in PSC patients.

PMID- 16990211
TI  - Liver steatosis in hepatitis C positive hemodialysis patients and factors
      affecting IFN-2a treatment.
AB  - OBJECTIVE: Hepatitis C virus (HCV) infection is endemic among hemodialysis (HD)
      patients. It is well known that HCV causes approximately 50% of hepatosteatosis
      in patients with normal renal function and that this rate is higher in patients
      infected with genotype 3. The aim of this study was to investigate the rate of
      steatosis, the regression in steatosis with interferon (IFN) treatment and
      factors affecting IFN treatment in hemodialysis patients with chronic hepatitis C
      (CHC). MATERIAL AND METHODS: Thirty-seven HD patients with CHC were included in
      the study. All patients received hemodialysis treatment three times a week during
      the follow-up period. Patients were treated with 3 million units (MU) of IFN
      alpha 2a monotherapy for at least 6 months. All patients were evaluated by liver
      biopsy before therapy and 16 were evaluated at 12-month follow-up. RESULTS: Mean
      age of the 37 patients (23 M, 14 F) was 44+/-11.6 years and body mass index was
      21.8+/-1.8 kg/m2. Twenty-eight of the patients included in the study (75.7%) were
      of genotype 1b. RNA response after treatment was 78.4% and sustained response
      after the follow-up period of 14.9+/-8 months was 54%. Total cholesterol values
      were directly proportional to RNA response (p<0.003) and inversely correlated
      with resistance to treatment (p<0.008). Triglyceride values were inversely
      correlated with resistance to treatment (p<0.041). At evaluation of steatosis
      scores in baseline liver biopsy, severe and mild to moderate steatosis was found
      in 3 (8.1%) and 16 (43.2%) patients, respectively. In 18 patients (48.7%) there
      was no steatosis. The rate of steatosis was found to be 44% in control biopsies.
      While there was no regression in the rates of steatosis (p=0.499), it was found
      that steatosis regressed after IFN treatment in two patients infected with
      genotype 3. No correlations were observed between HCV genotype, sustained
      response and liver steatosis. CONCLUSIONS: Response and sustained response rates
      of HD patients with HCV in a Turkish population were found to be high after IFN
      monotherapy. With the exception of two patients infected with genotype 3a, the
      rate of liver steatosis was found to be high and did not change after IFN
      treatment in HD patients with CHC.

PMID- 16990212
TI  - Conservative management of a three-day-old esophageal perforation with feeding
      jejunostomy and prokinetic drug.
AB  - Spontaneous esophageal perforation is a well-recognized, life-threatening
      emergency. The spectrum of presentation is a major reason for errors in diagnosis
      and the failure to institute prompt and imminent management. A case of
      Boerhaave's syndrome, diagnosed and managed non-operatively in a tertiary center
      three days after tear, is described. The diagnosis was confirmed with a series of
      gastrograffin esophagograms which revealed a leak in the lower part of the
      esophagus, with hydropneumothorax.

PMID- 16990213
TI  - TRP channels: molecular diversity and physiological function.
AB  - Calcium ions (Ca(2+)) are particularly important in cellular homeostasis and
      activity. To elicit physiologically relevant timing and spatial patterns of
      Ca(2+) signaling, ion channels in the surface of each cell precisely control
      Ca(2+) influx across the plasma membrane. A group of surface membrane ion
      channels called receptor-activated cation/Ca(2+) channels (RACCs) are activated
      by diverse cellular stimuli from the surrounding extracellular environment via
      receptors and other pathways such as heat, osmotic pressure, and mechanical and
      oxidative stress. An important clue to understanding the molecular mechanisms
      underlying the functional diversity of RACCs was first attained by molecular
      identification of the transient receptor potential (trp) protein (TRP), which
      mediates light-induced depolarization in Drosophila photoreceptor cells, and its
      homologues from various biological species. Recent studies have revealed that
      respective TRP channels are indeed activated by characteristic cellular stimuli.
      Furthermore, the involvement of TRP channels has been demonstrated in the
      signaling pathways essential for tissue-specific functions as well as ubiquitous
      biological responses, such as cell proliferation, differentiation, and death.
      These findings encourage the usage of TRP channels and their signalplexes as
      powerful tools for developing novel pharmaceutical targets.

PMID- 16990214
TI  - Microvascular display of xanthine oxidase and NADPH oxidase in the spontaneously
      hypertensive rat.
AB  - OBJECTIVE: Oxygen free radical production in hypertension may be associated with
      elevated arteriolar tone and organ injury. Previous results suggest an enhanced
      level of oxygen free radical formation in microvascular endothelium and in
      circulating neutrophils associated with xanthine oxidase activity in the
      spontaneously hypertensive rats (SHR) compared with their normotensive controls,
      the Wistar Kyoto rats (WKY). The aim of this study was to gain more detailed
      understanding of where oxidative enzymes are located in the microcirculation.
      METHODS: An approach was developed to delineate the cellular distribution of two
      selected oxidative enzymes, xanthine oxidase and nicotinamide adenine
      dinucleotide phosphate (NADPH) dependent oxidase (protein 67-kDa fraction).
      Immunolabeling with peroxidase substrate was utilized, which permits full
      delineation of the primary antibody in all microvascular structures of the
      mesentery. RESULTS: Xanthine oxidase is present in the endothelium of all
      segments of the microcirculation, in mast cells, and in parenchymal cells of the
      mesentery. NADPH oxidase can be detected in the endothelium, leukocytes, and mast
      cells and with lower levels in parenchymal cells. The mesentery of WKY and SHR
      has similar enzyme distributions with enhancements on the arteriolar and venular
      side of the microcirculation that coincide with the sites of enhanced free
      radical production recently reported. Immune label measurements under
      standardized conditions indicate that both enzymes are significantly enhanced in
      the SHR. Adrenalectomy, which serves to reduce the blood pressure and free
      radical production of the SHR to normotensive levels, leads to a reduction of
      NADPH and xanthine oxidase to normotensive levels, while supplementation of
      adrenalectomized SHR with dexamethasone significantly increases the oxidase
      expression in several parts of the microcirculation to levels above the WKY rats.
      CONCLUSION: The results indicate that enhanced expression of NADPH and xanthine
      oxidase in the SHR depends on an adrenal pathway that is detectable in the
      arteriolar and venular network at high and low pressure regions of the
      circulation.

PMID- 16990215
TI  - Inhibition of NAD(P)H oxidase alleviates impaired NOS-dependent responses of pial
      arterioles in type 1 diabetes mellitus.
AB  - OBJECTIVE: The goal was to identify the role of NAD(P)H oxidase in
      cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). METHODS: In a
      first series of studies, rats were assigned to nondiabetic, diabetic
      (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/day in drinking
      water)-treated and diabetic-apocynin-treated groups. Two to three months later,
      the authors examined in vivo responses of pial arterioles to nitric oxide
      synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and 
      independent (nitroglycerin) agonists. Next, they used Western blot analysis to
      examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels
      and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they
      measured superoxide production by parietal cortex tissue in nondiabetic and
      diabetic rats. RESULTS: Acetylcholine- and ADP-induced dilatation of pial
      arterioles was impaired in diabetic compared to nondiabetic rats. In addition,
      while apocynin did not alter responses in nondiabetic rats, apocynin alleviated
      T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and
      gp91phox proteins were elevated in cerebral microvessels and parietal cortex
      tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal
      production of superoxide was increased in diabetic compared to nondiabetic rats
      and apocynin decreased this basal production. CONCLUSIONS: The findings suggest
      that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism
      related to the formation of superoxide via activation of NAD(P)H oxidase.

PMID- 16990217
TI  - Sensitization of coronary alpha-adrenoceptor vasoconstriction in the prediabetic
      metabolic syndrome.
AB  - OBJECTIVE: This study tested whether alpha -adrenoceptor-mediated coronary
      vasoconstriction is augmented in the metabolic syndrome and is accompanied by the
      alteration of specific alpha(1)- and alpha(2)-coronary adrenoceptors. METHODS:
      Studies were conducted in control and chronically high-fat-fed (6 weeks of 60%
      calories from fat) dogs with metabolic syndrome. Alterations in coronary
      alpha(1B)-, alpha(1D)-, and alpha(2A)-adrenoceptor mRNA and protein expression
      were examined by real-time PCR and Western analyses, respectively. Coronary blood
      flow and its response to intracoronary infusion of either the alpha1-adrenoceptor
      agonist methoxamine (0.1-3 mg) or the alpha(2)-adrenoceptor agonist BHT-933 (0.1
      3 mg) were measured in anesthetized dogs. RESULTS: Basal plasma epinephrine and
      norepinephrine levels were higher in the high-fat-fed dogs compared to controls.
      Real-time PCR revealed no alterations of coronary artery or arteriole alpha1B-,
      alpha(1D)-, and alpha(2A)-adrenoceptor mRNA expression. However, Western blot
      analysis showed a significant decrease in alpha(2A)-adrenoceptor protein density
      with no change in alpha(1B)- or alpha(1D)-adrenoceptors. Methoxamine and BHT-933
      produced dose-dependent decreases in coronary blood flow, but the decrease in
      coronary flow to methoxamine was significantly greater (approximately 20%) in
      dogs with the metabolic syndrome. No differences in the coronary flow response to
      BHT-933 were noted. CONCLUSIONS: These results indicate that the metabolic
      syndrome is associated with sensitization of alpha1- and alpha2-adrenoceptor
      signaling that could significantly limit control of coronary blood flow when the
      sympathetic nervous system is activated.

PMID- 16990218
TI  - Lymph flow, shear stress, and lymphocyte velocity in rat mesenteric prenodal
      lymphatics.
AB  - OBJECTIVE: To measure lymphocyte velocity, lymphatic contraction, and shear
      stress in phasically contracting lymphatics in situ. METHODS: A high-speed video
      system was used to capture multiple contraction cycles in rat mesenteric
      lymphatic preparations. The images were analyzed to determine fluid velocity,
      volume flow rate, wall shear stress, and retrograde flow. RESULTS: Lymphocyte
      density and flux varied from 326 to 35,500 cells/microL and 206 to 2,030
      cells/min, respectively. Lymphatics contracted phasically, with a mean diameter
      91 +/- 9.0 microm and amplitudes of 39%. Lymph velocity varied with the phasic
      contractions in both direction and magnitude with an average of 0.87 +/- 0.18 and
      peaks of 2.2-9.0 mm/s. The velocity was approximately 180 degrees out of phase
      with the contraction cycle. The average lymph flow was 13.95 +/- 5.27 microL/h
      with transient periods of flow reversal. This resulted in an average shear of
      0.64 +/- 0.14 with peaks of 4-12 dynes/cm(2). CONCLUSIONS: High-speed lymphocyte
      tracking provided the spatial and temporal resolution to measure lymphocyte flux
      throughout the phasic contraction. Poiseuille flow was a reasonable model for
      estimating wall shear stress through most of the phasic contraction cycle of the
      intervalvular lymphatic segments. Shear rate was low but had large variations in
      magnitude compared to that seen in blood vessels.

PMID- 16990216
TI  - Acupuncture reduces experimental renovascular hypertension through mechanisms
      involving nitric oxide synthases.
AB  - OBJECTIVE: To test the hypothesis that acupuncture on stomach 36 point (ST-36)
      reduces hypertension by activating nitric oxide synthase signaling mechanisms.
      METHODS: The authors used the two-kidney, one-clip renal hypertension (2K1C)
      hamster model with electroacupuncture treatment. RESULTS: Thirty-minute daily
      electroacupuncture treatment for 5 days reduced mean arterial pressure from 160.0
      +/- 7.6 to 128.0 +/- 4.3 mmHg (mean +/- SEM), compared to 115.0 +/- 7.2 mmHg in
      sham-operated hamsters. Electroacupuncture increased periarteriolar NO
      concentration from 309.0 +/- 21.7 nM to 417.9 +/- 20.9 nM in the 2K1C hamster
      cheek pouch microcirculation when measured with NO-sensitive microelectrodes.
      Hypertension reduced endothelial nitric oxide synthase (eNOS) and neuronal nitric
      oxide synthase (nNOS) proteins relative to the sham-operated control, as measured
      by Western blotting. Electroacupuncture prevented the reduction of eNOS and nNOS
      associated with hypertension and showed even higher eNOS and nNOS expressions
      than sham-operated control in stomach and cheek pouch tissues, which are on the
      stomach meridian. Analysis of liver tissue, a non-stomach-meridian organ,
      indicated that electroacupuncture did not have a significant benefit in terms of
      enhanced expressions of eNOS and nNOS in the treated 2K1C hypertensive group.
      CONCLUSIONS: Activation of eNOS and nNOS is one of the mechanisms through which
      ST-36 electroacupuncture reduces blood pressure; this reduction works through the
      stomach meridian.

PMID- 16990222
TI  - The effect of prosthesis alignment on the symmetry of gait in subjects with
      unilateral transtibial amputation.
AB  - A high degree of gait symmetry is characteristic of healthy gait. The aim of this
      study is to examine the symmetry of various gait parameters in subjects with
      unilateral trans-tibial amputation over a range of acceptable anteroposterior
      translational and tilt alignments, and further to examine if a consistent
      alignment of highest symmetry can be found. Acceptable alignments were determined
      by bench, static and dynamic testing on level and non-level surfaces. A total of
      15 kinetic and kinematic parameters were then measured in the seven subjects
      participating in this study. Results indicate that some parameters show
      consistently higher symmetries, particularly the vertical ground reaction force
      parameters and the stance duration, step length and time to full knee flexion
      during the swing phase. Symmetries in other parameters such as knee flexion at
      loading response, acceleration impulse, and peak anteroposterior propulsive force
      seem to have little relevance in determining whether the gait pattern for that
      prosthetic alignment is acceptable or not. While analysis of the symmetry of more
      relevant gait parameters may assist the prosthetist in consistently and
      objectively identifying a most symmetrical alignment within the acceptable range,
      further clinical study is required before any conclusions can be drawn regarding
      evaluation of symmetry as a tool in defining any optimum alignment.

PMID- 16990219
TI  - Mechanistically identified suitable biomarkers of exposure, effect, and
      susceptibility for silicosis and coal-worker's pneumoconiosis: a comprehensive
      review.
AB  - Clinical detection of silicosis is currently dependent on radiological and lung
      function abnormalities, both late manifestations of disease. Markers of
      prediction and early detection of pneumoconiosis are imperative for the
      implementation of timely intervention strategies. Understanding the underlying
      mechanisms of the etiology of coal workers pneumoconiosis (CWP) and silicosis was
      essential in proposing numerous biomarkers that have been evaluated to assess
      effects following exposure to crystalline silica and/or coal mine dust. Human
      validation studies have substantiated some of these proposed biomarkers and
      argued in favor of their use as biomarkers for crystalline silica- and CWP
      induced pneumoconiosis. A number of "ideal" biological markers of effect were
      identified, namely, Clara cell protein-16 (CC16) (serum), tumor necrosis factor
      alpha (TNF-alpha) (monocyte release), interleukin-8 (IL-8) (monocyte release),
      reactive oxygen species (ROS) measurement by chemiluminescence (neutrophil
      release), 8-isoprostanes (serum), total antioxidant levels measured by total
      equivalent antioxidant capacity (TEAC), glutathione, glutathione peroxidase
      activity, glutathione S-transferase activity, and platelet-derived growth factor
      (PDGF) (serum). TNF-alpha polymorphism (blood cellular DNA) was identified as a
      biomarker of susceptibility. Further studies are planned to test the validity and
      feasibility of these biomarkers to detect either high exposure to crystalline
      silica and early silicosis or susceptibility to silicosis in gold miners in South
      Africa.

PMID- 16990223
TI  - Clinical application of carbon fibre reinforced plastic leg orthosis for polio
      survivors and its advantages and disadvantages.
AB  - A prospective study was carried out on the clinical application and features of a
      carbon fibre reinforced plastic leg orthosis (carbon orthosis) for polio
      survivors. The subjects comprised 9 polio survivors, and 11 carbon knee-ankle
      foot orthoses (KAFOs) were prescribed, fabricated, and checked out at the
      authors' post-polio clinic. Walking was classified based on the functional
      ambulatory category, and the features of walking with a carbon orthosis were self
      evaluated by using a visual analogue scale. The period from modelling a cast to
      completion was 55 +/- 25 days; the weight of a carbon KAFO was 27.8% lighter than
      that of the ordinary KAFO; the standard carbon KAFO was 50% more expensive than
      the ordinary KAFO. The carbon KAFO remained undamaged for at least 2 years. It
      improved the scores in the functional ambulation categories, but there was no
      difference between walking with an ordinary and with a carbon KAFO. The self
      evaluation of walking with a carbon KAFO revealed that the subjects using a
      carbon KAFO were satisfied with their carbon KAFO. The carbon KAFO is
      lightweight, durable, slim and smart, and is positively indicated for polio
      survivors.

PMID- 16990224
TI  - Curve correction effect of rigid spinal orthosis in different recumbent positions
      in adolescent idiopathic scoliosis (AIS): a pilot MRI study.
AB  - In this pilot cross-sectional study, the effectiveness of rigid spinal orthoses
      in the correction of spinal curvature of 14 patients with moderate adolescent
      idiopathic scoliosis (AIS) at different recumbent positions (supine, prone, right
      and left decubitus) was investigated. Using magnetic resonance (MR) imaging and
      multi-planar reconstruction technique, evaluation of the scoliotic spine in the
      coronal, sagittal and axial planes and the effect of spinal orthosis on AIS at
      different recumbent positions was studied. There was significant reduction of
      coronal Cobb's angle (p < 0.05) with bracing at all four recumbent positions and
      the maximal reduction was found in the prone position (18% reduction). The
      sagittal Cobb's angle was only significantly reduced at the supine position while
      the axial rotation did not change significantly in all positions.

PMID- 16990225
TI  - The use of stock orthoses to assist gait in neuromuscular disorders: a pilot
      study.
AB  - This pilot study compares the effect on walking speed, in eight subjects with
      neuromuscular conditions, of wearing Ligaflex ankle-foot orthoses (AFO),
      Leafspring orthoses and shoes or with shoes alone. Range of motion, muscle
      strength and sensation were tested in the lower leg. Subjects underwent a
      standardized timed 10-m walking test five times in each of the orthoses and shoes
      as a measure of gait efficiency. A self-administered questionnaire was used to
      seek the subjects' perceptions of their functional difficulties and their
      opinions about the relative comfort and stability of these orthoses. Subjects had
      reduced ranges and strength of dorsiflexion and eversion. Some had proprioceptive
      deficiencies. Mean walking speed was 0.99 m/s (Leafspring) and 1.1 m/s (Ligaflex
      or shoes) compared to about 1.3 m/s for a normal population. Repeated measures
      ANOVA revealed that subjects were significantly slower in Leafspring compared to
      Ligaflex or to shoes. Questionnaire results rated the Leafspring as least
      comfortable and the Ligaflex most stable. Providing stability may be more
      important than assisting foot clearance when weakness is restricted to distal
      muscles. Further research is required to evaluate the comfort and effectiveness
      of orthoses to compensate for ankle instability in people with neuromuscular
      conditions.

PMID- 16990226
TI  - Clinical features and outcomes following bilateral lower limb amputation in
      Korea.
AB  - The objectives of this study were to evaluate the clinical features and outcomes
      of 43 bilateral lower limb amputees. The clinical features obtained included the
      causes of amputation, level of amputation, concurrent medical problems, and stump
      condition. Outcome measures were obtained using the activities of daily living
      (ADL) index, the Frenchay Activities Index (FAI), and mobility grading with
      prostheses or wheelchair. Of 33 amputees who were prosthetic ambulators, 22
      (67%), mainly bilateral trans-tibial (TT) amputees, were community ambulators,
      and participated in activities which included stair-walking, and six of 11
      household ambulators were combination trans-femoral (TF) and TT amputees. Of 10
      amputees who were wheelchair ambulators, only one was able to perform wheelchair
      transfers independently and five were independent wheelchair ambulators. Using
      the ADL index and FAI, there was no significant difference in scores according to
      the level of amputation (p > 0.05), but the scores of community prosthetic
      ambulators were significantly higher than those of wheelchair ambulators (p <
      0.05). Age was found to be negatively correlated with ADL index and FAI scores (r
      = -0.518 vs. r = -0.550) (p < 0.01). This study concludes that overall
      independence in ADL after bilateral lower limb amputation improved with young age
      and prosthetic mobility.

PMID- 16990227
TI  - Prescription of the first prosthesis and later use in children with congenital
      unilateral upper limb deficiency: A systematic review.
AB  - BACKGROUND: The prosthetic rejection rates in children with an upper limb
      transversal reduction deficiency are considerable. It is unclear whether the
      timing of the first prescription of the prosthesis contributes to the rejection
      rates. OBJECTIVE: To reveal whether scientific evidence is available in
      literature to confirm the hypothesis that the first prosthesis of children with
      an upper limb deficiency should be prescribed before two years of age. We expect
      lower rejection rates and better functional outcomes in children fitted at young
      age. METHODS: A computerized search was performed in several databases (Medline,
      Embase, Cinahl, Amed, Psycinfo, PiCarta and the Cochrane database). A combination
      of the following keywords and their synonyms was used: "prostheses, upper limb,
      upper extremity, arm and congenital". Furthermore, references of conference
      reports, references of most relevant studies, citations of most relevant studies
      and related articles were checked for relevancy. RESULTS: The search yielded 285
      publications, of which four studies met the selection criteria. The
      methodological quality of the studies was low. All studies showed a trend of
      lower rejection rates in children who were provided with their first prosthesis
      at less than two years of age. The pooled odds ratio of two studies showed a
      higher rejection rate in children who were fitted over two years of age (pooled
      OR = 3.6, 95% CI 1.6 - 8.0). No scientific evidence was found concerning the
      relation between the age at which a prosthesis was prescribed for the first time
      and functional outcomes. CONCLUSION: In literature only little evidence was found
      for a relationship between the fitting of a first prosthesis in children with a
      congenital upper limb deficiency and rejection rates or functional outcomes. As
      such, clinical practice of the introduction of a prosthesis is guided by clinical
      experience rather than by evidence-based medicine.

PMID- 16990228
TI  - The use of dynamic Lycra orthosis in the treatment of scoliosis: a case study.
AB  - Treatment of scoliosis has been under discussion in relation to surgical
      intervention since the Boston brace was presented by Hall in 1976 (Hall et al.
      1976; Watts et al. 1977). The effects of rigid bracing on thoracic skeletal
      integrity and the possible deformation of ribs due to the high localized pressure
      due to prolonged wear (Biorthex 1999; Coillard et al. 1999) have been
      highlighted. The lack of compliance (Houghton et al. 1987) has encouraged
      clinicians to investigate other options for non-surgical treatment. The Spinecor
      and Triac bracing systems have been developed as a result of this research;
      however, both of these orthoses had been designed with idiopathic scoliosis in
      mind. Little research has been done into the effects of bracing on the
      neuropathic curve. The use of dynamic Lycra garments in the treatment of
      neurological scoliosis offers the advantage of deformity correction without the
      bulk and discomfort of rigid braces. Recent clinical experience has shown that
      the Lycra suits have a positive effect in the treatment of scoliosis. This study
      discusses the treatment of a child presenting with a spinal tumour and although
      not truly of neurological presentation indicates that the garment can be used for
      the different scoliotic presentations.

PMID- 16990229
TI  - Clinical field testing of polyurethane feet for trans-tibial amputees in tropical
      low-income countries.
AB  - In a prospective controlled study, 172 polyurethane feet of different designs
      were fitted to 155 amputees with trans-tibial prostheses. These were followed in
      respect of their durability. The amputee compliance was in general good, and 87%
      were satisfied with their device. After 18 months the failure rate of 20% with
      the CIREC spring-blade foot was significantly better than the others, but poorer
      craftsmanship, higher complaint rate and lower compliance rate cast some doubt on
      the results. The results with the conventional SACH foot constructions with
      polyurethane as filling and covering materials were so poor after 18 months that
      their use cannot be recommended in tropical areas of the developing world.

PMID- 16990230
TI  - Clinical field testing of vulcanized rubber feet for trans-tibial amputees in
      tropical low-income countries.
AB  - In a prospective, controlled study, 186 prosthetic rubber feet of different
      designs were fitted to amputees with trans-tibial prostheses. There were 158
      amputees available for follow-up. The amputee compliance was good and 89% were
      satisfied with their device. After 18 months of use one VI-Solid rubber foot from
      VVAF in Cambodia had failed, as compared to 11% failures with the same foot with
      a heel cavity, 3% with the EB-1 sandwich construction from POF in Vietnam, all
      performing significantly better than the 62% encountered with the vulcanized
      rubber foot from ICRC in Cambodia; the latter representing half of the feet
      failing in amputees walking bare-footed. Nearly all failures were located at the
      foot-sole or the keel. The failure rate was 20% for the HI-Cambodia foot after 12
      months. After 24 months of use, still only one VI-Solid rubber foot had failed
      and this foot design was found superior to the others in regard of durability.

PMID- 16990231
TI  - A functional evaluation of prosthetic foot kinematics during lower-limb amputee
      gait.
AB  - This paper reports on a functional evaluation of prosthetic feet based on gait
      analysis. The aim is to analyse prosthetic feet behaviour under loads applied
      during gait in order to quantify user benefits for each foot. Ten traumatic
      amputees (six trans-tibial and four trans-femoral) were tested using their own
      prosthetic foot. An original protocol is presented to calculate the forefoot
      kinematics together with the overall body kinematics and ground reaction forces
      during gait. In this work, sagittal motion of the prosthetic ankle and the
      forefoot, time-distance parameters and ground reaction forces were examined. It
      is shown that an analysis of not only trans-tibial but also trans-femoral
      amputees provides an insight in the performance of prosthetic feet. Symmetry and
      prosthetic propulsive force were proved to be mainly dependant on amputation
      level. In contrast, the flexion of the prosthetic forefoot and several time
      distance parameters are highly influenced by foot design. Correlations show
      influential of foot and ankle kinematics on other parameters. These results
      suggest that prosthetic foot efficiency depends simultaneously on foot design and
      gait style. The evaluation, proposed in this article, associated to clinical
      examination should help to achieve the best prosthetic foot match to a patient.

PMID- 16990232
TI  - The role of Mothers Against Drunk Driving (MADD) in reducing alcohol-related
      crashes in the U.S.

PMID- 16990233
TI  - Mothers Against Drunk Driving (MADD): the first 25 years.
AB  - Mothers Against Drunk Driving (MADD) has arguably been one of the most successful
      public-health grassroots citizen advocacy organizations in the United States in
      the past century. In 2005, MADD celebrated the 25th anniversary of its founding.
      Based on a national poll by the Gallup Organization in 2005, MADD is recognized
      by 94% of citizens. It is generally given credit for changing American attitudes
      toward drinking and driving. Since MADD's founding in 1980, alcohol-related
      traffic deaths in the United States have decreased from an estimated 30,000 to
      16,694 in 2004, according to the National Highway Traffic Safety Administration.
      This article examines the growth of MADD since its founding and attempts to gauge
      its contribution to the public's understanding of the impaired-driving problem
      and to the reductions in alcohol-related highway deaths and injuries that have
      occurred in the first 25 years of its existence.

PMID- 16990234
TI  - Low-manpower checkpoints: can they provide effective DUI enforcement in small
      communities?
AB  - OBJECTIVE: Sobriety checkpoints can be effective in reducing alcohol-impaired
      driving. Checkpoints are underutilized, however, partially because police believe
      a large number of officers are required. This study evaluated the feasibility and
      impact of conducting small-scale checkpoints in rural communities. METHODS: Law
      enforcement agencies in two counties agreed to conduct weekly checkpoints for one
      year. Two nonadjacent counties did not undertake additional checkpoints.
      Evaluation included public-awareness surveys and roadside surveys (including
      blood alcohol concentration [BAC] measurements) of weekend nighttime drivers.
      RESULTS: Relative to drivers in the comparison counties, the proportion of
      drivers in the experimental counties with BACs >0.05% was 70% lower. Drivers
      surveyed at driver's license offices in the experimental counties after program
      implementation were more likely to report seeing or passing through a checkpoint
      and were more aware of publicity on driving under the influence (DUI)
      enforcement. CONCLUSIONS: Small rural communities can safely and effectively
      conduct low-staff sobriety checkpoints on a weekly basis. Such programs can be
      expected to result in large reductions in drivers operating at higher BACs.

PMID- 16990235
TI  - Driver's alcohol and passenger's death in motor vehicle crashes.
AB  - OBJECTIVE: Previous studies on alcohol involvement associated with fatal injury
      in traffic crashes have focused on the drivers, but the passenger's view is not
      well known. This study (1) analyzes the relationship between passenger's death
      and alcohol inebriation of the driver and (2) estimates the role of alcohol as
      the cause of a crash by examining who was at fault, sober, or inebriated. METHOD:
      The study includes all motor vehicle passengers (n = 420) who died in crashes in
      Sweden 1993 through 1996 and were medicolegally autopsied. Autopsy reports from
      the Departments of Forensic Medicine, including toxicological analyses, and
      police reports were studied. Presence of alcohol among drivers was based on blood
      and breath tests. RESULTS: One-fifth of the fatally injured passengers and one
      fifth of the tested drivers were under the influence of alcohol. The youngest
      drivers had the highest prevalence of drunken driving. Drivers at fault were
      alcohol positive in 21% of these crashes and drivers were not at fault in 2% of
      these crashes. In 53% of the crashes where both the passenger and driver were
      alcohol positive, the passenger had a lower alcohol concentration than the
      driver. Children (<16 years) comprised 15% of the killed passengers. Notably, the
      children were riding with a driver who was under influence of alcohol in 13% of
      these crashes. Alcohol involvement was not tested in half of the surviving
      drivers. CONCLUSIONS: The data show that 20% of both passengers and drivers were
      under the influence of alcohol. Increased testing of surviving drivers regarding
      alcohol and other drugs is recommended.

PMID- 16990236
TI  - Parental supervision of teenage drivers in a graduated licensing system.
AB  - OBJECTIVES: Most states now have lengthy learner periods for young, beginning
      drivers as part of their graduated driver licensing (GDL) systems. Although
      parents play a vital role during the learner stage of GDL by supervising driving
      practice, virtually nothing is known about the nature and quality of parental
      supervision. The objectives of this study were to investigate parents'
      supervisory behavior and parent-teen relationships during the learner stage of
      graduated licensing and to evaluate two approaches for assisting parents in
      supervising their teenager's early driving experience. METHODS: Families of
      teenagers applying for a learner permit received either a booklet describing
      highly structured practice sessions for beginning drivers, a series of "tip
      sheets" offering more generalized guidance, or no special materials.
      Questionnaires were sent separately to parents and teenagers three to six months
      after teenagers obtained their permit. RESULTS: Of 1,190 participating families,
      653 parents (55%) and 609 teenagers (51%) responded. Both parents and teenagers
      perceived parents as supportive and helpful during driving sessions. Parents
      often demonstrated positive behaviors, such as complimenting their teenager and
      pointing out possible hazards; they also exhibited less desirable behaviors, such
      as raising their voice, but these were less frequent. A majority of parents (71%)
      and teenagers (52%) reported that they enjoyed spending this time together. About
      four months after obtaining a permit, most parents believed their teenager did
      not yet have enough experience and was not ready to drive unsupervised. Although
      the reported behaviors are encouraging, within-family agreement was low on most
      items. Finally, efforts to assist parents proved unsuccessful. Although parents
      thought the booklet and tip sheets were helpful, most used these materials only
      in a general way. CONCLUSIONS: The extended learning experience required by GDL
      programs is a positive experience for many families. However, finding a method
      for helping parents achieve maximum benefits during this process will be
      challenging. The results also suggest that current requirements in the learner
      phase of most state GDL systems (six months; 30-50 hours) may be inadequate to
      ensure that teenagers obtain a sufficient amount of experience to begin driving
      safely on their own.

PMID- 16990237
TI  - Driving circumstances and accidents among novice drivers.
AB  - OBJECTIVE: The study evaluated the accident risk of certain driving circumstances
      and driving motives among novice drivers. METHODS: Self-reported exposure and
      accidents according to driving circumstances and driving motives were compared
      between young (n = 6,847) and middle-aged (n = 942) male and female novice
      drivers. For young drivers, self-reported accidents were further compared to
      fatal accidents (n = 645) in terms of the driving conditions in which they
      occurred. The survey was conducted in 2002 and the questions regarding the
      quantity and quality of driving exposure and accidents covered the first four
      years of the novice drivers' driving career after licensing. Data on fatal
      accidents related to the period of 1990 to 2000. RESULTS: Leisure-time driving,
      driving just for fun, and driving with passengers and during evenings and at
      night was more typical for young drivers than for middle-aged drivers. For middle
      aged drivers, the most typical driving was driving to or from work. Driving on
      errands was more typical for females than males. Nighttime driving was
      overrepresented in young drivers' self-reported and fatal accidents, compared to
      the share of young drivers' driving at night. Slippery road conditions were over
      represented in young male drivers' self-reported accidents, but not in their
      fatal accidents, whereas for young females slippery road conditions seemed to
      increase the propensity of fatal accidents. CONCLUSIONS: The study concluded that
      some driving conditions increase the risk of certain types of accidents among
      certain driver groups, but not among all drivers. For example, slippery road
      conditions were overrepresented in young male drivers' minor (self-reported)
      accidents, but not in their fatal accidents. For young female drivers slippery
      road conditions seem to increase the propensity of fatal accidents. Driving
      circumstances are different in minor (self-reported) and fatal accidents. When
      drawing conclusions regarding accident risk, it is important to determine the
      seriousness of the accidents which take place.

PMID- 16990238
TI  - Do recommended driving limits affect teen-reported traffic violations and crashes
      during the first 12 months of independent driving?
AB  - OBJECTIVES: Motor vehicle crashes are highly elevated among newly licensed
      teenage drivers. Limits on high-risk driving conditions by driver licensing
      policies and parents can protect novice teens from negative driving outcomes,
      while they experience and driving proficiency. The purpose of this research was
      to evaluate the effects of strict parent-imposed driving limits on driving
      outcomes during the first year of licensure. METHODS: A sample of 3,743
      Connecticut teens was recruited and randomized to the Checkpoints Program or
      comparison condition. Assessments conducted at baseline, licensure, 3-, 6-, and
      12-months postlicensure included parent-imposed driving limits, traffic
      violations, and crashes. Bivariate and multivariate analyses were conducted to
      assess the effects of strict parent limits on traffic violations and crashes
      during the first year of licensure. RESULTS: Thirty percent of teens reported at
      least one traffic violation and 40% reported at least one crash. More strict
      parent-imposed limits at licensure, 3-, 6-, and 12-months postlicensure, were
      associated with fewer violations and crashes in multivariate analyses. Notably,
      adherence to recommended night curfew was consistently associated with fewer
      violations and crashes. CONCLUSIONS: The findings indicate that strict parent
      imposed limits may protect novice teen drivers from negative driving outcomes.

PMID- 16990239
TI  - Characteristics and risks of drivers with low annual distance driven.
AB  - OBJECTIVES: It has been noted by several authors that risk (defined only in terms
      of total expected numbers of crash involvements per total distance driven) paints
      a misleading picture of crash liability, particularly for the young and the old,
      as their high risk is associated with risky driving patterns typical of people
      who drive low annual kms. This article sets out to analyze these driving patterns
      of low-km drivers and to evaluate the risk of these patterns. As licensing
      programs tend to focus on young and old drivers, who tend to drive lower annual
      distances, income and employment data are also analyzed for low-km drivers. This
      is to provide a better picture for policy makers of the sort of people and the
      sorts of transportation requirements that their policies may affect. METHODS:
      Crash data and travel data were disaggregated by driver characteristics and by
      driving conditions (road type, day and night, weekend and weekday) and combined
      to form estimates of risk for typical driving patterns of driver groups.
      Characteristics of driving patterns and of the drivers themselves were derived
      for groups defined by age and by the amount of annual driving undertaken.
      RESULTS: Older drivers who drive less tend to have higher risk per km mainly due
      to their predominantly urban trips. Nevertheless, because older drivers on
      average manage to reduce their risk per distance driven by choosing driving
      patterns that are safer than the driving patterns of other age groups, the risk
      of older drivers as a group is not overestimated. CONCLUSION: Despite being quite
      different from one another, the low- and high-km driving patterns of younger
      drivers were found to impose identical risks.

PMID- 16990240
TI  - Motor vehicle restraint system use and risk of spine injury.
AB  - OBJECTIVE: Motor vehicle collision (MVC)-related spinal injury is a severe and
      often permanently disabling injury. In addition, strain injuries have been
      reported as a common outcome of MVCs. Although advances in automobile
      crashworthiness have reduced both fatalities and severe injuries, the impact of
      varying occupant restraint systems (seatbelts and airbags) on thoracolumbar spine
      injuries is unknown. This study examined the relationship between the occurrence
      of mild to severe cervical and thoracolumbar spine injury and occupant restraint
      systems among front seat occupants involved in frontal MVCs. METHODS: A
      retrospective cohort study was conducted among subjects obtained from the 1995
      2004 National Automotive Sampling System. Cases were identified based on having
      sustained a spine injury of >/=1 on the Abbreviated Injury Scale (AIS), 1990
      Revision. Risk risks (RRs) and 95% confidence intervals (CIs) were computed
      comparing occupant restraint systems with unrestrained occupants. RESULTS: We
      found an overall incidence of AIS1 cervical (11.8%) and thoracolumbar (3.7%)
      spinal injury. Seatbelt only restraints were associated with increased cervical
      AIS1 injury (RR = 1.40, 95% CI 1.04-1.88). However, seatbelt only restraints
      showed the greatest risk reduction for AIS2 spinal injuries. Airbag only
      restraints reduced thoracolumbar AIS1 injuries (RR = 0.29, 95% CI 0.08-1.04).
      Seatbelt combined with airbag use was protective for cervical AIS3+ injury
      overall (RR = 0.29, 95% CI 0.14-0.58), cervical neurological injury (RR = 0.19,
      95% CI 0.05-0.81), and thoracolumbar AIS3+ injury overall (RR = 0.20, 95% CI 0.05
      0.70). CONCLUSIONS: The results of this study suggest that seatbelts alone or in
      combination with an airbag increased the incidence of AIS1 spinal injuries, but
      provide protection against more severe injury to all regions of the spine. Airbag
      deployment without seatbelt use did not show increased protection relative to
      unrestrained occupants.

PMID- 16990241
TI  - Predicting multiplanar cervical spine injury due to head-turned rear impacts
      using IV-NIC.
AB  - OBJECTIVE: Intervertebral Neck Injury Criterion (IV-NIC) hypothesizes that
      dynamic three-dimensional intervertebral motion beyond physiological limit may
      cause multiplanar soft-tissue injury. Present goals, using biofidelic whole human
      cervical spine model with muscle force replication and surrogate head in head
      turned rear impacts, were to: (1) correlate IV-NIC with multiplanar injury, (2)
      determine IV-NIC injury threshold at each intervertebral level, and (3) determine
      time and mode of dynamic intervertebral motion that caused injury. METHODS:
      Impacts were simulated at 3.5, 5, 6.5, and 8 g horizontal accelerations of T1
      vertebra (n = 6; average age: 80.2 years; four male, two female donors). IV-NIC
      was defined at each intervertebral level and in each motion plane as dynamic
      intervertebral rotation divided by physiological limit. Three-plane pre- and post
      impact flexibility testing measured soft-tissue injury; that is significant
      increase in neutral zone (NZ) or range of motion (RoM) at any intervertebral
      level, above baseline. IV-NIC injury threshold was average IV-NIC peak at injury
      onset. RESULTS: IV-NIC extension peaks correlated best with multiplanar injuries
      (P < 0.001): extension RoM (R = 0.55) and NZ (R = 0.42), total axial rotation RoM
      (R = 0.42) and NZ (R = 0.41), and total lateral bending NZ (R = 0.39). IV-NIC
      injury thresholds ranged between 1.1 at C0-C1 and C3-C4 to 2.9 at C7-T1. IV-NIC
      injury threshold times were attained between 83.4 and 150.1 ms following impact.
      CONCLUSIONS: Correlation between IV-NIC and multiplanar injuries demonstrated
      that three-plane intervertebral instability was primarily caused by dynamic
      extension beyond the physiological limit during head-turned rear impacts.

PMID- 16990242
TI  - Analyses of rear-end crashes based on classification tree models.
AB  - OBJECTIVE: Signalized intersections are accident-prone areas especially for rear
      end crashes due to the fact that the diversity of the braking behaviors of
      drivers increases during the signal change. The objective of this article is to
      improve knowledge of the relationship between rear-end crashes occurring at
      signalized intersections and a series of potential traffic risk factors
      classified by driver characteristics, environments, and vehicle types. METHODS:
      Based on the 2001 Florida crash database, the classification tree method and
      Quasi-induced exposure concept were used to perform the statistical analysis. Two
      binary classification tree models were developed in this study. One was used for
      the crash comparison between rear-end and non-rear-end to identify those specific
      trends of the rear-end crashes. The other was constructed for the comparison
      between striking vehicles/drivers (at-fault) and struck vehicles/drivers (not-at
      fault) to find more complex crash pattern associated with the traffic attributes
      of driver, vehicle, and environment. RESULTS: The modeling results showed that
      the rear-end crashes are over-presented in the higher speed limits (45-55 mph);
      the rear-end crash propensity for daytime is apparently larger than nighttime;
      and the reduction of braking capacity due to wet and slippery road surface
      conditions would definitely contribute to rear-end crashes, especially at
      intersections with higher speed limits. The tree model segmented drivers into
      four homogeneous age groups: < 21 years, 21-31 years, 32-75 years, and > 75
      years. The youngest driver group shows the largest crash propensity; in the 21-31
      age group, the male drivers are over-involved in rear-end crashes under adverse
      weather conditions and the 32-75 years drivers driving large size vehicles have a
      larger crash propensity compared to those driving passenger vehicles.
      CONCLUSIONS: Combined with the quasi-induced exposure concept, the classification
      tree method is a proper statistical tool for traffic-safety analysis to
      investigate crash propensity. Compared to the logistic regression models, tree
      models have advantages for handling continuous independent variables and easily
      explaining the complex interaction effect with more than two independent
      variables. This research recommended that at signalized intersections with higher
      speed limits, reducing the speed limit to 40 mph efficiently contribute to a
      lower accident rate. Drivers involved in alcohol use may increase not only rear
      end crash risk but also the driver injury severity. Education and enforcement
      countermeasures should focus on the driver group younger than 21 years. Further
      studies are suggested to compare crash risk distributions of the driver age for
      other main crash types to seek corresponding traffic countermeasures.

PMID- 16990243
TI  - Turning at intersections and pedestrian injuries.
AB  - OBJECTIVE: To evaluate if precrash vehicle movement is associated with the
      severity of pedestrian injury. METHODS: We used comprehensive information on
      pedestrian, vehicle, and injury-related characteristics gathered in the
      Pedestrian Crash Data Study (PCDS), conducted by the National Highway Traffic
      Safety Administration (NHTSA) (1994-1998). The odds ratio of severe injuries
      (injury severity score >/= 15) and crash fatality rate for right- and left-turn
      collisions at intersection compared with straight vehicle movement were compared
      using a logistic regression model and taking into consideration the type of
      vehicle and age of the pedestrians as potential effect modifiers. Later we
      evaluated the intermediate effect of impact speed on the association by adding it
      to the logistic regression model. RESULTS: Of 255 collisions eligible for this
      analysis, the proportion of pedestrian hit during straight movement, right turns,
      and left turns were 48%, 32%, and 10%, respectively. Sixty percent of the
      pedestrians in left-turn crashes and 67% of them in right-turn collisions were
      hit from their left side. For straight movements the pedestrians were equally
      likely to be struck beginning from the left or right side of the street. After
      adjustment for pedestrian's age, vehicle movement was a significant predictor of
      severe injuries (p < 0.0001) and case fatality (p = 0.003). The association
      between vehicle precrash movement and severe injuries (p = 0.551) and case
      fatality (p = 0.912) vanished after adjusting for impact speed. This indicated
      that the observed association was probably the result of the difference in impact
      speed and not the precrash movement of the vehicle. CONCLUSION: Pedestrian safety
      interventions that aim at environmental modifications, such as crosswalk
      repositioning, might be the most efficient means in reducing right- or left-turn
      collisions at intersection, while pedestrians' behavioral modifications should be
      the priority for alleviating the magnitude of the collisions that happen in
      vehicles' straight movements.

PMID- 16990244
TI  - Influence of age-related stature on the frequency of body region injury and
      overall injury severity in child pedestrian casualties.
AB  - OBJECTIVE: The current study aims to evaluate the influence of age-related
      stature on the frequency of body region injury and overall injury severity in
      children involved in pedestrian versus motor vehicle collisions (PMVCs). METHODS:
      A trauma registry including the coded injuries sustained by 1,590 1- to 15-year
      old pedestrian casualties treated at a level-one trauma center was categorized by
      stature-related age (1-3, 4-6, 7-9, 10-12, and 13-15 years) and body region (head
      and face, neck, thorax, abdomen and pelvic content, thoracic and lumbar spine,
      upper extremities, pelvis, and lower extremities). The lower extremity category
      was further divided into three sub-structures (thigh, leg, and knee). For each
      age group and body region/sub-structure the proportion of casualties with at
      least one injury was then determined at given Abbreviated Injury Scale (AIS)
      severity levels. In addition, the average and distribution of the Maximum
      Abbreviated Injury Score (MAIS) and the average Injury Severity Score (ISS) were
      determined for each age group. The calculated proportions, averages, and
      distributions were then compared between age groups using appropriate
      significance tests. RESULTS: The overall outcome showed relatively minor
      variation between age groups, with the average +/- SD MAIS and ISS ranging from
      2.3 +/- 0.9 to 2.5 +/- 1.0 and 8.2 +/- 7.2 to 9.4 +/- 8.9, respectively. The
      subjects in the 1- to 3-year-old age group were more likely to sustain injury to
      the head, face, and torso regions than the older subjects. The frequency of AIS
      2+ lower extremity injury was approximately 20% in the 1- to 3-year-old group,
      but was twice as high in the 4- to 12-years age range and 2.5 times as high in
      the oldest age group. The frequency of femur fracture increased from 10% in the
      youngest group to 26% in the 4- to 6-year-old group and then declined to 14% in
      the 10- to 15-years age range. The frequency of tibia/fibula fracture increased
      monotonically with group age from 8% in the 1- to 3-year-old group to 31% in the
      13- to 15-year-old group. CONCLUSIONS: While the overall outcome of child
      pedestrian casualties appears to be relatively constant across the pediatric
      stature range considered ( approximately 74-170 cm), subject height seems to
      affect the frequency of injury to individual body regions, including the thorax
      and lower extremities. This suggests that vehicle safety designers need not only
      account for the difference in injury patterns between adult and pediatric
      pedestrian casualties, but also for the variation within the pediatric group.

PMID- 16990245
TI  - Development of injury criteria for pelvic fracture in frontal crashes.
AB  - OBJECTIVE: This article assesses the position-dependent injury tolerance of the
      hip in the frontal direction based on testing of eight postmortem human subjects.
      METHODS: For each subject, the left and right hemipelvis complex was axially
      loaded using a previously developed test configuration. Six positions were
      defined from a seated femur neutral condition, combining flexed, neutral, and
      extended femur positions with abducted, neutral, and adducted positions. RESULTS:
      Axial injury tolerances based on peak force were found to be 6,850 +/- 840 N in
      the extended, neutral position and 4,080 +/- 830 N in the flexed, neutral
      position. From the flexed neutral orientation, the peak axial force increased 18%
      for 20 degrees abduction and decreased 6% for 20 degrees adduction. From the
      extended, neutral orientation, the peak axial force decreased 4% for 20 degrees
      abduction and decreased 3% for 20 degrees adduction. However, as there is
      evidence that increases in loading may occur after the initiation of fracture,
      the magnitude of the peak force is likely related to the extent of injury, not to
      the initial tolerance. Using the axial femur force at the initiation of fracture
      (assessed with acoustic crack sensors) as a potentially more relevant indicator
      of injury may lower the existing injury criteria. This fracture initiation force
      varied by position from 3,010 +/- 560 N in the flexed, neutral position to 5,470
      N in the extended, abducted position. Further, there was a large position
      dependent variation in the ratio of fracture initiation force to the peak axial
      force. The initiation of fracture was 83% of the peak axial force in the
      extended, abducted position, but the ratio was 34% in the extended, adducted
      position. CONCLUSIONS: This may have significant implications for the development
      of pelvic injury criteria by automobile designers attempting to mitigate pelvis
      injuries.

PMID- 16990246
TI  - Recovering motifs from biased genomes: application of signal correction.
AB  - A significant problem in biological motif analysis arises when the background
      symbol distribution is biased (e.g. high/low GC content in the case of DNA
      sequences). This can lead to overestimation of the amount of information encoded
      in a motif. A motif can be depicted as a signal using information theory (IT). We
      apply two concepts from IT, distortion and patterned interference (a type of
      noise), to model genomic and codon bias respectively. This modeling approach
      allows us to correct a raw signal to recover signals that are weakened by
      compositional bias. The corrected signal is more likely to be discriminated from
      a biased background by a macromolecule. We apply this correction technique to
      recover ribosome-binding site (RBS) signals from available sequenced and
      annotated prokaryotic genomes having diverse compositional biases. We observed
      that linear correction was sufficient for recovering signals even at the extremes
      of these biases. Further comparative genomics studies were made possible upon
      correction of these signals. We find that the average Euclidian distance between
      RBS signal frequency matrices of different genomes can be significantly reduced
      by using the correction technique. Within this reduced average distance, we can
      find examples of class-specific RBS signals. Our results have implications for
      motif-based prediction, particularly with regards to the estimation of reliable
      inter-genomic model parameters.

PMID- 16990247
TI  - snoSeeker: an advanced computational package for screening of guide and orphan
      snoRNA genes in the human genome.
AB  - Small nucleolar RNAs (snoRNAs) represent an abundant group of non-coding RNAs in
      eukaryotes. They can be divided into guide and orphan snoRNAs according to the
      presence or absence of antisense sequence to rRNAs or snRNAs. Current snoRNA
      searching programs, which are essentially based on sequence complementarity to
      rRNAs or snRNAs, exist only for the screening of guide snoRNAs. In this study, we
      have developed an advanced computational package, snoSeeker, which includes
      CDseeker and ACAseeker programs, for the highly efficient and specific screening
      of both guide and orphan snoRNA genes in mammalian genomes. By using these
      programs, we have systematically scanned four human-mammal whole-genome alignment
      (WGA) sequences and identified 54 novel candidates including 26 orphan candidates
      as well as 266 known snoRNA genes. Eighteen novel snoRNAs were further
      experimentally confirmed with four snoRNAs exhibiting a tissue-specific or
      restricted expression pattern. The results of this study provide the most
      comprehensive listing of two families of snoRNA genes in the human genome till
      date.

PMID- 16990248
TI  - Utilising the left-helical conformation of L-DNA for analysing different marker
      types on a single universal microarray platform.
AB  - L-DNA is the perfect mirror-image form of the naturally occurring d-conformation
      of DNA. Therefore, L-DNA duplexes have the same physical characteristics in terms
      of solubility, duplex stability and selectivity as D-DNA but form a left-helical
      double-helix. Because of its chiral difference, L-DNA does not bind to its
      naturally occurring D-DNA counterpart, however. We analysed some of the
      properties that are typical for L-DNA. For all the differences, L-DNA is
      chemically compatible with the D-form of DNA, so that chimeric molecules can be
      synthesized. We take advantage of the characteristics of L-DNA toward the
      establishment of a universal microarray that permits the analysis of different
      kinds of molecular diagnostic information in a single experiment on a single
      platform, in various combinations. Typical results for the measurement of
      transcript level variations, genotypic differences and DNA-protein interactions
      are presented. However, on the basis of the characteristic features of L-DNA,
      also other applications of this molecule type are discussed.

PMID- 16990249
TI  - The different cleavage DNA sequence specificity explains the camptothecin
      resistance of the human topoisomerase I Glu418Lys mutant.
AB  - Yeast cells expressing the Glu418Lys human topoisomerase I mutant display a
      camptothecin resistance that slowly decreases as a function of time. Molecular
      characterization of the single steps of the catalytic cycle of the purified
      mutant indicates that it has a relaxation activity identical to the wild-type
      protein but a different DNA sequence specificity for the cleavage sites when
      compared to the wild-type enzyme, as assayed on several substrates. In particular
      the mutant has a low specificity for CPT sensitive cleavable sites. In fact, the
      mutant has, at variance of the wild-type enzyme, a reduced preference for
      cleavage sites having a thymine base in position -1 of the scissile strand. This
      preference, together with the strict requirement for a thymine base in position 
      1 for an efficient camptothecin binding, explains the temporary camptothecin
      resistance of the yeast cell expressing the mutant and points out the importance
      of the DNA sequence in the binding of the camptothecin drug.

PMID- 16990250
TI  - RAD51AP2, a novel vertebrate- and meiotic-specific protein, shares a conserved
      RAD51-interacting C-terminal domain with RAD51AP1/PIR51.
AB  - Many interacting proteins regulate and/or assist the activities of RAD51, a
      recombinase which plays a critical role in both DNA repair and meiotic
      recombination. Yeast two-hybrid screening of a human testis cDNA library revealed
      a new protein, RAD51AP2 (RAD51 Associated Protein 2), that interacts strongly
      with RAD51. A full-length cDNA clone predicts a novel vertebrate-specific protein
      of 1159 residues, and the RAD51AP2 transcript was observed only in meiotic tissue
      (i.e. adult testis and fetal ovary), suggesting a meiotic-specific function for
      RAD51AP2. In HEK293 cells the interaction of RAD51 with an ectopically-expressed
      recombinant large fragment of RAD51AP2 requires the C-terminal 57 residues of
      RAD51AP2. This RAD51-binding region shows 81% homology to the C-terminus of
      RAD51AP1/PIR51, an otherwise totally unrelated RAD51-binding partner that is
      ubiquitously expressed. Analyses using truncations and point mutations in both
      RAD51AP1 and RAD51AP2 demonstrate that these proteins use the same structural
      motif for RAD51 binding. RAD54 shares some homology with this RAD51-binding
      motif, but this homologous region plays only an accessory role to the adjacent
      main RAD51-interacting region, which has been narrowed here to 40 amino acids. A
      novel protein, RAD51AP2, has been discovered that interacts with RAD51 through a
      C-terminal motif also present in RAD51AP1.

PMID- 16990251
TI  - Multiple pathways regulate intracellular shuttling of MoKA, a co-activator of
      transcription factor KLF7.
AB  - MoKA is a novel F-box containing protein that interacts with and stimulates the
      activity of transcription factor KLF7, a regulator of neuronal differentiation.
      MoKA accumulates throughout the cell and predominantly in the cytosol, consistent
      with the presence of several putative nuclear localization and export signals
      (NLSs and NESs). The present study was designed to refine the identity and
      location of the sequences responsible for MoKA intracellular shuttling and
      transcriptional activity. Forced expression of fusion proteins in mammalian cells
      demonstrated that only one of three putative NLSs potentially recognized by
      karyopherin receptors is involved in nuclear localization of MoKA. By contrast,
      three distinct sequences were found to participate in mediating cytoplasmic
      accumulation. One of them is structurally and functionally related to the leucine
      rich export signal that interacts with the exportin 1 (CRM1) receptor. The other
      two export signals instead display either a novel leucine-rich sequence or an
      undefined peptide motif, and both appear to act through CRM1-independent
      pathways. Finally, transcriptional analyses using the chimeric GAL4 system mapped
      the major activation domain of MoKA to a highly acidic sequence that resides
      between the NLS and NES clusters.

PMID- 16990252
TI  - Interplay of Fli-I and FLAP1 for regulation of beta-catenin dependent
      transcription.
AB  - Beta-catenin mediates Wnt/wingless signaling and transcriptional activation by
      lymphocyte enhancer binding factor 1/T cell factor (LEF1/TCF) proteins with the
      assistance of multiple coregulators, including positive cofactors like p300/CBP
      and negative cofactors like HDACs. We previously demonstrated that a
      developmentally essential protein, Flightless-I (Fli-I), serves as a coactivator
      for nuclear receptor-mediated transcription. To further understand the action
      mechanism of Fli-I, we investigated the functional roles of Fli-I and Fli-I
      leucine rich repeat associated protein 1 (FLAP1) in transcriptional activation by
      beta-catenin and LEF1/TCF. beta-catenin-dependent transcription was activated by
      exogenous FLAP1 but inhibited by Fli-I. Reduction of endogenous FLAP1 levels
      compromised transcriptional activation by LEF1/TCF, beta-catenin and the p160
      coactivator GRIP1. FLAP1 interacted directly with beta-catenin, GRIP1 and p300
      and enhanced their activity. Furthermore, FLAP1 was strongly synergistic with
      p300 in supporting transcriptional activation by beta-catenin and LEF1/TCF, but
      Fli-I disrupted the synergy of FLAP1 with p300 and beta-catenin. Thus the
      opposing effects of Fli-I and FLAP1 may be a key regulatory mechanism for beta
      catenin and LEF1/TCF-mediated transcription and thus for Wnt signaling, and some
      mutations of Fli-I may result in developmental defects, such as the flightless
      phenotype of Drosophila, by causing dysregulation of the Wnt/beta-catenin
      pathway.

PMID- 16990253
TI  - Controlling the rate of organic reactions: rational design of allosteric Diels
      Alderase ribozymes.
AB  - Allosteric mechanisms are widely used in nature to control the rates of enzymatic
      reactions, but little is known about RNA catalysts controlled by these
      principles. The only natural allosteric ribozyme reported to date catalyzes an
      RNA cleavage reaction, and so do almost all artificial systems. RNA has, however,
      been shown to accelerate a much wider range of chemical reactions. Here we report
      that RNA catalysts for organic reactions can be put under the stringent control
      of effector molecules by straight-forward rational design. This approach uses
      known RNA sequences with catalytic and ligand-binding properties, and exploits
      weakly conserved sequence elements and available structural information to induce
      the formation of alternative, catalytically inactive structures. The potential
      and general applicability is demonstrated by the design of three different
      systems in which the rate of a catalytic carbon-carbon bond forming reaction is
      positively regulated up to 2100-fold by theophylline, tobramycin and a specific
      mRNA sequence, respectively. Although smaller in size than a tRNA, all three
      ribozymes show typical features of allosteric metabolic enzymes, namely high rate
      acceleration and tight allosteric regulation. Not only do these findings
      demonstrate RNA's power as a catalyst, but also highlight on RNA's capabilities
      as signaling components in regulatory networks.

PMID- 16990254
TI  - High fidelity of RecA-catalyzed recombination: a watchdog of genetic diversity.
AB  - Homologous recombination plays a key role in generating genetic diversity, while
      maintaining protein functionality. The mechanisms by which RecA enables a single
      stranded segment of DNA to recognize a homologous tract within a whole genome are
      poorly understood. The scale by which homology recognition takes place is of a
      few tens of base pairs, after which the quest for homology is over. To study the
      mechanism of homology recognition, RecA-promoted homologous recombination between
      short DNA oligomers with different degrees of heterology was studied in vitro,
      using fluorescence resonant energy transfer. RecA can detect single mismatches at
      the initial stages of recombination, and the efficiency of recombination is
      strongly dependent on the location and distribution of mismatches. Mismatches
      near the 5' end of the incoming strand have a minute effect, whereas mismatches
      near the 3' end hinder strand exchange dramatically. There is a characteristic
      DNA length above which the sensitivity to heterology decreases sharply.
      Experiments with competitor sequences with varying degrees of homology yield
      information about the process of homology search and synapse lifetime. The
      exquisite sensitivity to mismatches and the directionality in the exchange
      process support a mechanism for homology recognition that can be modeled as a
      kinetic proofreading cascade.

PMID- 16990255
TI  - ZBP1 subcellular localization and association with stress granules is controlled
      by its Z-DNA binding domains.
AB  - Z-DNA binding protein 1 (ZBP1) belongs to a family of proteins that contain the
      Zalpha domain, which binds specifically to left-handed Z-DNA and Z-RNA. Like all
      vertebrate proteins in the Zalpha family, it contains two Zalpha-like domains and
      is highly inducible by immunostimulation. Using circular dichroism spectroscopy
      and electrophoretic mobility shift assays we show that both Zalpha domains can
      bind Z-DNA independently and that substrate binding is greatly enhanced when both
      domains are linked. Full length ZBP1 and a prominent splice variant lacking the
      first Zalpha domain (DeltaZalpha) showed strikingly different subcellular
      localizations. While the full length protein showed a finely punctate
      cytoplasmatic distribution, ZBP1DeltaZalpha accumulated in large cytoplasmic
      granules. Mutation of residues important for Z-DNA binding in the first Zalpha
      domain resulted in a distribution comparable to that of ZBP1DeltaZalpha. The
      ZBP1DeltaZalpha granules are distinct from stress granules (SGs) and processing
      bodies but dynamically interacted with these. Polysome stabilization led to the
      disassembly of ZBP1DeltaZalpha granules, indicating that mRNA are integral
      components. Heat shock and arsenite exposure had opposing effects on ZBP1
      isoforms: while ZBP1DeltaZalpha granules disassembled, full length ZBP1
      accumulated in SGs. Our data link ZBP1 to mRNA sorting and metabolism and
      indicate distinct roles for ZBP1 isoforms.

PMID- 16990257
TI  - Novel iso-branched ether lipids as specific markers of developmental sporulation
      in the myxobacterium Myxococcus xanthus.
AB  - Iso-fatty acids (FAs) are the dominant FA family in all myxobacteria analyzed.
      Furthermore, it was postulated that iso-FAs or compounds derived thereof are
      involved in fruiting body formation in Myxococcus xanthus, since mutants with a
      reduced level of iso-FA due to a reduced level of the precursor isovaleryl-CoA,
      are delayed in aggregation and produce only few myxospores. To elucidate the
      function of iso-FAs and their corresponding lipids we have analyzed the
      developmental phenotype of mutants having different levels of iso-FAs resulting
      in a clear correlation between the amount of iso-FAs and the delay of aggregation
      and reduction in spore yield. Addition of either isovalerate or 13
      methyltetradecanoic acid resulted in restoration of the wild-type FA profile and
      normal development. Detailed analysis of the fatty acid (FA) profile during
      fruiting body formation in Myxococcus xanthus wild-type revealed the specific
      accumulation of 13-methyltetradecanal and 1-O-13-methyltetradecylglycerol which
      were produced specifically in the myxospores and which are derived from 1-O-(13
      methyl-1-Z-tetradecenyl)-2-O-(13-methyltetradecanoyl)-glycero-3
      phosphatidylethanolamine (VEPE) and 1,2-di-(13-methyltetradecanoyl)-3-(13
      methyltetradecyl)glycerol (TG-1), respectively. The structures of these unusual
      ether lipids have been determined by spectrometric methods and synthesis (for TG
      1). Analysis of several mutants blocked at different stages of development
      indicated that the biosynthesis of TG-1 is developmentally regulated and that
      VEPE might be an intermediate in the TG-1 biosynthesis. Finally, addition of TG-1
      to mutants blocked in the biosynthesis of isovaleryl-CoA could restore
      aggregation and sporulation emphasizing the important role of iso-branched lipids
      for myxobacterial development.

PMID- 16990256
TI  - Critical role of vimentin phosphorylation at Ser-56 by p21-activated kinase in
      vimentin cytoskeleton signaling.
AB  - Phosphorylation and spatial reorganization of the vimentin network have been
      implicated in mediating smooth muscle contraction, cell migration, and mitosis.
      In this study, stimulation of cultured smooth muscle cells with 5
      hydroxytryptamine (5-HT) induced PAK1 phosphorylation at Thr-423 (an indication
      of p21-activated kinase (PAK) activation). Treatment with PAK led to disassembly
      of wild-type (but not mutant S56A) vimentin filaments as assessed by an in vitro
      filament assembly assay. Furthermore, stimulation with 5-HT resulted in the
      dissociation of Crk-associated substrate (CAS; an adapter protein associated with
      smooth muscle force development) from cytoskeletal vimentin. Expression of mutant
      S56A vimentin in cells inhibited the increase in phosphorylation at Ser-56 and in
      the ratios of soluble to insoluble vimentin (an index of vimentin disassembly)
      and the dissociation of CAS from cytoskeletal vimentin in response to 5-HT
      activation compared with cells expressing wild-type vimentin. Because CAS may be
      involved in PAK activation, PAK phosphorylation was evaluated in cells expressing
      the S56A mutant. Expression of mutant S56A vimentin depressed PAK phosphorylation
      at Thr-423 induced by 5-HT. Expression of the S56A mutant also inhibited the
      spatial reorientation of vimentin filaments in cells in response to 5-HT
      stimulation. Our results suggest that vimentin phosphorylation at Ser-56 may
      inversely regulate PAK activation possibly via the increase in the amount of
      soluble CAS upon agonist stimulation of smooth muscle cells. Additionally,
      vimentin phosphorylation at this position is critical for vimentin filament
      spatial rearrangement elicited by agonists.

PMID- 16990258
TI  - The IL sequence in the LLKIL motif in CXCR2 is required for full ligand-induced
      activation of Erk, Akt, and chemotaxis in HL60 cells.
AB  - The chemotaxis of differentiated HL60 cells stably expressing CXCR2 was examined
      in a microfluidic gradient device where the steepness of the CXCL8 chemokine
      gradient was varied from 2 pg/ml/mum (0-1 ng/ml over a width of 500 microm) to 50
      pg/ml/microm (0-25 ng/ml over 500 microm). The differentiated HL60 cells stably
      expressing CXCR2 exhibited little chemotaxis in response to a 0-1 ng/ml gradient,
      but displayed an increasing chemotactic response as the gradient steepness
      increased from 0 to 5, 0 to 10, and 0 to 25 ng/ml, demonstrating that steepness
      of gradient is a major determinant of the relative ability of cells to
      persistently migrate up a chemotactic gradient. When HL60 cells expressed CXCR2
      mutated in the C terminus LLKIL motif (IL to AA), ligand-induced internalization
      of receptors was reduced 50%, whereas cell migration along the gradient of CXCL8
      was completely lost. Although both mutant and wild-type receptors could mediate
      Akt and Erk activation in response to CXCL8, the level of activation of these two
      kinases was much lower in the cell line expressing the mutant receptors. These
      data imply that the IL amino acid residues in the LLKIL motif are very important
      for activation of the signal transduction cascade, which is necessary for cells
      to sense the chemokine gradient and respond with chemotaxis. Moreover, because
      mutation of the IL residues in the LLKIL motif resulted in only 50% reduction in
      receptor internalization, and a 50% reduction in Akt and Erk phosphorylation, but
      a complete loss of chemotactic response, the data imply that IL amino acid
      residues in the LLKIL motif are key either for amplification or oscillation of
      crucial signaling events or for establishment of a threshold for signals required
      for chemotaxis.

PMID- 16990260
TI  - The human renin kidney enhancer is required to maintain base-line renin
      expression but is dispensable for tissue-specific, cell-specific, and regulated
      expression.
AB  - Renin is the rate-limiting enzyme in the renin-angiotensin system and thus
      dictates the level of the pressor hormone angiotensin-II. The classical site of
      renin expression and secretion is the renal juxtaglomerular cell, where its
      expression is tightly regulated by physiological cues. An evolutionarily
      conserved transcriptional enhancer located 11 kb upstream of the human RENIN gene
      has been reported to markedly enhance transcription in renin expressing cells in
      vitro. However, its importance in vivo remains unclear. We tested whether this
      enhancer is required for appropriate tissue- and cell-specific expression, or for
      physiological regulation of the human RENIN gene. To accomplish this, we used a
      retrofitting technique employing homologous recombination in bacteria to delete
      the enhancer from a 160-kb P1-artificial chromosome containing human RENIN, two
      upstream genes and one downstream gene, and then generated two lines of
      transgenic mice. We previously showed that human renin expression in transgenic
      mice containing the wild type construct is tightly regulated as is expression of
      the linked genes. Deletion of the enhancer had no effect on tissue-specific
      expression of human RENIN, but using the downstream gene as an internal control,
      found that human RENIN mRNA levels were 3-10-fold decreased compared with
      constructs containing the enhancer. Despite this decrease in expression, renin
      protein remained localized to renal juxtaglomerular cells and was appropriately
      regulated by cues that either increase or decrease expression of renin. Our
      results suggest that sequences other than the enhancer may be necessary for
      tissue-specific, cell-specific, and regulated expression of human RENIN.

PMID- 16990259
TI  - X-ray crystal structures of the estrogen-related receptor-gamma ligand binding
      domain in three functional states reveal the molecular basis of small molecule
      regulation.
AB  - X-ray crystal structures of the ligand binding domain (LBD) of the estrogen
      related receptor-gamma (ERRgamma) were determined that describe this receptor in
      three distinct states: unliganded, inverse agonist bound, and agonist bound. Two
      structures were solved for the unliganded state, the ERRgamma LBD alone, and in
      complex with a coregulator peptide representing a portion of receptor interacting
      protein 140 (RIP140). No significant differences were seen between these
      structures that both exhibited the conformation of ERRgamma seen in studies with
      other coactivators. Two structures were obtained describing the inverse agonist
      bound state, the ERRgamma LBD with 4-hydroxytamoxifen (4-OHT), and the ERRgamma
      LBD with 4-OHT and a peptide representing a portion of the silencing mediator of
      retinoid and thyroid hormone action protein (SMRT). The 4-OHT structure was
      similar to other reported inverse agonist bound structures, showing reorientation
      of phenylalanine 435 and a displacement of the AF-2 helix relative to the
      unliganded structures with little other rearrangement occurring. No significant
      changes to the LBD appear to be induced by peptide binding with the addition of
      the SMRT peptide to the ERRgamma plus 4-OHT complex. The observed agonist-bound
      state contains the ERRgamma LBD, a ligand (GSK4716), and the RIP140 peptide and
      reveals an unexpected rearrangement of the phenol-binding residues. Thermal
      stability studies show that agonist binding leads to global stabilization of the
      ligand binding domain. In contrast to the conventional mechanism of nuclear
      receptor ligand activation, activation of ERRgamma by GSK4716 does not appear to
      involve a major rearrangement or significant stabilization of the C-terminal
      helix.

PMID- 16990261
TI  - A catalytic mechanism revealed by the crystal structures of the
      imidazolonepropionase from Bacillus subtilis.
AB  - Imidazolonepropionase (EC 3.5.2.7) catalyzes the third step in the universal
      histidine degradation pathway, hydrolyzing the carbon-nitrogen bonds in 4
      imidazolone-5-propionic acid to yield N-formimino-l-glutamic acid. Here we report
      the crystal structures of the Bacillus subtilis imidazolonepropionase and its
      complex at 2.0-A resolution with substrate analog imidazole-4-acetic acid sodium
      (I4AA). The structure of the native enzyme contains two domains, a TIM (triose
      phosphate isomerase) barrel domain with two insertions and a small beta-sandwich
      domain. The TIM barrel domain is quite similar to the members of the alpha/beta
      barrel metallo-dependent hydrolase superfamily, especially to Escherichia coli
      cytosine deaminase. A metal ion was found in the central cavity of the TIM barrel
      and was tightly coordinated to residues His-80, His-82, His-249, Asp-324, and a
      water molecule. X-ray fluorescence scan analysis confirmed that the bound metal
      ion was a zinc ion. An acetate ion, 6 A away from the zinc ion, was also found in
      the potential active site. In the complex structure with I4AA, a substrate
      analog, I4AA replaced the acetate ion and contacted with Arg-89, Try-102, Tyr
      152, His-185, and Glu-252, further defining and confirming the active site. The
      detailed structural studies allowed us to propose a zinc-activated nucleophilic
      attack mechanism for the hydrolysis reaction catalyzed by the enzyme.

PMID- 16990262
TI  - Charged extracellular residues, conserved throughout a G-protein-coupled receptor
      family, are required for ligand binding, receptor activation, and cell-surface
      expression.
AB  - For G-protein-coupled receptors (GPCRs) in general, the roles of extracellular
      residues are not well defined compared with residues in transmembrane helices
      (TMs). Nevertheless, extracellular residues are important for various functions
      in both peptide-GPCRs and amine-GPCRs. In this study, the V(1a) vasopressin
      receptor was used to systematically investigate the role of extracellular charged
      residues that are highly conserved throughout a subfamily of peptide-GPCRs, using
      a combination of mutagenesis and molecular modeling. Of the 13 conserved charged
      residues identified in the extracellular loops (ECLs), Arg(116) (ECL1), Arg(125)
      (top of TMIII), and Asp(204) (ECL2) are important for agonist binding and/or
      receptor activation. Molecular modeling revealed that Arg(125) (and Lys(125))
      stabilizes TMIII by interacting with lipid head groups. Charge reversal
      (Asp(125)) caused re-ordering of the lipids, altered helical packing, and
      increased solvent penetration of the TM bundle. Interestingly, a negative charge
      is excluded at this locus in peptide-GPCRs, whereas a positive charge is excluded
      in amine-GPCRs. This contrasting conserved charge may reflect differences in GPCR
      binding modes between peptides and amines, with amines needing to access a
      binding site crevice within the receptor TM bundle, whereas the binding site of
      peptide-GPCRs includes more extracellular domains. A conserved negative charge at
      residue 204 (ECL2), juxtaposed to the highly conserved disulfide bond, was
      essential for agonist binding and signaling. Asp(204) (and Glu(204)) establishes
      TMIII contacts required for maintaining the beta-hairpin fold of ECL2, which if
      broken (Ala(204) or Arg(204)) resulted in ECL2 unfolding and receptor
      dysfunction. This study provides mechanistic insight into the roles of conserved
      extracellular residues.

PMID- 16990263
TI  - Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase.
AB  - Mosquitoes are unique in having evolved two alanine glyoxylate aminotransferases
      (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily
      responsible for catalyzing the transamination of 3-hydroxykynurenine (3-HK) to
      xanthurenic acid (XA). Interestingly, XA is used by malaria parasites as a
      chemical trigger for their development within the mosquito. This 3-HK to XA
      conversion is considered the major mechanism mosquitoes use to detoxify the
      chemically reactive and potentially toxic 3-HK. The other AGT is a typical
      dipteran insect AGT and is specific for converting glyoxylic acid to glycine.
      Here we report the 1.75A high-resolution three-dimensional crystal structure of
      AGT from the mosquito Aedes aegypti (AeAGT) and structures of its complexes with
      reactants glyoxylic acid and alanine at 1.75 and 2.1A resolution, respectively.
      This is the first time that the three-dimensional crystal structures of an AGT
      with its amino acceptor, glyoxylic acid, and amino donor, alanine, have been
      determined. The protein is dimeric and adopts the type I-fold of pyridoxal 5
      phosphate (PLP)-dependent aminotransferases. The PLP co-factor is covalently
      bound to the active site in the crystal structure, and its binding site is
      similar to those of other AGTs. The comparison of the AeAGT-glyoxylic acid
      structure with other AGT structures revealed that these glyoxylic acid binding
      residues are conserved in most AGTs. Comparison of the AeAGT-alanine structure
      with that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe
      motif in the latter may be responsible for the substrate specificity of HKT
      enzymes for 3-HK.

PMID- 16990264
TI  - Crystal structure of the galectin-9 N-terminal carbohydrate recognition domain
      from Mus musculus reveals the basic mechanism of carbohydrate recognition.
AB  - The galectins are a family of beta-galactoside-binding animal lectins with a
      conserved carbohydrate recognition domain (CRD). They have a high affinity for
      small beta-galactosides, but binding specificity for complex glycoconjugates
      varies considerably within the family. The ligand recognition is essential for
      their proper function, and the structures of several galectins have suggested
      their mechanism of carbohydrate binding. Galectin-9 has two tandem CRDs with a
      short linker, and we report the crystal structures of mouse galectin-9 N-terminal
      CRD (NCRD) in the absence and the presence of four ligand complexes. All
      structures form the same dimer, which is quite different from the canonical 2
      fold symmetric dimer seen for galectin-1 and -2. The beta-galactoside recognition
      mechanism in the galectin-9 NCRD is highly conserved among other galectins. In
      the apo form structure, water molecules mimic the ligand hydrogen-bond network.
      The galectin-9 NCRD can bind both N-acetyllactosamine (Galbeta1-4GlcNAc) and T
      antigen (Galbeta1-3GalNAc) with the proper location of Arg-64. Moreover, the
      structure of the N-acetyllactosamine dimer (Galbeta1-4GlcNAcbeta1-3Galbeta1
      4GlcNAc) complex shows a unique binding mode of galectin-9. Finally, surface
      plasmon resonance assay showed that the galectin-9 NCRD forms a homophilic dimer
      not only in the crystal but also in solution.

PMID- 16990265
TI  - Structural rearrangements of sucrose phosphorylase from Bifidobacterium
      adolescentis during sucrose conversion.
AB  - The reaction mechanism of sucrose phosphorylase from Bifidobacterium adolescentis
      (BiSP) was studied by site-directed mutagenesis and x-ray crystallography. An
      inactive mutant of BiSP (E232Q) was co-crystallized with sucrose. The structure
      revealed a substrate-binding mode comparable with that seen in other related
      sucrose-acting enzymes. Wild-type BiSP was also crystallized in the presence of
      sucrose. In the dimeric structure, a covalent glucosyl intermediate was formed in
      one molecule of the BiSP dimer, and after hydrolysis of the glucosyl
      intermediate, a beta-D-glucose product complex was formed in the other molecule.
      Although the overall structure of the BiSP-glucosyl intermediate complex is
      similar to that of the BiSP(E232Q)-sucrose complex, the glucose complex discloses
      major differences in loop conformations. Two loops (residues 336-344 and 132-137)
      in the proximity of the active site move up to 16 and 4 A, respectively. On the
      basis of these findings, we have suggested a reaction cycle that takes into
      account the large movements in the active-site entrance loops.

PMID- 16990266
TI  - AMP-activated protein kinase and the regulation of autophagic proteolysis.
AB  - Interruption of mTOR-dependent signaling by rapamycin is known to stimulate
      autophagy, both in mammalian cells and in yeast. Because activation of AMPK also
      inhibits mTOR-dependent signaling one would expect stimulation of autophagy by
      AMPK activation. According to the literature, this is true for yeast but,
      unexpectedly, not for mammalian cells on the basis of the use of AICAR, a
      pharmacological activator of AMPK. In the present study, carried out with
      hepatocytes, HT-29 cells, and HeLa cells, we have reexamined the possible role of
      AMPK in the control of mammalian autophagy. Inhibition of AMPK activity by
      compound C or by transfection with a dominant negative form of AMPK almost
      completely inhibited autophagy. These results suggest that the inhibition of
      autophagy by AICAR is not related to its ability to activate AMPK. We conclude
      that in mammalian cells, as in yeast, AMPK is required for autophagy.

PMID- 16990267
TI  - First structure of a eukaryotic phosphohistidine phosphatase.
AB  - Phosphatases are a diverse group of enzymes that regulate numerous cellular
      processes. Much of what is known relates to the tyrosine, threonine, and serine
      phosphatases, whereas the histidine phosphatases have not been studied as much.
      The structure of phosphohistidine phosphatase (PHPT1), the first identified
      eukaryotic-protein histidine phosphatase, has been determined to a resolution of
      1.9A using multiple-wavelength anomalous dispersion methods. This enzyme can
      dephosphorylate a variety of proteins (e.g. ATP-citrate lyase and the beta
      subunit of G proteins). A putative active site has been identified by its
      electrostatic character, ion binding, and conserved protein residues. Histidine
      53 is proposed to play a major role in histidine dephosphorylation based on these
      observations and previous mutational studies. Models of peptide binding are
      discussed to suggest possible mechanisms for substrate recognition.

PMID- 16990268
TI  - DANGER, a novel regulatory protein of inositol 1,4,5-trisphosphate-receptor
      activity.
AB  - We report the cloning and characterization of DANGER, a novel protein which
      physiologically binds to inositol 1,4,5-trisphosphate receptors (IP(3)R). DANGER
      is a membrane-associated protein predicted to contain a partial MAB-21 domain. It
      is expressed in a wide variety of neuronal cell lineages where it localizes to
      membranes in the cell periphery together with IP(3)R. DANGER interacts with
      IP(3)R in vitro and co-immunoprecipitates with IP(3)R from cellular preparations.
      DANGER robustly enhances Ca(2+)-mediated inhibition of IP(3) RCa(2+) release
      without affecting IP(3) binding in microsomal assays and inhibits gating in
      single-channel recordings of IP(3)R. DANGER appears to allosterically modulate
      the sensitivity of IP(3) RtoCa(2+) inhibition, which likely alters IP(3)R
      mediated Ca(2+) dynamics in cells where DANGER and IP(3)R are co-expressed.

PMID- 16990269
TI  - Involvement of helix 34 of 16 S rRNA in decoding and translocation on the
      ribosome.
AB  - Helix 34 of 16 S rRNA is located in the head of the 30 S ribosomal subunit close
      to the decoding center and has been invoked in a number of ribosome functions. In
      the present work, we have studied the effects of mutations in helix 34 both in
      vivo and in vitro. Several nucleotides in helix 34 that are either highly
      conserved or form important tertiary contacts in 16 S rRNA (U961, C1109, A1191,
      and A1201) were mutated, and the mutant ribosomes were expressed in the
      Escherichia coli MC250 Delta7 strain that lacks all seven chromosomal rRNA
      operons. Mutations at positions A1191 and U961 reduced the efficiency of subunit
      association and resulted in structural rearrangements in helix 27 (position 908)
      and helix 31 (position 974) of 16 S rRNA. All mutants exhibited increased levels
      of frameshifting and nonsense readthrough. The effects on frameshifting were
      specific in that -1 frameshifting was enhanced with mutant A1191G and +1
      frameshifting with the other mutants. Mutations of A1191 moderately
      (approximately 2-fold) inhibited tRNA translocation. No significant effects were
      found on efficiency and rate of initiation, misreading of sense codons, or
      binding of tRNA to the E site. The data indicate that helix 34 is involved in
      controlling the maintenance of the reading frame and in tRNA translocation.

PMID- 16990270
TI  - Hormone-response genes are direct in vivo regulatory targets of Brahma (SWI/SNF)
      complex function.
AB  - Metazoan SWI/SNF chromatin remodeling complexes exhibit ATP-dependent activation
      and repression of target genes. The Drosophila Brahma (SWI/SNF) complex subunits
      BRM and SNR1 are highly conserved with direct counterparts in yeast (SWI2/SNF2
      and SNF5) and mammals (BRG1/hBRM and INI1/hSNF5). BRM encodes the catalytic
      ATPase required for chromatin remodeling and SNR1 is a regulatory subunit.
      Importantly, SNR1 mediates ATP-independent repression functions of the complex in
      cooperation with histone deacetylases and direct contacts with gene-specific
      repressors. SNR1 and INI1, as components of their respective SWI/SNF complexes,
      are important for developmental growth control and patterning, with direct
      function as a tumor suppressor. To identify direct regulatory targets of the Brm
      complex, we performed oligonucleotide-based transcriptome microarray analyses
      using RNA isolated from mutant fly strains harboring dominant-negative alleles of
      snr1 and brm. Steady-state RNA isolated from early pupae was examined, as this
      developmental stage critically requires Brm complex function. We found the
      hormone-responsive Ecdysone-induced genes (Eig) were strongly misregulated and
      that the Brm complex is directly associated with the promoter regions of these
      genes in vivo. Our results reveal that the Brm complex assists in coordinating
      hormone-dependent transcription regulation of the Eig genes.

PMID- 16990272
TI  - Evaluation of the roles of apoptosis, autophagy, and mitophagy in the loss of
      plating efficiency induced by Bax expression in yeast.
AB  - We found recently that, in yeast cells, the heterologous expression of Bax
      induces a loss of plating efficiency different from that induced by acute stress
      because it is associated with the maintenance of plasma membrane integrity
      (Camougrand, N., Grelaud-Coq, A., Marza, E., Priault, M., Bessoule, J. J., and
      Manon, S. (2003) Mol. Microbiol. 47, 495-506). Bax effects were neither dependent
      on the presence of the yeast metacaspase Yca1p and the apoptosis-inducing factor
      homolog nor associated with the appearance of typical apoptotic markers such as
      metacaspase activation, annexin V binding, and DNA cleavage. Yeast cells
      expressing Bax instead displayed autophagic features, including increased
      accumulation of Atg8p, activation of vacuolar alkaline phosphatase, and the
      presence of autophagosomes and autophagic bodies. However, the inactivation of
      autophagy did not prevent and actually slightly accelerated Bax-induced loss of
      plating efficiency. On the other hand, Bax expression induced a fragmentation of
      the mitochondrial network, which retained, however, some level of organization in
      wild-type cells. However, when expressed in cells inactivated for the gene UTH1,
      previously shown to be involved in mitophagy, Bax induced a complete
      disorganization of the mitochondrial network. Interestingly, although
      mitochondrially targeted green fluorescent protein was slowly degraded in the
      wild-type strain, it remained unaffected in the mutant. Furthermore, the slow
      loss of plating efficiency in the mutant strain correlated with a loss of plasma
      membrane integrity. These data suggest that Bax-induced loss of growth capacity
      is associated with maintenance of plasma membrane integrity dependent on UTH1,
      suggesting that selective degradation of altered mitochondria is required for a
      regulated loss of growth capacity.

PMID- 16990271
TI  - Cytoplasmic targeting motifs control localization of toll-like receptor 9.
AB  - Toll-like receptors (TLRs) are essential for host defense. Although several TLRs
      reside on the cell surface, nucleic acid recognition of TLRs occurs
      intracellularly. For example, the receptor for CpG containing bacterial and viral
      DNA, TLR9, is retained in the endoplasmic reticulum. Recent evidence suggests
      that the localization of TLR9 is critical for appropriate ligand recognition.
      Here we have defined which structural features of the TLR9 molecule control its
      intracellular localization. Both the cytoplasmic and ectodomains of TLR9 contain
      sufficient information, whereas the transmembrane domain plays no role in
      intracellular localization. We identify a 14-amino acid stretch that directs TLR9
      intracellularly and confers intracellular localization to the normally cell
      surface-expressed TLR4. Truncation or mutation of the cytoplasmic tail of TLR9
      reveals a vesicle localization motif that targets early endosomes. We propose a
      model whereby modification of the cytoplasmic tail of TLR9 results in trafficking
      to early endosomes where it encounters CpG DNA.

PMID- 16990273
TI  - Helicobacter pylori induces gastric epithelial cell invasion in a c-Met and type
      IV secretion system-dependent manner.
AB  - Helicobacter pylori interacts with gastric epithelial cells, activating signaling
      pathways important for carcinogenesis. In this study we examined the role of H.
      pylori on cell invasion and the molecular mechanisms underlying this process. The
      relevance of H. pylori cag pathogenicity island-encoded type IV secretion system
      (T4SS), CagA, and VacA for cell invasion was also investigated. We found that H.
      pylori induces AGS cell invasion in collagen type I and in Matrigel invasion
      assays. H. pylori-induced cell invasion requires the direct contact between
      bacteria and cancer cells. H. pylori-mediated cell invasion was dependent on the
      activation of the c-Met receptor and on increased MMP-2 and MMP-9 activity. The
      abrogation of the c-Met receptor using the specific NK4 inhibitor or the
      silencing of c-Met expression with small interference RNA suppressed both cell
      invasion and MMP activity. Studies with different H. pylori strains revealed that
      cell invasion, c-Met tyrosine phosphorylation, and increased MMP-2 and MMP-9
      activity were all dependent on the presence of a functional bacterial T4SS, but
      not on VacA cytotoxicity. Our findings demonstrate that H. pylori strains with a
      functional T4SS stimulate gastric epithelial cell invasion through a c-Met
      dependent signaling pathway that comprises an increase in MMP-2 and MMP-9
      activity.

PMID- 16990274
TI  - Combination of NADPH and copper ions generates proteinase K-resistant aggregates
      from recombinant prion protein.
AB  - Recent studies have demonstrated that the octapeptide repeats of the N-terminal
      region of prion protein may be responsible for de novo generation of infectious
      prions in the absence of template. Here we demonstrate that PrP-(23-98), an N
      terminal portion of PrP, is converted to aggregates upon incubation with NADPH
      and copper ions. Other pyridine nucleotides possessing a phosphate group on the
      adenine-linked ribose moiety (the reduced form of nicotinamide adenine
      dinucleotide 3'-phosphate, nicotinic acid adenine dinucleotide phosphate, and
      NADP) were also effective in promoting aggregation, but NADH and NAD had no
      effect. The aggregation was attenuated by the metal chelator EDTA or by
      modification of histidyl residues with diethyl pyrocarbonate. The aggregates are
      amyloid-like as judged by the binding of thioflavin T, a fluorescent probe for
      amyloid, but do not exhibit fibrillar structures according to electron
      micrography. Interestingly the aggregates were resistant to proteinase K
      digestion. Likewise NADPH and zinc ions caused aggregation of PrP-(23-98), but
      the resulting aggregates were susceptible to degradation by proteinase K. Upon
      incubation with NADPH and copper ions, the full-length molecule PrP-(23-231) also
      formed proteinase K-resistant amyloid-like aggregates. Because it is possible
      that PrP, NADPH, and copper ions could associate in certain tissues, the
      aggregation observed in this study may be involved in prion initiation especially
      in the nonfamilial types of prion diseases.

PMID- 16990275
TI  - Cysteine accessibility in the hydrophilic cleft of human organic cation
      transporter 2.
AB  - Organic cation transporters (OCTs) are involved in the renal elimination of many
      cationic drugs and toxins. A hypothetical three-dimensional structure of OCT2
      based on a homology model that used the Escherichia coli glycerol 3-phosphate
      transporter as a template has been described (Zhang, X., Shirahatti, N. V.,
      Mahadevan, D., and Wright, S. H. (2005) J. Biol. Chem. 280, 34813-34822). To
      further define OCT structure, the accessibility to hydrophilic thiol-reactive
      reagents of the 13 cysteine residues contained in the human ortholog of OCT2 was
      examined. Maleimide-PEO2-biotin precipitated (surface biotinylation followed by
      Western blotting) and reduced tetraethylammonium transport by OCT2 expressed in
      Chinese hamster ovary cells, effects that were largely reversed by co-exposure to
      substrates and transport inhibitors, suggesting interaction with cysteines that
      are near to or part of a substrate-binding surface. Cysteines at amino acid
      position 437, 451, 470, and 474 were identified from the model as being located
      in transmembrane helices that participate in forming the hydrophilic cleft, the
      proposed region of substrate-protein interaction. To determine which residues are
      exposed to the solvent, a mutant with all four of these cysteines converted to
      alanine, along with four variants of this mutant each with an individual cysteine
      restored, were created. Maleimide-PEO2-biotin was only effective at precipitating
      and reducing transport by wild-type OCT2 and the mutant with cysteine 474
      restored. Additionally, the smaller thiol-reactive reagent, methanethiosulfonate
      ethylsulfonate, reduced transport by wild-type OCT2 and the mutant with cysteine
      474 restored. These data demonstrate that cysteine 474 of OCT2 is exposed to the
      aqueous milieu of the cleft and contributes to forming a pathway for organic
      cation transport.

PMID- 16990276
TI  - Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit
      composition and cAMP-response element-binding protein regulate oligodendrocyte
      excitotoxicity.
AB  - Developing oligodendrocytes (OLs) are highly vulnerable to glutamate
      excitotoxicity. Although OL excitotoxicity is mainly mediated by alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors (AMPARs) and is Ca2+
      dependent, the molecular basis for AMPAR-mediated Ca2+ influx in OLs remains
      largely unclear. Ca2+ permeability of AMPARs is inversely correlated with the
      abundance of the AMPAR subunit glutamate receptor 2 (GluR2). Here we report that
      GluR2-containing and GluR2-lacking AMPARs are co-expressed in individual OLs and
      that a subset of AMPARs on each OL are Ca2+-permeable and mediate OL
      excitotoxicity. Virus-mediated overexpression of GluR2 reduces OL excitotoxicity,
      whereas expression of its unedited form GluR2(Q) enhances the excitotoxicity.
      These findings indicate that GluR2 critically controls OL excitotoxicity. During
      OL excitotoxicity, the transcriptional factor cAMP-response element-binding
      protein (CREB) is transiently phosphorylated and subsequently down-regulated.
      Virus-mediated expression of a constitutively active form of CREB, both in
      cultured OLs in vitro and in developing cerebral white matter in vivo, up
      regulates GluR2, inhibits Ca2+ permeability, and protects OLs from
      excitotoxicity. Overall, these data suggest that targeting GluR2-lacking AMPARs
      or CREB may be a useful strategy for treating nervous system disorders associated
      with OL excitotoxicity.

PMID- 16990277
TI  - Fission yeast homologs of human histone H3 lysine 4 demethylase regulate a common
      set of genes with diverse functions.
AB  - Schizosaccharomyces pombe contains two proteins, SWIRM1 and SWIRM2, with close
      homology to human histone H3 lysine 4 demethylase. Both proteins contain the
      amino oxidase catalytic domain and a recently described DNA interaction SWIRM
      domain. Here we describe the biochemical isolation and the functional
      characterization of SWIRM1 and SWIRM2. Our results indicate that while SWIRM2 is
      an essential gene, cells lacking SWIRM1 are viable. We found that SWIRM1 and
      SWIRM2 are stably associated in a multiprotein complex, but intriguingly, unlike
      their human counterpart, S. pombe SWIRM complex contains neither a histone
      deacetylase nor any detectable demethylase activity. Genome-wide chromatin
      immunoprecipitation unexpectedly showed the absence of both SWIRM proteins from
      heterochromatic domains. Instead, consistent with biochemical analyses, SWIRM1
      and SWIRM2 co-localize to a common set of target gene promoters whose functions
      are implicated in diverse processes including mitochondrial metabolism and
      transcriptional regulation. Importantly, we show that SWIRM1 is not only required
      for optimum transcription of its target genes but also display a global role in
      regulation of antisense transcription.

PMID- 16990278
TI  - The interaction of a carbohydrate-binding module from a Clostridium perfringens N
      acetyl-beta-hexosaminidase with its carbohydrate receptor.
AB  - Clostridium perfringens is a notable colonizer of the human gastrointestinal
      tract. This bacterium is quite remarkable for a human pathogen by the number of
      glycoside hydrolases found in its genome. The modularity of these enzymes is
      striking as is the frequent occurrence of modules having amino acid sequence
      identity with family 32 carbohydrate-binding modules (CBMs), often referred to as
      F5/8 domains. Here we report the properties of family 32 CBMs from a C.
      perfringens N-acetyl-beta-hexosaminidase. Macroarray, UV difference, and
      isothermal titration calorimetry binding studies indicate a preference for the
      disaccharide LacNAc (beta-d-galactosyl-1,4-beta-d-N-acetylglucosamine). The
      molecular details of the interaction of this CBM with galactose, LacNAc, and the
      type II blood group H-trisaccharide are revealed by x-ray crystallographic
      studies at resolutions of 1.49, 2.4, and 2.3 A, respectively.

PMID- 16990279
TI  - Genome-wide analysis of substrate specificities of the Escherichia coli haloacid
      dehalogenase-like phosphatase family.
AB  - Haloacid dehalogenase (HAD)-like hydrolases are a vast superfamily of largely
      uncharacterized enzymes, with a few members shown to possess phosphatase, beta
      phosphoglucomutase, phosphonatase, and dehalogenase activities. Using a
      representative set of 80 phosphorylated substrates, we characterized the
      substrate specificities of 23 soluble HADs encoded in the Escherichia coli
      genome. We identified small molecule phosphatase activity in 21 HADs and beta
      phosphoglucomutase activity in one protein. The E. coli HAD phosphatases show
      high catalytic efficiency and affinity to a wide range of phosphorylated
      metabolites that are intermediates of various metabolic reactions. Rather than
      following the classical "one enzyme-one substrate" model, most of the E. coli
      HADs show remarkably broad and overlapping substrate spectra. At least 12
      reactions catalyzed by HADs currently have no EC numbers assigned in Enzyme
      Nomenclature. Surprisingly, most HADs hydrolyzed small phosphodonors (acetyl
      phosphate, carbamoyl phosphate, and phosphoramidate), which also serve as
      substrates for autophosphorylation of the receiver domains of the two-component
      signal transduction systems. The physiological relevance of the phosphatase
      activity with the preferred substrate was validated in vivo for one of the HADs,
      YniC. Many of the secondary activities of HADs might have no immediate
      physiological function but could comprise a reservoir for evolution of novel
      phosphatases.

PMID- 16990280
TI  - Nephrocan, a novel member of the small leucine-rich repeat protein family, is an
      inhibitor of transforming growth factor-beta signaling.
AB  - In a search of new, small leucine-rich repeat proteoglycan/protein (SLRP) family
      members, a novel gene, nephrocan (NPN), has been identified. The gene consists of
      three exons, and based on the deduced amino acid sequence, NPN has 17 leucine
      rich repeat motifs and unique cysteine-rich clusters both in the N and C termini,
      indicating that this gene belongs to a new class of SLRP family. NPN mRNA was
      predominantly expressed in kidney in adult mice, and during mouse embryogenesis,
      the expression was markedly increased in 11-day-old embryos at a time when early
      kidney development takes place. In the adult mouse kidney, NPN protein was
      located in distal tubules and collecting ducts. When NPN was overexpressed in
      cell culture, the protein was detected in the cultured medium, and upon treatment
      with N-glycosidase F, the molecular mass was lowered by approximately 14 kDa,
      indicating that NPN is a secreted N-glycosylated protein. Furthermore,
      transforming growth factor-beta (TGF-beta)-responsive 3TP promoter luciferase
      activity was down-regulated, and TGF-beta-induced Smad3 phosphorylation was also
      inhibited by NPN, suggesting that NPN suppresses TGF-beta/Smad signaling. Taken
      together, NPN is a novel member of the SLRP family that may play important roles
      in kidney development and pathophysiology by functioning as an endogenous
      inhibitor of TGF-beta signaling.

PMID- 16990281
TI  - Biochemical and NMR study on the competition between proteins SC35, SRp40, and
      heterogeneous nuclear ribonucleoprotein A1 at the HIV-1 Tat exon 2 splicing site.
AB  - The human immunodeficiency virus, type 1, Tat protein plays a key role in virus
      multiplication. Because of its apoptotic property, its production is highly
      controlled. It depends upon the A3 splicing site utilization. A key control of
      site A3 activity is the ESS2 splicing silencer, which is located within the long
      stem-loop structure 3 (SLS3), far downstream from site A3. Here, by enzymatic
      footprints, we demonstrate the presence of several heterogeneous nuclear
      ribonucleoprotein (hnRNP) A1-binding sites on SLS3 and show the importance of the
      C-terminal Gly domain of hnRNP A1 in the formation of stable complexes containing
      several hnRNP A1 molecules bound on SLS3. Mutations in each of the UAG triplets
      in ESS2 strongly reduce the overall hnRNP A1 binding, showing the central role of
      ESS2 in hnRNP A1 assembly on SLS2-SLS3. Using NMR spectroscopy, we demonstrate
      the direct interaction of ESS2 with the RNA recognition motifs domains of hnRNP
      A1. This interaction has limited effect on the RNA two-dimensional structure. The
      SR proteins SC35 and SRp40 were found previously to be strong activators of site
      A3 utilization. By enzymatic and chemical footprints, we delineate their
      respective binding sites on SLS2 and SLS3 and find a strong similarity between
      the hnRNP A1-, SC35-, and SRp40-binding sites. The strongest SC35-binding site
      only has a modest contribution to site A3 activation. Hence, the main role of SR
      proteins at site A3 is to counteract hnRNP A1 binding on ESS2 and ESE2. Indeed,
      we found that ESE2 has inhibitory properties because of its ability to bind hnRNP
      A1.

PMID- 16990282
TI  - The potassium channel KAT1 is activated by plant and animal 14-3-3 proteins.
AB  - 14-3-3 proteins modulate the plant inward rectifier K+ channel KAT1
      heterologously expressed in Xenopus oocytes. Injection of recombinant plant 14-3
      3 proteins into oocytes shifted the activation curve of KAT1 by +11 mV and
      increased the tau(on). KAT1 was also modulated by 14-3-3 proteins of Xenopus
      oocytes. Titration of the endogenous 14-3-3 proteins by injection of the peptide
      Raf 621p resulted in a strong decrease in KAT1 current (approximately 70% at -150
      mV). The mutation K56E performed on plant protein 14-3-3 in a highly conserved
      recognition site prevented channel activation. Because the maximal conductance of
      KAT1 was unaffected by 14-3-3, we can exclude that they act by increasing the
      number of channels, thus ruling out any effect of these proteins on channel
      trafficking and/or insertion into the oocyte membrane. 14-3-3 proteins also
      increased KAT1 current in inside-out patches, suggesting a direct interaction
      with the channel. Direct interaction was confirmed by overlay experiments with
      radioactive 14-3-3 on oocyte membranes expressing KAT1.

PMID- 16990283
TI  - Voltage gating of VDAC is regulated by nonlamellar lipids of mitochondrial
      membranes.
AB  - Evidence is accumulating that lipids play important roles in permeabilization of
      the mitochondria outer membrane (MOM) at the early stage of apoptosis. Lamellar
      phosphatidylcholine (PC) and nonlamellar phosphatidylethanolamine (PE) lipids are
      the major membrane components of the MOM. Cardiolipin (CL), the characteristic
      lipid from the mitochondrial inner membrane, is another nonlamellar lipid
      recently shown to play a role in MOM permeabilization. We investigate the effect
      of these three key lipids on the gating properties of the voltage-dependent anion
      channel (VDAC), the major channel in MOM. We find that PE induces voltage
      asymmetry in VDAC current-voltage characteristics by promoting channel closure at
      cis negative applied potentials. Significant asymmetry is also induced by CL. The
      observed differences in VDAC behavior in PC and PE membranes cannot be explained
      by differences in the insertion orientation of VDAC in these membranes. Rather,
      it is clear that the two nonlamellar lipids affect VDAC gating. Using gramicidin
      A channels as a tool to probe bilayer mechanics, we show that VDAC channels are
      much more sensitive to the presence of CL than could be expected from the
      experiments with gramicidin channels. We suggest that this is due to the
      preferential insertion of VDAC into CL-rich domains. We propose that the specific
      lipid composition of the mitochondria outer membrane and/or of contact sites
      might influence MOM permeability by regulating VDAC gating.

PMID- 16990284
TI  - Commentary: cancer--evolution within.

PMID- 16990285
TI  - Commentary: carcinogenesis as Darwinian evolution? Do the math!

PMID- 16990286
TI  - Commentary: evolution of action in cells and organisms.

PMID- 16990287
TI  - Commentary: induction and selection of variations during cancer development.

PMID- 16990288
TI  - Magnetic resonance imaging in a patient with chronic lithium nephropathy.

PMID- 16990289
TI  - Identification of active transposon dTok, a member of the hAT family, in rice.
AB  - Recent completion of the sequencing of the rice genome has revealed that it
      contains >40% repetitive sequences, most of which are related to inactive
      transposable elements. During the molecular analysis of the floral organ number
      1/multiple pistil 2 (fon1/mp2) mutant, we identified an active transposable
      element dTok0 that was inserted at the kinase domain of FON1, a homolog of
      CLAVATA1. Insertion of the element into FON1 generated an 8 bp duplication of its
      target sites, which is one of the major characteristics of the hAT family of
      transposons. The dTok0 element was actively transposed out of the FON1 gene,
      leaving 5-8 bp footprints. Reinsertion into a new location was observed at a low
      frequency. Analysis of the genome sequence showed that the rice cultivar
      'Nipponbare' contains 25 copies of dTok elements; similar numbers were present in
      all the Oryza species examined. Because dTok0 does not encode a transposase,
      enzyme activity should be provided in trans. We identified a putative autonomous
      transposon, Tok1 that contains an intact open reading frame of the Ac-like
      transposase.

PMID- 16990290
TI  - Abscisic acid is a key inducer of hydrogen peroxide production in leaves of maize
      plants exposed to water stress.
AB  - The histochemical and cytochemical localization of water stress-induced H(2)O(2)
      production in the leaves of ABA-deficient vp5 mutant and wild-type maize (Zea
      mays L.) plants were examined, using 3,3-diaminobenzidine and CeCl(3) staining,
      respectively, and the roles of endogenous ABA in the production of H(2)O(2)
      induced by water stress were assessed. Water stress induced by polyethylene
      glycol resulted in the accumulation of H(2)O(2) in mesophyll cells, bundle-sheath
      cells and vascular bundles of wild-type maize leaves, and the accumulation was
      substantially blocked in the mutant maize leaves exposed to water stress. Pre
      treatments with several apoplastic H(2)O(2) manipulators abolished the majority
      of H(2)O(2) accumulation induced by water stress in the wild-type leaves. The
      subcellular localization of H(2)O(2) production was demonstrated in the cell
      walls, xylem vessels, chloroplasts, mitochondria and peroxisomes in the leaves of
      wild-type maize plants exposed to water stress, and the accumulation of H(2)O(2)
      induced by water stress in the cell walls and xylem vessels, but not in the
      chloroplasts, mitochondria and peroxisomes, was arrested in the leaves of the ABA
      mutant or the ABA biosynthesis inhibitor (tungstate)-pre-treated maize plants.
      Pre-treatments with the apoplastic H(2)O(2) manipulators also blocked the
      apoplastic but not the intracellular H(2)O(2) accumulation induced by water
      stress in the leaves of wild-type plants. These data indicate that under water
      stress, the apoplast is the major source of H(2)O(2) production and ABA is a key
      inducer of apoplastic H(2)O(2) production. These data also suggest that H(2)O(2)
      generated in the apoplast could not diffuse freely into subcellular compartments.

PMID- 16990291
TI  - Rice Immature Pollen 1 (RIP1) is a regulator of late pollen development.
AB  - We isolated a pollen-preferential gene, RICE IMMATURE POLLEN 1 (RIP1), from a T
      DNA insertional population of japonica rice that was trapped by a promoterless
      beta-glucuronidase (GUS) gene. Semi-quantitative reverse transcription-PCR (RT
      PCR) analyses confirmed that the RIP1 transcript was abundant at the late stages
      of pollen development. Transgenic plants carrying a T-DNA insertion in the RIP1
      gene displayed the phenotype of segregation distortion of the mutated rip1 gene.
      Moreover, rip1/rip1 homozygous progeny were not present. Reciprocal crosses
      between Rip1/rip1 heterozygous plants and the wild type showed that the rip1
      allele could not be transmitted through the male. Microscopic analysis
      demonstrated that development in the rip1 pollen was delayed, starting at the
      early vacuolated stage. Close examination of that pollen by transmission electron
      microscopy also showed delayed formation of starch granules and the intine layer.
      In addition, development of the mitochondria, Golgi apparatus, lipid bodies,
      plastids and endoplasmic reticulum was deferred in the mutant pollen. Under in
      vitro conditions, germination of this mutant pollen did not occur, whereas the
      rate for wild-type pollen was >90%. These results indicate that RIP1 is necessary
      for pollen maturation and germination. This gene encodes a protein that shares
      significant homology with a group of proteins containing five WD40 repeat
      sequences. The green fluorescent protein (GFP)-RIP1 fusion protein is localized
      to the nucleus. Therefore, RIP1 is probably a nuclear protein that may form a
      functional complex with other proteins and carry out essential cellular and
      developmental roles during the late stage of pollen formation.

PMID- 16990292
TI  - Cardiopulmonary resuscitation: capacity, discussion and documentation.
AB  - BACKGROUND: End-of-life care decisions, including treatment such as
      cardiopulmonary resuscitation (CPR), are complex issues requiring a patient to
      have the capacity for effective decision-making. AIM: To assess the prevalence
      and documentation of CPR decisions in our hospital in patients aged > 65 years.
      DESIGN: Prospective audit. METHODS: Review of patient notes and resuscitation
      forms within our acute Trust on Elderly Care and General Medicine wards,
      including the decisions made, involvement of patient and/or family members and
      whether an assessment of capacity was made. RESULTS: On the Elderly Care wards,
      37 CPR decisions were made on 104 patients, and nearly all of these were clearly
      documented. On the General Medical wards, only one decision out of 40 patients
      was made. Geriatricians incorporated patient views in one quarter of decisions;
      all but one of these patients wanted CPR. Of those patients 'not for CPR', family
      members were informed in only one third of cases, according to the documentation.
      Capacity was documented on only four occasions. DISCUSSION: Geriatricians make
      significantly more CPR decisions than general physicians do, but still involve
      patient and family views in only a minority of cases, and an assessment of
      capacity is rarely explicitly documented. We suggest a three-step approach to
      clinical decision making, to increase both the volume and the quality of CPR
      decisions, which may be improved further by the use of information leaflets for
      patients and their families.

PMID- 16990293
TI  - Heat-related and cold-related deaths in England and Wales: who is at risk?
AB  - BACKGROUND: Despite the high burden from exposure to both hot and cold weather
      each year in England and Wales, there has been relatively little investigation on
      who is most at risk, resulting in uncertainties in informing government
      interventions. OBJECTIVE: To determine the subgroups of the population that are
      most vulnerable to heat-related and cold-related mortality. METHODS: Ecological
      time-series study of daily mortality in all regions of England and Wales between
      1993 and 2003, with postcode linkage of individual deaths to a UK database of all
      care and nursing homes, and 2001 UK census small-area indicators. RESULTS: A risk
      of mortality was observed for both heat and cold exposure in all regions, with
      the strongest heat effects in London and strongest cold effects in the Eastern
      region. For all regions, a mean relative risk of 1.03 (95% confidence interval
      (CI) 1.02 to 1.03) was estimated per degree increase above the heat threshold,
      defined as the 95th centile of the temperature distribution in each region, and
      1.06 (95% CI 1.05 to 1.06) per degree decrease below the cold threshold (set at
      the 5th centile). Elderly people, particularly those in nursing and care homes,
      were most vulnerable. The greatest risk of heat mortality was observed for
      respiratory and external causes, and in women, which remained after control for
      age. Vulnerability to either heat or cold was not modified by deprivation, except
      in rural populations where cold effects were slightly stronger in more deprived
      areas. CONCLUSIONS: Interventions to reduce vulnerability to both hot and cold
      weather should target all elderly people. Specific interventions should also be
      developed for people in nursing and care homes as heat illness is easily
      preventable.

PMID- 16990294
TI  - Hope and advance care planning in patients with end stage renal disease:
      qualitative interview study.
AB  - OBJECTIVE: To understand hope in the context of advance care planning from the
      perspective of patients with end stage renal disease. DESIGN: Qualitative in
      depth interview study. SETTING: Outpatient department of a university affiliated
      nephrology programme. PARTICIPANTS: 19 patients with end stage renal disease
      purposively selected from the renal insufficiency, haemodialysis, and peritoneal
      dialysis clinics. RESULTS: Patients' hopes were highly individualised and were
      shaped by personal values. They reflected a preoccupation with their daily lives.
      Participants identified hope as central to the process of advance care planning
      in that hope helped them to determine future goals of care and provided insight
      into the perceived benefits of advance care planning and their willingness to
      engage in end of life discussions. More information earlier in the course of the
      illness focusing on the impact on daily life, along with empowerment of the
      patient and enhancing professional and personal relationships, were key factors
      in sustaining patients' ability to hope. This helped them to imagine
      possibilities for a future that were consistent with their values and hopes. The
      reliance on health professionals to initiate end of life discussions and the
      daily focus of clinical care were seen as potential barriers to hope.
      CONCLUSIONS: Facilitated advance care planning through the provision of timely
      appropriate information can positively enhance rather than diminish patients'
      hope. Current practices concerning disclosure of prognosis are ethically and
      psychologically inadequate in that they do not meet the needs of patients.

PMID- 16990295
TI  - Acupuncture in mainstream health care.

PMID- 16990296
TI  - Childhood pneumonia in developing countries.

PMID- 16990297
TI  - Caesarean delivery in the second stage of labour.

PMID- 16990298
TI  - Emergency naloxone for heroin overdose.

PMID- 16990299
TI  - Teratogenicity of antiepileptic drugs.

PMID- 16990302
TI  - Gulf war symptoms do not constitute a syndrome.

PMID- 16990303
TI  - British soldiers are "guinea pigs" for new use of blood clotting agent.

PMID- 16990305
TI  - Inquiry opens into state of childhood in the UK.

PMID- 16990304
TI  - Try psychology before drugs for children with mental problems.

PMID- 16990309
TI  - Challenge food industry to improve Scots' diet, says review.

PMID- 16990310
TI  - No progress in reducing childhood obesity despite increased awareness, report
      says.

PMID- 16990311
TI  - Indian association questions plan for hepatitis B immunisation.

PMID- 16990317
TI  - Poorest areas have best smoking cessation services, report shows.

PMID- 16990318
TI  - Outpatient thyroidectomy is safe in selected patients.

PMID- 16990319
TI  - WHO recommends DDT to control malaria.

PMID- 16990323
TI  - A patient's journey: living with paranoid schizophrenia.

PMID- 16990322
TI  - Oral malodour (halitosis).

PMID- 16990324
TI  - Problem drug use.

PMID- 16990325
TI  - ABC of obesity. Obesity--time to wake up.

PMID- 16990326
TI  - Who's kicking who?

PMID- 16990327
TI  - Race and mental health: there is more to race than racism.

PMID- 16990328
TI  - Acute appendicitis: weighing up risks and benefits of investigations and
      treatments.

PMID- 16990329
TI  - Acute appendicitis: leaving normal looking appendices.

PMID- 16990330
TI  - Stabbing: data support public perception.

PMID- 16990331
TI  - Acute renal failure from contrast medium: ... and remember simple and cheap
      measures.

PMID- 16990332
TI  - Acute renal failure from contrast medium: beware patients taking metformin...

PMID- 16990333
TI  - Acute appendicitis: acute appendicitis or acute appendicectomy?

PMID- 16990334
TI  - Possible cause of false normal B-12 assays.

PMID- 16990335
TI  - Society's advice on low weight and IVF was ignored by media.

PMID- 16990336
TI  - Benign prostatic hyperplasia: caveat for finasteride should be discussed before
      prescribing.

PMID- 16990337
TI  - More on switching statins: comments from Pfizer.

PMID- 16990338
TI  - Ageism in services for transient ischaemic attack and stroke: ageism or cost
      benefit analysis?

PMID- 16990339
TI  - Ageism in services for transient ischaemic attack and stroke: clinical leadership
      is key in changing practice.

PMID- 16990340
TI  - Long term safety of statins should be monitored.

PMID- 16990342
TI  - The role of the glucocorticoid receptor in mineralocorticoid/salt-mediated
      cardiac fibrosis.
AB  - The pathophysiological consequences of excess mineralocorticoid for salt status
      include hypertension, vascular inflammation, and cardiac fibrosis.
      Mineralocorticoid receptor (MR) blockade can both prevent and reverse established
      inflammation and fibrosis due to exogenous mineralocorticoids or endogenous
      glucocorticoid activation of the MR. Glucocorticoids also exert potent
      antiinflammatory effects via glucocorticoid receptors (GR) in the vascular wall.
      We propose that GR signaling may ameliorate mineralocorticoid/salt-induced
      vascular inflammation and fibrosis in the mineralocorticoid/salt model. In the
      present study, the role of GR in the mineralocorticoid/salt model was explored in
      uninephrectomized rats that were maintained on 0.9% saline solution to drink and
      treated as follows: control (CON), no further treatment; deoxycorticosterone
      (DOC; 20 mg/wk) for 4 wk (DOC4); DOC for 8 wk (DOC8); DOC for 8 wk plus the GR
      antagonist RU486 (2 mg/d) wk 5-8 (DOC8/RU486); and DOC for 8 wk plus RU486 and
      the MR antagonist eplerenone (EPL; 50 mg/kg.d) for wk 5-8 (DOC8/RU486+EPL). DOC
      treatment significantly increased systolic blood pressure, cardiac fibrosis,
      inflammation (ED-1-positive macrophages and osteopontin), and mRNA for markers of
      oxidative stress (p22phox, gp91phox, and NAD(P)H-4). GR blockade reduced the DOC
      mediated increase in systolic blood pressure and the number of infiltrating ED-1
      positive macrophages but had no effect on fibrosis, oxidative stress, or
      osteopontin mRNA levels. EPL reversed DOC-induced pathology in the absence or
      presence of GR blockade. Thus, blocking agonist activity at the GR neither
      enhances nor attenuates the fibrotic response, although it may modulate systolic
      blood pressure and macrophage recruitment in the mineralocorticoid/salt model.

PMID- 16990341
TI  - Regulation of adenosine 5',monophosphate-activated protein kinase and lipogenesis
      by androgens contributes to visceral obesity in an estrogen-deficient state.
AB  - Menopause is associated with an accumulation of visceral fat. An emerging concept
      suggests that relatively elevated levels of circulating androgens, compared with
      estrogens in postmenopausal women, underlie this shift in body fat distribution.
      In this study we administered dihydrotestosterone (DHT) to ovariectomized mice to
      examine the effect of relative androgen excess on adipose tissue distribution and
      function in estrogen-deficient mice. Compared with controls, DHT-treated mice
      exhibited increased body weight and visceral fat mass associated with
      triglyceride accumulation. Phosphorylation of AMP-activated protein kinase (AMPK)
      and acetyl CoA carboxylase was significantly decreased by DHT in visceral fat. In
      3T3-L1 cells, DHT decreased phosphorylation of AMPK in a dose-dependent manner.
      In addition, DHT increased the expression of lipogenic genes (fatty acid
      synthase, sterol regulatory element binding protein-2, and lipoprotein lipase) in
      visceral fat. These data provide the first in vivo evidence that an increased
      androgen to estrogen ratio can promote visceral fat accumulation by inhibiting
      AMPK activation and stimulating lipogenesis.

PMID- 16990343
TI  - Insulin growth factor-I and epidermal growth factor receptors recruit distinct
      upstream signaling molecules to enhance AKT activation in mammary epithelial
      cells.
AB  - IGF-I and epidermal growth factor (EGF) stimulate both normal mammary epithelial
      cell (MEC) growth and tumorigenesis. Whereas both growth factors increase DNA
      synthesis in MECs, how they evoke a greater response in combination when they
      activate similar signaling pathways remains unknown. In the present study, we
      investigated the signaling pathways by which these mitogens act in concert to
      increase DNA synthesis. Only EGF activated the MAPK pathway, and no further
      increase in MAPK activation was observed when both mitogens were added together.
      Both growth factors activated the phosphatidylinositol-3 kinase pathway, and
      simultaneous treatment enhanced phosphorylation of both AKT and its downstream
      target, p70S6K. The enhanced activation of AKT was observed at multiple time
      points (5 and 15 min) and growth factor concentrations (2.5-100 ng/ml). IGF-I
      activated AKT via insulin receptor substrate-1 and p85, the regulatory subunit of
      phosphatidylinositol-3 kinase. Treatment with EGF had no effect on insulin
      receptor substrate-1; however, it activated the EGF receptor, SHC, and c-Src. EGF
      treatment caused the association of SHC with Grb2 and Gab2 with phospho-SHC,
      phospho-Gab1, Grb2, and p85. Interestingly, inhibition of Src activation blocked
      the ability of EGF, but not IGF-I, to activate AKT. This corresponded with a
      decrease in phosphorylation of the EGF receptor and its association with phospho
      SHC as well as downstream signaling. Unexpectedly, inhibition of Src increased
      basal MAPK activation. This is the first study to show that EGF and IGF-I use
      separate upstream components within a given MEC line to enhance AKT
      phosphorylation, contributing to increased DNA synthesis.

PMID- 16990344
TI  - Thyroid hormone induction of actin polymerization in somatotrophs of hypothyroid
      rats: potential repercussions in growth hormone synthesis and secretion.
AB  - Thyroid hormone was shown to induce actin cytoskeleton polymerization in
      hypothyroid astrocytes and osteoblastic cells by a nongenomic mechanism.
      Polyadenylation of GH mRNA, a process that depends on cytoskeleton-associated
      proteins, was also shown to be regulated by thyroid hormone. Here we investigated
      by histochemistry and immunohistochemistry whether acute (100 microg per 100 g
      body weight, iv, for 30 min) or chronic (5 microg per 100 g body weight, ip, 5 d)
      administration of T3 to thyroidectomized (Tx) and sham-operated rats affects the
      somatotrophs F-actin cytoskeleton arrangement and its potential repercussion on
      GH synthesis and secretion. Thyroidectomy dramatically decreased the amount of
      somatotrophs F-actin content and induced the disassembly of the actin
      cytoskeleton. These effects were reversed by acute and chronic administration of
      T3. In addition, in Tx rat somatotrophs, GH labeling was detected mostly at the
      cell periphery. After 30 min of T3 administration, GH labeling decreased at
      periphery and increased in the perinuclear region, suggesting that GH secretion
      and synthesis were stimulated by T3. No differences were detected in the total
      actin protein content, although a decrease in the F- and increase in G-actin
      contents were detected in Tx rat pituitaries, a panorama that was reversed by
      acute T3 treatment, as shown by Western blotting analysis. The sham-operated
      animals' somatotrophs were only mildly affected by acute T3 administration. The
      results indicate that the T3-induced rapid alterations on somatotroph actin
      cytoskeleton and GH cellular distribution resulted from actin filaments
      rearrangement, which characterizes a nongenomic action.

PMID- 16990345
TI  - Regulation of Cdx2 expression by promoter methylation, and effects of Cdx2
      transfection on morphology and gene expression of human esophageal epithelial
      cells.
AB  - Caudal-related homeobox 2 (Cdx2) has been suggested as an early marker of
      Barrett's esophagus (BE), which is the premalignant lesion of esophageal
      adenocarcinoma (EAC). However, the mechanism of ectopic Cdx2 expression in the
      esophageal epithelial cells and its role in the development of BE remained
      unclear. RT-PCR, pyrosequencing and methylation-specific PCR were used to
      determine expression and promoter methylation of Cdx2 in human esophageal
      epithelial cells (HET1A and SEG1) after treatment with 5-aza-2'-deoxycytidine
      (DAC), acid, bile acids and their combination. HET1A cells with stable
      transfection of Cdx2 were characterized for morphology and gene expression
      profiles with Affymetrix array. We found Cdx2 was expressed in most human EAC
      cell lines, but not in squamous epithelial cell lines. DAC-induced demethylation
      and expression of Cdx2 in HET1A and SEG1 cells, and treatment with a DNA
      methylating agent counteracted the effect of DAC. Treatment of HET1A and SEG1
      cells with acid, bile acids or both also resulted in promoter demethylation and
      expression of Cdx2. HET1A cells with stable transfection of human Cdx2 formed
      crypt-like structures in vitro. Microarray analysis and quantitative real-time
      PCR showed that stable transfection of Cdx2 up-regulated differentiation markers
      of intestinal columnar epithelial cells and goblet cells in HET1A cells. This may
      be partially due to modulation of Notch signaling pathway, as western blotting
      confirmed down-regulation of Hes1 and up-regulation of Atoh1 and Muc2. Our data
      suggest that exposure to acid and/or bile acids may activate Cdx2 expression in
      human esophageal epithelial cells through promoter demethylation, and ectopic
      Cdx2 expression in esophageal squamous epithelial cells may contribute to
      intestinal metaplasia of the esophagus.

PMID- 16990346
TI  - Cancer stem cells--perspectives on current status and future directions: AACR
      Workshop on cancer stem cells.

PMID- 16990348
TI  - CW-OSL measurement protocols using optical fibre Al2O3:C dosemeters.
AB  - A new system for in vivo dosimetry during radiotherapy has been introduced.
      Luminescence signals from a small crystal of carbon-doped aluminium oxide
      (Al2O3:C) are transmitted through an optical fibre cable to an instrument that
      contains optical filters, a photomultiplier tube and a green (532 nm) laser. The
      prime output is continuous wave optically stimulated luminescence (CW-OSL) used
      for the measurement of the integrated dose. We demonstrate a measurement protocol
      with high reproducibility and improved linearity, which is suitable for clinical
      dosimetry. A crystal-specific minimum pre-dose is necessary for signal
      stabilisation. Simple background subtraction only partially removes the residual
      signal present at long integration times. Instead, the measurement protocol
      separates the decay curve into three individual components and only the fast and
      medium components were used.

PMID- 16990347
TI  - Structure and function relations with a T-cell-activating polysaccharide antigen
      using circular dichroism.
AB  - Studies centered on understanding how molecular structure affects biological
      function have historically focused on proteins. Circular dichroism (CD) is
      commonly used to analyze protein secondary structure, yet its application to
      other molecules is far less explored. In fact, little is known about how glycan
      conformation might affect function, likely because of a lack of tools for
      measuring dynamic structural changes of carbohydrates. In the present study, we
      developed a method based on CD to monitor conformational changes in the
      zwitterionic T-cell-activating glycoantigen polysaccharide A1 (PSA). We found
      that PSA helical structure produces a CD spectrum that is strikingly similar to
      proteins rich in alpha-helical content and is equally sensitive to nonpolar
      solvents. Like conventional T-cell-dependent proteins, PSA requires processing
      before major histocompatibility complex class II (MHCII) binding. CD spectra of
      PSA fragments of varying sizes indicated that fragments smaller than three
      repeating units lack helical content and are incapable of MHCII binding.
      Likewise, neutralization of charged groups in the repeating unit resulted in
      major conformational changes as measured by CD, which correlated with a lack of
      MHCII presentation. These data represent two significant findings: CD can be used
      to measure conformational changes in carbohydrates and the functional epitope
      from PSA is dependent on a specific conformation that is stabilized by adjacent
      repeating units and a zwitterionic charge motif. As a result, this work
      demonstrates that CD is a valuable tool for use in functional glycomics efforts
      that seek to align chemical and conformational structure with biological
      activity.

PMID- 16990349
TI  - Thermal pre-treatment in the OSL dating of quartz: is it necessary?
AB  - Thermal treatment before optically stimulated luminescence (OSL) measurement is
      an important step in all widely accepted OSL dating procedures used with quartz.
      This is a major constraint on the design of a portable luminescence instrument
      for estimating ages in the field. Preliminary experiments show that using a
      standard dating protocol without heating caused a 30-50% underestimation of
      equivalent dose. This underestimate arises mainly from OSL derived from the 110
      degrees C thermoluminescence (TL) trap; because of the thermal instability of
      this trap, this OSL contribution is only present in unheated laboratory
      regenerated signals, but not in the natural signal. An alternative to thermal pre
      treatment is investigated, based on the mathematical separation of the stable
      dosimetry OSL signal from the total OSL; the latter is the sum of signals from
      several traps, including the 110 degrees C TL trap. Our results show consistency
      with dose estimates obtained using a standard measurement protocol including pre
      heating.

PMID- 16990350
TI  - The natural history of Noonan syndrome: a long-term follow-up study.
AB  - OBJECTIVE: To define better the adult phenotype and natural history of Noonan
      syndrome. DESIGN: A prospective observational study of a large cohort. RESULTS:
      Data are presented for 112 individuals with Noonan syndrome (mean age 25.3 (range
      12-71) years), who were followed up for a mean of 12.02 years. Mutations in
      PTPN11 were identified in 35% of probands. Ten subjects died during the study
      interval; three of these deaths were secondary to heart failure associated with
      hypertrophic cardiomyopathy. Pulmonary stenosis affected 73 (65%) subjects; 42
      (58%) required no intervention, nine underwent balloon pulmonary valvuloplasty
      (three requiring further intervention) and 22 surgical valvuloplasty (three
      requiring further intervention). Hypertrophic cardiomyopathy affected 21 (19%)
      patients, which had remitted in two cases, but one subject required cardiac
      transplant. No subjects died suddenly or had symptoms suggestive of arrhythmia.
      The mean final adult height was 167.4 cm in males and 152.7 cm in females.
      Feeding problems in infancy were identified as a predictor of future outcome. The
      mean age of speaking in two-word phrases was 26 months for those with no feeding
      difficulties, compared with 39 months for those with severe problems requiring
      nasogastric feeding. Attendance at a school for children with special needs for
      the same groups was 12.5% and 58%, respectively. A statement of special
      educational need had been issued in 44% overall; however, academic achievement
      was broadly similar to that of the general population. IMPLICATIONS: Although the
      morbidity for some patients with Noonan syndrome is low, early predictors of
      poorer outcome have been identified, which will help ascertain those most in need
      of intervention.

PMID- 16990351
TI  - New knowledge, new insights, and new recommendations.

PMID- 16990352
TI  - Health and social care service changes: the potential to increase inequalities.

PMID- 16990354
TI  - Tumorous xanthomas in a young male with familial hypercholesterolaemia.

PMID- 16990353
TI  - Very high dose inhaled corticosteroids: panacea or poison?

PMID- 16990355
TI  - Extreme subcutaneous emphysema of eyelids.

PMID- 16990356
TI  - The pathophysiology of coronary artery aneurysms in Kawasaki disease: role of
      matrix metalloproteinases.
AB  - Kawasaki disease is an acute inflammatory syndrome that takes the form of
      systemic vasculitis, and predominantly affects children. Important complications
      of this disease are coronary artery dilation and aneurysm formation. Recent
      studies indicate that Kawasaki disease patients have elevated expression,
      activity, or protein levels of matrix metalloproteinases (MMPs), and suggest that
      imbalances in MMPs or MMP/tissue inhibitor of MMP (TIMP) play important
      pathophysiological roles in the development of coronary artery lesions in this
      disease. However, it remains unclear whether MMP activities at the site of
      coronary artery lesions are indeed increased. Further studies on the effects of
      MMP inhibition on coronary outcome are needed to define the roles of MMPs and
      TIMPs in the formation of coronary artery lesions in Kawasaki disease; findings
      of such studies may support the use of MMP inhibitors for the prevention of
      coronary artery complications in patients with this disease.

PMID- 16990357
TI  - The investigation and management of chronic neutropenia in children.
AB  - Unravelling the cause of a neutropenia poses a complex diagnostic challenge. The
      differential diagnosis ranges from life threatening disease to transient benign
      causes of little clinical significance. This review offers a practical guide to
      investigating the neutropenic child, and highlights features that merit
      specialist referral. Therapeutic options, the role of long term follow up, and
      the complications of severe chronic neutropenia are considered.

PMID- 16990360
TI  - Should children with ADHD and normal intelligence be routinely screened for
      underlying cytogenetic abnormalities?

PMID- 16990361
TI  - Is injection of botulinum toxin type A effective in the treatment of drooling in
      children with cerebral palsy?

PMID- 16990362
TI  - Should bubble baths be avoided in children with urinary tract infections?

PMID- 16990363
TI  - After the Court of Appeal: R v Harris and others [2005] EWCA crim 1980.

PMID- 16990364
TI  - Life threatening hypernatraemic dehydration in breast fed babies.

PMID- 16990365
TI  - The code on competing interests of the ACP.

PMID- 16990366
TI  - The emerging role of neuronal nitric oxide synthase in the regulation of
      myocardial function.
AB  - The recent discovery of a NOS1 gene product (i.e. a neuronal-like isoform of
      nitric oxide synthase or nNOS) in the mammalian left ventricular (LV) myocardium
      has provided a new key for the interpretation of the complex experimental
      evidence supporting a role for myocardial constitutive nitric oxide (NO)
      production in the regulation of basal and beta-badrenergic cardiac function.
      Importantly, nNOS gene deletion has been associated with more severe LV
      remodelling and functional deterioration in murine models of myocardial
      infarction, suggesting that nNOS-derived NO may also be involved in the
      myocardial response to injury. To date, the mechanisms by which nNOS influences
      myocardial pathophysiology remain incompletely understood. In particular, it
      seems over simplistic to assume that all aspects of the myocardial phenotype of
      nNOS knockout (nNOS(-/-)) mice are a direct consequence of lack of NO production
      from this source. Emerging data showing co-localisation of xanthine
      oxidoreductase (XOR) and nNOS in the sarcoplasmic reticulum of rodents, and
      increased XOR activity in the nNOS(-/-) myocardium, suggest that nNOS gene
      deletion may have wider implications on the myocardial redox state. Similarly,
      the mechanisms regulating the targeting of myocardial nNOS to different
      subcellular compartments and the functional consequences of intracellular nNOS
      trafficking have not been fully established. Whether this information could be
      translated into a better understanding and management of human heart failure
      remains the most important challenge for future investigations.

PMID- 16990367
TI  - Ovarian hormone status and skeletal muscle inflammation during recovery from
      disuse in rats.
AB  - Resumption of normal muscle loading after a period of disuse initiates cellular
      processes related to mass accretion. The renewed loading also induces a
      significant amount of muscle damage and subsequent inflammation. Ovarian hormone
      depletion delays atrophied myofibre mass recovery. Ovarian hormones are also
      global regulators of immune system function. The purpose of this study was to
      determine whether ovarian hormone depletion-induced deficits in myofibre regrowth
      after disuse atrophy are related to the induction of muscle damage and the
      associated inflammatory response. We hypothesized that soleus muscle immune cell
      infiltration and inflammatory gene expression would be both accentuated and
      prolonged in ovarian hormone-depleted rats during the first week of recovery from
      disuse atrophy. Intact and ovariectomized (OVX) female rats were subjected to
      hindlimb suspension for 10 days and then returned to normal ambulation for a
      recovery period, the rats were killed and the soleus muscle removed for analysis.
      Although reloading increased both circulating creatine kinase and myofibre
      membrane disruption, there was no effect of ovarian hormones on these processes
      during recovery. Muscle neutrophil concentration was increased above baseline
      regardless of hormone status at days 1 and 3 of recovery; however, this increase
      was 43% greater at day 3 in the OVX group. Muscle ED1+ and ED2+ macrophage
      concentrations were increased during recovery in both groups. However, macropage
      concentrations remained elevated at day 7 of recovery in the OVX group, whereas
      they returned to control levels in the intact group. Cyclo-oxygenase-2,
      interleukin-6 and interleukin-1beta muscle mRNA expression increased similarly
      during recovery, regardless of ovarian hormone status. These results demonstrate
      that the initial myofibre damage and inflammatory gene expression induced during
      muscle recovery from disuse atrophy are independent of ovarian hormone status.

PMID- 16990368
TI  - Follow-up of early unilateral nephrectomy for hypertension.
AB  - Early unilateral nephrectomy was carried out in four young children with
      unilateral renovascular disease, a poorly functioning kidney and hypertension. At
      follow-up 5-16 years later all showed normal growth, blood pressure and renal
      function, and only one child had low-grade albuminuria. Unilateral nephrectomy
      seems to be a safe and effective alternative to long-term hypotensive treatment.

PMID- 16990369
TI  - Renovascular hypertension commencing during fetal life.
AB  - We report three infants with severe, early hypertension due to unilateral
      renovascular disease, whose cardiovascular changes, or polycythaemia, or both,
      indicated they had been affected as fetuses. All underwent unilateral
      nephrectomy, and had a similar histology, with patchy areas having relatively
      normal glomeruli but immature proximal tubules. This pattern may be a marker for
      renovascular disease in fetal life.

PMID- 16990370
TI  - The role of abscisic acid and low temperature in chickpea (Cicer arietinum) cold
      tolerance. II. Effects on plasma membrane structure and function.
AB  - The frost hardiness of many plants such as chickpea can be increased by exposure
      to low non-freezing temperatures and/or the application of abscisic acid (ABA), a
      process known as frost acclimation. Experiments were conducted to study the
      response over a 14 d period of enriched plasma membrane fractions isolated from
      chickpea plants exposed to low temperature and sprayed with exogenous ABA.
      Measurement of the temperatures inducing 50% foliar cell death (LT50), and
      subsequent statistical analysis suggest that, like many plants, exposure to low
      temperatures (5/-2 degrees C; day/night) induces a significant level (P <0.05) of
      frost acclimation in chickpea when compared with control plants (20/7 degrees C;
      day/night). Spraying plants with exogenous ABA also increased frost tolerance (P
      <0.05), but was not as effective as low temperature-induced frost acclimation.
      Both pre-exposure to low temperatures and pre-treatment with ABA increased the
      levels of fatty acid desaturation in the plasma membrane (measured as the double
      bond index, DBI). Exposure of chickpea plants to low temperatures increased the
      DBI by 15% at day 4 and 19% at day 14 when compared with untreated control
      plants. Application of ABA alone did not increase the DBI by more than 6% at any
      time; the effects of both treatments applied together was more than additive,
      inducing a DBI increase of 27% at day 14 when compared with controls. There was a
      good correlation (P <0.05) between the DBI and LT50, suggesting that the presence
      of more unsaturated lipid in the plasma membrane may prevent cell lysis at low
      temperatures. Both pre-exposure to low, non-freezing temperatures and pre
      treatment with ABA induced measurable changes in membrane fluidity, but these
      changes did not correlate with changes in LT50, suggesting that physical
      properties of the plasma membrane other than fluidity are involved in frost
      acclimation in chickpea.

PMID- 16990371
TI  - Arabidopsis thaliana avoids freezing by supercooling.
AB  - Arabidopsis thaliana (L.) Heynh. has been described as a freezing-tolerant
      species based on freezing-resistance assays. Nonetheless, this type of experiment
      does not discriminate between freezing-tolerance and freezing-avoidance
      mechanisms. The purpose of this paper was to determine which of these two
      freezing-resistance mechanisms is responsible for freezing resistance in A.
      thaliana. This was achieved by comparing the thermal properties (ice-nucleation
      temperature and the freezing temperature) of leaves and the lethal temperature to
      10, 50 and 90% of the plants (LT10, LT50, and LT90, respectively). Two wild-type
      genotypes were used (Columbia and Ler) and their mutants (esk-1 and frs-1,
      respectively), which differ in their freezing resistance. This study's results
      indicated that the mutant esk-1, described as a freezing-tolerant species showed
      freezing tolerance only after a cold-acclimation period. The mutant frs-1,
      described as freezing sensitive, presented freezing avoidance. Both wild
      genotypes presented LT50 similar to or higher than the ice-nucleation
      temperature. Thus, the main freezing-resistance mechanism for A. thaliana is
      avoidance of freezing by supercooling. No injury of the photosynthetic apparatus
      was shown by measuring the maximal photochemical efficiency (Fv/Fm) and pigments
      (chlorophyll and carotenoid) during cold acclimation in all genotypes. During
      cold acclimation, Columbia and esk-1 increased total soluble carbohydrates in
      leaves. esk-1 was the only genotype that presented freezing tolerance after cold
      acclimation. This feature could be related to an increase in sugar accumulation
      in the apoplast.

PMID- 16990372
TI  - Hyperspectral remote sensing of plant pigments.
AB  - The dynamics of pigment concentrations are diagnostic of a range of plant
      physiological properties and processes. This paper appraises the developing
      technologies and analytical methods for quantifying pigments non-destructively
      and repeatedly across a range of spatial scales using hyperspectral remote
      sensing. Progress in deriving predictive relationships between various
      characteristics and transforms of hyperspectral reflectance data are evaluated
      and the roles of leaf and canopy radiative transfer models are reviewed.
      Requirements are identified for more extensive intercomparisons of different
      approaches and for further work on the strategies for interpreting canopy scale
      data. The paper examines the prospects for extending research to the wider range
      of pigments in addition to chlorophyll, testing emerging methods of hyperspectral
      analysis and exploring the fusion of hyperspectral and LIDAR remote sensing. In
      spite of these opportunities for further development and the refinement of
      techniques, current evidence of an expanding range of applications in the
      ecophysiological, environmental, agricultural, and forestry sciences highlights
      the growing value of hyperspectral remote sensing of plant pigments.

PMID- 16990373
TI  - Comparing regional transcript profiles from maize primary roots under well
      watered and low water potential conditions.
AB  - Regionally distinct elongation responses to water stress in the maize primary
      root tip have been observed in the past. A genetic basis for such differential
      responses has been demonstrated. Normalized bar-coded cDNA libraries were
      generated for four regions of the root tip, 0-3 mm (R1), 3-7 mm (R2), 7-12 mm
      (R3), and 12-20 mm (R4) from the root apex, and transcript profiles for these
      regions were sampled. This permitted a correlation between transcript nature and
      regional location for 15 726 expressed sequence tags (ESTs) that, in
      approximately equal numbers, derived from three conditions of the root: water
      stress (water potential: -1.6 MPa) for 5 h and for 48 h, respectively, and well
      watered (5 h and 48 h combined). These normalized cDNA libraries provided 6553
      unigenes. An analysis of the regional representation of transcripts showed that
      populations were largely unaffected by water stress in R1, correlating with the
      maintenance of elongation rates under water stress known for R1. In contrast,
      transcript profiles in regions 2 and 3 diverged in well-watered and water
      stressed roots. In R1, transcripts for translation and cell cycle control were
      prevalent. R2 was characterized by transcripts for cell wall biogenesis and
      cytoskeleton formation. R3 and R4 shared prevalent groups of transcripts
      responsible for defence mechanisms, ion transport, and biogenesis of secondary
      metabolites. Transcripts which were followed for 1, 6, and 48 h of water stress
      showed distinct region-specific changes in absolute expression and changes in
      regulated functions.

PMID- 16990374
TI  - Ethylene-dependent and -independent pathways controlling floral abscission are
      revealed to converge using promoter::reporter gene constructs in the ida
      abscission mutant.
AB  - The process of floral organ abscission in Arabidopsis thaliana can be modulated
      by ethylene and involves numerous genes contributing to cell separation. One gene
      that is absolutely required for abscission is INFLORESCENCE DEFICIENT IN
      ABSCISSION, IDA, as the ida mutant is completely blocked in abscission. To
      elucidate the genetic pathways regulating floral abscission, molecular markers
      expressed in the floral abscission zone have been studied in an ida mutant
      background. Using plants with promoter-reporter gene constructs including
      promoters of a novel FLORAL ABSCISSION ASSOCIATED gene (FAA) encoding a putative
      single-stranded binding protein (BASIL), chitinase (CHIT::GUS) and cellulase
      (BAC::GUS), it is shown that IDA acts in the last steps of the abscission
      process. These markers, as well as HAESA, encoding a receptor-like kinase, were
      unaffected in their temporal expression patterns in ida compared with wild-type
      plants; thus showing that different regulatory pathways are active in the
      abscission process. In contrast to BASIL, CHIT::GUS and BAC::GUS showed, however,
      much weaker induction of expression in an ida background, consistent with a
      reduction in pathogen-associated responses and a lack of total dissolution of
      cell walls in the mutant. IDA, encoding a putative secreted peptide ligand, and
      HAESA appeared to have identical patterns of expression in floral abscission
      zones. Lastly, to address the role of ethylene, IDA::GUS expression in the wild
      type and the ethylene-insensitive mutant etr1-1 was compared. Similar temporal
      patterns, yet restricted spatial expression patterns were observed in etr1-1,
      suggesting that the pathways regulated by IDA and by ethylene act in parallel,
      but are, to some degree, interdependent.

PMID- 16990375
TI  - Tissue-specific expression of tomato Ribonuclease LX during phosphate starvation
      induced root growth.
AB  - Ribonuclease LX (RNaseLX) from tomato (Solanum lycopersicum L.) belongs to the
      RNase T2/S-RNase superfamily of plant endoribonucleases and this is a report on
      the characterization of the RNaseLX gene and its encoded protein as a member of
      the phosphate starvation response in tomato. RNaseLX gene sequences were cloned
      by a PCR-assisted approach. RNaseLX promoter sequences contained the conserved
      binding motif of the transcription factor PHR1 known to mediate phosphate
      starvation-dependent gene expression. The increase of RNaseLX transcript levels
      in roots during phosphate starvation correlated with high promoter activity in
      transgenic plants carrying a PromLX::uidA gene construct and pointed to
      transcriptional control of RNaseLX expression. Histochemical staining for beta
      glucuronidase activity and immunodetection of RNaseLX protein revealed striking
      RNaseLX expression in main and lateral root tips of phosphate-starved transgenic
      plants, specifically in epidermal cells, as well as in lateral and adventitious
      root primordia. Induced RNaseLX expression in roots correlated with stimulated
      growth and elongation of primary and lateral roots during phosphate deprivation.
      Phosphate-starvation-induced RNaseLX transcript levels in roots were not
      modulated by auxin or ethylene. These data indicate that the role of
      intracellular RNaseLX in the phosphate starvation response is connected with
      specific RNA turnover processes at the root tip.

PMID- 16990376
TI  - The plant ER-Golgi interface: a highly structured and dynamic membrane complex.
AB  - As compared with other eukaryotic cells, plants have developed an endoplasmic
      reticulum (ER)-Golgi interface with very specific structural characteristics. ER
      to Golgi and Golgi to ER transport appear not to be dependent on the
      cytoskeleton, and ER export sites have been found closely associated with Golgi
      bodies to constitute entire mobile units. However, the molecular machinery
      involved in membrane trafficking seems to be relatively conserved among
      eukaryotes. Therefore, a challenge for plant scientists is to determine how these
      molecular machineries work in a different structural and dynamic organization.
      This review will focus on some aspects of membrane dynamics that involve coat
      proteins, SNAREs (soluble N-ethylmaleimide-sensitive factor attachment receptor
      proteins), lipids, and lipid-interacting proteins.

PMID- 16990377
TI  - Progress and challenges in studies of the evolution of development.
AB  - Plant evolutionary developmental genetics (EDG) has made considerable progress
      over the last decade. This is in part due to the accumulation of large amounts of
      sequence data that have provided robust organismal phylogenies and, increasingly,
      broad assessments of molecular evolution. Attempts to use primary sequence data
      to identify genes that have changed function in evolutionary time have not been
      as successful as initially hoped. The coding sequences of most genes, which are
      more amenable to statistical analysis than are regulatory sequences, are
      generally under purifying selection, as would be expected if much evolutionary
      change is the result of changes in cis-regulatory sequences. Sequence-based
      analysis of the regulatory sequences themselves remains difficult. Comparative
      studies of gene expression have been useful to identify genes whose developmental
      role may have changed in evolutionary time and will be critical to the future
      development of EDG. Such studies can be used to test hypotheses of gene function.
      Transformation experiments are often illuminating, but can be hard to interpret,
      particularly if genes from multiple species are all placed into a single
      heterologous system such as Arabidopsis. The ideal experiment would be a gene
      swap or promoter swap between two species, but this awaits development of good
      transformation systems. The immediate need for EDG is studies of gene expression
      on a massive scale, far broader than any studies undertaken to date.

PMID- 16990378
TI  - Audio interview: pay for performance--recommendations of the Institute of
      Medicine, with Dr. Elliott S. Fisher and Dr. Karen Davis interviewed by Rachel
      Gotbaum.

PMID- 16990379
TI  - Images in clinical medicine. Uni-, bi-, tri-, and quadricuspid aortic valves.

PMID- 16990380
TI  - The politics and promise of stem-cell research.

PMID- 16990381
TI  - Bit player or powerhouse? China and stem-cell research.

PMID- 16990382
TI  - Telomeres, telomerase, and human disease.

PMID- 16990383
TI  - Intracoronary injection of mononuclear bone marrow cells in acute myocardial
      infarction.
AB  - BACKGROUND: Previous studies have shown improvement in left ventricular function
      after intracoronary injection of autologous cells derived from bone marrow (BMC)
      in the acute phase of myocardial infarction. We designed a randomized, controlled
      trial to further investigate the effects of this treatment. METHODS: Patients
      with acute ST-elevation myocardial infarction of the anterior wall treated with
      percutaneous coronary intervention were randomly assigned to the group that
      underwent intracoronary injection of autologous mononuclear BMC or to the control
      group, in which neither aspiration nor sham injection was performed. Left
      ventricular function was assessed with the use of electrocardiogram-gated single
      photon-emission computed tomography (SPECT) and echocardiography at baseline and
      magnetic resonance imaging (MRI) 2 to 3 weeks after the infarction. These
      procedures were repeated 6 months after the infarction. End points were changes
      in the left ventricular ejection fraction (LVEF), end-diastolic volume, and
      infarct size. RESULTS: Of the 50 patients assigned to treatment with mononuclear
      BMC, 47 underwent intracoronary injection of the cells at a median of 6 days
      after myocardial infarction. There were 50 patients in the control group. The
      mean (+/-SD) change in LVEF, measured with the use of SPECT, between baseline and
      6 months after infarction for all patients was 7.6+/-10.4 percentage points. The
      effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage
      point (95% confidence interval [CI], -3.4 to 4.6; P=0.77) on SPECT, an increase
      of 0.6 percentage point (95% CI, -2.6 to 3.8; P=0.70) on echocardiography, and a
      decrease of 3.0 percentage points (95% CI, 0.1 to -6.1; P=0.054) on MRI. The two
      groups did not differ significantly in changes in left ventricular end-diastolic
      volume or infarct size and had similar rates of adverse events. CONCLUSIONS: With
      the methods used, we found no effects of intracoronary injection of autologous
      mononuclear BMC on global left ventricular function.

PMID- 16990384
TI  - Intracoronary bone marrow-derived progenitor cells in acute myocardial
      infarction.
AB  - BACKGROUND: Pilot trials suggest that the intracoronary administration of
      autologous progenitor cells may improve left ventricular function after acute
      myocardial infarction. METHODS: In a multicenter trial, we randomly assigned 204
      patients with acute myocardial infarction to receive an intracoronary infusion of
      progenitor cells derived from bone marrow (BMC) or placebo medium into the
      infarct artery 3 to 7 days after successful reperfusion therapy. RESULTS: At 4
      months, the absolute improvement in the global left ventricular ejection fraction
      (LVEF) was significantly greater in the BMC group than in the placebo group (mean
      [+/-SD] increase, 5.5+/-7.3% vs. 3.0+/-6.5%; P=0.01). Patients with a baseline
      LVEF at or below the median value of 48.9% derived the most benefit (absolute
      improvement in LVEF, 5.0%; 95% confidence interval, 2.0 to 8.1). At 1 year,
      intracoronary infusion of BMC was associated with a reduction in the prespecified
      combined clinical end point of death, recurrence of myocardial infarction, and
      any revascularization procedure (P=0.01). CONCLUSIONS: Intracoronary
      administration of BMC is associated with improved recovery of left ventricular
      contractile function in patients with acute myocardial infarction. Large-scale
      studies are warranted to examine the potential effects of progenitor-cell
      administration on morbidity and mortality.

PMID- 16990385
TI  - Transcoronary transplantation of progenitor cells after myocardial infarction.
AB  - BACKGROUND: Pilot studies suggest that intracoronary transplantation of
      progenitor cells derived from bone marrow (BMC) or circulating blood (CPC) may
      improve left ventricular function after acute myocardial infarction. The effects
      of cell transplantation in patients with healed myocardial infarction are
      unknown. METHODS: After an initial pilot trial involving 17 patients, we randomly
      assigned, in a controlled crossover study, 75 patients with stable ischemic heart
      disease who had had a myocardial infarction at least 3 months previously to
      receive either no cell infusion (23 patients) or infusion of CPC (24 patients) or
      BMC (28 patients) into the patent coronary artery supplying the most dyskinetic
      left ventricular area. The patients in the control group were subsequently
      randomly assigned to receive CPC or BMC, and the patients who initially received
      BMC or CPC crossed over to receive CPC or BMC, respectively, at 3 months' follow
      up. RESULTS: The absolute change in left ventricular ejection fraction was
      significantly greater among patients receiving BMC (+2.9 percentage points) than
      among those receiving CPC (-0.4 percentage point, P=0.003) or no infusion (-1.2
      percentage points, P<0.001). The increase in global cardiac function was related
      to significantly enhanced regional contractility in the area targeted by
      intracoronary infusion of BMC. The crossover phase of the study revealed that
      intracoronary infusion of BMC was associated with a significant increase in
      global and regional left ventricular function, regardless of whether patients
      crossed over from control to BMC or from CPC to BMC. CONCLUSIONS: Intracoronary
      infusion of progenitor cells is safe and feasible in patients with healed
      myocardial infarction. Transplantation of BMC is associated with moderate but
      significant improvement in the left ventricular ejection fraction after 3 months.

PMID- 16990386
TI  - The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.
AB  - BACKGROUND: We tested the safety and efficacy of eculizumab, a humanized
      monoclonal antibody against terminal complement protein C5 that inhibits terminal
      complement activation, in patients with paroxysmal nocturnal hemoglobinuria
      (PNH). METHODS: We conducted a double-blind, randomized, placebo-controlled,
      multicenter, phase 3 trial. Patients received either placebo or eculizumab
      intravenously; eculizumab was given at a dose of 600 mg weekly for 4 weeks,
      followed 1 week later by a 900-mg dose and then 900 mg every other week through
      week 26. The two primary end points were the stabilization of hemoglobin levels
      and the number of units of packed red cells transfused. Biochemical indicators of
      intravascular hemolysis and the patients' quality of life were also assessed.
      RESULTS: Eighty-seven patients underwent randomization. Stabilization of
      hemoglobin levels in the absence of transfusions was achieved in 49% (21 of 43)
      of the patients assigned to eculizumab and none (0 of 44) of those assigned to
      placebo (P<0.001). During the study, a median of 0 units of packed red cells was
      administered in the eculizumab group, as compared with 10 units in the placebo
      group (P<0.001). Eculizumab reduced intravascular hemolysis, as shown by the
      85.8% lower median area under the curve for lactate dehydrogenase plotted against
      time (in days) in the eculizumab group, as compared with the placebo group
      (58,587 vs. 411,822 U per liter; P<0.001). Clinically significant improvements
      were also found in the quality of life, as measured by scores on the Functional
      Assessment of Chronic Illness Therapy-Fatigue instrument (P<0.001) and the
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire. Of the 87 patients, 4 in the eculizumab group and 9 in the placebo
      group had serious adverse events, none of which were considered to be treatment
      related; all these patients recovered without sequelae. CONCLUSIONS: Eculizumab
      is an effective therapy for PNH.

PMID- 16990387
TI  - Clinical practice. Acute vulvovaginitis.

PMID- 16990388
TI  - Cancer stem cells.

PMID- 16990389
TI  - Images in clinical medicine. Regression of optociliary shunt vessels.

PMID- 16990390
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 29-2006. A 43-year-old woman with painful nodules on the
      fingertips, shortness of breath, and fatigue.

PMID- 16990391
TI  - Cardiac cell therapy--mixed results from mixed cells.

PMID- 16990392
TI  - Stimulatory autoantibodies to the PDGF receptor in scleroderma.

PMID- 16990393
TI  - ACE inhibitors and major congenital malformations.

PMID- 16990394
TI  - Omalizumab for asthma.

PMID- 16990395
TI  - Medical mystery: Abnormal chest film--the answer.

PMID- 16990396
TI  - Obesity and public health law.

PMID- 16990397
TI  - Positive Clostridium difficile stool assay in a patient with fatal C. sordellii
      infection.

PMID- 16990398
TI  - Stoichiometry of a pore mutation that abolishes picrotoxin-mediated antagonism of
      the GABAA receptor.
AB  - Picrotoxin, a potent antagonist of the inhibitory central nervous system GABAA
      and glycine receptors, is believed to interact with residues that line the
      central ion pore. These pore-lining residues are in the second transmembrane
      domain (TM2) of each of the five constituent subunits. One of these amino acids,
      a threonine at the 6' location, when mutated to phenylalanine, abolishes
      picrotoxin sensitivity. It has been suggested that this threonine, via hydrogen
      bonding, directly interacts with the picrotoxin molecule. We previously
      demonstrated that this mutation, in the alpha, beta or gamma subunit, can impart
      picrotoxin resistance to the GABA receptor. Since the functional pentameric GABA
      receptor contains two alpha subunits, two beta subunits and one gamma subunit, it
      is not clear how many alpha and beta subunits must carry this mutation to impart
      the resistant phenotype. In this study, by coexpression of mutant alpha or beta
      subunits with their wild-type counterparts in various defined ratios, we
      demonstrate that any single subunit carrying the 6' mutation imparts picrotoxin
      resistance. Implications of this finding in terms of the mechanism of antagonism
      are considered.

PMID- 16990399
TI  - Temperature- and exercise-induced gene expression and metabolic enzyme changes in
      skeletal muscle of adult zebrafish (Danio rerio).
AB  - Both exercise training and cold acclimatization induce muscle remodelling in
      vertebrates, producing a more aerobic phenotype. In ectothermic species exercise
      training and cold-acclimatization represent distinct stimuli. It is currently
      unclear if these stimuli act through a common mechanism or if different
      mechanisms lead to a common phenotype. The goal of this study was to survey
      responses that represent potential mechanisms responsible for contraction- and
      temperature-induced muscle remodelling, using an ectothermic vertebrate. Separate
      groups of adult zebrafish (Danio rerio) were either swim trained or cold
      acclimatized for 4 weeks. We found that the mitochondrial marker enzyme citrate
      synthase (CS) was increased by 1.5x in cold and by 1.3x with exercise (P<0.05).
      Cytochrome c oxidase (COx) was increased by 1.2x following exercise training
      (P<0.05) and 1.2x (P=0.07) with cold acclimatization. However, only cold
      acclimatization increased beta-hydroxyacyl-CoA dehydrogenase (HOAD) compared to
      exercise-trained (by 1.3x) and pyruvate kinase (PK) relative to control
      zebrafish. We assessed the whole-animal performance outcomes of these treatments.
      Maximum absolute sustained swimming speed (Ucrit) was increased in the exercise
      trained group but not in the cold acclimatized group. Real-time PCR analysis
      indicated that increases in CS are primarily transcriptionally regulated with
      exercise but not with cold treatments. Both treatments showed increases in
      nuclear respiratory factor (NRF)-1 mRNA which was increased by 2.3x in cold
      acclimatized and 4x in exercise-trained zebrafish above controls. In contrast,
      peroxisome proliferator-activated receptor (PPAR)-alpha mRNA levels were
      decreased in both experimental groups while PPAR-beta1 declined in exercise
      training only. Moreover, PPAR-gamma coactivator (PGC)-1alpha mRNA was not changed
      by either treatment. In zebrafish, both temperature and exercise produce a more
      aerobic phenotype, but there are stimulus-dependent responses (i.e. HOAD and PK
      activities). While similar changes in NRF-1 mRNA suggest that common responses
      might underlie aerobic muscle remodelling there are distinct changes (i.e. CS and
      PPAR-beta1 mRNA) that contribute to specific temperature- and exercise-induced
      phenotypes.

PMID- 16990400
TI  - Pacemaker phase shift in the absence of neural activity in guinea-pig stomach: a
      microelectrode array study.
AB  - Gastrointestinal (GI) motility is well organized. GI muscles act as a functional
      syncytium to achieve physiological functions under the control of neurones and
      pacemaker cells, which generate basal spontaneous pacemaker electrical activity.
      To date, it is unclear how spontaneous electrical activities are coupled,
      especially within a micrometre range. Here, using a microelectrode array, we show
      a spatio-temporal analysis of GI spontaneous electrical activity. The muscle
      preparations were isolated from guinea-pig stomach, and fixed in a chamber with
      an array of 8 x 8 planar multielectrodes (with 300 microm in interpolar
      distance). The electrical activities (field potentials) were simultaneously
      recorded through a multichannel amplifier system after high-pass filtering at 0.1
      Hz. Dihydropyridine Ca(2+) channel antagonists are known to differentiate the
      electrical pacemaker activity of interstitial cells of Cajal (ICCs) by
      suppressing smooth muscle activity. In the presence of nifedipine, we observed
      spontaneous electrical activities that were well synchronized over the array
      area, but had a clear phase shift depending on the distance. The additional
      application of tetrodotoxin (TTX) had little effect on the properties of the
      electrical activity. Furthermore, by constructing field potential images, we
      visualized the synchronization of pacemaker electrical activities resolving phase
      shifts that were measurable over several hundred micrometres. The results imply a
      phase modulation mechanism other than neural activity, and we postulate that this
      mechanism enables smooth GI motility. In addition, some preparations clearly
      showed plasticity of the pacemaker phase shift.

PMID- 16990401
TI  - TRP channels and lipids: from Drosophila to mammalian physiology.
AB  - The transient receptor potential (TRP) ion channel family was the last major ion
      channel family to be discovered. The prototypical member (dTRP) was identified by
      a forward genetic approach in Drosophila, where it represents the transduction
      channel in the photoreceptors, activated downstream of a Gq-coupled PLC. In the
      meantime 29 vertebrate TRP isoforms are recognized, distributed amongst seven
      subfamilies (TRPC, TRPV, TRPM, TRPML, TRPP, TRPA, TRPN). They subserve a wide
      range of functions throughout the body, most notably, though by no means
      exclusively, in sensory transduction and in vascular smooth muscle. However,
      their precise physiological roles and mechanism of activation and regulation are
      still only gradually being revealed. Most TRP channels are subject to multiple
      modes of regulation, but a common theme amongst the TRPC/V/M subfamilies is their
      regulation by lipid messengers. Genetic evidence supports an excitatory role of
      diacylglycerol (DAG) for the dTRP's, although curiously only DAG metabolites
      (PUFAs) have been found to activate the Drosophila channels. TRPC2,3,6 and 7 are
      widely accepted as DAG-activated channels, although TRPC3 can also be regulated
      via a store-operated mechanism. More recently PIP2 has been shown to be required
      for activity of TRPV5, TRPM4,5,7 and 8, whilst it may inhibit TRPV1 and the
      dTRPs. Although compelling evidence for a direct interaction of DAG with the TRPC
      channels is lacking, mutagenesis studies have identified putative PIP2
      interacting domains in the C-termini of several TRPV and TRPM channels.

PMID- 16990402
TI  - Thyrotropin-releasing hormone increases GABA release in rat hippocampus.
AB  - Thyrotropin-releasing hormone (TRH) is a tripeptide that is widely distributed in
      the brain including the hippocampus where TRH receptors are also expressed. TRH
      has anti-epileptic effects and regulates arousal, sleep, cognition, locomotion
      and mood. However, the cellular mechanisms underlying such effects remain to be
      determined. We examined the effects of TRH on GABAergic transmission in the
      hippocampus and found that TRH increased the frequency of GABAA receptor-mediated
      spontaneous IPSCs in each region of the hippocampus but had no effects on
      miniature IPSCs or evoked IPSCs. TRH increased the action potential firing
      frequency recorded from GABAergic interneurons in CA1 stratum radiatum and
      induced membrane depolarization suggesting that TRH increases the excitability of
      interneurons to facilitate GABA release. TRH-induced inward current had a
      reversal potential close to the K+ reversal potential suggesting that TRH
      inhibits resting K+ channels. The involved K+ channels were sensitive to Ba2+ but
      resistant to other classical K+ channel blockers, suggesting that TRH inhibits
      the two-pore domain K+ channels. Because the effects of TRH were mediated via
      Galphaq/11, but were independent of its known downstream effectors, a direct
      coupling may exist between Galphaq/11 and K+ channels. Inhibition of the function
      of dynamin slowed the desensitization of TRH responses. TRH inhibited seizure
      activity induced by Mg2+ deprivation, but not that generated by picrotoxin,
      suggesting that TRH-mediated increase in GABA release contributes to its anti
      epileptic effects. Our results demonstrate a novel mechanism to explain some of
      the hippocampal actions of TRH.

PMID- 16990403
TI  - Structural changes in the myosin filament and cross-bridges during active force
      development in single intact frog muscle fibres: stiffness and X-ray diffraction
      measurements.
AB  - Structural and mechanical changes occurring in the myosin filament and myosin
      head domains during the development of the isometric tetanus have been
      investigated in intact frog muscle fibres at 4 degrees C and 2.15 microm
      sarcomere length, using sarcomere level mechanics and X-ray diffraction at
      beamline ID2 of the European Synchrotron Radiation Facility (Grenoble, France).
      The time courses of changes in both the M3 and M6 myosin-based reflections were
      recorded with 5 ms frames using the gas-filled RAPID detector (MicroGap
      Technology). Following the end of the latent period (11 ms after the start of
      stimulation), force increases to the tetanus plateau value (T(0)) with a half
      time of 40 ms, and the spacings of the M3 and M6 reflections (S(M3) and S(M6))
      increase by 1.5% from their resting values, with time courses that lead that of
      force by approximately 10 and approximately 20 ms, respectively. These temporal
      relations are maintained when the increase of force is delayed by approximately
      10 ms by imposing, from 5 ms after the first stimulus, 50 nm (half-sarcomere)(-1)
      shortening at the velocity (V(0)) that maintains zero force. Shortening at V(0)
      transiently reduces S(M3) following the latent period and delays the subsequent
      increase in S(M3), but only delays the S(M6) increase without a transient
      decrease. Shortening at V(0) imposed at the tetanus plateau causes an abrupt
      reduction of the intensity of the M3 reflection (I(M3)), whereas the intensity of
      the M6 reflection (I(M6)) is only slightly reduced. The changes in half-sarcomere
      stiffness indicate that the isometric force at each time point is proportional to
      the number of myosin heads bound to actin. The different sensitivities of the
      intensity and spacing of the M3 and M6 reflections to the mechanical responses
      support the view that the M3 reflection in active muscle originates mainly from
      the myosin heads attached to the actin filament and the M6 reflection originates
      mainly from a fixed structure in the myosin filament signalling myosin filament
      length changes during the tetanus rise.

PMID- 16990404
TI  - Vascular endothelial growth factor mRNA and protein do not change in parallel
      during non-inflammatory skeletal muscle ischaemia in rat.
AB  - Impaired blood flow is thought to induce a pro-angiogenic environment due to
      local hypoxia, yet prolonged mild ischaemia induces only modest capillary growth.
      We compared the expression of vascular endothelial growth factor (VEGF) mRNA and
      protein with capillary to fibre ratio (C: F) and muscle blood flow in extensor
      digitorum longus of rats that had undergone unilateral ligation of the common
      iliac artery. Resting blood flow during the first two weeks after ligation (3, 7
      and 14 days) was decreased by approximately 60% but recovered partially after 5
      weeks (36% reduction). Functional hyperaemia (9-fold increase in blood flow
      during contractions) was eliminated in the first week after ligation, with a
      moderate recovery seen after 14 and 35 days. Muscle histology confirmed the
      absence of tissue necrosis or inflammation. Both VEGF mRNA (60%, P<0.05) and
      protein levels (700%, P<0.01) increased during the initial phase of ischaemia (at
      1 and 3 days), well before any overt angiogenesis, and both declined towards
      control levels by 7 days. A secondary increase in VEGF protein (by 60% at 14
      days, P<0.05) preceded the 20% increase in C: F seen after 5 weeks, but occurred
      while VEGF transcript levels continued to decline (to 50% of control at 35 days,
      P<0.05). Thus, evaluation of neither VEGF mRNA nor protein is an adequate index
      of angiogenic potential in response to ischaemia. We conclude that VEGF alone is
      insufficient to induce angiogenesis in ischaemic conditions, and that effective
      angiotherapy requires intervention aimed at other cytokines.

PMID- 16990407
TI  - Involvement of interstitial cells of Cajal in the control of smooth muscle
      excitability. Proceedings of a symposium. July 22, 2006. Okayama, Japan.

PMID- 16990406
TI  - Prior heavy exercise elevates pyruvate dehydrogenase activity and speeds O2
      uptake kinetics during subsequent moderate-intensity exercise in healthy young
      adults.
AB  - The adaptation of pulmonary oxygen uptake (.VO2) during the transition to
      moderate-intensity exercise (Mod) is faster following a prior bout of heavy
      intensity exercise. In the present study we examined the activation of pyruvate
      dehydrogenase (PDHa) during Mod both with and without prior heavy-intensity
      exercise. Subjects (n = 9) performed a Mod(1)-heavy-intensity-Mod(2) exercise
      protocol preceded by 20 W baseline. Breath-by-breath .VO2 kinetics and near
      infrared spectroscopy-derived muscle oxygenation were measured continuously, and
      muscle biopsy samples were taken at specific times during the transition to Mod.
      In Mod(1), PDHa increased from baseline (1.08 +/- 0.2 mmol min(-1) (kg wet wt)(
      1)) to 30 s (2.05 +/- 0.2 mmol min(-1) (kg wet wt)(-1)), with no additional
      change at 6 min exercise (2.07 +/- 0.3 mmol min(-1) (kg wet wt)(-1)). In Mod(2),
      PDHa was already elevated at baseline (1.88 +/- 0.3 mmol min(-1) (kg wet wt)(-1))
      and was greater than in Mod(1), and did not change at 30 s (1.96 +/- 0.2 mmol
      min(-1) (kg wet wt)(-1)) but increased at 6 min exercise (2.70 +/- 0.3 mmol min(
      1) (kg wet wt)(-1)). The time constant of .VO2 was lower in Mod(2) (19 +/- 2 s)
      than Mod(1) (24 +/- 3 s). Phosphocreatine (PCr) breakdown from baseline to 30 s
      was greater (P < 0.05) in Mod(1) (13.6 +/- 6.7 mmol (kg dry wt)(-1)) than Mod(2)
      (6.5 +/- 6.2 mmol (kg dry wt)(-1)) but total PCr breakdown was similar between
      conditions (Mod(1), 14.8 +/- 7.4 mmol (kg dry wt)(-1); Mod(2), 20.1 +/- 8.0 mmol
      (kg dry wt)(-1)). Both oxyhaemoglobin and total haemoglobin were elevated prior
      to and throughout Mod(2) compared with Mod(1). In conclusion, the greater PDHa at
      baseline prior to Mod(2) compared with Mod(1) may have contributed in part to the
      faster .VO2 kinetics in Mod(2). That oxyhaemoglobin and total haemoglobin were
      elevated prior to Mod(2) suggests that greater muscle perfusion may also have
      contributed to the observed faster .VO2 kinetics. These findings are consistent
      with metabolic inertia, via delayed activation of PDH, in part limiting the
      adaptation of pulmonary .VO2 and muscle O2 consumption during the normal
      transition to exercise.

PMID- 16990405
TI  - Downregulation of tonic GABA currents following epileptogenic stimulation of rat
      hippocampal cultures.
AB  - Deficits in GABAergic inhibitory transmission are a hallmark of temporal lobe
      epilepsy and have been replicated in animal and tissue culture models of
      epilepsy. GABAergic inhibition comprises phasic and tonic inhibition that is
      mediated by synaptic and extrasynaptic GABAA receptors, respectively. We have
      recently demonstrated that chronic stimulation with cyclothiazide (CTZ) or kainic
      acid (KA) induces robust epileptiform activity in hippocampal neurons both in
      vitro and in vivo. Here, we report a downregulation of tonic GABA inhibition
      after chronic epileptogenic stimulation of rat hippocampal cultures. Chronic
      pretreatment of hippocampal neurons with CTZ or KA resulted in a marked reduction
      in GABAergic inhibition, as shown by a significant decrease in whole-cell GABA
      currents and in the frequency of miniature inhibitory postsynaptic currents
      (mIPSCs). Interestingly, synaptically localized GABAA receptors remained
      relatively stable, as evidenced by the unaltered amplitude of mIPSCs, as well as
      the unchanged punctate immunoreactivity of gamma2 subunit-containing postsynaptic
      GABAA receptors. In contrast, tonic GABA currents, assessed either by a GABAA
      receptor antagonist bicuculline or a selective extrasynaptic GABAA receptor
      agonist THIP, were significantly reduced following epileptogenic stimulation.
      These results reveal a novel form of neural plasticity, that epileptogenic
      stimulation can selectively downregulate extrasynaptic GABAA receptors while
      leaving synaptic GABAA receptors unchanged. Thus, in addition to synaptic
      alteration of GABAergic transmission, regulation of tonic inhibition may also
      play an important role during epileptogenesis.

PMID- 16990408
TI  - Dietary patterns and risk of colorectal tumors: a cohort of French women of the
      National Education System (E3N).
AB  - Little is known about the dietary patterns associated with colorectal tumors
      along the adenoma-carcinoma sequence. Scores for dietary patterns were obtained
      by factor analysis in women from the French cohort of the European Prospective
      Investigation into Cancer and Nutrition (1993-2000). Their association with
      colorectal tumors was investigated in 516 adenoma cases (175 high-risk adenomas)
      and 4,804 polyp-free women and in 172 colorectal cancer cases and 67,312 cancer
      free women. The authors identified four dietary patterns: "healthy" (vegetables,
      fruit, yogurt, sea products, and olive oil); "Western" (potatoes, pizzas and
      pies, sandwiches, sweets, cakes, cheese, cereal products, processed meat, eggs,
      and butter); "drinker" (sandwiches, snacks, processed meat, and alcoholic
      beverages); and "meat eaters" (meat, poultry, and margarine). For quartile 4
      versus quartile 1, an increased risk of adenoma was observed with high scores of
      the Western pattern (multivariate relative risk (RR) = 1.39, 95% confidence
      interval: 1.00, 1.94; p(trend) = 0.03) and the drinker pattern (RR = 1.42, 95%
      confidence interval: 1.10, 1.83; p(trend) = 0.01). The meat-eaters pattern was
      positively associated with colorectal cancer risk (for quartile 4 vs. quartile 1:
      RR = 1.58, 95% confidence interval: 0.98, 2.53; p(trend) = 0.02). Dietary
      patterns that reflect a Western way of life are associated with a higher risk of
      colorectal tumors.

PMID- 16990409
TI  - Genetic analysis of resistance to soybean mosaic virus in j05 soybean.
AB  - Soybean cultivar J05 was identified to be resistant to the most virulent strain
      of soybean mosaic virus (SMV) in northeastern China. However, the reaction of J05
      to SMV strains in the United States of America is unknown, and genetic
      information is needed to utilize this germplasm in a breeding program. The
      objectives of this study were to determine the reaction of J05 to all US strains
      of SMV (G1-G7), the inheritance of SMV resistance in J05, and the allelic
      relationship of resistance genes in J05 with other reported resistance genes. J05
      was crossed with susceptible cultivar Essex (rsv) to study the inheritance of SMV
      resistance. J05 was also crossed with PI 96983 (Rsv1), L29 (Rsv3), and V94-5152
      (Rsv4) to test the allelism of resistance genes. F(2) populations and F(2:3)
      lines from these crosses were inoculated with G1 or G7 in the greenhouse.
      Inheritance and allelism studies indicate that J05 possesses 2 independent
      dominant genes for SMV resistance, one at the Rsv1 locus conferring resistance to
      G1 and necrosis to G7 and the other at the Rsv3 locus conditioning resistance to
      G7 but susceptibility to G1. The presence of both genes in J05 provides
      resistance to G1 and G7. J05 is unique from the previous sources that carry 2
      genes of Rsv1Rsv3 and will be useful in breeding for SMV resistance.

PMID- 16990411
TI  - Association of adiponectin gene variations with risk of incident myocardial
      infarction and ischemic stroke: a nested case-control study.
AB  - BACKGROUND: Adiponectin (ADIPOQ) gene variations are associated with risk of
      cardiovascular disease in patients with diabetes. No prospective data are
      available, however, on the risk of atherothrombotic disorders in persons with
      ADIPOQ variations who do not have diabetes. METHODS: From a group of DNA samples
      collected at baseline in a prospective cohort of 14 916 initially healthy
      American men, we assessed the presence of 5 ADIPOQ genetic variants (rs266729,
      rs182052, rs822396, rs2241766, and rs1501299) in samples from 600 Caucasian men
      who subsequently suffered an atherothrombotic event (incident myocardial
      infarction or ischemic stroke) and from 600 age- and smoking-matched Caucasian
      men who remained free of reported vascular disease during follow-up (controls).
      RESULTS: Genotype distributions for the variations tested were in Hardy-Weinberg
      equilibrium. Marker-by-marker conditional logistic regression analysis, adjusted
      for potential risk factors, showed an association of rs266729 [recessive: odds
      ratio (OR), 0.26; 95% confidence interval (CI), 0.10-0.64; P=0.004] and rs182052
      (recessive: OR, 0.40; 95% CI, 0.21-0.76; P=0.006) with decreased risk of ischemic
      stroke. These findings remained significant after Bonferroni correction.
      Haplotype-based (constituted by rs266729, rs182052, and rs822396) conditional
      logistic regression analysis, adjusted for the same potential risk factors,
      showed an association of haplotype G-A-G (OR, 0.28; 95% CI, 0.09-0.87; P=0.03)
      with decreased risk of ischemic stroke. Prespecified analysis limited to
      participants without baseline diabetes showed similar significant findings.
      CONCLUSIONS: The present prospective investigation provides further evidence for
      a protective role of adiponectin gene variation in the risk of ischemic stroke
      that was independent of the presence of diabetes.

PMID- 16990410
TI  - Inhibitory effects of micronized fenofibrate on carotid atherosclerosis in
      patients with essential hypertension.
AB  - BACKGROUND: The coexistence of hypertension and dyslipidemia synergistically
      increases the risk of cardiovascular events. We investigated the effect of the
      lipid-lowering agent micronized fenofibrate on inhibition of carotid
      atherosclerosis in patients with essential hypertension and mild hyperlipidemia.
      METHODS: We measured serum lipid profiles and inflammatory markers on chemistry
      or immune analyzers and common or internal carotid intima-media thickness (IMT)
      and diameter (D) by ultrasonography. RESULTS: Patients receiving micronized
      fenofibrate for 24 months in addition to antihypertensive treatment had decreased
      concentrations of total cholesterol, LDL-cholesterol, triglyceride,
      apolipoprotein B100, oxidized LDL, high-sensitivity C-reactive protein, P
      selectin, and cytokines. These patients had increased concentrations of HDL
      cholesterol, apolipoprotein A-I, and nitric oxide. Common carotid artery IMT
      (CCAIMT) and internal carotid artery IMT (ICAIMT) remained unchanged during the
      24-month intervention. Moreover, the mean CCAIMT/D ratio and ICAIMT/D ratio were
      significantly decreased in the fenofibrate intervention group. In contrast,
      CCAIMT/D and ICAIMT/D ratios were increased in the control group. The incidence
      rates of carotid artery plaque formation and stroke in the fenofibrate
      intervention group were significantly lower than those in the control group.
      CONCLUSION: The combination of antihypertensive agents with micronized
      fenofibrate can effectively prevent the progression of carotid atherosclerosis
      and reduce the incidence of stroke in patients with essential hypertension.

PMID- 16990412
TI  - Lipoprotein(a) in the cerebrospinal fluid of neurological patients with blood
      cerebrospinal fluid barrier dysfunction.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized pathogenic particle in human
      plasma, but its presence in the cerebrospinal fluid and its possible role in the
      central nervous system have not been documented. We tested the hypothesis that
      apolipoprotein(a) [apo(a)], free or as a component of the Lp(a) particle, can
      cross the blood-cerebrospinal fluid barrier and be found in the cerebrospinal
      fluid of patients affected by neurologic pathologies. METHODS: We studied paired
      cerebrospinal fluid/serum samples from 77 patients with inflammatory (n=20) or
      noninflammatory (n=34) blood-cerebrospinal fluid barrier dysfunction and without
      blood-cerebrospinal fluid barrier dysfunction (n=23). We used ELISA to measure
      Lp(a) concentrations and Western blot and immunodetection to analyze apo(a)
      isoforms in native and reducing conditions. RESULTS: Entire Lp(a) with either
      small or large apo(a) isoforms was present in the cerebrospinal fluid of patients
      with blood-cerebrospinal fluid barrier dysfunction, regardless of its
      pathogenesis. Multiple linear regression analysis showed that both serum Lp(a)
      concentration (P=0.003) and cerebrospinal fluid/serum albumin ratio (P<0.001)
      were predictors of the Lp(a) concentration in cerebrospinal fluid. CONCLUSIONS:
      Our results demonstrate that Lp(a) can cross a dysfunctional blood-cerebrospinal
      fluid barrier. The unusual presence of Lp(a) in the cerebrospinal fluid could
      extend some of its known pathogenic effects to the central nervous system.

PMID- 16990415
TI  - Targeted gene-expression analysis by genome-controlled reverse transcription-PCR.
AB  - BACKGROUND: For gene-expression analysis, which is anticipated to play an
      important role in classification of tumors and premalignant conditions, PCR-based
      quantitative assays must have increased diagnostic quantitative accuracy and
      reproducibility and enable analysis of gene expression in formalin-fixed paraffin
      embedded (FFPE) tissue samples. METHODS: We developed a reverse transcription-PCR
      based quantitative assay that modifies the cDNA sequence to increase the melting
      temperature of short (56-64 bp) PCR amplicons, enabling their quantification in
      tube by homogeneous melting-curve analysis. We used this method to analyze the
      expression of 8 genes, 7 potential colon cancer markers, and 1 control in samples
      obtained from 3 colon carcinoma cell lines, endoscopic biopsy from 8 patients
      undergoing gastroscopy for Barrett esophagus, and archival FFPE and frozen tissue
      from 20 patients who underwent surgery for colon carcinoma. RESULTS: The
      detection limit of the assay, when optimized for FFPE samples, was 100 copies of
      cDNA, and the dynamic range was 3 orders of magnitude. A prototype assay
      containing a panel of 8 genes displayed good reproducibility compared with the
      commercially available TaqMan assay (interassay CVs, 5%-20% vs 7%-43%,
      respectively). Gene-expression analysis was performed successfully in 26 (96%) of
      27 endoscopic biopsy specimens, 30 (86%) of 35 archival FFPE samples, and 20
      (100%) of 20 archival frozen samples. CONCLUSIONS: This new technology combines
      the reproducibility of competitive PCR with accurate quantitative detection by in
      tube melting-curve analysis, enabling efficient analysis of mRNA profiles in
      samples with small numbers of cells or small amounts of tissue, as well as in
      archival FFPE tissues.

PMID- 16990413
TI  - Health outcomes categorized by current and previous definitions of acute
      myocardial infarction in an unselected cohort of troponin-naive emergency
      department patients.
AB  - BACKGROUND: In a population originally classified for acute myocardial infarction
      (AMI) by the World Health Organization (WHO) definition, we compared the health
      outcomes after retrospectively reclassifying with the European Society of
      Cardiology and the American College of Cardiology (ESC/ACC) AMI definition, using
      the peak cardiac troponin I (cTnI) concentrations. The health outcomes were based
      on the WHO definition and occurred in an era that preceded the use of cardiac
      troponin biomarkers. METHODS: For 448 patients who presented to the emergency
      department with symptoms suggestive of cardiac ischemia in 1996, we obtained data
      for all-cause mortality and recurrent AMI for up to 1 year after the initial
      presentation. We performed retrospective analysis of the patients' frozen plasma
      samples to measure cTnI (AccuTnI, Beckman Coulter). RESULTS: At 30, 120, and 360
      days, the risk for AMI/death in patients positive for AMI by only the ESC/ACC
      criteria was significantly lower than the risk in patients positive by both
      ESC/ACC and WHO criteria, and significantly higher than in patients negative
      according to both criteria. In a separate analysis, patients with a peak
      cTnI>0.10 microg/L were at greater risk for AMI/death than patients with cTnI
      concentrations of 0.04-0.10 microg/L. Patients negative by both definitions or
      with peak cTnI concentrations<0.04 microg/L had the highest event-free survival
      rates (92% and 94%, respectively) at 1 year. CONCLUSION: In a troponin-naive
      population, patients classified as positive for AMI by only the ESC/ACC criteria
      have a prognosis that appears to be intermediate between those classified
      positive by both the WHO and ESC/ACC definitions and those who meet neither
      criteria.

PMID- 16990414
TI  - Electron spin resonance spectroscopy of serum albumin: a novel new test for
      cancer diagnosis and monitoring.
AB  - BACKGROUND: Proteins released by tumor cells can bind to serum albumin, leading
      to structural and functional modifications. We used electron spin resonance (ESR)
      spectroscopy to measure these changes in serum albumin and evaluate their utility
      for the diagnosis and monitoring of cancer. METHODS: We used an ESR spectrometer
      and 16-doxyl stearic acid as spin probe to measure conformational changes in
      albumin in blood samples from a population of healthy donors and volunteers
      (n=349), patients with a wide variety of hematologic and nonhematologic
      malignancy (n=135), and patients with chronic diseases such as gastrointestinal
      and pulmonary disease, diabetes, and cirrhosis (n=91). We added differing amounts
      of 16-doxyl stearic acid spin probe in ethanol to 50 microL of serum from each
      patient to create 3 different aliquots that differed in concentration of spin
      probe and ethanol, then incubated the aliquots for 10 min at 37 degrees C with
      continuous shaking. We measured the ESR spectra of each aliquot in triplicate and
      used proprietary software (MedInnovation GmbH) to evaluate the ESR spectrum for
      differences between cancer patients and the other groups. RESULTS: The diagnostic
      sensitivity and specificity of this test were 87.4% and 95.7%, respectively, for
      differentiating healthy individuals from cancer patients and 87.4%, and 85.7% for
      differentiating cancer patients from chronic disease patients. Serial evaluation
      of albumin conformation changes in several patients followed during the course of
      their disease showed excellent agreement between the magnitude of abnormality in
      the ESR spectrum of albumin and clinical and pathologic estimates of disease
      severity. CONCLUSIONS: ESR spectroscopy of serum albumin is a sensitive and
      noninvasive technique that clearly demonstrates diagnostic utility in patients
      with cancer. This test also enables monitoring of the disease course through use
      of serial measurements.

PMID- 16990416
TI  - Chip electrophoresis as a method for quantifying total microalbuminuria.
AB  - BACKGROUND: Microalbuminuria is an important prognostic marker in diabetic
      nephropathy and cardiovascular disease. Initially, most commercial assays used
      immunoreactivity to quantify microalbuminuria; however, size-exclusion HPLC
      demonstrated the existence of nonimmunoreactive forms of albumin that may not be
      detected by immunoassay. Recent liquid chromatography tandem mass spectrometry
      analyses suggested that size-exclusion HPLC gave higher results attributable to
      other urine proteins coeluting with albumin. We describe an assay that measures
      total microalbuminuria (immunoreactive and nonimmunoreactive) without any
      discernable interference from other common urine proteins. METHODS: We used an
      automated chip electrophoresis system that utilized microfluidic separation
      technology and fluorescent sample detection. Each albumin specimen was mixed with
      the manufacturer's sample buffer in addition to a chicken albumin internal
      calibrator and then electrophoresed without additional reducing agents. RESULTS:
      With variable concentrations of bovine serum albumin normalized to a chicken
      albumin internal calibrator, the electrophoresis system was best fit with a
      polynomial (R2=0.9997; concentration range, 5-300 mg/L). The lower limit of
      detection was 5 mg/L. Interchip and intrachip variation studies conducted on
      patient urine demonstrated CVs of 3%-13%. The introduction of potentially
      interfering agents (i.e., molecular analytes, nonalbumin proteins) did not alter
      precision. Compared with immunoassay, the chip electrophoresis identified higher
      microalbuminuria concentrations in all urine samples. The method also clearly
      resolved the albumin peak from interfering proteins. CONCLUSIONS: Unlike
      immunoassay, chip electrophoresis can detect both immunoreactive and
      nonimmunoreactive forms of albumin. This system is a simple, robust method to
      quantify microalbuminuria with good sensitivity, precision, and accuracy.

PMID- 16990417
TI  - High-speed interferometric detection of label-free immunoassays on the biological
      compact disc.
AB  - BACKGROUND: We describe a direct-detection immunoassay that uses high-speed
      optical interferometry on a biological compact disc (BioCD). METHODS: We
      fabricated phase-contrast BioCDs from 100-mm diameter 1.1-mm thick borosilicate
      glass disks coated with a 10-layer dielectric stack of Ta2O5/SiO2 that serves as
      a mirror with a center wavelength at 635 nm. The final layer is a lambda/4 layer
      of SiO2 onto which protein patterns are immobilized through several different
      chemical approaches. Protein on the disc is scanned by a focused laser spot as
      the disc spins. Interaction of the light with the protein provides both a phase
      modulated signal and a local reference that are combined interferometrically to
      convert phase into intensity. A periodic pattern of protein on the spinning disc
      produces an intensity modulation as a function of time that is proportional to
      the surface-bound mass. The binding of antigen or antibodies is detected
      directly, without labels, by a change in the interferometric intensity. The
      technique is demonstrated with a reverse assay of immobilized rabbit and mouse
      IgG antigen incubated against anti-IgG antibody in a casein buffer. RESULTS: The
      signal increased with increased concentration of analyte. The current embodiment
      detected a concentration of 100 ng/L when averaged over approximately 3000 100
      micron-diameter protein spots. CONCLUSIONS: High-speed interferometric detection
      of label-free protein assays on a rapidly spinning BioCD is a high-sensitivity
      approach that is amenable to scaling up to many analytes.

PMID- 16990418
TI  - Circulating proteasomes are functional and have a subtype pattern distinct from
      20S proteasomes in major blood cells.
AB  - BACKGROUND: 20S proteasomes, the proteolytic core particles of the major
      intracellular protein degradative pathway, are potential disease markers because
      they are detectable in human plasma as circulating proteasomes and their
      concentrations are increased in patients suffering from various diseases. To
      investigate the origin of circulating proteasomes, we compared some of their
      features with those of proteasomes isolated from major blood cells. METHODS: We
      isolated circulating proteasomes from the plasma of 2 patients with rheumatoid
      arthritis and 2 with systemic lupus erythematosus and from human plasma from
      healthy donors. We purified the proteasomes to apparent homogeneity and then used
      electron microscopy for imaging and chromatography for subtype spectrum analysis.
      We compared subtype results with those from 20S proteasomes purified from 4 major
      blood cell populations. We also tested proteasomes for enzymatic activity and
      immunosubunit content. RESULTS: Circulating proteasomes from plasma of healthy
      donors and from patients with autoimmune disease were found to have the same size
      and shape as erythrocyte proteasomes, be proteolytically active, and contain
      standard- and immunosubunits. Chromatography revealed 6 circulating proteasome
      subtype peaks in healthy donor plasma and 7 in patient donor plasma. Proteasomes
      from erythrocytes had 3 subtype peaks and those of monocytes, T-lymphocytes, and
      thrombocytes each had 5 different subtype peaks. CONCLUSION: Circulating
      proteasomes were intact and enzymatically active in plasma from healthy donors
      and from patients with autoimmune disease. Because the subtype patterns of
      circulating proteasomes clearly differ from those of proteasomes from blood
      cells, these cells cannot be regarded as a major source of circulating
      proteasomes.

PMID- 16990419
TI  - Improvement of technical and analytical performance in DNA sequencing by external
      quality assessment-based molecular training.
AB  - BACKGROUND: From 2003 to 2005, the European Union supported the EQUAL-initiative
      to develop methodological external quality assessment (EQA) schemes for
      genotyping (EQUALqual), quantitative PCR (EQUALquant), and sequencing (EQUALseq).
      As a relevant part of the EQUALseq program, a training course was held subsequent
      to the first EQA Program (EQAP1). The success of this course was reassessed in a
      2nd EQUALseq round (EQAP2). METHODS: In September 2005, a 3-day training course
      took place. We invited 8 laboratories with below-average performance in EQAP1 to
      improve their methodological and analytical/proficiency skills by lectures and
      practical work. To compare the results of the pretraining and posttraining
      EQUALseq rounds, we distributed 2 samples used in the first EQUAL round, but this
      time we provided different oligonucleotide sets. We evaluated the results by
      means of a previously described scoring system. RESULTS: In EQAP2, 6 laboratories
      returned complete data sets, corresponding to an overall 14% of the 43
      laboratories that had finished EQAP1. The scoring results for samples A
      (P=0.0025) and B (P=0.0125) demonstrated a significant improvement in EQAP2.
      Overall, a substantial improvement of technical and interpretative skills was
      demonstrated (P=0.0051). In general, the workshop experience was highly rated by
      the participants. CONCLUSIONS: Methodologic EQAPs in DNA sequencing are
      appropriate tools to uncover strengths and weaknesses in both technique and
      proficiency, emphasizing the need for mandatory EQAPs. Training courses, together
      with 2nd-round reiterations, should be implemented into methodological EQAPs in
      molecular diagnostics to improve technical performance and proficiency in genetic
      testing.

PMID- 16990420
TI  - Rapid, simple, and sensitive immunoagglutination assay with SiO2 particles and
      quartz crystal microbalance for quantifying Schistosoma japonicum antibodies.
AB  - BACKGROUND: The resurgence of the parasitic disease schistosomiasis calls for
      more efficient diagnostic tests. We developed a rapid, simple, portable, and
      sensitive immunoagglutination assay that uses SiO(2) particles and quartz crystal
      microbalance (QCM) for quantifying Schistosoma japonicum (Sj) antibodies (SjAb).
      METHODS: We prepared submicrometer-sized silica particles derivatized with Sj
      antigens as replacements for traditional latex microspheres to specifically
      agglutinate in the presence of SjAb targets, and we used the QCM monitor to
      measure the resulting frequency shifts. We optimized the assay medium by adding
      poly(ethylene glycol) (PEG) as a response accelerator of immunoagglutination. To
      minimize or eliminate any nonspecific agglutination or adsorption interferences,
      we conducted appropriate sealing procedures separately for silica particles and
      the QCM probe. RESULTS: The measured frequency changes were linearly related to
      the SjAb concentrations in infected rabbit serum. The PEG-assisted
      immunoagglutination system was quantitatively sensitive to SjAb concentrations
      ranging from approximately 0.70 to 32.31 mg/L, with a detection limit of
      approximately 0.46 mg/L. The obtained linear regression equation was: y=43.61
      x+80.44 (r=0.9872). Several serum specimens were evaluated with the developed QCM
      immunoassay and the results were compared with ELISA, validating the feasibility
      of practical applications. CONCLUSIONS: This novel immunoagglutination-based QCM
      detection format is rapid, simple to use, and more portable than conventional
      diagnostic immunoassays, thus offering a promising alternative tool that can be
      used for point-of-care clinical diagnosis of schistosomiasis, particularly in
      epidemic situations.

PMID- 16990421
TI  - Factors affecting S-homocysteinylation of LDL apoprotein B.
AB  - BACKGROUND: Hyperhomocysteinemia is an important risk factor for vascular disease
      and atherosclerosis, but the mechanisms by which homocysteine exerts its
      deleterious effects are not known. Because oxidation and/or homocysteinylation
      may increase atherogenicity of LDL, we investigated S-homocysteinylation of LDL
      as a possible contributor to atherosclerosis pathogenesis. METHODS: We used
      capillary electrophoresis to measure LDL-bound thiols [homocysteine, cysteine
      (Cys), cysteinylglycine, glutathione, and glutamylcysteine] in 104 healthy study
      participants We also assessed total plasma thiol concentrations and lipid
      profiles. RESULTS: Our data suggest that apoprotein B (apoB)-cysteinylglycine
      (CysGly), apoB-Hcy, and apoB-Cys concentrations are markedly higher in men than
      in women. The percentage of CysGly and glutathione on apoB was higher than that
      of the same thiols in plasma, whereas the other thiols were markedly less
      prevalent in lipoprotein than in plasma. Pearson correlation showed that among
      all thiols, only total plasma Hcy is related to apoB-Hcy concentrations. Multiple
      correlation analysis confirmed that total Hcy was the most important determinant
      of apoB-Hcy. Age and LDL cholesterol also showed positive associations, but Cys
      and, mainly, CysGly were negatively associated with apoB-Hcy concentrations.
      CONCLUSIONS: apoB-Hcy derivative formation is mainly dependent on total
      homocysteine concentration. Increased cholesterol concentrations are related to
      increased apoB-Hcy. CysGly seems to compete with Hcy for binding to LDL
      apoprotein, suggesting that CysGly may protect against atherosclerosis by
      decreasing the concentrations of Hcy transferred by LDL from plasma to
      endothelial and subendothelial spaces.

PMID- 16990422
TI  - Adiponectin and leptin in maternal serum, cord blood, and breast milk.
AB  - BACKGROUND: The presence of the adipokines adiponectin and leptin in cord blood
      and placental and fetal tissues suggests a possible role in fetal development.
      METHODS: We measured concentrations of adiponectin and leptin in maternal serum,
      cord blood, and breast milk and examined their correlations within a large,
      population-based study. Between November 2000 and November 2001, we recruited all
      mothers and their newborns after delivery at the University of Ulm (Ulm,
      Germany). The current analysis included 766 mothers with available breast milk
      samples collected 6 weeks postpartum. Adipokine concentrations were measured with
      commercially available ELISAs (R&D Systems). RESULTS: Median adiponectin
      concentrations in maternal serum (n=713), cord blood (n=709), and breast milk
      (n=766) were 8.6 mg/L, 30.6 mg/L, and 10.9 microg/L, respectively. Median leptin
      concentrations were 12.8 microg/L in maternal serum, 7.8 microg/L in cord blood,
      and 174.5 ng/L in breast milk. Whereas increases in leptin concentrations with
      increasing birth weight, birth weight according to gestational age, and ponderal
      index were statistically significant in cord blood (all P values<0.0001), cord
      blood adiponectin was clearly related only to birth weight (P=0.0004).
      Concentrations of both adipokines were moderately correlated in breast milk and
      maternal serum (both Spearman rho values were 0.43; P<0.0001). CONCLUSIONS:
      Concentrations of adiponectin and leptin vary strongly in maternal serum, cord
      blood, and breast milk, with only moderate correlations between both adipokines
      in maternal serum and breast milk. The health implications of these patterns
      warrant further investigation.

PMID- 16990423
TI  - Direct-tissue SELDI-TOF mass spectrometry analysis: a new application for
      clinical proteomics.
AB  - BACKGROUND: New molecular profiling technologies can aid in analysis of small
      pathologic samples obtained by minimally invasive biopsy and may enable the
      discovery of key biomarkers synergistic with anatomopathologic analysis related
      to prognosis, therapeutic response, and innovative target validation. Thus
      proteomic analysis at the histologic level in healthy and pathologic settings is
      a major issue in the field of clinical proteomics. METHODS: We used surface
      enhanced laser desorption ionization-time-of-flight mass spectrometry (SELDI-TOF
      MS) technology with surface chromatographic subproteome enrichment and
      preservation of the spatial distribution of proteomic patterns to detect discrete
      modifications of protein expression. We performed in situ proteomic profiling of
      mouse tissue and samples of human cancer tissue, including brain and lung cancer.
      RESULTS: This approach permitted the discrimination of glioblastomas from
      oligodendrogliomas and led to the identification of 3 potential markers.
      CONCLUSION: Direct tissue proteomic analysis is an original application of SELDI
      TOF MS technology that can expand the use of clinical proteomics as a complement
      to the anatomopathological diagnosis.

PMID- 16990424
TI  - Measurement of urinary metanephrines to screen for pheochromocytoma in an
      unselected hospital referral population.
AB  - BACKGROUND: Despite the rarity of pheochromocytoma, diagnosis is important
      because of the dangers of uncontrolled severe hypertension and the availability
      of very effective surgical treatment. Urinary or plasma catecholamines or
      catecholamine derivatives are commonly used to screen for pheochromocytomas
      before imaging, but data from 24-h urinary metanephrine results, patient age, and
      sex may better predict tumors in populations with a low pretest probability.
      METHODS: We retrospectively studied outcomes of an unselected population (1819
      patients) referred to a tertiary hospital laboratory for urinary metanephrine
      testing and investigated the usefulness of some simple derivative measures for
      detecting pheochromocytoma. We normalized values for urinary 24-h excretion of
      metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and
      sex-specific reference range. We then compared pheochromocytoma prediction by the
      use of products of these normalized measures with the gold standard of biopsy
      confirmed tumor. RESULTS: The product of the excretion of normalized metanephrine
      (nMAD) and normalized normetanephrine (nNMT) (nMAD.nNMT) was a highly sensitive
      (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%.
      ROC curves were not improved by including the normalized 3-methoxytyramine
      concentrations in the product. The test for nMAD.nNMT gave higher sensitivity and
      specificity than the tests for either substance alone. CONCLUSION: The test for
      nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population
      with a low pretest probability.

PMID- 16990425
TI  - Component analysis of HPLC profiles of unique lipoprotein subclass cholesterols
      for detection of coronary artery disease.
AB  - BACKGROUND: Patients with coronary artery disease (CAD) are known to have several
      lipoprotein abnormalities. We examined plasma cholesterol concentrations of major
      lipoproteins and their subclasses, using a gel permeation HPLC, to establish an
      association between a lipoprotein subclass pattern and the presence of CAD.
      METHODS: We performed a simple and fully automated HPLC, followed by mathematical
      treatment on chromatograms, for measuring cholesterol concentrations of major
      lipoproteins and their subclasses in 62 male patients (45 with CAD and 17
      controls without CAD) who underwent cardiac catheterization. RESULTS: For major
      lipoprotein classes, the patient group had a significantly (P<0.05) higher LDL
      cholesterol (LDL-C) and lower HDL-cholesterol (HDL-C), but no difference in VLDL
      cholesterol (VLDL-C) concentrations. For lipoprotein subclasses, the patient
      group had a significantly higher small VLDL-C (mean particle diameter of 31.3 nm,
      P<0.001), small LDL-C (23.0 nm, P<0.05), and very small LDL-C (16.7-20.7 nm,
      P<0.001), but a significantly lower large HDL-C (12.1 nm, P<0.001)
      concentrations. Combined variables of "small VLDL-C+small LDL-C+very small LDL-C
      large HDL-C" differentiated the patient from the control group more clearly than
      single-subclass measurements or calculated traditional lipid markers.
      CONCLUSIONS: These results suggest the usefulness of multiple and simultaneous
      subclass analysis of proatherogenic and antiatherogenic lipoproteins and indicate
      that HPLC and its component analysis can be used for easy detection and
      evaluation of abnormal distribution of lipoprotein subclasses associated with
      CAD.

PMID- 16990426
TI  - Rapid detection and identification of clinically important bacteria by high
      resolution melting analysis after broad-range ribosomal RNA real-time PCR.
AB  - BACKGROUND: Broad-range PCR provides valuable information for detecting bacterial
      infections. This study assesses the combined use of broad-range real-time PCR and
      high-resolution melting analysis for rapid detection and identification of
      clinically important bacteria. METHODS: We subjected 46 bacterial culture
      colonies representing 25 clinically important bacterial species to LightCycler
      real-time PCR amplification of the 16S rRNA gene in the presence of LCGreen I
      fluorescent dye. We performed high-resolution melting analysis of the PCR
      products with the HR-1 instrument and used melting profiles as molecular
      fingerprints for bacterial species identification. We validated this method via
      assessment of 54 consecutive bacteria culture colonies obtained from a clinical
      microbiology laboratory. RESULTS: The 16S rRNA gene of all 25 bacterial species
      was amplifiable by this method, with PCR product lengths of 216 or 217 bp. Of the
      25 bacterial species, we identified 11 via a 1-step post-PCR high-resolution
      melting analysis. The remaining bacterial species were identified via the high
      resolution melting plots obtained by heteroduplex formation between the PCR
      products of the tested and reference bacterial species or by a 2nd real-time PCR
      targeting a different region of the 16S rRNA gene. A high-resolution melting
      database and a working protocol were established for identifying these 25
      bacterial species. In the validation assay, a 94% accuracy rate was achieved when
      the bacterial species were in the high-resolution melting database. CONCLUSIONS:
      This assay requires no multiplexing or hybridization probes and provides a new
      approach for bacterial species identification in a molecular diagnostic
      laboratory.

PMID- 16990427
TI  - Reproducibility of risk figures in 2nd-trimester maternal serum screening for
      down syndrome: comparison of 2 laboratories.
AB  - BACKGROUND: Analytical error affects 2nd-trimester maternal serum screening for
      Down syndrome risk estimation. We analyzed the between-laboratory reproducibility
      of risk estimates from 2 laboratories. METHODS: Laboratory 1 used Bayer ACS180
      immunoassays for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG),
      Diagnostic Systems Laboratories (DSL) RIA for unconjugated estriol (uE3), and DSL
      enzyme immunoassay for inhibin-A (INH-A). Laboratory 2 used Beckman immunoassays
      for AFP, hCG, and uE3, and DSL enzyme immunoassay for INH-A. Analyte medians were
      separately established for each laboratory. We used the same computational
      algorithm for all risk calculations, and we used Monte Carlo methods for computer
      modeling. RESULTS: For 462 samples tested, risk figures from the 2 laboratories
      differed >2-fold for 44.7%, >5-fold for 7.1%, and >10-fold for 1.7%. Between
      laboratory differences in analytes were greatest for uE3 and INH-A. The screen
      positive rates were 9.3% for laboratory 1 and 11.5% for laboratory 2, with a
      significant difference in the patients identified as screen-positive vs screen
      negative (McNemar test, P<0.001). Computer modeling confirmed the large between
      laboratory risk differences. CONCLUSION: Differences in performance of assays and
      laboratory procedures can have a large effect on patient-specific risks.
      Screening laboratories should minimize test imprecision and ensure that each
      assay performs in a manner similar to that assumed in the risk computational
      algorithm.

PMID- 16990428
TI  - Detection of exon deletions within an entire gene (CFTR) by relative
      quantification on the LightCycler.
AB  - BACKGROUND: Cystic fibrosis (CF) is associated with at least 1 pathogen point
      sequence variant on each CFTR allele. Some symptomatic patients, however, have
      only 1 detectable pathogen sequence variant and carry, on the other allele, a
      large deletion that is not detected by conventional screening methods. METHODS:
      For relative quantitative real-time PCR detection of large deletions in the CFTR
      gene, we designed DNA-specific primers for each exon of the gene and primers for
      a reference gene (beta2-microglobulin). For PCR we used a LightCycler system
      (Roche) and calculated the gene-dosage ratio of CFTR to beta2-microglobulin. We
      tested the method by screening all 27 exons in 3 healthy individuals and 2
      patients with only 1 pathogen sequence variant. We then performed specific
      deletion screenings in 10 CF patients with known large deletions and a blinded
      analysis in which we screened 24 individuals for large deletions by testing 8 of
      27 exons. RESULTS: None of the ratios for control samples were false positive
      (for deletions or duplications); moreover, for all samples from patients with
      known large deletions, the calculated ratios for deleted exons were close to 0.5.
      In addition, the results from the blinded analysis demonstrated that our method
      can also be used for the screening of single individuals. CONCLUSIONS: The
      LightCycler assay allows reliable and rapid screening for large deletions in the
      CFTR gene and detects the copy number of all 27 exons.

PMID- 16990429
TI  - S100A4 accelerates tumorigenesis and invasion of human prostate cancer through
      the transcriptional regulation of matrix metalloproteinase 9.
AB  - We previously showed that the calcium-binding protein S100A4 is overexpressed
      during the progression of prostate cancer (CaP) in humans and in the TRAMP
      (transgenic adenocarcinoma of the mouse prostate) mouse model. We tested a
      hypothesis that the S100A4 gene plays a role in the invasiveness of human CaP and
      may be associated with its metastatic spread. We observed that siRNA-mediated
      suppression of the S100A4 gene significantly reduced the proliferative and
      invasive capability of the highly invasive CaP cells PC-3. We evaluated the
      mechanism through which the S100A4 gene controls invasiveness of cells by using a
      macroarray containing 96 well characterized metastatic genes. We found that
      matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1) were highly
      responsive to S100A4 gene suppression. Furthermore, S100A4 suppression
      significantly reduced the expression and proteolytic activity of MMP-9. By
      employing an MMP-9-promoter reporter, we observed a significant reduction in the
      transcriptional activation of the MMP-9 gene in S100A4-siRNA-transfected cells.
      Cells overexpressing the S100A4 gene (when transfected with pcDNA3.1-S100A4
      plasmid) also significantly expressed MMP-9 and TIMP-1 genes with increased
      proteolytic activity of MMP-9 concomitant to increased transcriptional activation
      of the MMP-9 gene. S100A4-siRNA-transfected cells exhibited a reduced rate of
      tumor growth under in vivo conditions. Our data demonstrate that the S100A4 gene
      controls the invasive potential of human CaP cells through regulation of MMP-9
      and that this association may contribute to metastasis of CaP cells. We suggest
      that S100A4 could be used as a biomarker for CaP progression and a novel
      therapeutic or chemopreventive target for human CaP treatment.

PMID- 16990430
TI  - Biological formation of ethane and propane in the deep marine subsurface.
AB  - Concentrations and isotopic compositions of ethane and propane in cold, deeply
      buried sediments from the southeastern Pacific are best explained by microbial
      production of these gases in situ. Reduction of acetate to ethane provides one
      feasible mechanism. Propane is enriched in (13)C relative to ethane. The amount
      is consistent with derivation of the third C from inorganic carbon dissolved in
      sedimentary pore waters. At typical sedimentary conditions, the reactions yield
      free energy sufficient for growth. Relationships with competing processes are
      governed mainly by the abundance of H(2). Production of C(2) and C(3)
      hydrocarbons in this way provides a sink for acetate and hydrogen but upsets the
      general belief that hydrocarbons larger than methane derive only from thermal
      degradation of fossil organic material.

PMID- 16990431
TI  - Sperm competition enhances functional capacity of mammalian spermatozoa.
AB  - When females mate promiscuously, sperm from rival males compete within the female
      reproductive tract to fertilize ova. Sperm competition is a powerful selective
      force that has shaped sexual behavior, sperm production, and sperm morphology.
      However, nothing is known about the influence of sperm competition on
      fertilization-related processes, because it has been assumed that sperm
      competition only involves a race to reach the site of fertilization. We compared
      four closely related rodent species with different levels of sperm competition to
      examine whether there are differences in the proportion of spermatozoa that
      become ready to interact with the ovum ("capacitated") and in the proportion of
      spermatozoa that experience the acrosome reaction in response to a natural
      stimulant. Our results show that differences between species in levels of sperm
      competition were associated with the proportion of spermatozoa that undergo
      capacitation and with the proportion of spermatozoa that respond to progesterone,
      an ovum-associated signal. Sperm competition thus favors a larger population of
      spermatozoa that are competent to fertilize, and spermatozoa that are more
      sensitive to the signals emitted by the ovum and that may penetrate the ova
      vestments more rapidly. These results suggest that, contrary to previous
      assumptions, competition between spermatozoa from rival males continues at the
      site of fertilization. These findings may have further evolutionary implications
      because the enhanced competitiveness of spermatozoa during fertilization may
      increase the risk of polyspermy to females. This could lead to antagonistic
      coevolution between the sexes and may contribute to the explanation of the rapid
      divergence observed in fertilization-related traits.

PMID- 16990432
TI  - Predicting interpretability of metabolome models based on behavior, putative
      identity, and biological relevance of explanatory signals.
AB  - Powerful algorithms are required to deal with the dimensionality of metabolomics
      data. Although many achieve high classification accuracy, the models they
      generate have limited value unless it can be demonstrated that they are
      reproducible and statistically relevant to the biological problem under
      investigation. Random forest (RF) generates models, without any requirement for
      dimensionality reduction or feature selection, in which individual variables are
      ranked for significance and displayed in an explicit manner. In metabolome
      fingerprinting by mass spectrometry, each metabolite can be represented by
      signals at several m/z. Exploiting a prior understanding of expected biochemical
      differences between sample classes, we aimed to develop meaningful metrics
      relevant to the significance both of the overall RF model and individual,
      potentially explanatory, signals. Pair-wise comparison of related plant genotypes
      with strong phenotypic differences demonstrated that robust models are not only
      reproducible but also logically structured, highlighting correlated m/z derived
      from just a small number of explanatory metabolites reflecting the biological
      differences between sample classes. RF models were also generated by using
      groupings of samples known to be increasingly phenotypically similar. Although
      classification accuracy was often reasonable, we demonstrated reproducibly in
      both Arabidopsis and potato a performance threshold based on margin statistics
      beyond which such models showed little structure indicative of either
      generalizability or further biological interpretability. In a multiclass problem
      using 25 Arabidopsis genotypes, despite the complicating effects of ecotype
      background and secondary metabolome perturbations common to several mutations,
      the ranking of metabolome signals by RF provided scope for deeper
      interpretability.

PMID- 16990433
TI  - An extensive repertoire of type III secretion effectors in Escherichia coli O157
      and the role of lambdoid phages in their dissemination.
AB  - Several pathogenic strains of Escherichia coli exploit type III secretion to
      inject "effector proteins" into human cells, which then subvert eukaryotic cell
      biology to the bacterium's advantage. We have exploited bioinformatics and
      experimental approaches to establish that the effector repertoire in the Sakai
      strain of enterohemorrhagic E. coli (EHEC) O157:H7 is much larger than previously
      thought. Homology searches led to the identification of >60 putative effector
      genes. Thirteen of these were judged to be likely pseudogenes, whereas 49 were
      judged to be potentially functional. In total, 39 proteins were confirmed
      experimentally as effectors: 31 through proteomics and 28 through translocation
      assays. At the protein level, the EHEC effector sequences fall into >20 families.
      The largest family, the NleG family, contains 14 members in the Sakai strain
      alone. EHEC also harbors functional homologs of effectors from plant pathogens
      (HopPtoH, HopW, AvrA) and from Shigella (OspD, OspE, OspG), and two additional
      members of the Map/IpgB family. Genes encoding proven or predicted effectors
      occur in >20 exchangeable effector loci scattered throughout the chromosome.
      Crucially, the majority of functional effector genes are encoded by nine
      exchangeable effector loci that lie within lambdoid prophages. Thus, type III
      secretion in E. coli is linked to a vast phage "metagenome," acting as a crucible
      for the evolution of pathogenicity.

PMID- 16990434
TI  - A Trojan horse transition state analogue generated by MgF3- formation in an
      enzyme active site.
AB  - Identifying how enzymes stabilize high-energy species along the reaction pathway
      is central to explaining their enormous rate acceleration. beta
      Phosphoglucomutase catalyses the isomerization of beta-glucose-1-phosphate to
      beta-glucose-6-phosphate and appeared to be unique in its ability to stabilize a
      high-energy pentacoordinate phosphorane intermediate sufficiently to be directly
      observable in the enzyme active site. Using (19)F-NMR and kinetic analysis, we
      report that the complex that forms is not the postulated high-energy reaction
      intermediate, but a deceptively similar transition state analogue in which
      MgF(3)(-) mimics the transferring PO(3)(-) moiety. Here we present a detailed
      characterization of the metal ion-fluoride complex bound to the enzyme active
      site in solution, which reveals the molecular mechanism for fluoride inhibition
      of beta-phosphoglucomutase. This NMR methodology has a general application in
      identifying specific interactions between fluoride complexes and proteins and
      resolving structural assignments that are indistinguishable by x-ray
      crystallography.

PMID- 16990435
TI  - Recruitment of dynein to the Jurkat immunological synapse.
AB  - Binding of T cells to antigen-presenting cells leads to the formation of the
      immunological synapse, translocation of the microtubule-organizing center (MTOC)
      to the synapse, and focused secretion of effector molecules. Here, we show that
      upon activation of Jurkat cells microtubules project from the MTOC to a ring of
      the scaffolding protein ADAP, localized at the synapse. Loss of ADAP, but not
      lymphocyte function-associated antigen 1, leads to a severe defect in MTOC
      polarization at the immunological synapse. The microtubule motor protein
      cytoplasmic dynein clusters into a ring at the synapse, colocalizing with the
      ADAP ring. ADAP coprecipitates with dynein from activated Jurkat cells, and loss
      of ADAP prevents MTOC translocation and the specific recruitment of dynein to the
      synapse. These results suggest a mechanism that links signaling through the T
      cell receptor to translocation of the MTOC, in which the minus end-directed motor
      cytoplasmic dynein, localized at the synapse through an interaction with ADAP,
      reels in the MTOC, allowing for directed secretion along the polarized
      microtubule cytoskeleton.

PMID- 16990437
TI  - Brain mechanisms mediating auditory attentional capture in humans.
AB  - The ability to detect and preferentially process salient auditory stimuli, even
      when irrelevant to a current task, is often critical for adaptive behavior. This
      stimulus-driven allocation of processing resources is known as "attentional
      capture." Here we used functional magnetic resonance imaging in humans to
      investigate brain activity and behavioral effects related to such auditory
      attentional capture. Participants searched a sequence of tones for a target tone
      that was shorter or longer than the nontarget tones. An irrelevant singleton
      feature in the tone sequence resulted in behavioral interference (attentional
      capture) and activation of parietal and prefrontal cortices only when the
      singleton was associated with a nontarget tone (nontarget singleton) and not when
      associated with a target tone (target singleton). In contrast, the presence (vs.
      absence) of a singleton feature in the sequence was associated with activation of
      frontal and temporal loci previously associated with auditory change detection.
      These results suggest that a ventral network involving superior temporal and
      inferior frontal cortices responds to acoustic variability, regardless of
      attentional significance, but a dorsal frontoparietal network responds only when
      a feature singleton captures attention.

PMID- 16990436
TI  - Quorum signal molecules as biosurfactants affecting swarming in Rhizobium etli.
AB  - Swarming motility is suggested to be a social phenomenon that enables groups of
      bacteria to coordinately and rapidly move atop solid surfaces. This multicellular
      behavior, during which the apparently organized bacterial populations are
      embedded in an extracellular slime layer, has previously been linked with biofilm
      formation and virulence. Many population density-controlled activities involve
      the activation of complex signaling pathways using small diffusible molecules,
      also known as autoinducers. In Gram-negative bacteria, quorum sensing (QS) is
      achieved primarily by means of N-acylhomoserine lactones (AHLs). Here, we report
      on a dual function of AHL molecules in controlling swarming behavior of Rhizobium
      etli, the bacterial symbiotic partner of the common bean plant. The major
      swarming regulator of R. etli is the cinIR QS system, which is specifically
      activated in swarming cells by its cognate AHL and other long-chain AHLs. This
      signaling role of long-chain AHLs is required for high-level expression of the
      cin and rai QS systems. Besides this signaling function, the long-chain AHLs also
      have a direct role in surface movement of swarmer cells as these molecules
      possess significant surface activity and induce liquid flows, known as Marangoni
      flows, as a result of gradients in surface tension at biologically relevant
      concentrations. These results point to an as-yet-undisclosed direct role of long
      chain AHL molecules as biosurfactants.

PMID- 16990438
TI  - The parahippocampal cortex mediates spatial and nonspatial associations.
AB  - The parahippocampal cortex (PHC) has been implicated in the processing of place
      related information. It has also been implicated in episodic memory, even for
      items that are not related to unique places. How could the same cortical region
      mediate such seemingly different cognitive processes? Both processes rely on
      contextual associations, and we therefore propose that the PHC should be viewed
      not as exclusively dedicated for analyzing place-related information, or as
      solely processing episodic memories, but instead as more generally playing a
      central role in contextual associative processing. To test this proposal, we
      created a novel learning paradigm to form new associations among meaningless
      visual patterns. These new associations were created to emulate either spatial or
      nonspatial contexts. Both spatial and nonspatial associations activated the PHC
      more than noncontextual items. Moreover, items from spatial contexts activated
      the posterior part of the PHC, whereas items from nonspatial contexts activated
      the anterior PHC. Therefore, we show that the PHC plays a role of processing
      contextual associations in general, and that these associations are not
      restricted to spatial information. By modifying the existing view of the PHC
      function accordingly, the seemingly contradicting processes that activate it can
      be reconciled under one overarching framework.

PMID- 16990439
TI  - The complete chloroplast genome of the chlorarachniophyte Bigelowiella natans:
      evidence for independent origins of chlorarachniophyte and euglenid secondary
      endosymbionts.
AB  - Chlorarachniophytes are amoeboflagellate cercozoans that acquired a plastid by
      secondary endosymbiosis. Chlorarachniophytes are the last major group of algae
      for which there is no completely sequenced plastid genome. Here we describe the
      69.2-kbp chloroplast genome of the model chlorarachniophyte Bigelowiella natans.
      The genome is highly reduced in size compared with plastids of other
      photosynthetic algae and is closer in size to genomes of several
      nonphotosynthetic plastids. Unlike nonphotosynthetic plastids, however, the B.
      natans chloroplast genome has not sustained a massive loss of genes, and it
      retains nearly all of the functional photosynthesis-related genes represented in
      the genomes of other green algae. Instead, the genome is highly compacted and
      gene dense. The genes are organized with a strong strand bias, and several
      unusual rearrangements and inversions also characterize the genome; notably, an
      inversion in the small-subunit rRNA gene, a translocation of 3 genes in the major
      ribosomal protein operon, and the fragmentation of the cluster encoding the large
      photosystem proteins PsaA and PsaB. The chloroplast endosymbiont is known to be a
      green alga, but its evolutionary origin and relationship to other primary and
      secondary green plastids has been much debated. A recent hypothesis proposes that
      the endosymbionts of chlorarachniophytes and euglenids share a common origin (the
      Cabozoa hypothesis). We inferred phylogenies using individual and concatenated
      gene sequences for all genes in the genome. Concatenated gene phylogenies show a
      relationship between the B. natans plastid and the ulvophyte-trebouxiophyte
      chlorophyte clade of green algae to the exclusion of Euglena. The B. natans
      plastid is thus not closely related to that of Euglena, which suggests that
      plastids originated independently in these 2 groups and the Cabozoa hypothesis is
      false.

PMID- 16990440
TI  - Polymorphisms in the HBB gene relate to individual cardiorespiratory adaptation
      in response to endurance training.
AB  - OBJECTIVE: The crucial role of haemoglobin in endurance performance has been well
      documented. We examined whether polymorphisms in the HBB gene modified aerobic
      capacity. METHODS: 102 recruits were trained by running 5000 m three times per
      week for 18 weeks. Exercise intensity progressively increased from an initial
      heart rate corresponding to 95% of the individual baseline ventilatory threshold
      during the first 10 weeks to 105% during the last 8 weeks. The phenotypes
      measured were running economy and VO(2)max. Running economy was determined by
      measuring submaximal VO(2) for 5 min at a constant running speed of 12 km.h(-1)
      and VO(2)max was obtained during an incremental test to exhaustion. Genomic DNA
      was extracted from white cells of peripheral blood and the -551C/T,
      intron2,+16C/G and +340 A/T genotypes were examined relative to the TAA site
      variants by PCR-RFLP. RESULTS: Genotype distributions were in Hardy-Weinberg
      equilibrium at three loci. None of the running economy and VO(2)max-related
      traits were associated with the three polymorphisms or haplotypes at baseline,
      while the training response of running economy was associated with -551C/T and
      intron2,+16C/G polymorphisms. Subjects homozygous for intron2,+16C/C or -551C/C
      had decreased oxygen cost of running compared to the other individuals.
      DISCUSSION: It was concluded that the -551C/C or intron2,+16C/C genotype might
      explain part of the individual variation in the cardiorespiratory adaptation to
      endurance training.

PMID- 16990441
TI  - Medial epicondylitis: is ultrasound guided autologous blood injection an
      effective treatment?
AB  - OBJECTIVE: To assess if ultrasound guided autologous blood injection is an
      effective treatment for medial epicondylitis. METHODS: Twenty patients (13 men, 7
      women) with refractory medial epicondylitis with symptom duration of 12 months
      underwent sonographic evaluation. Tendinosis was confirmed according to three
      sonographic criteria: echo texture, interstitial tears and neovascularity. The
      tendon was then dry needled and autologous blood was injected. Patients were
      reviewed at 4 weeks and at 10 months. VAS scores and modified Nirschl scores were
      assessed pre-procedure and post-procedure. RESULTS: There was significant
      reduction in VAS pain score between pre-procedure and 10 months post-procedure
      when it had a median (IQR) of 1.00 (1-1.75), range 0-7. The median (IQR) Nirschl
      score, which at pre-procedure was 6.00 (5-7), range 4-7, had decreased at 4 weeks
      to 4.00 (2.25-5), range 2-7, and at 10 months to 1.00 (1-1.75), range 0-7,
      revealing a significant decrease (z = 3.763, p<0.001). The hypo-echoic change in
      the flexor tendon significantly decreased between pre-procedure, when there was a
      mean (SD) of 6.45 (1.47), and at 10 months, when it was 3.85 (2.37) (p<0.001).
      Doppler ultrasound showed that neovascularity decreased between pre-procedure,
      when there was a mean (SD) of 6.10 (1.62), range 4-9, and at 10 months, when it
      was 3.60 (2.56), range 0-9 (p<0.001). DISCUSSION: The combined action of dry
      needling and autologous blood injection under ultrasound guidance appears to be
      an effective treatment for refractory medial epicondylitis as demonstrated by a
      significant decrease in VAS pain and a fall in the modified Nirschl scores.

PMID- 16990442
TI  - Sex differences in baseline neuropsychological function and concussion symptoms
      of collegiate athletes.
AB  - OBJECTIVE: To investigate sex differences in baseline neuropsychological function
      and concussion symptoms between male and female collegiate athletes. METHODS: A
      post-test only design was used to examine baseline neuropsychological test scores
      and concussion symptoms. A total of 1209 NCAA Division I collegiate athletes from
      five northeastern universities in the USA completed a baseline ImPACT test.
      ImPACT, a computerised neuropsychological test battery, was administered during
      an athlete's pre-season. RESULTS: Female athletes performed significantly better
      than male athletes on baseline verbal memory scores (p = 0.001), while male
      athletes performed significantly better than female athletes on baseline visual
      memory scores (p = 0.001). Female athletes endorsed a significant number of mild
      baseline symptoms as compared to male athletes. CONCLUSIONS: Male and female
      athletes exhibit differences on baseline neuropsychological test performance and
      concussion symptoms.

PMID- 16990443
TI  - Left ventricular dysfunction and chronic heart failure: should aqua therapy and
      swimming be allowed?

PMID- 16990444
TI  - Risk of injury in elite football played on artificial turf versus natural grass:
      a prospective two-cohort study.
AB  - OBJECTIVE: To compare injury risk in elite football played on artificial turf
      compared with natural grass. DESIGN: Prospective two-cohort study. SETTING: Male
      European elite football leagues. PARTICIPANTS: 290 players from 10 elite European
      clubs that had installed third-generation artificial turf surfaces in 2003-4, and
      202 players from the Swedish Premier League acting as a control group. MAIN
      OUTCOME MEASURE: Injury incidence. RESULTS: The incidence of injury during
      training and match play did not differ between surfaces for the teams in the
      artificial turf cohort: 2.42 v 2.94 injuries/1000 training hours and 19.60 v
      21.48 injuries/1000 match hours for artificial turf and grass respectively. The
      risk of ankle sprain was increased in matches on artificial turf compared with
      grass (4.83 v 2.66 injuries/1000 match hours; rate ratio 1.81, 95% confidence
      interval 1.00 to 3.28). No difference in injury severity was seen between
      surfaces. Compared with the control cohort who played home games on natural
      grass, teams in the artificial turf cohort had a lower injury incidence during
      match play (15.26 v 23.08 injuries/1000 match hours; rate ratio 0.66, 95%
      confidence interval 0.48 to 0.91). CONCLUSIONS: No evidence of a greater risk of
      injury was found when football was played on artificial turf compared with
      natural grass. The higher incidence of ankle sprain on artificial turf warrants
      further attention, although this result should be interpreted with caution as the
      number of ankle sprains was low.

PMID- 16990445
TI  - Enteric descending and afferent neural signaling stimulated by giant migrating
      contractions: essential contributing factors to visceral pain.
AB  - We investigated whether strong compression of an intestinal segment by giant
      migrating contractions (GMCs) initiates pseudoaffective signals from the gut,
      similar to those initiated by its distension with a balloon. The experiments were
      performed on conscious dogs by using close intra-arterial infusions of test
      substances that affect the receptors only in the infused segment. The stimulation
      of GMCs by close intra-arterial infusion of CGRP or distension of an intestinal
      segment by balloon increased the heart rate; the increase in heart rate was
      greater when the balloon distension and GMCs occurred concurrently in separate
      intestinal segments. The suppression of contractility in the distended segment
      blocked the increase in heart rate. By contrast, the stimulation of rhythmic
      phasic contractions (RPCs) or their spontaneous occurrence did not increase the
      heart rate. The occurrence of GMCs as well as intestinal distension also produced
      descending inhibition. The descending inhibition was blocked by the inhibition of
      nitric oxide synthase, but it was unaffected by the inhibition of adenylyl
      cyclase, purinergic receptors P2X and P2Y, and muscarinic receptors M(1) and
      M(2). The synaptic transmission for descending inhibition was mediated primarily
      by nicotinic receptors and activation of nitric oxide synthase. It was unaffected
      by the inhibition of tachykinin receptors NK(1), NK(2), and NK(3); serotonin
      receptors 5-HT(1A), 5-HT(2)/5-HT(1C), 5-HT(3), and 5-HT(4); and muscarinic
      receptors. Our findings show that GMCs, but not RPCs, initiate pseudoaffective
      signals from the gut. In the presence of visceral hypersensitivity or impaired
      descending inhibition, the GMCs may become a noxious stimulus.

PMID- 16990446
TI  - 5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor
      function through 5-HT4 receptors in conscious mice.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility
      and secretion. We characterized the action of the 5-HT precursor 5
      hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor
      activity in conscious mice. Fos immunoreactivity (IR), used as a marker of
      neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole
      mount preparations of the distal colon 90 min after an intraperitoneal injection
      of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase
      (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP
      (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a
      dose-related manner, with a peak response observed within the first 15 min
      postinjection. 5-HTP (0.5-10 mg/kg) dose dependently increased Fos expression in
      myenteric neurons, with a maximal response of 9.9 +/- 1.0 cells/ganglion [P <
      0.05 vs. vehicle-treated mice (2.3 +/- 0.6 cells/ganglion)]. There was a positive
      correlation between Fos expression and fecal output. Of Fos-positive ganglionic
      cells, 40 +/- 4% were also pChAT positive and 21 +/- 5% were NADPH-diaphorase
      positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos
      expression were completely prevented by pretreatment with the selective 5-HT4
      antagonist RS-39604. These results show that 5-HTP injected peripherally
      increases Fos expression in different populations of cholinergic and nitrergic
      myenteric neurons in the distal colon and stimulates propulsive colonic motor
      function through 5-HT4 receptors in conscious mice. These findings suggest an
      important role of activation of colonic myenteric neurons in the 5-HT4 receptor
      mediated colonic propulsive motor response.

PMID- 16990448
TI  - PI3K is involved in PDGF-beta receptor upregulation post-PDGF-BB treatment in
      mouse HSC.
AB  - Increased expression of PDGF-beta receptors is a landmark of hepatic stellate
      cell activation and transdifferentiation into myofibroblasts. However, the
      molecular mechanisms that regulate the fate of the receptor are lacking. Recent
      studies suggested that N-acetylcysteine enhances the extracellular degradation of
      PDGF-beta receptor by cathepsin B, thus suggesting that the absence of PDGF-beta
      receptors in quiescent cells is due to an active process of elimination and not
      to a lack of expression. In this communication we investigated further molecular
      mechanisms involved in PDGF-beta receptor elimination and reappearance after
      incubation with PDGF-BB. We showed that in culture-activated hepatic stellate
      cells there is no internal protein pool of receptor, that the protein is
      maximally phosphorylated by 5 min and completely degraded after 1 h by a
      lysosomal-dependent mechanism. Inhibition of receptor autophosphorylation by
      tyrphostin 1296 prevented its degradation, but several proteasomal inhibitors had
      no effect. We also showed that receptor reappearance is time and dose dependent,
      being more delayed in cells treated with 50 ng/ml (48 h) compared with 10 ng/ml
      (24 h).

PMID- 16990447
TI  - Two populations of Thy1-positive mesenchymal cells regulate in vitro maturation
      of hepatic progenitor cells.
AB  - We previously reported that the in vitro maturation of CD49f(+)Thy1(-)CD45(-)
      (CD49f positive) fetal hepatic progenitor cells (HPCs) is supported by Thy1
      positive mesenchymal cells derived from the fetal liver. These mesenchymal cell
      preparations contain two populations, one of a cuboidal shape and the other
      spindle shaped in morphology. In this study, we determined that the mucin-type
      transmembrane glycoprotein gp38 could distinguish cuboidal cells from spindle
      cells by immunocytochemistry. RT-PCR analysis revealed differences between
      isolated CD49f(+/-)Thy1(+)gp38(+)CD45(-) (gp38 positive) cells and CD49f(+/
      )Thy1(+)gp38(-)CD45(-) (gp38 negative) cells, whereas both cells expressed
      mesenchymal cell markers. The coculture with gp38-positive cells promoted the
      maturation of CD49f-positive HPCs, which was estimated by positivity for periodic
      acid-Schiff (PAS) staining, whereas the coculture with gp38-negative cells
      maintained CD49f-positive HPCs negative for PAS staining. The expression of
      mature hepatocyte markers, such as tyrosine aminotransferase, tryptophan-2,3
      dioxygenase, and glucose-6-phosphatase, were upregulated on HPCs by coculture
      with gp38-positive cells. Furthermore, transmission electron microscopy revealed
      the acquisition of mature hepatocyte features by HPCs cocultured with gp38
      positive cells. This effect on maturation of HPCs was inhibited by the addition
      of conditioned medium derived from gp38-negative cells. By contrast, the
      upregulation of bromodeoxyuridine incorporation by HPCs demonstrated the
      proliferative effect of coculture with gp38-negative cells. In conclusion, these
      results suggest that in vitro maturation of HPCs promoted by gp38-positive cells
      may be opposed by an inhibitory effect of gp38-negative cells, which likely
      maintain the immature, proliferative state of HPCs.

PMID- 16990449
TI  - Effects of Lactobacillus casei Shirota, Bifidobacterium breve, and oligofructose
      enriched inulin on colonic nitrogen-protein metabolism in healthy humans.
AB  - Pre- and/or probiotics can cause changes in the ecological balance of intestinal
      microbiota and hence influence microbial metabolic activities. In the present
      study, the influence of oligofructose-enriched inulin (OF-IN), Lactobacillus
      casei Shirota, and Bifidobacterium breve Yakult on the colonic fate of NH3 and p
      cresol was investigated. A randomized, placebo-controlled, crossover study was
      performed in 20 healthy volunteers to evaluate the influence of short- and long
      term administration of OF-IN, L. casei Shirota, B. breve Yakult, and the
      synbiotic L. casei Shirota + OF-IN. The lactose[15N,15N]ureide biomarker was used
      to study the colonic fate of NH3. Urine and fecal samples were analyzed for 15N
      content by combustion-isotope ratio mass spectrometery and for p-cresol content
      by gas chromatography-mass spectrometry. RT-PCR was applied to determine the
      levels of total bifidobacteria. Both short- and long-term administration of OF-IN
      resulted in significantly decreased urinary p-cresol and 15N content. The
      reduction of urinary 15N excretion after short-term OF-IN intake was accompanied
      by a significant increase in the 15N content of the fecal bacterial fraction.
      However, this effect was not observed after long-term OF-IN intake. In addition,
      RT-PCR results indicated a significant increase in total fecal bifidobacteria
      after long-term OF-IN intake. Long-term L. casei Shirota and B. breve Yakult
      intake showed a tendency to decrease urinary 15N excretion, whereas a significant
      decrease was noted in p-cresol excretion. In conclusion, dietary addition of OF
      IN, L. casei Shirota, and B. breve Yakult results in a favorable effect on
      colonic NH3 and p-cresol metabolism, which, in the case of OF-IN, was accompanied
      by an increase in total fecal bifidobacteria.

PMID- 16990450
TI  - NIH funding of the independent investigator.

PMID- 16990452
TI  - The emerging structure of vacuolar ATPases.
AB  - Bioenergetics and physiology of primary pumps have been revitalized by new
      insights into the mechanism of energizing biomembranes. Structural information is
      becoming available, and the three-dimensional structure of F-ATPase is being
      resolved. The growing understanding of the fundamental mechanism of energy
      coupling may revolutionize our view of biological processes. The F- and V-ATPases
      (vacuolar-type ATPase) exhibit a common mechanical design in which nucleotide
      binding on the catalytic sector, through a cycle of conformation changes, drives
      the transmembrane passage of protons by turning a membrane-embedded rotor. This
      motor can run in forward or reverse directions, hydrolyzing ATP as it pumps
      protons uphill or creating ATP as protons flow downhill. In contrast to F
      ATPases, whose primary function in eukaryotic cells is to form ATP at the expense
      of the proton-motive force (pmf), V-ATPases function exclusively as an ATP
      dependent proton pump. The pmf generated by V-ATPases in organelles and membranes
      of eukaryotic cells is utilized as a driving force for numerous secondary
      transport processes. V- and F-ATPases have similar structure and mechanism of
      action, and several of their subunits evolved from common ancestors. Electron
      microscopy studies of V-ATPase revealed its general structure at low resolution.
      Recently, several structures of V-ATPase subunits, solved by X-ray
      crystallography with atomic resolution, were published. This, together with
      electron microscopy low-resolution maps of the whole complex, and biochemistry
      cross-linking experiments, allows construction of a structural model for a part
      of the complex that may be used as a working hypothesis for future research.

PMID- 16990451
TI  - Selenoproteins and their impact on human health through diverse physiological
      pathways.
AB  - In the last few decades, the importance of selenium in human health has been the
      subject of numerous studies. It is believed that the physiological effects of
      selenium occur mainly through the function of selenoproteins, which incorporate
      selenium in the form of one or more selenocysteine residues. Recent advances in
      understanding the complex regulation of selenoprotein synthesis and functional
      characterization of several members of the selenoprotein family have contributed
      to an improved comprehension of the role(s) of selenium in human health and the
      great diversity of physiological pathways influenced by this trace element.

PMID- 16990453
TI  - WNK protein kinases modulate cellular Cl- flux by altering the phosphorylation
      state of the Na-K-Cl and K-Cl cotransporters.
AB  - Precise control of cellular Cl(-) transport is necessary for many fundamental
      physiological processes. For example, the intracellular concentration of Cl(-),
      fine-tuned through the coordinated action of cellular Cl(-) influx and efflux
      mechanisms, determines whether a neuron's response to GABA is excitatory or
      inhibitory. In epithelia, synchrony between apical and basolateral Cl(-) flux,
      and transcellular and paracellular Cl(-) transport, is necessary for efficient
      transepithelial Cl(-) reabsorption or secretion. In cells throughout the body,
      coordination of Cl(-) entry and exit mechanisms help defend against changes in
      cell volume. The Na-K-Cl and K-Cl cotransporters of the SLC12 gene family are
      important molecular determinants of Cl(-) entry and exit, respectively, in these
      systems. The WNK serine-threonine kinase family, members of which are mutated in
      an inherited form of human hypertension, are components of a signaling pathway
      that coordinates Cl(-) influx and efflux through SLC12 cotransporters to
      dynamically regulate intracellular Cl(-) activity.

PMID- 16990454
TI  - Molecular and physiological bases of the K+ circulation in the mammalian inner
      ear.
AB  - Endolymph, the extracellular solution in cochlea, contains 150 mM K(+) and
      exhibits a potential of approximately +80 mV relative to neighboring
      extracellular spaces. This unique situation, essential for hearing, is maintained
      by K(+) circulation from perilymph to endolymph through the cochlear lateral
      wall. Recent studies have identified ion-transport molecules involved in the K(+)
      circulation and their pathophysiological relevance.

PMID- 16990455
TI  - Remodeling the plasticity debate: the presynaptic locus revisited.
AB  - The cellular mechanisms contributing to long-term potentiation and activity
      induced formation of glutamatergic synapses have been intensely debated. Recent
      studies have sparked renewed interest in the role of presynaptic components in
      these processes. Based on the present evidence, it appears likely that long-term
      plasticity utilizes both pre- and postsynaptic expression mechanisms.

PMID- 16990456
TI  - Cortactin: the gray eminence of the cytoskeleton.
AB  - Cortactin, an actin filament-binding protein and target of multiple kinases, has
      emerged as a central element connecting signaling pathways with cytoskeleton
      restructuring. It is involved in a perplexingly diverse array of cellular
      processes, including cell motility, invasiveness, synaptogenesis, endocytosis,
      intercellular contact assembly, and host-pathogen interactions, where the common
      denominator appears to be a role in the coordination of membrane dynamics with
      cytoskeletal remodeling. Although in recent years our knowledge about cortactin
      has increased exponentially, the exact mechanisms underlying its fundamental
      roles remain to be defined.

PMID- 16990457
TI  - The mTOR pathway in the control of protein synthesis.
AB  - Signaling through mammalian target of rapamycin (mTOR) is activated by amino
      acids, insulin, and growth factors, and impaired by nutrient or energy
      deficiency. mTOR plays key roles in cell physiology. mTOR regulates numerous
      components involved in protein synthesis, including initiation and elongation
      factors, and the biogenesis of ribosomes themselves.

PMID- 16990458
TI  - Peripheral arterial disease practice guidelines and sausage.

PMID- 16990459
TI  - ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial
      Disease (lower extremity, renal, mesenteric, and abdominal aortic): a
      collaborative report from the American Associations for Vascular Surgery/Society
      for Vascular Surgery, Society for Cardiovascular Angiography and Interventions,
      Society for Vascular Medicine and Biology, Society of Interventional Radiology,
      and the ACC/AHA Task Force on Practice Guidelines (writing committee to develop
      guidelines for the management of patients with peripheral arterial disease)-
      summary of recommendations.

PMID- 16990460
TI  - The 2006 Charles T. Dotter lecture: interventional radiology--veni, vidi,
      vanished?

PMID- 16990462
TI  - Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy
      treatment for primary and secondary liver malignancies. Part 2: special topics.
AB  - Yttrium-90 microspheres are increasingly being used as a treatment modality for
      primary and secondary liver tumors. As these therapies continue to be accepted,
      it is natural that their application in more complex clinical scenarios will
      become more common. This article is meant to introduce these controversies and to
      generate interest and dialogue by the interventional oncology community. This
      discussion is based on more than 900 (90)Y radioembolization procedures performed
      over a 5-year period.

PMID- 16990461
TI  - Molecular imaging: a primer for interventionalists and imagers.
AB  - The characterization of human diseases by their underlying molecular and genomic
      aberrations has been the hallmark of molecular medicine. From this, molecular
      imaging has emerged as a potentially revolutionary discipline that aims to
      visually characterize normal and pathologic processes at the cellular and
      molecular levels within the milieu of living organisms. Molecular imaging holds
      promise to provide earlier and more precise disease diagnosis, improved disease
      characterization, and timely assessment of therapeutic response. This primer is
      intended to provide a broad overview of molecular imaging with specific focus on
      future clinical applications relevant to interventional radiology.

PMID- 16990463
TI  - Tumor ablation with photodynamic therapy: introduction to mechanism and clinical
      applications.
AB  - Photodynamic therapy (PDT) has been used to treat cancer for more than 25 years.
      Although the focus has been primarily on surface or superficial lesions, there
      has been a rapid growth in its application to the treatment of deeper parenchymal
      malignancies. The photochemical reaction consists of a photosensitizer, which,
      when irradiated by light at a specific wavelength, generates a cytotoxic oxygen
      singlet. The end result is an efficient induction of cell death, primarily
      through apoptosis, microvascular damage, and an antitumor immune response. PDT is
      currently being used in the treatment of many cancers including lung cancer, head
      and neck cancers, liver metastases, cholangiocarcinoma, and prostate cancer. The
      growing body of evidence concerning its efficacy, the increasing use of imaging
      to guide PDT, and the innate minimally invasive characteristics of PDT suggest
      that it should become an important addition to the growing array of techniques in
      interventional oncology.

PMID- 16990464
TI  - Endovenous laser ablation of the great saphenous vein with a 980-nm diode laser
      in continuous mode: early treatment failures and successful repeat treatments.
AB  - PURPOSE: To investigate the efficacy of lower-energy endovenous laser treatment
      for great saphenous vein (GSV) incompetence and treatment parameters associated
      with early treatment failure. MATERIALS AND METHODS: Sixty consecutive endovenous
      laser treatments (32 left, 28 right; 57 initial treatments, three repeat
      treatments) in 48 patients (13 men, 35 women; mean age, 55.2 +/- 12.9 years),
      with bilateral treatments in nine patients, were studied. Preprocedural clinical
      signs, etiology, anatomy, and physiologic classifications demonstrated class 2
      limbs in 11.7% of cases, class 3 limbs in 25.0%, class 4 limbs in 48.3%, and
      class 5 limbs in 15.0%. All initial and repeat treatments were performed with
      lower-energy with use of a 980-nm diode endovenous laser at 11 W in continuous
      mode. Patients wore class II compression stockings for 2 weeks and were followed
      up at 1, 3, and 6 months with clinical and duplex ultrasound examinations.
      Treatment failures were diagnosed at 3 months on the basis of GSV patency or lack
      of clinical improvement. Diameter and length of GSV treated, treatment energy
      parameters, and clinical outcomes were prospectively measured and compared
      between successful and failed treatments. RESULTS: The initial treatment success
      rate was 94.7% (54 of 57). The mean maximum diameter of successfully treated GSVs
      was 1.12 +/- 0.52 cm, and the mean maximum diameter of GSVs in which treatment
      failure occurred was 2.05 +/- 0.23 cm (P = .008). Mean total energy applied for
      successful treatments was 1,131.3 +/- 248.1 J, and mean total energy applied for
      failed treatments was 1,439.6 +/- 425.0 J (P = 0.053). Mean unit energy applied
      for successful treatments was 32.7 +/- 7.5 J/cm, and that for failed treatments
      was 32.8 +/- 4.9 J/cm (P = .986). All patients in whom treatment failed were
      successfully treated again with a mean total energy of 1,393.0 +/- 81.0 J and a
      mean unit energy of 29.4 +/- 4.9 J/cm. There were no significant differences in
      mean total energy or unit energy applied among successful, failed, and repeat
      treatments (P > .05). Mean follow-up duration was 6.8 months. CONCLUSIONS:
      Endovenous laser treatment with lower energy appears to be safe and effective.
      Larger GSV diameter is associated with early treatment failures.

PMID- 16990465
TI  - Inadvertent discontinuation of percutaneous nephrostomy catheters in adult native
      kidneys: incidence and percutaneous management.
AB  - PURPOSE: To evaluate the incidence and consequences of complete inadvertent
      percutaneous nephrostomy catheter discontinuation in native kidneys of adults. In
      addition, this study evaluated the success rate of nephrostomy tract
      recannulation. MATERIALS AND METHODS: Retrospective analysis was performed in
      adult patients who underwent percutaneous nephrostomy between January 2000 and
      December 2005. Patients' conditions were evaluated for complete inadvertent
      discontinuation of use of the nephrostomy catheters and success of subsequent
      recannulation procedures. Habitual discontinuation was defined by three catheter
      discontinuation episodes in one patient. Conditions of patients with inadvertent
      discontinuation were assessed for major complications before and after the
      recannulation, including the need for de novo nephrostomy to reestablish
      clinically needed access. The incidences of inadvertent discontinuation and
      primary assisted recannulation tract maintenance were calculated according to the
      Kaplan-Meier method. Successful versus unsuccessful recannulation procedures were
      compared for tract age, length of time the drain was out of the tract, and
      catheter diameter with use of the Mann-Whitney U test. RESULTS: A total of 283
      patients underwent 325 percutaneous nephrostomies. The inadvertent catheter
      discontinuation rates at 6, 12, 24, and 36 months were 26%, 36%, 53%, and 62%,
      respectively. For the same time intervals, the primary recannulation assisted
      tract maintenance rates were 94%, 86%, 77%, and 72%, respectively. Habitual
      discontinuation was seen in 3.2% of the total population and 19.1% of
      discontinuation cases. The technical success rates of all and first-time
      recannulations were 85% and 74%, respectively. Tract maturity was the only
      variable that was statistically significant between successful and unsuccessful
      recannulations (P < .0001). A total of 3.5% of patients required new
      nephrostomies. CONCLUSION: Despite the high incidence of inadvertent
      discontinuation of nephrostomy catheters, the major complication rate was only
      3.5%, indicating the efficacy of tract recannulation, especially in mature
      tracts.

PMID- 16990466
TI  - Radiofrequency ablation of osteoid osteoma: initial results with a bipolar
      ablation device.
AB  - PURPOSE: To report the initial results with percutaneous radiofrequency (RF)
      ablation of osteoid osteomas with a bipolar ablation device. MATERIALS AND
      METHODS: Twelve patients (seven male patients and five female patients; mean age,
      17.3 years; age range, 6-36 y) with clinically and radiologically suspected
      osteoid osteoma were treated with computed tomography-guided percutaneous bipolar
      RF ablation. The procedure was performed with the patients under general
      anesthesia. After localization of the nidus, an 11-gauge hollow drill was
      introduced into the nidus through a 9-F introducer sheath. A bipolar 18-gauge RF
      probe with a 9-mm active tip was inserted through the introducer sheath and
      connected to the RF generator. Energy application was started at 2 W and
      subsequently increased to a maximum of 5 W. The procedure was terminated if a
      resistance of 900 Omega was reached. RESULTS: Mean duration of energy deposition
      was 8.3 +/- 4.0 minutes, with a mean energy application of 1.8 +/- 2.9 kJ (range,
      0.3 - 7 kJ). In one patient, the intervention had to be repeated twice to achieve
      total pain relief. Eleven of 12 patients (92%) remained free of symptoms at a
      follow-up time of 15.1 +/- 9.5 months (range, 5 - 31 months). One patient had
      recurrence of pain 16 months after the procedure and was treated surgically. No
      complications occurred. Patients resumed normal activity within 24 hours.
      CONCLUSIONS: Percutaneous bipolar RF ablation is an efficient and safe treatment
      of osteoid osteoma. Short-term efficacy of bipolar RF ablation may rival the
      results of monopolar RF ablation. Further studies are needed to address the long
      term efficacy of this technique.

PMID- 16990467
TI  - Rhenium-188 mercaptoacetyltriglycine-filled balloon dilation in the treatment of
      recurrent urethral strictures: initial experience with five patients.
AB  - PURPOSE: To evaluate the efficacy of beta-irradiation therapy with use of a
      rhenium-188 mercaptoacetyltriglycine ((188)Re-MAG(3))-filled balloon for the
      prevention of restenosis in urethral strictures refractory to repetitive surgical
      or interventional procedures. MATERIALS AND METHODS: Five male patients with
      traumatic (n = 4) or postoperative anastomotic (n = 1) recurrent urethral
      strictures were included. One to four sessions of 20-30 Gy beta-irradiation at a
      1-mm tissue depth with (188)Re-MAG(3)-filled balloon dilation were undertaken in
      each patient. RESULTS: No procedural complications or toxicities were noted.
      During the mean follow-up period of 16.2 months, the stricture did not recur in
      two patients, whereas three patients required additional interventional
      procedures. In two of these patients, the treatment intervals between the
      required sessions were significantly prolonged. For the entire group, the mean
      treatment interval was prolonged from 2.2 months before (188)Re-MAG(3)-filled
      balloon dilation to 10.7 months after therapy. CONCLUSION: (188)Re-MAG(3)-filled
      balloon dilation shows promise in preventing or delaying stricture recurrence in
      patients with recurrent urethral strictures.

PMID- 16990468
TI  - Latent mobility of osteoporotic vertebral compression fractures.
AB  - PURPOSE: To describe the property of latent mobility in osteoporotic vertebral
      compression fractures (VCFs) and discuss its clinical significance. MATERIALS AND
      METHODS: This was a retrospective case series of 14 patients with 14 painful
      osteoporotic VCFs who were comfortably confined to the supine position overnight
      for the purpose of vertebral height restoration. There was sufficient additional
      vertebral height restoration the following morning to allow percutaneous
      vertebroplasty (PV) in some patients when this had initially been deemed unsafe
      or technically impossible. Anterior vertebral height of the index VCF was
      measured from the preoperative standing lateral, immediate cross-table supine
      lateral, and postconfinement cross-table supine lateral radiographs as well as
      the first postoperative standing lateral radiograph. Dynamic mobility was defined
      as the difference in anterior vertebral height between preoperative standing
      lateral and immediate cross-table supine lateral radiographs. Latent mobility was
      defined as difference in anterior vertebral height between immediate cross-table
      supine lateral and postconfinement cross-table supine lateral radiographs.
      Postoperative vertebral height restoration was defined as the difference in
      anterior vertebral height between preoperative and first postoperative standing
      lateral radiographs. Mean patient age was 81.0 years, and mean fracture age was
      83.6 days. RESULTS: Dynamic mobility averaged +4.7 mm (range, -2.1 to +12.6 mm; P
      = .001). Latent mobility averaged +2.7 mm (range, -1.9 to +15.5; P < .02). The
      average sum of preoperative dynamic and latent mobility (+7.4 mm; range -1.0 to
      +17.0; P < .001) was not different from final postoperative vertebral height
      restoration (P > .4). PV was successfully accomplished in all cases. CONCLUSIONS:
      Latent mobility occurs in some VCFs and contributes to vertebral height
      restoration. Recognition of latent mobility may permit vertebroplasty in some
      patients in whom the procedure had otherwise been deemed unsafe. Reports of
      vertebral height restoration following vertebral augmentation should account for
      that proportion resulting from dynamic and latent mobility.

PMID- 16990469
TI  - Patient doses from noncardiac diagnostic and therapeutic interventional
      procedures.
AB  - PURPOSE: To determine the patient doses during noncardiac diagnostic and
      therapeutic interventional procedures carried out in a dedicated angiographic
      unit. MATERIALS AND METHODS: For 1,214 interventional procedures, the technique
      type, dose-area product (DAP), cumulative dose (CD), and fluoroscopy time were
      recorded. These procedures were classified into 23 categories (10 diagnostic and
      13 therapeutic) that included nine to 259 patients each. For each category,
      descriptive statistical analysis was used to determine the characteristics of
      DAP, CD, and fluoroscopy time distributions. The statistical significance of the
      differences observed between categories in terms of DAP was assessed. RESULTS:
      For the 23 categories studied, the median DAP values ranged from 0.2 to 176.8
      Gycm(2). In comparison with the literature, the mean and median DAP values in
      this study were within reported ranges for eight categories, greater for three,
      and less for six, whereas for the remaining six categories no relevant data were
      found in the literature. CONCLUSIONS: Overall, the results of this survey
      indicate that the techniques used by the interventionalists, the operation skills
      of radiation technologists, and the performance of the x-ray unit present no
      obvious deficiencies in terms of patient radiation protection. However, for those
      procedures in which lower DAP values were found in the literature, it should be
      further investigated whether patient doses could be reduced without degradation
      of the diagnostic and therapeutic outcomes.

PMID- 16990470
TI  - Endoluminal cryotherapy to prevent recanalization after endovascular occlusion
      with platinum coils.
AB  - PURPOSE: Endovascular embolization with platinum coils is sometimes followed by
      recanalization. The present study was undertaken to assess whether cryoablation
      of the endothelial lining could prevent recanalization after coil occlusion.
      MATERIALS AND METHODS: Recanalization rates of canine maxillary and vertebral
      arteries (n = 20) occluded with platinum coils with or without previous
      cryoablation (with temperatures of -40 degrees C to -45 degrees C for 90 seconds)
      were analyzed by angiography immediately and at 1 and 3 months in five animals.
      Pathologic recanalization and fibrosis was assessed at 3 months with use of a
      qualitative scoring system. Findings were compared with Mann-Whitney tests.
      RESULTS: Recanalization after coil occlusion occurred in 50% and 60% of cases
      with cryoablation at 1 and 3 months, respectively, compared with 100% without
      ablation (P = .012 and P= .029). There was no significant difference in
      pathologic scores (P = .348). The brachial plexus in the vicinity of vertebral
      arteries was injured by cryotherapy in three animals in which an ipsilateral
      neurologic deficit developed. CONCLUSIONS: Cryotherapy was moderately effective
      in the prevention of recanalization after coil occlusion. Deep nerve injury was
      excessive with the protocol used in the present study.

PMID- 16990471
TI  - Prophylactic gelatin sponge tract injection to prevent bleeding after
      percutaneous renal cryoablation in a swine model.
AB  - PURPOSE: Achievement of hemostasis can be a challenge during percutaneous renal
      cryoablation (PRC). This study describes the use of a porcine model to test the
      ability of gelatin sponge injection into the tract to limit bleeding at the site
      of cryoprobe puncture. MATERIALS AND METHODS: A total of nine swine (18 kidneys)
      underwent bilateral ultrasound-guided PRC with double freeze/thaw cycle protocol
      with use of a 2.4-mm cryoprobe. The cryoablation location and protocol were
      applied identically to both kidneys in each pig; however, only one side received
      gelatin sponge injection after cryoablation through a coaxial sheath (3 mm).
      After removal of the sheath, a midline laparotomy incision was performed and
      sponges were placed around the kidneys. Blood loss was measured by calculating
      the change in weight of the sponges after 30 minutes of absorption time. Acute
      blood loss was compared between the two groups. The kidneys treated with gelatin
      sponge were removed and grossly and histologically examined to identify the
      gelatin sponge at the puncture cryolesion. RESULTS: The use of gelatin sponge
      resulted in significantly less blood loss (mean, 8.24 mg +/- 4.68) compared with
      the control kidneys (mean, 20.24 mg +/- 8.14; P = .001). Gross and
      histopathologic results confirmed that the gelatin sponge was in the cryoablation
      puncture sites. Mean diameters of cryoablation ice balls on the gelatin sponge
      and control sides were 3.9 cm +/- 0.2 and 3.8 cm +/- 0.4, respectively. The
      lesions were not significantly different between sides. CONCLUSION: Percutaneous
      tract injection of gelatin sponge appears promising as a method to decrease acute
      blood loss from PRC.

PMID- 16990472
TI  - Navigation with three-dimensional rotational radiographic data for transpedicular
      percutaneous needle introduction: feasibility and comparison with fluoroscopic
      guidance.
AB  - PURPOSE: To investigate the feasibility of navigation with three-dimensional (3D)
      rotational radiographic data for transpedicular percutaneous needle introduction
      and to compare navigation with 3D rotational radiographic data with conventional
      fluoroscopic guidance. MATERIALS AND METHODS: A navigation system was coupled to
      a 3D rotational radiographic imaging system. In a cadaver study, 60 biopsy
      needles were introduced into vertebral bodies with fluoroscopic guidance or
      navigation with 3D rotational radiographic data by two interventionalists with
      different levels of experience in percutaneous procedures. Radiation exposure,
      fluoroscopy and introduction times, and needle position were evaluated and
      compared. RESULTS: For 3D rotational radiographic navigation, the needle position
      was equivalent for both interventionalists (7 mm). For fluoroscopic guidance, the
      interventionalist with less experience in percutaneous procedures had
      significantly more pedicle cortex violations than the other interventionalist
      (eight vs one). Radiation exposure measured at the operators' hand was lower for
      3D rotational radiography-guided needle introductions. Radiation exposure
      measured at the body wall of the cadaver was equivalent between modalities (9
      mGy). CONCLUSIONS: Navigation with 3D rotational radiographic image data is
      feasible for transpedicular percutaneous needle introduction and has two
      advantages compared with fluoroscopic guidance: it poses less strict requirements
      on the expertise of the interventionalist, and it reduces radiation exposure to
      the interventionalist.

PMID- 16990473
TI  - Stent-graft treatment of thoracoabdominal aortic aneurysms after complete
      visceral debranching.
AB  - Complex thoracoabdominal aortic aneurysm repair remains a difficult problem from
      both open and endoluminal approaches. The reduced morbidity and mortality rates
      reported to be associated with aortic stent-graft procedures makes this option
      more attractive, but it is hampered by the need for adequate proximal and distal
      seal zones. While branched and fenestrated aortic stent-grafts are being refined,
      an alternative is a two-stage surgical and endoluminal approach that is
      particularly useful for aneurysms involving the aortic visceral segment. The
      present report describes stent-graft repair in two patients after complete
      visceral artery revascularization or "debranching."

PMID- 16990474
TI  - Endovascular repair of ruptured saccular aneurysms of the descending thoracic
      aorta.
AB  - Open repair of ruptured aneurysms of the descending thoracic aorta (DTA) is
      associated with early mortality rates of 20%-60% and severe morbidity rates
      exceeding 40%. The present report describes three octogenarian patients and one
      sexagenarian patient at poor surgical risk admitted with acutely ruptured
      saccular DTA aneurysms (two of four were anastomotic) unrelated to trauma or
      infection who underwent successful endovascular therapy, which involved the use
      of aortic endovascular cuffs in three cases. Mean intensive care unit and total
      hospital stay durations were 1.75 days (range, 1-4 d) and 6 days (range, 3-13 d),
      respectively. At 30 days, all patients were alive and free of repeat
      intervention, with aneurysm exclusion achieved in all cases but one, which
      featured a marginal type II endoleak. These data support endovascular therapy for
      ruptured saccular DTA aneurysms enabling short-term outcomes that otherwise would
      have been unrealistic.

PMID- 16990475
TI  - MR imaging evidence of reversal of uterine ischemia after uterine artery
      embolization for leiomyomata.

PMID- 16990476
TI  - Bronchopleural fistula treatment with use of a bronchial stent-graft occluder.
AB  - The purpose of this report is to describe our experience in the successful
      treatment of two patients with postpneumonectomy bronchopleural fistula (BPF).
      With use of computed tomography reformatting, the stent-graft occluders were
      tailored to precisely fit the fistula site and remnant bronchus stump. These were
      placed under fluoroscopic guidance via a preexisting chest tube tract in one case
      and via an open thoracostomy window site in the other. The BPFs were successfully
      occluded without complications, and the stent-graft occluders remained stable in
      position for 1 year and 6 months of follow-up, respectively.

PMID- 16990477
TI  - Endovascular intervention for infrainguinal artery disease requires additional
      evidence regarding selection of devices.

PMID- 16990478
TI  - Subdermal fluid for skin protection during superficial palliative thermal
      ablation.

PMID- 16990479
TI  - Renal vein thrombosis alters treatment times and temperatures in renal tumor
      radiofrequency ablation.

PMID- 16990480
TI  - Re: Dr. Spies' commentary on the EMMY study.

PMID- 16990481
TI  - Pre-existing inflammatory state compromises heat tolerance in rats exposed to
      heat stress.
AB  - This study investigated the roles of endotoxemia and heat-induced tissue damage
      in the pathology of heat stroke. In groups of eight, male Wistar rats were
      treated with heat exposure only (HE), or heat exposure with turpentine (T+HE),
      dexamethasone (D+HE), and turpentine and dexamethasone combined (TD+HE). The rats
      remained sedated for 2 h after receiving the respective treatments, followed by
      heat exposure until the core temperature (T(c)) was 42 degrees C for 15 min;
      control rats received turpentine (T), dexamethasone (D), and turpentine and
      dexamethasone (TD) without heat stress. Blood samples were collected before
      treatment (baseline I), after 2 h of passive rest (baseline II), at T(c) 40
      degrees C (T40), and 15 min after achieving T(c) 42 degrees C (T42). No rats died
      in the nonheat-stressed groups. Survival rate was lowest in the TD+HE rats
      (37.5%), followed by the HE (62.5%), T+HE (75%), and D+HE (100%) rats (P < 0.05).
      The duration of survival at T42 degrees C was shortest in the TD+HE rats (9.9 +/-
      6.2 min) (P < 0.01), followed by the T+HE (11.3 +/- 6.1 min) and the HE (12.2 +/-
      4 min) (P < 0.05) rats. The increase in plasma IL-6 concentrations was highest in
      the T+HE (352%) and HE (178%) rats (P < 0.05). D+HE treatment suppressed the
      increases in plasma aspartate transaminase, alanine aminotransferase, and IL-6
      and LPS concentrations during severe heat stress. Heat stroke can be triggered by
      endotoxemia or heat-induced tissue damage, and preexisting inflammation
      compromises heat tolerance, whereas blocking endotoxemia increases heat
      tolerance.

PMID- 16990482
TI  - Increased temperature, not cardiac load, activates heat shock transcription
      factor 1 and heat shock protein 72 expression in the heart.
AB  - The expression of myocardial heat shock protein 72 (HSP72) postexercise is
      initiated by the activation of heat shock transcription factor 1 (HSF1). However,
      it remains unknown which physiological stimuli govern myocardial HSF1 activation
      during exercise. These experiments tested the hypothesis that thermal stress and
      mechanical load, concomitant with simulated exercise, provide independent stimuli
      for HSF1 activation and ensuing cardiac HSP72 gene expression. To elucidate the
      independent roles of increased temperature and cardiac workload in the exercise
      mediated upregulation of left-ventricular HSP72, hearts from adult male Sprague
      Dawley rats were randomly assigned to one of five simulated exercise conditions.
      Upon reaching a surgical plane of anesthesia, each experimental heart was
      isolated and perfused using an in vitro working heart model, while independently
      varying temperatures (i.e., 37 degrees C vs. 40 degrees C) and cardiac workloads
      (i.e., low preload and afterload vs. high preload and afterload) to mimic
      exercise responses. Results indicate that hyperthermia, independent of cardiac
      workload, promoted an increase in nuclear translocation and phosphorylation of
      HSF1 compared with normothermic left ventricles. Similarly, hyperthermia,
      independent of workload, resulted in significant increases in cardiac levels of
      HSP72 mRNA. Collectively, these data suggest that HSF1 activation and HSP72 gene
      transcriptional competence during simulated exercise are linked to elevated heart
      temperature and are not a direct function of increased cardiac workload.

PMID- 16990484
TI  - The chicken embryo as a model for ductus arteriosus developmental biology:
      cracking into new territory.

PMID- 16990483
TI  - A reevaluation of the effects of stimulation of the dorsal motor nucleus of the
      vagus on gastric motility in the rat.
AB  - Our primary purpose was to characterize vagal pathways controlling gastric
      motility by microinjecting l-glutamate into the dorsal motor nucleus of the vagus
      (DMV) in the rat. An intragastric balloon was used to monitor motility. In 39 out
      of 43 experiments, microinjection of l-glutamate into different areas of the DMV
      rostral to calamus scriptorius (CS) resulted in vagally mediated excitatory
      effects on motility. We observed little evidence for inhibitory effects, even
      with intravenous atropine or with activation of gastric muscle muscarinic
      receptors by intravenous bethanechol. Inhibition of nitric oxide synthase with
      N(omega)-nitro-l-arginine methyl ester (l-NAME) HCl did not augment DMV-evoked
      excitatory effects on gastric motility. Microinjection of l-glutamate into the
      DMV caudal to CS produced vagally mediated gastric inhibition that was resistant
      to l-NAME. l-Glutamate microinjected into the medial subnucleus of the tractus
      solitarius (mNTS) also produced vagally mediated inhibition of gastric motility.
      Motility responses evoked from the DMV were always blocked by ipsilateral
      vagotomy, while responses evoked from the mNTS required bilateral vagotomy to be
      blocked. Microinjection of oxytocin into the DMV inhibited gastric motility, but
      the effect was never blocked by ipsilateral vagotomy, suggesting that the effect
      may have been due to diffusion of oxytocin to the mNTS. Microinjection of
      substance P and N-methyl-d-aspartate into the DMV also produced inhibitory
      effects attributable to excitation of nearby mNTS neurons. Our results do not
      support previous studies indicating parallel vagal excitatory and inhibitory
      pathways originating in the DMV rostral to CS. Our results do support previous
      findings of vagal inhibitory pathways originating in the DMV caudal to CS.

PMID- 16990485
TI  - The cold path to BAT.

PMID- 16990487
TI  - Sex difference in urine concentration across differing ages, sodium intake, and
      level of kidney disease.
AB  - Men are known to be at greater risk of urolithiasis and cardiovascular and renal
      diseases than women. Previous studies suggest that greater urine concentration is
      associated with acceleration of progression of chronic kidney disease (CKD),
      increased urinary albumin excretion, and delayed renal sodium excretion. The
      present review addresses possible sex-related differences in urine volume and
      osmolality (U(osm)) that could participate in this male risk predominance.
      Because of the scarcity of information, we reanalyzed 24-h urine data collected
      previously by different investigators for other purposes. In nine studies
      concerning healthy subjects (6 studies) or patients with CKD or diabetes
      mellitus, U(osm) (or another index of urine concentration based on the
      urine/plasma creatinine concentration ratio) was 21-39% higher (i.e., about a 150
      mosm/kgH2O difference) in men than in women. Urine volume was not statistically
      different. Thus, the larger osmolar load of men (related to their higher food
      intake) is excreted in a more concentrated urine with no difference in urine
      volume. This sex difference was not influenced by the level of sodium excretion
      and was still present in CKD patients. Sex differences in thirst threshold, AVP
      level, and other regulatory mediators may all contribute to the higher male
      U(osm). Because of the previously demonstrated adverse effects of vasopressin
      and/or high urine concentrating activity, the greater tendency of men to
      concentrate urine could participate in their greater susceptibility to
      urolithiasis and hypertension and to the faster progression towards end-stage
      renal failure.

PMID- 16990486
TI  - Effects of burn injury on myocardial signaling and cytokine secretion: Possible
      role of PKC.
AB  - This study examined the effects of major burn injury on the cellular distribution
      of several PKC isoforms in adult rat hearts and examined the hypothesis that PKC
      plays a regulatory role in cardiomyocyte cytokine secretion. Burn trauma was
      given over 40% total body surface area in Sprague-Dawley rats. An in vitro model
      of burn injury included addition of burn serum, 10% by volume, to primary
      cardiomyocyte cultures (collagen perfusion). In vivo burn injury produced
      redistribution of PKCdelta, PKCepsilon, and PKCalpha from the cytosol (soluble)
      to the membrane (particulate) component of the myocardium. This activation of the
      PKC isoforms was evident 2 h after burn injury and progressively increased over
      24 h postburn. Addition of burn serum to isolated myocytes produced similar PKC
      isoform redistribution from the soluble to the particulate compartment, promoted
      myocyte Ca2+ and Na+ loading, and promoted robust myocyte secretion of
      inflammatory cytokines similar to that reported after in vivo burn injury.
      Pretreating cardiomyocytes with either calphostin or PKCepsilon inhibitory
      peptide, a potent inhibitor of PKCepsilon, prevented burn serum-related
      redistribution of the PKCepsilon isoform and prevented burn serum-related
      cardiomyocyte secretion of TNF-alpha, IL-1beta, IL-6, and IL-10. These data
      suggest that the PKCepsilon isoform plays a pivotal role in myocardial
      inflammatory response to injury, altering cardiac function by modulating
      cardiomyocyte inflammatory cytokine response to injury.

PMID- 16990488
TI  - Interactive modulation of renal myogenic autoregulation by nitric oxide and
      endothelin acting through ET-B receptors.
AB  - In rats, nitric oxide modulates renal autoregulation in steady-state experiments
      and the myogenic mechanism in dynamic studies. Interactive modulation of
      autoregulation by nitric oxide and endothelin-1, predominantly involving
      endothelin B receptors, has been reported although it remains unclear whether the
      interaction is synergistic or obligatory or whether it affects the myogenic
      component of autoregulation. Nonselective inhibition of nitric oxide synthase
      (L(omega)-nitro-l-arginine methyl-ester; l-NAME) with endothelin A and B
      selective receptor antagonists BQ-123 and BQ-788, all infused into the renal
      artery, plus time series analysis were used to test the interactive actions of
      nitric oxide and endothelin on renal vascular conductance and on autoregulation.
      Nonselective endothelin receptor antagonism blunted the constrictor response to
      subsequent l-NAME but had no effect on previously established l-NAME-induced
      vasoconstriction. BQ-123 did not affect conductance and caused only minor
      reduction in myogenic autoregulatory efficiency. Responses to BQ-123 and l-NAME
      were additive and not interactive. BQ-788 and l-NAME each caused strong
      vasoconstriction alone and in the presence of the other, indicating that coupling
      between nitric oxide- and endothelin B-mediated events is not obligatory. l-NAME
      augmented myogenic autoregulation, and subsequent BQ-788 did not alter this
      response. However, BQ-788 infused alone also enhanced myogenic autoregulation but
      resulted in significant impairment of myogenic autoregulation by subsequent l
      NAME. Thus the interaction between nitric oxide and endothelin is clearly
      nonadditive and, because it is asymmetrical, cannot be explained simply by
      convergence on a common signal pathway. Instead one must postulate some degree of
      hierarchical organization and that nitric oxide acts downstream to endothelin B
      activation.

PMID- 16990489
TI  - Effect of sex hormones on renal estrogen and angiotensin type 1 receptors in
      female and male rats.
AB  - Although the mechanisms are not understood, evidence suggests that 17beta
      estradiol (E2) confers protection from cardiovascular and renal complications in
      many diseases. We have reported that E2 decreases angiotensin type 1 receptors
      (AT1Rs) in different tissues and hypothesize that E2 exerts tonic inhibition on
      AT1Rs, reducing effects of ANG II. This study determined the effects of E2 and
      dihydrotestosterone (DHT) on cortical estrogen receptors (ERs) and glomerular
      AT1R binding in rats. Animals underwent sham operation, ovariectomy (Ovx) or
      orchidectomy (Cas) and were treated (Ovx +/- E2; Cas +/- DHT) for 3 wk. Cortical
      ERalpha protein was 2.5 times greater, and ERbeta was 80% less in females vs.
      males (P < 0.01). Glomerular AT1R binding was lower in females than males [4,657
      +/- 838 vs. 7,457 +/- 467 counts per minute (cpm), P < 0.01]. Ovx reduced ERalpha
      protein by 50%, whereas E2 increased ERalpha expression after Ovx. The decrease
      in cortical ERalpha in Ovx rats was associated with a significant increase in
      AT1R binding (6,908 +/- 609 cpm), and E2 prevented this increase. There was no
      change in ERalpha or AT1R binding following Cas +/- DHT (25 mg) treatment,
      although Cas did elevate cortical ERbeta (P < 0.01). Interestingly, the high dose
      DHT (200 mg) elevated ERalpha 150% above intact levels and profoundly decreased
      AT1R binding (1,824 +/- 705 cpm, P < 0.001 vs. intact male). This indicates that
      under normal conditions, glomerular AT1R binding is significantly greater in male
      than female animals, which may be important in development of cardiovascular and
      renal disease in males. Furthermore, E2 regulates ERalpha and is inversely
      associated with glomerular AT1R binding, supporting our hypothesis that E2
      tonically suppresses AT1Rs and suggesting a potential mechanism for the
      protective effects of estrogen.

PMID- 16990490
TI  - Diversities in hepatic HIF-1, IGF-I/IGFBP-1, LDH/ICD, and their mRNA expressions
      induced by CoCl(2) in Qinghai-Tibetan plateau mammals and sea level mice.
AB  - Ochotona curzoniae and Microtus oeconomus are the native mammals living on the
      Qinghai-Tibetan-Plateau of China. The molecular mechanisms of their
      acclimatization to the Plateau-hypoxia remain unclear. Expressions of hepatic
      hypoxia-inducible factor (HIF)-1alpha, insulin-like growth factor-I (IGF-I)/IGF
      binding protein (BP)-1(IGFBP-1; including genes), and key metabolic enzymatic
      genes [lactate dehydrogenase (LDH)-A/isocitrate dehydrogenase (ICD)] are compared
      in Qinghai-Tibetan-Plateau mammals and sea-level mice after injection of CoCl(2)
      (20, 40, or 60 mg/kg) and normobaric hypoxia (16.0% O(2), 10.8% O(2), and 8.0%
      O(2)) for 6 h, tested by histochemistry, Western blot analysis, ELISA, and RT
      PCR. Major results are CoCl(2) markedly increased 1) HIF-1alpha only in mice, 2)
      hepatic and circulatory IGF-I in M. oeconomus, 3) hepatic IGFBP-1 in mice and O.
      curzoniae, and 4) LDH-A but reduced ICD mRNA in mice (CoCl(2) 20 mg/kg) but were
      unchanged in the Tibetan mammals. Normobaric hypoxia markedly 1) increased HIF
      1alpha and LDH-A mRNA in mice and M. oeconomus (8.0% O(2)) not in O. curzoniae,
      and 2) reduced ICD mRNA in mice and M. oeconomus (8.0% O(2)) not in O. curzoniae.
      Results suggest that 1) HIF-1alpha responsiveness to hypoxia is distinct in
      lowland mice and plateau mammals, reflecting a diverse tolerance of the three
      species to hypoxia; 2) CoCl(2) induces diversities in HIF-1, IGF-I/IGFBP-1
      protein or genes in mice, M. oeconomus, and O. curzoniae. In contrast, HIF-1
      mediates IGFBP-1 transcription only in mice and in M. oeconomus (subjected to
      severe hypoxia); 3) differences in IGF-I/IGFBP-1 expressions induced by CoCl(2)
      reflect significant diversities in hormone regulation and cell protection from
      damage; and 4) activation of anaerobic glycolysis and reduction of Krebs cycle
      represents strategies of lowland-animals vs. the stable metabolic homeostasis of
      plateau-acclimatized mammals.

PMID- 16990491
TI  - Molecular characterization of water-selective AQP (EbAQP4) in hagfish: insight
      into ancestral origin of AQP4.
AB  - Hagfish (Eptatretus burgeri) are agnathous and are the earliest vertebrates still
      in existence. Pavement cells adjacent to the mitochondria-rich cells show
      orthogonal arrays of particles (OAPs) in the gill of hagfish, a known
      ultrastructural morphology of aquaporin (AQP) in mammalian freeze-replica
      studies, suggesting that an AQP homolog exists in pavement cells. We therefore
      cloned water channels from hagfish gill and examined their molecular
      characteristics. The cloned AQP [E. burgeri AQP4 (EbAQP4)] encodes 288 amino
      acids, including two NPA motifs and six transmembrane regions. The deduced amino
      acid sequence of EbAQP4 showed high homology to mammalian and avian AQP4 (rat,
      44%; quail, 43%) and clustered with AQP4 subsets by the molecular phylogenetic
      tree. The osmotic water permeability of Xenopus oocytes injected with EbAQP4 cRNA
      increased eightfold compared with water-injected controls and was not reversibly
      inhibited by 0.3 mM HgCl(2). EbAQP4 mRNA expression in the gill was demonstrated
      by the RNase protection assay; antibody raised against the COOH terminus of
      EbAQP4 also detected (by Western blot analysis) a major approximately 31-kDa band
      in the gill. Immunohistochemistry and immunoelectron microscopy showed EbAQP4
      localized along the basolateral membranes of gill pavement cells. In freeze
      replica studies, OAPs were detected on the protoplasmic face of the split
      membrane comprising particles 5-6 nm long on the basolateral side of the pavement
      cells. These observations suggest that EbAQP4 is an ancestral water channel of
      mammalian AQP4 and plays a role in basolateral water transport in the gill
      pavement cells.

PMID- 16990492
TI  - Mechanism of the induction of brain c-Fos-positive neurons by lipid absorption.
AB  - Many gastrointestinal meal-related signals are transmitted to the central nervous
      system via the vagus nerve and thereby control changes in meal size. The c-Fos
      positive neuron has been used as a marker of neuronal activation after lipid
      meals to examine the contribution of a selective macronutrient on brain
      neurocircuit activity. In rats fed Intralipid, the c-Fos-positive neurons were
      highly stimulated in the nucleus of the solitary tract (NTS) and in the
      hypothalamus, including the paraventricular nucleus (PVN), arcuate nucleus of the
      hypothalamus (ARC), and ventromedial hypothalamus at 4 h lipid feeding. However,
      c-Fos-like immunoreactivity was markedly attenuated in these brain regions when
      chylomicron formation/secretion was blocked by Pluronic L-81. After lymph was
      diverted from the lymph cannulated animals, the rats had a lower number of c-Fos
      positive cells in the NTS and ARC. In contrast, the rats had higher c-Fos
      positive neurons in PVN. The present study also revealed that c-Fos-positive
      neurons induced by feeding of Intalipid were abolished by CCK type 1 receptor
      antagonist, Lorglumide. We conclude that the formation and/or secretion of
      chylomicron are critical steps for initiating neuronal activation in the brain.

PMID- 16990493
TI  - Mechanisms of renal blood flow autoregulation: dynamics and contributions.
AB  - Autoregulation of renal blood flow (RBF) is caused by the myogenic response (MR),
      tubuloglomerular feedback (TGF), and a third regulatory mechanism that is
      independent of TGF but slower than MR. The underlying cause of the third
      regulatory mechanism remains unclear; possibilities include ATP, ANG II, or a
      slow component of MR. Other mechanisms, which, however, exert their action
      through modulation of MR and TGF are pressure-dependent change of proximal
      tubular reabsorption, resetting of RBF and TGF, as well as modulating influences
      of ANG II and nitric oxide (NO). MR requires < 10 s for completion in the kidney
      and normally follows first-order kinetics without rate-sensitive components. TGF
      takes 30-60 s and shows spontaneous oscillations at 0.025-0.033 Hz. The third
      regulatory component requires 30-60 s; changes in proximal tubular reabsorption
      develop over 5 min and more slowly for up to 30 min, while RBF and TGF resetting
      stretch out over 20-60 min. Due to these kinetic differences, the relative
      contribution of the autoregulatory mechanisms determines the amount and spectrum
      of pressure fluctuations reaching glomerular and postglomerular capillaries and
      thereby potentially impinge on filtration, reabsorption, medullary perfusion, and
      hypertensive renal damage. Under resting conditions, MR contributes approximately
      50% to overall RBF autoregulation, TGF 35-50%, and the third mechanism < 15%. NO
      attenuates the strength, speed, and contribution of MR, whereas ANG II does not
      modify the balance of the autoregulatory mechanisms.

PMID- 16990494
TI  - Daily restricted feeding resets the circadian clock in the suprachiasmatic
      nucleus of CS mice.
AB  - Circadian rhythms in clock gene expressions in the suprachiasmatic nucleus (SCN)
      of CS mice and C57BL/6J mice were measured under a daily restricted feeding (RF)
      schedule in continuous darkness (DD), and entrainment of the SCN circadian
      pacemaker to RF was examined. After 2-3 wk under a light-dark cycle with free
      access to food, animals were released into DD and fed for 3 h at a fixed time of
      day for 3-4 wk. Subsequently, they returned to having free access to food for 2-3
      wk. In CS mice, wheel-running rhythms entrained to RF with a stable phase
      relationship between the activity onset and feeding time, and the rhythms started
      to free run from the feeding time after the termination of RF. mPer1, mPer2, and
      mBMAL1 mRNA rhythms in the SCN showed a fixed phase relationship with feeding
      time, indicating that the circadian pacemaker in the SCN entrained to RF. On the
      other hand, in C57BL/6J mice, wheel-running rhythms free ran under RF, and clock
      gene expression rhythms in the SCN showed a stable phase relation not to feeding
      time but to the behavioral rhythms, indicating that the circadian pacemaker in
      the SCN did not entrain. These results indicate that the SCN circadian pacemaker
      of CS mice is entrainable to RF under DD and suggest that CS mice have a
      circadian clock system that can be reset by a signal associated with feeding
      time.

PMID- 16990495
TI  - Vascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice.
AB  - There is growing evidence that sphingosine 1-phosphate (S1P) plays an important
      role in regulating the development, morphology, and function of the
      cardiovascular system. There is little data, however, regarding the relative
      contribution of endogenous S1P and its cognate receptors (referred to as S1P(1
      5)) to cardiovascular homeostasis. We used S1P(2) receptor knockout mice (S1P(2)(
      /-)) to evaluate the role of S1P(2) in heart and vascular function. There were no
      significant differences in blood pressure between wild-type and S1P(2)(-/-) mice,
      measured in awake mice. Cardiac function, evaluated in situ by using a Millar
      catheter, was also not different in S1P(2)(-/-) mice under baseline or stimulated
      conditions. In vivo analysis of vascular function by flowmetry revealed decreases
      in mesenteric and renal resistance in S1P(2)(-/-) mice, especially during
      vasoconstriction with phenylephrine. In intact aortic rings, the concentration
      force relations for both KCl and phenylephrine were right shifted in S1P(2)(-/-)
      mice, whereas the maximal isometric forces were not different. By contrast, in
      deendothelialized rings the concentration-force relations were not different but
      the maximal force was significantly greater in S1P(2)(-/-) aorta. Histologically,
      there were no apparent differences in vascular morphology. These data suggest
      that the S1P(2) receptor plays an important role in the function of the
      vasculature and is an important mediator of normal hemodynamics. This is
      mediated, at least in part, through an effect on the endothelium, but direct
      effects on vascular smooth muscle cannot be ruled out and require further
      investigation.

PMID- 16990496
TI  - Inhibition of NaCl appetite when DOCA-treated rats drink saline.
AB  - Marked increases in the consumption of concentrated NaCl solution were elicited
      in rats by daily injection of the synthetic mineralocorticoid,
      deoxycorticosterone acetate (DOCA). DOCA-treated rats drank different volumes of
      NaCl solution depending on its concentration (between 0.15 M and 0.50 M), with
      less consumed (in milliliters) the more concentrated the fluid was. In
      consequence, total Na(+) intake (in milliequivalents) was roughly similar in all
      groups. Gastric emptying of Na(+) also diminished as the concentration of the
      ingested NaCl solution increased, and the delivery of Na(+) to the small
      intestine was remarkably similar in all groups. Cumulative volume of ingested
      fluid in the stomach and small intestine was very closely related to intake (in
      milliliters) of the concentrated NaCl solutions. Systemic plasma Na(+) levels did
      not increase until after rats stopped consuming concentrated NaCl solution,
      although they were elevated at the onset of water ingestion. The situation
      appeared to be different when 0.15 M NaCl was consumed. This isotonic solution
      emptied and was absorbed relatively rapidly, and DOCA-treated rats drank larger
      amounts of it throughout a 1-h test period than when they drank concentrated NaCl
      solutions. Collectively, these findings suggest that saline consumption by DOCA
      treated rats may be inhibited by two presystemic factors, one related to the
      volume of ingested fluid (i.e., distension of the stomach and small intestine)
      and one related to its concentration (i.e., elevated osmolality of fluid in the
      small intestine and/or in adjacent visceral tissue).

PMID- 16990497
TI  - GABA(A) and GABA(B) receptors differentially modulate volume and frequency in
      ventilatory compensation in obese Zucker rats.
AB  - The aim of this study was to investigate whether GABA(A) and/or GABA(B) receptor
      mediated mechanisms contribute to the impaired ventilatory response and reduced
      maximal aerobic exercise capacity in obese Zucker rats. Ten lean and 10 obese
      Zucker rats were studied at 12 wk of age. Minute ventilation (Ve), tidal volume
      (Vt), and breathing frequency (f) during room air breathing and in response to 10
      min of hypercapnia (8% CO(2)) and 30 min of hypoxia (10% O(2)) were measured by
      the barometric method, and peak oxygen consumption (Vo(2 peak)) was measured by
      an enclosed metabolic treadmill following the randomized blinded subcutaneous
      administration of equal volumes of DMSO (vehicle), bicuculline (selective GABA(A)
      receptor antagonist, 1 mg/kg), and phaclofen (selective GABA(B) receptor
      antagonist, 1 mg/kg). Administration of bicuculline and phaclofen to lean animals
      had no effect on Ve and Vo(2 peak). Similarly, phaclofen failed to alter Ve and
      Vo(2 peak) in obese rats, although it did significantly increase f after 5-20 min
      of hypoxia. In contrast, bicuculline increased Ve and Vt relative to DMSO during
      room air breathing and after 10-30 min of hypoxic exposure in obese rats, but it
      did not increase Ve at 5 min of hypoxemia. Bicuculline increased Vo(2 peak)
      relative to DMSO in obese Zucker rats. We conclude that endogenous GABA acting on
      GABA(A) receptors can modulate Ve and Vo(2 peak) in obese but not in lean Zucker
      rats, whereas endogenous GABA acting on GABA(B) receptors modulates f during
      hypoxia (5-20 min) in obese rats in a very different manner from that when acting
      on GABA(A) receptors.

PMID- 16990498
TI  - Effects of intermittent hypoxic training on amino and fatty acid oxidative
      combustion in human permeabilized muscle fibers.
AB  - The effects of concurrent hypoxic/endurance training on mitochondrial respiration
      in permeabilized fibers in trained athletes were investigated. Eighteen endurance
      athletes were divided into two training groups: normoxic (Nor, n = 8) and hypoxic
      (H, n = 10). Three weeks (W1-W3) of endurance training (5 sessions of 1 h to 1 h
      and 30 min per week) were completed. All training sessions were performed under
      normoxic [160 Torr inspired Po(2) (Pi(O(2)))] or hypoxic conditions (
      approximately 100 Torr Pi(O(2)), approximately 3,000 m) for Nor and H group,
      respectively, at the same relative intensity. Before and after the training
      period, an incremental test to exhaustion in normoxia was performed, muscle
      biopsy samples were taken from the vastus lateralis, and mitochondrial
      respiration in permeabilized fibers was measured. Peak power output (PPO)
      increased by 7.2% and 6.6% (P < 0.05) for Nor and H, respectively, whereas
      maximal O(2) uptake (Vo(2 max)) remained unchanged: 58.1 +/- 0.8 vs. 61.0 +/- 1.2
      ml.kg(-1).min(-1) and 58.5 +/- 0.7 vs. 58.3 +/- 0.6 ml.kg(-1).min(-1) for Nor and
      H, respectively, between pretraining (W0) and posttraining (W4). Maximal ADP
      stimulated mitochondrial respiration significantly increased for glutamate +
      malate (6.27 +/- 0.37 vs. 8.51 +/- 0.33 mumol O(2).min(-1).g dry weight(-1)) and
      significantly decreased for palmitate + malate (3.88 +/- 0.23 vs. 2.77 +/- 0.08
      mumol O(2).min(-1).g dry weight(-1)) in the H group. In contrast, no significant
      differences were found for the Nor group. The findings demonstrate that 1) a 3-wk
      training period increased the PPO at sea level without any changes in Vo(2 max),
      and 2) a 3-wk hypoxic exercise training seems to alter the intrinsic properties
      of mitochondrial function, i.e., substrate preference.

PMID- 16990499
TI  - Cardiovascular variability is/is not an index of autonomic control of
      circulation.

PMID- 16990500
TI  - A "love triangle" elicited by electrochemistry: complex interactions among
      cardiac sympathetic afferent, chemo-, and baroreflexes.

PMID- 16990501
TI  - Increased mechanoreceptor stimulation explains the exaggerated exercise pressor
      reflex seen in heart failure.

PMID- 16990502
TI  - Tendon collagen synthesis at rest and after exercise in women.
AB  - In general, there is a higher incidence of musculoskeletal injuries during
      physical activity in women than in men. We hypothesized that in women rates of
      tendon collagen synthesis would be lower than in men at rest and after exercise,
      especially in the later luteal phase when estrogen and progesterone
      concentrations are higher than the early follicular phase. We studied tendon
      collagen fractional synthesis rate (FSR) in 15 young, healthy female subjects in
      either the early follicular (n = 8) or the late luteal phase (n = 7) 72 h after
      an acute bout of one-legged exercise (60 min kicking at 67% workload maximum) (72
      h) and compared the results with those previously obtained for men. Samples were
      taken from the patellar tendon in both the exercised and rested legs to determine
      collagen FSR by the incorporation of [15N]proline into tendon collagen
      hydroxyproline. There was no effect of menstrual phase on tendon collagen
      synthesis either at rest or after exercise. However, there was a significant
      difference between women and men at rest (women = 0.025 +/- 0.002%/h, men = 0.045
      +/- 0.008%/h; P < 0.05) and 72 h after exercise (women = 0.027 +/- 0.005%/h; men
      = 0.058 +/- 0.008%/h). Furthermore, rest and 72-h tendon collagen synthesis were
      not different in women, whereas in men tendon collagen synthesis remained
      significantly elevated 72 h after exercise. It is concluded that both in the
      resting state and after exercise, tendon collagen FSR is lower in women than in
      men, which may contribute to a lower rate of tissue repair after exercise.

PMID- 16990503
TI  - Excitability of human motor and visual cortex before, during, and after
      hyperventilation.
AB  - In humans, hyperventilation (HV) has various effects on systemic physiology and,
      in particular, on neuronal excitability and synaptic transmission. However, it is
      far from clear how the effects of HV are mediated at the cortical level. In this
      study we investigated the effects of HV-induced hypocapnia on primary motor (M1)
      and visual cortex (V1) excitability. We used 1) motor threshold (MT) and
      phosphene threshold (PT) and 2) stimulus-response (S-R) curves (i.e., recruitment
      curves) as measures of excitability. In the motor cortex, we additionally
      investigated 3) the intrinsic inhibitory and facilitatory neuronal circuits using
      a short-interval paired-pulse paradigm. Measurements were performed before,
      during, and after 10 min of HV (resulting in a minimum end-tidal Pco(2) of 15
      Torr). HV significantly increased motor-evoked potential (MEP) amplitudes,
      particularly at lower transcranial magnetic stimulation (TMS) intensities. Paired
      pulse stimulation indicated that HV decreases intracortical inhibition (ICI)
      without changing intracortical facilitation. The results suggestthat low Pco(2)
      levels modulate, in particular, the intrinsic neuronal circuits of ICI, which are
      largely mediated by neurons containing gamma-aminobutyric acid. Modulation of MT
      probably resulted from alterations of Na(+) channel conductances. A significant
      decrease of PT, together with higher intensity of phosphenes at low stimulus
      intensities, furthermore suggested that HV acts on the excitability of M1 and V1
      in a comparable fashion. This finding implies that HV also affects other brain
      structures besides the corticospinal motor system. The further exploration of
      these physiological mechanisms may contribute to the understanding of the various
      HV-related clinical phenomenona.

PMID- 16990504
TI  - Evaluation of two-way protein fluxes across the alveolo-capillary membrane by
      scintigraphy in rats: effect of lung inflation.
AB  - Pulmonary microvascular and alveolar epithelial permeability were evaluated in
      vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding
      was made by instilling a solution containing 99mTc-albumin in a bronchus.
      Alveolar epithelial permeability was estimated from the rate at which this tracer
      left the lungs. Microvascular permeability was simultaneously estimated measuring
      the accumulation of (111)In-transferrin in lungs. Four levels of lung distension
      (corresponding to 15, 20, 25, and 30 cmH2O end-inspiratory airway pressure) were
      studied during mechanical ventilation. Computed tomography scans showed that the
      zone of alveolar flooding underwent the same distension as the contralateral lung
      during inflation with gas. Increasing lung tissue stretch by ventilation at high
      airway pressure immediately increased microvascular, but also alveolar
      epithelial, permeability to proteins. The same end-inspiratory pressure threshold
      (between 20 and 25 cmH2O) was observed for epithelial and endothelial
      permeability changes, which corresponded to a tidal volume between 13.7 +/- 4.69
      and 22.2 +/- 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar
      space ((111)In-transferrin lung-to-heart ratio slope) was constant over 120 min,
      the rate at which 99mTc-albumin left air spaces decreased with time. This pattern
      can be explained by changes in alveolar permeability with time or by a
      compartment model including an intermediate interstitial space.

PMID- 16990505
TI  - Physiological imaging of the lung: single-photon-emission computed tomography
      (SPECT).
AB  - Emission tomography provides three-dimensional, quantitative images of the
      distribution of radiotracers used to mark physiological, metabolic, or
      pathological processes. Quantitative single photon emission computed tomography
      (SPECT) requires correction for the image-degrading effects due to photon
      attenuation and scatter. Phantom experiments have shown that radioactive
      concentrations can be assessed within some percentage of the true value when
      relevant corrections are applied. SPECT is widely spread, and radiotracers are
      available that are easy to use and comparably inexpensive. Compared with other
      methods, SPECT suffers from a lower spatial resolution, and the time required for
      image acquisition is longer than for some alternative methods. In contrast to
      some other methods, SPECT allows simultaneous imaging of more than one process,
      e.g., both regional blood flow and ventilation, for the whole lung. SPECT has
      been used to explore the influence of posture and clinical interventions on the
      spatial distribution of lung blood flow and ventilation. Lung blood flow is
      typically imaged using macroaggregates of albumin. Both radioactive gases and
      particulate aerosols labeled with radioactivity have been used for imaging of
      regional ventilation. However, all radiotracers are not equally suited for
      quantitative measurements; all have specific advantages and limitations. With
      SPECT, both blood flow and ventilation can be marked with radiotracers that
      remain fixed in the lung tissue, which allows tracer administration during
      conditions different from those at image registration. All SPECT methods have
      specific features that result from the used radiotracer, the manner in which it
      is administered, and how images are registered and analyzed.

PMID- 16990506
TI  - Fatigue and functional performance of human biceps muscle following concentric or
      eccentric contractions.
AB  - A long-lasting fatigue was measured in human biceps muscle, following 40 maximal
      isokinetic concentric or eccentric contractions of the forearm, as the response
      to single-shock stimuli every minute for 4 h. This protocol allowed new
      observations on the early time course of long-lasting fatigue. Concentric
      contractions induced a novel progressive decline to 30.2% (SE 7.8, n = 7) of
      control at 23 min with complete recovery by 120 min. Eccentric contractions lead
      initially to a smaller force reduction of similar time course followed by a
      slower decline to 40.0% (SE 5.1, n = 7) control at 120 min with recovery less
      than half complete at 4 h. A 50-Hz test stimuli overcame both fatigues,
      identifying low-frequency fatigue. EMG recordings from the biceps muscle showed
      moderate (<20%) changes during the fatigue. A visual-tracking task showed no
      decrement in performance at the time of maximal fatigue of the single-shock
      response. Because the eccentric contractions have a similar activation, a larger
      force, but much smaller metabolic usage than concentric contractions, it is
      concluded that the initial decline is related to the effects of metabolites,
      whereas the slower phase after eccentric contractions is associated with higher
      mechanical stress.

PMID- 16990507
TI  - Exercise affects the gene expression profiles of human white blood cells.
AB  - White blood cells (WBCs) express tens of thousands of genes, whose expression
      levels are modified by genetic and external factors. The purpose of the present
      study was to investigate the effects of acute exercise on gene expression
      profiles (GEPs) of WBCs and to identify suitable genes that may serve as
      surrogate markers for monitoring exercise and training load. Five male
      participants performed an exhaustive treadmill test (ET) at 80% of their maximal
      O(2) uptake (Vo(2 max)) and a moderate treadmill test (MT) at 60% Vo(2 max) for
      exactly the same time approximately 2 wk later. WBCs were isolated by the
      erythrocyte lysis method. GEPs were measured using the Affymetrix GeneChip
      technology. After scaling, normalization, and filtering, groupwise comparisons of
      gene expression intensities were performed, and several measurements were
      validated by real-time PCR. We found 450 genes upregulated and 150 downregulated
      (>1.5-fold change; ANOVA with Benjamini-Hochberg correction, P < 0.05) after ET
      that were closely associated with the gene ontology lists "response to stress"
      and "inflammatory response". Analysis of mean expression levels after MT showed
      that the extent of up- and downregulation was workload dependent. The genes for
      the stress (heat shock) proteins HSPA1A and HSPH1 and for the matrix
      metalloproteinase MMP-9 showed the most prominent increases, whereas the YES1
      oncogene (YES1) and CD160 (BY55) were most strongly reduced. Despite different
      methodological approaches used, the consistency of our results with the
      expression data of another study (Connolly PH, Caiozzo VJ, Zaldivar F, Nemet D,
      Larson J, Hung SP, Heck JD, Hatfield GW, Cooper DM. J Appl Physiol 97: 1461-1469,
      2004) suggests that expression fingerprints are useful tools for monitoring
      exercise and training loads and thereby help to avoid training-associated health
      risks.

PMID- 16990508
TI  - GABAB1 receptor subunit isoforms exert a differential influence on baseline but
      not GABAB receptor agonist-induced changes in mice.
AB  - GABA(B) receptor agonists produce hypothermia and motor incoordination. Two
      GABA(B(1)) receptor subunit isoforms exist, but because of lack of specific
      molecular or pharmacological tools, the relevance of these isoforms in
      controlling basal body temperature, locomotor activity, or in vivo responses to
      GABA(B) receptor agonists has been unknown. Here, we used mice deficient in the
      GABA(B(1a)) and GABA(B(1b)) subunit isoforms to examine the influence of these
      isoforms on both baseline motor behavior and body temperature and on the motor
      incoordinating and hypothermic responses to the GABA(B) receptor agonists l
      baclofen and gamma-hydroxybutyrate (GHB). GABA(B(1b))(-/-) mice were hyperactive
      in a novel environment and showed slower habituation than either GABA(B(1a))(-/-)
      or wild-type mice. GABA(B(1b))(-/-) mice were hyperactive throughout the
      circadian dark phase. Hypothermia in response to l-baclofen (6 and 12 mg/kg) or
      GHB (1 g/kg), baclofen-induced ataxia as determined on the fixed-speed Rotarod,
      and GHB-induced hypolocomotion were significantly, but for the most part
      similarly, attenuated in both GABA(B(1a))(-/-) and GABA(B(1b))(-/-) mice. We
      conclude that l-baclofen and GHB are nonselective for either GABA(B(1)) receptor
      isoform in terms of in vivo responses. However, GABA(B(1)) receptor isoforms have
      distinct and different roles in mediating locomotor behavioral responses to a
      novel environment. Therefore, GABA(B(1a)) and GABA(B(1b)) isoforms are
      functionally relevant molecular variants of the GABA(B(1)) receptor subunit,
      which are differentially involved in specific neurophysiological processes and
      behaviors.

PMID- 16990509
TI  - Reactive oxygen species mediate caspase activation and apoptosis induced by
      lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation.
AB  - The antioxidant alpha-lipoic acid (LA) is a naturally occurring compound that has
      been shown to possess promising anticancer activity because of its ability to
      preferentially induce apoptosis and inhibit proliferation of cancer cells
      relative to normal cells. However, the molecular mechanisms underlying the
      apoptotic effect of LA are not well understood. We report here that LA induced
      reactive oxygen species (ROS) generation and a concomitant increase in apoptosis
      of human lung epithelial cancer H460 cells. Inhibition of ROS generation by ROS
      scavengers or by overexpression of antioxidant enzymes glutathione peroxidase and
      superoxide dismutase effectively inhibited LA-induced apoptosis, indicating the
      role of ROS, especially hydroperoxide and superoxide anion, in the apoptotic
      process. Apoptosis induced by LA was found to be mediated through the
      mitochondrial death pathway, which requires caspase-9 activation. Inhibition of
      caspase activity by the pan-caspase inhibitor (z-VAD-FMK) or caspase-9-specific
      inhibitor (z-LEHD-FMK) completely inhibited the apoptotic effect of LA. Likewise,
      the mitochondrial respiratory chain inhibitor rotenone potently inhibited the
      apoptotic and ROS-inducing effects of LA, supporting the role of mitochondrial
      ROS in LA-induced cell death. LA induced down-regulation of mitochondrial Bcl-2
      protein through peroxide-dependent proteasomal degradation, and overexpression of
      the Bcl-2 protein prevented the apoptotic effect of LA. Together, our findings
      indicate a novel pro-oxidant role of LA in apoptosis induction and its regulation
      by Bcl-2, which may be exploited for the treatment of cancer and related
      apoptosis disorders.

PMID- 16990510
TI  - Reversible blockade of electron transport during ischemia protects mitochondria
      and decreases myocardial injury following reperfusion.
AB  - Cardiac mitochondria sustain damage during ischemia and reperfusion, contributing
      to cell death. The reversible blockade of electron transport during ischemia with
      amobarbital, an inhibitor at the rotenone site of complex I, protects
      mitochondria against ischemic damage. Amobarbital treatment immediately before
      ischemia was used to test the hypothesis that damage to mitochondrial respiration
      occurs mainly during ischemia and that protection of mitochondria during ischemia
      leads to decreased cardiac injury with reperfusion. Langendorff-perfused Fischer
      344 rat hearts were treated with amobarbital (2.5 mM) or vehicle for 1 min
      immediately before 25 min of global ischemia. Both groups were reperfused for 30
      min without additional treatment. Subsarcolemmal (SSM) and interfibrillar (IFM)
      populations of mitochondria were isolated after reperfusion. Ischemia and
      reperfusion decreased state 3 and increased state 4 respiration rate in both SSM
      and IFM. Amobarbital treatment protected oxidative phosphorylation measured
      following reperfusion and improved the coupling of respiration. Cytochrome c
      content measured in SSM and IFM following reperfusion decreased in untreated, but
      not in amobarbital-treated, hearts. H(2)O(2) release from SSM and IFM isolated
      from amobarbital-treated hearts during reperfusion was markedly decreased.
      Amobarbital treatment before ischemia improved recovery of contractile function
      (percentage of preischemic developed pressure: untreated 51 +/- 4%, n = 12;
      amobarbital 70 +/- 4%, n = 11, p < 0.01) and substantially reduced infarct size
      (untreated 32 +/- 2%, n = 7; amobarbital 13 +/- 2%, n = 7, p < 0.01). Thus,
      mitochondrial damage occurs mainly during ischemia rather than during
      reperfusion. Reperfusion in the setting of preserved mitochondrial respiratory
      function attenuates the mitochondrial release of reactive oxygen species,
      enhances contractile recovery, and decreases myocardial infarct size.

PMID- 16990511
TI  - Modest inflammation enhances diclofenac hepatotoxicity in rats: role of
      neutrophils and bacterial translocation.
AB  - Idiosyncratic adverse drug reactions (IADRs) represent an important human health
      problem, yet animal models for preclinical prediction of these reactions are
      lacking. Recent evidence in animals suggests that some IADRs arise from drug
      interaction with an inflammatory episode that renders the liver sensitive to
      injury. Diclofenac (DCLF) is one of those drugs for which the clinical use is
      limited by idiosyncratic liver injury. We tested the hypothesis that modest
      inflammation triggered in rats by a small dose of lipopolysaccharide (LPS)
      renders a nonhepatotoxic dose of DCLF injurious to liver. Cotreatment of rats
      with nonhepatotoxic doses of LPS and DCLF resulted in elevated serum alanine
      aminotransferase activity and liver histopathologic changes 6 h after DCLF
      administration. Neither LPS nor DCLF alone had such an effect. Gene array
      analysis of livers revealed a unique gene expression pattern in the LPS/DCLF
      cotreated group compared with groups given either agent alone. Antiserum-induced
      neutrophil (PMN) depletion in LPS/DCLF-cotreated rats protected against liver
      injury, demonstrating a role for PMNs in the pathogenesis of this LPS/DCLF
      interaction. Gut sterilization of LPS/DCLF-treated rats did not protect against
      liver injury. In contrast, gut sterilization did attenuate liver injury caused by
      a large, hepatotoxic dose of DCLF, suggesting that hepatotoxicity induced by
      large doses of DCLF is caused in part by its ability to increase intestinal
      permeability to endotoxin or other bacterial products. These results demonstrate
      that inflammation-DCLF interaction precipitates hepatotoxicity in rats and raise
      the possibility of creating animal models that predict human IADRs.

PMID- 16990512
TI  - Calcium channel blocker azelnidipine reduces glucose intolerance in diabetic mice
      via different mechanism than angiotensin receptor blocker olmesartan.
AB  - The potential combined effect and mechanism of calcium channel blockers (CCB) and
      angiotensin II type 1 receptor blockers (ARB) to improve insulin resistance were
      investigated in type 2 diabetic KK-Ay mice, focusing on their antioxidative
      action. Treatment of KK-Ay mice with a CCB, azelnidipine (3 mg/kg/day), or with
      an ARB, olmesartan (3 mg/kg/day), for 2 weeks lowered the plasma concentrations
      of glucose and insulin in the fed state, attenuated the increase in plasma
      glucose in the oral glucose tolerance test (OGTT), and increased 2-[(3)H]deoxy-d
      glucose (2-[(3)H]DG) uptake into skeletal muscle with the increase in
      translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Both
      blockers also decreased the in situ superoxide production in skeletal muscle. The
      decrease in plasma concentrations of glucose and insulin in the fed state and
      superoxide production in skeletal muscle, as well as GLUT4 translocation to the
      plasma membrane, after azelnidipine administration was not significantly affected
      by coadministration of an antioxidant, 2,2,6,6-tetramethyl-1-piperidinyloxy
      (tempol). However, those changes caused by olmesartan were further improved by
      tempol. Moreover, olmesartan enhanced the insulin-induced tyrosine
      phosphorylation of insulin receptor substrate-1 induced in skeletal muscle,
      whereas azelnidipine did not change it. Coadministration of azelnidipine and
      olmesartan further decreased the plasma concentrations of glucose and insulin,
      improved OGTT, and increased 2-[(3)H]DG uptake in skeletal muscle. These results
      suggest that azelnidipine improved glucose intolerance mainly through inhibition
      of oxidative stress and enhanced the inhibitory effects of olmesartan on glucose
      intolerance, as well as the clinical possibility that the combination of CCB and
      ARB could be more effective than monotherapy in the treatment of insulin
      resistance.

PMID- 16990513
TI  - Odorant receptor-derived cAMP signals direct axonal targeting.
AB  - In mammals, odorant receptors (ORs) direct the axons of olfactory sensory neurons
      (OSNs) toward targets in the olfactory bulb. We show that cyclic adenosine
      monophosphate (cAMP) signals that regulate the expression of axon guidance
      molecules are essential for the OR-instructed axonal projection. Genetic
      manipulations of ORs, stimulatory G protein, cAMP-dependent protein kinase, and
      cAMP response element-binding protein shifted the axonal projection sites along
      the anteriorposterior axis in the olfactory bulb. Thus, it is the OR-derived cAMP
      signals, rather than direct action of OR molecules, that determine the target
      destinations of OSNs.

PMID- 16990514
TI  - Control of peripheral nerve myelination by the beta-secretase BACE1.
AB  - Although BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1) is
      essential for the generation of amyloid-b peptide in Alzheimer's disease, its
      physiological function is unclear. We found that very high levels of BACE1 were
      expressed at time points when peripheral nerves become myelinated. Deficiency of
      BACE1 resulted in the accumulation of unprocessed neuregulin 1 (NRG1), an
      axonally expressed factor required for glial cell development and myelination.
      BACE1-/- mice displayed hypomyelination of peripheral nerves and aberrant axonal
      segregation of small-diameter afferent fibers, very similar to that seen in mice
      with mutations in type III NRG1 or Schwann cell-specific ErbB2 knockouts. Thus,
      BACE1 is required for myelination and correct bundling of axons by Schwann cells,
      probably through processing of type III NRG1.

PMID- 16990516
TI  - Wetland sedimentation from hurricanes Katrina and Rita.
AB  - More than 131 x 10(6) metric tons (MT) of inorganic sediments accumulated in
      coastal wetlands when Hurricanes Katrina and Rita crossed the Louisiana coast in
      2005, plus another 281 x 10(6) MT when accumulation was prorated for open water
      area. The annualized combined amount of inorganic sediments per hurricane equals
      (i) 12% of the Mississippi River's suspended load, (ii) 5.5 times the inorganic
      load delivered by overbank flooding before flood protection levees were
      constructed, and (iii) 227 times the amount introduced by a river diversion built
      for wetland restoration. The accumulation from hurricanes is sufficient to
      account for all the inorganic sediments in healthy saltmarsh wetlands.

PMID- 16990517
TI  - The Women's Health Initiative.

PMID- 16990515
TI  - Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels.
AB  - To resolve the controversy about messengers regulating KCNQ ion channels during
      phospholipase C-mediated suppression of current, we designed translocatable
      enzymes that quickly alter the phosphoinositide composition of the plasma
      membrane after application of a chemical cue. The KCNQ current falls rapidly to
      zero when phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2 or PI(4,5)P2] is
      depleted without changing Ca2+, diacylglycerol, or inositol 1,4,5-trisphosphate.
      Current rises by 30% when PI(4,5)P2 is overproduced and does not change when
      phosphatidylinositol 3,4,5-trisphosphate is raised. Hence, the depletion of
      PI(4,5)P2 suffices to suppress current fully, and other second messengers are not
      needed. Our approach is ideally suited to study biological signaling networks
      involving membrane phosphoinositides.

PMID- 16990518
TI  - Gender issues. Universities urged to improve hiring and advancement of women.

PMID- 16990519
TI  - Geology. Katrina study stirs debate on coastal restoration.

PMID- 16990520
TI  - Genetically modified crops. Tracing the transatlantic spread of GM rice.

PMID- 16990521
TI  - Bioethics. Researchers attack newspaper probe of trials.

PMID- 16990522
TI  - Clinical trials. A shot of bone marrow can help the heart.

PMID- 16990523
TI  - Paleoanthropology. Lucy's 'child' offers rare glimpse of an ancient toddler.

PMID- 16990524
TI  - Ocean science. Creatures great and small are stirring the ocean.

PMID- 16990525
TI  - Archaeology. Mad about pyramids.

PMID- 16990526
TI  - Scientific workforce. Frustrations mount over China's high-priced hunt for trophy
      professors.

PMID- 16990527
TI  - Scientific workforce. Many overseas Chinese researchers find coming home a
      revelation.

PMID- 16990528
TI  - Ornithology. The pink death: die-offs of the lesser flamingo raise concern.

PMID- 16990529
TI  - Mantle dynamics. Rising plumes in Earth's mantle: phantom or real?

PMID- 16990530
TI  - 2006 Visualization Challenge.

PMID- 16990531
TI  - 2006 Visualization Challenge winners.
AB  - Science and the National Science Foundation announce the winners and honorable
      mentions in the categories of photography, illustration, informational graphics,
      noninteractive multimedia, and interactive multimedia in this year's Science and
      Engineering Visualization Challenge.

PMID- 16990532
TI  - Debating the cause of a neurological disorder.

PMID- 16990533
TI  - Top-down vs. bottom-up effects in kelp forests.

PMID- 16990534
TI  - Comment on "A keystone mutualism drives pattern in a power function".
AB  - Vandermeer and Perfecto (Reports, 17 February 2006, p. 1000) reported a general
      power law pattern in the distribution of a common agricultural pest. However,
      there is an exact analytical solution for the expected cluster distribution under
      the proposed null model of density-independent growth in a patchy landscape.
      Reanalysis of the data shows that the system is not in a critical state but
      confirms the importance of a mutualism.

PMID- 16990535
TI  - Comment on "A keystone mutualism drives pattern in a power function".
AB  - Vandermeer and Perfecto (Reports, 17 February 2006, p. 1000) maintain that a
      mutualist ant disrupts the power law distribution of scale insect abundances.
      However, reanalysis of the data reveals that ants cause an increase in the range
      of the power law and modify its exponent. We present a tentative, but more
      realistic, model that is suitable for quantitative predictions.

PMID- 16990536
TI  - Ecology. Adding biofuels to the invasive species fire?

PMID- 16990537
TI  - Planetary science: Meteorites and their parent asteroids.

PMID- 16990538
TI  - Neuroscience. Adam finds an exciting mate.

PMID- 16990539
TI  - Molecular biology. Versatility of self-cleaving ribozymes.

PMID- 16990540
TI  - Geophysics. Do earthquakes rupture piece by piece or all together?

PMID- 16990541
TI  - Molecular biology. Little molecules with big goals.

PMID- 16990542
TI  - SUMO1 haploinsufficiency leads to cleft lip and palate.
AB  - The posttranslational modification sumoylation can have multiple effects on its
      substrate proteins. We studied a patient with isolated cleft lip and palate and a
      balanced chromosomal translocation that disrupts the SUMO1 (small ubiquitin
      related modifier) gene, resulting in haploinsufficiency. In mouse, we found that
      Sumo1 is expressed in the developing lip and palate and that a Sumo1 hypomorphic
      allele manifests an incompletely penetrant orofacial clefting phenotype. Products
      of several genes implicated in clefting are sumoylated, and the Sumo1 hypomorphic
      allele interacts genetically with a loss-of-function allele for one of these
      loci. Thus, sumoylation defines a network of genes important for palatogenesis.

PMID- 16990543
TI  - Structural basis of glmS ribozyme activation by glucosamine-6-phosphate.
AB  - The glmS ribozyme is the only natural catalytic RNA known to require a small
      molecule activator for catalysis. This catalytic RNA functions as a riboswitch,
      with activator-dependent RNA cleavage regulating glmS messenger RNA expression.
      We report crystal structures of the glmS ribozyme in precleavage states that are
      unliganded or bound to the competitive inhibitor glucose-6-phosphate and in the
      postcleavage state. All structures superimpose closely, revealing a remarkably
      rigid RNA that contains a preformed active and coenzyme-binding site. Unlike
      other riboswitches, the glmS ribozyme binds its activator in an open, solvent
      accessible pocket. Our structures suggest that the amine group of the glmS
      ribozyme-bound coenzyme performs general acid-base and electrostatic catalysis.

PMID- 16990544
TI  - Self-healing pulse-like shear ruptures in the laboratory.
AB  - Models predict that dynamic shear ruptures during earthquake faulting occur as
      either sliding cracks, where a large section of the interface slides behind a
      fast-moving rupture front, or self-healing slip pulses, where the fault relocks
      shortly behind the rupture front. We report experimental visualizations of crack
      like, pulse-like, and mixed rupture modes propagating along frictionally held,
      "incoherent" interfaces separating identical solids, and we describe the
      conditions under which those modes develop. A combination of simultaneously
      performed measurements via dynamic photoelasticity and laser interferometry
      reveals the rupture mode type, the exact point of rupture initiation, the sliding
      velocity history, and the rupture propagation speed.

PMID- 16990545
TI  - Observations of biologically generated turbulence in a coastal inlet.
AB  - Measurements in a coastal inlet revealed turbulence that was three to four orders
      of magnitude larger during the dusk ascent of a dense acoustic-scattering layer
      of krill than during the day, elevating daily-averaged mixing in the inlet by a
      factor of 100. Because vertically migrating layers of swimming organisms are
      found in much of the ocean, biologically generated turbulence may affect (i) the
      transport of inorganic nutrients to the often nutrient-depleted surface layer
      from underlying nutrient-rich stratified waters to affect biological productivity
      and (ii) the exchange of atmospheric gases such as CO2 with the stratified ocean
      interior, which has no direct communication with the atmosphere.

PMID- 16990546
TI  - Waking experience affects sleep need in Drosophila.
AB  - Sleep is a vital, evolutionarily conserved phenomenon, whose function is unclear.
      Although mounting evidence supports a role for sleep in the consolidation of
      memories, until now, a molecular connection between sleep, plasticity, and memory
      formation has been difficult to demonstrate. We establish Drosophila as a model
      to investigate this relation and demonstrate that the intensity and/or complexity
      of prior social experience stably modifies sleep need and architecture.
      Furthermore, this experience-dependent plasticity in sleep need is subserved by
      the dopaminergic and adenosine 3',5'-monophosphate signaling pathways and a
      particular subset of 17 long-term memory genes.

PMID- 16990547
TI  - Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and
      host.
AB  - Protein aggregation is an established pathogenic mechanism in Alzheimer's
      disease, but little is known about the initiation of this process in vivo.
      Intracerebral injection of dilute, amyloid-beta (Abeta)-containing brain extracts
      from humans with Alzheimer's disease or beta-amyloid precursor protein (APP)
      transgenic mice induced cerebral beta-amyloidosis and associated pathology in APP
      transgenic mice in a time- and concentration-dependent manner. The seeding
      activity of brain extracts was reduced or abolished by Abeta immunodepletion,
      protein denaturation, or by Abeta immunization of the host. The phenotype of the
      exogenously induced amyloidosis depended on both the host and the source of the
      agent, suggesting the existence of polymorphic Abeta strains with varying
      biological activities reminiscent of prion strains.

PMID- 16990548
TI  - Therapy-induced acute recruitment of circulating endothelial progenitor cells to
      tumors.
AB  - The contribution of bone marrow-derived circulating endothelial progenitor cells
      (CEPs) to tumor angiogenesis has been controversial, primarily because of their
      low numbers in blood vessels of untreated tumors. We show that treatment of tumor
      bearing mice with vascular disrupting agents (VDAs) leads to an acute
      mobilization of CEPs, which home to the viable tumor rim that characteristically
      remains after such therapy. Disruption of this CEP spike by antiangiogenic drugs
      or by genetic manipulation resulted in marked reductions in tumor rim size and
      blood flow as well as enhanced VDA antitumor activity. These findings also
      provide a mechanistic rationale for the enhanced efficacy of VDAs when combined
      with antiangiogenic drugs.

PMID- 16990549
TI  - A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3
      gene.
AB  - Ribozymes are thought to have played a pivotal role in the early evolution of
      life, but relatively few have been identified in modern organisms. We performed
      an in vitro selection aimed at isolating self-cleaving RNAs from the human
      genome. The selection yielded several ribozymes, one of which is a conserved
      mammalian sequence that resides in an intron of the CPEB3 gene, which belongs to
      a family of genes regulating messenger RNA polyadenylation. The CPEB3 ribozyme is
      structurally and biochemically related to the human hepatitis delta virus (HDV)
      ribozymes. The occurrence of this ribozyme exclusively in mammals suggests that
      it may have evolved as recently as 200 million years ago. We postulate that HDV
      arose from the human transcriptome.

PMID- 16990550
TI  - Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic
      transmission.
AB  - Abnormally synchronized synaptic transmission in the brain causes epilepsy. Most
      inherited forms of epilepsy result from mutations in ion channels. However, one
      form of epilepsy, autosomal dominant partial epilepsy with auditory features
      (ADPEAF), is characterized by mutations in a secreted neuronal protein, LGI1. We
      show that ADAM22, a transmembrane protein that when mutated itself causes
      seizure, serves as a receptor for LGI1. LGI1 enhances AMPA receptor-mediated
      synaptic transmission in hippocampal slices. The mutated form of LGI1 fails to
      bind to ADAM22. ADAM22 is anchored to the postsynaptic density by cytoskeletal
      scaffolds containing stargazin. These studies in rat brain indicate possible
      avenues for understanding human epilepsy.

PMID- 16990551
TI  - Melagatran reduces advanced atherosclerotic lesion size and may promote plaque
      stability in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: Inflammatory mechanisms are involved in atherosclerotic plaque rupture
      and subsequent thrombin formation. Thrombin not only plays a central role in
      thrombus formation and platelet activation, but also in the induction of
      inflammatory processes. We assessed the hypothesis that melagatran, a direct
      thrombin inhibitor, attenuates plaque progression and promotes stability of
      advanced atherosclerotic lesions. METHODS AND RESULTS: Melagatran (500
      micromol/kg/d) or control diet was administered to apolipoprotein E-deficient
      mice (n=54) with advanced atherosclerotic lesions. Treatment reduced lesion
      progression in brachiocephalic arteries (P<0.005). Morphometric analysis
      confirmed that thrombin inhibition promoted plaque stability and resulted in
      thicker fibrous caps (28.4+/-14.2 microm versus 20.8+/-12.0 microm; P<0.05),
      increased media thickness (29.3+/-9.6 microm versus 24.4+/-6.7 microm; P<0.05),
      and smaller necrotic cores (73,537+/-41,301 microm2 versus 126,819+/-51,730
      microm2; P<0.0005). Electro mobility shift assays revealed reduced binding
      activity of nuclear factor kappaB (P<0.05) and activator protein-1 (P<0.05) in
      aortas of treated mice. Furthermore, immunohistochemistry demonstrated reduced
      staining for matrix metalloproteinase (MMP)-9 (P<0.05). Melagatran had no
      significant effect on early lesion formation in C57BL/6J mice. CONCLUSIONS: The
      direct thrombin inhibitor melagatran reduces lesion size and may promote plaque
      stability in apolipoprotein E-deficient mice, possibly through reduced activation
      of proinflammatory transcription factors and reduced synthesis of MMP-9.

PMID- 16990552
TI  - The role of human antigen R, an RNA-binding protein, in mediating the
      stabilization of toll-like receptor 4 mRNA induced by endotoxin: a novel
      mechanism involved in vascular inflammation.
AB  - OBJECTIVE: Lipopolysaccharide (LPS) interacts with toll-like receptor 4 (TLR4)
      and induces proliferation of vascular smooth muscle cells (VSMCs) which plays a
      causal role in atherogenesis. The role of TLR4 expression and regulation in LPS
      stimulated VSMCs remains unclear. TLR4 mRNAs often contain AU-rich elements
      (AREs) in their 3' untranslated regions (3'UTR) which have a high affinity for
      RNA-binding proteins. It is not know whether the RNA-binding protein, human
      antigen R (HuR), regulates TLR4 expression in human aortic smooth muscle cells
      (HASMCs). METHODS AND RESULTS: Stimulation of HASMCs with LPS significantly
      increased the cytosolic HuR level in vitro. Immunoprecipitation and RT-PCR
      demonstrated that LPS markedly increased the interaction of HuR and 3'UTR of TLR4
      mRNA. The reporter plasmid, which contains the 3'UTR of TLR4 mRNA, significantly
      increased luciferase reporter gene expression in LPS-induced HASMCs. These data
      suggest that the 3'UTR of TLR4 mRNA confers LPS responsiveness and that HuR
      modulates 3'UTR-mediated gene expression. Knock-down of HuR inhibited LPS-induced
      TLR4 mRNA stability in HASMCs and luciferase reporter gene expression in CMV
      Luciferase-TLR4 3'UTR-transfected HASMCs. In addition, inhibition of NADPH
      oxidase activity by diphenylene iodonium, knock-down of Rac1 gene expression by
      siRNA, and decrease of p38 MAPK activity by SB203580 significantly decreased the
      cytosolic HuR level, which mediates TLR4 mRNA stability. CONCLUSIONS: Activation
      of NADPH oxidase and the MAPK-signaling pathway contribute to HuR-mediated
      stabilization of TLR4 mRNA induced by LPS in HASMCs. In the balloon injured
      rabbit aorta model, systemic inflammation induced by LPS caused intimal
      hyperplasia and increased TLR4 and HuR expression.

PMID- 16990553
TI  - Antioxidants relieve phosphatase inhibition and reduce PDGF signaling in cultured
      VSMCs and in restenosis.
AB  - OBJECTIVE: Growth factor- and reactive oxygen species (ROS)-induced activation of
      VSMCs is involved in vascular disease. This study investigates whether inhibitory
      oxidation of protein tyrosine phosphatases (PTPs) contributes to signaling in
      VSMCs in vitro and in vivo, and analyzes whether ROS- and growth factor-dependent
      vascular smooth muscle cell (VSMC) signaling is blunted by antioxidants that are
      able to activate oxidized PTPs. METHODS AND RESULTS: Signaling induced by H2O2
      and platelet-derived growth factor (PDGF) was analyzed in VSMCs with or without
      the antioxidants N-acetyl-cysteine (NAC) and tempol. Effects of antioxidants on
      PDGF-stimulated chemotaxis and proliferation were determined. In vivo effects of
      antioxidants were analyzed in the rat carotid balloon-injury model, by analyzing
      neointima formation, cell proliferation, PDGF beta-receptor status, and PTP
      expression and activity. NAC treatment prevented H2O2-induced PTP inhibition, and
      reduced H2O2- and ligand-induced PDGF beta-receptor phosphorylation, PDGF-induced
      proliferation, and chemotaxis of VSMCs. Antioxidants inhibited neointima
      formation and reduced PDGF receptor phosphorylation in the neointima and also
      increased PTP activity. CONCLUSIONS: PTP-inhibition was identified as an
      intrinsic component of H2O2- and PDGF-induced signaling in cultured VSMCs. The
      reduction in PDGF beta-receptor phosphorylation in vivo, and the increase in PTP
      activity, by antioxidants indicate activation of oxidized PTPs as a previously
      unrecognized mechanism for the antirestenotic effects of antioxidants. The
      findings thus suggest, in general terms, reactivation of oxidized PTPs as a novel
      antirestenotic strategy.

PMID- 16990554
TI  - Procoagulant microparticles: disrupting the vascular homeostasis equation?
AB  - Apoptosis and vascular cell activation are main contributors to the release of
      procoagulant microparticles (MPs), deleterious partners in atherothrombosis.
      Elevated levels of circulating platelet, monocyte, or endothelial-derived MPs are
      associated with most of the cardiovascular risk factors and appear indicative of
      poor clinical outcome. In addition to being a valuable hallmark of vascular cell
      damage, MPs are at the crossroad of atherothrombosis processes by exerting direct
      effects on vascular or blood cells. Under pathological circumstances, circulating
      MPs would support cellular cross-talk leading to vascular inflammation and tissue
      remodeling, endothelial dysfunction, leukocyte adhesion, and stimulation. Exposed
      membrane phosphatidylserine and functional tissue factor (TF) are 2 procoagulant
      entities conveyed by circulating MPs. At sites of vascular injury, P-selectin
      exposure by activated endothelial cells or platelets leads to the rapid
      recruitment of MPs bearing the P-selectin glycoprotein ligand-1 and blood-borne
      TF, thereby triggering coagulation. Within the atherosclerotic plaque,
      sequestered MPs constitute the main reservoir of TF activity, promoting
      coagulation after plaque erosion or rupture. Lesion-bound MPs, eventually
      harboring proteolytic and angiogenic effectors are additional actors in plaque
      vulnerability. Pharmacological strategies aimed at modulating the release of
      procoagulant MPs appear a promising therapeutic approach of both thrombotic
      processes and bleeding disorders.

PMID- 16990555
TI  - Loss of the lysophosphatidylcholine effector, G2A, ameliorates aortic
      atherosclerosis in low-density lipoprotein receptor knockout mice.
AB  - OBJECTIVE: Lysophosphatidylcholine is a major product of low-density lipoprotein
      (LDL) oxidation and secretory phospholipase A2-mediated lipid hydrolysis within
      atherosclerotic lesions. The G2A receptor mediates chemotaxis of cultured
      macrophages and T cells to lysophosphatidylcholine, supporting a pro-atherogenic
      role for this receptor in vivo. We investigated the ability of G2A to modulate
      atherosclerosis in mice. METHODS AND RESULTS: We measured atherosclerosis in
      G2A+/+ and G2A-/- LDL receptor knockout (LDLR-/-) mice. Consistent with a
      previous study, early lesion size at the aortic sinus was unaffected by G2A
      deficiency. However, G2A deficiency attenuated lesion progression at this site
      (42% to 44% reduction in average lesion area) and led to robust suppression of
      atherosclerosis throughout the aorta after short and extended periods of diet
      intervention (reduction in aortic lesion coverage: 62% to 73% at 9 weeks, 75% to
      84% at 20 weeks). In G2A-/- LDLR-/- mice, intimal macrophage accumulation at
      lesion-prone sites of the aorta was significantly reduced in the absence of any
      detectable effect on T cell recruitment. Examination of lipoprotein profiles
      revealed elevated levels of circulating high-density lipoprotein (HDL)
      cholesterol in G2A-/- LDLR-/- mice compared with their G2A+/+ LDLR-/-
      counterparts after extended periods of diet intervention (54% increase in mean
      HDL cholesterol concentration). CONCLUSIONS: G2A provides a pro-atherogenic
      stimulus in vivo consistent with its chemotactic action but to which a pleiotropy
      of effects, including modulation of lipoprotein metabolism, may also contribute.

PMID- 16990556
TI  - Hereditary postprandial hypertriglyceridemic rabbit exhibits insulin resistance
      and central obesity: a novel model of metabolic syndrome.
AB  - OBJECTIVE: We have established a hereditary postprandial hypertriglyceridemic
      (PHT) rabbit. The present study was designed to define whether this rabbit model
      represents both insulin resistance and central obesity. METHODS AND RESULTS: Body
      weight, abdominal circumference, visceral fat weight, and glucose tolerance were
      compared between PHT and Japanese white (JW) rabbit. Plasma levels of
      triglycerides (TG), total cholesterol (TC), glucose, and insulin were measured
      before and after feeding. Abdominal circumference of PHT rabbit was larger than
      that of JW rabbit, with no difference in body mass index. Visceral fat
      accumulation was noted as obvious in mesenterium, retroperitoneal space, and
      epididymal area. Plasma TG and TC levels were high preprandially and markedly
      increased postprandially in PHT rabbit compared with JW rabbit. Although plasma
      glucose levels were comparable in both groups, plasma insulin levels were
      elevated in PHT rabbit. Glucose tolerance tests indicated that plasma insulin
      levels in PHT rabbit were consistently higher than in JW rabbit. A positive
      correlation was observed between plasma insulin levels and visceral fat weight in
      PHT rabbit. CONCLUSIONS: PHT rabbit shows insulin resistance along with central
      obesity. PHT rabbit will serve as a model for elucidating genetic predisposition
      and pathophysiology in metabolic syndrome.

PMID- 16990557
TI  - cNGR: a novel homing sequence for CD13/APN targeted molecular imaging of murine
      cardiac angiogenesis in vivo.
AB  - OBJECTIVE: Previously, the peptide sequence cNGR has been shown to home
      specifically to CD13/APN (aminopeptidase N) on tumor endothelium. Here, we
      investigated the feasibility of selective imaging of cardiac angiogenesis using
      the cNGR-CD13/APN system. METHODS AND RESULTS: CD13/APN induction and cNGR homing
      were studied in the murine myocardial infarction (MI) model. By real-time
      polymerase chain reaction (PCR) at 7 days after MI, CD13/APN expression was 10-
      to 20-fold higher in the angiogenic infarct border zone and the MI area than in
      non-MI areas. In vivo fluorescence microscopy confirmed specific homing of
      fluorophore-tagged cNGR to the border zone and MI territory at 4 and 7 days after
      MI with a local advantage of 2.3, but not at 1 or 14 days after MI. Tissue
      residence half-life was 9.1+/-0.3 hours, whereas the half-life in plasma was
      15.4+/-3.4 minutes. Pulse chase experiments confirmed reversible binding of cNGR
      in the infarct area. Fluorescent labeled cNGR conjugates or antibodies were
      injected in vivo, and their distribution was studied ex vivo by 2-photon laser
      scanning microscopy (TPLSM). cNGR co-localized exclusively with CD13/APN and the
      endothelial marker CD31 on vessels. CONCLUSIONS: In cardiac angiogenesis
      endothelial CD13/APN is upregulated. It can be targeted specifically with cNGR
      conjugates. In the heart cNGR binds its endothelial target only in angiogenic
      areas.

PMID- 16990558
TI  - Critical role of inducible costimulator signaling in the development of
      arteriosclerosis.
AB  - OBJECTIVE: Proliferation and migration of smooth muscle cells (SMCs) and
      migration and accumulation of monocytes and T cells are landmark events in the
      development of arteriosclerosis. SMC proliferation in the intima induces
      interruption of blood flow and results in ischemia and graft rejection. Inducible
      costimulator (ICOS) is a major costimulator of T cell activation. However, the
      effect of costimulatory molecules on the formation of neointimal hyperplasia has
      not been fully elucidated. We examined the role of the ICOS pathway in SMC
      proliferation. METHODS AND RESULTS: ICOS ligand (ICOSL) was detected in SMCs
      stimulated by interleukin (IL)-1beta, and coculture of stimulated SMCs and
      activated T cells induced SMC proliferation. Inhibition of the ICOS pathway
      resulted in inhibition of SMC proliferation. In models of transplantation and
      vascular injury, ICOSL was induced in SMCs in the neointima. Expression of IL
      1beta, a key inducer of ICOSL expression, was significantly reduced in mice
      treated with anti-ICOS antibody or soluble form of ICOS (ICOSIg) and in ICOS
      deficient mice. Inhibition of the ICOS pathway significantly suppressed
      neointimal thickening. CONCLUSIONS: These results indicate that ICOS on activated
      T cells contributes to neointimal formation through the regulation of SMC
      proliferation. These findings provide insights into new therapeutic strategies
      for arteriosclerosis.

PMID- 16990559
TI  - Relationship between lipid abnormalities and insulin resistance in Japanese
      school children.
AB  - OBJECTIVE: Dyslipidemia and insulin resistance (IR) are risk factors for coronary
      heart disease (CHD) in adults. To help prevent the development of CHD, it may be
      useful to understand the relationship between lipid abnormalities and IR during
      childhood. METHODS AND RESULTS: IR was assessed by the homeostasis model
      approximation index. We studied 1175 Japanese school children (642 boys and 533
      girls), aged between 7 and 12 years. Obesity was defined by the body mass index
      standard deviation score (BMISD) (obese: BMISD > or = 2.0). BMISD was most
      significantly associated with IR in nonobese children (P=0.000). Associations of
      IR with lipid-related parameters were affected by BMISD. After being corrected by
      BMISD, in nonobese children, log triglycerides (TG), apoB and low-density
      lipoprotein (LDL) size in boys and log TG, LDL size, and high-density lipoprotein
      (HDL) cholesterol in girls were still significantly associated with IR (P=0.000
      to 0.017). In obese children, all parameters except for LDL cholesterol in boys
      and LDL size in girls were significantly associated with IR (P=0.000 to 0.030).
      Multiple regression analysis showed that log TG and LDL size in nonobese
      children, log TG in obese boys and LDL size in obese girls were independently
      associated with IR. Children with IIb and IV hyperlipidemia had significantly
      higher IR than those with normolipidemia and IIa, even after correcting for BMISD
      and age. CONCLUSIONS: Our results suggest that in addition to controlling body
      weight, it may be important for school children to characterize lipid phenotypes
      to prevent progression to CHD and/or type 2 diabetes and to identify subjects who
      are at high risk for these disorders.

PMID- 16990560
TI  - Is two out of three enough for ABCG1?

PMID- 16990561
TI  - Epidemiology complements immunology in the heart.

PMID- 16990562
TI  - Perplexity of plaque proteinases.

PMID- 16990563
TI  - A role for plasminogen activator inhibitor-1 in obesity: from pie to PAI?

PMID- 16990564
TI  - Summary of American Heart Association Diet and Lifestyle Recommendations revision
      2006.

PMID- 16990565
TI  - Mycophenolic acid is a potent inhibitor of angiogenesis.

PMID- 16990567
TI  - Cardiac overexpression of monocyte chemoattractant protein-1 in transgenic mice
      prevents cardiac dysfunction and remodeling after myocardial infarction.
AB  - Myocardial infarction (MI) is accompanied by inflammatory responses that lead to
      the recruitment of leukocytes and subsequent myocardial damage, healing, and scar
      formation. Because monocyte chemoattractant protein-1 (MCP-1) (also known as
      CCL2) regulates monocytic inflammatory responses, we investigated the effect of
      cardiac MCP-1 overexpression on left ventricular (LV) dysfunction and remodeling
      in a murine MI model. Transgenic mice expressing the mouse JE-MCP-1 gene under
      the control of the alpha-cardiac myosin heavy chain promoter (MHC/MCP-1 mice)
      were used for this purpose. MHC/MCP-1 mice had reduced infarct area and scar
      formation and improved LV dysfunction after MI. These mice also showed induction
      of macrophage infiltration and neovascularization; however, few bone marrow
      derived endothelial cells were detected in MHC/MCP-1 mice whose bone marrow was
      replaced with that of Tie2/LacZ transgenic mice. Flow cytometry analysis showed
      no increase in endothelial progenitor cells (CD34+/Flk-1+ cells) in MHC/MCP-1
      mice. Marked myocardial interleukin (IL)-6 secretion, STAT3 activation, and LV
      hypertrophy were observed after MI in MHC/MCP-1 mice. Furthermore, cardiac
      myofibroblasts accumulated after MI in MHC/MCP-1 mice. In vitro experiments
      revealed that a combination of IL-6 with MCP-1 synergistically stimulated and
      sustained STAT3 activation in cardiomyocytes. MCP-1, IL-6, and hypoxia directly
      promoted the differentiation of cardiac fibroblasts into myofibroblasts. Our
      results suggest that cardiac overexpression of MCP-1 induced macrophage
      infiltration, neovascularization, myocardial IL-6 secretion, and accumulation of
      cardiac myofibroblasts, thereby resulting in the prevention of LV dysfunction and
      remodeling after MI. They also provide a new insight into the role of cardiac MCP
      1 in the pathophysiology of MI.

PMID- 16990566
TI  - ROCK controls matrix synthesis in vascular smooth muscle cells: coupling
      vasoconstriction to vascular remodeling.
AB  - Tenascin-C (TN-C) is an extracellular matrix (ECM) protein expressed within
      remodeling systemic and pulmonary arteries (PAs), where it supports vascular
      smooth muscle cell (SMC) proliferation. Previously, we showed that A10 SMCs
      cultivated on native type I collagen possess a spindle-shaped morphology and do
      not express TN-C, whereas those on denatured collagen possess a well-defined F
      actin stress fiber network, a spread morphology, and they do express TN-C. To
      determine whether changes in cytoskeletal architecture control TN-C, SMCs on
      denatured collagen were treated with cytochalasin D, which decreased SMC
      spreading and activation of extracellular signal-regulated kinase 1/2 (ERK1/2),
      signaling effectors required for TN-C transcription. Next, to determine whether
      cell shape, dictated by the F-actin cytoskeleton, regulates TN-C, different
      geometries of SMCs (ranging from spread to round) were engineered on denatured
      collagen: as SMCs progressively rounded, ERK1/2 activity and TN-C transcription
      declined. Because RhoA and Rho kinase (ROCK) regulate cell morphology by
      controlling cytoskeletal architecture, we reasoned that these factors might also
      regulate TN-C. Indeed, SMCs on denatured collagen possessed higher levels of RhoA
      activity than those on native collagen, and blocking RhoA or ROCK activities
      attenuated SMC spreading, ERK1/2 activity, and TN-C expression in SMCs on
      denatured collagen. Thus, ROCK controls the configuration of the F-actin
      cytoskeleton and SMC shape in a manner that is permissive for ERK1/2-dependent
      production of TN-C. Finally, we showed that inhibition of ROCK activity
      suppresses SMC TN-C expression and disease progression in hypertensive rat PAs.
      Thus, in addition to its role in regulating vasoconstriction, ROCK also controls
      matrix production.

PMID- 16990568
TI  - Improvement of endothelial function by systemic transfusion of vascular
      progenitor cells.
AB  - Endothelial dysfunction is characterized by abnormalities in vasoreactivity and
      is a marker of the extent of atherosclerosis. Cellular repair by circulating
      progenitor cells of ongoing vascular injury may be essential for vascular
      integrity and function and may limit abnormalities in vasoreactivity.
      Apolipoprotein E-deficient (apoE-/-) mice were splenectomized and treated with
      high-cholesterol diet for 5 weeks, resulting in marked impairment of endothelium
      dependent vasodilation of aortic segments as compared with wild-type mice.
      Intravenous transfusion of 2x10(7) spleen-derived mononuclear cells (MNCs)
      isolated from wild-type mice on 3 consecutive days restored endothelium-dependent
      vasodilation in the apoE-/- mice, as measured 7, 14, and 45 days after
      transfusion. Histological analyses of aortic tissue identified fluorescent
      labeled, exogenously applied progenitor cells that expressed the endothelial cell
      marker CD31 in the endothelial cell layer of atherosclerotic lesions. Progenitor
      cell treatment led to increased vascular nitric oxide synthase activity.
      Transfusion of either in vitro-differentiated Dil-Ac-LDL/lectin-positive
      endothelial progenitor cells, CD11b-positive (monocyte marker), CD45R-positive (B
      cell marker), or Sca-1-positive (stem cell marker) MNC subpopulations
      significantly improved endothelium-dependent vasodilation, although these
      treatments were not as effective as transfusion of total MNCs. Depletion of MNCs
      of either CD11b-positive, CD45R-positive, or Sca-1-positive cells resulted in
      significant attenuation of endothelium-dependent vasodilation as compared with
      nondepleted MNCs; however, vasoreactivity was still significantly improved as
      compared with saline-treated apoE-/- mice. Intravenous transfusion of spleen
      derived MNCs improves endothelium-dependent vasodilation in atherosclerotic apoE
      /- mice, indicating an important role of circulating progenitor cells for the
      repair of ongoing vascular injury. More than 1 subpopulation of the MNC fraction
      seems to be involved in this effect.

PMID- 16990569
TI  - The gene encoding transforming growth factor beta 1 confers risk of ischemic
      stroke and vascular dementia.
AB  - BACKGROUND AND PURPOSE: Transforming growth factor-beta1 (TGF-beta1) is an anti
      inflammatory cytokine that plays an important role in cerebrovascular
      pathophysiology with protective activity against ischemia-induced neuronal death.
      We investigated the association of the polymorphism in TGFB1 with ischemic stroke
      and vascular dementia. METHODS: Three sequence variants in and around promoter
      and exons of TGFB1 gene were identified in 30 Koreans. Pro10Leu was selected for
      association study, and then control subjects (n=207) and patients with ischemic
      stroke (n=271) and vascular dementia (n=207) were screened. RESULTS: Subjects
      carrying Leu/Leu were susceptible to both ischemic stroke (odds ratio [OR]=1.63;
      P<0.05) and vascular dementia (OR=1.88; P<0.01). Analyses with stroke subtypes
      showed a strong association with small vessel occlusion (SVO, n=110; OR=2.07;
      P<0.01). Further analysis of SVO data partitioned by gender revealed the female
      specific association with Pro10Leu (OR=2.70; P<0.05). CONCLUSIONS: The Pro10Leu
      of TGFB1 might be a risk factor of ischemic stroke and vascular dementia,
      especially for SVO in females.

PMID- 16990571
TI  - High von Willebrand factor levels increase the risk of first ischemic stroke:
      influence of ADAMTS13, inflammation, and genetic variability.
AB  - BACKGROUND AND PURPOSE: Elevated von Willebrand factor (vWF) concentrations are
      associated with an increased risk of ischemic heart disease. Several factors
      influence vWF antigen levels and activity, including blood group, genetic
      variability, acute-phase response, and proteolysis by A Disintegrin and
      Metalloprotease with ThromboSpondin motif (ADAMTS13), a determinant of
      proteolytic cleavage of vWF. We assessed how these factors affect the relation
      between vWF and the occurrence of stroke to understand the underlying mechanism.
      METHODS: In a case-control study of 124 first-ever ischemic stroke patients and
      125 age- and sex-matched controls, we studied vWF antigen (vWF:Ag), vWF
      ristocetin cofactor activity (vWF:RCo), ADAMTS13 activity, the -1793C/G
      polymorphism in the vWF gene, and C-reactive protein. RESULTS: vWF antigen and
      activity levels were significantly higher in cases than in controls. The relative
      risk of ischemic stroke was highest in individuals in the upper quartile of
      vWF:Ag (odds ratio, 3.2; 95% CI, 1.4 to 7.5) and vWF:RCo (odds ratio, 2.1; 95%
      CI, 0.9 to 4.8) compared with individuals in the lowest quartiles. In individuals
      with ADAMTS13 in the lowest quartile, the relative risk of stroke was 1.7 (95%
      CI, 0.7 to 3.9) compared with the highest quartile. C-reactive protein, ADAMTS13,
      and genetic variation did not affect the association between vWF and the relative
      risk of stroke, whereas blood group did affect the association. CONCLUSIONS: vWF
      antigen and activity are associated with the occurrence of acute ischemic stroke.
      This relation is unaffected by the severity of the acute-phase response or by
      genetic variation or degradation.

PMID- 16990572
TI  - Borderzone infarction: stroke topography does not easily equate with stroke
      mechanism.

PMID- 16990573
TI  - Parental longevity, carotid atherosclerosis, and aortic arterial stiffness in
      adult offspring.
AB  - BACKGROUND AND PURPOSE: We examined the associations of parental longevity with
      carotid intima-media thickness, carotid plaques, and aortic arterial stiffness in
      adult offspring. METHODS: A population of 1117 volunteers who participated in the
      SUVIMAX Vascular Study (mean age, 59.7 years; 49.0% women) were included. Carotid
      femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid B
      mode ultrasound examination included measurements (at sites free of plaque) of
      intima-media thickness at the common carotid arteries and assessment of
      atherosclerotic plaques in the extracranial carotid arteries. RESULTS: The
      prevalence of carotid plaques in subjects whose fathers had died at <65 years, in
      those whose fathers were alive at 65 years but who had died by 80 years, and in
      those whose fathers were alive at 80 years was 40.4%, 30.4%, and 28.9%,
      respectively (P<0.001). The multivariate odds ratios of carotid plaques in the 3
      groups of paternal longevity, adjusted for conventional cardiovascular risk
      factors, were 1, 0.68 (95% CI, 0.48 to 0.96), and 0.69 (95% CI, 0.49 to 0.98),
      respectively. The mean common carotid arteries intima-media thickness was higher
      in subjects with premature paternal death in univariate (P<0.007) but not in
      multivariate (P=0.39) analyses. Mean PWV decreased with increasing paternal
      longevity in both univariate and multivariate analyses. The multivariate-adjusted
      means of PWV in the 3 groups of paternal longevity were 11.9+/-0.14, 11.7+/-0.12,
      and 11.0+/-0.12 m/s (P<0.0001), respectively. In contrast, neither B-mode
      ultrasound measurements nor PWV measurements were associated with maternal
      longevity. CONCLUSIONS: These results may indicate that there are modifications
      of structure and function of large arteries according to paternal longevity.

PMID- 16990575
TI  - Thrombolysis in stroke: a medicolegal quagmire.

PMID- 16990576
TI  - How much esprit is in ESPRIT?

PMID- 16990577
TI  - Uncertainties about thrombolysis for stroke should be addressed with large-scale
      randomized trials.

PMID- 16990578
TI  - Hyperinsulinemia and membrane microviscosity of erythrocytes as risk factors for
      stroke in patients with impaired glucose tolerance.

PMID- 16990579
TI  - Risk score for peri-interventional complications of carotid artery stenting.
AB  - BACKGROUND AND PURPOSE: Routinely available independent risk factors for the peri
      interventional outcome of patients undergoing elective carotid artery stenting
      (CAS) are lacking. The rationale of the study was to create a risk score
      identifying high-risk patients. METHODS: We prospectively enrolled 606
      consecutive patients assigned to CAS at a secondary care hospital. Various
      biochemical, clinical, and lesion-related risk factors were prospectively
      defined. The primary end point reflecting periprocedural complications
      encompassed minor and major stroke, nonfatal myocardial infarction and all-cause
      mortality within 30 days. RESULTS: Three percent of patients (n=18) experienced a
      nonfatal minor (n=13) or major (n=5) stroke. 1.3% of patients (n=8) died from
      fatal stroke (n=4) or other causes (n=4). No myocardial infarction was observed
      within 30 days after stenting. Multivariable analysis revealed diabetes mellitus
      with inadequate glycemic control (HbA1c > 7%), age > or = 80 years, ulceration of
      the carotid artery stenosis, and a contralateral stenosis > or = 50% as
      independent risk factors. A risk score formed with these variables showed a
      superior predictive value (C-statistic = 0.73) compared with single risk factors.
      The presence of 2 or more of these risk factors identified patients with a risk
      of 11% for a periprocedural complication compared with 2% in patients with a
      score of 0 or 1. CONCLUSIONS: In patients undergoing elective CAS, a risk score
      based on routinely accessible variables was able to identify patients at high
      risk for atherothrombotic events and all-cause death within 30 days after the
      intervention.

PMID- 16990580
TI  - Common carotid artery intima-media thickness: towards a definition of abnormal
      values in symptomatic cerebrovascular disease.

PMID- 16990582
TI  - Derivation of human embryonic stem cells from developing and arrested embryos.
AB  - Human embryonic stem cells (hESC) hold huge promise in modern regenerative
      medicine, drug discovery, and as a model for studying early human development.
      However, usage of embryos and derivation of hESC for research and potential
      medical application has resulted in polarized ethical debates since the process
      involves destruction of viable developing human embryos. Here we describe that
      not only developing embryos (morulae and blastocysts) of both good and poor
      quality but also arrested embryos could be used for the derivation of hESC.
      Analysis of arrested embryos demonstrated that these embryos express pluripotency
      marker genes such OCT4, NANOG, and REX1. Derived hESC lines also expressed
      specific pluripotency markers (TRA-1-60, TRA-1-81, SSEA4, alkaline phosphatase,
      OCT4, NANOG, TERT, and REX1) and differentiated under in vitro and in vivo
      conditions into derivates of all three germ layers. All of the new lines,
      including lines derived from late arrested embryos, have normal karyotypes. These
      results demonstrate that arrested embryos are additional valuable resources to
      surplus and donated developing embryos and should be used to study early human
      development or derive pluripotent hESC.

PMID- 16990583
TI  - Epicardial cells of human adults can undergo an epithelial-to-mesenchymal
      transition and obtain characteristics of smooth muscle cells in vitro.
AB  - Myocardial and coronary development are both critically dependent on epicardial
      cells. During cardiomorphogenesis, a subset of epicardial cells undergoes an
      epithelial-to-mesenchymal transition (EMT) and invades the myocardium to
      differentiate into various cell types, including coronary smooth muscle cells and
      perivascular and cardiac interstitial fibroblasts. Our current knowledge of
      epicardial EMT and the ensuing epicardium-derived cells (EPDCs) comes primarily
      from studies of chick and mouse embryonic development. Due to the absence of an
      in vitro culture system, very little is known about human EPDCs. Here, we report
      for the first time the establishment of cultures of primary epicardial cells from
      human adults and describe their immunophenotype, transcriptome, transducibility,
      and differentiation potential in vitro. Changes in morphology and beta-catenin
      staining pattern indicated that human epicardial cells spontaneously undergo EMT
      early during ex vivo culture. The surface antigen profile of the cells after EMT
      closely resembles that of subepithelial fibroblasts; however, only EPDCs express
      the cardiac marker genes GATA4 and cardiac troponin T. After infection with an
      adenovirus vector encoding the transcription factor myocardin or after treatment
      with transforming growth factor-beta1 or bone morphogenetic protein-2, EPDCs
      obtain characteristics of smooth muscle cells. Moreover, EPDCs can undergo
      osteogenesis but fail to form adipocytes or endothelial cells in vitro. Cultured
      epicardial cells from human adults recapitulate at least part of the
      differentiation potential of their embryonic counterparts and represent an
      excellent model system to explore the biological properties and therapeutic
      potential of these cells.

PMID- 16990584
TI  - Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set
      of disease-associated genes and reveals the clinical significance of Wilms' tumor
      gene 1 (WT1).
AB  - This study was aimed at the characterization of a gene expression signature of
      the pluripotent hematopoietic CD34(+) stem cell in idiopathic myelofibrosis (IM),
      which would eventually provide novel pathogenetic insights and/or
      diagnostic/prognostic information. Aberrantly regulated genes were revealed by
      transcriptome comparative microarray analysis of normal and IM CD34(+) cells;
      selected genes were also assayed in granulocytes. One-hundred seventy four
      differentially expressed genes were identified and in part validated by
      quantitative polymerase chain reaction. Altered gene expression was corroborated
      by the detection of abnormally high CD9 or CD164, and low CXCR4, membrane protein
      expression in IM CD34(+) cells. According to class prediction analysis, a set of
      eight genes (CD9, GAS2, DLK1, CDH1, WT1, NFE2, HMGA2, and CXCR4) properly
      recognized IM from normal CD34(+) cells. These genes were aberrantly regulated
      also in IM granulocytes that could be reliably differentiated from control
      polycythemia vera and essential thrombocythemia granulocytes in 100% and 81% of
      cases, respectively. Abnormal expression of HMGA2 and CXCR4 in IM granulocytes
      was dependent on the presence and the mutational status of JAK2(V617F) mutation.
      The expression levels of both CD9 and DLK1 were associated with the platelet
      count, whereas higher WT1 expression levels identified IM patients with more
      active disease, as revealed by elevated CD34(+) cell count and higher severity
      score. In conclusion, molecular profiling of IM CD34(+) cells uncovered a limited
      number of genes with altered expression that, beyond their putative role in
      disease pathogenesis, are associated with patients' clinical characteristics and
      may have potential prognostic application.

PMID- 16990585
TI  - Dppa2 and Dppa4 are closely linked SAP motif genes restricted to pluripotent
      cells and the germ line.
AB  - Despite the enormous medical potential of ESCs, the molecular mechanisms
      conferring the ability to differentiate into all cell types of the embryo remain
      elusive. We used an in silico approach to identify genes expressed exclusively in
      mouse preimplantation embryos and pluripotent cell lines. Two of these genes were
      developmental pluripotency-associated gene 2 (Dppa2) and Dppa4, which we show are
      closely linked genes encoding putative nuclear SAP domain proteins expressed in
      human and mouse pluripotent stem cells and germ cell tumor-derived embryonal
      carcinoma cells. In the mouse, these genes are transcribed in germinal vesicle
      stage oocytes and throughout the cleavage stages of embryogenesis. They then
      become restricted to the pluripotent inner cell mass of blastocysts and are
      subsequently downregulated. After gastrulation, Dppa2 and Dppa4 are expressed
      only in the developing germ line, showing that these genes mark cells of the
      pluripotent cycle. In the germ line, both genes are downregulated as the germ
      cells commit to the oogenic pathway or soon after commitment to the spermatogenic
      pathway. We have observed similar germ line expression profiles for other
      pluripotent markers, and these results are consistent with the hypothesis that
      pluripotent markers must be downregulated during fetal germ line development, a
      process that may be required to facilitate appropriate germ line differentiation.
      The study of expression and function of pluripotent markers such as Dppa2 and
      Dppa4 is likely to unveil new aspects of the regulation of pluripotency and germ
      line development in mammals.

PMID- 16990586
TI  - Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of
      neural stem cells toward a site of spinal cord injury.
AB  - Neural stem/progenitor cells (NSPCs) migrate toward a damaged area of the central
      nervous system (CNS) for the purpose of limiting and/or repairing the damage.
      Although this migratory property of NSPCs could theoretically be exploited for
      cell-based therapeutics of CNS diseases, little is known of the mechanisms
      responsible for migratory responses of NSPCs. Here, we found that sphingosine 1
      phosphate (Sph-1-P), a physiological lysophospholipid mediator, had a potent
      chemoattractant activity for NSPCs, in which, of Sph-1-P receptors, S1P(1) was
      abundantly expressed. Sph-1-P-induced NSPC migration was inhibited by the
      pretreatment with pertussis toxin, Y-27632 (a Rho kinase inhibitor), and VPC23019
      (a competitive inhibitor of S1P(1) and S1P(3)). Sph-1-P does not act as
      intracellular mediator or in an autocrine manner, because [(3)H]sphingosine,
      incorporated into NSPCs, was mainly converted to ceramide and sphingomyeline
      intracellularly, and the stimulation-dependent formation and extracellular
      release of Sph-1-P were not observed. Further, Sph-1-P concentration in the
      spinal cord was significantly increased at 7 days after a contusion injury, due
      to accumulation of microglia and reactive astrocytes in the injured area. This
      locally increased Sph-1-P concentration contributed to the migration of in vivo
      transplanted NSPCs through its receptor S1P(1), given that lentiviral
      transduction of NSPCs with a short hairpin RNA interference for S1P(1) abolished
      in vivo NSPC migration toward the injured area. This is the first report to
      identify a physiological role for a lipid mediator in NSPC migration toward a
      pathological area of the CNS and further indicates that the Sph-1-P/S1P(1)
      pathway may have therapeutic potential for CNS injuries.

PMID- 16990587
TI  - Production of green fluorescent protein transgenic embryonic stem cells using the
      GENSAT bacterial artificial chromosome library.
AB  - Transgenic green fluorescent protein (GFP) reporter embryonic stem (ES) cells are
      powerful tools for studying gene regulation and lineage choice during
      development. Here we present a rapid method for the generation of ES cells
      expressing GFP under the control of selected genes. Bacterial artificial
      chromosomes (BACs) from a previously constructed GFP transcriptional fusion
      library (Gene Expression Nervous System Atlas [GENSAT]) were modified for use in
      ES cells, and multiple BAC transgenic ES cell lines were generated. Specific GFP
      expression in transgenic cell lines was confirmed during neural differentiation
      marking neural stem cells, neuronal precursors, and glial progeny by Hes5, Dll1,
      and GFAP, respectively. GFP was dynamically regulated in ES cell progeny in
      response to soluble factors that inhibit Notch signaling and a factor that
      directs astroglial fate choice. Our protocols provide a simple and efficient
      strategy to utilize the whole GENSAT BAC library to create hundreds of novel
      fluorescent cell lines for use in ES cell biology.

PMID- 16990588
TI  - Chromatin-remodeling factors allow differentiation of bone marrow cells into
      insulin-producing cells.
AB  - Type 1 diabetes is caused by the destruction of pancreatic beta-cells by T cells
      of the immune system. Islet transplantation is a promising therapy for diabetes
      mellitus. Bone marrow stem cells (BMSC) have the capacity to differentiate into
      various cell lineages including endocrine cells of the pancreas. To investigate
      the conditions that allow BMSC to differentiate into insulin-producing cells, a
      novel in vitro method was developed by using the histone deacetylase inhibitor,
      trichostatin A (TSA). BMSC, cultured in presence of TSA, differentiated into
      islet-like clusters under appropriate culture conditions. These islet-like
      clusters were similar to the cells of the islets of the pancreas. The islet-like
      clusters showed endocrine gene expression typical for pancreatic beta-cell
      development and function, such as insulin (I and II), glucagon, somatostatin,
      GLUT-2, pancreatic duodenal homeobox-1 (PDX-1), and Pax 4. Immunocytochemistry
      confirmed islet-like clusters contained pancreatic hormones. The colocalization
      of insulin and C-peptide was also observed. Enzyme-linked immunosorbent assay
      analysis demonstrated that insulin secretion was regulated by glucose. Western
      blot analysis demonstrated the presence of stored insulin. Electron microscopy of
      the islet-like cells revealed an ultrastructure similar to that of pancreatic
      beta-cells, which contain insulin granules within secretory vesicles. These
      findings suggest that histone-deacetylating agents could allow the
      differentiation of BMSC into insulin-producing beta-cells.

PMID- 16990590
TI  - Thrombin stimulation of p38 MAP kinase in human platelets is mediated by ADP and
      thromboxane A2 and inhibited by cGMP/cGMP-dependent protein kinase.
AB  - p38 MAP kinase in human platelets is activated by platelet agonists including
      thrombin, thromboxane A2 (TxA2), ADP, and others. However, both upstream
      mechanisms of p38 MAP kinase activation, and their downstream sequelae, are
      presently controversial and essentially unclear. Certain studies report
      sequential activation of cGMP-dependent protein kinase (PKG) and p38/ERK pathways
      by platelet agonists, leading to integrin activation and secretion, whereas
      others establish an essential role of Src/ERK-mediated TxA2 generation for
      fibrinogen receptor activation in human platelets. Here, we show that ADP
      secreted from platelet-dense granules, and subsequent activation of P2Y12
      receptors, as well as TxA2 release are important upstream mediators of p38 MAP
      kinase activation by thrombin. However, p38 MAP kinase activation did not
      significantly contribute to calcium mobilization, P-selectin expression,
      alphaIIbbeta3 integrin activation, and aggregation of human platelets in response
      to thrombin. Finally, PKG activation did not stimulate, but rather inhibited, p38
      MAP kinase in human platelets.

PMID- 16990591
TI  - Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic
      myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure.
AB  - Developing strategies to counteract imatinib resistance constitutes a challenge
      in chronic myelogenous leukemia (CML). Therapy with the tyrosine kinase
      inhibitors nilotinib (AMN107) and dasatinib (BMS-354825) has produced high rates
      of hematologic and cytogenetic response. Src kinase activation has been linked to
      Bcr-Abl-mediated leukemogenesis and CML progression. In addition to binding Abl
      kinase with less stringent conformational requirements than imatinib, dasatinib
      is a potent Src kinase inhibitor. In the current study, we report on 23 patients
      with CML (19 of them in accelerated or blastic phases) treated with dasatinib
      after treatment failure with both imatinib and nilotinib. More than half (13;
      57%) of 23 patients responded to dasatinib: 10 (43%) had a complete hematologic
      response (CHR), including 7 (30%) who had a cytogenetic response (2 complete, 4
      partial, and 1 minor). These results suggest that dasatinib may be active in some
      patients after failure with both imatinib and nilotinib.

PMID- 16990592
TI  - Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal
      protein required for the maturation of 40S ribosomal subunits.
AB  - Diamond-Blackfan anemia (DBA) typically presents with red blood cell aplasia that
      usually manifests in the first year of life. The only gene currently known to be
      mutated in DBA encodes ribosomal protein S19 (RPS19). Previous studies have shown
      that the yeast RPS19 protein is required for a specific step in the maturation of
      40S ribosomal subunits. Our objective here was to determine whether the human
      RPS19 protein functions at a similar step in 40S subunit maturation. Studies
      where RPS19 expression is reduced by siRNA in the hematopoietic cell line, TF-1,
      show that human RPS19 is also required for a specific step in the maturation of
      40S ribosomal subunits. This maturation defect can be monitored by studying rRNA
      processing intermediates along the ribosome synthesis pathway. Analysis of these
      intermediates in CD34- cells from the bone marrow of patients with DBA harboring
      mutations in RPS19 revealed a pre-rRNA-processing defect similar to that observed
      in TF-1 cells where RPS19 expression was reduced. This defect was observed to a
      lesser extent in CD34+ cells from patients with DBA who have mutations in RPS19.

PMID- 16990593
TI  - Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and
      dexamethasone in systemic AL amyloidosis.
AB  - High-dose melphalan with stem-cell transplantation is believed to be the most
      effective treatment for systemic light-chain (AL) amyloidosis, but many patients
      are ineligible because of the extent of their disease, and treatment-related
      mortality (TRM) remains substantial. We report the use of a risk-adapted oral
      regimen of cyclophosphamide, thalidomide, and dexamethasone (CTD) or attenuated
      CTD (CTDa) in 75 patients with advanced AL amyloidosis, including 44 patients
      with clonal relapse after prior therapy. Fifty-one (68%) patients received CTD
      and 24 (32%) received CTDa. A hematologic response occurred in 48 (74%) of 65
      evaluable patients, including complete responses in 14 (21%) and partial
      responses in 34 (53%) cases. Median estimated overall survival (OS) from
      commencement of treatment was 41 months, and from diagnosis median was not
      reached with a median follow-up of 22 months. Three-year estimated OS was 100%
      and 82% among complete and partial hematologic responders, respectively. Toxicity
      necessitating cessation of therapy occurred in 8% and was at least grade 2 in 52%
      of patients. TRM was 4%. The clonal response rates to CTD reported here are
      higher than any previously reported nontransplantation regimen in AL amyloidosis,
      and risk adaptation allows its use in poorer risk patients. CTD merits
      prospective randomized study.

PMID- 16990594
TI  - Functional characterization of natural telomerase mutations found in patients
      with hematologic disorders.
AB  - Human telomerase hTERC RNA serves as a template for the catalytic hTERT protein
      to synthesize telomere repeats at chromosome ends. We have recently shown that
      some patients with bone marrow failure syndromes are heterozygous carriers for
      hTERC or hTERT mutations. These sequence variations usually lead to a compromised
      telomerase function by haploinsufficiency. Here, we provide functional
      characterization of an additional 8 distinct hTERT sequence variants and 5 hTERC
      variants that have recently been identified in patients with dyskeratosis
      congenita (DC) or aplastic anemia (AA). Among the mutations, 2 are novel
      telomerase variants that were identified in our cohort of patients. Whereas most
      of the sequence variants modulate telomerase function by haploinsufficiency, 2
      hTERC variants with sequence changes located within the template region appear to
      act in a dominant-negative fashion. Inherited telomerase gene mutations,
      therefore, operate by various mechanisms to shorten telomere lengths, leading to
      limited marrow stem cell reserve and renewal capacity in patients with
      hematologic disorders.

PMID- 16990595
TI  - Expression of Livin, an antiapoptotic protein, is an independent favorable
      prognostic factor in childhood acute lymphoblastic leukemia.
AB  - Livin, a member of the inhibitor of apoptosis proteins, has been considered to be
      a poor prognostic marker in malignancies. However, little is known about the
      clinical relevance of Livin expression in childhood acute lymphoblastic leukemia
      (ALL). In this study, the expression of Livin was analyzed in 222 patients with
      childhood ALL using quantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) to investigate a possible association with the clinical features at
      diagnosis and treatment outcomes. Both Livin expression rates and expression
      levels were higher in patients with favorable prognostic factors. The expression
      rate was also higher in patients with a favorable day 7 bone marrow response to
      induction chemotherapy (P<.001). The Livin expression was related to the absence
      of relapse (P<.001). Similarly, the relapse-free survival rate (+/-95% CI) was
      higher in patients with Livin expression than in patients without Livin
      expression (97.9%+/-4.0% versus 64.9%+/-11.8%, P<.001). Multivariate analysis for
      relapse-free survival demonstrated that Livin expression was an independent
      favorable prognostic factor in childhood ALL (P=.049). This study suggests that
      Livin expression is a novel prognostic marker in childhood ALL and thus needs to
      be incorporated into the patient stratification and treatment protocols.

PMID- 16990596
TI  - Identification of a 2-stage platelet aggregation process mediating shear
      dependent thrombus formation.
AB  - Disturbances of blood flow at sites of atherosclerotic plaque rupture are one of
      the key pathogenic events promoting platelet activation and arterial thrombus
      formation. Shear effects of platelets have been extensively investigated in
      vitro; however, the mechanisms by which shear promotes platelet aggregation in
      vivo remain incompletely understood. By employing high-resolution imaging
      techniques to in vitro and in vivo thrombosis models, we demonstrate a unique
      mechanism initiating shear-dependent platelet aggregation involving aggregate
      formation between discoid platelets. These discoid platelet aggregates are
      initially unstable and result from the development of membrane tethers between
      coadhering platelets. Tether formation involves the adhesive function of
      GPIb/V/IX and integrin alphaIIbbeta3, and conversion of discoid platelet
      aggregates into stable aggregates requires released ADP. The efficiency of this
      process is regulated by 3 independent variables, including the reactivity of the
      adhesive substrate, the level of shear flow, and the platelet density at the
      adhesive surface. These studies identify a new mechanism initiating platelet
      aggregation that is critically influenced by shear, physical proximity between
      translocating platelets, and membrane tether formation. Moreover, they provide a
      model to explain how the discoid morphology of platelets facilitates the
      maintenance of adhesive interactions with thrombogenic surfaces under high shear
      stress conditions.

PMID- 16990597
TI  - Low rhodamine 123 retention identifies long-term human hematopoietic stem cells
      within the Lin-CD34+CD38- population.
AB  - Progress to uncover the molecular and cellular regulators that govern human
      hematopoietic stem cell (HSC) fate has been impeded by an inability to obtain
      highly purified fractions of HSCs. We report that the rhodamine 123 (Rho 123) dye
      effluxing fraction of the Lin-CD34+CD38- population contains SCID-repopulating
      cells (SRCs) capable of long-term repopulation in primary nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mice. Purification based on
      Rho uptake led to a 4-fold enrichment of SRCs in the Lin-CD34+CD38- fraction,
      with a frequency of 1 SRC in 30 Lin-CD34+CD38-Rholo cells. The Lin-CD34+CD38
      Rholo fraction also possesses long-term self-renewal capacity as measured by
      serial transplantation totaling more than 20 weeks. We conclude that Rho dye
      efflux provides an additional means of purifying human HSCs in the quest to
      achieve homogeneous populations of primitive cells for both experimental and
      therapeutic applications.

PMID- 16990598
TI  - Solenopsin, the alkaloidal component of the fire ant (Solenopsis invicta), is a
      naturally occurring inhibitor of phosphatidylinositol-3-kinase signaling and
      angiogenesis.
AB  - Phosphatidylinositol-3-kinase (PI3K), and its downstream effector Akt, or protein
      kinase Balpha (PKBalpha), play a major regulatory role in control of apoptosis,
      proliferation, and angiogenesis. PI3K and Akt are amplified or overexpressed in a
      number of malignancies, including sarcomas, ovarian cancer, multiple myeloma, and
      melanoma. This pathway regulates production of the potent angiogenic factor
      vascular endothelial growth factor (VEGF), and protects tumor cells against both
      chemotherapy and reactive oxygen-induced apoptosis through phosphorylation of
      substrates such as apoptotic peptidase-activating factor-1 (APAF-1), forkhead
      proteins, and caspase 9. Given its diverse actions, compounds that suppress the
      PI3K/Akt pathway have potential pharmacologic utility as angiogenesis inhibitors
      and antineoplastic agents. Using the SVR angiogenesis assay, a screen of natural
      products, we isolated the alkaloid solenopsin, and found that it is a potent
      angiogenesis inhibitor. We also found that solenopsin inhibits the PI3K signaling
      pathway in cells upstream of PI3K, which may underlie its affects on
      angiogenesis. Consistent with inhibition of the activation of PI3K, solenopsin
      prevented the phosphorylation of Akt and the phosphorylation of its substrate
      forkhead box 01a (FOXO1a), a member of the forkhead family of transcription
      factors. Interestingly, solenopsin also inhibited Akt-1 activity in an ATP
      competitive manner in vitro without affecting 27 of 28 other protein kinases
      tested.

PMID- 16990600
TI  - Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out
      mice by promoting de novo leukocyte recruitment.
AB  - Vascular endothelial growth factor-A is widely used in clinical trials for the
      treatment of cardiac ischemia. VEGF-A was recently suggested to act in a
      proinflammatory manner, which could aggravate adjacent atherogenesis in VEGF-A
      based therapy. To assess potential bystander effects, VEGF-A was focally
      overexpressed in advanced atherosclerotic plaques in ApoE-/- mice. Sheer-induced
      carotid artery plaques were transluminally incubated with Ad.hVEGF-A leading to
      neointimal overexpression of VEGF-A. Ad.hVEGF-A treatment of pre-existing lesions
      was seen to promote plaque expansion, with a concomitant increase in macrophage
      and lipid content, whereas it lowered collagen content. In general, Ad.hVEGF-A
      treated plaques displayed a more vulnerable phenotype. VEGF-A overexpression was
      not accompanied by increased microvessel development in the neointima, suggesting
      that VEGF-A destabilizes atherosclerotic plaques through an angiogenesis
      independent mechanism. Intravital microscopy confirmed that treatment with
      Ad.hVEGF-A led to an increased monocyte adhesion, which was mediated by a VCAM
      1/PECAM-1-dependent pathway. VEGF-A indeed induced a differential expression of
      VCAM-1 and PECAM-1 in endothelial cells. Our data underline the importance of
      regular monitoring of stenotic vessels adjacent to the site of VEGF-A
      application. We propose that VCAM-1/PECAM-1-directed cotherapy may be an
      efficient strategy to prevent bystander effects of focal VEGF-A therapy in
      patients suffering from cardiovascular disease.

PMID- 16990599
TI  - Human T-cell leukemia virus type-1 Tax oncoprotein regulates G-protein signaling.
AB  - Human T-cell leukemia virus type-1 (HTLV-1) is associated with adult T-cell
      leukemia (ATL) and neurological syndromes. HTLV-1 encodes the oncoprotein Tax-1,
      which modulates viral and cellular gene expression leading to T-cell
      transformation. Guanine nucleotide-binding proteins (G proteins) and G protein
      coupled receptors (GPCRs) constitute the largest family of membrane proteins
      known and are involved in the regulation of most biological functions. Here, we
      report an interaction between HTLV-1 Tax oncoprotein and the G-protein beta
      subunit. Interestingly, though the G-protein beta subunit inhibits Tax-mediated
      viral transcription, Tax-1 perturbs G-protein beta subcellular localization.
      Functional evidence for these observations was obtained using conditional Tax-1
      expressing transformed T-lymphocytes, where Tax expression correlated with
      activation of the SDF-1/CXCR4 axis. Our data indicated that HTLV-1 developed a
      strategy based on the activation of the SDF-1/CXCR4 axis in the infected cell;
      this could have tremendous implications for new therapeutic strategies.

PMID- 16990601
TI  - Phenotypic heterogeneity is an evolutionarily conserved feature of the
      endothelium.
AB  - Mammalian endothelial cells (ECs) display marked phenotypic heterogeneity. Little
      is known about the evolutionary mechanisms underlying EC heterogeneity. The last
      common ancestor of hagfish and gnathostomes was also the last common ancestor of
      all extant vertebrates, which lived some time more than 500 million years ago.
      Features of ECs that are shared between hagfish and gnathostomes can be inferred
      to have already been present in this ancestral vertebrate. The goal of this study
      was to determine whether the hagfish endothelium displays phenotypic
      heterogeneity. Electron microscopy of the aorta, dermis, heart, and liver
      revealed ultrastructural heterogeneity of the endothelium. Immunofluorescent
      studies demonstrated marked differences in lectin binding between vascular beds.
      Intravital microscopy of the dermis revealed histamine-induced adhesion of
      leukocytes in capillaries and postcapillary venules, but no such adhesion in
      arterioles. Together, these data suggest that structural, molecular, and
      functional heterogeneity of the endothelium evolved as an early feature of this
      cell lineage.

PMID- 16990602
TI  - Successful bone marrow transplantation for IPEX syndrome after reduced-intensity
      conditioning.
AB  - Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome
      is a rare, fatal autoimmune disorder caused by mutations in the FOXP3 gene
      leading to the disruption of signaling pathways involved in regulatory T
      lymphocyte function. Lifelong multiagent immunosuppression is necessary to
      control debilitating autoimmune manifestations such as colitis and food
      allergies. Allogeneic hematopoietic stem cell transplantation (HSCT) can restore
      T-cell regulatory function but has been previously associated with poor outcome.
      We describe successful HSCT in 4 patients with IPEX syndrome using a novel
      reduced-intensity conditioning regimen that resulted in stable donor engraftment,
      reconstitution of FOXP3+ T regulatory CD4+ cells, and amelioration of
      gastrointestinal symptoms.

PMID- 16990603
TI  - MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid
      leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation.
AB  - MK-0457 (VX-680) is a small-molecule aurora kinase (AK) inhibitor with
      preclinical antileukemia activity. The T315I BCR-ABL mutation mediates resistance
      to imatinib, nilotinib, and dasatinib. MK-0457 has in vitro activity against
      cells expressing wild-type or mutated BCR-ABL, including the T315I BCR-ABL
      mutation. Three patients with T315I abl-mutated chronic myeloid leukemia (CML) or
      Philadelphia chromosome (Ph)-positive acute lymphocytic leukemia (ALL) have
      achieved clinical responses to doses of MK-04547 that are not associated with
      adverse events. Higher MK-0457 dose levels were associated with clinical
      responses and down-regulation of CrkL phosphorylation in leukemia cells. The
      possible role of AK inhibition in these clinical responses requires further
      investigation. The currently reported cases are the first observed clinical
      activity of a kinase inhibitor against the T315I phenotype. The observation of
      responses in 3 patients with T315I phenotype-refractory CML or Ph-positive ALL,
      at doses of MK-0457 associated with no significant extramedullary toxicity, is
      very encouraging.

PMID- 16990604
TI  - IgA Fc receptor I signals apoptosis through the FcRgamma ITAM and affects tumor
      growth.
AB  - The IgA Fc receptor (FcalphaRI) has dual proinflammatory and anti-inflammatory
      functions that are transmitted through the immunoreceptor tyrosine-based
      activation motifs (ITAMs) of the associated FcRgamma subunit. Whereas the
      involvement of FcalphaRI in inflammation is well documented, little is known of
      its anti-inflammatory mechanisms. Here we show that monomeric targeting of
      FcalphaRI by anti-FcalphaRI Fab or serum IgA triggers apoptosis in human
      monocytes, monocytic cell lines, and FcalphaRI+ transfectants. However, the
      physiologic ligand IgA induced apoptosis only when cells were cultured in low
      serum conditions, indicating differences with induction of anti-inflammatory
      signaling. Apoptosis signaling required the FcRgamma ITAM, as cells transfected
      with FcalphaRI or with a chimeric FcalphaRI-FcRgamma responded to death
      activating signals, whereas cells expressing a mutated FcalphaRI(R209L) unable to
      associate with FcRgamma, or an ITAM-mutated chimeric FcalphaRI-FcRgamma, did not
      respond. FcalphaRI-mediated apoptosis signals were blocked by treatment with the
      pan-caspase inhibitor zVAD-fmk, involved proteolysis of procaspase-3, and
      correlated negatively with SHP-1 concentration. Anti-FcalphaRI Fab treatment of
      nude mice injected subcutaneously with FcalphaRI+ mast-cell transfectants
      prevented tumor development and halted the growth of established tumors. These
      findings demonstrate that, on monomeric targeting, FcalphaRI functions as an
      FcRgamma ITAM-dependent apoptotic module that may be fundamental for controlling
      inflammation and tumor growth.

PMID- 16990605
TI  - A randomized comparison of bypassing agents in hemophilia complicated by an
      inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study.
AB  - The development of inhibitory antibodies to factor VIII is a serious complication
      of hemophilia. FEIBA (factor VIII inhibitor-bypassing activity), an activated
      prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor VIIa
      (rFVIIa), are used as hemostatic bypassing agents in treating patients with
      inhibitors. The FENOC study was designed to test equivalence of the products in
      the treatment of ankle, knee, and elbow joint bleeding. A prospective, open
      label, randomized, crossover, equivalency design was used. The parameters of
      interest were the percentage of patients who reported efficacy in response to
      FEIBA and the percentage that reported efficacy in response to NovoSeven. A
      difference in these percentages of no more than 15% was determined to be a
      clinically acceptable magnitude for equivalence of the 2 products. The primary
      outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes
      contributed by 48 participants were analyzed. The criterion for declaring the 2
      products equivalent at 6 hours was not met; however, the confidence interval of
      the difference in percentages of efficacy reported for each product only slightly
      exceeded the 15% boundary (-11.4%-15.7%), P=.059. FEIBA and NovoSeven appear to
      exhibit a similar effect on joint bleeds, although the efficacy between products
      is rated differently by a substantial proportion of patients. This trial was
      registered at www.clinicaltrials.gov as #NCT00166309.

PMID- 16990606
TI  - Rho GTPase Rac1 is critical for neutrophil migration into the lung.
AB  - Neutrophils are critical in the inflammatory process by moving rapidly to tissue
      sites of inflammation. Members of the small Rho GTPase family, Rac1, Rac2, CDC42,
      and RhoA, are central regulators of cell migration by cytoskeleton rearrangement.
      The role of Rac1 in neutrophil migration related to inflammatory processes has
      remained elusive and has yet to be determined in physiologic in vivo models. We
      previously demonstrated a role for Rac1 in tail retraction. Here, we present
      evidence that Rac1-mediated uropod formation may be due to crosstalk with a
      related Rho GTPase RhoA. To assess the physiologic relevance of these findings,
      we used adoptive transfer of Rac1flox/flox bone marrow cells which allows
      postengraftment in vivo deletion of Rac1 only in blood cells. We examined the
      specific role of Rac1 in neutrophil migration into the lung during the
      inflammatory process induced by formyl-methionyl-leucyl-phenylalanine exposure.
      The loss of Rac1 activity in neutrophils is associated with a significant
      decreased neutrophil recruitment into lung alveolar and attenuation of
      emphysematous lesions. Overall, this study suggests that Rac1 is a physiologic
      integrator of signals for neutrophil recruitment into lung tissue during an
      inflammatory response.

PMID- 16990607
TI  - Early acquisition of cytolytic function and transcriptional changes in a primary
      CD8+ T-cell response in vivo.
AB  - Functional studies show that programming of CD8+ T cells occurs early after
      initial antigen encounter within as little as 2 hours. To define the molecular
      basis of these events, we transferred TCR transgenic T cells from F5 Rag-/- mice
      into naive recipients and stimulated them with recombinant vaccinia expressing
      the immunodominant influenza epitope NP366-374. Transcription in epitope-specific
      cytotoxic T lymphocytes (CTLs) was analyzed using Affymetrix 430 2.0 GeneChips
      and quantitative polymerase chain reaction (PCR). We demonstrated an early
      transcriptional burst with the greatest number of genes reaching peak expression
      12 hours after stimulation. Using in vivo cytotoxicity assays we demonstrated
      that early up-regulation of cytolytic genes was accompanied by acquisition of
      killing capacity within 24 hours of stimulation. However, T-cell proliferation
      was not observed until 48 hours. We therefore conclude that clonal expansion
      rather than acquisition of effector function is the rate-limiting step in the
      development of a primary CTL response.

PMID- 16990608
TI  - Tissue factor deficiency and PAR-1 deficiency are protective against renal
      ischemia reperfusion injury.
AB  - Ischemia/reperfusion (IR) injury is a leading cause of acute renal failure and an
      important contributor to allograft damage. Tissue factor (TF) is up-regulated
      during IR, and TF inhibition reduces renal injury. However, the underlying
      mechanisms by which TF contributes to injury have not been elucidated. We
      postulated that TF contributes to IR injury by production of coagulation
      proteases and subsequent signaling by protease activated receptor (PARs). We
      compared renal injury after 25 minutes of bilateral renal ischemia and varying
      periods of reperfusion in C57BL/6 mice, those expressing low levels of TF (low
      TF), hirudin-treated C57BL/6, and mice lacking either PAR-1 or PAR-2. C57BL/6
      mice developed severe renal failure and died within 48 hours of reperfusion. In
      contrast, low-TF, hirudin-treated C57BL/6, and PAR-1-/- mice were protected from
      renal failure and had reduced mortality, tubular injury, neutrophil accumulation,
      and lower levels of the chemokines KC and MIP-2. Importantly, PAR-1-/- mice had
      lower chemokine levels despite up-regulation of TF and fibrin deposition. In
      addition, treating PAR-1-/- mice with hirudin conferred no additional benefit.
      Somewhat surprisingly, PAR-2 deficiency did not protect from renal failure. These
      experiments indicate that increased TF activity after renal IR leads to increased
      CXC chemokine expression and subsequent neutrophil-mediated injury predominantly
      by thrombin-dependent PAR-1 signaling.

PMID- 16990609
TI  - Smad1 expands the hemangioblast population within a limited developmental window.
AB  - Bone morphogenetic protein (BMP) signaling is an important regulator of
      hematovascular development. However, the progenitor population that responds to
      BMP signaling is undefined, and the relative role of downstream mediators
      including Smad1 is unclear. We find that Smad1 shows a distinctive expression
      profile as embryonic stem (ES) cells undergo differentiation in the embryoid body
      (EB) system, with peak levels in cell populations enriched for the hemangioblast.
      To test the functional relevance of this observation, we generated an ES cell
      line that allows temporal control of ectopic Smad1 expression. Continuous
      expression of Smad1 from day 2 of EB culture does not disturb hematopoiesis,
      according to colony assays. In contrast, a pulse of Smad1 expression exclusively
      between day 2 and day 2.25 expands the population of progenitors for primitive
      erythroblasts and other hematopoietic lineages. This effect correlates with
      increased levels of transcripts encoding markers for the hemangioblast, including
      Runx1, Scl, and Gata2. Indeed, the pulse of Smad1 induction also expands the
      blast colony-forming cell (BL-CFC) population at a level that is fully sufficient
      to explain subsequent increases in hematopoiesis. Our data demonstrate that Smad1
      expression is sufficient to expand the number of cells that commit to
      hemangioblast fate.

PMID- 16990610
TI  - Aberrant transcriptional regulation of the MLL fusion partner EEN by AML1-ETO and
      its implication in leukemogenesis.
AB  - The EEN (extra eleven nineteen) gene, located on chromosome 19p13, was cloned as
      a fusion with MLL from a patient with acute myeloid leukemia (AML) with
      translocation t(11;19)(q23;p13). In this study, we characterized the genomic
      structure of the EEN gene, including its 5' regulatory region and transcription
      start site (TSS). We found that Sp1 could bind to the guanine-cytosine (GC)
      stretch of the EEN promoter and was critical for the normal EEN expression,
      whereas the leukemia-associated fusion protein AML1-ETO could aberrantly
      transactivate the EEN gene through an AML1 binding site. Of note, overexpressed
      EEN showed oncogenic properties, such as transforming potential in NIH3T3 cells,
      stimulating cell proliferation, and increasing the activity of transcriptional
      factor AP-1. Retroviral transduction of EEN increased self-renewal and
      proliferation of murine hematopoietic progenitor cells. Moreover, Kasumi-1 and
      HL60-cell growth was inhibited with down-regulation of EEN by RNAi. These
      findings demonstrate that EEN might be a common target in 2 major types of AML
      associated with MLL or AML1 translocations, and overexpression of EEN may play an
      essential role in leukemogenesis.

PMID- 16990611
TI  - IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus
      formation.
AB  - Defective regulation of platelet activation/aggregation is a predominant cause
      for arterial thrombosis, the major complication of atherosclerosis triggering
      myocardial infarction and stroke. A central regulatory pathway conveying
      inhibition of platelet activation/aggregation is nitric oxide (NO)/cyclic GMP
      (cGMP) signaling by cGMP-dependent protein kinase I (cGKI). However, the
      regulatory cascade downstream of cGKI mediating platelet inhibition is still
      unclear. Here, we show that the inositol-1,4,5-trisphosphate receptor-associated
      cGMP kinase substrate (IRAG) is abundantly expressed in platelets and assembled
      in a macrocomplex together with cGKIbeta and the inositol-1,4,5-trisphosphate
      receptor type I (InsP3RI). cGKI phosphorylates IRAG at Ser664 and Ser677 in
      intact platelets. Targeted deletion of the IRAG-InsP3RI interaction in
      IRAGDelta12/Delta12 mutant mice leads to a loss of NO/cGMP-dependent inhibition
      of fibrinogen-receptor activation and platelet aggregation. Intracellular calcium
      transients were not affected by DEA/NO or cGMP in mutant platelets. Furthermore,
      intravital microscopy shows that NO fails to prevent arterial thrombosis of the
      injured carotid artery in IRAGDelta12/Delta12 mutants. These findings reveal that
      interaction between IRAG and InsP3RI has a central role in NO/cGMP-dependent
      inhibition of platelet aggregation and in vivo thrombosis.

PMID- 16990612
TI  - How many transcription factors does it take to turn on the heme oxygenase-1 gene?
AB  - The ability to communicate with the environment and respond to changes-
      particularly those of an adverse nature--within that environment is critical for
      cell function and survival. A key component of the overall cellular stress
      response includes adjustments in the gene expression program in favor of proteins
      that manifest activities capable of frustrating and eventually eliminating the
      molecular constituents of the stress condition. One protein providing such
      cytoprotective activity is heme oxygenase-1 (HO-1), an enzyme that catalyzes the
      rate-limiting reaction in heme catabolism (i.e., the oxidative cleavage of b-type
      heme molecules to yield equimolar quantities of biliverdin IXalpha, carbon
      monoxide, and iron). Because of the potent antioxidant, anti-inflammatory, and
      signaling properties of the reaction products, the HO-1 gene (hmox1) is
      frequently activated under a variety of cellular stress conditions. Cells use
      multiple signaling pathways and transcription factors to fine-tune their response
      to a specific circumstance. Among these factors, members of the heat-shock
      factor, nuclear factor-kappaB, nuclear factor-erythroid 2, and activator protein
      1 families are arguably the most important regulators of the cellular stress
      response in vertebrates. Although there is functional overlap between individual
      families, each broadly regulates different aspects of the cellular stress
      response and thus, with some exceptions, modulates the expression of different
      sets of targets genes. To the best of our knowledge, hmox1 is unique in that it
      is proposed to be directly regulated by all four of these stress-responsive
      transcription factors. In this article we provide a review and analysis of the
      data supporting this proposition.

PMID- 16990613
TI  - Lipid mediators as agonists for the resolution of acute lung inflammation and
      injury.
AB  - Resolution of acute lung inflammation and injury is an active process; it is not
      merely the absence of proinflammatory signals. Restoration of homeostasis is
      coordinated by specific mediators and cellular events. In response to injury and
      inflammatory stimuli, infiltrating leukocytes and tissue-resident cells interact
      to generate lipoxins (LXs), which are bioactive eicosanoids derived from
      arachidonic acid. In contrast to proinflammatory leukotrienes and prostaglandins,
      LXs display potent antiinflammatory actions. LXA(4) interacts with a G protein
      coupled receptor, termed ALX, that transduces counter-regulatory signals in part
      via intracellular polyisoprenyl phosphate remodeling. Presqualene diphosphate
      (PSDP) is a polyisoprenyl phosphate in human neutrophils that is rapidly
      converted to presqualene monophosphate (PSMP) upon cell activation. PSDP, but not
      PSMP, directly inhibits phospholipase D, phosphoinositol-3 kinase, and superoxide
      anion generation. LXs block PSDP turnover in neutrophil membranes to prevent
      proinflammatory responses. Hence, LX and polyisoprenyl phosphate signaling
      provide a counter-regulatory circuit to promote resolution of acute lung
      inflammation. LXA(4) and PSDP mimetics have been prepared with potent protective
      actions in murine models of asthma and acute lung injury.

PMID- 16990614
TI  - Epithelial cell apoptosis by fas ligand-positive myofibroblasts in lung fibrosis.
AB  - The Fas/Fas ligand (FasL) apoptotic pathway has been shown to be involved in
      bleomycin-induced lung fibrosis. We examined the hypothesis that myofibroblasts
      from fibrotic lungs possess a cytotoxic phenotype that causes apoptosis of
      epithelial cells via the Fas/FasL pathway. We show in vivo epithelial cell
      apoptosis and associated upregulation of Fas and apoptotic Fas pathway genes in
      epithelial cells of lungs with bleomycin-induced fibrosis. In addition, we show
      that FasL surface molecules are overexpressed on alpha-SMA-positive cells in mice
      with bleomycin-induced fibrosis, and in humans with idiopathic pulmonary
      fibrosis. This enables the molecules to kill Fas-positive epithelial cells. In
      contrast, FasL-deficient myofibroblasts lose this myofibroblast cytotoxic
      phenotype, both in vivo and in vitro. In vivo, there was no bleomycin-induced
      epithelial cell apoptosis, as assessed by specific M30 staining in chimeric FasL
      deficient mice that lacked FasL-positive myofibroblasts. In vitro, FasL-positive,
      but not FasL-negative myofibroblasts, induce mouse lung epithelial cell
      apoptosis. Thus myofibroblast cytotoxicity may underlie the absence of re
      epithelialization, resulting in persistent lung fibrosis.

PMID- 16990615
TI  - Induced trefoil factor family 1 expression by trans-differentiating Clara cells
      in a murine asthma model.
AB  - Asthma is a chronic inflammatory disease of the airways that is accompanied by
      goblet cell metaplasia and mucus hypersecretion. Trefoil factor family (TFF)
      peptides represent major secretory products of the respiratory tract and are
      synthesized together with mucins. In the murine lung, TFF2 is mainly expressed,
      whereas TFF1 transcripts represent only a minor species. TFF peptides are well
      known for their motogenic and anti-apoptotic effects, and they modulate the
      inflammatory response of bronchial epithelial cells. Here, an established mouse
      model of asthma was investigated (i.e., exposure to Aspergillus fumigatus [AF]
      antigens). RT-PCR analysis of lung tissue showed elevated levels particularly of
      TFF1 transcripts in AF-sensitized/challenged animals. In contrast, transcripts
      encoding Clara cell secretory protein (CCSP/CC10) were strongly diminished in
      these animals. For comparison, the expression of the goblet cell secretory
      granule marker mCLCA3/Gob-5, the mucins Muc1-Muc6 and Muc19, and the
      secretoglobins ScgB3A1 and ScgB3A2, as well as the mammalian ependymin-related
      gene MERP2, were monitored. Immunohistochemistry localized TFF1 mainly in cells
      with a mixed phenotype (e.g., TFF1-positive cells stain with the lectin wheat
      germ agglutinin (WGA), which recognizes mucins characteristic of goblet cells).
      In addition, these cells express CCSP/CC10, a Clara cell marker. When compared
      with mucins or CCSP/CC10, TFF1 was stored in a different population of secretory
      granules localized at the more basolateral portion of these cells. Thus, the
      results presented indicate for the first time that allergen exposure leads to the
      trans-differentiation of Clara cells toward a TFF1-expressing mucous phenotype.

PMID- 16990616
TI  - Anti-inflammatory activity of inhaled IL-4 receptor-alpha antisense
      oligonucleotide in mice.
AB  - The Th2 cytokines IL-4 and IL-13 mediate allergic pulmonary inflammation and
      airways hyperreactivity (AHR) in asthma models through signaling dependent upon
      the IL-4 receptor-alpha chain (IL-4Ralpha). IL-13 has been further implicated in
      the overproduction of mucus by the airway epithelium and in lung remodeling that
      commonly accompanies chronic inflammation. IL-4Ralpha-deficient mice are
      resistant to allergen-induced asthma, highlighting the therapeutic promise of
      selective molecular inhibitors of IL-4Ralpha. We designed a chemically modified
      IL-4Ralpha antisense oligonucleotide (IL-4Ralpha ASO) that specifically inhibits
      IL-4Ralpha protein expression in lung eosinophils, macrophages, dendritic cells,
      and airway epithelium after inhalation in allergen-challenged mice. Inhalation of
      IL-4Ralpha ASO attenuated allergen-induced AHR, suppressed airway eosinophilia
      and neutrophilia, and inhibited production of airway Th2 cytokines and chemokines
      in previously allergen-primed and -challenged mice. Histologic analysis of lungs
      from these animals demonstrated reduced goblet cell metaplasia and mucus staining
      that correlated with inhibition of Muc5AC gene expression in lung tissue.
      Therapeutic administration of inhaled IL-4Ralpha ASO in chronically allergen
      challenged mice produced a spectrum of anti-inflammatory activity similar to that
      of systemically administered Dexamethasone with the added benefit of reduced
      airway neutrophilia. These data support the potential utility of a dual IL-4 and
      IL-13 oligonucleotide inhibitor in allergy/asthma, and suggest that local
      inhibition of IL-4Ralpha in the lung is sufficient to suppress allergen-induced
      pulmonary inflammation and AHR.

PMID- 16990618
TI  - Oncology practices recruit pharmacists for efficiency, savings.

PMID- 16990619
TI  - Telepharmacy project aids North Dakota's rural communities.

PMID- 16990620
TI  - Uninsured numbers keep climbing.

PMID- 16990622
TI  - Advice for residency candidates going to the Midyear Clinical Meeting.

PMID- 16990623
TI  - The pharmacist's role in teaching methotrexate injection for patients with
      Crohn's disease.

PMID- 16990624
TI  - Family medicine pharmacy residency programs.

PMID- 16990625
TI  - Establishing a Web-based program for reimbursement for medication therapy
      management services.

PMID- 16990627
TI  - Echinocandins in the management of invasive fungal infections, Part 2.
AB  - PURPOSE: The chemistry, pharmacology, spectrum of activity, resistance,
      pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, drug
      interactions, dosage and administration, cost, and place in therapy of
      echinocandins are reviewed. SUMMARY: Three echinocandins are currently available:
      caspofungin, micafungin, and anidulafungin. The principal mechanism of action of
      the echinocandins is the noncompetitive inhibition of beta-(1,3)-D-glucan
      synthase, an essential component of the cell wall of many fungi that is not
      present in mammalian cells. Echinocandins exhibit fungicidal activity against
      Candida species, including triazole-resistant isolates, and fungistatic activity
      against Aspergillus species. While fungistatic against mold, echinocandins may
      hold promise for the treatment of these pathogens when given in combination with
      amphotericin B or broad-spectrum triazoles, such as voriconazole. To date,
      resistance to echinocandins has been reported in only two patients. Echinocandins
      exhibit concentration-dependent activity against Candida species. In clinical
      trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal
      candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as
      antifungal prophylaxis in hematopoietic stem cell transplant recipients and in
      the treatment of esophageal candidiasis. Anidulafungin received approved labeling
      from the Food and Drug Administration in February 2006. Clinical efficacy data
      will be forthcoming. CONCLUSION: Echinocandins are fungicidal against yeast and
      fungistatic against mold. Their limited toxicity profile and minimal drug-drug
      interactions make them an attractive new option for the treatment of invasive
      fungal infections. Their cost may limit their use as initial therapy for patients
      with fungemia in medical centers or intensive care units with a high rate of
      triazoleresistant Candida infections.

PMID- 16990628
TI  - Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen
      poisoning.
AB  - PURPOSE: The efficacy, safety, and cost issues that should be considered when
      deciding on the appropriate route of acetylcysteine for the treatment of patients
      with acetaminophen poisoning are reviewed. SUMMARY: Oral and i.v. acetylcysteine
      appear to be equally effective when given within 8-10 hours of acetaminophen
      overdose. Anaphylactoid reactions to i.v. acetylcysteine have generally been
      reported in 3-6% of acetaminophen-poisoned patients. Dosing errors and
      hyponatremia have occurred in pediatric patients receiving i.v. acetylcysteine.
      Several investigators found an increased rate of anaphylactoid reactions in
      patients treated with i.v. acetylcysteine whose pretreatment serum acetaminophen
      levels were nontoxic. Compounding i.v. acetylcysteine from the oral preparation
      is less expensive than using premade i.v. solution. State pharmacy laws dictate
      whether extemporaneous compounding of acetylcysteine from the oral formulation is
      allowed. Oral acetylcysteine administration has resulted in minimal anaphylactoid
      reactions and is safer than i.v. acetylcysteine. Oral therapy should
      preferentially be considered in patients with asthma or atopic histories. The
      most important factors to consider when selecting the route of acetylcysteine
      administration include individual susceptibility, the severity of acetaminophen
      toxicity, and the time interval between acetaminophen ingestion and initiation of
      acetylcysteine therapy. CONCLUSION: Oral acetylcysteine administered within 8-10
      hours of acetaminophen overdose prevents liver toxicity in the majority of
      patients who tolerate it and have no contraindications to therapy. I.V.
      acetylcysteine should be administered when patients are treated more than 10
      hours postingestion of acetaminophen overdose or have underlying conditions
      preventing oral treatment. Anaphylactoid reactions are rare and occur more
      frequently in patients treated with the i.v. preparation.

PMID- 16990629
TI  - Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers.
AB  - PURPOSE: The toxic effects and treatment of beta-adrenergic blocker and calcium
      channel blocker (CCB) overdose are reviewed. SUMMARY: Overdoses with
      cardiovascular drugs are associated with significant morbidity and mortality.
      Beta-blockers and CCBs represent the most important classes of cardiovascular
      drugs. In overdose, beta-blockers and CCBs have similar presentation and
      treatment overlaps and are often refractory to standard resuscitation measures.
      The common feature of beta-blocker toxicity is excessive blockade of the beta
      receptors resulting in bradycardia and hypotension. Poisoning by CCBs is
      characterized by cardiovascular toxicity with hypotension and conduction
      disturbances, including sinus bradycardia and varying degrees of atrioventricular
      block. Therapies include beta-agonists, glucagon, and phosphodiesterase
      inhibitors. However, in beta-blocker poisoning where symptomatic bradycardia and
      hypotension are present, high-dose glucagon is considered the first-line
      antidote. Traditionally, antidotes for CCB overdose have included calcium,
      glucagon, adrenergic drugs, and amrinone. For cases of CCB poisoning where
      cardiotoxicity is evident, first-line therapy is a combination of calcium and
      epinephrine; high-dose insulin with supplemental dextrose and potassium therapy
      (HDIDK) is reserved for refractory cases. Health-system pharmacists should be
      aware that when these drugs are used as antidotes, higher than normal dosing is
      needed. CONCLUSION: Poisoning by beta-blockers or CCBs usually produces
      hypotension and bradycardia, which may be refractory to standard resuscitation
      measures. For cases of beta-blocker poisoning where symptomatic bradycardia and
      hypotension are present, high-dose glucagon is considered the first-line
      antidote. For cases of CCB poisoning where cardiotoxicity is evident, a
      combination of calcium and epinephrine should be used initially, reserving HDIDK
      for refractory cases.

PMID- 16990630
TI  - Risks versus benefits of cyclooxygenase-2-selective nonsteroidal antiinflammatory
      drugs.
AB  - PURPOSE: A summary of the basic science underlying the current controversies
      regarding cyclooxygenase-2 (COX-2)-selective nonsteroidal antiinflammatory drugs
      (NSAIDs), including data on their cardiovascular safety, their gastrointestinal
      (GI) benefits, cost-effectiveness, physician-prescribing trends, and
      recommendations for prescribing these agents is presented. SUMMARY: A number of
      randomized controlled trials (RCTs) have reported that COX-2-selective NSAIDs
      increase cardiovascular events, although there appear to be gradations of risks
      among the COX-2-selective NSAIDs. In addition, traditional NSAIDs may increase
      the risk for cardiovascular events, complicating the interpretation of RCTs that
      use traditional NSAIDs as comparators. Selective inhibitors of COX-2-selective
      NSAIDs are effective antiinflammatory and analgesic drugs with improved upper-GI
      safety compared to traditional NSAIDs. Data on the cost-effectiveness of COX-2
      selective NSAIDs indicate that they should be limited to patients at high risk
      for upper-GI adverse effects. However, they had been increasingly used in
      patients with lower GI risks until recent events reversed that trend.
      Circumstances under which COX-2-selective NSAIDs may be appropriate are in
      patients at high GI risk and in patients who did not respond to multiple
      traditional NSAIDs. The national spotlight in the United States on NSAID-related
      adverse events and recent lawsuits against health care providers prescribing COX
      2-selective NSAIDs further highlights the need for provider-patient communication
      and risk disclosure. The relative cardiovascular risks of NSAIDs are similar in
      magnitude to other currently prescribed therapies. CONCLUSION: Health care
      providers must consider the efficacy, GI and cardiovascular risks, concomitant
      medications, and costs when determining the appropriateness of COX-2-selective
      NSAID therapy.

PMID- 16990631
TI  - Medication and nutrient administration considerations after bariatric surgery.
AB  - PURPOSE: Medication and nutrient administration considerations after bariatric
      surgery are discussed. SUMMARY: Bariatric surgery is categorized by surgical
      technique (i.e., restrictive procedure or a combination of restrictive and
      malabsorptive procedures). Roux-en-Y gastric bypass is the most frequently
      performed bariatric surgery in the United States. Patients who have undergone
      this surgery are at risk for nutrient deficiencies. Several factors, such as pH
      and absorption sites, should be considered when providing these patients with
      appropriate supplementation. Drug solubility and surface area for absorption are
      also affected by gastric bypass procedures. By bypassing major portions of the
      small intestine, Roux-en-Y procedures drastically reduce the surface area for
      absorption. These changes may warrant manipulation in drug route or dose to
      ensure adequate delivery. Drugs with long absorptive phases that remain in the
      intestine for extended periods are likely to exhibit decreased bioavailability in
      these patients. The reduced size of the stomach after surgery can place patients
      at risk for adverse events associated with some medications. Medications
      implicated in such adverse events include nonsteroidal antiinflammatory drugs,
      salicylates, and oral bisphosphonates. Drugs that are rapidly and primarily
      absorbed in the stomach or duodenum are likely to exhibit decreased absorption in
      patients who have had combination restrictive-malabsorptive procedures. Because
      reduced drug absorption may result in decreased efficacy rather than toxicity,
      increased patient monitoring for therapeutic effects can help detect potential
      absorption problems. CONCLUSION: Selection of appropriate nutrient salts can
      improve nutrient replacement in patients who have undergone bariatric surgery.
      Changes in dosage forms based on drug characteristics can improve
      bioavailability.

PMID- 16990632
TI  - Acute renal failure associated with inhaled tobramycin.
AB  - PURPOSE: A case of nephrotoxicity possibly caused by tobramycin inhalation
      solution is presented. SUMMARY: A 62-year-old Caucasian woman was admitted for
      treatment of decreased urine output and sepsis secondary to Pseudomonas
      aeruginosa. Her past medical history was significant for multiple diseases,
      including chronic renal insufficiency (baseline serum creatinine concentration
      [SCr] 2 mg/dL). One month postadmission, the patient was diagnosed with health
      care-associated pneumonia. The patient was initiated on piperacillin-tazobactam
      and tobramycin 2 mg/kg i.v. She was changed to imipenem-cilastatin with
      continuation of i.v. tobramycin. A month after discontinuation of her antibiotic
      regimen, the patient was diagnosed with P. aeruginosa pneumonia. The patient
      received imipenem-cilastatin, vancomycin, and inhaled tobramycin 300 mg twice
      daily. At that time, her SCr was 2 mg/dL. Inhaled tobramycin was continued for
      four weeks, and the patient's SCr steadily rose to a peak of 4.5 mg/dL. During
      week 1 of treatment, multidrug-resistant P. aeruginosa and methicillin-resistant
      Staphylococcus aureus were diagnosed. The patient continued to receive i.v.
      imipenem-cilastatin, vancomycin, and inhaled tobramycin with an SCr of 1.9 mg/dL.
      However, at the end of week 2, the patient's SCr began to slowly rise (2.3
      mg/dL). At week 3, imipenem-cilastatin was discontinued; inhaled tobramycin was
      continued. The patient's SCr continued to rise (3.2 mg/dL). At week 4, her SCr
      rose to 4.5 mg/dL, resulting in initiation of hemodialysis and discontinuation of
      inhaled tobramycin. The patient's SCr never returned to baseline, and renal
      function was never regained. CONCLUSION: Acute renal failure requiring dialysis
      occurred in a high-risk patient receiving an extended course of treatment with
      inhaled tobramycin.

PMID- 16990633
TI  - Effect of switching medically vulnerable patients with uncontrolled diabetes from
      isophane insulin human to insulin glargine.
AB  - PURPOSE: The purpose of this observational study was to determine if switching
      from isophane insulin human (NPH) to insulin glargine would improve glycemic
      control in a medically vulnerable population with uncontrolled diabetes. METHODS:
      A retrospective cohort review of patients' medical records was performed that
      recorded events occurring between January 1, 2001, and December 31, 2003. The
      cohort consisted of patients with diabetes in an adult medicine clinic at a
      county hospital. Patients were included if they were receiving NPH insulin for a
      minimum of six months and subsequently switched to insulin glargine for a minimum
      of six months. RESULTS: The study included 43 patients. There was no significant
      difference in mean glycosylated hemoglobin (HbA(1c)) between NPH insulin (9.6%)
      and insulin glargine (9.7%) regimens (p = 0.78, 95% confidence interval, -0.62%,
      0.82%). Neither was there a significant difference in the frequency or severity
      of hypoglycemic episodes between the two treatments. Patients experienced
      significantly fewer diabetes-associated visits over six months while on insulin
      glargine. Refill frequency did not differ significantly when patients were
      receiving NPH insulin versus insulin glargine. When analyzing patient
      characteristics, those of Hispanic ethnicity experienced HbA(1c) values
      significantly higher than white patients. Several characteristics were associated
      with refill frequency. CONCLUSION: The results of our study indicate that both
      NPH- and glargine-based basal insulin regimens result in similar levels of
      glycemic control in a medically vulnerable population with diabetes, without
      significant differences in the number or severity of hypoglycemic episodes or in
      refill frequency.

PMID- 16990634
TI  - Comparing two predictive methods for determining serum vancomycin concentrations
      at a Veterans Affairs Medical Center.
AB  - PURPOSE: Two predictive methods for determining serum vancomycin concentrations
      (SVCs) at a Veterans Affairs medical center were compared. METHODS: The data for
      inpatients at the San Francisco Veterans Affairs Medical Center who received i.v.
      vancomycin and had vancomycin concentrations recorded in 2003 were included in
      this retrospective study. Creatinine clearance was estimated by the Cockcroft and
      Gault equation. Volume of distribution and creatinine clearance were calculated
      for each patient, using the Leonard and Boro method and the Rushing and Ambrose
      method. The Sheiner and Beal method for determining precision and bias was used
      to evaluate whether the two methods significantly differed in their ability to
      predict SVCs. RESULTS: Of the 223 patients identified, 122 patients were
      included, and 212 SVCs were analyzed. The population was mostly male and had a
      mean age of 64.1 years. There were no significant differences in 95% confidence
      intervals for relative precision and relative bias between the two methods. In
      patients whose weight was within 120% of their ideal body weight (IBW), the
      Leonard and Boro method was significantly more precise and less biased in
      predicting SVCs. In patients whose weight exceeded 120% of their IBW, the Rushing
      and Ambrose method was less biased and tended to be more precise, although the
      difference in precision was not significant. CONCLUSION: Both methods yielded
      similar predictability for SVCs in a veterans population. The Leonard and Boro
      method better predicted SVCs in patients weighing within 120% of their IBW, while
      the Rushing and Ambrose method appeared to be more appropriate for calculating
      vancomycin dosages in patients whose weight exceeded 120% of their IBW.

PMID- 16990635
TI  - Adverse-drug-event rates for high-cost and high-use drugs in the intensive care
      unit.
AB  - PURPOSE: The rates of adverse drug events (ADEs) associated with high-cost and
      high-use drugs in the intensive care unit (ICU) were studied. METHODS: This
      retrospective analysis was conducted from October 1997 through June 2001 in a 647
      bed academic medical center with over 120 ICU beds. Adult patients with a
      documented ADE occurring in the ICU were included in the analysis. ADE
      information, including suspected medication, causality, preventability, and
      severity, was extracted from the institutional ADE database. Published
      definitions of ADEs and published scales for causality and severity assessments
      were used. High-cost medications were those in the top 50% of cumulative ICU
      medication costs, and high-use medications accounted for the upper 50% of all
      medications used in the ICU. Between-group comparisons of ADE rates,
      preventability, and severity associated with high-cost and high-use medications
      were conducted. RESULTS: Of the 17 medications that were considered high cost, 9
      (53%) were associated with ADEs. Of the 15 medications that met the criteria for
      high-use drugs, 12 (80%) were associated with ADEs. The rates of ADEs associated
      with high-cost and high-use drugs did not significantly differ (43% versus 75%,
      respectively; p = 0.098). ADEs associated with high-cost and high-use medications
      were categorized as mild (15% versus 10%, respectively), moderate (52% versus
      50%, respectively), and severe (33% versus 40%, respectively) (p > 0.05).
      CONCLUSION: The frequency, severity, and preventability of ADEs in the ICU were
      not associated with a drug's cost or frequency of use. Monitoring priorities of
      the critical care pharmacist should not be dictated by cost alone but should
      include frequency of use and the potential for causing an ADE.

PMID- 16990636
TI  - Delivery of esomeprazole magnesium through nasogastric and gastrostomy tubes
      using an oral liquid vehicle as a suspending agent in vitro.
AB  - PURPOSE: The optimal delivery medium for esomeprazole magnesium enteric-coated
      pellets dispersed in various concentrations of Ora-Plus suspension through
      commonly used nasogastric and gastrostomy tubes using a previously used
      standardized in vitro protocol was studied. METHODS: The study was conducted in
      two phases. In phase A, 60 size 14 French nasogastric tubes were used to compare
      esomeprazole pellet delivery via tap water or 30, 50, or 70% Ora-Plus
      concentrations (15 tubes for each). In phase B, tap water and the concentration
      that yielded the best pellet delivery from phase A were used with the narrower
      size 8 and shorter size 20 French tubes. In both phases, the appropriate volume
      of water was added. All capsules were assumed to have 1,240 pellets. At the end
      of each administration, pellet retention counts were performed. RESULTS: The
      results showed excellent delivery of esomeprazole pellets using water as a medium
      for tube delivery. When compared with tap water as a delivery medium, no
      differences in pellet retention were observed when 30% and 50% Ora-Plus were
      used; thus, these Ora-Plus concentrations are feasible alternatives to tap water
      for nasogastric tube delivery of esomeprazole pellets. CONCLUSION: Administration
      of esomeprazole magnesium enteric-coated pellets dispersed in tap water or Ora
      Plus through size 14 French nasogastric tubes in vitro delivered over 99% of
      capsule contents, regardless of the Ora-Plus concentration used. For immediate
      bedside administration, Ora-Plus at 50% concentration is a feasible alternative
      to water when delivering the pellets through size 14 French tubes, while 30% Ora
      Plus is an alternative to water for all tubes studied.

PMID- 16990637
TI  - How to write a patient case report.
AB  - PURPOSE: Guidelines for writing patient case reports, with a focus on medication
      related reports, are provided. SUMMARY: The format of a patient case report
      encompasses the following five sections: an abstract, an introduction and
      objective that contain a literature review, a description of the case report, a
      discussion that includes a detailed explanation of the literature review, a
      summary of the case, and a conclusion. The abstract of a patient case report
      should succinctly include the four sections of the main text of the report. The
      introduction section should provide the subject, purpose, and merit of the case
      report. It must explain why the case report is novel or merits review, and it
      should include a comprehensive literature review that corroborates the author's
      claims. The case presentation section should describe the case in chronological
      order and in enough detail for the reader to establish his or her own conclusions
      about the case's validity. The discussion section is the most important section
      of the case report. It ought to evaluate the patient case for accuracy, validity,
      and uniqueness; compare and contrast the case report with the published
      literature; derive new knowledge; summarize the essential features of the report;
      and draw recommendations. The conclusion section should be brief and provide a
      conclusion with evidence-based recommendations and applicability to practice.
      CONCLUSION: Patient case reports are valuable resources of new and unusual
      information that may lead to vital research.

PMID- 16990638
TI  - Ruminations on Ecclesiasticus.

PMID- 16990639
TI  - Prevention of cytomegalovirus disease in solid organ transplant patients:
      prophylactic versus preemptive therapy.
AB  - PURPOSE: The advantages and disadvantages of universal prophylaxis and preemptive
      therapy and current evidence-based recommendations for preventing cytomegalovirus
      (CMV) disease in solid organ transplant recipients are discussed. SUMMARY:
      Advantages of universal prophylaxis include the ease of implementation, a reduced
      incidence of CMV disease, and possibly fewer indirect effects of CMV infection.
      Disadvantages of universal prophylaxis may include prolonged antiviral drug
      exposure, resistance, toxicity, the development of late-onset CMV disease, and
      greater drug costs. Advantages of preemptive therapy may include reduced drug
      exposure and decreased risk for toxicity and resistance. Disadvantages include
      the logistic demands of laboratory testing, uncertainty about the impact on the
      indirect effects of CMV disease, and the costs associated with failure to prevent
      CMV disease. Evidence-based guidelines call for universal prophylaxis for
      patients at highest risk for CMV disease. Preemptive therapy may be most
      appropriate for those at a moderate or low risk of CMV. Antiviral drug regimens
      used for universal prophylaxis depend on the type of organ transplanted and the
      donor-recipient CMV serostatus. The optimal preemptive drug regimen and
      laboratory monitoring strategy are unknown. CONCLUSION: Selection of a strategy
      for preventing CMV disease in solid organ transplant patients requires
      consideration of patient-specific risk factors as well as practical
      considerations, such as available resources.

PMID- 16990640
TI  - Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid
      organ transplant recipients.
AB  - PURPOSE: The implications of the findings from clinical studies and
      pharmacokinetic analyses of the antiviral agent valganciclovir for dosing of the
      drug to prevent cytomegalovirus (CMV) disease in solid organ transplant
      recipients are reviewed. SUMMARY: Valganciclovir, an oral prodrug of ganciclovir,
      is as effective as oral ganciclovir for preventing CMV disease, although
      prophylaxis with either agent may delay CMV disease. Dosage reduction is required
      for both drugs in patients with renal impairment to prevent high plasma
      ganciclovir concentrations and toxicity. A valganciclovir dosage of 900 mg/day is
      required in patients with normal renal function, especially those at high risk
      for CMV disease, to provide adequate systemic ganciclovir exposure. Some studies
      suggest that a lower dosage might suffice for patients at a low risk for CMV
      disease. CONCLUSION: Valganciclovir dosing should be based on renal function to
      avoid toxicity.

PMID- 16990641
TI  - Current status of the prevention of cytomegalovirus disease in solid organ
      transplant recipients. Introduction.

PMID- 16990643
TI  - Etiology and impact of cytomegalovirus disease on solid organ transplant
      recipients.
AB  - PURPOSE: The characteristics, etiology, natural history, and direct and indirect
      effects of CMV disease in solid organ transplant recipients are described.
      SUMMARY: CMV is a common herpesvirus that may be present in the donor or
      recipient of a solid organ transplant. Even though it is rarely pathogenic in
      healthy patients, transplant recipients are at risk for CMV viremia and
      symptomatic disease due to their immune-suppressed status. In addition to
      symptoms directly attributed to active disease, CMV can have a variety of
      indirect effects. Indirect effects may include additional infectious
      complications, posttransplant lymphoproliferative disease, allograft rejection,
      allograft loss, or death. The three most prevalent risk factors for CMV infection
      are CMV seronegativity in a recipient of an organ from a CMV-seropositive donor,
      the type of organ transplanted, and the degree of immune suppression. CMV
      prophylaxis is effective at preventing disease, but may result in a delayed onset
      where CMV disease occurs once the prophylaxis is stopped. CONCLUSION: Knowledge
      of risk factors for CMV infection and disease, the natural history in transplant
      recipients, and its direct and indirect effects will help clinicians make
      appropriate decisions regarding the use of preventive strategies.

PMID- 16990644
TI  - Ceramide structural features required to stimulate ABCA1-mediated cholesterol
      efflux to apolipoprotein A-I.
AB  - Ceramide is a component of the sphingomyelin cycle and a well-established lipid
      signaling molecule. We recently reported that ceramide specifically increased
      ABCA1-mediated cholesterol efflux to apolipoprotein A-I (apoA-I), a critical
      process that leads to the formation of cardioprotective HDL. In this report, we
      characterize the structural features of ceramide required for this effect. C2
      dihydroceramide, which contains a fully saturated acyl chain and is commonly used
      as a negative control for ceramide apoptotic signaling, stimulated a 2- to 5-fold
      increase in ABCA1-mediated cholesterol efflux to apoA-I over a 0-60 muM
      concentration range without the cell toxicity apparent with native C2 ceramide.
      Compared with C2 ceramide, C6 and C8 ceramides with medium-length N-acyl chains
      showed a similar extent of efflux stimulation (a 2- to 5-fold increase) but at a
      higher onset concentration than the less hydrophobic C2 ceramide. In contrast,
      the reduced and methylated ceramide analogs, N,N-dimethyl sphingosine and N,N,N
      trimethyl sphingosine, failed to stimulate cholesterol efflux. We found that
      changes in the native spatial orientation at either of two chiral carbon centers
      (or both) resulted in an approximately 50% decrease compared with native ceramide
      stimulated cholesterol efflux. These data show that the overall ceramide shape
      and the amide bond are critical for the cholesterol efflux effect and suggest
      that ceramide acts through a protein-mediated pathway to affect ABCA1 activity.

PMID- 16990645
TI  - Modeling the structure of the StART domains of MLN64 and StAR proteins in complex
      with cholesterol.
AB  - Steroidogenic acute regulatory protein-related lipid transfer (StART) domains are
      ubiquitously involved in intracellular lipid transport and metabolism and other
      cell-signaling events. In this work, we use a flexible docking algorithm,
      comparative modeling, and molecular dynamics (MD) simulations to generate
      plausible three-dimensional atomic models of the StART domains of human
      metastatic lymph node 64 (MLN64) and steroidogenic acute regulatory protein
      (StAR) proteins in complex with cholesterol. Our results show that cholesterol
      can adopt a similar conformation in the binding cavity in both cases and that the
      main contribution to the protein-ligand interaction energy derives from
      hydrophobic contacts. However, hydrogen-bonding and water-mediated interactions
      appear to be important in the fine-tuning of the binding affinity and the
      position of the ligand. To gain insights into the mechanism of binding, we
      carried out steered MD simulations in which cholesterol was gradually extracted
      from within the StAR model. These simulations indicate that a transient opening
      of loop Omega1 may be sufficient for uptake and release, and they also reveal a
      pathway of intermediate states involving residues known to be crucial for StAR
      activity. Based on these observations, we suggest specific mutagenesis targets
      for binding studies of cholesterol and its derivatives that could improve our
      understanding of the structural determinants for ligand binding by sterol carrier
      proteins.

PMID- 16990646
TI  - Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in
      plasma and impairs their catabolism.
AB  - Postprandial hypertriglyceridemia and low plasma HDL levels, which are principal
      features of the metabolic syndrome, are displayed by transgenic mice expressing
      human apolipoprotein A-II (hapoA-II). In these mice, hypertriglyceridemia results
      from the inhibition of lipoprotein lipase and hepatic lipase activities by hapoA
      II carried on VLDL. This study aimed to determine whether the association of
      hapoA-II with triglyceride-rich lipoproteins (TRLs) is sufficient to impair their
      catabolism. To measure plasma TRL residence time, intestinal TRL production was
      induced by a radioactive oral lipid bolus. Radioactive and total triglyceride
      (TG) were rapidly cleared in control mice but accumulated in plasma of transgenic
      mice, in relation to hapoA-II concentration. Similar plasma TG accumulations were
      measured in transgenic mice with or without endogenous apoA-II expression. HapoA
      II (synthesized in liver) was detected in chylomicrons (produced by intestine).
      The association of hapoA-II with TRL in plasma was further confirmed by the
      absence of hapoA-II in chylomicrons and VLDL of transgenic mice injected with
      Triton WR 1339, which prevents apolipoprotein exchanges. We show that the
      association of hapoA-II with TRL occurs in the circulation and induces
      postprandial hypertriglyceridemia.

PMID- 16990647
TI  - Abstracts from the 11th Annual Meeting of the ECCR (European Council for
      Cardiovascular Research), Nice, France, 29 September-1 October 2006.

PMID- 16990648
TI  - Detection of chronic kidney disease in patients with or at increased risk of
      cardiovascular disease: a science advisory from the American Heart Association
      Kidney and Cardiovascular Disease Council; the Councils on High Blood Pressure
      Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention;
      and the Quality of Care and Outcomes Research Interdisciplinary Working Group:
      Developed in Collaboration With the National Kidney Foundation.
AB  - Chronic kidney disease (CKD) occurs commonly in patients with cardiovascular
      disease. In addition, CKD is a risk factor for the development and progression of
      cardiovascular disease. In this advisory, we present recommendations for the
      detection of CKD in patients with cardiovascular disease. CKD can be reliably
      detected with the combined use of the Modification of Diet in Renal Disease
      equation to estimate glomerular filtration rate and a sensitive test to detect
      microalbuminuria. All patients with cardiovascular disease should be screened for
      evidence of kidney disease with these two determinations.

PMID- 16990649
TI  - A perspective view of sodium iodide symporter research and its clinical
      implications.
AB  - The sodium iodide symporter (NIS) is an intrinsic plasma membrane protein that
      mediates active iodide transport into the thyroid gland and into several
      extrathyroidal tissues, in particular the lactating mammary gland. Cloning and
      molecular characterization of the NIS have allowed the investigation of its key
      role in thyroid physiology as well as its potential pathophysiological and
      therapeutic implications in benign and malignant thyroid diseases. Similarly,
      elucidating the mechanisms underlying the regulation of NIS in lactating mammary
      gland and breast cancer, in which more than 80% of cases express endogenous NIS,
      may lead to findings that have novel implications for pathophysiology and
      therapy. Two approaches may, in the future, pave the way to extend the use of
      radioiodide treatment to nonthyroidal cancer. One is based on the reinduction of
      endogenous NIS expression in thyroid and breast cancer by targeting the main
      mechanisms involving tumoral transformation and dedifferentiation. The other is
      based on the application of NIS as a novel cytoreductive gene therapy strategy.
      NIS offers the unique advantage that it can be used both as a reporter and as a
      therapeutic gene, so that it is possible to image, monitor, and treat the tumor
      with radioiodide, just as in differentiated thyroid cancer. This review
      summarizes the main recent findings in NIS research that have a direct impact on
      diagnosis and therapeutic management.

PMID- 16990650
TI  - Hypothalamic-pituitary-gonadal axis in two men with aromatase deficiency:
      evidence that circulating estrogens are required at the hypothalamic level for
      the integrity of gonadotropin negative feedback.
AB  - BACKGROUND: In men, the feedback of gonadotropins is regulated by estrogens that
      come from the aromatization of testosterone, but the relative contribution to the
      inhibition of LH and FSH secretion by the amount of locally produced estrogens
      within the hypothalamus and/or the pituitary, and the amount of circulating
      estrogens still remains unknown. OBJECTIVE: In order to evaluate the effect of
      regulation induced by estradiol on the hypothalamic-pituitary-gonadal (HPG) axis,
      we studied the pulsatility of LH and FSH in two aromatase-deficient men (called
      subject 1 and subject 2), in which the production rate of estrogen (both local
      and circulating) is completely, or at least severely, impaired. DESIGN: FSH and
      LH were evaluated in terms of their pulsated secretion and as GnRH-stimulated
      secretion in two phases: phase 1, before estrogen treatment; and phase 2, during
      estrogen treatment with 25 microg transdermal estradiol twice weekly. METHODS:
      Blood samples were taken during phase 1 and phase 2 at 0800 h for basal
      measurements of LH, FSH, inhibin B, testosterone, and estradiol. The analysis of
      the pulsatility of LH and FSH was performed by sampling every 10 min for 8 h in
      the two phases. Gonadotropin response to GnRH-stimulation test was studied by
      serial standard sampling after 100 microg GnRH i.v. bolus in phases 1 and 2.
      RESULTS: Estrogen treatment led to a significant reduction in both LH-pulsated
      frequency (7.5 +/- 0.7 in phase 1, 4.5 +/- 0.7 in phase 2) and amplitudes (3.5 +/
      0.006 in phase 1, 1.9 +/- 0.4 in phase 2) of peaks, whereas FSH showed only a
      conspicuous reduction in serum levels and a trend towards the reduction of the
      amplitudes of its peaks without modification of the frequency of the pulses. Both
      testosterone and gonadotropins decreased during phase 2, whereas estradiol
      reached the normal range in both subjects. Transdermal estradiol treatment
      significantly lowered the peaks of both serum LH and FSH after GnRH as well as
      the incremental area under the curve after GnRH administration in both subjects.
      Basal serum inhibin B levels were slightly higher before transdermal estradiol
      treatment (phase 1) than during estrogen treatment (phase 2) in both subjects.
      CONCLUSIONS: The administration of estrogen to aromatase-deficient men discloses
      the effects of circulating estrogens on LH secretion, exerted both at pituitary
      level, as shown by the decrease of basal and GnRH-stimulated secretion of LH and
      the LH pulsed amplitude, and at hypothalamic level as shown by the reduction of
      the frequency of LH pulses. The present study, coupling the outcomes of basal,
      GnRH-stimulated and the pulsatile evaluation of LH and FSH secretion in two
      aromatase-deficient men, demonstrates that circulating estrogens play an
      inhibitory role in LH secretion by acting on the hypothalamus and the pituitary
      gland of men. The discrepancy among testosterone levels, the arrest of
      spermatogenesis and a slightly inappropriate respective increase of serum FSH
      (lower than expected) suggests a possible role of estrogens in the priming and
      the maturation of HPG axis in men, an event that has never occurred in these two
      subjects as a consequence of chronic estrogen deprivation.

PMID- 16990651
TI  - Malignant prolactinoma: case report and review of the literature.
AB  - Pituitary carcinomas are extremely rare. In general, the initial clinical,
      biochemical, and histological characteristics are of minimal utility in
      distinguishing benign adenomas from pituitary carcinomas. We describe a 63-year
      old woman with a macroprolactinoma, who presented with diplopia and blurred
      vision. This unusual initial presentation and the subsequent aggressive clinical
      course, with diffuse local and distant intramedullary metastases, prompted us in
      retrospect to make a detailed analysis of the therapeutic interventions and
      histology. In addition, we reviewed all available literature on published cases
      of malignant prolactinoma and detailed their epidemiological, clinical, and
      histopathological characteristics. In brief, it is postulated that pituitary
      carcinomas arise from the transformation of initially large, but benign,
      adenomas. Unusual and/or atypical clinical manifestations appear to occur more
      frequently. In vivo, the development of dopamine agonist resistance in invasive
      macroprolactinoma is indicative of malignancy and should prompt the clinician to
      perform a biopsy of the tumor. For pituitary tumors that exhibit high mitotic
      activity, increased Ki-67 and/or p53 immunoreactivity, it may be useful to denote
      these tumors as 'atypical' prolactinomas to raise the possibility of future
      malignant development.

PMID- 16990652
TI  - Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid
      nodules in geographical regions with different iodine supply in Turkey.
AB  - OBJECTIVE: Differences in iodine intake could account for the variable
      prevalences reported for somatic TSH receptor (TSHR) mutations in toxic thyroid
      nodules (TTNs). However, this question has not been settled, since no study has
      yet determined the TSHR mutation prevalence in regions with different iodine
      supplies in the same population using the same methodology. Therefore, we studied
      the prevalence of somatic TSHR mutations in TTNs from patients living in iodine
      deficient or -sufficient regions in Turkey. DESIGN AND METHODS: We screened 74
      TTNs for somatic TSHR mutations. Exons 9 and 10 of the TSHR and 7 and 8 of the
      Gsalpha were screened by denaturing gradient gel electrophoresis. Determination
      of X-chromosome inactivation was used for clonality analysis. RESULTS: TSHR
      mutations were identified in 52 (70.2%) of 74 TTNs. A Gsalpha mutation was
      identified in one TTN. Three new TSHR mutations were detected (A627V, I640K,
      I486N). No significant difference between frequencies of TSHR mutations in iodine
      deficient/sufficient regions was found. The frequency of non-random X-chromosome
      inactivation was similar in iodine-sufficient or -deficient regions and in TSHR
      mutation positive or negative hot nodules. CONCLUSIONS: These findings suggest
      that TTNs in iodine deficient/sufficient areas predominantly arise from aberrant
      growth of a single cell. Our results suggest that neither the prevalence of TSHR
      mutations nor that of monoclonal TTNs is related to iodine supply.

PMID- 16990653
TI  - The association between hypoechogenicity or irregular echo pattern at thyroid
      ultrasonography and thyroid function in the general population.
AB  - OBJECTIVE: Patients with overt hypothyroidism show decreased echogenicity of the
      thyroid at ultrasonography (US). The aim of this study was to investigate the
      association between echogenicity of the thyroid/irregular echo pattern, and
      thyroid function in the general population, i.e. subjects without overt thyroid
      disease. DESIGN: A cross-sectional investigation of 4649 randomly selected adult
      subjects. METHODS: Blood samples were analysed for serum TSH, thyroid hormones
      and thyroid autoantibodies. US of the thyroid was performed. RESULTS:
      Participants with decreased echogenicity (n=379) had a higher mean TSH (1.65
      mU/l) compared with subjects with normal echogenicity (1.21 mU/l, P<0.0001). The
      association was stronger in subjects with markedly decreased echogenicity (4.20
      mU/l, P<0.0001). A similar association was seen when the subjects were divided
      into subgroups according to the level of TSH; more subjects with high levels of
      TSH had decreased echogenicity (P<0.0001). Likewise, more subjects with high
      levels of TSH had an irregular echo pattern (P<0.0001). Subjects with decreased
      echogenicity had a higher risk of having thyroid autoantibodies than subjects
      without decreased echogenicity (P<0.0001). This association was stronger when
      echogenicity was markedly decreased. CONCLUSIONS: We demonstrated an association
      between hypoechogenicity at thyroid US and higher levels of serum TSH even in
      subjects without overt thyroid disease, suggesting decreased echogenicity as an
      early sign of thyroid dysfunction. Irregular echo pattern, whether accompanied by
      hypoechogenicity or not, was another possible marker of thyroid failure. This
      indicates a possible use of thyroid US in detecting early and subclinical thyroid
      dysfunction.

PMID- 16990654
TI  - Discrepant results in the diagnosis of GH deficiency with the insulin-tolerance
      test and the GHRH plus arginine test in patients with traumatic brain injury.
AB  - OBJECTIVE: Patients with traumatic brain injury (TBI) are at moderate risk of GH
      deficiency (GHD), requiring a diagnostic test with high specificity. The GHRH +
      arginine (GHRH + ARG) test has been recommended as a reliable alternative to the
      insulin-tolerance test (ITT) as a standard test with a cutoff level of 9 ng/ml.
      However, it has recently been questioned for its low specificity in obese
      subjects, and now BMI-dependent cut-off levels are available. In this study, we
      compared the ITT and GHRH + ARG test in patients with TBI. DESIGN: A cross
      sectional study METHODS: We performed an ITT and a GHRH + ARG test in 21 patients
      with TBI (6 women, 15 men; mean age 40.2 +/- 12.1 years; BMI 30.7 +/- 6.2). The
      number of patients classified discordantly as GH deficient by the ITT and the
      GHRH + ARG test with both classical and BMI-dependent cut-off levels was
      assessed. RESULTS: Using the GHRH + ARG test with the classical cut-off (<or= 9
      ng/ml), we identified 12 patients as GH deficient who had a normal GH response to
      ITT (> 3 ng/ml), and one patient as GH sufficient who had a blunted GH response
      to ITT (discordance rate 61.9%). All patients discordantly classified as GH
      deficient by the GHRH + ARG test had a BMI of >or= 28. With the BMI-dependent cut
      offs (4.2, 8.0, and 11.5 ng/ml in obese, overweight, and lean subjects
      respectively), only 3 of the 21 patients were discordantly classified
      (discordance rate 14.3%). CONCLUSIONS: Our results discourage the use of a cut
      off level of 9 ng/ml for the GHRH + ARG test in obese subjects. The diagnostic
      reliability of this test is improved with the BMI-dependent cut-offs.

PMID- 16990655
TI  - Endocrine dysfunction in patients operated on for non-pituitary intracranial
      tumors.
AB  - OBJECTIVE: Hypopituitarism frequently follows pituitary neurosurgery (NS) and/or
      irradiation. However, the frequency of hypothalamic-pituitary dysfunction after
      NS of non-pituitary intracranial tumors is unclear. The aim of this study was to
      assess the presence of endocrine alterations in patients operated on for
      intracranial tumors. DESIGN: This is a retrospective study. METHODS: We studied
      68 consecutive adult patients (28 female, 40 male, age 45.0 +/- 1.8 years; body
      mass index (BMI): 26.5 +/- 0.6) with intracranial tumors who underwent NS only (n
      = 17) or in combination with radiotherapy (RT) and/or chemotherapy (CT) (n = 51).
      In all subjects, basal endocrine parameters and the GH response to GHRH +
      arginine test (using BMI-dependent cut offs) were evaluated. RESULTS: In 20.6% of
      the patients, peripheral endocrinopathy related to CT and/or RT was present.
      Hypopituitarism was found in 38.2% of the patients. Total pituitary hormone,
      multiple pituitary hormone, and isolated pituitary hormone deficits were present
      in 16.2, 5.8, and 16.2% respectively. The most common pituitary deficits were, in
      decreasing order: LH/FSH 29.4%, GH 27.9%, ACTH 19.1%, TSH 17.7%, and diabetes
      insipidus 4.4%. Hyperprolactinemia was present in 13.2%. The prevalence of
      hypopituitarism was higher in patients who underwent NS only and with tumors
      located closely to the sella turcica, but a substantial proportion of patients
      with tumors not directly neighboring the sella also showed hypopituitarism.
      CONCLUSIONS: Hypopituitarism frequently occurs after NS for intracranial tumors.
      Also, exposure of these patients to CT and/or RT is frequently associated with
      peripheral endocrinopathies. Thus, endocrine evaluation and follow-up of patients
      treated for intracranial tumors should be performed on a regular basis.

PMID- 16990656
TI  - Changes in interleukin-6 and IGF system and their relationships in placenta and
      cord blood in newborns with fetal growth restriction compared with controls.
AB  - OBJECTIVES: The IGF system is central to fetal growth. Recently, the
      relationships between cytokines and the IGF system have been shown in specific
      tissues. It is unknown whether these occur in the placenta. The aim of this study
      was to assess whether interleukin-6 (IL-6) modulated the IGF system. METHODS:
      Whole villous tissue and cord serum were collected from fetal growth restriction
      (FGR) neonates diagnosed before birth with altered Doppler velocimetry and
      controls. Sixteen FGR and 20 controls, born after week 32 of gestation from
      elective Caesarean sections, were compared. Total RNA was extracted from the
      placenta samples, reverse transcribed, and real-time quantitative reverse
      transcriptase (RT)-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGF
      binding protein (IGFBP)-1, IGFBP-2, and IL-6. The same proteins were assayed in
      placenta lysates and cord serum using specific commercial kits and western
      immunoblotting. RESULTS: FGR subjects had significantly more IGFBPs-1 and -2, and
      IL-6 mRNA and corresponding proteins in the placenta. In particular, the less
      phosphorylated isoforms of IGFBP-1 were highly increased. IL-6 and IGFBPs-2 mRNA,
      and IL-6 and IGFBP-1 peptides were positively and significantly correlated in the
      placenta. The IGF-II peptide was also significantly increased in FGR placentas.
      In cord serum, IGFBPs-1 and -2 were significantly more elevated in the FGR
      neonates. Serum IL-6 was significantly and positively correlated with both IGFBP
      1 and IGFBP-2. CONCLUSIONS: The placenta of FGR neonates has higher IGF-II, IGFBP
      1, IGFBP-2, and IL-6 contents compared with controls. At birth, IGFBPs-1 and -2
      are increased in the cord blood of FGR neonates. IL-6 and IGFBP-2 gene
      expressions are closely related in the placenta. We suggest that the increase in
      IL-6 and IGFBP-2 could be subsequent to hypoxia and nutrient deficiency. As IGFBP
      2 has a strong affinity for IGF-II, which is crucial for fetal growth, it could
      be an important bioregulator of IGF-II in the placenta.

PMID- 16990657
TI  - Effects of short-term caloric restriction on circulating free IGF-I, acid-labile
      subunit, IGF-binding proteins (IGFBPs)-1-4, and IGFBPs-1-3 protease activity in
      obese subjects.
AB  - OBJECTIVE: Decreased levels of GH and total IGF-I have been reported in obesity.
      It has been hypothesized that increased free (biologically active) IGF-I levels
      generated from IGF-binding protein (IGFBP) protease activity could be the
      mechanism for the low GH release in dieting obese subjects. However, no published
      data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease
      activity in relation to GH release during a hypocaloric diet. The main purpose of
      this study was to determine free IGF-I, ALS, IGFBPs-1-4, and IGFBPs-1-3 protease
      activity in relation to 24-h GH release before and after a short-term very low
      calorie diet (VLCD). DESIGN: Six obese subjects before weight loss, five after an
      average weight loss of 36.1 kg, and five age-and sex-matched lean controls
      underwent a 4-day VLCD. All subjects were studied on two occasions, once during
      normal basic diet and again during the last day of the VLCD (1.6 MJ). METHODS:
      Free IGF-I was determined by a non-competitive immunoradiometric assay. RESULTS:
      Free IGF-I levels decreased in concert with increased ALS and unchanged blunted
      GH release after a VLCD in the obese subjects. IGFBPs-1-3 proteolytic activity
      was found to be unchanged by hypocaloric diet in all groups. CONCLUSIONS: We
      conclude that free IGF-I decreases after a short-term hypocaloric diet in obese
      subjects with no concomitant change in 24-h GH release. Circulating free IGF-I
      per se cannot be the main mechanism of the attenuated GH release in dieting obese
      subjects.

PMID- 16990658
TI  - Body composition is distinctly altered in Turner syndrome: relations to glucose
      metabolism, circulating adipokines, and endothelial adhesion molecules.
AB  - BACKGROUND: Body composition in Turner syndrome (TS) is altered with final height
      of TS decreased; anthropometry and bone mass distinctly changed. AIM: To describe
      total and regional distribution of fat and muscle mass in TS and the relation to
      measures of glucose metabolism, sex hormones, IGFs, and markers of inflammation
      and vascular function. MATERIAL AND METHODS: Fifty-four women with TS (mean age,
      42.5 +/- 9.7 years) and an age-matched group of controls (n = 55) were examined
      by dual-energy X-ray absorptiometry scans with determination of regional body
      composition and estimation of visceral fat and skeletal muscle mass. We
      determined maximal oxygen uptake and assessed physical activity using a
      questionnaire. We measured serum adiponectin, ghrelin, IGF-I, IGF-binding protein
      3 (IGFBP-3), estradiol, testosterone, sex hormone-binding globulin (SHBG),
      insulin, glucose, cytokines, vascular cell adhesion molecule-I, and intercellular
      cell adhesion molecule-I. Insulin sensitivity was estimated. Multiple linear
      regression models were used to examine the relationships between variables.
      RESULTS: TS had lower total lean body mass (LBM), while body mass index (BMI) and
      total fat mass (FM) were increased. We found increased visceral FM, and decreased
      trunk LBM, appendicular LBM, and skeletal muscle mass. VO2max and physical
      activity were significantly lower in TS, as were most hormone levels, except
      increased leptin. In multiple linear regression models, status (i.e. TS or
      control) was a consistent contributing variable. CONCLUSION: Profound changes are
      present in body composition in TS, with increased FM, and decreased skeletal
      muscle mass. Circulating hormones, VO2max, and insulin sensitivity influence body
      composition. The accumulation of visceral fat would predict a higher risk of
      development of the insulin resistance syndrome.

PMID- 16990659
TI  - Effect of DHEA-sulfate on adiponectin gene expression in adipose tissue from
      different fat depots in morbidly obese humans.
AB  - OBJECTIVE: A growing body of studies has demonstrated the inverse relationship
      between DHEA-sulfate (DHEA-S) and the pathological alterations associated with
      the metabolic syndrome. However, the mechanism by which DHEA-S treatment operates
      has not been elucidated completely. Adiponectin, an adipose-specific protein, is
      thought to have anti-diabetic and anti-atherosclerotic properties. Because fat
      depots differ in the impact of their relationship with the undesirable
      consequences of obesity, the aim of the present study was to investigate the
      effect of DHEA-S on adiponectin expression in both s.c. and visceral tissues in a
      morbidly obese population. DESIGN AND METHODS: We studied the in vitro expression
      of the adiponectin gene from paired biopsies of human visceral and s.c. adipose
      tissue, obtained from men and women (body mass index = 48.68+/- 7.43 kg/m2).
      Adipocytes were incubated for 24 h with or without DHEA-S. Adiponectin mRNA was
      measured by reverse transcription-quantitative PCR. RESULTS: In this population,
      DHEA-S plasma values were 141 +/- 105 microg/100 ml. Serum adiponectin values
      were under normal ranges. In basal conditions, s.c. tissue expressed higher
      amounts (58%) of adiponectin mRNA than visceral tissue (P = 0.027). Adiponectin
      expression was differentially regulated in the two depots by DHEA-S. There was a
      significant increase in adiponectin expression specifically in the visceral
      tissue (P = 0.020), but no significant effect of DHEA-S on the s.c. tissue (P =
      0.738). CONCLUSIONS: In the present study, for the first time in humans, we have
      shown that DHEA-S treatment is a strong upregulator of adiponectin gene
      expression in omental adipocytes, suggesting that the positive effects observed
      by DHEA-S treatment in humans suffering from metabolic syndrome could be exerted
      through overexpression of adiponectin in the visceral depot.

PMID- 16990660
TI  - Birth weight and risk of type 2 diabetes, abdominal obesity and hypertension
      among Chinese adults.
AB  - OBJECTIVE: To investigate the association between birth weight and risk of type 2
      diabetes, abdominal obesity and hypertension among Chinese adults. RESEARCH
      METHODS AND PROCEDURES: Nine hundred and seventy-three individuals from a
      population-based cross-sectional survey for the prevalence of type 2 diabetes
      conducted in Shanghai in 2002 were enrolled and followed up to 2004 with yearly
      examination. Birth weight was classified into four categories: <2500, 2500-2999,
      3000-3499 and >or=3500 g. RESULTS: In this study, there were 373 males and 600
      females, with a mean age of 46.2+/-9.9 years. Fasting plasma glucose was higher
      in subjects with the lowest birth weight (<2500 g) compared with those with the
      highest birth weight. Waist circumference and systolic blood pressure showed U
      shaped relationships with birth weight. Birth weight was found to be an
      independent risk factor for type 2 diabetes, abdominal obesity and hypertension.
      For type 2 diabetes, the crude odds ratio (95% confidence interval) was 3.17
      (1.48-6.78) in the lowest birth weight category when compared with that in the
      highest birth weight category (>or=3500 g) and the ratio increased to 3.97 (1.71
      9.22) after adjustment for related variables. The highest prevalence of type 2
      diabetes (34.5%) was observed among those with the lowest birth weight and
      abdominal obesity. CONCLUSIONS: Birth weight is inversely associated with the
      risk of type 2 diabetes. Subjects with the lowest or the highest birth weight
      were associated with a high risk of developing abdominal obesity and
      hypertension. Low birth weight coupled with abdominal obesity is a strong
      predictor of type 2 diabetes.

PMID- 16990661
TI  - Metabolic decompensation in children with type 1 diabetes mellitus associated
      with increased serum levels of the soluble leptin receptor.
AB  - OBJECTIVE: Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the
      soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim
      of our study was to investigate potential metabolic factors that may be
      associated with the induction of the sOB-R release from its membrane receptor.
      MATERIALS AND METHODS: Twenty-five children (aged between 1.5 and 17.0 years)
      were studied at the onset of T1DM. Blood samples were collected before (n = 25),
      during the first 18 h (mean +/- S.D. 11.1 +/- 4.3 h, n = 16) and 92 h (47.5 +/-
      22.5 h; n = 14) after beginning insulin therapy. Serum sOB-R and leptin levels
      were determined by in-house immunoassays. RESULTS: The sOBR-level and the molar
      sOB-R/leptin ratio were significantly higher before than after starting insulin
      treatment (P < 0.05). In contrast, leptin levels were significantly lower (P <
      0.05) before insulin therapy. The correlation between sOB-R and blood glucose (r
      = 0.49; P < 0.05), as well as sOB-R with parameters of ketoacidosis, such as pH
      (r = -0.72), base excess (r = -0.70), and bicarbonate (r = -0.69) (P < 0.0001) at
      diagnosis of T1DM remained significant during the first 18 h of insulin
      treatment. Multiple regression analysis revealed that base excess predicted 41.0%
      (P < 0.001), age 16.4% (P < 0.05), and height SDS 13.9% (P < 0.01) of the sOB-R
      variance. CONCLUSIONS: Metabolic decompensation in children with new onset T1DM
      is associated with dramatic changes of the leptin axis; serum levels of sOB-R are
      elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median
      11.3) in this condition may contribute to leptin insensitivity. Upregulation of
      the soluble leptin receptor appears to be a basic mechanism to compensate for
      intracellular substrate deficiency and energy-deprivation state.

PMID- 16990662
TI  - Decrement of postprandial insulin secretion determines the progressive nature of
      type-2 diabetes.
AB  - OBJECTIVE: Type-2 diabetes is a progressive disease. However, little is known
      about whether decreased fasting or postprandial pancreatic beta-cell
      responsiveness is more prominent with increased duration of diabetes. The aim of
      this study was to evaluate the relationship between insulin secretion both during
      fasting and 2 h postprandial, and the duration of diabetes in type-2 diabetic
      patients. DESIGN: Cross-sectional clinical investigation. METHODS: We conducted a
      meal tolerance test in 1466 type-2 diabetic patients and calculated fasting (M0)
      and postprandial (M1) beta-cell responsiveness. RESULTS: The fasting C-peptide,
      postprandial C-peptide, M0, and M1 values were lower, but HbA1c values were
      higher, in patients with diabetes duration > 10 years than those in other groups.
      There was no difference in the HbA1c levels according to the tertiles of their
      fasting C-peptide level. However, in a group of patients with highest
      postprandial C-peptide tertile, the HbA1c values were significantly lower than
      those in other groups. After adjustment of age, sex, and body mass index (BMI),
      the duration of diabetes was found to be negatively correlated with fasting C
      peptide (gamma = -0.102), postprandial C-peptide (gamma = -0.356), M0 (gamma = 
      0.263), and M1 (gamma = -0.315; P < 0.01 respectively). After adjustment of age,
      sex, and BMI, HbA1c was found to be negatively correlated with postprandial C
      peptide (gamma = -0.264), M(0) (gamma = -0.379), and M1 (gamma = -0.522),
      however, positively correlated with fasting C-peptide (gamma = 0.105; P < 0.01
      respectively). In stepwise multiple regression analysis, M0, M1, and homeostasis
      model assessment for insulin resistance (HOMA-IR) emerged as predictors of HbAlc
      after adjustment for age, sex, and BMI (R2 = 0.272, 0.080, and 0.056
      respectively). CONCLUSIONS: With increasing duration of diabetes, the decrease of
      postprandial insulin secretion is becoming more prominent, and postprandial beta
      cell responsiveness may be a more important determinant for glycemic control than
      fasting beta-cell responsiveness.

PMID- 16990663
TI  - Identification of factors differentially associated with isolated impaired
      fasting glucose and isolated post-load impaired glucose tolerance: the Hong Kong
      Cardiovascular Risk Factor Study.
AB  - BACKGROUND: The use of fasting and post-prandial glucose levels in the
      classification of hyperglycaemic states often identifies distinct subjects, but
      the factors determining these intermediate-isolated glucose intolerant states are
      yet to be clearly elucidated in Chinese subjects. METHODS: Representative
      subjects (n = 2769) were randomly recruited from the Hong Kong Chinese population
      and glycaemic status was determined using both fasting and 2h 75 g oral glucose
      tolerance test glucose levels. The relationship between the groups with isolated
      glucose intolerance and vascular risk factors was investigated using ANOVA and
      logistic regression analyses. RESULTS: Using either criterion, diabetes was
      identified in 265 (9.6%) subjects and glucose intolerance in 568 (20.5%)
      subjects. Of those 568, isolated impaired glucose tolerance (IGT) using the post
      load criterion was identified in 49.5% and isolated impaired fasting glucose
      (IFG) in 30.5%. Ageing and hyperinsulinaemia were common determinants of IGT and
      IFG; with small hip circumference a marker of poorer early life development and
      being born in China rather than Hong Kong, a possible low birth weight marker was
      also associated with IFG. Hypertension, hypertriglyceridaemia and poor education
      were also associated with IGT. When we looked for factors differentially
      associated with these glucose intolerant states, female sex, greater hip
      circumference, high triglyceride levels, low fasting insulin levels, and not
      being born in China were independently associated with isolated IGT compared with
      isolated IFG. CONCLUSION: Despite common antecedents to the glucose intolerant
      states, isolated IFG appeared to be particularly associated with early life
      development, and isolated IGT was more strongly associated with obesity-related
      determinants such as hypertriglyceridaemia.

PMID- 16990664
TI  - Early epitope- and isotype-specific humoral immune responses to GAD65 in young
      children with genetic susceptibility to type 1 diabetes.
AB  - OBJECTIVE: The pattern of the humoral immunity to disease-associated autoantigens
      may reflect the severity of the autoimmune disease process. The purpose of this
      study was to delineate the maturation of the humoral immunity to one of the main
      autoantigens in type 1 diabetes (T1D), glutamic acid decarboxylase (GAD65).
      DESIGN AND METHODS: Serum samples were obtained for the detection of epitope- and
      isotype-specific antibodies sequentially with short intervals from 36 young
      children with HLA-conferred genetic susceptibility to T1D starting from the first
      appearance of GAD65Ab. During prospective observation, ten children developed
      T1D. Antibodies were analyzed using biotinylated anti-human immunoglobulin (Ig)
      antibodies and chimeric GAD molecules in radio-binding assays. RESULTS: The
      immune response to GAD65 started as reactivity to the middle region and spread
      rapidly to the C-terminal region. IgG1 antibodies dominated among the isotypes
      from the first appearance of GAD65Ab, while other IgG subclasses were observed to
      a lesser extent. IgG4 antibodies emerged clearly as the last IgG subclass. A
      broad initial response comprising three to four IgG subclasses and the lack of an
      emerging IgG4 response during follow-up was associated with increased risk for
      progression to clinical diabetes (P<0.05). CONCLUSIONS: The humoral response to
      GAD65 epitope clusters is relatively uniform in young children, whereas there is
      conspicuous individual variation in IgG subclass responses except for IgG1. A
      narrow initial IgG subclass response to GAD65 and the emergence of IgG4
      antibodies were characteristic of those who remained non-diabetic over the first
      few years of GAD65 autoimmunity.

PMID- 16990665
TI  - Will the combination of US contrast microbubbles and high-intensity focused
      ultrasound enable noninvasive brain surgery?

PMID- 16990666
TI  - An opportunity for radiology: recommendations from the educational summit.

PMID- 16990667
TI  - The state of radiology in 2006: very high spatial resolution but no visibility.

PMID- 16990668
TI  - Procedural simulation: a primer.

PMID- 16990669
TI  - Quantitative MR imaging in Alzheimer disease.
AB  - Alzheimer disease (AD) is the most common type of dementia. It currently affects
      approximately 4 million people in the United States. AD is a progressive
      neurodegenerative disorder characterized by the gradual deposition of neuritic
      plaques and neurofibrillary tangles in the brain, which is thought to occur
      decades before the onset of clinical symptoms. Identification of people at risk
      before the clinical appearance of dementia has become a priority due to the
      potential benefits of therapeutic intervention. Although atrophy of medial
      temporal lobe structures has been shown to correlate with progression of AD, a
      growing number of recent reports have indicated that such atrophy may not be
      specific to AD. To improve diagnostic specificity, new quantitative magnetic
      resonance (MR) imaging methods are being developed that exploit known pathogenic
      mechanisms exclusive to AD. This article reviews the MR techniques that are
      currently available for the diagnostic assessment of AD.

PMID- 16990670
TI  - Single reading with computer-aided detection and double reading of screening
      mammograms in the United Kingdom National Breast Screening Program.
AB  - PURPOSE: To retrospectively determine if the use of a computer-aided detection
      (CAD) system can improve the performance of single reading of screening
      mammograms to match that of double reading in the United Kingdom. MATERIALS AND
      METHODS: Local research ethics committee approval was obtained; informed consent
      was not required. This study included a sample of 10 267 mammograms obtained in
      women aged 50 years or older who underwent routine screening at one of two breast
      screening centers in 1996. Mammograms that were double read in 1996 were randomly
      allocated to be re-read by eight different radiologists using CAD. The cancer
      detection and recall rates from double reading and single reading with CAD were
      compared. Statistical significance and confidence intervals were calculated with
      the McNemar test to account for the matched nature of the data. RESULTS: Single
      reading with CAD led to a cancer detection rate that was significantly (P = .02)
      higher than that achieved with double reading: 6.5% more cancers were detected by
      means of single reading with CAD than by means of double reading. However, the
      recall rate was higher for single reading with CAD than for double reading (8.6%
      vs 6.5%, respectively; P < .001). This was equivalent to relative increases of
      15% and 32% in the cancer detection and recall rates, respectively. CONCLUSION:
      Single reading with CAD leads to an improved cancer detection rate and an
      increased recall rate.

PMID- 16990671
TI  - Performance benchmarks for screening mammography.
AB  - PURPOSE: To retrospectively evaluate the range of performance outcomes of the
      radiologist in an audit of screening mammography by using a representative sample
      of U.S. radiologists to allow development of performance benchmarks for screening
      mammography. MATERIALS AND METHODS: Institutional review board approval was
      obtained, and study was HIPAA compliant. Informed consent was or was not obtained
      according to institutional review board guidelines. Data from 188 mammographic
      facilities and 807 radiologists obtained between 1996 and 2002 were analyzed from
      six registries from the Breast Cancer Surveillance Consortium (BCSC). Contributed
      data included demographic information, clinical findings, mammographic
      interpretation, and biopsy results. Measurements calculated were positive
      predictive values (PPVs) from screening mammography (PPV(1)), biopsy
      recommendation (PPV(2)), biopsy performed (PPV(3)), recall rate, cancer detection
      rate, mean cancer size, and cancer stage. Radiologist performance data are
      presented as 50th (median), 10th, 25th, 75th, and 90th percentiles and as graphic
      presentations by using smoothed curves. RESULTS: There were 2 580 151 screening
      mammographic studies from 1 117 390 women (age range, <30 to >/=80 years). The
      respective means and ranges of performance outcomes for the middle 50% of
      radiologists were as follows: recall rate, 9.8% and 6.4%-13.3%; PPV(1), 4.8% and
      3.4%-6.2%; and PPV(2), 24.6% and 18.8%-32.0%. Mean cancer detection rate was 4.7
      per 1000, and the median [corrected] mean size of invasive cancers was 13 mm. The
      range of performance outcomes for the middle 80% of radiologists also was
      presented. CONCLUSION: Community screening mammographic performance measurements
      of cancer outcomes for the majority of radiologists in the BCSC surpass
      performance recommendations. Recall rate for almost half of radiologists,
      however, is higher than the recommended rate.

PMID- 16990672
TI  - Improving the concordance of mammography assessment and management
      recommendations.
AB  - PURPOSE: To retrospectively compare the concordance of initial and final
      assessment categories for mammograms with management recommendations made before
      and after the final rules of the Mammography Quality Standards Act (MQSA) were in
      effect for screening and diagnostic mammography. MATERIALS AND METHODS: The study
      included mammograms from 1996 to 2001 from the seven mammography registries of
      the Breast Cancer Surveillance Consortium (BCSC). The authors defined the pre
      MQSA period as January 1, 1996-April 27, 1999, and the post-MQSA period as April
      28, 1999-December 31, 2001 (2470151 screening and 194199 diagnostic mammograms).
      Assessment was cross-classified according to management recommendation. Changes
      in concordance between assessment and recommendation were evaluated by year and
      by period (before and after MQSA) for computer-linked data and for all data by
      using Pearson chi(2) test to evaluate differences. Mantel-Haenszel chi(2) test
      was used to measure change in concordance over time. Each registry and the BCSC
      Statistical Coordinating Center had a Federal Certificate of Confidentiality and
      approval from each institution's review board for protection of human subjects to
      collect and send data to coordinating center and conduct research with these
      data. Active consent was required at only one site in this HIPAA-compliant study.
      RESULTS: Concordance increased significantly in the post-MQSA period for Breast
      Imaging Reporting and Data System categories 3-5 assessments at both screening
      and diagnostic mammography. The most substantial improvements were in the use of
      the management recommendation for "additional imaging," which decreased from 41%
      in 1996 to 15% in 2001 for screening mammograms with an initial assessment of
      category 4 (P < .001). Recommendation for short-interval follow-up in women with
      screening mammograms with a category 3 final assessment increased from 51% in
      1996 to 76% in 2001 (P < .001). Concordance for diagnostic mammograms assigned
      category 0 improved from 65% in the pre-MQSA period to 81% in the post-MQSA
      period (P < .001). CONCLUSION: This analysis demonstrates that over a relatively
      short period of time, major improvement in radiology reporting has occurred.

PMID- 16990673
TI  - Microbubble contrast agent with focused ultrasound to create brain lesions at low
      power levels: MR imaging and histologic study in rabbits.
AB  - PURPOSE: To evaluate magnetic resonance (MR) imaging-based thermometry for
      predicting the onset and spatial extent of lesions produced by focused ultrasound
      combined with a microbubble contrast agent (Optison; GE Healthcare, Milwaukee,
      Wis) and to compare the resulting induced temperature increase and threshold for
      damage with those in studies performed without the agent. MATERIALS AND METHODS:
      The experiments were approved by the animal care committee. Fifty-three locations
      in the brains of 15 rabbits were sonicated with various exposure parameters by
      using a 1.5-MHz focused ultrasound transducer. MR imaging was used to map the
      temperature rise and, along with light microscopy, to examine the lesions.
      Diameters of isotherms created from thermometry were compared with the resulting
      lesions by using Bland-Altman analysis and linear regression. The minimum
      acoustic power necessary for lesion creation was determined, and the apparent
      temperature threshold for damage was calculated with probit analysis. These
      thresholds were compared with prior work performed without the contrast agent.
      The heating induced with the microbubbles was compared with that in sonications
      performed without them by using a t test. RESULTS: The MR imaging-mapped
      temperature distributions matched the shape of the lesions. The diameters of
      isotherms correlated well with diameters measured at contrast material-enhanced
      MR imaging (mean difference between measurements, 0.0 mm +/- 0.5; R = 0.93). The
      temperature increase with microbubbles was statistically larger (P < .01) than
      for sonications performed without microbubbles. In some locations (mostly
      continuous wave exposures), damage was observed along the ultrasound beam path.
      The time-averaged acoustic power damage threshold was reduced by 91% for 10
      second exposures when compared with earlier studies performed without
      microbubbles. The probability of producing lesions was 50% at a temperature
      increase of 5.9 degrees C, 5.5 degrees C lower than was observed earlier without
      the agent. CONCLUSION: MR imaging-based temperature measurements appeared to
      correlate with focused ultrasound-induced lesions in the brain when microbubbles
      were present, even though the temperature appeared to be below the threshold for
      thermal damage.

PMID- 16990674
TI  - Characterization of intimal changes in coronary artery specimens with MR
      microscopy.
AB  - PURPOSE: To determine if magnetic resonance (MR) microscopy can yield images
      sufficient for discriminating early progressive atherosclerotic lesions from
      nonprogressive atherosclerotic lesions in human coronary arteries. MATERIALS AND
      METHODS: Institutional review board approval and informed consent were not
      required. Seventeen coronary artery segments (mean diameter, 2.8 mm +/- 1.0
      [standard deviation]) were collected within 36 hours after death from 11 cadavers
      (six men, five women; age range at death, 33-65 years). Quantitative T1, T2,
      intensity-weighted (IW), and magnetization transfer (MT) maps were acquired with
      a 9.4-T vertical-bore magnet. Coronary artery lesions were classified as adaptive
      intimal thickening (AIT), pathologic intimal thickening (PIT), or intimal
      xanthoma (IXA). Internal anatomic fiducial landmarks and stains were applied to
      proximal and epicardial vessel surfaces and used to register histologic sections
      with MR images and thus enable comparison of MR images and Movat pentachrome
      stained histologic specimens. Unique 0.0012-0.0287-cm(2) regions of interest were
      visually identified on quantitative T1, T2, MT, and IW maps of AIT, IXA, and PIT
      lesions. Distributions of T1, T2, MT, and IW values were compared with Student t
      and Wilcoxon two-sample tests. RESULTS: MR microscopic images of nonprogressive
      AIT and IXA lesions revealed two intimal layers. The luminal intima had higher T1
      and T2 values and lower MT values than did the medial intima; these findings were
      consistent with compositional differences observed in histologic sections. In the
      IXA lesion, T2 values of both intimal layers were markedly reduced when compared
      with T2 values of AIT lesions because of the accumulation of lipid-laden
      macrophages in both layers. Progressive PIT lesions had a typical multilayered
      appearance or foci with a short T2 relaxation time and low IW values; these
      features were not observed in AIT or IXA lesions. CONCLUSION: MR microscopy
      enabled identification of morphologic arterial wall features that enable
      discrimination of progressive PIT lesions from nonprogressive AIT or IXA lesions.

PMID- 16990675
TI  - MR imaging of in vivo recruitment of iron oxide-labeled macrophages in
      experimentally induced soft-tissue infection in mice.
AB  - PURPOSE: To evaluate the feasibility of magnetic resonance (MR) imaging in
      depicting in vivo recruitment of iron oxide-labeled macrophages in experimentally
      induced soft-tissue infection. MATERIALS AND METHODS: The study was performed
      according to the guidelines of the U.S. National Institutes of Health and
      recommendations of the committee on animal research. The protocol was approved by
      the local institutional review committee on animal care. Experimental soft-tissue
      infection in 12 mice was induced by inoculation with a 5 x 10(7) colony-forming
      units of Staphylococcus aureus into the left calf. Peritoneal macrophages were
      harvested from thioglycollate-treated mice, cultured, and labeled with iron oxide
      in vitro. The iron oxide-labeled macrophage (macrophage group, n = 6) or iron
      oxide solution (control group, n = 6) was administered through the tail vein. The
      left calf of the mice was imaged on days 2 and 3 with a 4.7-T MR unit. Changes in
      relative signal intensity (SI) and pattern of contrast material enhancement
      (macrophage distribution) were analyzed and compared with histopathologic
      findings. Statistical analysis was performed with the Wilcoxon matched-pairs
      signed rank test. RESULTS: On MR images obtained 24 hours after administration of
      macrophage labeled with iron oxide, a band-shaped lower SI zone was noted in the
      abscess wall, which corresponded to the distribution of the iron oxide-labeled
      macrophages at histopathologic examination. The relative SI of the abscess wall
      significantly decreased after injection of iron oxide-labeled macrophages
      (median, 0.42) compared with that before injection (median, 1.23) (P = .031). In
      the control group, the SI change after administration of iron oxide solution was
      not significant (P = .688). CONCLUSION: Homing of intravenously administered iron
      oxide-labeled macrophages can be monitored with MR imaging and may provide a tool
      to investigate interactions between macrophages and the invading pathogens.

PMID- 16990676
TI  - Pancreas: optimal scan delay for contrast-enhanced multi-detector row CT.
AB  - PURPOSE: To prospectively determine optimal scan delays for multiphasic contrast
      medium-enhanced imaging of the pancreas with multi-detector row computed
      tomography (CT). MATERIALS AND METHODS: This study was approved by an
      institutional review committee, and patients gave written informed consent. One
      hundred ninety-one patients underwent three-phase CT of the pancreas after
      receiving intravenous contrast medium with a fixed duration injection of 30
      seconds. Patients were prospectively assigned among four groups with scan delays
      of 25, 45, and 65 seconds (group 1); 30, 50, and 70 seconds (group 2); 35, 55,
      and 75 seconds (group 3); and 40, 60, and 80 seconds (group 4). Mean CT numbers
      of abdominal aorta, spleen, pancreatic parenchyma, superior mesenteric artery and
      vein, splenic vein, and hepatic parenchyma were measured, and increases in
      contrast enhancement on enhanced images were assessed. Qualitative analysis was
      performed with a four-point scale. RESULTS: Abdominal aorta and superior
      mesenteric artery enhanced at a mean of 35 seconds from the start of injection
      (both P < .001). Pancreatic parenchyma enhanced most intensely at 35-45 seconds
      (P < .001) with a peak enhancement at the mean of 40 seconds. Liver parenchyma
      enhanced most intensely at 55-65 seconds with a peak at 60 seconds (P < .001).
      The mean time to peak enhancement was 45 seconds for the splenic vein and 55
      seconds for the superior mesenteric vein. Qualitative results were in good
      agreement with quantitative results (both P < .001). CONCLUSION: With the
      injection protocol used in this study, optimal scan delays for imaging the
      pancreas were 30-35 seconds for the abdominal aorta and the superior mesenteric
      artery, 35-45 seconds for the pancreas, 45 seconds for the splenic vein, and 55
      seconds or later for the liver.

PMID- 16990677
TI  - Mild cognitive impairment: apparent diffusion coefficient in regional gray matter
      and white matter structures.
AB  - PURPOSE: To prospectively evaluate regional alterations in the apparent diffusion
      coefficient (ADC) of cortical gray and white matter and subcortical structures
      that are known to be involved in mild cognitive impairment (MCI). MATERIALS AND
      METHODS: Magnetic resonance (MR) imaging was performed in 13 patients with MCI
      (nine men, four women; mean age, 74 years +/- 6 [standard deviation]) and 13
      healthy elderly control subjects (seven men, six women; mean age, 75 years +/-
      4). This study was approved by the institutional review board and was HIPAA
      compliant. Each subject gave informed consent. ADC was measured from manually
      drawn regions of interest (ROIs) of the hippocampus, parahippocampal gyrus,
      amygdala, corpus callosum, and anterior and posterior cingulate gyrus and from
      automatically defined frontal, parietal, occipital, and temporal lobes by using
      template masking. ROIs were outlined on anatomic images then mapped onto ADC maps
      by using coregistration transformation matrix. A skeleton-based region
      competition segmentation algorithm was used for segmentation of gray and white
      matter. The group difference in ADC values was assessed with independent-sample t
      tests. Pearson correlation analysis was used to examine the correlation of ADC
      values with age and memory test scores. RESULTS: Higher ADCs were found in
      hippocampus, temporal lobe gray matter, and corpus callosum of patients with MCI
      compared with that of control subjects (P < .05). By pooling all subjects
      together, an elevated hippocampal ADC was significantly correlated with worse
      memory performance scores in 5-minute and 30-minute delayed word-list recall
      tasks (P < .05). CONCLUSION: ADCs from gray and white matter of different brain
      regions can be analyzed by applying an automated template-masking method in
      conjunction with a skeleton-based region competition segmentation algorithm.

PMID- 16990678
TI  - Detection of simulated multiple sclerosis lesions on T2-weighted and FLAIR images
      of the brain: observer performance.
AB  - PURPOSE: To determine observer performance in the detection of multiple sclerosis
      (MS) lesions on magnetic resonance (MR) images of the brain and to assess the
      dependence of observer performance on lesion size, parenchymal location, pulse
      sequence, and supratentorial versus infratentorial level. MATERIALS AND METHODS:
      This HIPAA-compliant protocol was approved by the institutional review board, and
      previously acquired MR data from a healthy volunteer and a patient with MS were
      used to derive parameter maps, with waiver of informed consent. Parameter maps
      and image simulator software were used to generate 320 phantom brain images with
      simulated supratentorial and infratentorial MS lesions. Images were displayed
      with T2-weighting or fluid-attenuated inversion recovery (FLAIR) contrast. Four
      readers independently evaluated the images, rating lesions on a five-point
      certainty scale. Observer performance was measured by using the area under the
      alternative free-response receiver operating characteristic curve (A(1)), and
      significance was determined with the z test. RESULTS: Pooled A(1) scores were
      significantly better for FLAIR imaging (0.96 +/- 0.01 [standard error]) than for
      T2-weighted MR imaging (0.89 +/- 0.04) supratentorially (P = .05) but were
      similar for FLAIR imaging (0.90 +/- 0.06) and T2-weighted MR imaging (0.88 +/-
      0.05) infratentorially. A(1) scores for cortical, deep white matter, and
      periventricular lesions were 0.93 +/- 0.05, 0.97 +/- 0.02, and 0.89 +/- 0.04,
      respectively, for FLAIR imaging and 0.77 +/- 0.06, 0.99 +/- 0.01, and 0.89 +/-
      0.05, respectively, for T2-weighted MR imaging. FLAIR scores were significantly
      higher than T2-weighted scores for cortical lesions. Linear correlation was found
      between A(1) and lesion size (r = 0.5). CONCLUSION: Supratentorially, performance
      was better with FLAIR imaging than with T2-weighted MR imaging. Infratentorially,
      performance was moderate with both modalities. Observers did better with FLAIR
      imaging in the detection of cortical lesions, and performance improved with
      increasing lesion size.

PMID- 16990679
TI  - Prospective evaluation of vascular complications after liver transplantation:
      comparison of conventional and microbubble contrast-enhanced US.
AB  - PURPOSE: To prospectively compare diagnostic performance of conventional Doppler
      ultrasonography (US) and microbubble contrast material-enhanced US for assessment
      of vascular complications after liver transplantation, with clinical follow-up or
      angiography as reference standard. MATERIALS AND METHODS: This study was approved
      by institutional review board and was HIPAA compliant. Written informed consent
      was obtained. Seventy-two patients (49 men, 23 women; average age, 52.3 years)
      were included in this study. Patients who had undergone liver transplantation
      underwent conventional color Doppler and contrast-enhanced US of the liver.
      Quality of hepatic artery (HA) and portal vein (PV) visualization, contrast
      material arrival time, and time for complete evaluation of vasculature were
      compared for both techniques. McNemar test was used to compare vascular flow
      visualization scores; Student t test was used to compare mean study times with
      both techniques. Patients without HA flow at Doppler US underwent angiography;
      those with flow were followed up clinically. McNemar test was used to compare
      sensitivity of both techniques. RESULTS: Contrast-enhanced US helped
      significantly improve flow visualization in hepatic vessels (P < .001). Mean
      contrast material arrival time was 13.7 seconds +/- 3.8 (standard deviation) in
      proper HA and 20.7 seconds +/- 6.3 in PV. Mean study time decreased from 27.4
      minutes +/- 13.9 to 9.3 minutes +/- 4.5 (P < .01). Doppler US failed to depict HA
      flow in eight patients; contrast-enhanced US showed flow in six and no flow in
      two of these patients. Follow-up results confirmed contrast-enhanced US findings.
      Sensitivity, specificity, and accuracy for Doppler US were 91.3%, 100%, and
      91.5%, respectively. Sensitivity, specificity, and accuracy of contrast-enhanced
      US were all 100%. Sensitivity and accuracy values of the two techniques were
      significantly different (P < .014); there was no significant difference in
      specificity (P > .99) CONCLUSION: Contrast-enhanced US helped improve flow
      visualization in the HA and PV, decrease scanning time, and correctly
      differentiate between thrombosis and a patent artery in patients without HA flow
      at conventional Doppler US.

PMID- 16990680
TI  - Tesio catheter access for long-term maintenance hemodialysis.
AB  - PURPOSE: To retrospectively determine the long-term outcome (>6 months) of
      placement of tunneled hemodialysis catheters. MATERIALS AND METHODS: The HIPAA
      compliant study protocol was approved by the Committee on Human Research, which
      waived the requirement for informed consent. The records of patients who
      underwent hemodialysis with the Tesio system (Medcomp, Harleysville, Pa) at a
      single outpatient dialysis unit between March 1994 and March 2004 were reviewed.
      The length of catheter access and the requirements for percutaneous revision were
      recorded, and unassisted- and assisted-access survival times were computed by
      using the Kaplan-Meier method. RESULTS: Three hundred three primary Tesio
      accesses were created in 200 patients (mean age, 62.3 years +/- 16.3 [standard
      deviation]; 102 women [51.0%]). Fifty-nine of 303 accesses (19.5%) were
      percutaneously revised with catheter exchange. During follow-up, 200 of 303
      accesses (66.0%) were terminated (117 because they were no longer needed and 83
      because of catheter malfunction), and 103 (34.0%) accesses were functioning at
      the time of last follow-up. The mean duration of catheter access was 247 days
      (range, 3-2016 days). One hundred twenty-six (41.6%) accesses remained in use for
      more than 6 months; 50 (16.5%), for more than 1 year; 20 (6.6%), for more than 2
      years; 14 (4.6%), for more than 3 years; and five (1.7%), for more than 4 years.
      Assisted-access survival was 78.1%, 60.0%, 51.5%, 51.5%, and 46.8% at 6 months
      and 1, 2, 3, and 4 years, respectively. CONCLUSION: Tesio catheters frequently
      function for periods longer than 6 months and, when necessary, they can function
      for many years.

PMID- 16990683
TI  - Case 99: Canavan disease.

PMID- 16990684
TI  - The MCA Dot Sign.

PMID- 16990685
TI  - Gadopentetate dimeglumine and FDG uptake in liver metastases.

PMID- 16990686
TI  - MR imaging findings in the hands.

PMID- 16990687
TI  - MR imaging of upper motor neuron compromise in amyotrophic lateral sclerosis.

PMID- 16990688
TI  - Outcome of coronary revascularisation in diabetes.

PMID- 16990690
TI  - Pathophysiology and management of recurrent hypoglycaemia and hypoglycaemia
      unawareness in diabetes.
AB  - Iatrogenic hypoglycaemia is a well-known complication of insulin therapy in
      patients with diabetes mellitus and a limiting factor for glycaemic control. In a
      setting of endogenous insulin deficiency (type 1 and advanced type 2 diabetes),
      one episode of hypoglycaemia reduces both counterregulatory hormone responses to
      and subjective awareness of subsequent hypoglycaemia, thus impairing
      physiological defences against hypoglycaemia. This phenomenon may lead to a
      vicious cycle of recurrent hypoglycaemia and glucose counterregulatory failure,
      of which hypoglycaemia unawareness (i.e. the inability to perceive symptoms of
      hypoglycaemia) is the clinical representative. The underlying mechanism of
      hypoglycaemia-induced counterregulatory failure has not yet been disclosed.
      Patients with clinical hypoglycaemia unawareness are at high risk of severe
      hypoglycaemia that requires third-party assistance. Management options include
      avoidance of hypoglycaemic events and optimisation of insulin therapy to limit
      deterioration of glycaemic control associated with hypoglycaemia avoidance.
      Several counterregulatory-stimulating agents have been found to improve
      hypoglycaemic awareness in small clinical trials, but none have been tested in
      sufficiently large randomised studies to justify their use in daily practice.
      More research is required to elucidate the pathogenesis of counterregulatory
      failure and to develop adequate treatment strategies.

PMID- 16990691
TI  - Obstructive sleep apnoea syndrome and genes.
AB  - Obstructive sleep apnoea (OSA) is a complex disease entity strongly influenced by
      genetic factors, especially those that affect obesity and fat distribution, upper
      airway muscle tone, craniofacial morphology, ventilatory control and sleep,
      giving rise to the OSA phenotype. OSA can also be considered a metabolic syndrome
      which adversely affects multiple organ systems, especially the cardiovascular
      system and the brain. The most widely used clinical marker for the diagnosis of
      OSA is the apnoea-hypopnoea index, calculated by polysomnography. A percentage of
      35 to 40% of its variance can be attributed to genetic factors. Therefore, the
      identification and elucidation of the genes implicated in the pathogenesis of OSA
      becomes a matter of extensive research and could lead to the development of
      therapeutic agents that can have a beneficial effect on the natural course of
      OSA.

PMID- 16990692
TI  - Preoperative pharmacological management of phaeochromocytoma.
AB  - Phaeochromocytoma is a rare catecholamine-secreting neuroendocrine tumour with a
      high cardiovascular morbidity and mortality if left untreated. Surgical resection
      is the only curative therapy. During surgery there is a high risk of massive
      release of catecholamines, which can result in potentially fatal hypertensive
      crises and cardiac arrhythmias. Administration of vasoactive drugs such as
      (non)selective alpha- and beta-antagonists and calcium channel blocking agents
      have reduced the operation risk. Guidelines for the preoperative medical
      management of the patient with a phaeochromocytoma are mainly based on
      retrospective studies and case reports. We reviewed the relevant literature on
      this subject. In addition, we compared the several preoperative treatment
      protocols of the eight university medical centres in the Netherlands.

PMID- 16990693
TI  - Long-term clinical outcome of patients with diabetes proposed for coronary
      revascularisation.
AB  - BACKGROUND: The optimal method of revascularisation in diabetic patients with
      coronary artery disease (CAD) remains controversial. It was our aim to evaluate
      long-term outcome in diabetic patients with CAD in daily practice, in whom an
      invasive approach was considered. METHODS: A prospective follow-up study of
      patients with CAD in whom a coronary revascularisation procedure was considered.
      Follow-up data were obtained on the vital status up to ten years after inclusion.
      RESULTS: Of the 872 included patients, a total of 107 patients (12%) had
      diabetes. Patients with diabetes were older and more frequently female. Long-term
      mortality was higher in diabetics than nondiabetics (36 vs 25%, p = 0.01). This
      association was observed in both medically treated patients (65 vs 31%, p = 0.01)
      and in those treated by percutaneous coronary intervention (41 vs 24%, p = 0.02).
      There was, however, no difference in mortality in diabetes vs nondiabetes
      patients after coronary artery bypass grafting (24 vs 24%, p = 0.89).
      Multivariate analysis did not change these findings. CONCLUSION: Diabetic
      patients with significant CAD had a higher long-term mortality compared with
      patients without diabetes. In patients with diabetes, survival was highest after
      coronary artery bypass grafting and appeared to be comparable between diabetic
      and nondiabetic patients. Complete revascularisation may decrease the influence
      of diabetes on survival.

PMID- 16990694
TI  - Fever and high lactate dehydrogenase in HIV-positive patients from the Antilles
      and Surinam: histoplasmosis?
AB  - We describe four cases of HIV-positive patients, two from Surinam, one from the
      Dutch Antilles and one from Nigeria, who presented with a febrile illness and a
      high lactate dehydrogenase plasma level. In all four, the diagnosis of
      disseminated histoplasmosis was made, in three of them by liver biopsy. Two
      patients had retinal abnormalities compatible with a systemic fungal infection.
      Three patients were treated successfully with antifungal agents. One patient
      died. Between 2000 and 2006, only 14 patients with HIV have been found to have
      histoplasmosis in the Netherlands. Although histoplasmosis is not endemic in the
      Netherlands, physicians are more likely to see cases because of a growing number
      of HIV -positive immigrants from endemic regions.

PMID- 16990695
TI  - Sporadic porphyria cutanea tarda due to haemochromatosis.
AB  - Haemochromatosis is a hereditary iron-overload syndrome caused by increased
      intestinal iron absorption and characterised by accumulation of potentially toxic
      iron in the tissues. Sometimes this disease presents as a cutanea porphyria. We
      describe a patient with joint complaints and blistering skin lesions on sun
      exposed skin. After identifying the porphyria cutanea tarda by urine analysis we
      found that the serum activity of uroporphyrinogen decarboxylase (UROD) was
      normal, meaning a partial inactivation of UROD in liver tissue due to external
      factors. Further investigation showed the homozygous Cys282Tyr missense mutation
      and high levels of serum ferritin. It is important to recognise the symptoms of
      iron overloading at an early stage because hereditary haemochromatosis needs to
      be treated immediately. We therefore advocate routine sampling of ferritin levels
      in patients with unexplained joint complaints.

PMID- 16990696
TI  - Diabetes insipidus and adrenal insufficiency in a patient with metastatic breast
      cancer.
AB  - A patient previously treated for bilateral breast cancer with mastectomy,
      radiation therapy and in remission on hormonal therapy for more than five years
      presented with abdominal symptoms from breast cancer relapse. She developed
      inappropriate polyuria and hypernatraemia, which responded to desmopressin. In
      combination with the absence of a high signal from the posterior lobe of the
      pituitary on MRI , these data indicated the presence of partial central diabetes
      insipidus. The anterior pituitary showed partial failure (low follicle
      stimulating hormone, luteinising hormone and insulin-like growth factor-1
      levels). Furthermore, primary adrenal insufficiency had developed, ascribed to
      bilateral tumour invasion of the adrenals. This rare combination of
      endocrinological failures in a patient with metastatic breast cancer is
      discussed.

PMID- 16990697
TI  - A patient with diabetes mellitus and recurrent peristomal bleeding.

PMID- 16990698
TI  - Gastro-oesophageal reflux in morbidly obese patients is associated with hiatal
      hernias but not with body mass index.

PMID- 16990699
TI  - Topics on the Na+/Ca2+ exchanger: pharmacological characterization of Na+/Ca2+
      exchanger inhibitors.
AB  - Using the whole-cell voltage clamp, we examined acute effects of various agents
      on Na(+)/Ca(2+) exchange current (I(NCX)) in guinea-pig cardiac ventricular cells
      and transfected cells. Among the antiarrhythmic drugs, amiodarone, bepridil,
      dronedarone, cibenzoline, azimilide, and aprindine inhibited I(NCX) in a
      concentration-dependent manner. We also investigated the effects on NCX of 2,3
      buanedione monoxim (BDM) and selective NCX inhibitors such as KB-R7943, SEA0400,
      and SN-6. The presence of trypsin in the pipette solution attenuated the
      inhibitory effects on NCX of amiodarone, bepridil, and BDM, suggesting that these
      drugs inhibit NCX from the cytosolic side. In contrast, the trypsin-insensitive
      NCX inhibitors were aprindine, azimilide, dronedarone, cibenzoline, KB-R7943,
      SEA0400, and SN-6. KB-R7943, SEA0400, and SN-6 suppressed the uni-directional
      outward I(NCX) more potently than the uni-directional inward I(NCX). The
      mechanism of this mode-dependency is unknown, but is suggested to be related to
      intracellular Na(+) concentration.

PMID- 16990700
TI  - Topics on the Na+/Ca2+ exchanger: involvement of Na+/Ca2+ exchanger in the
      vasodilator-induced vasorelaxation.
AB  - Many kinds of vasodilators induce relaxation of the vascular smooth muscle cells
      (VSMCs) through the production of cyclic AMP (cAMP) or cyclic GMP (cGMP). The
      relaxant effects mediated by these second messengers are thought to be mainly due
      to the decrease in intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as
      the decrease in Ca(2+) sensitivity of the contractile apparatus of VSMCs. To
      explain the cAMP- or cGMP-mediated decrease in [Ca(2+)](i), several mechanisms
      have been proposed, including the inhibition of Ca(2+) influx due to a
      hyperpolarization, a stimulation of Ca(2+) uptake into the intracellular store,
      and an increase in Ca(2+) extrusion from VSMCs by stimulation of sarcolemmal
      Ca(2+)-pump. VSMCs have two major systems for Ca(2+) extrusion, namely,
      sarcolemmal Ca(2+)-pump and Na(+)/Ca(2+) exchanger (NCX). However, the
      involvement of NCX in the vasodilator-induced relaxation of VSMCs has not been
      well established. In this article, the possible involvement of NCX in the
      vasodilator-induced relaxation of VSMCs will be reviewed.

PMID- 16990701
TI  - Inhibition of arachidonic acid release by cytosolic phospholipase A2 is involved
      in the antiapoptotic effect of FK506 and cyclosporin a on astrocytes exposed to
      simulated ischemia in vitro.
AB  - In the present study, we investigated whether the protective effect of FK506 and
      cyclosporin A (CsA) against in vitro ischemic injury of astrocytes might be
      mediated through attenuation of cytosolic isoform of phospholipase A(2) (cPLA(2))
      expression and activity as well as inhibition of arachidonic acid (AA) release.
      On the 21st day in vitro, cultures of rat astrocytes were subjected to ischemia
      simulating conditions (combined oxygen glucose deprivation) for 8 h and exposed
      to FK506 (10 - 1,000 nM) and CsA (0.25 - 10 microM). Obtained data suggest the
      cross-talk between the action of 0.25 - 10 microM CsA as well as 1 microM FK506
      on calcineurin (CaN) and cPLA(2) in anti-apoptotic signal transduction pathways.
      Moreover, we have shown that immunosuppressants at these concentrations protected
      glial cells against ischemia-induced apoptosis through the increase of cell
      viability, mitochondrial function restoration, and attenuation of oxidative
      stress. Finally, in our study, low concentrations of FK506 (10 and 100 nM)
      exerted limited effects on the assessed parameters. Our findings document a key
      role either for CaN or cPLA(2) expression attenuation and AA release inhibition
      in the antiapoptotic effect of FK506 and CsA in ischemic astrocytes.

PMID- 16990702
TI  - Effects of treatment for diabetes mellitus on circulating vascular progenitor
      cells.
AB  - The circulating endothelial progenitor cells (EPCs) have an important role in
      angiogenesis, and the smooth muscle progenitor cells (SMPCs) participate in
      atherosclerosis. However, little is known about the effects of treatment of
      diabetes mellitus (DM) on EPCs and SMPCs. Therefore, we investigated the
      relations between the number of circulating vasucular progenitor cells before and
      after the treatment for DM. Ten previously untreated DM patients were enrolled in
      this study. Blood samples were collected before and after treatment. The
      peripheral mononuclear cells were purified and cultured to differentiate them
      into EPCs and SMPCs. After two weeks, the number of EPCs was determined by Dil
      labeled acetylated low density lipoprotein and lectin binding. The number of
      SMPCs was evaluated by immunocytochemical staining of alpha-smooth muscle actin.
      Before treatment, the number of EPCs and SMPCs was significantly related to
      hemoglobin A1c and blood sugar. Serial examination revealed that improvement of
      glycemic control significantly increased the number of both EPCs and SMPCs. DM
      reduces the number of circulating EPCs and SMPCs according to its severity, and
      treatment of DM significantly increases the number of EPCs and SMPCs, which may
      be involved in angiogenesis and atherosclerosis in diabetes.

PMID- 16990703
TI  - Calcium and reactive oxygen species mediated Zn2+ -induced apoptosis in PC12
      cells.
AB  - The release of excessive Zn(2+) from presynaptic boutons into extracellular
      regions contributes to neuronal apoptotic events, which result in neuronal cell
      death. However, the mechanisms of Zn(2+)-induced neuronal cell death are still
      unclear. Therefore, we investigated the dynamics of intracellular Zn(2+),
      calcium, and reactive oxygen species in PC12 cells. The addition of Zn(2+)
      produced cell death in a concentration- and time-dependent manner. (45)Ca(2+)
      influx occurred just after the treatment with Zn(2+), although subsequent
      hydroxyl radical ((*)OH) production did not begin until 3 h after Zn(2+)
      exposure. (*)OH production was significantly attenuated in Ca(2+)-free medium or
      by L-type Ca(2+) channel antagonist treatment, but it was independent of the
      intracellular Zn(2+) content. Dantrolene treatment had no protective effects
      against Zn(2+)-induced cell death. Treatment with N-acetyl-L-cysteine blocked
      (*)OH generation and subsequent cell death. These data indicate that Ca(2+)
      influx and subsequent (*)OH production are critical events in Zn(2+)-induced
      toxicity in PC12 cells.

PMID- 16990704
TI  - Combined treatment of ionizing radiation with genistein on cervical cancer HeLa
      cells.
AB  - The anticancer agent genistein inhibits cell growth of tumor cell lines from
      various malignancies. In our study, we investigated the effectiveness of combined
      treatment of ionizing radiation (IR) with genistein on cervical HeLa cells and
      its possible mechanism. It was found that the inhibitory rate in cells with
      combined treatment was significantly higher than that of the cells treated with
      IR or genistein alone. After treatments of IR (4 Gy) combined with genistein (40
      micromol/L), the apoptotic index of the cells was significantly increased and the
      cells were arrested in the G2/M phase. Survivin mRNA expression increased after
      IR (4 Gy), while it significantly decreased after combined treatment. These
      findings indicated that genistein enhanced the radiosensitivity of cervical
      cancer HeLa cells, and the mechanisms for this action might include increase of
      apoptosis, decrease of survivin expression, and prolongation of cell cycle
      arrest.

PMID- 16990705
TI  - Recent advances in the pathology and classification of ovarian germ cell tumors.
AB  - In recent years, our knowledge of ovarian germ cell tumors has increased, and
      their classification has evolved. The introduction of cisplatin-based
      chemotherapy and the discovery of tumor markers, including alpha-fetoprotein and
      human chorionic gonadotropin, have dramatically changed the clinical outlook for
      most of these patients. In this review, recent advances in the classification and
      pathology of ovarian germ cell tumors are discussed. Where appropriate,
      comparisons are made with testicular germ cell tumors. The last section of the
      article discusses the pathogenesis of germ cell tumors. This review will
      emphasize the articles written in the last 10 years and those that have
      significantly advanced our knowledge of germ cell tumors in past decades.

PMID- 16990706
TI  - Primary malignant melanoma of the ovary: a report of 9 definite or probable cases
      with emphasis on their morphologic diversity and mimicry of other primary and
      secondary ovarian neoplasms.
AB  - Most malignant melanomas encountered in the ovary are metastatic, and the recent
      literature has focused on such neoplasms. Primary tumors are rare with most
      reports being only of single cases. When the tumor is associated with
      teratomatous elements from which it arises, not only is the diagnosis of melanoma
      much more likely to be made but also is a primary nature proven. However,
      although all the primary tumors likely are of teratomatous origin, evidence of
      such an origin may be effaced resulting in problems both in identifying the tumor
      as melanoma and in determining if it is primary or not. In this report, we
      describe 9 primary or probably primary ovarian melanomas and explore the varied
      problems the cases posed. The patients ranged from 18 to 72 years. The tumors,
      all of which were unilateral, ranged from 4 to 23 cm; only 2 were black. In 6
      cases, there was an associated dermoid cyst or monodermal teratoma (struma
      ovarii), 5 in the ipsilateral and 1 in the contralateral ovary. The tumors were
      variously composed of large epithelioid cells with eosinophilic cytoplasm, small
      cells, spindle-shaped cells, or a combination, and in 5 cases, melanin pigment
      (Masson Fontana positive) was identified. In all cases, most of the tumor cells
      had prominent nucleoli. All neoplasms had a predominantly diffuse growth pattern
      with a focal nested architecture in 3 cases. Other noteworthy morphological
      features were tumor giant cells with wreath-like nuclei (4 cases), signet ring
      cells (1 case), clear cells (1 case), intranuclear pseudoinclusions (2 cases), a
      focally myxoid stroma (2 cases), a pseudopapillary appearance caused by
      degeneration (2 cases), and follicle-like structures (3 cases). In 1 case in a 21
      year-old, there was associated hypercalcemia, and focally, the neoplasm, which
      contained follicle-like structures, resembled small cell carcinoma of the
      hypercalcemic type. All cases tested by immunohistochemistry were positive with 1
      or more melanocytic markers, and electron microscopy performed in 3 cases
      revealed intracytoplasmic melanosomes or premelanosomes. The wide differential
      potentially includes neoplasms within most of the categories of primary ovarian
      neoplasia, as well as metastatic melanoma, and is facilitated by thorough
      sampling to identify teratomatous elements, by awareness of the spectrum of
      melanoma in the ovary, and by positivity with melanocytic markers. This is an
      area where electron microscopy can still also contribute useful information.

PMID- 16990707
TI  - Expression of claudins 1, 4, 5, and 7 in ovarian tumors of diverse types.
AB  - In this study, 60 different types of ovarian lesions, mainly consisting of
      ovarian neoplasms, were studied for the expression of claudins 1, 4, 5, and 7.
      Strong expression of claudins 1, 4, and 7 was seen in benign and malignant
      epithelial ovarian tumors. Expression of claudin 5, reported to be mainly present
      in endothelial cells, was seen in ovarian epithelial tumors, but with a
      significantly lower frequency than claudins 1, 4, and 7. On the contrary, sex
      cord stromal tumors and cysts, such as fibromas/thecomas, Sertoli-Leydig cell
      tumors, granulosa cell tumors, and follicular and luteinized cysts were mainly
      negative for claudins 1, 4, 5, and 7. Interestingly, adenomatoid tumors did not
      express claudin 5, which is in agreement with their non-endothelial nature. They
      were also negative for claudin 4, but expressed claudins 1 and 7, but to a lesser
      degree than epithelial lesions. In immature teratomas, the epithelial component
      was usually positive whereas other components were negative for these claudins.
      Dysgerminomas did not express any of the claudins studied. The results show that
      claudins 1, 4, and 7 are mainly expressed in ovarian epithelial tumors and can
      thus be used to indicate epithelial differentiation in them. Eventhough
      considered an endothelial marker, claudin 5 was also present in a subset of
      epithelial lesions. However, this claudin can be used to differentiate
      adenomatoid tumors from vascular lesions. No significant difference was seen
      between epithelial benign and malignant lesions, except for claudin 5, which
      seemed stronger in malignant epithelial tumors.

PMID- 16990708
TI  - Ovarian serous cystadenofibroma with stromal sex cord elements: report of a
      unique case.
AB  - This report describes an ovarian serous cystadenofibroma, in a postmenopausal
      woman, which exhibited extensive sex cord differentiation, in the form of solid
      and hollow tubules resembling Sertoli cell elements, within the stroma. The sex
      cord elements, which were located just beneath the epithelium, were positive with
      both alpha inhibin and calretinin and negative with epithelial membrane antigen.
      They were also CD56 positive but negative with other neuroendocrine markers. True
      sex cord structures or sex cord-like elements have been described in ovarian
      adenosarcomas and pure stromal tumors, especially fibromas. However, as far as we
      are aware, these elements have not been reported in a serous cystadenofibroma.
      The endometrium exhibited simple hyperplasia, perhaps secondary to estrogenic
      activity of the sex cord elements. We discuss the significance of CD56 positivity
      of the sex cord elements.

PMID- 16990709
TI  - Pseudomyxoma peritonei associated with a mucinous ovarian tumor arising from a
      mature cystic teratoma. A case report.
AB  - It has generally been accepted that pseudomyxoma peritonei/disseminated
      peritoneal adenomucinosis originates from appendiceal low-grade adenomatous
      mucinous tumors. A woman who underwent an appendectomy 42 years ago, presented
      with a unilateral ovarian tumor whose immunohistochemical phenotype and its
      association with a teratoma, strongly suggest that pseudomyxoma peritonei
      originated from a ruptured mucinous tumour arising from a mature cystic teratoma.

PMID- 16990710
TI  - Endometrioid cystadenofibroma of the ovary with pelvic lymph node involvement.

PMID- 16990711
TI  - Pathogenesis of balls in mature ovarian cystic teratoma. Report of 3 cases and
      review of literature.
AB  - Ovarian cystic teratomas with intracystic balls are rare, and only 11 cases have
      been reported since 1946. We present 2 new cases and review the literature for
      the clinical presentation and morphological appearances of the cysts and balls.
      We also present our histology findings on a third case reported in the
      international literature. The pathogenesis of balls formation is unknown. We put
      forward a hypothesis based on the forces which control the production and
      absorption of the intracystic contents and also recommendations for investigators
      who may encounter this lesion. We believe that predominance of large secretory
      and absorptive rather than exfoliative surfaces lining the cysts would favor the
      absorption of most of the contents into the general circulation, leaving the
      remaining material to solidify and mould into balls. Still, however, there are
      many unanswered questions.

PMID- 16990712
TI  - Expression of the proliferation marker Ki-67 and of p53 tumor protein in
      trophoblastic tissue of preeclamptic, HELLP, and intrauterine growth-restricted
      pregnancies.
AB  - The human placenta owns the biochemical machinery to proliferate throughout
      gestation. The aim of this study was to investigate the expression of the
      proliferation marker Ki-67 in trophoblastic tissue of intrauterine growth
      retarded (IUGR) placentas, preeclamptic, HELLP, and in normal trophoblastic
      tissue. Slides of paraffin-embedded trophoblastic tissue of patients with IUGR,
      preeclamptic patients, HELLP patients, and normal term placentas were incubated
      with monoclonal antibodies against Ki-67 and p53. Staining reaction was performed
      with the ABC reagent. Intensity of immunohistochemical reaction on the slides was
      analyzed using a semiquantitative score. Identification of Ki-67-expressing cells
      was done by immunofluorescence double staining with Ki-67 and cytokeratin
      antibodies. Expression of Ki-67 and p53 are significantly elevated in
      cytotrophoblastic cells of placentas with HELLP as investigated by
      immunohistochemistry and double immunofluorescence. However, preeclamptic
      cytotrophoblastic tissue on the other hand showed no significantly different
      expression intensity of Ki-67 compared with normal placental tissue controls and
      no changes in p53 expression compared with controls. In IUGR cytotrophoblastic
      cells, we found no statistically significant change in Ki-67 expression but a
      statistically significant down-regulation of p53. An elevated proliferation of
      cytotrophoblastic cells seems to be related to HELLP, and this enhanced
      proliferation seems to be controlled by p53.

PMID- 16990713
TI  - Uterine adenomyoma: a clinicopathologic review of 26 cases and a review of the
      literature.
AB  - The aim of this study is to highlight the importance of diagnosing uterine
      adenomyoma and help in differentiating it from other sinister lesions. Adenomyoma
      of the uterus is a circumscribed nodular aggregate of benign endometrial glands
      surrounded by endometrial stroma with leiomyomatous smooth muscle bordering the
      endometrial stromal component. It may be located within the myometrium, or it may
      involve or originate in the endometrium and grow as a polyp. A retrospective
      analysis of 26 consecutive cases of uterine adenomyomas diagnosed in the
      Department of Pathology, Government Medical College, Chandigarh from January 1994
      to December 2004 was done, and their clinical and histological features were
      analyzed. The criterion used for case identification was a circumscribed mass
      composed of benign endometrial glands with a stromal component consisting of
      endometrial type stroma surrounded by leiomyomatous smooth muscle. Mitotic
      figures were counted within 50 high-power fields (hpf) and recorded as the
      highest number per 10 hpf. The age of the patients ranged from 22 to 60 years
      (mean age, 41 years). The most common presenting symptom was abnormal vaginal
      bleeding (n = 15). Thirteen patients underwent panhysterectomy; 7, total
      hysterectomy; 1, subtotal hysterectomy; 4, polypectomy or tumor removal; and 1,
      curettage. Of the 26 cases of adenomyoma, 24 were in the corpus, 1 was in the
      cervix, and 1 was in the broad ligament. An associated leiomyoma was noted in 12
      cases (46.9%). The adenomyomas were firm in consistency and, on cut section,
      showed a gray-white surface. Five tumors showed cystic spaces filled with dark
      brown material. On microscopic examination, the tumors were well demarcated from
      the surrounding structures. The endometrial glands were mostly tubular and showed
      relatively regular spacing from each other without any back-to-back arrangement.
      The glands were lined by benign proliferative pseudostratified columnar
      epithelium. An occasional typical mitotic figure was noted in these glands in a
      few cases. The glands were surrounded by endometrial stroma which was compact and
      spindly. This stroma was, in turn, bordered by leiomyomatous smooth muscle. Thick
      walled blood vessels were commonly observed. One to two typical mitotic figures
      per 10 hpf were noted in the endometrial stroma in few cases; however, no mitosis
      was noted in the myometrial component. Associated adenomyosis was also noted in 8
      cases (30.8%). Adenomyomas have to be distinguished from a number of other
      lesions, for example, adenomyosis, leiomyoma with entrapped glands, atypical
      polypoid adenomyoma, endometrial polyps, adenofibroma, and adenosarcoma. This
      study highlights the importance of correctly identifying this fairly common
      entity and helps to distinguish adenomyoma from other similar appearing benign
      and malignant lesions.

PMID- 16990714
TI  - Persistent gestational trophoblastic disease after an androgenetic/biparental
      fetal chimera: a case report and review.
AB  - We present a case of a dichorionic/diamniotic twin pregnancy in which one twin
      presented with ultrasound findings suggestive of molar changes in the placenta.
      The placenta of twin A seemed to be grossly enlarged and cystic, and twin A was
      small for gestation. After an inevitable abortion, a detailed histological and
      genetic evaluation was performed on the fetus and placenta from twin A, including
      traditional cytogenetic techniques, microsatellite marker analysis, fluorescent
      in situ hybridization, and p57 immunostaining. It was determined that twin A was
      a chimera with a biparental XX cell line and an androgenetic XY cell line. The 2
      cell lines were present in both the placenta and the fetus. The patient later
      developed and was treated for persistent gestational trophoblastic disease, which
      has been shown to have an increased risk after an androgenetic conception. Cases
      of mosaicism or chimerism involving an androgenetic cell line may be difficult to
      diagnose histologically but are critical to identify because of the increased
      risk for persistent gestational trophoblastic disease. Therefore, we emphasize
      the importance of using multiple molecular, cytogenetic, and immunohistochemical
      techniques when diagnosing cases involving such unusual placental abnormalities.
      To our knowledge, this is the first reported case of persistent gestational
      disease after a fetal chimera.

PMID- 16990715
TI  - Primitive neuroectodermal tumor of the uterus: a case report and review of
      literature.
AB  - A case of primitive neuroectodermal tumor arising in the uterine corpus of a 43
      year-old woman is presented. The tumor mass was 13.3 cm and extended to the
      uterine serosa, endocervical stroma, and left adnexa. Histologically, the tumor
      was composed of small blue cells with scant cytoplasm, indistinct cell borders,
      hyperchromatic round nuclei, and inconspicuous nucleoli focally forming
      pseudorosettes, suggestive of neuroectodermal origin. The tumor cells displayed
      strong immunoreactivity for CD99 and FLI1. Cytogenetic fluorescence in situ
      hybridization study revealed presence of an EWS-FLI1 fusion gene. To the best of
      our knowledge, this is the first case of primitive neuroectodermal tumor of the
      uterus with diagnosis confirmed by FLI1 immunohistochemical labeling and
      demonstration of t (11; 22) by fluorescence in situ hybridization.

PMID- 16990716
TI  - Transitional cell carcinoma of the endometrium: a case report and review of the
      literature.
AB  - We report a case of primary transitional cell carcinoma of the endometrium and
      review the literature which reveals only 12 cases described to date. The patient
      presented with postmenopausal bleeding, and there were no distinctive clinical
      features. An endometrial sample taken at hysteroscopy was reported as a poorly
      differentiated, papillary, nonserous carcinoma with probable squamous metaplasia.
      The tumor removed at hysterectomy and bilateral salpingo-oophorectomy was almost
      all transitional cell with small areas of endometrioid, glandular
      differentiation. Immunohistochemistry demonstrated a similar immunoprofile to
      endometrioid carcinoma of the endometrium and different from reported cases of
      transitional cell carcinoma of the ovary and of the urinary tract.

PMID- 16990717
TI  - Over-expression of topoisomerase IIalpha is related to the grade of cervical
      intraepithelial neoplasia (CIN) and high-risk human papillomavirus (HPV), but
      does not predict prognosis in cervical cancer or HPV clearance after cone
      treatment.
AB  - OBJECTIVE: One of the pathways leading to cervical cancer is a loss of normal
      cell cycle control. Topoisomerase IIalpha and IIbeta are important nuclear
      proteins controlling the G2/M checkpoint, and shown to be over-expressed in many
      human cancers. Their links to oncogenic human papillomavirus (HPV) types and
      their prognostic value in cervical cancer are practically unexplored. MATERIAL
      AND METHODS: As part of our HPV-PathogenISS study, a series of 150 squamous cell
      carcinomas (SCC) and 152 CIN lesions were examined using immunohistochemical
      (IHC) staining for topoisomerase IIalpha (topo IIalpha), and tested for HPV using
      PCR with three primer sets (MY09/11, GP5/GP6, SPF). Follow-up data were available
      from all SCC patients, and 67 CIN lesions had been monitored with serial PCR for
      HPV clearance/persistence after cone treatment. RESULTS: Topo IIalpha expression
      increased with increasing grade of CIN (p = 0.0001), with the most dramatic up
      regulation upon progression from CIN2 to CIN3 and peaking in SCC (OR 16.23; 95%CI
      7.89-33.38). Topo IIalpha up-regulation was also significantly associated with HR
      HPV detection in univariate analysis (OR = 3.07; 95%CI 1.70-5.52), but was
      confounded by the histological grade (Mantel-Haenszel common OR = 1.622; 95%CI
      0.782-3.365), and by entering both p16(INK4a) (9) and Survivin (33) in the
      multivariate regression model. Topo IIalpha did not predict clearance/persistence
      of HR-HPV after treatment of CIN, and it was not a prognostic factor in cervical
      cancer in either univariate or multivariate analysis. CONCLUSIONS: Over
      expression of topo IIalpha is significantly associated with progression from CIN2
      to CIN3, being a late marker of cell proliferation. Its close association with HR
      HPV is plausibly explained by the fact that E7 oncoproteins of these HR-HPV (but
      not LR-HPV) block the normal pRb-mediated inhibition of topo IIalpha by degrading
      the wild-type Rb.

PMID- 16990718
TI  - Variants of human papillomavirus types 16 and 18: histological findings in women
      referred for atypical glandular cells or adenocarcinoma in situ in cervical
      smear.
AB  - Human papillomavirus (HPV) genotypes cannot fully explain the histological
      diagnosis of women with glandular abnormalities detected by cervical smear. Thus,
      this study was designed to analyze the distribution of HPV-16 and HPV-18 variants
      in women referred because of atypical glandular cells and adenocarcinoma in situ
      in their cervical smears and its association with histological results. Twenty
      four women with HPV-16 and 6 with HPV-18, selected from 160 women with cervical
      smears suggestive of glandular abnormalities, were included. Histological results
      showed cervicitis (1 case), squamous neoplasia (18 cases), glandular neoplasia (7
      cases), and glandular neoplasia associated with a squamous component (4 cases).
      Among the 24 cases presenting HPV-16, the European variant was detected in 15
      (62%) and the Asian American in 9 (38%). Among the 15 cases associated with the
      European variant, 14 (93%) presented squamous neoplasia and 1 (7%) invasive
      adenocarcinoma. Asian-American HPV-16 variants were significantly associated with
      histological diagnosis of glandular neoplasia alone (odds ratio, 9.3 [1.4-60.2])
      or associated with squamous neoplasia (odds ratio, 18.7 [1.5-232.3]).
      Adenocarcinomas were detected in 4 of 6 HPV-18-positive cases, being 2 cases had
      the European variant, 1 had the Asian Amerindian variant, and 1 had the African
      variant. The association of HPV-16 with squamous or glandular neoplasia is
      explained by its variants. In this study, squamous neoplasia was related to the
      European variant of HPV-16, whereas glandular neoplasia was related to the Asian
      American variant. Glandular neoplasia is associated with HPV-18, but the results
      of our analysis of its variants were inconclusive.

PMID- 16990719
TI  - Human papillomavirus type distribution in cervical cancer in Delhi, India.
AB  - This hospital-based study in New Delhi, North India was performed to evaluate the
      prevalence of human papillomavirus (HPV) in cases of invasive cervical carcinoma
      (ICC). A total of 10 cases presenting with an obvious cervical growth were
      included in this study. 108 cases that was shown to be ICC on histology (101
      squamous cell carcinomas, 4 adenocarcinomas, and one neuroendocrine carcinoma)
      were included in the analysis. DNA was extracted from tumor tissue and HPV
      genotype was determined by a consensus PCR assay using a reverse line blot
      hybridization assay. Of 106 evaluable cases, 104 (98.1%) were positive for HPV
      infection. Twelve different high-risk HPV types were found. There were 125
      infections, 119 of which were high risk. Six cases had associated low risk
      infections. HPV 16 was the commonest type, seen in 73.6% cases followed by HPV 18
      (14.2%) and 45 (11.3%). A vaccine with 100% efficacy in prevention of HPV 16 and
      18 infections would theoretically reduce the total cancer burden in New Delhi by
      more than 75% (assuming 100% coverage). Increasing the genotype spectrum (e.g.
      valency) if the existing vaccines would be expected to have only a modest impact
      on the potential for cervical protection.

PMID- 16990720
TI  - HMGA2 rearrangement in a case of vulvar aggressive angiomyxoma.
AB  - The histogenesis of aggressive angiomyxoma, an uncommon mesenchymal neoplasm of
      the vulvar, pelvic, and perineal soft tissues, is poorly understood, although the
      neoplastic cells exhibit a myofibroblastic phenotype. Cytogenetic studies of
      aggressive angiomyxoma are scarce; however, a nonrandom involvement of the 12q15
      region where the high mobility group (HMG) protein HMGA2, an architectural
      transcription factor expressed primarily during embryogenesis, is located has
      been suggested. HMGA2 involvement has also been described in a variety of benign
      gynecologic mesenchymal neoplasms. We report an additional case of HMGA2
      rearrangement in vulvar aggressive angiomyxoma, using fluorescence in situ
      hybridization.

PMID- 16990721
TI  - p16, p14, p53, and Cyclin D1 expression and HPV analysis in small cell carcinomas
      of the uterine cervix by Horn et al.

PMID- 16990722
TI  - Intramedullary nailing of proximal quarter tibial fractures.
AB  - OBJECTIVE: To report the results of intramedullary nailing of proximal quarter
      tibial fractures with special emphasis on techniques of reduction. DESIGN:
      Retrospective clinical study. SETTING: Level 1 trauma center. PATIENTS: During a
      36-month period, 456 patients with fractures of the tibial shaft (OTA type 42) or
      proximal tibial metaphysis (OTA type 41A2, 41A3, and 41C2) were treated
      operatively at a level 1 trauma center. Thirty-five patients with 37 fractures
      were treated primarily with intramedullary nailing of their proximal quarter
      tibial fractures and formed the study group. Thirteen fractures (35.1%) were open
      and 22 fractures (59.5%) had segmental comminution. Three fractures had proximal
      intraarticular extensions. MAIN OUTCOME MEASUREMENTS: Alignment and reduction
      postoperatively and at healing. An angular malreduction was defined as greater
      than 5 degrees in any plane. RESULTS: Fractures extended proximally to an average
      of 17% of the tibial length (range, 4% to 25%). The average distance from the
      proximal articular surface to the fracture was 67.8 mm (range, 17 mm to 102 mm,
      not corrected for distance magnification, included for preoperative planning
      purposes only). Postoperative angulation was satisfactory (average coronal and
      sagittal plane deformity of less than 1 degree) as was the final angulation.
      Acceptable alignment was obtained in 34 of 37 fractures (91.9%). Two patients had
      5-degree coronal plane deformities (one varus and one valgus), and 1 patient had
      a 7-degree varus deformity. Two patients with open fractures with associated bone
      loss underwent a planned, staged iliac crest autograft procedure postoperatively.
      Four patients were lost to follow-up. In the remaining 31 patients with 33
      fractures, the proximal tibial fractures united without additional procedures. No
      patient had any change in alignment at final radiographic evaluation. Secondary
      procedures to obtain union at the distal fracture in segmental injuries included
      dynamizations (n = 3) and exchange nailing (n = 1). Complications included deep
      infections in 2 patients that were successfully treated. CONCLUSIONS: Multiple
      techniques were required to obtain and maintain reduction prior to nailing and
      included attention to the proper starting point, the use of unicortical plates,
      and the use of a femoral distractor applied to the tibia. Simple articular
      fractures and extensions were not a contraindication to intramedullary fixation.
      The proximal tibial fracture healed despite open manipulations. Short plate
      fixations to maintain this difficult reduction, either temporary or permanent,
      were effective.

PMID- 16990723
TI  - Comparison of a technique using a new percutaneous osteosynthesis device with
      conventional open surgery for displaced patella fractures in a randomized
      controlled trial.
AB  - OBJECTIVE: To compare the percutaneous patellar osteosynthesis system (PPOS)
      technique with open surgery for patella fractures. DESIGN: Randomized controlled
      trial. SETTING: Referral orthopedic and trauma center. PATIENTS: Fifty-three
      patients with displaced patellar fractures. INTERVENTION: Stabilization and
      fixation of patellar fractures with PPOS or open surgery. MAIN OUTCOME
      MEASUREMENTS: Knee-flexion and -extension angles, pain, surgical time, and
      assessment of knee function based on the Knee Society Clinical Rating Scale
      (KSCRS). RESULTS: Comparison of PPOS and open-surgery groups at 4 weeks showed
      the following: pain, 3.7 +/- 1.6 versus 6.2 +/- 1.4 arbitrary units, P < 0.001;
      flexion angle, 46 +/- 20.7 versus 12.7 +/- 6.0 degrees, P < 0.001; extension
      angle, -2.5 versus -3.8 degrees, P < 0.001. At 8 weeks, the following was
      demonstrated: pain, 1.3 +/- 1.6 versus 4.1 +/- 2.1 arbitrary units, P < 0.001;
      flexion angle, 87 +/- 17.3 versus 34 +/- 26 degrees, P < 0.001; extension angle,
      0 versus -3 degrees, P < 0.001. Surgical time was 35.3 +/- 7.8 versus 66.2 +/-
      14.1 minutes, P < 0.001. KSCRS assessment was 84 +/- 4 versus 70 +/- 8, P < 0.001
      at 8 weeks; 85 +/- 2 versus 73 +/- 8, P < 0.001 at 12 months; and 85 +/- 1 versus
      82 +/- 7, P = 0.246 at 24 months. Frequency of total complications (infections,
      fragment displacement, and wire-related pain) was significantly lower in the PPOS
      than in the open-surgery group (P < 0.02). CONCLUSIONS: PPOS for patella
      fractures was associated with shorter surgical time, less pain, better mobility
      angles, higher functional score up to 2 years, and a lower incidence of
      complications than open surgery.

PMID- 16990724
TI  - Tibial plafond fractures treated by articulated external fixation: a randomized
      trial of postoperative motion versus nonmotion.
AB  - OBJECTIVES: Assess whether postoperative ankle motion after fixation of a
      fracture of the tibial plafond, treated with articulated external fixation, leads
      to a better outcome when compared with similar treatment without postoperative
      ankle motion. DESIGN: Multicenter randomized trial. SETTING: Three Level I trauma
      centers. PATIENTS/PARTICIPANTS: Fifty-five patients were enrolled and entered
      into a Web-based database and randomized into 1 of 2 groups. Forty-one patients
      were evaluated at a 1-year follow-up visit, and 31 were seen at 2 years or longer
      after injury. INTERVENTION: Patients were treated with a hinged external fixator
      and limited internal fixation of the articular surface. They were divided
      postoperatively into two groups, 1 of which had a locked hinge and the other had
      a mobile hinge and a motion protocol. MAIN OUTCOME MEASUREMENTS: A general health
      status questionnaire, the SF-36 (short-form 36); a joint-specific ankle
      questionnaire, the Ankle Osteoarthritis Score (AOS); and range of motion (ROM) of
      the ankle joint. RESULTS: There were no significant differences between the two
      groups at either follow-up interval in the ankle ROM measurement, the AOS pain
      and disability scale, or the SF-36 physical component summary (PCS) and mental
      component summary (MCS) scales. CONCLUSIONS: These results indicate that
      treatment protocols that use long periods of cross-joint external fixation that
      immobilizes the ankle as definitive treatment result in similar patient outcomes
      compared to otherwise identical treatment protocols that incorporate and use an
      articulated hinge for ankle motion. However, the results should be interpreted
      with caution because the patient numbers were too small to detect potentially
      meaningful differences in outcomes and the follow-up was too short to assess for
      differences in the development of arthrosis.

PMID- 16990725
TI  - The effect of plate rotation on the stiffness of femoral LISS: a mechanical
      study.
AB  - OBJECTIVE: Malposition of the femoral Less Invasive Stabilization System (LISS)
      plate may alter its biomechanical behavior. This study compares the mechanical
      stability of "correctly" affixed LISS plates matching the slope of the lateral
      femoral condyle to "incorrectly" placed LISS plates fixed in external rotation
      relative to the distal femur. METHODS: A fracture gap model was created to
      simulate a comminuted supracondylar femur fracture (AO/OTA33-A3). Fixation was
      achieved using two different plate positions: the LISS plate was either placed
      "correctly" by internally rotating the plate to match the slope of the lateral
      femoral condyle, or "incorrectly" by externally rotating the plate relative to
      the distal femur. Following fixation, the constructs were loaded in axial,
      torsional, and cyclical axial modes in a material testing machine. MAIN OUTCOME
      MEASUREMENT: Stiffness in axial and torsional loading; total deformation and
      irreversible (plastic) deformation in cyclical axial loading. RESULTS: The mean
      axial stiffness for the correctly placed LISS constructs was 21.5% greater than
      the externally rotated LISS constructs (62.7 N/mm vs. 49.3 N/mm; P = 0.0007). No
      significant difference was found in torsional stiffness between the two groups.
      Cyclical axial loading caused significantly less (P < 0.0001) plastic deformation
      in the correct group (0.6 mm) compared with externally rotated group (1.3 mm).
      All the constructs in the incorrect group failed, where failure was defined as a
      complete closure of the medial fracture gap, prior to completion of the test
      cycles. CONCLUSION: Correct positioning of the LISS plate for fixation of distal
      femur fractures results in improved mechanical stability as reflected by an
      increased stiffness in axial loading and decreased plastic deformation at the
      bone-screw interface.

PMID- 16990726
TI  - Biomechanical analysis of blade plate versus locking plate fixation for a
      proximal humerus fracture: comparison using cadaveric and synthetic humeri.
AB  - OBJECTIVE: To compare the mechanical stability of a fixed-angle blade plate with
      that of a locking plate in a cadaveric proximal humerus fracture-fixation model
      subjected to cyclic loading. A secondary objective was to evaluate whether the
      use of synthetic humerus specimens would replicate significant differences found
      during cadaveric tests. DESIGN: Mechanical evaluation of constructs in bending
      and torsion. SETTING: Biomechanical laboratory in an academic medical center.
      METHODS: Simulated humeral neck fractures (Orthopaedic Trauma Association (OTA)
      classification 11A3), in matched-pair cadaveric and synthetic specimens underwent
      fixation using either a 3.5-mm, 90-degree cannulated LC-Angled Blade Plate or a
      3.5-mm LCP Proximal Humerus Locking Plate. Cadaveric specimen constructs were
      cyclically loaded in bending and torsion; synthetic specimens were tested in
      torsion. MAIN OUTCOME MEASURE: Humeral shaft-bending displacements and angular
      rotations for respective cyclic bending loads and axial torques were recorded and
      compared at repeated cyclic intervals to evaluate construct loosening. RESULTS:
      Locking-plate constructs exhibited significantly less loosening than blade-plate
      constructs for torsional loading in cadaveric specimens (P = 0.036). The two
      types of constructs performed similarly for torsional loading in synthetic
      specimens (P = 0.100). Under cyclic, closed-bending load conditions in which the
      plates served as tension members, both types of constructs performed similarly in
      cadaveric specimens (P = 0.079). CONCLUSIONS: For simulated humeral neck
      fractures subjected to cyclic loading, locking-plate constructs demonstrated
      significantly greater torsional stability and similar bending stability to blade
      plates in a cadaveric specimen model. In contrast, these same constructs
      performed similarly with torsional loading when using synthetic humerus
      specimens. These results indicate potential advantages for locking-plate
      fixation. They also indicate that the synthetic specimens tested may not be
      appropriate for evaluating fixation stability in the humeral head, where
      cancellous bone fixation predominates.

PMID- 16990727
TI  - Factors associated with outcome after subtalar arthrodesis.
AB  - OBJECTIVES: To evaluate radiographic and functional outcomes after subtalar
      arthrodesis and to identify patient factors associated with poor outcome. DESIGN:
      Retrospective study. SETTING: Two academic hospitals. PATIENTS: Eighty-eight
      patients with primary or secondary osteoarthritis treated between 1995 and 2002.
      INTERVENTION: Primary subtalar arthrodesis. MAIN OUTCOME MEASUREMENTS:
      Radiographic outcome was assessed by determining union rates. Functional outcome
      was assessed through self-administered questionnaires (Short Form-36, Short
      Musculoskeletal Function Assessment, and the AAOS Foot and Ankle Instrument).
      RESULTS: After adjusting for age and sex smokers were 3.8 times more likely to go
      on to nonunion than nonsmokers (P < 0.05). As patients aged, there was a higher
      likelihood of nonunion if they also smoked (P < 0.05). Of patients undergoing
      subtalar bone block distraction arthrodesis 95% went on to union compared with
      65% of patients treated with an in situ subtalar arthrodesis without bone graft
      (P < 0.05). There was a trend for higher rates of union if a bone graft was used
      among patients treated with an in situ subtalar arthrodesis. Diabetic patients
      were 18.7 times more likely to have a malunion (P < 0.05). As a group, patients
      who have undergone subtalar arthrodesis can expect significantly worse functional
      outcomes compared with the Canadian and American normative populations. The
      poorest functional outcomes were observed among patients with diabetes. A trend
      for poorer outcome in bodily pain and general health (Short Form-36) was seen in
      workers' compensation patients. CONCLUSIONS: Certain patient variables are
      associated with poorer outcomes after subtalar fusion. The results of this study
      will enable surgeons to provide better information to patients in preoperative
      discussions with respect to patient expectations, outcomes, and the success of
      surgery.

PMID- 16990728
TI  - Comparison of lateral locking plate and antiglide plate for fixation of distal
      fibular fractures in osteoporotic bone: a biomechanical study.
AB  - OBJECTIVES: The purpose of this study was to compare the biomechanical properties
      of posterolateral antiglide plating and lateral locked plating for fixation of
      displaced short oblique fractures of the fibula in osteoporotic bone. METHODS:
      Short oblique fractures of the distal fibula at the level of the syndesmosis were
      simulated with a fibular osteotomy and ligamentous sectioning in 18 paired fresh
      frozen ankles. The fractures were fixed with either a lateral locking plate with
      an independent lag screw or a posterolateral antiglide plate with a lag screw
      through the plate. The specimens were tested under a torsional load to failure.
      The torque to failure, angular rotation at failure, and construct stiffness of
      the two groups were compared. RESULTS: The torque to failure and construct
      stiffness were significantly greater on the side with the posterolateral
      antiglide plate than on the side with the the lateral locking plate (P = 0.01 and
      0.005, respectively). CONCLUSIONS: The posterolateral antiglide plate
      demonstrated improved biomechanical stability as compared to the lateral locking
      plate in osteoporotic bone. In situations where fixation needs to be optimized,
      use of an antiglide plate may be favored over a lateral locking plate construct.

PMID- 16990730
TI  - Small-incision surgical exposure for select fractures of the acetabulum: the
      gluteus maximus-splitting approach.
AB  - This technique article presents a small-incision, gluteal-splitting approach for
      the treatment of select fractures involving the posterior acetabulum. The
      approach essentially involves the proximal portion of the Kocher-Langenbeck
      incision, and it can be extended to a larger exposure if needed. It is ideally
      suited for posterior-wall fractures, along with select transverse and posterior
      column fractures.

PMID- 16990729
TI  - Validating a newly proposed classification system for thoracolumbar spine trauma:
      looking to the future of the thoracolumbar injury classification and severity
      score.
AB  - BACKGROUND: Although numerous systems have been proposed, there is no universally
      accepted classification or scoring system for thoracolumbar spine injuries. Some
      have gained popularity, but most systems have never been modified or advanced
      beyond their initial introductory state. To the authors' knowledge, no
      thoracolumbar classification system has ever been validated in a systematic and
      scientific manner. STUDY PURPOSE: To critically review previous thoracolumbar
      classification systems, to discuss the proposal of the new Thoracolumbar Injury
      Classification and Severity Score (TLICS), to review the steps taken thus far in
      assessing the reliability of this system, and to discuss plans for future
      clinical validation of TLICS. METHODS: The authors performed a comprehensive
      search and analysis of previously published systems for classifying or scoring
      thoracolumbar spine injuries. Based on the merits and faults of these systems,
      among other factors, they have developed TLICS. CONCLUSIONS: Of the three phases
      of validating a fracture classification system described by Audige et al, TLICS
      has successfully passed through phase 1 (development) and phase 2 (multicenter
      agreement studies). With modifications made in response to phase 2 studies, TLICS
      will be ready to enter into the clinical validation phase. Although TLICS will
      initially be assessed for its ability to predict type of treatment, it is the
      authors' hope that, with appropriate analysis, the system will also be predictive
      of injury severity and clinical outcomes. These qualities remain to be
      demonstrated through rigorous prospective clinical investigation.

PMID- 16990731
TI  - Intraoperative use of the pelvic c-clamp as an aid in reduction for posterior
      sacroiliac fixation.
AB  - Posterior pelvic ring injuries with dissociation of the sacroiliac joint can be a
      therapeutic challenge. Open procedures for reduction have a significant risk for
      wound complications although inadequate reductions using percutaneous methods can
      have poor long-term outcomes. Several indirect reduction methods have been
      previously described for closed reduction of the sacroiliac joint. We present our
      technique for the intraoperative use of the pelvic c-clamp as a reduction aid for
      the posterior pelvis in conjunction with percutaneous iliosacral screw fixation.
      This technique has been used routinely in our patients who sustain injuries to
      the sacroiliac joint and are candidates for closed reduction and percutaneous
      fixation. Our objective is to provide orthopedic surgeons an additional means by
      which to reduce sacroiliac disruptions by percutaneous means.

PMID- 16990732
TI  - Sacral fracture associated with small bowel entrapment: a case report.
AB  - We report the third documented case of small bowel entrapment within a sacral
      fracture leading to small bowel obstruction. This important diagnosis is rare and
      difficult to make, even with current imaging methods. We report a case in which a
      segment of small bowel trapped in a Denis II fracture of the sacrum required
      laparotomy, small bowel resection, and an omental patch over the fracture site.
      In this case the outcome was favorable with no residual sequelae.

PMID- 16990733
TI  - Delayed pseudoaneurysm caused by distal locking screw of a femoral intramedullary
      nail: a case report.
AB  - Interlocked intramedullary nailing is an accepted technique in the management of
      closed femoral shaft fractures. If this technique is used in patients who are
      skeletally immature, the position of locking screws relative to soft tissues can
      alter with time. We present a case of an 11-year-old male who developed a delayed
      pseudoaneurysm 4 years after intramedullary nailing that was most likely produced
      by movement of the distal locking screws of his femoral nail in relation to the
      surrounding vascular structures.

PMID- 16990734
TI  - Ocular myasthenia: diagnosis, treatment, and pathogenesis.
AB  - BACKGROUND: Although myasthenia gravis (MG) is often considered the best
      understood autoimmune disorder and effective treatments have controlled life
      threatening complications, the pathogenesis of ocular myasthenia (OM) remains
      enigmatic, and its clinical consequences offer therapeutic challenges. REVIEW
      SUMMARY: About half of patients with MG present with visual complaints of droopy
      eyelids or double vision, and many will remain with purely ocular muscle weakness
      without generalized weakness, defined as OM. OM may be confused with disorders of
      the brainstem, ocular motor nerves, and eye muscles. Frustrating for the
      clinician, confirmatory tests such as the edrophonium test, serum acetylcholine
      receptor antibodies, and standard electrodiagnostic evaluations may fail to
      positively identify the clinical suspicion of OM. Patients may derive relief from
      nonpharmacologic interventions and cholinesterase inhibitors, but most will
      desire better symptom control with corticosteroids or need other
      immunosuppression. Early corticosteroid therapy may reduce the probability of
      generalization of the disease. The reasons for ocular muscle involvement by OM
      include physiologic and cellular properties of the ocular motor system and the
      unique immunology of OM, which, when better understood, will lead to novel
      treatments. CONCLUSIONS: OM is a challenging disorder for the clinician and
      scientist, with both learning from the other for the betterment of the patient.
      The future requires answers to why the ocular muscles are so frequently involved
      by MG, whether the generalization of the disease may be limited by early
      corticosteroid treatment, and what treatment options may be developed which will
      improve symptoms without long-term complications.

PMID- 16990735
TI  - Parkinson's disease and genetics.
AB  - BACKGROUND: Idiopathic Parkinson disease (IPD) is a condition of unknown cause.
      Several factors are believed to contribute to its onset, and many studies have
      been conducted in search of the possible etiology of Parkinson disease. REVIEW
      SUMMARY: Genetic factors have become relevant when trying to explain the onset of
      Parkinson disease. The studies are divided into 2 categories: epidemiological and
      studies that analyze twins from families with members suffering from Parkinson
      disease, thus looking for the responsible genetic mutations. In this article we
      address this controversial topic, reviewing some of the most significant studies
      trying to provide evidence which relates genetics to Parkinson disease.
      CONCLUSION: We present current epidemiological studies and the most important
      genetic factors related to Parkinson disease, including the latest information
      currently available on each issue.

PMID- 16990736
TI  - Causes of mortality on a university hospital neurology service.
AB  - BACKGROUND: The mortality rate for all patients cared for by inpatient neurology
      services has not been described. METHODS: Quality assurance case discussions of
      all patients (n = 6012) admitted to a neurology service from 1996 to 2003 were
      reviewed to determine frequency and causes of mortality. All cases of mortality
      were reviewed in detail. RESULTS: The majority of patients (98%) survived their
      admission; 118 patients died. In 95/118 cases, care had been withdrawn at the
      time of death. In 11 cases, adverse events occurred during the patients' hospital
      stay and may have impacted outcome. Few patients (18%) had clear advance
      directives. CONCLUSION: Most mortality in this acute care neurology setting
      occurs in the course of stroke, epilepsy, or complicated tumor management and is
      managed through withdrawal of care with family participation.

PMID- 16990737
TI  - Treatment with oxcarbazepine during pregnancy.
AB  - BACKGROUND: Managing epilepsy during pregnancy is a critical challenge as
      maternal seizures may have deleterious effects on the fetus. While many patients
      with epilepsy have been managed successfully with antiepileptic drugs (AEDs), the
      potential teratogenicity of AEDs is a major concern. First-generation AEDs such
      as valproate have been associated with at least a 2-fold risk of fetal
      malformations compared with the general population. However, recent studies
      suggest that the newer AEDs given as monotherapy may have a lower teratogenic
      risk. The current case report adds to the growing experience of oxcarbazepine
      therapy in pregnant women with epilepsy. REVIEW SUMMARY: This case report
      presents a 23-year-old female with a history of complex partial seizures (CPS)
      and mild depression. In high school, she had 2 initial tonic-clonic seizures and
      was placed on phenytoin monotherapy. She was subsequently placed on combination
      therapy (phenytoin + gabapentin) and was maintained on it for several years.
      Preceding a planned pregnancy, the patient was switched to oxcarbazepine and
      tapered off both phenytoin and gabapentin. The patient was maintained on
      oxcarbazepine monotherapy with a seizure-free pregnancy and delivered a normal,
      healthy baby girl. The patient breast-fed the infant for 6 months, supplemented
      with infant formula without any adverse effects. Subsequently, the patient has
      had a healthy second child while receiving oxcarbazepine during her pregnancy.
      CONCLUSION: Although there are very limited data in the literature, this case
      illustrates that a patient with a history of CPS can be treated with
      oxcarbazepine with no adverse effects during and after pregnancy.

PMID- 16990738
TI  - The clinical spectrum of blunt cerebrovascular injury.
AB  - BACKGROUND: Incidence, prevalence, and clinical impact of blunt cerebrovascular
      injury (BCVI) are unknown. There are no standardized recommendations for
      screening. REVIEW SUMMARY: A databank of 306 patients with a history of trauma
      was searched for all subjects with a proven or suspected concomitant BCVI. All
      patients had undergone MRI for the evaluation of traumatic and vascular cerebral
      lesions. The diagnosis of BCVI relies on angiographic and/or ultrasound findings.
      By way of illustration, the case histories of the patients are reported. Eleven
      subjects (3.6%) were identified. In 8 patients (2.6%), the diagnosis of BCVI can
      be regarded as proven; in 3 patients (0.98%), a diagnosis of BCVI is probable.
      The patients could be sorted into the following categories: (i) patients with
      BCVI and early strokes, (ii) patients with BCVI and late strokes, (iii) patients
      with early strokes and no detectable BCVI/vessel abnormality, (iv) patients with
      occult BCVI. Evidence of cerebral ischemia/stroke was present in 9 patients (82%,
      or 2.9% of all patients). In all patients with stroke, it was the major or sole
      cause of disability. CONCLUSIONS: BCVI and BCVI-related strokes are not rare. The
      time window for the development of ischemic complications is highly variable and
      may be longer than is currently assumed. Even if clinically silent, a diagnosis
      of BCVI has medicolegal implications and may influence therapy and prognosis in
      later life. Because of the association of BCVI and motor vehicle accidents,
      screening is suggested in these patients, and ultrasound could be a practical
      tool. Although there is substantial suspicion for BCVI in individual trauma
      patients suffering from stroke, the diagnosis cannot always been proven.

PMID- 16990739
TI  - Does prior aspirin use reduce stroke mortality?
AB  - BACKGROUND: Millions of people around the world regularly consume aspirin, but
      its value in determining stroke severity is still not clear. It has been stated
      that prior aspirin use might reduce the severity of ischemic stroke by reducing
      the size of fibrin-platelet emboli or by ameliorating platelet hyperaggregability
      that occurs in the microcirculation. However there are only few large studies
      focusing on the early outcome of stroke patients including both ischemic stroke
      and primary intracerebral hemorrhage patients with prior aspirin therapy. REVIEW
      SUMMARY: We retrospectively analyzed the medical records of 2509 consecutive
      stroke patients who were hospitalized in the 2nd Neurology Clinic of Haydarpasa
      Numune Education and Research Hospital, Istanbul, Turkey, during the period of
      1993-2003. We compared the early mortality rates in the patients with prior
      aspirin use versus the patients without. Of the patients without prior aspirin
      use, 20.1% died during the first 3 weeks of the stroke, while only 11.5% of the
      patients with prior aspirin use died during the same period. The difference in
      early mortality rate between 2 groups was extremely significant (P = 0.0008).
      Logistic regression analysis indicated that aspirin use was a significant (P <
      0.01) and independent predictor of early stroke mortality. CONCLUSION: Daily low
      dose (100-300 mg) aspirin has a protective effect in reducing the risk of early
      death in stroke.

PMID- 16990740
TI  - What should psychiatry residents be taught about neurology?: A survey of
      psychiatry residency directors.
AB  - OBJECTIVES: To improve our ability to teach psychiatry residents during their
      required 2 months on neurology rotations, we investigated the perceived needs of
      psychiatry program training directors. METHODS: We contacted the program
      directors organization of the American Psychiatric Association and disseminated a
      web-based survey to all program directors. The survey asked questions about the
      format and content of neurology training desired for psychiatry residents. The
      survey was sent a second time to increase response rate. RESULTS: Sixty (32%)
      training directors responded. Overall satisfaction with neurologic education was
      rated at 3.6 out of 5 (standard deviation +/- 0.96). The specific content areas
      which elicited the most interest for focused training modules were differential
      diagnosis and biologic substrates of dementia, evaluation and treatment of drug
      related and spontaneous movement disorders, evaluation and management of sleep
      disorders, cognitive and mood effects of stroke, and inherited disorders. Many
      program directors commented on perceived weaknesses of inpatient-based exposure
      to neurology; 78% of responders favored outpatient and consultation settings.
      CONCLUSIONS: In an era of deliberation about neurobehavioral integration and
      cross-training of neurologists and psychiatrists, neurologists should strive to
      provide the best possible multidisciplinary education to psychiatry trainees.

PMID- 16990741
TI  - Magnetic resonance imaging abnormalities in the corpus callosum of a patient with
      neuropsychiatric lupus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystem autoimmune
      disorder which can present with a variety of neurologic and psychiatric
      complications. Currently, there are no consensus neuroimaging findings associated
      with neuropsychiatric SLE. CASE SUMMARY: We describe the unusual neuroimaging
      findings in a patient with SLE and a history of epilepsy who presented to a
      tertiary care emergency department with features of neuropsychiatric lupus, as
      well as recent seizures. Magnetic resonance imaging of the brain revealed an
      isolated lesion with T2 signal hyperintensity and restricted diffusion in the
      midline splenium of the corpus callosum. CONCLUSIONS: While establishing the
      precise etiology underlying the clinical and radiographic observations in this
      case is difficult, several possibilities are discussed, including acute ischemia
      and epileptic sequelae. The location of the patient's lesion in a region
      potentially associated with pure psychotic disorders raises the possibility that
      such a lesion may be sufficient to produce acute behavior changes and psychotic
      features in certain patients.

PMID- 16990742
TI  - A case of foot drop as an expression of brain metastases?
AB  - Foot drop can be defined as a significant weakness in ankle and toe dorsiflexion.
      Injury to the dorsiflexors or to any point along the neural pathways that supply
      these muscles can result in a foot drop. Injury to the peroneal nerve is usually
      the major precipitant. Other causes vary from trauma to surgical nerve injury, as
      well as leg compartment syndromes or dorsiflexor injuries, peripheral nerve
      injuries, stroke, neuropathies, drug toxicities, spinal stenosis, L5 sciaticas,
      systemic diseases such as connective tissue diseases, vasculidities, or diabetes.
      This report focuses on a patient presenting with a foot drop as an unusual
      manifestation of brain metastasis. His minimal symptomatology seemed to point
      towards a local process. Therefore, early recognition and prompt treatment are
      essential. The central nervous system must be the target of investigations when
      the workup fails to disclose the proper etiology. Potential diagnostic delays may
      occur. Certain cases may require a more aggressive approach.

PMID- 16990743
TI  - Herpes simplex encephalitis: is anticoagulation safe?

PMID- 16990744
TI  - Patient and family fact sheet. Erectile dysfunction.

PMID- 16990745
TI  - Nurses, patients, and community: partnerships in patient safety.

PMID- 16990746
TI  - Patient safety and the nursing shortage: a national concern.

PMID- 16990747
TI  - An overview of the patient safety movement in healthcare.

PMID- 16990749
TI  - Patient safety, elephants, chickens, and mosquitoes.
AB  - Five years after the landmark report by the Institute of Medicine, To Err is
      Human (2000), many of us still grapple with making care safer for patients. This
      article broadly describes how patient safety fits into the picture of quality,
      concepts in patient safety, and practical safety processes you can implement
      today.

PMID- 16990751
TI  - Safely re-integrating silicone breast implants into the plastic surgery practice.
AB  - In the early 1990s, it was reported that silicone breast implants were possibly
      responsible for serious damage to women's health. In January 1992, the Food and
      Drug Administration issued a voluntary breast implant moratorium and, in April,
      issued a ban on the use of silicone gel-filled implants for cosmetic breast
      augmentation. Since that time, silicone gel-filled breast implants have been
      available to women only for select cases: women seeking breast reconstruction or
      revision of an existing breast implant, women who have had breast cancer surgery,
      a severe injury to the breast, a birth defect that affects the breast, or a
      medical condition causing a severe breast deformity. Since the ban on the use of
      silicone gel-filled breast implants for cosmetic breast augmentation, numerous
      scientific studies have been conducted. To ensure patient safety, the American
      Board of Plastic Surgery believes that these scientific studies and the Food and
      Drug Administration's scrutiny of silicone gel-filled breast implants have been
      appropriate and necessary.

PMID- 16990752
TI  - The breast implant story.

PMID- 16990753
TI  - Patient safety through patient education in a charity medical program.
AB  - As perioperative registered nurses, we tend to think of patient safety as
      protection from injury immediately prior to, during, and immediately after
      surgical procedures. However, patient safety extends beyond discharge and is a
      measurement of how effective patient teaching is in attaining desired outcomes.
      This article describes the Fresh Start program, the patient population we serve,
      and our planning cycle. It also describes the use of the "Perioperative Patient
      Focused Model" to deliver care and the relationship between patient education and
      safety. A description of challenges encountered in the clinical setting examines
      their role as critical factors in the education and safety of patients, and
      identifies possible ways to address them.

PMID- 16990754
TI  - Understanding the anatomy when using dermal fillers enhances patient safety.

PMID- 16990756
TI  - Joint Commission on Accreditation of Healthcare Organizations announces 2007
      Patient Safety Goals.

PMID- 16990757
TI  - Patient safety considerations regarding dermal filler injections.
AB  - Today's population is seeking procedures that enhance or improve its appearance,
      that require little or no downtime, and that provide immediate results. Dermal
      filler injections are among the top five procedures performed for this purpose.
      Patient safety must remain the ultimate goal of any practitioner delivering such
      procedures. This column will examine pertinent safety considerations in relation
      to the delivery of dermal filler injections.

PMID- 16990759
TI  - High occurrence of JAK2 V617 mutation in refractory anemia with ringed
      sideroblasts associated with marked thrombocytosis.

PMID- 16990760
TI  - High leucovorin doses during high-dose methotrexate treatment may reduce the cure
      rate in childhood acute lymphoblastic leukemia.
AB  - We explored the relationship between time to relapse and different exposure
      variables (serum methotrexate (S-MTX) 23, 36 and 42 h after start of
      administration, MTX elimination time and leucovorin (LV) dose) during high-dose
      MTX (HDM) treatment of 445 children with acute lymphoblastic leukemia. MTX was
      infused at 5 g/m2 (non-high risk) or 8 g/m2 (high risk) over 24 h, 2-9 times per
      patient. LV rescue dose was adjusted according to the S-MTX concentration. Time
      from end of the last HDM to relapse was analyzed by Cox regression analysis with
      the logarithms of S-MTX and LV dose as exposures. The combined results from all
      risk groups suggest that high LV dose is related to higher risk for relapse.
      Doubling of the LV dose increased the relapse risk by 22% (95% confidence
      interval 1-49%, P = 0.037). High LV doses correlated with high MTX levels at 23,
      36 and 42 h and longer elimination time. The results suggest that high doses of
      LV increase the risk for relapse despite the fact that they were correlated with
      high MTX levels and longer MTX elimination time. The choice of MTX and LV doses
      may be regarded as an intricate balance between effect and counter-effect.

PMID- 16990761
TI  - The history of the angiogenic switch concept.
AB  - Spontaneously arising tumor cells are not usually angiogenic at first. The
      phenotypic switch to angiogenesis is usually accomplished by a substet that
      induces new capillaries that then converge toward the tumor. The switch clearly
      involves more than simple upregulation of angiogenic activity and is thought to
      be the result of a net balance of positive and negative regulators. Tumor growth
      is although to require disruption of this balance and hence this switch must
      turned on for cancer progression. Progenitor endothelial cells, the crosstalk
      between angiogenic factors and their receptors and the interaction between
      vasculogenesis and lymphangiogenesis are all factors that may contribute to the
      switch. Its promotion is also the outcome of genetic instability resulting in the
      emergence of tumor cell lines. This review describes the history of the
      angiogenic switch illustrated in the literature and with particular reference to
      the three transgenic mouse models, namely RIP1-TAG2, keratin-14 (K14) (human
      papilloma virus) HPV16 and papilloma virus, used for stage-specific assessment of
      the effects of antiangiogenic and antitumorigenic agents.

PMID- 16990762
TI  - Hematologic and cytogenetic response to lenalidomide monotherapy in acute myeloid
      leukemia arising from JAK2(V617F) positive, del(5)(q13q33) myelodysplastic
      syndrome.

PMID- 16990763
TI  - Identification of Notch target genes in uncommitted T-cell progenitors: No direct
      induction of a T-cell specific gene program.
AB  - Deregulated Notch signaling occurs in the majority of human T-ALL. During normal
      lymphoid development, activation of the Notch signaling pathway poses a T-cell
      fate on hematopoietic progenitors. However, the transcriptional targets of the
      Notch pathway are largely unknown. We sought to identify Notch target genes by
      inducing Notch signaling in human hematopoietic progenitors using two different
      methods: an intracellular signal through transfection of activated Notch and a
      Notch-receptor dependent signal by interaction with its ligand Delta1. Gene
      expression profiles were generated and evaluated with respect to expression
      profiles of immature thymic subpopulations. We confirmed HES1, NOTCH1 and NRARP
      as Notch target genes, but other reported Notch targets, including the genes for
      Deltex1, pre-T-cell receptor alpha and E2A, were not found to be differentially
      expressed. Remarkably, no induction of T-cell receptor gene rearrangements or
      transcription of known T-cell specific genes was found after activation of the
      Notch pathway. A number of novel Notch target genes, including the transcription
      factor TCFL5 and the HOXA cluster, were identified and functionally tested.
      Apparently, Notch signaling is essential to open the T-cell pathway, but does not
      initiate the T-cell program itself.

PMID- 16990766
TI  - Quantification of marrow CD34+ cells: An important tool for distinguishing
      between hypoplastic myelodysplastic syndromes and aplastic anemia.

PMID- 16990767
TI  - Predictive value of p16 or Rb inactivation in a model of naturally occurring
      canine non-Hodgkin's lymphoma.

PMID- 16990768
TI  - High HSP70-membrane expression on leukemic cells from patients with acute myeloid
      leukemia is associated with a worse prognosis.

PMID- 16990769
TI  - T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet
      optimal functional requirements for adoptive T-cell therapy.
AB  - Adoptive T-cell immunotherapy may provide complementary therapy for childhood B
      cell precursor acute lymphoblastic leukemia (BCP-ALL). In this study, we have
      analyzed the functional characteristics of anti-BCP-ALL effector T cells
      generated by co-culturing T lymphocytes and dendritic cells (DC) from allogeneic
      human stem cell transplantation (HSCT) donors. After 21-day co-culture with DC
      pulsed with CD40L+ apoptotic BCP-ALL blasts, T cells presented with both effector
      and central memory phenotype, and showed high and specific cytotoxic activity
      against leukemic cells (average lysis = 77%), mostly mediated by CD8+ T cells.
      Noticeably, growth of CD4 T cells was maintained (45% of total cells), which
      actively produced Th1 cytokines (IFN-gamma, TNF-alpha, IL-2), but not IL-4, IL-5
      and IL-10. Anti-BCP-ALL T cells expressed CD49d and CXCR4 (implicated in the
      recruitment to bone marrow), and CD62L and CCR7 (involved in the migration to
      lymphoid organs). In accordance with this profile, T cells significantly migrated
      in response to the chemokines CXCL12 and CCL19. In conclusion, stimulation of T
      cells with CD40L+BCP-ALL cells-loaded DC not only elicited the generation of
      potent and specific anti-leukemic cytotoxic effectors, but also the
      differentiation of specific and functional Th-1 CD4 lymphocytes. These effectors
      are fully equipped to reach leukemia-infiltrated tissues and have characteristics
      to support and orchestrate the anti-tumor immune-response.

PMID- 16990770
TI  - Wilms' tumor 1 mutation accumulated during therapy in acute myeloid leukemia:
      Biological and clinical implications.

PMID- 16990771
TI  - Rationale for the recommendations for harmonizing current methodology for
      detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia.
AB  - Molecular monitoring for patients with chronic myeloid leukaemia (CML) has become
      an important practice in the era of imatinib therapy. For successful widespread
      introduction into the mainstream patient monitoring schedule, many procedural
      aspects of the complex real-time quantitative polymerase chain reaction (RQ-PCR)
      technique for measuring BCR-ABL transcripts require optimization. Recommendations
      for harmonizing the differing methodologies have recently been proposed. These
      recommendations were designed to maximize reliability of analysis for clinical
      decision making and proposed the adoption of an International Scale of
      measurement. The purpose of this review is to present the evidence and supporting
      data for specific recommendations. These recommendations include use of the same
      source of cells, either blood or marrow, for analysis; for validation of equal
      PCR amplification efficiencies of cDNA and standards when using a plasmid to
      construct standard curves and for ensuring ongoing high-level performance by
      undertaking a quality assurance programme. Clinicians must know the measurement
      reliability of an RQ-PCR assay to be able to determine the significance of a
      change in BCR-ABL level. An assay with poor precision limits the clinical
      usefulness of results. International harmonization should establish RQ-PCR
      measurement of BCR-ABL as the best method for monitoring treatment response for
      patients with CML.

PMID- 16990772
TI  - The role of microRNAs in normal hematopoiesis and hematopoietic malignancies.
AB  - Over the past few years, it has become evident that microRNAs (miRNAs) play an
      important regulatory role in various biological processes. Much effort has been
      put into the elucidation of their biogenesis, and this has led to the general
      concept that a number of key regulators are shared with the processing machinery
      of small interfering RNAs. Despite the recognition that several miRNAs play
      crucial roles in normal development and in diseases, little is known about their
      exact molecular function and the identity of their target genes. In this review,
      we report on the biological relevance of miRNAs for the differentiation of normal
      hematopoietic cells and on the contribution of deregulated miRNA expression in
      their malignant counterparts.

PMID- 16990773
TI  - Quantitative RT-PCR analysis of sphingolipid metabolic enzymes in acute leukemia
      and myelodysplastic syndromes.

PMID- 16990774
TI  - Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic
      thrombocytopenic purpura is in part due to different forms of cell death.
AB  - Platelet production requires compartmentalized caspase activation within
      megakaryocytes. This eventually results in platelet release in conjunction with
      apoptosis of the remaining megakaryocyte. Recent studies have indicated that in
      low-risk myelodysplastic syndromes (MDS) and idiopathic thrombocytopenic purpura
      (ITP), premature cell death of megakaryocytes may contribute to thrombocytopenia.
      Different cell death patterns have been identified in megakaryocytes in these
      disorders. Growing evidence suggests that, besides apoptosis, necrosis and
      autophagic cell death, may also be programmed. Therefore, programmed cell death
      (PCD) can be classified in apoptosis, a caspase-dependent process, apoptosis
      like, autophagic and necrosis-like PCD, which are predominantly caspase
      independent processes. In MDS, megakaryocytes show features of necrosis-like PCD,
      whereas ITP megakaryocytes demonstrate predominantly characteristics of apoptosis
      like PCD (para-apoptosis). Triggers for these death pathways are largely unknown.
      In MDS, the interaction of Fas/Fas-ligand might be of importance, whereas in ITP
      antiplatelet autoantibodies recognizing common antigens on megakaryocytes and
      platelets might be involved. These findings illustrate that cellular death
      pathways in megakaryocytes are recruited in both physiological and pathological
      settings, and that different forms of cell death can occur in the same cell
      depending on the stimulus and the cellular context. Elucidation of the underlying
      mechanisms might lead to novel therapeutic interventions.

PMID- 16990775
TI  - Correlation of neuropilin-1 overexpression to survival in acute myeloid leukemia.
AB  - Neuropilin-1 (NRP-1), a vascular endothelial growth factors and semaphorin
      receptor functioning as mediator of angiogenesis and neuronal guidance, is
      expressed by various solid tumors. The importance of NRP-1 in hematological
      malignancies such as acute myeloid leukemia (AML) remains to be elucidated.
      Therefore, we determined NRP-1 expression by immunohistochemical analysis of bone
      marrow biopsies of patients with newly diagnosed, untreated AML. The expression
      of NRP-1 was significantly increased in AML patients (n = 76; median 12.9
      arbitrary units (a.u.)) as compared with controls (n = 38; median 2.75 a.u.).
      Survival was significantly poorer in patients with high (> median) versus low (<
      or = median) NRP-1 expression levels with 5-year overall survival rates of 16.9
      versus 49.6% (P = 0.050). In conclusion, our data provide evidence of increased
      NRP-1 expression in AML with significant correlation to survival. Thus, NRP-1
      might constitute a promising target for antileukemic and antiangiogenic treatment
      strategies in AML.

PMID- 16990776
TI  - Infusion of bcr/abl peptide-reactive donor T cells to achieve molecular remission
      of chronic myeloid leukemia after CD34+ selected allogeneic hematopoietic cell
      transplantation.

PMID- 16990777
TI  - Elevated levels of serum CD44 and E-cadherin predict an unfavourable outcome in
      myelodysplastic syndromes.

PMID- 16990778
TI  - Alternative genetic pathways and cooperating genetic abnormalities in the
      pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia.
AB  - Alternative genetic pathways were previously outlined in the pathogenesis of
      therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML) based
      on cytogenetic characteristics. Some of the chromosome aberrations, the recurrent
      balanced translocations or inversions, directly result in chimeric rearrangement
      of genes for hematopoietic transcription factors (class II mutations) which
      disturb cellular differentiation. Other genetic abnormalities in t-MDS and t-AML
      comprise activating point mutations or internal tandem duplications of genes
      involved in signal transduction as tyrosine kinase receptors or genes more
      downstream in the RAS-BRAF pathway (class I mutations). The alternative genetic
      pathways of t-MDS and t-AML can now be further characterized by a different
      clustering of six individual class I mutations and mutations of AML1 and p53 in
      the various pathways. In addition, there is a significant association between
      class I and class II mutations possibly indicating cooperation in leukemogenesis,
      and between mutations of AML1 and RAS related to subsequent progression from t
      MDS to t-AML. Therapy-related and de novo myelodysplasia and acute myeloid
      leukemia seem to share genetic pathways, and surprisingly gene mutations were in
      general not more frequent in patients with t-MDS or t-AML as compared to similar
      cases of de novo MDS and AML studied previously.

PMID- 16990779
TI  - Improved human T-cell responses against synthetic HLA-0201 analog peptides
      derived from the WT1 oncoprotein.
AB  - Wilms tumor protein 1 (WT1) is a transcription factor overexpressed in several
      types of leukemia and solid tumors. For this reason, WT1 is an attractive target
      for immunotherapy. Four peptide nonamers from WT1 have been identified by others
      to generate a WT1-specific cytotoxic response in the context of human leukocyte
      antigen (HLA)-A0201 and A2402. However, as WT1 is a self-antigen, breaking
      tolerance is a potential obstacle to vaccination. Here, we use a strategy to
      circumvent tolerance by designing synthetic immunogenic analog peptides that
      could crossreact to the native peptides (a heteroclitic response). A number of
      synthetic peptides derived from nonamer sequences of the WT1 protein were
      designed in which single amino-acid substitutions were introduced at HLA-A0201
      major histocompatibility complex (MHC)-binding positions. Several of new peptides
      could stabilize MHC class I A0201 molecules better than native sequences. Some
      analogs were also able to elicit WT1-specific T-cell recognition and cytotoxic T
      cell lymphocytes more effectively than native sequences. Importantly, T cells
      stimulated with the new analogs crossreacted with the native WT1 peptide sequence
      and were able to kill HLA-matched chronic myeloid leukemia cell lines. In
      conclusion, analog heteroclitic WT1 peptides with increased immunogenicity can be
      synthesized and are potential cancer vaccine candidates.

PMID- 16990780
TI  - JAK2V617F mutational frequency in polycythemia vera: 100%, >90%, less?

PMID- 16990781
TI  - The familial risk of Hodgkin's lymphoma ranks among the highest in the Swedish
      Family-Cancer Database.

PMID- 16990782
TI  - Identification of a molecular signature for leukemic promyelocytes and their
      normal counterparts: Focus on DNA repair genes.
AB  - Acute promyelocytic leukemia (APL) is a clonal expansion of hematopoietic
      precursors blocked at the promyelocytic stage. Gene expression profiles of APL
      cells obtained from 16 patients were compared to eight samples of CD34+-derived
      normal promyelocytes. Malignant promyelocytes showed widespread changes in
      transcription in comparison to their normal counterpart and 1020 differentially
      expressed genes were identified. Discriminating genes include transcriptional
      regulators (FOS, JUN and HOX genes) and genes involved in cell cycle and DNA
      repair. The strong upregulation in APL of some transcripts (FLT3, CD33, CD44 and
      HGF) was also confirmed at protein level. Interestingly, a trend toward a
      transcriptional repression of genes involved in different DNA repair pathways was
      found in APL and confirmed by real-time polymerase chain reactor (PCR) in a new
      set of nine APLs. Our results suggest that both inefficient base excision repair
      and recombinational repair might play a role in APLs development. To investigate
      the expression pathways underlying the development of APL occurring as a second
      malignancy (sAPL), we included in our study eight cases of sAPL. Although both
      secondary and de novo APL were characterized by a strong homogeneity in
      expression profiling, we identified a small set of differentially expressed genes
      that discriminate sAPL from de novo cases.

PMID- 16990783
TI  - Alloreaction increases or restores CD40, CD54, and/or HLA molecule expression in
      acute myelogenous leukemia blasts, through secretion of inflammatory cytokines:
      Dominant role for TNFbeta, in concert with IFNgamma.
AB  - We have previously reported that alloreaction can lead to activation of dendritic
      cells through secretion of inflammatory cytokines. Here, we addressed whether
      alloreaction-derived cytokines may also lead to acute myelogenous leukemia (AML)
      blast differentiation. With this aim, supernatant (sn) harvested from major or
      minor histocompatibility antigen-mismatched mixed lymphocyte reaction (MLR) were
      used to culture French American Bristish (FAB) type M4 or M5 AML blasts. Our
      results showed that the secreted factors induced upregulation of CD40, CD54,
      and/or HLA molecules in AML blasts. Protein fractionation, blockade experiments
      and exogenous cytokine reconstitution demonstrated the involvement of TNF in the
      upregulation of CD54, CD40 and HLA-class II molecules, and of IFNgamma in the
      increase of HLA-class I and class II molecule expression. But, in line of its
      much higher levels of secretion, TNFbeta, rather than TNFalpha, was likely to
      play a preponderant role in AML blast differentiation. Moreover TNFbeta and
      IFNgamma were also likely to be involved in the AML blast differentiation
      mediated by HLA-identical donor T-cell alloresponse against recipient AML blasts.
      In conclusion, we show herein that upon allogeneic reaction, TNFbeta secretion
      contributes, in concert with IFNgamma, to increase or restore surface molecules
      involved in AML blast interaction with T cells.

PMID- 16990784
TI  - FLT3 K663Q is a novel AML-associated oncogenic kinase: Determination of
      biochemical properties and sensitivity to Sunitinib (SU11248).
AB  - Somatic mutations of FLT3 resulting in constitutive kinase activation are the
      most common acquired genomic abnormality found in acute myeloid leukemia (AML).
      The majority of these mutations are internal tandem duplications (ITD) of the
      juxtamembrane region (JM). In addition, a minority of cases of AML are associated
      with mutation of the FLT3 activation loop (AL), typically involving codons D835
      and/or I836. We hypothesized that other novel mutations of FLT3 could also
      contribute to leukemogenesis. We genotyped 109 cases of AML and identified two
      novel gain-of-function mutations. The first mutation, N841 H, is similar to
      previously described mutations involving amino-acid substitutions of codon 841.
      The other novel mutation, FLT3 K663Q, is the first AML-associated gain-of
      function mutation located outside the JM and AL domains. Of note, this mutation
      was potently inhibited by Sunitinib (SU11248), a previously described FLT3 kinase
      inhibitor. Sunitinib reduced the proliferation and induced apoptosis of
      transformed Ba/F3 cells expressing FLT3 K663Q. The potency of Sunitinib against
      FLT3 K663Q was similar to its potency against FLT3 ITD mutations. We conclude
      that FLT3 mutations in AML can involve novel regions of the TK1. Future studies
      are needed to define the incidence and prognostic significance of FLT3 mutations
      outside the well-established JM and AL regions.

PMID- 16990785
TI  - Identification of cryptic aberrations and characterization of translocation
      breakpoints using array CGH in high hyperdiploid childhood acute lymphoblastic
      leukemia.
AB  - High hyperdiploidy, characterized by non-random trisomies, is the largest
      cytogenetic subgroup in childhood acute lymphoblastic leukemia (ALL). It is not
      known whether the gained chromosomes are sufficient for leukemogenesis or if
      additional genetic aberrations are necessary. However, the suboptimal chromosome
      morphology of hyperdiploid ALLs makes detection of structural abnormalities
      difficult if using cytogenetic techniques; alternative methods are, therefore,
      needed. We performed array comparative genome hybridization (CGH) analyses, with
      a resolution of 100 kb, of eight cases of high hyperdiploid childhood ALL to
      characterize structural abnormalities found with G-banding/multicolor
      fluorescence in situ hybridization (FISH) and to detect novel changes. The non
      centromeric breakpoints of four rearrangements, including three translocations
      and one 1q duplication, were narrowed down to <0.2 Mb. Furthermore, four
      submicroscopic imbalances involving 0.6-2.7 Mb were detected, comprising two
      segmental duplications involving 1q22 and 12q24.31 in one case and two hemizygous
      deletions in 12p13.2-31 - including ETV6 - and in 13q32.3-33.1 in another case.
      Notably, FISH analysis of the latter revealed an associated reciprocal
      t(3;13)(q?;32.2-33.1). In conclusion, the array CGH analyses revealed putative
      leukemia-associated submicroscopic imbalances and rearrangements in 2/8 (25%)
      hyperdiploid ALLs. The detection and characterization of these additional genetic
      aberrations will most likely increase our understanding of the pathogenesis of
      high hyperdiploid childhood ALL.

PMID- 16990786
TI  - A dual-color FISH assay distinguishes between ELL and MLLT1 (ENL) gene
      rearrangements in t(11;19)-positive acute leukemia.

PMID- 16990787
TI  - Novel Ig V gene features of t(14;18) and t(3;14) de novo diffuse large B-cell
      lymphoma displaying germinal center-B cell like and non-germinal center-B cell
      like markers.

PMID- 16990788
TI  - The size of duplication does not add to the prognostic significance of FLT3
      internal tandem duplication in acute myeloid leukemia patients.

PMID- 16990789
TI  - Back to the future: education for systems-level biologists.
AB  - We describe a graduate course in quantitative biology that is based on original
      path-breaking papers in diverse areas of biology; each of these papers depends on
      quantitative reasoning and theory as well as experiment. Close reading and
      discussion of these papers allows students with backgrounds in physics,
      computational sciences or biology to learn essential ideas and to communicate in
      the languages of disciplines other than their own.

PMID- 16990790
TI  - Auxin in action: signalling, transport and the control of plant growth and
      development.
AB  - Hormones have been at the centre of plant physiology research for more than a
      century. Research into plant hormones (phytohormones) has at times been
      considered as a rather vague subject, but the systematic application of genetic
      and molecular techniques has led to key insights that have revitalized the field.
      In this review, we will focus on the plant hormone auxin and its action. We will
      highlight recent mutagenesis and molecular studies, which have delineated the
      pathways of auxin transport, perception and signal transduction, and which
      together define the roles of auxin in controlling growth and patterning.

PMID- 16990791
TI  - SPIN90/WISH interacts with PSD-95 and regulates dendritic spinogenesis via an N
      WASP-independent mechanism.
AB  - SPIN90/WISH (SH3 protein interacting with Nck, 90 kDa/Wiskott-Aldrich syndrome
      protein (WASP) interacting SH3 protein) regulates actin polymerization through
      its interaction with various actin-regulating proteins. It is highly expressed in
      the brain, but its role in the nervous system is largely unknown. We report that
      it is expressed in dendritic spines where it associates with PSD-95. Its
      overexpression increased the number and length of dendritic filopodia/spines via
      an N-WASP-independent mechanism, and knock down of its expression with small
      interfering RNA reduced dendritic spine density. The increase in spinogenesis is
      accompanied by an increase in synaptogenesis in contacting presynaptic neurons.
      Interestingly, PSD-95-induced dendritic spinogenesis was completely abolished by
      knock down of SPIN90/WISH. Finally, in response to chemically induced long-term
      potentiation, SPIN90/WISH associated with PSD-95 and was redistributed to
      dendritic spines. Our results suggest that SPIN90/WISH associates with PSD-95,
      and so becomes localized to dendritic spines where it modulates actin dynamics to
      control dendritic spinogenesis. They also raise the possibility that SPIN90/WISH
      is a downstream effector of PSD-95-dependent synaptic remodeling.

PMID- 16990792
TI  - Ordered assembly of Sld3, GINS and Cdc45 is distinctly regulated by DDK and CDK
      for activation of replication origins.
AB  - Initiation of chromosome DNA replication in eukaryotes is tightly regulated
      through assembly of replication factors at replication origins. Here, we
      investigated dependence of the assembly of the initiation complex on particular
      factors using temperature-sensitive fission yeast mutants. The psf3-1 mutant, a
      GINS component mutant, arrested with unreplicated DNA at the restrictive
      temperature and the DNA content gradually increased, suggesting a defect in DNA
      replication. The mutation impaired GINS complex formation, as shown by pull-down
      experiments. Chromatin immunoprecipitation assays indicated that GINS integrity
      was required for origin loading of Psf2, Cut5 and Cdc45, but not Sld3. In
      contrast, loading of Psf2 onto origins depended on Sld3 and Cut5 but not on
      Cdc45. These results suggest that Sld3 functions furthest upstream in initiation
      complex assembly, followed by GINS and Cut5, then Cdc45. Consistent with this
      conclusion, Cdc7-Dbf4 kinase (DDK) but not cyclin-dependent kinase (CDK) was
      required for Sld3 loading, whereas recruitment of the other factors depended on
      both kinases. These results suggest that DDK and CDK regulate distinct steps in
      activation of replication origins in fission yeast.

PMID- 16990793
TI  - PtdIns3P binding to the PX domain of p40phox is a physiological signal in NADPH
      oxidase activation.
AB  - The production of reactive oxygen species by the NADPH oxidase complex of
      phagocytes plays a critical role in our defence against bacterial and fungal
      infections. The PX domains of two oxidase components, p47(phox) and p40(phox),
      are known to bind phosphoinositide products of PI3Ks but the physiological roles
      of these interactions are unclear. We have created mice which carry an R58A
      mutation in the PX domain of their p40(phox) gene, which selectively prevents
      binding to PtdIns3P. p40(phoxR58A/R58A) embryos do not develop normally but
      p40(phoxR58A/-) mice are viable and neutrophils from these animals exhibit
      significantly reduced oxidase responses compared to those from their p40(phox+/-)
      siblings (e.g. 60% reduced in response to phagocytosis of Staphylococcus aureus).
      Wortmannin inhibition of the S. aureus oxidase response correlates with
      inhibition of phagosomal PtdIns3P accumulation and overlaps with the reduction in
      this response caused by the R58A mutation, suggesting PI3K regulation of this
      response is substantially dependent on PtdIns3P-binding to p40(phox).
      p40(phoxR58A/-) mice are significantly compromised in their ability to kill S.
      aureus in vivo, defining the physiological importance of this interaction.

PMID- 16990794
TI  - Two roles for Rad50 in telomere maintenance.
AB  - We describe two roles for the Rad50 protein in telomere maintenance and the
      protection of chromosome ends. Using fluorescence in situ hybridisation (FISH)
      and fibre-FISH analyses, we show that absence of AtRad50 protein leads to rapid
      shortening of a subpopulation of chromosome ends and subsequently chromosome-end
      fusions lacking telomeric repeats. In the absence of telomerase, mutation of
      atrad50 has a synergistic effect on the number of chromosome end fusions.
      Surprisingly, this 'deprotection' of the shortened telomeres does not result in
      increased exonucleolytic degradation, but in a higher proportion of anaphase
      bridges containing telomeric repeats in atrad50/tert plants, compared to tert
      mutant plants. Absence of AtRad50 thus facilitates the action of recombination on
      these shortened telomeres. We propose that this protective role of Rad50 protein
      on shortened telomeres results from its action in constraining recombination to
      sister chromatids and thus avoiding end-to-end interactions.

PMID- 16990795
TI  - Regulation of p53 tumour suppressor target gene expression by the p52 NF-kappaB
      subunit.
AB  - The p52/p100 nuclear factor kappa B (NF-kappaB) subunit (NF-kappaB2) is
      aberrantly expressed in many tumour types and has been implicated as a regulator
      of cell proliferation. Here, we demonstrate that endogenous p52 is a direct
      regulator of Cyclin D1 expression. However, stimulation of Cyclin D1 expression
      alone cannot account for all the cell cycle effects of p52/p100 and we also find
      that p52 represses expression of the Cyclin-dependent kinase inhibitor
      p21(WAF/CIP1). Significantly, this latter effect is dependent upon basal levels
      of the tumour suppressor p53. By contrast, p52 cooperates with p53 to regulate
      other known p53 target genes such as PUMA, DR5, Gadd45alpha and Chk1. p52
      associates directly with these p53-regulated promoters where it regulates
      coactivator and corepressor binding. Moreover, recruitment of p52 is p53
      dependent and does not require p52-DNA-binding activity. These results reveal a
      complex role for p52 as regulator of cell proliferation and p53 transcriptional
      activity. Furthermore, they imply that in some cell types, p52 can regulate p53
      function and influence p53-regulated decision-making following DNA damage and
      oncogene activation.

PMID- 16990796
TI  - PSD-95 is a negative regulator of the tyrosine kinase Src in the NMDA receptor
      complex.
AB  - The tyrosine kinase Src upregulates the activity of the N-methyl-D-aspartate
      subtype of glutamate receptor (NMDAR) and tyrosine phosphorylation of this
      receptor is critical for induction of NMDAR-dependent plasticity of synaptic
      transmission. A binding partner for Src within the NMDAR complex is the protein
      PSD-95. Here we demonstrate an interaction of PSD-95 with Src that does not
      require the well-characterized domains of PSD-95. Rather, we show binding to Src
      through a 12-amino-acid sequence in the N-terminal region of PSD-95, a region not
      previously known to participate in protein-protein interactions. This region
      interacts directly with the Src SH2 domain. Contrary to typical SH2 domain
      binding, the PSD-95-Src SH2 domain interaction is phosphotyrosine-independent.
      Binding of the Src-interacting region of PSD-95 inhibits Src kinase activity and
      reduces NMDAR phosphorylation. Intracellularly administering a peptide matching
      the Src SH2 domain-interacting region of PSD-95 depresses NMDAR currents in
      cultured neurons and inhibits induction of long-term potentiation in hippocampus.
      Thus, the PSD-95-Src SH2 domain interaction suppresses Src-mediated NMDAR
      upregulation, a finding that may be of broad importance for synaptic transmission
      and plasticity.

PMID- 16990797
TI  - The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl
      leukotrienes receptor.
AB  - Nucleotides and cysteinyl-leukotrienes (CysLTs) are unrelated signaling molecules
      inducing multiple effects through separate G-protein-coupled receptors: the P2Y
      and the CysLT receptors. Here we show that GPR17, a Gi-coupled orphan receptor at
      intermediate phylogenetic position between P2Y and CysLT receptors, is
      specifically activated by both families of endogenous ligands, leading to both
      adenylyl cyclase inhibition and intracellular calcium increases. Agonist-response
      profile, as determined by [(35)S]GTPgammaS binding, was different from that of
      already known CysLT and P2Y receptors, with EC(50) values in the nanomolar and
      micromolar range, for CysLTs and uracil nucleotides, respectively. Both rat and
      human receptors are highly expressed in the organs typically undergoing ischemic
      damage, that is, brain, heart and kidney. In vivo inhibition of GPR17 by either
      CysLT/P2Y receptor antagonists or antisense technology dramatically reduced
      ischemic damage in a rat focal ischemia model, suggesting GPR17 as the common
      molecular target mediating brain damage by nucleotides and CysLTs. In conclusion,
      the deorphanization of GPR17 revealed a dualistic receptor for two endogenous
      unrelated ligand families. These findings may lead to dualistic drugs of
      previously unexplored therapeutic potential.

PMID- 16990799
TI  - An eIF5/eIF2 complex antagonizes guanine nucleotide exchange by eIF2B during
      translation initiation.
AB  - In eukaryotic translation initiation, the eIF2.GTP/Met-tRNA(i)(Met) ternary
      complex (TC) binds the eIF3/eIF1/eIF5 complex to form the multifactor complex
      (MFC), whereas eIF2.GDP binds the pentameric factor eIF2B for guanine nucleotide
      exchange. eIF5 and the eIF2Bvarepsilon catalytic subunit possess a conserved eIF2
      binding site. Nearly half of cellular eIF2 forms a complex with eIF5 lacking Met
      tRNA(i)(Met), and here we investigate its physiological significance. eIF5
      overexpression increases the abundance of both eIF2/eIF5 and TC/eIF5 complexes,
      thereby impeding eIF2B reaction and MFC formation, respectively. eIF2Bvarepsilon
      mutations, but not other eIF2B mutations, enhance the ability of overexpressed
      eIF5 to compete for eIF2, indicating that interaction of eIF2Bvarepsilon with
      eIF2 normally disrupts eIF2/eIF5 interaction. Overexpression of the catalytic
      eIF2Bvarepsilon segment similarly exacerbates eIF5 mutant phenotypes, supporting
      the ability of eIF2Bvarepsilon to compete with MFC. Moreover, we show that eIF5
      overexpression does not generate aberrant MFC lacking tRNA(i)(Met), suggesting
      that tRNA(i)(Met) is a vital component promoting MFC assembly. We propose that
      the eIF2/eIF5 complex represents a cytoplasmic reservoir for eIF2 that
      antagonizes eIF2B-promoted guanine nucleotide exchange, enabling coordinated
      regulation of translation initiation.

PMID- 16990798
TI  - Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia
      associated MLL histone methyltransferase.
AB  - Methylation of CpG dinucleotides is the major epigenetic modification of
      mammalian genomes, critical for regulating chromatin structure and gene activity.
      The mixed-lineage leukaemia (MLL) CXXC domain selectively binds nonmethyl-CpG
      DNA, and is required for transformation by MLL fusion proteins that commonly
      arise from recurrent chromosomal translocations in infant and secondary treatment
      related acute leukaemias. To elucidate the molecular basis of nonmethyl-CpG DNA
      recognition, we determined the structure of the human MLL CXXC domain by
      multidimensional NMR spectroscopy. The CXXC domain has a novel fold in which two
      zinc ions are each coordinated tetrahedrally by four conserved cysteine ligands
      provided by two CGXCXXC motifs and two distal cysteine residues. We have
      identified the CXXC domain DNA binding interface by means of chemical shift
      perturbation analysis, cross-saturation transfer and site-directed mutagenesis.
      In particular, we have shown that residues in an extended surface loop are in
      close contact with the DNA. These data provide a template for the design of
      specifically targeted therapeutics for poor prognosis MLL-associated leukaemias.

PMID- 16990800
TI  - A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37
      to 26S proteasomes.
AB  - The 26S proteasome is a multisubunit protease responsible for regulated
      proteolysis in eukaryotic cells. It is composed of one catalytic 20S proteasome
      and two 19S regulatory particles attached on both ends of 20S proteasomes. Here,
      we describe the identification of Adrm1 as a novel proteasome interacting protein
      in mammalian cells. Although the overall sequence of Adrm1 has weak homology with
      the yeast Rpn13, the amino- and carboxyl-terminal regions exhibit significant
      homology. Therefore, we designated it as hRpn13. hRpn13 interacts with a base
      subunit Rpn2 via its amino-terminus. The majority of 26S proteasomes contain
      hRpn13, but a portion of them does not, indicating that hRpn13 is not an integral
      subunit. Intriguingly, we found that hRpn13 recruits UCH37, a deubiquitinating
      enzyme known to associate with 26 proteasomes. The carboxyl-terminal regions
      containing KEKE motifs of both hRpn13 and UCH37 are involved in their physical
      interaction. Knockdown of hRpn13 caused no obvious proteolytic defect but loss of
      UCH37 proteins and decrease in deubiquitinating activity of 26S proteasomes. Our
      results indicate that hRpn13 is essential for the activity of UCH37.

PMID- 16990801
TI  - Smads orchestrate specific histone modifications and chromatin remodeling to
      activate transcription.
AB  - Smads are intracellular transducers for TGF-beta superfamily ligands, but little
      is known about the mechanism by which complexes of receptor-phosphorylated Smad2
      and Smad4 regulate transcription. Using an in vitro transcription system, we have
      discovered that, unlike most transcription factors that are sufficient to recruit
      the basal transcription machinery and therefore activate transcription on both
      naked DNA and chromatin templates, the Smads only activate transcription from
      chromatin templates. We demonstrate that Smad2-mediated transcription requires
      the histone acetyltransferase, p300. Smad2-recruited p300 exhibits an altered
      substrate specificity, specifically acetylating nucleosomal histone H3 at lysines
      9 and 18, and these modifications are also detected on an endogenous Smad2
      dependent promoter in a ligand-induced manner. Furthermore, we show that
      endogenous Smad2 interacts with the SWI/SNF ATPase, Brg1, in a TGF-beta-dependent
      manner, and demonstrate that Brg1 is recruited to Smad2-dependent promoters and
      is specifically required for TGF-beta-induced expression of endogenous Smad2
      target genes. Our data indicate that the Smads define a new class of
      transcription factors that absolutely require chromatin to assemble the basal
      transcription machinery and activate transcription.

PMID- 16990802
TI  - Null mutations in the filaggrin gene (FLG) determine major susceptibility to
      early-onset atopic dermatitis that persists into adulthood.
AB  - Atopic dermatitis (AD) is a common disease with a complex etiology in childhood
      and adult life. A significant proportion of childhood AD is transient, but in
      many cases it persists into adulthood. We have recently shown that null mutations
      in the filaggrin gene (FLG) are an important predisposing factor for childhood
      eczema and eczema-associated asthma, but persistence to adulthood has not been
      analyzed. Here we studied a cohort of adult patients with persistent AD, which
      had been present since early childhood. In this cohort, the combined allele
      frequency of the two common FLG null variants was 0.270 (cf. population frequency
      0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3
      10.9 and a chi2 P-value of 1.7 x 10(-53). Our data conclusively demonstrate that
      identification of FLG null alleles is an indicator of a poor prognosis in AD,
      predisposing to a form of eczema that starts in early infancy and persists into
      adulthood. This study helps to further define the nature of the AD phenotype
      associated with FLG null alleles.

PMID- 16990803
TI  - Xeroderma pigmentosum group C in an isolated region of Guatemala.

PMID- 16990804
TI  - Generalized epidermolytic hyperkeratosis in two unrelated children from parents
      with localized linear form, and prenatal diagnosis.

PMID- 16990805
TI  - Genetic variants of the vitamin D receptor gene alter risk of cutaneous melanoma.
AB  - Sunlight causes DNA damage but also induces production of vitamin D whose
      metabolite 1,25-(OH)2D3 has antiproliferative and pro-differentiative effects in
      both melanocytes and cutaneous melanoma (CM) cells mediated through the vitamin D
      receptor (VDR). We hypothesized that genetic polymorphisms of VDR are associated
      with risk of CM. In a hospital-based case-control study of 602 non-Hispanic white
      CM patients and 603 cancer-free control subjects frequency matched by age and
      sex, we genotyped two VDR polymorphisms (TaqI and FokI) and assessed their
      association with CM risk. We found that a significantly decreased risk was
      associated with VDR-TaqI Tt (adjusted odds ratio (OR), 0.70; 95% confidence
      interval (CI), 0.54-0.90) and Tt+tt (OR=0.70; 95% CI, 0.55-0.89) genotypes,
      compared with the VDR-TaqI TT genotype, whereas an increased risk was associated
      with VDR-FokI Ff genotype (OR=1.32; 95% CI, 1.03-1.68), and a borderline
      significantly increased risk was associated with Ff+ff (OR=1.26; 95% CI, 1.00
      1.59) genotypes, compared with the VDR-FokI FF genotype. In conclusion, genetic
      variants (i.e., TaqI t protective allele and FokI f risk allele) in VDR may alter
      risk of CM.

PMID- 16990806
TI  - Measuring cognitive deficits in disabled mice using an automated interactive
      touchscreen system.

PMID- 16990807
TI  - Minimizing the risk of reporting false positives in large-scale RNAi screens.
AB  - Large-scale RNA interference (RNAi)-based analyses, very much as other 'omic'
      approaches, have inherent rates of false positives and negatives. The variability
      in the standards of care applied to validate results from these studies, if left
      unchecked, could eventually begin to undermine the credibility of RNAi as a
      powerful functional approach. This Commentary is an invitation to an open
      discussion started among various users of RNAi to set forth accepted standards
      that would insure the quality and accuracy of information in the large datasets
      coming out of genome-scale screens.

PMID- 16990808
TI  - Single-molecule mountains yield nanoscale cell images.

PMID- 16990809
TI  - The inside track on HIV.

PMID- 16990810
TI  - Channelrhodopsin-2 and optical control of excitable cells.
AB  - Electrically excitable cells are important in the normal functioning and in the
      pathophysiology of many biological processes. These cells are typically embedded
      in dense, heterogeneous tissues, rendering them difficult to target selectively
      with conventional electrical stimulation methods. The algal protein
      Channelrhodopsin-2 offers a new and promising solution by permitting minimally
      invasive, genetically targeted and temporally precise photostimulation. Here we
      explore technological issues relevant to the temporal precision, spatial
      targeting and physiological implementation of ChR2, in the context of other
      photostimulation approaches to optical control of excitable cells.

PMID- 16990811
TI  - Imaging diacylglycerol dynamics at organelle membranes.
AB  - Fluorescence imaging is a powerful technique to visualize spatiotemporal dynamics
      of biomolecules in living cells. We describe fluorescent indicators for a lipid
      second messenger, diacylglycerol (DAG), which allow the localized analysis of DAG
      dynamics at subcellular membranes. We have thus pinpointed that DAG
      concentrations increase and/or decrease at not only the plasma membrane but also
      organelle membranes such as endomembranes and mitochondrial outer membranes.

PMID- 16990812
TI  - Defining the actual sensitivity and specificity of the neurosphere assay in stem
      cell biology.
AB  - For more than a decade the 'neurosphere assay' has been used to define and
      measure neural stem cell (NSC) behavior, with similar assays now used in other
      organ systems and in cancer. We asked whether neurospheres are clonal structures
      whose diameter, number and composition accurately reflect the proliferation, self
      renewal and multipotency of a single founding NSC. Using time-lapse video
      microscopy, coculture experiments with genetically labeled cells, and analysis of
      the volume of spheres, we observed that neurospheres are highly motile structures
      prone to fuse even under ostensibly 'clonal' culture conditions. Chimeric
      neurospheres were prevalent independent of ages, species and neural structures.
      Thus, the intrinsic dynamic of neurospheres, as conventionally assayed,
      introduces confounders. More accurate conditions (for example, plating a single
      cell per miniwell) will be crucial for assessing clonality, number and fate of
      stem cells. These cautions probably have implications for the use of
      'cytospheres' as an assay in other organ systems and with other cell types, both
      normal and neoplastic.

PMID- 16990813
TI  - Clonal isolation of hESCs reveals heterogeneity within the pluripotent stem cell
      compartment.
AB  - Human embryonic stem cell (hESC) lines are known to be morphologically and
      phenotypically heterogeneous. The functional nature and relationship of cells
      residing within hESC cultures, however, has not been evaluated because isolation
      of single hESCs is limited to drug or manual selection. Here we provide a
      quantitative method using flow cytometry to isolate and clonally expand hESCs
      based on undifferentiated markers, alone or in combination with a fluorescent
      reporter. This method allowed for isolation of stage-specific embryonic antigen-3
      positive (SSEA-3+) and SSEA-3- cells from hESC cultures. Although both SSEA-3+
      and SSEA-3- cells could initiate pluripotent hESC cultures, we show that they
      possess distinct cell-cycle properties, clonogenic capacity and expression of ESC
      transcription factors. Our study provides formal evidence for heterogeneity among
      self-renewing pluripotent hESCs, illustrating that this isolation technique will
      be instrumental in further dissecting the biology of hESC lines.

PMID- 16990814
TI  - Quantitative four-dimensional tracking of cytoplasmic and nuclear HIV-1
      complexes.
AB  - Emerging real-time techniques for imaging viral infections provide powerful tools
      for understanding the dynamics of virus-host cell interactions. Here we labeled
      human immunodeficiency virus-1 (HIV-1) integrase with a small tetracysteine tag,
      which preserved the virus' infectivity while allowing it to be labeled with the
      bis-arsenical fluorescein derivative FlAsH. This labeling allowed us to image
      both intracytoplasmic and intranuclear HIV-1 complexes in three dimensions over
      time (4D) in human cells and enabled us to analyze HIV-1 kinetics by automated 4D
      quantitative particle tracking. In the cytoplasm, HIV-1 complexes underwent
      directed movements toward the nuclear compartment, kinetically characteristic of
      both microtubule- and actin-dependent transport. The complexes then adopted
      smaller movements in a very confined volume once associated with the nuclear
      membrane and more diffuse movements once inside the nucleus. This work
      contributes new insight into the various movements of HIV-1 complexes within
      infected cells and provides a useful tool for the study of virus-host cell
      interactions during infection.

PMID- 16990815
TI  - State-based discovery: a multidimensional screen for small-molecule modulators of
      EGF signaling.
AB  - As an alternative to conventional, target-oriented drug discovery, we report a
      strategy that identifies compounds on the basis of the state that they induce in
      a signaling network. Immortalized human cells are grown in microtiter plates and
      treated with compounds from a small-molecule library. The target network is then
      activated and lysates derived from each sample are arrayed onto glass-supported
      nitrocellulose pads. By probing these microarrays with antibodies that report on
      the abundance or phosphorylation state of selected proteins, a global picture of
      the target network is obtained. As proof of concept, we screened 84 kinase and
      phosphatase inhibitors for their ability to induce different states in the ErbB
      signaling network. We observed functional connections between proteins that match
      our understanding of ErbB signaling, indicating that state-based screens can be
      used to define the topology of signaling networks. Additionally, compounds sort
      according to the multidimensional phenotypes they induce, suggesting that state
      based screens may inform efforts to identify the targets of biologically active
      small molecules.

PMID- 16990816
TI  - A recombineering pipeline for functional genomics applied to Caenorhabditis
      elegans.
AB  - We present a new concept in DNA engineering based on a pipeline of serial
      recombineering steps in liquid culture. This approach is fast, straightforward
      and facilitates simultaneous processing of multiple samples in parallel. We
      validated the approach by generating green fluorescent protein (GFP)-tagged
      transgenes from Caenorhabditis briggsae genomic clones in a multistep pipeline
      that takes only 4 d. The transgenes were engineered with minimal disturbance to
      the natural genomic context so that the correct level and pattern of expression
      will be secured after transgenesis. An example transgene for the C. briggsae
      ortholog of lin-59 was used for ballistic transformation in Caenorhabditis
      elegans. We show that the cross-species transgene is correctly expressed and
      rescues RNA interference (RNAi)-mediated knockdown of the endogenous C. elegans
      gene. The strategy that we describe adapts the power of recombineering in
      Escherichia coli for fluent DNA engineering to a format that can be directly
      scaled up for genomic projects.

PMID- 16990817
TI  - In vivo and in vitro protein solubility assays using split GFP.
AB  - The rapid assessment of protein solubility is essential for evaluating expressed
      proteins and protein variants for use as reagents for downstream studies.
      Solubility screens based on antibody blots are complex and have limited screening
      capacity. Protein solubility screens using split beta-galactosidase in vivo and
      in vitro can perturb protein folding. Split GFP used for monitoring protein
      interactions folds poorly, and to overcome this limitation, we recently developed
      a protein-tagging system based on self-complementing split GFP derived from an
      exceptionally well folded variant of GFP termed 'superfolder GFP'. Here we
      present the step-by-step procedure of the solubility assay using split GFP. A 15
      amino-acid GFP fragment, GFP 11, is fused to a test protein. The GFP 1-10
      detector fragment is expressed separately. These fragments associate
      spontaneously to form fluorescent GFP. The fragments are soluble, and the GFP 11
      tag has minimal effect on protein solubility and folding. We describe high
      throughput protein solubility screens amenable both for in vivo and in vitro
      formats. The split-GFP system is composed of two vectors used in the same strain:
      pTET GFP 11 and pET GFP 1-10 (Fig. 1 and Supplementary Note online). The gene
      encoding the protein of interest is cloned into the pTET GFP 11 vector (resulting
      in an N-terminal fusion) and transformed into Escherichia coli BL21 (DE3) cells
      containing the pET GFP 1-10 plasmid. We also describe how this system can be used
      for selecting soluble proteins from a library of variants (Box 1). The large
      screening power of the in vivo assay combined with the high accuracy of the in
      vitro assay point to the efficiency of this two-step split-GFP tool for
      identifying soluble clones suitable for purification and downstream applications.

PMID- 16990819
TI  - Teaching and learning empathy.

PMID- 16990820
TI  - Levodopa--toxic or neuroprotective?

PMID- 16990821
TI  - How effective is intensive migraine education provided by migraineurs?

PMID- 16990822
TI  - How effective is citalopram in actual practice?

PMID- 16990823
TI  - Can lumbar puncture help to identify patients with incipient Alzheimer's disease?

PMID- 16990824
TI  - Should all patients at high risk of atherothrombotic events receive dual
      antiplatelet therapy?

PMID- 16990825
TI  - Do neurologists provide adequate care for depression in patients with multiple
      sclerosis?

PMID- 16990826
TI  - Is tetrabenazine safe and effective for suppressing chorea in Huntington's
      disease?

PMID- 16990827
TI  - Vascular cognitive impairment.
AB  - Cognitive impairment commonly accompanies clinical syndromes associated with
      vascular disease of the brain. Because of evolving definitional criteria,
      however, the frequency of cognitive impairment attributable to cerebrovascular
      disease is difficult to determine. Dementia occurs in up to one-third of elderly
      patients with stroke, a subset of whom have Alzheimer's disease (AD) rather than
      a pure vascular dementia syndrome. In fact, pure vascular dementia has been shown
      to be uncommon in most large autopsy series. A mixed etiology of AD and
      cerebrovascular disease is thought to become more common with increasing age,
      although no clinical criteria for the diagnosis of AD with cerebrovascular
      disease are currently available. Epidemiological studies have implicated
      subcortical small-vessel disease as a risk factor for cognitive impairment and
      dementia, but the cognitive expression and clinical significance of MRI white
      matter changes in individual patients is difficult to establish. The frequency of
      specific neuropathologic features of vascular cognitive impairment depends
      largely on study inclusion criteria. Cerebral meningocortical microangiopathies
      with distinctive clinicopathological profiles are associated with dementia in
      both sporadic cases and familial syndromes. In patients with AD, the contribution
      of amyloid-beta protein to the degree of cognitive impairment has not been
      clearly defined.

PMID- 16990828
TI  - Narcolepsy and the hypocretin system--where motion meets emotion.
AB  - Narcolepsy is a neurological disorder that is characterized by excessive daytime
      sleepiness and cataplexy--a loss of muscle tone generally triggered by certain
      strong emotions with sudden onset. The underlying cause of most cases of human
      narcolepsy is a loss of neurons that produce hypocretin (Hcrt, also known as
      orexin). These cells normally serve to drive and synchronize the activity of
      monoaminergic and cholinergic cells. Sleepiness results from the reduced activity
      of monoaminergic, cholinergic and other cells that are normally activated by Hcrt
      neurons, as well as from the loss of Hcrt itself. Cataplexy is caused by an
      episodic loss of activity in noradrenergic cells that support muscle tone, and a
      linked activation of a medial medullary cell population that suppresses muscle
      tone. Current treatments for narcolepsy include stimulants to combat sleepiness
      and antidepressants to reduce cataplexy. Sodium oxybate produces both reductions
      in cataplexy and improved waking alertness. Future treatments are likely to
      include Hcrt or Hcrt agonists to reverse the underlying neurochemical deficit.

PMID- 16990829
TI  - Therapy Insight: CNS manifestations of HIV-associated immune reconstitution
      inflammatory syndrome.
AB  - The introduction of combination antiretroviral therapy for HIV infection has
      prolonged the lives of patients with AIDS. It is increasingly being recognized,
      however, that following initiation of this therapy some patients can develop a
      paradoxical neurological deterioration, despite dramatic improvements in HIV
      viral load and CD4+ T-cell counts. This immune reconstitution inflammatory
      syndrome (IRIS) in the CNS is emerging as an important neurological complication,
      particularly as antiretroviral therapy is now becoming readily available
      worldwide. Currently, there are no guidelines for prevention, diagnosis or
      treatment of the CNS manifestations of IRIS. Even in patients with an acute
      presentation, the diagnosis can be challenging. Furthermore, it is possible that
      more-chronic forms of the syndrome exist but remain unrecognized. Here, we review
      the various clinical presentations of CNS IRIS, and discuss options for their
      management.

PMID- 16990831
TI  - Fostering empathy in neurology training.

PMID- 16990830
TI  - Anti-Ma2-associated encephalitis with normal FDG-PET: a case of pseudo-Whipple's
      disease.
AB  - BACKGROUND: A 39-year-old man presented with a history of several months of
      progressive personality changes, social withdrawal, bradykinesia, mutism,
      dysphagia, worsening gait, and difficulty with daily living activities.
      Examination revealed an atypical parkinsonian appearance with incomplete
      supranuclear ophthalmoplegia and an unusual oculomotor disorder characterized by
      both low-amplitude, intermittent opsoclonus, and slow, nystagmoid intrusions.
      INVESTIGATIONS: Routine laboratory testing, autoimmune and infectious serologies,
      brain MRI, lumbar puncture, electroencephalogram, whole-body CT scan,
      paraneoplastic serologies, small bowel biopsy, 18F-fluorodeoxyglucose positron
      emission tomography CT scan, brain biopsy, and testicular ultrasound. DIAGNOSIS:
      Anti-Ma2 paraneoplastic encephalitis in association with metastatic testicular
      cancer; initially misdiagnosed as CNS Whipple's disease. MANAGEMENT:
      Corticosteroids, intravenous immunoglobulins, orchiectomy, muscle relaxants,
      mycophenolate mofetil, plasmapheresis, and bleomycin, etoposide and platinum
      chemotherapy.

PMID- 16990832
TI  - Acute cerebrovascular syndrome: time for new terminology for acute brain
      ischemia.

PMID- 16990833
TI  - Identification of women with heart disease: a missed opportunity.

PMID- 16990834
TI  - Does clopidogrel pretreatment counteract the benefits of off-pump CABG surgery?

PMID- 16990835
TI  - Is elevated cardiovascular risk a class effect of cyclo-oxygenase 2 inhibitors?

PMID- 16990836
TI  - Can 32-detector-row CT exclude significant stenoses in coronary artery disease
      patients with high calcium scores?

PMID- 16990837
TI  - Is sitaxsentan a safe and efficacious treatment for pulmonary arterial
      hypertension?

PMID- 16990838
TI  - Laparoscopy-assisted abdominal aortic aneurysm repair: a future standard of care?

PMID- 16990839
TI  - Apolipoprotein A-I mimetic peptides and their role in atherosclerosis prevention.
AB  - The importance of apolipoprotein A-I (apoA-I) in atherosclerosis was established
      by testing in animal models, and its potential usefulness in humans has been
      confirmed in preliminary studies. ApoA-I is a large protein comprising 243 amino
      acids, which means that venous administration is necessary. In addition,
      manufacture of apoA-I is difficult and expensive. Research has, therefore, been
      directed towards finding smaller peptide mimetics that produce similar results to
      apoA-I, but that are easier to manufacture and administer. The earliest peptides
      mimicked some of the lipid-binding properties of apoA-I but did not prevent
      atherosclerosis in mice. A detailed study of the physical-chemical
      characteristics of these peptides led to the realization that the hydrophobic
      region of the peptide was critical in determining bioactivity. A potent peptide,
      4F, which was synthesized wholly from D-amino acids, could be given orally. Use
      of 4F significantly improved the function of HDL in mice and monkeys. When 4F was
      administered in combination with a statin, lesion size and macrophage content
      were reduced in mice with atherosclerosis, and lesions regressed in older mice.
      Vasoreactivity and endothelial sloughing were also improved in other rodent
      studies. Early human clinical trials are now being carried out on 4F. Here, we
      review the studies on apoA-I mimetic peptides that have been carried out so far.

PMID- 16990840
TI  - Therapy insight: malignant primary cardiac tumors.
AB  - Benign cardiac tumors are resected with a high degree of success with modern
      cardiac surgical techniques. Malignant cardiac tumors, however, continue to pose
      a therapeutic challenge to cardiac surgeons and oncologists because of the
      technical difficulty involved in extensive cardiac resections and the aggressive
      biological nature of the tumors. The majority of malignant cardiac tumors are
      sarcomas and can be categorized as right heart sarcoma, left heart sarcoma or
      pulmonary artery sarcoma. Right heart sarcomas are generally angiosarcomas, which
      infiltrate widely and metastasize early. A combination of chemotherapy and
      surgical resection is the preferred therapy. Left heart sarcomas, although large,
      are often less infiltrative and metastasize later than right heart sarcomas, but
      a similar approach to treatment is usually employed. Surgical resection is more
      frequently necessary for left heart sarcomas because of intracardiac blood flow
      obstruction and congestive heart failure, although the anatomic position and
      relation of these tumors to cardiac structures can complicate surgery. We have
      developed and employed the technique of cardiac autotransplantation, which
      involves cardiac excision, ex vivo tumor resection with cardiac reconstruction,
      and cardiac reimplantation, to lessen these technical difficulties. Pulmonary
      artery sarcomas can be treated by radiotherapy, as well as by the other
      therapies, because the myocardium can be avoided by the radiation fields.
      Surgical resection of this sarcoma type often requires pneumonectomy and can
      require pulmonary root replacement.

PMID- 16990841
TI  - Technology insight: in vivo cell tracking by use of MRI.
AB  - Animal studies have shown some success in the use of stem cells of diverse
      origins to treat heart failure and ventricular dysfunction secondary to ischemic
      injury. The clinical use of these cells is, therefore, promising. In order to
      develop effective cell therapies, the location, distribution and long-term
      viability of these cells must be evaluated in a noninvasive manner. MRI of cells
      labeled with magnetically visible contrast agents after either direct injection
      or local or intravenous infusion has the potential to fulfill this goal. In this
      Review, techniques for labeling and imaging a variety of cells will be discussed.
      Particular attention will be given to the advantages and limitations of various
      contrast agents and passive and facilitated cell-labeling methods, as well as to
      imaging techniques that produce negative and positive contrast, and the effect on
      image quantification of compartmentalization of contrast agents within the cell.

PMID- 16990842
TI  - Mechanisms of disease: erythropoietin--an old hormone with a new mission?
AB  - The major physiological function of erythropoietin is the induction of
      erythropoiesis. A growing body of evidence indicates, however, that this hormone
      has tissue-protective effects and prevents tissue damage during ischemia and
      inflammation. This review article summarizes the present knowledge on the
      cardiovascular and renal protective effects of erythropoietin and discusses the
      possible underlying mechanisms.

PMID- 16990843
TI  - Recurrent syncope: an unusual presentation of Brugada syndrome.
AB  - BACKGROUND: A 55-year-old man presented at hospital with recurrent syncope. He
      did not have any prodromic symptoms and did not report having palpitations,
      dizziness or chest pain before, during or after the syncopal episodes. He had no
      family history of either syncope or sudden cardiac death. The patient was
      initially diagnosed with carotid sinus hypersensitivity and received a dual
      chamber, rate-modulated pacemaker. Several months later, he presented at hospital
      again having had two more syncopal episodes. INVESTIGATIONS: Physical
      examination, electrocardiography, echocardiography, cerebral CT scan, and carotid
      sinus massage. DIAGNOSIS: Syncope associated with Brugada syndrome. MANAGEMENT:
      Implantation of a cardioverter-defibrillator.

PMID- 16990844
TI  - Gene therapy of liver tumors with human liver-specific nanoparticles.
AB  - The development of safe and efficient liver-specific gene delivery approaches
      offers new perspectives for the treatment of liver disease, in particular, liver
      cancer. We evaluated the therapeutic potential of hepatotropic nanoparticles for
      gene therapy of liver tumor. These nanoparticles do not contain a viral genome
      and display the hepatitis B virus L antigen, which is essential to confer hepatic
      specificity. It has not been shown whether a therapeutic effect could be obtained
      using L nanoparticles in a human liver tumor xenograft model. Rats bearing human
      hepatic (NuE) and non-hepatic tumors were injected with L nanoparticles
      containing a green fluorescent protein (GFP) expression plasmid. GFP expression
      was observed only in NuE-derived tumors but not in the non-hepatic tumor. The
      potential for treatment of liver tumors was analyzed using L nanoparticles
      containing the herpes simplex virus thymidine kinase gene, in conjunction with
      ganciclovir pro-drug administration. The growth of NuE-derived tumors in L
      particle-injected rats was significantly suppressed, but not of the non-hepatic
      tumor control. In summary, this is the first demonstration that nanoparticles
      could be used for delivery of therapeutic genes with anti-tumor activity into
      human liver tumors. This intravenous delivery system may be one of the major
      advantages as compared to many other viral vector systems.

PMID- 16990845
TI  - Replication-deficient rSV40 mediate pancreatic gene transfer and long-term
      inhibition of tumor growth.
AB  - Pancreatic cancer is one of the most aggressive and devastating human
      malignancies. There is an urgent need for more effective therapy for patients
      with advanced disease. In this context, genetic therapy potentially represents a
      rational new approach to treating pancreatic cancer, which could provide an
      adjunct to conventional options. Because of the promise of recombinant SV40
      vectors, we tested their ability to deliver a transgene, and to target a
      transcript, so as to inhibit pancreatic tumors growth in vivo. BxPC3 and Capan-1
      cells were efficiently transduced using SV40 vectors without selection, as
      compared to synthetic vectors PEI. SV40 vectors were as efficient as adenoviral
      vectors, and provided long-term transgene expression. Next, we devised a SV40
      derived, targeted gene therapy approach of pancreatic cancer, by combining hTR
      tumor-specific promoter with sst2 somatostatin receptor tumor-suppressor gene. In
      vitro cell proliferation was strongly impaired following administration of SV(hTR
      sst2). SV40-derived sst2-mediated antiproliferative effect was dependent on the
      local production of somatostatin. In vivo, intratumoral gene transfer of sst2
      using rSV40 vectors resulted in a marked inhibition of Capan-1 tumor progression,
      and proliferation. These results represent the initial steps toward a novel
      approach to the gene therapy of pancreatic cancer using SV40 as a vector.

PMID- 16990846
TI  - Engineered herpes simplex virus expressing bacterial cytosine deaminase for
      experimental therapy of brain tumors.
AB  - Lack of effective therapy of primary brain tumors has promoted the development of
      novel experimental approaches utilizing oncolytic viruses combined with gene
      therapy. Towards this end, we have assessed a conditionally replication
      competent, gamma(1)34.5-deleted herpes simplex virus type 1 (HSV-1) expressing
      cytosine deaminase (CD) for treatment of malignant brain tumors. Our results are
      summarized as follows: (i) a recombinant HSV (M012) was constructed in which both
      copies of the gamma(1)34.5 gene were replaced with the bacterial CD gene, under
      the control of the cellular promoter Egr-1; (ii) M012-infected cells in vitro
      efficiently convert 5-fluorocytosine (5-FC) to 5-fluorouracil, thereby enhancing
      cytotoxicity of neighboring, uninfected cells; (iii) both direct and bystander
      cytotoxicity of murine neuroblastoma and human glioma cell lines after infection
      with M012 were demonstrated; (iv) direct intracerebral inoculation of A/J mice
      demonstrated lack of neurotoxicity at doses similar to G207, a gamma(1)34.5
      deleted HSV with demonstrated safety in human patient trials and (v) intratumoral
      injection of M012 into Neuro-2a flank tumors in combination with 5-FC
      administration significantly reduced tumor growth versus tumors treated with
      R3659 combined with 5-FC, or treated with M012 alone. Thus, M012 is a promising
      new oncolytic HSV vector with an enhanced prodrug-mediated, antineoplastic effect
      that is safe for intracranial administration.

PMID- 16990847
TI  - Regulation of translation factors eIF4GI and 4E-BP1 during recovery of protein
      synthesis from inhibition by p53.
AB  - Activation of the tumour suppressor protein p53 rapidly inhibits protein
      synthesis. This is associated with dephosphorylation and cleavage of initiation
      factor eIF4GI and the eIF4E-binding protein 4E-BP1. When the activation of p53 is
      reversed within 16 h 4E-BP1 becomes rephosphorylated, the level of intact eIF4GI
      slowly increases and protein synthesis gradually recovers. The recovery of
      protein synthesis is partially blocked by rapamycin and wortmannin but not by the
      protein kinase inhibitors PD98059 and CGP74514A. Both rapamycin and wortmannin,
      but not PD98059 or CGP74514A, delay the reappearance of eIF4GI. In contrast, full
      length 4E-BP1 rapidly becomes rephosphorylated and this process is partially
      inhibited by rapamycin, PD98059 and CGP74514A. Thus, activation of p53 results in
      the inhibition of distinct rapamycin- and wortmannin-sensitive pathways that
      target eIF4GI, and rapamycin-sensitive and -insensitive pathways that target 4E
      BP1. Following inactivation of p53 the gradual recovery is determined largely by
      the kinetics of restoration of eIF4GI rather than by the rephosphorylation of
      full-length 4E-BP1. These findings suggest that the ability of cells to
      rephosphorylate 4E-BP1, resynthesise eIF4GI and restore the rate of protein
      synthesis after inactivation of p53 is an important aspect of recovery following
      the relief of physiological stress.

PMID- 16990848
TI  - Autophagy delays apoptotic death in breast cancer cells following DNA damage.
AB  - Early signaling in camptothecin-treated MCF-7 cells followed an intrinsic
      pathway, but death was delayed and late events exhibited few hallmarks of
      apoptosis. BH3-only proteins, such as Noxa, Puma and BimEL, were activated and
      localized to mitochondrial sites within 24 h following drug exposure. However,
      caspase activity was low and death was unaffected by caspase inhibition.
      Transmission electron micrographs showed the presence of large vacuoles in drug
      treated cells. An autophagic survival response has been attributed to MCF-7 cells
      following nutrient starvation or exposure to tamoxifen. Here, we show that
      autophagy also plays an important role in the delayed DNA damage response.
      Confocal microscopy revealed colocalization of mitochondria with large autophagic
      vacuoles and inhibitors of autophagy increased mitochondrial depolarization and
      caspase-9 activity, and accelerated cell death. Furthermore, downregulation of
      autophagy proteins, Beclin 1 and Atg7, unmasked a caspase-dependent, apoptotic
      response to DNA damage. We propose that a post-mitochondrial caspase cascade is
      delayed as a result of early disposal of damaged mitochondria within
      autophagosomes. Our data also suggest that the use of autophagy as a means of
      delaying apoptosis or prolonging survival may be characteristic of noninvasive
      breast tumor cells. These studies underscore a potential role for autophagy
      inhibitors in combination with conventional chemotherapeutic drugs in early
      breast cancer therapy.

PMID- 16990849
TI  - A network of p73, p53 and Egr1 is required for efficient apoptosis in tumor
      cells.
AB  - p73, a transcription factor rarely mutated in cancer, regulates a subset of p53
      target genes that cause cells to respond to genotoxic stress by growth arrest and
      apoptosis. p73 is produced in two main forms; only TAp73 reiterates the roles of
      p53, while DeltaNp73 can be oncogenic in character. We show that the TAp73 form
      produced by TP73 P1 promoter has five distinct Egr1-binding sites, each
      contributing to the transcriptional upregulation of TAp73 by Egr1 in several cell
      types. In contrast, TP73 P2 promoter transcribes DeltaNp73, is not induced by
      Egr1, but is induced by TAp73 and p53. Induction of TAp73 by genotoxic stress
      requires Egr1 in mouse in vivo. Newly discovered non-consensus p53-binding sites
      in p73, p53 and Egr1 promoters reveal inter-regulating networks and sustained
      expression by feedback loops in response to stress, resulting in prolonged
      expression of the p53 family of genes and efficient apoptosis.

PMID- 16990850
TI  - Dcr2 targets Ire1 and downregulates the unfolded protein response in
      Saccharomyces cerevisiae.
AB  - Accumulation of unfolded proteins in the endoplasmic reticulum triggers the
      unfolded protein response (UPR). How the UPR is downregulated is not well
      understood. Inositol requirement 1 (Ire1) is an endoplasmic reticulum
      transmembrane UPR sensor in Saccharomyces cerevisiae. When the UPR is triggered,
      Ire1 is autophosphorylated, on Ser 840 and Ser 841, inducing the cytosolic
      endonuclease activity of Ire1, thereby initiating the splicing and translational
      de-repression of HAC1 mRNA. Homologous to Atf/Creb1 (Hac1) activates UPR
      transcription. Here, we report that the dose-dependent cell-cycle regulator 2
      (Dcr2) phosphatase functionally and physically interacts with Ire1. We identified
      genetic interactions between DCR2 and genes, including IRE1, which are involved
      in secretory processes. Overexpression of DCR2, but not of a catalytically
      inactive DCR2 allele, significantly delays HAC1 splicing and sensitizes cells to
      the UPR. Furthermore, Dcr2 physically interacts in vivo with Ire1-S840E,S841E,
      which mimics phosphorylated Ire1, and Dcr2 de-phosphorylates Ire1 in vitro. Our
      results are consistent with de-phosphorylation of Ire1 being a mechanism for
      antagonizing UPR signalling.

PMID- 16990851
TI  - The ARP2/3 complex: an actin nucleator comes of age.
AB  - The cellular functions of the actin cytoskeleton require precise regulation of
      both the initiation of actin polymerization and the organization of the resulting
      filaments. The actin-related protein-2/3 (ARP2/3) complex is a central player in
      this regulation. A decade of study has begun to shed light on the molecular
      mechanisms by which this powerful machine controls the polymerization,
      organization and recycling of actin-filament networks, both in vitro and in the
      living cell.

PMID- 16990852
TI  - The COPII cage: unifying principles of vesicle coat assembly.
AB  - Communication between compartments of the exocytic and endocytic pathways in
      eukaryotic cells involves transport carriers - vesicles and tubules - that
      mediate the vectorial movement of cargo. Recent studies of transport-carrier
      formation in the early secretory pathway have provided new insights into the
      mechanisms of cargo selection by coat protein complex-II (COPII) adaptor
      proteins, the construction of cage-protein scaffolds and fission. These studies
      are beginning to produce a unifying molecular and structural model of coat
      function in the formation and fission of vesicles and tubules in endomembrane
      traffic.

PMID- 16990854
TI  - Cysteine cathepsins: multifunctional enzymes in cancer.
AB  - Cysteine cathepsins are highly upregulated in a wide variety of cancers by
      mechanisms ranging from gene amplification to post-transcriptional modification.
      Their localization within intracellular lysosomes often changes during neoplastic
      progression, resulting in secretion of both inactive and active forms and
      association with binding partners on the tumour cell surface. Secreted, cell
      surface and intracellular cysteine cathepsins function in proteolytic pathways
      that increase neoplastic progression. Direct proof for causal roles in tumour
      growth, migration, invasion, angiogenesis and metastasis has been shown by
      downregulating or ablating the expression of individual cysteine cathepsins in
      tumour cells and in transgenic mouse models of human cancer.

PMID- 16990853
TI  - How will HPV vaccines affect cervical cancer?
AB  - Cancer of the uterine cervix is the second largest cause of cancer deaths in
      women, and its toll is greatest in populations that lack screening programmes to
      detect precursor lesions. Persistent infection with 'high risk' genotypes of
      human papillomavirus (HPV) is necessary, although not sufficient, to cause
      cervical carcinoma. Therefore, HPV vaccination provides an opportunity to
      profoundly affect cervical cancer incidence worldwide. A recently licensed HPV
      subunit vaccine protects women from a high proportion of precursor lesions of
      cervical carcinoma and most genital warts. Here we examine the ramifications and
      remaining questions that surround preventive HPV vaccines.

PMID- 16990855
TI  - Ubiquitin and ubiquitin-like proteins in cancer pathogenesis.
AB  - Ubiquitin and ubiquitin-like proteins (Ubls) are signalling messengers that
      control many cellular functions, such as cell proliferation, apoptosis, the cell
      cycle and DNA repair. It is becoming apparent that the deregulation of ubiquitin
      pathways results in the development of human diseases, including many types of
      tumours. Here we summarize the common principles and specific features of
      ubiquitin and Ubls in the regulation of cancer-relevant pathways, and discuss new
      strategies to target ubiquitin signalling in drug discovery.

PMID- 16990856
TI  - Topoisomerase I inhibitors: camptothecins and beyond.
AB  - Nuclear DNA topoisomerase I (TOP1) is an essential human enzyme. It is the only
      known target of the alkaloid camptothecin, from which the potent anticancer
      agents irinotecan and topotecan are derived. As camptothecins bind at the
      interface of the TOP1-DNA complex, they represent a paradigm for interfacial
      inhibitors that reversibly trap macromolecular complexes. Several camptothecin
      and non-camptothecin derivatives are being developed to further increase anti
      tumour activity and reduce side effects. The mechanisms and molecular
      determinants of tumour response to TOP1 inhibitors are reviewed, and rational
      combinations of TOP1 inhibitors with other drugs are considered based on current
      knowledge of repair and checkpoint pathways that are associated with TOP1
      mediated DNA damage.

PMID- 16990857
TI  - Mechanisms of cutaneous toxicities to EGFR inhibitors.
AB  - The increased target specificity of epidermal growth factor receptor (EGFR)
      inhibitors (EGFRIs) is associated with the reduction or abolition of nonspecific
      and haematopoietic side effects. However, coincident inhibition of receptor
      activity in tissues that depend on EGFR signalling for normal function has
      undesirable consequences. Because of the key role of EGFR signalling in skin,
      dermatological toxicities have frequently been described with EGFRIs. The
      resultant significant physical and psycho-social discomfort might lead to
      interruption or dose modification of anticancer agents. There is an urgent need
      for an improved understanding of these toxicities to develop adequate staging
      systems and mechanistically driven therapies, and to ensure quality of life and
      consistent antineoplastic therapy.

PMID- 16990860
TI  - Pure gimmickry.

PMID- 16990858
TI  - The NCI60 human tumour cell line anticancer drug screen.
AB  - The US National Cancer Institute (NCI) 60 human tumour cell line anticancer drug
      screen (NCI60) was developed in the late 1980s as an in vitro drug-discovery tool
      intended to supplant the use of transplantable animal tumours in anticancer drug
      screening. This screening model was rapidly recognized as a rich source of
      information about the mechanisms of growth inhibition and tumour-cell kill.
      Recently, its role has changed to that of a service screen supporting the cancer
      research community. Here I review the development, use and productivity of the
      screen, highlighting several outcomes that have contributed to advances in cancer
      chemotherapy.

PMID- 16990861
TI  - Cinnamaldehyde.

PMID- 16990862
TI  - A financial vacuum.

PMID- 16990863
TI  - Contract daydream.

PMID- 16990865
TI  - Resolving complaints.

PMID- 16990864
TI  - Fruit for ulcers.

PMID- 16990866
TI  - New power.

PMID- 16990867
TI  - BDA for DCPs.

PMID- 16990868
TI  - Unwanted effects.

PMID- 16990869
TI  - Prescribing patterns.

PMID- 16990870
TI  - Gaps in the curriculum.

PMID- 16990871
TI  - Jig relief.

PMID- 16990872
TI  - Learn from America.

PMID- 16990883
TI  - Treatment planning of the edentulous mandible.
AB  - Edentulism can be a debilitating handicap. Zarb described endentulous individuals
      who could not function as 'denture cripples'.(1) Most difficulty with complete
      denture prostheses arises from the inability to function with the mandibular
      prostheses. Factors that adversely affect successful use of a complete denture on
      the mandible include: 1) the mobility of the floor of the mouth, 2) thin mucosa
      lining the alveolar ridge, 3) reduced support area and 4) the motion of the
      mandible (Figs 1,2). These factors alone can explain the difficulty of wearing a
      denture on the mandibular arch compared to the maxillary arch. The maxilla
      exhibits much less mobility on the borders of the denture than the mandible,
      moreover having a stable palate with thick fibrous tissues available to support
      the prostheses and resist occlusal forces. These differences explain most of the
      reasons why patients experience difficulty with using a complete denture on the
      mandibular arch compared to the maxillary arch.

PMID- 16990884
TI  - Metastatic breast carcinoma discovered in a dentigerous cyst - a case report.
AB  - This paper reports a patient with a history of breast cancer, who presented with
      altered sensation to the right lower lip and chin. An orthopantomogram showed a
      probable dentigerous cyst associated with an unerupted lower wisdom tooth, which
      was closely related to the inferior dental canal. The tooth and cyst were
      enucleated under general anaesthesia. The subsequent histopathology report
      concluded that the cyst contained metastatic adenocarcinoma from a primary breast
      tumour.

PMID- 16990889
TI  - The feminisation of the orthodontic workforce.
AB  - OBJECTIVE: To describe the status and activity of women in the UK orthodontic
      workforce. DESIGN AND SETTING: Postal questionnaire based on the UK orthodontic
      workforce. SUBJECTS: All orthodontic providers in the UK. MATERIALS AND METHODS:
      A questionnaire was circulated to the total study population. The variables
      studied relating to sex were numbers, age, number of sessions worked,
      productivity, professional status and retirement intentions. RESULTS: The
      response rate was 72.7%. 31.4% of the participants were female. The average age
      of female providers was 42.7 (SE 0.48) years, who were on average 4 years younger
      than males. Sixty-six percent of specialist trainees are women and 34% men. 41.5%
      of male providers and 31.6% of female providers plan to retire in the next 15
      years. The mean number of sessions worked by women was 7.2 (SE 0.1) and men 8.2
      (SE 0.1). Women completed 24.2 (SE 1.9) cases per session and men 25.6 (SE 1.3).
      CONCLUSIONS: The orthodontic workforce is becoming increasingly feminised. The
      cumulative effect of more women completing fewer cases will mean that workforce
      planners will need to consider increasing numbers to allow for this feminisation.

PMID- 16990890
TI  - The relationship between NHS patient charges and the uptake of dental
      examinations by Scottish adults 1982-1998.
AB  - OBJECTIVE: The aim of this study was to determine if increasing cost to the
      patient of an NHS dental examination was associated with a change in the uptake
      of dental examinations by Scottish adults aged 18 years and over. The null
      hypothesis was that there was no significant difference (a = 0.05) in the number
      of NHS dental examinations taken up by Scottish adults with increase in cost to
      the patient. METHOD: Data for this retrospective study of cost and dental
      attendance between 1982-1998 was collected from the British Dental Association
      and Scottish Dental Practice Division. The number of examinations per month per
      dentist was calculated for the years 1982-1998 as an indicator of dental
      attendance. RESULTS: The reported number of NHS dental examinations increased by
      34% between 1982 and 1998 from 1,564,330 to 2,099,944. However the reported
      number of general dental practitioners working in the NHS in Scotland increased
      by 48% from 1362 to 2012. The number of examinations per month per dentist
      decreased from 95.71 in 1982 to 86.98 in 1998. CONCLUSION: There was a
      significant (p = 0.001) reduction of 7.6% in the number of examinations per month
      per dentist after the introduction of charges. However within the charged data,
      while there is still a reduction, it was not significant. Other cost related
      factors may be influencing dental attendance and should be considered.

PMID- 16990891
TI  - Dental implantology education: a survey of opinion and experience of 106 general
      dental practitioners.
AB  - In the United Kingdom the National Health Service only provides dental implant
      treatment to patients who fulfil stringent clinical criteria outlined by the
      Royal College of Surgeons. Such treatment is normally in a hospital setting. The
      majority of dental implant work is otherwise carried out in the private sector.
      Concern about the quality of implant dentistry and training led the General
      Dental Council to convene a working group that set out to set training standards
      in implant dentistry for general dental practitioners (GDPs). The Faculty of
      General Dental Practitioners published this guidance in March 2006. This
      questionnaire based study set out to examine GDP attitudes to implant treatment
      and training and aims to contribute to the debate and review of appropriate
      training in dental implantology for GDPs.

PMID- 16990892
TI  - Conscious sedation training received by specialist registrars in restorative
      dentistry in the UK: a survey.
AB  - OBJECTIVE: To investigate conscious sedation training received by Specialist
      Registrars in Restorative Dentistry (SpRs) during their training programme.
      DESIGN: Postal questionnaire survey in the UK. Setting SpRs and recently
      certificated Consultants in Restorative Dentistry (CRDs). METHOD: A questionnaire
      was sent to 81 current SpRs in Restorative Dentistry and CRDs who had been
      awarded a Certificate of Completion of Specialist Training within the previous
      three years. One follow-up letter was sent to non-responders. RESULTS: The
      completed questionnaire was returned by 67 (83%) SpRs and CRDs. Analysis revealed
      that 44 (69%) respondents had received conscious sedation training during their
      specialist training programme and that 50 (78%) respondents carried out
      restorative dental treatment under sedation during their programme. Thirteen
      (20%) respondents had not received conscious sedation training in their
      programmes but eight (13%) SpRs indicated that sedation training was planned.
      Training experiences differed throughout the UK: 29 (66%) respondents gained
      experience in inhalational and single agent intravenous sedation techniques under
      the supervision of an experienced colleague. Fourteen (32%) respondents who
      performed sedation had not been on a resuscitation course in the previous year.
      These included nine (21%) current SpRs. Sixteen (53%) current SpRs intended to
      offer restorative dental treatment under sedation after specialist training.
      Fifty-nine (92%) respondents thought that all SpRs in Restorative Dentistry
      should receive sedation training and 42 (71%) thought that a structured core
      course would be the most appropriate format. CONCLUSIONS: Although the majority
      of SpRs and recently certificated CRDs considered that all SpRs should receive
      training in conscious sedation via a core course during the restorative dentistry
      training programme, a small number had not received or planned to undertake such
      training. Conscious sedation training experiences differed throughout the UK and
      SpRs treated a wide range of deserving patient categories under sedation. It is
      encouraging that many SpRs hope to continue employing sedation techniques after
      their restorative dentistry training has finished. The results of this survey
      should inform all those involved with restorative dentistry training programmes.

PMID- 16990924
TI  - Aliens or colleagues? Refugees from Nazi oppression 1933-1945.

PMID- 16990927
TI  - SPRAWL IN THE 1990S Measurement, Distribution, and Trends.
AB  - Although sprawl is a growing national debate, there have been few efforts to
      measure or monitor changes in degree of sprawl over time. By using a methodology
      that employs census data, this sprawl index allows computation of levels of
      sprawl and examination of temporal and geographic changes. The results show that
      sprawl has increased over the past decade in many metropolitan areas. There are
      important geographic variations in sprawl, implying that it is neither inevitable
      nor universal.

PMID- 16990928
TI  - Creating carbon-carbon bonds with samarium diiodide for the synthesis of modified
      amino acids and peptides.
AB  - In this perspective, an overview of our experiences on the application of
      samarium diiodide in organic synthesis for the preparation of amino acid and
      peptide analogues is presented. Three different carbon-carbon bond forming
      reactions are discussed, including side chain introductions, gamma-amino acid
      synthesis and acyl-like radical additions for the construction of C-C mimics of
      the peptidic bonds.

PMID- 16990929
TI  - Rapamycin biosynthesis: Elucidation of gene product function.
AB  - The function of gene products involved in the biosynthesis of the clinically
      important polyketide rapamycin were elucidated by biotransformation and gene
      complementation.

PMID- 16990930
TI  - Hydroxide-ion binding to nonionic interfaces in aqueous solution.
AB  - The mechanism of hydroxide ion binding to nonionic surfaces is explored by
      variation of the properties of the water-aggregate interface and by variation of
      the type of the aggregate.

PMID- 16990931
TI  - Asymmetric hydrogenation with antibody-achiral rhodium complex.
AB  - Monoclonal antibodies have been elicited against an achiral rhodium complex and
      this complex was used in the presence of a resultant antibody, 1G8, for the
      catalytic hydrogenation of 2-acetamidoacrylic acid to produce N-acetyl-L-alanine
      in high (>98%) enantiomeric excess.

PMID- 16990932
TI  - Synthesis of a versatile multifunctional building block for the construction of
      polyketide natural products containing ethyl side-chains.
AB  - The synthesis of a multifunctional building block for polyketide construction and
      several subsequent reactions are presented.

PMID- 16990933
TI  - Chemical synthesis of picornaviral protein primers of RNA replication.
AB  - Naturally occurring nucleopeptidic replication primers (VPg-pUpU) of poliovirus
      and coxsackie virus were chemically synthesized. The synthesis was accomplished
      via block-coupling of two minimally protected fragments of the target structures:
      a short RNA-nucleopeptide and a longer peptide segment containing diverse side
      chain functionalities. The synthetic VPg-pUpU of coxsackie virus was
      characterized by NMR spectroscopy.

PMID- 16990934
TI  - Synthesis and structural investigations of N-alkylated beta-peptidosulfonamide
      peptide hybrids of the amyloidogenic amylin(20-29) sequence: Implications of
      supramolecular folding for the design of peptide-based bionanomaterials.
AB  - The incorporation of a single beta-aminoethane sulfonyl amide moiety in a highly
      amyloidogenic peptide sequence resulted in a complete loss of amyloid fibril
      formation. Instead, supramolecular folding morphologies were observed. Subsequent
      chemoselective N-alkylation of the sulfonamide resulted in amphiphilic peptide
      based hydrogelators. It was found that variation of merely the alkyl chain
      induced a dramatic variation in aggregation motifs such as helical ribbons and
      tapes, ribbons progressing to closed tubes, twisted lamellar sheets and
      entangled/branched fibers.

PMID- 16990935
TI  - The design and synthesis of inhibitors of pantothenate synthetase.
AB  - Pantothenate synthetase catalyses the ATP-dependent condensation of D-pantoate
      and beta-alanine to form pantothenate. Ten analogues of the reaction intermediate
      pantoyl adenylate, in which the phosphodiester is replaced by either an ester or
      sulfamoyl group, were designed as potential inhibitors of the enzyme. The esters
      were all modest competitive inhibitors, the sulfamoyls were more potent,
      consistent with their closer structural similarity to the pantoyl adenylate
      intermediate.

PMID- 16990936
TI  - Synthesis and evaluation of potential CT (computer tomography) contrast agents
      for bone structure and microdamage analysis.
AB  - The design and synthesis of several novel X-ray contrast agents 1-3, developed
      for targeting bone structures, and in particularly microcracks in bones, using CT
      (Computer Tomography) detection is described. These contrast agents are based on
      the use of the well known triiodobenzene platform, which was conjugated into one
      or more phenyliminodiacetate moieties, which can be used to 'lock' onto bone
      matrices. Compounds 1-3 were all tested for their ability to visualise cracks in
      bone structures (bovine bones) using micro-CT imaging.

PMID- 16990937
TI  - Photoswitch inhibitors of alpha-chymotrypsin--increased substitution and peptidic
      character in peptidomimetic boronate esters.
AB  - A series of peptidomimetic boronate esters containing the photoisomerisable
      azobenzene group has been synthesised and assayed against the serine protease
      alpha-chymotrypsin. Compounds with borophenylalanine inhibition groups were found
      to be inhibitors with micromolar activity, while those with aryl boronate
      inhibition groups were inactive. Selected compounds were isomerised by UV or
      visible light to obtain enriched states of the (Z) or (E) isomers, respectively,
      and assayed. A change in activity on photoisomerisation was observed, however
      some decomposition of the boronate group on irradiation was also observed,
      limiting reversibility.

PMID- 16990938
TI  - Internally quenched peptides for the study of lysostaphin: An antimicrobial
      protease that kills Staphylococcus aureus.
AB  - Lysostaphin (EC. 3.4.24.75) is a protein secreted by Staphylococcus simulans
      biovar staphylolyticus and has been shown to be active against methicillin
      resistant S. aureus (MRSA). The design and synthesis of three internally quenched
      substrates for lysostaphin based on the peptidoglycan crossbridges of S. aureus,
      and their use in fluorescence resonance energy transfer (FRET) assays is
      reported. These substrates enabled the gathering of information about the
      endopeptidase activity of lysostaphin and the effect that mutations have on its
      enzymatic ability. Significant problems with the inner filter effect and
      substrate aggregation were encountered; their minimisation and the subsequent
      estimation of the kinetic parameters for the interaction of lysostaphin with the
      substrates is described, as well as a comparison of substrates incorporating two
      FRET pairs: Abz-EDDnp and DABCYL-EDANS. In addition to this, the points of
      cleavage caused by lysostaphin in Abz-pentaglycine-EDDnp have been determined by
      HPLC and mass spectrometry analysis to be between glycines 2 and 3(approximately
      60%) and glycines 3 and 4 (approximately 40%).

PMID- 16990939
TI  - Synthesis of orthogonally protected biaryl amino acid derivatives.
AB  - The efficient and direct synthesis of protected biaryl amino acids, including
      dityrosine (50% overall yield over 3 steps), by Negishi cross-coupling of the
      serine-derived organozinc reagent 4 with iodo- and di-iodobiaryls, is reported.
      An improved, although still not perfect, diiodination of 2,2'-biphenol has been
      achieved using NMe3BnICl2-ZnCl2. Protection of phenolic hydroxyl groups as
      acetates, rather than benzyl ethers, is required for efficient cross-coupling,
      and evidence for acetyl migration has been observed during debenzylation of a
      substituted 2-acetoxy-2'-benzyloxybiaryl. Aromatic C-I to C-Cl conversion has
      been detected as a minor reaction pathway in the palladium-catalyzed coupling of
      aryl iodide 3b with organozinc reagent 4.

PMID- 16990940
TI  - Synthesis of a C-linked glycosylated thymine-based PNA monomer and its
      incorporation into a PNA oligomer.
AB  - Backbone modification of peptide nucleic acids (PNAs) by glycosylation has been
      shown to enhance selective biodistribution and cellular targeting of PNA
      oligomers based on sugar and cell surface lectin interactions. Here we report the
      synthesis of a new backbone-glycosylated thymine-based PNA monomer (T(gal)). The
      sugar residue was attached to the backbone of PNA via a stable carbon-carbon
      linkage between the sugar and the PNA monomers. Also, incorporation of the
      modified monomer into a PNA decamer (H-Ala(gal)-G-G-G-T(gal)-C-A-G-C-T(gal)-T-Lys
      NH2) was successfully performed. Melting temperature (UV-Tm) of the modified PNA
      against the complementary DNA was only slightly lower than unmodified PNA.

PMID- 16990941
TI  - Selective product amplification of thymine photodimer by recognition-directed
      supramolecular assistance.
AB  - Two symmetric ditopic supramolecular templates (1 and 2) each presenting two
      hydrogen bonding recognition subunits were synthesized. Each such subunit
      comprises the same donor and acceptor pattern, capable of binding a substrate
      molecule with complementary hydrogen bonding groups to form a supramolecular
      complex. Substrate molecules, such as thymine or uracil derivatives, yield 2 : 1
      complexes with the acceptors involving two hydrogen bonds to each subunit with
      ideal orientation for subsequent [2 + 2] dimerization upon photoirradiation.
      Selective syn photoproduct formation and concomitant suppression of the trans
      isomer are favored by orientation of the two guest nucleobases within the
      template cleft. Complementary donor and acceptor hydrogen bonding induced
      positioning of the two substrates and steric hindrance within the template clefts
      are responsible for the selective product formation.

PMID- 16990942
TI  - An efficient one-pot, three-component synthesis of indeno[1,2-b]quinoline
      9,11(6H,10H)-dione, acridine-1,8(2H,5H)-dione and quinoline-3-carbonitrile
      derivatives from enaminones.
AB  - An efficient one-pot, three-component method for the preparation of indeno[1,2
      b]quinoline-9,11(6H,10H)-dione, acridine-1,8(2H,5H)-dione and various multi
      substituted quinoline-3-carbonitrile derivatives has been developed through the
      Michael addition to enaminones, which was achieved by both microwave irradiation
      and conventional heating.

PMID- 16990943
TI  - Methyltrifluoropyruvate imines possessing N-oxalyl and N-phosphonoformyl groups-
      precursors to a variety of alpha-CF3-alpha-amino acid derivatives.
AB  - Convenient routes to methyl 2-oxalylimino- and 2-(phosphonoformimido)-3,3,3
      trifluoropropanoates have been elaborated, based on the reaction of methyl
      trifluoropyruvate with ethyl oxamate or diethyl carbamoylphosphonate,
      respectively, followed by dehydration. The compounds obtained are useful
      synthetic intermediates toward a variety of novel 3,3,3-trifluoroalanine
      derivatives that are potential drug candidates.

PMID- 16990944
TI  - Polyhydroxylated homoazepanes and 1-deoxy-homonojirimycin analogues: Synthesis
      and glycosidase inhibition study.
AB  - The Johnson-Claisen rearrangement of D-gluco and L-ido-derived allylic
      orthoesters afforded gamma,delta-unsaturated ester that on ester reduction,
      epoxidation, regioselective oxirane opening by sodium azide and hydrogenation led
      to sugar amino alcohols--immediate precursors for 1-deoxy-homonojirimycin 3a,b,
      and polyhydroxylated homoazepanes 4a,b. Our synthetic approach and glycosidase
      inhibitory activity is reported.

PMID- 16990945
TI  - New regiospecific isothiazole C-C coupling chemistry.
AB  - Regioselective palladium catalysed coupling reactions are achieved in good to
      high yields, starting from either 3,5-dichloro- or 3,5-dibromoisothiazole-4
      carbonitriles 1 and 2, providing 3-halo-5-(hetero/aryl, alkenyl and
      alkynyl)isothiazoles 3, 4, 6-9 from Stille couplings, 3-halo-5
      (hetero/arylethynyl)isothiazoles 14-19 from Sonogashira and 5,5'-bi(3
      chloroisothiazole-4-carbonitrile) (13) from an Ullmann type coupling. 3,5
      Dibromoisothiazole-4-carbonitrile 2 is more reactive than the dichloroisothiazole
      4-carbonitrile 1 and effective enough for Stille, Negishi and Sonogashira
      couplings. 5,5-Bi(3-chloroisothiazole-4-carbonitrile) (13) is prepared by a
      palladium catalysed Ullmann coupling from 3-chloro-5-iodoisothiazole-4
      carbonitrile (11). A variety of 3-substituted isothiazoles (3-substituents = Cl,
      Br, OMs, OTs and OTf) are less reactive and fail to give successful Suzuki
      couplings at the isothiazole C-3 position. The 3-iodo-5-phenyl-isothiazole-4
      carbonitrile (28), prepared via Sandmeyer iodination, participates successfully
      in Suzuki, Ullmann type, Stille, Negishi and Sonogashira coupling reactions. All
      products are fully characterized.

PMID- 16990946
TI  - Exploitation of sugar ring flipping for a hinge-type tether assisting a [2 + 2]
      cycloaddition.
AB  - Methyl 3-O-p-methoxybenzyl-beta-D-xylopyranoside (2) was exploited as a novel
      hinge-type tether for the [2 + 2] cycloaddition of cinnamate. The major ring
      conformation occupied by the 2,4-dicinnamate derivative of 2 was 4C1, which
      extends two cinnamates along a diequatorial orientation. However, 3-O-deprotected
      dicinnamate 5, when in a non-polar solvent, favours the 1C4 conformation, which
      assists the approach of two cinnamates with the 1,3-diaxial scaffold.
      Photoirradiation of compound at 313 nm in CHCl3 afforded the intramolecular
      cycloaddition of cinnamates to give methyl beta-, delta-, and xi-truxinates in a
      86 : 8 : 6 ratio after transesterification with methanol. The regio- and
      stereoselectivities are comparable to those reported by others for tethered
      cinnamates. The per-deuterated dicinnamate derivative of 5 facilitated the
      conformation analyses of the pyranoside rings by 1H NMR, indicating that all the
      products of photoirradiation had 1C4-fixed pyranosides. Excellent beta
      selectivity was achieved when m-bromocinnamate was subjected to hinge-tethered [2
      + 2] cycloaddition.

PMID- 16990947
TI  - Influence of microwave radiation on free Candida antarctica lipase B activity and
      stability.
AB  - The influence of microwave heating on free Candida antarctica lipase B activity
      and stability was studied over the temperature range from 40 to 110 degrees C.
      Concerning the lipase activity, identical initial rate and conversion yield were
      obtained under microwave radiation and classical thermal heating for the
      alcoholysis between ethyl butyrate and butanol in a solvent-free system. On the
      other hand, the kinetics of the free lipase inactivation in butanol appears to be
      influenced by the heating mode. The Arrhenius plot obtained under classical
      heating was linear over all the temperature range studied whereas a biphasic
      Arrhenius plot was obtained under microwaves. The non-classical effect of the
      microwave heating on the initial rate of the enzymatic inactivation was thus
      dependent on the temperature of incubation.

PMID- 16990948
TI  - Cryopreservation of spermatozoa of black marlin, Makaira indica (Teleostei:
      Istiophoridae).
AB  - As a first step towards the development of a method for the cryopreservation of
      black marlin spermatozoa, this study investigated the effect of dimethylsulfoxide
      (DMSO) concentration and pellet size on post-thaw spermatozoal motility.
      Spermatozoa were recovered from the spermatic duct of testes retrieved post
      mortem from four adult black marlin caught in the Coral Sea spawning grounds of
      Australia. Undiluted spermatozoa were stored on ice for 4 to 10 hours during
      transport to shore, then evaluated for motility after activation in seawater
      (1:10 v:v). Spermatozoa were prepared for cryopreservation in pellets by
      extension (1:3 v:v) in a defined fish Ringer's solution to give two final DMSO
      concentrations of 2.5% or 5.0%. Diluted spermatozoa were frozen directly on a dry
      ice block in pellet sizes of either 0.25 ml or 0.50 ml. Frozen pellets were
      thawed in a water bath at 40 degrees C for 60 seconds and assessed for post-thaw
      motility following activation in seawater. Spermatozoa recovered within 50
      minutes of death and chilled on ice for 4 to 10 hours showed a mean (+/- SEM)
      motility immediately following activation of 91.6 +/- 7.9%. 50% of the
      spermatozoa remained motile for approximately 4 to 5 minutes. Following
      cryopreservation, mean motility declined significantly across all cryoprotectant
      and pellet size combinations (P < 0.001) but spermatozoa frozen in 2.5% DMSO
      showed higher motility than those frozen in 5.0% DMSO (P = 0.014). Pellet size
      had no effect on post-thaw motility (P = 0.179).

PMID- 16990950
TI  - Cryopreservation of potato cultivated varieties and wild species: critical
      factors in droplet vitrification.
AB  - The applicability of cryopreservation protocols to a broad range of genotypes is
      a key issue for genebanks. We tried to identify the critical factors causing
      differences in survival of cryopreserved shoot tips using potato varieties coming
      from cultivated and wild species. The droplet-vitrification method, a combination
      of droplet-freezing and solution-based vitrification, was selected from several
      protocols. High survival after freezing was observed after dehydration with PVS2
      for 20 min, cooling shoot tips placed in a droplet of PVS2 solution on aluminum
      foil strips by immersing the foil strips in liquid nitrogen, warming them by
      plunging the foil strips into a 0.8 M sucrose solution (at 40 degrees C) for 30 s
      and unloading in 0.8 M sucrose for 30 min. This optimized protocol was
      successfully applied to 12 accessions with survival ranging between 64.0 and
      94.4%.

PMID- 16990949
TI  - Cryopreservation of cultivated and wild potato varieties by droplet
      vitrification: effect of subculture of mother-plants and of preculture of shoot
      tips.
AB  - In this paper, we studied the effect of subculture of mother-plants and of
      preculture of shoot tips of two potato varieties (Dejima, cultivated and STN13,
      wild) cryopreserved using the droplet-vitrification technique. The subculture
      conditions (light intensity, aeration and planting density) significantly
      affected survival of both non-cryopreserved and cryopreserved shoot-tips in both
      varieties. The subculture duration and the position of the shoot tips on the axis
      of the in vitro plantlets had a significant (P<0.0001) effect on survival of
      cryopreserved shoot tips. The optimal subculture duration was 7 and 5 weeks and
      the optimal size of shoot tips was 1.5-2.0 and 1.0-1.5 mm for var. Dejima and
      STN13, respectively. Survival of cryopreserved shoot tips was influenced by the
      sucrose concentration in the preculture medium and the preculture duration. The
      highest survival of cryopreserved shoot tips was observed after preculture with
      0.3 M sucrose for 8 h followed by 0.7 M sucrose for 18 h. These results indicate
      that the parameters of the subculture of mother-plants and of preculture of shoot
      tips should be carefully optimized, especially in the case of wild species.

PMID- 16990951
TI  - Cryopreservation of seeds and in vitro-cultured protocorms of Oncidium bifolium
      sims. (Orchidaceae) by encapsulation-dehydration.
AB  - Encapsulation-dehydration was employed for cryopreserving seeds and in vitro
      cultured protocorms of Oncidium bifolium. Freshly harvested seeds, 120 days after
      pollination, were encapsulated in beads containing 1/2 MS medium with 3% sucrose
      and 3% calcium alginate and subsequently pretreated in agitated (80 rpm) liquid
      medium supplemented with 0.15 M sucrose (24 h) followed by 0.25 M sucrose (48 h),
      0.5 M sucrose (24 h) and 0.75 M sucrose (24 h). The beads with seeds were
      dehydrated with silica gel for 5 h to 19.2% moisture content and immersed in
      liquid nitrogen for 1 h, thawed at 30 degrees C for 2 min, post-treated using the
      same series of liquid media [0.5 M sucrose (24 h), 0.25 M sucrose (48 h), 0.15 M
      sucrose (24 h)], and recultured on 1/2 MS medium with 0.1M sucrose and 0.7%
      percent agar. As much as 4.8% of the cryopreserved seeds produced complete
      plants. In-vitro cultured protocorms were successfully cryopreserved following
      the same procedure, allowing 11.3% of them to produce plants.

PMID- 16990952
TI  - Numerical simulation of tissue freezing by liquid nitrogen based cryoprobe.
AB  - A model is presented to simulate the cooling processes during tumor cryosurgery
      with different kinds of flows through the cryoprobe. The heat flux between the
      cryoprobe wall and the tumor, the heat transfer coefficient under different
      inflow conditions are obtained numerically. The impact of the inlet mass flow
      rate, gas volume fraction on these parameters is investigated. It is found that
      the heat transfer coefficient decreased significantly when inflow changed from
      two-phase annular flow to droplet flow, and to gas flow. The inlet gas volume
      fraction and flow velocity only significantly affect the freezing ability of the
      probe when the inflow is gas or in droplet phase. Simulation of the tumor
      temperature profiles under different flow conditions show that the heat transfer
      coefficient is a crucial parameter in temperature prediction during cryosurgery.
      Results indicate that when the cryoprobe wall is assumed at a constant
      temperature conventionally, the cooling effect could be overestimated. It would
      be more reasonable to use the constant wall heat transfer coefficient to simulate
      the cooling progress under a specific flow.

PMID- 16990953
TI  - Actin localisation and the effect of cytochalasin D on the osmotic tolerance of
      cauda epididymidal kangaroo spermatozoa.
AB  - This study examined the hypothesis that filamentous actin associated with the
      complex cytoskeleton of the kangaroo sperm head and tail may be contributing to
      lack of plasma membrane plasticity and a consequent loss of membrane integrity
      during cryopreservation. In the first study, the distribution of G and F actin
      within Eastern Grey Kangaroo (EGK, Macropus giganteus) cauda epididymidal
      spermatozoa was successfully detected using DNAse-FITC and a monoclonal F-actin
      antibody (ab205, Abcam), respectively. G-actin staining was most intense in the
      acrosome but was also observed with less intensity over the nucleus and mid
      piece. F-actin was located in the sperm nucleus but was not discernable in the
      acrosome or sperm tail. To investigate whether cytochalasin D (a known F-actin
      depolymerising agent) was capable of improving the osmotic tolerance of EGK cauda
      epididymal spermatozoa, sperm were incubated in hypo-osmotic media (61 and 104
      mOsm) containing a range of cytochalasin D concentrations (0-200 microM).
      Cytochalasin D had no beneficial effect on plasma membrane integrity of sperm
      incubated in hypo-osmotic media. However, when EGK cauda epididymidal sperm were
      incubated in isosmotic media, there was a progressive loss of sperm motility with
      increasing cytochalasin D concentration. The results of this study indicated that
      the F-actin distribution in cauda epididymidal spermatozoa of the EGK was
      surprisingly different from that of the Tammar Wallaby (M. eugenii) and that
      cytochalasin-D does not appear to improve the tolerance of EGK cauda epididymidal
      sperm to osmotically induced injury.

PMID- 16990954
TI  - Cryopreservation of rabbit spermatozoa with freezing media supplemented with
      reduced and oxidised glutathione.
AB  - This study researches the effects of supplementation with reduced glutathione
      (GSH, 0.5 mm) and oxidised glutathione (GSSG, 0.5 mM) freezing extenders on
      different semen parameters after equilibration with DMSO preservation solution
      (45 min at 5 degrees C) and post-thawing. The main findings that emerged from
      this study are that (i) addition of GSH and GSSG to the freezing media did not
      result in any improvement in functional sperm tests after equilibrium phase. (ii)
      No differences were observed after cryopreservation in functional sperm tests and
      embryo recovery rate. In conclusion, the addition of 0.5 mM GSH or GSSG appears
      not to play an important role in sperm antioxidant defence during cooling and
      freezing in rabbit spermatozoa.

PMID- 16990955
TI  - Health screening packages: the place of measuring C-reactive protein.

PMID- 16990956
TI  - Common modalities for routine antepartum foetal monitoring: are they evidence
      based?
AB  - Antepartum foetal monitoring is crucial for the detection of foetuses at risk so
      that timely intervention can improve the perinatal outcome. The evidence
      underlying the most common modalities of antepartum foetal monitoring used are
      appraised and presented in this article. Foetal movement chart should be used in
      high-risk pregnancies but not recommended routinely in low-risk pregnancies.
      Symphysis-fundal height measurement, being associated with low cost and ease of
      use, is a reasonable screening tool for foetal well-being. Third trimester
      ultrasonography is, thus far, the best modality available for the assessment of
      foetal growth, and can be used until a better modality for foetal growth
      assessment becomes available. Antepartum cardiotocography can be used to monitor
      foetal well-being in normal pregnancies beyond the estimated date of delivery but
      it probably serves little purpose prior to that. Well-designed controlled studies
      evaluating modalities for antepartum foetal monitoring are generally lacking.
      With the advance of medical science, more research should be focused on this
      aspect of obstetric care so that our practice can become more evidence-based.

PMID- 16990957
TI  - Should high sensitive C-reactive protein measurement be included in health
      screening packages?
AB  - INTRODUCTION: The Centers for Disease Control and Prevention (CDC) and the
      American Heart Association (AHA) have endorsed the optional use of high sensitive
      C-reactive protein (hsCRP) to identify patients without known coronary heart
      disease but who may be at higher absolute risk than estimated by major risk
      factors. This study assessed the potential value of hsCRP measurement in addition
      to routine lipid and risk factor assessment on patient management for individuals
      undergoing multiphasic health screening. METHODS: hsCRP was measured on fasting
      lipid samples on patients attending the Health Enrichment Clinic at Tan Tock Seng
      Hospital between January and April 2004. These results were then compared with
      the outcome of individual patient risk assessment (using the 2001 Singapore
      Ministry of Heath Clinical Practice Guidelines on Lipids), the patient's lipid
      results and whether the patient was already on anti-lipid treatment. RESULTS: 212
      samples were analysed for hsCRP. Seven patients were already on anti-lipid drugs.
      Using the AHA/CDC guidelines, hsCRP measurement would be of value in deciding
      management in 12.7 percent of all patients. Of this group, 11 percent had hsCRP
      concentrations in the high risk category. Restricting hsCRP measurement to only
      those patients with two or more cardiac risk factors and not on anti-lipid drugs
      would increase the proportion of patients where hsCRP could be useful in deciding
      management, to 81.8 percent. CONCLUSION: For clinicians prepared to consider
      treatment in patients with elevated hsCRP levels, hsCRP measurement should be
      included as part of health screening packages to selected patients based on
      individual cardiac risk assessment.

PMID- 16990958
TI  - Changes in the levels of major cardiovascular risk factors in the multi-ethnic
      population in Singapore after 12 years of a national non-communicable disease
      intervention programme.
AB  - INTRODUCTION: The National Healthy Lifestyle Programme, a population-wide non
      communicable disease intervention programme, was started in 1992. A National
      Health Survey is carried out every six years to evaluate the impact of this
      programme on the cardiovascular risk factor profile of the resident population of
      Singapore. METHODS: The 2004 National Health Survey (NHS 04) was a population
      based survey carried out over a period of four months from September to December
      2004. A combination of disproportionate stratified sampling and systematic
      sampling was used to select a representative sample (n=7,078) for the survey. The
      reference population comprised 2.4 million multi-racial Singaporeans aged 18-69
      years. Anthropometric and blood pressure measurements were carried out on all
      subjects and blood samples were taken for biochemical analysis. The results were
      compared with those of a similar survey conducted in 1998. RESULTS: A total of
      4,084 Singapore residents took part in the survey, giving a response rate of 57.7
      percent. The age-standardised prevalence of hypertension (greater than or equal
      to 140/90 mmHg) in Singapore residents aged 30-69 years decreased from 28.0
      percent in 1998 to 24.0 percent (p-value is less than 0.001) in 2004. The
      prevalence of high total cholesterol (greater than or equal to 6.2 mmol/L) among
      those aged 18-69 years fell from 26.0 percent in 1998 to 18.1 percent (p-value is
      less than 0.001) in 2004. The prevalence of diabetes mellitus in residents aged
      18-69 years in 2004 was 7.8 percent, compared to the 1998 level of 9.5 percent (p
      value is less than 0.01). The level of obesity (body mass index is greater than
      or equal to 30 kg/sqm) increased slightly from 6.2 percent in 1998 to 6.8 percent
      (p-value equals 0.1627). The prevalence of daily smoking decreased from 15.0
      percent in 1998 to 12.5 percent in 2004 (p-value is less than 0.001), while that
      of regular exercise increased from 17.0 percent to 25.0 percent (p-value is less
      than 0.001). Ethnic differences in the prevalence of diabetes mellitus,
      hypertension, hypercholesterolaemia, and exercise were observed. CONCLUSION: The
      NHS 04 results suggest that the National Healthy Lifestyle Programme
      significantly decreased daily smoking, high blood cholesterol and hypertension,
      and increased regular exercise over 1998 levels. The results also suggest that
      the programme stabilised the prevalence of obesity and diabetes mellitus.

PMID- 16990959
TI  - Breast carcinomas: why are they missed?
AB  - INTRODUCTION: Mammography has proven to be an effective modality for the
      detection of early breast carcinoma. However, 4-34 percent of breast cancers may
      be missed at mammography. Delayed diagnosis of breast carcinoma results in an
      unfavourable prognosis. The objective of this study was to determine the causes
      and characteristics of breast carcinomas missed by mammography at our
      institution, with the aim of reducing the rate of missed carcinoma. METHODS: We
      reviewed the reports of 13,191 mammograms performed over a five-year period.
      Breast Imaging Reporting and Data Systems (BI-RADS) were used for the
      mammographical assessment, and reports were cross-referenced with the
      histological diagnosis of breast carcinoma. Causes of missed carcinomas were
      classified. RESULTS: Of 344 patients who had breast carcinoma and had mammograms
      done prior to surgery, 18 (5.2 percent) failed to be diagnosed by mammography. Of
      these, five were caused by dense breast parenchyma obscuring the lesions, 11 were
      due to perception and interpretation errors, and one each from unusual lesion
      characteristics and poor positioning. CONCLUSION: Several factors, including
      dense breast parenchyma obscuring a lesion, perception error, interpretation
      error, unusual lesion characteristics, and poor technique or positioning, are
      possible causes of missed breast cancers.

PMID- 16990960
TI  - Cinnamon bark extract improves glucose metabolism and lipid profile in the
      fructose-fed rat.
AB  - INTRODUCTION: The present study was designed to investigate whether cinnamon bark
      extract (CBEt) mitigates the adverse effects of fructose loading on glucose
      metabolism and lipid profile in rats. METHODS: Adult male albino rats of body
      weight 150-170 g were divided into five groups and fed with either control or
      high fructose diet (HFD). CBEt was administered to HFD-fed rats orally at two
      doses (a low and a high dose) while the control diet-fed rats were treated with a
      high dose of CBEt. The treatment protocol was carried out for 60 days after which
      the oral glucose tolerance test was carried out. Biochemical parameters related
      to glucose metabolism and lipid profile were assayed. RESULTS: The levels of
      glucose, insulin and protein-bound sugars were higher and activities of enzymes
      of glucose metabolism were altered in HFD-fed rats, as compared to control
      animals. The levels were brought back to near-normal when administered with CBEt
      at high dose. CBEt also prevented the hyperlipidaemia observed in fructose-fed
      rats and improved glucose tolerance. CBEt did not show any significant effect in
      fructose-fed rats when administered at low dose. CONCLUSION: These findings
      indicate the improvement of glucose metabolism in-vivo by CBEt in fructose-fed
      rats.

PMID- 16990961
TI  - Leptin alters brain adenosine triphosphatase activity in ethanol-mediated
      neurotoxicity in mice.
AB  - INTRODUCTION: This study aimed to assess the leptin dependent changes on
      adenosine triphosphatase (ATPase) activities of the central nervous system during
      chronic ethanol supplementation. METHODS: The mice were divided into four groups.
      Group 1 consisted of control animals that received isocaloric glucose, Group 2
      animals received isocaloric glucose plus exogenous mouse recombinant leptin (230
      microgrammes/kilogramme body weight intraperitoneally) every alternate day, Group
      3 were alcohol-fed mice (6.32 grammes/kilogramme body weight orally), and Group 4
      were alcohol-fed mice that received leptin (230 microgrammes/kilogramme body
      weight intraperitoneally) every alternate day. The experiment was terminated
      after giving the mice leptin injections for 15 days. RESULTS: Ethanol feeding for
      a total period of 45 days (p-value is less than 0.05) significantly elevated the
      brain lipid hydroperoxide levels and total ATPases, sodium, potassium-ATPase and
      magnesium-ATPase activities but significantly decreased the calcium-ATPase
      activity. Leptin injections to ethanol-fed animals further elevated the levels of
      lipid hydroperoxides, total ATPases, sodium, potassium-ATPase and magnesium
      ATPase, while calcium-ATPase activity was reduced significantly. CONCLUSION:
      Leptin plays an important role in the pathogenesis of ethanol-induced
      neurotoxicity by enhancing brain lipid peroxidation and regulating brain ATPase
      activities in mice. Thus, hyperleptinaemia-induced oxidative stress and enhanced
      ATPase activities may be important pathogenic factors in brain toxicity.

PMID- 16990962
TI  - Menstruation among adolescent girls in Malaysia: a cross-sectional school survey.
AB  - INTRODUCTION: The onset of menstruation is part of the maturation process.
      However, variability in menstrual cycle characteristics and menstrual disorders
      are common. The purpose of this study was to determine the menstrual
      characteristics of adolescent females and factors associated with it. METHODS:
      This is a cross-sectional descriptive study carried out on 2,411 secondary school
      adolescent females in Negeri Sembilan, Malaysia. Data were collected using a self
      administered structured questionnaire on menstruation in Bahasa Malaysia.
      RESULTS: Abnormal cycle length (menstrual cycle longer than 35 days or cycle
      length between 14 to 20 days or irregular pattern) was common and affected 37.2
      percent of subjects. The majority (74.6 percent) experienced premenstrual
      syndrome and 69.4 percent had dysmenorrhoea. About 18 percent reported excessive
      menstrual loss (use two pads at a time to prevent blood from soaking through or
      confirmed by doctor to be anaemic due to heavy menstrual flow). Only 11.1 percent
      of schoolgirls seeked medical consultation for their menstrual disorders. Mothers
      remained the most important source of information (80 percent). Menstrual
      disorders were significantly more common in female adolescents who smoke and have
      suicidal behaviours (p-value is less than 0.05). CONCLUSION: Menstrual problems
      among adolescent female are common. They are influenced by certain modifiable
      factors.

PMID- 16990963
TI  - Sleep duration and its correlates in a sample of Saudi elementary school
      children.
AB  - INTRODUCTION: This study was conducted to estimate sleep duration in Saudi
      elementary school children, sleep habits and practices that may affect it, and
      compare our results to published data in other societies. METHODS: Parents of
      elementary school children were surveyed regarding their children's bedtime, rise
      time, sleep duration at night and daytime nap duration during weekdays and
      weekends. A questionnaire inquiring about demographical data, specific sleep
      problems and habits, and home environment was completed by the parents. RESULTS:
      The study comprised 511 (50.5 percent) boys and 501 (49.5 percent) girls. During
      weekdays, bedtime for the whole group was 21.3 +/- 1.8 hours, rise time was 5.9
      +/- 0.5 hours, total sleep time (TST) was 8.4 +/- 1.1 hours, and TST and nap was
      9.98 +/- 1.3 hours. Multivariate analysis revealed that TST was affected by
      regularity of bedtime, mother's level of education, daytime naps, and the habits
      of watching television (TV) and playing computer games after 20.00 hours.
      CONCLUSION: Nighttime sleep duration is shorter in Saudi school children compared
      to published data. Several factors appeared to affect sleep duration, including
      mother's educational level, daytime naps and watching TV at night.

PMID- 16990964
TI  - Assessing the quality of care for patients with first-episode psychosis.
AB  - INTRODUCTION: This study evaluated the quality of care in an early psychosis
      intervention programme (EPIP), as compared to standard treatment received by
      patients prior to the inception of the programme. METHODS: The medical records of
      50 patients with first-episode psychosis (FEP) who received psychiatric treatment
      in the calendar year of 2000, i.e. prior to the implementation of EPIP, and 87
      FEP patients who were accepted in the EPIP, were reviewed for a period of one
      year. These patients were aged between 18 and 40 years. Each medical record was
      reviewed for a list of process indicators, which were identified from the
      published literature and other treatment guidelines, and covered different
      domains. RESULTS: None of the pre-EPIP patients met all the 13 process
      indicators, whereas 48 percent of EPIP patients met all the indicators (p-value
      is less than 0.001). Using the default rate as a proxy of outcome, we found that
      19 percent of EPIP patients had defaulted at the end of one year, whereas the
      default rate was 52 percent for the pre-EPIP patients (p-value is less than
      0.001). CONCLUSION: It is possible to improve the quality of care in patients
      with FEP through the use of treatment guidelines, regular monitoring of symptoms
      and side effects, and periodic audits.

PMID- 16990965
TI  - An epidemiological and knowledge, attitudes, beliefs and practices study of
      sexually transmitted infections in older men.
AB  - INTRODUCTION: This study was conducted to determine the disease patterns of
      sexually transmitted infections (STI) in older men, as well as to gather
      information on their knowledge, attitudes, beliefs and sexual practices. METHODS:
      A prospective study was carried out from January to June 2005 in men aged 50
      years or older who attended the Department of STI Control clinic. RESULTS: There
      were 104 men enrolled. The majority (92.3 percent) were Chinese, and 62.5 percent
      were aged between 50 and 59 years, 25.9 percent between 60 and 69 years, and 11.5
      percent aged 70 years or older. The patients were predominantly heterosexual, and
      had fairly low levels of education--85.6 percent of the patients had received
      primary or secondary school level of education. Majority (79.8 percent) of the
      men had been sexually active in the preceding six months, and 37.3 percent had
      paid sex during that time. 29.8 percent of men reported having taken drugs such
      as sildenafil (Viagra, Pfizer, New York, NY, USA) or similar drugs such as
      vardenafil (Levitra, Bayer, Wuppertal, Germany) or tadalafil (Cialis, Eli Lilly,
      Indianapolis, IN, USA). 56.7 percent of the men had active infections, with non
      gonococcal urethritis (15.4 percent), genital warts (12.5 percent) and gonorrhoea
      (10.6 percent) being the commonest. Generally, condom usage was accepted as an
      effective way to prevent transmission of STI. However, many of the men surveyed
      felt that condom usage reduced their sexual pleasure, and 38.5 percent felt that
      condoms were inconvenient. There were also areas of human immunodeficiency virus
      (HIV) knowledge that were lacking. Most patients listed the media as their main
      source of knowledge about STI and HIV. CONCLUSION: Older males attending the
      clinic remain at significant risk of STI and targeted educational efforts are
      warranted.

PMID- 16990966
TI  - Comparison of the VBM laryngeal tube and laryngeal mask airway for ventilation
      during manual in-line neck stabilisation.
AB  - INTRODUCTION: The purpose of this study is to assess whether the newly-developed
      VBM (Medizintechnik GmbH, Sulz, Germany) laryngeal tube (LT) is able to provide
      adequate ventilation and oxygenation to patients with an unstable neck and
      require airway management. The haemodynamic responses to insertion between the
      two devices were also studied. We compared the LT to the laryngeal mask airway
      (LMA) as an alternative airway management tool in adult patients with unstable
      neck and who underwent intubation with manual in-line neck stabilisation.
      METHODS: A randomised single-blinded prospective study was conducted involving a
      total of 40 American Society of Anesthesiology I and II pre-medicated patients
      who were divided into two groups, LT or LMA, for airway management during
      elective surgery. There were 20 patients for each group. After pre-oxygenation,
      anaesthesia was induced using intravenous (i.v.) fentanyl and i.v. propofol. The
      neuromuscular blockade was produced with either i.v. vecuronium or i.v.
      atracurium. The LT or LMA was inserted after neuromuscular blockade was confirmed
      using a peripheral nerve stimulator (train-of-four 1). A size 3, 4 or 5 LT or a
      size 3 or 4 LMA was inserted while the patient's head and neck were being
      stabilised by an assistant who held the sides of the neck and the mastoid
      processes (manual in-line stabilisation). If it was not possible to ventilate the
      lungs, or if end-tidal carbon dioxide and/or chest movement did not indicate a
      patent airway, the LT or LMA was removed. After three failed attempts, the study
      was terminated and the airway was secured in the most suitable manner determined
      by the anaesthetist. After successful placement of LT or LMA, anaesthesia was
      maintained with 66 percent nitrous oxide in oxygen and 2 minimum alveolar
      concentration sevoflurane. All patients received standard anaesthesia monitoring.
      The ease of insertion, the number of attempts needed to successfully secure the
      airway, episodes of desaturation (less than 95 percent) and end-tidal carbon
      dioxide at various time intervals were studied. The haemodynamic parameters such
      as systolic blood pressure, diastolic blood pressure, mean arterial pressure and
      heart rate at different time intervals were also studied. RESULTS: The study
      showed a statistically significant difference in time required for successful
      insertion between the groups; time required for LT was 24.8 +/- 7.7 seconds and
      LMA was 36.1 +/- 17.3 seconds (p-value equals 0.01). Both groups had no
      statistical differences (p-value is greater than 0.05) in number of attempts
      needed to achieve a patent airway, and the successful insertion rate was 100
      percent for both groups. There were also no statistical differences in the
      haemodynamic response to insertion and the end-tidal carbon dioxide in this
      study. CONCLUSION: We conclude that, under anaesthesia, the LT was a valuable and
      better alternative to LMA for ventilation and airway management when the
      patient's head and neck are stabilised by the manual in-line method.

PMID- 16990967
TI  - Spontaneous rapid osteolysis in Paget's disease after internal fixation of
      subtrochanteric femoral fracture.
AB  - Rapidly-progressive spontaneous progression of the osteolysis following internal
      fixation of pathological fracture in patients with Paget's disease has not been
      previously reported. We describe two patients, aged 59 and 65 years,
      respectively, who had pathological subtrochanteric fractures in Pagetic femora
      fixed internally using an interlocked intramedullary nail, and who developed
      spontaneous rapid osteolysis. Both patients responded favourably to long-term
      treatment with alendronate, with resultant fracture union and resolution of
      osteolysis.

PMID- 16990968
TI  - Leiomyoma of the oesophagus managed by thoracoscopic enucleation.
AB  - The authors document two patients with oesophageal leiomyoma. In the first
      patient, a 41-year-old man, enucleation of the oesophageal leiomyoma was
      initially attempted by a thoracoscopic approach, but because of adherence of the
      tumour to the oesophageal mucosa, enucleation was completed by thoracotomy.
      Thoracoscopic enucleation was successfully performed in the second patient, a 62
      year-old man. This paper includes a literature review on the pathology, diagnosis
      and surgical approach in the management of oesophageal leiomyoma. In conclusion,
      prudent use of thoracoscopic approach in the enucleation of oesophageal leiomyoma
      could potentially result in shorter hospital stay, decreased postoperative pain
      and reduced requirement for postoperative analgesia.

PMID- 16990969
TI  - Dyspnoea due to plasma transfusion-related acute lung injury.
AB  - We describe an unusual case of unexpected dyspnoea following transfusion of fresh
      frozen plasma (FFP) in a previously-well 72-year-old woman. Our patient was
      scheduled for an ultrasonographically-guided liver biopsy for work-up for
      autoimmune hepatitis. She was given FFP to correct a prolonged prothrombin time.
      Shortly after the transfusion was initiated, she started coughing and became
      progressively dyspnoeic. Clinically, she was tachypnoeic with diffuse bilateral
      crepitations, and rapidly went into respiratory failure. She was intubated and
      placed on mechanical ventilation. Her condition improved and she was extubated by
      the second day, with no long-term pulmonary sequelae. A diagnosis of transfusion
      related acute lung injury (TRALI) was made, based on the rapidity of onset and
      association with transfusion. This was confirmed by the findings of anti-human
      leukocyte antigen antibodies in both the patient and recipient blood. Our case
      highlights this important but under-recognised condition. The incidence,
      diagnosis and management of TRALI are also discussed.

PMID- 16990970
TI  - Radiation-induced osteosarcoma of the maxilla.
AB  - Radiation-induced sarcomas are well-known though uncommon potential late sequelae
      of radiation therapy. We report irradiation-induced osteosarcoma involving the
      maxilla following treatment of nasopharyngeal carcinoma in a 44-year-old man who
      presented with painful cheek swelling. Radiographs and computed tomography showed
      a large destructive lesion of the left maxilla. Diagnosis of osteosarcoma was
      confirmed by excision biopsy.

PMID- 16990971
TI  - Pseudoaneurysm of inferior epigastric artery complicating ileostomy construction.
AB  - Pseudoaneurysm of the inferior epigastric artery complicating ileostomy
      construction is described in a 25-year-old woman. She underwent total abdominal
      perineal proctocolectomy with a permanent ileostomy constructed through the right
      rectus muscle. 15 days later, she abruptly developed significant bleeding through
      the ileostomy that recurred two more times. Endoscopy performed through the
      ileostomy stoma revealed a small ulcer 8 cm from the stomal opening. The distal
      segment of ileum containing the bleeding site was resected, and on-table
      examination of the lesion revealed an underlying tear in the inferior epigastric
      artery wall. The patient recovered after the operation.

PMID- 16990972
TI  - Electrocardiographical case. Acute severe chest tightness.
AB  - The early diagnosis of acute myocardial infarction is crucial for the institution
      of appropriate reperfusion therapy. We describe a 56-year-old man who developed
      sudden onset of severe chest tightness. Inferior, posterior and right ventricular
      ST elevation myocardial infarction was diagnosed on electrocardiography (ECG).
      The ECG interpretation, differential diagnosis and management are discussed.

PMID- 16990974
TI  - Tactile stimulation-induced rapid elevation of the synaptophysin mRNA expression
      level in rat somatosensory cortex.
AB  - Synaptophysin is an integral membrane protein abundant in the synaptic vesicle
      and is found in nerve terminals throughout the brain. It was recently suggested
      that synaptophysin is also involved in the modulation of activity-dependent
      synapse formation. In this study, we examined at the individual level whether
      tactile stimulation selectively influenced the synaptophysin mRNA expression
      level in the somatosensory cortex of rats. Anesthetized rats were caressed on the
      back by an experimenter's palms for 20 min and the mRNA expression levels in the
      somatosensory and the visual cortices 5 min afterwards were determined using
      quantitative PCR methodology. The synaptophysin mRNA expression level was
      selectively higher in the experimental group than in the control group in the
      somatosensory cortex but not in the visual cortex. This suggests that the mRNA
      expression level of synaptophysin induced by neuronal activity is related to the
      regulation of synapse formation or remodeling or both.

PMID- 16990975
TI  - Combined measurement of hepatocyte growth factor and carcinoembryonic antigen as
      a prognostic marker for patients with dukes a and B colorectal cancer: results of
      a five-year study.
AB  - PURPOSE: There is no marker capable of differentiating patients with Dukes A and
      B colorectal cancer with aggressive diseases from those with indolent diseases.
      We evaluated the results of five years of actuarial survival data to determine
      whether serial monitoring of serum hepatocyte growth factor could provide
      prognostic information on these patients. METHODS: Blood samples of 147
      colorectal cancer patients were obtained and the serum concentration of
      hepatocyte growth factor was measured. RESULTS: Elevated serum hepatocyte growth
      factor levels were associated with stage progression. Although the overall
      positive rate of hepatocyte growth factor in the patients was the same as that of
      the carcinoembryonic antigen, the positive rate of hepatocyte growth factor in
      the Dukes A patients was two times higher than that of the carcinoembryonic
      antigen, and nearly 40 percent of the carcinoembryonic antigen-negative patients
      had a positive serum hepatocyte growth factor in the Dukes A and B
      classification. In this subgroup, patients with positive serum hepatocyte growth
      factor or carcinoembryonic antigen levels had a poorer prognosis, whereas
      positive serum hepatocyte growth factor level after surgery could predict disease
      recurrence. CONCLUSIONS: A combination of serum hepatocyte growth factor and
      carcinoembryonic antigen tests might be useful for selecting patients with
      aggressive diseases in Dukes A and B classification.

PMID- 16990976
TI  - Botulinum toxin vs. topical glyceryl trinitrate ointment for pain control in
      patients undergoing hemorrhoidectomy: a randomized trial.
AB  - PURPOSE: The maximum resting pressure in the anal canal is greatly raised after
      hemorrhoidectomy. This increase is likely to be the cause of postoperative pain,
      which is still the most troublesome early problem after hemorrhoidectomy. This
      study was designed to compare, after hemorrhoidectomy, the effects of
      intrasphincter injection of botulinum toxin vs. application of glyceryl
      trinitrate ointment in improving wound healing and reducing postoperative pain at
      rest or during defecation. METHODS: Thirty patients with hemorrhoids of third and
      fourth degree were included in the study and randomized in two groups. Anorectal
      manometry was performed preoperatively and 5 and 40 days after hemorrhoidectomy.
      One group received one injection containing 20 IU of botulinum toxin, whereas the
      other an application of 300 mg of 0.2 percent glyceryl trinitrate ointment three
      times daily for 30 days. RESULTS: Five days after hemorrhoidectomy, maximum
      resting pressure was significantly reduced compared with baseline values in both
      groups (85 +/- 15 vs. 68 +/- 11 mmHg for the group treated with botulinum toxin,
      87 +/- 11 vs. 78 +/- 11 mmHg for the group treated with glyceryl trinitrate
      ointment). Overall analysis of postoperative pain at rest showed a significant
      reduction in the botulinum toxin group vs. glyceryl trinitrate group, whereas
      pain during defecation and time of healing were similar. Adverse effects, such as
      headaches, were observed only in the glyceryl trinitrate group. Forty days after
      hemorrhoidectomy in the glyceryl trinitrate group, maximum resting pressure
      values were similar to preoperative ones, whereas the values were still reduced
      in the botulinum toxin group. CONCLUSIONS: A single intrasphincter injection of
      botulinum toxin was more effective and safer than repeated applications of
      glyceryl trinitrate in reducing early postoperative pain at rest but not during
      defecation.

PMID- 16990977
TI  - Sinus excision for the treatment of limited chronic pilonidal disease: results
      after a medium-term follow-up.
AB  - PURPOSE: We have previously introduced a minimally invasive technique for the
      treatment of limited pilonidal disease. In this paper, the results for patients
      who had at least one year of follow-up are provided. METHODS: All patients
      operated with the sinus excision technique were studied retrospectively and those
      who had a follow-up period shorter than 12 months were excluded. Demographics,
      perioperative and postoperative data, and patient satisfaction scores were
      obtained from a prospectively designed database. Limited pilonidal disease was
      defined as disease presenting with less than four visible pits. RESULTS: Sixty
      two patients (56 males, 90.3 percent; mean age, 25.8 +/- 10.4 years) were
      included in the study. Patients returned to work in 1.9 +/- 0.7 days, and the
      mean healing period was 43 +/- 10.4 days. All procedures were performed under
      local anesthesia, and the mean operation time was 9.7 +/- 3.4 minutes. The number
      of outpatient procedures was 45 (72.6 percent). One patient suffered from a minor
      complication (bleeding that was stopped with electrocauterization; n = 1, 1.6
      percent) and recurrence was observed in another case (n = 1, 1.6 percent).
      Patients received a satisfaction questionnaire, which revealed that 34 patients
      (54.8 percent) were "completely satisfied with the procedure" and 49 (79 percent)
      would "absolutely recommend the technique to other patients." CONCLUSIONS: Sinus
      excision is an advisable technique for the treatment of limited pilonidal
      disease, because it can be performed under local anesthesia mostly as an
      outpatient procedure and the operation time is extremely short. Although the
      healing period is long, the off-work period is short, and patients are generally
      satisfied with the procedure. After a medium-term follow-up, the complication and
      recurrence rates are acceptable. We believe that sinus excision technique is a
      simple and effective method for the treatment of limited pilonidal disease.

PMID- 16990978
TI  - Adult intussusception: a retrospective review.
AB  - PURPOSE: Whereas intussusception is relatively common in children, it is
      clinically rare in adults. The condition is usually secondary to a definable
      lesion. This study was designed to review adult intussusception, including
      presentation, diagnosis, and optimal treatment. METHODS: A retrospective review
      of 22 cases of intussusception occurring in individuals older than aged 18 years
      encountered at two university-affiliated hospitals in Winnipeg between 1989 and
      2000. The 22 cases were divided to benign and malignant enteric, ileocolic,
      colonic lesions respectively. The diagnosis and treatment of each case were
      reviewed. RESULTS: There were 22 cases of adult intussusception. Mean age was
      57.1 years. Abdominal pain, nausea, and vomiting were the commonest symptoms.
      There were 14 enteric, 2 ileocolic, and 6 colonic intussusceptions. Eighty-six
      percent of adult intussusception was associated with a definable lesion. Twenty
      nine percent of enteric lesions were malignant. All ileocolic lesions were
      malignant. Of colonic lesions, 33 percent were malignant and 67 percent were
      benign. All cases required surgical interventions except one. CONCLUSIONS: Adult
      intussusception is a rare entity and requires a high index of suspicion. Our
      review supports that small-bowel intussusception should be reduced before
      resection if the underlying etiology is suspected to be benign or if the
      resection required without reduction is deemed to be massive. Large bowel should
      generally be resected without reduction because pathology is mostly malignant.

PMID- 16990979
TI  - Clinical and subclinical leaks after low colorectal anastomosis: a clinical and
      radiologic study.
AB  - PURPOSE: This study was designed to examine the natural history of subclinical
      leaks and their effect on bowel function and quality of life and to evaluate
      water-soluble contrast enema features that predict anastomotic healing after
      leaks. METHODS: Consecutive patients who underwent low rectal anastomosis were
      followed up postoperatively for leaks. All leaks were confirmed radiologically
      with CT scanning and water-soluble contrast enema imaging. Water-soluble contrast
      enemas were serially repeated to identify healing. Characteristics on initial
      water-soluble contrast enema were correlated with observed healing.
      Postoperatively, patients were required to fill in a quality of life and a bowel
      function questionnaire. RESULTS: A total of 138 patients underwent low rectal
      anastomosis procedures with a median follow-up period of 26 (interquartile range,
      19-37) months. There were 23 documented leaks of which 13 (9 percent) presented
      clinically and 10 (8 percent) presented subclinically. Ileostomy closure was
      possible in 4 of 13 (30 percent) patients with a clinical leak and all 10 (100
      percent) patients with a subclinical leak. Median quality of life scores were
      lower for patients with clinical leaks and no ileostomy closure (P = 0.03). Bowel
      function for subclinical leak patients and clinical leak patients with ileostomy
      closure were similarly impaired. The presence of a cavity (P = 0.01) and a
      stricture (P = 0.01) at the anastomotic site were unfavorable radiologic features
      associated with nonhealing. CONCLUSIONS: Subclinical leaks are more benign in
      their natural history compared with clinical leaks. Quality of life and bowel
      function is no better in patients with a subclinical leak compared with patients
      with a clinical leak who have ileostomy closure. Anastomotic leaks may resolve if
      favorable radiologic features are present.

PMID- 16990980
TI  - The importance of colonoscopy in colorectal surgeons' practices: results of a
      survey.
AB  - PURPOSE: The role of colonoscopy in the prevention of colorectal cancer has been
      accepted, not only by the medical community but by the federal government as
      well. This study sought to document the current role of colonoscopy in the
      practices of colorectal surgeons. METHODS: A survey was mailed to members of The
      American Society of Colon and Rectal Surgeons detailing the scope of colonoscopy
      in their practices. RESULTS: Surveys were mailed to 1,800 members of The American
      Society of Colon and Rectal Surgeons; responses were received from 778 (43.2
      percent). The mean age was 48 +/- 10 (range, 27-79) years; the mean number of
      years in practice was 14 +/- 10 (range, 0.2-48). The majority of respondents (91
      percent) were male. Responses were received from 47 U.S. states and 30 foreign
      countries. Seventy-four respondents (9.5 percent) reported not performing
      colonoscopy; the most common reason cited was "referring physicians' preference"
      (45 percent). Seven-hundred four respondents (90.5 percent) reported performing
      colonoscopy as part of their clinical practice and reported an average of 41 +/-
      41 colonoscopies in the last month (range, 0-635) and 457 +/- 486 in the last
      year (range, 2-7,000). Colonoscopy accounted for 23 +/- 16 percent of responding
      physicians' clinical time (range, 1-100 percent) and 27 +/- 19 percent of total
      charges (range, 0-100 percent). Nearly all respondents (97 percent) anticipated
      maintaining or increasing their volume of colonoscopy in the coming year. Eighty
      four percent of respondents reported receiving some or all of their training in
      colonoscopy during a colon and rectal surgery fellowship. More than one-half of
      respondents (55 percent) believed that there should be more of an emphasis on
      colonoscopy on the American Board of Colon and Rectal Surgery board examination,
      and 81 percent believed that the annual meeting of The American Society of Colon
      and Rectal Surgeons should include lectures and/or courses covering colonoscopy.
      CONCLUSIONS: Colonoscopy plays a major role in the practices of colorectal
      surgeons across the world, accounting for approximately one-quarter of clinical
      time and total charges. Based on the expectation that this trend will continue,
      The American Society of Colon and Rectal Surgeons needs to aggressively support
      its members not only in the technical aspects of colonoscopy but also in the
      practice management issues.

PMID- 16990981
TI  - Sustainable water quality management framework and a strategy planning system for
      a river basin.
AB  - In Taiwan, the authorities have spent years working on remedying polluted rivers.
      Generally, the remediation planning works are divided into two phases. During the
      first phase, the allowed pollution discharge quantity and abatement quantity of
      each drainage zone, including the assimilative capacity, are generated based on
      the total river basin. In the second phase, the abatement action plans for each
      pollution source in each drainage zone are respectively devised by the related
      organizations based on the strategies generated during the first phase. However,
      the effectiveness of linking the two phases is usually poor. Highly integrated
      performances are not always achieved because the separate two-phase method does
      not take system and management thinking into consideration in the planning stage.
      This study pioneers the use of the Managing for Results (MFR) method in planning
      strategies and action plans for river water quality management. A sustainable
      management framework is proposed based on the concept and method of MFR,
      Management Thinking, and System Analysis. The framework, consisting of planning,
      implementation, and controlling stages, systematically considers the
      relationships and interactions among four factors: environment, society, economy,
      and institution, based on the principles of sustainable development. Based on the
      framework, the Modified Bounded Implicit Enumeration algorithm, which is used as
      a solving method, is combined with Visual Basic software and MS Excel to develop
      a computer system for strategy planning. The Shetzu River, located in northern
      Taiwan, is applied as a case study. According to the theoretical, practical, and
      regulatory considerations, the result-oriented objectives are defined to first
      improve the pollution length of the Shetzu River in specific remediation periods
      to finally meet regulated water quality standards. The objectives are then
      addressed as some of the constraints for the strategy planning model. The model
      objective is to pursue the maximum assimilative capacity (environmental phase)
      subjected to the constraints of water quality standards (institutional phase),
      social equity (social phase), and proper available technology (economic phase).
      The pollution quantity abatement and allocation, which are named the top
      strategies, of each drainage zone for different scenarios can be obtained based
      on each water quality standard. The middle as well as lower strategies and action
      plans, which consist of pollution quantity abatement and allocation of each class
      (domestic, industrial, livestock, and non-point pollution sources) and their
      individual pollution sources in each drainage zone, are then generated based on
      the top strategies. The performance indicators and measure plans are proposed
      based on the action plans to promote the comprehensive effectiveness of river
      water quality management. The authorities have begun to develop a budget based on
      the strategies and action plans developed in this study. The analytical results
      indicate that the objectives, strategies, and action plans developed based on the
      sustainable management framework and strategy planning system can effectively
      help the related authorities to fulfill the tasks of water quality management for
      a river basin.

PMID- 16990982
TI  - BR-319: Brazil's Manaus-Porto Velho highway and the potential impact of linking
      the arc of deforestation to central amazonia.
AB  - Brazil's BR-319 Highway linked Manaus, in the state of Amazonas, to Porto Velho,
      Rondonia, until it became impassable in 1988. Now it is proposed for
      reconstruction and paving, which would facilitate migration from the "Arc of
      Deforestation" in the southern part of the Amazon region to new frontiers farther
      north. The purpose of the highway, which is to facilitate transport to Sao Paulo
      of products from factories in the Manaus Free Trade Zone, would be better served
      by sending the containers by ship to the port of Santos. The lack of a land
      connection to Manaus currently represents a significant barrier to migration to
      central and northern Amazonia. Discourse regarding the highway systematically
      overestimates the highway's benefits and underestimates its impacts. A variety of
      changes would be needed prior to paving the highway if these potential impacts
      are to be attenuated. These include zoning, reserve creation, and increased
      governance in various forms, including deforestation licensing and control
      programs. More fundamental changes are also needed, especially the abandonment of
      the long-standing tradition in Brazil of granting squatters' rights to those who
      invade public land. Organizing Amazonian occupation in such a way that road
      construction and improvement cease to lead to explosive and uncontrolled
      deforestation should be a prerequisite for approval of the BR-319 and other road
      projects for which major impacts are expected. These projects could provide the
      impetus that is needed to achieve the transition away from appropriation of
      public land by both small squatters and by grileiros (large-scale illegal
      claimants). A delay in reconstructing the highway is advisable until appropriate
      changes can be effected.

PMID- 16990983
TI  - Effects of physical habitat degradation on the stream fish assemblage structure
      in a pasture region.
AB  - We compared the fish assemblage structure from streams with different intensities
      of physical habitat degradation and chemical water pollution by domestic sewage
      in southeastern Brazil. Eight streams (R1-R8) showing less disturbed or more
      disturbed conditions of chemical water quality and of physical habitat quality
      were selected. Cumulative abundance and biomass, combined in ABC plots, revealed
      (i) biomass curves above the abundance curves, represented by the streams R1-R2
      (water and habitat less disturbed) and R5-R6 (water more disturbed and habitat
      less disturbed), and (ii) biomass curves below the abundance curves, represented
      by the streams R3-R4 (water less disturbed and habitat more disturbed) and R7-R8
      (water and habitat more disturbed). The quantitative structure of the
      ichthyofauna showed significant correspondence with physical habitat condition
      but not with chemical water quality. The most significant species to cause the
      dissimilarity between less disturbed and more disturbed physical habitats was the
      exotic Poecilia reticulata. Such results indicate that in the focused region-with
      little influence of industrial pollution, noncritical domestic sewage discharge,
      and soil predominantly used for pasture-streams with high physical habitat
      integrity possess a differently structured ichthyofauna than streams with
      relatively low physical habitat integrity, reinforcing the importance of the
      physical habitat quality and riparian conservation along these water courses,
      warranting the conservation of these systems. Indeed, our results also reinforce
      the importance of including biotic descriptors, particularly of the ichthyo
      fauna, in water-monitoring programs designed to reveal signs of human
      interference.

PMID- 16990984
TI  - Definition of homogeneous environmental management units for the Catalan coast.
AB  - Geographical areas constitute the basic implementation locus for integrated
      coastal zone management strategies and activities. Because the definition of
      territorial planning objectives may be affected by socioeconomic and
      environmental characteristics, one of the main steps in the process involves
      dividing the coast into homogeneous environmental management units (HEMUs). This
      article presents a general and simple method for regionalizing the landside of a
      coastal zone into HEMUs and illustrates it through application to the Catalan
      coast. Socioeconomic and natural (biophysical) subsystems were selected as the
      most appropriate dimensions of the regionalization process. Dimensions were
      described using 11 spatial themes, which were managed in a geographic information
      system environment that proved to be an adequate tool for the purpose. A final
      coastal zone map of four classes of HEMUs connected to local administrative units
      was obtained, and because it reflects the current natural and socioeconomic
      dynamics, it can be considered as an initial step in the planning process for the
      Catalan coast. Although the proposed method was developed based on the
      characteristics of the Catalan coast, it is general enough to be adapted and
      applied to most developed or developing coastal areas.

PMID- 16990985
TI  - Using a state-and-transition approach to manage endangered Eucalyptus albens
      (White Box) woodlands.
AB  - Eucalyptus albens (White Box) woodlands are among the most poorly conserved and
      threatened communities in Australia. Remnants are under further threat from stock
      grazing, deteriorating soil conditions, weed invasion, and salinity. There is an
      urgent need to restore degraded White Box and other woodland ecosystems to
      improve landscape function. However, there is still a poor understanding of the
      ecology of degraded woodland ecosystems in fragmented agricultural landscapes,
      and consequently a lack of precise scientific guidelines to manage these
      ecosystems in a conservation context. State and Transition Models (STMs) have
      received a great deal of attention, mainly in rangeland applications, as a
      suitable framework for understanding the ecology of complex ecosystems and to
      guide management. We have developed a STM for endangered White Box woodlands and
      discuss the merits of using this approach for land managers of other endangered
      ecosystems. An STM approach provides a greater understanding of the range of
      states, transitions, and thresholds possible in an ecosystem, and provides a
      summary of processes driving the system. Importantly, our proposed STM could be
      used to clarify the level of "intactness" of degraded White Box woodland sites,
      and provide the impetus to manage different states in complementary ways, rather
      than attempting to restore ecosystems to one pristine stable state. We suggest
      that this approach has considerable potential to integrate researcher and land
      manager knowledge, focus future experimental studies, and ultimately serve as a
      decision support tool in setting realistic and achievable conservation and
      restoration goals.

PMID- 16990986
TI  - Assessing the institutional effectiveness of state environmental agencies in
      Turkey.
AB  - Improving the performance of the state environmental agencies (SEAs) necessitates
      an effective institutionalization of governmental environmental management
      functions. There are examples of successful and unsuccessful SEAs in several
      parts of the world. Analysis and assessment of these cases can deliver useful
      insights for institution builders. The objective of this article is the
      assessment of the institutional effectiveness of the SEAs in Turkey through the
      perceptions of the experts using the Delphi Technique. In this regard, a
      checklist is developed including 16 criteria and 123 subcriteria to measure the
      institutional effectiveness of the SEAs. Twenty-eight national and international
      experts have formed a Delphi panel and evaluated the national and local
      conditions. Results, based on the perceptions of the experts, indicate that the
      overall effectiveness of the SEAs is far less than satisfactory. Negative
      consensus has been reached over the effectiveness of 13 of the 16 criteria and 95
      of the 123 subcriteria; however, no consensus has been achieved over the
      remainder of the parameters. The survey has also proven that the Delphi Technique
      can be effectively used for that purpose. Utilization of the checklist method is
      also useful in diagnosing the problematic components of the SEAs. It is
      recommended that this approach be used in similar cases elsewhere.

PMID- 16990987
TI  - ASCO/SSO review of current role of risk-reducing surgery in common hereditary
      cancer syndromes.
AB  - BACKGROUND: A significant portion of cancers are accounted for by a heritable
      component, which has increasingly been linked to mutations in specific genes.
      Clinical interventions have been formulated for mutation carriers within affected
      families. The primary interventions for mutation carriers of highly penetrant
      syndromes are surgical. METHODS: The American Society of Clinical Oncology and
      the Society of Surgical Oncology formed a task force charged with presenting an
      educational symposium on surgical management of hereditary cancer syndromes at
      annual society meetings, and this resulted in a position paper on this topic. The
      content of both the symposium and the position paper was developed as a consensus
      statement. RESULTS: This article addresses hereditary breast, colorectal,
      ovarian/endometrial, and multiple endocrine neoplasias. A brief introduction on
      the genetics and natural history of each disease is provided, followed by
      detailed descriptions of modern surgical approaches, clinical and genetic
      indications, timing of prophylactic surgery, and the efficacy of surgery (when
      known). Although several recent reviews have addressed the role of genetic
      testing for cancer susceptibility, this article focuses on the issues surrounding
      surgical technique, timing, and indications for surgical prophylaxis.
      CONCLUSIONS: Risk-reducing surgical treatment of hereditary cancer is a complex
      undertaking. It requires a clear understanding of the natural history of the
      disease, realistic appreciation of the potential benefits and risks of these
      procedures in potentially otherwise healthy individuals, and the long-term
      sequelae of such interventions, as well as the individual patient's and family's
      perceptions of surgical risk and anticipated benefit.

PMID- 16990988
TI  - Cervical spine metastasis from adrenal pheochromocytoma.
AB  - Metastatic tumours are the most common type of tumours in the spine of which only
      10% occur in the cervical spine. We report a rare presentation of metastatic
      pheochromocytoma of the cervical spine which was successfully treated
      operatively. Adequate precautions should be taken during surgery as the tumour is
      very vascular. Radiotherapy is useful in the treatment of residual tumour.

PMID- 16990989
TI  - Embolization of wide-necked aneurysms with using three or more microcatheters.
AB  - BACKGROUND: A new and relatively simple endovascular technique, in which more
      than three microcatheters are used for endovascular treatment of cerebral
      aneurysms for the first time, is described. METHOD: Eight patients with wide
      necked aneurysms were successfully treated with detachable coils using the
      multiple microcatheter technique. Three patients presented with subarachnoid
      haemorrhage and five were unruptured. The aneurysm locations were superior
      hypophyseal artery (2), posterior communicating artery (2), middle cerebral
      artery bifurcation (1), distal anterior cerebral artery (1), basilar artery (1)
      and vertebral artery (1). The average neck size was 7.4 +/- 2.8 mm (3.5-12 mm),
      average width of the aneurysms was 10.6 +/- 5.7 mm (6.2-23 mm) and depth was 8.9
      +/- 5.8 mm (3-22 mm). Three microcatheters (7 patients) and four microcatheters
      (1 patient) were introduced and used for coil delivery. Three or four coils were
      deployed and intermingled to stabilize the whole coil mass as well as to occupy
      the aneurysmal sac. When a relatively stable coil frame was formed, one coil was
      detached and subsequent coils were inserted. After the coil mass became more
      stable, other coils were also detached and all microcatheters were used for
      subsequent coil deployment. FINDINGS: All aneurysms were successfully treated
      without complications. Postemboilzation angiograms showed no contrast filling in
      5 cases (100% occlusion) and a very small residual neck in 3 cases. There was no
      procedure related complication. CONCLUSION: The multiple microcatheter technique
      can be one technical option for the endovascular treatment of wide necked
      aneurysms.

PMID- 16990990
TI  - Surgical resection of tumors located in subcortex of language area.
AB  - OBJECT: Although functional mapping facilitates the planning of surgery in and
      around eloquent areas, the resection of tumors adjacent to language areas remains
      challenging. In this report, we took notice that the language areas (Broca's and
      Wernicke's) present at the perisylvian fissure. We posit that if there is non
      essential language area on the inner surface of the Sylvian fissure, safe tumor
      resection may be possible even if the tumor is located under the language cortex.
      METHODS: The study population consisted of 5 patients with intrinsic brain tumors
      (frontal glioma, n = 3; temporal cavernous angioma, n = 1; primary malignant
      central nervous system lymphoma, n = 1) located in the perisylvian subcortex, in
      the language-dominant hemisphere. All patients underwent awake surgery and we
      performed intra-operative bipolar cortical functional language mapping. When the
      tumor was located under the language area, the Sylvian fissure was opened and the
      inner surface of the opercular cortex was exposed with the patient asleep, and
      additional functional mapping of that cortex was performed. This enabled us to
      remove the tumor from the non-functioning cortex. In our series, 4 of 5 patients
      had not language function on the inner surface of the operculum. Only one
      patient, a 52-year-old man with frontal glioblastoma (Case 3) had language
      function on the inner surface of the frontal operculum. CONCLUSION: We suggest
      that even perisylvian tumors located in the subcortex of the language area may be
      resectable via the nonfunctioning intrasylvian cortex by a transopercular
      approach without resultant language dysfunction.

PMID- 16990991
TI  - Activation of mitogenic pathways and sensitization to estrogen-induced apoptosis:
      two independent characteristics of tamoxifen-resistant breast cancer cells?
AB  - Paradoxical induction of apoptosis by estrogen has been described previously for
      estrogen-deprived and antiestrogen-resistant breast cancer cells. In this study
      we analyzed the possible interrelations between cell sensitization to estrogen
      apoptotic action and cell ability to (anti)estrogen-independent growth. Using
      tamoxifen-resistant sublines derived from the parent MCF-7 breast cancer cells by
      long-term tamoxifen treatment we demonstrated that resistant cells are
      characterized by increased level of EGF receptor and unexpected increase of VEGF
      receptor 2 (Flk-1/KDR) and its specific ligand, VEGF-A. The importance of the
      VEGF signaling in the autocrine regulation of cell growth was indicated by the
      ability of VEGF inhibitor, soluble fragment of Flt-1/Fc chimera, to suppress the
      phosphorylation of MAP kinases as well as to inhibit the estrogen-independent
      growth of MCF-7 cells. Sensitization of tamoxifen-resistant cells to estrogen
      induced apoptosis required the additional continuous cultivation in steroid
      depleted medium and did not depend on the activity of both EGF and VEGF pathways.
      Finally, we showed that treatment of the cells with 17beta-estradiol (10(-9) M)
      resulted in a marked increase in p53 level both in the resistant cells undergoing
      apoptosis and in the parent MCF-7 cells insensitive to apoptotic estrogen action.
      These data provide an important support for the existence of a disbalance between
      pro- and anti-apoptotic machinery in the resistant breast cancer cells that forms
      independently of the acquired ability to estrogen-independent growth.

PMID- 16990992
TI  - Phase I safety, tolerability, and pharmacokinetic study of recombinant human
      mannan-binding lectin.
AB  - Mannan-binding lectin (MBL), a human plasma protein, plays an important role in
      the innate immune defence. MBL recognizes microorganisms through surface
      carbohydrate structures. Due to genetic polymorphisms, MBL plasma concentrations
      range from 5 to 10,000 ng/mL. Approximately 30% of the human population have low
      levels of MBL (below 500 ng/mL). MBL deficiency is associated with increased
      susceptibility to infections in immunosuppressed individuals, e.g., during
      chemotherapeutically induced neutropenia. Replacement therapy with MBL may be
      beneficial in this patient group, and recombinant human MBL (rhMBL) is in
      development as a novel therapeutic approach. To assess the safety, tolerability,
      and pharmacokinetics of rhMBL, a placebo-controlled double-blinded study was
      performed in MBL-deficient healthy male subjects. rhMBL was administered as both
      single intravenous (i.v.) infusions (0.01, 0.05, 0.1, and 0.5 mg/kg) and repeated
      i.v. infusions (0.1 or 0.3 mg/kg given at 3-day intervals). There were no
      difference in incidence and type of adverse events reported in the study between
      the groups of subjects receiving rhMBL and the placebo group. All adverse events
      reported as drug-related were mild and no serious adverse events were recorded.
      There were no clinically significant changes in laboratory evaluations, ECG or
      vital signs, and no anti-MBL antibodies were detected following rhMBL
      administration. After single i.v. doses of rhMBL the maximal plasma levels
      increased in a dose-dependent manner reaching a geometric mean of 9710 ng/mL+/
      10.5% in the highest dose group (0.5 mg/kg), with an elimination half-life of
      approximately 30 h. No rhMBL accumulation in plasma was observed following repeat
      dosing. Administration of rhMBL restored the ability to activate the MBL pathway
      of the complement system without non-specific activation of the complement
      cascade. In conclusion, no safety or tolerability concern was raised following
      rhMBL administration no signs of immunogenicity detected, and an rhMBL plasma
      level judged sufficient to achieve therapeutic benefit (>1000 ng/mL) can be
      achieved.

PMID- 16990993
TI  - Transcranial sonography of the third ventricle and cognitive dysfunction in HIV
      patients.
AB  - BACKGROUND: Although the incidence and prevalence of dementia associated with
      human immunodeficiency virus (HIV) infection has decreased since the introduction
      of highly active antiretroviral therapy, cognitive dysfunction remains one of the
      most prevalent factors severely affecting quality of life in patients with HIV.
      Previous magnetic resonance imaging (MRI) studies showed a correlation between
      brain atrophy, enlargement of the ventricles and cognitive impairment in HIV
      patients. OBJECTIVE: To investigate the usefulness of transcranial sonographic
      (TCS) measurement of the third ventricle in detection of brain atrophy in HIV
      patients and the correlation with neuropsychological deficits. METHODS: We
      examined 47 HIV patients and 40 healthy age-matched controls with TCS,
      neuroimaging (cranial MRI or computed tomography) and a neuropsychological test
      battery. RESULTS: The third ventricle was significantly larger in patients than
      in healthy controls and correlated significantly with duration of HIV, Center of
      Disease Control (CDC) stage, CD4 lymphocytes and distinct cognitive and motor
      deficits. CONCLUSION: TCS cannot replace neuroimaging but is a valuable method in
      the detection of brain atrophy and follow-up of HIV patients at risk or with a
      recent diagnosis of HIV encephalopathy.

PMID- 16990994
TI  - Sequential maintenance treatment with glatiramer acetate after mitoxantrone is
      safe and can limit exposure to immunosuppression in very active, relapsing
      remitting multiple sclerosis.
AB  - Mitoxantrone has been approved by the FDA for worsening relapsing remitting and
      secondary progressive Multiple Sclerosis. However the benefits of this agent in
      reducing disease progression and relapse rate cannot be sustained in the long
      term, as treatment is limited by the potential for cumulative cardiotoxicity. We
      report our experience utilising Glatiramer Acetate as maintenance immuno
      modulatory treatment following initial immunosuppression with Mitoxantrone in a
      consecutive series of 27 patients with very active relapsing remitting disease,
      eight of whom had experienced continuing relapse activity on first-line
      treatment. Duration of treatment with Mitoxantrone and thereby cumulative dose
      were reduced as our experience with the combination increased.No unanticipated
      side effects of combination treatment were encountered over a follow-up period of
      66 months. A single patient developed therapy related acute leukaemia (TRAL) 9
      months after completion of Mitoxantrone.A sustained 90% reduction in annualised
      relapse rate (p < 0.001) has been observed. Disability is stable or improved in
      all patients a mean of 36 (16-66) months from initiation of treatment. Early
      suppression of relapse activity with Mitoxantrone has been maintained at a mean
      of 22 months from last dose of this agent. Only two relapses have occurred in the
      cohort since withdrawal of Mitoxantrone, occurring in the two patients who had
      previously been treated with Glatiramer Acetate. In 9 of the first 10 patients
      treated, imaged a mean of 27 months after withdrawal of Mitoxantrone, no
      enhancing lesions were identified on MRI brain scans. Glatiramer Acetate appears
      a safe and effective option for continuing disease modification in patients with
      relapsing remitting multiple sclerosis treated with Mitoxantrone. The treatment
      protocol utilised in later patients in this series appears to have the potential
      to limit exposure to this agent.

PMID- 16990995
TI  - Leptomeningeal familial amyloidosis: A rare differential diagnosis of
      leptomeningeal enhancement in MRI.

PMID- 16990996
TI  - Sir Thomas Lewis MD, FRS. (1881-1945).

PMID- 16990997
TI  - The phylogenetic analysis of hepatitis C virus isolates obtained from two Iranian
      carriers revealed evidence for a new subtype of HCV genotype 3.
AB  - Classification of hepatitis C virus is based on phylogenetic analysis of the
      strains reported world wide. Different strains are classified within 6 major
      genotypes and several minor groups (subtypes). In addition to epidemiologic value
      of determining genotype/subtype of this virus, the result may change the
      therapeutic strategy used for a patient. During a survey on hepatitis C in Iran,
      we found two cases assigned as 1b genotype by PCR-RFLP on 5' UTR, but three based
      on core region sequencing. Fragments from 5' UTR, Core and NS5b regions were PCR
      amplified and sequenced followed by phylogenetic analysis. Although the 5' UTR of
      this new strain is very similar to genotypes 1 and 6, analysis of core region
      classifies it in a separate branch of genotype 3, close to subtypes h and k.
      Further analysis of NS5b region put this new strain in a separate branch near
      other subtypes of genotype 3 and 4. These data are suggestive of a new subtype
      within genotype 3.

PMID- 16990998
TI  - Molecular characterization of a new begomovirus infecting Sida cordifolia and its
      associated satellite DNA molecules.
AB  - Two virus isolates Hn57 and Hn60 were obtained from Sida cordifolia showing mild
      upward leaf-curling symptoms in Hainan province of China. Comparison of partial
      sequences of DNA-A like molecule confirmed the existence of a single type of
      begomovirus. The complete nucleotide sequence of DNA-A of Hn57 was determined to
      be 2757 nucleotides, with a genomic organization typical of begomoviruses.
      Complete sequence comparison with other reported begomoviruses revealed that Hn57
      DNA-A has the highest sequence identity (71.0%) with that of Tobacco leaf curl
      Yunnan virus. Consequently, Hn57 was considered to be a new begomovirus species,
      for which the name Sida leaf curl virus (SiLCV) is proposed. In addition to DNA-A
      molecule, two additional circular single-stranded satellite DNA molecules
      corresponding to DNAbeta and DNA1 were found to be associated with SiLCV
      isolates. Both DNAbeta and DNA1 were approximately half the size of their cognate
      genomic DNA. Sequence analysis shows that DNAbeta of Hn57 and Hn60 share 93.8%
      nucleotide sequence identity, and they have the highest sequence identity (58.5%)
      with DNAbeta associated with Ageratum leaf curl disease (AJ316027). The
      nucleotide sequence identity between DNA1 of Hn57 and that of Hn60 was 83.8%,
      they share 58.2-79.3% nucleotide sequence identities in comparison with other
      previously reported DNAl.

PMID- 16990999
TI  - Construction of a multiprobe for the simultaneous detection of viroids infecting
      citrus trees.
AB  - Infections with different viroid species are common among cultivated fruit trees
      and grapevines, and many old-clone citrus varieties contain up to five citrus
      viroids (CVds) within a single tree. This paper describes the construction of a
      CVd-Multiprobe consisting of full-length clones of Hop stunt viroid, Citrus
      exocortis viroid, Citrus bent leaf viroid and CVd-III. The CVd-Multiprobe was
      tested against RNA transcripts of the four viroids and RNA extracts from plants
      singly infected with CEVd or HSVd or multiply infected with different CVds. The
      viroids were effectively diagnosed with the DIG labeled CVd-Multiprobe when
      tested by Northern hybridization or dot blot analyses. The CVd-Multiprobe does
      not provide information on the specific viroid resulting in a positive signal.
      However, this should not be considered as a problem, since most citrus
      certification programs will discard budwood source trees infected with any of the
      known CVds.

PMID- 16991000
TI  - Variation analysis of two cucumber mosaic viruses and their associated satellite
      RNAs from sugar beet in China.
AB  - Two cucumber mosaic virus (CMV) isolates XJ1 and XJ2 were obtained from sugar
      beet showing yellow mosaic symptom in Shihezi, Xinjiang Uigur municipality of
      China. The coat protein gene of the two CMV isolates and their associated
      satellite RNAs were amplified by reverse transcriptase polymerase chain reaction
      (RT-PCR) and were cloned and sequenced. Comparison of CP gene sequences showed
      that XJ1 and XJ2 have the highest sequence identity with that of CMV-Danshen
      (97.8%) and CMV-SD (98.7%), respectively. Two types of satellite RNAs (XJs1 and
      XJs2) were found to be associated with the two CMV isolates consisting of 384
      nucleotides and 336 nucleotides, respectively. Sequence comparisons revealed that
      XJs1 and XJs2 were most closely related to CS2-sat and CS1-sat, respectively,
      with 98.9% and 98.5% nucleotide sequence identity. Phylogenetic analysis of
      nucleotide sequence and deduced amino acid sequence of coat protein gene revealed
      that XJ1 and XJ2 belong to subgroup IB but there exist some variation between
      them. Parallel analyses of nucleotide sequence of XJsl and XJs2 suggested that
      these two satellite RNAs probably originated from China.

PMID- 16991002
TI  - Amino acids 1 to 422 of the spike protein of SARS associated coronavirus are
      required for induction of cyclooxygenase-2.
AB  - The causative agent of severe acute respiratory syndrome (SARS) has been
      identified as SARS-associated coronavirus (SARS-CoV). To evaluate the molecular
      mechanisms involved in the viral infection, in this study, we investigated the
      role of SARS-CoV Spike (S) protein in the regulation of cyclooxygenase-2 (COX-2).
      Expression of COX-2 stimulated by the S protein was verified by RT-PCR and
      western blot assay. To explore the relationship between S and COX-2, we
      constructed a series of plasmids containing truncated N-terminal fragments of the
      SARS-CoV S gene (designated from Sa to Si), which encoded truncated S proteins,
      and investigated whether these truncated proteins could induce effective
      expression of COX-2 in 293T cells. Our results showed that S(d) that encoded a
      truncated S protein with 422 amino acid residues (from 1 to 422 aa), a part of
      672 amino-acid S1 subunit is crucial for the induction of COX-2 expression.
      Immunofluorescence examinations also give the evidence that these N terminal 422
      amino acids of the S protein were also required for the correct localization of
      the protein. We also compared S protein sequences of SARS-CoV isolated during the
      SARS break with that from palm civets, a possible source of SARS-CoV found in
      humans. S protein residues (344, 360), which mutated in the epitome from palm
      civet to human being were characterized in 3D modeling of 252-375 amino acid
      fragment. Collectively, these results indicate that S protein of SARS-CoV induces
      the expression of COX-2 and an N-terminal fragment of the Spike protein is
      crucial for the induction. Our finding may provide clue for the induction of
      inflammation by SARS-CoV and cast insight into the severity of the SARS epidemic.

PMID- 16991001
TI  - Sequence and function of canine herpesvirus alpha-transinducing factor and its
      interaction with an immediate early promoter.
AB  - The sequence of the alpha-transinducing factor (alpha-TIF) of canine herpesvirus
      (CHV-l) was determined. Alignment of the predicted CHV-1 alpha-TIF amino acid
      sequence with other alpha-TIF homologues reveals a core region of similarity with
      divergent amino and carboxyl termini. Analysis of the CHV-1 infected cell protein
      4 promoter region identified a region containing nine copies of a 52 bp repeat
      that showed significant up-regulation of transcription by alpha-TIF. This region
      contained an imperfect 'TAATGARAT' motif, the binding site for herpes simplex
      virus 1 alpha-TIF, with an imperfect Oct-1 binding site immediately following.
      The infectious laryngotracheitis virus alpha-TIF was also shown to up-regulate
      transcription through this region of the promoter. Transfection of CHV-1 genomic
      DNA failed to yield infectious virus in canine kidney cell lines. Co-transfection
      of genomic DNA and an alpha-TIF expression plasmid resulted in virus plaques,
      indicating a potential essential role for alpha-TIF in CHV-1 infection.

PMID- 16991003
TI  - Transgenes consisting of a dsRNA of an RNAi suppressor plus the 3' UTR provide
      resistance to Citrus tristeza virus sequences in Nicotiana benthamiana but not in
      citrus.
AB  - In an attempt to utilize post-transcriptional gene silencing (PTGS) as a means to
      impart resistance against Citrus tristeza virus (CTV) into citrus plants, the p23
      + 3'UTR sequence (p23U) of the VT strain of CTV was engineered to fold into a
      double-stranded (ds) RNA structure. The resulting construct (p23UI) was
      introduced into Nicotiana benthamiana and Alemow (Citrus macrophylla) plants by
      Agrobacterium-mediated transformation. Transgenic p23UI- N. benthamiana were
      resistant to infection with a viral vector made of Grapevine virus A (GVA) + p23U
      (GVA-p23U), as indicated by the absence of the chimeric virus from inoculated
      plants. Inoculation of transgenic p23UI Alemow plants with CTV resulted in
      delayed appearance of symptoms in 9 out of the 70 transgenic plants. However,
      none of the plants showed durable resistance, as indicated by the obtaining of
      similar Northern hybridization signals from both transgenic and non-transgenic
      citrus plants. The possible causes for the failure of transgenic citrus plants to
      confer durable resistance to CTV are discussed.

PMID- 16991004
TI  - Modification of SARS-CoV S1 gene render expression in Pichia pastoris.
AB  - S1 gene fragment containing receptor-binding region was amplified by several sets
      of primers using Over-Lap PCR. The native S1 gene was modified at A + T abundant
      regions; n.t.777-1683, n.t.1041-1050, n.t.1236-1248, n.t.1317-1335, n.t.1590
      1605; based on the same amino acid sequences. The modified gene was cloned into a
      yeast expression vector pPIC9K. The resultant plasmid pPIC9K- S1 was transformed
      into Pichia pastoris GS 115 and the protein expression was induced with methanol.
      SDS-PAGE confirmed that the recombinant SI was secreted in the supernatant of
      induced GS 115. The protein yield reached 69 mg/l. ELISA and Western blot
      demonstrated that the S1 could react with the convalescent sera of people
      infected by SARS-CoV. Furthermore, ligand blot assay showed that the recombinant
      S1 could react with ACE2, the receptor of SARS-CoV. The molecular mass of
      expressed S1 was about 70 kDa, which was higher than that of the 30 kDa expected.
      PNGase F deglycosylation resulted in a protein band of 30 kDa. In conclusion, the
      S1 gene modification rendered the high-level expression of S1 in P. pastoris GS
      115 and the protein was secreted as a biologically active form which was
      hyperglycosylated.

PMID- 16991005
TI  - Enhanced immunogenicity to food-and-mouth disease virus in mice vaccination with
      alphaviral replicon-based DNA vaccine expressing the capsid precursor polypeptide
      (P1).
AB  - Recently, alphavirus replicon-based DNA vaccines, also known as suicidal DNA
      vaccines, have emerged as an important strategy to enhance the potency of DNA
      vaccines. In this study, two different types of DNA vaccines encoding the capsid
      precursor polypeptide (P1) of foot-and-mouth disease virus (FMDV) were
      constructed and the immunogenicity were investigated and compared in mouse model.
      The first DNA vaccine, pcDP1, is a conventional plasmid DNA vaccine in which P1
      was driven directly by a cytomegalovirus promoter. The second DNA vaccine,
      pSCAP1, is a Semliki Forest virus (SFV) replicon-based DNA vaccine encoding the
      same antigen. In vitro expression and characterization indicated that two vaccine
      vectors could correctly produce the P1 antigen. However, pSCAP1 could induce
      obvious apoptosis of the transfected cells. After immunization in BALB/c mice,
      the P1-specific ELISA antibodies, neutralizing antibodies, as well as lymphocyte
      proliferative responses induced by pSCAP1 were significantly higher than those
      obtained in mice immunized with pcDP1. Notably, mice immunized with the pSCAP1
      had the determined ability of clearing virus in their sera after FMDV challenge.
      These results indicate that the SFV replicon-based DNA vaccine pSCAP1 are more
      effective than conventional DNA vaccine and it can be considered a promising
      approach for the development of a safety and efficacious vaccine against FMDV.

PMID- 16991006
TI  - Complete genome sequence and phylogenetic analysis of hepatitis B virus (HBV)
      isolated from Mongolian patients with chronic HBV infection.
AB  - Although there is a report of a high rate of hepatitis B virus (HBV) infection in
      Mongolia, the entire nucleotide sequence of HBV circulating among Mongolian
      patients has not been reported. To obtain the complete nucleotide sequence of the
      Mongolian HBV, viral DNA was extracted from sera of patients with HBV infection.
      Six Mongolian HBV strains were amplified by PCR. Complete genomic sequences were
      determined for two Mongolian HBV isolates, MBT181 and MMU36. The entire genome of
      Mongolian HBV isolates was 3,182 bp long and genetic distance between Mongolian
      HBV isolates was 3.2%. Precore stop codon resulting from a guanine to adenine
      mutation at nucleotide 1,896 was detected in MBT181 strain. Based on phylogenetic
      analysis, the six Mongolian isolates were classified as genotype D.

PMID- 16991007
TI  - The translational and transcriptional initiation sites of BmNPV lef-7 gene.
AB  - The predicted open reading frame of lef-7 from Bombyx mori nucleopolyhedrovirus
      (BmNPV) is 45 bp longer at the 5'-terminal and harbors a 42 bp deletion towards
      the 3' terminal end compared to that of Autograph californica mlulticapsid NPV
      (AcMNPV). In the present study, to determine whether the BmNPV lef-7 is
      translated from an initiation site different from that of AcMNPV lef-7, the
      translational and transcriptional initiation sites of BmNPV lef-7 were examined.
      A BmNPV mutant, Bmlef7M1(-) was constructed by deleting 11 nucleotides (nt)
      including the predicted initiation codon ATG. Western blot analysis demonstrated
      that the size of LEF-7 in BmNPV and Bmlef7M1(-)-infected cells was identical. The
      LEF-7s in BmNPV and Bmlef7M1(-)-infected cells were both localized in the nuclei
      as observed using confocal microscopy. Therefore, the presumed initiation codon
      ATG (at 97059 nt of BmNPV genome) appears to be non-functional for lef-7
      translation. The 5'-RACE analysis revealed that transcription of lef-7 mRNA in
      BmNPV and Bmlef7M1(-)-infected cells both initiated from an ATCATT motif located
      26 nt upstream of the second ATG (located at 97014 nt on BmNPV genome), and 20 nt
      downstream of the presumed initiation codon.

PMID- 16991008
TI  - The quantification of prion gene expression in sheep using real-time RT-PCR.
AB  - Determination of the transcription level of cellular prion protein (PrP(C)) is
      essential for understanding its poorly explained role in organisms. Scrapie in
      sheep is the prototype of all prion diseases. However, the expression of prion
      protein (PrP) mRNA in sheep has not been quantified in great detail. Herein we
      report on measurement of sheep PrP mRNA using absolute quantitative real-time
      reverse transcription and polymerase chain reaction (RT-PCR). Total RNA was
      isolated from seven different regions of the central nervous system (CNS) and six
      peripheral organs of 18 sheep and PrP mRNA was quantified by real-time RT-PCR
      using an externally calibrated standard curve constructed with the recombinant
      PrP plasmid. The results showed that high levels of PrP mRNA were expressed in
      all seven regions of the brain examined, with obex and neocortex expressing the
      highest PrP, followed by cerebellum, spinal cord, hippocampi, conarium and
      thalamus, In peripheral organs examined, lymph node showed a level of PrP
      expression similar to that in overall brain, whereas spleen, heart, liver and
      lung showed moderate level of expression and kidney showed the lowest expression.
      Our study provided the first quantitative, tissue-specific data of PrP mRNA
      expression in sheep for further studies of pathogenesis of prion diseases.

PMID- 16991009
TI  - Expression of full-length and truncated Rep genes from Mungbean yellow mosaic
      virus-Vigna inhibits viral replication in transgenic tobacco.
AB  - Mungbean yellow mosaic virus-Vigna (MYMV-Vig) is a bipartite geminivirus that
      causes a severe yellow mosaic disease in blackgram. An assay was developed to
      study MYMV-Vig replication by agroinoculation of tobacco leaf discs with partial
      dimers of the virus. This assay, in a non-host model plant, was used to evaluate
      pathogen-derived resistance contributed by MYMV-Vig genes in transgenic plants.
      Viral DNA accumulation was optimum in tobacco leaf discs cultured for 10 days
      after infection with Agrobacterium tumefaciens strain Ach5 containing partial
      dimers of both DNA A and DNA B of MYMV-Vig. Transgenic tobacco plants with MYMV
      Vig genes for coat protein (CP), replication-associated protein (Rep)-sense, Rep
      antisense, truncated Rep (T-Rep), nuclear shuttle protein (NSP) and movement
      protein (MP) were generated. Leaf discs from transgenic tobacco plants,
      harbouring MYMV-Vig genes, were agroinoculated with partial dimers of MYMV-Vig
      and analyzed for viral DNA accumulation. The leaf discs from transgenic tobacco
      plants harbouring CP and MP genes supported the accumulation of higher levels of
      MYMV-Vig DNA. However, MYMV-Vig accumulation was inhibited in one transgenic
      plant harbouring the Rep-sense gene and in two plants harbouring the T-Rep gene.
      Northern analysis of these plants revealed a good correlation between expression
      of Rep or T-Rep genes and inhibition of MYMV-Vig accumulation.

PMID- 16991010
TI  - Gabor filters and phase portraits for the detection of architectural distortion
      in mammograms.
AB  - Architectural distortion is a subtle abnormality in mammograms, and a source of
      overlooking errors by radiologists. Computer-aided diagnosis (CAD) techniques can
      improve the performance of radiologists in detecting masses and calcifications;
      however, most CAD systems have not been designed to detect architectural
      distortion. We present a new method to detect and localise architectural
      distortion by analysing the oriented texture in mammograms. A bank of Gabor
      filters is used to obtain the orientation field of the given mammogram. The
      curvilinear structures (CLS) of interest (spicules and fibrous tissue) are
      separated from confounding structures (pectoral muscle edge, parenchymal tissue
      edges, breast boundary, and noise). The selected core CLS pixels and the
      orientation field are filtered and downsampled, to reduce noise and also to
      reduce the computational effort required by the subsequent methods. The
      downsampled orientation field is analysed to produce three phase portrait maps:
      node, saddle, and spiral. The node map is further analysed in order to detect the
      sites of architectural distortion. The method was tested with 19 mammograms
      containing architectural distortion. In a preliminary experiment, a sensitivity
      of 84% was obtained at 7.8 false positives per image.

PMID- 16991011
TI  - [Rheumatoid arthritis and cardiovascular complications].
AB  - Rheumatoid arthritis is associated with increased morbidity and mortality due to
      cardiovascular events. Elevated concentrations of acute-phase proteins and
      cytokines and endothelial dysfunction, demonstrated also by lack of traditional
      risk factors, play an important role in these complications. Antirheumatic drug
      treatment can modify the frequency and severity of cardiovascular events.

PMID- 16991012
TI  - [Osteitis. Infections of the locomotive system].
AB  - Infections of the locomotive system appear in many different forms such as acute
      inflammation of joints or bone following injury or surgical or chronic processes,
      often lasting for years. They demand an exact treatment plan not only to remove
      necrotic tissue but also for reconstruction of defects. A special problem is
      infection following alloplastic reconstruction of joints or spine. Multiple
      surgical procedures are required to hinder reinfection, restore function, and
      assure acceptable patient quality of life.

PMID- 16991014
TI  - Real-time quantitative assay of HCV RNA using the duplex scorpion primer.
AB  - A novel real-time quantitative method for detecting HCV in serum was established
      in which the duplex scorpion primer was used to provide a unimolecular probing
      mechanism for hybridizing the highly conserved 5' noncoding region (5' NCR) of
      the HCV genome specifically. Through methodological evaluation, we found this new
      method had a wide linearity, high sensitivity, repeatability and specificity.
      Compared to the commercial TaqMan method, this method was found to be more
      sensitive and less costly, and the final results were obtained more quickly.
      Therefore, it could be applied to diagnose and monitor HCV infection in clinical
      practice.

PMID- 16991015
TI  - [Improving the publication rate of Spanish researchers in good journals].
AB  - Five obstacles are described that currently prevent Spanish researchers in the
      psychological sciences from publishing more frequently in journals of high impact
      factor. These are: a) a general lack of confidence in your ability; b) a tendency
      for your papers to be driven more by speculation rather than data; c) excessive
      length of submitted manuscripts; d) higher than expected rates of drop-out and
      non-participation in studies, and e) lack of independence from pharmaceutical
      companies. Although many of these problems will require long-term structural
      changes, others can be addressed immediately and yield improvement rapidly.

PMID- 16991013
TI  - [Regulated hypothermia after cardiac arrest. A glimpse into the future].
AB  - The introduction of therapeutic mild hypothermia after cardiac arrest allows the
      neuronal damage caused by global cerebral ischemia to be advantageously
      influenced for the first time. Currently, hypothermia is induced by external or
      internal cooling of the patient (forced hypothermia). However, this results in
      activation of counter-regulation mechanisms which could be possible risk factors
      for the patient. The aim of this article is to give a review of possible, but at
      present only experimental, methods which could allow the body temperature set
      point to be decreased pharmacologically (regulated hypothermia). Various classes
      of substances will be discussed based on their effect on thermoregulation and
      their performance in animal experiments on cerebral ischemia.

PMID- 16991016
TI  - [Subjective experience with antipsychotics: quantitative evaluation].
AB  - INTRODUCTION: The subjective experience of psychotic patients with neuroleptics
      has been the purpose of many studies, considering its importance in treatment
      adherence, quality of life and outcome. Many authors have developed measurement
      instruments applicable in everyday clinical practice. The scale objectives defer
      in hues, but have the subjective perspective in common. METHOD: Questionnaires
      designed for evaluating subjective experience with antipsychotics, appearing in
      PUBMED during the last 40 years, have been collected. RESULTS: Ten scales for
      evaluating the subjective experience with antipsychotics: NDS, DRI, DAI-30, DAI
      10, ROMI, SWN, SWN (short version), MARS, ANT and PETiT, were found. Their
      advantages and limitations have been analyzed. CONCLUSIONS: We have checked out
      that the contents of each scale do not overlap. It is proposed to differentiate
      between ((dysphoria response to neuroleptics)) as an acute effect and the
      ((subjective experience)) as complex effect of long term compliance.

PMID- 16991017
TI  - [Estimation of prevalence, incidence and sex ratio of transsexualism in Catalonia
      according to health care demand].
AB  - OBJECTIVE: To estimate the epidemiology of transsexualism in the autonomous
      community of Catalonia according to data gathered at the Hospital Clinic of
      Barcelona, the single public hospital providing specialized psychiatric and
      endocrinological care for transsexual patients in this community. PATIENTS AND
      METHODS: Prevalence was calculated on the basis of the total number of patients
      diagnosed of transsexualism (ICD-10, F64.0) at the Hospital Clinic and living in
      Catalonia, and the incidence by counting all new cases of transsexuals for the
      last 5 years, based on the population census between 15 and 65 years of age.
      RESULTS: During the period from 1996 through 2004 a total of 201 subjects were
      referred to this hospital with complaints of gender dysphoria. Transsexualism was
      diagnosed in 182 patients, 161 of whom were living in Catalonia. This yields a
      prevalence rate in Catalonia of 1:21,031 males and 1:48,096 females. The sex
      ratio was 2.6. Annual incidence in the last five years was 0.73/100,000/year.
      DISCUSSION: The low prevalence compared with recently published data from
      European Union countries may be due to the relatively few years of data
      collection and to the low clinical demand because surgical procedures costs are
      not covered by the public health insurance. In contrast, the high incidence may
      be due to the increasing demand since 2000, when a more benevolent and tolerant
      social climate in Spain started.

PMID- 16991018
TI  - [Effect to the serotonin transporter gene (5-HTT) on personality dimensions in
      individuals without psychopathology].
AB  - INTRODUCTION: The aim of the present study was to assess the association between
      the serotonin transporter gene and the Temperament and Character Inventory (TCI)
      personality dimensions in subjects without psychopathology. METHOD: Fifty seven
      individuals without psychiatric symptoms were assessed with the SCL-90, and the
      TCI. In all subjects a peripheral blood sample was taken to determine their
      genotypes, after informed consent. Three groups were formed according to the 5
      HTT genotype: SS, SL and LL, and the TCI results were compared. RESULTS: There
      was no association among the 5-HTT genotypes and any of the TCI subscales. There
      were also no statistical differences among any of the three groups divided by
      genotype only according to the TCI scores, as well as when compared with
      historical controls. CONCLUSIONS: These results are consistent with other studies
      that have not found associations among the different measurements of personality
      and 5-HTT genotypes. Likewise, our data suggest that our sample can be useful as
      a source of controls for later studies. This is the first study assessing TCI
      dimensions and the 5-HTT gene in the Mexican population.

PMID- 16991019
TI  - [Swallowing phobia: symptoms, diagnosis and treatment].
AB  - INTRODUCTION: Choking phobia (or swallowing phobia) is characterized by a fear of
      swallowing foods, liquids or pills, sometimes after an episode of choking on
      food. METHODS: Forty-one case reports on swallowing phobia from 1978 to 2005 were
      studied. Clinical and therapeutic variables of the disorder were studied.
      RESULTS: It appears to occur more often in females (two-thirds of the cases) and
      has a high comorbidity with anxiety disorders (panic disorder, 41 %; obsessive
      conditions, 22 %, and separation anxiety, 15 %). Life-events and eating traumatic
      antecedents are frequently present (44% and 56% cases, respectively). Cognitive
      behavioral treatments have been of proven efficacy, as well as anti-panic drugs
      (alprazolam, lorazepam, bromazepan, imipramine, clomipramine, fluoxetine,
      paroxetine) with a remission rate of 58.5%. Gender and treatment differences are
      also analyzed.

PMID- 16991020
TI  - [Insight, neurocognition and psychopathology in schizophrenia].
AB  - INTRODUCTION: In recent years, research has been aimed at finding variables
      mediating between neurocognition and psychosocial functioning in schizophrenia,
      proposing insight as one of these variables. Some authors have found associations
      between insight and functional outcome, and between insight and symptomatology,
      although these associations remain unclear. These different findings could be
      explained by the insight definition used. The current study evaluates insight
      unidimensionally and multidimensionally and studies its relationship with
      cognitive and psychopathological variables. METHODS: The sample consisted of 94
      subjects admitted to an outpatient Psychosocial Rehabilitation Program, all
      diagnosed of schizophrenia according to ICD-10 diagnostic criteria. A brief
      version of the Neuropsychology Battery Test Barcelona and the Wisconsin Card
      Sorting Test were used to evaluate cognitive variables. The Positive and Negative
      Syndrome Scale (PANSS) was used to evaluate psychopathology. Insight was assessed
      with the PANSS item ((lack of judgment and insight)), and with a semi-structured
      interview. RESULTS: Two insight factors were found, one including more specific
      knowledge about the disease and its consequences (cognitive factor), that is
      related to executive functions, and another referring to unspecific knowledge
      about suffering from an illness and the need for treatment (psychotic factor).
      Each factor was statistically related to positive symptoms and superior cognitive
      functions. CONCLUSIONS: These findings support a relationship between insight and
      low cognitive performance.

PMID- 16991021
TI  - [Analysis of prescription patterns of antipsychotic agents in psychiatry].
AB  - INTRODUCTION: We describe the different diseases in which conventional and second
      generation antipsychotic (APS) prescriptions are made. METHOD: Observational,
      retrospective, multicenter study based on the review of 300 clinical records of
      public and private sites, hospital and out-patient clinics, located in Salamanca,
      Vigo, Bilbao, Barcelona, Valencia, Oviedo and Malaga. RESULTS: The mean age of
      the population studied was 42 +/- 17 years; 56.6 % were men. Atypical drugs (67
      %) were used basically versus classical ones (33 %). Classical APS are basically
      prescribed in bipolar disorder with/without psychotic symptoms (20.6 %),
      schizophrenia (18.3%) and delusional disorder (11.5 %). Atypical APS are
      fundamentally prescribed in schizophrenia (31.5 %), bipolar disorders
      with/without psychotic symptoms (12.5 %) and other psychotic disorders (8.9 %).
      When the psychotic disorders are considered by groups (schizophrenia, bipolar
      disorder with psychotic symptoms, delusional disorder and other psychotic
      disorders), classical APS are used in 47.4 % and atypical APS in 62.5%. APS were
      used ((outside the indication)) (off-label) in 32.8%, including resistant
      depressions, serious obsessive-compulsive disorder and borderline personality
      disorder, with similar percentages for both conventional and atypical ones. In
      dementia, atypical APS were used in 5.1 % versus 1.5 % of the conventional ones.
      The most frequent reasons for prescription of classical APS were control of
      psychotic symptoms (33.6 %), aggressiveness-agitation (31.3 %), severe insomnia
      (16 %), impulsivity (6.9 %) and severe anxiety (6.1 %). Atypical APS were
      preferably used in the control of psychotic symptoms (58.8%) and aggressiveness
      agitation (25.5%). CONCLUSIONS: The use of APS basically occurs within their
      authorized indications (67.2 %). The off-label use (32.8 %) occurs both for the
      classical as well as atypical APS and occurs in serious diseases in which there
      are no alternative treatments.

PMID- 16991022
TI  - [Psychopathology associated to attention deficit hyperactivity disorder in school
      age children].
AB  - INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) represents a
      frequent and highly comorbid disorder in children and adolescents. Comorbidity
      differs according to ADHD subtype and gender and has been reported to have a
      direct effect on the severity of ADHD. METHODS: A descriptive, cross-sectional
      study was designed to determine the patterns of ADHD comorbidity in 102 children,
      aged 6 to 12 years, who attend the outpatient services of a child psychiatric
      hospital in Mexico City. The evaluation was performed using the Child Behavior
      Checklist (CBCL). RESULTS: The sample had about five comorbid disorders. The
      hyperactive-impulsive subtype had more severe externalizing symptoms, while the
      combined subtype had a higher severity of anxious depressive symptoms, delinquent
      behavior and internalized symptoms. Somatic complaints were more frequent in
      boys. A linear regression analysis showed that the severity of attention problems
      was influenced by the severity of aggressive behavior. CONCLUSIONS: School age
      children who came to psychiatric attention services with ADHD are highly
      comorbid. The comorbidity increases the severity of attention problems,
      particularly in patients with the hyperactive-impulsive or combined subtypes.

PMID- 16991023
TI  - [Historical review of the borderline personality disorder concept].
AB  - INTRODUCTION: The concept of borderline syndrome is the subject of current debate
      because of its ambiguity and lack of homogeneity. Furthermore, the concept is
      rejected by many authors as a common category for atypical and non-specific
      disorders that cannot be classified elsewhere. The current use of the term
      borderline seems to be more a consequence of its historic use than its true
      clinical meaning. There is discrepancy on whether this term determines a level of
      severity, an organization of personality or a defined syndromic entity. In 1938,
      Stern was the first author to use the term borderline, and it was not introduced
      in the DSM III until 1980. OBJECTIVE: This work makes a historical review of the
      use of the term borderline and also of those terms that have been used to define
      patients with the same characteristics. CONCLUSION: The different schools
      (psychoanalytic, biological, eclectic and biosocial) have different concepts on
      the term borderline. There is still no concise and exact definition for the
      diagnostic criteria of borderline and it is even possible the best term for this
      group of patients has still not been determined. It will be important to consider
      the contributions of the DSM V or ICD 11 in the next years.

PMID- 16991024
TI  - [Melatonin therapeutic use in psychiatry: a 39 year bibliographic study].
AB  - INTRODUCTION: The therapeutic uses of melatonin in psychiatry are reviewed.
      METHODS: Data source and search strategy: a 39 year period search covering a 39
      year period (1966-2004) was carried out using Medline data base. The search
      strategy consisted in the combination of the key words ((mental disorders or
      psychiatry)) and ((melatonin and therapeutic use)). Two restrictive criteria were
      applied: a) selection of studies carried out in humans, and b) only randomized
      controlled trials were admitted RESULTS: 56 articles were found. Twelve were
      excluded because they were not directly related to the study aim. Melatonin was
      used in 44 articles related to different clinical conditions. It was used because
      of its hypnotic and/or resynchronizing actions in 93.2 % of the articles, while
      in 4.5 % of the articles melatonin was used due to its antioxidant properties.
      CONCLUSIONS: The main use of melatonin as a therapeutic agent in psychiatry is in
      sleep disorders and its use in other psychiatric is minor.

PMID- 16991025
TI  - [Beta blocker induced depression. A case report].
AB  - INTRODUCTION: Although association between beta blockers and depression has been
      reported since decades ago, the subject is still controversial. Most evidence
      supporting an association has been based on case reports or case series.
      Epidemiologic studies and randomized clinical trials have not generally supported
      this association. If this association exists, possible causes of disparity of
      findings may include methodological difficulties, and/or weak association. CASE
      SUMMARY: We present a case of a 67 year old woman, without personal history of
      psychiatric illness or stress factors, who develops a depressive episode after
      initiating treatment with atenolol. The symptoms remitted rapidly when atenolol
      was discontinued, and an antidepressant was prescribed during a short period.
      CONCLUSIONS: This case report suggests the existence of an association between a
      beta blocker, atenolol, and depression.

PMID- 16991027
TI  - [Angiographic assessment of functionally insignificant left main coronary artery
      stenoses: reliability compared to intracoronary pressure measurement].
AB  - BACKGROUND AND OBJECTIVE: Left main coronary artery disease (LMCA) is still a
      widely accepted indication for coronary artery bypass surgery. Intermediate LMCA
      disease, however, often cannot be evaluated reliably on the basis of clinical and
      angiographic information alone. The deferral of surgical revascularization based
      on fractional flow reserve (FFR) measurements has been shown to be safe and
      feasible when taking an FFR value of (3) 0.75 as cutoff. This study was performed
      to compare the accuracy of visual angiographic assessment of intermediate LMCA
      stenoses by experienced interventional cardiologists with functional assessment
      by FFR in a patient population with excellent long-term outcome after deferral of
      surgery on the basis of FFR measurements. PATIENTS AND METHODS: 24 of 51
      consecutive patients with intermediate LMCA disease were deferred from surgery
      based on an FFR value of > or = 0.75. Each angiogram was retrospectively reviewed
      independently by three experienced interventional cardiologists. Reviewers were
      blinded to initial FFR results, clinical data, and clinical outcome and asked to
      classify each lesion as SIGNIFICANT (FFR < 0.75), NOT SIGNIFICANT (FFR > or =
      0.75), or UNSURE if the observer was unable to make a decision based on the
      angiogram. RESULTS: Mean follow-up was 29 +/- 13.6 months. No death or myocardial
      infarction was observed, event-free survival was 69 %. When taking the "unsure"
      classifications into consideration the individual reviewers achieved correct
      lesion classification with respect to FFR results on average in 58 % to 82 % of
      cases. Interobserver variability resulted in only 46 % of cases in concordant
      lesion classification (3 agreements or 2 agreements and 1 "unsure" evaluation).
      The number of concordant agreements between the individual pairs of reviewers did
      not exceed the rate of coincidental agreements that could be expected to result
      from simple guessing (mean KAPPA coefficient 0.04). More than 50 % of patients
      with excellent long-term outcome after deferral of surgery would potentially have
      undergone operative revascularization if consensual decision making had been
      solely based on angiographic lesion assessment. CONCLUSION: The functional
      significance of intermediate or equivocal LMCA lesions should not be based on
      visual assessment alone, even when performed by experienced interventional
      cardiologists.

PMID- 16991028
TI  - [In-hospital resuscitation. Concept of first-responder resuscitation using semi
      automated external defibrillators (AED)].
AB  - BACKGROUND AND OBJECTIVE: The prognosis after in-hospital resuscitation has not
      significantly improved in the last 40 years. This account presents the results
      over a three-year period of a hospital-wide emergency plan which implements the
      use of an automated external defibrillator (AED) by the first responder to the
      emergency call. BACKGROUND AND OBJECTIVE: 15 "defibrillator points" were
      installed, which could be reached within 30 s from all wards, out-patient
      departments and other areas, thus making them accessible for immediate
      defibrillator application. The hospital personnel is trained periodically in the
      alarm sequence, cardiopulmonary resuscitation and use of the defibrillator. Data
      on 57 patients who had sustained a cardiac arrest were prospectively recorded and
      analysed. RESULTS: In 46 patients (81%) the "on-the-spot" personnel (first
      responder) was able to apply AED before arrival of the hospital's resuscitation
      team. Mean period between arrest alarm and activation of the AED was 2.2 (0.7
      4.7) min. Ventricular fibrillation or ventricular tachyarrhythmia was recorded in
      40 patients, making immediate shock delivery by AED possible. Restoration of the
      circulation was achieved in 23 (80%) of the patients and 20 (50%) were discharged
      home, 17 (43%) without neurological deficit. The high proportion of first
      responder AED applications and evaluation of the personnel training indicate a
      wide acceptance of the emergency plan among the personnel. CONCLUSION: An
      immediate resuscitation plan consisting of an integrated programme of early
      defibrillation is feasible and seems to achieve an improved prognosis for
      patients who have sustained an in-hospital cardiac arrest.

PMID- 16991029
TI  - [Recurrent autoreactive pericardial effusion. Impact of an aetiological
      classification of pericarditis].
AB  - HISTORY: A 36 year-old man suffered from fever, fatigue, pleurodynia and
      precordial discomfort. His family physician suspected febrile tracheobronchitis
      and treated it with ampicillin for 5 days. Because symptoms persisted an ECG was
      done which suggested acute myocardial infarction. The patient underwent an
      emergency coronary angiography which excluded coronary artery disease and aortic
      dissection. Pericarditis was suspected and the patient put on aspirin, 500 mg/d.
      Because of persisting cardiac symptoms an echocardiography was performed which
      revealed systolic separation between epi- and pericardium, characteristic of a
      small pericardial effusion after acute pericarditis. The symptoms improved after
      one week of treatment with diclofenac and the ECG had become normal. Two months
      later the patient was seen at our cardiac outpatient clinic. He had night sweats,
      sporadic precordial pain and severe dyspnoe. INVESTIGATIONS: Further
      investigations revealed tachycardia (120/min), hypotension (95/70 mm Hg), pulsus
      paradoxus and jugular vein sustension. Echocardiography revealed a large
      pericardial effusion ("swinging heart"), which explained the low voltage and the
      electrical alternans in the ECG. TREATMENT AND COURSE: Pericardiocentesis was
      carried out the same day to relieve the tamponade. It was followed by
      pericardioscopy and epi- as well as pericardial biopsy. 485 ml of a serous
      effusion were drained. Cytology and histology demonstrated a lymphocytic
      fibrinous pericarditis. Polymerase chain reaction (PCR) on viral and bacterial
      RNA and DNA of potentially cardiotropic agents remained negative. The pigtail
      catheter was left in place and 80 mg of gentamycin were given intrapericardially
      on day 1 and 2, followed by 500 mg of crystalloid triamcinolone acetate after the
      PCR was found to be negative. Oral treatment with 0.5 mg colchicine three times a
      day (off-label use) was started and maintained for 6 months. After 9 months no
      effusion was detected and the patient was free of symptoms. CONCLUSIONS: After
      exclusion of bacterial and viral pericardial infection, a high single dose of
      intrapericardial triamcinolone combined with long-term oral colchicine has proven
      to be a highly efficacious treatment of autoreactive pericarditis which will
      avoid relapses in most cases.

PMID- 16991031
TI  - [Resynchronization therapy for heart insufficiency].

PMID- 16991032
TI  - [Treatment of atrial fibrillation -- the goal is rhythm control].

PMID- 16991033
TI  - [Treatment of atrial fibrillation -- the goal is frequency control].

PMID- 16991034
TI  - [Background and indications for distal protection devices in percutaneous
      coronary interventions].

PMID- 16991035
TI  - [ICD-implantation--for which patients is its value for primary prevention
      secure?].

PMID- 16991036
TI  - [Ischemic pre- and postconditioning].
AB  - One or several short cycles of ischemia/reperfusion before (preconditioning) or
      after (postconditioning) a sustained coronary occlusion with subsequent
      reperfusion reduce the ultimate infarct size. The protection is potent, but
      limited to a narrow time frame. In animal experiments a complex signal
      transduction cascade was identified which results specifically in a reduction of
      reperfusion injury. There is evidence for both ischemic pre-and postconditioning
      in patients with coronary artery disease.

PMID- 16991038
TI  - [Persistent CK elevation after CSE inhibitor therapy].

PMID- 16991037
TI  - [Persistent CK elevation after CSE inhibitor therapy].

PMID- 16991039
TI  - [Strategical approach for the treatment of the horizontal laxity of the lower
      lid].
AB  - Horizontal laxity of the lower lid is often unrecognized and leads to a wrong
      treatment. The proper analysis of periorbital anatomy is most important to
      identify the pathophysiology in each case. Typically, the lateral canthal tendon
      becomes lax, resulting in eyelid malpositions. The mainstay of treatment includes
      tightening of either the inferior crus of the lateral canthal tendon or
      repositioning the entire lateral canthal tendon. The types of procedure performed
      will be reviewed in detail. The evaluation of the tarsal strip and the lateral
      dermal orbicular pennant flap as unique reconstructive tools and as adjuncts to
      aesthetic surgery will be discussed.

PMID- 16991040
TI  - [Male breast contouring after massive weight loss].
AB  - Morbid obesity is an increasing problem of our present affluent society.
      Simultaneously with a duplication of the number of obese patients in the course
      of the 20th century, a significant and continual increase can be recognized in
      patients introducing, after massive weight loss, to plastic surgeons due to
      improvements in bariatric surgery can be recognized simultaneously. The male
      breast, a body-region that symbolizes manhood and strength and often remaining as
      a deflated skin-envelope, is one of the most disturbing body regions, causing
      extreme lack of confidence in post-weight-loss patients. In this context there
      are alternative procedures which can be applied locally or in combination with
      other body-contouring procedures in flanking regions.

PMID- 16991041
TI  - [Prevascularisation strategies in tissue engineering].
AB  - INTRODUCTION: Experiments on animals have underlined the importance of
      vascularisation for biointegration and functionality of any given tissue
      engineering device. The aim of this investigation was to dissect the angiogenetic
      process in the frame of axial neovascularisation of a xenogenic solid matrix. The
      ultimate goal of this series of studies is the application of cells onto a
      prevascularised matrix, with the ambition to enhance cell survival after
      transplantation in vivo. MATERIALS AND METHODS: We performed a study in the rat
      with different vascular configurations in an isolation chamber. A disc-formed
      biogenic hard matrix (9 x 5 mm) was encased into an isolation chamber made of
      Teflon. In group 1, an arteriovenous fistula (AV loop) between the femoral
      vessels was microsurgically constructed and was placed around the matrix (n =
      15). In group 2, the vascular carrier had the form of an arteriovenous ligated
      pedicle (n = 15). Evaluation intervals were two, four and eight weeks after
      implantation. The modes of evaluation included histology, scanning electron
      microscopy of corrosion casts as well as intravital micro-magnetic resonance
      imaging (MRI). RESULTS: The arteriovenous loop as vascular carrier revealed a
      higher capacity for angiogenesis over the bundle configuration. The neo
      fibrovascular tissue displayed minimal inflammatory elements but dense
      vascularisation. Scanning electron microscopy demonstrated a vivid angiogenesis
      with rapid evolution of the vascular bead into mature, hierarchically organised
      network. Micro-MRI could be used for serial investigation in terms of flow
      measurements and detection of thrombosis. DISCUSSION: The presence of a vascular
      bed prior to cell transplantation might protect against hypoxia-induced cellular
      death, especially at central portions of the matrix, and therefore ensure
      physiological function of the device. The generation of vascularised
      bioartificial tissue substitutes might offer new modalities of surgical
      reconstruction for use in reparative medicine.

PMID- 16991042
TI  - [Histological and immunohistochemical investigations with capsular contracture
      after breast augmentation with smooth silicone gel implants].
AB  - INTRODUCTION: A prospective study was performed to analyse the cellular and
      molecular composition of fibrous capsules around silicone breast implants. The
      necessity of an exact histological classification for comparing objectively the
      different findings of capsular contracture is shown. PATIENTS AND METHODS: The
      prospective study (investigation time 1/2003 to 6/2005) included 24 female
      patients (average age: 40+/-12 years) with contracture after bilateral cosmetic
      breast augmentation with smooth silicone gel implants (Mentor). In each patient
      the baker score was determined preoperatively. Samples of capsular tissue from
      all patients were evaluated histologically and immunohistochemically and
      classified according to the histological classification introduced by
      Wilflingseder and co-workers. RESULTS: All capsules showed the same basic
      histological structure with a three-layer composition. For the correlation
      analysis we had to exclude one patient with repeated implant change. There was no
      correlation between the patient's age, time of implantation, length of implant
      period, and capsular contracture. Greater amounts of silicone particles were
      associated with increased degrees of capsular contracture (Baker: r = 0.687, n =
      23, p < or = 0.001; Wilflingseder: r = 0.784, n = 23, p < or = 0.001). High
      silicone amounts were associated with an increased local inflammation (r = 0.489,
      n = 23, p , 0.05). A moderate to severe local inflammation was found in 23
      patients (95.8%). In summary, there was a positive correlation (r = 0.797, n =
      23; p , or = 0.001) between the clinical classification (Baker score I to IV) and
      the histological classification (Wilflingseder score I to IV). CONCLUSIONS: We
      demonstrated in our study, in spite of using implants with high gel cohesiveness
      (fourth generation), the presence of vacuolated macrophages with microcystic
      structures containing silicone and silicone particles in the capsular tissue.
      Greater capsular thickness was associated with an increased number of silicone
      particles ans silicone-loaded macrophages in the peri-implant capsule. The
      histological classification introduced by Wilflingseder and co-workers takes into
      consideration this pathogenetic mechanism of inflammatory reaction which seems to
      be one of the major key factors in the development of capsular contracture.

PMID- 16991043
TI  - [Bottoming out in augmentation mammaplasty--correction and prevention].
AB  - Displacement of a breast implant beneath the original submammary fold is known as
      a rare but, in most cases, difficult to correct complication after augmentation
      mammaplasty. Suggestions for re-centering the mammary implant range from simple
      percutaneous sutures to the additional application of expensive alloplastic
      dermal grafts. Based on the latest findings concerning plastination histology of
      the fascial system of the breast and in the light of our own clinical experience
      regarding correction of implant ptosis we have developed a special treatment
      concept. When placing the implant, the vertical fibers of the submammary fold are
      saved as a precautionary measure. In cases where there is a risk of possible
      inferior displacement of the mammary implant, an individually manufactured belt
      like bandage is applied for approximately eight weeks postoperatively. In cases
      requiring the correction of a severe "bottoming out" deformity, we either lift
      the capsular shell of the implant or, if the fibrous capsule is thin and
      vulnerable, we use a special capsular flap technique resulting in a hammock that
      catches the implant at the height of the new submammary fold. Postoperative
      application of our belt-like bandage is again indispensable.

PMID- 16991044
TI  - [The balloon dissector in expander treatment: A ten-year experience in plastic
      and reconstructive surgery].
AB  - BACKGROUND: The use of the balloon dissector ("space maker") for the implantation
      of soft tissue expanders is illustrated and technical aspects and advantages are
      compared to the conventional method. PATIENTS AND METHODS: Over a 10-year period
      a group of 90 patients with evaluation records (m = 34, f = 56) was analysed
      retrospectively. The mean age was 23 years (range: 5 to 62 years). Overall, 164
      expanders were implanted and in 73 cases (44.5%) a balloon dissector was used.
      RESULTS: The mean intraoperative expander filling was increased up to 27% of the
      volume of the tissue expander after using the balloon dissector; in contrast it
      was 15% after conventional dissection. The mean duration of expansion was
      decreased by 9.8% after space maker dissection. CONCLUSION: The use of the space
      maker is a scar-sparing technique. Time of operation and overall duration of
      expansion are reduced. Patient comfort is clearly improved. The negligible costs
      of a space maker are compensated by the cost reduction due to shorter operating
      time, fewer outpatient contacts and a low complication rate. The indications for
      the use of balloon dissectors are the expansion of skin (scar correction after
      burns, trauma, tumour), breast reconstruction and augmentation, and the
      prefabrication and rapid intraoperative expansion of musculocutaneous flaps.

PMID- 16991045
TI  - [Restoration of function by microsurgical reconstruction after sarcoma excision
      in the upper limb].
AB  - The treatment of soft tissue sarcomas includes different modalities, but the
      complete excision of the tumor is the most important one. It is often difficult
      to resect the tumor completely and simultaneously restore a good function of the
      upper limb. Therefore a microsurgical reconstruction is often necessary as
      demonstrated here.

PMID- 16991046
TI  - [Otto Hilgenfeldt (1900 to 1983)--an unusual approach for finger reconstruction].
AB  - Reconstructive surgery of detached extremities, especially fingers, has a long
      historical tradition. The first clinically correctly documented cases go back to
      the 19th century. During the first and second world wars numerous reports
      appeared about the surgical care of war victims. Pioneering innovative surgical
      methods were developed by especially motivated surgeons for the reconstruction of
      these disfiguring war injuries in Europe. Because of these particular
      circumstances and the prevailing revolutionary spirit, many innovations in
      surgery were developed. The report of Otto Hilgenfeldt (1950) described his
      unusual approach in reconstructing a finger by using the great toe.

PMID- 16991047
TI  - [Long-term results following denervation of the wrist in patients with stages II
      and III SLAC-/SNAC-wrist].
AB  - INTRODUCTION: Mid-carpal arthrodesis, proximal row carpectomy and wrist
      arthrodesis are commonly cited in the literature as successful methods for pain
      reduction in patients with advanced carpal collapse (SLAC-/SNAC-wrist stages II
      and III). However, studies of isolated wrist denervation in patients who still
      possess good wrist mobility appear to be an underrepresented topic, especially in
      the German literature. PURPOSE: Based on follow-up results, it was possible to
      establish to what extent patients benefit long-term from isolated wrist
      denervation, whilst retaining wrist mobility. PATIENTS AND METHOD: 46 patients (6
      female, 40 male) with a diagnosis of SLAC-wrist (n = 10) or SNAC-wrist (n = 36)
      stages II and III underwent wrist denervation of points 1 - 4, 6, 9 and 10
      according to Wilhelm, between 1990 and 2001, following a positive denervation
      test. No previous reconstructive wrist surgery had been performed on any of the
      patients, whose average age at the time of denervation was 47 years. In 29 cases
      the dominant hand was affected, and in 22 cases the symptoms could be classified
      as post-traumatic. Post-operative follow-up was possible in 32 out of 46 cases
      (70 %), and occurred on average 6.3 years post-denervation (range 2.3 to 14
      years). RESULTS: Twelve out of 32 patients (32 %) reported to be pain-free at
      follow-up, with a post-operative period ranging from 2.3 to 11.4 years (average
      6.2 years). Six patients (18.75 %) continued to experience pain when load
      bearing, which remained unchanged over a period of several years. Three patients
      (9 %) reported pain after stress, five patients (15.6 %) the recurrence of severe
      pain, which developed on average 3.8 years post-operatively. Two patients (6.25
      %) experienced no analgesic benefits following wrist denervation, and four
      patients underwent wrist arthrodesis on average 13.5 months post-denervation, due
      to remaining or additional symptoms. Nineteen out of 32 patients subjectively
      reported a significant improvement following wrist denervation. Reassessment of
      range of movement post-denervation showed a reduction of 8.1 % in wrist
      extension/flexion, and 20 % in radio/ulna-abduction. Compared to the unaffected
      side, this represented an average loss of 28 % wrist extension/flexion, and 33.5
      % radio/ulna-abduction. An average 51 % increase in hand strength could be shown
      at follow-up, leaving an average 30 % deficit compared to the unaffected hand.
      Evaluation of these results using the Krimmer score showed a good - very good
      outcome in 20 of the 32 patients (62.5 %); six patients were found to have a
      satisfactory outcome, and six patients a poor outcome. Subjective measures of
      pain (obtained using visual analogue scales) showed a reduction from 68.13 pre
      operatively to 25.63 post-operatively. The DASH assessment (parts A and B)
      attained an average post-operative value of 17.1. CONCLUSION: Denervation of the
      wrist in patients with SLAC-/SNAC-wrist stages II and III can achieve a long-term
      elimination or reduction of pain, whilst improving hand strength, and having only
      a minimal impact on wrist range of movement. Wrist denervation should therefore
      be given preference over wrist arthrodesis, midcarpal arthrodesis or proximal row
      carpectomy in patients with good wrist mobility.

PMID- 16991049
TI  - [Evaluation of indirect costs during postoperative disability after hip
      prosthesis from the perspective of the payer].

PMID- 16991048
TI  - [The subacromial impingement syndrome].
AB  - The subacromial impingement syndrome describes the pathological contact between
      the rotatory cuff and the acromion. It is only a symptom and not a generic term
      for the different pathological diseases of the subacromial region. It is the
      diagnostical aim to verify the pathogenesis of the impingement syndromes and it
      is essential to differentiate structural versus functional causes. The diagnosis
      "impingement syndrome" should not have an acromioplastic procedure as general
      consequence. Because the expression "impingement syndrome" does not show causal
      approach it should no longer be used as a diagnosis. The term subacromial
      syndrome, in conjunction with the underlying pathological cause, acquires more
      therapeutic and prognostic clarity.

PMID- 16991050
TI  - [Arthroscopic assistance in simultaneous anterior and posterior cruciate ligament
      replacement].

PMID- 16991051
TI  - [Failure after impingement of the first toe joint--an analysis of the common
      causes].

PMID- 16991052
TI  - [The initiative "Skill in the DRK--Berlin I Clinic Westend" of the poet and
      physician Dr. Gottfried Benn on the celebration of his 50th birthday].

PMID- 16991053
TI  - [Periprosthetic fractures in older patients].

PMID- 16991054
TI  - [Results of reconstructive surgery of the anterior cruciate ligament as the
      result of a severe injury].

PMID- 16991055
TI  - [The para-shoulder: lesions of the anterior-superior complex (Labrum, SGHL, SSC)
      and their arthroscopic treatment].

PMID- 16991056
TI  - [Tertiary prevention after osteoporotic fracture--practical implementations in
      the clinical routine as a quality assurance measure].

PMID- 16991057
TI  - [Acute need for action by tissue banks--action guidelines of the German Society
      for Surgery (DGCh) on the background for standards of the tissue extraction and
      processing under the established sanctions of 13 AMG].

PMID- 16991060
TI  - [Frequency and utility of internet use by orthopaedic patients].
AB  - AIM: We assessed to what degree orthopaedic patients use the internet as an
      information platform and how these patients rate the information they obtain over
      the World Wide Web (WWW). METHODS: 450 consecutive patients consulting the out
      patient department of our university clinic for the first time anonymously filled
      out a three-page questionnaire. Apart from clinical and sociodemographic data,
      the questionnaire addressed aspects such as the availability of computers and
      internet. Also, questions concerning the use and interpretation of medical
      information freely available on the WWW were asked. RESULTS: 402 questionnaires
      were evaluated. 54 % of the patients stated that they readily had access to the
      internet. Of the remaining patients without internet access, 19 % planned the
      installation in the near future. The prevalence of the use of the WWW of patients
      in the age group up to 40 years was 72 % and in patients over 40 years only 49 %.
      Compared with internet non-users, internet users were younger (p < 0.001), more
      frequently men (p < 0.05), and of a higher education level (p < 0.001). 68 % used
      the internet on a regular basis with regard to queries concerning their health
      and well being. More than every third patient (38 %) had consulted the internet
      about the specific orthopaedic ailment prior to seeking advice in our clinic.
      Almost half of the patients judged the previous treatment to be partially in
      accordance with the information obtained from the internet. 86 % considered the
      information obtained over the WWW as helpful or very helpful. 85 % would
      recommend other patients to use the internet for information concerning their
      orthopaedic complaint. 65 % of all patients objected to an orthopaedic on-line
      consultation via internet. CONCLUSION: The internet seems to be an important
      source of information for orthopaedic patients. The prevalence concerning the use
      of the WWW is particularly high in younger, well educated patients.

PMID- 16991061
TI  - [Comparative analysis of patient-centered outcome of total hip and knee
      arthroplasty].
AB  - AIM: The aim of the present study was a comparative investigation of the
      functional improvement reported by patients suffering from primary osteoarthritis
      of the knee or hip undergoing total joint replacement and assessed at 3 months.
      METHOD: In a prospective, controlled clinical trial, 56 patients with primary
      osteoarthritis of the hip and 59 patients with primary osteoarthritis of the knee
      undergoing total joint replacement were assessed at two measuring times (day of
      admission = t1 and 3-month follow-up = t2) using the XSMFA-D (Extra Short
      Musculoskeletal Function Assessment Questionnaire--German version), WOMAC
      (Western Ontario and McMasters Universities) arthrosis index and FFb-H OA
      (Function Assessment Questionnaire Hannover Osteoarthritis). The statistical
      analysis included effect sizes as standardised response mean, t-test and
      covariance analysis. RESULTS: Both groups of patients demonstrated significant
      improvements of the musculoskeletal functions measured. The effect sizes between
      baseline scores and 3-month follow-up scores range from 0.4 to 2.0 and can be
      considered as large effects. The covariance analysis showed significant
      differences between patients with osteoarthritis of the hip and knee for almost
      every score examined. Patients with hip replacement showed large improvements. A
      significant influence of the presurgery baseline score on the 3-month score was
      found consistently. Further analysis showed that patients with medium or strong
      degrees of disability according to the Function index of the XSMFA-D showed the
      strongest effects of change at 3 months. However, their scores at t2 were less
      than the scores of the less disabled patients at t1. CONCLUSION: We conclude that
      patients with hip replacement show more improvement 3 months after the surgery
      than patients with knee replacement. Furthermore, it was seen that patients who
      were more disabled before surgery achieved more improvement than the less
      disabled patients. However, they did not achieve the level of the less disabled
      patients. Thus, the recommendation that total joint replacement should be
      performed as late as possible should be reviewed.

PMID- 16991062
TI  - [Simultaneous bilateral total knee arthroplasty in patients with rheumatoid
      arthritis].
AB  - AIM: In the event of destruction of both knee joints, is bilateral total
      arthroplasty a reliable operation that the patient can reasonably be expected to
      undergo? METHOD: In 140 patients [35 men, 105 women, average age 48.6 (range 24
      78) years], a bilateral sequential TEP implantation was performed under one
      anaesthesia session, due to verified destruction of both knee joints (Larsen
      stage III-IV). All patients were treated with a cemented surface replacement
      prosthesis with resurfacing of the patella (Duracon Total Knee System,
      Stryker/Howmedica). Functional assessment was done with the aid of the Lysholm
      score preoperatively as well as 6, 12 and 18 months postoperatively. RESULTS: The
      operation was conducted under one anaesthesia session in all patients. The
      average Lysholm scores improved from 26 (19-45) preoperatively, to 72 (49-81) 6
      months postoperatively, 76 (48-85) 12 months postoperatively and 77 (49-87) 18
      months postoperatively, whereby no significant difference between sides was
      observed. 96% of the patients said that they would undergo the operation again.
      The following complications occurred: 6 prosthesis infections (2.1%), 2 aseptic
      loosenings (0.7%), 8 superficial wound healing disorders (2.9%) and 2 deep vein
      thromboses (0.7%). CONCLUSION: Sequential bilateral total knee arthroplasty under
      one anaesthesia session in patients with rheumatoid arthritis facilitates a much
      quicker rehabilitation, while the overall perioperative risk is not increased.

PMID- 16991063
TI  - [Medium-term results of the cementless femoral neck prosthesis CUT].
AB  - AIM: The present work aims at evaluating the clinical and radiological midterm
      results of the femoral neck prosthesis CUT. METHOD: 67 femoral neck prostheses of
      the type CUT were implanted in 63 patients between 4/1999 and 5/2003 (average age
      56 years). At an average follow-up time of 5.1 years (min.: 2.9; max.: 6.9) 53
      patients with 57 CUT prostheses were examined clinically with the Harris hip
      score and radiologically. All together we determined the state of 64 CUT
      prostheses (96%). RESULTS: The mean Harris hip score improved from 55 points
      preoperatively to 90.4 points at the last follow-up and is assessed as a good
      result. A total of 7 CUT prostheses (11%) had been revised. 3 CUT prostheses
      (4.7%) had been revised because of aseptic loosening, 2 (3.1%) because of
      persisting postoperative thigh pain, 1 (1.6%) because of vertical migration of an
      unsuitable CUT prostheses a few days after the operation and 1 (1.6%) because of
      septic loosening. The survival rate according to Kaplan-Meier was 89.1% at 5.1
      years. If the femoral neck was resected too widely there was an increased rate of
      horizontal migration with aseptic loosening of the CUT prostheses. CONCLUSION: In
      the midterm follow-up the CUT prosthesis shows a higher loosening rate as
      compared with cementless standard stems.

PMID- 16991064
TI  - [Triple pelvic osteotomy (according to Tonnis and Kalchschmidt) in the treatment
      of acetabular dysplasia--medium-term results].
AB  - AIM: The triple pelvic osteotomy according to Tonnis and Kalchschmidt has gained
      major significance in the surgical treatment of acetabular dysplasia in
      adolescents and adults. The curative and prophylactic potentials of this
      operative procedure are reviewed in this study by means of a clinical and
      radiological follow-up trial. METHODS: 34 patients/38 hip joints treated by the
      triple pelvic osteotomy between 1996 and 2005 were reviewed clinically and
      radiologically with an average follow-up of 3.5 years. The radiological
      classification into grades of deviation was done according to Tschauner et al.,
      clinically the preoperative Harris hip score was determined, as well as common
      epidemiologic parameters. At follow-up, the preoperatively determined
      radiological and clinical parameters were controlled and subjected to statistical
      analysis using Student's t-test for the comparison of means between two paired
      groups. Finally, the subjective assessment of the operation's result by the
      patients was registered. RESULTS: A statistically highly significant amelioration
      of the Harris hip score, relevant radiological angles and grades of deviation
      could be demonstrated at follow-up. This fact coincided with a high or very high
      patient satisfaction in 81.7% of the cases. The conversion rate to
      alloarthroplasty was 2.6%. The complication profile was within the scope of
      similar elective hip surgeries. CONCLUSION: The triple pelvic osteotomy according
      to Tonnis and Kalchschmidt has shown in the present study a high and constant
      potential with regard to reduction/absence of disorders as well as a
      statistically highly significant amelioration of clinical scores and relevant
      radiological angles. In our experience, this surgical method can be regarded as
      the joint-preserving method of choice in the cardinal indication of adolescent
      and adult acetabular dysplasia.

PMID- 16991066
TI  - [Treatment of congenital clubfoot with the Ponseti method].
AB  - AIM: The primary therapy for congenital clubfoot is non-surgical involving
      manipulation and serial casting. With traditional casting, relatively large
      numbers of feet require extensive surgery to achieve full correction. The purpose
      of this study was to evaluate the efficacy of the Ponseti method. METHODS:
      Between 1.1.2004 und 31.12.2005, 29 patients with 41 clubfeet were treated with
      the Ponseti method. Only patients without any prior treatment were included.
      Classification followed Pirani's score. The number of casts to full correction,
      tenotomies, number of posteromedial releases, dorsi-, plantarflexion and hindfoot
      position were documented. The follow-up time was 1-9 months, the average follow
      up time was 9.1 months. RESULTS: 39 clubfeet were successfully treated with the
      Ponseti method. The average Pirani score was 4.9. Percutaneous tenotomies were
      necessary in 34 of the clubfeet. Average dorsiflexion was 19 degrees and
      plantarflexion 42 degrees . After failed Ponseti treatment 2 feet were treated
      with a posteromedial release. CONCLUSION: With the Ponseti method the need for
      extensive corrective surgery is greatly reduced. We recommend the Ponseti method
      as standard therapy in clubfoot management.

PMID- 16991065
TI  - [Prediction of the location of the centre of rotation of the hip joint external
      landmarks].
AB  - AIM: The object of this study was to develop a new method to predict the location
      of the centre of rotation of the hip joint reasonably accurately. METHOD: We
      collected the coordinates of palpable bony landmarks in 50 patients, 25 males and
      25 females, using CT scans to predict the physiological location of the centre of
      the hip joint centre. RESULTS: The centre of the hip was located, on average, at
      12% (+/- 2.9) of the inter-ASIS (anterior superior iliac spine) distance medial,
      33% (+/- 3.9) distal and 19% (+/- 2.7) posterior to the anterior superior iliac
      spine (ASIS). CONCLUSION: Knowledge of the physiological centre of rotation of
      the hip may be useful in navigation of the cup in total hip arthroplasty.

PMID- 16991067
TI  - [Retrospective analysis of march fractures in the german armed forces in the
      years 1998 to 2000].
AB  - AIM: The aim of this study was to determine the incidence/frequency of march
      fractures in the German Armed Forces in the years from 1998 to 2000. In
      particular, the age, length of service, distribution of the metatarsals and the
      occurrence of anthropometric risk factors were considered. METHODS: At the
      Medicostatistical Institute of the German Armed Forces the records of soldiers,
      191 cases with 204 fractures, with diagnosed "march fractures" were selected and
      analyzed. RESULTS: 82% of the affected soldiers were between 19 and 22 years old.
      More than 50% of the fractures occurred within the first eight weeks of service.
      In about 64% the 3rd metatarsal was affected, in 25% the 2nd metatarsal and in
      only 11% of all cases the 4th, 5th, and 1st metatarsals. Soldiers were exempted
      from duty for an average of 26.5 days. No specific anthropometric risk factors
      were found to be connected with the occurrence of march fractures. CONCLUSION:
      March fractures in the German Armed Forces are non-predictable injuries of young
      and physically fit individuals; youth is not a protective factor. There is an
      increased risk for march fractures during the first weeks of military service.
      There appears to be no possibility for a screening.

PMID- 16991068
TI  - [Bilateral rupture of the Achilles tendon--an unusual occurrence].
AB  - We present the clinical case of a sixty-four-year-old man with bilateral
      spontaneous rupture of the Achilles tendon having a multiple disseminated
      oesophagus carcinoma. After immobilisation due to metastases of the 2nd lumbar
      vertebra, there was a spontaneous, painless rupture of the Achilles tendon while
      the patient was mobilised wearing a Hohmann spine brace. Afterwards we carried
      out a thorough case history with the help of clinical examination, sonographic
      and magnetic resonance imaging. The bilateral rupture has been treated
      conservatively with the Adipromed Shoe. With regard to the 2nd lumbar vertebra
      fracture and metastases, a Hohmann spine brace was given to the patient. Because
      of the described circumstances, no surgery had been carried out. Furthermore, the
      patient experienced much more independence and an improved quality of life in his
      last couple of months. Surgery would have not been recommended and could have
      caused the complete immobilisation and loss of patient's quality of life. With
      this case report we would like to point out the consequences of an unwise
      therapeutic decision to a patient who only has a few more months to live. This
      case report is discussed with regard to the possible aetiopathology and the
      current literature.

PMID- 16991069
TI  - [Reduction of spondylolisthesis by temporary adjacent segment distraction].
AB  - AIM OF THE STUDY: Multiple instrument systems are currently available for the
      reduction of spondylolisthesis, where posteriorly oriented tensile forces are
      directly acting on the slipped vertebra. The aim of this clinical study was to
      evaluate the clinical efficacy of a new indirect reduction manoeuvre applied to
      the lumbar spine. METHOD: A total number of 32 patients (14 female, 18 male)
      suffering of spondylolisthesis were reduced by transpedicular instrumentation
      during June 2001 until October 2003. The cranial adjacent vertebra was
      temporarily instrumented and the reduction of the slipped vertebra was
      facilitated by the application of traction on the instrumentation leading to
      tension of the longitudinal ligaments. Posterior transforaminal lumbar interbody
      fusion (TLIF) or anterior lumbar interbody fusion (ALIF) was then carried out
      according to the degree of degenerative shortening of the anterior long. spinal
      ligament. On the last follow up (average 32 month postoperatively; min.: 22
      month) both the reduction of the spondylolisthesis and the ossification of the
      interbody fusion was evaluated radiologically. Physical function and patients
      satisfaction was measured by means of the SF 36 questionnaire. RESULTS: The
      dislocation was reduced in all cases (81% on average). At the time of the last
      follow up bony fusion was depicted on the radiographs in all 32 patients. A
      distinct improvement in all categories of the SF 36 (in 5 out of 8 categories
      statistic significant) could be demonstrated. CONCLUSION: Temporary
      intraoperative instrumentation of the cranial adjacent segment proofs to be a
      simple an effective method for the sufficient reduction of spondylolisthesis.

PMID- 16991070
TI  - [Extracorporeal shock-wave lithotripsy for the treatment of calcific tendonitis
      of the glutaeus maximus tendon].
AB  - Calcific tendinitis at the femoral insertion of the glutaeus maximus tendon is an
      unusual but well-described location for an ossifying enthesopathy. Extracorporeal
      shock-wave lithotripsy has become a standard therapy for various pathologies in
      orthopaedics. We report a case of a 50-year-old man with painful calcific
      tendinitis at the femoral insertion of the glutaeus maximus tendon who
      successfully underwent extracorporeal shock-wave treatment.

PMID- 16991071
TI  - [Rotator cuff tear--an occupational disease? An epidemiological analysis].
AB  - BACKGROUND: In literature there are only few data which describe the influence of
      occupation on the development of rotator cuff disease. METHODS: In a
      retrospective study, 760 open rotator cuff repairs were analysed and related to
      the profession and occupational load. Exclusion criteria were traumatic tears and
      sports injuries. All male persons were statistically analysed and the data
      compared with occupational patterns of the region, obtained from the Federal
      Statistical State Office. RESULTS: Rotator cuff repairs were performed in 472
      males who had no evidence for a traumatic origin. After statistical analysis (p <
      0.001) we found significantly more patients working in agriculture and forestry
      (6.38% versus 1.07% in Bavaria) and in the building industry (35.11% versus
      13.40% in Bavaria). CONCLUSIONS: Our data suggest that working exposure increases
      the risk or leads to the clinical manifestation of rotator cuff tears. Although a
      detailed analysis of individual physical exposure is not available yet, the
      statistical results indicate that rotator cuff tears must be taken into
      consideration as a result of ergonomic exposure.

PMID- 16991072
TI  - [An algorithm for reconstruction of soft tissue defects of the distal lower leg,
      ankle and heel].
AB  - AIM: The purpose of the study was to establish an algorithm for the
      reconstruction of soft tissue defects of the distal lower leg, ankle and heel.
      METHOD: 81 patients presenting with soft tissue defects in these regions
      underwent flap coverage. The average age was 44.1 years. Small defects (up to 4 x
      4 cm) were covered by local flaps. The neurovascular sural flap was the
      predominant flap procedure for medium size defects (up to 10 x 15 cm). Free flaps
      were used for larger defects or in cases of stenosis or occlusion of the peroneal
      artery. Femoro-crural bypasses were performed in three cases to improve
      peripheral arterial perfusion. RESULTS: The reconstructive goals were achieved in
      95% of the cases by performing reconstruction according to the established
      algorithm. Minor complications occurred in 29.6% of the cases. CONCLUSION: The
      results appear to be very good considering a patient population with complex and
      predominantly contaminated wounds. A preoperative angiography represents an
      important part of the algorithm for flap reconstruction to detect abnormal
      arterial vascular conditions and thus to plan vascular reconstruction prior to or
      simultaneously with free flap coverage. Additionally, a non-patency of the
      peroneal artery represents a contraindication for sural flaps.

PMID- 16991073
TI  - [Rotationally stable, intramedullary osteosynthesis of proximal extra-articular
      femur fractures].
AB  - AIM: The proximal femur nail (PFN) and the gliding nail (GLN) are two modern
      procedures available for intramedullary osteosynthesis of proximal extra
      articular femur fractures; they allow a rotationally stable fixation of the
      proximal fragment. In a comparative analysis of complications, both methods
      should be evaluated. METHODS: A comparative analysis of both procedures is
      presented in a prospective clinical study design. The treatment of 240
      consecutive patients (124 PFN/116 GLN) with an average follow-up term of 10.2
      months is analysed. RESULTS: Both PFN and GLN give rise to head perforations
      (4.8% and 2.6%), dislocations of material (0.8% and 0%), intraoperative femoral
      shaft fractures (0.8% and 2.6%), pseudarthrosis (0% and 0.9%) and fractures of
      material (0.8% and 0%) in the way of complications as well as wound-healing
      impairments (9.7 % and 5.2 %) and iatrogenic complications such as false
      placement of the osteosynthesis material and errors in reposition (0.8% and
      4.3%). CONCLUSION: The gliding nail osteosynthesis yields a more favourable
      complication profile with regard to specific osteosynthesis-caused complications
      (6.0%) and wound-healing impairments (5.2%) in comparison with the PFN
      osteosynthesis (7.3% and 9.7%, respectively). Especially the cut-out rate of the
      GLN (2.6%) is lower than that of the PFN (4.8%).

PMID- 16991074
TI  - [Systemic spread of wear debris--an in-vivo study].
AB  - AIM: The aim of this study was to elucidate whether there is a systemic spread of
      wear debris from peripherally applied stainless steel and titanium particles into
      the blood and subsequently to parenchymatous organs. Furthermore, we report on
      histological findings at the implantation site. METHOD: In Syrian Gold hamsters
      we implanted 2 mm3 wear debris of stainless steel and titanium into the dorsal
      skin fold chamber. Over a period of 2 weeks we took blood samples and afterwards
      explanted the implant area, the heart, lung, liver and spleen. One half of the
      organs and the implant area were used for histological analysis. The other half
      of the organs and the blood samples were analysed by optical emission
      spectrometer with inductively coupled plasma and graphite furnace atomic
      absorption spectrophotometry for their contents of chromium, nickel and titanium.
      RESULTS: In the group with titanium particles, histological analysis of the
      implant site showed moderate phagocyted wear in granulocytes but no other
      pathological findings. Animals treated with stainless steel wear debris had a
      massive inflammatory reaction, in some cases leading to necrosis. The analysis of
      the blood and one half of the organs showed increased levels of chromium and,
      already 24 hours after implantation, raised values for nickel. The result of the
      hamsters treated with titanium showed significantly elevated levels of titanium
      ions in the organs, but not in the blood samples. Histology of the organs did not
      reveal pathological findings. CONCLUSION: In this study we could show a massive
      inflammatory reaction for stainless steel wear debris in contrast to titanium
      wear debris at the implantation site. The elevated blood levels of chromium and
      increased values of other metals in the organs suggest the haematogenic
      distribution of ions from the peripherally implanted wear debris.

PMID- 16991075
TI  - Influenza vaccination of children: Can it be accomplished?

PMID- 16991076
TI  - Poor specific T cell responses to human herpesvirus 8: A key to unleashing Kaposi
      sarcoma?

PMID- 16991077
TI  - Immunogenicity and reactogenicity of 1 versus 2 doses of trivalent inactivated
      influenza vaccine in vaccine-naive 5-8-year-old children.
AB  - BACKGROUND: Two doses of trivalent inactivated influenza vaccine (TIV) are
      recommended for children <9 years old receiving vaccine for the first time, but
      compliance is suboptimal. This study assessed the need for a second dose of TIV
      in this age group. METHODS: In this prospective, open-label study, 232 influenza
      vaccine-naive 5-8-year-olds enrolled in a health maintenance organization
      received 2 doses of TIV in fall 2004. Serum for antibody titer measurement was
      obtained at 3 time points (n = 222). Parents completed diaries for 5 days.
      RESULTS: Both doses of vaccine were well tolerated. The strongest predictor of a
      protective antibody response (> or =1 : 40) after 1 dose of TIV was baseline
      seropositive status. In multivariate analysis adjusting for age, sex, and
      baseline serostatus, the proportion of children with protective antibody
      responses was significantly higher after 2 doses than after 1 dose of TIV for
      each antigen (P < .001, for A/H1N1; P = .01, for A/H3N2; P < .001, for B). Age
      and sex were not independently predictive of a protective antibody response. Over
      one-third of children had antibody responses <1:40 for the type B vaccine
      component, even after 2 doses. CONCLUSIONS: The present study supports the need
      for 2 doses of TIV in 5-8-year-olds receiving TIV for the first time. Efforts to
      increase compliance with the 2-dose recommendation are warranted.

PMID- 16991078
TI  - Cross-protectiveness and immunogenicity of influenza A/Duck/Singapore/3/97(H5)
      vaccines against infection with A/Vietnam/1203/04(H5N1) virus in ferrets.
AB  - Ferrets were immunized with two 7- mu g doses of hemagglutinin from inactivated
      whole-virus vaccines containing the hemagglutinin gene of
      A/Duck/Singapore/3/97(H5N3) then inoculated with a lethal dose of
      A/Vietnam/1203/04(H5N1) (Viet/1203/04). Serum samples did not react with
      Viet/1203/04 in hemagglutination-inhibition (HI) or virus-neutralization (VN)
      tests. All vaccinated ferrets survived the challenge, whereas all mock-immunized
      ferrets died. Immunized ferrets had significantly lower virus titers in the upper
      respiratory tract and less-severe disease. Vaccine generated from antigenically
      different H5 virus protects against infection by a highly pathogenic H5 strain.
      Neither HI nor VN testing provides correlates of cross-protection in ferrets.

PMID- 16991079
TI  - Prevalence of HPV infection among men: A systematic review of the literature.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is estimated to be the most
      common sexually transmitted infection; an estimated 6.2 million persons are newly
      infected every year in the United States. There are limited data on HPV infection
      in heterosexual men. METHODS: We conducted a systematic review of the literature
      by searching MEDLINE using the terms "human papillomavirus," "HPV," "male,"
      "seroprevalence," and "serology" to retrieve articles published from 1 January
      1990 to 1 February 2006. We included studies that had data on population
      characteristics and that evaluated male genital anatomic sites or specimens for
      HPV DNA or included assessments of seropositivity to HPV type 6, 11, 16, or 18 in
      men. We excluded studies that had been conducted only in children or
      immunocompromised persons (HIV infected, transplant recipients, or elderly).
      RESULTS: We included a total of 40 publications on HPV DNA detection and risk
      factors for HPV in men; 27 evaluated multiple anatomic sites or specimens, 10
      evaluated a single site or specimen, and 3 evaluated risk factors or optimal
      anatomic sites/specimens for HPV detection. Twelve studies assessed site- or
      specimen-specific HPV DNA detection. HPV prevalence in men was 1.3%-72.9% in
      studies in which multiple anatomic sites or specimens were evaluated; 15 (56%) of
      these studies reported > or =20% HPV prevalence. HPV prevalence varied on the
      basis of sampling, processing methods, and the anatomic site(s) or specimen(s)
      sampled. We included 15 publications reporting HPV seroprevalence. Rates of
      seropositivity depended on the population, HPV type, and methods used. In 9
      studies that evaluated both men and women, all but 1 demonstrated that HPV
      seroprevalence was lower in men than in women. CONCLUSION: HPV infection is
      highly prevalent in sexually active men and can be detected by use of a variety
      of specimens and methods. There have been few natural-history studies and no
      transmission studies of HPV in men. The information that we have reviewed may be
      useful for future natural-history studies and for modeling the potential impact
      of a prophylactic HPV vaccine.

PMID- 16991080
TI  - In vitro interaction between hepatitis C virus (HCV) envelope glycoprotein E2 and
      serum lipoproteins (LPs) results in enhanced cellular binding of both HCV E2 and
      LPs.
AB  - Hepatitis C virus (HCV) particles in serum associate with lipoproteins (LPs), and
      the low-density lipoprotein receptor (LDLr) has been implicated in virus
      attachment and entry into cells. To clarify the basis of interactions between
      virus and LPs, we determined whether HCV interacts with human LPs via its
      envelope glycoprotein E2. The binding of serum-derived virus-like particles, HCV
      E2, and HCV E2-LP complexes to CD81 and LDLr was studied. Incubation of HCV E2
      protein with human and bovine LPs (very low density, low density, and high
      density) enhanced the binding of both HCV E2 and LPs to CD4+ lymphoblastoid (MOLT
      4) cells, foreskin fibroblasts, and hepatocytes. The binding of HCV E2 to MOLT-4
      cells was not enhanced when it was preincubated with lipid-free apoprotein B,
      which suggests that E2 interacts with the lipid moiety of human lipoproteins. The
      LP interaction was specific for HCV E2--incubation of HIV gp120 with LPs did not
      enhance gp120 binding to MOLT-4 cells. The enhanced HCV E2 binding required
      expression of both human CD81 and LDLr. These data suggest that HCV E2 associates
      with LDL and that the resulting complex enhances binding of both ligands to
      cells, which may contribute to the finding that HCV-infected individuals have
      significantly lower levels of LDL than control subjects.

PMID- 16991081
TI  - Phenotypic and functional status of intrahepatic T cells in chronic hepatitis C.
AB  - Polychromatic flow-cytometric assays were used to analyze paired intrahepatic and
      peripheral lymphocyte samples from 37 patients with chronic hepatitis C. Compared
      with peripheral cells, intrahepatic T cells were selectively enriched with
      CD45RO+ memory T cells but had a lower percentage of CD4+ T cells expressing the
      differentiation markers CD27 and CD28. The percentage of intrahepatic CD45RO+ and
      CD28+ T cells correlated with the degree of liver inflammation, which suggests
      that memory T cells at relatively early stages of differentiation are directly
      involved in liver inflammation. Despite their memory phenotype, intrahepatic T
      cells were defective in proliferation capability, produced less interferon- gamma
      in response to stimulation by T cell receptor, and contained less perforin but
      expressed higher levels of Fas and Fas ligand, compared with their counterparts
      in peripheral blood. The distinct characteristics of intrahepatic T cells suggest
      that they play an important role in the immunopathogenesis of chronic hepatitis
      C.

PMID- 16991082
TI  - Low T cell responses to human herpesvirus 8 in patients with AIDS-related and
      classic Kaposi sarcoma.
AB  - BACKGROUND: Kaposi sarcoma (KS) occurs mainly in immunocompromised patients and
      is strongly associated with infection with human herpesvirus 8 (HHV-8; also known
      as "KS-associated herpesvirus"). We hypothesized that KS is linked to
      deficiencies in specific anti-HHV-8 T cell immunity. METHODS: We studied
      asymptomatic HHV-8 carriers coinfected with human immunodeficiency virus (HIV; n
      = 23) and patients with HIV-related or classic KS (n = 29). We used an interferon
      gamma enzyme-linked immunospot assay with 56 specific peptides distributed on 6
      HHV-8 proteins (glycoprotein [gp] B, gpH, gp35/37, latent nuclear antigen 1 [LANA
      1], K12, and K15) to detect HHV-8-specific T cell responses. RESULTS: We found
      that patients with KS responded to these peptides less often and had much lower
      HHV-8-specific T cells counts than did asymptomatic HHV-8 carriers (P = .001 and
      P = .0004, respectively), regardless of CD4 T cell count or HHV-8 load. The
      frequency of Epstein-Barr virus-specific T cells was similar in both groups.
      CONCLUSIONS: Our results suggest that HIV-related and classic KS are associated
      with a lack of HHV-8-specific T cells. Also, we have described 8 new HHV-8 T cell
      epitopes in LANA-1, K12, and K15, including 2 CD4 T cell epitopes. These data
      provide new insight into HHV-8 cellular immunity.

PMID- 16991083
TI  - Effect of perinatal antiretroviral drug exposure on hematologic values in HIV
      uninfected children: An analysis of the women and infants transmission study.
AB  - BACKGROUND: With the increasing use of antiretroviral (ARV) drugs to prevent
      mother-to-child transmission of human immunodeficiency virus (HIV), large numbers
      of infants are exposed, with possible consequent toxicity. METHODS: Hematologic
      values in 1820 uninfected HIV- and ARV-exposed children were compared with those
      in 351 ARV-unexposed children from the Women and Infants Transmission Study.
      Hemoglobin concentrations and platelet, neutrophil, lymphocyte, and CD4+ and CD8+
      cell counts were analyzed at birth and ages 2, 6, 12, 18, and 24 months.
      Multivariate analysis was conducted age 0-2 and 6-24 months, with adjustment for
      multiple cofactors. RESULTS: Hemoglobin concentrations and neutrophil,
      lymphocyte, and CD4+ cell counts were significantly lower at age 0-2 months in
      infants exposed to ARV drugs than in those who were not. At 6-24 months,
      differences in hemoglobin concentrations and neutrophil counts were no longer
      significant, whereas differences in platelet, lymphocyte, and CD4+ cell counts
      persisted and CD8+ cell counts became significantly lower. In comparison with ARV
      monotherapy, combination therapy was associated with larger decreases in
      neutrophil, lymphocyte, and CD8+ cell counts at age 0-2 months but with only
      differences in CD8+ cell counts at age 6-24 months. Clinically significant
      abnormalities were rare and did not differ by exposure to ARV drugs. CONCLUSION:
      Infants exposed to ARV drugs have small but significant differences in several
      hematologic parameters for the first 24 months of life. These results indicate
      the need for long-term follow-up of uninfected infants with ARV exposure.

PMID- 16991084
TI  - Immunogenetics of CD4 lymphocyte count recovery during antiretroviral therapy: An
      AIDS Clinical Trials Group study.
AB  - During antiretroviral therapy, CD4 lymphocyte count increases are modest in some
      patients despite virologic control. We explored whether polymorphisms in genes
      important for T cell expansion, survival, and apoptosis are associated with the
      magnitude of CD4 lymphocyte count recovery during antiretroviral therapy. We
      studied treatment-naive individuals who achieved sustained control of plasma
      viremia (<400 HIV-1 RNA copies/mL) for at least 48 weeks after initiation of
      antiretroviral therapy and compared genotypes among individuals who had an
      increase of either <200 or > or =200 CD4 cells/mm3 from baseline. A total of 137
      single-nucleotide polymorphisms across 17 genes were characterized in 873 study
      participants. In multivariate analyses that controlled for clinical variables,
      polymorphisms in genes encoding tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL), TNF- alpha , Bcl-2-interacting molecule (Bim),
      interleukin (IL)-15, and IL-15 receptor alpha chain (IL-15R alpha ) were
      associated with the magnitude of the increase in CD4 lymphocyte count, as were
      haplotypes in genes encoding interferon- alpha , IL-2, and IL-15R alpha (P < .05,
      for each). Multifactor dimensionality reduction identified a gene-gene
      interaction between IL-2/IL-15 receptor common beta chain and IL-2/IL-7/IL-15
      receptor common gamma chain. Immune recovery during antiretroviral therapy is a
      complex phenotype that is influenced by multiple genetic variants. Future studies
      should validate these tentative associations and define underlying mechanisms.

PMID- 16991085
TI  - A simple, dynamic measure of antiretroviral therapy adherence predicts failure to
      maintain HIV-1 suppression.
AB  - BACKGROUND: High levels of antiretroviral therapy adherence are important for
      human immunodeficiency virus type 1 (HIV-1) suppression, yet the magnitude of
      adherence required to maintain it is less well characterized. Furthermore,
      methods to accommodate changes in adherence over time are lacking. In the present
      study, our objective was to determine the magnitude of antiretroviral therapy
      adherence needed to maintain HIV-1 suppression by use of a time-updated adherence
      measure that has the potential to be of use in a clinical setting. METHODS: We
      examined a population-based cohort of HIV-1-infected subjects > or =18 years of
      age, residing in British Columbia, Canada, who started receiving antiretroviral
      therapy between 1 August 1996 and 30 September 2003, who had at least 2
      consecutive viral loads <500 copies/mL and who had prescriptions filled at least
      3 times during a follow-up period ending 30 September 2004. Virological failure
      was defined as the second of 2 consecutive viral loads >1000 copies/mL. Cox
      proportional hazards model was used to determine the relationship between
      virological failure and refill-based, time-updated surrogate measure of
      adherence. RESULTS: Among the 1634 participants > or =18 years of age who
      initiated triple combination therapy during the study, 606 virological failure
      events were identified. In multivariate analyses, subjects with < or =95%
      adherence were 1.66 (95% confidence interval, 1.38-2.01) times more likely to
      experience virological failure than those with >95% adherence. CONCLUSIONS: The
      highest levels of antiretroviral therapy adherence are associated with higher
      rates of maintained virological suppression. This simple, dynamic surrogate
      measure of adherence overcomes the limitation of single-point-in-time
      calculations of adherence and may be useful in real time to determine whether an
      individual is exhibiting incomplete adherence.

PMID- 16991086
TI  - High incidence of genotypic variance between sequential herpes simplex virus type
      2 isolates from HIV-1-seropositive patients with recurrent genital herpes.
AB  - We developed a polymerase chain reaction (PCR) method, based on strain-to-strain
      variation of DNA repeats in the herpes simplex virus type 2 (HSV-2) genes US1 and
      US12, to genotype HSV-2 strains and determine the incidence and risk factors
      associated with HSV-2 superinfection in patients with recurrent genital herpes
      (RGH). Forty-seven (92%) of 51 unrelated HSV-2 isolates could be distinguished.
      Genotyping of sequential HSV-2 isolates showed a different genotype in all of the
      11 human immunodeficiency virus type 1 (HIV-1)-seropositive patients with RGH,
      compared with 1 of the 8 HIV-1-seronegative patients with RGH. The PCR approach
      developed distinguishes unrelated HSV-2 strains efficiently and indicated a high
      incidence of genotype variance between sequential HSV-2 isolates of HIV-1
      seropositive patients with RGH.

PMID- 16991087
TI  - "Gesundheit!" sneezing, common colds, allergies, and Staphylococcus aureus
      dispersion.
AB  - BACKGROUND: Staphylococcus aureus is among the most important pathogens in
      today's hospital setting. METHODS: The effects of sneezing on the airborne
      dispersal of S. aureus and other bacteria were assessed in 11 healthy nasal S.
      aureus carriers with experimentally induced rhinovirus colds. Airborne dispersal
      was studied by volumetric air sampling in 2 chamber sessions with and without
      histamine-induced sneezing. After 2 days of preexposure measurements, volunteers
      were inoculated with a rhinovirus and monitored for 14 days. Daily quantitative
      nasal- and skin-culture samples for bacteria and nasal-culture samples for
      rhinovirus were obtained, cold symptoms were assessed, and volunteer activities
      were recorded during sessions. RESULTS: All participants developed a cold.
      Sneezing caused a 4.7-fold increase in the airborne dispersal of S. aureus, a 1.4
      fold increase in coagulase-negative staphylococci (CoNS), and a 3.9-fold increase
      in other bacteria (P < .001). An additional 2.83 colony forming units (cfu) of S.
      aureus/m3/min, 3.24 cfu of CoNS/m3/min, and 474.61 cfu of other bacteria/m3/min
      were released per sneeze. Rhinovirus exposure did not change the frequency of
      sneezing or airborne dispersal. Having respiratory allergies increased the spread
      of S. aureus by 3.8-fold during sneezing sessions (P < .001). CONCLUSION: Nasal
      S. aureus carriers disperse a significant amount of S. aureus into the air by
      sneezing. Experimental colds do not alter bacterial dispersal, but respiratory
      allergies multiply the effect of dispersing S. aureus.

PMID- 16991088
TI  - A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein
      is associated with susceptibility to meningeal tuberculosis.
AB  - BACKGROUND: Although meningitis is the most severe form of infection caused by
      Mycobacterium tuberculosis, the immunopathogenesis of this disease is poorly
      understood. We tested the hypothesis that polymorphisms in Toll-interleukin 1
      receptor domain containing adaptor protein (TIRAP), an adaptor protein that
      mediates signals from Toll-like receptors activated by mycobacteria, are
      associated with susceptibility to tuberculosis (TB). METHODS: We used a case
      population study design in Vietnam with cord-blood control samples (n = 392) and
      case patients (n = 358) who had either pulmonary (n = 183) or meningeal (n = 175)
      TB. RESULTS: The TIRAP single-nucleotide polymorphism (SNP) C558T was associated
      with increased susceptibility to TB, with a 558T allele frequency of 0.035 in
      control samples versus 0.074 in case patients (odds ratio [OR], 2.25; P < .001).
      Subgroup analysis revealed that SNP 558T was more strongly associated with
      susceptibility to meningeal TB (OR, 3.02; P < .001) than to pulmonary TB (OR,
      1.55; P = .22). In comparison to the 558CC genotype, the 558TT genotype was
      associated with decreased whole-blood interleukin-6 production, which suggests
      that TIRAP influences disease susceptibility by modulating the inflammatory
      response. CONCLUSIONS: These results provide the first evidence of an association
      of a TIRAP SNP with the risk of any disease and also suggest that the Toll-like
      receptor pathway influences susceptibility to meningeal and pulmonary TB by
      different immune mechanisms.

PMID- 16991089
TI  - Fabry disease in mice protects against lethal disease caused by Shiga toxin
      expressing enterohemorrhagic Escherichia coli.
AB  - Fabry disease is an X-linked recessive disorder in which affected persons lack
      alpha-galactosidase A (alpha -GalA), which leads to excess glycosphingolipids in
      tissues, mainly globotriaosylceramide (Gb3). Gb3 is the cellular receptor for
      Shiga toxin (Stx), the primary virulence factor of enterohemorrhagic Escherichia
      coli. alpha-GalA-knockout mice were significantly protected against lethal
      intraperitoneal doses of Stx2 or oral doses of Stx2-expressing bacteria, compared
      with wild-type (wt) control mice. Kidneys of moribund wt mice revealed tubular
      necrosis, but no histopathologic changes were observed in Gb3-overexpressing
      mice. Reducing Gb3 levels in alpha-GalA-knockout mice by the intravenous
      injection of recombinant human alpha-GalA restored the susceptibility of knockout
      mice to lethal doses of Stx2. These results suggest that excess amounts of Gb3 in
      alpha-GalA-deficient mice may impair toxin delivery to susceptible tissues.

PMID- 16991090
TI  - Experimental mouse lethality of Escherichia coli isolates, in relation to
      accessory traits, phylogenetic group, and ecological source.
AB  - BACKGROUND: Whether accessory traits, phylogenetic background, or ecological
      source best predicts extraintestinal virulence within Escherichia coli is
      undefined. METHODS: A total of 90 E. coli strains (18 fecal isolates and 72
      extraintestinal-infection isolates) were characterized for 55 accessory traits
      and phylogenetic group (A, B1, B2, or D). Bacterial traits and ecological source
      were compared with experimental mouse lethality. RESULTS: Of the 90 strains, 41%
      were "killers" (i.e., killed > or =90% of mice). By univariate analysis, multiple
      group B2-associated traits (including malX [pathogenicity-island marker], pap [P
      fimbriae] elements, usp [uropathogenic-specific protein], and fyuA
      [yersiniabactin system]) were most closely associated with killer status,
      followed by group B2 (or non-group A) status and then by nonfecal origin.
      Stepwise multivariate analysis identified pap, malX, usp, fyuA, and B2 (all of
      which were positive predictors) and ireA (which was a negative predictor) as
      significant predictors of killer status. Killer strains segregated significantly
      from nonkiller strains, according to accessory-trait profiles. Factorial analysis
      of correspondence placed group B2 among the traits most closely associated with
      killer status, but not as the closest. CONCLUSIONS: Specific group B2-associated
      accessory traits are more potent predictors of experimental virulence among E.
      coli isolates than is either phylogenetic background or ecological source.
      Molecular typing can estimate an E. coli isolate's extraintestinal virulence
      potential, regardless of source.

PMID- 16991091
TI  - Immunotherapy for drug-refractory mucosal leishmaniasis.
AB  - BACKGROUND: Pentavalent antimony (Sb(v)) is the mainstay therapy for mucosal
      leishmaniasis (ML), but it is toxic, and relapses are common. Immunotherapy using
      a mixture of killed parasites, with or without bacille Calmette-Guerin, is an
      alternative but is used sporadically because of inconsistent results. METHODS: We
      developed a defined immunotherapeutic antigen preparation for use in an
      observational, open-label trial to treat 6 patients with ML with a history of
      Sb(v) therapy failure. All patients were treated with the antigens thiol-specific
      antioxidant, Leishmania major stress inducible protein 1, Leishmania elongation
      initiation factor, and Leishmania heat shock protein 83, plus granulocyte
      macrophage colony-stimulating factor. Patients underwent clinical and
      pathological evaluations before the initiation of immunotherapy and at 3, 6, 9,
      12, 18, 24, and 60 months after. RESULTS: One month after the third injection, 1
      patient showed complete clinical remission (CC) and remained disease free for the
      duration of the study. At the 9-month follow-up examination, 5 patients showed
      CC, and all patients were asymptomatic at a subsequent 5-year follow-up
      examination. CONCLUSIONS: These data support the concept that vaccine therapy
      with a defined antigen combination, used with standard chemotherapy, is a safe
      and effective approach to treat drug-refractory ML.

PMID- 16991092
TI  - Resistance to oxidative stress is associated with metastasis in mucocutaneous
      leishmaniasis.
AB  - Mucocutaneous leishmaniasis (MCL) in South and Central America is characterized
      by the dissemination (metastasis) of Leishmania Viannia subgenus parasites from a
      cutaneous lesion to nasopharyngeal tissues. Little is known about the
      pathogenesis of MCL, especially with regard to the virulence of the parasites and
      the process of metastatic dissemination. We previously examined the functional
      relationship between cytoplasmic peroxiredoxin and metastatic phenotype using
      highly, infrequently, and nonmetastatic clones isolated from an L. (V.)
      guyanensis strain previously shown to be highly metastatic in golden hamsters.
      Distinct forms of cytoplasmic peroxiredoxin were identified and found to be
      associated with the metastatic phenotype. We report here that peroxidase activity
      in the presence of hydrogen peroxide and infectivity differs between metastatic
      and nonmetastatic L. (V.) guyanensis clones. After hydrogen peroxide treatment or
      heat shock, peroxiredoxin was detected preferentially as dimers in metastatic L.
      (V.) guyanensis clones and in L. (V.) panamensis strains from patients with MCL,
      compared with nonmetastatic parasites. These data provide evidence that
      resistance to the first microbicidal response of the host cell by Leishmania
      promastigotes is linked to peroxiredoxin conformation and may be relevant to
      intracellular survival and persistence, which are prerequisites for the
      development of metastatic disease.

PMID- 16991093
TI  - American tegumentary leishmaniasis: Is antimonial treatment outcome related to
      parasite drug susceptibility?
AB  - BACKGROUND: Antimonials are the first drug of choice for the treatment of
      American tegumentary leishmaniasis (ATL); however, their efficacy is not
      predictable, and this may be linked to parasite drug resistance. We aimed to
      characterize the in vitro antimony susceptibility of clinical isolates of
      Peruvian patients with ATL who were treated with sodium stibogluconate and to
      correlate this in vitro phenotype with different treatment outcomes. METHODS:
      Thirty-seven clinical isolates were obtained from patients with known disease and
      treatment histories. These isolates were typed, and the susceptibility of
      intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials
      was determined. RESULTS: We observed 29 SbV-resistant isolates among 4 species of
      subgenus Viannia, most of which exhibited primary resistance; isolates resistant
      only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive
      to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant
      to SbV only (the majority of isolates fell into this category). There was no
      correlation between in vitro susceptibility to both antimonials and the clinical
      outcome of therapy. CONCLUSION: Antimony insensitivity might occur in a stepwise
      fashion (first to SbV and then to SbIII). Our data question the definition of
      true parasite resistance to antimonials. Further studies of treatment efficacy
      should apply standardized protocols and definitions and should also consider host
      factors.

PMID- 16991094
TI  - Mic1-3 knockout of Toxoplasma gondii is a successful vaccine against chronic and
      congenital toxoplasmosis in mice.
AB  - BACKGROUND: We evaluated a new vaccine, Mic1-3KO, against both chronic and
      congenital toxoplasmosis in mice. Mic1-3KO is a mutant strain of Toxoplasma
      gondii RH that lacks the mic1 and mic3 genes. METHODS: OF1 mice were vaccinated
      with Mic1-3KO tachyzoites and challenged orally with T. gondii (strain 76K).
      Immune responses and protection against chronic infection (cyst load in brain
      tissue) and congenital infection (maternofetal transmission, survival, body
      weight, and chronic infection in pups) were evaluated. RESULTS: Mic1-3KO induced
      a strong humoral and cellular T helper (Th) 1 response and conferred highly
      significant protection against chronic infection (>96% reduction in cysts in
      brain tissue). Fewer infected fetuses were observed in vaccinated dams that were
      infected during pregnancy than in nonvaccinated infected dams (4.6% vs. 33.3%).
      All pups born to vaccinated infected dams survived and had the same weight as
      those born to nonvaccinated uninfected dams. Furthermore, they had significantly
      fewer cysts in brain tissue (>91%) than pups from nonvaccinated infected dams.
      During pregnancy, protection against congenital disease was associated with a
      cellular Th1 response regulated by interleukin-10. One month after delivery,
      vaccinated infected dams had >96% fewer cysts in their brain tissue than
      nonvaccinated infected dams. CONCLUSION: Mic1-3KO is an effective vaccine against
      chronic and congenital toxoplasmosis.

PMID- 16991095
TI  - DC-SIGNR neck-region polymorphisms and HIV-1 susceptibility: From population
      stratification to a possible advantage of the 7/5 heterozygous genotype.

PMID- 16991098
TI  - On the impact of HIV-associated immunosuppression and malaria infection in
      Malawi.

PMID- 16991100
TI  - Nitric oxide, a double edged sword in cancer biology: searching for therapeutic
      opportunities.
AB  - Nitric oxide (NO) is a pleiotropic molecule critical to a number of physiological
      and pathological processes. The last decade has witnessed major advances in
      dissecting NO biology and its role in cancer pathogenesis. However, the
      complexity of the interactions between different levels of NO and several aspects
      of tumor development/progression has led to apparently conflicting findings.
      Furthermore, both anti-NO and NO-based anticancer strategies appear effective in
      several preclinical models. This paradoxical dichotomy is leaving investigators
      with a double challenge: to determine the net impact of NO on cancer behavior and
      to define the therapeutic role of NO-centered anticancer strategies. Only a
      comprehensive and dynamic view of the cascade of molecular and cellular events
      underlying tumor biology and affected by NO will allow investigators to exploit
      the potential antitumor properties of drugs interfering with NO metabolism.
      Available data suggest that NO should be considered neither a universal target
      nor a magic bullet, but rather a signal transducer to be modulated according to
      the molecular makeup of each individual cancer and the interplay with
      conventional antineoplastic agents.

PMID- 16991101
TI  - On the formation of [H3C-S-S-CH3]+* ions from the bis(dimethylthio)mercury
      molecular ion.

PMID- 16991102
TI  - Instrument dependence of electrospray ionization and tandem mass spectrometric
      fragmentation of the gingerols.
AB  - The gingerols, including [6]-, [8]-, and [10]-gingerols, a series of chemical
      homologs differentiated by the length of their unbranched alkyl chains, have been
      identified as major active components in fresh ginger rhizome. The purpose of
      this study was to investigate the utility of ion trap liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) as an online tool to identify
      and quantify these compounds in raw or processed ginger rhizome samples. Negative
      mode electrospray ionization (ESI) was used in MS, MS/MS and MS(n) experiments in
      quadrupole ion trap instruments from two different manufacturers and in high
      resolution and accurate mass MS and MS/MS experiments in a Fourier transform ion
      cyclotron resonance mass spectrometer to elucidate the ionization and
      fragmentation mechanisms of these compounds in these instruments. Positive mode
      ESI, which generated many more fragment ions in full scan MS even under gentle
      ionization conditions, was also used in LC/MS and MS/MS experiments and in direct
      infusion MS and MS/MS experiments. Consistent and predictable ionization and
      fragmentation behaviors were observed for all gingerols when analyzed in the same
      instrument. Instruments from different manufacturers, however, had different
      ionization mechanisms. The major difference between instruments was their ability
      to form covalent dimer adducts of the gingerols. Subsequent fragmentation
      patterns of the precursor ions were essentially identical. These results clearly
      demonstrate that LC/MS instruments produce data that cannot necessarily be
      replicated in other laboratories, especially if those laboratories do not have
      the same instrument model from the same manufacturer. This presents major
      problems for metabolite target analysis, metabolic profiling and metabolomics
      investigations, which would benefit from LC/MS mass spectrum libraries as they do
      from GC/MS mass spectrum libraries, because such libraries may not be valid
      across platforms.

PMID- 16991103
TI  - Application of liquid chromatography/ion trap mass spectrometry to the
      characterization of the related substances of clarithromycin.
AB  - A selective reversed-phase liquid chromatography/mass spectrometry (LC/MS(n))
      method was developed for the characterization of components of the semi-synthetic
      macrolide clarithromycin. Mass spectral data were acquired online on a LCQ ion
      trap mass spectrometer equipped with an electrospray ionization source operated
      in the positive ion mode. One unknown compound was structurally elucidated and
      two other unknowns were characterized using the MS/MS and MS(n) collision-induced
      dissociation spectra of reference substances as interpretative templates,
      combined with knowledge of the nature of functional group fragmentation
      behaviour. Given the importance attached to the identification of impurities of
      unknown identity in pharmaceutical substances, this study is useful for companies
      producing clarithromycin.

PMID- 16991104
TI  - A simulation study comparing properties of heterogeneity measures in meta
      analyses.
AB  - The assessment of heterogeneity or between-study variance is an important issue
      in meta-analysis. It determines the statistical methods to be used and the
      interpretation of the results. Tests of heterogeneity may be misleading either
      due to low power for sparse data or to the detection of irrelevant amounts of
      heterogeneity when many studies are involved. In the former case, notable
      heterogeneity may remain unconsidered and an unsuitable model may be chosen and
      the latter case may lead to unnecessary complex analyses strategies. Measures of
      heterogeneity are better suited to determine appropriate analyses strategies. We
      review two measures with different scaling and compare them with the
      heterogeneity test. Estimates of the within-study variance are discussed and a
      new total information measure is introduced. Various properties of the quantities
      in question are assessed by a simulation study. Heterogeneity test and measures
      are not directly related to the amount of between-study variance but to the
      relative increase of variance due to heterogeneity. It is more favourable to base
      the within-study variance estimate on the squared weights of individual studies
      than on the sum of weights. A heterogeneity measure scaled to a fixed interval
      needs reference values for proper interpretation. A measure defined by the
      relation of between- to within-study variance has a more natural interpretation
      but no upper limit. Both measures are quantifications of the impact of
      heterogeneity on the meta-analysis result as both depend on the variance of the
      individual study effects and thus on the number of patients in the studies.

PMID- 16991105
TI  - Seasonal confounding in air pollution and health time-series studies: effect on
      air pollution effect estimates.
AB  - A major statistical challenge in air pollution and health time-series studies is
      to adequately control for confounding effects of time-varying covariates. Daily
      health outcome counts are most commonly analysed by Poisson regression models,
      adjusted for overdispersion, with air pollution levels included as a linear
      predictor and smooth functions for calendar time and weather variables to adjust
      for time-varying confounders. Various smoothers have been used so far, but the
      optimal strategy for choosing smoothers and their degree of smoothing remains
      controversial. In this work, we evaluate the performance of various smoothers
      with different criteria for choosing the degree of smoothing in terms of bias and
      efficiency of the air pollution effect estimate in a simulation study. The
      evaluated approaches were also applied to real mortality data from 22 European
      cities. The simulation study imitated a multi-city study. Data were generated
      from a fully parametric model. Model selection methods which optimize prediction
      may lead to increased biases in the air pollution effect estimate. Minimization
      of the absolute value of the sum of the partial autocorrelation function of the
      model's residuals (PACF), as a criterion to choose the degree of smoothness, gave
      the smallest biases. The penalized splines (PS) method with a large number of
      effective dfs (e.g. 8-12 per year) could be used as the basic, relatively
      conservative, analysis whereas the PS and natural splines in combination with
      PACF could be applied to provide a reasonable range of the effect estimate.

PMID- 16991106
TI  - Brief cognitive assessment of cancer patients: evaluation of the Mini-Mental
      State Examination (MMSE) psychometric properties.
AB  - AIM: The aim of the present study was to validate the Greek version of the MMSE
      in advanced-cancer patients attending a palliative care unit. METHODS: The sample
      consisted of 103 advanced-cancer patients. The questionnaire was completed at
      baseline and three days later. Together with the MMSE, the patients also
      completed the EORTC QLQ-C30 Cognitive functioning scale, while researchers
      recorded data on demographic characteristics, disease status and treatment
      regimen. RESULTS: MMSE had overall Cronbach alpha 0.890. Validity as performed
      using known-group analysis showed good results. MMSE discriminated well between
      subgroups of patients differing in disease severity as defined by ECOG
      performance status. Comparison between the MMSE and the EORTC Cognitive
      functioning scale was statistically significant (p<0.05). CONCLUSION: These
      psychometric properties of the Greek version of the MMSE confirm it as a valid
      and reliable measure when administered to patients with advanced cancer.

PMID- 16991107
TI  - Impact of providing audiotapes of primary treatment consultations to men with
      prostate cancer: a multi-site, randomized, controlled trial.
AB  - BACKGROUND: The purpose of this investigation was to systematically examine the
      efficacy of providing men with prostate cancer with an audiotape of their primary
      treatment consultation. METHOD: Participants included 425 men newly diagnosed
      with prostate cancer and 15 radiation oncologists from 4 cancer centers in
      Canada. Patients were block randomized to one of four consultation groups: 1.
      Standard care control--not audio-taped; 2. Audio-taped--no audiotape given; 3.
      Audio-taped--patient given audiotape; and 4. Audio-taped--patient offered choice
      of receiving audiotape or not (4 patients declined; 94 accepted). Patient
      outcomes were measured at 12 weeks post-consultation: perceived degree of
      information provision; audiotape satisfaction and use; communication satisfaction
      with oncologist; mood state; and cancer-specific quality of life. RESULTS:
      Patients receiving the consultation audiotape reported having been provided with
      significantly more disease and treatment information in general (p=0.04), and
      more information about treatment alternatives (p=0.04) and treatment side effects
      (p=0.01) in particular, than patients who did not receive the audiotape.
      Audiotape benefit was not significantly related to patient satisfaction with
      communication, mood state or quality of life at 12 weeks post-consultation, and
      was not significantly affected by choice of receiving the audiotape. Patients
      rated the audiotape intervention positively, with an average score of 83.0 out of
      100. CONCLUSION: Consultation audiotapes are rated highly by men with prostate
      cancer, and these audiotapes help to enhance their perception of having been
      provided with critical disease- and treatment-related information.

PMID- 16991108
TI  - Simplification of the 1H NMR spectra of enantiomers dissolved in chiral liquid
      crystals, combining variable angle sample spinning and selective refocusing
      experiments.
AB  - This work presents a technique to simplify overcrowded proton spectra in chiral
      liquid crystal solvents using rotation of the sample near the magic angle, VASS,
      combined with homonuclear selective refocusing 2D NMR experiments, SERF. This
      methodology provides a powerful tool to visualise enantiomers out of unresolved
      proton spectra. A modified SERF sequence is presented where the resulting 2D
      spectrum can be phased to increase the resolution. Accurate enantiomeric excesses
      are determined that are not possible to measure on static samples. Two examples
      are presented.

PMID- 16991109
TI  - A comparison of three different models for estimating relative risk in meta
      analysis of clinical trials under unobserved heterogeneity.
AB  - We focus on the comparison of three statistical models used to estimate the
      treatment effect in meta-analysis when individually pooled data are available.
      The models are two conventional models, namely a multi-level and a model based
      upon an approximate likelihood, and a newly developed model, the profile
      likelihood model which might be viewed as an extension of the Mantel-Haenszel
      approach. To exemplify these methods, we use results from a meta-analysis of 22
      trials to prevent respiratory tract infections. We show that by using the multi
      level approach, in the case of baseline heterogeneity, the number of clusters or
      components is considerably over-estimated. The approximate and profile likelihood
      method showed nearly the same pattern for the treatment effect distribution. To
      provide more evidence two simulation studies are accomplished. The profile
      likelihood can be considered as a clear alternative to the approximate likelihood
      model. In the case of strong baseline heterogeneity, the profile likelihood
      method shows superior behaviour when compared with the multi-level model.

PMID- 16991110
TI  - 15N NMR chemical shifts of ring substituted benzonitriles.
AB  - 15N chemical shifts in an extensive series of para (15) and meta (15) as well as
      ortho (8) substituted benzonitriles, X-C6H4-CN, were measured in
      deuteriochloroform solutions, using three different methods of referencing. The
      standard error of the average chemical shift was less than 0.03 ppm in most
      cases. The results are discussed for both empirical correlations with substituent
      parameters and quantum chemical calculations. The 15N chemical shifts calculated
      at the GIAO/B3LYP/6-31 + G*//B3LYP/6-31 + G* level reproduce the experimental
      values well, and include nitrogen atoms in the substituent groups (range of 300
      ppm with slope 0.98 and R = 0.998, n = 43). The 15N shifts in
      hydroxybenzonitriles are affected by interaction with the OH group. Therefore,
      these derivatives are excluded from the correlation analysis. The resultant 15N
      chemical shift correlates well with substituent constants, both in the simple
      Hammett or DSP relationships and the 13C substituent-induced chemical shifts of
      the CN carbon.

PMID- 16991111
TI  - The structure of ammonium pyrazolates in the solid state.
AB  - The crystals obtained by mixing equimolar amounts of diethyl 1H-pyrazole-3,5
      dicarboxylate and the primary amines phenethylamine and homoveratrylamine are
      ammonium pyrazolate salts as determined by 13C and 15N CPMAS NMR.

PMID- 16991112
TI  - The NMR studies on two new furostanol saponins from Agave sisalana leaves.
AB  - The detailed NMR studies and full assignments of the 1H and 13C spectral data for
      two new furostanol saponins isolated from Agave sisalana leaves are described.
      Their structures were established using a combination of 1D and 2D NMR techniques
      including 1H, 13C, 1H-1H COSY, TOCSY, HSQC, HMBC and HSQC-TOCSY, and also FAB-MS
      spectrometry and chemical methods. The structures were established as (25S)-26
      (beta-D-glucopyranosyl)-22 xi-hydroxyfurost-12-one-3beta-yl-O-alpha-L
      rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-O-[O-beta-D-glucopyranosyl
      (1-->2)]-O-beta-D-glucopyranosyl-(1-->4)-beta-D-galacto- pyranoside (1) and (25S)
      26-(beta-D-glucopyranosyl)-22xi-hydroxyfurost-5-en-12-one-3beta-yl-O-alpha-L
      rhamno- pyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-O-[O-beta-D
      glucopyranosyl-(1-->2)]-O-beta-D-glucopyranosyl- (1-->4)-beta-D-galactopyranoside
      (2).

PMID- 16991116
TI  - Localized short-echo-time proton MR spectroscopy with full signal-intensity
      acquisition.
AB  - We developed a short-echo-time (TE) sequence for proton localized spectroscopy by
      combining a 1D add-subtract scheme with a doubly slice-selective spin-echo (SE)
      sequence. The sequence preserves the full magnetization available from the
      selected volume of interest (VOI). By reducing the number of radiofrequency (RF)
      pulses acting on transverse magnetization, we were able to minimize the TE to the
      level that is achievable with the stimulated echo acquisition mode (STEAM)
      technique, and also gained a twofold increase in sensitivity. The use of an
      adiabatic pulse in the add-subtract localization improved the efficiency of
      excitation in spatially inhomogeneous RF fields, which are frequently encountered
      at high magnetic fields. The localization performance and sensitivity gains of
      this method, which is termed SPin ECho, full Intensity Acquired Localized
      (SPECIAL) spectroscopy, were demonstrated in vivo in rat brains. In conjunction
      with spectroscopic imaging, a 2-microl spatial resolution was accomplished with a
      signal-to-noise ratio (SNR) above 30, which is usually sufficient for reliable
      quantification of a large number of metabolites (neurochemical profile).

PMID- 16991114
TI  - Gene targeting of ErbB3 using a Cre-mediated unidirectional DNA inversion
      strategy.
AB  - Recombinase-mediated unidirectional DNA inversion and transcriptional arrest is a
      promising strategy for high throughput conditional mutagenesis in the mouse.
      Banks of mouse embryonic stem cells with defined, transcriptionally silent
      insertions that can be activated by Cre recombinase would take advantage of
      existing transgenic Cre lines to rapidly produce hundreds of lineage specific and
      temporally controlled knockout mice for each gene, thereby introducing
      significant parallelism to functional gene annotation. However, the extent to
      which this strategy results in effective gene knockout has not been established.
      To test the feasibility of this strategy we targeted ErbB3, a member of the ErbB
      family of tyrosine kinase receptors, using this strategy. Insertion of a reversed
      "flipflox" vector consisting of a gene inactivation cassette (GI) and an internal
      ribosome entry site (IRES)-GFP reporter into intron 1 of ErbB3 was
      transcriptionally silent and did not affect ErbB3 expression. Crosses with
      ubiquitous and lineage specific Cre recombinase expressing lines permanently
      inverted the inserted GI cassette and blocked ErbB3 expression. Unidirectional
      DNA inversion by in vivo recombination is an effective strategy for targeted or
      ubiquitous gene knockout.

PMID- 16991117
TI  - Diverse chromosome breakage mechanisms underlie subtelomeric rearrangements, a
      common cause of mental retardation.
AB  - Subtelomeric rearrangements are an important cause of both isolated and familial
      idiopathic mental retardation. A variety of different rearrangements such as pure
      truncations, unbalanced translocations, interstitial deletions, and inverted
      duplications have been detected throughout various screening studies. The cause
      of these aberrations is poorly understood as only few of the breakpoints have
      been determined and studied. We molecularly characterized the breakpoints of
      three rearrangements including a 1p subtelomeric deletion, a 1q subtelomeric
      deletion, and an unbalanced translocation between chromosomes 11q and 20q; we
      propose that diverse chromosome breakage mechanisms underlie subtelomeric
      rearrangements. The breakpoint sequences suggest that unusual non-B-DNA
      structures including triplex, tetraplex, and hairpin structures may be involved.
      In addition, we saw that the seemingly pure truncations of chromosomes 1p and 1q
      were in fact more complex rearrangements as highly repetitive sequences were
      joined to the chromosome end at the site of breakage.

PMID- 16991118
TI  - Generation of activin receptor type IIB isoform-specific hypomorphic alleles.
AB  - Activin receptor type IIB (Acvr2b) mediates multiple signals for transforming
      growth factor-beta (TGF-beta) family members, including Activin, Nodal, Bmp7,
      Gdf1, Gdf3, Myostatin (Gdf8), and Gdf11. Mouse Acvr2b gene generates four
      transcriptional isoforms (Acvr2b(1-4)) via alternative splicing of two sequence
      domains located at the juxtaposition of the transmembrane domain. To investigate
      whether these splicing domains are essential for signal transduction of the
      Acvr2b receptor in vivo, we have generated a strain of mutant mice (Acvr2b(4/4))
      which produce only the Acvr2b(4) isoform, which lacks both splicing domains. Most
      homozygous Acvr2b(4(neo)/4(neo)) mice, in which a neomycin-resistant cassette was
      inserted in Intron 4 displayed a mild form of anterior vertebral transformations.
      However, the penetrance of the vertebral defect was dramatically decreased when
      the neomycin-resistant cassette was deleted. These results suggest that the
      Acvr2b(4) isoform is capable of compensating for the deficiency of the other
      three isoforms. In the absence of its subfamily receptor Acvr2a, however, the
      development of Acvr2b(4/4) mice was arrested at the gastrulation stage,
      recapitulating the Acvr2a(-/-); Acvr2b(+/-) mutant phenotype. In this study, we
      demonstrate that this phenomenon is most likely due to the reduction in the
      expressed Acvr2b(4) levels rather than to the functional deficiency of the
      Acvr2b(4) isoform itself.

PMID- 16991119
TI  - Human papillomavirus as a risk factor for the increase in incidence of tonsillar
      cancer.
AB  - Smoking and alcohol are well-known etiological factors in tonsillar cancer.
      However, as in cervical cancer, human papillomavirus (HPV) is currently found in
      a sizable proportion of tonsillar cancer. Recent reports from the U.S. and
      Finland show an increase in the incidence of tonsillar cancer, without a parallel
      rise in smoking and alcohol consumption. This study investigates whether the
      incidence of tonsillar cancer has also changed in Sweden and whether a possible
      explanation of the increase is a higher proportion of HPV-positive tonsillar
      cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm
      area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment
      paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients
      in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence
      of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to
      2002. During the same period, a significant increase in the proportion of HPV
      positive tonsillar cancer cases was observed, as it increased 2.9-fold (p <
      0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s,
      12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000
      2002. We have demonstrated a highly significant and parallel increase both in the
      incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence,
      HPV may play an important role for the increased incidence of tonsillar cancer.
      This should definitely influence future preventive strategies as well as
      treatment for this type of cancer.

PMID- 16991120
TI  - Increased plasma DNA integrity index in head and neck cancer patients.
AB  - Analysis of the length of circulating DNA in plasma has been reported as a marker
      for solid tumor detection. We assessed the sensitivity and specificity of
      increased plasma DNA length to identify patients with head and neck squamous cell
      carcinoma (HNSCC) and monitor posttreatment disease status. Fifty-eight HNSCC
      patients with paired pre- and postoperative plasma and 47 plasma samples from
      control subjects were analyzed using quantitative PCR to determine plasma DNA
      integrity index. We found that the mean DNA integrity index was significantly
      greater in the plasma from HNSCC patients, 0.24 (95% CI: 0.11, 0.38), when
      compared to plasma from the control subjects, -2.24 (95% CI: -2.92, -1.56), p <
      0.0001 using multivariate analysis. The optimal sensitivity (the value for which
      sensitivity equals specificity) was found at a plasma DNA integrity index of
      0.82: sensitivity, 84.5%; specificity, 83%. However, there was no significant
      difference noted between pre- and postoperative DNA integrity index in plasma
      samples from HNSCC patients. This study shows that DNA integrity index in the
      plasma of the patients with HNSCC is increased in comparison with that in the
      plasma from non-HNSCC control subjects. Lack of normalization of plasma DNA
      integrity index after surgical resection implies the persistence of a population
      of cells with an altered pattern of DNA degradation despite removal of
      malignancy.

PMID- 16991121
TI  - Variations in the age-specific curves of human papillomavirus prevalence in women
      worldwide.
AB  - An inverse relationship between age and human papillomavirus (HPV) prevalence has
      been reported in many developed countries, but information on this relationship
      is scarce in many other parts of the world. We carried out a cross-sectional
      study of sexually active women from the general population of 15 areas in 4
      continents. Similar standardised protocols for women's enrolment, cervical
      specimen collection and PCR-based assays for HPV testing were used. HPV
      prevalence in different age groups was compared by study area. 18,498 women aged
      15-74 years were included. Age-standardised HPV prevalence varied more than 10
      fold between populations, as did the shape of age-specific curves. HPV prevalence
      peaked below age 25 or 35, and declined with age in Italy, the Netherlands,
      Spain, Argentina, Korea and in Lampang, Thailand and Ho Chi Minh, Vietnam. This
      was not the case in Songkla, Thailand nor Hanoi, Vietnam, where HPV prevalence
      was low in all age groups. In Chile, Colombia and Mexico, a second peak of HPV
      prevalence was detected among older women. In the poorest study areas in Asia
      (Shanxi, China and Dindigul, India), and in Nigeria, HPV prevalence was high
      across all age groups. The substantial differences observed in age-specific
      curves of HPV prevalence between populations may have a variety of explanations.
      These differences, however, underline that great caution should be used in
      inferring the natural history of HPV from age-specific prevalences.

PMID- 16991122
TI  - Urinary biomarker profiling in transitional cell carcinoma.
AB  - Urinary biomarkers or profiles that allow noninvasive detection of recurrent
      transitional cell carcinoma (TCC) of the bladder are urgently needed. We obtained
      duplicate proteomic (SELDI) profiles from 227 subjects (118 TCC, 77 healthy
      controls and 32 controls with benign urological conditions) and used linear mixed
      effects models to identify peaks that are differentially expressed between TCC
      and controls and within TCC subgroups. A Random Forest classifier was trained on
      130 profiles to develop an algorithm to predict the presence of TCC in a randomly
      selected initial test set (n = 54) and an independent validation set (n = 43)
      several months later. Twenty two peaks were differentially expressed between all
      TCC and controls (p < 10(-7)). However potential confounding effects of age, sex
      and analytical run were identified. In an age-matched sub-set, 23 peaks were
      differentially expressed between TCC and combined benign and healthy controls at
      the 0.005 significance level. Using the Random Forest classifier, TCC was
      predicted with 71.7% sensitivity and 62.5% specificity in the initial set and
      with 78.3% sensitivity and 65.0% specificity in the validation set after 6
      months, compared with controls. Several peaks of importance were also identified
      in the linear mixed effects model. We conclude that SELDI profiling of urine
      samples can identify patients with TCC with comparable sensitivities and
      specificities to current tumor marker tests. This is the first time that
      reproducibility has been demonstrated on an independent test set analyzed several
      months later. Identification of the relevant peaks may facilitate multiplex
      marker assay development for detection of recurrent disease.

PMID- 16991123
TI  - Heritable and environmental components in cervical tumors.
AB  - The familial risk of 18,199 women with invasive and/or in situ cervix cancers
      when compared with that of 72,796 women free of cervical tumors was analyzed. The
      risk of cervical tumors was significantly higher for women with a mother and/or
      sister(s) with cervical tumors (odds ratio (OR) = 1.79, 95% CI: 1.71-1.88) than
      with an affected grandmother and/or aunt(s) (OR = 1.28, 1.22-1.35). This risk did
      not differ according to the family side of the affected relative. Taking the
      familial risk of 1.28 for second-degree relatives as the best estimate of a true
      heritable effect for 25% of gene sharing, the calculated heritable effect for
      full siblings, sharing 50% of their genes, would correspond to an OR of 1.56.
      This model suggests, as a best estimate, a heritable component of 71% and an
      environmental component of 29% in young familial cervical tumors. The data imply
      that familial risks for cervical tumors are best explained by complex
      multifactorial mechanisms.

PMID- 16991124
TI  - Induction of protective immunity to RM-1 prostate cancer cells with ALVAC-IL-2/IL
      12/TNF-alpha combination therapy.
AB  - Human prostate cancers characteristically express low levels of major
      histocompatibility complex (MHC) Class I, which makes it challenging to induce
      protective antitumor responses involving T cells. Here we demonstrate that a
      whole cell tumor vaccine can induce protective T cell immunity to a low MHC Class
      I-expressing mouse prostate cancer cell line, RM-1. ALVAC recombinant canarypox
      viruses encoding interleukin-2, interleukin-12 and tumor necrosis factor-alpha
      were used to create therapeutic vaccines in 2 different ways. The RM-1 cells were
      pre-infected in vitro with the viruses prior to injection (pre-infection vaccine)
      or the RM-1 cells were injected alone, followed by the viruses (separate
      injection vaccine). The vaccines were each tested subcutaneously or
      intradermally. The pre-infection vaccine resulted in 100% clearance of primary
      tumors, whereas intradermal delivery of the separate injection vaccine cleared 40
      60% of primary tumors. Despite the highly efficient primary tumor clearance by
      the pre-infection vaccine, only the separate injection vaccine generated
      protection upon rechallenge. Tumor-free survival induced by the separate
      injection vaccine required natural killer (NK) cells, CD4(+), and CD8(+) T cells.
      None of these cells alone were sufficient to induce tumor-free survival to the
      primary challenge, demonstrating an important cooperativity between NK cells and
      T cells. Secondary clearance of tumors also required NK and CD8(+) T cells, but
      not CD4(+) T cells. We report for the first time the generation of T cell
      immunity to the RM-1 prostate cancer cell line, demonstrating that it is possible
      to generate protective T cell immunity to a MHC I-low expressing tumor.

PMID- 16991125
TI  - Wnt signaling promoter hypermethylation distinguishes lung primary
      adenocarcinomas from colorectal metastasis to the lung.
AB  - Promoter hypermethylation is responsible for gene inactivation during
      carcinogenesis. It has been proposed that there is some degree of specificity in
      the set of genes that become altered by this mechanism in distinct tumor types.
      To understand whether promoter hypermethylation may differentiate the site of
      origin, 49 lung adenocarcinomas from 31 lung primaries and 18 metastases from
      colorectal primaries, respectively, were tested for the presence of this
      alteration in the APC, CDH1, DAPK, GSTP1, MLH1, MGMT, P14, P16, RARbeta2, RASSF1,
      sFRP1 and WIF-1 genes. A distinct profile was apparent for the 2 groups of lung
      tumors and the frequencies of promoter hypermethylation at sFRP1 and WIF-1, 2
      genes involved in Wnt signaling, and at CDH1 were significantly higher in
      colorectal metastases than in lung primaries, whereas methylation of the APC
      promoter was significantly more common in lung primary adenocarcinomas. Some
      tumors showed concomitant APC, sFRP1 and WIF-1 gene inactivation, indicating that
      multiple DNA methylation events must have occurred to definitively down-regulate
      the signaling through Wnt. However, promoter hypermethylation at the APC and CDH1
      genes tended to be mutually exclusive (Fisher's exact test, p = 0.006),
      suggesting a similar role in carcinogenesis. In conclusion, we propose that
      inactivation by promoter hypermethylation at the APC, CDH1, sFRP1 and WIF-1 genes
      may contribute to the discrimination of lung primary adenocarcinomas from
      colorectal metastasis to the lung, and report the simultaneous presence of
      methylation at the promoters of multiple genes involved in the Wnt signaling.
      This may have biological consequences for carcinogenesis.

PMID- 16991126
TI  - Second primary oral and pharyngeal cancers in subjects diagnosed with oral and
      pharyngeal cancer.
AB  - Patients diagnosed with oral and pharyngeal (OP) cancer have a substantial excess
      risk of second OP cancer, but risk quantification is still uncertain and scanty
      information is available on the absolute excess risk of second OP cancer. We
      considered the risk of second OP primary cancer in a population-based series of
      3,092 first primary OP cancers registered between 1974 and 2003 in the Swiss
      Cantons of Vaud and Neuchatel (total population of about 786,000 inhabitants). A
      total of 233 second OP cancers were registered, versus 7.4 expected,
      corresponding to a SIR of 31.7 (95% confidence interval (CI) 27.7-36.0). The SIR
      was 68.5 in the first year after diagnosis of the first primary, and declined
      thereafter, leveling around 20. The SIR was 30.7 when the site of first neoplasm
      was the oral cavity, 42.5 for the tongue and 28.1 for the oropharynx or hypo
      pharynx. Corresponding values for topographies of second primaries were 28.8,
      50.4 and 26.2. The cumulative risk of second OP cancer 15 years after diagnosis
      of first OP cancer approached 22% in men and 17% in women. The incidence of first
      primaries increased over 20-fold between age 30-39 and 70-79, whereas there was
      no rise with age for second neoplasms.

PMID- 16991127
TI  - Mitochondrial microsatellite instability of colorectal cancer stroma.
AB  - Mitochondrial microsatellite instability (mtMSI) and mutations of mitochondrial
      DNA has been reported in cancer epithelia of carcinomas. However, mtMSI in cancer
      stroma has not yet been identified in human cancers. In this study, we attempted
      to determine if mtMSI occurs in the cancer stroma of sporadic colorectal cancers,
      and if the stromal mtMSI has any correlations with stromal nuclear MSI (nMSI) and
      cancer epithelial mtMSI. Nine microsatellite sequences within the D-loop and 5
      coding genes for mtMSI, and 9 microsatellites for nMSI were analyzed in the
      microdissected cancer epithelia and adjacent stromas of 48 sporadic colorectal
      cancers. Overall, 23 somatic mitochondrial DNA alterations were detected in 15
      cancer epithelia (31.2%) and 5 stromas (10.4%). The mutations consisted of 19 D
      loop mtMSI alterations, and 1 missense and 3 framshift mutations of repeat
      sequences within the coding genes. All of the 5 stromal genetic alterations
      showed D-loop mtMSI. In regards to other MSI status, the stromal mtMSI had no
      association with stromal nMSI or epithelial mtMSI, either. These findings
      indicate that in addition to the cancer epithelia the cancer stroma harbor mtMSI,
      and suggest a possible role of stromal mtMSI in the pathogenesis of colorectal
      cancers. Furthermore, the data suggest that stromal mtMSI may occur independently
      of stromal nMSI and epithelial mtMSI in sporadic colorectal cancers.

PMID- 16991128
TI  - Seroprevalence atlas of infections with oncogenic and non-oncogenic human
      papillomaviruses in Finland in the 1980s and 1990s.
AB  - Vaccines against high-risk (hr) human papillomaviruses (HPVs) causing cervical
      cancer may soon be licensed. Thus, nature of HPV epidemics needs to be studied
      now. Random sampling for studies on HPV epidemiology was done from all 230,998
      women belonging to the population-based Finnish Maternity Cohort and having a
      minimum of 2 pregnancies between 1983 and 1994. First pregnancy serum specimens
      were retrieved for 7,805 subjects, and were analyzed for antibodies to HPV6/11,
      16 and 18 with standard ELISAs. HPV16 seroprevalence almost doubled from the
      1980s to the 1990s, and the epidemic spread to new areas in 23-31 year olds, i.e.
      the bulk of pregnant female population in the southwest part of the country. The
      HPV16 epidemic in the 14-22 year olds in 1983-1988 (1961-1974 birth cohorts) and
      in the 23-31 year olds in 1989-1994 (1958-1971 birth cohorts) overlapped with
      strong clustering of HPV16 and HPV18 infections in the latter (odds ratio 8.0,
      95% confidence interval 6.6-9.7). Similar clustering of HPV16 and HPV6/11
      infections was not found. The epidemic and the clustering may be due to high
      transmission probability of the hrHPV types and increase in sexual activity of
      the index birth cohorts.

PMID- 16991129
TI  - Meat consumption and risk of colorectal cancer: a meta-analysis of prospective
      studies.
AB  - Accumulating epidemiologic evidence indicates that high consumption of red meat
      and of processed meat may increase the risk of colorectal cancer. We
      quantitatively assessed the association between red meat and processed meat
      consumption and the risk of colorectal cancer in a meta-analysis of prospective
      studies published through March 2006. Random-effects models were used to pool
      study results and to assess dose-response relationships. We identified 15
      prospective studies on red meat (involving 7,367 cases) and 14 prospective
      studies on processed meat consumption (7,903 cases). The summary relative risks
      (RRs) of colorectal cancer for the highest vs. the lowest intake categories were
      1.28 (95% confidence interval (CI) = 1.15-1.42) for red meat and 1.20 (95% CI =
      1.11-1.31) for processed meat. The estimated summary RRs were 1.28 (95% CI = 1.18
      1.39) for an increase of 120 g/day of red meat and 1.09 (95% CI = 1.05-1.13) for
      an increase of 30 g/day of processed meat. Consumption of red meat and processed
      meat was positively associated with risk of both colon and rectal cancer,
      although the association with red meat appeared to be stronger for rectal cancer.
      In 3 studies that reported results for subsites in the colon, high consumption of
      processed meat was associated with an increased risk of distal colon cancer but
      not of proximal colon cancer. The results of this meta-analysis of prospective
      studies support the hypothesis that high consumption of red meat and of processed
      meat is associated with an increased risk of colorectal cancer.

PMID- 16991130
TI  - Reversal of doxorubicin resistance in breast cancer cells by photochemical
      internalization.
AB  - Multiple drug resistance (MDR) is a problem that seriously reduces the efficacy
      of many chemotherapy agents. One mechanism for MDR is increased acidification of
      endocytic vesicles and increased cytosol pH, so weak base chemotherapeutic
      agents, including doxorubicin, are trapped in endocytic vesicles and exhibit a
      drug resistant phenotype. Treatments that selectively reverse this accumulation
      may therefore reverse the MDR phenotype. Photochemical internalization (PCI) is a
      novel technology developed for site-specific enhancement of the therapeutic
      efficacy of macromolecules by selective photochemical rupture of endocytic
      vesicles and consequent release of endocytosed macromolecules into the cytosol.
      This study evaluates PCI for release of doxorubicin from endocytic vesicles in
      MDR cells. Two breast cancer cell lines, MCF-7 and MCF-7/ADR (the latter
      resistant to doxorubicin), were selected. They were found equally sensitive to
      photochemical treatment with the photosensitiser TPPS(2) (a) (disulfonated meso
      tetraphenylporphine) and light. On exposure to doxorubicin alone, the IC(50)
      (drug concentration for 50% reduction in colony formation) was 0.1 microM for MCF
      7 and 1 microM for MCF-7/ADR. After PCI (photochemical treatment followed by
      doxorubicin), the IC(50) concentration was 0.1 microM for both cell lines.
      Comparable changes were seen with assay of cell viability using 3-(4,5
      dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). On fluorescence
      microscopy in MCF-7/ADR cells, doxorubicin localised in granules identified as
      lysosomes. After PCI, doxorubicin was released into the cytosol and entered cell
      nuclei, as was seen in MCF-7 cells without PCI. In conclusion, PCI reversed the
      MDR phenotype of doxorubicin resistant breast cancer cells by endo-lysosomal
      release of the drug. The technique is a promising new approach to tackling the
      problem of MDR.

PMID- 16991131
TI  - The PedsQL Brain Tumor Module: initial reliability and validity.
AB  - BACKGROUND: Brain tumors (BT) are second only to acute lymphoblastic leukemia as
      the most prevalent form of pediatric cancer, with BT 5-year survival rates
      approaching 70%. With increased survival, quality of life has emerged as an
      essential health outcome. This investigation examines the internal consistency
      reliability and construct validity of the Pediatric Quality of Life Inventory
      (PedsQL) Brain Tumor Module. METHODS: The PedsQL 4.0 Generic Core Scales, PedsQL
      Multidimensional Fatigue Scale, and PedsQL Brain Tumor Module were administered
      to 99 families. The average age of the 56 boys and 43 girls was 9.76 years
      (range=2-18 years). The sample included children with tumors located in the
      posterior fossa/brainstem (N=62, 62.6%), supratentorial (N=15, 15.2%), and
      midline (N=22, 22.2%). Children were on treatment (N=46, 46.5%), off treatment<12
      months (N=19, 19.2%), or off treatment>12 months/long-term survivor (N=34,
      34.3%). Treatment included radiation (N=61, 61.6%), surgery (N=83, 83.8%),
      chemotherapy (N=87, 87.9%), and bone marrow transplant (N=5, 5.1%). RESULTS:
      Internal consistency reliability was demonstrated for the 24-item PedsQL Brain
      Tumor Module (average alpha=0.78-0.92, parent proxy-report, n=99; average
      alpha=0.76-0.87, child self-report, n=51). Construct validity for the PedsQL
      Brain Tumor Module was supported through an analysis of the intercorrelations
      with the Generic Core Scales and Fatigue Scale. CONCLUSIONS: The findings provide
      support for the measurement properties of the PedsQL Brain Tumor Module.

PMID- 16991132
TI  - Evaluation of a pediatric palliative care educational workshop for oncology
      fellows.
AB  - BACKGROUND: Recent efforts have focused on improving pediatric palliative care to
      relieve physical and psychological suffering throughout the course of illness, as
      well as to improve care at the end-of-life (EOL). One area of attention has been
      medical training, as healthcare providers have often reported feeling ill
      equipped to manage EOL issues. As a pilot study, we developed and evaluated a
      daylong educational workshop on pediatric palliative care for oncology fellows.
      PROCEDURE: Fellows (N = 32) from 20 hospitals participated in one of two
      workshops covering palliative care topics, such as pain/symptom management,
      communication, ethics, and bereavement. Training, knowledge, behavior, and
      attitudes regarding pediatric palliative care were assessed before the workshop,
      and knowledge was re-assessed immediately afterwards. RESULTS: Fellows reported a
      general lack of training in EOL care, and only 41% rated their education as at
      least "somewhat" adequate. Colleagues and personal experience were more often
      sources on EOL care, rather than formal classes or textbooks. Although fellows
      reported open attitudes toward palliative care, such as involving adolescents in
      decision-making, only half felt comfortable in the presence of a dying person.
      Fewer than half felt comfortable providing EOL care, managing families'
      expectations, or knowledgeable enough to discuss hospice with patients/families.
      Following the workshop, knowledge of palliative care increased significantly from
      75 to 85% correct. CONCLUSIONS: Fellows reported open beliefs about palliative
      care, but acknowledged weaknesses in their training and level of competence. The
      workshop showed efficacy in improving knowledge, but additional research is
      needed to evaluate larger educational initiatives and their long-term impact on
      clinical services and family satisfaction.

PMID- 16991133
TI  - Non-hematopoietic stem cell transplantation treatment of juvenile myelomonocytic
      leukemia: a retrospective analysis and definition of response criteria.
AB  - BACKGROUND: Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative
      disease of infancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is
      currently the only curative treatment modality, while the role of anti-leukemic
      therapy prior to HSCT is uncertain. A comparative evaluation of the efficacy of
      different clinical protocols and great variety of anti-neoplastic drugs applied
      pre-HSCT is hampered by the lack of uniform criteria of response. Classification
      schemas applied in other forms of leukemia are of little value, because in JMML
      therapy may result in divergent responses in solid organs compared to peripheral
      blood (PB). PROCEDURE: We therefore defined separate response criteria for white
      blood count (WBC), platelet count, liver size, and spleen size. We then
      retrospectively evaluated the efficacy of 129 treatment courses other than HSCT
      administered to 63 children with JMML. Treatment consisted of intensive therapy
      according to AML-type chemotherapy, maintenance-type combination therapy, and
      single agent therapy. To account for the variability observed in the natural
      course of disease, we also evaluated 32 episodes of "no therapy." RESULTS: Best
      responses within 3 months of initiation of therapy were highly variable for the
      four response criteria. In contrast to platelet count and liver size, there was a
      significant correlation between WBC or spleen size and therapy. Response rates
      for WBC and spleen size were best for purine analogs, etoposide, and cytarabine
      as single agents or for maintenance-type combination therapy. CONCLUSION: To
      rigorously test future therapeutic strategies in this rare disease an
      international consensus on the definition of response criteria will be helpful.

PMID- 16991134
TI  - Acute transient encephalopathy following paclitaxel treatment in an adolescent
      with a recurrent suprasellar germinoma.
AB  - Paclitaxel is an antineoplastic agent that is used in the treatment of a variety
      of solid tumors. Dose-limiting side effects of myelosuppression and peripheral
      neuropathy are well known. Paclitaxel has minimal penetration of the blood-brain
      barrier and central nervous system side effects are rare. However, transient
      encephalopathy following paclitaxel infusion has been described in adults but not
      in children. We present the case of a 14-year-old female with a recurrent
      suprasellar germinoma who developed an acute encephalopathy 4-6 hr following
      paclitaxel infusion.

PMID- 16991135
TI  - Thromboembolism in children with sarcoma.
AB  - BACKGROUND: Thromboembolism (TE) is a common complication and cause of death in
      adults with cancer. Cancer has been identified as a major risk factor in children
      with TE. However, the information regarding the epidemiology of TE in children
      with cancer, especially in association with childhood solid tumors, is scant.
      OBJECTIVE: To define the prevalence and epidemiology of TE in children with
      sarcoma. PROCEDURE: Hospital records of children </=18 years of age with sarcoma
      diagnosed and treated at McMaster Children's Hospital during January 1990 to
      December 2005 were reviewed for demographic details, details of diagnosis and
      therapy for sarcoma, and details of diagnosis and management of TE. Statistical
      analysis was performed using Fisher's exact t-test. RESULTS: Ten of 70 (14.3%;
      95% CI; 7.1, 24.7) patients with sarcoma developed symptomatic TE. Patients with
      CVL-dysfunction (n = 9) were at significantly higher risk for symptomatic TE
      compared to those without CVL dysfunction (n = 61) (55.5 vs. 8.2%; P = 0.002, 95%
      CI; 14.2, 80.5). Patients with pulmonary disease (n = 23) had higher prevalence
      of TE compared to those without pulmonary disease (n = 47) (26 vs.8.5%; P = 0.07,
      95% CI; -2.06, 37.2). Older patients, patients with metastatic disease and those
      with Ewing sarcoma had higher prevalence of TE. CONCLUSIONS: TE is a significant
      complication in children with sarcoma. Over 50% of patients with CVL dysfunction
      had symptomatic TE; such patients may warrant careful evaluation for associated
      TE. Large prospective studies are needed to define the epidemiology and identify
      risk factors predisposing to TE in children with sarcoma.

PMID- 16991136
TI  - Acute myelogenous leukemia associated with Ollier disease.
AB  - Ollier disease is a rare disorder characterized by the presence of multiple
      enchondromas and a propensity to develop malignancies. We report the case of a 7
      year-old Caucasian male with Ollier disease who developed acute myelogenous
      leukemia (AML). This report describes a patient with Ollier disease and AML and
      may offer a clue into the genetic pathogenesis of these disorders.

PMID- 16991137
TI  - Polymorphous hemangioendothelioma in a child with acquired immunodeficiency
      syndrome (AIDS).
AB  - Polymorphous hemangioendotheliomas (PH) are rare and borderline malignant tumors
      that are among the wide range of vascular tumors. We report here a 13-year-old
      male presenting with a history of weight loss, opportunistic infections, and
      lymphadenopathy. He was determined to be HIV positive and to have acquired
      immunodeficiency syndrome (AIDS). A biopsy of a femoral node was diagnostic of
      PH. His systemic lymphadenopathy appeared to resolve with anti-retroviral
      therapy. This tumor should be considered within the differential diagnoses of
      pediatric and immunocompromised patients.

PMID- 16991138
TI  - Association of olfactory dysfunction with incidental Lewy bodies.
AB  - Olfactory dysfunction is found in early Parkinson's disease (PD) and in
      asymptomatic relatives of PD patients. Incidental Lewy bodies (ILB), the presence
      of Lewy bodies in the brains of deceased individuals without a history of PD or
      dementia during life, are thought to represent a presymptomatic stage of PD. If
      olfactory dysfunction were associated with the presence of ILB, this would
      suggest that olfactory deficits may precede clinical PD. The purpose of this
      study was to determine the association of olfactory dysfunction during late life
      with ILB in the substantia nigra or locus ceruleus. Olfaction was assessed during
      the 1991-1994 and 1994-1996 examinations of elderly Japanese-American men
      participating in the longitudinal Honolulu-Asia Aging Study. Among those who
      later died and underwent a standardized postmortem examination, brains were
      examined for Lewy bodies in the substantia nigra and the locus ceruleus with
      hematoxylin and eosin stain. Lewy bodies in the brains of individuals without
      clinical PD or dementia were classified as ILB. There were 164 autopsied men
      without clinical PD or dementia who had olfaction testing during one of the
      examinations. Seventeen had ILB. The age-adjusted percent of brains with ILB
      increased from 1.8% in the highest tertile of odor identification to 11.9% in the
      mid-tertile to 17.4% in the lowest tertile (P = 0.019 in test for trend). Age
      adjusted relative odds of ILB for the lowest versus the highest tertile was 11.0
      (P = 0.02). Olfactory dysfunction is associated with ILB. If incidental Lewy
      bodies represent presymptomatic stage of PD, olfactory testing may be a useful
      screening tool to identify those at high risk for developing PD.

PMID- 16991139
TI  - Clinical implications of the diagnosis "atypical squamous cells, cannot exclude
      high-grade squamous intraepithelial lesion" in pregnant women.
AB  - BACKGROUND: Atypical squamous cells, cannot exclude high-grade squamous
      intraepithelial lesion (ASC-H) has a high predictive value for high-grade
      intraepithelial lesion (HSIL) in the general population. However, the
      significance of ASC-H in pregnant women remains to be elucidated. The objective
      of this study was to investigate the clinical implications and pathologic
      significance of ASC-H in pregnant women, so that these patients will be managed
      appropriately. METHODS: All Papanicolaou tests that were diagnosed as ASC-H in
      pregnant women over 1.5 years (total, 60 women) were reviewed and correlated with
      histologic and/or cytologic follow-up. High-risk type of human papillomavirus
      (HPV) status was also correlated with follow-up findings. The following
      cytomorphologic parameters were evaluated for each woman and were compared
      between the squamous intraepithelial lesion (SIL) follow-up group and the benign
      follow-up group: inflammatory background, the number of atypical cells, cell
      arrangement pattern, nuclear irregularity/grooves, hyperchromasia, and cell
      shape. RESULTS: Among 30 women who had histologic follow-up, 3 women (10%) had
      HSIL, and 13 women (43%) had low-grade intraepithelial lesion (LSIL). Among 32
      women who had cytologic follow-up, 2 women (6%) had HSIL, 3 women (9%) had LSIL,
      1 woman (3%) had ASC-H, and 3 women (9%) had atypical squamous cells of
      undetermined significance (ASCUS). HPV was detected in 24 of 43 women (56%). The
      cytomorphologic features were similar in the SIL follow-up group and the benign
      follow-up group. No specific cytomorphologic features that predicted underlying
      SIL were identified. CONCLUSIONS: ASC-H in pregnant women had a lower predictive
      value for an underlying HSIL compared with the general population. A positive HPV
      test result was not a good indicator for an underlying SIL, but a negative result
      appeared to be useful for ruling out an underlying HSIL. Because of low positive
      predictive value for HSIL and the difficult colposcopic examination, a more
      conservative follow-up may be reasonable for pregnant women who have a diagnosis
      of ASC-H. HPV testing may be used as an adjunctive test.

PMID- 16991140
TI  - Assessing fear of falling: Can a short version of the Activities-specific Balance
      Confidence scale be useful?
AB  - We present the process of further validation of the 16-item Activities-specific
      Balance Confidence scale (ABC-16) and a short version (ABC-6) derived by us, to
      assess balance confidence and fear of falling (FOF). The ABC-16 was administrated
      to three groups who were anticipated to have a range of balance confidence: 70
      patients with higher level gait disorders (HLGDs), 68 healthy controls, and 19
      patients with Parkinson's disease (PD). Item reduction was based on identifying
      items with the lowest scores (high FOF) among the patients. Internal consistency
      and discriminative validity were assessed using Cronbach's alpha and logistic
      regression, respectively. The intraclass correlation (ICC) between the short and
      long versions was assessed using a mixed model approach, accounting for the
      difference between the scores of the two versions. Six items were found to
      reflect the most frightening conditions, especially in the patient groups, and to
      form the short version (ABC-6). Internal consistency of the ABC-16 and ABC-6 were
      high in the three groups: Cronbach's alpha was between 0.83 and 0.91 and 0.81 and
      0.90, respectively. Compared to the control group, the sensitivity of the ABC-16
      was 96% for identification of patients with HLGDs (greatest FOF) and 58% for
      identification of PDs (moderate FOF), based only on the ABC scores. Similar
      values were obtained for the short version, i.e., 91% for HLGDs and 53% for PDs.
      ICCs between the short and the long versions was 0.88 (HLGDs), 0.83 (PDs), and
      0.78 (Controls). To conclude, the short version of the ABC has properties
      analogous to the parent questionnaire and is apparently useful in assessing FOF.

PMID- 16991142
TI  - Adverse reaction after tetrathiomolybdate treatment for Wilson's disease: a case
      report.

PMID- 16991141
TI  - Parkinson's disease due to the R1441G mutation in Dardarin: a founder effect in
      the Basques.
AB  - The recent discovery of mutations in Dardarin (LRRK2) have been related to the
      appearance of Parkinson's disease in several families. Notably, one single
      mutation in this gene (R1441G) not only appeared in familial, but also in
      apparently sporadic Parkinson disease (PD) patients of Basque descent. A clinical
      population was ascertained, and subjects were classified into Basque and non
      Basque descent according to their known ancestry. The R1441G mutation was assayed
      using an allele-specific polymerase chain reaction, and several single nucleotide
      polymorphisms surrounding this mutation were analyzed by direct sequencing. In
      addition to 22 members of the original Basque families where R1441G was
      identified, we observed 17 carriers of the mutation who were apparently related
      through a common ancestor. From a clinical perspective, the disease observed in
      mutation carriers is indistinguishable from that in noncarriers. The R1441G
      mutation causes a form of Parkinson's disease that is equivalent to that observed
      in idiopathic Parkinson's disease. This mutation appears in 16.4% and 4.0% of
      familial and sporadic PD in this Basque population, respectively.

PMID- 16991143
TI  - Antiparkinsonian effects of the novel D3/D2 dopamine receptor agonist, S32504, in
      MPTP-lesioned marmosets: Mediation by D2, not D3, dopamine receptors.
AB  - L-dopa remains the most common treatment for Parkinson's disease. However, there
      is considerable interest in D3/D2 receptor agonists such as the novel agent
      S32504, since they exert antiparkinsonian properties in the absence of
      dyskinesia. An important question concerns the roles of D2 vs. D3 receptors, an
      issue we addressed with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      lesioned nonhuman primate model of Parkinson's disease. In L-dopa-primed animals,
      S32504 (0.16-2.5 mg/kg p.o.) dose-dependently enhanced locomotor activity. This
      action was abolished by the D2 antagonist, L741,626 (2.5 mg/kg), but potentiated
      by the D3 antagonist, S33084 (0.63 mg/kg). Both antagonists were inactive alone.
      In drug-naive animals, a maximally effective dose of S32504 (2.5 mg/kg p.o.)
      displayed pronounced antiparkinsonian properties from the third day of
      administration, and its actions were expressed rapidly and durably. Thus, on day
      33, antiparkinsonian properties of S32504 were apparent within 5 minutes and
      present for > 4 hours. Moreover, they were associated with neither wearing off
      nor significant dyskinesia. In conclusion, the novel D3/D2 agonist S32504 may
      offer advantages over L-dopa in the treatment of newly diagnosed parkinsonian
      patients. Its actions are expressed primarily by activation of D2, not D3,
      receptors.

PMID- 16991144
TI  - Patient selection and assessment recommendations for deep brain stimulation in
      Tourette syndrome.
AB  - In response to recent publicity regarding the potential use of deep brain
      stimulation (DBS) for reducing tic severity in Tourette's syndrome (TS), the
      Tourette Syndrome Association convened a group of TS and DBS experts to develop
      recommendations to guide the early use and potential clinical trials of DBS for
      TS and other tic disorders. The goals of these recommendations are to ensure that
      all surgical candidates are (1) fully informed about the risks, benefits, and
      alternative treatments available; (2) receive a comprehensive evaluation before
      surgery to ensure that DBS is clearly the appropriate clinical treatment choice;
      and (3) that early clinical experience will be documented publicly to facilitate
      rational decision-making for both clinical care and future clinical trials.

PMID- 16991145
TI  - Reversible Parkinsonism and T1W pallidal hyperintensities in acute liver failure.
AB  - We report on a young woman who survived acute liver failure (ALF) without liver
      transplant. During the ALF, she developed a disabling, levodopa-unresponsive,
      symmetrical Parkinsonism. This was characterized by severe bradykinesia, mild
      rigidity, mutism, and prominent gait impairment. Magnetic resonance imaging (MRI)
      showed bilateral T1W pallidal hyperintensities. Parkinsonism and MRI changes
      remitted in parallel with normalization of hepatic function. We implicate
      excessive pallidal manganese deposition secondary to ALF in the pathogenesis of
      this neuroradiological syndrome. Though hitherto unreported, we propose that
      Parkinsonism with T1W pallidal hyperintensities may not be uncommon in ALF.

PMID- 16991146
TI  - Direction of tremor oscillation in spiral drawings reveals proximal versus distal
      muscle involvement.

PMID- 16991147
TI  - Study of possible factors associated with age of onset in essential tremor.
AB  - Factors associated with the age of onset of essential tremor (ET) have not been
      studied in detail. Identification of modifiable factors could lead to strategies
      to delay disease onset and identification of nonmodifiable factors would be
      useful while counseling at risk individuals. The objective of this study was to
      identify factors associated with age of onset of tremor in ET. One hundred ninety
      five ET cases were enrolled in an environmental epidemiological study. Clinical
      questionnaires included questions on age of onset, demographics (age, sex, race,
      education), early-life exposures (birth order, childhood household size),
      exposures prior to tremor onset (head trauma, well water, rural living, estrogen
      replacement therapy), and family history. In unadjusted analyses, age of onset
      was associated with family history of tremor (40.9 +/- 22.0 years for cases with
      a family history of tremor vs. 57.3 +/- 18.4 years for cases without a history; P
      < 0.001), history of head trauma, younger current age, greater tremor severity,
      and white race. Ninety-one percent of cases with onset before age 20 years had a
      family history of tremor. Age ofonset was not associated with other variables of
      interest (e.g., sex, well water, rural living). In an adjusted linear regression
      model, age of tremor onset was strongly associated with family history of tremor
      (P < 0.001). The familial form of ET is characterized by an earlier age of onset
      than the sporadic form. This study did not detect any other exposures that
      modified the age of onset of ET. Follow-up studies are needed to examine
      additional factors of potential interest.

PMID- 16991148
TI  - Neuromotor deficits in children with the 22q11 deletion syndrome.
AB  - The 22q11 chromosomal deletion syndrome (22q11DS) is associated with a
      heterogeneous physical phenotype, neurocognitive deficits, and increased risk of
      later psychiatric illness. Sporadic clinical reports suggested motor differences,
      but quantitative studies of movement in children with 22q11DS are rare. If
      present in a majority of affected school-age children, characterization of
      neuromotor deficits may prove to be critical for intervention, neurocognitive
      test interpretation, and understanding etiology. We administered the Movement
      Assessment Battery for Children to 72 children ages 4.3 to 16.1, including 49
      children confirmed positive for the 22q11 deletion and 23 control siblings. We
      predicted a higher frequency of global and domain impairment in manual dexterity,
      eye-hand coordination, and balance among affected children. Ninety-four percent
      of affected children had marked neuromotor deficits, and group scores differed
      broadly for both global and subarea measures. Secondary analyses showed no
      impairment differences between younger and older children with 22q11DS, and
      longitudinal trajectories for 12 affected children suggested stability of
      deficits over 3-year intervals. Neuromotor deficits in children with 22q11DS
      occur early in development, continue throughout the school-age years, should be
      considered in the interpretation of motor-based achievement and IQ tests, and
      require targeted and ongoing remediation throughout childhood and adolescence.
      Further studies examining the specificity of motor impairment to 22q11DS are
      needed.

PMID- 16991149
TI  - Significance of intraoperative ureteral evaluation at radical cystectomy for
      urothelial cancer.
AB  - BACKGROUND: Patients undergoing radical cystectomy (RC) for urothelial cancer are
      at increased risk for upper tract recurrence and anastomotic recurrence. In an
      attempt to reduce this recurrence risk, urologists employ intraoperative frozen
      sections to achieve an uninvolved ureteral margin. The utility of this surgical
      approach was examined. METHODS: A retrospective review identified 1330 bladder
      cancer patients from 1990 to 2004 with pathologic evaluation of their ureters.
      Using pathologic findings on permanent section as the reference standard, the
      accuracy of ureteral frozen sections was examined. Ureteral involvement and
      margin status were examined as risk factors for upper tract and anastomotic
      recurrence and overall survival. RESULTS: Of 2579 ureteral margins evaluated in
      1330 patients, ureteral involvement was noted in 9% of ureters (13% of patients).
      The sensitivity and specificity of frozen section analyses were approximately 75%
      and 99%, respectively. The 5-year probability of anastomotic and upper tract
      recurrences was low: 2% and 13%, respectively. Evidence of involvement of the
      ureter or at the ureteral anastomotic margin was associated with higher
      likelihood of upper tract recurrence but not anastomotic recurrence or overall
      survival. Furthermore, sequential resection of ureters to reach a negative
      anastomotic ureteral margin did not eliminate the risk of anastomotic or upper
      tract recurrence. CONCLUSIONS: Patients with involved ureters and/or ureteral
      anastomotic margins have a higher risk of upper tract recurrence. However, the
      overall risk of recurrence is low and is not clearly associated with overall
      survival. The data do not support routine intraoperative frozen sections to
      assess ureteral involvement.

PMID- 16991150
TI  - Synchronized brain network underlying postural tremor in Wilson's disease.
AB  - Common neurological manifestation of Wilson's disease (WD) is a postural tremor
      of the upper extremities. Recently, the primary sensorimotor cortex (S1/M1) has
      been shown to be involved in WD postural tremor generation. However,
      neuropathological changes in WD are mostly observed in subcortical structures. We
      therefore aimed to investigate whether S1/M1 may be functionally interconnected
      with other brain areas. In five WD patients, we used magnetoencephalography and
      surface electromyography (EMG) to record simultaneously cerebral neuronal
      activity and muscular activity during sustained posture of the right forearm. As
      demonstrated previously, the strongest coupling to tremor EMG was observed in the
      contralateral S1/M1. This area was taken as reference in order to identify and
      localize cerebro-cerebral coherence at tremor frequency and its first harmonic.
      The analysis revealed significant coherence within an oscillatory network
      including S1/M1, higher cortical motor areas (premotor cortex, PM; supplementary
      motor area, SMA), posterior parietal cortex (PPC) and thalamus contralateral as
      well as the cerebellum ipsilateral to the tremor forearm. Flow of information was
      mainly of bidirectional nature. Taken together, our results indicate that WD
      postural tremor is generated within a synchronized cerebello-thalamo-cortical
      network, comprising S1/M1, higher cortical motor areas (SMA, PM), and PPC.

PMID- 16991155
TI  - Side and type of motor symptom influence cognition in Parkinson's disease.
AB  - It is well known that many patients with Parkinson's disease experience
      neuropsychological decline. However, the nature and extent of mental status
      change varies widely, with some patients showing mild or no cognitive impairments
      and others exhibiting frank dementia. Research has shown that several clinical
      disease parameters may differentially correlate with patterns of
      neuropsychological dysfunction. The present study examined side and type of motor
      symptom at disease onset and their relationship to cognition in idiopathic
      Parkinson's disease (PD). We identified 58 patients who initially presented with
      one of the following symptom profiles: right-side tremor onset (RSO-T; n = 15),
      right-side bradykinesia/rigidity onset (n = 12), left-side tremor onset (n = 19),
      and left-side bradykinesia/rigidity onset (n = 12). There were no differences
      between groups in disease duration, overall mental status, education, or
      depression severity. We administered a battery of neuropsychological measures to
      the four PD subgroups and a group of matched control subjects (n = 40). MANCOVAs
      controlling for age revealed patients with RSO-T performed significantly better
      than the other three PD subgroups across the entire neuropsychological battery.
      Further, the RSO-T subgroup performed comparably to controls. In contrast, the
      other three PD subgroups showed widespread cognitive deficits. These findings
      suggest an intricate relationship between motor symptom and side of disease onset
      and it is the combination of these factors that may influence the disease course
      and extent of cognitive deterioration. Furthermore, patients who develop tremor
      on the right side of their body represent a distinct subgroup of PD patients who
      exhibit relative sparing of cognitive function.

PMID- 16991156
TI  - Symptomatic restless leg syndrome after lacunar stroke: a lesion study.

PMID- 16991158
TI  - AgOC(CF3)3 and AgOSiiPr3-synthesis and characterization of a donor-free silver(I)
      alkoxide and silyl oxide.

PMID- 16991157
TI  - Cardiac [123I]metaiodobenzylguanidine scintigraphy for vascular Parkinsonism.
AB  - The purpose of our study was to prospectively evaluate cardiac
      [(123)I]metaiodobenzylguanidine (MIBG) uptake in patients with cerebrovascular
      disease (CVD) who develop clinical symptoms of vascular Parkinsonism (VP). A
      total of 19 consecutive patients who developed Parkinsonism during the course of
      their CVD were enrolled in the study; 16 age-matched subjects, and 30 patients
      with Parkinson's disease (PD) were also evaluated with cardiac MIBG uptake. MIBG
      uptake was assessed using the ratio of the heart to the upper mediastinum (H/M)
      according to planar scintigraphic data. The mean H/M ratio was significantly
      higher in patients with VP than in those with PD (2.28 +/- 0.41 vs. 1.27 +/-
      0.13; P < 0.001). MIBG uptake did not differ between VP and controls (2.46 +/-
      0.33; P > 0.05). Our findings suggest that myocardial postganglionic sympathetic
      dysfunction found in PD is absent in most patients with VP. MIBG single photon
      emission computed tomography imaging may be useful to help distinguish between PD
      and VP patients in clinical practice.

PMID- 16991159
TI  - Extending the scope of NMR spectroscopy with microcoil probes.
AB  - Capillary NMR (CapNMR) spectroscopy has emerged as a major breakthrough for
      increasing the mass-sensitivity of NMR spectroscopic analysis and enabling the
      combination of NMR spectroscopy with other analytical techniques. Not only is the
      acquisition of high-sensitivity spectra getting easier but the quality of CapNMR
      spectra obtained in many small-molecule applications exceeds what can be
      accomplished with conventional designs. This Minireview discusses current CapNMR
      technology and its applications for the characterization of mass-limited, small
      molecule and protein samples, the rapid screening of small-molecule or protein
      libraries, as well as hyphenated techniques that combine CapNMR with other
      analytical methods.

PMID- 16991160
TI  - Coordination-number dependence of reactivity in an imidoiron(III) complex.

PMID- 16991161
TI  - Strong neutral homoaromatics.

PMID- 16991162
TI  - Branch-selective intermolecular hydroacylation: hydrogen-mediated coupling of
      anhydrides to styrenes and activated olefins.

PMID- 16991164
TI  - The remarkable crossed co-isomerization reaction of cyclopropyl ketones and
      enones via nickeladihydropyrans.

PMID- 16991163
TI  - Two-directional annelation: dual benzyne cycloadditions starting from
      bis(sulfonyloxy)diiodobenzene.

PMID- 16991165
TI  - High-accuracy computation of reaction barriers in enzymes.

PMID- 16991166
TI  - New photoremovable protecting groups for carboxylic acids with high photolytic
      efficiencies at near-UV irradiation. Application to the photocontrolled release
      of L-glutamate.
AB  - We report here the syntheses and the photolytic properties of 3-(4,5-dimethoxy-2
      nitrophenyl)-2-butyl (DMNPB) esters as new photoremovable groups for carboxylic
      acids, and their use for the caging of L-glutamate. A high-yielding synthesis of
      the DMNPB esters led to a 4:1 threo/erythro diastereomeric mixture, which could
      be separated by HPLC. While these esters were stable in neutral buffer,
      photolysis at 364 nm induced a > or =95 % release of the carboxylic acid, with a
      0.26 quantum yield for L-glutamate formation. L-Glutamate release was also
      possible by two-photon photolysis with an action cross section of 0.17 GM at 720
      nm. Laser photolysis at 350 nm generated a transient species at around 410 nm,
      attributed to a quinonoid aci-nitro intermediate that decayed in the
      submillisecond time range (t(1/2)=0.53 ms) for the faster gamma-L-glutamyl threo
      esters. Given the absorbance of these esters (lambda(max)=350 nm; epsilon=4500),
      the threo DMNPB esters represent new caging groups that can be efficiently
      photolyzed at near-UV wavelengths. An efficient and rapid photolytic release of L
      glutamate has been demonstrated on hippocampal neurons in primary culture.

PMID- 16991167
TI  - Synthesis and evaluation of an intercalator-polyamide hairpin designed to target
      the inverted CCAAT box 2 in the topoisomerase IIalpha promoter.
AB  - The synthesis and DNA-binding properties of a novel naphthalimide-polyamide
      hairpin (3) designed to target the inverted CCAAT box 2 (ICB2) site on the
      topoisomerase IIalpha (topoIIalpha) promoter are described. The polyamide
      component of 3 was derived from the minor-groove binder, 2, and tailored to bind
      to the 5'-TTGGT sequence found in and flanking ICB2. The propensity of mitonafide
      4 to intercalate between G-C base pairs was exploited by the incorporation of a
      naphthalimide moiety at the N terminus of 2. Hybrid 3 targeted 5'-CGATTGGT and
      covered eight contiguous base pairs, which included the underlined ICB2 site.
      DNase I footprinting analysis with the topoIIalpha promoter sequence demonstrated
      that 3 bound selectively to the ICB2 and ICB3 sites. Thermal-denaturation studies
      confirmed these results, and the highest degree of stabilization was found for
      ICB2 and -3 in preference to ICB1 (4.1, 4.6, and 0.6 degrees C, respectively). CD
      studies confirmed minor-groove binding and suggested a 1:1 binding stoichiometry.
      Emission-titration experiments established intercalative binding. Surface plasmon
      resonance results showed strong binding to ICB2 (2.5x10(7) M(-1)) with no
      observable binding to ICB1. Furthermore, the binding constant of 3 to ICB2 was
      larger than that of the parent polyamide 2. The increased binding affinity was
      primarily due to a reduction in the dissociation-rate constant of the polyamide
      DNA complex, which can be attributed to the N-terminal naphthalimide moiety. In
      addition, the binding site of 3 was larger than that of 2, which innately
      improved sequence selectivity. We conclude that the polyamide-naphthalimide 3
      selectively binds to the ICB2 site by simultaneous intercalation and minor-groove
      binding, and warrants further investigation as a model compound for the
      regulation of topoIIalpha gene expression.

PMID- 16991168
TI  - Hierarchical mechanochemical switches in angiostatin.
AB  - We wish to propose a novel mechanism by which the triggering of a biochemical
      signal can be controlled by the hierarchical coupling between a protein redox
      equilibrium and an external mechanical force. We have characterized this
      mechanochemical mechanism in angiostatin, and we have evidence that it can switch
      the access to partially unfolded structures of this protein. We have identified a
      metastable intermediate that is specifically accessible under thioredoxin-rich
      reducing conditions, like those met by angiostatin on the surface of a tumor
      cell. The structure of the same intermediate accounts for the unexplained
      antiangiogenic activity of angiostatin. These findings demonstrate a new link
      between redox biology and mechanically regulated processes.

PMID- 16991169
TI  - Stereoselectivity, sequence specificity and mechanism of action of the azinomycin
      epoxide.

PMID- 16991170
TI  - Molecular basis for the enhanced lipase-catalyzed N-acylation of 1
      phenylethanamine with methoxyacetate.
AB  - One of the commercial methods for preparing enantiopure amines is lipase
      catalyzed kinetic resolution, although lipases catalyze aminolysis with only low
      activity. Interestingly, in 1997 Balkenhohl et al. used ethyl methoxyacetate
      instead of ethyl butyrate as an acylation reagent for the aminolysis of 1
      phenylethanamine and increased the reaction rate more than a 100-fold. This
      method has been applied to other aminolysis reactions, but the molecular basis
      for the enhanced rate is not understood. A molecular-modeling study of the
      transition-state analogue for the aminolysis showed that an interaction between
      the beta-oxygen atom in methoxyacetate and the amine nitrogen atom might be a key
      factor in the rate enhancement. Other acylation reagents, such as methyl 3
      methoxypropionate and methyl 4-methoxybutyrate, were chosen to test the influence
      of this interaction because these molecules can be spatially arranged to have
      similar interactions. The results were similar to that in the acylation with
      methoxyacetate. The initial aminolysis rates were improved (11-fold and sixfold,
      respectively) compared to that with butyrate. In contrast, alcoholysis with 1
      phenylethanol afforded the same rate with all acyl donors.

PMID- 16991171
TI  - Gas-phase protonation and deprotonation of acrylonitrile derivatives N[triple
      chemical bond]C--CH==CH--X (X=CH(3), NH(2), PH(2), SiH(3)).
AB  - A combined experimental and theoretical study on the gas-phase basicity and
      acidity of a series of cyanovinyl derivatives is presented. The gas-phase
      basicities and acidities of (N[triple chemical bond]C--CH==CH--X, X=CH(3), NH(2))
      were obtained by means of Fourier transform ion cyclotron resonance (FT-ICR) mass
      spectrometry techniques. The corresponding calculated values were obtained at the
      G3B3 level of theory. The effects of exchanging CH(3) for SiH(3), and NH(2) for
      PH(2), were analyzed at the same level of theory. For the neutral molecules, the
      Z isomer is always the dominant species under standard gas-phase conditions at
      298 K. The loss of the proton from the substituent X was found systematically to
      be much more favorable than deprotonation of the HC==CH linking group. The
      corresponding isomeric E ion is much more stable than the Z ion, so that only the
      former should be found in the gas phase. The most significant structural changes
      upon deprotonation occur for the methyl and amino derivatives because, in both
      cases, deprotonation of X leads to a significant charge delocalization in the
      corresponding anion. Protonation takes place systematically at the cyano group,
      whereby the isomeric E ion is again more stable than the Z ion. Push-pull effects
      explain the preference of aminoacrylonitrile to be protonated at the cyano group,
      which also explains the high basicity of this derivative relative to other
      members of the analyzed series that present rather similar gas-phase basicities,
      GB approximately 780 kJ mol(-1), indicating that the different nature of the
      substituents has only a weak effect on the intrinsic basicity of the cyano group.
      The cyanovinyl derivatives have a significantly stronger gas-phase acidity than
      that of the corresponding vinyl compounds CH(2)==CH--X. This acidity
      strengthening effect of the cyano group is attributed to the greater
      stabilization of the anion with respect to the corresponding neutral compound.

PMID- 16991172
TI  - Three-phase interlines electrochemically driven into insulator compounds: a
      penetration model and its verification by electroreduction of solid AgCl.
AB  - A dynamic three-phase interline model has been developed for the reduction of a
      solid insulating metal compound to the metal in a suitable electrolyte, focusing
      on the electrochemically driven penetration of the process (or the three-phase
      interlines) into the insulator. Consideration is given to the effects of
      electrochemical, concentration and ohmic polarizations in the reduction-generated
      porous metal layer on top of the solid compound. Under potentiostatic conditions,
      reduction in the depth direction (penetration) becomes progressively slower as a
      result of the rising ohmic and concentration polarizations, whilst the
      electrochemical polarization exerts a declining effect. The quantitative
      equations established here also provide simple methods for the determination of
      some kinetic parameters of the reduction process, including rho (total
      resistivity) and D(R) (diffusion coefficient). The model has been experimentally
      verified by electrochemical reduction of solid AgCl with two novel metal|AgCl
      cylinder electrodes in aqueous solutions.

PMID- 16991173
TI  - Aromatic ketones as photocatalysts: combined action as triplet photosensitiser
      and ground state electron acceptor.

PMID- 16991174
TI  - In silico ADMET traffic lights as a tool for the prioritization of HTS hits.
AB  - The need for in silico characterization of HTS hit structures as part of a data
      driven hit-selection process is demonstrated. A solution is described in the form
      of an in silico ADMET traffic light and PhysChem scoring system. This has been
      extensively validated with in-house data at Bayer, published data, and a
      collection of launched small-molecule oral drugs.

PMID- 16991175
TI  - Rational design of RGD-albumin conjugates for targeted delivery of the VEGF-R
      kinase inhibitor PTK787 to angiogenic endothelium.

PMID- 16991176
TI  - The hammerhead ribozyme structure brought in line.

PMID- 16991177
TI  - Endosialidase NF appears to bind polySia DP5 in a helical conformation.

PMID- 16991178
TI  - Shape-controlled synthesis of zinc oxide: a simple method for the preparation of
      metal oxide nanocrystals in non-aqueous medium.
AB  - A general and facile approach has been developed to prepare various metal oxide
      nanocrystals from commercially available metal acetate precursors using an amine
      mediated reaction. The influence of temperature and capping agents on the yield
      and final morphology of the metal oxides nanocrystals was investigated. The
      approach was applied in the synthesis of shape-controlled ZnO nanocrystals. ZnO
      nanowires, nanorods, bullets and triangular nanocrystals were successfully
      prepared by tuning the molar ratio between amine to zinc acetate precursor. On
      the basis of FTIR and NMR spectroscopic studies, we propose that the amine could
      mediate the breakdown of the metal acetates through a nucleophilic attack
      mechanism. The results suggest that amine can play dual role as both the
      attacking agent and capping agent in this new methodology.

PMID- 16991179
TI  - Ca2+- and ba2+-ligand coordinated unilamellar, multilamellar, and oligovesicular
      vesicles.
AB  - Ca(2+)- and Ba(2+)-coordinated vesicle phases were prepared in mixed aqueous
      solutions of tetradecyldimethylamine oxide (C(14)DMAO) and calcium oleate
      (Ca(OA)(2)) or barium oleate (Ba(OA)(2)). At the right mixing ratios, metal
      ligand coordination between Ca(OA)(2) or Ba(OA)(2) and C(14)DMAO results in the
      formation of molecular bilayers due to the reduction in area per head group.
      Ca(2+) and Ba(2+) tightly associate to the head groups of surfactants and in this
      system the bilayer membranes are not shielded by excess salts. The structures of
      the birefringent samples of the Ca(OA)(2)/C(14)DMAO/H(2)O and
      Ba(OA)(2)/C(14)DMAO/H(2)O systems were determined by freeze-fracture transmission
      electron microscopy (FF-TEM), small-angle X-ray scattering (SAXS), and
      rheological measurements to consist of unilamellar, multilamellar, and
      oligovesicular vesicles. The coordination between C(14)DMAO and Ba(OA)(2) or
      Ca(OA)(2) plays an important role in the formation of the vesicles, which was
      easily confirmed by studying the phase behavior of the KOA/C(14)DMAO/H(2)O system
      in which only the L(1) phase forms, due to the absence of coordination between
      KOA and C(14)DMAO. A mechanism is proposed that accounts for the formation of
      these new metal-ligand coordinated vesicles.

PMID- 16991180
TI  - Structure of the alpha-homo-DNA:RNA duplex and the function of twist and slide to
      catalogue nucleic acid duplexes.
AB  - High-resolution NMR studies of an alpha-homo-DNA:RNA duplex reveal the formation
      of a right-handed parallel-oriented helix. It differs significantly from a
      standard A- or B-type helix by a small twist value (26.2 degrees ), which leads
      to a helical pitch of 13.7 base pairs per helical turn, a negative inclination (
      1.78 Angstrom) and a large x displacement (5.90 Angstrom). The rise (3.4
      Angstrom) is similar to that found in B-DNA. The solution of this new helix
      structure has stimulated us to develop a mathematical and geometrical model based
      on slide and twist parameters to describe nucleic acid duplexes. All existing
      duplexes can be positioned within this landscape, which can be used to understand
      the helicalization process.

PMID- 16991181
TI  - meso-meso-Linked corrole dimers with modified cores: synthesis, characterization,
      and properties.
AB  - The synthesis and characterization of the first examples of core-modified corrole
      dimers linked through the meso positions are described. The dimers are obtained
      by a simple Ag(I)- or Fe(III)-catalyzed coupling reaction in near-quantitative
      yields. The corroles obtained are metalated with metal ions, such as Cu(II) and
      Ni(II). The electronic-absorption spectral studies reveal weak electronic
      interaction between the two subunits and the exciton coupling observed for the
      free-base corrole dimer (1717 cm(-1)) is lower than that for the corresponding
      protonated derivative (4081 cm(-1)). The solution-state structure derived from
      (1)H and two-dimensional NMR spectral studies reveals a noncoplanar arrangement
      of two corrole units. Geometry optimization at the B3LYP-631G level also confirms
      the noncoplanar arrangement of corroles with a dihedral angle of 64.8 degrees
      between two corrole planes. The electron paramagnetic resonance (EPR) and
      magnetic characterization studies on the paramagnetic copper-metalated dimer
      indicate that both copper ions behave as independent spins without any noticeable
      interaction. Results of fluorescence studies reveal a bathochromic shift of about
      60 nm upon dimerization. The first hyperpolarizability (beta) measured by using
      the hyper Rayleigh scattering (HRS) method reveals doubling of the beta values on
      progressing from monomer to dimer, attributed to enhanced pi conjugation. The use
      of copper dimers in the photocleavage of DNA is also explored. It is shown that
      the bimetallic copper dimer selectively cleaves the nucleic acids without
      affecting the proteins, suggesting a possible application of the copper complex
      in the removal of nucleic acid contaminants from protein extracts through a
      simple photolytic pathway.

PMID- 16991182
TI  - Iridium(III) silyl alkyl and iridacyclic compounds supported by 4,4'-di-tert
      butyl-2,2'-bipyridyl.
AB  - Treatment of IrCl(3)x H(2)O with one equivalent of 4,4'-di-tert-butyl-2,2'
      bipyridyl (dtbpy) in N,N-dimethylformamide (dmf) afforded [IrCl(3)(dmf)(dtbpy)]
      (1). Alkylation of 1 with Me(3)SiCH(2)MgCl resulted in C--Si cleavage of the
      Me(3)SiCH(2) group and formation of the Ir(III) silyl dialkyl compound
      [Ir(CH(2)SiMe(3))(dtbpy)(Me)(SiMe(3))] (2), which reacted with tBuNC to afford
      [Ir(tBuNC)(CH(2)SiMe(3))(dtbpy)(Me)(SiMe(3))] ([2(tBuNC)]). Reaction of 2 with
      phenylacetylene afforded dimeric [{Ir(C[triple chemical
      bond]CPh)(dtbpy)(SiMe(3))}(2)(mu-C[triple chemical bond]CPh)(2)] (3), in which
      the bridging PhC[triple chemical bond]C(-) ligands are bound to Ir in a mu
      sigma:pi fashion. Alkylation of 1 with PhMe(2)CCH(2)MgCl afforded the
      cyclometalated compound [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4))(2-C(6)H(4)CMe(3))] (4),
      which features an agostic interaction between the Ir center and the 2-tert
      butylphenyl ligand. The cyclic voltammogram of 4 in CH(2)Cl(2) shows a reversible
      Ir(IV)-Ir(III) couple at about 0.02 V versus ferrocenium/ferrocene. Oxidation of
      4 in CH(2)Cl(2) with silver triflate afforded an Ir(IV) species that exhibits an
      anisotropic electron paramagnetic resonance (EPR) signal in CH(2)Cl(2) glass at 4
      K with g( parallel)=2.430 and g( perpendicular)=2.110. Protonation of 4 with HCl
      and p-toluenesulfonic acid (HOTs) afforded [{Ir(dtbpy)(CH(2)CMe(2)Ph)Cl}(2)(mu
      Cl)(2)] (5) and [Ir(dtbpy)(CH(2)CMe(2)Ph)(OTs)(2)] (6), respectively. Reaction of
      5 with Li[BEt(3)H] gave the cyclometalated complex
      [{Ir(dtbpy)(CH(2)CMe(2)C(6)H(4))}(2)(mu-Cl)(2)] (7). Reaction of 4 with
      tetracyanoethylene in refluxing toluene resulted in electrophilic substitution of
      the iridacycle by C(2)(CN)(3) with formation of [Ir(dtbpy)(CH(2)CMe(2)C(6)H(3){4
      C(2)(CN)(3)})(2-C(6)H(4)CMe(3))] (8). Reaction of 4 with diethyl maleate in
      refluxing toluene gave the iridafuran compound
      [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4)){kappa(2)(C,O)-C(CO(2)Et)CH(CO(2)Et)}] (9).
      Treatment of 9 with 2,6-dimethylphenyl isocyanide (xylNC) led to cleavage of the
      iridafuran ring and formation of
      [Ir(dtbpy)(CH(2)CMe(2)C(6)H(4)){C(CO(2)Et)CH(CO(2)Et)}(xylNC)] (10). Protonation
      of 9 with HBF(4) afforded the dinuclear neophyl complex
      [(Ir(dtbpy)(CH(2)CMe(2)Ph){kappa(2)(C,O)-C(CO(2)Et)CH(CO(2)Et)})(2)][BF(4)](2)
      (11). The solid-state structures of complexes 2-5 and 8-11 have been determined.

PMID- 16991183
TI  - Mechanism of the copper-free palladium-catalyzed Sonagashira reactions: multiple
      role of amines.
AB  - Amines used as bases in copper-free, palladium-catalyzed Sonogashira reactions
      play a multiple role. The oxidative addition of iodobenzene with
      [Pd(0)(PPh(3))(4)] is faster when performed in the presence of amines
      (piperidine>morpholine). Amines also substitute one ligand L in trans
      [PdI(Ph)(L)(2)] (L=PPh(3), AsPh(3)) formed in the oxidative addition. This
      reversible reaction, which gives [PdI(Ph)L(R(2)NH)], is favored in the order
      AsPh(3)>PPh(3) and piperidine>morpholine. Two mechanisms are proposed for
      Sonogashira reactions, depending on the ligand and the amine. When L=PPh(3), its
      substitution by the amine in trans-[PdI(Ph)(PPh(3))(2)] is less favored than that
      of the alkyne. A mechanism involving prior coordination of the alkyne is
      suggested, followed by deprotonation of the ligated alkyne by the amine. When
      L=AsPh(3), its substitution in trans-[PdI(Ph)(AsPh(3))(2)] by the piperidine is
      easier than that by the alkyne, leading to a different mechanism: substitution of
      AsPh(3) by the amine is followed by substitution of the second AsPh(3) by the
      alkyne to generate [PdI(Ph)(amine)(alkyne)]. Deprotonation of the ligated alkyne
      by an external amine leads to the coupling product. This explains why the
      catalytic reactions are less efficient with AsPh(3) than with PPh(3) as ligand.

PMID- 16991184
TI  - Microreactors as tools for synthetic chemists-the chemists' round-bottomed flask
      of the 21st century?
AB  - Will microreactors replace the round-bottomed flask to perform chemical reactions
      in the near future? Recent developments in the construction of microstructured
      reaction devices and their wide-ranging applications in many different areas of
      chemistry suggest that they can have a significant impact on the way chemists
      conduct their experiments. Miniaturizing reactions offers many advantages for the
      synthetic organic chemist: high-throughput scanning of reaction conditions,
      precise control of reaction variables, the use of small quantities of reagents,
      increased safety parameters, and ready scale-up of synthetic procedures. A wide
      range of single- and multiphase reactions have now been performed in microfluidic
      based devices. Certainly, microreactors cannot be applied to all chemistries yet
      and microfluidic systems also have disadvantages. Limited reaction-time range,
      high sensitivity to precipitating products, and new physical, chemical, and
      analytical challenges have to be overcome. This concept article presents an
      overview of microfluidic devices available for chemical synthesis and evaluates
      the potential of microreactor technology in organic synthesis.

PMID- 16991185
TI  - Mossbauer investigation of the photoexcited spin states and crystal structure
      analysis of the spin-crossover dinuclear complex [{Fe(bt)(NCS)(2)}(2)bpym]
      (bt=2,2'-bithiazoline, bpym=2,2'-bipyrimidine).
AB  - The crystal structure of the complex [{Fe(bt)(NCS)(2)}(2)bpym] (1) (bt=2,2'
      bithiazoline, bpym=2,2'-bipyrimidine) has been solved at 293, 240, 175 and 30 K.
      At all four temperatures the crystal remains in the P space group with
      a=8.7601(17), b=9.450(2), c=12.089(3) A, alpha=72.77(2), beta=79.150(19),
      gamma=66.392(18) degrees , V=873.1(4) Angstrom(3) (data for 293 K structure). The
      structure consists of centrosymmetric dinuclear units in which each iron(II) atom
      is coordinated by two NCS(-) ions in the cis position and two nitrogen atoms of
      the bridging bpym ligand, with the remaining positions occupied by the peripheral
      bt ligand. The iron atom is in a severely distorted octahedral FeN(6)
      environment. The average Fe--N bond length of 2.15(9) Angstrom indicates that
      compound 1 is in the high-spin state (HS-HS) at 293 K. Crystal structure
      determinations at 240, 175 and 30 K gave a cell comparable to that seen at 293 K,
      but reduced in volume. At 30 K, the average Fe--N distance is 1.958(4) Angstrom,
      showing that the structure is clearly low spin (LS-LS). At 175 K the average Fe-
      N bond length of 2.052(11) Angstrom suggests that there is an intermediate phase.
      Mossbauer investigations of the light-induced excited spin state trapping
      (LIESST) effect (lambda=514 nm, 25 mW cm(-2)) in 1 (4.2 K, H(ext)=50 kOe) show
      that the excited spin states correspond to the HS-HS and HS-LS pairs. The
      dynamics of the relaxation of the photoexcited states studied at 4.2 K and
      H(ext)=50 kOe demonstrate that HS-HS pairs revert with time to both HS-LS and LS
      LS configurations. The HS-LS photoexcited pairs relax with time back to the
      ground LS-LS configuration. Complex [{Fe(0.15)Zn(0.85)(bt)(NCS)(2)}(2)bpym] (2)
      exhibits a continuous spin transition centred around 158 K in contrast to the two
      step transition observed for 1. The different spin-crossover behaviour observed
      for 2 is due to the decrease of cooperativity (intermolecular interactions)
      imposed by the matrix of Zn(II) ions. This clearly demonstrates the role of the
      intermolecular interactions in the stabilization of the HS-LS intermediate state
      in 1.

PMID- 16991187
TI  - Highly regioselective rhodium-catalysed hydroformylation of unsaturated esters:
      the first practical method for quaternary selective carbonylation.
AB  - Highly regioselective hydroformylation of unsaturated esters can be achieved when
      a highly reactive, ligand-modified, rhodium catalyst is employed near ambient
      temperatures (15-50 degrees C) and pressures over 30 bar. The use of 1,3,5,7
      tetramethyl-2,4,8-trioxa-6-phosphaadamantane shows distinct advantages over other
      commonly applied phosphanes in terms of reaction rate, and regio- and
      chemoselectivity. Hydroformylation of a range 1,1-di- and 1,1,2-trisubstituted
      unsaturated esters yields quaternary aldehydes that are forbidden products
      according to Keulemans Rule. The aldehydes can be reductively aminated with
      molecular hydrogen to give beta-amino acid esters in high yield. The overall
      green chemical process involves converting terminal alkynes into unusual beta
      amino acid esters with only water generated as an essential byproduct. This
      catalytic system has also been applied to the hydroformylation of simple 1,2
      disubstitued unsaturated esters, which have been hydroformylated with excellent
      alpha-selectivity and good chemoselectivity for the first time.

PMID- 16991186
TI  - Chiral oxazolopiperidone lactams: versatile intermediates for the
      enantioselective synthesis of piperidine-containing natural products.
AB  - Phenylglycinol-derived oxazolopiperidone lactams are exceptionally versatile
      building blocks for the enantioselective construction of structurally diverse
      piperidine-containing natural products and bioactive compounds. These lactams are
      readily available in both enantiomeric series by cyclocondensation of the chiral
      amino alcohol with a delta-oxo acid derivative and allow the substituents to be
      introduced at the different ring positions in a regio- and stereocontrolled
      manner, providing access to enantiopure polysubstituted piperidines bearing
      virtually any type of substitution pattern, and also quinolizidines,
      indolizidines, perhydroquinolines, hydroisoquinolines, as well as complex indole
      alkaloids. Of particular interest are cyclocondensation reactions with racemic or
      prochiral delta-oxo (di)acid derivatives in processes involving dynamic kinetic
      resolution and/or differentiation of enantiotopic or diastereotopic ester groups,
      as they directly lead to lactams that already incorporate the carbon substituents
      on the heterocyclic ring. The use of (S)-3,4-dimethoxyphenylalaninol or (S)
      tryptophanol in the above cyclocondensation reactions expands the potential and
      the scope of the methodology, providing a straightforward route to enantiopure
      benzo[a]- and indolo[2,3-a]quinolizidines.

PMID- 16991188
TI  - An efficient access to novel enantiomerically pure steroidal delta-amino acids.
AB  - A highly chemoselective sequence of Stille and Heck couplings on the heterocyclic
      bromoenol triflates 2 a-c with the bicycloalkenylstannanes cis-3 and trans-3
      furnished the intermediate bromobutadienes 4 a-c in good yields ranging from 73
      94 %. A modified Heck coupling protocol employing the palladacycle 8 and an
      additional bidentate ligand such as 1,4-bis(diphenylphosphinyl)butane allowed a
      significant reduction in catalyst loading while still obtaining the heterocyclic
      1,3,5-hexatrienes 5 a-c in good yields (71-94 %). The unsymmetrically substituted
      1,3,5-hexatrienes 5 a-c in solution underwent 6pi-electrocyclizations following
      an optimized microwave-heating protocol to yield the steroidal tetracycles cis-7
      a-c and trans-7 b (59-69 %). Tetracycles cis-7 a-c are the products of a
      subsequent 1,5-hydrogen shift to the thermodynamically more stable, more highly
      substituted diene units. Removal of the tert-butyl groups provided the novel
      steroidal delta-amino acid 9 a and the delta-amino acid derivatives 9 b, c in
      good yields (76-86 %).

PMID- 16991189
TI  - N-fusion reaction sequence of heptaphyrin(1.1.1.1.1.1.1): singly, doubly, and
      quadruply N-fused heptaphyrins.
AB  - meso-Heptakis(pentafluorophenyl) heptaphyrin(1.1.1.1.1.1.1) (1) was prepared by a
      stepwise route in 39 % yield and its unique N-fusion reaction (NFR) sequence has
      been revealed; this reaction leads to singly-, doubly-, and quadruply N-fused
      heptaphyrins (4, 5, and 6) in good yields. These transformations are facilitated
      by the inherent conformational distortion of 1 as well as the distorted, folded
      conformations of N-fused heptaphyrins 4 and 5. The proximate arrangement of the
      three pyrrole units in 6 allowed for the formation of the tripyrrolylboron(III)
      complexes 7, 8, and 9 with unique coordination features. Molecules 1, 5, and 9
      were structurally characterized by X-ray crystallography. In addition, the boron
      complexes 7, 8, and 9 displayed weak but distinct fluorescence in the near
      infrared region.

PMID- 16991190
TI  - Luminescent Pt(II)(bipyridyl)(diacetylide) chromophores with pendant binding
      sites as energy donors for sensitised near-infrared emission from lanthanides:
      structures and photophysics of Pt(II)/Ln(III) assemblies.
AB  - The complexes [Pt(bipy){CC-(4-pyridyl)}(2)] (1) and [Pt(tBu(2)bipy){CC-(4
      pyridyl)}(2)] (2) and [Pt(tBu(2)-bipy)(CC-phen)(2)] (3) all contain a
      Pt(bipy)(diacetylide) core with pendant 4-pyridyl (1 and 2) or phenanthroline (3)
      units which can be coordinated to {Ln(diketonate)(3)} fragments (Ln = a
      lanthanide) to make covalently-linked Pt(II)/Ln(III) polynuclear assemblies in
      which the Pt(II) chromophore, absorbing in the visible region, can be used to
      sensitise near-infrared luminescence from the Ln(III) centres. For 1 and 2 one
      dimensional coordination polymers [1Ln(tta)(3)](infinity) and
      [2Ln(hfac)(3)](infinity) are formed, whereas 3 forms trinuclear adducts
      [3{Ln(hfac)(3)}(2)] (tta=anion of thenoyl-trifluoroacetone; hfac=anion of
      hexafluoroacetylacetone). Complexes 1-3 show typical Pt(II)-based (3)MLCT
      luminescence in solution at approximately 510 nm, but in the coordination
      polymers [1Ln(tta)(3)](infinity) and [2Ln(hfac)(3)](infinity) the presence of
      stacked pairs of Pt(II) units with short PtPt distances means that the
      chromophores have (3)MMLCT character and emit at lower energy ( approximately 630
      nm). Photophysical studies in solution and in the solid state show that the
      (3)MMLCT luminescence in [1Ln(tta)(3)](infinity) and [2Ln(hfac)(3)](infinity) in
      the solid state, and the (3)MLCT emission of [3{Ln(hfac)(3)}(2)] in solution and
      the solid state, is quenched by Pt-->Ln energy transfer when the lanthanide has
      low-energy f-f excited states which can act as energy acceptors (Ln=Yb, Nd, Er,
      Pr). This results in sensitised near-infrared luminescence from the Ln(III)
      units. The extent of quenching of the Pt(II)-based emission, and the Pt-->Ln
      energy-transfer rates, can vary over a wide range according to how effective each
      Ln(III) ion is at acting as an energy acceptor, with Yb(III) usually providing
      the least quenching (slowest Pt-->Ln energy transfer) and either Nd(III) or
      Er(III) providing the most (fastest Pt-->Ln energy transfer) according to which
      one has the best overlap of its f-f absorption manifold with the Pt(II)-based
      luminescence.

PMID- 16991191
TI  - Proteome informatics I: bioinformatics tools for processing experimental data.
AB  - Bioinformatics tools for proteomics, also called proteome informatics tools, span
      today a large panel of very diverse applications ranging from simple tools to
      compare protein amino acid compositions to sophisticated software for large-scale
      protein structure determination. This review considers the available and ready to
      use tools that can help end-users to interpret, validate and generate biological
      information from their experimental data. It concentrates on bioinformatics tools
      for 2-DE analysis, for LC followed by MS analysis, for protein identification by
      PMF, by peptide fragment fingerprinting and by de novo sequencing and for data
      quantitation with MS data. It also discloses initiatives that propose to automate
      the processes of MS analysis and enhance the quality of the obtained results.

PMID- 16991192
TI  - Proteome informatics II: bioinformatics for comparative proteomics.
AB  - The present review attempts to cover the most recent initiatives directed towards
      representing, storing, displaying and processing protein-related data suited to
      undertake "comparative proteomics" studies. Data interpretation is brought into
      focus. Efforts invested into analysing and interpreting experimental data
      increasingly express the need for adding meaning. This trend is perceptible in
      work dedicated to determining ontologies, modelling interaction networks, etc. In
      parallel, technical advances in computer science are spurred by the development
      of the Web and the growing need to channel and understand massive volumes of
      data. Biology benefits from these advances as an application of choice for many
      generic solutions. Some examples of bioinformatics solutions are discussed and
      directions for on-going and future work conclude the review.

PMID- 16991193
TI  - Protein stains for proteomic applications: which, when, why?
AB  - This review recollects literature data on sensitivity and dynamic range for the
      most commonly used colorimetric and fluorescent dyes for general protein
      staining, and summarizes procedures for the most common PTM-specific detection
      methods. It also compiles some important points to be considered in imaging and
      evaluation. In addition to theoretical considerations, examples are provided to
      illustrate differential staining of specific proteins with different detection
      methods. This includes a large body of original data on the comparative
      evaluation of several pre- and post-electrophoresis stains used in parallel on a
      single specimen, horse serum run in 2-DE (IPG-DALT). A number of proteins/protein
      spots are found to be over- or under-revealed with some of the staining
      procedures.

PMID- 16991194
TI  - Strategies for plasma proteomic profiling of cancers.
AB  - Despite a voluminous literature on potential protein biomarkers and a compelling
      need for diagnostic tests based on biomarkers to detect cancers at much earlier,
      more treatable stages, progress has been limited. New methods and new instruments
      for analysis of differences in gene expression, gene methylation, and proteomics
      are being employed to try to accelerate the discovery phase. Given the
      heterogeneity of tumor mechanisms and the limitations of analytical methods, it
      is likely that a variety of strategies will be needed and will be complementary.
      That is the basis of this review of proteomic approaches. This article adopts a
      systems biology view, starting with mRNA transcripts in tumors and cultured tumor
      cells to detect mRNA overexpression, some of which will be correlated with
      protein overexpression. Some of those proteins may be secreted or released into
      proximal biofluids and plasma. Detection of low-abundance tumor proteins in the
      complex and dynamic mixture that is plasma requires combinations of increasingly
      powerful technologies. The biological amplification of protein signals through
      the immune system offers autoantibodies as potential biomarkers. Higher abundance
      proteins, including acute-phase reactants, may have practical value, especially
      if the proteins are modified as part of the cancer processes. Low molecular
      weight proteins, fragments, and peptides may offer complementary biomarkers.
      Promising biomarker candidates must be confirmed in independent studies. Then
      they must be submitted to higher-throughput methods practical for large-scale
      validation studies and, hopefully, for clinical and epidemiological applications.
      Standardized operating procedures for specimen handling, design and use of
      various reference standards, care to avoid bias and confounding, and guidelines
      for reporting findings and contributing datasets should enhance the prospects for
      predictive proteomic profiling of people at risk for cancers.

PMID- 16991195
TI  - Rejuvenating rice proteomics: facts, challenges, and visions.
AB  - Proteomics is progressing at an unprecedented pace, as can be exemplified by the
      progress in model organisms such as yeast, bacteria, and mammals. Proteomics
      research in plants, however, has not progressed at the same pace. Unscrambling of
      the genome sequences of the dicotyledoneous Arabidopsis thaliana (L.) and
      monocotyledoneous rice (Oryza sativa L.) plant species, respectively, has made
      them accessible reference organisms to study plant proteomics. Study of these two
      reference plants is expected to unravel the mystery of plant biology. Rice, a
      critically important food crop on the earth, has been termed a "cornerstone" and
      the "Rosetta stone" for functional genomics of cereal crops. Here, we look at the
      progress in unraveling rice proteomes and present the facts, challenges, and
      vision. The text is divided into two major parts: the first part presents the
      facts and the second part discusses the challenges and vision. The facts include
      the technology and its use in developing proteomes, which have been critically
      and constructively reviewed. The challenges and vision deal with the
      establishment of technologies to exhaustively investigate the protein components
      of a proteome, to generate high-resolution gel-based reference maps, and to give
      rice proteomics a functional dimension by studying PTMs and isolation of
      multiprotein complexes. Finally, we direct a vision on rice proteomics. This is
      our third review in series on rice proteomics, which aims to stimulate an
      objective discussion among rice researchers and to understand the necessity and
      impact of unraveling rice proteomes to their full potential.

PMID- 16991196
TI  - Ions of the interactome: the role of MS in the study of protein interactions in
      proteomics and structural biology.
AB  - The role of MS in the study of protein-protein interactions in solution is
      described from a proteomics perspective, in terms of high-throughput analyses of
      protein complexes in vivo, through to chemical and biochemical treatments ahead
      of MS analysis in the context of complementary experimental approaches in
      structural biology. The use of MS to characterise protein-protein interactions is
      described following the single and tandem affinity purification of protein
      complexes and assemblies of expressed proteins in host cells, the isolation and
      preservation of protein complexes on surfaces and microarrays, and their prior
      treatment with chemical and biochemical probes by hydrogen exchange, radical
      probe, chemical cross-linking, and limited proteolysis. The advantages and
      disadvantages of each of the approaches are presented. These new and emerging
      applications, which further demonstrate the power of MS, continue to ensure that
      the mass spectrometer will remain at the heart of discoveries in proteomics in
      the foreseeable future.

PMID- 16991197
TI  - Plant proteome analysis: a 2004-2006 update.
AB  - Since the appearance of the review entitled "Plant Proteome Analysis" in
      Proteomics in February 2004 (Canovas, F. M., Dumas-Gaudot, E., Recorbert, G.,
      Jorrin, J. et al., Proteomics 2004, 4, 285-298), about 200 original articles
      focusing on plant proteomics have been published. Although this represents less
      than 1% of the global proteomics output during this period, it nevertheless
      reflects an increase in activity over the period 1999-2004. These papers concern
      the proteome of at least 35 plant species but have concentrated mainly on thale
      cress (Arabidopsis thaliana) and rice (Oryza sativa). The scientific objectives
      have ranged from a proteomic analysis of organs, tissues, cell suspensions, or
      subcellular fractions to the study of plant development and response to various
      stresses. A number of contributions have covered PTMs and protein interactions.
      The dominant analytical platform has been 2-DE coupled to MS, but "second
      generation" techniques such as DIGE, multidimensional protein identification
      technology, isotope-coded affinity tags, and stable isotope labeling by amino
      acids in cell culture have begun to make an impact. This review aims to provide
      an update of the contribution of proteomics to plant biology during the period
      2004-2006, and is divided into six sections: introduction, subcellular proteomes,
      plant development, responses to biotic and abiotic stresses, PTMs, and protein
      interactions. The conclusions summarize a view of the major pitfalls and
      challenges of plant proteomics.

PMID- 16991198
TI  - Viral proteomics: a promising approach for understanding JC virus tropism.
AB  - The human polyomavirus JC virus (JCV) is responsible for the CNS demyelination
      observed in cases of progressive multifocal leukoencephalopathy. The JCV
      regulatory region (promoter) is a hypervariable, noncoding, nucleotide sequence
      positioned between the early and late protein-coding regions in the viral genome.
      Selective binding of cellular transcription factors to this promoter region
      participates in the control of viral tropism. Hence, further study of these
      proteins might provide new insights into JCV tropism and associated pathogenesis.
      This review gives an overview of viral proteomics - the study of all proteins
      expressed from the viral gene transcripts, and all the cellular proteins that
      play a role in JCV tropism. It also describes a new biochemical approach for
      studying relevant JCV promoter-binding proteins, which is an anchored-JCV
      transcriptional promoter (ATP) assay. An ATP assay utilizes the product of PCR
      amplified JCV promoter sequences coupled with Sepharose beads in order to capture
      and isolate cellular nuclear proteins with specific promoter-binding affinity for
      analysis. Proteins that bind to JCV-ATPs can be eluted and subjected to proteomic
      analysis. Insights from this approach may improve the understanding of viral and
      cellular parameters that control JCV tropism.

PMID- 16991199
TI  - High resolution proteome/peptidome analysis of body fluids by capillary
      electrophoresis coupled with MS.
AB  - All organisms contain thousands of proteins and peptides in their body fluids. A
      deeper insight into the functional relevance of these polypeptides under
      different physiological and pathophysiological conditions and the discovery of
      specific peptide biomarkers would greatly enhance both diagnosis and therapy of
      specific diseases. Proteomic methods can provide means to accomplish this grand
      medical vision. In this review, we will focus on the potential use of proteome
      analysis for clinical applications, such as disease diagnosis and assessment of
      response to therapy. We focus on CE coupled with MS (CE-MS) and review in detail
      different aspects of CE-MS coupling and the results obtained using CE-MS analysis
      of clinically relevant samples. We also discuss clinical applications of the
      technology for the diagnosis of renal diseases, urogenital cancer, and
      arteriosclerosis as well as monitoring the responses to therapeutic
      interventions.

PMID- 16991200
TI  - Plant phosphoproteomics: a long road ahead.
AB  - Phosphoproteomics can be defined as the comprehensive study of protein
      phosphorylation by identification of the phosphoproteins, exact mapping of the
      phosphorylation sites, quantification of phosphorylation, and eventually,
      revealing their biological function. Its place in today's research is vitally
      important to address the most fundamental question - how the phosphorylation
      events control most, if not all, of the cellular processes in a given organism?
      Despite the immense importance of phosphorylation, the analysis of
      phosphoproteins on a proteome-wide scale remains a formidable challenge.
      Nevertheless, several technologies have been developed, mostly in yeast and
      mammals, to conduct a large-scale phosphoproteomic study. Some of these
      technologies have been successfully applied to plants with a few modifications,
      resulting in documentation of phosphoproteins, phosphorylation site mapping,
      identification of protein kinase substrates, etc. at the global level. In this
      review, we summarize in vitro and in vivo approaches for detection and analysis
      of phosphoproteins including protein kinases and we discuss the importance of
      phosphoproteomics in understanding plant biology. These approaches along with
      bioinformatics will help plant researchers to design and apply suitable
      phosphoproteomic strategies in helping to find answers to their biological
      questions.

PMID- 16991201
TI  - Label-free detection methods for protein microarrays.
AB  - With the growth of the "-omics" such as functional genomics and proteomics, one
      of the foremost challenges in biotechnologies has become the development of novel
      methods to monitor biological process and acquire the information of biomolecular
      interactions in a systematic manner. To fully understand the roles of newly
      discovered genes or proteins, it is necessary to elucidate the functions of these
      molecules in their interaction network. Microarray technology is becoming the
      method of choice for such a task. Although protein microarray can provide a high
      throughput analytical platform for protein profiling and protein-protein
      interaction, most of the current reports are limited to labeled detection using
      fluorescence or radioisotope techniques. These limitations deflate the potential
      of the method and prevent the technology from being adapted in a broader range of
      proteomics applications. In recent years, label-free analytical approaches have
      gone through intensified development and have been coupled successfully with
      protein microarray. In many examples of label-free study, the microarray has not
      only offered the high throughput detection in real time, but also provided
      kinetics information as well as in situ identification. This article reviews the
      most significant label-free detection methods for microarray technology,
      including surface plasmon resonance imaging, atomic force microscope,
      electrochemical impedance spectroscopy and MS and their applications in
      proteomics research.

PMID- 16991202
TI  - The pitfalls of proteomics experiments without the correct use of bioinformatics
      tools.
AB  - The elucidation of the entire genomic sequence of various organisms, from viruses
      to complex metazoans, most recently man, is undoubtedly the greatest triumph of
      molecular biology since the discovery of the DNA double helix. Over the past two
      decades, the focus of molecular biology has gradually moved from genomes to
      proteomes, the intention being to discover the functions of the genes themselves.
      The postgenomic era stimulated the development of new techniques (e.g. 2-DE and
      MS) and bioinformatics tools to identify the functions, reactions, interactions
      and location of the gene products in tissues and/or cells of living organisms.
      Both 2-DE and MS have been very successfully employed to identify proteins
      involved in biological phenomena (e.g. immunity, cancer, host-parasite
      interactions, etc.), although recently, several papers have emphasised the
      pitfalls of 2-DE experiments, especially in relation to experimental design, poor
      statistical treatment and the high rate of 'false positive' results with regard
      to protein identification. In the light of these perceived problems, we review
      the advantages and misuses of bioinformatics tools - from realisation of 2-DE
      gels to the identification of candidate protein spots - and suggest some useful
      avenues to improve the quality of 2-DE experiments. In addition, we present key
      steps which, in our view, need to be to taken into consideration during such
      analyses. Lastly, we present novel biological entities named 'interactomes', and
      the bioinformatics tools developed to analyse the large protein-protein
      interaction networks they form, along with several new perspectives of the field.

PMID- 16991203
TI  - Simultaneous separation of nitrofuran antibiotics and their metabolites by using
      micellar electrokinetic capillary chromatography.
AB  - Mixtures comprising nitrofuran antibiotics (NFA) and nitrofuran metabolites (NFM)
      were resolved for the first time by using MEKC. Sodium deoxycholate (SDC) was
      chosen as the micelle-forming surfactant. Optimization of separation conditions
      was achieved by using a central composite experimental design (CCD) approach.
      Experimental parameters such as concentration ratio of borate to phosphate in the
      buffer, pH of the running electrolyte and voltage were investigated. The effect
      of concentration of the surfactant on resolution was significant. Under optimal
      conditions of 80 mM SDC, pH 9.0, (20 mM borate + 20 mM phosphate) and 16 kV, the
      resolution between eight consecutive peak pairs ranged from 1.9 to 11.8. Due to
      the absence of a UV-active chromophore in the metabolites, they were derivatized
      with 2-nitrobenzaldehyde (2-NBA). In order to mimic a proposed extraction
      procedure for the analysis of both NFA and/or derivatized NFM in a sample,
      aqueous samples (prederivatized with 2-NBA) were extracted by using C(18) SPE
      cartridges. After washing with H(2)O, the cartridges were eluted with a small
      portion of organic solvent with weak elution characteristics to remove excess 2
      NBA (hexane was chosen). Target analytes were then recovered with ACN. Excellent
      reproducibility of migration time (t(mig)) was achieved for all analytes using
      the developed MECC approach, with absolute t(mig) <1% RSD and t(mig) ratio <0.2%
      RSD, and peak area ratio was 4% RSD. The LOD for each compound, calculated by
      extrapolating to an S/N of 3, were found to be 0.19-2.0 microg/mL.

PMID- 16991204
TI  - Application of capillary zone electrophoresis with large-volume sample stacking
      to the sensitive determination of sulfonamides in meat and ground water.
AB  - A CZE method with UV-Vis detection has been established and validated for the
      determination of nine sulfonamides: sulfapyridine, sulfamethazine, sulfamerazine,
      sulfamether, sulfadiazine, sulfadimethoxine, sulfamethoxazole,
      sulfachlorpyridazine, and sulfamethizole. Optimum separation was obtained on a
      64.5 cm x 75 microm bubble cell capillary using a buffer containing 45 mM sodium
      phosphate and 10% methanol at pH 7.3, with temperature and voltage of 27 degrees
      C and 25 kV, respectively. p-Aminobenzoic acid was used as an internal standard .
      Taking into account the lack of sensitivity of the UV-Vis detection, the
      application of an on-line preconcentration methodology, such as large-volume
      sample stacking with polarity switching has been proposed. This procedure
      combined with a solvent extraction/SPE method applied for off-line
      preconcentration and cleanup provides a significant improvement in the LODs,
      ranging from 2.59 to 22.95 mug/L for the studied compounds; the quantification of
      these residues being possible below the levels established by EU legislation in
      animal food products, such as meat. Satisfactory recoveries were also obtained in
      the analysis of these compounds in ground water.

PMID- 16991205
TI  - Mass distribution and focusing properties of carrier ampholytes for isoelectric
      focusing: I. Novel and unexpected results.
AB  - In an attempt to prepare quasi-isoelectric buffers as BGEs for CE, carrier
      ampholytes (CAs) (Ampholine, pH 7-9; Servalyt, pH 7-9; Bio-Lyte, pH 8-10 and
      Pharmalyte, pH 8-10.5) have been subdivided with the Rotofor into 20 fractions,
      of ca. 0.1 pH unit span, whose composition has been studied by CZE-MS. The
      results have allowed identifying the number of different molecular mass compounds
      present in every commercial brand, as well as the number of isoforms (having
      identical mass, but representing positional isomers) associated with a given M(r)
      value. Ampholine is composed of 29 species, for a total of 85 different isoforms;
      Bio-Lyte is made of 43 compounds, for a total of 136 isoforms; Pharmalyte
      comprises 58 different M(r) chemicals, for a total of 102 isoforms and Servalyt
      is constituted by 65 species, for a total of 306 compounds (all of these values
      to be considered as minimum numbers, as detected by the present methodology).
      Surprisingly, and contrary to theory, a very large proportion (up to 70%) of
      these species are 'poor carrier ampholytes', in that they are unable to focus and
      are evenly distributed along the generated pH gradient in the electric field.
      Paradoxically, the pH gradient is created and sustained by the minority of
      species (30% for three brands, up to 50% for Pharmalyte) that appear to focus at
      their pI position into reasonably sharp zones. Even in the narrowest pI fraction,
      up to 20 different compounds can be detected. It is concluded that very few
      amines with different useful pK values are utilized for the synthesis and that a
      new generation of CAs with a more diversified population of amines with proper pK
      values within the given pH intervals should be sought. Ampholine, the poorest of
      the commercial brands, appears to be still made with the original synthesis
      devised by Vesterberg, i.e. by reacting a concoction of oligoamines with
      alpha,beta-unsaturated acids.

PMID- 16991206
TI  - Discontinuous native protein gel electrophoresis.
AB  - Analysis of the oligomeric state of a native protein usually requires analytical
      ultracentrifugation or repeated gel filtration to calculate the protein's size.
      We have developed a discontinuous native protein gel electrophoresis system that
      allows the separation of even basic proteins according to their size, oligomeric
      state, and shape. This gel system combines the addition of negative charges to
      the proteins by Serva Blue G with a discontinuous buffer system and gradient
      gels. As in SDS-PAGE, chloride constitutes the high mobility anion in the gel and
      anode buffer. However, for sample focusing this system employs histidine instead
      of glycine as the slow dipolar ion following from the cathode buffer to improve
      migration of basic proteins. In addition, proteins run into gel pores
      corresponding to their size and shape in the gradient gel. Using this gel system,
      we show that the polypyrimidine tract-binding protein (PTB) is a monomer.

PMID- 16991207
TI  - Kinetic study of paracetamol on prolidase activity in erythrocytes by capillary
      electrophoresis with Ru(bpy)(3) (2+) electrochemiluminescence detection.
AB  - We explored the CE with (bpy) (2+) (3) electrochemiluminescence detection for the
      kinetic study of drug-enzyme interaction. Effects of four nonsteroidal anti
      inflammatory drugs including aspirin, paracetamol, sodium salicylate and
      phenacetin on prolidase (PLD) activity in erythrocytes were investigated. Aspirin
      enhanced PLD activity whereas the other three had inhibiting effects. This may
      reveal their different effects on the collagen biosynthesis and catabolism that
      influence tumor invasiveness. Kinetic study of paracetamol on PLD showed that the
      value of Michaelis constant K(m) for PLD was 1.23 mM. The mechanism of PLD
      inhibition by paracetamol is noncompetitive inhibition, and the inhibitor
      constant K(i) value obtained in our research was 9.73 x 10(3) microg/L.

PMID- 16991208
TI  - The market for efficiency analysis of health care organisations.

PMID- 16991209
TI  - VIP, PACAP, and related peptides: from gene to therapy. Proceedings of the 7th
      International Symposium on VIP, PACAP, and Related Peptides. September 11-14,
      2005. Rouen, France.

PMID- 16991210
TI  - Trends in detection of new cases. Papers presented at a workshop held during the
      Indian Association of Leprologists Conference. Winter, 2005. Agra, India.

PMID- 16991212
TI  - Worries over conservation plans.

PMID- 16991211
TI  - Funding hopes for a sea change.

PMID- 16991213
TI  - Nitric oxide: basic regulations and pharmacological interventions. Abstracts from
      a symposium, September 21-24, 2005. Tucepi, Croatia.

PMID- 16991214
TI  - Trudy Mackay. Interview.

PMID- 16991215
TI  - Proceedings and abstracts from the 19th International Congress on Thrombosis. May
      14-18, 2006. Tel-Aviv, Israel.

PMID- 16991216
TI  - Free access to pharmacovigilance data.

PMID- 16991217
TI  - Glitazones and macular oedema.

PMID- 16991218
TI  - Glucosamine allergy.

PMID- 16991220
TI  - EUROTOX 2006/6 CTDC Congress. Abstracts of the 43rd Congress of the European
      Societies of Toxicology and the 6th Congress of Toxicology in Developing
      Countries, Cavtat, Croatia, 20-24 September 2006.

PMID- 16991219
TI  - Telithromycin: severe hepatitis.

PMID- 16991221
TI  - Translation of basic insights into clinical practice. Abstracts from the 3rd
      Annual Symposium of the American Heart Association Council on Basic
      Cardiovascular Sciences. July 31 - August 3, 2006. Keystone, Colorado, USA.

PMID- 16991222
TI  - [Role of syndromic surveillance in the reaction of sudden public health events].

PMID- 16991223
TI  - [Association between obesity and genetic polymorphism].

PMID- 16991224
TI  - [Acute infection by human immunodeficiency virus (HIV) in a primary care team].

PMID- 16991225
TI  - [Should we ask pediatricians recommend follow-ups for children between the ages
      of 1 and 3?].

PMID- 16991226
TI  - [Care of the terminal patient: as seen by the family doctor].

PMID- 16991227
TI  - AZ: Agency RN falls on floor and sues hospital: agency nurse's suit against
      hospital barred.

PMID- 16991228
TI  - Stepping up: nurse leaders champion reform.

PMID- 16991229
TI  - Etanercept and recalcitrant acrodermatitis continua of Hallopeau.

PMID- 16991230
TI  - Aged care must move beyond political point score.

PMID- 16991231
TI  - Medication course gets a tick.

PMID- 16991232
TI  - UK experience confirms the worst of Howard's IR agenda.

PMID- 16991234
TI  - An Account of the Anatomy and Physiology of Batrachian Lymph-Hearts (mainly
      Bibliographical).

PMID- 16991233
TI  - The fertility clinic nurse and lifestyle education.

PMID- 16991235
TI  - Does the Apex of the Heart contract automatically?

PMID- 16991237
TI  - Contributions to the Physiology of Batrachian Lymph-Hearts.

PMID- 16991236
TI  - Preliminary Note of further Investigations upon the Vaso-motor Nerves of Striated
      Muscle.

PMID- 16991239
TI  - Note on 'Fechner's Law'.

PMID- 16991238
TI  - Concerning the Effects on the Heart of Alternate Stimulation of the Vagi.

PMID- 16991240
TI  - On Hyperplasia of the Muscular Tissue of the Lungs.

PMID- 16991242
TI  - Concerning the Effects on Frogs of Arrest of the Circulation, and an Explanation
      of the Action of Potash Salts on the Animal Body.

PMID- 16991241
TI  - Some Remarks on the Formation of Ferment in the Sub-maxillary Gland of the
      Rabbit.

PMID- 16991243
TI  - On the Physiology of the Salivary Secretion: Part I. The Influence of the Chorda
      Tympani and Sympathetic Nerves upon the Secretion of the Sub-maxillary Gland of
      the Cat.

PMID- 16991244
TI  - Changes of the Globular Richness of Human Blood.

PMID- 16991245
TI  - Estimation of Lime in the Shell and in the Interior of the Egg, before and after
      Incubation.

PMID- 16991246
TI  - On the Physiological Action of Narcissia, an Alkaloid obtained from the Bulb of
      the common Daffodil (Narcissus Pseudo-Narcissus).

PMID- 16991247
TI  - On the Influences which Modify the Work of the Heart.

PMID- 16991248
TI  - On the Stable Colours of the Retina.

PMID- 16991249
TI  - The Normal Respiratory Movements of the Frog, Influence upon its Respiratory
      Centre of Stimulation of the Optic Lobes.

PMID- 16991251
TI  - Addition to the Article "On the Stable Colours of the Retina".

PMID- 16991250
TI  - An Account of two Experiments illustrating the Effects of Starvation, with and
      without severe Labour, on the Elimination of Urea from the Body.

PMID- 16991252
TI  - Sweat Centres: the Effect of Muscarin and Atropin on them.

PMID- 16991253
TI  - A Report on Prof. L. Hermann's recent Researches on the Electro-motive Properties
      of Muscle.

PMID- 16991254
TI  - The Action of Arseniate of Soda and Arsenious Acid on Frogs.

PMID- 16991255
TI  - Concerning the Action of Aconitia on the Nervous and Muscular System of Frogs.

PMID- 16991256
TI  - The Action of Tartar Emetic, Hydrocyanic Acid and Veratria on the Animal Body.

PMID- 16991257
TI  - The Structural Changes in the Epidermis of the Frog, brought about by Poisoning
      with Arsenic and with Antimony.

PMID- 16991258
TI  - On the Structural Changes which are produced in the Liver under the Influence of
      the Salts of Vanadium.

PMID- 16991259
TI  - Further Researches on the Vasomotor Nerves of Ordinary Muscles.

PMID- 16991260
TI  - The Function of the Epiglottis in Deglutition and Phonation.

PMID- 16991261
TI  - The Development and Regeneration of the Gastric Glandular Epithelium during
      Foetal Life and after Birth.

PMID- 16991263
TI  - On the Physiology of the Salivary Secretion: Part II. On the Mutual Antagonism of
      Atropin and Pilocarpin, having especial reference to their relations in the Sub
      maxillary Gland of the Cat.

PMID- 16991262
TI  - On the Epithelium of the Cornea.

PMID- 16991264
TI  - The Influence of Stimulation of the Midbrain upon the Respiratory Rhythm of the
      Mammal.

PMID- 16991265
TI  - On Pituri.

PMID- 16991266
TI  - The Genesis of Tetanus.

PMID- 16991267
TI  - On the so-called "Initial Contraction".

PMID- 16991268
TI  - The Physiological Action of Heat.

PMID- 16991269
TI  - ON A NEW METHOD FOR DETERMINING THE PRESENCE OF SENSORY NERVES.

PMID- 16991270
TI  - A New Microtome.

PMID- 16991271
TI  - On the Respiratory Function of the Internal Intercostal Muscles.

PMID- 16991272
TI  - On the Formation of Hypoxanthine from Albumin.

PMID- 16991273
TI  - Observations of Visual Purple in the Human Eye.

PMID- 16991275
TI  - The Form of the Pulse-Wave: As studied in the Carotid of the Rabbit.

PMID- 16991274
TI  - Observations on the Physiology of the Spinal Cord.

PMID- 16991276
TI  - Pharyngeal Respiration.

PMID- 16991277
TI  - On Absorption without Circulation.

PMID- 16991278
TI  - On Protagon.

PMID- 16991279
TI  - On a Few Further Experiments with Pituria.

PMID- 16991280
TI  - On the Antagonism between Pilocarpine and Extract of Amanita Muscaria.

PMID- 16991281
TI  - On some Old and New Experiments on the Fibrin-Ferment.

PMID- 16991283
TI  - On the Effect of the Respiratory Movements on the Pulmonary Circulation.

PMID- 16991282
TI  - On the Effect of two Succeeding Stimuli upon Muscular Contraction.

PMID- 16991286
TI  - Description of a Modified Pendulum-Myograph.

PMID- 16991284
TI  - On the so-called Heat-Dyspnoea.

PMID- 16991285
TI  - Physiological Apparatus in use at the Harvard Medical School.

PMID- 16991287
TI  - On the Reliability of Marey's Tambour in Experiments requiring Accurate Notations
      of Time.

PMID- 16991288
TI  - Some Notes on the Physiology of the Nervous System of the Freshwater Crayfish
      (Astacus fluviatilis).

PMID- 16991289
TI  - Some Experiments as to the Influence of the Surrounding Temperature on the
      Discharge of Carbonic Acid in the Dog.

PMID- 16991290
TI  - On The Relative Paralysing Action of Atropia and Pilocarpinf Heart.

PMID- 16991291
TI  - Concerning the Action of Common Salt, Sulphate of Atropia, Bromide of Conia and
      Sulphate of Nicotine on Muscular Irritability.

PMID- 16991292
TI  - On the Changes in Serous Glands during Secretion.

PMID- 16991293
TI  - On the Changes in Pepsin-forming Glands during Secretion.

PMID- 16991294
TI  - The Physiological Action of Heat: Part II.

PMID- 16991295
TI  - The Blood-Pressure and its Variations in the Arterioles, Capillaries and Smaller
      Veins.

PMID- 16991296
TI  - The Constitution and Relations of Bone Lamellae, Lacunae, and Canaliculi, and
      some Effects of Trypsin Digestion on Bone.

PMID- 16991297
TI  - On the Time-Relations of the Excitatory Process in the Ventricle of the Heart of
      the Frog.

PMID- 16991298
TI  - On the Antagonisms of Aconitia on the Frog's Heart.

PMID- 16991299
TI  - The Dilatation of the Pupil as an Index of the Path of the Sensory Impulses in
      the Spinal Cord.

PMID- 16991300
TI  - Note on the Action upon the Circulation of certain Volatile Oils.

PMID- 16991301
TI  - Some further Observations on Heat-Dyspnoea.

PMID- 16991303
TI  - The Influence of Quinine upon the Reflex-Excitability of the Spinal Cord.

PMID- 16991302
TI  - On the Antagonism of Poisons.

PMID- 16991304
TI  - Note of Observations on the Rate of Propagation of the Arterial Pulse-Wave.

PMID- 16991305
TI  - On the Tonicity of the Heart and Blood Vessels.

PMID- 16991306
TI  - A Contribution to the Study of Inflammation as Illustrated by Induced Keratitis.

PMID- 16991307
TI  - On the Physiology of the Retinal Epithelium.

PMID- 16991308
TI  - Concerning the Influence of Season and of Temperature on the Action and on the
      Antagonisms of Drugs.

PMID- 16991309
TI  - The Elastic Properties of the Arterial Wall.

PMID- 16991311
TI  - Notes on Inhibition.

PMID- 16991310
TI  - On Crossed Hyperaesthesia.

PMID- 16991312
TI  - On the Proteid Substances contained in the Seeds of Plants.

PMID- 16991314
TI  - On the Polar Effects upon Nerves of Weak Induction Currents.

PMID- 16991313
TI  - Observations on the Mean Pressure, and the Characters of the Pulse-wave in the
      Coronary Arteries of the Heart.

PMID- 16991315
TI  - Notes on the Temperature of Heat-Coagulation of certain of the Proteid Substances
      of the Blood.

PMID- 16991317
TI  - Regarding the Action of Hydrate of Soda, Hydrate of Ammonia, and Hydrate of
      Potash on the Ventricle of the Frog's Heart.

PMID- 16991316
TI  - On the Existence of Bacteria, or their Antecedents, in Healthy Tissues.

PMID- 16991318
TI  - The Physiology and Pathology of the Spleen: First communication.

PMID- 16991319
TI  - A Case of Loss of Taste from Disease of the Fifth Nerve.

PMID- 16991320
TI  - A Comparison of Sight and Touch.

PMID- 16991321
TI  - On the Destruction of Ferments in the Alimentary Canal.

PMID- 16991322
TI  - On the Histology of the Mammalian Gastric Glands and the Relation of Pepsin to
      the Granules of the Chief-Cells.

PMID- 16991323
TI  - A Simple Method of Demonstrating the Alkaline Reaction of the Blood.

PMID- 16991324
TI  - Note on the Production of the Second Heart-Sound.

PMID- 16991325
TI  - Optical Illusions of Motion.

PMID- 16991326
TI  - Reflex Movements of the Frog under the Influence of Strychnia.

PMID- 16991327
TI  - A Contribution to our Knowledge of the Action of Certain Drugs upon Bodily
      Temperature.

PMID- 16991328
TI  - Influence of Peptones and Certain Inorganic Salts on the Diastatic Action of
      Saliva.

PMID- 16991329
TI  - On Cerebral Localization.

PMID- 16991330
TI  - The Physiological Action of Methylkyanethine.

PMID- 16991331
TI  - On the Influence of Variations of Intra-cardiac Pressure upon the Inhibitory
      Action of the Vagus Nerve.

PMID- 16991332
TI  - Preliminary Observations on the Innervation of the Heart of the Tortoise.

PMID- 16991333
TI  - Concerning the Influence exerted by each of the Constituents of the Blood on the
      Contraction of the Ventricle.

PMID- 16991334
TI  - Influence of Heat and Cold upon Muscles poisoned by Veratria.

PMID- 16991335
TI  - On certain conditions which influence the Amylolytic Action of Saliva.

PMID- 16991337
TI  - On the Electrical Phenomena of the Excitatory Process in the Heart of the Frog
      and of the Tortoise, as investigated Photographically.

PMID- 16991336
TI  - A further Contribution regarding the influence of the different Constituents of
      the Blood on the Contraction of the Heart.

PMID- 16991338
TI  - Experiments upon the Ears of Fishes with reference to the Function of
      Equilibrium.

PMID- 16991340
TI  - On the Action of Digitalis.

PMID- 16991339
TI  - Of the Influence of certain Drugs on the Period of Diminished Excitability.

PMID- 16991341
TI  - On the Coagulation of the Blood.

PMID- 16991342
TI  - An Investigation regarding the Action of Rubidium and Caesium Salts compared with
      the Action of Potassium Salts on the Ventricle of the Frog's Heart.

PMID- 16991343
TI  - Some Notes on the Fibrin-Ferment.

PMID- 16991344
TI  - PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY. December 13, 1883.

PMID- 16991345
TI  - Description of a Double Cardiograph for the Frog's Heart.

PMID- 16991346
TI  - An examination of some controverted points of the Physiology of Voice, especially
      the Registers of the Singing Voice and the Falsetto.

PMID- 16991347
TI  - A method and apparatus for obtaining Graphic Records of various kinds of
      Movements of the Hand and its parts, and enumerating such movements and their
      combinations.

PMID- 16991348
TI  - The Influence of Digitaline on the Work of the Heart and on the Flow through the
      Blood-vessels.

PMID- 16991349
TI  - On the Relation between the Active Phases of Contraction and the Latent Period of
      Skeletal Muscle.

PMID- 16991350
TI  - A third contribution regarding the Influence of the Inorganic Constituents of the
      Blood on the Ventricular Contraction.

PMID- 16991351
TI  - Further observations on the Coagulation of the Blood.

PMID- 16991352
TI  - On the Innervation of the Heart, with especial reference to the Heart of the
      Tortoise.

PMID- 16991353
TI  - Report on the Cortical Areas removed from the Brain of a Dog, and from the Brain
      of a Monkey.

PMID- 16991354
TI  - The Structure of the Dog's Brain.

PMID- 16991355
TI  - Report on the Parts Destroyed on the Right Side of the Brain of the Dog operated
      on by Prof. GOLTZ.

PMID- 16991356
TI  - Report on the Parts Destroyed on the Left Side of the Brain of the Dog operated
      on by Prof. GOLTZ.

PMID- 16991358
TI  - The Bacteria of Swine Plague.

PMID- 16991357
TI  - Report on the Lesions, Primary and Secondary, in the Brain and Spinal Cord of the
      Macacque Monkey exhibited by Professors FERRIER and YEO.

PMID- 16991359
TI  - On Rhythmic Contraction of the Capillaries in Man.

PMID- 16991361
TI  - On the connection between Physiological Action and Chemical Constitution.

PMID- 16991360
TI  - Physiological Action of Condurango.

PMID- 16991362
TI  - Note on the Action of Digitalis: A Reply to Dr BLAKE.

PMID- 16991363
TI  - On the Augmentor (Accelerator) Nerves of the Heart of Cold-blooded Animals.

PMID- 16991364
TI  - A Note on the Composition of Human Bile obtained from a Fistula.

PMID- 16991365
TI  - On the Physiological Action of the Salts of Potassium Rubidium and Caesium.

PMID- 16991367
TI  - On the Circulation of the Blood-Corpuscles considered from a Physical Basis.

PMID- 16991368
TI  - On certain Constituents of the eggs of the Common Frog.

PMID- 16991366
TI  - Secondary Degeneration of Nerve Tracts following removal of the Cortex of the
      Cerebrum in the Dog.

PMID- 16991369
TI  - Concerning the Influence of Saline Media on Fish, etc.

PMID- 16991370
TI  - A method of Recording changes of Volume by means of Photography and its
      application to the Plethysmographic record of the normal Frog-Heart.

PMID- 16991371
TI  - The Piston Recorder; an Apparatus for Recording and Measuring the changes of
      Volume of the Contracting Frog's Heart.

PMID- 16991372
TI  - On the Physiological effects of Light which enters the Eye through the Sclerotic
      Coat.

PMID- 16991373
TI  - Note upon Antipyretic Studies.

PMID- 16991374
TI  - On the Temperature Sense. A contribution to the Physiology of the Skin as an
      Organ of Sense.

PMID- 16991375
TI  - The Proteids of Serum.

PMID- 16991376
TI  - Observations of the Gastric Glands of the Pig.

PMID- 16991378
TI  - Papain-Digestion.

PMID- 16991377
TI  - Haematin Compounds.

PMID- 16991380
TI  - On the Comparison of the Concentrations of Solutions of Different Strength of the
      same absorbing Substance.

PMID- 16991379
TI  - The Secretion of Oxalic Acid in the Dog under a varying Diet.

PMID- 16991381
TI  - On the Mutual Antagonism between Lime and Potash Salts, in Toxic Doses.

PMID- 16991382
TI  - The Behaviour of the Red Blood-corpuscles when shaken with Indifferent
      Substances.

PMID- 16991383
TI  - On the Cardiac Rhythm of Invertebrata.

PMID- 16991384
TI  - Some Experiments on the Liver Ferment.

PMID- 16991385
TI  - An Experimental Investigation showing that Veratria is similar to Lime Salts in
      many respects as regards their Action on the Ventricle, also showing that
      Veratria and Lime Salts are reciprocally antagonistic.

PMID- 16991386
TI  - Some Observations on the Influence of the Vagus and Accelerators on the Heart
      etc. of the Turtle.

PMID- 16991387
TI  - On the Anatomy of the Cardiac Nerves in certain Cold-blooded Vertebrates.

PMID- 16991388
TI  - PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY, 1884. No. I. January 19.

PMID- 16991389
TI  - PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY, 1884. No. II. March 15.

PMID- 16991391
TI  - PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY, 1884. No. IV. December 13.

PMID- 16991390
TI  - PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY, 1884. No. III. Oxford. June 7.

PMID- 16991392
TI  - The Minimal Interval at which the summation of two Maximal Stimuli occurs in
      Striated Muscle.

PMID- 16991394
TI  - Some Notes on the Isolation of a Soluble Urea-Ferment from the Torula Ureae.

PMID- 16991393
TI  - Note on the Nature of Nerve-Force.

PMID- 16991395
TI  - On the supposed Catalytic action of Insoluble Reagents.

PMID- 16991397
TI  - A Double Differential Rheotome.

PMID- 16991396
TI  - An Attempt to estimate the Gaseous Interchange of the Frog's Heart by Means of
      the Spectroscope.

PMID- 16991398
TI  - On the Blood of Decapod Crustacea.

PMID- 16991400
TI  - Regarding the influence of the Organic Constituents of the blood on the
      Contractility of the Ventricle.

PMID- 16991399
TI  - The nature of Papain and its Action on Vegetable Proteids.

PMID- 16991401
TI  - On the nature of Glomerular Activity in the Kidney.

PMID- 16991402
TI  - Plethysmographic and vaso-motor experiments with Frogs.

PMID- 16991403
TI  - Some vaso-motor functions of the Spinal Nerves in the Frog.

PMID- 16991404
TI  - Is the Nervous Impulse delayed in the Motor Nerve Terminations?

PMID- 16991405
TI  - Observations on some of the Colouring Matters of Bile and Urine, with especial
      reference to their Origin; and on an Easy Method of procuring Haematin from
      Blood.

PMID- 16991406
TI  - The edible Bird's-nest, or Nest of the Java Swift (Collocalia Nidifica).

PMID- 16991407
TI  - The Velocity of Accommodation.

PMID- 16991408
TI  - On the Physiology of the Salivary Secretion: Part III. The ;Paralytic' Secretion
      of Saliva.

PMID- 16991409
TI  - Proceedings of the Physiological Society 1885. Nos. I., II.

PMID- 16991410
TI  - Note on the cause of the First Sound of the Heart.

PMID- 16991411
TI  - An Experimental Investigation to ascertain the Action of Veratria on a Cardiac
      Contraction.

PMID- 16991412
TI  - Concerning the Action of small quantities of Calcium, Sodium, and Potassium Salts
      upon the Vitality and Function of Contractile Tissue and the Cuticular Cells of
      Fishes.

PMID- 16991413
TI  - A study of the Action of the Depressor Nerve, and a consideration of the Effect
      of Blood-pressure upon the Heart regarded as a Sensory Organ.

PMID- 16991414
TI  - On Secondary and Tertiary Degenerations in the Spinal Cord of the Dog.

PMID- 16991416
TI  - The Innervation of the Heart of the Slider Terrapin (Pseudemys Rugosa).

PMID- 16991415
TI  - On the Structure and Rhythm of the Heart in Fishes, with especial reference to
      the Heart of the Eel.

PMID- 16991417
TI  - Note on the Sound accompanying the Single Contraction of Skeletal Muscle.

PMID- 16991418
TI  - Proceedings of the Physiological Society 1885. No. III.

PMID- 16991419
TI  - On the Structure, Distribution and Function of the Nerves which innervate the
      Visceral and Vascular Systems.

PMID- 16991420
TI  - On the Rhythm of Muscular Response to Volitional Impulses in Man.

PMID- 16991421
TI  - A Further Contribution regarding the Effect of Minute Quantities of Inorganic
      Salts on Organised Structures.

PMID- 16991422
TI  - Note on a Method of obtaining Uric Acid Crystals from the Malpighian Tubes of
      Insects and from the Nephridium of Pulmonate Mollusca.

PMID- 16991423
TI  - Experiments and Considerations on Haemodynamics.

PMID- 16991424
TI  - The Heart of the Fish compared with that of Menobranchus with special reference
      to Reflex Inhibition and independent Cardiac Rhythm.

PMID- 16991425
TI  - Experiments on the character of the Muscular Contractions which are evoked by
      Excitation of the various parts of the Motor Tract.

PMID- 16991426
TI  - Proceedings of the Physiological Society, 1886. No. I.

PMID- 16991427
TI  - Proceedings of the Physiological Society, 1886. No. II.

PMID- 16991428
TI  - Proceedings of the Physiological Society, 1885. No. IV.

PMID- 16991430
TI  - The Distribution of Blood Vessels in the Retinae of Mammals.

PMID- 16991429
TI  - On the Electrical Phenomena accompanying Secretion in the Skin of the Frog.

PMID- 16991431
TI  - On the Presence of Haematoporphyrin in the Integument of certain Invertebrates.

PMID- 16991433
TI  - On Curare.

PMID- 16991432
TI  - On the Digestive Process in some Rhizopods.

PMID- 16991435
TI  - Proceedings of the Physiological Society, 1886. No. III.

PMID- 16991434
TI  - On the Physiological Action of Peptones and Albumoses.

PMID- 16991436
TI  - Further Experiments Regarding the Influence of small quantities of Lime Potassium
      and other Salts on Muscular Tissue.

PMID- 16991438
TI  - The study of Nerve-Muscular Movements; Apparatus for their Automatic Enumeration.

PMID- 16991437
TI  - Description of a Piston Recorder for Air Connections.

PMID- 16991439
TI  - The Liquid Piston Recorder and the Registration of its movements by means of
      Photography.

PMID- 16991440
TI  - On the Blood Proteids of certain Lower Vertebrata.

PMID- 16991441
TI  - Note on the Colouring Matter of the Serum of certain Birds.

PMID- 16991442
TI  - On the Nature and Action of the Venom of Poisonous Snakes: I. The Venom of the
      Indian Cobra (Naja Tripudians).

PMID- 16991443
TI  - On the Nature and Action of the Venom of Poisonous Snakes: II. A Note upon the
      Venom of the Indian Viper (Daboia Russellii).

PMID- 16991444
TI  - On ;Cobric Acid', a so-called Constituent of Cobra Venom.

PMID- 16991446
TI  - Plethysmographic Experiments on the Vaso-motor Nerves of the Limbs.

PMID- 16991447
TI  - The Electrical changes in the Quiescent Cardiac Muscle which accompany
      Stimulation of the Vagus Nerve.

PMID- 16991445
TI  - Pepsinogen and Pepsin.

PMID- 16991449
TI  - A New and Delicate Method for Determining the Local Sensory Action of Drugs.

PMID- 16991448
TI  - Notes on the Urine of the Tortoise with special reference to Uric Acid and Urea.

PMID- 16991450
TI  - On the Variations in the Specific Gravity of the Blood in Health.

PMID- 16991451
TI  - Concerning the Action of Calcium, Potassium, and Sodium Salts upon the Eel's
      Heart and upon the Skeletal Muscles of the Frog.

PMID- 16991452
TI  - Regarding the Action of Lime Potassium and Sodium Salts on Skeletal Muscle.

PMID- 16991453
TI  - Observations upon the Persistent Effects of Division of the Cervical Sympathetic:
      I.

PMID- 16991454
TI  - Proceedings of the Physiological Society, 1887. No. I.

PMID- 16991455
TI  - Further observations on Myohaematin and the Histohaematins.

PMID- 16991456
TI  - On the Histology and Function of the Mammalian Superior Cervical Ganglion.

PMID- 16991457
TI  - On the Physiological action of Ulexin.

PMID- 16991458
TI  - The Electrical Phenomena accompanying the excitation of so-called Secretory and
      Trophic Nerve Fibres in the Salivary Glands of the Dog and Cat.

PMID- 16991459
TI  - On the Influence of Glycerine on the Liver.

PMID- 16991460
TI  - Proceedings of the Physiological Society, 1887. No. II.

PMID- 16991461
TI  - Proceedings of the Physiological Society, 1887. No. III.

PMID- 16991462
TI  - Proceedings of the Physiological Society, 1887. No. IV.

PMID- 16991463
TI  - A Demonstration on Man of Electromotive Changes accompanying the Heart's Beat.

PMID- 16991464
TI  - Observations on the Endocardial Pressure Curve.

PMID- 16991465
TI  - On the Digestive Process in some Rhizopods: Part II.

PMID- 16991466
TI  - Upon the Similarity and Dissimilarity of the behaviour of Cardiac and Skeletal
      Muscle when brought into relation with Solutions containing Sodium, Calcium and
      Potassium Salts.

PMID- 16991467
TI  - Fibrillar Contraction of the Heart.

PMID- 16991468
TI  - The Effect of Pure Alcohol on the reaction time, with a description of a new
      Chronoscope.

PMID- 16991469
TI  - The Tympanic Kymograph: a new Pulse and Blood-pressure Registering Apparatus.

PMID- 16991470
TI  - On certain points connected with the Coagulation of the Blood.

PMID- 16991471
TI  - Note on the Action of Sodium Chloride in dissolving Fibrin.

PMID- 16991473
TI  - On the Haematoporphyrin of Solecurtus Strigillatus.

PMID- 16991472
TI  - The Secretion of the Gall Bladder.

PMID- 16991474
TI  - The Differential Action of Brucine and of Strychnine.

PMID- 16991475
TI  - On the Action of Muscarin upon the Heart, and on the Electrical Changes in the
      non-beating Cardiac Muscle brought about by Stimulation of the Inhibitory and
      Augmentor Nerves.

PMID- 16991476
TI  - On the action of certain Drugs on the circulation and secretion of the Kidney.

PMID- 16991477
TI  - On Muscle-Plasma.

PMID- 16991478
TI  - Experiments on the Preventive Inoculation of Rattlesnake Venom.

PMID- 16991479
TI  - Variations in the Excretion of Uric Acid produced by administration of Acids and
      Alkalies.

PMID- 16991480
TI  - Pyrexial Agents, Albumose, Peptone and Neurin.

PMID- 16991481
TI  - Proceedings of the Physiological Society, 1887. No. V.

PMID- 16991482
TI  - On the Chromatology of some British Sponges.

PMID- 16991483
TI  - The Effect of Stimulation on the Polarisation of Nerve.

PMID- 16991484
TI  - On the Rhythm of Muscular Response to Volitional Impulses in Man.

PMID- 16991485
TI  - Proceedings of the Physiological Society, 1888. No. I.

PMID- 16991486
TI  - Proceedings of the Physiological Society, Dec. 17, 1887. No. VI.

PMID- 16991487
TI  - The Elimination of Aromatic Bodies in Fever.

PMID- 16991488
TI  - On the Relations of Micro-organisms to Pancreatic (Proteolytic) Digestion.

PMID- 16991489
TI  - Note on the Elasticity-Curve of Animal Tissues.

PMID- 16991490
TI  - On the Nature of Fibrin-Ferment.

PMID- 16991491
TI  - Some points in the Physiology of Gland Nerves.

PMID- 16991492
TI  - On the Circumstances which modify the Action of Caffeine and Theine upon
      Voluntary Muscle.

PMID- 16991493
TI  - On the Electrical Organ of the Skate.

PMID- 16991494
TI  - On the Rhythm of the Mammalian Heart.

PMID- 16991495
TI  - Further Researches on the Apparent Change produced by Stimulation in the
      Polarisation of Nerve.

PMID- 16991496
TI  - On the Physiology of the Salivary Secretion.

PMID- 16991497
TI  - The Physiological Action of Borneol. A Contribution to the Pharmacology of the
      Camphor Group.

PMID- 16991498
TI  - A Note on the Cause of the Failure of very rapid Electrical Stimulation to
      produce Tetanus in Muscle.

PMID- 16991500
TI  - Proceedings of the Physiological Society, 1888. No. II.

PMID- 16991499
TI  - An Experimental Investigation of Strychnine Poisoning.

PMID- 16991501
TI  - Proceedings of the Physiological Society, 1888. No. III.

PMID- 16991502
TI  - On Digestion in Hydra, with some Observations on the Structure of the Endoderm.

PMID- 16991503
TI  - On the Phenomena of inhibition in the Mammalian Heart.

PMID- 16991505
TI  - Proceedings of the Physiological Society, 1888. No. IV.

PMID- 16991504
TI  - On the Normal Duration and Significance of the "Latent Period of Excitation" in
      Muscle-contraction.

PMID- 16991506
TI  - Potassium accumulation in muscle and associated changes.

PMID- 16991507
TI  - The influence of anterior pituitary extracts on the insulin content of the
      pancreas of the hypophysectomized rat.

PMID- 16991508
TI  - The antagonism between insulin and posterior lobe pituitary extract.

PMID- 16991509
TI  - On the permeability change of stimulated nerve.

PMID- 16991510
TI  - The pharmacological actions of morphothebaine-dimethylether.

PMID- 16991511
TI  - The influence of secretin on pancreatic secretion in the cat.

PMID- 16991512
TI  - The haemopoietic activity of mammalian livers.

PMID- 16991514
TI  - The effect of insulin administration on the insulin content of the pancreas.

PMID- 16991513
TI  - Differentiation of an (amphibian) water balance principle from the antidiuretic
      principle of the posterior pituitary gland.

PMID- 16991515
TI  - Observations on the relation of histamine to reactive hyperaemia.

PMID- 16991516
TI  - Afferent discharges to the cerebral cortex from peripheral sense organs.

PMID- 16991517
TI  - The gaseous tensions in the brain.

PMID- 16991518
TI  - The effect of oxygen lack on the cerebral circulation.

PMID- 16991519
TI  - The photosensitizing action of buckwheat (Fagopyrum esculentum).

PMID- 16991520
TI  - Further evidence concerning the role of the hypothalamus in the induction of
      ovulation in the rabbit following injections of copper acetate.

PMID- 16991521
TI  - The ratio between antidiuretic and pressor activities of posterior pituitary
      extract subjected to mild hydrolysis.

PMID- 16991523
TI  - The volume of the vascular system, and penetration of sugars from the vascular
      system into the intercellular space.

PMID- 16991522
TI  - A method for estimating the fraction of the volume of a muscle contained in the
      vascular system.

PMID- 16991524
TI  - An investigation of simple methods for diagnosing vitamin a deficiency by
      measurements of dark adaptation.

PMID- 16991525
TI  - The behaviour of the pregnant uterus of the guinea pig.

PMID- 16991526
TI  - A quantitative method of assay for thrombin and prothrombin.

PMID- 16991528
TI  - Strength and size of bone in relation to calcium intake.

PMID- 16991527
TI  - The latency and conduction of potentials in the spinal cord of the frog.

PMID- 16991529
TI  - Abortive impulses at the neuro-muscular junction.

PMID- 16991530
TI  - The glycogen content of the frog's heart.

PMID- 16991531
TI  - Observations bearing on synaptic transmission by acetylcholine in the spinal
      cord.

PMID- 16991532
TI  - A note on interaction between nerve fibres.

PMID- 16991533
TI  - The assimilation of radio-active phosphorus deficiency in rats.

PMID- 16991534
TI  - Glycogen and adipose tissue.

PMID- 16991535
TI  - Ovulation in the rabbit after destruction of the greater superficial petrosal
      nerves.

PMID- 16991536
TI  - The action of curare on the respiratory centre.

PMID- 16991537
TI  - The influence of a deficiency of vitamin B(1) and of riboflavin on the
      reproduction of the rat.

PMID- 16991538
TI  - Urea formation in the isolated perfused liver of the rat.

PMID- 16991539
TI  - Olfactory reactions in the brain of the hedgehog.

PMID- 16991540
TI  - Observations on the properties of S-methyl iso-thiourea sulphate, with particular
      reference to the circulatory effects.

PMID- 16991541
TI  - The compensatory mechanism of the splanchnic circulation during changes of
      posture.

PMID- 16991542
TI  - The effect of hypertonic glucose solutions on the inflow of normal saline
      solution into the subarachnoid space of the dog.

PMID- 16991544
TI  - A method of conducting a biological assay on a preparation giving repeated graded
      responses illustrated by the estimation of histamine.

PMID- 16991543
TI  - The effect of partial pancreatectomy on the concentration of insulin in the
      pancreatic remnant.

PMID- 16991545
TI  - The effect of sodium and calcium on the toxicity of potassium in mice.

PMID- 16991546
TI  - The effect of insulin and anterior pituitary extract on the insulin content of
      the pancreas and the histology of the islets.

PMID- 16991547
TI  - On the influence of weak electric currents and electrically charged surfaces on
      blood coagulation.

PMID- 16991548
TI  - Variations in the water, fat, glycogen and iodine of the flesh of oysters (Ostrea
      virginica) during hibernation and storage at 4 degrees C.

PMID- 16991549
TI  - Mineral metabolism of healthy adults on white and brown bread dietaries.

PMID- 16991550
TI  - Diffusion relations of urea, inulin and chloride in some mammalian tissues.

PMID- 16991552
TI  - The diuretic action of alcohol in man.

PMID- 16991551
TI  - The effects of drugs, sugar and allied substances on the isolated small intestine
      of the rabbit.

PMID- 16991553
TI  - Effects of trimethylamine on growth and sexual development in the rat.

PMID- 16991554
TI  - The cholinergic nature of the nerves to the electric organ of the Torpedo
      (Torpedo marmorata).

PMID- 16991555
TI  - The determination of plasma volume by the Evans blue method.

PMID- 16991556
TI  - The interrelation of prostigmine, adrenaline and ephedrine in skeletal muscle.

PMID- 16991557
TI  - The action of the oxytocic hormone of the pituitary gland on urine secretion.

PMID- 16991558
TI  - The effect of histidine on histamine shock.

PMID- 16991559
TI  - Factors affecting bicarbonate content, free CO(2) and pH of urine.

PMID- 16991560
TI  - The haemolytic action of potassium salts.

PMID- 16991561
TI  - Preparation and some properties of hypertensin (angiotonin).

PMID- 16991562
TI  - An action of adrenaline on transmission in sympathetic ganglia, which may play a
      part in shock.

PMID- 16991563
TI  - Mineral metabolism on dephytinized bread.

PMID- 16991565
TI  - The posterior pituitary principles of a species of reptile (Tropidonotus natrix)
      with some remarks on the comparative physiology of the posterior pituitary gland
      generally.

PMID- 16991564
TI  - The osmotic pressure of foetal horse-serum albumin.

PMID- 16991566
TI  - The effect of graded doses of vitamin C upon the regeneration of bone in guinea
      pigs on a scorbutic diet.

PMID- 16991567
TI  - The activity of l(-)-dopa decarboxylase.

PMID- 16991568
TI  - The significance of urinary calcium, magnesium and phosphorus.

PMID- 16991569
TI  - The effect of anaesthesia on the adrenaline content of the suprarenal glands.

PMID- 16991570
TI  - The effect of variations in the subarachnoid pressure on the venous pressure in
      the superior longitudinal sinus and in the torcular of the dog.

PMID- 16991571
TI  - Acceleration of the heart by the vagus in cats after complete sympathectomy.

PMID- 16991572
TI  - Pulmonary circulation times before and after functional closure of the ductus
      arteriosus.

PMID- 16991574
TI  - Discharges from vestibular receptors in the cat.

PMID- 16991573
TI  - The circulatory effects of some iso-thiourea derivatives, with special reference
      to the sensitization of animals to the pressor action of adrenaline.

PMID- 16991575
TI  - The effect of bone dysplasia (overgrowth) on cranial nerves in vitamin a
      deficient animals.

PMID- 16991576
TI  - Synthesis of acetylcholine in sympathetic ganglia and cholinergic nerves.

PMID- 16991577
TI  - The origin of the inflation and the deflation pulmonary reflexes.

PMID- 16991578
TI  - Oestrogens and acetylcholine.

PMID- 16991579
TI  - Synaptic potentials and transmission in sympathetic ganglion.

PMID- 16991580
TI  - Factors affecting absorption of sodium dl-mandelate from the intestine of cats.

PMID- 16991581
TI  - Recovery of fibre numbers and diameters in the regeneration of peripheral nerves.

PMID- 16991582
TI  - The effect of muscular exercise on the serum cholinesterase level in normal
      adults and in patients with myasthenia gravis.

PMID- 16991583
TI  - Effects of iodoacetic acid, glyceraldehyde and phosphorylated compounds on the
      small intestine of the rabbit.

PMID- 16991584
TI  - Pancreozymin, a stimulant of the secretion of pancreatic enzymes in extracts of
      the small intestine.

PMID- 16991585
TI  - On sympathetic vasoconstrictor tone in human skeletal muscle.

PMID- 16991586
TI  - Histamine in nervous tissue.

PMID- 16991587
TI  - Seasonal and annual changes in the calcium metabolism of man.

PMID- 16991588
TI  - The effect of temperature on blood flow and deep temperature in the human
      forearm.

PMID- 16991589
TI  - Effects of X-rays on acetylcholine solutions showing the dilution and protection
      phenomena, found for enzymes.

PMID- 16991590
TI  - The oxygen affinity of human maternal and foetal haemoglobin.

PMID- 16991591
TI  - Experiments on the blood supply of nerves.

PMID- 16991592
TI  - The effects of pressure on conduction in peripheral nerve.

PMID- 16991593
TI  - Determination of the oxygen-combining power of blood with the Barcroft
      differential manometer.

PMID- 16991594
TI  - Periodic changes in respiratory depth, produced by changes in the lung.

PMID- 16991595
TI  - The mechanism of the vasomotor reflexes produced by stimulating mammalian sensory
      nerves.

PMID- 16991596
TI  - Capillary permeability in traumatic shock.

PMID- 16991597
TI  - The effect of exercise on chloride excretion in man during water diuresis and
      during tea diuresis.

PMID- 16991598
TI  - Muscular activity and choline esterase.

PMID- 16991599
TI  - The site of action of some drugs causing stimulation of the circular coat of the
      rabbit's intestine.

PMID- 16991600
TI  - The influence of adrenal cortical deficiency on the histamine content of rat
      tissues.

PMID- 16991601
TI  - Rate of regeneration of peripheral nerves in man.

PMID- 16991602
TI  - Reflex vaso-motor responses of the paw of the cat.

PMID- 16991603
TI  - The influence of posture on the pulmonary blood volume and the alveolar gas
      tensions.

PMID- 16991604
TI  - Chronic suprarenal deficiency and its effects on the responses of the isolated
      intestine in the rabbit.

PMID- 16991605
TI  - An effect of barbiturates on serum cholinesterase.

PMID- 16991607
TI  - The antagonism between the posterior pituitary lobe and insulin.

PMID- 16991606
TI  - The effect of barbiturates on the cholinesterase in different tissues.

PMID- 16991608
TI  - The influence of the sympathetic nervous system on capillary permeability in
      traumatic shock.

PMID- 16991609
TI  - The blood volume of normal animals.

PMID- 16991610
TI  - Differentiation in the absorption of olive oil and oleic acid in the rat.

PMID- 16991611
TI  - The microphonic effect of teleost labyrinths and its biological significance.

PMID- 16991612
TI  - Some experiments on the possible relationship between vitamin C and
      calcification.

PMID- 16991613
TI  - Lipolysis and fat absorption.

PMID- 16991614
TI  - The effect of anoxia on the pressure of the cerebrospinal fluid and on the rate
      of absorption of normal saline solution from the subarachnoid space of dogs under
      ether anaesthesia.

PMID- 16991615
TI  - The output of cortical hormone by the mammalian suprarenal.

PMID- 16991616
TI  - Metabolism of phosphate and carbohydrate in extracts of human muscle and brain.

PMID- 16991617
TI  - The alkali in the pancreatic secretion.

PMID- 16991618
TI  - A comparative biological assay of activity in simple solutions of adrenaline.

PMID- 16991619
TI  - Anaphylaxis to serum proteins in the guinea-pig.

PMID- 16991620
TI  - A study of dehydration by means of balance experiments.

PMID- 16991621
TI  - The secretion of urine during dehydration and rehydration.

PMID- 16991622
TI  - The renal function of newborn infants.

PMID- 16991623
TI  - The determination of plasma volume by the Evans blue method: the analysis of
      haemolysed plasma.

PMID- 16991624
TI  - Changes occurring in plasma and serum on storage and their physiological effects.

PMID- 16991625
TI  - Reversibility of carbohydrate and other changes in rats shocked by a clamping
      technique.

PMID- 16991626
TI  - Absorption of serum proteins from the intestine of the sensitized guinea-pig.

PMID- 16991627
TI  - The excretion of diodone by the isolated perfused dog kidney.

PMID- 16991628
TI  - Effect of age upon dark adaptation.

PMID- 16991629
TI  - Stimulus intensity in relation to excitation and pre- and post-excitatory
      inhibition in isolated elements of mammalian retinae.

PMID- 16991630
TI  - The role of the peripheral stump in the control of fibre diameter in regenerating
      nerves.

PMID- 16991631
TI  - The nature of synaptic transmission in a sympathetic ganglion.

PMID- 16991632
TI  - The action of adrenaline on transmission in the superior cervical ganglion.

PMID- 16991633
TI  - The pressor bases of normal urine.

PMID- 16991634
TI  - The action of vitamin d upon the incisor teeth of rats consuming diets with a
      high or low ca:p ratio.

PMID- 16991635
TI  - Action of acetylcholine, atropine and eserine on the central nervous system of
      the decerebrate cat.

PMID- 16991636
TI  - The effect of morphine and hyoscine on dye concentration curves in plasma volume
      determination.

PMID- 16991637
TI  - The behaviour of the cervix uteri in vivo.

PMID- 16991638
TI  - The excretion of histamine in urine.

PMID- 16991639
TI  - Cation antagonism in blood coagulation.

PMID- 16991640
TI  - The isolation and identification of a pressor base from normal urine.

PMID- 16991641
TI  - Further observations on the effects of alloxan on the pancreatic islets.

PMID- 16991643
TI  - Investigations on muscle atrophies arising from disuse and tenotomy.

PMID- 16991642
TI  - Hyperpnoea in man produced by sudden release of occluded blood.

PMID- 16991644
TI  - Absolute muscle force in the ankle flexors of man.

PMID- 16991645
TI  - The acid-labile CO(2) in mammalian muscle and the pH of the muscle fibre.

PMID- 16991646
TI  - The action of adrenaline and of choline-esters on the uterus of the sheep.

PMID- 16991647
TI  - Liberation of histamine during reactive hyperaemia and muscle contraction in man.

PMID- 16991648
TI  - Emulsification of fat in the intestine of the rat and its relationship to
      absorption.

PMID- 16991649
TI  - Observations on some conditions affecting the rate of hormone output by the
      suprarenal cortex.

PMID- 16991650
TI  - The inhibition of histamine release by a pituitary-adrenal mechanism.

PMID- 16991651
TI  - An optical method for recording peripheral blood pressures and pulse rates in
      unanaesthetized and in anaesthetized rabbits.

PMID- 16991652
TI  - The effects of acute haemorrhage on the peripheral blood pressure in
      unanaesthetized and in anaesthetized rabbits.

PMID- 16991653
TI  - Glycogen in adipose tissue.

PMID- 16991654
TI  - Synthesis of acetylcholine by tissue of the central nervous system.

PMID- 16991655
TI  - Excitability changes at the neuro-muscular junction during tetany.

PMID- 16991656
TI  - Effect of the initial level of the blood pressure upon the response of the human
      subject to blood pressure raising reflexes.

PMID- 16991657
TI  - Respiration and cardiac output in the isolated heart-lung-head preparation in the
      rat.

PMID- 16991658
TI  - Facilitation, inhibition and depression at the ;artificial synapse' formed by the
      cut end of a mammalian nerve.

PMID- 16991659
TI  - The mechanism of water diuresis in normal rats and rabbits as analysed by inulin
      and diodone clearances.

PMID- 16991660
TI  - Observations upon thermal burns: the influence of moderate temperature burns upon
      a proteinase of skin.

PMID- 16991661
TI  - The activity of vagal stretch endings during congestion in perfused lungs.

PMID- 16991662
TI  - Diurnal and sampling variations in the determination of haemoglobin.

PMID- 16991664
TI  - The regional distribution of sweating.

PMID- 16991663
TI  - The effect of adrenalectomy on the contractile power of skeletal muscle.

PMID- 16991665
TI  - The digestibility of the phytic acid of oatmeal in adult man.

PMID- 16991666
TI  - Testing diphenylethylamine compounds for analgesic action.

PMID- 16991667
TI  - The behaviour of T. 1824 (Evans's blue) in circulating blood and a modified
      method for the estimation of plasma volume.

PMID- 16991668
TI  - Determination of haemoglobin and methaemoglobin.

PMID- 16991669
TI  - The effect of chronic administration of adrenaline on the suprarenal cortex and
      the comparison of this effect with that of hexoestrol.

PMID- 16991670
TI  - The influence of duration of sensitization of anaphylaxis in the guinea-pig.

PMID- 16991671
TI  - Formation of acetylcholine in cell-free extracts from brain.

PMID- 16991672
TI  - The electric response of the human eye.

PMID- 16991673
TI  - Experiments on the hypothalamic-pituitary control of water excretion in dogs.

PMID- 16991674
TI  - A study of the effects of rapid ;decompression' in certain animals.

PMID- 16991675
TI  - The effect of cutaneous burns on histamine in mice.

PMID- 16991677
TI  - Resting and action potentials in single nerve fibres.

PMID- 16991676
TI  - On the vasodilatation in human skeletal muscle during post-haemorrhagic fainting.

PMID- 16991678
TI  - The excretion of urea, salts and water during periods of hydropaenia in man.

PMID- 16991679
TI  - The action of gonadotrophic hormone and of pituitary corticotrophic hormone on
      the cholesterol content of the adrenals.

PMID- 16991680
TI  - Effect of intensity of illumination on the matching of solutions of
      carboxyhaemoglobin.

PMID- 16991681
TI  - The effect of magnesium and calcium on the physiological properties of certain
      purine derivatives.

PMID- 16991682
TI  - A comparison of the action of vitamin D on the teeth of rachitic rats with that
      of additional calcium or phosphorus added to rachitogenic diets.

PMID- 16991683
TI  - Interaction of drugs and the effect of cooling on the isolated mammalian
      intestine.

PMID- 16991684
TI  - The metabolism of kidney slices from new-born and full-grown rats.

PMID- 16991685
TI  - The effect of introduction of isotonic sodium chloride solution into the cisterna
      magna of the dog on the cell content of the cerebrospinal fluid.

PMID- 16991686
TI  - The accuracy of haemoglobin determination by the copper sulphate-blood gravity
      method in indian soldiers.

PMID- 16991687
TI  - Urine acidity in alcohol diuresis in man.

PMID- 16991688
TI  - The effect of local temperature on fluid loss in thermal burns.

PMID- 16991689
TI  - The normal course of separation of the pubes in pregnant mice.

PMID- 16991690
TI  - The renal action of posterior pituitary extract and its fractions as analysed by
      clearance experiments on rats.

PMID- 16991691
TI  - Factors influencing deposition of glycogen in adipose tissue of the rat.

PMID- 16991692
TI  - Temperature and blood flow in the human forearm.

PMID- 16991693
TI  - The effect of magnesium deficiency on neuro-muscular transmission in the shore
      crab carcinus maenas.

PMID- 16991694
TI  - The normal visual (rod) field of the dark-adapted eye.

PMID- 16991695
TI  - The stimulating action of acetylcholine on the heart.

PMID- 16991696
TI  - Normal variations in blood haemoglobin concentration.

PMID- 16991697
TI  - The effects of adrenaline on blood haemoglobin concentration.

PMID- 16991698
TI  - Properties and distribution of the enzyme system which synthesizes acetylcholine
      in nervous tissue.

PMID- 16991699
TI  - Circulatory changes during fainting and coma caused by oxygen lack.

PMID- 16991700
TI  - The effect of ethyl alcohol and some other diuretics on chloride excretion in
      man.

PMID- 16991701
TI  - The osmotic pressure of human foetal and maternal sera.

PMID- 16991702
TI  - The partition of potassium between the isolated lung of the dog and its perfusate
      with particular reference to the action of adrenaline.

PMID- 16991703
TI  - The effect of dietary restriction upon the incisor teeth of rachitic rats.

PMID- 16991704
TI  - Rod and cone components in the electric response of the eye.

PMID- 16991705
TI  - The presence of a sympathomimetic substance in extracts of mammalian heart.

PMID- 16991706
TI  - The distribution of excitation and inhibition in single-fibre responses from a
      polarized retina.

PMID- 16991707
TI  - An investigation for the presence of a skin protease inhibitory factor in burned
      skin.

PMID- 16991708
TI  - Changes in intestinal tone and motility associated with nausea and vomiting.

PMID- 16991709
TI  - On the occurrence in vitro of cells resembling osteoclasts.

PMID- 16991710
TI  - Observations on plasma volume estimations with the dye T 1824.

PMID- 16991711
TI  - Reflexes elicited by visceral stimulation in the acute spinal animal.

PMID- 16991712
TI  - The site of pressor action of the base a, closely allied to l-nicotine, present
      in urine.

PMID- 16991713
TI  - The appearance of a base, detected by a colour test, in the urine of bitches
      having renal ischaemia.

PMID- 16991714
TI  - The properties and pharmacological action of a base liberated by alkaline
      hydrolysis of normal urine, compared with those of a similar base found free in
      the urine of dogs with renal ischaemia.

PMID- 16991715
TI  - Conduction velocity and myelin thickness in regenerating nerve fibres.

PMID- 16991716
TI  - The production and removal of oedema fluid in the lung after exposure to carbonyl
      chloride (phosgene).

PMID- 16991717
TI  - The absorption of fluids from the lungs.

PMID- 16991718
TI  - The nucleoproteins of the liver cell demonstrated by ultra-violet microscopy.

PMID- 16991720
TI  - Preliminary observations on the narcotic effect of xenon with a review of values
      for solubilities of gases in water and oils.

PMID- 16991721
TI  - The metabolism of kidney slices from new-born and mature animals.

PMID- 16991719
TI  - Hyperpnoea induced by forced breathing.

PMID- 16991722
TI  - Relation between illumination and extent of the visual field.

PMID- 16991723
TI  - Urea excretion by rabbits.

PMID- 16991724
TI  - The effect of adreno-corticotrophic hormone on the respiratory metabolism of the
      adrenal cortex of the rat.

PMID- 16991725
TI  - Maternal and foetal tissue- and plasma-lipids in normal and cholesterol-fed
      rabbits.

PMID- 16991726
TI  - On the action of adrenaline on the blood vessels in human skeletal muscle.

PMID- 16991727
TI  - The experimental production of watery vacuolation of the liver.

PMID- 16991729
TI  - The colour sensitivity of the retina within the central fovea of man.

PMID- 16991728
TI  - The rate and site of acetate metabolism in the body.

PMID- 16991730
TI  - The effect of limb position in seated subjects on their ability to utilize the
      maximum contractile force of the limb muscles.

PMID- 16991731
TI  - The ferricyanide method of blood-gas analysis.

PMID- 16991732
TI  - Experiments on liver sympathin.

PMID- 16991733
TI  - The action of chemical vesicants on cholinesterase.

PMID- 16991734
TI  - Vitamin A and bone growth: the reversibility of vitamin A-deficiency changes.

PMID- 16991735
TI  - The potentiating action of acetylcholine on that of adrenaline.

PMID- 16991736
TI  - The action of soya-bean trypsin inhibitor as an anti-thromboplastin in blood
      coagulation.

PMID- 16991737
TI  - The effect of oestrone and relaxin on the x-ray appearance of the pelvis of the
      mouse.

PMID- 16991738
TI  - Antidiuretic hormone in pituitary glands of new-born rats.

PMID- 16991739
TI  - The effect of severe burns and some protein-precipitants on skin-histamine in
      cats.

PMID- 16991740
TI  - The effects of analeptics on the fatigued subject.

PMID- 16991741
TI  - Binocular summation within the nervous pathways of the pupillary light reflex.

PMID- 16991742
TI  - Subthreshold potentials in medullated nerve.

PMID- 16991743
TI  - The effects of magnesium ions and of creatine phosphate on the synthesis of
      acetylcholine.

PMID- 16991744
TI  - Action of intrathecally injected eserine on the spinal cord of the cat.

PMID- 16991745
TI  - The nervous pathways of intestinal reflexes associated with nausea and vomiting.

PMID- 16991746
TI  - An experimental analysis of the jugular pulse in man.

PMID- 16991747
TI  - The optimum intrapulmonary pressure in underwater respiration.

PMID- 16991748
TI  - The electrical activity of isolated mammalian intestines.

PMID- 16991749
TI  - The distribution of nucleotide, phosphocreatine and glycogen in the heart.

PMID- 16991750
TI  - Studies on the effect of l-tyrosine on the white rat.

PMID- 16991751
TI  - Rigor mortis and adenosine-triphosphate.

PMID- 16991752
TI  - The effect of seat position on the efficiency of bicycle pedalling.

PMID- 16991753
TI  - The effects of changes in dietary protein on the composition and structure of the
      liver cell.

PMID- 16991754
TI  - Effects of intrathecal injection of KCl and other solutions in cats. Excitatory
      action of K ions on posterior nerve root fibres.

PMID- 16991755
TI  - Creatinine losses in the sweat during work in hot humid environments.

PMID- 16991756
TI  - The response of newborn rats to administration of water by the stomach.

PMID- 16991757
TI  - The response of adult and suckling rats to the administration of water and of
      hypertonic solutions of urea and salt.

PMID- 16991758
TI  - The action of acetylcholine in the supraoptic nucleus of the chloralosed dog.

PMID- 16991759
TI  - Reflex vasodilatation in human skeletal muscle in response to heating the body.

PMID- 16991760
TI  - The survival of transplanted embryo bone grafted to chorioallantoic membrane, and
      subsequent osteogenesis.

PMID- 16991761
TI  - The mechanical and structural properties of bone in rats on a rachitogenic diet.

PMID- 16991762
TI  - The normal visual (rod) field of the dark-adapted eye.

PMID- 16991763
TI  - The membrane resistance of a non-medullated nerve fibre.

PMID- 16991764
TI  - The effect of potassium on the surface membrane of an isolated axon.

PMID- 16991765
TI  - Potassium leakage from an active nerve fibre.

PMID- 16991766
TI  - The effect of change of brightness level upon the foveal luminosity curve
      measured with small fields.

PMID- 16991767
TI  - The histaminolytic action of blood during pregnancy.

PMID- 16991768
TI  - Cortical lipids of the normal and denervated suprarenal gland under conditions of
      stress.

PMID- 16991769
TI  - The effect of calcium ions on the respiration of kidney slices of newborn and
      mature rats.

PMID- 16991770
TI  - The effect of electrolyte deficiency on the rate of conduction in a single nerve
      fibre.

PMID- 16991771
TI  - Quantitative studies of adrenaline and noradrenaline.

PMID- 16991772
TI  - The estimation of adrenaline in normal rabbit's blood.

PMID- 16991773
TI  - Inulin, diodone, creatinine and urea clearances in newborn infants.

PMID- 16991774
TI  - The mechanism of the sting of the common nettle (urtica urens).

PMID- 16991775
TI  - Some factors affecting the acidity of urine in man.

PMID- 16991776
TI  - Vagal nerve fibre activity following multiple pulmonary embolism.

PMID- 16991777
TI  - The motility and viability of rabbit spermatozoa at different hydrogen-ion
      concentrations.

PMID- 16991778
TI  - The smooth muscle contracting effects of various substances supposed to act on
      nervous structures in the intestinal wall.

PMID- 16991779
TI  - The threshold of angular acceleration perception.

PMID- 16991780
TI  - The action of phosgene on the stretch receptors of the lung.

PMID- 16991781
TI  - The action of adrenaline on mammalian skeletal muscle.

PMID- 16991783
TI  - A note on the shape of pipettes used in blood gas analysis.

PMID- 16991782
TI  - An automatic method for the collection of the alveolar air.

PMID- 16991784
TI  - The nature of the acclimatization occurring during repeated exposure of the human
      subject to atmospheres containing low concentrations of carbon monoxide.

PMID- 16991785
TI  - The action of tetanus toxin on the rabbit's iris.

PMID- 16991786
TI  - Rods, cones and the localization of pre-excitatory inhibition in the mammalian
      retina.

PMID- 16991787
TI  - Inspiratory vaso-constriction in patients after spinal injuries.

PMID- 16991788
TI  - Vaso-constriction in the finger after deep inspiration.

PMID- 16991789
TI  - Renal excretion of sodium and potassium in rats.

PMID- 16991790
TI  - The effects of pancreozymin and of vagal nerve stimulation upon the histological
      appearance of the pancreas.

PMID- 16991791
TI  - Sensitivity of the small intestine.

PMID- 16991792
TI  - The effect of variations in osmotic pressure and electrolyte concentration on the
      motility of rabbit spermatozoa at different hydrogen-ion concentrations.

PMID- 16991793
TI  - The distribution of reducing substances between the intra-ocular fluids and blood
      plasma, and the kinetics of penetration of various sugars into these fluids.

PMID- 16991794
TI  - The action of carbon dioxide and cyanide on foetal respiratory movements; the
      development of chemoreflex function in sheep.

PMID- 16991795
TI  - An outflow recorder useful for detecting small amounts of vasopressin.

PMID- 16991796
TI  - The local electric changes associated with repetitive action in a non-medullated
      axon.

PMID- 16991797
TI  - Phosphate clearances in infants and adults.

PMID- 16991798
TI  - The directional and spectral sensitivities of the retinal rods to adapting fields
      of different wave-lengths.

PMID- 16991799
TI  - Sulphanilamide inhibition of carbonic anhydrase in whole blood.

PMID- 16991800
TI  - The stimulating action of phosphate compounds on the perfused superior cervical
      ganglion of the cat.

PMID- 16991801
TI  - The secretion of adrenaline from the perfused suprarenal gland.

PMID- 16991802
TI  - Effect of ulnar nerve block on blood flow in the reflexly vasodilated digit.

PMID- 16991803
TI  - Ascorbic acid in adrenal blood.

PMID- 16991804
TI  - The effects of sucrose upon gruel fractional test meals.

PMID- 16991805
TI  - The influence of thyroxine and adrenal cortical extract on the oxygen consumption
      of adrenalectomized rats.

PMID- 16991806
TI  - The influence of ovarian hormones on the transmission of the activity of the
      sympathetic nerves of the cat.

PMID- 16991808
TI  - The mechanism of haemostasis in peripheral vessels.

PMID- 16991807
TI  - The relationship between the change in the electroretinogram and the subjective
      dark-adaptation curve.

PMID- 16991809
TI  - The action of acetylcholine and adrenaline on flexor and extensor movements
      evoked by stimulation of the descending motor tracts.

PMID- 16991810
TI  - The effects of small amounts of carboxyhaemoglobin on the determination of oxygen
      in the blood by the Haldane and van Slyke methods.

PMID- 16991811
TI  - Some effects of nicotine-like substances and their relation to sensory nerve
      endings.

PMID- 16991812
TI  - Some properties of amarin, with special reference to its use in conjunction with
      adrenaline for the production of idio-ventricular rhythms.

PMID- 16991813
TI  - The oxidation of haemoglobin to methaemoglobin by oxygen.

PMID- 16991814
TI  - Observations on the urine, blood and arterial pressure of dogs before and after
      the production of renal ischaemia.

PMID- 16991815
TI  - The effect of diisopropyl fluorophosphonate on neuromuscular transmission in
      cats.

PMID- 16991816
TI  - An integration of the total oxygen consumption of the sheep foetus from that of
      the tissues.

PMID- 16991817
TI  - The presence of a peptic synergist in gastric juice: its importance in the
      estimation of the proteolytic activity of gastric juice.

PMID- 16991818
TI  - Acetylcholine synthesis in different regions of the central nervous system.

PMID- 16991820
TI  - The relative humidity of the skin.

PMID- 16991819
TI  - The assay of the nutritive value of a protein by its effect on liver cytoplasm.

PMID- 16991821
TI  - Stimulation of the supraopticohypophysial tract in the conscious rabbit with
      currents of different wave form.

PMID- 16991822
TI  - Electrical stimulation of the hypothalamus and the mechanism of neural control of
      the adenohypophysis.

PMID- 16991823
TI  - The excretion of an antidiuretic substance by the kidney, after electrical
      stimulation of the neurohypophysis in the unanaesthetized rabbit.

PMID- 16991824
TI  - Further evidence regarding the endocrine status of the neurohypophysis.

PMID- 16991825
TI  - The standardization of secretin and pancreozymin.

PMID- 16991826
TI  - The sounds from single motor units in a contracting muscle.

PMID- 16991827
TI  - The measurement of chloride losses in the sweat.

PMID- 16991829
TI  - Oxygen tension and the respiration of resting frog's muscle.

PMID- 16991828
TI  - The activity of the duodenum.

PMID- 16991830
TI  - Afferent nerve fibres from the heart and lungs in the cervical vagus.

PMID- 16991831
TI  - Osteogenesis around multiple fragments of chick embryo bone grafted to developing
      chick embryo chorioallantois.

PMID- 16991832
TI  - The pressure developed in muscle during contraction.

PMID- 16991843
TI  - Fructose in the sheep foetus.

PMID- 16991844
TI  - The peripheral action of Cl. botulinum toxin.

PMID- 16991845
TI  - The determination of the blood volume in man by the carbon monoxide and dye
      methods.

PMID- 16991846
TI  - A foetal plethysmograph.

PMID- 16991847
TI  - The umbilical blood flow in the foetal sheep.

PMID- 16991849
TI  - The passage into the embryonic yolk-sac cavity of maternal plasma proteins in
      rabbits.

PMID- 16991848
TI  - A method for measuring the blood flow in the umbilical vessels.

PMID- 16991850
TI  - Bradycardia of central origin produced by injections of tetanus toxin into the
      vagus nerve.

PMID- 16991851
TI  - Effect of the protein content of the diet on the glomerular filtration rate of
      young and adult rats.

PMID- 16991852
TI  - The penetration of some electrolytes and non-electrolytes into the aqueous humour
      and vitreous body of the cat.

PMID- 16991853
TI  - Action of adrenaline-like substances on the serum potassium.

PMID- 16991854
TI  - The excitation and contraction of the flight muscles of insects.

PMID- 16991856
TI  - Cation control in human erythrocytes.

PMID- 16991855
TI  - The effect of protein hydrolysates (leukotaxine) on skin-histamine in cats.

PMID- 16991857
TI  - The effect of breathing oxygen at atmospheric pressure on tissue oxygen and
      carbon dioxide tensions.

PMID- 16991858
TI  - Activity and drug responses of the sheep uterus in relation to reproductive
      condition.

PMID- 16991859
TI  - Opacity changes in stimulated nerve.

PMID- 16991860
TI  - Observations on the action of prostigmine on the spinal cord of the cat.

PMID- 16991861
TI  - Changes in transparency of muscle during a twitch.

PMID- 16991862
TI  - Effects of dehydration on adult and newborn rats.

PMID- 16991863
TI  - Evidence for saltatory conduction in peripheral myelinated nerve fibres.

PMID- 16991864
TI  - The effect of postural and exercise components on the heart rate during a brief
      step test.

PMID- 16991865
TI  - The effect of the posterior pituitary hormones on the inorganic phosphorus and
      sugar of the blood.

PMID- 16991866
TI  - The metabolic cost of passive cycling movements.

PMID- 16991867
TI  - Observation of the hypophysioportal vessels of the living rat.

PMID- 16991868
TI  - The causes of serum bradycardia.

PMID- 16991869
TI  - The influence of magnesium on respiration, glycolysis and cholinesterase activity
      in rat brain.

PMID- 16991870
TI  - Action of condensed alkyl phosphates on the nerve-muscle preparation and the
      central nervous system of the cat.

PMID- 16991871
TI  - Method for the frequent estimation of forearm blood flow under conditions of
      decreased atmospheric pressure.

PMID- 16991872
TI  - The determination of blood volume by the carbon monoxide and dye (T-1824) methods
      in rabbits.

PMID- 16991873
TI  - Effect of nembutal anaesthesia on restoration of plasma volume after haemorrhage
      in dogs, cats and rabbits.

PMID- 16991874
TI  - Enzymic formation of pressor amines.

PMID- 16991875
TI  - The changes in water and chloride distribution during heavy sweating.

PMID- 16991876
TI  - The effect of the application of an arterial occlusion cuff to the wrist on the
      blood flow in the human forearm.

PMID- 16991877
TI  - The timing of certain circulatory events in man.

PMID- 16991878
TI  - The estimation of adrenaline and allied substances in blood.

PMID- 16991879
TI  - The effect of nicotine on the diuresis induced by ethyl alcohol.

PMID- 16991880
TI  - The nature of splenic sympathin.

PMID- 16991881
TI  - The dependence of neuromuscular transmission on glucose.

PMID- 16991882
TI  - Action of acetylcholine on rabbit auricles in relation to acetylcholine
      synthesis.

PMID- 16991883
TI  - Noradrenaline in tumours of the adrenal medulla.

PMID- 16991884
TI  - On the Relation between the Structure, Function, Distribution and Origin of the
      Cranial Nerves; together with a Theory of the Origin of the Nervous System of
      Vertebrata.

PMID- 16991885
TI  - Proceedings of the Physiological Society, 1889. No. II.

PMID- 16991886
TI  - Observations on Human Bile obtained from a case of Biliary Fistula.

PMID- 16991887
TI  - Cerebro-Spinal Fluid.

PMID- 16991888
TI  - On the Electrical Organ of the Skate: Part II.

PMID- 16991889
TI  - On the Regulation of Respiration: Part II. Theoretical.

PMID- 16991890
TI  - On the Physiology of the Salivary Secretion: Part V. The effect of stimulating
      the cerebral secretory nerves upon the amount of saliva obtained by stimulating
      the sympathetic nerve.

PMID- 16991891
TI  - The Coagulation Question.

PMID- 16991892
TI  - Further Observations on the Histology and Function of the Mammalian Sympathetic
      Ganglia.

PMID- 16991893
TI  - The Innervation of the Renal Blood Vessels.

PMID- 16991894
TI  - On the Structure of the Vertebrate Liver.

PMID- 16991896
TI  - Proceedings of the Physiological Society, 1889. No. IV.

PMID- 16991895
TI  - On Nerve-Tracts degenerating secondarily to Lesions of the Cortex Cerebri.

PMID- 16991897
TI  - Proceedings of the Physiological Society, 1889. No. III.

PMID- 16991898
TI  - On the Histology of the Mucous Salivary Glands, and on the Behaviour of their
      Mucous Constituents.

PMID- 16991899
TI  - On the Stimulation Effects in a Polarised Nerve during and after the flow of the
      Polarising Current.

PMID- 16991900
TI  - The Stromata of the Red Corpuscles.

PMID- 16991902
TI  - On the Reglation of Respiration: PART I. Experimental.

PMID- 16991901
TI  - On Formation of Scar-tissue.

PMID- 16991903
TI  - On the Nature of the Knee-Jerk.

PMID- 16991904
TI  - On the Origin of Urohaematoporphyrin and of Normal and Pathological Urobilin in
      the Organism.

PMID- 16991905
TI  - Proceedings of the Physiological Society, 1889. No. I.

PMID- 16991906
TI  - The responses of the blood vessels of the muscles with special reference to their
      central control.

PMID- 16991907
TI  - Some factors influencing the passage of fluid through intestinal loops in dogs.

PMID- 16991908
TI  - The inorganic components of gastric secretion.

PMID- 16991909
TI  - The accuracy of the Meyerstein haematocrit.

PMID- 16991910
TI  - An analysis of the response from single visual-purple-dependent elements, in the
      retina of the cat.

PMID- 16991911
TI  - The response of the rabbit's endometrium to uterine implants of progesterone and
      other steroids.

PMID- 16991912
TI  - The effects of adrenaline and of sympathetic stimulation on the demarcation
      potential of mammalian skeletal muscle.

PMID- 16991913
TI  - The responses of the heart rate and the systolic blood pressure to a series of
      sympathomimetic amines in the unanaesthetized, atropinized bitch.

PMID- 16991915
TI  - The end-plate potentials of the rat diaphragm preparation.

PMID- 16991914
TI  - Sensitization of sensory receptors in the frog's skin.

PMID- 16991916
TI  - Some properties of the cat's isolated cerebral cortex.

PMID- 16991917
TI  - Interaction between lights of different wave-length in the central fovea.

PMID- 16991918
TI  - The immediate and delayed effects of diisopropylfluorophosphate injected into the
      supraoptic nuclei of dogs.

PMID- 16991919
TI  - Some observations with the phase-contrast microscope upon incinerated human blood
      cells.

PMID- 16991920
TI  - Synthesis of acetylcholine in the wall of the digestive tract.

PMID- 16991921
TI  - Early tension relaxation during a muscle twitch.

PMID- 16991922
TI  - On the Relations of Diaphragmatic and Costal Respiration, with particular
      reference to Phonation.

PMID- 16991923
TI  - Plethysmographic Studies of the Human Vaso-motor Mechanism when excited by
      Electrical Stimulation.

PMID- 16991924
TI  - On the Conditions of Temperature in Nerves (I) during Activity, (II) during the
      Process of Dying.

PMID- 16991925
TI  - A Comparative Study of Artificial and Natural Digestions.

PMID- 16991926
TI  - PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY, 1890. No. I.

PMID- 16991927
TI  - The Crystallization of Haemoglobin in Man and the Lower Animals, and of
      Haemochromogen in Man.

PMID- 16991928
TI  - On the Primary Cleavage Products formed in the Digestion of Gluten-casein of
      Wheat by Pepsin-hydrochloric Acid.

PMID- 16991929
TI  - Crystalline Globulin and Globuloses, or Vitelloses.

PMID- 16991930
TI  - The Proteids of Milk.

PMID- 16991932
TI  - On Muscular Tremor.

PMID- 16991931
TI  - Regarding the Action of Lime Salts on Caseine and on Milk.

PMID- 16991933
TI  - The Cause of the First Sound of the Heart.

PMID- 16991934
TI  - Remarks on the Chemistry of Respiration in the Horse during rest and work.

PMID- 16991935
TI  - Note on the Composition of the Sweat of the Horse.

PMID- 16991937
TI  - Proceedings of the Physiological Society, 1890. No. IV.

PMID- 16991936
TI  - Note on the Time Relations of Stimulation of the Optic Lobes of the Frog.

PMID- 16991939
TI  - Observations on the Composition and Flow of Chyle from the Thoracic Duct in Man.

PMID- 16991938
TI  - The Effect upon the Bodily Temperature of Lesions of the Corpus Striatum and
      Optic Thalamus.

PMID- 16991940
TI  - A Method of raising the Specific Gravity of the Blood.

PMID- 16991941
TI  - On the Physiology of the Salivary Secretion: Part VI. Chiefly upon the
      connections of peripheral nerve cells with the nerve fibres which run to the sub
      lingual and sub-maxillary glands.

PMID- 16991942
TI  - The Knee-jerk and its Physiological Modifications.

PMID- 16991943
TI  - The Chemistry of Respiration in the Horse during Rest and Work.

PMID- 16991944
TI  - Concerning Experiments to test the Influence of Lime, Sodium and Potassium Salts
      on the Development of Ova and Growth of Tadpoles.

PMID- 16991945
TI  - On the Regulation of the Blood-supply of the Brain.

PMID- 16991946
TI  - PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY, 1889. No. V.

PMID- 16991948
TI  - Notes on the mode of action of Rennin and Fibrin-ferment.

PMID- 16991947
TI  - Pituri and Nicotin.

PMID- 16991949
TI  - Osmosis Experiments with Living and Dead Membranes.

PMID- 16991950
TI  - Voluntary and Reflex Muscular Contraction.

PMID- 16991951
TI  - The Influence of certain Salts upon the act of Clotting.

PMID- 16991952
TI  - On the Physiological Mechanism of the Phenomenon termed "Tendon Reflex".

PMID- 16991953
TI  - Remarks on the Chemistry of respiration in the Horse during Rest and Work.

PMID- 16991954
TI  - Further Note on Degenerations following Lesions of the Cerebral Cortex.

PMID- 16991956
TI  - Proceedings of the Physiological Society, 1890. No. III.

PMID- 16991955
TI  - Proceedings of the Physiological Society, 1890. No. II.

PMID- 16991957
TI  - The Action of Alcohols and Aldehydes on Proteid Substances.

PMID- 16991959
TI  - The Primary Cleavage Products formed in the Digestion of Gelatin.

PMID- 16991958
TI  - The Relative Formation of Proteoses and Peptones in Gastric Digestion.

PMID- 16991960
TI  - Myosin-Peptone.

PMID- 16991962
TI  - Physiology of the communicating branch between the Superior and the Inferior
      Laryngeal Nerves.

PMID- 16991961
TI  - On the Composition and Action of Peptonised Milk.

PMID- 16991963
TI  - The Influence of Bile on the Fatsplitting Properties of Pancreatic Juice.

PMID- 16991965
TI  - Proceedings of the Physiological Society, 1890. No. VI.

PMID- 16991964
TI  - The Proteids in Milk.

PMID- 16991966
TI  - On some Improvements in the Method of graphically recording the Variations in the
      Level of a Surface of Mercury, e.g. in the Kymograph of Ludwig.

PMID- 16991967
TI  - The Interference Kymoscope, an Apparatus for demonstrating many of the Phenomena
      of Wave Motion.

PMID- 16991968
TI  - The Circulation Kymoscope, an arrangement for demonstrating many of the Physical
      Phenomena of the Circulation.

PMID- 16991969
TI  - Further Observations on the Behaviour of Caseinogen.

PMID- 16991970
TI  - The Action of Salts upon Heat Coagulation.

PMID- 16991971
TI  - On the Conditions which determine the Distribution of the Coagulation following
      the Intra-vascular Injection of a Solution of Wooldridge's Tissue Fibrinogen:
      Preliminary Communication.

PMID- 16991972
TI  - Senescence and Rejuvenation.

PMID- 16991973
TI  - Proceedings of the Physiological Society, 1891. No. I.

PMID- 16991974
TI  - Proceedings of the Physiological Society, 1891. No. II.

PMID- 16991975
TI  - The changes produced in Casein by the action of Pancreatic and Rennet Extracts.

PMID- 16991976
TI  - The influence of Alcohol on Proteid Metabolism.

PMID- 16991978
TI  - On the relation of the temperature of the Groin to that of the Rectum in the
      Rabbit, both normally and after destruction of the Cerebral Cortex.

PMID- 16991977
TI  - On the position and value of those Lesions of the Brain which cause a rise of
      Temperature.

PMID- 16991979
TI  - On Pilomotor Nerves.

PMID- 16991981
TI  - Proceedings of the Physiological Society, 1891. No. III.

PMID- 16991980
TI  - Note on Cheyne-Stokes Breathing in the Frog.

PMID- 16991982
TI  - Proceedings of the Physiological Society, 1891. No. IV.

PMID- 16991983
TI  - Further Observations on the Specific Gravity of the Blood in Health and Disease.

PMID- 16991984
TI  - On the Course and Connections of the Secretory Fibres supplying the Sweat Glands
      of the Feet of the Cat.

PMID- 16991985
TI  - Note on the Connection with Nerve-cells of the Vaso-motor Nerves for the Feet.

PMID- 16991986
TI  - The influence of Calcium Chloride on Egg Albumen and some of its derivatives.

PMID- 16991987
TI  - Proceedings of the Physiological Society, 1891. No. V.

PMID- 16991988
TI  - The behaviour of Saccharine Matter in the Blood.

PMID- 16991989
TI  - Notes on some Applications in Physiology of the "Resistance" Method of measuring
      Temperature, with special reference to the question of Heat Production in
      Mammalian Nerves during Excitation.

PMID- 16991990
TI  - The Cardiopneumatic Movements.

PMID- 16991991
TI  - The Movements of the Heart within the Chest Cavity and the Cardiogram.

PMID- 16991992
TI  - On the Excretion of Uric Acid and Urea.

PMID- 16991993
TI  - On the Excretion of Uric Acid, Urea and Ammonia, with a Scheme of Curves.

PMID- 16991994
TI  - On the Estimation of Uric Acid in Human Urine.

PMID- 16991996
TI  - A Physiological, Histological and Clinical Study of the Degeneration and
      Regeneration in Peripheral Nerve Fibres after Severance of their connections with
      the Nerve Centres.

PMID- 16991995
TI  - The function of receptors in the statocyst of the lobster Homarus americanus.

PMID- 16991997
TI  - On some Points in the Innervation of the Mammalian Heart.

PMID- 16991998
TI  - A new form of Apparatus for measuring the Respiratory Exchange of Animals.

PMID- 16991999
TI  - On the Method of transmission of the impulse in Medullated Fibres.

PMID- 16992000
TI  - The absorption of Water in the Alimentary Canal.

PMID- 16992001
TI  - The action of Nicotin on the Ciliary Ganglion and on the endings of the Third
      Cranial Nerve.

PMID- 16992002
TI  - Proceedings of the Physiological Society, 1892. No. III.

PMID- 16992003
TI  - Proceedings of the Physiological Society, 1892. No. IV.

PMID- 16992004
TI  - Ferment Actions of the Pancreas in different animals.

PMID- 16992005
TI  - On Fractional Heat-Coagulation.

PMID- 16992006
TI  - Researches on the Filling of the Heart.

PMID- 16992008
TI  - On the Occurrence and Detection of Haematoporphyrin in the Urine.

PMID- 16992007
TI  - On the Mechanism of the Movements of the Iris.

PMID- 16992009
TI  - Notes on the Arrangement of some Motor Fibres in the Lumbo-Sacral Plexus.

PMID- 16992010
TI  - Proceedings of the Physiological Society, 1892. No. V.

PMID- 16992011
TI  - Some of the Influences which affect the power of Voluntary Muscular Contractions.

PMID- 16992012
TI  - The Blood-corpuscles of the Crustacea, together with a suggestion as to the
      Origin of the Crustacean Fibrin-ferment: PART I.

PMID- 16992014
TI  - Proceedings of the Physiological Society, 1891. No. VI.

PMID- 16992013
TI  - The Influence of Temperature and of Endocardiac Pressure on the Heart, and
      perticularly on the Action of the Vagus and Cardiac Sympathetic Nerves.

PMID- 16992015
TI  - A Contribution to our knowledge of Taste Sensations.

PMID- 16992016
TI  - On the Respiratory Changes of the Intrathoracic Pressure, measured in the
      Mediastinum Posterior.

PMID- 16992017
TI  - On Retractile Cilia in the Intestine of Lumbricus Terrestris.

PMID- 16992019
TI  - The Nature of Cobra Poison.

PMID- 16992018
TI  - On a Large-fibred Sensory Supply of the Thoracic and Abdominal Viscera.

PMID- 16992020
TI  - Further Observation on the Influence of Calcium Salts in promoting Heat
      Coagulation of Albumins.

PMID- 16992021
TI  - The Protective Functions of the Skin of certain Animals.

PMID- 16992022
TI  - On the Excretion of Uric Acid, and its Estimation by Haycraft's Process. A Reply.

PMID- 16992024
TI  - Proceedings of the Physiological Society, 1892. No. I.

PMID- 16992023
TI  - The Fibres of Retiform Tissue.

PMID- 16992025
TI  - Proceedings of the Physiological Society, 1892. No. II.

PMID- 16992026
TI  - Excitability changes in afferent fibre terminations and their relation to slow
      potentials.

PMID- 16992027
TI  - Temporary nutritional stress and infertility in female mice.

PMID- 16992028
TI  - The dependence of tension upon extension in the stretch reflex of the soleus
      muscle of the decerebrate cat.

PMID- 16992029
TI  - A study of certain factors influencing the stretch reflex of the decerebrate cat.

PMID- 16992030
TI  - Release of gastrin from the pyloric antrum following vagal stimulation by sham
      feeding in dogs.

PMID- 16992031
TI  - Neurohormones of the pericardial organs of brachyuran Crustacea.

PMID- 16992032
TI  - A Physiological, Histological, and Clinical Study of the Degeneration and
      Regeneration in Peripheral Nerve Fibres after severance of their connections with
      the Nerve Centres: Part III. Critical Resume of Surgical cases of Primary and
      Secondary Suture.

PMID- 16992033
TI  - The Influence of Carbonic Acid dissolved in saline solutions on the Ventricle of
      the Frog's Heart.

PMID- 16992034
TI  - Variations experimentally produced in the Specific Gravity of the Blood.

PMID- 16992035
TI  - Alterations in the strength which occur during fatiguing Voluntary Muscular Work.

PMID- 16992036
TI  - Proceedings of the Physiological Society, 1892. No. VI.

PMID- 16992037
TI  - On certain Proteid and Albuminoid Reactions and their significance.

PMID- 16992038
TI  - Observations on the Physiology of the Embryonic Heart.

PMID- 16992039
TI  - On the Nervous Supply of the Dog's Heart.

PMID- 16992040
TI  - A Comparison of Artificial and Natural Gastric Digestion, together with a Study
      of the Diffusibility of Proteoses and Peptone.

PMID- 16992042
TI  - On the Muscle-nerve Physiology of the Crayfish especially with regard to
      Inhibition.

PMID- 16992041
TI  - The Action of the Epiglottis during Deglutition.

PMID- 16992043
TI  - Action of the Inorganic Salts of Serum, Milk, Gastric Juice, etc., upon the
      isolated working Heart, with remarks upon the causation of the Heart-beat.

PMID- 16992044
TI  - On the Chemical Stimulation of Nerves.

PMID- 16992045
TI  - Proceedings of the Physiological Society, 1893. No. I.

PMID- 16992047
TI  - Proceedings of the Physiological Society, 1892. No. VII.

PMID- 16992046
TI  - Contributions to the Physiology of Lymph Secretion.

PMID- 16992048
TI  - Note on the Spinal portion of some Ascending Degenerations.

PMID- 16992049
TI  - On the Physiology of the Depressor Nerve.

PMID- 16992050
TI  - Urobilin and Allied Pigments.

PMID- 16992051
TI  - Mucin Granules of Myxine.

PMID- 16992052
TI  - Researches on the Structure and Function of the Mammalian Heart.

PMID- 16992053
TI  - Proceedings of the Physiological Society, 1893. No. II.

PMID- 16992054
TI  - Proceedings of the Physiological Society, 1893. No. III.

PMID- 16992055
TI  - The fractionation and purification of factor I.

PMID- 16992056
TI  - Effects of pregnancy on inulin and para-aminohippurate clearances in the
      anaesthetized rat.

PMID- 16992057
TI  - The function of the metanephros of foetal rabbits and pigs.

PMID- 16992058
TI  - The acid-base relationships of the foetal fluids of the pig.

PMID- 16992059
TI  - The uptake of I by the hair of the rat.

PMID- 16992060
TI  - Vasomotor fibres to skin in the upper arm, calf and thigh.

PMID- 16992061
TI  - Tissue 5-hydroxytryptamine and urinary 5-hydroxyindoleacetic acid after partial
      or total removal of the gastro-intestinal tract in the rat.

PMID- 16992062
TI  - On the excitant effect of acetylcholine on structures in the preganglionic trunk
      of the cervical sympathetic: with a note on the anatomical complexities of the
      region.

PMID- 16992063
TI  - The survival of young rats in nitrogen.

PMID- 16992064
TI  - Blood sugars and tissue carbohydrate in foetal and infant lambs and rhesus
      monkeys.

PMID- 16992065
TI  - Observations on the leptomeningeal collateral circulation in dogs.

PMID- 16992066
TI  - The effect of initial strip length on the noradrenaline-induced contraction of
      arterial strips.

PMID- 16992067
TI  - The osmotic effects of some simple molecules and ions on gastric emptying.

PMID- 16992068
TI  - Recurrent inhibition in relation to frequency of firing and limitation of
      discharge rate of extensor motoneurones.

PMID- 16992069
TI  - The sodium-potassium hypothesis as the basis of electrical activity in frog
      ventricle.

PMID- 16992071
TI  - Enzymic oxidation of 5-hydroxytryptamine by pig serum.

PMID- 16992070
TI  - Synaptic potentials, after-potentials, and slow rhythms of lateral geniculate
      neurones.

PMID- 16992072
TI  - The electromagnetic measurement of the flow of digesta through the duodenum of
      the goat and the sheep.

PMID- 16992073
TI  - Frog's spinal cord potentials generated by stimulation of cutaneous nerves.

PMID- 16992074
TI  - Accommodation in motoneurones of the rat and the cat.

PMID- 16992075
TI  - The static elastic properties of the arterial wall.

PMID- 16992076
TI  - The dynamic elastic properties of the arterial wall.

PMID- 16992077
TI  - The distribution and metabolism of thyroxine and 3:5:3'-triiodothyronine in the
      rabbit.

PMID- 16992078
TI  - Acetylcholine and the sympathetic innervation of the spleen.

PMID- 16992079
TI  - Acute insulin deficiency provoked in the dog, pig and sheep by single injections
      of anti-insulin serum.

PMID- 16992080
TI  - Renal transtubular flux of electrolytes in dogs with special reference to
      calcium.

PMID- 16992081
TI  - Rubidium and caesium entry, and cation interaction in frog skeletal muscle.

PMID- 16992082
TI  - The effect of altering the skin temperature of the legs on the forearm sweat
      rate.

PMID- 16992083
TI  - The action of 5-hydroxytryptamine and related compounds on neuromuscular
      transmission in the locust Schistocerca gregaria.

PMID- 16992084
TI  - The effect of cyclical heating of the front of the trunk on the forearm sweat
      rate.

PMID- 16992085
TI  - Unit responses from brain-stem nuclei in the pigeon.

PMID- 16992086
TI  - The effect of some catecholamines upon a monosynaptic reflex pathway in the
      spinal cord.

PMID- 16992088
TI  - On the Results of Ligation of the Coronary Arteries.

PMID- 16992087
TI  - Studies of leptomeningeal collateral circulation in Macacus rhesus.

PMID- 16992089
TI  - Influence of Sugar in the Circulation on the Respiratory Gases and Animal Heat.

PMID- 16992091
TI  - Does Uric Acid taken by mouth increase the Excretion of that substance in the
      Urine?

PMID- 16992090
TI  - Note on the Nature of the Dandruff and its Pigment from the Skin of the Horse.

PMID- 16992092
TI  - The Arrangement of the Sympathetic Nervous System, based chiefly on Observations
      upon Pilo-motor Nerves.

PMID- 16992093
TI  - The Physiological Action of Quinoline, Isoquinoline and some of their
      Derivatives.

PMID- 16992094
TI  - Proceedings of the Physiological Society, 1893. No. IV.

PMID- 16992095
TI  - Proceedings of the Physiological Society, 1893. No. V.

PMID- 16992096
TI  - On the Proteolytic Action of Bromelin, the Ferment of Pineapple Juice.

PMID- 16992097
TI  - A Study of the Sense of Equilibrium in Fishes: I.

PMID- 16992098
TI  - Note upon one or two points in the Comparative Histology of the Pancreas.

PMID- 16992100
TI  - Does the non-coagulable Blood obtained by Injections of Wooldridge's Tissue
      Fibrinogen (Nucleoalbumens) contain Peptone or Albumoses?

PMID- 16992099
TI  - On the Changes in the Number and Character of the Wandering Cells of the Frog
      induced by the presence of Urari or of Bacillus Anthracis.

PMID- 16992101
TI  - On some effects upon the Blood produced by the Injection of the Venom of the
      Australian Black Snake (Pseudechis Porphyriacus).

PMID- 16992102
TI  - On the Reaction-Time of Mammals to Changes in the Temperature of their
      surroundings.

PMID- 16992103
TI  - On the Transformation of Maltose to Dextrose.

PMID- 16992104
TI  - The Nature of the Work of the Kidney as shown by the Influence of Atropine and
      Morphine upon the Secretion of Urine: First Communication.

PMID- 16992105
TI  - On the Influence of Bleeding and Transfusion upon the Respiratory exchange.

PMID- 16992106
TI  - The Sensory Motor Functions of the Central Convolutions of the Cerebral Cortex.

PMID- 16992108
TI  - The Influence of Section of the Vagus Nerve on the Disengagement of Gases in the
      Air-bladder of Fishes.

PMID- 16992107
TI  - Chemical Note on the Secretion of Myxine Glutinosa.

PMID- 16992109
TI  - A Study of the Primary Products resulting from the action of Superheated Water on
      coagulated Egg-Albumin.

PMID- 16992110
TI  - Proceedings of the Physiological Society, 1893. No. VI.

PMID- 16992111
TI  - Proceedings of the Physiological Society, 1893. No. VII.

PMID- 16992112
TI  - Researches on the Circulation Time in Organs and on the Influences which affect
      it: Parts I.-III.

PMID- 16992113
TI  - Some further Observations on Urinary Haematoporphyrin.

PMID- 16992114
TI  - The Action of Sodium Oxalate on Voluntary Muscle: Preliminary Communication.

PMID- 16992115
TI  - The Proteids of Nervous Tissues.

PMID- 16992116
TI  - Depolarization of central terminals of Group I afferent fibres from muscle.

PMID- 16992117
TI  - Sustained dilatation in human muscle blood vessels under the influence of
      adrenaline.

PMID- 16992118
TI  - Acceleration of the absorption of unchanged globulin in the new-born calf by
      factors in colostrum.

PMID- 16992119
TI  - Antifibrillatory action.

PMID- 16992120
TI  - A simple method for production of trackless focal lesions with focused
      ultrasound: statistical evaluation of the effects of irradiation on the central
      nervous system of the cat.

PMID- 16992121
TI  - The mechanism of adrenaline-induced inhibition of sympathetic preganglionic
      activity.

PMID- 16992122
TI  - Cation exchanges of lactose-treated human red cells.

PMID- 16992123
TI  - Cortical projection of impulses in the interosseous nerve of the cat's hind limb.

PMID- 16992124
TI  - The potassium and chloride conductance of frog muscle membrane.

PMID- 16992125
TI  - Acetylcholine content of the rabbit plantaris muscle after denervation.

PMID- 16992126
TI  - Choline acetylase in the placenta of man and other species.

PMID- 16992127
TI  - The effect of urinary output upon the excretion of ;ammonia' in man.

PMID- 16992128
TI  - Further investigations on the influence of motoneurones on the speed of muscle
      contraction.

PMID- 16992129
TI  - Somatic nerve pathways through some thoracic rami communicantes.

PMID- 16992130
TI  - Observations on the size of the fluid compartments of rat liver slices in vitro.

PMID- 16992131
TI  - The effects of temperature on the membrane potentials in isolated atria of the
      ground squirrel, Citellus tridecemlineatus.

PMID- 16992132
TI  - The transmission of information in primary receptor neurones and second-order
      neurones of a phasic system.

PMID- 16992133
TI  - The spontaneous release of acetylcholine from the denervated hemidiaphragm of the
      rat.

PMID- 16992134
TI  - On the permeability of mammalian non-myelinated fibres to sodium and to lithium
      ions.

PMID- 16992135
TI  - The ionic requirements for the action of acetylcholine on mammalian non
      myelinated fibres.

PMID- 16992136
TI  - Release of histamine from spleen by kidney extract, reserpine and compound 48/80.

PMID- 16992137
TI  - The spontaneous and evoked release of acetylcholine from the cerebral cortex.

PMID- 16992138
TI  - Milk iron and its metabolism in the lactating rat.

PMID- 16992139
TI  - Alterations in activity of gamma efferents during distension of the bladder in
      the cat.

PMID- 16992140
TI  - Orthodromic activation of single ganglion cells.

PMID- 16992141
TI  - Patterns of innervation of kitten motoneurones.

PMID- 16992142
TI  - Presynaptic inhibition of the monosynaptic reflex pathway in kittens.

PMID- 16992143
TI  - Twenty-four hour rhythm in the mitotic activity of normal mammary epithelium on
      normal and inverted lighting regimens.

PMID- 16992144
TI  - The influence of calcium on the secretory response of the submaxillary gland to
      acetylcholine or to noradrenaline.

PMID- 16992145
TI  - Histidine decarboxylase in the new-born human infant.

PMID- 16992147
TI  - The transplacental passage of fructose, urea and mesoinositol in the direction
      from foetus to mother, as demonstrated by perfusion studies in the sheep.

PMID- 16992146
TI  - Pharmacological properties of acetylcholine-sensitive cells in the cerebral
      cortex.

PMID- 16992148
TI  - Responses of the rat dorsal column system to mechanical stimulation of the hind
      paw.

PMID- 16992149
TI  - Observations on intrinsic kinin-forming factors in human plasma: the effect of
      acid, acetone, chloroform, heat and euglobulin separation on kinin formation.

PMID- 16992150
TI  - Kinin formation and fibrinolysis in human plasma.

PMID- 16992151
TI  - The estimation of vasopressin in the blood and urine of hydrated and dehydrated
      subjects.

PMID- 16992152
TI  - The mechanism of catecholamine release from the adrenal medulla and the role of
      calcium in stimulus-secretion coupling.

PMID- 16992153
TI  - Spontaneous miniature potentials from insect muscle fibres.

PMID- 16992154
TI  - The relation of frequency of detection to intensity of stimulus for a system of
      many independent detectors each of which is stimulated by a m-quantum
      coincidence.

PMID- 16992155
TI  - The Action of Potassium, Sodium and Calcium Salts on Tubifex Rivulorum.

PMID- 16992156
TI  - The Innervation of the Vessels of the Limbs.

PMID- 16992157
TI  - An improved from of Animal Calorimeter.

PMID- 16992158
TI  - On Absorption from and Secretion into the Serous Cavities.

PMID- 16992159
TI  - Note on the Degeneration of the Roots of the Vth Nerve.

PMID- 16992160
TI  - The Proteids of the Thyroid and the Spleen.

PMID- 16992161
TI  - The Pulmonary Circulation.

PMID- 16992162
TI  - The value of Sugar and the effect of Smoking on Muscular Work.

PMID- 16992163
TI  - Observations on Venous Pressures and their Relationship to Capillary Pressures.

PMID- 16992164
TI  - Further Observations on the Electromotive Properties of the Skin of the Common
      Eel.

PMID- 16992165
TI  - The Influence of Mechanical Factors on Lymph Production.

PMID- 16992166
TI  - On the Absorption of Iron in the Animal Body.

PMID- 16992168
TI  - Proceedings of the Physiological Society, March 10, 1894. No. I.

PMID- 16992167
TI  - The Effect of Stimulation and of Changes in Temperature upon the Irritability and
      Conductivity of Nerve-fibres.

PMID- 16992169
TI  - On D'Arsonval's Physical Theory of the Negative Variation.

PMID- 16992171
TI  - On the Formation of Heat in the Salivary Glands.

PMID- 16992170
TI  - The Ground Substance of Connective Tissue.

PMID- 16992172
TI  - Electromotive Phenomena in Non-secretory Epithelia.

PMID- 16992173
TI  - Note on the Degenerations following Double Transverse, Longitudinal, and Anterior
      Cornual Lesions of the Spinal Cord.

PMID- 16992174
TI  - On some Effects of Thyroidectomy in Animals.

PMID- 16992175
TI  - On Reflex Action from Sympathetic Ganglia.

PMID- 16992176
TI  - On the Role of Acid in Protozoan Digestion.

PMID- 16992177
TI  - On red Blood-Corpuscles of Different Specific Oxygen Capacities.

PMID- 16992178
TI  - The Action of Oxalate Solutions on Nerve and Muscle Irritability and Rigor
      Mortis.

PMID- 16992180
TI  - Proceedings of the Physiological Society, May 12, 1894. No. II.

PMID- 16992179
TI  - Note on the Chemistry of Muscle.

PMID- 16992181
TI  - On the Response of the Chick, before and after Hatching, to Changes of External
      Temperatuee.

PMID- 16992182
TI  - Haematoporphyrin in Normal Urine.

PMID- 16992183
TI  - A Simple Form of Gas Pump.

PMID- 16992185
TI  - Note on the Comparative Antiseptic Action of the Phenyl-substituted Fatty Acids.

PMID- 16992184
TI  - On the Action of Certain Substances on the Hearts of Daphniae.

PMID- 16992186
TI  - On the Effects of the Kneading of Muscles upon the Circulation, Local and
      General.

PMID- 16992187
TI  - Further Researches on Eye Movements.

PMID- 16992188
TI  - Note on the Oxidising Powers of Different Regions of the Spectrum in Relation to
      the Bactericidal Action of Light and Air.

PMID- 16992189
TI  - The Time-relations of the Voluntary Tetanus in Man.

PMID- 16992190
TI  - Proceedings of the Physiological Society, Nov. 17, 1894. No. VI.

PMID- 16992191
TI  - Proceedings of the Physiological Society, Oct. 27, 1894. No. V.

PMID- 16992192
TI  - Notes on the Action of Chloro- and Cyano-Caffeine.

PMID- 16992193
TI  - On Methaemoglobin.

PMID- 16992194
TI  - On the Action of Certain Acids on Blood Pigment.

PMID- 16992195
TI  - The Influence of Saline Media on the Tadpole.

PMID- 16992197
TI  - A Contribution to the Study of Uroerythrin.

PMID- 16992196
TI  - Electrical Phenomena during Movements of the Iris.

PMID- 16992199
TI  - The Path of the Respiratory Impulse from the Bulb to the Phrenic Nuclei.

PMID- 16992198
TI  - The Effect of saturating Normal Urine with Certain Neutral Salts.

PMID- 16992200
TI  - Proceedings of the Physiological Society, 1895. Nos. I. II. III.

PMID- 16992202
TI  - On the Origin from the Spinal Cord of the Vaso-Constrictor Nerves of the Portal
      Vein.

PMID- 16992201
TI  - An Experimental Investigation of Eye Movements.

PMID- 16992203
TI  - Changes in Ganglion Cells from Birth to Senile Death. Observations on Man and
      Honey-Bee.

PMID- 16992205
TI  - The Proteids of Red Marrow.

PMID- 16992204
TI  - Nucleo-Albumins and Intravascular Coagulation.

PMID- 16992206
TI  - Experimental Note on Two Movements of the Eye.

PMID- 16992207
TI  - On the Mode of Action of Lymphagogues.

PMID- 16992208
TI  - On the Proteolysis of Crystallized Globulin.

PMID- 16992209
TI  - The Morphology and Distribution of the Wandering Cells of Mammalia.

PMID- 16992210
TI  - Proceedings of the Physiological Society, June 23, 1894. No. III.

PMID- 16992211
TI  - The Constituents of the Hypogastric Nerves.

PMID- 16992212
TI  - A Study of the Sense of Equilibrium in Fishes: Part II.

PMID- 16992214
TI  - Studies in Phloridzin Glycosuria.

PMID- 16992213
TI  - On the Anatomical Constitution of Nerves of Skeletal Muscles; with Remarks on
      Recurrent Fibres in the Ventral Spinal Nerve-root.

PMID- 16992215
TI  - On the Physiological Action of Pyridine.

PMID- 16992216
TI  - The Relation of the Respiratory Exchange of Cold-blooded Animals to Temperature.

PMID- 16992217
TI  - Note on Oxalates and Muscle-Rigor.

PMID- 16992218
TI  - Further Observations on the Secretory and Vaso-Motor Fibres of the Foot of the
      Cat, with Notes on other Sympathetic Nerve Fibres.

PMID- 16992219
TI  - Proceedings of the Physiological Society, Aug. 11, 1894. No. IV.

PMID- 16992220
TI  - Sodium-glucose interactions in the goldfish intestine.
AB  - 1. Everted sacs of goldfish intestine transfer glucose and water to their serosal
      surfaces and the total transfer is greater in the anterior intestine than in the
      intestinal bulb or rectum.2. Transmural potentials, with the serosa positive to
      the mucosa, were recorded from all parts of the goldfish intestine but were
      highest in the anterior intestine and the rectum. In both these areas the total
      potential was dependent partly upon the presence of glucose.3. Reducing the
      concentration of sodium bathing the mucosa of the anterior intestine reduced the
      glucose-evoked potential in a non-linear way. The steady-state potentials, with
      or without glucose, first increased and later decreased as the sodium
      concentration was further reduced.4. Reducing the concentration of glucose
      bathing the mucosa from 27 to 5 mM slightly increased the glucose-evoked
      potential. Further reduction of the glucose concentration caused the glucose
      evoked potential to fall.5. Phlorrhizin inhibited the glucose-evoked potential.
      The degree of inhibition was proportional to the log concentration of phlorrhizin
      over the range 2 x 10(-7)-6 x 10(-5)M. The steady-state potential with glucose
      present was lower than when glucose was absent at phlorrhizin concentrations, 6 x
      10(-6)-6 x 10(-5)M.6. The glucose-evoked potential increased rapidly over the
      temperature range 5-15 degrees C and more slowly from 15 to 30 degrees C. The
      steady-state potentials also increased with temperature, the rate of increase
      being greater when glucose was present. Below 15 degrees C the glucose
      independent potential was higher and above 15 degrees C lower than the steady
      state potential recorded with glucose present.7. These findings are discussed in
      terms of sodium-glucose interaction taking place at the luminal side of the
      mucosal cell, on the outside of the mucosal cell membrane.

PMID- 16992221
TI  - On the permeability of the presynaptic terminal of the crayfish neuromuscular
      junction during synaptic inhibition and the action of gamma-aminobutyric acid.
AB  - 1. The contribution of chloride to presynaptic inhibition of the crayfish
      neuromuscular junction during the action of gamma-aminobutyric acid (GABA) and
      the inhibitory transmitter was investigated. Chloride in van Harreveld's solution
      was replaced with propionate, acetate, methylsulphate or glycerophosphate and
      electrical changes were recorded intracellularly and extracellularly with micro
      electrodes.2. When the preparation was soaked in Cl-deficient solutions, the
      quantum content of the excitatory junctional potentials (e.j.p.s), calculated
      from the number of failures, was increased.3. The presynaptic inhibitory action
      of GABA was reduced or almost absent when the preparation was soaked in Cl
      deficient solution. In Cl-deficient solution the stimulation of the inhibitory
      axon showed little or no inhibitory action on e.j.p.s.4. If GABA was applied
      shortly after the outside solution was changed to the Cl-deficient one, the
      frequency of the spontaneous e.j.p.s was increased transiently.5. It is suggested
      that GABA or the inhibitory transmitter act on the presynaptic excitatory
      terminal and predominantly increase its permeability to chloride.

PMID- 16992222
TI  - The effects of hypothalamic implants of ovarian steroids on oestrous behaviour in
      rabbits.
AB  - 1. The brains of ovariectomized female rabbits which were anoestrous in behaviour
      when tested with vigorous males were implanted either bilaterally or unilaterally
      with 10% oestradiol benzoate in cholestrol.2. Rabbits with implants in the
      ventromedial-premammillary hypothalamus ca. 1 mm lateral to the mid line became
      highly oestrous in behaviour within 1-2 days of implantation and mated 100% of
      the times tested. Implants of blank tubing, cholesterol or progesterone in this
      area, or oestrogen implants elsewhere in the hypothalamus had no effect on sexual
      behaviour.3. The uteri of all females implanted with diluted oestrogen were
      atrophic and similar to those of castrate controls, indicating that the effects
      of hypothalamic implants on sexual behaviour were direct local effects of
      oestrogen on the C.N.S.4. Rabbits implanted bilaterally with undiluted oestradiol
      benzoate showed some slight systemic spread of the implanted oestrogen. Oestrous
      behaviour was evoked within an average of 3.4 days by implantation into a large
      hypothalamic area, presumably as a result of oestrogen diffusing from the site of
      implantation to the critical ventromedial-premammillary region.5. Injections of
      progesterone in dosages known to block oestrous behaviour in intact or oestrogen
      primed rabbits, failed to block this behaviour in females implanted with pure
      oestrogen in the ventromedial-premammillary hypothalamus.6. Implantation of
      progestins into the ventromedial-premammillary area in overiectomized rabbits did
      not usually inhibit oestrous behaviour induced by small threshold doses of
      systemically administered oestrogen. The possibilities that oestrogen and
      progesterone (1) interact in different areas of the C.N.S. or (2) compete for
      ;steroid receptors' in the ventromedial-premammillary hypothalamus are discussed.

PMID- 16992223
TI  - Some properties of the external activation site of the sodium pump in crab nerve.
AB  - 1. Methods are described for using the changes in respiration of intact Libinia
      nerve to follow the rate of energy utilization by the sodium pump in this
      tissue.2. Short tetani in 10 K(Na)ASW (artificial sea water in which Na is the
      major cation and the potassium concentration is 10 mM) increased the oxygen
      uptake which then declined exponentially. From the net influx of Na during the
      tetanus and the associated oxygen uptake, values between 1.9 and 3.4 were
      calculated for the Na: approximately P ratio. After longer tetani, the recovery
      curve was S-shaped.3. The pump was activated by potassium ions in the external
      medium and this activation was competitively inhibited by external sodium ions.
      The data are consistent with a Michaelis constant (K(m)) for external potassium
      of 1 mM and an inhibitor constant (K(i)) for external sodium of 60 mM.4. In
      activating the pump, K could be replaced by Tl(+), Rb, NH(4) and Cs ions; but, of
      the monovalent ions tested, sodium seemed to be unique in its inhibitory
      action.5. In sea waters containing 460 mM-Na, ouabain behaved like a mixed
      inhibitor of the pump, reducing both the maximum velocity and the apparent
      affinity for external potassium. At a given ouabain concentration, reducing the
      sodium content of the medium was without effect on the maximum rate of pumping;
      but the apparent affinity for potassium increased more steeply than in a ouabain
      free solution.6. The rate of energy utilization associated with pumping was
      unaffected by inclusion of quite high concentrations of sulphydryl-blocking
      agents in the external medium.

PMID- 16992224
TI  - The inhibitory action of noradrenaline and other monoamines on spinal neurones.
AB  - 1. L-Noradrenaline (NA), 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) were
      administered micro-electrophoretically to feline lumbar neurones while recording
      their spike potentials extracellularly.2. There was no evidence to suggest that
      NA acts as an excitatory transmitter in the spinal cord.3. NA had potent
      inhibitory effects on some interneurones as revealed by a depression of
      spontaneous and synaptic firing and on the firing to a local application of an
      excitant amino acid. The effects on Renshaw cells and motoneurones were less
      marked.4. The depressant actions of 5-HT were less marked than those of NA. ACh
      and carbamylcholine had depressant effects on some NA-sensitive interneurones but
      were invariably far less potent and on other NA-sensitive cells were completely
      inactive.5. NA had no detectable effect on the normal spike amplitude but when
      the action potentials were reduced by excessive depolarization then both NA and
      synaptic inhibition increased the spike amplitude; this effect could be due to a
      hyperpolarization of the cell membrane.6. There was a correlation between the
      distribution of NA-sensitive cells and the relative densities of NA-containing
      terminals in various layers of the grey matter.7. It was postulated that NA acts
      as an inhibitory transmitter released from the terminals of descending pathways
      in the spinal cord. Other possible mechanisms were discussed but lacked
      experimental support.

PMID- 16992225
TI  - Factors affecting the distribution of iodide and bromide in the central nervous
      system.
AB  - 1. Even when a steady level of (131)I(-) is maintained in the blood for long
      periods, the uptake by brain and spinal cord is very small, and the possibility
      that this is due to an active transport of I(-) from brain-tissue to blood has
      been examined.2. Most of the phenomena, however, can be explained on the basis of
      a slow passive diffusion across the blood-brain barrier associated with an active
      transport of (131)I(-) out of the c.s.f. across the choroid plexuses, so that,
      except possibly for the spinal cord, active transport from central nervous
      parenchyma into the blood need not be postulated. If it does occur, it
      contributes very little to the net exchanges between the three compartments,
      plasma, c.s.f. and extracellular fluid.3. The steady-state distribution of
      bromide between plasma and c.s.f. is normally such that the concentration in the
      c.s.f. is only some 70% of that in plasma; it has been shown that this is most
      probably due to an active transport of Br(-) across the choroid plexuses.

PMID- 16992226
TI  - The time course of early changes in the rate of tension development in
      electrically-stimulated frog toe muscle: effects of muscle length, temperature
      and twitch-potentiators.
AB  - 1. An RC circuit employing a piezo-electric crystal was used to differentiate the
      tension output of electrically stimulated frog toe muscle.2. The rate of tension
      development curves (dP/dt) usually displayed an initial step-wise increase in the
      rate of tension development, and often showed further discernible steps in
      tension acceleration. The successive stages of tension acceleration tended to be
      equal in duration, and approximated the length of the latent period (ca. 4 msec
      at room temperature). These observations suggest a synchronous turnover of the
      links between the myofilaments during the initial interval following stimulation,
      with an over-all cycle time at room temperature of about 8 msec.3. Lowering the
      temperature produced proportionate alterations in the duration as well as the
      magnitude of each successive phase of tension development, with a Q(10) of
      approximately 2.4. Characteristic changes in the pattern of tension generation
      were seen with alterations in muscle length, and at lengths greater than 120% of
      the standard length the irregularities in the dP/dt curves disappeared and the
      rate of tension development increased in linear fashion. This behaviour could be
      accounted for by the hypothetical S-filaments connecting the free ends of the
      thin actin filaments across the H-zone.5. The effects of nine twitch potentiators
      were studied. Only perchlorate produced prominent increases in the earliest phase
      of tension development and in maximum tetanus tension-properties expected with an
      increase in the excitation-induced release of calcium ion into the sarcoplasm
      (increased intensity of the ;active state').6. The time of onset of the increases
      in tension acceleration which were produced by twitch potentiators did not
      correlate with their capacity to lower the ;mechanical threshold', indicating
      that the amount of calcium released by the action potential is not necessarily
      altered by a shift in the membrane potential at which calcium release occurs.7.
      All potentiators studied proved capable of (a) augmenting the rate of increase of
      tension generation (slope of dP/dt curves) during their rapid phase, as well as
      (b) increasing the interval during which the dP/dt curves for twitch and tetanus
      coincide. These effects occurred separately. It is suggested that both of these
      effects may be explained on the basis of delayed removal of sarcoplasmic calcium
      ion, resulting in prolongation of the ;active state'.

PMID- 16992227
TI  - Observations on the isolated foetal sheep with particular reference to the
      metabolism of glucose and fructose.
AB  - 1. Isolated sheep foetuses of 72-146 days conceptual age (155-4840 g) have been
      maintained for periods up to 325 min on an artificial circuit where the placenta
      has been replaced by an oxygenator.2. Measurements made during the period of
      observation included heart rate, femoral arterial pressure, umbilical blood flow,
      blood gases and pH; plasma and urine concentrations of glucose, fructose, lactic
      acid, urea, alpha amino nitrogen and electrolytes.3. The circulatory, metabolic
      and renal conditions of the isolated foetus were found to be similar to those of
      the exteriorized foetus with intact placental connexions. However, in the later
      stages a terminal hypoxia developed. This was due to a progressive diminution in
      umbilical blood flow caused by umbilical arterial constriction.4. The young
      foetuses removed glucose from the circulation and seemed unaffected by the
      consequent hypoglycaemia. If the glucose removed was completely oxidized it would
      account for much of the estimated oxygen consumption. The blood glucose
      concentration in the older foetuses, on the other hand, did not fall and
      sometimes rose. Renal excretion of glucose was very small.5. Fructose was usually
      slowly removed from the circulation and under no conditions did a rapid removal
      occur. Renal excretion accounted for about half of the fructose disappearing from
      the apparent fructose space. It is therefore suggested that a small utilization
      of fructose occurs in foetal tissues but this could account for only a very small
      fraction of the estimated oxygen consumption.

PMID- 16992228
TI  - Analysis of some central actions of nicotine injected into the cerebral
      ventricles of cats.
AB  - 1. In unanaesthetized cats intraventricular injections of 2.5-10 mug nicotine
      produced blinking, narrowing of the palpebral fissures, retching, vomiting and
      asynchronous twitching of the ears. With larger doses (30-100 mug) the ear
      twitching was interrupted for a short time by laying back of the ears.
      Respiration first became laboured and deep, then rapid and shallow following
      which panting occurred. There was salivation, loud calling, micturition and
      defaecation. With still larger doses (300-1000 mug) there was torticollis, ataxia
      and blind charging sometimes followed by a clonic-tonic convulsion.2. In cats
      anaesthetized with chloralose only some of these effects followed the
      intraventricular injection of nicotine, i.e. the ear response, respiratory
      changes and salivation. In addition, the pinna reflex was facilitated.3. The ear
      response and the facilitation of the pinna reflex did not occur on perfusion of
      nicotine from a lateral ventricle to aqueduct. They result from an action on
      superficial structures in the cervical cord between C1 and C2. Applied to this
      region of the cord, nicotine produced the ear response within 10-60 sec,
      sometimes in concentrations as low as 1/100,000. Applied below C2, nicotine was
      ineffective.4. Transecting the cord below C2 or cutting the dorsal and ventral
      roots of C1, C2 and C3 bilaterally did not affect the ear response produced by
      topical application or by intraventricular injection of nicotine. Transection of
      the cord above C1 abolished it.5. Hexamethonium applied to the cervical cord
      between C1 and C2 inhibited the ear response and the facilitation of the pinna
      reflex whether produced by nicotine applied topically or injected
      intraventricularly.6. The salivation and the respiratory changes produced by
      intraventricular injections of nicotine did not occur when nicotine was perfused
      from a lateral ventricle to the aqueduct. They result from an action of the
      nicotine on structures situated superficially in the brain stem. Nicotine had no
      sialogogue or respiratory effect when applied to the region of the cord at which
      it produced an ear response, but perfused through the subarachnoid space from
      interpeduncular fossa to cisterna magna or injected into the subarachnoid space
      alongside the brain stem, it produced these effects.7. Hexamethonium perfused
      from interpeduncular fossa to cisterna magna inhibited the salivary secretion as
      well as the respiratory changes produced by nicotine similarly applied.8. The
      efferent pathway for the salivation is parasympathetic since it no longer
      occurred after cutting the chorda-lingual nerve or after intravenous atropine.9.
      Intravenous injections of nicotine also produced the ear response with
      facilitation of the pinna reflex, salivation and hyperventilation in the
      anaesthetized cat, but only the ear response and facilitation of the pinna reflex
      are central effects. The salivation and hyperventilation following intravenous
      injection are due to peripheral actions of nicotine.

PMID- 16992229
TI  - Rhythmic activity in a simulated neuronal network.
AB  - 1. A digital computer has been programmed to simulate a neuronal network
      consisting of eighty cells with the following characteristics:(a) All cells in
      the network had a set random probability of discharge when not affected by other
      cells. The probability of discharge was chosen as one system parameter (PD).(b)
      Subsequent to the firing of any neurone in the network, a certain number of other
      neurones underwent a change in their probability of discharge, consisting of an
      inhibitory period followed by a period of increased excitability. The changes of
      excitability mimic the changes of the membrane potential recorded for
      spontaneously rhythmically active cells in the animal thalamus.2. Starting the
      network, a typical transient response appeared, consisting of a burst-like
      activity. The initial activity was followed, first by random fluctuations of the
      number of active cells, later by periods of spontaneous rhythmic activity that
      had several characteristics in common with the type of spontaneous activity seen
      in the animal thalamus.3. The parameters which affected the rhythmic activity of
      the network most strongly were the degree of the post-inhibitory increase of the
      probability of discharge and the degree of distribution of the inhibition to
      neighbouring cells.4. The results are compatible with the inhibitory phasing
      theory advanced by Andersen & Sears (1964) to explain the occurrence of
      spontaneous rhythmic activity in the animal thalamus. However, before sufficient
      experimental knowledge is available, it is difficult to establish whether the
      rhythmic activity in the network is of the same type as that of the animal
      thalamus.5. A closer study of the parameters governing the behaviour of the
      simulated network has given indications of some parameters to be more closely
      investigated in future animal experiments.

PMID- 16992230
TI  - Release of vasopressin and oxytocin from isolated pituitary glands of adult and
      new-born rats.
AB  - 1. Pituitary glands of adult rats of both sexes, of lactating female and of new
      born rats, incubated in a Locke solution, release both oxytocin and vasopressin.
      The amount of hormones released, during a measured period of incubation, is
      related to the actual hormone content of the gland.2. Increasing the
      concentration of KCl in the incubation medium, with CaCl(2) present and in
      concentration of at least 2.2 mM, produces an enhanced release of both hormones
      from pituitary glands of adults, but does not affect the release of hormones from
      glands of new-born animals.3. Addition of ouabain to the incubation medium
      produces a marked increase of the release of the hormones from glands of both
      adult and new-born rats. This is accompanied by an extrusion of K ion and an
      influx of Na ion. The effect of ouabain on the hormone release and the shift of
      ions can be reversed by subsequent addition of adenosine triphosphate.4. The
      increased release of hormones produced by ouabain, in glands from new-born rats,
      is unaffected by the presence or absence of CaCl(2). In adults, however, the
      effect of ouabain, though present, is reduced in the absence of CaCl(2).5. It is
      suggested that in glands from adult animals, the hormones must be freed from
      their attachment on the protein-carrier, neurophysin and that this can be
      achieved by the entry of calcium ion into the cell. The subsequent secretion of
      the ;freed' hormones appears to be accompanied by a shift of ions across the cell
      membrane.6. In glands from neonates up to 3 weeks old, the absence of
      neurophysin, or its poor capacity for binding the hormones, explains the
      inability of calcium to operate in the same way as in the glands of adults. There
      is evidence suggesting that the secretion of the neurohypophysial hormones in the
      new-born animal consists mainly of their diffusion from the cells, without
      previous elution of the hormones as in adults.

PMID- 16992231
TI  - An excitatory action of adrenaline, noradrenaline, and 5-hydroxytryptamine on the
      spinal cord.
AB  - 1. Fasciculation was produced in the trapezius and sternomastoid muscles of
      anaesthetized cats by adrenaline, noradrenaline and 5-hydroxytryptamine (5-HT)
      put into the cisterna magna. Isoprenaline, similarly applied, was ineffective.2.
      Each of the three active amines was without effect when applied for a second time
      after the fasciculation in response to the first application had passed off, but
      5-HT was effective after adrenaline and, similarly, adrenaline after 5-HT.3.
      Fasciculation produced by adrenaline, but not by 5-HT, was inhibited by
      ergotamine or phenoxybenzamine, given intravenously.4. In producing
      fasciculation, the adrenaline appeared to be acting on or through the lateral
      aspect of the upper cervical cord, about the line of emergence of the roots of
      the spinal accessory nerve, mainly in C1 and C2.5. The electromyograms of the
      fasciculation due to adrenaline and 5-HT showed intermittent bursts of activity.
      After adrenaline, the bursts consisted of fewer spikes than after 5-HT. The
      intervals between consecutive spikes were 3.75-5 msec after either amine, and the
      bursts occurred irregularly, at frequencies between 7 and 12/sec.6. It is
      suggested that adrenaline and 5-HT have excitatory actions on the dendrites or
      somata of the spinal accessory motor neurones, and the possible role of these
      amines as synaptic transmitters in the spinal nucleus of the accessory nerve is
      discussed.

PMID- 16992232
TI  - Cobalt applied to the sensorimotor area of the cortex cerebri of the rat.
AB  - 1. In anaesthetized rats, the area of the cerebral cortex where the electrical
      response to stimulation of the fore or hind paw has a minimum latency was found
      to bear a fairly constant relation to bony landmarks of the skull. Reasons are
      given for accepting the site of minimum latency as being the area most closely
      associated with the periphery.2. In animals under anaesthesia, the cortical areas
      responding with minimum latency to fore- and hind paw stimulation are spatially
      distinct.3. Cobalt powder has been applied to one of the two cortical areas where
      the electrical response to contralateral fore- or hind paw stimulation is a
      minimum. The animals have been allowed to recover and the time course of the
      resulting muscular jerks has been followed.4. Jerks occur most frequently and
      earliest in the contralateral forelimb after the application of cobalt to the
      forelimb area of the cortex. When the cobalt is placed on the hind limb area,
      these jerks appear first and occur most frequently in the hind limb. This implies
      that the cortical areas most closely connected with fore and hind limbs are
      physiologically distinct in the absence of anaesthesia.5. The limb jerks start to
      appear after 24 hr, occur with increasing frequency until the 10th day and
      thereafter decline. The decline in jerking is attributed to the formation around
      the cobalt of a connective tissue capsule.

PMID- 16992233
TI  - Presynaptic inhibition evoked by muscle contraction.
AB  - 1. Contractions of flexor and extensor muscles of the knee and ankle were used to
      investigate presynaptic inhibition at the spinal level.2. Contractions evoked
      dorsal root potentials, and increased the excitability of the central terminals
      of group Ia, Ib and low threshold cutaneous primary afferent fibres.3. The
      monosynaptic reflexes recorded in response to stimulation of flexor or extensor
      muscle nerves were depressed, in the presence of strychnine hydrochloride 0.1
      mg/kg I.V., by the contractions.4. It is suggested that these presynaptic
      inhibitory effects are largely due to the activation of Golgi tendon organs by
      contraction.

PMID- 16992234
TI  - The origin of the glucose dependent increase in the potential difference across
      the tortoise small intestine.
AB  - 1. Experiments were carried out to investigate the origin of the glucose
      dependent increase in the potential difference (p.d.) across the isolated
      intestinal mucosa of the tortoise.2. In addition to glucose, galactose, alpha
      methyl glucoside, 3-0-methyl glucopyranose and sucrose also increased the
      transepithelial potential difference. There was no increase with either fructose
      or mannose.3. The use of micro-electrodes demonstrated that the change in the
      p.d. due to the presence of glucose was wholly accounted for by the increase in
      the p.d. across the serosal face of the epithelial cells.4. Diffusion potentials
      were produced across the isolated mucosa by varying the ionic composition of
      either the mucosal or serosal fluids. However, there was no reduction of the
      glucose dependent increase in the p.d. when the ionic concentration gradients
      across the serosal face of the cell were reversed.5. These results suggest that
      the increase in the p.d. associated with the active transfer of sugars across the
      small intestine was due to the presence of an electrogenic ion pump at the
      serosal face of the epithelial cell.

PMID- 16992235
TI  - Contractures in a superfused frog's ventricle.
AB  - 1. A new perfused preparation of frog's ventricle is described, whose main
      advantage is that there are short diffusion distances between the cells and the
      washing fluid.2. This preparation responds within a few seconds to alterations in
      sodium, potassium or calcium concentration, or alteration in the osmotic pressure
      of the bathing fluid. The speed of these alterations is consistent with the
      diffusional distances involved measured histologically.3. On depolarizing the
      preparation with Ringer + excess potassium, tension development starts at about 
      25 mV and is still increasing at -8 mV (the lowest voltage studied). As in
      earlier experimetns in frog ventricle (Niedergerke, 1956b) and in skeletal muscle
      (Hodgkin & Horowicz, 1960) the relation between potential and tension is very
      steep.4. Sodium free contractures (Luttgau & Niedergerke, 1958) are very rapid in
      onset with this preparation. To maintain the tension developed, a rapid rate of
      washing is necessary for 1-2 min. After this, slow washing is sufficient. It is
      proposed that this is due to the leaching out of cellular sodium.5. In fresh
      preparations the twitch and maximum K contracture are of similar size when
      stimulated at 30/min in 1-2 mM-Ca. With the onset of hypodynamia the twitch
      tension falls, but the K contracture remains unaltered. In hypodynamic ventricles
      the sensitivity of the twitch to the ratio [Ca]/[Na](2) declines, whereas that of
      the K contractures remains unaltered. Hypodynamia therefore does not affect the
      contractile elements themselves.6. During the staircase phenomenon the K
      contracture and twitch size alter in a similar manner, as previously described by
      Niedergerke. The sodium free contracture, however, remains unaltered. This tends
      to favour the hypothesis that the staircase phenomenon is due to effects at the
      cell membrane rather than in the cell interior.7. Maximum K contractures occur at
      a [Ca]/[Na](2) ratio of about 0.7 x 10(-4) mM(-1), a figure similar to that
      obtained in earlier experiments (Luttgau & Niedergerke, 1958).8. The length
      tension curves of K contractures are similar to those previously described for
      heart muscle, using single twitches to generate tension.9. Application of K free
      solutions produced no rapid contractures in this preparation.

PMID- 16992236
TI  - The threshold conditions for initiation of action potentials by excitable cells.
AB  - 1. The relation between the strength and duration of a just threshold stimulus
      (strength-duration curve) is analysed for an excitable membrane polarized
      uniformly and for an excitable cable polarized at one point.2. The effect on the
      strength-duration curve of non-linearity in the membrane current-voltage curve
      has been analysed. The strength-duration curve can be derived if the membrane
      current-voltage relation is independent of time. The effects of changes in the
      current-voltage curve with time due to the existence of a finite membrane
      activation time and membrane accommodation are analysed.3. The strength-duration
      curve for the Hodgkin-Huxley membrane equations (Hodgkin & Huxley, 1952) is
      compared to that of Hill's (1936) two-time constant model.4. The relation between
      membrane current-voltage curves and those for a point-polarized cable are derived
      for the steady-state condition. The cable properties tend to linearize the
      current-voltage curve and to sharpen the voltage threshold.5. The strength
      duration curve for a point-polarized cable whose membrane obeys the Hodgkin
      Huxley equations is computed numerically. There is an additional large effect on
      the cable strength-duration curve arising from the redistribution of charge
      during passage of a constant current; and the resulting strength-duration curve
      lies within the range of curves predicted by Hill's model.6. The conditions
      required for a constant charge threshold (Hodgkin & Rushton, 1946) are shown to
      be satisfied for short, intense stimuli applied to a cable at one point.7. The
      results are discussed with reference to the experimental studies available.

PMID- 16992237
TI  - Active sodium transport by the colon of Bufo marinus: stimulation by aldosterone
      and antidiuretic hormone.
AB  - 1. The isolated colon of Bufo marinus transports sodium actively from the mucosal
      (lumen) to the serosal side, and this transport is expressed quantitatively by
      the short-circuit current.2. Upon dilution of sodium in Ringer solution on the
      mucosal side of the preparation, short-circuit current remained a fair expression
      of sodium transport from mucosa to serosa.3. In view of this, the relation
      between short-circuit current and dilution of sodium of the luminal side was
      examined. This relation was curvilinear, which suggests the intervention of a
      saturable step in the transfer of sodium from lumen to serosal surface of
      colon.4. The relation between short-circuit current on the one hand, and the
      amount of sodium drawn from the luminal side and recovered in the membrane
      (;active sodium transport pool') on the other hand, appeared (almost) linear
      instead. This is meant to indicate that the ;pump' operates far from capacity.
      Hence, the observed saturation of sodium transport, when concentration of sodium
      on the mucosal side was increased, probably occurs at the mucosal border of the
      preparation.5. After treatment with aldosterone, the ;active sodium transport
      pool' and short-circuit current increased to the same extent, from which it is
      inferred that the hormone merely allows sodium easier access to the ;pump' which
      would react in proportion. Consequently, no direct influence of aldosterone on
      the ;pump' proper need be postulated.6. Upon exposure of the colon to
      antidiuretic hormone, there were (modest) increases of short-circuit current and
      of osmotic water flow across the wall of the organ.

PMID- 16992238
TI  - The specific influence of carbon dioxide and carbamate compounds on the buffer
      power and Bohr effects in human haemoglobin solutions.
AB  - 1. The difference of pH (DeltapH) between human deoxygenated haemoglobin (Hb) and
      oxygenated haemoglobin (O(2)Hb) solutions when equilibrated with physiological
      pressures of carbon dioxide is (experimentally) much less than previously
      supposed.2. This smaller DeltapH is in contradiction to Wyman's (1948)
      theoretical calculations, wherein no allowance was made for the specific effect
      of carbamino-compounds on the amount of base neutralized by haemoglobin. Other
      previous authorities have also neglected this factor, which when properly allowed
      for restores the role of carbamino-compounds in CO(2) transport practically to
      that previously estimated by Ferguson & Roughton (1934a, b).3. At a given pH and
      P(CO(2) ), more CO(2) is bound by Hb solutions than by O(2)Hb, the difference
      increasing with pH. This result provides further, and seemingly decisive,
      evidence that the bound-CO(2) in the blood other than HCO(3)- (i.e. x-bound
      CO(2)) is oxygen-linked.4. According to a modified form of the Henderson
      Hasselbalch equation for haemoglobin solutions [Formula: see text]. The value of
      pK(1)' is the same in Hb as in O(2)Hb solution and from the data in 3 is found to
      have the value 6.15 at 37 degrees C.5. The difference between the titration
      curves of O(2)Hb and Hb (DeltaX), at a given pH had been hitherto supposed to be
      the same in presence of CO(2) as in its absence. Our experiments show, however,
      that DeltaX is less in presence of CO(2) and at pH > 7.5 may even change sign.
      This paradoxical effect is also explicable, at any rate semi-quantitatively, by
      the effect of carbamino compounds on the buffer power, according to the theory
      put forward in the paper.6. The results show that the buffer power (dB/dpH) of
      haemoglobin solution under physiological conditions is 20-30% greater than
      previously estimated, and this also is in line with the new theory.7. In graphs
      of total CO(2) versus P(CO(2) ) in haemoglobin solutions (or blood) it has been
      customary to suppose that points on straight lines radiating from the origin are
      points of equal pH. Our data, however, show that the iso-pH lines drawn through
      the experimental points in the pH range, 7.2-7.4 do not, when produced as
      straight lines, pass through the origin, but intercept the P(CO(2) ) axis
      significantly to the right thereof.8. Calculations indicate that most of the x
      bound CO(2) in haemoglobin solutions at pH 7.2-7.4 and at 37 degrees C can be
      accounted for by carbaminobound CO(2) without the need of postulating the
      existence of appreciable amounts of yet other forms, i.e. y-bound CO(2), in this
      range.

PMID- 16992239
TI  - Short latency activation of pyramidal tract cells by Group I afferent volleys in
      the cat.
AB  - 1. The contralateral bulbar pyramids were explored with low impedance micro
      electrodes in cats anaesthetized with chloralose to reveal the effect of Group I
      afferent volleys (deep radial nerve of the forelimb) on pyramidal tract (Pt)
      cells.2. Low rate (0.5/sec) stimulation of Group I afferents produced small
      responses (5-30 muV) in the bulbar pyramid which could be detected only with
      response averaging methods. The responses appeared with an initial latency of 7.0
      11.2 msec and reached peak amplitude in 15.7 msec (mean latency). The pyramidal
      tract origin of the potential was demonstrated by its depression at stimulus
      rates above 1-2 sec and its disappearance at rates above 4/sec.3. Recordings of
      neurones in the Group I cortical projection zone of the posterior sigmoid gyrus
      revealed that several types of cells, including Pt cells, were activated by Group
      I afferent volleys.4. Pt cells responding to Group I afferent volleys frequently
      received convergent actions from low threshold cutaneous nerve volleys.5.
      Averaged response recordings from electrodes positioned in the medial portions of
      the lateral funiculus of the spinal cord at the level of C(2), revealed a
      response to Group I afferent volleys as early as 7.4 msec which possessed the
      same characteristics as the relayed response to Group I in the bulbar pyramids.
      Some Pt cells, activated by Group I volleys orthodromically, could also be
      antidromically activated by stimulation of the recording site in C(2).6. It was
      concluded that group I afferent volleys can influence, after short latencies, Pt
      and non-Pt cells and that some of these Pt cells gave rise to axons incorporated
      in the corticospinal tract.

PMID- 16992240
TI  - Chemosensitivity of cardiac muscle.
AB  - 1. Measurements of contractions, conduction velocity and intracellular potential
      were made on isolated rabbit atria under four sets of conditions: high
      bicarbonate/high CO(2) (HH), low bicarbonate/low CO(2) (LL), high bicarbonate/low
      CO(2) (HL) and low bicarbonate/high CO(2) (LH). The ratio high/low was the same
      for the bicarbonate and CO(2) concentrations, so that HH had the same pH as LL.2.
      Acid solutions caused a fall of a few mV in the resting potential, but not in the
      overshoot. They reduced conduction velocity and rate of rise of the action
      potential. They depressed contractions, but prolonged the tail of the action
      potential.3. Alkaline solutions caused the converse changes, but, with the
      exception of the effect on the duration of the action potential, the relation
      with pH was markedly alinear, in that a rise in pH had much less effect than an
      equivalent fall.4. Statistical tests were devised to decide whether the observed
      changes were associated primarily with pH, P(CO(2) ) or bicarbonate. By far the
      strongest association was with external pH. Changes in P(CO(2) ), per se, had no
      significant effect.

PMID- 16992241
TI  - Membrane potential measurement in cells of the adrenal gland.
AB  - 1. Recordings of transmembrane potentials have been made in vitro from the cells
      of the adrenal gland using glass micro-electrodes.2. There was only a small
      species variation in the mean membrane potential of the cortical cells of the
      rabbit, rat and kitten; 66.2, 70.5, and 71.4 mV respectively.3. The membrane
      potential of cortical cells was dependent upon the external potassium
      concentration, [K](o). Raising [K](o) above the normal concentration of 4.7 mM by
      addition of KCl decreased the membrane potential; lowering [K](o) from normal
      increased it. The decrease in membrane potential was still evident when chloride
      was replaced by sulphate. Increasing [K](o) 10-fold decreased the membrane
      potential of rabbit cortical cells by 44 mV and of kitten cortical cells by 50
      mV.4. The mean membrane potential measured in medullary chromaffin cells was for
      the rabbit 24.2 mV, rat 20 mV, and kitten 31.7 mV. The potentials of medullary
      cells were much less affected by changes in [K](o) than were cortical cell
      potentials.5. Age had little influence upon either cortical or medullary membrane
      potentials of adrenal glands, at least in early life.

PMID- 16992242
TI  - Steroid production and membrane potential measurement in cells of the adrenal
      cortex.
AB  - 1. The relation between corticosteroid production and the cellular membrane
      potential of adrenocortical cells has been investigated using a flow system for
      the incubation in vitro of adrenal glands from neonatal rabbits. Corticosteroid
      production by the adrenal cells was determined by a fluorescence method; membrane
      potentials were measured with glass micro-electrodes.2. Adrenocorticotrophic
      hormone (ACTH) increased corticosteroid production without altering the membrane
      potential of the adrenocortical cells. Conversely, a 5-fold increase in [K](o)
      did not increase corticosteroid production but decreased the cellular membrane
      potential. The increase in [K](o) did not impair the stimulation of
      corticosteroid production by ACTH.3. The log dose-response relation between the
      concentration of ACTH in the incubation medium and the amount of corticosteroid
      produced by the adrenal tissue was linear.4. No evidence was found of a direct
      relation between the production of corticosteroid by adrenocortical cells and the
      cellular membrane potential. Indeed, the output of steroid appeared to be
      relatively independent of the polarization of the cell membrane.

PMID- 16992243
TI  - Current spread in the smooth muscle of the guinea-pig vas deferens.
AB  - 1. The membrane polarization in response to intracellular stimulation and
      external stimulation, the junction potentials evoked by nerve and field
      stimulation and the spontaneous junction potentials were studied in the guinea
      pig vas deferens.2. The responses to intracellular stimulation differed from
      those to external stimulation applied through a large electrode in the following
      ways: short time constant of the electrotonic potential; linearity of current
      voltage relation; all-or-none spike only in a small proportion of the cells; high
      critical firing level; short latency; weak tendency for repetitive activity
      during depolarization; and sharp spatial decay of the response.3. The difference
      between intracellular and external stimulation could be explained by differences
      in current distribution in the tissue, if many muscle fibres were aggregated in
      functional bundles, with three-dimensional cell-to-cell connexions, so that the
      membrane near an intracellular stimulating electrode was shunted by a large area
      of surrounding membrane.4. The time course of the junction potentials depended on
      the manner by which they were produced. The junction potential evoked by
      hypogastric nerve stimulation was recorded in every cell with almost the same
      amplitude. The spontaneous junction potential decayed very sharply with distance
      and the time course of the falling phase was about 10 times faster than that of
      the evoked junction potential.The difference between the time course of the
      junction potentials was also explained by the difference in current distribution
      in the tissue.

PMID- 16992244
TI  - An electrophysiological study of the effects of atropine and physostigmine on
      transmission to the guinea-pig vas deferens.
AB  - 1. The effects of physostigmine and atropine on transmission to the longitudinal
      musculature of in vitro preparations of the guinea-pig vas deferens have been
      examined using intracellular micro-electrodes.2. Atropine (5 x 10(-7) to 10(-6)
      g/ml.) increased the rate of decay of excitatory junction potentials (EJPs) in
      response to post-ganglionic stimulation.3. Physostigmine (5 x 10(-6) g/ml.)
      reduced the mean resting potential of the muscle cells from -60.5 to -51.5 mV and
      lowered the voltage of post-ganglionic stimulation necessary for initiation of an
      action potential in the muscle. In some but not all of the cells studied the time
      course of the EJP was markedly prolonged.4. At concentrations which did not alter
      the response to post-ganglionic stimulation (5 x 10(-7) to 10(-6) g/ml.),
      physostigmine caused fully facilitated EJPs to appear with the first pulse of a
      preganglionic train of stimulation.5. Atropine antagonized all the above effects
      of physostigmine.6. Physostigmine (5 x 10(-7) to 10(-6) g/ml.) also lowered the
      voltage of preganglionic stimulation necessary for initiation of an action
      potential in the muscle. This effect was not antagonized by atropine.7. The
      results are interpreted as being evidence for the existence of separate
      cholinergic and adrenergic motor fibres to the musculature of the guinea-pig vas
      deferens.

PMID- 16992245
TI  - The electroretinogram evoked by the excitation of human foveal cones.
AB  - 1. A 2 degrees test stimulus foveally fixed and viewed against a blue background
      (40 degrees in extent and producing 2.0 x 10(4) scotopic td of retinal
      illuminance) evokes a small voltage which can be recorded from the human eye with
      a conventional contact lens electrode if the test stimulus is flashed at a rate
      of 15 c/s, and the responses to at least several hundred flashes are averaged.2.
      The action spectrum of the response obtained in this way agrees reasonably well
      with the observer's psychophysical foveal luminosity curve.3. For the peripheral
      retina, the action spectrum is similar to that of the fovea when allowance is
      made for differences in screening macular pigment.4. Such responses diminish when
      the test stimulus is focused on to the peripheral retina and disappear when the
      test light is focused on the blind spot.5. Therefore, the response to the test
      light fixated centrally is the result of the excitation only of cones mainly, if
      not exclusively, in the fovea.6. When the intensity of the background is reduced
      by a factor of 10, the action spectrum shows evidence of the effect of excitation
      of rods in the blue part of the spectrum and of cones in the red. These red and
      blue responses add linearly when combined together, provided they are adjusted to
      coincide in phase.

PMID- 16992246
TI  - Mechanism of stimulation of aortic chemoreceptors by natural stimuli and chemical
      substances.
AB  - 1. Impulses were recorded in single fibres of aortic chemoreceptors of cats
      anaesthetized with chloralose. There was no demonstrable difference between the
      responses of the endings of medullated and non-medullated fibres respectively to
      any of the natural stimuli, such as hypoxia, reduction in blood pressure, or
      reduction in O(2) content. This indicates that the generator processes are
      qualitatively and quantitatively identical at the endings of both types of
      fibres.2. Most of the endings were practically silent while ventilating the lungs
      with air. The maximum frequency of discharge averaged over 4-10 sec while
      ventilating the lungs with 4% O(2) ranged from 1.5 to 24 impulses/sec; in most
      fibres (twenty-one out of twenty-six endings) it was less than 12 impulses/sec.3.
      All the chemoreceptors tested were considerably stimulated following
      administration of 0.2 or 2% CO at a time when the O(2) content was greater than 4
      ml./100 ml.4. All the chemoreceptors were markedly and rapidly stimulated
      following circulatory arrest while the cat was ventilated with air. This
      stimulation fell considerably within 3 min of circulatory arrest. Very little or
      no excitation followed circulatory arrest while ventilating the cat with pure
      N(2). These results suggest that excitation following circulatory arrest is not
      produced by a metabolite.5. There was a remarkable difference between the
      sensitivities of endings of medullated and non-medullated fibres to drugs. The
      former were either unaffected by relatively large doses of ACh (100-200 mug) or
      phenyl diguanide, or if they were stimulated, the excitation so produced was much
      less than that produced in endings of non-medullated fibres. This supports the
      hypothesis that drugs produce their effects by an action at the regenerative
      regions of the endings, i.e. regions where the nerve impulse is initiated
      (Paintal, 1964). It also indicates that ACh is not likely to be a transmitter in
      the normal processes of excitation of chemoreceptors.6. A mechanism of
      stimulation of chemoreceptors not involving metabolites is presented.

PMID- 16992247
TI  - The action of extracellular cations on the release of the sympathetic transmitter
      from peripheral nerves.
AB  - 1. The noradrenaline stores in the sympathetic nerve endings of the cat colon
      were labelled in vivo with (+/-)-[7-(3)H]noradrenaline (500 muc, 11.3 mug)
      injected 3 hr before killing.2. The colon was removed and immersed in an organ
      bath containing Krebs solution. The vascular bed was perfused from the inferior
      mesenteric artery to the colic vein.3. The effects of Ca(2+), Ba(2+) and Mg(2+)
      on the output of [(3)H]noradrenaline and [(3)H]metabolites in the venous effluent
      were measured before and after electrical stimulation of the post-ganglionic
      inferior mesenteric nerves at 10 impulses/sec.4. Nerve stimulation increased the
      efflux of [(3)H]noradrenaline when the perfusion fluid contained Ca(2+).
      Variations in Ca(2+) concentration (1.5-10 mM) did not affect this response.5.
      Removal of Ca(2+) from the fluid passing through the vascular bed (and therefore
      from the region of the sympathetic nerve terminals), abolished the output of
      [(3)H]noradrenaline in response to nerve stimulation. There was no change when
      phenoxybenzamine was added to prevent the binding of transmitter on to post
      synaptic receptors on the effector organ.6. The output of transmitter was not
      changed when Ca(2+) was present in the blood vessels of the colon even though it
      was removed from the solution in contact with the remainder of the tissue.7.
      Nerve stimulation released [(3)H]noradrenaline when Ba(2+) was used as a
      substitute for Ca(2+); Mg(2+) was not an effective substitute for Ca(2+) as then
      nerve stimulation did not increase the output of radioactive noradrenaline or
      metabolites.8. Ba(2+) also increased the resting output of [(3)H]noradrenaline in
      the absence of nerve stimulation. Addition of Ca(2+) or Mg(2+) did not change
      this spontaneous release but it was augmented by removal of Ca(2+).9. It is
      concluded that Ca(2+) is essential for release of the sympathetic transmitter by
      nerve stimulation but not for the spontaneous output that occurs in the absence
      of nervous activity. The site of action of Ca(2+) is considered to be the
      terminals of adrenergic fibres.

PMID- 16992248
TI  - The egress of oxygen from human HbO(2) in solution and in the erythrocyte.
AB  - 1. Spectrophotometric measurements, using the rapid-mixing constantflow and
      stopped-flow techniques, have been made of the rate of egress of oxygen from
      human HbO(2) in solution and in erythrocytes.2. By 1:20 dilution in a medium
      containing a high concentration of carbon monoxide k(4), the rate constant of the
      reaction Hb(4)O(8) --> Hb(4)O(6)+O(2) has been determined. At pH 7.4 and 20
      degrees C, k(4) in solution was 42.0 sec(-1) and within the intact cell 41.4 sec(
      1). The respective activation energies were 19.3 and 18 kcal.3. The rate of
      dissociation of HbO(2) to Hb, after mixing an erythrocyte suspension with
      Na(2)S(2)O(4), was identical, over at least 50% of the reaction, with the change
      of HbO(2) to HbCO above.4. An analysis of the data indicates that the cell
      membrane has little or no resistance to the passage of oxygen and the internal
      contents are effectively mixed.

PMID- 16992249
TI  - On the Escape of the Heart from Vagus Inhibition.

PMID- 16992250
TI  - The Relation of the Action of Carbonic Oxide to Oxygen Tension.

PMID- 16992251
TI  - On the Exchange of Blood-Gases in Brain and Muscle during States of Rest and
      Activity.

PMID- 16992252
TI  - The Physiological Effects of Extracts of the Suprarenal Capsules.

PMID- 16992254
TI  - Note on Regeneration of Prae-Ganglionic Fibres of the Sympathetic.

PMID- 16992253
TI  - On the Physiological Action of Extracts of Pituitary Body and certain other
      Glandular Organs: Preliminary Communication.

PMID- 16992255
TI  - Proceedings of the Physiological Society, 1895. No. IV.

PMID- 16992256
TI  - The Intravascular Coagulation produced by Synthesised Colloids.

PMID- 16992257
TI  - Nucleo-Proteids: Supplementary Paper.

PMID- 16992258
TI  - On a Supposed Action of Distilled Water as such on certain Animal Organisms.

PMID- 16992259
TI  - Towards the Ideal Artificial Circulating Fluid for the Isolated Frog's Heart:
      Preliminary Communication.

PMID- 16992260
TI  - On Intra-Cranial Pressure and the Cerebral Circulation: Part I. Physiological;
      Part II. Histological.

PMID- 16992262
TI  - Proceedings of the Physiological Society, 1895. No. V.

PMID- 16992261
TI  - The Effect of Variations in External Temperature upon the Output of Carbonic Acid
      and the Temperature of Young Animals.

PMID- 16992263
TI  - The Normal Absorption of Fat, and the Effect of Extirpation of the Pancreas on
      it.

PMID- 16992265
TI  - The Electrical Response to Stimulation of Muscle, and its Relation to the
      Mechanical Response.

PMID- 16992264
TI  - On the Absorption of Salt Solutions from the Pleural Cavities.

PMID- 16992266
TI  - The Influence of the Force of Gravity on the Circulation of the Blood.

PMID- 16992267
TI  - Synthesised Colloids and Coagulation.

PMID- 16992268
TI  - On the Innervation of the Pelvic and Adjoining Viscera: Part I. The Lower Portion
      of the Intestine.

PMID- 16992269
TI  - The Fall of Blood-pressure resulting from the Stimulation of Afferent Nerves.

PMID- 16992271
TI  - Further Observations regarding the antagonism between Calcium Salts and Sodium
      Potassium and Ammonium Salts.

PMID- 16992270
TI  - On Transpiration of Carbon Dioxide through the Skin of the Frog.

PMID- 16992272
TI  - The Action of Carbonic Oxide on Man.

PMID- 16992273
TI  - A Method of Detecting and Estimating Carbonic Oxide in Air.

PMID- 16992274
TI  - Further Experiments on the Embryonic Heart.

PMID- 16992275
TI  - On the amount of Iron in Ordinary Dietaries and in some Articles of Food.

PMID- 16992277
TI  - Proceedings of the Physiological Society, November 9, 1895.

PMID- 16992276
TI  - The Wandering Cells of the Alimentary Canal.

PMID- 16992278
TI  - Pulmonary lymph flow and the uptake of liquid from the lungs of the lamb at the
      start of breathing.
AB  - 1. Lymph from the lungs of lambs and sheep was found to enter both the right
      lymph duct and the thoracic duct. Right lymph duct flow was collected by
      constructing a venous sac, the venous tributaries of which were ligated but which
      the right lymph duct entered; thoracic duct flow was collected by cannulating the
      duct. Lymph from sites other than the lungs was excluded from the collections.2.
      Measurements were made of the surface tension characteristics of lung extracts
      and of the liquid present in foetal lungs. These values were used together with
      gestational age and crown-rump length to designate the foetal lambs into mature
      and immature groups.3. Lymph flow from the lungs averaged 0.99 ml./kg body wt./hr
      in immature foetal lambs, and 1.81 ml./kg/hr in mature foetal lambs before the
      start of ventilation. Lymph flow from the lungs of spontaneously delivered new
      born lambs (mean age 51 hr) averaged 0.86 ml./kg/hr. In adult ewes right lymph
      duct flow averaged 0.11 ml./kg/hr and total lung lymph flow was estimated
      indirectly to be 0.33 ml./kg/hr. Calculated rates of protein flow in lung lymph
      (flow x protein concentration) were greater in foetal lambs than in adult
      sheep.4. Total thoracic duct flow averaged 2.48 ml./kg/hr in immature foetal
      lambs, 5.30 ml./kg/hr in mature foetal lambs, 3.65 ml./kg/hr in new-born lambs,
      and 2.92 ml./kg/hr in adult ewes.5. At the start of ventilation there was an
      increase in lymph flow from the lungs, which at 15-30 min reached a mean of 6.4
      ml./kg/hr in mature lambs and 2.6 ml./kg/hr in immature lambs. At the same time
      the protein concentration of lymph decreased but the calculated protein flow
      increased.6. The lungs of foetal lambs weighed more than the lungs of
      spontaneously delivered new-born lambs, and the difference could be accounted for
      by liquid which could be aspirated through the trachea of the foetal lamb. On
      ventilation of the lungs for 2 hr, without first allowing the escape of any lung
      liquid, lung weight measurements indicated that about 66% of the lung liquid had
      been taken up in mature lambs and about 50% in immature lambs.7. It was concluded
      that the rate at which lymph is formed in the lungs is greater per kilogram body
      weight in foetal than in new-born lambs and greater in them than in ewes. The
      increase in lymph flow at the start of ventilation could account for the removal
      of about 40% of the liquid present in the lungs of the mature foetus and about
      25% of the liquid in the lungs of the immature foetus.

PMID- 16992279
TI  - The effect of distending a pouch of the left atrium on the heart rate.
AB  - 1. A pouch has been prepared consisting of a part of the wall of the left atrium
      together with the left pulmonary vein-atrial junctions.2. An increase of
      perfusion pressure in the pouch caused a reflex increase in heart rate.3. The
      afferent path of the reflex was in the vagus nerves and the efferent path was in
      the sympathetic nerves.4. The receptors most likely to be stimulated by an
      increase in pressure in the pouch are those receptors situated in the
      subendocardium of the pulmonary vein-left atrial junctions.

PMID- 16992280
TI  - The effect of stress on the concentration of 3beta-hydroxypregn-5-en-20-one
      (pregnenolone) and pregn-4-ene-3,20-dione (progesterone) in the adrenal gland of
      the rat.
AB  - 1. Pregnenolone and progesterone were estimated in extracts from adrenal glands
      of rats by gas-liquid chromatography.2. In unstressed rats their concentrations
      were found to be smaller than that of corticosterone.3. Acute stress caused an
      increase in the concentrations of these steroids which paralleled that of
      corticosterone.

PMID- 16992281
TI  - Motor unit types of cat triceps surae muscle.
AB  - 1. Motor units, defined as including a motoneurone (cell body, dendrites and
      axon) plus the muscle unit innervated, have been examined in the triceps surae
      motor pool of pentobarbital anaesthetized cats.2. The technique of intracellular
      stimulation and recording which was used permitted measurement of the axonal
      conduction velocity, post-spike hyperpolarization duration and input resistance
      of individual motoneurones, and the correlation of these properties with the
      characteristics of the twitch and tetanus responses of the muscle unit innervated
      by the cell elicited by direct intracellular stimulation.3. On the basis of
      muscle unit speed of contraction, motor units were divided into two groups: (a)
      fast twitch, or F, type with twitch time to peak (TwTp) less than or equal to 30
      msec, and (b) slow twitch, or S, type with TwTp of 40 msec or greater. The twitch
      tensions (TwTen) produced by type F units were significantly larger (median value
      = 18 g) than the tensions generated by type S units (TwTen median value = 1.6 g).
      Type F muscle units had much higher tetanus fusion frequencies (median = 85
      pulses/sec) than the S type (median 25 pulses/sec), and tended to have smaller
      tetanus to twitch tension ratios (Tet/Tw) (median = 2.6) than type S units
      (median = 5.4).4. The gastrocnemius heads contained a mixture of F and S types of
      muscle units, the proportions found being about 3 to 1 respectively. Units
      encountered in the soleus muscle were uniformly of type S. The characteristics of
      gastrocnemius and soleus type S motor units were not identical but appeared to
      represent quantitative differences in units of the same qualitative type.5.
      Motoneurones innervating type F muscle units had faster axonal conduction
      velocities, shorter post-spike hyperpolarizations and lower input resistances
      than those supplying type S units. However, no combination of motoneurone
      properties alone was sufficient to separate unambiguously types F and S motor
      units.

PMID- 16992282
TI  - Periodic eye tracking in the monkey.
AB  - 1. Eye movements were measured in monkeys trained for visual tracking.2. In
      response to periodic square wave target movements, monkeys do not show a
      significant reduction in the latency of saccadic movements.3. Under similar
      conditions, human beings subconsciously reduce their latency and after several
      cycles are in step with the target.4. In response to sinusoidal targets, monkeys
      show a latency or phase lag which increases monotonically with frequency starting
      at 0.3 c/s. Human beings can remain in phase with the target at frequencies up to
      1.0 c/s.5. Hence, monkeys do not exhibit the human predictive tracking response.

PMID- 16992283
TI  - Analysis of the activity of one type of spontaneously discharging unit in the
      cortex cerebri of the anaesthetized rat.
AB  - 1. Extracellular records from one type of spontaneously active element in the
      cortex of rats anaesthetized with urethane have been analysed statistically.2.
      Intensity functions reveal that the frequency of discharge of a unit tends to be
      modulated periodically, the period being 1(1/2)-2 sec under fairly deep
      anaesthesia. When anaesthesia becomes lighter, long intervals occur rarely; the
      unitary discharge becomes less regular and the intensity function becomes flat.
      Variations in depth of anaesthesia are accompanied by changes in amplitude of the
      periodic modulation; the period of the modulation is not significantly altered.3.
      Summed interval histograms indicate that the long intervals are separated by
      groups of short intervals in a significantly regular fashion. The number of short
      intervals in a group varies from one to about fifteen, according to the mean
      frequency of discharge of the unit.4. Serial correlation coefficients reflect the
      observations of 2 and 3 above but indicate no additional serial correlation. The
      existence of long intervals obscures any serial patterning of short intervals
      during bursts.5. Simultaneous records from two units show that the periods of
      activity in the two units are highly synchronized.6. It is probable that all
      these features are due to a process which causes periodic synchronous
      excitability changes of all the spontaneously active elements of the type
      studied.

PMID- 16992284
TI  - The effect of adrenaline on the adenosine otriphosphate and creatine phosphate
      content of intestinal smooth muscle.
AB  - 1. The smooth muscle of guinea-pig taenia coli was used to investigate the
      relation between metabolic and physiological effects of adrenaline. Electrical
      and mechanical activity was recorded with the sucrose gap technique and, in
      parallel experiments, the concentration of energy-rich phosphate compounds,
      adenosinetriphosphate and creatine phosphate, (ATP and CP) in the tissue was
      determined.2. Adrenaline (in concentrations from 2 x 10(-9) g/ml. to 5 x 10(-8)
      g/ml.) increased the tissue content of energy-rich phosphate compounds. This
      effect was coincident with the physiological, inhibitory effect on electrical and
      mechanical activity.3. After anaerobic exposure of the tissue to substrate-free
      medium, the biochemical and the physiological effects of adrenaline were both
      abolished; both recovered after readmission of oxygen and/or substrate.4. In
      muscles depleted of glycogen in substrate-free medium, either by anoxia or by
      high temperature, adrenaline produced its stabilizing effect on the cell membrane
      and the increase in ATP and CP content when beta-hydroxybutyrate was the
      substrate, i.e. in the complete absence of carbohydrate from the medium and from
      the tissue.5. When adrenaline was applied simultaneously with the readmission of
      substrate, the ATP and CP content of pieces treated with adrenaline was greater
      than of control pieces, though the tension of both was zero. This indicates that
      the effect was not secondary to the muscle relaxation but was the result of
      increased ATP synthesis.6. The physiological and biochemical effects of
      adrenaline were both abolished by the same concentration of imidazole (0.05 M).7.
      Low concentrations of ATP (1 x 10(6)-5 x 10(-6)M)-like adrenaline-inhibited
      electrical and mechanical activity of the taenia. This effect was also abolished
      by imidazole.

PMID- 16992285
TI  - Oxygen consumption by the isolated smooth muscle of guinea-pig taenia coli.
AB  - 1. An apparatus is described for simultaneous measurement of oxygen consumption
      and electrical and mechanical activity of isolated smooth muscle preparations.2.
      The mean oxygen uptake by the isolated taenia coli of the guinea-pig was 10-20
      mul./g/min.3. In spontaneously active preparations, adrenaline (10(-8)-10(-7)
      g/ml.) caused, with the inhibition of electrical and mechanical activity, a
      reduction in oxygen uptake.4. After prolonged exposure to substrate free solution
      spontaneous activity ceased periodically. Adrenaline, when applied during a
      silent period, had no detectable effect on resting oxygen consumption, while
      readmission of substrate, either glucose or beta-hydroxybutyrate, increased
      oxygen uptake.5. Adrenaline did not modify the increased oxygen uptake during the
      initial recovery period when it was given simultaneously with the substrate.
      However, adrenaline shortened the time interval which elapsed from the addition
      of substrate until spontaneous activity was resumed, indicating an acceleration
      of the recovery process.

PMID- 16992286
TI  - Tension development by isolated muscle spindles of the cat.
AB  - 1. Tension developed by mammalian intrafusal muscle fibres stimulated directly
      with single or repetitive electrical pulses has been determined in sixteen
      isolated lumbrical muscle spindles of the cat's foot.2. On microscopic
      observation, contraction to single shocks was observed in ten preparations. In
      three of these preparations twitch-like records were obtained.3. In the
      preparations that ;twitched', the tetanic fusion frequency was 10 pulses/sec at
      20 degrees C.4. In the ;twitching' intrafusal fibres the magnitude of contraction
      increased with increase of stimulus strength.5. In one of these spindles, only
      ;slow' contractions were obtained at low stimulus strengths when it was
      stimulated repetitively at 100 pulses/sec. With increase in stimulus strength,
      such ;slow' contractions gave twitch-like responses towards the end of a period
      of repetitive stimulation.6. Tension changes were recorded from all preparations
      stimulated repetitively. With supramaximal stimuli, the usual frequency of
      stimulation at which intrafusal tension was recorded was 10 pulses/sec at 20
      degrees C. The magnitude of contraction increased progressively with increase in
      stimulus frequency.7. Larger intrafusal tensions and faster time courses of
      contraction were obtained when the electrodes were astride the capsular region
      than when they were over the inferior extracapsular region.

PMID- 16992287
TI  - Properties of motor units in fast and slow skeletal muscles of the rat.
AB  - 1. Three kinds of motor unit have been distinguished in soleus (SOL) and extensor
      digitorum longus (EDL) muscles of adult rats on the basis of differences in
      isometric twitch contraction times measured at 35 degrees C.2. SOL contains about
      thirty motor units of which about twenty-seven are slow and three are
      intermediate with average contraction times of 38 and 18 msec respectively.3. EDL
      contains about forty fast motor units with an average contraction time of 11
      msec.4. Average values for maximum isometric tetanic tension were 4.7 g for fast
      and slow units and 5.85 g for intermediate units.5. Average values for twitch
      tetanus ratios ranged from 0.2 to 0.227 for EDL muscles, SOL muscles and the
      three kinds of motor units.

PMID- 16992288
TI  - Circulatory responses of supine subjects to the exposure of parts of the body
      below the xiphisternum to subatmospheric pressure.
AB  - 1. Observations are reported on the effects of exposure of parts of the body
      below the level of the xiphisternum of supine subjects to a pressure 70 mm Hg
      below atmospheric for 1 min.2. The stress on the circulation was greater than
      when parts below the iliac crests were similarly exposed. Heart rate increased by
      15-20 beats/min, there was a sustained fall in arterial blood pressure, and
      forearm blood flow fell profoundly and in some subjects was reduced to below 0.1
      ml./100 ml. min.3. In arms that were sympathectomized, or had received an
      intraarterial infusion of an adrenergic blocking drug, the fall in forearm blood
      flow was much less and could be related to the fall in arterial pressure.4. When
      the suction was released there was a brief overshoot of arterial blood pressure
      and brief cardiac slowing. Forearm blood flow rose to reach a peak some 15 sec
      after the release.5. In the sympathectomized forearm on release of suction there
      was an immediate rise in blood flow which was proportionately much greater than
      the rise in arterial blood pressure.6. This rise was not due to circulating
      vasodilator substances or to the activity of cholinergic vasodilator nerves. The
      possibility that it was the result of a change in the tone of the resistance
      vessels occurring in response to the sudden change in transmural pressure is
      discussed.

PMID- 16992289
TI  - Intracellular autogenetic and synergistic effects of muscular contraction on
      flexor motoneurones.
AB  - 1. Intracellular records have been taken from cat motoneurones innervating flexor
      muscles of the hind limb. Contractions of the ankle flexors tibialis anterior and
      extensor digitorum longus were elicited by stimulation of the peripheral end of
      the cut L 7 ventral root and the reflex effects of these contractions were
      recorded in silent and repetitively firing motoneurones.2. Contraction usually
      produces a hyperpolarizing response inside flexor motoneurones. This
      hyperpolarization is tension-sensitive in the sense that when, at constant muscle
      extension, the strength of the contraction is increased, the magnitude of the
      inhibitory response is augmented.3. Increasing the resting length of the muscles,
      while using a stimulus of constant strength to the ventral root, causes this
      inhibitory response to increase in some cells. More often, however, the
      hyperpolarization caused by contraction is gradually reduced in duration and/or
      amplitude as the muscles are extended.4. Even with the muscles slackened, so that
      they develop no tension at their ends, contraction usually produces prominent
      hyperpolarization of the motoneurones.5. By passing polarizing currents or
      injecting chloride ions through the intracellular micro-electrode, the
      hyperpolarizing potentials produced by contraction of the slack and extended
      muscles are shown to be, at least in part, genuinely post-synaptic inhibitory
      events.6. When the neurone is fired repetitively by injected current, the ;silent
      period' in contraction corresponds to the hyperpolarization of the post-synaptic
      membrane.7. Monosynaptic testing of the flexor motoneurone pool has been used to
      confirm the essential features of the intracellularly recorded activity.8.
      Acutely spinalizing the animal increases the magnitude of the inhibitory
      responses caused by contraction.9. Recordings from dorsal root fibres show that
      Golgi tendon organs of the ankle flexors are very sensitive to contraction and
      are indeed often activated by the internal forces developed in a contracting
      slack muscle.10. A number of muscle spindles of the ankle flexors are activated
      by stimulation of the ventral root at a strength submaximal or just maximal for
      the alpha-motor fibres, despite the simultaneous unloading effect of the
      contracting extrafusal fibres. This spindle activation, which occurs mainly
      during the phase of tension development in contraction, is favoured by an
      increased extension of the muscle. Attempts were made to establish whether it is
      due to alpha-motor innervation of the receptors or to some mechanical interaction
      between the intra- and extrafusal muscle fibres.11. The possible central and
      peripheral causes of the changes in motoneurone excitability produced by flexor
      muscle contraction are discussed. It is suggested that tendon organs of flexor
      muscles strongly inhibit flexor motoneurones and that alpha-motor innervation of
      muscle spindles is likely to play a more prominent role in flexors than in
      extensor muscles.

PMID- 16992290
TI  - An electrophysiological study of some reticulo-ruminal and abomasal reflexes in
      sheep.
AB  - 1. In halothane-anaesthetized sheep in which reticulo-ruminal (gastric)
      contractions were present, nervous discharges have been recorded
      electrophysiologically in sixty-four single efferent gastric units (grouped in
      seven types) dissected from the mid-cervical region of the left vagus. An
      examination was made of the reflex effects on the efferent discharges of the
      procedures given in paragraphs 2-5.2. Under isotonic recording conditions the
      total discharge was reduced but the peak frequency of most types of unit was
      enhanced compared with the discharge recorded under control isometric
      conditions.3. Abolition of reticular contractions by the use of preganglionic and
      post-ganglionic blocking agents resulted in an efferent discharge pattern similar
      to that recorded under isotonic conditions.4. Sudden deflation or inflation of
      the reticulum at the start of a reticular contraction had an effect that depended
      on the initial volume of the reticulum. It could be either excitatory and/or
      inhibitory.5. Acidification of the abomasal contents reflexly enhanced the
      discharge in three of ten efferent gastric vagal units. An abomasal pH less than
      1.0 appears to be less important in providing an excitatory drive to the ;gastric
      centres' in halothane-anaesthetized sheep than in decerebrate sheep.6. It is
      estimated that the total reflex time is > 1.3 sec for reticulo-reticular reflexes
      and > 2.1 sec for reticulo-ruminal reflexes. The central reflex time is > 370
      msec.7. It is concluded that a tonic afferent input from ;in series' reticular
      tension receptors during the quiescent period of the primary (reticulo-ruminal)
      cycle provides a reflex drive to the ;gastric centres' and largely determines the
      rate and amplitude of the reticular and ruminal contractions.8. The enhanced
      afferent input, during a reticular contraction under isometric recording
      conditions, modifies the size, form and duration of the later phases in the
      contraction sequence of the reticulum and rumen. The reflex effects are
      predominantly excitatory at low and moderate levels of reticular tension and
      inhibitory at high levels.

PMID- 16992291
TI  - Cross-innervated mammalian skeletal muscle: histochemical, physiological and
      biochemical observations.
AB  - 1. Cross-innervation of the slow soleus and fast flexor hallucis longus or flexor
      digitorum longus muscles has been performed in new-born kittens and rabbits and
      in adult cats.2. The effects on the histochemical and structural properties of
      the muscle have been studied and compared with the changes in the contractile
      properties.3. Cross-innervation has produced a dramatic change in histochemical
      pattern in the fast muscles, with the development of areas of muscle fibres
      indistinguishable from normal soleus muscle. The converse change from the
      histochemical pattern of slow soleus to that of fast muscle has also occurred,
      but has been less consistent.4. It is concluded that the neural influence
      determining the contractile properties of fast and slow muscle also has a
      profound controlling influence on the structure and metabolic activity of the
      muscle fibres.5. No significant changes could be demonstrated biochemically in
      the ATPase activities of the fast and slow muscles following cross-innervation.

PMID- 16992292
TI  - Effects of physalaemin on some exocrine secretions of dogs and rats.
AB  - 1. Physalaemin, an endecapeptide recently found in the skin of the South American
      amphibian Physalaemus fuscumaculatus, possesses, besides a marked hypotensive
      action and a powerful sialogogic activity, also a stimulant activity on other
      exocrine secretions.2. Exocrine structures which were more potently stimulated by
      the peptide were lacrimal glands and exocrine pancreas. In the anaesthetized dog
      the threshold lacrimatory dose was 0.05-0.3 mug/kg; in the rat the threshold dose
      was 2.5-5 mug/kg. The minimum active dose on exocrine pancreas of the dog was
      0.05-0.5 mug/kg.3. Physalaemin did not influence the gastric acid secretion of
      the dog at the maximum tolerated dose (40 mug/kg). Gastric acid secretion of the
      rat was stimulated very little if at all.4. In the dog the peptide caused some
      changes in the bile flow which were connected more with contracture of the gall
      bladder than with a true secretory stimulant activity. In the rat the peptide was
      completely ineffective.5. The results obtained after administration of
      sympatholytic and parasympatholytic agents suggest that the action of the peptide
      is at least partly independent from the autonomic nervous system.

PMID- 16992294
TI  - A comparison of the nerve impulses of mammalian non-medullated nerve fibres with
      those of the smallest diameter medullated fibres.
AB  - 1. Filaments were dissected from the aortic nerve of cats and impulses recorded
      monophasically in vivo.2. The temporal characteristics of impulses of non
      medullated fibres were compared with those of medullated fibres with conduction
      velocities between 4.5 and 12 m/sec. There were no obvious qualitative
      differences between the two types of fibres and they appeared to belong to a
      homogeneous sample.3. In non-medullated fibres the rise time, fall time and
      absolute refractory period varied inversely with conduction velocity, the
      relation being similar to that in the medullated fibres. There was practically no
      difference between the temporal characteristics of the fastest non-medullated
      fibres and those of the slowest medullated fibres, a result which might throw
      light on the question why fibres below 1 mu in diameter are not medullated.4. The
      mean blocking temperature of sixteen non-medullated fibres was 4.3 degrees C, a
      value that was significantly different from the mean blocking temperature of
      sixteen medullated fibres (6.5 degrees C).

PMID- 16992293
TI  - The effects of changes in haematocrit on renal function.
AB  - 1. Acute changes in total body haematocrit were produced in anaesthetized dogs by
      the rapid infusion of packed red cells, dextran solution or hypertonic mannitol.
      A reduction of haematocrit resulted in a decrease in filtration fraction, and a
      rise of haematocrit in an increase in filtration fraction. A direct relationship
      between water reabsorption (relative to filtered load) and packed cell volume
      (P.C.V.) was also observed.2. It is suggested that the changes in filtration
      fraction accompanying changes in haematocrit are mediated largely by a passive
      alteration of efferent arteriolar resistance resulting from modifications of
      blood viscosity.

PMID- 16992295
TI  - Electrical potentials and ion concentrations across the gut of Cryptochiton
      stelleri.
AB  - 1. The electrical potential and concentration differences of Na, K, and Cl in the
      mucosal and serosal solutions of everted sacs of gut from Cryptochiton stelleri
      were determined.2. The parameters were used to determine if active ion transport
      was present in segments from the anterior and posterior intestine.3. The
      electrical potentials were of the order of 0.5 mV, serosa negative, in the
      anterior intestine, and 1 mV, serosa positive, in the posterior intestine. The
      potentials, although small, were significantly different from zero.4. The
      potentials of all segments responded to anoxia and incubation at different
      temperatures in a manner indicating that they were of active origin.5. Ions were
      accumulated against electrical potentials in some segments but did not respond to
      anoxia or incubation at different temperatures in a consistent fashion.6. It was
      concluded that active ion transport was present but no evidence for active
      transport of Na, K or Cl across the gut could be found.7. K leaked from the gut
      during incubation at non-physiological temperatures or during hypoxia and was
      removed upon restoration of physiological conditions.

PMID- 16992296
TI  - An examination of certain factors which might, or do, affect the vascular
      response to oxytocin.
AB  - 1. A number of different observations were made on anaesthetized rats and some
      dogs to try to discover why it is that oxytocin is a vasodilator in dioestrus and
      anoestrus, and develops constrictor properties in oestrus and following
      sympathectomy.2. In those circumstances in which oxytocin in small or moderate
      doses raises blood pressure in the rat, the pressor effect is eliminated if the
      hormone is given during an infusion of adrenaline. In this respect the rat is
      closely similar to the dog.3. It was confirmed in anaesthetized oestrous rats
      that intravenous eserine eliminated the pressor response to oxytocin, and it was
      found that prostigmine did not reduce or change it. Thus, it may be concluded
      that the effect of eserine depends on its central sympathetic stimulant action
      and not on a peripheral effect.4. Rats which had been acutely or chronically
      adrenalectomized responded normally to oxytocin and both eserine and adrenaline
      were able to reduce, though not wholly eliminate, the pressor type of response.
      These results indicate that neither the adrenal medulla nor the cortex is
      essential for the action of oxytocin, nor for a large part of the action of
      eserine and adrenaline.5. The plasma concentrations of sodium, potassium and
      calcium were studied in a number of conditions affecting the response to
      oxytocin, namely, dioestrus, oestrus, and after administration of oestrogens,
      progesterone, adrenaline, eserine, hexamethonium, and dihydroergotamine. The
      cation changes observed could not be correlated with the type of response to
      oxytocin. The only measure found to affect the response was raising the plasma Na
      concentration by the infusion of disodium hydrogen phosphate. This reduced the
      pressor effect of oxytocin seen in oestrous female rats and in oestrogen treated
      males. The pressor response returned before the plasma sodium had fallen to
      normal levels.6. The administration of the oxytocin analogue, tyrosine-methyl(2)
      oxytocin which has a high receptor affinity and a low intrinsic activity,
      prevented the pressor response to oxytocin of oestrous rats, and the vasodilator
      response in the hind limb vessels of normal dogs. It is concluded that there is
      probably a single receptor for oxytocin from which both the constrictor and
      dilator effects are initiated.7. Oxytocin exerted apparently normal effects on
      the systemic blood pressure of oestrous or dioestrous rats given the beta
      blocking agents pronethalol or propranolol.8. The present results, like previous
      ones, indicate that adrenaline is the factor linking both the gonadal state and
      the peripheral sympathetic nervous system with the type of response to
      oxytocin.9. An incidental observation was that male and female rats show
      differences in their response to sympathetic blocking agents and to a raised
      plasma sodium concentration.

PMID- 16992297
TI  - The gradient of electrical potential difference and of sodium and potassium of
      the gut contents along the caecum and colon of normal and sodium-depleted rats.
AB  - 1. The Na, K and water content of stools, and of gut contents removed from the
      terminal ileum, caecum and colon were determined in normal and Na-depleted rats
      and the p.d. across the colon wall measured at the site of removal of each
      specimen.2. During passage through the caecum and colon, especially the ascending
      segment of colon, the faecal Na and water content fell considerably, K content
      being unchanged in the normal rats and falling in the Na-depleted. Na
      concentration of the faecal water fell but K concentration rose owing to water
      absorption.3. Feeding normal rats with a sulphonated polystyrene resin caused a
      considerable Na loss in the stool, the ratio Na/(Na+K) being consistently greater
      than in rats not taking resin. Resin induced little Na but much K loss in Na
      depleted rats.4. The electrical p.d. across the colon wall varied little over the
      length of the caecum and colon in normal rats, rarely exceeding 20 mV, the serosa
      being +ve with respect to lumen. Potential difference measurements were greater
      in Na-depleted rats, and those of the caecum and descending colon were
      consistently higher than those of the ascending colon. There was a similar
      pattern in resin-fed rats but potentials tended to be higher.5. K concentration
      of the gut contents was always greater than could be accounted for if K were
      passively distributed across the colonic mucosa.6. It was concluded that: (i)
      active Na absorption was stimulated by Na depletion; (ii) K was probably actively
      transported into the colon lumen, and when unabsorbable anions were present in
      the gut K secretion was critically important in Na absorption; (iii) the
      elevation of p.d. associated with Na depletion was probably associated with the
      stimulated Na transport.

PMID- 16992298
TI  - Transport of sodium and secretion of potassium and bicarbonate by the colon of
      normal and sodium-depleted rats.
AB  - 1. Ascending and descending colonic segments of normal and Na-depleted rats were
      perfused in vivo with isotonic solutions of varying Na concentration and the
      unidirectional Na fluxes and secretion rate of K and bicarbonate and the
      transmucosal electrical p.d. were measured.2. Potential difference was greater in
      Na-depleted rats, especially towards the distal end of the descending colon. With
      reduction of luminal Na concentration, p.d. was reduced.3. The ascending and
      descending segments were similar in regard to Na transport except that the latter
      had lower passive permeability. Na depletion caused an increase of Na influx
      rate, Na net flux rate and Na exchange diffusion whilst the mucosal passive Na
      permeability decreased. These changes resulted in a reduction in the critical
      luminal Na concentration, i.e. the concentration at which the unidirectional
      fluxes were equal.4. K secretion rate was similar in the ascending and descending
      colon and was increased by Na depletion. In all rats, it was reduced when the
      luminal Na concentration was low.5. Bicarbonate secretion rate was unaffected by
      the Na depletion and all solutions remained isotonic during perfusion.6. The
      results confirmed that active Na transport was stimulated by Na depletion but
      indicated that this was probably not the only factor in the elevation of
      transmucosal p.d.

PMID- 16992299
TI  - Transport of potassium by the colon of normal and sodium-depleted rats.
AB  - 1. Ascending and descending segments of colon of normal and Nadepleted rats were
      perfused with solutions of differing KCl concentration. Net K flux, electrical
      p.d. and, in some experiments, unidirectional K fluxes were measured.2. Variation
      of luminal K concentration over the range 0-40 mM did not affect p.d. or K efflux
      rate.3. K secretion rate fell about 30% when Na-free choline chloride solution
      was perfused.4. Net flux was a linear function of the luminal K concentration,
      and fell as the latter increased. Na depletion increased K secretion rate and
      passive permeability of the mucosa to K. Adrenalectomy had the reverse effect.
      The luminal K concentration, associated with zero net K flux was much greater
      than expected if the colonic mucosa behaved passively with respect to K.5.
      Unidirectional fluxes determined when 5 mM-KCl was in the lumen showed that the
      ratio influx/efflux was much less than predicted by Ussing's flux ratio
      equation.6. It was concluded that K influx was due to simple diffusion and K
      efflux to diffusion and active transport, both processes being increased by Na
      depletion.

PMID- 16992300
TI  - The experimental induction of hypophosphataemia in goats using anion exchange
      columns.
AB  - 1. Inorganic phosphate was selectively removed from the circulating blood of five
      anaesthetized goats by means of columns of anion-exchange resin. Concentrations
      of other ions were unaffected by the column.2. Rates of inorganic phosphate
      extraction in excess of 5 m-moles/hr caused a fall in plasma inorganic phosphate
      of up to 50% in 30 min.3. In four of the goats the calculated inorganic phosphate
      mobilization rate rose sharply to a maximum between 5.8 and 12.7 m-moles/hr and
      then fell progressively as more phosphate was removed.4. During the course of the
      experiments a fall in blood pressure occurred, accompanied by a rise in blood
      glucose. The reasons for this are discussed.

PMID- 16992301
TI  - The effect of ouabain on the secretion of catecholamines and on the intracellular
      concentration of potassium.
AB  - 1. Perfusion of bovine adrenal glands with 0.1 mM ouabain is accompanied by a
      doubling of the spontaneous rate of release of catecholamines and by a 66%
      increase in the response to stimulation with carbamylcholine.2. Perfusion with
      ouabain (0.1 mM) reduces the intracellular content of potassium from 106 to 63
      mM.3. The effect of ouabain on catecholamine secretion is dependent upon the
      presence of Ca(2+) ions in contrast to the effect upon the potassium content
      which is not dependent upon the presence of calcium.4. Ouabain has no effect on
      the release of catecholamines from isolated chromaffin granules both in the
      presence and absence of Ca(2+) ions.5. A possible relationship between the
      secretion of catecholamines and the concentration gradient of potassium across
      the cell membrane is discussed.

PMID- 16992302
TI  - Effects of salt loading and haemodilution on the responses of perfused cat
      kidneys to angiotensin.
AB  - 1. Effects of single intra-arterial injections (0.1-1.0 mug) of angiotensin II
      have been observed on cat kidneys perfused with heparinized blood from heart-lung
      circuits.2. Angiotensin II always caused an abrupt decrease in renal plasma flow
      (R.P.F.) which reached maximum in 1-2 min and lasted over-all for only 3.5-4.0
      min. Glomerular filtration rate (G.F.R.) usually and filtration fraction (F.F.)
      always increased.3. Angiotensin II caused antidiuresis provided that the kidney
      had not been subjected either to salt loading or to haemodilution within the
      preceding 3 hr. These pretreatments converted the antidiuretic action of
      angiotensin into a diuresis.4. Angiotensin II raised the rate of Na excretion,
      the urinary concentration of Na and the urinary Na/K whether anti-diuretic or
      diuretic.

PMID- 16992303
TI  - The influence of the polar anastomotic vessels on autoregulation and the urinary
      excretion of water and sodium by perfused cat kidneys.
AB  - 1. Cat kidneys have been perfused from pump-oxygenator and from heart-lung
      circuits.2. Kidneys perfused from the pump-oxygenator circuit excreted more water
      and sodium and showed higher values for sodium: potassium in urine than kidneys
      perfused from heart-lung circuits. Renal plasma flow and the clearances of
      creatinine and p-aminohippuric acid were similar for preparations perfused by the
      two different methods.3. Dorsal and ventral polar anastomotic vessels appeared to
      communicate directly with sheaves of vasa recta in the kidneys of young cats
      through interlobar vessels.4. Ligature of these polar anastomotic vessels
      impaired autoregulation of blood flow in perfused cat kidneys.5. Open drainage
      from these polar vessels during perfusion increased the rates of excretion of
      water and sodium.6. Histological preparations made from kidneys perfused from
      pump-oxygenator and from heart-lung circuits for periods of 5-6(1/2) hr showed
      that the nephrons remain undamaged. The diameters of the tubules correlated with
      the rates of urine flow immediately before fixation.

PMID- 16992304
TI  - Hormonal actions of the heart and of lungs on the isolated kidney.
AB  - 1. An hormonal influence of the heart on the isolated kidney has been
      demonstrated by insertion of hearts into pump-oxygenator circuits during renal
      perfusions.2. This hormone is a steroid which is secreted from the heart into the
      cardiac venous blood in response to reduction in venous input. The steroid is
      extractable from heart muscle.3. The actions of the cardiac steroid resemble
      those of aldosterone but are of shorter latency. Renal blood flow (R.B.F.) and
      glomerular filtration rate (G.F.R.) rise; urine flow, Na-concentration and Na/K
      decrease.4. An hormonal influence of lungs on the isolated kidney is also
      demonstrated. This hormone is not a steroid. It is antidiuretic and Na-retaining:
      the concentration of urinary Na rises: Na/K remains unchanged.

PMID- 16992305
TI  - An analysis of facilitation of transmitter release at the neuromuscular junction
      of the frog.
AB  - 1. Experiments were done on Mg-blocked neuromuscular junctions of the frog to
      study in detail the magnitude and time course of facilitation of the end-plate
      potential (e.p.p.).2. When two shocks were applied to the motor nerve with an
      interval of 5 msec or less between them, the amplitude of the second e.p.p. was
      facilitated by approximately 100%. This facilitation decreased as the interval
      was lengthened.3. The facilitation could be separated into two components on the
      basis of the time course of its decay as the interval between the two shocks was
      increased. The first component decayed exponentially after the conditioning shock
      with a time constant of about 35 msec. The second became apparent 60-80 msec
      after the conditioning shock, rose to a maximum of approximately 15% at about 120
      msec and decayed thereafter with a time constant of the order of 250 msec.4. The
      growth of e.p.p. amplitude during short trains of repetitive stimulation at
      frequencies up to 100/sec and its subsequent decay could be predicted by assuming
      that the magnitude and time course of both components of facilitation were the
      same for every shock in the train and that these individual facilitatory effects
      summed linearly.

PMID- 16992306
TI  - Auditory responses of neurones in the lateral mesencephalic nucleus (inferior
      colliculus) of the Barbary dove.
AB  - 1. Auditory responses have been recorded from forty-five single neurones in the
      lateral mesencephalic nucleus of the dove, confirming the suspected auditory
      function of this nucleus.2. Most of the neurones with sustained responses to
      tones fell into three response-categories: inhibitory only, excitatory in a
      central range of frequencies with inhibition in adjacent frequency regions, and
      predominantly inhibitory with one or more relatively small excitatory regions.
      Seven of the neurones studied showed only transient responses: these had high
      thresholds or were restricted to a narrow range of frequencies.3. Responses to
      clicks were sometimes obtained, but were variable in different units and in a
      single unit were often dependent on repetition rate.4. Many properties of these
      neurones are similar to those in the cat inferior colliculus. The most notable
      difference is the existence in the dove of neurones with exclusively or
      predominantly inhibitory responses.

PMID- 16992307
TI  - A quantitative study of cutaneous receptors and afferent fibres in the cat and
      rabbit.
AB  - 1. The discharge in myelinated afferent fibres innervating hairs in anaesthetized
      cats and rabbits, dissected from the saphenous nerve, was recorded during
      controlled movements of the hairs.2. Three types of rapidly adapting afferent
      unit were found and they innervated three kinds of hair follicle-down hair, guard
      hair and tylotrich.3. The down hair units had low thresholds (critical slopes)
      and some of the guard hairs had the highest thresholds and least sensitivity to
      displacement.4. There was a good fit to a power function for the relation between
      velocity of displacement of a hair and the frequency of discharge in the
      corresponding afferent fibre.5. It is concluded that the rapidly adapting hair
      follicle receptors can function as efficient exact movement detectors.6.
      Tylotrich follicles were often associated with touch corpuscles, but there was
      independent innervation of the rapidly adapting tylotrich follicle receptors and
      the slowly adapting touch corpuscle receptors.7. The conduction velocities of
      large populations of myelinated cutaneous axons innervating cutaneous
      mechanoreceptors were measured in cats and rabbits.

PMID- 16992308
TI  - Effects of nerve cross-union on fast-twitch and slow-graded muscle fibres in the
      toad.
AB  - 1. A method is described for resolving isometric tetanic tension developed by
      fast-twitch and slow-graded components of heterogeneous toad muscles. This makes
      use of the difference in threshold for excitation of low threshold nerve fibres
      which normally innervate the fast-twitch muscle fibres and high threshold nerve
      fibres which innervate slow-graded muscle fibres.2. The sartorius muscle contains
      only fast-twitch muscle fibres whereas the posterior semitendinosus (PST)
      contains both fast-twitch and slow-graded muscle fibres, the latter contributing
      10-15% of the maximum isometric tetanic tension.3. Following surgical cross-union
      of nerve to sartorius and PST muscles, both the fast-twitch and slow-graded
      muscle fibre components of the PST are reinnervated by low threshold nerves
      originally innervating sartorius fast-twitch fibres, and sartorius fast-twitch
      muscle fibres are reinnervated by both low threshold and high threshold nerves
      formerly supplying the fast-twitch and slow-graded muscle fibre components of the
      PST.4. The characteristic mechanical responses of fast-twitch muscle fibres and
      slow-graded muscle fibres were not transformed up to 134 and 200 days
      respectively following nerve cross-union.5. PST nerve partially innervated the
      sartorius muscle whereas sartorius nerves completely innervated the PST muscle.
      Isometric tetanic tension declined markedly during repetitive indirect
      stimulation of cross-innervated sartorius muscles, whereas the tetanic
      contractions of cross-innervated PST showed a plateau of tension and resembled
      the response of normal muscles.6. Normal, cross-innervated and self-innervated
      PST muscles gave sustained contractures in the presence of acetylcholine whereas
      PST muscles denervated for 120 days gave phasic contractures similar to those of
      normal, cross-innervated and self-innervated sartorius muscles.

PMID- 16992309
TI  - Energy cost of tonic contraction in a lamellibranch catch muscle.
AB  - 1. The oxygen consumption of isolated anterior byssus retractor muscle (ABRM) of
      Mytilus edulis was measured during tonic contraction induced by acetylcholine
      (ACh).2. The respiration was measured with an oxygen electrode during 95 min,
      divided into one period of 5 min and six successive periods of 15 min.3. Tonic
      contraction induced a prolonged increase of the basal respiration that slowly
      diminished with a time course roughly similar to that of the tonic tension.4. For
      each period of measurement, the excess respiration over the resting level could
      be analysed into a constant amount and an amount that depended on the maintained
      tonic tension. The analysis was performed by fitting regression equations of the
      type Y = Q+bP, where Y is the excess respiration in n-moles O(2)/g.min, and P,
      the isometric tension (kg/cm(2)); term b of the equation expresses the amount of
      oxygen consumption directly proportional to the tonic tension.5. During the first
      20 min of contraction, terms b of the equations are not significant, and most of
      the excess respiration (terms Q) is independent of the tension. The oxygen
      consumed during this time is supposed to reflect the recovery metabolism for the
      energy cost of the development of the tension.6. From the 20th to the 80th min of
      contraction, terms Q are reduced and terms b are significant and constant. The
      excess respiration during this period is equal to 16.9 (+/-0.5) n-moles
      O(2)/g.min + P x 6.8 (+/-0.5) n-moles O(2)/kg.cm.min (+/-S.E. of the means, n =
      24).7. During a tonic contraction suppression of tension by a release reduced the
      oxygen consumption which increased again when tension was restored by stretching
      the muscle back to its original length. This confirmed the role of tension in
      determining the intensity of respiration during the catch.8. The oxygen
      consumption related to this tension restored by stretching the muscle, varied
      from 8.0 to 12.3 n-moles O(2)/kg.cm.min. These figures are of the same order of
      magnitude as the coefficient b obtained in the case of tonic contraction without
      modification of tension by length changes.9. These results are taken as a
      demonstration that the maintenance of tonic tension is an ;active' phenomenon
      with a metabolic counterpart.

PMID- 16992310
TI  - The distribution of monosynaptic excitation from the pyramidal tract and from
      primary spindle afferents to motoneurones of the baboon's hand and forearm.
AB  - 1. Intracellular records were obtained from motoneurones innervating muscles of
      the baboon's forearm and hand. Monosynaptic excitatory postsynaptic potentials
      (EPSPs) were elicited by stimulation of motor cortex (CM EPSPs) and peripheral
      nerves (Ia EPSPs).2. CM EPSPs were larger on average in motoneurones innervating
      intrinsic hand muscles and extensor digitorum communis (EDC) than in neurones of
      other forearm muscles.3. Among motoneurones of the median nerve, the CM EPSP
      tended to be larger for cells with more rapidly conducting axons than for those
      with more slowly conducting axons. Among motoneurones of EDC the opposite
      tendency was found.4. The afferent fibres responsible for the Ia EPSP nearly
      always had a lower stimulus threshold than that of motor axons in the same nerve.
      Some observations were made concerning the distribution of heteronymous Ia
      EPSPs.5. Among motoneurones of a given nerve, those with large Ia EPSPs tended to
      receive larger CM EPSPs than did cells in which the Ia EPSP was small.6. The
      results are discussed in relation to problems concerning the pyramidal control of
      hand and finger movement.

PMID- 16992311
TI  - Conduction velocity in proximal and distal portions of forelimb axons in the
      baboon.
AB  - 1. Peripheral nerves of the baboon's forelimb were stimulated at different sites,
      and the latencies of antidromic action potentials were measured in intracellular
      records from forelimb motoneurones.2. The conduction velocity of single motor
      axons was slower in the brachial plexus than in the nerves of the arm and
      forearm. This proximal slowing of conduction velocity was more marked for rapidly
      conducting axons than for the more slowly conducting ones.3. Gross recordings
      from dorsal and ventral roots showed that the conduction velocity was slower in
      the brachial plexus than in the arm for fast afferent as well as efferent nerve
      fibres.4. The proximal slowing of conduction velocity was shown to be due neither
      to errors of measurement nor to proximo-distal differences of temperature.

PMID- 16992312
TI  - Motor innervation, motor unit organization and afferent innervation of m.
      extensor digitorum communis of the baboon's forearm.
AB  - 1. One hundred and fifty efferent axons innervating m. extensor digitorum
      communis (EDC) were isolated in filaments of C7 and C8 ventral roots of baboons.
      Conduction velocities were measured antidromically by stimulating the muscle
      nerve and recording from the filaments, and fell into two groups: a fast (49-84
      m/sec) and a slow (22-41m/sec), presumably fusimotor group. The threshold for
      these latter axons exceeded the strength needed to elicit the maximal motor
      twitch.2. Stimulation of ventral root filaments containing slow axons produced no
      contractile tension in EDC.3. Stimulation of ventral root filaments containing
      fast-group axons elicited all-or-nothing twitches of motor units of EDC. The
      twitch tensions of 66.3% of the units were < 2.0 g wt.; only 8.7% were > 5.0 g
      wt. Tetanus-twitch ratios were 1.4-4.7 in a sample of 14 units. Contraction times
      were between 15 and 35 msec in 97% of the units. There was no correlation between
      contractile properties and axonal conduction velocity.4. Afferent volleys from
      the stimulated EDC nerve were recorded from C6 or C7 dorsal roots. The threshold
      was below the threshold for a just-detectable motor twitch in ten out of eleven
      baboons. Conduction velocity of the earliest component of the muscle afferent
      volley was 67-83 m/sec.5. The conduction velocities of twenty-eight spindle
      afferents, identified by their responses to linear stretches of EDC and by their
      unloading by maximal twitches, were all < 70 m/sec. Higher dynamic sensitivity
      tended to be associated with higher conduction velocity.

PMID- 16992313
TI  - The responses of goats to the experimental induction of hypocalcaemia with cation
      exchange columns.
AB  - 1. Ionic calcium was selectively removed from the circulating blood of three
      anaesthetized goats by means of columns of cation-exchange resin. Concentrations
      of other ions were not directly affected by the column.2. A calcium extraction
      rate of 0.35 m-equiv/min caused a fall in plasma total calcium of up to 40% in 35
      min. Plasma calcium concentration returned to normal within 2 hr of the end of
      calcium removal.3. Mobilization rates reached a maximum between 15 and 20 min
      after calcium removal commenced, declining rapidly after it had stopped.4.
      Removal of calcium by EDTA infusion results in a similar calcium mobilization
      pattern to that produced by Ca removal by ion-exchange.5. A smaller variation
      appears to exist between goats in maximum calcium mobilization rates than in
      maximum phosphorus mobilization rates and goats may be able to mobilize
      phosphorus relatively faster than calcium.

PMID- 16992314
TI  - Interaction between sodium and calcium ions in the process of transmitter release
      at the neuromuscular junction.
AB  - 1. The interaction between Na and Ca ions on quantal transmitter release at the
      frog neuromuscular junction has been studied, using intracellular recording and
      averaging of responses.2. At low calcium concentrations, partial withdrawal of Na
      ions increases end-plate potential (e.p.p.) amplitudes and quantal content (m)
      and decreases the amplitude of the miniature e.p.p.s (m.e.p.p.s). Under these
      conditions the relation between [Ca] and m is highly non-linear. When plotted on
      double logarithmic co-ordinates withdrawal of [Na] causes a nearly parallel shift
      of this relation.3. Mutual interaction occurs between Ca, Na and Mg in
      transmitter release. With a constant low [Ca] in the medium, withdrawal of [Na]
      produces a smaller increase in m when [Mg] is high, than when [Mg] is low.4. In
      the presence of normal [Ca] (1.8 mM), [Na] withdrawal decreases the amplitude of
      the e.p.p. and produces a small decrease in m.5. The results can be explained by
      assuming that [Na] reduction has two mutually opposing effects on transmitter
      release: it makes more sites available for the action of Ca, and it lowers the
      amplitude of the action potential in the nerve terminals. The former effect
      dominates at low, the latter at high, calcium concentrations.

PMID- 16992315
TI  - Rod/cone rivalry in pigment regeneration.
AB  - 1. The rod branch of the dark-adaptation curve was studied at two regions 1(1/4)
      degrees from the foveal centre (see inset, Fig. 2).2. One region had been
      bleached by red light, the other by blue of equal scotopic value.3. This equality
      was established by finding the rod increment threshold against the red or blue
      backgrounds: they were judged equal when they raised the rod threshold equally.4.
      If the bleaching exposure lasted 4 min or less, the rod dark-adaptation curves
      coincided, though the cone branches did not (since red bleached cones 80%, blue
      20%, but rods were bleached equally).5. If the bleaching exposure was prolonged
      to 16 min the rods recovered more slowly from the red bleach. And this difference
      was enhanced by a preliminary intense white exposure that bleached everything.6.
      The effect was due to the presence of cones since repeating the experiment at 15
      degrees from the fovea where cones are scarce virtually gave coincident rod dark
      adaptation curves.7. It follows that where cones are regenerating fast (from the
      80% red bleach) they extract from the space outside the cone cells some
      ingredient needed for rod regeneration, and after pronounced and prolonged
      bleaching, the lack of this ingredient slows rod recovery.8. Most probably the
      ingredient is 11-cis retinol returning from the pigment epithelium.

PMID- 16992316
TI  - The angular selectivity of visual cortical cells to moving gratings.
AB  - 1. Grating patterns were used to obtain a quantitative description of cells in
      the visual cortex of the cat whose response amplitude depended critically upon
      the orientation of the moving grating.2. In all such cells the impulse frequency
      was found to decrease linearly with angle on either side of an optimum angle (the
      preferred angle) until the response fell to zero or to a base frequency. The
      angular rate of change of response varied between cells and was expressed as the
      half-width at half amplitude (the angular selectivity).3. The angular selectivity
      of thirty-five cells was determined and more than half (nineteen) of these fell
      within the range 14-26 degrees .4. Fourteen cells responded optimally only when
      the grating was moved in one direction. Twenty-one cells responded optimally to
      two directions of movement 180 degrees apart, but the response in the two
      directions was not always equal.5. No significant correlation was found between
      the response amplitude at the optimum angle and the angular selectivity.6. The
      distribution of preferred angles did not show any difference between the oblique
      orientations and the vertical and horizontal orientations.7. These results are
      compared with a previous psychophysical estimate of angular selectivity.

PMID- 16992317
TI  - Quantitative estimation of 17alpha-hydroxypregn-4-ene-3,20-dione (17alphaOH
      progesterone) in adrenal venous blood and adrenal glands.
AB  - 1. A method is described for the accurate estimation of small quantities of
      17alpha-hydroxypregn-4-ene-3,20-dione (17alphaOH-progesterone) in blood and
      adrenal glands.2. The dog adrenal was found to secrete 17alphaOH-progesterone
      under conditions of operative stress at a rate of 5-10 mug/g tissue/hr. This is
      similar to the secretion rate of aldosterone.3. The secretion of 17alphaOH
      progesterone was decreased after hypophysectomy and increased in response to
      adrenocorticotrophic hormone (ACTH).4. The adrenal gland of the dog, the monkey
      and the guinea-pig was found to contain between 0.6 and 6 mug of 17alphaOH
      progesterone/g tissue. The concentration was usually somewhat smaller than that
      of pregnenolone or progesterone and between 1 and 20% of the concentrations of
      the glucocorticoids.5. A comparison of adrenal steroid contents and secretion
      rates under conditions of stress indicates a rate of synthesis in the order of 30
      40 n-moles of 17alphaOH-progesterone/g adrenal tissue/min.

PMID- 16992318
TI  - Activity of aortic chemoreceptors during electrical stimulation of the stellate
      ganglion in the cat.
AB  - 1. In anaesthetized cats, action potentials from aortic chemoreceptors were
      recorded during electrical stimulation of preganglionic sympathetic fibres to the
      decentralized right stellate ganglion. The rate of discharge in afferents in the
      ipsilateral but not in the contralateral aortic nerve increased when stimulus
      frequency was 4/sec or higher.2. The post-ganglionic fibres in the stimulated
      pathway originate in the right stellate ganglion. They leave the ganglion in the
      caudal limb of the ansa subclavia, and the results suggest that the ipsilateral
      aortic nerve and its branches distribute sympathetic fibres as well as afferents
      to aortic bodies.3. In contrast, the rate of discharge of chemoreceptor fibres in
      the contralateral aortic nerve fell as blood pressure increased during
      sympathetic stimulation. Sympathetic pathways to the aortic bodies can maintain
      or increase chemoreceptor discharge during hypertension elicited by sympathetic
      activation.

PMID- 16992319
TI  - On the Relationship of the Liver to Fats.

PMID- 16992320
TI  - On the Chemical Composition of Enamel.

PMID- 16992321
TI  - The Maximum Muscular Effort of the Horse.

PMID- 16992322
TI  - On the Passage of Sodium Iodide from the Blood to the Lymph, with some Remarks on
      the Theory of Lymph Formation.

PMID- 16992323
TI  - A Method for the Study of the Intestinal Absorption of Peptone.

PMID- 16992324
TI  - The Time of Contraction of the Papillary Muscles.

PMID- 16992325
TI  - On the Absorption of Fluids from the Connective Tissue Spaces.

PMID- 16992327
TI  - On the Nutrition of the Frog's Heart.

PMID- 16992326
TI  - On the Relation of the Otocysts to Equilibrium Phenomena in Galasimus Pugilator
      and Platyonichus Ocellatus.

PMID- 16992328
TI  - The Action of Calcium, Strontium and Barium Salts in preventing Coagulation of
      the Blood.

PMID- 16992330
TI  - On the Structure and Degeneration of Non-Medullated Nerve Fibres.

PMID- 16992329
TI  - The Innervation of the Pelvic and adjoining Viscera: Part VI. Histological and
      Physiological Observations upon the Effects of Section of the Sacral Nerves.

PMID- 16992331
TI  - Some Experiments on the Exchange of Fluid between the Blood and Tissues.

PMID- 16992332
TI  - Observations upon the Initial Rates of Osmosis of certain Substances in Water and
      in Fluids containing Albumen.

PMID- 16992333
TI  - On the Asserted Effect of Ligature of the Portal Lymphatics on the Results of
      Intravascular Injection of Peptone.

PMID- 16992334
TI  - The Respiratory Exchange of the Lower Marine Invertebrates.

PMID- 16992335
TI  - The Innervation of the Pelvic and adjoining Viscera: Part II. The Bladder. Part
      III. The External Generative Organs. Part IV. The Internal Generative Organs.
      Part V. Position of the Nerve Cells on the Course of the Efferent Nerve Fibres.

PMID- 16992336
TI  - Contribution to the study of Lymph-formation with especial reference to the parts
      played by Osmosis and Filtration.

PMID- 16992337
TI  - Notes on Rennet and on the Coagulation of Milk.

PMID- 16992338
TI  - The Regulation of Temperature in Hybernating Animals.

PMID- 16992339
TI  - The Changes in Shape and in Position of the Heart during the Cardiac Cycle.

PMID- 16992340
TI  - On the Granular Leucocytes.

PMID- 16992341
TI  - Echo-location of bats after ablation of auditory cortex.
AB  - 1. Echo-location of blinded Yuma bats (Myotis yumanensis) was studied after
      ablation of the auditory cortex (A.C.). A task of obstacle-avoidance was given to
      the bats. Hits and misses of strands were counted, and orientation sounds emitted
      by the bats during flight were recorded.2. After bilateral ablation of A.C., two
      bats out of six failed to avoid even large obstacles such as 3.7 mm strands and
      wall. These bats emitted orientation sounds at a rate of 10-15/sec during flight,
      but did not change that rate before crossing the obstacles and crashed into them.
      In these bats, other cortical areas in addition to A.C. were probably ablated.3.
      In three bats out of six, obstacle-avoidance performance was quite normal. These
      bats avoided even 0.2 mm strands with orientation sounds, the repetition rate of
      which was systematically increased before crossing the obstacles. In two of them,
      the dorsal half of the inferior colliculus (I.C.) was bilaterally ablated in
      addition to A.C. But ability to avoid the obstacles was not impaired at all.
      Their cerebral cortices did not show the normal positive-negative diphasic
      potential change in response to tonal stimuli, although the normal diphasic
      potential change was retained in A.C. of bats which could not echo-locate as a
      result of bilateral ablation of the main nucleus of I.C. A.C. appeared to be not
      essential for echo-location.4. Unilateral ablation of A.C. and the internal
      capsule had no effect on echo-location, but bilateral ablation of them usually
      resulted in death from operational trauma.5. It was suggested that A.C. was less
      important for sound localization in bats than in cats.

PMID- 16992342
TI  - The partition of nutrients between mother and conceptuses in the pregnant rat.
AB  - 1. Diminishing the food supply to pregnant rats was associated with a subnormal
      degree of foetal loss among the larger litters, but a greatly lowered intake
      increased this foetal loss.2. Whether the food intake was lowered, normal or
      increased, the increase in conceptus weight over the last half of pregnancy could
      be related to the total maternal weight increase over this period by the formula
      y = (1/4)x + 4.5n, where n was the number of foetuses.3. With values of x below
      20 g, this no longer held, but y never fell below 4.5 (n + 1).4. It is concluded
      that Hammond's theory of the partition of nutrients is confirmed, so far as
      mother and conceptuses are concerned, in the rat.

PMID- 16992343
TI  - On the Contractility and Innervation of the Spleen.

PMID- 16992344
TI  - On the Effect of a Diastolic Load on the Diastolic Expansion of the Frog's Heart.

PMID- 16992345
TI  - Observations on the Medullated Fibres of the Sympathetic System and chiefly on
      those of the Grey Rami Communicantes.

PMID- 16992346
TI  - Reaction-time Apparatus for the Determination of Association Times, and of
      Differences between Reactions to Auditory and Visual Signals.

PMID- 16992348
TI  - Contribution to the Physiological Effects of ;Peptone' when injected into the
      Circulation.

PMID- 16992347
TI  - On the Action of Large Doses of Dilute Mineral Acids on Metabolism.

PMID- 16992349
TI  - The Chemistry of the Thyroid Gland and the Nature of its Active Constituent.

PMID- 16992351
TI  - The Detection and Estimation of Carbonic Oxide in Air.

PMID- 16992350
TI  - The Oxygen Tension of Arterial Blood.

PMID- 16992353
TI  - On Urobilin: Part I. The Unity of Urobilin.

PMID- 16992352
TI  - Notes on Creatinine.

PMID- 16992354
TI  - On the Initial Rate of Osmosis of Blood-Serum with reference to the Composition
      of "Physiological Saline Solution" in Mammals.

PMID- 16992355
TI  - Effect of Drugs on the Secretion from the Tracheal Mucous Membrane.

PMID- 16992356
TI  - Experiments on the Hearts of Mammalian and Chick-embryos, with special Reference
      to the Action of Electric Currents.

PMID- 16992357
TI  - On the Nerve Cell Connection of the Splanchnic Nerve Fibres.

PMID- 16992358
TI  - Action of Pancreatic Juice on Milk.

PMID- 16992360
TI  - The Influence of the Mesenteric Nerves on Intestinal Absorption.

PMID- 16992359
TI  - Temperature and Excitability.

PMID- 16992361
TI  - The Coagulability of the Blood of Albinos.

PMID- 16992362
TI  - A Method for the Estimation of Sugar in Blood.

PMID- 16992363
TI  - Note on the so-called Tendon Reflex.

PMID- 16992364
TI  - Sympathetic Nerve Cells and their Basophil Constituent in prolonged Activity and
      Repose.

PMID- 16992365
TI  - On the Cause of the Rise of Blood-pressure produced by Digitalis.

PMID- 16992366
TI  - A Rapid Method of separating Colloids from Crystalloids in Solutions containing
      both.

PMID- 16992368
TI  - Haemodynamics.

PMID- 16992367
TI  - The Innervation of the Pelvic and adjoining Viscera: Part VII. Anatomical
      Observations.

PMID- 16992369
TI  - On Structural Change in the Resting Nuclei of Protozoa: Part I. The Macronucleus
      of Carchesium Polypinum.

PMID- 16992371
TI  - On the Determination of the Direction and Rate of Movement of Organisms by Light.

PMID- 16992370
TI  - The Oscillations of the Auricular Tonus in the Batrachian Heart, with a Theory on
      the Function of Sarcoplasma in Muscular Tissues.

PMID- 16992372
TI  - On Reciprocal Action in the Retina as studied by means of some Rotating Discs.

PMID- 16992374
TI  - On the Mode of Absorption of Fats.

PMID- 16992373
TI  - Ingestion and Excretion of Iron in Health.

PMID- 16992375
TI  - On the Influence of Artificial Respiration and of beta Tetrahydronapthylamine on
      the Body Temperature.

PMID- 16992376
TI  - The Relation of the Respiratory Exchange of Cold-blooded Animals to Temperature:
      Part II.

PMID- 16992377
TI  - On Efferent Fibres in the Posterior Roots of the Frog.

PMID- 16992378
TI  - The Effect of a Meal on the Excretion of Nitrogen in the Urine.

PMID- 16992380
TI  - The Effect of Venous Pressure on the Pulse.

PMID- 16992379
TI  - Luminosity and Photometry.

PMID- 16992381
TI  - The Action as Poisons of Nitrites and other Physiologically Related Substances.

PMID- 16992382
TI  - Note on the Origin of the Yellow Pigment of Urine.

PMID- 16992383
TI  - On the Normal and Pathological Elimination of Carbonic Acid and of Water by the
      Skin.

PMID- 16992384
TI  - On the Question whether any Fibres of the Mammalian Dorsal (Afferent) Spinal Root
      are of Intraspinal Origin.

PMID- 16992385
TI  - A Diffusion Apparatus.

PMID- 16992386
TI  - On the Effects of Electrical Stimulation of the Mammalian Heart.

PMID- 16992387
TI  - An Inductor-Alternator for Physiological Experiments.

PMID- 16992388
TI  - The Pigments of the Decapod Crustacea.

PMID- 16992389
TI  - Studies on Reactions to Stimuli in Unicellular Organisms: I. Reactions to
      Chemical, Osmotic and Mechanical Stimuli in the Ciliate Infusoria.

PMID- 16992390
TI  - The Influence of the Force of Gravity on the Circulation: Part II. Section I. The
      Action of the Respiratory Pump. Section II. The Escape of the Heart from Vagal
      Arrest. Section III. The Mean Pressure of the Vascular System.

PMID- 16992391
TI  - The Changes in Length of Striated Muscle under Varying Loads brought about by the
      Influence of Heat.

PMID- 16992392
TI  - On the Reaction of the Intestine in Relationship to Intestinal Digestion.

PMID- 16992393
TI  - On the Chromogen and on the Active Physiological Substance of the Suprarenal
      Gland.

PMID- 16992394
TI  - The Enumeration of Blood-Platelets.

PMID- 16992395
TI  - On Intermittent Stimulation of the Retina: Part I.

PMID- 16992396
TI  - The Determination of the Coagulation-Time of Blood.

PMID- 16992397
TI  - A Comparison of the Diffusion into Serum and Absorption by the Intestine of
      Peptone and Glucose.

PMID- 16992399
TI  - Researches on the Circulation Time and on the Influences which affect it.

PMID- 16992398
TI  - An Account of Certain Phenomena of Colour Vision with Intermittent Light.

PMID- 16992400
TI  - On Halogen Derivates from Proteids.

PMID- 16992401
TI  - On the Paths of Absorption from the Peritoneal Cavity.

PMID- 16992402
TI  - On the Elimination of Water and of Carbon Dioxide from Inflamed Skin.

PMID- 16992403
TI  - On the Regeneration of Pre-Ganglionic and of Post-Ganglionic Visceral Nerve
      Fibres.

PMID- 16992404
TI  - The Absorption of Oxygen by the Lungs.

PMID- 16992405
TI  - The Vaso-Constrictor Fibres of the great Auricular Nerve in the Rabbit.

PMID- 16992407
TI  - Further Observations upon the General Physiological Effects of Extracts of the
      Suprarenal Capsules.

PMID- 16992406
TI  - The Cortical Motor Centres of the Opossum, Didelphys Virginiana.

PMID- 16992408
TI  - A Comparison of the Physiological Actions and Chemical Constitution of
      Piperidine, Coniine, and Nicotine.

PMID- 16992409
TI  - Preliminary Note on Certain Undescribed Features in the Secretory Function of the
      Uterus and Fallopian Tubes in the Human Subject and in some of the Mammalia.

PMID- 16992410
TI  - A Contribution to the Chemistry of Haemoglobin and its Immediate Derivatives.

PMID- 16992411
TI  - The Influence of Pathological Conditions on Active Absorption of Oxygen by the
      Lungs.

PMID- 16992412
TI  - Decerebrate Rigidity, and Reflex Coordination of Movements.

PMID- 16992414
TI  - On the Origin, Course and Cell-connections of the Viscero-motor Nerves of the
      Small Intestine.

PMID- 16992413
TI  - The Physiology of the Salmon in Fresh Water.

PMID- 16992415
TI  - An Intestinal Plethysmograph.

PMID- 16992417
TI  - On Hepatic Glycogenesis.

PMID- 16992416
TI  - The Effect of Resistance to Secretion upon the Percentage of Salts in Saliva, and
      upon the Work done by the Gland.

PMID- 16992418
TI  - The Precipitation of Carbohydrates by Neutral Salts.

PMID- 16992419
TI  - Hydrolysis of Glycogen.

PMID- 16992420
TI  - On Intermittent Stimulation of the Retina: Part II.

PMID- 16992421
TI  - On Urobilin: Part II. The Percentage Composition of Urobilin.

PMID- 16992422
TI  - Some Improved Methods of Gas Analysis.

PMID- 16992423
TI  - Contributions to the Physiology of Unstriated Muscular Tissue: Part IV. The
      Action of Electrical Stimuli upon the OEsophagus of Aplysia Depilans, and Aplysia
      Limacina.

PMID- 16992424
TI  - On the Antagonistic Action of Digitalis and the Members of the Nitrite Group.

PMID- 16992425
TI  - On the General Physiological Effects of Extracts of the Suprarenal Capsules.

PMID- 16992426
TI  - A further Study of Hepatic Glycogenesis.

PMID- 16992427
TI  - The Photometry of Coloured Paper.

PMID- 16992428
TI  - The Formation of Uric Acid in Man, and the Influence of Diet on its Daily Output.

PMID- 16992429
TI  - The Pharmacology of the Chlor-Hydrins: a Contribution to the Study of the
      Relation between Chemical Constitution and Physiological Action.

PMID- 16992430
TI  - Experimental Observations on the crossed Adductor Jerk.

PMID- 16992431
TI  - On the Influence of Muscular Exercise, Sweating, and Massage, on the Metabolism.

PMID- 16992432
TI  - A new Method of distinguishing between Organic and Inorganic Compounds of Iron.

PMID- 16992433
TI  - A Contribution to the Study of Geotaxis in the Higher Animals.

PMID- 16992434
TI  - Dynamic properties of inferior rectus muscle of the rat.
AB  - 1. Isometric responses of rat inferior rectus muscle to indirect and direct
      stimulation were compared, and conditions were found for selective direct
      stimulation of twitch fibres in vitro.2. Most of the twitch fibres were
      qualitatively ;fast'.3. The influence of length on isometric contractions and the
      relation between relative load and speed of sarcomere shortening of fast-twitch
      fibres were determined.4. The isometric twitch contraction and half-relaxation
      times of fast-twitch inferior rectus fibres were only about one half of those of
      rat extensor digitorum longus fibres in the same conditions, whereas the force:
      velocity properties of these two fibre groups were virtually the same. These
      results show that the relation between intrinsic speed of shortening and duration
      of the active state of the contractile material is not the same for rat
      extraocular and hind-limb muscles.

PMID- 16992435
TI  - The regulation of corneal hydration by a salt pump requiring the presence of
      sodium and bicarbonate ions.
AB  - 1. The use of polyacrylamide gel salt bridges enables trans-membrane potentials
      to be measured to an accuracy of 20 muV over long periods.2. The technique is
      applied to measure electrical potentials across corneal endothelia of rabbits.3.
      In de-epithelialized corneas which translocate water, a spontaneous potential of
      550 muV is found across the endothelium (tissue resistance 20 Omega cm(2)).4.
      This electrical potential (and water translocation) is reduced to zero when
      sodium is absent from the Ringer, and by about 80% when bicarbonate ions are
      absent. Removal of chloride has no such effect.5. Under a variety of conditions,
      the potential correlates with the observed translocation of fluid across corneal
      endothelium. The translocated fluid is shown to be isotonic with sodium in the
      Ringer and therefore the potential correlates with ;active' sodium transport.6.
      The potential and water translocation are abolished in the presence of ouabain at
      concentrations greater than 10(-5)M.7. The potential (lens-side negative) is of
      the wrong polarity to explain the net sodium transport (into the lens-side) by a
      sodium ion ;pump'.8. The current does not equal the net sodium flux under short
      circuit conditions. They differ in magnitude and polarity.9. A model is proposed
      where the endothelium ;pumps' salt out of the corneal stroma into the aqueous
      humour.10. Flux equations are derived for a condition where the membrane (corneal
      endothelium) separates an ion exchanger (corneal stroma) from free solution
      (aqueous humour), where the usual relationship for free-free solutions Deltapi =
      c(s)Deltamu(s) does not apply.11. The model is of use only when the stroma is
      well stirred. It may be used in whole corneas retaining their epithelium but it
      may not be used in de-epithelialized corneas.12. The model predicts that the
      presence of an ;active' salt flux out across the endothelium would create passive
      water and salt fluxes. The passive water flux would also travel out of the stroma
      across the endothelium; the passive salt flux would travel, in the opposite
      direction, into the stroma across the endothelium.13. The kinetics of the passive
      water efflux, as a swollen cornea reverts to physiological hydration (the
      temperature reversal phenomenon) are predicted extremely well if the ;active'
      salt flux is chosen at 3.3 x 10(-7) m-mole. cm(-2) sec(-1).14. The value of the
      active salt flux which cannot be measured directly is extrapolated to be somewhat
      greater than 2.8 x 10(-7) m-moles. cm(-2) sec(-1); in good agreement with that
      required by the model to explain the temperature reversal phenomenon.15. The
      model is further used to calculate the salt concentration difference across the
      endothelium (which drives salt passively into the stroma) at various stromal
      hydrations.16. When an appropriate salt concentration is applied across the
      endothelium of de-epithelialized cornea, it generates a potential of the same
      polarity and similar magnitude to that found across the endothelium of
      equilibrated whole cornea. The endothelium acts like a cation exchange
      membrane.17. Additionally the calculated salt concentration difference across the
      endothelium correlates well with the measured transendothelial potentials in
      whole cornea as the corneal hydration varies.18. It is concluded that the model
      of an endothelial neutral salt ;pump' regulating corneal hydration is self
      consistent. The spontaneous potential found across the endothelium could be
      caused by the consequential passive flux of salt in the opposite direction.

PMID- 16992436
TI  - Two types of neurones in the myenteric plexus of duodenum in the guinea-pig.
AB  - 1. Intracellular recordings have been made from neurones lying in the myenteric
      plexus of guinea-pig duodenum; some aspects of their membrane properties have
      been studied by passing current through the intracellular electrode while
      recording changes in membrane potential.2. The current-voltage relationship was
      linear for small changes in membrane potential, input resistances ranging from
      125 to 250 MOmega. Larger hyperpolarizing currents (causing changes of 20-40 mV)
      caused the input resistance to fall.3. Depolarizing currents of 1 to 10 x 10(-10)
      A initiated action potentials with amplitudes of up to 95 mV.4. Two types of cell
      were distinguished when an action potential was initiated. In one group the
      action potential and undershoot had a form similar to that recorded from other
      mammalian ganglia. In the second group an action potential was followed by both
      an undershoot and a prolonged afterhyperpolarization which was associated with a
      decrease in cell resistance.5. The two groups of cells were further distinguished
      by their responses to transmural stimulation. Only those cells which did not show
      an afterhyperpolarization could be shown to receive a synaptic input.6. The
      mechanism by which each cell type generates an action potential was different.
      The action potentials recorded from cells which had a detectable synaptic input
      were abolished by tetrodotoxin. In contrast, those recorded from the other type
      of cells persisted in the presence of tetrodotoxin. Preliminary experiments
      suggest that during an action potential these cells become permeable to both
      sodium and calcium ions.7. Abolition of the calcium component of the action
      potential in cells which generated an afterhyperpolarization abolished this
      latter potential.8. The role of these two groups of cells is discussed.

PMID- 16992437
TI  - The intervals between miniature end-plate potentials in the frog are unlikely to
      be independently or exponentially distributed.
AB  - 1. It has been suggested that spontaneous quantal release of transmitter at the
      neuromuscular junction is a Poisson process. One logical argument against
      accepting the Poisson hypothesis is that so far relatively few intervals between
      miniature end-plate potentials (min.e.p.p.s) have been studied in any single
      experiment. Release is known to occur from many sites on the nerve terminal, so
      many intervals must be studied before drawing any conclusions about the timing of
      release from the individual sites. Moreover, the statistical methods that have
      been used are relatively insensitive to deviations from Poisson predictions.2.
      The Poisson hypothesis is evaluated with respect to three major criteria:(a) The
      fit to the exponential distribution is analysed by five goodness of fit tests
      which were applied to eleven sets of data, showing that it is unlikely that the
      data sets were generated by an exponential distribution.(b) The independence of
      intervals is assessed in two ways. First, the autocorrelogram of intervals is
      constructed. This shows an excess of significant positive correlations beyond the
      5% limits of the Poisson expectation. Secondly, the unsmoothed power spectrum is
      calculated, and compared to the Poisson prediction by means of the modified mean
      test. Again, most sets deviate significantly from the Poisson expectation. It is
      unlikely that the intervals are independent.(c) The possibility of simultaneous
      occurrences is evaluated by construction of the amplitude histogram of
      min.e.p.p.s. In all sets the Poisson prediction for the frequency of multiples of
      the unit height was exceeded by the empirical data sets. The over-all conclusion
      is that the process which generates spontaneous releases is unlikely to be
      Poisson.

PMID- 16992438
TI  - The stochastic properties of spontaneous quantal release of transmitter at the
      frog neuromuscular junction.
AB  - 1. Earlier results showed that it is unlikely that spontaneous quantal release of
      transmitter at the frog neuromuscular junction is produced by a Poisson
      process.2. Data sets were tested, by using the u statistic, to see whether if
      they are assumed to be generated by a Poisson process, the mean interval is
      changing monotonically with time. By this critieria, some of the data sets are
      stationary, others are not.3. A variety of mathematical transforms are employed
      on empirical data sets to characterize the properties of the spontaneous quantal
      release.(a) The intensity function, which calculates the frequency distribution
      of all possible combinations of intervals, shows an excess of short intervals,
      without any sign of periodicity.(b) The variance-time curve, which estimates the
      accumulated variance of the series as a function of time into the series, lies
      significantly above the Poisson prediction.(c) The power spectrum, whether
      calculated on the intervals or on the number of intervals in time bins, deviates
      significantly from the Poisson prediction at the low frequencies.(d) The ln
      survivor curve has two phases: a concave section for the short intervals, and a
      roughly linear section for the intervals of greater length.These transforms
      indicate that the min.e.p.p.s are clustered.4. A series of models for spontaneous
      quantal release were considered.(a) A Poisson model. Rejected because of
      consistent failure to fit the data.(b) A periodic model. Rejected because the
      intervals should be ordered rather than clustered.(c) A time-dependent model, in
      which quantal release is governed by a Poisson process with a mean interval that
      is oscillating in time. This model will generate clustering; by the transforms
      the model can be shown to closely fit the data. However, an autocorrelation of
      min.e.p.p. amplitudes shows that there is a relationship between the amplitudes
      and their position in the series. This is not predicted by the time-dependent
      oscillating model.(d) A branching Poisson model, in which a primary release,
      generated by a Poisson process, is likely to be followed by one or more
      subsidiary releases from the same site. The parameters of the branching model can
      be determined from ln-survivor curves. Theoretical curves, created with these
      parameters, give power spectra, variance-time curves, and ln-survivor curves that
      strongly resemble those calculated from the data. The model also predicts a
      significant autocorrelation of amplitudes.5. Min.e.p.p.s recorded with an
      extracellular electrode also fit well to a branching Poisson model.6. The effects
      of raised [Ca(2+)](o) on the intervals between min.e.p.p.s were studied. In our
      experiments the change in extracellular solution did not produce any notable
      change in release statistics.7. The effects of elevated [K(+)](o) on the
      intervals between spontaneous releases were studied. Depolarization of the nerve
      terminal increases the frequency of primary releases and decreases the chance of
      having subsidiary releases.8. Possible physical mechanisms by which quantal
      release of transmitter from a nerve terminal would fit a branching Poisson model
      are described.

PMID- 16992439
TI  - Stochastic properties of spontaneous transmitter release at the crayfish
      neuromuscular junction.
AB  - 1. Miniature excitatory junctional potentials (min.e.j.p.s) were recorded with an
      intracellular electrode from the adductor muscle of the dactyl of the first or
      second walking leg of the crayfish, Orconectes virilis.2. The intervals between
      the min.e.j.p.s were compared to the exponential prediction by five goodness of
      fit tests. The results indicate that the intervals are not exponentially
      distributed.3. The autocorrelogram of intervals shows that the intervals are
      unlikely to be independent.4. A stochastic analysis that includes the power
      spectrum of intervals, the variance-time curve, and the ln-survivor curve suggest
      that there is a clustering of min.e.j.p.s. The results are similar to those on
      the frog neuromuscular junction.5. An autocorrelogram of the min.e.j.p.
      amplitudes suggests that sizes are not independently distributed.6. These
      results, which are similar to those previously reported from the frog
      neuromuscular junction, support the use of the branching Poisson process as a
      theoretical model for the stochastic properties of spontaneous quantal release of
      transmitter.

PMID- 16992440
TI  - Does the vestibular apparatus play a role in the development of the visual
      system?
AB  - 1. The receptive field properties of visual cortical neurones were investigated
      in kittens that had been subjected to either unilateral or bilateral
      labyrinthectomy shortly after birth.2. Two kittens were reared in a normal visual
      environment. Another two were reared in the dark with recurrent exposures to
      vertically oriented black and white stripes, which in normal kittens is known to
      bias the distribution of receptive field orientations.3. For both normally reared
      and stripe-reared labyrinthectomized kittens, no differences were detected in
      cell types, preferred orientations, binocularity, columnar organization, or any
      other neuronal properties, compared with similarly reared intact kittens.4. The
      failure to detect deficits in visual development after labyrinthectomy is
      discussed in relation to other reports of vestibular influences on the visual
      system of the adult cat.

PMID- 16992441
TI  - The kinetics of the reaction of carbon monoxide with fully oxygenated haemoglobin
      in solution and erythrocytes.
AB  - 1. Spectrophotometric measurements, using a rapid mixing and stopped flow
      technique, have been made of the rate at which CO displaces O(2) from its
      combination with haemoglobin.2. In haemoglobin solutions, buffered at pH 7.2 and
      9.1, the reaction proceeds by a unimolecular dissociation as proposed by Gibson &
      Roughton (1955). In a Ringer-Locke solution, equilibrated with a P(CO(2) ) of 3
      cmHg and at pH 7.4, the reaction of HbO(2) with CO is a two-stage process, with a
      transition from one form of Hb(4)O(6) to another.3. An investigation of the
      reaction between CO and HbO(2) in erythrocytes, suspended in Ringer-Locke
      solution, indicates that the rate is determined by the chemical reaction and this
      also is a two-stage process.4. The transition is probably associated with the
      reaction of CO(2) with Hb(4)O(6), following the dissociation from fully saturated
      oxyhaemoglobin of an oxygen molecule. It alters the relative velocity constants
      of the reactions of O(2) and CO with Hb(4)O(6) by 100:1.5. The implications of
      these proposals of the equilibria of haemoglobin with CO and O(2) are discussed.
      The difference between the sigmoid equilibria curves at high HbO(2) and HbCO
      values can be explained as due to the different reaction pathways.

PMID- 16992442
TI  - The effect of antidiuretic hormone on human sweating.
AB  - 1. Changes in insensible perspiration and sweating were followed in normal
      subjects by continuously monitoring total body weight loss in environmental
      temperatures of 18, 29 and 37 degrees C.2. Pharmacological doses of ADH had no
      effect on cutaneous water loss at 18 degrees C.3. Pharmacological doses of ADH
      are capable of increasing the rate of cutaneous water loss in human subjects who
      are close to or above the thermal sweating threshold.4. Physiological doses of
      ADH had no effect on cutaneous water loss in either cool or hot environments.5.
      At normal rates of secretion in the body, ADH probably does not influence human
      sweat secretion.

PMID- 16992443
TI  - Anode break excitation in denervated rat skeletal muscle fibres.
AB  - 1. Anodal break action potentials were found to be a feature of denervated rat
      skeletal muscle fibres.2. Depolarized innervated fibres failed to respond to
      anodal break stimulation in the same way as denervated fibres.3. The critical
      level for action potential generation is related to membrane polarization in
      denervated fibres but not in innervated fibres. This relationship is inhibited by
      the I.P. administration of actinomycin D, which also prevents the onset of anodal
      break action potentials in 3-day denervated fibres.

PMID- 16992445
TI  - Synaptic connexions of two symmetrically placed giant serotonin-containing
      neurones.
AB  - 1. Each giant serotonin cell in Helix pomatia makes synaptic connexions with
      three non-amine-containing neurones: the anterior, middle and posterior buccal
      cells.2. Individual e.p.s.p.s, of 500-600 msec duration, were observed in both
      left and right middle cells following each evoked giant serotonin cell action
      potential. They were facilitated with repetitive stimulation of the giant
      serotonin cells and summed to give rise to an action potential. The membrane
      resistance of the middle cells was reduced when the giant serotonin cells were
      stimulated to fire rapidly. Evidence is presented which suggests that the link
      between each giant serotonin cell and each middle cell is monosynaptic.3.
      Iontophoretically applied serotonin produced a depolarizing potential change in
      the middle cell perikaryon; the response rapidly desensitized on repetitive
      application.4. Morphine abolished reversibly the middle cell serotonin potential
      and antagonized transmission from the giant serotonin cells to the middle cells.
      Lowering the Na concentration of the medium reversibly diminished the size of the
      serotonin potential and the giant serotonin cell elicited e.p.s.p.s in the middle
      cells.5. Reserpine, which depletes serotonin in the giant serotonin cell,
      impaired transmission from these cells to the middle cells.6. The results suggest
      that serotonin is the synaptic transmitter released from the giant serotonin
      cells on to the middle cells and that this system is a suitable model for further
      analysis of the neuronal role of serotonin.

PMID- 16992444
TI  - The influence of the splanchnic nerves on the external secretion, blood flow and
      electrical conductance of the cat pancreas.
AB  - 1. Electrical stimulation of the cut peripheral end of the splanchnic nerves
      results in a biphasic change in electrical conductance measured across the tail
      of the pancreas. A phase of decreased conductance is followed by a more prolonged
      phase of increased conductance.2. Simultaneous measurements of pancreatic blood
      flow indicate that the phase of decreased conductance occurs as a result of
      vasoconstriction, whilst the phase of increased conductance is due to
      vasodilatation.3. The initial phase of decreased conductance and vasoconstriction
      is abolished by alpha-receptor blocking agents such as phenoxybenzamine and the
      phase of increased conductance blocked by beta-receptor blocking agents such as
      pronethalol.4. Short periods of electrical stimulation applied to the splanchnic
      nerves result in a secretion of amylase and a reduction in the volume rate of
      secretion.5. When the vasoconstrictor response was abolished by phenoxybenzamine,
      nerve stimulation still reduced the rate of secretion, suggesting that the
      inhibitory effect is in part due to a direct action of the secretory cells.6.
      After bretylium tosylate, splanchnic nerve stimulation no longer produced
      vasomotor changes in the pancreas and the inhibitory effect on the volume
      response was converted to one of augmentation, but the secretion of enzymes was
      unaffected.7. The secretion of amylase on splanchnic stimulation was abolished by
      intravenous injection of atropine, suggesting that a cholinergic mechanism is
      involved.8. Noradrenaline did not mobilize pancreatic enzymes.

PMID- 16992446
TI  - Levels of prostaglandins in human endometrium during the normal menstrual cycle.
AB  - The levels of prostaglandins in the human endometrium throughout the normal
      menstrual cycle were measured by bioassay. The identity of prostaglandin
      F(2alpha) and prostaglandin E(2) in endometrial tissue extracts was established
      by combined gas chromatography/mass spectrometry.The levels of prostaglandin
      F(2alpha) and prostaglandin E(2) are low during the proliferative phase of the
      cycle (10-25 ng/100 mg tissue). Prostaglandin F(2alpha) rises significantly
      during the luteal phase to levels of 65-75 ng/100 mg of tissue. Prostaglandin
      E(2) levels are similar to prostaglandin F(2alpha) levels in the proliferative
      phase but remain lower during the luteal phase. The prostaglandin E(2) level is
      highest at menstruation (52 ng/100 mg tissue). The implications of these findings
      are discussed in relation to the menstrual process and to the steroid hormonal
      changes during the cycle.

PMID- 16992447
TI  - Release of endogenous noradrenaline from an isolated elastic artery.
AB  - 1. The overflow of noradrenaline following field stimulation of vasoconstrictor
      nerves has been studied in isolated preparations of the guineapig thoracic
      aorta.2. Stimulation with trains of 3000 pulses at 5 and 25 pulses.s(-1) resulted
      in mean overflows of 0.15 and 0.17 (ng.g(-1)).pulse(-1) respectively.3. These
      overflows were not affected by pre-treatment of the aortae with the inhibitor of
      neuronal amine re-uptake desmethylimipramine (10(-5)M) or with the inhibitors of
      extraneuronal amine uptake metanephrine (5 x 10(-4)M) or desoxycorticosterone
      (2.5 x 10(-5)M).4. In contrast, inhibition of monoamine oxidase and catechol-O
      methyl transferase with pargyline (1 x 10(-4)M) and tropolone (2.5 x 10(-4)M)
      caused the mean overflows to be increased to 0.27 and 0.31 (ng.g(-1)).pulse(-1)
      in response to stimulation at 5 and 25 pulses.s(-1) respectively. Inhibition of
      either enzyme alone had little effect.5. It is concluded that in the guinea-pig
      aorta nervously released noradrenaline is inactivated primarily by enzymic
      metabolism, while neural re-uptake is insignificant. This situation is the
      reverse of that existing in the uterine artery of the same species.6.
      Phenoxybenzamine (10(-5)M) also caused pronounced increases in overflow at both
      high and low frequencies of stimulation. This could be due to an effect of
      phenoxybenzamine on release of noradrenaline or on some tissue uptake mechanism
      distinct from the normal neuronal and extraneuronal pathways.7. Calculations
      based on the overflow at 5 pulses.s(-1) following total enzyme inhibition
      indicated that a single stimulating pulse liberated 2.1 x 10(-4) of the total
      transmitter store.

PMID- 16992448
TI  - The effect of lowering the 5-hydroxytryptamine content of the rat spinal cord on
      analgesia produced by morphine.
AB  - 1. Injection of 5,6-dihydroxytryptamine (5,6-DHT, 50 mug) into a lateral cerebral
      ventricle of male rats lowered the 5-hydroxytryptamine (5-HT) content of the
      lumbar cord to 12.8% and reduced the analgesic effect of low doses of morphine
      (0.64-1.63 mg/kg), tested by exerting pressure on the foot; after doses of
      morphine of 1.33-1.63 mg/kg, the analgesic response was reduced or abolished in
      33% of the rats, and after 0.64 mg/kg, 58% of the animals failed to respond
      normally.2. Two days after an I.P. injection of p-chlorophenylalanine (pCPA, 320
      mg/kg), the loss of analgesic potency of morphine was more pronounced than after
      intraventricular 5,6-HDT. The 5-HT content was lowered to about 8% in the lumbar
      cord, and to 20% or less in pons and medulla.3. The experiments show that
      interference with the descending tryptaminergic axons innervating the cord is by
      itself sufficient to reduce analgesia due to morphine, but they do not exclude
      the possibility that other tryptaminergic neurones take part in the effect of
      pCPA. The contribution to the analgesic effect of morphine made by the
      interaction of tryptaminergic axons with the interneurones ;gating' the afferent
      impulses in the posterior columns is discussed.

PMID- 16992449
TI  - Experiments upon the Osmotic Properties of the Living Frog's Muscle.

PMID- 16992451
TI  - The Hydrolysis of Proteids.

PMID- 16992450
TI  - On the Sequence of Certain Changes in the Urine produced by Exercise and by
      Turkish Baths.

PMID- 16992452
TI  - Further Observations on the Chemistry and Action of the Thyroid Gland.

PMID- 16992453
TI  - On the Minute Anatomy of the Neuromuscular Spindles of the Cat, and on their
      Physiological Significance.

PMID- 16992454
TI  - Absorption of Fat after Ligature of the Biliary and Pancreatic Ducts.

PMID- 16992455
TI  - The Metabolism of the Nucleins under Physiological and Pathological Conditions:
      Part I.

PMID- 16992457
TI  - On the Relation of Uric Acid Excretion to Diet.

PMID- 16992456
TI  - On the Union of Cranial Autonomic (Visceral) Fibres with the Nerve Cells of the
      Superior Cervical Ganglion.

PMID- 16992458
TI  - On a new Proteid Reaction.

PMID- 16992459
TI  - The Resistance to the Blood-flow.

PMID- 16992460
TI  - On the alleged Sensory Functions of the Motor Cortex Cerebri.

PMID- 16992461
TI  - The Relation of the Degree of Acidity of the Urine and the Percentage of Uric
      Acid therein contained to the Precipitation of the latter in the form of Uric
      Acid Gravel.

PMID- 16992462
TI  - The Electrical Response to Stimulation of Muscle: Part II. The Monophasic and
      Diphasic Variation of the Sartorius.

PMID- 16992463
TI  - Further Observations upon the Action of the Oxyphil and Hyaline Cells of Frog's
      Lymph upon Bacilli.

PMID- 16992464
TI  - The Action of Arsenic on the Bone-Marrow and Blood.

PMID- 16992465
TI  - Cortical Localisation in Ornithorhynchus.

PMID- 16992466
TI  - Observations upon the Deep and Surface Temperature of the Human Body.

PMID- 16992468
TI  - The results following partial Nephrectomy and the influence of the Kidney on
      Metabolism.

PMID- 16992467
TI  - On Inhibitory Fibres in the Vagus for the end of the OEsophagus and the Stomach.

PMID- 16992469
TI  - On the Quantitive Analysis of Potassium and Sodium in Urine.

PMID- 16992470
TI  - The Physiological Action of certain Mineral Waters and Baths on the Blood, and on
      the excretion of Urea and Uric Acid: with a note on the Quantitative Relationship
      between Uric Acid and Leucocytes.

PMID- 16992471
TI  - Alkaptonuria: a simple method for the extraction of Homogentisinic Acid from the
      Urine.

PMID- 16992472
TI  - Upon the Production of Rapid Voluntary Movements.

PMID- 16992473
TI  - The Survival, Respiration of Muscle.

PMID- 16992474
TI  - Electromotive Changes in the Phrenic Nerve. A Method of investigating the Action
      of the Respiratory Centre.

PMID- 16992475
TI  - On the Structural Alterations observed in Nerve Cells.

PMID- 16992477
TI  - The pigments of Aplysia Punctata.

PMID- 16992476
TI  - Observations on the Crystallization of Animal Proteids.

PMID- 16992478
TI  - Further observations on the elimination of water and carbon dioxide by the skin.

PMID- 16992479
TI  - The pathological effects due to increase of oxygen tension in the air breathed.

PMID- 16992480
TI  - Some observations on the mode of conversion of glycogen to glucose in the liver.

PMID- 16992481
TI  - On the excretion of phosphorus and nitrogen in leukhaemia.

PMID- 16992483
TI  - On the vaso-motor nerves of the small intestines.

PMID- 16992482
TI  - On plain muscle.

PMID- 16992484
TI  - Note on the muscular response to two stimuli of the sciatic nerve (frog).

PMID- 16992485
TI  - Some remarks on the excretion of uric acid and its relation to solubility.

PMID- 16992486
TI  - On the structure of cell protoplasm: Part I. The Structure produced in a Cell by
      Fixative and Post-mortem change. The Structure of Colloidal matter and the
      Mechanism of Setting and of Coagulation.

PMID- 16992487
TI  - The movements and innervation of the small intestine.

PMID- 16992489
TI  - The relative volume or weight of corpuscles and plasma in blood.

PMID- 16992488
TI  - On the modifications of the metabolism produced by the administration of
      diptheria toxine.

PMID- 16992490
TI  - The physiological effects of "peptone" when injected into the circulation: Part
      II. The influence of purified peptone, of antipeptone, and of proteoses, on blood
      coagulation and on the vaso-motor system.

PMID- 16992491
TI  - The physiological effects of "peptone" when injected into the circulation: Part
      III. The local vascular influences of peptone and proteoses: effects on the
      intestinal and renal districts.

PMID- 16992492
TI  - The electrical response of nerve to two stimuli.

PMID- 16992493
TI  - The Proteids of Muscle.

PMID- 16992494
TI  - The effect on the molecular concentration and electrical conductivity of muscle
      extracts of removal of the proteids.

PMID- 16992495
TI  - Further observations on the structural alterations observed in nerve cells.

PMID- 16992496
TI  - An enquiry into the effects on the blood and urine of the intravenous and
      subcutaneous injection of various carbohydrates standing in relation to animal
      life.

PMID- 16992497
TI  - The behaviour of the haemoglobin and electrolytes of the coloured corpuscles when
      blood is laked.

PMID- 16992498
TI  - Heat rigor in cold-blooded animals.

PMID- 16992499
TI  - On the coagulation of proteid by electricity.

PMID- 16992501
TI  - The glomerular functions of the kidney.

PMID- 16992500
TI  - The relation between the internal temperature and the respiratory movements of
      hibernating animals.

PMID- 16992502
TI  - The effects of extracellular pH and buffer concentration on the efflux of lactate
      from frog sartorius muscle.
AB  - 1. The rate of efflux of lactate from isolated frog sartorius muscles is measured
      with a superfusion technique. Efflux curves are followed after raising the
      internal lactate level of the muscles by repetitive electrical stimulation over a
      200 sec period.2. With an external pH of 7.0 or below the measured efflux rates
      following stimulation reach 100-150 n-mole/g.min. Increasing the pH of the
      superfusion fluid to 8.0 results in a two or threefold increase in the peak
      efflux rate. The effect is independent of the buffer system used and occurs
      fairly rapidly when the pH of the superfusion fluid is changed. This suggests
      that the effect of pH on lactate efflux is extracellular.3. The increase in
      efflux rate due to an increase in pH is dependent on buffer concentration. This
      fact together with measurements of surface pH changes in muscles following arrest
      of superfusion indicates that a pH gradient exists through the muscle thickness
      during lactate efflux.4. The low lactate efflux rate seen at a low buffer
      concentration (1 mM) is reduced to an even lower level by depolarization with
      potassium sulphate suggesting a membrane potential dependent component. At pH 8.0
      with a high buffer concentration (25 mM) potassium sulphate only reduces efflux
      rate slightly.The observations are interpreted as indicating that a fraction of
      lactate lost is in the form of undissociated acid and that this fraction
      increases with increasing external pH.5. Conditions which favour loss of hydrogen
      ions and lactate from muscle are also associated with improved recovery of twitch
      tension.

PMID- 16992503
TI  - Facilitated transport of prostaglandins across the blood-cerebrospinal fluid and
      blood-brain barriers.
AB  - 1. Ventriculo-cisternal perfusions were performed on rabbits with artificial
      cerebrospinal fluid containing blue dextran and tritium-labelled prostaglandin
      F(2alpha) ([(3)H]PGF(2alpha)). In order to study the nature of prostaglandin (PG)
      transfer across the blood-brain barrier, high concentrations of PGF(2alpha) or
      potential PG transport inhibitors were added to the perfusion fluid after the
      normal rate of [(3)H]PGF(2alpha) clearance was established.2. The
      [(3)H]PGF(2alpha) clearance was inhibited by 10(-6) to 10(-3)M PGF(2alpha),
      PGF(2beta), probenecid, iodipamide or bromcresol green but not by perchlorate.3.
      The (3)H content of the brain, relative to the (3)H-activity in the ventricular
      system, was also increased by high concentrations of PGF(2alpha), iodipamide or
      bromcresol green.4. It is concluded that the removal of PGs from the
      extracellular fluids of the brain is mediated by saturable, facilitated transport
      processes across both the choroidal and extrachoroidal regions of the blood-brain
      barrier system. In the case of the mammalian brain, such facilitated PG transport
      appears to be the primary mechanism for the termination of the action of these
      potent, endogenously produced autacoids.

PMID- 16992504
TI  - The time-dependent and dose-dependent effects of caffeine on the contraction of
      the ferret heart.
AB  - 1. Trabeculae isolated from ferret heart and from other mammalian hearts have
      been mounted in a way that enables the tension generated to be measured while the
      composition of the bathing fluid is rapidly altered.2. Application of caffeine to
      these trabeculae initiates a rapid transient contracture and depresses the
      strength of regularly evoked heart beats.3. The strength of the contractures, the
      rate of tension development and the rate of spontaneous relaxation are all
      increased by raising the concentration of the applied caffeine.4. The strength of
      the caffeine contracture is relatively unaffected by changes in the bathing
      Na(+), K(+) or Ca(2+) concentrations, but is reduced by exposure to the free-base
      form of local anaesthetics.5. Lowering of the temperature has complex effects on
      the amplitude of the caffeine contracture due to the differing temperature
      sensitivities of the contraction and spontaneous relaxation.6. Following a
      caffeine contracture, a period of perfusion by caffeinefree solution is required
      before a full-sized contracture can be evoked by the re-application of caffeine.
      This re-priming of the caffeine contracture has a sigmoidal time course that can
      be fitted by a two compartment model. The rate constants of the filling of each
      of the compartments can be obtained analytically, and are found to be increased
      by raising the extracellular calcium concentration, [Ca](o), by stimulating the
      preparation or by raising the temperature. Reducing the [Na](o) or raising the
      [K](o) has little effect on these processes.7. The presence of traces of caffeine
      in the perfusing fluid between the conditioning and test challenges with the
      caffeine contracture solution reduces the extent of the re-priming without much
      affecting its rate.8. The behaviour of several model systems have been compared
      with that of the heart with the aid of an analogue computer. A four compartment
      closed system has been found to simulate the results presented in this paper.9.
      It appears that caffeine has its effects by acting to increase the rate of
      release of activator calcium from one part of a non-homogeneous intracellular
      relaxing system present within the mammalian heart, which is likely to be the
      sarcoplasmic reticulum.

PMID- 16992505
TI  - A mechanism for spike frequency adaptation.
AB  - 1. Spike frequency adaptation was studied in large neurones of the marine
      molluscs Archidoris montereyensis and Anisodoris nobilis. These cells respond to
      a current step with a rapid rise in spike frequency followed by a gradual decline
      to a new steady level.2. An exponentially declining current, I(s), was measured
      when the cell was voltage clamped following an adapting spike train. The initial
      amplitude of this current depended on the preceding number of spikes and on the
      voltage to which the cell was clamped. A reversal potential (V(s)) for this
      current was obtained by clamping to various potentials following a spike train.
      The time constant (tau(s)) of decay of the current was dependent upon the
      clamping potential.3. Clamping the membrane potential to a constant test level
      from various initial levels initiates an exponentially decaying current of
      similar time constant. The voltage dependence of the steady-state conductance
      (g(s)a(s)(V, infinity)) associated with this current was determined using this
      technique.4. Equations for neural repetitive firing (Connor & Stevens, 1971c)
      were modified by the addition of a term describing these slow membrane currents:
      [Formula: see text]. The solution to the modified equation was in good agreement
      with the spike frequency adaptation observed in these cells.

PMID- 16992506
TI  - Voltage gradients across the receptor layer of the isolated rat retina.
AB  - 1. The electroretinogram (e.r.g.) of the isolated rat retina has been
      investigated by recording potential differences developed between two
      micropipettes.2. In the uniformly illuminated receptor layer, voltage gradients
      at 90 degrees to the long axes of the receptors are negligible in comparison with
      the radial voltage gradients.3. When all transsynaptic neural activity has been
      abolished, the photoresponse recorded across the receptor layer is very different
      from the photoresponse recorded across the inner retinal layer.4. The
      photoresponse developed across the inner retinal layers, slow P III, develops
      slowly and the peak voltage is approximately proportional to log. flash energy.5.
      The photovoltage across the receptor layer rises rapidly to its peak, before a
      significant fraction of slow P III has developed.6. The faster photovoltage
      (receptor potential) increases with flash intensity according to the hyperbolic
      function characteristic of photo-receptors.7. The faster photovoltage can be
      split into two components. Between the tips of the outer limbs and the bases of
      the inner limbs, it has a simple wave form. In the region between the bases of
      the inner limbs and the receptor synapses, there is an additional peak (nose) to
      the photovoltage.8. In the scleral portion of the receptor layer, the
      photovoltage approximately equals the dark voltage. In the remaining, vitreal
      portion of the receptor layer the photovoltage exceeds the dark voltage.9.
      Photocurrent divergence has been measured and the results indicate that the
      source of photocurrent extends further vitreally than the base of the outer
      limb.10. The results suggest that the photoresponse generated in the outer limb
      is modified by an active process which occurs in portions of the rods which are
      nearer the synapse.

PMID- 16992507
TI  - Short-term adaptive changes in the human vestibulo-ocular reflex arc.
AB  - 1. Two sets of experiments have examined the vestibulo-ocular response (VOR) to
      repeated sinusoidal rotation (A) in the dark and (B) after attempting visual
      tracking of a mirror-reversed image of the visual surround.2. In both A and B a
      horizontal sinusoidal rotational stimulus of 1/6 Hz and 60 degrees /sec angular
      velocity amplitude was employed, specifically chosen to lie within the presumed
      range of natural stimulation of the semicircular canals.3. In A each of seven
      subjects underwent ten 2-min runs of the standard stimulus in the dark on each of
      three consecutive days, with 3-min rest periods between runs. Using d.c. electro
      oculography (EOG) the VOR gain was measured throughout as eye velocity/head
      velocity. Mental arousal was maintained by competitive mental arithmetic.
      Constancy of EOG gain was assured by 50 min dark adaptation before
      experimentation.4. The results of A showed no consistent change of VOR gain over
      the three times scales of a run, a day and the 3-day experiment.5. In B the same
      subjects underwent a similar pattern of vestibular stimulation, but during eight
      of the 2-min daily runs they attempted the reversed visual tracking task. VOR
      gain was measured during the 1st, 6th and last runs which were conducted in the
      dark for this purpose. Constancy of EOG gain was maintained by using red light
      throughout.6. The results of B showed a substantial (approx. 25%) and highly
      significant (P << 0.001) reduction of VOR gain attributable solely to the 16 min
      of reversed visual tracking attempted during the 50 min daily experiment. In
      addition the pre-test control gain was lower on day 3 than on day 1 (approx. 10%
      attenuation, P < 0.01) indicating a small cumulative effect from beginning to end
      of the 3-day experiment.7. It is concluded (A) that the repeated vestibular
      stimulus did not itself cause significant attenuation of VOR gain, but (B) that
      superposition of a reversed visual tracking task did induce retained VOR
      attenuation which was solely due to the antagonistic visual stimulus.8. In
      conjunction with other experimental evidence it is inferred that this attenuation
      probably represents an adaptive change in the VOR induced at least in part by
      retinal image slip.

PMID- 16992508
TI  - Extreme vestibulo-ocular adaptation induced by prolonged optical reversal of
      vision.
AB  - 1. These experiments investigated plastic changes in the vestibulo-ocular reflex
      (VOR) of human subjects consequent to long-term optical reversal of vision during
      free head movement. Horizontal vision-reversal was produced by head-mounted dove
      prisms. Four normal adults were continuously exposed to these conditions during
      2, 6, 7 and 27 days respectively.2. A sinusoidal rotational stimulus, previously
      shown to be nonhabituating (1/6 Hz; 60 degrees /sec amplitude), was used to test
      the VOR in the dark at frequent intervals both during the period of vision
      reversal and an equal period after return to normal vision. D.c. electro
      oculography (EOG) was used to record eye movement, taking care to avoid changes
      of EOG gain due to light/dark adaptation of the retina.3. All subjects showed
      substantial reduction of VOR gain (eye velocity/head velocity) during the first 2
      days of vision-reversal. The 6-, 7- and 27-day subjects showed further reduction
      of gain which reached a low plateau at about 25% the normal value by the end of
      one week. At this time the attenuation of some EOG records was so marked as to
      defy extraction of a meaningful sinusoidal signal.4. After removal of the prisms
      VOR gain recovered along a time course which approximated that of the original
      adaptive attenuation.5. In the 27-day experiment large changes of phase developed
      in the VOR during the second week of vision-reversal. These changes generally
      progressed in a lagging sense, to reach 130 degrees phase lag relative to normal
      by the beginning of the third week. Accompanying this was a considerable
      restoration of gain from 25 to 50% the normal value. These adapted conditions,
      which approximate functional reversal of the reflex, were then maintained steady,
      even overnight, until return to normal vision on the 28th day.6. Thereafter,
      whereas VOR phase returned to near-normal in 2 hr, restoration of gain occupied a
      further 2-3 weeks.7. There was a highly systematic relation between instantaneous
      gain and phase, even during periods of widely fluctuating change associated with
      transition from one steady state to another. During such transition there was a
      tendency for directional preponderance to occur in the VOR.8. All the observed
      changes were highly specific to the plane of vision-reversal, no VOR changes
      being observed in the sagittal plane.9. VOR changes were adaptive, in the sense
      that they were always goal-directed towards the requirements of retinal image
      stabilization during head movement. They were plastic to the extent that there
      was extensive and retained remodelling of the reflex towards this goal.10. It is
      inferred that all the observed changes in gain and phase are compatible with a
      simple neural network employing known vestibulo-ocular projections via brainstem
      and cerebellar pathways, providing that the reversed visual tracking task can
      produce plastic modulation of efficacy in the cerebellar pathway and that this
      pathway exhibits a dynamic characteristic producing moderate phase lead in a
      sinusoidal signal at 1/6 Hz.

PMID- 16992509
TI  - Genetic dissection of the photoreceptor system in the compound eye of Drosophila
      melanogaster.
AB  - Three mutations which eliminate specific types of photoreceptors in Drosophila
      were characterized. Of the eight photoreceptors in each facet, two mutations
      delete the outer six (R 1-6). The third eliminates R 7, one of the two central
      photoreceptors. Double mutants can be constructed in which only photoreceptor R 8
      is present. The spectral sensitivities, photopigments, and behavioural properties
      of these mutants were investigated. R 1-6 have two sensitivity peaks, near 350
      and 470 nm. These receptors contain a rhodopsin with these absorption peaks. It
      interconverts with a metarhodopsin that absorbs around 570 nm. R 7 is a U.V.
      receptor, containing rhodopsin that absorbs around 370 nm and interconverts with
      a metarhodopsin which absorbs around 470 nm. R 8 is a non-adapting blue-receptor
      with a third type of rhodopsin. The properties of these photopigments explain the
      different sensitivities and spectral adaptation phenomena of the various
      photoreceptors. All the photoreceptors have input into phototaxis. Spectral
      analysis of this behaviour provides evidence for integration of the input from
      the different photoreceptors.

PMID- 16992510
TI  - Chloride distribution in Aplysia neurones.
AB  - 1. The intracellular Cl(-) concentration (Cl(i)) and the membrane potential
      (E(m)) were measured in the medial pleural neurones of Aplysia under various
      experimental conditions designed to determine the Cl(-) conductance of the
      neurones and investigate the possibility of an active Cl(-) transport.2. The
      magnitude of the Cl(-) conductance of the cell depends on the experimental
      conditions.3. In normal sea water, large changes of E(m) produced by passing
      current across the cell membrane caused no change of Cl(i), suggesting that the
      Cl(-) conductance was low. Similarly, moderate changes of E(Cl) produced by
      decreasing Cl(o) or increasing Cl(i) had little or no effect on E(m).4. A high
      Cl(-) conductance was observed in high K(o) or very low Cl(o). It was greatly
      reduced if the external Ca(2+) was replaced by Co(2+), or in the presence of
      tubocurarine, or if the experiment was performed on an isolated cell soma. The
      high Cl(-) conductance is therefore attributed to the release of ACh and perhaps
      other transmitters from synaptic terminals.5. High concentrations of
      tetraethylammonium ions or procaine induced a depolarization of the cell, but a
      decrease of Cl(i). The rate of fall of Cl(i) was increased by lowering external
      K(+) or raising external Ca(2+), and was decreased by replacing external Ca(2+)
      by Co(2+).6. NH(4) (+) ions applied externally had effects similar to those of
      K(+) ions. In situations in which intracellular NH(4) (+) might be increased a
      fall in Cl(i) was observed.7. The changes of Cl(i) caused by TEA, procaine, or
      internal NH(4) (+) occur against the driving force for passive Cl(-) movements.
      They are still observed in isolated cell bodies, and cannot be attributed to the
      activation of synaptic channels.8. Some interpretations of these anomalous Cl(-)
      movements are discussed which could also account for the difference between E(Cl)
      and E(m) observed under normal conditions.

PMID- 16992511
TI  - ATP hydrolysis associated with an uncoupled sodium flux through the sodium pump:
      evidence for allosteric effects of intracellular ATP and extracellular sodium.
AB  - 1. A method has been developed for regenerating [gamma(32)P]ATP of constant
      specific activity within resealed red cell ghosts, and for measuring its
      hydrolysis. The method may be used to follow the hydrolysis of ATP at
      concentrations down to 1 muM, and for periods long enough for the ATP at these
      very low concentrations to turn over several hundred times.2. Using this method
      we have been able to show that the ;uncoupled' efflux of Na caused by the Na pump
      when resealed red cell ghosts are incubated in (Na + K)-free media is associated
      with a hydrolysis of ATP. The stoicheiometry is roughly 2-3 Na ions expelled per
      molecule of ATP hydrolysed.3. Measurements of ATP hydrolysis and Na efflux as
      functions of intracellular ATP concentration have shown that uncoupled Na efflux,
      and its associated ATP hydrolysis, are saturated at intracellular ATP
      concentrations in the region of 1 muM.4. Measurement of ATP hydrolysis as a
      function of ATP concentration in resealed ghosts incubated in a K-containing
      medium gave a complicated activation curve suggesting the involvement of high
      affinity (K(m)ca. 1 muM) and low-affinity (K(m)ca. 100 muM) sites.5. When
      resealed ghosts containing about 1 muM-ATP were incubated in a Na-free or in a
      high-Na medium, the addition of K to the medium reduced the rate of ouabain
      sensitive ATP hydrolysis.6. Ouabain-sensitive ATP hydrolysis in resealed ghosts
      incubated in K-free choline media was inhibited by external Na at low
      concentrations (K(i) < 1 mM), but this inhibition was reversed as the external Na
      concentration was further increased.7. The results show that uncoupled Na efflux
      may be thought of as the transport mode associated with Na-ATPase activity, just
      as Na-K exchange is the transport mode associated with (Na + K)-ATPase activity.
      The significance of the differences between uncoupled Na efflux and Na-ATPase
      activity, on the one hand, and Na-K exchange and (Na + K)-ATPase activity, on the
      other, is discussed.

PMID- 16992512
TI  - Contributions to the physiological effects of peptone when injected into the
      circulation: Part IV. The local vascular influences of peptone and proteoses
      (contd.): effects on the splenic, hepatic, and limb districts.

PMID- 16992513
TI  - On the innervation of the longitudinal coat of the small intestine.

PMID- 16992514
TI  - The effect of compression on one lung on respiratory gas exchange.

PMID- 16992516
TI  - Auto-intoxication as the cause of pancreatic diabetes: Preliminary communication.

PMID- 16992515
TI  - On periodic variations in the contractions of the mammalian heart.

PMID- 16992517
TI  - The physiological action of the alkaloids derived from Anhalonium Lewinii.

PMID- 16992519
TI  - Further proofs of the origin of uric acid from nuclein-compounds and derivatives.

PMID- 16992518
TI  - The physiological effects of extracts of the pituitary body.

PMID- 16992520
TI  - The metabolism of the nucleins: Part II. Further observations on excretion in
      leucocythaemia. Intracellular metabolism in the granular leucocytes.

PMID- 16992521
TI  - The death temperature of certain marine-organisms.

PMID- 16992522
TI  - The efficiency of the contraction of veratrinised muscle.

PMID- 16992523
TI  - The action of the vagus and the sympathetic on the oesophagus of the toad.

PMID- 16992525
TI  - Contributions to the physiological effects of peptone when injected into the
      circulation: Part V. The influence of peptone and albumoses on the urinary
      secretion.

PMID- 16992524
TI  - The influence of bile, of acids, and of alkalis on the proteolytic action of
      pancreatic juice.

PMID- 16992526
TI  - On chromatolysis in Deiters' nucleus after hemisection of the cord.

PMID- 16992528
TI  - The pressure-filtration of proteids: Preliminary communication.

PMID- 16992527
TI  - On some numerical comparisons of the centripetal and centrifugal medullated nerve
      fibres arising in the spinal ganglia of the mammal.

PMID- 16992529
TI  - Contributions to the study of the metabolism of phosphorus in the animal body.

PMID- 16992530
TI  - The supposed oxidation of carbonic oxide in the living body.

PMID- 16992531
TI  - On cyanmethaemoglobin and photomethaemoglobin.

PMID- 16992532
TI  - Further researches on the physiology of the mammalian heart: Part I. On the
      influence of chloroform upon the rate of the heart-beat, with some observations
      on the effects of asphyxia, &c.

PMID- 16992533
TI  - The gaseous metabolism of the submaxillary gland: Part I. On methods, with a
      description of an apparatus for gas analysis.

PMID- 16992534
TI  - The physiological effects of extracts of nervous tissues.

PMID- 16992535
TI  - The ferricyanide method of determining the oxygen capacity of blood.

PMID- 16992536
TI  - Note on the regeneration of the vagus nerve.

PMID- 16992537
TI  - On the separation of a pure albumin from egg-white.

PMID- 16992538
TI  - The mass and oxygen capacity of the blood in man.

PMID- 16992540
TI  - A note on the physiological action of Poehl's spermine.

PMID- 16992539
TI  - An experimental research on excretion in the small intestine.

PMID- 16992541
TI  - On axon-reflexes in the pre-ganglionic fibres of the sympathetic system.

PMID- 16992542
TI  - The influence of sodium salicylate on general metabolism.

PMID- 16992543
TI  - Notes on the regeneration of the pre-ganglionic fibres in the sympathetic system.

PMID- 16992544
TI  - A physical theory of nerve.

PMID- 16992545
TI  - Studies of the metabolism in the dog before and after removal of the spleen.

PMID- 16992546
TI  - Further observations on the structural alterations in the cells of the spinal
      cord following various nerve lesions: Part III.

PMID- 16992547
TI  - Remarks on the results of degeneration of the upper thoracic white rami
      communicantes, chiefly in relation to commissural fibres in the sympathetic
      system.

PMID- 16992548
TI  - The gaseous metabolism of the submaxillary gland: Part II. On the absorption of
      water from the blood during its passage through the active gland.

PMID- 16992549
TI  - Diuretic effects of sodium chloride solutions: an inquiry into the relation which
      certain factors bear to renal activity.

PMID- 16992550
TI  - Galvanotaxis and chemotaxis of ciliate infusoria: Part I.

PMID- 16992552
TI  - On dilatation of the pupil from stimulation of the cortex cerebri.

PMID- 16992551
TI  - The action of ether and chloroform on the cerebral and spinal neurons of dogs:
      Supplementary Paper.

PMID- 16992553
TI  - The physiological properties of the muscle of echidna hystrix.

PMID- 16992555
TI  - The conditions of action of "trypsin" on fibrin.

PMID- 16992554
TI  - A further enquiry into the supposed existence of cerebral vasomotor nerves.

PMID- 16992556
TI  - Intestinal absorption of maltose.

PMID- 16992557
TI  - Transport of fluid by certain epithelia.

PMID- 16992558
TI  - Observations upon the chemistry and heat rigor curves of vertebrated muscle,
      involuntary and voluntary.

PMID- 16992559
TI  - On the presence of nerve-fibres in the cerebral vessels.

PMID- 16992560
TI  - The conditions that underlie the peculiarities in the behaviour of the coloured
      blood-corpuscles to certain substances.

PMID- 16992561
TI  - The colorimetric determination of haemoglobin.

PMID- 16992562
TI  - On the changes in volume of the submaxillary gland during activity.

PMID- 16992564
TI  - The effect of temperature on the functional activity of the upper cervical
      ganglion.

PMID- 16992563
TI  - The movements and the innervation of the large intestine.

PMID- 16992565
TI  - The action of ether and chloroform on the neurons of rabbits and dogs.

PMID- 16992566
TI  - The position of the respiratory and cardio-inhibitory fibres in the rootlets of
      the IXth, Xth, and XIth cranial nerves.

PMID- 16992567
TI  - The immediate action of an intravenous injection of blood-serum.

PMID- 16992568
TI  - The influence in voluntary muscle of the intra-polar length on the excitatory
      effect of the constant current.

PMID- 16992569
TI  - Observations on the lymph flow from the submaxillary gland of the dog.

PMID- 16992570
TI  - On reflex cardiac inhibition.

PMID- 16992571
TI  - The movements and innervation of the small intestine.

PMID- 16992572
TI  - On the effects of venous obstruction on the secretion of urine.

PMID- 16992573
TI  - On metabolism in forced feeding.

PMID- 16992574
TI  - On a method of estimating the interference with the hepatic metabolism produced
      by drugs.

PMID- 16992575
TI  - On the origin from the spinal cord of the vaso-dilator fibres of the hind-limb,
      and on the nature of these fibres.

PMID- 16992576
TI  - An attempt to estimate fatigue of the cerebral cortex when caused by electrical
      excitation.

PMID- 16992577
TI  - The physiological effects of extracts of nervous tissues.

PMID- 16992578
TI  - The composition and action of orchitic extracts.

PMID- 16992579
TI  - On the action of iodine and iodides chiefly with regard to the muscles of frog.

PMID- 16992580
TI  - On the nature of the sugar present in normal blood, urine and muscle.

PMID- 16992581
TI  - Gelatine filters.

PMID- 16992582
TI  - The conditions of action of pancreatic rennin and diastase.

PMID- 16992583
TI  - Some contributions to the physiology of unstriated muscle.

PMID- 16992584
TI  - On the stimulation and paralysis of nerve-cells and of nerve-endings: Part I.

PMID- 16992585
TI  - Observations on the physiological action of extracts of the supra-renal bodies.

PMID- 16992586
TI  - The isometric value of active muscle excited directly and indirectly.

PMID- 16992587
TI  - On diuresis and the permeability of the renal cells.

PMID- 16992588
TI  - An experimental enquiry upon glycolysis in drawn blood.

PMID- 16992589
TI  - On the question of the formation of sugar in boiled liver.

PMID- 16992590
TI  - Specific gravity of the brain.

PMID- 16992591
TI  - Reticulin and collagen.

PMID- 16992592
TI  - On recording variations in volume by air-transmission. A new form of volume
      recorder.

PMID- 16992593
TI  - On the influence of temperature on the conductivity of nerve.

PMID- 16992594
TI  - On the estimation of sodium and potassium in urine.

PMID- 16992595
TI  - The nervous system of the dog without a forebrain.

PMID- 16992596
TI  - On the film or "skin" of warmed milk and of other proteid solutions.

PMID- 16992597
TI  - The gaseous metabolism of the submaxillary gland.

PMID- 16992598
TI  - An apparatus for artificial respiration and for other purposes.

PMID- 16992599
TI  - A method of obtaining intracellular juices.

PMID- 16992600
TI  - On the precipitation of proteids with anhydrous sulphate of sodium.

PMID- 16992601
TI  - Observations upon the respiration and temperature of the marmot.

PMID- 16992603
TI  - The benzoylation of alkapton urine.

PMID- 16992602
TI  - Note on a new form of aesthesiometer.

PMID- 16992604
TI  - The electrical response of muscle in different kinds of persistent contraction.

PMID- 16992605
TI  - The conditions of conversion of pancreatic zymogens into enzymes.

PMID- 16992606
TI  - On the agents concerned in the production of the tryptic ferment from its
      zymogen.

PMID- 16992607
TI  - Rigor mortis in the heart and the state of the cardiac cavities after death.

PMID- 16992609
TI  - Note on the percentage composition of egg-yolk.

PMID- 16992608
TI  - Observations, chiefly by the degeneration method, on possible efferent fibres in
      the dorsal nerve-roots of the toad and frog.

PMID- 16992610
TI  - The spinal roots and dissociative anaesthesia in the monkey.

PMID- 16992612
TI  - Caseinogen and its salts.

PMID- 16992611
TI  - An experimental research into the relations of the posterior longitudinal bundle
      and Deiters' nucleus.

PMID- 16992613
TI  - The respiratory exchange during the deposition of fat.

PMID- 16992614
TI  - A contribution to the chemistry of proteids: Part I. A preliminary study of a
      hitherto undescribed product of tryptic digestion.

PMID- 16992615
TI  - Fatigue in non-medullated nerves.

PMID- 16992616
TI  - Note on foetal muscle spindles.

PMID- 16992618
TI  - On the local reactions of the arterial wall to changes of internal pressure.

PMID- 16992617
TI  - On the formation of lymph by the liver.

PMID- 16992619
TI  - A method of estimating the oxygen and carbonic acid in small quantities of blood.

PMID- 16992620
TI  - Intestinal absorption of solutions.

PMID- 16992621
TI  - Metabolism on ordinary and forced diets in normal individuals.

PMID- 16992622
TI  - Further researches on antidromic nerve-impulses.

PMID- 16992624
TI  - On the innervation of the urinary passages in the dog.

PMID- 16992623
TI  - Taste and the fifth nerve.

PMID- 16992625
TI  - The visual acuity of the natives of Sarawak.

PMID- 16992626
TI  - Reticulin and collagen.

PMID- 16992627
TI  - The mechanism of pancreatic secretion.

PMID- 16992628
TI  - The influence of oxygen upon the survival respiration of muscle.

PMID- 16992630
TI  - A further note on the pyramidal tract (Monakow's bundle).

PMID- 16992629
TI  - On the products of the proteolytic action of an enzyme contained in the cells of
      the spleen.

PMID- 16992631
TI  - The conditions of action of the pancreatic secretion.

PMID- 16992632
TI  - The submaximal electrical response of nerve to a single stimulus.

PMID- 16992633
TI  - On the pitch of Galton-whistles.

PMID- 16992634
TI  - A preliminary communication on the changes in nerve cells after poisoning with
      the venom of the Australian tiger-snake (Hoplocephalus curtus).

PMID- 16992635
TI  - On saline diuresis.

PMID- 16992636
TI  - Pancreatic zymogens and pro-zymogens.

PMID- 16992638
TI  - The nature of the lesions which hinder the development of nerve-cells and their
      processes.

PMID- 16992637
TI  - The relation of oxygen to the survival metabolism of muscle.

PMID- 16992639
TI  - On the effect exerted on the coagulability of the blood by an admixture of lymph.

PMID- 16992640
TI  - A further research into fatigue of the central nervous system when caused by
      electrical stimulation.

PMID- 16992641
TI  - The influence of subcutaneous injections of large quantities of dextrose on the
      metabolism in the dog.

PMID- 16992642
TI  - Note on the absorption of the nitrogen of oatmeal by the dog.

PMID- 16992643
TI  - On the residual pressures in the vascular system when the circulation is
      arrested.

PMID- 16992644
TI  - Pancreatic diastase, and its zymogen.

PMID- 16992645
TI  - Path of impulses for inhibition under decerebrate rigidity.

PMID- 16992646
TI  - The differences of action of various diastases.

PMID- 16992647
TI  - On the digestion of cane sugar.

PMID- 16992649
TI  - The effect of local injury upon the excitatory electrical response of nerve.

PMID- 16992648
TI  - Some effects of the ligature of the renal arteries in the frog.

PMID- 16992650
TI  - The innervation of the frog's stomach.

PMID- 16992651
TI  - Some experiments on the functions of the medulla of the kidney.

PMID- 16992652
TI  - The relationship of the spleen to the formation of the blood corpuscles.

PMID- 16992653
TI  - The sugars of muscle.

PMID- 16992655
TI  - The effect of haemorrhage upon the composition of the normal blood, compared to
      its effect during the administration of iron and arsenic.

PMID- 16992654
TI  - Cortex cerebri and iris.

PMID- 16992656
TI  - On the physiological action of the Kenyah dart poison ipoh, and its active
      principle antiarin.

PMID- 16992657
TI  - Observations on some spinal reflexes and the interconnection of spinal segments.

PMID- 16992658
TI  - Further observations on the sequence of changes produced in the urine as a result
      of exercise.

PMID- 16992659
TI  - On the uniformity of the pancreatic mechanism in vertebrata.

PMID- 16992660
TI  - The estimation of urea in blood.

PMID- 16992661
TI  - Remarks on the dorsal spino-cerebellar tract.

PMID- 16992662
TI  - Further observations upon the respiratory exchange and temperature of hibernating
      mammals.

PMID- 16992663
TI  - Contributions to the physiology of the lungs: Part I. The bronchial muscles,
      their innervation, and the action of drugs upon them.

PMID- 16992664
TI  - On the inorganic composition of the Medusae, Aurelia flavidula and Cyanea
      arctica.

PMID- 16992665
TI  - The effects of intravascular injections of extracts of animal tissues.

PMID- 16992666
TI  - The perfusion of surviving organs.

PMID- 16992667
TI  - On the formation of glycogen in the artificially perfused liver.

PMID- 16992668
TI  - The spinal origin of the cervical sympathetic nerve.

PMID- 16992670
TI  - The precipitability of pancreatic ferments by alcohol.

PMID- 16992669
TI  - On the nature of adrenalin glycosuria.

PMID- 16992671
TI  - On the mechanism of phloridzin glycosuria.

PMID- 16992672
TI  - The influence of compressed air on the respiratory exchange.

PMID- 16992673
TI  - Some further observations on the reaction of urochrome with acetaldehyde.

PMID- 16992674
TI  - An experimental enquiry into the formation of gall-stones.

PMID- 16992675
TI  - The role of the liver and spleen in the destruction of the blood corpuscles.

PMID- 16992676
TI  - Poikilothermism in rabies.

PMID- 16992677
TI  - The influence of ablation of the liver on the sugar contents of the blood.

PMID- 16992679
TI  - The time relations of the photo-electric changes in the eyeball of the frog.

PMID- 16992678
TI  - The influence of compressed air and oxygen on the gases of the blood.

PMID- 16992680
TI  - The spleen in relationship to the processes of haemolysis.

PMID- 16992682
TI  - A contribution to the chemistry of proteids: Part II. The constitution of
      tryptophane, and the action of bacteria upon it.

PMID- 16992681
TI  - On some effects of the constituents of Ringer's circulating fluid on skeletal
      muscular contractions in Rana hexadactyla.

PMID- 16992683
TI  - Digestion leucocytosis in normal and in spleenless dogs.

PMID- 16992685
TI  - Reflex pupil-dilatation by way of the cervical sympathetic nerve.

PMID- 16992684
TI  - The estimation of potassium and sodium in urine and in other material of organic
      origin.

PMID- 16992686
TI  - The precipitation of proteids by alcohol and certain other reagents.

PMID- 16992687
TI  - Qualitative difference of spinal reflex corresponding with qualitative difference
      of cutaneous stimulus.

PMID- 16992688
TI  - The formation of uric acid in birds.

PMID- 16992689
TI  - The proteolytic activities of the pancreatic juice.

PMID- 16992690
TI  - The products of the proteolytic action of an enzyme contained in the cells of the
      kidney.

PMID- 16992691
TI  - A method to demonstrate the changes in the vascularity of the submaxillary gland
      on stimulation of the secretory nerves.

PMID- 16992692
TI  - The nature of the physiologically active substances in extracts of nervous
      tissues and blood, with some remarks on the methods of testing for choline.

PMID- 16992693
TI  - Investigations on the proteolytic enzymes of the spleen of the ox.

PMID- 16992694
TI  - Atropine and the hyoscyamines-a study of the action of optical isomers.

PMID- 16992695
TI  - On the presence of a proteolytic enzyme in the normal serum of the ox.

PMID- 16992696
TI  - Contributions to our knowledge of the action of enzymes: Part I. The influence of
      electrolytes on the action of amylolytic ferments.

PMID- 16992697
TI  - The paralysis of nerve cells and nerve endings with special reference to the
      alkaloid apocodeine.

PMID- 16992698
TI  - On the sympathetic system of birds, and on the muscles which move the feathers.

PMID- 16992699
TI  - The hydrolysis of optically inactive esters by means of enzymes: Part I. The
      action of lipase upon esters of mandelic acid. The resolution of inactive
      mandelic acid.

PMID- 16992700
TI  - On the question of the direct action of tissue extracts on protoplasm.

PMID- 16992701
TI  - On the influence of pituitary gland substance on metabolism.

PMID- 16992702
TI  - Contributions to our knowledge of the action of enzymes: Part II. The influence
      of electrolytes on the action of invertin.

PMID- 16992704
TI  - On certain colour reactions of proteid due to tryptophane.

PMID- 16992703
TI  - The paralysis of involuntary muscle, with special reference to the occurrence of
      paradoxical contraction: Part I. Paradoxical pupildilatation and other ocular
      phenomena caused by lesions of the cervical sympathetic tract.

PMID- 16992705
TI  - On the haemoglobinometry and haemacytometry of the blood of the skate.

PMID- 16992706
TI  - The haemoglobin and corpuscular content of the blood of the newborn.

PMID- 16992707
TI  - The peptone-splitting ferments of the pancreas and intestine.

PMID- 16992708
TI  - On the number of nodes of Ranvier in different stages of the growth of nerve
      fibres in the frog.

PMID- 16992709
TI  - Intravascular injection of salts and of nucleo-proteid.

PMID- 16992710
TI  - The relationship of blood-supply to secretion, with especial reference to the
      pancreas.

PMID- 16992711
TI  - The osmotic properties of muscle, and their modifications in fatigue and rigor.

PMID- 16992712
TI  - On the union of the fifth cervical nerve with the superior cervical ganglion.

PMID- 16992713
TI  - On the influence of tension upon the contraction of skeletal muscle at high
      temperatures.

PMID- 16992714
TI  - The action of the rays from radium upon some simple forms of animal life.

PMID- 16992715
TI  - A modification of Professor Schafer's frog heart plethysmograph, with some
      observations on the method of using it.

PMID- 16992716
TI  - On some effects of the constituents of Ringer's circulating fluid on the plain
      muscle of Rana tigrina.

PMID- 16992717
TI  - Contributions to the physiology of the lungs: Part II. On the innervation of the
      pulmonary blood vessels; and some observations on the action of suprarenal
      extract.

PMID- 16992718
TI  - Note on the ultimate fate of ventral cornual cells after section of a number of
      posterior roots.

PMID- 16992719
TI  - The time-relations of the photo-electric changes produced in the eyeball of the
      frog by means of coloured light.

PMID- 16992720
TI  - On protagon, cholin and neurin.

PMID- 16992721
TI  - The function of the hyaloid canal and some other new points in the mechanism of
      the accommodation of the eye for distance.

PMID- 16992722
TI  - Contribution to the physiology of the thymus.

PMID- 16992723
TI  - On the physiological action of the alkaloids of jaborandi leaves.

PMID- 16992724
TI  - On the innervation of the ileo-colic sphincter.

PMID- 16992725
TI  - The formation of prussic acid by the oxidation of albumins.

PMID- 16992726
TI  - The histological changes produced by the injection of adrenalin chloride.

PMID- 16992727
TI  - Observations on the influence of adrenalin poisoning on the liver, with special
      reference to the glycogen.

PMID- 16992728
TI  - On the adaptation of the pancreas.

PMID- 16992729
TI  - The influence of changes in the intraocular circulation on the intraocular
      pressure.

PMID- 16992730
TI  - The influence of fasting and feeding upon the respiratory and nitrogenous
      exchange.

PMID- 16992731
TI  - The protective value of proteids and their decomposition products on trypsin.

PMID- 16992732
TI  - On the action of oxygen at low and high pressure upon the corneal endothelium.

PMID- 16992733
TI  - The union of different kinds of nerve fibres.

PMID- 16992734
TI  - The elasticity of animal tissues.

PMID- 16992735
TI  - On the "sham-death" reflex in spiders.

PMID- 16992736
TI  - On autogenetic regeneration in the nerves of the limbs.

PMID- 16992737
TI  - The action of pituitary extracts on the heart and circulation of the frog.

PMID- 16992738
TI  - Osmotic pressure of solutions containing native proteids.

PMID- 16992739
TI  - Some observations on blood pigments.

PMID- 16992740
TI  - Heat contraction in nerve.

PMID- 16992741
TI  - The oxygen exchange of the pancreas.

PMID- 16992743
TI  - Some researches on the autolytic degradation of tissues: Part I.

PMID- 16992742
TI  - On the antitryptic action of normal serum.

PMID- 16992744
TI  - On the secretion of acid by the kidney.

PMID- 16992745
TI  - Studies on the maintenance of the equilibrium of motion and its disturbances, so
      called "forced movements.".

PMID- 16992746
TI  - On the relationship of the thymus to the sexual organs: I. The influence of
      castration on the thymus.

PMID- 16992747
TI  - On the composition of pancreatic juice.

PMID- 16992749
TI  - On the question of commissural fibres between nerve-cells having the same
      function and situated in the same sympathetic ganglion, and on the function of
      post-ganglionic nerve plexuses.

PMID- 16992748
TI  - A pseudaffective reflex and its spinal path.

PMID- 16992750
TI  - The innervation of the sphincters and musculature of the stomach.

PMID- 16992751
TI  - Antiperistalsis and other muscular activities of the colon.

PMID- 16992752
TI  - The lymph-flow from the pancreas.

PMID- 16992753
TI  - The gaseous metabolism of the kidney.

PMID- 16992755
TI  - The universal presence of erepsin in animal tissues.

PMID- 16992754
TI  - The relationship of the thymus to the sexual organs: II. The influence of removal
      of the thymus on the growth of the sexual organs.

PMID- 16992756
TI  - The formation of prussic acid by the oxidation of albumins: II.

PMID- 16992757
TI  - The effect of adrenalin on sugar and nitrogen excretion in the urine of birds.

PMID- 16992758
TI  - Some observations upon the functions of the thyroid and parathyroid glands.

PMID- 16992759
TI  - The changes in the viscosity of the blood produced by alcohol.

PMID- 16992760
TI  - The selective action of cocaine on nerve fibres.

PMID- 16992761
TI  - On the relation of enterokinase to trypsin.

PMID- 16992762
TI  - The physiological effects of peptone and allied products: Part VI. The metabolism
      of arginin.

PMID- 16992763
TI  - The action of anaesthetic quantities of chloroform upon the blood vessels of the
      bowel and kidney; with an account of an artificial circulation apparatus.

PMID- 16992764
TI  - Researches on the autolytic degradation of tissues: Part II. On the influence of
      the thyroid on autolysis.

PMID- 16992765
TI  - Effect on blood-pressure of proteolytic products.

PMID- 16992767
TI  - On the inter-relationship of calcium and magnesium excretion.

PMID- 16992766
TI  - Experiments on cystin and its relation to sulphur metabolism.

PMID- 16992769
TI  - On the distribution of potassium in animal and vegetable cells.

PMID- 16992768
TI  - The post-natal changes in the thymus of guinea-pigs, and the effect of castration
      on thymus structure.

PMID- 16992770
TI  - The fractional hydrolysis of optically inactive esters by lipase: Part II.

PMID- 16992771
TI  - Observations upon fibrin-ferments in the venoms of snakes and the time-relations
      of their action.

PMID- 16992772
TI  - On the formation of fatty acids from lactic acid when fused with caustic
      alkalies.

PMID- 16992773
TI  - Note on Neumann's method of estimating chloride.

PMID- 16992774
TI  - The regulation of the lung-ventilation.

PMID- 16992775
TI  - The separation of proteids.

PMID- 16992776
TI  - On the products of digestion of the proteolytic spleen enzyme acting in an
      alkaline medium.

PMID- 16992777
TI  - The effect of cold narcosis on reflex action in warm-blooded animals.

PMID- 16992779
TI  - Observations on the munchi arrow poison.

PMID- 16992778
TI  - The effects of acids upon blood.

PMID- 16992780
TI  - On the chemical specificity of precipitins.

PMID- 16992781
TI  - Observations on the gaseous metabolism of the small intestine of the rabbit.

PMID- 16992782
TI  - On the efferent relationship of the optic thalamus and Deiter's nucleus to the
      spinal cord, with special reference to the cerebellar influx of Dr Hughlings
      Jackson and the genesis of the decerebrate rigidity of Ord and Sherrington.

PMID- 16992783
TI  - The changes in the viscosity of the blood during narcosis.

PMID- 16992785
TI  - The cilioscribe, an instrument for recording the activity of cilia.

PMID- 16992784
TI  - On the antitryptic action of serum-albumin.

PMID- 16992786
TI  - The action of adrenalin.

PMID- 16992788
TI  - The normal alveolar carbonic acid pressure in man.

PMID- 16992787
TI  - Observations on the action of trypsin.

PMID- 16992789
TI  - The human cardiopneumatic movements.

PMID- 16992791
TI  - On Folin's theory of proteid metabolism.

PMID- 16992790
TI  - The action of optical isomers: II. Hyoscines.

PMID- 16992792
TI  - Osmotic pressure of solutions of haemoglobin.

PMID- 16992793
TI  - Digestion leucocytosis: II. The source of the leucocytes.

PMID- 16992794
TI  - Some observations of the movements of the intestine before and after degenerative
      section of the mesenteric nerves.

PMID- 16992795
TI  - The gaseous metabolism of the kidney.

PMID- 16992796
TI  - The response of the developing retina to light and to radium emanations.

PMID- 16992797
TI  - Degeneration of nerve-cells of the rabbit's superior cervical sympathetic
      ganglion as the result of interfering with their blood supply.

PMID- 16992798
TI  - On the globulin of "albuminous" urine.

PMID- 16992799
TI  - The physiological effects of peptone and allied products: Part VII. The
      metabolism of arginin (contd.).

PMID- 16992800
TI  - On the gradation of activity in a skeletal muscle-fibre.

PMID- 16992802
TI  - The paralysis of involuntary muscle: Part II. On paralysis of the sphincter of
      the pupil with special reference to paradoxical constriction and the functions of
      the ciliary ganglion.

PMID- 16992801
TI  - The contractile mechanism of the gall-bladder and its extrinsic nervous control.

PMID- 16992803
TI  - The ereptic power of tissues as a measure of functional capacity.

PMID- 16992804
TI  - The factors of the ureter pressure.

PMID- 16992805
TI  - Note on the effects of pituitary feeding.

PMID- 16992806
TI  - The uniformity of the homogentisic acid excretion in alkaptonuria.

PMID- 16992808
TI  - Detection of choline in the cerebro-spinal fluid by means of the polarisation
      microscope.

PMID- 16992807
TI  - On the estimation of homogentisic acid in urine by the method of Wolkow and
      Baumann.

PMID- 16992809
TI  - New tests for choline in physiological fluids.

PMID- 16992810
TI  - An investigation into the diurnal variation of the body temperature of nocturnal
      and other birds, and a few mammals.

PMID- 16992811
TI  - On the precipitins of snake antivenoms and snake antisera.

PMID- 16992812
TI  - The separation of phosphorus from caseinogen by the action of enzymes and alkali.

PMID- 16992813
TI  - On the absorption of proteids from the intestine.

PMID- 16992815
TI  - On the mechanism of protection of intestinal worms, and its bearing on the
      relation of enterokinase to trypsin.

PMID- 16992814
TI  - On the identity of trypsinogen and enterokinase respectively, in vertebrates.

PMID- 16992816
TI  - A method for the determination of the volume of blood in animals.

PMID- 16992818
TI  - Globulin.

PMID- 16992817
TI  - Colloidal solution. The globulins.

PMID- 16992819
TI  - On the reaction of cells and of nerve-endings to certain poisons, chiefly as
      regards the reaction of striated muscle to nicotine and to curari.

PMID- 16992820
TI  - The paralysis of involuntary muscle: Part III. On the action of pilocarpine,
      physostigmine, and atropine upon the paralysed iris.

PMID- 16992821
TI  - On some physiological actions of ergot.

PMID- 16992822
TI  - The action of radium rays on tyrosinase.

PMID- 16992823
TI  - The regeneration of the blood after haemorrhage.

PMID- 16992824
TI  - On the non-uniformity in the rate of discharge of impulses from cells of the
      spinal cord poisoned with strychnine.

PMID- 16992825
TI  - Concerning cystinuria.

PMID- 16992827
TI  - On secretion in the frog's kidney.

PMID- 16992826
TI  - On the secretion of urine.

PMID- 16992828
TI  - The influence of the venae comites on the pulse tracing, with special reference
      to Valsalva's experiment, and dicrotism; a note on anacrotism.

PMID- 16992829
TI  - The factors influencing the prominence of the dicrotic wave.

PMID- 16992830
TI  - On the presence of alcohol in normal blood and tissues and its relation to
      calorifaction.

PMID- 16992831
TI  - On the influence of the relative concentration of calcium ions on the reversal of
      the polar effects of the galvanic current in paramecium.

PMID- 16992833
TI  - On the estimation of proteid in human milk.

PMID- 16992832
TI  - On the phosphorus and calcium of human milk.

PMID- 16992834
TI  - On subcutaneous injections of adrenalin.

PMID- 16992835
TI  - Observations on the scratch-reflex in the spinal dog.

PMID- 16992836
TI  - On the preparation of cholesterin from brain.

PMID- 16992837
TI  - The cholesterin of the brain.

PMID- 16992839
TI  - The chemical mechanism of gastric secretion.

PMID- 16992838
TI  - Observations on diet: The influence of diet on growth and nutrition; with an
      appendix showing the composition of the several diets.

PMID- 16992840
TI  - On the relation of nerve cells to fatigue of their nerve fibres.

PMID- 16992842
TI  - Intracellular colloidal salts.

PMID- 16992841
TI  - On the conducted disturbance in muscle.

PMID- 16992843
TI  - On the alleged adaptation of the pancreas to lactose.

PMID- 16992844
TI  - The regeneration of post-ganglionic vaso-constrictor nerves: Part I.

PMID- 16992845
TI  - The post-mortem flow of lymph.

PMID- 16992846
TI  - The influence of organ extracts of cold-blooded animals on the blood-pressure of
      dogs.

PMID- 16992847
TI  - Further observations upon the functions of the thyroid and parathyroid glands.

PMID- 16992848
TI  - The estimation of the oxygen dissolved in salt solutions.

PMID- 16992849
TI  - Experiments in examination of the ;locked-jaw' induced by tetanus toxin.

PMID- 16992850
TI  - Cortex and medulla in the suprarenal glands.

PMID- 16992851
TI  - Further observations on the time-relations in the action of trypsin.

PMID- 16992852
TI  - On the optimal electric stimuli of normal and curarised muscle.

PMID- 16992854
TI  - The gaseous metabolism of the mammalian heart: Part I.

PMID- 16992853
TI  - The physiological action of muscle extract.

PMID- 16992855
TI  - On the excretion of nitrogen, creatinine and uric acid in fever.

PMID- 16992856
TI  - Galvanotropism in the crayfish.

PMID- 16992857
TI  - A note on the adrenal gland in the rat.

PMID- 16992858
TI  - Lactic acid in amphibian muscle.

PMID- 16992859
TI  - The analysis of complex excitable tissues by their response to electric currents
      of short duration.

PMID- 16992860
TI  - On the elimination of sulphocyanates from the blood, and their supposed formation
      in the salivary glands.

PMID- 16992862
TI  - On the movements of the uterus.

PMID- 16992861
TI  - The action of alcohol on the circulation.

PMID- 16992863
TI  - On the optimal electric stimuli of muscle and nerve.

PMID- 16992864
TI  - Experimental lymphocytosis.

PMID- 16992865
TI  - On methods supposed to localize phosphorus in cells.

PMID- 16992866
TI  - On diurnal and nocturnal variations in the excretion of uric acid.

PMID- 16992867
TI  - Experiments on the isolated mammalian heart to show the relation of the inorganic
      salts to the action of the accelerator and inhibitory nerves.

PMID- 16992868
TI  - Observations on human chyle.

PMID- 16992869
TI  - On the presence of lactase in the intestines of animals and on the adaptation of
      the intestine to lactose.

PMID- 16992871
TI  - The conditions of tissue respiration.

PMID- 16992870
TI  - The haematology of carbon-monoxide poisoning.

PMID- 16992872
TI  - The importance of individual amino-acids in metabolism: Observations on the
      effect of adding tryptophane to a dietary in which zein is the sole nitrogenous
      constituent.

PMID- 16992873
TI  - The innervation of the bladder and urethra.

PMID- 16992874
TI  - The functions of the epiglottis and of the glosso-epiglottic fossae.

PMID- 16992875
TI  - The regeneration of post-ganglionic vaso-constrictor nerves: Part II.

PMID- 16992876
TI  - Choline in cerebro-spinal fluid.

PMID- 16992877
TI  - The physical properties of horse serum.

PMID- 16992878
TI  - On metabolism during starvation: I. Nitrogenous.

PMID- 16992879
TI  - The non-existence of ;protagon' as a definite chemical compound.

PMID- 16992880
TI  - On the nature of the fat contained in the liver, kidney, and heart.

PMID- 16992881
TI  - Metabolism during starvation: Part II. Inorganic.

PMID- 16992883
TI  - The Haldane-Smith method of estimating the oxygen tension of the arterial blood.

PMID- 16992882
TI  - The action of caffeine on the capacity for muscular work.

PMID- 16992884
TI  - On sulphhaemoglobin.

PMID- 16992886
TI  - Wave-like variations in muscular fatigue curves.

PMID- 16992885
TI  - Concerning cystinuria and diamines.

PMID- 16992887
TI  - On the development of the plexiform nerve mechanism of the alimentary canal.

PMID- 16992889
TI  - Observations on the refractory period of the sartorius of the frog.

PMID- 16992888
TI  - The analysis of oxygen and carbonic acid contained in small volumes of saline
      solutions.

PMID- 16992890
TI  - On the occurrence of compensatory hypertrophy in the ovary.

PMID- 16992892
TI  - Creatin and creatinin.

PMID- 16992891
TI  - Effect of strychnine on muscular work.

PMID- 16992893
TI  - On the physiological action of the seeds of garcia nutans, omphalea megacarpa and
      omphalea triandra from Trinidad.

PMID- 16992894
TI  - Genesis of the alternating pulse.

PMID- 16992895
TI  - The excitable substances of amphibian muscle.

PMID- 16992897
TI  - A method of quantitative estimation of cystin in urine.

PMID- 16992896
TI  - On the supposed occurrence of uroleucic acid in the urine in some cases of
      alkaptonuria.

PMID- 16992898
TI  - On glycogen formation by yeast.

PMID- 16992899
TI  - Separation of proteins: Part II. Deutero-albumose.

PMID- 16992900
TI  - On an apparent muscular inhibition produced by excitation of the ninth spinal
      nerve of the frog, with a note on the Wedensky inhibition.

PMID- 16992901
TI  - Strychnine and reflex inhibition of skeletal muscle.

PMID- 16992902
TI  - The conditions of maintenance of maximal tissue respiration in artificial
      perfusion experiments.

PMID- 16992903
TI  - On the relation between the physical, chemical, and electrical properties of the
      nerves: Part I.

PMID- 16992904
TI  - Contributions to the physiology of the isolated heart: The consumption of
      dextrose by mammalian cardiac muscle.

PMID- 16992905
TI  - Researches on the nature of enzyme-action: I. On the causes of the rise in
      electrical conductivity under the action of trypsin.

PMID- 16992906
TI  - On the rate of variation of the exciting current as a factor in electric
      excitation.

PMID- 16992907
TI  - The effect of hirudin upon the gases in arterial blood.

PMID- 16992908
TI  - A note on the quantities of marsh-gas, hydrogen and carbon dioxide produced in
      the alimentary canal of goats.

PMID- 16992909
TI  - The precipitation of the proteins of horse serum.

PMID- 16992910
TI  - Temperature and excitability.

PMID- 16992911
TI  - On the contraction of muscle, chiefly in relation to the presence of "receptive"
      substances: Part I.

PMID- 16992913
TI  - Differential method of blood-gas analysis.

PMID- 16992912
TI  - Axon bifurcation in regenerated nerves.

PMID- 16992914
TI  - A note on the total fat of rats, guinea-pigs and mice.

PMID- 16992915
TI  - Crystalline egg-albumin.

PMID- 16992916
TI  - On the Munchi arrow poison and strophanthin.

PMID- 16992918
TI  - The temperature-coefficient of the rate of conduction in nerve.

PMID- 16992917
TI  - Colchicine with special reference to its mode of action and effect on bone
      marrow.

PMID- 16992919
TI  - The temperature coefficient of the rate of conduction and of the latent period in
      muscle.

PMID- 16992920
TI  - The action of optical isomers: III. Adrenalin.

PMID- 16992921
TI  - The structure of the autonomic nervous system compared with its functional
      activity.

PMID- 16992922
TI  - On the assimilation of protein introduced parenterally.

PMID- 16992923
TI  - On the assimilation of protein introduced enterally.

PMID- 16992924
TI  - The effect of excess of carbon dioxide and of want of oxygen upon the respiration
      and the circulation.

PMID- 16992925
TI  - On the contraction of muscle, chiefly in relation to the presence of "receptive"
      substances: Part II.

PMID- 16992926
TI  - Studies of the relationship between respiration and blood-pressure: Part I. The
      effect of changes of intra-pericardial pressure on aortic pressure.

PMID- 16992928
TI  - Note on the supposed existence of vaso-constrictor fibres in the chorda tympani
      nerve.

PMID- 16992927
TI  - Studies of the relationship between respiration and blood-pressure: Part II.
      Facts bearing on the relationship of different factors in the production of
      respiratory curves of blood-pressure.

PMID- 16992929
TI  - The excitation of vaso-dilator nerve-fibres in depressor reflexes.

PMID- 16992931
TI  - On the contraction of muscle, chiefly in relation to the presence of "receptive"
      substances: Part III. The reaction of frog's muscle to nicotine after
      denervation.

PMID- 16992930
TI  - A criticism of the nitro molybdate method for the detection of phosphorus in
      tissues.

PMID- 16992932
TI  - On the relative parts played by nervous and chemical factors in the regulation of
      respiration.

PMID- 16992933
TI  - On the death of leucocytes.

PMID- 16992934
TI  - On the vacuolation of leucocytes and the liquefaction of their cytoplasm.

PMID- 16992935
TI  - An apparatus for the perfusion of the isolated mammalian heart.

PMID- 16992936
TI  - The optical activity of so-called "protagon.".

PMID- 16992937
TI  - On a new physical phenomenon observed in connection with the optical activity of
      so-called "protagon.".

PMID- 16992938
TI  - The effects of low atmospheric pressures on respiration.

PMID- 16992940
TI  - The effects of want of exygen on respiration.

PMID- 16992939
TI  - Alveolar air on monte rosa.

PMID- 16992941
TI  - On the spontaneous movements of amphibian skeletal muscle in saline solutions,
      with observations on the influence of potassium and calcium chlorides on muscular
      excitability.

PMID- 16992942
TI  - A note on the simultaneous occurrence of sinus and ventricular rhythm in man.

PMID- 16992943
TI  - On the rate of development of the excitatory process in muscle and nerve.

PMID- 16992944
TI  - The sensibility of the stomach and intestines in man.

PMID- 16992946
TI  - The effects of muscular work upon the excretion of endogenous purines.

PMID- 16992945
TI  - Note on the sodium nitro-prusside reaction for acetone.

PMID- 16992947
TI  - The coagulation of blood.

PMID- 16992948
TI  - The transformations in the phosphorus compounds in the hen's egg during
      development.

PMID- 16992950
TI  - Further note on adrenalin isomers.

PMID- 16992949
TI  - The optical properties of the contractile elements in heliozoa.

PMID- 16992951
TI  - The natural channels of absorption evoking the chemical mechanism of gastric
      secretion.

PMID- 16992952
TI  - Axon bifurcation in regenerated nerves: Part II.

PMID- 16992953
TI  - The arrangement of nerve fibres in a regenerated nerve trunk.

PMID- 16992954
TI  - Fatty infiltration of the liver in hunger.

PMID- 16992956
TI  - The pressor principles of placental extracts.

PMID- 16992955
TI  - The mode of action of specific substances with special reference to secretin.

PMID- 16992957
TI  - Isolation of the pressor principles of putrid meat.

PMID- 16992958
TI  - On the nature of the fat contained in the liver, kidney and heart: Part II.

PMID- 16992959
TI  - A mammalian spinal preparation.

PMID- 16992961
TI  - The carbon monoxide capacity of reduced acid haematin.

PMID- 16992960
TI  - A stable derivative of haemochromogen.

PMID- 16992962
TI  - The causes of periodic or Cheyne-Stokes breathing.

PMID- 16992963
TI  - The regulation of normal breathing.

PMID- 16992964
TI  - The Coagulation of blood: Part II. The actions of snake venoms, peptone and leech
      extract.

PMID- 16992965
TI  - On degenerative changes in the nerve endings in striated muscle, in the nerve
      plexus on arteries, and in the nerve fibres of the frog.

PMID- 16992966
TI  - The "all or none" contraction of the amphibian skeletal muscle fibre.

PMID- 16992967
TI  - Experimental studies in the innervation of the skin.

PMID- 16992969
TI  - The electrical stimulation of muscle, as dependent upon the relative
      concentration of the calcium ions.

PMID- 16992970
TI  - The action of pressor amines produced by putrefaction.

PMID- 16992968
TI  - Separate mechanisms inside and outside the blood-brain barrier inducing metabolic
      changes in febrile rabbits.
AB  - 1. We investigated the acute phase response induced by either intravenous (I.V.)
      or intracerebroventricular injections of bacterial endotoxin or endogenous
      pyrogen. These caused either monophasic or biphasic fever, and the response
      includes changes in plasma concentration of iron, zinc, copper, fibrinogen and in
      circulating leucocyte count.2. The I.V. injection of a small dose of endotoxin or
      endogenous pyrogen produced a monophasic fever, while a large dose produced a
      biphasic fever. The ventricular injection of endogenous pyrogen produced a fever
      similar to the second phase of the biphasic fever.3. The I.V. injection of a
      small dose of endotoxin or endogenous pyrogen produced a low plasma zinc 8 h
      after injection, while the ventricular injection of endogenous pyrogen produced a
      low plasma zinc 24 h after injection. The I.V. injection of a large dose of
      endotoxin or endogenous pyrogen induced a low plasma zinc 8 and 24 h after
      injection, suggesting that the hypozincaemia induced by the large dose was
      mediated by both peripheral and central action of endogenous pyrogen with
      different time courses.4. The I.V. injection of the small dose did not affect the
      level of the plasma copper concentration but the I.V. injection of the large dose
      and the ventricular injection increased it 24 h after injection. It is considered
      that the plasma copper concentration is mainly controlled by the central action
      of endogenous pyrogen.5. The changes in the plasma iron and fibrinogen
      concentration and the circulating white blood cell count induced by the different
      doses and by the different routes showed very similar patterns, indicating that
      these are simultaneously controlled by both peripheral and central actions of
      endogenous pyrogen.6. The present results show that there are two separate
      mechanisms involved in the acute phase response, one inside and one outside the
      blood-brain barrier. From the consideration that endogenous pyrogen released from
      the phagocytic leucocytes induces fever and acute phase response by its action on
      both the peripheral target organs and the central nervous system, it is suggested
      that endogenous pyrogen acts both centrally and peripherally, in the same manner
      as other hormonal agents such as corticosteroids.

PMID- 16992971
TI  - The distribution of phosphoproteins in tissues: Part II.

PMID- 16992972
TI  - Metabolism in cystinuria.

PMID- 16992973
TI  - The dissociation curve of blood.

PMID- 16992974
TI  - The dissociation curve of haemoglobin.

PMID- 16992975
TI  - Physiological and histological observations on muscles chiefly in relation to the
      action of guanidine.

PMID- 16992977
TI  - The conditions of tissue respiration: Part III. The action of poisons.

PMID- 16992976
TI  - A metabolism experiment with special reference to the origin of uric acid.

PMID- 16992978
TI  - The influence of the visceral nerves upon the heart in cephalopods.

PMID- 16992980
TI  - On the unity of motor centres.

PMID- 16992979
TI  - On the relation between the electric disturbance in muscle and the propagation of
      the excited state.

PMID- 16992981
TI  - On the contraction of muscle, chiefly in relation to the presence of ;receptive'
      substances: Part IV. The effect of curari and of some other substances on the
      nicotine response of the sartorius and gastrocnemius muscles of the frog.

PMID- 16992982
TI  - On the estimation of purine bases in urine.

PMID- 16992983
TI  - The influence of carbohydrates and fats on protein metabolism.

PMID- 16992984
TI  - On the refractory period of muscle and nerve.

PMID- 16992985
TI  - The hexone bases from egg-white.

PMID- 16992986
TI  - Note on asphyxia in the spinal animal.

PMID- 16992987
TI  - The active principle of a Bini spear poison.

PMID- 16992988
TI  - The catalytic oxidation of guaiac resin by metallic copper.

PMID- 16992989
TI  - The mode of action of nicotine and curari, determined by the form of the
      contraction curve and the method of temperature coefficients.

PMID- 16992990
TI  - The effect of temperature on the dissociation curve of blood.

PMID- 16992992
TI  - Some new forms of apparatus for the analysis of the gases of the blood by the
      chemical method.

PMID- 16992991
TI  - Water rigor in frog's muscle.

PMID- 16992993
TI  - On the relation between the physical, chemical and electrical properties of the
      nerves: Part II. The tissues composing a nerve trunk.

PMID- 16992994
TI  - On the relation between the physical, chemical, and electrical properties of the
      nerves: Part III. Total ash, sulphates, phosphates.

PMID- 16992995
TI  - The nature of oxyhaemoglobin, with a note on its molecular weight.

PMID- 16992996
TI  - Improvements in the technique of blood-gas analysis.

PMID- 16992997
TI  - Contributions to the physiology of marine invertebrates: Part I.

PMID- 16992999
TI  - Quantitative researches on the summation of inadequate stimuli in muscle and
      nerve, with observations on the time-factor in electric excitation.

PMID- 16992998
TI  - The oxygen capacity of the blood after haemorrhage.

PMID- 16993000
TI  - Cardiac metabolism of alcohol.

PMID- 16993001
TI  - Creatin excretion in the bird and its significance.

PMID- 16993002
TI  - The gaseous metabolism of the small intestine: Part I. The gaseous exchanges
      during the absorption of water and dilute salt solutions.

PMID- 16993003
TI  - The gaseous metabolism of the small intestine: Part II. The gaseous exchanges
      during the absorption of Witte's peptone.

PMID- 16993004
TI  - A new mathematical treatment of changes of ionic concentration in muscle and
      nerve under the action of electric currents, with a theory as to their mode of
      excitation.

PMID- 16993005
TI  - An analysis of changes and differences in the excitatory process of nerves and
      muscles based on the physical theory of excitation.

PMID- 16993006
TI  - The delay of the electrical response of nerve to a second stimulus.

PMID- 16993007
TI  - The alleged formation of adrenine from tyrosine.

PMID- 16993009
TI  - The respiration of the tortoise heart in relation to functional activity.

PMID- 16993008
TI  - On the significance of carbon dioxide for the heart beat.

PMID- 16993010
TI  - Some colour reactions of adrenine and allied bases.

PMID- 16993012
TI  - The influence of oxygen inhalations on muscular work.

PMID- 16993011
TI  - The action of beryllium, lanthanum, yttrium and cerium on the frog's heart.

PMID- 16993013
TI  - A new form of blood-gas pump.

PMID- 16993014
TI  - The diastolic filling of the mammalian heart.

PMID- 16993015
TI  - The heat produced in contracture and muscular tone.

PMID- 16993016
TI  - On the "heat coagulation" of proteins.

PMID- 16993017
TI  - On the rhythmical contractility of the anal musculature of the crayfish and
      lobster.

PMID- 16993018
TI  - The question of haemolysis in the liver.

PMID- 16993019
TI  - The transformations in the fats in the hen's egg during development.

PMID- 16993020
TI  - Periodic breathing at high altitudes.

PMID- 16993021
TI  - The determination of the total oxygen capacity and blood volume at different
      altitudes by the carbon monoxide method.

PMID- 16993022
TI  - The action of tetrahydropapaveroline hydrochloride.

PMID- 16993023
TI  - The colour blind margin of the blind-spot, and the scotometer.

PMID- 16993024
TI  - A contribution to the study of muscle-enzymes.

PMID- 16993025
TI  - Fatty acid metabolism in the liver: Part I. A method of fatty-acid extraction.

PMID- 16993027
TI  - Flexion-reflex of the limb, crossed extension-reflex, and reflex stepping and
      standing.

PMID- 16993026
TI  - On the exhalation of drugs by the lungs.

PMID- 16993028
TI  - An inquiry into some chemical factors of fatigue.

PMID- 16993029
TI  - The influence of the presence and position of the various radicles of adrenalin
      on its physiological activity.

PMID- 16993030
TI  - The physiological action of beta-iminazolylethylamine.

PMID- 16993031
TI  - Contributions to physiological climatology: Part I. The relation of loss of water
      from the skin and lungs to the external temperature in actual climatic
      conditions.

PMID- 16993032
TI  - The influence of lactic acid upon the dissociation curve of blood.

PMID- 16993033
TI  - On the recovery of muscle and nerve after the passage of a propagated
      disturbance.

PMID- 16993034
TI  - On gastric sensation.

PMID- 16993035
TI  - The action of asphyxia upon the spinal animal.

PMID- 16993036
TI  - Observations on the sympathetic and sacral autonomic system of the frog.

PMID- 16993037
TI  - The origin and course of the vaso-motor fibres of the frog's foot.

PMID- 16993038
TI  - beta-Iminazolylethylamine a depressor constituent of intestinal mucosa.

PMID- 16993039
TI  - A reversed action of the vagus on the mammalian heart.

PMID- 16993040
TI  - Chemical structure and sympathomimetic action of amines.

PMID- 16993041
TI  - The gases of the arterial and venous blood of the cat.

PMID- 16993042
TI  - An investigation of the sino-auricular node of the mammalian heart.

PMID- 16993044
TI  - On the production of glycosuria in relation to the activity of the pancreas.

PMID- 16993043
TI  - The fate of parahydroxyphenylethylamine in the organism.

PMID- 16993045
TI  - The secretion of urine.

PMID- 16993046
TI  - On the governing influence of environment on enzymic action.

PMID- 16993047
TI  - The mode of union of certain poisons with cardiac muscle.

PMID- 16993048
TI  - The action of atropine, pilocarpine and physostigmine.

PMID- 16993050
TI  - Visual phenomena connected with the yellow spot.

PMID- 16993049
TI  - The composition of the gases of the blood in chloroform-anaesthesia.

PMID- 16993051
TI  - The influence of carbohydrate and fat on protein metabolism: II.-The effect of
      phloridzin glycosuria.

PMID- 16993052
TI  - The position occupied by the production of heat, in the chain of processes
      constituting a muscular contraction.

PMID- 16993054
TI  - On the alleged presence of an alcoholic enzyme in animal tissues and organs.

PMID- 16993053
TI  - The effect of altitude on the dissociation curve of blood.

PMID- 16993055
TI  - On the relation between the physical, chemical and electrical properties of the
      nerves: Part IV. Potassium, chlorine and potassium chloride.

PMID- 16993056
TI  - Some observations on the degeneration in the sympathetic and sacral autonomic
      nervous system of amphibia following nerve section.

PMID- 16993057
TI  - Some reactions of surviving arteries.

PMID- 16993058
TI  - The action of caffeine on muscle.

PMID- 16993059
TI  - Excitation and section of the auriculo-ventricular bundle.

PMID- 16993060
TI  - On the mode of production of lactose in the mammary gland.

PMID- 16993061
TI  - The pre-pyloric sphincter.

PMID- 16993063
TI  - On the replacement of calcium in certain neuro-muscular mechanisms by allied
      substances.

PMID- 16993062
TI  - A study of Bence-Jones protein, and of the metabolism in three cases of Bence
      Jones proteinuria.

PMID- 16993064
TI  - The thymus and sexual organs: III. Their relationship to the growth of the
      animal.

PMID- 16993065
TI  - The effects of asphyxia upon medullary centres: Part I. The vaso-motor centre.

PMID- 16993067
TI  - The action of tri-valent ions on living cells and on colloidal systems: II.
      Simple and complex kations.

PMID- 16993066
TI  - The direct determination of creatine in pathological urine.

PMID- 16993068
TI  - The diacetyl reaction for proteins.

PMID- 16993069
TI  - On the excitability of the respiratory centre.

PMID- 16993071
TI  - Chloroform and reversal of reflex effect.

PMID- 16993070
TI  - Observations on the role of potassium salts in frog's muscle.

PMID- 16993072
TI  - On the question of the identity of pepsin and rennet.

PMID- 16993074
TI  - Subjective and other phenomena connected with the retina.

PMID- 16993073
TI  - The quantitative estimation of the indophenol oxidase of animal tissues.

PMID- 16993075
TI  - Reflux from intestine to stomach.

PMID- 16993076
TI  - The influence of oxygen inhalation on the lactic acid produced during hard work.

PMID- 16993077
TI  - A method for estimating acetone in animal liquids.

PMID- 16993078
TI  - The effects of potassium salts upon the circulation and their action on plain
      muscle.

PMID- 16993079
TI  - On the relation of the refractory period to the propagated disturbance in nerve.

PMID- 16993080
TI  - The determination of the constants of the differential blood-gas apparatus.

PMID- 16993082
TI  - The relation between the physical, chemical and electrical properties of the
      nerves: Part V. The action of cinchonamine hydrochloride on frogs' nerves.

PMID- 16993081
TI  - On the "heat-coagulation" of proteins: Part II. The action of hot water upon egg
      albumen and the influence of acid and salts upon reaction velocity.

PMID- 16993083
TI  - The oxidation of isolated animal tissues.

PMID- 16993084
TI  - On the transference of the propagated disturbance from nerve to muscle with
      special reference to the apparent inhibition described by Wedensky.

PMID- 16993085
TI  - Observations on the effect of stimulation of the eighth and ninth spinal nerve
      roots, upon the bladder of the toad.

PMID- 16993086
TI  - The indophenol oxidase of mammalian and avian tissues.

PMID- 16993088
TI  - The effect of various poisons upon the response to nervous stimuli chiefly in
      relation to the bladder.

PMID- 16993087
TI  - The influence of tetrahydro-beta-naphthylamine upon the temperature and
      respiratory exchange.

PMID- 16993089
TI  - Further observations on the action of beta-iminazolylethylamine.

PMID- 16993090
TI  - Note on a reversed action of the chorda tympani on salivary secretion.

PMID- 16993091
TI  - Some recently elicited facts relating to carbohydrate metabolism and glycosuria.

PMID- 16993092
TI  - Observations on the localisation in the motor cortex of the baboon ("Papio
      anubis").

PMID- 16993093
TI  - The influence of acids upon the reduction of arterial blood.

PMID- 16993094
TI  - The relative rates of oxidation and reduction of blood.

PMID- 16993095
TI  - Protection of trypsin from destruction by heat.

PMID- 16993096
TI  - The total energy exchanges of intact cold-blooded animals at rest.

PMID- 16993097
TI  - On the chemical nature of the substance which cures polyneuritis in birds induced
      by a diet of polished rice.

PMID- 16993098
TI  - The nitrogen-content of blood.

PMID- 16993099
TI  - New determinations of certain absorption coefficients of importance in blood-gas
      investigations.

PMID- 16993100
TI  - A new absorptiometer.

PMID- 16993101
TI  - The absence of temperature changes during the transmission of a nervous impulse.

PMID- 16993102
TI  - On the preparation of secretin.

PMID- 16993104
TI  - Researches on the nature of enzyme action: II. The synthetic properties of anti
      emulsin.

PMID- 16993103
TI  - Contributions to the physiology of marine organisms: II. The influence of the
      carbon dioxide and oxygen tensions on rhythmical movements.

PMID- 16993105
TI  - On the relations to electrolytes of the hearts of different species of animals:
      I. Elasmobranchs and pecten.

PMID- 16993106
TI  - The influence of colloids on diuresis.

PMID- 16993108
TI  - The effect on blood-pressure of organ extracts.

PMID- 16993107
TI  - Observations on strychnine reversal.

PMID- 16993109
TI  - The male generative cycle in the hedgehog; with experiments on the functional
      correlation between the essential and accessory sexual organs.

PMID- 16993110
TI  - A new form of differential micro-calorimeter, for the estimation of heat
      production in physiological, bacteriological, or ferment actions.

PMID- 16993111
TI  - On the alleged formation of lactic acid in muscle during autolysis and in post
      survival periods.

PMID- 16993112
TI  - The innervation of the coronary vessels.

PMID- 16993113
TI  - The action of homologous alcohols and aldehydes on the tortoise heart.

PMID- 16993114
TI  - On the question of the presence in the frog of vaso-dilator fibres in the
      posterior roots of the nerves supplying the foot and in the sciatic nerve.

PMID- 16993115
TI  - The rule of reflex response in the limb reflexes of the mammal and its
      exceptions.

PMID- 16993117
TI  - The relation between oxidase and tissue respiration.

PMID- 16993116
TI  - Chemical nature of specific oxygen capacity in haemoglobin.

PMID- 16993118
TI  - The influence of increase of temperature upon the inhibitory mechanism of the
      heart of the frog.

PMID- 16993119
TI  - A short quantitative study of histozym, a tissue ferment.

PMID- 16993121
TI  - The action of the liver on the simpler sugars.

PMID- 16993120
TI  - The amyloclastic property of saliva.

PMID- 16993122
TI  - The influence of variations in temperature and blood-pressure on the performance
      of the isolated mammalian heart.

PMID- 16993123
TI  - A criticism of two methods for the determination of amyloclastic activity.

PMID- 16993124
TI  - On a mechanical method of correcting photographic records obtained from the
      capillary electrometer.

PMID- 16993125
TI  - The gaseous metabolism of striated muscle in warm-blooded animals: Part I.

PMID- 16993126
TI  - The relation of blood-flow to metabolism in the submaxillary gland.

PMID- 16993127
TI  - The preparation of the unconjugated acids of ox-bile.

PMID- 16993128
TI  - The laws of combination of haemoglobin with carbon monoxide and oxygen.

PMID- 16993129
TI  - The causes of absorption of oxygen by the lungs.

PMID- 16993130
TI  - On the question of an internal secretion from the human ovary.

PMID- 16993131
TI  - A spectroscopic method of estimating carbon monoxide.

PMID- 16993132
TI  - The action of various conditions on carbon monoxide haemoglobin.

PMID- 16993133
TI  - Heat coagulation of haemoglobin compounds.

PMID- 16993134
TI  - On creatin-destroying bacilli in the intestine, and their isolation.

PMID- 16993135
TI  - The effect of a diet of polished rice on the nitrogen and phosphorus of the
      brain.

PMID- 16993136
TI  - The effect of inhalation of oxygen on the rate of the pulse in health.

PMID- 16993137
TI  - The distribution and physiological action of the suprarenal medullary tissue in
      petromyzon fluviatilis.

PMID- 16993138
TI  - On the summation of propagated disturbances in nerve and muscle.

PMID- 16993139
TI  - The gaseous metabolism of the submaxillary gland with reference especially to the
      effect of adrenalin and the time relation of the stimulus to the oxidation
      process.

PMID- 16993140
TI  - The control of the suprarenal glands by the splanchnic nerves.

PMID- 16993142
TI  - The actions of pituitrin, adrenalin and barium on the circulation of the bird.

PMID- 16993141
TI  - On the use of the decapitated duck in physiological investigations.

PMID- 16993143
TI  - Feeding experiments illustrating the importance of accessory factors in normal
      dietaries.

PMID- 16993145
TI  - The heat-producton of surviving amphibian muscles, during rest, activity, and
      rigor.

PMID- 16993144
TI  - Note on the fate of secretin in pancreatic diabetes.

PMID- 16993146
TI  - The anti-coagulants in blood and serum.

PMID- 16993147
TI  - Experiments on the consumption of sugar in the normal and the diabetic heart.

PMID- 16993148
TI  - On a simple form of stromuhr.

PMID- 16993149
TI  - Experiments on the oxygen secretion in the lung of man by the carbon monoxide
      method.

PMID- 16993150
TI  - The comparative osmotic pressure of the blood and of the urine, during diuresis
      caused by Ringer's fluid.

PMID- 16993151
TI  - The oxygen exchange of the suprarenal gland.

PMID- 16993152
TI  - The function of lipoids in tissue respiration and in the activity of oxidases.

PMID- 16993153
TI  - The gaseous metabolism of the heart and lungs.

PMID- 16993154
TI  - The capacity of the air passages under varying physiological conditions.

PMID- 16993155
TI  - Observations on vascular reflexes chiefly in relation to the effect of
      strychnine.

PMID- 16993156
TI  - On the "heat coagulation" of proteins: Part IV. The conditions controlling the
      agglutination of proteins already acted upon by hot water.

PMID- 16993157
TI  - The gaseous metabolism of the liver: Part I. In fasting and late digestion.

PMID- 16993158
TI  - On the part played by the suprarenals in the normal vascular reactions of the
      body.

PMID- 16993159
TI  - On local vascular reactions and their interpretation.

PMID- 16993160
TI  - Absence of apnoea after forced breathing.

PMID- 16993161
TI  - The action of carbon dioxide on the vascular system.

PMID- 16993162
TI  - The coagulation of milk by rennin.

PMID- 16993163
TI  - Fatty acid metabolism in the liver: II. The relation of the fatty acids in the
      food of plaice to those in their livers and myotomes.

PMID- 16993165
TI  - On the conduction of subnormal disturbances in normal nerve.

PMID- 16993164
TI  - The ferments of the pancreas: Part I. The generation of trypsin from trypsinogen
      by enterokinase.

PMID- 16993166
TI  - Broncho-dilator nerves.

PMID- 16993167
TI  - Observations on the effects of muscular exercise upon man.

PMID- 16993168
TI  - On the secretion of pancreatic juice.

PMID- 16993169
TI  - On depressor nerve fibres in the vagus of the frog.

PMID- 16993170
TI  - The utilisation of different sugars by the normal heart.

PMID- 16993171
TI  - The behaviour of the diabetic heart towards sugar.

PMID- 16993172
TI  - Afferent impressions from the respiratory mechanism.

PMID- 16993173
TI  - The oxygen capacity of blood considered in relation to the concentration of
      haemoglobin.

PMID- 16993174
TI  - Further experimental studies on beri-beri. The action of certain purine- and
      pyrimidine-derivatives.

PMID- 16993176
TI  - The significance of the suprarenal capsules in the action of certain alkaloids.

PMID- 16993175
TI  - Determination of the constant of the differential blood gas apparatus, with a
      note on the specific oxygen capacity of blood.

PMID- 16993177
TI  - On the extrinsic nerves of the heart of the bird.

PMID- 16993178
TI  - The liver in relation to creatine metabolism in the bird.

PMID- 16993179
TI  - Some experiments on the precipitation of suspensoid protein by various ions and
      some suggestions as to its cause.

PMID- 16993180
TI  - The influence of lack of oxygen on tissue respiration.

PMID- 16993181
TI  - On the presence of beta-imidazolethylamine in the intestinal wall; with a method
      of isolating a bacillus from the alimentary canal which converts histidine into
      this substance.

PMID- 16993183
TI  - New visual phenomena.

PMID- 16993182
TI  - On the "heat coagulation" of proteins: Part III. The influence of alkali upon
      reaction velocity.

PMID- 16993184
TI  - The preparation from yeast and certain foodstuffs of the substance the deficiency
      of which in diet occasions polyneuritis in birds.

PMID- 16993185
TI  - Observations upon the effects of section of the spinal cord upon temperature and
      metabolism.

PMID- 16993186
TI  - State-dependent radial elasticity of attached cross-bridges in single skinned
      fibres of rabbit psoas muscle.
AB  - 1. In a single skinned fibre of rabbit psoas muscle, upon attachment of cross
      bridges to actin in the presence of ADP or pyrophosphate (PP(i)), the separation
      between the contractile filaments, as determined by equatorial X-ray diffraction,
      is found to decrease, suggesting that force is generated in the radial
      direction.2. The single muscle fibres were subjected to compression by 0-8% of
      dextran T(500). The changes in lattice spacings by dextran compression were
      compared with changes induced by cross-bridge attachment to actin. Based on this
      comparison, the magnitude and the direction of the radial force generated by the
      attached cross-bridges were estimated. The radial cross-bridge force varied with
      filament separation, and the magnitude of the radial cross-bridge force reached
      as high as the maximal axial force produced during isometric contraction.3. One
      key parameter of the radial elasticity, i.e. the equilibrium spacing where the
      radial force is zero, was found to depend on the ligand bound to the myosin head.
      In the presence of ADP, the equilibrium spacing was 36 nm. In the presence of
      MgPP(i) the equilibrium spacing shifted to 35 nm and Ca(2+) had little effect on
      the equilibrium spacing.4. The equilibrium spacing was independent of the
      fraction of cross-bridges attached to actin. The fraction of cross-bridges
      attached in rigor was modulated from 100% to close to 0% by adding up to 10 mM of
      ATPgammaS in the rigor solution. The lattice spacing remained at 38 nm, the
      equilibrium spacing for nucleotide-free cross-bridges at mu = 170 mM.5. Radial
      force generated by cross-bridges in rigor at large lattice spacings (38 nm </=
      d(10) </= 46 nm) appeared to vary linearly with lattice spacing.6. The titration
      of ATPgammaS to fibres in rigor provided a correlation between the radial
      stiffness of the nucleotide-free cross-bridges and the equatorial intensities.
      The relation between the equatorial intensity ratio I(11)/I(10) and radial
      stiffness appeared to be approximately linear.7. The fibres under different
      conditions showed a wide range of radial stiffness, which was not proportional to
      the apparent axial stiffness of the fibre. If the apparent axial stiffness is a
      measure of the fraction of cross-bridges bound to actin, it follows that the
      radial elastic constant is state dependent; or vice versa.8. Differences in
      equilibrium lattice spacing and in radial elastic constant, most probably reflect
      differences in the molecular structure of the acto-myosin complex and there is
      more than one single conformation of the various strongly bound cross-bridge
      states.9. Determining equilibrium spacings of the radial elasticity appears to be
      an effective new approach in detecting structural differences among the attached
      cross-bridges, since this approach is independent of the fraction of cross
      bridges attached, a factor that frequently encumbers the interpretation of
      structural studies of attached cross-bridge states.

PMID- 16993187
TI  - On the summation of contractions.

PMID- 16993188
TI  - The energy degraded in the recovery processes of stimulated muscles.

PMID- 16993189
TI  - The reaction between metallic salts and the soluble carbonates and its bearing
      upon the precipitation of protein.

PMID- 16993190
TI  - On the action of electrolytes on paramoecium.

PMID- 16993191
TI  - Distribution of nerves in the heart.

PMID- 16993192
TI  - Action of certain drugs on isolated strips of ventricle.

PMID- 16993194
TI  - Calorimetrical experiments on warm-blooded animals.

PMID- 16993193
TI  - The ferments of the pancreas: Part II. The action of calcium salts in the
      generation of trypsin from trypsinogen.

PMID- 16993195
TI  - Studies on beri-beri: VII. Chemistry of the vitamine-fraction from yeast and rice
      polishings.

PMID- 16993196
TI  - The after-images of black and white on coloured surfaces.

PMID- 16993197
TI  - The aberrant radial artery and Valsalva's experiment.

PMID- 16993198
TI  - On functional analysis by the action of electrolytes.

PMID- 16993199
TI  - Researches on the nature of enzyme action: III. The synthetic action of enzymes.

PMID- 16993200
TI  - On the influence of preliminary heating upon peptic and tryptic proteolysis.

PMID- 16993201
TI  - The innervation of the adrenal glands.

PMID- 16993203
TI  - The part played by the lungs in the oxidative processes of the body.

PMID- 16993202
TI  - On the action of ergotoxine; with special reference to the existence of
      sympathetic vasodilators.

PMID- 16993205
TI  - The effect of alcohol on the excitation, conduction and recovery processes in
      nerve.

PMID- 16993204
TI  - The absolute mechanical efficiency of the contraction of an isolated muscle.

PMID- 16993206
TI  - An apparatus for perfusing the mammalian heart.

PMID- 16993207
TI  - The response of the respiratory centre to carbonic acid, oxygen, and hydrogen ion
      concentration.

PMID- 16993208
TI  - The influence of nerve stimulation on the electrocardiogram.

PMID- 16993209
TI  - Study of the respiratory mechanism in the duck.

PMID- 16993210
TI  - On dynamic equilibrium in the heart.

PMID- 16993211
TI  - Wedensky inhibition in relation to the ;all-or-none' principle in nerve.

PMID- 16993212
TI  - On the real nature of the so-called artificial globulin.

PMID- 16993213
TI  - The protracted contraction of muscle caused by nicotine and other substances
      chiefly in relation to the rectus abdominis muscle of the frog.

PMID- 16993214
TI  - Further observations on the production of reflex stepping by combination of
      reflex excitation with reflex inhibition.

PMID- 16993215
TI  - The cerebro-spinal fluid: I. Secretion of the fluid.

PMID- 16993216
TI  - The heat production of fatigue and its relation to the production of lactic acid
      in amphibian muscle.

PMID- 16993217
TI  - A simple method of calibrating the differential blood gas apparatus.

PMID- 16993219
TI  - Further experiments on the action of the vagus on the electrogram of the frog's
      heart.

PMID- 16993218
TI  - The effect of glucose on the gaseous metabolism of the isolated mammalian heart.

PMID- 16993220
TI  - On the average composition of the alveolar air and its variations during the
      respiratory cycle.

PMID- 16993222
TI  - The all-or-none principle in nerve.

PMID- 16993221
TI  - The effect of adrenalin on the gaseous metabolism of the isolated mammalian
      heart.

PMID- 16993223
TI  - Studies on beriberi: VIII. The relationship of beriberi to glands of internal
      secretion.

PMID- 16993225
TI  - Note on the pigment of a Bermuda nudibranch, Chromodoris zebra Heilprin.

PMID- 16993224
TI  - The effect of thymus feeding on the activity of the reproductive organs in the
      rat.

PMID- 16993226
TI  - Hydrogen ion concentrations limiting automaticity in different regions of the
      frog's heart.

PMID- 16993227
TI  - On the production and utilisation of glycogen in normal and diabetic animals.

PMID- 16993228
TI  - Note on differences in electrical potential within the living cell.

PMID- 16993229
TI  - The regulation of respiration and circulation during the initial stages of
      muscular work.

PMID- 16993230
TI  - The carbohydrate metabolism of the isolated heart lung preparation.

PMID- 16993231
TI  - The changes in the reaction of growing organisms to narcotics.

PMID- 16993232
TI  - The volume of the "dead space" in breathing.

PMID- 16993233
TI  - The nature of thrombin and anti-thrombin.

PMID- 16993234
TI  - The ileo-caecal sphincter.

PMID- 16993235
TI  - The normal movements of the colon in man.

PMID- 16993236
TI  - The action of ions and lipoids upon the frog's heart.

PMID- 16993237
TI  - A note on some factors which determine the blood-flow through the coronary
      circulation.

PMID- 16993239
TI  - The heat-production in prolonged contractions of an isolated frog's muscle.

PMID- 16993238
TI  - Experiments on the pulmonary circulation.

PMID- 16993240
TI  - The auto-catalysis of trypsinogen.

PMID- 16993241
TI  - The ferments of the pancreas: Part III. The properties of trypsin, trypsinogen
      and enterokinase.

PMID- 16993242
TI  - Lactic acid formation, survival respiration and rigor mortis in mammalian muscle.

PMID- 16993243
TI  - The sugar consumption in the surviving normal and diabetic heart.

PMID- 16993244
TI  - Studies on pellagra: I. The influence of the milling of maize on the chemical
      composition and the nutritive value of maize-meal.

PMID- 16993245
TI  - The influence of carbon dioxide on the heart in varying degrees of anaesthesia.

PMID- 16993246
TI  - Diuresis.

PMID- 16993247
TI  - On the nature of the fundamental activity of the nervous centres; together with
      an analysis of the conditioning of rhythmic activity in progression, and a theory
      of the evolution of function in the nervous system.

PMID- 16993248
TI  - Hyperpnoea as a result of pain and ether in man.

PMID- 16993250
TI  - The antagonism of curari and nicotine in skeletal muscle.

PMID- 16993249
TI  - The relation between the size of the propagated disturbance and the rate of
      conduction in nerve.

PMID- 16993251
TI  - The formation of urine in the frog.

PMID- 16993253
TI  - The influence of distention of the lungs on human respiration.

PMID- 16993252
TI  - The absorption and dissociation of carbon dioxide by human blood.

PMID- 16993254
TI  - The heart, lung, kidney preparation.

PMID- 16993255
TI  - The ferments of the pancreas: Part IV. Steapsin.

PMID- 16993257
TI  - Cerebro-spinal fluid: III. The general effects of increasing the cerebro-spinal
      pressure.

PMID- 16993256
TI  - The sensitiveness of the respiratory centre to carbonic acid, and the dead space
      during hyperpnoea.

PMID- 16993258
TI  - The influence of a vitamine-free diet on the carbohydrate metabolism.

PMID- 16993259
TI  - On some cardiac reflexes.

PMID- 16993260
TI  - The determination of lactic acid.

PMID- 16993262
TI  - On the mechanical factors which determine the output of the ventricles.

PMID- 16993261
TI  - On the constancy of the systolic output under varying conditions.

PMID- 16993263
TI  - The time relations of acid production in muscle during contraction.

PMID- 16993265
TI  - Myothermic experiments in salt-solutions in relation to the various stages of a
      muscular contraction.

PMID- 16993264
TI  - On the origin of the "c" wave in the jugular pulse.

PMID- 16993266
TI  - Gaseous exchange in the decerebrate animal.

PMID- 16993267
TI  - The suprarenal bodies and diuresis.

PMID- 16993268
TI  - The temperature coefficient of the refractory period in nerve.

PMID- 16993269
TI  - The regulation of the heart beat.

PMID- 16993270
TI  - Further observations on the constricting action of adrenaline on the cerebral
      vessels.

PMID- 16993271
TI  - The influence of carbohydrate and fat on protein metabolism: III. The effect of
      sodium selenite.

PMID- 16993272
TI  - The cerebro-spinal fluid: II. Cerebro-spinal pressure.

PMID- 16993274
TI  - On the effects of complete and incomplete castration upon horn growth in herdwick
      sheep.

PMID- 16993273
TI  - Vaso-motor nerves in the lungs.

PMID- 16993275
TI  - The carbon dioxide production of heat rigor in muscle, and the theory of intra
      molecular oxygen.

PMID- 16993276
TI  - Observations upon decerebrate rigidity.

PMID- 16993277
TI  - Is polished rice plus vitamine a complete food?

PMID- 16993278
TI  - Single cell RT-PCR reaches out to the NMDA receptor.

PMID- 16993279
TI  - The influence of temperature on the secretion of sweat.

PMID- 16993281
TI  - Contributions to physiological climatology: Part II.

PMID- 16993280
TI  - Observations on anaesthesia by phenyl-ethyl malonyl urea.

PMID- 16993282
TI  - On the alleged influence of adrenaline and of the sympathetic nervous system on
      the tonus of skeletal muscle.

PMID- 16993283
TI  - On the reciprocal innervation in tonic reflexes from the labyrinths and the neck.

PMID- 16993284
TI  - Fatty acid metabolism in the liver: IV. The relation of the iodine values of
      mesenteric and kidney fatty acids to those of liver fatty acids in pregnant and
      lactating rabbits.

PMID- 16993285
TI  - On saline diuresis.

PMID- 16993286
TI  - The fate of fatty acids in the survival processes of muscle.

PMID- 16993287
TI  - On the occurrence of a plastic flexor tone in the monkey.

PMID- 16993288
TI  - On the effect of artificial stimulation of the red nucleus in the anthropoid ape.

PMID- 16993290
TI  - On the activities of the central nervous system of the un-born foetus of the cat;
      with a discussion of the question whether progression (walking, etc.) is a
      "learnt" complex.

PMID- 16993289
TI  - Note on the physiology of the basal ganglia and mid-brain of the anthropoid ape,
      especially in reference to the act of laughter.

PMID- 16993291
TI  - The action of serum on the lipase of pancreatic juice.

PMID- 16993292
TI  - Observations upon the body temperature of Europeans living in the tropics.

PMID- 16993294
TI  - The ferments of the pancreas: Part V. The carbohydrate ferments of pancreatic
      juice.

PMID- 16993293
TI  - The mechanical regulation of the heart beat in the tortoise.

PMID- 16993295
TI  - The simple character of the yellow sensation.

PMID- 16993296
TI  - The diffusion of gases through the lungs of man.

PMID- 16993298
TI  - The influence of veratrin poisoning on the electrogram of the frogs' hearts.

PMID- 16993297
TI  - The mode of action of carbon dioxide on the blood-pressure.

PMID- 16993299
TI  - Observations on reflex responses to single break-shocks.

PMID- 16993300
TI  - The eosinophil cell of teleostean fish.

PMID- 16993301
TI  - On pituitary secretion.

PMID- 16993302
TI  - The effect of various mechanical conditions on the gaseous metabolism and
      efficiency of the mammalian heart.

PMID- 16993304
TI  - The physiological action of physostigmine and its action on denervated skeletal
      muscle.

PMID- 16993303
TI  - An apparatus for projecting spectra.

PMID- 16993305
TI  - The rate of loss of weight in skeletal muscle after nerve section with some
      observations on the effect of stimulation and other treatment.

PMID- 16993306
TI  - Diuresis-the pituitary factor.

PMID- 16993307
TI  - The affinities of haematin.

PMID- 16993308
TI  - On the secretion of bile.

PMID- 16993309
TI  - The action of pituitrin on the secretion of milk.

PMID- 16993310
TI  - The influence of the vagus on pancreatic secretion.

PMID- 16993311
TI  - The relation of length to tension development and heat production on contraction
      in muscle.

PMID- 16993312
TI  - On the ovarian factor concerned in the recurrence of the oestrous cycle.

PMID- 16993313
TI  - Fatty acid metabolism in the liver: III. Fatty acid infiltration of the liver
      during pregnancy and lactation.

PMID- 16993314
TI  - The afferent fibres of the abdominal vagus in the rabbit and cat.

PMID- 16993315
TI  - Some results of excision of the adrenal glands.

PMID- 16993316
TI  - The relation between successive responses of the ventricle to electric stimuli
      and ventricular fibrillation.

PMID- 16993317
TI  - The respiratory exchanges of the heart in the diabetic animal.

PMID- 16993318
TI  - The estimation of non-protein nitrogen and urea nitrogen in blood.

PMID- 16993319
TI  - The metabolism of the salivary gland: I. The nitrogen metabolism of the resting
      gland.

PMID- 16993321
TI  - A method of bringing a small quantity of blood into equilibrium with a given gas.
      "Microaerotonometer.".

PMID- 16993320
TI  - The significance of the pericardium.

PMID- 16993322
TI  - On the contractile movement of the gall-bladder.

PMID- 16993323
TI  - Interest as a factor in antagonism and simultaneous contrast.

PMID- 16993324
TI  - An improved spectrophotometer.

PMID- 16993325
TI  - On the reaction of bile.

PMID- 16993327
TI  - The effect of isotonic Ringer solution on blood corpuscles.

PMID- 16993326
TI  - The action of barium chloride on the vascular system. A contribution to the study
      of the antagonistic action of nicotine and curare.

PMID- 16993328
TI  - Contributions to the physiology of the pulmonary circulation.

PMID- 16993329
TI  - Note on vagus stimulation of the adrenalised heart.

PMID- 16993330
TI  - The influence of venous filling upon the rate of the heart.

PMID- 16993331
TI  - Researches on the nature of enzyme action: IV. The action of insoluble enzymes.

PMID- 16993332
TI  - Physiological aspect of photographic safe light screens.

PMID- 16993333
TI  - The mechanism of fluid absorption from tissue spaces.

PMID- 16993334
TI  - Glycolysis in diabetic blood with a method for the estimation of blood sugar.

PMID- 16993335
TI  - Studies in calcium metabolism: I. The deposition of lime salts in the integument
      of decapod crustacea.

PMID- 16993336
TI  - Observations on the nerve endings, receptive substance and contractile substance
      of muscle.

PMID- 16993337
TI  - The cerebro-spinal fluid: IV. Circulation.

PMID- 16993338
TI  - Some experiments on antagonism between certain drugs.

PMID- 16993339
TI  - Sketch of the progress of discovery in the eighteenth century as regards the
      autonomic nervous system.

PMID- 16993340
TI  - Uterine contractions and ovarian extract.

PMID- 16993341
TI  - On anaphylactic effects as shown in perfusion experiments on the excised heart.

PMID- 16993342
TI  - Variations in the blood sugar in health.

PMID- 16993343
TI  - The regulation of excretion of water by the kidneys: I.

PMID- 16993344
TI  - The regulation of excretion of water by the kidneys: II.

PMID- 16993345
TI  - Lactic acid metabolism in the isolated heart (heart lung preparation).

PMID- 16993346
TI  - On the biochemical mechanism of growth.

PMID- 16993347
TI  - Observations on denervated muscle.

PMID- 16993348
TI  - The recovery of conductivity and of excitability in nerve.

PMID- 16993349
TI  - Observations upon the growth of tissues in vitro relating to the origin of the
      heart beat.

PMID- 16993350
TI  - The function of haemoglobin in invertebrates with special reference to planorbis
      and chironomus larvae.

PMID- 16993351
TI  - Fatty infiltration of the cat's kidney.

PMID- 16993352
TI  - The effect on higher animals of the sterilization of the inhabited medium, the
      air and the food.

PMID- 16993353
TI  - Speech without using the larynx.

PMID- 16993354
TI  - Slow waves of contraction in muscle.

PMID- 16993355
TI  - The action of sodium sulphocyanide on muscle.

PMID- 16993356
TI  - The influence of the vagus on pancreatic secretion: Second communication.

PMID- 16993358
TI  - The direct and indirect effects of X-rays on the thymus gland and reproductive
      organs of white rats.

PMID- 16993357
TI  - The structure of the thymus gland and of the reproductive organs in white rats.
      Together with some observations on the breeding capacity of these animals.

PMID- 16993359
TI  - The metabolism of arginine.

PMID- 16993360
TI  - On the amount of blood in the lungs.

PMID- 16993361
TI  - The action of guanidine on the neuro-myal system of decapod crustacea.

PMID- 16993362
TI  - On the capacity of blood and haemoglobin to unite with carbon dioxide.

PMID- 16993363
TI  - Calcium and the action of certain drugs upon the frog's heart.

PMID- 16993364
TI  - A comparison between voluntary and electrically induced muscular work in man.

PMID- 16993365
TI  - The oxygen use of denervated muscle.

PMID- 16993366
TI  - The metabolism of arginine.

PMID- 16993367
TI  - Observations on denervated and on regenerating muscle.

PMID- 16993368
TI  - The rate of formation of fibrin ferment from prothrombin by the action of
      thrombokinase and calcium chloride.

PMID- 16993369
TI  - Reflexes elicitable in the cat from pinna vibrissae and jaws.

PMID- 16993371
TI  - On the reaction of the blood in the body.

PMID- 16993370
TI  - X-acid as a remedy in polyneuritis and beri-beri.

PMID- 16993372
TI  - Some actions of adrenalin upon the liver.

PMID- 16993373
TI  - On summation of propagated disturbances in the claw of astacus, and on the double
      neuro-muscular system of the adductor.

PMID- 16993374
TI  - The relations of carbon dioxide in the blood.

PMID- 16993375
TI  - The excretion of urea and sugar by the kidney.

PMID- 16993376
TI  - On the localisation of the calcium and potassium salts concerned in the mediation
      of the action of the vagus nerve on the heart of the frog.

PMID- 16993377
TI  - Some observations on the action of guanidine on frog's muscle.

PMID- 16993378
TI  - The volume of the dead space in breathing and the mixing of gases in the lungs of
      man.

PMID- 16993380
TI  - The influence of the respiration on the exchange of SO(4) between corpuscles and
      plasma and its effect on the excretion of SO(4).

PMID- 16993379
TI  - The mechanism of cardiac acceleration by warmth and by adrenalin.

PMID- 16993381
TI  - The mechanical effect of fluid in the pericardium on the function of the heart.

PMID- 16993382
TI  - The nutritive value of margarines and butter substitutes with reference to their
      content of the fat-soluble accessory growth substance.

PMID- 16993383
TI  - Preparation of strong solutions of haemoglobin and of colour filters of
      haemoglobin compounds.

PMID- 16993384
TI  - The reaction regulator mechanism of the blood before and after haemorrhage.

PMID- 16993385
TI  - On the internal secretion of the sexual glands.

PMID- 16993386
TI  - Sodium citrate and the action of certain drugs upon the frog's heart.

PMID- 16993387
TI  - The calcium and phosphorus of the blood and a suggestion as to the nature of the
      act of coagulation.

PMID- 16993389
TI  - The guanidin content of muscle in tetania parathyreopriva.

PMID- 16993388
TI  - On the suture of separate nerve bundles in a nerve trunk and on internal nerve
      plexuses.

PMID- 16993390
TI  - Observations on the atrophy of denervated muscle.

PMID- 16993391
TI  - The velocity factor in cardiac work.

PMID- 16993392
TI  - On the creatin content of skeletal muscle in degeneration following denervation.

PMID- 16993393
TI  - Chromatic aberration and resolving power of the eye.

PMID- 16993394
TI  - On the stimulation and paralysis of nerve cells and nerve endings: Part II.
      Paralysis by curari, strychnine and brucine and its antagonism by nicotine.

PMID- 16993395
TI  - The control of the physical regulation of the body temperature.

PMID- 16993396
TI  - The spectrocomparator, an apparatus designed for the determination of the
      percentage saturation of blood with oxygen or carbon monoxide.

PMID- 16993397
TI  - The respiratory function of the blood in fishes.

PMID- 16993398
TI  - Adrenalin and pituitrin-a study in interaction and interrelation.

PMID- 16993399
TI  - Some further observations on blood reaction.

PMID- 16993400
TI  - Fats and fatty acids as food.

PMID- 16993401
TI  - A contribution to the physiology of the aqueous humour.

PMID- 16993402
TI  - A simple method of short-circuiting the portal circulation.

PMID- 16993403
TI  - Histamine shock.

PMID- 16993404
TI  - The rate of diffusion of gases through animal tissues, with some remarks on the
      coefficient of invasion.

PMID- 16993406
TI  - Influence of saprophyte bacteria on oxidation in higher animals: 5th series of
      experiments.

PMID- 16993405
TI  - The number and distribution of capillaries in muscles with calculations of the
      oxygen pressure head necessary for supplying the tissue.

PMID- 16993407
TI  - The respiratory response to anoxaemia.

PMID- 16993408
TI  - The effects of shallow breathing.

PMID- 16993409
TI  - The physiological action of extracts of the electrical organs of the skate (Raia
      clavata) and torpedo (T. marmorata).

PMID- 16993410
TI  - The supply of oxygen to the tissues and the regulation of the capillary
      circulation.

PMID- 16993411
TI  - The vasodilator action of histamine and of some other substances.

PMID- 16993412
TI  - The distribution of blood, glycogen and fat in the lobes of the liver.

PMID- 16993413
TI  - On the possibility of mixing the air in the lungs with foreign air, especially as
      it is used in Krogh and Lindhard's nitrous oxide method.

PMID- 16993414
TI  - The effect of thyro-parathyroidectomy on the heart and circulation.

PMID- 16993415
TI  - The nutritive value of certain fish.

PMID- 16993416
TI  - On physiological radio-activity.

PMID- 16993417
TI  - Studies in the regeneration of denervated mammalian muscle: III. Effects of
      massage and electrical treatment.

PMID- 16993418
TI  - The relation of the animal cell to electrolytes: I. A physiological study of the
      egg of the trout.

PMID- 16993419
TI  - The time relations of the blood-pressure changes after excision of the adrenal
      glands, with some observations on blood volume changes.

PMID- 16993420
TI  - The reaction and carbon dioxide carrying power of blood-a mathematical treatment:
      Part II.

PMID- 16993421
TI  - The influence of the state of the blood on the interworking of the eyes.

PMID- 16993422
TI  - Pitch discrimination in the dog.

PMID- 16993423
TI  - The effect of thyro-parathyreoidectomy on the heart and circulation: Part II.
      Action of guanidin on the heart of the frog.

PMID- 16993424
TI  - The colloid-free filtrate of serum.

PMID- 16993425
TI  - Studies on the capillariometer mechanism: I. The reaction to stimuli and the
      innervation of the blood vessels in the tongue of the frog.

PMID- 16993426
TI  - The determination of the circulation rate in man from the arterial and venous
      CO(2)-tension and the CO(2)-output.

PMID- 16993427
TI  - The changes in respiration at the transition from work to rest.

PMID- 16993428
TI  - The effect of injection of guanidin on the creatin-content of muscle.

PMID- 16993429
TI  - Non-medullated fibres in the spinal ganglia.

PMID- 16993430
TI  - The flow of oxygen through the pulmonary epithelium.

PMID- 16993431
TI  - The cortical paths for mastication and deglutition.

PMID- 16993432
TI  - The influence of the nervous system on glycaemia and glycosuria.

PMID- 16993433
TI  - Studies in the regeneration of denervated mammalian muscle: II. Effect of
      massage.

PMID- 16993434
TI  - A simple photographic method of registering vertical movements on a horizontal
      plane.

PMID- 16993435
TI  - Vaso-motor centres: Part I. Effect of strychnine on blood-pressure in the spinal
      animal.

PMID- 16993436
TI  - Neuroglia and non-myelinated fibres in nerves.

PMID- 16993437
TI  - Acquired tolerance for alcohol in the frog's heart.

PMID- 16993438
TI  - Observations on cyanide anoxaemia.

PMID- 16993439
TI  - The reaction and carbon dioxide carrying power of blood-a mathematical treatment:
      Part I.

PMID- 16993440
TI  - The response to respiratory resistance.

PMID- 16993442
TI  - A study of the seasonal changes in avian testes.

PMID- 16993441
TI  - The response of human sensory nerves to currents of short duration.

PMID- 16993443
TI  - Studies in the regeneration of denervated mammalian muscle: I. Volume changes and
      temperature changes.

PMID- 16993444
TI  - Vaso-motor centres: Part II. Observations on the action of strychnine.

PMID- 16993445
TI  - The neutrality of the blood.

PMID- 16993446
TI  - Experiments on acclimatisation to reduced atmospheric pressure.

PMID- 16993447
TI  - The thymus and tetany.

PMID- 16993448
TI  - The hyperglycaemia of asphyxia and the part played therein by the suprarenals.

PMID- 16993449
TI  - Carbohydrate metabolism in ducks.

PMID- 16993450
TI  - Action of substances, influencing the carbohydrate metabolism, in experimental
      beri-beri.

PMID- 16993452
TI  - Note on the permeability of red corpuscles for glucoses and glucosamine.

PMID- 16993451
TI  - Experiments on the internal secretion of the sexual glands, especially on
      experimental hermaphroditism.

PMID- 16993453
TI  - A simple definite test for ascertaining the existence of functional cardiac
      calcium.

PMID- 16993454
TI  - The partition of CO(2) between plasma and corpuscles in oxygenated and reduced
      blood.

PMID- 16993455
TI  - The relation of oxyhaemoglobin to the CO(2) of the blood.

PMID- 16993456
TI  - Colorimetric determination of the reaction of blood by dialysis.

PMID- 16993457
TI  - The carbon dioxide carrying power of the constituents of plasma. The alkali
      reserve of blood.

PMID- 16993458
TI  - The relation between respiration and the pulse-rate.

PMID- 16993459
TI  - The influence of venous pressure upon the heart-rate.

PMID- 16993460
TI  - On the correlation of the rate of heart beat, breathing, bodily movement and
      sensory stimuli.

PMID- 16993461
TI  - Studies on muscular contraction: I. The influence of temperature on the
      mechanical performance of skeletal and heart muscle.

PMID- 16993462
TI  - On the existence of antidromic fibres in the frog and their influence on the
      capillaries.

PMID- 16993463
TI  - On the permeability of epithelial layer of the bladder to water and salt.

PMID- 16993464
TI  - The ear as morphologically an apparatus for perceiving depth below sea-level.

PMID- 16993465
TI  - Cardiac tetanus.

PMID- 16993466
TI  - Nitrite methaemoglobin and related pigments.

PMID- 16993467
TI  - Variations in the resistance of protozoon organisms to toxic agents.

PMID- 16993468
TI  - The action of certain serum constituents upon the heart and plain muscle.

PMID- 16993470
TI  - The use of thermionic valves with the string galvanometer.

PMID- 16993469
TI  - The effect of alterations of temperature upon the functions of the isolated
      heart.

PMID- 16993471
TI  - Physical exertion, fitness and breathing.

PMID- 16993472
TI  - The recovery process of excitable tissues: Part I.

PMID- 16993473
TI  - Experiments on the regulation of the blood's alkalinity: I.

PMID- 16993475
TI  - The avoidance of objects by bats in their flight.

PMID- 16993474
TI  - The muscular mechanism of the diaphragm.

PMID- 16993476
TI  - The action of the HCO(3) ion and of morphine on the respiratory centre.

PMID- 16993477
TI  - The acid-base equilibrium in the cerebro-spinal fluid.

PMID- 16993478
TI  - The relation of the animal cell to electrolytes: II. The adsorption of hydrogen
      ions by living cells.

PMID- 16993479
TI  - The effect of varying the hydrogen ion concentration and of guanidin sulphate on
      the excitability of the neuro-myon of the frog.

PMID- 16993480
TI  - The four phases of heat-production of muscle.

PMID- 16993481
TI  - The metabolism of the salivary glands: I. The relation of the chorda tympani to
      the nitrogen metabolism of the submaxillary gland.

PMID- 16993482
TI  - The temperature coefficient of the velocity of a nervous impulse.

PMID- 16993483
TI  - Studies on muscular contraction: II. The relation between the maximal work and
      the tension developed in a muscle twitch, and the effects of temperature and
      extension.

PMID- 16993484
TI  - Variations in alveolar carbon dioxide pressure in relation to meals.

PMID- 16993485
TI  - Note on the supposed identity of the water-soluble vitamin B and secretin.

PMID- 16993486
TI  - On a probable error in determinations by means of the hydrogen electrode.

PMID- 16993487
TI  - The action of ions upon the frog's heart.

PMID- 16993488
TI  - The immediate action of volatile substances.

PMID- 16993490
TI  - On the fibrillation of the heart.

PMID- 16993489
TI  - Studies in the regeneration of denervated mammalian muscle: IV. Effects of
      massage and electrical treatment in secondary sutures.

PMID- 16993491
TI  - On recurring extra systoles and their relation to fibrillation.

PMID- 16993492
TI  - The substances needed for the growth of a pure culture of Colpidium colpoda.

PMID- 16993493
TI  - The oxygen use of muscle and the effect of sympathetic nerves on it.

PMID- 16993494
TI  - Effects on the frog's heart of varying the alkalinity and calcium content of the
      perfusing fluid.

PMID- 16993495
TI  - The regulation of the water content of the human organism.

PMID- 16993497
TI  - The replacement of potassium by uranium in perfusion of the heart.

PMID- 16993496
TI  - The regulation of the supply of energy in muscular contraction.

PMID- 16993498
TI  - Studies on muscular contraction: III. The influence of extension and temperature
      on the heat production in the muscle twitch.

PMID- 16993499
TI  - Studies on respiration and circulation in the cat: I. The influence of an acute
      anoxic anoxaemia on respiration and circulation.

PMID- 16993500
TI  - On the amount of heat liberated by bacillus coli when grown in the presence of
      free amino-acids.

PMID- 16993501
TI  - The physiological changes produced by radium rays and ultra-violet light in the
      egg of nereis.

PMID- 16993502
TI  - The coagulation of the blood: Part I. The role of calcium.

PMID- 16993503
TI  - The regulation of the reaction of the blood.

PMID- 16993504
TI  - The recovery process of excitable tissues: Part II.

PMID- 16993505
TI  - The physiology of the veins.

PMID- 16993506
TI  - The survival of motility in mammalian spermatozoa.

PMID- 16993507
TI  - Studies on respiration and circulation in the cat: II. The effects of haemorrhage
      and transfusion of gum-saline solution.

PMID- 16993509
TI  - The effect of cooling power of the atmosphere on body metabolism.

PMID- 16993508
TI  - The function of the urinary tubules in the frog.

PMID- 16993510
TI  - Experiments on the regulation of the blood's alkalinity: II.

PMID- 16993511
TI  - The action of diuretics.

PMID- 16993512
TI  - The coagulation of the blood: Part II. The clotting complex.

PMID- 16993513
TI  - The effects of respiration of oxygen on breathing and circulation.

PMID- 16993514
TI  - The comparative atrophy of the skeletal muscle after cutting the nerve and after
      cutting the tendon.

PMID- 16993515
TI  - The regulation of the excretion of water by the kidneys.

PMID- 16993516
TI  - On the relation of pulse pressure to the output of the heart.

PMID- 16993517
TI  - Exosmosis from animal cells.

PMID- 16993518
TI  - The electric response of denervated muscle.

PMID- 16993519
TI  - The identity of haemoglobin in human beings.

PMID- 16993520
TI  - The direct measurement of the partial pressure of oxygen in human blood.

PMID- 16993521
TI  - The effect of adrenalin upon respiration.

PMID- 16993522
TI  - The action of carbon dioxide on salt and water distribution in blood.

PMID- 16993523
TI  - The measurement of the oxygen content of the mixed venous blood, and of the
      volume of blood circulating per minute.

PMID- 16993524
TI  - Variations in alveolar carbon dioxide pressure in relation to meals: a further
      study.

PMID- 16993526
TI  - Studies on the physiology of capillaries: II. The reactions to local stimuli of
      the blood-vessels in the skin and web of the frog.

PMID- 16993525
TI  - The nature of the isometric twitch.

PMID- 16993527
TI  - On the path of conduction between auricle and ventricle in the amphibian and
      reptilian heart.

PMID- 16993528
TI  - The excretion of chlorides and bicarbonates by the human kidney.

PMID- 16993529
TI  - On the influence of changes of concentration of the H[unk] resp. OH' ions on the
      life of the tissue cells of vertebrates: I. The influence of temporary changes of
      reaction of the medium.

PMID- 16993530
TI  - Anoxaemia and the administration of oxygen.

PMID- 16993531
TI  - The heat-production and the mechanism of the veratrine contraction.

PMID- 16993532
TI  - The all-or-nothing response of sensory nerve fibres.

PMID- 16993533
TI  - The effect of section of the vagi on the respiration of the cat.

PMID- 16993534
TI  - On the coronary circulation in the heart-lung preparation.

PMID- 16993535
TI  - Observations on the melanophores of the frog.

PMID- 16993537
TI  - The sympathetic innervation of the skin of the toad.

PMID- 16993536
TI  - On secretion by the isolated kidney.

PMID- 16993538
TI  - The recovery heat-production in muscle.

PMID- 16993539
TI  - The nerve fibre constitution of peripheral nerves and of nerve roots.

PMID- 16993540
TI  - The origin of the electrical change in muscle.

PMID- 16993541
TI  - Reproduction in cell-communities.

PMID- 16993542
TI  - Nutrition on high-protein dietaries.

PMID- 16993543
TI  - Gaseous interchange in the stomach in the anaesthetised animal.

PMID- 16993544
TI  - The refractory phase in a reflex arc.

PMID- 16993546
TI  - The so-called compensatory hypertrophy of the testicle after unilateral
      castration.

PMID- 16993545
TI  - The renal function as judged by the excretion of vital dye-stuffs.

PMID- 16993547
TI  - On Golgi's internal apparatus in different physiological conditions of the
      mammary gland.

PMID- 16993548
TI  - The relations of carbon dioxide in acidified blood.

PMID- 16993549
TI  - Cheyne-stokes respiration: Part I. Production by adrenalin.

PMID- 16993551
TI  - Renal blood-flow and glomerular filtration.

PMID- 16993550
TI  - The secretion of sweat: Part I. Supposed inhibitory nerve fibres on the posterior
      nerve roots. Secretion after denervation.

PMID- 16993552
TI  - The maximum work and mechanical efficiency of human muscles, and their most
      economical speed.

PMID- 16993553
TI  - The action of dimethyltellurium dihaloids.

PMID- 16993554
TI  - The reaction of resting and active muscle.

PMID- 16993555
TI  - The relative excretion of urea and some other constituents of the urine.

PMID- 16993556
TI  - The regulation of the general circulation rate in man.

PMID- 16993557
TI  - Effects on the circulation of changes in the carbon-dioxide content of the blood.

PMID- 16993558
TI  - Acid production in shed blood.

PMID- 16993559
TI  - On the hydrogen-ion concentration and some related properties of normal human
      blood.

PMID- 16993561
TI  - The localisation of excretion in the uriniferous tubule.

PMID- 16993560
TI  - Studies on the physiology of capillaries: III. The innervation of the blood
      vessels in the hind legs of the frog.

PMID- 16993562
TI  - Glucose absorption in the renal tubules of the frog.

PMID- 16993564
TI  - Formation and distribution of phosphates in muscle.

PMID- 16993563
TI  - The secretion of sweat: Part II. The effect of vaso-constriction and of
      adrenaline.

PMID- 16993565
TI  - The relation of nerve-supply and blood flow to sweating produced by pilocarpine.

PMID- 16993566
TI  - The metabolism of the salivary glands: II. The blood sugar metabolism of the
      submaxillary gland.

PMID- 16993567
TI  - Salt and water elimination in man.

PMID- 16993568
TI  - Observations on augmented salivary secretion.

PMID- 16993569
TI  - The colloidal alkali reserve of the blood.

PMID- 16993570
TI  - The carbon dioxide partial pressure in body cavities and tissue spaces under
      various conditions.

PMID- 16993572
TI  - On the maximum work of human muscles especially the flexors of the elbow.

PMID- 16993571
TI  - Creatine formation in frog's muscle contracted by nicotine.

PMID- 16993573
TI  - Calcium chloride acidosis.

PMID- 16993574
TI  - The sympathetic innervation and the process of normal salivary secretion.

PMID- 16993575
TI  - Creatine formation during tonic muscle contraction.

PMID- 16993577
TI  - The effect of temperature on the isolated iris of the cat.

PMID- 16993576
TI  - The modification of the action of insulin by pituitary extract and other
      substances.

PMID- 16993578
TI  - An analysis of the effects of speed on the mechanical efficiency of human
      muscular movement.

PMID- 16993579
TI  - Observations on the respiratory centres.

PMID- 16993580
TI  - Pulmonary oedema and congestion in the heart-lung preparation.

PMID- 16993581
TI  - Humoral transmission of excitation on stimulating the vagus and sympathetic
      nerves of the frog's heart.

PMID- 16993582
TI  - Carbon dioxide tension and oxygen consumption during artificial respiration,
      acidosis and alkalosis.

PMID- 16993584
TI  - The action of vaso-constrictor substances on the arteries of the brain.

PMID- 16993583
TI  - The adrenalin and vagal types of apnoea.

PMID- 16993585
TI  - The activity of the Golgi apparatus in the neurones of Helix aspersa.

PMID- 16993586
TI  - The function of the tubules in kidney excretion.

PMID- 16993587
TI  - Antidromic action: Part I.

PMID- 16993588
TI  - On the effect of insulin on blood phosphate.

PMID- 16993589
TI  - The relative importance of the factors concerned in the formation of the urine.

PMID- 16993590
TI  - The influence of oxygen supply on the response of the isolated intestine to
      drugs.

PMID- 16993591
TI  - On the action of phlorhizin on the kidney.

PMID- 16993592
TI  - The metabolism of the salivary glands: III. The blood sugar metabolism of the
      submaxillary gland.

PMID- 16993593
TI  - On the nature of the sugar in blood.

PMID- 16993594
TI  - Studies on the respiration and circulation in the cat: II. The oxygen in the
      venous blood.

PMID- 16993596
TI  - Seasonal variation in the reticulated corpuscles of amphibian blood.

PMID- 16993595
TI  - Circulation after cessation of work, with some remarks on the calculation of
      circulation rate experiments according to the nitrous oxide method.

PMID- 16993597
TI  - A study of the chlorine interchange between corpuscles and plasma.

PMID- 16993598
TI  - Calibration of the reversion spectroscope for the estimation of CO in blood.

PMID- 16993599
TI  - Visual acuity and the resolving power of the eye.

PMID- 16993600
TI  - The relation between the external work produced and the time occupied in a single
      muscular contraction in man.

PMID- 16993601
TI  - The metabolism of the salivary glands: IV. The metabolism of the reducing
      substance of the submaxillary gland.

PMID- 16993602
TI  - The measurement of the tension of oxygen and carbon dioxide in the blood of the
      pulmonary artery in man.

PMID- 16993603
TI  - On the concentration of the blood and the effects of histamine in adrenal
      insufficiency.

PMID- 16993604
TI  - The influence of carbon dioxide on the interchange of ions between the corpuscles
      and the serum of blood.

PMID- 16993605
TI  - Pituitary secretion.

PMID- 16993606
TI  - Variations in the CO(2) content of the blood constituents in relation to meals.

PMID- 16993607
TI  - The effect of lactation on ovulation.

PMID- 16993609
TI  - Observations on the respiratory centres in the cat.

PMID- 16993608
TI  - On the nature of histamine action.

PMID- 16993610
TI  - Studies in muscle activity: I. The static effort.

PMID- 16993611
TI  - The photographic kymograph.

PMID- 16993612
TI  - On the situation and extent of the purely yellow zone in the spectrum.

PMID- 16993613
TI  - A simple apparatus for producing mechanical hemolysis and its practical use.

PMID- 16993614
TI  - The effect of concentration of the red blood corpuscles on the dissociation curve
      of blood.

PMID- 16993615
TI  - Studies on the respiration and circulation in the cat: III. The effect of rise of
      body temperature.

PMID- 16993616
TI  - An analysis of the production of heat in certain muscles of the hedgehog.

PMID- 16993617
TI  - The part played by the ducts in the pancreatic secretion.

PMID- 16993618
TI  - On the change in the nature of the blood sugar of diabetics caused by insulin.

PMID- 16993619
TI  - The influence of the nutritional condition of the animal on the hypoglycaemia
      produced by insulin.

PMID- 16993620
TI  - Studies on the physiology of plain muscle: I. The effect of alteration of
      hydrogen-ion concentration on the tone and contractions of plain muscle.

PMID- 16993621
TI  - A comparison between the colorimetric and the electrometric methods of
      determining the hydrogen ion concentration of blood.

PMID- 16993622
TI  - On a possible relation between the pancreas and the parathyroids.

PMID- 16993623
TI  - Isolation of different parts of the digestive tract as a method of studying its
      movements.

PMID- 16993624
TI  - On the absorption of insulin from the stomach.

PMID- 16993625
TI  - Studies on the physiology of plain muscle: II. The oxygen usage of plain muscle,
      and its relation to tonus.

PMID- 16993626
TI  - Does insulin influence the glycogenic function of the perfused liver of the
      turtle?

PMID- 16993627
TI  - The rate of recovery of nerves in asphyxia.

PMID- 16993628
TI  - Antidromic action: Part II. Stimulation of the peripheral nerves of the cat's
      hind foot.

PMID- 16993629
TI  - The vascular dilatation caused by the sympathetic and the course of vaso-motor
      nerves.

PMID- 16993630
TI  - On the ovarian factor concerned in the occurrence of oestrus.

PMID- 16993631
TI  - The regulation of respiration: Part I.

PMID- 16993632
TI  - An ergometer adaptable for either hand- or foot-movements.

PMID- 16993633
TI  - Nerve regeneration from one into the other of two rats united in siamese pairs.

PMID- 16993634
TI  - The relation between the work performed and the energy liberated in muscular
      contraction.

PMID- 16993635
TI  - The inseparability of the mechanical and thermal responses in muscle.

PMID- 16993636
TI  - Notes on temperature after spinal transection, with some observations on
      shivering.

PMID- 16993637
TI  - The relative influence of mental and muscular work on the pulse-rate and blood
      pressure.

PMID- 16993638
TI  - Hyperglycaemic and phlorhizin glycosuria in the heart-lung-kidney preparation.

PMID- 16993639
TI  - The heat production of muscles treated with caffein or subjected to prolonged
      discontinuous stimulation.

PMID- 16993640
TI  - The lactic acid in the blood of a resting man.

PMID- 16993641
TI  - Experimental hermaphroditism on quantitative lines: Intratesticular ovarian
      transplantation by the method of Sand.

PMID- 16993642
TI  - Cholin in the blood after parathyreoidectomy.

PMID- 16993643
TI  - The effect of hydrogen-ion concentration on the recovery process in muscle.

PMID- 16993644
TI  - The innervation of the pyloric sphincter of the rat.

PMID- 16993645
TI  - The regulation of respiration: Part II. Normal Type.

PMID- 16993647
TI  - Observations on the taking up of carbon monoxide by the haemoglobin in the
      spleen.

PMID- 16993646
TI  - The anaerobic processes involved in muscular activity.

PMID- 16993648
TI  - Note on the effect of external temperature on the circulation in man.

PMID- 16993649
TI  - Variations in the blood chlorides in relation to meals: Part I.

PMID- 16993650
TI  - The heat of combustion of glycogen in relation to muscular contraction.

PMID- 16993651
TI  - Localisation of the vaso-motor centre.

PMID- 16993652
TI  - A quantitative comparison between the energy liberated and the work performed by
      the isolated sartorius muscle of the frog.

PMID- 16993653
TI  - The reversion of haemolysis.

PMID- 16993654
TI  - The frequency of discharge from the spinal cord in the frog.

PMID- 16993655
TI  - The excretion of cholin in the urine.

PMID- 16993656
TI  - The influence of diuretics on the excretion of sugar.

PMID- 16993657
TI  - The suprarenal cortex of the male throughout the oestrous cycle.

PMID- 16993659
TI  - Chelonian respiration (tortoise).

PMID- 16993658
TI  - The concentration of lactic acid in the blood in experimental alkalaemia and
      acidaemia.

PMID- 16993660
TI  - The mutual influence of secretory stimuli in the submaxillary gland of the cat.

PMID- 16993661
TI  - Some peculiarities of the sympathetic innervation of the submaxillary gland of
      the cat.

PMID- 16993662
TI  - Secretion as a factor in elimination by the bird's kidney.

PMID- 16993663
TI  - Variations in the sensibility to pressure pain caused by nerve stimulation in
      man.

PMID- 16993664
TI  - Interrelation of parathyroids, suprarenals and pancreas.

PMID- 16993665
TI  - The metabolism of the salivary glands: V. The Process of Reconstruction of the
      Submaxillary Gland.

PMID- 16993666
TI  - The nerve fibre constitution of the nerves of the eye.

PMID- 16993667
TI  - The maximum realisable work of the flexors of the elbow.

PMID- 16993668
TI  - Variation of capillary diameter and antidromic action in the frog.

PMID- 16993669
TI  - On the blood phosphate after insulin convulsions.

PMID- 16993670
TI  - The effect of fatigue on the relation between work and speed, in contraction of
      human arm muscles.

PMID- 16993671
TI  - The localisation of excretion in the uriniferous tubule: Part II.

PMID- 16993672
TI  - The effect of insulin on the oxygen and carbon dioxide tensions in air between
      the skin and the muscles.

PMID- 16993673
TI  - Studies in muscle activity: II. The influence of speed on the mechanical
      efficiency.

PMID- 16993674
TI  - Mitral insufficiency.

PMID- 16993676
TI  - A method for the graphic registration of oxygen-consumption and carbon dioxide
      output; the respiratory exchange in decerebrate rigidity.

PMID- 16993675
TI  - Changes in the tensions of CO(2) and O(2) in gases injected under the skin and
      into the abdominal cavity.

PMID- 16993677
TI  - The regulation of the breathing after the ingestion of sugar.

PMID- 16993678
TI  - Factors affecting the theoretical maximum work of muscle.

PMID- 16993679
TI  - A vago-pressor reflex.

PMID- 16993681
TI  - The maximum frequency of reflex response in the spinal cat.

PMID- 16993680
TI  - Reversible haemolysis.

PMID- 16993682
TI  - The effect of carbon dioxide on the rate of recovery in nerve.

PMID- 16993683
TI  - A circulating scheme for recording respiratory metabolism.

PMID- 16993684
TI  - The dissociation of oxyhaemoglobin in the tissues.

PMID- 16993685
TI  - On the formation of sulphaemoglobin.

PMID- 16993686
TI  - The influence of chemical factors on the coronary circulation.

PMID- 16993688
TI  - Observations on pancreatic secretion.

PMID- 16993687
TI  - On measurement of the blood-coagulation time.

PMID- 16993689
TI  - The part played by the ala cinerea in vaso-motor reflexes.

PMID- 16993690
TI  - The action of oxalates and of citrates on circulating blood.

PMID- 16993691
TI  - The excitability of the anaemic medulla oblongata.

PMID- 16993692
TI  - The influence of the vagus on the islets of Langerhans: Part I. Vagus
      hypoglycaemia.

PMID- 16993693
TI  - Further observations on nutrition with diets rich in protein.

PMID- 16993694
TI  - Observations on the taking up of carbon monoxide by the haemoglobin of the
      spleen.

PMID- 16993695
TI  - Renal function in summer frogs and winter frogs.

PMID- 16993696
TI  - The changes in alveolar CO(2) pressure after violent exercise.

PMID- 16993697
TI  - The effect of curari and denervation upon the electrical excitability of striated
      muscle.

PMID- 16993698
TI  - The influence of the blood supply on pancreatic secretion.

PMID- 16993699
TI  - On the location and nature of the action of insulin.

PMID- 16993700
TI  - The effect of insulin on blood volume.

PMID- 16993701
TI  - The glomerular control of the kidney blood flow.

PMID- 16993702
TI  - On the constancy of the basal metabolism.

PMID- 16993703
TI  - The effect of variations in blood-pressure on pulse wave velocity in the brachial
      artery in man.

PMID- 16993704
TI  - A comparison of blood curves constructed with arterial and with venous blood.

PMID- 16993705
TI  - Vaso-motor centres: Part III. Spinal vascular (and other autonomic) reflexes and
      the effect of strychnine on them.

PMID- 16993706
TI  - The effect of cerebral anaemia upon blood-pressure and respiration.

PMID- 16993707
TI  - Twenty-four hour observations on the metabolism of normal and starving subjects.

PMID- 16993708
TI  - Influence of CO(2) on the absorption of alcohol by the gastric mucosa.

PMID- 16993709
TI  - The influence of the ovary on pituitary secretion; a probable factor in
      parturition.

PMID- 16993710
TI  - The influence of insulin on the blood sugar in the heart-lung preparation.

PMID- 16993711
TI  - The formation of the v wave in the venous pulse.

PMID- 16993712
TI  - Heat regulation and water exchange: V. The Phase of Blood Dilution in Man.

PMID- 16993713
TI  - Heat regulation and water exchange: VI. The Mobilisation of Water and Salt in
      Warm Environments.

PMID- 16993714
TI  - The mechanism of the splenic reaction to general CO poisoning.

PMID- 16993715
TI  - Latent glandular hermaphroditism. new "unbolting" experiments.

PMID- 16993717
TI  - The adjustment of the buoyancy of the larva of Corethra plumicornis.

PMID- 16993716
TI  - On some conditions affecting the perfusion of isolated mammalian organs.

PMID- 16993718
TI  - On the migration of ova in the rabbit.

PMID- 16993719
TI  - The effect of certain changes in the perfusate upon the isolated auricles of the
      rabbit.

PMID- 16993720
TI  - Studies on the respiration and circulation of the cat: IV. The heart output
      during respiratory obstruction.

PMID- 16993721
TI  - The significance of the action of pituitrin on the splenic volume.

PMID- 16993722
TI  - The action of adrenalin on the central nervous system.

PMID- 16993723
TI  - The effect on muscle contraction of sympathetic stimulation and of various
      modifications of conditions.

PMID- 16993724
TI  - The effect of changes in venous blood-pressure on the rate of flow through, and
      the gaseous metabolism of the kidney.

PMID- 16993725
TI  - The relation of the thyroid gland to the action of insulin.

PMID- 16993726
TI  - On the conditions of respiration with the chest open.

PMID- 16993728
TI  - Further observations on the production of anhydraemia with insulin.

PMID- 16993727
TI  - On the effect of adrenaline on the respiratory centre.

PMID- 16993729
TI  - On haem in nature.

PMID- 16993730
TI  - Observations on the pulmonary circulation: Pulmonary Circulation in the Heart
      Lung Preparation.

PMID- 16993731
TI  - The relation of ovarian function to menstruation.

PMID- 16993733
TI  - The double innervation of the m. gastrocnemius.

PMID- 16993732
TI  - The relation between the size of the heart and the oxygen content of the arterial
      blood.

PMID- 16993734
TI  - On helicorubin and its relation to haemoglobin.

PMID- 16993735
TI  - The effect of pituitary extract on the secretion and composition of the urine.

PMID- 16993736
TI  - Length of muscle, and the heat and tension developed in an isometric contraction.

PMID- 16993737
TI  - Observations on the combination of CO(2) in the blood of the bull frog (Rana
      catesbiana).

PMID- 16993738
TI  - An analysis of the heat production during a contraction in which work is
      performed.

PMID- 16993739
TI  - The coagulation of blood plasma when divested of corpuscles.

PMID- 16993740
TI  - Note on the composition of alveolar air at extreme heights.

PMID- 16993741
TI  - A study of the mechanism of insulin: Part I. The action of insulin and of the
      salts of guanidine on the permeability of the mammalian erythrocyte.

PMID- 16993742
TI  - The reduced sensitivity to insulin of rats and mice fed on a carbohydrate-free,
      excess-fat diet.

PMID- 16993743
TI  - The spread of activity in the tenuissimus muscle of the cat and in other complex
      muscles.

PMID- 16993744
TI  - The effect of the circulation on the electrical resistance of the skin.

PMID- 16993745
TI  - A method for the perfusion of the kidney with deoxygenated blood of known oxygen
      tension.

PMID- 16993746
TI  - Studies on the innervation of smooth muscle: II. On the Frequency of Nerve
      Impulses Entering and Leaving the Superior Cervical Ganglion.

PMID- 16993747
TI  - On cellular changes in intestinal fat absorption.

PMID- 16993748
TI  - The effects of different salts on the heat-production of muscle.

PMID- 16993749
TI  - On the combination of nitric oxide with haemoglobin.

PMID- 16993750
TI  - A closed circuit heart lung preparation: I. Effect of alterations in blood
      volume.

PMID- 16993751
TI  - The influence of O(2)-tension in the inspired air upon the O(2)-tension in the
      tissues.

PMID- 16993752
TI  - The relation in diuresis between volume of urine and concentration of a diuretic
      with the influence of temperature upon it.

PMID- 16993753
TI  - The direct action of insulin on fat metabolism.

PMID- 16993754
TI  - On haemochromogen and the relation of protein to the properties of the
      haemoglobin molecule.

PMID- 16993755
TI  - The effect of pituitrin on the fatty acid of the liver.

PMID- 16993756
TI  - The influence of the spleen in carbon monoxide poisoning.

PMID- 16993757
TI  - The mechanism of pancreatic digestion-the function of secretin.

PMID- 16993758
TI  - Insulin and the pituitrin "fat liver".

PMID- 16993759
TI  - The maximum work of the several muscles of the forearm.

PMID- 16993761
TI  - The secretion of sweat and vaso-dilatation produced by pilocarpine.

PMID- 16993760
TI  - Tissue oxygen-tension with special reference to tetany and convulsions.

PMID- 16993762
TI  - The role of the phosphates in carbohydrate metabolism in skeletal muscle.

PMID- 16993764
TI  - The course of the blood of the renal artery.

PMID- 16993763
TI  - Effect of thyroid feeding on sugar tolerance.

PMID- 16993765
TI  - The circulation in skeletal muscle, chiefly in relation to the effect of the
      depressor nerve of the rabbit.

PMID- 16993766
TI  - The influence of temperature on the equilibrium between oxygen and haemoglobin of
      various forms of life.

PMID- 16993767
TI  - A contribution to the physiology of the spleen.

PMID- 16993768
TI  - Studies on the innervation of smooth muscle: III. Splanchnic Effects on the Lower
      End of the Oesophagus and Stomach of the Cat.

PMID- 16993769
TI  - The in vivo permeability of the red corpuscles of the rabbit.

PMID- 16993770
TI  - The relation of secretin formation to the entrance of acid chyme into the small
      intestine-the properties of secretin.

PMID- 16993772
TI  - The action of adrenalin and ergotamine on the uterus of the rabbit.

PMID- 16993771
TI  - On the nature and significance of vagus escape.

PMID- 16993773
TI  - Titles of works by J. N. Langley.

PMID- 16993774
TI  - The effect of stimulation of the vagi on the pyloric region of the stomach.

PMID- 16993775
TI  - The influence of exercise on the inorganic phosphates of the blood and urine.

PMID- 16993776
TI  - The impulses produced by sensory nerve endings: Part I.

PMID- 16993777
TI  - On the elasticity of skeletal muscles.

PMID- 16993778
TI  - The interpretation of the electromyogram of striated muscle during contractions
      set up by central nervous excitation.

PMID- 16993779
TI  - On the factors concerned in the production of pulmonary oedema.

PMID- 16993780
TI  - The impulses produced by sensory nerve-endings: Part II. The response of a Single
      End-Organ.

PMID- 16993781
TI  - The action of ions upon intra-auricular conduction in the tortoise.

PMID- 16993782
TI  - The vaso-dilator action of histamine, and its physiological significance.

PMID- 16993783
TI  - The central and reflex regulation of the heart rate.

PMID- 16993785
TI  - A method for the study of the perfused pancreas.

PMID- 16993784
TI  - A method of measuring directly the total and partial pressures of the gases in
      blood.

PMID- 16993786
TI  - The normal co(2)- and o(2)-tensions in the tissues of various animals.

PMID- 16993787
TI  - An analysis of the initial heat production in the voluntary muscle of the
      tortoise.

PMID- 16993788
TI  - Reaction to drugs of strips of the rabbit's gastric musculature.

PMID- 16993789
TI  - Cardiovascular reflexes.

PMID- 16993791
TI  - Histamine shock.

PMID- 16993790
TI  - Studies on the physiology of plain muscle: The effect of alteration of initial
      length on the tension produced on contraction.

PMID- 16993792
TI  - The action of alcohol upon conduction in the auricle of the tortoise.

PMID- 16993793
TI  - On the influence of hydrogen ion concentration and of anoxaemia upon the heart
      volume.

PMID- 16993794
TI  - The conduction of a nervous impulse in a narcotised region of nerve.

PMID- 16993795
TI  - The osmotic pressure of the proteins of human serum and plasma.

PMID- 16993796
TI  - The blood count and body temperature in normal rats.

PMID- 16993798
TI  - The conduction of respiratory nervous impulses through regions of block produced
      by pressure.

PMID- 16993797
TI  - Studies on the relation of work and heat in tortoise muscle.

PMID- 16993799
TI  - The influence of length on the responses of unstriated muscle to electrical and
      chemical stimulation, and stretching.

PMID- 16993800
TI  - The action of pituitary extract upon the pregnant uterus of the rabbit.

PMID- 16993801
TI  - On cellular activity and cellular structure as studied in the thyroid gland.

PMID- 16993802
TI  - The venous pressure of the eye and its relation to the intra-ocular pressure.

PMID- 16993803
TI  - The secretion of pancreatic juice.

PMID- 16993804
TI  - The spleen and the resistance of red cells.

PMID- 16993805
TI  - The determination of the hydrogen-ion concentration of the blood.

PMID- 16993806
TI  - On the output of haemoglobin and blood by the spleen.

PMID- 16993807
TI  - The impulses produced by sensory nerve endings: Part 3. Impulses set up by Touch
      and Pressure.

PMID- 16993808
TI  - The influence of calcium on the isometric response of the frog's heart.

PMID- 16993809
TI  - Secretin and the portal circulation.

PMID- 16993810
TI  - A note on the elasticity of skeletal muscles.

PMID- 16993811
TI  - The production of sugar in the perfused liver from non-protein sources.

PMID- 16993812
TI  - The peripheral innervation of the vessels of the external ear of the rabbit.

PMID- 16993813
TI  - The reaction between acetyl choline and muscle cells.

PMID- 16993814
TI  - The antagonism of acetyl choline by atropine.

PMID- 16993815
TI  - Effect of parathyroid feeding on the thyroid.

PMID- 16993816
TI  - Studies on the internal secretions of the ovary: I. The distribution in the ovary
      of the oestrus-producing hormone.

PMID- 16993817
TI  - The influence of the vagus on the islets of langerhans: Part II. The effect of
      cutting the vagus upon sugar tolerance.

PMID- 16993818
TI  - Observations on the effect of anoxAEmia upon heart and circulation.

PMID- 16993820
TI  - The relation between the corpus luteum and the mammary gland.

PMID- 16993819
TI  - The equation expressing the excretion of a diuretic and its relation to diffusion
      processes.

PMID- 16993821
TI  - The coronary circulation in the isolated heart.

PMID- 16993822
TI  - The arterial pressure in the eye.

PMID- 16993823
TI  - The application of the ethyl iodide method to the determination of the
      circulation rate in women.

PMID- 16993824
TI  - The chronaxie in tetany: The effect on the chronaxie of thyreoparathyreoidectomy,
      the administration of guanidin and of di-methyl guanidin.

PMID- 16993825
TI  - The effect of CO(2) on the absorption of alcohol and the influence of alcohol on
      the diffusion of CO(3) in the small intestine.

PMID- 16993826
TI  - Insulin and the production of acetone bodies by the perfused liver.

PMID- 16993827
TI  - The impulses produced by sensory nerve-endings: Part 4. Impulses from Pain
      Receptors.

PMID- 16993829
TI  - The buffering power of the blood of Maia squinado.

PMID- 16993828
TI  - Reversal of the action of adrenaline.

PMID- 16993830
TI  - On the cellular mechanism of bile secretion and its relation to the Golgi
      apparatus of the liver cell.

PMID- 16993831
TI  - The sensitising action of alkalies.

PMID- 16993832
TI  - The differential paralysis of cardiac nerve endings and muscle.

PMID- 16993833
TI  - The recovery heat production in tortoise's muscle.

PMID- 16993834
TI  - The "interference" of two flexion-reflexes; an examination of Veszi's experiment.

PMID- 16993835
TI  - Effect upon platelets and on blood coagulation of injecting foreign particles
      into the blood stream.

PMID- 16993837
TI  - Myothermic observations on the dogfish.

PMID- 16993836
TI  - Studies on the internal secretions of the ovary: II. The effects of injection of
      the oestrus producing hormone during pregnancy.

PMID- 16993838
TI  - The antagonism of acetyl choline by methylene blue.

PMID- 16993839
TI  - The chemical regulation of capillary tone.

PMID- 16993840
TI  - The role of the phosphates in carbohydrate metabolism in skeletal muscle: Part
      II. A comparison between the muscles of normal, fatigued and depancreatised
      animals.

PMID- 16993841
TI  - On the regeneration of blood after haemorrhage.

PMID- 16993842
TI  - On the innervation and secretory path of the thyroid gland.

PMID- 16993843
TI  - The anaerobic delayed heat production in muscle.

PMID- 16993844
TI  - Prolonged alterations of oxygen pressure in the inspired air with special
      reference to tissue oxygen tension, tissue carbon dioxide tension and
      haemoglobin.

PMID- 16993845
TI  - The rate of distribution of dissolved gases between the red blood corpuscle and
      its fluid environment: Part I. Preliminary experiments on the rate of uptake of
      oxygen and carbon monoxide by sheep's corpuscles.

PMID- 16993846
TI  - The regulation of the energy output of the heart.

PMID- 16993847
TI  - Automatic sampling of alveolar air, particularly for measurement of the
      circulation with ethyl iodide vapour.

PMID- 16993848
TI  - Observations on the contractility of lacteals: Part I.

PMID- 16993849
TI  - Reflex effects of active muscular contraction.

PMID- 16993850
TI  - Vascular reactions of the skin to injury: Part VIII. The resistance of the human
      skin to constant currents, in relation to injury and vascular response.

PMID- 16993851
TI  - The action of the vagus on the spleen.

PMID- 16993852
TI  - Studies on the internal secretions of the ovary: III. The effects of injection of
      oestrin during lactation.

PMID- 16993853
TI  - The osmotic pressure of the aqueous humour and its physiological significance.

PMID- 16993854
TI  - The localisation of receptors involved in the reflex regulation of the heart
      rate.

PMID- 16993855
TI  - The influence of insulin upon the mammalian heart.

PMID- 16993856
TI  - The two phases of heat production of nerve.

PMID- 16993857
TI  - The static effort and the excretion of uric acid.

PMID- 16993858
TI  - Foetal blood-gas tensions and gas transfusion through the placenta of the goat.

PMID- 16993859
TI  - Studies on the internal secretions of the ovary: IV. The significance of the
      occurrence of oestrin in the placenta.

PMID- 16993860
TI  - The nature of the vaso-dilator constituents of certain tissue extracts.

PMID- 16993861
TI  - Observations on the contractility of lacteals: Part II.

PMID- 16993862
TI  - The synergism between alcohols and other drugs.

PMID- 16993863
TI  - The influence of temperature on the mechanical responses of certain unstriated
      muscles.

PMID- 16993864
TI  - The hydrogen ion concentration of the muscles of the cat.

PMID- 16993865
TI  - On the action of pilocarpine.

PMID- 16993867
TI  - The spinal reflexes of the skate.

PMID- 16993866
TI  - Reaction of smooth muscle to the h-ion concentration.

PMID- 16993868
TI  - Observations on the motor twitch and on reflex inhibition of the tendon-jerk of
      m. supraspinatus.

PMID- 16993869
TI  - Negative pressure pulmonary ventilation in the heart lung preparation.

PMID- 16993870
TI  - A method of propelling air round small enclosed circuits.

PMID- 16993871
TI  - The lactic acid maximum of cardiac muscle.

PMID- 16993872
TI  - Fatigue, retention of action current and recovery in crustacean nerve.

PMID- 16993873
TI  - The effect of frequency of stimulation on the heat production of nerve.

PMID- 16993875
TI  - Adrenin and the splanchnic nerve.

PMID- 16993874
TI  - The stretch reflex as a spinal process.

PMID- 16993876
TI  - The physiological significance of "phosphagen".

PMID- 16993877
TI  - A source of error in measurement of the circulation rate by henderson and
      haggard's method.

PMID- 16993878
TI  - The adjuvant action of the lactate ion on the vaso-dilator effect of sodium
      nitrite.

PMID- 16993879
TI  - Protracted oestrus induced by ovarian extracts.

PMID- 16993880
TI  - The initial phase of reflex inhibitory relaxation in extensor muscles.

PMID- 16993881
TI  - Upon inhibitory relaxations evoked by reflex stimuli of constant intensity acting
      against varied magnitudes of extensor tone.

PMID- 16993882
TI  - Studies on the movements of the alimentary canal: I. The effects of electrolytes
      on the rhythmical contractions of the isolated mammalian intestine.

PMID- 16993883
TI  - The depressor (vasodilator) action of adrenaline.

PMID- 16993884
TI  - The action of histamine on the blood vessels of the rabbit.

PMID- 16993885
TI  - Experiments on visceral sensation: Part I. The relation of pain to activity in
      the oesophagus.

PMID- 16993886
TI  - The action of insulin on the aseptically perfused heart.

PMID- 16993887
TI  - The permeability and diameter of the capillaries in the web of the brown frog (R.
      temporaria) when perfused with solutions containing pituitary extract and horse
      serum.

PMID- 16993888
TI  - The variation in the unit of the oestrus-producing hormone.

PMID- 16993889
TI  - Studies on nerve metabolism: I. The influence of oxygen lack on heat production
      and action current.

PMID- 16993890
TI  - The relationship between the volume of the heart and its oxygen usage.

PMID- 16993891
TI  - The circulation of body fluids in the frog.

PMID- 16993892
TI  - The influence of various sugars on the respiratory quotient: A contribution to
      the significance of the R.Q.

PMID- 16993893
TI  - Further observations on oxygen acclimatisation.

PMID- 16993894
TI  - The hydrogen-ion concentration of blood corpuscles.

PMID- 16993895
TI  - The effect upon the threshold for nervous excitation of the length of nerve
      exposed, and the angle between current and nerve.

PMID- 16993896
TI  - The action of light on the eye: Part I. The discharge of impulses in the optic
      nerve and its relation to the electric changes in the retina.

PMID- 16993897
TI  - Observations upon the size of the spleen.

PMID- 16993898
TI  - The blood in the spleen pulp.

PMID- 16993899
TI  - The action of visible light on the haematoporphyrin sensitised organs.

PMID- 16993900
TI  - Observations on the ethyl iodide method for the determination of heart output.

PMID- 16993901
TI  - The action of hirudin upon thrombin.

PMID- 16993902
TI  - The influence of posture on the volume of the reserve air.

PMID- 16993903
TI  - Reactions of isolated systemic and coronary arteries.

PMID- 16993904
TI  - The pressure equilibrium of the eye.

PMID- 16993905
TI  - Observations upon a pilomotor reaction in response to faradism.

PMID- 16993906
TI  - Studies on the circulation rate in man: I. Critical examination of ethyl iodide
      method.

PMID- 16993907
TI  - The reaction between acetyl choline and muscle cells: Part II.

PMID- 16993908
TI  - Further observations on the reaction of smooth muscle to the H-ion concentration.

PMID- 16993909
TI  - Vascular properties of traumatised and laked bloods.

PMID- 16993910
TI  - The nervous motive energy: Reply to Sybil Cooper and E. D. Adrian.

PMID- 16993911
TI  - Comparative effect of various drugs upon the coronary circulation.

PMID- 16993912
TI  - Is there "transitional decrement" in narcotised nerve?

PMID- 16993913
TI  - More reflex effects of active muscular contraction.

PMID- 16993914
TI  - The interrelation of number, volume, diameter and area of mammalian erythrocytes.

PMID- 16993915
TI  - The influence of the vagus on the islets of Langerhans: Part III. Further
      experiments on vagotomy.

PMID- 16993917
TI  - Quantitative observations on thyroxine and allied substances: I. The use of
      tadpoles.

PMID- 16993916
TI  - Studies on the internal secretions of the ovary: V. The oestrus-inhibiting
      function of the corpus luteum.

PMID- 16993918
TI  - The immediate products of post-mortem glycogenolysis in mammalian muscle and
      liver.

PMID- 16993919
TI  - Changes in oxygen consumption during metamorphosis induced by thyroid
      administration in the axolotl.

PMID- 16993921
TI  - A discussion on the part played by the supravestibular connections in decerebrate
      rigidity.

PMID- 16993920
TI  - The action of light on the eye: Part II. The processes involved in retinal
      excitation.

PMID- 16993922
TI  - The blood-pressure reflexes of the rabbit under urethane anaesthesia.

PMID- 16993923
TI  - The origin of the glucose in the hyperglycaemia induced by pituitrin.

PMID- 16993924
TI  - Bile salts and secretin as cholagogues.

PMID- 16993926
TI  - The effect of atropine, ergotamine, and pituitrin on phlorhizin glycosuria.

PMID- 16993925
TI  - The significance of the diastolic and systolic blood-pressures for the
      maintenance of the coronary circulation.

PMID- 16993927
TI  - A double perfusion-pump.

PMID- 16993928
TI  - The effect of the "heart-tonics" and other drugs upon the heart-tone and coronary
      circulation.

PMID- 16993929
TI  - The causation of the anoestrous period.

PMID- 16993930
TI  - The effect of temperature on the acidity of the skin.

PMID- 16993931
TI  - Photographic methods of estimating the percentage saturation of haemoglobin with
      various gases: I. The ratio of oxyhaemoglobin to carboxyhaemoglobin.

PMID- 16993932
TI  - Oxidation processes occurring in the system plasma (serum)-potassium
      ferricyanide.

PMID- 16993933
TI  - The oxygen usage of the kidney.

PMID- 16993934
TI  - Further observations on phosphagen.

PMID- 16993935
TI  - The influence of acid base equilibrium on the activities of blood vessels.

PMID- 16993936
TI  - The action of insulin and sugar on the respiratory quotient and metabolism of the
      heart-lung preparation.

PMID- 16993938
TI  - The factors influencing the concentration of hydrochloric acid during gastric
      digestion.

PMID- 16993939
TI  - Variations in the acidity and total chloride contained in the secretion from an
      isolated pavlov pouch in the dog.

PMID- 16993937
TI  - The action of insulin on the perfused mammalian liver.

PMID- 16993940
TI  - The relation of synthalin to carbohydrate metabolism.

PMID- 16993941
TI  - The enzymic processes in mammalian skeletal muscle.

PMID- 16993942
TI  - The influence of mechanical factors of the circulation upon the heart volume.

PMID- 16993943
TI  - Experiments on visceral sensation: Part II. The sensation of "nausea" and
      "sinking"; oesophageal reflexes and counter-irritation.

PMID- 16993944
TI  - Excitation of bent nerve.

PMID- 16993945
TI  - The effect of insulin on acetonuria.

PMID- 16993946
TI  - Concerning the "central" control of the peripheral circulation.

PMID- 16993947
TI  - The internal conductivity of non-irritable muscle.

PMID- 16993948
TI  - A new electrical recording system for physiological work.

PMID- 16993949
TI  - The influence of the protein intake on the basal metabolism.

PMID- 16993950
TI  - Tissue oxygen tension and haemoglobin.

PMID- 16993951
TI  - The action of light on the eye: Part III. The interaction of retinal neurones.

PMID- 16993953
TI  - Extensor reflexes in the fore-limb.

PMID- 16993952
TI  - Studies in the pulmonary circulation: I. The vaso-motor supply.

PMID- 16993954
TI  - Further observations on the vaso-motor reflexes and associated phenomena.

PMID- 16993955
TI  - The role of the corpus luteum in the maintenance of pregnancy.

PMID- 16993956
TI  - Effects of variations in intensity and frequency on the contractions of the
      stomach obtained by stimulation of the vagus nerve.

PMID- 16993957
TI  - The coronary circulation: I. The effect of changes of the blood-pressure and of
      the output of the heart.

PMID- 16993958
TI  - The distribution of phosphorus compounds in the blood of certain mammals.

PMID- 16993959
TI  - The influence of alcohol on absorption of glucose: Part I.

PMID- 16993960
TI  - The identical source of work and heat in muscular contraction.

PMID- 16993961
TI  - On the fluctuation in the composition of the alveolar air during the respiratory
      cycle in muscular exercise.

PMID- 16993962
TI  - The arterial blood in ammonium chloride acidosis.

PMID- 16993963
TI  - The conditions governing the blood capacity of the lungs.

PMID- 16993964
TI  - Some properties of the separated active principles of the pituitary (posterior
      lobe).

PMID- 16993965
TI  - Vasomotor effects of stimulating the right splanchnic nerve.

PMID- 16993966
TI  - The pharmacodynamical action of chloralose.

PMID- 16993967
TI  - The effect of ergotoxin on phlorrhizin glycosuria.

PMID- 16993968
TI  - The isolation of secretin-its chemical and physiological properties.

PMID- 16993969
TI  - The effect of alcohol on the absorption of glucose from the alimentary tract:
      Part II.

PMID- 16993970
TI  - The incidence of central inhibition on restricted fields of motor-units.

PMID- 16993971
TI  - The concentration and diffusion of inorganic phosphate in living muscle.

PMID- 16993972
TI  - The effect of pregnancy and menstruation on the size of the spleen.

PMID- 16993973
TI  - The measurement of the diameter of erythrocytes by the diffraction method.

PMID- 16993974
TI  - A study of the electrical field surrounding skeletal muscle.

PMID- 16993975
TI  - The effect of experimental anaemia on the size of the spleen.

PMID- 16993976
TI  - The discharge of impulses in motor nerve fibres: Part I. Impulses in single
      fibres of the phrenic nerve.

PMID- 16993977
TI  - Studies in muscular activity: I. Determination of the rate of circulation of
      blood in man at work.

PMID- 16993978
TI  - Studies in muscular activity: II. A nomographic description of expired air.

PMID- 16993979
TI  - Studies in muscular activity: III. Dynamical changes occurring in man at work.

PMID- 16993981
TI  - Subliminal fringe in spinal flexion.

PMID- 16993980
TI  - Studies in muscular activity: IV. The "steady state" and the respiratory quotient
      during work.

PMID- 16993982
TI  - Note on the electric response of nerve to two stimuli.

PMID- 16993983
TI  - The oxygen consumption of the frog's heart: I.

PMID- 16993984
TI  - Oxygen consumption of the frog's heart: II. Effect of Lipoids, Ions and
      Narcotics.

PMID- 16993985
TI  - Nerve excitation by multipolar electrodes.

PMID- 16993986
TI  - Some factors involved in the concentration of blood by the spleen.

PMID- 16993988
TI  - The cholesterol content of normal tissues and the effect of intravenous
      injections of cholesterol thereon.

PMID- 16993987
TI  - The effect of oxygen lack on surviving smooth muscle.

PMID- 16993989
TI  - The measurement of the oxygen capacity of haemoglobin.

PMID- 16993990
TI  - The action of glucosone upon different species of animals.

PMID- 16993991
TI  - A comparison of the effects of adrenaline and pituitrin on the portal
      circulation.

PMID- 16993992
TI  - On the latency of negative after-images following stimulation of different areas
      of the retina.

PMID- 16993993
TI  - An apparatus for the continuous recording of the oxygen consumption of small
      animals.

PMID- 16993994
TI  - The effect of hyper-respiration on the blood-pressure in man.

PMID- 16993995
TI  - Nerve fibres in the pituitary of a rabbit.

PMID- 16993996
TI  - Circulatory and respiratory changes in response to muscular exercise in man.

PMID- 16993997
TI  - Action of calcium ions on the frog's heart.

PMID- 16993998
TI  - The automatic regulation of gastric acidity.

PMID- 16993999
TI  - A vasodilator action of acetates.

PMID- 16994000
TI  - On the supposed relation between surface area and haemoglobin content in the red
      cells of mammalia.

PMID- 16994002
TI  - A note on the action of insulin in normal persons.

PMID- 16994001
TI  - Studies of reflex activity in the involuntary nervous system: I. Depressor
      Reflexes.

PMID- 16994003
TI  - The respiratory quotient after evisceration in cats.

PMID- 16994004
TI  - A non-specific pressor principle derived from a variety of tissues.

PMID- 16994005
TI  - Plurisegmental innervation in the frog.

PMID- 16994007
TI  - The role of the thyroid and parathyroid glands in vaso-motor reflexes.

PMID- 16994006
TI  - A method of oxygenating blood.

PMID- 16994008
TI  - The relation of active to inactive fibres in fractional contraction of muscle.

PMID- 16994009
TI  - A note on the effect of sodium sulphate on the oxygen usage of the kidney.

PMID- 16994010
TI  - The action of strychnine on sensory end organs in muscle and skin of the frog.

PMID- 16994011
TI  - The influence of vitamen A deficiency on the oestrous cycle of the rat.

PMID- 16994012
TI  - The effect of the responses of the soleus muscle of an alcohol block on the
      sciatic nerve.

PMID- 16994013
TI  - The determination of the carbon dioxide content of the mixed venous blood: Part
      I. The effect of oxygenation and the critical oxygen tension.

PMID- 16994014
TI  - The effect of muscular exercise on the oxygen capacity of the blood of man.

PMID- 16994015
TI  - The hydrogen ion concentration of the isolated uterus.

PMID- 16994016
TI  - Studies in the pulmonary circulation: II. The action of adrenaline and nicotine.

PMID- 16994017
TI  - The distribution of the blood in the coronary blood vessels.

PMID- 16994018
TI  - Crossed extensor reflexes and their interaction.

PMID- 16994020
TI  - Note on the central nervous system of the crayfish.

PMID- 16994019
TI  - The reversible loss of excitability in isolated amphibian voluntary muscle.

PMID- 16994021
TI  - Specific nerve impulses.

PMID- 16994022
TI  - The nervous regulation of respiration: Response of the human subject to
      interruption of the air supply.

PMID- 16994023
TI  - On the renal threshold for chloride in man.

PMID- 16994024
TI  - A study of some factors influencing intestinal movements.

PMID- 16994025
TI  - The discharge of impulses in motor nerve fibres: Part II. The frequency of
      discharge in reflex and voluntary contractions.

PMID- 16994026
TI  - Standardization of thyroid preparations.

PMID- 16994027
TI  - The efficiency of bicycle-pedalling, as affected by speed and load.

PMID- 16994029
TI  - The action of extract of pituitary on the blood sugar after pancreatectomy.

PMID- 16994028
TI  - The disappearance of histamine from autolysing lung tissue.

PMID- 16994030
TI  - Fatigue of the sense organs in muscle.

PMID- 16994031
TI  - Adsorption of haemoglobin by muscle tissue.

PMID- 16994032
TI  - The effect of temperature on the equilibrium of carbon dioxide and blood and the
      heat of ionization of haemoglobin.

PMID- 16994033
TI  - The coronary circulation: II. The effect of changes of temperature and of heart
      rate.

PMID- 16994034
TI  - The determination of the carbon dioxide content of the mixed venous blood: Part
      II. Carbon dioxide equilibria between mixed venous blood and rebreathed airs.

PMID- 16994035
TI  - The depolarization of crustacean nerve by stimulation or oxygen want.

PMID- 16994036
TI  - Methods for testing for the presence of adrenal cortex hormone.

PMID- 16994038
TI  - The lethal effects of ultrasonic radiation.

PMID- 16994037
TI  - Adrenaline vasodilatation.

PMID- 16994039
TI  - Maternal control of the placental glycogen.

PMID- 16994040
TI  - The identity of the response of muscle to direct and indirect stimulation.

PMID- 16994042
TI  - Studies on ovulation: I. The relation of the anterior pituitary body to ovulation
      in the rabbit.

PMID- 16994041
TI  - The significance of the occurrence of oestrin in male urine.

PMID- 16994043
TI  - The assay of oestrin.

PMID- 16994044
TI  - A mechanical stromuhr.

PMID- 16994045
TI  - The relationship of peptic activity to neutral chloride secretion during gastric
      digestion in man.

PMID- 16994046
TI  - A convenient form of closed-circuit respiratory apparatus for measuring
      simultaneously the carbon dioxide output and the oxygen intake over short or long
      periods.

PMID- 16994047
TI  - The electric response of nerve to two stimuli.

PMID- 16994048
TI  - On the form of the action potential wave in nerve.

PMID- 16994049
TI  - Studies on water diuresis: Part I. The effect of decerebration, anaesthesia and
      morphia upon water diuresis.

PMID- 16994050
TI  - A photographic method for the estimation of coloured solutions with special
      reference to visual purple.

PMID- 16994052
TI  - Influence on intestinal movements of electrolytes in the lumen of isolated
      segments.

PMID- 16994051
TI  - The combination of carbon dioxide with muscle: its heat of neutralization and its
      dissociation curve.

PMID- 16994053
TI  - The response of smooth muscle to stimulation of the vagus nerve.

PMID- 16994054
TI  - A method of recording reflex muscular contractions in man.

PMID- 16994055
TI  - The impulse discharge from the pacinian corpuscle.

PMID- 16994057
TI  - The action of posterior pituitary pressor extract on the rabbit's vascular
      system.

PMID- 16994056
TI  - The physico-chemical properties of the vitreous body.

PMID- 16994058
TI  - The vascular reactions of the colonic mucosa of the dog to fright.

PMID- 16994059
TI  - The effects of exercise on the vascular conditions in the spleen and the colon.

PMID- 16994060
TI  - An improved type of pump for artificial respiration.

PMID- 16994061
TI  - A method of estimating phosphagen and some other phosphorus compounds in muscle
      tissue.

PMID- 16994062
TI  - Tissue oxygen tension and carbon monoxide poisoning.

PMID- 16994063
TI  - The presence of histamine and acetylcholine in the spleen of the ox and the
      horse.

PMID- 16994064
TI  - The physiological activity of adenine compounds with especial reference to their
      action upon the mammalian heart.

PMID- 16994065
TI  - The anti-diuretic effect of the separated principles of the pituitary body.

PMID- 16994066
TI  - The action of ephedrine on the blood-sugar [with a note on its action on the
      denervated pupil of a cat].

PMID- 16994067
TI  - Sex differences in the cholesterol content of tissues.

PMID- 16994068
TI  - The source of expired CO(2) in decapitated, eviscerated cats.

PMID- 16994069
TI  - On the partial pressures of oxygen and carbon dioxide in arterial blood and
      alveolar air.

PMID- 16994070
TI  - The activity of the spleen during anaphylactic shock.

PMID- 16994071
TI  - The acid-base equilibrium in frog's muscle.

PMID- 16994072
TI  - Studies on water diuresis: Part II. The excretion of urine after hypophysectomy
      and decerebration.

PMID- 16994073
TI  - The replacement of depleted adrenaline in the suprarenals.

PMID- 16994074
TI  - The coronary circulation: III. The dependence of changes in the coronary blood
      flow on cardiac and local vascular factors.

PMID- 16994076
TI  - Observations on the standardization of the water-soluble, oestrus-producing
      hormone.

PMID- 16994075
TI  - The double heart-lung-kidney preparation.

PMID- 16994077
TI  - The influence of excision and treatment with saline on the pace-maker of the
      frog's heart.

PMID- 16994078
TI  - Some effects of emotion on the volume of the spleen.

PMID- 16994079
TI  - Quantitative observations on thyroxine and allied substances: II. Effects on the
      oxygen consumption of rats.

PMID- 16994080
TI  - The oxygen consumption of the auricles of the frog and of the tortoise.

PMID- 16994082
TI  - The effect of variations in the diastolic filling of the frog's ventricle upon
      the durations of the refractory period and the mechanical response.

PMID- 16994081
TI  - Action of ionic changes on the oxygen consumption of the frog's auricle.

PMID- 16994083
TI  - Reflex summation in the ipsilateral spinal flexion reflex.

PMID- 16994084
TI  - The source of co(2) expired and the site of its retention.

PMID- 16994085
TI  - The respiratory movements in gradual hydrocyanic acid poisoning.

PMID- 16994087
TI  - Foetal respiratory reflexes.

PMID- 16994086
TI  - Studies on water diuresis: Part III. A comparison of the excretion of urine by
      innervated and denervated kidneys perfused with the heart-lung preparation.

PMID- 16994088
TI  - On the influence of the extra-cardiac nerves upon sino-auricular conduction of
      the heart of Scyllium.

PMID- 16994089
TI  - The small intestine and gastric secretion: With special reference to Brunner's
      Glands.

PMID- 16994090
TI  - The relation between the rod and cone mechanisms in the after-effect of seen
      movement.

PMID- 16994091
TI  - The effect of temperature upon the absolute refractory period in nerve.

PMID- 16994092
TI  - A criticism of the Hill-Hartree method of curve analysis.

PMID- 16994093
TI  - The analysis of galvanometer curves.

PMID- 16994094
TI  - The temperatures in the tissues which accompany temperature sensations.

PMID- 16994095
TI  - The action of caffeine on the isolated kidney of the dog.

PMID- 16994096
TI  - The selective vaso-constrictor action of adrenaline.

PMID- 16994097
TI  - Studies on diffusion through surviving isolated intestine.

PMID- 16994098
TI  - The oxygen combining power of muscle haemoglobin.

PMID- 16994099
TI  - Alterations in the lactic acid content of the blood as a result of light
      exercise, and associated changes in the co(2)-combining power of the blood and in
      the alveolar co(2) pressure.

PMID- 16994100
TI  - The resistance of the pulmonary vascular bed.

PMID- 16994101
TI  - Sinus caroticus and respiratory reflexes: I. Cerebral blood flow and respiration.
      Adrenaline apnoea.

PMID- 16994102
TI  - Studies in muscular activity: VI. Response of several individuals to a fixed
      task.

PMID- 16994103
TI  - The energy expended in maintaining a muscular contraction.

PMID- 16994104
TI  - The relation between the mechanical and electrical response of the frog's heart.

PMID- 16994105
TI  - Studies of reflex activity in involuntary nervous system: II. Action of
      ergotamine on vaso-motor reflexes.

PMID- 16994106
TI  - The influence of vitamin a deficiency on the oestrous cycle of the rat: II.

PMID- 16994107
TI  - The effects produced by unilateral lumbar sympathectomy: I. Cutaneous
      temperatures and the limb musculature.

PMID- 16994108
TI  - The effects produced by unilateral lumbar sympathectomy: II. Muscle metabolism.

PMID- 16994109
TI  - The relative amounts of oestrin required to produce the various phenomena of
      oestrus.

PMID- 16994110
TI  - The isometric responses of mammalian muscles.

PMID- 16994111
TI  - The pulse wave velocity and extensibility of the brachial and radial artery in
      man.

PMID- 16994112
TI  - Tonus in mammalian unstriated muscle: I.

PMID- 16994114
TI  - Latency of after-images and interaction between the two retino-cerebral
      apparatuses in man.

PMID- 16994113
TI  - On the mechanism of sugar elimination in phlorrhizin glycosuria. A contribution
      to the filtration-reabsorption theory on kidney function.

PMID- 16994115
TI  - The heat production of smooth muscle.

PMID- 16994116
TI  - On the synergism between oestrin and oxytocin.

PMID- 16994117
TI  - The visco-elastic properties of frog's muscles.

PMID- 16994118
TI  - Action of adrenaline and related substances on respiration.

PMID- 16994119
TI  - Studies in the pulmonary circulation: III. The action of histamine.

PMID- 16994120
TI  - Notes on the knee extensor and the mirror myograph.

PMID- 16994122
TI  - Studies on ovulation: II. The effect of hypophysectomy on the formation of the
      corpus luteum.

PMID- 16994121
TI  - The measurement of red cell volume.

PMID- 16994123
TI  - Water diuresis.

PMID- 16994124
TI  - The selective vaso-constrictor action of pituitary pressor extract.

PMID- 16994125
TI  - Studies in water diuresis: Part IV. The changes in the concentration of
      electrolytes and colloids in the plasma of decerebrate dogs produced by the
      ingestion of water.

PMID- 16994126
TI  - The effect of adrenaline on muscle glycogen.

PMID- 16994127
TI  - The respiratory quotient of the eviscerated spinal cat.

PMID- 16994128
TI  - The delayed anaerobic heat production of stimulated muscle.

PMID- 16994129
TI  - Reactions of denervated voluntary muscle, and their bearing on the mode of action
      of parasympathetic and related nerves.

PMID- 16994130
TI  - On the nature of inhibition in the intestine.

PMID- 16994131
TI  - The automatic regulation of gastric acidity.

PMID- 16994133
TI  - The production of hypoglycaemia in rabbits by oral administration of precipitated
      insulin.

PMID- 16994132
TI  - The measurement of red cell volume: II. Alterations in cell volume in solutions
      of various tonicities.

PMID- 16994134
TI  - Interrelations of respiration and gastric secretion.

PMID- 16994135
TI  - The influence of the number of active fibres on the heat-tension ratios of
      striated muscle.

PMID- 16994136
TI  - Heat versus tension in relation to the problem of plurisegmental innervation.

PMID- 16994137
TI  - Recording of respiration of small animals.

PMID- 16994138
TI  - Influence of the aortic and carotid sinus nerves upon the height and form of the
      rise of blood-pressure produced by peripheral stimulation of the splanchnic
      nerve.

PMID- 16994139
TI  - The co(2) of the mixed venous blood of man.

PMID- 16994140
TI  - The sympathetic innervation of the stomach: I. The effect on the stomach of
      stimulation of the thoracic sympathetic trunk.

PMID- 16994141
TI  - Lactic acid formation and removal with change of blood reaction.

PMID- 16994142
TI  - The lactic acid content of the blood after muscular contraction under
      experimental conditions.

PMID- 16994143
TI  - The diffusion of creatine and urea through muscle.

PMID- 16994144
TI  - The effect of carbon dioxide on the circulation: Part I.

PMID- 16994145
TI  - Excitable substances in the nerve-muscle complex.

PMID- 16994146
TI  - The action of blood on acetylcholine.

PMID- 16994147
TI  - The inactivation of histamine.

PMID- 16994148
TI  - The carriage of carbon dioxide by blood.

PMID- 16994149
TI  - Studies on ovulation: III. Effect of vaginal anaesthesia on ovulation in the
      rabbit.

PMID- 16994150
TI  - The reversible loss of excitability in isolated amphibian voluntary muscle: 2. A
      comparison of the inexcitable condition obtained by different methods. Chronaxie
      and potassium diffusion.

PMID- 16994151
TI  - Selective absorption of carbohydrates.

PMID- 16994152
TI  - The vapour pressure of normal human blood.

PMID- 16994153
TI  - The absorption of calcium from the gall-bladder.

PMID- 16994154
TI  - The effect of insulin and other endocrine extracts on the cholesterol content of
      tissues.

PMID- 16994155
TI  - A reversed action of the chorda tympani on the venous outflow from the
      submaxillary gland.

PMID- 16994156
TI  - The relation between amplitude of contraction and rate of rhythm in the mammalian
      ventricle. (Including interpretation of the apparent indirect action of the vagus
      on amplitude of ventricular contraction).

PMID- 16994157
TI  - Studies on the intra-ocular pressure: Part I. The action of drugs on the vascular
      and muscular factors controlling the intra-ocular pressure.

PMID- 16994158
TI  - A method of ultra-filtration in vivo.

PMID- 16994159
TI  - An investigation into a possible nervous mechanism involved in the liberation of
      histamine.

PMID- 16994160
TI  - Studies on ovulation: IV. Induction of ovulation in the hypophysectomized rabbit
      by administration of anterior lobe extracts.

PMID- 16994161
TI  - Studies on ovulation: V. The action of ovulation-producing substance of urine of
      pregnancy on the hypophysectomized rabbit.

PMID- 16994162
TI  - Adaptations of the organism to changes in oxygen pressure.

PMID- 16994163
TI  - The response of a single end organ.

PMID- 16994164
TI  - Potential changes in the isolated brain stem of the goldfish.

PMID- 16994165
TI  - The initial and recovery heat production of vertebrate nerve.

PMID- 16994166
TI  - The relation of temperature to the pulse rate of the frog.

PMID- 16994167
TI  - The relation of temperature to the heart rate of the south african frog (Xenopus
      dactylethra).

PMID- 16994168
TI  - An analysis of the effect of cocaine on the actions of adrenaline and tyramine.

PMID- 16994169
TI  - The sympathetic innervation of the stomach: II. The effect of stimulation of the
      peri-arterial nerves on the stomach and small intestine.

PMID- 16994170
TI  - Some observations on the perfusion of the isolated kidney by a pump.

PMID- 16994171
TI  - On the creatine and phosphorus content of muscle.

PMID- 16994172
TI  - The influence of creatine on the excretion of phosphates by the kidney.

PMID- 16994173
TI  - The equilibrium between oxygen and haemoglobin: I. The oxygen dissociation curve
      of dilute blood solutions.

PMID- 16994174
TI  - The equilibrium between oxygen and haemoglobin: II. The oxygen dissociation
      curves of dilute solutions of horse haemoglobin.

PMID- 16994175
TI  - Studies on the intra-ocular pressure: Part II. The physico-chemical factors
      controlling the intra-ocular pressure.

PMID- 16994176
TI  - The influence of adrenaline on carbohydrate metabolism.

PMID- 16994177
TI  - Cardiac output and blood distribution.

PMID- 16994178
TI  - Adequate electrical stimuli for posture and movement.

PMID- 16994179
TI  - Concerning the amount of nitrogen gas in the tissues and its removal by breathing
      almost pure oxygen.

PMID- 16994180
TI  - The isoelectric point of sheep oxyhaemoglobin determined by titration curves with
      the glass electrode.

PMID- 16994181
TI  - On the influence of posture on kidney function.

PMID- 16994182
TI  - The metabolism of lactose: Part I. The occurrence of lactose in urine.

PMID- 16994183
TI  - Does muscular contraction affect the local blood supply in the absence of lactic
      acid formation?

PMID- 16994184
TI  - The nomenclature of the autonomic nervous system.

PMID- 16994185
TI  - The effect of temperature on the frequency of heart and respiration in the guinea
      pig and cat.

PMID- 16994186
TI  - The effect of exposure to cold on the pulse rate and respiration of man.

PMID- 16994187
TI  - The influence of increase of ureter pressure on the isolated mammalian kidney.

PMID- 16994188
TI  - The effect of evisceration on the respiratory metabolism of the decerebrate
      preparation.

PMID- 16994190
TI  - An apparatus for measuring transudation through a living membrane.

PMID- 16994189
TI  - Sugar tolerance and alcohol.

PMID- 16994191
TI  - On variations in the activity of the cardio-inhibitory centre.

PMID- 16994192
TI  - Relations between the actions of adrenaline, acetylcholine, and ions, on the
      perfused heart.

PMID- 16994193
TI  - The regeneration of visual purple: its relation to dark adaptation and night
      blindness.

PMID- 16994194
TI  - The analysis of the initial heat production of muscle.

PMID- 16994195
TI  - The effects of posture on the circulating blood volume.

PMID- 16994196
TI  - The effect of posture on the volume of the leg.

PMID- 16994197
TI  - Potential changes in the isolated nervous system of Dytiscus marginalis.

PMID- 16994198
TI  - Effects of high oxygen pressure on carbon dioxide transport, on blood and tissue
      acidity, and on oxygen consumption and pulmonary ventilation.

PMID- 16994199
TI  - The influence of venous pressure on the isolated mammalian kidney.

PMID- 16994200
TI  - The effects of oestrin on the pseudo-pregnant mouse.

PMID- 16994201
TI  - An unidentified depressor substance in certain tissue extracts.

PMID- 16994202
TI  - The influence of tissues and amino acids on the oxidation of adrenaline.

PMID- 16994203
TI  - The response of a muscle spindle during active contraction of a muscle.

PMID- 16994204
TI  - Some effects of carbonic acid on the character of human respiration.

PMID- 16994205
TI  - Properties of the peripheral vascular system and their relation to the systemic
      output.

PMID- 16994206
TI  - On the action of precipitated insulin administered by mouth.

PMID- 16994207
TI  - The deposition of dyes in the mammalian kidney.

PMID- 16994208
TI  - The oxygen consumption of the tortoise heart: its dependence upon diastolic
      volume and on the mechanical conditions of systole.

PMID- 16994209
TI  - The normal presence of alpha and gamma excitabilities in the nerve-muscle
      complex.

PMID- 16994210
TI  - Further observations relating to the physiological activity of adenine compounds.

PMID- 16994211
TI  - Age changes in the permeability of dog's enamel.

PMID- 16994212
TI  - Studies on the physiology of protein retention.

PMID- 16994213
TI  - A comparison of methods used for oxygenating blood in perfusion experiments.

PMID- 16994214
TI  - The composition and distribution of the fatty substances of the human subject.

PMID- 16994215
TI  - The glomerular pressure in the isolated mammalian kidney.

PMID- 16994216
TI  - Sensory discharges in single cutaneous nerve fibres.

PMID- 16994217
TI  - Response of tactile receptors to intermittent stimulation.

PMID- 16994218
TI  - A modified Krogh's bicycle ergometer.

PMID- 16994219
TI  - The effect of some factors upon the blood sugar of embryo chicks.

PMID- 16994220
TI  - On the existence of a most efficient speed in bicycle pedalling, and the problem
      of determining human muscular efficiency.

PMID- 16994221
TI  - The energy liberated in total exhaustion of frog's muscle.

PMID- 16994222
TI  - The metabolism of the isolated heart of the frog.

PMID- 16994223
TI  - Spinal, bulbar and decerebrate reflexes in the forelimb.

PMID- 16994224
TI  - The action of adrenaline on glycogen distribution in the cat.

PMID- 16994225
TI  - On the nature of the two types of response in the neuromuscular system of the
      crustacean claw.

PMID- 16994226
TI  - The part played by the thebesian vessels in the blood supply to the heart.

PMID- 16994227
TI  - Some observations on the effect of pressure in the carotid sinus upon the
      arterial pressure and upon the coronary circulation.

PMID- 16994228
TI  - Pseudomotor contractures after degeneration of the facial nerve.

PMID- 16994229
TI  - The behaviour of liver glycogen in experimental animals: I. Methods: the effect
      of ether and amytal.

PMID- 16994230
TI  - The behaviour of liver glycogen in experimental animals: II. Glycogen recovery
      after decapitation and decerebration.

PMID- 16994231
TI  - The variations in the acidity of the gastric juice during secretion.

PMID- 16994232
TI  - Observations on the assay of the comb-growth promoting hormone.

PMID- 16994233
TI  - The sympathetic innervation of the stomach: III. The interaction of the vagus and
      sympathetic nerves.

PMID- 16994234
TI  - The control of the glomerular pressure by vascular changes within the isolated
      mammalian kidney, demonstrated by the actions of adrenaline.

PMID- 16994236
TI  - The state of water in mammalian tissues.

PMID- 16994235
TI  - The absorption of glucose from the alimentary canal.

PMID- 16994237
TI  - Has the muscular substance a longer chronaxie than the nervous substance?

PMID- 16994238
TI  - The growth effect and toxicity of some halogen derivatives of the isomeric
      monohydroxyphenylalanines.

PMID- 16994239
TI  - On electric stimulation of muscle through ringer's solution.

PMID- 16994240
TI  - The after-image of black.

PMID- 16994241
TI  - The measurement of red cell volume: III. Alterations of cell volume in extremely
      hypotonic solutions.

PMID- 16994242
TI  - The influence of the vagus nerves on the secretions of insulin.

PMID- 16994243
TI  - The protein content and osmotic pressure in serum of young animals.

PMID- 16994244
TI  - On the state of CO(2) in blood and haemoglobin solutions, with an appendix on
      some osmotic properties of glycine in solution.

PMID- 16994245
TI  - The relation of gastric function to the chemical composition of the blood.

PMID- 16994246
TI  - The rate of blood flow through cyanosed skin.

PMID- 16994247
TI  - The rate of gas exchange between blood cells and serum.

PMID- 16994248
TI  - On the effect of diathermy on blood volume.

PMID- 16994249
TI  - The tolerance of normal rabbits to intravenous injection of glucose.

PMID- 16994250
TI  - The elimination of urea by the mammalian kidney.

PMID- 16994251
TI  - Action of narcotics on the conduction of nerve impulses from a single end-organ.

PMID- 16994252
TI  - The effect of pulse pressure upon the coronary blood flow.

PMID- 16994253
TI  - The buffer substances of the gastric juice, and their relation to gastric mucus.

PMID- 16994254
TI  - The coronary circulation in the isolated perfused heart.

PMID- 16994255
TI  - The latent period of skeletal muscle.

PMID- 16994256
TI  - The course of the vaso-constrictor nerves to the periphery.

PMID- 16994257
TI  - Observations on the time taken for corpuscles to traverse the liver.

PMID- 16994259
TI  - The effect of chicago blue and chlorazol blue on the clotting time of the blood
      and on ovulation in the rabbit.

PMID- 16994258
TI  - Studies on the physiology of reproduction: I. The effect of thymectomy and of
      season on the age and weight of puberty in the female rat.

PMID- 16994260
TI  - The body temperature in rats on normal and deficient diets: Preliminary report.

PMID- 16994261
TI  - The vagus influences giving rise to the phenomena accompanying expansion and
      collapse of the lungs.

PMID- 16994262
TI  - Discharges in mammalian sympathetic nerves.

PMID- 16994263
TI  - The significance of the pituitary in parturition.

PMID- 16994264
TI  - Nucleic acid derivatives and the heart beat.

PMID- 16994265
TI  - Some effects of carbonic acid in high concentration on respiration.

PMID- 16994266
TI  - The metabolism of postural and phasic contractions of the quadriceps of the cat.

PMID- 16994267
TI  - Studies on ovulation: VI. Relative importance of concentration and absolute
      amount of the ovulation-producing hormone.

PMID- 16994268
TI  - The sympathetic innervation of the stomach: IV. Reversal of sympathetic action by
      luminal.

PMID- 16994269
TI  - Phosphate in tumours and muscle.

PMID- 16994270
TI  - Studies on the physiology of reproduction: II. The effect of thymectomy on the
      age of puberty in the male rat.

PMID- 16994271
TI  - Studies on the physiology of reproduction: III. The effect of thymectomy on
      fertility in the rat.

PMID- 16994272
TI  - The renal circulation rate in the rabbit.

PMID- 16994273
TI  - The delayed anaerobic heat production of stimulated muscle.

PMID- 16994274
TI  - Nerve supply to Lucas's alpha substance.

PMID- 16994275
TI  - The effect of washing upon the resistance of erythrocytes to hypotonic solutions.

PMID- 16994276
TI  - A vaso-constrictor action of acetylcholine on the rabbit's pulmonary circulation.

PMID- 16994277
TI  - The action of cyanide on the isolated mammalian kidney.

PMID- 16994278
TI  - Rhythmical contraction of the spleen.

PMID- 16994279
TI  - Cause of rhythmical contraction of the spleen.

PMID- 16994280
TI  - Undulatory changes of blood-pressure.

PMID- 16994281
TI  - The action of the splanchnic nerves on the spleen.

PMID- 16994282
TI  - Observations on the structure and function of certain blood vessels in the
      spleen.

PMID- 16994283
TI  - The reappearance of glycogen in the muscles of the decerebrate cat after its
      removal during tetanic contraction.

PMID- 16994284
TI  - The control of circulation through the liver.

PMID- 16994285
TI  - The influence of work on the calorigenic action of thyroxine.

PMID- 16994286
TI  - Some foetal blood-pressure reactions.

PMID- 16994287
TI  - The effect of thyroid feeding on the oxygen consumption of the heart and of other
      tissues.

PMID- 16994288
TI  - Regional variations in sensitivity to flicker.

PMID- 16994289
TI  - Lapicque's canonical strength duration curve.

PMID- 16994290
TI  - The effect of length on the resting metabolism of muscle.

PMID- 16994291
TI  - The thermo-elastic properties of muscle.

PMID- 16994292
TI  - The changes in the co(2) pressure and hydrogen ion concentration of the arterial
      blood of man which are associated with hyperpnoea due to co(2).

PMID- 16994293
TI  - The effects of intestinal rhythm on general blood-pressure.

PMID- 16994294
TI  - The staircase phenomenon in ventricular muscle.

PMID- 16994295
TI  - State of the flexor reflex in paraplegic dog and monkey respectively.

PMID- 16994296
TI  - The role of the pituitary gland in pregnancy and parturition: I. Hypophysectomy.

PMID- 16994297
TI  - The influence of insulin on the liver glycogen of the common grey australian
      "opossum" (Trichosurus).

PMID- 16994298
TI  - The influence of temperature in the frog: (1) On the circulation, and (2) On the
      circulatory effects of adrenaline and of sodium nitrite.

PMID- 16994299
TI  - Note on the effect of age on the response of immature mice to urine of pregnancy.

PMID- 16994300
TI  - Further observations on the effects of some component of crude lecithine on
      depancreatized animals.

PMID- 16994301
TI  - The effect of lecithine on fat deposition in the liver of the normal rat.

PMID- 16994302
TI  - The influence of muscular work on protein metabolism.

PMID- 16994303
TI  - Changes in the blood composition of unanaesthetized rabbits following the
      ingestion of water and saline: With special reference to the distribution of
      fluid between plasma and corpuscles and to the relationship between blood
      composition and diuresis.

PMID- 16994304
TI  - The responses of the batrachian alimentary canal to autonomic drugs. Rana and
      Bufo arecoline.

PMID- 16994305
TI  - Physiological leucocytosis: The variation in the leucocyte count during rest and
      exercise, and after the hypodermic injection of adrenaline.

PMID- 16994306
TI  - Normal respiration and the influence of the vagi.

PMID- 16994307
TI  - Creatine and phosphorus compounds in malignant tumours.

PMID- 16994308
TI  - On vaso-dilator fibres in the sympathetic, and on the effect of circulating
      adrenaline in augmenting the vascular response to sympathetic stimulation.

PMID- 16994309
TI  - Identification of the gamma excitability in muscle.

PMID- 16994310
TI  - The effect of the injection of blood on the urea in blood and urine.

PMID- 16994311
TI  - The lactic acid metabolism of frog's muscle poisoned with iodoacetic acid: I. The
      lactic acid metabolism of anaerobic iodoacetate muscle. II. The lactic acid
      metabolism of aerobic iodoacetate muscle.

PMID- 16994312
TI  - Reversal of the gastric vagus.

PMID- 16994313
TI  - Chloride and vapour-pressure relations in the secretory activity of the gills of
      the eel.

PMID- 16994314
TI  - The portal circulation: I. The action of adrenaline and pituitary pressor
      extract.

PMID- 16994315
TI  - The influence of shortening on the heat production of the frog's gastrocnemius.

PMID- 16994316
TI  - The analysis of the delayed heat production of muscle.

PMID- 16994317
TI  - Pulmonary oedema in the cat heart-lung preparation.

PMID- 16994318
TI  - Inhibition of the anaphylactic reaction by congo red.

PMID- 16994319
TI  - The carbohydrate metabolism of the isolated heart of the frog.

PMID- 16994320
TI  - The anaerobic activity of the isolated frog's heart.

PMID- 16994321
TI  - Phosphagen in the perfused heart of the frog.

PMID- 16994322
TI  - The interdependence of gastric secretion and the CO(2) content of the blood.

PMID- 16994323
TI  - The influence of the parathyroid on the metabolism of creatine and phosphoric
      acid: Part I. Phosphate excretion after injections of creatine and parathormone.
      Part II. Regulation of creatine phosphate after thyroparathyroidectomy, etc.

PMID- 16994324
TI  - The influence of toxaemia on carbohydrate metabolism.

PMID- 16994325
TI  - The effects of the components of lecithine upon deposition of fat in the liver.

PMID- 16994326
TI  - Observations on extracts of beef adrenal cortex and elasmobranch interrenal body.

PMID- 16994327
TI  - Deterioration of fibrinogen and thrombin.

PMID- 16994328
TI  - The influence of electrolytes on the function of the intestinal mucosa.

PMID- 16994329
TI  - Identification of Lucas's alpha excitability.

PMID- 16994330
TI  - The actions of adrenaline and of acetylcholine on the isolated pulmonary vessels
      and azygos vein of the dog.

PMID- 16994331
TI  - The functions of the great splanchnic nerves.

PMID- 16994333
TI  - The effect of fatigue on end-plate delay.

PMID- 16994332
TI  - Studies concerning the alimentary absorption of water and tissue hydration in
      relation to diuresis.

PMID- 16994334
TI  - The regulation of the pyloric sphincter.

PMID- 16994335
TI  - Factors influencing the actions of corpus luteum extracts on the rabbit's uterus.

PMID- 16994336
TI  - The relation of athletic status to the pulse rate, in men and women.

PMID- 16994337
TI  - "Postural reversal" in peripheral preparations.

PMID- 16994338
TI  - Researches on the contracture of skeletal muscle.

PMID- 16994340
TI  - The action of pituitary posterior lobe extracts on different parts of the
      circulatory system.

PMID- 16994339
TI  - Excitability of the single fibre nerve-muscle complex.

PMID- 16994341
TI  - The resting heat production of nerve.

PMID- 16994342
TI  - The function of the adrenal medulla.

PMID- 16994343
TI  - The supernormal phase in muscular contraction.

PMID- 16994344
TI  - The effects of injections of extracts of adrenal cortex on the development and
      sex functions of the albino mouse.

PMID- 16994345
TI  - The refractory period of mammalian cardiac muscle, with especial reference to
      purkinje tissue.

PMID- 16994346
TI  - The action of some amines related to adrenaline: I. Methoxy-phenylethylamines.

PMID- 16994347
TI  - Studies on the physiology of reproduction: IV. Changes in the adrenal gland of
      the female rat associated with the oestrous cycle.

PMID- 16994348
TI  - Retrograde polarization, a theory of systematic errors in measurements of
      muscular chronaxie through ringer's fluid or with large electrodes.

PMID- 16994350
TI  - An anti-growth principle derived from the parathyroid gland.

PMID- 16994349
TI  - Studies concerning the alimentary absorption of water and tissue hydration in
      relation to diuresis.

PMID- 16994351
TI  - The effect of parathyroid hormone and of irradiated ergosterol on calcium and
      phosphorous metabolism in the rat.

PMID- 16994352
TI  - Inorganic sulphate excretion by the human kidney.

PMID- 16994353
TI  - A study of the influence of adrenaline on the systemic blood flow.

PMID- 16994354
TI  - The action of histamine on the respiratory tract.

PMID- 16994355
TI  - "Chloride secreting cells" in the gills of fishes, with special reference to the
      common eel.

PMID- 16994356
TI  - The diuretic action of alcohol and its relation to pituitrin.

PMID- 16994357
TI  - THE BEHAVIOUR OF LIVER GLYCOGEN IN EXPERIMENTAL ANIMALS: III. THE RELATIONSHIP OF
      BLOOD PHOSPHORUS TO LIVER GLYCOGEN AND BLOOD GLUCOSE IN THE DECAPITATE CAT.

PMID- 16994358
TI  - The behaviour of liver glycogen in experimental animals: IV. The effect of some
      anaesthetics.

PMID- 16994359
TI  - The behaviour of liver glycogen in experimental animals: V. Some factors
      affecting liver glycogen recovery in the decapitate cat.

PMID- 16994360
TI  - The effect of some accidental lesions on the size of the spleen.

PMID- 16994361
TI  - Alterations in the size of the denervated spleen related to pregnancy.

PMID- 16994362
TI  - The volume of blood in the uterus during pregnancy.

PMID- 16994363
TI  - Observations on the proximal portion of the exteriorized colon.

PMID- 16994364
TI  - The optimum temperature for investigations on the frog's circulation.

PMID- 16994365
TI  - The role of lactic acid in nerve activity.

PMID- 16994366
TI  - A comparison of the properties of certain tissue extracts having depressor
      effects.

PMID- 16994368
TI  - The metabolism of lactose: Part II. The blood sugar during lactation.

PMID- 16994367
TI  - Double vagotomy in relation to respiration.

PMID- 16994369
TI  - A negative phase in the heat production of muscle.

PMID- 16994370
TI  - Observations on panting.

PMID- 16994371
TI  - The pressure of aqueous vapour in the alveolar air.

PMID- 16994372
TI  - Studies in muscular activity: VII. Factors limiting the capacity for work.

PMID- 16994373
TI  - Physiological leucocytosis: II. Post-prandial leucocytosis and Widal's
      haemoclasic test for hepatic efficiency.

PMID- 16994374
TI  - The action of adrenaline upon the cardiac vagus centres.

PMID- 16994375
TI  - Phlorrhizin diabetes in fasting or fed hypophysectomized dogs.

PMID- 16994376
TI  - Ketosis in the pancreatic and phlorrhizin diabetes of hypophysectomized dogs.

PMID- 16994377
TI  - The blood cholesterol in anaesthesia.

PMID- 16994378
TI  - The heat production of crustacean nerve.

PMID- 16994380
TI  - Studies on the physiology of reproduction: V. The adrenal cortex in pregnancy and
      lactation.

PMID- 16994379
TI  - The localization of the action of drugs on the pulmonary vessels of dogs and
      cats.

PMID- 16994381
TI  - The differential pharmacology of the inferior vena cava of some mammals.

PMID- 16994382
TI  - The measurement of red cell volume: IV. Alterations in cell volume in hypotonic
      plasma.

PMID- 16994383
TI  - The investigation of the toxic effects of large amounts of sugar in the blood.

PMID- 16994384
TI  - The rate of blood flow and gaseous metabolism of the uterus during pregnancy.

PMID- 16994385
TI  - The components of the retinal action potential in mammals and their relation to
      the discharge in the optic nerve.

PMID- 16994386
TI  - Experiments on the nature of the labile role of sulphur in metabolism.

PMID- 16994388
TI  - Observations on sensation: The sensory functions of the skin for touch and pain.

PMID- 16994387
TI  - The antagonistic effect of alcohol on pituitrin hyperglycaemia.

PMID- 16994389
TI  - Single-shock excitation and inhibition of contralateral extension in the spinal
      cat.

PMID- 16994390
TI  - Respiration of isolated gill tissue of the eel.

PMID- 16994391
TI  - The mucus factor in the automatic regulation of the acidity of the gastric
      contents.

PMID- 16994393
TI  - The central and the reflex mechanism of panting.

PMID- 16994392
TI  - The histamine-histaminase system in the isolated perfused kidney-lung
      preparation.

PMID- 16994394
TI  - Lapicque's theory of curarization.

PMID- 16994396
TI  - The excretion of protein by the mammalian kidney.

PMID- 16994395
TI  - The effect of insulin on the respiratory quotient, oxygen consumption, sugar
      utilization, and glycogen synthesis in the normal mammalian heart in hyper- and
      hypoglycaemia.

PMID- 16994397
TI  - The portal circulation: II. The action of acetylcholine.

PMID- 16994398
TI  - The nervous control of the caudal region of the large bowel in the cat.

PMID- 16994399
TI  - The influence of oxygen pressure on the metabolism of the isolated cold-blooded
      heart.

PMID- 16994400
TI  - The gastric fibres of the vagus nerve.

PMID- 16994401
TI  - Nerve endings in mammalian muscle.

PMID- 16994402
TI  - The effect of activity on the form of the muscle twitch.

PMID- 16994403
TI  - Studies on histamine hypotension.

PMID- 16994404
TI  - The influence of foodstuffs on the rate of urinary acid excretion.

PMID- 16994405
TI  - The effect of hysterectomy on the oestrous cycle of the ferret.

PMID- 16994406
TI  - The action of strychnine on hering-breuer reflexes.

PMID- 16994407
TI  - Ergotamine and the effect of adrenaline on blood lactate.

PMID- 16994408
TI  - The rate of water absorption in man and the relationship of the water load in
      tissues to diuresis.

PMID- 16994409
TI  - The effect of water drinking on the blood composition of human subjects in
      relation to diuresis.

PMID- 16994410
TI  - The influence of posterior pituitary hormone on the absorption and distribution
      of water in man.

PMID- 16994411
TI  - Note on the subcutaneous absorption of oils by rats and mice, with special
      reference to the assay of oestrin.

PMID- 16994412
TI  - The effect of sympathetic nerve stimulation on the power of contraction of
      skeletal muscle.

PMID- 16994413
TI  - Observations on the pumping action of the heart.

PMID- 16994414
TI  - The decerebrate rat.

PMID- 16994415
TI  - The responses to stimulation of the caudal end of the large bowel in the cat.

PMID- 16994416
TI  - Action potentials in sympathetic nerves, elicited by stimulation of frog's
      viscera.

PMID- 16994417
TI  - The efficiency of isolated muscle in relation to the degree of aerobic activity.

PMID- 16994418
TI  - The action of ether on the sympathetic system.

PMID- 16994419
TI  - Rhythmic activity in skeletal muscle fibres.

PMID- 16994420
TI  - Glycogen synthesis in the small intestine.

PMID- 16994421
TI  - The re-synthesis of creatinephosphoric acid in frog's muscle poisoned with
      iodoacetic acid.

PMID- 16994422
TI  - On the supposed inhibitory action of the auricles on the amplitude of the
      ventricular contractions in the heart of the frog.

PMID- 16994423
TI  - The reactivity and activity of the rabbit's uterus during pregnancy, parturition
      and the puerperium.

PMID- 16994424
TI  - Theories of muscular contraction.

PMID- 16994425
TI  - The polymorphonuclear-lymphocyte ratio at an altitude of 5750 feet.

PMID- 16994426
TI  - The apparent viscosity of blood flowing in the isolated hindlimb of the dog, and
      its variation with corpuscular concentration.

PMID- 16994427
TI  - The adrenals and anaesthetic hyperglycaemia.

PMID- 16994428
TI  - Alpha and gamma curves in slow muscles.

PMID- 16994429
TI  - The influence of ammonium chloride on adaptation to low barometric pressures.

PMID- 16994430
TI  - The effects of cholesterol and choline on deposition of liver fat.

PMID- 16994431
TI  - Observations on the retinal action potential with especial reference to the
      response to intermittent stimulation.

PMID- 16994432
TI  - Size changes in the seminal vesicles of the mouse during development and after
      castration.

PMID- 16994433
TI  - The effect of the intravenous administration of water upon the rate of urine
      formation.

PMID- 16994434
TI  - On the presence of "novadrenine" in suprarenal extracts.

PMID- 16994435
TI  - An apparatus for the production of finely dispersed emulsions, and the rate of
      digestion of fat by lipase in relation to the surface area.

PMID- 16994436
TI  - The effect of gonadectomy on the adrenal, thyroid, and pituitary glands.

PMID- 16994437
TI  - Reversible inexcitability of tactile endings in skin injury.

PMID- 16994438
TI  - The influence of temperature on the rate of excretion of phenolsulphonephthalein
      in the frog.

PMID- 16994439
TI  - The histological changes in the bone responsible for the action of parathyroid
      hormone on the calcium metabolism of the rat.

PMID- 16994440
TI  - Capacity of the uterus of the rabbit to respond to prolonged luteal activity.

PMID- 16994441
TI  - Diffusion of inorganic phosphate into and out of the skeletal muscles and bones
      of the frog.

PMID- 16994442
TI  - Carotid sinus reflexes. Influence of central blood-pressure and blood supply on
      respiratory and vaso-motor centres.

PMID- 16994443
TI  - The action of veratrine, curare and strychnine on the response of medullated
      nerve.

PMID- 16994444
TI  - The effect of quaternary ammonium salts upon nerve: Preliminary communication.

PMID- 16994445
TI  - The reactivity and activity of the human uterus at various stages of pregnancy
      and at parturition.

PMID- 16994446
TI  - Choline and liver fat in diabetic dogs.

PMID- 16994447
TI  - The physiological significance of weber's law and colour contrast in vision.

PMID- 16994449
TI  - A simple photoelectric colorimeter.

PMID- 16994448
TI  - The effect of oestrin on the reactivity and spontaneous activity of the rabbit's
      uterus.

PMID- 16994450
TI  - The kinetics of blood pigments: haemocyanin and haemoglobin.

PMID- 16994451
TI  - Ovulation after blood dilution and cross-circulation.

PMID- 16994452
TI  - A note on the retinal action potential of the human eye.

PMID- 16994453
TI  - Albuminuria in the normal male rat.

PMID- 16994454
TI  - The diffusion of lactate into and from muscle.

PMID- 16994455
TI  - An isolated mammalian heart preparation capable of performing work for prolonged
      periods.

PMID- 16994456
TI  - The influence of the parathyroid on the metabolism of creatine and phosphoric
      acid.

PMID- 16994458
TI  - The extra-uterine survival of spermatozoa.

PMID- 16994457
TI  - The excretion of prolan after intravenous injection into the rabbit.

PMID- 16994459
TI  - Histamine in canine gastric tissues.

PMID- 16994460
TI  - The effect of atropine on adrenaline hyperglycaemia in rabbits decerebrated
      anterior to the pons.

PMID- 16994461
TI  - The alleged occurrence of acetylcholine in ox blood.

PMID- 16994462
TI  - Choline esters in tissue extracts.

PMID- 16994463
TI  - Insulin and adrenaline.

PMID- 16994464
TI  - The normal behaviour of the isolated uterus of the guinea-pig, and its reactions
      to oestrin and oxytocin.

PMID- 16994465
TI  - The effect of the cardiac contraction upon the coronary flow.

PMID- 16994466
TI  - Afferent impulses in the vagus and their effect on respiration.

PMID- 16994467
TI  - The renal elimination of injected urea and creatinine.

PMID- 16994468
TI  - The control of the insulin output of the pancreas.

PMID- 16994469
TI  - The outline method for investigating gastric motility.

PMID- 16994470
TI  - Influence of osmotic pressure upon the emptying time of the stomach.

PMID- 16994471
TI  - Blood lactic acid in man during rest.

PMID- 16994472
TI  - Adrenaline in the suprarenal medulla.

PMID- 16994473
TI  - The influence of certain factors upon the volume of the intrathoracic venae
      cavae.

PMID- 16994474
TI  - Effect of breathing on the intra-abdominal pressure.

PMID- 16994475
TI  - The electrical resistance of stimulated muscle.

PMID- 16994476
TI  - A revised analysis of the initial heat production of muscle.

PMID- 16994477
TI  - The effect of ions on the cutaneous sensory endings of the frog.

PMID- 16994478
TI  - The respiratory quotient of the eviscerate cat.

PMID- 16994479
TI  - Carbohydrate metabolism and the effect of decapitation and decerebration under
      nitrous oxide anaesthesia.

PMID- 16994480
TI  - Nerves and nerve endings in the visceral pleura of the cat.

PMID- 16994481
TI  - The effect on the reproductive organs of the rat of prolonged treatment with
      ovary-stimulating substances.

PMID- 16994482
TI  - The utilization of blood sugar and lactate by the heart-lung preparation.

PMID- 16994483
TI  - The formation of liver glycogen in the cat, under various conditions, following
      infusion of ammonium lactate.

PMID- 16994484
TI  - Influence of the autonomic nerves on alimentary hyperglycaemia and on the
      absorption of glucose.

PMID- 16994485
TI  - Examination of the pulmonary circulation with the microscope.

PMID- 16994486
TI  - Induction of ovulation in the unmated oestrous ferret.

PMID- 16994487
TI  - The relationship of azo dyes to the coagulation of blood.

PMID- 16994488
TI  - The effect of parathyroid hormone and of irradiated ergosterol upon the calcium
      content of the parotid saliva of the dog.

PMID- 16994489
TI  - Carbonic anhydrase. Its preparation and properties.

PMID- 16994490
TI  - The state of carbon dioxide in blood.

PMID- 16994491
TI  - The occurrence of carbonic anhydrase in lower marine animals.

PMID- 16994492
TI  - The growth and regression of follicles in the oestrous rabbit.

PMID- 16994493
TI  - The respiratory quotient, oxygen consumption and glycogen content of the
      mammalian heart in aglycaemia.

PMID- 16994494
TI  - Relation of the pituitary gland to the action of insulin and adrenaline.

PMID- 16994495
TI  - A comparison of foetal and maternal haemoglobins in the goat.

PMID- 16994496
TI  - The effect of muscle length on the energy for maintenance of tension.

PMID- 16994497
TI  - The phosphorus distribution in resting fly muscle.

PMID- 16994498
TI  - The excretion of non-metabolized sugars by the mammalian kidney.

PMID- 16994499
TI  - The excretion of cyanol by the mammalian kidney.

PMID- 16994500
TI  - Influences which affect the form of the respiratory cycle, in particular that of
      the expiratory phase.

PMID- 16994502
TI  - The behaviour of the liver glycogen during decerebration hyperglycaemia and the
      influence of atropine and of ergotamine on this condition.

PMID- 16994501
TI  - The submaximal responses of the single muscle fibre.

PMID- 16994503
TI  - The effect of diet, of insulin and of thyroxine upon the adrenaline content of
      the suprarenal glands.

PMID- 16994504
TI  - The correlation between the action of insulin and adrenaline upon the muscle and
      liver glycogen.

PMID- 16994505
TI  - The effect of splanchnotomy and of phlorrhizin on decerebration hyperglycaemia.

PMID- 16994506
TI  - The influence of vagal stimulation upon conduction through the branches of the a.
      v. bundle in the dog.

PMID- 16994507
TI  - The biological significance of the linkages in adenosine triphosphoric acid.

PMID- 16994508
TI  - The effect of insulin and other factors on iodo-acetate hyperglycaemia.

PMID- 16994509
TI  - The carbohydrate metabolism of the kidney.

PMID- 16994510
TI  - On the occurrence of two kinds of haemoglobin in normal human blood.

PMID- 16994511
TI  - Some forms of apparatus for the equilibration of blood.

PMID- 16994512
TI  - The effect of duration of work on the efficiency of muscular work in man.

PMID- 16994513
TI  - Action of acetylcholine on the brain and its occurrence therein.

PMID- 16994514
TI  - Estimation of fibrinogen and thrombin.

PMID- 16994515
TI  - The vaso-dilator action of adrenaline.

PMID- 16994516
TI  - "Inhibition" in medullated nerve.

PMID- 16994518
TI  - Glycogen storage and laevulose tolerance.

PMID- 16994517
TI  - The anaerobic breakdown of carbohydrate in the isolated ventricle of the frog.

PMID- 16994519
TI  - The carbon dioxide balance between the maternal and foetal bloods in the goat.

PMID- 16994520
TI  - A spectroscopic method for the study of haemoglobin in dilute solutions.

PMID- 16994521
TI  - The electrical responses of light- and dark-adapted frogs' eyes to rhythmic and
      continuous stimuli.

PMID- 16994522
TI  - An adrenaline-like action in extracts from the prostatic and related glands.

PMID- 16994523
TI  - Neuro-muscular isochronism and chronological theory of curarization.

PMID- 16994524
TI  - Dietetic factors influencing the glucose tolerance and the activity of insulin.

PMID- 16994526
TI  - The effect of ligation of posterior coronary vessels on the electrocardiogram in
      experimental bundle-branch block.

PMID- 16994525
TI  - The oxytocic property of the blood of the cow.

PMID- 16994528
TI  - The adrenals and glucose tolerance.

PMID- 16994527
TI  - The humoral control of the secretion by the submaxillary gland of the cat
      following chorda stimulation.

PMID- 16994529
TI  - Modifications in the use of the glass electrode for the determination of the pH
      of venous blood.

PMID- 16994531
TI  - A micro method for the determination of base by electrodialysis.

PMID- 16994530
TI  - The action of insulin on the r.q., oxygen utilization, CO(2) production and sugar
      utilization in the mammalian diabetic heart.

PMID- 16994532
TI  - A method for determining in animals the alimentary absorption time for water, the
      abdomen remaining intact.

PMID- 16994533
TI  - The pituitary gland in relation to polyuria and to water diuresis.

PMID- 16994534
TI  - The autolysis of the placental glycogen.

PMID- 16994535
TI  - Reflexes in the triceps extensor preparation of the forelimb.

PMID- 16994536
TI  - The effects of hypothalamic stimulation on gastric motility.

PMID- 16994537
TI  - Conduction in the cervical sympathetic.

PMID- 16994538
TI  - The repetition of certain experiments on which Molitor and Pick base their water
      centre hypothesis, and the effect of afferent nerve stimuli on water diuresis.

PMID- 16994539
TI  - Energy expenditure in walking and running.

PMID- 16994540
TI  - A device for estimating blood-pressure in the rabbit.

PMID- 16994542
TI  - Reciprocal activity of the cornua and cervix uteri of the goat.

PMID- 16994541
TI  - The resistance of arterial walls and its effect on blood-pressure readings.

PMID- 16994543
TI  - Increase of pressure in veins to level of arterial pressure caused by
      constricting the limb in which the venous pressure is recorded.

PMID- 16994544
TI  - The mechanism of the nervous discharge of adrenaline.

PMID- 16994545
TI  - The chemical transmitter at synapses in a sympathetic ganglion.

PMID- 16994546
TI  - The chemical transmitter of vagus effects to the stomach.

PMID- 16994547
TI  - The assay of the ovulation-producing substance.

PMID- 16994548
TI  - The absolute value of the isometric heat coefficient determined by means of high
      frequency calibration of the living muscle.

PMID- 16994549
TI  - The significance of the luteal action on the uterine muscle in the maintenance of
      gestation and initiation of parturition.

PMID- 16994550
TI  - The production of cardiac irregularities by excitation of the hypothalmic
      centres.

PMID- 16994551
TI  - The "Wever and Bray phenomenon." A study of the electrical response in the
      cochlea with especial reference to its origin.

PMID- 16994553
TI  - The action of some amines related to adrenaline, methoxyphenyl
      methoxyethylamines.

PMID- 16994552
TI  - Choline and the dietary production of fatty livers.

PMID- 16994554
TI  - Effects of respiration upon the venae cavae of certain mammals, as studied by
      means of x-ray cinematography.

PMID- 16994555
TI  - The interpretation of potential waves in the cortex.

PMID- 16994556
TI  - The formation of the corpus luteum is dependent on the anterior pituitary lobe,
      and not on the maturing ovum. The fertilized ovum and hormones.

PMID- 16994557
TI  - Pilocarpine and gastric anacidity in monkeys.

PMID- 16994558
TI  - Uterine reactivity and activity in the mouse at various stages of the sex cycle.

PMID- 16994560
TI  - Changes in clotting time during and after exercise in dogs.

PMID- 16994559
TI  - Studies on the physiology of the thyreotropic hormone of the anterior pituitary.

PMID- 16994561
TI  - The alleged occurrence of acetylcholine in normal ox blood.

PMID- 16994562
TI  - The chemical transmission of secretory impulses to the sweat glands of the cat.

PMID- 16994563
TI  - A magnetic blood oxygenator.

PMID- 16994564
TI  - A spectroscopic comparison of foetal and maternal blood of the rabbit and goat.

PMID- 16994565
TI  - Acetylcholine in ox and dog blood.

PMID- 16994566
TI  - Utilization of blood sugar and formation of lactic acid by the lungs.

PMID- 16994567
TI  - The effect of water drinking, mineral starvation and salt administration on the
      total osmotic pressure of the blood in man, chiefly in relation to the problems
      of water absorption and water diuresis.

PMID- 16994568
TI  - The fate of carotene introduced into the circulation.

PMID- 16994569
TI  - A physiological study of phosphagen in plain muscle.

PMID- 16994571
TI  - On the mechanism of the autacoid function of parasympathetic nerves.

PMID- 16994570
TI  - The after effects of sudden changes in stimulation rate under different
      conditions of anaesthesia.

PMID- 16994572
TI  - Action of insulin on the heart and blood-pressure.

PMID- 16994573
TI  - The blood volume and oxygen capacity of the foetal blood in the goat.

PMID- 16994574
TI  - A study of the mistakes in colour matching made by persons with defective colour
      vision.

PMID- 16994575
TI  - Unisegmental reflexes in the dogfish.

PMID- 16994576
TI  - The effect of prolonged hard muscular work on sulphur and nitrogen metabolism.

PMID- 16994577
TI  - The efficiency and performance of a vegetarian racing cyclist under different
      dietary conditions.

PMID- 16994578
TI  - The efficiency of bicycle pedalling in the trained subject.

PMID- 16994579
TI  - The efficiency of bicycle pedalling.

PMID- 16994581
TI  - Further experiments on vagal inhibition of the heart beat.

PMID- 16994580
TI  - The action of a single vagal volley on the rhythm of the heart beat.

PMID- 16994582
TI  - Changes in the "efficiency" of muscular contraction during a series of twitches
      in nitrogen.

PMID- 16994583
TI  - Asphyxial arrest of the isolated frog's ventricle.

PMID- 16994584
TI  - A note on the recovery heat of frog's muscle at high temperature.

PMID- 16994585
TI  - Does vagus stimulation cause an increase in the acetylcholine content of heart
      muscle?

PMID- 16994586
TI  - The humoral control of the secretion by the submaxillary gland of the cat
      following sympathetic stimulation.

PMID- 16994587
TI  - A study of chemical changes associated with muscular contraction in normal and
      adrenalectomized animals.

PMID- 16994588
TI  - Strength-duration curves for repetitive stimulation of medullated nerve.

PMID- 16994589
TI  - A physical analysis of the relation between threshold and interpolar length in
      the electric excitation of medullated nerve.

PMID- 16994590
TI  - The rate of development and spread of electrotonus.

PMID- 16994591
TI  - A case of deficient acclimatization to low oxygen pressure.

PMID- 16994592
TI  - The relation of the central nervous system to the increase in systemic flow
      produced by occlusion of the thoracic aorta.

PMID- 16994594
TI  - The action of adrenaline on serum potassium.

PMID- 16994593
TI  - The effect of anterior pituitary extracts on acetone body excretion in the rat.

PMID- 16994595
TI  - Toxaemia and carbohydrate metabolism.

PMID- 16994596
TI  - The actions of insulin and adrenaline in young adrenalectomized rabbits.

PMID- 16994597
TI  - Gaseous interchanges through the visceral pleura of the cat.

PMID- 16994598
TI  - Repetitive stimulation by commutator and condenser.

PMID- 16994599
TI  - The curariform activities of strychnine metho-salts and curarine chloride.

PMID- 16994600
TI  - The renal elimination of phenol red.

PMID- 16994601
TI  - Temperature changes and winter sleep of bats.

PMID- 16994602
TI  - The glycogen content of the rat heart.

PMID- 16994603
TI  - Observations on the composition of alveolar air on everest, 1933.

PMID- 16994604
TI  - Experiments on variations in blood composition.

PMID- 16994605
TI  - An apparent change of ph on stretching a muscle.

PMID- 16994606
TI  - The output of the foetal heart in the goat.

PMID- 16994607
TI  - The relation between total and initial heat in single muscle twitches.

PMID- 16994608
TI  - Depressor substances in extracts of intestine.

PMID- 16994609
TI  - Further observations on the physiology and pharmacology of a sympathetic
      ganglion.

PMID- 16994610
TI  - The effect of ovarian hormone on the pituitary, thyroid, and adrenal glands of
      spayed female rats.

PMID- 16994611
TI  - The effects of sympathetic stimulation and of adrenaline on muscle glycogen.

PMID- 16994612
TI  - The measurement of red cell volume: V. The behaviour of cells from oxalated and
      from defibrinated blood in hypotonic plasma and saline.

PMID- 16994613
TI  - The hypercoagulability of the blood due to intramuscular injection of sodium
      citrate.

PMID- 16994614
TI  - Reaction of the smooth muscle of the gastro-intestinal tract of the skate to
      stimulation of autonomic nerves in isolated nerve-muscle preparations.

PMID- 16994615
TI  - The direct chemical estimation of carbamino compounds of CO(2) with haemoglobin.

PMID- 16994616
TI  - The chemical relationships and physiological importance of carbamino compounds of
      CO(2) with haemoglobin.

PMID- 16994617
TI  - Variation in the activity of the rabbit hypophysis during the reproductive cycle.

PMID- 16994618
TI  - Species variation in the gonadotropic activity of the hypophysis.

PMID- 16994619
TI  - The assay of progestin.

PMID- 16994620
TI  - Further experiments on the relation of the pituitary gland to the action of
      insulin and adrenaline.

PMID- 16994621
TI  - The effect of cortical stimulation on gastric movements in the monkey.

PMID- 16994622
TI  - Reflex interruptions of rhythmic discharge.

PMID- 16994623
TI  - Conditions of foetal respiration in the goat.

PMID- 16994624
TI  - The utilization of oxygen by the uterus in the rabbit.

PMID- 16994625
TI  - Haemoglobin function in the developing chick.

PMID- 16994626
TI  - The development of blood-pressure reflexes.

PMID- 16994628
TI  - The origin of the Wever and Bray phenomenon.

PMID- 16994627
TI  - The fate of carotene injected into the circulation of the rat.

PMID- 16994629
TI  - The effect of choline on the liver fat of rats in various states of nutrition.

PMID- 16994630
TI  - Choline and liver fat in phosphorus poisoning.

PMID- 16994631
TI  - A comparative study of the effects of adding different sugars to the perfusion
      fluid through frog's heart and the influence of insulin over it.

PMID- 16994632
TI  - The presence in the vagus of fibres transmitting impulses augmenting the
      frequency of respiration.

PMID- 16994633
TI  - Muscular work in dogs submitted to different conditions of cardiac and splanchnic
      innervations.

PMID- 16994634
TI  - The antagonistic cardiac nerves and heart rate.

PMID- 16994635
TI  - The inhibition of water diuresis by afferent nerve stimuli after complete
      denervation of the kidney.

PMID- 16994636
TI  - The measurement of red cell volume: VI. The different "fragility" of the red
      cells of various mammals.

PMID- 16994637
TI  - Excitation and inhibition in the retina and in the optic nerve.

PMID- 16994638
TI  - The effect of frequency of excitation on the thermal response of medullated
      nerve.

PMID- 16994639
TI  - The effect of frequency of excitation on the total electric response of
      medullated nerve.

PMID- 16994640
TI  - The "inhibitory" effect of high-frequency stimulation and the excitation state of
      nerve.

PMID- 16994641
TI  - A further analysis of the effects of high-frequency excitation of nerve.

PMID- 16994642
TI  - Electric excitation of the fin nerve of sepia.

PMID- 16994643
TI  - The action potentials in maia nerve before and after poisoning with veratrine and
      yohimbine hydrochlorides.

PMID- 16994644
TI  - The effects of acetyl-beta-methyl choline on the gastric acidity of monkeys.

PMID- 16994645
TI  - Afferent impulses in the carotid sinus nerve (nerve of hering) during asphyxia
      and anoxaemia.

PMID- 16994646
TI  - Intensity discrimination and its relation to the adaptation of the eye.

PMID- 16994647
TI  - The adrenaline content of the suprarenal glands in scurvy and in inanition.

PMID- 16994648
TI  - The sympathetic dilator fibres in the muscles of the cat and dog.

PMID- 16994649
TI  - Some factors influencing the heat production of muscle after stretching.

PMID- 16994650
TI  - The anti-ketogenic substance and phlorhizin diabetes.

PMID- 16994651
TI  - The role of the nerves in the action of acetylcholine on the embryonic heart.

PMID- 16994652
TI  - On the alleged occurrence of acetylcholine in the saliva.

PMID- 16994654
TI  - The excitation of medullated and non-medullated nerves by currents of short
      duration.

PMID- 16994653
TI  - The effect of fat on gastric motility.

PMID- 16994655
TI  - Mortality of adrenalectomized young rats, with improved technique of operation,
      and after a period of treatment with cortical hormone.

PMID- 16994656
TI  - On the effect of a non-electrolyte upon the size of the action potential of
      nerve.

PMID- 16994657
TI  - Quaternary ammonium salts and the action currents in nerve.

PMID- 16994658
TI  - Local adaptation to flicker and its relation to light adaptation.

PMID- 16994659
TI  - The effect of oestrin on the uterine reactivity and its relation to experimental
      abortion and parturition.

PMID- 16994661
TI  - The action of oestrin on the uterus of the hypophysectomized and of the pregnant
      rabbit.

PMID- 16994660
TI  - The synergism between oestrin and oxytocin.

PMID- 16994662
TI  - Resistance to inspiration-its effects on respiration in man.

PMID- 16994664
TI  - Nerve impulses from branchial pressure receptors in the dogfish.

PMID- 16994663
TI  - Factors affecting blood glycolysis in vitro and in vivo.

PMID- 16994665
TI  - Variation in the sensitivity of different species of monkeys to oestrin.

PMID- 16994666
TI  - "Pseudo-parturition" in the mouse, and the relation of the placenta to post
      partum oestrus.

PMID- 16994667
TI  - Properties of human seminal plasma.

PMID- 16994668
TI  - A modification of Krogh's micro-method of gas analysis.

PMID- 16994669
TI  - A method of directly recording changes in the calibre of the bronchi.

PMID- 16994670
TI  - The part played by the splanchnic innervation in the emptying time of the
      stomach.

PMID- 16994671
TI  - Slow impulses from the cutaneous nerves of the frog.

PMID- 16994672
TI  - The acetylcholine equivalent of nervous tissues.

PMID- 16994674
TI  - The effect of vitamin d on the calcium content of the dentine.

PMID- 16994673
TI  - The course of cardiac nerve fibres in the pulmonary plexuses.

PMID- 16994675
TI  - Some immediate physiological effects of reduced cooling powers on human subjects.

PMID- 16994676
TI  - The response of the uterus of hypophysectomized rabbits to extracts of the corpus
      luteum.

PMID- 16994677
TI  - The relation of the spleen to formation of glycogen in the liver. With a note on
      the rate of absorption of glucose and lactic acid.

PMID- 16994678
TI  - Intravenous injection of oxygen with the animal under ordinary and increased
      atmospheric pressure.

PMID- 16994679
TI  - The afferent fibres from the abdomen in the splanchnic nerves.

PMID- 16994680
TI  - Studies in exophthalmos. The effect of certain sympathomimetic substances on the
      eye of the cat and dog.

PMID- 16994681
TI  - Undulatory changes, of uterine origin, in the arterial blood-pressure.

PMID- 16994682
TI  - Adrenaline vaso-dilatation in voluntary muscle.

PMID- 16994683
TI  - Oxytocic properties of blood extracts and their physiological significance.

PMID- 16994684
TI  - Hypoglycaemic action of insulin-phosphotungstate and phosphotungstic acid
      administered by mouth.

PMID- 16994685
TI  - On the reflex regulation of the cerebral blood flow and the cerebral vaso-motor
      tone.

PMID- 16994686
TI  - Observations on binocular fusion and rivalry.

PMID- 16994687
TI  - The effect of haemorrhage of varying degree on blood and plasma volume, on blood
      sugar, and on arterial blood-pressure.

PMID- 16994688
TI  - Some immediate effects of reduced cooling powers upon the water balance and
      related effects in the human subject.

PMID- 16994689
TI  - The relation between metabolic processes and the ventricular electrogram.

PMID- 16994690
TI  - The effect of liver feeding in relation to oxygen want.

PMID- 16994691
TI  - The elimination of xylose, creatinine and urea by the perfused mammalian kidney.

PMID- 16994692
TI  - The pharmacological estimation of adenosine and histamine in blood.

PMID- 16994693
TI  - "Recurrent fibres" of the dorsal roots.

PMID- 16994694
TI  - The influence of calcium on intestinal absorption.

PMID- 16994695
TI  - Some observations on salivary secretion.

PMID- 16994696
TI  - The effect of pituitary (posterior lobe) extract upon the urinary flow in non
      anaesthetized dogs.

PMID- 16994697
TI  - The explanation of the increase in systemic flow caused by occluding the
      descending thoracic aorta.

PMID- 16994698
TI  - Further observations on the respiratory-accelerator fibres of the vagus.

PMID- 16994699
TI  - Intermittent conduction in the spinal cord.

PMID- 16994700
TI  - The occurrence of several kinds of haemoglobin in human blood.

PMID- 16994702
TI  - The action of the ovarian hormones on the uterine muscle measured in vivo and in
      vitro.

PMID- 16994701
TI  - Some physiological and physical aspects of the surface tension of urine.

PMID- 16994703
TI  - Separation of the pubic bones following the administration of oestrogens to male
      mice.

PMID- 16994704
TI  - The effect of food and of exhaustion on the pituitary, thyroid, adrenal and
      thymus glands of the rat.

PMID- 16994705
TI  - Effects of sodium citrate on the alkali reserve and coagulability of the blood.

PMID- 16994706
TI  - Changes in the coagulability of the blood produced by citric acid and some of its
      decomposition products.

PMID- 16994707
TI  - The action potential of the superior cervical ganglion.

PMID- 16994708
TI  - Facilitation and inhibition in the superior cervical ganglion.

PMID- 16994709
TI  - The carbohydrate metabolism of gut muscle.

PMID- 16994710
TI  - The mechanical activity of gut muscle under anaerobic conditions.

PMID- 16994711
TI  - Afferent fibres from the abdomen in the vagus nerves.

PMID- 16994712
TI  - Muscular force at different speeds of shortening.

PMID- 16994713
TI  - The chemical transmitter of the sympathetic nerve to the uterus.

PMID- 16994714
TI  - The response of the chemical receptors of the carotid sinus to the tension of
      CO(2) in the arterial blood in the cat.

PMID- 16994715
TI  - The estimation of oestrin and of male hormone in oily solution.

PMID- 16994716
TI  - The action of adrenaline on the respiratory quotient.

PMID- 16994717
TI  - An effect of choline upon the weights of young rats.

PMID- 16994718
TI  - The response of vagotomized animals to respiratory resistance.

PMID- 16994719
TI  - Choline and liver respiration.

PMID- 16994721
TI  - On the alleged occurrence of "krampfstoffe" in acetone extracts of mammalian
      brain.

PMID- 16994720
TI  - The blood flow through the skeletal muscle in relation to its contraction.

PMID- 16994722
TI  - Appearance of histamine in the venous blood during muscular contraction.

PMID- 16994723
TI  - Two types of retinae and their electrical responses to intermittent stimuli in
      light and dark adaptation.

PMID- 16994725
TI  - The fall in the blood lymphocytes of the dog under chloralose anaesthesia.

PMID- 16994724
TI  - The measurement of red-cell volume. Conductivity measurements.

PMID- 16994726
TI  - Vitamin B(1) deficiency in the rat's brain.

PMID- 16994727
TI  - Slow potential waves in the superior cervical ganglion.

PMID- 16994728
TI  - The fate of the antidiuretic principle of postpituitary extracts in vivo and in
      vitro.

PMID- 16994729
TI  - On the question of the utilization of amino acids and fat by the mammalian heart.

PMID- 16994730
TI  - The effect of antithyrotropic serum on the thyroid gland of guinea-pigs treated
      with thyrotropic hormone.

PMID- 16994731
TI  - Intensity discrimination and its relation to the adaptation of the eye.

PMID- 16994732
TI  - Further observations on the secretion by the submaxillary gland of the cat
      following sympathetic stimulation.

PMID- 16994733
TI  - The heat production of cat's nerve.

PMID- 16994734
TI  - The effect of salivary activity on the composition of bovine blood.

PMID- 16994735
TI  - Insulin and the thyroidectomized rabbit.

PMID- 16994736
TI  - The Sherrington phenomenon.

PMID- 16994737
TI  - Oxygen dissociation curves and osmotic pressures of haemoglobins of different
      species.

PMID- 16994738
TI  - Vaso-constriction following deep inspiration.

PMID- 16994739
TI  - The secretagogue and depressor substances in saliva and pancreatic juice.

PMID- 16994740
TI  - Electrical studies on the frog's labyrinth.

PMID- 16994741
TI  - Solvent water in the mammalian erythrocyte.

PMID- 16994742
TI  - A method for determination of carbon dioxide applicable to blood and tissues.

PMID- 16994743
TI  - The effect of potassium on the excitability and resting metabolism of frog's
      muscle.

PMID- 16994744
TI  - Uterine changes in experimental abortion and their relation to parturition.

PMID- 16994745
TI  - The influence of thyroid feeding on nembutal poisoning.

PMID- 16994746
TI  - Anterior pituitary extracts and liver fat.

PMID- 16994747
TI  - The effect of water intake upon human reactions to reduced cooling powers.

PMID- 16994748
TI  - The action of adrenaline on serum potassium.

PMID- 16994749
TI  - Some factors influencing the survival of rats after adrenalectomy and the
      suitability of the young rat for testing the potency of adrenal cortical
      extracts.

PMID- 16994750
TI  - The effect of pregnancy and pseudopregnancy upon the blood lipoids of rabbits.

PMID- 16994751
TI  - Potassium changes in the stimulated superior cervical ganglion.

PMID- 16994752
TI  - Respiration and the venae cavae-further x-ray cinematographic studies.

PMID- 16994753
TI  - Transmission through a lumbar sympathetic ganglion.

PMID- 16994754
TI  - The acetylcholine content of the cerebro-spinal fluid of dogs.

PMID- 16994755
TI  - The response of medullated nerve to alternating high-frequency stimulation.

PMID- 16994756
TI  - The action of potassium on the superior cervical ganglion of the cat.

PMID- 16994757
TI  - The liberation of acetylcholine by potassium.

PMID- 16994758
TI  - The effect of diets low in choline.

PMID- 16994759
TI  - Gonadotropic activity of the pituitaries of vitamin E deficient rats.

PMID- 16994760
TI  - The occurrence of ovulation and pseudo-pregnancy in the rabbit as a result of
      central nervous stimulation.

PMID- 16994761
TI  - The "lipotropic" effect of dietary protein.

PMID- 16994762
TI  - The effects of cholesterol and choline on liver fat.

PMID- 16994763
TI  - Release of acetylcholine at voluntary motor nerve endings.

PMID- 16994764
TI  - The constrictor response of the inferior vena cava to stimulation of the
      splanchnic nerve.

PMID- 16994765
TI  - Stream-lines in the abdominal vena cava.

PMID- 16994766
TI  - Chlorophyll and haemoglobin regeneration after haemorrhage.

PMID- 16994767
TI  - Observations on the nerves of supply to the bladder and urethra of the cat, with
      a study of their action potentials.

PMID- 16994768
TI  - Maintenance of pregnancy in the hypophysectomized rabbit with progestin.

PMID- 16994769
TI  - The response to drugs of gut muscle in asphyxia and in iodoacetic acid poisoning.

PMID- 16994770
TI  - Liberation of histamine by the heart muscle.

PMID- 16994771
TI  - The responses of normal and hypophysectomized rabbits to adrenaline.

PMID- 16994772
TI  - Certain effects of pulmonary gas embolism.

PMID- 16994773
TI  - The breakdown of a colour match with high intensities of adaptation.

PMID- 16994774
TI  - The duodenum and the automatic control of gastric acidity.

PMID- 16994775
TI  - The acclimatization of the human subject to atmospheres containing low
      concentrations of carbon monoxide.

PMID- 16994776
TI  - The oxygen consumption and carbohydrate metabolism of the retractor muscle of the
      foot of Mytilus edulis.

PMID- 16994778
TI  - Some observations on genesis of somatic movements in sheep embryos.

PMID- 16994777
TI  - Excitability of sensory fibres in Maia nerve.

PMID- 16994779
TI  - The chemical transmitter of motor impulses to the stomach.

PMID- 16994781
TI  - Formation of glycogen in the liver of anaesthetized cats with notes on specific
      action.

PMID- 16994780
TI  - Further studies upon the reactions of the abdominal vena cava.

PMID- 16994782
TI  - Insulin and the storage of liver glycogen in anaesthetized cats.

PMID- 16994783
TI  - The influence of salt saturation upon the urinary response to pituitary
      (posterior lobe) extract.

PMID- 16994784
TI  - The action and fate of injected posterior pituitary extracts in the decapitated
      cat.

PMID- 16994785
TI  - Electrical responses of Maia nerve to single and repeated stimuli.

PMID- 16994786
TI  - Action of adrenaline on the perfused liver.

PMID- 16994787
TI  - Some observations on the denervated spleen.

PMID- 16994788
TI  - Oxygen transport of the foetal and maternal blood during pregnancy.

PMID- 16994789
TI  - Neuro-muscular transmission in crabs.

PMID- 16994790
TI  - On the biological assay of the cortical hormone by the survival method, in
      adrenalectomized young rats, and on the influence of the salt content of the
      hormone extract.

PMID- 16994791
TI  - The renal elimination of phenol red in the dog.

PMID- 16994792
TI  - Sympathetic vaso-dilatation in the skin and the intestine of the dog.

PMID- 16994793
TI  - Respiration and functional activity.

PMID- 16994794
TI  - Effects of vitamin E deficiency on the thyroid gland of the rat.

PMID- 16994795
TI  - The inhibition of water diuresis by pituitary (posterior lobe) extract and its
      relation to the water load of the body.

PMID- 16994796
TI  - The mechanism of the rhythmic changes in the calibre of the bronchi during
      respiration.

PMID- 16994797
TI  - The limiting rate of assimilation of glucose introduced intravenously at constant
      speed in the resting dog.

PMID- 16994798
TI  - The normal leucocyte picture in a hot climate.

PMID- 16994799
TI  - The heart rate of the sympathectomized dog in rest and exercise.

PMID- 16994800
TI  - The role of duodenal regurgitation in the automatic regulation of the gastric
      acidity.

PMID- 16994801
TI  - Maternal transference of fluorine.

PMID- 16994802
TI  - Reactions of the normal mammalian muscle to acetylcholine and to eserine.

PMID- 16994803
TI  - The antagonism between curarine and acetylcholine.

PMID- 16994804
TI  - The actions of antidromic impulses on ganglion cells.

PMID- 16994805
TI  - The action oe progesterone on the uterus of the rabbit and its antagonism by
      oestrone.

PMID- 16994806
TI  - Carbamino compounds of CO(2) with human haemoglobin and their role in the
      transport of CO(2).

PMID- 16994807
TI  - The genesis of respiratory movements in the foetus of the sheep.

PMID- 16994808
TI  - Dietary deficiency, nerve lesions and the dental tissues.

PMID- 16994809
TI  - The double motor innervation of the adductor muscle in the claw of the crayfish.

PMID- 16994810
TI  - Mechanism of the peripheral vascular responses to changes in blood gas tension in
      man.

PMID- 16994811
TI  - The spread of activity in the cerebral cortex.

PMID- 16994812
TI  - Alkaline resistance and spreading velocity of foetal and adult types of mammalian
      haemoglobin.

PMID- 16994813
TI  - Hue discrimination and its relation to the adaptation of the eye.

PMID- 16994814
TI  - Hue discrimination in normal and abnormal colour vision.

PMID- 16994815
TI  - The effect of adrenaline on muscle glycogen in adrenalectomized,
      thyroidectomized, and hypophysectomized rats.

PMID- 16994816
TI  - Contralateral effects from tension receptors in skeletal muscle.

PMID- 16994817
TI  - On the specific vaso-dilating and plain muscle stimulating substances from
      accessory genital glands in man and certain animals (prostaglandin and
      vesiglandin).

PMID- 16994818
TI  - The technique of suprarenalectomy in the guinea-pig and the survival period and
      cause of death of guinea-pigs after bilateral suprarenalectomy.

PMID- 16994819
TI  - Multiple response to constant current in frog's medullated nerve.

PMID- 16994820
TI  - Dilatation of veins in response to tapping in man and in certain other mammals.

PMID- 16994821
TI  - The reactions of the abdominal vena cava.

PMID- 16994822
TI  - Stream-lines in the abdominal vena cava in the late stages of pregnancy.

PMID- 16994823
TI  - The acetyloholine metabolism of a sympathetic ganglion.

PMID- 16994824
TI  - Reflex slowing of respiration accompanying changes in the intrapulmonary
      pressure.

PMID- 16994825
TI  - Species variation in thyrotropic activity of the pituitary gland.

PMID- 16994826
TI  - Inhibition of ovulation in the rabbit by anti-gonadotropic serum.

PMID- 16994827
TI  - The effect of certain hormones on the activity of the uterine muscle of the
      guinea-pig.

PMID- 16994828
TI  - Experiments on the mechanism of strychnine "curarization".

PMID- 16994829
TI  - Sympathetic vaso-dilator fibres in the hare and the monkey compared with other
      species.

PMID- 16994830
TI  - The induction of pseudo-pregnancy in the rat by electrical stimulation through
      the head.

PMID- 16994831
TI  - Water metabolism in relation to the menstrual cycle.

PMID- 16994832
TI  - "Sensitization" by injury of the cutaneous nerve endings in the frog.

PMID- 16994833
TI  - The relation of the pituitary to liver glycogen production and utilization.

PMID- 16994834
TI  - Adrenaline and the blood lactic acid level in hypophysectomized rabbits.

PMID- 16994835
TI  - The study of the carotid sinus respiratory reflexes by means of chronic
      experiments.

PMID- 16994836
TI  - The electrical responses of dark-adapted frogs' eyes to monochromatic stimuli.

PMID- 16994837
TI  - Effects on the knee jerk of stimulation of the central end of the vagus and of
      various changes in the circulation and respiration.

PMID- 16994838
TI  - The action of adrenaline on the knee jerk.

PMID- 16994839
TI  - The changes in viscosity of an unstriated muscle (Mytilus edulis) during and
      after stimulation with alternating, interrupted and uninterrupted direct
      currents.

PMID- 16994840
TI  - Afferent impulses in the nerves supplying the urinary bladder.

PMID- 16994841
TI  - Observations on the renal circulation and secretion in the dog, with special
      reference to the effect of pituitary (posterior lobe) extract.

PMID- 16994842
TI  - The effect of electrotonus on the excitability of nerve.

PMID- 16994843
TI  - Pharmacological experiments on mammalian voluntary muscle, in relation to the
      theory of chemical transmission.

PMID- 16994845
TI  - The standardization of cortical extracts by the use of drakes.

PMID- 16994844
TI  - The total osmotic concentrations in serum and aqueous humour.

PMID- 16994846
TI  - The state in the blood and the excretion by the kidney of the antidiuretic
      principle of posterior pituitary extracts.

PMID- 16994847
TI  - The vaginal hydrogen-ion concentration in monkeys injected with oestrone.

PMID- 16994848
TI  - The transmission of impulses through the ciliary ganglion.

PMID- 16994849
TI  - On the effect of alternating currents on the cochlea.

PMID- 16994850
TI  - A further analysis of the action of alternating currents on the auditory
      apparatus.

PMID- 16994851
TI  - Impedance changes in muscle during contraction, and their possible relation to
      chemical processes.

PMID- 16994852
TI  - The effects upon the human electrocardiogram of the introduction of calcium and
      potassium into the blood.

PMID- 16994853
TI  - The effects of respiration upon the circulation through the liver, as studied by
      means of x-ray cinematography.

PMID- 16994854
TI  - The action of eserine and related compounds and of acetylcholine on the central
      nervous system.

PMID- 16994855
TI  - The influence of temperature on the isolated kidney of the dog.

PMID- 16994856
TI  - Action potentials of normal mammalian muscle. Effects of acetylcholine and
      eserine.

PMID- 16994857
TI  - The electrical responses of light-adapted frogs' eyes to monochromatic stimuli.

PMID- 16994858
TI  - The quantitative estimation of histamine in the blood.

PMID- 16994859
TI  - The Absorption of amino acids and their distribution in the body fluids.

PMID- 16994861
TI  - The chemical agent in the sympathetic control of retraction of the nictitating
      membrane of the cat.

PMID- 16994860
TI  - Vitamin B(1) and fatty livers.

PMID- 16994862
TI  - The insensitivity of the cervix uteri to oxytocin.

PMID- 16994863
TI  - The action of certain enzyme poisons on the frog's auricle.

PMID- 16994864
TI  - The absorption spectra of visual purple and of indicator yellow.

PMID- 16994865
TI  - Cholinesterase in voluntary frog's muscle.

PMID- 16994866
TI  - Cholinesterase in invertebrate muscles.

PMID- 16994867
TI  - Observations in man upon a blood pressure raising reflex arising from the
      voluntary muscles.

PMID- 16994868
TI  - Further observations on the action of acetylcholine, prostigmine and related
      substances on the knee jerk.

PMID- 16994869
TI  - AEtioporphyrin and haemoglobin regeneration after haemorrhage.

PMID- 16994870
TI  - Afferent fibres from the stomach and small intestine.

PMID- 16994871
TI  - A simple closed-circuit metabolism apparatus for small animals.

PMID- 16994872
TI  - The cholinesterase in sympathetic ganglia.

PMID- 16994874
TI  - The duration of the recovery period following strenuous muscular exercise,
      measured to a base line of steady, mild exercise.

PMID- 16994873
TI  - The actions of acetylcholine on denervated mammalian and frog's muscle.

PMID- 16994876
TI  - Ineffectiveness in birds of antisera for mammalian gonadotropic and thyrotropic
      substances.

PMID- 16994875
TI  - The inactivation of adrenaline.

PMID- 16994877
TI  - Measurement of the cardiac output in man.

PMID- 16994878
TI  - Ultramicroscopic particles in normal human blood.

PMID- 16994879
TI  - The excitation and response of smooth muscle.

PMID- 16994880
TI  - Rhythmic responses of smooth muscle.

PMID- 16994881
TI  - The secretory response of the posterior pituitary to the need for water
      conservation.

PMID- 16994882
TI  - Maintenance of ovarian and luteal function in the hypophysectomized rabbit by
      gonadotropic hormones.

PMID- 16994883
TI  - Maintenance of pregnancy and of the luteal function in the hypophysectomized
      rabbit.

PMID- 16994884
TI  - Distribution of chloride in frog's skeletal muscle immersed in saline solution.

PMID- 16994886
TI  - Evidence for electrical transmission in nerve: Part II.

PMID- 16994885
TI  - Evidence for electrical transmission in nerve: Part I.

PMID- 16994888
TI  - Vomiting produced, in the cat, by ligation of the mesenteric vein.

PMID- 16994887
TI  - Action potentials recorded from an unstriated muscle of simple structure.

PMID- 16994889
TI  - Liberation of histamine from the perfused lung by snake venoms.

PMID- 16994890
TI  - Liberation of histamine from the perfused lung by staphylococcal toxin.

PMID- 16994891
TI  - The liberation of histamine from the perfused lung by peptone.

PMID- 16994892
TI  - A study of cholesterol in the adrenal gland in different phases of reproduction
      in the female rat.

PMID- 16994893
TI  - Action of adrenaline on the serum potassium.

PMID- 16994894
TI  - The anti-strychnine action of acetylcholine, prostigmine and related substances,
      and of central vagus stimulation.

PMID- 16994895
TI  - The behaviour of crystallized secretin when digested with proteolytic enzymes.

PMID- 16994896
TI  - The aerobic metabolism of the isolated frog's heart poisoned by iodoacetic acid.

PMID- 16994897
TI  - A contribution to the study of ciliary movement.

PMID- 16994899
TI  - The reactivity during oestrus and pregnancy of the rat uterus to the oxytocic
      principle of the posterior pituitary gland.

PMID- 16994898
TI  - The source in blood of the histamine-like constituent.

PMID- 16994900
TI  - The female prostatic gland and its reaction to male sexual compounds.

PMID- 16994901
TI  - The action of anticoagulants.

PMID- 16994902
TI  - The role of appetite in the control of body weight.

PMID- 16994903
TI  - Ascending spinal pathways of the pupillo-dilator fibres.

PMID- 16994904
TI  - The radiographic examination of dental tissues in relation to their histological
      structure.

PMID- 16994906
TI  - Some characteristics of the action of urine upon amphibian melanophores.

PMID- 16994905
TI  - Excitation of the action potential of a molluscan unstriated muscle.

PMID- 16994907
TI  - Maintenance by oestrin of the luteal function in hypophysectomized rabbits.

PMID- 16994908
TI  - Oxidation of glucose as function of its supply.

PMID- 16994909
TI  - The behaviour of muscle following injection of water into the body.

PMID- 16994910
TI  - Reflexes from the bladder and large intestine.

PMID- 16994911
TI  - The rate of excretion of indian ink, injected into the lungs.

PMID- 16994912
TI  - The histamine-like activity of white blood cells.

PMID- 16994913
TI  - The isolation of histamine from the white cell layer of centrifuged rabbit blood.

PMID- 16994914
TI  - The discharge of impulses from ganglion cells.

PMID- 16994915
TI  - The energy liberation at constant diastolic fibre length in the tortoise heart
      with particular reference to the effect of the emptying pressure.

PMID- 16994916
TI  - A simple direct-coupled amplifier for action potentials.

PMID- 16994917
TI  - The sensation of yellow and anomalous trichromatism.

PMID- 16994918
TI  - The influence of the reaction of blood plasma on oxygen consumption in relation
      to the law of isodynamic equivalence.

PMID- 16994919
TI  - The relation between respiratory quotient and alveolar CO(2) tension.

PMID- 16994920
TI  - Synchronized reactions in the optic ganglion of dytiscus.

PMID- 16994921
TI  - The relation between plasma and cerebrospinal fluid calcium.

PMID- 16994922
TI  - The effects of tetra-ethylammonium iodide on the electrical response and the
      accommodation of nerve.

PMID- 16994923
TI  - Excitation and inhibition in the off-effect of the retina.

PMID- 16994924
TI  - The origin and limits of the specific dynamic action of intravenous glucose.

PMID- 16994925
TI  - The relation between the mechanical and electrical activity of a molluscan
      unstriated muscle.

PMID- 16994926
TI  - The cerebro-spinal fluid pressure of man in the erect posture.

PMID- 16994927
TI  - The pituitary gland and the control of urinary secretion.

PMID- 16994928
TI  - The local action of eserine on the central nervous system.

PMID- 16994929
TI  - The secretion of urine in man during experimental salt deficiency.

PMID- 16994930
TI  - Observations on the inactivation of adrenaline by blood and tissues in vitro.

PMID- 16994931
TI  - The mechanism of pitch change in the voice.

PMID- 16994932
TI  - The effect of anaerobic activity and rest on the efficiency of contraction in
      isolated frog muscle.

PMID- 16994933
TI  - The red cell count of macaques in relation to the menstrual cycle.

PMID- 16994934
TI  - The acclimatization of mice to atmospheres containing low concentrations of
      carbon monoxide.

PMID- 16994935
TI  - The "after-positivity" of stimulated nerve and its relation to the first phase of
      the recovery heat production.

PMID- 16994936
TI  - The transmission of impulses through the inferior mesenteric ganglia.

PMID- 16994937
TI  - Changes in creatine, phosphagen and adenylpyrophosphate in relation to the
      gaseous metabolism of the heart.

PMID- 16994938
TI  - Movements in midfoetal life in the sheep embryo.

PMID- 16994939
TI  - The "pancreotropic" action of anterior pituitary extracts.

PMID- 16994940
TI  - Effects of castration and of sexual hormones on the adrenals of male rats.

PMID- 16994941
TI  - The response of a denervated ganglion to acetylcholine.

PMID- 16994942
TI  - Lipoid substances of the ovary during ova production in rana pipiens.

PMID- 16994943
TI  - Factors affecting the sodium, potassium and total base content of the anterior
      retractor of the byssus of mytilus edulis.

PMID- 16994944
TI  - Exclusion of the liver in the rabbit.

PMID- 16994945
TI  - Binocular summation during dark adaptation.

PMID- 16994946
TI  - The action of curarine on the respiratory mechanism.

PMID- 16994947
TI  - The relation of the hypophysis to changes in sugar tolerance and insulin
      sensitivity induced by changes of diet.

PMID- 16994948
TI  - The action of tyramine and adrenaline on the denervated nictitating membrane.

PMID- 16994949
TI  - The carbonic anhydrase inhibitor in serum.

PMID- 16994950
TI  - Response of the cat's uterus to the hormones of the posterior pituitary lobe.

PMID- 16994951
TI  - The central depressor action of adrenaline and its inhibition by ergotoxine.

PMID- 16994952
TI  - The effect of hypophysectomy on the blood calcium and phosphorus of the rat.

PMID- 16994953
TI  - Heparin and the formation of white thrombi.

PMID- 16994954
TI  - A note on the effects of vitamin a deficiency in pregnant rats.

PMID- 16994955
TI  - Choline esterase in voluntary muscle.

PMID- 16994956
TI  - On the behaviour of glycogen after diets rich in protein and in carbohydrate.

PMID- 16994957
TI  - The effect of the interaction of ions, drugs and electrical stimulation as
      indicated by contraction of the anterior retractor of the byssus of mytilus
      edulis.

PMID- 16994958
TI  - Effect of drugs on the blood flow and activity of the uterus.

PMID- 16994959
TI  - The effect of anterior pituitary extracts on the liver fat of various animals.

PMID- 16994960
TI  - The effect of certain hormones on the activity of the uterine muscle of the
      mouse.

PMID- 16994961
TI  - The effect of the placenta on the body weight of the mouse.

PMID- 16994962
TI  - The influence of hydrogen-ion concentration on the surface tension of some
      colloidal solutions.

PMID- 16994963
TI  - Sensory fibres in the spinal accessory nerve.

PMID- 16994965
TI  - The action of creatine and creatinine on the circulatory system.

PMID- 16994964
TI  - Observations in man on a pulse-accelerating reflex from the voluntary muscles of
      the legs.

PMID- 16994966
TI  - The action of young's glycotropic factor of the anterior pituitary gland.

PMID- 16994968
TI  - The carbohydrate metabolism of the foetal dog under the influence of insulin.

PMID- 16994967
TI  - The effect of salt deficiency in man on the volume of the extracellular fluids,
      and on the composition of sweat, saliva, gastric juice and cerebrospinal fluid.

PMID- 16994969
TI  - Spectrophotometer investigation into the differences between foetal and maternal
      haemoglobin in man.

PMID- 16994970
TI  - Isotonic extension and shortening of the anterior retractor of the byssus of
      mytilus edulis.

PMID- 16994971
TI  - The effect of adaptation to electrical and chemical stimulation on the
      excitability of the anterior retractor of the byssus of mytilus edulis.

PMID- 16994972
TI  - Some conditions of foetal respiration in the cow.

PMID- 16994974
TI  - Antibodies organ-specific against the anterior body of the pituitary gland.

PMID- 16994973
TI  - The electrocardiogram of the guinea-pig.

PMID- 16994975
TI  - The interpretation of potential changes in the spinal cord.

PMID- 16994976
TI  - The action of narcotics on brain respiration.

PMID- 16994977
TI  - The buffering of muscle in rigor; protein, phosphate and carnosine.

PMID- 16994978
TI  - Blood histamine and cardiac activity.

PMID- 16994979
TI  - The osmotic pressure of the aqueous humour in the normal and glaucomatous eye.

PMID- 16994980
TI  - Experimental traumatic shock.

PMID- 16994981
TI  - Quantitative data on the inhibition of oestrus by testosterone, progesterone, and
      certain other compounds.

PMID- 16994982
TI  - Some factors influencing venous pressure in man.

PMID- 16994983
TI  - Antagonism between progesterone and the synthetic oestrogenic substance,
      triphenyl ethylene.

PMID- 16994984
TI  - The effect of adaptation on differential brightness discrimination.

PMID- 16994985
TI  - Action of hordenine compounds on the central nervous system.

PMID- 16994986
TI  - The respiration and metabolism of submaxillary gland tissue of the cat.

PMID- 16994987
TI  - The effect of large doses of insulin on the foetal sheep and goat.

PMID- 16994988
TI  - Coughing studied by means of x-ray cinematography.

PMID- 16994989
TI  - The role of leucocytes in fat absorption.

PMID- 16994990
TI  - On the mechanism of production, and the physiological significance of "apneusis".

PMID- 16994991
TI  - The thermal decomposition of visual purple.

PMID- 16994992
TI  - The after effects of a tetanus on mammalian muscle.

PMID- 16994993
TI  - The influence of anterior pituitary extracts, injected either with or without
      insulin, on the glycogen contained in the livers of fasting young rabbits.

PMID- 16994994
TI  - Segmental distribution of certain visceral afferent neurones of the pupillo
      dilator reflex in the cat.

PMID- 16994995
TI  - Carbonic anhydrase activity inside corpuscles. Enzyme-substrate accessibility
      factors.

PMID- 16994997
TI  - The effects of prolonged muscular exercise on the metabolism.

PMID- 16994996
TI  - Action of adrenaline, acetylcholine and other substances on nerve-free vessels
      (human placenta).

PMID- 16994998
TI  - The action of adrenaline in accelerating the removal of the blood sugar by the
      peripheral tissues.

PMID- 16994999
TI  - The carotid sinus and blood regeneration.

PMID- 16995000
TI  - The osmotic pressure of foetal and maternal sera in the sheep.

PMID- 16995001
TI  - The transmission of impulses by ganglionic direct fibres.

PMID- 16995002
TI  - The effect of asphyxia upon the heart rate of rabbits at different ages.

PMID- 16995003
TI  - On the mechanism of inhibition and excitation of crayfish muscle.

PMID- 16995004
TI  - Changes in muscle contraction curves produced by drugs of the eserine and
      curarine groups.

PMID- 16995005
TI  - Degenerative changes in the axis cylinders of the dental nerves, due to diets
      deficient in vitamin A and carotene.

PMID- 16995006
TI  - The action of eserine-like and curare-like substances on the responses of frog's
      nerve-muscle preparations to repetitive stimulation.

PMID- 16995007
TI  - The dependence of the activity of the "apneustic centre" on the carbon dioxide of
      the arterial blood.

PMID- 16995008
TI  - A micro blood volume method using a blue dye and photocell.

PMID- 16995009
TI  - Neuro-muscular conduction in the fowl.

PMID- 16995010
TI  - A plethysmographic method for measuring systolic blood pressure in the intact
      rat.

PMID- 16995011
TI  - The relation of contracture to the increment in the resting heat production of
      muscle under the influence of potassium.

PMID- 16995012
TI  - Synchronized impulse discharges from receptors in the deep tissues in response to
      a vibrating stimulus.

PMID- 16995013
TI  - On the absorption of ultra-violet radiation by human sweat.

PMID- 16995014
TI  - The phase angle of normal human skin.

PMID- 16995015
TI  - A study of the source of liver fat using deuterium as an indicator.

PMID- 16995016
TI  - On the accuracy of the thermostromuhr method for measuring blood flow.

PMID- 16995017
TI  - Experiments on the relation between the thyroid gland and lactation in the rat.

PMID- 16995018
TI  - Maximum growth rate of capon comb.

PMID- 16995019
TI  - Some effects of compounds of the androsterone-testosterone series on
      ovariectomized mice.

PMID- 16995020
TI  - The effect of the subarachnoid administration of histamine on the rate of
      absorption of isotonic saline solution in the dog.

PMID- 16995021
TI  - The effect of hypertonic solutions on gastric secretion and intraocular pressure.

PMID- 16995022
TI  - Properties of tonic contractions produced by electrical stimulation of the
      anterior retractor of the byssus of Mytilus edulis.

PMID- 16995023
TI  - Reactions of avian muscle to acetylcholine and eserine.

PMID- 16995024
TI  - The chloride content of blood serum and aqueous humour. Its relation to glaucoma
      and to the formation of intra-ocular fluid.

PMID- 16995025
TI  - Water balance and blood changes following posterior pituitary extract
      administration.

PMID- 16995026
TI  - Factors in sexual-skin oedema.

PMID- 16995027
TI  - Action of nicotine on the spinal cord.

PMID- 16995028
TI  - The absorption and excretion of iron following oral and intravenous
      administration.

PMID- 16995030
TI  - The rate of adaptation of cutaneous nerve endings in the frog.

PMID- 16995029
TI  - Liberation of acetylcholine by the perfused superior cervical ganglion.

PMID- 16995031
TI  - Functional impairment of the anterior pituitary gland produced by the synthetic
      oestrogenic substance 4:4' dihydroxy-alpha:beta-diethylstilbene.

PMID- 16995032
TI  - Nissl granules in "fatigued" nerve cells.

PMID- 16995033
TI  - The effect of high doses of androgenic substances on the weights of the testes'
      accessory reproductive organs and endocrine glands of young male guinea-pigs.

PMID- 16995034
TI  - The influence of the glycotropic (anti-insulin) factor of the anterior hypophysis
      on the insulin sensitivity of the hypophysectomized rabbit.

PMID- 16995035
TI  - Undernutrition and liver fat.

PMID- 16995036
TI  - The electrical activity of the cerebellum and its functional significance.

PMID- 16995037
TI  - The action of ephedrine.

PMID- 16995038
TI  - Liberation of histamine and formation of lysocithin-like substances by cobra
      venom.

PMID- 16995039
TI  - A new arrangement for the registration of diaphragm movements.

PMID- 16995040
TI  - The formation of lysocithin and of a muscle-stimulating substance by snake
      venoms.

PMID- 16995042
TI  - The time of functional closure of the foramen ovale in the lamb.

PMID- 16995041
TI  - Effects of cabbage extracts on carbohydrate metabolism.

PMID- 16995043
TI  - The suprarenals and the transmission of the activity of the sympathetic nerves of
      the cat.

PMID- 16995044
TI  - The blood-pressure raising secretion of the ischaemic kidney.

PMID- 16995045
TI  - Reflexogenic and central structures in oxygen poisoning.

PMID- 16995046
TI  - Early lesions of vitamin a deficiency.

PMID- 16995047
TI  - The effect of calcium and some other factors on the excitability of the anterior
      retractor of the byssus of Mytilus edulis.

PMID- 16995048
TI  - The utilization of various metabolites (blood fat and lactate, cardiac and lung
      glycogen) in the aglycaemic heart-lung preparation.

PMID- 16995049
TI  - The influence of diet upon ketonaemia in pregnant ewes.

PMID- 16995050
TI  - The young chick as test for the thyrotropic hormone.

PMID- 16995051
TI  - The air space of the hen's egg and its changes during the period of incubation.

PMID- 16995052
TI  - The experimental production of deafness in young animals by diet.

PMID- 16995053
TI  - The relation of transient orange to visual purple and indicator yellow.

PMID- 16995054
TI  - Concentration and sedimentation rates of blood from the splenic artery and vein.

PMID- 16995055
TI  - The "circular" musculature of the small intestine.

PMID- 16995056
TI  - On the mode of action of visual purple on the rod cell.

PMID- 16995057
TI  - Nervous discharges from the olfactory organs of fish.

PMID- 16995058
TI  - Studies on the chemical processes which occur in muscle before, during and after
      contraction.

PMID- 16995059
TI  - Experimental investigations of the reservoir blood of the cat spleen: with
      special reference to haemolysis and the sedimentation reaction.

PMID- 16995060
TI  - Reflex acceleration of respiration arising from excitation of the vagus or its
      terminations in the lungs.

PMID- 16995061
TI  - The oxygen and carbon dioxide content of the blood of normal and pregnant
      decerebrate cats.

PMID- 16995062
TI  - Some correlations between respiratory movements and blood gases in cat foetuses.

PMID- 16995063
TI  - The blood volume in lambs.

PMID- 16995064
TI  - A note on the manometric estimation of oxygen in small samples of blood.

PMID- 16995065
TI  - On the properties of secretin.

PMID- 16995066
TI  - The relation between conduction velocity and the electrical resistance outside a
      nerve fibre.

PMID- 16995067
TI  - The oxygen in the carotid blood at birth.

PMID- 16995068
TI  - Touch, pain and tickling: an electro-physiological investigation on cutaneous
      sensory nerves.

PMID- 16995069
TI  - Size of the spleen in relation to blood sedimentation rate.

PMID- 16995070
TI  - The creatinine, sugar, and urea equilibrium between plasma and lymph, aqueous
      humour, cerebro-spinal fluid, and gastric secretion after a hypertonic injection
      of these solutions.

PMID- 16995071
TI  - Liberation of histamine from the skeletal muscle by curare.

PMID- 16995072
TI  - The blood volume and kindred properties in pregnant sheep.

PMID- 16995073
TI  - The distribution of blood between the foetus and the placenta in sheep.

PMID- 16995074
TI  - Vagal reflexes appearing in asphyxia in rabbits at different ages.

PMID- 16995075
TI  - Blood flow during muscle contraction and the orbeli phenomenon in the dog.

PMID- 16995076
TI  - The inhibitory effect of acetylcholine on water diuresis in the dog, and its
      pituitary transmission.

PMID- 16995077
TI  - Choline esterase in voluntary muscle.

PMID- 16995078
TI  - Functional disorganization of the kidney in disease.

PMID- 16995079
TI  - The actions of quinine on skeletal muscle.

PMID- 16995080
TI  - The composition of particles seen in normal human blood under dark-ground
      illumination.

PMID- 16995081
TI  - Maintenance of pregnancy in the hypophysectomized rabbit by the administration of
      oestrin.

PMID- 16995082
TI  - Prolongation of red cell life by the spleen.

PMID- 16995083
TI  - A method for the continuous recording of systolic arterial pressure in man.

PMID- 16995085
TI  - Acetylcholine content of uteri before and after administration of oestrin to
      ovariectomized rabbits.

PMID- 16995084
TI  - The effect of peripheral vasomotor activity on systolic arterial pressure in the
      extremities of man.

PMID- 16995086
TI  - The direct determination of the oxygen consumption of the foetal sheep.

PMID- 16995087
TI  - Vasomotor reflexes in man following duodenal distension.

PMID- 16995088
TI  - A note on the suprarenal cortex and the transmission of the activity of the
      sympathetic nerves of the cat.

PMID- 16995089
TI  - The "anti-curare" action of a subthreshold catelectrotonus.

PMID- 16995091
TI  - The effects of stimulation of the cervical sympathetic nerve and the superior
      cervical sympathetic ganglion on the blood sugar.

PMID- 16995090
TI  - The central and reflex control of respiration in the frog.

PMID- 16995092
TI  - Synchronism of anuran lymph hearts and the integration of their spinal centres.

PMID- 16995093
TI  - The regulation of glyconeogenesis.

PMID- 16995094
TI  - The reflex response of the "apneustic" centre to stimulation of the chemo
      receptors of the carotid sinus.

PMID- 16995095
TI  - The effect of variations in carbon-dioxide tension on the rate of absorption of
      saline solution from the subarachnoid space.

PMID- 16995096
TI  - The effect of prolonged dosage with oestrogens on the adult brown leghorn cock.

PMID- 16995097
TI  - Histamine release in anaphylactic shock from various tissues of the guinea-pig.

PMID- 16995099
TI  - The capacity of pituitary preparations containing the thyrotrophic hormone to
      induce the formation of antisera.

PMID- 16995098
TI  - Surface tension and absorption spectrum of female urine over a menstrual cycle.

PMID- 16995100
TI  - The pharmacological actions of diethyl-stilboestrol and other oestrogenic and non
      oestrogenic substances.

PMID- 16995101
TI  - Blood-sugar variations in normal and in sympathectomized dogs.

PMID- 16995102
TI  - The role of the vagus in the cardio-accelerator action of atropine in
      sympathectomized dogs.

PMID- 16995103
TI  - The role of the vagus in the cardio-accelerator action of muscular exercise and
      emotion in sympathectomized dogs.

PMID- 16995104
TI  - The excitability states of inferior mesenteric ganglion cells following
      preganglionic activation.

PMID- 16995105
TI  - Determination of histamine in blood.

PMID- 16995107
TI  - The effect of pituitary (posterior lobe) extract on the body water of fish and
      reptiles.

PMID- 16995108
TI  - The effect of low-porphyrin diet on erythropoiesis and haemoglobin regeneration.

PMID- 16995106
TI  - The action of some amines related to adrenaline: methoxy-phenylisopropylamines.

PMID- 16995109
TI  - The influence of ingested radioactive materials upon the thyroid gland of rats.

PMID- 16995110
TI  - The effect of stretching and of stimulation on the weight, total base and sodium
      concentration of the anterior retractor of the byssus of mytilus edulis.

PMID- 16995111
TI  - The effect on the intestine of the substance liberated by adrenergic nerves in a
      rabbit's ear.

PMID- 16995112
TI  - The gastric secretions in experimental hypochloraemia.

PMID- 16995113
TI  - The relation between concentration of visual purple and retinal sensitivity to
      light during dark adaptation.

PMID- 16995114
TI  - The relation between force and speed in muscular contraction.

PMID- 16995115
TI  - The resistance of nerve in relation to interpolar length.

PMID- 16995116
TI  - Experimental oligocythaemia and splenomegaly.

PMID- 16995117
TI  - The influence of urea and of change in arterial pressure on the oxygen
      consumption of the isolated kidney of the dog.

PMID- 16995118
TI  - The indirect determination of the gas tensions in the mixed venous blood.

PMID- 16995119
TI  - The effect of forced breathing on the motor chronaxie.

PMID- 16995120
TI  - The origin and nature of ganglion after-potentials.

PMID- 16995121
TI  - Effect of clotting and of addition of histamine on its distribution in blood.

PMID- 16995122
TI  - The release of histamine by isolated smooth muscles.

PMID- 16995123
TI  - Some effects of stimulation of sympathetic nerves and injection of pressor drugs
      in adrenalectomized cats.

PMID- 16995124
TI  - Rotatory movements of the apex of the exposed mammalian heart.

PMID- 16995125
TI  - The effect of tetanus toxin on the choline esterase activity of the muscles of
      rats.

PMID- 16995126
TI  - The absorption of monosaccharides from the large intestine of the rat under
      urethane anaesthesia.

PMID- 16995127
TI  - Changes in elasticity of mammalian muscle undergoing rigor mortis.

PMID- 16995128
TI  - The distribution of sodium between the aqueous humour and blood plasma of cats.

PMID- 16995130
TI  - The effect of temperature upon dorsal root potentials in the frog.

PMID- 16995129
TI  - Nerve excitation by high-frequency alternating current.

PMID- 16995131
TI  - Respiratory accelerator action of the carotid sinus-cardiac depressor mechanism.

PMID- 16995132
TI  - Further observations upon the release of histamine by skeletal muscles.

PMID- 16995133
TI  - Use of the dietary anoestrous adults rat for the assay of the oestrus-inducing
      gonadotrophic substance.

PMID- 16995134
TI  - Acetylcholine synthesis in a sympathetic ganglion.

PMID- 16995135
TI  - The apparent augmentation of pituitary antidiuretic action by various retarding
      substances.

PMID- 16995136
TI  - Central action of anticholinesterases.

PMID- 16995137
TI  - The effect of the hydrogen-ion concentration on the stability of the antidiuretic
      and vasopressor activities of posterior pituitary extracts.

PMID- 16995138
TI  - The peripheral action of tetanus toxin.

PMID- 16995139
TI  - A comparative study of the effect of the interaction of ions, drugs and
      electrical stimulation as indicated by contraction of unstriated muscle.

PMID- 16995140
TI  - Properties of the substance liberated by adrenergic nerves in the rabbit's ear.

PMID- 16995141
TI  - The effect of monosaccharides on water absorption from the subarachnoid space.

PMID- 16995142
TI  - The effect of noxious agents on creatine, creatinine, chloride and water
      excretion.

PMID- 16995143
TI  - The effect of choline on the fatty liver of carbon tetrachloride poisoning.

PMID- 16995144
TI  - Diet and the insulin content of pancreas.

PMID- 16995145
TI  - Ketonaemia in pregnant ewes and its possible relation to pregnancy disease.

PMID- 16995146
TI  - The occurrence of ovulation in the rabbit as a result of stimulation of the
      central nervous system by drugs.

PMID- 16995147
TI  - The blood flow through muscle during sustained contraction.

PMID- 16995148
TI  - Gastric carbonic anhydrase.

PMID- 16995150
TI  - The quick component of nystagmus.

PMID- 16995151
TI  - The air stream in the lung of the fowl.

PMID- 16995149
TI  - Responses which nerve impulses evoke in mammalian striated muscles.

PMID- 16995152
TI  - Vaginal potentials in rabbits.

PMID- 16995153
TI  - Impulses in the pyramidal tract.

PMID- 16995154
TI  - The effect of anterior pituitary extracts on the insulin content of the pancreas.

PMID- 16995155
TI  - Afferent impulses from the teeth due to pressure and noxious stimulation.

PMID- 16995156
TI  - Afferent impulses from the teeth resulting from a vibratory stimulus.

PMID- 16995157
TI  - The diffusion of chloride and glucose into frog muscle.

PMID- 16995158
TI  - Fatty infiltration of the liver in pregnant ewes.

PMID- 16995159
TI  - Vascular changes affecting the transmission of nervous impulses.

PMID- 16995160
TI  - Amine oxidase and adrenaline.

PMID- 16995161
TI  - Vascular reactions of the cat after total sympathectomy.

PMID- 16995162
TI  - The sympathomimetic action of local anaesthetics.

PMID- 16995163
TI  - The inhibition of adrenaline oxidation by local anaesthetics.

PMID- 16995164
TI  - On the primary acidity of the gastric juice.

PMID- 16995165
TI  - The action in the perfused liver of acetylcholine, sympathomimetic substances and
      local anaesthetics.

PMID- 16995166
TI  - Effects of changes in dietary calcium on neuromuscular transmission.

PMID- 16995167
TI  - The oxygen supply of the foetal brain of the sheep and the effect of asphyxia on
      foetal respiratory movement.

PMID- 16995168
TI  - Oxygen in the blood of the umbilical vessels of the sheep.

PMID- 16995169
TI  - Effect of acetylcholine, prostigmine, potassium and fatigue on the crossed
      extensor reflex and on its reflex inhibition in the toad.

PMID- 16995170
TI  - The influence of diuretics on the osmotic work done and on the efficiency of the
      isolated kidney of the dog.

PMID- 16995171
TI  - The production of exophthalmos in the dog by acetylcholine.

PMID- 16995172
TI  - Effects of increased metabolism on ketosis of depancreatized dogs.

PMID- 16995173
TI  - Calcium and synaptic transmission in a sympathetic ganglion.

PMID- 16995175
TI  - A circulation model.

PMID- 16995174
TI  - On the disappearance from the blood of intravenously injected insulin.

PMID- 16995176
TI  - The formation of urine in the amphibian and mammalian kidney.

PMID- 16995177
TI  - The action of some amines related to adrenaline. Cyclohexylalkylamines.

PMID- 16995178
TI  - Electric interaction between two adjacent nerve fibres.

PMID- 16995179
TI  - The lipotropic action of methionine.

PMID- 16995180
TI  - The action of embryonic extracts on the sex organs.

PMID- 16995181
TI  - The absorption of monosaccharides from the distal small intestine of
      anaesthetized cats.

PMID- 16995182
TI  - Prolongation of pregnancy in the hypophysectomized rabbit by progesterone and
      oestrogens.

PMID- 16995183
TI  - Respiratory reflexes in the fowl.

PMID- 16995184
TI  - Glycogen and calcification.

PMID- 16995185
TI  - Capillary permeability and oedema in the perfused frog.

PMID- 16995186
TI  - The effect of temperature on the mechanical response and the viscosity and oxygen
      consumption of unstriated muscle.

PMID- 16995187
TI  - The inactivation of adrenaline by phenolases.

PMID- 16995188
TI  - Partial excitation and variable conduction in the squid giant axon.

PMID- 16995189
TI  - Correlation of local excitability with local physiological response in the giant
      axon of the squid (loligo).

PMID- 16995190
TI  - The composition of alveolar air.

PMID- 16995191
TI  - Effect of gravity on the blood pressure of the cat.

PMID- 16995192
TI  - The renal excretion of inulin and creatinine by the anaesthetized dog and the
      pump-lung-kidney preparation.

PMID- 16995193
TI  - The permeability of the blood-aqueous humour barrier to potassium, sodium, and
      chloride in the surviving eye.

PMID- 16995194
TI  - The effect of the interaction of ions, drugs and electrical stimulation as
      indicated by the contraction of mammalian unstriated muscle.

PMID- 16995195
TI  - Discharges from the sensory organs of the cat's vibrissae and the modification in
      their activity by ions.

PMID- 16995196
TI  - Transmission of light by the eye media.

PMID- 16995197
TI  - The effect of mono-iodoacetic acid on the absorption of water from glucose
      solutions in the subarachnoid space.

PMID- 16995198
TI  - The part played by the renal nerves in the production of water diuresis in the
      hypophysectomized and decerebrate dog.

PMID- 16995200
TI  - Determination of the metabolic rate of alcohol.

PMID- 16995199
TI  - The time course of the oxygen consumption of stimulated frog's muscle.

PMID- 16995201
TI  - Some factors affecting the metabolic rate of alcohol.

PMID- 16995202
TI  - The results of adrenalectomy in the pregnant albino rat.

PMID- 16995203
TI  - Effects of sympathomimetic amines on perfused blood vessels.

PMID- 16995204
TI  - The substance causing renal hypertension.

PMID- 16995205
TI  - Electrolyte content and action potential of the giant nerve fibres of loligo.

PMID- 16995206
TI  - The effect of renin on urine formation.

PMID- 16995207
TI  - The mechanisms of dilution diuresis in the isolated kidney and the anaesthetized
      dog.

PMID- 16995208
TI  - The inactivation of adrenaline in vivo in man.

PMID- 16995209
TI  - The effect of riboflavin, riboflavinphosphoric acid and the cortical hormone on
      the survival of adrenalectomized rats receiving normal and riboflavin-deficient
      diets.

PMID- 16995210
TI  - The "blue-green" region of the spectrum.

PMID- 16995212
TI  - The action of the antidiuretic principle of posterior pituitary extracts on the
      urine excretion of anaesthetized animals.

PMID- 16995211
TI  - The weight of the chromophore carrier in the visual purple molecule.

PMID- 16995213
TI  - The pituitary and the insulin content of pancreas.

PMID- 16995214
TI  - The action of some amines related to adrenaline: phenylallylamine,
      phenylbutenylamine, diphenylethylamine.

PMID- 16995215
TI  - The relation of heart rate to intracranial pressure.

PMID- 16995216
TI  - Observations on the osmotic pressure of the endolymph.

PMID- 16995217
TI  - The time course of evolution of oxidative recovery heat of frog's muscle.

PMID- 16995218
TI  - The anaerobic recovery heat production of frog's muscle at 0 degrees C.

PMID- 16995219
TI  - Hydrogen-ion concentration changes in frog's muscle following activity.

PMID- 16995220
TI  - Slow vaginal potentials.

PMID- 16995221
TI  - The absorption of water from the colon of the rat under urethane anaesthesia.

PMID- 16995223
TI  - The influence of diets low in magnesium upon the chemical composition of the
      incisor tooth of the rat.

PMID- 16995222
TI  - The action of adrenaline upon the uterus of the guinea-pig and its modification
      by eserine.

PMID- 16995224
TI  - A pump of small internal volume.

PMID- 16995225
TI  - The action of bee venom, cobra venom and lysolecithin on the adrenal medulla.

PMID- 16995226
TI  - Ions and adrenergic transmission in the rabbit's ear.

PMID- 16995227
TI  - Effects of vaso-dilator and vaso-constrictor substances on normal and denervated
      spleens.

PMID- 16995228
TI  - The relation between ureter, venous, and arterial pressures in the isolated
      kidney of the dog.

PMID- 16995229
TI  - Experimental cerebral concussion.

PMID- 16995230
TI  - The influence of the composition of the gastric content upon the effect of
      histamine.

PMID- 16995231
TI  - The influence of histamine on the absorption of sodium sulphate by the stomach.

PMID- 16995232
TI  - The influence of dietary calcium and phosphorus upon tooth formation.

PMID- 16995233
TI  - Surface and fragility differences between mature and immature red cells.

PMID- 16995234
TI  - The solubility of acetylene in blood: 1. Determination of acetylene dissolved in
      blood or other liquids.

PMID- 16995235
TI  - Bronchomotor responses to stimulation of the stellate ganglia and to injection of
      acetylcholine in isolated perfused guinea-pig lungs.

PMID- 16995236
TI  - Observations on the function of the round window.

PMID- 16995237
TI  - The influence of diets low in magnesium upon the histological appearance of the
      incisor tooth of the rat.

PMID- 16995238
TI  - The automatic collection of lung gases in cats.

PMID- 16995240
TI  - An improved electrically-heated operating board for small animals.

PMID- 16995239
TI  - The individual and integrated activity of the semicircular canals of the
      elasmobranch labyrinth.

PMID- 16995241
TI  - The influence of the sympathetic nervous system on capillary permeability.

PMID- 16995242
TI  - Vasoconstrictor nerves and oxygen consumption in the isolated perfused hindlimb
      muscles of the dog.

PMID- 16995243
TI  - The effect of adrenaline on nerve action potentials.

PMID- 16995244
TI  - The utilization of fat by the aglycaemic mammalian heart.

PMID- 16995245
TI  - The vaso-dilator action of potassium.

PMID- 16995246
TI  - The absorption of pentoses from the small intestine of the rat under urethane
      anaesthesia.

PMID- 16995247
TI  - The effect of adrenalectomy on the blood histamine of rabbits.

PMID- 16995248
TI  - The distribution of the pituitary antidiuretic hormone throughout the vertebrate
      series.

PMID- 16995249
TI  - A method of recording the respiration.

PMID- 16995250
TI  - The secretion of urine by newborn infants.

PMID- 16995252
TI  - Characteristics of the circulation of hypersensitive rabbits.

PMID- 16995251
TI  - Blood flow, arterial oxygen saturation, and oxygen consumption in the isolated
      perfused hindlimb of the dog.

PMID- 16995253
TI  - The action of acetylcholine, eserine and other substances on some motor responses
      of the central nervous system.

PMID- 16995254
TI  - A physiological study of the skin resistance response in man.

PMID- 16995255
TI  - Peripheral conduction rate in the sympathetic nervous system of man.

PMID- 16995256
TI  - Inulin and perabrodil clearance after alimentary haemorrhage in man.

PMID- 16995257
TI  - The movements of the unloaded uterus.

PMID- 16995259
TI  - The effect of the level of inorganic bases in blood on the catabolism of food
      protein.

PMID- 16995258
TI  - Amine oxidase in Sepia officinalis.

PMID- 16995260
TI  - Neuro-muscular transmission in the extrinsic muscles of the eye.

PMID- 16995261
TI  - Volume of interfibre spaces in frog muscle and the calculation of concentrations
      in the fibre water.

PMID- 16995262
TI  - The control of the external secretion of the pancreas in cats.

PMID- 16995263
TI  - The distribution of acetylcholine in the peripheral and the central nervous
      system.

PMID- 16995264
TI  - The effect of pregnancy on tissue lipides in the ewe.

PMID- 16995265
TI  - The identity and origin of the anticoagulant of anaphylactic shock in the dog.

PMID- 16995266
TI  - Skeletal changes affecting the nervous system produced in young dogs by diets
      deficient in vitamin a.

PMID- 16995267
TI  - The effect of ether on the rate of absorption of normal saline solution from the
      subarachnoid space.

PMID- 16995268
TI  - The influence of a tropical environment upon the basal metabolism, pulse rate and
      blood pressure in Europeans.

PMID- 16995269
TI  - Effect of light on red blood cells. The light sensitivity of blood from different
      vertebrate species.

PMID- 16995270
TI  - One pill, once daily: now an option for HIV patients.

PMID- 16995271
TI  - Antiretroviral rounds. Sperm washing for serodiscordant couples who want a child.

PMID- 16995272
TI  - Report from the XV International HIV Drug Resistance Workshop.

PMID- 16995273
TI  - Fertility nursing offers exciting opportunities.

PMID- 16995274
TI  - Natural orifice translumenal endoscopic surgery: "NOTES".

PMID- 16995275
TI  - In early RA, combination therapy with prednisone or infliximab leabs to earlier
      functional improvement and minor radiographic progression than other treatment
      strategies.

PMID- 16995276
TI  - Trauma: an annotated bibliography of the recent literature--2005.

PMID- 16995277
TI  - [Receptor sensitivity].

PMID- 16995278
TI  - [KCNQ channels].

PMID- 16995279
TI  - [MC4 receptor].

PMID- 16995280
TI  - Femtosecond stimulated Raman spectroscopy.

PMID- 16995281
TI  - Chemical analysis in nanoscale surfactant networks.

PMID- 16995282
TI  - Ineffective dose and lack of laser output testing in laser shoulder and neck
      studies.

PMID- 16995284
TI  - [Joint meeting of 28th annual meeting of the Japanese Society of Biological
      Psychiatry,  36th annual meeting of the Japanese Society of
      Neuropsychopharmacology, 49th annual meeting of the Japanese Society of
      Neurochemistry. Nagoya, Japan. September 14-26, 2006. Program and Abstracts].

PMID- 16995283
TI  - We have a new treatment, but you can't afford it.

PMID- 16995285
TI  - Epidemic alert and verification: summary report for 2005.

PMID- 16995286
TI  - Dengue haemorrhagic fever: early recognition, diagnosis and hospital management-
      an audiovisual guide for health-care workers responding to outbreaks.

PMID- 16995287
TI  - Physicians slow to adopt patient e-mail.

PMID- 16995288
TI  - Cardiac resynchronization therapy for heart failure.

PMID- 16995289
TI  - [ESPEN guidelines on enteral nutrition--summary].
AB  - Under the auspices of the European Society for Clinical Nutrition and Metabolism
      (ESPEN) clinical practice guidelines were systematically developed by 88 experts
      from 20 different countries between spring 2004 and winter 2005 in a predefined
      evidence and consensus based process. Evidence was gathered by a structured
      literature search, and the quality and strength of the evidence was graded
      according to published standards. On this basis recommendations were formulated
      which were then finalised in a consensus conference. The recommendations and
      their grades were summarized in table form. The German translation of these
      tables is now published for the following chapters: Intensive care, surgery
      including organ transplantation, non-surgical oncology, gastroenterology,
      pancreas, liver disease, adult renal failure, cardiology and pulmonology, wasting
      in HIV and chronic infectious diseases, geriatrics. The full text and the
      comments are available in ,,Clinical Nutrition" as well as on the internet under
      www.espen.org and www.dgem.de. The ESPEN guidelines enteral nutrition reflect the
      current medical knowledge in the field of enteral nutrition therapy and may help
      to decide when enteral nutrition is indicated and which therapeutic goals can be
      reached.

PMID- 16995291
TI  - [biliary lithiasis].

PMID- 16995290
TI  - [The influence of memory disorders on self-evaluation of subjective quality of
      life among schizophrenic patients].
AB  - INTRODUCTION: For the past few years, in the field of psychiatric disorders,
      measurements of subjective quality of life are integrated as an important
      criterion of judgment. The use of standardized questionnaires, based on the
      patients point of view has become widespread. However, in schizophrenic patients,
      cognitive impairement, and notably memory, is often advanced as a limit to the
      use of the self-reported questionnaires. METHODS: In this preliminary study, we
      investigated in 53 schizophrenic patients, the impact of memory impairment,
      specifically the episodic memory, on quality of life, taking into account
      confounding socio-demographic and clinical factors. The memory was assessed using
      the BEM 84. The patient's subjective quality of life was assessed by the self
      reported questionnaire S-QoL. RESULTS: No correlation was found between memory
      efficiency and quality of life level: patients with severe and non-severe
      impairment scored all the S-QoL domains similarly. DISCUSSION: However, the
      majority of schizophrenic patients could be considered as deficient on a wide
      assortment of neuropsychological evaluations, in particular in the attention and
      executive functions. The influence of the whole cognitive impairment of life must
      be confirmed.

PMID- 16995292
TI  - [Image of the week. Osteopetrosis].

PMID- 16995293
TI  - A new Swedish twin registry containing environmental and medical base line data
      from about 14,000 same-sexed pairs born 1926-58.
AB  - Since the beginning of the 1960's the Department of Environmental Hygiene of the
      Karolinska Institute and of the National Swedish Environment Protection Board has
      maintained a registry on about 10.000 same-sexed twin-pairs born 1886-1925. The
      registry has been used for studies of morbidity and mortality against the
      background of certain external risk factors, especially smoking. Supported by the
      Research Committee of the National Swedish Environment Protection Board, the
      establishment of a new twin registry covering younger age cohorts was initiated
      in 1970. The main purposes of this registry are to evaluate individuals'
      adaptation to changes in the environment and to study the effects of the
      environment on human health. Moreover, the registry is intended to be usable in
      obtaining specific target groups with a certain exposure. The main reason for the
      establishment of a twin registry instead of using a representative sample from
      the entire population is that a twin population offers some additional analytical
      possibilities. With twins composing the study group, it is possible to assess the
      role of the genetic factor for different variables. In addition, the twin
      approach provides opportunities of analyzing the subjects as matched pairs--the
      twin control method. This method involves the evaluation of the effect of one
      factor, to which one twin in the pair is exposed and the other not, while other
      variables are kept constant in a far-reaching way, e.g. sex, age, genetic
      composition, childhood, environment, etc. A twin registry can also be employed as
      a general epidemiological base line registry. For such purposes, the twin
      methodology is ignored, and the effects of some agent, for example having to do
      with environmental hygiene, are studied on all of the individuals, independently
      of their twin pair qualities. The registry is then in many regards comparable
      with a registry of non-twins. The first step in creating the Swedish twin
      registry was to compile information on names and addresses. By means of searches
      in birth records for the years 1926-1949 and birth notices for the years 1950
      1967, registration was made of ca 110 000 twin individuals, which constitute
      virtually all twins accounted for in official statistics. Of these, ca 13 800
      were stillbirths or infant deaths. Before the search for the twins' current
      addresses was begun, all pairs in which at least one individual was dead were
      eliminated. Such was the case in ca 10 250 pairs. The address search hence
      covered about 89 500 individuals and was carried out with the assistance of two
      location procedures. The first was applied to those born between 1926 and 1949
      and the second to those born between 1950 and 1967. The result was that in ca 96%
      of the pairs both members (37 590 pairs) or one member (4 853 pairs) could be
      found. It could be anticipated that of the latter pairs 1 450 would not be
      useable due to the death of one of the twins. The data collection has been
      carried out via a mail questionnaire which consists of the following main areas
      of inquiry: medication, annoyance experienced because of factors in the general
      and occupational environments, smoking and drinking habits, physical activity,
      food habits, psychosocial status, occupational and educational history,
      conditions of place of dwelling and certain background data. Before the
      questionnaire was sent out to the twin population, it was tested in a pilot
      investigation, which purported to study the effectiveness of the data collection
      procedure and to elucidate the validity of some of the individual questions. The
      pilot investigation showed an external nonresponse rate of 18%. Regarding the
      ability of the subjects to answer the questions, it was revealed that only a few
      of the question categories presented problems which gave rise to minor changes in
      the questionnaire. Comparison between the answers on the questionnaire and a
      parallel interview showed a high degree of agreement. Thus the questionnaire was
      considered satisfactory. The principal data collection was carried out during the
      period January - May 1973 and during the period December 1973 - February 1974. Of
      the 42 294 individuals included in the data collection, 3 339 could not be
      contacted because of death, illness etc. Responses have been received from 32 374
      individuals, which corresponds to 83% of the subjects who could be contacted.
      Regarded as a population of twin pairs, 3 262 pairs have not been utilizable for
      similar reasons. The total number of pairs in which both have answered the
      questionnaire is 13 811, corresponding to a little over 77%. There are three
      versions of the twin registry; a birth registry, an address registry and a
      questionnaire registry. The birth registry contains birth data from about 110,000
      twin individuals. The address registry contains in addition current information
      as to name and address as well as current and past census registration. The
      questionnaire registry, which comprises twins born 1926-1958, moreover contains
      information obtained on the basis of the mail questionnaire.

PMID- 16995294
TI  - [Importance of nanobiology and nanomedicine].
AB  - Focused on nanobiology and nanomedicine, this article elucidates its main
      research targets and contents, discusses the important of researches in this
      field, introduces the tasks and objectives of the corresponding researches in the
      national long- and mid-term science and technology development planning, and also
      describes the present research status in China.

PMID- 16995295
TI  - [Nanobiomaterials].
AB  - Nanobiomaterial is a multidisciplinary scientific field with roots in life
      science, material science and nanotechnology. The basic and application
      researches of nanobiomaterials have been the hot topic in the materials research
      for biomedicine and biotechnology, which have developed quickly in biomedical
      implant and intervention medicine, tissue engineering and regenerative medicine,
      and drug/gene delivery system. This review focuses on the potential of
      nanobiomaterials including biocompatible surface, tissue engineering and
      regenerative materials, new drug/gene delivery system and bioanalysis system,
      with an attempt to explore their possible applications in clinical practice.

PMID- 16995296
TI  - [Effect of gene transfer using nanoparticles as gene vector in different animal
      models].
AB  - OBJECTIVE: To evaluate the effect of antisense monocyte chemotactic protein-1 (A
      MCP-1) nanoparticles (NPs) as gene carrier on gene transfer in two kinds of
      animal models. METHODS: Poly (lactic acid-co-glycolic acid) (PLGA) was used to
      make the NPs loaded with A-MCP-1 through a double-emulsion/solvent evaporation
      technique. NPs size was assessed by dynamic laser defractometer. The particle
      morphology was observed by scanning electron microscopy. DNA content in the NPs
      was measured by dissolving known amounts of NPs in chloroform and extracting DNA
      with water. In vitro release was performed in tris-EDTA buffer at 37 degrees C
      using double-chamber diffusion cells. The receiver buffer was replaced daily. The
      A-MCP-1 NPs was transfected into the cultured smooth muscle cells. PCR was used
      to evaluate the transfection of A-MCP-1. Cationic lipid (Lipofectamine) was used
      to transfect A-MCP-1 as control. After 48 hours incubation, cells were digested
      and examined by polymerase chain reaction. Twenty New Zealand white rabbits under
      jugular vein to artery bypass grafting procedure were divided into four groups:
      the first group received grafts treated with A-MCP-1 NPs, the second group
      received grafts treated with cationic liposome (dioleoyl trimethyl ammonium
      propane)-A-MCP-1, the third group received grafts treated with plasmid DNA, and
      the fourth group received grafts without transfection as control. Fourteen days
      after surgery the grafts were harvested. The expression of A-MCP-1 and its effect
      on MCP-1 in vein grafts were detected by dot blotting. The morphology of the
      grafts was investigated. To establish abdominal aortic aneurysms rats model, rats
      were randomly divided into three groups: A-MCP-1 NPs injection group, shame NPs
      injection group and control groups (without injection). Two weeks after surgery,
      diameter of abdominal aorta was measured and aortic tissue was obtained for PCR
      analysis to evaluate the A-MCP-1 expression. Western blot were applied to detect
      the inhibitory effect to the expression of MCP-1 mRNA and CD68 protein by A-MCP-1
      NPs. RESULTS: NPs size ranged 198nm to 205nm with average around 201.4 nm. DNA
      content in the NPs was 4.14%. NPs showed steady release rate in vitro in Tris
      EDTA solution. It released faster in the first week then maintained a slowly
      sustained release up to 16 days. In cell culture A-MCP-1 gene successfully
      transfected into smooth muscle cells by NPs vector. In vein grafting animal
      model, A-MCP-1 expression was detected in the vascular walls of NPs and cationic
      lipid treated groups. The degree of vascular hyperplasia in the gene NPs treated
      group was significantly lower than that in control group. There was no
      significant difference in the inhibition of intimal hyperplasia between NPs and
      cationic lipid treated groups. Two weeks after transfection in abdominal aortic
      aneurysm rats models, the abdominal aortic diameter of A-MCP-1 NPs injection
      group was (1.79 +/- 0.12) mm, significantly smaller than that of control groups
      [shame NPs group was (2.58 +/- 0.21) mm, and saline group was (2.63 +/- 0.29) mm]
      (P < 0.01). The expressions of MCP-1 mRNA and CD68 protein in A-MCP-1 NPs
      injection group were 12.5 +/- 1.5 and 17.6 +/- 2.1, which were much lower than
      those in control group [in shame NPs group, which were 35.7 +/- 4.5, 42.3 +/- 5.7
      (P < 0.01), and saline group which is 32.4 +/- 3.9, 39.8 +/- 4.8 (P < 0.01)].
      Specific band of A-MCP-1 was detected only in the A-MCP-1 NPs injection group by
      PCR. CONCLUSION: A-MCP-1 gene NPs can be successfully used in rabbit vein
      grafting model and abdominal aortic aneurysm rats models, and may be potentially
      applied in clinical practice.

PMID- 16995297
TI  - [Construction of multifunctonal nano-delivery system crossing blood brain
      barrier].
AB  - OBJECTIVE: To construct multifunctonal nano-delivery system crossing the blood
      brain barrier (BBB). METHODS: The magnetic nanoparticles were preprared with O
      carboxylmethylated chitosan (O-CMC) and conjugated with a peptide sequence from
      the human immunodeficiency virus 1-tat protein and transferrin (Tf), and anti
      tumor drug methotrexate (MTX), and thus constructed a O-CMC magnetic
      nanoparticles carrier system conjugating with Tat and Tf (O-MNPs-Tat-Tf) that
      combines multiple functions including crossing BBB, magnetism, receptor-mediated
      dual targets and anti-tumor capabilities. The appearance, diameter, and magnetism
      of MTX-O-MNPs-Tat-Tf carrier system were characterized with transmission
      electronic microscopy, atomic force microscopy and vibrating samples
      magnetometer. The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with
      C6 glioma cells. The ability of O-MNPs-Tat-Tf crossing BBB was investigated in
      rats by single photon emission computed tomography. RESULTS: The mean particle
      diameter was 75 nm, along with good anti-tumor property. The multi-functioned
      carrier system successfully crossed the BBB in rat. CONCLUSION: The establishment
      of MTX-O-MNPs-Tat-Tf carrier model implies a promising future for its application
      in therapy of cerebral diseases.

PMID- 16995298
TI  - [Cellular uptake and cytotoxicity of modified chitosans as gene carriers].
AB  - OBJECTIVE: To evaluate the effects of arginine modified chitosan or hexadecylated
      modified chitosan as gene carriers on the cellular uptake by vascular smooth
      muscle cells and its in vitro cytotoxicity. METHODS Plasmid DNA was labeled with
      alpha-32P-dATP and complexed with the modified chitosans or unmodified chitosan
      to form nanoparticle complexes by complex coacervation method. Uptake of all
      kinds of chitosan/ DNA nanoparticle complexes (CNC) by A10 cells was measured by
      beta-liquid scintillation counting. The in vitro cytotoxicity of the CNC was
      evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide
      (MTT) assay. RESULTS: The diameters of the CNC ranged from 55.9-174.9 nm and the
      zeta potentials were from 10. 8 mV for the arginine modified chitosan/DNA
      nanoparticle complexes (ACNC) to 1.8 mV for the hexadecylated chitosan/DNA
      nanoparticle complexes (HCNC). The cellular uptake of the modified chitosan/ DNA
      nanoparticle complexes (MCNC) by A10 cells increased significantly when compared
      with the unmodified chitosan/DNA nanoparticle complexes (UCNC) (P < 0.05), with
      the HCNC at N/P ratio of 1:1 and the ACNC at ratio of 8:1 showing the highest
      cellular uptake (1.3 fold higher than UCNC, P < 0.05). MCNC were much less
      cytotoxic when compared with Lipofectamine 2000-DNA nanoparticles. CONCLUSION:
      DNA nanoparticle complexes prepared with either arginine or hexadecylated
      modified chitosan can improve the cellular uptake of the DNA, while the in vitro
      cytotoxicity of both of the modified chitosan is much less than that of
      Lipofectamine 2000.

PMID- 16995299
TI  - [Preparation and permeation studies of soybean lecithin-based vesicles].
AB  - OBJECTIVE: To investigate various methods for constructing soybean lecithin (SL)
      based vesicles and evaluate the permeation-enhancing effect of SL-based vesicles
      on the penetration of insulin through buccal mucosa. METHODS: The ultrasonic
      method, high speed shear method and high pressure homogenization method were
      respectively used to prepare the SL-based vesicles, and the particle size of the
      vesicles was measured with photon correlation spectrometry (PCS). The penetration
      rate of insulin through porcine buccal mucosa was investigated with the Valia
      Chien diffusion cells. RESULTS: The average particle sizes of 3 formulations of
      SL-based vesicles were 97.39, 85.60, and 100.60 nm when prepared by ultrasonic
      method, and were 58.7, 88.7, and 91.9 nm when prepared by high pressure
      homogenization method. Both vesicles presented good stability. However, the SL
      based vesicles prepared by high speed shear method had larger average diameters
      and were found to be unstable. Transmission electron microscopy showed that SL
      based vesicles had a spherical shape and the result accorded with PCS. The
      permeation flux of insulin of formulation 1 and control solution were 0.0024 and
      0.0008 IU x ml(-1) x min(-1), respectively. The accumulative amount of
      formulation 1 at 180 min was (0.436 +/- 0.010 ) IU x ml(-1), which was 1.46 times
      higher than the control solution. CONCLUSIONS: The SL-based vesicles obtained
      using high pressure homogenization method are characterized by small particle
      size, narrow distribution, good stability, and powerful permeation-enhancing
      effect, which enables them to be good carriers for the buccal delivery of
      insulin.

PMID- 16995300
TI  - [Preparation and evaluation of microbubble ultrasound contrast agent with N
      carboxymethyl chitosan].
AB  - OBJECTIVE: To prepare microbubble, made of N-carboxymethyl chitosan, as
      ultrasound contrast agent and evaluate its characteristics and acoustic effects
      in vivo. METHODS: Oil-Water-Oil multiple emulsion/solvent evaporation method was
      used to prepare the microbubble contrast agent. Both optical micrography and
      scanning electron micrography were performed to determine the bubble size and
      morphology. The acoustic effect of the N-carboxymethyl chitosan echo contrast
      agent was evaluated in vivo in rabbit. Liver echo images were recorded with
      ultrasound machine before and after intravenous bolus injecting 0.5 ml of the
      agent. RESULTS: The novel N-carboxymethyl chitosan echo contrast agent was
      formulated as lyophilized product, with a mean diameter of 2-3 microm and a shell
      thickness of 250-300 nm. Its size is relatively uniform. The imaging effect was
      remarkably enhanced with the ultrasonic contrast agent when applied in rabbit
      livers. CONCLUSION: It is feasible to prepare excellent microbubble ultrasound
      contrast agent with N-carboxymethyl chitosan as membrane components.

PMID- 16995301
TI  - [Characteristics of human adrenal microvascular endothelial cells in morphology,
      phenotypes, and function].
AB  - OBJECTIVE: To investigate the phenotypic and functional characteristics of human
      adrenal microvascular endothelial cells (AdrEC). METHODS: AdrEC were isolated and
      purified from a sample of human adrenal tissue by sub-cell clone method. The
      cells identified by flow cytometry for classical endothelial markers von
      Willebrand factor (vWF) and CD31, uptake of Dil-labeled acetylated low density
      lipoprotein (Dil-Ac-LDL), as well as phenotypes. The cell fenestrations were
      checked by scanning electron microscopy. The expressions of endogenous vascular
      endothelial growth factor (VEGF) mRNA and protein were detected by reverse
      transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. The
      glucocorticoid-induced cytotoxicities in different organs-derived microvascular
      endothelial cells were compared. RESULTS: Human AdrEC expressed those classical
      endothelial markers such as vWF, CD31, and uptake of Dil-Ac-LDL. The phenotypic
      analysis indicated that alpha-1 proteinase inhibitor, tumor necrosis factor
      receptor p55, and intercellular adhesion molecule-1 were expressed in human
      AdrEC. Scanning electron microscopy demonstrated that there were many microvilli
      and fenestrations on cellular surface. RT-PCR and immunocytochemistry showed that
      there was expression of endogenous VEGF in AdrEC. In response to glucocorticoid
      induced cytotoxicity, microvascular endothelial cells (MVEC) derived from human
      brain were highly susceptible, MVEC derived from human lung and human liver
      sinusoidal endothelial cells were sub-sensitive, while AdrEC were highly
      resistant. CONCLUSION: Human AdrEC are specially differentiated and have
      characteristics that are different from other organ-derived MVEC in phenotypes
      and functions.

PMID- 16995302
TI  - [Effects of expiratory triggering sensitivity on patient-ventilator expiratory
      synchrony and work of breathing in patients with chronic obstructive pulmonary
      disease during pressure support ventilation].
AB  - OBJECTIVE: To study the effects of expiratory triggering sensitivity (ETS) on
      patient-ventilator expiratory synchrony and work of breathing in chronic
      obstructive pulmonary disease (COPD) patients during pressure support ventilation
      (PSV). METHODS: A total of 31 COPD patients were ventilated in PSV mode, and
      measured by a pulmonary monitor. Meanwhile, the electromyogram of the diaphragm
      (EMG(diaph)) was obtained with electromyography. Five levels of ETS, 1%, 15%,
      25%, 35%, and 50% of peak inspiratory flow (PIF), were studied in random order.
      Each ETS level lasted 30 minutes and all the data were recorded simultaneously
      for 3 minutes at the end of each period. The effects of ETS on patient-ventilator
      expiratory synchrony were analyzed by measuring the phase angle of expiration
      between the EMG(diaph) and the flow wave curve, and the effects of ETS on work of
      breathing by calculating total work of breathing (Wtot), work of inspiration by
      patients (Wi, P) and expiratory work of breathing (Wex). RESULTS: Ten patients
      were excluded from the study. At the 25% PIF level of ETS, patient-ventilator
      expiratory synchrony was the best, theta = (8 +/- 3) degrees, 16 patients - 15
      degrees < or = theta < or = 15 degrees, and the amount of Wtot, Wi, p, Wex was
      the smallest among all the 5 levels of ETS, which was (1.86 +/- 0.53) J/L, (0.54
      +/- 0.13) J/L, and (0.16 +/- 0.08) J/L respectively. When the level of ETS
      decreased, the occurrence of delayed termination of inspiration and the amount of
      Wex increased. At the level of 1% PIF, 18 patients theta > 15 degrees, and Wex
      was (0.48 +/- 0.10) J/L; at this level of ETS, Wi, p also increased significantly
      to (0.65 +/- 0.16 ) J/L. But when the level of ETS increased, the occurrence of
      premature termination of inspiration and the amount of Wi, p increased: at 50%
      PIF level of ETS, theta < - 15 degrees and Wi, p was (1.33 +/- 0.14) J/L in 19
      patients. CONCLUSION: The proper adjustment of ETS during PSV improves patient
      ventilator synchrony and decreases work of breathing in COPD patients.

PMID- 16995303
TI  - [Gene transfer efficiencies and cell tropism of recombinant adeno-associated
      virus in the hippocampus of adult rat].
AB  - OBJECTIVE: To explore the gene transfer efficiencies and different cell tropism
      of recombinant adeno-associated virus 1 (rAAV1), rAAV 2, and rAAV 5 in the
      hippocampus of adult rats, and select more suitable gene vectors for central
      nervous system (CNS) gene therapy. METHODS: Eighteen SD male adult rat were
      divided into 3 groups randomly (n = 6), with every group being injected with the
      titre and volume matched rAAV1, rAAV2, and rAAV5 vectors. All these vectors
      contained enhanced green fluorescent protein (EGFP) sequences as a reporter gene.
      Animals were killed after 8 weeks. The coronal cryosections of brains were
      processed, and the EGFP gene expression was observed with fluorescence
      microscopy; the expression area and the number of EGFP positive cells were
      automatically measured using Image-Pro Plus 4.5 software. To identify their cell
      tropism in the CNS, the sections were counterstained with neuronal marker neuron
      specific nuclear protein (NeuN) and the astrocyte marker glial fibrillary acidic
      protein (GFAP) and were examined with a confocal laser scanning microscope.
      RESULTS: Eight weeks after adeno-associated virus gene transfer, the expression
      profile of EGFP demonstrated significant difference. Most of the pyramidal cell
      layers of CA1 to CA3 area and granular cell of dent gyrus were strongly
      transduced by rAAV1; whereas rAAV2 primarily transduced the cells of multiform
      layer in hilar region of the dentate gyrus; only a few pyramidal cells were
      transduced by rAAV5. Moreover, rAAV1 showed significantly wider distribution
      throughout the hippocampus, and the quantity of EGFP positive cells and the EGFP
      positive area were significantly more than those of rAAV2 and rAAV5 (P < 0.01).
      The counterstaining for NeuN and GFAP showed that rAAV1 was able to transduce
      both neurons and glia cells, whereas rAAV2 and rAAV5 transduced the neurons only.
      CONCLUSION: rAAV1 is an excellent transgene vector with higher efficiency and
      broader cell tropism in the CNS.

PMID- 16995304
TI  - [Thymus CT scan and thymoma associated antibodies in myasthenia gravis with
      thymoma].
AB  - OBJECTIVE: To investigate the clinical significance of the serum anti-titin, anti
      ryanodine receptor (RyR) antibody level and thymus CT scan in the diagnosis of
      myasthenia gravis with thymoma. METHODS: Totally 32 patients with myasthenia
      gravis who had received thymectomy were included in the study. Abnormalities were
      shown under CT scan of thymus in all these patients. The relationships were
      studied among the pathological diagnosis, CT findings, and serum level of thymoma
      associated antibodies: anti-titin and anti-RyR antibodies. RESULTS: The
      pathological diagnosis of thymoma was made in 21 patients and thymus hyperplasia
      in 11 patients after operation. The sensitivity of CT scan in the diagnosis of
      thymomas was 90.5%, the specificity of serum thymoma associated antibodies in the
      diagnosis of thymoma was 100%. CONCLUSION: The thymoma-associated antibodies test
      is helpful in the differential diagnosis of thymomas and thymus hyperplasia; when
      combined with CT scan, it may achieve high sensitivity in the diagnosis of the
      thymoma.

PMID- 16995305
TI  - [Role of endothelin-1 and its receptors on hypertrophy or proliferation of
      cultured cardial cells].
AB  - OBJECTIVE: To investigate the role of endothelin-1 and its receptors on
      hypertrophy or proliferation of cultured cardial cells. METHODS: Cardiomyocytes
      and cardiac fibroblasts were isolated by trypsin digestion method, DNA and
      protein synthesis were measured by 3H-dexyribonucleotidethymine (3H-TdR) and 3H
      Leucine (3H-Leu) incorporation, while protein content was measured by Bradford
      method. Atrial natriuretic peptide (ANP) mRNA expression of cardiomyocyte was
      measured by reverse transcripted-polymerase chain reaction. Selective endothelin
      (ET) receptor subtype antagonists BQ123 and BQ788 were used to block ET(A)
      receptors (ET(A)R) and ET(B)R respectively and to observe the effects of the two
      receptors during cardiac hypertrophy. RESULTS: ET-1 significantly increased the
      3H-TdR and 3H-Leu incorporation rate of cardiomyocytes and cardiac fibroblasts in
      a dose-dependent manner and increased protein content. Furthermore, ET-1 promoted
      the ANP mRNA expression of cardiomyocyte. ET(A)R antagonist remarkably blocked
      these effects, while ET(B)R antagonist had no obvious effect. CONCLUSIONS: ET-1
      can induce the hypertrophy for cardiomyocytes and the proliferation for cardiac
      fibroblasts. These effects are mediated by ET(A)R.

PMID- 16995306
TI  - [Comparison of chemical compositions between Dendrobium candidum and Dendrobium
      nobile].
AB  - OBJECTIVE: To compare the chemical compositions between Dendrobium candidum (D.
      candidum) and Dendrobium nobile (D. nobile). METHOD: Relative area and content of
      every chromatographic peak in the ammonic chloroform extracts of D. candidum were
      compared with those of D. nobile with high performance liquid chromatography-mass
      spectrometry. RESULTS: The relative area of alkaloids accounted for 2.34% and
      41.87% in D. candidum and D. nobile, respectively. The relative area of 25
      identical compositions took up 97.12% in the total area of D. candidum and 50.09%
      in that of D. nobile, and contents of 23 composition were higher in D. candidum
      than those in D. nobile. CONCLUSIONS: The quantity and contents of alkaloids are
      remarkably different between D. candidum and D. nobile. However, D. candidum has
      a higher quality than D. nobile in terms of the same chemical compositions.

PMID- 16995307
TI  - [Role of preoperative ultrasonography in evaluating early cervical metastasis in
      patients with differentiated thyroid carcinoma].
AB  - OBJECTIVE: To evaluate the role of preoperative ultrasonography in detecting
      early cervical lymph node metastasis in differentiated thyroid carcinoma.
      METHODS: Data were reviewed retrospectively from medical records between July
      2003 and July 2005, in which patients were divided into 2 groups: group A (study
      group): 51 (55 sides) patients of differentiated thyroid carcinoma patients with
      impalpable node but with ultrasonic positive nodal metastasis; group B (control
      group): 57 (64 sides) patients with preoperative palpable cervical lymph nodes.
      All patients had been undergone modified neck dissection. The preoperative
      ultrasonographic results and the preoperative pathologic finding had been
      compared in group A. RESULTS: In 51 patients (55 sides of preoperative positive
      ultrasonography 49 sides had been demonstrated cervical lymph nodes metastasis
      pathologically. The sensitivity of ultrasonography was 89.1%. Ultrasonography
      detected cervical lymph node believed to be uninvolved by physical examination in
      41.2% of patients. 65.5% of the cervical lymph metastasis was multilevel and the
      most frequent involvement site was middle neck and the involvement rate was 70.9%
      in ultrasonography. 75.5% of the cervical lymph metastasis was multilevel and the
      most frequent involvement site was level Ill (65.3%) in pathologic finding.
      CONCLUSIONS: Preoperative ultrasonograpy is a mainstay in detecting cervical
      lymph nodes metastasis in thyroid cancer patients. It can detect the early
      cervical lymph node metastasis and localize the position of the cervical
      metastasis. All the thyroid cancer patients should undergo preoperative
      ultrasonography and the extent of the neck dissection relies on the preoperative
      ultrasonic finding of the neck.

PMID- 16995308
TI  - [Surgical treatment on primary lesion of advanced pyriform sinus cancer].
AB  - OBJECTIVE: To evaluate the efficacy of surgical treatment and combined therapy of
      advanced pyriform sinus cancer. METHODS: Totally 153 patients with locally
      advanced pyriform sinus cancer who received surgical treatment in our department
      from January 1974 to December 1999 were divided into three groups: preoperative
      radiotherapy with 45.5 Gy followed by surgery (R + S group, n = 125), including
      32 laryngeal function sparing surgery; surgery alone (Sa group, n = 13); and
      surgery followed by postoperative radiotherapy with 56.3 Gy (S + R group, n =
      15). Twenty-one patients received piriformectomy, 10 piriformectomy plus partial
      laryngectomy, and 1 total hypopharyngectomy and pharyngoesophagectomy with
      laryngeal spared and colon reconstruction. Among 121 patients who did not receive
      laryngeal function sparing surgery, 13 received near total laryngectomy, 55 total
      laryngectomy, and 53 total laryngectomy plus total hypopharyngectomy and
      pharyngoesophagectomy with reconstruction. Eight-six patients received radical
      neck dissection, 14 modified neck dissection, and 6 lateral neck dissection.
      Survival rate and laryngeal function sparing rate were analyzed using Kaplan
      Meier and COX model respectively. RESULTS: The overall 5-year survival rates were
      46.51% in R + S group, 18.33% in Sa group, and 44.44% in S + R group. Laryngeal
      sparing rate were 13.61% (R + S group), 0 (Sa group), and 0 (S + R group),
      respectively. R + S group, S + R group and combined therapy group (R + S group
      plus S + R group) showed superiority over Sa group in teams of 5-year survival
      rate (P = 0.0364, P = 0.0462, P = 0.000). R + S group showed superiority over S +
      R group and Sa group in teams of laryngeal sparing rate. Therapy mode was the
      most important factor that contributed to 5-year survival rate and laryngeal
      sparing. No significant differences were found in complication rate among the
      groups. CONCLUSION: Preoperative radiotherapy conduces to preserve laryngeal
      function of patients with locally advanced pyriform sinus carcinoma.

PMID- 16995309
TI  - [Effects of atenolol and metoprolol on cardiomyocyte apoptosis and related gene
      expression after acute myocardial infarction in rats].
AB  - OBJECTIVE: To compare the beneficial effects of Atenolol and Metoprolol on
      cardiomyocyte apoptosis and related gene expressions after acute myocardial
      infarction (AMI) in rats. METHODS: AMI model was established with the ligation of
      anterior descending coronary artery in 251 randomly selected female SD rats.
      Twenty-four hours after operation, the 124 survivors were randomly assigned to
      AMI control group (MI group, n = 43), Atenolol group (group A, 10 mg x kg(-1) d(
      1), n = 39), and Metoprolol group (group B, 20 mg x kg(-1) x d(-1), n = 42). Sham
      operation group (group S, n = 27) was also established. Two subgroup (48 h
      subgroup and 4 weeks subgroup) was randomly divided in each group according to
      the time points. Drugs were given to each treatment group by gastric gavage 24 h
      after ligation. Cardiomyocyte apoptosis was detected with terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA
      ladder. Bcl-2, bax and caspase-3 genes were detected with immunohistochemistry
      and Western blot analysis. RESULTS: Compared with AMI control group, myocyte
      apoptosis rate (MAR) significantly decreased only in infarction area (P < 0.01)
      in group B. Bcl-2 expression was found to increase in myocytes of infarction,
      border and non-infarcted areas except for non-infarcted area of group A. Changes
      of the expressions of bax and caspase-3 was not significant. Four weeks after
      AMI, MAR was found to decrease significantly in scar, border and non-infarcted
      areas (P < 0.05, P < 0.01) in both group A and group B. No significant changes of
      bcl-2, bax and caspase-3 expressions was found except for a significant decrease
      of bax expression in non-infarcted area of group A. As indicated by Western blot,
      no significant change of the expressions of caspase-3, bcl-2 and bax were found
      in myocytes of group A and group B compared with AMI control group; however, bcl
      2/bax ratio significantly increased to the same level of sham-operated group (P <
      0.05). CONCLUSION: Both Atenolol and Metoprolol treatment can reduce
      cardiomyocyte apoptosis in infarction/scar, border and non-infarcted areas after
      AMI, mainly through the increase of bcl-2 expression and bcl-2/bax ratio.

PMID- 16995310
TI  - [Autologous versus allogeneic stem cell transplantation in adult patients with
      acute lymphoblastic leukemia].
AB  - OBJECTIVE: To explore the efficacy of autologous or allogeneic stem cell
      transplantation in adult patients with acute lymphoblastic leukemia (ALL) and
      investigate its relevant prognostic factors. METHODS: A total of 96 adult
      patients with ALL who had admitted to our hospital from November 1986 to June
      2004 were followed up till February 28, 2005. They were divided into autologous
      stem cell transplantation (Auto-SCT) group (n = 56) and allogeneic stem cell
      transplantation (Allo-SCT) group (n = 40). Auto-SCT group was further divided to
      treated subgroup, in which patients received graft-purified transplantation and
      (or) maintenance immunotherapy or chemotherapy after transplantation (n = 26),
      and non-treated subgroup (n = 30). Clinical characteristics of these groups were
      retrospectively analyzed. Survival date were analyzed by the Kaplan-Meier method
      and the prognostic factors were analyzed with the COX regression model. RESULTS:
      The 1-, 3-, and 5-year leukemia-free-survival (LFS) were not significantly
      different between the auto-SCT group and the allo-SCT group. The 3-and 5-year LFS
      of auto-SCT treated subgroup, auto-SCT non-treated subgroup and allo-SCT group
      were [(73.0 +/- 8.7)%, (69.2 +/- 9.0)%], [(42.2 +/- 10.1)%, (35.1 +/- 10.0)%],
      and [(50.9 +/- 8.2)%, (50.9 +/- 8.2)%], respectively, which showed statistical
      significance (P < 0.05). CONCLUSIONS: The long-term LFS is similar after auto-SCT
      and after allo-SCT. Purified graft and maintain immunotherapy or chemotherapy
      post-transplantation may decrease the relapse rate after auto-SCT and improve
      survival.

PMID- 16995311
TI  - [Recombinant expression of mutant human annexin V].
AB  - OBJECTIVE: To mutate human annexin V gene and transform it to Pichia Pastoris for
      mutant human annexin V expression, so as to be purified as active annexin V with
      endogenous metal chelating site. METHODS: The 5' and 3' end of native annexin V
      gene were mutated by specific primers. The mutant annexin V gene was inserted
      into pPIC9K and sequenced. The correct plasmid was linearized and transformed
      into Pichia Pastoris strain GS115 by electroporation. The transformants were
      selected from MD plates and cultured in BMGY medium and induced with methanol.
      The culture was centrifuged and the supernatant was analyzed by SDS-PAGE and
      silver staining. The binding activity of mutant human annexin V from culture
      supernatant was determined with phosphatidylserine exposed erythrocytes and
      fluorescein isothiocyanate-annexin V. RESULTS: The 5' end of native human annexin
      V gene was fused with GCAGGCGGCTGCGGCCAT coding sequence and 3' end 946-948 site
      TGT was mutated to AGC. Pichia Pastoris transformants secreted proteins of
      relative molecular mass 36 000 48 h after methanol induction. The concentration
      of this protein that inhibited 50% of the binding of fluorescein-annexin V was
      4nmol/L. CONCLUSION: Highly-active recombinant mutant human annexin V with
      endogenous metal-chelating sites can be expressed in Pichia Pastoris system.

PMID- 16995312
TI  - [Cultural characteristics of Armillaria mellea on solid media].
AB  - OBJECTIVE: To study the cultural characteristics of Armillaria mellea (A. mellea
      ) on solid media. METHODS: A. mellea was cultured on semi-solid agar medium in
      dark conditions. Effects of different media, carbon sources, nitrogen sources,
      and temperature on growth and morphology of A. mellea were observed. The contents
      of polysaccharide, mannitol, glucose, and reducing sugars in A. mellea during
      different stages of development were determined. RESULTS: The biomass and
      morphology of A. mellea were different in various media. Sugars were more
      effective carbon sources than the relevant sugar alcohols. Little molecular
      carbon sources such as alcohol and glycerol could be utilized by A. mellea, but
      starch only could be utilized slowly. Either organic or inorganic nitrogen
      sources could be uptaken and utilized effectively by A. mellea. No evidence was
      found that VitB1 affects the growth of A. mellea. The growth cycle on wort medium
      at 30 degrees C was shorter than that at 25 degrees C for 7 days. In logarithmic
      growth phase and stable phase, the polysaccharide contents of A. mellea were
      9.24% and 4.70% respectively, while the mannitol contents were 10.08% and 10.58%
      respectively; glucose and reducing sugar contents remained low level in the whole
      growth stage. CONCLUSIONS: Carbon sources have a more remarked effect on the
      growth of A. mellea than the nitrogen sources do. Optimal temperature for the
      growth of A. mellea ranges 20-30 degrees C. Mannitol accumulates more than other
      little molecular carbohydrates in A. mellea.

PMID- 16995313
TI  - [Expression of human micro-dystrophin gene after retrovirus infection in mdx mice
      bone marrow-derived mesenchymal stem cells].
AB  - OBJECTIVE: To construct the retroviral vector containing human micro-dystrophin
      gene and detect the expression of human micro-dystrophin in mdx mice bone marrow
      derived mesenchymal stem cells (MSCs) after retrovirus infection. METHODS:
      Retroviral vector for micro-dystrophin gene was constructed and transferred into
      the packing cell PA317 mediated by Lipofectamine 2000. The retroviral supernatant
      containing the target genes were subsequently used to infect mdx mice MSCs. Micro
      dystrophin expression was examined by methods of immunofluorescence staining and
      reverse transcriptase-polymerase chain reaction. RESULTS: Micro-dystrophin
      retroviral vector was successfully constructed and transferred into PA317 cells,
      and 48 h after infection with the recombinant retrovirus in mdx mice MSCs, 319 bp
      fragment could be detected by electrophoresis in the RT-PCR products. The red
      particles could be detected in some infected mdx mice MSCs with
      immunofluorescence staining. CONCLUSION mdx mice MSCs infected with retrovirus
      containing micro-dystrophin gene can express micro-dystrophin protein.

PMID- 16995314
TI  - [Effect of transplantation of wild-type bone marrow stem cells in mouse model of
      familial amyotrophic lateral sclerosis].
AB  - OBJECTIVE: To determine the effects of wild-type mouse bone marrow stem cells
      transplants on survival time and motor functions in the human mutant SOD1-G93A
      mouse model of familial amyotrophic lateral sclerosis (ALS). METHODS: Bone marrow
      stem cells derived from the wild-type male mice were delivered intravenously into
      25 ALS transgenic female mice (carrying the human SOD1 gene with Gly 93 Ala
      mutation) that had been pretreated with 5.5-6.5 Gy gamma-ray 5-7 days before. The
      onset time of limbs paralysis, lifespan and the graft versus host disease (GVHD)
      symptoms were observed in the treated group and statistically compared with
      control group of 15 media-injected ALS transgenic mice. The Sry gene (sex
      determine region on the Y chromosome) were detected by polymerase chain reaction
      technique in the blood sample of treated female ALS mice after 8 weeks of
      transplantation. A series of animal motor tests including rotating rods, rotated
      wheel and extension reflex were performed in both two groups at the same age of
      16-17 weeks to assess the mice survival motor functions. Results A few treated
      mice (7/25) had different clinical presentations of GVHD. The semi-quantity
      evaluation score of average GVHD among the treated ALS mice was not over 1-2. The
      detection of Sry gene on these treated female ALS group was positive. The average
      onsets of limb paralysis and survival time were prolonged for about 5 weeks. At
      the age of 16-17 weeks, the motor function in the treated group was significantly
      better than in the ALS control group (P < 0.01). CONCLUSIONS: Transplantation of
      wild-type mice bone marrow stem cells can prolong survival in the recipient mice
      and ameliorate motor dysfunction. Intravenous administration of normal bone
      marrow stem cells may have therapeutic values for ALS.

PMID- 16995315
TI  - [Prevalence and risk factors of retinopathy of prematurity].
AB  - OBJECTIVE: To investigate the prevalence and the risk factors of retinopathy of
      prematurity (ROP). METHODS: Totally 172 premature infants who were less than 37
      weeks postconceptional age, or more than 37 weeks but weighing < 2 500 g at
      birth, and born at PUMC hospital from May 1, 2003 to November 30, 2004, were
      enrolled in this study. Their fundus were routinely checked. Diagnosis and
      staging of ROP were performed according to the international guidelines. Another
      20 mature infants were selected as the control group. RESULTS: Twelve infants
      quitted the treatment or died. The remaining 160 infants completed the follow up.
      The prevalence of ROP in the premature group was 19.4%, while no ROP was found in
      the control group. The prevalence of ROP in subgroup with body weight < or = 2
      000 g (28.4%) was significantly higher than in subgroup with body weight > 2 000
      g (8.3%, chi2 = 10.217, P = 0.001) at birth. The prevalence of ROP in subgroup
      with postconceptional age < or = 32 weeks (42.5%) was significantly higher than
      in subgroup with postconceptional age > 32 weeks (11.7%, chi2 = 18.258, P =
      0.000). The postconceptional age (OR = 0.959, P = 0.036) and body weight (OR =
      0.999, P = 0.026) were the most important risk factors of ROP. Furthermore, blood
      transfusion ( OR = 0.076, P = 0.029) and Apgar score ( OR = 23.62, P = 0.012)
      were inversely correlated with ROP. Correlation was not found between ROP
      prevalence and oxygen inhalation mode, surface active substance, administration
      of dopamine and dexamethasone, and mother conditions. CONCLUSIONS: The prevalence
      of ROP is higher in premature infants than in mature infants. Shorter
      postconceptional age and lower body weight may result in higher ROP incidence.
      Routine screening of fundus in premature infants may be helpful for the early
      detection of ROP.

PMID- 16995316
TI  - [Ultrasonic bone mineral density of calcaneus in 1 816 healthy subjects in
      Guangxi autonomous region].
AB  - OBJECTIVE: To study the relationship between ultrasonic bone mineral density
      (BMD) of calcaneus and age, height, and body weight, and to establish the normal
      reference value for stiffness index (SI) of healthy subjects in Guangxi
      autonomous region and provide scientific foundation for the diagnosis and
      prevention of osteoporosis. METHODS: SI of calcaneus in 1 816 healthy adults aged
      11-90 years (775 men, 1 041 women) were measured with quantitative ultrasound.
      According to their ages, all the men and women were divided into 13 groups by 5
      year age group. RESULTS: SI reached peak values in 21-25 year group in men
      (range: 111.45 +/- 21.19) and in 16-20 year group in women (range: 101.26 +/-
      17.51). Then the SI value began to decline with aging. The SI featured by a
      typical dual-peak curve in women and the decrease rate of SI was faster in women
      than in men over 61 years. Multivariate linear regression analysis showed
      significantly negative correlation between SI and age (P < 0.001), positive
      correlation between SI and body weight (P < 0.05 for men; P < 0.01 for women),
      and positive correlation between SI and height in women (P < 0.01). CONCLUSION:
      SI correlates with age, height, and weight. The acquired SI value may provide a
      reference for the diagnosis of osteoporosis.

PMID- 16995317
TI  - [Effects of calcitonin on the pathology of spinal fusion in rabbit models].
AB  - OBJECTIVE: To observe the effect of calcitonin on the pathology of fusion in
      lumbar posterior/facet spinal fusion in rabbit model. METHODS: Thirty-two male
      New Zealand white rabbits were used to establish spinal fusion model. Sixteen
      rabbits received calcitonin at a dose of 1 IU x kg(-1) x d(-1) were classified as
      calcitonin group, and the remaining 16 rabbits as control group. Rabbits were
      killed 1, 2, 4, and 8 weeks after operations. Haematoxylin-eosin staining was
      applied to observe the pathological process of spinal fusion. Expression of bone
      morphogenetic protein-2 (BMP2) was detected by immunohistochemistry. RESULTS:
      Bone resorption and fibrovascular stroma formation were the main histological
      presentation 1 week after surgery. Two and 4 weeks after surgery, more cartilage
      formed with varying degrees of mineralization, while less trabeculae could be
      observed in the phase of active bone formation. No remarked margin was seen
      between cartilage and bone tissues. Eight weeks after surgery, trabeculae
      distributed widely. The pathological process of spinal fusion in calcitonin group
      was faster than in control group. Emery scores showed significant differences at
      different time points (F = 265.44, P < 0.001). Calcitonin and time had a
      positively synergistic effect on Emery scores, and calcitonin caused significant
      difference in terms of Emery scores since the second week (F = 22.43, P < 0.001).
      Expressions of BMP, were significantly different at different time points (F =
      1186.54, P < 0.001). Also, calcitonin and time had a synergistic effect on BMP2
      expression (F = 13.14, P < 0. 001). CONCLUSIONS: Endochondral ossification exists
      in the spinal fusion process and may be the main way of ossification. Calcitonin
      may stimulate the expression of BMP2 and thus accelerate the process of spinal
      fusion.

PMID- 16995318
TI  - [Application of nanobiological technology in medicine and its advances in China].
AB  - Nanobiological technology is an important research field in nanotechnology and
      has extensive applications in medicine. Although initiated lately, application of
      nanobiological technology in medicine is advancing in good pace in China, mainly
      involves in fields including nano-scale pharmaceutical carrier, nanoscale
      diagnostic technology, nanobiomaterials, and nano-scale traditional Chinese
      medicine.

PMID- 16995319
TI  - [Recent advances in liposomes and nanoparticles as drug carriers for drug
      delivery].
AB  - Liposomes and nanoparticles have been used as drug carriers to increase
      solubility, prolong drug duration in vivo, target drug delivery, reduce toxicity
      and combat multi-drug resistance. With major advances in the preparation
      techniques, preparation material, and surface modifiers in recent years,
      liposomes and nanoparticles delivery systems have achieved success in fields
      including cancer therapy, overcoming biological barriers, and biological drugs
      and vaccine carriage.

PMID- 16995320
TI  - [Advances in the investigation of biological effect and surface modification of
      dendrimers as drug (gene) delivery systems].
AB  - Dendrimers are highly branched macromolecules that have attractive nano-sized
      architectures. It seems that they can enter various cells easily because of their
      unique nanostructures and chemical properties, which make them to be one of
      important candidates of non-virus carriers for drug delivery or gene therapy.
      However, the understanding of cytotoxicity and related mechanisms of dendrimers
      are still limited. In recent years there has been rapid increases of researches
      regarding the biological effects of dendrimers, including the interactions of
      dendrimers to cells, transport mechanisms, intracellular distribution and
      biodistribution in vivo, as well as improvement of biocompatibility of dendrimers
      by surface engineering. In this paper, recent advances in the investigations of
      biological effect and surface modification for the dendrimers as drug or gene
      delivery systems were reviewed.

PMID- 16995321
TI  - [Protein microarray biosensor based on imaging ellipsometry and its biomedical
      applications].
AB  - A protein microarray biosensor based on imaging ellipsometry has been developed
      as a high-throughput and fast technique for protein analysis. As an automatic
      technique, it has advanced properties such as label-free, multi-protein
      simultaneous detection, static or kinetic analysis for protein interaction, and
      qualitative or quantitative analysis. It has been used for the biomedical
      applications including tumor markers detection, hepatitis B test, protein
      competitive adsorption and kinetic visualization for protein interactions. It
      have demonstrated promising potential for further applications in biomedicine.

PMID- 16995322
TI  - [Post-academic dental specialties 1. Their increase and future].
AB  - The rise in post-academic specialization by general dental practitioners in the
      Netherlands has turned out to be a powerful force in the research into several
      subfields, in the participation of dentists in post-academic dental education and
      in the expansion of the range of health care. Dentists have incorporated those
      developments in their professional practice and refer patients to colleagues with
      dental specialties, as necessary. The changes in the demand for dental care due
      to expanding treatment methods do, however, require adaptations of the regular
      academic dentistry curriculum. Several post-academic specialties should become
      part and parcel of the regular curriculum. This is all the more relevant in the
      light of the aspirations of Dutch administration to come to a new allocation of
      tasks within dental care. Without such adaptations, post-academic specialization
      and reshuffling of tasks would lead to the erosion of the dental profession. An
      advisory report called 'Innovations in Oral Care' will be submitted to the Dutch
      government in the near future. Aspirations to enrich the dental profession should
      take into account the various ways in which current and future dentists wish to
      to practice their profession.

PMID- 16995323
TI  - [Dentists on continuing dental education].
AB  - In support of its quality policy, the Dutch Dental Association (NMT) has
      undertaken a survey to examine dentists'views on continuing education,
      accreditation, and their postgraduate course attendance. In December 2004 a
      written questionnaire was sent to a sample of 710 dentists, of whom 504 (71%)
      responded. The data were analysed using SPSS. Most dentists (93%) attended one or
      more courses since January 2003. They tend to concentrate on a few subjects,
      mainly on clinical procedures. About half (45%) of the respondents are in favour
      of continuing education accreditation for dentists. Compared to opponents,
      supporters are more positive about continuing education in general and spend more
      time reading specialist literature. Furthermore, the greater part of dentists
      indicates that it is important to have some kind of quality mark for postgraduate
      courses.

PMID- 16995324
TI  - [Dentin demineralization in situ during frequent exposures to bananas or
      sucrose].
AB  - The aim of the study was to compare sucrose solution and bananas on
      demineralizing potential in situ, and to address the question if fluoride
      toothpaste is equally effective in preventing dentin demineralization at open,
      smooth surfaces and at plaque stagnation sites (grooves). Four volunteers wore an
      appliance containing bovine dentin specimens with narrow grooves and a smooth
      surface for two 1-week in situ periods, with 8 1-minute exposures daily: either
      by a rinse with 10% sucrose, or by consumption of a piece of banana. Twice daily,
      the appliance was dipped in toothpaste slurry of a fluoride-free toothpaste at
      one side and a fluoride toothpaste at the contralateral side. Demineralization
      was assessed by tranversal microradiography. No difference in dentin
      demineralization was found after frequent exposure to either sucrose solution or
      bananas. Fluoride toothpaste effectively protected dentin only at the smooth
      surfaces. In the grooves, fluoride affected the demineralization pattern; it
      drove lesions towards the bottom of the groove.

PMID- 16995325
TI  - [Popularity of aesthetic dental treatments. Results of a national study in the
      Netherlands].
AB  - There are indications of a growing public interest in aesthetic dental
      treatments. For want of reliable data, a group of 907 randomly selected Dutch
      individuals was questioned in order to give this apparent tendency a foundation
      in figures. The results of this study show that about 25% of the respondents
      received aesthetic dental treatment at some time, about 8% was treated during the
      past year, and almost 8% intended to undergo aesthetic dental treatment in the
      coming year. In this respect, tooth whitening was found to be the most popular
      treatment. The results of this study suggest that there is a positive attitude
      towards aesthetic dentistry and that women take a greater interest in it than
      men. Whether this interest will lead to a rise in the number of actual aesthetic
      dental treatments is still unclear.

PMID- 16995326
TI  - [A periodontal furcation problem in a mandibular premolar].
AB  - For several days a patient suffered from difficult to diagnose mandibular oral
      pain. The patient complained of pain and swelling for which no obvious
      explanation could be found. Eventually the cause became clear, as a second
      premolar with a mesial and distal root was found to have been affected by
      periodontal inflammation at the root furcation.

PMID- 16995327
TI  - Valdecoxib does not interfere with the CYP2D6 substrate metoprolol.
AB  - OBJECTIVE: We reported recently that celecoxib inhibits the metabolism of the
      cytochrome P450 (CYP)2D6 substrate metoprolol in volunteers. Valdecoxib, the
      active metabolite of parecoxib, has also been claimed to interfere with the
      metabolism of CYP2D6 substrates. However, little support for this contention is
      available despite the intensive use of parecoxib in the perioperative setting.
      Therefore, the objective of this study was to examine the effect of valdecoxib on
      the pharmacokinetics of the clinically relevant CYP2D6 substrate metoprolol.
      METHODS: An open, randomized, 3-period crossover study was performed in 15
      healthy male volunteers. Metoprolol (50 mg) was given in all 3 periods without,
      or following a 7-day pre-treatment with valdecoxib (20 mg, o.d.) or rofecoxib (25
      mg, o.d.), to achieve steady state conditions of COX-2 inhibitors in Periods 2
      and 3. In a small group of extensive metabolizers (EM/EM), short-term application
      of twice the dose was investigated. RESULTS: No effect of valdecoxib (20 mg/d) or
      rofecoxib (25 mg/d) were detected on the area under the plasma concentration-time
      curve of metoprolol (323 +/- 333 to 324 +/- 296 or 309 +/- 256 microg x h/l) or
      at a higher dose. No significant changes of pharmacokinetic or pharmacodynamic
      parameters of metoprolol were apparent. CONCLUSION: We conclude that, at
      therapeutic doses, valdecoxib and rofecoxib do not influence the CYP2D6 substrate
      metoprolol.

PMID- 16995328
TI  - Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their
      interaction with the immune system.
AB  - Echinacea is a widely used herbal remedy for the prevention and treatment of the
      common cold. Recently, many new insights concerning the molecular mode of action
      of the main lipophilic constituents, the alkamides, have renewed interest in this
      plant. In order to compare the bioavailability of alkamides from liquid and
      tablet preparations of E. purpurea (Echinaforce) in humans and to study the
      effects on ex vivo stimulated blood cells, a randomized, single-dose, crossover
      study with 10 (8 test, 2 placebo) volunteers has been performed. They received
      either 4 ml of the standardized E. purpurea (Echinaforce) tincture or 12 E.
      purpurea (Echinaforce) tablets or placebo. Both doses contained the same amount
      (0.07 mg) of the major alkamides, dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid
      isobutylamides. Liquid chromatography electrospray ionization ion-trap mass
      spectrometry was used to determine the content of alkamides in serum. It was
      found that the arithmetic mean C(max) of dodeca-2E,4E, 8Z,10E/Z-tetraenoic acid
      isobutylamides absorbed after oral application of the Echinaforce tincture
      appeared after 30 min (0.40 ng/ml serum). In comparison, the t(max) of tablets
      was 45 min with a C(max) of 0.12 ng/ml. An ex vivo stimulation of blood by LPS
      was carried out to measure the influence of E. purpurea on the innate and
      adaptive immune system. Both E. purpurea preparations led to the same effects on
      the immune system according to the concentration of pro-inflammatory cytokines
      TNF-alpha and IL-8. 23 hours after oral application a significant down-regulation
      of TNF-alpha and IL-8 in LPS pre-stimulated whole blood was found. However, no
      significant changes in the concentration of IL-6 were observed. Although a
      quarter of the dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides was absorbed
      from the tablets, the study shows that the formulations trigger the same effects
      on the measured immune parameters.

PMID- 16995329
TI  - Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community
      pharmacy-based cohort study.
AB  - INTRODUCTION: Mucoactive substances such as ambroxol, available in several
      countries as over-the-counter (OTC) medicines, are used for the treatment of
      acute and chronic bronchitis. OBJECTIVE: This study was designed to evaluate the
      "real life" behavior of consumers with non-prescription access to an ambroxol
      cough syrup with special focus on tolerability and the pattern of product usage.
      METHODS: Customers who bought the ambroxol syrup were recruited in 300 community
      pharmacies in Germany. Baseline data were collected from the participants in the
      pharmacy. Completing a self-administered questionnaire, participants provided
      information on tolerability, self-perceived effectiveness and usage pattern.
      RESULTS: 2,707 participants were recruited in 266 pharmacies. 2,664
      questionnaires were evaluable. At baseline, the respondents reported a complex
      pattern of symptoms. Productive cough, congested airways, dry cough, cough
      irritation in the throat and soreness in the throat were the most common ones. 67
      patients (2.5%) reported a total of 81 adverse events (AE) which were usually
      mild in nature and mostly affecting the gastrointestinal tract (n = 53) followed
      by skin and subcutaneous tissue disorders (n = 9). No serious or unknown AE were
      reported. In general, 97% of the participants assessed the safety as "very good"
      (51%) or "good" (46%). Overall, the respondents complied with the indications for
      use and the recommended dosages, with only 0.7% of the participants using the
      maximum daily dose. 92% of the patients assessed the self-perceived effectiveness
      as "very good" (29%) or "good" (63%) and 89% were willing to purchase this
      ambroxol cough syrup again. CONCLUSIONS: This study confirms that ambroxol is
      used according to the advice given in the patients' leaflet and supports the
      already established safety and efficacy of this product in acute bronchitis. It
      also demonstrates that the use of an OTC cough medication can be successfully
      monitored in a pharmacy-based cohort study.

PMID- 16995331
TI  - Dosage adjustment of quinolone antibiotics and angiotensin-converting enzyme
      inhibitors in patients with renal dysfunction.
AB  - The aim of this study was to verify an approach for calculating pharmacokinetic
      parameters suitable for adjusting dosage regimens in patients with renal
      dysfunction. We carried out a retrospective analysis of the pharmacokinetic
      profiles of 12 new quinolone antibiotics and 11 angiotensin-converting enzyme
      inhibitors (ACEIs) in patients with normal and impaired renal function to obtain
      the renal excretion ratio (R(renal)) of each drug. We demonstrated that the
      pharmacokinetics of each drug in a patient with renal dysfunction can be
      adequately estimated using the R(renaI) value of each drug together with the
      creatinine clearance as an index of the individual's renal function. Using the
      R(renaI) value obtained, we could successfully simulate pharmacokinetic profiles
      of the drugs in publications other than that used to obtain the R(renal) values.
      On the other hand, age-related changes in the pharmacokinetics of new quinolone
      antibiotics are not always adequately predicted using the R(renal) value compared
      to using creatinine clearance alone as an index, and the reasons for this are not
      fully understood. These results demonstrate that dosage regimens of quinolone
      antibiotics and ACEIs in patients with renal dysfunction can be adequately
      optimized using the R(renal) value for each drug using the present approach.

PMID- 16995330
TI  - Increase in renal vascular resistance after intake of cyclosporin A and
      tacrolimus and reversal by nitroglycerin spray: a study in patients with stable
      renal allograft function.
AB  - PURPOSE: Acute effects of drug administration on renal arterial resistance index
      (RI) are still discussed controversially. In our study we investigated the
      immediate effects of cyclosporin A (CyA) and tacrolimus (FK-506) on renal
      arterial resistance indices in patients with stable graft function after renal
      transplantation. Additionally we studied the effects of nitroglycerin spray on
      resistance indices. METHODS: RI was measured by color Doppler sonography at
      baseline, at 1 and 2 hours after intake of medication and 30 minutes after
      administration of nitroglycerin spray which followed the 2-hour measurement. 34
      renal transplant recipients were examined. 16 patients received CyA, 18 patients
      received FK-506. Whole blood levels of calcineurin inhibitors were taken at each
      time point. Arterial blood pressure and heart rate were measured to assess
      possible systemic hemodynamic effects. RESULTS: Mean RI values increased
      significantly in both groups 1 hour after calcineurin inhibitor intake and
      remained still significantly elevated after 2 hours. There was no significant
      increase of mean arterial blood pressure nor was there any correlation between
      whole blood levels of calcineurin inhibitors and mean RI. 30 minutes after
      administration of nitroglycerin spray, mean RI values decreased significantly to
      a level even below baseline. Mean arterial blood pressure also decreased after
      administration of nitroglycerin. CONCLUSION: Renal RI values are markedly
      influenced by a recent intake of calcineurin inhibitors and vasoactive substances
      such as nitrates. This demonstrates the necessity of keeping standardized
      conditions when using RI as a tool in followup investigations after renal
      transplantation.

PMID- 16995332
TI  - Differences between prescribed daily doses and defined daily doses of
      antiepileptics--therapeutic drug monitoring as a marker of the quality of the
      treatment.
AB  - OBJECTIVE: Prescribed daily doses (PDDs) of antiepileptics (N03A ATC group) were
      recorded for drugs used in monotherapy or in combination therapy in the
      University Hospital in Ostrava, Czechia. Plasma levels were used as an indicator
      of the quality of treatment. METHOD: Request and reply forms for therapeutic drug
      monitoring (TDM) were used as a source of PDDs and plasma levels. The study
      included 1,144 in-patients examined in the period 1993 - 2004. The differences in
      PDD were tested by Mann-Whitney-U-test. ATC/DDD index 2005 was used. Doses given
      in mono- and polytherapy were compared. RESULTS: Median PDDs in samples within
      the therapeutic range (in mg) in mono-/polytherapy were as follows (DDDs in
      parenthesis): carbamazepine 600/800 (1,000), clonazepam 2.0/2.0 (8), phenytoin
      300/300 (300), ethosuximide -/1000 (1,250), lamotrigine 250/200 (300),
      phenobarbital -/200 (100), primidone 500/625 (1,250), topiramate -/300 (300),
      valproic acid 750/1,000 (1,500). Median PDDs in polytherapy with antiepileptics
      not analyzed for TDM were: gabapentin 900 (1,800), levetiracetam 1,500 (1,500),
      vigabatrin 1,500 (2,000). CONCLUSIONS: PDDs in monotherapy were similar or
      slightly lower than in combination therapy with an exception for lamotrigine, NS.
      The differences were significant in carbamazepine, p < 0.0001, and valproic acid,
      p < 0.001. Patients with plasma levels within the therapeutic range were usually
      treated with similar or slightly higher doses than the remainder. In polytherapy
      the PDDs were similar to DDDs in carbamazepine, ethosuximide, phenytoin, and
      topiramate in samples within the therapeutic range when difference +/- 20 per
      cent was considered as acceptable PDD of levetiracetam was also similar to actual
      DDD. In general plasma levels tended to be below the therapeutic range. The
      differences between PDD and DDD of antiepileptics have to be taken into account
      especially when utilization of different drugs is compared.

PMID- 16995333
TI  - Ethanol does not significantly affect the bioavailability of almotriptan: an
      open, randomized, crossover, single-dose, phase I clinical trial in healthy
      volunteers.
AB  - OBJECTIVE: A number of clinical reports have revealed a link between the use of
      alcohol and the onset or exacerbation of migraine headaches. This open,
      randomized, crossover, single-dose, phase I clinical trial evaluated the possible
      pharmacokinetic interactions between a single oral dose of almotriptan 12.5 mg, a
      5-HT(1B/1D receptor agonist for the acute treatment of migraine, and ethanol in
      16 healthy male volunteers. Tolerability and safety of this combined treatment
      were also assessed. METHODS: Subjects received a crossed oral dose of almotriptan
      (12.5 mg) with and without concomitant alcohol intake (target plasma
      concentration 0.8 g/kg) in two different treatment periods. Almotriptan was
      administered alone, while ethanol was diluted with orange juice, which was also
      given to the control group. There was a washout period of 7 days between
      treatments. Plasma levels of almotriptan were analyzed using a sensitive and
      specific liquid chromatographic-tandem mass spectrometry method. RESULTS: The 90%
      non-parametric confidence interval for the median t(max) of almotriptan plus
      ethanol compared to almotriptan alone (0.61/2.72) was outside the acceptable
      range (0.70 - 1.30), demonstrating that concomitant ethanol administration
      slightly increases the variability of absorption of almotriptan 12.5 mg. In
      contrast, the main bioavailability criteria parameters, C(max) and AUC, which
      show the rate and extent of systemic absorption, were not affected by alcohol
      ingestion. Therefore, it is unlikely that concomitant ethanol intake would
      produce clinically relevant differences in the therapeutic effect of almotriptan
      at the dose studied here. Tolerability of treatments was good throughout the
      entire study period. CONCLUSIONS: Almotriptan 12.5 mg, with or without
      concomitant alcohol ingestion, showed similar plasma concentrations after a
      single dose in healthy volunteers with no clinically relevant drug-to-drug
      interactions.

PMID- 16995334
TI  - Sample size calculations and methacholine challenge tests.

PMID- 16995335
TI  - Successful treatment of anorexia with a combination of high-dose olanzapine,
      fluoxetine and mirtazapine.

PMID- 16995336
TI  - Production and applications of recombinant proteinase 3, Wegener's autoantigen:
      problems and perspectives.
AB  - Antineutrophil cytoplasmic antibodies (cANCA) against conformational epitopes
      ofproteinase 3 (PR3) are regarded as an important pathogenic marker in Wegener's
      granulomatosis (WG). Hence, PR3-based antibody binding assays are widely used for
      diagnosis and monitoring of the disease. Purification of the native catalytically
      active serine protease from granulocytes, however, is relatively inefficient,
      time-consuming and technically demanding. Conformational changes, partial
      aggregation, denaturation during purification and contaminations with inhibitors
      or other proteins from plasma and granulocytes, can affect the quality and
      comparability of PR3-based cANCA determinations. Alternative production of the
      human PR3 autoantigen by recombinant technologies offers several advantages over
      the natural antigen, but the complexity and operating expense of these procedures
      have, so far, delayed the development of new clinical tests. Correct
      posttranslational processing, conformational identity and antigen stability can
      be achieved by the expression of PR3 in Sf9 insect cells and in mammalian hosts,
      HEK293 and HMC-1. Subsequent purification and immobilization of the recombinant
      antigen is furthermore simplified by the attachment of short carboxy-terminal
      peptide tags. In contrast to conventional capture techniques with murine
      monoclonal antibodies, tag-based immobilization of the recombinant antigen does
      not mask portions of the PR3 surface and improves the efficacy of antigen
      coating. Moreover, recombinant PR3 variants will have a great potential to study
      individual anti-PR3 responses and will advance the development of new epitope
      based therapeutics.

PMID- 16995337
TI  - Glomerulonephritis in children with mixed connective tissue disease.
AB  - AIMS: Mixed connective tissue disease (MCTD) has overlapping clinical features
      with systemic lupus erythematosus (SLE). Renal biopsy is necessary for all
      children with SLE to evaluate the prognosis, because they are at a quite high
      risk of developing renal complications. Furthermore, lupus nephritis and
      hypocomplementemia usually precede the appearance of clinical manifestations.
      Immune complex-mediated nephritis is one of the major complications of MCTD.
      Juvenile MCTD is known to be associated with a higher risk of nephritis than
      adult MCTD. However, it is uncertain whether all children with MCTD should be
      subjected to a renal biopsy, and whether most of those with hypocomplementemia
      present nephropathy, as in patients with SLE. We examined the histopathological
      characteristics of juvenile MCTD nephritis, the importance of renal biopsy and
      the implications of hypocomplementemia in our patients and reported cases of
      MCTD. MATERIAL AND METHODS: We performed renal biopsy in 11 children with MCTD
      and found 6 patients with glomerulonephritis. In addition, we studied the
      frequency and the characteristics of glomerulonephritis in 71 cases of juvenile
      MCTD (our 11 patients and 60 reported cases). We also analyzed the relationship
      between hypocomplementemia and pathological features in 41 cases of MCTD
      nephritis (23 adults, 18 children). RESULTS: 6 of our 11 patients had
      glomerulonephritis, but of them four had no abnormality in urinalysis at the time
      of biopsy. In 5 patients renal biopsy showed normal findings. Review of 71 cases
      of juvenile MCTD showed that of them 28% presented latent asymptomatic nephritis
      at the time of biopsy. Membranous nephropathy (MN) and mesangial proliferative
      glomerulonephritis (MPG) were common in MCTD. Interestingly, hypocomplementemia
      was more frequently observed in patients with MN or mixed form of MN and MPG
      (MPG/MN) than simple MPG based on our review of 41 cases (p < 0.01). CONCLUSION:
      A more aggressive indication of renal biopsy should be considered in children
      with MCTD because of the high incidence of non-clinical nephritis. The
      hypocomplementemia observed in patients with MCTD suggests the high frequency of
      glomerulonephritis, including membranous lesions.

PMID- 16995338
TI  - Clinical study of influenza-associated rhabdomyolysis with acute renal failure.
AB  - AIMS: Influenza-associated rhabdomyolysis induces renal failure with a fatal
      outcome. The aim of this study is to evaluate the clinical features, diagnosis,
      and treatment efficacy of influenza-associated rhabdomyolysis patients with acute
      renal failure (ARF). MATERIALS AND METHODS: The subjects included 6 patients who
      had presented with rhabdomyolysis and ARF due to influenza infection on admission
      to our university hospital and its 2 affiliated hospitals between January 2002
      and February 2004. We retrospectively examined the cases. RESULTS: All the
      patients (n = 6) were males, and none of them had received an influenza vaccine.
      The viruses were identified as influenza A (n = 5) and B (n = 1). Muscular
      weakness was observed in many cases (n = 5), whereas pain or tenderness was
      observed in only 1 case (n = 1). For anuric or oliguric patients (n = 4), blood
      purification therapy was performed, while for patients in whom the urine volume
      was normal (n = 2), conservative therapy was administered. CONCLUSION: Careful
      medical attention is necessary when patients have muscle pain and weakness. Early
      recognition of rhabdomyolysis allows prompt institution of an appropriate therapy
      that includes blood purification and may minimize the renal dysfunction
      associated with this disorder.

PMID- 16995339
TI  - Safety of paracentesis in inpatients.
AB  - INTRODUCTION: Prior research has suggested that paracentesis is free from
      complications such as acute renal failure (ARF) providing albumin is
      administered. Actual safety of paracentesis > 1,000 ml was assessed at a tertiary
      care hospital. METHODS: 300 inpatient paracenteses performed between 12/99 and
      4/04 were identified by coding records, of which 40 procedures were excluded due
      to lack of pre- or post-procedure lab values. Charts were reviewed for serum
      creatinine (Scr) before and after procedures, ascites volume, and clinical
      outcomes. RESULTS: 44 deaths occurred after 260 paracenteses (16.9%). Among 33
      patients with ARF, 13 (39.4%) died. Only 31/227 patients without ARF (13.7%) died
      (p < 0.001). Serum creatinine (Scr) > 1.6 mg/dl prior to paracentesis predicted a
      22.5% rate of ARF, compared to 8% for Scr < 1.0 (p = 0.002). ARF increased as
      volume increased (9.9%, 12.4%, and 14.9%, for volumes of < 2,300, 2,300 - 3,200,
      and > 3,200 ml) but this trend did not have statistical significance (p = 0.426).
      ARF occurred in 11/69 (15.9%) of patients receiving albumin, compared to 22/191
      (11.5%) of patients who did not (p = 0.462). CONCLUSIONS: Paracentesis in
      inpatients has significant rates of ARF and death. Scr > 1.6 prior to
      paracentesis predicts an increased rate of ARF. Development of ARF is associated
      with an increased rate of death. No advantage was demonstrated with
      administration of albumin. Pre- and post-paracentesis labwork should be routine
      in inpatients.

PMID- 16995340
TI  - C-reactive protein induced activation of MAP-K and RANTES in human renal distal
      tubular epithelial cells in vitro.
AB  - AIMS: C-reactive protein (CRP) is a component of the acute-phase reaction to
      inflammation, severe tissue injury, and infection. Investigations have shown that
      CRP concentration is highly increased in the urine during acute renal graft
      dysfunction and, therefore, may affect tubular cell metabolism. Nevertheless, no
      data about the effects of CRP on human renal tubular epithelial cells are
      available. METHODS: Human renal distal tubular cells (DTC) were isolated
      immunomagnetically and cultured. Cells were stimulated with affinity
      chromatography pure native CRP from human ascites (10 - 0.001 microg/ml).
      Phosphorylation of MAP-K was assessed by Westernblot analysis. Release of RANTES
      and interleukin-6 was evaluated with an enzyme immunoassay. Cytotoxic effects of
      CRP were determined by a commercially available Live/Dead assay and MTT assay.
      Effects on cell proliferation were analyzed by a fluorimetric assay. RESULTS:
      Westernblot analysis clearly showed that CRP activates the MAP-K pathway of DTC.
      CRP upregulated RANTES expression of DTC in a significant and dose-dependent
      manner. CRP (10 microg/ml) induced a 12.3-fold upregulation, CRP 1 or 0.1
      microg/ml induced a 6.3-/2.8-fold RANTES upregulation, respectively. Interleukin
      6 synthesis was not influenced. Cytotoxic, proliferative or apoptotic effects
      were not observed at the concentrations used. CONCLUSIONS: We demonstrated an
      activating effect of CRP on DTC in vitro. In vivo, this effect of CRP might be
      part of the immune activation cascade during episodes of renal graft rejection or
      bacterial infections.

PMID- 16995341
TI  - Uremic pruritus is associated with higher kt/V and serum calcium concentration.
AB  - BACKGROUND: The prevalence and characteristics of uremic pruritus have not
      recently been investigated in a US dialysis cohort. This study examined uremic
      pruritus and associated risk factors in hemodialysis patients treated in the year
      2005. METHODS: The prevalence and characteristics of pruritus (short version
      McGill pain questionnaire), severity (10 cm visual analogue scale), and effect on
      quality of life (Skindex-16) were determined in thrice weekly hemodialysis
      patients. Daugirdas single-pool Kt/V, clinical and laboratory data were recorded.
      RESULTS: 105 of 307 screened hemodialysis patients met inclusion criteria and
      were evaluated, 49% (151) were excluded due to advanced age, 3% (9) other skin
      diseases, and 14% (42) refused. Participants were 55% male (58/105) and 65%
      African-American (68) with a mean +/- SD age of 48 +/- 11 years. The overall
      prevalence of pruritus was 57% (60/105, 95% CI 47 - 67%) and a positive
      correlation was observed between the presence of uremic itch and serum calcium
      concentration (p = 0.04). Intact PTH and serum phosphorus concentration were not
      associated with either the presence or intensity of itch. Intensity of pruritus
      was positively correlated with increasing months on dialysis (64 +/- 63 vs. 51 +/
      46 months for itch and non-itch, respectively; p = 0.02), higher Kt/V (1.82 +/-
      0.7 vs. 1.70 +/- 0.56 for itch and non-itch, respectively; p = 0.01) and skin
      dryness (p = 0.01). Patients receiving statins were significantly less likely to
      report pruritus (p = 0.02) and uremic itch adversely impacted several aspects of
      quality of life. CONCLUSIONS: Pruritus remains a common and significant symptom
      in adequately hemodialyzed patients. Higher serum calcium concentrations, longer
      durations of ESRD and higher Kt/V appear to be important factors associated with
      uremic pruritus.

PMID- 16995342
TI  - Does loss of residual renal function lead to malnutrition in peritoneal dialysis
      patients?
AB  - OBJECTIVES: It is usually believed that loss of residual renal function is
      associated with anorexia and the development of malnutrition. We conducted a
      retrospective study in our center to evaluate the effect of declining residual
      renal function on patients' nutritional status. METHODS: All incident uremic
      patients (n = 46) who began peritoneal dialysis from January 1, 2003 June 1, 2003
      in our center were closely followed for 1 year with focus on maintaining strict
      volume control with time on dialysis. Patient's residual renal function (RRF) was
      assessed by the average renal urea and creatinine clearances. Those patients who
      had more than 50% decrease in GFR were selected for the present analysis. Serum
      albumin (ALB), dietary protein intake (DPI) and subjective global assessment
      (SGA) were closely followed. RESULTS: There were 16 patients (9 males and 7
      females) included in the present analysis, among whom 31.3% were diabetics.
      Patients' GFR declined significantly (RRF were 4.32 +/- 2.69, 2.99 +/- 2.21 and
      1.24 +/- 0.99 ml/min for Months 1, 6 and 12, respectively, p < 0.05), along with
      a significant decline in urine volume (985.62 +/- 543.29, 698.13 +/- 463.59 and
      425.63 +/- 320.52 ml/d for Months 1, 6 and 12, respectively, p < 0.01). Although
      weekly peritoneal Kt/V did not increase significantly, peritoneal ultrafiltration
      increased significantly during this period (428.75 +/- 408.96, 534.38 +/- 296.39,
      844.38 +/- 440.35 ml for Months 1, 6 and 12, respectively, p < 0.05). Serum ALB
      increased significantly (32.34 +/- 5.07, 34.74 +/- 4.89 and 36.21 +/- 3.98 g/l
      for Months 1, 6 and 12, respectively, p < 0.01). DPI also increased
      significantly. The prevalence of malnutrition (by SGA) decreased from 62.5% at
      the start of dialysis to 18.8% at the end of this study (p < 0.05). CONCLUSIONS:
      Our study suggests that rapid decline of residual renal function in PD patients
      does not necessarily lead to decreased dietary protein intake and deteriorated
      nutritional status. Focus on incremental peritoneal fluid removal along with the
      decline in residual renal function and, thus, maintaining volume control may be
      one of the critical reasons for the success.

PMID- 16995343
TI  - PR3-ANCA-positive crescentic necrotizing glomerulonephritis accompanied by
      isolated pulmonic valve infective endocarditis, with reference to previous
      reports of renal pathology.
AB  - Patients with infective endocarditis (IE) often have renal complications which
      may include infarcts, abscesses and glomerulonephritis (GN). Furthermore, it is
      generally accepted that there is an association between IE and anti-neutrophil
      cytoplasmic antibody (ANCA). Here, we report the case of a 24-year-old man who
      developed rapidly progressive GN in the course of IE due to infection with alpha
      streptococcus. The initial clinical manifestation of the condition was severe
      sacroiliitis without fever. Sandwich ELISA showed that the patient was positive
      for PR3-ANCA at low titer, and the classical complement pathway was also
      activated. Renal biopsy demonstrated several lesions: focal embolic GN, GN with
      immune deposits and focal and segmental crescentic necrotizing GN. Treatment with
      antibiotics and steroids led to eradication of the infection, and resolution of
      the renal disease was accompanied by immediate disappearance of PR3-ANCA and
      hypocomplementemia. During a 4-year follow-up period, no recurrence was observed.
      There have only been 7 case reports of GN associated with IE and PR3-ANCA in
      which the renal pathology has been described, and the current report is the first
      to document renal pathology in a patient with isolated pulmonic valve IE and PR3
      ANCA. Moreover, this report is the first to show a change in renal biopsy
      findings in response to treatment. A review of the 7 literature cases and that of
      our patient showed that none involved pauci-immune GN. Hence, further studies are
      needed to clarify the prevalence of pauci-immune GN in ANCA-positive IE patients.

PMID- 16995344
TI  - A blue kidney--chronic renal failure as a consequence of siderosis in paroxysmal
      nocturnal hemoglobinuria?
AB  - Acute renal failure is a known complication during hemolytic crisis in paroxysmal
      nocturnal hemoglobinuria (PNH). However, chronic renal failure is rare despite
      the well-known spectacular hemosiderosis of the kidneys due to chronic hemolysis.
      Here, we report about a 74-year-old man with PNH who developed acute on chronic
      renal failure after an episode of intercurrent urinary tract infection and
      subsequent hemolytic crisis. Mild chronic hemolysis, well-documented over the
      past decade, had long been considered the cause of a constantly declining
      glomerular filtration rate. Accordingly, magnetic resonance imaging during
      admission demonstrated marked siderosis of both kidneys, supporting the
      hypothesis that chronic renal failure (CRF) was likewise related to PNH. However,
      a renal biopsy revealed acute tubular necrosis and distinct renal siderosis, as
      expected. Additionally, tubulointerstitial injury and global glomerular
      sclerosis, best classified as arterionephrosclerosis, were present. In
      retrospect, these findings were explained by a 15-year history of hypertension
      and a 4-year medication with cyclosporine. Careful diagnostic workup including a
      renal biopsy is mandatory, given a misleadingly suggestive correlation between
      chronic hemolysis and CRF. Chronic renal failure in PNH is a diagnosis of
      exclusion, even if radiologic evidence of heavy siderosis draws off the
      physician's attention.

PMID- 16995345
TI  - Candida glabrata fungemia in a diabetic patient with neurogenic bladder:
      successful treatment with micafungin.
AB  - A 69-year-old man was transferred to our hospital because of fever and acute
      renal failure. 5 weeks prior to admission, he was admitted to another hospital
      and treated with several antibiotics including vancomycin, but fever did not
      subside and renal dysfunction showed rapid progression. On admission, laboratory
      findings revealed pyuria, inflammatory changes, acute renal failure, and
      disseminated intravascular coagulation (DIC). Computed tomography showed left
      ureteral stone and hydronephrosis. Gallium scintigraphy showed avid uptake in the
      left kidney. Serum concentration of vancomycin was 57.4 micro/ml. Candida
      glabrata was isolated from blood, sputum and urine. Under the diagnosis of
      fungemia and left pyelonephritis, he was treated with micafungin (150 mg/day),
      gabexate mesilate and insertion of a double-ended pigtail catheter. The above
      treatment produced regression of systemic inflammation, DIC and acute renal
      failure. At the last follow-up 3 weeks after discharge, ureteroscopy showed that
      the ureter stone had already passed but a soft white-yellowish bezoar was
      detected in the ureter. In this case, neurogenic bladder, poorly controlled
      diabetes, and long-term antibiotic treatment probably enhanced the development of
      C. glabrata infection. Antifungal treatment with micafungin is useful in patients
      with non-albicans Candida infection.

PMID- 16995346
TI  - Biomarker for IgM nephropathy variant and therapy.

PMID- 16995347
TI  - Single-dose daily treatment with cyclosporin A for relapsing nephrotic syndrome:
      report of a case showing poor response.

PMID- 16995348
TI  - A dilemma in treating angiomyolipoma in a horseshoe kidney.

PMID- 16995349
TI  - Anti-calreticulin antibodies in patients with inflammatory bowel disease.
AB  - PURPOSE: Although the pathogenesis of inflammatory bowel disease (IBD) is
      unclear, autoimmune processes seem to play roles in IBD because several types of
      autoantibodies have been found in it. Calreticulin (CRT) is a soluble Ca2+
      binding protein which is present in a wide variety of cells. CRT is localized
      mainly in the endoplasmic reticulum and is often a target for autoantibodies. The
      aim of this study was to evaluate the clinical significance of anti-CRT
      antibodies measured by enzyme-linked immunosorbent assay (ELISA) using the sera
      of patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We
      measured the serum anti-CRT antibodies of 31 Japanese patients with UC and 24
      with CD by ELISA. The controls were 105 subjects: 30 healthy persons, 44 patients
      with primary biliary cirrhosis (PBC), 21 with systemic lupus erythematosus (SLE)
      and 10 with acute colitis (AC). RESULTS: The mean titer of anti-CRT antibodies
      was significantly higher in patients with UC than in healthy individuals (p
      <0.05). The prevalence of anti-CRT antibodies in these patients was significantly
      higher during the initial phase than during the passing phase (p <0.05). In
      patients with CD, the mean titer of anti-CRT antibodies was not significantly
      higher than in healthy individuals. The positivity for anti-CRT antibodies,
      however, was about 30% in those patients, which was as high as in patients with
      UC, SLE and PBC. In patients with AC, anti-CRT antibodies were all negative.
      CONCLUSIONS: The positivity of anti-CRT antibodies may have a diagnostic value
      for IBD, especially in the initial phase of UC.

PMID- 16995350
TI  - A case of hepatic angiosarcoma supplied by both hepatic artery and portal vein.
AB  - Liver neoplasms, whether they are benign or malignant, are usually fed by the
      hepatic artery. We experienced a case of hepatic angiosarcoma supplied by both
      hepatic artery and portal vein. Since there are currently no specific laboratory
      tests to diagnose hepatic angiosarcoma, it is important to detect suspect cases
      from imaging features. This unique hemodynamic property was detected on computed
      tomography (CT) during hepatic arteriography and CT during hepatic
      arterioportography. If any imaging examinations indicate the liver tumor to be
      fed by the portal vein, hepatic angiosarcoma should be suspected.

PMID- 16995351
TI  - Gastrointestinal stromal tumor mimicking gynecological disease.
AB  - Gastrointestinal stromal tumors (GISTs) are common mesenchymal tumors of the
      digestive tract. These tumors occasionally present a pelvic mass and leading to
      the misdiagnosis of gynecologic diseases. Two patients with GIST in the small
      intestine giving an impression of an ovarian fibroma and a uterine leiomyoma
      respectively were diagnosed correctly at the surgery. In the patients with a
      pelvic mass, especially if unusual symptoms and laboratory data being not
      compatible with gynecological disease, the possibility of diseases other than a
      gynecologic disease has to be considered.

PMID- 16995352
TI  - Serotonin syndrome caused by minimum doses of SSRIS in a patient with spinal cord
      injury.
AB  - There have been only a few reports of serotonin syndrome developing after mono
      therapy with a selective serotonin reuptake inhibitor (SSRI). We report a case of
      serotonin syndrome caused by long-term therapy with fluvoxamine prior to
      treatment with paroxetine. An 18-year-old man with spinal cord injury (SCI) at
      thoracic level 2-3 presented with onset of serotonin syndrome after taking
      fluvoxamine (50 mg per day) for 8 weeks prior to treatment with paroxetine (10 mg
      per day) for 6 days. He had confusion, agitation, severe headache, tachycardia
      (124 beats/minute), hypertension (165/118 mmHg), high fever (39.1 degrees C), and
      myoclonus. All of the symptoms disappeared within 24 hours after discontinuation
      of administration of paroxetine. This is an interesting case of serotonin
      syndrome that developed after minimum doses of single therapy with an SSRI in a
      patient with SCI.

PMID- 16995353
TI  - [Blood sugar and pounds down, hardly hypoglycemias. New generation of
      antidiabetics ante portas].

PMID- 16995354
TI  - [Start of insulin therapy. How to ensure patient compliance?].

PMID- 16995355
TI  - [Cardiac decompensation after cesarean section. It could have been heard
      before!].

PMID- 16995356
TI  - [Prevention in family practice. How to motivate the patients to live healthier
      life?].

PMID- 16995357
TI  - [In picking a poisonous specimen taken? Abdominal pain after mushroom meal -- so
      you react right].

PMID- 16995358
TI  - [Natural treatments are in. Probiotics are more than simply yogurt].

PMID- 16995359
TI  - [Therapeutic possibilities of probiotics in antibiotic-related diarrhea].
AB  - One of the major problems associated with the use of antibiotics is the
      occurrence of antibiotic-related diarrhea. Although most such cases of diarrhea
      are harmless, in individual cases it may lead on to fulminant colitis. In 10-20%
      of the patients, the causal factor is infection with Clostridium difficile, which
      multiplies unhindered in patients on antibiotics. In the meantime, controlled,
      randomized studies have shown that probiotics can exercise a preventive effect in
      antibiotic-related diarrhea. The administration of Saccharomyces boulardii or
      Lactobacillus rhamnosus GG reduces the relative risk of an antibiotic-related
      diarrhea developing by 0.5. The data are more uniform in children than in adults.

PMID- 16995360
TI  - [Probiotics in chronic inflammatory bowel disease].
AB  - Current data show that probiotics are more effective in preventing the
      recrudescence of an inflammatory process than in suppressing active disease. This
      is reflected in the solid evidence for the effect of E. coli Nissle 1917
      (Mutaflor) in the maintenance of remission of ulcerative colitis, and of VSL#3 in
      preventing the recurrence of pouchitis. These indications have since been
      incorporated in valid guidelines. Initial clinical studies have also provided
      promising results regarding the efficacy of VSL#3 in preventing pouchitis
      immediately following proctocolectomy.

PMID- 16995361
TI  - [Probiotics in allergic diseases of childhood].
AB  - The increase in allergic diseases in children in the industrialized countries is
      attributed, among things, to the "exaggerated hygiene" in early childhood typical
      of western lifestyle, since insufficient microbial exposure in this phase would
      appear to promote the development of allergies ("hygiene hypothesis").
      Experimental data and initial results of clinical studies show that the immune
      system of infants can be stimulated by the endogenous intestinal flora.
      Probiotics, (apathogenic organisms present in human intestinal flora) have a very
      similar effect: Infants at risk of developing atopy, who, in the first 6 months
      of life received a special probiotic, contracted atopic dermatitis after two
      years only half as frequently as a control group of infants. Therapeutic effects
      were also observed in this clinical condition. For no other allergic
      manifestations have reports so far been published on the successful use of
      probiotics for prevention or treatment.

PMID- 16995362
TI  - [Medication-overuse headache].
AB  - Headache associated with the chronic use of medications has become a significant
      problem in the management of headache. Typically, patients overusing analgesics
      suffer from tension headache, whereas those over-using triptans may experience
      daily migraine-type headaches or an increase in the frequency of migraine
      attacks. The treatment of choice in such cases is withdrawal of the medication
      followed as early as possible by medicinal prophylaxis of the primary headache.

PMID- 16995363
TI  - [Long-term inpatient treatment of extreme juvenile obesity: an 18-month
      catamnestic study].
AB  - Eighteen months after completion of long-term treatment of 98 extremely
      overweight juveniles in the rehabilitation center Insula, this study revealed an
      improvement in the age-specific body mass index (BMI-SDS) in 55.1% of the cases,
      when all the non-responders (approx. 22%) were evaluated as failures. An
      improvement of at least 0.2 or 0.5 BMI SDS points was achieved in 41.8% and
      21.4%, respectively.

PMID- 16995365
TI  - [To change partnership practice into practice partnership. Federal Court stops
      the fee increase].

PMID- 16995364
TI  - [Depressive patients in primary care].
AB  - The study aimed at investigating out-patient treatment of patients with
      depressive disorders referred to a psychiatric hospital by general practitioners
      (GP) and psychiatrists in private practice (PP). Data of the German psychiatric
      basic documentation system (DGPPN-BADO) of all depressive inpatients admitted to
      a psychiatric hospital in 2003 were analysed (n = 360). GP-patients had
      significantly less often a psychopharmalogical treatment before admission than PP
      patients (59.4% vs. 89.7%). GP give significantly less often antidepressive drugs
      than PP do (53.1% vs. 87.9%). 4,7% of GP-patients and 17.9% of PP-patients
      received supportive psychotherapy, special psychotherapeutic treatment regimes
      were seldom in use during outpatient care (4,7% vs. 5,4%).

PMID- 16995366
TI  - [GEZ will shake physicians, too -- protest action runs already. From January on
      one more radio charge!].

PMID- 16995367
TI  - [No joke! University educates professional patients].

PMID- 16995368
TI  - [Cardiac metabolic risk factors. CB1-blocker corrects three with one stroke].

PMID- 16995369
TI  - [Rating of opioids. With rational use for individual treatment goal].

PMID- 16995370
TI  - [Quality of life suffers much in constipation. Plea for an intelligent pain
      therapy].

PMID- 16995371
TI  - [Taiwan strives for the help of WHO. National solo between SARS and avian flu].

PMID- 16995372
TI  - [Dyspnea in an ex-farmer].

PMID- 16995373
TI  - Claiming victory.

PMID- 16995374
TI  - Using an evidence-based process for integrating new healthcare technologies.

PMID- 16995375
TI  - IT can play a critical role in the development of rapid response teams.

PMID- 16995376
TI  - Speaking of Efficiency. West Coast Imaging Center achieves enviable efficiency
      metrics with a planned IT implementation.

PMID- 16995377
TI  - Preparing for interoperability: EHRs and the law.

PMID- 16995378
TI  - Information at the surgeon's fingertips. For one health system, a PACS
      implementation is but a single step in a journey toward improved efficiency and
      patient care.

PMID- 16995379
TI  - In recovery. Supply chain optimization brings benefits to all stakeholders.

PMID- 16995380
TI  - HL7 CDA: The missing link in healthcare IT.

PMID- 16995381
TI  - A redescription of the fish leech Pterobdella amara (= Rhopalobdella japonica)
      (Hirudinida: Piscicolidae) based on specimens from the type locality in India and
      from Australia.
AB  - Pterobdella amara is redescribed from specimens from the type locality in India,
      and from the type host in Queensland, Australia. A neotype is designated from the
      type locality. The presence of conspicuous finlike bodies along the lateral
      margins of P. amara was greatly exaggerated in the original description. The
      trachelosome and anterior portion of the urosome are wide and flat, but there are
      no finlike bodies present. The urosome tapers abruptly posterior to the flattened
      portion, becomes cylindrical, and remains of constant width to the caudal sucker.
      The oral sucker is small and the caudal sucker is terminal. The body is smooth
      and lacks pigmentation, except for 1 pair of eyes on the oral sucker. Important
      internal characters are 2 pairs of mycetomes, 5 pairs of testisacs, confluent
      gonopores, extensive accessory gland cells on the male atrium and ejaculatory
      ducts, a spacious coelom consisting of dorsal and ventral sinuses with expansive
      connections between each at urosome ganglia, and interganglionic expansions of
      the dorsal sinus. Rhopalobdella japonica from stingrays in Japan is synonymized
      with P. amara and becomes a subjective junior synonym. This leech is a parasite
      in the oral cavity of the stingrays Pastinachus sephen and Himantura uarnak in
      India and Australia, and Dasyatis akajei in Japan.

PMID- 16995382
TI  - First report of Gyrodactylus spp. (Platyhelminthes: Monogenea) in the western
      Mediterranean Sea: molecular and morphological descriptions.
AB  - The Gyrodactylus spp. fauna on species of gobies, Pomatoschistus, Gobiusculus,
      and Knipowitschia (Gobiidae: Teleostei), from the western Mediterranean and
      Adriatic seas is strikingly similar to that found in the Baltic Sea and eastern
      Atlantic Ocean, both in morphology and in internal transcribed spacer (ITS) rRNA.
      The fauna consisted of Gyrodactylus branchialis, G. ostendicus, G. gondae, G.
      rugiensis, G. rugiensoides, and G. arcuatus. No new species have been found. A
      morphometric comparison between G. branchialis from the Mediterranean and
      Adriatic seas and its type locality in Ostend (Belgium) showed significant
      differences in ventral bar and marginal hook features. The morphometric variation
      was lower in G. rugiensis, whereas no significant differences were found in G.
      ostendicus. Gyrodactylus branchialis and G. ostendicus collected on P. microps
      were slightly different in the ITS rDNA (-0.6%) compared with specimens on the
      closely related P. marmoratus, probably reflecting ongoing speciation. A hybrid
      zone was identified in the Vaccares lagoon complex (France) where both host
      species are sympatric. There was no clear geographic or host-related pattern in
      the variation found in the ITS2 rDNA in G. arcuatus sampled from P. microps, G.
      flavescens, Pungitius pungitius, K. panizzae, and its original host Gasterosteus
      aculeatus (2 polymorphic sites). Of all studied species, only G. arcuatus, G.
      rugiensis, and G. rugiensoides showed minor intraspecific variation in the ITS
      rDNA. Hence, the physical separation by a shoreline of more than 10,000 km is
      hardly reflected in the parasite ITS rDNA.

PMID- 16995383
TI  - Refractoriness of the western fence lizard (Sceloporus occidentalis) to the Lyme
      disease group spirochete Borrelia bissettii.
AB  - The western fence lizard, Sceloporus occidentalis, is refractory to experimental
      infection with Borrelia burgdorferi sensu stricto, one of several Lyme disease
      spirochetes pathogenic for humans. Another member of the Lyme disease spirochete
      complex, Borrelia bissettii, is distributed widely throughout North America and a
      similar, if not identical, spirochete has been implicated as a human pathogen in
      southern Europe. To determine the susceptibility of S. occidentalis to B.
      bissettii, 6 naive lizards were exposed to the feeding activities of Ixodes
      pacificus nymphs experimentally infected with this spirochete. None of the
      lizards developed spirochetemias detectable by polymerase chain reaction for up
      to 8 wk post-tick feeding, infected nymphs apparently lost their B. bissettii
      infections within 1-2 wk after engorgement, and xenodiagnostic L. pacificus
      larvae that co-fed alongside infected nymphs did not acquire and maintain
      spirochetes. In contrast, 3 of 4 naive deer mice (Peromyscus maniculatus) exposed
      similarly to feeding by 1 or more B. bissettii-infected nymphs developed patent
      infections within 4 wk. These and previous findings suggest that the complement
      system of S. occidentalis typically destroys B. burgdorferi sensu lato
      spirochetes present in tissues of attached and feeding I. pacificus nymphs,
      thereby potentially reducing the probability of transmission of these bacteria to
      humans or other animals by the resultant adult ticks.

PMID- 16995384
TI  - Diclidophora merlangi (Monogenea: Diclidophoridae) on Atlantic cod, Gadus morhua.
AB  - Diclidophora merlangi (Kuhn, in Nordmann, 1832), as species specific to whiting,
      Merlangius merlangus (Linnaeus, 1758), is reported and described for the first
      time on the gills of Atlantic cod Gadus morhua (Linnaeus, 1758). Of the about
      1,200 cod examined in this article, only 2 specimens of D. merlangi occurred on 2
      fish, suggesting that they represented accidental infections. The 2 specimens
      showed specific traits of D. merlangi, but their size was considerably smaller
      than that of D. merlangi on whiting. Principal-component analyses showed that the
      morphology of the specimens on cod was more similar to that of D. merlangi than
      those of other congeneric species from the North Atlantic, additionally
      supporting their assignment to D. merlangi. Quantitative data documenting the
      potential reproductive consequences of D. merlangi occurring on cod is also
      provided. The testes and germaria of the specimens on cod were noticeably smaller
      than those of D. merlangi on whiting, but the number of testes was similar and
      spermatozoa were observed in the sperm duct. By contrast, the aspect and smaller
      size of the oocytes suggested that D. merlangi on cod could not produce viable
      ova, although 1 specimen exhibited an egg with normal sized and shaped capsule.

PMID- 16995385
TI  - First evidence of the presence of microtriches in the Gyrocotylidea.
AB  - The Gyrocotylidea, a small and enigmatic group of intestinal parasites of
      chimaeras, has been considered to be related either to the Monogenea, or, more
      frequently, to the most primitive monozoic tapeworms (Cestoda), i.e., the
      Amphilinidea and Caryophyllidea. The present study, based on transmission
      electron microscopical observations of a species of Gyrocotyle from the rabbit
      fish, Chimaera monstrosa, in the North Atlantic, demonstrates for the first time
      the presence of microtriches as surface structures of gyrocotylideans. Because
      microtriches are considered to be an autapomorphy of tapeworms (Cestoda), in
      which they differ from other Neodermata (Monogenea and Trematoda), the present
      data represent another source of evidence in support of a close relationship
      between the gyrocotylideans and the tapeworms sensu stricto (Eucestoda). Simple
      morphology, small size, and shape uniformity of the microtriches of Gyrocotyle
      sp. may indicate they represent an original (plesiomorphic) form that then
      evolved in more derived cestode groups into a variety of types present mainly on
      the scolex. The microtriches of Gyrocotyle sp. resemble those found in
      caryophyllidean, spathebothriidean, pseudophyllidean, and trypanorhynch cestodes,
      which are considered to represent the most basal groups of the Eucestoda.

PMID- 16995386
TI  - Spermiogenesis and spermatozoon ultrastructure of the cestode Mosgovoyia
      ctenoides (Cyclophyllidea: Anoplocephalidae), an intestinal parasite of
      Oryctolagus cuniculus (Lagomorpha: Leporidae).
AB  - Ultrastructural characters in spermiogenesis and spermatozoa are considered
      important tools to elucidate the phylogenetic relationships within the
      Platyhelminthes. In the Anoplocephalidae, ultrastructural data refer to the
      spermatozoon of 14 species, whereas data on spermiogenesis refer to only 7
      species. The present study focused on the spermiogenesis and spermatozoon of the
      anoplocephalid cestode Mosgovoyia ctenoides, as revealed by transmission electron
      microscopy. Type IV spermiogenesis was detected, beginning with the formation of
      a differentiation zone containing 2 centrioles, with a centriolar adjunct and
      vestigial striated rootlets. Different forms of the latter character have been
      described in other anoplocephalids. This study supports spermiogenesis of type IV
      as the most frequent in the Anoplocephalidae and confirms the presence of a
      centriolar adjunct in yet another type IV spermiogenesis species. The
      spermatozoon of M. ctenoides possesses 1 axoneme of the 9+ '1' trepaxonematan
      type, 2 crestlike bodies, dense plates, and granules of electron-dense
      cytoplasmic material, nucleus, and twisted cortical microtubules. It was again
      confirmed that the presence of granular material and the absence of both a
      periaxonemal sheath and intracytoplasmic walls are constant characters in the
      spermatozoa of all the Anoplocephalinae.

PMID- 16995387
TI  - Alveolar Echinococcus species from Vulpes corsac in Hulunbeier, Inner Mongolia,
      China, and differential development of the metacestodes in experimental rodents.
AB  - Adults of alveolar Echinococcus species with different uterine structures were
      collected from Vulpes corsac in the Hulunbeier Pasture of Northeastern China in
      2001. They were Echinococcus multilocularis Leuckart, 1863 (type No. 3, similar
      to E. m. multilocularis), with vaselike uterus; Echinococcus cf. sibiricensis
      Rausch et Schiller, 1954 (type No. 1), with pyriform uterus; and Echinococcus sp.
      (type No. 2) with spherical uterus at segment top. The metacestode development in
      rodents also differed among those 3 parasites. In the case of E. multilocularis
      (type No. 3), many germinal cells grew on the inner surface of early cysts, most
      of which metastasized into host tissue to form brood vesicles or from the
      germinal cell layer on the inner surface of the vesicle wall. Cells also had an
      appearance of proliferating by means of alveolar buds from alveolar tissue that
      developed outward to form new alveolar foci. In Echinococcus cf. sibiricensis
      (type No. 1), the formation of alveolar vesicles was due to the metastasizing of
      germinal tissue into host tissue; protoscoleces grew in the center of alveolar
      vesicles. In type No. 2 (Echinococcus sp.), the formation of the alveolar vesicle
      was by multiplication of germinal cell layers on the inner surface of alveolar
      cysts; protoscoleces grew from the germinal cell layer and mesh in the vesicles.
      On the basis of uterine structure and on differences in development of
      metacestodes in experimental rodents, we propose that the 3 types of Echinococcus
      represent 3 independent species: E. multilocularis, Echinococcus sibiricensis,
      and Echinococcus sp. (type No. 2-as yet under study).

PMID- 16995388
TI  - Differences in host selection of actinospores of two myxosporeans, Myxobolus
      arcticus and Thelohanellus hovorkai.
AB  - We investigated the host selection mechanism of actinospore stages of 2
      myxosporeans, Myxobolus arcticus and Thelohanellus hovorkai, infecting masu
      salmon (Oncorhynchus masou) and common carp (Cyprinus carpio), respectively.
      Discharge of the polar filaments and sporoplasm release by M. arcticus
      actinospores occurred within the first 5 min of exposure to skin mucus of masu
      salmon. The actinospores also reacted to the mucus of nonsusceptible fish, i.e.,
      sockeye salmon (Oncorhynchus nerka) and goldfish (Carassius auratus), although
      the reactivity was comparatively lower. After exposure of masu, and sockeye and
      chum salmon (Oncorhynchus keta) to M. arcticus actinospores, the penetration of
      sporoplasms was observed in the fins and gills of masu and sockeye salmon to a
      similar extent and to a lesser extent in chum salmon. Thelohanellus hovorkai
      actinospores exhibited a slow response of sporoplasm release to common carp mucus
      as well as penetration into the gills of common carp. Neither chemoresponse to
      mucus of nonsusceptible fish (goldfish and sockeye salmon) nor sporoplasm
      invasion in goldfish was observed for T. hovorkai actinospores. These results
      indicate notable differences in the host selection at the time of entry between
      M. arcticus and T. hovorkai; the former responds quickly to fish mucus with low
      host specificity, whereas the latter was highly host specific in a dilatory
      reaction.

PMID- 16995389
TI  - Equilibrium in lung schistosomula sphingomyelin breakdown and biosynthesis allows
      very small molecules, but not antibody, to access proteins at the host-parasite
      interface.
AB  - The mechanism by which lung-stage schistosomula expose proteins at the host
      parasite interface to nutrient, but not antibody, uptake has been obscure. We
      have found that Schistosoma mansoni and Schistosoma haematobium larvae emerging
      from host lung at a pH of around 7.5, and fixed with diluted formaldehyde (HCHO),
      readily bind specific antibodies in indirect membrane immunofluorescence. Data on
      inhibitors and activators of parasite tegument-bound, magnesium-dependent,
      neutral sphingomyelinase (nSMase), and sphingomyelin biosynthesis inhibitors
      revealed that equilibrium in schistosomular sphingomyelin breakdown and
      biosynthesis prevents antibody binding, yet permits access of small HO-CH2-OH
      polymers to interact with and cross-link proteins at the host-parasite interface,
      allowing for their serological visualization.

PMID- 16995390
TI  - Proinflammatory cytokines in granulomas associated with murine cysticercosis are
      not the cause of seizures.
AB  - Neurocysticercosis is a parasitic infection of the human central nervous system
      caused by the cestode Taenia solium. The most common clinical manifestations of
      neurocysticercosis are seizures. Taenia crassiceps cysticercosis in mice has been
      used as an experimental model for T. solium cysticercosis. Granulomas surrounding
      murine cysticerci have striking immunopathological resemblance to human
      neurocysticercosis; early stage granulomas were able to induce seizures in a
      rodent model. To assess the role of proinflammatory cytokines in early stage
      granulomas, we isolated RNA from murine cysticercal granulomas and checked for
      cytokine expression by reverse transcriptase-polymerase chain reaction (RT-PCR)
      and/or ribonuclease (RNase) protection assays. Cytokine expression was compared
      with histological stages. Interleukin (IL)-1alpha, IL-1beta, IL-1 receptor
      antagonist, and tumor necrosis factor (TNF-alpha) were the major cytokines
      detected in all granulomas. Signals for IL-12, IL-18, and IL-6 RNA were not
      consistently detected and, when detected, were barely demonstrable. Expression of
      migration inhibitory factor (MIF), IL-6, IL-1alpha, TNF-alpha, and IL-18 was not
      significantly different between early and late-stage granulomas. Expression of IL
      1beta, IL-1 receptor antagonist, and IL-12 p40 were higher in late, compared with
      early, stages. Thus, we demonstrated a broad range of cytokines in these
      granulomas. However, we did not document preferential expression of any
      proinflammatory cytokines in early stage granulomas. Thus, proinflammatory
      cytokines are not responsible for the seizures in the rodent model of
      neurocysticercosis.

PMID- 16995391
TI  - Involvement of Manayunkia speciosa (Annelida: Polychaeta: Sabellidae) in the life
      cycle of Parvicapsula minibicornis, a myxozoan parasite of Pacific salmon.
AB  - A coelomic myxozoan infection was detected in freshwater polychaetes, Manayunkia
      speciosa from the Klamath River, Oregon/California, a site enzootic for the
      myxozoan parasites Ceratomyxa shasta and Parvicapsula minibicornis. The
      tetractinomyxon type actinospores had a near-spherical spore body 7.9 x 7.1
      microm, with 3 spherical, protruding polar capsules, no valve cell processes, and
      a binucleate sporoplasm. Parvicapsula minibicornis-specific primers Parvi1f and
      Parvi2r amplified DNA from infected polychaetes in a polymerase chain reaction
      (PCR) assay. The small subunit 18S rRNA gene of the spores was sequenced (GenBank
      DQ231038) and was a 99.7% match with the sequence for P. minibicornis myxospore
      stage in GenBank (AF201375). Chinook salmon (Oncorhynchus tshawytscha) exposed to
      a dose of 1,000 actinospores per fish tested PCR positive for P. minibicornis at
      14 wk postinfection and presporogonic stages were detected in the kidney tubules
      by histology at 20 wk. This life cycle is 1 of only about 30 known from more than
      1,350 myxozoan species, and only the second known from a freshwater polychaete.

PMID- 16995392
TI  - Virulence of Corynosoma constrictum (Acanthocephala: Polymorphidae) in Hyalella
      azteca (Amphipoda) throughout parasite ontogeny.
AB  - Development and growth of parasites depend on resources provided by the host and
      the parasite's ability to use them. Identifying specific costs incurred by the
      host provides insight for assessment of parasite energy budgets, which differ
      among taxa and ontogenetic stages. Data from this study were analyzed using an
      accelerated failure-time model with intensity as a covariate. Results indicated
      significantly reduced survival of amphipods, Hyalella azteca, infected with the
      acanthocephalan Corynosoma constrictum compared with uninfected controls. Male
      and female amphipod survivorship and infection intensity did not differ; however,
      amphipods with high-intensity infections (> 16 larvae) died earlier compared with
      amphipods with low-intensity infections (< 3 larvae). The majority of infected
      amphipods died between 12 and 24 days postexposure, a period of rapid larval
      development. It is hypothesized that host death may be due either to an increase
      in overall larval nutritional demands or to parasite-mediated depletion of a
      specific host substance. Results from this study suggest that developing C.
      constrictum satisfies energy requirements by depriving amphipod hosts of
      resources normally used for somatic growth and maintenance.

PMID- 16995393
TI  - Shape variation of cysticercoids of Hymenolepis diminuta (Cyclophyllidea) from
      fed, partially fed, and fasted Tribolium confusum (Coleoptera).
AB  - Quantitative studies of a crowding effect on cysticercoids of Hymenolepis
      diminuta in the intermediate host are few and limited in scope. In this study, we
      developed a technique to rapidly collect morphological information on large
      numbers of parasites, and verified the utility of geometric models for simple and
      accurate estimation of cysticercoid size for quantitative studies. These models
      were tested using measurements from 4,899 H. diminuta obtained from 666 Tribolium
      confusum exposed 1-4 wk previously. Length, width, and depth of the body and
      cercomer (when present) can be used in conjunction with these models to provide
      the most accurate estimation of parasite size. However, parasite body length
      alone can be used, with adjustment for effects of host diet and infection
      intensity, to predict the remaining measurements in incomplete specimens.
      Parasites that developed in higher intensity infections, or in hosts with reduced
      food intake, were narrower and had a proportionately shorter cercomer. Host age,
      sex, and mating status, and parasite age also had statistically significant, but
      small-magnitude, effects on parasite shape.

PMID- 16995394
TI  - Differential temperature acclimatization responses in the membrane phospholipids
      of Posthodiplostomum minimum and its second intermediate host, Lepomis
      macrochirus.
AB  - The effects of temperature change on phospholipid content in metacercariae of
      Posthodiplostomum minimum and their second intermediate hosts, Lepomis
      macrochirus, were examined to gauge similarities in the homeoviscous adaptation
      of host and parasite membranes to environmental thermal change. Heart, liver, and
      muscle tissues from individual L. macrochirus responded to environmental
      temperature declines with a decrease in the ratio of phosphatidylethanolamine
      (PE) to phosphatidylcholine (PC). Increases in membrane PE concentration increase
      membrane fluidity, maintaining fish membrane function as environmental
      temperature declines. However, the metacercariae of P. minimum exhibit changes in
      cholesterol levels, total lipid levels, and lipid composition (PE/PC) that
      contrast the normal changes for homeoviscous membrane adaptation exhibited by
      their fish intermediate hosts. The parasites seem to rely on their hosts for
      homeoviscous adaptation within normal developmental temperature ranges, pooling
      both cholesterol and PE as energetic stores for development and ontological
      transitions signaled by elevated temperatures.

PMID- 16995395
TI  - Parasites in a biodiversity hotspot: a survey of hematozoa and a molecular
      phylogenetic analysis of Plasmodium in New Guinea skinks.
AB  - A sample of 204 skinks (Squamata: Scincidae) from 10 genera representing 24
      species were collected from 10 different localities in New Guinea and examined
      for blood parasites. Hemogregarines, trypanosomes, microfilarial worms, and 8
      infections showing 2 distinct morphological types of malaria parasites
      (Plasmodium sp.) were observed. Molecular sequence data, in the form of
      mitochondrial cytochrome b sequences from the Plasmodium infections, showed 2
      distinct clades of parasites, 1 in Sphenomorphus jobiense hosts and 1 in Emoia
      spp., which correspond to the 2 morphotypes. There was substantial genetic
      variation between the 2 clades, as well as within the clade of Emoia parasites.
      Nearly half of the skinks sampled had green blood pigmentation, resulting from
      the presence of biliverdin in the plasma; however, only 1 of these lizards was
      infected with Plasmodium sp. and only 2 had any blood parasites. These
      preliminary results suggest a high degree of phylogenetic diversity but a very
      low prevalence of Plasmodium spp. infections in the skinks of this globally
      important biodiversity hot spot.

PMID- 16995396
TI  - Hematozoa of teleosts from Lizard Island, Australia, with some comments on their
      possible mode of transmission and the description of a new hemogregarine species.
AB  - Little is known of the blood parasites of coral reef fishes and nothing of how
      they are transmitted. We examined 497 fishes from 22 families, 47 genera, and 78
      species captured at Lizard Island, Australia, between May 1997 and April 2003 for
      hematozoa and ectoparasites. We also investigated whether gnathiid isopods might
      serve as potential vectors of fish hemogregarines. Fifty-eight of 124 fishes
      caught in March 2002 had larval gnathiid isopods, up to 80 per host fish, and
      these were identified experimentally to be of 2 types, Gnathia sp. A and Gnathia
      sp. B. Caligid copepods were also recorded but no leeches. Hematozoa, found in 68
      teleosts, were broadly hemogregarines of 4 types and an infection resembling
      Haemohormidium. Mixed infections (hemogregarine with Haemohormidium) were also
      observed, but no trypanosomes were detected in blood films. The hemogregarines
      were identified as Haemogregarina balistapi n. sp., Haemogregarina tetraodontis,
      possibly Haemogregarina bigemina, and an intraleukocytic hemogregarine of
      uncertain status. Laboratory-reared Gnathia sp. A larvae, fed experimentally on
      brushtail tangs, the latter heavily infected with the H. bigemina-like
      hemogregarine, contained hemogregarine gamonts and possibly young oocysts up to 3
      days postfeeding, but no firm evidence that gnathiids transmit hemogregarines at
      Lizard Island was obtained.

PMID- 16995397
TI  - Differential expression of calreticulin in developmental stages of Taenia solium.
AB  - Taenia solium, a cestode that causes neurocysticercosis and taeniasis in humans,
      has a complex life cycle. The adult tapeworm develops in the intestine of human
      beings and is also responsible for neurocysticercosis, which is caused by the
      metacestode or cysticercus that develops in the brain. Recently, we have cloned
      the coding region for T. solium calreticulin (TsCRT) as a functional Ca(2+)
      binding protein. Calreticulin is a ubiquitous protein involved in cellular Ca2+
      homeostasis and protein folding. These important functions affect several aspects
      of cell physiology. To explore the expression of TsCRT during the T. solium life
      cycle, we used a specific polyclonal antibody raised against recombinant TsCRT to
      localize this protein by immunolabeling techniques. In sections of cysticerci
      obtained from swine muscle, as well as of adult tapeworms obtained after
      infection of hamsters with cysticerci, TsCRT was preferentially localized in
      tegumentary and muscle cytons of the suckers and rostellum. In mature proglottids
      obtained from infected humans, positive staining was observed in spermatogonia,
      ovogonia, uterine epithelium, and cells of the vas deferens. In the gravid
      uterus, the morula and early stage embryos were highly positive to TsCRT.
      However, expression diminished as embryonic development progressed and was absent
      in fully developed oncospheres that were surrounded by an embryophore. A similar
      down regulation was observed during spermatogenesis. Although early spermatocytes
      showed a high expression of TsCRT, mature spermatozoa present in the vas deferens
      were completely negative. These data indicate that calreticulin expression is
      spatially and temporally regulated during development of T. solium, especially
      during germ cell development and embryogenesis. In addition, these original
      images illustrate, for the first time, these processes at a histological level.

PMID- 16995398
TI  - Molecular cloning and characterization of a 2-Cys peroxiredoxin from Taenia
      solium.
AB  - A Taenia solium 2-Cys peroxiredoxin (Ts2-CysPrx) clone was isolated from a T.
      solium adult cDNA library. The clone encodes a polypeptide comprising 197 amino
      acids with a predictive Mr = 21,836. It has the 2 classical cysteine domains from
      the typical 2-Cys peroxiredoxins, and its primary amino acid sequence shows
      higher identity with 2 Echinococcus 2-Cys peroxiredoxins. Northern and Southern
      blot hybridizations exhibit an mRNA with a size of -1.0 kb, encoded by 1 gene.
      Ts2-CysPrx was expressed in Escherichia coli and purified by anion-exchange
      chromatography. Biochemical analysis showed Ts2-CysPrx is a dimer composed by
      monomers of -22 kDa that presented activity with hydrogen peroxide (H2O2) and
      cumene hydroperoxide. It presented the catalytic mechanism for a typical 2-CysPrx
      because the homodimeric oxidized form is reduced to a monomeric form by
      thioredoxin (Trx) and by dithiothreitol (DTT) and was converted to a homodimeric
      oxidized form by H2O2. Western blot studies using antibodies against Ts2-CysPrx
      revealed that the protein is expressed during the entire T. solium life cycle, as
      in other Taenia species. Immunohistochemical studies indicated that Ts2-CysPrx is
      localized on the tegument and in tegumentary and muscle cells of cysticerci. We
      also show that T. crassiceps cysticerci can tolerate H2O2 levels of 2.5 mM for
      2.5 hr.

PMID- 16995399
TI  - Comparison of gene representation between diploid and triploid Paragonimus
      westermani by expressed sequence tag analyses.
AB  - Expressed sequence tag (EST) analysis of the diploid and triploid Paragonimus
      westermani genes was done to have a rapid and informative outlook of the gene
      expression profiles of the parasites. Totals of 506 and 505 ESTs were generated
      from the diploid and triploid P. westermani cDNA libraries. Based on the BLASTx
      search results of the diploid P. westermani ESTs, 308 (60.9%) matched
      significantly with formerly identified genes and 198 (39.1%) showed no
      significant homology in the GenBank database. A similar homology pattern was
      shown from the triploid EST BLASTx search results with 346 (68.5%) sharing
      homology with previously identified genes and 159 (31.5%) showing no significant
      homology. The EST data from both libraries were analyzed and grouped into 9
      categories. Comparison of the 2 EST pools revealed high similarities among the
      categories of the significantly matched genes. Single genes matched repeatedly
      were also observed in the 2 EST data. Some genes were found that are not yet
      characterized in P. westermani; these genes were matched by both the diploid and
      triploid ESTs. Further study of these genes may provide us with more
      understanding on the parasite's biology and their specific functions in the 2
      strains.

PMID- 16995400
TI  - A new myxozoan parasite from the Amazonian fish Metynnis argenteus (Teleostei,
      Characidae): light and electron microscope observations.
AB  - Myxobolus metynnis n. sp. (Phylum Myxozoa) is described in the connective
      subcutaneous tissues of the orbicular region of the fish, Metynnis argenteus
      (Characidae), collected in the lower Amazon River, near the city of Peixe Boi,
      Para State, Brazil. Polysporic, histozoic plasmodia were delimited by a double
      membrane with numerous microvilli on the peripheral cytoplasm. Several life-cycle
      stages, including mature spores, were observed. An envelope formed by numerous
      fine and anastomosed microfibrils was observed at the spore surface. The spore
      body presented an ellipsoidal shape and was about 13.1 microm long, 7.8 microm
      wide, and 3.9 microm thick. Elongated-pyriform polar capsules were of equal size,
      measuring 5.2 microm in length, 3.2 microm in width, and possessing a polar
      filament with 8-9 turns around the longitudinal axis. The binucleated sporoplasm
      contained a vacuole and numerous sporoplasmosomes. These were circular in cross
      section, showing an adherent eccentric, dense structure, with a half-crescent
      section. Based on the morphological differences and host specificity, we propose
      that the parasite is a new species named Myxobolus metynnis n. sp.

PMID- 16995401
TI  - Description of a new ascarid species in elasmobranchs from Taiwan Strait.
AB  - A new ascarid of elasmobranchs, Terranova amoyensis sp. n., is described from the
      intestine of the red stringray, Dasyatis akajei (Muller and Henle), from Taiwan
      Strait. This is the second report from this genus with a gubernaculum in fish.
      The new species differs from its congeners mainly in the following combination of
      characters: the 3 lips are unequal in size and different in shape, i.e., the
      subventral lips are asymmetric bilaterally and larger than the dorsal lip; the
      latter lip is bilaterally symmetrical. The ventriculus is spherical, and the
      cecum is short relative to the esophagus. Spicules are unequal in size, 1.48 mm
      long for the right spicule and 1.34 mm for the left spicule, or 4.3 and 3.9% of
      body length, respectively. Nineteen pairs of caudal sessile papillae (excluding
      phasmids) are present, of which 13 pairs are precloacal; pairs 14 and 15 lie
      close together on either side of the cloaca, composing ad-cloacal papillae (the
      pair near the tail end are twins). The remaining 4 pairs of postcloacal papillae
      form a group near the tail tip (pair 18 also twins and near the phasmids). The
      gubernaculum is I-shaped. The excretory pore is located on top of a coniform
      prominence whose location is just behind or between the bases of the 2 subventral
      lips. The vulva is prominent at one-third of the anterior part of the body; the
      distance from the vulva opening to the anterior body end is 17.4 mm (13.61
      21.41), 26.8% (25.14-28.93%) of the body length.

PMID- 16995402
TI  - Fay and Rausch 1969 revisited: Babesia microti in Alaskan small mammals.
AB  - The Holarctic distribution of Babesia microti within small rodents implies an
      ancient association. A seminal report of piroplasms in Alaskan voles suggested to
      us the possibility that B. microti entered North America within Eurasian
      microtine rodents dispersing through Beringian corridors. To test this
      hypothesis, we analyzed samples from Alaskan rodents by polymerase chain reaction
      for evidence of infection with B. microti; one-third of the rodents were found to
      be infected. Sequence analysis of the 18S rDNA gene demonstrates that Alaskan B.
      microti comprises a clade that infects microtines in several sites across North
      America and is distinct from a clade that is zoonotic.

PMID- 16995403
TI  - Aspidoderidae from North America, with the description of a new species of
      Aspidodera (Nematoda: Heterakoidea).
AB  - Aspidodera sogandaresi n. sp. (Heterakoidea: Aspidoderidae) from Dasypus
      novemcinctus Linnaeus, 1758 is herein described. This nematode occurs in
      armadillos from as far south as the canal zone of Panama, north through central
      Mexico, and into the southern United States. Previously identified as Aspidodera
      fasciata (Schneider, 1866), this new species has blunt projections on the lips
      and lateral expansions at the distal tips of the spicules, whereas A. fasciata
      has conspicuous digitiform projections on the lips, and a terminal round
      expansion at the tips of the spicules. Other species of the family present in
      North America include Aspidodera binansata Railliet and Henry, 1913; Aspidodera
      vazi Proenca, 1937; and Lauroia trinidadensis Cameron, 1939.

PMID- 16995404
TI  - A new species of glossiphoniid leech from Rana pretiosa (Amphibia: Ranidae) in
      Oregon.
AB  - A new species of ectoparasitic glossiphoniid leech was found feeding on frogs in
      the Nature Center Pond and elsewhere in Deschutes County, Oregon. The new species
      of Placobdella resembles the southern alligator leech, Placobdella multilineata
      Moore, 1953, notwithstanding their vast geographic separation in North America.
      The new species is readily distinguished by possessing subdivided annuli, by its
      papillation and pigmentation patterns as well as by the arrangement of ovarian
      tissues. There is strong evidence of nocturnality and of the potential for
      parasitizing humans.

PMID- 16995405
TI  - Effect of tribendimidine on adult Echinostoma caproni harbored in mice, including
      scanning electron microscopic observations.
AB  - Food-borne trematodiasis is an emerging public health problem with more than 10%
      of the world's population at risk of infection, yet there are only 2 drugs
      available for treatment and morbidity control. We assessed the effect of a
      promising broad-spectrum anthelmintic drug, i.e., tribendimidine, with an
      experimental focus on adult Echinostoma caproni. Female NMRI mice were infected
      with 30 E. caproni for 2 wk and then administered single oral doses of
      tribendimidine ranging between 25 and 500 mg/kg. Three days post-treatment, mice
      were necropsied, and adult worms were recovered from their intestines. Worm
      burden reductions were assessed against untreated control mice. In addition,
      scanning electron microscopic observations were done on adult E. caproni
      recovered from mice given a single dose of 150 mg/kg tribendimidine
      intragastrically 2, 4, and 8 hr post-treatment. Worm burden reductions of 100%
      were achieved at doses of 125 mg/kg and above. Severe damage of the tegument,
      including extensive peeling, formation of blebs, and structural loss of the
      definition of collar and tegumentary spines already occurred within 2 hr after
      drug administration. Our findings call for further investigations using
      tribendimidine in other trematode-animal models, because this compound shows
      promising trematocidal activity.

PMID- 16995406
TI  - Seroprevalence of Toxoplasma gondii antibodies in cats and pigs from rural
      Western Amazon, Brazil.
AB  - Antibodies to Toxoplasma gondii were assayed in sera of 63 cats and 80 pigs from
      71 farms located at Rondonia State, Western Amazon, Brazil, by the modified
      agglutination test (MAT) and the indirect immunofluorescent antibody test (IFAT).
      Antibodies (MAT > or = 1: 25) were found in 55 of 63 cats (87.3%) with titers of
      1:25 in 2, 1:50 in 2, 1:100 in 7, 1:200 in 1, 1:400 in 2, 1:800 in 9, 1:1,600 in
      6, and 1:3,200 or higher in 26 cats. By IFAT, antibodies were found in 55 cats
      (87.3%) with titers of 1:25 in 2, 1:50 in 1, 1:100 in 4, 1:200 in 4, 1: 400 in 1,
      1:800 in 13, 1:1,600 in 12, and 1:3,200 or higher in 18 cats. In pig sera, by
      MAT, antibodies were found in 30 of 80 pigs (37.5%) with titers of 1:25 in 2,
      1:50 in 3, 1:100 in 2, 1:200 in 8, 1:400 in 3, 1:800 in 5, 1:1,600 in 3, and
      1:3,200 or higher in 4 pigs. By using the IFAT (titers > or = 1:64), antibodies
      were found in 35 (43.7%) pigs. The ingestion of undercooked tissues of infected
      pigs can be a source of T. gondii infection for humans and cats. However, the
      high seroprevalence of T. gondii in cats from the Amazon seems most likely to be
      indicative of high contamination of the environment by oocysts.

PMID- 16995407
TI  - Effective protection against experimental Taenia solium tapeworm infection in
      hamsters by primo-infection and by vaccination with recombinant or synthetic
      heterologous antigens.
AB  - The disease caused by Taenia solium is progressively being recognized as a
      growing global threat for public human health and pig husbandry that requires the
      development of effective control measures. A central participant in the
      taeniasis/cysticercosis transmission network is the human carrier of the adult
      tapeworm because of its great potential in spreading the infection. Herein,
      evidence is presented that a primary infection of golden hamsters with orally
      administered T. solium cysticerci improved the host's resistance against a
      secondary infection. Likewise, previous vaccination increased the hamster's
      resistance. Similar high levels of protection (> 78%) were induced by systemic or
      oral vaccination with the S3Pvac anticysticercosis synthetic peptide vaccine or
      the highly immunogenic recombinant chimera based on the protective peptide KETc1
      bound to Brucella spp. lumazine synthase (BLS-KETc1). Increased resistance after
      primo-infection and vaccination possibly results from changes in the immune
      conditions prevailing in the host's intestine. The contribution to protection
      from the KETc1 and BLS epitopes in a chimeric vaccine is under study. Preventive
      vaccination of definitive hosts of T. solium against the tapeworm, the most
      relevant step in the taeniasis/cysticercosis transmission, may greatly impact the
      dynamics of endemic disease and has not been studied or tried previously.

PMID- 16995408
TI  - Reduced taxonomic richness of lice (Insecta: Phthiraptera) in diving birds.
AB  - Avian lice occupy different habitats in the host plumage that the physical
      environment outside the host body may affect in several ways. Interactions
      between host plumage and water may be an important source of such effects. Here,
      we use a comparative approach to examine the effect of a host's diving behavior
      on the taxonomic richness of its lice. Louse genera richness was significantly
      lower in clades of diving birds than on their nondiving sister clades. Species
      richness of host and body mass did not differ significantly between these clades;
      thus, these factors did not bias our results. This study suggests that the hosts'
      diving behavior can effectively influence ectoparasite communities.

PMID- 16995409
TI  - Transfer of Borrelia burgdorferi s.s. infection via blood transfusion in a murine
      model.
AB  - Without antibiotic treatment, the Lyme-disease-causing bacterium, Borrelia
      burgdorferi can be cultured from the peripheral blood of human patients nearly 6
      wk post-tick bite. To determine if Lyme disease spirochetes can be transmitted
      from a spirochetemic donor mouse to a naive recipient during blood transfusion,
      blood taken from immunocompetent infected mice was transfused into either
      immunodeficient (SCID) mice, inbred immunocompetent animals (C3H/HeJ), or outbred
      mice. Nine of 19 (47.7%) immunodeficient mice, 7 of 15 (46.8%) inbred
      immunocompetent mice, and 6 of 10 (60.0%) outbred mice became infected with B.
      burgdorferi after transfusion. Our results indicate that it is possible to
      acquire B. burgdoferi infection via transfused blood in a mouse model of Lyme
      borreliosis.

PMID- 16995410
TI  - Prevalence of antibodies to Toxoplasma gondii in pigeons (Columba livia) in
      Taiwan.
AB  - Starting from January 2004 to December 2004, 665 blood serum samples from pigeons
      (Columba livia) were collected from 44 pigeonaries in 11 counties and 20 regions
      in Taiwan. These samples were examined by latex agglutination test (LAT) for
      antibodies to Toxoplasma gondii by using the LAT. Antibodies were found in 4.7%
      (31/ 665) of pigeons at a LAT titer of 1:32 or higher. The prevalence in Taiwan
      was highest in the northern areas (6.0%; 13/216) and lowest in the eastern areas
      (1.8%; 2/111).

PMID- 16995412
TI  - [Present state of endocrinology in the Czech Republic].

PMID- 16995413
TI  - [Metamorphosis of endocrinology].
AB  - During the last half of century we witnessed not only changes in the definition
      of hormone, in the conception of endocrinology and in understanding of mechanisms
      of hormone action, but also an immense development of technical tools of
      endocrine diagnostic and therapy. Endocrinology has had a profound impact on
      other branches of medicine with the consequence that the frontiers of classical
      endocrinology are slowly vanishing. It is time to ask what will be the future
      demands of patients and whether there will be appropriate number of specialists
      in endocrinology in the near future. Besides the present type of care of the
      patients with endocrinopathies it is necessary to envision a new type of patient
      requesting "comfort therapy", as e.g. improvement of signs of aging, declining
      sexuality, or body height or weight.

PMID- 16995411
TI  - Human thelaziosis--a neglected parasitic disease of the eye.
AB  - The oriental eyeworm, Thelazia callipaeda (Spirurida, Thelaziidae), infects a
      range of definitive hosts, such as dogs, cats, foxes, rabbits, and humans. This
      parasite usually lives under the nictitating membrane of the eye, where the adult
      females release first-stage larvae into the lachrymal secretions; these larvae
      are subsequently ingested by the intermediate arthropod host within which they
      develop to the infective, third-stage larvae. The latter larvae are then
      deposited into the eyes of the definitive host. Recently, T. callipaeda has been
      reported to infect dogs, foxes, and/or cats in Europe (Italy, France, and
      Germany). Human thelaziosis (HT) is considered to be an underestimated parasitic
      disease, whose prevalence appears to have increased in poor socioeconomic
      settings in many Asian countries, including China. In humans, the disease can be
      subclinical or symptomatic, exhibiting epiphora, conjunctivitis, keratitis,
      excessive lachrymation, corneal opacity, and/or ulcers. Knowledge about HT is
      presently fragmentary and mainly limited to clinical case reports. This article
      provides a background on the parasite and its life cycle, reviews cases of human
      thelaziosis, summarizes key aspects regarding the diagnosis of thelaziosis, and
      proposes future research and methods of control of the disease in humans,
      particularly in Asia.

PMID- 16995414
TI  - [Pancreatic hormones and hormonal regulation of insulin secretion].
AB  - Endocrine pancreas producing insulin, glucagon, somatostatin and pancreatic
      polypeptide is under the influence of different types of regulation; among them
      the regulatory role of enteropancreatic axis plays an important role. Incretin
      effect of glucose-dependent insulinotropic peptide (GIP) and glucagon-like
      peptide 1 (GLP-1) is significantly involved in the insulin secretion which is
      modulated by many other hormones. Diabetes mellitus, similarly to disturbances of
      other hormones, can cause impaired regulation of insulin and other pancreatic
      hormones.

PMID- 16995415
TI  - [Regulation of osteoclast activity: a new approach in the therapy of bone
      diseases].
AB  - Bone remodelling is process of constant resorption and formation of a bone.
      Osteoclasts are the cells responsible for bone resorption. Deregulation of
      osteoclast differentiation, activity or function can cause severe diseases, such
      as osteoporosis, osteopetrosis or rheumatoid arthritis. Advances in molecular
      biology of osteoclasts and osteoimmunology open new approaches for the specific
      and efficient therapy.

PMID- 16995416
TI  - [Spontaneous pneumothorax].
AB  - Spontaneous pneumothorax comprises app. 0.1-2 % of surgical diseases. There are
      four subtypes; primary, secondary, catamenial and neonatal. Aetiology of primary
      pneumothorax is not exactly known since there is no direct relation to any basic
      lung disease. Nevertheless, in most patients (80-85 %), it develops due to the
      rupture of an emphysematous bulla or a subpleural air bubble, i.e. blebs. On the
      other hand, secondary pneumothorax is a result or a complication of a verified
      localized or general lung disorder. Catamenial pneumothorax is a recurrent lung
      collapse in women at the time of menstruation. Neonatal pneumothorax is found
      typically in immature or premature newborns, often in association with congenital
      lung disorders. From the pathological point of view, it is an acute disorder of
      distribution of blood gasses in lungs with subsequent hypoxemia, which can be
      identified as an acute thoracic event. The clinical picture of pulmonary collapse
      is characterised by a triad of symptoms++dyspnoea, pleuritic pain and dry and non
      productive cough. The diagnosis is usually determined on the base of history and
      after a careful clinical examination. It is then verified on lung X-ray. The
      objective of therapy of spontaneous pneumothorax is to restore permanent lung
      expansion to the original extent. Conservative treatment is chosen in the first
      episodes of pneumothorax with small extent and without further complications or
      symptoms. In the rest of cases, the surgical treatment is necessary, which
      includes puncture of the pleural cavity, drainage and surgical revision using
      videothoracoscopy or thoracotomy. In general, in case of the first episode of
      pulmonary collapse it is recommended to perform less radical procedure, i.e.
      drainage of the pleural cavity. Recurrences of the disease are indicated for
      surgical treatment; primarily miniinvasive procedures, in which the site of air
      leaking from lung parenchyma is closed and also an artificial pleural symphysis
      is created to prevent recurrence of the collapse. This type of procedure provides
      best results; recurrence is not exceeding 3%.

PMID- 16995417
TI  - [EVI1 and its role in myelodysplastic syndrome, myeloid leukemia and other
      malignant diseases].
AB  - The ecotropic viral integration site 1 (EVI1) gene was identified as a common
      locus of retroviral integration in myeloid tumors found in mice. EVI1 gene is
      highly conserved through evolution and human gene EVI1 on chromosome 3q26 encodes
      zinc fingers-containing transcription factor. EVI1 is expressed in
      nonhematopoietic tissues but not in normal blood or bone marrow. EVI1 was
      detected in hematopoietic cells in retrovirus-induced myeloid leukemias in mice
      and several reports documented EVI1 expression in human myelodysplastic syndromes
      and other hematologic malignancies without 3q26 translocations. EVI1 is
      abnormally expressed in human myeloid leukemias that are associated with the
      t(3;3)(q21;q26), t(3;21)(q26;q22), inv(3)(q21q26) and other chromosomal
      rearrangements. EVI1 is overexpressed in some ovarian cancers and human colon
      cancer cell lines and may play a role in the initiation and/or progression of
      solid tumors, as well as hematopoietic malignancies. EVI1 is a transcriptional
      repressor which inhibits transforming growth factor beta (TGFbeta) family
      signalling by binding signal transducers (Smad proteins) and recruiting
      transcriptional corepressors. TGFbeta is an important regulator of proliferation,
      differentiation, apoptosis and migration of cells. EVI1 inhibits TGFbeta-mediated
      apoptosis. Knockdown of EVI1 function by small interference RNA increases the
      sensitivity of malignant cells to TGFbeta-mediated or other inducer-mediated
      apoptosis. Overexpressed EVI-1 blocks granulocyte and erythroid differentiation
      and possess the ability of growth promotion in some types of cells. EVI1
      functions in some cases as a transcriptional activator which stimulates for
      example GATA2 and GATA3 promoters. The study of EVI1 target genes will help to
      clear the mechanism by which EVI1 upregulates cell proliferation, impairs cell
      differentiation, and induces cell transformation.

PMID- 16995418
TI  - [Arterial hypertension in children and adolescents].
AB  - Hypertension is one of the main risk factors of cardiovascular diseases.
      Hypertension in childhood is defined as blood pressure > or = 95. percentile for
      healthy children population. The prevalence of hypertension in childhood is
      considerably lower than in adults and is about 1%. The aetiology of hypertension
      in childhood differs from adult population--in children secondary forms are more
      common than primary, however, in adolescents primary form already prevails. In
      general, the younger the child and the higher the blood pressure, the more
      probably it is a secondary form of hypertension. The most common causes of
      secondary hypertension are renal diseases (renoparenchymal or renovascular).
      Cardiac diseases (aortic isthmus stenosis), endocrinopathies, central nervous
      system disorders or use of hypertensinogenic drugs are less frequent causes of
      secondary hypertension. Each child with hypertension has to be carefully
      examined; the extent of the examination depends on the age of the child and
      severity of hypertension. The main task for the investigation is to exclude or
      reveal secondary form of hypertension, which could be causally treated (e.g.
      angioplasty in renal artery stenosis). Treatment of hypertension is non
      pharmacological and pharmacological (angiotensin-converting enzyme inhibitors,
      beta-blockers, calcium channel blockers, diuretics, angiotensin receptor
      blockers).

PMID- 16995419
TI  - [Improved control of hypertension and its effect on graft function in children
      after renal transplantation].
AB  - BACKGROUND: Hypertension in patients after renal transplantation (RTx) is
      associated with impaired graft functions and graft survival. Control of
      hypertension in children after RTx is low--only 20-50 % of children have well
      controlled hypertension. The aim of this interventional study is to improve blood
      pressure control and to investigate whether the improved control will improve the
      graft survival. METHODS AND RESULTS: 36 children after RTx (mean age 13.9 +/- 4.4
      years, time after RTx 2.7 +/- 2.4) fulfilled the inclusion criteria. Ambulatory
      blood pressure monitoring (ABPM) and graft function were examined. In children
      with uncontrolled hypertension, the dose and number of antihypertensive drugs
      were increased to reach BP <95th centile. ABPM was repeated after 12 months.
      After 12 months day-time and night-time BP dropped non-significantly, however
      prevalence of uncontrolled hypertension improved significantly from 42 % to 34 %
      (p<0.05). Number of antihypertensive drugs increased from 2.1 +/- 0.9 to 2.4 +/-
      0.8 drugs per patient (p<0.05), namely that of ACE-inhibitors (from 19% to 27%,
      p<0.05). Graft function decreased by 3.6 ml/min/1.73m2/year (p<0.05).
      CONCLUSIONS: This 12 months interventional trial demonstrated that control of
      hypertension in children after RTx can be improved by increasing number of
      prescribed antihypertensive drugs. The decline of graft function was lower
      comparing with previous trials.

PMID- 16995420
TI  - [The use of nitric oxide in the treatment of acute respiratory failure].
AB  - BACKGROUND: Nitric oxide was used as an important selective vasodilator in the
      treatment of acute respiratory failure accompanied with high pulmonary resistance
      in children and adults since late 80's. METHODS AND RESULTS: Paper includes
      remarks about nitric oxide physiology in organism. Group of 33 patients is
      presented (group I 26 newborns, group II 7 children) in which selective pulmonary
      vasodilation with nitric oxide was used. According to response to NO subject were
      classified into subgroups of responders, non-responders. In evaluation of
      oxygenation status OI (oxygenation index, A-a DO2 (alveoloarterial difference)
      and paO2/FiO2 were used. CONCLUSIONS: Significant differences of above mentioned
      values were revealed between responders and non-responders in group I (newborns).
      Significant differences were not revealed in group II (children). Results are in
      accordance with other papers.

PMID- 16995421
TI  - [Auto- and alloreactivity of T lymphocytes in myelodysplastic syndrome].
AB  - BACKGROUND: Successful therapy with ATG and cyclosporine A in some
      myelodysplastic syndrome (MDS) patients led us to study the existence of T cells
      attacking autologous hemopoietic cells. In our study, we attempted to give the
      direct prove of autoreactive T cells in MDS (autoreactivity analysis).
      Simultaneously, we analysed the capacity of MDS patients to respond to allogeneic
      cells from unrelated individuals (alloreactivity analysis). METHODS AND RESULTS:
      Autoreactive lymphocytes directed against own bone marrow mononuclear cells were
      analysed using the modification of cell mediated cytotoxic reaction. With one
      exception we did not confirm the presence of autoreactive T cells among 10
      patients examined. Analysis of alloreactivity was performed by means of standard
      cell mediated cytotoxic reaction and mixed lymphocyte reaction. Surprisingly, the
      cytotoxic response to allogeneic cells was negative in 11 MDS patients from 16
      analysed. When comparing refractory anaemia (RA) and refractory anaemia with ring
      sideroblasts (RARS) patients, the proportion of negative results was higher in RA
      (78 %) than in RARS (40 %). In mixed lymphocyte reaction, the response of MDS
      cells to allogeneic cells of unrelated individual was positive in all tested
      patients. The preliminary testing of TNF and IFNgamma secretion examined in
      supernatants of effector cells showed impaired levels of both cytokines in RA and
      normal levels in RARS in accordance with the findings achieved in alloreactivity
      analysis. CONCLUSIONS: Autoreactive T cells were not found in MDS patients using
      our experimental arrangement. Analysis of alloreactivity showed the defect in
      effector--cytotoxic--phase of cell mediated cytotoxic reaction in the majority of
      MDS patients. The initial phase of this reaction represented in vitro by mixed
      lymphocyte reaction gave normal results. The possible reasons of disturbed
      alloreactivity and its relevance to immunity in MDS are commented in discussion.

PMID- 16995422
TI  - [Extent of tuberculin skin testing spot in bacteriologically verified
      tuberculosis].
AB  - BACKGROUND: Tuberculin skin test was evaluated in patients with bacteriologically
      verified tuberculosis notified in the Czech Republic during 2003 and 2004.
      METHODS AND RESULTS: Out of 1172 patients with bacteriologically verified
      tuberculosis altogether 28.8% were tuberculin-negative. The average value of
      tuberculin reaction in this cohort was 11.6 mm. Among 30-year-old patients with
      bacteriologically verified tuberculosis the number of tuberculin-negative
      individuals was statistically lower (14 %) in comparison with 70-year-old and
      older patients, where the prevalence of tuberculin-negative individuals was 42 %.
      Higher rate of tuberculin-negative individuals with bacteriologically verified
      tuberculosis was found among patients who were diagnosed with liver disease (42 %
      of tuberculin-negative) or malignant tumor (47 % of tuberculin-negative).
      Presented results show that in circumstances of the Czech Republic the tuberculin
      skin test can be used to follow up the spreading of tuberculosis infection in
      younger age groups without accompanying serious disease only. CONCLUSIONS: The
      improvement of the diagnostics of latent tuberculosis infection can bring the
      routine introduction of new tests, e.g. Quantiferon-TB Gold or other methods.

PMID- 16995423
TI  - [Improving self-control in substance dependent persons and pathological gamblers-
      a pilot study].
AB  - BACKGROUND: Impaired self-control is an important symptom of addictive diseases.
      The average number of factors improving self-control among 117 men dependent on
      alcohol, other substances and pathological gamblers was 5.55 (SD=3.5). METHODS
      AND RESULTS: We classified strategies how to improve self-control into following
      groups (their ordering reflects the frequency of their use in our sample): 1. The
      help of others (professional treatment, self-help groups, and family), 2.
      Distraction and similar techniques, 3. The use of motivation, 4. Life-style
      changes including appropriate rest, 5. Physical activity, sports, physical work,
      6. The use of environments, 7. Mastering of social and other relevant skills, 8.
      Relaxation based approaches, 9. Techniques working with improved self-awareness,
      10. Pharmacotherapy, 11. Acknowledgement of an addictive disease and abstinence,
      12. Disrupting risky behavioral patterns. CONCLUSIONS: To improve of self-control
      in addictive diseases simple techniques are appropriate because of temporarily
      impaired cognitive functions during craving. Frequent repetition are also
      important.

PMID- 16995424
TI  - [Use of external photoprotective agents in children living in the area of
      Prague].
AB  - BACKGROUND: Development of skin melanoma is related to the higher exposition to
      ultraviolet light, namely to the repeated sun burning of children. Because no
      valid information on the use of photoprotection in children can be found, an
      extensive search on the use of such measures, their galenic form and protective
      features was undertaken in order to evaluate the situation and to suggest
      necessary improvements. METHODS AND RESULTS: A group of 140 children aged 3 to 15
      years, part of the group living in Prague, another part living outside the city
      was examined whether they use some local photoprotection during longer exposition
      to sun. If the answer was positive, it was followed in which season the
      photoprotection is used and whether it was used repeatedly. We also questioned on
      the forms of the local photoprotectives and the value of solar protective factor.
      CONCLUSIONS: Beside the description of sun tanning characteristics of children,
      we were informed by their parents that 59% of children use the photoprotection
      regularly, 41% only occasionally. The age of the first use of protection was 3.75
      years. Photoprotection was used once a day in 28% of children, repeated use
      (during bathing, seashore stay, tourism) was reported in 72% of cases. The
      galenic form of photoprotective was most frequently a sun tanning creme (42%), a
      sun tanning milk (30%), both forms alternatively (8%), an oil (8%) or some other
      form (14%). The value of photoprotective factor was reported by 108 out of 131
      parents and it was less than 10 in 9 children, 11 to 22 in 60 children, 21 to 40
      in 36 children and over 40 in 3 children.

PMID- 16995425
TI  - [Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)].
AB  - BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a
      disorder with autosomal recessive inheritance caused by mutations in the gene
      encoding thymidine phosphorylase (TP). TP deficiency results in imbalance of
      mitochondrial pool of nucleotides leading secondary to multiple deletions and
      depletion of mitochondrial DNA (mtDNA) and impairment of oxidative
      phosphorylation system. The disease is clinically characterized by
      gastrointestinal dysmotility with symptoms of pseudo-obstruction, severe failure
      to thrive, ptosis, leukoencephalopathy, peripheral neuropathy and myopathy. We
      present results of the clinical, histochemical, biochemical and molecular
      analyses of the first Czech patient with MNGIE syndrome. METHODS AND RESULTS:
      Man, 33-years old with twenty-year history of failure to thrive (height 168 cm,
      weight 34 kg) and progressive gastrointestinal dysmotility, external
      ophthalmoplegia, leucoencephalopathy and peripheral neuropathy was recommended to
      metabolic center. Histochemical analyses in muscle biopsy showed the presence of
      "ragged red fibers" with focal decrease of cytochrome c oxidase activity, but
      spectrophotometric analyses in isolated muscle mitochondria revealed normal
      activities of all respiratory chain complexes. Metabolic investigation revealed
      markedly increased plasma level of thymidine (6.6 micromol/l, controls <0.05
      micromol/l) and deoxyuridine (15 micromol/l, controls <0.05 micromol/l). The
      activity of TP in isolated lymphocytes was low (0.02 micromol/hour/mg protein,
      reference range 0.78 +/- 0.18). Molecular analyses in muscle biopsy revealed
      multiple mtDNA deletions and homozygous mutation 1419G>A (Gly145Arg) was found in
      gene for TP. Both parents are heterozygotes. CONCLUSIONS: MNGIE has to be
      considered in patients presenting with a combination of gastrointestinal and
      neurological symptoms. Plasma level of thymidine may serve as the best method for
      laboratory screening of MNGIE, but molecular analyses are necessary for genetic
      counselling and prenatal diagnosis in affected families.

PMID- 16995426
TI  - [Meconium ileus as a first symptom of cystic fibrosis in a newborn].
AB  - The authors present a case of cystic fibrosis in a newborn. The first symptom of
      cystic fibrosis in this case was meconium ileus. They describe correct diagnostic
      method of ileus in newborn, consecutive operation and last but not least they
      show necessity of follow-up investigations to verification of cystic fibrosis.

PMID- 16995427
TI  - [History of foster care in the Czech Republic].
AB  - "The enlightment period" in the second half of the 18th century brought new view
      on the negative results of the institutional care in orphanages. The aim to
      improve the care of orphans and unattended children in the region of former
      Austrian Empire resulted in the year 1789 in the new law about the foster care.
      The law incorporated ten principles how to provide, control and finance the
      foster care in our region.

PMID- 16995428
TI  - [Evidence for the neuroprotective properties of afobazole in experimental model
      of focal brain ischemia].
AB  - The neuroprotective effect of the new selective anxiolytic afobazole was
      evaluated in rats with ischemic stroke produced by the occlusion of the left
      middle cerebral artery, with simultaneous ligation of the ipsilateral carotid
      artery. Afobazole exhibits a protective effect in a dose range from 0.1 to 5.0
      mg/kg for the first injection delayed 24 h after operation and double daily
      injections over the following two days.

PMID- 16995429
TI  - [Antistressor and analgesic effects of mexidol, diazepam, paracetamol, and their
      combinations].
AB  - Mexidol (100 and 200 mg/kg) and diazepam (1 and 2 mg/kg) exhibit a dose-dependent
      antistressor effect in the pain expectation stress test in rats (conditional
      emotional reflex). The effect is manifested by the normalization of both motor
      and somatovegetative characteristics. Paracetamol in a dose of 50 and 100 mg/kg
      does not possess antistressor properties. Both mexidol and paracetamol increase
      the threshold of pain sensitivity in the test with electric stimulation of tail
      in rats. Diazepam does not reduce the pain threshold in this test. The combined
      administration of mexidol or diazepam with paracetamol does not change the
      antistressor effect as compared to that of each drug alone. Mexidol, but not
      diazepam, enhances the effect of paracetamol on the pain threshold.

PMID- 16995430
TI  - [Pilot clinical trial of ladasten].
AB  - The psychotropic actibn and efficacy of ladasten, a new psychostimulant with
      anxiolitic activity, was studied in a standard clinical trial involving therapy
      of patients with psychogenic asthenic disorder. Ladasten exhibits a unique
      combination of therapeutically significant stimulant and anxiolytic effects,
      which is unusual of psychostimulants. At the same time, the results of ladasten
      action upon single administration on the dynamics of psychopatological disorders
      and psychological self-test indexes show that the psychostimulant action is
      predominating. The established combination of the psychostimulant and anxiolytic
      effects of ladasten is optimal for the therapy of patients with psychogenic
      asthenic disorders. Ladasten shows high efficacy in the treatment of these
      disorders testify and has good prospects for practical application.

PMID- 16995431
TI  - [Neuroprotective activity of the proline-containing dipeptide noopept on the
      model of brain ischemia induced by the middle cerebral artery occlusion].
AB  - The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) on
      the extent of ischemic cortical stroke was investigated in experiments on white
      mongrel male rats with ischemia induced by a combination of the middle cerebral
      artery occlusion with ipsilateral common carotid artery ligation. Animals were
      treated with noopept (0.5 mg/kg, i.p.) according to the following schedule: 15
      min and 2, 24, and 48 h after the occlusion. Test rats were decapitated 72 h
      after occlusion, brains were extracted and frozen, and thin brain slices were
      stained with 2,3,5-triphenyltetrazolium chloride. The slices were scanned and
      processed using Auc 1 computer program, which estimates the percentage of damaged
      area relative to that of the whole ipsilateral hemisphere. The conditions of
      coagulation the distal segment of middle cerebral artery were selected, which
      caused necrosis localized in the fronto-parietal and dorso-lateral regions of the
      brain cortex without any damage of subcortical structures. The extent of the
      brain damage in control group (treated by saline) was 18.6%, while that in the
      group treated with noopept was 12.2%, thus demonstrating a decrease in the
      infarction area by 34.5% (p < 05). The data on noopept efficacy on the model of
      the extensive ischemic injury of brain cortex show that this drug has good
      prospects for use in the neuroprotective treatment of stroke.

PMID- 16995432
TI  - [Neuroprotective effect of antipsychotic drugs (neuroleptics) in global brain
      ischemia].
AB  - Most of typical and atypical neuroleptics belonging to various chemical groups
      produce a significant, dose-dependent increase in the brain tolerance to global
      ischemia. This activity of neuroleptics is related to their structure and
      exhibits no correlation with their antipsychotic properties. Therefore, the
      ability to increase the brain tolerance to global ischemia is an independent
      property of neuroleptics. The neuroprotective effect is also not correlated with
      their affinity to serotonin 5-HT2A and dopamine D2 receptors, but is closely
      related to the development of deep hypothermia. Thermoneutral conditions prevent
      both effects. Tolerant strategy plays the main role in the development of the
      neuroprotective effect of neuroleptics.

PMID- 16995433
TI  - [Cardioprotective effect of GABA derivatives in acute alcohol intoxication].
AB  - Cardioprotective properties of GABA analogs under conditions of acute alcoholic
      intoxication have been studied using the following functional tests: volume
      loads, tests for adrenoreactivity, and maximum isometric load. The experiments
      showed that a 32% aqueous ethanol solution intraperitoneally injected in a dose
      of 8 g/kg produces a cardiotoxic action, which is manifested by a decrease in the
      inotropic reserve in load tests. Citrocard (50 mg/kg), phenibut (50 mg/kg), and
      piracetam (200 mg/kg) prevent the alcohol-induced myocardium injury, as shown by
      the heart contractility retained on a higher level in the test group than in the
      control group.

PMID- 16995434
TI  - [Comparative analysis of antiarrhythmic and proarrhythmogenic effects of drugs
      for neuroleptanalgesia, ataralgesia, and antidepranalgesia in experimental acute
      myocardial infarction].
AB  - Proarrhythmogenic and antiarrhythmic effects of drugs for neuroleptanalgesia
      (NLA), ataralgesic (ATA) and antidepranalgesia (ADA) in chronic experiments on
      sleepless rabbits with acute myocardial infarction, with and without
      tachyarrhythmias, were studied using ECG, intraventricular electromanometry and
      tetropolar rheography. NLA (phentanylum, 1 microg/kg + droperidol, 5 microg/kg),
      ADA (pyrazidole, 1 mg/kg + tramal, 1 mg/kg) and ATA (diazepam, 1 mg/kg + promedol
      0.5 mg/kg) produce antiarrhythmic effect with maximum manifestation of NLA on the
      3rd day, and of ATA and ADA on 3-5th day. This medication increased blood supply
      and contractility of ischemic myocardium. Proarrhythmogenic effects of this
      medication were not observed.

PMID- 16995435
TI  - [Acute and chronic amiodarone effects on the dynamics of force-interval
      relationship in rat papillary muscle].
AB  - Effects of acute and chronic amiodarone treatment on the force-interval
      relationship were investigated in rat papillary muscle. It was found that both
      acute and chronic amiodarone treatment decreased the amplitude of extrasystoles.
      At the same time, only short-term administgration of amiodarone increased
      postextrasystols and post-rest potentiations of twitch force in rat myocardium.
      It is concluded that the acute and chronic amiodarone treatment suppress the
      excitability of cardiomyocytes, but only the chronic treatment increases the
      effective refractory period. The results suggest that the acute administration of
      amiodarone can influence the intracellular calcium homeostasis.

PMID- 16995436
TI  - [Influence of the structure of synthetic gestagens on their binding to
      progesteron receptors in the endometrium].
AB  - Chemical modification of progesterone molecule leads to changes both in the
      gestagenic activity of new derivatives and in their specific binding with
      progesterone receptors. The passage from esters (acetomepregenole, butagest) to
      the corresponding OH-forms such as 17a-acetoxy-3b-hydroxy-6-methyl-pregna-4,6
      dien-20-one (ABMP)is accompanied by an increase in the binding with progesterone
      receptors in vitro. The translocation of a double bond from endocyclic (N6-N7) to
      exocyclic position (methylene group at N6 in ABMP) has no significant effect on
      the ability to binding with progesterone receptors.

PMID- 16995437
TI  - [Effect of RGD-containing peptides on platelet aggregation].
AB  - The influence of new synthetic peptides ARGDS-NH2 and RGD-dFK (synthesized by the
      fermentative method) and VPNLRGDLQVLA (a fragment of the foot-and-mouth virus's
      surface peptide) on the ADP-induced human platelet aggregation in vitro was
      studied. All peptides were found to inhibit the human platelet aggregation, but
      the synthetic peptides (ARGDS-NH2 and RGD-dFK) showed the most pronounced effect.
      Significant decrease in the platelet aggregation was observed at their
      concentrations within 0.1-10 mM. ARGDS-NH2 and RGD-dFK inhibited the platelet
      aggregation stronger than the reference drug pentoxifylline at equivalent
      concentrations.

PMID- 16995438
TI  - [Genomic and extragenomic mechanisms of antiglucocorticoid action of gestagens on
      thymocytes].
AB  - Effects of a new synthetic progesterone derivative 17a-acetoxy-3b-butanoyloxy-6
      methyl-pregna-4,6-dien-20-one (ABMP) and the reference gestagen preparations on
      the rat thymus were evaluated by the degree of variation of the intracellular
      levels of calcium and cAMP, 3H-uridine inclusion into RNA, thymocyte viability,
      and thymus mass. It is shown that gestagens can produce antiglucocorticoid action
      on thymocytes, this activity being most pronounced in the case of ABMP.

PMID- 16995439
TI  - [Effect of afobazole on the accumulation of free radical oxidation products and
      the catalase activity in rats with cerebral ischemia].
AB  - The influence of afobazole on the accumulation of free radical oxidation products
      (reactive oxygen species, ROS) and on the activity of antioxidative enzyme
      catalase was studied in striatum and cortex of rats under cerebral ischemia
      damage conditions. Afobazole showed a tendency to decrease the extent of ROS
      accumulation in the cortex. In striatum, the intensity of ROS accumulation in
      rats after ischemia wasa reliably lower as compared to that in control rats, but
      afobazole produced a partial recovery of this parameter. Afobazole induced an
      increase in the catalase activity in the cortex of rats with ischemia. In
      contrast, afobazole did not change the activity of this enzyme in striatum (where
      it was also decreased by ischemia). Thus, afobazole increased the resistance of
      neuron membrane structures to free radical oxidation in cortex and striatum and
      stimulated the catalase activity in the cortex in rats with global reversible
      cerebral ischernia.

PMID- 16995440
TI  - [Pharmacological correction of energy metabolism disturbance in the inflammatory
      dystrophic process in the periodontium].
AB  - The influence of lipoic acid on the energy homeostasis in rats with chronic
      generalized parodontitis has been investigated. Lipoic acid possesses the energy
      saving activity, which is related to an increase in oxidative phosphorylation
      efficiency.

PMID- 16995441
TI  - [The main pharmacokinetic parameters of p-tyrosol upon intravenous injection in
      rats. II. Verification of the pharmacokinetics linearity and evaluation of the
      possible accumulation].
AB  - The main pharmacokinetic parameters of p-tyrosol after single (in 3 doses) and
      repeated intravenous injection were studied in rats. The content ofp-tyrosol in
      the blood plasma was determined by spectrofluorimetric method. The
      pharmacokinetic parameters of p-tyrosol are linear in the dose range from 50 to
      200 mg/kg. Repeated administration leads to accelerated metabolic elimination of
      p-tyrosol.

PMID- 16995442
TI  - [Effects of antidepressants in models of brain self-stimulation and place
      preference after prolong social isolation and alcoholization].
AB  - In rats rearing in social isolation since 17th day of life and treated with 5-15%
      ethanol solution within 3 months, the effects of antidepressants on self
      stimulation of lateral hypothalamus and place preference were studied. The
      comparative study of seven antidepressants with different mechanism of action
      (fluoxetine, maprotiline, tianaptine, pyrazidol, sertraline, citalopram,
      mianserin) was shown that pyrazidol and tianeptine and in a less degree
      sertraline and citalopram possessed the significant antidepressant activity in
      the model of social isolation and maprotiline and tianeptine did in model of
      alcoholization. It is concluded that antidepressants studied activate the
      reinforcing properties of the brain, that is associated with the involvement of
      both the catecholamine and serotonin system, working reciprocally.

PMID- 16995443
TI  - [Effect of biologically active substances of animal and plant origin on
      prooxidant-antioxidant balance in rats with experimental prostatic hyperplasia].
AB  - The effect of biologically active complexes of animal (prostatilen) and plant
      (permixon) origin on physiological indices of prostate and prooxidant-antioxidant
      balance in prostate and blood was studied in rats with the hyperprolactinemia
      induced prostatic hyperplasia. It was shown that both prostatilen (1 mg of the
      total peptides per kg) and permixon (100 mg of Serenoa repens extract per kg)
      prevent increase in the prostate mass and volume, in the content of lipid
      hydroperoxides, and in the glutathione peroxidase activity in prostate.
      Prostatilen, in contrast to permixon, normalized the content of lipid
      hydroperoxides (increased under hyperplazia conditions) and increases glutathione
      peroxidase activity (reduced under hyperplazia conditions).

PMID- 16995444
TI  - [Antiarrhythmic properties of opioid receptor agonists].
AB  - Data on the antiarrhythmic properties of opioid receptor (OR) agonists have been
      systematized. An analysis of published works which indicate that opioids increase
      cardiac tolerance to arrhythmogenic influences both in vivo and in vitro has been
      performed. For example, occupancy of central micro- and delta-OR and also ORL1
      receptors increases cardiac tolerance to arrhythmogenic action epinephrine and
      aconitine. In contrast, activation of central kapa-OR exacerbates arrhythmogenic
      action epinephrine. Stimulation of peripheral delta2- and kappa1-OR decreases an
      incidence of arrhythmias induced coronary artery occlusion and reperfusion in
      vivo. Occupancy of peripheral micro-, kappa2-, delta1-OR and also ORL1 receptors
      has no effect on the cardiac tolerance to arrhythmogenic action of ischemia and
      reperfusion but increases cardiac electrical stability in rats with post
      infarction cardiosclerosis. Authors suggest that opioids which unable penetrate
      to blood barrier may be used for therapy of arrhythmias.

PMID- 16995445
TI  - The influence of accessory right inferior hepatic veins on the venous drainage in
      right graft living donor liver transplantation.
AB  - BACKGROUND/AIMS: Proper venous outflow reconstruction is essential for the
      success of living donor liver transplantation (LDLT). It has also a decisive
      impact on postoperative graft dysfunction. The accessory right inferior hepatic
      veins (IHVs) usually drain parts of the lateral sector of the right hemiliver
      graft (RHL). The purpose of our study was to: (1) evaluate the drainage patterns
      of the IHVs in right hemiliver grafts; (2) analyze the influence of IHVs on the
      dominance relationships between the right and middle hepatic veins in RHL's; (3)
      evaluate some potential correlation between drainage patterns of IHVs and the
      portal vein anatomy. METHODOLOGY: We analyzed 3-dimensional CT-imaging
      reconstructions of 71 potential live liver donors evaluated at our Institution
      between January 2003 and October 2004. RESULTS: (1) Thirty-six (51%) donors had
      inferior hepatic veins (IHV) with detectable venous drainage territories, (2) the
      RHV/IHV-complex was dominant in 97% of cases, and the RHV as a single veinwithout
      anatomical IHV was dominant in 94% of right hemiliver grafts, (3) 27 of 71 livers
      (38%) showed a central (n=11) or peripheral (n=16) PV anomaly, (4) IHV provided a
      mean 32% of venous drainage in the right lateral sector, and in some cases
      drained up to 25% of the right medial sector irrespective of the PV anatomy, (5)
      such cases required IHV reconstruction to prevent severe tissue congestion in the
      right hemiliver graft. CONCLUSIONS: Accurate insight into the drainage patterns
      of the right and middle hepatic veins and precise knowledge of the functional
      volume drained by the IHV are essential when planning for the proper outflow
      reconstruction of right hemiliver grafts in LDLT.

PMID- 16995446
TI  - Distinct gene expression profiles in gastric epithelial cells induced by
      different clinical isolates of Helicobacter pylori--implication of bacteria and
      host interaction in gastric carcinogenesis.
AB  - BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection is a major risk factor
      of peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid tissue
      (MALT) lymphoma. The interplay between H. pylori and host is an important issue
      for elucidation of pathogenesis of H. pylori-related diseases. We aimed to
      examine simultaneously dynamic changes of multiple molecular pathways of
      infection affected by different H. pylori strains by cDNA microarrays.
      METHODOLOGY: To elucidate the cross-talk between H. pylori and gastric epithelial
      cells, we isolated three different H. pylori strains from patients with gastric
      cancer (GC), duodenal ulcer (DU), and gastric MALT lymphoma (MA). The bacteria
      were co-cultured with gastric epithelial cells (AGS) and total RNAs were
      extracted from AGS cells and used for detection of genes represented in the
      microarray. RESULTS: Of the 12,814 clones on the microarray, there were 522 genes
      expressed differently in the three groups. Of the 522 genes, there were 4 genes,
      4 genes and 13 genes, either up- or down-regulated more than twofold change, in
      AGS cells induced specifically by GC, MA, and DU strain, respectively. The GC and
      DU strains induced more genes involving in carcinogenesis, such as pim-1, jun B,
      and VEGF. CONCLUSIONS: Our data by cDNA microarray suggest bacterial factors may
      determine the outcomes of H. pylori infection. The expression profiles of cDNA
      microarray provide clues for diagnosis, treatment, and prevention of H. pylori
      related gastroduodenal diseases.

PMID- 16995447
TI  - Effect of percutaneous biliary drainage on serum levels of tumor markers in
      patients with obstructive jaundice.
AB  - BACKGROUND/AIMS: Some tumor markers such as CA 19-9 are shown to be increased in
      obstructive jaundice due to either benign or malignant causes. In this study the
      clinical importance of raised serum levels of tumor markers have been evaluated,
      with particular reference to obstructive jaundice and percutaneous biliary
      drainage. METHODOLOGY: We conducted a prospective longitudinal before-after
      trial. Twenty-one patients with obstructive jaundice were investigated, 5 with
      benign obstruction and 16 with malignant disease. All patients were examined with
      abdominal CT prior to biliary drainage. All patients underwent percutaneous
      transhepatic cholangiography, and 20 of 21 patients underwent percutaneous
      biliary drainage within 3 days after the CT examination. RESULTS: The mean CA 19
      9 at presentation was lower in the group with benign disease (95 +/- 60.9 IU/mL)
      than those with malignancy (461.9 +/- 331.4 IU/mL). The mean CA 19-9 level in the
      benign group 1 week after drainage was 12 +/- 11.8 IU/mL. The mean CA 19-9 level
      in the malignant group after drainage was 249.7 +/- 279.5 IU/mL. CONCLUSIONS: A
      prominently high serum CA 19-9 level at the presentation and a high serum CA 19-9
      level after successful biliary drainage should prompt investigation for a
      malignant etiology of obstructive jaundice.

PMID- 16995448
TI  - Costs and benefits of laparoscopic cholecystectomy: abdominal wall lifting vs.
      pneumoperitoneum procedure.
AB  - BACKGROUND/AIMS: Gasless laparoscopic surgery using the abdominal wall lifting
      (AWL) method was first developed in Japan and has been used in various surgical
      fields. The AWL method allows the use of conventional reusable surgical
      instruments. The purpose of this study was to compare the cost-effectiveness of
      laparoscopic cholecystectomy (LSC) using the AWL method in relation to that using
      pneumoperitoneum (P) method. METHODOLOGY: Retrospective analysis of 431 LSC
      procedures between 1991 and 2004 was performed. The two surgical groups consisted
      of consecutively operated patients with a diagnosis of cholecystolithiasis or
      gallbladder polyps. One group consisted of 224 LSC procedures performed using the
      P method from 1992 to 1998 and the other group comprised 207 LSC performed using
      the AWL method from 1998 to 2004. All instruments used in the P method were
      disposable, whereas trocars, scissors, dissectors, graspers and L-hook electrodes
      (excluding clips) used in the AWL method were reusable. Hospital expenses, length
      of hospital admission and complication rates were analyzed. RESULTS: Mean
      hospital cost per case for LSC using the AWL method (dollars 6743) was 7% less
      expensive than that using the P method (dolars 7215). Costs of operative
      equipment contributed to the difference (mean dollars 912 per case) in total
      cost. Conversion to open cholecystectomy occurred in 6 cases (2.9%) using the AWL
      method and 7 cases (3.1%) using the P method. There were no significant
      differences in length of hospital admission or complication rates between the two
      groups. CONCLUSIONS: LSC using AWL method was less expensive than that using P
      method. This is mainly due to the use of reusable instruments in the AWL method.
      If LSC is performed using the AWL method instead of using disposable equipment,
      considerable savings can be achieved without compromising patient safety.

PMID- 16995449
TI  - Endoscopic therapeutics for patients with cholangitis caused by the
      juxtapapillary duodenal diverticulum.
AB  - BACKGROUND/AIMS: The role of endoscopic intervention for cholangitis caused by
      the juxtapapillary duodenal diverticulum without choledocholithiasis, i.e., the
      Lemmel's syndrome remains controversial. The aims of the study were to
      characterize these patients and evaluate endoscopic therapy for Lemmel's
      syndrome. METHODOLOGY: This study retrospectively reviewed 1923 endoscopic
      retrograde cholangiopancreatograms of patients with cholangitis during a three
      year period, and 337 of these patients with juxtapapillary duodenal diverticula
      were included. Two groups (i.e., one with and one without Lemmel's syndrome) were
      compared. RESULTS: Lemmel's syndrome was diagnosed in 39 patients (39/337,
      11.6%). Both groups had similar cannulation success rates (94.9% vs. 87.9%, p =
      0.28) and complication rates (2.6% vs. 8%, p = 0.33). Patients with Lemmel's
      syndrome were significantly older (mean 74.5 years vs. 66.6 years, p < 0.001) and
      had significantly larger diverticula (mean 3.9cm vs. 1.9cm, p < 0.001). Of these
      39 patients, 15 received endoscopic sphincterotomy (38.5%), 3 received stenting
      (7.7%), 6 had impacted bezoars (15.4%), 2 underwent surgery due to failed
      cannulation (5.1%), 19 (48.7%) received conservative treatment after diagnostic
      cholangiography, and 1 had significant bleeding (2.6%). CONCLUSIONS: Patients
      with Lemmel's syndrome are older and have larger juxtapapillary duodenal
      diverticula. Endoscopic cannulation is not hampered by this anatomical difference
      and is not associated with higher complication rate.

PMID- 16995450
TI  - Lugol staining and histological evaluation of esophageal mucosa in achalasia.
AB  - BACKGROUND/AIMS: Esophageal cancer in achalasia is often diagnosed in the
      advanced stage, which makes for a poor prognosis. Therefore, the aim of this
      study was to evaluate the macroscopic and histological features of the esophageal
      mucosa in order to improve the early detection of cancer. METHODOLOGY: We studied
      the macroscopic features of esophageal mucosa using Lugol's solution and compared
      them with histological analysis of the entire mucosa in 20 esophagectomy
      specimens resected for achalasia. Intraepithelial neoplasia, when detected, was
      selected for DNA ploidy analysis through static cytometry. RESULTS:
      Macroscopically, the mucosa showed opacification and/or diffuse irregularities in
      19 specimens. Advanced squamous cell carcinoma was diagnosed in 2 cases. Using
      Lugol, the esophageal mucosa acquired irregular brownish color. Clear unstained
      areas were circumscribed in 5 esophagi. They were macroscopically defined as
      ulcer, neoplasia (2 cases) and mucosal irregularities (2 cases). The histological
      analysis showed ulcer, squamous cell carcinoma (2 cases), Barrett's esophagus and
      esophagitis, respectively. The histological study of the stained mucosa revealed
      minute foci of DNA aneuploid intraepithelial neoplasia in 4 cases. CONCLUSIONS:
      Macroscopic examination using Lugol failed to identify minute foci of early
      carcinoma. The stained mucosa does not exclude the esophageal cancer risk in
      achalasia.

PMID- 16995451
TI  - Expression of mucin-2 and correlation with PAS-alcian blue stain in Barrett's
      esophagus.
AB  - BACKGROUND/AIMS: Hematoxylin-eosin stain may fail to show intestinal metaplasia
      in Barrett's esophagus, and PAS-alcian blue may present difficulties of
      interpretation due to its more heterogeneous staining. We investigated whether
      Mucin-2 is a good substitute for PAS-alcian blue in the detection of goblet
      cells. METHODOLOGY: Biopsy specimens from 47 Barrett's esophagus patients were
      stained with hematoxylineosin and PAS-alcian blue. Mucin-2 expression was
      evaluated with monoclonal antibody. The intra- and interobserver agreements about
      the expression of Mucin-2 and PAS-alcian blue stain were determined by kappa
      statistics. RESULTS: PAS-alcian blue and Mucin-2 were positive in all cases.
      Mucin expression was positive in goblet cells and few columnar cells. PAS-alcian
      blue showed heterogeneous staining. The columnar epithelium and the submucosal
      glands were also stained. Intra- and interobserver agreement in the
      identification of intestinal metaplasia was 100%. CONCLUSIONS: Mucin-2 agreed
      fully with PAS-alcian blue. The intra- and interobserver agreement was perfect,
      justifying its use in the diagnosis of Barrett's esophagus.

PMID- 16995452
TI  - Evaluation of inferior right hepatic vein-preserving hepatectomy with resection
      of the superior right hepatic vein.
AB  - BACKGROUND/AIMS: If the superior right hepatic vein (SRHV) is resected, segment 6
      will be drained by the inferior right hepatic vein (IRHV) and congestion will not
      occur. However, early postoperative liver function and long-term regeneration of
      segment 6 after IRHV-preserving hepatectomy remains unclear. METHODOLOGY: Three
      patients undergoing IRHV-preserving hepatectomy were examined. One (case 1) had
      liver metastasis from sigmoid colon cancer and two (cases 2 and 3) had
      hepatocellular carcinoma. Resection of segments 7 and 8 along with the SRHV was
      performed in cases 1 and 2. Anterior sectionectomy and resection of segment 4a
      along with the SRHV and middle hepatic vein (MHV) was performed in case 3. The
      volume of each sector was calculated by summation of each CT area. RESULTS: The
      warm ischemic time of the three cases was 50-78 min, operative blood loss was 496
      914 g, and operating time was 4-7 h. There was no significant change in diameter
      of the IRHV and MHV before and after surgery. Intraoperative color Doppler
      ultrasonography was a useful technique for evaluating intrahepatic venous
      communication. Part of segment 6 had previously been resected in case 1, and at
      outpatient follow-up this segment was found to have become atrophic. In cases 2
      and 3, the remnant posterior sector became hypertrophic. CONCLUSIONS: IRHV
      preserving hepatectomy can retain a greater proportion of liver parenchyma than
      right hepatectomy. Postoperative liver function was well maintained in our
      patients and there were no serious complications. Long-term follow-up showed
      hypertrophy of the remnant posterior sector except in one case. To minimize
      surgical damage, for example in patients with poor liver function or preoperative
      complications, IRHV-preserving hepatectomy should be considered.

PMID- 16995453
TI  - Four-dimensional ultrasonography for therapeutic radiofrequency ablation for
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: We examined whether four-dimensional real-time flow imaging on
      ultrasonography (US) is valuable to display the accurate position of percutaneous
      radiofrequency ablation (RFA) needle in the nodule of hepatocellular carcinoma
      (HCC). METHODOLOGY: Ten patients with 12 HCC nodules were studied; nine were
      infected with hepatitis C virus (HCV) and one was diagnosed as non-B non-C.
      Diagnosis was done by helical dynamic CT and/or celiac angiography. Tumor
      vascularities in the early arterial and post-vascular phases after injection of a
      microbubble contrast agent were assessed by real-time US scanning of coded
      harmonic imaging and intermittent interval-delay scanning with a wide-band power
      Doppler technology. Percutaneous RFA was performed with four-dimensional real
      time flow imaging under US to display the accurate position of cool-tip needle.
      RESULTS: It was possible to obtain accurate position of the needle during RFA
      procedure in all 12 nodules. The needle was confirmed to be inserted into the
      center of the tumor nodule by various angles. The simultaneous study before RFA
      therapy showed the inflow of arterial blood and tumor staining in all nodules at
      early arterial phase of coded harmonic angio on contrast-enhanced US scan.
      Posttreatment study to evaluate the therapeutic efficacy showed no blood flow at
      both early vascular and post-vascular phases. No residual blood flow was noted on
      early phase of CT scan with adequate safety margin. There was no discrepancy in
      the finding at early phase between contrast-enhanced US and dynamic CT.
      CONCLUSIONS: It appeared that four-dimensional real-time US provided more
      perceptible information on the spatial relationship between RFA needle and the
      target lesion, and resulted in accurate therapeutic efficacy for percutaneous RFA
      procedure.

PMID- 16995454
TI  - Immunoscintigraphy of colorectal carcinomas with radiolabeled monoclonal antibody
      fragments.
AB  - BACKGROUND/AIMS: The aim was evaluation of the accuracy and clinical impact of
      the immunoscintigraphy for the detection of metastases and recurrences of
      colorectal carcinomas using two different radiolabeled antibody fragments.
      METHODOLOGY: The study was performed in 5 patients with IMACIS 1 containing the
      cocktail of 111MBq 131I MoAb 19-9 F(ab')2 and MoAb anti-CEA F(ab')2 and 8
      patients with INDIMACIS 19-9 containing 150MBq of 111In-labeled MoAb 19-9
      F(ab')2. RESULTS: With IMACIS 1, in all the patients, both tumor marker values
      were elevated. The number of TN was 3/5 and TP 2/5. From 2 TP, one had recurrence
      of the diseases with peritoneal carcinosis and one with liver metastases. In one
      patient, the results influenced the therapeutical management. With INDIMACIS 19
      9, there were 2/8 TN, with borderline value of CEA and CA 19-9. TP were 6/8 (all
      with elevated tumor marker values, five of them many times; 3 with recurrences, 1
      with recurrence and liver metastases and two with only liver metastases. In three
      patients, immunoscintigraphy influenced patient management. CONCLUSIONS: With
      both radiopharmaceuticals, immunoscintigraphy significantly influenced the
      patient management or it was complementary. It would be performed in the
      detection of recurrence, assessment of viability and follow-up of the therapy.

PMID- 16995455
TI  - Surgical outcomes of laparoscopic vs. open surgery for rectal carcinoma--a
      matched case-control study.
AB  - BACKGROUND/AIMS: The present study evaluated the short- and middle-term surgical
      outcomes of laparoscopic surgery (LS) for rectal carcinoma in comparison with a
      case-control series of open surgery (OS). METHODOLOGY: Between February 1998 and
      December 2004, 47 patients with rectal carcinoma underwent LS. These patients
      were compared with a conventional OS group matched for age, gender, location of
      tumor, surgical procedure, extent of resection and pathological stage. RESULTS:
      The median follow-up period for the LS group and the OS group was 25 and 49
      months, respectively. In the LS group, median operative time was significantly
      longer but median blood loss was lower than those in the OS group. There was one
      requiring conversion to OS. Postoperative intervals until liquid and solid
      intakes, and hospital stay were significantly shorter in the LS group.
      Postoperative complications rates are similar and anastomotic leakage occurred in
      one patient in each group. In the LS group, the levels of white blood cell count
      on postoperative day 1 and C-reactive protein on postoperative days 1 and 2 were
      significantly lower than those in the OS group. CONCLUSIONS: LS for rectal
      carcinoma provides benefits during the early postoperative period without
      increase in morbidity or mortality.

PMID- 16995456
TI  - Esophageal perforation--associated risk with balloon tamponade after endoscopic
      therapy. Myth or reality?
AB  - BACKGROUND/AIMS: Variceal bleeding is still associated with high mortality and
      balloon tamponade may be a lifesaving measure when endoscopic therapy is not
      available or feasible. The risk of esophageal perforation with balloon tamponade
      after endoscopic therapy is still uncertain. The aims of the study were to
      investigate balloon tamponade effectiveness and safety after endoscopic therapy.
      METHODOLOGY: Retrospective analysis of 100 consecutive episodes of acute variceal
      bleeding treated with the Sengstaken-Blakemore tube. RESULTS: Balloon tamponade
      had an overall effectiveness of 61%. The Child-Pugh score was significantly
      higher in patients who failed balloon tamponade. In 48 cases balloon tamponade
      was preceded by failure of endoscopic therapy. Balloon tamponade was more
      effective if a previous attempt to perform endoscopic therapy happened (75% vs.
      48%; p = 0.006). Aspiration was the most frequent complication. No cases of
      esophageal perforation were registered. CONCLUSIONS: Currently balloon tamponade
      is only used as a temporary bridge to other strategies, when other forms of
      hemostatic therapies do not succeed. Balloon tamponade was more effective in
      patients with less severe hepatic dysfunction. Previous attempts to perform
      endoscopic therapy may augment tamponade effectiveness without increasing the
      risk of esophageal perforation.

PMID- 16995457
TI  - Prospective assessment of the role of antibiotic prophylaxis in ERCP.
AB  - BACKGROUND/AIMS: Despite the existence of published recommendations, various
      studies of antibiotic prophylaxis have reached conflicting conclusions, and
      controversy exists regarding the role of antibiotic prophylaxis in ERCP. The aim
      of this study was to analyze the efficacy of the intramuscular administration of
      clindamicine and gentamicine before ERCP. METHODOLOGY: Sixty-one consecutive
      patients referred for ERCP were prospectively randomized to receive either
      clindamicine 600mg and gentamicine 80mg, both intramuscularly one hour before the
      ERCP (group I; 31 patients) or not (group II; 30 patients). Two blood samples
      were obtained from every patient (just before endoscopy and within 5 minutes of
      withdrawal of the endoscope) and were incubated for 7 days and examined daily for
      growth of bacteria. Patients were closely monitored for 7 days after endoscopy to
      detect the development of infectious complications. RESULTS: Only 7 cultures from
      7 patients were positive. Four were obtained post-ERCP (two patients in group I
      and two in group II) and the remaining three before endoscopy. The post-ERCP
      isolated bacteria were: Streptococcus mitis, Peptoestreptococcus anaerobious,
      Moraxella spp and Escherichia coli. Two patients, one from each group, developed
      post-ERCP cholangitis that were solved with medical treatment. CONCLUSIONS: Our
      findings indicate that ERCP induce bacteremia in a small group of patients and
      suggest that prophylactic administration of clindamicine plus gentamicine does
      not reduce the incidence of bacteremia and cholangitis, and do not support the
      routine use of prophylactic antibiotics prior to ERCP.

PMID- 16995458
TI  - Taylor's method: a therapeutic alternative for perforated gastroduodenal ulcer.
AB  - BACKGROUND/AIMS: In the context of actual trends towards an efficient and less
      aggressive therapy of peptic ulcer, it seems that Taylor's method, in selected
      cases of perforated gastroduodenal ulcers (PGDU), comes again into attention. The
      aim of this study was to present our 16 years' experience with Taylor's treatment
      as an efficient option for sealed perforated ulcers, and to highlight the
      indications and advantages of this method. METHODOLOGY: A retrospective study,
      and prospective since 1990, was carried out on a series of 64 patients out of 592
      (10%) diagnosed with PGDU between 1987 and 2003. The patients were carefully
      evaluated, particularly looking for clinical, laboratory and imaging diagnosis
      factors, indicating potential candidates for conservative approach: short
      history, hydropneumoperitoneum in small amount on admission. Two thirds of the
      patients presented in the Emergency Unit less than 12 hours from the onset of the
      symptoms. The diagnosis of PGDU was established by corroborating the obvious
      symptoms and abdominal signs with erect chest X-ray and ultrasonography (US) of
      the abdomen. The efficiency of Taylor's method, consisting of nasogastric
      aspiration, fluids resuscitation, parenteral broad spectrum antibiotics and
      antisecretory drugs, was assessed by meticulous repeated physical examinations,
      dynamics of WBC (white blood cell) and US. In case of failure, this method
      remained as a part of preoperative treatment. RESULTS: The method was successful
      in 57 out of 64 (89%) cases of perforated peptic ulcer disease, selected from the
      592 cases admitted with perforated peptic ulcer following the clinical and
      imaging criteria previously mentioned. The presence of pneumoperitoneum certifies
      the diagnosis of PGDU, but the amount of peritoneal fluid assessed by US predicts
      the success of the procedure. Seven patients developed complications (10.9%),
      mainly intraabdominal abscesses and only four of them needed surgical drainage.
      The mortality was nil. After discharge all patients were referred to
      gastroenterologists for monitoring the medical treatment and no recurrence was
      encountered. CONCLUSIONS: The Taylor's method is a reliable alternative in
      selected cases of perforated gastroduodenal ulcers, the main advantage being the
      avoidance of anesthetic and surgical stress with their potential morbidity and
      mortality.

PMID- 16995459
TI  - Ultrasonographic bisection approximation method for gastrointestinal obstruction
      in ER.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the accuracies of using
      ultrasonography in determining the levels and causes of gastrointestinal
      obstruction in the emergency department. METHODOLOGY: 229 patients who visited
      the emergency department with the clinical impression of gastrointestinal
      obstruction were studied. The gastrointestinal tract was systematically scanned
      from the anatomically fixed portions to movable portions in the peritoneum by
      "bisection approximation method". The obstructive levels and possible etiologies
      were investigated. The finding was correlated with final surgical or further
      radiological diagnosis. RESULTS: The sensitivity, specificity and accuracy of
      ultrasonography in determining the obstruction of gastrointestinal tract were
      97%, 87% and 93%. In 150 patients with diagnosis of gastrointestinal obstruction
      by ultrasonography, the accuracies of predicting obstructive levels in the
      gastric outlet and duodenum, the jejunum and ileum, and the colon were 100%, 74%,
      and 98% respectively. 67%, 36%, and 78% of obstructive etiologies could be
      correctly judged in these segments respectively. CONCLUSIONS: Ultrasonography is
      a useful tool in the localization of obstructive levels and the determination of
      etiologies of gastrointestinal obstruction in the emergency room. It can guide
      physicians to choose further appropriate confirmation studies.

PMID- 16995460
TI  - Primary prophylaxis of variceal bleeding in cirrhotics awaiting liver
      transplantation.
AB  - BACKGROUND/AIMS: To evaluate the efficacy and safety of prophylactic band
      ligation and propranolol versus propranolol alone for the primary prophylaxis of
      variceal bleeding in patients with high-risk esophageal varices listed for liver
      transplantation. METHODOLOGY: Out of 152 cirrhotic patients included on the
      waiting list between January 2001 and January 2003, high-risk esophageal varices
      were detected in 72. These patients were randomized to undergo combined therapy
      or propranolol monotherapy. The actuarial probabilities of bleeding from
      esophageal varices and bleeding-related death were calculated by Kaplan-Meier
      method and compared using the log-rank test. RESULTS: Variceal eradication was
      achieved in 33 patients (91.6%) in 2.5 +/- 1.4 ligation sessions. The mean daily
      dose of propranolol was 72 +/- 25mg in the propranolol group and 68 +/- 21 mg in
      the ligation group. Six percent of patients in the ligation group and 31% in the
      propranolol group had one episode of bleeding during the 18 months of follow-up
      (p = 0.03). The actuarial probabilities of bleeding-free survival after 18 months
      of follow-up, in the ligation and monotherapy groups were 96% and, respectively,
      69% (p = 0.04). CONCLUSIONS: Endoscopic band ligation associated with propranolol
      significantly reduces the occurrence of the first episode of variceal bleeding
      and improves bleeding-related survival in cirrhotics included on the waiting
      list.

PMID- 16995461
TI  - Evaluation of the therapeutic effect using MD-CT immediately after RFA for HCC.
AB  - BACKGROUND/AIMS: Radiofrequency ablation (RFA) is an effective modality for
      treatment of hepatocellular carcinoma (HCC), because it can induce large
      coagulation necrosis in a few sessions. The aim of this study is to evaluate
      whether we can assess the therapeutic effect of RFA immediately after RFA.
      METHODOLOGY: Twenty-one patients (25 nodules) with HCC undergoing RFA treatment
      were enrolled in this study. Fourteen patients were treated with combination
      therapy of lipiodol chemoembolization and RFA, while 7 patients were treated with
      RFA alone. Dynamic computed tomography (CT) using multidetector row helical CT
      (MD-CT) was performed before, immediately after and 1 week after RFA.
      Simultaneously, multiplanar reconstruction (MPR) images were also obtained for
      comparison. RESULTS: With or without chemoembolization, the size of coagulated
      necrosis was almost the same between the time immediately after and 1 week after
      RFA. The therapeutic effect was able to be evaluated by dynamic CT scans
      immediately after RFA in all patients. Moreover, MPR images facilitate the
      detailed evaluation of the therapeutic effect. CONCLUSIONS: Examination of
      dynamic CT using MD-CT immediately after RFA is useful to evaluate the
      therapeutic effect and may enable a shorter hospital stay.

PMID- 16995462
TI  - Impact of pegylated interferon alfa-2a and ribavirin on hepatic fibrosis in liver
      transplant patients with recurrent hepatitis C: an open-label series.
AB  - BACKGROUND/AIMS: Patients with recurrent hepatitis C are often treated with
      interferon-based therapy in an attempt to prevent cirrhosis requiring
      retransplantation. We describe our experience with 32 patients with recurrent
      HCV. METHODOLOGY: Patients were followed prospectively after starting pegylated
      interferon alfa-2a 180 microg per week and ribavirin 1000-1200mg per day. HCV
      ribonucleic acid (HCVRNA) was repeated at three months, end of treatment (EOT)
      and six months after EOT for patients HCVRNA negative at EOT. RESULTS: There were
      22 males and 10 females. 21 patients have completed treatment, six remain on
      therapy and five were intolerant. In an intention-to-treat analysis, sustained
      viral eradication occurred in 40.6% of patients. Fibrosis scores were worse in
      eight patients of whom six were sustained responders. Three of these patients
      developed decompensated liver disease. Two were successfully retransplanted and
      remain HCVRNA negative after a mean follow-up of 11 months. CONCLUSIONS:
      Pegylated interferon alpha-2a and ribavirin were well tolerated in this small
      series. Sustained HCV eradication occurred in at least 40.6% of patients but
      progressive fibrosis occurred in 75% of sustained responders. This suggests that
      mechanisms other than recurrent HCV may be responsible for cirrhosis in sustained
      responders who remain at risk of developing decompensated liver disease.

PMID- 16995463
TI  - Preoperative portal vein embolization for liver malignancies.
AB  - BACKGROUND/AIMS: To study effectiveness of preoperative portal vein embolization
      before extensive hepatic resection in patients with primary or secondary liver
      malignancies. METHODOLOGY: Between December 1997 and May 2003, right portal vein
      embolization was performed in 24 patients. The indication to the procedure was a
      small amount (< 30%) of the future remnant liver. Ultrasound-guided percutaneous
      transhepatic puncture of the portal vein and embolization of its right lobar
      branch with Lipiodol, ethanol, gelatin sponge and/or steel coils were used.
      RESULTS: There were no complications of the procedure. In 19-56 (mean, 30) days,
      CT or MRI showed significant increase of the future remnant liver volume from 25%
      to 35% of the whole liver; the mean increase was 40%. Laparotomy was performed in
      15 patients. Right, extended right hepatectomy, and repeated resection were
      performed in 7, 6, and 1 patient respectively, while one patient underwent only
      exploration because of tumor progression. Of 14 resected patients, 11 showed no
      postoperative liver failure. The latter was medically cured in two of three
      remaining patients, while one patient (future remnant liver < 30% even after the
      embolization) died from liver failure in 20 days after the surgery. Hepatic
      resection is planning in 4 of 9 non-operated patients. The 5 patients were not
      operated because of tumor progression. CONCLUSIONS: Right portal vein
      embolization is a safe and technically simple procedure that decreases the risk
      of postoperative hepatic failure after major liver resection.

PMID- 16995464
TI  - Bowel injury associated with liver surgery for hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Bowel injury associated liver surgery is rare but can be fatal
      if not adequately treated. The contribution of underlying liver disease and
      previous hepatectomy to bowel injury in hepatectomy for hepatocellular carcinoma
      is unknown. METHODOLOGY: Clinical records of 531 patients who underwent hepatic
      resection without combined resection of the biliary tract or intestine for
      hepatocellular carcinoma during 13 years were reviewed. Differences in incidence
      of bowel injury according to presence or absence of liver cirrhosis, technique of
      hepatectomy, and history of hepatectomy were investigated. Outcome after
      treatment also was reviewed. RESULTS: Bowel injury occurred in 5 patients (0.9%).
      Previous hepatectomy history was associated with an increased incidence of bowel
      injury [repeat hepatectomy, 3/91 (3.3%), and first hepatectomy, 2/440 (0.5%), p =
      0.038]. Injury was recognized intraoperatively in two patients and
      postoperatively in three. In the former two patients, the injured bowel was
      repaired immediately but a fistula still developed in one patient. One patient
      with a fistula eventually required temporary fecal diversion and eventually
      limited colectomy. The other three patients were treated by continuous external
      drainage, but two of them required debridement or colic sleeve resection.
      CONCLUSIONS: Previous hepatectomy increases the risk for bowel injury during
      hepatectomy. Care must be taken to prevent adhesion to the hepatic cut surface.
      Careful use of electrocautery to prevent burn injury also should be taken.

PMID- 16995465
TI  - The effects of occlusive techniques on the short-term prognosis after liver
      resections.
AB  - BACKGROUND/AIMS: Anatomic liver resection can be performed without vascular
      occlusion, but controlling blood loss during liver parenchyma dissection by
      compression or clamping of vessels in the liver hilus is almost the rule. The aim
      of this study is to assess the negative consequences of different types of
      occlusion techniques used during liver parenchyma dissection. METHODOLOGY: From
      2001 to 2003, 43 anatomical liver resections were performed in patients with
      primary and metastatic tumors. Patients were divided into three groups according
      to the duration and the type of occlusion of incoming blood vessels in the
      hepatoduodenal ligament (continuous over 20 min, continuous under 20 min, or
      interrupted blood-vessel occlusion for 5 min after every 20 min of occlusion).
      Blood level of bilirubin, ALT, AST and prothrombin time were evaluated in the
      postoperative period. RESULTS: Within the continuous occlusion group that lasted
      longer than 20 minutes (37 +/- 14 min) increase in levels of bilirubin and liver
      enzymes and decrease of prothrombin time were noted as compared to the group with
      occlusion shorter than 20 minutes and to the group with intermittent occlusion
      over 20 minutes (34 +/- 5 min). CONCLUSIONS: From results issued, it can be seen
      that using intermittent occlusion during liver parenchyma dissection lasting
      longer than 20 minutes causes less ischemic-reperfusion injury in the remaining
      liver parenchyma than by using continual occlusion.

PMID- 16995466
TI  - FK506 may reduce early liver injury following living related liver
      transplantation.
AB  - BACKGROUND/AIMS: We investigated the influence of FK506 which has been used
      frequently after transplant surgery as an immunosuppressant, on liver injury
      after partial hepatectomy by comparing laboratory data from donors and recipients
      after liver transplantation. METHODOLOGY: Seventeen donors and respective
      recipients who underwent living related donor liver transplantation were included
      in the present study. Serum levels of transaminases and cytokines were measured
      and compared preoperatively and in the early period after the operation. RESULTS:
      Serum level of asparaginic acid aminotransferase in the postoperative day 1 was
      significantly higher in the donor group. Serum levels of alanine aminotransferase
      in the early period after the operation were significantly higher in the donor
      group. Serum levels of interferon y and soluble Fas ligand in the early period
      after the operation were significantly higher in the donor group. Steroid doses
      administered were significantly higher in the recipient group. CONCLUSIONS: FK506
      administration and steroid administration in larger doses were thought to reduce
      serum transaminase levels of the recipient group. These findings might suggest
      that cell-mediated immunity weigh heavier than the operation time of ischemia
      reperfusion injury as a cause of liver injury after partial hepatectomy.

PMID- 16995467
TI  - TIPSS in the treatment of ectopic variceal bleeding.
AB  - BACKGROUND/AIMS: Bleeding from ectopic varices is a well recognized life
      threatening complication of portal hypertension but the optimal treatment of this
      problem is yet to be established. METHODOLOGY: We retrospectively reviewed
      patients with ectopic variceal bleeding who underwent transjugular intrahepatic
      portosystemic shunting for recurrent bleeding not responding to conservative
      management. RESULTS: Over an eleven-year period we identified ten patients who
      underwent TIPSS for ectopic variceal hemorrhage. Six patients bled from rectal
      varices and four from stomal varices. TIPSS was successful in nine patients. The
      Childs-Pugh grade of the patients was A=3, B=3 and C=4. The follow-up period
      ranged from 7 days to 1380 days. Rebleeding occurred in three patients, two of
      whom died. The remaining patient had a blocked TIPSS and successfully underwent
      repeat stenting which re-established patency. Four patients (Childs B=2, Childs
      C=2) died within 60 days. All three patients with Childs A liver disease were
      alive at one year. CONCLUSIONS: TIPSS can be used effectively to treat ectopic
      variceal bleeding. Patients with Childs grade A liver disease appear to do well
      with TIPSS. Those with advanced liver disease (Childs B & C) have a uniformly
      poor outcome. In these patients ectopic variceal hemorrhage is likely to
      represent a terminal event.

PMID- 16995468
TI  - Cost-utility of living donor liver transplantation in a single Japanese center.
AB  - BACKGROUND/AIMS: Living donor liver transplantation is becoming increasingly
      important in the Western world, but the economic issues remain controversial. We
      conducted a cost-utility analysis to evaluate whether living donor liver
      transplantation is cost-effective. METHODOLOGY: Cost and utility analyses were
      performed in a longitudinal survey of a single center in Sapporo, Japan. Medical
      costs were derived from 11 patients who underwent living donor liver
      transplantation. Health utility was measured in quality-adjusted life year. Data
      for health utility scores were derived from 19 patients who underwent living
      donor liver transplantation. RESULTS: Median medical cost was U.S. dollars
      154,626 from the first day of preoperative evaluation to 24 months post
      transplantation. Cumulative quality-adjusted life years were 1.60 at 24 months
      after transplantation. Medical cost per quality-adjusted life year decreased
      progressively, leading to medical cost of U.S. dollars 605,131 per quality
      adjusted life year at 3 months to U.S. dollars 94,169 at 24 months after
      transplantation. The results were sensitive to medical cost. CONCLUSIONS: Follow
      up survey identified progressive increases in the cost-effectiveness of living
      donor liver transplantation for patients with end-stage liver disease. Living
      donor liver transplantation appears to represent a cost-effective medical
      technology.

PMID- 16995469
TI  - Outcome and pattern of recurrence after curative resection for hepatocellular
      carcinoma in patients with a normal liver compared to patients with a diseased
      liver.
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate whether differences
      existed in demography and outcome after resection for hepatocellular carcinoma
      (HCC) in patients with a normal liver compared to patients with a diseased liver.
      METHODOLOGY: Twenty-seven Caucasian patients with HCC in a histologically proven
      normal liver (NL group) in the Netherlands and 141 Asian patients with HCC in a
      diseased liver (DL group) in Japan underwent a curative liver resection. Patient
      and tumor characteristics, post-resectional disease-free, overall survival rates
      and pattern of recurrence were investigated. RESULTS: HCC's in the NL group were
      found to be larger, in a more advanced stage and needed more extended resections
      compared to HCC's in the DL group. Microvascular invasion was similar in both
      groups, while capsule formation was observed less in the NL group. Overall
      survival and disease-free survival after curative resection were not
      statistically different between both groups. Also even after stratification for T
      stage, there was no difference in survival. Although the rate of recurrence was
      similar in both groups, a significantly higher number of extrahepatic metastases
      was observed in the NL group. CONCLUSIONS: Distinct demographic differences
      existed between patients with HCC in the NL group compared to patients in the DL
      group. Extrahepatic recurrences were more frequent after curative resection for
      HCC in a normal liver. No difference in survival was demonstrated between both
      groups.

PMID- 16995470
TI  - Effects of dual inhibitor of cyclooxygenase and 5-lipoxygenase on acute
      necrotizing pancreatitis in rats.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate the influence of dual
      inhibitor of cyclooxygenase and 5-lipoxygenase (ER-34122) on acute necrotizing
      pancreatitis (ANP) induced by glycodeoxycholic acid in rats. METHODOLOGY: ANP was
      induced in 96 rats by standardized intraductal glycodeoxycholic acid infusion and
      intravenous cerulein infusion. Rats were divided into six groups (6 rats in each
      group): Sham + saline, sham + ER-34122, which was dissolved in
      hydroxypropylmetylcellulose (TC-5RW), sham + TC-5RW, ANP + saline, ANP + ER-34122
      and ANP + TC-5RW. Six hours after ANP induction ER-34122 (30 mg/kg), saline or TC
      5RW was given by feeding tube. At the 12th hour, routine cardio-respirator, renal
      parameters were monitored to assess organ function. Serum amylase, alanine amino
      transferase (ALT), interleukin 6 (IL-6), lactate dehydrogenase (LDH) in
      bronchoalveolar lavage (BAL) fluid, serum concentration of urea, tissue activity
      of myeloperoxidase (MPO) and malondialdehyde (MDA) in pancreas and lung were
      measured. Pancreas histology was examined. In the second part of the study 60
      rats were studied in four groups similar to first part. Survival of all rats was
      monitored for 24 hours. RESULTS: The induction of ANP resulted in significant
      increase in mortality rate, pancreatic necrosis and serum activity of amylase,
      ALT, IL-6, LDH in BAL fluid, serum concentration of urea, tissue activity of MPO
      and MDA in pancreas and lung, and significant decrease of serum concentrations of
      calcium, blood pressure, urine output and pO2. NAC did not change serum activity
      of amylase. The use of ER-34122 inhibited the changes in blood pressure, pO2,
      serum activity of ALT, pancreatic MPO and MDA levels, partially urine output, LDH
      level in BAL fluid and pancreatic damage. But ER-34122 could not effect the
      changes, such as serum activity of amylase, IL-6, serum concentration of urea and
      calcium, MPO and MDA levels in lung and the mortality rate. CONCLUSIONS: The use
      of ER-34122 has a limited value on the course of ANP. It has no role in the
      treatment of ANP.

PMID- 16995471
TI  - Alternative treatment modalities of infected pancreatic necrosis.
AB  - BACKGROUND/AIMS: Infected pancreatic necrosis diagnosed by fine needle aspiration
      (FNA) is generally considered an indication for surgery. Percutaneous drainage
      can postpone surgical intervention and in some cases can even have a therapeutic
      effect. Furthermore, targeted antibiotic therapy alone, based on bacterial
      cultures from FNA, can result in a full recovery. A retrospective analysis was
      carried out on the various treatment modalities of infected pancreatic necrosis.
      METHODOLOGY: Eighty patients with infected pancreatic necrosis were treated in
      the Department of Surgery, Teaching County Hospital, Gyor, Hungary between 1998
      and 2003. Seventy-four patients required surgical intervention, 12 of which
      underwent prior ultrasound or CT-guided drainage. RESULTS: In patients with
      previous percutaneous drainage the average time to first surgical intervention
      was 30 days (n=12). However, in those patients who did not undergo percutaneous
      drainage the time to initial surgical intervention was 15.6 days. This was
      statistically significant (p = 0.001). There was a full recovery in 3 out of the
      15 patients, who underwent percutaneous drainage. This figure of 20% corresponds
      with that in the published literature. Three of the total 80 patients studied
      made a complete recovery when treated with targeted antibiotic therapy alone and
      did not require further radiological or surgical intervention. CONCLUSIONS: Our
      data indicate that percutaneous drainage can postpone surgical intervention.
      Furthermore, we demonstrate that percutaneous drainage alone can lead to full
      recovery in selected cases. In addition, targeted antibiotic therapy based on FNA
      may result in the complete recovery of a stable patient without requiring
      radiological or surgical intervention.

PMID- 16995472
TI  - Comparative evaluation of p53 mutation in pancreatic adenocarcinoma and chronic
      pancreatitis.
AB  - BACKGROUND/AIMS: Pancreatic adenocarcinoma (PA) has a very poor prognosis. In
      patients suffering from chronic pancreatitis (CP) the risk for the PA development
      is higher than in the general population. The purpose of the study was to compare
      the prevalence of p53 mutations in PA and CP in order to evaluate their
      usefulness in differential diagnosis of those diseases. METHODOLOGY: We examined
      49 patients who underwent Whipple resection or distal pancreatectomy for
      pancreatic adenocarcinoma (26 subjects) or chronic pancreatitis (23 subjects).
      DNA from pancreatic tissue was analyzed for p53 mutations with PCR/SSCP methods.
      RESULTS: The p53 gene mutation has been shown in 16 (61.5%) of the PA patients (9
      in exon 5 and 7 in exon 7) and in 2 (8.6%) of CP patients (1 in exon 5 and 1 in
      exon 8; p < 0.001). There was a significant correlation between p53 mutation and
      G3 tumor differentiation (p < 0.01). Overall median survival in patients with PA
      was 8.5 months. No relationship between presence of p53 mutation and survival
      time in PA patients has been observed. CONCLUSIONS: The specificity of p53
      mutation for pancreatic cancer is very high. Our results indicate that p53 gene
      mutation may provide an additional tool in differential diagnosis of CP and PC.

PMID- 16995474
TI  - Serum endostatin levels in gastric cancer patients: correlation with
      clinicopathological parameters.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the predictive role of the
      circulating levels of endostatin in gastric cancer patients. METHODOLOGY: This
      study is a retrospective case-control study. We measured serum endostatin levels
      of 30 patients aged between 34-83 years with gastric cancer and 30 patients
      without malignant pathology operated for benign pathologies with age ranging from
      18 to 69. RESULTS: Serum levels of endostatin were correlated with the Lauren
      classification. Significantly higher serum endostatin levels were obtained in
      Lauren intestinal type tumors than Lauren diffuse type tumors. CONCLUSIONS: These
      data suggest that serum endostatin levels do not correlate with
      clinicopathological parameters, except tumor histopathology (according to Lauren
      classification), in gastric cancer patients.

PMID- 16995473
TI  - P53 and MIB-1 expression in gastrointestinal stromal tumor (GIST) of the stomach.
AB  - BACKGROUND/AIMS: Routine clinical approaches for evaluating the risk of
      recurrence in patients with gastrointestinal stromal tumor (GIST) of the stomach
      have been limited. Some biomolecular markers may yield more useful information in
      identifying patients having a higher risk of recurrence. In the current
      retrospective study, we selected MIB-1 and p53 expression as markers to detect at
      risk patients. METHODOLOGY: We enrolled 31 gastric GIST patients who underwent
      gastrectomy at Kagoshima University Hospital. Patients were classified into two
      groups based on mitosis and tumor diameter. p53 and MIB-1 expression in the
      primary tumor were detected immunohistochemically. RESULTS: The patients were
      classified as having a malignant GIST (20 cases), a benign GIST (11 cases). MIB-1
      labeling index (LI) varied from 1 to 32% (average 7.8%). The MIB-1 LI for
      malignant GISTs was 6.3 +/- 6.4%, which was significantly higher than the 3.2 +/-
      2.5% observed for benign GISTs (p < 0.01). The 3 patients positive for p53 died
      as a result of GIST recurrence. CONCLUSIONS: In addition to routine pathological
      evaluation, expression of p53 and MIB-1 may provide more accurate information
      regarding the risk of GIST recurrence. Especially, p53 expression of the tumor
      may indicate patients having a high risk of recurrence.

PMID- 16995475
TI  - Helicobacter pylori infection, but not mucosal atrophy, significantly affects
      serum pepsinogen level after gastric cancer surgery.
AB  - BACKGROUND/AIMS: Helicobacter pylori (Hp) infection is frequently observed in the
      remnant stomach after gastric cancer surgery, and is considered to play one of
      the important roles in chronic mucosal inflammation and cancer development.
      METHODOLOGY: Serum pepsinogen (PG) levels were measured in one hundred and eight
      patients after gastrectomy performed because of gastric cancer. The correlation
      between PG levels and the grade of mucosal inflammation in the remnant stomach
      was investigated together with the status of Hp infection. RESULTS: No
      statistical difference in serum PG level was found according to the severity of
      reflux gastritis, or grade of mucosal atrophy. Significantly higher serum PG II
      level and lower PG I/II ratio were found in cases with histologically severe
      mucosal inflammation than in those without inflammation. In Hp positive cases, PG
      I level stayed constant while PG II level scored a significantly higher value
      than those of negative cases. As a result, PG I/II ratio became significantly
      lower in cases with Hp infection than in those without infection. CONCLUSIONS: Hp
      infection and active mucosal inflammation, but not bile reflux or mucosal
      atrophy, significantly affect on the serum PG level in patients with remnant
      stomach after gastric cancer surgery. Serum PG level was suggested to indicate
      the grade of acute and chronic Hp-related inflammation in those patients.

PMID- 16995477
TI  - Paraaortic lymph node dissection for gastric cancer in 244 consecutive cases.
AB  - BACKGROUND/AIMS: More than 20% of patients with advanced gastric cancer show
      paraaortic lymph node metastasis. However, whether extensive paraaortic
      lymphadenectomy is beneficial remains controversial. We performed a prospective
      study of paraaortic lymphadenectomy for patients with advanced gastric cancer.
      METHODOLOGY: From January 1991 to March 2004, 244 consecutive patients with
      advanced gastric cancer underwent gastrectomy with paraaortic lymphadenectomy
      with curative intent. The patients were divided into 3 groups according to the
      period: Group 1 (1991-1995), Group 2 (1996-1999), and Group 3 (2000-2004).
      RESULTS: Overall mortality rate was 2.4%, and it fell rapidly from 7.1% in Group
      1 to 0% in Group 3. Postoperative complications occurred in 35.6%. High age and
      postoperative complications were significant predictive factors for operative
      death. Preoperative comorbidity, positive distal margin, and pancreatectomy were
      significant predictive factors of postoperative complications. Depth of cancer
      invasion was correlated with paraaortic node metastasis. Ten patients with
      paraaortic node metastases survived for more than 5 years. Operative curability
      and postoperative complications were significant prognostic factors for patients
      who underwent this procedure. CONCLUSIONS: Paraaortic lymph node dissection for
      gastric cancer should be performed in patients with tumors deeper than the
      serosa. Pancreatectomy should be avoided, with careful management required in
      cases of unavoidable pancreatectomy.

PMID- 16995476
TI  - Influence of aging, gastric mucosal atrophy and dietary habits on gastric
      secretion.
AB  - BACKGROUND/AIMS: Studies in Japan have reported on the association between
      gastric secretion and age with consideration given to gastric mucosal atrophy but
      not pepsin secretion. Though recent reports have shown enhanced gastric secretion
      in the Japanese, attributed to dietary westernization, the association between
      diet and gastric secretion is not clear. In this study, the association between
      gastric secretion and mucosal atrophy, age, and dietary habits was evaluated.
      METHODOLOGY: The subjects were 47 preoperative patients without upper
      gastrointestinal disorders. Acid secretion, pepsin secretion, serum pepsinogen
      level, and serum Helicobacter pylori antibody titer were measured. Dietary habits
      were investigated by questionnaire. RESULTS: Gastric secretion did not differ
      among the young, middle, and elderly age groups. Compared with the group without
      atrophy (pepsinogen I/II > 3.0, 32 subjects), the group with atrophy (I/II < or =
      2.5, 11 subjects) showed significantly decreased gastric secretion and a
      significantly high Helicobacter pyloriseropositive rate. In the group without
      atrophy, acid and pepsin secretion was significantly correlated with energy
      intake, pepsin secretion was significantly correlated with glucose intake, and
      gastric secretion tended to increase with age. CONCLUSIONS: In the absence of
      gastric mucosal atrophy, gastric secretion does not decrease with age, and is
      related to dietary habits.

PMID- 16995478
TI  - Preoperative IL-2 immunotherapy enhances tumor infiltrating lymphocytes (TILs) in
      gastric cancer patients.
AB  - BACKGROUND/AIMS: Tumor infiltrating lymphocytes (TILs), recognized as a tumor
      host reaction, have been linked to prognosis in various tumors, with a clear
      positive correlation between the density of the lymphoid infiltrate at the
      advancing margin of the tumor and the prognosis of the patients. TILs are
      somewhat activated by tumor associated antigens and by IL-2 endogenous release.
      The aim of this study is to verify if subcutaneously administered IL-2 is able to
      enhance TILs in gastric cancer patients and is able to influence the prognosis of
      the patients. METHODOLOGY: We enrolled 39 consecutive patients with gastric
      adenocarcinoma. Patients were randomized to be treated with surgery alone
      (control group, 20 patients) or with surgery plus preoperative IL-2 (Interleukin
      2) administration (treated group, 19 patients). Total lymphocytes, CD4 and
      CD4/CD8 were evaluated pre- and postoperatively. Peritumoral stromal reaction,
      neutrophils, lymphocytes and eosinophils infiltration in tumor histology were
      evaluated as well as survival curves and compared between the groups. RESULTS: IL
      2 treatment was safe and well tolerated, and in the IL-2 treated group a
      significant increase over the baseline pretreatment values of the total
      lymphocyte, CD4 and CD4/CD8 on both the 14th and 50th postoperative days was
      observed (p < 0.05). Peritumoral stromal reaction, neutrophils and eosinophils
      infiltration did not shown any statistical difference between the two groups.
      Otherwise we observed a statistically significant difference in the peri- and
      intratumoral lymphocytes infiltration between IL-2 treated and control patients
      (p = 0.000026). Median overall and disease-free survivals were longer, even if
      not significantly, in the IL-2 group than in the control arm (p = 0.089 and p =
      0.09 respectively). CONCLUSIONS: Our data shows that IL-2 seems to be able to
      induce substantial changes in the inflammatory infiltration of the neoplasm,
      improving the host activity toward the tumor and enhancing the TILs phenomenon in
      gastric cancer patients. This feature seems to improve the prognosis of the
      patients.

PMID- 16995479
TI  - Key factors for successful en bloc endoscopic submucosal dissection of early
      stage gastric cancer using an insulation-tipped diathermic knife.
AB  - BACKGROUND/AIMS: En bloc endoscopic mucosal resection (EMR) is presently
      considered to be the treatment of choice for endoscopically resectable early
      stage gastric cancer (EGC). Although a new EMR technique using an insulation
      tipped diathermic knife (endoscopic submucosal dissection using an IT knife: IT
      knife-ESD) is reportedly suitable for en bloc resection, a failure in en bloc
      resection (piecemeal resection) can occur. We retrospectively analyzed factors
      affecting the success rate of en bloc resection by IT knife-ESD. METHODOLOGY: A
      total of 71 gastric lesions were treated by IT knife-ESD. En bloc/piecemeal
      resection rates were investigated. Twelve potential factors associated with
      clinicopathological characteristics or procedures were analyzed univariately and
      multivariately. RESULTS: IT knife-ESD was successfully performed in all 71
      lesions. En bloc resection was achieved in 63 lesions (91%), while eight lesions
      (9%) were removed as two or more fragments (piecemeal resection). The
      multivariate analysis identified only one independent factor affecting the
      success rate of en bloc resection: the second-half period of procedure
      application. The en bloc resection rate was not associated with the tumor
      location/site, tumor size, specimen size, and ulceration within the tumor.
      CONCLUSIONS: Much experience with IT knife-ESD may resolve the tumor-related
      technical difficulties. It is true for this advanced procedure that endoscopist
      experience is highly likely to be a critical factor for treatment success. We
      consider that IT knife-ESD for EGC is feasible and safe when performed by
      experienced endoscopists.

PMID- 16995480
TI  - Factors affecting long-term clinical outcomes of endoscopic mucosal resection of
      early gastric cancer.
AB  - BACKGROUND/AIMS: Endoscopic mucosal resection (EMR) has been widely accepted as a
      treatment option for early gastric cancer (EGC) in selected cases. The purposes
      of this study were to evaluate the long-term outcomes and the factors affecting
      the clinical outcomes, of EMR performed in EGC. METHODOLOGY: Between April 1996
      and March 2005, 147 patients have undergone EMR to treat EGC at Yonsei University
      Medical Center, Seoul, Korea. We assessed the clinical outcomes of the EMR for
      EGC in a long-term follow-up period. We also reviewed the medical records of the
      patients including demographic data, endoscopic characteristics of the lesion and
      histopathologic findings. RESULTS: The histopathologic evaluations after the EMR
      treatment showed that overall complete resection rate was 84.6% (126/149) while
      complete resec tion rate of 93.5% was achieved in mucosal cancers (115/123). The
      success of complete resection was significantly affected by endoscopic gross type
      (depressed lesion), the degree of differentiation, and the depth of invasion,
      independently. There were only 5 cases of local recurrence during the follow-up
      periods, and the recurred or incompletely resected lesions were successfully
      treated by salvage operation or endoscopic retreatment. There was no disease
      related or treatment-related mortality during the follow-up period. CONCLUSIONS:
      EMR is a good and safe curative treatment option with feasible clinical outcomes
      in patients with EGC. It must be emphasized that a proper selection of candidates
      is mandatory to improve the clinical outcome of EMR in EGC.

PMID- 16995481
TI  - Laparoscopy-assisted total gastrectomy for a case of MALT lymphoma: a case
      report.
AB  - A case of laparoscopy-assisted total gastrectomy with regional lymph node
      dissection for MALT (mucosa-associated lymphoid tissue) lymphoma is reported. The
      patient was a 45-year-old male with MALT lymphoma. Eradication of Helicobacter
      pylori as the initial therapy had failed to halt progression of the tumor.
      Considering certainty of the second therapy, he was transferred to surgical
      treatment. Total gastrectomy was required and this was performed by the
      laparoscopy-assisted approach. The postoperative course was satisfactory and the
      patient has been disease-free for 5 years after the operation. Laparoscopic
      operation could be a useful option in the second-line treatment for MALT lymphoma
      after failure to eradicate H. pylori.

PMID- 16995482
TI  - Reflections on ethics as a part of the higher education curriculum.

PMID- 16995483
TI  - Creating an effective pedagogy for moral education.

PMID- 16995484
TI  - Can we ethically grade medical students?

PMID- 16995485
TI  - Physician socialization and the loss of idealism.

PMID- 16995486
TI  - Interprofessional education in health care.

PMID- 16995487
TI  - From principles to public health programs through uncertainty.

PMID- 16995488
TI  - Looking for ethics in all the right places.

PMID- 16995489
TI  - The primary obligation of physicians should be to their patients, not to society.

PMID- 16995490
TI  - Portraits of my mother.

PMID- 16995491
TI  - Madagascar.

PMID- 16995492
TI  - Suppression of interferon-related promoter activation by hepatitis C virus
      proteins expressed in cultured cells.
AB  - Interferon is important for anti-viral defense of the host. The E2, NS3/4A, and
      NS5A proteins of hepatitis C virus (HCV) have recently been reported to confront
      anti-viral action induced by interferon. However, roles of the individual HCV
      proteins in anti-interferon action are still not well understood. We have
      isolated an HCV strain, HCV-K, from a patient with acute hepatitis. Nucleotide
      sequencing of the entire genomic DNA of HCV-K revealed that the isolate belongs
      to the genotype 1b, which is generally resistant to interferon therapy. In the
      present study, we expressed individual HCV-K proteins in mammalian cells and
      investigated effects of the proteins on interferon signal transduction. The
      results showed that the core, E1, NS4A, and NS4B proteins suppressed activation
      of interferon stimulation responsive element (ISRE) and gamma activation sequence
      (GAS) reporters. These results suggest that multiple HCV proteins have a function
      in suppression of the anti-viral effect by interferon and may indicate a novel
      role of E1 and NS4B proteins in interferon antagonism.

PMID- 16995493
TI  - The progression of bone and muscle atrophy in mice hind limb with immobilization.
AB  - This study investigated the time course of changes of bone and muscle atrophy in
      mice with immobilization by denervation and fixation. The animals were fifty-two
      male C57 BL/6J mice, aged 10 weeks old. Eight mice were used as the base line,
      and the remaining ones were cut at the sciatic nerve of the left hind limb and
      fixed with a plaster cast. At week 1, 2, 3, and 4 after the operation, a cross
      sectional area of the rectus femoris muscles and bone mechanical strength with a
      three-point bending test of the femur and tibia were measured. The time course of
      changes of the bone mechanical strength and of the cross-sectional area of the
      rectus femoris muscles between the intact and experimental limbs in each period
      compared with the control limbs, was determined. The bone mechanical strength of
      the femur, tibia, and the cross-sectional area of the rectus femoris muscles of
      the experimental limbs significantly decreased compared with those of the intact
      limbs at week 4, 3, 2 and 1 after the operation (p<0.05). Compared with the
      intact limbs, the bone mechanical strength and the cross-sectional area of the
      rectus femoris muscles of the experimental limbs declined approximately 10% and
      30%, respectively, during the experiment (p<0.05). It was demonstrated that bone
      and muscle atrophy occurred at an early stage after immobilization by denervation
      and fixation, and that both types of atrophy progressed simultaneously in the
      present study.

PMID- 16995494
TI  - Distribution and change of collagen types I and III and elastin in developing leg
      muscle in rat.
AB  - The distribution of collagen types I and III and elastin in the developing leg
      muscles were studied by immunohistochemistry in rat. From 0-day to 8-weeks old,
      the size of the gastrocnemius and plantaris muscles increased. The muscle
      connective tissue developed in the order of epimysium, perimysium and finally
      endomysium. The epimysium contained a considerable amount of collagen types I and
      III and some elastin in the neonates. These components in the epimysium remained
      almost unchanged in their distribution during development. The perimysium had
      little collagen type I and III or elastin at 0 day. Collagen type I and elastin
      slightly increased around 2 and 1 week, respectively, and returned to the
      previous levels. Collagen type III, however, increased and became abundant after
      1 week. In the endomysium, the amounts of collagen type I and elastin were slight
      during postnatal growth, while collagen type III gradually increased after 2
      weeks. The intramuscular tendons consistently showed intense reactivity for
      collagen type I and weak staining for elastin, whereas the staining for collagen
      type III decreased after 1 week and was finally restricted to the surface of
      intramuscular tendons. This study clearly demonstrated that the distribution of
      collagens, but not of elastin, significantly changed during development. The
      increase in collagen type III in the perimysium and endomysium, and its decrease
      in the intramuscular tendons probably reflect functional demands imposed on these
      connective tissues, i.e., shear forces in the former two and tensile loading in
      the latter.

PMID- 16995495
TI  - Sciatic hernia with an early-stage adenocarcinoma of the appendix: report of a
      case.
AB  - Sciatic hernia and early-stage appendiceal adenocarcinoma are rare disorders. We
      report herein a case of an early stage of appendiceal adenocarcinoma found
      incidentally during an operation for sciatic hernia. An 80-year-old woman was
      admitted to our hospital with abdominal distension. Abdominal computed tomography
      showed a small bowel obstruction and a small bowel loop through the right sciatic
      foramen outside the pelvic cavity. During an operation for the repair of the
      sciatic hernia, a deformed appendix was found incidentally and a simple
      appendectomy was also performed. Histological examination of the excised appendix
      showed well-differentiated adenocarcinoma confined to the mucosal layer in a
      tubulo-villous adenoma. At 13-month follow-up, the patient is doing well without
      evidence of recurrence or metastasis.

PMID- 16995496
TI  - Gynecologic abscess: CT-guided percutaneous drainage.
AB  - A 42-year-old woman with recurrent bilateral endometrial ovarian cystoma
      presented with fever and pelvic pain caused by a tubo-ovarian abscess (TOA),
      which was resistant to several varieties of intravenous and oral antibiotics for
      2 weeks (Case 1). Computed tomography (CT)-guided diagnostic aspiration for a
      rapid enlarged right ovarian cystoma through a transabdominal route confirmed
      that it had developed into a TOA. Subsequent percutaneous abscess drainage (PAD)
      and irrigation for 3 days were successful. One-year follow-up revealed no
      recurrence of TOA. A 58-year-old woman with recurrent cervical cancer after
      external radiation therapy (RT) presented with fever, confusion and tremor caused
      by pyometra (Case 2). Since transvaginal drainage was impossible due to cervical
      os obstruction, the patient had undergone CT-guided transabdominal PAD and
      irrigation for a month. Thereafter, the clinical findings improved and a
      tracheloplasty was performed to prevent recurrence. CT-guided PAD may be a useful
      treatment option for gynecologic abscess as a diagnostic aspiration, a
      temporizing procedure until surgery, or an alternative surgery.

PMID- 16995498
TI  - These doctors say No to execution.

PMID- 16995497
TI  - Feds to hospitals: it's okay to help docs get IT.

PMID- 16995499
TI  - Katrina year 1. The big difficult.

PMID- 16995500
TI  - Watch your tone of voice.

PMID- 16995501
TI  - For his third career, he choose medicine.

PMID- 16995502
TI  - Making meds affordable.

PMID- 16995504
TI  - Make all your instructions crystal clear.

PMID- 16995503
TI  - What would you do? New issues in medical ethics.

PMID- 16995505
TI  - Validation of a tertiary model for predicting variation of Salmonella typhimurium
      DT104 (ATCC 700408) growth from a low initial density on ground chicken breast
      meat with a competitive microflora.
AB  - Growth of a multiple antibiotic-resistant strain (ATCC 700408) of Salmonella
      Typhimurium definitive phage type 104 (DT104) from a low initial density (10(0.6)
      most probable number [MPN] or CFU/g) on ground chicken breast meat with a
      competitive microflora was investigated and modeled as a function of time and
      temperature (10 to 40 degrees C). MPN and viable counts (CFU) on a selective
      medium with four antibiotics enumerated the pathogen. Data from five replicate
      challenge studies per temperature were combined and fit to a primary model to
      determine maximum specific growth rate (micro), maximum population density
      (Nmax), and the 95% prediction interval (PI). Nonlinear regression was used to
      obtain secondary models as a function of temperature for micro, Nmax, and PI,
      which ranged from 0.04 to 0.4 h(-1), 1.6 to 9.4 log MPN or CFU/g, and 1.4 to 2.4
      log MPN or CFU/g, respectively. Secondary models were combined with the primary
      model to create a tertiary model for predicting variation (95% PI) of pathogen
      growth among batches of ground chicken breast meat with a competitive microflora.
      The criterion for acceptable model performance was that 90% of observed MPN or
      CFU data had to be in the 95% PI predicted by the tertiary model. For data
      (n=344) used in model development, 93% of observed MPN and CFU data were in the
      95% PI predicted by the tertiary model, whereas for data (n=236) not used in
      model development but collected using the same methods, 94% of observed MPN and
      CFU data were in the 95% PI predicted by the tertiary model. Thus, the tertiary
      model was successfully verified against dependent data and validated against
      independent data for predicting variation of Salmonella Typhimurium DT104 growth
      among batches of ground chicken breast meat with a competitive microflora and
      from a low initial density.

PMID- 16995506
TI  - Thermal injury and recovery of Salmonella enterica serovar enteritidis in ground
      chicken with temperature, pH, and sodium chloride as controlling factors.
AB  - Cells of Salmonella enterica serovar Enteritidis were grown at 25 and 35 degrees
      C, heat injured (55, 60, and 62.5 degrees C), and recovered in tryptic soy broth
      (TSB) at various NaCl concentrations (2.0 and 3.5%) and pH levels (5.5 and 6.5).
      To assess the interactions of growth temperature, heating temperature, NaCl
      concentration and pH on the thermal injury and recovery of Salmonella Enteritidis
      in ground chicken, a randomized design with each experimental combination was
      used. When a logistic equation for nonlinear survival curves was used, D-values
      of cells of Salmonella Enteritidis grown at 25 degrees C were 7.60, 5.73, and
      4.81 min at 55, 60, and 62.5 degrees C, respectively. For cells grown at 35
      degrees C, the D-values were 12.38, 7.45, and 5.70 min at 55, 60, and 62.5
      degrees C. The influence of tryptic soy agar and double modified lysine agar
      (DMLIA) on the recovery of heat-injured cells was determined. Recovery was
      significantly reduced on DMLIA at increased pH levels and NaCl concentrations.
      Higher numbers of cells were recovered in TSB with 2.0% NaCl than in TSB with
      3.5% NaCl. It was observed that the rate of recovery of heat-injured cells was
      similar at each pH. Therefore, a pH range of 5.5 to 6.5 does not have a major
      inhibitory effect on the recovery of Salmonella Enteritidis.

PMID- 16995507
TI  - Inactivation of Salmonella serovars in liquid whole egg by heat following
      irradiation treatments.
AB  - Salmonella is a frequent contaminant on eggs and is responsible for foodborne
      illnesses in humans. Ionizing radiation and thermal processing can be used to
      inactivate Salmonella in liquid whole egg, but when restricted to doses that do
      not affect egg quality, these technologies are only partially effective in
      reducing Salmonella populations. In this study, the effect of ionizing radiation
      in combination with thermal treatment on the survival of Salmonella serovars was
      investigated. Of the six Salmonella serovars tested, Salmonella Senftenberg was
      the most resistant to radiation (Dgamma = 0.65 kGy) and heat (D(55 degrees C) =
      11.31 min, z = 4.9 degrees C). Irradiation followed by thermal treatment at 55 or
      57 degrees C improved the pasteurization process. Radiation doses as low as 0.1
      kGy prior to thermal treatments synergistically reduced the D(55 degrees C) and
      D(57 degrees C) of Salmonella Senftenberg 3.6- and 2.5-fold, respectively. The
      D(55 degrees C) and D(57 degrees C) of Salmonella Typhimurium were reduced 2- and
      1.4-fold and those of Salmonella Enteritidis were reduced 2- and 1.6-fold,
      respectively. Irradiation prior to thermal treatment would enable the reduction
      of heat treatment times by 86 and 30% at 55 and 57 degrees C, respectively, and
      would inactivate 9 log units of Salmonella serovars.

PMID- 16995508
TI  - Shedding of escherichia coli O157:H7 by cattle fed diets containing monensin or
      tylosin.
AB  - Monensin and tylosin have activity against gram-positive bacteria, and it has
      been theorized that their effects on the intestinal environment may promote
      proliferation of gram-negative bacteria such as Escherichia coli. Effects of
      these antibiotics on the shedding of E. coli O157:H7 were studied in a feedlot
      environment, using 32 finishing steers. A diet containing 85% barley grain, 10%
      barley silage, and 5% supplement was amended with 33 ppm monensin, 11 ppm
      tylosin, both of these additives, or no additives (control). All steers were
      orally inoculated with 10(10) CFU of a mixture of four strains of nalidixic acid
      resistant E. coli O157:H7. Fecal (grab), oral (mouth swab) and water, water-water
      bowl interface, feed, and pen floor fecal pat samples were collected weekly for
      12 weeks. Prevalence of E. coli O157:H7-positive fecal grab samples did not
      differ (P = 0.26) among treatments, nor did the rate (P = 0.81) or duration (P =
      0.85) of shedding of the organism. Fecal grab samples were positive for E. coli
      O157:H7 more frequently (P < 0.001) than were oral swabs. More (P = 0.02) E. coli
      O157:H7-positive oral swabs were recovered from the tylosin group than from
      controls. E. coli O157:H7 was not detected in any of 47 water samples, but was
      present in 1 of 47 water bowl swabs, 7 of 48 feed samples, and 36 of 48 fecal
      pats. Pulsed-field gel electrophoresis suggested that differences existed among
      inoculated strains in their ability to persist in animals and in the environment.
      However, this study revealed no evidence that dietary inclusion of monensin or
      tylosin, alone or in combination, increased fecal shedding of E. coli O157:H7 or
      its persistence in the environment.

PMID- 16995509
TI  - Establishment of critical hygiene indices for meat cooling processes evaluated by
      a temperature function integration method.
AB  - A temperature function integration technique that involves the calculation of the
      potential growth of Escherichia coli to obtain a process hygiene index (PHI) is
      the New Zealand industry standard method for assessing the potential for growth
      of enteric bacteria during meat cooling processes. The existing criteria to
      determine the acceptability of a cooling process with PHI values take no account
      of the differences between meat products and thus limit processing flexibility. A
      methodology was developed to set criteria for processing acceptability, based on
      the frequency distribution of the indicator organism E. coli number on meat
      carcasses immediately after slaughter (in log2 CFU per square centimeter) and a
      requirement that the E. coli numbers at the end of the cooling process be less
      than or equal to some maximum acceptable level. This methodology was used, along
      with accepted guidelines for maximum acceptable levels of E. coli in the meat and
      measured initial E. coli numbers for the whole New Zealand meat industry, to
      develop a set of PHI criteria that would be satisfied by a good-practice meat
      processing operation. A Monte Carlo modeling approach was used to illustrate the
      implications of these criteria if they had been applied to cooling processes for
      beef and lamb previously evaluated by the authors. If the proposed criteria were
      adopted, the maximum allowable PHI for beef cooling could be higher than that for
      lamb cooling because of the lower initial E. coli numbers found on beef than on
      lamb carcasses.

PMID- 16995510
TI  - Lethality of commercial whole-muscle beef jerky manufacturing processes against
      Salmonella serovars and Escherichia coli O157:H7.
AB  - Thermal processes used in making whole-muscle beef jerky include a drying step,
      which may result in enhanced pathogen thermotolerance and evaporative cooling
      that reduce process lethality. Several salmonellosis outbreaks have been
      associated with beef jerky. In this study, a standardized process was used to
      inoculate beef strips with five-strain cocktails of either Salmonella serovars or
      Escherichia coli O157:H7, to marinate the strips at pH 5.3 for 22 to 24 h at 5
      degrees C, and to convert the strips to jerky using various heating and drying
      regimes. Numbers of surviving organisms were determined during and after heating
      and drying. Salmonella reductions of > or = 6.4 log CFU and similar reductions in
      E. coli O157:H7 were best achieved by ensuring that high wet-bulb temperatures
      were reached and maintained early in the process (51.7 or 54.4 degrees C for 60
      min, 57.2 degrees C for 30 min, or 60 degrees C for 10 min) followed by drying at
      76.7 degrees C (dry-bulb temperature). Processes with less lethality that reduced
      counts of both pathogens by > or = 5.0 log CFU were (i) heating and drying at
      76.7 degrees C (dry bulb) within 90 min of beginning the process, (ii) heating
      for successive hourly intervals at 48.9, 54.4, 60, and 76.7 degrees C (dry bulb),
      and (iii) heating at 51.7 degrees C (dry bulb) and then drying at 76.7 degrees C
      (dry bulb), starting before the product water activity dropped below 0.86. In
      several trials, separate beef strips were inoculated with a commercial
      Pediococcus acidilactici starter culture as a potential surrogate for evaluating
      pathogen thermotolerance. The results of these trials suggested that this
      experimental approach may be useful for in-plant validation of process lethality.

PMID- 16995511
TI  - Recovery methods for detection and quantification of Campylobacter depend on meat
      matrices and bacteriological or PCR tools.
AB  - Campylobacter is one of the main causes of human foodborne bacterial disease
      associated with meat consumption in developed countries. Therefore, the most
      effective approach for recovery and detection of Campylobacter from meat should
      be determined. Two hundred ninety pork skin and chine samples were inoculated
      with Campylobacter jejuni NCTC 11168 and two strains of Campylobacter coli.
      Campylobacter cells were then recovered from suspensions and enumerated by direct
      plating. Campylobacter recovery was evaluated by comparing results for two
      methods of sample collection (swabbing and mechanical pummeling) and three
      recovery fluids (peptone water, 5% glucose serum, and demineralized water). End
      point multiplex PCR was performed to evaluate the compatibility of the recovery
      fluids with direct PCR detection techniques. Mean recovery ratios differed
      significantly between pork skin and chine samples. Ratios were higher for
      mechanical pummeling (0.53 for pork skin and 0.49 for chine) than for swabbing
      (0.31 and 0.13, respectively). For pork skin, ratios obtained with peptone water
      (0.50) and with glucose serum (0.55) were higher than those obtained with
      demineralized water (0.16). Significant differences were not observed for chine
      samples. Direct multiplex PCR detection of Campylobacter was possible with pork
      skin samples. The tools for Campylobacter recovery must be appropriate for the
      meat matrix to be evaluated. In this study, less than 66% of inoculated
      Campylobacter was recovered from meat. This underestimation must be taken into
      account for quantitative risk analysis of Campylobacter infection.

PMID- 16995512
TI  - Isolation and characterization of Yersinia enterocolitica from swine feces
      recovered during the National Animal Health Monitoring System Swine 2000 study.
AB  - A national study was conducted for the isolation of pathogenic Yersinia
      enterocolitica in pig feces in the United States as part of the National Animal
      Health Monitoring System's Swine 2000 study. Fecal samples collected from swine
      operations from September 2000 to March 2001 from 77 production sites in 15 of
      the top 17 swine-producing states were tested for the presence of pathogenic Y.
      enterocolitica. After enrichment of swine fecal samples in irgasan-ticarcillin
      potassium chlorate broth, the enriched cultures were plated on cefsulodin-irgasan
      novobiocin agar for isolation of presumptive Y. enterocolitica. The isolates were
      confirmed as pathogenic Y. enterocolitica by the fluorogenic 5' nuclease PCR
      assay targeting the chromosomal attachment invasion ail gene. Of 2793 fecal
      samples tested, 106 (3.80%) ail-positive strains of Y. enterocolitica were
      isolated. These 106 ail-positive isolates originated from 7 of the 15
      participating states. The predominant serotype O:3 (n = 79 of 106) was
      distributed in five states (n = 5 of 7). Serotype O:5 (n = 27 of 106) was also
      found in five states (n = 5 of 7). All isolates contained the virulence plasmid
      and expressed virulence-associated phenotypic characteristics. These results
      indicate that swine in the United Stares harbor Y. enterocolitica that can
      potentially cause human illness.

PMID- 16995513
TI  - Prevalence and survival of Listeria monocytogenes in Danish aquatic and fish
      processing environments.
AB  - Listeria monocytogenes contamination of ready-to-eat food products such as cold
      smoked fish is often caused by pathogen subtypes persisting in food-processing
      environments. The purpose of the present study was to determine whether these L.
      monocytogenes subtypes can be found in the outside environment, i.e., outside
      food processing plants, and whether they survive better in the aquatic
      environment than do other strains. A total of 400 samples were collected from the
      outside environment, fish slaughterhouses, fish farms, and a smokehouse. L.
      monocytogenes was not detected in a freshwater stream, but prevalence increased
      with the degree of human activity: 2% in seawater fish farms, 10% in freshwater
      fish farms, 16% in fish slaughterhouses, and 68% in a fish smokehouse. The fish
      farms and slaughterhouses processed Danish rainbow trout, whereas the smokehouse
      was used for farm-raised Norwegian salmon. No variation with season was observed.
      Inside the processing plants, the pattern of randomly amplified polymorphic DNA
      (RAPD) types was homogeneous, but greater diversity existed among isolates from
      the outside environments. The RAPD type dominating the inside of the fish
      smokehouse was found only sporadically in outside environments. To examine
      survival in different environments, L. monocytogenes or Listeria innocua strains
      were inoculated into freshwater and saltwater microcosms. Pathogen counts
      decreased over time in Instant Ocean and remained constant in phosphate-buffered
      saline. In contrast, counts decreased rapidly in natural seawater and fresh
      water. The count reduction was much slower when the natural waters were
      autoclaved or filtered (0.2-microm pore size), indicating that the pathogen
      reduction in natural waters was attributable to a biological mechanism, e.g.,
      protozoan grazing. A low prevalence of L. monocytogenes was found in the outside
      environment, and the bacteria did not survive well in natural environments.
      Therefore, L. monocytogenes in the outer environment associated with Danish fish
      processing is probably of minor importance to the environment inside a fish
      production plant.

PMID- 16995514
TI  - Daily variability of Listeria contamination patterns in a cold-smoked salmon
      processing operation.
AB  - An understanding of Listeria transmission and contamination patterns in
      processing environments of ready-to-eat foods is critical for improving control
      of Listeria monocytogenes. A cold-smoked fish processing operation was the site
      used to study variability in Listeria contamination in a processing environment
      associated with a ready-to-eat food product throughout one production week (five
      consecutive days). Intensive testing was conducted on finished products and
      environmental samples collected at the beginning, middle, and end of each working
      day. A total of 20 finished products and 22 to 36 environmental samples were
      collected at each sampling time, and an additional 12 environmental samples were
      collected on days 4 and 5. Overall, a total of 782 samples, 300 finished products
      and 482 environmental samples, were tested. All samples were collected from
      processing steps after smoking, including skinning, trimming, slicing, staging,
      and packing. A total of 28 finished and 57 environmental samples (9.3 and 11.8%,
      respectively) were positive for Listeria spp. (including 1 and 5 samples positive
      for L. monocytogenes, respectively). DNA sequencing of the sigB gene allowed
      differentiation of eight Listeria subtypes. Listeria prevalence varied
      significantly between days, and a high prevalence in both environmental samples
      and finished products on day 3 was likely associated with a point source
      contamination event by a single Listeria welshimeri subtype. There were no
      consistent differences in Listeria prevalence among samples collected from the
      beginning, middle, and end of the production day, but subtype data often revealed
      unique contamination patterns for samples collected at different times of a given
      day. Listeria contamination patterns and prevalences were highly variable between
      days and within a given day. These findings indicate that chance events play an
      important role in the contamination of finished products, thus complicating
      efforts to define Listeria transmission patterns in processing environments
      associated with ready-to-eat foods.

PMID- 16995515
TI  - Potassium lactate combined with sodium diacetate can inhibit growth of Listeria
      monocytogenes in vacuum-packed cold-smoked salmon and has no adverse sensory
      effects.
AB  - Growth of Listeria monocytogenes in ready-to-eat fish products such as cold
      smoked salmon is an important food safety issue. The objective of this study was
      to evaluate the antilisterial activity of potassium lactate (PL) in combination
      with sodium acetate (SA) or sodium diacetate (SDA) in cold-smoked salmon and to
      determine whether these compounds could be incorporated easily into the
      formulations and technology currently used by processors. A commercial brine
      injector was used to inject salmon filets with either saturated saline brine or
      saturated saline brine supplemented with combinations of PL and SA (PURASAL Opti.
      Form PA 4) or PL and SDA (PURASAL Opti. Form PD 4). In the brine-injected cold
      smoked salmon, 2.1% (water phase) PL and 0.12% (water phase) SDA delayed the
      growth of L. monocytogenes for up to 42 days of vacuum-packaged storage at 10
      degrees C. Storage at 25 degrees C for 6 h resulted in only a 1-log CFU/g
      increase in L. monocytogenes. Treatments with lower concentrations of PL and SDA
      or similar concentrations of PL and SA resulted in an extended lag phase and
      slower growth of L. monocytogenes. It was not possible to incorporate more than
      2% (water phase) PL while ensuring a minimum of 3% (water phase) NaCl in the
      finished product because PL decreased the solubility of NaCl. Sensory analyses
      revealed that the preservatives did not negatively affect flavor or odor. The
      combination of PL and SDA is therefore a viable technology for preventing L.
      monocytogenes growth on cold-smoked salmon.

PMID- 16995516
TI  - Efficacy of electrolyzed water in the inactivation of planktonic and biofilm
      Listeria monocytogenes in the presence of organic matter.
AB  - The ability of electrolyzed (EO) water to inactivate Listeria monocytogenes in
      suspension and biofilms on stainless steel in the presence of organic matter
      (sterile filtered chicken serum) was investigated. A five-strain mixture of L.
      monocytogenes was treated with deionized, alkaline EO, and acidic EO water
      containing chicken serum (0, 5, and 10 ml/liter) for 1 and 5 min. Coupons
      containing L. monocytogenes biofilms were also overlaid with chicken serum (0,
      2.5, 5.0, and 7.5 ml/liter) and then treated with deionized water, alkaline EO
      water, acidic EO water, alkaline EO water followed by acidic EO water, and a
      sodium hypochlorite solution for 30 and 60 s. Chicken serum decreased the
      oxidation-reduction potential and chlorine concentration of acidic EO water but
      did not significantly affect its pH. In the absence of serum, acidic EO water
      containing chlorine at a concentration of 44 mg/liter produced a > 6-log
      reduction in L. monocytogenes in suspension, but its bactericidal activity
      decreased with increasing serum concentration. Acidic EO water and acidified
      sodium hypochlorite solution inactivated L. monocytogenes biofilms to similar
      levels, and their bactericidal effect decreased with increasing serum
      concentration and increased with increasing time of exposure. The sequential 30-s
      treatment of alkaline EO water followed by acidic EO water produced 4- to 5-log
      reductions in L. monocytogenes biofilms, even in the presence of organic matter.

PMID- 16995517
TI  - Comparison of media and sampling locations for isolation of Listeria
      monocytogenes in queso fresco cheese.
AB  - Listeriosis associated with Hispanic-style soft cheese is an ongoing public
      health concern. Although rapid detection methods based on molecular and
      immunological technologies have been applied successfully for detecting Listeria
      monocytogenes in foods, obtaining isolates of the pathogen is a critical
      procedure for epidemiologic studies and regulatory analysis. Oxford agar, a
      medium recommended by the U.S. Food and Drug Administration Bacteriological
      Analytical Manual (BAM) to isolate L. monocytogenes from cheese, is unable to
      differentiate L. monocytogenes from other Listeria species. Hence, two selective
      isolation media, L. monocytogenes blood agar (LMBA) and Rapid 'L. mono agar
      (RLMA), were compared with Oxford agar for isolating L. monocytogenes from
      cheese. Queso fresco cheese was inoculated at 10(0) or 10(1) CFU/g with a five
      strain mixture of L. monocytogenes or with the five-strain L. monocytogenes
      mixture and Listeria innocua. Cheese samples were stored at 21, 12, and 4 degrees
      C and Listeria counts were determined at 3, 7, and 10 days; 7, 10, 14, 21 days;
      and 2, 4, 8, and 12 weeks postinoculation, respectively. Surface and interior
      cheese samples as well as liquid exudate produced during storage were assayed
      individually to determine differences in Listeria contamination at different
      sampling locations. L. monocytogenes was more easily differentiated from L.
      innocua on RLMA than LMBA and Oxford agar. Similar L. monocytogenes counts (ca.
      10(4) CFU/g) were obtained on the last sampling day on the surface and interior
      of cheese samples (P > 0.05) for all storage temperatures and both initial
      inoculation levels, but smaller cell numbers were detected in the exudate
      produced during storage. In addition, simultaneous inoculation of L. innocua with
      L. monocytogenes did not affect the final L. monocytogenes counts in the cheese.
      The amount of exudate released from the cheese and decrease of pH correlated with
      storage temperature. More exudate was produced and a greater decrease of pH
      occurred at 21 degrees C than at 12 or 4 degrees C. Our results indicate that
      RLMA is a suitable medium for isolating L. monocytogenes from queso fresco
      cheese. Higher counts of L. monocytogenes were obtained from surface and interior
      samples of cheese than from the exudate of the cheese during storage. In
      addition, pH may be a useful indicator of improperly stored queso fresco cheese.

PMID- 16995518
TI  - Virulence of Listeria monocytogenes isolates from humans and smoked salmon,
      peeled shrimp, and their processing environments.
AB  - The virulence of 82 Listeria monocytogenes isolates from human cases and cold
      smoked salmon, cooked peeled shrimp, and their production environments was
      assessed using the plaque-forming assay and a subcutaneous inoculation test in
      mice. These isolates were previously typed using serotyping and pulsed-field gel
      electrophoresis. The isolates from food-production environments were collected in
      several surveys over the period of 5 years. Sixty-eight (99.8%) of 69 isolates
      tested from food and food-processing environments were considered virulent while
      only one was avirulent. All clinical isolates (13) were highly virulent. The
      isolates were from raw materials, final products, and the production environment.
      This stresses the importance of hygiene in the processing environment as well as
      among personnel to avoid contamination of the final product.

PMID- 16995519
TI  - Staphylococcus aureus growth and enterotoxin production during the manufacture of
      uncooked, semihard cheese from cows' raw milk.
AB  - Staphylococcus aureus growth and enterotoxin production during the manufacture of
      model Saint-Nectaire, Registered Designation of Origin Saint-Nectaire, and
      Registered Designation of Origin Salers cheeses, three types of uncooked,
      semihard, raw milk cheese, were investigated. Coagulase-positive staphylococci
      (SC+) grew rapidly during the first 6 h. Between 6 and 24 h, counts increased by
      less than 0.5 log CFU/ml. Raw milk counts ranged from undetectable (<10 CFU/ml)
      to 3.03 log CFU/ml. Maximal levels reached in cheese on day 1 ranged from 2.82 to
      6.84 log CFU/g. The level of SC+ after 24 h was mainly influenced by the milk
      baseline SC+ level (correlation coefficient, r > 0.80) but pH at 6 h influenced
      the SC+ growth observed between 6 and 24 h (r > 0.70). Thus, the initial level of
      SC+ in raw milk should be maintained below 100 CFU/ml and best below 40 CFU/ml.
      To limit growth, acidification should be managed to obtain pH values around or
      below 5.8 at 6 h in Saint-Nectaire cheeses and around or below 6.3 at 6 h in
      Salers cheeses. Enterotoxins were only detected in two Salers cheeses whose SC+
      counts on day 1 were 5.55 log CFU/g and 5.06 log CFU/g, respectively, and whose
      pH values at 6 h were high (approximately 6.6 and 6.5, respectively).

PMID- 16995520
TI  - Effects of chitosan and a low-molecular-weight chitosan on Bacillus cereus and
      application in the preservation of cooked rice.
AB  - Shrimp chitosan with 95% deacetylation and low-molecular-weight chitosan (LMWC)
      isolated from chitosan hydrolysate were investigated for their effects on the
      growth of Bacillus cereus and for use in the preservation of cooked rice. Four
      strains of Bacillus cereus were used: standard strain BCRC 10603 and three
      isolates (nos. 1 through 3) from cooked rice. The antibacterial activity of
      chitosan against B. cereus was greatly decreased when the reaction pH was changed
      from 6.0 to 7.0, but LMWC activity was less affected by this pH change. The
      susceptibility of B. cereus cells to chitosan decreased with increasing of cell
      age, in accordance with the relative electronegativity of the cell surface. B.
      cereus spores were more sensitive to LMWC and chitosan than were vegetative
      cells. Addition of 80 ppm LMWC and chitosan in sterile saline (pH 7.0) greatly
      reduced the D-value for the tested four strains at 90 degrees C from 30.77 to
      46.51 min to 7.47 to 10.17 min and 4.68 to 7.91 min, respectively, and at 100
      degrees C from 1.95 to 2.56 min to 0.89 to 0.93 min and 0.72 to 0.80 min,
      respectively. Addition of 2,000 ppm LMWC to raw rice water before steam cooking
      effectively inhibited increases in total aerobic bacteria and B. cereus in cooked
      rice stored at 37 and 18 degrees C.

PMID- 16995521
TI  - Occurrence of pathogens in raw and ready-to-eat meat and poultry products
      collected from the retail marketplace in Edmonton, Alberta, Canada.
AB  - A total of 800 meat and poultry products were purchased from the retail
      marketplace in Edmonton, Alberta, Canada. The products consisted of raw ground
      beef, chicken legs, pork chops, and ready-to-eat fermented sausage, roast beef,
      processed turkey breast, chicken wieners, and beef wieners. The samples were
      analyzed to determine the prevalence of Shiga toxin-producing Escherichia coli,
      Salmonella, Campylobacter spp., and Listeria monocytogenes. Shiga toxin-producing
      E. coli 022: H8 was found in one raw ground beef sample. Salmonella and
      Campylobacter were found in 30 and 62% of raw chicken legs, respectively. L.
      monocytogenes was found in 52% of raw ground beef, 34% of raw chicken legs, 24%
      of raw pork chops, 4% of fermented sausages, 3% of processed turkey breast, 5% of
      beef wieners, and 3% of chicken wieners. The occurrence of pathogens in this
      study is similar to that in retail products in many other international locales.

PMID- 16995522
TI  - Porcine blood cell concentrates for food products: hygiene, composition, and
      preservation.
AB  - The objective of this study was to determine whether porcine blood cell
      concentrates (BCC) can be produced and stored using hygienic measures independent
      of the temperature acting upon the substrate. A number of additives widely
      accepted by the consumer (NaCl, sugars, food-grade acids) were used to form so
      called hurdles (water activity [a(w)], pH) to spoilage, and their impact was
      tested on microbiological and sensory parameters of the BCC. BCC, whole blood,
      plasma, and the anticoagulant were collected on 23 days in a slaughterhouse. The
      BCC with the additives were stored for 27 days at + 3 degrees C and at +20
      degrees C. Microbiological and chemical tests were carried out on the raw
      materials, and a(w) and the pH values of the stored BCC combinations were
      determined; the combinations were also submitted to sensory testing. The amounts
      of protein (33.4%) and hemoglobin (29.5 g/dl) in the BCC were significantly
      higher than in whole blood (19.4%; 13.8 g/dl). The mean total aerobic plate count
      was similar in all three substrates. However, the highest count (4.83 log CFU/g)
      was found in BCC; the count was lower in whole blood (4.62 log CFU/g) and lowest
      in plasma (4.22 log CFU/g). Storability (defined as a count of <5 log CFU/g) for
      27 days at +20 degrees C was achieved only with two additive types: 15% NaCl and
      10% NaCl plus 10% glucose plus 1% of a food-grade acid. Spoilage of the BCC was
      inhibited by an a(w) of 0.824 (with 15% NaCl) and by the combination of a(w) 0.87
      and a pH of 5 (with 10% NaCl, 10% sugar, 1% acid). Both substrates retained their
      red color and fresh odor over the entire storage time.

PMID- 16995523
TI  - Characterization of the microbial flora in disinfecting footbaths with
      hypochlorite.
AB  - Change or disinfection of footwear are measures to prevent cross contamination
      between areas with low and high hygienic levels in the food industry. The
      efficacy of disinfecting footwear is not well documented. Samples of used
      disinfectant and from swabbing of corners after draining were taken from
      disinfecting footbaths containing chlorine in four Norwegian cheese factories.
      Bacteria were present in 9 of 12 footbaths and more positive samples were found
      from swab samples than from used disinfectant. The microbial flora in footbaths
      varied between the dairies. In two dairies, the flora was dominated by
      Pseudomonas spp. and Acinetobacter spp., respectively. In the third dairy, both
      Bacillus spp. and Staphylococcus spp. were present and in the fourth dairy, the
      flora was diverse (Acinetobacter sp., Enterococcus faecalis, Klebsiella
      pneumoniae, and Bacillus sp.). The strains were not resistant to the recommended
      user concentration of chlorine in bactericidal suspension or surface tests. The
      degree of attachment to plastic varied between strains and species and bacteria
      attached to surfaces were in general more resistant than suspended bacteria. The
      results of the survey indicated that disinfecting footbaths containing chlorine
      may act as contamination sources in food factories and should not be used without
      regular hygienic monitoring.

PMID- 16995524
TI  - Use of electrolyzed water ice for preserving freshness of pacific saury
      (Cololabis saira).
AB  - The effects of electrolyzed water ice (EW-ice), compared with traditional tap
      water ice (TW-ice), on the microbiological, chemical, and sensory quality of
      Pacific saury (Cololabis saira) stored for a period of up to 30 days at 4 degrees
      C were evaluated. EW-ice with active chlorine at a concentration of 34 mg/kg was
      prepared from weak acidic electrolyzed water, whose pH, oxidation-reduction
      potential, and chlorine content were 5, 866 mV, and 47 mg/liter, respectively.
      Microbiological analysis showed that EW-ice, compared with TW-ice, markedly
      inhibited the growth of both aerobic and psychrotrophic bacteria in saury flesh
      during refrigerated storage, primarily because of the action of active chlorine.
      Chemical analysis revealed that EW-ice retarded the formation of volatile basic
      nitrogen and thiobarbituric acid-reactive substances and reduced the accumulation
      of alkaline compounds in the fish flesh in comparison with TW-ice. Sensory
      analysis confirmed that the freshness of saury was better preserved in EW-ice
      than in TW-ice and showed that the saury stored in EW-ice had a shelf life that
      was about 4 to 5 days longer than the fish stored in TW-ice.

PMID- 16995525
TI  - Growth-inhibiting activity of active component isolated from Terminalia chebula
      fruits against intestinal bacteria.
AB  - The growth-inhibitory activity of materials derived from the fruit of Terminalia
      chebula was evaluated against six intestinal bacteria by means of an impregnated
      paper disk agar diffusion method. The butanol fraction of T. chebula extract had
      profound growth-inhibitory activity at a concentration of 5 mg per disk. The
      biologically active component isolated from the T. chebula fruits was identified
      with a variety of spectroscopic analyses as ethanedioic acid. The growth
      responses varied in accordance with the bacterial strain, chemical, and dosage
      tested. In a test with concentrations of 2 and 1 mg per disk, ethanedioic acid
      had strong and moderate inhibitory activity against Clostridium perfringens and
      Escherichia coli, respectively, with no associated adverse effects on the growth
      of the four tested lactic acid-producing bacteria. Ellagic acid derived from T.
      chebula fruits exerted a potent inhibitory effect against C. perfringens and E.
      coli, but little or no inhibition was observed with treatments of behenic acid, P
      caryophyllene, eugenol, isoquercitrin, oleic acid, ca-phellandrene, 3-sitosterol,
      stearic acid, a-terpinene, terpinen-4-ol, terpinolene, or triacontanoic acid.
      These results may be an indication of at least one of the pharmacological
      properties of T. chebula fruits.

PMID- 16995526
TI  - A reverse transcriptase PCR technique for the detection and viability assessment
      of Kluyveromyces marxianus in yoghurt.
AB  - A fast and sensitive reverse transcriptase PCR (RT-PCR) method was developed for
      the detection of viable Kluyveromyces marxianus in yoghurt. Yeast-specific
      primers were used with the RT-PCR to evaluate the suitability of 18S rRNA as a
      target for the detection of viable yeasts in pure culture and yoghurt. The RT-PCR
      assay was able to detect down to 10(2) CFU ml(-1) in yoghurt samples contaminated
      with viable yeast cells. Application of the RT-PCR method to commercial yoghurt
      samples demonstrated the utility of this technique for detection of low
      concentrations of viable yeast cells in naturally contaminated dairy products.
      The 18S rRNA molecule is an appropriate target for cell viability assessment
      because of its limited persistence after cell death and the resultant high level
      of sensitivity of the assay.

PMID- 16995527
TI  - Effect of heat treatment on hepatitis A virus and norovirus in New Zealand
      greenshell mussels (Perna canaliculus) by quantitative real-time reverse
      transcription PCR and cell culture.
AB  - Quantitative real-time reverse transcription PCR (qRT-PCR) and cell culture (50%
      tissue culture infectious dose [TCID50]) were used to determine the effect of
      heat treatments on norovirus and hepatitis A virus (HAV) in the New Zealand
      Greenshell mussel (Perna canaliculus). Since it is common practice to cook
      mussels until the shells open, internal temperatures and opening times of mussels
      on boiling and steaming were determined at regular time intervals. Fifty mussels
      in batches of six were exposed to boiling and steaming. A mean internal
      temperature of 90 degrees C (recommended for virus inactivation when maintained
      for 90 s) was reached after boiling for 170 s, with all 50 mussels open at 210 s.
      For steaming, the mean internal temperature achieved was only 83 degrees C after
      300 s, and all 50 mussels were open. When mussels were steamed for 180 s (mean
      internal temperature of 63 degrees C), a significant 1.5-log decrease in the HAV
      titer (log TCID50) was observed. Following the immersion of mussels in boiling
      water for 180 s (mean internal temperature of 92 degrees C), no viable HAV was
      detected. For both boiling and steaming experiments, there was no significant
      change in the norovirus or HAV qRT-PCR titers compared with the controls. Our
      results show that when New Zealand Greenshell mussels open on heating, their
      internal temperature may not reach the parameters required for virus
      inactivation. Immersion for a minimum of 3 min in boiling water rather than
      steaming is recommended to reduce the risk of viral foodborne illness from
      contaminated shellfish.

PMID- 16995528
TI  - Biocontrol of aflatoxins B1, B2, G1, G2, and fumonisin B1 with 6,7
      dimethoxycoumarin, a phytoalexin from Citrus sinensis.
AB  - Phytoalexins (stress-induced compounds) from Citrus sinensis cultivar Valencia
      were screened for antifungal and antimycotoxic activity against a test organism
      (Cladosporium cladosporoides) and mycotoxin-producing fungi Fusarium
      verticillioides and Aspergillus parasiticus. The active compound, a member of the
      coumarin family of compounds, has antifungal and antimycotoxic activities and was
      chemically identified. High-performance liquid chromatography results indicated
      that Valencia oranges contain a trace amount (0.36 microg/g) of scoparone in
      untreated fruit, but concentrations increased in UV-irradiated fruit (15.2
      microg/g). Infection with Penicillium digitatum, a natural spoilage mold of
      citrus fruit, caused a 35.51-microg/g increase in the phytoalexin. UV absorption,
      infrared absorption, and 1H nuclear magnetic resonance spectroscopy revealed that
      this phytoalexin is identical to 6,7-dimethoxycoumarin. This is the first report
      indicating that the stress-induced compound, 6,7-dimethoxycoumarin, isolated from
      P. digitatum-infected Valencia fruit confers resistance against the mycotoxigenic
      fungi A. parasiticus and F. verticillioides and causes a reduction in production
      of fumonisin B1 and aflatoxins G1, G2, B1, and B2.

PMID- 16995529
TI  - Lack of formation of heterocyclic amines in fumes from frying French fries.
AB  - The formation of heterocyclic amines (HAs) in the fumes from frying French fries
      in soybean oil or lard was studied. A high-pressure liquid chromatography method
      was used to determine the various HAs in fumes. Results showed that the yields of
      fumes produced from soybean oil when heated alone for 2 or 4 h were higher than
      from lard; however, a reversed trend was found when frying French fries in
      soybean oil and lard. Most fumes from soybean oil and lard while frying French
      fries were adsorbed onto the condensation apparatus, while the other portions
      were adsorbed onto the wool and glass beads, which were incorporated in our
      experimental design for collecting the fumes. The fumes from soybean oil when
      heated alone were found to contain three HAs, namely, 2-amino-3-methylimidazo[4,5
      f]quinoxaline (IQx), 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ), and 1-methyl
      9H-pyrido[4,3-b ]indole (Harman), whereas two more HAs, 2-amino-3,4
      dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b
      ]indole (Trp-P-1), were generated in lard. Lard was more susceptible to the
      formation of HAs than soybean oil when both were heated alone. No HAs were
      detected in the fumes from French fries fried in soybean oil and lard.

PMID- 16995530
TI  - Mercury content in tinned molluscs (mussel, cockle, variegated scallop, and razor
      shell) normally consumed in Spain, 2005.
AB  - Concentrations of mercury were determined for tinned molluscs (Mollusca,
      Bivalvia), i.e., mussels (Mytilus spp.), cockles (Cerastoderma edule), variegated
      scallops (Chlamys varia), and razor shells (Ensis spp.), consumed in Spain. A
      total of 220 samples were analyzed: 120 mussels, 40 cockles, 24 variegated
      scallops, and 36 razor shells. Samples were obtained weekly from markets in Santa
      Cruz de Tenerife (Canary Islands) over a period of 12 months. All observed
      concentrations of mercury were below the maximum permitted for human consumption
      (0.5 mg/kg) as defined by European Community Decision 93/ 351/CE. Mercury
      concentrations were 27.28 +/- 12.43 microg/kg for mussels, 66.59 +/- 23.53
      microg/kg for cockles, 33.68 +/- 15.76 microg/kg for variegated scallops, and
      21.26 +/- 12.24 microg/kg for razor shells. To evaluate the importance of mercury
      as a food contaminant, the percentage ingested daily, the weight of mercury in
      the diet, and the calculated percentage of this metal in the diet contributed by
      reference species were estimated.

PMID- 16995531
TI  - PCR identification of ruminant tissue in raw and heat-treated meat meals.
AB  - To control the spread of bovine spongiform encephalopathy in cattle through
      contaminated animal feedstuffs, screening of feed products is essential. We
      designed five pairs of primers to identify specifically raw and heat-treated
      tissue from cattle, sheep, goat, deer, and ruminants in general. A forward common
      primer was designed based on a conserved DNA sequence in the mitochondrial 12S
      rRNA-tRNA(val)-16S rRNA gene, and reverse primers were designed to hybridize with
      a species-specific DNA sequence for each species considered. All primers were
      developed to create a specific PCR product small enough (less than 200 bp) to be
      suitable for heat-treated material. To evaluate the effect of heat treatment, a
      severe sterilization condition (133 degrees C at 300 kPa for 20 min) was chosen.
      Species-specific amplicons were obtained from all types of heat-treated meat
      meals. Analysis of laboratory-contaminated vegetable meals revealed that the
      detection limit of the assay was 0.05% for each species analyzed. This PCR-based
      analysis can be used as a routine method for detecting banned animal-derived
      ingredients in raw and heat-treated feedstuffs.

PMID- 16995532
TI  - Inactivation of escherichia coli O157:H7 in cattle drinking water by sodium
      caprylate.
AB  - Escherichia coli O157:H7 is an important foodborne pathogen. Cattle serve as one
      of the major reservoirs of E. coli O157:H7, excreting the pathogen in feces.
      Environmental persistence of E. coli O157:H7 is critical in its epidemiology on
      farms, and the pathogen has been isolated from cattle water troughs. Thus, there
      is a need for an effective method for killing E. coli O157:H7 in cattle drinking
      water. In this study, the efficacy of sodium caprylate for killing E. coli
      O157:H7 in cattle drinking water was investigated. A four-strain mixture of E.
      coli O157:H7 was inoculated (6.0 log CFU/ml) into 100-ml samples of well water
      containing 0, 75, 100, or 120 mM sodium caprylate. Water samples containing 1%
      (wt/vol) bovine feces or feed also were included. The samples were incubated at
      21 or 8 degrees C for 21 days. Water samples were analyzed for viable E. coli
      O157:H7 on days 0, 1, 3, 5, and 7 and weekly thereafter. Triplicate samples of
      each treatment and control were included, and the study was repeated twice. The
      magnitude of E. coli O157:H7 inactivation in water significantly increased (P <
      0.01) with increases in caprylate concentration and storage temperature. At 120
      mM, sodium caprylate completely inactivated E. coli O157:H7 in all the samples
      after 1 to 20 days, depending on the treatments. The presence of feces or feed
      also had a significant effect (P < 0.01) on the antibacterial property of
      caprylate; the presence of feces decreased the antibacterial effect, whereas
      addition of feed enhanced the effect. These results indicate that sodium
      caprylate is effective in killing E. coli O157:H7 in cattle drinking water, but
      detailed cattle palatability studies of water containing caprylate are necessary.

PMID- 16995533
TI  - Preliminary evaluation of flow-through immunocapture followed by real-time PCR
      for the detection of Salmonella serovars on tomato surfaces within 8 hours.
AB  - This study reports a preliminary evaluation of flow-through immunocapture (FTI)
      followed by real-time PCR (FTI-PCR) for the detection of Salmonella serovars on
      tomato surfaces within 8 h. The FTI-PCR method was compared with real-time PCR,
      direct plating of FTI beads on xylose lysine desoxycholate (XLD), and the
      conventional culture method for Salmonella found in the U.S. Food and Drug
      Administration's (FDA) Bacteriological Analytical Manual (BAM). Unwaxed green
      tomatoes were spot inoculated with a five-serovar Salmonella cocktail on smooth
      surfaces at levels of 10(0) to 10(4) CFU per tomato and washed in lactose broth
      (LB) using a shake-rub method. The resulting LB rinse was incubated at 37 degrees
      C for 4 h prior to analysis by FTI-XLD, real-time PCR, or FTI-PCR and for 24 h as
      the first step in the BAM Salmonella culture method. For FTI-XLD, the observed
      lowest detection level (LDL) was 4.6 x 10(1) CFU per tomato. There was no
      significant difference in performance between the FTI-XLD method and the BAM
      Salmonella culture method (P > 0.05); however, the FTI-XLD method reduced the
      overall assay time by 48 h. For real-time PCR and FTI-PCR, the observed LDLs were
      4.6 x 10(1) and 9.2 x 10(0) CFU per tomato, respectively. The FTI-PCR method was
      superior to the BAM Salmonella culture method (P < 0.05) for the detection of
      Salmonella serovars on tomato surfaces and was completed within 8 h.

PMID- 16995534
TI  - Inhibitory effects of Enterococcus strains obtained from a probiotic product on
      in vitro growth of Salmonella enterica serovar enteritidis strain IFO3313.
AB  - Enterococcus faecium and Enterococcus gallinarum strains were isolated from a
      commercial probiotic product and the effects of these strains on the growth of
      Salmonella enterica serovar Enteritidis strain IFO3313 were investigated. Viable
      cell counts of Salmonella Enteritidis in mixed cultures with the probiotic
      product isolate of E. faecium were significantly (P < 0.05) lower than those in
      pure cultures after 6, 8, and 24 h when the cultures were incubated in heart
      infusion broth at 37 and 41 degrees C. Significant differences in viable cell
      counts of Salmonella Enteritidis in mixed cultures with the probiotic product
      isolate of E. gallinarum and those in pure cultures were also observed after 8
      and 24 h at 37 and 41degrees C. Similar observations were shown in mixed cultures
      of Salmonella Enteritidis with the reference strains of E. faecium GIFU8355 and
      E. gallinarum ATCC 49573. Significant differences in viable cell counts of these
      enterococcal strains were not shown among pure and mixed cultures with Salmonella
      Enteritidis. The pH values in pure and mixed cultures were 7.0 or 7.5 throughout
      the experiments. E. faecium strains were found to harbor the genes encoding
      enterocins A and B and showed inhibitory zones with a diameter of 4 to 6 mm
      against growth of Salmonella Enteritidis in the enterocin production assays.
      However, the E. gallinarum strains possessed neither of the enterocin genes
      tested and exhibited no inhibition zone in the enterocin production assays. These
      results indicated that enterococcal strains exhibit inhibitory effects on the
      growth of Salmonella Enteritidis and these effects were due to both enterocin and
      nonenterocin factors.

PMID- 16995535
TI  - Survival of Staphylococcus aureus and Listeria monocytogenes on vacuum-packaged
      beef jerky and related products stored at 21 degrees C.
AB  - In the manufacture of beef jerky, a thermal lethality step is followed by drying
      to prevent growth of pathogenic bacterial postprocessing contaminants on the
      finished product. Recent guidelines from the U.S. Department of Agriculture have
      raised the question of the maximum water activity (a(w)) in jerky products that
      will inhibit growth of pathogenic bacteria. The survival of the potential
      postprocessing contaminants Staphylococcus aureus and Listeria monocytogenes was
      evaluated on 15 vacuum-packaged beef jerky and related products with a(w) values
      ranging from 0.47 to 0.87, just below the 0.88 limit reported for anaerobic
      growth of S. aureus. Small individual product pieces were inoculated on the outer
      surface with five strains each of S. aureus and L. monocytogenes, repackaged
      under vacuum, and stored at room temperature (21 degrees C) for 4 weeks. Pathogen
      numbers were determined before storage and after 1 and 4 weeks. None of the 15
      jerky products supported growth of either pathogen. Counts of S. aureus fell by
      0.2 to 1.8 log CFU after 1 week of storage and by 0.6 to 5.3 log CFU after 4
      weeks of storage. Numbers of L. monocytogenes fell by 0.6 to 4.7 log CFU and by
      2.3 to 5.6 log CFU after 1 and 4 weeks of storage, respectively. Although factors
      other than a(w) may have some effect on pathogen survival, the results of the
      present study clearly support drying beef jerky to an a(w) of < or = 0.87 to
      ensure that bacterial pathogens cannot grow on vacuum-packaged product stored at
      room temperature.

PMID- 16995536
TI  - Leuconostoc carnosum associated with spoilage of refrigerated whole cooked hams
      in Greece.
AB  - A polyphasic taxonomic approach was used to identify a major atypical group of
      gas-forming, arginine-negative lactic acid bacteria associated with spoilage of
      whole (nonsliced) refrigerated (4 degrees C) cooked hams produced in two Greek
      industrial meat plants. Biochemical characterization revealed that the ham
      isolates shared their phenotypic properties with Leuconostoc carnosum, Weissella
      viridescens, and Weissella hellenica. However, gas chromatographic analysis of
      cellular fatty acids clearly differentiated the ham isolates from the Weissella
      spp. None of the isolates contained eicosenoic acid (n-C20:1), which is typically
      synthesized by W. viridescens, but all strains contained high amounts of C 19cycl
      acid, which is absent in W. hellenica and has been found in trace amounts in W.
      viridescens. All strains had similar cellular fatty acid profiles, which were
      qualitatively similar to those of the cellular fatty acids of L. carnosum. In
      addition to the phenotypic and chemotaxonomic tests, three representative
      isolates were studied using a lactic acid bacteria database, which employs 16S
      and 23S HindIII restriction fragment length polymorphism patterns as operational
      taxonomic units in a numerical analysis. The isolate patterns were identical to
      those of the L. carnosum type strain, NCFB 2776T. Based on the polyphasic
      taxonomic approach, the dominating lactic acid bacteria group was identified as
      L. carnosum.

PMID- 16995537
TI  - Activity of Brassica oleracea leaf juice on foodborne pathogenic bacteria.
AB  - Many vegetables of the Cruciferae family have been found to possess antimicrobial
      properties against several microorganisms of clinical importance. In this study,
      we reported the antibacterial effect of Brassica oleracea juice on several food
      borne pathogens. The juice was found to be effective in inhibiting the growth of
      Salmonella Enteritidis, verotoxigenic Escherichia coli O157:H7, E. coli HB
      producing thermolabile toxin, nontoxigenic E. coli, and Listeria monocytogenes,
      but not Enterococcus faecalis. All cauliflower cultivars tested suppressed
      bacterial growth in a dose-dependent manner after 5 h of treatments, and the
      reduction in the number of viable cells ranged from 1 log with a 10% juice
      concentration to more than 3 log with a 20% juice concentration. The foodborne
      bacteria tested were also markedly reduced by isothiocyanates, natural components
      abundant in the genus Brassica, indicating that glucosinolate-derived
      isothiocyanates can play a major role in the antimicrobial activity of
      cauliflower. The antimicrobial effect of juice was reduced in presence of
      cysteine, suggesting that one mechanism of action of the juice involves blocking
      bacterial sulfhydryl groups.

PMID- 16995538
TI  - An internal amplification control system based on primer-dimer formation for PCR
      product detection by DNA hybridization.
AB  - The detection of PCR products by DNA hybridization techniques can suffer from
      inhibition of the amplification process by sample matrix components. We have
      designed a simple internal control system for PCR based on the incorporation of a
      primer pair with complementary 3' ends, resulting in the generation of a unique
      "primer-dimer" detectable by hybridization with a specific capture probe
      immobilized on polyester cloth as part of an array of amplicon-specific probes.
      The inclusion of this primer pair did not adversely affect the amplification and
      subsequent detection of target gene sequences by hybridization with immobilized
      probes in either single gene amplification or multiplex PCR systems. The failure
      to amplify target gene sequences because of the presence of inhibitors was
      mirrored by a failure to amplify the internal control primer-dimer, demonstrating
      the efficacy of this system in identifying the presence of DNA amplification
      inhibitors.

PMID- 16995539
TI  - Mode of inactivation of probiotic bacteria affects interleukin 6 and interleukin
      8 production in human intestinal epithelial-like Caco-2 cells.
AB  - Five lactic acid bacteria and two bifidobacteria strains were heat or irradiation
      inactivated. Inactivated cultures were evaluated for their effects on cytokines
      interleukin (IL) 6 and IL-8 production in human intestinal-like Caco-2 cells. For
      both heat- and irradiation-inactivated cultures, production of IL-6 and IL-8 was
      dependent on the specific microorganism. However, with all of the cultures, both
      IL-6 and IL-8 production was significantly higher (P < 0.05) in Caco-2 cells that
      were treated with heat-inactivated probiotic bacteria compare to the irradiation
      inactivated bacteria. In the majority of the cases, heat-inactivated bacteria
      induced IL-6 and IL-8 production, whereas irradiation-inactivated bacteria
      attenuated both cytokine production. Our results indicate that the same probiotic
      bacteria used in the same cell culture could provide opposite cytokine production
      and immune modulation results based on its mode of inactivation; therefore, it is
      important to describe inactivation methods and conditions in detail when
      characterizing probiotic effects.

PMID- 16995540
TI  - Evaluation of an enzyme immunoassay for the detection of central nervous system
      tissue contamination at the slaughterhouse.
AB  - To protect public health from bovine spongiform encephalopathy, European
      Commission Regulation EC 1139/2003 on monitoring programs and specified risk
      material requires that as of 1 October 2003, each member state has in place a
      sampling plan with an appropriate laboratory test to detect central nervous
      system (CNS) tissue in bovine head meat harvested at slaughterhouses or cutting
      plants. With this study, we wanted to evaluate the accuracy and reliability of an
      enzyme immunoassay, the RIDASCREEN Risk Material 10/5, in targeting a CNS
      specific marker, the glial fibrillary acidic protein. A receiver operating
      characteristics curve was plotted to identify the best cutoff of CNS
      concentration. Reliability was calculated by Cohen's kappa on data from two
      diagnostic sessions. Test performance showed high sensitivity and specificity
      (97.9 and 97.4%, respectively) for a cutoff value between positive and negative
      at a CNS concentration of 0.049%; reliability of test precision was also very
      good. When these criteria are applied, the RIDASCREEN Risk Material 10/5 test
      appears to be a reliable tool for monitoring CNS tissue contamination in meat.
      This diagnostic procedure should therefore be recommended for national
      application in monitoring programs.

PMID- 16995541
TI  - Biogenic amines in Portuguese traditional foods and wines.
AB  - The presence of biogenic amines in foodstuffs is an important food safety problem
      because of the implication of these compounds in food intolerance and
      intoxication. The separation and quantification of biogenic amines in foods is
      normally performed by chromatographic techniques. This review contains
      descriptions of the quantification of biogenic amines in Portuguese traditional
      fermented and/or ripened foods and wines, including Protected Denomination of
      Origin cheeses, dry-cured sausages, and Portuguese wines (including Port wines),
      using different analytical methods based on high-pressure liquid chromatography
      (UV or diode array and/or fluorometric detectors) and gas chromatography (with a
      mass spectrometry detector). The evolution of biogenic amines during
      fermentation, ripening, aging, or storage of those products was also evaluated.
      Biogenic amine concentrations ranged widely within individual food items, and
      storage, transport, and handling conditions can influence to some extent the
      biogenic amines present and their concentrations. Traditional foods are an
      important part of the Portuguese diet, and a high intake of harmful amounts of
      biogenic amines from traditional Portuguese fermented foods is possible. However,
      extensive research is needed to extend the current limited database.

PMID- 16995542
TI  - Performance of the crystalens.

PMID- 16995543
TI  - Standardized analyses of correction of astigmatism.

PMID- 16995544
TI  - Unified formulas for phakic/aphakic intraocular lens and spectacle/cornea power
      conversion.

PMID- 16995545
TI  - Bilateral comparison of conventional versus topographic-guided customized
      ablation for myopic LASIK with the NIDEK EC-5000.
AB  - PURPOSE: To compare visual acuity and higher order aberrations before and after
      myopic LASIK using conventional versus customized ablation. METHODS: This
      prospective, randomized study included 54 myopic eyes in 27 patients who
      underwent bilateral LASIK using the NIDEK EC-5000 excimer laser system (NIDEK
      Technologies, Gamagori, Japan). Customized aspheric treatment zone (CATz)
      treatment was used in one eye (CATz group) and conventional ablation
      (conventional group) was used in the fellow eye. Uncorrected visual acuity (UCVA)
      and higher order aberrations (root-mean-square [RMS] in 4-mm and 6-mm zones) of
      both groups were observed with the NIDEK OPD-Scan aberrometer before and 3 months
      after LASIK. Preoperative mean refractive error was similar for both eyes of each
      patient (P>.05). RESULTS: No statistically significant differences were noted in
      preoperative higher order aberrations (RMS in 4-mm and 6-mm zones) between groups
      (P>.05). No statistically significant difference was noted between pre- and
      postoperative higher order aberrations in the CATz group (P>.05). However, a
      highly statistically significant increase in higher order aberrations was
      observed after conventional ablation (P<.001). There was a statistically
      significant higher increase of higher order aberrations after LASIK in the
      conventional group than the CATz group (P<.05). Postoperative UCVA with both
      conventional and customized ablation was not significantly different (P>.05).
      CONCLUSIONS: LASIK with conventional ablation and CATz ablation resulted in the
      same UCVA. The increase in higher order aberrations after CATz ablation was less
      than after conventional ablation.

PMID- 16995546
TI  - Measurement of contrast sensitivity and glare under mesopic and photopic
      conditions following wavefront-guided and conventional LASIK surgery.
AB  - PURPOSE: To compare contrast and glare vision in a prospective study of eyes
      treated using conventional and wavefront-guided LASIK surgery. The
      reproducibility of a glaremeter device used to quantitatively measure glare and
      halo was also determined. METHODS: Ninety-two eyes of 46 patients underwent
      conventional LASIK surgery and 104 eyes of 52 patients underwent wavefront-guided
      LASIK surgery. Visual acuity, glare disability measured using a glaremeter, and
      contrast sensitivity assessed using a Pelli-Robson chart were measured monthly
      for 6 months postoperatively. Glaremeter testing was performed under both mesopic
      (5.4 +/- 0.4 cd/m2) and photopic (78.3 +/- 4.4 cd/m2) conditions. To evaluate the
      reproducibility of the glaremeter, 36 eyes of 18 nonoperated myopic patients were
      tested. RESULTS: The coefficient of variation and the reliability coefficient for
      the glare test were 13.6% and 95.2%, respectively. The glaremeter showed that
      glare disability under mesopic conditions differed between conventional and
      wavefront-guided LASIK eyes over 6-month follow-up (907.5 +/- 491.5 vs 986.1 +/-
      448.0 pixels preoperatively and 1717.1 +/- 521.2 vs 1407.8 +/- 411.3 pixels at 6
      months, P<.0001). At 6 months, contrast sensitivity log values were 1.62 +/- 0.31
      and 1.78 +/- 0.34 for conventional and wavefront-guided LASIK eyes, respectively
      (P=.010). The visual complaint score was lower in the wavefront-guided LASIK
      group (P=.0116). CONCLUSIONS: Compared to conventional ablation, wavefront-guided
      ablation provided superior outcomes in terms of postoperative glare under mesopic
      conditions, subjective complaints, and contrast sensitivity. In addition, it
      appears the glaremeter can be used for clinical quantitative evaluation of glare
      and halo.

PMID- 16995547
TI  - Relative contribution of central and peripheral aberrations to overall high order
      corneal wavefront aberration.
AB  - PURPOSE: To analyze the influence of specific combinations of corneal high order
      aberrations on the optical image quality of the cornea before and after
      photorefractive keratectomy (PRK) for low to high myopia and myopic astigmatism.
      METHODS: Corneal topography was obtained for 80 eyes that underwent PRK using a
      scanning-spot excimer laser. The eyes were subdivided into three groups according
      to the preoperative refraction. The topographical data were imported into a
      custom software program that combined the Zernike high order terms having the
      same sign and angular frequency up to seventh order for 4-mm and 6-mm pupils, ie,
      coma and spherical aberrations, and midperipheral and peripheral high order
      aberrations. RESULTS: Photorefractive keratectomy induced a significant amount of
      the root-mean-square (RMS) values of the combinations of midperipheral and
      peripheral high order aberrations over the smaller pupil size for deeper myopic
      ablations (P<.05). Over the larger pupil, spherical myopic ablations showed a
      significant increase (P<.05) of the RMS values of coma and spherical aberrations.
      In the astigmatism group, the combination of terms having higher angular
      frequency increased significantly (P<.05) after surgery both over 4-mm and 6-mm
      pupils. CONCLUSIONS: After surface ablation, ablation depth and profile
      significantly influence the distribution and contribution of determined
      combinations of high order aberrations to the overall high order corneal
      wavefront aberration. Terms having high angular frequency were increased
      following large myopic correction and wide treatment zone. Quality of the whole
      corneal optics will be enhanced by designing future ablation profiles to
      compensate for peripheral high order optical aberrations.

PMID- 16995548
TI  - Ultrasound and partial coherence interferometry with measurement of central
      corneal thickness.
AB  - PURPOSE: To compare noncontact pachymeter measurements with ultrasound pachymeter
      measurements and assess their reproducibility. METHODS: Central corneal thickness
      was measured in 104 eyes of 56 patients with three laser interference pachymeters
      (OLCR [Haag Streit, Konitz, Switzerland], OCP [4optics AG, Lubeck, Germany], and
      ACMaster [Carl Zeiss Meditec, Jena, Germany]) and an ultrasound pachymeter (Tomey
      AL2000 [Tomey Corp, Nagoya, Japan]). RESULTS: Compared to the ultrasound
      measurements, the mean difference for the laser interference pachymeter
      measurements were +8.8 microm (standard deviation [SD] 5.68) for the OLCR, -8.0
      microm (SD 5.39) for the OCP, and -0.12 microm (SD 5.88) for the ACMaster.
      Reproducibility could only be estimated as not all of the devices allowed access
      to individual measurements. For all laser interference devices, reproducibility
      was estimated to be approximately 2 microm. Ultrasound measurements yielded a
      reproducibility of approximately 3.4 microm. CONCLUSIONS: Although ultrasound
      pachymeter measurements differed significantly from OLCR and OCP measurements,
      agreement was considered good because the mean differences were <10 microm, and
      the results can be regarded as clinically interchangeable.

PMID- 16995549
TI  - Comparison of corneal thickness measured with optical coherence tomography,
      ultrasonic pachymetry, and a scanning slit method.
AB  - PURPOSE: To investigate the relationship between 1310-nm optical coherence
      tomography (OCT), an ultrasound pachymeter, and the Orbscan II (Bausch & Lomb,
      Rochester, NY) in corneal thickness measurements before and after LASIK. METHODS:
      Twenty-eight eyes of 14 patients with a mean age of 39.9 +/- 8.6 years underwent
      LASIK for correction of myopia with or without astigmatism. Central corneal
      thickness was measured with real-time 1310-nm OCT and Orbscan preoperatively and
      1 day, 1 week, and 1 month postoperatively, and with an ultrasound pachymeter
      preoperatively and 1 month postoperatively. RESULTS: Measurements of corneal
      thickness by all instruments correlated well with one another pre- and
      postoperatively (r value range: 0.87 to 0.94, P<.05); however, there were
      significant differences among these methods (ANOVA: P<.005). Baseline readings
      for ultrasound and Orbscan were similar, as were readings 1 month postoperatively
      for OCT and Orbscan (P>.05). Thickness measured by OCT was thinner than for other
      instruments preoperatively (P<.005) and thicker than Orbscan postoperatively
      (P<.005). Significant corneal thinning (P<.001) was found with all study devices
      1 day after laser ablation. Significant corneal thinning (P<.005) was found with
      OCT and Orbscan 1 week compared to 1 day postoperatively, and thickening (post
      hoc: P<.001) was evident at 1 month compared to 1 week postoperatively.
      CONCLUSIONS: Although the instruments correlated well in measuring corneal
      thickness after LASIK, there were significant differences. All instruments
      indicated corneal swelling and recovery during the first postoperative week and
      thickening at 1 month.

PMID- 16995550
TI  - Binocular visual performance after LASIK.
AB  - PURPOSE: To analyze binocular visual function after LASIK. METHODS: Eye
      aberrometry and corneal topography was obtained for both eyes in 68 patients (136
      eyes). To evaluate visual performance, monocular and binocular contrast
      sensitivity function and disturbance index for quantifying halos were measured.
      Tests were performed under mesopic conditions. RESULTS: Binocular summation and
      disturbance index diminished significantly (P<.0001) after LASIK with increasing
      interocular differences in corneal and eye aberrations. Binocular visual
      deterioration was greater than monocular deterioration for contrast sensitivity
      function and disturbance index. CONCLUSIONS: Binocular function deteriorates more
      than monocular function after LASIK. This deterioration increases as the
      interocular differences in aberrations and corneal shape increase. Improvements
      in ablation algorithms should minimize these interocular differences.

PMID- 16995551
TI  - Macular choroidal neovascularization in myopic eyes after phakic intraocular lens
      implantation.
AB  - PURPOSE: To analyze the development and characteristics of choroidal
      neovascularization in highly myopic patients corrected by the implantation of
      phakic intraocular lenses (PIOLs). METHODS: This retrospective, noncomparative
      interventional case series studied the development of choroidal
      neovascularization in 522 consecutive highly myopic eyes (spherical equivalent
      refraction >-6.00 diopters [D] and/or axial length >26 mm) (323 patients)
      corrected by the implantation of PIOLs, the treatment performed, and the results
      obtained. Parameters evaluated were best spectacle-corrected visual acuity
      (BSCVA) before and after treatment of choroidal neovascularization, and the
      interval between refractive surgery and the development of choroidal
      neovascularization. RESULTS: Follow-up ranged from 12 to 145 months (mean: 60.4
      +/- 39.1 months). In 12 (2.29%) eyes, choroidal neovascularization developed
      after PIOL implantation at a mean interval time of 33.7 +/- 29.6 months (range: 1
      to 87 months). Using Kaplan-Meier analysis, the risk of choroidal
      neovascularization in patients with high myopia corrected by PIOL implantation
      was 0.57% at 5 months, 0.81% at 18 months, 1.31% at 24 months, and 3.72% at 87 to
      145 months. No statistically significant differences were found between patients
      with and without choroidal neovascularization in the following parameters: axial
      length (P=.826), age (P=.296), initial BSCVA (P=.085), spherical equivalent
      refraction (P=.663), and follow-up (P=.955). CONCLUSIONS: Phakic intraocular lens
      implantation for the correction of high myopia does not play a role in the
      development of choroidal neovascularization.

PMID- 16995552
TI  - Higher order ocular aberrations in eyes with myopia in a Chinese population.
AB  - PURPOSE: To describe the characteristics of higher order ocular aberrations of
      adult Chinese eyes with myopia. METHODS: Higher order aberrations in consecutive
      right eyes of 166 Chinese patients with myopia who enrolled for preoperative
      assessment for LASIK were retrospectively reviewed. Wavefront aberrations were
      measured with the Bausch & Lomb Zywave over a 6-mm dilated pupil. The
      correlations between higher order aberrations and myopia, astigmatism, and age,
      respectively, were analyzed. RESULTS: Mean patient age was 32.1 +/- 6.2 years,
      the mean refractive error was sphere -5.23 +/- 1.79 diopters (D) and cylinder 
      1.29 +/- 0.98 D. The mean of the total higher order root-mean-square (RMS) (third
      to fifth order) was 0.49 +/- 0.16 microm. Third-order RMS was largest (mean 0.37
      +/- 0.16 microm), followed by fourth-order RMS (mean 0.29 +/- 0.11 microm). For
      individual higher order Zernike coefficients, spherical aberration (C4(0))
      predominated with a mean of 0.23 +/- 0.14 microm. No correlation was found
      between total higher order RMS and myopia or between total higher order RMS and
      age. Small but statistically significant relationships were found in the
      following groups: age and vertical primary coma (C3(-1))(r=-0.206, P=.008); age
      and spherical aberration (C4(0)) (r=0.196, P=.012); and myopia and horizontal
      trefoil (C3(3)) (r=-0.158, P=.042). CONCLUSIONS: Higher order aberrations varied
      among individuals with myopia. Third-order RMS was the predominant higher order
      aberration. Spherical aberration and vertical primary coma increased slightly
      with age. Our study helps establish ocular aberration standards for Chinese
      refractive surgery candidates.

PMID- 16995553
TI  - Preoperative characteristics of patients undergoing LASIK in 1997 versus 2004 at
      one surgical eye center in China.
AB  - PURPOSE: To compare the preoperative characteristics of LASIK patients undergoing
      surgery in 1997 versus 2004 at one of the principal eye surgical centers in
      China. METHODS: Preoperative data of patients who underwent LASIK in 1997 and
      2004 were recorded and retrospectively compared. RESULTS: In 1997, the mean
      spherical equivalent refraction of the 824 eyes of 428 patients undergoing LASIK
      surgery was -7.30 +/- 4.65 diopters (D), with a mean patient age of 24.67 +/-
      6.76 years. Students represented 45.05% of patients undergoing surgery in 1997.
      In 2004, the mean spherical equivalent refraction of the 8434 eyes of 4286
      patients undergoing LASIK surgery was -6.66 +/- 3.31 D, with a mean patient age
      of 25.20 +/- 6.59 years. Students represented >50% of patients undergoing surgery
      in 2004. There were significant differences in the constitution ratio of
      occupation and the spherical equivalent refractions between 1997 and 2004 (t=
      2.712, chi-squared=25.117, respectively, P<.05). CONCLUSIONS: At our center in
      China, the majority of LASIK patients are young and have myopia ranging from 
      3.00 to -10.00 D. Students were much more likely than any other occupation to
      undergo LASIK. The number of patients undergoing LASIK at our center in China has
      increased exponentially from 1997 to 2004, with an average annual increase in
      surgical volume of approximately 40%.

PMID- 16995554
TI  - Correlation between TGF-beta1 in tears and corneal haze following LASEK and epi
      LASIK.
AB  - PURPOSE: To compare the incidence and degree of corneal haze formation following
      laser subepithelial keratomileusis (LASEK) and epithelial laser in situ
      keratomileusis (epi-LASIK), and examine its correlation with tear film
      transforming growth factor-beta1 (TGF-beta1) levels. METHODS: This prospective,
      interventional, clinical trial included 20 eyes (20 patients) randomly assigned
      to undergo LASEK or epi-LASIK. The level of TGF-beta1 in tear fluid was measured
      preoperatively and 1, 3, and 5 days postoperatively. Corneal haze was graded at 1
      and 3 months after surgery, and the relationship with TGF-beta1 levels was
      determined. RESULTS: Mean preoperative spherical equivalent refraction was -4.50
      +/- 1.44 diopters (D) (range: -1.50 to -6.00 D) for LASEK eyes and -4.90 +/- 1.26
      D (range: -1.75 to -6.00 D) for epi-LASIK eyes. Although mean corneal haze scores
      at 1 month were significantly higher in LASEK-treated eyes than in epi-LASIK
      treated eyes (P=.031), these scores were similar at 3 months (P=.608). Tear fluid
      TGF-beta1 levels were similar in LASEK and epi-LASIK eyes before surgery (P=.458)
      and significantly higher in the LASEK group at 1, 3, and 5 days postoperatively
      (P=.015, P=.023, and P=.039, respectively). A positive correlation was noted
      between tear TGF-beta1 levels on the first postoperative day and the degree of
      corneal haze at 1 month (r=0.501, P=.016). CONCLUSIONS: Less corneal haze was
      noted after epi-LASIK than LASEK. A positive correlation between corneal haze and
      tear fluid TGF-beta1 levels on the first postoperative day suggest a possible
      mechanism for the observed difference.

PMID- 16995555
TI  - Intraocular lens power calculation in high myopic eyes with previous radial
      keratotomy.
AB  - PURPOSE: To determine an accurate method of intraocular lens (IOL) power
      calculation in highly myopic eyes with previous radial keratotomy (RK). METHODS:
      Five eyes that had undergone RK with preoperative myopia >-14.0 diopters (D) were
      studied retrospectively. The keratometric values obtained with the clinical
      history method, contact lens over-refraction method, conventional keratometry,
      adjusted keratometry, and Orbscan II were compared to the true keratometric value
      calculated retrospectively with the SRK/T formula. RESULTS: The true keratometric
      value was closest to that from the contact lens over-refraction method in one eye
      and to the flatter keratometric value between simulated keratometry (Sim K) and
      the 3-mm diameter central zone mean keratometric value obtained with axial
      keratometric power map of Orbscan II in four eyes. CONCLUSIONS: The flatter
      keratometric value between Sim K and the 3-mm zone mean keratometric value from
      Orbscan II was closest to the true postoperative RK keratometric value of the
      central cornea.

PMID- 16995556
TI  - Topography-guided LASIK with the wavelight laser after penetrating keratoplasty.
AB  - PURPOSE: To report a case of topography-guided LASIK in a patient after previous
      penetrating keratoplasty. METHODS: A 20-year-old man who had previous penetrating
      keratoplasty in his right eye for keratoconus and was intolerant to spectacles
      and contact lenses underwent topography-guided LASIK. RESULTS: Three months
      postoperatively, the patient's uncorrected visual acuity in the right eye was
      20/25(+2). Best spectacle-corrected visual acuity was 20/20, with a manifest
      refraction of +0.25 -0.75 x 40 degree. CONCLUSION: Topography-guided LASIK is a
      useful therapeutic modality to address corneal irregularity after penetrating
      keratoplasty.

PMID- 16995557
TI  - The effect of Nd:YAG laser capsulotomy size on refraction and visual acuity.
AB  - PURPOSE: To determine the effect of Nd:YAG laser posterior capsulotomy size on
      refraction and visual acuity. METHODS: A total of 128 pseudophakic eyes (108
      patients) were included in this study and divided into two groups by capsulotomy
      size: 80 eyes had small capsulotomies (<4 mm) without dilating the pupil and 48
      eyes had large capsulotomies (> or = 4 mm and <7 mm) after dilating the pupil.
      Visual acuities and refractive errors were measured preoperatively and 1, 14, 30,
      and 90 days postoperatively. Results were analyzed statistically. RESULTS: The
      change in spherical equivalent refraction was 0.38 +/- 0.52 diopters (D) in the
      small capsulotomy group and 0.22 +/- 0.36 D in the large capsulotomy group. No
      statistically significant differences were noted in spherical equivalent
      refraction change (P=.47) or capsulotomy size (P=.0387) between the two groups.
      CONCLUSIONS: The size of posterior capsulotomy does not significantly affect
      refraction and visual acuity.

PMID- 16995558
TI  - Use of peripheral chatter lines for free-flap alignment during LASIK.
AB  - PURPOSE: To report a case in which an improperly rotated free flap was
      successfully repositioned using peripheral chatter lines as a reference. METHODS:
      A 30-year-old woman with irregular astigmatism as the result of an improperly
      rotated free flap during LASIK underwent repositioning of the corneal flap
      correspondingly along the chatter lines. RESULTS: Best spectacle-corrected visual
      acuity improved from 20/100 to 20/20 following the procedure. Corneal topography
      showed improvement in the astigmatism and the Placido disk pattern. CONCLUSIONS:
      When marks on a free flap are obscured during LASIK, periodic chatter lines can
      be used for realignment if no other landmarks are available.

PMID- 16995559
TI  - Population genomics and dental public health.

PMID- 16995560
TI  - Dental check-up frequency: preferences of Dutch patients.
AB  - OBJECTIVE: In 1995, the requirement to visit the dentist for a check-up every six
      months in The Netherlands was replaced by the obligation to get a routine
      examination no more than once a year. The aim of this study was to determine
      patients' opinions about this change in policy, and to assess their preferences
      regarding frequency and content of regular dental check-up visits. Possible
      associations between patients' preferences for regular dental check-ups and a
      number of antecedent variables, such as dental attitudes, were examined as well.
      BASIC RESEARCH DESIGN: Patients' preferences for regular dental check-ups were
      assessed by means of a questionnaire, containing a 19-item Likert-type scale,
      twelve visual analogue scales and seven forced choice items. Items assessing
      various background variables and a selection of items of the Dental Attitude
      Questionnaire were also added. This questionnaire was administered to patients of
      seven dental practices. A total of 428 patients completed the questionnaire.
      RESULTS: Results indicated that patients prefer to have regular dental check-ups.
      Patients' evaluation of six-monthly dental check-up visits was significantly more
      positive than their evaluation of flexible, individualized, check-up frequencies.
      Factors positively associated with a higher preference for regular dental check
      up visits were female gender, being more satisfied with one's teeth, less
      cynicism toward dental health care professionals and more intrinsic motivation to
      maintain one's oral health. CONCLUSIONS: Patients seem to prefer to attend their
      dentist regularly, at fixed intervals of about six months. This fact should be
      taken into account when deciding about the most appropriate interval between
      dental examinations.

PMID- 16995561
TI  - Caries prevalence of 11.5 year-olds between 1989 and 2001 in a province of North
      Eastern Greece.
AB  - OBJECTIVE & DESIGN: To compare cross-sectional caries prevalence data of 11.5
      year old children over a 13 year period (1989-2001) and to evaluate the maximum
      effect of the applied preventive programme (sealants to 1st molars and 6-year
      health education) on DMFT values during the last five years. PARTICIPANTS: Using
      the records of a Public Health Centre (PHC) in NE Greece, a number (153-250) of
      children aged 11.5-years were selected from each calendar year, constituting 11
      study groups (totalling 2,217 children), stratified by area of residency. METHOD:
      Annual oral health education sessions provided in 1990, a year after the PHC was
      established. Light-cured fissure sealants were systematically mass introduced in
      1996. The same dentist completed all DMFT records in the dental clinic during the
      children's routine visits. DMFT was analysed using two Poisson and two Binomial
      models for both data from all years, and for the last five years. The models had
      as factors: "Time" (year of examination of the study group), "Residency" (semi
      urban, rural lowland, rural highland), number of "Sealed 1st molars" and "Sealed
      posterior teeth". RESULTS: All the factors were highly statistically significant
      (p<0.001). Dental health was found to be good (DMFT=0), improving progressively
      year by year (range 12-50%). The mean DMFT decreased steadily from 4.5 (in 1989)
      to 1.81 (in 2001). The Significant Caries index was almost halved (from 8.08 to
      4.23). CONCLUSION: An important improvement in the caries status of 11.5 year
      olds since 1989 has been demonstrated, irrespective of the residency. The
      systematic application of fissure sealants to all 1st molars, parallel to the
      cumulative effect of the 6-year health education programme per child, played a
      significant role in reducing disparities in disease prevalence, despite the
      difficulty of improving rates of decline when the caries levels are relatively
      low.

PMID- 16995562
TI  - Dental health attitudes and behaviour among dental students in Jordan.
AB  - OBJECTIVE: Examine and compare differences in oral health attitudes and behaviour
      among Jordanian dental students. BASIC RESEARCH DESIGN AND PARTICIPANTS: Cross
      sectional study of 314 dental students was conducted to compare differences in
      oral health behaviour and attitudes among these students in different levels of
      academic education. SETTING: Jordan University of Science and Technology.
      METHODS: Subjects were surveyed using a modified version of the Hiroshima
      University Dental Behavior Inventory (HU-DBI) questionnaire (20 Items).
      Multivariate binary and polytomous logistic regression analyses were performed in
      order to study change of patterns of statements during preclinical and clinical,
      and year of study, respectively. RESULTS: The percentage of students claiming to
      brush their teeth twice daily or more often was four times higher amongst
      clinical students than amongst pre-clinical students.. The odds of visiting a
      dentist only in case of toothache was reduced by a factor of more than three
      among clinical year students (OR 0.30, 95% CI 0.15-0.61). Clinical year students
      rarely complained of bleeding gums after toothbrushing (OR 0.10, 95% CI 0.03
      0.27). On the other hand, a number of items regarding use of dental floss and
      tooth paste, bad breath, colour and appearance of teeth, and cigarette smoking
      was similar between preclinical and clinical students. Evaluation of trends
      during dental studies employing polytomous multivariate logistic regression
      analysis revealed an abrupt change at the end of preclinical studies for items
      characterizing professional attitude. CONCLUSIONS: With advancement in dental
      school, dental student's oral health awareness and attitudes improved in some
      aspects. Preventive dentistry courses should be taught early in the dental
      curriculum of the pre-clinical years.

PMID- 16995563
TI  - Equity in children's utilization of dental services: effect of a children's
      dental care programme.
AB  - OBJECTIVES: To evaluate the long term impact on fairness of children's dental
      care programmes. METHODS: Data were taken from the Health Module of the Spanish
      Disability Interview Survey in 1999 (n=8,049). The probability of visit to a
      dentist and the number of visits are estimated with binary logistic models and
      count data models in order to compare the regions with consolidated dental care
      programmes, PADI regions, with the rest of Spanish regions. The effects of family
      income, residential status and living in small village settings on dental care
      access for both regions are investigated and compared. RESULTS: The scope of the
      dental care programme (PADI) makes a very significant difference. Regions with
      consolidated PADI are by far more equitable than the rest. Once the other
      explanatory factors have been controlled, the percentage of users is by far
      larger in PADI regions, odds ratio 3.47 (95% CI 2.38 to 5.07). In PADI regions
      family income doesn't have any significance in the probability of visits to the
      dentist, odds ratio 1.9 (95% confidence interval 0.92 to 1.81). In non PADI
      regions poorer families have less probability of visiting a dentist, odds ratio
      1.68 (95% CI 1.50 to 1.88). In addition, in each region, inequalities
      discriminating against those children that live in small villages cannot be found
      in PADI regions. CONCLUSIONS: PADI regions have more equity in access to dental
      care. The PADI programme managed to drop any income base discrimination in access
      and succeeded in equalizing access in small villages and in urban areas. The use
      of dental services is very unequal among the population. Public dental care
      programmes for children equalize utilization and strongly contribute to improving
      children's oral health.

PMID- 16995564
TI  - The Japanese version of the Oral Health Impact Profile (OHIP)--validation among
      young and middle-aged adults.
AB  - OBJECTIVE: To validate the Japanese version of the Oral Health Impact Profile
      (OHIP-J) for use among young and middle-aged adults. Evaluating the criterion
      validity was particularly important in this study. METHOD: The original Oral
      Health Impact Profile (OHIP) was translated into Japanese. Data from 6,079
      subjects aged 20-59 were collected by means of a self-administered questionnaire
      and the oral condition records of a sample of workers. The survey involved items
      for the OHIP-J and self-rated oral health, denture wearing, number of missing
      teeth, work type, occupational rank, gender, and age. We adopted a self-rated
      oral health and number of missing teeth as validity criteria for this analysis.
      RESULTS: Using multiple linear regression analysis, the adjusted total OHIP-J
      scores for respondents who rated their oral health as poor were higher than those
      who did not (46.6 vs. 27.6; p<0.001). The variable of missing teeth was
      significantly associated with the OHIP-J total and subscale scores independent of
      gender, age and denture wearing (p<0.001). CONCLUSIONS: These findings suggest
      that the OHIP-J is suitable for assessing the oral health-related quality of life
      of young and middle-aged adults in Japan.

PMID- 16995565
TI  - Whither the "case report and review of the literature"? Bring on research
      networks.

PMID- 16995566
TI  - Medical and psychosexual outcome in women affected by complete gonadal
      dysgenesis.
AB  - BACKGROUND: Prenatal exposure to testicular hormones influences the development
      of brain structures and behavior in many non-human mammalian species. Less
      understood is the role of possessing a Y chromosome, independent of testicular
      hormones, on psychosexual differentiation. HYPOTHESIS: Phenotypic women affected
      by complete gonadal dysgenesis possess a 46,XY chromosome complement and streak
      gonads. This population is suitable to test the influence of an absence of
      androgens and Mullerian inhibiting substance on psychosexual development in
      genetic males. PATIENTS: Three 46,XY women diagnosed with complete gonadal
      dysgenesis participated. METHODS: Psychosexual development, medical outcome and
      knowledge of medical condition were assessed with a written questionnaire and a
      physical examination. RESULTS: All participants were healthy, compliant with
      their hormone therapy, and exhibited female-typical psychosexual development.
      However, participants were poorly informed about their condition and the
      fertility treatment options available to them. CONCLUSIONS: These data indicate
      no obvious role for genes on the Y chromosome, outside of its pseudoautosomal
      region and SRY, on psychosexual differentiation in genetic males who do not
      produce testicular hormones. Greater efforts need to be made to educate affected
      women about their pregnancy options.

PMID- 16995567
TI  - Quality of life and gender role behavior in disorders of sexual differentiation
      in India.
AB  - OBJECTIVE: Culture-specific tools to assess longterm psychosocial outcomes for
      patients with disorders of sexual differentiation are scant. We conducted a study
      to develop tools for evaluating gender role behavior and health related quality
      of life for Indian adolescent patients with intersex disorders. We also studied
      factors important to parents while deciding sex of rearing for their baby.
      METHODS: A 29-item gender role behavior questionnaire and an 18-item health
      related quality-of-life questionnaire were administered to 82 healthy controls,
      13 patients with intersex disorders and 18 patients with type 1 diabetes
      mellitus. Internal consistency was checked by Cronbach's alpha and test-retest
      reliability using intra-class correlation coefficient. Responses of 28 parents to
      a questionnaire on factors affecting the decision of sex of rearing were recorded
      on a 5-point Likert scale in order of importance. RESULTS: Cronbach's alpha was
      0.92 and 0.75, and intra-class correlation coefficient 0.76 and 0.75, for the
      gender role behavior and quality-of-life questionnaires respectively, indicating
      a high degree of internal consistency and stability. The mean composite scores
      for healthy girls on the gender role behavior questionnaire (82.5 +/- 8.7)
      differed significantly from that for healthy boys (53.2 +/- 7.1, p <0.001).
      Factors important to parents while making decisions for sex of rearing were
      appearance of the genitalia, medical advice, ability to bear children and
      economic independence. CONCLUSIONS: We have created valid tools to study gender
      role behavior and quality of life in adolescent patients with intersex disorders
      in India. We have also identified in a quantitative way the factors of greatest
      importance to parents while deciding sex of rearing. These results have direct
      utility in the management of patients with intersex disorders in India and other
      similar cultures.

PMID- 16995568
TI  - Prevalence of goitre and autoimmune thyroiditis in schoolchildren in Delhi,
      India, after two decades of salt iodisation.
AB  - Delhi lies in the sub-Himalayan plains and the existence of iodine deficiency is
      well established. Iodised salt was introduced in Delhi nearly two decades ago.
      The aim of the present study was to determine the status of iodine nutrition in
      school-aged children and the prevalence of autoimmune thyroiditis. A total of
      4,320 schoolchildren (2,218 [51.3%] boys) aged 10-16 years were studied. Goitre
      was detected in 396 children, an overall goitre prevalence of 9.2%. Of the 396
      children with goitre, 112 (28.3%) had evidence of autoimmune thyroiditis (AIT).
      The median urinary iodine (UI) excretion in the study population as a whole was
      14.6 microg/dl. The median UI in the group of children with goiter was 13.3
      microg/dl, whereas UI in children with goiter and evidence of AIT was 16.6
      microg/dl (p <0.01). Of the 112 children with AIT, 77 (68.7%) were euthyroid, 23
      (20.5%) had subclinical hypothyroidism, eight (7.2%) had hypothyroidism and the
      remaining four (3.6%) had hyperthyroidism. UI was high in goitrous children with
      AIT, and in children with thyroid dysfunction. Further studies are needed to
      clarify whether the higher UI in goitrous children with AIT is causally related
      to AIT or is due to the inability of the diseased thyroid to trap available
      iodine efficiently.

PMID- 16995569
TI  - Ovarian cysts in young girls with hypothyroidism: follow-up and effect of
      treatment.
AB  - Ovarian cysts have been reported in girls with longstanding uncompensated primary
      hypothyroidism. Restoration of euthyroid state has been associated with
      resolution of these cysts; long-term follow-up of these patients is however
      lacking. We evaluated the outcome in ten girls with ovarian cysts and
      hypothyroidism managed at our hospital with special emphasis on subsequent
      pubertal development and ovarian imaging. Patients were diagnosed at the age of
      8.6 +/- 2.3 years (mean +/- SD) with severe uncompensated primary hypothyroidism
      (TSH levels >100 mIU/l in all; 509.3 +/- 651 mIU/l) and growth retardation
      (height SDS -4.1 +/- 1.8). Nine girls had vaginal bleeding at diagnosis; five
      also had thelarche. LH and FSH levels were prepubertal in all patients. Ovarian
      cysts were bilateral in eight girls (80%); internal septation was noted in six.
      Thyroxine replacement (4.1 +/- 0.7 microg/kg/day) led to normalization of TSH
      levels with reversal of pubertal changes and regression of ovarian cysts in all
      patients 2.2 +/- 1.0 months after treatment. At last follow-up 3.5 +/- 2.6 years
      after initiation of treatment at the age of 12.0 +/- 2.3 years, all patients had
      normal ovarian size in ultrasound evaluation with six girls progressing to normal
      puberty. Our study emphasizes the need to exclude hypothyroidism in young girls
      with ovarian cysts. Identification of hypothyroidism in these girls obviates the
      need for extensive investigations.

PMID- 16995570
TI  - Estradiol levels and secretory dynamics in normal girls and boys as determined by
      an ultrasensitive bioassay: a 10 year experience.
AB  - We utilized an ultrasensitive recombinant cell bioassay to measure serum
      estradiol in 800 normal children from birth through puberty. 105 children had
      repeat samples every 4 months as they approached puberty. We measured estradiol
      levels every hour for 24 hours in 55 children. Estradiol increased with age and
      pubertal stage in girls and boys, and was higher in girls than boys at each
      stage. Prepubertal girls have estradiol levels of 1.6 +/- 2.6 pg/ml. Prepubertal
      boys have estradiol levels of 0.4 + 1.1 pg/ml. Estradiol had a diurnal variation
      in girls and boys, with the trough occurring 08.00-20.00 h in girls, and 12.00
      20.00 h in boys. We confirm that estradiol levels are higher in girls than boys
      even before physical signs of puberty, and that estradiol increases throughout
      puberty in girls and boys. This 10-year experience in 800 children shows the
      range and variability of estradiol by an ultrasensitive bioassay.

PMID- 16995571
TI  - Characterization of alterations in carbohydrate metabolism in children with
      Prader-Willi syndrome.
AB  - OBJECTIVE: To study carbohydrate metabolism and insulin sensitivity and secretion
      in children and adolescents with Prader-Willi syndrome (PWS) compared with
      multifactorial obesity (MO) controls. PATIENTS AND METHODS: Seventy-five patients
      with PWS and 395 controls with MO were studied by oral glucose tolerance test.
      Insulin resistance (IR) and beta-cell function were assessed by homeostasis model
      assessment (HOMA), insulin glucose index, fasting insulin and insulin sensitivity
      index. RESULTS: The incidence of diabetes mellitus was 0% in PWS and 1.5% in MO,
      while carbohydrate intolerance was 9.3% in the former group and 7.6% in the
      latter (NS); basal insulin level (12 +/- 8.2 vs 22.3 +/- 25 mU/ml) and HOMA-IR
      (2.47 +/- 1.6 vs 4.18 +/- 5.05) were lower in PWS (p = 0.004 and 0.04,
      respectively), whereas HOMA beta-cell index was lower in PWS than in MO (59 +/-
      42 vs 102 +/- 119, p = 0.03). ISI Composite was higher in PWS compared to MO (6
      +/- 5.7 vs 4.18 +/- 5.05, p = 0.04). CONCLUSION: Patients with PWS presented
      lower insulin resistance and a dissociation between beta-cell secretion and the
      degree of obesity.

PMID- 16995572
TI  - Use of subcutaneous DDAVP in infants with central diabetes insipidus.
AB  - Traditional methods for treating central diabetes insipidus during infancy, such
      as fluid therapy or the use of intranasal hormone replacement, have significant
      potential limitations. In a retrospective study of infants with diabetes
      insipidus, we examined outcome using subcutaneous (sc) DDAVP, and compared this
      to infants treated with intranasal lysine vasopressin or DDAVP. After in-patient
      dosage titration, outpatients' serum sodium concentrations were maintained in a
      narrower range in the sc group compared with the intranasal group, and the
      percentage of serum sodium concentrations within the normal range was greater in
      the sc group. There were no significant complications in either group. We
      conclude that DDAVP administered subcutaneously can be a safe and effective
      alternative to traditionally recommended treatments of central diabetes insipidus
      during infancy.

PMID- 16995573
TI  - Acute effects of hyperglycaemia in children with type 1 diabetes mellitus: the
      patient's perspective.
AB  - INTRODUCTION: This study presents the results of a systematic examination of how
      parents and patients perceive the effects of acute hyperglycaemia on mood and on
      intellectual and fine-motor performance. METHODS: A random sample of parents and
      children with type 1 diabetes mellitus (n = 380) were asked via questionnaire
      about their perception of the effects of hyperglycaemia. RESULTS: Answers were
      received from 368 children and parents (97%); mean age was 12.5 years (range 3.7
      to 19.8 years). Blood glucose levels between 15-18 mmol/l were reported by 68% to
      affect thinking performance, by 75% to affect mood and emotions and by 53% to
      affect coordination. The symptoms most commonly associated with hyperglycaemia
      were (in decreasing order): irritable (64%), short-tempered (60%), moody (56%),
      unreasonable (43%), aggressive (37%), hyperactive (31%), sad/depressed (27%)
      confused (23%), clumsy (18%). Homework was thought to be affected by
      hyperglycaemia in 36%, sport in 25%, play activity in 32%. Higher mean HbA1c
      since diagnosis was associated with higher reporting of effects on feeling/mood
      (p <0.001). Parents were especially concerned about the effects of hyperglycaemia
      on school and social interaction. CONCLUSIONS: The effects of hyperglycaemia on
      immediate performance are of concern to children and parents. Hyperglycaemia (15
      18 mmol/l) is reported to influence emotion and behaviour more than intellectual
      and fine-motor performance. This may contribute to the adverse psychological
      consequences of type 1 diabetes mellitus in children.

PMID- 16995574
TI  - Prevalence of retinopathy and microalbuminuria in pediatric type 2 diabetes
      mellitus.
AB  - BACKGROUND: There has been a dramatic rise of type 2 diabetes mellitus (DM2) in
      the US pediatric population, yet the presence of retinopathy and microalbuminuria
      in this cohort has not yet been described. AIM: To assess the presence of
      retinopathy and microalbuminuria in a cohort of predominantly minority
      adolescents (African American and Caribbean Hispanic) with DM2. PATIENTS AND
      METHODS: Forty pediatric patients with DM2 were examined between July, 2001 and
      June, 2003 for the presence of retinopathy. Data were also collected regarding
      microalbuminuria, body mass index, HbA1c, and family history of DM. RESULTS: Of
      the 40 patients examined, one patient (2.5%) had retinopathy, whereas nine
      (27.3%) had microalbuminuria. CONCLUSIONS: In young predominantly minority
      adolescents with DM2, retinopathy is rare, while microalbuminuria is common.

PMID- 16995575
TI  - Cardiac surgery unmasks latent hypoparathyroidism in a child with the 22q11.2
      deletion syndrome.
AB  - The 22q11.2 deletion syndrome is a developmental field defect of the third and
      fourth pharyngeal pouches characterized by a spectrum of thymic and parathyroid
      gland abnormalities and conotruncal cardiac defects. Latent hypoparathyroidism,
      defined as normocalcaemia at rest but reduced ability to secrete parathyroid
      hormone (PTH) in response to pharmacologically evoked hypocalcaemia, is found in
      30-50% of people with this syndrome. Its natural history is unknown. We describe
      a 1.5 year-old girl with tetralogy of Fallot, normal calcium metabolism and few
      facial dysmorphic features who developed transient hypoparathyroidism in the
      postoperative period, which lasted months and waxed and waned during this
      observation period. The clinical picture led us to the diagnosis of 22q11.2
      deletion syndrome.

PMID- 16995576
TI  - Juvenile fibrocalculous pancreatopathy--a patient report.
AB  - Fibrocalculous pancreatopathy (FCPP) is a secondary form of diabetes mellitus
      (DM) with obscure etiology. Recently various gene mutations have been reported in
      patients with FCPP from the Indian subcontinent. Initially termed tropical
      pancreatic diabetes, FCPP is uncommon and is characterized by pancreatic
      calcifications. The diagnosis is made in the third decade of life in most
      patients with the onset of abdominal pain and DM. We report a female child with
      DM diagnosed at the age of 3 years who had been managed with insulin but was
      ketosis resistant. The diagnosis of FCPP was made 3 years later. There were no
      mutations at N34S and P55S in the SPINK1 gene.

PMID- 16995577
TI  - Dopaminergic resistant prolactinomas in the peripubertal population.
AB  - We report two children with macroadenomas and hyperprolactinemia resistant to
      medical therapy using dopamine agonists, who experienced secondary pituitary
      dysfunction. Both required surgical debulking, and one has received growth
      hormone treatment with no increase in tumor size.

PMID- 16995578
TI  - Central and gonadal hypogonadism in X-linked lissencephaly.
AB  - OBJECTIVE: To directly test gonadal function in a patient with X-linked
      lissencephaly with ambiguous genitalia (XLAG) in light of lack of previous
      functional data. STUDY DESIGN AND RESULTS: We studied an infant who failed to
      increase testosterone levels in response to hCG stimulation. CONCLUSION: In XLAG,
      the gonads are not only structurally dysgenetic but also functionally abnormal.

PMID- 16995579
TI  - Do we need to build a different "better mousetrap"?

PMID- 16995580
TI  - Treatment of central precocious puberty with triptorelin 11.25 mg depot
      formulation.
AB  - A new triptorelin 11.25 mg long depot formulation is now available for the
      treatment of central precocious puberty (CPP). The aim of our study was to
      evaluate the efficacy of triptorelin 11.25 mg administered every 90 days to
      suppress gonadotropin and sex steroid secretion and pubertal signs in children
      with CPP during 2 years of treatment. Inclusion criteria were clinical pubertal
      development before the age of 8 years in girls or 9 years in boys, advanced bone
      age and a pubertal LH response (peak >5 mIU/ml) to GnRH. We studied 20 patients
      (19 girls and 1 boy), with a median age at entry into the study of 7.5 +/- 0.2
      years for girls, and 9 years for the boy. The basal and GnRH-stimulated serum
      levels of LH and FSH decreased significantly from baseline to 3 months of therapy
      (p <0.0001). All patients had a GnRH-stimulated peak below 3 mIU/ml between 6 and
      24 months of treatment. The pituitary-gonadal axis recovered adequately after
      discontinuation of therapy. These results suggest that 3-month depot triptorelin
      is a satisfactory alternative for the therapy of children with CPP. The longer
      interval between injections may increase acceptability and compliance with
      treatment.

PMID- 16995581
TI  - Impact of body mass index on growth in boys with delayed puberty.
AB  - It is unclear whether overweight but otherwise healthy boys with delayed puberty
      have a variation of constitutional delay of growth and maturation (CDGM) or a
      different etiology for their pubertal delay. To characterize better this group of
      boys and investigate whether their growth pattern distinguishes them from boys
      with typical CDGM, growth data were analyzed in eight overweight (BMI SDS > or =
      85th percentile) and 37 non-overweight (BMI SDS <85th percentile) boys with
      delayed puberty. Primary outcome measures included predicted height (PH) and
      adult height (AH). At diagnosis of delayed puberty, the overweight boys had less
      delayed bone ages (chronological age [CA] - bone age [BA] = 1.2 +/- 1.0 vs 2.5 +/
      1.1 years, p <0.01), greater height SDS for CA (-0.5 +/- 0.7 vs -2.4 +/- 0.8, p
      <0.001), and greater height SDS for BA (0.6 +/- 0.9 vs -0.4 +/- 1.1, p <0.05). PH
      for the overweight boys exceeded their mid-parental height (MPH) by 5.0 +/- 7.2
      cm while non-overweight boys were predicted to fall below their MPH by 2.8 +/-
      6.3 cm (p <0.01). Available AH data corroborated the differences in PH, with a
      trend for overweight boys to have greater height relative to their MPH than the
      non-overweight boys. These observations suggest that in the context of delayed
      puberty, being overweight may modulate adult height and/or that the etiology of
      delayed puberty in overweight boys may differ from typical CDGM.

PMID- 16995582
TI  - The relationships between dental age, chronological age and bone age in Turkish
      adolescents with constitutional delay of growth.
AB  - The aim of this study was to investigate the relationships between dental age and
      bone age in Turkish adolescents with constitutional delay of growth and compare
      them with a group of normal, healthy adolescents. Left hand and wrist radiographs
      and dental panaromic radiographs of 33 adolescents (25 boys and 8 girls) aged
      between 10 and 16 years with constitutionally delayed growth were assessed. The
      control group comprised 41 healthy adolescents (24 boys, 17 girls) aged between
      10 and 16 years. Bone age was determined according to Greulich and Pyle; dental
      age was assessed using the Demirjian method. In the control group, no statistical
      difference was found between chronological, bone and dental ages. In the group of
      adolescents with constitutional growth delay, there was no significant difference
      between chronological age and dental age, but the differences between dental age
      and bone age and between chronological age and bone age were found to be
      statistically significant. It was found that Demirjian's dental age assessment is
      a valid method for scoring dental age in Turkish adolescents. Adolescents with
      constitutional delay of growth had dental maturation appropriate for
      chronological age, but not for bone age.

PMID- 16995583
TI  - Pubertal height gain in Ullrich-Turner syndrome.
AB  - Short stature and ovarian failure are the main features in Ullrich-Turner
      syndrome (UTS). The aim of this retrospective analysis was to evaluate the
      influence of age at initiation of puberty on final height. Sixty-five girls were
      treated with growth hormone (GH) and had a final height of 150.6 +/- 5.7 cm;
      12/65 entered puberty spontaneously. A non-GH treated group of 12 girls with UTS
      reached a final height of 147.3 +/- 6.6 cm. Subdividing the GH treated group (n =
      53) based on the age at induction of puberty, before or after 13 years, there was
      no significant difference in final height. Final height was affected by the age
      at which GH treatment was initiated, height SDS at the beginning of puberty, and
      by the duration of GH therapy. Therefore, early treatment with GH for short
      stature in UTS should be attempted so that an age adequate initiation of puberty
      will be feasible.

PMID- 16995584
TI  - Oxidative stress markers in plasma and urine of prepubertal patients with type 1
      diabetes mellitus.
AB  - Markers of oxidative stress were studied in plasma and urine of prepubertal
      patients with type 1 diabetes mellitus (DM1) with less than 5 years of disease (n
      = 27). The results were compared to healthy, age- and sex-matched control
      children (n = 27). Oxidative stress parameters evaluated included advanced
      oxidation protein products (AOPP), total peroxyl radical-trapping antioxidant
      parameter (TRAP), and F2-isoprostanes (8-epi-prostaglandin-F2: 8-isoPGF2alpha).
      No statistically significant differences were found for any of the oxidative
      stress markers assessed between patients with DM1 and controls. In addition,
      weight, height, and routine metabolic tests, including creatininemia and
      cholesterol levels, were similar between the groups. The lack of significant
      differences between healthy controls and patients with DM1 suggests that
      treatment is able to counteract the increase in free radical production.

PMID- 16995585
TI  - Clinical characteristics and diabetes associated autoantibodies in patients with
      both type 1 diabetes mellitus and asthma.
AB  - OBJECTIVE: Type 1 diabetes mellitus (DM1) and asthma are mediated by opposite
      arms of the cellular immune system, namely T helper (Th)1 and Th2 CD4+ cells,
      respectively. It is not known whether their coexistence affects their clinical
      manifestations. METHODS: The number of asthma exacerbations, frequency of
      hypoglycemic events, HbA1c levels, diabetes associated autoantibody status and
      diabetes associated late complications were determined in three paired groups of
      patients (n = 11) matched by gender and age: DM1 and asthma, asthma only, and DM1
      only. RESULTS: Patients with both diseases had a higher prevalence of
      hypoglycemic events per month compared to patients with DM1 only: 5.67 +/- 4.27
      vs 1.45 +/- 2.06, respectively (p = 0.008). The co-existence of the two diseases
      did not modify the remaining clinical and laboratory parameters. CONCLUSION:
      Patients with both DM1 and asthma have similar clinical characteristics to
      patients with only one of these diseases apart from a higher rate of hypoglycemic
      events compared to patients with DM1 without asthma.

PMID- 16995586
TI  - The effect of obesity on echocardiographic and metabolic parameters in childhood.
AB  - BACKGROUND: Obese children are predisposed to left ventricular (LV) hypertrophy
      and cardiac dysfunction. We evaluated ventricular function of obese children with
      conventional echocardiography and tissue Doppler imaging (TDI) and correlated
      these with fasting serum glucose, lipid and insulin levels. METHODS: Thirty obese
      children were examined by conventional echocardiography and TDI and compared with
      an age-matched control group. In the obese children, fasting serum glucose,
      lipid, and insulin levels were obtained. RESULTS: Systolic and diastolic function
      of the LV was normal in obese children. LVM/ht2.7 (LVM normalized for height),
      relative wall thickness (RWT), and LV end-diastolic diameter were significantly
      greater in obese children. The early to late relaxation velocity ratio (E/A)
      determined by TDI for the right ventricle and interventricular septum (IVS) were
      significantly lower in the obese group, LVM/ht2.7 and RWT correlated with body
      mass index (BMI). In the obese group, IVS and LV posterior wall thickness
      correlated with insulin, very low density lipoprotein, and triglyceride levels.
      However, we failed to show this correlation when these measurements were indexed
      to height. CONCLUSION: Left ventricular hypertrophy, as evidenced by increased LV
      mass, was present in obese children. Higher BMI, insulin, very low density
      lipoprotein, and triglyceride levels were associated with LV hypertrophy. TDI
      revealed subclinical changes in diastolic function of the right ventricle and
      IVS.

PMID- 16995587
TI  - Evaluation of hypothalamic-pituitary-adrenal axis suppression by low-dose (0.5
      microg) and standard-dose (250 microg) adrenocorticotropic hormone (ACTH) tests
      in asthmatic children treated with inhaled corticosteroid.
AB  - The aim of this study was to compare the results of low-dose (LDT) and standard
      dose (SDT) ACTH tests in the assessment of adrenal function in 30 asthmatic
      children (mean age 9.35 +/- 1.9 years, 19 boys) who were treated with budesonide
      Turbohaler at conventional 400 microg or 600 microg daily doses for 8 weeks by a
      prospective, randomized, and open parallel study. Budesonide did not lead to any
      significant suppression of the hypothalamic-pituitary-adrenal (HPA) axis in
      either treatment group. However, when individual patient values were examined at
      the end point, peak cortisol concentrations after LDT were below 2 SDs of the
      pretreatment values in four patients (13.3%). Also, the increment in cortisol
      values was <200 nmol/l in all four patients. Decreased 24-hour urinary free
      cortisol excretion provided further evidence for HPA axis suppression in these
      patients. Two of these four poor responders to LDT showed normal stimulation with
      SDT. In conclusion, even with moderate doses and short-term use, adrenal
      suppression may occur in certain susceptible patients. The low-dose ACTH test is
      more reliable than SDT for the evaluation of such patients.

PMID- 16995588
TI  - Prevalence of hypovitaminosis D in early infantile hypocalcemia.
AB  - AIM: To further define the pathogenesis of infantile hypocalcemia, the prevailing
      vitamin D status, and treatment outcomes. METHODS AND RESULTS: Of the 23 infants
      admitted with infantile hypocalcemia, 21 had biochemical evidence of hypocalcemia
      and hyperphosphatemia and the other two had isolated hypocalcemia. The majority
      of these infants had relatively low serum intact parathyroid hormone responses
      against the backdrop of hypocalcemia. Thirteen (56.5%) of these infants had low
      25-hydroxyvitamin D (25-OHD) levels, of whom 69% were Hispanic and 23% were
      African American. Infantile serum vitamin D status reflected that of the mother
      in all the 16 instances in which it was measured. Treatment with calcitriol
      hastened recovery from hypocalcemia in our series. CONCLUSIONS: Relative
      hypoparathyroidism is the etiology in the majority of cases of late onset and
      early infantile hypocalcemia. We identified vitamin D deficiency in a significant
      percentage of infants with hypocalcemia, especially Hispanics and African
      Americans. Maternal 25-OHD concentrations should be ascertained if the infant has
      low 25-OHD levels.

PMID- 16995589
TI  - Intermittent growth attenuation: is this a sign of craniopharyngioma?
AB  - We present two young children eventually diagnosed with large craniopharyngiomas,
      who had a normal growth velocity for several years following an initial short
      period of growth attenuation. These cases suggest the need for a low threshold to
      undertake hormonal evaluation of patients who present with a past history of
      growth attenuation.

PMID- 16995590
TI  - Muscle infarction in a 13 year-old female with type 1 diabetes mellitus of short
      duration.
AB  - A 13 year-old female with an 11-month history of type 1 diabetes mellitus (DM)
      was admitted to the hospital with a muscle infarction. Diagnosis of this rare
      complication of DM was suggested by clinical presentation, magnetic resonance
      imaging (MRI) and muscle biopsy. While diabetic muscle infarction (DMI) has been
      previously described in adult patients with long-standing DM associated with
      microangiopathy, it is an unexpected finding in this clinical setting.

PMID- 16995591
TI  - Type 1 diabetes mellitus associated with nephrotic syndrome.
AB  - Nephrotic syndrome (NS) in a patient with diabetes mellitus (DM) first suggests
      the diagnosis of diabetic nephropathy. However, glomerular diseases other than
      diabetic nephropathy have been reported in patients with DM. We present a child
      with type 1 DM (DM1) associated with NS. A 3 year-old boy who was diagnosed with
      DM1 developed proteinuria in nephrotic range at the 10th month of follow-up. He
      had remission on steroid treatment without any problem in glycemic control as he
      was given tapered daily doses instead of an alternate day regimen. He relapsed at
      the 7th month of follow-up, and cyclophosphamide treatment brought about
      remission. He had HLA A24, DR4 and DR53 antigens in common with previously
      reported cases of DM-NS association. The immunological basis of these diseases
      may have a causal effect on the association, but the etiopathogenesis is still
      unclear.

PMID- 16995592
TI  - Pseudohypoparathyroidism type 1a with congenital hypothyroidism.
AB  - Pseudohypoparathyroidism type la (PHP-1a) is an uncommon disorder that results
      from an inactivating mutation in the GNAS gene. It can present with resistance to
      several hormones, in addition to parathyroid hormone (PTH). Patients may have the
      classic Albright's hereditary osteodystrophy (AHO) phenotype and can develop
      resistance to thyroid stimulating hormone (TSH), gonadotropins, growth hormone
      releasing hormone (GHRH), and other hormones that rely on the Gsalpha protein to
      regulate signal transmission at their receptors. We report two siblings with PHP
      1a and congenital hypothyroidism. The patients were found to have a heterozygous
      mutation at nucleotide 305 in exon 4 (c305C-->A) of the GNAS gene, which has not
      been previously linked to congenital hypothyroidism.

PMID- 16995593
TI  - A new therapeutic indication of botulinum toxins: sialorrhea.

PMID- 16995594
TI  - Study of behavioral and psychological symptoms of dementia in Taiwan.
AB  - The behavioral and psychological symptoms of dementia (BPSD) are common serious
      problems that affect the quality of life for both the patients with such symptoms
      as well as their caregivers. BPSD present a major challenge in the medical
      management of patients and are the major cause of institutionalization.
      Alzheimer's Disease (AD) is the most common type of dementia in Taiwan. I
      performed a systematic literature review on BPSD studies and found that Taiwanese
      patients with AD exhibit many of the BPSD. Studies showed that between 30% and
      63% of Taiwan's AD patients experienced delusion. Hallucination occurred less
      frequently, which ranged from 21% to 26%. Anxiety occurred in 35-76% of patients
      and depression 22-50%, sleep abnormalities 26-61% and 39-46%. The differences in
      the prevalence of BPSD might result from the different clinical settings and
      evaluation instruments. The prevalence and clinical manifestations of BPSD in
      Taiwan are similar to Western reports and it suggests that most of BPSD are
      neurobiologically determined. Based on differing cultural backgrounds, the
      interpretation of agitation and apathy might differ, so, the development of cross
      cultural applicable criteria and rating scales for the assessment and treatment
      of BPSD are important for future studies.

PMID- 16995595
TI  - Genetic characteristics of dementia in Taiwan.
AB  - The most common causes of dementia in Taiwan are Alzheimer's disease (AD)
      followed by vascular dementia (VaD). Several genetic studies have documented an
      increased risk of AD among apolipoprotein E gene allele 4 (ApoE4) carriers in
      Taiwanese (ethnic Chinese). Although ApoE4 is considered the most important risk
      factor for AD, the ApoE4 allele frequency is lower in Taiwanese (around 7%), than
      that in most Caucasian populations (over 10%). This phenomenon raises the
      hypothesis that low ApoE4 allele frequency contributes to the low prevalence of
      AD in Taiwanese. Other studies of the genetic impacts on modulation or regulation
      of manifestations, progression, and treatment response of AD in Taiwan have been
      inconclusive. Familial AD, which is conferred by PS1 gene mutation has been
      identified. There were very few studies of fronto-temporal dementia (FTD) or
      dementia with Lewy body (DLB) in Taiwan. Genetic studies of VaD remain limited
      and only NOTCH3 gene mutation has been detected in a Taiwanese cerebral autosomal
      dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL)
      family. Limited data indicated that non- ApoE4-associated AD may represent a
      larger proportion of AD in Taiwanese, suggesting the existence of novel genetic
      factors which remain to be identified.

PMID- 16995596
TI  - Botulinum toxin type A treatment for Parkinsonian patients with moderate to
      severe sialorrhea.
AB  - PURPOSE: To investigate the effect of botulinum toxin type A (BTX-A; Botox) in
      reducing saliva in patients with Parkinsonism. METHODS: Fifteen patients with
      clinical diagnosis of idiopathic Parkinson's disease, dementia with Lewy bodies,
      or multiple system atrophy were enrolled in this open clinical trial. A total of
      40-unit dose of Botox was injected into the bilateral parotid and submandibular
      glands. Objective measuring of saliva production with dental rods, subjective
      Drooling Score, personal impression of clinical improvement, and the duration of
      response were used for the global assessment of sialorrhea after BTX-A treatment.
      RESULTS: All patients showed objective reduction in saliva production following
      BTX-A treatment and the mean production was reduced at a significant level. The
      severity of sialorrhea assessed by Drooling Score was 5.87 +/- 0.92 (range: 5-8)
      and 3.60 +/- 1.18 (range: 2-6) respectively (p<0.001) before and after BTX-A
      injection. The mean duration of BTX-A response extended for 16.3 +/- 5.7 weeks
      (range: 5-24). No severe adverse effect nor worsening of existing dysphagia was
      observed in all Parkinsonian patients. CONCLUSIONS: Parkinsonian drooling may
      undermine patient's health and daily activity. BTX-A local injection is a safe
      and effective measure in counteracting sialorrhea, even in patients associated
      with moderate dysphagia.

PMID- 16995597
TI  - Temporal patterns of body temperatures in the acute stage of stroke.
AB  - OBJECTIVE: The present study aimed to describe the day-by-day temporal patterns
      of body temperatures in acute stroke and to delineate the differences in serial
      daily changes in body temperatures between intracerebral hemorrhage (ICH) and
      cerebral infarct (CI). METHODS: We retrospectively enrolled 90 patients (32 with
      ICH and 58 with CI), admitted within 12 hours after the onset of stroke. Body
      temperatures were measured as the tympanic temperatures during the initial 6 days
      of hospitalization. Patients with clinical infections were excluded. The severity
      of stroke was assessed by Scandinavian Stroke Scale (SSS). SSS score < or = 30
      was defined as severe stroke, and SSS score >30 as mild-to-moderate stroke.
      RESULTS: Mean body temperature was significantly higher in patients with ICH than
      those with CI in 0 approximately 12 hours; 12 approximately 24 hours, 24
      approximately 48 hours, and 48 approximately 72 hours (all p<0.05) after the
      onset of stroke. Among patients with ICH, the body temperature was significantly
      higher in the severe group than the mild-to-moderate group during 24
      approximately 48 hours and 48 approximately 72 hours (both p<0.05) after the
      onset of stroke. No significant difference in body temperatures was observed
      between patients with severe stroke and patient with mild-to-moderate CI.
      CONCLUSIONS: The serial time course of body temperature in the acute stage of
      stroke differs between ICH and CI. This study showed that, in ICH but not in CI,
      the elevation of body temperature has significant association with the stroke
      severity. Our results may help in the management of hyperthermia during acute
      stroke.

PMID- 16995598
TI  - Contact heat evoked potentials in normal subjects.
AB  - Laser-evoked potentials are widely used to investigate nociceptive pathways. The
      newly developed contact heat stimulator for evoking brain response has the
      advantages of obtaining reliable scalp potentials and absence of cutaneous
      lesions. This study aimed to identify the most appropriate stimulation site with
      consistent cortical responses, and to correlate several parameters of the contact
      heat evoked potentials (CHEPs) with age, gender, and body height in normal
      subjects. CHEPs were recorded at Cz with a contact heat stimulator (Medoc,
      Israel) in 35 normal controls. The subjects were asked to keep eyes open and
      remain alert. The baseline temperature was 32 degrees C, and stimulation peak
      heat intensity of 51 degrees C was applied to five body sites: bilateral forearm,
      right dorsum hand, right peroneal area, and right dorsum foot. Reproducible CHEPs
      were recorded more frequently when stimulated at volar forearm (62.5%) than at
      the lower limbs (around 40%). The first negative peak latency (N1) was 370.1 +/-
      20.3 ms, first positive peak latency (P1) was 502.4 +/- 33.0 ms, and peak to peak
      amplitude was 10.2 +/- 4.9 microV with stimulation of the forearm. Perceived pain
      intensity was not correlated with the presence or amplitude of CHEPs. No gender
      or inter-side differences were observed for N1 latency and N1-P1 amplitude. Also,
      no correlation was noted between N1 and age or body height. These results support
      future clinical access of CHEPs as a diagnostic tool.

PMID- 16995599
TI  - Central vasomotor failure in a patient with medulla arteriovenous fistula.
AB  - We report on the case of a 60-year-old man who suffered from hiccup, dysphagia
      and unsteady gait for three months. He was diagnosed with intracranial dural
      arteriovenous fistula in medulla with retrograde perimedullary vein drainage. He
      developed quadriplegia, persistent shock status and symptomatic bradycardia
      immediately after a conventional cerebral angiography study. After excluding
      cardiogenic, hypovolemic, anaphylactic and septic shock, central vasomotor
      failure caused by venous thrombosis of the lesion was considered. The patient's
      central vasomotor failure recovered after continuous dopamine infusion treatment
      for 42 days. We concluded that venous hypertension with venous thrombosis in
      rostral ventrolateral medulla (RVLM), a major vasomotor center in the brainstem,
      was the lesion site. In our case, vasomotor dysfunction caused by an RVLM lesion
      related to venous thrombosis is considered as causative.

PMID- 16995600
TI  - Hypothyroidism and cerebral infarction: a case report and literature review.
AB  - Thyroid hormone has been studied in cardiovascular disease but rarely in
      cerebrovascular disease (CVD). Recently, hypothyroidism has been suggested to be
      related to risk factors such as atherosclerosis but not directly to CVD. We
      reported a 52-year-old woman with acute ischemic stroke, and greatly improved
      general conditions after thyroid hormone replacement. Hypothyroidism is reported
      to be one of the causes of hypertension or elevated cholesterol levels, the
      established risk factors of CVD. Further studies of the possible association of
      thyroid hormone and CVD are warranted. Thyroid hormone might need to be surveyed
      in CVD patients especially if there are symptoms and signs of thyroid disorders.

PMID- 16995601
TI  - Young stroke, cardiac myxoma, and multiple emboli: a case report and literature
      review.
AB  - Cardiac myxoma is a source of emboli to the vascular tree, especially to the
      central nervous system. Although it is rare, its early recognition is
      particularly important because of its unique clinical features of subsequently
      leading to intracerebral or subarachnoid hemorrhage, even brain metastases, and
      its potential for surgical cure. Missing the diagnosis may lead to devastating
      results, including stroke, even sudden death. A 40-year-old male with no other
      conventional vascular risk factors such as hypertension, diabetes or
      hyperlipidemia presented with right hemiplegia, global aphasia, vomiting, and
      fever. Infarction over the left middle cerebral artery was disclosed on magnetic
      resonance imaging study, and echocardiogram showed a huge mass, about 5cm in
      size, on the mitral valve which was histopathologically proved to be a cardiac
      myxoma. He also presented with multiple emboli to the kidneys and the left eye.
      There is uncertainty about the role of anticoagulation. The treatment of choice
      remains surgical excision of the cardiac myxoma which may lead to normalization
      of serum interleukin-6 levels and resolution of constitutional symptoms, and the
      intracranial aneurysms may regress and resolve.

PMID- 16995602
TI  - [Electrophysiology of subthalamic nucleus in normal and Parkinson's disease].
AB  - Subthalamic nucleus (STN) has been known to play an important role in the
      regulation of cortico-basal ganglia-thalamo-cortical loop. STN neurons have
      pacemaking activitiy and their firing pattern can switch from spike mode to
      bursting mode when membrane potential becomes hyperpolarized. Recent study has
      shown that STN neurons show marked increase in burst and oscillatory activity
      during the dopamine-depleting state of Parkinson's disease (PD). This
      electrophysiological change in activity is now considered as an characterstic
      pathophysiological feature of PD. High frequency stimulation of STN can modify
      and "normalize" the activity of STN neurons in the pathophysiologial state. This
      electrophysiological treatment applied to STN, known as deep brain stimulation
      (DBS) clinically, ameliorates the symptoms of PD effectively, and is becoming a
      standard treatment in patients with advanced PD. This article would review the
      basic researches concerning electrical activities of STN and try to extend the
      basic knowledge into clinical applications.

PMID- 16995603
TI  - [Centennial of the nobel prize for Golgi and Cajal--founding of modern
      neuroscience and irony of discovery].
AB  - In 1906, Golgi and Ramon y Cajal shared the Nobel Prize in Physiology or Medicine
      "in recognition of their work on the structure of the nervous system". However,
      it was an unusual occasion in the history of Nobel Prize award because their
      views on the structure of the nervous system were not only different but even
      opposite, creating the "storm center of histological controversy". Furthermore,
      the new staining method Cajal had employed to study the nervous system was
      developed by Golgi, creating an irony of discovery. In 1873, Golgi revolutionized
      the histological study of the nervous system by developing a new staining method,
      "la reazione nera" or black reaction, which allowed good visualization of axons,
      dendrites and glia. But because his stain was so selective, staining only about 3
      percent of neurons, he was unable to see clearly how the neuronal processes ended
      as they approached other neurons. Consequently, he embraced the popular belief
      that neuronal processes physically fuse with each other--the "reticular theory".
      On the other hand, Cajal was incidentally introduced to the Golgi stain 14 years
      after its discovery and immediately realized its beauty. He found that better
      results could be produced by staining more intensely and cutting thicker
      sections. He further observed that the Golgi stain worked best on non-myelinated
      axons. The search for brains containing non-myelinated axons led him to study
      birds and very young mammals, including embryos. Cajal obtained fascinating
      results by modifying the Golgi stain and by studying avian and young mammalian
      brains. From those studies, Cajal was able to infer that axons and dendrites
      ended freely and did not physically anastomose. Therefore, he strongly advocated
      the "neuron theory". Golgi seemed to be too headstrong and too conservative to
      relinquish his belief that neurons constitute a network which reacts as a whole.
      On the other hand, Cajal's hard work using the Golgi stain led to new
      understanding on the structure and function of the nervous system, and earned him
      "the founder of modern neuroscience". This centennial occasion may be further
      impressed by Cajal's comment on the shared Nobel Prize that "what a cruel irony
      of fate of pair, like Siamese twins united by the shoulders, scientific
      adversaries of such contrasting character!".

PMID- 16995604
TI  - Skin manifestation and pathological changes in dermatomyositis.

PMID- 16995605
TI  - Easy evaluation of research in evidence-based dentistry.

PMID- 16995606
TI  - Informed consent not so controversial in California.

PMID- 16995607
TI  - Preventing dental disease.

PMID- 16995608
TI  - Not following the law can cause big trouble.

PMID- 16995609
TI  - Evidence-based dentistry: a clinician's perspective.
AB  - Evidence-based dentistry is a discipline that provides best, explicit-based
      evidence to dentists and their patients in shared decision-making. Currently,
      dentists are being trained and directed to adopt the role of translational
      researchers in developing evidence-based dental practices. Practically, evidence
      based dentistry is not usable in its current mode for the provision of labor
      intensive services that characterize current dental practice. The purpose of this
      article is to introduce a model of evidence-based dental practice. This model
      conceptualizes a team approach in explaining problems and solutions to change
      current dental practice. These changes constitute an evidence-based dental
      practice that involves the electronic chart, centralized database, knowledge
      management software, and personnel in optimizing effective oral health care to
      dental patients.

PMID- 16995610
TI  - Making clinical decisions using a clinical practice guideline.
AB  - Clinical practice guidelines are statements developed from best evidence about
      clinically relevant appropriate care. A simulated patient case is presented to
      demonstrate how to use a CPG in decision-making in determining a clinical
      decision. Conceptualized knowledge management software templates are provided to
      explain a process by which best evidence is retrieved from a primary, centralized
      network database. Templates describe the process of converting a clinical
      question into a research question, retrieving best evidence, and performing data
      analysis for the outcome of individualizing and optimizing a clinical decision.
      Templates also describe the reciprocation of information to update CPGs by
      translational researchers who manage and build the primary, centralized network
      database.

PMID- 16995611
TI  - The translational clinical practice system: a way to implement the evidence-based
      approach in the dental office.
AB  - Evidence-based decision-making in dental practice is challenging and rewarding.
      But for many clinicians, the evidence-based approach is an abstract and even
      theoretical idea that sounds good, but is not very practical. The Translational
      Clinical Practice System provides an overriding domain and a system within which
      the evidence-based approach may be more effectively utilized in clinical
      practice. Most would agree that using good evidence, information, and data as the
      basis for decisions are the starting points toward reaching the best results for
      the patient. However, there are clearly insufficiencies in the currently
      available best scientific evidence for many of the procedures patients need. The
      good news is that the evidence environment is improving and better quality
      information is becoming available in the office where it is needed. This article
      describes a logical and straightforward approach for clinicians to use in order
      to put together complex and often interwoven factors involved with patient care.
      Specific clinical examples are provided.

PMID- 16995612
TI  - Evidence-based recommendations for the use of sealants.
AB  - In traditional research, the "level of significance" refers to the probability
      value used to reject the null hypothesis. In evidence-based research, a similar
      term, "the level of evidence" refers to the quality of the published report that
      is analyzed critically in the context of a systematic review. A systematic
      review, the principal research tool of evidence-based dentistry, is distinct from
      a classical narrative literature review in that it is focused to examine the
      strengths and weaknesses of the research methodology, design and data analysis of
      each report included in the review. A systematic review is very clearly defined,
      and sets out to find what evidence there is for prescribing a particular
      intervention for a given patient. Evidence-based recommendations are grounded on
      systematic reviews, and the evaluation of systematic reviews in a given domain of
      dentistry is critical for the successful implementation of evidence-based dental
      practice. In the context of sealants, the evidence indicates that the
      intervention is effective in preventing dental decay on the molars and premolars
      of susceptible children and adolescents (Level of evidence: II-1). The preventive
      effect for second-generation sealants ranges from 33 percent to 71 percent. The
      median preventive effect is higher when sealants are reapplied, compared to a
      single application, because sealant effectiveness decreases over time. The
      majority of studies have focused on molars, and fewer studies have examined the
      preventive effect of sealants on premolars. In this paper, the authors have
      developed evidence-based recommendations for the use of sealants by discussing
      the level of evidence and, when applicable, the number needed to treat (NNT) and
      the prevented fraction (PF), two fundamental criteria in evidence-based dental
      practice.

PMID- 16995613
TI  - Interspecific hybridization in ants: at the intersection of ecology, evolution,
      and behavior.
AB  - Ants are social and are haplodiploid. This combination may allow the evolution of
      a variety of unusual genetic pathways to achieve reproductive success. These
      include hybridizing across species, differential use of sperm to create a hybrid
      worker population, and reproductively isolated gene pools that depend on each
      other for their survival. Although there are demonstrable costs for colony
      development and reproduction, these phenomena may nevertheless be relatively
      common in nature. The specific ecological advantages that favor the evolution of
      these reproductive modes remain to be discovered.

PMID- 16995614
TI  - Sperm parasitism in ants: selection for interspecific mating and hybridization.
AB  - Interspecific mating in eusocial Hymenoptera can be favored under certain
      conditions even if all hybrid offspring are completely infertile. This exploits
      two key features of the eusocial Hymenoptera: a haplodiploid genetic system and
      reproductive division of labor in females. Interspecifically mated queens can
      still produce viable sons that will mate intraspecifically. Apparent reduced
      fitness resulting from producing infertile daughter gynes can be also offset by
      advantages conferred by hybrid workers. An important advantage is likely to be
      superior ability at using marginal habitats. Interspecifically mated queens can
      nest in sites where intraspecific competition will be low. By mating
      interspecifically, a queen trades expected reproductive success through female
      offspring for a higher probability of achieving some reproductive success.
      Females that mate interspecifically can be considered "sperm parasites" on the
      males of the other species. I provide evidence that sperm parasitism is
      responsible for widespread hybridization in North America among two species of
      the ant subgenus Acanthomyops (genus Lasius), and review evidence for sperm
      parasitism in other hybridization phenomena in ants. Sperm parasitism in ants
      represents a novel form of social parasitism in ants and a dispersal
      polymorphism. It may also act as a precursor to the evolution of some other
      recently discovered phenomena, such as genetic caste determination.

PMID- 16995615
TI  - Reproductive isolation between Pogonomyrmex rugosus and two lineages with genetic
      caste determination.
AB  - Hybrid speciation occurs when combination of two interspecific genomes results in
      individuals that are of high fitness but reproductively incompatible with the
      parental species. Although hybrid speciation is a relatively common source of new
      species in plants, it appears to be a much rarer occurrence in animal taxa. Here
      we report on reproductive isolation and range overlap between the rough harvester
      ant Pogonomyrmex rugosus and two lineages with hybrid genotypes (H 1 and H2).
      Both lineages obligately interbreed and produce genetically distinct queen and
      worker offspring, a phenomenon referred to as genetic caste determination (GCD).
      Diploid offspring produced by gametes of the same lineage develop only into
      queens, whereas diploid offspring derived from gametes of distinct lineages
      develop into workers. We investigated small-scale patterns of gene flow between
      the parent and the two H lineages by sampling along an 80-km transect between a
      pure P. rugosus population and a two-lineage population. Microsatellite and
      mitochondrial markers both indicated virtually no gene flow between the parent
      species and either lineage even at sites where parental and H-lineage colonies co
      occurred. The geographic ranges of the parental species and the two-lineage
      population were essentially parapatric, with a surprisingly narrow band of
      overlap and evidence of spatial structuring even at microgeographic scales within
      the transition zone. This suggests that ecological competition with the parent
      species plays a significant role in determining the evolutionary persistence and
      current distribution of the hybrid lineages and the genetic caste system.

PMID- 16995616
TI  - Distribution and evolution of genetic caste determination in Pogonomyrmex seed
      harvester ants.
AB  - We examined the distribution and ancestral relationships of genetic caste
      determination (GCD) in 46 populations of the seed-harvester ants Pogonomyrmex
      barbatus and P. rugosus across the east-to-west range of their distributions.
      Using a mtDNA sequence and two nuclear markers diagnostic for GCD, we
      distinguished three classes of population phenotypes: those with GCD, no evidence
      of GCD, and mixed (both GCD and non-GCD colonies present). The GCD phenotype was
      geographically widespread across the range of both morphospecies, occurring in 20
      of 46 sampled populations. Molecular data suggest three reproductively isolated
      and cryptic lineages within each morphospecies, and no present hybridization.
      Mapping the GCD phenotype onto a mtDNA phylogeny indicates that GCD in P. rugosus
      was acquired from P. barbatus, suggesting that interspecific hybridization may
      not be the causal agent of GCD, but may simply provide an avenue for GCD to
      spread from one species (or subspecies) to another. We hypothesize that the
      origin of GCD involved a genetic mutation with a major effect on caste
      determination. This mutation generates genetic conflict and results in the
      partitioning and maintenance of distinct allele (or gene set) combinations that
      confer differences in developmental caste fate. The outcome is two dependent
      lineages within each population; inter-lineage matings produce workers, while
      intra-lineage matings produce reproductives. Both lineages are needed to produce
      a caste-functional colony, resulting in two reproductively isolated yet
      interdependent lineages. Pogonomyrmex populations composed of dependent lineages
      provide a unique opportunity to investigate genetic variation underlying
      phenotypic plasticity and its impact on the evolution of social structure.

PMID- 16995617
TI  - Genetic caste determination in harvester ants: possible origin and maintenance by
      cyto-nuclear epistasis.
AB  - While reproductive caste in eusocial insects is usually determined by
      environmental factors, in some populations of the harvester ants, Pogonomyrmex
      barbatus and P. rugosus, caste has been shown to have a strong genetic component.
      This system of genetic caste determination (GCD) is characterized by between
      caste nuclear variation and high levels of mitochondrial haplotype variation
      between alternative maternal lineages. Two previous genetic models, involving a
      single nuclear caste-determining locus or interactions between two nuclear loci,
      respectively, have been proposed to explain the GCD system. We propose a new
      model based on interactions between nuclear and mitochondrial genes that can
      better explain the co-maintenance of distinct nuclear and mitochondrial lineages.
      In our model, females with coevolved cyto-nuclear gene complexes, derived from
      intra-lineage mating, develop into gynes, while females with disrupted cyto
      nuclear complexes, derived from inter-lineage mating, develop into workers. Both
      haplodiploidy and inbreeding facilitate the buildup of such coevolved cyto
      nuclear complexes within lineages. In addition, the opportunity for both intra
      lineage and inter-lineage mating in polyandrous populations facilitates the
      accumulation of gyne-biasing genes. This model may also help to explain the
      evolution of workerless social, parasites. We discuss similarities of GCD and
      cytoplasmic male sterility in plants and how worker production of males would
      affect the stability of GCD. Finally, we propose experiments and observations
      that might help resolve the origin and maintenance of this unusual system of
      caste determination.

PMID- 16995618
TI  - Brood production and lineage discrimination in the red harvester ant
      (Pogonomyrmex barbatus).
AB  - In contrast to the system of caste determination in most social insects,
      reproductive caste determination in some populations of Pogonomyrmex barbatus has
      a genetic basis. Populations that exhibit genetic caste determination are
      segregated into two distinct, genetic lineages. Same-lineage matings result in
      female reproductives, while inter-lineage matings result in workers. To
      investigate whether founding P. barbatus queens lay eggs of reproductive
      genotype, and to determine the fate of those eggs, we genotyped eggs, larvae, and
      pupae produced by naturally inseminated, laboratory-raised queens. We show that
      founding dependent lineage queens do lay eggs of reproductive genotype, and that
      the proportion of reproductive genotypes decreases over the course of development
      from eggs to larvae to pupae. Because queens must mate with a male of each
      lineage to produce both workers and female reproductives, it would benefit queens
      to be able to distinguish males of the two lineages. Here we show that P.
      barbatus males from the two genetic lineages differ in their cuticular
      hydrocarbon profiles. Queens could use male cuticular hydrocarbons as cues to
      assess the lineage of males at the mating aggregation, and possibly keep mating
      until they have mated with males of both lineages.

PMID- 16995619
TI  - Behavioral regulation of genetic caste determination in a Pogonomyrmex population
      with dependent lineages.
AB  - The fate of a social insect colony is partially determined by its ability to
      allocate individuals to the caste most appropriate for the requirements for
      growth, maintenance, and reproduction. In pairs of dependent lineages of
      Pogonomyrmex barbatus, the allocation of individuals to the queen or worker caste
      is constrained by genotype, a system known as genetic caste determination (GCD).
      In mature GCD colonies, interlineage female eggs develop into sterile workers,
      while intralineage eggs become reproductively capable queens. Although the
      population-level consequences of this system have been intensively studied, the
      proximate mechanisms for GCD remain unknown. To elucidate these mechanisms, we
      brought newly mated queens into the laboratory and allowed them to establish
      colonies, nearly half of which unexpectedly produced virgin queens only seven
      months after colony founding. We genotyped eggs, workers, and the virgin queens
      from these colonies. Our results showed that queens in young colonies produce
      both interlineage and intralineage eggs, demonstrating that queens of GCD
      colonies indiscriminately use sperm of at least two lineages to fertilize their
      eggs. Intralineage eggs were more frequent in colonies producing virgin queens.
      These findings suggest that intralineage eggs are predetermined to become queens
      and that workers may cull these eggs when colonies are not producing queens.
      Virgin queens produced by young GCD colonies were smaller than field-caught
      virgin queens, and often had developmental problems. Hence, they are probably
      nonfunctional and represent an intense resource drain for developing colonies,
      not a contribution to colony fitness.

PMID- 16995620
TI  - Behavioral differences between Pogonomyrmex rugosus and dependent lineage (H1/H2)
      harvester ants.
AB  - The discovery of genetic caste determination (GCD) in populations of Pogonomyrmex
      harvester ants raises many questions about the evolution and persistence of such
      populations. The genetic caste determination arises from the existence of two
      distinct, but mutually dependent, genetic lineages within a population. Workers
      always develop from a combination of the two lineages, but their sister queens
      develop from within-lineage matings. Maintaining genetic caste determination
      appears to be costly because many queen-destined eggs are wasted when a colony is
      not in the reproductive stage, yet these populations appear to be widespread. We
      investigated whether inter-lineage workers have novel traits that give GCD
      colonies a selective advantage in certain environments. In particular, we
      compared ecologically relevant behavioral characteristics of inter-lineage
      workers in H-lineage colonies with co-occurring normal colonies of P. rugosus.
      First, we measured colony defensive response toward a simulated vertebrate
      predator. Second, we set up direct competitive foraging and recruitment
      experiments between dependent lineage and P. rugosus colonies. Last, we measured
      individual aggressive response to foreign inter-lineage and P. rugosus workers.
      We found that H1/H2 inter-lineage workers explored objects on the nest more
      thoroughly and responded much more aggressively to simulated predator disturbance
      than the P. rugosus colonies. In individual encounters, H1/H2 inter-lineage and
      P. rugosus workers were equally aggressive toward foreign ants, but both worker
      types could discriminate P. rugosus from inter-lineage intruders and were more
      aggressive toward ants of the alternate type to themselves. When competing
      directly for resources, however, P. rugosus colonies consistently dominated seed
      piles. In summary, H1/H2 GCD colonies show distinct behavioral differences, but
      there is no clear ecological advantage from the traits we examined.

PMID- 16995621
TI  - Extinction times in experimental populations.
AB  - Predicting population extinctions is a key element of quantitative conservation
      biology and population ecology. Although stochastic population theories have long
      been used to obtain theoretical distributions of population extinction times,
      model-based predictions have rarely been tested. Here I report results from a
      quantitative analysis of extinction time in 281 experimental populations of water
      fleas (Daphnia magna) in variable environments. To my knowledge, this is the
      first quantitative estimate of the shape of the distribution of population
      extinction times based on extinction data for any species. The finding that the
      distribution of population extinction times was extraordinarily peaked is
      consistent with theoretical predictions for density-independent populations, but
      inconsistent with predictions for density-dependent populations. The tail of the
      extinction time distribution was not exponential. These results imply that our
      current theories of extinction are inadequate. Future work should focus on how
      demographic stochasticity scales with population size and effects of nonrandom
      variable environments on population growth and decline.

PMID- 16995622
TI  - Species abundance distributions result from body size-energetics relationships.
AB  - Abundance distributions are a central characteristic of ecosystems. Certain
      distributions have been derived from theoretical models of community
      organization, and therefore the fit of data to these distributions has been
      proposed as a test of these theories. However, it is shown here that the
      geometric sequence distribution can be derived directly from the empirical
      relationship between population density and body size, with the assumption of
      random or uniform body size distributions on a log scale (as holds at local
      scales). The geometric sequence model provides a good to excellent fit to
      empirical data. The presence of noise in the relationship between population
      density and body size creates a curve that begins to approximate a lognormal
      species abundance distribution as the noise term increases. For continental-scale
      data in which the body size distribution is not flat, the result of sampling
      tends again toward the lognormal. Repeat sampling over time smooths out species
      population fluctuations and damps out the noise, giving a more precise geometric
      sequence abundance distribution. It is argued that the direct derivation of this
      distribution from empirical relationships gives it priority over distributions
      derived from complex theoretical community models.

PMID- 16995623
TI  - Adding infection to injury: synergistic effects of predation and parasitism on
      amphibian malformations.
AB  - We explored the importance of interactions between parasite infection and
      predation in driving an emerging phenomenon of conservation importance: amphibian
      limb malformations. We suggest that injury resulting from intraspecific predation
      in combination with trematode infection contributes to the frequency and severity
      of malformations in salamanders. By integrating field surveys and experiments, we
      evaluated the individual and combined effects of conspecific attack and parasite
      (Ribeiroia ondatrae) infection on limb development of long-toed salamanders
      (Ambystoma macrodactylum). In the absence of Ribeiroia, abnormalities involved
      missing digits, feet, or limbs and were similar to those produced by
      cannibalistic attack in experimental trials. At field sites that supported
      Ribeiroia, malformations were dominated by extra limbs and digits.
      Correspondingly, laboratory exposure of larval salamanders to Ribeiroia cercariae
      over a 30-day period induced high frequencies of malformations, including extra
      digits, extra limbs, cutaneous fusion, and micromelia. However, salamander limbs
      exposed to both injury and infection exhibited 3-5 times more abnormalities than
      those exposed to either factor alone. Infection also caused significant delays in
      limb regeneration and time-to-metamorphosis. Taken together, these results help
      to explain malformation patterns observed in natural salamander populations while
      emphasizing the importance of interactions between parasitism and predation in
      driving disease.

PMID- 16995624
TI  - Spatial scale of the patchiness of plant poisons: a critical influence on
      foraging efficiency.
AB  - Generalist mammalian browsers and folivores feed on a range of chemically
      different plant species, which may assist them in diluting toxins and
      diversifying nutrient consumption. The frequency and order in which their diets
      are mixed are important determinants of intake. As a result, the degree of plant
      heterogeneity in an environment, and the spatial scale at which this occurs,
      should directly influence herbivore foraging decisions. We tested whether
      altering the Spatial scale of plants, and thus plant secondary metabolites
      (PSMs), affected foraging efficiency of a generalist folivore, the common
      brushtail possum (Trichosurus vulpecula). First, we demonstrated that possums
      were able to consume more from a mixed diet of two chemically different species,
      Eucalyptus globulus and E. tenuiramis, than when either of these species was
      offered alone. We then tested whether altering the spatial scale between E.
      globulus and E. tenuiramis, as small- or large-scale plant heterogeneity
      "patches," affected possum foraging behavior and, ultimately, their foraging
      efficiency. Possums increased their foraging efficiency when the spatial scale of
      plant heterogeneity was small rather than large. We argue that the ability to
      regularly switch diets, when plant spatial distribution is at a small scale,
      reduces the negative effects of PSM ingestion. We predict that the heterogeneity
      of plant patches, in relation to PSM distribution, and the scale at which this
      occurs across a landscape, are critical factors that influence foraging
      efficiency and, ultimately, fitness of mammalian herbivores. This research
      provides a fundamental link between plant chemistry, foraging, and habitat
      heterogeneity.

PMID- 16995625
TI  - Movement of foraging Tundra Swans explained by spatial pattern in cryptic food
      densities.
AB  - We tested whether Tundra Swans use information on the spatial distribution of
      cryptic food items (below ground Sago pondweed tubers) to shape their movement
      paths. In a continuous environment, swans create their own food patches by
      digging craters, which they exploit in several feeding bouts. Series of short (<1
      m) intra-patch movements alternate with longer inter-patch movements (>1 m).
      Tuber biomass densities showed a positive spatial auto-correlation at a short
      distance (<3 m), but not at a larger distance (3-8 m). Based on the spatial
      pattern of the food distribution (which is assumed to be pre-harvest information
      for the swan) and the energy costs and benefits for different food densities at
      various distances, we calculated the optimal length of an inter-patch movement. A
      swan that moves to the patch with the highest gain rate was predicted to move to
      the adjacent patch (at 1 m) if the food density in the current patch had been
      high (>25 g/m2) and to a more distant patch (at 7-8 m) if the food density in the
      current patch had been low (<25 g/m2). This prediction was tested by measuring
      the response of swans to manipulated tuber densities. In accordance with our
      predictions, swans moved a long distance (>3 m) from a low-density patch and a
      short distance (<3 m) from a high-density patch. The quantitative agreement
      between prediction and observation was greater for swans feeding in pairs than
      for solitary swans. The result of this movement strategy is that swans visit high
      density patches at a higher frequency than on offer and, consequently, achieve a
      38% higher long-term gain rate. Swans also take advantage of spatial variance in
      food abundance by regulating the time in patches, staying longer and consuming
      more food from rich than from poor patches. We can conclude that the shape of the
      foraging path is a reflection of the spatial pattern in the distribution of tuber
      densities and can be understood from an optimal foraging perspective.

PMID- 16995626
TI  - Tissue type matters: selective herbivory on different life history stages of an
      isomorphic alga.
AB  - Selective grazing by herbivores can have large effects on the population dynamics
      and community structure of primary producers. However, the ecological impacts of
      within-species herbivore preference for tissues of different phases (e.g., ploidy
      levels) or reproductive status remain relatively poorly known, especially among
      algae and other species with free-living haploid (gametophyte) and diploid
      (sporophyte) phases. We tested for herbivore selectivity among tissue types of
      the isomorphic (identical haploid and diploid free-living stages) red alga
      Mazzaella flaccida. Laboratory feeding assays demonstrated that the snail Tegula
      funebralis exhibited more than a threefold preference for gametophyte
      reproductive tissue over other tissue types, due to morphological differences. In
      contrast, the urchin Strongylocentrotus purpuratus did not distinguish as clearly
      between gametophytes and sporophytes; but it did prefer sporophyte reproductive
      to nonreproductive tissue, due to differences in water-soluble chemicals. Field
      surveys of grazer damage on M. flaccida blades were consistent with these
      laboratory preferences, with more damage found on gametophytes than sporophytes
      and reproductive than nonreproductive tissues. Differential fecundity can
      contribute to a skew in relative frequencies of phases in the field, and our
      results suggest that differential grazing by snails may contribute to this
      pattern and thus play a role in algal population biology.

PMID- 16995627
TI  - Shifts in grassland invasibility: effects of soil resources, disturbance,
      composition, and invader size.
AB  - There is an emerging recognition that invasibility is not an intrinsic community
      trait, but is a condition that fluctuates from interactions between environmental
      forces and residential characters. Elucidating the spatiotemporal complexities of
      invasion requires inclusion of multiple, ecologically variable factors within
      communities of differing structure. Water and nutrient amendments, disturbance,
      and local composition affect grassland invasibility but no study has
      simultaneously integrated these, despite evidence that they frequently interact.
      Using a split-plot factorial design, we tested the effects of these factors on
      the invasibility of C3 pasture communities by smooth pigweed Amaranthus hybridus
      L., a problematic C4 forb. We sowed seeds and transplanted 3-week old seedlings
      of A. hybridus into plots containing monocultures and mixtures of varying
      composition, subjected plots to water, soil disturbance, and synthetic bovine
      urine (SBU) treatments, and measured A. hybridus emergence, recruitment, and
      growth rate. Following SBU addition, transplanted seedling growth increased in
      all plots but differed among legume and nonlegume monocultures and mixtures of
      these plant types. However, SBU decreased the number and recruitment rate of
      emerged seedlings because high residential growth reduced light availability.
      Nutrient pulses can therefore have strong but opposing effects on invasibility,
      depending on when they coincide with particular life history stages of an
      invader. Indeed, in SBU-treated plots, small differences in height of
      transplanted seedlings early on produced large differences in their final
      biomass. All facilitative effects of small-scale disturbance on invasion success
      diminished when productivity-promoting factors were present, suggesting that
      disturbance patch size is important. Precipitation-induced invasion resistance of
      C3 pastures by a C4 invader was partly supported. In grazed grasslands, these
      biotic and environmental factors vary across scales and interact in complex ways
      to affect invasibility, thus a dynamic patch mosaic of differential invasion
      resistance likely occurs in single fields. We propose that disturbance patch
      size, grazing intensity, soil resource availability, and resident composition are
      inextricably linked to grassland invasions and comment on the utility of
      community attributes as reliable predictors of invasibility. Lastly, we suggest
      temporal as well as spatial coincidences of multiple invasion facilitators
      dictate the window of opportunity for invasion.

PMID- 16995628
TI  - CO2-enrichment and nutrient availability alter ectomycorrhizal fungal
      communities.
AB  - Ectomycorrhizal fungi (EMF), a phylogenetically and physiologically diverse
      guild, form symbiotic associations with many trees and greatly enhance their
      uptake of nutrients and water. Elevated CO2, which increases plant carbon supply
      and demand for mineral nutrients, may change the composition of the EMF
      community, possibly altering nutrient uptake and ultimately forest productivity.
      To assess CO2 effects on EMF communities, we sampled mycorrhizae from the FACTS-I
      (Forest-Atmosphere Carbon Transfer and Storage) research site in Duke Forest,
      Orange County, North Carolina, USA, where Pinus taeda forest plots are maintained
      at either ambient or elevated CO2 (200 ppm above ambient) concentrations.
      Mycorrhizae were identified by DNA sequence similarity of the internal
      transcribed spacer ribosomal RNA gene region. EMF richness was very high; 72
      distinct phylotypes were detected from 411 mycorrhizal samples. Overall EMF
      richness and diversity were not affected by elevated CO2, but increased CO2
      concentrations altered the relative abundances of particular EMF taxa colonizing
      fine roots, increased prevalence of unique EMF species, and led to greater EMF
      community dissimilarity among individual study plots. Natural variation among
      plots in mean potential net nitrogen (N) mineralization rates was a key
      determinant of EMF community structure; increasing net N mineralization rate was
      negatively correlated with EMF richness and had differential effects on the
      abundance of particular EMF taxa. Our results predict that, at CO2 concentrations
      comparable to that predicted for the year 2050, EMF community composition and
      structure will change, but diversity will be maintained. In contrast, high soil N
      concentrations can negatively affect EMF diversity; this underscores the
      importance of considering CO2 effects on forest ecosystems in the context of
      background soil chemical parameters and other environmental perturbations such as
      acid deposition or fertilizer runoff.

PMID- 16995629
TI  - Tree species effects on decomposition and forest floor dynamics in a common
      garden.
AB  - We studied the effects of tree species on leaf litter decomposition and forest
      floor dynamics in a common garden experiment of 14 tree species (Abies alba, Acer
      platanoides, Acer pseudoplatanus, Betula pendula, Carpinus betulus, Fagus
      sylvatica, Larix decidua, Picea abies, Pinus nigra, Pinus sylvestris, Pseudotsuga
      menziesii, Quercus robur, Quercus rubra, and Tilia cordata) in southwestern
      Poland. We used three simultaneous litter bag experiments to tease apart species
      effects on decomposition via leaf litter chemistry vs. effects on the
      decomposition environment. Decomposition rates of litter in its plot of origin
      were negatively correlated with litter lignin and positively correlated with mean
      annual soil temperature (MAT(soil)) across species. Likewise, decomposition of a
      common litter type across all plots was positively associated with MAT(soil), and
      decomposition of litter from all plots in a common plot was negatively related to
      litter lignin but positively related to litter Ca. Taken together, these results
      indicate that tree species influenced microbial decomposition primarily via
      differences in litter lignin (and secondarily, via differences in litter Ca),
      with high-lignin (and low-Ca) species decomposing most slowly, and by affecting
      MAT(soil), with warmer plots exhibiting more rapid decomposition. In addition to
      litter bag experiments, we examined forest floor dynamics in each plot by mass
      balance, since earthworms were a known component of these forest stands and their
      access to litter in litter bags was limited. Forest floor removal rates estimated
      from mass balance were positively related to leaf litter Ca (and unrelated to
      decay rates obtained using litter bags). Litter Ca, in turn, was positively
      related to the abundance of earthworms, particularly Lumbricus terrestris. Thus,
      while species influence microbially mediated decomposition primarily through
      differences in litter lignin, differences among species in litter Ca are most
      important in determining species effects on forest floor leaf litter dynamics
      among these 14 tree species, apparently because of the influence of litter Ca on
      earthworm activity. The overall influence of these tree species on leaf litter
      decomposition via effects on both microbial and faunal processing will only
      become clear when we can quantify the decay dynamics of litter that is
      translocated belowground by earthworms.

PMID- 16995630
TI  - Contrasting structure and composition of the understory in species-rich tropical
      rain forests.
AB  - In large samples of trees > or = 1 cm dbh (more than 1 million trees and 3000
      species), in six lowland tropical forests on three continents, we assigned
      species with >30 individuals to one of six classes of stature at maturity (SAM).
      We then compared the proportional representation of understory trees (1-2 cm dbh)
      among these classes. The understory of the three Asian sites was predominantly
      composed of the saplings of large-canopy trees whereas the African and American
      sites were more richly stocked with trees of the smaller SAM classes. Differences
      in class representation were related to taxonomic families that were present
      exclusively in one continent or another. Families found in the Asian plots but
      not in the American plot (e.g., Dipterocarpaceae, Fagaceae) were predominantly
      species of the largest SAM classes, whereas families exclusive to the American
      plots (e.g., Melastomataceae sensu stricto, Piperaceae, and Malvaceae
      [Bombacacoidea]) were predominantly species of small classes. The African plot
      was similar to Asia in the absence of those American families rich in understory
      species, while similar to America in lacking the Asian families rich in canopy
      species. The numerous understory species of Africa were chiefly derived from
      families shared with Asia and/or America. The ratio of saplings (1-2 cm dbh) to
      conspecific canopy trees (>40 cm dbh) was lower in American plots than in the
      Asian plots. Possible explanations for these differences include phenology,
      moisture and soil fertility regimes, phyletic constraints, and the role of early
      successional plants in forest development. These results demonstrate that
      tropical forests that appear similar in tree number, basal area, and the family
      taxonomy of canopy trees nonetheless differ in ecological structure in ways that
      may impact the ecology of pollinators, dispersers, and herbivores and might
      reflect fundamental differences in canopy tree regeneration.

PMID- 16995631
TI  - Modeling leaf dispersal in mixed hardwood forests using a ballistic approach.
AB  - In mixed-species stands, modeling leaf litter dispersal is important to predict
      the physical and chemical characteristics of the forest floor, which plays a
      major role in nutrient cycling and in plant population dynamics. In this study, a
      spatially explicit model of leaf litterfall was developed and compared with two
      other models. These three models were calibrated for a mixed forest of oak and
      beech using litterfall data from mapped forest plots. All models assumed that an
      allometric equation described individual leaf litter production, but they
      strongly differed in the modeling of the probability density of leaf shedding
      with distance from source trees. Two models used a negative exponential function
      to account for leaf dispersal with distance, and this function was allowed to
      vary according to wind direction in one of them. In contrast, our approach was
      based on a simple ballistic equation considering release height, wind speed, wind
      direction, and leaf fall velocity; the distributions of wind speeds and wind
      directions were modeled according to a Weibull and a Von Mises distribution,
      respectively. Using an independent validation data set, all three models provided
      predictions well correlated to measurements (r > 0.83); however, the two models
      with a direction-dependent component were slightly more accurate. In addition,
      parameter estimates of the ballistic model were in close agreement with a foliar
      litter production equation derived from the literature for beech and with wind
      characteristics measured during leaf litterfall for both species. Because of its
      mechanistic background, such a spatially explicit model might be incorporated as
      a litterfall module in larger models (nutrient cycling, plant population
      dynamics) or used to determine the manner in which patch size in mixed-species
      stands influences litter mixture.

PMID- 16995632
TI  - Forest dynamics after successive spruce budworm outbreaks in mixedwood forests.
AB  - In order to assess the long-term spatiotemporal influence of the spruce budworm
      in sub-boreal mixedwood forests, we studied the effect of three successive
      outbreaks in a region of western Quebec, Canada. We used dendrochronology to
      detect past outbreaks in three areas (111-185 ha), based on the recruitment age
      of balsam fir (Abies balsamea) and on growth patterns of white spruce (Picea
      glauca), the two main host species of this defoliating insect. We also used a
      series of aerial photographs taken between 1935 and 2003 to evaluate overstory
      mortality and post-outbreak succession patterns in these same areas. Individual
      outbreaks had a spatially homogenous impact on host species throughout the
      region, but successive outbreaks differed in intensity: the two outbreaks around
      1910 and 1980 caused widespread mortality in the overstory, but an outbreak
      around 1945 had little impact, probably because the forest mosaic had not yet
      recuperated from the 1910 outbreak. No clear outbreak was detected in the later
      part of the 19th century. In portions of the study areas where the 1910 outbreak
      had a major impact, between 36% and 50% of the stands were reoccupied by balsam
      fir stands in the period up to the 1980 outbreak (cyclic succession), the rest
      being at least partly replaced by nonhost species such as Betula spp. Changes in
      forest composition after the 1910 outbreak were mostly associated with upper
      slope positions in all study areas. The 1980 outbreak also had a higher impact
      than earlier outbreaks in lower-slope positions dominated by black spruce (Picea
      mariana)-balsam fir mixtures. These results suggest that, at the regional scale,
      the abundance of mature or over-mature balsam fir stands does not determine the
      outbreak cycle. When an outbreak occurs, however, its impact will be strongly
      constrained by forest characteristics such as stand composition and structure,
      which are themselves influenced by previous disturbances and slope position.

PMID- 16995633
TI  - Range-restricted, specialist Bornean butterflies are less likely to recover from
      ENSO-induced disturbance.
AB  - The forest fires induced by the El Nino Southern Oscillation (ENSO) in 1997-1998
      resulted in the temporary extirpation of more than 100 lowland butterfly species
      at a forest site in Borneo. Species with more restricted ranges were less likely
      to recover over the following four years. Matched-pair analyses revealed that
      species with lower initial abundances, restricted geographic ranges, and more
      specialized larvae were less likely to return. Specialization differed
      predictably between the (more generalist) wide-range and (more specialized)
      restricted-range species in our data set, and both geographic range and level of
      specialization were important in multivariate models. These are the first
      observations directly linking extent of occurrence, ecological specialization,
      and observed recovery following local extirpation. If recovery time exceeds the
      frequency of disturbance, local extirpation can lead to local extinction. Given
      that ENSO-induced disturbances are increasing in frequency, in severity, and in
      geographic scale, these results suggest that specialist species with restricted
      geographic ranges could be at particularly high risk of global extinction.

PMID- 16995634
TI  - Transient population dynamics in periodic matrix models: methodology and effects
      of cyclic permutations.
AB  - Many biological populations are subject to periodically changing environments
      such as years with or without fire, or rotation of crop types. The dynamics and
      management options for such populations are frequently investigated using
      periodic matrix models. However the analysis is usually limited to long-term
      results (asymptotic population growth rate and its sensitivity to perturbations
      of vital rates). In non-periodic matrix models it has been shown that long-term
      results may be misleading as populations are rarely in their stable structure. We
      therefore develop methods to analyze transient dynamics of periodic matrix
      models. In particular, we show how to calculate the effects of perturbations on
      population size within and at the end of environmental cycles. Using a model of a
      weed population subject to a crop rotation, we show that different cyclic
      permutations produce different patterns of sensitivity of population size and
      different population sizes. By examining how the starting environment interacts
      with the initial conditions, we explain how different patterns arise. Such
      understanding is critical to developing effective management and monitoring
      strategies for populations subject to periodically recurring environments.

PMID- 16995635
TI  - Eigenanalysis of selection ratios from animal radio-tracking data.
AB  - The development of methods to analyze habitat selection when resources are
      defined by several categories (e.g., vegetation types) is a topical issue in
      radio-tracking studies. The White and Garrott statistic, an extension of the
      widely used test of Neu et al., can be used to determine whether habitat
      selection is significant. As well, Manly's selection ratio, a particularly useful
      measure of resource selectivity by resource users, allows detection of the most
      strongly selected habitat types. However, when both the number of animals and
      types of habitat are large, the biologist often has to deal with an excessively
      large number of measures. In this paper we present a new method, the
      eigenanalysis of selection ratios, that generalizes these two common methods
      within the framework of eigenanalyses. This method undertakes an additive linear
      partitioning of the White and Garrott statistic, so that the difference between
      habitat use and availability is maximized on the first factorial axes. The
      eigenanalysis of selection ratios is therefore optimal in habitat selection
      studies. Although we primarily consider the case where the habitat availability
      is the same for all animals (design II), we also extend this analysis to the case
      where the habitat availability varies from one animal to another (design III). An
      application of this method is provided using radio-tracking data collected on 17
      squirrels in five habitat types. The results indicate variability in habitat
      selection, with two groups of animals displaying two patterns of preference. This
      difference between the two groups is explained by the patch structure of the
      study area. Because this method is mainly exploratory, and therefore does not
      rely on any distributional assumption, we recommend its use in studies of habitat
      selection.

PMID- 16995636
TI  - The fitting of general force-of-infection models to wildlife disease prevalence
      data.
AB  - Researchers and wildlife managers increasingly find themselves in situations
      where they must deal with infectious wildlife diseases such as chronic wasting
      disease, brucellosis, tuberculosis, and West Nile virus. Managers are often
      charged with designing and implementing control strategies, and researchers often
      seek to determine factors that influence and control the disease process. All of
      these activities require the ability to measure some indication of a disease's
      foothold in a population and evaluate factors affecting that foothold. The most
      common type of data available to managers and researchers is apparent prevalence
      data. Apparent disease prevalence, the proportion of animals in a sample that are
      positive for the disease, might seem like a natural measure of disease's
      foothold, but several properties, in particular, its dependency on age structure
      and the biasing effects of disease-associated mortality, make it less than ideal.
      In quantitative epidemiology, the "force of infection," or infection hazard, is
      generally the preferred parameter for measuring a disease's foothold, and it can
      be viewed as the most appropriate way to "adjust" apparent prevalence for age
      structure. The typical ecology curriculum includes little exposure to
      quantitative epidemiological concepts such as cumulative incidence, apparent
      prevalence, and the force of infection. The goal of this paper is to present
      these basic epidemiological concepts and resulting models in an ecological
      context and to illustrate how they can be applied to understand and address basic
      epidemiological questions. We demonstrate a practical approach to solving the
      heretofore intractable problem of fitting general force-of-infection models to
      wildlife prevalence data using a generalized regression approach. We apply the
      procedures to Mycobacterium bovis (bovine tuberculosis) prevalence in bison
      (Bison bison) in Wood Buffalo National Park, Canada, and demonstrate strong age
      dependency in the force of infection as well as an increased mortality hazard in
      positive animals.

PMID- 16995637
TI  - Prey growth and size-dependent predation in juvenile estuarine fishes:
      experimental and model analyses.
AB  - The outcome of predation interactions between growing, size-structured predator
      and prey cohorts is difficult to predict. We manipulated the food resources
      available to juvenile spot subject to predation from southern flounder in a 60
      day replicated pond experiment to test the hypothesis that spot growing slowly
      would experience higher predation mortality and stronger selection against small
      individuals than those growing rapidly. A nearly threefold difference in average
      growth rate between fast- and slow-growth treatments led to twofold higher
      predation mortality of slow-growing spot. Relative to no-flounder controls,
      larger spot were overrepresented at the end of the experiment in both treatments,
      but the magnitude of flounder size selection was much greater in the slow-growth
      treatment. The experimental results agreed qualitatively, but not quantitatively,
      with predictions from a prior size-dependent foraging model. In particular, the
      model significantly underestimated observed shifts in spot size structure to
      larger sizes. We hypothesized that competitive release and associated increases
      in spot growth due to thinning by flounder might reconcile this difference, and
      extended the model to incorporate this process. We then used the model to
      estimate the relative contribution of these two confounded predator effects (size
      selective predation and thinning) to observed shifts in spot size structure.
      Model simulations indicated that the combined effects of size-selective predation
      and thinning could account for nearly all of the observed shift in spot size
      structure, but that thinning was the more important process. Our results
      highlight the utility of combining experimental and modeling approaches to
      unravel the complexities underlying interactions between growing, size-structured
      predator and prey cohorts.

PMID- 16995638
TI  - Disturbance influences oyster community richness and evenness, but not diversity.
AB  - Foundation species in space-limited systems can increase diversity by creating
      habitat, but they may also reduce diversity by excluding primary space
      competitors. These contrasting forces of increasing associate diversity and
      suppressing competitor diversity have rarely been examined experimentally with
      respect to disturbance. In a benthic marine community in central California,
      where native oysters are a foundation species, we tested how disturbance
      influenced overall species richness, evenness, and diversity. Surprisingly,
      overall diversity did not peak across a disturbance gradient because, as
      disturbance decreased, decreases in overall species evenness opposed increases in
      overall species richness. Decreasing disturbance intensity (high oyster
      abundance) led to increasing species richness of sessile and mobile species
      combined. This increase was due to the facilitation of secondary sessile and
      mobile species in the presence of oysters. In contrast, decreasing disturbance
      intensity and high oyster abundance decreased the evenness of sessile and mobile
      species. Three factors likely contributed to this decreased evenness: oysters
      reduced abundances of primary sessile species due to space competition; oysters
      supported more rare mobile species; and oysters disproportionately increased the
      relative abundance of a few common mobile species. Our results highlight the need
      for further studies on how disturbance can differentially affect the evenness and
      richness of different functional groups, and ultimately how these differences
      affect the relationship between overall diversity and ecosystem function.

PMID- 16995639
TI  - Linking marine resources to ecotonal shifts of water uptake by terrestrial dune
      vegetation.
AB  - As evidence mounts that sea levels are rising, it becomes increasingly important
      to understand the role of ocean water within terrestrial ecosystem dynamics.
      Coastal sand dunes are ecosystems that occur on the interface of land and sea.
      They are classic ecotones characterized by zonal distribution of vegetation in
      response to strong gradients of environmental factors from the ocean to the
      inland. Despite the proximity of the dune ecosystem to the ocean, it is generally
      assumed that all vegetation utilizes only freshwater and that water sources do
      not change across the ecotone. Evidence of ocean water uptake by vegetation would
      redefine the traditional interpretation of plant-water relations in the dune
      ecosystem and offer new ideas for assessing maritime influences on function and
      spatial distribution of plants across the dune. The purpose of this study was to
      identify sources of water (ocean, ground, and rain) taken up by vegetation using
      isotopic analysis of stem water and to evaluate water uptake patterns at the
      community level based on the distribution and assemblage of species. Three
      coastal dune systems located in southern Florida, USA, and the Bahamian
      bank/platform system were investigated. Plant distributions across the dune were
      zonal for 61-94% of the 18 most abundant species at each site. Species with their
      highest frequency on the fore dune (nearest the ocean) indicate ocean water
      uptake as evidenced by delta 18O values of stem water. In contrast, species most
      frequent in the back dune show no evidence of ocean water uptake. Analysis of
      species not grouped by frequency, but instead sampled along a transect from the
      ocean toward the inland, indicates that individuals from the vegetation
      assemblage closest to the ocean had a mixed water-harvesting strategy
      characterized by plants that may utilize ocean, ground-, and/or rainwater. In
      contrast, the inland vegetation relies mostly on rainwater. Our results show
      evidence supporting ocean water use by dune vegetation and demonstrate an
      exciting relationship between seawater and ecotonal shifts in plant function of a
      terrestrial ecosystem.

PMID- 16995640
TI  - Seaweed diversity enhances nitrogen uptake via complementary use of nitrate and
      ammonium.
AB  - The consequences of declining biodiversity remain controversial, in part because
      many studies focus on a single metric of ecosystem functioning and fail to
      consider diversity's integrated effects on multiple ecosystem functions. We used
      tide pool microcosms as a model system to show that different conclusions about
      the potential effects of producer diversity on ecosystem functioning may result
      when ecosystem functions are measured separately vs. together. Specifically, we
      found that in diverse seaweed assemblages, uptake of either nitrate or ammonium
      alone was equal to the average of the component monocultures. However, when
      nitrate and ammonium were available simultaneously, uptake by diverse assemblages
      was 22% greater than the monoculture average because different species were
      complementary in their use of different nitrogen forms. Our results suggest that
      when individual species have dominant effects on particular ecosystem processes
      (i.e., the sampling effect), multivariate complementarity can arise if different
      species dominate different processes. Further, these results suggest that similar
      mechanisms (complementary nutrient uptake) may underlie diversity-functioning
      relationships in both algal and vascular-plant-based systems.

PMID- 16995641
TI  - Biomedical journals: keeping up and reading critically.
AB  - By extrapolation from studies of physicians, knowledge and practice of laboratory
      animal medicine and science are expected to become progressively more outdated
      the longer practitioners are out of school. Keeping up with current literature
      and practice is a challenge that necessitates the use of many different sources
      of continuing education. Both veterinarians and physicians consistently list
      journals as the most beneficial source of new information. Accordingly, they must
      select from the veterinary and biomedical literature articles that report
      original studies and systematic reviews and recognize and respond to valid new
      knowledge to improve diagnostic and therapeutic approaches and maintain
      consistent clinical skills. Other objectives include selecting journals for
      general information and for information relevant or specific to one's field of
      research. Lastly, candidates for board certification need to read articles from
      journals that potentially provide the basis for questions on the examination.
      'High-impact' journals should be identified, and articles should be reviewed
      critically. In a survey of recent candidates for laboratory animal medicine board
      examination, these journals included Contemporary Topics (now JAALAS),
      Comparative Medicine, ILAR Journal, and Laboratory Animals. Strategies for coping
      with the challenge of staying current with the literature include wise use of
      technology, journal clubs, and consultation with colleagues. A laboratory animal
      practitioner can become a better scientist and clinician by evaluating the
      research performed by others. Thorough, critical review of biomedical literature
      is paramount to these goals.

PMID- 16995642
TI  - Job dynamics of veterinary professionals in an academic research institution. I.
      Retention and turnover of veterinary technicians.
AB  - The turnover of veterinary technicians within an animal resources program
      averaged 33% annually over 18 y, peaking at 67% in 1998 to 1999. Insufficient
      retention of veterinary technicians led to diversion of veterinarian effort to
      technical tasks and to increased allocation of administrative resources for
      supervising and managing an expanding team of veterinary technicians. To identify
      factors and trends related to poor retention, address any causes, and reduce
      turnover, a retrospective analysis of employment records was done. The retention
      of veterinary technicians was significantly greater for the 9 technicians hired
      from veterinary private practice rather than for any of 3 other general sources:
      promotions from the animal care staff, transfers from other research
      institutions, and miscellaneous sources. Veterinary technician turnover was
      reduced from a mean of 60% over 1995 to 1999 to an average of 26% during 2000 to
      2004. Higher retention was associated with management practices that included
      renewed concentration on recruiting and interviewing strategies and emphasis on
      training and career development including merit raises for technician
      certification through the American Association for Laboratory Animal Science.
      Higher retention yielded correspondingly greater experience on the job as the
      mean tenure increased from 1.1 y in 2000 to 2.8 y in 2004. The most valued
      attributes related to employment by veterinary technicians as determined by
      survey were to do meaningful work, earn a good living, and have a committed team
      of coworkers.

PMID- 16995643
TI  - Job dynamics of veterinary professionals in an academic research institution. II.
      Veterinary technician attendance, absenteeism, and pay distribution.
AB  - To understand and better manage attendance and overtime for a team of veterinary
      technicians, a retrospective analysis of the attendance and time card records was
      done over a 2-y period. The findings show that veterinary technicians were in the
      workplace for a combination of straight time and overtime hours for approximately
      89% of all compensated hours. The remainder of paid compensation was for vacation
      (4%), holidays (4%), and sick leave (3%). This team of veterinary technicians
      earned significantly more overtime hours, as much as 9% of total annual
      compensated hours, than the reported 3% standard for animal resources programs
      nationwide. The majority of overtime hours (61%) were for assigned weekend and
      holiday duty and after-hours veterinary medical emergencies. Veterinary
      technicians expended sick leave at 75% of the amount accrued and at a
      statistically significantly rate 65% higher than the national average for
      unscheduled absences for hourly personnel in animal resources programs. Because
      the direct cost of absenteeism may exceed 645 dollars per employee annually and
      because work inappropriately done at premium pay outside of business hours is a
      controllable expense, sound management of attendance and overtime is important in
      cost containment for animal resources programs.

PMID- 16995644
TI  - Use of enclosures with functional vertical space by captive rhesus monkeys
      (Macaca mulatta) involved in biomedical research.
AB  - We assessed space use by 2 pairs of captive female rhesus monkeys recently
      transferred into 2 enclosures moderately larger than their former traditional
      research cages and providing elevated perches at or above human eye level for all
      monkeys. This new space did not affect the ongoing biomedical research in which
      these captive monkeys were involved, and we sought to determine whether they used
      the elevated positions preferentially, as do wild animals. The frequency and
      duration of visits at each of the 9 distinct regions within these enclosures was
      calculated during 30-min morning and evening sessions over 20 d. We found that
      the monkeys frequented all regions of their enclosures in a similar manner during
      both morning and evening sessions. However, the duration spent at each region
      varied significantly between morning and evening sessions, with high perches
      being chosen preferentially in the evenings. Overall, the monkeys spent the
      majority of their time at elevated positions. These results support the view that
      access to functional vertical space provides a preferred environment for species-
      specific behavior and is an option that should be considered by other research
      facilities.

PMID- 16995645
TI  - Effects of outdoor housing on self-injurious and stereotypic behavior in adult
      male rhesus macaques (Macaca mulatta).
AB  - We examined the effects of outdoor housing on self-injurious and stereotypic
      behavior in adult male rhesus macaques with a history of self-wounding that were
      previously singly housed indoors for at least 4 y prior to the study. Baseline
      behavioral observations were collected over 2.5 mo. In phase 1, animals were
      relocated outdoors in 1 of 2 experimental conditions, group-housed (n = 8) or
      single-housed (n = 5), for 6 wk. In phase 2, group-housed animals were observed
      outdoors for an additional 6 wk. Behavioral observations were done using focal
      sampling techniques. In phase 1, rates of self-biting and self-directed
      stereotypies and time spent displaying idiosyncratic self-directed stereotypies
      decreased significantly when group- and single-housed animals were housed
      outdoors. Rates of yawning and scratching were significantly decreased for group-
      and single-housed animals and, for group-housed animals, self-grooming decreased
      with outdoor housing. In phase 2, rates of self-biting, time engaging in
      idiosyncratic self-directed stereotypies, and yawning remained significantly
      lower during weeks 7 through 12 (outdoor housing) compared with those under
      indoor housing. Rates of scratching and time spent self-grooming decreased
      significantly during the first 6 wk but then returned to baseline levels. Our
      findings suggest that self-biting and self-directed stereotypic behavior in
      rhesus macaques with a history of self-injurious behavior is significantly
      reduced by outdoor housing regardless of whether animals are socially or
      individually housed.

PMID- 16995646
TI  - Individual and group housing in N-type Ca2+ channel alpha1B subunit-deficient
      mice differently affect motor activity.
AB  - N-type Ca2+ channel alpha1B-deficient mice have increased activity (ambulation,
      repetitive behavior, and rearing combined), suggesting contribution by the N-type
      Ca2+ channel, localized in the plasma membrane and essential for neurotransmitter
      release, on motor activity. We evaluated the effect of a 6-wk postweaning period
      of either individual or group housing on the activity displayed in a novel
      environment with or without previous habituation. Without habituation, male
      homozygous alpha1B-deficient mice showed significantly higher activity than wild
      type controls, with no influence of the housing condition. When habituated,
      hyperactivity was seen in individually housed but not group-housed homozygous
      alpha1B-deficient mice. The results indicate that controlling for housing
      condition can be important when phenotypically analyzing mutant mice.

PMID- 16995647
TI  - Acetaminophen self-administered in the drinking water increases the pain
      threshold of rats (Rattus norvegicus).
AB  - Previous studies have suggested that the addition of flavored acetaminophen
      suspension (for example, Children's Tylenol) in the drinking water of rats may
      not be effective in producing postoperative analgesia because of low levels of
      consumption. However, these investigations neither measured analgesia nor
      compared the consumption by rats that had undergone surgery with that by
      unmanipulated rats. The present study reports that although unmanipulated rats
      naive to the taste of flavored acetaminophen do indeed drink significantly less
      of this liquid than tap water, they drank sufficient amounts of the acetaminophen
      containing solution to significantly raise pain thresholds, as measured by the
      hot-plate test. Moreover, rats that had undergone surgery drank significantly
      more acetaminophen solution than did those that had no surgery. These data
      suggest that oral self-administration of flavored acetaminophen by rats may be an
      appropriate means to reduce pain.

PMID- 16995648
TI  - Validation of the use of long-term indwelling jugular catheters in a rat model of
      cardiotoxicity.
AB  - Doxorubicin administered to rats induces a dose-dependent cardiomyopathy. Both
      doxorubicin administration and the presence of indwelling catheters have been
      associated with thrombus formation. We sought to determine feasibility of drug
      delivery and degree of thrombogenesis related to long-term indwelling catheter
      use in a cardiotoxicity model. Rats receiving doxorubicin or saline via jugular
      catheters coated with end-point immobilized heparin were compared to rats
      receiving similar treatments via direct jugular intravenous injection (venotomy).
      Onset of cardiotoxicity, defined by reduction in fractional shortening to 45% or
      less, was determined by echocardiography. Thrombogenesis was assessed by
      observation of atrial thrombi and pulmonary emboli as determined by post-mortem
      and histologic examination. Significantly more of the doxorubicin-treated and
      catheterized group (87.5%) developed cardiotoxicity relative to the doxorubicin
      treated-venotomized group (28.6%), as indicated by an earlier and more
      precipitous decline in fractional shortening in the doxorubicin-treated
      catheterized rats. Despite this change, rats from catheterized groups
      demonstrated improved weight maintenance relative to venotomy groups. Although
      the number of pulmonary emboli did not differ significantly between groups, 50%
      of the doxorubicin-treated-catheterized animals developed vegetative
      endocarditis. Despite alteration of the model-induced cardiac disease, we submit
      that the more reliable and early induction of the desired endpoint, in addition
      to improved weight maintenance, represent model refinements. The ease of drug
      delivery with minimal restraint and no anesthesia is an additional and important
      benefit. The development of vegetative endocarditis represents an opportunity to
      study the formation and prevention of this condition.

PMID- 16995649
TI  - Ribosomal RNA sequences of Clostridium piliforme isolated from rodent and rabbit:
      re-examining the phylogeny of the Tyzzer's disease agent and development of a
      diagnostic polymerase chain reaction assay.
AB  - We used polymerase chain reaction (PCR) technology to amplify the 16S rRNA gene,
      the intergenic spacer, and most of the 23S rRNA gene from 6 isolates (2 mice, 1
      hamster, 1 rat, and 2 rabbit isolates) of the Tyzzer's disease agent (Clostridium
      piliforme) and C. colinum. Sequence similarity searches of GenBank identified 45
      closely related bacteria, which we used for phylogenetic analysis by parsimony
      and maximum-likelihood methods using Escherichia coli to root the resulting
      phylogram. Microorganisms identified as C. piliforme form 3 clusters within a
      single clade; the nearest related distinguishable species is C. colinum. Other
      bacterial clades closely related to C. piliforme are clostridia previously
      identified by molecular methods in the bovine, porcine, and human
      gastrointestinal tracts. DNA sequence alignment highlighting sequence differences
      were used to design a rodent and rabbit C. piliforme-specific PCR assay, which
      targets a 639-basepair region at the 3' end of the 16S rRNA gene and the 5' end
      of the intergenic spacer. We used this PCR assay to examine 4 rat fecal samples
      from C. piliformeseropositive rats and reexamine 2 rabbit fecal samples
      previously identified as containing DNA sequences consistent with C. piliforme
      infection by 16S PCR assay. Our new assay did not detect the presence of C.
      piliforme DNA sequences in either the rat or rabbit fecal DNA samples, consistent
      with the absence of clinical disease in the colonies evaluated.

PMID- 16995650
TI  - Evaluation and comparative analysis of a technique for laparoscopic ovariectomy
      in rhesus macaques (Macaca mulatta).
AB  - Surgical ovariectomy is commonly performed to support studies involving the
      rhesus macaque (Macaca mulatta). Traditionally, these procedures have been
      performed via laparotomy. We developed a laparoscopic approach to reduce surgical
      pain, decrease convalescence times, and reduce the total number of animals
      necessary to obtain valuable scientific data in studies requiring repeated intra
      abdominal access in conjunction with ovariectomy. We used our new technique to
      perform laparoscopic ovariectomy on 8 adult female rhesus macaques; 2 additional
      animals underwent ovariectomy via laparotomy; data for these prospective groups
      were compared with retrospective data from conventionally ovariectomized
      macaques. The surgical time (ST; mean +/- standard error) for the laparoscopic
      procedures was 68 +/- 3 min, with a return-to-group time (RTG) of 8 +/- 1 d. In
      comparison, ST for the retrospective group was 54 +/- 3 min, with a mean RTG of
      33 +/- 5 d (range, 15 to 60 d). ST differed significantly between groups. ST for
      the laparoscopic procedure was longer (mean difference, 14 min; 95% confidence
      interval, 6 to 21 min), but laparotomized animals consistently had higher RTG (6
      d for the prospective group [n = 2] and 25 d for the retrospective group [n =
      9]). All study animals had estradiol levels of less than 5.6 pg/ml at 6 mo after
      surgery. We therefore conclude that laparoscopic ovariectomy of rhesus macaques
      is a safe and effective technique that may reduce postoperative recovery times.

PMID- 16995651
TI  - Toxic shock due to Streptococcus pyogenes in a rhesus monkey (Macaca mulatta).
AB  - Recent years have seen a worldwide resurgence in serious infections caused by
      group A streptococci. This group includes Streptococcus pyogenes, one of the most
      common pathogens among children which causes diverse suppurative infections, such
      as pharyngitis, as well as nonsuppurative infections with sequelae, such as
      rheumatoid fever and rheumatic heart disease. S. pyogenes produces several
      superantigen-like erythrogenic toxins, which are believed to be associated with
      pyrogenicity, erythromatous skin reactions, and various immunologic and cytotoxic
      effects. These toxins also can cause myocardial necrosis. In addition, recently
      reported streptococcal infections in obstetric human patients appear to be
      clinically different from classic puerperal sepsis. Here, we report a case of
      spontaneous streptococcal infection in a pregnant female rhesus monkey (Macaca
      mulatta). In addition to lesions consistent with bacteremia and toxic shock, this
      animal had severe cardiac lesions resembling those described in humans with
      rheumatic heart disease. S. pyogenes was isolated from intracardiac blood, liver,
      placenta, and fetal tissues. This isolate also had a unique M protein gene.

PMID- 16995652
TI  - Self-assembly of photochromic diarylethenes with amphiphilic side chains:
      reversible thermal and photochemical control.
AB  - Diarylethene derivatives with hexaethylene glycol side chains were synthesized
      and their self-assembling and photochromic reactivity were investigated. The
      diarylethenes showed photochromism in organic solvents and even in water. The
      aqueous solution of the compounds turned turbid quickly upon heating. The
      clouding behavior was investigated using 1H NMR spectroscopy, dynamic light
      scattering, and absorption spectroscopy. It was revealed that, in the aqueous
      solution, the compounds self-assembled into aggregates, and the aggregates were
      loosened by raising the temperature. The cloud-point temperature of the closed
      ring isomer was 5-7 degrees C lower than that of the open-ring isomer. When
      asymmetric methyl groups were introduced in the amphiphilic side chains, induced
      circular dichroism (ICD) was observed upon irradiation with UV light in water.
      This ICD was explained by the difference in the self-assembling behavior between
      the open- and the closed-ring isomers. It was suggested that the closed-ring
      isomers assembled into a chiral nanostructure.

PMID- 16995653
TI  - Structure-property relationships in push-pull amino/cyanovinyl end-capped
      oligothiophenes: quantum chemical and experimental studies.
AB  - A series of push-pull chromophores built around thiophene-based pi-conjugating
      spacers and bearing various types of amino donors and cyanovinyl acceptors have
      been analyzed by means of UV-vis-NIR, IR, and Raman spectroscopic measurements in
      the solid state as well as in solution. The intramolecular charge transfer (ICT)
      of these pi-conjugated systems has also been tested by analyzing the ability of
      the solute molecules to undergo shifts in their fluorescence emission maxima with
      increasing solvent polarity. These push-pull oligomers also display an attractive
      electrochemical behavior since they generate stable species both upon oxidation
      and reduction. Oxidation mainly involves changes in the electron-rich
      aminooligothienyl half-part of the molecule and leads to the formation of stable
      cations. On the other hand, reduction to radical anions and dianions is mainly
      cyanovinyl-centered but also affects the pi-conjugated electron relay. Density
      functional theory (DFT) calculations have been carried out to help the assignment
      of the most relevant electronic and vibrational features and to derive useful
      information about the molecular structure of these NLO-phores.

PMID- 16995654
TI  - Synthesis of steroid-biaryl ether hybrid macrocycles with high skeletal and side
      chain variability by multiple multicomponent macrocyclization including
      bifunctional building blocks.
AB  - Utilizing the multiple multicomponent macrocyclization including bifunctional
      building blocks (MiB) strategy, a library of nonracemic, nonrepetitive peptoid
      containing steroid-biaryl ether hybrid macrocycles was built. Up to 16 new bonds,
      including those of the macrocyclization, can be formed in one pot simultaneously
      while introducing varied elements of diversity. Functional diversity is generated
      primarily by choosing Ugi-reactive functional building blocks, bearing the
      respective recognition or catalytic motifs. These appear attached to the peptoid
      backbone of the macrocyclic cavity, similar to side chains of amino acids found
      in enzyme active sites. Likewise, skeletal diversity is based on the variation of
      defined bifunctional building blocks which allow the parallel formation of
      macrocyclic cavities that are highly diverse in shape and size and thus
      perspectively in function. This straightforward approach is suitable to generate
      multifunctional macrocycles for applications in catalysis, supramolecular, or
      biological chemistry.

PMID- 16995655
TI  - RCM-mediated synthesis of trifluoromethyl-containing nitrogen heterocycles.
AB  - A ring-closing metathesis mediated pathway to trifluoromethyl-containing
      piperidines is detailed. This involves the development of a synthetic route to a
      new (trifluoromethyl)allylating reagent via a Diels-Alder/retro-Diels-Alder
      strategy, its application in the synthesis of a series of trifluormethyl
      substituted diolefin precursors for ring-closing metathesis, and eventually the
      successful cyclization of these precursor molecules into the corresponding
      functionalized piperidines.

PMID- 16995656
TI  - A simple and efficient method for regioselective and stereoselective synthesis of
      vicinal bromohydrins and alkoxybromides from an olefin.
AB  - A very rapid and efficient method has been developed for the synthesis of vicinal
      bromohydrins and alkoxybromides directly from an olefin without any catalyst. The
      reaction was performed in CH3CN-water (4:1) or alcohol using N,N-dibromo-p
      toluenesulfonamide (TsNBr2) as the brominating agent. Excellent yields and regio-
      and stereoselectivities have been obtained. Bromohydrins are formed
      instantaneously, whereas formation of alkoxybromides takes 30-60 min.

PMID- 16995657
TI  - Controlled synthesis of (S,S)-2,7-diaminosuberic acid: a method for
      regioselective construction of dicarba analogues of multicystine-containing
      peptides.
AB  - A method to facilitate regioselective formation of multiple dicarba isosteres of
      cystine is described. A sequence of ruthenium-catalyzed cross metathesis and
      rhodium-catalyzed hydrogenation of nonproteinaceous allylglycine derivatives has
      been developed to achieve high-yielding and unambiguous formation of
      diaminosuberic acid derivatives. Allylglycine derivatives readily undergo
      ruthenium-catalyzed metathesis and hydrogenation to yield diaminosuberic acid
      derivatives in near quantitative yield. Under the same experimental conditions,
      prenylglycine was found to be inert to both Grubbs' and Wilkinson's catalyzed
      metathesis and hydrogenation, respectively, but was readily activated for
      metathesis via cross metathesis with Z-butene. Subsequent cross metathesis of the
      metathesis-formed crotylglycine derivative, followed by hydrogenation, yielded
      the second diaminosuberic acid derivative in excellent yield.

PMID- 16995658
TI  - C-glycoside clustering on calix[4]arene, adamantane, and benzene scaffolds
      through 1,2,3-triazole linkers.
AB  - A route has been paved toward the preparation of triazole glycocluster libraries
      via the copper(I)-catalyzed modern version of the classical Huisgen 1,3-dipolar
      cycloaddition of azides to alkynes. Up to four 1,4-disubstituted 1,2,3-triazole
      rings bearing carbon-linked glycosyl fragments were constructed on various
      scaffolds via multiple cycloadditions of suitably polyfunctionalized
      calix[4]arene, adamantane, and benzene derivatives with ethynyl and azidomethyl C
      glycosides. Each cycloaddition occurred with high regioselectivity to give
      exclusively the 1,4-disubstituted triazole ring in very high yield up to an
      average value of 98%. The high degree of efficiency of this approach and its wide
      scope constitute a simple and practical means for the attachment of various sugar
      units to polyfunctionalized substrates.

PMID- 16995659
TI  - Synthesis and use of probes to investigate the cryptoregiochemistry of the first
      animal acetylenase.
AB  - Thaumetopoea pityocampa pheromone glands contain an unusual Delta(11) acetylenase
      that produces an alkynoic fatty acid intermediate in the sex pheromone
      biosynthetic pathway of this species. In this article, we describe the synthesis
      and use of the deuterated (Z)-11-hexadecenoic acid probes required to decipher
      the cryptoregiochemistry of this enzyme. The label in the olefinic bonds was
      introduced by Wittig reaction between the appropriate deuterated reagents.
      Besides the vinyl deuterium atoms, for reliable GC-MS analyses these compounds
      bear a tetradeuterium tag, which was introduced by deuteration of an alkyne
      intermediate in the presence of the Wilkinson catalyst. Pheromone gland
      metabolization studies of these probes provided experimental evidence that the
      transformation of (Z)-11-hexadecenoic acid into 11-hexadecynoic acid by the
      Delta(11) acetylenase takes place by a stepwise mechanism, in which a significant
      perturbation of the strong vinyl C11-H bond occurs prior to a fast elimination of
      the vinyl hydrogen at C-12.

PMID- 16995660
TI  - Facile synthesis and detailed characterization of a new ferrocenyl uracil peptide
      nucleic acid monomer.
AB  - A new ferrocenyl uracil peptide nucleic acid (PNA) monomer, tert-butyl-2-(N-(2
      (((9H-floren-9-yl)methoxy)carbonylamino)ethyl)-2-(5-(N-ferrocenylmethylbenzamido)
      2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetate (1), has been
      successfully prepared in good yield by a procedure involving the one-pot reaction
      of the key synthon, 5-(ferrocenylmethylamino)pyrimidine-2,4(1H,3H)-dione (4),
      itself prepared from the reaction of (ferrocenylmethyl)trimethylammonium iodide
      and 5-aminouracil, with benzoyl chloride followed by ethyl bromoacetate. After
      hydrolysis of the ester, the acid was coupled with a protected PNA backbone to
      generate 1. NMR spectroscopy showed that 1 hydrogen bonds 9-ethyladenine (EA) in
      a 1:1 mixture of CD3CN:CDCl3 with an association constant Ka of 70 M(-1) at 30
      degrees C. This value is comparable with those observed for model receptors and
      shows that the ferrocenyl moiety of 1 does not hinder the hydrogen bonding of our
      new PNA monomer to the complementary DNA base or if it does, not significantly. 1
      is oxidized to 1+ with a reversible potential of +538 mV vs the DMFc(0/+)
      (decamethylferrocene) couple under voltammetric conditions in a 1:1 mixture of
      CH3CN:CHCl3 (0.1 M Bu4NPF6). For this reversible process, a slightly larger
      diffusion coefficient of 4.2 x 10(-6) cm(2).s(-1) than usually found for these
      compounds was determined from these electrochemical studies, which should be
      analytically useful as it will readily afford submicromolar voltammetric
      detection limits.

PMID- 16995661
TI  - Access to piperidine imino-C-glycosides via stereoselective thiazole-based
      aminohomologation of pyranoses.
AB  - The access to piperidine homoazasugars (dideoxyiminoheptitols) from pyranoses via
      formal one-carbon chain elongation and exchange of the ring oxygen with the NH
      group is described. The key process involves the stereoselective addition of 2
      thiazolylmagnesium bromide to an N-glycosylhydroxylamine, i.e., a hidden open
      chain sugar nitrone. The N-thiazolylalkylhydroxylamine formed in this way is
      reduced to amine, and this transformed into a substituted piperidine via
      intramolecular cyclization by an S(N)2 process. Cleavage of the thiazole residue
      attached to C2 of the piperidine ring reveals the formyl group, and this is
      reduced to hydroxymethyl to give the target homoazasugar. A collection of six
      stereodiversified compounds with free OH and NH groups and isolated as
      hydrochlorides has been prepared.

PMID- 16995662
TI  - Practical formal total syntheses of the homocamptothecin derivative and
      anticancer agent diflomotecan via asymmetric acetate aldol additions to pyridine
      ketone substrates.
AB  - Two practical, efficient, and scalable asymmetric routes to DE ring fragment 7, a
      key building block in the synthesis of the homocamptothecin derivative
      diflomotecan 4, are described. The "acetal route" starts from 2-chloro-4
      cyanopyridine 8 and represents an enantioselective and optimized modification of
      the original racemic discovery chemistry synthesis. The inefficient optical
      resolution procedure was replaced by an efficient asymmetric acetate aldol
      addition (dr 87:13) to a ketone substrate as the key step generating the (R)
      configured quaternary stereocenter with high stereoselectivity. 7 was finally
      obtained in 8.9% overall yield (er 99.95:0.05) over nine steps, avoiding
      chromatographic purifications and comparing favorably with the initial procedure.
      In the related "amide route" starting from 2-chloroisonicotinic acid 41, a
      secondary amide directing group was used to facilitate the ortho lithiation of
      the pyridine 3-position. The key step of this protocol again consists of a
      practical asymmetric acetate aldol addition (dr = 87:13). The DE ring building
      block 7 was thus obtained in 11.1% overall yield (er > 99.95:0.05) over nine
      steps requiring only one chromatographic purification.

PMID- 16995663
TI  - The synthesis of N,O-ferrocenyl pyrrolidine-containing ligands and their
      application in the diethyl- and diphenylzinc addition to aromatic aldehydes.
AB  - A facile route to a series of planar chiral N,O-ferrocenyl pyrrolidine-containing
      ligands with varying substituents at the nitrogen and oxygen donor atoms is
      described. The oxygen donor atom was introduced via a diastereoselective ortho
      metalation of N-methylpyrrolidinyl and N-allylpyrrolidinyl ferrocene
      intermediates and was quenched with various ketones. The nitrogen substituent was
      varied through deallylation and subsequent derivatization of a secondary
      pyrrolidine. The efficacy of these novel ligands was investigated in the
      enantioselective addition of diethylzinc and diphenylzinc to aromatic aldehydes.
      The ligands proved highly effective in the diethylzinc addition to benzaldehyde
      that resulted in high yields of up to 99% and enantioselectivities (ee's) of up
      to 95%. The role of planar chirality was explored and the results indicated that
      the planar chirality, and not the central chirality, of the ferrocenyl ligands
      was the dominant stereo-controlling element. Employment of a mixed ethyl
      phenylzinc reagent in the phenylation of aromatic aldehydes led to a mixture of
      the two additional products, and the phenylated product was obtained in up to 37%
      ee.

PMID- 16995664
TI  - Liquid-crystalline bisadducts of [60]fullerene.
AB  - A second-generation cyanobiphenyl-based dendrimer was used as a liquid
      crystalline promoter to synthesize mesomorphic bisadducts of [60]fullerene.
      Liquid-crystalline trans-2, trans-3, and equatorial bisadducts were obtained by
      condensation of the liquid-crystalline promoter, which carries a carboxylic acid
      function, with the corresponding bisaminofullerene derivatives. A monoadduct of
      fullerene was also prepared for comparative purposes. All the compounds gave rise
      to smectic A phases. An additional mesophase, which could not be identified, was
      observed for the trans-2 derivative. The supramolecular organization of the
      monoadduct derivative is governed by steric constraints. Indeed, for efficient
      space filling, adequacy between the cross-sectional areas of fullerene
      (approximately 100 A(2)) and of the mesogenic groups (approximately 22-25 A(2)
      per mesogenic group) is required. As a consequence, the monoadduct forms a
      bilayered smectic A phase. The supramolecular organization of the bisadducts is
      essentially governed by the nature and structure of the mesogenic groups and
      dendritic core. Therefore, the bisadducts form monolayered smectic A phases. The
      title compounds are promising supramolecular materials as they combine the self
      organizing behavior of liquid crystals with the properties of fullerene.

PMID- 16995665
TI  - 7-Pyridylindoles: synthesis, structure, and properties.
AB  - A series of three isomeric 7-pyridylindoles (7-PIs) are prepared where the
      pyridine attachment is through C2, C3, or C4. These systems are prepared by a
      combination of the Bartoli reaction and the Stille coupling with an appropriate
      pyridyl stannane. By treatment with CH(3)I, the 7-PIs can be converted to their
      pyridinium salts. Deprotonation at the NH of these salts leads to a zwitterion
      which, in the 4-pyridyl system, also exists as a neutral isomer. The
      photophysical and NMR properties of these systems are discussed. All three
      pyridylindoles are analyzed by X-ray crystallography and shown to exist in
      different states of aggregation dictated by the formation of intra- and
      intermolecular H-bonds.

PMID- 16995666
TI  - Design, synthesis, and structure--activity relationships for chimeric inhibitors
      of Hsp90.
AB  - Inhibition of the 90 kDa heat shock protein (Hsp90) family of molecular
      chaperones represents a promising new chemotherapeutic approach toward the
      treatment of several cancers. Previous studies have demonstrated that the natural
      products, radicicol and geldanamycin, are potent inhibitors of the Hsp90 N
      terminal ATP binding site. The cocrystal structures of these molecules bound to
      Hsp90 have been determined, and through molecular modeling and superimposition of
      these ligands, hybrids of radicicol and geldanamycin have been designed. A series
      of macrocylic chimeras of radicicol and geldanamycin and the corresponding seco
      agents have been prepared and evaluated for both antiproliferative activity and
      their ability to induce Hsp90-dependent client protein degradation.

PMID- 16995667
TI  - Dynamic kinetic resolution of benzoins by lipase-metal combo catalysis.
AB  - The synthesis of some noncommercial racemic 1,2-diaryl-2-hydroxyethanones
      (benzoins) is described, optimizing the previously reported methodologies. In a
      further step, the kinetic resolution of these substrates is reported, obtaining
      conversions of around 50% and ee(p) higher than 99% in very short reaction times.
      As enzymatic catalyst, after screening of several enzymes, the lipase TL (from
      Pseudomonas stutzeri) was the most efficient, working in an organic solvent with
      a very low log P value, such as THF. Finally, the dynamic-kinetic resolution of
      different benzoins using a lipase-ruthenium-catalyzed transesterification in
      organic solvents is described for the first time, obtaining conversions up to 90%
      maintaining the excellent enantioselectivity in all cases.

PMID- 16995668
TI  - Stereodynamics of 1-(methylsulfonyl)-3,5-bis(trifluoromethylsulfonyl)-1,3,5
      triazinane: experimental and theoretical analysis.
AB  - Dynamic NMR of 1-(methylsulfonyl)-3,5-bis(trifluoromethylsulfonyl)-1,3,5
      triazinane reveals the existence of three conformers and two dynamic processes:
      ring inversion and rotation about the N-S bond, both processes having DeltaG(++)
      = 13.5 kcal/mol. An unprecedented large reverse Perlin effect (J(CHax) > J(CHeq))
      was found experimentally and calculated theoretically.

PMID- 16995669
TI  - Absolute stereochemistry of fungal beauveriolide III and ACAT inhibitory activity
      of four stereoisomers.
AB  - Fungal beauveriolide III (BeauIII, 1b), a cyclodepsipeptide inhibiting acyl
      CoA:cholesterol acyltransferase (ACAT) and showing antiatherogenic activity in
      mouse models, consists of L-Phe, L-Ala, D-allo-Ile, and 3-hydroxy-4
      methyloctanoic acid (HMA) moieties, but the stereochemistry of the HMA part has
      not until now been fully defined. To determine it, four HMA stereoisomers were
      synthesized and labeled with (S)-(+)-2-(anthracene-2,3-dicarboximido)-1-propyl
      trifluoromethane sulfonate (AP-OTf), a chiral fluorescent reagent. The
      derivatives were separated by HPLC and compared with the natural HMA derivative,
      which was thereby identified as (3S,4S)HMA in BeauIII. Furthermore, the four
      beauveriolide III isomers ((3S,4S)BeauIII (23a), (3R,4R)BeauIII (23b),
      (3R,4S)BeauIII (23c), and (3S,4R)BeauIII (23d)) were synthesized, and it was
      shown that all the spectral data for 23a were identical with those for natural
      1b. Isomers 23a and 23d showed potent inhibitory activity of lipid droplet
      accumulation in macrophages, while the other two isomers caused weak inhibition.
      Thus, the 3S configuration of BeauIII is important for this activity.
      Furthermore, 23a and 23d showed rather specific inhibition against the ACAT1
      isozyme.

PMID- 16995670
TI  - Kinetic and theoretical studies on the mechanism of intramolecular catalysis in
      phenyl ester hydrolysis.
AB  - The kinetic study of the hydrolysis reaction of Z-substituted phenyl hydrogen
      maleates (Z = H, m-CH3, p-CH3, m-Cl, p-Cl and m-CN) was carried out in aqueous
      solution, and the results were complemented with theoretical studies. Under some
      experimental conditions, two kinetic processes were observed. One of them was
      ascribed to maleic anhydride formation and the other to the anhydride hydrolysis.
      The Bronsted-type plot for the leaving-group dependence was linear with slope
      beta(lg) = -1. The experimental results are consistent with a mechanism that
      involves significant bond breaking in the rate-limiting transition state
      (alpha(lg) = 0.64). Theoretical results for the reaction in the gas phase showed
      an excellent Bronsted-type dependence with a beta(lg) of -1.03. A tetrahedral
      intermediate (TI) could not be found through DFT gas-phase studies (B3LYP/6
      311+G*). Calculations carried out within a continuous solvation model or with
      discrete water molecules failed to find a stable TI. With both models, a flat
      region on the potential-energy surface is found and a tight optimization of the
      structures led back to starting materials. The theoretical results do not discard
      the possible existence of an unstable intermediate on the free-energy surface,
      but the analysis of the whole body of results compared with other acyl transfer
      reactions lead us to suggest that an enforced concerted mechanism is the most
      appropriate to describe these reactions.

PMID- 16995671
TI  - Nitroxide bound beta-cyclodextrin: is there an inclusion complex?
AB  - 236CDTIPNO, a derivative of the persistent free radical TIPNO (1,1-dimethylethyl
      2-methyl-1-phenylpropyl nitroxide) covalently bound to a permethylated-beta
      cyclodextrin, was prepared. Self-association of 236CDTIPNO in water was proved by
      solvent- and competition-dependent EPR spectroscopy experiments with 2,6-di-O-Me
      beta-cyclodextrin (DIMEB) and permethylated-beta-cyclodextrin (TRIMEB) as
      external hosts competing for accommodation of the TIPNO moiety. Temperature
      dependent EPR spectra were simulated with a novel two-dimensional (field
      temperature) EPR simulation program that afforded a full determination of the
      thermodynamic parameters characterizing the rate constants of the self-inclusion
      reaction derived from Arrhenius and Eyring models. This method allows separating
      the line broadening effects due to relaxation from a chemical exchange, even if
      only the fast exchange regime is accessible experimentally. The activation
      parameters for the forward and backward steps were consistent with an equilibrium
      between a nonassociated form and a weakly associated form, with activation free
      enthalpies for each reaction of around 34 kJ.mol(-)(1).

PMID- 16995672
TI  - cis-Tetrahydrofuran-3,4-diol structure as a key skeleton of new protecting groups
      removable by self-cyclization under oxidative conditions.
AB  - A variety of carbonate-type acyl groups having a cis-tetrahydrofuran-3,4-diol
      (1,4-anhydroerythritol) backbone structure and a TrS or MMTrS group have been
      examined as new "protected" protecting groups of the 5'-hydroxyl group of
      nucleosides. These acyl groups were designed in a manner where they could be
      deprotected by I(2)-promoted removal of the TrS or MMTrS group followed by self
      cyclization involving an intramolecular attack of the once-generated neighboring
      hydroxyl group on the acyl carbon. It turned out that these acyl groups could be
      introduced into the 5'-hydroxyl group of a 3'-O-protected thymidine derivative by
      use of the corresponding acyl imidazolides or 4-nitrophenyl esters as well as by
      reaction with carbonyldiimidazole or 4-nitrophenyl chloroformate. Among the acyl
      groups tested, it was found that the CTFOC group could be easily introduced into
      the 5'-hydroxyl group of 3'-masked deoxyribonucleoside derivatives and rapidly
      removed under mild conditions using iodine.

PMID- 16995673
TI  - Topology-driven physicochemical properties of pi-electron systems. 1. Does the
      Clar rule work in cyclic pi-electron systems with the intramolecular hydrogen or
      lithium bond?
AB  - The Clar model predicting stability and electron distribution in benzenoid
      hydrocarbons seems to be also a good predictor for related properties in lithium
      o-acylphenolates and to a lesser extent in the phenols themselves. This
      conclusion is based on analysis of geometry changes in the analogues of
      naphthalene, phenanthrene, anthracene, and triphenylene, where benzene rings are
      systematically replaced with a quasi-ring formed as a beta-ketoenol or beta
      ketoenolate complex with a lithium cation, i.e., where CH-CH-CH fragments are
      replaced with O...Li...O or O...H...O fragments. These systems were optimized at
      the MP2/6-31G(2d,p) level of theory. The energy of bond separation reactions in
      line with aromaticity indices HOMA and NICSs supported the above statement.

PMID- 16995674
TI  - Efficient trans-selectivity in the cyclocondensation of (S)-2-[2-(p
      tolylsulfinyl)phenyl]acetaldehyde with activated dienes catalyzed by Yb(OTf)3.
AB  - Reactions of (S)-2-[2-(p-tolylsulfinyl)phenyl]acetaldehyde 1 with Danishefsky's
      and related dienes took place in the presence of Yb(OTf)3 in a completely
      stereoselective manner, mediated by a remote sulfinyl group (1,5-asymmetric
      induction), to afford the corresponding 2,3-dihydro-4H-pyran-4-ones. These
      reactions followed a stepwise mechanism, as was corroborated by isolation of the
      corresponding intermediates, with a high level of trans-selectivity for 4-methyl
      substituted dienes. Treatment of the adducts with Raney Ni provided concomitant
      cleavage of the C-S bond and reduction of the conjugated carbonyl grouping.

PMID- 16995675
TI  - Efficient synthesis of 1-azadienes derived from alpha-aminoesters. Regioselective
      preparation of alpha-dehydroamino acids, vinylglycines, and alpha-amino acids.
AB  - An efficient synthesis of 1-azadienes derived from alpha-aminoesters is achieved
      through an aza-Wittig reaction of phosphazenes with beta,gamma-unsaturated alpha
      ketoesters. Regioselective 1,2-reduction of these functionalized 1-azadienes
      affords vinylglycine derivatives, while conjugative 1,4-reduction gives alpha
      dehydroamino acid compounds. Reduction of both the carbon-carbon and the imine
      carbon-nitrogen double bonds leads to the formation of alpha-amino acid
      derivatives.

PMID- 16995676
TI  - Preparation, isolation, and characterization of Nalpha-Fmoc-peptide isocyanates:
      solution synthesis of oligo-alpha-peptidyl ureas.
AB  - The N(alpha)-Fmoc-peptide isocyanates 3a-q, 4a-c, and 5a-c were prepared by the
      Curtius rearrangement of N(alpha)-Fmoc-peptide acid azides in toluene under
      thermal, microwave, and ultrasonic conditions. All the N(alpha)-Fmoc-oligo
      peptide isocyanates made were isolated as stable crystalline solids with 71 to
      94% yield and were fully characterized by 1H NMR, 13C NMR, and mass spectroscopy.
      Their utility for the synthesis of oligo-alpha-peptidyl ureas 7a-f and 8a-c by
      the divergent coupling approach was demonstrated. The coupling of N(alpha)-Fmoc
      dipeptide isocyanates with amino acid ester or with N,O-bis(trimethylsilyl)amino
      acids resulted in N(alpha)-Fmoc-tripeptidyl urea ester and acids containing one
      each of peptide bond and urea bond. The divergent approach is extended to the
      synthesis of tetrapeptidyl ureas by the 2 + 2 strategy using bis-TMS-peptide acid
      as an amino component. To incorporate urea bonds in adjacent positions, N(alpha)
      Fmoc-peptidyl urea isocyanates 9a-d were prepared and employed in the synthesis
      of three tetrapeptidyl ureas 10a-b and 11 containing one peptide bond and two
      urea bonds in series from the N-terminal end. The protocol was then employed for
      the synthesis of five urea analogues 13-15, 18, and 21 of [Leu5]enkephalin
      containing urea bonds at the 2, 3, 4 positions as well as at the 2, 4 and 2, 3, 4
      positions. The analogue 2l was made by the convergent synthesis by the N --> C
      terminal chain extension. Finally, two urea analogues 22 and 23 of repeat units
      of bioelasto polymers, namely Val-Pro-Gly-Val-Gly-OH and Pro-Gly-Val-Gly-Val-OH,
      were synthesized incorporating the urea bond by the concomitant isocyanate
      generation and urea bond formation under thermal conditions.

PMID- 16995678
TI  - Aminolysis of Y-substituted phenyl diphenylphosphinates and benzoates: effect of
      modification of electrophilic center from C=O to P=O.
AB  - The effect of modification of the electrophilic center from C=O to P=O on
      reactivity and reaction mechanism has been investigated for aminolysis of Y
      substituted phenyl diphenylphosphinates (1a-j) and benzoates (2a-i). The
      phosphinates 1a-j are less reactive than the benzoates 2a-i. The reactions of 2,4
      dinitrophenyl diphenylphosphinate (1a) with alicyclic secondary amines resulted
      in a linear Bronsted-type plot with a beta(nuc) value of 0.38, while the
      corresponding reactions of 2,4-dinitrophenyl benzoate (2a) yielded a curved
      Bronsted-type plot. Similarly, a linear Bronsted-type plot with a beta(lg) value
      of -0.66 was obtained for the reactions of 1a-j with piperidine, while the
      corresponding reactions of 2a-i gave a curved Bronsted-type plot. The linear
      Bronsted-type plots for the reactions of 1a-j have been taken as evidence for a
      concerted mechanism, while the curved Bronsted-type plots for the reactions of 2a
      i have been suggested to indicate a change in the rate-determining step of a
      stepwise mechanism. The Hammett plot for the reactions of 1b-j exhibited a poor
      correlation with sigma(-) constants (R(2) = 0.962) but slightly better
      correlation with sigma(o) (R(2) = 0.986). However, the Yukawa-Tsuno plot for the
      same reactions resulted in an excellent correlation (R(2) = 0.9993) with an r
      value of 0.30. The aminolysis of 1a-j has been suggested to proceed through a
      concerted mechanism with an early transition state on the basis of the small
      beta(nuc) and small r values.

PMID- 16995677
TI  - Concise synthesis of guanidine-containing heterocycles using the Biginelli
      reaction.
AB  - Two general methods for the synthesis of 2-imino-5-carboxy-3,4-dihydropyrimidines
      were developed using the three-component Biginelli reaction. The first method
      utilizes pyrazole carboxamidine, a beta-ketoester, and an aldehyde in an initial
      Biginelli reaction. After Boc protection, these products undergo aminolysis and
      acidic deprotection to generate 2-imino-5-carboxy-3,4-dihydropyrimidines in a
      four-step sequence. The second method utilizes a triazone-protected guanidine, a
      beta-ketoester, and an aldehyde in a Biginelli reaction. Acidic cleavage of the
      triazone yields 2-imino-5-carboxy-3,4-dihydropyrimidines in a two-step sequence.
      We also describe the further elaboration of several of these products using a
      tethered Biginelli reaction to give triazaacenaphthalene structures similar to
      those found in crambescidin and batzelladine alkaloids.

PMID- 16995679
TI  - Synthesis of enantiopure pyrrolidine-derived peptidomimetics and oligo-beta
      peptides via nucleophilic ring-opening of beta-lactams.
AB  - The synthesis of the two enantiomers of pyrrolidine-derived spiro beta-lactams by
      resolution with D- and L-Boc phenylalanine is described. The potential of these
      optically active spiro beta-lactams on the synthesis of peptidomimetics as
      analogues of melanostatin is evaluated. Theoretical studies of several models, at
      the Becke3LYP/6-31+G* level of theory, together with previous experimental
      evidences from our group, gathered by NMR, allow us to design structures that can
      efficiently mimic some biologically active peptide-type molecules. On the other
      hand, the spiro beta-lactams have shown their utility in the preparation of beta
      peptides. As an example, a homo-tetra-beta-peptide was synthesized. This research
      will continue in the future in order to obtain higher peptides with potential
      biological activity.

PMID- 16995680
TI  - Analogues of a locked nucleic acid with three-carbon 2',4'-linkages: synthesis by
      ring-closing metathesis and influence on nucleic acid duplex stability and
      structure.
AB  - Two bicyclic 2'-deoxynucleoside analogues containing a saturated and an
      unsaturated three-carbon 2',4'-linkage, respectively, have been synthesized using
      a ring-closing metathesis-based linear strategy starting from uridine. Both
      analogues have been incorporated into oligodeoxynucleotide sequences and
      increased the stability of DNA:RNA hybrid duplexes (DeltaT(m) approximately 2.5
      5.0 degrees C per modification) and decreased the stability of dsDNA duplexes
      (DeltaT(m) approximately 2.5-1.0 degrees C per modification). CD spectroscopy
      revealed that the bicyclic nucleosides induced formation of A-type-like duplexes
      albeit to a lesser degree than found for locked nucleic acid (LNA) monomers. From
      the CD data and UV melting analysis, we propose that the 2'-oxygen atom of the
      bicyclic moiety is essential for the formation of stabilized A-type-like dsDNA
      but not for the formation of a stabilized A-type DNA:RNA hybrid.

PMID- 16995681
TI  - De novo synthesis of 2-substituted syn-1,3-diols via an iterative asymmetric
      hydration strategy.
AB  - The enantioselective syntheses of several protected 4-substituted syn-3,5
      dihydroxy carboxylic esters have been achieved from the corresponding achiral
      (E,E)- or (E,Z)-1,3-dienoates. The route relies upon an enantio- and
      regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to
      form gamma-substituted delta-hydroxy-1-enoates. The resulting delta-hydroxy-1
      enoates are subsequently converted into benzylidene-protected 4-substituted syn
      3,5-dihydroxy carboxylic esters in one step. The benzylidene-protected 3,5
      dihydroxy carboxylic esters are produced in good overall yields (20-54%) and high
      enantiomeric excess (73-97% ee).

PMID- 16995682
TI  - Insight on the NMR study of supramolecular gels and its application to monitor
      molecular recognition on self-assembled fibers.
AB  - The 1H NMR study of supramolecular gels formed by two organogelators derived from
      valine is described. The analysis of the variation of chemical shift values and
      relaxation times in the gel samples reveals that in these systems only discrete
      species are observed by 1H NMR. The reduced T2 values and negative NOEs that are
      measured upon gel formation can be ascribed to an exchange between discrete
      organogelator species and the gel network. This process is found to be fast in
      the time scale of 1H NMR relaxation and slow in the NMR observation frequency
      time scale. It is shown here that other molecules, aside from the gelator itself,
      can interact with the gel network and this process can be monitored easily by
      measurement of relaxation times. As a proof of principle, the selective
      interaction of 2,2'-bis(hydroxymethyl)biphenyl over diphenylmethane with the self
      assembled fibers formed by one of the gelators in benzene is described.

PMID- 16995684
TI  - (S,S)-(+)-Pseudoephedrine as chiral auxiliary in asymmetric conjugate addition
      and tandem conjugate addition/alpha-alkylation reactions.
AB  - Organolithium reagents undergo highly regio- and diastereoselective 1,4-addition
      to (S,S)-(+)-pseudoephedrine enamides furnishing the corresponding beta-alkyl
      substituted adducts in excellent yields and diastereoselectivities. In addition,
      the intermediate lithium enolates generated after the conjugate addition step
      undergo a highly diastereoselective alkylation reaction, furnishing alpha,beta
      dialkyl-substituted amides in high yields. The obtained adducts have been
      converted into chiral nonracemic beta-alkyl- and alpha,beta-dialkyl-substituted
      carboxylic acids and gamma-alkyl- and beta,gamma-dialkyl-substituted alcohols
      using very simple and high-yielding procedures.

PMID- 16995683
TI  - Effect of the phosphoryl substituent in the linear nitrone on the spin trapping
      of superoxide radical and the stability of the superoxide adduct: combined
      experimental and theoretical studies.
AB  - A new phosphorylated linear nitrone N-(4-hydroxybenzyliene)-1-diethoxyphosphoryl
      1-methylethylamine N-oxide (4-HOPPN) was synthesized, and its X-ray structure was
      determined. The spin trapping ability of various kinds of free radicals by 4
      HOPPN was evaluated. Kinetic study of decay of the superoxide spin adduct (4
      HOPPN-OOH) shows the half-life time of 8.8 min. On the basis of the X-ray
      structural coordinates, theoretical analyses using density functional theory
      (DFT) calculations at the B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) level were performed
      on spin-trapping reactions of superoxide radical with 4-HOPPN and PBN and three
      possible decay routes for their corresponding superoxide adducts. The comparative
      calculations on the spin-trapping reactions with superoxide radical predicted
      that both spin traps share an identical reaction type and have comparable potency
      when spin trapping superoxide radical. Analysis of the optimized geometries of 4
      HOPPN-OOH and PBN-OOH reveals that an introduction of the phosphoryl group can
      efficiently stabilize the spin adduct through the intramolecular H-bonds, the
      intramolecular nonbonding attractive interactions, as well as the bulky steric
      protection. Examination of the decomposition thermodynamics of 4-HOPPN-OOH and
      PBN-OOH further supports the stabilizing role of the phosphoryl group to a linear
      phosphorylated spin adduct.

PMID- 16995685
TI  - Regiospecific and highly stereoselective coupling of 6-(substituted-imidazol-1
      yl)purines with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-erythro-pentofuranosyl
      chloride. Sodium-salt glycosylation in binary solvent mixtures: improved
      synthesis of cladribine.
AB  - Glycosylation of 6-(substituted-imidazol-1-yl)purine sodium salts with 2-deoxy
      3,5-di-O-(p-toluoyl)-alpha-D-erythro-pentofuranosyl chloride proceeds with
      regiospecific formation of the N9 isomers. Base substrates with lipophilic
      substituents on the C6-linked imidazole moiety are more soluble in organic
      solvents, and the solubility is further increased with binary solvent mixtures.
      Selective solvation also diminishes the extent of anomerization of the
      chlorosugar. Stirred reaction mixtures of the modified-purine sodium salts
      generated in a polar solvent and cooled solutions of the protected 2-deoxysugar
      chloride in a nonpolar solvent give 2'-deoxynucleoside derivatives with N9
      regiochemistry and enhanced beta/alpha configuration ratios. Application of the
      binary-solvent methodology with 2-chloro-6-(substituted-imidazol-1-yl)purine
      salts in cold acetonitrile and the chlorosugar in cold dichloromethane gives
      essentially quantitative yields of the N9 isomers of beta-anomeric 2'
      deoxynucleoside intermediates. Direct ammonolysis (NH(3)/MeOH) of such
      intermediates or benzylation of the imidazole ring followed by milder ammonolysis
      of the imidazolium salt gives high yields of the clinical anticancer drug
      cladribine (2-chloro-2'-deoxyadenosine).

PMID- 16995686
TI  - A simple, two-step, site-specific preparation of fluorinated naphthalene and
      phenanthrene derivatives from fluorobromo-substituted alkenes.
AB  - A facile two-step procedure for the site-specific preparation of fluorinated
      naphthalene and phenanthrene derivatives is described. The Sonogashira reaction
      of bromofluoro-substituted alkenes with terminal alkynes, followed by base
      catalyzed cyclization in refluxing N-methyl-2-pyrrolidinone (NMP), affords the
      corresponding fluorinated naphthalene and phenanthrene derivatives in good
      yields.

PMID- 16995687
TI  - Effect of structure in benzaldehyde oximes on the formation of aldehydes and
      nitriles under photoinduced electron-transfer conditions.
AB  - The mechanistic aspects of the photosensitized reactions of a series of
      benzaldehyde oximes (1a-o) were studied by steady-state (product studies) and
      laser flash photolysis methods. Nanosecond laser flash photolysis studies have
      shown that the reaction of the oxime with triplet chloranil (3CA) proceeds via an
      electron-transfer mechanism provided the free energy for electron transfer
      (DeltaG(ET)) is favorable; typically, the oxidation potential of the oxime should
      be below 2.0 V. Substituted benzaldehyde oximes with oxidation potentials greater
      than 2.0 V quench 3CA at rates that are independent of the substituent and the
      oxidation potential. The most likely mechanism under these conditions is a
      hydrogen atom transfer mechanism as this reaction should be dependent on the O-H
      bond strength only, which is virtually the same for all oximes. Product studies
      have shown that aldoximes react to give both the corresponding aldehyde and the
      nitrile. The important intermediate in the aldehyde pathway is the iminoxyl
      radical, which is formed via an electron transfer-proton transfer (ET-PT)
      sequence (for oximes with low oxidation potentials) or via a hydrogen atom
      transfer (HAT) pathway (for oximes with larger oxidation potentials). The
      nitriles are proposed to result from intermediate iminoyl radicals, which can be
      formed via direct hydrogen atom abstraction or via an electron-transfer-proton
      transfer sequence. The experimental data seems to support the direct hydrogen
      atom abstraction as evidenced by the break in linearity in the plot of the
      quenching rates against the oxidation potential, which suggests a change in
      mechanism. The nitrile product is favored when electron-accepting substituents
      are present on the benzene ring of the benzaldehyde oximes or when the hydroxyl
      hydrogen atom is unavailable for abstraction. The latter is the case in pyridine
      2-carboxaldoxime (2), where a strong intramolecular hydrogen bond is formed.
      Other molecules that form weaker intramolecular hydrogen bonds such as 2
      furaldehyde oxime (3) and thiophene-2-carboxaldoxime (4) tend to yield increasing
      amounts of aldehyde.

PMID- 16995688
TI  - Synthesis of new 2-vinylation products of indole via a Michael-type addition
      reaction with dimethyl acetylenedicarboxylate and their Diels-Alder reactivity as
      precursors of new carbazoles.
AB  - Reaction of 4,7-dihydroindole and dimethyl acetylenedicarboxylate provided a
      convenient route to functionalized 2-vinylindoles. Diels-Alder reactions of the 2
      vinylindoles with naphthoquinone, p-benzoquinone, 1,2-dicyano-4,5
      dichloroquinone, N-phenyltriazolinedione, and tetracyanoethylene were
      investigated to give [c]annelated 1,2-dihydro, 1,2,3,4-tetrahydro, and fully
      aromatized carbazoles. The structure and formation mechanism of both 2
      vinylindoles and their cycloadduct are discussed.

PMID- 16995689
TI  - Oxaza adamantyl cannabinoids. A new class of cannabinoid receptor probes.
AB  - The preparation of C3 oxaza adamantyl cannabinoids has been described starting
      from phloroglucinol. Straightforward manipulations of the aromatic ring lead to a
      bromononaflate that is a benzyne precursor and that serves as a common
      intermediate for the synthesis of diverse C3-substituted tricyclic cannabinoids.
      Generation of the benzyne in the presence of an oxaza adamantyl amide anion
      results in efficient and regiospecific addition to C3 of the aromatic ring. This
      represents an attractive strategy for the synthesis of classical tricyclic
      cannabinoids that bear a modified aromatic appendage. The oxaza adamantyl
      cannabinoids that have been prepared represent a new class of ligands for the CB1
      and CB2 receptors.

PMID- 16995690
TI  - New facile tandem route to oxo- and thioxo[1,2,4]triazolo[1,5-a]pyridinium salts.
AB  - 2-Arylsulfanyl- and benzylsulfanylpyridinium N-arylimides (2), easily available
      from tetrazolo[1,5-b]pyridinium salts (1), participate in 1,3-dipolar
      cycloaddition with aryl isothiocyanates and aryl isocyanates to result in
      formation of fused thioxo- and oxo[1,2,4]triazolium salts (5 and 12),
      respectively. This transformation is interpreted as a regular 1,3-cycloaddition
      followed by spontaneous elimination of the aryl- or benzylsulfanyl group.
      Formation of these triazolium salts can be followed--under appropriate reaction
      conditions--by ring-opening reactions to afford some new triazolyldienes (6).
      Recognition of the intermediate participation of the thiolate anion along the
      pathway 1 --> 5 allowed elaboration of a simple procedure to 5 implying a tandem
      reaction sequence.

PMID- 16995691
TI  - Rhenium-catalyzed 1,3-isomerization of allylic alcohols: scope and chirality
      transfer.
AB  - The scope of the triphenylsilyl perrhennate (O3ReOSiPh3, 1) catalyzed 1,3
      isomerization of allylic alcohols has been thoroughly explored. It was found to
      be effective for a wide variety of secondary and tertiary allylic alcohol
      substrates bearing aryl, alkyl, and cyano substituents. Two general reaction
      types were found which gave high levels of product selectivity: those driven by
      formation of an extended conjugated system and those driven by selective
      silylation of a particular isomer. The efficiency of chirality transfer with
      various substrates was investigated, and conditions were found in which secondary
      and tertiary allylic alcohols could be formed with high levels of
      enantioselectivity. Consideration of selectivity trends with respect to the
      nature of the substituents around the allylic system revealed that this is a
      reliable and predictable method for allylic alcohol synthesis.

PMID- 16995692
TI  - Palladium-catalyzed, modular synthesis of highly functionalized indoles and
      tryptophans by direct annulation of substituted o-haloanilines and aldehydes.
AB  - One-pot synthesis of indoles by a palladium-catalyzed annulation of ortho
      haloanilines and aldehydes has been developed. Coupling of ortho-iodoaniline with
      aldehyde is realized under mild ligandless conditions [Pd(OAc)2, DABCO, DMF, 85
      degrees C], whereas X-Phos is found to be the ligand of choice for coupling
      reactions involving ortho-chloroanilines/ortho-bromoanilines and aldehydes. A
      variety of ortho-haloanilines with different electronic properties are suitable
      substrates, and aldehydes including chiral ones participated in this reaction
      without racemization. Coupling of (S)-2-N,N-di-tert-butoxycarbonyl-5
      oxopentanoate, derived from L-glutamic acid, with ortho-haloanilines provides a
      rapid access to the ring-A-substituted tryptophans in good to excellent yields.

PMID- 16995693
TI  - Syntheses and properties of water-soluble Nile Red derivatives.
AB  - Nile Red (compound A) fluoresces at about 530 nm with good quantum yields in
      apolar solvents. In more polar ones its fluorescence emission shows a dramatic,
      and potentially useful, shift to about 640 nm, but its quantum yield is
      significantly reduced. Further, Nile Red has a very poor solubility in aqueous
      media. The hypothesis tested in this paper is that Nile Red derivatives that
      incorporate water-solubilizing groups will tend to fluoresce with good quantum
      yields in aqueous media, and in the more useful wavelength range around 640 nm.
      Thus three Nile Red derivatives, 1-3, were prepared. Compound 1 had three
      hydroxyl groups more than Nile Red, but was surprisingly insoluble in aqueous
      media. However, the dicarboxylic acid 2 and carboxylic/sulfonic acid derivative 3
      showed excellent water solubilities. Spectral data for 2 and 3 showed that they
      do indeed fluoresce with good quantum yields in the 640 nm region in aqueous
      media. These properties of compounds 2 and 3 might be useful in the development
      of fluorescent probes for biotechnology.

PMID- 16995694
TI  - On the illusive nature of o-formylazobenzenes: exploiting the nucleophilicity of
      the azo group for cyclization to indazole derivatives.
AB  - Facile rearrangement of azobenzenes is shown to occur in cases where the azo
      group is placed in the ortho position to carbonyl electrophiles to furnish the
      indazole skeleton. While this study demonstrates the illusive nature of o
      formylazobenzenes, it offers potential for the synthesis of indazoles and related
      heterocycles.

PMID- 16995695
TI  - Synthesis and characterization of azobenzene-confined porphyrins.
AB  - A versatile synthetic method has been developed to incorporate photochromic
      azobenzene moieties into tetraphenylporphyrin frameworks in an orthogonal
      fashion, positioning the phenylazo substituents above and below the plane of the
      macrocycle. Surprisingly, photoisomerization is completely suppressed in the
      resulting azobenzene-confined porphyrins.

PMID- 16995696
TI  - Barbituric acid as a substituent at aryl methylium ions.
AB  - Activation of different benzophenone derivatives with triflic anhydride for
      electrophilic aromatic substitution of 5-phenylbarbituric acids leads to
      regioselective formation of the ortho-substituted product. The resulting
      triphenylmethylium salt can be isolated when the Michlers ketone is used. More
      electrophilic cations form cyclic enol ethers such as 1-n-butyl-9,9-diaryl-1,9
      dihydro-10-oxa-1,3-diazaphenanthrene-2,4-diones. Alternatively, supramolecular
      complex formation with 2,6-diacetamido pyridine as well as carbenium ion
      generation have been studied. Although in dilute acid only protonation of one of
      the carbonyl oxygens occurs, ring opening of the cyclic enol ether toward the
      carbenium ion is observed in 96% sulfuric acid.

PMID- 16995697
TI  - Recognition properties of an acyclic biphenyl-based receptor toward
      carbohydrates.
AB  - Biphenyl-based receptor 1, incorporating four heterocyclic recognition units, was
      synthesized, and its binding properties toward neutral sugars were determined.
      Receptor 1 is a representative of a new series of acyclic carbohydrate-binding
      receptors, which were designed to recognize disaccharides. The compound 1 has
      been established as a highly effective receptor for dodecyl beta-D-maltoside,
      showing successive 1:1 and 2:1 receptor/substrate complexation behavior toward
      the disaccharide. Both hydrogen bonding and interactions of the sugar CH's with
      the aromatic units of the receptor contribute to the stabilization of the
      receptor-maltoside complexes.

PMID- 16995698
TI  - Acceptor or donor (diaryl B or N) substituted octupolar truxene: synthesis,
      structure, and charge-transfer-enhanced fluorescence.
AB  - Two diaryl B- and N-substituted truxene charge-transfer compounds B3 and N3 have
      been synthesized. The fluorescence intensities of several nonfunctionalized
      truxene compounds are 1 order of magnitude weaker than that of B3 and N3. To
      reveal the structure-property correlations, the X-ray structures of B3 and N3 and
      their precursors 3 and 4 have been determined. The extended molecular dimension,
      the especially shortened B-C bond, and the improved planarity of B3 can serve as
      direct structural evidence for the charge transfer.

PMID- 16995699
TI  - Heptamethine cyanine dyes with a robust C-C bond at the central position of the
      chromophore.
AB  - Novel, highly fluorescent, monofunctional, water-soluble heptamethine cyanine
      dyes containing a robust C-C bond at the central position of the near-infrared
      fluorophore system were prepared by the Suzuki-Miyaura method. The reaction
      proceeded efficiently to replace the meso-chlorine atom with a carboxy
      functionalized aryl moiety and afforded the desired compounds in high yields.
      This methodology is particularly attractive due to its versatility and the
      utilization of environmentally friendly water as solvent. The new compounds
      possess excellent spectral properties and readily label bioactive molecules on
      solid support. The results demonstrate the potential of using the new compounds
      as fluorescent antennae for molecular imaging, spectroscopy, microscopy, and
      chemical or biological molecular recognition studies.

PMID- 16995700
TI  - Syntheses of (+)-alismoxide and (+)-4-epi-alismoxide.
AB  - The first total syntheses of (+)-alismoxide and (+)-4-epi-alismoxide are
      reported. Formal chemo-, regio-, and stereoselective addition of water to 10alpha
      acetoxy-1alphaH,5betaH-guaia-3,6-diene afforded the target compounds after
      reduction. The absolute stereochemistry of (+)-alismoxide has been established.
      The low [alpha](D) +8.6 value indicates that significant amounts of alismoxide
      result from biosynthetic processes. Furthermore, the structure of the natural
      guaienediol isolated from Silphium perfoliatum has been corrected to (-)
      alismoxide.

PMID- 16995701
TI  - Synthesis of omega-(hetero)arylalkynylated alpha-amino acid by Sonogashira-type
      reactions in aqueous media.
AB  - Mild conditions are described that allow the palladium-catalyzed cross-coupling
      of C(alpha)-alkynylated glycine with a wide variety of electron-rich and electron
      poor aryl and heteroaryl halides in aqueous media.

PMID- 16995702
TI  - Copper-catalyzed 1,2-hydroxysulfenylation of alkene using disulfide via cleavage
      of the S-S bond.
AB  - Copper-catalyzed 1,2-hydroxysulfenylation of alkenes can be carried out by the
      use of disulfides and acetic acid in air. This reaction regio- and anti
      selectively gave the corresponding 1,2-acetoxysulfides. Furthermore, the present
      method enables the use of both organosulfide groups of disulfide.

PMID- 16995703
TI  - Carbocyclic ribosylamines: synthesis of 5-substituted carbocyclic beta
      ribofuranosylamines.
AB  - A synthesis of 5-substituted cyclopentylamine precursors for 5'-substituted
      carbocyclic nucleoside analogues was developed. We show that the stereochemistry
      of the OsO4-catalyzed hydroxylation of an apically brominated lactam, 7-bromo-2
      azabicyclo[2.2.1]hept-5-en-3-one, can be controlled through the appropriate
      selection of the lactam N-H protecting group. Sterically large groups direct the
      hydroxylation to the exo-face of the olefin, yielding hydroxylation products that
      can be converted into analogues of carbocyclic ribosides. Conversely, a
      sterically small protecting group permits OsO4 approach from the endo-face,
      yielding hydroxylation products analogous to carbocyclic lyxosides. A key
      intermediate for carbocyclic sugar production, (1S,2S,3R, 4R,5S)-1-(tert
      butyloxycarbonyl)amino-5-bromo-2,3-(dimethylmethylene)dioxy-4
      hydroxymethylcyclopentane, was synthesized starting from a commercially available
      enantiomerically pure lactam, (1S)-(+)-2-azabicyclo[2.2.1]hept-5-en-3-one, in
      seven steps in an overall yield of 21%.

PMID- 16995704
TI  - Acid-catalyzed synthesis of methylene-bridged (S)-tyrosine-phenol dimers.
AB  - The efficient synthesis of 2,2'-arylmethylene dimers from 3-hydroxymethyl or 3
      methoxymethyl-5-halo-(S)-tyrosines and para-substituted phenols under acid
      catalyzed reaction conditions using either conventional or microwave-assisted
      protocols is described.

PMID- 16995705
TI  - A one-pot preparation of 1,3-disubstituted azetidines.
AB  - A straightforward synthesis of 1,3-disubstituted azetidines has been accomplished
      via the alkylation of a primary amine with the bis-triflate of a 2-substituted
      1,3-propanediol species. This transformation is carried out in one reaction
      vessel, and elimination of the alkylating reagent is generally not a major
      byproduct. The scope of this methodology has been investigated using a variety 2
      substituted-1,3-propanediols and amine nucleophiles.

PMID- 16995706
TI  - Stereoselective synthesis of (E)-mannosylidene derivatives using the Wittig
      reaction.
AB  - Stabilized ylides Bu(3)P=CH(EWG), where EWG is an ester or nitrile group, react
      with 2,3,4,6-tetra-O-benzylmannono-1,5-lactone giving high yields of
      mannosylidene derivatives; in contrast to the glucose and galactose analogues,
      the (E)-mannosylidenes are predominant (E:Z > 9:1), thus minimizing dipole-dipole
      repulsions in the Wittig reactions. NMR indicates chair-like conformations for
      solutions of the (E)-mannopyranosylidenes, but not for those (Z)-isomers where
      data are available (EWG = CN or CO(2)Et). X-ray crystallography shows an
      approximately twist-boat conformation for the tetra-O-benzyl-protected (Z)
      mannosylideneacetonitrile.

PMID- 16995707
TI  - Phosphine-catalyzed allylic substitution of Morita-Baylis-Hillman acetates:
      synthesis of N-protected beta-aminophosphonic acid esters.
AB  - A series of N-protected beta-amino phosphonic acid esters have been prepared by
      phosphine-catalyzed allylic substitution of 2-(diethylphosphonyl)-substituted
      allylic acetates employing 4,5-dichlorophthalimide as nucleophilic partner. These
      organocatalytic allylic substitutions exhibit exceptionally high levels of
      regiospecificity by virtue of a tandem S(N)2'-S(N)2' mechanism.

PMID- 16995708
TI  - A new synthesis of 2,3-dihydrobenzo[1,4]dioxine and 3,4-dihydro-2H
      benzo[1,4]oxazine derivatives by tandem palladium-catalyzed oxidative
      aminocarbonylation-cyclization of 2-prop-2-ynyloxyphenols and 2-prop-2
      ynyloxyanilines.
AB  - 2-[(Dialkylcarbamoyl)methylene]-2,3-dihydrobenzo[1,4]dioxine and 3
      [(dialkylcarbamoyl)methylene]-3,4-dihydro-2H-benzo[1,4]oxazine derivatives (3 and
      5, respectively) were synthesized for the first time starting from readily
      available 2-prop-2-ynyloxyphenols 1 and 2-prop-2-ynyloxyanilines 4, respectively,
      through tandem oxidative aminocarbonylation of the triple bond-intramolecular
      conjugate addition. Reactions were carried out in the presence of catalytic
      amounts of PdI2 in conjunction with an excess of KI in N,N-dimethylacetamide
      (DMA) as the solvent at 80-100 degrees C and under 20 atm (at 25 degrees C) of a
      4:1 mixture of CO-air. The reaction showed a significant degree of
      stereoselectivity, the Z isomers being formed preferentially or exclusively. The
      configuration around the double bond of the major stereoisomers was unequivocally
      established by X-ray diffraction analysis.

PMID- 16995709
TI  - Synthesis of C-15 vindoline analogues by palladium-catalyzed cross-coupling
      reactions.
AB  - Described are general protocols for the rapid construction of various C-15
      substituted analogues of vindoline using palladium-catalyzed cross-coupling
      reactions. The required bromo- and iodovindolines were prepared in high yield by
      the reaction of vindoline with N-bromosuccinimide or N-iodosuccinimide,
      respectively. The study not only led to the preparation of a number of
      structurally novel vindoline analogues but also opens the door to new strategies
      for the synthesis of vinblastine, vincristine, and related anticancer agents.
      Also described is the conversion of ent-tabersonine to ent-vindoline.

PMID- 16995710
TI  - Tandem addition of trialkyl phosphites to alpha,beta-unsaturated imines: a
      comparison with silylated phosphites.
AB  - Trialkyl phosphites were evaluated for addition reactions to alpha,beta
      unsaturated imines. An acidic medium is required to allow consecutive 1,4- and
      1,2-addition to occur. In this manner, 3-phosphonyl-1-aminophosphonates,
      phosphonic acid analogues of glutamate, are obtained in good yields (32-90%). The
      reaction is mainly influenced by the steric bulk of the nitrogen substituent:
      less steric N-substituents lead to better yields of the tandem adducts.

PMID- 16995711
TI  - A novel approach to oligonucleotide synthesis using an imidazolium ion tag as a
      soluble support.
AB  - The synthesis of oligonucleotides in solution using a soluble, ionic liquid based
      support is described. Short oligomers of varying base composition were
      synthesized using this method in high yields and high purity, requiring no
      chromatography for purification prior to cleavage from the support. The solution
      phase-synthesized oligomers were compared to the same sequences prepared using
      standard gene machine techniques by LCMS. This methodology may provide a cheaper
      route for the large-scale synthesis of oligonucleotides.

PMID- 16995712
TI  - Efficient total syntheses and structural verification of both diospongins A and B
      via a common delta-lactone intermediate.
AB  - The total syntheses of the two aryl C-glycoside natural products diospongins A
      and B are described. The key reactions involved stereoselective reductions of the
      appropriate oxocarbenium cations that were derived from a common delta-lactone
      intermediate.

PMID- 16995713
TI  - Synthesis of polymer-bound 4-acetoxy-3-phenylbenzaldehyde derivatives:
      applications in solid-phase organic synthesis.
AB  - Aminomethyl polystyrene resin was reacted with 4-(5'-formyl-2'
      hydroxyphenyl)benzoic acid and 4-(5'-formyl-2'-hydroxyphenyl)phenyl propionic
      acid, respectively, in the presence of 1-hydroxybenzotriazole and 1,3
      diisopropylcarbodiimide to yield polymer-bound benzaldehydes. The phenolic group
      in resins was acetylated with acetic anhydride to afford two polymer-bound 4
      acetoxybenzaldehydes. The reductive amination of polymer-bound linkers by amines
      and sodium triacetoxyborohydride, followed by sulfonylation with arylsulfonyl
      chloride derivatives in the presence of pyridine and the cleavage with
      TFA/DCM/H2O, produced pure sulfonamides.

PMID- 16995714
TI  - Efficient nitro-aldol reaction using SmI2: a new route to nitro alcohols under
      very mild conditions.
AB  - A novel method to obtain racemic 1-nitroalkan-2-ols by reaction of
      bromonitromethane with a variety of aldehydes and promoted by SmI2 is reported.
      On the basis of these results, the chiral version has also been performed with
      chiral N,N-dibenzyl amino aldehydes, affording the corresponding enantiopure 3
      amino-1-nitroalkan-2-ols with good stereoselectivity.

PMID- 16995716
TI  - Comments on "solvation parameters. 2. A simplified molecular topology to generate
      easily optimized values".
AB  - A polemic is presented in regards to a recent paper by Laffort and Hericourt [J.
      Chem. Inf. Model. 2006, 46, 1723-1734].

PMID- 16995717
TI  - Unsupervised 3D ring template searching as an ideas generator for scaffold
      hopping: use of the LAMDA, RigFit, and field-based similarity search (FBSS)
      methods.
AB  - Crystal structures taken from the Cambridge Structural Database were used to
      build a ring scaffold database containing 19 050 3D structures, with each such
      scaffold then being used to generate a centroid connecting path (CCP)
      representation. The CCP is a novel object that connects ring centroids, ring
      linker atoms, and other important points on the connection path between ring
      centroids. Unsupervised searching in the scaffold and CCP data sets was carried
      out using the atom-based LAMDA and RigFit search methods and the field-based
      similarity search method. The performance of these methods was tested with three
      different ring scaffold queries. These searches demonstrated that unsupervised 3D
      scaffold searching methods can find not only the types of ring systems that might
      be retrieved in carefully defined pharmacophore searches (supervised approach)
      but also additional, structurally diverse ring systems that could form the
      starting point for lead discovery programs or other scaffold-hopping
      applications. Not only are the methods effective but some are sufficiently rapid
      to permit scaffold searching in large chemical databases on a routine basis.

PMID- 16995718
TI  - Neural networks convergence using physicochemical data.
AB  - An investigation of the neural network convergence and prediction based on three
      optimization algorithms, namely, Levenberg-Marquardt, conjugate gradient, and
      delta rule, is described. Several simulated neural networks built using the above
      three algorithms indicated that the Levenberg-Marquardt optimizer implemented as
      a back-propagation neural network converged faster than the other two algorithms
      and provides in most of the cases better prediction. These conclusions are based
      on eight physicochemical data sets, each with a significant number of compounds
      comparable to that usually used in the QSAR/QSPR modeling. The superiority of the
      Levenberg-Marquardt algorithm is revealed in terms of functional dependence of
      the change of the neural network weights with respect to the gradient of the
      error propagation as well as distribution of the weight values. The prediction of
      the models is assessed by the error of the validation sets not used in the
      training process.

PMID- 16995719
TI  - Explicit Diversity Index (EDI): a novel measure for assessing the diversity of
      compound databases.
AB  - A novel diversity assessment method, the Explicit Diversity Index (EDI), is
      introduced for druglike molecules. EDI combines structural and synthesis-related
      dissimilarity values and expresses them as a single number. As an easily
      interpretable measure, it facilitates the decision making in the design of
      combinatorial libraries, and it might assist in the comparison of compound sets
      provided by different manufacturers. Because of its rapid calculation algorithm,
      EDI enables the diversity assessment of in-house or commercial compound
      collections.

PMID- 16995720
TI  - Characterization of DNA primary sequences by a new similarity/diversity measure
      based on the partial ordering.
AB  - The similarity/diversity measures play a fundamental role in library searching,
      virtual screening, and quantitative structure-activity relationship/quantitative
      structure-property relationship modeling as well as in genomics and proteomics.
      In this paper, a new similarity/diversity measure is proposed as a new approach
      for the analysis of sequential data, where useful information can be also
      obtained by the ordering relationships between the sequence elements. This
      methodology can be applied for evaluating molecular similarity/diversity, using
      sets of sequential descriptors, and for evaluating the similarity between
      spectra, sensor arrays, and other sequential data such as DNA and protein
      sequences. The new proposed distance (weighted standardized Hasse distance) is
      evaluated between pairs of Hasse matrices derived from the classical partial
      ordering rules. It can be naturally standardized, thus allowing the
      interpretation of these distances as absolute values (e.g., percentage) and
      deriving simple similarity and correlation indices. A simple example is taken to
      highlight the behavior of the new similarity/diversity measure on DNA sequences
      taken from the first exons of the beta-globins for eight different species.
      Sensitivity analysis has been also performed, showing the high capability of this
      measure to take into account small modifications of the DNA sequences. Finally, a
      comparison with results obtained from the literature is given, together with a
      comparison with matrix invariants derived from the Hasse matrix.

PMID- 16995721
TI  - Lingos, finite state machines, and fast similarity searching.
AB  - We apply a recently published method of text-based molecular similarity searching
      (LINGO) to standard data sets for the purpose of quantifying the accuracy of the
      approach. Our implementation is based on a pattern-matching finite state machine
      (FSM) which results in fast search times. The accuracy of LINGO is demonstrated
      to be comparable to that of a path-based fingerprint and offers a simple yet
      effective method for similarity searching.

PMID- 16995722
TI  - A fast clustering algorithm for analyzing highly similar compounds of very large
      libraries.
AB  - As a result of the recent developments of high-throughput screening in drug
      discovery, the number of available screening compounds has been growing rapidly.
      Chemical vendors provide millions of compounds; however, these compounds are
      highly redundant. Clustering analysis, a technique that groups similar compounds
      into families, can be used to analyze such redundancy. Many available clustering
      methods focus on accurate classification of compounds; they are slow and are not
      suitable for very large compound libraries. Here is described a fast clustering
      method based on an incremental clustering algorithm and the 2D fingerprints of
      compounds. This method can cluster a very large data set with millions of
      compounds in hours on a single computer. A program implemented with this method,
      called cd-hit-fp, is available from http://chemspace.org.

PMID- 16995723
TI  - QSAR--how good is it in practice? Comparison of descriptor sets on an unbiased
      cross section of corporate data sets.
AB  - The quality of QSAR (Quantitative Structure-Activity Relationships) predictions
      depends on a large number of factors including the descriptor set, the
      statistical method, and the data sets used. Here we study the quality of QSAR
      predictions mainly as a function of the data set and descriptor type using
      partial least squares as the statistical modeling method. The study makes use of
      the fact that we have access to a large number of data sets and to a variety of
      different QSAR descriptors. The main conclusions are that the quality of the
      predictions depends both on the data set and the descriptor used. The quality of
      the predictions correlates positively with the size of the data set and the range
      of biological activities. There is no clear dependence of the quality of the
      predictions on the complexity of the data set. All of the descriptors tested
      produced useful predictions for some of the data sets. None of the descriptors is
      best for all data sets; it is therefore necessary to test in each individual
      case, which descriptor produces the best model. In our tests, 2D fragment based
      descriptors usually performed better than simpler descriptors based on augmented
      atom types. Possible reasons for these observations are discussed.

PMID- 16995724
TI  - Assessment of molecular similarity from the analysis of randomly generated
      structural fragment populations.
AB  - A novel method termed MolBlaster is introduced for the evaluation of molecular
      similarity relationships on the basis of randomly generated fragment populations.
      Our motivation has been to develop a similarity method that does not depend on
      the use of predefined structural or property descriptors. Fragment profiles of
      molecules are generated by random deletion of bonds in connectivity tables and
      quantitatively compared using entropy-based metrics. In test calculations,
      MolBlaster accurately reproduced a structural key-based similarity ranking of
      druglike molecules.

PMID- 16995725
TI  - Improved naive Bayesian modeling of numerical data for absorption, distribution,
      metabolism and excretion (ADME) property prediction.
AB  - We have implemented a naive Bayesian classifier which models continuous numerical
      data using a Gaussian distribution. Several cases of interest in the area of
      absorption, distribution, metabolism, and excretion prediction are presented
      which demonstrate that this approach is superior to the implementation of naive
      Bayesian classifiers in which continuous chemical descriptors are modeled as
      binary data. We demonstrate that this enhanced performance, upon comparison with
      other implementations, is independent of the descriptor sets chosen. We also
      compare the performance of three implementations of naive Bayesian classifiers
      with other previously described models.

PMID- 16995726
TI  - Influence of alkali metal cations upon the Kolbe-Schmitt reaction mechanism.
AB  - The mechanisms of the carboxylations of lithium, potassium, rubidium, and cesium
      phenoxides are investigated by means of the DFT method with the LANL2DZ basis
      set. It is shown that the reactions of all alkali metal phenoxides with carbon
      dioxide occur via very similar reaction mechanisms. The reactions can proceed in
      the ortho and para positions. The exception is lithium phenoxide which yields
      only salicylic acid in the Kolbe-Schmitt reaction. It is found that the yield of
      the para substituted product increases with increasing the ionic radius of the
      alkali metal used. An explanation for this experimental and theoretical
      observation is proposed.

PMID- 16995727
TI  - Stability and electronic properties of nitrogen nanoneedles and nanotubes.
AB  - The electronic structures and stability of nitrogen nanostructures, nanotubes,
      and fiberlike nanoneedles of various diameters, formed by units N2m (m = 2-6),
      were studied by quantum chemistry computational modeling methods. The geometrical
      structures with various cross-sections and terminal units, their energetic
      stability, and their rather peculiar electron density distributions were
      investigated. The tightest nitrogen nanoneedle (NNN) studied theoretically in
      this work is the structure (N4n with D2h symmetry, whereas the nitrogen nanotube
      (NNT) with the largest diameter discussed here is the structure (N12)n with D2
      symmetry. These families of NNNs and NNTs can be considered as nanostructures not
      only for potential applications as devices in nanotechnology or as possible
      scaffold structures but also as ligands in synthetic chemistry and high-energy
      density materials (HEDMs). As a consequence of the lone-pair electrons present
      around the walls of these NNNs and NNTs, these nitrogen nanostructures and the
      nitrogen nano-bundles (NNB) formed by aligning and combining them using
      intermediate carbon atoms, can have highly variable electronic properties
      controlled by the changing charge environment. In particular, for extended
      systems based on the units studied here, the band gaps of each of these systems
      can be affected greatly by the local charge of the environment.

PMID- 16995728
TI  - Are automated molecular dynamics simulations and binding free energy calculations
      realistic tools in lead optimization? An evaluation of the linear interaction
      energy (LIE) method.
AB  - An extensive evaluation of the linear interaction energy (LIE) method for the
      prediction of binding affinity of docked compounds has been performed, with an
      emphasis on its applicability in lead optimization. An automated setup is
      presented, which allows for the use of the method in an industrial setting.
      Calculations are performed for four realistic examples, retinoic acid receptor
      gamma, matrix metalloprotease 3, estrogen receptor alpha, and dihydrofolate
      reductase, focusing on different aspects of the procedure. The obtained LIE
      models are evaluated in terms of the root-mean-square (RMS) errors from
      experimental binding free energies and the ability to rank compounds
      appropriately. The results are compared to the best empirical scoring function,
      selected from a set of 10 scoring functions. In all cases, good LIE models can be
      obtained in terms of free-energy RMS errors, although reasonable ranking of the
      ligands of dihydrofolate reductase proves difficult for both the LIE method and
      scoring functions. For the other proteins, the LIE model results in better
      predictions than the best performing scoring function. These results indicate
      that the LIE approach, as a tool to evaluate docking results, can be a valuable
      asset in computational lead optimization programs.

PMID- 16995729
TI  - A novel automated lazy learning QSAR (ALL-QSAR) approach: method development,
      applications, and virtual screening of chemical databases using validated ALL
      QSAR models.
AB  - A novel automated lazy learning quantitative structure-activity relationship (ALL
      QSAR) modeling approach has been developed on the basis of the lazy learning
      theory. The activity of a test compound is predicted from a locally weighted
      linear regression model using chemical descriptors and the biological activity of
      the training set compounds most chemically similar to this test compound. The
      weights with which training set compounds are included in the regression depend
      on the similarity of those compounds to a test compound. We have applied the ALL
      QSAR method to several experimental chemical data sets including 48
      anticonvulsant agents with known ED50 values, 48 dopamine D1-receptor antagonists
      with known competitive binding affinities (Ki), and a Tetrahymena pyriformis data
      set containing 250 phenolic compounds with toxicity IGC50 values. When applied to
      database screening, models developed for anticonvulsant agents identified several
      known anticonvulsant compounds that were not only absent in the training set but
      highly chemically dissimilar to the training set compounds. This initial success
      indicates that ALL-QSAR can be further exploited as a general tool for accurate
      bioactivity prediction and database screening in drug design and discovery.
      Because of its local nature, the ALL-QSAR approach appears to be especially well
      suited for the development of highly predictive models for the sparse or unevenly
      distributed data sets.

PMID- 16995730
TI  - Geometric accuracy of three-dimensional molecular overlays.
AB  - This study examines the dependence of molecular alignment accuracy on a variety
      of factors including the choice of molecular template, alignment method,
      conformational flexibility, and type of protein target. We used eight test
      systems for which X-ray data on 145 ligand-protein complexes were available. The
      use of X-ray structures allowed an unambiguous assignment of bioactive overlays
      for each compound set. The alignment accuracy depended on multiple factors and
      ranged from 6% for flexible overlays to 73% for X-ray rigid overlays, when the
      conformation of the template ligand came from X-ray structures. The dependence of
      the overlay accuracy on the choice of templates and molecules to be aligned was
      found to be the most significant factor in six and seven of the eight ligand
      protein complex data sets, respectively. While finding little preference for the
      overlay method, we observed that the introduction of molecule flexibility
      resulted in a decrease of overlay accuracy in 50% of the cases. We derived rules
      to maximize the accuracy of alignment, leading to a more than 2-fold improvement
      in accuracy (from 19% to 48%). The rules also allowed the identification of
      compounds with a low (<5%) chance to be correctly aligned. Last, the accuracy of
      the alignment derived without any utilization of X-ray conformers varied from <1%
      for the human immunodeficiency virus data set to 53% for the trypsin data set. We
      found that the accuracy was directly proportional to the product of the overlay
      accuracy from the templates in their bioactive conformations and the chance of
      obtaining the correct bioactive conformation of the templates. This study
      generates a much needed benchmark for the expectations of molecular alignment
      accuracy and shows appropriate usages and best practices to maximize hypothesis
      generation success.

PMID- 16995731
TI  - The pharmacophore kernel for virtual screening with support vector machines.
AB  - We introduce a family of positive definite kernels specifically optimized for the
      manipulation of 3D structures of molecules with kernel methods. The kernels are
      based on the comparison of the three-point pharmacophores present in the 3D
      structures of molecules, a set of molecular features known to be particularly
      relevant for virtual screening applications. We present a computationally
      demanding exact implementation of these kernels, as well as fast approximations
      related to the classical fingerprint-based approaches. Experimental results
      suggest that this new approach is competitive with state-of-the-art algorithms
      based on the 2D structure of molecules for the detection of inhibitors of several
      drug targets.

PMID- 16995732
TI  - Systematic statistical comparison of comparative molecular similarity indices
      analysis molecular fields for computer-aided lead optimization.
AB  - Comparative molecular similarity indices analysis (CoMSIA) is a 3D quantitative
      structure-activity relationship technique used to determine structural and
      electronic features influencing biological activity. This proves particularly
      useful for facilitating lead optimization projects. This study aimed to compare
      CoMSIA models produced using different subsets of the CoMSIA molecular fields
      (steric, electrostatic, hydrophobic, hydrogen-bond donor, and hydrogen-bond
      acceptor) in a systematic and statistically valid manner. A total of 23 data sets
      sourced from the literature were used to compare molecular field contribution and
      model predictivity using leave-one-out cross-validated R2 values. Predictive
      ability varied in a highly statistically significant manner depending on the set
      of CoMSIA molecular fields used. In general, the greater the number of CoMSIA
      molecular fields included in the analysis, the better the model predictivity was.
      There is great redundancy in the information contained in the different CoMSIA
      molecular fields. When all five CoMSIA molecular fields are included, the
      hydrophobic and electrostatic fields had the largest and the steric field the
      smallest contribution. Data sets were clustered into four groups on the basis of
      the utility of molecular field sets to generate predictive models.

PMID- 16995733
TI  - Refinement and use of the approximate similarity in QSAR models for
      benzodiazepine receptor ligands.
AB  - Several considerations for refining the approximate similarity measurements have
      been introduced in this paper: the use of topological invariants for the
      calculation of similarity indexes and the development of new similarity
      correction processes. The quality of the new similarity measurements obtained
      with the proposed methods has permitted the development of fast, cheap, and
      simple quantitative structure-activity relationship models for the prediction of
      biological activities of nonbenzodiazepine gamma-aminobutyric
      acid(A)/benzodiazepine receptor ligands (58 compounds). Internal and external
      validations were carried out for the approximate similarity matrices computed
      using different approaches. Satisfactory results which compare reasonably well
      with a 3D approach were obtained: Q2= 0.65 and standard error in cross validation
      SECV= 0.83 for the training stage; r = 0.79 and error in external prediction =
      0.82 for the test step. In addition, the method proposed was compared with other
      topological approaches based on constitutional similarity and on fingerprints.
      Satisfactory results were obtained.

PMID- 16995734
TI  - Predicting physical-chemical properties of compounds from molecular structures by
      recursive neural networks.
AB  - In this paper, we report on the potential of a recently developed neural network
      for structures applied to the prediction of physical chemical properties of
      compounds. The proposed recursive neural network (RecNN) model is able to
      directly take as input a structured representation of the molecule and to model a
      direct and adaptive relationship between the molecular structure and target
      property. Therefore, it combines in a learning system the flexibility and general
      advantages of a neural network model with the representational power of a
      structured domain. As a result, a completely new approach to quantitative
      structure-activity relationship/quantitative structure-property relationship
      (QSPR/QSAR) analysis is obtained. An original representation of the molecular
      structures has been developed accounting for both the occurrence of specific
      atoms/groups and the topological relationships among them. Gibbs free energy of
      solvation in water, Delta(solv)G degrees , has been chosen as a benchmark for the
      model. The different approaches proposed in the literature for the prediction of
      this property have been reconsidered from a general perspective. The advantages
      of RecNN as a suitable tool for the automatization of fundamental parts of the
      QSPR/QSAR analysis have been highlighted. The RecNN model has been applied to the
      analysis of the Delta(solv)G degrees in water of 138 monofunctional acyclic
      organic compounds and tested on an external data set of 33 compounds. As a result
      of the statistical analysis, we obtained, for the predictive accuracy estimated
      on the test set, correlation coefficient R = 0.9985, standard deviation S = 0.68
      kJ mol(-1), and mean absolute error MAE = 0.46 kJ mol(-1). The inherent ability
      of RecNN to abstract chemical knowledge through the adaptive learning process has
      been investigated by principal components analysis of the internal
      representations computed by the network. It has been found that the model
      recognizes the chemical compounds on the basis of a nontrivial combination of
      their chemical structure and target property.

PMID- 16995735
TI  - Application of QSPR to mixtures.
AB  - In this paper we report an attempt to apply the QSPR approach for the analysis of
      data for mixtures. This is an extension of the conventional QSPR approach to the
      analysis of data for single molecules. The QSPR methodology was applied to a data
      set of experimental measured density of binary liquid mixtures compiled from the
      literature. The present study is aimed to develop models to predict the "delta"
      value of a mixture i.e., deviation of the experimental mixture density (MED) from
      the ideal, mole-weighted calculated mixture density (MCD). The QSPR was
      investigated in two perspectives (QMD-I and QMD-II) with respect to the creation
      of training and test sets. The study resulted in significant ensemble neural
      network and k-nearest neighbor models having statistical parameters r2, q2(10cv)
      greater than 0.9, and pred_r2 greater than 0.75. The developed models can be used
      to predict the delta and hence the density of a new mixture. The QSPR analysis
      shows the importance of hydrogen bond, polar, shape, and thermodynamic
      descriptors in determining mixture density, thus aiding in the understanding of
      molecular interactions important in molecular packing in the mixtures.

PMID- 16995736
TI  - Do the neighboring residues in a polypeptide affect the electron distribution of
      an amino acid significantly? A quantitative study using the quantum theory of
      atoms in molecules (QTAIM).
AB  - Geometries, as well as bond and atomic properties obtained with the atoms-in
      molecules theory applied on B3LYP/6-31++G//B3LYP/6-31G charge densities, of the N
      formyl amides of the nine tripeptides obtained by combining glycine, alanine, and
      serine around a central glycine residue were analyzed to check how the properties
      of the central residue are modified by other amino acids bonded to it. All of the
      molecules were optimized from an alpha-helix conformation that was also displayed
      by the optimized structure. Significant variations of the geometry (especially
      remarkable for dihedral angles) and atomic properties of the central glycine
      residue are observed when it is attached to a serine residue whose side chain is
      involved in a hydrogen bond.

PMID- 16995737
TI  - Clever and efficient method for searching optimal geometries of lennard-jones
      clusters.
AB  - An unbiased algorithm for determining global minima of Lennard-Jones (LJ)
      clusters is proposed in the present study. In the algorithm, a global minimum is
      searched by using two operators: one modifies a cluster configuration by moving
      atoms to the most stable positions on the surface of a cluster and the other
      gives a perturbation on a cluster configuration by moving atoms near the center
      of mass of a cluster. The moved atoms are selected by employing contribution of
      the atoms to the potential energy of a cluster. It was possible to find new
      global minima for LJ506, LJ521, LJ536, LJ537, LJ538, and LJ541 together with
      putative global minima of LJ clusters of 10-561 atoms reported in the literature.
      This indicates that the present method is clever and efficient for cluster
      geometry optimization.

PMID- 16995738
TI  - Noise reduction method for molecular interaction energy: application to in silico
      drug screening and in silico target protein screening.
AB  - We developed a new method to improve the accuracy of molecular interaction data
      using a molecular interaction matrix. This method was applied to enhance the
      database enrichment of in silico drug screening and in silico target protein
      screening using a protein-compound affinity matrix calculated by a protein
      compound docking software. Our assumption was that the protein-compound binding
      free energy of a compound could be improved by a linear combination of its
      docking scores with many different proteins. We proposed two approaches to
      determine the coefficients of the linear combination. The first approach is based
      on similarity among the proteins, and the second is a machine-learning approach
      based on the known active compounds. These methods were applied to in silico
      screening of the active compounds of several target proteins and in silico target
      protein screening.

PMID- 16995739
TI  - Molecular dynamic and free energy studies of primary resistance mutations in HIV
      1 protease-ritonavir complexes.
AB  - To understand the basis of drug resistance of the HIV-1 protease, molecular
      dynamic (MD) and free energy calculations of the wild-type and three primary
      resistance mutants, V82F, I84V, and V82F/I84V, of HIV-1 protease complexed with
      ritonavir were carried out. Analysis of the MD trajectories revealed overall
      structures of the protein and the hydrogen bonding of the catalytic residues to
      ritonavir were similar in all four complexes. Substantial differences were also
      found near the catalytic binding domain, of which the double mutant complex has
      the greatest impact on conformational changes of the protein and the inhibitor.
      The tip of the HIV-1 protease flap of the double mutant has the greater degree of
      opening with respect to that of the others. Additionally, the phenyl ring of
      Phe82 moves away from the binding pocket S1', and the conformational change of
      ritonavir subsite P1' consequently affects the cavity size of the protein and the
      conformational energy of the inhibitor. Calculations of binding free energy using
      the solvent continuum model were able to reproduce the same trend of the
      experimental inhibition constant. The results show that the resistance mutants
      require hydrophobic residues to maintain the interactions in the binding pocket.
      Changes of the cavity volume correlate well with free energy penalties due to the
      mutation and are responsible for the loss of drug susceptibility.

PMID- 16995740
TI  - Comparative analysis of binding energy of chymostatin with human cathepsin A and
      its homologous proteins by molecular orbital calculation.
AB  - Cathepsin A is a mammalian lysosomal enzyme that catalyzes the hydrolysis of the
      carboxy-terminal amino acids of polypeptides and also regulates beta
      galactosidase and neuraminidase-1 activities through the formation of a
      multienzymic complex in lysosomes. Human cathepsin A (hCathA), yeast
      carboxypeptidase (CPY), and wheat carboxypeptidase II (CPW) belong to the
      alpha/beta-hydrolase fold family. They have structurally similar active-site
      clefts, but there are small differences in the amino acid residues comprising
      their active sites that might determine the substrate specificity and sensitivity
      to microbial inhibitors including chymostatin. To examine the selectivity and
      binding mechanism of chymostatin as to hCathA, CPY, and CPW at the atomic level,
      we analyzed the interaction energy between chymostatin and each protein
      quantitatively by semiempirical molecular orbital calculation AM1 with the
      continuum solvent model. We predicted the electrostatic repulsion between the P3
      cyclic arginine residue of the inhibitor and the Arg344 in the S3 active subsite
      of hCathA. Genetic conversion of Arg344 of the wild-type hCathA to Ile also
      caused an increase in its sensitivity to chymostatin, which was correlated with
      the decrease in the interaction energy calculated with the molecular orbital
      method. The present results suggest that such molecular calculation should be
      useful for evaluating the interactions between ligands, including inhibitors and
      homologous enzymes, in their docking models.

PMID- 16995741
TI  - A preliminary in silico lead series of 2-phthalimidinoglutaric acid analogues
      designed as MMP-3 inhibitors.
AB  - Matrix metalloproteinases (MMPs) have been the subject of intense research
      because of their roles in tumor metastasis and in the rise and spread of
      degenerative diseases such as osteo- and rheumatoid arthritis. A preliminary
      class of 140 druglike, small-molecule matrix metalloproteinase-3 inhibitors,
      intended as starting scaffolds for optimization and synthesis, has been designed
      in silico using a series of highly predictive three-dimensional quantitative
      structure-activity relationship models, including comparative molecular field
      analysis and comparative molecular similarity indices analysis, with docking and
      scoring. Thalidomide was chosen as the skeleton on which to base the new lead
      series, as it moderately inhibits MMP-3, is antiangiogenic, and lends itself
      easily to structural modifications. Most of the new compounds demonstrate medium
      to high predicted biological activity and good bioavailability as estimated by
      the octanol-water partition coefficient ClogP. Compound 102 in particular
      exhibits extremely favorable predicted activity against MMP-3; is moderately
      bioavailable; satisfies Lipinski's Rule of Five; and shows promise for further
      optimization, synthesis, and experimental evaluation as a potential adjunct
      anticancer or antirheumatic therapeutic.

PMID- 16995742
TI  - Introducing the consensus modeling concept in genetic algorithms: application to
      interpretable discriminant analysis.
AB  - An evolutionary statistical learning method was applied to classify drugs
      according to their biological target and also to discriminate between a
      compilation of oral and nonoral drugs. The emphasis was placed not only on how
      well the models predict but also on their interpretability. In an enhancement to
      previous studies, the consistency of the model weights over several runs of the
      genetic algorithm was considered with the goal of producing comprehensible
      models. Via this approach, the descriptors and their ranges that contribute most
      to class discrimination were identified. Selecting a bin step size that enables
      the average descriptor properties of the class being trained to be captured
      improves the interpretability and discriminatory power of a model. The
      performance, consistency, and robustness of such models were further enhanced by
      using two novel approaches that reduce the variability between individual
      solutions: consensus and splice modeling. Finally, the ability of the genetic
      algorithm to discriminate between activity classes was compared with a similarity
      searching method, while naive Bayes classifiers and support vector machines were
      applied in discriminating the oral and nonoral drugs.

PMID- 16995743
TI  - QSAR modeling of in vitro inhibition of cytochrome P450 3A4.
AB  - We report the QSAR modeling of cytochrome P450 3A4 (CYP3A4) enzyme inhibition
      using four large data sets of in vitro data. These data sets consist of marketed
      drugs and drug-like compounds all tested in four assays measuring the inhibition
      of the metabolism of four different substrates by the CYP3A4 enzyme. The four
      probe substrates are benzyloxycoumarin, testosterone, benzyloxyresorufin, and
      midazolam. We first show that using state-of-the-art QSAR modeling approaches
      applied to only one of these four data sets does not lead to predictive models
      that would be useful for in silico filtering of chemical libraries. We then
      present the development and the testing of a multiple pharmacophore hypothesis
      (MPH) that is formulated as a conceptual extension of the traditional QSAR
      approach to modeling the promiscuous binding of a large variety of drugs to
      CYP3A4. In the simplest form, the MPH approach takes advantage of the multiple
      substrate data sets and identifies the binding of test compounds as either
      proximal or distal relative to that of a given substrate. Application of the
      approach to the in silico filtering of test compounds for potential inhibitors of
      CYP3A4 is also presented. In addition to an improvement in the QSAR modeling for
      the inhibition of CYP3A4, the results from this modeling approach provide
      structural insights into the drug-enzyme interactions. The existence of multiple
      inhibition data sets in the BioPrint database motivates the original development
      of the concept of a multiple pharmacophore hypothesis and provides a unique
      opportunity for formulating alternative strategies of QSAR modeling of the
      inhibition of the in vitro metabolism of CYP3A4.

PMID- 16995744
TI  - Combining 4D pharmacophore generation and multidimensional QSAR: modeling ligand
      binding to the bradykinin B2 receptor.
AB  - We recently reported the development of two receptor-modeling concepts (software
      Quasar and Raptor) based on multidimensional quantitative structure-activity
      relationships (QSAR) and allowing for the explicit simulation of induced fit. As
      the identification of the bioactive configuration of ligand molecules in such
      studies is all but unambiguous, each compound may be represented by an ensemble
      of different conformations, orientations, stereoisomers, and protonation states,
      leading to a 4D data set. In this account, we present a novel technology
      (software Symposar) allowed to automatically generate a 4D pharmacophore as input
      for multidimensional QSAR. Symposar aligns ligands utilizing fuzzylike 2D
      subfeature mapping and, subsequently, a Monte Carlo search on a 3D similarity
      grid. The two-step concept (4D pharmacophore generation and quantification of
      ligand binding by multidimensional QSAR) was applied to 186 compounds binding to
      the bradykinin B2 receptor. The prediction of their binding affinity by means of
      the Quasar and Raptor technologies allowed for consensus scoring and generated
      topologically and quantitatively consistent receptor models. These converged at a
      cross-validated r2 of 0.752 and 0.815 and yielded a predictive r2 of 0.784 and
      0.853 for a test set (for Quasar and Raptor, respectively).

PMID- 16995745
TI  - Parallel screening: a novel concept in pharmacophore modeling and virtual
      screening.
AB  - Parallel screening comprises a novel in silico method to predict the potential
      biological activities of a compound by screening it with a multitude of
      pharmacophore models. Our aim is to provide a fast, large-scale system that
      allows for virtual activity profiling. In this proof of principle study, carried
      out with the software tools LigandScout and Catalyst, we present a model work for
      the application of parallel pharmacophore-based virtual screening on a set of 50
      structure-based pharmacophore models built for various viral targets and 100
      antiviral compounds. The latter were screened against all pharmacophore models in
      order to determine if their biological targets could be correctly predicted via
      an enrichment of corresponding pharmacophores matching these ligands. The results
      demonstrate that the desired enrichment, that is, successful virtual activity
      profiling, was achieved for approximately 90% of all input molecules. We discuss
      descriptors for output validation, as well as various aspects influencing the
      analysis of the obtained activity profiles, and the effect of the utilized search
      modus for screening.

PMID- 16995746
TI  - Elucidation of characteristic structural features of ligand binding sites of
      protein kinases: a neural network approach.
AB  - Protein kinases play important roles in regulating cellular signal transduction
      and other biochemical processes, and they are attractive targets for drug
      discovery programs in many disease areas. Most kinase inhibitors under
      development as drugs act by directly competing with ATP at the ATP-binding site
      of the kinase. There are more than 500 protein kinases, and the ATP-binding site
      is highly conserved among them. Therefore selectivity is an essential requirement
      for clinically effective drugs, and understanding the structural characteristics
      of ATP-binding sites is of crucial importance. The objective of the present study
      was to elucidate the structural characteristics of the adenosine-binding site of
      four major kinase groups, AGC (PKA, PKG, and PKC families), CaMK
      (calcium/calmodulin-dependent protein kinases), CMGC (CDK, MAPK, GSK3, and CLK
      families), and TK (tyrosine kinases). To do this, we classified the kinases into
      groups by using feed-forward multilayer perceptron (MLP) neural networks and
      structural, electronic, and hydrophobic descriptors of the amino acids at the
      adenosine-binding site. A total of 275 kinases were classified in two ways: (1)
      kinases belonging to a certain group were distinguished from those not belonging
      to that group, and (2) all of the kinases were classified into four groups. More
      than 85% of the kinases were correctly classified by both methods. Trained neural
      networks clarified which amino acids and which properties characterize the
      adenosine-binding site of each group, and the results were visualized by
      molecular graphics. Comparison of the modeled neural networks and the
      distributions of amino acids provided more detailed information on the structural
      characteristics of each group. Application of the present results to drug
      development is also discussed.

PMID- 16995747
TI  - Comparative QSAR- and fragments distribution analysis of drugs, druglikes,
      metabolic substances, and antimicrobial compounds.
AB  - A number of binary QSAR models have been developed using methods of artificial
      neural networks, k-nearest neighbors, linear discriminative analysis, and
      multiple linear regression and have been compared for their ability to recognize
      five types of chemical compounds that include conventional drugs, inactive
      druglikes, antimicrobial substituents, and bacterial and human metabolites. Thus,
      20 binary classifiers have been created using a variety of 'inductive' and
      traditional 2D QSAR descriptors which allowed up to 99% accurate separation of
      the studied groups of activities. The comparison of the performance by four
      computational approaches demonstrated that the neural nets result in generally
      more accurate predictions, followed closely by k-nearest neighbors methods. It
      has also been demonstrated that complementation of 'inductive' descriptors with
      conventional QSAR parameters does not generally improve the quality of resulting
      solutions, conforming high predictive ability of 'inductive' variables. The
      conducted comparative QSAR analysis based on a novel linear optimization approach
      has helped to identify the extent of overlapping between the studied groups of
      compounds, such as cross-recognition of bacterial metabolites and antimicrobial
      compounds reflecting their immanent resemblance and similar origin. Human
      metabolites have been characterized as a very distinctive class of substances,
      separated from all other groups in the descriptors space and exhibiting different
      QSAR behavior. The analysis of unique structural fragments and substituents
      revealed inhomogeneous scale-free organization of human metabolites illustrating
      the fact that certain molecular scaffolds (such as sugars and nucleotides) may be
      strongly favored by natural evolution. The established scale-free organization of
      human metabolites has been contemplated as a factor of their unique positioning
      in the descriptors space and their distinctive QSAR properties. It is anticipated
      that the study may bring additional insight into QSAR determinants for
      conventional drugs, inactive chemicals, and metabolic substances and may help in
      rationalizing design and discovery of novel antimicrobials and human therapeutics
      with improved, metabolite-like properties.

PMID- 16995748
TI  - Absolute net charge and the biological activity of oligopeptides.
AB  - Sequences of human proteins are frequently prepared as synthetic oligopeptides to
      assess their functional ability to act as compounds modulating pathways involving
      the parent protein. Our objective was to analyze a set of oligopeptides, to
      determine if their solubility or activity correlated with features of their
      primary sequence, or with features of properties inferred from three-dimensional
      structural models derived by conformational searches. We generated a
      conformational database for a set of 78 oligopeptides, derived from human
      proteins, and correlated their 3D structures with solubility and biological assay
      activity (as measured by platelet activation and inhibition). Parameters of these
      conformers (frequency of coil, frequency of turns, the degree of packing, and the
      energy) did not correlate with solubility, which was instead partly predicted by
      two measures obtained from primary sequence analysis, that is, the hydrophobic
      moment and the number of charges. The platelet activity of peptides was
      correlated with a parameter derived from the structural modeling; this was the
      second virial coefficient (a measure of the tendency for a structure to
      autoaggregate). This could be explained by an excess among the active peptides of
      those which had either a large number of positive charges or in some cases a
      large number of negative charges, with a corresponding deficit of peptides with a
      mixture of negative and positive charges. We subsequently determined that a panel
      of 523 commercially available (and biologically active) peptides shared this
      elevation of absolute net charge: there were significantly lower frequencies of
      peptides of mixed charges compared to expectations. We conclude that the design
      of biologically active peptides should consider favoring those with a higher
      absolute net charge.

PMID- 16995749
TI  - Sensitivity of vertebral compressive strength to endplate loading distribution.
AB  - The sensitivity of vertebral body strength to the distribution of axial forces
      along the endplate has not been comprehensively evaluated. Using quantitative
      computed tomography-based finite element models of 13 vertebral bodies, an
      optimization analysis was performed to determine the endplate force distributions
      that minimized (lower bound) and maximized (upper bound) vertebral strength for a
      given set of externally applied axial compressive loads. Vertebral strength was
      also evaluated for three generic boundary conditions: uniform displacement,
      uniform force, and a nonuniform force distribution in which the interior of the
      endplate was loaded with a force that was 1.5 times greater than the periphery.
      Our results showed that the relative difference between the upper and lower
      bounds on vertebral strength was 14.2 +/- 7.0% (mean +/- SD). While there was a
      weak trend for the magnitude of the strength bounds to be inversely proportional
      to bone mineral density (R2 = 0.32, p = 0.02), both upper and lower bound
      vertebral strength measures were well predicted by the strength response under
      uniform displacement loading conditions (R2 = 0.91 and R2 = 0.99, respectively).
      All three generic boundary conditions resulted in vertebral strength values that
      were statistically indistinguishable from the loading condition that resulted in
      an upper bound on strength. The results of this study indicate that the
      uncertainty in strength arising from the unknown condition of the disc is
      dependent on the condition of the bone (whether it is osteoporotic or normal).
      Although bone mineral density is not a good predictor of strength sensitivity,
      vertebral strength under generic boundary conditions, i.e., uniform displacement
      or force, was strongly correlated with the relative magnitude of the strength
      bounds. Thus, explicit disc modeling may not be necessary.

PMID- 16995750
TI  - Simulation of impact test for determining "health" of percutaneous bone anchored
      implants.
AB  - There is an ongoing requirement for a clinically relevant, noninvasive technique
      to monitor the integrity of percutaneous implants used for dental restorations,
      bone-anchored hearing aids, and to retain extra-oral prostheses (ear, eye, nose,
      etc). Because of the limitations of conventional diagnostic techniques (CT, MRI),
      mechanical techniques that measure the dynamic response of the implant-abutment
      system are being developed. This paper documents a finite element analysis that
      simulates a transient response to mechanical impact testing using contact
      elements. The detailed model allows for a specific interface between the implant
      and bone and characterizes potential clinical situations including loss of bone
      margin height, loss of osseointegration, and development of a soft connective
      tissue layer at the bone-implant interface. The results also show that the
      expected difference in interface stiffness between soft connective tissue and
      osseointegrated bone will cause easily measurable changes in the response of the
      implant/abutment system. With respect to the loss of bone margin height, changes
      in the order of 0.2 mm should be detectable, suggesting that this technique is at
      least as sensitive as radiography. A partial loss of osseointegration, while not
      being as readily evident as a bone margin loss, would still be detectable for
      losses as small as 0.5 mm.

PMID- 16995751
TI  - Comparison of plate-screw systems used in mandibular fracture reduction: finite
      element analysis.
AB  - A finite element model of the human dentate mandible has been developed to
      provide a comparison of fixation systems used currently for fracture reduction.
      Volume domains for cortical bone, cancellous bone, and teeth were created and
      meshed in ANSYS 8.0 based on IGES curves created from computerized tomography
      data. A unilateral molar clench was loaded on the model with a fracture gap
      simulated along the symphysis. Results based on Von Mises stress in cortical and
      cancellous bone surrounding the screws, and on fracture surface spatial fixation,
      show some relative differences between different screw-plate systems, yet all
      were judged to be appropriate in their reduction potential.

PMID- 16995752
TI  - Anterior displacement of the TMJ disk: repositioning of the disk using a Mitek
      system. A 3D finite element study.
AB  - In this paper the behaviors of the temporomandibular joint (TMJ) with an
      anteriorly displaced disk without reduction and with a surgically repositioned
      one were compared with the response of a healthy disk during jaw opening. The
      movement of each joint was obtained imposing the same opening path between
      incisors and assuming that the movement of the condyle is determined by the
      passive action of the masticatory muscles and the restrictions imposed by the
      articulating surfaces and the ligaments. A fiber-reinforced porohyperelastic
      model was used to simulate the behavior of the articular disk. The influence of
      the friction coefficient in the diseased joint was also analyzed, finding that
      the final displacement of the complex condyle-disk was smaller as the friction
      coefficient increased. On the other hand, its displacement in the repositioned
      joint was different than in the healthy case because the artificial sutures used
      in the surgery do not fully stabilize the disk posteriorly as the retrodiscal
      tissue does. The stress response of the disk changed in both pathologic cases: in
      the displaced joint the highest stresses moved from the intermediate zone
      (healthy case) to the posterior band, and in the reconstructed one the most
      loaded zone moved posteriorly at total opening. Besides, local stress
      concentrations appeared in the neighborhood of the artificial sutures and
      therefore damage of the disk and releasing of the sutures might be possible
      postoperatively.

PMID- 16995753
TI  - Mitochondrial dynamics in chondrocytes and their connection to the mechanical
      properties of the cytoplasm.
AB  - BACKGROUND: The motion and redistribution of intracellular organelles is a
      fundamental process in cells. Organelle motion is a complex phenomenon that
      depends on a large number of variables including the shape of the organelle, the
      type of motors with which the organelles are associated, and the mechanical
      properties of the cytoplasm. This paper presents a study that characterizes the
      diffusive motion of mitochondria in chondrocytes seeded in agarose constructs and
      what this implies about the mechanical properties of the cytoplasm. METHOD OF
      APPROACH: Images showing mitochondrial motion in individual cells at 30 s
      intervals for 15 min were captured with a confocal microscope. Digital image
      correlation was used to quantify the motion of the mitochondria, and the mean
      square displacement (MSD) was calculated. Statistical tools for testing whether
      the characteristic motion of mitochondria varied throughout the cell were
      developed. Calculations based on statistical mechanics were used to establish
      connections between the measured MSDs and the mechanical nature of the cytoplasm.
      RESULTS: The average MSD of the mitochondria varied with time according to a
      power law with the power term greater than 1, indicating that mitochondrial
      motion can be viewed as a combination of diffusion and directional motion.
      Statistical analysis revealed that the motion of the mitochondria was not uniform
      throughout the cell, and that the diffusion coefficient may vary by over 50%,
      indicating intracellular heterogeneity. High correlations were found between
      movements of mitochondria when they were less than 2 microm apart. The
      correlation is probably due to viscoelastic properties of the cytoplasm.
      Theoretical analysis based on statistical mechanics suggests that directed
      diffusion can only occur in a material that behaves like a fluid on large time
      scales. CONCLUSIONS: The study shows that mitochondria in different regions of
      the cell experience different characteristic motions. This suggests that the
      cytoplasm is a heterogeneous viscoelastic material. The study provides new
      insight into the motion of mitochondria in chondrocytes and its connection with
      the mechanical properties of the cytoplasm.

PMID- 16995754
TI  - Numerical simulation of noninvasive blood pressure measurement.
AB  - In this paper, a simulation model based on the partially pressurized collapsible
      tube model for reproducing noninvasive blood pressure measurement is presented.
      The model consists of a collapsible tube, which models the pressurized part of
      the artery, rigid pipes connected to the collapsible tube, which model proximal
      and distal region far from the pressurized part, and the Windkessel model, which
      represents the capacitance and the resistance of the distal part of the
      circulation. The blood flow is simplified to a one-dimensional system. Collapse
      and expansion of the tube is represented by the change in the cross-sectional
      area of the tube considering the force balance acting on the tube membrane in the
      direction normal to the tube axis. They are solved using the Runge-Kutta method.
      This simple model can easily reproduce the oscillation of inner fluid and
      corresponding tube collapse typical for the Korotkoff sounds generated by the
      cuff pressure. The numerical result is compared with the experiment and shows
      good agreement.

PMID- 16995755
TI  - Asymptotically consistent numerical approximation of hemolysis.
AB  - In a previous communication, we have proposed a numerical framework for the
      prediction of in vitro hemolysis indices in the preselection and optimization of
      medical devices. This numerical methodology is based on a novel interpretation of
      Giersiepen-Wurzinger blood damage correlation as a volume integration of a damage
      function over the computational domain. We now propose an improvement of this
      approach based on a hyperbolic equation of blood damage that is asymptotically
      consistent. Consequently, while the proposed correction has yet to be proven
      experimentally, it has the potential to numerically predict more realistic red
      blood cell destruction in the case of in vitro experiments. We also investigate
      the appropriate computation of the shear stress scalar of the damage fraction
      model. Finally, we assess the validity of this consistent approach with an
      analytical example and with some 3D examples.

PMID- 16995756
TI  - Laminar airflow and nanoparticle or vapor deposition in a human nasal cavity
      model.
AB  - The transport and deposition of nanoparticles, i.e., dp = 1-2 nm, or equivalent
      vapors, in the human nasal cavities is of interest to engineers, scientists, air
      pollution regulators, and healthcare officials alike. Tiny ultrafine particles,
      i.e., dp < or = 5 nm, are of special interest because they are most rapidly
      absorbed and hence have an elevated toxic or therapeutic impact when compared to
      larger particles. Assuming transient laminar 3-D incompressible flow in a
      representative human nasal cavity, the cyclic airflow pattern as well as local
      and overall nanoparticle depositions were computationally simulated and analyzed.
      The focus was on transient effects during inhalation/exhalation as compared to
      the steady-state assumption typically invoked. Then, an equation for a matching
      steady-state inhalation flow rate was developed that generates the same
      deposition results as cyclic inhalation. Of special interest is the olfactory
      region where the narrow channel surfaces receive only about one-half of a percent
      of the inhaled nanoparticles because the airflow bypasses these recesses located
      in the superior-most portions in the geometrically complex nasal cavities.

PMID- 16995757
TI  - Effects of inertia and gravity on liquid plug splitting at a bifurcation.
AB  - Liquid plugs may form in pulmonary airways during the process of liquid
      instillation or removal in many clinical treatments. During inspiration the plug
      may split at airway bifurcations and lead to a nonuniform final liquid
      distribution, which can adversely affect treatment outcomes. In this paper, a
      combination of bench top experimental and theoretical studies is presented to
      study the effects of inertia and gravity on plug splitting in an airway
      bifurcation model to simulate the liquid distributions in large airways. The
      splitting ratio, Rs, is defined as the ratio of the plug volume entering the
      upper (gravitationally opposed) daughter tube to the lower (gravitationally
      favored) one. Rs is measured as a function of parent tube Reynolds number, Rep;
      gravitational orientations for roll angle, phi, and pitch angle, gamma; parent
      plug length LP; and the presence of pre-existing plug blockages in downstream
      daughter tubes. Results show that increasing Rep causes more homogeneous
      splitting. A critical Reynolds number Rec is found to exist so that when Rep < or
      = Rec, Rs = 0, i.e., no liquid enters the upper daughter tube. Rec increases
      while Rs decreases with increasing the gravitational effect, i.e., increasing phi
      and gamma. When a blockage exists in the lower daughter, Rec is only found at phi
      = 60 deg in the range of Rep studied, and the resulting total mass ratio can be
      as high as 6, which also asymptotes to a finite value for different phi as Rep
      increases. Inertia is further demonstrated to cause more homogeneous plug
      splitting from a comparison study of Rs versus Cap (another characteristic speed)
      for three liquids: water, glycerin, and LB-400X. A theoretical model based on
      entrance flow for the plug in the daughters is developed and predicts Rs versus
      Rep. The frictional pressure drop, as a part of the total pressure drop, is
      estimated by two fitting parameters and shows a linear relationship with Rep. The
      theory provides a good prediction on liquid plug splitting and well simulates the
      liquid distributions in the large airways of human lungs.

PMID- 16995758
TI  - Dynamic simulation pericardial bioprosthetic heart valve function.
AB  - While providing nearly trouble-free function for 10-12 years, current
      bioprosthetic heart valves (BHV) continue to suffer from limited long-term
      durability. This is usually a result of leaflet calcification and/or structural
      degeneration, which may be related to regions of stress concentration associated
      with complex leaflet deformations. In the current work, a dynamic three
      dimensional finite element analysis of a pericardial BHV was performed with a
      recently developed FE implementation of the generalized nonlinear anisotropic
      Fung-type elastic constitutive model for pericardial BHV tissues (W. Sun and M.S.
      Sacks, 2005, [Biomech. Model. Mechanobiol., 4(2-3), pp. 190-199]). The
      pericardial BHV was subjected to time-varying physiological pressure loading to
      compute the deformation and stress distribution during the opening phase of the
      valve function. A dynamic sequence of the displacements revealed that the free
      edge of the leaflet reached the fully open position earlier and the belly region
      followed. Asymmetry was observed in the resulting displacement and stress
      distribution due to the fiber direction and the anisotropic characteristics of
      the Fung-type elastic constitutive material model. The computed stress
      distribution indicated relatively high magnitudes near the free edge of the
      leaflet with local bending deformation and subsequently at the leaflet attachment
      boundary. The maximum computed von Mises stress during the opening phase was 33.8
      kPa. The dynamic analysis indicated that the free edge regions of the leaflets
      were subjected to significant flexural deformation that may potentially lead to
      structural degeneration after millions of cycles of valve function. The regions
      subjected to time varying flexural deformation and high stresses of the present
      study also correspond to regions of tissue valve calcification and structural
      failure reported from explanted valves. In addition, the present simulation also
      demonstrated the importance of including the bending component together with the
      in-plane material behavior of the leaflets towards physiologically realistic
      deformation of the leaflets. Dynamic simulations with experimentally determined
      leaflet material specification can be potentially used to modify the valve
      towards an optimal design to minimize regions of stress concentration and
      structural failure.

PMID- 16995759
TI  - A model of stress and strain in the interosseous ligament of the forearm based on
      fiber network theory.
AB  - Fiber network theory was developed to describe cloth, a thin material with
      strength in the fiber directions. The interosseous ligament (IOL) of the forearm
      is a broad, thin ligament with highly aligned fibers. The objectives of this
      study were to develop a model of the stress and strain distributions in the IOL,
      based on fiber network theory, to compare the strains from the model with the
      experimentally measured strains, and to evaluate the force distribution across
      the ligament fibers from the model. The geometries of the radius, ulna, and IOL
      were reconstructed from CT scans. Position and orientation of IOL insertion sites
      and force in the IOL were measured during a forearm compression experiment in
      pronation, neutral rotation, and supination. An optical image-based technique was
      used to directly measure strain in two regions of the IOL in neutral rotation.
      For the network model, the IOL was represented as a parametric ruled three
      dimensional surface, with rulings along local fiber directions. Fiber strains
      were calculated from the deformation field, and fiber stresses were calculated
      from the strains using average IOL tensile properties from a previous study. The
      in situ strain in the IOL was assumed uniform and was calculated so that the net
      force predicted by the network model in neutral rotation matched the experimental
      result. The net force in the IOL was comparable to experimental results in
      supination and pronation. The model predicted higher stress and strain in fibers
      near the elbow in neutral rotation, and higher stresses in fibers near the wrist
      in supination. Strains in neutral forearm rotation followed the same trends as
      those measured experimentally. In this study, a model of stress and strain in the
      IOL utilizing fiber network theory was successfully implemented. The model
      illustrates variations in the stress and strain distribution in the IOL. This
      model can be used to show surgeons how different fibers are taut in different
      forearm rotation positions-this information is important for understanding the
      biomechanical role of the IOL and for planning an IOL reconstruction.

PMID- 16995760
TI  - Water movement in tendon in response to a repeated static tensile load using one
      dimensional magnetic resonance imaging.
AB  - Rabbit Achilles tendons (N = 8) were subjected to tensile loading while internal
      water movements were followed using NMR. The distribution of the internal water
      in tendons was measured using a one-dimensional proton-density map that was
      collected along a radial line oriented transverse to the tendon's long axis. The
      proton density map was created from fits to T2 relaxation data. The experimental
      design included two cycles of loading (7.5 N tensile load) and relaxation. The
      first load application was for 42.67 min: unloaded for 21.33 min, reloaded for
      21.33 min, and then unloaded for 21.33 min. Water was redistributed in a time
      dependent fashion upon loading: proton density decreased in the core region and
      increased in the rim region. In addition there was evidence that tensile loading
      caused water to become NMR visible. In separate, parallel experiments, we studied
      the mechanical behavior of tendons using identical conditions of uniaxial loading
      (N = 7). The time constants of water movements were very different from the time
      constants of mechanical relaxation, indicating that water redistribution is not
      the sole determining factor of mechanical behavior.

PMID- 16995761
TI  - Myocardial material parameter estimation-a comparative study for simple shear.
AB  - The study of ventricular mechanics-analyzing the distribution of strain and
      stress in myocardium throughout the cardiac cycle-is crucially dependent on the
      accuracy of the constitutive law chosen to represent the highly nonlinear and
      anisotropic properties of passive cardiac muscle. A number of such laws have been
      proposed and fitted to experimental measurements of stress-strain behavior. Here
      we examine five of these laws and compare them on the basis of (i) "goodness of
      fit:" How well they fit a set of six shear deformation tests, (ii)
      "determinability:" How well determined the objective function is at the optimal
      parameter fit, and (iii) "variability:" How well determined the material
      parameters are over the range of experiments. These criteria are utilized to
      discuss the advantages and disadvantages of the constitutive laws.

PMID- 16995762
TI  - Comparison of element technologies for modeling stent expansion.
AB  - Numerical analysis has become a standard, and in fact required, component of the
      process in which new biomedical stent devices are designed and approved. Despite
      this, very little work has been performed comparing the efficiency of various
      numerical techniques currently available to the analyst. The present paper begins
      this study by comparing the computational efficiency and results achieved using
      various element technologies in the context of stent deployment simulations. The
      findings indicate that the methodologies most commonly adopted in the present
      literature/industrial practice are in many cases less than optimal with regard to
      computational efficiency.

PMID- 16995763
TI  - Effects of stent design parameters on normal artery wall mechanics.
AB  - A stent is a device designed to restore flow through constricted arteries. These
      tubular scaffold devices are delivered to the afflicted region and deployed using
      minimally invasive techniques. Stents must have sufficient radial strength to
      prop the diseased artery open. The presence of a stent can subject the artery to
      abnormally high stresses that can trigger adverse biologic responses culminating
      in restenosis. The primary aim of this investigation was to investigate the
      effects of varying stent "design parameters" on the stress field induced in the
      normal artery wall and the radial displacement achieved by the stent. The generic
      stent models were designed to represent a sample of the attributes incorporated
      in present commercially available stents. Each stent was deployed in a
      homogeneous, nonlinear hyperelastic artery model and evaluated using commercially
      available finite element analysis software. Of the designs investigated herein,
      those employing large axial strut spacing, blunted corners, and higher amplitudes
      in the ring segments induced high circumferential stresses over smaller areas of
      the artery's inner surface than all other configurations. Axial strut spacing was
      the dominant parameter in this study, i.e., all designs employing a small stent
      strut spacing induced higher stresses over larger areas than designs employing
      the large strut spacing. Increasing either radius of curvature or strut amplitude
      generally resulted in smaller areas exposed to high stresses. At larger strut
      spacing, sensitivity to radius of curvature was increased in comparison to the
      small strut spacing. With the larger strut spacing designs, the effects of
      varying amplitude could be offset by varying the radius of curvature and vice
      versa. The range of minimum radial displacements from the unstented diastolic
      radius observed among all designs was less than 90 microm. Evidence presented
      herein suggests that stent designs incorporating large axial strut spacing,
      blunted corners at bends, and higher amplitudes exposed smaller regions of the
      artery to high stresses, while maintaining a radial displacement that should be
      sufficient to restore adequate flow.

PMID- 16995764
TI  - Compressive properties of mouse articular cartilage determined in a novel micro
      indentation test method and biphasic finite element model.
AB  - The mechanical properties of articular cartilage serve as important measures of
      tissue function or degeneration, and are known to change significantly with
      osteoarthritis. Interest in small animal and mouse models of osteoarthritis has
      increased as studies reveal the importance of genetic background in determining
      predisposition to osteoarthritis. While indentation testing provides a method of
      determining cartilage mechanical properties in situ, it has been of limited value
      in studying mouse joints due to the relatively small size of the joint and
      thickness of the cartilage layer. In this study, we developed a micro-indentation
      testing system to determine the compressive and biphasic mechanical properties of
      cartilage in the small joints of the mouse. A nonlinear optimization program
      employing a genetic algorithm for parameter estimation, combined with a biphasic
      finite element model of the micro-indentation test, was developed to obtain the
      biphasic, compressive material properties of articular cartilage. The creep
      response and material properties of lateral tibial plateau cartilage were
      obtained for wild-type mouse knee joints, by the micro-indentation testing and
      optimization algorithm. The newly developed genetic algorithm was found to be
      efficient and accurate when used with the finite element simulations for
      nonlinear optimization to the experimental creep data. The biphasic mechanical
      properties of mouse cartilage in compression (average values: Young's modulus,
      2.0 MPa; Poisson's ratio, 0.20; and hydraulic permeability, 1.1 x 10(-16) m4/N-s)
      were found to be of similar orders of magnitude as previous findings for other
      animal cartilages, including human, bovine, rat, and rabbit and demonstrate the
      utility of the new test methods. This study provides the first available data for
      biphasic compressive properties in mouse cartilage and suggests a promising
      method for detecting altered cartilage mechanics in small animal models of
      osteoarthritis.

PMID- 16995765
TI  - Effect of assumed stiffness and mass density on the impact response of the human
      chest using a three-dimensional FE model of the human body.
AB  - The mass density, Young's modulus (E), tangent modulus (Et), and yield stress
      (sigma y) of the human ribs, sternum, internal organs, and muscles play important
      roles when determining impact responses of the chest associated with pendulum
      impact. A series of parametric studies was conducted using a commercially
      available three-dimensional finite element (FE) model, Total HUman Model for
      Safety (THUMS) of the whole human body, to determine the effect of changing these
      material properties on the predicted impact force, chest deflection, and the
      number of rib fractures and fractured ribs. Results from this parametric study
      indicate that the initial chest apparent stiffness was mainly influenced by the
      stiffness and mass density of the superficial muscles covering the torso. The
      number of rib fractures and fractured ribs was primarily determined by the
      stiffness of the ribcage. Similarly, the stiffness of the ribcage and internal
      organs contributed to the maximum chest deflection in frontal impact, while the
      maximum chest deflection for lateral impact was mainly affected by the stiffness
      of the ribcage. Additionally, the total mass of the whole chest had a moderately
      effect on the number of rib fractures.

PMID- 16995766
TI  - A novel single-photon counting technique applied to highly sensitive measurement
      of [Ca2+]i transient in human aortic smooth muscle cells.
AB  - This study demonstrates that aequorin, a luminescent natural dye, is useful for
      vascular cell intracellular Ca2+ concentration ([Ca2+]i) determination. A new
      single-photon counting technique was developed to resolve the effects of fluid
      flow shear stress on [Ca2+]i in human aortic smooth muscle cells (HASMCs).
      Confluent HASMCs were grown on petri dishes loaded with aequorin. Then the dishes
      were placed in a luminometer chamber after the physiological level of shear
      stress was applied to the HASMC surfaces. The chamber was housed inside a highly
      sensitive photomultiplier tube. It detected ultraweak photon emission in response
      to the [Ca2+]i transient. In the presence of 2.0 mM extracellular Ca2+, a shear
      stress of 12 dyn cm2, applied for 60 s to the top surface of the HASMC monolayer,
      elicited a sharp increase in [Ca2+]i.

PMID- 16995767
TI  - Stress relaxation of porcine gluteus muscle subjected to sudden transverse
      deformation as related to pressure sore modeling.
AB  - Computational studies of deep pressure sores (DPS) in skeletal muscles require
      information on viscoelastic constitutive behavior of muscles, particularly when
      muscles are loaded transversally as during bone-muscle interaction in sitting and
      lying immobilized patients. In this study, we measured transient shear moduli
      G(t) of fresh porcine muscles in vitro using the indentation method. We employed
      a custom-made pneumatic device that allowed rapid (2000 mms) 4 mm indentations.
      We tested 8 gluteus muscles, harvested from 5 adult pigs. Each muscle was
      indented transversally (perpendicularly to the direction of fibers) at 3
      different sites, 7 times per site, to obtain nonpreconditioned (NPC) and
      preconditioned (PC) G(t) data. Short-term (GS) and long-term (GL) shear moduli
      were obtained directly from experiments. We further fitted measured G(t) data to
      a biexponential equation G(t) = G1 x exp(-t/tau1)+ G2 x exp(-t/tau2) + Ginfinity,
      which provided good fit, visually and in terms of the correlation coefficients.
      Typically, plateau of the stress relaxation curves (defined as 10% difference
      from final GL) was evident approximately 20 s after indentation. Short-term shear
      moduli GS (mean NPC: 8509 Pa, PC: 5711 Pa) were greater than long-term moduli GL
      (NPC: 609 Pa, PC: 807 Pa) by about an order of magnitude. Statistical analysis of
      parameters showed that only G2 was affected by preconditioning, while GL, GS,
      Ginfinity, tau1, tau2, and G1 properties were unaffected. Since DPS develop over
      time scales of minutes to hours, but most stress relaxation occurs within
      approximately 20 s, the most relevant property for computational modeling is GL
      (mean approximately 700 Pa), which is, conveniently, unaffected by
      preconditioning.

PMID- 16995768
TI  - An efficient robotic tendon for gait assistance.
AB  - A robotic tendon is a spring based, linear actuator in which the stiffness of the
      spring is crucial for its successful use in a lightweight, energy efficient,
      powered ankle orthosis. Like its human analog, the robotic tendon uses its
      inherent elastic nature to reduce both peak power and energy requirements for its
      motor. In the ideal example, peak power required of the motor for ankle gait is
      reduced from 250 W to just 77 W. In addition, ideal energy requirements are
      reduced from nearly 36 J to just 21 J. Using this approach, an initial prototype
      has provided 100% of the power and energy necessary for ankle gait in a compact
      0.95 kg package, seven times less than an equivalent motor/gearbox system.

PMID- 16995769
TI  - Controlled self-assembly of collagen fibrils by an automated dialysis system.
AB  - In vitro self-assembled collagen fibrils form a variety of different structures
      during dialysis. The self-assembly is dependent on several parameters, such as
      concentrations of collagen and alpha1-acid glycoprotein, temperature, dialysis
      time, and the acid concentration. For a detailed understanding of the assembly
      pathway and structural features like banding pattern or mechanical properties it
      is necessary to study single collagen fibrils. In this work we present a fully
      automated system to control the permeation of molecules through a membrane like a
      dialysis tubing. This allows us to ramp arbitrary diffusion rate profiles during
      the self-assembly process of macromolecules, such as collagen. The system
      combines a molecular sieving method with a computer assisted control system for
      measuring process variables. With the regulation of the diffusion rate it is
      possible to control and manipulate the collagen self-assembly process during the
      whole process time. Its performance is demonstrated by the preparation of various
      collagen type I fibrils and native collagen type II fibrils. The combination with
      the atomic force microscope (AFM) allows a high resolution characterization of
      the self-assembled fibrils. In principle, the represented system can be also
      applied for the production of other biomolecules, where a dialysis enhanced self
      assembly process is used.

PMID- 16995770
TI  - Modified Bilston nonlinear viscoelastic model for finite element head injury
      studies.
AB  - This paper proposes a modified nonlinear viscoelastic Bilston model (Bilston et
      al., 2001, Biorheol., 38, pp. 335-345). for the modeling of brain tissue
      constitutive properties. The modified model can be readily implemented in a
      commercial explicit finite element (FE) code, PamCrash. Critical parameters of
      the model have been determined through a series of rheological tests on porcine
      brain tissue samples and the time-temperature superposition (TTS) principle has
      been used to extend the frequency to a high region. Simulations by using PamCrash
      are compared with the test results. Through the use of the TTS principle, the
      mechanical and rheological behavior at high frequencies up to 10(4) rads may be
      obtained. This is important because the properties of the brain tissue at high
      frequencies and impact rates are especially relevant to studies of traumatic head
      injury. The averaged dynamic modulus ranges from 130 Pa to 1500 Pa and loss
      modulus ranges from 35 Pa to 800 Pa in the frequency regime studied (0.01 rads to
      3700 rads). The errors between theoretical predictions and averaged relaxation
      test results are within 20% for strains up to 20%. The FEM simulation results are
      in good agreement with experimental results. The proposed model will be
      especially useful for application to FE analysis of the head under impact loads.
      More realistic analysis of head injury can be carried out by incorporating the
      nonlinear viscoelastic constitutive law for brain tissue into a commercial FE
      code.

PMID- 16995772
TI  - Patch-clamp recording of human retinal photoreceptors and bipolar cells.
AB  - Photoreceptors and retinal bipolar cells are considered as nonspiking neurons;
      however, we recently showed that human rod photoreceptors can generate sodium
      action potentials in response to membrane depolarization from membrane potentials
      of -60 or -70 mV (Kawai et al., Neuron 30 [2001] 451). We performed patch-clamp
      recording of human cone photoreceptors and retinal bipolar cells to examine
      whether functional voltage-gated sodium channels are expressed in these cells as
      well as rod photoreceptors. Under current-clamp conditions, the injection of
      depolarizing current steps into a cone photoreceptor-induced marked action
      potentials. These action potentials were blocked by 1 microM tetrodotoxin, a
      voltage-gated sodium channel blocker. Under voltage-clamp conditions,
      depolarizing voltage steps-induced a fast transient inward current in several
      bipolar cells (n = 4/78). This current was activated from -70 to + 20 mV (maximal
      at -10 mV) and inactivated within 5 ms. The 10-90% rise time of this current was
      shorter than another inward current (less than one-hundredth). These results
      indicate that human cones and bipolar cells express voltage-gated sodium channels
      as rod photoreceptors. Sodium channels may serve to amplify the release of a
      neurotransmitter and to accelerate the light-dark change in photosignals.

PMID- 16995774
TI  - Effect of stratified culture compared to confluent culture in monolayer on
      proliferation and differentiation of human articular chondrocytes.
AB  - With conventional tissue culture of cells, it is generally assumed that when the
      available 2D substrate is fully occupied, growth ceases or is greatly
      reduced.However, in nature wound repair mostly involves proliferation of cells
      that are attracted to the defect site in a 3D environment.Hence, proliferation
      continues in 3D until the defect site is filled with cells contributing to repair
      tissue. With this in mind,we examined the growth behavior of human articular
      chondrocytes during stratified culture as opposed to routine culture to
      confluency. Additionally, we studied the influence of growth factors on
      proliferation during stratified culture and differentiation thereafter.
      Chondrocytes were cultured in monolayer on tissue culture plastic to confluency
      or stratified for an additional 7 days. Culture medium was based on DMEM with 10%
      serum and either supplemented with high concentrations of nonessential amino
      acids (NEAA) and ascorbic acid (AsAP), or instead with basic fibroblastic growth
      factor (bFGF), platelet-derived growth factor (PDBF-BB), and/or transforming
      growth factor beta1 (TGF-beta). After expansion, cells were harvested, counted,
      and their differentiation capacity was examined in pellet culture assay. It was
      shown that chondrocytes, cultured stratified proliferate exponentially for up to
      an additional 4 days and that cell yield increased 5-fold. Furthermore, during
      stratified culture the number of cells increased further in the presence of bFGF,
      PDBF-BB, and TGFbeta1 or high concentrations of NEAA and AsAP. Depending on donor
      variation and factors supplemented the cell yield ranged from 0.06 up to 1.1
      million cells/cm2 at the second passage. During stratified culture in the
      presence of either bFGF and PDGF or high concentrations of NEAA and AsAP,
      exponential growth continued for up to 7 days. Finally, cells maintained their
      differentiation capacity when cultured stratified with or without growth factors
      (bFGF, TGF-beta, and PDGF), but not when cultured with high levels of AsAP and
      NEAA. In contrast to other 3D culture techniques like microcarrier or suspension
      culture, nutrient consumption remained the same as with conventional expansion.
      Because this allows culturing of clinically relevant amounts of chondrocytes
      without increasing the amount of serum, chondrocytes can be fully expanded in the
      presence autologous serum, avoiding the risk of viral and/or prion disease
      transmission associated with the use of animal-derived serum or serum replacers
      with animal-derived constituents.

PMID- 16995775
TI  - Update on tissue-engineered biological dressings.
AB  - Tissue-engineered biological dressings offer promise in the treatment of burns,
      chronic ulcers, donor site and other surgical wounds, and a variety of blistering
      and desquamating dermatologic conditions. For example, the prevalence of diabetic
      foot ulcers ranges from 4.4% to 10.5% of diabetics, resulting in 82,000 lower
      extremity amputations annually; venous leg ulcers affect 0.18% to 1.35% of the
      population; and pressure ulcers are found in 5.0% to 8.8% of institutionalized
      patients and 14.8% of patients in acute care facilities. Despite the large number
      of potential beneficiaries, cellular tissue-engineered products have suffered
      setbacks in recent years and have garnered considerably lower market share than
      commercial promoters anticipated. The mechanism of action of these products is
      not universally agreed upon, but delivery of growth factors and extracellular
      matrix components to the wound is thought to be important; graft "take" is not
      usually considered to occur. These "engineered" products do not specifically
      match a treatment modality to an underlying pathology. Clinical effect is often
      modest, and sometimes not justi- fiable from a cost-benefit perspective.
      Nevertheless, clinical reports in the literature of uses of tissueengineered
      biological dressings continue to mount, indicating that these products are
      finding niche applications where clinical utility is high and the cost can be
      defended. Despite commercial setbacks, the first-approved products, Dermagraft,
      Apligraf, and Cultured Epidermal Autograft (Epicel) are still being marketed, and
      new ones, such as OrCel, continue to be developed. The major indications for
      these products are summarized and a brief review of the available clinical
      literature is offered.

PMID- 16995776
TI  - Regulation of chondrocyte differentiation level via co-culture with osteoblasts.
AB  - The close apposition of osteoblasts and chondrocytes in bone and their
      interaction during bone development and regeneration suggest that they may each
      regulate the other's growth and differentiation. In these studies, osteoblasts
      and chondrocytes were co-cultured in vitro, with both direct and indirect
      contact. Proliferation of the co-cultured chondrocytes was enhanced using soluble
      factors produced from the osteoblasts, and the differentiation level of the
      osteoblasts influenced the differentiation level of the chondrocytes. In
      addition, the chondrocytes regulated differentiation of the co-cultured
      osteoblasts using soluble factors and direct contact. These data support the
      possibility of direct, reciprocal instructive interactions between chondrocytes
      and osteoblasts in a variety of normal processes and further suggest that it may
      be necessary to account for this signaling in the regeneration of complex tissues
      comprising cartilage and mineralized tissue.

PMID- 16995777
TI  - Impact of expansion and redifferentiation conditions on chondrogenic capacity of
      cultured chondrocytes.
AB  - Cartilage regeneration based on isolated and culture-expanded chondrocytes is
      studied in a variety of in vitro models, but with varying morphological quality
      of tissue synthesized. The goal of the present study was to investigate the
      extent of the influence of expansion and redifferentiation conditions on final
      tissue morphology by comparing 2 expansion and redifferentiation methods.
      Chondrocytes from 9 human donors were expanded in medium without growth factor
      supplementation (basic expansion condition [BEC]) or in medium with basic
      fibroblast growth factor (bFGF) supplementation (growth factor supplemented
      expansion condition [GFSEC]). After expansion, cells were either redifferentiated
      in pellet culture or seeded on collagen type II-coated filters. Post-expansion
      mRNA levels of collagen type I and II and Sox-5, -6, and 9, measured by
      semiquantitative real-time polymerase chain reaction (PCR), suggested that
      expansion in GFSEC results in increased dedifferentiation compared to BEC.
      However, after 28 days of redifferentiation culture, morphology of tissue
      synthesized by GFSEC-expanded chondrocytes scored significantly higher on the
      Bern scale compared to BEC (6.4 +/- 0.3 points vs. 4.5 +/- 0.3 points in pellet
      culture and 6.0 +/- 0.4 points vs. 4.5 +/- 0.3 points on collagen-coated filters;
      p < 0.05). Expansion in GFSEC compared to BEC increased proteoglycan (PG)
      synthesis rate at day 9 (4.0-fold in pellet culture and 1.9-fold on collagen
      coated filters; p < 0.01), PG release (6.7-fold in pellet culture and 3.2-fold on
      collagen-coated filters; p < 0.001), and final PG content at day 28 (1.6-fold in
      pellet culture and 1.5-fold on collagen-coated filters; p < 0.05).
      Redifferentiation on collagen-coated filters compared to pellet culture increased
      PG synthesis rate at day 9 (5.2-fold in BEC-expanded chondrocytes and 2.6-fold in
      GFSEC-expanded chondrocytes; p < 0.01), PG release (4.2-fold in BEC-expanded
      chondrocytes and 3.1-fold in GFSECexpanded chondrocytes; p < 0.01), and final PG
      content (1.3-fold in BEC-expanded chondrocytes and 1.9- fold in GFSEC-expanded
      chondrocytes; p < 0.01). Moreover, as visualized via electron microscopy,
      chondrocytes and organization of extracellular matrix cultured on filters was
      more similar to those found for hyaline cartilage. In conclusion, chondrocyte
      expansion in GFSEC and redifferentiation on collagen-coated filters resulted in
      most optimal chondrogenesis.

PMID- 16995778
TI  - Transforming growth factor-beta1 release from a porous electrostatic spray
      deposition-derived calcium phosphate coating.
AB  - This study evaluated the utilization of a porous coating, derived with
      electrostatic spray deposition (ESD), as a carrier material for transforming
      growth factor-beta1 (TGF-beta1). A porous beta-tricalcium phosphate coating was
      deposited with ESD, and 10 ng of (125) I-labeled TGF-beta1 was loaded on the
      substrates. A burst release during the first hour of incubation of >90% was
      observed, in either culture medium or phosphate-buffered saline (PBS). Ninety
      nine percent of the growth factor was released after 10 days of incubation. All
      samples were able to inhibit epithelial cell growth, indicating that the growth
      factor had remained bioactive after release. Thereafter, osteoblast-like cells
      were seeded upon substrates with or without 10 ng of TGF-beta1. While
      proliferation of osteoblast-like cells was increased on TGF-beta1-loaded
      substrates, differentiation was inhibited or delayed. In conclusion, a porous ESD
      derived calcium phosphate coating can be used as a carrier material for TGF
      beta1, when a burst release is desired.

PMID- 16995779
TI  - Biodegradable polymer nanofiber mesh to maintain functions of endothelial cells.
AB  - Maintaining functions of endothelial cells in vitro is a prerequisite for
      effective endothelialization of biomaterials as an approach to prevent intimal
      hyperplasia of small-diameter vascular grafts. The aim of this study was to
      design suitable nanofiber meshes (NFMs) that further maintain the phenotype and
      functions of human coronary artery endothelial cells (HCAECs). Collagen-coated
      random and aligned poly(L-lactic acid)-co-poly(epsilon-caprolactone) (P(LLA-CL))
      NFMs were fabricated using electrospinning. Mechanical testing showed that
      tensile modulus and strength were greater for the aligned P(LLA-CL) NFM than for
      the random NFM. Spatial distribution of the collagen in the NFMs was visualized
      by labeling with fluorescent dye. HCAECs grew along the direction of nanofiber
      alignment and showed elongated morphology that simulated endothelial cells in
      vivo under blood flow. Both random and aligned P(LLA-CL) NFMs preserved phenotype
      (expression of platelet endothelial cell adhesion molecule-1, fibronectin, and
      collagen type IV in protein level) and functions (complementary DNA microarray
      analysis of 112 genes relevant to endothelial cell functions) of HCAECs. The
      P(LLA-CL) NFMs are potential materials for tissue-engineered vascular grafts that
      may enable effective endothelialization.

PMID- 16995780
TI  - Collagen-GAG scaffolds grafted onto myocardial infarcts in a rat model: a
      delivery vehicle for mesenchymal stem cells.
AB  - Various cell delivery methods have been investigated for cell transplantation
      treatment of cardiac infarcts. In this study, we investigated a type I collagen
      glycosaminoglycan (GAG) scaffold for the implantation of adult bone marrow
      derived mesenchymal stem cells (MSCs) into the infarcted region in the rat heart.
      The objective was to evaluate the tissue response to collagen-GAG scaffolds
      prepared using 2 cross-linking methods. The left coronary artery of female Wistar
      rats was occluded for 60 min, followed by reperfusion. One week later, the
      infarcted region was implanted with (1) collagen-GAG scaffolds cross-linked by
      dehydrothermal treatment alone (DHT; n = 10); (2) collagen-GAG scaffolds cross
      linked by DHT followed by carbodiimide treatment (EDAC; n = 8); or (3) DHT cross
      linked collagen-GAG scaffolds seeded with bromodeoxyuridine (BrdU)-labeled
      allogeneic MSCs (cell-scaffold; n = 9). Shamoperated rats served as controls (n =
      4). Specimens were harvested 3 weeks after the implantation surgery. The tissue
      response was evaluated histomorphometrically and by immunohistochemistry to track
      the BrdU-labeled MSCs. Most of the DHT cross-linked collagen-GAG scaffolds
      degraded, whereas the scaffolds in the EDAC group appeared to be largely intact.
      There were no signs of acute inflammation in any of the groups. A substantial
      amount of neovascularization was seen in the infarcted region in the implant
      groups and in the scaffolds themselves. BrdU-positive cells appeared both in the
      degraded scaffold and the infarct region. DHT cross-linked collagen-GAG scaffolds
      warrant continued investigation as delivery vehicles for implantation of cells
      into infarcted cardiac tissue.

PMID- 16995781
TI  - Collagen scaffolds reinforced with biomimetic composite nano-sized carbonate
      substituted hydroxyapatite crystals and shaped by rapid prototyping to contain
      internal microchannels.
AB  - The next generation of tissue engineering scaffolds will be made to accommodate
      blood vessels and nutrient channels to support cell survival deep in the interior
      of the scaffolds. To this end, we have developed a method that incorporates
      microchannels to permit the flow of nutrient-rich media through collagen-based
      scaffolds. The scaffold matrix comprises nano-sized carbonate-substituted
      hydroxyapatite (HA) crystals internally precipitated in collagen fibers. The
      scaffold therefore mimics many of the features found in bone. A biomimetic
      precipitation technique is used whereby a collagen membrane separates reservoirs
      of calcium and phosphate solutions. The collision of calcium and phosphate ions
      diffusing from opposite directions results in the precipitation of mineral within
      the collagen membrane. Transmission electron microscopy analysis showed the
      dimension of the mineral crystals to be approximately 180 x 80 x 20 nm,
      indicating that the crystals reside in the intermicrofibril gaps. Electron
      diffraction indicated that the mineral was in the HA phase, and infrared
      spectroscopy confirmed type A carbonate substitution. The collagen-HA membrane is
      then used to make 3-dimensional (3D) scaffolds: the membrane is shredded and
      mixed in an aqueous-based collagen dispersion and processed using the critical
      point drying method. Adjusting the pH of the dispersion to 5.0 before mixing the
      composite component preserved the nano-sized carbonate-substituted HA crystals.
      Branching and interconnecting microchannels in the interior of the scaffolds are
      made with a sacrificial mold manufactured by using a 3D wax printer. The 3D wax
      printer has been modified to print the mold from biocompatible materials.
      Appropriately sized microchannels within collagen-HA scaffolds brings us closer
      to fulfilling the mass transport requirements for osteogenic cells living deep
      within the scaffold.

PMID- 16995782
TI  - Using dihydropyridine-release strategies to enhance load effects in engineered
      human bone constructs.
AB  - We report on the development of a novel biodegradable scaffold capable of
      enhancing mechanical signals for tissue-engineering applications. It has been
      shown that mechanotransduction enhances bone formation in vitro and in vivo; in
      tissue-engineering applications, this phenomenon is exploited through the use of
      mechanical bioreactors to generate bone tissue. The dihydropyridine agonist Bay
      K8644 (Bay) acts to increase the opening time of mechanosensitive voltage
      operated calcium channels (VOCCs), specifi- cally L-type VOCCs, which are known
      to play a fundamental role in the early mediation of mechanotransduction. We have
      produced porous 3-dimensional, Bay-encapsulated biodegradable poly(L-lactide)
      acid scaffolds using a solvent-casting and salt-leaching technique. The effects
      of the released Bay on osteoid production and mineralization in human bone cell
      seeded constructs following incubation in a perfusion-compression bioreactor in
      vitro was investigated using Western blotting techniques and a calcium assay
      protocol developed in our lab. Our newly developed scaffolds act by slowly
      releasing the calcium channel agonist Bay K8644 as observed using ultraviolet
      spectroscopy, maintaining the open state of mechanosensitive VOCCs responding to
      load, which augments the load signal at sites of strain across the scaffold. Our
      results demonstrate that, in the presence of physiological loading regimes in
      vitro, release of Bay enhances collagen I protein production and osteoid
      calcification more than non-Bay control constructs do. Osteopontin and
      alpha2delta1 VOCC subunit protein levels were also higher as a result of
      perfusion-compression conditioning. These results indicate that Bay-encapsulated
      scaffolds can be used in the presence of load to enhance the production of load
      bearing engineered tissue.

PMID- 16995783
TI  - Acellular biological tissues containing inherent glycosaminoglycans for loading
      basic fibroblast growth factor promote angiogenesis and tissue regeneration.
AB  - It was found in our previous study that acellular tissues derived from bovine
      pericardia consist primarily of insoluble collagen, elastin, and tightly bound
      glycosaminoglycans (GAGs). It is speculated that the inherent GAGs in acellular
      tissues may serve as a reservoir for loading basic fibroblast growth factor
      (bFGF) and promote angiogenesis and tissue regeneration. This study was therefore
      designed to investigate effects of the content of GAGs in acellular bovine
      pericardia on the binding of bFGF and its release profile in vitro while its
      stimulation in angiogenesis and tissue regeneration in vivo were evaluated
      subcutaneously in a rat model. To control the content of GAGs, acellular tissues
      were treated additionally with hyaluronidase for 1 (Hase-D1), 3 (Hase-D3), or 5
      days (Hase-D5). The in vitro results indicated that a higher content of GAGs in
      the acellular tissue resulted in an increase in bFGF binding and in a more
      gradual and sustained release of the growth factor. The in vivo results obtained
      at 1 week postoperatively showed that the density and the depth of neo-vessels
      infiltrated into the acellular tissue loaded with bFGF (acellular/bFGF) were
      significantly greater than the other test samples. At 1 month postoperatively,
      vascularized neo-connective tissues were found to fill the pores within each test
      sample, particularly for the acellular/bFGF tissue. These results suggested that
      the sustained release of bFGF from the acellular/ bFGF tissue continued to be
      effective in enhancing angiogenesis and generation of new tissues. In conclusion,
      the inherent GAGs present in acellular tissues may be used for binding and
      sustained release of bFGF to enhance angiogenesis and tissue regeneration.

PMID- 16995784
TI  - Prediction of the optimal mechanical properties for a scaffold used in
      osteochondral defect repair.
AB  - The optimal mechanical properties of a scaffold to promote cartilage generation
      in osteochondral defects in vivo are not known. During normal daily activities
      cartilage is subjected to large cyclic loads that not only facilitate nutrient
      transport and waste removal through the dense tissue but also act as a stimulus
      to the chondrocytes. In contrast, cartilage tissue is commonly engineered in
      vitro in a static culture; hence, in many cases, the properties of scaffolds have
      been tailored to suit this in vitro environment. In this study, a
      mechanoregulation algorithm for tissue differentiation was used to determine the
      influence of scaffold material properties on chondrogenesis in a finite element
      model of an osteochondral defect. It is predicted that increasing the stiffness
      of the scaffold increases the amount of cartilage formation and reduces the
      amount of fibrous tissue formation in the defect, but this only holds true up to
      a certain threshold stiffness above which the amount of cartilage formed is
      reduced. Reducing the permeability of the scaffold was also predicted to be
      beneficial. Considering a nonhomogeneous scaffold, an optimal design was
      determined by parametrically varying the mechanical properties of the scaffold
      through its depth. The Young's modulus reduced nonlinearly from the superficial
      region through the depth of the scaffold, while the permeability of the scaffold
      was lowest in the superficial region. As tissue engineering moves from a science
      toward a product, engineering design becomes more relevant, and predictive models
      such as that presented here can provide a scientific basis for design choices.

PMID- 16995785
TI  - Co-culture of bone marrow fibroblasts and endothelial cells on modified
      polycaprolactone substrates for enhanced potentials in bone tissue engineering.
AB  - The creation of a vascularized bed makes the survival of seeded cells on 3
      dimensional scaffolds much more likely. However, relying purely on random
      capillary ingrowth into the porous scaffolds from the host may compromise
      vascularization of a scaffold. One solution is to transplant cells capable of
      differentiating into new blood vessels into the scaffolds to accelerate the
      creation of a vascularized scaffold. Because endothelial cells are the key cells
      involved in blood vessel formation, the present study was designed to investigate
      the development of a biomaterial surface that supports endothelial cell
      attachment and proliferation. The subsequent effects of the material surface
      modifications on the differentiation and proliferation of human bone marrow
      derived fibroblasts (HBMFs) when grown in co-culture with a human bone marrow
      endothelial cell line (HBMEC-60) were studied. Endothelialization studies showed
      that the gelatin-coated and hydroxyapatite-coated substrates were superior for
      HBMEC-60 attachment and proliferation to hydrolyzed-only or untreated
      polycaprolactone substrates. Co-culture studies showed that the presence of the
      HBMEC-60 specifically enhanced HBMF cell proliferation and differentiation and
      that this effect was not observed with co-culture with skin fibroblasts. It is
      concluded that the co-culture of endothelial cells with HBMFs could be a
      promising culture system for bone tissue- engineering applications.

PMID- 16995786
TI  - Potential for synthesis and degradation of extracellular matrix proteins by valve
      interstitial cells seeded onto collagen scaffolds.
AB  - Matrix remodeling, which involves proteolytic enzymes, such as the matrix
      metalloproteinases (MMPs), is of significant importance with respect to tissue
      engineering a heart valve construct. The ability of valve interstitial cells
      (ICs) to release these enzymes in biological scaffolds and to synthesize their
      own matrix has not been adequately studied, and this has important implications
      for tissue engineering. Cultured human aortic valve ICs were seeded onto a 3
      dimensional type I collagen matrix for 28 days, whereby the presence of the
      remodeling enzymes, MMPs, were determined using immunohistochemistry, and
      detection of extracellular matrix (ECM) gene expression was performed using in
      situ hybridization. The collagenases, stromelysins, and membrane-type MMPs were
      expressed in 1%, 2%, and 5% collagen scaffolds after 28 days, whereas gelatinase
      expression was not observed. In situ hybridization revealed the presence of the
      ECM messenger ribonucleic acid (mRNA) in cells cultured in collagen scaffolds
      however, an increase in all three mRNAs was only detected in the 1% collagen
      scaffolds. The presence of collagenases, stromelysins, and membrane-type MMPs
      indicate that human valve ICs have the capacity to remodel type I collagen
      scaffold and that the genes necessary for synthesizing matrix have been turned on
      within the cells themselves. Scaffold composition also demonstrated differential
      effects onMMPexpression. These observations are of relevance with respect to the
      development of tissue-engineered heart valves.

PMID- 16995787
TI  - Tissue-transplant fusion and vascularization of myocardial microtissues and
      macrotissues implanted into chicken embryos and rats.
AB  - Cell-based therapies and tissue engineering initiatives are gathering clinical
      momentum for next-generation treatment of tissue deficiencies. By using gravity
      enforced self-assembly of monodispersed primary cells, we have produced adult and
      neonatal rat cardiomyocyte-based myocardial microtissues that could optionally be
      vascularized following coating with human umbilical vein endothelial cells
      (HUVECs). Within myocardial microtissues, individual cardiomyocytes showed native
      like cell shape and structure, and established electrochemical coupling via
      intercalated disks. This resulted in the coordinated beating of microtissues,
      which was recorded by means of a multi-electrode complementary metal-oxide
      semiconductor microchip. Myocardial microtissues (microm3 scale), coated with
      HUVECs and cast in a custom-shaped agarose mold, assembled to coherent
      macrotissues (mm3 scale), characterized by an extensive capillary network with
      typical vessel ultrastructures. Following implantation into chicken embryos,
      myocardial microtissues recruited the embryo's capillaries to functionally
      vascularize the rat-derived tissue implant. Similarly, transplantation of rat
      myocardial microtissues into the pericardium of adult rats resulted in time
      dependent integration of myocardial microtissues and co-alignment of implanted
      and host cardiomyocytes within 7 days. Myocardial microtissues and custom-shaped
      macrotissues produced by cellular self-assembly exemplify the potential of
      artificial tissue implants for regenerative medicine.

PMID- 16995788
TI  - The effect of platelet-rich plasma on the bone healing around calcium phosphate
      coated and non-coated oral implants in trabecular bone.
AB  - The effect of local application of autologous platelet-rich plasma (PRP) on bone
      healing in combination with the use of titanium implants with 2 different surface
      configurations was investigated. PRP fractions were obtained from venous blood
      sample of 6 goats and applied via gel preparation and subsequent installation in
      the implant site or via dipping of the implant in PRP liquid before insertion.
      Thirty-six implants (18 non-coated and 18 calcium phosphate (CaP) coated) were
      placed into the goat femoral condyles (trabecular bone). The animals were
      sacrificed at 6 weeks after implantation, and implants with surrounding tissue
      were processed for light microscopical evaluation. In addition to subjective
      description of the histological findings, histomorphometrical variables were also
      evaluated (the bone-implant contact and the bone mass adjacent to the implant).
      Significantly more interfacial bone-to-implant contact was observed for all 3
      groups of CaP-coated implants and the titanium / liquid group (non-coated implant
      with PRP liquid) than for the other 2 non-coated titanium groups (with PRP gel or
      without PRP). The evaluation of the bone mass close to implant surface indicated
      that all the groups induced a significant increase of the bone mass except the
      PRP gel groups. On the basis of the observations, it was concluded that magnetron
      sputtered CaP coatings can improve the integration of oral implants in trabecular
      bone. The additional use of PRP did not offer any significant effect on the bone
      response to the CaP-coated implants, whereas PRP in a liquid form showed a
      significant effect on bone apposition to roughened titanium implants during the
      early post-implantation healing phase.

PMID- 16995789
TI  - Auxiliary liver organ formation by implantation of spleen-encapsulated
      hepatocytes.
AB  - Hepatocyte transplantation is an attractive alternative to orthotopic liver
      transplantation. However, its application has been limited because of its short
      term success only. Here we report a new approach to hepatocyte transplantation
      resulting in the generation of an auxiliary liver in vivo. Isolated primary
      hepatocytes were encapsulated in isolated spleens and then transplanted by
      attaching the spleens to the livers of recipient animals (mice or rats) using
      biodegradable adhesive. A vascular network was rapidly established, and protein
      molecules circulated freely between the transplanted spleen and the liver, to
      which they adhered. In contrast, the spleen, which did not adhere to the liver or
      adhered elsewhere (adipose tissue or peritoneum), did not become vascularized but
      shrank and died. Encapsulation of hepatocytes in an isolated spleen enhanced
      their survival significantly, and co-encapsulation of Engelbreth- Holm-Swarm gel
      together with the hepatocytes further enhanced it. The encapsulated hepatocytes
      expressed liver-specific differentiation genes for more than 3 weeks. Plasma
      albumin concentrations in Nagase analbuminemic rats began to increase 3 days
      after transplantation. The transplanted hepatic cells migrated into the liver
      parenchyma, whereas the spleen was absorbed. Thus, we have developed a novel,
      simple approach for the rapid and efficient formation of functional auxiliary
      liver using a modified hepatocyte transplantation method.

PMID- 16995790
TI  - The effects of isolation on chondrocyte gene expression.
AB  - Tissue engineering of articular cartilage usually requires the isolation and
      culture of chondrocytes. Previous studies have suggested that enzymatic isolation
      may alter the metabolic activity and growth rate of chondrocytes. This study
      examined the effects of 4 common isolation protocols on chondrocyte gene
      expression, morphology, and total cell yield immediately following the digest (t
      = 0) and after 2 culture periods (24 h and 1 week). Cartilage explants were
      digested using 1 of 4 protocols: (1) 6-h collagenase digest, (2) 22-h collagenase
      digest, (3) 45-min trypsin digest followed by a 3-h collagenase digest, or (4)
      1.5-h pronase digest followed by a 3-h collagenase digest. Gene expression levels
      for glyceraldehyde-3-phosphate dehydrogenase, type I collagen, type II collagen,
      aggrecan, superficial zone protein, matrix metalloproteinase- 1, and tissue
      inhibitor of metalloproteinase-1 were measured at t = 0 h, 24 h, and 1 week using
      quantitative reverse transcriptase-polymerase chain reaction. In this study, cell
      yield was greatest for the 22-h collagenase and pronase-collagenase digests.
      However, the data indicate that a 6-h collagenase digest has the fewest gene
      expression changes compared to native cells. For tissue engineering, data from
      this study suggest that when cell yield is critical, a 22-h collagenase digest is
      preferable, but when obtaining cells closest to native chondrocytes is more
      desired, the 6-h collagenase digest is more beneficial.

PMID- 16995791
TI  - hCTLA4-gene modified human bone marrow-derived mesenchymal stem cells as
      allogeneic seed cells in bone tissue engineering.
AB  - Immune rejection of heterogeneic seed cells, even of low antigenicity human bone
      marrow derived mesenchymal stem cells (hBMMSCs), remains an obstacle for bone
      tissue engineering. It is still a question how to transfer the gene of human
      cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig), a well-known ligand
      for CD80/CD86, to hBMMSCs to prolong survival time while not interfering with
      their osteogenesis in vivo. Our data, for the first time, clearly demonstrate
      that CTLA4-Ig gene modified hBMMSCs could normally differentiate to osteoblasts
      in vitro, significantly inhibit immune response in the model of mixed lymphocyte
      culture, and survive until bone tissue formed in vivo. Thus, CTLA4Ig gene
      modified hBMMSCs might be promising seed cells for bone tissue engineering.

PMID- 16995792
TI  - Characterization of 75:25 poly(l-lactide-co-epsilon-caprolactone) thin films for
      the endoluminal delivery of adipose-derived stem cells to abdominal aortic
      aneurysms.
AB  - Abdominal aortic aneurysms occur in 5-7% of men over the age of 60 and their
      incidence is rising. Current therapies remove the affected tissue or prevent
      blood flow through the aneurysm, but do not repair the underlying structural
      changes of the vascular wall. Adipose tissue derived stem cells (ADSCs) seeded on
      a biodegradable thin film and delivered endoluminally to the aneurysm site could
      potentially repair the vessel wall, preventing growth and rupture of the
      aneurysm. In this study, the mechanical and degradation properties of a novel
      75:25 poly(l-lactide-co-epsilon-caprolactone) (PLCL) thin film, as well as, the
      effects of different surface structures on stem cell adherence and resistance to
      shear stress was investigated. It was possible to reproducibly create films of
      consistent physical properties. These films degraded approximately 50% in 6
      month, which would be a sufficient time to allow cells to engraft in the aortic
      wall. Ethylene oxide treatment significantly increased the stiffness and yield
      stress of the films, which exhibit >700% elongation. Treatment of the films with
      NaOH and HCl induced the formation of surface texture on the films; however, this
      texture did not affect stem cell adherence or resistance to delamination by shear
      stress when compared to nontreated or fibronectin-coated films. These results
      indicate that PLCL thin films have a sufficient degradation time and mechanical
      strength to serve as a scaffold in vivo for ADSCs, and that ADSCs seeded on the
      thin film can withstand a range of physiologic shear stresses.

PMID- 16995793
TI  - Novel geometries for tissue-engineered tendonous collagen constructs.
AB  - A promising approach to addressing the performance limitations of currently
      available mechanical and bioprosthetic heart valves lies in tissue engineering.
      Tissue-engineered valves should incorporate the complex microstructure of the
      native valves to mimic their unique mechanics. This would include a layered
      topology, mesh networks, and branched collagen fiber bundles. Our approach to
      heart valve tissue engineering is to develop the functional components of the
      aortic valve cusps separately in vitro and, once they are mature, integrate them
      into a composite valve structure. Here we report on our efforts to create more
      complex collagenous structures, suitable for heart valve tissue engineering.
      Collagen fiber bundles were fabricated using the principle of directed collagen
      gel contraction, using neonatal rat aortic smooth muscle cells and acid-soluble
      type I rat-tail tendon collagen. The collagen gels were cast into rectangular or
      branched wells with porous end holders that constrained the gels longitudinally
      but allowed contraction to occur transverse to the long axis. Pairs of such
      constructs were placed in direct contact with each other and cultured further to
      determine whether they integrated to form continuous tissue. After 6-8 weeks of
      culture, highly compacted and aligned collagen fiber bundles formed. Mechanical
      testing revealed that linear constructs (2 free ends) with an 8:1 aspect ratio
      were significantly stronger than similar constructs with an aspect ratio of 2:1
      (mean +/- SD, 298 +/- 90 kPa vs. 152 +/- 49 kPa; p < .001). Branching reduced
      mechanical strength considerably. Constructs fabricated with 4 free ends were
      significantly weaker than constructs with 3 ends (31 +/- 32 kPa vs. 116 +/- 66
      kPa; p < .003). Histologic images demonstrated the integration of the crossed
      collagen bundles, with a bonding strength of 2.1 +/- 1.1 g (0.02 N). We found
      that the geometry of the molds into which the collagen constructs are cast can
      greatly affect their mechanical strength: multibranched constructs were the
      weakest, and long, linear constructs were the strongest. We also found that
      integration of collagen constructs occurs in vitro and that the fabrication of a
      composite structure in vitro is probably feasible.

PMID- 16995794
TI  - Gene regulation ex vivo within a wrap-around tendon.
AB  - This study tested the hypothesis that physiologic tendon loading modulates the
      fibrous connective tissue phenotype in undifferentiated skeletal cells. Type I
      collagen sponges containing human bone marrow stromal cells (MSCs) were implanted
      into the midsubstance of excised sheep patellar tendons. An ex vivo loading
      system was designed to cyclically stretch each tendon from 0 to 5% at 1.0 Hz. The
      MSC-sponge constructs were implanted into 2 tendon sites: the first site
      subjected to tension only and a second site located at an artificially created
      wrap-around region in which an additional compressive stress was generated
      transverse to the longitudinal axis of the tendon. The induced contact pressure
      at the wraparound site was 0.55 +/- 0.12 MPa, as quantified by pressure-sensitive
      film. An MSC-sponge construct was maintained free swelling in the same bath as an
      unloaded control. After 2 h of tendon stretching, the MSC-sponge constructs were
      harvested and real-time PCR was used to quantify Fos, Sox9, Cbfa1 (Runx2), and
      scleraxis mRNA expression as markers of skeletal differentiation. Two hours of
      mechanical loading distinctly altered MSC differentiation in the wrap-around
      region and the tensile-only region, as evidenced by differences in Fos and Sox9
      mRNA expression. Expression of Fos mRNA was 13 and 52 times higher in the tensile
      only and wrap-around regions, respectively, compared to the free-swelling
      controls. Expression of Sox9 mRNA was significantly higher (2.5-3 times) in MSCs
      from the wraparound region compared to those from the tensile-only region or in
      free-swelling controls. In contrast, expression levels for Cbfa1 did not differ
      among constructs. Scleraxis mRNA was not detected in any construct. This study
      demonstrates that the physiologic mechanical environment in the wrap-around
      regions of tendons provides stimuli for upregulating early response genes and
      transcription factors associated with chondrogenic differentiation. These
      differentiation responses begin within as little as 2 h after the onset of
      mechanical stimulation and may be the basis for the formation of fibrocartilage
      that is typically found in the wrap-around region of mature tendons in vivo.

PMID- 16995795
TI  - Effect of fibroblasts on tracheal epithelial regeneration in vitro.
AB  - Several artificial grafts for covering deficient trachea have been produced
      through tissue engineering. Recently, our group clinically used an artificial
      trachea made from collagen sponge for patients with noncircumferential tracheal
      resection. However, the slowness of epithelial regeneration on the surface of the
      artificial trachea was confirmed as one particular problem. In this study, we co
      cultured tracheal epithelial cells with fibroblasts and examined effects of
      fibroblasts on epithelial regeneration in vitro. Fibroblasts activated epithelial
      cell proliferation and migration. In co-culture with fibroblasts, epithelial
      cells reconstructed pseudostratified epithelium, which was composed of ciliated,
      goblet, and basal cells. Furthermore, a basement membrane was reconstructed
      between epithelial cells and fibroblasts, and integrin beta4 was also observed
      there. Fibroblasts rapidly increased mucin secretion by epithelial cells. These
      results indicate that stimulatory effects of fibroblasts on epithelial cell
      migration, proliferation, and differentiation would reduce the time required for
      covering of epithelial cells on the defect of luminal surface and hasten
      regeneration of morphologically and functionally normalized epithelium involving
      the reconstruction of basement membrane.

PMID- 16995796
TI  - Transplantation of an autologous mesothelial cell sheet prepared from tunica
      vaginalis prevents post-operative adhesions in a canine model.
AB  - Post-operative adhesions often cause severe complications such as bowel
      obstruction and abdominopelvic pain. Previously, we reported that transplantation
      of a mesothelial cell sheet is effective for preventing adhesion in rat model. We
      also proposed a new technique for harvesting autologous mesothelial cells from
      tunica vaginalis without intra-abdominal maneuvers. In this study, we examined
      whether an autologous mesothelial cell sheet can prevent post-operative
      peritoneal adhesions in a canine adhesion model. Mesothelial cells were isolated
      from the tunica vaginalis of male beagles. Isolated cells were cultured on fibrin
      gel. We named this construct the "mesothelial cell sheet." Animals underwent
      surgery to induce peritoneal adhesion formation and were then transplanted with
      the mesothelial cell sheets (sheet group, n = 4), fibrin gel (fibrin group, n =
      4), or no materials (sham group, n = 4). Four weeks after the transplantation, we
      evaluated adhesion formation and scored adhesion levels. The abdominal wall
      transplanted with the mesothelial cell sheet was covered with mesothelium. The
      total adhesion score of the sheet group was significantly lower than that of the
      fibrin group and the sham group. These results indicated that transplantation of
      an autologous mesothelial cell sheet is effective for preventing post-operative
      adhesion formation in the canine adhesion model. Our mesothelial cell sheet has
      the potential to be a powerful adhesion prophylactic material in surgery.

PMID- 16995797
TI  - Suppression of genes related to hypertrophy and osteogenesis in committed human
      mesenchymal stem cells cultured on novel nitrogen-rich plasma polymer coatings.
AB  - Mesenchymal stem cells (MSCs) are pluripotent progenitor cells with the ability
      to generate cartilage, bone, muscle, tendon, ligament, and fat. However, recent
      evidence indicates that a major drawback of current cartilage- and intervertebral
      disc-tissue engineering is that human MSCs isolated from some arthritic patients
      (a clinically relevant source of stem cells) express type X collagen (a marker of
      chondrocyte hypertrophy associated with endochondral ossification) and osteogenic
      markers. Some studies have attempted to use growth factors to inhibit type X
      collagen expression, but none has addressed the possible effect of the chemical
      composition of the substratum on chondrocyte hypertrophy and osteogenesis. Here,
      we examine the growth and differentiation potential of human MSCs cultured on
      nitrogen (N)-rich plasma polymer layers (N-doped plasma-polymerized ethylene,
      containing up to 36% nitrogen; PPE:N). We show that PPE:N almost completely
      suppresses the expression not only of type X collagen, but also of osteogenic
      marker genes such as alkaline phosphatase, bone sialoprotein, and osteocalcin. In
      contrast, neither aggrecan nor type I collagen expression were significantly
      affected. These results indicate that PPE:N coatings may be suitable surfaces for
      inducing MSCs to a chondrocyte or disc-like phenotype for tissue engineering of
      cartilage or intervertebral discs, in which hypertrophy and osteogenesis are
      suppressed.

PMID- 16995798
TI  - Two techniques for the preparation of cell-scaffold constructs suitable for sinus
      augmentation: steps into clinical application.
AB  - The objective of this clinical trial was the analysis of 2 methods for
      engineering of autologous bone grafts for maxillary sinus augmentation with
      secondary implant placement. Group 1 (8 patients, 12 sinuses): cells of
      mandibular periosteum were cultured in a good manufacturing practice laboratory
      (2 weeks) with autologous serum and then transferred onto a collagen matrix.
      After another week, these composites were transplanted into the sinuses. In group
      2A (2 patients, 3 sinuses), cells of maxillary bone were cultivated with
      autologous serum for 2 weeks, seeded onto natural bone mineral (NBM, diameter [O]
      = 8 mm) blocks, and cultivated for another 1.5 months. These composites were
      transplanted into the sinuses. Group 2B (control, 3 patients, 5 sinuses) received
      NBM blocks alone. In the course of implant placement 6 (group 1) and 8 (group 2)
      months later, core biopsy were taken. Clinical follow-up period was 1 to 2.5
      years in group 1 and approximately 7 years in groups 2A and 2B. New vital bone
      was found in all cases at median densities of 38% (n = 12) in group 1, 32% in
      group 2A (n = 3), and 25% in group 2B (n = 5). Differences between group 1 and 2B
      as well as 2A and 2B were statistically significant ( p = 0.025). No adverse
      effects were seen. All methods described were capable of creating new bone tissue
      with sufficient stability for successful implant placement.

PMID- 16995799
TI  - Controlled in vivo degradation of genipin crosslinked polyethylene glycol
      hydrogels within osteochondral defects.
AB  - Polyethylene glycol (PEG) hydrogels show promise as scaffolds for growth factor
      delivery to enhance cartilage repair. However, methods to control growth factor
      release in vivo are needed. We have recently shown that in vitro polymer
      degradation and in vitro growth factor release kinetics can be altered using PEG
      crosslinked with different concentrations of genipin. However, the degradation
      and behavior of PEG-genipin in vivo within the cartilage repair site are unknown.
      This study was conducted to test the hypotheses that the degradation of PEG
      genipin can be altered in vivo within osteochondral defects by changing the
      concentration of genipin, and that PEG-genipin is biocompatible within the
      mammalian diarthrodial environment. PEG-genipin cylindrical polymers crosslinked
      using 8mM, 17.6 mM, or 35.2 mM of genipin were implanted into osteochondral
      defects made in the trochlea of 24 male Sprague- Dawley rats (48 knees). Rats
      were sacrificed at 5 weeks and gross, cross-sectional, and histologic assessments
      were performed. Altering the genipin concentration changed the in vivo
      degradation properties of the hydrogel ( p < 0.01). Consistent with in vitro
      findings, polymer degradation was inversely related to the concentration of
      genipin. Near-complete degradation was seen at 8 mM, intermediate degradation at
      17.6 mM, and minimal degradation at 35.2 mM. The results of this study show the
      degradation of PEGgenipin can be altered in vivo within osteochondral defects by
      changing the concentration of genipin and that PEG-genipin is biocompatible
      within osteochondral defects. This new in vivo data support potential use of PEG
      genipin polymer as an innovative delivery system to control in vivo release of
      growth factors for improving articular cartilage repair.

PMID- 16995800
TI  - Effects of auricular chondrocyte expansion on neocartilage formation in
      photocrosslinked hyaluronic acid networks.
AB  - The overall objective of this study was to examine the effects of in vitro
      expansion on neocartilage formation by auricular chondrocytes photoencapsulated
      in a hyaluronic acid (HA) hydrogel as a next step toward the clinical application
      of tissue engineering therapies for treatment of damaged cartilage. Swine
      auricular chondrocytes were encapsulated either directly after isolation (p = 0),
      or after further in vitro expansion ( p = 1 and p = 2) in a 2 wt%, 50-kDa HA
      hydrogel and implanted subcutaneously in the dorsum of nude mice. After 12 weeks,
      constructs were explanted for mechanical testing and biochemical and
      immunohistochemical analysis and compared to controls of HA gels alone and native
      cartilage. The compressive equilibrium moduli of the p = 0 and p = 1 constructs
      (51.2 +/- 8.0 and 72.5 +/- 35.2 kPa, respectively) were greater than the p = 2
      constructs (26.8 +/- 14.9 kPa) and the control HA gel alone (12.3 +/- 1.3 kPa)
      and comparable to auricular cartilage (35.1 +/- 12.2 kPa). Biochemical analysis
      showed a general decrease in glycosaminoglycan (GAG), collagen, and elastin
      content with chondrocyte passage, though no significant differences were found
      between the p = 0 and p = 1 constructs for any of the analyses. Histological
      staining showed intense and uniform staining for aggrecan, as well as greater
      type II collagen versus type I collagen staining in all constructs. Overall, this
      study illustrates that constructs with the p = 0 and p = 1 auricular chondrocytes
      produced neocartilage tissue that resembled native auricular cartilage after 12
      weeks in vivo. However, these results indicate that further expansion of the
      chondrocytes (p = 2) can lead to compromised tissue properties.

PMID- 16995801
TI  - Tissue engineering of a small hand phalanx with a porously casted polylactic acid
      polyglycolic acid copolymer.
AB  - In this study, we evaluate a porous polylactic acid-polyglycolic acid (PLGA)
      polymer in tissue engineering a small hand phalanx. The PLGA polymer was
      processed with a unique solvent cast/salt-leaching method in the shape of a
      little finger distal phalanx. An 85% polylactic acid (PLA)/15% polyglycolic acid
      (PGA) copolymer was determined to be the most favorable mixture for creating a
      small digital phalanx in precise shape and size. The pore sizes averaged 250-425
      microm. Bovine periosteum was wrapped around each phalangeal polymer.
      Chondrocytes were injected into the articular end. Six constructs were surgically
      placed into a dorsal subcutaneous pocket of an ethylic mouse. After 8 (n=2) or 16
      (n = 4) weeks, all implants demonstrated growth of bone and cartilage in the
      shape and size of a small hand phalanx, which was maintained throughout the study
      period. Histologic evaluation showed a homogeneous presence of bone and
      cartilage, with progressive tissue differentiation and matrix production from 8
      to 16 weeks. The tissue-engineered bone formed through an endochondral
      ossification process. Articular cartilage was maintained where the chondrocytes
      were placed. These findings suggest that the porous PLGA polymer is an effective
      synthetic biodegradable device to support and guide tissue growth of bone and
      articular cartilage in the shape of a human phalanx.

PMID- 16995802
TI  - Endothelial cells assemble into a 3-dimensional prevascular network in a bone
      tissue engineering construct.
AB  - To engineer tissues with clinically relevant dimensions, one must overcome the
      challenge of rapidly creating functional blood vessels to supply cells with
      oxygen and nutrients and to remove waste products. We tested the hypothesis that
      endothelial cells, cocultured with osteoprogenitor cells, can organize into a
      prevascular network in vitro. When cultured in a spheroid coculture model with
      human mesenchymal stem cells, human umbilical vein endothelial cells (HUVECs)
      form a 3-dimensional prevascular network within 10 days of in vitro culture. The
      formation of the prevascular network was promoted by seeding 2% or fewer HUVECs.
      Moreover, the addition of endothelial cells resulted in a 4-fold upregulation of
      the osteogenic marker alkaline phosphatase. The addition of mouse embryonic
      fibroblasts did not result in stabilization of the prevascular network. Upon
      implantation, the prevascular network developed further and structures including
      lumen could be seen regularly. However, anastomosis with the host vasculature was
      limited. We conclude that endothelial cells are able to form a 3-dimensional (3D)
      prevascular network in vitro in a bone tissue engineering setting. This finding
      is a strong indication that in vitro prevascularization is a promising strategy
      to improve implant vascularization in bone tissue engineering.

PMID- 16995803
TI  - Chondrogenic differentiation of human embryonic stem cell-derived cells in
      arginine-glycine-aspartate-modified hydrogels.
AB  - Human embryonic stem cells (hESCs) have the potential to self-renew and generate
      multiple cell types, producing critical building blocks for tissue engineering
      and regenerative medicine applications. Here, we describe the efficient
      derivation and chondrogenic differentiation of mesenchymal-like cells from hESCs.
      These cells exhibit mesenchymal stem cell (MSC) surface markers, including CD29,
      CD44, CD105, and platelet-derived growth factor receptor-alpha. Under appropriate
      growth conditions, the hESC-derived cells proliferated without phenotypic changes
      and maintained MSC surface markers. The chondrogenic capacity of the cells was
      studied in pellet culture and after encapsulation in poly(ethylene glycol)
      diacrylate (PEGDA) hydrogels with exogenous extracellular proteins or
      arginineglycine- aspartate (RGD)-modified PEGDA hydrogels. The hESC-derived cells
      exhibited growth factor- dependent matrix production in pellet culture but did
      not produce tissue characteristic of cartilage morphology. In PEGDA hydrogels
      containing exogenous hyaluronic acid or type I collagen, no significant cell
      growth or matrix production was observed. In contrast, when these cells were
      encapsulated in RGDmodified poly(ethylene glycol)hydrogels, neocartilage with
      basophilic extracellular matrix deposition was observed within 3 weeks of
      culture, producing cartilage-specific gene up-regulation and extracellular matrix
      production. Our results indicate that precursor cells characteristic of a MSC
      population can be cultured from differentiating hESCs through embryoid bodies,
      thus holding great promise for a potentially unlimited source of cells for
      cartilage tissue engineering.

PMID- 16995804
TI  - Osteonecrosis of the jaw: more research needed.

PMID- 16995805
TI  - Rickets in the 17th century.
AB  - Rickets was first documented as a cause of death in the Bills of Mortality for
      The City of London in 1634, but detailed descriptions were only published between
      1645 and 1668. It was thought at the time that this was a new disease in England,
      but there was no indication as to the cause of the condition. However, air
      pollution from smoke produced by burning coal caused serious problems at that
      time, and so it can be suggested that vitamin D deficiency was responsible.

PMID- 16995807
TI  - Genomic regions identified for BMD in a large sample including epistatic
      interactions and gender-specific effects.
AB  - A genome-wide linkage scan was conducted using a large white sample to identify
      QTLs for BMD. We found QTLs in the total sample and the gender-specific
      subgroups, as well as significant epistatic interactions underlying BMD
      variations. INTRODUCTION: Low BMD is an important risk factor for osteoporosis
      and under strong genetic control. MATERIALS AND METHODS: To identify quantitative
      trait loci (QTLs) for regulation of BMD, we performed a large-scale whole genome
      linkage scan (WGS) involving 4126 individuals from 451 families. In addition to
      the conventional linkage analyses in the total combined sample of males and
      females, we conducted epistatic interaction analyses and gender-specific linkage
      analyses. RESULTS: Significant linkage was detected on 5q23 for wrist BMD (LOD =
      3.39) and 15q13 for female spine BMD (LOD = 4.49). For spine BMD, we revealed
      significant epistatic interactions between 3p25 and 2q32 (p = 0.0022) and between
      3p25 and 11q23 (p = 0.0007). We replicated several genomic regions that showed
      linkage with BMD in previous studies by others and ours, such as 3p21, 1p36, and
      Xq27. CONCLUSIONS: This study highlights the importance of large sample size,
      incorporation of epistatic interaction, and consideration of gender-specific
      effects in identifying QTLs for BMD variation. The results of this study provide
      a foundation for the future fine mapping and gene identification in our
      population.

PMID- 16995808
TI  - Epidemiology of Paget's disease in Europe: the prevalence is decreasing.
AB  - This study estimated changes in the age- and sex-specific prevalence of Paget's
      disease of bone in six European towns over a 20-year period. Declines in
      prevalence were observed in this disorder, occurring among both men and women.
      INTRODUCTION: To estimate secular changes in the age-and sex-specific prevalence
      of Paget's disease of bone in Europe, we conducted a second radiographic survey
      using identical sampling and methods in six European towns where a baseline study
      was performed in 1978-1979. In addition to these towns, the survey was carried
      out in two Hungarian centers not included in the initial study. MATERIALS AND
      METHODS: In each center, a sample of abdominal radiographs of people >or=55 years
      of age was taken from stored films within the radiology department of the
      principal general hospital. Radiographs showing the entire pelvis, sacrum,
      femoral heads, and lumbar vertebrae were studied for the period of 2000-2001. The
      films were evaluated by a trained observer and a consultant radiologist. RESULTS:
      A total of 6935 radiographs (3512 women and 3423 men) were assessed in the eight
      towns. The overall age- and sex-standardized prevalence rate of Paget's disease
      was 0.3% with a male/female ratio of 1.5. Prevalence increased with age among men
      and women rising to 0.8% of men and 0.9% of women >/=85 years of age. The
      differences in prevalence rate among the European centers were relatively small,
      especially in women. There was a decline in rates between 1978/79 and 2000/01.
      CONCLUSIONS: These European data confirm the decrease in frequency of Paget's
      disease observed in Britain. These declines favor an environmental contribution
      to the causation of the disease that requires further research.

PMID- 16995809
TI  - BMD and risk of hip and nonvertebral fractures in older men: a prospective study
      and comparison with older women.
AB  - In a prospective study of 5384 older men, hip BMD was a very strong predictor of
      hip fracture, much stronger than spine BMD. The relationship between hip BMD and
      hip fracture risk seemed to be stronger than observed in a large prospective
      study of women. Hip BMD is an excellent test for predicting fracture risk in men.
      INTRODUCTION: There have been few studies of the relationship between BMD and
      risk of fractures in men and none for the association between lumbar spine BMD
      and risk of hip and nonvertebral fractures. There is also controversy about
      whether the associations between BMD and risk of fracture are the same in men and
      women. MATERIALS AND METHODS: We measured proximal femur and lumbar spine BMD in
      5384 men, 5384 men, >or= 65 years of age. We compared the results to the very
      similar cohort of 7871 women >or=65 of age. During 4.4 years of 99% complete
      follow-up, we validated 317 nonvertebral (59 hip) fractures in men and 1169
      nonvertebral (208 hip) fractures in women. RESULTS: Total hip BMD was very
      strongly associated with risk hip fracture in men (3.2-fold increased risk per
      sex-specific SD decrease in BMD; 95% CI, 2.4-4.1). The association was stronger
      than observed in SOF (2.1; 95% CI, 1.8, 2.4; p < 0.001 for interaction). Among
      the men, lumbar spine BMD was weakly associated with risk of hip fracture
      (relative risk [RR] per sex-specific SD decrease in BMD: 1.5; 95% CI, 1.2, 2.0).
      The association between total hip BMD and risk of nonvertebral fractures was
      somewhat stronger for men (RR = 1.6; 95% CI, 1.5, 1.8) than found for women (p =
      0.01 for interaction). The risk of nonvertebral fracture was substantially higher
      in women than in men for all T scores of hip BMD, regardless of whether sex
      specific or female reference values were used. CONCLUSIONS: Hip BMD is strongly
      associated with risk of nonvertebral, and especially hip fracture, in older men.
      These associations are at least as strong as in women. As in women, lumbar spine
      BMD in men is only weakly associated with risk of hip fracture. Regardless of
      whether sex-specific or female reference values were used, T scores indicated
      different risks of fractures in men than in women.

PMID- 16995810
TI  - Association between prior non-spine non-hip fractures or prevalent radiographic
      vertebral deformities known to be at least 10 years old and incident hip
      fracture.
AB  - In this large cohort of elderly women, prior non-spine non-hip fractures and
      radiographic vertebral deformities >10 years old were modestly associated with
      incident hip fracture, but the excess risks of hip fracture attributable to those
      prior fractures and deformities seem to wane over time. INTRODUCTION: Whereas
      prior clinical fractures and prevalent radiographic vertebral deformities are
      well-documented predictors of incident hip fracture, the excess risks of incident
      fractures attributable to those prior fractures and deformities may decrease over
      time. Current guidelines regarding the assessment of fracture risk do not
      consider elapsed time since prior fracture or ascertainment of radiographic
      vertebral deformity. MATERIALS AND METHODS: We ascertained self-reported history
      of prior clinical fractures and calcaneal and total hip bone BMD and performed
      lateral spine radiographs in a cohort of 9516 community-dwelling elderly women
      who had not had a prior hip fracture. We prospectively followed them to assess
      incident hip fracture. Prevalent radiographic vertebral deformities were
      identified at baseline using morphometry, and incident hip fractures were
      confirmed by review of radiographic reports during three follow-up periods (0-5,
      >5-10, and >10 years after baseline exam). RESULTS: Among women who survived for
      10 or more years after the baseline exam without having had a hip fracture, a
      history of non-spine non-hip fracture since age 50 reported at the baseline study
      examination was associated with a 21% age- and calcaneal BMD-adjusted excess risk
      (hazard ratio [HR], 1.21; 95% CI, 1.01-1.45) for subsequent incident hip
      fracture. Baseline radiographic vertebral deformity was associated with a 41% age
      and BMD-adjusted excess risk (HR, 1.41; 95% CI, 1.15-1.73) of hip fracture after
      10 years of follow-up. In comparison, the age- and BMD-adjusted HRs of incident
      hip fracture during the first 5 years of follow-up associated with prior non
      spine non-hip fractures reported at the baseline study exam and prevalent
      radiographic vertebral deformities were 1.70 (95% CI, 1.30-2.22) and 2.10 (95%
      CI, 1.58-2.78), respectively. CONCLUSIONS: Self-reported prior non-spine non-hip
      fractures and prevalent radiographic vertebral deformities known to be at least
      10 years old are modestly associated with incident hip fracture. The association
      between these predictor fractures and subsequent hip fractures seems to wane with
      increased time after ascertainment of the predictor fracture. Hip fracture risk
      assessment strategies incorporating prior fracture history should also consider
      elapsed time since those prior fractures.

PMID- 16995806
TI  - Molecular genetic studies of gene identification for osteoporosis: a 2004 update.
AB  - This review summarizes comprehensively the most important and representative
      molecular genetics studies of gene identification for osteoporosis published up
      to the end of December 2004. It is intended to constitute a sequential update of
      our previously published review covering the available data up to the end of
      2002. Evidence from candidate gene association studies and genome-wide linkage
      studies in humans, as well as quantitative trait locus mapping animal models are
      reviewed separately. Studies of transgenic and knockout mice models relevant to
      osteoporosis are summarized. An important extension of this update is
      incorporation of functional genomic studies (including DNA microarrays and
      proteomics) on osteogenesis and osteoporosis, in light of the rapid advances and
      the promising prospects of the field. Comments are made on the most notable
      findings and representative studies for their potential influence and
      implications on our present understanding of genetics of osteoporosis. The format
      adopted by this review should be ideal for accommodating future new advances and
      studies.

PMID- 16995811
TI  - Fracture incidence and characterization in patients on osteoporosis treatment:
      the ICARO study.
AB  - None of the available osteoporosis therapies have been shown to completely
      abolish the risk of fractures. In clinical practice, the outcome may be even
      poorer. In 880 patients prescribed with antiresorptives (alendronate,
      risedronate, and raloxifene) for >1 year, a fragility fracture was recorded in
      8.9%/year of them. This incidence is considerably higher than that observed in
      randomized clinical trials, and it was significantly related to poor compliance
      and lack of supplementation with calcium and vitamin D. INTRODUCTION:
      Osteoporotic fracture is one of the most important public health concerns among
      the elderly. Currently available therapies have been shown to significantly
      decrease the risk of fracture, although none of them completely abolishes this
      risk. In clinical practice, poor treatment response may also result from a number
      of other factors. MATERIALS AND METHODS: The Incidence and ChAracterization of
      inadequate clinical Responders in Osteoporosis (ICARO) is a multicenter,
      observational study carried out in Italy. It aimed to analyze, in postmenopausal
      women with established osteoporosis, the risk factors for an "inadequate clinical
      response" to drug therapy, defined as the occurrence of new vertebral or
      nonvertebral fragility fractures in patients prescribed, for at least 1 year,
      alendronate, risedronate, or raloxifene, with a compliance >50%. RESULTS: In 880
      patients treated with antiresorptive agents for a median of 2.0 years (95% CI:
      1.0-4.5) years, the "inadequate clinical responder (ICR)" subjects over the
      observation period were 220 (25%), with an annual incidence of 8.9%. ICRs,
      compared with "adequate clinical responders (ACRs)," had more pretreatment
      fractures and were treated longer (2.8 versus 1.8 years; p < 0.001). After
      multiple adjustment for these confounding factors, significant determinants of
      inadequate clinical response were a poorer treatment compliance and a less
      frequent co-administration of calcium and vitamin D supplements. CONCLUSIONS: The
      incidence of fractures during treatment with antiresorptive agents in a clinical
      setting is considerably higher than that observed in randomized clinical trials.
      Inadequate compliance to treatment and lack of supplementation of calcium and
      vitamin D are major determinants of this poor response.

PMID- 16995812
TI  - Mixed metastatic lung cancer lesions in bone are inhibited by noggin
      overexpression and Rank:Fc administration.
AB  - Lung cancer metastases to bone produce a primarily mixed osteolytic/osteoblastic
      lesion. The purpose of this study was to determine if blockade of both pathways
      would inhibit the formation these lesions in bone. Inhibition of the osteoblastic
      lesion with noggin and the osteolytic lesion with RANK:Fc was a successful
      treatment strategy to inhibit progression of mixed lung cancer lesions in bone.
      INTRODUCTION: Approximately 9-30% of patients with lung cancer develop bone
      metastases, leading to significant morbidity and mortality. A549 is a non-small
      cell lung cancer (NSCLC) line that produces a mixed metastatic lesion in bone. We
      sought to determine if blockade of key components in both osteolytic and
      osteoblastic pathways would result in a reduction of a NSCLC tumor progression in
      a murine model of bony metastasis. MATERIALS AND METHODS: The study used a
      retroviral vector overexpressing noggin (RN), a specific inhibitor of BMP, and
      RANK:Fc, a chimeric protein that inhibits the RANK-RANKL interaction. A549 cells
      were transduced with RN before implantation in SCID mice. Cells were implanted in
      a subcutaneous model and tibial injection model. RANK:Fc was administered twice
      weekly at 15 mg/kg. There were five treatment groups: A549; A549 + RN; A549 +
      RANK:Fc; A549 + empty vector; and A549 + RN + RANK:Fc (n = 10/group). RESULTS: In
      SCID mice who underwent subcutaneous A549 tumor cell injection, animals treated
      with A549 + RN had significantly smaller subcutaneous tumor size at 8 weeks. In
      an intratibial model of bony metastasis, animals injected with A549 cells
      developed a mixed lytic/blastic lesion with cortical destruction at 8 weeks.
      Treatment with RANK:Fc inhibited the formation of osteoclasts, led to a smaller
      tumor volume in bone, and inhibited the lytic component of the mixed lesion.
      Animals treated with A549 + RN had a decreased number of osteoblasts in bone
      lesions, smaller tumor volume, and inhibition of the blastic component of the
      mixed lesions. Combination treatment inhibited both the lytic and blastic
      components of the lesion. CONCLUSIONS: The NSCLC cell line A549 forms a mixed
      osteolytic/osteoblastic lesion in vivo. Noggin overexpression inhibited the
      formation of the osteoblastic aspect of the lesion in bone and the tumor growth
      in vivo. Treatment with RANK:Fc limited the formation of the lytic aspect of the
      mixed lesion and also inhibited the rate of in vivo tumor growth. Inhibition of
      both pathways is necessary to effectively inhibit the progression of mixed
      metastatic lesions in bone.

PMID- 16995813
TI  - Bone material properties in trabecular bone from human iliac crest biopsies after
      3- and 5-year treatment with risedronate.
AB  - Long-term effects of risedronate on bone mineral maturity/crystallinity and
      collagen cross-link ratio in triple iliac crest biopsies of osteoporotic women
      were evaluated. In this double-blinded study, 3- and 5-year treatment with
      risedronate arrested the tissue aging encountered in untreated osteoporosis and
      in osteoporosis treated with other antiresorptives. This effect may be
      contributing to risedronate's antifracture efficacy. INTRODUCTION: Risedronate is
      widely used in the treatment of osteoporosis. It reduces bone turnover, increases
      BMD, and decreases fracture risk. To date, there are no data available on the
      long-term effects of risedronate on bone material properties in humans. MATERIALS
      AND METHODS: Osteoporotic women enrolled in the VERT-NA trial received either
      risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects
      received calcium. They also received vitamin D supplementation if deficient at
      baseline. Triple iliac crest biopsies were collected from a subset of these
      subjects at baseline, 3 years, and 5 years. Mineral maturity/crystallinity and
      collagen cross-link ratio was measured in these biopsies using Fourier transform
      infrared imaging. RESULTS: Patients that received placebo exhibited increased
      mineral maturity/crystallinity and collagen cross-link ratio after 3 and 5 years
      compared with baseline values. On the contrary, patients that received
      risedronate retained baseline values in both bone material indices throughout. A
      more spatially detailed analysis revealed that this was achieved mainly through
      beneficial effects on active bone-forming areas. Surprisingly, patients that
      received risedronate achieved premenopausal values at bone-forming areas in both
      indices after 5 years of treatment. CONCLUSION: Long-term treatment with
      risedronate affects bone material properties (mineral maturity/crystallinity and
      collagen cross-link ratio) and arrests the tissue aging apparent in untreated
      osteoporosis. These changes at the material level of the bone matrix may
      contribute to risedronate's rapid and sustained antifracture efficacy in
      osteoporotic patients.

PMID- 16995814
TI  - Leptin inhibits bone formation not only in rodents, but also in sheep.
AB  - This study examines the effect of long-term ICV administration of leptin in ewes.
      We found that central application significantly decreased osteoblast activity as
      measured by serum analysis as well as by histomorphometry, resulting in decreased
      trabecular bone volume. These data provide additional evidence that bone
      formation and therefore bone remodeling is at least in part centrally controlled.
      INTRODUCTION: Genetic studies in mice have identified leptin as a potent
      inhibitor of bone formation acting through the central nervous system and
      unraveled the central nature of bone mass control and its disorders. Although
      these studies have radically enhanced our understanding of skeletal physiology
      because they have established a hypothalamic regulation of bone remodeling
      through the sympathetic nervous system, controversy remains about the
      physiological relevance of these observations because leptin's effect on bone
      after intracerebroventricular (ICV) application has only been shown in mice. To
      address whether leptin has a role in regulating bone mass beyond rodents, we
      treated ewes with long-term ICV application of leptin and analyzed the bone
      phenotype after a treatment period of 3 months. MATERIALS AND METHODS: Three
      groups of corriedale sheep were compared: (1) control entire (control), (2)
      ovariectomy (OVX) and ICV application of cerebrospinal fluid (CSF); and (iii) OVX
      and ICV application of leptin (leptin). Analysis included histomorphometric
      characterization of iliac crest, spine and femur by histology and biomechanical
      testing and measurement of bone turnover parameters in serum and urine. RESULTS:
      Central application of leptin decreased bone formation by 70% and mineralizing
      surface (MS/BS, 39.4 +/- 3.3% versus 16.1 +/- 2.1%) significantly (p < 0.01).
      Whereas OVX increased osteoclast indices and urinary cross-lap excretion by two
      and three times, respectively, serum parameters of osteoblast activity were
      significantly reduced by ICV application of leptin (p < 0.01). Consequently, ewes
      treated with leptin were osteopenic (iliac crest BV/TV entire, 22.7 +/- 1.3%;
      CSF, 18.9 +/- 2.4%; leptin, 12.4 +/- 2.6%), whereas bone torsional failure load
      reflecting the cortex of the tibia was not yet changed after 3 months of
      treatment (p < 0.01). CONCLUSIONS: Taken together, these data suggest that leptin
      controls bone formation after ICV application, leading to reduction of trabecular
      bone mass in sheep. Most importantly, however, they show that the central
      regulation of bone formation is not limited to rodents, but is also found in
      large animals, providing further evidence that bone remodeling in vertebrates is
      centrally controlled.

PMID- 16995815
TI  - Hypothalamic regulation of cortical bone mass: opposing activity of Y2 receptor
      and leptin pathways.
AB  - NeuropeptideY-, Y2 receptor (Y2)-, and leptin-deficient mice show similar
      anabolic action in cancellous bone but have not been assessed in cortical bone.
      Cortical bone mass is elevated in Y2(-/-) mice through greater osteoblast
      activity. In contrast, leptin deficiency results in reduced bone mass. We show
      opposing central regulation of cortical bone. INTRODUCTION: Treatment of
      osteoporosis is confounded by a lack of agents capable of stimulating the
      formation of bone by osteoblasts. Recently, the brain has been identified as a
      potent anabolic regulator of bone formation. Hypothalamic leptin or Y2 receptor
      signaling are known to regulate osteoblast activity in cancellous bone. However,
      assessment of these pathways in the structural cortical bone is critical to
      understanding their role in skeletal health and their potential clinical
      relevance to osteoporosis and its treatment. MATERIALS AND METHODS: Long bones of
      16-week male ob/ob and germline and hypothalamic Y2(-/-) mice were assessed by
      QCT. Cortical osteoblast activity was assessed histologically. RESULTS: The
      femora of skeletally mature Y2(-/-) mice and of leptin-deficient ob/ob and Y2(-/
      )ob/ob mice were assessed for changes in cortical osteoblast activity and bone
      mass. Ablation of Y2 receptors increased osteoblast activity on both endosteal
      and periosteal surfaces, independent of leptin, resulting in increased cortical
      bone mass and density in Y2(-/-) mice along the entire femur. Importantly, these
      changes were evident after deletion of hypothalamic Y2 receptors in adult mice,
      with a 5-fold elevation in periosteal bone formation. This is in marked contrast
      to leptin-deficient models that displayed reduced cortical mass and density.
      These changes were associated with substantial differences in calculated strength
      between the Y2(-/-) and leptin-deficient mice. CONCLUSIONS: These results
      indicate that the Y2-mediated anabolic pathway stimulates cortical and cancellous
      bone formation, whereas the leptin-mediated pathway has opposing effects in
      cortical and cancellous bone, diminishing the production of cortical bone. The
      findings from conditional hypothalamic Y2 knockout show a novel, inducible
      control mechanism for cortical bone formation and a potential new pathway for
      anabolic treatment of osteoporosis.

PMID- 16995816
TI  - Quantification of the roles of trabecular microarchitecture and trabecular type
      in determining the elastic modulus of human trabecular bone.
AB  - The roles of microarchitecture and types of trabeculae in determining elastic
      modulus of trabecular bone have been studied in microCT images of 29 trabecular
      bone samples by comparing their Young's moduli calculated by finite element
      analysis (FEA) with different trabecular type-specific reconstructions. The
      results suggest that trabecular plates play an essential role in determining
      elastic properties of trabecular bone. INTRODUCTION: Osteoporosis is an age
      related disease characterized by low bone mass and architectural deterioration.
      Other than bone volume fraction (BV/TV), microarchitecture of bone is also
      believed to be important in governing mechanical properties of trabecular bone.
      We quantitatively examined the role of microarchitecture and relative
      contribution of trabecular types of individual trabecula in determining the
      elastic property of trabecular bone. MATERIALS AND METHODS: Twenty-nine human
      cadaveric trabecular bone samples were scanned at 21-mum resolution using a
      microCT system. Digital topological analysis (DTA) consisting of skeletonization
      and classification was combined with a trabecular type-specific reconstruction
      technique to extract the skeleton and identify topological type of trabeculae of
      the original trabecular bone image. Four different microCT-based finite element
      (FE) models were constructed for each specimen: (1) original full voxel; (2)
      skeletal voxel; (3) rod-reconstructed, preserving rod volume and plate skeleton;
      and (4) plate-reconstructed, preserving plate volume and rod skeleton. For each
      model, the elastic moduli were calculated under compression along each of three
      image-coordinate axis directions. Plate and rod tissue fractions directly
      measured from DTA-based topological classification were correlated with the
      elastic moduli computed from full voxel model. RESULTS: The elastic moduli of
      skeleton models were significantly correlated with those of full voxel models
      along all three coordinate axes (r(2) = 0.38 approximately 0.53). The rod
      reconstructed model contained 21.3% of original bone mass and restored 1.5% of
      elastic moduli, whereas the plate-reconstructed model contained 90.3% of bone
      mass and restored 53.2% of elastic moduli. Plate tissue fraction showed a
      significantly positive correlation (r(2) = 0.49) with elastic modulus by a power
      law, whereas rod tissue fraction showed a significantly negative correlation
      (r(2) = 0.42). CONCLUSIONS: These results quantitatively show that the
      microarchitecture alone affects elastic moduli of trabecular bone and trabecular
      plates make a far greater contribution than rods to the bone's elastic behavior.

PMID- 16995817
TI  - Vitamin D action and regulation of bone remodeling: suppression of
      osteoclastogenesis by the mature osteoblast.
AB  - Vitamin D acts through the immature osteoblast to stimulate osteoclastogenesis.
      Transgenic elevation of VDR in mature osteoblasts was found to inhibit
      osteoclastogenesis associated with an altered OPG response. This inhibition was
      confined to cancellous bone. This study indicates that vitamin D-mediated
      osteoclastogenesis is regulated locally by OPG production in the mature
      osteoblast. INTRODUCTION: Vitamin D stimulates osteoclastogenesis acting through
      its nuclear receptor (VDR) in immature osteoblast/stromal cells. This
      mobilization of calcium stores does not occur in a random manner, with bone
      preferentially removed from cancellous bone. The process whereby the systemic,
      humoral regulator is targeted to a particular region of the skeleton is unclear.
      MATERIALS AND METHODS: Bone resorption was assessed in mice with vitamin D
      receptor transgenically elevated in mature osteoblasts (OSVDR). Vitamin D
      mediated osteoclastogenesis was examined in vitro using OSVDR osteoblasts and
      osteoblastic RANKL: osteoprotegerin (OPG) examined in vivo and in vitro after
      vitamin D treatment. RESULTS: Vitamin D-mediated osteoclastogenesis was reduced
      in OSVDR mice on chow and calcium-restricted diets, with effects confined to
      cancellous bone. OSVDR osteoblasts had a reduced capacity to support
      osteoclastogenesis in culture. The vitamin D-mediated reduction in OPG expression
      was reduced in OSVDR osteoblasts in vivo and in vitro, resulting in a reduced
      RANKL/OPG ratio in OSVDR compared with wildtype, after exposure to vitamin D.
      CONCLUSIONS: Mature osteoblasts play an inhibitory role in bone resorption, with
      active vitamin D metabolites acting through the VDR to increase OPG. This
      inhibition is less active in cancellous bone, effectively targeting this region
      for resorption after the systemic release of activated vitamin D metabolites.

PMID- 16995818
TI  - Bone sialoprotein enhances migration of bone marrow stromal cells through
      matrices by bridging MMP-2 to alpha(v)beta3-integrin.
AB  - BMSCs migrate through matrix barriers and differentiate into osteoblasts. BSP
      enhances osteogenic cell migration through basement membrane and collagen
      matrices in vitro by localizing MMP-2 on the cell surface through alpha(v)beta(3)
      integrin. INTRODUCTION: The specific mechanisms by which bone marrow stromal
      cells (BMSCs) leave their primary sites, move through matrices encountered during
      homing to their site of final differentiation, and remove preexisting matrices in
      preparation for bone matrix production are not well understood. MATERIALS AND
      METHODS: The enhanced migration of human osteoblast precursor cells through
      matrix barriers by bone sialoprotein (BSP) was studied by a modified Boyden
      chamber assay. The bridging of normally soluble matrix metalloproteinase 2 (MMP
      2) to the cell surface receptor, alpha(v)beta(3)-integrin, by BSP was analyzed by
      flow cytometry. RESULTS: BSP enhanced the in vitro passage of BMSCs and pre
      osteoblasts through matrix barriers (Matrigel and denatured type I collagen) in a
      dose-dependent manner. An intact ArgGlyAsp (RGD) was required in the BSP for
      enhanced migration through the barriers but was not sufficient, as shown by the
      inactivity of two other SIBLING (Small Integrin-Binding LIgand, N-linked
      Glycoprotein) family members, osteopontin and dentin matrix protein-1. The
      specificity of the BSP enhancement activity was apparently caused by this
      molecule's ability to bridge MMP-2 to the cell surfaces. CONCLUSIONS: Pre
      osteoblasts and their BMSC precursors may use MMP-2/BSP/integrin complexes to
      disrupt matrix barriers during migration to their final destinations in vivo.

PMID- 16995819
TI  - Regulation of growth plate chondrocytes by 1,25-dihydroxyvitamin D3 requires
      caveolae and caveolin-1.
AB  - We examined the role of caveolae and caveolin-1 in the mechanism of
      1alpha,25(OH)(2)D(3) action in growth plate chondrocytes. We found that caveolae
      are required for rapid 1alpha,25(OH)(2)D(3)-dependent PKC signaling, and caveolin
      1 must be present based on studies using chondrocytes from Cav-1(-/-) mice.
      INTRODUCTION: 1,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] regulates
      endochondral ossification in part through membrane-associated mechanisms,
      including protein kinase C (PKC) signaling activated by a membrane-associated
      1alpha,25(OH)(2)D(3)-binding protein, ERp60. We tested the hypothesis that
      caveolae are required for 1alpha,25(OH)(2)D(3) action and play an important role
      in regulating chondrocyte biology and growth plate physiology. MATERIALS AND
      METHODS: Rat costochondral chondrocytes were examined for caveolae by
      transmission electron microscopy of cultured cells and of cells in situ. Western
      blots and confocal microscopy were used to detect caveolae proteins including
      caveolin-1 (Cav-1) and 1alpha,25(OH)(2)D(3) receptors. Caveolae cholesterol was
      depleted with beta-cyclodextrin (CD) and effects of 1alpha,25(OH)(2)D(3) on PKC,
      DNA synthesis, alkaline phosphatase, and proteoglycan production determined.
      Chondrocytes from Cav-1(-/-) and C57BL/6 wildtype mice were also treated with
      1alpha,25(OH)(2)D(3). Epiphyses and costochondral junctions of 8-week-old male
      Cav-1(-/-) and wildtype mice (N = 8) were compared by histomorphometry and
      microCT. Data were analyzed by ANOVA and Bonferroni for posthoc comparisons.
      RESULTS: Growth zone chondrocytes had caveolae and Cav-1, -2, and -3. Resting
      zone chondrocytes, which do not exhibit a rapid 1alpha,25(OH)(2)D(3)-dependent
      increase in PKC activity, also had these caveolins, but caveolae were larger and
      fewer in number. ERp60 but not VDR co-localized with Cav-1 in plasma membranes
      and in lipid rafts. CD-treatment blocked 1alpha,25(OH)(2)D(3) effects on all
      parameters tested. The Cav-1(-/-) cells did not respond to 1alpha,25(OH)(2)D(3),
      although 1alpha,25(OH)(2)D(3) increased PKC, alkaline phosphatase, and [(35)S]
      sulfate incorporation in wildtype C57BL/6 cells. Histology and microCT showed
      that Cav-1(-/-) growth plates were longer and had more hypertrophic cells in each
      column. Growth plate changes were reflected in the metaphysis. CONCLUSIONS: The
      membrane-mediated effects of 1alpha,25(OH)(2)D(3) require caveolae and Cav-1, and
      Cav-1 deficiency results in altered growth plate physiology.

PMID- 16995820
TI  - Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts
      through the MAPK signaling pathway.
AB  - Our study indicates that recombinant adiponectin induced RANKL and inhibited OPG
      expression in human osteoblasts through the AdipoR1/p38 MAPK pathway, and these
      responses contributed to the adiponectin-induced osteoclasts formation in the co
      culture of osteoblast and peripheral blood monocytes systems. These findings
      showed that adiponectin increased osteoclast formation indirectly through
      stimulating RANKL and inhibiting OPG production in osteoblasts. It also suggests
      the pharmacological nature of recombinant adiponectin that indirectly induces
      osteoclasts formation. INTRODUCTION: Recently, adiponectin has emerged as an
      element in the regulation of bone metabolism, but the mechanism remains. This
      study was undertaken to investigate the action of adiponectin on
      osteoclastogenesis through revealing RANKL and osteoprotegerin (OPG) expression
      in osteoblasts and osteoclast formation. MATERIALS AND METHODS: Real-time
      quantitative PCR and ELISA were used to detect RANKL and OPG mRNA and protein
      expression in cultured human osteoblasts. The involved signal pathway was studied
      using mitogen-activated protein kinase (MAPK) inhibitor and adiponectin receptor
      1 (AdipoR1) siRNA. The effects of recombinant adiponectin on osteoclasts
      formation also were examined in the co-culture systems of osteoblast and
      peripheral blood monocytes (PBMCs) systems or purified CD14 + PBMCs cultures.
      RESULTS: Our study showed that recombinant adiponectin induced RANKL and
      inhibited OPG mRNA expression in human osteoblasts in a dose- and time-dependent
      manner. Adiponectin also increased soluble RANKL and decreased OPG secretion in
      osteoblasts conditioned media. Suppression of AdipoR1 with siRNA abolished the
      adiponectin-regulated RANKL and OPG mRNA expression in osteoblasts. Furthermore,
      pretreatment of osteoblasts with the MAPK inhibitor SB203580 abolished
      adiponectin-regulated RANKL and OPG mRNA expression. Adiponectin induced
      osteoclast formation in the co-culture systems of osteoblast and PBMCs systems,
      and OPG entirely blocked this response. However, adiponectin had no direct effect
      on the differentiation of osteoclast precursor purified CD14 + PBMCs.
      CONCLUSIONS: These data indicate that recombinant adiponectin induced RANKL and
      inhibited OPG expression in human osteoblasts through the AdipoR1/p38 MAPK
      pathway, and these responses contributed to the adiponectin-induced osteoclast
      formation in the co-culture of osteoblast and PBMCs systems. These findings
      showed that adiponectin increased osteoclast formation indirectly through
      stimulating RANKL and inhibiting OPG production in osteoblasts. It suggests the
      pharmacological nature of recombinant adiponectin that indirectly induces
      osteoclasts formation.

PMID- 16995821
TI  - Alpha9beta1: a novel osteoclast integrin that regulates osteoclast formation and
      function.
AB  - We identified a previously unknown integrin, alpha(9)beta(1), on OCLs and their
      precursors. Antibody to alpha(9) inhibited OCL formation in human marrow
      cultures, and OCLs from alpha(9) knockout mice had a defect in actin ring
      reorganization and an impaired bone resorption capacity. INTRODUCTION: Integrins
      play important roles in osteoclast (OCL) formation and function. Mature OCLs
      mainly express alpha(v)beta(3) integrin, a heterodimer adhesion receptor that has
      been implicated in osteoclastic bone resorption. We identified ADAM8, a
      disintegrin and metalloproteinase, as a novel stimulator of OCL differentiation
      and showed that the disintegrin domain of ADAM8 mediated its effects on OCL
      formation. Because the disintegrin domain of ADAM8 does not bind Arg-Gly-Asp
      (RGD) sequences, we determined which integrin bound ADAM8 and characterized its
      role in OCL formation and activity. MATERIALS AND METHODS: Chinese hamster ovary
      cells (CHO) expressing different integrin subunits were tested for their capacity
      to bind the disintegrin domain of ADAM8. Mouse or human bone marrow cells and
      purified OCL precursors were tested for alpha(9)beta(1) integrin expression by
      Western blot, immunocytochemistry, and real-time RT-PCR. A monoclonal antibody to
      human alpha(9) was used to block alpha(9)beta(1) on OCL precursors stimulated by
      1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] or RANKL. Vertebrae of 7
      day-old alpha(9)(-/-) mice and wildtype (WT) littermates were compared using bone
      histomorphometry and 3D microCT analysis. RESULTS: Alpha(9) integrin was
      expressed by mouse and human bone marrow-derived OCLs and their precursors.
      Importantly, the anti-alpha(9) antibody inhibited human OCL formation stimulated
      by 1alpha,25(OH)(2)D(3) or RANKL dose-dependently. Furthermore, analysis of OCLs
      formed in marrow cultures from alpha(9)(-/-) mice showed that the OCLs formed
      were more contracted and formed significantly less bone resorption pits on dentin
      slices. Histologic analysis of alpha(9)(-/-) vertebrae showed thickened
      trabecular regions and retained cartilage within vertebral bodies of alpha(9)(-/
      ) mice. 3D microCT analysis of alpha(9)(-/-) vertebrae also showed a significant
      increase in trabecular bone volume/total tissue volume and a tendency for
      decreased trabecular separation compared with WT mice. CONCLUSIONS: These results
      support a previously unknown role for alpha(9)beta(1) integrin in OCL formation
      and function.

PMID- 16995822
TI  - Surveillance for early detection of aggressive parathyroid disease: carcinoma and
      atypical adenoma in familial isolated hyperparathyroidism associated with a
      germline HRPT2 mutation.
AB  - Familial hyperparathyroid syndromes involving mutations of HRPT2 (also CDC73), a
      tumor suppressor, are important to identify because the relatively high incidence
      of parathyroid malignancy associated with such mutations warrants a specific
      surveillance strategy. However, there is a dearth of reports describing
      experience with surveillance and early detection informed by genetic insight into
      this disorder. INTRODUCTION: Familial isolated hyperparathyroidism (FIHP) is a
      rare cause of parathyroid (PT) tumors without other neoplasms or
      endocrinopathies. Germline mutations in CASR, MEN1, and rarely, HRPT2 have been
      identified in kindreds with FIHP. HRPT2 mutations may be enriched in FIHP
      families with PT carcinoma, underscoring the importance of identifying causative
      mutations. MATERIALS AND METHODS: A 13-year-old boy, whose father had died of PT
      carcinoma, developed primary hyperparathyroidism. A left superior PT mass was
      identified by ultrasonography and removed surgically. Aggressive histological
      features of the boy's tumor included fibrous trabeculae, mitoses, and microscopic
      capsular infiltration. Two years later, under close biochemical surveillance,
      primary hyperparathyroidism recurred 5 months after documentation of
      normocalcemia and normal parathyroid status. Ultrasound and MRI identified a
      newly enlarged right superior PT gland but indicated no recurrent disease in the
      left neck. Histologic features typical of a benign adenoma were evident after
      surgical extirpation of the gland. RESULTS: Leukocyte DNA analysis revealed a
      frameshift mutation in exon 2 of HRPT2. The initial tumor manifested the expected
      germline HRPT2 mutation, plus a distinct somatic frameshift mutation, consistent
      with the Knudson "two hit" concept of biallelic inactivation of a classic tumor
      suppressor gene. Genetic screening of the patient's 7 asymptomatic and previously
      normocalcemic siblings revealed three with the same germline HRPT2 mutation. One
      of the siblings newly identified as mutation-positive was noted to be
      hypercalcemic at the time of the genetic screening. He was found to have a PT
      adenoma with aggressive features. Two of the five children of another mutation
      positive sibling also carry the same HRPT2 mutation. CONCLUSIONS: Despite the
      reported rarity of HRPT2 mutations in FIHP, a personal or family history of PT
      carcinoma in FIHP mandates serious consideration of germline HRPT2 mutation
      status. This information can be used in diagnostic and management considerations,
      leading to early detection and removal of potentially malignant parathyroid
      tumors.

PMID- 16995823
TI  - Abstracts from the 77th Annual Meeting of the American Thyroid Association,
      Phoenix, Arizona, USA, October 11-15, 2006.

PMID- 16995830
TI  - Cognitive functioning in school-aged children with vertically acquired HIV
      infection being treated with highly active antiretroviral therapy (HAART).
AB  - In today's era of highly active antiretroviral therapy (HAART), few children with
      HIV-1 infection experience severe central nervous system (CNS) manifestations
      indicative of encephalopathy. However, little is known about the neurocognitive
      strengths and weaknesses of HIV-infected children treated with HAART. This cross
      sectional study is the first to systematically investigate the relation between
      cognitive functioning and medical markers in HIV-infected children and
      adolescents treated with HAART with varying levels of computed tomography (CT)
      brain scan abnormalities. The Wechsler Intelligence Scale for Children-Third
      Edition was administered to 41 vertically infected children (mean age = 11.2
      years) treated with HAART for at least 1 year. Other procedures at the time of
      testing included CT brain scans and collection of CD4 cell counts and plasma HIV1
      RNA PCR. Although global cognitive functioning among participants was in the
      Average range, children with minimal to moderate CT brain scan abnormalities
      scored significantly lower than children with normal scans on composite measures
      of cognitive functioning and five specific subtests, especially tasks involving
      executive functions. Furthermore, children with worse immune status (CD4+ counts
      < or = 500) scored lower on subtests measuring processing speed. Viral load was
      unrelated to cognitive test scores. Thus, children with HIV being treated with
      HAART remain at risk for developing CNS disease. Findings emphasize the
      importance of conducting neuropsychological assessments in this population,
      particularly for children with cortical atrophy and absolute CD4+ cell counts <
      or = 500.

PMID- 16995831
TI  - Conduct problems in adolescence: three domains of inhibition and effect of
      gender.
AB  - Behavioral and neuropsychological evidence has often shown that children with
      conduct disorder drawn from clinical populations show problems with impulsivity
      and are impaired in motor tasks of inhibitory control. We explored the relation
      between conduct problems and inhibitory deficits in a community sample. Three
      domains of inhibition were explored in 54 adolescents with conduct problems
      compared to 53 age, IQ, sex, school, and ethnicity matched controls in 2
      geographical areas. Motor response inhibition was assessed using the Stop task,
      verbal inhibition using the Hayling Sentence Completion test, and cognitive
      interference inhibition using the Stroop task. Adolescents with conduct problems
      showed deficits in executive and inhibitory processes of the motor response
      inhibition task, but were unimpaired in cognitive or verbal inhibitory control.
      No sex differences were observed and impairments were independent of IQ or
      geographical location. Findings suggest that motor deficits, rather than higher
      cognitive forms of inhibitory control, are a specific deficit in children with
      conduct problems, that girls are as affected as boys, and that motor
      impulsiveness is a dimensional trait associated with conduct problems, as it is
      also observed in the community.

PMID- 16995832
TI  - Age-related differences in performance of phonemic verbal fluency measured by
      Controlled Oral Word Association Task (COWAT): a meta-analytic study.
AB  - Meta-analytical procedures were used to examine the research findings on age
      related changes in phonemic verbal fluency measured by the Controlled Oral Word
      Association Task (COWAT). Data from 26 studies comparing adults from different
      age ranges were analyzed. An effect of aging was found in almost all age
      comparisons especially after 40 years of age. Results revealed a decline of this
      verbal ability after 60 years, which accelerates through the late 80s. Gender may
      influence COWAT performance after the sixth decade, favoring women over men.
      These results may be important in clinical situations where COWAT is used to
      assert pathological changes.

PMID- 16995833
TI  - A comparison of the reach-to-grasp movement between children and adults: a
      kinematic study.
AB  - In this study, the reach-to-grasp movement of 5-year-old children was compared to
      that of adults. Participants were required to reach out and grasp objects, with
      and without on-line visual feedback. Object size and distance were covaried in a
      within-subjects design and it was found that for both groups, grip formation and
      reach kinematics were affected by the manipulation of either variable. Although
      there are a large number of similarities, a few differences between the two
      groups emerge. For the reaching component, the children revealed a longer
      movement duration and deceleration time and a lower maximum height of wrist
      trajectory than in adults. For the grasp component, the children, in both the
      vision and no-vision condition, show a maximal finger aperture larger than the
      adults. Further, the children of this study were able to scale their grip
      aperture according to object size when visual feedback during the movement was
      lacking. These findings suggest that children adopt different strategies than
      adults when planning a reach-to-grasp movement on the basis of object size,
      distance, and the predictability of visual feedback. The results are discussed in
      terms of the neural mechanisms underlying hand action and how these mechanisms
      may not be fully developed by the age of 5.

PMID- 16995834
TI  - Source and item memory for odors and objects in children and young adults.
AB  - Recall and recognition memory for odors are poorer in children than in
      adolescents. In addition, children perform worse than young adults on source
      memory tasks using visual and auditory stimuli. However, source memory for odor
      stimuli has not been examined in children. This study investigated source and
      item memory for odors and objects in children (7-10 years old) and young adults
      (18-24 years old). During the study phase, 1 male and 1 female experimenter
      (sources) randomly presented either 16 odors or 16 objects to the participant.
      Presentation alternated between sources so that each source presented 8 stimuli.
      Once the 16 stimuli were presented, the sources exited and a third experimenter
      began the test phase. To assess item recognition memory, a stimulus from the
      study phase and a novel stimulus were presented to the participant who was asked
      to choose the stimulus presented during the study phase. Source memory was
      assessed with the 8 stimuli from the study phase not used in the item memory
      task. The experimenter presented a stimulus and asked whether the male or female
      experimenter had presented the stimulus during the study phase. Results indicate
      that difference scores between item and source memory for odors were
      significantly larger for children than for young adults, indicating poorer source
      memory for children than adults. Difference scores for objects did not
      distinguish between groups. It has been suggested that the frontal lobes play a
      critical role in source memory and odor memory--a brain region that continues to
      develop into adolescence. Poor performance among children on the source memory
      task for odors may be due in part to immaturity of the frontal lobes.

PMID- 16995835
TI  - Developmental changes in visual line bisection in women throughout adulthood.
AB  - It has been suggested that some hemispheric asymmetries change in a systematic
      way from young adulthood to older age. However, little is known whether these
      changes are due to differential aging of a single hemisphere or based on age
      related alterations of interhemispheric interactions. A sample of 281 right
      handed neurologically healthy participants (151 women), ranging from age 20 to
      79, was investigated with a line-bisection task. Previous studies indicate the
      midpoint estimation shows a consistent leftward bias from the veridical center,
      which is accentuated when the left hand is used to bisect lines. These findings
      support the view of a right hemispheric superiority in spatial attention. This
      study revealed this pattern to be stable in men throughout adulthood. However,
      women from 50 to 69 years of age showed a reduced leftward bias and a reduced
      hand effect compared to men and younger women. The results suggest that
      developmental changes in hemispheric asymmetry of spatial attention are more
      pronounced in women and support the view that neuromorphological changes during
      adulthood differ between sexes.

PMID- 16995837
TI  - Detection of heterozygous nonsense mutations in genes of interest using an
      Escherichia coli-based stop codon assay.
AB  - Since nonsense mutations are closely associated with severe conditions of genetic
      disorders, including familial cancers, rapid and precise detection of those
      mutations is very important for research purposes and molecular diagnosis.
      Currently, screening methods such as the FASAY (functional analysis of separated
      alleles in yeast) and the Y-SC (stop codon assay in yeast) are used for
      functional detection of nonsense mutations in genes of interest. But these yeast
      based approaches are time-consuming, expensive and complicated. In order to
      circumvent these problems, we, in the present study, devised a novel Escherichia
      coli-based screening method, the E-SC (E. coli stop codon assay) for the
      detection of heterozygous nonsense mutations in genes of interest. Our strategy
      was based on the fact that the plasmid replicating with a low copy number in E.
      coli allows an effective separation of normal and mutant alleles. Moreover, it
      relies on the expression vector, resulting in the formation of white and blue
      colonies for mutant and normal alleles through the expression of PCR-amplified
      fragment/lacZ fusion protein respectively. To evaluate the applicability of the E
      SC method for the detection of the heterozygous truncating mutation, PCR
      amplified exon 7 of the StAR [steroidogenic acute regulatory protein; causative
      gene of the CAH (congenital lipoid adrenal hyperplasia)] and RT (reverse
      transcription)-PCR-amplified full-length cDNA of MeCP2 (methyl-CpG-binding
      protein 2; causative gene of Rett syndrome) were used. The E-SC showed an almost
      1:1 ratio of blue/white colonies in all patients examined, whereas the control
      samples produced blue colonies only. These results demonstrate that the E-SC
      system is useful for rapid and precise detection of known and unknown
      heterozygous truncation mutations in genes that cause genetic disorders and
      familial cancers.

PMID- 16995840
TI  - Creatine kinase activity in patients with diabetes mellitus type I and type II.
AB  - Diabetes mellitus can be looked upon as an array of diseases, all of which
      exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes
      mellitus) is well understood, the same is not true for diabetes mellitus type II.
      In the latter case, relative contribution of the two factors (insulin resistance
      or decreased insulin secretion) varies individually, being highly increased in
      peripheral tissues and strictly dependant on insulin for glucose uptake.
      Moreover, in patients with diabetes mellitus type II, disbalance at the level of
      regulation of glucose metabolism as well as lipid metabolism has been noted in
      skeletal muscles. It is normal to assume that in this type of diabetes, these
      changes are reflected at the level of total activity of enzyme creatine kinase.
      This experimental work was performed on a group of 80 regular patients of
      Sarajevo General Hospital. Forty of those patients were classified as patients
      with diabetes type I and forty as patients with diabetes type II. Each group of
      patients was carefully chosen and constituted of equal number of males and
      females. The same was applied for adequate controls. Concentration of glucose was
      determined for each patient with GOD method, while activity of creatine kinase
      was determined with CK-NAC activated kit. Statistical analysis of the results was
      performed with SPSS software for Windows. Obtained results point out highly
      expressed differences in enzyme activity between two populations examined.
      Changes in enzyme activity are more expressed in patients with diabetes type II.
      Positive correlation between concentration of glucose and serum activity of the
      enzyme is seen in both categories of diabetic patients which is not the case for
      the patients in control group. At the same time, correlation between age and type
      of diabetes does exist . This is not followed at the level of enzyme activity or
      concentration of glucose.

PMID- 16995838
TI  - Clustering of monosialyl-Gb5 initiates downstream signalling events leading to
      invasion of MCF-7 breast cancer cells.
AB  - Invasion is a complex process controlled by secretion and activation of
      proteases, alteration of integrin levels and GSL (glycosphingolipid) patterns.
      Differential organization of GSLs with specific membrane proteins and signal
      transducers in GEMs (GSL-enriched microdomains), initiates signalling events to
      modify cellular phenotype. Although the GSL monosialyl-Gb5 has been linked with
      invasion, its functional role in invasion is poorly described and understood. To
      investigate this problem, we induced the invasion of human breast cancer cells
      and subsequently explored the underlying mechanism. In the present study, the
      invasion of human MCF-7 breast cancer cells is highly dependent on clustering of
      monosialyl-Gb5, and the subsequent activation of monosialyl-Gb5-associated focal
      adhesion kinase and cSrc in GEM leading to the downstream activation of
      extracellular-signal-regulated kinase (ERK). As a result, we observed increased
      expression levels and activity of matrix metalloproteinases-2 and -9, which
      correlated with decreased expression of integrins alpha1 and beta1. Together
      these results suggest that the organization of crucial molecules in GEMs of MCF-7
      cells is critical for their invasive properties.

PMID- 16995841
TI  - Photoperiodism as a modifier of effect of extremely low-frequency electromagnetic
      field on morphological properties of pineal gland.
AB  - The aim of our study was to determine, using histological and stereological
      methods, whether photoperiodism has any impact on the effects that chronic (three
      month long) exposure to LF-EMF (50Hz) has on morphological characteristics on
      rat's pineal gland. The experiment was performed on 48 Mill Hill male rats (24
      experimental and 24 control). Upon birth, 24 rats were exposed for 7h a day, 5
      days a week for 3 months to LF-EMF (50 Hz, 50-500microT, 10V/m). In the winter
      (short days, long nights), the activity of the pineal gland and neuroendocrine
      sensitivity is increased. The study was performed both during summer and winter,
      following the identical protocol. After sacrifice of animals, samples of pineal
      gland were processed for HE staining and then were analyzed using the methods of
      stereology. The most significant changes in epiphysis in the first group of
      animals in wintertime are: altered glandular feature, hyperemia, reduced
      pinealocytes with pale pink, poor cytoplasm and irregular, stick-form nuclei. In
      the second group (II) pinealocytes are enlarged, with vacuolated cytoplasm and
      hyper chromatic, enlarged nucleus. Morphological changes of pineal gland at rats
      in the summertime were not as intense as in the winter and finding of the gland
      in the group II is compatible with those from the control group. Stereological
      results show both in winter and summer in the first group the decrease of volume
      density of pinealocytes, their cytoplasm and nuclei and in the second group in
      winter increase the volume density of pinealocytes, cytoplasm and nuclei, while
      in the second group the results in summertime are equal to those from the control
      group. Photoperiodism is modifier of effect of LF-EMF on morphological structure
      of pineal gland, because the gland recovery is incomplete in winter and
      reversible in summer.

PMID- 16995842
TI  - Five-year survival-after first-ever stroke.
AB  - The aim of the study was to analyze the 5-year survival after first-ever ischemic
      stroke and intracerebral hemorrhage. In this study 836 patients were analyzed
      with a first-ever stroke admitted at the Department of Neurology Tuzla, Bosnia
      and Herzegovina, from January 1(st) 1997 to December 31(st) 1998. Of these 613
      (73,3%) were ischemic strokes and 223 intracerebral hemorrhages (26,7%)
      Subarachnoid hemorrhages were excluded. After hospitalization surviving patients
      examined periodically, and a final examination was performed 5 years after the
      stroke. Overall, case-fatility at the first month was 36% (301/836) and the
      mortality rate was significantly higher in the patients with intracerebral
      hemorrhage (58,3% vs. 27,9%, p<0,0001). The first year survived 60% patients with
      ischemic stroke, and 38% with intracerebral hemorrhage. After 5 years, 188 (31%)
      patients with ischemic stroke and 53 (24%) with intracerebral hemorrhage were
      alive (p=0,5), and the cumulative survival rate for the entire study was 29%.
      Among 30-day survivors (n=535) surviving rate after 5 years was significantly
      higher in patients with intracerebral hemorrhage (57% vs. 42,5%, p=0,01). The
      survival rate was the highest for those 50 years and younger (57%), and the
      lowest for those aged over 70 years (9%). Predictors of 5-year mortality were
      older age and hypertension for both types of stroke, heart diseases for ischemic
      stroke and diabetes for intracerebral hemorrhage. Long-term survival after first
      ever ischemic stroke and intracerebral hemorrhage is similar. However, among 30
      day survivors the 5-year survival is better in patients with intracerebral
      hemorrhage.

PMID- 16995843
TI  - Sensory-motor index is useful parameter in electroneurographical diagnosis of
      carpal tunnel syndrome.
AB  - It was performed electroneurographic (ENG) studies with surface electrodes and
      examined nervus medianus (NM) in 60 patients (38 females), average age of 50,28
      years (X+/-SD=50,28+/-11), with clinical diagnosis of carpal tunnel syndrome
      (CTS) and at least one border or discrete abnormal value of conventional
      electrophysiological tests. It was also examined 57 healthy individuals (33
      females) as control group, average age of 45,65 years (X+/-SD=45,65+/-9,68). The
      sensitivity and specificity of sensory-motor index (SMI), terminal latency index
      (TLI) and residual latency (RL) were calculated and compared. SMI is determinate
      by using following formula: distal distance (DD) (in cm)/distal motor latency
      (DML) (in ms) + sensory conduction velocity (SCV) (in m/s)/motor conduction
      velocity (MCV) (in m/s) of NM. SCV of NM was measured by antidromic technique in
      segment wrist-index finger and MCV of NM in forearm segment above wrist. SMI mean
      value of control group was 3,45 (X+/-SD=3,45+/-0,45) with lower limit of normal
      value 2,82 and in patients with CTS 2,13 (X+/-SD=2,13 +/-0,37). The sensitivity
      of SMI in patients with CTS was 98,51%. SMI is useful parameter in
      electroneurographical diagnosis of CTS and it's determination is easy and fast
      and specially important in cases with border or discrete abnormal values of other
      NM electrophysiological parameters, when SMI values can indicate incipient phase
      of CTS evolution. In rare cases (about 1%) of CTS with selective NM motor axons
      affection, SMI may have normal value (false negative result), but DML is always
      prolonged in this cases. SMI is not dependent on age and DD values in patients
      with CTS and control subjects.

PMID- 16995844
TI  - The dry plant extract of common bean seed (Phaseoli vulgari pericarpium) does not
      have an affect on postprandial glycemia in healthy human subject.
AB  - The aim of present study was to assess the effects and safety of a dry Phaseoli
      vulgari pericarpium (PVP) extract on postprandial glycemia in healthy
      participants. A randomized crossover experiment where participants received
      either PVP extract or placebo. Chemical compounds in dry extract were assessed by
      established methods. Eighteen healthy participants (9 male and 9 female) aged
      29+/-4,8 years, body mass index (BMI) 23+/-3,7 kg/m(2) were recruited among
      students and staff at the Faculty of Pharmacy, University of Belgrade. All
      participants were able to follow the study protocol without difficulty. The
      participants received either PVP extract or placebo 30 minutes before a 50g oral
      glucose tolerance test (OGTT). The protocol followed the guidelines for the OGTT
      with blood samples drawn at 0, 15, 30, 60, 90 and 120 min. This study
      demonstrated that there was no significantly effect of the PVP extract on
      incremental blood glucose (IBG) and their areas under the curve (AUC) neither
      male nor female participants. However, IBG together with AUC changes were
      significantly lower in male compared with female participants in treated and
      untreated groups. The presence of chrome, soluble fiber, vitamin C, protein,
      glucose and lectins were also quantified. The applied amount of PVP extract was
      unable to produce the postprandial hypoglycemia. We assumed that amounts of
      chrome, soluble fiber, vitamin C which have beneficial effects on diabetes
      treatment were sufficient to produce hypoglycemia.

PMID- 16995845
TI  - A case of T/null anaplastic large cell lymphoma arising in lung.
AB  - Anaplastic large cell lymphoma (ALCL) is a rare non-Hodgkin, T-cell lymphoma,
      representing only 2-3% of all lymphoid neoplasm's in adults according to World
      Health Organization (WHO). CD30 antigen-positive, large neoplastic cells
      characterize ALCL. We present here a 46-year-old male with pulmonary ALCL
      previously diagnosed with Hodgkin disease. Microscopically, atypical bi-and
      multinucleated cells with frequent mitoses were present. The neoplastic cells
      were large and had clear cytoplasm, large vesicular nuclei, and prominent
      nucleoli. Immunophenotypic analysis revealed LCA, vimentin and CD30 positivity.
      ALK immunostaining was negative. Immunohistochemical profile was consistent with
      ALK negative ALCL. The progression of Hodgkin lymphoma to aggressive non-Hodgkin
      lymphoma (ALCL in this case) is well known entity. After the diagnosis was
      established, our patient immediately had been referred to the Department of
      Hematology in order to get appropriate chemotherapy, necessary in such cases.

PMID- 16995846
TI  - Down Syndrome and thyroid gland.
AB  - Down Syndrome (DS) or trisomy 21 (T21) is the most frequent and the best known
      malformation syndrome associated with mental deficiency that appears in human,.
      Average incidence of this syndrome is about 1:700 newborns. Numerous researchers
      noted thyroid disorders in people with Down Syndrome but, clinical symptoms of
      thyroid dysfunction are difficult to separate from DS phenotype. The aim of this
      study was to examine the thyroid function in the patients with DS. Our results
      confirmed higher frequency of thyroid dysfunction in DS patients. Higher values
      of TSH were found in 60,34% of the examined DS patients, which is significantly
      higher value comparing with the control group (p<0,01). Compensated
      hypothyroidism was established in 27,92% of the examined DS patients, and most of
      those (63,23%) were younger than 6 years. The conclusions emphasize the necessity
      of implementation of thyroid function screening program in persons with DS, and
      the need for adequate treatment of its dysfunction. Thus, the symptoms of the
      disease would be alleviated and better physical and mental fitness ensured.

PMID- 16995847
TI  - Immunosuppressive therapy protocols in kidney transplantation in adults.
AB  - In practical terms, regardless of HLA compatibility level, whenever tissues are
      transplanted from one person to another it is essential to suppress the immune
      response of the recipient. A variety of methods are available however, the most
      frequently used ones have the disadvantage of being immunologicaly non specific.
      The consequence is a difficult balance between immunosuppression sufficient to
      prevent the tissue rejection and maintenance of immune system at the level of
      ability to adequately deal with an infection. The goal, not yet achieved, is to
      find a way of generating donor specific immunosuppression that leaves the immune
      machinery otherwise completely intact. The major approaches to immunosuppression
      are described below.

PMID- 16995849
TI  - Comparative determination of xenobiotics adsorption.
AB  - Xenobiotic solutions of different concentrations were analyzed by TLC method
      before and after passing trough the column with adsorbent M and compared with
      adsorption on the active charcoal. The efficiency of adsorption on adsorbent M
      was higher, compared to active charcoal. The best adsorption, in the value 90 -
      100%, have shown certain organochlorine and organophosphorus pesticides, that
      were dissolved in non-aqueous solvents. Efficiency of adsorbent M was also proven
      in vivo, when solutions of tested xenobiotics before adsorption have caused death
      of experimental animals, and after the adsorption on adsorbent M, all treated
      animals have survived and had just mild symptoms of poisoning.

PMID- 16995848
TI  - Influence of two different types of cardioplegia on hemodilution during and after
      cardiopulmonary bypass, postoperative chest-drainage bleeding and consumption of
      donor blood products.
AB  - The aim of this study is to compare the effects of colloidal cardioplegia and
      blood cardioplegia in patients who underwent cardiac surgical procedures with
      cardiopulmonary bypass, and to evaluate their influence on hemodilution, bleeding
      and consumption of donor blood products in a retrospective clinical study. 100
      male patients who underwent cardiac surgical procedure were divided into two
      groups: 50 patients were administered intermittent normotherm or mild hypotherm
      (34 degrees C) Calafiore blood cardioplegia with potassium chloride 14,9%; 50
      patients were administered one initial doses of cold Kirsch - solution followed
      from intermittent cold colloidal cardioplegia using hydroxyethyl starch (HES
      450/0,7). Hemoglobin values after the first dose of cardioplegia were
      significantly lower in the HES-group than in the Calafiore- group). After the
      first dose of cardioplegia platelets count was lower in the HES-group than in the
      Calafiore-group. Hemoglobin and hematocrit values 24h postoperative were lower in
      the HES-group than in the Calafiore-group. There was no difference in chest
      drainage bleeding 12h and 24h postoperative between the groups. The consumption
      of donor erythrocyte concentrate and fresh frozen plasma was significantly higher
      in the HES-than in the Calafiore- group. The choice of either colloidal or blood
      cardioplegia does not influence the postoperative chest-drainage bleeding. The
      results suggest that high molecular colloidal cardioplegia with HES-solution is
      associated with higher hemodilution during and after cardiopulmonary bypass and
      significantly increases the consumption of donor blood products.

PMID- 16995850
TI  - Helicobacter pylori as a promoter of accelerated regeneration, pathological
      differentiation and transformation of normal gastric mucosa into cancerous type.
AB  - The aim of the study was to ascertain presence of Helicobacter pylori in gastric
      carcinoma as a responsible promoter of inflammatory-regenerative changes, which
      lead to pathological differentiation and transformation of normal epithelial
      cells into intestinal type and, in progression, cause epithelial dysplasia that
      develops into early gastric carcinoma. The paper presents prospective study that
      includes clinical, pathohistological and microbiological aspects of
      carcinogenesis initiation in gastric mucosa. The subjects are patients treated at
      Gastroenterohepatology Clinic divided into two groups. One group included 50
      patients with gastric carcinoma while the control group included 50 patients with
      chronic atrophic H. pylori positive gastritis. All the patients were subjected to
      endoscopy as well as biopsy targeted at antrum, lesser curvature and corpus and
      at the region 1-2 cm removed from tumor lesion. We used HUT test to verify H.
      pylori presence in biopsy samples. We analyzed the samples for presence,
      frequency and severity of inflammatory-regenerative, metaplastic and dysplastic
      changes in gastric mucosa and evaluated their meaning for the prognosis. Our
      study confirmed Helicobaster pylori responsibility for inflammatory events in
      gastric mucosa in patients with gastric carcinoma. Slight and mild epithelial
      dysplasia with chronic atrophic gastritis grade I and II coupled with intestinal
      metaplasia may be considered an indicator for early detection of carcinoma. Such
      patients represent risk group for gastric carcinoma development.

PMID- 16995851
TI  - Measuring outcomes in acute neurorehabilitation in General Hospital setting - our
      experience.
AB  - In General Hospital setting, where varieties of patients are included in
      neurorehabilitation process, set of multidisciplinary functional tests were
      established, as a routine in daily work. Tests were done by physiotherapists and
      occupational therapists who were members of rehabilitation team. Our aim was to
      select the tests which can be used as a routine and are applicable for different
      neurological impairments in daily work. Tests were applied to inpatients admitted
      to the Medical, Trauma, Neurology and Neurosurgery wards in the Rashid Hospital,
      DOHMS, Dubai. Fifty inpatients with different neurological impairments admitted
      to totally 8 wards, were tested in the beginning of rehabilitation process and on
      discharge from the hospital. Nine tests were used as standardized tests for
      measuring motor, cognitive, focal impairment, ADL activities and disability:
      Motricity Index, Trunk Control Test, Standing Balance score, Functional
      Ambulation Categories test, Mini Mental State Examination, Canadian Neurological
      Scale, Action Research Arm test, Bartel Index and Functional Independent
      Measurements. FIM, Motricity Index and Trunk Control Test were applicable for all
      tested patients, with required adaptation for different neurological conditions
      within the same score. Other tests were not applicable for all patients as
      routine, but there were very useful for certain number of patients as a
      measurement of functional improvement. It is very important to have proper setup
      of tests, which are simple, reliable and valid for measuring impairment,
      disability and handicap and which can be used as standardized part of assessment
      protocol. Also, they must be applicable for different neurological impairments to
      monitor treatment progress. Combination of tests performed by different
      professionals and comprehensive approach of all team members is very important
      for measuring outcomes in rehabilitation and evaluating patient's impairment and
      disability. Proper hospital setup, optimal number of staff, good communication
      and team work are leading to better outcome in neurorehabilitation process.

PMID- 16995852
TI  - No influence of body composition on serum growth hormone response to acute
      dynamic exercise.
AB  - Physical effort is a strong physiological stimulus that provokes an increase in
      blood growth hormone (GH) concentration. Interactions between GH and body
      composition are very complex. Seven athletes and seven age-matched controls
      completed a single 30-min bout of upright cycling exercise (5 % of VO(2max).) in
      order to estimate the influence of body composition on serum GH concentration
      during exercise. The serum GH concentration was measured in blood samples by
      standard immunoradiometric (IRMA) method. Anthropometric measurements were used
      for the calculation of body composition. There were no significant differences in
      total body mass or body mass index between the groups. The athletes had
      significantly less fat and higher bone and muscle mass. Serum GH concentration
      was 2.39 times higher in the athlets versus the control in the period of rest.
      During acute exercise, the serum GH concentration increased in both groups. No
      statistically significant differences between the groups in serum GH
      concentration were found either during the exercise or in the recovery. No
      correlation between body composition and serum GH concentration was found. Body
      composition depends on the level of physical activities but if the total body
      mass is in physiologycal range it does not influence the serum GH response to
      acute exercise.

PMID- 16995853
TI  - Postnatal - physiological research of the bronchial receptor system development
      on the isolated preparation of the human trachea in vitro.
AB  - Research was done on pharmacological-physiological development of the bronchial
      receptor system on the smooth muscles of trachea in the newborn children, alive
      born and stillborn children. Monitored was the response on: acetylcholine,
      dopamine, histamine and serotonin in different molar concentrations 10(-4), 10(
      3), 10(-2), 10 mol/dm(-3), micromol/dm(-3)). Research was done on tonus of
      tracheal smooth muscles of 23 tracheal preparations taken by autopsy after death
      from different factors. Based on pharmacological-physiological research on the
      preparations of human isolated trachea it was find out that: acetylcholine
      stimulation effect is significant (p>0,01) in 38-41 weeks of pregnancy comparing
      with that in 30-37 weeks of pregnancy (p>0,01), while dopamine stimulation effect
      is significant (p>0,05) in 30-37 pregnancy weeks comparing with the effect of
      acetylcholine and dopamine on the still-born infants of the same pregnancy period
      (p<0,01). Histaminic receptors were developed during intrauterine life after 38
      weeks of pregnancy (p>0,025). Serotonin has caused contraction of the bronchial
      smooth muscles after 30 pregnancy weeks, but response was not significant
      (p<0,01). This suggests that cholinergic and adrenergic system of the airways in
      alive newborn infants develops in parallel intrauterine, contrary to other
      systems which develop in certain extrauterine life phases.

PMID- 16995854
TI  - Two-criteria dental aging method applied to a Bosnian population: comparison of
      formulae for each tooth group versus one formula for all teeth.
AB  - The purpose of this study was to obtain age estimation formulae using the length
      of periodontosis, transparency of the root and root height in each tooth group
      for the current male population in Bosnia and Herzegovina and to compare these
      formulae with Lamendin's and Prince's formulae. The research was undertaken on
      847 single rooted teeth from 200 identified deceased persons, individuals who
      died between the ages of 23 and 85 years. Periodontosis, transparency and root
      height were measured according to Lamendin's procedure. All teeth were grouped in
      two ways: according to the tooth groups and to the age groups. The highest
      coefficients of correlation are obtained for maxillary canines (R = 0,731) and
      mandibular canines (R = 0,706) and the maxillary lateral incisors showed the
      lowest mean error (ME = 6,63 years). In age groups, the lowest mean error was
      obtained in the 40-49 years age group (ME = 5,15 years). Equations developed in
      this study give statistically significantly better age estimations in comparison
      to the original Lamendin and Prince formulae for the whole sample as well as for
      each tooth group, except for mandibular central incisors. Age estimation with
      models developed for each tooth group (except for mandibular lateral incisors)
      was statistically significantly better than models based on the whole sample.

PMID- 16995855
TI  - Osteoarthritis, application of physical therapy proceduers.
AB  - Osteoarthritis (OA) is a group of overlapping disorders, which may have different
      aetiology but similar biological, morphologic and clinical outcome. In
      osteoarthritis, process will not encompass the joint cartilage only, but the
      entire joint, including sub-hondral bone, ligaments, capsule, and sinovial
      membrane and surrounding muscles. Osteoarthritis is a multi-factor disorder of
      sinovial joints, which occurs as result of mechanical and biological factors,
      which destabilise normal hondrocyte function, partitioning of cartilage, extra
      cellular matrix and sub-hondral bone. The earliest changes, which are restricted
      to the joint cartilage surface only, do not cause any subjective feeling. The
      pain in arthrosis occurs (or re-occurs) a bit later, Diagnosis will be determined
      based on clinical exam as well as signs and symptoms present. Symptomatic and
      functional treatment of osteoarthritis as one of rheumatic disorders must be
      taken throughout years, sometimes throughout a lifetime. It encompasses
      application of many medications and physical therapy procedures.

PMID- 16995856
TI  - Position of mandibular joint surface in cenrric relation.
AB  - The position of mandible in centric relation is the initial position in
      prosthodontic rehabilitation. This fact is especially significant today when, due
      to development of implantology, the use of osseointegrated prostheses is
      increasingly discussed. The aim of the study is to define if the peak of the
      articulating surface of mandible in centric relation position is directed towards
      the zenith of madibular fossa, or is in the retroposition. The research was
      conducted on macerated human sculls in anthropometric system, based on objective
      measuring techniques and methods. The results showed that if the zenith of
      mandibular fossa is determined according to the vertical line of the Frankfurt
      horizontal, the peak of the mandibular caput articulating surface is in
      retroposition. The relation of the lower joint surface to the mandibular fossa
      zenith is the same on both right and left side. The correlation coefficient
      demonstrates a high correlation between the sides, highly significant with
      probability level of p<0,01. If the peak of mandibular fossa is determined
      according to the vertical line of the Frankfurt horizontal, the peak of the
      articulating surface of mandibular caput is in retroposition in relation to the
      peak of the upper jaw surface. This original scientific work will help better
      understanding of x-ray analysis and understanding of relationship of TMJ
      surfaces, what is necessary for treatment of TMD and occlusal imbalances.

PMID- 16995857
TI  - Solution NMR structure of a human FGF-1 monomer, activated by a hexasaccharide
      heparin-analogue.
AB  - The 3D structure of a complex formed by the acidic fibroblast growth factor (FGF
      1) and a specifically designed synthetic heparin hexasaccharide has been
      determined by NMR spectroscopy. This hexasaccharide can substitute natural
      heparins in FGF-1 mitogenesis assays, in spite of not inducing any apparent
      dimerization of the growth factor. The use of this well defined synthetic heparin
      analogue has allowed us to perform a detailed NMR structural analysis of the
      heparin-FGF interaction, overcoming the limitations of NMR to deal with the high
      molecular mass and heterogeneity of the FGF-1 oligomers formed in the presence of
      natural heparin fragments. Our results confirm that glycosaminoglycans induced
      FGF-1 dimerization either in a cis or trans disposition with respect to the
      heparin chain is not an absolute requirement for biological activity.

PMID- 16995859
TI  - From pharmacology to immunopharmacology.

PMID- 16995858
TI  - Cell surface nucleolin on developing muscle is a potential ligand for the axonal
      receptor protein tyrosine phosphatase-sigma.
AB  - Reversible tyrosine phosphorylation, catalyzed by receptor tyrosine kinases and
      receptor tyrosine phosphatases, plays an essential part in cell signaling during
      axonal development. Receptor protein tyrosine phosphatase-sigma has been
      implicated in the growth, guidance and repair of retinal axons. This phosphatase
      has also been implicated in motor axon growth and innervation. Insect orthologs
      of receptor protein tyrosine phosphatase-sigma are also implicated in the
      recognition of muscle target cells. A potential extracellular ligand for
      vertebrate receptor protein tyrosine phosphatase-sigma has been previously
      localized in developing skeletal muscle. The identity of this muscle ligand is
      currently unknown, but it appears to be unrelated to the heparan sulfate ligands
      of receptor protein tyrosine phosphatase-sigma. In this study, we have used
      affinity chromatography and tandem MS to identify nucleolin as a binding partner
      for receptor protein tyrosine phosphatase-sigma in skeletal muscle tissue.
      Nucleolin, both from tissue lysates and in purified form, binds to receptor
      protein tyrosine phosphatase-sigma ectodomains. Its expression pattern also
      overlaps with that of the receptor protein tyrosine phosphatase-sigma-binding
      partner previously localized in muscle, and nucleolin can also be found in
      retinal basement membranes. We demonstrate that a significant amount of muscle
      associated nucleolin is present on the cell surface of developing myotubes, and
      that two nucleolin-binding components, lactoferrin and the HB-19 peptide, can
      block the interaction of receptor protein tyrosine phosphatase-sigma ectodomains
      with muscle and retinal basement membranes in tissue sections. These data suggest
      that muscle cell surface-associated nucleolin represents at least part of the
      muscle binding site for axonal receptor protein tyrosine phosphatase-sigma and
      that nucleolin may also be a necessary component of basement membrane binding
      sites of receptor protein tyrosine phosphatase-sigma.

PMID- 16995860
TI  - Evaluation of proinflammatory cytokines and inflammation markers as biomarkers
      for the action of thiazolidinediones in Type 2 diabetes mellitus patients and
      healthy volunteers.
AB  - AIMS: Thiazolidinediones (TZDs) not only enhance cellular glucose transport but
      are reported to have potent anti-inflammatory effects. These effects may play an
      important role in the insulin sensitizing mechanism, and possibly precede the
      effects on parameters of glucoregulation. We sought to investigate whether these
      anti-inflammatory effects could yield early responding biomarkers for TZD action
      in Type 2 diabetes mellitus (T2DM) patients and healthy volunteers (HV) to
      expedite early clinical development of novel compounds. METHODS: We investigated
      the timing of treatment effects on several proinflammatory cytokines and markers
      of inflammation in comparison with effects on typical measures of glucoregulation
      in T2DM patients and HV receiving rosiglitazone 4 mg or placebo twice daily for 6
      weeks. RESULTS: We found a significant reduction in interleukin (IL)-6 [-39.4%,
      confidence interval (CI) - 60.0, - 8.2] and white blood cell count (-18.4%, CI -
      30.2, - 4.5) after 4 weeks of treatment in the T2DM group. These anti
      inflammatory effects did not precede the effects on typical parameters of
      glucoregulation in the T2DM group and there was no significant anti-inflammatory
      response in the HV group. CONCLUSION: We could not identify biomarkers that
      precede the effects of rosiglitazone on parameters of glucoregulation in T2DM or
      that have a significant response in HV. However, the IL-6 response observed in
      this study indicates a potential role for this cytokine as complementary
      biomarker in clinical 'proof of concept' studies with novel TZDs.

PMID- 16995861
TI  - Speed of onset of bronchodilator response to salbutamol inhaled via different
      devices in asthmatics: a bioassay based on functional antagonism.
AB  - AIMS: To evaluate the speed of onset of bronchodilation following salbutamol
      administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a
      dry-powder inhaler (Diskus), as well as the relative potencies of these devices
      in asthmatic patients with methacholine-induced bronchoconstriction. METHODS:
      Eighteen patients inhaled methacholine (MCh) until FEV(1) decreased by 35% of
      control. Following administration of placebo, 200 microg salbutamol or 400 microg
      salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time
      elapsed from drug administration and the appearance of a 90% increase in post-MCh
      forced vital capacity (FVC), FEV(1) and volume-adjusted mid-expiratory flow
      (recovery times). The salbutamol doses to be delivered by the two inhalation
      devices to achieve similar recovery times and the relative potencies of the
      devices were calculated by using the 2-by-2 Finney parallel regression method.
      RESULTS: For all functional variables, recovery times were significantly (P <
      0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be
      delivered by the Diskus to achieve recovery times for FVC, FEV(1) and volume
      adjusted mid-expiratory flow similar to those obtained with 200 microg salbutamol
      administered via the pMDI + Volumatic were 558 (95% CI 537, 579) microg, 395 (95%
      CI 388, 404) microg and 404 (95% CI 393, 415) microg, respectively, and
      corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI
      1.94, 2.02), and 2.02 (95% CI 1.96, 2.07). CONCLUSIONS: Administration of
      salbutamol via the pMDI + Volumatic provides faster reversal of induced
      bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs
      with the pMDI + Volumatic is approximately twice that with the Diskus.

PMID- 16995862
TI  - Plasma concentrations of inhaled corticosteroids in relation to airflow
      obstruction in asthma.
AB  - AIMS: To compare the pharmacokinetic profiles of beclometasone, budesonide,
      fluticasone and mometasone following inhalation in patients with asthma, and
      explore the relationship between lung function and plasma drug concentrations.
      METHODS: Thirty subjects with asthma and a forced expiratory volume in 1 s
      (FEV(1)) ranging from 36 to 138% predicted, inhaled 800 microg beclometasone,
      budesonide and mometasone and 1000 microg fluticasone in random order. Plasma
      drug concentrations were measured over 8 h and the relationship between the area
      under the plasma concentration-time curve (AUC(0-8)) and lung function was
      modelled using linear regression. Estimated AUC(0-8) values at 50 and 100%
      predicted FEV(1) were compared for each drug. RESULTS: Pharmacokinetic profiles
      differed markedly between the drugs. Correlation coefficients for the relation
      between FEV(1)% predicted and AUC(0-8) values for beclometasone, budesonide,
      fluticasone and mometasone were 0.37 (P = 0.05), 0.33 (P = 0.08), 0.25 (P = 0.2)
      and 0.52 (P = 0.004), respectively, and estimated AUC(0-8) values were 1.3 [95%
      confidence interval (CI) 1.0, 1.8], 1.3 (95% CI 1.0, 1.8), 1.4 (95% CI 0.9, 2.2)
      and 2.2 (95% CI 1.3, 3.5) times higher for the four drugs, respectively, at 100
      compared with 50% predicted FEV(1.) CONCLUSION: The higher plasma concentrations
      of inhaled corticosteroids in patients with a higher FEV(1)% predicted suggests
      that, for any given dose, these patients will be at greater risk of developing
      adverse systemic effects with long-term use.

PMID- 16995863
TI  - A Bayesian approach for population pharmacokinetic modelling of sirolimus.
AB  - AIMS: To explore a Bayesian approach for the pharmacokinetic analysis of
      sirolimus concentration data arising from therapeutic drug monitoring (poorly
      informative concentration-time point design), and to explore possible covariate
      relationships for sirolimus pharmacokinetics. METHODS: Sirolimus concentration
      time data were available as part of routine clinical care from 25 kidney
      transplant recipients. Most samples were taken at or near the trough time point
      at steady state. The data were analyzed using a fully conditional Bayesian
      approach with PKBUGS (v 1.1)/WinBUGS (v 1.3). Features of the data included
      noncompliance and missing concentration measurements below the limit of
      sensitivity of the assay. Informative priors were used. RESULTS: A two
      compartment model with proportional residual error provided the best fit to the
      data (consisting of 315 sirolimus concentration-time points). The typical value
      for the apparent clearance (CL/F ) was 12.5 l h(-1) at the median age of 44
      years. Apparent CL was found to be inversely related to age with a posterior
      probability of a clinically significant effect of 0.734. CONCLUSIONS: A
      population pharmacokinetic model was developed for sirolimus using a novel
      approach. Bayesian modelling with informative priors allowed interpretation of a
      significant covariate relationship, even using poorly informative data.

PMID- 16995864
TI  - Pharmacokinetics of subcutaneously administered etanercept in subjects with
      psoriasis.
AB  - AIMS: To present the results of the pharmacokinetic analysis of the concentration
      time profiles of etanercept, a soluble receptor tumour necrosis factor (TNF)
      antagonist, in more than 1300 subjects with psoriasis. METHODS: Pharmacokinetic
      samples were collected in one phase-2 and two phase-3 placebo-controlled,
      randomized clinical trials. Study 1 evaluated a 25-mg twice weekly (BIW)
      etanercept dosing regimen administered by subcutaneous (s.c.) injection for 24
      weeks. Study 2 evaluated 25-mg BIW and 50-mg BIW s.c. doses for 12 weeks. Study 3
      evaluated 25 mg once weekly (QW), 25 mg BIW and 50 mg BIW s.c. doses for 24
      weeks. RESULTS: The mean +/- SD steady-state predose serum concentrations of
      etanercept for the 25-mg BIW arm at 12 weeks in study 1 were 1590 +/- 885 ng ml(
      1). In study 2, mean +/- SD etanercept steady-state concentrations at 12 weeks
      were 1900 +/- 1110 ng ml(-1) in the 25-mg BIW group and 3830 +/- 1870 ng ml(-1)
      in the 50-mg BIW group. The mean +/- SD steady-state predose serum concentrations
      of etanercept at 12 weeks in study 3 were 768 +/- 475 ng ml(-1) for the 25-mg QW
      regimen, 1990 +/- 1030 ng ml(-1) for the 25-mg BIW regimen and 4020 +/- 2100 ng
      ml(-1) for the 50-mg BIW regimen. CONCLUSIONS: Pharmacokinetic results were
      highly consistent across clinical trials. The concentration-time profiles
      displayed dose proportionality. Etanercept concentrations in subjects with
      psoriasis are similar to the concentrations in subjects with rheumatoid
      arthritis.

PMID- 16995865
TI  - Investigation on pharmacokinetics of mycophenolic acid in Chinese adult renal
      transplant patients.
AB  - AIMS: To characterize the pharmacokinetics of mycophenolic acid (MPA) in Chinese
      renal transplant patients. METHODS: Thirty-one renal transplant patients (17
      male, 14 female) receiving mycophenolate mofetil (MMF) 1.0 g twice daily were
      included in this study. A pharmacokinetic study was performed during an interval
      in dosing after steady state had been reached within 2 months after
      transplantation. The plasma MPA concentration were measured by high-performance
      liquid chromatography (HPLC) at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the
      administration of a single dose. Pharmacokinetic parameters were calculated with
      3P97 software. SAS software was used for statistical analysis. Multiple linear
      regression analysis was used to determine limited sampling approaches. RESULTS:
      The mean peak plasma concentration (C(max)) and area under the concentration-time
      curve (AUC(0-12)) were 19.67 +/- 8.21 microg ml(-1) and 52.16 +/- 12.50 microg h
      ml(-1), but there was large variability in these pharmacokinetic parameters.
      Regression analysis between each plasma concentration and AUC for the limited
      sampling strategy of MMF therapeutic drug monitoring demonstrated that each of
      the concentrations at 0.5, 1, 4 and 10 h was positively correlated with AUC (r =
      0.60, P = 0.0004; r = 0.60, P = 0.0003; r = 0.61, P = 0.0003; r = 0.64, P =
      0.0001, respectively). The combined use of these four samples explained over 90%
      of the variance in the total (nine-point) AUC(0-12). A formula was obtained for
      the assessment of MPA AUC based on four samples: MPA AUC = 12.61 + 0.37 x C(0.5)
      + 0.49 x C(1) + 3.22 x C(4) + 8.17 x C(10). CONCLUSIONS: Chinese renal transplant
      patients had higher median AUCs than caucasians and African-Americans. As in
      other studies, there was large interindividual variability. A limited four-point
      AUC was in good agreement with the 12-h AUC and provided the basis of a
      predictive formula.

PMID- 16995866
TI  - Exposure to thiopurine drugs through breast milk is low based on metabolite
      concentrations in mother-infant pairs.
AB  - AIMS: To determine infant exposure to 6-thioguanine and 6-methylmercaptopurine
      nucleotides (6-TGN and 6-MMPN, respectively) during maternal use of azathioprine
      in breastfeeding. METHODS: Mother-infant pairs provided blood for determination
      of 6-TGN and 6-MMPN concentrations, and TPMT genotype. RESULTS: Four women taking
      azathioprine 1.2-2.1 mg kg(-1) day(-1) and their infants were studied. All had
      the wild-type TPMT genotype. Maternal 6-TGN and 6-MMPN concentrations ranged from
      234 to 291 and 284 to 1178 pmol per 8 x 10(8) red blood cells, respectively, and
      were consistent with those associated with improved therapeutic outcomes. Neither
      6-TGN nor 6-MMPN was detected in any of the infants, despite a sensitive assay.
      CONCLUSIONS: The data suggest that azathioprine may be 'safe' during
      breastfeeding in patients with the wild-type TPMT genotype ( approximately 90% of
      caucasian patients) taking 'normal' doses.

PMID- 16995867
TI  - Relationship of glutathione S-transferase genotypes with side-effects of pulsed
      cyclophosphamide therapy in patients with systemic lupus erythematosus.
AB  - AIMS: Cyclophosphamide (CTX) is an established treatment of severe systemic lupus
      erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple
      glutathione S-transferases (GSTs). However, data are lacking on the relationship
      between the short-term side-effects of CTX therapy and GST genotypes. In the
      present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on
      the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection
      incidences induced by pulsed CTX therapy were evaluated in patients SLE. METHODS:
      DNA was extracted from peripheral leucocytes in patients with confirmed SLE
      diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase
      chain reaction (PCR)-multiplex procedure, whereas the GSTP1 codon 105
      polymorphism (Ile-->Val) was analyzed by a PCR-restriction fragment length
      polymorphism (RFLP) assay. RESULTS: Our study demonstrated that SLE patients
      carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*-105I/V
      (heterozygote) and GSTP1*-105 V/V (homozygote)] had an increased risk of
      myelotoxicity when treated with pulsed high-dose CTX therapy (Odds ratio (OR)
      5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger
      than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total
      CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients
      with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI
      toxicity when treated with an initial pulsed high-dose CTX regimen (OR 3.33, 95%
      CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly
      alter the risks of these short-term side-effects of pulsed high-dose CTX therapy
      in SLE patients. CONCLUSIONS: The GSTP1 codon 105 polymorphism, but not GSTM1 or
      GSTT1 null mutations, significantly increased the risks of short-term side
      effects of pulsed high-dose CTX therapy in SLE patients. Because of the lack of
      selective substrates for a GST enzyme phenotyping study, timely detection of this
      mutation on codon 105 may assist in optimizing pulsed high-dose CTX therapy in
      SLE patients.

PMID- 16995868
TI  - Two cases of thiopurine methyltransferase (TPMT) deficiency--a lucky save and a
      near miss with azathioprine.
AB  - BACKGROUND: The association between thiopurine methyltransferase (TPMT)
      deficiency and myelosuppression with azathioprine is well recognized. Two cases
      are presented that illustrate the very different outcomes that may occur with
      azathioprine in patients with TPMT deficiency, which affects 0.3-0.6% of
      caucasians. CASE 1: The first patient's TPMT deficiency was identified following
      hospitalization for pancytopenia attributed to azathioprine. CASE 2: The second
      patient was identified as deficient early in treatment and myelosuppression was
      avoided by treating with a greatly decreased dose (25 mg per week). CONCLUSIONS:
      Testing for TPMT ideally should be performed in every patient commencing a
      thiopurine drug.

PMID- 16995869
TI  - A comparison of the effect of ciclosporin and sirolimus on the pharmokinetics of
      mycophenolate in renal transplant patients.
AB  - AIM: To compare the pharmacokinetics of mycophenolic acid when given with either
      ciclosporin or sirolimus, and investigate in vitro the potential effect of
      ciclosporin, sirolimus, tacrolimus and everolimus on mycophenolic acid
      metabolism. METHODS: In renal transplant patients given mycophenolate mofetil in
      combination with ciclosporin (n = 19) or sirolimus (n = 12), concentration-time
      profiles of mycophenolic acid, mycophenolic-acid-phenyl-glucuronide, mycophenolic
      acid-acyl-glucuronide and mycophenolic-acid-phenyl-glucoside were determined at
      one month post-transplant. The effect of immunosuppressive drugs on mycophenolic
      acid glucuronidation and glycosylation was investigated in vitro using human
      liver microsomes. RESULTS: The mean mycophenolic acid AUC(0-9 h) in the sirolimus
      group was 44.9 mg h(-1) L(-1) (95% CI: 34.7-55.1), vs. 30.5 mg h(-1) L(-1) (95%
      CI: 25.4-35.6) in the ciclosporin group, corresponding to 1.5-fold dose
      normalized difference (95% CI: 1.1-1.9; P < 0.05). In addition, the
      metabolite/mycophenolic acid AUC(0-9 h) ratios were significantly higher in
      patients cotreated with ciclosporin than with sirolimus, giving values of 1.8
      fold (95% CI: 1.3-2.3; P = 0.0009), 2.6-fold (95% CI: 2.0-3.3; P < 0.0001) and
      4.3-fold (95% CI: 2.6-6.0; P = 0.0016) for mycophenolic-acid-phenyl-glucuronide,
      mycophenolic-acid-acyl-glucuronide and mycophenolic-acid-phenyl-glucoside,
      respectively. In vitro, none of the immunosuppressive drugs tested inhibited
      mycophenolic acid metabolism. CONCLUSION: Patients taking mycophenolate mofetil
      and sirolimus experience a higher exposure to mycophenolic acid and a lower
      exposure to mycophenolic acid metabolites than those being treated with
      mycophenolate mofetil and ciclosporin. This interaction is probably not caused by
      inhibition of mycophenolic acid glucuronidation or glycosylation, but is more
      likely to be due to the influence of ciclosporin on the excretion of mycophenolic
      acid metabolites into bile.

PMID- 16995871
TI  - Absence of an interaction between iron and mycophenolate mofetil absorption.
AB  - AIM: To determine whether concomitant iron affects the absorption of
      mycophenolate mofetil. METHODS: An open-label, single centre, randomized,
      crossover trial was conducted in 16 healthy males. Fasting subjects received
      mycophenolate mofetil alone (treatment A) or co-administered with iron (treatment
      B). RESULTS: The mycophenolic acid AUC(0,24 h) for treatments A and B were 42.5
      +/- 10.5 and 44.7 +/- 12.4 microg ml(-1) h, respectively. anova modelling showed
      the relative bioavailability of mycophenolate mofetil to be similar for the two
      treatments (90% confidence interval 0.92, 1.19). CONCLUSIONS: There was no
      interaction between mycophenolate mofetil and iron supplements administered
      concomitantly to healthy fasting subjects.

PMID- 16995870
TI  - Impact of citrus soft drinks relative to grapefruit juice on ciclosporin
      disposition.
AB  - AIMS: A recent case report had suggested a citrus soft drink (Sun Drop) may have
      caused clinically relevant elevations in ciclosporin levels through a grapefruit
      juice-like mechanism via inactivation of intestinal cytochrome P450 3A4 (CYP3A4).
      This study was conducted to investigate the effect of grapefruit juice and citrus
      sodas Sun Drop and Fresca, the latter soda containing 83-fold higher
      concentration of the proposed CYP3A4 inhibitor bergamottin than Sun Drop,
      relative to water on oral ciclosporin pharmacokinetics. METHODS: In a randomized
      four-way crossover study with a washout of at least 1 week, 12 healthy volunteers
      received a single oral dose of ciclosporin (Neoral) with Sun Drop, Fresca,
      grapefruit juice and water (control). Each drink (591 ml) was consumed twice on
      the prior day and three times on the study day. Whole blood concentrations of
      ciclosporin were measured up to 24 h with a fluorescence polarization
      immunoassay. RESULTS: Grapefruit juice increased area under the concentration
      time curve by 186% (P < 0.0001; 95% confidence interval of mean difference 3302
      6240 ng ml h(-1)) and peak concentration by 150% (P < 0.0001) of ciclosporin with
      a significant decrease in oral clearance of 43% (P < 0.0001) when compared with
      water. Neither citrus soda altered significantly ciclosporin pharmacokinetic
      variables; changes in mean values ranged from +/- 3 to 11% of the corresponding
      water value. CONCLUSION: Although our results do not support a clinically
      relevant grapefruit juice-like interaction between oral ciclosporin and citrus
      constituent containing sodas Sun Drop or Fresca, an effect in the setting of
      chronic ciclosporin therapy cannot be ruled out.

PMID- 16995873
TI  - Characteristic expression of globotriaosyl ceramide in human ovarian carcinoma
      derived cells with anticancer drug resistance.
AB  - The transporter protein genes and lipids in human ovarian carcinoma-derived KF28
      cells with anticancer-drug-sensitive properties were compared with those in
      resistant cells, taxol-resistant KF28TX, cisplatin-resistant KFr13, and taxol-
      and cisplatin-resistant KFr13TX, to identify the molecules required for
      anticancer-drug resistance. In accordance with previous reports, taxol and
      cisplatin resistance was closely correlated with expression of the multidrug
      resistance 1 and bile acid export pump, and multidrug resistance-associated
      protein 2 genes, respectively. In addition, we found a distinct difference in
      glycosphingolipids between the sensitive and resistant cells. Although GlcCer was
      the major glycolipid (83.0%) in sensitive cells, GalCer, LacCer and,
      particularly, Gb(3)Cer were characteristically increased in all resistant cells,
      irrespective of whether the resistance was to taxol or cisplatin, and comprised
      65-84% of total glycosphingolipids. GM3, which was present at 0.04 microg/mg dry
      weight in the sensitive cells, showed a twofold increase in the taxol-resistant
      cells, but was absent in the cisplatin-resistant cells. The altered glycolipid
      composition was proven to be due to enhanced or suppressed expression of the
      respective sugar transferase genes. In addition, the ceramide moiety of ceramide
      monohexoside in the sensitive cells constituted 83% of non-hydroxy fatty acids,
      but that in the resistant cells comprised 67-74% of alpha-hydroxy fatty acids.
      Thus, cells containing Gb(3)Cer with alpha-hydroxy fatty acids were found to
      survive selectively in the presence of taxol and cisplatin, and modification of
      the glycolipid structure was revealed to occur in association with anticancer
      drug resistance.

PMID- 16995874
TI  - ZD6474 induces growth arrest and apoptosis of GIST-T1 cells, which is enhanced by
      concomitant use of sunitinib.
AB  - ZD6474 (Zactima, AstraZeneca, Macclesfield, UK) is an orally available, small
      molecule inhibitor of vascular endothelial growth factor receptor-2 and epidermal
      growth factor receptor tyrosine kinases, with additional activity versus
      rearranged during transfection (RET). This study explored the effect of ZD6474 in
      gastrointestinal stromal tumor-T1 (GIST-T1) cells that possess a gain of function
      mutation in exon 11 of the c-KIT gene. ZD6474 induced growth arrest and apoptosis
      of GIST-T1 cells in association with blockade of c-Kit and its downstream
      effectors, including Akt and extracellular signal-regulated kinase (ERK). ZD6474
      treatment also blocked the mammalian target of rapamycin (mTOR), which lies
      downstream of Akt and ERK. Interestingly, when ZD6474 was combined with sunitinib
      (SU11248; Sutent, Pfizer, Kalamazoo, MI, USA), a class III and V receptor
      tyrosine kinase inhibitor, the ZD6474-mediated growth inhibition was potentiated
      in association with further down-regulation of the mTOR targets p-p70S6K and p-4E
      BP-1. The combination of ZD6474 and sunitinib should be investigated further.

PMID- 16995875
TI  - Potential role of natural killer cells in controlling growth and infiltration of
      AIDS-associated primary effusion lymphoma cells.
AB  - Natural killer (NK) cells are an important component of the innate immune
      response against microbial infections and tumors. Direct involvement of NK cells
      in tumor growth and infiltration has not yet been demonstrated clearly. Primary
      effusion lymphoma (PEL) cells were able to produce tumors and ascites very
      efficiently with infiltration of cells in various organs of T-, B- and NK-cell
      knock-out NOD/SCID/gammac(null) (NOG) mice within 3 weeks. In contrast, PEL cells
      formed small tumors at inoculated sites in T- and B-cell knock-out NOD/SCID mice
      with NK-cells while completely failing to infiltrate into various organs.
      Immunosupression of NOD/SCID by treatment with an antimurine TM-beta1 antibody,
      which transiently abrogates NK cell activity in vivo, resulted in enhanced
      tumorigenicity and organ infiltration in comparison with non-treated NOD/SCID
      mice. Activated human NK cells inhibited tumor growth and infiltration in NOG
      mice. Our results suggest that NK cells play an important role in growth and
      infiltration of PEL cells, and activated NK cells could be a promising
      immunotherapeutic tool against tumor or virus-infected cells either alone or in
      combination with conventional therapy. The rapid and efficient engraftment of PEL
      cells in NOG mice also suggests that this new animal model could provide a unique
      opportunity to understand and investigate the mechanism of pathogenesis and
      malignant cell growth.

PMID- 16995876
TI  - Amrubicin induces apoptosis in human tumor cells mediated by the activation of
      caspase-3/7 preceding a loss of mitochondrial membrane potential.
AB  - Amrubicin, a completely synthetic 9-aminoanthracycline derivative, inhibits cell
      growth by stabilizing a topoisomerase II-DNA complex. This study was designed to
      examine the apoptosis induced in human leukemia U937 cells by amrubicin and its
      active metabolite amrubicinol. Amrubicin, amrubicinol and other antitumor agents,
      such as daunorubicin and etoposide, induced typical apoptosis with characteristic
      nuclear morphological change and DNA fragmentation. Measuring the population of
      sub-G(1) phase cells, it was found that under conditions where cell growth was
      inhibited by either amrubicin or amrubicinol, U937 cells underwent apoptotic cell
      death in a dose-dependent manner accompanied by an arrest of the cell cycle at
      G(2)/M. Furthermore, amrubicin- and amrubicinol-induced apoptosis was mediated by
      the activation of caspase-3/7, but not caspase-1, preceding a loss of
      mitochondrial membrane potential. These results indicate that both a reduction in
      mitochondrial membrane potential and the activation of caspase-3/7 are key events
      in the apoptosis induced by amrubicin and amrubicinol as well as the other
      antitumor agents. In addition, studies with oligomycin suggested that the
      apoptosis induced by amrubicin and amrubicinol involved substantially different
      pathways from that triggered by daunorubicin and etoposide. Oligomycin blocked
      the etoposide-induced increase in the number of sub-G(1) phase cells without
      preventing the activation of caspase-3/7, and had no inhibitory effect on the
      expansion of the sub-G(1) population in daunorubicin-treated cells, whereas
      apoptosis-related changes caused by amrubicin and amrubicinol were suppressed in
      the presence of oligomycin.

PMID- 16995877
TI  - Prognostic significance of HLA class I expression in osteosarcoma defined by anti
      pan HLA class I monoclonal antibody, EMR8-5.
AB  - With the goal of establishing efficacious peptide-based immunotherapy for
      patients with bone and soft tissue sarcomas, we previously identified the
      cytotoxic T lymphocyte-defined osteosarcoma antigenic gene Papillomavirus binding
      factor. The present study was designed to determine the status of HLA class I
      expression in osteosarcoma and other bone and soft tissue sarcomas. Seventy-four
      formalin-fixed paraffin-embedded specimens of various bone and soft tissue
      sarcomas, including 33 osteosarcomas, were stained with the anti-HLA class I
      monoclonal antibody EMR8-5, which we recently generated. The expression of HLA
      class I was lost or downregulated in 46 of these specimens (62%). With respect to
      osteosarcoma, loss or downregulation of HLA class I expression was seen in 13
      (52%) of 25 primary tumors and seven (88%) of eight metastatic tumors. In six of
      11 HLA class I-negative osteosarcoma specimens, the expression of beta-2
      microglobulin was also lost. Subsequently the prognostic significance of HLA
      class I expression was analyzed in 21 patients with osteosarcoma who had
      completed multidrug neoadjuvant chemotherapy and undergone adequate surgery.
      Patients with osteosarcoma highly expressing HLA class I showed significantly
      better overall and event-free survival than those with HLA class I-negative
      osteosarcoma. In contrast, such prognostic significance of HLA class I expression
      was not found in 15 patients with malignant fibrous histiocytoma of soft tissue.
      These findings suggest that the class I-restricted cytotoxic T lymphocyte pathway
      plays a major role in immune surveillance of patients with osteosarcoma.

PMID- 16995878
TI  - Potential prophylactic value of bovine colostrum in necrotizing enterocolitis in
      neonates: an in vitro study on bacterial attachment, antibody levels and cytokine
      production.
AB  - Necrotizing enterocolitis (NEC) is an important disease of low birth-weight
      neonates. The immaturity of the gut mucosa may result in close contact between
      the host epithelium and microorganisms which are normally confined to the gut
      lumen. Damage of the mucosa due to endotoxin, cytokine production or other
      factors is believed to then occur. The aim of this study was to determine whether
      spray-dried bovine colostrum demonstrated potential in vitro as a prophylactic
      for NEC. Antiadherence was measured using a tissue culture assay and antibody
      levels against Enterobacteriaceae were determined by ELISA. The effect of bovine
      colostrum on the production of cytokines implicated in NEC was determined by a
      multiplex bead assay. Enterobacter cloacae, Klebsiella oxytoca, Escherichia coli,
      Serratia marcescens and Klebsiella pneumoniae ssp. pneumoniae were common in both
      NEC positive and NEC negative infants and IgA and IgG1 antibodies to these
      species were present in the bovine colostrum. Pretreatment with bovine colostrum
      produced a significant decrease (P<0.001) in attachment of bacteria to HT-29
      cells. Bovine colostrum significantly increased the production of IL-8 in HT-29
      cells and IL-8, IL-6 and TNF-alpha in THP-1 cells (P<0.001). The potential of
      bovine colostrum to increase the production of inflammatory mediators could limit
      its usefulness.

PMID- 16995879
TI  - The immunoglobulin A1 proteinase from Streptococcus pneumoniae is inhibited by
      tetracycline compounds.
AB  - Streptococcus pneumoniae produces a zinc-dependent proteinase that cleaves human
      immunoglobulin (Ig) A1 in the hinge region. This metalloproteinase is
      hypothesized to act as a virulence factor by allowing S. pneumoniae to evade the
      protection provided by IgA1, thus enhancing its ability to colonize the human
      nasopharyngeal region. No biologically compatible inhibitors of this enzyme have
      been identified. We determined that doxycycline and a chemically modified
      tetracycline inhibit this enzyme in vitro at low micromolar concentrations.

PMID- 16995880
TI  - A subset of Actinobacillus pleuropneumoniae in vivo induced promoters respond to
      branched-chain amino acid limitation.
AB  - Actinobacillus pleuropneumoniae is the causative agent of a necrotizing
      hemorrhagic pleuropneumonia in swine. In this study, we investigate the
      possibility that the limitation of branched-chain amino acids is a stimulus that
      A. pleuropneumoniae will encounter during infection and will respond to by up
      regulation of genes involved in branched-chain amino acid biosynthesis and
      virulence. Actinobacillus pleuropneumoniae genetic loci that are specifically
      induced during infection were screened in vitro for expression in response to
      limitation of branched-chain amino acids. Of 32 in vivo induced promoter clones
      screened in vitro, eight were induced on chemically defined medium without
      isoleucine, leucine and valine as compared to complete chemically defined medium.
      We identify the genomic context of each clone and discuss its relevance to
      branched-chain amino acid limitation and virulence. We conclude that limitation
      of branched-chain amino acids is a cue for expression of a subset in vivo induced
      genes, including not only genes involved in the biosynthesis of branched-chain
      amino acids, but also other genes that are induced during infection of the
      natural host. These results suggest that limitation of branched-chain amino acids
      may be one of an array of environmental cues responsible for the induction of
      virulence-associated genes in A. pleuropneumoniae.

PMID- 16995881
TI  - Dendritic cells, but not macrophages or B cells, activate major
      histocompatibility complex class II-restricted CD4+ T cells upon immune-complex
      uptake in vivo.
AB  - Professional antigen-presenting cells (APC) are able to process and present
      exogenous antigen leading to the activation of T cells. Antigen-immunoglobulin
      (Ig)G complexes (IC) are much more efficiently processed and presented than
      soluble antigen. Dendritic cells (DC) are known for their ability to take up and
      process immune complex (IC) via FcgammaR, and they have been shown to play a
      crucial role in IC-processing onto major histocompatibility complex (MHC) class I
      as they contain a specialized cross-presenting transport system required for MHC
      class I antigen-processing. However, the MHC class II-antigen-processing pathway
      is distinct. Therefore various other professional APC, like macrophages and B
      cells, all displaying FcgammaR, are thought to present IC-delivered antigen in
      MHC class II. Nonetheless, the relative contribution of these APC in IC
      facilitated antigen-presentation for MHC class II in vivo is not known. Here we
      show that, in mice, both macrophages and DC, but not B cells, efficiently capture
      IC. However, only DC, but not macrophages, efficiently activate antigen-specific
      MHC class II restricted CD4(+) T cells. These results indicate that mainly DC and
      not other professional APC, despite expressing FcgammaR and MHC class II,
      contribute significantly to IC-facilitated T cell activation in vivo under steady
      state conditions.

PMID- 16995883
TI  - Multiple myeloma patients with CKS1B gene amplification have a shorter
      progression-free survival post-autologous stem cell transplantation.
AB  - The prevalence and prognostic relevance of recurrent gains of CKS1B (cyclin
      kinase subunit 1B) gene at chromosome 1q21 region was investigated by interphase
      fluorescence in situ hybridisation in a cohort of 99 multiple myeloma (MM)
      patients treated with intensive chemotherapy followed by autologous stem cell
      transplantation. CKS1B amplification (3-8 CKS1B signals) was detected in 31of 99
      (31%) patients and was associated with deletions of p53 (P = 0.003) and 13q (P =
      0.039) but not with translocation t(11;14) or t(4;14). CKS1B amplification was
      associated with bone marrow plasmacytosis (P = 0.02), but there was no
      correlation with patient age, gender, disease stage, lytic bone lesions, albumin,
      creatinine, C-reactive protein or beta-2 microglobulin levels. Patients with
      CKS1B amplification had a significantly shorter progression-free survival than
      those without such amplification (18.5 vs. 25.7 months, P = 0.035). Likewise, a
      shorter overall survival (44.8 months vs. not reached) was observed; however, the
      difference did not reach statistical significance (P = 0.20). Seven patients had
      paired bone marrows obtained at diagnosis and at relapse, the percentage of cells
      with CKS1B amplification and the level of amplification were significantly
      increased in the relapse marrows. In this cohort of patients, CKS1B was
      frequently amplified in MM and may represent genetic instability associated with
      disease progression.

PMID- 16995882
TI  - Effects of microflora on the neonatal development of gut mucosal T cells and
      myeloid cells in the mouse.
AB  - Colonization with commensal flora in very early life may profoundly influence
      intestinal lymphoid development and bias later immune responses. We defined gut
      homing T cell phenotypes and the influence of flora on intestinal immune
      development in mice. Intestinal T cells were phenotyped and quantified in
      conventional (CV), germfree (GF) and conventionalized germfree (GF/CV) neonatal
      mice by immunohistochemistry. Mucosal adressin cell adhesion molecule 1 (MAdCAM
      1) was expressed by mucosal vessels at birth in CV and GF mice and was more
      prevalent in CV than GF small intestine, but was distributed similarly and did
      not change with age. Less MAdCAM-1 was expressed in the colon; its distribution
      became restricted after weaning, with no difference between CV and GF mice.
      CD3(+)beta(7) (+) cells were present in similar numbers in CV and GF intestine at
      birth. They were CD62L(-) in CV mice and were accompanied by further
      CD3(+)beta(7) (+)CD62L(-) T cells as development progressed, but in GF and GF/CV
      intestine they expressed CD62L and numbers did not change. IEL numbers increased
      at weaning in CV mice in both small and large intestine, but showed delayed
      development in GF intestine. Macrophages were present at high levels from birth
      in GF intestine, but dendritic cells did not develop until day 16. Thus, fetus
      derived T cells seed the intestinal lamina propria before birth via beta-MadCAM
      interactions. Their activation status depends on the microbiological status of
      the dam, and without a commensal flora they remain naive. We propose that these
      cells regulate antigen responsiveness of the developing mucosal T cell pool.

PMID- 16995884
TI  - Reconstitution of the T-cell repertoire following treatment with alemtuzumab
      (anti-CD52 monoclonal antibody) in patients with B-cell chronic lymphocytic
      leukaemia.
AB  - In this pilot study, T-cell receptor B-variable (TCR-BV) gene usage in CD4 and
      CD8 T cells was assessed, by real-time polymerase chain reaction, as well as
      complementarity-determining region 3 (CDR3)-length polymorphism, before and after
      therapy in five patients with B-cell chronic lymphocytic leukaemia who received
      alemtuzumab (anti-CD52 monoclonal antibody) as first-line therapy. A decline in
      expression of most BV family genes in both CD4 and CD8 T cells was observed after
      alemtuzumab treatment, which was followed by a gradual increase in most BV
      families during long-term follow-up. After treatment, CDR3-length polymorphism
      showed an even more restricted pattern in CD4 T cells compared with pretreatment,
      with a shift towards a monoclonal/oligoclonal pattern. The clonally restricted
      pattern was significantly reduced in CD4 (P < 0.01) but not in CD8 T cells. This
      was followed by a gradual increase in the number of peaks within the CDR3 region
      of the different TCR-BV families, i.e. a polyclonal repertoire, during long-term
      follow-up. A restricted CDR3 pattern became even more restricted after treatment,
      but normalised during unmaintained follow-up. These results indicate that
      perturbations in the T-cell alterations following alemtuzumab are complex and
      include not only changes in CD4/CD8 T-cell numbers but also a highly restricted T
      cell repertoire especially in CD4 T cells.

PMID- 16995885
TI  - Severe mucositis is associated with reduced survival after autologous stem cell
      transplantation for lymphoid malignancies.
AB  - Mucositis is a known complication of autologous stem cell transplantation (ASCT).
      This study retrospectively reviewed 191 patients with lymphoid malignancies
      undergoing ASCT following a uniform mobilising regimen of etoposide (VP
      16)/granulocyte colony-stimulating factor and a uniform high-dose preparative
      regimen of busulfan/cyclophosphamide/VP-16. Eighty-seven patients experienced
      severe mucositis (modified Oral Mucositis Assessment Scale > or =1). Patient
      characteristics compared between mucositis groups were balanced according to
      disease status, prior exposure to radiation therapy, time from radiation therapy
      and actual body weight. Log-rank analysis revealed that severe mucositis was
      associated with inferior overall survival (P = 0.002). A 12-month landmark
      analysis showed this difference in survival occurred within 1 year post
      transplant. Multivariate analysis of all-cause mortality showed lower
      pretransplant albumin and severe mucositis to be significant risk factors.
      Multivariate analysis for relapse mortality revealed severe mucositis to be a
      risk factor (P = 0.047), while lower pretransplant albumin was significant for
      non-relapse mortality (NRM; P = 0.009). Kaplan-Meier estimates of survival based
      on relapse and NRM were significantly worse for patients with severe mucositis.
      Reduced pretransplant forced expiratory volume in 1 s (FEV(1)) and carbon
      monoxide (CO) diffusing capacity (DLCO) were also associated with severe
      mucositis. Our data suggest that studies of new treatment strategies for
      mucositis should include relapse and survival endpoints and that pretransplant
      factors, such as FEV(1) and DLCO may be useful to risk-stratify patients entered
      onto such trials.

PMID- 16995886
TI  - A family with hereditary thrombocythaemia and normal genes for thrombopoietin and
      c-Mpl.
AB  - Hereditary thrombocythaemia (HT) is an inherited autosomal dominant disorder.
      Recent studies reported six different mutations, four within the thrombopoietin
      (TPO) gene and two within c-Mpl (TPO receptor) gene in six unrelated families
      with HT. This study investigated the molecular basis of hereditary
      thrombocythaemia in an Israeli-Jewish family. We screened the genes for TPO and c
      Mpl by amplification and sequencing of all the corresponding exons including
      exon/intron boundaries and promoters. In addition, plasma levels of TPO and
      erythropoietin (EPO) were measured. No abnormality in the TPO/c-Mpl genes has
      been identified in affected HT family members. Plasma TPO and EPO levels were
      found to be normal/low or normal respectively in the individuals affected. In
      conclusion, lack of a molecular lesion within either TPO or cMpl genes indicate
      that HT may be caused by factors other than TPO-cMpl axis in this family.

PMID- 16995887
TI  - Preoperative atrial cardiomyocyte ionic currents and postoperative AF: important
      insights into what is not the mechanism.

PMID- 16995888
TI  - Insights into the problems that language barriers may pose for the medical
      interview.

PMID- 16995889
TI  - Comment on "Patterns of communication through interpreters: a detailed
      sociolinguistic analysis".

PMID- 16995890
TI  - Beliefs about asthma and complementary and alternative medicine in low-income
      inner-city African-American adults.
AB  - BACKGROUND: The gap in asthma prevalence, morbidity, and mortality is increasing
      in low-income racial/ethnic minority groups as compared with Caucasians. In order
      to address these disparities,alternative beliefs and behaviors need to be
      identified. OBJECTIVE: To identify causal models of asthma and the context of
      conventional prescription versus complementary and alternative medicine(CAM) use
      in low-income African-American (AA) adults with severe asthma. DESIGN:
      Qualitative analysis of 28 in-depth interviews. PARTICIPANTS: Twenty-six women
      and 2 men, aged 21 to 48, who self-identified as being AA, low-income, and an
      inner-city resident. APPROACH: Transcripts of semi-structured in-depth
      qualitative interviews were inductively analyzed using the constant comparison
      approach. RESULTS: Sixty-four percent of participants held biologically correct
      causal models of asthma although 100% reported the use of at least 1 CAM for
      asthma. Biologically based therapies, humoral balance, and prayer were the most
      popular CAM. While most subjects trusted prescription asthma medicine, there was
      a preference for integration of CAM with conventional asthma treatment.
      Complementary and alternative medicine was considered natural, effective, and
      potentially curative. Sixty-three percent of participants reported non adherence
      to conventional therapies in the 2 weeks before the research interview. Neither
      CAM nor nonmedical causal models altered most individuals(93%) willingness to use
      prescription medication. Three possibly dangerous CAM were identified.
      CONCLUSIONS: Clinicians should be aware of patient-generated causal models of
      asthma and use of CAM in this population. Discussing patients' desire for an
      integrated approach to asthma management and involving social networks are 2
      strategies that may enhance patient provider partnerships and treatment fidelity.

PMID- 16995891
TI  - Brief report: graduated compression stocking thromboprophylaxis for elderly
      inpatients: a propensity analysis.
AB  - BACKGROUND: Graduated compression stockings (GCS) are often used for deep vein
      thrombosis prophylaxis in nonsurgical patients, although evidence on their
      effectiveness is lacking in this setting. OBJECTIVE: To determine whether
      prophylaxis with GCS is associated with a decrease in the rate of deep vein
      thrombosis in nonsurgical elderly patients. METHODS: Using original data from 2
      multicenter nonrandomized studies, we performed multivariable and propensity
      score analyses to determine whether prophylaxis with GCS reduced the rate of deep
      vein thrombosis among 1,310 postacute care patients 65 years or older. The
      primary outcome was proximal deep vein thrombosis detected by routine compression
      ultrasonography performed by registered vascular physicians. RESULTS: Proximal
      deep vein thrombosis was found in 5.7% (21/371) of the GCS users and in 5.2%
      (49/939) of the GCS nonusers (odds ratio [OR], 1.09; 95% confidence interval
      [CI], 0.64-1.84). Although adjusting for propensity score eliminated all
      differences in baseline characteristics between users and nonusers, the OR for
      proximal deep vein thrombosis associated with GCS remained nonsignificant in
      propensity-stratified (adjusted OR, 1.11; 95% CI, 0.59-2.10) and propensity
      matched (conditional OR, 0.92; 95% CI, 0.42-2.02) analysis. Similar figures were
      observed for distal and any deep vein thrombosis. The rates of deep vein
      thrombosis did not differ according to the length of stockings. CONCLUSIONS:
      Prophylaxis with GCS is not associated with a lower rate of deep vein thrombosis
      in nonsurgical elderly patients in routine practice. Randomized studies are
      needed to assess the efficacy of GCS when properly used in this setting.

PMID- 16995892
TI  - When do older adults turn to the internet for health information? Findings from
      the Wisconsin Longitudinal Study.
AB  - BACKGROUND: Understanding how and when patients use nonphysician sources of
      health information is important to facilitate shared decision making within
      provider outpatient visits. However, little is known about which older adults
      seek health information on the internet or when. OBJECTIVE: To determine how
      patient characteristics are related to seeking health information online and to
      the timing of these searches in relation to doctor visits. PARTICIPANTS: Six
      thousand two hundred and seventy-nine respondents (aged 63 to 66 years) who
      completed the 2004 round of phone and mail surveys (70% response) as part of the
      Wisconsin Longitudinal Study Graduate Sample. MEASUREMENTS: Self-reported use of
      the internet to search for health information and timing of use. RESULTS: One
      third of respondents had searched online for information about their own health
      or health care. Half of these searched for health information unrelated to their
      last doctor visit, while 1/3 searched after a visit, and 1/6 searched before.
      Among respondents with internet access at home or work, years of education (odds
      ratio [OR]=1.09, confidence interval [CI]=1.06 to 1.13) and openness-to
      experience (OR=1.26, CI=1.16 to 1.36) were positively associated with searching
      online for health information irrespective of timing in relation to doctor
      visits. Compared with those who had never sought health information online,
      sicker individuals (especially those with cancer, OR=1.51, CI=1.14 to 1.99) were
      more likely to seek information online after a doctor visit. Attitudinal and
      personality factors were related to seeking health information online before or
      unrelated to a visit. CONCLUSIONS: There are important differences in the timing
      of online health information searches by psychological and health characteristics
      among older adults with internet access.

PMID- 16995893
TI  - A self-determination multiple risk intervention trial to improve smokers' health.
AB  - BACKGROUND: Little is known about how interventions motivate individuals to
      change multiple health risk behaviors. Self-determination theory (SDT) proposes
      that patient autonomy is an essential factor for motivating change. OBJECTIVE: An
      SDT-based intervention to enhance autonomous motivation for tobacco abstinence
      and improving cholesterol was tested. DESIGN: The Smokers' Health Study is a
      randomized multiple risk behavior change intervention trial. SETTING: Smokers
      were recruited to a tobacco treatment center. PATIENTS: A total of 1.006 adult
      smokers were recruited between 1999 and 2002 from physician offices and by
      newspaper advertisements. INTERVENTIONS: A 6-month clinical intervention (4
      contacts) to facilitate internalization of autonomy and perceived competence for
      tobacco abstinence and reduced percent calories from fat was compared with
      community care. Clinicians elicited patient perspectives and life strivings,
      provided absolute coronary artery disease risk estimates,enumerated effective
      treatment options, supported patient initiatives,minimized clinician control,
      assessed motivation for change, and developed a plan for change. OUTCOME
      MEASURES: Twelve-month prolonged tobacco abstinence, and change in percent
      calories from fat and low-density lipoprotein-cholesterol (LDL-C) from baseline
      to 18 months. RESULTS- Intention to treat analyses revealed that the intervention
      significantly increased 12-month prolonged tobacco abstinence (6.2% vs 2.4%; odds
      ratio [OR]=2.7, P=.01, number needed to treat [NNT] =26), and reduced LDL-C (-8.9
      vs -4.1 mg/dL; P=.05). There was no effect on percent calories from fat.
      CONCLUSIONS: An intervention focused on supporting smokers'autonomy was effective
      in increasing prolonged tobacco abstinence and lowering LDL-C. Clinical
      interventions for behavior change may be improved by increasing patient autonomy
      and perceived competence.

PMID- 16995894
TI  - Brief report: development of a prescription medication information webliography
      for consumers.
AB  - BACKGROUND: Websites offering drug information vary in coverage and quality, and
      most health care consumers are poorly equipped to assess the quality of internet
      medication information. OBJECTIVE: To establish a webliography of recommended
      prescription medication information websites for health care consumers and
      providers. DESIGN AND METHODS: Drug information websites were systematically
      identified based on recommendations from health professionals and text-word
      searches of MEDLINE and Google. The resulting sample of websites was evaluated in
      a 2-step process. Candidate websites were first screened using
      inclusion/exclusion criteria representing minimum information requirements.
      Websites that passed the inclusion/exclusion criteria were then rated on 16
      quality criteria using a 5-point scale by 3 trained judges. Website ratings were
      averaged, then multiplied by the corresponding importance weight of each
      criterion and summed to generate a total score. Websites with the highest total
      scores were included in the webliography. RESULTS: Ten websites were selected for
      inclusion in the webliography. The 3 highest-scoring websites were Anthem Blue
      Cross and Blue Shield (http://home.anthemhealth.com/topic/drugcenter), U.S.
      National Library of Medicine
      (https://www.nlm.nih.gov/medlineplus/druginformation.html), and Healthvision
      (http://www.yourhealthinformation.com/library/healthguide/en
      us/drugguide/default.htm). CONCLUSION: Medication information websites vary
      widely in quality and content. The online webliography is a valuable and easily
      accessed tool that can be recommended by health care professionals to patients
      who request referral to reliable websites.

PMID- 16995895
TI  - Transcriptional regulation of the Pseudomonas aeruginosa type III secretion
      system.
AB  - Type III secretion systems (T3SS) function by translocating effector proteins
      into eukaryotic host cells and are important for the virulence of many Gram
      negative bacterial pathogens. Although the secretion and translocation
      machineries are highly conserved between different species, each pathogen
      translocates a unique set of effectors that subvert normal host cell physiology
      to promote pathogenesis. The uniqueness of each pathogen is further reflected in
      the diversity of mechanisms used to regulate T3SS gene expression. Pseudomonas
      aeruginosa utilizes a complex set of signalling pathways to modulate T3SS
      expression in response to extracellular and intracellular cues. Whereas some
      pathways are dedicated solely to regulating the T3SS, others co-ordinately
      regulate expression of the T3SS with multiple virulence functions on a global
      scale. Emerging regulatory themes include coupling of T3SS transcription with
      type III secretory activity, global regulatory control through modulation of cAMP
      biosynthesis, repression by a variety of stresses, involvement of multiple two
      component regulatory systems, and an inverse relationship between T3SS expression
      and multicellular behaviour. Factors controlling activation of T3SS expression
      likely contribute to the environmental survival of the organism and to the
      pathogenesis of acute P. aeruginosa infections. Conversely, active repression of
      the T3SS might contribute to the persistence of chronic infections.

PMID- 16995896
TI  - Differentiation between electron transport sensing and proton motive force
      sensing by the Aer and Tsr receptors for aerotaxis.
AB  - Aerotaxis (oxygen-seeking) behaviour in Escherichia coli is a response to changes
      in the electron transport system and not oxygen per se. Because changes in proton
      motive force (PMF) are coupled to respiratory electron transport, it is difficult
      to differentiate between PMF, electron transport or redox, all primary candidates
      for the signal sensed by the aerotaxis receptors, Aer and Tsr. We constructed
      electron transport mutants that produced different respiratory H+/e-
      stoichiometries. These strains expressed binary combinations of one NADH
      dehydrogenase and one quinol oxidase. We then introduced either an aer or tsr
      mutation into each mutant to create two sets of electron transport mutants. In
      vivo H+/e- ratios for strains grown in glycerol medium ranged from 1.46+/-0.18
      3.04+/-0.47, but rates of respiration and growth were similar. The PMF jump in
      response to oxygen was proportional to the H+/e- ratio in each set of mutants
      (r2=0.986-0.996). The length of Tsr-mediated aerotaxis responses increased with
      the PMF jump (r2=0.988), but Aer-mediated responses did not correlate with either
      PMF changes (r2=0.297) or the rate of electron transport (r2=0.066). Aer-mediated
      responses were linked to NADH dehydrogenase I, although there was no absolute
      requirement. The data indicate that Tsr responds to changes in PMF, but strong
      Aer responses to oxygen are associated with redox changes in NADH dehydrogenase
      I.

PMID- 16995897
TI  - Positive regulation of Bacillus subtilis ackA by CodY and CcpA: establishing a
      potential hierarchy in carbon flow.
AB  - Conversion of pyruvate to acetate via the phosphotransacetylase-acetate kinase
      pathway generates ATP and is a major overflow pathway under conditions of carbon
      and nitrogen excess. In Bacillus subtilis, this pathway is positively regulated
      by CcpA, a global regulator of carbon metabolism genes. Transcription of the
      acetate kinase gene (ackA) proved to be activated as well by a second global
      regulatory protein, CodY. Expression of an ackA-lacZ fusion was reduced in a codY
      mutant strain. CodY was found to bind in vitro to two sites in the ackA promoter
      region and to stimulate ackA transcription in a run-off transcription assay. This
      is the first known case of direct positive regulation by CodY. CodY and CcpA were
      found to bind to neighbouring sites and their effects were additive both in vivo
      and in vitro. Surprisingly, positive regulation by CodY, unlike repression,
      responded primarily to only one type of effector molecule. That is, branched
      chain amino acids (BCAAs) served as more potent co-activators of CodY-dependent
      ackA transcription than did GTP. Given the roles of CcpA and CodY in regulating
      genes whose products determine the metabolic fate of pyruvate, these two proteins
      may act together to mediate a hierarchical conversion of pyruvate to its many
      potential products.

PMID- 16995898
TI  - Thiosulphate oxidation in the phototrophic sulphur bacterium Allochromatium
      vinosum.
AB  - Two different pathways for thiosulphate oxidation are present in the purple
      sulphur bacterium Allochromatium vinosum: oxidation to tetrathionate and complete
      oxidation to sulphate with obligatory formation of sulphur globules as
      intermediates. The tetrathionate:sulphate ratio is strongly pH-dependent with
      tetrathionate formation being preferred under acidic conditions. Thiosulphate
      dehydrogenase, a constitutively expressed monomeric 30 kDa c-type cytochrome with
      a pH optimum at pH 4.2 catalyses tetrathionate formation. A periplasmic
      thiosulphate-oxidizing multienzyme complex (Sox) has been described to be
      responsible for formation of sulphate from thiosulphate in chemotrophic and
      phototrophic sulphur oxidizers that do not form sulphur deposits. In the sulphur
      storing A. vinosum we identified five sox genes in two independent loci (soxBXA
      and soxYZ). For SoxA a thiosulphate-dependent induction of expression, above a
      low constitutive level, was observed. Three sox-encoded proteins were purified:
      the heterodimeric c-type cytochrome SoxXA, the monomeric SoxB and the
      heterodimeric SoxYZ. Gene inactivation and complementation experiments proved
      these proteins to be indispensable for thiosulphate oxidation to sulphate. The
      intermediary formation of sulphur globules in A. vinosum appears to be related to
      the lack of soxCD genes, the products of which are proposed to oxidize SoxY-bound
      sulphane sulphur. In their absence the latter is instead transferred to growing
      sulphur globules.

PMID- 16995899
TI  - An Arabidopsis chloroplast-targeted Hsp101 homologue, APG6, has an essential role
      in chloroplast development as well as heat-stress response.
AB  - Analysis of albino or pale-green (apg) mutants is important for identifying
      nuclear genes responsible for chloroplast development and pigment synthesis. We
      have identified 38 apg mutants by screening 11 000 Arabidopsis Ds-tagged lines.
      One mutant, apg6, contains a Ds insertion in a gene encoding APG6 (ClpB3), a
      homologue of the heat-shock protein Hsp101 (ClpB1). We isolated somatic
      revertants and identified two Ds-tagged and one T-DNA-tagged mutant alleles of
      apg6. All three alleles gave the same pale-green phenotype. These results suggest
      that APG6 is important for chloroplast development. The APG6 protein contains a
      transit peptide and is localized in chloroplasts. The plastids of apg6 pale-green
      cells were smaller than those of the wild type, and contained undeveloped
      thylakoid membranes. APG6 mRNA accumulated in response to heat shock in various
      organs, but not in response to other abiotic stresses. Under normal conditions,
      APG6 is constitutively expressed in the root tips, the organ boundary region, the
      reproductive tissues of mature plants where plastids exist as proplastids, and
      slightly in the stems and leaves. In addition, constitutive overexpression of
      APG6 in transgenic plants inhibited chloroplast development and resulted in a
      mild pale-green phenotype. The amounts of chloroplast proteins related to
      photosynthesis were markedly decreased in apg6 mutants. These results suggest
      that APG6 functions as a molecular chaperone involved in plastid differentiation
      mediating internal thylakoid membrane formation and conferring thermotolerance to
      chloroplasts during heat stress. The APG6 protein is not only involved in heat
      stress response in chloroplasts, but is also essential for chloroplast
      development.

PMID- 16995900
TI  - The glucosyltransferase UGT72E2 is responsible for monolignol 4-O-glucoside
      production in Arabidopsis thaliana.
AB  - The phenylpropanoid pathway in plants leads to the synthesis of a wide range of
      soluble secondary metabolites, many of which accumulate as glycosides. In
      Arabidopsis, a small cluster of three closely related genes, UGT72E1-E3, encode
      glycosyltransferases shown to glucosylate several phenylpropanoids in vitro,
      including monolignols, hydroxycinnamic acids and hydroxycinnamic aldehydes. The
      role of these genes in planta has now been investigated through genetically
      downregulating the expression of individual genes or silencing the entire
      cluster. Analysis of these transgenic Arabidopsis plants showed that the levels
      of coniferyl and sinapyl alcohol 4-O-glucosides that accumulate in light-grown
      roots were significantly reduced. A 50% reduction in both glucosides was observed
      in plants in which UGT72E2 was downregulated, whereas silencing the three genes
      led to a 90% reduction, suggesting some redundancy of function within the
      cluster. The gene encoding UGT72E2 was constitutively overexpressed in transgenic
      Arabidopsis to determine whether increased glucosylation of monolignols could
      influence flux through the soluble phenylpropanoid pathway. Elevated expression
      of UGT72E2 led to increased accumulation of monolignol glucosides in root tissues
      and also the appearance of these glucosides in leaves. In particular, coniferyl
      alcohol 4-O-glucoside accumulated to massive amounts (10 micromol g(-1) FW) in
      root tissues of these plants. Increased glucosylation of other phenylpropanoids
      also occurred in plants overexpressing this glycosyltransferase. Significantly
      changing the pattern of glycosides in the leaves also led to a pronounced change
      in accumulation of the hydroxycinnamic ester sinapoyl malate. The data
      demonstrate the plasticity of phenylpropanoid metabolism and the important role
      that glucosylation of secondary metabolites can play in cellular homeostasis.

PMID- 16995901
TI  - Molecular karyotyping and aneuploidy detection in Arabidopsis thaliana using
      quantitative fluorescent polymerase chain reaction.
AB  - Certain cellular processes are sensitive to changes in gene dosage. Aneuploidy is
      deleterious because of an imbalance of gene dosage on a chromosomal scale.
      Identification, classification and characterization of aneuploidy are therefore
      important for molecular, population and medical genetics and for a deeper
      understanding of the mechanisms underlying dosage sensitivity. Notwithstanding
      recent progress in genomic technologies, limited means are available for
      detecting and classifying changes in chromosome dose. The development of an
      inexpensive and scalable karyotyping method would allow rapid detection and
      characterization of both simple and complex aneuploid types. In addition to the
      problem of karyotyping, genomic and molecular genetic studies of aneuploids and
      polyploids are complicated by multiple heterozygous combinations possible at loci
      present in more than two copies. Quantitative scoring of allele genotypes would
      enable large-scale population genetic experiments in polyploids, and permit
      genetic analyses on bulked populations in diploid species. Here, we demonstrate
      that quantitative fluorescent-polymerase chain reaction (QF-PCR) can be used to
      simultaneously genotype and karyotype aneuploid and polyploid Arabidopsis
      thaliana. Comparison of QF-PCR with flow cytometric determination of nuclear DNA
      content indicated near perfect agreement between the methods, but complete
      karyotype resolution was only possible using QF-PCR. A complex karyotype,
      determined by QF-PCR, was validated by comparative genomic hybridization to
      microarrays. Finally, we screened the progeny of tetraploid individuals and found
      that more than 25% were aneuploid and that our artificially induced tetraploid
      strain produced fewer aneuploid individuals than a tetraploid strain isolated
      from nature.

PMID- 16995902
TI  - Preconditioning ischemia attenuates molecular indices of platelet activation
      aggregation.
AB  - BACKGROUND: Previous studies have shown that ischemic preconditioning (PC) not
      only limits infarct size, but also improves arterial patency in models of
      recurrent thrombosis. We hypothesize that this enhanced patency is presumably
      because of a PC-induced attenuation of platelet-mediated thrombosis. However,
      there is, at present, no direct evidence that PC acts on the platelets per se and
      favorably down-regulates platelet reactivity. OBJECTIVES: Our goal was to test
      the concept that PC ischemia attenuates molecular indices of platelet activation
      aggregation. METHODS: Anesthetized dogs were randomly assigned to receive 10 min
      of PC ischemia followed by 10 min of reperfusion or a time-matched control
      period. Spontaneous recurrent coronary thrombosis was then initiated in all dogs
      by injury + stenosis of the left anterior descending coronary artery. Coronary
      flow was monitored for 3 h poststenosis, and molecular indices of platelet
      activation-aggregation were quantified by whole blood flow cytometry. RESULTS:
      Coronary patency was, as expected, better-maintained following injury + stenosis
      in the PC group vs. controls (53% +/- 5%* vs. 23% +/- 5% of baseline flow,
      respectively; *P < 0.05). Moreover, PC was accompanied by: (i) a significant down
      regulation of platelet-fibrinogen binding and formation of neutrophil-platelet
      aggregates (112% +/- 14%* vs. 177% +/- 21% and 107% +/- 8%* vs. 155% +/- 19% of
      baseline values in PC vs. control groups); and (ii) a trend towards a reduction
      in platelet P-selectin expression (148% +/- 12% vs. 190% +/- 21% of baseline; *P
      < 0.05 and P = 0.09 vs. control). CONCLUSION: These data provide novel, direct
      evidence in support of the concept that ischemic PC attenuates molecular indices
      of platelet activation-aggregation.

PMID- 16995903
TI  - Differential regulation of protein S expression in hepatocytes and sinusoidal
      endothelial cells in rats with cirrhosis.
AB  - BACKGROUND: Liver dysfunction caused by intrasinusoidal microthrombi is
      frequently observed in patients with cirrhosis after hepatectomy, but the
      mechanistic pathway remains unknown. OBJECTIVE: In the present study, we
      evaluated the expression of protein S (PS) in hepatocytes and sinusoidal
      endothelial cells (SECs) from rats with dimethylnitrosoamine-induced cirrhosis
      before and after hepatectomy. RESULTS: The plasma level of PS antigen was
      significantly decreased in cirrhotic rats as compared to control rats treated
      with vehicle. PS expression was significantly decreased in hepatocytes isolated
      from cirrhotic rats as compared to controls. In contrast, PS expression was
      significantly increased in SECs isolated from rats with cirrhosis as compared to
      controls. Interleukin-6 (IL-6) upregulated the expression of PS in hepatocytes,
      and tumor necrosis factor-alpha (TNF-alpha) decreased its expression in SECs from
      both cirrhotic and normal rats. The production of IL-6 and TNF-alpha by Kupffer
      cells and SECs was decreased in rats with cirrhosis as compared to controls.
      After hepatectomy, microthrombus formation was markedly enhanced in sinusoids
      from rats with cirrhosis, and the plasma levels of IL-6 and TNF-alpha were
      significantly increased in rats with cirrhosis as compared to controls.
      Furthermore, PS production in SECs was decreased, whereas that in hepatocytes was
      significantly increased in cirrhotic rats as compared to controls. CONCLUSIONS:
      These findings suggest that PS expression is differently regulated in hepatocytes
      and SECs of rats with cirrhosis before and after hepatectomy, that the expression
      of PS is regulated by locally released inflammatory cytokines, and that decreased
      expression of PS in SECs may cause liver microthrombus formation, which is
      frequently observed in patients with cirrhosis after hepatectomy.

PMID- 16995904
TI  - Early growth response transcription factor EGR-1 regulates Galphaq gene in
      megakaryocytic cells.
AB  - BACKGROUND: Galphaq (Gene GNAQ) plays a major role in platelet signal
      transduction but little is known regarding its transcriptional regulation.
      OBJECTIVES: We studied Galphaq promoter activity using luciferase reporter gene
      assays in human erythroleukemia (HEL) cells treated with phorbol 12-myristate 13
      acetate (PMA) for 24 h to induce megakaryocytic transformation. METHODS AND
      RESULTS: PMA-treated HEL cells showed enhanced Galphaq expression. Reporter
      (luciferase) gene studies on 5' upstream construct (up to -116 bp from ATG)
      revealed a negative regulatory site at -238/-202 and two positive sites at -203/
      138 and -1116/-731. The positive regulatory region -203/-138 contained
      overlapping Sp1/AP-2/EGR-1 consensus sites. Gel shift studies on Galphaq
      oligonucleotides 1 (-203/-175) and 2 (-174/-152) using HEL cell extracts
      demonstrated protein binding that was due to early growth response factor EGR-1
      at two sites. Mutations in either EGR-1 site markedly decreased the gene
      activity, indicating functional relevance. Mutation of consensus E-Box motif (
      185/-180) had no effect. Reduction in the expression of endogenous EGR-1 with
      antisense oligonucleotide to EGR-1 inhibited PMA-induced Galphaq transcription.
      Correspondingly, Egr-1 deficient mouse platelets also showed approximately 50%
      reduction in the Galphaq expression relative to wild-type platelets. CONCLUSIONS:
      These studies suggest that Galphaq gene is regulated during PMA-induced
      megakaryocytic differentiation by EGR-1, an early growth response transcription
      factor that regulates a wide array of genes and plays a major role in diverse
      activities, including cell proliferation, differentiation and apoptosis, and in
      vascular response to injury and atherosclerosis.

PMID- 16995906
TI  - Glomeraceae and Gigasporaceae differ in their ability to form hyphal networks.

PMID- 16995907
TI  - Variability matters: towards a perspective on the influence of precipitation on
      terrestrial ecosystems. Effects of precipitation change on ecosystems (EPRECOT)-
      a Terrestrial Ecosystem Response to Atmospheric and Climatic Change (TERACC) and
      European Commission sponsored precipitation workshop, Elsinore, Denmark, May
      2006.

PMID- 16995908
TI  - First encounters--deployment of defence-related natural products by plants.
AB  - Plant-derived natural products have important functions in ecological
      interactions. In some cases these compounds are deployed to sites of pathogen
      challenge by vesicle-mediated trafficking. Polar vesicle trafficking of natural
      products, proteins and other, as yet uncharacterized, cargo is emerging as a
      common theme in investigations of diverse disease resistance mechanisms in
      plants. Root-derived natural products can have marked effects on interactions
      between plants and soilborne organisms, for example by serving as signals for
      initiation of symbioses with rhizobia and mycorrhizal fungi. They may also
      contribute to competitiveness of invasive plant species by inhibiting the growth
      of neighbouring plants (allelopathy). Very little is known about the mechanisms
      of release of natural products from aerial plant parts or from roots, although
      there are likely to be commonalities in these processes. There is increasing
      evidence to indicate that pathogens and symbionts can manipulate plant
      endomembrane systems to suppress host defence responses and facilitate
      accommodation within plant cells. The relationship between secretory processes
      and plant interactions forms the focus of this review, which brings together
      different aspects of the deployment of defence-related natural products by
      plants.

PMID- 16995909
TI  - Application of electron tomography to fungal ultrastructure studies.
AB  - Access to structural information at the nanoscale enables fundamental insights
      into many complex biological systems. The development of the transmission
      electron microscope (TEM) has vastly increased our understanding of multiple
      biological systems. However, when attempting to visualize and understand the
      organizational and functional complexities that are typical of cells and tissues,
      the standard 2-D analyses that TEM affords often fall short. In recent years,
      high-resolution electron tomography methods, coupled with advances in specimen
      preparation and instrumentation and computational speed, have resulted in a
      revolution in the biological sciences. Electron tomography is analogous to
      medical computerized axial tomography (CAT-scan imaging) except at a far finer
      scale. It utilizes the TEM to assemble multiple projections of an object which
      are then combined for 3-D analyses. For biological specimens, tomography enables
      the highest 3-D resolution (5 nm spatial resolution) of internal structures in
      relatively thick slices of material (0.2-0.4 microm) without requiring the
      collection and alignment of large numbers of thin serial sections. Thus accurate
      and revealing 3-D reconstructions of complex cytoplasmic entities and
      architecture can be obtained. Electron tomography is now being applied to a
      variety of biological questions with great success. This review gives a brief
      introduction into cryopreservation and electron tomography relative to aspects of
      cytoplasmic organization in the hyphal tip of Aspergillus nidulans.

PMID- 16995910
TI  - Production of reactive oxygen species and reactive nitrogen species by angiosperm
      stigmas and pollen: potential signalling crosstalk?
AB  - Angiosperm stigmas exhibit high levels of peroxidase activity when receptive to
      pollen. To explore possible function(s) of this peroxidase activity we
      investigated amounts of reactive oxygen species (ROS), particularly hydrogen
      peroxide, in stigmas and pollen. Because nitric oxide (NO) was recently
      implicated in pollen tube growth, we also investigated amounts of NO in pollen
      and stigmas. Reactive oxygen species accumulation was assessed with confocal
      microscopy and light microscopy using ROS probes DCFH2-DA and TMB, respectively.
      NO was assayed using the NO probe DAF-2DA and confocal microscopy. Stigmas from
      various different angiosperms were found to accumulate ROS, predominantly H2O2,
      constitutively. In Senecio squalidus and Arabidopsis thaliana high amounts of
      ROS/H2O2 were localized to stigmatic papillae. ROS/H2O2 amounts appeared reduced
      in stigmatic papillae to which pollen grains had adhered. S. squalidus and A.
      thaliana pollen produced relatively high amounts of NO compared with stigmas;
      treating stigmas with NO resulted in reduced amounts of stigmatic ROS/H2O2.
      Constitutive accumulation of ROS/H2O2 appears to be a feature of angiosperm
      stigmas. This novel finding is discussed in terms of a possible role for
      stigmatic ROS/H2O2 and pollen-derived NO in pollen-stigma interactions and
      defence.

PMID- 16995911
TI  - Transcription of ethylene perception and biosynthesis genes is altered by
      putrescine, spermidine and aminoethoxyvinylglycine (AVG) during ripening in peach
      fruit (Prunus persica).
AB  - The time course of ethylene biosynthesis and perception was investigated in
      ripening peach fruit (Prunus persica) following treatments with the polyamines
      putrescine (Pu) and spermidine (Sd), and with aminoethoxyvinylglycine (AVG).
      Fruit treatments were performed in planta. Ethylene production was measured by
      gas chromatography, and polyamine content by high-performance liquid
      chromatography; expression analyses were performed by Northern blot or real-time
      polymerase chain reaction. Differential increases in the endogenous polyamine
      pool in the epicarp and mesocarp were induced by treatments; in both cases,
      ethylene production, fruit softening and abscission were greatly inhibited. The
      rise in 1-aminocyclopropane-1-carboxylate oxidase (PpACO1) mRNA was counteracted
      and delayed in polyamine-treated fruit, whereas transcript abundance of ethylene
      receptors PpETR1 (ethylene receptor 1) and PpERS1 (ethylene sensor 1) was
      enhanced at harvest. Transcript abundance of arginine decarboxylase (ADC) and S
      adenosylmethionine decarboxylase (SAMDC) was transiently reduced in both the
      epicarp and mesocarp. AVG, here taken as a positive control, exerted highly
      comparable effects to those of Pu and Sd. Thus, in peach fruit, increasing the
      endogenous polyamine pool in the epicarp or in the mesocarp strongly interfered,
      both at a biochemical and at a biomolecular level, with the temporal evolution of
      the ripening syndrome.

PMID- 16995912
TI  - Growth and senescence of Medicago truncatula cultured cells are associated with
      characteristic mitochondrial morphology.
AB  - Here mitochondrial morphology and dynamics were investigated in Medicago
      truncatula cell-suspension cultures during growth and senescence. Cell biology
      techniques were used to measure cell growth and death in culture. Mitochondrial
      morphology was investigated in vivo using a membrane potential sensor probe
      coupled with confocal microscopy. Expression of a senescence-associated gene
      (MtSAG) was evaluated in different cell-growth phases. Mitochondria appeared as
      numerous, punctuate organelles in cells at the beginning of the subculture cycle,
      while interconnected networks were observed in actively growing cells. In
      senescent cells, giant mitochondria were associated with dying cells. The release
      of cytochrome c from mitochondria was detected in different growth phases of
      cultured cells. Studies on plant cell cultures allowed us to identify
      physiological and molecular markers of senescence and cell death, and to
      associate distinct mitochondrial morphology with cells under different
      physiological conditions.

PMID- 16995913
TI  - Assessment of plants from the Brassicaceae family as genetic models for the study
      of nickel and zinc hyperaccumulation.
AB  - We report on the second phase of a programme to select a relative of Arabidopsis
      thaliana for use in large-scale molecular genetic studies of nickel (Ni) and zinc
      (Zn) hyperaccumulation. We also report on the relatedness among Thlaspi
      caerulescens accessions and the utility of using O-acetyl-L-serine as a marker
      for Ni and Zn hyperaccumulation potential. Twenty-seven new accessions of metal
      accumulating species collected in the Czech Republic, France, Greece, Italy,
      Slovenia and the USA during Spring-Summer 2002 were evaluated. The criteria
      established for selection were hyperaccumulation of metals (Ni and Zn); compact
      growth habit; reasonable time to flowering; production of > or = 1000 seeds per
      plant; self-fertility; compact diploid genome; high sequence similarity to A.
      thaliana; > or = 0.1% transformation efficiency with easy selection. We conclude
      that the best candidate identified in the first phase was the best candidate
      overall: T. caerulescens accession St Felix de Pallieres.

PMID- 16995914
TI  - Characterization of cadmium uptake, translocation and storage in near-isogenic
      lines of durum wheat that differ in grain cadmium concentration.
AB  - Here we examined several physiological properties of two near-isogenic lines of
      durum wheat (Triticum turgidum var. durum) that differ in grain cadmium
      accumulation, to identify the function of a gene locus that confers differential
      grain Cd concentrations. Time- and concentration-dependent uptake and
      translocation studies using 109Cd were conducted on nutrient solution-grown
      seedlings. Root extracts were analysed by inductively coupled plasma emission
      spectrometry, gel filtration and capillary electrophoresis to determine the
      interaction between Cd and phytochelatins (PCs) in storage of Cd in roots. The
      two isolines did not differ in time- or concentration-dependent root Cd uptake,
      but the low grain-Cd-accumulating isoline showed decreased movement of Cd from
      roots to shoots. All buffer-soluble Cd extracted from roots of both isolines was
      in the form of a low-molecular-weight PC-containing complex. The data suggest
      that PC synthesis is not a limiting factor in the differential storage of Cd in
      roots, and that movement of Cd through the root and into the transpiration stream
      may be the cause of differential Cd partitioning in the two isolines.

PMID- 16995915
TI  - Winter down-regulation of intrinsic photosynthetic capacity coupled with up
      regulation of Elip-like proteins and persistent energy dissipation in a subalpine
      forest.
AB  - Overwintering, sun-exposed and photosynthetically inactive evergreens require
      powerful photoprotection. The goal of this study was to seasonally characterize
      photosynthesis and key proteins/components involved in electron transport and
      photoprotection. Maximal photosystem II (PSII) efficiency and photosynthetic
      capacity, amounts of zeaxanthin (Z), antheraxanthin (A), pheophytin and proteins
      (oxygen-evolving 33 kDa protein (OEC), PSII core protein D1 and subunit S (PsbS)
      protein, and members of the early light-inducible protein (Elip) family) were
      assessed in five conifer species at high altitude and in ponderosa pine (Pinus
      ponderosa) at moderate altitude during summer and winter. Relative to summer,
      winter down-regulation of photosynthetic capacity and loss of PSII efficiency at
      the high-altitude sites were paralleled by decreases in OEC, D1, and pheophytin;
      massive nocturnal retention of (Z + A) and up-regulation of two to four proteins
      cross-reactive with anti-Elip antibodies; and no change in PsbS amount. By
      contrast, ponderosa pine at moderate altitude exhibited no down-regulation of
      photosynthetic capacity, smaller depressions in PSII efficiency, and less up
      regulation of Elip family members. These results support a function for members
      of the Elip family in the acclimation of sun-exposed needles that down-regulate
      photosynthesis during winter. A possible role in sustained photoprotection is
      considered.

PMID- 16995916
TI  - Photosynthetic capacity and light harvesting efficiency during the winter-to
      spring transition in subalpine conifers.
AB  - Some coniferous forest ecosystems undergo complete photosynthetic down-regulation
      in winter. The present study examined the influence of several environmental
      parameters on intrinsic, needle-level photosynthesis and photoprotection during
      the spring reactivation of photosynthesis in subalpine conifers. Maximal
      photosystem II (PSII) efficiency, photosynthetic capacity, and amounts of
      zeaxanthin and early light-inducible protein (Elip) family members were assessed
      in three subalpine conifer species over 3 years, and intensively during the 2003
      winter-to-spring transition. During summers, maximal PSII efficiency remained
      high while intrinsic photosynthetic capacity varied depending on precipitation.
      During winters and the winter-to-spring transition, photosynthetic capacity and
      PSII efficiency were highly correlated and (during the spring transition)
      strongly influenced by air and soil temperature and liquid water availability.
      Decreases in the amount of Elip family members from winter through spring
      paralleled disengagement of sustained zeaxanthin-dependent photoprotection,
      although one of four anti-Elip antibody-reactive bands increased during spring.
      Intrinsic photosynthetic capacity and maximal PSII efficiency were highly
      responsive to day-to-day environmental changes during spring, indicating that
      multiple environmental signals are integrated to orchestrate the reactivation of
      photosynthesis from the inactive winter state to the active summer state.

PMID- 16995917
TI  - Does shade improve light interception efficiency? A comparison among seedlings
      from shade-tolerant and -intolerant temperate deciduous tree species.
AB  - Here, we tested two hypotheses: shading increases light interception efficiency
      (LIE) of broadleaved tree seedlings, and shade-tolerant species exhibit larger
      LIEs than do shade-intolerant ones. The impact of seedling size was taken into
      account to detect potential size-independent effects on LIE. LIE was defined as
      the ratio of mean light intercepted by leaves to light intercepted by a
      horizontal surface of equal area. Seedlings from five species differing in shade
      tolerance (Acer saccharum, Betula alleghaniensis, A. pseudoplatanus, B. pendula,
      Fagus sylvatica) were grown under neutral shading nets providing 36, 16 and 4% of
      external irradiance. Seedlings (1- and 2-year-old) were three-dimensionally
      digitized, allowing calculation of LIE. Shading induced dramatic reduction in
      total leaf area, which was lowest in shade-tolerant species in all irradiance
      regimes. Irradiance reduced LIE through increasing leaf overlap with increasing
      leaf area. There was very little evidence of significant size-independent
      plasticity of LIE. No relationship was found between the known shade tolerance of
      species and LIE at equivalent size and irradiance.

PMID- 16995918
TI  - Attenuated total reflectance spectroscopy of plant leaves: a tool for ecological
      and botanical studies.
AB  - Attenuated total reflectance (ATR) spectra of plant leaves display complex
      absorption features related to organic constituents of leaf surfaces. The spectra
      can be recorded rapidly, both in the field and in the laboratory, without special
      sample preparation. This paper explores sources of ATR spectral variation in
      leaves, including compositional, positional and temporal variations.
      Interspecific variations are also examined, including the use of ATR spectra as a
      tool for species identification. Positional spectral variations generally
      reflected the abundance of cutin and the epicuticular wax thickness and
      composition. For example, leaves exposed to full sunlight commonly showed more
      prominent cutin- and wax-related absorption features compared with shaded leaves.
      Adaxial vs. abaxial leaf surfaces displayed spectral variations reflecting
      differences in trichome abundance and wax composition. Mature vs. young leaves
      showed changes in absorption band position and intensity related to cutin,
      polysaccharide, and possibly amorphous silica development on and near the leaf
      surfaces. Provided that similar samples are compared (e.g. adaxial surfaces of
      mature, sun-exposed leaves) same-species individuals display practically
      identical ATR spectra. Using spectral matching procedures to analyze an ATR
      database containing 117 individuals, including 32 different tree species, 83% of
      the individuals were correctly identified.

PMID- 16995919
TI  - Canopy CO2 enrichment permits tracing the fate of recently assimilated carbon in
      a mature deciduous forest.
AB  - How rapidly newly assimilated carbon (C) is invested into recalcitrant structures
      of forests, and how closely C pools and fluxes are tied to photosynthesis, is
      largely unknown. A crane and a purpose-built free-air CO2 enrichment (FACE)
      system permitted us to label the canopy of a mature deciduous forest with 13C
      depleted CO2 for 4 yr and continuously trace the flow of recent C through the
      forest without disturbance. Potted C4 grasses in the canopy ('isometers') served
      as a reference for the C-isotope input signal. After four growing seasons, leaves
      were completely labelled, while newly formed wood (tree rings) still contained 9%
      old C. Distinct labels were found in fine roots (38%) and sporocarps of
      mycorrhizal fungi (62%). Soil particles attached to fine roots contained 9% new
      C, whereas no measurable signal was detected in bulk soil. Soil-air CO2 consisted
      of 35% new C, indicating that considerable amounts of assimilates were rapidly
      returned back to the atmosphere. These data illustrate a relatively slow dilution
      of old mobile C pools in trees, but a pronounced allocation of very recent
      assimilates to C pools of short residence times.

PMID- 16995920
TI  - Importance of short-term dynamics in carbon isotope ratios of ecosystem
      respiration (delta13C(R)) in a Mediterranean oak woodland and linkage to
      environmental factors.
AB  - Temporal dynamics in carbon isotope ratios of ecosystem respiration (delta13C(R))
      were evaluated on hourly, daily and annual timescales in a Mediterranean
      woodland. Emphasis was given to the periods of transition from wet to dry season
      and vice versa, when the system turns from a net carbon sink to a source. The
      constancy of nocturnal delta13C(R) was tested. The relationship between
      delta13C(R) (determined through Keeling plots) and environmental factors was
      evaluated through time-lag analysis. Delta13C(R) exhibited high annual variation
      (> 7). During the transition periods, delta13C(R) correlated significantly with
      factors influencing photosynthetic discrimination, soil respiration, and whole
      canopy conductance. Time-lags differed between below- and above-ground variables,
      and between seasons. A shift in regression parameters with environmental factors
      indicated seasonal differences in ecosystem responsiveness (e.g. temperature
      acclimation). Delta13C(R) exhibited substantial nocturnal enrichment (> 4) from
      dusk to dawn. These data indicate pronounced short-term dynamics in delta13C(R)
      at hourly to daily timescales and a modulated response to environmental drivers.
      Substantial short-term changes in nocturnal delta13C(R) may have important
      implications for the sampling protocols of nocturnal Keeling plots.

PMID- 16995921
TI  - Functional diversity of arbuscular mycorrhizal fungal isolates in relation to
      extraradical mycelial networks.
AB  - We investigated the functional significance of extraradical mycorrhizal networks
      produced by geographically different isolates of the arbuscular mycorrhizal
      fungal (AMF) species Glomus mosseae and Glomus intraradices. A two-dimensional
      experimental system was used to visualize and quantify intact extraradical
      mycelium (ERM) spreading from Medicago sativa roots. Growth, phosphorus (P) and
      nitrogen (N) nutrition were assessed in M. sativa plants grown in microcosms. The
      AMF isolates were characterized by differences in extent and interconnectedness
      of ERM. Phenotypic fungal variables, such as total hyphal length, hyphal density,
      hyphal length per mm of total or colonized root length, were positively
      correlated with M. sativa growth response variables, such as total shoot biomass
      and plant P content. The utilization of an experimental system in which size,
      growth rate, viability and interconnectedness of ERM extending from mycorrhizal
      roots are easily quantified under realistic conditions allows the simultaneous
      evaluation of different isolates and provides data with a predictive value for
      selection of efficient AMF.

PMID- 16995922
TI  - A test for hydrotropic behavior by roots of two coastal dune shrubs.
AB  - Root hydrotropism could be a means by which plants forage for limited and patchy
      distributions of soil water. While root hydrotropism has been induced in
      distinctly artificial conditions, it is unclear if it operates in natural
      settings. Here, we tested for this possibility in seedlings of two species of
      dune shrubs. Growth of individual roots in sand-filled observation chambers was
      monitored in response to moisture-rich patches and resultant soil water
      gradients. Chambers were designed so that roots could intercept the moisture
      gradients but not the moisture-rich patches simply through gravitropism. While up
      to 12% of the Eriogonum parvifolium roots grew into the moisture-rich patches,
      comparable root growth was observed in the control. None of the Artemisia
      californica roots grew into the patches. Thus, in a reasonable simulation of
      field conditions, we found no compelling evidence for hydrotropic root behavior
      in seedlings of these two dune shrubs. Our results leave the ecological
      significance of root hydrotropism in question.

PMID- 16995923
TI  - Frozen in time: a new method using cryo-scanning electron microscopy to visualize
      root-fungal interactions.
AB  - A new method of sample preparation for cryo-scanning electron microscopy was used
      to visualize internal infection of wheat (Triticum aestivum) roots by the
      pathogenic fungus Rhizoctonia solani AG-8. The new method retained fungal hyphae
      and root cells in situ in disintegrating root tissues, thus avoiding the
      distortions that can be introduced by conventional preparation by chemical
      fixation, dehydration and embedding. Infected roots frozen in liquid nitrogen
      were cryo-planed and etched (sublimed) at -80 degrees C for a critical length of
      time (up to 9 min) in the microscope column to reveal plant and fungal structures
      in three dimensions. Root and fungal structures were well preserved irrespective
      of infection severity. Root and hyphal cell walls were clearly seen and hyphal
      architecture within and between root cells was preserved. This rapid method
      permits three-dimensional in situ visualization of fungal invasion within roots
      and has broad application for examination of diseases caused by other
      necrotrophic fungi.

PMID- 16995927
TI  - An ethnobotanical survey of wild edible plants of Paphos and Larnaca countryside
      of Cyprus.
AB  - An ethnobotanical survey of wild edible plants of Cyprus was carried out in two
      sites, Paphos vine zone and Larnaca mixed farming zone. These are among the areas
      in Cyprus whose inhabitants subsisted primarily on pastoralism and agriculture
      and therefore still preserve the traditional knowledge on wild edible plants. The
      information was collected for three-year period, in the framework of the EU
      funded RUBIA Project. Four hundred and thirteen interviews have been administered
      to 89 informants of various ages and background categories in 29 villages of
      Paphos site, and 8 in Larnaca site. A total of 78 species were recorded.
      Ethnographic data related to vernacular names, traditional tools and recipes have
      also been recorded. A comparison of the data collected from the two sites is
      undertaken. During this ethnobotanical research it was verified that wild edibles
      play an important role in Cyprus in rural people, however, it was realized that
      the transmission of folk uses of plants decreased in the last generations. The
      research of ethnobotany should be extended to other areas of Cyprus in order not
      only to preserve the traditional knowledge related to plants but to make it
      available to future generations as well.

PMID- 16995928
TI  - Bifunctional recombinant fusion proteins for rapid detection of antibodies to
      both HIV-1 and HIV-2 in whole blood.
AB  - BACKGROUND: Availability of accurate diagnostic tests has been helpful in
      curtailing the spread of HIV infection. Among these, simple, point of care,
      inexpensive tests which require only a drop of blood from finger-prick and give
      reliable results within minutes are a must for expansion of testing services and
      for reaching mobile and marginalized populations. Such tests will not only be a
      boon for the infrastructure-starved developing and underdeveloped countries but
      will also be extremely useful in developed countries where post-testing
      compliance is a major problem. Our laboratory has been involved in developing
      reagents for heamagglutination-based rapid detection of antibodies to HIV in
      whole blood using recombinant molecules specific for either HIV-1 or HIV-2. Since
      it is not required of a screening test to differentially detect HIV and HIV-2, it
      would useful to create a single molecule capable of simultaneous detection of
      both HIV-1 and HIV-2 in a drop of blood. RESULTS: The present paper describes
      designing, high-level expression and large-scale purification of new molecules
      comprising recombinant anti-RBC Fab fused to immunodominant regions of envelope
      sequences from both gp41 of HIV-1 and gp36 of HIV-2. These immunodominant regions
      of HIV envelope contain cysteine residues, which make disulfide bond and can
      interfere with the assembly of light chain and heavy chain fragment to make Fab
      molecule in vitro. To circumvent this problem, a series of fusion proteins having
      different combinations of native and mutant envelope sequences were constructed,
      purified and evaluated for their efficacy in detecting antibodies to HIV-1 and
      HIV-2. A chimeric molecule comprising native envelope sequence of gp41 of HIV-1
      and modified envelope sequence of gp36 of HIV-2 gave good production yield and
      also detected both HIV-1 and HIV-2 samples with high sensitivity and specificity.
      CONCLUSION: The new bifunctional antibody fusion protein identified in this study
      detects both HIV-1 and HIV-2 infected samples efficiently and can be used in
      place of molecules that detect only HIV-1 or HIV-2. This will make reagent
      production more economical as only one molecule has to be produced in place of
      two molecules. Also, it will simplify the testing procedure allowing detection of
      both HIV-1 and HIV-2 infections in a single drop of blood.

PMID- 16995929
TI  - Risk of acute myocardial infarction with nonselective non-steroidal anti
      inflammatory drugs: a meta-analysis.
AB  - The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs
      (NSAIDs) is associated with increased risk of acute myocardial infarction (AMI).
      The association between the risks of AMI with nonselective NSAIDs is less clear.
      We reviewed the published evidence and assessed the risk of AMI with nonselective
      NSAIDs. We performed a meta-analysis of all studies containing data from
      population databases that compared the risk of AMI in NSAID users with that in
      non-users or remote NSAID users. The primary outcome was objectively confirmed
      AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis.
      Nonselective NSAIDs as a class was associated with increased AMI risk (relative
      AMI risk 1.19, 95% confidence interval [CI] 1.08 to 1.31). Similar findings were
      found with diclofenac (relative AMI risk 1.38, 95% CI 1.22-1.57) and ibuprofen
      (relative AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not
      observed with naproxen (relative AMI risk 0.99, 95% CI 0.88-1.11). In conclusion,
      based on current evidence, there is a general direction of effect, which suggests
      that at least some nonselective NSAIDs increase AMI risk. Analysis based on the
      limited data available for individual NSAIDs, including diclofenac and ibuprofen,
      supported this finding; however, this was not the case for naproxen. Nonselective
      NSAIDs are frequently prescribed, and so further investigation into the risk of
      AMI is warranted because the potential for harm can be substantial.

PMID- 16995930
TI  - Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ
      dysfunction.
AB  - INTRODUCTION: Multiple organ dysfunction syndrome (MODS) is a common complication
      of sepsis in mechanically ventilated patients with acute respiratory distress
      syndrome, but the links between mechanical ventilation and MODS are unclear. Our
      goal was to determine whether a minimally injurious mechanical ventilation
      strategy synergizes with low-dose endotoxemia to induce the activation of pro
      inflammatory pathways in the lungs and in the systemic circulation, resulting in
      distal organ dysfunction and/or injury. METHODS: We administered intraperitoneal
      Escherichia coli lipopolysaccharide (LPS; 1 microg/g) to C57BL/6 mice, and 14
      hours later subjected the mice to 6 hours of mechanical ventilation with tidal
      volumes of 10 ml/kg (LPS + MV). Comparison groups received ventilation but no LPS
      (MV), LPS but no ventilation (LPS), or neither LPS nor ventilation (phosphate
      buffered saline; PBS). RESULTS: Myeloperoxidase activity and the concentrations
      of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were
      significantly increased in the lungs of mice in the LPS + MV group, in comparison
      with mice in the PBS group. Interestingly, permeability changes across the
      alveolar epithelium and histological changes suggestive of lung injury were
      minimal in mice in the LPS + MV group. However, despite the minimal lung injury,
      the combination of mechanical ventilation and LPS resulted in chemical and
      histological evidence of liver and kidney injury, and this was associated with
      increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-alpha.
      CONCLUSION: Non-injurious mechanical ventilation strategies interact with
      endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and
      promote extra-pulmonary end-organ injury, even in the absence of demonstrable
      acute lung injury.

PMID- 16995931
TI  - Acute red eye and back pain as a presentation for systemic illness: case report.
AB  - BACKGROUND: Acute red eye is a common presentation in both primary and secondary
      care. Presentation in combination with other systemic symptoms can indicate
      serious underlying pathology. CASE PRESENTATION: 73-year-old lady presenting with
      endogenous endophthalmitis and thoracic discitis secondary to sub-acute bacterial
      endocarditis. CONCLUSION: Acute red eye in combination with systemic symptoms
      requires immediate investigation. If endogenous endophthalmitis is diagnosed, a
      source of sepsis should be comprehensively investigated and referral made to
      individual specialties if necessary.

PMID- 16995932
TI  - Ollier disease.
AB  - Enchondromas are common intraosseous, usually benign cartilaginous tumors, that
      develop in close proximity to growth plate cartilage. When multiple enchondromas
      are present, the condition is called enchondromatosis also known as Ollier
      disease (WHO terminology). The estimated prevalence of Ollier disease is
      1/100,000. Clinical manifestations often appear in the first decade of life.
      Ollier disease is characterized by an asymmetric distribution of cartilage
      lesions and these can be extremely variable (in terms of size, number, location,
      evolution of enchondromas, age of onset and of diagnosis, requirement for
      surgery). Clinical problems caused by enchondromas include skeletal deformities,
      limb-length discrepancy, and the potential risk for malignant change to
      chondrosarcoma. The condition in which multiple enchondromatosis is associated
      with soft tissue hemangiomas is known as Maffucci syndrome. Until now both Ollier
      disease and Maffucci syndrome have only occurred in isolated patients and not
      familial. It remains uncertain whether the disorder is caused by a single gene
      defect or by combinations of (germ-line and/or somatic) mutations. The diagnosis
      is based on clinical and conventional radiological evaluations. Histological
      analysis has a limited role and is mainly used if malignancy is suspected. There
      is no medical treatment for enchondromatosis. Surgery is indicated in case of
      complications (pathological fractures, growth defect, malignant transformation).
      The prognosis for Ollier disease is difficult to assess. As is generally the
      case, forms with an early onset appear more severe. Enchondromas in Ollier
      disease present a risk of malignant transformation of enchondromas into
      chondrosarcomas.

PMID- 16995933
TI  - Predictive factors for polypharmacy among child and adolescent psychiatry
      inpatients.
AB  - BACKGROUND: Aim was to determine the predictive factors for polypharmacy among
      inpatient children and adolescents with psychiatric disorders. METHODS: Blinded,
      case-note review of children and adolescents with ICD 10 diagnosis of psychiatric
      disorders on psychotropic medication was conducted. Data on demography, illness,
      and treatment was analyzed with univariate and multivariate techniques. RESULTS:
      Proscribing non-pharmacological interventions (OR = 4.7) and pro re nata
      medication (OR = 3.3), increased the risk of polypharmacy. Prescribing physical
      restraint reduced the risk of receiving multiple medications (OR = 0.3).
      CONCLUSION: Proscribing non-pharmacological interventions, pro re nata medication
      and physical restraints increased polypharmacy.

PMID- 16995934
TI  - Canine faecal contamination and parasitic risk in the city of Naples (southern
      Italy).
AB  - BACKGROUND: Dogs are associated with more than 60 zoonotic diseases among which,
      parasitosis and, in particular, helminthosis, can pose serious public-health
      concerns worldwide. Many canine gastrointestinal parasites eliminate their
      dispersion elements (eggs, larvae, oocysts) by the faecal route. The quantity of
      canine faeces deposited on public and private property in cities worldwide is
      both a perennial nuisance and an important health issue. Public sites such as
      playgrounds, parks, gardens, public squares and sandpits may be an important
      source of human infection. The aim of this study was to evaluate the extent of
      both canine faecal contamination in the city of Naples (southern Italy), and
      presence of canine parasitic elements, with particular regard to those which are
      potential agents of zoonosis. A regular grid of sub-areas (1 km x 700 m) was
      overlaid on the city map using a Geographical Information System (GIS). In each
      sub-area the straightest 1 km transect was drawn and digitalized on-screen in the
      GIS. Between February and May 2005 canine faeces were counted along the 1 km
      transects in 143 sub-areas, and 415 canine faecal samples were collected and
      submitted to coprological examinations. Negative binomial regression models and
      Gaussian random effects models were used to analyze the association between
      faeces count and human population density taking into account for extraPoisson
      variability. Logistic regression model was used to evaluate the association
      between positivity to parasitic elements and number of canine faeces. RESULTS:
      Out of the 143 studied sub-areas, 141 (98.6%) contained canine faeces. There was
      a strong spatial gradient with 48% of the total variability accounted by between
      neighbourhood variability; a positive association between the number of faeces
      and the human population density was found. Seventy (over 415, 16.9%) canine
      faecal samples were positive for parasitic elements. There was no association
      between positivity to parasitic elements and the number of canine faeces. Eggs of
      Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Trichuris vulpis were
      found, as well as oocysts of Isospora canis. CONCLUSION: In conclusion, the
      results of the present study, conducted using GIS both for planning and sampling
      and for evaluation and presentation of findings, showed the presence of canine
      faecal contamination in the city of Naples, and the presence of canine parasitic
      elements, some of which are potential agents of zoonosis.

PMID- 16995935
TI  - A promising method for identifying cross-cultural differences in patient
      perspective: the use of Internet-based focus groups for content validation of new
      patient reported outcome assessments.
AB  - OBJECTIVES: This proof of concept (POC) study was designed to evaluate the use of
      an Internet-based bulletin board technology to aid parallel cross-cultural
      development of thematic content for a new set of patient-reported outcome
      measures (PROs). METHODS: The POC study, conducted in Germany and the United
      States, utilized Internet Focus Groups (IFGs) to assure the validity of new PRO
      items across the two cultures--all items were designed to assess the impact of
      excess facial oil on individuals' lives. The on-line IFG activities were modeled
      after traditional face-to-face focus groups and organized by a common 'Topic'
      Guide designed with input from thought leaders in dermatology and health outcomes
      research. The two sets of IFGs were professionally moderated in the native
      language of each country. IFG moderators coded the thematic content of
      transcripts, and a frequency analysis of code endorsement was used to identify
      areas of content similarity and difference between the two countries. Based on
      this information, draft PRO items were designed and a majority (80%) of the
      original participants returned to rate the relative importance of the newly
      designed questions. FINDINGS: The use of parallel cross-cultural content analysis
      of IFG transcripts permitted identification of the major content themes in each
      country as well as exploration of the possible reasons for any observed
      differences between the countries. Results from coded frequency counts and
      transcript reviews informed the design and wording of the test questions for the
      future PRO instrument(s). Subsequent ratings of item importance also deepened our
      understanding of potential areas of cross-cultural difference, differences that
      would be explored over the course of future validation studies involving these
      PROs. CONCLUSION: The use of IFGs for cross-cultural content development received
      positive reviews from participants and was found to be both cost and time
      effective. The novel thematic coding methodology provided an empirical platform
      on which to develop culturally sensitive questionnaire content using the natural
      language of participants. Overall, the IFG responses and thematic analyses
      provided a thorough evaluation of similarities and differences in cross-cultural
      themes, which in turn acted as a sound base for the development of new PRO
      questionnaires.

PMID- 16995936
TI  - Differences in fruit and vegetable intake and determinants of intakes between
      children of Dutch origin and non-Western ethnic minority children in the
      Netherlands - a cross sectional study.
AB  - BACKGROUND: Fruit and vegetable consumption is low in the Netherlands and a key
      target in healthy diet promotion. However, hardly any information is available on
      differences in fruit and vegetable consumption between Dutch children and ethnic
      minority children. Therefore, the aim of present study was to determine
      differences in usual fruit and vegetable intake between native Dutch and non
      Western ethnic minority children and to study differences in and mediating
      effects of potential psychosocial and environmental determinants. METHODS:
      Ethnicity, usual fruit and vegetable consumption, psychosocial and environmental
      determinants and mothers' educational level were measured with a self
      administered questionnaire during school hours in primary schools in Rotterdam,
      the Netherlands. Complete data was available for 521 10-11 year-old-children, of
      which 50.5% of non-Western origin. Differences between the groups regarding
      potential determinants and fruit and vegetable intake were assessed with Mann
      Whitney tests or multiple regression analyses. Multiple regression analyses were
      also conducted to assess mediating effects. RESULTS: Ethnic minority girls ate
      fruit more frequently (1.41 +/- 1.0 times/day) than Dutch girls (1.03 +/- 0.82
      times/day); no differences in frequency of intake were found for vegetables or
      among boys. Ethnic differences were found for almost all potential determinants.
      The Dutch children reported lower scores on these determinants than the ethnic
      minority children, except for perceived self-efficacy and barriers to eat fruit
      and vegetables. Knowledge of recommendations and facilitating behaviors of the
      parents mediated the association between ethnicity and fruit consumption among
      girls. CONCLUSION: Ethnic minority girls in the Netherlands appear to have more
      favorable fruit intakes than Dutch girls, and ethnic minority children in general
      show more positive prerequisites for fruit and vegetable consumption.
      Interventions addressing multi-ethnic populations of children must take such
      differences into account.

PMID- 16995937
TI  - Extending basic principles of measurement models to the design and validation of
      Patient Reported Outcomes.
AB  - A recently published article by the Scientific Advisory Committee of the Medical
      Outcomes Trust presents guidelines for selecting and evaluating health status and
      health-related quality of life measures used in health outcomes research. In
      their article, they propose a number of validation and performance criteria with
      which to evaluate such self-report measures. We provide an alternate, yet
      complementary, perspective by extending the types of measurement models which are
      available to the instrument designer. During psychometric development or
      selection of a Patient Reported Outcome measure it is necessary to determine
      which, of the five types of measurement models, the measure is based on; 1) a
      Multiple Effect Indicator model, 2) a Multiple Cause Indicator model, 3) a Single
      Item Effect Indicator model, 4) a Single Item Cause Indicator model, or 5) a
      Mixed Multiple Indicator model. Specification of the measurement model has a
      major influence on decisions about item and scale design, the appropriate
      application of statistical validation methods, and the suitability of the
      resulting measure for a particular use in clinical and population-based outcomes
      research activities.

PMID- 16995938
TI  - Origin of mitochondrial DNA diversity of domestic yaks.
AB  - BACKGROUND: The domestication of plants and animals was extremely important
      anthropologically. Previous studies have revealed a general tendency for
      populations of livestock species to include deeply divergent maternal lineages,
      indicating that they were domesticated in multiple, independent events from
      genetically discrete wild populations. However, in water buffalo, there are
      suggestions that a similar deep maternal bifurcation may have originated from a
      single population. These hypotheses have rarely been rigorously tested because of
      a lack of sufficient wild samples. To investigate the origin of the domestic yak
      (Poephagus grunnies), we analyzed 637 bp of maternal inherited mtDNA from 13 wild
      yaks (including eight wild yaks from a small population in west Qinghai) and 250
      domesticated yaks from major herding regions. RESULTS: The domestic yak
      populations had two deeply divergent phylogenetic groups with a divergence time
      of > 100,000 yrs BP. We here show that haplotypes clustering with two deeply
      divergent maternal lineages in domesticated yaks occur in a single, small, wild
      population. This finding suggests that all domestic yaks are derived from a
      single wild gene pool. However, there is no clear correlation of the mtDNA
      phylogenetic clades and the 10 morphological types of sampled yaks indicating
      that the latter diversified recently. Relatively high diversity was found in
      Qinghai and Tibet around the current wild distribution, in accordance with
      previous suggestions that the earliest domestications occurred in this region.
      Conventional molecular clock estimation led to an unrealistic early dating of the
      start of the domestication. However, Bayesian estimation of the coalescence time
      allowing a relaxation of the mutation rate are better in agreement with a
      domestication during the Holocene as supported by archeological records.
      CONCLUSION: The information gathered here and the previous studies of other
      animals show that the demographic histories of domestication of livestock species
      were highly diverse despite the common general feature of deeply divergent
      maternal lineages. The results further suggest that domestication of local wild
      prey ungulate animals was a common occurrence during the development of human
      civilization following the postglacial colonization in different locations of the
      world, including the high, arid Qinghai-Tibetan Plateau.

PMID- 16995939
TI  - A microsatellite-based consensus linkage map for species of Eucalyptus and a
      novel set of 230 microsatellite markers for the genus.
AB  - BACKGROUND: Eucalypts are the most widely planted hardwood trees in the world
      occupying globally more than 18 million hectares as an important source of carbon
      neutral renewable energy and raw material for pulp, paper and solid wood.
      Quantitative Trait Loci (QTLs) in Eucalyptus have been localized on pedigree
      specific RAPD or AFLP maps seriously limiting the value of such QTL mapping
      efforts for molecular breeding. The availability of a genus-wide genetic map with
      transferable microsatellite markers has become a must for the effective
      advancement of genomic undertakings. This report describes the development of a
      novel set of 230 EMBRA microsatellites, the construction of the first
      comprehensive microsatellite-based consensus linkage map for Eucalyptus and the
      consolidation of existing linkage information for other microsatellites and
      candidate genes mapped in other species of the genus. RESULTS: The consensus map
      covers approximately 90% of the recombining genome of Eucalyptus, involves 234
      mapped EMBRA loci on 11 linkage groups, an observed length of 1,568 cM and a mean
      distance between markers of 8.4 cM. A compilation of all microsatellite linkage
      information published in Eucalyptus allowed us to establish the homology among
      linkage groups between this consensus map and other maps published for E.
      globulus. Comparative mapping analyses also resulted in the linkage group
      assignment of other 41 microsatellites derived from other Eucalyptus species as
      well as candidate genes and QTLs for wood and flowering traits published in the
      literature. This report significantly increases the availability of
      microsatellite markers and mapping information for species of Eucalyptus and
      corroborates the high conservation of microsatellite flanking sequences and locus
      ordering between species of the genus. CONCLUSION: This work represents an
      important step forward for Eucalyptus comparative genomics, opening stimulating
      perspectives for evolutionary studies and molecular breeding applications. The
      generalized use of an increasingly larger set of interspecific transferable
      markers and consensus mapping information, will allow faster and more detailed
      investigations of QTL synteny among species, validation of expression-QTL across
      variable genetic backgrounds and positioning of a growing number of candidate
      genes co-localized with QTLs, to be tested in association mapping experiments.

PMID- 16995940
TI  - In silico and in vivo splicing analysis of MLH1 and MSH2 missense mutations shows
      exon- and tissue-specific effects.
AB  - BACKGROUND: Abnormalities of pre-mRNA splicing are increasingly recognized as an
      important mechanism through which gene mutations cause disease. However, apart
      from the mutations in the donor and acceptor sites, the effects on splicing of
      other sequence variations are difficult to predict. Loosely defined exonic and
      intronic sequences have been shown to affect splicing efficiency by means of
      silencing and enhancement mechanisms. Thus, nucleotide substitutions in these
      sequences can induce aberrant splicing. Web-based resources have recently been
      developed to facilitate the identification of nucleotide changes that could alter
      splicing. However, computer predictions do not always correlate with in vivo
      splicing defects. The issue of unclassified variants in cancer predisposing genes
      is very important both for the correct ascertainment of cancer risk and for the
      understanding of the basic mechanisms of cancer gene function and regulation.
      Therefore we aimed to verify how predictions that can be drawn from in silico
      analysis correlate with results obtained in an in vivo splicing assay. RESULTS:
      We analysed 99 hMLH1 and hMSH2 missense mutations with six different algorithms.
      Transfection of three different cell lines with 20 missense mutations, showed
      that a minority of them lead to defective splicing. Moreover, we observed that
      some exons and some mutations show cell-specific differences in the frequency of
      exon inclusion. CONCLUSION: Our results suggest that the available algorithms,
      while potentially helpful in identifying splicing modulators especially when they
      are located in weakly defined exons, do not always correspond to an obvious
      modification of the splicing pattern. Thus caution must be used in assessing the
      pathogenicity of a missense or silent mutation with prediction programs. The
      variations observed in the splicing proficiency in three different cell lines
      suggest that nucleotide changes may dictate alternative splice site selection in
      a tissue-specific manner contributing to the widely observed phenotypic
      variability in inherited cancers.

PMID- 16995941
TI  - CROPPER: a metagene creator resource for cross-platform and cross-species
      compendium studies.
AB  - BACKGROUND: Current genomic research methods provide researchers with enormous
      amounts of data. Combining data from different high-throughput research
      technologies commonly available in biological databases can lead to novel
      findings and increase research efficiency. However, combining data from different
      heterogeneous sources is often a very arduous task. These sources can be
      different microarray technology platforms, genomic databases, or experiments
      performed on various species. Our aim was to develop a software program that
      could facilitate the combining of data from heterogeneous sources, and thus allow
      researchers to perform genomic cross-platform/cross-species studies and to use
      existing experimental data for compendium studies. RESULTS: We have developed a
      web-based software resource, called CROPPER that uses the latest genomic
      information concerning different data identifiers and orthologous genes from the
      Ensembl database. CROPPER can be used to combine genomic data from different
      heterogeneous sources, allowing researchers to perform cross-platform/cross
      species compendium studies without the need for complex computational tools or
      the requirement of setting up one's own in-house database. We also present an
      example of a simple cross-platform/cross-species compendium study based on
      publicly available Parkinson's disease data derived from different sources.
      CONCLUSION: CROPPER is a user-friendly and freely available web-based software
      resource that can be successfully used for cross-species/cross-platform
      compendium studies.

PMID- 16995942
TI  - Flip-Flop HSV-BAC: bacterial artificial chromosome based system for rapid
      generation of recombinant herpes simplex virus vectors using two independent site
      specific recombinases.
AB  - BACKGROUND: Oncolytic herpes simplex virus (HSV) vectors that specifically
      replicate in and kill tumor cells sparing normal cells are a promising cancer
      therapy. Traditionally, recombinant HSV vectors have been generated through
      homologous recombination between the HSV genome and a recombination plasmid,
      which usually requires laborious screening or selection and can take several
      months. Recent advances in bacterial artificial chromosome (BAC) technology have
      enabled cloning of the whole HSV genome as a BAC plasmid and subsequent
      manipulation in E. coli. Thus, we sought a method to generate recombinant
      oncolytic HSV vectors more easily and quickly using BAC technology. RESULTS: We
      have developed an HSV-BAC system, termed the Flip-Flop HSV-BAC system, for the
      rapid generation of oncolytic HSV vectors. This system has the following
      features: (i) two site-specific recombinases, Cre and FLPe, are used sequentially
      to integrate desired sequences and to excise the BAC sequences, respectively; and
      (ii) the size of the HSV-BAC-insert genome exceeds the packaging limit of HSV so
      only correctly recombined virus grows efficiently. We applied this to the
      construction of an HSV-BAC plasmid that can be used for the generation of
      transcriptionally-targeted HSV vectors. BAC sequences were recombined into the
      UL39 gene of HSV ICP4-deletion mutant d120 to generate M24-BAC virus, from which
      HSV-BAC plasmid pM24-BAC was isolated. An ICP4 expression cassette driven by an
      exogenous promoter was re-introduced to pM24-BAC by Cre-mediated recombination
      and nearly pure preparations of recombinant virus were obtained typically in two
      weeks. Insertion of the ICP4 coding sequence alone did not restore viral
      replication and was only minimally better than an ICP4-null construct, whereas
      insertion of a CMVIE promoter-ICP4 transgene (bM24-CMV) efficiently drove viral
      replication. The levels of bM24-CMV replication in tumor cells varied
      considerably compared to hrR3 (UL39 mutant). CONCLUSION: Our Flip-Flop HSV-BAC
      system enables rapid generation of HSV vectors carrying transgene inserts. By
      introducing a tumor-specific-promoter-driven ICP4 cassette into pM24-BAC using
      this system, one should be able to generate transcriptionally-targeted oncolytic
      HSV vectors. We believe this system will greatly facilitate the screening of a
      plethora of clinically useful tumor-specific promoters in the context of
      oncolytic HSV vectors.

PMID- 16995944
TI  - Observation of the low frequency vibrational modes of bacteriophage M13 in water
      by Raman spectroscopy.
AB  - BACKGROUND: Recently, a technique which departs radically from conventional
      approaches has been proposed. This novel technique utilizes biological objects
      such as viruses as nano-templates for the fabrication of nanostructure elements.
      For example, rod-shaped viruses such as the M13 phage and tobacco mosaic virus
      have been successfully used as biological templates for the synthesis of
      semiconductor and metallic nanowires. RESULTS AND DISCUSSION: Low wave number
      (<or= 20 cm-1) acoustic vibrations of the M13 phage have been studied using Raman
      spectroscopy. The experimental results are compared with theoretical calculations
      based on an elastic continuum model and appropriate Raman selection rules derived
      from a bond polarizability model. The observed Raman mode has been shown to
      belong to one of the Raman-active axial torsion modes of the M13 phage protein
      coat. CONCLUSION: It is expected that the detection and characterization of this
      low frequency vibrational mode can be used for applications in nanotechnology
      such as for monitoring the process of virus functionalization and self-assembly.
      For example, the differences in Raman spectra can be used to monitor the coating
      of virus with some other materials and nano-assembly process, such as attaching a
      carbon nanotube or quantum dots.

PMID- 16995945
TI  - Molecular and immunological characterization of allergens from the
      entomopathogenic fungus Beauveria bassiana.
AB  - BACKGROUND: Entomopathogenic fungi such as Beauveria bassiana are considered
      promising biological control agents for a variety of arthropod pests. Beauveria
      species, however, have the potential to elicit allergenic reactions in humans,
      although no specific allergens have been characterized to date. METHODS: Four
      putative allergens were identified within B. bassiana expressed sequence tag
      (EST) datasets. IgE-reactivity studies were performed using sera from patients
      displaying mold allergies against recombinant B. bassiana proteins expressed in
      E. coli. RESULTS: Full length cDNA and genomic nucleotide sequences of four
      potential B. bassiana allergens were isolated. BLASTX search results led to their
      putative designation as follows; Bb-Eno1, with similarity to fungal enolases; Bb
      f2, similar to the Aspergillus fumigatus major allergen, Asp f2 and to a
      fibrinogen binding mannoprotein; Bb-Ald, similar to aldehyde dehydrogenases; and
      Bb-Hex, similar to N-acetyl-hexosaminadases. All four genes were cloned into E.
      coli expression systems and recombinant proteins were produced. Immunoblots of E.
      coli extracts probed with pooled as well as individual human sera from patients
      displaying mould allergies demonstrated IgE reactivity versus recombinant Bb-Eno1
      and Bb-Ald. CONCLUSION: Four putative Beauveria bassiana allergens were
      identified. Recombinant proteins corresponding to two of the four, Bb-Eno1 and Bb
      Ald were bound by sera IgEs derived from patients with fungal allergies. These
      data confirm the potential allergenicity of B. bassiana by identification of
      specific human IgE reactive epitopes.

PMID- 16995946
TI  - Support for immunization registries among parents of vaccinated and unvaccinated
      school-aged children: a case control study.
AB  - BACKGROUND: Immunizations have reduced childhood vaccine preventable disease
      incidence by 98-100%. Continued vaccine preventable disease control depends on
      high immunization coverage. Immunization registries help ensure high coverage by
      recording childhood immunizations administered, generating reminders when
      immunizations are due, calculating immunization coverage and identifying pockets
      needing immunization services, and improving vaccine safety by reducing over
      immunization and providing data for post-licensure vaccine safety studies.
      Despite substantial resources directed towards registry development in the U.S.,
      only 48% of children were enrolled in a registry in 2004. Parental attitudes
      likely impact child participation. Consequently, the purpose of this study was to
      assess the attitudes of parents of vaccinated and unvaccinated school-aged
      children regarding: support for immunization registries; laws authorizing
      registries and mandating provider reporting; opt-in versus opt-out registry
      participation; and financial worth and responsibility of registry development and
      implementation. METHODS: A case control study of parents of 815 children exempt
      from school vaccination requirements and 1630 fully vaccinated children was
      conducted. Children were recruited from 112 elementary schools in Colorado,
      Massachusetts, Missouri, and Washington. Surveys administered to the parents,
      asked about views on registries and perceived utility and safety of vaccines.
      Parental views were summarized and logistic regression models compared
      differences between parents of exempt and vaccinated children. RESULTS: Surveys
      were completed by 56.1% of respondents. Fewer than 10% of parents were aware of
      immunization registries in their communities. Among parents aware of registries,
      exempt children were more likely to be enrolled (65.0%) than vaccinated children
      (26.5%) (p value = 0.01). A substantial proportion of parents of exempt children
      support immunization registries, particularly if registries offer choice for
      participation. Few parents of vaccinated (6.8%) and exempt children (6.7%) were
      aware of laws authorizing immunization registries. Support for laws authorizing
      registries and requiring health care providers to report to registries was more
      common among parents of vaccinated than exempt children. Most parents believed
      that the government, vaccine companies or insurance companies should pay for
      registries. CONCLUSION: Parental support for registries was relatively high.
      Parental support for immunization registries may increase with greater parental
      awareness of the risks of vaccine preventable diseases and utility of
      vaccination.

PMID- 16995943
TI  - Identification and comparative analysis of sixteen fungal peptidyl-prolyl
      cis/trans isomerase repertoires.
AB  - BACKGROUND: The peptidyl-prolyl cis/trans isomerase (PPIase) class of proteins is
      present in all known eukaryotes, prokaryotes, and archaea, and it is comprised of
      three member families that share the ability to catalyze the cis/trans
      isomerisation of a prolyl bond. Some fungi have been used as model systems to
      investigate the role of PPIases within the cell, however how representative these
      repertoires are of other fungi or humans has not been fully investigated.
      RESULTS: PPIase numbers within these fungal repertoires appears associated with
      genome size and orthology between repertoires was found to be low. Phylogenetic
      analysis showed the single-domain FKBPs to evolve prior to the multi-domain
      FKBPs, whereas the multi-domain cyclophilins appear to evolve throughout
      cyclophilin evolution. A comparison of their known functions has identified,
      besides a common role within protein folding, multiple roles for the cyclophilins
      within pre-mRNA splicing and cellular signalling, and within transcription and
      cell cycle regulation for the parvulins. However, no such commonality was found
      with the FKBPs. Twelve of the 17 human cyclophilins and both human parvulins, but
      only one of the 13 human FKBPs, identified orthologues within these fungi. hPar14
      orthologues were restricted to the Pezizomycotina fungi, and R. oryzae is unique
      in the known fungi in possessing an hCyp33 orthologue and a TPR-containing FKBP.
      The repertoires of Cryptococcus neoformans, Aspergillus fumigatus, and
      Aspergillus nidulans were found to exhibit the highest orthology to the human
      repertoire, and Saccharomyces cerevisiae one of the lowest. CONCLUSION: Given
      this data, we would hypothesize that: (i) the evolution of the fungal PPIases is
      driven, at least in part, by the size of the proteome, (ii) evolutionary
      pressures differ both between the different PPIase families and the different
      fungi, and (iii) whilst the cyclophilins and parvulins have evolved to perform
      conserved functions, the FKBPs have evolved to perform more variable roles. Also,
      the repertoire of Cryptococcus neoformans may represent a better model fungal
      system within which to study the functions of the PPIases as its genome size and
      genetic tractability are equal to those of Saccharomyces cerevisiae, whilst its
      repertoires exhibits greater orthology to that of humans. However, further
      experimental investigations are required to confirm this.

PMID- 16995948
TI  - Evaluating Michigan's community hospital access: spatial methods for decision
      support.
AB  - BACKGROUND: Community hospital placement is dictated by a diverse set of
      geographical factors and historical contingency. In the summer of 2004, a multi
      organizational committee headed by the State of Michigan's Department of
      Community Health approached the authors of this paper with questions about how
      spatial analyses might be employed to develop a revised community hospital
      approval procedure. Three objectives were set. First, the committee needed
      visualizations of both the spatial pattern of Michigan's population and its 139
      community hospitals. Second, the committee required a clear, defensible
      assessment methodology to quantify access to existing hospitals statewide, taking
      into account factors such as distance to nearest hospital and road network
      density to estimate travel time. Third, the committee wanted to contrast the
      spatial distribution of existing community hospitals with a theoretical
      configuration that best met statewide demand. This paper presents our efforts to
      first describe the distribution of Michigan's current community hospital pattern
      and its people, and second, develop two models, access-based and demand-based, to
      identify areas with inadequate access to existing hospitals. RESULTS: Using the
      product from the access-based model and contiguity and population criteria, two
      areas were identified as being "under-served." The lower area, located
      north/northeast of Detroit, contained the greater total land area and population
      of the two areas. The upper area was centered north of Grand Rapids. A demand
      based model was applied to evaluate the existing facility arrangement by
      allocating daily bed demand in each ZIP code to the closest facility. We found
      1,887 beds per day were demanded by ZIP centroids more than 16.1 kilometers from
      the nearest existing hospital. This represented 12.7% of the average statewide
      daily bed demand. If a 32.3 kilometer radius was employed, unmet demand dropped
      to 160 beds per day (1.1%). CONCLUSION: Both modeling approaches enable
      policymakers to identify under-served areas. Ultimately this paper is concerned
      with the intersection of spatial analysis and policymaking. Using the best
      scientific practice to identify locations of under-served populations based on
      many factors provides policymakers with a powerful tool for making good
      decisions.

PMID- 16995947
TI  - Outcome of urogenital infection with Chlamydia muridarum in CD14 gene knockout
      mice.
AB  - BACKGROUND: CD14 has been postulated to play a role in chlamydial immunity and
      immunopathology. There is evidence to support this role in human infections but
      its function in a mouse model has not been investigated. METHODS: Female CD14
      gene knockout and C57BL/6J wild type mice were infected intravaginally with
      Chlamydia muridarum. The infection course was monitored by detection of viable
      chlamydiae from serially collected cervical-vaginal swabs. The sequela of tubal
      factor infertility was assessed using hydrosalpinx formation as a surrogate
      marker. RESULTS: A significantly abbreviated infection course was observed in the
      CD14 gene knockout mice but hydrosalpinx formation occurred at similar rates
      between the two groups. CONCLUSION: Involvement of CD14 during chlamydial
      infection impedes infection resolution but this does not affect the sequela of
      infertility as assessed by hydrosalpinx formation.

PMID- 16995949
TI  - In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model.
AB  - BACKGROUND: ATP is an important signalling molecule in the peripheral and central
      nervous system. Both glioma growth and tumor resection induces cell death, thus
      liberating nucleotides to the extracellular medium. Nucleotides are hydrolyzed
      very slowly by gliomas when compared with astrocytes and induce neuronal cell
      death and glioma proliferation. The objective of the present study was to test
      the involvement of extracellular ATP in glioblastoma growth in a rat glioma
      model. METHODS: To deplete the extracellular ATP, the enzyme apyrase was tested
      on the treatment of gliomas implanted in the rats CNS. One million glioma C6
      cells in 3 microliters of DMEM/FCS were injected in the right striata of male
      Wistar rats, 250-270 g. After 20 days, the rats were decapitated and the brain
      sectioning and stained with hematoxylin and eosine. We performed
      immunohistochemical experiments with Ki67, CD31 and VEGF. Total RNA was isolated
      from cultured glioma C6 cells and the cDNA was analyzed by Real Time-PCR with
      primers for the NTPDase family. RESULTS: C6 glioma cells effectively have a low
      expression of all NTPDases investigated, in comparison with normal astrocytes.
      The implanted glioma co-injected with apyrase had a significant reduction in the
      tumor size (p < 0.05) when compared with the rats injected only with gliomas or
      with gliomas plus inactivated apyrase. According to the pathological analysis,
      the malignant gliomas induced by C6 injection and co-injected with apyrase
      presented a significant reduction in the mitotic index and other histological
      characteristics that indicate a less invasive/proliferative tumor. Reduction of
      proliferation induced by apyrase co-injection was confirmed by counting the
      percentage of Ki67 positive glioma cell nuclei. According to counts with CD31,
      vessel density and neoformation was higher in the C6 group 20 days after
      implantation. Confirming this observation, rats treated with apyrase presented
      less VEGF staining in comparison to the control group. CONCLUSION: These results
      indicate that the participation of extracellular ATP and the ecto-nucleotidases
      may be associated with the development of this type of brain tumor in an in vivo
      glioma model.

PMID- 16995951
TI  - A rare case of renal oncocytoma associated with erythrocytosis: case report.
AB  - BACKGROUND: Oncocytomas are benign tumors of the kidney that are usually
      diagnosed postoperatively due to differential diagnostic problems from renal cell
      carcinoma. Although the latter are neoplasms that have been associated with
      erythrocytosis in 3.5% of cases, there are no reports in the literature about a
      similar occurrence in oncocytomas. CASE PRESENTATION: In this case report we
      present a unique case of a right lower pole oncocytoma associated with
      erythrocytosis. Erythrocytosis subsided after partial nephrectomy. CONCLUSION:
      Erythrocytosis can sometimes occur in association with renal oncocytomas.

PMID- 16995950
TI  - Moderate exercise and chronic stress produce counteractive effects on different
      areas of the brain by acting through various neurotransmitter receptor subtypes:
      a hypothesis.
AB  - BACKGROUND: Regular, "moderate", physical exercise is an established non
      pharmacological form of treatment for depressive disorders. Brain lateralization
      has a significant role in the progress of depression. External stimuli such as
      various stressors or exercise influence the higher functions of the brain
      (cognition and affect). These effects often do not follow a linear course.
      Therefore, nonlinear dynamics seem best suited for modeling many of the
      phenomena, and putative global pathways in the brain, attributable to such
      external influences. HYPOTHESIS: The general hypothesis presented here considers
      only the nonlinear aspects of the effects produced by "moderate" exercise and
      "chronic" stressors, but does not preclude the possibility of linear responses.
      In reality, both linear and nonlinear mechanisms may be involved in the final
      outcomes. The well-known neurotransmitters serotonin (5-HT), dopamine (D) and
      norepinephrine (NE) all have various receptor subtypes. The article hypothesizes
      that 'Stress' increases the activity/concentration of some particular subtypes of
      receptors (designated nts) for each of the known (and unknown) neurotransmitters
      in the right anterior (RA) and left posterior (LP) regions (cortical and
      subcortical) of the brain, and has the converse effects on a different set of
      receptor subtypes (designated nth). In contrast, 'Exercise' increases nth
      activity/concentration and/or reduces nts activity/concentration in the LA and RP
      areas of the brain. These effects may be initiated by the activation of Brain
      Derived Neurotrophic Factor (BDNF) (among others) in exercise and its suppression
      in stress. CONCLUSION: On the basis of this hypothesis, a better understanding of
      brain neurodynamics might be achieved by considering the oscillations caused by
      single neurotransmitters acting on their different receptor subtypes, and the
      temporal pattern of recruitment of these subtypes. Further, appropriately
      designed and planned experiments will not only corroborate such theoretical
      models, but also shed more light on the underlying brain dynamics.

PMID- 16995952
TI  - Analytical model of peptide mass cluster centres with applications.
AB  - BACKGROUND: The elemental composition of peptides results in formation of
      distinct, equidistantly spaced clusters across the mass range. The property of
      peptide mass clustering is used to calibrate peptide mass lists, to identify and
      remove non-peptide peaks and for data reduction. RESULTS: We developed an
      analytical model of the peptide mass cluster centres. Inputs to the model
      included, the amino acid frequencies in the sequence database, the average length
      of the proteins in the database, the cleavage specificity of the proteolytic
      enzyme used and the cleavage probability. We examined the accuracy of our model
      by comparing it with the model based on an in silico sequence database digest. To
      identify the crucial parameters we analysed how the cluster centre location
      depends on the inputs. The distance to the nearest cluster was used to calibrate
      mass spectrometric peptide peak-lists and to identify non-peptide peaks.
      CONCLUSION: The model introduced here enables us to predict the location of the
      peptide mass cluster centres. It explains how the location of the cluster centres
      depends on the input parameters. Fast and efficient calibration and filtering of
      non-peptide peaks is achieved by a distance measure suggested by Wool and
      Smilansky.

PMID- 16995953
TI  - Knowledge, attitude and practice of breastfeeding in the north of Jordan: a cross
      sectional study.
AB  - BACKGROUND: In Jordan, as in neighboring countries in the Middle East, higher
      education and higher employment rates in recent years among women have had an
      impact on traditionally based infant feeding. The objective of this study was to
      evaluate practice, knowledge and attitude to breastfeeding and to assess factors
      associated with breastfeeding among women in the north of Jordan. METHODS: A
      cross sectional study was carried out between 15 July 2003 and 15 August 2003. A
      total of 344 women with children aged between 6 months and 3 years from five
      different villages in the north of Jordan were randomly selected and interviewed.
      Information regarding participants' demographics, infant feeding in first six
      months of life, knowledge and attitude towards breastfeeding was collected.
      RESULTS: Full breastfeeding was reported by 58.3%, mixed feeding was reported by
      30.3% and infant formula feeding was reported by 11.4%. Almost one third of the
      full breastfeeding group did so for 6-12 months, and almost two thirds did
      continue breastfeeding for more than one year. Employed women were more likely
      not to practice full breastfeeding compared to unemployed women (odds ratio 3.34,
      95% CI 1.60, .98), and women who had cesarian delivery were more likely not to
      practice full breastfeeding compared to those who had vaginal delivery (odds
      ratio 2.36, 95% CI 1.17, 4.78). Jordanian women had a positive attitude but work
      place and short maternity leaves had a negative impact on breastfeeding.
      CONCLUSION: This study showed that a high proportion of Jordanian women did
      breastfeed for more than one year. However, working women and those who deliver
      by caesarean section were less likely to breastfeed. It is speculated that
      adopting facilitatory measures at hospitals and work place could increase the
      rate of full breastfeeding.

PMID- 16995954
TI  - Quantification of Epstein-Barr virus DNA load, interleukin-6, interleukin-10,
      transforming growth factor-beta1 and stem cell factor in plasma of patients with
      nasopharyngeal carcinoma.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among
      the Chinese populations in Southern China and South East Asia. Epstein-Barr virus
      (EBV) is known to be an important etiologic agent of NPC and the viral gene
      products are frequently detected in NPC tissues along with elevated antibody
      titres to the viral proteins (VCA and EA) in a majority of patients. Elevated
      plasma EBV DNA load is regarded as an important marker for the presence of the
      disease and for the monitoring of disease progression. However, other
      serum/plasma parameters such as the levels of certain interleukins and growth
      factors have also been implicated in NPC. The objectives of the present study
      are, 1) to investigate the correlations between plasma EBV DNA load and the
      levels of interleukin (IL)-6, IL-10, TGF-beta1 and SCF (steel factor) and 2) to
      relate these parameters to the stages of NPC and the effect of treatment.
      METHODS: A total of 78 untreated NPC patients were enrolled in this study. Of
      these, 51 were followed-up after treatment. The remaining patients had irregular
      or were lost to follow-up. Plasma EBV DNA was quantified using real-time
      quantitative PCR. The levels of plasma interleukins and growth factors were
      quantified using ELISA. RESULTS: A significant decrease in EBV DNA load was
      detected in plasma of untreated NPC patients (1669 +/- 637 copies/mL; n = 51)
      following treatment (57 +/- 37 copies/mL, p < 0.05); n = 51). Plasma EBV DNA load
      was shown to be a good prognosticator for disease progression and clinical
      outcome in five of the follow-up patients. A significant difference in IL-6
      levels was noted between the untreated patients (164 +/- 37 pg/mL; n = 51) and
      following treatment (58 +/- 16 pg/mL, p < 0.05; n = 51). Positive correlations
      between EBV DNA load and IL-10 (r(49) = 0.535, p < 0.01), between IL6 and IL-10
      (r(49) = 0.474, p < 0.01) and between TGF and SCF (r(49) = 0.464, p < 0.01) were
      observed in patients following treatment. None of the parameters tested including
      IgA-VCA were associated with tumour stages. CONCLUSION: We conclude that among
      the parameters investigated, EBV DNA load and IL-6 levels were promising markers
      for the presence of NPC and for the assessment of treatment outcome.

PMID- 16995955
TI  - Psychometric properties of the Centers for Disease Control and Prevention Health
      Related Quality of Life (CDC HRQOL) items in adults with arthritis.
AB  - BACKGROUND: Measuring health-related quality of life (HRQOL) is important in
      arthritis and the SF-36v2 is the current state-of-the-art. It is only emerging
      how well the Centers for Disease Control and Prevention (CDC) HRQOL measures
      HRQOL for people with arthritis. This study's purpose is to assess the
      psychometric properties of the 9-item CDC HRQOL (4-item Healthy Days Core Module
      and 5-item Healthy Days Symptoms Module) in an arthritis sample using the SF-36v2
      as a comparison. METHODS: In Fall 2002, a cross-sectional study acquired survey
      data including the CDC HRQOL and SF-36v2 from 2 North Carolina populations of
      adult patients reporting osteoarthritis, rheumatoid arthritis, and fibromyalgia;
      2182 (52%) responded. The first item of both the CDC HRQOL and the SF-36v2 was
      general health (GEN). All 8 other CDC HRQOL items ask for the number of days in
      the past 30 days that respondents experienced various aspects of HRQOL.
      Exploratory principal components analyses (PCA) were conducted on each sample and
      the combined samples of the CDC HRQOL. The multitrait-multimethod matrix (MTMM)
      was used to compute correlations between each trait (physical health and mental
      health) and between each method of measurement (CDC HRQOL and SF36v2). The
      relative contribution of the CDC HRQOL in predicting the physical component
      summary (PCS) and the mental component summary (MCS) was determined by regressing
      the CDC HRQOL items on the PCS and MCS scales. RESULTS: All 9 CDC HRQOL items
      loaded primarily onto 1 factor (explaining 57% of the item variance) representing
      a reasonable solution for capturing overall HRQOL. After rotation a 2 factor
      interpretation for the 9 items was clear, with 4 items capturing physical health
      (physical, activity, pain, and energy days) and 3 items capturing mental health
      (mental, depression, and anxiety days). All of the loadings for these two factors
      were greater than 0.70. The CDC HRQOL physical health factor correlated with PCS
      (r = -.78, p < 0.0001) and the mental health factor correlated with MCS (r = 
      .71, p < 0.0001). The relative contribution of the CDC HRQOL in predicting PCS
      was 73% (R2 = .73) when GEN was included in the CDC HRQOL score and 65% (R2 =
      .65) when GEN was removed. The relative contribution of the CDC HRQOL in
      predicting MCS was 56% (R2 = .56) when GEN was included and removed. CONCLUSION:
      The CDC HRQOL appears to have strong psychometric properties in individuals with
      arthritis in both community-based and subspecialty clinical settings. The 9 item
      CDC HRQOL is a reasonable measure for overall HRQOL and the two subscales,
      representing physical and mental health, are reasonable when the goal is to
      examine those aspects.

PMID- 16995957
TI  - On the origin and evolution of major morphological characters.
AB  - Although the mathematical principles underpinning population-level evolution are
      now well studied, the origin and evolution of morphological novelties has
      received far less attention. Here, a broad but general theory for how this sort
      of change takes place is outlined, relying on functional continuity, least
      constrained components of morphology, redundancy and preadaptation. At least four
      distinct sorts of redundancy are identified: (i) redundancy arising through
      duplication (amplification); (ii) redundancy arising through regionalisation
      (parcellation); (iii) redundancy arising through functional convergence; and (iv)
      redundancy arising from shared function (functional degeneracy). Although
      organisms are here recognised to be functionally constrained ("burdened", in
      Riedl's terminology), these constraints can be overcome through the combination
      of the four principles given above. Contrary to its common treatment, functional
      constraint is neither an ever-increasing restriction on the scope of evolution,
      nor does it require drastic events to overcome or "break" it. Rather, it is an
      evolutionary quantity, subject to selection at some level. The rules that govern
      morphological evolution are the primary controls on what is allowed to happen in
      the evolution of the overall genotype-phenotype system, suggesting strong
      controls on the sorts of developmental changes that might be associated with
      macroevolution. This model, then, sees organism functionality as the primary
      control on evolvability, with exact genetic make-up being of secondary
      importance. It should prove possible to recast traditional notions of body-plan
      evolution into the formulations of complex system analysis, which in the future
      may prove a unifying discipline for fields as disparate as palaeontology and gene
      regulatory networks. In particular, understanding how morphology can evolve may
      provide the critical link between the ecological and morphological networks that
      are currently the intense focus of evolutionary investigations.

PMID- 16995956
TI  - LIGSITEcsc: predicting ligand binding sites using the Connolly surface and degree
      of conservation.
AB  - BACKGROUND: Identifying pockets on protein surfaces is of great importance for
      many structure-based drug design applications and protein-ligand docking
      algorithms. Over the last ten years, many geometric methods for the prediction of
      ligand-binding sites have been developed. RESULTS: We present LIGSITEcsc, an
      extension and implementation of the LIGSITE algorithm. LIGSITEcsc is based on the
      notion of surface-solvent-surface events and the degree of conservation of the
      involved surface residues. We compare our algorithm to four other approaches,
      LIGSITE, CAST, PASS, and SURFNET, and evaluate all on a dataset of 48
      unbound/bound structures and 210 bound-structures. LIGSITEcsc performs slightly
      better than the other tools and achieves a success rate of 71% and 75%,
      respectively. CONCLUSION: The use of the Connolly surface leads to slight
      improvements, the prediction re-ranking by conservation to significant
      improvements of the binding site predictions. A web server for LIGSITEcsc and its
      source code is available at scoppi.biotec.tu-dresden.de/pocket

PMID- 16995958
TI  - Multiple laryngeal foreign bodies composed of dried fish vertebral bones: a case
      report.
AB  - We present a rare case of tracheostomy for removal of laryngeal foreign bodies
      consisting of three connected fish vertebral bones in a 15-month-old girl. Recent
      endoscopic techniques have made it possible to extract nearly all
      tracheobronchial foreign bodies with rigid bronchoscopes. However, the three
      connected foreign bodies in this report could not be extracted entirely by single
      endoscopy because the glottis as an exit was narrow due to severe oedema.
      Accordingly, tracheostomy was required to assist ventilation, prevent prolonged
      post-operative endotracheal intubation, remove the secondary tracheal foreign
      bodies and to provide a conduit for the introduction of a bronchoscope. This
      suggests that tracheostomy should be considered to avoid the potential dangers of
      severe laryngeal oedema and to secure the route for removal of foreign bodies
      from the trachea when treating patients with multiple laryngeal foreign bodies
      and laryngeal oedema.

PMID- 16995959
TI  - Resistance of Pseudomonas to ciprofloxacin: implications for the treatment of
      malignant otitis externa.
AB  - For fifteen years oral ciprofloxacin has been the standard treatment for
      malignant otitis externa, a sometimes fatal osteomyelitis of the skull base
      usually caused by Pseudomonas aeruginosa. Resistance to ciprofloxacin is
      developing. Over a 16-month period, we saw five cases where malignant otitis
      externa progressed, with the development of cranial nerve palsies in four cases,
      despite oral ciprofloxacin. Prolonged intravenous antibiotic therapy became
      necessary. One case was managed largely as an out-patient, but four patients
      spent many weeks in hospital. Only two cases had diabetes and this was monitored
      and controlled. Pseudomonas aeruginosa was isolated in four of the five cases,
      but antibiotic sensitivity to ciprofloxacin was not determined. In one case a
      later isolate was tested and found to be ciprofloxacin resistant. Progress was
      monitored by serial C-reactive protein (CRP) and white cell count. For diagnosis
      and assessing response to treatment we considered serial magnetic resonance
      imaging or computed tomography more useful than isotope bone scan. There must be
      a readiness to use intravenous antibiotics, as a response to ciprofloxacin can no
      longer be assumed. Bacterial isolates must be tested for sensitivity to
      antibiotics including ciprofloxacin, and further biopsy and culture are essential
      if treatment fails.

PMID- 16995960
TI  - Predictive role of Carhart's notch in pre-operative assessment for middle-ear
      surgery.
AB  - OBJECTIVES: To evaluate the predictive role of the audiometric Carhart's notch
      for the assessment of middle-ear pathology prior to surgical intervention.
      METHOD: In this retrospective analysis, a total of 315 operated ears of 305
      patients were evaluated regarding their pre-operative pure tone audiograms and
      peri-operative findings. The probable relationship between the middle-ear
      pathologies found and the Carhart's notch found on pre-operative pure tone
      audiometry was investigated. Patients with conductive hearing loss who obtained
      at least a 10 dB improvement (at 1 and 2 kHz frequencies) in their bone
      conduction threshold post-operatively were included in the Carhart's notch group.
      The pathologies underlying Carhart's notch were compared. RESULTS: Three hundred
      and fifteen ears of 305 consecutive patients with conductive hearing loss were
      operated on due to middle-ear pathology. In patients with otosclerosis and
      tympanosclerosis, a Carhart's notch was seen at 2 kHz in 28 (93 per cent)
      patients but at 1 kHz in only two (7 per cent). However, in patients with chronic
      otitis media, a Carhart's notch was seen at 1 kHz in 10 (55 per cent) patients
      and at 2 kHz in eight (45 per cent) patients. CONCLUSIONS: Otitis media with
      effusion, tympanosclerosis and congenital malformations should be considered in
      the differential diagnosis of a patient with a Carhart's notch seen on pure tone
      audiometry. A Carhart's notch at 2 kHz indicates stapes footplate fixation,
      whereas one at 1 kHz indicates a mobile stapes footplate; the footplate mobility
      can thus be predicted pre-operatively.

PMID- 16995961
TI  - Analysis of 2167 head and neck cancer patients' management, treatment compliance
      and outcomes from a regional cancer centre, Delhi, India.
AB  - Head and neck cancer care was analysed in 2167 unselected patients for management
      compliance and outcome. Median age was 55 years, with a male to female ratio of
      5.5ratio1. Major sites were oropharynx (32.4 per cent), larynx (19.8 per cent),
      oral (16.6 per cent) and hypopharynx (12.9 per cent). Stage-wise distribution was
      I-II=8.9 per cent, III=20.6 per cent and IV=60.3 per cent and unstaged=10.2 per
      cent. Squamous cell carcinoma was the dominant histology for 90.9 per cent.
      Clinic-based cancer-directed treatment decisions were made for 1905 patients:
      curative intent in 53 per cent, palliative in 35 per cent and for the remaining
      262 (12 per cent) supportive care. Overall, 1209 (56 per cent) patients complied
      with the prescribed treatments; 62 per cent, 54 per cent, and 35 per cent of
      curative, palliative and supportive care intent groups, respectively. Modalities
      were radiotherapy alone (64.6 per cent), combined surgery with irradiation (17.6
      per cent), and chemoradiotherapy (11.2 per cent). Median follow-up periods were
      17.5 and three months in curative and palliative groups respectively. Overall,
      712 (33 per cent) cases received curative therapy, with three-year disease
      specific survival of 49 per cent. Patient compliance was a major obstacle. The
      comparison of this series with the USA, Canada and Norway showed wide disparities
      in stage of presentation and survival.

PMID- 16995962
TI  - Obliteration of the tympanomastoid cavity: long term results of the Rambo
      operation.
AB  - INTRODUCTION: Radical mastoidectomy and tympanomastoid obliteration with fat
      tissue, also called the Rambo operation, is proposed to those patients suffering
      chronic middle-ear disease, with or without cholesteatoma, who have no useful
      hearing in an ear which cannot be kept dry despite all conservative treatment.
      METHODS: We analysed retrospectively a series of 46 patients operated upon in our
      department. Information recorded included the surgical indications, surgical
      observations, post-operative care and complications. All patients were invited to
      comment on their long term anatomical and functional results and to express their
      degree of satisfaction with the procedure. RESULTS: Recurrent infectious episodes
      were observed in seven cases. Residual cholesteatoma were observed in three
      cases. After treatment, these patients did not present with further
      complications. One case presented with multiple episodes of infection with
      recurrences of cholesteatoma and finally had the obliterated cavity transformed
      into an open cavity again. For most of the patients, in the long term (i.e. one
      to 23 years post-operatively (mean eight years)), the operation resulted in a dry
      ear, ending the need for frequent consultations to clean and disinfect diseased
      ears or open cavities. CONCLUSION: Obliteration of the tympanomastoid cavity, as
      proposed by Tom Rambo, shortens considerably the post-operative care period, in
      comparison with canal wall down mastoidectomy, and is therefore indicated if no
      serviceable hearing can be expected. In the long term, the rate of complications
      is low and patients are satisfied.

PMID- 16995963
TI  - Visualization of a high protein concentration in the cochlea of a patient with a
      large endolymphatic duct and sac, using three-dimensional fluid-attenuated
      inversion recovery magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the inner ear of a patient with an enlarged vestibular
      aqueduct and acute hearing deterioration, using three-dimensional fluid
      attenuated inversion recovery (3D FLAIR) magnetic resonance imaging (MRI).
      BACKGROUND: Three-dimensional fluid-attenuated inversion recovery MRI has been
      recently developed to detect haemorrhage and high concentrations of protein.
      Application of this method to inner-ear diseases has not been fully described.
      METHOD: We used 3D FLAIR MRI to evaluate a patient with an enlarged vestibular
      aqueduct and acute hearing deterioration. RESULTS: On 3D FLAIR MRI, this patient
      had high signals in the endolymphatic duct and sac, the vestibule and the cochlea
      and was diagnosed as having a high protein concentration in the inner ear. These
      high signal areas were not detected by T1- and T2-weighted MRI. CONCLUSION: This
      is the first published case in which a high protein concentration in the cochlea
      of a patient with an enlarged vestibular aqueduct was detected by 3D FLAIR MRI.
      These findings strongly supported the theory of the pathophysiology of hearing
      deterioration in patients with an enlarged vestibular aqueduct, which states that
      hyperosmolar fluid in the enlarged endolymphatic sac refluxes into the cochlea,
      resulting in damage to the hair cells. Thus, these finding may help clarify the
      cause of hearing deterioration in the presence of a large endolymphatic duct and
      sac.

PMID- 16995964
TI  - Management of life-threatening airway obstruction caused by benign thyroid
      disease.
AB  - INTRODUCTION: Goitre presenting with acute, life-threatening airway compromise is
      an uncommon indication for thyroid surgery. The management of this critical
      condition is controversial. AIMS: To investigate the incidence of life
      threatening airway compromise in patients with benign goitre, to investigate the
      predisposing factors, and to outline an optimal management policy for such
      critical cases. METHODS: Retrospective review of the medical records of patients
      presenting with life-threatening, acute airway compromise secondary to benign
      thyroid disease, treated by the senior author (CT) between July 1994 and July
      2005. RESULTS: Of a total of 505 thyroid surgery procedures over the 11-year
      period, five patients with benign thyroid disease had presented with life
      threatening, acute airway compromise. Three of the five patients had been
      thyrotoxic and two of these had received an iodine load prior to airway
      compromise. Immediate endotracheal intubation for airway control followed by
      admission to the intensive care unit had been the presentation in two patients.
      An incidental diagnosis of tracheal compression had been made from the computed
      tomography (CT) scan in two patients who had non-resolved obstructive airway
      disease. Emergency thyroidectomy had been performed in all five patients.
      Significant tracheomalacia had been noted in four patients. Following
      thyroidectomy, two patients had required tracheostomy and one had required
      tracheal stenting. CONCLUSION: Chronic obstructive airways disease, substernal
      extension and long-standing goitre are considered as risk factors for developing
      acute, life-threatening airway compromise in the presence of benign thyroid
      disease. A recent iodine load may lead to airway compromise in thyrotoxic
      patients. A CT scan is indicated in cases of unresponsive chronic obstructive
      airways disease to rule out substernal extension of non-palpable goitres. Life
      threatening airway compromise secondary to benign goitres is best treated by
      endotracheal intubation if conservative measures fail, followed by emergency
      thyroidectomy. Following surgery, close observation is mandatory to exclude
      airway compromise due to tracheomalacia and laryngeal oedema.

PMID- 16995965
TI  - The Picture Archiving and Communication System: a useful tool in a case of upper
      oesophageal foreign body.
AB  - We present a case of an oesophageal foreign body (approximately 2x2 cm) which was
      not seen on the initial lateral soft tissue neck X-ray but was detected following
      manipulation of the X-ray using the Picture Archiving and Communication System of
      X-ray viewing. This system gives the user much greater flexibility, including a
      choice of magnification and contrast.

PMID- 16995966
TI  - Intracranial angiosarcoma arising from a schwannoma.
AB  - Angiosarcomas rarely arise from schwannomas, but we describe here a case of
      angiosarcoma that arose from a remnant of a benign vestibular schwannoma that had
      been removed 10 years earlier. The patient was a 66-year-old man with no sign of
      neurofibromatosis. Although we attempted surgical resection, we could not totally
      remove the tumour. The patient died nine months after diagnosis, primarily as
      result of an abscess in the cerebellum and base of the skull. The histological
      diagnosis was confirmed by the immunohistochemical findings of positivity for
      CD34 antigen and S-100 protein in the resected tumour.A review of the literature
      revealed four other cases of angiosarcoma with schwannoma, all of which arose
      from an extracranial nerve. The present case is the first report of an
      angiosarcoma with schwannoma arising from an intracranial locus.

PMID- 16995967
TI  - Tinnitus.
AB  - Chronic idiopathic subjective tinnitus is a common condition affecting around one
      in ten of the population at any given time. For the majority of people it is an
      annoyance rather than a major health issue but for approximately 0.5 per cent of
      the population tinnitus interferes with their ability to pursue a normal life.
      Modern theories of the pathogenesis of the condition concentrate on the central
      auditory system although the peripheral auditory system can be a trigger or
      ignition site for tinnitus. Although a cure remains elusive there are several
      good treatment strategies based on psychological and neurophysiological models of
      tinnitus that promote habituation to the symptom.

PMID- 16995968
TI  - The immunohistochemical expression of p21WAF1/Cip1 and Proliferating cell nuclear
      antigen in laryngeal squamous cell carcinomas.
AB  - The purpose of this study was to assess the significance of the expression of
      p21WAF1/Cip1 and proliferating cell nuclear antigen (PCNA) in human laryngeal
      squamous cell carcinomas. Forty-eight patients (25 supraglottic, 23 glottic) who
      had undergone operations between 1998 and 2003 were included in this study. The
      Envision immunohistochemistry method was utilized to stain these tissue
      specimens. The results showed that the immunostaining of p21WAF1/Cip1 do not show
      any correlation with differentiation, N stage, metastasis, survival, recurrence
      or the laryngeal site of involvement. A significant inverse correlation was
      detected between p21WAF1/Cip1 and the T stage. In contrast, the percentage of
      PCNA labelled cells showed a significant correlation with the T stage, but not
      with other clinicopathological parameters. There were differences in the
      expression of p21WAF1/Cip1 and PCNA between the supraglottic and the glottic
      carcinomas. In conclusion, our findings suggest that p21WAF1/Cip1 and PCNA may
      play an important role in the progression of carcinoma of the supraglottic
      larynx.

PMID- 16995969
TI  - Ice cold carbonated water: a therapy for persistent hyperawareness of pharyngeal
      mucus and throat clearing.
AB  - Chronic throat clearing or a feeling of 'something' at the back of the oropharynx
      or nasopharynx is a common cause for referral to otorhinolaryngology services.
      While treatment of an underlying causative condition might be expected to improve
      these symptoms, in many cases a clear underlying cause is not found. Currently,
      there is no recognized treatment which is effective against these troublesome
      symptoms. This observational study investigated the effectiveness of a regime of
      sipping ice cold carbonated water to try to break the vicious cycle of throat
      clearing. Seventy-two patients with these symptoms who had previously been
      advised to use the regime were contacted with a postal questionnaire. Sixty-three
      per cent of patients documented an improvement in their symptom severity score.
      The most severely and most frequently affected patients had the greatest benefit.
      We conclude that the suggested regime can be effective in breaking the vicious
      cycle of persistent throat-clearing.

PMID- 16995970
TI  - Cystadenocarcinoma (papillary cystadenocarcinoma) of the submandibular gland.
AB  - Cystadenocarcinoma (papillary cystadenocarcinoma) of the salivary gland is a rare
      malignant neoplasm. Major locations of this neoplasm are the parotid gland, the
      sublingual gland, and minor salivary glands, while occurrence in the
      submandibular gland is extremely rare. As far as we know, only one report,
      written in the French language, has been published concerning cystadenocarcinoma
      of the submandibular gland, but no report is available in the English language.
      In this report, we describe a case of cystadenocarcinoma arising from the
      submandibular gland of a 54-year-old male patient. The neoplasm is a low-grade
      carcinoma, and pre-operative examination may not show typical characteristics of
      malignant neoplasms. Therefore, as was true in this case, the differential
      diagnosis from benign lesions is sometimes difficult. This is the first report on
      cystadenocarcinoma of the submandibular gland in the English language and the
      first to show a computed tomography (CT) scan and magnetic resonance imaging
      (MRI) of this neoplasm in the submandibular gland.

PMID- 16995971
TI  - Magnetic resonance imaging scans for vestibulocochlear nerve tumours: what is
      actually found?
AB  - BACKGROUND: Approximately 20 per cent of adult patients presenting to
      otolaryngology clinics have symptoms pertaining to the inner ear. These are
      investigated with magnetic resonance imaging (MRI) internal auditory meatus
      scans. This study analysed all findings from 736 sequential MRI internal auditory
      meatus scans performed on 731 patients over a one year period. METHODS: Six
      hundred and seventy-two patients were included for analysis. Of these, 419 (62.35
      per cent) had normal MRI scans, 221 (32.90 per cent) had MRI findings thought to
      be unrelated to their presenting symptoms, 32 (4.76 per cent) had findings
      thought to be the cause of their symptoms, and eight (1.19 per cent) had the
      typical appearance of an VIIIth nerve schwannoma. CONCLUSIONS: Magnetic resonance
      image scanning of the inner ears and auditory pathways yields a diagnosis of
      VIIIth nerve tumours of the order of 1 per cent, does not show other causes of
      inner-ear symptoms in a further 4 per cent, and shows incidental intra- and
      extracranial abnormalities in a further 33 per cent, most of which are not
      clinically significant.

PMID- 16995972
TI  - Computer-assisted surgery of the paranasal sinuses: technical and clinical
      experience with 368 patients, using the Vector Vision Compact system.
AB  - INTRODUCTION: This paper presents our experience with a navigation system for
      functional endoscopic sinus surgery. In this study, we took particular note of
      the surgical indications and risks and the measurement precision and preparation
      time required, and we present one brief case report as an example. MATERIALS AND
      METHODS: Between 2000 and 2004, we performed functional endoscopic sinus surgery
      on 368 patients at the Ludwig Maximilians University, Munich, Germany. We used
      the Vector Vision Compact system (BrainLAB) with laser registration. The
      indications for surgery ranged from severe nasal polyps and chronic sinusitis to
      malignant tumours of the paranasal sinuses and skull base. RESULTS: The time
      needed for data preparation was less than five minutes. The time required for
      preparation and patient registration depended on the method used and the
      experience of the user. In the later cases, it took 11 minutes on average, using
      Z-Touch registration. The clinical plausibility test produced an average
      deviation of 1.3 mm. The complications of system use comprised one intra
      operative re-registration (18 per cent) and one complete failure (5 per cent).
      Despite the assistance of an accurate working computer, the anterior ethmoidal
      artery was incised in one case. However, in all 368 cases, we experienced no
      cerebrospinal fluid leaks, optic nerve lesions, retrobulbar haematomas or
      intracerebral bleeding. There were no deaths. DISCUSSION: From our experience
      with computer-guided surgical procedures, we conclude that computer-guided
      navigational systems are so accurate that the risk of misleading the surgeon is
      minimal. In the future, their use in certain specialized procedures will be not
      only sensible but mandatory. We recommend their use not only in difficult
      surgical situations but also in routine procedures and for surgical training.

PMID- 16995973
TI  - [Current status and prospectives in research on liver failure].

PMID- 16995974
TI  - [Diagnostic and treatment guidelines for liver failure].

PMID- 16995975
TI  - [Survival analysis on liver failure patients treated with an artificial liver
      support system].
AB  - OBJECTIVE: To evaluate the efficacy of artificial liver support system (ALSS) in
      the treatment of liver failure patients. METHODS: This is a prospective, multi
      center, controlled, large sample clinic trial. 518 patients with liver failure
      from 5 hospitals were studied and followed. All the patients received similar
      pharmacological manipulation according to one and the same protocol but were
      divided into an ALSS treatment group and a control group without ALSS treatment.
      The ALSS treatment procedures included plasma exchange, molecular adsorbent
      recirculating system (MARS), plasma exchange plus hemofiltration and other
      combined nonbioartificial methods. The analysis of survival time was computed
      using the Kaplain-Maier method, and comparison among groups was done using Log
      Rank, Breslow and/or the Tarone-Ware test. RESULTS: Survival time of acute liver
      failure patients was prolonged from 4.0+/-0.2 days to 8.0+/-0.4 days (P=0.004).
      ALSS was shown to be two times more effective. ALSS increased the survival time
      of acute on chronic (A on C) liver failure patients from 27.0+/-1.6 days to
      39.0+/-4.0 days (P less than 0.01). In addition, it increased the survival time
      of the patients in the middle and end stage of subacute liver failure and A on C
      liver failure, but had no significant effects on early stage patients. The
      survival time of middle stage patients was 38.0+/-17.5 days in the control group
      vs 66.0+/-18.6 days in the ALSS group (P less than 0.05). The survival time of
      end stage patients of the control group and the ALSS group was 18.0+/-4.0 days vs
      26.0+/-2.5 days (P less than 0.01). CONCLUSIONS: Multi ALSS treatment is more
      effective than the standard medicinal liver care treatment. Multi-ALSS treatment
      could increase survival time of patients suffering from acute liver failure or A
      on C liver failure, especially in their middle and end stages. It is important
      and necessary to treat these patients with ALSS.

PMID- 16995976
TI  - [Combined non-biological artificial liver in treatment of late stage chronic
      severe hepatitis].
AB  - OBJECTIVE: To explore the clinical effects of combined non-biological artificial
      liver in the treatment of late stage chronic severe hepatitis and especially to
      observe their effects on hepatic encephalopathy, hepatorenal syndrome and
      disturbance of electrolytes. METHODS: 103 chronic severe hepatitis patients were
      treated with the same medical measures, including plasma exchange. Among them, 63
      patients were also treated with combinations of non-biological artificial liver
      (treatment group), and the other 40 patients served as controls (control group).
      The efficacy of the treatments and survival rates of the two groups were
      compared. RESULTS: In the treatment group, the rate of regaining normal
      consciousness was 72.7%, the rate of electrolyte disorder being rectified was
      89.5%, the rate of restoring renal function was 66.7% and the total survival rate
      was 47.6%. In comparison, in the control group the rate of regaining normal
      consciousness was 16.7%, the rate of electrolyte disorder being rectified was
      42.3%, none of their renal functions were restored and the total survival rate
      was 22.5%. The differences between the two groups were significant (chi2=6.56, P
      less than 0.05). CONCLUSION: With other medical treatment, combined non
      biological artificial liver can improve the survival rate of severe hepatitis
      patients.

PMID- 16995977
TI  - [An analysis of the relationship between HBV DNA and HBeAg expression and
      mortality in 799 severe hepatitis patients].
AB  - OBJECTIVE: To evaluate the relationship between mortality and HBVDNA and HBeAg
      expression of severe hepatitis B patients. METHODS: The mortality rates of
      different types of severe hepatitis patients in our hospital during the last five
      years were analysed. HBV DNA was detected using the fluorescence quantitative PCR
      method and the HBeAg expression of severe hepatitis B was studied using a
      microparticle method. RESULTS: (1) Hepatitis B morbidity was 83.5% in each type
      of severe hepatitis, and severe chronic hepatitis B morbidity was 96.77% in each
      type of severe chronic hepatitis. (2) The mortality rate of those with HBV DNA
      more than 1 x 10(5) copies/ml was 53.25% and the mortality of those with HBV DNA
      less than 1 x 10(5) copies/ml was 34.50% (P less than 0.01). The HBeAg expression
      had no influence on the death rate. (3) The death rate descended to 30.38% from
      54.64% (HBV DNA more than 1 x 10(5) copies/ml) when treated with Lamivudine (P
      less than 0.01). CONCLUSION: In severe hepatitis the quantity of virus carried in
      the patient is one of the key factors of mortality; antivirus treatment can lower
      mortality.

PMID- 16995978
TI  - [Detection of HBV specific cytotoxic lymphocytes responses in severe hepatitis B
      patients using MHC-peptide tetramer flow cytometry].
AB  - OBJECTIVE: To explore the role played by HBV antigen specific cytotoxic
      lymphocytes (CTLs) in severe hepatitis B patients. METHODS: Three kinds of HBV
      specific CD8+ T cells responding to HBV core 18-27, polymerase 575-583 and
      envelope 335-343 specific CD8+ T cells were searched with major
      histocompatibility complex (MHC)-peptide tetramer flow cytometry in the patients
      we studied. The cytokines produced by these specific CTLs such as IFNgamma,
      TNFalpha, IL-4, IL-10 were detected using ELISPOT assays. Their ability to lyse
      target cells was analyzed using a CytoTox96 Non-Radioactive Cytotoxicity Assay
      kit (Promega). RESULTS: The number of HBV core 18-27 specific CD8+ T cells was
      significantly higher in the peripheral blood of acute severe hepatitis B group
      patients than that in chronic severe hepatitis group (P less than 0.05), but
      lower than that in the acute hepatitis B patients. The IFNgamma and TNFalpha
      levels of acute severe hepatitis B patients were both significantly higher than
      those in the chronic severe hepatitis group (P less than 0.05). The ability to
      lyse target cells of HBV core 18-27 CTLs was also significantly higher in the
      acute severe hepatitis B group than that in the chronic severe hepatitis B group
      (P less than 0.05). CONCLUSION: The response to antigen stimulation was much
      higher in acute severe hepatitis B than in chronic severe hepatitis B patients.
      The specific CTLs persisted among the peripheral blood mononuclear cells in acute
      severe hepatitis B, which may be related to the viral clearance.

PMID- 16995979
TI  - [Inhibition of HBV replication and antigen expression by RNA interference against
      different targets].
AB  - OBJECTIVES: To observe the inhibition of HBV replication and antigen expression
      by RNA interference aimed at different parts of the HBV genome. METHODS:
      Following the rules of shRNA expression vector design and construction, we
      constructed seven kinds of sequence specific vectors and two kinds of mutant
      shRNA expression ones. We then cotransfected those shRNA and HBV expression
      vectors into HepG2 cells using lipofectamine2000. The level of HBV replication
      was investigated using Southern blot and the antigen expression using ELISA.
      RESULTS: The replication of HBV DNA was inhibited by many shRNAs, especially the
      ones against P1, S2, C2, S1 and X. The inhibition rate against P1 was as high as
      95%. Results obtained with ELISA showed that the shRNAs targeting C2, C1 and S2
      had high rates of inhibition to HBsAg. CONCLUSION: The replication and antigen
      expression of HBV could be inhibited by shRNAs aimed at four different open read
      frames, and higher inhibition rates of HBV replication and surface antigen
      expression could be obtained by P1 and C2, respectively.

PMID- 16995980
TI  - [The construction and primary screening of a phage display library of HCV C and
      E1 genes evolved with an artificial pattern].
AB  - OBJECTIVES: To construct and screen a primarily phage display library of HCV C
      and E1 genes evolved with an artificial pattern. METHODS: Two genes of about 1 kb
      with different genotypes were evolved by DNA shuffling. The re-assembled HCV C
      and E1 genes were cloned into a phage vector. After being rescued with helper
      phage M13KO7, a phage display library was constructed. Then the library was
      screened with anti-C and E1 McAb. Double-antibody sandwich enzyme-linked
      immunosorbent assay (DAS-ELISA) was carried out on twenty individual phage clones
      selected randomly to detect their binding and reactive activity with high-titer
      HCV-positive sera. Normal sera were used as controls. RESULTS: The phage display
      library of HCV C and E1 genes which evolved with an artificial pattern was
      constructed. Their capacity amounted to 1.64 x 10(6), and 86 percent of the
      clones contained C and E1 genes. After four rounds of panning, the phage library
      was specifically enriched. Twelve positive clones were successfully screened.
      CONCLUSION: The capacity and diversity of the constructed library are enough for
      screening. The results demonstrate the superiority of the specific binding and
      reactive activity and affinity of the 12 phage clones from the HCV positive sera.

PMID- 16995981
TI  - [Adenovirus vector expressing MDA-7/IL-24 selectively induces growth arrests and
      apoptosis in human hepatocellular carcinoma cell lines independent of the state
      of p53 gene].
AB  - OBJECTIVE: To investigate the effect of melanoma differentiation associated gene
      7/interleukin 24 (MDA/IL-24) on human hepatocellular carcinoma cell lines HepG2,
      MHCC97L and Hep3B and normal liver cell line L02 with a different p53 state.
      METHODS: The MDA-7/IL-24 gene was transfected into human hepatocellular carcinoma
      cell lines HepG2, MHCC97L and Hep3B and hepatocyte line L02 with a replication
      incompetent adenovirus vector. The mRNA expression of MDA7/IL-24 in HepG2,
      MHCC97L, Hep3B and L02 cells was confirmed using RT-PCR. Protein expression was
      confirmed using ELISA assay. MTT assay and flow cytometry were used to study
      tumor cell proliferation and cell cycle in vitro. Hoechst and flow cytometry
      assay after annexin-V and PI staining were performed to indicate the apoptosis
      effect. RESULTS: Exogenous MDA-7/IL-24 gene was expressed in HepG2, MHCC97L,
      Hep3B and L02 cells. The protein product of MDA-7/IL-24 was confirmed in the
      supernatant. MTT assay and apoptosis test indicated MDA-7/IL-24 could induce
      growth suppression and apoptosis of HepG2, MHCC97L and Hep3B but could not in
      L02. Cell cycle test revealed MDA-7/IL-24 could block those cancer cells in G2/M
      but not in the normal cell L02. CONCLUSION: MDA-7/IL-24 selectively induces
      growth suppression and apoptosis in hepatocellular carcinoma lines HepG2, MHCC97L
      and Hep3B in vitro independent of the state of p53 gene but not in normal liver
      cell L02. This indicates MDA-7/IL-24 can be a perfect gene for gene therapy in
      hepatocellular carcinoma.

PMID- 16995983
TI  - [Clinical application of artificial livers].

PMID- 16995982
TI  - [A relationship between cyclooxygenase-2 expression and tumor angiogenesis in
      experimental rat liver carcinogenesis].
AB  - OBJECTIVE: To explore the relationship between the expression of cyclooxygenase-2
      (COX-2) and angiogenesis in hepatocellular carcinoma. METHODS: Forty Wistar rats
      were divided into two groups: a model group (30 rats) and a normal group (10
      rats). Hepatocellular carcinoma was induced with 0.01% diethylnitrosamine (DEN)
      in the model group rats. The rats were sacrificed in batches at the 6th, 12th and
      18th week of the experiment. Histological sections of liver tissues were made
      using routine methods. The expressions of COX-2, VEGF, VEGFR-2/KDR, and MMP-2
      protein in the liver tissues were evaluated using immunohistochemical methods.
      RESULTS: In liver sections from the model group there were marked pathological
      changes (steatosis, cell infiltration, cirrhosis and liver cancer). The
      expressions of VEGF, VEGFR-2/KDR, and MMP-2 in those liver tissues were
      remarkably increased during the hepatocellular carcinogenesis. Microvessel
      density (MVD) was also obviously raised during the process of the cancer
      development. There was a direct correlation between the MVD and VEGF/KDR/MMP-2
      (r=0.858, 0.788, 0.684, respectively; all P less than 0.01). There was also a
      direct correlation between the COX-2 and VEGF/KDR/MMP-2/MVD (r=0.771, 0.599,
      0.690, 0.788, respectively; all P < 0.01). CONCLUSION: COX-2 can promote tumor
      angiogenesis during rat hepatocellular carcinogenesis. This may be one of the
      mechanisms in which COX-2 promotes carcinomas.

PMID- 16995984
TI  - [Comments on the current status of the clinical application of artificial
      livers].

PMID- 16995985
TI  - [A case of primary hepatic amyloidosis with factor X deficiency].

PMID- 16995986
TI  - [Problems and strategies in the application of artificial livers].

PMID- 16995987
TI  - [Current status in the use of artificial liver support systems for treating
      fulminant hepatic failure].

PMID- 16995988
TI  - [To evaluate the effects of orthotopic liver transplantation in the treatment of
      fulminating hepatitis].

PMID- 16995989
TI  - [Severe viral hepatitis complicated with pleural aspergillus infection treated
      with itraconazole and amphotericin B].

PMID- 16995990
TI  - [Effect of TGFbeta1 vaccine on the expression of MMP-2 and TIMP-2 in rats with
      liver fibrosis].

PMID- 16995991
TI  - [Plasma proteomic pattern predicts the stages of rat liver fibrosis].

PMID- 16995992
TI  - [Expression and significance of transforming growth factor beta receptor I and
      platelet derived growth factor and their receptors in liver tissues of patients
      with non-alcoholic fatty liver].

PMID- 16995993
TI  - [Preventive effects of pioglitazone on rat fatty liver induced by a high fat
      diet].

PMID- 16995994
TI  - [Effect of rosiglitazone on metalloproteinase tissue inhibitor-1 in CCl4-induced
      liver fibrosis in rats].

PMID- 16995995
TI  - [The significance of anti-endothelial cell antibody expression in rat liver
      fibrosis treated with estrogen].

PMID- 16995996
TI  - [The effect of radiofrequency ablation combined with arsenites on rabbit liver
      VX2 tumors].

PMID- 16995997
TI  - [Ganglioside GD3 enhances the anti-tumor effect of doxorubicin on hepatoma
      cells].

PMID- 16995998
TI  - [Effect of saikosaponins-d on cyclooxygenase-2 expression of human hepatocellular
      carcinoma cell line SMMC-7721].

PMID- 16995999
TI  - [Insulin-like growth factor binding proteins and endotoxin in liver fibrosis].

PMID- 16996000
TI  - [A case of angiosarcoma developed from liver hamartomas].

PMID- 16996001
TI  - [High mobility group box 1 protein and its effect on liver injury complicated
      with endotoxemia].

PMID- 16996002
TI  - Transplanted human umbilical cord blood mononuclear cells improve left
      ventricular function through angiogenesis in myocardial infarction.
AB  - BACKGROUND: Human umbilical cord blood contains an abundance of immature
      stem/progenitor cells, which may participate in the repair of hearts that have
      been damaged by myocardial infarction (MI). This study aimed to evaluate the
      effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation
      on cardiac function and left ventricular remodeling in rat model of MI. METHODS:
      Forty-five male Wistar rats were randomized into three groups: MI or control
      group (n = 15), MI plus cell transplantation (n = 15), and sham group (n = 15).
      Acute myocardial infarction (AMI) was established by ligating the left anterior
      descending artery, thereafter, hUCBC were implanted into the marginal area of
      infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC
      following the same protocol. Left ventricular function assessment was carried out
      by echocardiography and invasive hemodynamic measurements one month post MI. All
      rats were sacrificed for histological and immunochemical examinations. RESULTS:
      The transplanted hUCBC survived and engaged in the process of myocardial repair
      in the host heart. Echocardiography demonstrated that left ventricular function
      improved significantly in the rats that underwent cell transplantation.
      Hemodynamic studies found a significantly decreased left ventricular end
      diastolic pressure (LVEDP) [(21.08 +/- 8.10) mmHg vs (30.82 +/- 9.59) mmHg, P <
      0.05], increase in +dp/dt(max) [(4.29 +/- 1.27) mmHg/ms vs (3.24 +/- 0.75)
      mmHg/ms, P < 0.05), and increase in -dp/dt(max) [(3.71 +/- 0.79) mmHg/ms vs (3.00
      +/- 0.49) mmHg/ms, P < 0.05] among MI group with hUCBC transplantation when
      compared with MI/control group. Masson's trichrome staining revealed that the
      collagen density in the left ventricle was significantly lower in rats of
      transplantation group than that in the MI control groups [(6.33 +/- 2.69)% vs
      (11.10 +/- 3.75)%, P < 0.01]. Based on immunostaining of alpha-actin, the numbers
      of microvessels were significantly (P < 0.01) increased at the boundary of
      infarction site. Similarly higher mRNA expression of vascular endothelial growth
      factor (VEGF) 164 and VEGF188 were found at 7- and 28-day post cell
      transplantation in MI group with hUCBC transplantation when compared with
      MI/control group. CONCLUSIONS: Transplanted hUCBC can survive in host myocardium
      without immunorejection, significantly improve left ventricular remodeling after
      AMI and promote a higher level of angiogenesis in the infarct zones. All these
      factors beneficially affect cardiac repair in the setting of MI. Therefore human
      umbilical cord blood may be potential source for cell-based therapy for AMI.

PMID- 16996003
TI  - Short-term effect of cardiac resynchronization therapy in patients with ischaemic
      or nonischaemic cardiomyopathy.
AB  - BACKGROUND: Patients with heart failure were candidates for cardiac
      resynchronization therapy (CRT) regardless of underlying aetiology. This study
      observed the effect of CRT in patients with ischaemic or nonischaemic
      cardiomyopathy. METHODS: One hundred and forty-two patients with refractory
      chronic heart failure and left bundle branch block received cardiac
      resynchronization therapy, 91 men and 51 women, average age 60 years. Left
      ventricular ejection fraction (LVEF) was severely depressed (mean 29%), left
      ventricular end diastolic diameter (LVEDD) enlarged (mean 72 mm) and QRS width
      was lengthened (mean 147 ms). Ninety-eight had nonischaemic cardiomyopathy and 44
      had ischaemic cardiomyopathy. RESULTS: After cardiac resynchronization therapy,
      the heart function was significantly improved. The mean LVEF increased from 29%
      to 36% after pacing. In patients with nonischaemic cardiomyopathy, the LVEF was
      improved from 28% to 37%, and in patients with ischaemic cardiomyopathy, the LVEF
      was improved from 30% to 36%. No significant difference of the improvement was
      found between the two groups (P > 0.05). CONCLUSIONS: Cardiac resynchronization
      therapy could significantly improve cardiac function in patients with chronic
      heart failure regardless of the underlying heart disease.

PMID- 16996004
TI  - Effect of platelet-rich plasma in the treatment of periodontal intrabony defects
      in humans.
AB  - BACKGROUND: Platelet-rich plasma (PRP) is a kind of natural source of autologous
      growth factors, and has been used successfully in medical community. However, the
      effect of PRP in periodontal regeneration is not clear yet. This study was
      designed to evaluate the effectiveness of PRP as an adjunct to bovine porous bone
      mineral (BPBM) graft in the treatment of human intrabony defects. METHODS:
      Seventeen intrabony defects in 10 periodontitis patients were randomly treated
      either with PRP and BPBM (test group, n = 9) or with BPBM alone (control group, n
      = 8). Clinical parameters were evaluated including changes in probing depth,
      relative attachment level (measured by Florida Probe and a stent), and bone
      probing level between baseline and 1 year postoperatively. Standardized
      periapical radiographs of each defect were taken at baseline, 2 weeks, and 1 year
      postoperatively, and analyzed by digital subtraction radiography (DSR). RESULTS:
      Both treatment modalities resulted in significant attachment gain, reduction of
      probing depth, and bone probing level at 1-year post-surgery compared to
      baseline. The test group exhibited statistically significant improvement compared
      to the control sites in probing depth reduction: (4.78 +/- 0.95) mm versus (3.48
      +/- 0.41) mm (P < 0.01); clinical attachment gain: (4.52 +/- 1.14) mm versus
      (2.85 +/- 0.80) mm (P < 0.01); bone probing reduction: (4.56 +/- 1.04) mm versus
      (2.88 +/- 0.79) mm (P < 0.01); and defect bone fill: (73.41 +/- 14.78)% versus
      (47.32 +/- 11.47)% (P < 0.01). DSR analysis of baseline and 1 year
      postoperatively also showed greater radiographic gains in alveolar bone mass in
      the test group than in the control group: gray increase (580 +/- 50) grays versus
      (220 +/- 32) grays (P = 0.0001); area with increased gray were (5.21 +/- 1.25)
      mm(2) versus (3.02 +/- 1.22) mm(2) (P = 0.0001). CONCLUSIONS: The treatment with
      a combination of PRP and BPBM led to a significantly favorable clinical
      improvement in periodontal intrabony defects compared to using BPBM alone.
      Further studies are necessary to assess the long-term effectiveness of PRP, and a
      larger sample size is needed.

PMID- 16996005
TI  - Associated risk factors of knee osteoarthritis: a population survey in Taiyuan,
      China.
AB  - BACKGROUND: Since knee osteoarthritis (KOA) is one of the common diseases,
      identification of its associated risk factors is of preventive significance. This
      investigation was designed to investigate the prevalence of KOA in Taiyuan, and
      identify the associated risk factors of KOA. METHODS: A population sample was
      surveyed of 2188 adults aged from 35 to 64 years, living in 6-story buildings
      without elevators. The protocol of Asia Pacific League of Associations for
      Rheumatology (APLAR) Community Oriented Program for Control of Rheumatic Diseases
      (COPCORD) core questionnaire was implemented. The data on knee pain and KOA were
      collected and analyzed. Variables such as sex, age, body mass index (BMI), waist
      circumference (WC), education level, and smoking history, were included in binary
      logistic regression model for further analysis. RESULTS: The prevalence rates of
      knee pain and KOA were 13.6% and 10.9%, respectively, significantly higher than
      those in Shantou of south China and similar to those in Beijing of north China.
      The prevalence of KOA was significantly higher in women than in men (18.3% versus
      8.7% and 15.1% versus 6.3%), with a tendency of increase with age. The prevalence
      was increased more obviously in women after 40 years old and in men after 45
      years old. BMI in KOA group was significantly higher than that in non-KOA group.
      Binary Logistic regression revealed that age, sex, and BMI were significantly
      associated with KOA, whereas no significant correlation was seen between KOA and
      other factors such as climbing stairs, WC, time length of occupation service,
      education level, smoking history and religious belief. CONCLUSION: Geography,
      age, sex, and BMI might be the risk factors of KOA, but climbing stairs, WC, time
      length of occupation service, education level, smoking history and religious
      belief are not correlated with KOA. Prevention of KOA should be initiated before
      the middle-age, especially in female adults, and weight control is necessary.
      Other factors might also contribute to the development of KOA, but further study
      is needed to elucidate the role of these factors.

PMID- 16996006
TI  - Neuronavigator-guided percutaneous radiofrequency thermocoagulation in the
      treatment of intractable trigeminal neuralgia.
AB  - BACKGROUND: Percutaneous radiofrequency thermocoagulation of the trigeminal
      ganglion (PRTTG) is regarded as the first choice for most patients with
      trigeminal neuralgia (TN) because of its safety and feasibility. However,
      neuronavigator-guided PRTTG has been seldom reported. The purpose of this study
      was to assess the safety and efficacy of neuronavigator-guided PRTTG for the
      treatment of intractable TN. METHODS: Between January 2000 and December 2004, 54
      patients with intractable TN were enrolled into this study and were randomly
      divided into two groups. The patients in navigation group (n = 26) underwent
      PRTTG with frameless neuronavigation, and those in control group (n = 28)
      received PRTTG without neuronavigation. Three months after the operation, the
      efficacy, side effects, and complications of the surgery were recorded. The
      patients in the control group were followed up for 10 to 54 months (mean, 34 +/-
      5), and those in the navigation group were followed up for 13 to 58 months (mean,
      36 +/- 7). Kaplan-Meier analyses of the pain-free survival curves were used for
      the censored survival data, and the log-rank test was used to compare survival
      curves of the two groups. RESULTS: The immediate complete pain-relief rate of the
      navigation group was 100%, whereas it was 95% in the control. The proportion of
      sustained pain-relief rates at 12, 24 and 36 months after the procedure were 85%,
      77%, and 62% in the navigation group, and 54%, 40%, and 35% in the control.
      Recurrences in the control group were more common than that in the navigation
      group. Annual recurrence rate in the first and second years were 15% and 23% in
      the navigation group, and 46%, 60% in the control group. No side-effect and
      complication was noted in the navigation group except minimal facial hypesthesia.
      CONCLUSION: Neuronavigator-guided PRTTG is a safe and promising method for
      treatment of intractable TN with better short- and long-term outcomes and lower
      complication rate than PRTTG without neuronavigation.

PMID- 16996008
TI  - Effects of lower fluence pulsed dye laser irradiation on production of collagen
      and the mRNA expression of collagen relative gene in cultured fibroblasts in
      vitro.
AB  - BACKGROUND: Lower fluence of 585-nm flashlamp-pumped pulsed dye laser has been
      successfully used as a nonablative technique in the treatment of wrinkles. The
      objective of this study was to evaluate the effect of the pulsed dye laser (585
      nm) on the production of collagen and the mRNA expression of collagen related
      gene in fibroblasts in vitro. METHODS: Cultured fibroblasts were treated with a
      585-nm flashlamp-pumped pulsed dye laser (fluence 3 J/cm(2), 4 J/cm(2), spot size
      7 mm, pulse duration 450 micros). The production of collagen and the mRNA
      expression of transforming growth factor (TGF)-beta1, SMAD2, SMAD3, SMAD4, SMAD7
      and type I procollagen alpha1, alpha2 in fibroblasts were investigated by
      colorimetry or real time polymerase chain reaction. RESULTS: The production of
      collagen was significantly up-regulated after treatment with a 585-nm flashlamp
      pumped pulsed dye laser with a fluence of 3 J/cm(2) (P < 0.001). The mRNA
      expression of TGF-beta1, SMAD2, SMAD3, SMAD4, SMAD7 and procollagen I was
      significantly up-regulated after treatment with a 585-nm flashlamp-pumped pulsed
      dye laser with a fluence of 3 J/cm(2) (P < 0.001). No significant difference of
      mRNA expression of SMAD2, SMAD3, SMAD4, SMAD7 and type I procollagen was found
      between controls and fibroblasts treated with pulsed dye laser with a fluence of
      4 J/cm(2) (P > 0.05). CONCLUSIONS: Lower fluence (3 J/cm(2)) pulsed dye laser
      increased the collagen production in fibroblasts by up-regulating TGF-beta1,
      SMAD2, SMAD3, SMAD4, SMAD7 and type I procollagen mRNA expression. These may be
      the reason it can be effectively used in the treatment of wrinkles.

PMID- 16996007
TI  - Effect of proline rich domain of an RNA-binding protein Sam68 in cell growth
      process, death and B cell signal transduction.
AB  - BACKGROUND: Sam68 plays an important role as a multiple functional RNA binding
      nuclear protein in cell cycle progress, RNA usage, signal transduction, and
      tyrosine phosphorylation by Src during mitosis. However, its precise impact on
      these essential cellular functions remains unclear. The purpose of this study is
      to further elucidate Sam68 functions in RNA metabolism, signal transduction
      regulation of cell growth and cell proliferation in DT40 cell line. METHODS: By
      using gene targeting method, we isolated a mutation form of Sam68 in DT40 cells
      and described its effect on cell growth process and signal transduction.
      Southern, Northern, and Western blot, phosphorylation and flow-cytometric
      analyses were performed to investigate the Sam68 functions. RESULTS: A slower
      growth rate (2.1 hours growth elongation) and longer S phase (1.7 hours
      elongation) was observed in the Sam68 mutant cells. Serum depletion resulted in
      increased amounts of dead cells, and expansion of S phase in mutant cells. Upon B
      cell cross-linking, the maximal level of tyrosine phosphorylation on BLNK was
      observed to be significantly lower in mutant cells. CONCLUSIONS: The proline rich
      domain of Sam68 is involved in cell growth control by modulating the function of
      mRNAs in S phase or earlier and the functions as an adaptor molecule in B cell
      signal transduction pathways.

PMID- 16996009
TI  - Auditory cortical responses evoked by pure tones in healthy and sensorineural
      hearing loss subjects: functional MRI and magnetoencephalography.
AB  - BACKGROUND: Blood oxygen level dependent functional magnetic resonance imaging
      (fMRI) and magnetoencephalography are new techniques of brain functional imaging
      which can provide the information of excitation of neurons by measure the changes
      of hemodynamics and electrophysiological data of local brain tissue. The purpose
      of this study was to study functional brain areas evoked by pure tones in healthy
      and sensorineural hearing loss subjects with these techniques and to compare the
      differences between the two groups. METHODS: Thirty healthy and 30 sensorineural
      hearing loss subjects were included in this study. In fMRI, block-design paradigm
      was used. During the active epoch the participants listened to 1000 Hz, sound
      pressure level 140 dB pure tones at duration 500 ms, interstimulus interval 1000
      ms, which presented continuously via a magnetic resonance-compatible audio
      system. None stimulus was executed in control epoch. In magnetoencephalography
      study, every subject received stimuli of 1000 Hz tone bursts delivered to the
      bilateral ear at duration 8 ms, interstimulus intervals 1000 ms. Sound pressure
      level in healthy subjects was 30 dB; in sensorineural hearing loss subjects was
      20 dB above everyone's hearing threshold respectively. All subjects were examined
      with 306-channel whole-scalp neuromagnetometer. RESULTS: In fMRI, all subjects
      showed significant activations in bilateral Heschl's gyri, anterior pole of
      planum temporale, planum temporale, precentral gyri, postcentral gyri,
      supramarginal gyri, superior temporal gyri, inferior frontal gyri, occipital
      lobes and cerebellums. The healthy subjects had more intensive activation in
      bilateral Heschl's gyri, anterior pole of planum temporale, inferior frontal
      gyri, left superior temporal gyri and right planum temporale than the hearing
      loss subjects. But in precentral gyri, postcentral gyri and occipital lobes, the
      activation is more intensive in the hearing loss subjects. In
      magnetoencephalography study, both in the hearing loss and the healthy subjects,
      the most evident audio evoked fields activated by pure tone were N100m, which
      located precisely on the Heschl's gyrus. Compared with the hearing loss subjects,
      N100m of the healthy subjects was stronger and had longer latencies in right
      hemisphere. CONCLUSIONS: Under proper pure tone stimulus the activation of
      auditory cortex can be elicited both in the healthy and the sensorineural hearing
      loss subjects. Either at objective equivalent stimuli or at subjectively
      perceived equivalent stimuli, the auditory responses were more intensive in
      healthy subjects than hearing loss subjects. The tone stimuli were processed in a
      network in human brain and there was an intrinsic relation between the auditory
      and visual cortex. Blood oxygen level dependent fMRI and magnetoencephalography
      could reinforce each other.

PMID- 16996010
TI  - Effects of ketamine-midazolam anesthesia on the expression of NMDA and AMPA
      receptor subunit in the peri-infarction of rat brain.
AB  - BACKGROUND: Activation of N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3
      hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors play an important
      role in the neurons death induced by ischemia. The mitigating effect of
      intravenous anesthetics on ischemic neuron injury is related to their influence
      on NMDA receptors. This study was performed to investigate the effect of ketamine
      midazolam anesthesia on the NMDA and AMPA receptor subunits expression in the
      peri-infarction of ischemic rat brain and explore its potential mechanism of
      neuroprotection. METHODS: Thirty Sprague Dawley (SD) rats were subjected to
      permanent middle cerebral artery occlusion under ketamine/atropine (100/0.05
      mg/kg) or ketamine-midazolam/atropine (60/50/0.05 mg/kg) intraperitoneal
      anesthesia (n=15 each). Twenty-four hours after ischemia, five rats in each group
      were killed by injecting the above dosage of ketamine or ketamine-midazolam
      intraperitoneally and infarct size was measured. Twenty-four and 72 hours after
      ischemia, four rats in each group were killed by injecting the above dosage of
      ketamine or ketamine-midazolam intraperitoneally. After staining the brain tissue
      slices with toluidine blue, the survived neurons in the peri-infarction were
      observed. Also, the expression level of NMDA receptors 1 (NR1), NMDA receptors 2A
      (NR2A), NMDA receptors 2B (NR2B) and AMPA (GluR1 subunit) were determined by
      grayscale analysis in immunohistochemical stained slices. RESULTS: Compared with
      ketamine anesthesia, ketamine-midazolam anesthesia produced not only smaller
      infarct size [(24.1+/-4.6)% vs (38.4+/-4.2)%, P<0.05], but also higher neuron
      density (24 hours: 846+/-16 vs 756+/-24, P<0.05; 72 hours: 882+/-22 vs 785+/-18,
      P<0.05) and lower NR2A (24 hours: 123.0+/-4.9 vs 95.0+/-2.5, P<0.05; 72 hours:
      77.8+/-4.1 vs 54.2+/-3.9, P<0.05) and NR2B (24 hours: 98.5+/-2.7 vs 76.3+/-2.4,
      P<0.05; 72 hours: 67.2 +/-7.5 vs 22.2+/-2.6, P<0.05) expression level in the peri
      infarction following ischemia. CONCLUSION: The protective effects of ketamine
      midazolam anesthesia on ischemic brain injury may related to decreasing NR2A and
      NR2B expression.

PMID- 16996011
TI  - Measurement of liver function for patients with cirrhosis by 13C-methacetin
      breath test compared with Child-Pugh score and routine liver function tests.

PMID- 16996012
TI  - Effect of dexamethasone on the release of transforming growth factor-beta1,
      interleukin-8, interleukin-10 and RANTES release by sputum cells in severe
      asthma.

PMID- 16996013
TI  - Apoptosis of drug-resistant human ovarian carcinoma cell line COC1/DDP induced by
      survivin antisense oligonucleotides.

PMID- 16996014
TI  - Drug-eluting stents improve clinical outcomes in Chinese diabetic patients with
      de novo coronary artery disease.

PMID- 16996015
TI  - Q fever endocarditis with multi-organ complication: a case report.

PMID- 16996016
TI  - Pay more attention to the immunologically comparative evaluation of HIV-1 DNA
      vaccine in combination with adjuvant cytokines: a long way to go.

PMID- 16996017
TI  - The effect of distractions on the crash types of teenage drivers.
AB  - Teenage drivers are overrepresented in crashes when compared to middle-aged
      drivers. Driver distraction is becoming a greater concern among this group as in
      vehicle devices, opportunities for distractions, and teenage drivers' willingness
      to engage in these activities increase. The objective of this study was to
      determine how different distraction factors impact the crash types that are
      common among teenage drivers. A multinomial logit model was developed to predict
      the likelihood that a driver will be involved in one of three common crash types:
      an angular collision with a moving vehicle, a rear-end collision with a moving
      lead vehicle, and a collision with a fixed object. These crashes were evaluated
      in terms of four driver distraction categories: cognitive, cell phone related, in
      vehicle, and passenger-related distractions. Different driver distractions have
      varying effects on teenage drivers' crash involvement. Teenage drivers that were
      distracted at an intersection by passengers or cognitively were more likely to be
      involved in rear-end and angular collisions when compared to fixed-object
      collisions. In-vehicle distractions resulted in a greater likelihood of a
      collision with a fixed object when compared to angular collisions. Cell phone
      distractions resulted in a higher likelihood of rear-end collision. The results
      from this study need to be evaluated with caution due to the limited number of
      distraction related cases available in the U.S. GES crash database. Implications
      for identifying and improving the reporting of driver distraction related factors
      are therefore discussed.

PMID- 16996019
TI  - A homogeneous scintillation proximity assay for acetyl coenzyme A carboxylase
      coupled to fatty acid synthase.
AB  - We have devised a rapid and sensitive homogeneous assay for acetyl CoA
      carboxylase (ACC) in a scintillation proximity assay format suitable for high
      throughput screening. In this assay, ACC is coupled to fatty acid synthase (FAS).
      Malonyl CoA, the product of the ACC reaction, and acetyl CoA serve as substrates
      for FAS to synthesize palmitic acid. When [(3)H]acetyl CoA is used in the ACC/FAS
      coupled system, [(3)H]palmitic acid, the final product, is readily detected by
      scintillation proximity in a FlashPlate or Image FlashPlate coated with
      phospholipid. The [(3)H]palmitic acid binds to the coated phospholipid through
      hydrophobic interaction which brings it into close proximity of the scintillant
      on the FlashPlate or the Image FlashPlate, yielding photons that are read in a
      TopCount or LeadSeeker, respectively. The current assay consists of simple
      reagent addition, incubation, and detection of signal. The signal is
      approximately 30-fold over the background and the Z' value is approximately 0.80,
      suggesting that this assay is robust and highly reproducible. To our knowledge
      this ACC/FAS coupled scintillation proximity assay is the only assay format that
      is compatible with high-throughput screening for systematic search of inhibitors
      against mammalian ACC.

PMID- 16996018
TI  - A model of Leptospirosis infection in an African rodent to determine risk to
      humans: seasonal fluctuations and the impact of rodent control.
AB  - Human leptospirosis (Leptospira spp. infection) is a worldwide public health
      problem that is of greatest concern for humid tropical and subtropical regions.
      The magnitude of the problem in these areas is larger because of the climatic and
      environmental conditions the bacterium face outside their hosts but also because
      of the frequency of contacts between people and sources of infection. Rodents are
      thought to play the most important role in the transmission of human
      leptospirosis. We here model the dynamics of infection in an African rodent
      (Mastomys natalensis) that is thought to be the principal source of infection in
      parts of Tanzania. Our model, representing the climatic conditions in central
      Tanzania, suggests a strong seasonality in the force of infection on humans with
      a peak in the abundance of infectious mice between January and April in
      agricultural environments. In urban areas the dynamics are predicted to be more
      stable and the period of high numbers of infectious animals runs from February to
      July. Our results indicate that removal of animals by trapping rather than
      reducing the suitability of the environment for rodents will have the greater
      impact on reducing human cases of leptospirosis.

PMID- 16996020
TI  - DNA point mutation detection based on DNA ligase reaction and nano-Au
      amplification: a piezoelectric approach.
AB  - A novel piezoelectric method for DNA point mutation detection based on DNA ligase
      reaction and nano-Au-amplified DNA probes is proposed. A capture probe was
      designed with the potential point mutation site located at the 3' end and a thiol
      group at the 5' end to be immobilized on the gold electrode surface of quartz
      crystal microbalance (QCM). Successive hybridization with the target DNA and
      detection probe of nano-Au-labeled DNA forms a double-strand DNA (dsDNA). After
      the DNA ligase reaction and denaturing at an elevated temperature, the QCM
      frequency would revert to the original value for the target with single-base
      mismatch, whereas a reduced frequency response would be obtained for the case of
      the perfect match target. In this way, the purpose of point mutation
      discrimination could be achieved. The current approach is demonstrated with the
      identification of a single-base mutation in artificial codon CD17 of the beta
      thalassemia gene, and the wild type and mutant type were discriminated
      successfully. The scanning electron microscope (SEM) image showing that plenty of
      gold nanoparticles remained on the electrode surface demonstrated that the nano
      Au label served as an efficient signal amplification agent in QCM assay. A
      detection limit of 2.6 x 10(-9)mol/L of oligonucleotides was achieved. Owing to
      its ease of operation and low detection limit, it is expected that the proposed
      procedure may hold great promise in both research-based and clinical genomic
      assays.

PMID- 16996021
TI  - Magnetic circular dichroism of hemoproteins with in situ control of
      electrochemical potential: "MOTTLE".
AB  - Hemoproteins have been recognized for nearly a century and are ubiquitous
      components of cellular organisms. Despite our familiarity with these proteins,
      defining the functional role of a given heme can still present considerable
      challenges. In this situation, magnetic circular dichroism (MCD) is a technique
      of choice because it has the capacity to define heme oxidation, spin, and
      ligation states in solution and at ambient temperature. Unfortunately, the
      resolving power of MCD rarely has been brought to bare on the intermediate redox
      states accessible to multiheme proteins. This is due in large part to the time
      consuming procedure of magnetic field cycling required each time a sample is
      introduced into the magnet and the risk that control over, and knowledge of, the
      potential will be lost between sample preparation and spectral acquisition. Here
      we present a solution to this problem in the form of MCD-compatible optically
      transparent thin-layer electrochemistry (MOTTLE). MOTTLE defines redox behavior
      for cytochrome c in good agreement with the literature. In addition, MOTTLE
      reproduces the redox-driven transformation of heme ligand sets reported for
      cytochrome bd. Thus, MOTTLE provides a robust analytical tool for the dissection
      of heme properties with resolution across the electrochemical potential domain.

PMID- 16996022
TI  - Determination of daunomycin at a novel COOH/indium tin oxide ion implantation
      modified electrode.
AB  - A novel COOH+ ion implantation-modified indium tin oxide (COOH/ITO) electrode was
      prepared for the first time and applied for determination of daunomycin (or
      daunorubicin [DNR]). The electrode showed higher catalytic activity than bare ITO
      electrode with good reproducibility and stability. The determination condition of
      linear voltammetry was optimized. A calibration curve was obtained over the range
      2.0 x 10(-7) to 5.0 x 10(-6)mol/L, with a correlation coefficient of 0.9909 and a
      limit of detection of 1.0 x 10(-7)mol/L. The selectivity of the electrode was
      illustrated by determination of DNR in samples prepared of urine. X-ray
      photoelectron spectroscopy (XPS) analysis results showed that the implanted COOH+
      maintained characteristics of organic group -COOH. A field emission-scanning
      electron microscope (FSEM) result showed that the implanted surface caused
      defects and partial dislocations and formed many active centers.

PMID- 16996023
TI  - Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases.
AB  - Sphingolipids are ubiquitous components of cell membranes and their metabolites
      ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) have
      important physiological functions, including regulation of cell growth and
      survival. Cer and Sph are associated with growth arrest and apoptosis. Many
      stress stimuli increase levels of Cer and Sph, whereas suppression of apoptosis
      is associated with increased intracellular levels of S1P. In addition,
      extracellular/secreted S1P regulates cellular processes by binding to five
      specific G protein coupled-receptors (GPCRs). S1P is generated by phosphorylation
      of Sph catalyzed by two isoforms of sphingosine kinases (SphK), type 1 and type
      2, which are critical regulators of the "sphingolipid rheostat", producing pro
      survival S1P and decreasing levels of pro-apoptotic Sph. Since sphingolipid
      metabolism is often dysregulated in many diseases, targeting SphKs is potentially
      clinically relevant. Here we review the growing recent literature on the
      regulation and the roles of SphKs and S1P in apoptosis and diseases.

PMID- 16996024
TI  - Binding assays of inhibitors towards selected V-ATPase domains.
AB  - The macrolide antibiotic bafilomycin and the related synthetic compound SB 242784
      are potent inhibitors of the vacuolar H+ -ATPases (V-ATPase). It is currently
      believed that the site of action of these inhibitors is located on the membrane
      bound c-subunits of V-ATPases. To address the identification of the critical
      inhibitors binding domain, their specific binding to a synthetic peptide
      corresponding to the putative 4th transmembrane segment of the c-subunit was
      investigated using fluorescence resonance energy transfer (FRET), and for this
      purpose a specific formalism was derived. Another peptide of the corresponding
      domain of the c' isoform, was checked for binding of bafilomycin, since it is not
      clear if V-ATPase inhibition can also be achieved by interaction of the inhibitor
      with the c'-subunit. It was concluded that bafilomycin binds to the selected
      peptides, whereas SB 242784 was unable to interact, and in addition for
      bafilomycin, its interaction with the peptides either corresponding to the c- or
      the c'-subunit isoforms is identical. Since the observed interactions are however
      much weaker as compared to the very efficient binding of both bafilomycin and SB
      242784 to the whole protein, it can be concluded that assembly of all V-ATPase
      transmembrane segments is required for an efficient interaction.

PMID- 16996025
TI  - Intracellular trafficking of sphingolipids: relationship to biosynthesis.
AB  - The intracellular routes of sphingolipid trafficking are related to the
      compartmentalized nature of sphingolipid metabolism, with synthesis beginning in
      the endoplasmic reticulum, continuing in the Golgi apparatus, and degradation
      occurring mainly in lysosomes. Whereas bulk sphingolipid transport between
      subcellular organelles occurs primarily via vesicle-mediated pathways, evidence
      is accumulating that sphingolipids are found in subcellular organelles that are
      not connected to each other by vesicular flow, implying additional trafficking
      routes. After discussing how sphingolipids are transported through the secretory
      pathway, I will review evidence for sphingolipid metabolism in organelles such as
      the mitochondria, and then discuss how this impacts upon our current
      understanding of the regulation of intracellular sphingolipid transport.

PMID- 16996026
TI  - Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP
      10 expression.
AB  - Hormonal induction triggers a cascade leading to the expression of CCAAT/enhancer
      binding protein(C/EBP)alpha and peroxisome proliferator-activated receptor (PPAR)
      gamma, C/EBPalpha, and PPARgamma turns on series of adipocyte genes that give
      rise to the adipocyte phenotype. Previous findings indicate that C/EBPbeta, a
      transcriptional activator of the C/EBPalpha and PPARgamma genes, is rapidly
      expressed after induction, but lacks DNA-binding activity and therefore cannot
      activate transcription of the C/EBPalpha and PPARgamma genes early in the
      differentiation program. Acquisition of DNA-binding activity of C/EBPbeta occurs
      when CHOP-10, a dominant-negative form of C/EBP family members, is down-regulated
      and becomes hyperphosphorylated as preadipocytes traverse the G1-S checkpoint of
      mitotic clonal expansion. Evidences are presented in this report that
      lactacystin, a proteasome inhibitor, up-regulated the CHOP-10 expression, blocked
      the DNA-binding activity of C/EBPbeta, and subsequently inhibited MCE as well as
      adipocyte differentiation.

PMID- 16996027
TI  - Crosslinking of low-affinity glycoprotein ligands to galectin LEC-1 using a
      photoactivatable sulfhydryl reagent.
AB  - The N-terminal lectin domain (Nh) of the tandem repeat-type nematode galectin LEC
      1 has a lower affinity for sugars than the C-terminal lectin domain. To confirm
      that LEC-1 forms a complex with N-acetyllactosamine-containing glycoproteins, we
      used several mutants of LEC-1 in which a unique cysteine residue was introduced
      into the Nh domain and examined their binding to bovine asialofetuin with a
      photoactivatable sulfhydryl crosslinking reagent. A crosslinked product was
      formed with the Q38C mutant, strongly suggesting the low-affinity interaction of
      Nh with the glycoprotein could be detected with this system.

PMID- 16996028
TI  - Protection against CCl4-induced injury in liver by adenovirally introduced
      thioredoxin gene.
AB  - Antioxidation therapy is a promising strategy for treating or preventing
      oxidative stress-related liver diseases. The human thioredoxin (TRX) gene was
      inserted into an adenovirus vector (Adv-TRX), which was administered to mice. The
      mice were treated with 1 ml/kg CCl4 48 h after the infection. Blood samples were
      taken and the liver was excised 24 h after the CCl4 treatment. Serum ammonia,
      aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were
      determined, and liver sections were stained with hematoxylin and eosin. RT-PCR
      analysis showed that the introduced TRX gene was expressed only in the liver. Adv
      TRX decreased the serum ammonia, AST, and ALT levels. Hematoxylin-eosin staining
      indicated that the CCl4-induced injury was significantly prevented by the Adv-TRX
      infection. The gene delivery of TRX, which plays a central role in intracellular
      redox control, was shown to be effective in protecting the liver against
      oxidative stress-induced injury.

PMID- 16996029
TI  - The rat Tspy is preferentially expressed in elongated spermatids and interacts
      with the core histones.
AB  - The testis specific protein Y encoded (TSPY) gene is a tandemly repeated gene on
      the mammalian Y chromosome. It encodes several slightly variant proteins that
      harbor a conserved domain of approximately 170 amino acids, termed TSPY/SET/NAP1
      domain, capable of binding to cyclin B. The human TSPY is preferentially
      expressed in spermatogonia and to lesser extent in the spermatids. Although rat
      harbors a single functional Tspy gene on its Y chromosome, the human and rat
      genes differ in their expression patterns, suggesting that they might serve
      different or variant functions in the testis. Transcripts of rTspy were first
      detected in the testis of 28-day-old rats, at which time the first wave of
      meiotic division was occurring. The rTspy protein was initially detected in stage
      9 elongating spermatids and peaked at stage-13 spermatids in adult testis, but
      not in spermatogonia, unlike the expression pattern of the human TSPY gene. Using
      a GST pull-down assay, we demonstrated that rTspy could bind to the core histones
      H2A, H2B, H3, and H4. Rat Tspy co-localized with the histones in the cytoplasm of
      selected elongated spermatids. Our results suggest that the rTspy may play
      critical roles as a histone chaperone during maturation of the elongating
      spermatids in the rat testis.

PMID- 16996030
TI  - Monoubiquitylation of GGA3 by hVPS18 regulates its ubiquitin-binding ability.
AB  - GGAs (Golgi-localizing, gamma-adaptin ear domain homology, ADP-ribosylation
      factor (ARF)-binding proteins), constitute a family of monomeric adaptor proteins
      and are associated with protein trafficking from the trans-Golgi network to
      endosomes. Here, we show that GGA3 is monoubiquitylated by a RING-H2 type
      ubiquitin ligase hVPS18 (human homologue of vacuolar protein sorting 18). By in
      vitro ubiquitylation assays, we have identified lysine 258 in the GAT domain as a
      major ubiquitylation site that resides adjacent to the ubiquitin-binding site.
      The ubiquitylation is abolished by a mutation in either the GAT domain or
      ubiquitin that disrupts the GAT-ubiquitin interaction, indicating that the
      ubiquitin binding is a prerequisite for the ubiquitylation. Furthermore, the GAT
      domain ubiquitylated by hVPS18 no longer binds to ubiquitin, indicating that
      ubiquitylation negatively regulates the ubiquitin-binding ability of the GAT
      domain. These results suggest that the ubiquitin binding and ubiquitylation of
      GGA3-GAT domain are mutually inseparable through a ubiquitin ligase activity of
      hVPS18.

PMID- 16996031
TI  - Circadian clocks regulate adenylyl cyclase activity rhythms in human RPE cells.
AB  - Genes and components of the circadian clock may represent relevant drug targets
      for diseases involving circadian dysfunctions. By exploiting an established cell
      line derived from human retinal pigment epithelium (HRPE), the cell constituting
      the blood-retinal barrier that is essential to maintain the visual functions of
      the sensorineural retina, we showed serum-shock induction of rhythmic changes in
      forskolin-evoked adenylyl cyclase (AC) activity. In the presence of Ca2+ and
      protein kinase A, the forskolin-induced AC activity is significantly, but not
      completely inhibited, suggesting the involvement of both Ca2+-sensitive and Ca2+
      insensitive AC isoforms in the regulation of circadian rhythmicity in these
      cells. Semi-quantitative RT-PCR showed circadian profile in the expression of
      three AC isoforms, the Ca2+-inhibitable AC5 and AC6 and the Ca2+-insensitive AC7,
      and the clock genes hPer1 and hPer2. Our results demonstrate for the first time
      circadian rhythmicity in a human cell line, identifying the isoforms involved in
      the circadian profile of AC activity and showing a rhythmicity of the clock gene
      mRNA expression in these cells. Therefore, the results reported here provide
      evidence for an intertwine between AC/[Ca2+]i signalling pathways and Per genes
      in the HRPE circadian clockwork.

PMID- 16996032
TI  - Hepatocyte-derived fibrinogen-related protein-1 is associated with the fibrin
      matrix of a plasma clot.
AB  - In order to study the multiple functions of fibrinogen and fibrin, we are
      investigating which proteins bind to the fibrin matrix of a plasma clot by using
      a proteomic approach. Extracts from washed plasma clots were analysed by 2-D gel
      electrophoresis. A relatively abundant spot was identified as hepatocyte-derived
      fibrinogen-related protein-1 (HFREP-1) by MALDI-TOF analysis, molecular mass (34
      kDa), iso-electric point (pI 5.5) as well as by Western blot analysis. HFREP-1 in
      plasma almost completely bound to the fibrin matrix during clot formation.
      Several purified fibrinogen preparations proved to be contaminated with HFREP-1.
      It is concluded that HFREP-1 (also named hepassocin), a protein with liver cell
      growth regulatory properties, occurs in plasma and strongly associates with
      fibrin and possibly fibrinogen.

PMID- 16996033
TI  - The phenylic hydroxyl group is essential for the induction of stress response by
      sodium salicylate.
AB  - We have shown that sodium salicylate (SA) activates the heat shock promoter and
      induces the expression of heat shock proteins (Hsps) with a concomitant increase
      in the thermotolerance of cells. To identify the functional groups of SA
      necessary for the induction of Hsps, we evaluated the effect of various
      derivatives of SA using a mammalian cell line containing a reporter gene
      downstream of an hsp105 promoter. Among the derivatives, the compounds in which
      the carboxyl group of SA was substituted activated the hsp105 promoter at 37
      degrees C as SA did, but the compounds in which the hydroxyl group was
      substituted did not. Thus, the phenylic hydroxyl group but not the carboxyl group
      of SA seemed to be necessary for a stress-induced response. In addition, the
      orientation of two functional groups on the benzene ring of SA derivatives was
      also important for the induction of a response. Among these compounds,
      salicylalcohol which strongly induced the expression of Hsps suppressed the
      protein aggregation and apoptosis caused by an expanded polyglutamine tract in a
      cellular model of polyglutamine disease. These findings may aid in the
      development of novel effective Hsp-inducers.

PMID- 16996034
TI  - Quercetin, a flavonoid, inhibits proliferation and increases osteogenic
      differentiation in human adipose stromal cells.
AB  - Flavonoids, which have been detected in a variety of foods, have been repeatedly
      reported to affect bone metabolism. However, the effects of flavonoids on
      osteoblastogenesis remain a matter of some controversy. In this study, the
      effects of quercetin on the differentiation and proliferation of human adipose
      tissue-derived stromal cells (hADSC) were determined. Quercetin was found to
      increase osteogenic differentiation in a dose-dependent manner. Other flavonoids,
      chrysin and kaempferol, were also shown to increase the osteogenic
      differentiation of hADSC, but this stimulatory effect was weaker than that
      associated with quercetin. Quercetin pretreatment administered prior to the
      induction of differentiation also exerted stimulatory effects on the osteogenic
      differentiation of hADSC. RT-PCR and real time PCR analysis showed that quercetin
      treatment induced an increase in the expression of osteopontin, BMP2, alkaline
      phosphatase and Runx2. Quercetin inhibited the proliferation of hADSC, but did
      not affect their survival. The pretreatment of quercetin increased ERK
      phosphorylation during osteogenic differentiation, although it did not increase
      ERK activity in control culture condition. ICI182780, an specific estrogen
      receptor antagonist, failed to inhibit the effects of quercetin on osteogenic
      differentiation. Quercetin-pretreated hADSC showed better bone regenerating
      ability in skull defect model of nude mice than naive cells. Our findings
      indicate that quercetin enhances osteogenic differentiation via an independent
      mechanism from estrogen receptor (ER) activation, and prove useful for in vivo
      bone engineering, using human mesencymal stem cells (hMSC).

PMID- 16996035
TI  - The combined use of non-radioactive in situ hybridization and real-time RT-PCR to
      assess gene expression in cryosections.
AB  - Gene expression changes in pathophysiological states can be spatiotemporally
      monitored by in situ hybridization and reliably quantified by real-time RT-PCR.
      Here we developed a new method whereby adjacent slides of frozen sections can be
      used for gene expression analysis by in situ hybridization and real-time RT-PCR.
      We applied this method to assess the mRNA expression of connexin 43 (Cx43), the
      major astrocytic connexin, after kainate-induced seizures in rat hippocampus. Gap
      junction-building connexins play a role in the pathogenesis of several diseases
      of the brain, including epilepsy. The number of Cx43 mRNA-positive cells in the
      hippocampus of kainate-treated and control rats was automatically quantified by
      computerized image analysis of brain sections hybridized with DIG-labeled RNA
      probes. In parallel, real-time RT-PCR was used to examine the relative Cx43 mRNA
      levels in hippocampal tissue from adjacent brain sections. Applying these two
      very sensitive methods we showed that kainate induced seizures do not affect
      hippocampal connexin 43 mRNA expression.

PMID- 16996036
TI  - Elevated lactate suppresses neuronal firing in vivo and inhibits glucose
      metabolism in hippocampal slice cultures.
AB  - Glucose is well accepted as the major fuel for neuronal activity, while it
      remains controversial whether lactate also supports neural activity. In
      hippocampal slice cultures, synaptic transmission supported by glucose was
      reversibly suppressed by lactate. To test whether lactate had a similar
      inhibitory effect in vivo, lactate was perfused into the hippocampi of
      unanesthetized rats while recording the firing of nearby pyramidal cells. Lactate
      perfusion suppressed pyramidal cell firing by 87.5+/-8.3% (n=6). Firing
      suppression was slow in onset and fully reversible and was associated with
      increased lactate concentration at the site of the recording electrode. In vivo
      suppression of neural activity by lactate occurred in the presence of glucose;
      therefore we tested whether suppression of neural firing was due to lactate
      interference with glucose metabolism. Competition between glucose and lactate was
      measured in hippocampal slice cultures. Lactate had no effect on glucose uptake.
      Lactate suppressed glucose oxidation when applied at an elevated, pathological
      concentration (10 mM), but not at its physiological concentration (1 mM).
      Pyruvate (10 mM) also inhibited glucose oxidation but was significantly less
      effective than lactate. The greater suppressive effect of lactate as compared to
      pyruvate suggests that alteration of the NAD(+)/NADH ratio underlies the
      suppression of glucose oxidation by lactate. ATP in slice culture was unchanged
      in glucose (1 mM), but significantly reduced in lactate (1 mM). ATP in slice
      culture was significantly increased by combination of glucose (1 mM) and lactate
      (1 mM). These data suggest that alteration of redox ratio underlies the
      suppression of neural discharge and glucose metabolism by lactate.

PMID- 16996037
TI  - Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB
      expression in the rat hippocampus.
AB  - The heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is an analog of the
      adrenocorticotropin fragment (4-10) which after intranasal application has
      profound effects on learning and exerts marked neuroprotective activities. Here,
      we found that a single application of Semax (50 microg/kg body weight) results in
      a maximal 1.4-fold increase of BDNF protein levels accompanying with 1.6-fold
      increase of trkB tyrosine phosporylation levels, and a 3-fold and a 2-fold
      increase of exon III BDNF and trkB mRNA levels, respectively, in the rat
      hippocampus. Semax-treated animals showed a distinct increase in the number of
      conditioned avoidance reactions. We suggest that Semax affects cognitive brain
      functions by modulating the expression and the activation of the hippocampal
      BDNF/trkB system.

PMID- 16996038
TI  - Genetic interactions among cortical malformation genes that influence
      susceptibility to convulsions in C. elegans.
AB  - Epilepsy is estimated to affect 1-2% of the world population, yet remains poorly
      understood at a molecular level. We have previously established the roundworm
      Caenorhabditis elegans as a model for investigating genetic susceptibilities to
      seizure-like convulsions in vivo. Here we investigate the behavioral consequences
      of decreasing the activity of nematode gene homologs within the LIS1 pathway that
      are associated with a human cortical malformation termed lissencephaly.
      Bioinformatic analysis revealed the nud-2 gene, encoding the worm homolog of
      mammalian effectors of LIS1, termed NDE1 and NDEL1. Phenotypic analysis of
      animals targeted by RNA interference (RNAi) was performed using a
      pentylenetetrazole (PTZ) exposure paradigm to induce convulsions. Worms depleted
      for LIS1 pathway components (NUD-1, NUD-2, DHC-1, CDK-5, and CDKA-1) exhibited
      significant convulsions following PTZ and RNAi treatment. Strains harboring
      fluorescent markers for GABAergic neuronal architecture and synaptic vesicle
      trafficking were employed to discern putative mechanisms accounting for observed
      convulsion behaviors. We found that depletion of LIS1 pathway components resulted
      in defective GABA synaptic vesicle trafficking. We also utilized combinations of
      specific genetic backgrounds to create a sensitized state for convulsion
      susceptibility and discovered that convulsion effects were significantly enhanced
      when LIS-1 and other pathway components were compromised within the same animals.
      Thus, interactions among gene products with LIS-1 may mediate intrinsic
      thresholds of neuronal synchrony.

PMID- 16996039
TI  - Abnormal laminar position and dendrite development of interneurons in the reeler
      forebrain.
AB  - The majority of cortical and hippocampal interneurons originate in the
      subcortical telencephalon and migrate tangentially into pallial regions before
      settling in various cortical layers. The molecular cues that regulate final
      positioning of specific interneurons in cortical structures have not yet been
      identified. The positioning of radially migrating principal neurons of the cortex
      and hippocampus depends upon Reelin, an extracellular protein expressed near the
      pial surface during embryonic development that is absent in reeler mutant mice.
      To determine whether the layer specification of interneurons, like that of
      principal neurons, requires Reelin, we crossed reeler with transgenic mice that
      contain Green Fluorescent Protein (GFP)-expressing Inhibitory Neurons (GINs).
      These neurons express basal forebrain markers Dlx1/2 in normal and reeler mice.
      In normal mice, GINs express Reelin and are localized to specific layers of the
      cortex and hippocampus. In reeler mutant mice, we show that GINs migrate normally
      into the pallium, but fail to acquire proper layer position. Double labeling
      experiments indicate that the neurochemical profile of these interneurons is not
      generally altered in reeler mice. However, the extension of their cellular
      processes is abnormal. Quantitative analysis of GINs in the cortex revealed that
      they are hypertrophic, bearing longer neuritic branches than normal. Thus, the
      lack of Reelin signaling results in abnormal positioning and altered morphology
      of forebrain interneurons.

PMID- 16996040
TI  - Effect of central administration of QRFP(26) peptide on energy balance and
      characterization of a second QRFP receptor in rat.
AB  - The recently identified neuropeptide QRFP(26) is predominantly expressed in the
      hypothalamus and was suggested to play a role in the regulation of food intake
      following the observation of an acute orexigenic effect after central
      administration in mice. QRFP(26) exerts its effect via GPR103 and a newly
      identified receptor in mouse. The aim of our study was (a) to investigate the
      distribution of QRFP(26) and a newly discovered QRFP receptor mRNA in rat and (b)
      to further characterize the effects of central administration of QRFP(26) on
      energy balance in rats. QRFP(26) mRNA was detected in the retrochiasmatic
      nucleus, periventricular nucleus, arcuate nucleus and restricted areas of the
      lateral nucleus of the hypothalamus. We found an additional receptor with high
      homology for GPR103 in rat. This receptor increases inositol triphosphate
      production in transfected cells in presence of QRFP(26) and its mRNA was
      particularly enriched in ventral and posterior thalamic groups, anterior
      hypothalamus and medulla. When QRFP(26) (10 microg and 50 microg) was
      administered centrally before the start of the light phase both doses increased
      food intake for 2 h after injection without reaching statistical significance.
      QRFP(26) caused no changes in locomotor activity or energy expenditure. In
      summary, central QRFP(26) injection causes slight and transient hyperphagia in
      rats without changing any other energy balance parameters after 24 h. We conclude
      that QRFP(26) has limited impact on the central regulation of energy balance in
      rats and that its essential function remains to be clarified.

PMID- 16996041
TI  - The neural basis of ego- and allocentric reference frames in spatial navigation:
      evidence from spatio-temporal coupled current density reconstruction.
AB  - Different strategies in spatial navigation during passages through computer
      simulated tunnels were investigated by means of EEG source reconstruction. The
      tunnels consisted of straight and curved segments and provided only visual flow,
      but no landmark, information. At the end of each tunnel passage, subjects had to
      indicate their end position relative to the starting point of the tunnel. Even
      though the visual information was identical for all subjects, two different
      strategy groups were identified: one group using an egocentric and the other
      group an allocentric reference frame. The current density reconstruction revealed
      the use of one or the other reference frame to be associated with distinct
      cortical activation patterns during critical stages of the task. For both
      strategy groups, an occipito-temporal network was dominantly active during the
      initial, straight tunnel segment. With turns in the tunnel, however, the
      activation patterns started to diverge, reflecting translational and/or
      rotational changes in the underlying coordinate systems. Computation of an
      egocentric reference frame was associated with prevailing activity within a
      posterior parietal-premotor network, with additional activity in frontal areas.
      In contrast, computation of an allocentric reference frame was associated with
      dominant activity within an occipito-temporal network, confirming right-temporal
      structures to play a crucial role for an allocentric representation of space.

PMID- 16996042
TI  - Long ascending propriospinal projections from lumbosacral to upper cervical
      spinal cord in the rat.
AB  - The retrograde tracer cholera toxin beta-subunit (CTB) was used to trace long
      ascending propriospinal projections from neurons in the lumbosacral spinal cord
      to the upper cervical (C3) gray matter in adult male Sprague-Dawley rats.
      Following large 0.5 microl CTB injections restricted mainly to the upper cervical
      ventral horn (n=5), there were many lumbosacral CTB-positive neurons (14
      17/section) in the intermediate gray and ventral horn (dorsal lamina VIII, medial
      VII extending into X) contralaterally, with fewer at corresponding ipsilateral
      locations. Labeled cells (4-8/section) were also observed in contralateral
      laminae IV-VI and the lateral spinal nucleus, with fewer ipsilaterally. Few
      labeled cells (<2/section) were observed in superficial laminae I-II. Smaller
      (0.15 microl) microinjections of CTB restricted to the upper cervical ventral
      gray matter labeled cells in contralateral laminae VII-VIII (approximately 6
      9/section) with fewer ipsilaterally. There were relatively fewer (<2/section) in
      the intermediate dorsal horn and very few (<1/section) in lamina I. Larger (0.5
      microl) CTB injections encompassing the C3 dorsal and ventral gray matter on one
      side labeled significantly more CTB-positive neurons (>6/section) in
      contralateral lamina I compared to ventral horn injections. These results suggest
      direct projections from ventromedially located neurons of lumbar and sacral
      segments to the contralateral ventral gray matter of upper cervical segments, as
      well as from neurons in the intermediate but not superficial dorsal horn. They
      further suggest that some lumbosacral superficial dorsal horn neurons project to
      the upper cervical dorsal horn. These propriospinal projections may be involved
      in coordinating head and neck movements during locomotion or stimulus-evoked
      motor responses.

PMID- 16996043
TI  - Effects of amantadine and budipine on antidepressant drug-evoked changes in
      extracellular dopamine in the frontal cortex of freely moving rats.
AB  - NMDA receptors play a role in the aetiology of depression with non-competitive
      NMDA receptor antagonists such as amantadine showing synergy with conventional
      antidepressants. To advance a neurochemical rational for these findings, we have
      studied the effects of administration of amantadine and budipine with the
      antidepressants reboxetine (REB), paroxetine (PAROX) and clomipramine (CLOM) on
      extracellular DA in rats using microdialysis. Acutely, amantadine (40 mg/kg) or
      budipine (10 mg/kg) did not significantly alter extracellular DA. REB (10 mg/kg),
      PAROX (10 mg/kg) both increased cortical DA while CLOM (10 mg/kg) produced a
      decrease. When amantadine or budipine was administered 30 min before the
      antidepressants, DA increases were markedly greater than following the
      antidepressants alone. Chronically drug effects were studied at 4, 7, 14 and 21
      days. Amantadine and budipine did not significantly alter extracellular DA at any
      time. The three antidepressants elicited a gradual increase in DA which became
      significant after 7 days and tended to plateau thereafter. When amantadine (20
      mg/kg) or budipine (5 mg/kg) was co-administered with the three antidepressants,
      two differences were seen compared with the antidepressants alone. Firstly, the
      time required for significant increases in cortical DA was reduced with elevated
      levels now being observed by 4 days. Secondly, the increase in extracellular DA
      was greater in these rats throughout the experiment. If increased extracellular
      DA represents a step in the mechanism of action of antidepressants, these data
      suggest that combined treatment with clinically tolerated NMDA antagonists such
      as amantadine could reduce the delay in therapeutic onset of antidepressants and
      possibly enhance their efficacy.

PMID- 16996044
TI  - Goat cerebrovascular reactivity to ADP after ischemia-reperfusion. Role of nitric
      oxide, prostanoids and reactive oxygen species.
AB  - To analyze the cerebrovascular effects of ischemia-reperfusion, cerebrovascular
      reactivity to ADP was studied after inducing 60-min occlusion followed by 60-min
      reperfusion of the left middle cerebral artery (MCA) in anesthetized goats. In 12
      goats, at the end of reperfusion, left MCA resistance was decreased by 19%, and
      reactive hyperemia to 5- and 10-s occlusions as well as the cerebral
      vasodilatation to ADP (0.03-0.3 microg) but not to sodium nitroprusside (0.3-3
      microg) was decreased. In 28 animals, killed at the end of reperfusion, segments
      3-mm long were obtained from the left (ischemic) and right (control) MCA,
      prepared for isometric tension recording, and precontracted with the thromboxane
      A2 analogue U46619. The relaxation to ADP (10(-8) to 10(-5) M) but not to sodium
      nitroprusside (10(-8) to 10(-4) M) was lower in ischemic arteries. L-NAME
      (inhibitor of nitric oxide synthesis, 10(-4) M), charybdotoxin (10(-7) M)+apamin
      (10(-6) M) (blockers of KCa), or catalase (1000 U/ml) reduced the relaxation to
      ADP only in control arteries. Charybdotoxin+apamin further augmented the L-NAME
      induced reduction in the relaxation to ADP in control arteries. The inhibitor of
      cyclooxygenase meclofenamate (10(-5) M) increased the relaxation to ADP only in
      ischemic arteries. The superoxide dismutase mimetic tiron (10(-2) M) increased
      the ADP-induced relaxation only in ischemic arteries. Therefore, it is suggested
      that ischemia-reperfusion produces cerebrovascular endothelial dysfunction, which
      may be associated with decreased nitric oxide bioavailability, decreased release
      of an EDHF, and increased production of vasoconstrictor prostanoids. All these
      alterations may be related in part with an increased production of superoxide
      anion.

PMID- 16996045
TI  - Distribution of pyramidal cells associated with perineuronal nets in the
      neocortex of rat.
AB  - Perineuronal nets are lattice-like accumulations of extracellular matrix
      components around the cell body and perisomatic portion of certain neurons.
      Whereas interneurons associated to this specific neuron-associated sheath have
      been elaborately classified, less effort has been undertaken to describe the
      occurrence of perineuronal nets around pyramidal neurons. Our aim was to give a
      detailed and comparative description of the occurrence of net-associated
      pyramidal cells throughout the rat neocortex as well as to systematically and
      comparatively analyze the relation of main projection types of principal neurons
      to the presence of perineuronal nets. The present study revealed that
      perineuronal nets stained with WFA were associated rather rarely to pyramidal
      cells compared to interneurons in layers II/III and V/VI of rat neocortex.
      However, their frequency was considerably different between various cortical
      areas with a maximum in visual cortex and with a minimum in secondary motor
      cortices. Further analysis revealed that neuron-associated matrix sheaths around
      principal cells were more common in the primary than in the secondary fields of
      corresponding areas and they were more numerous in infra-than in supragranular
      layers in most regions. Subfields of cortical areas also differed regarding the
      occurrence of net-associated principal cells, and the subtlety of cortical
      representation seemed to correlate with the frequency of perineuronal nets around
      pyramidal neurons in the primary somatosensory cortex. It appears that net
      associated pyramidal cells do not have a projection pattern restricted to
      distinct target regions. Rather a functional heterogeneity of the pyramidal cell
      population contributing to specific intra-or subcortical projections is
      suggested.

PMID- 16996046
TI  - Layered expression scanning: multiplex molecular analysis of diverse life science
      platforms.
AB  - With the advent of the genomic era, there is an increasing use of high-throughput
      techniques to generate transcriptome- and proteome-based profiles of biological
      specimens. Each of these methodologies offers a unique window into the inner
      workings of cell and tissue samples. Often, these studies generate large data
      sets and provide investigators with a substantial number of candidate
      dysregulated genes and pathways. Follow-up studies are then undertaken to
      independently validate the original findings and to extend the study to
      additional samples or more quantitative measurements. Although there are several
      methods available for these validation efforts, they are often tedious and
      laborious to perform; thus, additional tools that enable this task are needed.
      One such approach is layered expression scanning (LES), a new technique developed
      via a cooperative research and development agreement (CRADA) between the National
      Cancer Institute and 20/20 GeneSystems, Inc. The technique is based on the
      movement of biomolecules from a two-dimensional life science platform
      (histological tissue section, electrophoresis gel, multi-well plate, etc.)
      through a set of analysis membranes while maintaining the original distribution
      pattern of the molecules. Each membrane measures one analyte and the data are
      then mapped back to the original specimen, permitting each component of the life
      science platform to be studied in detail. LES can be configured in several
      different ways depending on the goals of the study. In this review, we summarize
      the use of the LES technique for a variety of biological applications.

PMID- 16996047
TI  - Effects of hyperbaric oxygen therapy on circulating interleukin-8, nitric oxide,
      and insulin-like growth factors in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The potential benefits of hyperbaric oxygen therapy (HBOT) have been
      reported in diabetic patients with foot ulcers. However, the roles of HBOT on
      wound healing-associated growth factors and inflammatory mediators are not
      completely understood in diabetes mellitus (DM). OBJECTIVES: The aim of this
      study was to investigate the effects of HBOT on circulating cytokines, NO, and
      insulin-like growth factors (IGF) in patients with type 2 DM. DESIGN AND METHODS:
      Serum samples were collected from patients with type 2 DM (n=31) and healthy
      subjects (n=29) before (baseline) and after the first and third exposure.
      RESULTS: Before HBOT, body mass index (BMI) and serum HbA1c were significantly
      greater, whereas serum IGF-I was significantly lower in diabetic patients
      compared to healthy subjects (one-way ANOVA, p<0.05). After adjusting for age,
      gender, and BMI, serum insulin, growth hormone (GH), IGF-II, IGF-binding protein
      (IGFBP)-1, IGFBP-3, leptin, interleukin (IL)-8, and NO were not significantly
      altered by HBOT in diabetic patients and healthy subjects (repeated-measures
      ANOVA). Change in serum insulin (baseline to the third exposure) was a positive
      predictor of changes in leptin and NO in healthy subjects and diabetic patients,
      respectively. CONCLUSIONS: Our results suggest that short-term HBOT may not alter
      the circulating insulin, IGF, leptin, IL-8, and NO levels. In addition, healthy
      subjects and diabetic patients showed differential responses to HBOT in the
      relationships of leptin, insulin, and NO. Further studies are needed to clarify
      the mechanism of HBOT-improved wound healing in diabetic patients with foot
      ulcers.

PMID- 16996048
TI  - Explicit parameterization of sleep EEG transients.
AB  - Adaptive time-frequency approximations, implemented via the matching pursuit
      algorithm, offer description of local signals structures in terms of their time
      occurrence and width, frequency and amplitude. This allows to construct explicit
      filters for finding EEG waveforms, known from the visual analysis, in the
      matching pursuit decomposition of signals. In such a way detectors of relevant
      structures of both transient and oscillatory nature can be constructed in the
      space of physically meaningful parameters. This study presents evaluation of
      changes of power and frequency of sleep spindles and delta waves, related to the
      depth of the sleep, which were previously assessed in a qualitative way. We
      confirm quantitatively the decrease of frequencies of sleep spindles and delta
      waves with the depth of the sleep.

PMID- 16996049
TI  - Interaction of PAR-6 with CDC-42 is required for maintenance but not
      establishment of PAR asymmetry in C. elegans.
AB  - Caenorhabditis elegans embryonic polarity requires the asymmetrically distributed
      proteins PAR-3, PAR-6 and PKC-3. The rho family GTPase CDC-42 regulates the
      activities of these proteins in mammals, flies and worms. To clarify its mode of
      action in C. elegans we disrupted the interaction between PAR-6 and CDC-42 in
      vivo, and also determined the distribution of GFP-tagged CDC-42 in the early
      embryo. Mutant PAR-6 proteins unable to interact with CDC-42 accumulated
      asymmetrically, at a reduced level, but this asymmetry was not maintained during
      the first division. We also determined that constitutively active GFP::CDC-42
      becomes enriched in the anterior during the first cell cycle in a domain that
      overlaps with PAR-6. The asymmetry is dependent on PAR-2, PAR-5 and PAR-6.
      Furthermore, we found that overexpression of constitutively active GFP::CDC-42
      increased the size of the anterior domain. We conclude that the CDC-42
      interaction with PAR-6 is not required for the initial establishment of asymmetry
      but is required for maximal cortical accumulation of PAR-6 and to maintain its
      asymmetry.

PMID- 16996050
TI  - Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and
      development to term.
AB  - The Ca2+ oscillations initiated by the fertilizing sperm (but terminating
      concomitant with pronucleus formation) apparently ensure that the events
      constituting egg activation occur in the correct temporal order; early events
      (e.g., cortical granule exocytosis) require fewer oscillations than later events
      (e.g., recruitment of maternal mRNA). Whether the Ca2+ signaling events impact
      long-term development, in particular development to term, is unknown. Using
      fertilized eggs that have undergone the first few Ca2+ oscillations, we developed
      procedures that result either in inhibiting or stimulating the natural pattern of
      Ca2+ signaling of inseminated eggs. Although the incidence of development to the
      blastocyst stage is unaltered by these procedures, fewer offspring are born
      following embryo transfer, indicating that developmental competence of the
      blastocysts is reduced. Interestingly, embryo transfer experiments reveal that
      when the natural regime of Ca2+ oscillations is precociously interrupted, the
      incidence of implantation is compromised whereas hyper-stimulation of Ca2+
      signaling events compromises post-implantation development. Moreover, although
      there was no major difference in the overall growth rates of the offspring, those
      obtained following hyper-stimulation exhibited a far greater variability in their
      weight. Analysis of global patterns of gene expression by microarray analysis
      revealed that approximately 20% of the transcripts are mis-regulated when too few
      oscillations are experienced by the embryo and EASE analysis indicates that genes
      preferentially involved in RNA processing and polymerase II transcription are
      differentially affected. In addition, a set of genes involved in cell adhesion is
      also mis-expressed and could thus be mechanistically linked to the observed
      reduced implantation. Only about 3% of the transcripts were mis-regulated
      following hyper-stimulation, and EASE analysis indicates that genes
      preferentially involved in metabolism are differentially affected. In toto, these
      results indicate that a range Ca2+ signaling events following fertilization (an
      excess or reduction) has long-term effects on both gene expression and
      development to term.

PMID- 16996051
TI  - Sry and the hesitant beginnings of male development.
AB  - In mammals, Sry (sex-determining region Y gene) is the master regulator of male
      sex determination. The discovery of Sry in 1990 was expected to provide the key
      to unravelling the network of gene regulation underlying testis development.
      Intriguingly, no target gene of SRY protein has yet been discovered, and the
      mechanisms by which it mediates its developmental functions are still elusive.
      What is clear is that instead of the robust gene one might expect as the pillar
      of male sexual development, Sry function hangs by a thin thread, a situation that
      has profound biological, medical and evolutionary implications.

PMID- 16996052
TI  - Computational identification of Ftz/Ftz-F1 downstream target genes.
AB  - Hox genes encode DNA binding transcription factors that regulate the body plans
      of metazoans by regulating the expression of downstream target 'realizator genes'
      that direct morphogenesis and growth. Although some Hox target genes have been
      identified, the code used by Hox proteins to select regulatory targets remains
      elusive. This failure is due, in part, to the overlapping and promiscuous DNA
      binding potential of different Hox proteins. The identification of cofactors that
      modulate Hox DNA binding specificity suggested that target site selection is
      specified by composite binding sites in the genome for a Hox protein plus its
      cofactor. Here we have made use of the fact that the DNA binding specificity of
      the Drosophila Hox protein Fushi Tarazu (Ftz) is modulated by interaction with
      its partner, the orphan nuclear receptor Ftz-F1, to carry out a computational
      screen for genomic targets. At least two of the first 30 potential target genes-
      apontic (apt) and sulfated (Sulf1)--appear to be bona fide targets of Ftz and Ftz
      F1. apt is expressed in stripes within the Ftz domain, but posterior to engrailed
      (en) stripes, suggesting a parasegmental border-independent function of ftz.
      Ftz/Ftz-F1 activate Sulf1 expression in blastoderm embryos via composite binding
      sites. Sulf1 encodes a sulfatase thought to be involved in wingless (Wg)
      signaling. Thus, in addition to regulating en, Ftz and Ftz-F1 coordinately and
      directly regulate different components of segment polarity pathways in parallel.

PMID- 16996053
TI  - Potential toxicological hazard due to endocrine-disrupting chemicals on
      Mediterranean top predators: state of art, gender differences and methodological
      tools.
AB  - Man-made endocrine-disrupting chemicals (EDCs) range across all continents and
      oceans. Some geographic areas are potentially more threatened than others: one of
      these is the Mediterranean Sea. Levels of some xenobiotics are much higher here
      than in other seas and oceans. In this paper we review the final results of a
      project supported by the Italian Ministry of the Environment, in which the
      hypothesis that Mediterranean top predator species (such as large pelagic fish
      and marine mammals) are potentially at risk due to EDCs was investigated. We
      illustrate the need to develop and apply sensitive methodological tools, such as
      biomarkers (Vitellogenin, Zona Radiata proteins and CYP1A activities) for
      evaluation of toxicological risk in large pelagic fish top predators (Swordfish,
      (Xiphias gladius), Bluefin Tuna (Thunnus thynnus thynnus)) and nondestructive
      biomarkers (CYP1A activities and fibroblast cell culture in skin biopsy), for the
      hazard assessment of threatened marine mammals species (Striped Dolphin,
      (Stenella coeruleoalba), Bottlenose Dolphin (Tursiops truncatus), Common Dolphin
      (Delphinus delphis) and Fin Whale (Balaenoptera physalus))exposed to EDCs.
      Differential gender susceptibility to EDCs is also explored both in large pelagic
      fish and in cetaceans. In cetaceans, male specimens showed higher cytochrome P450
      induction (BPMO in skyn biopsies, CYP2B in fibroblasts cell cultures) by
      xenobiotics with respect to females.

PMID- 16996054
TI  - Gender differences in the disposition and toxicity of metals.
AB  - There is increasing evidence that health effects of toxic metals differ in
      prevalence or are manifested differently in men and women. However, the database
      is small. The present work aims at evaluating gender differences in the health
      effects of cadmium, nickel, lead, mercury and arsenic. There is a markedly higher
      prevalence of nickel-induced allergy and hand eczema in women compared to men,
      mainly due to differences in exposure. Cadmium retention is generally higher in
      women than in men, and the severe cadmium-induced Itai-itai disease was mainly a
      woman's disease. Gender differences in susceptibility at lower exposure are
      uncertain, but recent data indicate that cadmium has estrogenic effects and
      affect female offspring. Men generally have higher blood lead levels than women.
      Lead accumulates in bone and increased endogenous lead exposure has been
      demonstrated during periods of increased bone turnover, particularly in women in
      pregnancy and menopause. Lead and mercury, in the form of mercury vapor and
      methylmercury, are easily transferred from the pregnant women to the fetus.
      Recent data indicate that boys are more susceptible to neurotoxic effects of lead
      and methylmercury following exposure early in life, while experimental data
      suggest that females are more susceptible to immunotoxic effects of lead. Certain
      gender differences in the biotransformation of arsenic by methylation have been
      reported, and men seem to be more affected by arsenic-related skin effect than
      women. Experimental studies indicate major gender differences in arsenic-induced
      cancer. Obviously, research on gender-related differences in health effects
      caused by metals needs considerable more focus in the future.

PMID- 16996055
TI  - The chemotherapeutic agent VP16 increases the stability of HB-EGF mRNA by a
      mechanism involving the 3'-UTR.
AB  - VP16 is a chemotherapeutic agent that introduces DNA damage. We demonstrate that
      cellular stress induced by VP16 in the human cervix cancer cell line HeLa
      increases the HB-EGF (heparin binding epidermal growth factor like growth factor)
      mRNA level dose dependently. Maximal induction (10-fold) was observed at 20-40
      microM VP16. Increased HB-EGF peptide levels accompanied the increase in HB-EGF
      mRNA. We investigated the molecular mechanism involved in HB-EGF mRNA induction
      by VP16. Transcription was only slightly increased (60%) as determined by real
      time PCR quantification of transcription from a reporter plasmid containing the
      HB-EGF promoter in front of the luciferase gene. In contrast, HB-EGF mRNA
      stability was increased significantly by VP16 as demonstrated by monitoring HB
      EGF mRNA decay in cells treated with the transcriptional inhibitor actinomycin D.
      The 3'-UTR (3'-untranslated region) of HB-EGF was inserted at the 3'-end of LacZ
      mRNA. VP16 treatment of the cells caused a 5-fold increase in this chimeric mRNA,
      as compared to LacZ without this 3'-UTR. A 186 nucleotide region of HB-EGF
      contains five of the six AUUUA sequences found in the 1454 nucleotide 3'-UTR of
      HB-EGF and we demonstrate that this region caused an approximately 3-fold
      induction of LacZ mRNA when inserted at the 3'-end, as compared to LacZ without
      any insertion at the 3'-end, demonstrating that a significant proportion of the
      effect resides in this region. Induction of HB-EGF by VP16 has important
      implications as HB-EGF has been reported to prevent cell death, which might lower
      the efficacy of chemotherapy. We demonstrate that mRNA stability and in
      particular the HB-EGF 3'-UTR is involved in the HB-EGF mRNA induction.

PMID- 16996056
TI  - Rabbit embryonic stem cell lines derived from fertilized, parthenogenetic or
      somatic cell nuclear transfer embryos.
AB  - Embryonic stem cells were isolated from rabbit blastocysts derived from
      fertilization (conventional rbES cells), parthenogenesis (pES cells) and nuclear
      transfer (ntES cells), and propagated in a serum-free culture system. Rabbit ES
      (rbES) cells proliferated for a prolonged time in an undifferentiated state and
      maintained a normal karyotype. These cells grew in a monolayer with a high
      nuclear/cytoplasm ratio and contained a high level of alkaline phosphate
      activity. In addition, rbES cells expressed the pluripotent marker Oct-4, as well
      as EBAF2, FGF4, TDGF1, but not antigens recognized by antibodies against SSEA-1,
      SSEA-3, SSEA-4, TRA-1-10 and TRA-1-81. All 3 types of ES cells formed embryoid
      bodies and generated teratoma that contained tissue types of all three germ
      layers. rbES cells exhibited a high cloning efficiency, were genetically modified
      readily and were used as nuclear donors to generate a viable rabbit through
      somatic cell nuclear transfer. In combination with genetic engineering, the ES
      cell technology should facilitate the creation of new rabbit lines.

PMID- 16996057
TI  - Retinal and ciliary body pigment epithelium suppress activation of T lymphocytes
      via transforming growth factor beta.
AB  - The ocular microenvironment is immunosuppressive and anti-inflammatory. Pigment
      epithelial (PE) cells isolated from the eye possess a new property of suppressing
      T cell receptor-dependent activation of T cells in vitro. This property depends
      on their capacity to produce cell-surface and soluble inhibitory molecules. The
      iris pigment epithelia (IPE) do so through direct cell-to-cell contact with naive
      T cells, and this suppressive contact is mediated by interactions between B7 and
      membrane-bound TGFbeta that are expressed constitutively on IPE. We have now
      examined whether other ocular PE cells, e.g., retinal pigment epithelia (RPE) and
      ciliary body pigment epithelia (CBPE), have a similar suppressive property by a
      similar process. We have found that RPE and CBPE significantly suppress the
      activation of bystander T cells via soluble inhibitory factors. RPE and CBPE
      secrete different soluble inhibitory factors including TGFbeta1 and TGFbeta2.
      Although IPE cells suppress the activation of bystander T cells by membrane-bound
      TGFbeta, the RPE and CBPE do so by soluble forms of active TGFbeta through
      mechanisms independent of cell contact. These ocular PE cells are capable
      modifying T cell function by enhancing production of regulatory cytokines
      including TGFbeta. We propose that this mechanism of suppression via TGFbeta
      ensures that soluble active TGFbeta is released into the ocular microenvironment
      in order to create the immune privilege of the posterior segment of the eye.

PMID- 16996058
TI  - Smad3 null mice display more rapid wound closure and reduced scar formation after
      a stab wound to the cerebral cortex.
AB  - Following central nervous system injury, adult mammalian neurons do not
      regenerate through regions of scar formation. This regenerative failure is due in
      part to the inhibitory environment of the glial scar at the lesion site.
      Following injury, transforming growth factor beta (TGF-beta) is strongly induced
      and is important to many aspects of the response to injury, including deposition
      of extracellular matrix (ECM) in the glial scar. However, the pathways through
      which TGF-beta signals to mediate these effects are not known. In order to
      examine the contribution of the TGF-beta-induced transcription factor, Smad3, to
      formation of the glial scar after traumatic brain injury, we utilized mice that
      do not express Smad3. We report that Smad3 null mice heal stab wounds to the
      cerebral cortex more rapidly than do wild-type mice. In Smad3 null mice many
      aspects of glial scar formation and the immune response to injury were altered.
      Fewer neutrophils, macrophages/microglia, NG2-positive cells and GFAP-positive
      cells were detected immediately around the lesion in Smad3 null mice. Expression
      of fibronectin and laminin was also reduced. Injury-induced cell proliferation
      was significantly lower in Smad3 null mice around the lesion. There was no
      overall difference between wild-type and Smad3 null mice in immunoreactivity for
      TGF-beta(1) after injury. Thus, our experiments suggest that TGF-beta signaling
      through Smad3 contributes significantly to the immune response and scar formation
      after cortical stab wound injury, delaying recovery through multiple mechanisms.

PMID- 16996059
TI  - Meloidogyne incognita: molecular and biochemical characterisation of a cathepsin
      L cysteine proteinase and the effect on parasitism following RNAi.
AB  - RNA interference has been used to investigate the function of a cathepsin L
      cysteine proteinase Mi-cpl-1, in the plant-parasitic nematode Meloidogyne
      incognita. A reduction in gene transcript was observed and the number of
      nematodes infecting plants was reduced by almost 60% as was the number of
      established females producing eggs at 21 days post-infection. The cysteine
      proteinase activity of M. incognita, reported by the substrate GLUpNA, was
      inhibited by the cysteine proteinase inhibitor Oc-IDeltaD86. A reduction in
      cysteine proteinase activity was also seen following RNAi of Mi-cpl-1 in J2 stage
      nematodes. In situ hybridization analysis in young and mature female nematodes
      has shown that Mi-cpl-1 is expressed in the intestine, which suggests that its
      product is a digestive enzyme. The effects of knocking-out Mi-cpl-1gene function
      were consistent with a reduction in feeding efficiency. Here, we have shown a
      correlation between transcript abundance proteinase activity and parasitic
      success of M. incognita.

PMID- 16996060
TI  - STD and TRNOESY NMR studies for the epitope mapping of the phosphorylation motif
      of the oncogenic protein beta-catenin recognized by a selective monoclonal
      antibody.
AB  - The interaction of the P-beta-Cat(19-44) peptide, a 26 amino acid peptide
      (K(19)AAVSHWQQQSYLDpSGIHpSGATTTAP(44)) that mimics the phosphorylated beta
      Catenin antigen, has been studied with its monoclonal antibody BC-22, by
      transferred nuclear Overhauser effect NMR spectroscopy (TRNOESY) and saturation
      transfer difference NMR (STD NMR) spectroscopy. This antibody is specific to
      diphosphorylated beta-Catenin and does not react with the non-phosphorylated
      protein. Phosphorylation of beta-Catenin at sites Ser33 and Ser37 on the DSGXXS
      motif is required for the interaction of beta-Catenin with the ubiquitin ligase
      SCF(beta-TrCP). beta-TrCP is involved in the ubiquitination and proteasome
      targeting of the oncogenic protein beta-Catenin, the accumulation of which has
      been implicated in various human cancers. The three-dimensional structure of the
      P-beta-Cat(19-44) in the bound conformation was determined by TRNOESY NMR
      experiments; the peptide adopts a compact structure in the presence of mAb with
      formation of turns around Trp25 and Gln26, with a tight bend created by the
      DpS(33)GIHpS(37) motif; the peptide residues (D32-pS37) forming this bend are
      recognized by the antibody as demonstrated by STD NMR experiments. STD NMR
      studies provide evidence for the existence of a conformational epitope containing
      tandem repeats of phosphoserine motifs. The peptide's epitope is predominantly
      located in the large bend and in the N-terminal segment, implicating bidentate
      association. These findings are in excellent agreement with a recently published
      NMR structure required for the interaction of beta-Catenin with the SCF(beta
      TrCP) protein.

PMID- 16996061
TI  - Expression and regulation of Spatzle-processing enzyme in Drosophila.
AB  - The Drosophila melanogaster Toll receptor controls embryonic dorsal-ventral axis
      formation and is crucial for the innate immune response. In both cases, Toll is
      activated by the enzymatically cleaved form of its ligand Spatzle (Spz). During
      axis formation, Spz is cleaved by the maternally provided serine protease Easter
      while the Spatzle-processing enzyme (SPE) activates Spz after infection. We
      confirm the role of SPE in immunity and show that it is a zygotic gene
      specifically expressed in immune tissues implying that the dual activation of Spz
      is achieved by differential spatiotemporal expression of two similar but distinct
      serine proteases.

PMID- 16996063
TI  - Effects of growth hormone and cortisol on the downstream migratory behavior in
      masu salmon, Oncorhynchus masou.
AB  - The effects of ovine growth hormone (oGH) and cortisol on downstream migratory
      behavior in yearling (1(+)) smolts and underyearling (0(+)) parr of masu salmon,
      Oncorhynchus masou, were examined during the downstream migratory period in
      spring using artificial raceways. In May, each of 22 1(+) smolts and 0(+) parr
      were implanted with cholesterol pellets containing 250 microg of oGH and/or 2 mg
      of cortisol. Their downstream migratory behavior was subsequently observed in
      artificial raceways, along with control groups 4-23 days after implantation. In
      1(+) smolts, the frequency of downstream migratory behavior was 23%, 18%, 72%,
      and 82% in the control, oGH, cortisol, and oGH+cortisol-treated groups,
      respectively. The frequency was significantly higher in the cortisol and
      oGH+cortisol-treated groups than in the control and oGH-treated groups. In 0(+)
      parr, the frequency of downstream migratory behavior in the cortisol (82%) and
      cortisol+oGH-treated (90%) groups was significantly higher than in the control
      (18%) and oGH-treated (0%) groups. These results indicate that cortisol is an
      important endocrine factor inducing downstream migratory behavior in both 1(+)
      smolt and 0(+) parr of masu salmon.

PMID- 16996064
TI  - Pre-hospital fluid therapy in the critically injured patient: need for clinical
      studies.

PMID- 16996065
TI  - Malnutrition in acute care patients: a narrative review.
AB  - OBJECTIVES: This narrative review assesses the current prevalence of
      malnutrition, the methods for detection of malnutrition, the factors associated
      with malnutrition, and the effects of malnutrition in the acute care patients.
      DESIGN: A narrative review methodology was employed. DATA SOURCES: CINAHL, Pub
      Med, and MEDLINE electronic databases were searched from 1996 to 2005, for
      English language articles. Search terms of malnutrition, acute care patients,
      nutrition assessment, and nutrition screening were used. REVIEW METHOD: The
      titles and abstracts of 857 articles were examined. Full text of the articles
      were obtained only when abstracts described undernutrition, malnutrition, protein
      energy malnutrition, nutrition assessment, nutrition screening, factors
      contributing to malnutrition, or resultant outcomes of malnutrition in adult
      acute care patients. Additionally, a hand search through reference lists of
      retrieved articles was done. The articles reviewed included empirical reports
      (110), reviews (25), commentaries (4), and reports from professional associations
      (10). RESULTS: Currently, malnutrition ranges from 13-78% among acute care
      patients. Different methods of detecting malnutrition make it difficult to
      determine the prevalence among acute care patients. Additionally, many nutrition
      screening tools used to detect malnutrition have not undergone rigorous testing
      for validity, reliability, sensitivity, and specificity. Numerous personal and
      organizational factors affect the nutritional status of acute care patients.
      Diminished nutritional status contributes to increased use of hospital resources
      and increased hospital costs. CONCLUSION: Malnutrition continues to be a
      significant problem among acute care patients. The Subjective Global Assessment
      tool has the most diagnostic value for acute care patients. Simple measures, like
      documenting height and weight on admission, and assessing patient's nutritional
      intake, weight status, and medications that alter nutritional intake could assist
      in early detection of malnutrition in the acute care patient.

PMID- 16996066
TI  - Redox-sensitive myocardial remodeling and dysfunction in swine diet-induced
      experimental hypercholesterolemia.
AB  - OBJECTIVES: The effects of hypercholesterolemia (HC) on the myocardium and the
      underlying mechanisms are unclear. We tested the hypothesis that diet-induced HC
      induced myocardial fibrosis by regulating the transforming growth factor (TGF)
      beta pathway and apoptosis through increased oxidative stress, and that these
      would be functionally consequential. METHODS: Three groups of pigs (n=6 each)
      were studied after 12 weeks of normal or 2% HC diet, or HC+antioxidant
      supplementation. Cardiac function was evaluated by electron beam computed
      tomography, while fibrogenic mechanisms and apoptosis were evaluated in
      myocardial tissue. RESULTS: HC-induced myocardial fibrosis was accompanied by
      increased ratio of interstitial collagen I/III (1.4+/-0.3 versus 0.5+/-0.1 in
      normal, p<0.05), expression of TGF-beta1 and its downstream smad mediators, as
      well as myocyte apoptosis. These alterations were also associated with a decrease
      in diastolic filling rate compared to normal (134.0+/-10.6 ml/s versus 70.3+/
      14.3 ml/s, p<0.05), but were attenuated in HC animals chronically supplemented
      with antioxidants. CONCLUSIONS: Myocardial injury elicited by experimental HC
      includes redox-sensitive increases in TGF-beta1 expression and apoptosis, which
      are associated with diastolic dysfunction. These observations underscore a role
      of increased oxidative stress in modulating myocardial tissue remodeling and
      dysfunction in vivo in HC.

PMID- 16996067
TI  - Identification and quantification of protein carbonylation using light and heavy
      isotope labeled Girard's P reagent.
AB  - Protein carbonyls are one of the most widely studied markers of oxidative stress.
      Determining increases in the concentration of protein carbonyls known to be
      associated with neurodegenerative diseases, heart disease, cancer and ageing.
      Identification of carbonylation sites in oxidized proteins has been a challenge.
      Even though recent advances in proteomics has facilitate the identification of
      carbonylation sites in oxidized proteins, confident identification remains a
      challenge due to the complicated nature of oxidative damage and the wide range of
      oxidative modifications. Here, we report the development of a multiplexing
      strategy that facilitates confident carbonylated peptide identification through a
      combination of heavy and light isotope coding and a multi-step filtering process.
      This procedure involves (1) labeling aliquots of oxidized proteins with heavy and
      light forms of Girard's reagent P (GPR) and combining them in a 1:1 ratio along
      with (2) LC/MS and MALDI-MS/MS analysis. The filtering process uses LC/MS and
      MALDI-MS/MS data to rule out false positives by rejecting peptide doublets that
      do not appear with the correct concentration ratio, retention time, tag number,
      or resolution. This strategy was used for the identification of heavily oxidized
      transferrin peptides and resulted in identification 13 distinct peptides. The
      competency of the method was validated in a complex mixture using oxidized
      transferrin in a yeast lysate as well as oxidized yeast. Twenty-five percent of
      the peptides identified in a pure oxidized sample of transferrin were
      successfully identified from the complex mixture. Analysis of yeast proteome
      stressed with hydrogen peroxide using this multiplexing strategy resulted in
      identification of 41 carbonylated peptides from 36 distinct proteins.
      Differential isotope coding of model peptides at different concentrations
      followed by mixing at different ratios was used to establish the linear dynamic
      range for quantification of carbonylated peptides using light and heavy forms of
      GPR.

PMID- 16996068
TI  - Optimization of the dopant for the trace determination of polycyclic aromatic
      hydrocarbons by liquid chromatography/dopant-assisted atmospheric-pressure
      photoionization/mass spectrometry.
AB  - The composition of the dopant for the analysis of polycyclic aromatic
      hydrocarbons (PAHs) by liquid chromatography/dopant-assisted atmospheric-pressure
      photoionization/mass spectrometry under reversed-phase conditions was optimized
      to enhance the ionization efficiency for PAHs. The most suitable dopant was a
      toluene/anisole mixture (99.5:0.5, v/v) and it could improve limit of detections
      (LODs) to 0.79-168 ng mL(-1) (signal-to-noise (S/N)=3) for 16 common PAHs. The
      LODs are 3.8-40 times lower than those obtained with toluene alone and are
      comparable to those obtained using gas chromatography/mass spectrometry.

PMID- 16996069
TI  - Evaluation of the separation characteristics of application-specific (volatile
      organic compounds) open-tubular columns for gas chromatography.
AB  - The solvation parameter model is used to characterize the separation
      characteristics of two application-specific open-tubular columns (Rtx-Volatiles
      and Rtx-VGC) and a general purpose column for the separation of volatile organic
      compounds (DB-WAXetr) at five equally spaced temperatures over the range 60-140
      degrees C. System constant differences and retention factor correlation plots are
      then used to determine selectivity differences between the above columns and
      their closest neighbors in a large database of system constants and retention
      factors for forty-four open-tubular columns. The Rtx-Volatiles column is shown to
      have separation characteristics predicted for a poly(dimethyldiphenylsiloxane)
      stationary phase containing about 16% diphenylsiloxane monomer. The Rtx-VGC
      column has separation properties similar to the
      poly(cyanopropylphenyldimethylsiloxane) stationary phase containing 14%
      cyanopropylphenylsiloxane monomer DB-1701 for non-polar and dipolar/polarizable
      compounds but significantly different characteristics for the separation of
      hydrogen-bond acids. For all practical purposes the DB-WAXetr column is shown to
      be selectivity equivalent to poly(ethylene glycol) columns prepared using
      different chemistries for bonding and immobilizing the stationary phase.
      Principal component analysis and cluster analysis are then used to classify the
      system constants for the above columns and a sub-database of eleven open-tubular
      columns (DB-1, HP-5, DB-VRX, Rtx-20, DB-35, Rtx-50, Rtx-65, DB-1301, DB-1701, DB
      200, and DB-624) commonly used for the separation of volatile organic compounds.
      A rationale basis for column selection based on differences in intermolecular
      interactions is presented as an aid to method development for the separation of
      volatile organic compounds.

PMID- 16996070
TI  - Funnelform single-drop microextraction for gas chromatography-electron-capture
      detection.
AB  - A funnelform single-drop microextraction was developed for gas chromatography
      electron-capture detection. A solvent microdrop of 4 microL was formed at the tip
      of a microsyringe needle assembled with a small brass funnel in the
      microextraction. In the funnel, the restricted microdrop was shaken gently by
      circular motion in an aqueous sample solution. Eleven organochlorine and two
      pyrethroid pesticides were used as the model compounds for evaluating the
      microextraction. The parameters affecting the enrichment factor of the
      microextraction were investigated, including the funnel inner angle, solvent
      component, and microdrop volume, etc. With the optimized microextracting
      conditions, the enrichment factors of organochlorines and pyrethroids were 272
      875 and 147-183, respectively. The detection limit was in the range of 1-12 ng/L
      (S/N = 3). The relative standard deviation (RSD) of peak height was less than
      10.2% (n = 8). This proposed technique is simple, convenient, and efficient.

PMID- 16996071
TI  - Quantification of triacylglycerols in butterfat by gas chromatography-electron
      impact mass spectrometry using molar correction factors for [M-RCOO]+ ions.
AB  - A quantitative electron impact GC-MS method using molar correction factors (MCFs)
      for [M-RCOO]+ ions has been developed for determination of molecular species of
      triacylglycerols (TAGs). MCFs were determined by linear calibration for 226 ions
      of 104 TAG species with good reproducibility: on the average, coefficient of
      determination was 0.975 +/- 0.043 and 0.963 +/- 0.115 for saturated and
      unsaturated TAGs, respectively. The MCFs of the sn-1(3) regioisomers of short
      chain TAGs were lower than those of sn-2 isomers indicating ca. 2-3-fold higher
      cleavage of butyroyl and caproyl groups from the primary positions than from the
      secondary position. The method enabled quantification of 139 and 135 individual
      TAG species of butterfat (BF) and interesterified butterfat, respectively,
      including several regioisomers of short-chain TAGs. The most abundant molecular
      species of the even-numbered TAGs in BF were butyroylpalmitoyloleoylglycerol
      (5.05 mol%), butyroyldipalmitoylglycerol (4.75 mol%), and
      palmitoyldioleoylglycerol (3.32 mol%). The method provides an alternative for
      elucidation of nutritional and technological properties of relatively saturated
      TAG mixtures.

PMID- 16996072
TI  - Analysis of neutral and basic pharmaceuticals in sewage treatment plants and in
      recipient rivers using solid phase extraction and liquid chromatography-tandem
      mass spectrometry detection.
AB  - Analytical method was developed which allowed for the detection of four beta
      blockers (acebutolol, atenolol, metoprolol and sotalol), an antiepileptic drug
      (carbamazepine) and three fluoroquinolone antibiotics (ciprofloxacin, ofloxacin
      and norfloxacin) with a single pre-treatment and chromatographic method. The
      method included an isolation and concentration procedure using solid phase
      extraction, a separation step using high performance liquid chromatography and a
      detection procedure applying triple quadrupole mass spectrometry, which was
      working in the multiple reaction monitoring mode. The method was validated for
      ground, surface and sewage influent and effluent waters. Due to ion suppression
      in the electrospray source, the signals monitored for the analytes were less
      intense in sewage waters compared to ground and surface waters. The limits of
      quantification were as low as 1 ng L(-1) in ground water and 3.5 ng L(-1) in
      sewage influent. The method was successfully applied to the determination of the
      target compounds in raw and treated sewages of three treatment plants in Finland
      and in their recipient rivers. The results showed that many of the studied
      compounds pose a moderate to high persistency in sewage treatment as well as in
      the recipient rivers. The analytical protocol presented may be used for more in
      depth studies on the occurrence and fate of these commonly used pharmaceuticals
      in the sewage treatment plants and in the aquatic environment.

PMID- 16996073
TI  - Dechlorination of DDT, DDD and DDE in soil (slurry) phase using
      magnesium/palladium system.
AB  - Mg0/Pd4+ was able to dechlorinate >99% of extractable DDT (initial concentration
      of 10 mg DDT kg(-1) of soil) and >90% of extractable DDT (initial concentration
      of 50 mg DDT kg(-1) of soil) in soil slurry. Mg0/Pd4+ was also found to be
      effective in dechlorinating of 50 mg kg(-1) DDD and DDE, in soil aged for varying
      time periods. GC-MS analyses revealed the formation of 1,1-diphenylethane as an
      end product from DDT, DDE and DDD. To the best of our knowledge this is the first
      report describing the application Mg0/Pd4+ system for remediation of DDT, DDD and
      DDE contaminated soil. We conclude that reductive dechlorination reaction
      catalyzed by Mg0/Pd4+ may be a promising system to remediate soil contaminated
      with DDT and its dechlorinated products such as DDD and DDE.

PMID- 16996074
TI  - Dissolution kinetics of nanodispersed gamma-alumina in aqueous solution at
      different pH: unusual kinetic size effect and formation of a new phase.
AB  - The dissolution of a technical, nanodispersed gamma-alumina in water was studied
      at 25 degrees C in the pH range 3.0 < or = pH < or = 11.0. The obtained kinetic
      dissolution curves showed a distinct pH dependency, whereas only for pH > or =
      4.5 the typical behavior of nanodispersed materials could be observed. X-ray
      powder diffraction analysis and nitrogen adsorption, as well as IR and UV-Raman
      spectroscopy, were used to characterize the solid material collected during and
      at the end of each dissolution experiment. As a result the formation of a new
      aluminum phase-bayerite-could be proven. The analysis of the equilibrium
      concentration enabled us to determine the solubility constant of the
      corresponding phase assuming a pH-dependent species distribution. The rate
      constants of the dissolution process were evaluated using the model of Gibbs free
      energy of cluster formation, which considers the size effect, among other things.
      As a result, we could show that the observed maxima in the concentration profiles
      are due to a size effect of the starting material having a primary particle
      radius of 10.1 nm.

PMID- 16996075
TI  - Kinetics and adsorption behavior of carboxymethyl starch on alpha-alumina in
      aqueous medium.
AB  - The adsorption of carboxymethyl starch (CMS) at the alpha-alumina/aqueous
      solution interface has been investigated through adsorption studies,
      electrokinetics mobility measurements, and FTIR spectroscopy. Zeta potential
      measurements show that the addition of CMS results in a more dramatic increase in
      the absolute zeta potential in the alkaline region, as well as a shift of the
      isoelectric point to lower values, indicating the adsorption of CMS from the
      aqueous solution onto the alumina surface. The positive hydrophilic surface sites
      of alumina are responsible for the adsorption of CMS molecules. The adsorption of
      CMS is possible after charge reversal by the addition of excess CMS. Nearly 30
      min of contact time are found to be sufficient for the adsorption of CMS to reach
      equilibrium. CMS adsorption follows a Langmuir isotherm with adsorption
      capacities of 91.74 mg CMS per gram of alpha-alumina. For the adsorption of CMS,
      pseudo-second-order chemical reaction kinetics provides the best correlation with
      the experimental data. FTIR analysis indicated that CMS forms outer complexes
      with alumina surfaces depending on the shifting of the asymmetric and symmetric
      bands.

PMID- 16996076
TI  - Solvent effect on the aggregate of fluorinated gemini surfactant at silica
      surface.
AB  - The aggregate states of partially fluorinated gemini surfactant
      [(CF3)2CF(CF2)2(CH2)10N(CH3)2]2(CH2)6Br2 (C(F)(5)C10-C6-C10C(F)(5)) on silica
      surface were investigated with atomic force microscopy (AFM) and water contact
      angle (CA) measurement by analyzing the effects of bulk concentration and
      adsorption time on stack state. On surfactant-adsorbed silica surfaces, there was
      a flat surface layer interspersed with some scattering surfactant aggregates. In
      the case of short adsorption times, the aggregates would be hemisphere. In the
      case of long adsorption times, the aggregates would be present in the form of
      bilayers. With the increase of bulk concentration, the adsorbed amount was
      enlarged and the surface layer became more compact. The formation of patchy
      bilayer aggregates indicated the saturation of the surface layer. Furthermore,
      organic solvent effects on the aggregate state of the surfactant on a silica
      surface were studied with four organic solvents, including n-hexane, dehydrated
      ethanol, 1,1,2-trichloro-1,2,2-trifluoroethane, and toluene. With the treatment
      of different organic solvents, the hemisphere aggregates on the surface layer can
      rearrange into spherical bilayer, rodlike monolayer, and branched rodlike
      monolayer aggregates, respectively. The polarity of solvents and affinity of
      organic solvents for surfactant molecules may have a great impact on the stack
      state of the fluorinated gemini surfactant molecules.

PMID- 16996077
TI  - Iron incorporated heterogeneous catalyst from rice husk ash.
AB  - Silica supported iron catalyst was prepared from rice husk ash (RHA) via the sol
      gel technique using an aqueous solution of iron(III) salt in 3.0 M HNO3. The
      sample was dried at 110 degrees C and labeled as RHA-Fe. A sample of RHA-Fe was
      calcined at 700 degrees C for 5 h and labeled as RHA-Fe700. X-ray diffraction
      spectrogram showed that both RHA-Fe and RHA-Fe700 were amorphous. The SEM/EDX
      results showed that the metal was present as agglomerates and the Fe ions were
      not homogeneously distributed in RHA-Fe but RHA-Fe700 was shown to be
      homogeneous. The specific surface areas for RHA-Fe and RHA-Fe700 were determined
      by BET nitrogen adsorption studies and found to be 87.4 and 55.8 m(2) g(-1),
      respectively. Both catalysts showed high activity in the reaction between toluene
      and benzyl chloride. The mono-substituted benzyltoluene was the major product and
      both catalysts yielded more than 92% of the product. The GC showed that both the
      ortho- and para-substituted monoisomers were present in about equal quantities.
      The minor products consisting of 16 di-substituted isomers were also observed in
      the GC-MS spectra of both catalytic products. The catalyst was found to be
      reusable without loss of activity and with no leaching of the metal.

PMID- 16996078
TI  - International validation of pyrogen tests based on cryopreserved human primary
      blood cells.
AB  - Pyrogens as fever-inducing agents can be a major health hazard in parenterally
      applied drugs. For the control of these contaminants, pyrogen testing for batch
      release is required by pharmacopoeias. This has been done either by the in vivo
      rabbit pyrogen test (since 1942) or the limulus amoebocyte lysate test (LAL),
      since 1976. New approaches include cell-based assays employing in vitro culture
      of human immune cells which respond e.g. by cytokine production (IL-1beta; IL-6)
      upon contact with pyrogens. Six variants of these assays have been validated in a
      collaborative international study. The recent successful development of
      cryopreservation methods promises to make standardized immunoreactive primary
      human blood cells available for widespread use. Furthermore, the pretesting of
      donors for infectious agents such as HIV or hepatitis has made it possible to
      develop a safe and standardised reagent for pyrogen testing. Using a total of 13
      drugs, we have validated the pyrogen test based on fresh and cryopreserved human
      whole blood in four laboratories. The test reached >90% sensitivity and
      specificity. In contrast to the LAL, the test was capable of detecting non
      endotoxin pyrogens derived from Gram-positive bacteria or fungi.

PMID- 16996079
TI  - Protein microarray platform for the multiplex analysis of biomarkers in human
      sera.
AB  - Many biomarkers are currently used to monitor patients in clinical studies.
      Technologies which evaluate, validate and monitor biomarkers in a cost effective
      and efficient manner are a necessity. Here we describe the development,
      validation and implementation of a protein microarray platform for the
      quantitative and simultaneous analysis of six proteins: IL-1beta, IL-1ra, IL-6,
      IL-8, MCP-1 and TNFalpha. The platform utilizes a 96-well plate as a solid
      support on which antibodies are immobilized using non-contact piezoelectric
      printing. The reaction is based on a sandwich ELISA and the signal is quantified
      by chemiluminescence with a CCD camera. The robustness and reproducibility of the
      methodology was investigated using the Food and Drug Administration (FDA)
      regulatory guidelines for pharmacokinetic assay validation, in which a spike
      recovery validation test was elaborated and run over 3 days. The method was shown
      to be both quantitative and reproducible, with assay accuracy between 70% and
      130%, and an assay precision of less than 30%. In addition, protein microarray
      performance was compared with the classical ELISA approach. Sera collected from a
      total of 78 individuals were assayed using both approaches. Correlation
      coefficients (R2) between the two technologies were calculated for each of the
      analytes: 0.90 for IL-1beta, 0.60 for IL-1ra, 0.93 for IL-6, 0.96 for IL-8, 0.94
      for MCP-1 and 0.95 for TNFalpha. The results obtained demonstrate the
      applicability of this protein microarray for quantitative and simultaneous
      analysis of IL-1beta, IL-1ra, IL-6, IL-8, MCP-1 and TNFalpha in clinical samples.

PMID- 16996080
TI  - A new bioassay method reveals pathogenicity of Metarhizium anisopliae and
      Beauveria bassiana against early stages of Capnodis tenebrionis (Coleoptera;
      Buprestidae).
AB  - We used a newly developed bioassay method to demonstrate for the first time the
      potential of the entomopathogenic fungi Beauveria bassiana and Metarhizium
      anisopliae to be used for the control of neonate larvae of Capnodis tenebrionis,
      a major threat to stone-fruit orchards in several countries. Four B. bassiana and
      four M. anisopliae isolates were all pathogenic for neonate larvae of C.
      tenebrionis; mortality rates 10 days after inoculation by dipping in a suspension
      with 10(8)conidia/ml varied from 23.5% to 100%. Three of the four M. anisopliae
      isolates caused 100% mortality. In most cases, postmortem hyphal growth and
      sporulation of M. anisopliae or B. bassiana was observed covering the larvae in
      their galleries. The eight isolates were also evaluated for pathogenicity to C.
      tenebrionis eggs at the same dosage. Only two B. bassiana isolates caused
      significant egg hatching reduction of 84.5% and 94.5%. Our results indicate that
      M. anisopliae and B. bassiana may be considered as promising for a new approach
      to prevent larval infestations by C. tenebrionis.

PMID- 16996081
TI  - Lethal and sub-lethal effects of UVB on juvenile Biomphalaria glabrata (Mollusca:
      Pulmonata).
AB  - Although Schistosoma mansoni occurs mainly in the tropics, where intense levels
      of solar radiation are present, the impact of ultraviolet (UV) light on
      schistosome transmission is not known. The purpose of this study was to
      investigate potential effects of UVB (290-320nm) on juvenile Biomphalaria
      glabrata, the snail intermediate host of S. mansoni. Albino and wild-type snails
      were exposed to doses of UVB from UV-fluorescent lamps, and the following were
      measured: survival, photoreactivation (light-mediated DNA repair), effects on
      feeding behavior, and morphological tissue abnormalities. Irradiation with UVB is
      lethal to B. glabrata in a dose-dependent manner. Exposure to white light
      subsequent to UVB irradiation enhances survival, probably by photoreactivation.
      The shell offers some, but not complete, protection. Experiments in which UVB
      transmittance through the shell was blocked with black nail polish suggest that
      injury to both exposed (headfoot) and shell-enclosed (mantle and visceral mass)
      tissues contributes to mortality in lethally irradiated snails. Wild-type
      (pigmented) snails are less susceptible to lethal effects of UVB than albino
      snails, and they may be more capable of photoreactivation. UVB exposure inhibits
      snail feeding behavior, and causes tentacle forks and growths on the headfoot.
      Thus, UVB may influence the life cycle of S. mansoni by both lethal and sub
      lethal damage to the snail intermediate host. However, the ability of snails to
      photoreactivate may mitigate these effects.

PMID- 16996083
TI  - Monitoring the diffusion of single heterotrimeric G proteins in supported cell
      membrane sheets reveals their partitioning into microdomains.
AB  - Supported cell-membrane sheets are promising in vitro systems to investigate the
      properties of membranes with native protein/lipid composition, in particular
      their sub-compartmentalization and the differential localization of proteins
      associated to them. While such studies are usually performed using static
      microscopy techniques, we demonstrate here the potential offered by dynamic
      diffusion measurements. Whereas the overall fluidity of the lipid bilayer was
      preserved, the preparation of the membrane sheets led to the selective
      immobilization of extracellular and transmembrane (TM) glycosylated proteins and
      the anchored proteins/lipids associated with them. Taking advantage of this, we
      investigated the association of the G protein Gq with TM proteins, in particular
      G-protein coupled receptors (GPCRs), by monitoring the changes in diffusion
      occurring after preparation of the supported membranes. Two fluorescently tagged
      Galphaq proteins were constructed, which remained either mostly monomeric in the
      plasma membrane or associated with Gbetagamma in heterotrimers. While both
      constructs diffused similarly in living cells, the preparation of the supported
      membranes led to the selective immobilization of the heterotrimers with minimal
      changes of the diffusion of the monomeric Galphaq. The diverse mobility of
      monomeric and heterotrimeric Galphaq was a result of their different lipid
      anchors as demonstrated by monitoring the diffusion of the corresponding anchors
      alone. We propose that the immobilization of the heterotrimer was caused by its
      partitioning inside membrane microdomains surrounding GPCRs.

PMID- 16996082
TI  - Expression of Kir2.1 and Kir6.2 transgenes under the control of the alpha-MHC
      promoter in the sinoatrial and atrioventricular nodes in transgenic mice.
AB  - Kir2.1 and Kir6.2 are ion channel subunits partly responsible for the background
      inward rectifier and ATP-sensitive K(+) currents (I(K1) and I(KATP)) in the
      heart. Very little is known about how the distribution of ion channel subunits is
      controlled. In this study, we have investigated the expression (at protein and
      mRNA levels) of GFP-tagged Kir2.1 and Kir6.2 transgenes under the control of the
      alpha-MHC promoter in the sinoatrial node (SAN), atrioventricular node (AVN), His
      bundle and working myocardium of transgenic mice. After dissection, serial 10
      microm cryosections were cut. Histological staining was carried out to identify
      tissues, confocal microscopy was carried out to map the distribution of the GFP
      tagged ion channel subunits and in situ hybridization was carried out to map the
      distribution of corresponding mRNAs. We demonstrate heterologous expression of
      the ion channel subunits in the working myocardium, but not necessarily in the
      SAN, AVN or His bundle; the distribution of the subunits does not correspond to
      the expected distribution of alpha-MHC. Both protein and mRNA expression does,
      however, correspond to the expected distributions of native Kir6.2 and Kir2.1 in
      the SAN, AVN, His bundle and working myocardium. The data demonstrate novel
      transcriptional and/or post-transcriptional control of ion channel subunit
      expression and raise important questions about the control of regional expression
      of ion channels.

PMID- 16996084
TI  - New peptide inhibitors of type IB topoisomerases: similarities and differences
      vis-a-vis inhibitors of tyrosine recombinases.
AB  - Topoisomerases relieve topological tension in DNA by breaking and rejoining DNA
      phosphodiester bonds. Type IB topoisomerases such as vaccinia topoisomerase
      (vTopo) and human topoisomerase I are structurally and mechanistically similar to
      the tyrosine recombinase family of enzymes, which includes bacteriophage lambda
      Integrase (Int). Previously, our laboratory identified peptide inhibitors of Int
      from a synthetic peptide combinatorial library. The most potent of these peptides
      also inhibit vTopo. Here, we used the same mixture-based screening procedure to
      identify peptide inhibitors directly against vTopo using a plasmid relaxation
      assay. The two most potent new peptides identified, WYCRCK and KCCRCK, inhibit
      plasmid relaxation, DNA cleavage and Holliday junction (HJ) resolution mediated
      by vTopo. The peptides tested bind double-stranded DNA at high concentrations but
      do not appear to displace the enzyme from its DNA substrate. WYCRCK binds
      specifically to HJ and perturbs the central base-pairing. This peptide also
      accumulates HJ intermediates when it inhibits Int-mediated recombination, whereas
      KCCRCK does not. Interestingly, WYCRCK shares four amino acids with a peptide
      identified against Int, WRWYCR. The octapeptide WRWYCRCK, containing amino acids
      from both hexapeptides, is more potent than either against vTopo. All peptides
      are less potent against the type IA Escherichia coli topoisomerase I or against
      restriction endonucleases. Like the Int-inhibitory peptide WRWYCR, WYCRCK binds
      to HJs, and both inhibit junction resolution by vTopo. Our results suggest that
      the newly identified WYCRCK and peptide WRWYCR interact with a distorted DNA
      intermediate arising during vTopo-mediated catalysis, or interfere with specific
      interactions between vTopo and DNA.

PMID- 16996085
TI  - Hip protectors efficacy and barriers to adoption to prevent fall-related injuries
      in older adults: findings and recommendations from an international workgroup.
AB  - The Journal of Safety Research has partnered with the Injury Center at the
      Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, USA, to
      briefly report on some of the latest findings in the research community. This
      report is the sixth in a series of CDC articles. This conference on Hip Protector
      Use was held at Boston University in June, 2004 under the sponsorship of the
      Injury Center. Hip fractures from falls are a major threat to the health and well
      being of older adults. One approach to hip fracture prevention is the use of hip
      protectors (HPs), soft padding or hard shells embedded within specially designed
      underwear. This conference brought together experts to discuss the efficacy and
      barriers to using HP. Conclusions from the conference included the need for HP
      product specifications and standards of safety and efficacy, testing protocols,
      and efficacy trials. While no single entity was identified to advance these
      initiatives, this effort should be international and should involve collaboration
      between researchers, health care providers and policy-makers, and HP
      manufacturers. Plans are already underway for a second international conference
      in Europe to follow-up these recommendations and develop strategies for
      implementation.

PMID- 16996086
TI  - Should 'Cyrus the Centipede' take a hike? Effects of exposure to a pedestrian
      safety program on children's safety knowledge and self-reported behaviors.
AB  - INTRODUCTION: We report the first evaluation of the popular "Cyrus the Centipede"
      child pedestrian safety program. METHOD: A pre-test/post-test control versus
      experimental condition design was used to assess Cyrus' impact on third graders'
      pedestrian safety knowledge, and self-reported pedestrian behaviors. RESULTS:
      Although some beneficial effects were observed, the program was not reliably
      effective. In particular, the impact of exposure to Cyrus was strongly influenced
      by the individual teacher who delivered it, likely due to the highly unstructured
      nature of the curriculum. SUMMARY: We suggest that: (a) the effectiveness and
      reliability of such programs be demonstrated before they are widely adopted; and
      (b) programs that focus on training children in actual or simulated traffic
      environments may be more effective than those that primarily focus on teaching
      safety facts and rules.

PMID- 16996087
TI  - Textile analysis of heavy weight, mid-weight, and light weight polypropylene mesh
      in a porcine ventral hernia model.
AB  - BACKGROUND: The purpose of this study was to assess the burst strength and
      stiffness of heavy weight (HW), mid-weight (MW), and light weight (LW)
      polypropylene mesh pre-implantation and 5 months post-implantation in a porcine
      ventral hernia model. MATERIALS AND METHODS: HW (95 g/cm2), MW (45 g/cm2), and LW
      (28 g/cm2) polypropylene were tested as dry samples (n = 8/mesh) before
      implantation using a stamp strain machine. Three weeks after creating four hernia
      defects in each mini-pig (n = 18), the polypropylene meshes (8 x 10 cm; 24/mesh
      type) were implanted in the preperitoneal space, ensuring 2 cm overlap
      circumferentially. At 5 months, the mesh was harvested en bloc with the abdominal
      wall. Testing of burst strength and stiffness was repeated on the ex vivo
      specimens. RESULTS: After implantation in the pig for 5 months, the mean burst
      strength and stiffness of HW and MW meshes remains the same. LW mesh with an
      absorbable monofilament in its weave has significant reductions in mean burst
      strength (P = 0.01) and mean stiffness (P < 0.0001). The burst strength for all
      meshes tested was much higher than measured for the abdominal wall fascia alone.
      The degree of shrinkage of the various weight meshes did not differ. CONCLUSION:
      A reduction in mean burst strength and stiffness occurs after 5 months
      implantation of LW polypropylene mesh with an absorbable monofilament. All meshes
      exhibited burst strengths that were much greater than the burst strength of the
      abdominal wall fascia alone. After tissue incorporation, the LW polypropylene
      mesh maintains mean burst strength comparable to MW polypropylene mesh, while
      becoming less stiff than HW mesh. Long-term, this may contribute to more
      physiological abdominal wall compliance after LW polypropylene mesh implantation.

PMID- 16996088
TI  - Comparison of regional cerebral blood flow in two subsets of subcortical ischemic
      vascular dementia: statistical parametric mapping analysis of SPECT.
AB  - BACKGROUND: The brain imaging criteria for subcortical ischemic vascular dementia
      (SIVD), as proposed by Erkinjuntti, incorporated two clinical entities, the
      lacunar state and Binswanger's disease. However it has not been proven whether
      these two subtypes of SIVD have common pathophysiological features. This study
      investigated the changes of regional cerebral blood flow (CBF) in the two subsets
      of SIVD to establish whether these two subtypes could be incorporated into the
      same group for the purpose of conducting clinical trials. METHODS: Twelve SIVD
      patients with predominant white matter lesions, 13 patients with predominant
      lacunar infarctions and 17 controls were evaluated. Single photon emission
      computed tomography (SPECT) was performed to measure the regional CBF, and
      statistical parametric mapping (SPM) was applied to the analysis of the SPECT
      data. RESULTS: The normalized CBF (nCBF) in the bilateral thalami, the anterior
      cingulate gyri, the superior temporal gyri, the caudate heads and the left
      parahippocampal gyrus was significantly decreased in the SIVD patients compared
      to the controls. This pattern of nCBF reduction was same in both the two subtypes
      of SIVD patients. CONCLUSION: Our study suggests that the two subsets of SIVD may
      have a common nCBF abnormality, and Erkinjuntti's criteria offer a solution for
      researchers to identify the more homogeneous group of vascular dementia patients.

PMID- 16996090
TI  - Temporal context discrimination in patients with schizophrenia: associations with
      auditory hallucinations and negative symptoms.
AB  - BACKGROUND: A deficit in remembering the temporal context of events (a type of
      source memory) has been observed in schizophrenia, and suggested to be associated
      with positive symptoms. METHODS: In order to investigate memory for temporal
      context, we administered a list discrimination task to a sample of schizophrenia
      patients and a sample of healthy controls. Participants were required to learn
      two lists of mixed high- and low-frequency words separated by 10 min, then to
      remember whether each word had been presented in the first or in the second list.
      RESULTS: The number of misattributions to the wrong list was significantly higher
      in patients than in healthy controls. However, the group difference was
      eliminated when recall efficiency was covaried. The number of list
      misattributions was higher in patients with auditory hallucinations than in the
      other patients, independently of verbal recall efficiency. By contrast, affective
      flattening and anhedonia were associated with fewer list misattributions of the
      high-frequency words. CONCLUSIONS: It is suggested that auditory hallucinations
      are associated with deficit in processing or remembering the temporal context.
      Conversely, certain negative symptoms are associated with reduced temporal
      context errors. The possible neural mechanisms involved in temporal context
      deficit as well as in these specific clinical symptoms are discussed.

PMID- 16996089
TI  - In vivo demonstration of M3 muscarinic receptor subtype selectivity of
      darifenacin in mice.
AB  - A novel muscarinic receptor antagonist, darifenacin, inhibited specific binding
      of [N-methyl-(3)H]scopolamine ([(3)H]NMS) in the mouse bladder, submaxillary
      gland and heart in a concentration-dependent manner. The inhibitory effect was
      most potent in the submaxillary gland, followed by the bladder and heart. In
      addition, darifenacin inhibited specific [(3)H]NMS binding in the membranes of
      CHO-K1 cell lines expressing muscarinic M(2) and M(3) receptor subtypes, and the
      potency was significantly (22-fold) greater at the M(3) than at the M(2) subtype.
      At 0.5 to 12 h after oral administration of darifenacin, a significant increase
      in K(d) values for specific [(3)H]NMS binding was seen in the bladder,
      submaxillary gland and lung of mice, compared with control values. Also, there
      was a sustained decrease in the B(max) values in the submaxillary gland. These
      data suggest that muscarinic receptor binding of oral darifenacin is rapid in
      onset and of a long duration. On the other hand, oral darifenacin exerted only
      temporary or little binding of muscarinic receptors in the heart and colon.
      Pilocarpine-induced salivary secretion in mice was continuously suppressed by
      oral darifenacin. The time-course of suppression coincided well with that for the
      muscarinic receptor binding in the submaxillary gland. The antagonistic effect of
      darifenacin against the dose-response curves for pilocarpine appeared to be
      insurmountable. In conclusion, the present study has shown that oral darifenacin
      may exert a pronounced and long-lasting binding of muscarinic receptors in
      tissues expressing the M(3) subtype.

PMID- 16996091
TI  - Priming inhibits the right ear advantage in dichotic listening: implications for
      auditory laterality.
AB  - The typical finding in dichotic listening with verbal stimuli is the right ear
      advantage (REA), indicating a left hemisphere processing superiority, thus making
      this an effective tool in studying hemispheric asymmetry. It has been shown that
      the amplitude of the REA can be modulated by instructions to direct attention to
      left or right side. The current study attempted to modulate the REA by changing
      the dichotic listening stimulus situation. In Experiment 1, a consonant vowel
      (CV) syllable prime was presented binaurally briefly before the dichotic stimuli
      (consisting of two CVs). The prime could be the same as either the left or right
      ear dichotic stimulus, or it could be a different stimulus. Participants were
      instructed to report the CV they heard best from the dichotic syllable pair. The
      traditional REA was found when the prime was different from both dichotic
      stimuli. When the prime matched the CV in the left half of the subsequent
      dichotic pair, the REA was increased, while if the prime matched the right half,
      the REA was reduced. In order to see at which perceptual stage the modulation
      takes place, in Experiment 2 the prime was visual, presented on a PC screen. The
      same effect was seen, although the modulation of the REA was weaker. We propose
      that the memory trace of the prime is a source of interference, and causes
      cognitive control of attention to inhibit recognition of stimuli similar to
      recent distractors. Based on previous studies we propose that this inhibition of
      attention is performed by prefrontal cortical areas. Similarities to the
      mechanisms involved in negative priming and implications for auditory laterality
      studies are pointed out.

PMID- 16996092
TI  - Fast recognition of social emotions takes the whole brain: interhemispheric
      cooperation in the absence of cerebral asymmetry.
AB  - Hemispheric asymmetry in emotional perception has been traditionally studied for
      basic emotions and very little is known about laterality for more complex social
      emotions. Here, we used the "redundant target paradigm" to investigate
      interhemispheric asymmetry and cooperation for two social emotions in healthy
      subjects. Facial expressions of flirtatiousness or arrogance were briefly
      presented either unilaterally in the left (LVF) or right visual field (RVF), or
      simultaneously to both visual fields (BVF) while participants responded to the
      target expression (flirtatious or arrogant, counterbalanced between blocks). In
      bilateral conditions the faces could show the same emotion (congruent condition)
      or two different expressions (incongruent condition). No difference between
      unilateral presentations was found, suggesting that the perception of social
      emotions is not hemispherically lateralized. Responses were faster and more
      accurate in bilateral displays with two emotionally congruent but physically
      different faces (i.e., a male and a female expressing the same emotion) than in
      unilateral conditions. This "redundant target effect" was consistent with a
      neural summation model, thereby showing that interhemispheric cooperation may
      occur for social emotions despite major perceptual differences between faces
      posing the same expression.

PMID- 16996094
TI  - Neonatal stress and litter composition alter sucrose intake in both rat dam and
      offspring.
AB  - The early postnatal environment can have long lasting effects on the physiology
      and behavior of both mother and offspring. A great deal of evidence indicates
      that stress during this time period is a risk factor for the future development
      of a multitude of disorders including substance abuse. The maternal separation
      paradigm is used to model such stress in rats. The current study evaluated the
      effects of maternal separation and litter composition on sucrose consumption, a
      non-drug measure of reward, in both male Long-Evans rat offspring and mother. On
      postnatal day 2, rats were cross-fostered, placed in single-sex or mixed-sex
      litters, and subsequently stressed by daily dam-pup separations during the first
      two postnatal weeks. The length of the separation (15 min, 1 h, or 3 h) was
      randomly assigned to each day. A two-bottle choice test was given to maternally
      separated and nonhandled offspring when they were adults, and to dams 2-4 weeks
      after weaning. Intake of a 10% sucrose solution or water was compared for 1 h
      daily across five consecutive days. Rearing condition had a profound effect on
      total fluid intake and sucrose solution intake by both offspring and dam, with
      the separated offspring and dams generally consuming a greater amount of total
      fluid and 10% sucrose solution than their nonhandled counterparts. Litter
      composition also affected consumption, with the offspring from maternally
      separated mixed-sex litters consuming more total fluid and 10% sucrose solution
      than offspring from maternally separated single-sex litters. These results
      indicate that early postnatal and postpartum stress can lead to changes in
      sucrose consumption, a non-drug measure of reward, indicating that such stress
      may alter the underlying brain reward mechanisms.

PMID- 16996093
TI  - Circadian rhythms in electric waveform structure and rate in the electric fish
      Brachyhypopomus pinnicaudatus.
AB  - Weakly electric fish have long been known to express day-night oscillations in
      their discharge rates, and in the amplitude and duration of individual electric
      organ discharges (EODs). Because these oscillations are altered by social
      environment and neuroendocrine interactions, electric fish are excellent
      organisms for exploring the social and neuroendocrine regulation of circadian
      rhythm expression. Previous studies asserting that these oscillations are
      circadian rhythms have been criticized for failing to control temperature and
      randomize feeding regimes, or for running the fish under constant conditions for
      just 2-3 days. Here we show that the day-night oscillations in the EODs of the
      neotropical gymnotiform fish Brachyhypopomus pinnicaudatus free-run for over a
      week under constant photic and thermal conditions, and randomized food
      provisioning. Sex differences were apparent in strength and magnitude of the
      circadian oscillations; male oscillations were stronger and larger. All three
      parameters retain a common oscillation period while differing in the persistence
      of oscillation strength and magnitude, a difference consistent with proposals by
      others that declines of behavioral circadian rhythms may result from breakdowns
      downstream of the central oscillator.

PMID- 16996095
TI  - Malvone A, a phytoalexin found in Malva sylvestris (family Malvaceae).
AB  - The isolation and structure of a phytoalexin, malvone A (2-methyl-3-methoxy-5,6
      dihydroxy-1,4-naphthoquinone) is reported. Malvone A formation is induced in
      Malva sylvestris L. by the plant pathogen Verticillium dahliae. In a turbimetric
      assay for toxicity to V. dahliae, it had an ED50 value of 24 microg/ml. The
      structure of malvone A was determined by MS and NMR spectroscopy, and by X-ray
      crystallographic analysis. The X-ray analysis showed water molecules were located
      in channels that run along the a-axis.

PMID- 16996096
TI  - Americanin, a bioactive dibenzylbutyrolactone lignan, from the seeds of Centaurea
      americana.
AB  - The reversed-phase preparative HPLC analysis of the methanol (MeOH) extract of
      the seeds of Centaurea americana afforded a dibenzylbutyrolactone lignan, 3''-O
      caffeoyl arctiin (named americanin), together with five known lignans, arctiin,
      arctigenin, matairesinol, matairesinoside and lappaol A, and two known
      phytoecdysteroids, 20-hydroxyecdysone and makisterone A. While the structures of
      the known compounds were determined by direct comparison of the spectral data
      with published data, the structure of americanin was elucidated by UV, MS and a
      combination of 1D and 2D NMR spectral analyses. The antioxidant properties and
      toxicity of the extracts and the isolated compounds were determined by the DPPH
      and the brine shrimp lethality assays, respectively.

PMID- 16996097
TI  - Intracrine modulation of gene expression by intracellular generation of active
      glucocorticoids.
AB  - Glucocorticoids (GC) by either up-regulating or down-regulating the expression of
      genes influence cellular processes in every tissue and organ of the body. The
      enzyme 11beta-hydroxysteroid dehydrogenase Type-1 (11beta-HSD-1) confers
      bioactivity upon the inactive GC cortisone (E) and prednisone (P) by converting
      them to cortisol (F) and prednisolone (L), respectively. We sought to investigate
      whether gene expression modulation by GC is under the regulation of an intracrine
      mechanism that determines the intracellular concentration of active GC. Human
      cell lines were transiently and stably co-transfected with an expression
      construct for 11beta-HSD-1 and a GC-responsive reporter gene and incubated with
      active and inactive GC. Whereas in cells that were not transfected with the
      expression construct for 11beta-HSD-1 inactive GC had no transcriptional
      activity, in both transiently and stably transfected cells E and P demonstrated a
      dose-dependent transcriptional activity. This transcriptional potency of both
      inactive GC was effectively abolished by carbenoxolone, an 11beta-HSD-1
      inhibitor, and was directly related to the concentration of transfected 11beta
      HSD-1. We conclude that gene expression modulation by GC is under a decisive
      influence of target cell 11beta-HSD-1 that modulates the intracellular
      concentration of active GC. The intracrine mechanism is an under-appreciated
      aspect of GC activity that could be a potential target for future therapies aimed
      at modulating GC effects at the cellular level.

PMID- 16996098
TI  - Ovarian follicle growth in the catfish Iheringichthys labrosus (Siluriformes:
      Pimelodidae).
AB  - The morphofunctional organisation of the female reproductive system, the oocyte
      growth and the follicular envelope ultrastructure were studied by the first time
      in the catfish Iheringichthys labrosus from Upper Parana River basin,
      Southeastern Brazil, in order to contribute to the knowledge of the reproductive
      behaviour strategies of this species. As in other Neotropical freshwater
      siluriforms, the ovaries are of the cystovarian type, the oocytes develop in an
      asynchronous pattern and mature oocytes are released in clusters in the ovarian
      lumen, being transported through the oviduct to the urogenital papilla. During
      the primary growth, nuclear material is transported to the ooplasm, forming the
      yolk nucleus, where proliferate membranous organelles. The onset of the zona
      radiata formation occurs during the late perionucleolar stage with the deposition
      of the outer layer. At the vitellogenic stage, this envelope reaches 6.35+/
      0.84microm of thickness, being constituted by three distinct layers crossed by
      pore-canals containing oocyte and follicular cells processes. Cytochemical
      analyses evidence neutral glycoproteins in cortical alveoli, yolk globules and
      zona radiata. Follicular cells with squamous shape during the primary growth
      acquire synthetic activity at the secondary growth, reaching 37.82+/-4.72mum in
      height at the mature vitellogenic follicles. These cells accumulate sulphated
      polysaccharides in large electron-lucent vesicles during the vitellogenic stage
      which are possibly secreted to form a mucous coat at the egg surface. These
      evidences suggest that I. labrosus may have adhesive eggs as also detected in
      other Neotropical freshwater Siluriformes.

PMID- 16996099
TI  - A numerical simulation method and analysis of a complete thermoacoustic-Stirling
      engine.
AB  - Thermoacoustic prime movers can generate pressure oscillation without any moving
      parts on self-excited thermoacoustic effect. The details of the numerical
      simulation methodology for thermoacoustic engines are presented in the paper.
      First, a four-port network method is used to build the transcendental equation of
      complex frequency as a criterion to judge if temperature distribution of the
      whole thermoacoustic system is correct for the case with given heating power.
      Then, the numerical simulation of a thermoacoustic-Stirling heat engine is
      carried out. It is proved that the numerical simulation code can run robustly and
      output what one is interested in. Finally, the calculated results are compared
      with the experiments of the thermoacoustic-Stirling heat engine (TASHE). It shows
      that the numerical simulation can agrees with the experimental results with
      acceptable accuracy.

PMID- 16996100
TI  - Experimental study of the influence of different resonators on thermoacoustic
      conversion performance of a thermoacoustic-Stirling heat engine.
AB  - In this paper, an experimental study of the effect of the resonator shape on the
      performance of a traveling-wave thermoacoustic engine is presented. Two different
      resonators were tested in the thermoacoustic-Stirling heat. One resonator is an
      iso-diameter one, and the other is a tapered one. To have a reasonable comparison
      reference, we keep the same traveling-wave loop, the same resonant frequency and
      the same operating pressure. The experiment showed that the resonator shape has
      significant influence on the global performance of the thermoacoustic-Stirling
      heat engine. The tapered resonator gives much better performance than the iso
      diameter resonator. The tapered resonator system achieved a maximum pressure
      ratio of about 1.3, a maximum net acoustical power output of about 450 W and a
      highest thermoacoustic efficiency of about 25%.

PMID- 16996101
TI  - Properties of a herpes simplex virus multiple immediate-early gene-deleted
      recombinant as a vaccine vector.
AB  - Herpes simplex virus (HSV) recombinants induce durable immune responses in rhesus
      macaques and mice and have induced partial protection in rhesus macaques against
      mucosal challenge with virulent simian immunodeficiency virus (SIV). In this
      study, we evaluated the properties of a new generation HSV vaccine vector, an HSV
      1 multiple immediate-early (IE) gene deletion mutant virus, d106, which contains
      deletions in the ICP4, ICP27, ICP22, and ICP47 genes. Because several of the HSV
      IE genes have been implicated in immune evasion, inactivation of the genes
      encoding these proteins was expected to result in enhanced immunogenicity. The
      d106 virus expresses few HSV gene products and shows minimal cytopathic effect in
      cultured cells. When d106 was inoculated into mice, viral DNA accumulated at high
      levels in draining lymph nodes, consistent with an ability to transduce dendritic
      cells and activate their maturation and movement to lymph nodes. A d106
      recombinant expressing Escherichia coli beta-galactosidase induced durable beta
      gal-specific IgG and CD8(+) T cell responses in naive and HSV-immune mice.
      Finally, d106-based recombinants have been constructed that express simian
      immunodeficiency virus (SIV) gag, env, or a rev-tat-nef fusion protein for
      several days in cultured cells. Thus, d106 shows many of the properties desirable
      in a vaccine vector: limited expression of HSV gene products and
      cytopathogenicity, high level expression of transgenes, ability to induce durable
      immune responses, and an ability to transduce dendritic cells and induce their
      maturation and migration to lymph nodes.

PMID- 16996102
TI  - Induction of the CXCL1 (KC) chemokine in mouse astrocytes by infection with the
      murine encephalomyelitis virus of Theiler.
AB  - In the present study, we focused on the production of the chemokine CXCL1, also
      termed KC, by cultured Theiler murine encephalomyelitis virus (TMEV)-infected
      mouse astrocytes. cRNA from mock- and TMEV-infected cells was hybridized to the
      Affymetrix murine genome U74v2 DNA microarray. Hybridization data analysis
      demonstrated upregulation of two sequences coding for IL-8 and related to the GRO
      1 oncogene MGSA. The murine counterpart of the above human genes has been
      reported to be the chemokine CXCL1 or KC, and therefore we studied its
      regulation, confirming its mRNA increase by Northern blots. The presence of CXCL1
      in the supernatants of infected cells was further demonstrated by a specific
      ELISA and its intracellular accumulation by flow cytometry. This secreted CXCL1
      was biologically active in a non species-specific way as it induces
      chemoattraction on human neutrophils and monocyte/macrophages, but not on CD3
      positive lymphocytes. Its induction does not follow the MAP kinase pathway which
      transcripts are decrease in infected cells compared with uninfected astrocytes.
      Two inflammatory cytokines, IL-1alpha and TNF-alpha, which are also induced by
      TMEV in astrocytes, were potent inducers of CXCL1. Nevertheless, both mechanisms
      of induction follow different pathways as antibodies to both cytokines fail to
      inhibit TMEV-induced CXCL1 upregulation. Spinal cords but not brains from TMEV
      infected SJL/J animals contain CXCL1 at the start of clinical signs of the
      disease. As no CXCL1 induction can be detected neither in cultured BALB/c
      astrocytes nor in nervous tissue, we propose an important role for CXCL1 in this
      experimental model of multiple sclerosis as a chemoattractant of destructive
      immune cells.

PMID- 16996103
TI  - Protein-enhanced decarboxylation of the covalent intermediate in benzoylformate
      decarboxylase--Desolvation or acid catalysis?
AB  - Benzoylformate decarboxylase (BFD) enhances the rate of decarboxylation of its
      key intermediate compared to the nonenzymic reaction by a factor of about 10(6).
      It has been proposed that desolvation into a hydrophobic environment will lower
      the reaction barrier in TDP-dependent decarboxylases. The competition of thiamin
      thiazolone diphosphate (TTDP) with the cofactor thiamin diphosphate (TDP)
      provides a dynamic indication of the relative hydrophobicity of the cofactor
      binding site. BFD binds the more polar TDP tightly in the presence of excess
      TTDP. Therefore, desolvation would not be likely to occur during catalysis.
      Unlike TDP enzymes that have electron acceptors as substrates, decarboxylases
      require protonation to produce the precursor to the aldehyde product. A mechanism
      involving an associated acid that traps the carbanion generated upon C-C bond
      breaking will permit diffusional separation of carbon dioxide and generate the
      appropriate precursor to the product aldehyde. This would also account for
      avoidance of a competitive reaction. Hasson's detailed structure of BFD shows a
      highly polar active site with histidines in the vicinity of the substrate.
      Reports of a reduction of k(cat) to near the nonenzymic rate without a large
      effect on Km upon specific replacement of these histidines with alanine fit this
      alternative. In TDP enzymes involving oxidation or condensation, an electrophilic
      substrate or second cofactor will be bound (and no proton will be required). This
      will acquire the electron density of the carbanion itself. In such cases,
      protonated side chains are not functional while hydrophobic environments would
      promote the internal transfer.

PMID- 16996104
TI  - PCDD/PCDF Isomer patterns in waste incinerator flyash and desorbed into the gas
      phase in relation to temperature.
AB  - The influence of temperature on the PCDD and PCDF isomer profiles of a municipal
      waste incinerator flyash and the PCDD/PCDF desorbed from the ash under an inert
      atmosphere was investigated using a bench-scale reactor. Exposure to temperatures
      of 250 degrees C and above resulted in significant changes in the distribution of
      isomers within most dioxin and furan congener groups. The PCDD content tended to
      become more evenly distributed across the range of isomers than was the case for
      the raw flyash, while the PCDF content became concentrated across a relatively
      lower number of isomers. In most cases the desorbed PCDD/PCDF were mainly mono-
      to tri-chlorinated, and hence had a relatively low I-TEQ value. The isomer
      profiles of the desorbed species were also influenced by temperature. There were
      some significant differences between the PCDF isomer profiles of the desorbed
      species and those of the treated flyashes under the same conditions, but no clear
      differences between the PCDD isomer profiles.

PMID- 16996105
TI  - Occurrence of platinum and additional traffic related heavy metals in sediments
      and biota.
AB  - Non-point sources play an important role in metal emissions into surface waters.
      One of the most important non-point sources is automobile traffic. Recent studies
      determining traffic related heavy metals in surface waters have concentrated
      mainly on worst case scenarios by analyzing heavy metal loads in waters and
      sediments close to storm-water overflow inlets. The present study aims at
      identifying traffic related heavy metals in moderately polluted sites, as they
      occur in highly urbanized regions. Therefore, the concentrations of eight traffic
      related metals (Pt, Sb, Mo, Cd, Pb, Cu, Cr and Zn) were determined in sediment
      and crustacean samples from eight different aquatic habitats in the Ruhr
      district, Germany. Traffic related heavy metals could be identified in sediment
      and biota samples as a combination of heavy metals (Pt, Sb, Cd, Pb for sediments
      and Pt and Sb for crustacean samples). Pt concentrations received special
      attention due to the relatively recent occurrence of anthropogenically emitted Pt
      in the environment. At six sampling sites, Pt was detected in sediment and/or
      biota samples. The uptake of Pt compared to other traffic related heavy metals by
      Asellus aquaticus and Gammarus pulex is relatively high and can be compared with
      the uptake rates of essential metals like Zn.

PMID- 16996106
TI  - Partitioning of selected environmental pollutants into organic matter as
      determined by solid-phase microextraction.
AB  - Partitioning/sorption of selected environmental pollutants (PCBs, organochlorine
      insecticides, triazine and amide herbicides) into dissolved humic acids (HA),
      soil and mineral substances was evaluated by measuring their free concentrations
      by solid-phase microextraction (SPME). Compounds were chosen to cover a wide
      range of logK(ow) (2.2-7.6). Two different types of partitioning behaviour for
      dissolved HA were observed. Compounds with logK(ow)>5 partitioned almost
      instantly into HA fraction and the remaining free fraction remained rather
      constant. LogK(HA) and logK(DOC) were calculated and found to be similar for
      commercial HA, HA standard and isolated HA. The behaviour of these compounds in
      soil suspension was similar, but strong sorption on CaCO3 and Florisil was also
      noticed. For compounds with logK(ow)<5, we have not noticed significant changes
      in free concentrations in HA solutions over time. In soil suspension, however,
      some sorption/partitioning was observed over time for some compounds, but it was
      matching the sorption on CaCO3 and Florisil.

PMID- 16996107
TI  - Microbial aspects of the interaction between soil depth and biodegradation of the
      herbicide isoproturon.
AB  - Factors controlling change in biodegradation rate of the pesticide isoproturon
      with soil depth were investigated in a field with sandy-loam soil. Soil was
      sampled at five depths between 0-10 and 70-80 cm. Degradation rate declined
      progressively down the soil profile, with degradation slower, and relative
      differences in degradation rate between soil depths greater, in intact cores
      relative to sieved soil. Neither the maximum rate of degradation, or sorption,
      changed with soil depth, indicating that there was no variation in
      bioavailability. Differences in degradation rate between soil depths were not
      associated with the starting population size of catabolic organisms or the number
      of catabolic organisms proliferating following 100% degradation. Decreasing
      degradation rates with soil depth were associated with an increase in the length
      of the lag phase prior to exponential degradation, suggesting the time required
      for adaptation within communities controlled degradation rates. 16S rRNA PCR
      denaturing gradient gel electrophoresis showed that degradation in sub-soil
      between 40-50 and 70-80 cm depths was associated with proliferation of the same
      strains of Sphingomonas spp.

PMID- 16996108
TI  - On the effect of pH in aromatic photonitration upon nitrate photolysis.
AB  - This paper studies the pH effect on the photonitration of catechol, 1-naphthol,
      naphthalene, and benzene. The pH trend is influenced by the generation of HNO(2)
      and peroxynitrous acid (HOONO) upon nitrate photolysis. HNO(2) can be involved in
      a direct and an indirect nitration process. Direct nitration follows the pH
      distribution of HNO(2) (flexus around 3). Indirect nitration, possibly involving
      nitrosation+oxidation, would be highest around pH3. HOONO can be involved in
      electrophilic nitration, where the initial formation rate of the nitroderivatives
      is proportional to [H(+)], or take part in nitration directly, in which case a
      less important pH effect in photonitration is observed. The relative importance
      of the various nitration pathways for each substrate determines the resulting pH
      effect in photonitration upon nitrate photolysis.

PMID- 16996109
TI  - Disruption of thyroid hormone-mediated Xenopus laevis tadpole tail tip regression
      by hexabromocyclododecane (HBCD) and 2,2',3,3',4,4',5,5',6-nona brominated
      diphenyl ether (BDE206).
AB  - Thyroid hormone regulates amphibian metamorphosis, including the transformation
      of a tadpole into a froglet and regression of the tail. Xenopus laevis tadpole
      tail tips in organ culture (ex vivo) undergo regression when exposed to 3,3',5
      triiodo-l-thyronine (T(3)) and interference by chemicals with this process was
      utilized as a bioassay to detect thyroid hormone disruption. In the present study
      the bioassay was further validated by investigating its response to compound
      induced T(3)-antagonism and - potentiation. Tadpole tail tips were exposed to two
      brominated flame retardants (BFRs) in presence or absence of T(3) at its EC(50)
      (20 nM). T(3)-induced tail tip regression was antagonized by
      2,2',3,3',4,4',5,5',6-nona brominated diphenyl ether (BDE206) and potentiated by
      hexabromocyclododecane (HBCD) in a concentration dependent manner, which was
      consistent with results obtained with a in vitro T(3)-dependent proliferation
      bioassay termed the T-screen. Neither compound induced any effect in the absence
      of T(3). The results indicate that studying possible hormone disrupting effects
      of agonistic, antagonistic or potentiating compounds should include combined
      exposure with the natural hormone at around its EC(50) concentration. The results
      obtained with the tail tip exposures were in accordance with the T-screen
      predictions, and occurred at BFR-concentrations that were only 5-50 times those
      of T(3). The bioassay proved to be suitable not only for detecting T(3)-agonism,
      but also for antagonism and potentiation.

PMID- 16996110
TI  - Adaptive responses of mouse skeletal muscle to contractile activity: The effect
      of age.
AB  - This study has characterised the time course of two major transcriptional
      adaptive responses to exercise (changes in antioxidant defence enzyme activity
      and heat shock protein (HSP) content) in muscles of adult and old male mice
      following isometric contractions and has examined the mechanisms involved in the
      age-related reduction in transcription factor activation. Muscles of B6XSJL mice
      were subjected to isometric contractions and analysed for antioxidant defence
      enzyme activities, heat shock protein content and transcription factor DNA
      binding activity. Data demonstrated a significant increase in superoxide
      dismutase (SOD) and catalase activity and HSP content of muscles of adult mice
      following contractile activity which was associated with increased activation of
      the transcription factors, nuclear factor-kappaB (NF-kappaB), activator protein-1
      (AP-1) and heat shock factor (HSF) following contractions. Significant increases
      in SOD and catalase activity and heat shock cognate (HSC70) content were seen in
      quiescent muscles of old mice. The increase in antioxidant defence enzyme
      activity following contractile activity seen in muscles of adult mice was not
      seen in muscles of old mice and this was associated with a failure to fully
      activate NF-kappaB and AP-1 following contractions. In contrast, although the
      production of HSPs was also reduced in muscles of old mice following contractile
      activity compared with muscles of adult mice following contractions, this was not
      due to a gross reduction in the DNA binding activity of HSF.

PMID- 16996111
TI  - Phase II study of weekly docetaxel in patients with recurrent or metastatic
      endometrial cancer: AGO Uterus-4.
AB  - OBJECTIVE: The aim of this phase II multicenter study was to evaluate the safety,
      toxicity and efficacy of docetaxel administered weekly as first line chemotherapy
      in patients with recurrent or metastatic endometrial cancer. PATIENTS AND
      METHODS: Thirty five patients with recurrent or metastatic endometrial cancer
      without previous chemotherapy were enrolled to receive three 6-week cycles of
      docetaxel 35 mg/m(2)/week with 2-week breaks between the cycles. Therapy response
      was evaluated after every 6-week cycle, and therapy was continued in case of at
      least stable disease. Final therapy response was evaluated after three 6-week
      cycles of docetaxel. RESULTS: Thirty five patients with a median age of 65 years
      (range, 37-80 years) were evaluable for toxicity assessment, one patient
      presented with severe anaphylactic reaction during the second application of
      docetaxel and therapy was discontinued. Subsequently, this patient received
      doxorubicin-cisplatin combination chemotherapy. Another patient was initially
      documented with uterine papillary serous cancer but secondarily confirmed as
      uterine carcinosarcoma. Thus, 33 patients were assessable for response. Overall
      response rate was 21% (3 PR and 4 CR). Three patients showed stable disease.
      Median TTP and OAS were 12 weeks and 43 weeks, respectively. Therapy with weekly
      docetaxel was well tolerated; in particular, no grade 3 or 4 hematological
      toxicities occurred. CONCLUSION: Docetaxel weekly has a favorable toxicity
      profile, is well tolerated and shows encouraging activity in patients with
      advanced endometrial cancer.

PMID- 16996112
TI  - MMP-2 expression associates with CA 125 and clinical course in endometrial
      carcinoma.
AB  - OBJECTIVE: Matrix metalloproteinases have long been associated with aggressive
      behavior of several malignancies, but their role in endometrial cancer has not
      been conclusively established. This study aimed to evaluate the roles of matrix
      metalloproteinase-2 (MMP-2) and -9 (MMP-9) as prognostic factors in endometrial
      carcinoma and their association with CA 125 and other conventional prognostic
      markers. METHODS: The MMP-2 and MMP-9 immunoreactive proteins were evaluated from
      primary tumors of endometrial carcinoma in 266 specimens by using a specific
      monoclonal antibody in immunohistochemical stainings. The median follow-up time
      was 79 months. RESULTS: Expression of the MMP-2 and MMP-9 proteins was found in
      88% and 70% of the primary tumors, respectively. Positive MMP-2 immunostaining
      was associated with a shortened recurrence-free (P=0.04) and cancer-specific
      survival (P=0.05). MMP-2 negativity was linked with a favorable prognosis; only
      one patient developed recurrent disease and died during the follow-up.
      Preoperative serum levels of CA 125 were higher in the patients presenting with
      tumors positive for MMP-2 than in those with negative immunostaining (P=0.03).
      CONCLUSIONS: We suggest that MMP-2 is linked with biologically aggressive nature
      of this cancer type. It seems that MMP-2, but not MMP-9, has some prognostic
      value in endometrial carcinoma. However, the conventional prognostic markers are
      superior to MMP-2 in assessing aggressive behavior and cancer-specific survival
      in endometrial cancer.

PMID- 16996113
TI  - Treatment with paclitaxel plus carboplatin, alone or with irradiation, of
      advanced or recurrent endometrial carcinoma.
AB  - OBJECTIVES: The goal of this study was to evaluate the efficacy and toxicity of
      paclitaxel plus carboplatin in the treatment of primarily advanced or recurrent
      endometrial carcinoma. METHODS: Thirty-seven consecutive patients with advanced
      or recurrent endometrial carcinoma were enrolled in this study. Paclitaxel at a
      dose of 175 mg/m(2) was administered intravenously over 3 h followed by
      carboplatin with area under the curve of 5 to 6 over 1 h at 4-week intervals.
      Five patients were received 50 Gy pelvic irradiation, and 7 were received 50 Gy
      pelvic and 50 Gy paraaortic irradiation, after adjuvant chemotherapy with
      paclitaxel plus carboplatin. Eighteen patients had evaluable lesions. Responses
      were assessed before the use of any irradiation. RESULTS: Eleven patients (61%)
      achieved an objective response, including one complete response (5.6%) and 10
      partial responses (56%). The most common toxicity was hematologic: grade 3 or 4
      leukopenia and neutropenia occurred in 59% and 86% of patients, respectively.
      Three patients (8%) required granulocyte colony-stimulating factor support. One
      patient required a platelet transfusion, and four required blood transfusions.
      There was a single adverse event of anaphylaxis. CONCLUSION: The combination of
      paclitaxel and carboplatin appears to be an effective regimen for the treatment
      of patients with advanced or recurrent endometrial carcinoma with tolerable
      toxicity.

PMID- 16996114
TI  - Cyclooxygenase inhibition and hyperthermia for the potentiation of the cytotoxic
      response in ovarian cancer cells.
AB  - OBJECTIVES: The progression of chemotherapy-resistant cancer confers poor
      prognosis and decreases overall survival in ovarian cancer patients. Adjuvants to
      traditional chemotherapy regimens have become attractive modalities for the
      clinical treatment of refractory or resistant ovarian cancer. We evaluated
      whether the addition of NSAID to hyperthermic chemotherapy would increase
      cytotoxicity in cisplatin- and taxane-treated ovarian cancer cells. METHODS:
      Western blot analysis was utilized to determine COX-2 protein expression levels
      in the 2008, cisplatin-sensitive, and C13*, cisplatin-resistant, cell lines. PGE2
      levels were determined and analyzed as a function of cyclooxygenase activity by
      LC/MS/MS. Cells were treated with cisplatin, docetaxel or paclitaxel in
      combination with either NS-398 or sulindac sulfide at 37 degrees C, 41 degrees C
      or 43 degrees C. Cell viability was determined by a MTS cell proliferation assay.
      RESULTS: Both cell lines expressed COX-2 protein, and NS-398 and sulindac sulfide
      effectively blocked PGE2 production. The addition of a NSAID to cisplatin
      treatment in 2008 and C13* cells offered enhanced cytotoxicity and this effect
      was further enhanced at 41 degrees C. In docetaxel-treated 2008 cells, both NS
      398 and sulindac sulfide offered enhanced cell kill; however, this result was not
      observed in paclitaxel-treated cells. Hyperthermia appeared to play no additional
      role in taxane cytotoxicity enhancement, however no antagonism was detected.
      CONCLUSIONS: Our results suggest that the combination treatment (cisplatin or
      docetaxel in combination with NSAID) cause a dose-dependent enhancement of
      cytotoxicity. Hyperthermia may improve the results of intraperitoneal cisplatin
      therapy, thus warranting further evaluation in clinical studies.

PMID- 16996115
TI  - Precise anatomy of the vesico-uterine ligament for radical hysterectomy.
AB  - OBJECTIVES: To clarify the anatomy of the vesico-uterine ligament (VUL), we
      meticulously separated the VUL under magnification (x2.5) during Okabayashi's
      radical hysterectomy. METHODS: Fifty-nine patients (TNM nomenclature: pTIb: 39,
      pT2a: 5, pT2b: 7, after trans-arterial anticancer-drug infusion treatment for the
      cervical cancer: 8) underwent this meticulous operation. Blood loss was recorded
      at two separate time points: during the separation of the VUL and after removal
      of the uterus. RESULTS: After complete separation of the uterine artery and
      superficial uterine vein from the ureter, we could identify the genuine
      connective tissue of the anterior leaf of the VUL in which we isolate and divide
      a distinct bundle of blood vessels: the cervicovesical vessels that cross over
      the ureter from the bladder to the cervix. The remaining tissues in the anterior
      leaf is only avascular connective tissue. The posterior leaf of the VUL is the
      tissue residing under the ureter connecting the posterior wall of the bladder and
      the lateral cervix/upper lateral vagina. In the connective tissues, we identified
      the middle and inferior vesical veins connecting with the deep uterine vein. The
      division of these veins could separate the urinary bladder with ureters
      completely from the lateral cervix and upper vagina. The mean blood loss during
      the separation of the VUL was 20+/-10 g (N=59) and after radical hysterectomy was
      189+/-91.6 g (N=59). CONCLUSION: A precise network of blood vessels in the VUL is
      identified. The knowledge of this anatomy is important to perform radical
      hysterectomy.

PMID- 16996116
TI  - Tumor hypoxia and expression of c-met in cervical cancer.
AB  - OBJECTIVES: Hypoxia enhances malignant progression by promoting the development
      of metastases and increasing invasiveness. One key regulator that controls
      growth, invasion and metastasis in cancer cells is the growth factor receptor c
      met. The aim of this study, therefore, was to investigate the expression of the c
      met protooncogene in cervical cancers in relation to intratumoral hypoxia levels
      and to clinico-pathological parameters. METHODS: 43 Patients with cervical cancer
      were subjected to intratumoral pO(2) measurement with the Eppendorf electrode and
      biopsies were taken. The tissue was subsequently analyzed by immunohistochemistry
      with an anti-c-met antibody. RESULTS: c-met was expressed in 72% of cervical
      cancers. There was a significantly stronger expression in poorly differentiated
      tumors (r=0.4, p=0.008). Furthermore, c-met expression was significantly
      associated with a spray-like pattern of invasion (p=0.008). However, there was no
      significant relationship between c-met expression and intratumoral hypoxia, pT
      stage, FIGO stage, lymphovascular space involvement, tumor size or overall
      survival. CONCLUSIONS: Although c-met has been shown to be hypoxia-induced in
      vitro, our results suggest that it is not the mediator of deleterious effects of
      hypoxia on clinical outcome in cervical cancer.

PMID- 16996117
TI  - Concurrent radiotherapy with paclitaxel/carboplatin chemotherapy as a definitive
      treatment for squamous cell carcinoma of the uterine cervix.
AB  - OBJECTIVES: To evaluate the toxicity and the efficacy of paclitaxel/carboplatin
      chemoradiotherapy as a definitive treatment for squamous cell cancer of the
      uterine cervix. METHODS: From March 2000 to January 2004, 33 patients with
      squamous cell cancer of the uterine cervix were treated with concurrent
      chemoradiotherapy including 2 cycles of paclitaxel (135 mg/m(2)) and carboplatin
      (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. Seven
      patients received adjuvant chemotherapy with the same chemotherapeutic regimen.
      All patients received external beam radiotherapy with 41.4-51.4 Gy (median 50.4
      Gy) to the whole pelvis. Twenty-eight patients received boost irradiation to the
      cervix by brachytherapy with 25.6-43.3 Gy (median 34.6 Gy) and 5 patients by
      external beam radiotherapy with 10.8-14.4 Gy (median 14.4 Gy). RESULTS: A median
      follow-up period was 27 months (range: 6-53 months). Acute hematological toxicity
      of grade 3 or 4 developed in 20 patients (61%), and acute gastrointestinal
      toxicity of grade 3 developed in 1 patient (3%). Vesicovaginal fistula occurred
      in 2 patients (6%). All patients achieved objective response (CR 70%, PR 30%) in
      2 months after termination of treatment. One patient had a local progression in
      cervix, and 4 patients developed distant metastases. The 3-year estimated disease
      free survival rates for stages I-IIA, IIB, III and IV were 67%, 91%, 88% and 50%,
      respectively. The 3-year estimated survival rates for stages I-IIA, IIB, III and
      IV were 89%, 91%, 88% and 50%, respectively. CONCLUSION: Concurrent
      chemoradiotherapy with paclitaxel and carboplatin is effective to achieve an
      excellent pelvic control.

PMID- 16996118
TI  - A phase I trial of oxaliplatin and topotecan in recurrent ovarian carcinoma.
AB  - OBJECTIVE: Oxaliplatin and topotecan have demonstrated activity as single agents
      against recurrent platinum-sensitive and -resistant ovarian cancer, as well as
      synergy in vitro. This was a dose-finding study of combination therapy with
      weekly topotecan and alternating-week oxaliplatin in patients with recurrent
      epithelial ovarian cancer. METHODS: Eligible patients had a diagnosis of
      recurrent ovarian or primary peritoneal carcinoma, a performance status of 0-2,
      and normal bone marrow, renal, and hepatic function. On days 1 and 15 of a 28-day
      cycle, patients received a fixed dose of oxaliplatin (85 mg/m2) via intravenous
      infusion. On days 1, 8, and 15, patients received an escalating dose of
      intravenous topotecan (2.0-4.0 mg/m2). Five dose levels were planned with a
      minimum cohort of 3 patients at each level. RESULTS: Thirteen patients were
      enrolled and received a total of 50 cycles of chemotherapy. The maximum tolerated
      dose was 85 mg/m2 of oxaliplatin and 3.0 mg/m2 of topotecan, and grade 3
      neutropenia was the dose-limiting toxicity. Four of nine (44%) evaluable patients
      had stable disease or a partial response to the drug combination as assessed by
      cancer antigen-125 levels. CONCLUSIONS: A 28-day schedule of oxaliplatin and
      topotecan is safe and well tolerated. Because of the in vitro synergy observed
      between topoisomerase I inhibitors and platinum derivatives and the tolerability
      reported in the current study, this regimen warrants further investigation.

PMID- 16996119
TI  - Clear cell adenocarcinoma of the vagina in a patient with vaginal endometriosis.
AB  - BACKGROUND: Malignant transformation of endometriosis is an infrequent
      complication of endometriosis. Extragonadal disease is uncommon. CASE: 55-year
      old female presented with postmenopausal bleeding. Physical examination revealed
      a 2-cm polypoid lesion at the posterior vaginal apex, which was found to be a
      moderately differentiated invasive adenocarcinoma. Final pathology at the time of
      definitive surgery demonstrated a clear cell adenocarcinoma of the vagina arising
      in vaginal endometriosis. CONCLUSION: Vaginal endometriosis may lead to the
      development of cancer. Malignancy arising in endometriotic foci is rare, but most
      commonly occurs in the ovary. We report a case of clear cell malignancy arising
      in vaginal endometriosis, adding to only seven cases previously reported. Risk
      factors include unopposed estrogen and obesity, but it may occur in the absence
      of either.

PMID- 16996121
TI  - Both corticotropin-releasing factor and apomorphine reduce prepulse inhibition
      following repeated central infusion of corticotropin-releasing factor.
AB  - The neuropeptide, corticotropin-releasing factor (CRF) has been shown to disrupt
      prepulse inhibition of the acoustic startle response in rodents. Prepulse
      inhibition is deficient in a number of psychiatric disorders. In Experiment 1, we
      examined whether repeated central infusion of CRF alters the reduction in
      prepulse inhibition caused by subsequent CRF infusion or apomorphine injection.
      Repeated intracerebroventricular infusion of CRF (0.3 micro g) did not cause
      tolerance to the effect of CRF on prepulse inhibition. Additionally, repeated CRF
      did not alter the effect of apomorphine (0.25 mg/kg, i.p.) on prepulse
      inhibition. In contrast to other reported results, both CRF and apomorphine
      reduced baseline startle amplitude in the Brown Norway rats, which show low
      prepulse inhibition. In Experiment 2, we showed that a CRF-induced change in
      baseline startle amplitude does not contribute to the CRF-induced decrease in
      percent prepulse inhibition. In Experiment 3, we found that methylphenidate (20.0
      mg/kg, i.p.) increased baseline startle amplitude in Brown Norway rats, yet it
      also decreased percent prepulse inhibition. These results suggest that CRF can be
      administered repeatedly without diminution of its effects on prepulse inhibition,
      and that in Brown Norway rats, compounds that either increase or decrease
      baseline startle amplitude can reduce percent prepulse inhibition independently
      of the effects on baseline startle.

PMID- 16996120
TI  - Olanzapine and fluoxetine administration and coadministration increase rat
      hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone:
      implications for therapeutic actions.
AB  - Olanzapine and fluoxetine elevate the GABAergic neuroactive steroid
      allopregnanolone to physiologically relevant concentrations in rodent cerebral
      cortex. It is unknown if these agents also alter pregnenolone or
      deoxycorticosterone. Since olanzapine and fluoxetine in combination have clinical
      utility and may demonstrate synergistic effects, we investigated neuroactive
      steroid alterations following olanzapine, fluoxetine or coadministration. Male
      rats received IP vehicle, olanzapine, fluoxetine or the combination of both
      agents in higher-dose (0, 10, 20 or 10/20 mg/kg, respectively) and lower-dose (0,
      5, 10 or 5/10 mg/kg, respectively) experiments. Pregnenolone and allopregnanolone
      levels in hippocampus were determined by gas chromatography/mass spectrometry.
      Peripheral deoxycorticosterone and other steroid levels were determined by
      radioimmunoassay. Olanzapine, fluoxetine or the combination increased hippocampal
      pregnenolone and serum deoxycorticosterone in both higher- and lower-dose
      experiments, and elevated hippocampal allopregnanolone in higher-dose conditions.
      No synergistic effects on pregnenolone or allopregnanolone were observed
      following olanzapine and fluoxetine coadministration compared to either compound
      alone. Pregnenolone and its sulfate enhance learning and memory in rodent models,
      and therefore pregnenolone elevations may be relevant to cognitive changes in
      psychotic and affective disorders. Since pregnenolone decreases have been linked
      to depression, it is possible that olanzapine- and fluoxetine-induced
      pregnenolone elevations may contribute to the antidepressant actions of these
      agents.

PMID- 16996122
TI  - Activation of peripheral galanin receptors: differential effects on nociception.
AB  - Numerous reports suggest a significant role of peripheral galanin (GAL) in pain
      transmission; however, due to the lack of selective galanin receptor agonists and
      antagonists, the role of GAL receptors (GalR1-3) in pain transmission remains
      unclear. In this study, a new agonist, M617, that preferentially binds to GalR1,
      a GalR2 agonist (AR-M1896), and a GalR2 antagonist (M871) were tested in the
      periphery to elucidate the role of peripheral GalR1 and GalR2 in nociception.
      Ipsilateral, but not contralateral, hindpaw injection of M617 reduced capsaicin
      (CAP)-induced flinching by approximately 50%, suggesting that GalR1 activation
      produces anti-nociception. This anti-nociceptive effect was blocked by
      intraplantar injection of the non-selective GalR antagonist M35. In contrast
      ipsilateral, but not contralateral, intraplantar injection of GalR2 agonist AR
      M1896 enhanced the CAP-induced nociception (1.7-fold). The GalR2 antagonist M871
      blocked the pro-nociceptive effect of AR-M1896 in a dose-dependent manner. This
      antagonist had no effect on nociceptive behaviors induced by CAP alone. The data
      demonstrate that activation of peripheral GalR1 results in anti-nociception but
      activation of peripheral GalR2 produces pro-nociception. Thus, the use of these
      pharmacological tools may help to elucidate the contribution of GalR subtypes in
      nociceptive processing, identifying potential drug targets for the treatment of
      peripheral pain.

PMID- 16996123
TI  - Effects of the CB1R agonist WIN-55,212-2 and the CB1R antagonists SR-141716 and
      AM-1387: open-field examination in rats.
AB  - This study examined the open-field (O-F) effects in rats of the cannabinoid 1
      receptor (CB1R) agonist WIN-55,212-2 (WIN; 1 to 5.6 mg/kg) and its interaction
      with the CB1R antagonist/inverse agonist SR-141716 (1 to 5.6 mg/kg).
      Additionally, separate studies examined the O-F effects of SR-141716 (1 to 10
      mg/kg) and a newly synthesized CB1R selective antagonist/inverse agonist AM-1387
      (3 and 10 mg/kg) when these ligands were administered alone. Both antagonists are
      characterized in vitro by decreased of GTPgammaS binding and increased cAMP
      accumulation (inverse agonism). WIN dose dependently reduced ambulation
      (horizontal activity) and rearing (vertical activity); SR-141716 completely (WIN
      3 mg/kg) or partially (WIN 5.6 mg/kg) normalized these behaviors. WIN alone
      resulted in circling and in an increased latency to leave the start area of the O
      F, effects blocked by all doses of SR-141716. Both the increased scratching and
      grooming, associated with SR-141716 administration, were attenuated but not
      abolished by WIN. SR-141716 alone tended to reduce ambulation (significant at 10
      mg/kg) and rearing (non-significant), had no effect on latency, and increased
      scratching and grooming (both frequency and duration), at doses of 3 mg/kg and
      up. At the doses examined, AM-1387 had no effect on ambulation, rearing, latency
      but significantly increased scratching (10 mg/kg); there was also a trend for
      increased grooming (both frequency and duration). The O-F profile of WIN suggests
      more similarity with the effects of THC rather than methanandamide (and
      presumably also anandamide). Intrinsic activity (scratching and grooming) by SR
      141716 was re-affirmed and seemed to be associated with administration of AM-1387
      as well. AM-1387 was less potent than SR-141716.

PMID- 16996124
TI  - Acceptability and impact of a partial smoking ban in a psychiatric hospital.
AB  - OBJECTIVE: The acceptability and impact of partial smoking bans in psychiatric
      hospitals are not well documented. We assessed the impact of a partial smoking
      ban in a psychiatric hospital in Switzerland. METHODS: Before the intervention,
      smoking was not allowed in bedrooms and dining rooms, but this ban was not
      enforced. The intervention consisted of banning smoking everywhere, except in
      dedicated smoking rooms. Patients and staff were surveyed before (October 2003,
      49 patients and 57 staff) and 2 months after the smoking ban (April 2004, 54
      patients and 54 staff). Analyses included both patients and staff. RESULTS:
      Compared with baseline, after the intervention twice as many non-smokers reported
      that they were "never" exposed to environmental tobacco smoke (ETS) in bedrooms
      (before=25.0%, after=54.5%, p=0.046), dining rooms (35.5 vs. 65.5%, p=0.037),
      corridors (10.4 vs. 30.9%, p=0.001) and meeting rooms (36.8 vs. 75.0%, p=0.012).
      The smoking ban was loosely enforced; although the ban reduced ETS, substantial
      exposure to ETS remained after it was introduced. Most participants (87%)
      rejected the idea of a total smoking ban. CONCLUSION: The partial smoking ban was
      well accepted and was associated with less exposure to ETS. However, even a
      partial ban proved difficult to enforce in this hospital.

PMID- 16996125
TI  - D-Aspartic acid and nitric oxide as regulators of androgen production in boar
      testis.
AB  - D-Aspartic acid (D-Asp) and nitric oxide (NO) are two biologically active
      molecules playing important functions as neurotransmitters and neuromodulators of
      nerve impulse and as regulators of hormone production by endocrine organs. We
      studied the occurrence of D-Asp and NO as well as their effects on testosterone
      synthesis in the testis of boar. This model was chosen for our investigations
      because it contains more Leydig cells than other mammals. Indirect
      immunofluorescence applied to cryostat sections was used to evaluate the co
      localization of D-Asp and of the enzyme nitric oxide synthase (NOS) in the same
      Leydig cells. D-Asp and NOS often co-existed in the same Leydig cells and were
      found, separately, in many other testicular cytotypes. D-Asp level was dosed by
      an enzymatic method performed on boar testis extracts and was 40+/-3.6 nmol/g of
      fresh tissue. NO measurement was carried out using a biochemical method by NOS
      activity determination and expressed as quantity of nitrites produced: it was
      155.25+/-21.9 nmol/mg of tissue. The effects of the two molecules on steroid
      hormone production were evaluated by incubating testis homogenates, respectively
      with or without D-Asp and/or the NO-donor L-arginine (L-Arg). After incubation,
      the testosterone presence was measured by immunoenzymatic assay (EIA). These in
      vitro experiments showed that the addition of D-Asp to incubated testicular
      homogenates significantly increased testosterone concentration, whereas the
      addition of L-Arg decreased the hormone production. Moreover, the inclusion of L
      Arg to an incubation medium of testicular homogenates with added D-Asp,
      completely inhibited the stimulating effects of this enantiomer. Our results
      suggest an autocrine action of both D-Asp and NO on the steroidogenetic activity
      of the Leydig cell.

PMID- 16996126
TI  - The development of folate-PAMAM dendrimer conjugates for targeted delivery of
      anti-arthritic drugs and their pharmacokinetics and biodistribution in arthritic
      rats.
AB  - The aim of this study was to synthesize folate-dendrimer conjugates as suitable
      vehicle for site specific delivery of anti-arthritic drug (indomethacin) to
      inflammatory regions and to determine its targeting efficiency, biodistribution
      in adjuvant induced arthritic rats. Folic acid was coupled to the surface amino
      groups of G4-PAMAM dendrimer (G4D) via a carbodiimide reaction and loaded with
      indomethacin. The conjugates were characterized by (1)H-NMR and IR spectroscopy.
      The drug content and percent encapsulation efficiency increased with increasing
      folate content for the dendrimer conjugates. The in vitro release rate was
      decreased for the folate conjugates when compared with unconjugated dendrimer
      (DNI). The plasma concentration profile showed a biphasic curve indicating rapid
      distribution followed by slow elimination. The AUC(0-infinity), half-life and
      residence time of indomethacin in inflamed paw was higher for folate-dendrimer
      conjugates. The time-averaged relative drug exposure (r(e)) of the drug in paw
      and overall drug targeting efficiency (T(e)) were higher for folate conjugate
      with 21 folate moieties (4.1 and 2.78, respectively) when compared with DNI (1.91
      and 1.88, respectively). This study demonstrated the superiority of active
      targeting over dendrimer mediated passive targeting and also for the first time,
      folate-mediated targeting of an anti-arthritic drug to the inflammatory tissues.

PMID- 16996127
TI  - Performance of functionally graded implants of polylactides and calcium
      phosphate/calcium carbonate in an ovine model for computer assisted craniectomy
      and cranioplasty.
AB  - Biodegradable functionally graded skull implants on the basis of polylactides and
      calcium phosphate/calcium carbonate were prepared in an individual mould using a
      combination of different processing techniques. A geometrically corresponding
      resection template was designed to enable a craniectomy and cranioplasty with the
      prepared implant in the same operation. After various preliminary experiments
      concerning degradation kinetics, pH evolution during degradation,
      micromorphology, biocompatibility tests in human osteoblast cell cultures and
      surgery of cadaver heads, a new large-animal model was developed for long-term in
      vivo studies. In eight 12-months-old sheep, the surgical templates were used to
      create 4.5 x 5 cm(2) calvarial defects which were then filled with the
      corresponding degradable implants in the same operation. The animals were
      sacrificed after 2, 9, 12 and 18 months, and the implants and the surrounding
      tissues were analysed by computer tomography (CT), macroscopic examination and
      microscopy. The new animal model proved to be reliable and very suitable for
      large individual craniectomies and cranioplasties. The formation of new bone from
      the dural layer of the meninges corresponded well to the degradation of the
      porous inner layer of the implants whereas the skull contour was stabilised by
      the compact outer layer over the follow-up period.

PMID- 16996128
TI  - Long-lasting response of therapy-resistant viral warts to treatment with
      interleukin-2 in a patient with chronic lymphocytic leukemia (CLL) and profound
      immunodeficiency.

PMID- 16996129
TI  - Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple
      myeloma.
AB  - Clinical studies have suggested that bisphosphonates may prolong the survival of
      sub-sets of myeloma patients. Newer nitrogen containing bisphosphonates such as
      zoledronate act, at least in part, by inhibiting farnesyl diphosphate synthase
      and subsequent protein prenylation, furthermore, limited data suggests that
      zoledronate exerts a direct anti-tumour effect against human myeloma cell lines.
      We therefore investigated the anti-myeloma potential of zoledronate in comparison
      to, and in combination with, two other inhibitors of the mevalonate pathway: the
      HMGCoA reductase inhibitor fluvastatin and the farnesyl transferase inhibitor
      SCH66336. We found that fluvastatin was able to inhibit the proliferation of
      myeloma cells more effectively than zoledronate or SCH66336 and that combinations
      of zoledronate and fluvastatin, but not zoledronate and SCH66336 acted
      synergistically. Our data indicated that the anti-proliferative effect of
      mevalonate pathway inhibitors is mediated principally via prevention of
      geranylgeranylation and is the result of both cell cycle arrest and apoptosis
      induction. Microarray and quantitative real-time PCR analyses further
      demonstrated that genes related to apoptosis, cell cycle control, and the
      mevalonate pathway were particularly affected by zoledronate and fluvastatin, and
      that some of these genetic effects were synergistic. We conclude that the
      mechanisms of geranylgeranylation inhibition mediated anti-myeloma effects
      warrant further evaluation and may provide novel targets for future therapeutic
      development.

PMID- 16996130
TI  - Utility of interphase FISH to stratify patients into cytogenetic risk categories
      at diagnosis of AML in an Eastern Cooperative Oncology Group (ECOG) clinical
      trial (E1900).
AB  - We evaluated the efficacy of FISH to detect chromosome anomalies in the
      evaluation of young (<60 years) patients with AML. Patients were enrolled in
      E1900, an ECOG clinical trial for AML. The protocol was designed to collect bone
      marrow or blood for both cytogenetic and FISH studies at study entry (diagnosis).
      FISH for each patient was performed and utilized eight probe sets to detect
      t(8;21), t(9;22), t(11;var), t(15;17), inv(16), +8, -5/5q, and -7/7q. We analyzed
      237 specimens with complete cytogenetic and FISH results. Results for each
      specimen were classified by probe set into one of six categories. The concordance
      rate between cytogenetic and FISH results ranged from 98 to 100% for all probe
      sets and kappa analysis for concordance had a p-value of <0.0001. The high level
      of agreement between cytogenetic and FISH results demonstrate the accuracy of a
      panel of eight FISH probe sets for the detection of significant abnormalities in
      AML. Data from this investigation support the use of FISH as an adjunct method to
      increase the yield of useful cytogenetic results in large cooperative trials and
      demonstrate the potential of FISH as a follow-up study of minimal residual
      disease in ECOG trials.

PMID- 16996132
TI  - Using biological traits to predict species sensitivity to toxic substances.
AB  - Species sensitivity distributions (SSD) assume that sensitivity to toxicants
      within target species is random. While the SSD approach has shown promise, it is
      limited by the fact that data are sparse for most compounds, and that these data
      are largely based on the lethal responses of a small group of testing lab
      species. Here we present an alternative approach, based on the hypothesis that
      organisms' sensitivity to stress is a function of their biology, and can be
      predicted from species traits such as morphology, life history, physiology and
      feeding ecology. Using data from the US EPA's AQUIRE database, we found that four
      species traits explained 71% of the variability in sensitivity to toxicants
      within a group of 12 species exposed to 15 chemicals. Our results indicate that
      this approach has promise, but effort is needed to compile species trait
      information to increase the power, precision and taxonomic representativeness of
      this approach.

PMID- 16996131
TI  - Development of a host-genotype-independent counterselectable marker and a high
      frequency conjugative delivery system and their use in genetic analysis of
      Enterococcus faecalis.
AB  - Enterococcus faecalis is a gram-positive commensal bacterium of the
      gastrointestinal tract. E. faecalis is also an opportunistic pathogen that
      frequently exhibits resistance to available antibiotics. Despite the clinical
      significance of the enterococci, genetic analysis has been restricted by
      limitations inherent in the available genetic tools. To facilitate genetic
      manipulation of E. faecalis, we developed a conjugative delivery system for high
      frequency introduction of cloned DNA into target strains of E. faecalis and a
      host-genotype-independent counterselectable marker for use in markerless genetic
      exchange. We used these tools to construct a collection of E. faecalis mutant
      strains carrying defined mutations in several genes, including ccfA, eep, gelE,
      sprE, and an alternative sigma factor (sigH). Furthermore, we combined these
      mutations in various permutations to create double mutants, triple mutants, and a
      quadruple mutant of E. faecalis that enabled tests of epistasis to be conducted
      on the pheromone biosynthesis pathway. Analysis of cCF10 pheromone production by
      the mutants revealed that both the ccfA2 and delta eep10 mutations are epistatic
      to mutations in gelE/sprE. To our knowledge, this represents the first example of
      epistasis analysis applied to a chromosomally encoded biosynthetic pathway in
      enterococci. Thus, the advanced tools for genetic manipulation of E. faecalis
      reported here enable efficient and sophisticated genetic analysis of these
      important pathogens.

PMID- 16996133
TI  - Liver lesions produced by aflatoxins in Rana catesbeiana (bullfrog).
AB  - This study describes alterations induced in Rana catesbeiana (bullfrog) liver
      after extended dietary exposure to aflatoxins (AFs). Bullfrogs of both sexes were
      fed for 120 days a commercial chow blended with a rice bran-based mixture of AFs
      containing 667.0, 11.65, 141.74, and 3.53 mg/kg of AFs B1, B2, G1, and G2,
      respectively. Animals were sacrificed on study days 45, 90, and 120. Severe and
      progressive liver lesions with structural collapse, increased hepatocyte and
      biliary duct cell proliferation, appearance of basophilic hepatocytes, and
      diffuse scarring, were observed at all time points. There were no quantitative
      alterations in the liver melanomacrophage centers of the AFs-exposed animals.
      Increased amounts of lipid hydroperoxides, indicative of ongoing oxidative
      stress, were more evident in the Addutor magnum muscle than in the AFs-damaged
      livers. No tumors were found in the R. catesbeiana livers after 120 days of
      exposure to relatively high doses of AFs.

PMID- 16996134
TI  - Phragmites australis and Quercus robur leaf extracts affect antioxidative system
      and photosynthesis of Ceratophyllum demersum.
AB  - During senescence, leaves are deposited on aquatic bodies and decay under water
      releasing chemical substances that might exert physiological stress to aquatic
      organisms. Leaf litter alone contributes 30% of the total dissolved organic
      carbon (DOC) in streams. We investigated the impact of leaves extract from
      Phragmites australis and Quercus robur on the antioxidative system and
      photosynthetic rate of the aquatic macrophyte Ceratophyllum demersum exposed for
      24h. Rate of photosynthetic oxygen release and antioxidant enzyme activity
      (glutathione S-transferases, glutathione reductases and peroxidases) as well as
      lipid peroxidation in C. demersum were measured. Significant (P<0.01) elevations
      of antioxidative enzyme activity in C. demersum which tends to plateau at high
      DOC concentrations were observed. There was no detectable effect on lipid
      peroxidation. A significant dose-dependent reduction in photosynthetic oxygen
      production was measured.

PMID- 16996135
TI  - Synthesis, characterisation and insulin-mimetic activity of oxovanadium(IV)
      complexes with amidrazone derivatives.
AB  - The complexation of VO(2+) ion by ten acetamidrazone and 2-phenylacetamidrazone
      derivatives (L) was studied. Sixteen novel VO(2+) complexes were synthesised and
      characterised through the combined application of analytical and spectroscopic
      (EPR (electron paramagnetic resonance), FT-IR and diffuse reflectance electronic
      absorption) techniques. Eight are 1:2 species of composition [VOL(2)]SO(4) x
      xH(2)O and eight are 1:1 species with formula [VOL(SO(4))](n) x xH(2)O. The
      experimental data suggest a bidentate coordination mode for L with the donor set
      formed by the imine nitrogen and the carbonyl oxygen. EPR spectra indicate a
      square-pyramidal geometry for the 1:1 complexes and a penta-coordinated geometry
      intermediate between the square-pyramid and the trigonal-bipyramid for the 1:2
      species. The hyperfine coupling constant along z axis, A(z), of the 1:2 complexes
      exhibits a marked reduction with respect to the predicted value (approximately
      148x10(-4)cm(-1) vs. approximately 170x10(-4)cm(-1)). IR spectroscopic evidence
      supports the presence of sulphate as a counter-ion in the 1:2, and as a bridging
      bidentate ligand in the 1:1 complexes. Insulin-mimetic tests on modified
      fibroblasts, based on a modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      2H-tetrazoliumbromide) assay, performed on three of the bis-chelated and eight of
      the mono-chelated derivatives, indicate that they are biologically active. The
      similar hydro/lipophilicity and the lack of ligand substituents recognizable by
      cell membrane receptors prevent substantial differentiation in the insulin
      mimetic action.

PMID- 16996136
TI  - Nociceptive withdrawal reflexes evoked by uniform-temperature laser heat
      stimulation of large skin areas in humans.
AB  - Nociceptive withdrawal reflexes (NWR) were evoked by brief (200 ms) painful CO(2)
      laser stimulation at five intensities (1.2, 1.4, 1.6, 1.8, and 2.0 x pain
      threshold) applied to nine sites (2 cm(2)) separated by 1.7 cm on the dorsal side
      of the foot and anterior part of the lower leg of 14 healthy volunteers. The
      purpose of the study was to investigate the characteristics of NWRs evoked by a
      natural stimulation modality. The reflexes were measured as the electromyographic
      response from the iliopsoas (ILI), quadriceps vastus lateralis (QVL), biceps
      femoris (BF), tibialis anterior (TA), and soleus (SOL) muscles. Stimulus-response
      relationships between heat intensity and the reflex magnitude and correlation
      between perceived pain intensity and reflex magnitude were observed in the ILI,
      QVL, BF, and TA but not the SOL. No significant differences in reflex magnitude
      were found between the stimulation sites. NWRs were evoked more often in flexor
      muscles than extensor muscles, indicating a non-site-specific reflex
      organization. The paper presents a new method to evoke NWRs by uniform
      temperature laser heat stimulation of large skin areas in humans. These heat
      evoked reflexes had a stimulus-response relationship.

PMID- 16996137
TI  - Dimensions underlying outcome criteria in bipolar I disorder.
AB  - OBJECTIVE: Various subjective and objective criteria are used to assess outcome
      in bipolar disorder. In this study, we explored to what extent they reflect
      distinct categories and whether underlying dimensions can be identified. PATIENTS
      AND METHODS: One-hundred and twenty-one subjects with at least three episodes of
      bipolar I disorder (DSM-IV) were assessed on average 4.8 years after
      hospitalization. We assessed 14 variables reflecting different outcome criteria
      including subjective quality of life (SQOL), self-rated and observer-rated
      psychopathology, and functioning and disability. A principal component analysis
      was computed across all outcome variables. Identified dimensions were correlated
      with sociodemographic characteristics, illness history, premorbid adjustment and
      personality traits. RESULTS: Three outcome dimensions were identified, i.e. a
      'general subjective', a 'functioning/disability' and a 'manic/psychotic symptoms'
      dimension. Together they explain 69% of the total variance. The 'general
      subjective' dimension consists of SQOL scales and self-rated depressive symptoms.
      It is associated with comorbid anxiety disorders and personality disorders, high
      neuroticism and not having been in hospital in the last year. The
      'functioning/disability' dimension comprises of criteria reflecting negative
      symptoms, disability and low functioning. It is associated with more prior
      illness episodes and low premorbid adjustment. The 'manic/psychotic symptoms'
      dimension consists of observer-rated manic and positive psychotic symptoms. It is
      correlated with not currently taking a specific medication. LIMITATIONS: Cross
      sectional design with a limited sample size. CONCLUSION: The findings indicate
      that outcome criteria in bipolar I disorder can be grouped into three distinct
      dimensions reflecting (1) subjective appraisals, (2) functioning/disability and
      (3) manic/psychotic symptoms. While measurement of psychotic/manic symptoms has
      become a matter of course, until now few studies have assessed disability or
      subjective appraisal in bipolar illness. Therefore important aspects of bipolar
      illness might be overseen. For a better understanding, we suggest that
      longitudinal studies of bipolar I disorders should consider all three dimensions
      of outcome and measure them separately.

PMID- 16996138
TI  - The assessment of anhedonia in clinical and non-clinical populations: further
      validation of the Snaith-Hamilton Pleasure Scale (SHAPS).
AB  - BACKGROUND: Anhedonia, the inability to experience pleasure, is a major
      endophenotype of depression. In addition to this, it is an important clinical
      feature of schizophrenia and substance abuse disorders. Valid instruments to
      measure anhedonia are sparse. METHODS: In the present study, a short, 14-item
      instrument, the Snaith-Hamilton Pleasure Scale (SHAPS) to measure anhedonia in
      normal and clinical samples was further validated. Various aspects of the
      reliability and validity of the SHAPS that have not been addressed before, were
      examined in three separate studies. First, we assessed the internal consistency,
      convergent and discriminative validity of the SHAPS in a non-clinical sample.
      Second, the test-retest reliability of the SHAPS was investigated in another
      sample. In the third study, the internal consistency, convergent and
      discriminative validity of the SHAPS was tested by administering the scale in
      three clinical samples of psychiatric inpatients. RESULTS: The SHAPS was found to
      be highly reliable in terms of internal consistency and test-retest stability.
      Further, the SHAPS correlated in a theoretically meaningful way with other
      measures of affect and personality. Patients with a depression, psychosis or
      substance dependence scored significantly higher on the SHAPS than non-patient
      controls. Patients with a depression displayed the highest SHAPS-score.
      LIMITATIONS: The absence of structured assessment data to validate the clinical
      diagnoses. CONCLUSIONS: The current study shows that the SHAPS is a reliable and
      valid questionnaire to assess hedonic tone in patient and non-patient
      populations. Because it is a brief scale it seems to be a very useful instrument
      for measuring anhedonia in clinical and research settings.

PMID- 16996139
TI  - Is there evidence of an association between postnatal distress and premenstrual
      symptoms?
AB  - BACKGROUND: There is a widely held assumption in the literature that a well
      established link exists between postnatal depressive and premenstrual symptoms.
      However, on examination of existing research, certain methodological limitations
      were identified including inadequate methods of assessment and a heavy reliance
      upon the retrospective assessment of either postnatal or premenstrual symptoms,
      giving rise to concern regarding the validity of any conclusions. METHODS: A
      community sample of 63 women completed a daily menstrual symptom diary for two
      consecutive months. Women's Edinburgh Postnatal Depression Scale score, recorded
      1-3 years previously, was provided by their Health Visitor. RESULTS: Only one
      participant showed evidence of both postnatal and premenstrual distress when
      using an EPDS cut-off of >12 and defined criteria for premenstrual symptom
      assessment. When scores were treated as a continuum, there was no association
      between postnatal distress and psychological premenstrual symptoms and only a
      trend towards significance between postnatal distress and physical premenstrual
      symptoms. LIMITATIONS: Due to the recruitment method, there is some uncertainty
      regarding the overall response rate. Although this was not a large sample, it
      compares favourably with many other studies where daily data are collected. The
      particular focus was examining whether postnatal depressive symptoms predict
      premenstrual distress (not vice versa). CONCLUSIONS: This study found little
      evidence to support the widely held assumption of a clear relationship between
      postnatal distress and premenstrual symptoms.

PMID- 16996140
TI  - Prediction of treatment response in major depression: integration of concepts.
AB  - BACKGROUND: Two promising approaches have been introduced for the prediction of
      treatment response in major depression: one concept is based on the activity in
      the rostral anterior cingulate cortex (rACC). Subjects with higher metabolic
      rates respond better to sleep deprivation or antidepressive medication. Another
      approach is the investigation of the loudness dependence of the auditory evoked
      potential (LDAEP). Here, a high LDAEP is supposed to reflect low central
      serotonergic activity. We present the first study comparing both approaches in
      the same group of patients. METHODS: Patients with major depression (n=20) were
      investigated using both resting EEG and LDAEP before treatment with either
      citalopram or reboxetine. RESULTS: We found significant differences between
      responders and non-responders in the rACC in the theta-frequency range (6.5-8 Hz,
      p<0.05). In the subgroup of patients, treated with citalopram we found higher
      LDAEP-values in responders versus non-responders (p<0.05) and a significant
      correlation between pre-treatment-LDAEP and improvement in the Hamilton score
      after treatment (r=0.71, p<0.05). CONCLUSIONS: In combining both methods a
      prediction whether a patient with major depression might be at risk for non
      response to a standard therapy as well as a suggestion for a pharmacological
      approach of choice seems to be possible.

PMID- 16996141
TI  - Analysis of chicken cytokine and chemokine gene expression following Eimeria
      acervulina and Eimeria tenella infections.
AB  - The expression levels of mRNA encoding a panel of 28 chicken cytokines and
      chemokines were quantified in intestinal lymphocytes following Eimeria acervulina
      and Eimeria tenella primary and secondary infections. Compared with uninfected
      controls, transcripts of the pro-inflammatory cytokines IFN-alpha, IL-1beta, IL
      6, and IL-17 were increased up to 2020-fold following primary infection. By
      contrast, following secondary infection by either microorganism, pro-inflammatory
      mRNAs levels were relatively unchanged (< or = 20-fold). Transcripts encoding the
      Th1 and Th1 regulatory cytokines IFN-gamma, IL-2, IL-10, IL-12, IL-15, IL-16, and
      IL-18 were uniformly increased 14-2471-fold after E. acervulina primary
      infection, but either unchanged (IL-15, IL-16, IL-18), increased (IFN-gamma, IL
      10, IL-12), or decreased (IL-2) following E. tenella primary infection. Following
      secondary infections, Th1 cytokine mRNA levels were relatively unchanged, with
      the exception of IL-12 which was increased 1.5 x 10(5)-fold after E. acervulina
      and decreased 5.1 x 10(4)-fold after E. tenella infection. Transcripts for the
      Th2 or Th2 regulatory cytokines IL-3 and GM-CSF were increased up to 327-fold
      following primary or secondary infection with both parasites, while IL-4 and IL
      13 mRNAs were decreased 25- to 2 x 10(5)-fold after primary or secondary
      infection. The dynamics of chicken chemokine expression revealed modest changes
      (<100-fold) following primary or secondary infection except for lymphotactin.
      When lymphocyte subpopulations were similarly analyzed, IFN-gamma, IL-2, IL-3, IL
      15, and MIF were most highly increased in TCR2(+) cells following E. acervulina
      infection, while TCR1(+) cells only expressed high levels of IL-16 following E.
      tenella infection. In contrast, CD4(+) cells only expressed highest levels of IL
      10 after E. acervulina infection, whereas these cells produced abundant
      transcripts for IFN-gamma, IL-3, IL-15, and MIF after E. tenella infection. We
      conclude that coccidiosis induces a diverse and robust primary cytokine/chemokine
      response, but a more subdued secondary response.

PMID- 16996142
TI  - The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in
      experimental autoimmune encephalomyelitis.
AB  - We studied the role of fasudil, a selective Rho-kinase inhibitor, in experimental
      autoimmune encephalomyelitis (EAE). Both parenteral and oral administration of
      fasudil prevented the development of EAE induced by proteolipid protein (PLP)
      p139-151 in SJL/J mice. Specific proliferation of lymphocytes to PLP was
      significantly reduced, together with a downregulation of interleukin (IL)-17 and
      a marked decrease of the IFN-gamma/IL-4 ratio. Immunohistochemical examination
      also disclosed a marked decrease of inflammatory cell infiltration, and
      attenuated demyelination and acute axonal transaction. These results may provide
      a rationale of selective blockade of Rho-kinase by oral use of fasudil as a new
      therapy for multiple sclerosis.

PMID- 16996143
TI  - Serum IgE reactive against small myelin protein-derived peptides is increased in
      multiple sclerosis patients.
AB  - Though independent findings suggest roles for the allergic arm of the immune
      system and myelin-reactive antibodies in MS, myelin-reactive IgE has not been
      investigated. We have developed a radioimmunoassay that measures reactive IgE,
      IgG and IgA against short (5-6-mers) myelin protein-derived peptides bearing
      little to no sequence identity with other human proteins, and which might
      therefore be targets of a CNS-specific autoimmune attack. Here we show that,
      irrespective of clinical subtype, MS patients' sera are characterized by a higher
      frequency of measurable IgE against the peptides. Moreover, in controls with
      measurable IgE reactive against test peptides, IgG or IgA reactive with the same
      peptide epitopes is almost always present in vastly greater quantities, whereas
      in MS subjects peptide-reactive IgA or IgG is often undetectable. The sensitivity
      of the full assay, when considering overall positive a serum sample that has
      detectable autoreactive IgE without other competing Igs, is 69% (S.E.: 5%), with
      a specificity of 87% (S.E.: 9%). We speculate that IgE reactive against CNS
      target antigens may have both diagnostic and pathogenic significance,
      particularly if other peptide-specific, potentially blocking Igs are absent.

PMID- 16996144
TI  - The dynamics of the LPS triggered inflammatory response of murine microglia under
      different culture and in vivo conditions.
AB  - Overall, the inflammatory potential of lipopolysaccharide (LPS) in vitro and in
      vivo was investigated using different omics technologies. We investigated the
      hippocampal response to intracerebroventricular (i.c.v) LPS in vivo, at both the
      transcriptional and protein level. Here, a time course analysis of interleukin-6
      (IL-6) and monocyte chemotactic protein-1 (MCP-1) showed a sharp peak at 4 h and
      a return to baseline at 16 h. The expression of inflammatory mediators was not
      temporally correlated with expression of the microglia marker F4/80, which did
      not peak until 2 days after LPS injection. Of 480 inflammation-related genes
      present on a microarray, 29 transcripts were robustly up-regulated and 90% of
      them were also detected in LPS stimulated primary microglia (PM) cultures.
      Further in vitro to in vivo comparison showed that the counter regulation
      response observed in vivo was less evident in vitro, as transcript levels in PM
      decreased relatively little over 16 h. This apparent deficiency of homeostatic
      control of the innate immune response in cultures may also explain why a group of
      genes comprising tnf receptor associated factor-1, endothelin-1 and schlafen-1
      were regulated strongly in vitro, but not in vivo. When the overall LPS-induced
      transcriptional response of PM was examined on a large Affymetrix chip,
      chemokines and cytokines constituted the most strongly regulated and largest
      groups. Interesting new microglia markers included interferon-induced protein
      with tetratricopeptide repeat (ifit), immune responsive gene-1 (irg-1) and
      thymidylate kinase family LPS-inducible member (tyki). The regulation of the
      former two was confirmed on the protein level in a proteomics study. Furthermore,
      conspicuous regulation of several gene clusters was identified, for instance that
      of genes pertaining to the extra-cellular matrix and enzymatic regulation
      thereof. Although most inflammatory genes induced in vitro were transferable to
      our in vivo model, the observed discrepancy for some genes potentially represents
      regulatory factors present in the central nervous system (CNS) but not in vitro.

PMID- 16996145
TI  - Vestibular evoked myogenic potentials in children.
AB  - OBJECTIVE: The aim of this work is to establish if the vestibular evoked myogenic
      potentials (VEMPs) could be used as a clinical test of vestibular function in
      children. MATERIALS AND METHODS: Forty normal hearing children, aged between 3
      and 15 years, and classified in preschool and scholar group, have been
      investigated in order to study normal development of vestibular potentials and to
      define fundamental parameters of VEMPs, establishing normal data of latencies and
      amplitude ratio. Electromyographic activity of sternocleidomastoid muscle was
      recorded while children were laid supine on a bed and asked to raise their head
      off of the bed in order to activate their neck flexors bilaterally. The saccular
      receptors were acoustically stimulated with a logon of 500Hz at an intensity of
      130dB peSPL presented monaurally through earphones. In each recording, we
      analysed latencies and amplitudes of the p13 and n23 waves and the amplitude
      ratio between the two ears. RESULTS: VEMPs were normally detected in all
      subjects. In preschool group mean p13 and mean n23 latencies were, respectively,
      16.13 (+/-2.12)ms and 21.17 (+/-2.77)ms; mean amplitude ratio was 28.49 (+/
      18.10). In scholar group mean p13 and n23 were respectively 16.14 (+/-3.48)ms and
      21.78 (+/-3.39)ms, while mean amplitude ratio 20.44 (+/-13.24). Comparison of
      latencies and amplitude ratio between the children groups and control adult group
      did not showed any significant differences. CONCLUSION: In conclusion, VEMPs
      could represent a valid and non-invasive technique able to investigate vestibular
      function in children and, in particular, vestibulo collic reflex.

PMID- 16996146
TI  - Further evidence that anxiety and memory are regionally dissociated within the
      hippocampus.
AB  - The hippocampus has been implicated in the regulation of anxiety and memory
      processes. Nevertheless, the precise contribution of its ventral (VH) and dorsal
      (DH) division in these issues still remains a matter of debate. The Trial 1/2
      protocol in the elevated plus-maze (EPM) is a suitable approach to assess
      features associated with anxiety and memory. Information about the spatial
      environment on initial (Trial 1) exploration leads to a subsequent increase in
      open-arm avoidance during retesting (Trial 2). The objective of the present study
      was to investigate whether transient VH or DH deactivation by lidocaine
      microinfusion would differently interfere with the performance of EPM-naive and
      EPM-experienced rats. Male Wistar rats were bilaterally-implanted with guide
      cannulas aimed at the VH or the DH. One-week after surgery, they received vehicle
      or lidocaine 2.0% in 1.0 microL (0.5 microL per side) at pre-Trial 1, post-Trial
      1 or pre-Trial 2. There was an increase in open-arm exploration after the intra
      VH lidocaine injection on Trial 1. Intra-DH pre-Trial 2 administration of
      lidocaine also reduced the open-arm avoidance. No significant changes were
      observed in enclosed-arm entries, an EPM index of general exploratory activity.
      The cautious exploration of potentially dangerous environment requires VH
      functional integrity, suggesting a specific role for this region in modulating
      anxiety-related behaviors. With regard to the DH, it may be preferentially
      involved in learning and memory since the acquired response of inhibitory
      avoidance was no longer observed when lidocaine was injected pre-Trial 2.

PMID- 16996147
TI  - Behavioral phenotyping of mouse models of neurodevelopmental disorders: relevant
      social behavior patterns across the life span.
AB  - Social responses are a key element for behavioral phenotyping of mouse models of
      neurodevelopmental disorders associated with social deficits. Here we describe
      selected behavioral responses that can be measured in developing and adult mice,
      with special emphasis on ultrasonic vocalizations, a behavioral response not yet
      systematically characterized in most of the genetic mouse models of social
      abnormalities. A recently developed task to measure social approach relevant to
      the first core symptom of autism is highlighted. We also focus on those
      developmental factors, including litter size, litter composition, and early
      social milieu, that are often underestimated when measuring adult social behavior
      in mouse models of neurodevelopmental disorders. We present a summary of
      available data concerning social behavioral responses in mice with targeted gene
      mutations. We conclude by suggesting that assessment of early behavioral traits,
      and corresponding relationships with adult behavioral profiles, could be a useful
      strategy to investigate mouse models of neurodevelopmental disorders associated
      with social deficits.

PMID- 16996148
TI  - Differential transcription profiles in Trypanosoma cruzi associated with clinical
      forms of Chagas disease: Maxicircle NADH dehydrogenase subunit 7 gene truncation
      in asymptomatic patient isolates.
AB  - The majority of individuals in the chronic phase of Chagas disease are
      asymptomatic (indeterminate form). Every year 2-3% of these individuals develop
      severe clinical manifestations (cardiac and digestive forms). In this study a
      Trypanosoma cruzi DNA microarray was used to compare the transcript profiles of
      six human isolates: three from asymptomatic and three from cardiac patients.
      Seven signals were expressed differentially between the two classes of isolates,
      including tryparedoxin, surface protease GP63, cyclophilin, some hypothetical
      proteins and the pre-edited maxicircle gene NADH dehydrogenase subunit 7 (ND7).
      The approximately 30-fold greater signal in cardiac strains for ND7 was the most
      pronounced of the group, and differential levels of pre-edited ND7 transcript
      confirmed the microarray analysis. The ND7 gene from asymptomatic isolates showed
      a deletion of 455bp from nt 222 to nt 677 relative to ND7 of the CL Brener
      reference strain. The ND7 gene structure correlated with disease manifestation
      for 20 isolates from clinically characterised, chronic phase patients. The ND7
      lesion produces a truncated product that could impair the function of
      mitochondrial complex I. Possible links between the integrity of the electron
      transport chain and symptom presentation are discussed. We propose that ND7 and
      other genes of the pathway constitute valuable targets for PCR assays in the
      differential diagnosis of the infective T. cruzi strain. While this hypothesis
      requires validation by the examination of additional recent parasite isolates
      from patients with defined pathologies, the identification of specific molecular
      markers represents a promising advance in the association between parasite
      genetics and disease pathology.

PMID- 16996149
TI  - Differential var gene transcription in Plasmodium falciparum isolates from
      patients with cerebral malaria compared to hyperparasitaemia.
AB  - The Plasmodium falciparum variant erythrocyte surface antigens known as PfEMP1,
      encoded by the var gene family, are thought to play a crucial role in malaria
      pathogenesis because they mediate adhesion to host cells and immuno-modulation.
      Var genes have been divided into three major groups (A, B and C) and two
      intermediate groups (B/A and B/C) on the basis of their genomic location and
      upstream sequence. We analysed expressed sequence tags of the var gene DBLalpha
      domain to investigate var gene transcription in relation to disease severity in
      Malian children. We found that P. falciparum isolates from children with cerebral
      malaria (unrousable coma) predominantly transcribe var genes with DBLalpha1-like
      domains that are characteristic of Group A or B/A var genes. In contrast,
      isolates from children with equally high parasite burdens but no symptoms or
      signs of severe malaria (hyperparasitaemia patients) predominantly transcribe var
      genes with DBLalpha0-like domains that are characteristic of the B and C-related
      var gene groups. These results suggest that var genes with DBLalpha1-like domains
      (Group A or B/A) may be implicated in the pathogenesis of cerebral malaria, while
      var genes with DBLalpha0-like domains promote less virulent malaria infections.

PMID- 16996150
TI  - Evidence for Somatostatin receptor 2 in thyroid tissue.
AB  - Somatostatin receptor scintigraphy has found considerable interest for imaging
      thyroid tumours. Recently, also therapeutic application of Somatostatin analogues
      labelled with beta-emitting radionuclides has been suggested as treatment option
      for thyroid tumours with absent radioiodine uptake. Most of the radiolabelled
      analogues available show a predominant affinity for Somatostatin receptor subtype
      2. This study reports on the in vitro characterisation of Somatostatin receptor
      subtype mRNAs in thyroid tumours and normal thyroid tissue by means of RT-PCR.
      Surgical samples of 21 patients were collected, and mRNA of 16 tumour and 17
      control specimen was isolated. mRNA expression for Somatostatin, SSTR subtype 1
      5, thyroid markers (NIS, TSH, Tg, TPO) and control markers (GAPDH, beta-actin)
      was determined. PCR results were correlated with immunohistochemistry staining
      using SSTR2 receptor specific antibodies. 94% of all samples expressed
      Somatostatin receptor mRNA with predominant expression of subtype 2, less
      predominant of subtype 5 and subtype 3. Somatostatin receptor subtype 2 mRNA
      expression correlated well with immunohistochemical staining pattern in 13/16
      samples, SSTR2 immunohistochemistry was positive in 87% of the samples. Our
      results show that Somatostatin receptor 2 is predominantly expressed on thyroid
      tissue and is a valid target for treatment of thyroid tumours. Octreotide
      derivatives currently used in Nuclear medicine seem to be well suited to target
      receptors expressed in thyroid tumours.

PMID- 16996151
TI  - Development of a novel bioavailable inhibitor of the calmodulin-regulated protein
      kinase MLCK: a lead compound that attenuates vascular leak.
AB  - Tissue barriers involving epithelial and endothelial cell layers are critical to
      homeostasis, regulating passage of water, macromolecules, cells and certain
      classes of small molecules via two distinct cellular mechanisms, transcellular or
      paracellular. Endothelial or epithelial barrier dysfunction is a key component of
      pathophysiology in diverse diseases and injuries that have a broad impact on
      survival and quality of life. However, effective and safe small molecule
      therapeutics for these disorders are lacking. Success in development would
      therefore fill a major unmet medical need across multiple disease areas. Myosin
      light chain kinase (MLCK), a highly specialized calcium/calmodulin (CaM)
      regulated protein kinase, modulates barrier function through its regulation of
      intracellular contractile processes. MLCK levels and activity are increased in
      various animal models of disease and in human clinical disease samples. Our prior
      work with a genetic knockout (KO) mouse strain for the long form of MLCK,
      MLCK210, has identified MLCK as a drug discovery target for endothelial and
      epithelial barrier dysfunction. We describe here the development of a selective,
      bioavailable, stable inhibitor of MLCK that attenuates barrier dysfunction in
      mice comparable to that seen with the MLCK KO mice. The inhibitor compound 6 is
      stable in human microsomal metabolic stability assays and can be synthesized in a
      high-yielding and facile synthetic process. These results provide a foundation
      for and demonstrate the feasibility of future medicinal chemistry refinement
      studies directed toward the development of novel therapies for disorders
      involving barrier dysfunction.

PMID- 16996152
TI  - Structural and functional consequences of c-N-Ras constitutively associated with
      intact mitochondria.
AB  - We demonstrate that both c-N-Ras and c-K(B)-Ras are constitutively associated
      with purified mitochondria. c-K(B)-Ras is associated with the mitochondrial outer
      membrane, and c-N-Ras is associated with both the outer membrane and inner
      mitochondrial compartments. The mitochondrial morphology is abnormal in both c-N
      Ras negative and K-Ras negative cells. Normal mitochondrial morphology was
      restored by targeting N-Ras to both the inner and outer mitochondrial
      compartments, or by ectopically expressing c-K(B)-Ras. Impaired mitochondrial
      function can result in increased CHOP and NFkappaB activity, typical for a
      retrograde signaling response. Both are constitutively elevated in the N-Ras
      negative cells, but not in the K-Ras negative background, and are restored by c-N
      Ras targeted exclusively to the inner mitochondrial compartment. Surprisingly,
      both targeting and the ability to functionally reduce retrograde transcriptional
      activity were found to be independent of c-N-Ras farnesylation. Overall, these
      data demonstrate for the first time a (1) farnesylation independent function for
      c-N-Ras and (2) that N-Ras within the inner mitochondrial compartment is an
      essential component of the retrograde signaling system between the mitochondria
      and nucleus.

PMID- 16996154
TI  - Effect of oligofructose supplementation on gut microflora and well-being in young
      children attending a day care centre.
AB  - The effect of daily administration of oligofructose (OF) on 7-19 months old
      healthy children intestinal microflora, intestinal tolerance and well-being was
      assessed in a double blind placebo controlled study. The study comprised 8 days
      of observation, 21 days of supplementation, and 15 days of post-supplementation.
      Exclusion criteria included antibiotic use and intake of other prebiotic and
      probiotic at any time following enrolment. Faecal flora was analysed by culture
      methods, and health information was recorded daily. Bifidobacteria, tended to
      slightly increase with OF supplementation, but not with placebo (p=0.095).
      Simultaneously, a decrease in potential pathogens, significant for clostridia
      (p=0.05) but not for staphylococci (p=0.09) was observed in the OF group. These
      modifications did not persist during the post-supplementation period. OF
      supplementation were accompanied by less flatulence, diarrhoea, vomiting
      (p<0.001), and fever (p<0.05) events.

PMID- 16996155
TI  - An alternative process for cleaning knives used on meat slaughter floors.
AB  - Traditionally on slaughter floors operator knives are cleaned by rinsing in hand
      wash water at 20-40 degrees C followed by brief immersion in baths termed
      "sterilisers" which contain water no cooler than 82 degrees C. Under Australian
      legislation, both domestic and export, it is possible for a meat processing
      establishment to apply to the Controlling Authority for permission to implement
      an alternative procedure providing that it is at least the equivalent of that
      legislated. No firm evidence appears to exist for the 82 degrees C requirement
      and the possibility of replacing this element of the knife cleaning procedure
      with an alternative procedure using 60 degrees C water and a longer immersion
      time was investigated at an abattoir slaughtering cattle and sheep. Knives were
      tested at a range of work stations located along beef and mutton slaughter floors
      for Aerobic Plate Counts (APCs) and E. coli. For knives used on the beef chain
      the mean log APC/cm(2) was 2.18 by the current knife cleaning process and 1.78 by
      the alternate procedure (P<0.001). Using the current system E. coli was isolated
      from cleaned knives on 20/230 (8.7%) occasions compared with 21/230 (9.1%)
      occasions using the alternative system. The mean log E. coli of positive knives
      was 0.43/cm(2) and 0.61/cm(2) from the current and alternative systems,
      respectively. On the mutton chain the mean log APC/cm(2) was 1.95 using the
      current knife cleaning process and 1.69 by the alternative procedure (P=0.014).
      Using the current system E. coli was isolated from cleaned knives on 24/130
      (18.5%) occasions compared with 29/130 (22.3%) occasions using the alternative
      system. The mean log E. coli of positive knives was 0.90/cm(2) and 0.76/cm(2)
      from the current and alternative systems, respectively. It is concluded that
      using two knives alternatively, rinsing them in hand wash water, then immersing
      them between uses in 60 degrees C water provides a microbiological outcome
      equivalent to rinsing them and momentary dipping in 82 degrees C water.

PMID- 16996153
TI  - Thy-1, a versatile modulator of signaling affecting cellular adhesion,
      proliferation, survival, and cytokine/growth factor responses.
AB  - Thy-1 is a 25-37 kDa glycosylphosphatidylinositol (GPI)-anchored protein involved
      in T cell activation, neurite outgrowth, apoptosis, tumor suppression, wound
      healing, and fibrosis. To mediate these diverse effects, Thy-1 participates in
      multiple signaling cascades. In this review, we discuss Thy-1 signaling primarily
      in non-immunologic cell types, including neurons, mesangial cells, ovarian cancer
      cells, nasopharyngeal carcinoma cells, endothelial cells, and fibroblasts. We
      review the current literature regarding Thy-1 signaling via integrins, protein
      tyrosine kinases, and cytokines and growth factors; and the roles of these
      signaling pathways in cellular adhesion, apoptosis, cell proliferation, and cell
      adhesion and migration. We also discuss the role of Thy-1 localization to lipid
      rafts, and of the GPI anchor in Thy-1 signaling. Ongoing research on the
      mechanisms of Thy-1 signaling will add to our understanding of the diverse
      physiologic and pathologic processes in which Thy-1 plays a role.

PMID- 16996156
TI  - Characterization of Listeria monocytogenes isolated from retail foods.
AB  - Listeria monocytogenes isolates recovered from retail ready-to-eat (RTE) meats,
      raw chickens and fresh produce were characterized by serogroup identification
      using PCR, genotyping using pulsed-field gel electrophoresis (PFGE) and
      antimicrobial susceptibility testing. Five L. monocytogenes serogroups were
      identified. Of the 167 isolates 68 (41%) belonged to serogroup 1/2b, 3b; 53 (32%)
      belonged to serogroup 4b, 4d, 4e; 43 (26%) belonged to serogroup 1/2a, 3a; 2
      (1.2%) belonged to serogroup 1/2c, 3c; and 1 (0.6%) belonged to serogroup 4a, 4c.
      PFGE generated 120 patterns which correlated well with PCR serogrouping. Most L.
      monocytogenes isolates were resistant to sulfonamide (73%) and some were
      resistant to tetracycline (8.4%) and ciprofloxacin (1.8%). Tetracycline
      resistance was conjugatively transferable and the tet(M) gene was identified in
      14 tetracycline-resistant isolates as well as their transconjugants. These
      findings indicate that L. monocytogenes present in food were diverse, and that
      resistance to one or more antibiotics among these isolates was common. In
      addition, the presence of potential serotype 4b in all food categories is of
      public health concern, as serotype 4b has been the serotype most frequently
      associated with human listeriosis.

PMID- 16996157
TI  - Surface binding of aflatoxin B1 by Saccharomyces cerevisiae strains with
      potential decontaminating abilities in indigenous fermented foods.
AB  - Saccharomyces cerevisiae constitutes one of the most important microorganisms
      involved in food fermentations throughout the world. Aflatoxin B(1) binding
      abilities of S. cerevisiae strains isolated from indigenous fermented foods from
      Ghana, West Africa were tested in vitro. Results show that aflatoxin binding was
      strain specific with 7 strains binding 10-20%, 8 strains binding 20-40% and 3
      strains binding more than 40% of the added aflatoxin B(1) when grown and
      incubated under standard conditions. Binding by two of the strains was further
      characterized. Highest binding capacity was seen with cells collected at the
      exponential growth phase with the strains A18 and 26.1.11 binding 53.0 and 48.8%
      of the total toxin respectively and the binding reduced towards the stationary
      phase. Aflatoxin B(1) binding increased steadily when the cells were incubated
      with 1 to 20 microg/ml of aflatoxin B(1). Binding was not affected by the cells
      grown at temperatures ranging from 20 to 37 degrees C, but was significantly
      reduced at 15 degrees C. Binding seems to be a physical phenomenon with cells
      treated at 52, 55 and 60 degrees C for 5 and 10 min or 120 degrees C for 20 min
      binding significantly higher quantities (more than 2-fold in 120 degrees C
      treated cells) of aflatoxin B(1) than their viable counterpart. Similarly, when
      the cells were treated with 2 M HCl for 1 h, up to 2-fold increase in binding was
      observed. The results obtained show that some strains of S. cerevisiae, viable or
      non-viable, are effective aflatoxin binders and these properties should be
      considered in the selection of starter cultures for relevant indigenous fermented
      foods where high aflatoxin level is a potential health risk.

PMID- 16996158
TI  - Studies on the interaction between grape-associated filamentous fungi on a
      synthetic medium.
AB  - Eleven fungi isolated from grapes and sun-dried grapes (Alternaria alternata,
      Cladosporium herbarum, Eurotium amstelodami, Penicillium janthinellum, P.
      decumbens, Trichoderma harzianum, Candida sp., Aspergillus carbonarius OTA
      negative, A. carbonarius OTA-positive, A. niger var. niger. and A. japonicus var.
      aculeatus), were grown in SNM medium at different water activities (0.82-0.97)
      and temperature (20-40 degrees C) levels for 18 days. Pairs of one Aspergillus
      faced with one non-Aspergillus were grown at 0.87-0.97 a(w) and at 20 and 30
      degrees C. In single cultures, daily radii were recorded. In paired cultures
      radii were recorded and each A. section Nigri isolate was given a dominance
      score. At high temperatures and low water activities, Penicillium isolates, E.
      amstelodami and A. niger var. niger showed higher growth rates, while T.
      harzianum only grew well at the highest water activity. In addition, A. section
      Nigri was dominant in most paired assays, being only surpassed by T. harzianum at
      0.97 a(w) and 20 degrees C. Thus, prevalence of A. section Nigri in sun-dried
      grapes can be explained by its adaptation to environmental conditions of sun
      drying, and by its capability to dominate other fungal species when coming into
      contact with them.

PMID- 16996159
TI  - Effects on Escherichia coli O157:H7 and meat starter cultures of bovine
      lactoferrin in broth and microencapsulated lactoferrin in dry sausage batters.
AB  - The effects of lactoferrin (LF) alone or with various chelating agents on the
      growth of 5 strains of Escherichia coli O157:H7 and 7 meat starter cultures were
      evaluated. E.coli O157:H7 and starter cultures were grown at 13 or 26 degrees C
      in Lauria (LB) or All Purpose Tween (APT) broths, respectively, with both broths
      being supplemented with 2.9% NaCl. LF alone prevented the growth of E. coli
      O157:H7 strains 0627 and 0628 but other strains grew. The antimicrobial
      effectiveness of LF was enhanced by EDTA but LF alone did not affect the growth
      of meat starter cultures in broth. However, when LF plus EDTA and sodium
      bicarbonate (SB) were used the growth of all meat starter cultures except
      Lactobacillus curvatus was reduced. During dry sausage manufacture with L.
      curvatus and Staphylococcus carnosus starter cultures the effects of LF,
      unencapsulated or microencapsulated in paste-like and dried powder forms, in
      sausage batters with or without EDTA and SB, on the viability of E. coli O157:H7
      were examined. The reduction of E. coli O157:H7 during sausage manufacture was
      significantly enhanced (p<0.05) by all LF treatments. The largest reduction (4.2
      log units) was obtained with unencapsulated LF. However, some of the apparent
      reduction in E.coli O157:H7 numbers with all treatments was due to cell injury
      rather than lethality, since significantly greater numbers were recovered on APT
      agar overlaid with the selective medium cefixime-tellurite Sorbitol McConkey agar
      (ct-SMAC) than on ct-SMAC alone. The narrow spectrum of LF activity and induction
      of injury rather than inactivation of E. coli O157:H7 limit the effectiveness of
      this agent against the pathogen in fermented meats.

PMID- 16996160
TI  - Hibernation, reversible cell growth inhibition by epigallocatechin-3-O-gallate.
AB  - Epigallocatechin-3-O-gallate (EGCg) and related polyphenolic compounds found in
      tea are known to have antioxidative activities. However, they also have pro
      oxidative activities such as generation of hydrogen peroxide. In this report, we
      investigated the effect on cells and showed the potential usage of EGCg in cell
      preservation. H(2)O(2) was generated from EGCg at concentrations of more than 300
      microg/mL for 6 h at 37 degrees C, and high cytotoxicity for L929 cells were
      shown. In contrast, in the presence of 1 microg/mL catalase, the amount of
      generated H(2)O(2) was significantly low and cytotoxicity decreased markedly.
      This indicates that catalase eliminated H(2)O(2) generated by degradation of
      EGCg. Although H(2)O(2) generation was prevented, L929 cell proliferation was
      slightly inhibited in proportion to the concentrations of EGCg. L929 was exposed
      able to be 300 microg/mL to EGCg and 1 microg/mL catalase for maximum 18 days.
      EGCg inhibited the growth of L929 cells, and cell proliferation was restarted
      immediately after medium change for removing EGCg. We concluded that EGCg had a
      reversible growth inhibition when H(2)O(2) was eliminated from cell cultures.

PMID- 16996162
TI  - Inhibition of peritoneal dissemination of tumor cells by single dosing of
      phosphodiester CpG oligonucleotide/cationic liposome complex.
AB  - Although unmethylated CpG dinucleotide-containing oligodeoxynucleotides (CpG ODN)
      are able to inhibit tumor metastasis through the induction of antitumor immunity,
      their stability and delivery to antigen presenting cells needs to be improved. In
      this study, we formulated a CpG ODN complex with cationic liposomes (CpG ODN
      lipoplex) and its antitumor activity was evaluated in peritoneal dissemination
      models of tumor cells stably labeled with firefly luciferase gene. A single
      intraperitoneal administration of CpG ODN-lipoplex greatly reduced the number of
      tumor cells to 0.01% or lower compared with that detected in untreated mice,
      which may be associated with increased production of TNF-alpha and IL-12. CpG ODN
      lipoplex increased the survival time of the tumor-bearing mice, and most long
      term survivors rejected rechallenged tumor cells. These results indicate that a
      single dosing of CpG ODN-lipoplex is effective in inhibiting peritoneal
      dissemination and inducing long-lasting antitumor immunity.

PMID- 16996161
TI  - On the influence of vector design on antibody phage display.
AB  - Phage display technology is an established technology particularly useful for the
      generation of monoclonal antibodies (mAbs). The isolation of phagemid-encoded mAb
      fragments depends on several features of a phage preparation. The aims of this
      study were to optimize phage display vectors, and to ascertain if different
      virion features can be optimized independently of each other. Comparisons were
      made between phagemid virions assembled by g3p-deficient helper phage,
      Hyperphage, Ex-phage or Phaberge, or corresponding g3p-sufficient helper phage,
      M13K07. All g3p-deficient helper phage provided a similar level of antibody
      display, significantly higher than that of M13K07. Hyperphage packaged virions at
      least 100-fold more efficiently than did Ex-phage or Phaberge. Phaberge's
      packaging efficiency improved by using a SupE strain. Different phagemids were
      also compared. Removal of a 56 base pair fragment from the promoter region
      resulted in increased display level and increased virion production. This
      critical fragment encodes a lacZ'-like peptide and is also present in other
      commonly used phagemids. Increasing display level did not show statistical
      correlation with phage production, phage infectivity or bacterial growth rate.
      However, phage production was positively correlated to phage infectivity. In
      summary, this study demonstrates simultaneously optimization of multiple and
      independent features of importance for phage selection.

PMID- 16996163
TI  - Protein diffusion in agarose hydrogel in situ measured by improved refractive
      index method.
AB  - The accurate knowledge of the diffusion behavior of protein within biomimetic
      hydrogel matrix at body temperature has a great implication for the design of
      efficient controlled release protein-base drug delivery devices. In this paper,
      we improved our previous in situ refractive index method with great temperature
      controlled capability. For the first time, this newly improved method was
      employed to study the diffusion of protein (bovine serum albumin (BSA) and
      lysozyme) in agarose hydrogel at body temperature (37 degrees C). The change of
      the gel refractive index caused by the change of the diffusing protein
      concentration within the gel during the diffusion process enables the effective
      diffusion coefficients of protein to be estimated. The diffusion coefficients of
      proteins decrease with the increase of the concentration of agarose and the
      solute molecular size. At the considered range of agarose concentration (0.5-3.0
      wt.%), the diffusion coefficients range from 4.98 to 8.21 x 10(-7) cm(2)/s for
      BSA and 1.15 to 1.56 x 10(-6) cm(2)/s for lysozyme, respectively. Temperature
      dependence of diffusivity of BSA in agarose hydrogel was also investigated.
      Furthermore, the retardance effect of polymer volume fraction on the diffusivity
      of both BSA and lysozyme in agarose hydrogels was analyzed with three models,
      Amsden's, Clauge and Philips', and Ogsten's model.

PMID- 16996164
TI  - Taurine in women with a history of gestational diabetes.
AB  - Taurine is the most abundant amino acid in the human body and seems to play an
      important role in increasing glucose-mediated insulin secretion, as well as in
      programming beta-cell maturation during the prenatal life in utero. To test the
      hypothesis that plasma taurine is related to glucose tolerance, insulin
      sensitivity and insulin secretion in subjects with history of beta-cell
      dysfunction such as women with history of gestational diabetes (GDM), we studied
      72 non-diabetic women with history of GDM (n=43), impaired glucose tolerance
      (IGT; n=7), and normal glucose tolerance (NGT; n=22) as previously classified by
      a 100g-3h-OGTT performed between the 24th and the 28th gestational week. Insulin
      sensitivity (ISIogtt, calculated through Matsuda-DeFronzo index) and a proxy for
      insulin secretion (basal plasma C-peptide/fasting plasma glucose; CP/glucose)
      were measured during and after pregnancy. Plasma taurine was measured after a
      median period of 6 years (2-11 years) from index pregnancy, when glucose
      tolerance was retested by a 75 g-2h-OGTT. Plasma taurine was significantly lower
      in women who had experienced GDM and was unrelated to ISIogtt. Moreover, plasma
      taurine was inversely related to previous gestational area-under-curve of glucose
      and directly related to post-gestational CP/glucose, as well to CP/glucose
      measured during pregnancy (p<0.05 for both). The relative risk of altered glucose
      metabolism during previous pregnancies (IGT+GDM) was higher as plasma taurine
      decreased, even after adjusting for age, time-lag from pregnancy, body mass index
      and family history of diabetes (OR: 0.980; CI 95%: 0.963-0.999, p=0.003). In
      conclusion plasma taurine seems to be a fair marker of altered glucose metabolism
      during past pregnancies in women with antecedent GDM and appears to be inversely
      related to the previous as well as to the actual insulin secretion in these
      subjects.

PMID- 16996165
TI  - Pemetrexed-induced edema of the eyelid.
AB  - Pemetrexed is a novel antimetabolite that targets multiple enzymes in the folate
      pathway, and has exhibited clear antitumor activities in the treatment of
      malignant pleural mesothelioma and non-small cell lung cancer. Although many
      adverse events of pemetrexed, such as bone marrow suppression, have been
      reported, edema of the eyelid has been previously reported in only one case
      (0.2%, n=519), according to the Pemetrexed Clinical Investigator's Brochure,
      April 2005 version. We experienced a patient who developed the valuable edema of
      the eyelid. We believe that medical oncologists should be aware of this rare
      adverse event, although the mechanism responsible for it is not yet known.

PMID- 16996166
TI  - Gefitinib as front-line treatment in Chinese patients with advanced non-small
      cell lung cancer.
AB  - PURPOSE: This phase II single arm, open label study was designed to evaluate the
      efficacy and toxicity of oral gefitinib (250mg) daily in previously untreated
      patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Eligible
      patients had stage IIIB or IV NSCLC with adequate organ functions, and were
      chemonaive. All eligible patients were treated with oral administration of 250mg
      of gefitinib until intolerable toxicity, disease progression or death occurred.
      Responses were assessed after every 8 weeks of therapy. RESULTS: For a total of
      53 patients, the objective response rate (ORR) was 32.1% and overall disease
      control rate (DCR) was 52.8%. Median overall and progression-free survivals (PFS)
      were 9.4 (95% CI, 8.8-13.3) and 3.2 months (95% CI, 1.1-5.2) months, and 1-year
      survival rate was 41.5%. Patients with adenocarcinoma (n=35) had a higher
      response rate. Adenocarcinoma, female gender (n=24), and response to gefitinib
      were predictive factors for better survival. The most commonly seen adverse
      events (AEs) were skin toxicity (54.7%), diarrhea (43.4%) and nail change
      (16.9%). Most AEs were mild to moderate and considered manageable. Drug-related
      interstitial pneumonia was clinically diagnosed in four cases (7.5%).
      CONCLUSIONS: Oral gefitinib, as compared to conventional chemotherapy, has
      comparable effect but less toxicity as a first-line treatment in Chinese patients
      who have advanced NSCLC, especially in those with adenocarcinoma histology. A
      further phase III prospective study comparing gefitinib to standard chemotherapy
      to define the efficacy of gefitinib is appropriate in advanced NSCLC patients.

PMID- 16996167
TI  - The prognostic impact of tumor size in resected stage I non-small cell lung
      cancer: evidence for a two thresholds tumor diameters classification.
AB  - PURPOSE: The current TNM staging system for non-small cell lung cancer subdivides
      stage IA and IB according to a tumor size threshold of 3 cm. Some authors have
      suggested that tumor size behaves as a continuous, but the optimal diameter
      thresholds to be adopted remain debated. METHODS: We conducted a retrospective
      study on 548 patients who underwent a complete surgical resection at our
      institute for stage IA and IB non-small cell lung cancer according to the current
      TNM staging system. Univariate and multiaviate analysis of overall and disease
      specific survival were performed. RESULTS: Stage IA had an overall 5 years
      survival of 67% and a 5 years disease-specific survival of 85%. Stage IB had an
      overall 5 years of 49% and 5 years disease-specific survival of 53%. Tumors <2 cm
      had a significantly better survival than tumors > or =2 cm (overall survival:
      p=0.007; disease-specific survival: p=0.026), as well as tumors ranging from 2 to
      5 cm in comparison with larger ones (overall survival: p=0.031; disease-specific
      survival: p=0.013). No significant difference was found between groups ranging
      from 2 to 5 cm. Tumors of 2-5 cm had 57% higher probability of death in
      comparison with tumors <2 cm and tumors >5 cm had a probability of death 60%
      higher than tumor of 2-5 cm. Age and tumor size (two thresholds diameter
      classification) resulted independent variables at multivariate analysis.
      CONCLUSION: the definition of T factor in the staging system of non-small cell
      lung cancer should consider two cutoffs according to tumor size. Two and 5 cm
      represent appropriate thresholds diameters that define subgroups with significant
      different prognosis.

PMID- 16996168
TI  - Stimulated release of calcitonin gene-related peptide from the human right atrium
      in patients with and without diabetes mellitus.
AB  - Calcitonin gene-related peptide (CGRP), a potent vasodilator released during
      activation from a subset of sensory Adelta- and C-fiber afferents, has been
      suggested to play a beneficial role in myocardial ischemia. Variations in CGRP
      release can possibly be correlated with diseases that involve changes in activity
      or degeneration of cardiac afferent fibers. The aim of the present study was to
      examine basal and stimulated CGRP release from cardiac tissue in patients who
      underwent cardiopulmonary bypass surgery and to compare patients with and without
      known history of diabetes mellitus. Small pieces of the right atrium routinely
      excised during the bypass operations were passed through series of oxygenated
      solutions. The TRPV1 receptor agonist capsaicin and the nitric oxide donor
      NONOate were added for stimulation of cardiac afferent fibers. The eluates were
      processed using an enzyme immuno-assay (EIA) for measurement of CGRP
      concentrations. Both capsaicin and NONOate caused significant increases in CGRP
      release. No significant differences in CGRP release between patients with and
      without diabetes mellitus were examined. The present study evaluates a simple and
      reproducible model for measuring stimulated CGRP release from the human right
      atrium.

PMID- 16996169
TI  - Synthesis, in vitro antiproliferative activities, and Chk1 inhibitory properties
      of indolylpyrazolones and indolylpyridazinedione.
AB  - The synthesis of 5-indolylpyrazol-3-one, 4-indolylpyrazol-3-one and 4-indolyl
      pyridazin-3,6-dione is reported. Their Chk1 inhibitory properties have been
      evaluated and their in vitro antiproliferative activities toward three tumor cell
      lines: murine leukemia L1210, human colon carcinoma HT29 and HCT116 have been
      determined. 4-Indolyl-pyridazin-3,6-dione is inactive against Chk1 and exhibits
      weak cytotoxicities toward the tumor cell lines tested. The IC(50) values toward
      Chk1 of the two indolylpyrazolones are identical and are in the micromolar range,
      but the cytotoxicities of 4-indolylpyrazol-3-one are significantly stronger than
      those of 5-indolylpyrazol-3-one. Since 4-indolylpyrazol-3-one and 5
      indolylpyrazol-3-one can present several conformers and tautomeric forms,
      molecular modelling in the ATP binding site of Chk1 has been carried out to
      investigate which form could induce the best stabilization in the active site of
      the enzyme. To get an insight into the kinase selectivity of these compounds,
      their inhibitory activities toward Src kinase were evaluated.

PMID- 16996170
TI  - [Ocular metastases heralding non-small cell lung cancer: two cases].
AB  - INTRODUCTION: Ocular metastases are rare in patients with lung cancer, and
      exceptionally indicate the condition. EXEGESIS: We report 2 patients with
      symptomatic ocular metastases indicating lung adenocarcinoma, involving the
      choroid in the first case and the optic disc in the other, associated with other
      metastases. No improvement of visual acuity was observed after chemotherapy and
      radiotherapy. DISCUSSION: Ocular metastases may indicate lung cancer, and are
      usually associated with other metastatic sites. The global prognosis is poor but
      an early treatment should result in improvement of visual prognosis.

PMID- 16996171
TI  - Perspective: How to evaluate studies on peri-operative nutrition? Considerations
      about the definition of optimal nutrition for patients and its key role in the
      comparison of the results of studies on nutritional intervention.
AB  - Different nutritional outcome studies on the same subject can have vast
      differences in composition of the chosen food without justification, suggesting
      that the composition of "optimal" nutrition in patients is not known or that
      optimal nutrition does not exist. The result will be negative studies which
      reinforces the existing impression that nutritional intervention is of limited
      value in every day's patient care. This perspective will put arguments forward
      that optimal nutrition exists and that the definition of optimal nutrition should
      be the base of future nutrition intervention studies. This perspective aims at
      providing a definition of optimal nutrition and consequently a basis to
      critically appraise the literature upon nutritional interventions in disease
      states.

PMID- 16996172
TI  - Peru-15, a live attenuated oral cholera vaccine, is safe and immunogenic in
      Bangladeshi toddlers and infants.
AB  - A live oral Vibrio cholerae O1 El Tor vaccine, Peru-15 was tested in a double
      blind, randomized placebo controlled study for safety and immunogenicity in Phase
      I and Phase II studies in 240 Bangladeshi children aged 9 months-5 years of age.
      Two different doses (2x10(7) and 2x10(8)cfu) were tested. Vaccination did not
      elicit adverse events and the strain was genetically stable. Vibriocidal antibody
      responses developed in 42/50 (84%) toddlers (2-5 years) and 35/50 (70%) of
      younger children (9-23 months) and overall 77/100 (77%) who received the high
      dose. LPS-IgA-antibody responses were seen in 60% of toddlers and 34% of infants;
      40% responded with IgA antibodies to cholera toxin. The responses to the reduced
      dose was lower. These studies demonstrate that Peru-15 at a dose of 2x10(8)cfu is
      safe and immunogenic in children in Bangladesh.

PMID- 16996173
TI  - Human antibody response towards the pneumococcal surface proteins PspA and PspC
      during invasive pneumococcal infection.
AB  - IgG antibodies against pneumococcal surface protein A, family 1 (PspA1) and
      family 2 (PspA2), protein C (PspC), and protein Hic were investigated in 41
      patients with invasive pneumococcal disease. Pre-existing antibody levels against
      the four pneumococcal proteins were not significantly different from those found
      in 40 patients with non-pneumococcal bacteremia or 80 healthy controls. However,
      during convalescense a strong immune response developed especially against PspA,
      and there was a high degree of cross-reactivity between PspA- and PspC
      antibodies. Our findings on immunogenicity and cross-reactivity suggest that in a
      future pneumococcal protein based vaccine, only a limited number of proteins
      could be sufficient.

PMID- 16996174
TI  - Dynamic responses of photosystem II in the Namib Desert shrub, Zygophyllum
      prismatocarpum, during and after foliar deposition of limestone dust.
AB  - The effects of limestone dust deposition on vegetation in desert ecosystems have
      not yet been reported. We investigated these effects in a succulent shrub from
      the Namib Desert at a limestone quarry near Skorpion Zinc mine (Namibia). Effects
      of limestone dust were determined in Zygophyllum prismatocarpum (dollar bush)
      plants with heavy, moderate and no visible foliar dust cover by means of
      chlorophyll a fluorescence measurements. Limestone dust deposition decreased
      overall plant performance through loss of chlorophyll content, inhibition of
      CO(2) assimilation, uncoupling of the oxygen-evolving complex and decreased
      electron transport. Importantly, dynamic recovery occurred after termination of
      limestone extraction at the quarry. Recovery was accelerated by rainfall, mainly
      because of dust removal from leaves and stimulation of new growth. These results
      indicate that limestone dust has severe effects on photosynthesis in desert
      shrubs, but that recovery is possible and that, in arid environments, this
      process is modulated by rainfall.

PMID- 16996175
TI  - Adsorption and redox reactions of heavy metals on synthesized Mn oxide minerals.
AB  - Several Mn oxide minerals commonly occurring in soils were synthesized by
      modified or optimized methods. The morphologies, structures, compositions and
      surface properties of the synthesized Mn oxide minerals were characterized.
      Adsorption and redox reactions of heavy metals on these minerals in relation to
      the mineral structures and surface properties were also investigated. The
      synthesized birnessite, todorokite, cryptomelane, and hausmannite were single
      phased minerals and had the typical morphologies from analyses of XRD and TEM/ED.
      The PZCs of the synthesized birnessite, todorokite and cryptomelane were 1.75,
      3.50 and 2.10, respectively. The magnitude order of their surface variable
      negative charge was: birnessite> or =cryptomelane>todorokite. The hausmannite had
      a much higher PZC than others with the least surface variable negative charge.
      Birnessite exhibited the largest adsorption capacity on heavy metals Pb(2+),
      Cu(2+), Co(2+), Cd(2+) and Zn(2+), while hausmannite the smallest one.
      Birnessite, cryptomelane and todorokite showed the greatest adsorption capacity
      on Pb(2+) among the tested heavy metals. Hydration tendency (pK(1)) of the heavy
      metals and the surface variable charge of the Mn minerals had significant impacts
      on the adsorption. The ability in Cr(III) oxidation and concomitant release of
      Mn(2+) varied greatly depending on the structure, composition, surface properties
      and crystallinity of the minerals. The maximum amounts of Cr(III) oxidized by the
      Mn oxide minerals in order were (mmol/kg): birnessite (1330.0)>cryptomelane
      (422.6)>todorokite (59.7)>hausmannite (36.6).

PMID- 16996176
TI  - Halophyte vegetation influences in salt marsh retention capacity for heavy
      metals.
AB  - We analysed concentrations of Cu, Cd and Pb in above and belowground tissues of
      the halophyte species Halimione portulacoides and Spartina maritima, as well as
      in sediments and pore water between the roots in a Tagus estuary salt marsh
      (Portugal). From these results we calculated the pools of metals in the
      compartments mentioned above. Relative percentages of accumulation in each pool
      were also determined. Our aim was to determine how the type of vegetation in the
      salt marsh affects overall metal retention capacity of the system. It was
      concluded that areas colonised by H. portulacoides are potential sources of Cu,
      Cd and Pb to the marsh ecosystem, whereas areas colonised by S. maritima are more
      effective sinks at least for Cu and Cd. Consequently, S. maritima seems to
      contribute more effectively to the stabilisation of metals in salt marsh
      sediments, reducing their availability to the estuarine system.

PMID- 16996177
TI  - Determination of selected antibiotics in the Victoria Harbour and the Pearl
      River, South China using high-performance liquid chromatography-electrospray
      ionization tandem mass spectrometry.
AB  - Nine selected antibiotics in the Victoria Harbour of Hong Kong and the Pearl
      River at Guangzhou, South China, were analyzed using high-performance liquid
      chromatography-electrospray ionization tandem mass spectrometry. The results
      showed that the concentrations of antibiotics were mainly below the limit of
      quantification (LOQ) in the marine water of Victoria Harbour. However, except for
      amoxicillin, all of the antibiotics were detected in the Pearl River during high
      and low water seasons with the median concentrations ranging from 11 to 67 ng/L,
      and from 66 to 460 ng/L, respectively; and the concentrations in early spring
      were about 2-15 times higher than that in summer with clearer diurnal variations.
      It was suggested that the concentrations of antibiotics in the high water season
      were more affected by wastewater production cycles due to quick refreshing rate,
      while those in the low water season may be more sensitive to the water column
      dynamics controlled by tidal processes in the river.

PMID- 16996178
TI  - Exemplifying whole-plant ozone uptake in adult forest trees of contrasting
      species and site conditions.
AB  - Whole-tree O3 uptake was exemplified for Picea abies, Fagus sylvatica and Larix
      decidua in stands at high and low altitude and contrasting water availability
      through sap flow measurement in tree trunks, intrinsically accounting for drought
      and boundary layer effects on O3 flux. O3 uptake of evergreen spruce per unit
      foliage area was enhanced by 100% at high relative to low elevation, whereas
      deciduous beech and larch showed similar uptake regardless of altitude. The
      responsiveness of the canopy conductance to water vapor and, as a consequence, O3
      uptake to soil moisture and air humidity did not differ between species. Unifying
      findings at the whole-tree level will promote cause-effect based O3 risk
      assessment and modeling.

PMID- 16996179
TI  - Mechanisms of silicon-mediated alleviation of abiotic stresses in higher plants:
      a review.
AB  - Although silicon (Si) is the second most abundant element both on the surface of
      the Earth's crust and in soils, it has not yet been listed among the essential
      elements for higher plants. However, the beneficial role of Si in stimulating the
      growth and development of many plant species has been generally recognized.
      Silicon is known to effectively mitigate various abiotic stresses such as
      manganese, aluminum and heavy metal toxicities, and salinity, drought, chilling
      and freezing stresses. However, mechanisms of Si-mediated alleviation of abiotic
      stresses remain poorly understood. The key mechanisms of Si-mediated alleviation
      of abiotic stresses in higher plants include: (1) stimulation of antioxidant
      systems in plants, (2) complexation or co-precipitation of toxic metal ions with
      Si, (3) immobilization of toxic metal ions in growth media, (4) uptake processes,
      and (5) compartmentation of metal ions within plants. Future research needs for
      Si-mediated alleviation of abiotic stresses are also discussed.

PMID- 16996180
TI  - Effect of physico-chemical pretreatment on the removal efficiency of horizontal
      subsurface-flow constructed wetlands.
AB  - In this study, we tested the effect of a physico-chemical pretreatment on
      contaminant removal efficiency in two experimental horizontal subsurface-flow
      constructed wetlands (SSF CWs). One SSF CW was fed with settled urban wastewater,
      whereas the other with the same wastewater after it had undergone a physico
      chemical pretreatment. The SSF CWs were operated with three different hydraulic
      retention times. During the experiments the effluent concentrations of COD,
      ammonia N and sulfate were very similar, and, therefore, the physico-chemical
      pretreatment did not improve the quality of the effluents. COD removal efficiency
      (as percentage or mass surface removal rate) was slightly greater in the SSF CW
      fed with pretreated wastewater. Ammonia N removal efficiency was, in general,
      similar in both SSF CWs and very high (80-90%). At the end of the experiments it
      was observed that in the SSF CW fed with settled wastewater the hydraulic
      conductivity decreased by a 20%.

PMID- 16996181
TI  - Modelling stomatal ozone flux and deposition to grassland communities across
      Europe.
AB  - Regional scale modelling of both ozone deposition and the risk of ozone impacts
      is poorly developed for grassland communities. This paper presents new
      predictions of stomatal ozone flux to grasslands at five different locations in
      Europe, using a mechanistic model of canopy development for productive grasslands
      to generate time series of leaf area index and soil water potential as inputs to
      the stomatal component of the DO(3)SE ozone deposition model. The
      parameterisation of both models was based on Lolium perenne, a dominant species
      of productive pasture in Europe. The modelled seasonal time course of stomatal
      ozone flux to both the whole canopy and to upper leaves showed large differences
      between climatic zones, which depended on the timing of the start of the growing
      season, the effect of soil water potential, and the frequency of hay cuts. Values
      of modelled accumulated flux indices and the AOT40 index showed a five-fold
      difference between locations, but the locations with the highest flux differed
      depending on the index used; the period contributing to the accumulation of AOT40
      did not always coincide with the modelled period of active ozone canopy uptake.
      Use of a fixed seasonal profile of leaf area index in the flux model produced
      very different estimates of annual accumulated total canopy and leaf ozone flux
      when compared with the flux model linked to a simulation of canopy growth.
      Regional scale model estimates of both the risks of ozone impacts and of total
      ozone deposition will be inaccurate unless the effects of climate and management
      in modifying grass canopy growth are incorporated.

PMID- 16996182
TI  - Metals and arsenic in soils and corresponding vegetation at Central Elbe river
      floodplains (Germany).
AB  - Floodplain soils at the Elbe river are frequently polluted with metals and
      arsenic. High contents of these pollutants were detected down to subsoil layers.
      NH4NO3-extractable (phytoavailable) Cd, Ni, and Zn were elevated in horizons with
      high acidity. Among five common floodplain plant species, Artemisia vulgaris
      showed highest concentrations of Cd, Cu, and Hg, Alopecurus pratensis of As and
      Phalaris arundinacea of Ni, Pb, and Zn. Relationships were weak between metal
      concentrations in plants and phytoavailable stocks in soil. As and Hg uptake
      seems to be enhanced on long submerged soils. Enrichments of Cd and Hg are linked
      to a special plant community composition. Grassland herbage sampled in
      July/August revealed higher concentrations of As (+122%), Hg (+124%), and Pb
      (+3723%) than in May. To limit harmful transfers into the food chain, low-lying
      terraces and flood channels revealing highest contaminations or
      phytoavailabilities should be excluded from mowing and grazing.

PMID- 16996183
TI  - Development and application of long-term sublethal whole sediment tests with
      Arenicola marina and Corophium volutator using Ivermectin as the test compound.
AB  - Short-term whole sediment tests using the amphipod Corophium volutator and the
      polychaete Arenicola marina are now routinely used in Europe to assess the acute
      toxicity of marine sediments. However, there is still a need to develop longer
      term assays which measure effects on sublethal endpoints that are more relevant
      to predicting impacts at the population level. The effect of increasing exposure
      times and measuring additional endpoints such as growth, on the sensitivity of
      these assays was investigated. The test compound used was the chemotherapeutant
      Ivermectin (IVM), used in aquaculture to treat sea lice infestations. IVM was
      found to be acutely toxic to both test organisms. Extending the lugworm test to
      100 days increased sensitivity of survival by a factor of three; a significant
      reduction in casting rate was observed at concentrations an order of magnitude
      lower. This assay shows potential for detecting the sublethal effects of low
      concentrations of sediment contaminants. Increasing the exposure time did not
      seem to affect the sensitivity of the amphipod, but further method development is
      required.

PMID- 16996184
TI  - Implications of research on endocrine disruption for the environmental risk
      assessment, regulation and monitoring of chemicals in the European Union.
AB  - We assess the implications which research on endocrine disrupting chemicals
      (EDCs) has for the regulation of synthetic substances and for the protection of
      the environment, particularly under the forthcoming European Union (EU) REACH
      legislation. EDCs present regulatory problems inter alia because they can act
      additively at concentrations which are individually harmless, and they may have
      non-classical dose (concentration)-response relationships at low exposure levels.
      Furthermore, current in vivo testing routines were not specifically designed to
      assess the endocrine disrupting properties of chemicals, whilst in silico and in
      vitro methods have only limited applicability and availability for this purpose.
      We need to ensure that the assessment approaches specified in the draft REACH
      legislation and Technical Guidance are able to evaluate EDCs efficiently.
      However, it must also be recognised that environmental monitoring procedures in
      Europe will need to be improved to detect EDCs that have evaded identification,
      and where appropriate, control, under REACH.

PMID- 16996185
TI  - Dietary exposure of children and teenagers to benzoates, sulphites,
      butylhydroxyanisol (BHA) and butylhydroxytoluen (BHT) in Beirut (Lebanon).
AB  - The acceptable daily intake (ADI) for a considered chemical is by definition the
      amount of that substance which can be ingested every day during the life time
      without appreciable health risk. The theoretical risk of exceeding the ADI for
      benzoates, sulphites, butylhydroxyanisol (BHA) and butylhydroxytoluen (BHT) has
      often been examined on the basis of worst case scenario. The aim of this paper is
      to assess the actual intake of the food additives listed above for a group of the
      Lebanese population (students aged between 9 and 18 years old) likely to be
      highly exposed to food additives through the consumption of processed foods.
      Dietary exposure was obtained by combining food consumption data with food
      additives levels determined by chemical analysis. Food products available in
      Lebanon and containing added benzoates, sulphites, BHA and BHT were identified.
      Overall 420 samples of foods and beverages were analysed. The determination of
      food additives residue levels was carried out according to the official methods
      adopted in "Lebanese Institute for agronomic research" (IRAL) on food as
      consumed. The acceptable daily intake (ADI) could be exceeded for sulphites and
      BHT by a fraction of the population, in particular within children of 9-13 years
      old. Among all food additive-containing foods, the highest contributors were:
      soft drinks to benzoates intake, nuts and canned juices to sulphites intake,
      bread and biscuits to BHA intake and chewing gum to BHT intake.

PMID- 16996186
TI  - Developing a cultural model for long-term female urinary incontinence.
AB  - The purpose of this study is to examine the subjective experience of long-term
      urinary incontinence and to show how a cultural model helps define that
      experience. Using a narrative approach within a cultural models framework, the
      specific aims are to describe and analyze: (1) what urinary incontinence means;
      and (2) how that meaning is constructed and negotiated by women living with
      urinary incontinence. 17 community-dwelling women (from Philadelphia, USA, and
      its immediate suburbs) participated in semi-structured interviews. Plot types and
      shared themes were compared with themes that emerged from media representations
      of female incontinence, and a cultural model was developed. Findings suggest: (1)
      the meaning of long-term female urinary incontinence is constructed and
      negotiated as a result of individual and shared experiences; (2) the cultural
      model constructed by women differs significantly from the professional, primarily
      biomedical model; and (3) women's narratives provide a method for accommodating
      similarities and differences between lay and professional models.

PMID- 16996187
TI  - Patient-physician racial and ethnic concordance and perceived medical errors.
AB  - In this paper, I use nationally representative survey data to examine the
      relationship between patient-physician racial/ethnic concordance and perceived
      medical errors in the USA. After adjusting for potential confounding factors, we
      find that White patients treated by White physicians have 33% lower odds of
      reporting medical errors than White patients treated by non-White physicians. In
      contrast, patient-physician racial/ethnic concordance has no effect on perceived
      medical errors among non-White patients. The results suggest that the role of
      racial/ethnic concordance in perceptions of health care safety varies by
      patients' racial/ethnic background.

PMID- 16996188
TI  - Effects of calmodulin and protein kinase C modulators on transient Ca2+ increase
      and capacitative Ca2+ entry in human platelets: relevant to pathophysiology of
      bipolar disorder.
AB  - Disturbed intracellular calcium (Ca(2+)) homeostasis has been implicated in
      bipolar disorder, which mechanisms may be involved in the dysregulation of
      protein kinase C (PKC) and calmodulin systems. In this study, we investigated a
      transient intracellular Ca(2+) increase induced by thapsigargin, an inhibitor of
      sarco/endoplasmic reticulum Ca(2+)-ATPase pump (SERCA), and a capacitative Ca(2+)
      entry followed by addition of extracellular Ca(2+), in the presence or absence of
      PKC/calmodulin modulators in the platelets of healthy subjects in order to
      elucidate the role of SERCA in Ca(2+) homeostasis and to assess how both PKC and
      calmodulin systems regulate the two Ca(2+) responses. Moreover, we also examined
      the thapsigargin-elicited transient Ca(2+) increase and capacitative Ca(2+) entry
      in patients with mood disorders. PKC and calmodulin systems have opposite
      regulatory effects on the transient Ca(2+) increase and capacitative Ca(2+) entry
      in the platelets of normal subjects. The inhibitory effect of PKC activation on
      capacitative Ca(2+) entry is significantly increased and the stimulatory effect
      of PKC inhibition is significantly decreased in bipolar disorder compared to
      major depressive disorder and normal controls. These results suggest the
      possibility that increased PKC activity may activate the inhibitory effect of
      capacitative Ca(2+) entry in bipolar disorder. However, this is a preliminary
      study using a small sample, thus further studies are needed to examine the PKC
      and calmodulin modulators on the capacitative Ca(2+) entry in a larger sample.

PMID- 16996189
TI  - A dose response study following in utero and lactational exposure to di-(2
      ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats.
AB  - The reproductive effects of in utero and lactational exposure to di-(2
      ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The
      selected endpoints included reproductive organ weights, testicular function,
      hormonal status, sexual behaviour and fertility. Two wide ranges of doses, low
      and high, were tested. Female Wistar rats were treated daily with DEHP and peanut
      oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low
      doses were 0.015, 0.045, 0.135, 0.405 and 1.215 mg DEHP/kg body weight (bw)/day,
      and the high-doses were 5, 15, 45, 135 and 405 mg DEHP/kg bw/day. A reduction in
      daily sperm production of 19-25% in relation to control was observed in animals
      exposed to 15, 45, 135 and 405 mg/kg/day. Quantitation of specific cell types
      shows that the observed effects in daily sperm production are not related to
      changes in the number of Sertoli cells or their capability to support early
      stages spermatocytes. A low incidence of cryptorchidism was observed in DEHP
      exposed groups with a lowest observed adverse effect level of 5mg/kg/day. Serum
      testosterone concentration was similar to control at most doses but was
      significantly increased at 0.045, 0.405 and 405 mg DEHP/kg/day. In spite of this
      effect, the weight of seminal vesicle with coagulating glands was significantly
      reduced at 405 mg/kg/day. Testis, epididymis and prostate weights were similar
      among groups. Fertility and sexual behaviour were not affected by DEHP treatment
      at any dose. Overall, our results show that in utero and lactational DEHP
      exposure reduces daily sperm production and has the potential to induce
      reproductive tract abnormalities (of which cryptorchidism seems to be the most
      sensitive in our rat strain) in male offspring rats. The lowest observed adverse
      effect levels (LOAELs) for these effects were 15 and 5 mg/kg/day, respectively.
      Therefore, the no observed adverse effect level (NOAEL) for this study can be set
      at 1.215 mg/kg/day.

PMID- 16996190
TI  - Modulation of aromatase activity and mRNA by various selected pesticides in the
      human choriocarcinoma JEG-3 cell line.
AB  - Aromatase enzyme plays a central role in steroidogenesis by converting androgens
      to estrogens and has been proposed as an important molecular target for many
      environmental endocrine disrupters chemicals. In this study, we have screened 30
      selected pesticides with known, unknown or supposed effects on aromatase
      activity, for their ability to modulate aromatase activity in the human
      choriocarcinoma JEG-3 cell line after both short (2 h) and long exposure (24 h).
      All pesticides were tested at concentrations up to 10 microM that did not cause
      cytotoxicity after 24h of exposure, as verified by the MTT viability assay. Four
      pesticides inhibited aromatase activity after 2 h of exposure: prochloraz
      (IC(50)<1 microM), fenbuconazole (IC(50)=1.1 microM), propiconazole (IC(50)=1.5
      microM) and fenarimol (IC(50)=3.3 microM). Among them, prochloraz and
      fenbuconazole also exerted inhibitory effects after 24h. Toxaphen (10 microM) and
      heptachlor (10 microM) inhibited aromatase activity after 24h exposure only. Nine
      pesticides induced aromatase activity: aldrin, chlordane, cypermethrin, parathion
      methyl, endosulfan, methoxychlor, oxadiazon, metolachlor and atrazine after 24 h
      of exposure, while tributyltin induced aromatase activity at 1 nM and 3 nM after
      both 2 h and 24 h of exposure, respectively. To further investigate the
      mechanisms of aromatase induction we measured CYP19 mRNA expression and showed
      that methoxychlor, aldrin, chlordane and tributyltin induced the transcription of
      the cyp19 gene. In addition, none of the aromatase inducers transactivated the
      retinoic acid receptor (RAR) in JEG-3 stably transfected with a RARE-luciferase
      plasmid while the RAR agonist TTNPB induced both aromatase and luciferase
      expression in these cells. Our results, which provide new data for fenbuconazole,
      as an inhibitor of human aromatase, and for eight pesticides as aromatase
      inducers, are discussed with regards to the regulation of aromatase expression in
      the JEG-3 cellular context.

PMID- 16996191
TI  - Effects of storage time and temperature on the properties of two self-etching
      systems.
AB  - OBJECTIVES: To evaluate the micro-shear bond strength to enamel and dentin, pH
      and hardness of two self-etching adhesives over a period of 60 weeks storage at
      different temperatures. MATERIALS AND METHODS: Two self-etching systems, an all
      in-one adhesive, Clearfil Tri-S Bond (TS) and a two-step adhesive, Clearfil SE
      Bond (SE) were used in this study (both by Kuraray Medical, Osaka, Japan). Their
      micro-shear bond strengths to enamel and dentin were measured. The materials were
      then stored at 4, 23 or 37 degrees C. Their bond strengths were measured again
      after 1, 4, 16 and 60 weeks and compared to the base line. The nano-indentation
      hardness of the polymerized bonding, pH of SE primer and TS were also measured at
      the baseline and after 60 weeks of storage at three different temperatures. Bond
      strength and hardness data were analyzed using ANOVA and post hoc tests at the
      significance level of 0.05. RESULTS: Two-way ANOVA analysis showed that both
      storage conditions and material type had significant effects on bond strength to
      enamel or dentin but the interactions of these factors were not significant for
      any of the substrates. One-way ANOVA post hoc tests revealed that the bond
      strength of adhesives stored at 37 degrees C significantly decreased during the
      storage period; with the earliest significant decreases observed at 4 weeks for
      TS and at 16 weeks for SE. After 60 weeks of storage, the hardness obtained for
      SE bonding resin was not significantly different with that at the baseline for 4,
      23 and 37 degrees C groups, but there was a significant decrease observed in
      hardness for TS stored at 37 degrees C, compared to that at the baseline. The pH
      of both self-etching materials decreased when they were stored at 37 degrees C.
      CONCLUSION: Storage time and temperature significantly affected the bond strength
      of both materials through the time dependent hydrolysis and other changes that
      are likely to occur in the water-containing self-etching agents at high
      temperatures.

PMID- 16996192
TI  - Phosphorylation of Rho-associated kinase (Rho-kinase/ROCK/ROK) substrates by
      protein kinases A and C.
AB  - Rho-associated kinase (Rho-kinase/ROCK/ROK) is a serine/threonine kinase and
      plays an important role in various cellular functions. The cAMP-dependent protein
      kinase (protein kinase A/PKA) and protein kinase C (PKC) are also
      serine/threonine kinases, and directly and/or indirectly take part in the signal
      transduction pathways of Rho-kinase. They have similar phosphorylation site
      motifs, RXXS/T and RXS/T. The purpose of this study was to identify whether sites
      phosphorylated by Rho-kinase could be targets for PKA and PKC and to find peptide
      substrates that are specific to Rho-kinase, i.e., with no phosphorylation by PKA
      and PKC. A total of 18 substrates for Rho-kinase were tested for phosphorylation
      by PKA and PKC. Twelve of these sites were easily phosphorylated. These results
      mean that Rho-kinase substrates can be good substrates for PKA and/or PKC. On the
      other hand, six Rho-kinase substrates showing no or very low phosphorylation
      efficiency (<20%) for PKA and PKC were identified. Kinetic parameters (K(m) and
      k(cat)) showed that two of these peptides could be useful as substrates specific
      to Rho-kinase phosphorylation.

PMID- 16996193
TI  - New insights into the regulation of phytochelatin biosynthesis in A. thaliana
      cells from metabolite profiling analyses.
AB  - In higher plants and some fungi, heavy metals induce the synthesis of chelating
      peptides known as phytochelatins (PCs). They are characterized by the general
      structure (gamma-Glu-Cys)n-Gly, but in some plant species, the C-terminal glycine
      can be replaced by serine, glutamine, glutamate or alanine, leading to iso
      phytochelatins (iso-PCs). Although the distribution of iso-PCs is considered to
      differ from one species to another, we previously showed that Arabidopsis
      thaliana (A. thaliana) cells are able to synthesize most PC-related peptides (PCs
      and iso-PCs) described in the literature. We also observed an accumulation of the
      dipeptide gamma-glutamylcysteine (gamma-EC) when cadmium (Cd) (200 microM) was
      added to the culture medium, suggesting that either glutathione synthetase or
      glycine availability could be a limiting factor for the biosynthesis of PC
      related peptides. In this context, the aim of the present work was to seek new
      insights into the regulation of PC synthesis by performing metabolic profiling
      using liquid chromatography-mass spectrometry. The levels of PC-related peptides
      and their precursors were measured in A. thaliana cells following Cd exposure. A
      range of doses (0, 50, 200 and 400 microM CdNO3) and kinetic studies (from 1 to
      48 h) showed a dose threshold (50 microM CdNO3) and a lag time between the
      appearance of PCs and iso-PCs concomitant with the gamma-EC accumulation induced
      by Cd, occurring at cadmium concentrations above 50 microM. This accumulation was
      suppressed by supplementation of the culture medium with 25 mM glycine. Glycine
      supplementation had a limited impact on the concentrations of glutathione and PCs
      whereas the levels of most iso-PCs were significantly increased. Taken together,
      these results indicate that GSH is involved in the biosynthesis of the iso-PCs in
      vivo, and that the biosynthesis of PC-related peptides is limited by the
      availability of glycine in the presence of high cadmium concentrations.

PMID- 16996194
TI  - A randomised controlled trial of the effect of biphasic or monophasic waveform on
      the incidence and severity of cutaneous burns following external direct current
      cardioversion.
AB  - OBJECTIVE: Cutaneous burns are a common cause of morbidity following direct
      current (DC) cardioversion. We designed a prospective randomised double-blinded
      controlled study to determine the effect of biphasic or monophasic waveform on
      the pain and inflammation occurring after elective cardioversion. MATERIALS AND
      METHODS: One hundred and thirty nine patients undergoing elective DC
      cardioversion were randomised to receive monophasic (HP Codemaster XL; 100, 200,
      300, 360, and 360 J) or biphasic (Welch Allyn-MRL PIC defibrillator; 70, 100,
      150, 200, and 300 J) waveforms. Two hours after DC cardioversion, skin
      temperature, erythema index and sensory threshold to light and sharp touch was
      measured at the centre and edge of paddle sites. Visual analogue pain score (VAS)
      was recorded at 2 and 24 h. RESULTS: There was significantly less pain following
      biphasic cardioversion as assessed by VAS at both 2 h (p < 0.001; 95% confidence
      intervals of difference of medians (CI) 0.2-0.8 cm) and 24 h (p = 0.004; 95% CI
      0.0-0.4 cm). There was significantly less erythema in patients receiving biphasic
      cardioversion at the edge of the sternal site (p = 0.046; 95% CI 0.41-4.5). There
      was no difference in any other variable at any site between biphasic and
      monophasic cardioversion. CONCLUSION: The use of a biphasic waveform for DC
      cardioversion reduces the inflammation and pain of burns as measured by erythema
      index and visual analogue scale.

PMID- 16996195
TI  - Severe virilisation in a 71-year-old acromegalic woman with probable polycystic
      ovary syndrome.

PMID- 16996196
TI  - Influence of mode of delivery on neonatal mortality and morbidity in spontaneous
      preterm breech delivery.
AB  - OBJECTIVE: To study the association between mode of delivery and neonatal outcome
      in singleton pregnancy with breech presentation and preterm birth, due to
      premature labour (PTL) and/or preterm premature rupture of the membranes (pPROM).
      DESIGN AND METHODS: Information on preterm (gestational week 25-36) singleton
      births in breech presentation in Sweden during 1990-2002 was obtained from the
      Swedish Medical Birth Registry and the Swedish Hospital Discharge Registry. The
      study groups included 1975 caesarean and 699 vaginal deliveries with a diagnosis
      of PTL or pPROM, without pregnancy complications implying a high risk of fetal
      compromise. The rates of infant respiratory distress syndrome (IRDS),
      intraventricular haemorrhage (IVH), low Apgar scores, and neonatal deaths were
      compared between infants delivered vaginally and by caesarean section. Odds
      ratios were calculated with adjustment for gestational age, year of birth,
      maternal age and parity. RESULTS: The risk of neonatal death and the risk of an
      Apgar score below 5 min postnatally were both lower after caesarean delivery (OR
      0.4; 95% CI 0.2-0.7, and OR 0.4; 95% CI 0.3-0.7, respectively), whereas the risk
      of IRDS was increased (OR 2.1; 95% CI 1.4-3.2). A diagnosis of IRDS was not
      associated with mortality (OR 0.8; 95% CI 0.5-1.5). IVH was not associated with
      mode of delivery (OR 1.2; 95% CI 0.5-2.8). CONCLUSION: The lower neonatal
      mortality after CS supports a policy of caesarean delivery of the preterm breech.

PMID- 16996197
TI  - Application of game theory for a groundwater conflict in Mexico.
AB  - Exploitation of scarce water resources, particularly in areas of high demand,
      inevitably produces conflict among disparate stakeholders, each of whom may have
      their own set of priorities. In order to arrive at a socially acceptable
      compromise, the decision-makers should seek an optimal trade-off between
      conflicting objectives that reflect the priorities of the various stakeholders.
      In this study, game theory was applied to a multiobjective conflict problem for
      the Alto Rio Lerma Irrigation District, located in the state of Guanajuato in
      Mexico, where economic benefits from agricultural production should be balanced
      with associated negative environmental impacts. The short period of rainfall in
      this area, combined with high groundwater withdrawals from irrigation wells, has
      produced severe aquifer overdraft. In addition, current agricultural practices of
      applying high loads of fertilizers and pesticides have contaminated regions of
      the aquifer. The net economic benefit to this agricultural region in the short
      term lies with increasing crop yields, which requires large pumping extractions
      for irrigation as well as high chemical loading. In the longer term, this can
      produce economic loss due to higher pumping costs (i.e., higher lift
      requirements), or even loss of the aquifer as a viable source of water. Negative
      environmental impacts include continued diminishment of groundwater quality, and
      declining groundwater levels in the basin, which can damage surface water systems
      that support environmental habitats. The two primary stakeholders or players, the
      farmers in the irrigation district and the community at large, must find an
      optimal balance between positive economic benefits and negative environmental
      impacts. In this paper, game theory was applied to find the optimal solution
      between the two conflicting objectives among 12 alternative groundwater
      extraction scenarios. Different attributes were used to quantify the benefits and
      costs of the two objectives, and, following generation of the Pareto frontier or
      trade-off curve, four conflict resolution methods were then applied.

PMID- 16996198
TI  - Estimating the reduction of urban PM10 concentrations by trees within an
      environmental information system for planners.
AB  - Trees have been widely quoted as effective scavengers of both gaseous and
      particulate pollutants from the atmosphere. Recent work on the deposition of
      urban aerosols onto woodland allows the effect of tree planting strategies on
      airborne aerosol concentrations to be quantified and considered within the
      planning process. By identifying the potential planting locations in the local
      authority area, and applying them within a dispersion and deposition model, the
      potential magnitude of reduction in the ambient concentration of PM(10),
      achievable through urban tree planting, has been quantified for two UK cities. As
      part of the Environmental Information Systems for Planners (EISP), flow diagrams,
      based on planning decisions, have incorporated output from the model to make
      decisions on land use planning ranging from development plans and strategic
      planning, to development control. In this way, for any new developments that
      contribute to the local PM(10) level, the mitigation by planting trees can be
      assessed, and in some cases, reductions can be sufficient to meet air quality
      objectives for PM(10).

PMID- 16996199
TI  - Response to environmental flows in the lower Tarim River, Xinjiang, China: ground
      water.
AB  - In China's west since the 1950s large-scale ecosystem degeneration has occurred
      through water diversions for agricultural purposes. Since 2000, 1038 x 10(6) m(3)
      of water have been released into the Tarim River with the result that water
      reached the terminal Taitema Lake for the first time in 30 years. This
      environmental flow raised water-table levels along 350 km of the river. To assess
      the response of the water-table, a comparison "pristine" site is compared with
      downstream monitored sites. The results show huge changes in water-table levels.
      The study verifies that the water-table is extremely responsive to environmental
      flows, that strong internal similarities exist along the length of the river, and
      that the effect on the water-table and hence likely riparian vegetation recovery
      can be tentatively predicted. The actual impacts of the restoration strategy are
      less than those originally expected politically, socially and within the
      scientific community. We make recommendations on more effective release
      strategies.

PMID- 16996200
TI  - Stress urinary incontinence and the future of urology.

PMID- 16996201
TI  - Limitations of radioguided surgery in high-risk prostate cancer.
AB  - OBJECTIVES: To determine how many men with high-risk prostate cancer (prostate
      specific antigen [PSA]>20 ng/ml or biopsy Gleason score 8-10) have positive lymph
      nodes (sentinel lymph nodes [SLNs] and nonsentinel lymph nodes [NSLNs]) and
      whether these positive nodes are localised in the region of SLN dissection or in
      other regions, too. METHODS: In 228 men with high-risk prostate cancer radical
      retropubic prostatectomy combined with radioguided pelvic lymph node dissection
      and extended lymphadenectomy were performed. Serial sections of the SLNs were
      analysed immunohistochemically. RESULTS: A median of 7 SLNs (mean, 7) and 11
      NSLNs (mean, 11) were dissected per patient. Ninety-six of 228 men (42.1%) had
      lymph node metastases. Most men had positive lymph nodes along the internal iliac
      artery alone or in combination with other regions. Twenty-two men had only
      micrometastatic disease. In 94 of 96 men the SLNs were positive. Twenty-six of 96
      men had also positive NSLNs. When SLNs and NSLNs were positive, in more than half
      the patients the NSLNs were localised outside the region of sentinel
      lymphadenectomy. CONCLUSIONS: The dissection of SLNs in prostate cancer has a
      high sensitivity in detecting positive nodes. When SLNs are negative, the other
      pelvic lymph nodes are also negative in a high percentage of men (sensitivity
      97.1%). When the SLNs are positive, patients with high-risk disease also have a
      high incidence of positive NSLNs. Therefore, when it is aspired to remove all
      pelvic lymph node metastases sentinel and extended lymphadenectomy should be
      performed.

PMID- 16996202
TI  - Interview with Professor Peter Albers: treatment developments in testicular
      cancer. Interview by Christine McKillop.

PMID- 16996203
TI  - Differential expression and antibacterial activity of WFDC10A in the monkey
      epididymis.
AB  - The ability of the epididymis to perform its diverse functions stems from its
      regionalized gene and protein expression patterns. The differences in the gene
      expression patterns of the caput and cauda regions of the bonnet monkey
      epididymis were compared using the technique of differential display reverse
      transcriptase polymerase chain reaction. A transcript showing homology to human
      whey acidic protein 10 (hWFDC10A) was highly expressed in the monkey caput
      region. A peptide P2 was designed spanning a region of the monkey WFDC10A
      (mWFDC10A), which could inhibit the growth of gram-negative bacterial strains of
      Escherichia coli. P2 could permeabilize the bacterial cell membrane but was
      unable to permeabilize mammalian cells as evidenced by the lack of hemolysis upon
      incubation with the peptide. Expression of genes such as mWFDC10A may be
      essential in providing the first line of defense against microbial infections to
      the epididymal tract and thus rendering protection to the male gametes sheltered
      within the epididymis.

PMID- 16996204
TI  - BRCA1 and TP53 mutation spectrum of breast carcinoma in an ethnic population of
      Kashmir, an emerging high-risk area.
AB  - Breast cancer shows geographical variation in its incidence, even within areas of
      ethnic homogeneity. Kashmir valley (India), over past few years, witnesses an
      increase in incidence and occurrence of familial, early onset, and male breast
      cancer in its unexplored ethnic population. Here, we make a preliminary attempt
      to estimate the nature and frequency of BRCA1 and TP53 gene mutations of breast
      cancer patients from Kashmir. PCR-SSCP analysis followed by direct sequencing
      revealed the presence of only two germline intronic variations (c.199+67T>C and
      c.5396+187T>C) in BRCA1 gene in only 5.26% (2/38) patients while as 44% (11/25)
      of sporadic breast cancer patients harboured significant amount of somatic
      mutations in TP53 (p=0.0074; OR=0.053). The 17 mutations found in TP53 in 11
      patients, comprised of 13 substitutions [11 single-base (9 transitions+2
      transversions), 1 double-base and 1 complex] and four insertions. The 11
      substitutions represent missense mutations, leading to aminoacid substitution
      while as rest two were silent mutations. The four insertions represented three
      frame-shifts and one non-sense mutation. The mutation effect data was found to be
      significant (p=0.0002). Significant amount of mutations were found in exon 6
      (p=0.04; OR=0.273) and a combination of exons 6 and 7 (p=0.0145; OR=14.22) of
      TP53. Comparison of mutation profile with other ethnic populations and regions
      reflected both differences and similarities indicating co-exposure to a unique
      set of risk factors. The differences could be due to exposure to particular
      environmental carcinogens; different lifestyle, reproductive pattern; dietary or
      cultural practices of Kashmiri women that need further investigations. The
      infrequent presence of germline BRCA1 mutations in our study agree with the idea
      that a great proportion of moderate risk breast cancer population could be due to
      the susceptibility genes distinct from BRCA1. However, high frequency of somatic
      TP53 gene mutations implicates TP53 as a predominant factor for breast
      carcinogenesis in moderate risk ethnic Kashmiri population. The study also
      suggests TP53 as a potential molecular marker and prognostic tool, at least in a
      subset of sporadic breast tumors.

PMID- 16996205
TI  - Insulin-like growth factor-1 receptor and ligand targeting in head and neck
      squamous cell carcinoma.
AB  - IGF-1 receptor (IGF-1R) signaling is associated with increased tumorigenesis of
      epithelial cancers. In light of recent epidemiological studies correlating high
      circulating levels of IGF-1 with increased risk of second primary tumors (SPTs)
      of the head and neck, we examined IGF system and epidermal growth factor receptor
      (EGFR) expression in human head and neck squamous cell carcinoma (HNSCC) matched
      pairs and a cross-section of HNSCC cell lines. Employing the latter, we
      demonstrated that IGF-1 stimulated S-phase transition in a PI 3-K/Akt and Erk
      dependent manner in 5 of 8 cell lines, with Erk activation being dependent upon
      EGFR kinase activity. IGF-1 stimulated thymidine incorporation was inhibited by
      treatment with IGFBP-3, the IGF-1R tyrosine kinase inhibitor NVP-AEW541, or the
      EGFR tyrosine kinase inhibitor AG1478. Combining IGFBP-3 with NVP-AEW541 or
      AG1478 abrogated IGF-1 responses at 10-fold lower doses than either compound
      alone. These results demonstrate the potential for co-targeting the IGF system
      and EGFR in HNSCC.

PMID- 16996206
TI  - Resveratrol impairs the formation of MDA-MB-231 multicellular tumor spheroids
      concomitant with ceramide accumulation.
AB  - Resveratrol exerts a drastic growth inhibitory effect on human breast cancer MDA
      MB-231 cells grown both in vitro and in vivo. Here we show that resveratrol
      affects the aggregation properties of MDA-MB-231 cells into multicellular tumor
      spheroids (MCTSs), in association with induction of de novo synthesis of
      ceramide. After 9 days of 3D growth in the presence of resveratrol (64 microM),
      MDA-MB-231 cells formed significantly smaller MCTSs. Further, cells from these
      aggregates failed to form colonies. Addition of resveratrol (64 microM) to
      preformed MDA-MB-231 MCTSs caused no significant size change, consistent with
      lack of ceramide induction. Only some apoptotic blebs were found on the MCTSs
      surface. Altogether these findings indicate that resveratrol might be effective
      for prevention of breast cancer cell growth.

PMID- 16996207
TI  - Filtration of dust in a circulating granular bed filter with conical louver
      plates (CGBF-CLPs).
AB  - A novel circulating granular bed filter with conical louver plates (CGBF-CLPs)
      was designed to remove dust particulates from the flue gas stream of a coal power
      plant. The purpose of this investigation was to evaluate the performance of the
      CGBF-CLPs. Dust collection efficiency and pressure drop data were analyzed to
      determine better operating conditions. The effect of solid mass flow rate,
      collector particle size and dust/collector particles separator types on the dust
      collection efficiency and pressure drop in the CGBF-CLPs were investigated in
      this study. The solid mass flow rate (B) varied from 15.59+/-0.44 to 20.36+/-0.68
      g s(-1) and the initial average collector particle sizes were 1500 and 795
      microm, respectively. Two types of separators, a cyclone and an inertial one, for
      separating the dust and collector particles were used in the CGBF-CLPs system. An
      Air Personal Sampler (SKC PCXR8) was used to determine the inlet and outlet dust
      concentrations. A differential pressure transmitter and data acquisition system
      were used to measure the pressure drop. Experimental results showed that the
      highest dust collection efficiency was 99.59% when the solid mass flow rate was
      17.08+/-0.48 g s(-1) and the initial average collector particle size was 795
      microm with the cyclone type separator. The results showed that the attrition
      fines of the original collector particles returning to the granular bed filter
      (GBF) reduced bed voidage. This phenomenon significantly increased the dust
      collection efficiency in the CGBF-CLPs. As a consequence, a bigger bed voidage
      creates a lower dust collection efficiency in the GBF.

PMID- 16996208
TI  - Environmental hazard analysis and effective remediation of highway seepage.
AB  - Risk assessment and minimisation of environmental hazards are critical issues to
      consider in the geotechnical engineering projects. A case of highway pavement
      seepage induced by groundwater, at a locality along the section of Hua-Qing
      Highway of Guangdong Province, China, is presented for environmental hazard
      analysis and effective remediation. The environmental hazard analyses were based
      on in situ hydrogeologic investigation, rock-soil testing and integrated
      environmental understanding. The analyses indicate that the highway seepage was
      caused by elevation of groundwater hydraulic pressure in low permeable strata
      near the highway pavement, which was controlled by landform, hydrology, weather
      and road structure. The risk source of groundwater 'flooding' was the groundwater
      and surface water in the ring-like valley around Fenshui Village. A blind-ditch
      system for effective remediation of the pavement seepage hazard was proposed and
      successfully implemented by declining groundwater table near the highway based on
      the comprehensive assessment of various conditions. This geotechnical accident
      shows that the role of groundwater is an essential factor to consider in the
      geotechnical and environmental engineering studies and multidisciplinary effort
      for risk assessment of environmental hazards is important under current global
      climate change condition.

PMID- 16996209
TI  - Dechlorination of auto shredder residues.
AB  - Dechlorination of ASR (auto shredder residual) wastes has been studied in the
      present work. ASR was predechlorinated with Ca(OH)(2) extraction as well as
      dechlorinated with Ca(OH)(2) during incineration or pyrolysis. Experimentally,
      pre-dechlorination of ASR via extraction of Cl with a Ca(OH)(2) solution (pH
      12.5) may reduce Cl contain in the ASR by 15%. Extraction of Cl at elevated
      temperatures (such as 373 K), interestingly, led to a further reduction of Cl in
      the ASR to 33.5%. A small amount of HCl and light hydrocarbons (C(1)-C(5)) were
      yielded during pyrolysis of the ASR in the presence of Ca(OH)(2) at 773 K. On the
      contrary, 75-85% of Cl may be mineralized (CaCl(2)) with Ca(OH)(2) (or CaO)
      during incineration at 1100 K.

PMID- 16996210
TI  - Effect of noise on the contrast detection threshold in visual perception.
AB  - It has recently been shown that noise can improve the detection of stimuli in
      several sensory modalities. We herein investigated whether visual contrast
      detection sensitivity can be improved by adding a certain amount of noise. The
      contrast detection thresholds of a light changing brightness periodically were
      measured either with or without overlapping noise in 22 normal participants.
      Sinusoidal modulating light at 1 or 15 Hz was used as a signal. White noise was
      used to produce random flickering light as the noise. Participants were required
      to detect any changes in the brightness of the signal with or without noise. The
      contrast detection threshold, which was measured using a psychophysical method,
      decreased at around the threshold level of the noise intensity. The maximum
      facilitatory effect was obtained at a noise intensity of 5 dB. This effect was
      consistently observed regardless of the frequency of the signal (1 and 15 Hz).
      These findings indicate that noise can improve the signal detection in human
      visual perception.

PMID- 16996211
TI  - Effects of high dose of simvastatin on levels of dopamine and its reuptake in
      prefrontal cortex and striatum among SD rats.
AB  - Statins are increasingly being used for the treatment of a variety of conditions
      beyond their original indication for cholesterol lowering. We previously reported
      that simvastatin increased dopamine receptors in the rat prefrontal cortex [Q.
      Wang, W.L. Ting, H. Yang, P.T. Wong, High doses of simvastatin upregulate
      dopamine D(1) and D(2) receptor expression in the rat prefrontal cortex: possible
      involvement of endothelial nitric oxide synthase, Br. J. Pharmacol. 144 (2005)
      933-939] and restored its downregulation in a model of Parkinson's disease (PD)
      [Q. Wang, P.H. Wang, C. McLachlan, P.T. Wong, Simvastatin reverses the
      downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex
      of 6-hydroxydopamine-induced Parkinsonian rats, Brain Res. 1045 (2005) 229-233].
      Here we explore the effects of simvastatin treatment on tissue dopamine content
      and reuptake. Sprague-Dawley rats were given simvastatin (1 and 10 mg kg(-1)day(
      1), p.o.) for 4 weeks. Brain tissue from prefrontal cortex and striatum were
      taken out for dopamine content and its reuptake. Using high-performance liquid
      chromatographic-mass spectrometer (HPLC-MS), simvastatin (10 mg kg(-1)day(-1))
      was found to increase dopamine content by 110% in the striatum but decreased by
      76% in the prefrontal cortex compared with the saline treated group. Dopamine
      (DA) reuptake was unchanged in both brain regions. These results suggest that
      chronic treatment with high dose of simvastatin may affect DA tissue level in
      prefrontal cortex and striatum without changing on DA reuptake. This may have
      important clinical implications in psychiatric and striatal dopaminergic
      disorders.

PMID- 16996212
TI  - Quantitative comparison of image contrast and pattern between experimental and
      simulated high-resolution transmission electron micrographs.
AB  - Aiming to determine the contrast mismatch factor i.e. the Stobbs factor between
      the experimental and simulated high-resolution transmission electron micrographs,
      we have systematically compared the experimental images and simulations of a
      cleaved silicon sample for a series of focal settings and specimen thicknesses.
      For zero-loss energy filtered images, a mismatch factor of about 1.5-2.3 is
      measured for the image contrast, where the mismatch factor is focal dependent and
      higher mismatch appears around the focus value of 10nm. Attention is also given
      to the effects of the sample vibration and drift to the image contrast and
      pattern of the high-resolution micrographs.

PMID- 16996213
TI  - Quantification of the size-dependent energy gap of individual CdSe quantum dots
      by valence electron energy-loss spectroscopy.
AB  - Valence electron energy-loss spectroscopy (VEELS) performed in a monochromated
      scanning transmission electron microscope was used to measure the energy gaps of
      individual quantum dots (QDs). The gap energies of a series of CdSe QDs measured
      by VEELS reveal the expected quantum confinement effect; the gap energy increases
      with decreasing particle size. However, the values derived from these first VEELS
      measurements of single QDs are larger than the values commonly measured by
      optical spectroscopy. As standard optical methods lack the spatial resolution to
      probe individual nanoparticles, the particle-size distribution influences the
      optical response. It is suggested that the impact of the particle-size
      distribution accounts for the discrepancy between the energy-gap values derived
      from VEELS of single QDs and from optical methods of ensembles of QDs.

PMID- 16996214
TI  - Clinical and parasitological evaluation of dogs naturally infected by Leishmania
      (Leishmania) chagasi submitted to treatment with meglumine antimoniate.
AB  - Aiming to evaluate the efficacy of the treatment of canine visceral
      leishmaniasis, to verify the occurrence of a possible disease relapse, and to
      search for the presence of the parasites after the end of the treatment, seven
      dogs naturally infected by Leishmania (Leishmania) chagasi were used. The dogs
      were subjected to a treatment with 75 mg/kg meglumine antimoniate subcutaneously
      every 12 h for 21 days, and followed-up for a period of 6 months. During the
      whole experimental period the animals wore deltamethrin collars and were kept in
      a screened kennel to avoid reinfection. Lymph node and bone marrow aspiration
      biopsy was carried out to search for the parasite at seven moments: before the
      treatment, 30, 60, 90, 120, 150 and 180 days after the start of the treatment.
      After the end of the experiment all dogs were humanely euthanized. Then, spleen
      and liver "imprints" and in vitro cultures were carried out to search for
      amastigote forms of the parasite. During the treatment all animals presented
      remission of symptoms. However, two dogs were observed to present new symptoms in
      the course of the experiment. At the end of the experiment, the presence of
      amastigote forms of the parasite was evidenced in five of the seven dogs. This
      enabled us to conclude that the treatment promoted clinical cure but did not
      eliminate the parasites completely.

PMID- 16996215
TI  - Restriction and expansion of Ehrlichia strain diversity.
AB  - Ehrlichia are tick-borne gram negative, obligately intracellular bacteria. The
      16S rRNA gene DNA sequences are highly conserved among strains of each Ehrlichia
      species. The 28-kDa/Map-1 outer membrane protein genes are highly diversified
      among strains of Ehrlichia chaffeensis and E. ruminantium, but are highly
      conserved among E. canis isolates. The diversity of the immunodominant proteins
      of E. chaffeensis and E. ruminantium in contrast with the conservation of the
      immunodominant proteins of E. canis suggests that E. chaffeensis and E.
      ruminantium face more host immune pressure than E. canis or that E. chaffeensis
      and E. ruminantium evolved earlier than E. canis and have diverged.

PMID- 16996216
TI  - Down-regulation of ABCB1 transporter by atorvastatin in a human hepatoma cell
      line and in human peripheral blood mononuclear cells.
AB  - PURPOSE: The effect of atorvastatin, an HMG-CoA reductase inhibitor, on
      expression and activity of the drug transporter ABCB1 in HepG2 cells and
      peripheral blood mononuclear cells (PBMCs) was examined. METHODS: Localization
      and expression of ABCB1 in hepatocytes was examined by indirect
      immunofluorescence. Expression of ABCB1 mRNA and ABCB1 activity were examined in
      atorvastatin-treated and control cells and PBMCs using real-time PCR and
      Rhodamine 123 efflux assay. RESULTS: Immunohistochemical analysis revealed that
      ABCB1 is located at the apical membrane of the bile canaliculi. Atorvastatin at
      10 and 20 microM up-regulated ABCB1 expression resulting in a significant 1.4
      fold increase of the protein levels. Treatment of HepG2 cells with 20 microM
      atorvastatin caused a 60% reduction on mRNA expression (p<0.05) and a 41%
      decrease in ABCB1-mediated efflux of Rhodamine123 (p<0.01) by flow cytometry.
      Correlation was found between ABCB1 mRNA levels and creatine kinase (r=0.30;
      p=0.014) and total cholesterol (r=-0.31; p=0.010). CONCLUSIONS. Atorvastatin
      leads to decreased ABCB1 function and modulates ABCB1 synthesis in HepG2 cells
      and in PBMCs. ABCB1 plays a role in cellular protection as well as in secretion
      and/or disposition, therefore, inhibition of ABCB1 synthesis may increase the
      atorvastatin efficacy, leading to a more pronounced reduction of plasma
      cholesterol.

PMID- 16996217
TI  - Expression of ezrin in glial tubes in the adult subventricular zone and rostral
      migratory stream.
AB  - Ezrin is a member of the ERM (ezrin-radixin-moesin) family of membrane
      cytoskeletal linking proteins. ERM proteins are involved in a wide variety of
      cellular functions including cell motility, signal transduction, cell-cell
      interaction and cell-matrix recognition. A recent in situ hybridization study
      showed that the mRNA encoding ezrin is expressed in neurogenic regions of the
      mature brain including the subventricular zone (SVZ) and rostral migratory stream
      (RMS); however, the specific cell types expressing ezrin and their relationship
      to migrating and proliferating cells in these regions have not been characterized
      previously. In this study, we used immunocytochemistry to perform double labeling
      with a variety of cell-type specific markers to characterize the expression of
      ezrin in the SVZ and RMS of adult mice. Ezrin was expressed at high levels in
      both the SVZ and RMS where ezrin-immunopositive processes formed a trabecular
      network surrounding the proliferating and migrating cells. Ezrin-positive cells
      co-labeled with the glial makers S100beta and GFAP (glial fibrillary acidic
      protein), but only minimally with the early neuronal markers beta III tubulin and
      polysialylated form of neural cell adhesion molecule 1 (PSA-NCAM), indicating
      that ezrin was expressed primarily in the glial tube cells. Ezrin positive cells
      also expressed beta-catenin, a membrane-complex protein previously implicated in
      the regulation of stem-cell proliferation and neuronal migration. Glial tube
      cells act as both precursors of, and a physical channel for, migrating
      neuroblasts. Bi-directional signals between glial tube cells and migrating
      neuroblasts have been shown to regulate the rates of both proliferation of the
      precursor cells and migration of the newly generated neuroblasts. Our finding
      that ezrin and beta-catenin are both present at the cell membrane of the glial
      tube cells suggests that these proteins may be involved in those signaling
      processes.

PMID- 16996218
TI  - Glial cell line-derived neurotrophic factor-mediated enteric neuronal survival
      involves glycogen synthase kinase-3beta phosphorylation and coupling with 14-3-3.
AB  - Glial cell line-derived neurotrophic factor (GDNF) promotes the growth and
      survival of enteric neurons, but the mechanisms involved are poorly understood.
      GDNF is known to promote the survival of enteric neurons through activation of
      the PI3-Kinase/Akt signaling pathway. We investigated the role of glycogen
      synthase kinase-3beta (GSK-3beta) in enteric neuronal survival, and the ability
      of GDNF to regulate the activity of GSK-3beta using primary rat embryonic enteric
      neurons. GDNF, through activation of the PI3-kinase pathway enhanced the
      phosphorylation of GSK-3beta at its N-terminal serine-9 residue, and promoted the
      association of GSK-3beta with 14-3-3. Transfection of a constitutively active S9A
      GSK-3beta mutant prevented the survival effects of GDNF, whereas a dominant
      negative GSK-3beta construct prevented GDNF withdrawal-induced cell death.
      Increased GSK-3beta activity was associated with an increase in tau
      phosphorylation. Thus, GDNF promotes enteric neuronal survival by modulating GSK
      3beta and its downstream target tau. Inhibitors of GSK-3beta activity may have
      therapeutic potential in improving enteric neuronal survival.

PMID- 16996219
TI  - Effects of electrical stimulation of the raphe area on the micturition reflex in
      cats.
AB  - The raphe nucleus has a variety of physiological functions, including emotion,
      regulation of skeletal muscle motoneurons, spinal transmission of nociceptive
      signals, sleep, respiration, gastric motility, and cardiovascular function.
      Recent evidence has shown that centrally administered serotonin has modulatory
      effects on micturition function, and that decreased brain serotonin might
      underlie depression and an overactive bladder. We applied high-frequency
      stimulation (HFS; 0.2-ms duration, 100 Hz) in the raphe nucleus and the adjacent
      midline area in 20 supracollicular decerebrate cats, which mostly elicited
      inhibition of the micturition reflex. The effective amplitude of the electrical
      stimulation for evoking inhibitory responses was less than 50 muA. We also
      examined single neuronal activities in the raphe nucleus in response to
      isovolumetric spontaneous micturition reflexes. In total, 79 neurons were
      recorded in the raphe nucleus that were related to urinary storage/micturition
      cycles. Of the neurons recorded, the most common were tonic storage neurons
      (48%), followed by tonic micturition neurons (28%), phasic storage neurons (18%),
      and phasic micturition neurons (6%). In addition to the tonic/phasic as well as
      storage/micturition classification, the neurons showed diverse discharge
      patterns: augmenting, constant and decrementing, with the constant discharge
      pattern being most common. Among neurons in the raphe nucleus, the neurons with a
      decrementing discharge pattern were concentrated in the rostral portion, whereas
      the augmenting and constant neurons existed diffusely. The storage and
      micturition neurons were intermingled in the rostral portion, whereas they were
      separate in the caudal portion. In conclusion, the results of the present study
      indicate that HFS of the raphe area inhibits the micturition reflex and that
      there are micturition-related neuronal firings in the raphe area in cats,
      suggesting that the raphe nucleus is involved in neural control of micturition.

PMID- 16996220
TI  - Midbrain pathways for prepulse inhibition and startle activation in rat.
AB  - The midbrain is essential for prepulse inhibition (PPI) of the startle reflex,
      but the exact neural circuits for PPI are not yet determined. Electrical
      stimulation of the superior colliculus (SC) or pedunculopontine tegmentum was
      used to characterize the neurons and pathways that mediate PPI and the activation
      of startle that also occurs at higher currents in the same sites. Startle was
      inhibited by prepulses in most, but not all SC sites, with the lowest intensity
      sites in intermediate layers of SC. PPI latencies in SC sites were 4-6 ms longer
      than in inferior colliculus, intercollicular nucleus or pedunculopontine sites.
      Contrary to previous serial models, there must be two parallel midbrain pathways
      for PPI, a faster auditory pathway from inferior colliculus to pedunculopontine
      tegmentum, and a slower multimodal SC output for PPI. Double-pulse stimulation of
      SC sites shows that PPI results from direct stimulation of neurons with moderate
      refractory periods (0.4-1.0 ms), similar to SC neurons that mediate contraversive
      turning responses. By contrast, startle activation occurring at higher currents
      in all SC sites (even sites where PPI could not be elicited) results from
      stimulation of very short refractory period neurons (0.3-0.5 ms) and very long
      refractory period neurons (1.0-2.0 ms), with startle inhibition often found from
      0.5-1.0 ms. Startle activation appears to result from stimulation of short
      refractory period neurons in deep SC layers that mediate fear-potentiated
      startle, plus long refractory period substrates in more dorsal SC sites.

PMID- 16996221
TI  - Excitatory action of hypocretin/orexin on neurons of the central medial amygdala.
AB  - The neurons of the lateral hypothalamus that contain hypocretin/orexin (hcrt/orx)
      are thought to promote arousal through the excitatory action they exert on the
      multiple areas to which they project within the CNS. We show here that the
      hcrt/orx peptides can also exert a strong action on the amygdala, a structure
      known for its implication in emotional aspects of behavior. Indeed, the hcrt/orx
      peptides, applied in acute rat brain slices, excite a specific class of "low
      threshold burst" neurons in the central medial (CeM) nucleus which is considered
      as a major output of the amygdala. These excitatory effects are postsynaptic,
      mediated by Hcrt2/OX2 receptors and result from the closure of a potassium
      conductance. They occur on a class of neurons that are also excited by
      vasopressin acting through V1a receptors. These results suggest that the hcrt/orx
      system can act through the amygdala to augment arousal and evoke the autonomic
      and behavioral responses associated with fear, stress or emotion.

PMID- 16996222
TI  - Determinants of the differential gating properties of Cav3.1 and Cav3.3 T-type
      channels: a role of domain IV?
AB  - We have investigated the channel structural determinants that underlie the
      difference in gating properties of Cav3.1 and Cav3.3 T-type channels, by creating
      a series of chimeric channel constructs in which the major transmembrane domains
      were swapped. The chimeras were then expressed in tsA-201 cells and subjected to
      whole cell patch clamp analysis. Our data reveal that domains I and IV are major
      determinants of the half-activation potential. Substitution of domain IV was the
      most important determinant of activation time constant and time constant for
      recovery from inactivation, with domains I and II mediating a smaller role. In
      contrast, the carboxy terminal region did not appear to be involved. Determinants
      of the time constant for inactivation could not be localized to a specific
      transmembrane domain, but the concomitant substitution of domains I+IV was able
      to partially confer the inactivation kinetics among the two wild type channels.
      Our data indicate that the domain IV region mediates an important role in T-type
      channel activation, whereas multiple channel structural determinants appear to
      control T-type channel inactivation.

PMID- 16996223
TI  - Retinal projections to the subcortical visual system in congenic albino and
      pigmented rats.
AB  - The primary visual pathway in albino mammals is characterized by an increased
      decussation of retinal ganglion cell axons at the optic chiasm and an enhanced
      contralateral projection to the dorsal lateral geniculate nucleus. In contrast to
      the primary visual pathway, little is known about the organization of retinal
      input to most nuclei of the subcortical visual system in albino mammals. The
      subcortical visual system is a large group of retinorecipient nuclei in the
      diencephalon and mesencephalon. These areas mediate a range of behaviors that
      include both circadian and acute responses to light. We used a congenic strain of
      albino and pigmented rats with a mutation at the c locus for albinism (Fischer
      344-c/+; LaVail MM, Lawson NR (1986) Development of a congenic strain of
      pigmented and albino rats for light damage studies. Exp Eye Res 43:867-869) to
      quantitatively assess the effects of albinism on retinal projections to a number
      of subcortical visual nuclei including the ventral lateral hypothalamus (VLH),
      ventral lateral preoptic area (VLPO), olivary pretectal nucleus (OPN), posterior
      limitans (PLi), commissural pretectal area (CPA), intergeniculate leaflet (IGL),
      ventral lateral geniculate nucleus (vLGN) and superior colliculus (SC). Following
      eye injections of the neuroanatomical tracer cholera toxin-beta, the distribution
      of anterogradely transported label was measured. The retinal projection to the
      contralateral VLH, PLi, CPA and IGL was enhanced in albino rats. No significant
      differences were found between albino and pigmented rats in retinal input to the
      VLPO, OPN and vLGN. These findings raise the possibility that enhanced
      retinofugal projections to subcortical visual nuclei in albinos may underlie some
      light-mediated behaviors that differ between albino and pigmented mammals.

PMID- 16996225
TI  - Adult attachment security and college student substance use.
AB  - Previous research has demonstrated strong links between quality of adult
      attachment styles and various forms of psychological distress. A burgeoning
      literature further points to a relationship between insecure attachment and drug
      use, particularly alcohol consumption. In the present study, we expanded upon the
      existing literature by examining the relationship between adult attachment style
      and use of cigarettes, alcohol, and marijuana in a sample of 212 college
      students. Moreover, based on our previous work [Hankin, B.L., Kassel, J.D., and
      Abela, J.R.Z. (2005). Adult attachment dimensions and specificity of emotional
      distress symptoms: prospective investigations of cognitive risk and interpersonal
      stress generation as mediating mechanisms. Personality and Social Psychology
      Bulletin, 31, 136-151.], we proposed a conceptual model positing that adult
      attachment style influences both frequency of drug use and stress-motivated drug
      use through its impact on dysfunctional attitudes and self-esteem. Initial
      correlational analyses indicated significant (positive) associations between
      anxious attachment (tapping neediness and fear of abandonment) and both drug use
      frequency and stress-motivated drug use. Simultaneous regression analyses
      revealed that, for drug use frequency, the influence of anxious attachment
      operated primarily through its effect on dysfunctional attitudes and self-esteem.
      Regarding drug use attributable to negative affect reduction, anxious attachment
      demonstrated direct, independent effects on both cigarette smoking and alcohol
      use. These findings highlight the potential importance of adult attachment styles
      as a risk factor for drug use among college students.

PMID- 16996224
TI  - Abstinence rates following behavioral treatments for marijuana dependence.
AB  - Previous studies have noted particular difficulty in achieving abstinence among
      those who are marijuana dependent. The present study employed a dismantling
      design to determine whether adding contingency management (ContM) to motivational
      enhancement therapy plus cognitive behavioral therapy (MET+CBT), an intervention
      used in prior studies of treatment for marijuana dependence, would enhance
      abstinence outcomes. 240 marijuana dependent participants were recruited via
      advertisements and assigned to either MET+CBT, ContM-only, MET+CBT+ContM, or to a
      case-management control condition. All interventions involved 9 weekly 1-h
      sessions, except for the ContM-only condition whose sessions lasted about 15 min.
      ContM provided reinforcement for marijuana-free urine specimens, in the form of
      vouchers redeemable for goods or services. Follow-up data were collected at
      posttreatment and at 3-month intervals for 1 year. The two ContM conditions had
      superior abstinence outcomes: ContM-only had the highest abstinence rates at
      posttreatment, and the MET+CBT+ContM combination had the highest rates at later
      follow-ups. The roles of contingency management and coping skills training in the
      treatment of marijuana dependence are discussed.

PMID- 16996226
TI  - Thiazolidinedione anti-cancer activity: Is inhibition of microtubule assembly
      implicated?
AB  - An hypothesis is presented which seeks to explain the anti-cancer activity of
      thiazolidinediones (TZDs), a class of drugs currently used to treat type 2
      diabetes mellitus. Empirical data from the scientific literature is used to
      support the hypothesis that TZDs are inhibitors of microtubule assembly. The
      similarities between the affects of TZDs on cellular processes and known
      inhibitors of tubulin polymerization are identified. Similarities between TZDs
      and currently used inhibitors of microtubule assembly, such as cell cycle arrest
      in G1 phase, anti-angiogenesis activity, and inhibition of cell motility, are
      striking. In addition to the similarities in biological function, certain
      molecular structure similarities are also identified. The possibility that TZDs
      inhibit the polymerization of actin is presented as an alternative interpretation
      of the available data. Finally suggestions for testing the hypothesis, by using
      commercially available tubulin polymerization assays and fluorescence based
      binding assays, as well as isothermal titration calorimetry, are given.
      Considering TZD position as third-line therapy for treatment of type 2 diabetes
      mellitus and the potential loss of market share to newly introduced inhalable
      insulin, a better understanding of TZD anti-cancer activity may lead to revival
      for this drug class in cancer treatment.

PMID- 16996227
TI  - Schizophrenic speech as a disordered trajectory in a collapsed cognitive "Small
      World".
AB  - New theoretical instruments, as goal-directed neural networks models and
      geometric representations based on semantic graphs, open new approaches for our
      understanding of the schizophrenic speech. The neuropathologic disorders of the
      schizophrenia can be simulated using neural models, and these models can
      eventually explain the origin of goal confusion and incoherence in the
      schizophrenic discourse trajectory. Moreover, these models are useful to evaluate
      the different hypothesis about the pathogenic mechanisms of the disease. At the
      same time, a geometric representation of the trajectory of the speech can be
      obtained from real data. Our conjecture is that a context-dependent graph can be
      constructed in order to explore if, when the disease became more severe, a
      transition from a quasi ordered graph to a nearly completely random graph occurs.
      Plausibly, there exists a wide region where the graph has the properties of a
      "small-world". This kind of analyses could be potentially carried out using data
      coming from the spontaneous speech of schizophrenic patients, and can help to
      evaluate the progress of the disease. At the same time, these geometrical
      representations could help to evaluate the effect of treatments.

PMID- 16996228
TI  - Adherence behaviour with psychotropic medication is a form of self-medication.
AB  - Adherence with psychotropic medication is at least at poor as adherence with
      medication for physical health problems. There has been an assumption this was
      due to loss of insight resulting from psychiatric disorders themselves.
      Consequently, interventions have focussed on treating the underlying psychiatric
      disorder and generating psychological strategies to promote awareness. Recent
      surveys of patient preferences for information and involvement in health care
      decisions highlight that most individuals want to participate in the process of
      medical care. Patients often have strong pre-existing beliefs about different
      therapeutic options. This is supported by the self-determination theory which
      distinguishes between autonomous behaviour and behaviours that are influenced by
      external forces. When considering the patient perspective in medication
      adherence, it is useful to consider the self-medication hypothesis. This can
      equally be applied to prescribed and non-prescribed drugs. The self-medication
      hypothesis states that patients decide to start, adjust or stop prescribed
      medication according to perceived health needs. Such decisions are often
      conducted intentionally and rationally, given the information available to the
      patient and their understanding of their condition. In this narrative review, the
      evidence for and against intentionality in psychotropic adherence behaviour is
      examined. Studies of compliance and related predictors are examined in
      depression, schizophrenia and bipolar affective disorder. Results suggest that
      although concordance depends on patient, illness and clinician factors, patient
      choice is usually the final common pathway. Illness severity and insight is
      important in some cases but can act in concert with cognitive factors.
      Individuals appear to prefer to take medication "as required" (symptomatically)
      rather than prophylactically. Significant influences upon self-medication habits
      are prior health beliefs, medication attitudes, adverse effects and adequacy of
      communication from the health care professional. The self-medication hypothesis
      applied to prescribed psychotropic medication should assist rather than heed
      clinicians in improving adherence by taking a patient centred approach and where
      possible promoting patient autonomy.

PMID- 16996229
TI  - Malnutrition causes a reduction in alveolar epithelial sodium and chloride
      transport which predisposes to death from lung injury.
AB  - BACKGROUND: All forms of malnutrition have been associated with increased
      severity of pneumonia, an increased pneumonia associated mortality and an
      increased risk of pulmonary fluid overload. Malnutrition was found to be
      associated with increased sweat sodium and chloride concentrations. A reduction
      of systemic sodium and chloride transport reflected in sweat sodium and chloride
      levels has been linked to increased severity of pulmonary edema in children with
      septicemia. HYPOTHESIS: Malnutrition causes a reduction in alveolar epithelial
      sodium and chloride transport which predisposes to death from lung injury.
      SUPPORTING EVIDENCE FOR THE HYPOTHESIS: Malnutrition caused reduced pulmonary
      fluid clearance in the rat model. Amiloride insensitive pulmonary fluid clearance
      in malnourished rats was reduced. The reduction in fluid clearance was reversible
      by beta agonists which increases epithelial sodium and chloride transport.
      IMPLICATIONS OF THE HYPOTHESIS: Reduction of alveolar ion and fluid transport
      capacity explains the predisposition to death from pulmonary edema associated
      with intravenous fluids and blood transfusions in inpatients with malnutrition.
      Reduced alveolar epithelial ion transport impairs absorption of intra-alveolar
      inflammatory exudate in pneumonia leading to a increased severity of respiratory
      compromise and increased mortality. MEANS TO TEST THE HYPOTHESIS: Nasal potential
      difference measurements could compare airway epithelial sodium and chloride
      transport in patients with and without malnutrition and malnutrition associated
      lung disease. Sweat sodium and chloride concentrations could be compared in
      patients with and without respiratory disease associated with malnutrition and
      correlated with the severity of respiratory compromise.

PMID- 16996231
TI  - Alcohol expectancies, drinking refusal self-efficacy and drinking behaviour in
      Asian and Australian students.
AB  - The effects of alcohol expectancies (AE) and drinking refusal self-efficacy
      (DRSE) in predicting alcohol consumption in Caucasians has been well studied.
      However, the role of AE and DRSE in Asian students is still not well understood.
      This study reported on this using Caucasian (n=98) and Asian (n=92) student
      samples. Participants completed the Alcohol Use Disorder Identification Test
      (AUDIT) to measure their hazardous alcohol consumption, and the drinking
      expectancy profile (DEP) to assess their alcohol related expectancies and ability
      to resist drinking in certain situations. Results showed that Caucasians reported
      significantly higher confidence, higher sexual interest, and higher tension
      reduction expectancies than Asians. Conversely, Asians significantly expected
      cognitive enhancement and negative consequences more than Caucasians. Relative to
      Caucasians, the Asian sample also reported that they would be more able to refuse
      alcohol when under social pressure. Results from regression analyses showed that
      for the Caucasian sample, AE, DRSE and their interactions were significant
      predictors of alcohol consumption. For the Asian group, the only significant
      effect to emerge was that DRSE was negatively related to alcohol consumption. The
      clinical implications of the differential pattern of results between the samples
      are discussed in terms of self-efficacy and negative consequences of alcohol
      consumption, especially when dealing with university aged individuals.

PMID- 16996230
TI  - Smokeless tobacco brand switching: a means to reduce toxicant exposure?
AB  - The purpose of this study was to examine the effects of smokeless tobacco (ST)
      brand switching on biomarkers of ST exposure and on ST use. Subjects seeking
      treatment to reduce their use were randomized to ST brand switching with
      controlled ST topography, brand switching with ad libitum ST use, or a waitlist
      control with subsequent randomization to one of these two conditions. The
      waitlist control group was included to assess whether changes were a consequence
      of time effect. During the intervention, Copenhagen or Kodiak ST users were asked
      to switch to products that were sequentially lower in nicotine content: Skoal
      Long Cut Straight or Wintergreen for 4 weeks and then Skoal Bandits for the
      subsequent 4 weeks. Measures were obtained during the course of treatment and at
      12-week follow-up. Significant reductions in total urinary cotinine and 4
      (methylnitrosamino)-L-(3-pyridyl)-L-butanol (NNAL) plus its glucuronides (total
      NNAL) were observed with no significant differences between the controlled
      topography and ad libitum conditions. Significant reductions were also observed
      in the amount and duration of dips with a significant intervention effect for
      durational measures. At 12 weeks, the 7-day biochemically-verified tobacco
      abstinent rate was 26% in the ad libitum group. ST brand switching may be a
      feasible alternative intervention for ST users interested in quitting but
      unwilling to stop ST use completely.

PMID- 16996232
TI  - Women-only and mixed-gender drug abuse treatment programs: service needs,
      utilization and outcomes.
AB  - OBJECTIVES: This prospective longitudinal study examined service needs,
      utilization and outcomes for 189 women in women-only (WO) programs and 871 women
      in mixed-gender (MG) programs. METHODS: The Addiction Severity Index was
      administered at both intake and the 9-month follow-up interview to assess
      clients' problem severity and outcomes, and the Treatment Service Review was
      given at the 3-month interview to measure service utilization. Treatment
      completion and arrests were based on official records. RESULTS: Compared to women
      in MG programs, women in WO programs were more likely to be White, less educated,
      physically abused in the past 30 days and in residential treatment (as opposed to
      outpatient treatment). Women in WO programs also had greater problem severity in
      a number of domains including alcohol, drug, family, medical and psychiatric.
      They utilized more treatment services and had better drug and legal outcomes at
      follow-up compared to women in MG programs. Program type was not predictive of
      treatment retention/completion or outcomes in other domains (i.e., alcohol,
      employment, family, medical and psychiatric). CONCLUSIONS: The greater problem
      severity of women treated in WO programs and their better drug and legal outcomes
      suggest that these specialized services are filling an important gap in addiction
      services.

PMID- 16996233
TI  - Prevalence of equine herpesvirus type 2 (EHV-2) DNA in ocular swabs and its cell
      tropism in equine conjunctiva.
AB  - Equine herpes virus 2 (EHV-2), a gamma(2)-herpesvirus, is common in horses of all
      ages. Its role as a primary pathogen is unclear but there is an association
      between EHV-2, respiratory disease and keratoconjunctivitis. The purpose of this
      study was to gain more information on the prevalence of EHV-2 DNA in conjunctival
      swabs from horses with and without ocular disease and to define the anatomical
      site and cell type harbouring viral genome or antigen. By polymerase chain
      reaction (PCR) 22 out of 77 (28.6%) ocular swabs of clinically healthy and only 4
      out of 48 (8.3%) samples from diseased horses were positive. To define the main
      virus reservoir ocular tissue from 13 randomly selected horses without
      pathological evidence of ocular disease were analysed by nested PCR. In two
      horses optic nerve, lacrimal gland and conjunctiva, in further two cases lacrimal
      gland and conjunctiva and in four horses the conjunctiva only were EHV-2 PCR
      positive. For specifying the target cell we focused on conjunctivae and selected
      3 out of 15 clinically healthy slaughterhouse horses positive for EHV-2 by PCR.
      In situ hybridisation on sections of these paraffin embedded conjunctivae
      localized viral genome in histiocyte-like cells of the submucosa.
      Immunohistochemical staining with an EHV-2 or S100 specific polyclonal antiserum
      demonstrated that Langerhans cells were co-localized in the same region of the
      sample section where virus positive cells were detected. Furthermore, we
      concluded that detection of viral antigen revealed a productive virus infection.

PMID- 16996234
TI  - Determination of interleukin-1alpha in human NCTC 2544 keratinocyte cells as a
      predictor of skin irritation from lysine-based surfactants.
AB  - Lysine derivative surfactants are a class of amino acid-based surfactants
      synthesized as lecithin analogues that deserve particular attention because of
      their low toxicity and high biocompatibility. To complete the toxicological
      profile of these surfactants, IL-1 alpha production (cell-associated and release
      to the culture medium) was determined as an in vitro method for predicting skin
      irritation. In addition, an MTT assay was used as a viability marker in
      keratinocytes NCTC 2544. Keratinocytes are a biologically relevant target for
      developing in vitro techniques to assess skin irritants: moreover, they are the
      principal source of the proinflammatory cytokine IL-1 alpha in the epidermis.
      Lysine derivatives proved to be less potent in stimulating IL-1 alpha synthesis
      and induced a lower release of this cytokine into the culture medium when
      compared to the anionic surfactant sodium dodecyl sulfate. Due to their low
      irritancy potential, lysine-based surfactants may offer promising applications in
      pharmaceutical and cosmetic preparations.

PMID- 16996235
TI  - Effects of nimodipine, an L-type calcium channel antagonist, on the chicken's
      cochlear potentials.
AB  - At most synapses in the brain, neurotransmitter release depends on N-type or P/Q
      type calcium channels. However, available in vitro experimental data suggest that
      there exist almost exclusively L-type calcium channels in sensory hair cells of
      most species. To test whether chicken hair cells depend on L-type calcium
      channels for neurotransmitter release, we examined the effects of nimodipine, a
      selective L-type calcium channel antagonist, on acoustically evoked cochlear
      potentials in 10-15 week old chickens in vivo. Diffusion of nimodipine into scala
      tympani significantly elevated threshold, dramatically decreased the amplitude
      and increased the latency of the compound action potential within 20 min of drug
      application. The summating potential was also significantly reduced in amplitude,
      but the cochlear microphonic was relatively less affected. All the effects were
      reversible after nimodipine was washed out with artificial perilymph except that
      the cochlear microphonic amplitude remained decreased. Application of omega
      conotoxin GVIA, an N-type calcium channel antagonist and agatoxin Tk, a P-type
      calcium channel antagonist had no observable effects on the cochlear potentials.
      These results suggest that L-type calcium channels control neurotransmitter
      release from avian hair cells.

PMID- 16996236
TI  - Development of a semi-automated chemical stability system to analyze solution
      based formulations in support of discovery candidate selection.
AB  - A semi-automated chemical stability system was developed, validated, and
      implemented to assess the chemical and physical stability (24 h) of intravenous
      and oral solution based formulations in support of preliminary in vivo drug
      discovery studies. The system utilizes a single Agilent 1100 LC and Xterra column
      with multiple UV wavelength monitoring. Mobile phase selection, either basic or
      acidic, is selected base upon on the physico-chemical properties of the test
      compound. The system was validated against 14 new chemical entities across
      multiple therapeutic areas. The results indicated that drug discovery compounds
      could be accurately quantified (<2% R.S.D.) in a wide range of formulation
      vehicles in greater than 90% of the test cases. This method can be used as a
      quantitative tool for triaging formulation variables and packaging configurations
      to quickly develop stable solutions for dosing.

PMID- 16996237
TI  - Lymphatic mapping and sentinel node harvesting in patients with recurrent breast
      cancer.
AB  - AIMS: To evaluate the feasibility and consequences of lymphatic mapping and a
      ("repeat") sentinel lymph node (SLN) procedure in patients with breast cancer
      relapse after previous breast and axillary surgery. METHODS: Review and
      presentation of a patient cohort. All SLN procedures included lymphoscintigraphy
      and blue dye injection technique. RESULTS: Twelve cases are described: two
      patients after a previous SLN procedure and ten after a previous complete
      axillary lymph node dissection (ALND). Ten patients (83%) had a successful repeat
      SLN biopsy. After previous ALND, lymphoscintigraphy revealed drainage towards the
      internal mammary chain in three patients, and contralateral axillary drainage in
      four. Based on the information from the "repeat" SLN biopsy further treatment
      strategy was altered in seven of the 12 patients. CONCLUSION: Lymphatic mapping
      and (repeat) SLN biopsy is possible and can be informative in patients who
      present with a relapse of breast cancer after previous surgery for primary breast
      cancer.

PMID- 16996238
TI  - Yolk sac tumours of the ovary: an update.
AB  - AIMS: Yolk sac tumours of the ovary (YST), also called endodermal sinus tumours
      (EST) are rare and highly malignant tumours of utmost importance occurring in
      children and young adults. In the past, outcome was very poor and the disease was
      almost always fatal. With the refinement of chemotherapeutic regimens in the last
      several decades, survival rates have improved dramatically and fertility
      preserving surgery has become possible. The aim of this review is to provide the
      reader with an analysis of the available literature and a rational approach to
      patient management. METHODS: We performed a literature search in the PubMed
      database and the reference lists of relevant articles concerning yolk sac tumours
      of the ovary. FINDINGS AND CONCLUSION: There are no randomised studies relating
      to the management of YST of the ovary. The available literature is composed of
      retrospective reviews and case reports that span several decades. Prognosis
      nowadays is good in stage I and II but still comparable to that of ovarian
      epithelial cancer in stage III and IV. The overall good prognosis is due to the
      fact that most of ovarian YST are diagnosed at an early stage where 5years
      survival reaches 95%. Appropriate surgical treatment for patients where fertility
      needs to be preserved consists in laparotomy with unilateral salpingo
      oophorectomy, peritoneal cytologic studies, omentectomy, multiple peritoneal and
      abdominal biopsies and resection of all visible disease. Three courses of BEP
      (bleomycin, etoposide, cisplatin) is the current standard therapy and four
      courses is recommended in case of bulky residual disease after surgery. Serum
      alpha-feto-protein (AFP) is a useful marker for the diagnosis and management of
      YST.

PMID- 16996239
TI  - Age as predictor in patients with cutaneous melanoma submitted to sentinel lymph
      node biopsy.
AB  - AIMS: To analyse the age as prognostic factor exploring the melanoma database at
      the National Cancer Institute in Naples. METHODS: Three hundred and ninety-nine
      patients with cutaneous melanoma were treated with sentinel lymph node biopsy
      from 1996 to 2003 at the National Cancer Institute of Naples. The results were
      analysed with particular attention to the overall survival among patients younger
      or older than 50 years of age. RESULTS: No differences were recorded between the
      younger and older group in terms of the identification rate and incidence of
      metastases. The analyses of disease-free survival and overall survival showed a
      significantly more favourable outcome in younger patients. The 5-year overall
      survival and the 5-year disease free survival were 81.8% vs. 68.0% and 76.3% vs.
      59.1% for the younger and older group, respectively. CONCLUSIONS: The results
      suggest that in the management of cutaneous melanoma, age might be considered as
      prognostic factor both for disease free survival and overall survival.

PMID- 16996240
TI  - Stimulated production of interleukin-8 covaries with psychosocial risk factors
      for inflammatory disease among middle-aged community volunteers.
AB  - A growing literature suggests that psychosocial factors, such as chronic stress
      and depression, are associated with increased vulnerability to inflammatory
      disease; however, the mechanisms of this effect remain unclear. One possibility
      is that these psychosocial characteristics are associated with activation of
      innate inflammatory pathways. Here, we explore relationships between a range of
      psychosocial risk factors for inflammatory disease and a measure of inflammatory
      potential, lipopolysaccharide-induced production of the monocyte-derived
      proinflammatory cytokines/chemokines interleukin (IL)-1beta, IL-6, TNF-alpha, and
      IL-8 among a community sample of 183 healthy adults aged 30-54 years. After
      controlling for demographic factors, health behavior practices, blood pressure,
      and white blood cell count, hierarchical regression analyses revealed a positive
      relationship between production of IL-8 and symptoms of depression, trait
      negative affect, and perceived stress. In contrast, there was an inverse
      relationship between IL-8 production and perceived social support. Relationships
      between IL-8 and symptoms of depression and perceived stress were attributable
      primarily to dispositional differences in NA. The relationship between negative
      affect measures and IL-8 was independent of social support. Although there were
      significant univariate associations between higher IL-6 production and symptoms
      of depression and less social support, these relationships did not withstand
      adjustment for demographic controls. There were no significant associations
      between IL-1beta or TNF-alpha and any of the psychosocial parameters. Our
      findings suggest that individuals at greater psychosocial risk for the
      development of inflammatory diseases, including cardiovascular disease, also show
      greater stimulated production of the proinflammatory chemokine, IL-8. Further
      exploration of this potential psychophysiological pathway is warranted.

PMID- 16996241
TI  - A putative role for cytokines in the impaired appetite in depression.
AB  - Impaired appetite and weight changes are commonly seen in patients with
      depression, but the pathophysiology behind this imbalance between energy intake
      and energy expenditure remains largely unknown. The aim of this paper is to
      review the literature regarding a possible role for cytokines in the regulation
      of appetite and body weight, with special emphasis on depression. There now
      exists a substantial amount of evidence that depressed patients show signs of
      immune activation including increased levels of proinflammatory cytokines.
      Cytokines, which by themselves have anorectic properties, stimulate the release
      of the cytokine-like anorexogenic peptide leptin. In addition to their anorectic
      properties, both proinflammatory cytokines and leptin interact with the
      hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS)
      and the immune system. In turn, these systems regulate energy balance as well as
      they are dysfunctional in depression. Furthermore, both proinflammatory cytokines
      and leptin can induce anhedonia, one of the cardinal symptoms of depression. In
      view of the different effects on appetite and/or body weight observed in
      melancholic versus atypical depression, we suggest that cytokines are
      differentially altered in these subtypes of depression, and that this may explain
      some of the inconsistency in the reported findings of cytokine as well as leptin
      levels in depressed patients. Finally, we propose that the immune system uses the
      interoceptive pathway projecting to the insular cortex, a brain region where
      cytokine-induced changes in appetite could be partly mediated, and that this
      pathway is activated in depression.

PMID- 16996242
TI  - Depressive symptoms and production of proinflammatory cytokines by peripheral
      blood mononuclear cells stimulated in vitro.
AB  - One potential pathway by which depression may impact health is through modulation
      of immune function. Depressed individuals have been shown to display reductions
      in measures of cellular immune competence as well as elevated markers of systemic
      inflammation. The current study assessed the in vitro production of
      proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha by peripheral blood
      mononuclear cells (PBMCs) in response to mitogen stimulation within a community
      based sample of 79 midlife women. Results indicate that midlife women with higher
      levels of depressive symptoms (as assessed with the Center for Epidemiologic
      Studies Depression scale) and greater body mass index (BMI) displayed diminished
      production of IL-6, IL-1beta, and TNF-alpha by stimulated PBMCs, as compared with
      their less-depressed counterparts. These relationships remained after controlling
      for such health-related variables as age, recent sleep disruption, physical
      activity level, and self-reported medical history. In contrast, depressive
      symptoms were not significantly associated with circulating levels of the same
      proinflammatory cytokines (IL-6, IL-1beta, and TNF-alpha) obtained from serum
      samples available for a subset of 62 of the study participants. Moreover,
      circulating proinflammatory cytokine levels were not significantly associated
      with the in vitro proinflammatory cytokine production outcomes. Further research
      is needed to clarify the clinical significance of the current study findings, and
      the extent to which in vitro tests of stimulated proinflammatory cytokine
      production are associated with other measures of cellular immune function and/or
      circulating markers of systemic inflammation obtained across various study
      populations.

PMID- 16996243
TI  - In vitro exposure to environmental tobacco smoke induces CYP1B1 expression in
      human luteinized granulosa cells.
AB  - Women smokers and women exposed to environmental tobacco smoke (ETS) have reduced
      ovarian function as evidenced by an earlier menopause, reduced follicular
      numbers, decreased levels of circulating estradiol, and decreased conception
      rates; however, the mechanism of action of altered ovarian function by ETS is
      poorly understood. The direct effects of ETS were evaluated using human
      luteinized granulosa cells (HLGCs) exposed to ETS in primary cell culture.
      Exposure to ETS caused a decrease in both estradiol and progesterone production.
      There was a concentration dependent increase in CYP1B1 gene and protein
      expression without a change in catechol-O-methyltransferase (COMT) expression.
      This is the first report of CYP1B1 induction secondary to ETS exposure in cells
      from the human ovary. CYP1B1 metabolizes both endogenous estrogens and
      polyaromatic hydrocarbons in ETS to a variety of reactive species and may
      contribute to the complex effects of ETS on ovarian function.

PMID- 16996244
TI  - Developmental toxic effects of chronic exposure to high doses of iodine in the
      mouse.
AB  - Chronic exposure to high doses of iodine induces thyroid dysfunction, but effects
      of chronic exposure to high amounts of iodine on pregnancy and fetal outcome are
      uncertain. In the present study, Balb/C mice were given different doses of iodine
      at the levels of 0 (sterile water), 1,500, 3,000, 6,000, 12,000 and 24,000 micro
      g/L in drinking water for 4 months, then were mated and the developmental
      toxicity and teratogenicity were evaluated. An obvious colloid goiter was
      observed, and serum total thyroxine (TT4) levels increased and serum total
      triiodothyronine (TT3) levels decreased significantly in dams when iodine dose
      reached 3,000 micro g/L. Maternal effect was evident by the reduction of average
      daily food consumption in higher doses of iodine groups. Embryotoxicity and
      teratogenicity were mainly indicated by the reduced body weight in female
      fetuses, the decreased number of live fetuses, and the increased incidence of
      resorptions, and especially skeletal variations. These results suggest that
      exposure to maternally toxic doses of iodine may have a potential developmental
      toxic effect.

PMID- 16996245
TI  - The outcome of pregnancy following pre-pregnancy or early pregnancy alendronate
      treatment.
AB  - In spite of a substantial increase in the use of bisphosphonates at child bearing
      age, very little is known regarding its use in pregnancy. We describe the outcome
      of 24 pregnancies after pre-pregnancy or early pregnancy alendronate therapy.
      Based on the pregnancy outcome it seems that alendronate does not impose a major
      teratogenic risk.

PMID- 16996246
TI  - Vaccination against nicotine does not prevent nicotine-induced changes in fetal
      nicotinic receptor binding and c-fos mRNA expression in rats.
AB  - Gestational exposure of rats to nicotine produces long-lasting alterations in
      brain development. Vaccination of adult female rats against nicotine reduces the
      distribution of maternally administered nicotine to fetal brain, suggesting that
      vaccination might protect against these effects. In the current study, the
      effects of vaccination on nicotine-induced changes in fetal (3)H-epibatidine
      binding and c-fos mRNA expression were evaluated using tissue from a previous
      pharmacokinetic study of vaccination. An intermittent nicotine dosing regimen
      designed to resemble nicotine intake in a smoker was administered from GD1-20.
      Peak nicotine levels in fetal brain were reduced by vaccination, whereas the
      chronic accumulation of nicotine in fetal brain was not. Gestational nicotine
      exposure produced significant increases in (125)I-epibatidine binding to brain
      and spinal cord on GD20, and decreased c-fos mRNA expression in fetal striatum,
      adrenal and lung. Vaccination did not significantly alter these effects. These
      data suggest that nicotine dosing, using a clinically relevant intermittent bolus
      dose regimen, produces substantial changes in fetal nicotinic receptor and c-fos
      mRNA expression. The decrease in c-fos mRNA expression contrasts with previously
      reported increases, and suggests that the nicotine dosing regimen used may
      influence its effects. The lack of effect of vaccination suggests that the
      cumulative exposure of fetal tissues to nicotine may influence the measured
      parameters to a greater extent than peak exposure levels.

PMID- 16996247
TI  - Magnetic resonance and spectroscopic imaging in prenatal alcohol-exposed
      children: preliminary findings in the caudate nucleus.
AB  - Magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging
      (MRSI) offer unique, noninvasive methods of measuring, respectively, in vivo
      quantitative neuroanatomy and neurochemistry. The main purpose of the present
      study was to identify and compare the neuroanatomical and neurochemical
      abnormalities that are associated with prenatal exposure to alcohol in both fetal
      alcohol syndrome (FAS)-diagnosed children and those diagnosed with fetal alcohol
      effects (FAE). MR data of three age-, gender- and race-balanced groups of
      children, FAS-diagnosed, FAE-diagnosed and non-exposed controls, were compared.
      Effects of prenatal alcohol exposure, regardless of diagnosis, were found in the
      caudate nucleus. Specifically, a significantly smaller caudate nucleus was found
      for the FAS and FAE participants compared to the controls. In addition, the
      metabolite ratio of N-acetyl-aspartate to creatine (NAA/Cr), an indicator of
      neuronal function, in left caudate nucleus of both the FAS and FAE participants
      was elevated compared to the control group. Analysis of absolute concentrations
      revealed that the increase in the ratio of NAA/Cr was due to an increase in NAA
      alone. Although its exact function in the CNS is unknown, NAA is believed to be a
      neuronal marker due to its exclusive localization to neurons. Some also speculate
      a role for NAA in myelination. Elevated NAA in the prenatal alcohol-exposed
      participants could indicate a lack of normal program cell death, dendritic
      pruning and/or myelination during development. The present study demonstrates
      that prenatal alcohol-exposed children, with or without facial dysmorphology,
      have abnormal brain anatomy and chemistry.

PMID- 16996248
TI  - FOXP3 polymorphisms in type 1 diabetes and coeliac disease.
AB  - The FOXP3 gene encodes a transcription factor thought to be essential for the
      development and function of T regulatory cells. Two previous studies have tested
      common polymorphisms in FOXP3 for association with type 1 diabetes (T1D) with
      conflicting results. The aim of our study was to see whether there is any
      evidence of association between the FOXP3 polymorphisms previously reported to be
      associated with T1D, in a Caucasian population regarding T1D and coeliac disease
      (CD). We further looked for evidence of interaction between FOXP3 polymorphisms
      and HLA-DR3 in conferring susceptibility to T1D. Initially, we analysed two
      microsatellites in the FOXP3 gene in 363 T1D nuclear families. Our results
      indicated an association between FOXP3 and T1D (global p=0.004) and a possible
      interaction between FOXP3 and the HLA-DR3-DQ2 susceptibility haplotype. We then
      genotyped an additional independent set of 826 T1D patients and 1459 controls as
      well as one CD dataset consisting of 325 families. A similar tendency was
      revealed in the CD family material (pnc=0.055 for the associated allele). On the
      other hand, we were unable to reproduce our initial findings in the T1D case
      control dataset (global p=0.6). Our results suggest that the tested FOXP3 markers
      do not have any major impact on susceptibility for these diseases.

PMID- 16996249
TI  - Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine
      production in macrophages via PKA- and NF-kappaB-independent mechanisms.
AB  - Activation of the beta(2) adrenergic receptor (beta(2)AR) located on macrophages
      has been reported to possess anti-inflammatory properties, inhibiting nuclear
      factor kappaB (NF-kappaB) activation and cytokine production induced by pro
      inflammatory stimuli. Here, we show that activation of the beta(2)AR in the
      absence of pro-inflammatory stimuli produced up to an 80- and 8-fold increase in
      IL-1beta and IL-6 transcripts, respectively, in the RAW 264.7 murine macrophage
      cell line. This increase in mRNA expression was accompanied by a significant
      increase in IL-1beta and IL-6 protein production. Pre-treatment of RAW cells with
      pharmacological inhibitors of protein kinase A (PKA) or NF-kappaB pathway failed
      to block this cytokine increase. Instead, the beta(2)AR-mediated increase in
      cytokines required activation of both the B-raf-ERK1/2 and p38 pathways.
      Treatment of RAW cells with the exchange protein directly activated by cAMP
      (EPAC) agonist also resulted in the up-regulation of IL-1beta and IL-6
      transcripts. Examination of the main transcription factors downstream of the
      ERK1/2 and p38 signaling revealed that beta(2)AR activation resulted in the
      stimulation of CRE-, but not C/EBPbeta-, ETS-, or NF-kappaB-dependent
      transcription. Western blot analysis further showed that among the transcription
      factors which recognize the CRE-binding site, ATF-1 and ATF-2 but not CREB
      proteins were phosphorylated in an ERK1/2- and p38-dependent manner.
      Collectively, these results demonstrate that beta(2)ARs possess pro-inflammatory
      properties and that their activation leads to IL-1beta and IL-6 production
      through ERK1/2- and p38-dependent activation of ATF-1 and ATF-2 transcription
      factors.

PMID- 16996250
TI  - Body weight and self-esteem in patients with schizophrenia evaluated with B-WISE.
AB  - BACKGROUND: Metabolic abnormalities and weight gain are an important problem in
      patients with schizophrenia. An instrument to evaluate body image and self-esteem
      related to weight has recently been developed (B-WISE). The first objective was
      to evaluate whether the findings of the original validation study could be
      confirmed in a European sample. The second objective was to explore the
      association of B-WISE scores with the metabolic syndrome and glucose
      abnormalities. METHODS: A Dutch translation of B-WISE was tested in a large
      sample of patients with schizophrenia (n=300) who underwent an extensive
      metabolic screening. RESULTS: The original findings with B-WISE were confirmed in
      an independent sample. Scores on B-WISE differed significantly as a function of
      BMI. Scores on B-WISE also differentiated patients with and without the metabolic
      syndrome and glucose abnormalities. Patients experiencing a recent weight gain
      had lower self-esteem and poorer psychosocial adaptation. CONCLUSION: B-WISE
      could be a useful instrument to evaluate the subjective psychosocial consequences
      associated with current weight and weight gain in patients with schizophrenia.

PMID- 16996251
TI  - Epiregulin, a member of the EGF family, is over-expressed in psoriatic epidermis.

PMID- 16996252
TI  - Enzyme-encapsulated silica monolayers for rapid functionalization of a gold
      surface.
AB  - We report a simple and rapid method for the deposition of amorphous silica onto a
      gold surface. The method is based on the ability of lysozyme to mediate the
      formation of silica nanoparticles. A monolayer of lysozyme is deposited via non
      specific binding to gold. The lysozyme then mediates the self-assembled formation
      of a silica monolayer. The silica formation described herein occurs on a surface
      plasmon resonance (SPR) gold surface and is characterized by SPR spectroscopy.
      The silica layer significantly increases the surface area compared to the gold
      substrate and is directly compatible with a detection system. The maximum surface
      concentration of lysozyme was found to be a monolayer of 2.6 ng/mm(2) which
      allowed the deposition of a silica layer of a further 2 ng/mm(2). For additional
      surface functionalization, the silica was also demonstrated to be a suitable
      matrix for immobilization of biomolecules. The encapsulation of organophosphate
      hydrolase (OPH) was demonstrated as a model system. The silica forms at ambient
      conditions in a reaction that allows the encapsulation of enzymes directly during
      silica formation. OPH was successfully encapsulated within the silica particles
      and a detection limit for the substrate, paraoxon, using the surface-encapsulated
      enzyme was found to be 20 microM.

PMID- 16996253
TI  - [Unilateral tonsillar enlargement in children: thinking about lymphoma].

PMID- 16996254
TI  - Maintenance of vascular endothelial growth factor and potentially other
      therapeutic proteins bioactivity during a photo-initiated free radical cross
      linking reaction forming biodegradable elastomers.
AB  - Previously, we prepared a biodegradable elastomeric device that can release
      different therapeutic proteins at a nearly constant rate in nanomolar
      concentrations with high bioactivity. The elastomer device was fabricated using a
      photo-initiated free radical cross-linking reaction of acrylated star(epsilon
      caprolactone-co-D,L-lactide) in organic solvent in the presence of solid protein
      particles. The objective of this study was to examine the effect of various
      parameters used for fabricating the photo-cross-linked elastomeric device on the
      stability of a therapeutic protein, vascular endothelial growth factor (VEGF), to
      determine which factor plays the dominant role in protecting VEGF. VEGF was
      lyophilized with or without bovine serum albumin (BSA) and then suspended in
      solid state in a macromer (acrylated star-poly(epsilon-caprolactone-co-D,L
      lactide)) solution containing different concentrations of a free radical
      initiator, 2,2-dimethoxy-2-phenylacetophenone (DMPA). The protein suspension was
      then UV-irradiated at different intensities. UV irradiation with the generation
      of free radicals was detrimental to VEGF stability. BSA preserved the VEGF
      bioactivity during UV irradiation but provided little protection in the presence
      of the photo-initiator DMPA. The acrylated macromer acted as a free radical
      scavenger and effectively preserved VEGF and BSA stability during UV-initiated
      photo-polymerization. The detrimental effect of UV radiation with free radical
      generation on VEGF stability during device manufacture can be eliminated by
      choosing the proper bulking agents coupled with an efficient photo-polymerization
      reaction.

PMID- 16996256
TI  - Rapid direct determination using combined separation by prepared immunomagnetic
      and flow cytometry of Flavobacterium psychrophilum.
AB  - Flavobacterium psychrophilum, the causative agent of bacterial cold-water disease
      (BCWD), was originally isolated from coho salmon Oncorhychus kisutch in the USA.
      Bacterial cold-water disease has since been spreading throughout Japan and has
      caused serious damage to populations of ayu Plecoglossus altivel in many farms
      and rivers. The rapid method of detecting for F. psuchrophilum is requested,
      however, traditional methods are laborious because of complicated assay
      procedures. In this study, a rapid method of detecting F. psychrophilum was
      developed using a modified method of flow cytometry (FCM) analysis and
      immunomagnetic separation (IMS). Magnetic iron, in small particles, was prepared
      by the reaction of a mixture of ferric and ferrous ions under alkaline
      conditions. The particles were coated with antiserum against F. psychrophilum by
      dextran. Polyclonal antibodies (anti-F. psychrophilum) conjugated with
      fluorescein isothiocyanate (FITC) were reacted with F. psychrophilum, and then
      prepared immunomagnetic were applied using IMS, followed by FCM determination. A
      good correlation was observed between the cell numbers determined by the FCM
      method and the traditional method in the range of 10(2)-10(8) cells ml(-1). The
      FCM analysis could count cells within 1min, and the total analysis time,
      including sample preparation, was less than 2 h.

PMID- 16996255
TI  - Release characteristics of diclofenac sodium from poly(vinyl alcohol)/sodium
      alginate and poly(vinyl alcohol)-grafted-poly(acrylamide)/sodium alginate blend
      beads.
AB  - In this study, acrylamide (AAm) was grafted onto poly(vinyl alcohol) (PVA) with
      UV radiation at ambient temperature. The graft copolymer (PVA-g-PAAm) was
      characterized by using Fourier transform infrared spectroscopy (FTIR), elemental
      analysis and differential scanning calorimetry (DSC). Polymeric blend beads of
      PVA-g-PAAm and PVA with sodium alginate (NaAlg) were prepared by cross-linking
      with glutaraldehyde (GA) and used to deliver a model anti-inflammatory drug,
      diclofenac sodium (DS). Preparation condition of the beads was optimized by
      considering the percentage entrapment efficiency, particle size, swelling
      capacity of beads and their release data. Effects of variables such as PVA/NaAlg
      ratio, acrylamide content, exposure time to GA and drug/polymer ratio on the
      release of DS were discussed at three different pH values (1.2, 6.8, 7.4). It was
      observed that, DS release from the beads decreased with increasing PVA/NaAlg
      (m/m) ratio, drug/polymer ratio (d/p) and extent of cross-linking. However, DS
      release increased with increasing acrylamide content of the PVA-g-PAAm polymer.
      The highest DS release was obtained to be 92% for 1/1 PVA-g-PAAm/NaAlg ratio
      beads. It was also observed from release results that DS release from the beads
      through the external medium is much higher at high pH (6.8 and 7.4) than that at
      low pH (1.2). The drug release from the beads mostly followed Case II transport.

PMID- 16996257
TI  - Direct electrochemistry and electrocatalysis of horseradish peroxidase
      immobilized in sol-gel-derived ceramic-carbon nanotube nanocomposite film.
AB  - The sol-gel-derived ceramic-carbon nanotube (SGCCN) nanocomposite film fabricated
      by doping multiwall carbon nanotubes (MWNTs) into a silicate gel matrix was used
      to immobilize protein. The SGCCN film can provide a favorable microenvironment
      for horseradish peroxidase (HRP) to perform direct electron transfer (DET) at
      glassy carbon electrode. The HRP immobilized in the SGCCN film shows a pair of
      well-defined redox waves and retains its bioelectrocatalytic activity to the
      reduction of O2 and H2O2, which is superior to that immobilized in silica sol-gel
      film.

PMID- 16996258
TI  - Computational selection of nucleic acid biosensors via a slip structure model.
AB  - Aptamers have been shown to undergo ligand-dependent conformational changes, and
      can be joined to ribozymes to create allosteric ribozymes (aptazymes). An anti
      flavin (FMN) aptamer joined to the hammerhead ribozyme yielded an aptazyme that
      underwent small, FMN-dependent displacements in the helix that joined the aptamer
      and ribozyme. This 'slip structure' model in which alternative sets of base-pairs
      are formed in the absence and presence of ligand proved amenable to energetic and
      computational modeling. Initial successes in modeling the activities of known
      aptazymes led to the in silico selection of new ligand-dependent aptazymes from
      virtual pools that contained millions of members. Those aptazymes that were
      predicted to best fit the slip structure model were synthesized and assayed, and
      the best-designed aptazyme was activated 60-fold by FMN. The slip structure model
      proved to be generalizable, and could be applied with equal facility to
      computationally generate aptazymes that proved to be experimentally activated by
      other ligands (theophylline) or that contained other catalytic cores (hairpin
      ribozyme). Moreover, the slip structure model could be applied to the prediction
      of a ligand-dependent aptamer beacon biosensor in which the addition of the
      protein vascular endothelial growth factor (VegF) led to a 10-fold increase in
      fluorescent signal.

PMID- 16996259
TI  - Cancer incidence in first-degree relatives of a population-based set of cases of
      early-onset breast cancer.
AB  - Reliable determination of familial risks for cancer is important for clinical
      counselling, cancer prevention and understanding cancer aetiology. Family-based
      gene identification efforts may be targeted if the risks are well characterised
      and the mode of inheritance is identified. Early-onset breast cancer in a family
      member is a risk indicator for cancer among first-degree relatives; however, the
      familial risk pattern has not been assessed fully in population-based incidence
      studies. We estimated the risks for cancers of the breast, ovary and other sites
      among the first-degree relatives of 8868 patients in whom breast cancer was
      diagnosed before they reached the age of 50 years (diagnosed during the period
      1943-1999). Population registers and parish records were used to identify 31,235
      first-degree relatives, who were followed up to 31 December 2002 for occurrence
      of cancer by linkage to the Danish Cancer Registry. The observed incidence rates
      were compared with national rates adjusted for age, sex and calendar period.
      Overall, 39% of the 674 cases of breast cancer and 43% of the 143 cases of
      ovarian cancer among relatives were associated with a diagnosis of early-onset
      breast cancer in a family member. Among relatives under 50 years of age, the
      proportions were 56% and 58%, respectively, and among relatives 50 years or above
      the proportions were approximately 30% and 10%. In addition, a slightly but
      significantly increased risk for cancer of the cervix uteri was observed among
      relatives, and among those under 50 years of age, we found significantly
      increased risks for cancers of the colon and gall-bladder. In conclusion, the
      excess risk for breast cancer in first-degree relatives is large and remains
      sizable in the subgroup of female relatives aged 50 years or older, and that
      mutations in BRCA1/2 seem to explain only half of breast cancer cases
      attributable to family history.

PMID- 16996260
TI  - Better quality of life among 10-15 year survivors of Hodgkin's lymphoma compared
      to 5-9 year survivors: a population-based study.
AB  - This study describes the quality of life (QoL) of long-term Hodgkin's lymphoma
      survivors and compares it to an age-matched normative sample. The population
      based Eindhoven Cancer Registry was used to select all patients diagnosed with
      Hodgkin's lymphoma from 1989 to 1998. Eighty percent of survivors completed the
      SF-36 and the quality of life-cancer survivors questionnaire. QoL was better
      among patients diagnosed 10-15 years ago compared to patients diagnosed 5-9 years
      ago. The patients diagnosed 5-9 years ago experienced lower general health,
      social functioning, mental health and vitality compared to an age-matched
      normative sample, while the patients diagnosed 10-15 years earlier reported lower
      general health but better physical functioning. Most patients reported that their
      work situation did not change. Problems pertaining to the obtainment of health
      insurance, life insurance and mortgages were high. QoL among Hodgkin's lymphoma
      survivors is lower compared to an age-matched normative sample. Survivors
      furthermore experience some (financial) problems in the years after diagnosis.

PMID- 16996261
TI  - Expression analysis of stage III serous ovarian adenocarcinoma distinguishes a
      sub-group of survivors.
AB  - It is difficult to predict the clinical outcome for patients with ovarian cancer.
      However, the use of biomarkers as additional prognostic factors may improve the
      outcome for these patients. In order to find novel candidate biomarkers,
      differences in gene expressions were analysed in 54 stage III serous ovarian
      adenocarcinomas with oligonucleotide microarrays containing 27,000 unique probes.
      The microarray data was verified with quantitative real-time polymerase chain
      reaction for the genes TACC1, MUC5B and PRAME. Using hierarchical cluster
      analysis we detected a sub-group that included 60% of the survivors. The gene
      expressions in tumours from patients in this sub-group of survivors were compared
      with the remaining tumours, and 204 genes were found to be differently expressed.
      We conclude that the sub-group of survivors might represent patients with
      favourable tumour biology and sensitivity to treatment. A selection of the 204
      genes might be used as a predictive model to distinguish patients within and
      outside of this group. Alternative chemotherapy strategies could then be offered
      as first-line treatment, which may lead to improvements in the clinical outcome
      for these patients.

PMID- 16996262
TI  - Increasing oxidative damage and loss of mismatch repair enzymes during breast
      carcinogenesis.
AB  - This study examined the expression of oxidative damage markers 8
      hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE) and nitrotyrosine using
      immunohistochemical techniques. In addition, DNA topoisomerase II binding protein
      1 (TopBP1) and mismatch repair proteins 2 and 6 (MSH2 and MSH6) were
      immunostained in a series of 80 stage I invasive breast tumours, 26 in situ
      breast carcinomas and 12 benign breast hyperplasias. 8-OHdG, HNE and
      nitrotyrosine expression were considerably weaker in hyperplasias than in in situ
      lesions, which, in turn, showed less oxidative damage than T1N0 tumours.
      Hyperplasias and in situ tumours were all, at least moderately, positive for
      MSH2, and nearly all were positive for MSH6. Nitrotyrosine expression was
      associated with HNE (P<0.0005) and 8-OHdG (P=0.041) in the T1N0 cohort. To
      conclude, there is increasing oxidative stress during the early steps of breast
      carcinogenesis. On the other hand, a significant reduction in expression of
      mismatch repair proteins occurs during the progression of in situ lesions to
      invasive tumours.

PMID- 16996263
TI  - Kinetic modeling for the biosorption of copper by pretreated Aspergillus niger
      biomass.
AB  - In this present work, a kinetic model for biosorption of copper was developed
      considering the possibility of different forms of functional groups being present
      on the surface of the biomass prepared from Aspergillus niger. Results showed
      that metal uptake by A. niger was a mass transfer driven process, requiring only
      30min to achieve 70% adsorption efficiency. Copper sorption by A. niger was
      influenced by the biomass dose, initial metal ion concentration, and pH of the
      solution. The Langmuir and Freundlich adsorption isotherms were used to describe
      the behavior of the system at different pH. The retention capacity of the biomass
      was determined at pH 6.0 to be equal to 23.62mg/g of biomass. The pretreatment
      with formalin improved the uptake of metal ion.

PMID- 16996264
TI  - Feasibility of methanogenic digestion applied to a low pH acetic acid solution.
AB  - This paper discusses the methanogenic digestion of a synthetic acetic acid
      wastewater inoculated using a mixed culture obtained from an anaerobic digester
      at a municipal wastewater treatment facility. Experiments were conducted in 500mL
      batch reactors containing an unbuffered acetic acid solution. Test conditions
      compared methane production and acetic acid degradation at both acidic (pH 4.5)
      and neutral (pH 7.0) initial system conditions. Results showed that methane
      production increased by 30% when the initial pH was decreased from 7.0 to 4.5.

PMID- 16996265
TI  - The fat cadherin acts through the hippo tumor-suppressor pathway to regulate
      tissue size.
AB  - BACKGROUND: The Hippo tumor-suppressor pathway has emerged as a key signaling
      pathway that controls tissue size in Drosophila. Merlin, the Drosophila homolog
      of the human Neurofibromatosis type-2 (NF2) tumor-suppressor gene, and the
      related protein Expanded are the most upstream components of the Hippo pathway
      identified so far. However, components acting upstream of Expanded and Merlin,
      such as transmembrane receptors, have not yet been identified. RESULTS: Here, we
      report that the protocadherin Fat acts as an upstream component in the Hippo
      pathway. Fat is a known tumor-suppressor gene in Drosophila, and fat mutants have
      severely overgrown imaginal discs. We found that the overgrowth phenotypes of fat
      mutants are similar to those of mutants in Hippo pathway components: fat mutant
      cells continued to proliferate after wild-type cells stopped proliferating, and
      fat mutant cells deregulated Hippo target genes such as cyclin E and diap1. Fat
      acts genetically and biochemically upstream of other Hippo pathway components
      such as Expanded, the Hippo and Warts kinases, and the transcriptional
      coactivator Yorkie. Fat is required for the stability of Expanded and its
      localization to the plasma membrane. In contrast, Fat is not required for Merlin
      localization, and Fat and Merlin act in parallel in growth regulation.
      CONCLUSIONS: Taken together, our data identify a cell-surface molecule that may
      act as a receptor of the Hippo signaling pathway.

PMID- 16996266
TI  - The tumor-suppressor gene fat controls tissue growth upstream of expanded in the
      hippo signaling pathway.
AB  - BACKGROUND: The tight control of cell proliferation and cell death is essential
      to normal tissue development, and the loss of this control is a hallmark of
      cancers. Cell growth and cell death are coordinately regulated during development
      by the Hippo signaling pathway. The Hippo pathway consists of the Ste20 family
      kinase Hippo, the WW adaptor protein Salvador, and the NDR kinase Warts. Loss of
      Hippo signaling in Drosophila leads to enhanced cell proliferation and decreased
      apoptosis, resulting in massive tissue overgrowth through increased expression of
      targets such as Cyclin E and Diap1. The cytoskeletal proteins Merlin and Expanded
      colocalize at apical junctions and function redundantly upstream of Hippo. It is
      not clear how they regulate growth or how they are localized to apical junctions.
      RESULTS: We find that another Drosophila tumor-suppressor gene, the atypical
      cadherin fat, regulates both cell proliferation and cell death in developing
      imaginal discs. Loss of fat leads to increased Cyclin E and Diap1 expression,
      phenocopying loss of Hippo signaling. Ft can regulate Hippo phosphorylation, a
      measure of its activation, in tissue culture. Importantly, fat is needed for
      normal localization of Expanded at apical junctions in vivo. Genetic-epistasis
      experiments place fat with expanded in the Hippo pathway. CONCLUSIONS: Together,
      these data suggest that Fat functions as a cell-surface receptor for the Expanded
      branch of the conserved Hippo growth control pathway.

PMID- 16996267
TI  - Light-driven translocation of signaling proteins in vertebrate photoreceptors.
AB  - The dynamic localization of proteins within cells is often determined by
      environmental stimuli. In retinal photoreceptors, light exposure results in the
      massive translocation of three key signal transduction proteins, transducin,
      arrestin and recoverin, into and out of the outer segment compartment where
      phototransduction takes place. This phenomenon has rapidly taken the center stage
      of photoreceptor cell biology, thanks to the introduction of new quantitative and
      transgenic approaches. Here, we discuss evidence that intracellular protein
      translocation contributes to adaptation of photoreceptors to diurnal changes in
      ambient light intensity and summarize the current debate on whether it is driven
      by diffusion or molecular motors.

PMID- 16996268
TI  - Endocytosis: the DUB version.
AB  - Dynamic modification of endosomal cargo proteins, such as the epidermal growth
      factor receptor, by ubiquitin can regulate their sorting into the lumen of
      multivesicular bodies through interactions with a complex protein network
      incorporating the endosomal sorting complexes required for transport (ESCRTs).
      Two deubiquitinating enzymes, AMSH and UBPY, interact with ESCRT protein
      components but exert opposite effects upon the rate of epidermal growth factor
      receptor downregulation. This might reflect their distinct specificities for
      different types of polyubiquitin chain linkage. We propose that AMSH might rescue
      ubiquitinated cargo from lysosomal degradation through disassembly of K63-linked
      polyubiquitin chains. UBPY function is essential for effective downregulation but
      is likely to be multifaceted, encompassing activity against both K63-linked and
      K48-linked polyubiquitin chains and including regulation of the stability of
      ESCRT-associated proteins such as STAM, by reversing their ubiquitination.

PMID- 16996269
TI  - POZ for effect--POZ-ZF transcription factors in cancer and development.
AB  - The BTB/POZ-ZF [Broad complex, Tramtrack, Bric a brac (BTB) or poxvirus and zinc
      finger (POZ)-zinc finger] protein family comprises a diverse group of
      transcription factors. POZ-ZF proteins have been implicated in many biological
      processes, including B cell fate determination, DNA damage responses, cell cycle
      progression and a multitude of developmental events, including gastrulation, limb
      formation and hematopoietic stem cell fate determination. Consequently,
      dysfunction of vertebrate POZ-ZF proteins, such as promyelocytic leukemia zinc
      finger (PLZF), B cell lymphoma 6 (Bcl-6), hypermethylated in cancer 1 (HIC-1),
      Kaiso, ZBTB7 and Fanconi anemia zinc finger (FAZF), has been linked directly or
      indirectly to tumorigenesis and developmental disorders. Here, we discuss recent
      advances in the POZ-ZF field and the implications for the design of future
      studies to elucidate the biological roles of these unique transcription factors.

PMID- 16996270
TI  - The effects of auditory rhythms and instruction on walking patterns in
      individuals post stroke.
AB  - The objective was to investigate the effects of auditory rhythms and arm movement
      on inter-segmental coordination during walking in persons who have suffered a
      stroke. Eleven subjects walked on a treadmill: (1) during systematic increases in
      velocity (0.22-1.52 m/s), (2) with instructions to 'step to the beat' during
      systematic increases in metronome frequency (1-2.2 Hz), and (3) with
      instructions: 'move the arms and legs to the beat' during systematic increases in
      metronome frequency (1-2.2 Hz). Movement amplitude of upper and lower body
      segments, frequency coordination between arm and leg movements, phase relation
      between upper and lower body segments were measured. Moving the arms and legs to
      the beat resulted in increased arm swing along with 1:1 frequency coordination
      between the arm and leg, and a more out-of-phase relation between transverse
      pelvic and thoracic rotation was observed with larger pelvic and thoracic
      rotations. Verbal instructions to move the arms to the beat of a metronome leads
      to increased arm swing, increased stride length, but further study is needed to
      examine the dynamics of the changes in arm movement, to enhance understanding of
      how upper extremity movement dysfunction affects inter-segmental coordination
      during walking.

PMID- 16996271
TI  - Concurrent surgeries are a factor in predicting success of rectus transfer
      outcomes.
AB  - Cerebral palsy (CP) patients exhibit a wide range of functional responses to
      specific surgical interventions. The variability associated with surgical
      outcomes within this patient population precipitates the need to determine the
      functional effects in advance of the surgery. Pilot studies have indicated that
      the application of statistical models towards predicting functional outcomes of
      surgery produces clinically meaningful results. The purpose of this study was to
      evaluate the influence of pre-operative kinematic parameters in conjunction with
      concurrent surgeries on rectus transfer (RT) outcomes. Gait analysis data were
      collected from 68 patients (94 legs) pre- and post-operatively within a year of
      surgery. Patients were divided into four groups. Group 1 (N=14) contained only
      legs experiencing a rectus transfer. Group 2 (N=30) contained legs experiencing
      RT and hamstring lengthening (HL). Group 3 (N=7) contained legs experiencing RT
      and lower leg surgeries: either Achilles lengthening (AL), or gastrocnemius
      lengthening (GL). Finally, Group 4 (N=43) contained legs which experienced all
      four surgeries (RT+HL+AL+GL) concurrently. Multivariate jackknifed linear
      regression was used to predict the change in knee range of motion, DeltaROM, due
      to surgery on a group-by-group basis. In each case, the sole significant pre
      surgical variable was the range of motion. Group 1 legs had the best correlation
      (R=0.846) between pre-surgical ROM and DeltaROM whereas Group 4 legs had the
      worst correlation (R=0.661). Group 3 results were not significant. Group 1
      DeltaROM were also significantly lower as a whole, than all other groups, due to
      a larger percentage of patients needing the surgery to change timing of flexion
      in swing phase. When compared to modeling without consideration of surgery,
      modeling by surgical group produced results with fewer outliers and better
      correlation coefficients. Regardless of surgical group, patients with a lower pre
      surgical ROM (<40 degrees ) were more likely to experience an increase in ROM as
      a result of surgical intervention compared to their peers with an elevated pre
      surgical ROM who were likely to see a decrease in ROM. Pre-surgical ROM therefore
      serves as a useful predictor of outcome in rectus transfer surgery.

PMID- 16996272
TI  - Hyperimmune goat serum for amyotrophic lateral sclerosis.
AB  - The authors report a patient with amyotrophic lateral sclerosis (ALS) who showed
      a lessening of deterioration in respiratory muscle strength during treatment with
      hyperimmune goat serum (HGS) (Aimspro). Respiratory function tests (RFTs) were
      measured by established protocols, and all measurements were expressed as a
      percentage of normal predicted values. The rate of decline was calculated by
      linear regression analysis. Respiratory muscle strength decline was less during
      13 months of treatment with HGS (mean 1.3% per month, range 0.8-1.7%) compared to
      the preceding 13 months (mean 2.3% per month, range 1.2-3.1%), while a greater
      decline would be expected with disease progression. Comparison with similarly
      affected patients in the literature suggest that a decline of 4-5% per month of
      predicted values may be expected during the treatment phase.

PMID- 16996273
TI  - CO-metal interaction: Vital signaling from a lethal gas.
AB  - The past few years have witnessed intense research into the biological
      significance of carbon monoxide (CO) as an essential signaling mediator in cells
      and tissues. To transduce the signal properly, CO must react selectively with
      functional and structural proteins containing moieties that show preferred
      reactivity towards this gaseous molecule. This selectivity is exemplified by the
      interaction of CO with iron- and heme-dependent proteins, although systems
      containing other transition metals can potentially become a preferential target
      for CO. Notably, transition metal carbonyls, which carry and liberate CO, are
      also emerging as a pharmacological tool to mimic the bioactivity of endogenously
      generated CO. Thus, exploring how CO binding to metal complexes is translated
      into a cytoprotective function is a challenging task and might open up
      opportunities for therapeutic applications based on CO delivery.

PMID- 16996274
TI  - Perioperative in-stent thrombosis after lung resection performed within 3 months
      of coronary stenting.
AB  - BACKGROUND: Incidence of perioperative in-stent thrombosis associated with
      myocardial infarction in patients undergoing major lung resection within 3 months
      of coronary stenting. METHODS: Retrospective multi-institutional trial including
      all patients undergoing major lung resection (lobectomy or pneumonectomy) within
      3 months of coronary stenting with non-drug-eluting stents between 1999 and 2004.
      RESULTS: There were 32 patients (29 men and 3 women), with age ranging from 46 to
      82 years. One, two or four coronary stents were deployed in 72%, 22% and 6% of
      the patients, respectively. The time intervals between stenting and lung surgery
      were <30 days, 30-60 days and 61-90 days in 22%, 53% and 25% of the patients,
      respectively. All patients had dual antiplatelet therapy after stenting.
      Perioperative medication consisted of heparin alone or heparin plus aspirin in
      34% and 66% of the patients, respectively. Perioperative in-stent thrombosis with
      myocardial infarction occurred in three patients (9%) with fatal outcome in one
      (3%). Twenty patients underwent lung resection after 4 weeks of dual antiplatelet
      therapy as recommended by the ACC/AHA Guideline Update; however, two out of three
      perioperative in-stent thrombosis occurred in this group of patients.
      CONCLUSIONS: Major lung resection performed within 3 months of coronary stenting
      may be complicated by perioperative in-stent thrombosis despite 4 weeks of dual
      antiplatelet therapy after stenting as recommended by the ACC/AHA Guideline
      Update.

PMID- 16996275
TI  - Absorption and emission spectroscopic characterization of blue-light receptor
      Slr1694 from Synechocystis sp. PCC6803.
AB  - The BLUF protein Slr1694 from the cyanobacterium Synechocystis sp. PCC6803 is
      characterized by absorption and emission spectroscopy. Slr1694 expressed from E.
      coli which non-covalently binds FAD, FMN, and riboflavin (called Slr1694(I)), and
      reconstituted Slr1694 which dominantly contains FAD (called Slr1694(II)) are
      investigated. The receptor conformation of Slr1694 (dark adapted form Slr1694(r))
      is transformed to the putative signalling state (light adapted form Slr1694(s))
      with red-shifted absorption and decreased fluorescence efficiency by blue-light
      excitation. In the dark at 22 degrees C, the signalling state recovers back to
      the initial receptor state with a time constants of about 14.2s for Slr1694(I)
      and 17s for Slr1694(II). Quantum yields of signalling state formation of
      approximately 0.63+/-0.07 for both Slr1694(I) and Slr1694(II) were determined by
      transient transmission measurements and intensity dependent steady-state
      transmission measurements. Extended blue-light excitation causes some bound
      flavin conversion to the hydroquinone form and some photo-degradation, both with
      low quantum efficiency. The flavin-hydroquinone re-oxidizes slowly back (time
      constant 5-9 min) to the initial flavoquinone form in the dark. A photo-cycle
      dynamics scheme is presented.

PMID- 16996276
TI  - Ruby-Helix: an implementation of helical image processing based on object
      oriented scripting language.
AB  - Helical image analysis in combination with electron microscopy has been used to
      study three-dimensional structures of various biological filaments or tubes, such
      as microtubules, actin filaments, and bacterial flagella. A number of packages
      have been developed to carry out helical image analysis. Some biological
      specimens, however, have a symmetry break (seam) in their three-dimensional
      structure, even though their subunits are mostly arranged in a helical manner. We
      refer to these objects as "asymmetric helices". All the existing packages are
      designed for helically symmetric specimens, and do not allow analysis of
      asymmetric helical objects, such as microtubules with seams. Here, we describe
      Ruby-Helix, a new set of programs for the analysis of "helical" objects with or
      without a seam. Ruby-Helix is built on top of the Ruby programming language and
      is the first implementation of asymmetric helical reconstruction for practical
      image analysis. It also allows easier and semi-automated analysis, performing
      iterative unbending and accurate determination of the repeat length. As a result,
      Ruby-Helix enables us to analyze motor-microtubule complexes with higher
      throughput to higher resolution.

PMID- 16996277
TI  - Muscle activation during cycling at different cadences: effect of maximal
      strength capacity.
AB  - The purpose of this study was to examine the influence of maximal strength
      capacity on muscle activation, during cycling, at three selected cadences: a low
      cadence (50 rpm), a high cadence (110 rpm) and the freely chosen cadence (FCC).
      Two groups of trained cyclists were selected on the basis of the different
      maximal isokinetic voluntary contraction values (MVCi) of their lower extremity
      muscles as follow: F(min) (lower MVCi group) and F(max) (higher MVCi group). All
      subjects performed three 4-min cycling exercises at a power output corresponding
      to 80% of the ventilatory threshold under the three cadences. Neuromuscular
      activity of vastus lateralis (VL), rectus femoris (RF) and biceps femoris (BF)
      was studied quantitatively (integrated electromyography, IEMG) and qualitatively
      (timing of muscle bursts during crank cycle). Cadence effects were observed on
      the EMG activity of VL muscle and on the burst onset of the BF, VL and RF
      muscles. A greater normalized EMG activity of VL muscle was observed for the
      F(min) group than the F(max) group at all cadences (respectively F(min) vs.
      F(max) at 50 rpm: 17+/-5% vs. 38+/-6%, FCC: 22+/-7% vs. 44+/-5% and 110 rpm: 21+/
      6% vs. 45+/-6%). At FCC and 110 rpm, the burst onset of BF and RF muscles of the
      F(max) group started earlier in the crank cycle than the F(min) group These
      results indicate that in addition to the cadence, the maximal strength capacity
      influences the lower extremity muscular activity during cycling.

PMID- 16996278
TI  - Effects of abdominal stabilization maneuvers on the control of spine motion and
      stability against sudden trunk perturbations.
AB  - Much discussion exists about which is the most effective technique to improve
      spine stability. The purpose of this study was to evaluate the effectiveness of
      abdominal bracing and abdominal hollowing maneuvers to control spine motion and
      stability against rapid perturbations. Eleven healthy males were posteriorly
      loaded in different experimental conditions: resting with no knowledge of the
      perturbation timing; performing each of the stabilization maneuvers at 10%, 15%
      and 20% of internal oblique maximum voluntary contraction with no knowledge of
      the perturbation timing; and naturally coactivating the trunk muscles when
      perturbation timing was known. An EMG biofeedback system was used to control the
      pattern and intensity of abdominal coactivation. The muscular preactivation of
      seven trunk muscles (bilaterally registered), the applied force, and the torso
      muscular and kinematic responses to loading were measured; and the spine
      stability and compression were modeled. The hollowing maneuver was not effective
      for reducing the kinematic response to sudden perturbation. On the contrary, the
      bracing maneuver fostered torso cocontraction, reduced lumbar displacement, and
      increased trunk stability, but at the cost of increasing spinal compression. When
      the timing of the perturbation was known, the participants were able to stabilize
      the trunk while imposing smaller spine compressive loads.

PMID- 16996279
TI  - Cortical trapping of alpha-[(11)C]methyl-l-tryptophan, an index of serotonin
      synthesis, is lower in females than males.
AB  - One neural system that may exhibit gender differences is serotonin (5-HT), a
      neurotransmitter implicated in the regulation of mood, cognitive processes, and
      impulse-control. However, most of the available evidence of gender-related
      differences in this system has been indirect and at times contradictory. The
      objective of the present study was to follow up on preliminary evidence that
      there are gender differences in brain regional 5-HT synthesis, as measured by
      trapping of alpha-[(11)C]methyl-l-tryptophan (alpha-[(11)C]MTrp). Sixty-minute
      dynamic scans were performed in healthy volunteers, 28 women and 31 men.
      Functional images of the brain trapping constant, used as a proxy for 5-HT
      synthesis, which correlate in the rat brain with tryptophan's conversion into 5
      HT, were transferred to the standardized 3D space. The voxel based comparison was
      performed by Statistical Parametric Mapping with proportional normalization.
      There was lower normalized alpha-[(11)C]MTrp trapping in females than males
      throughout much of the cerebral cortex, including the left middle frontal gyrus,
      the bilateral inferior frontal gyrus, the bilateral precentral gyrus, the left
      supramarginal gyrus, the bilateral inferior parietal lobule, the left superior
      temporal gyrus, the bilateral posterior cingulate gyrus, and the bilateral
      precuneus. There were no regions in which the normalized trapping was
      significantly higher in females than in males. Gender differences in sub-cortical
      sites were not found. Women, compared to men, may have lower rates of this tracer
      trapping, used as a proxy for 5-HT synthesis, throughout much of the cerebral
      cortex which is likely related to differences in 5-HT synthesis because relative
      differences in the normalized trapping should be the same as those in 5-HT
      synthesis. These differences may be related, at least in part, to previously
      suggested gender differences in affect, cognitive processes, and susceptibility
      to 5-HT-related neuropsychiatric and neurological disorders.

PMID- 16996280
TI  - Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility
      contrast perfusion MR imaging at 3.0 T.
AB  - This study aimed to determine regional pattern of tissue perfusion in the normal
      appearing white matter (NAWM) of patients with primary-progressive (PP),
      relapsing-remitting (RR) multiple sclerosis (MS) and healthy controls, and to
      investigate the association between perfusion abnormalities and clinical
      disability. Using dynamic susceptibility contrast (DSC) perfusion MRI at 3 T, we
      studied 22 patients with clinically definite MS, 11 with PP-MS and 11 with RR-MS
      and 11 age- and gender-matched healthy volunteers. The MRI protocol included
      axial dual-echo, dynamic susceptibility contrast enhanced (DSC) T2*-weighted and
      post-contrast T1-weighted images. Absolute cerebral blood flow (CBF), cerebral
      blood volume (CBV) and mean transit time (MTT) were measured in the
      periventricular, frontal, occipital NAWM and in the splenium of the corpus
      callosum. Compared to controls, CBF and CBV were significantly lower in all NAWM
      regions in both PP-MS patients (p values from <0.0001 to 0.001) and RR-MS (p
      values from <0.0001 to 0.020). Compared to RR-MS, PP-MS patients showed
      significantly lower CBF in the periventricular NAWM (p=0.002) and lower CBV in
      the periventricular and frontal NAWM (p values: 0.0029 and 0.022). EDSS was
      significantly correlated with the periventricular CBF (r=-0.48, p=0.0016) and
      with the periventricular and frontal CBV (r=-0.42, p=0.015; r=-0.35, p=0.038,
      respectively). This study suggests that the hemodynamic abnormalities of NAWM
      have clinical relevance in patients with MS. DSC perfusion MRI might provide a
      relevant objective measure of disease activity and treatment efficacy.

PMID- 16996281
TI  - Ictal paralysis with tonic eye gazing mimicking a pontine infarction.
AB  - PURPOSE: Concomitant positive and negative motor phenomena in a single seizure
      have not been reported before. METHOD: We used an extensive history review,
      neurological examination, EEG, MRI and SPECT study to demonstrate a rare
      combination of motor presentations as an ictal phenomenon. RESULT: A 64-year-old
      male was brought to the emergency room with dizziness, progressive drowsiness and
      left hemiparesis. A spontaneous eye deviation to the left side with nystagmus was
      observed. A right pontine lesion was tentatively diagnosed. However, a focal
      motor seizure of the patient's left face and limbs occurred 3.5h later. A brain
      MRI revealed a high signal in the right amygdala, hippocampus and thalamus,
      instead of the pons. An EEG showed periodic epileptic discharges in the right
      posterior temporal parietal region. Regional hyperperfusion was found by brain
      SPECT. The level of consciousness improved dramatically after adequate phenytoin
      treatment. CONCLUSION: A posterior temporal-parietal seizure can present with a
      prolonged ictal paralysis, a positive ocular nystagmoid deviation and an altered
      level of consciousness. The EEG is essential for a correct diagnosis, especially
      with a negative or an unexplainable MRI study. The SPECT has an additional role
      for the differential diagnosis.

PMID- 16996282
TI  - Pharmacophore identification and virtual screening for methionyl-tRNA synthetase
      inhibitors.
AB  - Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes involved in protein
      biosynthesis in all living organisms and are an unexploited antibacterial
      targets, as many strains of bacteria have become resistant to all established
      classes of antibiotics. Therefore, the main aim of this study is to discover new
      lead molecules which would be useful as anti-bacterial compounds. Pharmacophore
      models were developed by using CATALYST HypoGen with a training set of 29 diverse
      methionyl-tRNA synthetase (MetRS) inhibitors. The best quantitative pharmacophore
      hypothesis (Hypo1) obtained a correlation coefficient of 0.975, root mean square
      deviation (RMSD) of 0.55 and cost difference (null cost-total cost) of 70.32.
      This Hypo1 was validated by two methods, first by using 104 test set molecules
      which resulted a correlation of 0.926 between HypoGen estimated activities versus
      experimental activities and secondly by Cat-Scramble validation method. This
      validated pharmacophore model was further used for screening databases for
      discovery of new MetRS inhibitors. The new lead compounds were further analyzed
      for drug-like properties. Homology modeled structure of Staphylococcus aureus
      MetRS was built and molecular docking studies were performed with many inhibitors
      using the newly built protein structure. Finally, it was found that the new leads
      exhibited good estimated inhibitory activity, calculated binding properties
      similar to experimentally proven compounds and also favorable drug-like
      properties.

PMID- 16996283
TI  - Localization and diurnal variations of carbonic anhydrase mRNA expression in the
      inner ear of the rainbow trout Oncorhynchus mykiss.
AB  - Physiological studies have suggested that carbonic anhydrase (CA) plays a central
      role in otolith biomineralization via ion transport. However, the presence and
      exact function of CA in the inner ear have not been determined. In the present
      study, to investigate the localization of CA and its involvement in otolith
      calcification, we cloned two cDNAs encoding CAs from the rainbow trout sacculus.
      These two cDNAs, designated rainbow trout CAa (rtCAa) and rtCAb, both had an open
      reading frame encoding 260 amino acids with a sequence identity of 78%.
      Remarkably, rtCAb has a high degree of homology (82%) with "high activity CA" in
      the zebrafish, and its mRNA expression showed variation in the range 1.9-11.4 x
      10(4) copies/ng total RNA in the sacculus. In contrast, rtCAa mRNA was constantly
      expressed at approximately 3 x 10(4) copies/ng total RNA. In situ hybridization
      revealed that rtCAb mRNA was strongly expressed in the distal squamous epithelial
      cells and transitional epithelial cells, except the mitochondria-rich cells,
      whereas, rtCAa was localized in extrasaccular tissue. These results suggest that
      the rtCAb isozyme is involved in the daily increment formation and calcification
      of otoliths via phase and spatial differences of the bicarbonate supply to the
      endolymph.

PMID- 16996284
TI  - Cloning of cDNAs and hybridization analysis of lysozymes from two oyster species,
      Crassostrea gigas and Ostrea edulis.
AB  - In bivalve molluscs including oysters, lysozymes play an important role in the
      host defense mechanisms against invading microbes. However, it remains unclear in
      which sites/cells the lysozyme genes are expressed and which subsequently
      produced the enzyme. This study cloned lysozyme cDNAs from the digestive organs
      of Pacific oyster Crassostrea gigas and European flat oyster Ostrea edulis. Both
      complete sequences of two oysters' lysozymes were composed of 137 amino acids.
      Two translated proteins present a high content in cysteine residues. Phylogenetic
      analyses showed that these oysters' lysozymes clustered with the invertebrate
      type lysozymes of other bivalve species. In the Pacific oyster, lysozyme mRNA was
      expressed in all tissues except for those of the adductor muscle. In situ
      hybridization analyses revealed that lysozyme mRNA was expressed strongly in
      basophil cells in the digestive gland tubule of C. gigas, but not in digestive
      cells. Results indicated that the basophil cells of the oyster digestive gland
      are the sites of lysozyme synthesis.

PMID- 16996285
TI  - Comparison of seasonal dynamics of the essential PUFA contents in benthic
      invertebrates and grayling Thymallus arcticus in the Yenisei river.
AB  - Seasonal dynamics of contents of essential polyunsaturated fatty acids (PUFA) in
      dominant groups of benthic invertebrates: gammarids (Gammaridae, Amphipoda),
      oligochaetes (Oligochaeta), chironomid larvae (Chironomidae, Diptera) and
      caddisfly larvae (Trichoptera), and dominant benthivorous fish, Siberian grayling
      Thymallus arcticus, have been studied in ecosystem of the large Siberian river.
      During the year of the study most benthic invertebrate taxa showed significant
      variations in the contents of both C-18 and long chain C-20-22 PUFAs. In
      contrast, the fish, which consumed the zoobenthos, had no significant seasonal
      variations in long chain PUFAs' contents. Thereby, the fish, as organisms of
      relatively higher evolution level than invertebrates, was supposed to have more
      strict metabolic control of long chain PUFAs' contents. Evidence was obtained
      that the studied fish species, grayling, may be capable to convert dietary EPA
      into DHA.

PMID- 16996286
TI  - Molecular cloning of the heat-shock cognate 70 (Hsc70) gene from the two-spotted
      spider mite, Tetranychus urticae, and its expression in response to heat shock
      and starvation.
AB  - We isolated a heat shock cognate 70 (hsc70) gene from the two-spotted spider
      mite, Tetranychus urticae, a serious agricultural pest. The hsc70 cDNA is 2275 bp
      and contains a 1962 bp open reading frame. The translated amino acid sequence
      consists of 654 residues with a calculated molecular mass of 71,275 Da and an
      isoelectronic point (pI) of 5.52. It also contains the highly conserved
      functional motifs of the Hsp70 family. A comparison of the deduced amino acid
      sequence shows a high identity (81-84%) with Hsp70s/Hsc70s of insects but the
      highest identity is with mussel Hsc71 (86%). Northern blot hybridization
      indicates that the hsc70 transcript level of female adults is higher than that of
      male adults. We evaluated the response of hsc70 gene to stresses from temperature
      and starvation. The level of hsc70 mRNA was not significantly changed by heat and
      cold shocks nor by recovery after the shocks. However, the hsc70 mRNA level was
      decreased by food restriction of female mites. Analysis of nucleotide and deduced
      amino acid sequences of hsc70 gene from T. urticae suggests that it is a member
      of heat shock cognate 70 gene in the highly conserved Hsp70 family but that its
      expression is influenced by food restriction rather than thermal stress. This is
      the first molecular analysis of a heat shock protein gene in an acarid.

PMID- 16996287
TI  - Identification of 16 new disease-causing mutations in the CPT2 gene resulting in
      carnitine palmitoyltransferase II deficiency.
AB  - The exonic regions of the carnitine palmitoyltransferase 2 (CPT2) gene were
      characterized from 101 patients with defined clinical and biochemical evidence
      for the adult onset form of CPT II deficiency and in 2 patients detected as
      newborns with abnormal acylcarnitine profiles. Twenty-seven disease-causing
      mutations within the CPT2 gene were identified in this cohort, 16 of which were
      novel. A total of 60 disease-causing mutations have been identified to date in
      CPT2 and 41 of these are predicted to produce amino acid substitution/deletions.
      The implications of these mutations are described in light of recent advances in
      our understanding of the molecular structure of members of the carnitine
      acyltransferase family.

PMID- 16996288
TI  - Effects of higher dietary protein intake on energy balance and metabolic control
      in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or
      trifunctional protein (TFP) deficiency.
AB  - The incidence of overweight and obesity is increasing among children with long
      chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or mitochondrial trifunctional
      (TFP) deficiency. Traditional treatment includes fasting avoidance and
      consumption of a low-fat, high-carbohydrate diet. A diet higher in protein and
      lower in carbohydrate may help to lower total energy intake while maintaining
      good metabolic control. To determine the short-term safety and efficacy of a high
      protein diet, subjects were admitted to the General Clinical Research Center and
      fed an ad-libitum high-protein diet and a high-carbohydrate diet for 6 days each
      using a randomized, crossover design. Nine subjects with LCHAD or TFP deficiency,
      age 7-14 were enrolled. Body composition was determined by DEXA. Total energy
      intake was evaluated daily. Resting energy expenditure and substrate utilization
      were determined by indirect calorimetry. Post-prandial metabolic responses of
      plasma glucose, insulin, leptin, ghrelin, acylcarnitines, and triglyceride were
      determined in response to a liquid meal. Subjects had a higher fat mass, lower
      lean mass and higher plasma leptin levels compared to reference values. While on
      the high protein diet energy consumption was an average of 50 kcals/day lower (p
      = 0.02) and resting energy expenditure was an average of 170 kcals/day higher (p
      = 0.05) compared to the high carbohydrate diet. Short-term higher protein diets
      were safe, well tolerated, and resulted in lowered energy intake and increased
      energy expenditure than the standard high-carbohydrate diet. Long-term studies
      are needed to determine whether higher protein diets will reduce the risk of
      overweight and obesity in children with LCHAD or TFP deficiency.

PMID- 16996289
TI  - Sjogren-Larsson syndrome: molecular genetics and biochemical pathogenesis of
      fatty aldehyde dehydrogenase deficiency.
AB  - Sjogren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by
      mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase (FALDH),
      an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. Affected
      patients display ichthyosis, mental retardation and spastic diplegia. More than
      70 mutations in ALDH3A2 have been discovered in SLS patients including amino acid
      substitutions, deletions, insertions and splicing errors. Most mutations are
      private, but several common mutations reflect founder effects, consanguinity or
      recurrent mutational events. FALDH oxidizes fatty aldehyde substrates arising
      from metabolism of fatty alcohols, leukotriene B4, ether glycerolipids and other
      potential sources such as sphingolipids. The pathogenesis of the cutaneous and
      neurologic symptoms is thought to result from abnormal lipid accumulation in the
      membranes of skin and brain; the formation of aldehyde Schiff base adducts with
      amine-containing lipids or proteins; or defective eicosanoid metabolism.
      Therapeutic approaches are being developed to target specific metabolic defects
      associated with FALDH deficiency or to correct the genetic defect by gene
      transfer.

PMID- 16996290
TI  - Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh syndrome.
AB  - We describe a novel mitochondrial ND2 mutation (T4681C) in a patient presenting
      with Leigh Syndrome. Biochemical analyses revealed a low isolated complex I
      activity in patient's fibroblasts, blood and skeletal muscle. Mutant
      transmitochondrial cybrid clones retained the specific complex I defect,
      demonstrating the mitochondrial genetic origin of the disease. The mutation leads
      to a L71P substitution at an evolutionary conserved amino acid stretch. By two
      dimensional blue native electrophoresis (2D-BN-SDS-PAGE), decreased complex I
      levels were observed together with an accumulation of specific assembly
      intermediates, suggesting that the mutation disturbs the complex I assembly
      pathway.

PMID- 16996291
TI  - Structural basis for processivity and single-strand specificity of RNase II.
AB  - RNase II is a member of the widely distributed RNR family of exoribonucleases,
      which are highly processive 3'-->5' hydrolytic enzymes that play an important
      role in mRNA decay. Here, we report the crystal structure of E. coli RNase II,
      which reveals an architecture reminiscent of the RNA exosome. Three RNA-binding
      domains come together to form a clamp-like assembly, which can only accommodate
      single-stranded RNA. This leads into a narrow, basic channel that ends at the
      putative catalytic center that is completely enclosed within the body of the
      protein. The putative path for RNA agrees well with biochemical data indicating
      that a 3' single strand overhang of 7-10 nt is necessary for binding and
      hydrolysis by RNase II. The presence of the clamp and the narrow channel provides
      an explanation for the processivity of RNase II and for why its action is limited
      to single-stranded RNA.

PMID- 16996292
TI  - [Knowledge, attitudes and practices about blood donation. A sociological study
      among the population of Lome in Togo].
AB  - GOALS: 1) analyse the knowledge, attitudes and practices of Lome population about
      blood donation; 2) identify obstacles to blood donation among the population of
      Lome; 3) suggest some solutions to improve the performance of the National Blood
      Transfusion Centre (CNTS). METHODOLOGY: We have conducted a sample survey among
      the population of Lome from the 6th to 21st October 2003. Three hundred persons
      filled a questionnaire. RESULTS: In the sample, 183 (61%) were males. Their age
      ranged from 18 to 67 years with 2/3 of young peoples between 18 and 37 years.
      Pupils/students were 24,33%, wage-earners, 55% and the unemployed, 17,67%. More
      than the half of the investigated persons (54,67%) were unmarried and 96, 33%
      persons were literate. Nearly all the people (96,33%) knew about blood donation
      in Lome and they have received information mainly from friends, media and
      sensitization by the CNTS. Sixty-one percent of the investigated knew where blood
      is donated. All the investigated were unanimous about the vital role of blood.
      Whatever their religion, they recognized its sacred nature. The majority of the
      investigated (85%) were willing to donate blood. Only 95 people were donors. The
      reasons for non-donation were mainly related to the fear of catching diseases
      (31,71%) especially the HIV (9,76%), the lack of information (25,37%), the
      religious beliefs (19,51%) and the fear of knowing the result of one's HIV test.
      277 people (92,33%) said that blood should be donated without remuneration.
      CONCLUSION: There is a growing interest in the blood donation among the
      population of Lome but new strategies must be elaborated to inform the population
      and motivate blood donors.

PMID- 16996293
TI  - Hyperamylasemia and back pain: an exceptional association revealing multiple
      myeloma.

PMID- 16996294
TI  - Comparative study of sonochemical reactors with different geometry using thermal
      and chemical probes.
AB  - Laboratory scale 20 kHz sonochemical reactors with different geometries have been
      tested using thermal probes, the kinetics of H(2)O(2) formation, and the kinetics
      of diphenylmethane (DPhM) sonochemical darkening. Results revealed that the
      overall sonochemical reaction rates in H(2)O and DPhM are driven by the total
      absorbed acoustic energy and roughly independent the geometry of the studied
      reactors. However, the sonochemical efficiency, defined as eta=VG/S, where G is a
      sonochemical yield of H(2)O(2), V is a volume of sonicated liquid, and S is a
      surface of the sonotrode, was proved to increase with the decrease of S. This
      phenomenon was explained by growing of the maximum cavitating bubble size with
      ultrasonic intensity and its independence towards the specific absorbed acoustic
      power. For the cleaning bath reactor the kinetics of the sonochemical reactions
      in H(2)O and DPhM depends strongly on the reaction vessel materials: the reaction
      rates decreased with the increase of the materials elasticity. Kinetic study of
      H(2)SO(4) sonolysis using a sonoreactor without direct contact with titanium
      sonotrode showed that sulphate anion is an effective scavenger of OH() radicals
      formed during water sonolysis.

PMID- 16996295
TI  - Analysis of the effect of partial vitrification on stress development in
      cryopreserved blood vessels.
AB  - Thermal stress development in blood vessels, during processes associated with
      vitrification (vitreous means glassy in Latin), is studied. This paper addresses
      the limiting case where the specimen completely crystallizes, while the
      cryoprotectant medium (CPA) completely vitrifies. This case is expected to
      provide upper boundary estimates for stresses for the more common problem of a
      partially vitrified sample. The CPA is modeled as a linear viscoelastic medium,
      with viscosity increasing exponentially with decreasing temperature; given the
      assumption of complete crystallization, the blood vessel is modeled as linear
      elastic below the freezing temperature. Consistent with previous observations,
      the CPA is found to behave linear elastically below a set-temperature, at which
      point the viscosity rises sufficiently quickly with further cooling. This
      observation reduces computational efforts and allows for parametric studies based
      on suitably chosen wholly elastic models. Both 2D concentric cylinder models of
      the blood vessel in a straight configuration and a 3D model of the vessel curled
      in a vial of CPA are studied; 2D models are shown to bound the results of the
      more general 3D problem. It is found that stress in the CPA decreases with
      increase in CPA volume, at least under conditions where the temperature can be
      viewed as uniform. Planar cracks are predicted to form transverse to the vessel
      axis, and to propagate right up to the blood vessel wall. Should such cracks
      propagate into the vessel, even over only a few mum, the mechanical damage to the
      lumen, or to endothelial cells, may cause the blood vessel to completely loose
      its functionality at the end of the cryopreservation protocol.

PMID- 16996296
TI  - Alteration of intracellular GSH levels and its role in microcystin-LR-induced DNA
      damage in human hepatoma HepG2 cells.
AB  - Microcystin-LR (MCLR) is a liver-specific toxin known as a tumour promoter in
      experimental animals. Its mechanisms of hepatotoxicity have been well documented;
      however, the mechanisms of other effects, in particular those related to its
      genotoxicity, are not well understood. In our previous studies, we showed that
      MCLR-induced DNA strand breaks are transiently present and that the damage is
      mediated by reactive oxygen species (ROS). In this study, we show that exposure
      of HepG2 cells to non-cytotoxic doses of MCLR-induced time-dependent alterations
      in the level of intracellular reduced glutathione (GSH). These comprised a rapid
      initial decrease followed by a gradual increase, reaching a maximum after 6h of
      exposure, before returning to the control level after 8h. During the first 4h,
      expression of glutamate-cysteine ligase (GCL), the rate-limiting enzyme of GSH
      synthesis, increased, indicating an increased rate of de novo synthesis of GSH.
      The most important observation of this study, combined with the results of our
      previous studies is the correlation between the time course of alterations of
      intracellular GSH content and the formation and disappearance of MCLR-induced DNA
      damage. When the intracellular GSH level was reduced, MCLR-induced DNA damage was
      observed to increase. Later, when the level of intracellular GSH was normal or
      elevated, new DNA damage was not induced and existing damage was repaired. To
      confirm the role of GSH system in MCLR-induced genotoxicity, the intracellular
      GSH level was moderated by pre-treatment with buthionine-(S,R)-sulfoximine (BSO),
      a specific GSH synthesis inhibitor, and with N-acetylcysteine (NAC), a GSH
      precursor. Pre-treatment with BSO dramatically increased the susceptibility of
      HepG2 cells to MCLR-induced DNA damage, while pre-treatment with NAC almost
      completely prevented MCLR-induced DNA damage. Thus, intracellular GSH is shown to
      play a critical role in the cellular defence against MCLR-induced DNA damage in
      HepG2 cells.

PMID- 16996297
TI  - Vibrational spectroscopy investigation using ab initio and density functional
      theory analysis on the structure of 2-amino-5-methylphenol.
AB  - The laser Raman and Fourier transform infrared spectra of 2-amino-5-methylphenol
      were recorded in the solid phase. The equilibrium geometry, harmonic vibrational
      frequencies, infrared intensities, Raman scattering activities, depolarization
      ratios and reduced masses were calculated by HF and density functional B3LYP
      methods by using 6-311+G(d,p) basis set. The scaled theoretical wavenumbers
      showed very good agreement with the experimental values. The thermodynamic
      functions of the title compound were also performed at HF/6-31G(d,p)/6-311+G(d,p)
      and B3LYP/6-31G(d,p)/6-311+G(d,p) levels of theory. A detailed interpretations of
      the infrared and Raman spectra of 2-amino-5-methylphenol is reported. The
      theoretical spectrograms for FT-IR spectra of the title molecule have been
      constructed.

PMID- 16996298
TI  - An end user evaluation of query formulation and results review tools in three
      medical meta-search engines.
AB  - PURPOSE: Retrieving sufficient relevant information online is difficult for many
      people because they use too few keywords to search and search engines do not
      provide many support tools. To further complicate the search, users often ignore
      support tools when available. Our goal is to evaluate in a realistic setting when
      users use support tools and how they perceive these tools. METHODS: We compared
      three medical search engines with support tools that require more or less effort
      from users to form a query and evaluate results. We carried out an end user study
      with 23 users who were asked to find information, i.e., subtopics and supporting
      abstracts, for a given theme. We used a balanced within-subjects design and
      report on the effectiveness, efficiency and usability of the support tools from
      the end user perspective. CONCLUSIONS: We found significant differences in
      efficiency but did not find significant differences in effectiveness between the
      three search engines. Dynamic user support tools requiring less effort led to
      higher efficiency. Fewer searches were needed and more documents were found per
      search when both query reformulation and result review tools dynamically adjust
      to the user query. The query reformulation tool that provided a long list of
      keywords, dynamically adjusted to the user query, was used most often and led to
      more subtopics. As hypothesized, the dynamic result review tools were used more
      often and led to more subtopics than static ones. These results were corroborated
      by the usability questionnaires, which showed that support tools that dynamically
      optimize output were preferred.

PMID- 16996299
TI  - Reducing depression stigma using a web-based program.
AB  - OBJECTIVE: This study was designed to investigate the efficacy and feasibility of
      a web-based depression stigma education tool for healthcare professionals.
      METHODS: A web-based depression stigma program utilizing adult learning theories
      was developed. Forty-two consecutive subjects were enrolled from University of
      Maryland staff and graduate students. Primary outcomes were Bogardus Social
      Distance Scale with a vignette on major depression disorder (BSDS-MDD) and the
      Depression Stigma Scale (DSS) administered before and after the intervention.
      RESULTS: Internet-based education significantly decreased the level of depression
      stigma (BSDS-MDD 10.6+/-4.4 versus 7.2+/-4.4, p<0.001; DSS-personal 12.7+/-7.2
      versus 7.8+/-5.3, p<0.001; DSS-perceived 21.7+/-5.5 versus 12.4+/-5.5, p<0.001).
      After the educational intervention the subjects' knowledge about depression
      significantly improved (pre-test DKS=18.2+/-8.2 versus post-test DKS=20.6+/-4.1,
      p<0.001). The program was very well accepted by participants. For 100% of
      participants, it was not difficult to operate the program. CONCLUSIONS: Computer
      assisted education was effective in reducing the stigma of depression and
      increasing knowledge about depressive disorder. A web-based intervention has the
      potential to be used for educating graduate students and university staff about
      depression and for reducing depression stigmata. Healthcare professionals
      interacting with people with stigmatizing conditions can benefit from web-based
      computer education.

PMID- 16996300
TI  - The liver as a target organ of retinoids.
AB  - Retinoids have several biological functions including cell growth,
      differentiation and apoptosis. In liver, retinoids are known to be associated
      with regeneration, fibrosis and carcinogenesis. The facts that retinoid droplets
      in stellate cells are lost with progression of liver disease and that
      effectiveness of an acyclic retinoid on second primary liver cancer suggest the
      importance of liver as a target organ of retinoids. Our recent work has indicated
      that retinoids have antioxidant effects in association with regulation of fatty
      acid metabolism. In this review article, we discussed the important function of
      retinoids in liver, mainly from molecular aspects.

PMID- 16996301
TI  - Experimental muscle pain changes the spatial distribution of upper trapezius
      muscle activity during sustained contraction.
AB  - OBJECTIVE: To investigate the effect of local excitation of nociceptive muscle
      afferents on the spatial distribution of muscle activity. METHODS: Surface
      electromyographic (EMG) signals were recorded from the upper trapezius muscle of
      10 healthy volunteers with a 5 x 13 electrode grid during 90-s isometric
      contractions before, during, 15 and 30 min after intramuscular injection of
      hypertonic (painful) or isotonic (non-painful) saline. From the multi-channel EMG
      recordings, two-dimensional maps of root mean square and mean power frequency
      were obtained. The centre of gravity of the root mean square map was used to
      quantify global changes in the spatial distribution of muscle activity. RESULTS:
      During sustained contractions, average root mean square increased, average mean
      frequency decreased and the centre of gravity moved cranially. During
      experimental muscle pain, compared to before injection, the average root mean
      square decreased and there was a caudal shift of the centre of gravity. Fifteen
      minutes after the painful injection the centre of gravity returned to its
      original position. CONCLUSIONS: Short-term dynamic reorganization of the spatial
      distribution of muscle activity occurred in response to nociceptive afferent
      input. SIGNIFICANCE: The study furnishes an extension of the pain adaptation
      model indicating heterogeneous inhibition of muscle activity.

PMID- 16996302
TI  - Decreased input to the motor cortex increases motor cortical excitability.
AB  - OBJECTIVE: To investigate whether a short-duration reduction of input to the
      motor cortex affects excitability in the hand region of the motor cortex.
      METHODS: Subjects (n=10) received sets of transcranial magnetic stimulation of
      the motor cortex (TMS) and peripheral ulnar nerve stimulation. Stimuli were
      delivered before and after 20 min of inactivity of the test hand. The evoked
      compound muscle action potentials were recorded in two relaxed intrinsic hand
      muscles using surface EMG. RESULTS: Motor evoked potential size (MEP; expressed
      relative to the maximal M-wave) increased by approximately 30-40 in both hand
      muscles (P=0.012) following inactivity. The enlarged MEP was not associated with
      changes in F-wave size, a marker of motoneurone excitability, or changes in
      intracortical inhibition and facilitation measured with paired-pulse TMS.
      CONCLUSIONS: MEP growth most likely reflects an increase in motor cortical
      excitability. The increased excitability appears to be more associated with
      reduced voluntary drive to and from the motor cortex rather than reduced afferent
      input from the periphery. SIGNIFICANCE: These results have important implications
      for any investigation of motor cortical excitability in relaxed subjects. The
      outcome of an experimental intervention is the net result of the intervention
      itself and alterations in cortical excitability produced by the subjects'
      inactivity.

PMID- 16996304
TI  - Seizure or convulsive syncope during 1-Hz rTMS?

PMID- 16996303
TI  - A theoretical basis for standing and traveling brain waves measured with human
      EEG with implications for an integrated consciousness.
AB  - OBJECTIVE: We propose a theoretical framework for EEG and evoked potential
      studies based on the single postulate that these data are composed of a
      combination of waves (as this term is used in the physical sciences) and
      thalamocortical network activity. METHODS: Using known properties of traveling
      and standing waves, independent of any neocortical dynamic theory, our simple
      postulate leads to experimental predictions, several of which have now been
      verified. A mathematical-physiological theory of "brain waves" based on known
      (but highly idealized) properties of cortical synaptic action and corticocortical
      fibers is used to support the framework. RESULTS: Brain waves are predicted with
      links between temporal frequencies and the spatial distributions of synaptic
      activity. Such dispersion relations, which essentially define more general
      phenomena as waves, are shown to restrict the spatial-temporal dynamics of
      synaptic action with many experimental EEG consequences. CONCLUSIONS: The
      proposed framework accounts for several salient features of spontaneous EEG and
      evoked potentials. SIGNIFICANCE: We conjecture that wave-like behavior of
      synaptic action may facilitate interactions between remote cell assemblies,
      providing an important mechanism for the functional integration underlying
      conscious experience.

PMID- 16996305
TI  - Dependent edema and ascites associated with CPAP/BiPAP treatment of sleep apnea.

PMID- 16996306
TI  - Insomniac complaints interfere with quality of life but not with absenteeism:
      respective role of depressive and organic comorbidity.
AB  - BACKGROUND AND PURPOSE: Insomnia is common and associated with poor health status
      and quality of life. We designed a study to evaluate the impact of insomniac
      complaints with and without comorbidity on health status and absenteeism.
      PATIENTS AND METHODS: This is a cross-sectional study performed within a 1-year
      follow up study on a prospective cohort of French employees. Insomniac subjects
      (n=986) were compared to control subjects (n=584). Insomniacs suffering from self
      reported depressive feelings and behavioral and organic sleep complaints were
      excluded. RESULTS: Subjects with insomniac complaints (whether with mood or
      behavioral and organic sleep complaints or not) reported poorer quality of life
      and had a higher absenteeism rate than controls (9.6+/-31 versus 5.8+/-19 days,
      P<0.01). A logistic regression model adjusting for depressive and behavioral and
      organic sleep complaints showed that insomniac complaints were no longer
      predictive of absenteeism. CONCLUSIONS: Insomniac complaints are strongly
      associated with deterioration in quality of life but not necessarily with higher
      absenteeism.

PMID- 16996307
TI  - Are physicians aware of obstructive sleep apnea in children?
AB  - BACKGROUND AND PURPOSE: Childhood obstructive sleep apnea (OSA) affects 1-3% of
      preschool children. If left untreated, it can result in serious morbidity
      including growth retardation, cor pulmonale, and neurocognitive deficits, such as
      poor learning and behavioral problems. Early recognition and treatment is
      important to prevent morbidity and sequela and to provide better quality of life
      both for the child and his or her family members. The purpose of this study was
      to elucidate the knowledge and attitude physicians have about pediatric OSA,
      using the Obstructive Sleep Apnea Knowledge and Attitudes in Children (OSAKA
      KIDS) questionnaire. PATIENTS AND METHODS: The first section of the OSAKA-KIDS
      questionnaire, which includes 18 items presented in a true-or-false format, was
      developed to assess the knowledge physicians have about pediatric OSA. The second
      section, including five items, was developed to assess attitudes and was measured
      on a five-point Likert scale ranging from 1 to 5. RESULTS: A total of 230
      questionnaires were completed by physicians: 138 (60.3%) pediatricians, 70
      (30.5%) general practitioners and 21 (9.2%) pulmonologists. The mean total
      knowledge score was 66.7%. The knowledge score positively correlated with having
      sub-specialty training (r=0.205, P=0.002) and negatively correlated with having a
      higher degree (r=-0.283, P<0.001). The mean total attitude score was 3.4. The
      knowledge score positively correlated with the attitude score (r=0.27, P<0.001).
      CONCLUSIONS: This study shows that among physicians there are deficits in
      knowledge about childhood OSA and its treatment. More focused educational
      programs are needed within medical schools and within pediatric residency and
      post-graduate training programs.

PMID- 16996308
TI  - A model of coronary artery endothelial dysfunction in the sleeping lamb.
AB  - BACKGROUND AND PURPOSE: Much remains unknown about the regulation of coronary
      artery blood flow (CBF), particularly during sleep and sleep-related disease
      states such as obstructive sleep apnoea (OSA). Mediators produced by the
      endothelium are known to be crucial in the regulation of CBF, particularly
      vasodilator substances such as nitric oxide. Endothelial dysfunction with altered
      vascular reactivity has been identified in disease states such as
      atherosclerosis, OSA and sepsis, but as yet its potential effects on CBF during
      sleep or OSA is unknown. We aimed to produce a novel animal model of coronary
      artery endothelial dysfunction, subsequently to be used to study the role of the
      endothelium in regulating CBF during OSA. METHODS: Lambs (n=6) were instrumented
      under general anaesthesia (2% Halothane, 50% O2, balance N2O) for recording CBF
      (Transonic flow probe around circumflex coronary artery), central arterial blood
      pressure (Pca), central venous pressure (Pjv) and sleep monitoring (bio
      electrodes). Coronary vascular resistance (CVR) was calculated as (Pca-Pjv)/CBF.
      Following>or=72 h of recovery, endothelial damage was induced by infusing
      lipopolysaccharide (LPS, 2 microg/kg over 30 min) on 3 successive days. The day
      before and the day after the period of LPS infusion, sleep studies were performed
      and coronary artery endothelial function was assessed by comparing CBF and CVR
      responses to left atrial injection of endothelial-dependent (Acetylcholine [Ach])
      and independent (sodium nitroprusside [SNP]) vasodilators. RESULTS: Prior to LPS,
      arterial blood pressure was lower in tonic active sleep (AS) and higher in phasic
      AS than wakefulness. CBF and arterial blood pressure were slightly higher in
      phasic AS compared to tonic AS, and were the same in quiet sleep compared to
      quiet wakefulness. CVR did not differ across sleep states. After LPS, systolic
      blood pressure was reduced compared to before LPS in all sleep states, while
      other parameters were unchanged. Prior to LPS treatment, increasing doses of Ach
      (0.0001-1.0 microg/kg) and SNP (0.45-4.5 microg/kg) led to progressive reductions
      in CVR and increases in CBF. After LPS treatment, the fall in CVR and increase in
      CBF in response to Ach was attenuated (two-way repeated measures analysis of
      variance (ANOVA), P<0.05), whereas it was unchanged in response to SNP.
      CONCLUSION: LPS leads to impaired coronary artery vasodilation in response to
      endothelial-dependent, but not endothelial-independent vasodilators. This novel
      model of coronary artery endothelial dysfunction in the sleeping lamb will
      provide the opportunity to study the regulation of CBF during OSA.

PMID- 16996309
TI  - Stress-related sleep disturbance and polysomnographic response to caffeine.
AB  - BACKGROUND AND PURPOSE: To determine the sleep response to caffeine in
      individuals vulnerable to stress-related sleep disturbance as measured by
      polysomnography. PATIENTS AND METHODS: Eleven healthy individuals without
      insomnia scoring low (4 women, mean age=32.64+/-15.46 years) and 10 healthy
      individuals also without insomnia scoring high (6 women, mean age=34.20+/-13.73
      years) on a measure of vulnerability to stress-related sleep disturbance were
      studied in a laboratory protocol. A moderate-low dose of caffeine (3 mg/kg) was
      administered 1h prior to lights-out and compared to a counterbalanced control
      night with each condition separated by 1 week. Standard polysomnographic measures
      were assessed (i.e. total sleep time, sleep efficiency, latency to persistent
      sleep, and sleep stage percentages) for both control and caffeine nights.
      RESULTS: There were no between-group differences in sleep on the control night.
      Importantly, individuals reporting vulnerability to stress-related sleep
      disturbance had significantly prolonged latency to persistent sleep in response
      to the caffeine challenge (interaction; P<0.05). CONCLUSION: Normal sleepers with
      an identified vulnerability to stress-induced sleep disturbance exhibited greater
      objectively verifiable sleep-reactivity in response to a caffeine challenge
      compared to non-vulnerable individuals. These results suggest that the construct
      of individual differences in vulnerability to sleep disturbance applies to a
      pharmacological 'stressor' (i.e. caffeine) as well as to previously assessed
      stressors such as a first-night effect. This finding provides further support for
      generalized trait vulnerability by demonstrating a sleep disturbance to a wake
      promoting pharmacological challenge in specific a priori identified individuals.

PMID- 16996310
TI  - Test-to-test variability in motor activity during the suggested immobilization
      test in restless legs patients.
AB  - BACKGROUND AND PURPOSE: To evaluate the test-to-test variability of the suggested
      immobilization test (SIT) in patients with restless legs syndrome (RLS). PATIENTS
      AND METHODS: Twenty patients with primary RLS (12 men and eight women; age:
      53.3+/-11.3 years) were selected for the study. We compared the results of two
      SITs performed on two consecutive evenings prior to polysomnographic recordings.
      RESULTS: Overall, the periodic leg movement index during the SIT (SIT PLM) and
      the SIT PLM index associated with sensory manifestations (SIT PLM+) were not
      significantly different between tests. The number of PLM sequences per SIT, the
      mean PLM duration and the PLM interval did not significantly change between the
      two consecutive tests. The pattern of temporal evolution of motor activity across
      the SIT was very reproducible, SIT PLM showing a clear tendency to a progressive
      increase across the test, with the SIT PLM+ index decreasing in the second half
      of the test. Despite good reproducibility, there were marked intra-individual
      differences. Considering the proposed cut-off value of 12 for the SIT PLM index
      to confirm RLS, 11 patients were positive at the first test and four additional
      patients became positive at the second test. SIT PLM index changes did not
      correlate with age, severity of disease and polysomnographic measures.
      CONCLUSIONS: Quantitative analysis of motor activity during two consecutive SITs
      in RLS patients showed a significant inter-test intra-individual variability
      unrelated to demographic, clinical or polysomnographic parameters. SIT PLM index
      variability suggests that a single test would not be sensitive enough for
      diagnostic purposes in unclear cases and that new criteria need to be applied to
      increase its specificity and sensitivity.

PMID- 16996311
TI  - Is psychiatric illness a comorbidity or a contributing cause to RLS?

PMID- 16996312
TI  - Is iliotibial band syndrome really a friction syndrome?
AB  - Iliotibial band (ITB) syndrome is regarded as an overuse injury, common in
      runners and cyclists. It is believed to be associated with excessive friction
      between the tract and the lateral femoral epicondyle-friction which 'inflames'
      the tract or a bursa. This article highlights evidence which challenges these
      views. Basic anatomical principles of the ITB have been overlooked: (a) it is not
      a discrete structure, but a thickened part of the fascia lata which envelops the
      thigh, (b) it is connected to the linea aspera by an intermuscular septum and to
      the supracondylar region of the femur (including the epicondyle) by coarse,
      fibrous bands (which are not pathological adhesions) that are clearly visible by
      dissection or MRI and (c) a bursa is rarely present-but may be mistaken for the
      lateral recess of the knee. We would thus suggest that the ITB cannot create
      frictional forces by moving forwards and backwards over the epicondyle during
      flexion and extension of the knee. The perception of movement of the ITB across
      the epicondyle is an illusion because of changing tension in its anterior and
      posterior fibres. Nevertheless, slight medial-lateral movement is possible and we
      propose that ITB syndrome is caused by increased compression of a highly
      vascularised and innervated layer of fat and loose connective tissue that
      separates the ITB from the epicondyle. Our view is that ITB syndrome is related
      to impaired function of the hip musculature and that its resolution can only be
      properly achieved when the biomechanics of hip muscle function are properly
      addressed.

PMID- 16996313
TI  - Involvement of some large immunophilins and their ligands in the protection and
      regeneration of neurons: a hypothetical mode of action.
AB  - The powerful immunosuppressive drugs such as FK506 and its derivatives induce
      some regeneration and protection of neurons from ischaemic brain injury and some
      other neurological disorders. The drugs form complexes with diverse FKBPs but
      apparently the FKBP52/FK506 complex was shown to be involved in the protection
      and regeneration of neurons. We used several different sequence attributes in
      searching diverse genomic databases for similar motifs as those present in the
      FKBPs. A Fortran library of algorithms (Par_Seq) has been designed and used in
      searching for the similarity of sequence motifs extracted from the multiple
      sequence alignments of diverse groups of proteins (query motifs) and the target
      motifs which are encoded in various genomes. The following sequence attributes
      were used in the establishment of the degree of convergence between: (A) amino
      acid (AA) sequence similarity (ID) of the query/target motifs and (B) their: (1)
      AA composition (AAC); (2) hydrophobicity (HI); (3) Jensen-Shannon entropy; and
      (4) AA propensity to form a particular secondary structure. The sequence hallmark
      of two different groups of peptidylprolyl cis/trans isomerases (PPIases), namely
      tetratricopetide repeat (TPR) motifs, which are present in the heat-shock
      cyclophilins and in the large FK506-binding proteins (FKBPs) were used to search
      various genomic databases. The Par_Seq algorithm has revealed that the TPR motifs
      have similar sequence attributes as a number of hydrophobic sequence segments of
      functionally unrelated membrane proteins, including some of the TMs from diverse
      G protein-coupled receptors (GPCRs). It is proposed that binding of the
      FKBP52/FK506 complex to the membranes via the TPR motifs and its interaction with
      some membrane proteins could be in part responsible for some neuro-regeneration
      and neuro-protection of the brain during some ischaemia-induced stresses.

PMID- 16996315
TI  - Effect of early administration of the N-methyl-d-aspartate receptor antagonist
      amantadine on the development of postmastectomy pain syndrome: a prospective
      pilot study.
AB  - Postmastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that might
      develop after breast surgery. Like many other forms of neuropathic pain, it is
      relatively resistant to treatment and negatively affects the quality of life. A
      double-blind, randomized, placebo-controlled pilot trial was conducted to study
      the analgesic efficacy of perioperative administration of the N-methyl-D
      aspatrate (NMDA) receptor antagonist amantadine in preventing PMPS after
      mastectomy plus axillary lymph node dissection (ALND). In the study group, a
      regimen of 200 mg/day of amantadine was started 1 day before surgery and
      continued for 14 days, whereas the control group received a placebo. Patients
      were required to indicate the exact location of their pain and to record its
      level at 1, 3, and 6 months after surgery. Neurologic examination and
      Quantitative Thermal Testing (QTT) were performed 1 and 6 months after surgery.
      On both the neurologic examination and the QTT, all patients, regardless of the
      perioperative intervention (amantadine or placebo), presented evidence for nerve
      injury, manifested primarily by painful hypoesthesia (anesthesia dolorosa) in the
      axilla or inner arm. PMPS persisted for the entire duration of the study in 82%
      of the patients who were available for follow-up. The average intensity of the
      pain was moderate in both groups and tended not to decline over time. No
      differences between the 2 groups in any of the outcome parameters reached
      statistical significance. According to the results of the present pilot study,
      the NMDA antagonist amantadine does not prevent the development of PMPS in
      patients who undergo breast surgery with ALND. PERSPECTIVE: Breast surgery that
      involves ALND seems to uniformly cause nerve injury, which cannot be prevented by
      the perioperative administration of 200 mg of amantadine. It is most commonly
      presented by painful hypoesthesia or anesthesia dolorosa in the axillary/inner
      arm area, which is moderate in intensity and likely to persist for at least 6
      months.

PMID- 16996316
TI  - Biomedical knowledge navigation by literature clustering.
AB  - There is an urgent need for a system that facilitates surveys by biomedical
      researchers and the subsequent formulation of hypotheses based on the knowledge
      stored in literature. One approach is to cluster papers discussing a topic of
      interest and reveal its sub-topics that allow researchers to acquire an overview
      of the topic. We developed such a system called McSyBi. It accepts a set of
      citation data retrieved with PubMed and hierarchically and non-hierarchically
      clusters them based on the titles and the abstracts using statistical and natural
      language processing methods. A novel point is that McSyBi allows its users to
      change the clustering by entering a MeSH term or UMLS Semantic Type, and
      therefore they can see a set of citation data from multiple aspects. We evaluated
      McSyBi quantitatively and qualitatively: clustering of 27 sets of citation data
      (40643 different papers) and scrutiny of several resultant clusters. While non
      hierarchical clustering provides us with an overview of the target topic,
      hierarchical clustering allows us to see more details and relationships among
      citation data. McSyBi is freely available at http://textlens.hgc.jp/McSyBi/.

PMID- 16996314
TI  - Cyclophosphamide increases transgene expression mediated by an oncolytic
      adenovirus in glioma-bearing mice monitored by bioluminescence imaging.
AB  - Approaches to improve the oncolytic potency of replication-competent adenoviruses
      include the insertion of therapeutic transgenes into the viral genome. Little is
      known about the levels and duration of in vivo transgene expression by cells
      infected with such "armed" viruses. Using a tumor-selective adenovirus encoding
      firefly luciferase (AdDelta24CMV-Luc) we investigated these questions in an
      intracranial mouse model for malignant glioma. Luciferase expression was detected
      by bioluminescence imaging, and the effect of the immunosuppressive agent
      cyclophosphamide (CPA) on transgene expression was assessed. Intratumoral
      AdDelta24CMV-Luc injection led to a localized dose-dependent expression of
      luciferase. Surprisingly, this expression decreased rapidly during the course of
      14 days. In contrast, mice injected with nonreplicating Ad.CMV-Luc demonstrated
      stable transgene expression. Treatment of mice with CPA in combination with
      AdDelta24CMV-Luc retarded the loss of transgene expression. Staining of mouse
      brains for inflammatory cells demonstrated decreased tumor infiltration by immune
      cells in CPA-treated mice. Moreover, in immunodeficient NOD/SCID mice loss of
      transgene expression was less rapid and not prevented by CPA treatment. Together,
      our data demonstrate that transgene expression and viral replication decrease
      rapidly after intratumoral injection of oncolytic adenovirus in mouse brains and
      that treatment with the immunomodulator CPA prolongs viral-mediated gene
      expression.

PMID- 16996317
TI  - Gene therapy for vascular disease.
AB  - It is now feasible to transfer genes to blood vessels to alter vascular function.
      An alternative approach is to transfer genes to liver or skeletal muscle, so that
      the transgene releases a protein into blood, and the protein binds to blood
      vessels to alter vascular function. Gene therapy is being tested for treatment of
      diseases, such as ischemia in patient with peripheral vascular disease, which
      cannot be treated with medications. Common diseases, such as hypertension and
      hypercholesterolemia, also may be targets for gene therapy. Periodic intravenous
      injection of a vector for gene transfer has the potential for circumventing poor
      compliance in taking daily medications for these diseases. The key obstacle to
      widespread use of gene therapy is that a safe and efficient vector for delivery
      of genes has not yet been developed.

PMID- 16996318
TI  - Impact of bariatric surgery on cardiovascular and musculoskeletal morbidity.
AB  - BACKGROUND: Obesity is currently recognized as a global epidemic. According to
      recent statistics, the prevalence of obesity increased from 13.8% of the Canadian
      population in 1978-1979 to 23.1% in 2004, and the prevalence of morbid obesity
      increased from .9% in 1978-1979 to 2.7% in 2004. Obesity is a known risk factor
      for highly prevalent chronic diseases, including cardiovascular and
      musculoskeletal disorders. The objective of the study was to assess the impact of
      bariatric surgery on cardiovascular and musculoskeletal morbidity. METHODS: This
      was an observational study that compared a cohort of 1035 morbidly obese patients
      treated with bariatric surgery at the Centre for Bariatric Surgery, McGill
      University Health Centre with a matched cohort of 5746 morbidly obese
      nonsurgically treated controls. Data were obtained from the Quebec provincial
      health insurance database (Regie de l'Assurance Maladie du Quebec). Morbidity
      indicators included diagnoses or treatment for cardiovascular or musculoskeletal
      disorders. RESULTS: Patients who underwent bariatric surgery had a significant
      62% mean reduction in excess weight and 32% mean reduction in body mass index (P
      < .001). Compared with the matched controls, patients who had undergone bariatric
      surgery had significantly lower rates of diagnoses and treatments related to
      cardiovascular and musculoskeletal conditions. CONCLUSIONS: These results
      indicate that bariatric surgery is effective in reducing weight and significantly
      reduces the risk of cardiovascular and musculoskeletal morbidity.

PMID- 16996319
TI  - Obesity disease burden and surgical risk.
AB  - BACKGROUND: The rapid national expansion in bariatric surgical procedures has
      been accompanied by recent reports of significant complication rates. This has
      resulted in increased public scrutiny of bariatric surgery outcomes, restrictions
      on patient eligibility criteria by payors, and credentialing requirements for
      providers. This focus on outcomes has resulted in interest in bariatric risk
      analysis. METHODS: During an 8-year period, 1210 patients were evaluated for
      bariatric surgery. Clinical information was recorded prospectively. Co-morbid
      medical conditions were analyzed according to proven surgical risk factors: age,
      body mass index (BMI), and male gender. RESULTS: The prevalence of many co-morbid
      conditions and the total number of co-morbid conditions correlate highly with
      increasing age, increasing BMI, and male gender. CONCLUSION: The established
      surgical risk factors, age, BMI, and male gender, are markers for a sicker
      patient population, as evidenced by a greater obesity disease burden.

PMID- 16996320
TI  - Recruitment issues when primary care population clusters are used in randomised
      controlled clinical trials: climbing mountains or pushing boulders uphill?
AB  - Cluster randomised controlled trials for health promotion, education, public
      health or organisational change interventions are becoming increasingly common to
      inform evidence-based policy. However, there is little published methodological
      evidence on recruitment strategies for primary care population clusters. In this
      paper, we discuss how choosing which population cluster to randomise can impact
      on the practicalities of recruitment in primary care. We describe strategies
      developed through our experiences of recruiting primary care organisations to
      participate in a national randomised controlled trial of a policy to provide
      community breastfeeding groups for pregnant and breastfeeding mothers, the BIG
      (Breastfeeding in Groups) trial. We propose an iterative qualitative approach to
      recruitment; collecting data generated through the recruitment process,
      identifying themes and using the constant comparative method of analysis. This
      can assist in developing successful recruitment strategies and contrasts with the
      standardised approach commonly used when recruiting individuals to participate in
      randomised controlled trials. Recruiting primary care population clusters to
      participate in trials is currently an uphill battle in Britain. It is a complex
      process, which can benefit from applying qualitative methods to inform trial
      design and recruitment strategy. Recruitment could be facilitated if health
      service managers were committed to supporting peer reviewed, funded and ethics
      committee approved research at national level.

PMID- 16996321
TI  - Effects of human pregnancy and advancing gestation on respiratory discomfort
      during exercise.
AB  - This study examined the effects of human pregnancy and advancing gestation on the
      intensity of respiratory discomfort (dyspnea) during cycle exercise. Fourteen
      pregnant women (PG) performed a progressive cycle ergometer exercise test
      involving 20 W/min increases in work rate to symptom limitation and/or a heart
      rate of 170-175 beats/min at 19.7+/-1.2 weeks (ENTRY), 28.2+/-0.3 weeks (TM2) and
      36.3+/-0.3 weeks (TM3) gestation. Eight, age-matched, sedentary non-pregnant
      women (CG) were also studied for comparison purposes. Measurements included
      dyspnea intensity (Borg scale), minute ventilation (VE), breathing pattern and
      other cardiorespiratory parameters. At peak exercise, neither pregnancy nor
      advancing gestation had an effect on dyspnea, VE, breathing pattern, oxygen
      uptake or work rate (p>0.05). VE was significantly greater (by 11 L/min at 100 W)
      in the PG at TM3 versus CG (p<0.05) at all submaximal work rates. VE also
      increased progressively from ENTRY to TM2 and TM3 during submaximal exercise.
      Dyspnea was not significantly different at any submaximal work rate in the PG at
      TM3 versus CG or with advancing gestation in the PG. In addition, dyspnea at a
      standardized exercise VE of 40 L/min was not different at TM3 versus ENTRY or in
      the PG at TM3 versus CG. Neither pregnancy nor advancing gestation were
      associated with increased respiratory discomfort during strenuous non-weight
      bearing cycle ergometer exercise, despite substantial increases in VE and
      progressive mechanical adaptations of the respiratory system to accommodate the
      increasing size of the gravid uterus.

PMID- 16996322
TI  - Effects of inspiratory muscle training on exercise responses in normoxia and
      hypoxia.
AB  - The purpose of this study was to determine the effects of inspiratory muscle
      training (IMT) on exercise in hypoxia (H) and normoxia (N). A 4-week IMT program
      was implemented with 12 healthy subjects using an inspiratory muscle trainer set
      at either 15% (C; n=5) or 50% (IMT; n=7) maximal inspiratory mouth pressure
      (PImax). Two treadmill tests (85% VO2max) to exhaustion and measures of diaphragm
      thickness (Tdi) and function were completed before and after training in H and N.
      Significant increases of 8-12% and 24.5+/-3.1% in Tdi and PImax, respectively,
      were seen in the IMT group. Time to exhaustion remained unchanged in all
      conditions. Inspiratory muscle fatigue (downward arrowPImax) following exercise
      was reduced approximately 10% (P<0.05) in IMT after both N and H. During H, IMT
      reduced (P<0.05) VO2 by 8-12%, cardiac output by 14+/-2%, ventilation by 25+/-3%;
      and increased arterial oxygen saturation by 4+/-1% and lung diffusing capacity by
      22+/-3%. Ratings of perceived exertion and dyspnea were also significantly
      reduced. These data suggest that IMT significantly improves structural and
      functional physiologic measures in hypoxic exercise.

PMID- 16996323
TI  - Chemometric analysis of retention data from salting-out thin-layer chromatography
      in relation to structural parameters and biological activity of chosen
      sulphonamides.
AB  - Salting-out thin-layer chromatography of several chosen sulphonamides on silica
      gel has been examined with aqueous solutions of salts: sulphates, chlorides,
      nitrates, phosphates, acetates, thiocyanates. It was established that applied
      salts have different effects on retention of sulphonamides accordingly to
      Hofmeister's clasification (e.g. kosmotropes, chaotropes and neutral). The
      parameters of the linear regression analysis of dependences between the R(M)
      values and concentration of the salt in the eluent system were correlated with
      QSAR ones. It appeared that chromatographic parameters obtained by SOTLC method
      reflect not only physico-chemical properties of examined compounds but also they
      include information about their activity. 3D graph revealing pharmacological
      properties of analytes was constructed. Universal character of this method for
      predicting and classification of drug containing sulphonamide group was confirmed
      by localisation of additional compounds structurally similar but acting
      antagonistically towards sulphonamides.

PMID- 16996324
TI  - Membrane adsorbers as purification tools for monoclonal antibody purification.
AB  - Downstream purification processes for monoclonal antibody production typically
      involve multiple steps; some of them are conventionally performed by bead-based
      column chromatography. Affinity chromatography with Protein A is the most
      selective method for protein purification and is conventionally used for the
      initial capturing step to facilitate rapid volume reduction as well as separation
      of the antibody. However, conventional affinity chromatography has some
      limitations that are inherent with the method, it exhibits slow intraparticle
      diffusion and high pressure drop within the column. Membrane-based separation
      processes can be used in order to overcome these mass transfer limitations. The
      ligand is immobilized in the membrane pores and the convective flow brings the
      solute molecules very close to the ligand and hence minimizes the diffusional
      limitations associated with the beads. Nonetheless, the adoption of this
      technology has been slow because membrane chromatography has been limited by a
      lower binding capacity than that of conventional columns, even though the high
      flux advantages provided by membrane adsorbers would lead to higher productivity.
      This review considers the use of membrane adsorbers as an alternative technology
      for capture and polishing steps for the purification of monoclonal antibodies.
      Promising industrial applications as well as new trends in research will be
      addressed.

PMID- 16996325
TI  - Determination of eflornithine enantiomers in plasma, by solid-phase extraction
      and liquid chromatography with evaporative light-scattering detection.
AB  - A bioanalytical method for determination of eflornithine (DFMO) in 1000 microL
      human plasma has been developed and validated. DFMO and the internal standard
      (IS) were analysed by liquid chromatography with evaporative light-scattering
      detection (ELSD). Separation was performed on a Chirobiotic TAG (250 mm x 4.6 mm)
      column with ethanol (99.5%):0.01 mol/L acetic acid-triethylamine buffer at the
      rate of 25:75% (v/v) with flow rate of 1.0 mL/min. For d-DFMO in plasma the inter
      assay precision was 6.5% at 75 micromol/L, 6.6% at 375 micromol/L and 5.8% at 750
      micromol/L. For l-DFMO in plasma the inter-assay precision was 10.4% at 75
      micromol/L, 6.5% at 375 micromol/L and 5.0% at 750 micromol/L. The lower limit of
      quantification (LLOQ) was determined to 25 micromol/L where the precision was
      4.3% and 5.7%, respectively.

PMID- 16996326
TI  - Mexican body mass index values in the late-19th-century American West.
AB  - No research has been done on the body mass index values of the 19th-century
      Mexican population. This paper introduces a new data source of 19th-century
      Mexican male inmates in American prisons and finds that the majority of Mexican
      body mass was in the normal range (18.5-24.9). Few Mexicans were underweight or
      obese by modern standards. Body mass varied little (0-0.9 units) by occupations
      possibly because criminals probably came from the lower end of the socioeconomic
      distribution; however, it did vary with crimes for which inmates were
      incarcerated.

PMID- 16996327
TI  - Seasonal anthropometric cycles in a command economy: the case of Czechoslovakia,
      1946-1966.
AB  - Anthropometric evidence is used to shed light on the living standards in early
      communist Czechoslovakia (1946-1966). Height and weight variation of adolescent
      boys exhibit a pattern that is inconsistent with that for a normal healthy
      population. The hypothesis is proposed that this pattern arose from periodic food
      supply shortages, most marked in the spring of each year. The boys in the sample
      display a remarkably slow growth during the spring but catch up over the summer.

PMID- 16996328
TI  - High prevalence of coeliac disease: need for increasing awareness among
      physicians.
AB  - BACKGROUND: Coeliac disease is a wheat gluten and related prolamines-induced
      disease with a prevalence that may be underestimated in many geographical regions
      and populations. AIM: To investigate the prevalence of coeliac disease in a
      population of schoolchildren of Estonia using tissue transglutaminase antibodies
      for screening. SUBJECTS AND METHODS: The study was designed as cross-sectional.
      Serum samples from 1160 randomly selected schoolchildren (636 female and 564
      male, aged 9 or 15 years) were studied using a novel tissue transglutaminase
      antibody immunoassay (EliA Celikey IgA assay). Antibody-positive subjects were
      investigated for coeliac disease. RESULTS: A total of five subjects had
      antibodies. Four of them agreed for further investigations. By small-bowel biopsy
      they all were confirmed to have active coeliac disease, including three subjects
      with symptoms that were not considered by their family doctors. The prevalence of
      coeliac disease is at least 1 case per 290 (0.34% with CI 0.09-0.88%) in Estonia.
      It is much higher than that in our previous screening studies but is comparable
      with data from other European countries. CONCLUSION: The prevalence of coeliac
      disease might have increased during the last decade in Estonia. This study
      clearly shows that the awareness of coeliac disease among physicians is low.
      Thus, there is a need for more epidemiological studies and education related to
      coeliac disease.

PMID- 16996329
TI  - Clinical characteristics of synchronous colorectal cancer are different according
      to tumour location.
AB  - AIMS: The purpose of this study was to investigate the clinical characteristics
      of synchronous cancer patients, with particular attention given to variations in
      tumour location. METHODS: A retrospective evaluation of 249 synchronous cancer
      cases out of 3061 consecutive colorectal cancer patients. RESULTS: Multivariate
      analysis of risk factors for synchronous cancer according to tumour location
      revealed that male gender was a significant risk for synchronous lesions in the
      left colon only (odds ratio=2.05, 95% confidence interval 1.34-3.13). Meanwhile,
      aging was a risk factor for synchronous cancer in the right colon only (odds
      ratio=1.05, 95% confidence interval 1.02-1.08), and in both sides of the colon
      (odds ratio=1.03, 95% confidence interval 1.01-1.05), but not in the left colon
      only (odds ratio=0.98, 95% confidence interval 0.97-1.00). In addition, patients
      with synchronous lesions in the right colon only tended to have adenomas in the
      right colon, while those with synchronous lesions in the left colon only tended
      to have adenomas in the left colon (each P value <0.05). CONCLUSION: The risk
      factors and status of concurrent adenomas of synchronous cancer cases varied
      according to tumour location, suggesting that the colonic site susceptible to
      neoplasia varies according to patient characteristics.

PMID- 16996330
TI  - Analysis of risk factors for early hepatic artery thrombosis after liver
      transplantation. Possible contribution of reperfusion in the early morning.
AB  - BACKGROUND: Since the incidence of myocardial infarction and other cardiovascular
      ischaemic events is highest in early morning, on account of a relative
      hypercoagulable state occurring in this time period, an attempt was made to test
      whether reperfusion of the hepatic artery at this time of the day, at liver
      transplantation, produces an increased risk of early thrombosis. METHODS: The
      records of 255 consecutive patients receiving a first transplant for chronic
      liver disease were retrospectively analysed. As possible risk factors, for early
      post-operative thrombosis (<30 days from transplantation), several medical and
      surgical parameters were taken into consideration. Arterial reperfusion was
      considered to have taken place at a time of high coagulability when occurred
      between 6.00 a.m. and 10.00 a.m. on the basis of previous reports. RESULTS:
      Logistic regression identified donor age (OR for age >60: P=0.017), bench
      reconstruction of the artery (OR: 5.06, P=0.013) and time of high coagulability
      at reperfusion (OR 2.93, P=0.087), as independently associated with early hepatic
      artery thrombosis. CONCLUSIONS: The present findings identified three independent
      predictors of early hepatic thrombosis, warranting stricter post-surgical follow
      up of patients presenting such conditions. Interestingly, these factors are
      consistent with arterial reperfusion in the early morning being associated with
      an increased risk of early hepatic artery thrombosis, suggesting relative
      coagulative imbalances to provide a contribution in the pathogenesis of this
      severe complication of liver transplantation.

PMID- 16996331
TI  - Microhardness of starch based biomaterials in simulated physiological conditions.
AB  - In this work the variation of the surface mechanical properties of starch-based
      biomaterials with immersion time was followed using microhardness measurements.
      Two blends with very distinct water uptake capabilities, starch/cellulose acetate
      (SCA) and starch/poly(epsilon-caprolactone) (SPCL), were immersed in a phosphate
      buffer solution (PBS) at 37.5 degrees C for various times. The microhardness of
      the blends decreased significantly ( approximately 50% for SPCL and approximately
      94% for SCA), within a time period of 30 days of immersion, reflecting the
      different hydrophilic character of the synthetic components of the blends. The
      dependence of microhardness on the applied loading time and load was also
      analysed and showed a power law dependency for SCA. Water uptake and weight loss
      measurements were performed for the same immersion times used in the
      microhardness experiments. The different swelling/degradation behaviour presented
      by the blends was related to the respective variation in microhardness. Moreover,
      complementary characterization of the mechanical properties of SCA and SPCL was
      accomplished by dynamic mechanical analysis (DMA) and creep measurements.
      Microhardness measurements proved to be a useful technique for characterizing the
      mechanical behaviour near the surface of polymeric biomaterials, including in
      simulated physiological conditions.

PMID- 16996332
TI  - Risk management considerations and the pregnancy handheld record. An audit of the
      return rate of the pregnancy handheld record.
AB  - PURPOSE: Risk management is integral to the provision of contemporary health
      care. As maternity practices change and with a commitment on women being at the
      centre of care, one strategy has been for women to retain their records during
      the antenatal period. This paper explores the return rate of the pregnancy
      handheld record in a major tertiary facility and discusses the risk management
      implications when the record is not available upon presentation to the treating
      practitioner. PROCEDURE: Four audits were conducted over a 2 year period to
      determine the return rate of the pregnancy handheld record at time of admission
      for labour and birth. A total of 1096 records were returned out of a possible
      1256 during the study. FINDINGS: A 6.6% increase in the return rate was achieved
      over the 4 audit periods (82-88.5%) with an overall return rate of 85%. PRINCIPLE
      CONCLUSIONS: Our audit highlights the need for consumers, clinicians and heath
      care facilities to consider the advantages and disadvantages of the pregnancy
      handheld record, as well as the medico-legal responsibilities that ultimately
      fall back on the health facility.

PMID- 16996333
TI  - Effects of ibandronate on bone quality: preclinical studies.
AB  - Osteoporosis is a skeletal disorder characterized by low bone mass and
      deterioration of bone microarchitecture resulting in bone fragility, which
      increases the risk of fracture. The clinical efficacy of bisphosphonates is
      evaluated through improvements in bone mineral density (BMD) and reductions in
      the risk for fracture. However, as bisphosphonates are administered long term,
      there is increasing interest in their effects on bone quality, which includes
      bone mass, strength and architecture. Ibandronate is a potent, nitrogen
      containing bisphosphonate with significant antifracture efficacy when
      administered daily and in regimens with extended between-dose intervals. Clinical
      studies with ibandronate are supported by an extensive preclinical program that
      investigated the efficacy and bone safety of ibandronate in various animal models
      of osteoporosis. In preclinical studies, treatment with ibandronate maintained,
      or improved the quality, strength and architecture of bone. Intermittent and
      daily ibandronate regimens provided similar benefits. During ibandronate
      treatment, the bone retains its capacity for repair and bone mineralization is
      not adversely affected. Notably, positive relationships among BMD, bone strength
      and bone architecture have been demonstrated. This review describes the
      preclinical evidence for the preservation of bone quality with ibandronate,
      irrespective of the dosing regimen and even when administered at doses higher
      than those used therapeutically.

PMID- 16996334
TI  - Clinical presentation of patients with eosinophilic inflammation of the
      esophagus.
AB  - BACKGROUND: Allergic eosinophilic esophagitis (AEE) is defined by a dense
      infiltrate of eosinophils within the esophageal mucosa and the absence of
      pathological gastroesophageal reflux. OBJECTIVE: To characterize a pediatric
      population with AEE to determine if AEE can be diagnosed based on history; to
      compare patients with varying degrees of esophageal eosinophilic inflammation to
      determine if moderate esophageal inflammation is part of a continuum of AEE.
      DESIGN: Medical records of 112 patients with eosinophils on esophageal biopsy
      specimens were reviewed. Patients were grouped according to eosinophils per high
      power field (eos/hpf): group 1 (1-5 eos/hpf, n = 31), group 2 (6-14 eos/hpf, n =
      13), and group 3 (> or =15 eos/hpf, n = 68) and compared. SETTING: University
      Children's Hospital. PATIENTS: Children and adolescents with eosinophils on
      esophageal mucosal biopsy specimens. INTERVENTIONS: Analysis of clinical
      information. MAIN OUTCOME MEASUREMENTS: Clinical characterization of patients
      with esophageal eosinophilia. RESULTS: There was no significant difference in
      patient demographics. Patients in groups 2 and 3 had multiple food allergens
      identified. Patients in group 3 with a positive type I allergic response were
      significantly younger than those with a negative response (mean, 4.6 years old vs
      mean, 8.5 years old; P = .0065). In group 2, 3 of 13 patients responded
      histologically to acid-suppressive therapy, whereas 6 patients had improved
      histology with corticosteroids; 4 of these 6 patients had not responded
      histologically to acid-suppression. LIMITATIONS: Retrospective study.
      CONCLUSIONS: History and clinical presentation were not useful in predicting the
      severity of histologic esophageal inflammation in this cohort. Patients with
      moderate esophageal eosinophilia (group 2) exhibited a variable response to
      medical therapy.

PMID- 16996335
TI  - Undernutrition is predictive of early mortality after palliative self-expanding
      metal stent insertion in patients with inoperable or recurrent esophageal cancer.
AB  - BACKGROUND: Self-expanding metallic stents (SEMS) are a first-line therapeutic
      procedure in the palliative treatment of dysphagia in patients with esophageal
      cancer. However, the impact of SEMS insertion on patient nutritional status has
      never been assessed. OBJECTIVE: To evaluate the nutritional status of patients
      after insertion of a SEMS and the impact of a preexisting undernutrition status
      on survival. DESIGN: Retrospective observational study. PATIENTS: A total of 120
      patients treated in a single center by insertion of a SEMS for relief of
      dysphagia in the palliative treatment of esophageal cancer were retrospectively
      included. MAIN OUTCOME MEASUREMENTS: Efficacy of SEMS was assessed by the
      Ogilvie's dysphagia score. Patient nutritional and clinical statuses were
      evaluated at SEMS insertion, and patients were regularly followed until death.
      Independent predictive factors of early 30-day mortality were researched.
      RESULTS: Dysphagia scores decreased after SEMS insertion in 89.1% of patients,
      with median scores decreasing from 3.0 to 1.0 (P < .05). There was a significant
      decrease in body mass index (BMI) (P < .04), serum albumin level (P < .01), and
      World Health Organization (WHO) performance index (P < .02) at a 1-month
      evaluation. Serum albumin level, BMI <18 kg/m(2), and WHO performance index >2 at
      SEMS insertion were independent predictive factors of 30-day mortality.
      CONCLUSIONS: This study suggested that palliative stent placement in esophageal
      cancer was effective to relieve dysphagia but was not followed by an improvement
      of nutritional parameters. Moreover, it underlined the key role played by
      undernutrition on survival.

PMID- 16996336
TI  - Endoscopic management of foreign bodies in the upper-GI tract: experience with
      1088 cases in China.
AB  - BACKGROUND: Reports on endoscopic management of ingested foreign bodies of the
      upper-GI tract in China are scarce. OBJECTIVE: To report our experience and
      outcome in the management of ingestion of foreign bodies in Chinese patients.
      SETTING AND PATIENTS: Between January 1980 and January 2005, a total of 1088
      patients (685 men and 403 women; age range, 1 day to 96 years old) with suspected
      foreign bodies were admitted to our endoscopy center. INTERVENTIONS: All patients
      underwent endoscopic procedure after admission. MAIN OUTCOME MEASUREMENTS:
      Demographic and endoscopic data, including age, sex, and referral sources of
      patients, types, number and location of foreign bodies, associated upper-GI
      diseases, endoscopic methods, and accessory devices for removal of foreign bodies
      were collected and analyzed. RESULTS: A total of 1090 foreign bodies were found
      in 988 (90.8%) patients. The types of foreign bodies varied greatly: mainly food
      boluses, coins, fish bones, dental prostheses, or chicken bones. The foreign
      bodies were located in the pharynx (n = 12), the esophagus (n = 577), the stomach
      (n = 441), the duodenum (n = 50), and the surgical anastomosis (n = 10). The
      associated GI diseases (n = 88) included esophageal carcinoma (33.0%), stricture
      (23.9%), diverticulum (15.9%), postgastrectomy (11.4%), hiatal hernia (10.2%),
      and achalasia (5.7%). A rat-tooth forceps and a snare were the most frequently
      used accessory devices. The success rate for foreign-body removal was 94.1%
      (930/988). CONCLUSIONS: Ingestion of foreign bodies is a common clinic problem in
      China. Endoscopy procedures are frequently performed, and a high proportion of
      patients with foreign bodies require endoscopic intervention.

PMID- 16996337
TI  - Fast-food bolus nation.

PMID- 16996338
TI  - EUS staging of upper GI malignancies: results of a prospective randomized trial.
AB  - BACKGROUND: Electronic 270 degrees transverse-array EUS (TA-EUS) provides high
      quality cross-sectional images but cannot guide FNA. Linear EUS (L-EUS) provides
      longitudinal images of malignancies and the ability to guide FNA. OBJECTIVE: We
      conducted a prospective randomized comparison of TA-EUS and L-EUS for the staging
      of upper-GI (UGI) malignancies. DESIGN: Forty-three patients underwent L-EUS
      immediately followed by TA-EUS (N = 27, 63%) or TA-EUS immediately followed by L
      EUS (N = 16, 37%). PATIENTS: Forty-three subjects (mean age, 64 years; 37 men)
      with an UGI malignancy (4 stomach and 38 esophageal) were evaluated with both TA
      EUS and L-EUS. INTERVENTIONS: Abnormal lymph nodes were sampled by FNA for
      cytology. RESULTS: There was agreement on the T stage by linear and radial
      techniques in 38 of 43 subjects (88%). Twenty-seven of 43 patients (63%) had
      abnormal lymph nodes by linear or transverse-array imaging. L-EUS demonstrated 66
      abnormal lymph nodes in 27 subjects (average of 2.4 nodes/subject). TA-EUS
      demonstrated 90 abnormal lymph nodes in 27 subjects (average of 3.3
      nodes/subject, P = .009, compared with L-EUS). In 16 of the 27 subjects, an FNA
      was performed, which was positive in 13 cases (81%) and negative in 3 cases (10%)
      for malignancy. CONCLUSIONS: TA-EUS and L-EUS provide similar results of T
      staging of UGI malignancies. However, the number of abnormal lymph nodes detected
      by TA-EUS was more than by L-EUS. These findings suggest that radial or
      transverse-array EUS imaging should be the primary method for staging of UGI
      malignancies.

PMID- 16996339
TI  - Choosing from the expanding EUS armamentarium menu: high-frequency probes, radial
      or linear endosonography for staging of upper GI malignancy?

PMID- 16996340
TI  - Advantage of EUS Trucut biopsy combined with fine-needle aspiration without
      immediate on-site cytopathologic examination.
AB  - BACKGROUND: Endoscopic ultrasonographically guided fine-needle aspiration (EUS
      FNA) is a safe and accurate method for obtaining diagnostic material from lesions
      within and immediately adjacent to the upper GI tract. OBJECTIVE: To determine
      whether EUS Trucut biopsy (EUS-TCB) (Quickcore, Wilson-Cook, Winstom Salem, NC)
      can increase the accuracy of EUS-guided tissue sampling when combined with FNA
      when no cytopathologist is present. DESIGN: Retrospective case review. SETTING:
      University-based referral practice. PATIENTS: All patients who had lesions that
      were accessible through the esophagus or stomach and that were greater than 20 mm
      and amenable to Trucut biopsy were included. INTERVENTIONS: A total of 41
      patients underwent both EUS-FNA and TCB with a separate pathologist evaluating
      each specimen. MAIN OUTCOME MEASUREMENTS: The diagnostic performance of FNA, TCB,
      and its combination were compared. RESULTS: The overall accuracy in our series
      was as follows: FNA, 76%; TCB, 76% (P not significant); and combination of FNA
      and TCB, 95% (P = .007). In the 26 patients with malignant diagnoses, the
      accuracy of combination was 100% versus 77% for FNA (P = .03). The median number
      of passes with the FNA and TCB was 4.4 (range 2-8) and 2.8 (range 2-5),
      respectively. One patient in the series had fever and chest pain after EUS
      biopsy. LIMITATIONS: Retrospective study. CONCLUSION: In our series EUS-TCB
      accuracy was equal to FNA when no on-site cytopathologist is present. TCB was
      helpful in the diagnosis of pancreatic masses, gastric submucosal lesions,
      lymphoma, and necrotic tumors. A 100% accuracy of FNA + TCB was seen in patients
      with malignant diseases and in patients who had failed or been refused biopsy by
      other modalities in the past. More data are needed before the exact role of TCB
      in the absence of on-site cytopathology can be accurately defined.

PMID- 16996341
TI  - Preoperative diagnosis and management of thick-walled gallbladder based on bile
      cytology obtained by endoscopic transpapillary gallbladder drainage tube.
AB  - BACKGROUND: It is often difficult to distinguish gallbladder cancers (GBC) from
      benign gallbladder diseases, which show thickened walls. OBJECTIVES: To evaluate
      the efficacy of bile cytology using endoscopic transpapillary gallbladder
      drainage (ETGD) and CT. DESIGN: Retrospective study. SETTING: Division of
      Gastroenterology, Tokyo Medical University, Tokyo, Japan. PATIENTS AND
      INTERVENTIONS: Eighty-five patients with gallbladder diseases, consisting of 27
      GBC and 58 benign gallbladder diseases, were reviewed. A pigtail-type
      nasobilliary drainage tube was left indwelling in the gallbladder, and through
      this drainage tube washing cytology was performed with an ETGD tube. MAIN OUTCOME
      MEASUREMENTS: Diagnostic accuracy of CT and cytology. Complications and outcome
      were also evaluated. RESULTS: CT and cytology with the ETGD tube had 81% and 81%
      sensitivity, 91% and 83% specificity, and 88% and 82% accuracy, respectively (P >
      .05). Looking only at the 71 successful ETGD cases, CT and ETGD cytology had 82%
      and 100% sensitivity, 92% and 98% specificity, and 89% and 99% accuracy,
      respectively (P = .036 and .025, respectively). Four patients with GBC in whom CT
      showed benign findings underwent open cholecystectomy because ETGD cytology
      revealed malignant findings. In contrast, 4 patients with benign diseases in whom
      CT suggested malignant finding underwent LC because the findings of ETGD cytology
      suggested benign disease. CONCLUSIONS: Cytology using an ETGD tube is very useful
      in the diagnosis and management of gallbladder diseases.

PMID- 16996342
TI  - Transpapillary cytology analysis helps to distinguish benign from malignant
      gallbladder disease. Should we do it?

PMID- 16996343
TI  - Risk factors for cholecystitis after metal stent placement in malignant biliary
      obstruction.
AB  - BACKGROUND: Cholecystitis related to metal stent placement is a morbid event.
      OBJECTIVE: This study evaluated the risk factors of cholecystitis after metal
      stenting for malignant biliary obstruction. PATIENTS: Between December 1997 and
      April 2003, 155 patients who were treated with a metal stent for malignant
      biliary obstruction were retrospectively enrolled. MAIN OUTCOME MEASUREMENTS: The
      incidence and characteristics of patients with cholecystitis were evaluated and
      compared with those of patients without cholecystitis. Patient characteristics
      and tumor or procedure-related data were recorded for the following variables:
      sex, age, tumor and stent length, stent type (covered vs uncovered), cholangitis
      before ERCP, degree of gallbladder filling with contrast medium during ERCP,
      primary disease type (Klatskin vs others), presence of gallbladder stones, and
      the relationship of the cystic duct orifice to the location of the tumor (across
      vs others). RESULTS: There were 15 (9.7%) patients diagnosed with cholecystitis
      after metal stent insertion. The onset of cholecystitis was on average 4.6 days
      (range 1 to 26) after the procedure. We found that an obstruction across the
      cystic duct orifice by tumor (P < .01, odds ratio 12.7) and the presence of
      gallbladder stone (P = .01, odds ratio 6.6) were positively related to the
      cholecystitis after metal stent insertion. LIMITATIONS: The limitations of the
      study were the use of multiple types of stents and the retrospective design.
      CONCLUSIONS: This study demonstrated that an obstruction across the cystic duct
      by tumor and the presence of gallbladder stone were risk factors for the
      development of cholecystitis after metal stent placement.

PMID- 16996344
TI  - Video capsule endoscopy compared with standard endoscopy for the evaluation of
      small-bowel polyps in persons with familial adenomatous polyposis (with video).
AB  - BACKGROUND: Video capsule endoscopy (VCE) may be useful for surveillance of small
      bowel polyps in patients with familial adenomatous polyposis (FAP). OBJECTIVE: To
      compare VCE to standard endoscopy for diagnosing small-bowel polyps in a defined
      segment of small bowel (proximal to a tattoo) and the entire examined small
      bowel. DESIGN: Prospective. SETTING: Single tertiary referral center. PATIENTS:
      Participants with FAP (n = 32). The majority were selected for their high number
      of proximal small-bowel polyps and prior endoscopic tattoo placement in the
      proximal small bowel. INTERVENTIONS: VCE (interpreted by 2 readers), push
      enteroscopy (PE), and lower endoscopy (LE) to count and measure small-bowel
      polyps. RESULTS: In the defined segment, VCE detected a median of 10.0
      (interquartile range [IQR], 5.0-19.0) and 9.0 (IQR, 6.0-16.0) polyps for each
      reader compared with a median of 41.0 (IQR, 19.0-64.0) polyps on PE (P = .002).
      Agreement between the 2 methods was fair (kappa = 0.34, 0.36). Agreement between
      VCE and PE was poor to fair (kappa = 0.10, 0.22) for estimating the size of the
      largest polyp and poor (kappa = -0.20, -0.27) for detecting large polyps (> or =1
      cm). In the entire examined small bowel, VCE diagnosed a median of 38.0 (IQR,
      10.5-71.5) and 54.0 (IQR, 13.0-100.0) polyps for each reader compared with a
      median of 123.0 (IQR, 38.5-183.0) for combination endoscopy (PE and LE) (P <
      .001). Agreement between the 2 methods was fair to moderate (kappa = 0.21, 0.56).
      LIMITATIONS: Participants selected for high polyp burden, and results may not be
      applicable to all patients with FAP. CONCLUSIONS: VCE underestimates the number
      of small-bowel polyps in persons with FAP and does not reliably detect large
      polyps.

PMID- 16996345
TI  - Limited ability of capsule endoscopy to detect normally positioned duodenal
      papilla.
AB  - BACKGROUND: The current power of capsule endoscopy (CE) to diagnose patients with
      obscure GI bleeding is 42% to 74.4%. OBJECTIVE: The aim of this study was to
      evaluate the diagnostic power of CE through its ability to detect duodenal
      papilla. DESIGN AND PATIENTS: A total of 112 consecutive CEs were retrospectively
      reviewed. All patients had undergone esophagogastroduodenoscopy and had their
      normal duodenal papilla confirmed. SETTING AND INTERVENTIONS: The CE findings
      were reviewed separately at a rate of 15 images/second by 2 experienced and
      competent capsule readers. MAIN OUTCOME MEASUREMENTS: The CE detection rate of
      duodenal papilla was calculated. In addition, the number of frames showing
      duodenal papilla was counted. RESULTS: Among the total CEs, 2 cases were excluded
      because the capsule could not traverse the second portion of duodenum. The most
      common indication was obscure GI bleeding. CE only detected duodenal papilla in
      48 cases (43.6%). The mean number of frames of the visualizing duodenal papilla
      was 3.5 +/- 2.5 (range 1-13). LIMITATIONS: Choosing duodenal papilla as the
      reference may not be optimal because its position is difficult to identify.
      CONCLUSIONS: Our study conveys an important message on the present power of CE;
      we should carefully review CE findings at a slower review rate to raise the
      detection ability of the current-powered CE, when it is passing through several
      "difficult to identify" locations such as second portion of the duodenum. In
      addition, to raise the power of CE, technologic improvements of CE, such as an
      extracorporeal-controllable device or a multiside viewing capsule, are needed.

PMID- 16996346
TI  - Is half-knowledge worse than ignorance?

PMID- 16996347
TI  - A randomized prospective trial comparing different regimens of oral sodium
      phosphate and polyethylene glycol-based lavage solution in the preparation of
      patients for colonoscopy.
AB  - BACKGROUND: Regulatory agencies have warned clinicians regarding the risk of
      electrolyte abnormalities if more than two 45-mL bottles of oral sodium phosphate
      (NaP) solution are administered within a 24-hour period. OBJECTIVE: To compare
      the efficacy, safety, and tolerability of different regimens of oral NaP and
      polyethylene glycol (PEG). DESIGN: Randomized controlled trial. SETTING: Teaching
      hospital outpatient endoscopy clinic. PATIENTS: Two hundred outpatients without
      comorbidities who underwent routine colonoscopy. INTERVENTIONS: Two bottles of
      NaP, 6, 12, or 24 hours apart; or 4 L PEG. MAIN OUTCOME MEASUREMENTS: Bowel
      preparation quality, patient tolerability, and electrolyte changes. RESULTS: The
      12- and 24-hour NaP achieved better cleansing than the 6-hour NaP or PEG. Only
      8.5% and 8.3% of patients in the 24- and 12-hour NaP had poor preparations,
      respectively, compared with 15.6% and 23.4% in the 6-hour NaP and PEG,
      respectively. The poorer preparation scores with PEG were partly because of a
      greater amount of colonic fluid. There were no relevant electrolyte changes with
      PEG, whereas hypokalemia, hypocalcemia, or hyperphosphatemia developed in 5% to
      57% of patients on NaP. All regimens were poorly tolerated by patients.
      LIMITATIONS: The study was likely underpowered to detect small group differences
      in electrolytes. CONCLUSIONS: A 24- or 12-hour NaP bowel preparation strategy was
      more effective than NaP 6 hours apart or PEG. PEG use is associated with more
      residual colonic fluid but represents an alternative to NaP in some clinical
      situations.

PMID- 16996348
TI  - Take two phosphasodas and scope them in the morning...

PMID- 16996349
TI  - Colonoscopy completion and complication rates in a community gastroenterology
      practice.
AB  - BACKGROUND: In the United States, colonoscopy completion and complication rates
      are rarely reported outside academic institutions. Increased transparency of
      quality measures and outcomes is being driven by professional societies,
      government agencies, and private enterprise. OBJECTIVE: To collect and report the
      completion and complication rates of colonoscopy in a community gastroenterology
      practice. DESIGN: Single-center study, prospective for completion, retrospective
      for complications. SETTING: Community gastroenterology group practice, conducted
      from August 2002 through December 2004. PATIENTS: A total of 12,407 consecutive
      patients referred for colonoscopy; mean age, 59.7 years; 5925 men. INTERVENTIONS:
      Polypectomy and cautery were completed as indicated. MAIN OUTCOME MEASURES:
      Completion of colonoscopy to cecum or ileocolonic anastomosis. Complications of
      hemorrhage and perforation. RESULTS: A colonoscopy was completed in 98.4% of
      patients. Polypectomy was accomplished in 5074 (40.9%). Polyps occurred more
      often in men (46.4% vs 35.8%, P < .001). Causes for failure included difficult
      anatomy (55.9%), inadequate preparation (20.8%), obstructing malignancy (8.6%),
      discomfort (8.1%), and severe inflammation (6.1%). Failure from difficult anatomy
      was more likely in women (1.19% vs 0.56%, P < .001). Hemorrhage requiring
      hospitalization occurred after 25 cases (0.20%). Twenty-three episodes of
      bleeding occurred after polypectomy (0.46%) and 2 after treatment of
      arteriovenous malformations. Two perforations occurred (0.016%). One patient
      developed a posterior circulation stroke. No deaths occurred. LIMITATIONS:
      Completion not independently verifiable. Complications were collected
      retrospectively. CONCLUSIONS: Colonoscopy completion and complication rates in
      this community gastroenterology practice compared favorably with U.S. academic
      centers. Endoscopic quality in community practices can meet published outcomes.

PMID- 16996350
TI  - Home repair and colonoscopy: quality counts.

PMID- 16996351
TI  - Quality of patient referral information for open-access endoscopic procedures.
AB  - BACKGROUND: Increased demand for endoscopic procedures has led to the provision
      of these services without prior consultation (open access). The need for accurate
      medical referral information for these patients is vital for patient safety.
      OBJECTIVE: To assess the accuracy of endoscopic referral information. DESIGN:
      Over a 4-month study period, patient referral forms were evaluated to determine
      the accuracy of medical information on patient referral forms by using direct
      interview with the patient and/or the caregiver. Inconsistencies were validated
      against medical records. SETTING: Large academic medical clinic. PATIENTS: A
      total of 868 open-access patient referrals for upper endoscopy and colonoscopy
      services. MAIN OUTCOME MEASUREMENTS: Referral information about medical
      diagnoses, medications, allergies, need for antibiotic administration, and
      current coagulopathies. RESULTS: Inaccurate medical referral information was
      provided to the endoscopist in 8.8% of referrals (n = 76). Among referrals
      containing errors, there were a total of 95 significant medical information
      errors, which, if left undetected by preprocedure review, could have resulted in
      serious adverse consequences for patients undergoing endoscopy. LIMITATIONS:
      Study limited to an academic clinical setting. CONCLUSIONS: Patient referrals for
      endoscopic services in an open-access referral system contain unacceptably high
      numbers of errors, which place patients at risk for adverse outcomes from
      endoscopic procedures.

PMID- 16996352
TI  - The Neo-Papilla: a new modification of porcine ex vivo simulators for ERCP
      training (with videos).
AB  - BACKGROUND: Computer simulators, live pigs, and ex vivo porcine simulators are
      used for training in ERCP. The location of the porcine biliary orifice in the
      proximal duodenum is dissimilar to human anatomy, making the endoscopy experience
      less realistic. In addition, in native porcine anatomy, the pancreatic duct
      enters the duodenum distal to the biliary orifice, limiting the teaching of
      pancreatic techniques and selective duct cannulation. OBJECTIVE: To overcome
      these limitations, we aimed to construct a Neo-Papilla that could be incorporated
      into an ex vivo model. DESIGN: We attached chicken heart tissue to the porcine
      duodenum, with integrated porcine arteries that resembled an artificial common
      bile duct and a pancreatic duct. SETTING: The simulator was presented and
      evaluated at 2 major GI endoscopy conferences. MAIN OUTCOME MEASUREMENTS: The
      feasibility and the realism of this prototype was tested by 9 recognized ERCP
      experts who rated this model in comparison to other teaching models for ERCP by
      recollection of prior experience. RESULTS: The Neo-Papilla was more prominent and
      more distally located than the native porcine papilla. The experts rated this
      modification superior to existing models in its usefulness as an educational
      tool. LIMITATIONS: Pilot study. CONCLUSIONS: We demonstrated the technical
      feasibility of a real-tissue Neo-Papilla modification of porcine ex vivo
      simulators, more closely approximating the natural anatomy. This new model should
      facilitate ERCP training. Formal validation studies are warranted.

PMID- 16996353
TI  - Tissue anchors for transmural gut-wall apposition.
AB  - BACKGROUND: With the development of NOTES (natural orifice transluminal
      endoscopic surgery) and efforts to advance gastric reduction surgery,
      alternatives for robust tissue apposition apart from suturing and current mucosal
      clipping devices may be valuable. OBJECTIVES: We attempted to identify functional
      tissue anchors that could be deployed endoscopically, with the potential to
      provide transmural tissue apposition. DESIGN: Short-term animal-survival study.
      PATIENTS: Domestic pigs, under general anesthesia, underwent open laparotomy,
      gastrotomy, and manual placement of prototype tissue anchors. INTERVENTIONS: Four
      tissue-anchor designs were evaluated (T bar, T bar with mesh bolster, star,
      basket). Full-thickness gastric plications were manually created in the body and
      the antrum via laparotomy and were secured with sets of paired anchors, also
      placed manually via a gastrotomy. In 1 test animal, a pilot gastric reduction was
      created by forming 2 rows of 4 anchor sets on the anterior and posterior walls to
      create a tubelike gastric lumen. MAIN OUTCOME MEASUREMENTS: Follow-up endoscopy
      was performed at 2, 4, and 9 weeks to visually assess the intraluminal appearance
      of the plications, followed by necropsy and histologic study. RESULTS: There was
      an overall attrition of the number of anchor sets. At 2 weeks, the T-bar anchors
      were first to disappear, and the mesh and the star designs began to pull through
      the gastric folds. At 4 weeks, there was flattening of the plications that
      involved 6 pairs of mesh anchors. By 9 weeks, 3 pairs of mesh anchors were lost
      and 3 pairs were associated with flattened folds. At the time of euthanasia, at 4
      or 9 weeks, the number of retained anchors associated with intact plications for
      each group were as follows: T bar, 6 of 9 pairs (67%); mesh, 12 of 18 pairs
      (67%); basket, 14 of 18 pairs (78%); and star, 2 of 9 pairs (22%). There were no
      gastric adhesions and no evidence for any inflammatory changes surrounding the
      stomachs. The tallest plications involved the basket anchors. The basket-anchored
      plications contained apposed muscularis propria, with serosal fusion evident. The
      folds from the other anchor types were formed of mucosa and submucosa with or
      without superficial muscularis propria. CONCLUSIONS: The results of this
      experience are encouraging. The basket tissue anchors appear most promising.
      These findings suggest that further development of tissue anchors deployed via
      flexible catheter-based devices may have clinical value for transmural tissue
      apposition.

PMID- 16996354
TI  - Comparison of Pelican single-use multibite biopsy forceps and traditional double
      bite forceps: evaluation in a porcine model.
AB  - BACKGROUND: The multibite biopsy forceps is intended for consecutive acquisition
      of numerous tissue specimens with a single pass. The Pelican multibite forceps is
      equipped with a sleeve for tissue retention that allows up to 6 specimens to be
      obtained with each pass of the device through the accessory channel. Reducing the
      need for device exchange could decrease the total procedure time for colon cancer
      surveillance in patients with longstanding inflammatory bowel disease (IBD).
      OBJECTIVE: The aim of this study was to evaluate a new multibite biopsy forceps
      in comparison with a standard double-bite forceps. DESIGN: Prospective randomized
      animal model trial. SETTING: Multicenter university and community hospitals.
      INTERVENTIONS: By using a live porcine model, multiple colonoscopic biopsy
      specimens were obtained with both the Pelican multibite forceps and the Radial
      Jaw 3 (RJ3) double-bite forceps to mimic colorectal cancer surveillance in
      patients with IBD. Six biopsy specimens were obtained with each of 6 passes when
      using the Pelican forceps, and 2 biopsy specimens were obtained with each of 18
      passes when using the RJ3 forceps. MAIN OUTCOME MEASUREMENTS: All trials were
      timed. Two independent pathologists blinded to the forceps used evaluated the
      specimens. RESULTS: Tissue acquisition when using the Pelican multibite forceps
      was significantly faster than with a standard double-bite forceps. The devices
      compared equivalently for specimen retention and quality. LIMITATIONS: The
      operator could not be blinded to the devices used. This study uses an animal
      model to extrapolate how the devices might perform in human use. CONCLUSIONS:
      These findings support the evaluation of the Pelican forceps for colon cancer
      surveillance in patients with longstanding IBD.

PMID- 16996355
TI  - Simultaneous fluorescence imaging of protease expression and vascularity during
      murine colonoscopy for colonic lesion characterization.
AB  - BACKGROUND: Molecularly targeted fluorescent probes are currently being developed
      to improve the endoscopic detection of intestinal pathologic conditions.
      OBJECTIVE: We report on the development and testing of a novel multichannel
      microendoscope capable of quantitatively reporting such probes simultaneously at
      different wavelengths in real time. We assessed the feasibility of detecting and
      quantifying beacons that can be activated by protease and correlating imaging
      with disease state. DESIGN: The microendoscope consisted of a 20-gauge fiberoptic
      catheter and dichroic beam splitters that simultaneously display visible light,
      700 nm and 800 nm near infrared (NIR) fluorescent light. NIR interchannel
      separation was tested on in vitro phantoms. Two mouse models were used (Apcmin(+/
      ) mice for colonic adenomas and CT26 murine colon cancer). A perfusion probe and
      one activated by protease at a separate wavelength were injected before
      endoscopic evaluation. RESULTS: The microendoscope fluorochrome detection limit
      was approximately 10 fmol; ratio imaging in the NIR was accurate (+/-8% of true
      probe concentration between 0.3 to 100 microg/ml of a protease sensor). Both
      colonic adenomas and adenocarcinomas were clearly visible in the NIR channel on
      protease probe administration in live mice. Ratio imaging of protease
      activity/perfusion increased from healthy colon to adenomas to adenocarcinomas.
      LIMITATIONS: Evaluation across additional spontaneous tumor models may provide
      more data on the translation of these findings. CONCLUSIONS: Our data show the
      feasibility of multichannel microendoscopic imaging of molecular targets in vivo
      and that ratio imaging may provide a novel means for characterizing colonic
      lesions. When scaled up clinically, this could aid in increasing lesion detection
      and quantitative assessment of distinct molecular markers.

PMID- 16996356
TI  - Getting involved in gastroenterology beyond the borders of your fellowship
      program.

PMID- 16996357
TI  - High-magnification colonoscopy (with videos).

PMID- 16996358
TI  - Incidence of advanced adenomas at surveillance colonoscopy in patients with a
      personal history of colon adenomas: a meta-analysis and systematic review.
AB  - BACKGROUND: Current guidelines stratify patients with a personal history of
      adenomas as low risk (ie, 1-2 small [<10 mm] adenomas at index colonoscopy) or
      high risk (> or =3 small adenomas or advanced adenoma at index colonoscopy) for
      recurrent advanced adenomas. Guidelines recommend longer intervals between
      surveillance colonoscopies for low-risk patients, but physicians frequently
      perform surveillance colonoscopy at shorter intervals for these patients.
      OBJECTIVE: Our purpose was to perform a meta-analysis about the incidence of
      advanced adenomas at 3-year surveillance colonoscopy among high- and low-risk
      patients. METHODS: Computer searches of MEDLINE, PREMEDLINE, and EMBASE were
      performed to identify appropriate studies. Study selection criteria were (1)
      study design--prospective or registry-based study, (2) study population--patients
      with a personal history of adenomas, and (3) intervention--completion of
      surveillance colonoscopy at an interval of > or =2 years. Data were extracted on
      (1) incidence of advanced adenomas at surveillance colonoscopy, (2) interval
      between colonoscopies, and (3) risk factors associated with recurrent adenomas.
      After the validity of study design was assessed and independent, duplicate data
      extraction was performed from selected trials, summary relative risks (RR) for
      the incidence of advanced adenomas at 3-year colonoscopy were calculated.
      RESULTS: Fifteen studies met study selection criteria, but only 5 studies
      stratified surveillance colonoscopy results according to findings at the index
      colonoscopy. Patients with > or =3 adenomas at index colonoscopy were more likely
      to have recurrent advanced adenomas than were patients with 1 to 2 adenomas: RR
      2.52, 95% CI 1.07-5.97. Patients with adenomas with high-grade dysplasia at index
      colonoscopy were also at increased risk for recurrent advanced adenomas: RR 1.84,
      95% CI 1.06-3.19. In the individual studies, increasing size of adenomas and
      increasing number of adenomas at index colonoscopy were the most commonly
      reported risk factors associated with recurrent advanced adenomas. No studies
      stratified surveillance colonoscopy results according to the definitions of low
      risk and high risk used in current guidelines. CONCLUSION: Few published studies
      stratify the incidence of advanced adenomas at surveillance colonoscopy according
      to index colonoscopy findings. In the future, large prospective studies or
      studies using pooled data from existing randomized controlled trial databases or
      polyp registries should be used to better define which patients are at low risk
      for advanced adenoma recurrence.

PMID- 16996359
TI  - Endoscopic holder-assisted percutaneous endoscopic gastrostomy placement: results
      of a prospective, randomized comparison study.
AB  - BACKGROUND: We developed a new method of endoscope holder-assisted percutaneous
      endoscopic gastrostomy (PEG) placement requiring only a single physician.
      OBJECTIVE: This study compared the feasibility and safety of the new method with
      the conventional pull method of PEG performed by 2 physicians. DESIGN:
      Prospective, randomized comparison study. SETTING: Rural municipal hospital.
      PATIENTS: Eighty consecutive patients with dysphagia. INTERVENTIONS: Patients
      were randomized to receive PEG placement by a single physician using the
      endoscope holder (40 patients) or by 2 physicians using the conventional pull
      method (40 patients). MAIN OUTCOME MEASUREMENTS: The success rate, duration, and
      complications of both methods were scored. RESULTS: The success rate of PEG by
      either method was similar (98%) using the endoscope holder compared with 100%
      with the conventional method. The duration of both endoscopic procedures was also
      similar (12.9 +/- 2 and 11.5 +/- 2 minutes) (P = .43). No major complication
      occurred with either procedure. There was 1 death within 30 days (of aspiration
      pneumonia) 3 days after conventional PEG placement. LIMITATIONS: The number of
      patients evaluated is small. CONCLUSIONS: Endoscope holder-assisted PEG placement
      allows a single physician to perform all the important aspects of pull PEG
      placement under direct vision without assistance from another specially trained
      individual. The method appears to be as feasible and safe as the conventional
      pull method.

PMID- 16996360
TI  - Endoscopic therapy of a splenic abscess: definitive treatment via EUS-guided
      transgastric drainage.
AB  - BACKGROUND: Splenic complications of pancreatitis are exceedingly rare, occurring
      in only 2.2% of cases. Patients typically present in a dramatic fashion and often
      need an urgent procedure to prevent overwhelming infection or hemorrhage.
      Historically, the procedures involve surgery (distal pancreatectomy and
      splenectomy) or percutaneous drainage. SETTING: Walter Reed Army Medical Center.
      PATIENT: A patient with acute or chronic pancreatitis presented with pleuritic
      chest pain and fever up to 105 degrees F (40.6 degrees C). A CT of the abdomen
      and the pelvis demonstrated a splenic abscess. INTERVENTION: Because of the
      technical inability to perform transpapillary drainage, EUS-guided transgastric
      drainage resolved the splenic abscess. CONCLUSIONS: This is the first reported
      case of a splenic abscess treated definitively with endoscopic therapy. In the
      face of a worsening clinical picture and reported morbidities up to 79% with
      surgical and percutaneous drainage procedures, endoscopic therapies should be
      considered in the management of splenic complications of pancreatitis.

PMID- 16996361
TI  - Three-dimensional US volume analysis of gastric pseudotumors in a porcine model.
AB  - BACKGROUND: Tumor burden is difficult to estimate by endoscopy and conventional
      EUS. OBJECTIVE: The purpose of this study was to determine the accuracy and the
      reliability of a new 3-dimensional (3D) EUS system in a pseudotumor model
      (Olympus EUS EXERA EU-M60). DESIGN: A pseudotumor model was developed in a
      porcine stomach. Pseudotumors were created by injecting various volumes of US gel
      (0.3, 0.5, 0.7, and 1 mL) into porcine stomach specimens, and then the volume was
      measured in vitro. Two investigators made volume measurements by outlining the
      cross-sectional area of the pseudotumor at different radial planes. The
      instrument then automatically calculated the volume based on the outlined cross
      sectional areas. The measured volume was compared with the actual volume of the
      pseudotumor by using a Bland-Altman analysis. Every second, third, fourth, fifth,
      sixth, and tenth image was measured to calculate the tumor volume and to
      determine the optimum number of images required for accurate volume
      determination. Inter- and intraobserver variability, percentage error, Bland
      Altman analysis, analysis of variance (ANOVA), and kappa statistic were
      performed. SETTING: This study was performed in an in vitro animal model.
      PATIENTS: There were no patients involved in this study. MAIN OUTCOME
      MEASUREMENTS: Accuracy and reliability of pseudotumor volume measurement.
      RESULTS: When averaging across all measurements, the overall average mean error
      was 3.25%. The overall inter-rater reliability as measured by intraclass
      correlation coefficient was 0.78. The overall intra-rater reliability as measured
      by intraclass correlation coefficient was 0.99. Bland-Altman analysis and ANOVA
      showed similar low variability for measured volumes based on image frequencies
      for volume calculations between every other and every sixth image but greater
      variability for measured volumes based on every tenth image. Larger pseudotumors
      were measured with a slight decrease in mean percentage error. The kappa
      statistic for interobserver variability was .61, which demonstrated substantial
      agreement among observers. LIMITATIONS: The major limitation of this technology
      is the penetration of the US beam to evaluate large tumors, because the US
      transducer is high frequency (20 MHz) and, therefore, has a limited penetration.
      CONCLUSIONS: In conclusion, the new Olympus EUS EXERA EU-M60 3D US probe allowed
      for accurate volume measurements of small pseudotumors in porcine stomach model
      in vitro. There was substantial evaluator agreement, with a low interobserver
      variability. Larger pseudotumors were measured with a slightly lower percentage
      error than smaller pseudotumors. Volumes measured with a greater number of radial
      images were measured slightly more accurately. We plan to test this device in
      patients with GI tumors in the near future.

PMID- 16996362
TI  - Endoluminal closure of large perforations of colon with clips in a porcine model
      (with video).
AB  - BACKGROUND: Endoluminal clip closure of small perforations of the colon is
      possible. It is unclear whether large perforations of the colon can be closed
      with clips deployed through a colonoscope. OBJECTIVES: To evaluate the technical
      feasibility and outcome of endoluminal closure of large perforations of the colon
      with clips. DESIGN: Pilot study. SUBJECTS: Eight pigs. INTERVENTIONS: Endoluminal
      clip closure of large perforations of the colon. MAIN OUTCOME MEASUREMENTS:
      Technical feasibility of endoluminal closure was evaluated in 8 animals. A dye
      leak test was performed to evaluate quality of endoluminal sealing immediately
      after closure and 2 weeks after closure. The animals in the survival group were
      monitored daily for 2 weeks for sepsis and peritonitis. Necropsy was done on day
      14 to check for fecal peritonitis, wound dehiscence, and histological healing of
      perforation. RESULTS: Endoscopic closure of colon perforation was successful in 6
      of 8 animals; in 2 animals closure was unsuccessful due to prolapse of adjacent
      viscera into the colon (n = 1) and severe bleeding that obscured the view (n =
      1). There was a leak-proof sealing of the perforation site in 2 animals tested
      immediately and in all the animals tested (n = 3) 2 weeks after closure. All 4
      animals in the survival group recovered well, without any sepsis or peritonitis.
      Necropsy did not reveal fecal peritonitis or pericolonic abscess formation. The
      perforation site demonstrated a thin scar and there was histological healing.
      CONCLUSIONS: Endoluminal application of clips is successful in the closure of a
      large perforation of the colon in a porcine model.

PMID- 16996363
TI  - Paraprosthetic fistula in a patient presenting with fever and lumbar pain.

PMID- 16996364
TI  - Duodenal tuberculosis.

PMID- 16996365
TI  - Use of capsule endoscopy in children with primary intestinal lymphangiectasia.

PMID- 16996366
TI  - Intestinal parasites seen on capsule endoscopy.

PMID- 16996367
TI  - EUS-guided FNA diagnosis of recurrent follicular lymphoma in the transverse
      colon.

PMID- 16996368
TI  - Endoscopic treatment of an iatrogenic perforation of the colon by using endoloop.

PMID- 16996369
TI  - Synchronous abdominal soft-tissue sarcomas: an unusual case of upper-GI bleeding
      diagnosed by EUS-guided FNA.

PMID- 16996370
TI  - Detection of recurrent extrahepatic hepatobiliary cystadenoma by EUS (with
      video).

PMID- 16996371
TI  - EUS-guided FNA diagnosis of pancreatic tuberculosis.

PMID- 16996372
TI  - EUS-guided choledochoduodenostomy for palliative biliary drainage in case of
      papillary obstruction: report of 2 cases.

PMID- 16996373
TI  - The "Quill" technique--another method for managing buried bumper syndrome.

PMID- 16996374
TI  - Large B-cell lymphoma of the duodenal papilla presenting as pneumobilia.

PMID- 16996375
TI  - Parallel rendezvous in ERCP.

PMID- 16996377
TI  - Gastrointestinal stromal tumor of the prostate: a case report and literature
      review.
AB  - We report a case of gastrointestinal stromal tumor (GIST) of the prostate in a 75
      year-old man with dysuria and urinary retention. Digital rectal examination
      revealed a markedly enlarged prostate. The serum level of prostate-specific
      antigen was 0.2 ng/dL. Imaging studies showed an expanded prostate, measuring 6.7
      x 5.6 x 5.5 cm, with heterogeneity in contrast enhancement. No metastatic disease
      was found. The pathologic diagnosis of prostatic GIST was made based on
      characteristic morphological features, immunoprofiles, and molecular analysis.
      The possibility of secondary involvement by a rectal GIST was excluded by
      radiological and intraoperative findings. To our knowledge, this is the second
      case of a primary GIST of the prostate reported in the literature.

PMID- 16996378
TI  - Is myocardial damage truly absent in inclusion body myositis with elevated
      troponin T level?

PMID- 16996380
TI  - Association between thymoma and autoimmune enteropathy in adults.

PMID- 16996383
TI  - A review and an update on the screening of epithelial ovarian cancer.

PMID- 16996384
TI  - The business of addiction treatment: A research agenda.
AB  - The social and economic costs of addiction are substantial and of great concern
      to society. Research in the past decade has led to promising therapies that
      appear to be highly effective but not widely diffused. This leads one to wonder
      if there is something about the structure, dynamics, or structure and dynamics of
      the addiction treatment industry that is getting in the way. However, there has
      been very little research in the areas of organization, finance, or management
      practices within the substance abuse treatment field-the kinds of issues that
      reduce the potential impact of addiction treatment industrywide. With this as
      background, this article introduces the Center for Organization and Management in
      Addiction Treatment (COMAT) and a special section on research in the "business of
      addiction treatment." Many other industries have experienced significant problems
      that are similar, in many respects, to those seen in substance abuse treatment,
      but research in leadership, innovation, investment, organization, and
      consolidation strategies has helped to overcome those problems. COMAT is
      dedicated to implementing and testing evidence-based methods from other
      industries to improve the outcomes performance and, ultimately, the clinical
      effectiveness of service providers in the addiction treatment field.

PMID- 16996385
TI  - The role of organization and management in substance abuse treatment: Review and
      roadmap.
AB  - To develop an understanding as to why there exists a seemingly wide gap between
      research and practice in the field of substance abuse treatment and, more
      important, to understand how this gap can be closed, researchers have focused
      their attention on the role of organizational and management factors in the
      delivery of treatment services. This article's overarching goal is to stimulate
      research and interventions that focus on these factors so as to improve the
      standards and outcomes of care in substance abuse treatment. Part 1 introduces
      the key assumptions and perspectives that guide organization and management
      research. Part 2 selectively reviews empirical studies that examine relationships
      between treatment programs' use of research-based treatment practices and
      organization and management factors. The article concludes with a discussion of
      the next important steps for research and policy.

PMID- 16996386
TI  - Patterns of organization and management in private and public substance abuse
      treatment programs.
AB  - As an organizational field, substance abuse treatment clearly includes a
      remarkable range of organizations. Yet only in the past two decades has there
      been research interest in the organizational context in which treatment is
      delivered. The goal of this article is to promote the concept of organizational
      field by summarizing findings from an ongoing research program and by examining
      the organizational structure, service delivery, and patterns of innovation
      adoption in two large samples of substance abuse treatment programs in the United
      States. Among highlighted findings, there are notable differences between the
      public and private sectors in structural and staffing characteristics, as well as
      in the characteristics of clients receiving substance abuse treatment. With
      regard to the use of evidence-based practices, our findings suggest that
      pharmacotherapies are more likely to be adopted in private centers, whereas
      notably effective voucher approaches are more common in public centers. Future
      research directions are discussed.

PMID- 16996387
TI  - Does America spend enough on addiction treatment? Results from public opinion
      surveys.
AB  - Addiction treatment is often misunderstood and underappreciated in the United
      States. Although a large body of literature clearly demonstrates the clinical and
      economic benefits of addiction treatment for many clients and in most settings,
      the general public has a somewhat ambivalent attitude toward treatment expansion
      and taxpayer financing. A potential reason for this disconnect between economic
      evidence and public opinion is a weak identification with the need for, or the
      success of, addiction treatment for those individuals without a substance abuse
      problem themselves or in members of their family. Alternatively, addiction
      treatment stakeholders may be delivering an ineffective or misdirected message
      about the social value of this industry. This article explores these and other
      potential explanations for the paradoxically low placement of the addiction
      treatment industry among other socially important institutions in the United
      States. Although none of the explanations advanced in this article has been
      scientifically tested or verified, it is hoped that the historical inquiry and
      information provided herein will offer practical strategies for the stability and
      growth of the addiction treatment industry.

PMID- 16996388
TI  - Industry evolution through consolidation: Implications for addiction treatment.
AB  - Drawing on experiences in other industries, this article argues that the business
      of addiction treatment is likely to be transformed by the advent of a period of
      consolidation, in which a number of small independent programs will be acquired
      by larger, better capitalized, and managerially more sophisticated enterprises.
      Consolidation will be driven by opportunities to leverage new technologies, to
      exploit new regulatory initiatives, and to introduce economies of scale and scope
      into an industry that is currently highly fragmented. The process is likely to
      result in segmentation of the market, with the coexistence of large, generalist,
      highly standardized firms and a number of small highly specialized firms. When an
      industry consolidates, the types and quality of services provided can improve
      through the adoption of best practices and through increased competition among
      larger providers. If these larger providers are publicly traded, however, efforts
      to improve will inevitably be influenced by pressures to maintain or increase
      quarter-to-quarter earnings and share prices, leaving open the long-term impact
      on service quality.

PMID- 16996389
TI  - Addiction treatment services and co-occurring disorders: Prevalence estimates,
      treatment practices, and barriers.
AB  - As the model for treating co-occurring disorders in addiction treatment settings
      becomes articulated, service systems need data on prevalence, current practice,
      and barriers to the implementation of evidence-based practices. A self-report
      survey was administered to 453 addiction treatment providers (43 agency
      directors, 110 clinical supervisors, and 300 clinicians) from a single state
      system of care. Data on prevalence estimates, treatment practices, and barriers
      to implementing services for co-occurring disorders were obtained. The three
      groups estimated that several co-occurring disorders were extremely common: mood
      disorders (40%-42%), anxiety disorders (24%-27%), posttraumatic stress disorder
      (24%-27%), severe mental illnesses (16%-21%), antisocial personality disorder
      (18%-20%), and borderline personality disorder (17%-18%). Practice patterns for
      patients with these co-occurring disorders differed widely, from referral to
      mental health programs to provision of integrated treatment. Common barriers to
      providing services to persons with co-occurring disorders were lack of
      psychiatric personnel and resources. Comprehensive surveys of an addiction
      treatment service system can rapidly and economically produce estimates of
      prevalence, current practices, and barriers to evidence-based practices. This
      objective information is critical for systems intending to enhance services to
      persons with co-occurring disorders.

PMID- 16996390
TI  - The contribution of consensus within staff and client groups as well as
      concordance between staff and clients to treatment engagement.
AB  - Two nonspecific organizational factors-consensus, defined as agreement within
      staff and client groups, and concordance, defined as agreement between staff and
      client groups-were shown to influence client engagement in treatment in a
      national sample of 80 residential substance abuse treatment programs including
      595 staff and 3,732 clients. Agreement was tested using a combined therapeutic
      community, cognitive-behavioral therapy, and 12-step treatment scale completed by
      staff and clients. Treatment engagement was measured by the combined scores on
      the three scales completed by the clients, including engagement, rapport with the
      counseling process, and confidence in treatment. Within-group consensus was
      measured by the standard deviations of the mean scores, whereas between-groups
      concordance was measured by the standard error of the difference between staff
      and client mean scores. Regression analyses showed that staff consensus was a
      significant independent predictor of client treatment engagement (p < .05),
      whereas client consensus approached significance (p < .10). Concordance was also
      a significant predictor of client engagement (p < .002) after controlling for
      staff and client consensus. The potential contribution of the findings to a
      better understanding of program quality and effectiveness of programmatic
      interventions is discussed.

PMID- 16996391
TI  - Screening for serious mental illness in populations with co-occurring substance
      use disorders: Performance of the K6 scale.
AB  - Serious mental illnesses (SMIs) such as schizophrenia, bipolar disorder, and
      major depression are prevalent among individuals with substance use disorders,
      particularly those in drug treatment programs. No screening tool has yet become
      the gold standard for identifying SMI among individuals with substance use
      disorders. One candidate instrument, the K6 screening scale, is brief, easy to
      administer and score, and has performed well, detecting SMI in studies using
      general population samples. We used data from the National Survey on Drug Use and
      Health to examine the K6's psychometric properties in a subsample of persons with
      substance use disorders and found that the K6 accurately screened for severe
      psychological distress associated with SMI among individuals with substance use
      disorders and across different psychiatric disorders.

PMID- 16996393
TI  - A systematic review of college student-athlete drinking: Prevalence rates, sport
      related factors, and interventions.
AB  - Alcohol use among college students has become a considerable public health
      problem. Among this group, intercollegiate athletes are at a particularly high
      risk for excessive alcohol consumption and resulting negative alcohol-related
      consequences. The purpose of our review was to systematically examine three main
      issues related to alcohol consumption among intercollegiate athletes: (a) the
      prevalence rates and alcohol consumption patterns of this group, especially in
      comparison with those of collegiate nonathletes; (b) the various factors that
      might motivate or encourage alcohol use among intercollegiate athletes, primarily
      sport-related individual and environmental variables; and (c) considerations for
      conducting alcohol-related interventions with intercollegiate athletes.

PMID- 16996392
TI  - A modified version of the Drug Abuse Screening Test among undergraduate students.
AB  - The present study assesses the prevalence of items from a modified version of the
      Drug Abuse Screening Test, Short Form (DAST-10) for substances other than alcohol
      among undergraduate students. More than 4,500 undergraduate students at a large
      Midwestern research university completed a web-based survey in 2005. Nearly 1
      every 10 undergraduate students experienced three or more DAST-10 items in the
      past 12 months. Although the prevalence of illicit drug use did not differ by
      gender, undergraduate men were significantly more likely than women to report
      DAST-10 items. Less than 6% of individuals who reported three or more drug DAST
      10 items had ever used treatment services for substance use. As a brief screening
      instrument, the DAST-10 offers promise for detecting possible drug abuse among
      college students. Based on the prevalence of drug use, colleges and universities
      are encouraged to provide screening opportunities to identify and to provide
      services for students at high risk for drug abuse.

PMID- 16996394
TI  - Oxcarbazepine monotherapy in children and adolescents: a single-center clinical
      experience.
AB  - This single-center analysis evaluated the efficacy of oxcarbazepine monotherapy
      in children and adolescents. A retrospective chart review identified 60 patients
      (male=33, female=27) aged 6 months to 17.8 years (mean age 8.2+/-4.7 years) with
      partial onset epilepsy receiving oxcarbazepine monotherapy. The range of
      oxcarbazepine dose was 6-71 mg/kg/day (mean 26.3+/-11.4 mg/kg/day). The duration
      of therapy ranged from 3 months to 8 years (mean duration 16.7+/-14.3 months).
      Fifty-one patients (85%) achieved>or=50% reduction in seizure frequency, and 25
      of 60 patients (42%) achieved seizure freedom. Ten patients (16.67%) reported
      adverse events including drowsiness, aggressive behavior, ataxia, dizziness,
      diplopia, and leg cramps. No hyponatremia or skin rash was observed. Twenty-four
      patients were switched from carbamazepine to oxcarbazepine monotherapy. In these
      patients carbamazepine was discontinued because of incidence of adverse events,
      poor seizure control, or both. Seventy-nine percent of patients switched from
      carbamazepine to oxcarbazepine monotherapy had >or=50% reduction in seizure
      frequency, and 37.5% became seizure-free. These findings suggest that
      oxcarbazepine monotherapy is effective and well tolerated in children and
      adolescents with partial epilepsy.

PMID- 16996395
TI  - Quality of life of children with benign rolandic epilepsy.
AB  - The first objective of this study was to determine the quality of life of
      children with benign rolandic epilepsy. Secondly, this investigation aimed to
      predict the influence of cognition on quality of life, controlling for the
      emotional impact of the epilepsy on the parent. Initial recruitment was through
      the major electroencephalography laboratories of metropolitan Sydney. The
      syndrome was defined using the International League Against Epilepsy
      classification. Patients underwent a comprehensive cognitive assessment, and
      parents completed the Child Health Questionnaire, Child Behavior Checklist, and
      Quality of Life in Childhood Epilepsy Questionnaire. Parental emotional impact
      was assessed using a subscale from the Child Health Questionnaire. The cohort
      included 30 patients (22 males, 8 females), mean age 9.67 years. There was a
      higher incidence of competence problems compared with normative data. The average
      psychosocial score was significantly lower than normative data. Controlling for
      parental emotional impact, general intellectual ability predicted quality of life
      in the areas of self-esteem and language. Clinical variables had minimal impact
      and were not included in the regression models. Parental emotional impact,
      however, was a major independent predictor of quality of life. Quality of life
      may be compromised in children with benign rolandic epilepsy and is related to
      cognitive variables and emotional impact of the epilepsy on the parent.

PMID- 16996396
TI  - Fetal deformations: a risk factor for obstetrical brachial plexus palsy?
AB  - The purpose of this report is to discuss the association of brachial plexus palsy
      and congenital deformations. We reviewed all charts of patients less than 1 year
      of age with obstetrical brachial plexus palsy evaluated by one of the authors
      (IA) between January 1998 and October 2005 at Miami Children's Hospital Brachial
      Plexus Center. Of 158 patients with obstetrical brachial plexus palsy, 7 had
      deformations (4.4%). Deformations were present in 32% of patients delivered by
      cesarean section, but in only 2% of patients delivered vaginally. The
      deformations were ipsilateral, involving the chest in two patients, distal arms
      in two patients, proximal arm in one patient, ear in one patient, and the leg in
      one patient. All patients with deformations had unilateral Erb's palsies. None
      had a history of maternal uterine malformation. Two presumptive mechanisms of
      injury, one causing the deformation (compressive forces) and one causing brachial
      plexus palsy at the time of delivery (traction forces), were present in all
      cases. The higher incidence of deformation in patients with obstetrical brachial
      plexus palsy born by cesarean sections and the presence of two presumptive
      mechanisms in all of the cases presented here raises the possibility that fetal
      deformations are a risk factor for obstetrical brachial plexus palsy.

PMID- 16996397
TI  - Mutational analyses of Taiwanese kindred with X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy is a neurodegenerative disorder with highly
      variable clinical presentation, including the childhood cerebral form, adult form
      adrenomyeloneuropathy, and Addison disease. The biochemical hallmark of the
      disorder is the accumulation of saturated very long chain fatty acids in all
      tissues and body fluids. This accumulation results from mutations in the ABCD1
      gene localized to Xq28. Using polymerase chain reaction and direct sequencing of
      deoxyribonucleic acid, we identified five novel mutations, including a
      microdeletion (1624 del ATC), a splicing site mutation (intervening sequence 1
      [IVS1] -2a>c), and three missense mutations (1172 T>C, 1520 G>A, and 1754 T>C),
      from Taiwanese kindred with X-linked adrenoleukodystrophy. A polymorphism
      involving a single nucleotide deletion in the intervening sequence 5 (IVS5 -6 del
      c) of the ABCD1 gene, previously misattributed as a mutation in the Chinese
      population, was also identified. The dinucleotide deletion (1415 del AG) mutation
      common in Japan and Western countries was not found as frequently in the Chinese
      and Taiwanese populations. Instead, a higher mutation frequency was observed in
      exon 6 of the ABCD1 gene among Japanese, Chinese, and Taiwanese kindred with X
      linked adrenoleukodystrophy, representing a potential mutational hotspot for
      future mutational screening among these Asian populations.

PMID- 16996398
TI  - A six-year follow-up MRI study of complicated early childhood convulsion.
AB  - We have previously reported a greater than 50% prevalence of structural brain
      abnormalities in children within 2 weeks of first complicated early childhood
      convulsion, including significant hippocampal asymmetry unrelated to edema. In a
      6-year follow-up study, 8 of the original 17 subjects were reimaged to determine
      any developments in hippocampal pathology. Three subjects manifested
      significantly greater asymmetry, and two exhibited a modest increase in asymmetry
      at follow-up compared with that present at initial magnetic resonance imaging.
      Two of the remaining three subjects manifested no change in the degree of
      hippocampal asymmetry that was already evident at initial scan, whereas in the
      final case, apparent resolution of previously identified (slight) hippocampal
      asymmetry had occurred. Elevated hippocampal T2 relaxation times did not
      consistently accord with smaller hippocampal volumes. These results suggest that
      complicated early childhood convulsion may be less benign than often supposed.

PMID- 16996399
TI  - Cerebral salt wasting syndrome in children with acute central nervous system
      injury.
AB  - The purpose of this investigation was to describe the causes, clinical pattern,
      and treatment of cerebral salt wasting syndrome in children with acute central
      nervous system injury. This retrospective study focused on patients<or=15 years
      old diagnosed with cerebral salt wasting syndrome, over a period of 7 years, in
      the pediatric intensive care unit of a tertiary care hospital. Selection criteria
      included evidence of hyponatremia (serum sodium<130 mEq/L), polyuria, elevated
      urine sodium (>120 mEq/L), and volume depletion. Fourteen patients were
      identified with cerebral salt wasting syndrome, 12 after a neurosurgical
      procedure (8 brain tumor, 4 hydrocephalus) and 2 after severe brain trauma. In 11
      patients the cerebral salt wasting syndrome was diagnosed during the first 48
      hours of admission. Prevalence of cerebral salt wasting syndrome in neurosurgical
      children was 11.3/1000 surgical procedures. The minimum sodium was 122+/-7 mEq/L,
      the maximum urine osmolarity 644+/-59 mOsm/kgH2O. The maximum sodium supply was 1
      mEq/kg/h (range, 0.1-2.4). The mean duration of cerebral salt wasting syndrome
      was 6+/-5 days (range 1-9). In conclusion, cerebral salt wasting syndrome can
      complicate the postoperative course of children with brain injury; it is
      frequently present after surgery for brain tumors and hydrocephalus and in
      patients with severe head trauma. Close monitoring of salt and fluid balance is
      essential to prevent severe neurologic and hemodynamic complications.

PMID- 16996400
TI  - Adolescent pertussis-induced partial arousal parasomnia.
AB  - The aim of the study was to assess neurologic complications of pertussis
      infection. A file review of all children (age 7-18 years) in our hospital with
      serology-positive pertussis infection admitted from 1995 to 2005 yielded six
      patients with neurologic symptoms in whom electroencephalographic studies were
      performed. Data were collected on their clinical symptoms,
      electroencephalographic findings, final diagnosis, and outcome. The six patients
      accounted for 10% of all children diagnosed with pertussis during the study
      period. Their ages ranged from 10 to 15.5 years. All the children were referred
      by their primary physician because of a suspicion of epilepsy on the basis of
      parental reports of inefficient attempts to breathe during sleep accompanied by
      high-pitched sounds and sounds of suffocation, and sleepwalking. The children
      were amnesic for the episodes. However, findings on electroencephalogram taken
      during sleep were negative in all cases. The final diagnosis was partial arousal
      parasomnia. The symptoms of parasomnia disappeared with resolution of the
      symptoms of the pertussis infection. In conclusion, partial arousal parasomnia
      may be induced by pertussis infection. Further studies in larger groups are
      required to confirm this association.

PMID- 16996401
TI  - Teenage outcome after being born at term with moderate neonatal encephalopathy.
AB  - The aim of this study was to assess cognitive functions and behavior problems in
      teenagers who survived moderate neonatal encephalopathy and did not develop
      cerebral palsy. The study population comprised all 97,468 individuals born in
      Sweden in 1985. Of these, 684 (0.7%) were born at term and had an Apgar score of
      <7 at 5 minutes. The obstetric and neonatal records were scrutinized and the
      individuals were classified according to degree of neonatal encephalopathy.
      Teenagers with moderate neonatal encephalopathy without cerebral palsy and other
      major neuro-impairments were subjected to a clinical assessment including
      interviews, neuropsychological tests, and assessments of data from records. Age
      at examination was 15-19 years. Fifty-six individuals who had moderate neonatal
      encephalopathy were identified. Thirteen (23%) had parents who declined
      participation in the study. Of the remaining 43 subjects, 15 (30%) had a
      diagnosis of cerebral palsy or other major neuro-impairments and 28 had no such
      impairments. The latter group was examined, 20 of whom (71%) had definite
      cognitive dysfunctions. Five (18%) had hearing impairments. Only eight teenagers
      were without impairments. Of those who did not have cerebral palsy, the majority
      had cognitive/executive problems that interfered with their daily life situation.
      Clinical follow-up, including assessments of cognitive functions before school
      start, should be considered for all individuals in this high-risk group.

PMID- 16996402
TI  - Ginkgo nut intoxication in a 2-year-old male.
AB  - This report describes a case of ginkgo nut intoxication in a 2-year-old male. The
      patient presented with vomiting and afebrile convulsion 4 hours after eating a
      large number of roasted gingko nuts. There was a large volume of ginkgo nuts in
      his vomited matter, and on admission the concentrations of 4-O-methoxypyridoxine
      in his serum and urine were elevated. The patient was diagnosed as having ginkgo
      nut intoxication, and diazepam and pyridoxal phosphate were administered
      intravenously. After the treatment, his symptoms were resolved. The neurotoxicity
      of ginkgo nuts should be recognized by pediatricians and parents who have
      infants.

PMID- 16996403
TI  - Anti-GT1a IgG antibodies in a child with severe Guillain-Barre syndrome.
AB  - This report describes a male, age 8 years 10 months, with severe Guillain-Barre
      syndrome after Campylobacter jejuni infection. The patient developed fulminant
      muscle weakness, external ophthalmoplegia, bulbar palsy, and respiratory
      distress. A high level of serum monospecific anti-GT1a immunoglobulin G antibody
      was detected. He was treated with intravenous immunoglobulins and artificial
      ventilation. Two years after the onset, the patient still suffered from residual
      leg weakness and foot drop. After 3 years and clinical recovery, the antibody was
      no longer detectable. This report presents the first case in childhood suggesting
      an association between a severe Guillain-Barre syndrome after C. jejuni enteritis
      with monospecific anti-GT1a immunoglobulin G antibody.

PMID- 16996404
TI  - Idiopathic granulomatous encephalitis mimicking malignant brain tumor.
AB  - Idiopathic granulomatous encephalitis is a rare disorder of unknown etiology,
      undetermined treatment, and often grave prognosis. This article describes a 4
      year-old female who presented with a single focal febrile convulsion followed a
      few weeks later by right-sided hemiparesis. A huge infiltrative cerebral mass
      tumor was found which proved to be a granuloma on histologic study. Despite a
      thorough evaluation, including tissue studies and search for an infectious agent,
      no etiology could be identified, and the final diagnosis was idiopathic
      granulomatous encephalitis. Recurrent resections and high-dose steroid treatment
      failed to control the process, and the patient died of disease 6 months after
      presentation. Evaluation and treatment of idiopathic granulomatous encephalitis
      should be aggressive, and the possibility of chemotherapy and perhaps even
      radiotherapy should be considered if there is no response to steroids.

PMID- 16996405
TI  - Psychological presentations without hepatic involvement in Wilson disease.
AB  - Wilson disease is an autosomal recessive inborn error of copper metabolism that
      leads to neurologic symptoms and variable degrees of hepatic damage. The most
      common characteristic signs clinically are liver disease, psychiatric disease,
      neurologic disease, or a combination of these. Early recognition by means of
      clinical signs and an early initiation of therapy using chelators or zinc-salts
      are essential for a good outcome and prognosis. This report describes a male
      suffering from Wilson disease who exhibited an unusual presentation that included
      psychological manifestations without hepatic involvement. He was initially
      treated for attention-deficit hyperactivity disorder and a seizure disorder until
      brain imaging established the diagnosis of Wilson disease.

PMID- 16996406
TI  - Ataxia-telangiectasia complicated by craniopharyngioma--a new observation.
AB  - Ataxia-telangiectasia is a rare autosomal recessive neurodegenerative disorder
      with high incidence of malignancy including leukemias, lymphomas, and solid
      tumors. Central nervous system tumors in ataxia telangiectasia include
      medulloblastomas and gliomas. We describe a 13-year-old girl with ataxia
      telangiectasia who developed craniopharyngioma and non-Hodgkin's lymphoma. To our
      knowledge, this is the first case of ataxia telangiectasia complicated by
      craniopharyngioma in the English literature.

PMID- 16996407
TI  - Normal muscle respiratory chain enzymes can complicate mitochondrial disease
      diagnosis.
AB  - This report presents a case of mitochondrial respiratory chain deficiency in a
      neonate with elevated plasma lactate, hypotonia, developmental delay, and
      dysmorphic features. The initial biochemical analyses of muscle tissue for
      mitochondrial function were normal. Additional testing on skin fibroblasts
      performed owing to a high clinical suspicion of a possible mitochondrial disorder
      indicated a deficiency of mitochondrial complex I. Western blotting of samples
      obtained both from muscle and fibroblast tissues also revealed an extensive
      defect in mitochondrial respiratory chain complex I, confirming the diagnosis.
      These observations underscore the fact that both enzymatic and immunological
      assays should be undertaken in alternate tissues when muscle biopsies are
      inconclusive in highly suspected cases.

PMID- 16996408
TI  - Early mitochondrial dysfunction in an infant with Alexander disease.
AB  - Alexander disease is a neurodegenerative disorder characterized by macrocephaly
      and progressive demyelination with frontal lobe preponderance. The infantile
      form, the most frequent variant, appears between birth and 2 years of age and
      involves a severe course with a rapid neurologic deterioration. Although magnetic
      resonance imaging is useful for diagnosis, currently diagnosis is confirmed by
      the finding of missense mutation in the glial fibrillary acidic protein (GFAP)
      gene. This case reports a female who presented at the age of 5 months with
      refractory epilepsy and hypotonia. Laboratory examinations, muscle biopsy
      examination, and energetic metabolic study in muscle indicated increased
      concentrations of lactate, mitochondria with structural abnormalities, and
      decreased cytochrome-c oxidase activity respectively. Later, both clinical course
      and magnetic resonance findings were compatible with Alexander disease, which was
      confirmed by the finding of a novel glial fibrillary acidic protein gene
      mutation.

PMID- 16996409
TI  - Postencephalitic chronic granulomatous disease.
AB  - This report details the evolution of a case of herpes simplex encephalitis to
      chronic granuloma in a 13-year old female who, at the age of 8, suffered herpes
      simplex virus type 1 encephalitis. Eight months later, she developed an
      intracranial hypertension syndrome with the onset of a new lesion in the necrosed
      zone of her right temporal lobe, with no viral presence in the cerebrospinal
      fluid. The histologic characteristics were those of chronic granuloma with
      multinucleated giant cells and calcifications. Initially treated for
      neurosarcoidosis, the patient remained steroid-dependent for 4 years and the
      steroids could only be withdrawn by treatment with Infliximab. This type of
      evolutive pattern has probably been completely overlooked until now; it can only
      be accurately diagnosed by biopsy. It was initially mistaken for
      neurosarcoidosis.

PMID- 16996410
TI  - Myostatin expression in muscular dystrophies and mitochondrial
      encephalomyopathies.

PMID- 16996413
TI  - Principles and devices.
AB  - The development of catheter-based ultrasound imaging began in the 1950s using
      large-diameter catheters and frequencies of between 1 and 10 MHz. In the 1970s,
      360 degrees cross-sectional imaging of vessels was reported using multi-element
      or phase-array transducers. Since then, refinements in imaging frequency,
      catheter size, image quality, and computer-driven imaging platforms have
      transformed intravascular ultrasound (IVUS) from predominantly a research tool to
      an important clinical intervention.

PMID- 16996414
TI  - Intravascular ultrasound in the coronary arteries.
AB  - With technical improvements in catheter designs, intravascular ultrasound (IVUS)
      imaging of coronary arteries has become a routine procedure in most cardiac
      catheterization laboratories. In clinical practice, IVUS imaging of the coronary
      arteries is commonly performed to answer specific clinical questions such as the
      evaluation of an indeterminate narrowing of the left main coronary artery. In
      recent years, IVUS is also being performed as an endpoint for drug treatment
      trials in the assessment of atherosclerosis progression and/or regression. In
      this review we will focus on how validation studies of coronary IVUS systems have
      advanced our ability to use this powerful imaging tool and understand IVUS
      images, how acoustic and geometric factors affect proposed image processing tools
      and illustrate some current clinical uses of coronary IVUS.

PMID- 16996415
TI  - Applications of intravascular ultrasound in the treatment of peripheral occlusive
      disease.
AB  - Intravascular ultrasound (IVUS) has emerged as a useful and often necessary
      adjunct in a rising number of catheter-based peripheral interventions. IVUS
      catheters enable luminal and transmural cross-sectional imaging of peripheral
      vessels with high dimensional accuracy and provide detailed information about
      lesion morphology. IVUS is able to guide the optimal choice of appropriate
      angioplasty technique, guide the delivery of endovascular devices, and assess the
      immediate outcome of an intervention. In this review we discuss the role of IVUS
      for peripheral occlusive diseases, specifically the application of IVUS
      technology during percutaneous transluminal angioplasty (PTA), intravascular
      stent placement, crossing total occlusions, and venous obstructive disease.

PMID- 16996416
TI  - Intravascular ultrasound use in the treatment of thoracoabdominal dissections,
      aneurysms, and transections.
AB  - Intravascular ultrasound (IVUS) has become an important adjunct in the
      endovascular treatment of thoracoabdominal aortic pathology. In this article, we
      hope to describe and define the expanding role of IVUS as a tool for the vascular
      surgeon in the treatment of thoracoabdominal aortic dissections, aneurysms, and
      transections. IVUS is of particular benefit in the treatment of aortic
      dissections and aortic transections.

PMID- 16996417
TI  - Intravascular ultrasound-guided bedside placement of inferior vena cava filters.
AB  - Pulmonary emboli in a critically ill patient population is an occurrence that may
      be reduced with appropriate utilization of inferior vena cava (IVC) filters.
      Complications both during transfer or transport of critically ill patients who
      are dependent upon multiple intravenous drips, ventilators and intensive
      monitoring may be reduced with bedside placement of inferior vena cava filters.
      Over the last decade, investigators have been developing techniques for bedside
      IVC filter placement based on intravascular ultrasound techniques. We discuss and
      detail a single venous access technique of IVC filter placement using
      intravascular ultrasound.

PMID- 16996418
TI  - Virtual histology and color flow intravascular ultrasound in peripheral
      interventions.
AB  - The quality and interpretation of intravascular ultrasound (IVUS) imaging has
      been revolutionized in recent years by two new and major advances: virtual
      histology and color flow IVUS. Virtual histology intravascular ultrasound
      (VHIVUS) is a catheter-based technology where IVUS is generated from the
      transducer on the catheter tip and the reflected signals from the artery wall
      produce a color-coded map of the arterial disease. Different histological
      constituents of the plaque produce different reflected signals and these are
      assigned different colors (dark green, fibrous; yellow/green, fibrofatty; white,
      calcified; red, necrotic lipid core plaque). This color-coded map assists the
      interventionalist in understanding more fully how the lesion will behave at the
      moment of treatment, whether it will resist complete stent deployment or be
      liable to embolization. Originally introduced for coronary interventions, VHIVUS
      is now being applied to peripheral situations. Because it provides a detailed and
      close-proximity view of plaque, its potential to improve the safety and efficacy
      of carotid endoluminal repair is stimulating substantial interest. Similarly,
      color flow IVUS provides greater understanding for the operator of blood flow,
      and the interface between the vessel wall and the blood stream, lumen size, and
      success of treatment. Color flow IVUS does not use the Doppler effect, but
      creates real-time images that resemble color flow Doppler ultrasound. These two
      technological advances in IVUS have greatly improved the ability of the
      endovascular specialist to understand the arterial disease they are treating and
      to assess the completion of treatment.

PMID- 16996420
TI  - Traumatic brain injury: a primer for primary care physicians.

PMID- 16996422
TI  - Complications analysis of 266 immediate breast reconstructions.
AB  - The purpose of this study was to describe the complications of immediate breast
      reconstruction, to compare their rates with respect to the surgical procedure and
      to patient's characteristics, in order to improve surgical indications and
      patient information. We carried out a retrospective study of 266 immediate breast
      reconstructions (249 women) over a 12-year period (latissimus dorsi myocutaneous
      flap with implant 61%, autologous latissimus dorsi myocutaneous flap 15%,
      subpectoral implant 24%). Mean age was 48 and the median follow-up was seven
      years (2-14). The overall complication rate was 49% (128), and there were 10
      reconstruction failures. The most frequent complications were dorsal seroma 26%
      (70), capsular contracture 10% (27), skin necrosis 8.3% (22), and haematoma 5.6%
      (15). The complication rate for immediate breast reconstruction with implant
      alone (39%) was lower than that associated with latissimus dorsi with or without
      implant (51%), but the difference was not significant (Chi-square: p=0.07). The
      risk factors for complications were smoking (skin necrosis, Fisher: p=0.02),
      obesity (infection, Fisher: p=0.004), and radiotherapy (capsular contracture, Chi
      square: p=2.6 x 10(-5)). Smoking was found as the only risk factor of
      reconstruction failure (Fisher: p=0.015). Capsular contractures were more
      frequent when implants were used alone (25%) as well as when used along with a
      flap (6.8%) (Chi-square: p=2 x 10(-5)). Infections were also higher in the non
      flap group than in the flap group (Fisher: p=0.02). In our opinion, latissimus
      dorsi myocutaneous flap with or without an implant is a good compromise between
      complication risk and necessity of good cosmetic result requirement. These
      results have led us to delay or contraindicate reconstruction in the case of
      obesity or heavy smoking. In the case of probable post-operative radiotherapy, we
      prefer to delay the breast reconstruction.

PMID- 16996423
TI  - Envelope mastectomy and immediate reconstruction (EMIR), improving outcome
      without oncological compromise.
AB  - AIM: To determine the long term oncological safety and aesthetic acceptability of
      envelope mastectomy and immediate reconstruction (EMIR). PATIENTS AND METHODS: A
      retrospective review of 71 cases was carried out. Oncological assessment was by
      clinical examination, mammography, ultrasound, and, where indicated, MRI scan.
      Aesthetic assessment was based on detailed clinical examination as well as
      subjective self-assessment of the outcome. RESULTS: During follow-up (mean 48
      months), there were three local recurrences, only one involving the nipple
      areolar complex. The mean aesthetic score was 0.75 (out of 1), representing a
      good aesthetic outcome and patient satisfaction. CONCLUSION: Nipple-areolar
      complex preservation is a safe option and EMIR produced a good aesthetic outcome,
      which is oncologically safe. Furthermore, it does not preclude post-operative
      radiotherapy.

PMID- 16996424
TI  - Free DIEAP and SGAP flap breast reconstruction after abdominal/gluteal
      liposuction.
AB  - Perforator flaps are widely used in our unit for breast reconstruction. They
      provide ample tissue with minimal donor site morbidity together with long lasting
      aesthetic results. Increasing number of patients may have liposuction procedure
      which may jeopardise areas such as the abdomen and the buttock which are the
      donor sites for perforator-free flaps in breast reconstruction. Therefore,
      liposuction has been considered as a relative contraindication of raising
      perforator flaps. Six patients who had previous liposuction of the donor sites
      underwent autologous breast reconstruction with perforator-free flaps. Colour
      Duplex imaging was obtained in all cases preoperatively in order to evaluate the
      blood supply to the flap and to map the perforators. There were five deep
      inferior epigastric artery flaps (DIEP) and one superior gluteal artery
      perforator (SGAP) flap used. Total flap survival was obtained in all cases.
      Postoperative course was uneventful. Our results showed that raising perforator
      flaps after liposuction of the donor sites is possible. Preoperative radiological
      evaluation of the perforators is mandatory for such difficult cases.

PMID- 16996425
TI  - One-stage breast reconstruction using McGhan Style 150 biodimensional expanders:
      a review of 107 implants with six years experience.
AB  - Permanent expanders have revolutionised breast reconstructive surgery, allowing
      one-stage procedures and the development of increasingly sophisticated implants
      (textured, anatomically shaped) has played an important role in enhancing the
      aesthetic outcomes. It is important to evaluate the tolerability of the implant.
      The aim of this present study was to evaluate the survival curves for McGhan
      Style 150 permanent expanders, in a consecutive series of breast reconstructions.
      Complications rates were also examined. Between April 1997 and May 2003, 107
      McGhan Style 150 expanders (either full height or short height depending on
      patients' requirements) were used in 97 consecutive patients for a variety of
      breast reconstructive procedures. Overall, 46 devices were used for immediate
      reconstruction, 15 for delayed reconstruction and 46 for implant exchange,
      respectively. The mean age at implantation was 48 years (min: 26; max: 71). The
      mean follow-up was 60 months (min: 12; max: 72). Explantation was considered the
      most objective outcome variable, therefore this parameter was carefully monitored
      and then analysed using the Kaplan-Meier method of survival analysis. Different
      curves were compared using the log-rank test. Long term complications were also
      recorded. Among complications the most frequent finding was Baker 3-4 capsular
      contracture, occurring in 26% of immediate reconstructions at six years.
      Explantations increased in an almost linear fashion, with an overall rate of 25%,
      with a statistically significant difference among immediate reconstruction group
      and the implant exchange group. The rate of explantations was high, if compared
      with other series, because the sample included patients undergoing strong
      adjuvant therapies, particularly in the immediate group (locally advanced
      disease). The overall rate of explantations and of capsular contracture was found
      to be significantly lower in the delayed and substitution groups, than the
      immediate group (p<0.05). In our hands, the McGhan Style 150 anatomically shaped
      permanent expanders were associated with acceptable results, especially when used
      as 'permanent prostheses' for second stage procedures.

PMID- 16996426
TI  - The influence of radiotherapy on capsule formation and aesthetic outcome after
      immediate breast reconstruction using biodimensional anatomical expander
      implants.
AB  - BACKGROUND: Capsular contracture occurs more frequently when immediate breast
      reconstruction (IBR) is associated with radiotherapy (RT) in a post-mastectomy
      field. The aim of this study was to investigate the impact of RT on surgical
      outcome after IBR using a single implant type. METHODS: One hundred and thirty
      six breast reconstructions were studied in 114 patients: 62 reconstructions were
      performed using submuscular implants alone and 74 had an implant-assisted
      latissimus dorsi myocutaneous flap using a McGhan 150 biodimensional permanent
      expander implant. Data were prospectively collected on capsule contracture,
      geometric measurements, photographic assessments and pain scores. The median
      follow-up was 4 (range, 2-5) years. RESULTS: The mean age of the 114 patients
      studied was 45 (range, 20-77) years. Forty-four reconstructed breasts received
      RT. Capsule formation was detected in 13/92 (14.1%) reconstructed breasts with no
      RT and in 17/44 (38.6%) reconstructed breasts with RT. On univariate analysis, RT
      was the only variable related to capsule formation (p<0.001). Significant
      differences in geometric measurements of symmetry were identified in patients
      with capsules compared with those without capsules. Photographic assessments were
      worse in the capsule group: mean photo score 8 (95% CI 8, 8.5) compared with the
      no capsule group 6.5 (95% CI 5, 7.5), p<0.001. Persistent pain two years or more
      after surgery was present in 8/30 patients with capsules and 1/106 with no
      capsule group, p<0.01. Capsule formation is three times more likely to occur
      after IBR in association with an RT field. However, as more than 60% of patients
      do not get capsules despite RT at four years, implant-assisted tissue expansion
      techniques using a biodimensional device is a viable breast reconstructive option
      in selected cases.

PMID- 16996427
TI  - Tattooing of the nipple-areola complex: review of outcome in 40 patients.
AB  - Reconstruction of a pigmented nipple-areola complex (NAC) is one of the final
      steps in rehabilitating patients following mastectomy. We report the results of
      40 consecutive patients who had NAC tattooing done by the same surgeon.
      Assessments were made both subjectively using a questionnaire, and objectively by
      using a computer software programme (Adobe Photoshop) to analyse the colour of
      the NACs. Follow up ranged between six and 24 months (mean 14 months). One
      patient suffered an infection, and was the only one to need repeat tattooing in
      our series. Thirty-seven patients (92%) reported some colour fading which ranged
      between 5% and 80% (mean 32%). A grade of good or very good was given by 33
      patients (82%) for colour match, by 36 patients (90%) for over all satisfaction,
      and by 34 patients (85%) for enhancement in body image. An analysis of the
      colours of the tattooed and unoperated NACs by the software programme showed that
      they were similar to a value that ranged from 78% to 97% (mean 91%). Tattooing is
      a simple and safe procedure, and despite some colour asymmetry it still has a
      high satisfaction rate. It significantly improves patient's perception of body
      image. An objective assessment of tattooing using a computer software programme
      can be a useful tool in reviewing the outcome. Video clips (1-5) are included
      with the paper for demonstration of the tattooing technique (re-arranged from the
      video presented with the paper at BAPS).

PMID- 16996428
TI  - The patient's experience of a nurse-led nipple tattoo service: a successful
      program in Warwickshire.
AB  - INTRODUCTION AND AIMS: Although once the preserve of tattoo artists, units within
      the UK have increasingly begun making use of the Clinical Nurse Specialist (CNS)
      to perform areola tattooing. Bringing the technique within the Breast Unit
      enhances continuity of care and makes use of skills that can be provided by the
      CNS. Our CNS is involved with both the patients' oncological management and the
      areola tattoo service. MATERIALS AND METHODS: The CNS-led service was
      investigated and patients' experiences of nipple tattooing were assessed. We
      present the results of a postal questionnaire and a prospective clinical audit of
      the procedure. RESULTS: Forty tattoos were done over a 2-year period with one
      self-limiting complication. Patient satisfaction was high both with the outcome
      and the experience of the procedure. Fading of the tattoo is a consistent finding
      frequently requiring further shading. CONCLUSION: Overall the patient's
      experience of a nurse lead 'in-house' tattoo service has been highly satisfactory
      and this is reflected by their high confidence rating and ease of access to the
      nurse. We believe that the role of the CNS in oncological treatment and
      reconstructions helps integrate the multidisciplinary experience for the patient.

PMID- 16996429
TI  - Long-term nipple shrinkage following augmentation by an autologous rib cartilage
      transplant in free DIEP-flaps.
AB  - Aesthetically pleasing nipple-areola reconstruction is a satisfying part of a two
      stage breast reconstruction. The up to 50% [Banducci DR, Le TK, Hughes KC. Long
      term follow-up of a modified Anton-Hartrampf nipple reconstruction. Ann Plast
      Surg 1999;43(5):467-9; discussion 469-70] postoperative shrinkage following a
      conventional nipple reconstruction is a well-known problem. Augmentation of the
      nipple with autologous banked cartilage seems to be a promising solution. From
      2000-2003, 17 patients underwent a nipple-areola-complex reconstruction following
      secondary breast reconstruction using free perforator flaps. The rib cartilage
      harvested during the preparation of the internal thoracic vessels was banked
      subcutaneously and six months later replanted under the 'arrow flap' after
      contouring it in a 'mushroom' shape. One year later the shrinkage of the nipple
      in comparison to the intraoperative status was measured. In addition, patients
      were asked about their personal palpation impression and the aesthetic outcome.
      The average height decreased one year postoperatively about 25%. Thirteen of 17
      patients judged the aesthetic outcome as very good, 16 nipples healed without
      cartilage protrusion and no patient felt discomfortable stiffness of the nipple.
      Our concept of a nipple augmentation with rib cartilage improves the projection
      and allows a more correct judgement of the later nipple shrinkage. We consider
      this technique to be an aesthetically satisfying and safe method, which could be
      used with any kind of breast reconstruction.

PMID- 16996430
TI  - Mammaplasty: the 'Modified Benelli' technique with de-epithelialisation and a
      double round-block suture.
AB  - Benelli in 1990 demonstrated the round-block technique in mammaplasty to confine
      the scar in the areola. However, problems of scar widening and changes in areola
      shape represent a common problem with this technique. We present a modification
      to the technique that preserves the shape of the areola without the need for a
      non-absorbable suture. This technique may also be used to reduce the areola
      diameter.

PMID- 16996431
TI  - Large fasciocutaneous perforator based V-Y advancement flap for large post
      mastectomy wound reconstruction--our experience with three cases.
AB  - Old and frail patients with advance breast malignancy require mastectomy which
      often results in large defects requiring soft tissue cover. We present three
      cases of large fasciocutaneous perforator based V-Y advancement flaps for
      reconstruction of large post-mastectomy wounds in older patients with large
      tumours. This technique reduces the morbidity of patients who have severe co
      existing morbidity factor in addition to the advance breast disease.

PMID- 16996432
TI  - Endoscopic transaxillary subpectoral augmentation mammaplasty: a safe and
      predictable procedure.
AB  - During the last decades breast augmentation has gained worldwide acceptance. In
      addition to the inframammary and periareolar approach for augmentation
      mammaplasty, the transaxillary route provides an elegant means of retaining the
      integrity of the breast mound by avoiding visible scars. Due to concerns as to
      the safety of this technique we analysed 47 patients who underwent endoscopy
      assisted transaxillary submuscular augmentation mammaplasty in our department
      from 1999 to 2004. The inclusion criteria were aesthetic breast augmentation due
      to breast hypoplasia. Patients with a history of breast cancer, other
      malignancies, or previously performed mastectomy were excluded. Procedures for
      tuberous breast deformity as well as concomitantly performed mastopexy were also
      excluded. No complications were observed impairing final outcome or requiring
      early operative intervention, such as infection or haematoma. This technique is
      suitable for patients who prefer a hidden incision at a distant site, and
      provides predictability of aesthetic outcome and is safe.

PMID- 16996433
TI  - Reconstruction of pectus excavatum with silicone implants.
AB  - The pectus excavatum deformity is characterised by a deep depression usually
      involving the lower one-half to two-thirds of the sternum. The indications for
      surgery are often aesthetic. Extensive procedures, requiring fracturing and
      remodelling of the chest wall skeleton are associated with high morbidity and
      high rate of complications. In this article we describe our renewed experience
      with reconstruction of mild and moderate pectus excavatum deformities with custom
      made prefabricated silicone implants. The fabrication of the implant and the
      surgical technique are described in detail. An excellent aesthetic correction of
      the deformity was achieved in all of the patients in our series, with high
      patient satisfaction rate. We conclude that with careful patient selection,
      artistic implant fabrication and meticulous surgical technique, this approach
      achieves excellent aesthetic correction with minimal morbidity and a low
      complication rate and therefore should maintain its place in the armamentarium of
      surgical techniques for reconstruction of pectus deformities.

PMID- 16996434
TI  - The treatment of sulphur mustard burns with laser debridement.
AB  - The chemical warfare agent, sulphur mustard (SM), is a potent blistering agent in
      man. Skin exposure can produce partial-thickness burns which take up to three
      months to heal. The aim of this study was to investigate the use of early laser
      ablation as a means of accelerating this exceptionally slow rate of healing. Four
      circular partial-thickness SM burns were induced on the dorsum of nine large
      white pigs (under general anaesthesia). At 72 h post-exposure, three burns per
      animal were ablated with a single pass of an UltraPulse 5000C CO(2) laser, at a
      fluence of 5-6 J cm(-2). All the burns were dressed with silver sulphadiazine and
      a semi-occlusive dressing. At one, two and three weeks post-surgery three animals
      were culled and all lesions excised for histological analysis. Burn depth was
      confirmed and measurements of the radii of regenerative epithelium were performed
      allowing the area of the zone of re-epithelialisation in each lesion to be
      calculated. Laser-treated lesions showed a significant increase (350%) in healing
      rates compared to controls (p<0.005). At two weeks, the laser-treated sites were
      95% healed in comparison with control sites (28% healed). These data suggest that
      laser ablation may be effective in the treatment of partial-thickness SM-induced
      skin injury.

PMID- 16996435
TI  - The 'expansile' supraclavicular artery flap for release of post-burn neck
      contractures.
AB  - Soft tissue defects in the cervico-facial region can result from trauma, tumour
      excision or post-burn scarring. All rungs of the reconstructive ladder offer
      possible reconstructive options for these defects. The supraclavicular artery
      based flap is an extremely reliable local flap for this purpose. It offers thin
      and pliable skin with good colour match and minimal donor site morbidity. An
      additional advantage, in our experience, is that this skin can stretch
      postoperatively to allow further improved neck contour and mobility. MATERIALS
      AND METHODS: Between June 2000 and January 2004, 27 patients underwent
      reconstruction of neck defects after release of post-burn contractures with the
      supraclavicular artery based skin flap at our hospital. After discharge the first
      follow-up visit was on the 10th postoperative day. The patients were advised to
      wear a custom made Watusi splint for 3 to 4 months. The patients were
      subsequently followed up at 3 months, 6 months and 1 year. The dimensions of the
      flap were measured and the patients photographed at the time of discharge and at
      subsequent visits. RESULTS: All the flaps survived completely. The average
      operating time for contracture release and flap coverage was 2 h. The hospital
      stay ranged from 5 to 8 days. Follow-up ranged from 1 to 4 years with an average
      of 22 months. Complications included epidermolysis (n=2) and delay in donor site
      healing (n=2). Almost all patients had some widening of the donor site scar. In
      our experience the width of the flap increased in the postoperative period. At
      the time of surgery, the width of the flap ranged between 9 and 12 cm. At the 3
      month follow-up there was an average increase in width of 24.2%. At 6 months, the
      average increase in width was 42.8% of the original flap width. At 1 year the
      average flap expansion was 63% of the original. The length of the flap ranged
      from 18 to 24 cm and generally remained unaltered during follow-up.

PMID- 16996436
TI  - Supragaleal placement of tissue expander for post-burn alopecia.
AB  - Supragaleal placement of tissue expander for management of alopecia of scalp
      excludes tough galeal layer so that easier and faster expansion of scalp may be
      achieved.

PMID- 16996437
TI  - Starplasty: an ideal method for correction of occluded external nares following
      burns.
AB  - Correction of any closed ostium following either burns or any other trauma by
      release and split skin grafting is not very successful in the long run because of
      restenosis of the ostium by contraction of the graft. It is very difficult to
      maintain the patency by any kind of prosthesis. For this reason we have devised a
      new technique called 'starplasty', which is simple and effective in opening
      occluded external nares without any chances of restenosis.

PMID- 16996438
TI  - Corrosive injury of oral cavity--a rare presentation.
AB  - Corrosive injury of the upper gastrointestinal tract has been frequently reported
      in medical literature. The ingestion of acid or alkali may be accidental or
      intentional. The spectrum of injury varies from involving the oesophagus,
      stomach, and duodenum either individually or together. The oral cavity is rarely
      involved. The sequelae of oral cavity caustic injury that have been reported
      include microstomia, shallow vestibule, ankyloglossia, speech impairment, loss of
      teeth and impairment of facial expression. We report a case of corrosive injury
      of the oral cavity following accidental ingestion of caustic alkali, who
      presented to us with bilateral submandibular gland enlargement following the
      development of corrosive stricture of the submandibular ducts. The scar tissue in
      the anterior floor mouth was excised with the submandibular salivary glands.
      Concomitant release of the contracture in the gingivo-buccal sulcus was also done
      and the defect was covered with a radial forearm free flap. The presentation of
      corrosive oral injury as salivary duct obstruction and enlarged salivary glands
      has not been reported. Free tissue transfer for corrosive scarring in the oral
      cavity helps to restore pliable tissue.

PMID- 16996439
TI  - Morphea of the breast. Two case reports and discussion of the literature.
AB  - Morphea, or localised scleroderma, is characterised by excess collagen deposition
      by lesional fibroblasts. This results in thickening and induration of the skin
      and subcutaneous tissues, often causing considerable morbidity. Radiation-induced
      morphea was mentioned as early as the 1900s, but since then awareness of this
      condition has declined. The incidence of radiation-induced morphea is said to be
      two in 1000. Extension of the morphea beyond the radiation ports occurs in
      approximately one quarter of cases. No proven effective treatments exist, and to
      our knowledge, surgical excision has not been attempted. CASE PRESENTATIONS: We
      present two cases of morphea of the breast. The first patient developed
      progressive morphea in the absence of any causative factors. This was treated by
      Wise pattern breast reduction, incorporating the morphea within the excised skin.
      The second patient developed morphea following a course of radiotherapy for
      breast carcinoma. She has declined any surgical intervention, but suffers from
      considerable morbidity. Morphea is a recognised sequelae of radiotherapy which
      should be distinguished from sclerotic recurrence of the original tumour.
      Surgical excision is possible in certain patients.

PMID- 16996440
TI  - The semi-permeability of silicone: a saline-filled breast implant with
      intraluminal and pericapsular Aspergillus flavus.
AB  - Fungal infection of breast implants is a rare complication. Growth of fungi
      within the lumen of saline-filled implants has previously been demonstrated in
      laboratory studies, however, clinical infections are rare. We report a case of
      Aspergillus flavus growth within and around a saline-filled breast implant that
      was inserted 18 months previously. This was successfully treated with implant
      removal and wound irrigation. Possible routes of microbial contamination as well
      as survival mechanisms of organisms within saline-filled implants are discussed.
      This case re-iterates that the silicone envelope of a saline-filled implant is
      selectively permeable and we believe this is instrumental in facilitating
      intraluminal microbial growth. This also emphasises the importance of stringent
      asepsis when dealing with saline-filled breast implants including avoiding
      contamination of the saline filling fluid.

PMID- 16996441
TI  - Bilateral inferior oblique palsies following botulinum toxin injections to the
      frontalis muscle.

PMID- 16996442
TI  - Use of henna as a skin marker.

PMID- 16996443
TI  - Post-surgical hypertrichosis.

PMID- 16996444
TI  - A simple hair fixation technique for face lift surgery.

PMID- 16996445
TI  - Familial pseudo pseudoxanthoma elasticum.

PMID- 16996446
TI  - Laxative-induced burns in a child.

PMID- 16996447
TI  - Camouflaging of motor signs in carpal tunnel syndrome.

PMID- 16996448
TI  - Ulnar artery aneurysm in a patient with Marfan's syndrome.

PMID- 16996450
TI  - Interaction of phenosafranine with nucleic acids and model polyphosphates. I.
      Self-aggregation and complex formation with inorganic polyphosphates.
AB  - Aggregation or phenosafranine in concentrated aqueous solutions and its
      interaction with polyphosphates was Studied by absorption and fluorescence
      spectroscopy. At concentrations > 10(-3) M phenosafranine forms dimers (Kd = 3.8
      x 10(2) l.mole(-1)), which are characterized by a hypsochromic shift of the
      visible and near ultraviolet absorption maxima accompanied by a hypochromic
      effect. No fluorescence could be detected from phenosafranine dimers. Analogous
      spectral changes were observed when a polyphosphate was titrated with
      phenusafranine, which indicated that with increasing saturation of the
      polyphosphate binding sites phenosafranine gradually became bound in the
      aggregated form. Full saturation of the polyphosphate binding sites with
      phenosafranine was reached only when an excess of free dye was present. The
      cooperative binding of phenosafranine to a polyphosphate could be evaluated by
      means of a theory proposed by Schwarz et al. At the zero ionic strength and at 25
      degrees C the binding was characterized by cooperative binding constant K = 6.2 x
      10(5) l.mole(-1), number of binding sites per monomeric phosphate residue g =
      0.4, and cooperativity parameter q reverse similar 30. Spectroscopic properties
      of phenosafranine in the aggregated and poly phosphate-bound stotes were compared
      with those of ethidium bromide.

PMID- 16996451
TI  - An electron spin resonance study of high spin forms of cobalt(II) bovine carbonic
      anhydrase.
AB  - The ESR spectra of bovine Co(II) carbonic anhydrase at 7 K at low and high pH and
      of the iodide derivative have been analyzed. The spectrum of the low pH form
      shows axial symmetry whilst that at high pH is rhombically distorted. This
      anisotropy is still more accentuated in the iodide derivative. The high pH
      (hydroxyl) form and the iodide derivative are thought to have a tetracoordinate
      trigonal pyramidal structure, with a fifth more distant axial ligand. The low pH
      form is consistent with a pseudotetrahedral geometry previously postulated.

PMID- 16996452
TI  - Some properties of allophycocyanin from a thermophilic blue-green alga.
AB  - Allophycocyanin was purified from the extremely thermophilic blue-green alga
      Synechococcus lividus. It was shown to be more stable to thermal or urea
      denaturation than allophycocyanin from a mesophilic organisms. Its amino acid
      composition and spectroscopic response to pH were investigated. An analysis was
      made of the relatively low fluorescence polarization of allophycocyanin compared
      to that of a comparable sized aggregate of the biliprotein, C-phycocyanin. A
      rather speculative conclusion was reached that suggests that the lower
      polarization of allophycocyanin may be caused by orientations or positioning of
      the chromophores that are more favorable for intra-protein energy transfer.

PMID- 16996453
TI  - Eighty hour work reform: faculty and resident perceptions.
AB  - OBJECTIVE: The purpose of the study was to describe resident and faculty
      perceptions on the impact of the 80 hour work reform on residency training. STUDY
      DESIGN: Surveys were distributed to resident and faculty at a major university
      based teaching institution. All responses were anonymous. Information abstracted
      from the survey included: demographic characteristics and resident and faculty
      perceptions on resident education, patient care, resident work environment, and
      quality of life after the institution of new regulations on resident duty hours.
      Descriptive and comparison analyses were performed. RESULTS: Ninety-four
      residents and 56 faculty members responded. Significant differences were detected
      in resident and faculty perceptions that work reform improved resident education
      (52.3% vs 20.8%, respectively, P < .01), and worsened quality of patient care
      (8.8% vs 45.3%, respectively, P < .01). Both residents (84.4%) and faculty
      (90.7%) agreed that work reform improved resident quality of life. CONCLUSION:
      Faculty and resident perceptions differed on the impact of the work reform on
      patient care and resident education but agreed that it improved resident quality
      of life.

PMID- 16996454
TI  - Bacteriuria in pregnant women with sickle cell trait.

PMID- 16996457
TI  - Effect of Balint training on resident professionalism.
AB  - OBJECTIVE: The study was designed to assess the impact of 6 months of Balint
      training on self- and faculty-assessed measures of professionalism in obstetrics
      and gynecology residents. STUDY DESIGN: Pre- and post-Balint training resident
      self-assessment and pre- and post-training faculty assessment using standard
      professionalism instruments were used to compare the resident Balint group to the
      group that did not participate. Participating residents also completed a
      qualitative assessment of the experience. RESULTS: Residents who participated
      were enthusiastic regarding the value of Balint in promoting self-reflection and
      gaining insight into self- and patient-care issues, both key components of
      professionalism. There were no significant differences in self or faculty
      assessment of professionalism between residents who participated in Balint and
      those who did not. CONCLUSION: Six months of Balint training was successful in
      providing resident education in professionalism, measured by resident self
      report. No differences were detected on 2 measures of professionalism between the
      training and control groups.

PMID- 16996459
TI  - Alfa-fetoprotein and albumin levels together are more predictive of severe fetal
      hydrops.

PMID- 16996460
TI  - Enhanced thrombotic risk in pregnancy and postpartum: association with CRP
      elevation?

PMID- 16996461
TI  - First-trimester screening for trisomy 21 using nuchal translucency and nasal bone
      evaluations in a selected and an unselected population.

PMID- 16996462
TI  - A comparison of an interactive computer-based method with a conventional reading
      approach for learning pelvic anatomy.
AB  - OBJECTIVE: This study was undertaken to assess the impact of interactive,
      computer-based versus conventional, paper-based format in student, resident, and
      fellow learning and retention of anatomy knowledge. STUDY DESIGN: Randomized
      longitudinal cohort design with scores repeated as pre-, post-, and follow-up
      tests. Subjects were randomly assigned to an anatomy module in computer-based (CD
      ROM) format and 1 in paper-based format. A follow-up examination was administered
      3 weeks after the posttest to evaluate retention of knowledge. Tests results were
      analyzed by using Student t tests and analysis of variance. RESULTS: Thirty-nine
      subjects completed all testing. Regardless of instructional method, pretest to
      posttest scores improved (P < .01), and posttest to follow-up test scores
      decreased among all levels of training (P < .01). Student satisfaction was
      highest with CD-ROM format. CONCLUSION: Improvement and retention of anatomy
      knowledge was not significantly different when comparing a new CD-ROM interactive
      approach with a traditional paper-based method.

PMID- 16996464
TI  - Base deficit estimation in umbilical cord blood is influenced by gestational age,
      choice of fetal fluid compartment, and algorithm for calculation.
AB  - OBJECTIVE: The purpose of this study was to explore the influences of gestational
      age, the choice of fetal fluid compartment, and the algorithm for calculation on
      the estimation of the base deficit in umbilical cord arterial blood at birth.
      STUDY DESIGN: From 1995 to 2002, cord arterial blood gases and obstetric data
      were available for 43,551 newborn infants at 37+ weeks of gestation (cohort I).
      The mean base deficit in blood and the base deficit in extracellular fluid were
      estimated from pH and PCO2 values in 28,213 newborn infants with a 5-minute Apgar
      score of > or = 9 (cohort II) with the use of 3 different calculation algorithms
      (base deficit in blood, base deficit in extracellular fluid [A], and base deficit
      in extracellular fluid [B]). RESULTS: In cohort II, the base deficit in blood,
      the base deficit in extracellular fluid (A), and the base deficit in
      extracellular fluid (B) increased with advancing gestational age (linear
      regression; P < .0001). The curves run almost parallel, with the base deficit in
      blood being higher than the base deficit in extracellular fluid (A) and (B). With
      the use of receiver operating characteristic curves in cohort I, the area under
      curve to indicate a 5-minute Apgar score of < 7 and < 4 showed the area under
      curve-pH to be greater than the area under curve-base deficit in extracellular
      fluid (A) and (B), the area under curve-base deficit in blood to be greater than
      the area under curve-base deficit in extracellular fluid (A) and (B) for a 5
      minute Apgar score of < 7, and the area under curve-base deficit in blood to be
      greater than the area under curve-base deficit in extracellular fluid (A) and (B)
      for an Apgar score of < 4. The cutoffs with highest sensitivity and lowest false
      positive rate for a 5-minute Apgar score of < 7 and < 4 were, for both scores, a
      pH value of 7.15, a base deficit in blood of 10 mmol/L, a base deficit in
      extracellular fluid (A) of 8 mmol/L, and a base deficit in extracellular fluid
      (B) of 6 mmol/L. CONCLUSION: The calculated values of the base deficit in
      umbilical cord arterial blood are influenced decisively by gestational age, the
      choice of fetal fluid compartment, and the calculation algorithms that are used.
      The power of the base deficit to indicate neonatal distress depends on the
      choices of fluid compartment and the algorithm that is used to calculate the base
      deficit.

PMID- 16996465
TI  - Bowel symptoms in women planning surgery for pelvic organ prolapse.
AB  - OBJECTIVE: The objective of the study was to measure associations between bowel
      symptoms and prolapse. STUDY DESIGN: Baseline data were analyzed from 322 women
      in the Colpopexy And Urinary Reduction Efforts trial of sacrocolpopexy with or
      without Burch colposuspension. Women completed the Colorectal-Anal Distress
      Inventory and Colorectal-Anal Impact Questionnaire and underwent Pelvic Organ
      Prolapse Quantification. Associations between symptoms and questionnaire scores
      and Pelvic Organ Prolapse Quantification measures were assessed. RESULTS: Mean
      age was 61 +/- 10 years. Pelvic Organ Prolapse Quantification stages were II
      (14%), III (67%), and IV (19%). Colorectal-Anal Distress Inventory symptoms did
      not increase with prolapse stage. Colorectal-Anal Distress Inventory obstructive
      subscale scores were higher in stage II women (median 29 [interquartile range
      8,92] versus 17 [0,33] and 25 [0,38] for stages III and IV, respectively;
      adjusted P = .01). The few statistically significant correlations between
      symptoms and vaginal descent were negative and weak (less than 0.2). CONCLUSION:
      Bowel symptoms and questionnaire scores do not increase with prolapse stage in
      women presenting for sacrocolpopexy.

PMID- 16996466
TI  - Circulating calcitonin gene-related peptide and its placental origins in
      normotensive and preeclamptic pregnancies.
AB  - OBJECTIVE: The present study was designed to determine plasma calcitonin gene
      related peptide concentration in both maternal and fetal circulations in
      normotensive and pre-eclamptic pregnancies and investigate whether placenta is 1
      of its origins. STUDY DESIGN: Maternal blood, cord blood, and villous tissue were
      collected from women in normotensive pregnancies and complicated with pre
      eclampsia. Calcitonin gene-related peptide concentrations were determined by
      radioimmunoassay. Cellular localizations of calcitonin gene-related peptide
      messenger ribonucleic acid and protein expressions in placental villi were
      determined by in situ hybridization and immunohistochemistry. RESULTS: The
      following results were reached: (1) maternal plasma calcitonin gene-related
      peptide concentrations increased with advancing gestation but fell after
      delivery; (2) both maternal and cord plasma calcitonin gene-related peptide
      concentrations were positively correlated with the infant birth weights; (3)
      compared with normotensive pregnancies, calcitonin gene-related peptide levels in
      both maternal and cord plasma decreased in pregnancies with pre-eclampsia; (4) in
      normotensive pregnancies, the plasma calcitonin gene-related peptide of the
      umbilical vein was higher than the umbilical artery, but no significant
      differences between vein and artery in pre-eclampsia; (5) calcitonin gene-related
      peptide messenger ribonucleic acid and protein were expressed by
      syncytiotrophoblast cells and villous vascular endothelial cells in normotensive
      pregnancies, but only weak or absent staining was observed in pre-eclamptic
      placentas; and (6) calcitonin gene-related peptide is secreted by villous tissue
      in explant culture in a time-dependent manner, but less calcitonin gene-related
      peptide was produced by villous tissues from patients with pre-eclampsia.
      CONCLUSION: Calcitonin gene-related peptide may play potential roles in maternal
      hemodynamic adaptation and fetal growth. Decreased circulating calcitonin gene
      related peptide levels may be involved in maternal-fetal pathophysiology of pre
      eclampsia. It is novel that placenta villous tissues might be one of the
      potential sources of calcitonin gene-related peptide during pregnancy.

PMID- 16996467
TI  - Job satisfaction among obstetrician-gynecologists: a comparison between private
      practice physicians and academic physicians.
AB  - OBJECTIVE: Physician job satisfaction has been the subject of much research.
      However, no studies have been conducted comparing academic and private practice
      physician satisfaction in obstetrics and gynecology. This study was undertaken to
      measure satisfaction levels for academic and private practice obstetrician
      gynecologists and compare different aspects of their practice that contributed to
      their satisfaction. STUDY DESIGN: A survey was mailed to randomly selected
      obstetrician-gynecologists in Memphis, TN; Birmingham, AL; Little Rock, AR; and
      Jackson, MS. Physicians were asked to respond to questions concerning
      demographics and career satisfaction. They were also asked to assess the
      contribution of 13 different aspects of their practice in contributing to their
      job selection and satisfaction using a Likert scale. A score of 1 meant the
      physician completely disagreed with a statement regarding a factor's contribution
      or was completely dissatisfied; a score of 5 meant the physician completely
      agreed with a factor's contribution or was completely satisfied. Simple
      descriptive statistics, as well as the 2-sample t test, were used. Likert scale
      values were assumed to be interval measurements. RESULTS: Of the 297
      questionnaires mailed, 129 (43%) physicians responded. Ninety-five (74%)
      respondents rated their overall satisfaction as 4 or 5. No significant difference
      was found between academic and private physicians when comparing overall job
      satisfaction (P = .25). When compared to private practice physicians, the aspects
      most likely contributing to overall job satisfaction for academic physicians were
      the ability to teach, conduct research, and practice variety (P = .0001, P =
      .0001, and P = .007, respectively). When compared with academic physicians, the
      aspects most likely contributing to job satisfaction for private practice
      physicians were autonomy, physician-patient relationship, and insurance
      reimbursement (P = .0058, P = .0001, and P = .0098, respectively). When choosing
      a practice setting, academic physicians found variety, teaching, and research to
      be more important (P = .0027, P = .0001, and P = .0001, respectively). In
      contrast, private practice physicians found autonomy, physician-patient
      relationship, coworkers, and geographic location to be more important (P = .0005,
      P = .0001, P = .0035, and P = .0016, respectively). CONCLUSION: Academic and
      private practice physicians are equally satisfied with their careers. However,
      teaching, research and variety contribute more to academic satisfaction, whereas
      autonomy, physician-patient relationship, and coworkers contribute more to
      satisfaction for the physician in private practice. This study may be used when
      counseling residents concerning their career options.

PMID- 16996468
TI  - Detection of mutations in the beta-globin gene by colorimetric staining of DNA
      microarrays visualized by a flatbed scanner.

PMID- 16996469
TI  - Immobilized DNA hairpins for assay of sequential breaking and joining of DNA
      backbones.
AB  - Immobilized DNA hairpins are exploited in a novel approach to assay DNA ligases
      and nucleases. A fundamental characteristic of the assay is that a fluorophore at
      the remote terminus of the hairpin reports on the integrity of the DNA backbone.
      The functionality of the protocol is confirmed using ATP- and NAD+-dependent DNA
      ligases and the nicking enzyme N.BbvCIA. The assay format is amenable to high
      throughput analysis and quantitation of enzyme activity, and it is shown to be in
      excellent agreement with the more laborious electrophoretic approaches that are
      widely used for such analyses. Significantly, the assay is used to demonstrate
      sequential breaking and rejoining of a specific nucleic acid. Thus, a simple
      platform for biochemically innovative studies of pathways in cellular nucleic
      acid metabolism is demonstrated.

PMID- 16996470
TI  - Evaluation of two methods for generating cRNA for microarray experiments from
      nanogram amounts of total RNA.
AB  - Several methods have been developed for amplification of RNA, making it possible
      to use cDNA microarrays for analysis of samples limited in amount of total RNA.
      The most widely used amplification protocol, the Eberwine method, amplifies RNA
      in a linear manner through in vitro transcription (IVT). However, when starting
      material is limited to nanogram amounts of total RNA, several rounds of
      amplification are necessary, making this method both expensive and labor
      intensive. Amplification by PCR is robust and is able to amplify extremely
      limiting material. However, it is possible that the nonlinear nature of PCR could
      result in reduced reproducibility of the amplification compared with IVT. We have
      evaluated two methods that use a combination of PCR and IVT for amplification of
      nanogram amounts of total RNA. We have compared microarray results obtained by
      these methods with results obtained by two established methods: indirect labeling
      of 20 microg total RNA and Eberwine amplification of 1 microg total RNA. Starting
      from as little as 5 ng of total RNA, both methods yielded results in concordance
      with the Eberwine method.

PMID- 16996471
TI  - [Reconstruction after pancreaticoduodenectomy: Pancreaticojejunostomy or
      pancreaticogastrostomy?].

PMID- 16996472
TI  - Tolerance of shift work.
AB  - This study aimed to explore criteria for shift work tolerance and to investigate
      the relationships between personality traits and states and shift work tolerance.
      Eighty-nine policemen and police women completed a questionnaire, once during
      consecutive night shifts and again during rotating shifts, and their responses
      were used to assess anxiety, emotional control, positive and negative affect,
      health complaints, sleep quality, difficulties in social and domestic life, and
      perceptions about shift work. Both the criteria for tolerance and the
      relationship between tolerance and personality varied according to shift type.
      Night shift tolerance involved four factors--somatic health, flexibility, sleep
      and sleep need--while rotating shift tolerance involved three factors--somatic
      health, flexibility and fatigue. Tolerance of shift work was associated with
      anxiety, repressive emotional style and mood. During night shifts, anxiety was
      the most influential personality factor for the somatic health and sleep
      dimensions of shift tolerance. During rotating shifts, positive and negative
      moods, rather than trait personality factors, were important predictors of the
      somatic health and fatigue shift tolerance dimensions. These results suggest a
      mechanism for more effective matching of workers to suitable shift schedules.

PMID- 16996473
TI  - Physical nature of signal peptide binding to DmsD.
AB  - Here we describe the biophysical characterization of the interaction of the redox
      enzyme maturation protein DmsD with the signal peptide of its target protein,
      DmsA. Isothermal titration calorimetry (ITC), size exclusion chromatography
      (SEC), and an in vitro Far-Western assay is used to show that DmsD binds the twin
      arginine signal peptide from DmsA in the micromolar range and in a 1:1 molar
      ratio. The SEC also shows that there is no oligomerization upon binding. Urea and
      guanidium hydrochloride denaturation profiles demonstrate the stability of DmsD
      and give insights on how electrostatic and hydrophobic interactions are important
      within this binding process. Furthermore, by use of N- and C-terminal fusions of
      DmsA signal peptide to GST, we observe that N-terminal display of the peptide is
      important for binding DmsD. In addition, all the folding forms of DmsD were found
      to bind the DmsA signal peptide as observed with the Far-Western assay.

PMID- 16996474
TI  - Site-directed mutational analysis of structural interactions of low molecule
      compounds binding to the N-terminal 8 kDa domain of DNA polymerase beta.
AB  - We previously reported the mode of inhibition of DNA polymerase beta (pol. beta)
      by long chain fatty acids and a bile acid, involving binding analyses to the N
      terminal 8-kDa DNA binding domain. Here we describe a site-directed mutational
      analysis in which the key amino acids (L11, K35, H51, K60, L77, and T79), which
      are direct interaction sites in the domain, were substituted with K, A, A, A, K,
      and A, respectively. And their pol. beta interactions with a C24-long chain fatty
      acid, nervonic acid (NA), and a bile acid, lithocholic acid (LCA), were
      investigated by gel mobility shift assay and NMR spectroscopy. In the case of
      K35A, there was complete loss of DNA binding activity while K60A hardly has any
      activity. In contrast the other mutations had no appreciable effects. Thus, K35
      and K60 are key amino acid sites for binding to template DNA. The DNA binding
      activities of L11K, H51A, and T79A as well as the wild type were inhibited by NA
      to the same extent. T79A demonstrated a disturbed interaction with LCA. 1H-15N
      HSQC NMR analysis indicated that despite their many similarities, the wild-type
      and the mutant proteins displayed some significant chemical shift differences.
      Not only were the substituted amino acid residues three-dimensionally shifted,
      but some amino acids which are positioned far distant from the key amino acids
      showed a shift. These results suggest that the interaction surface was
      significantly distorted with the result that LCA could not bind to the domain.
      These findings confirm our previous biochemical and 3D structural proposals
      concerning inhibition by NA and LCA.

PMID- 16996475
TI  - Signaling pathways regulating murine cardiac CREB phosphorylation.
AB  - Using the mouse Langendorff heart perfusion model, the signaling pathways that
      regulate cardiac CREB-S133 phosphorylation have been defined. In mouse hearts
      stimulated with isoproterenol (ISO) (10(-8) M), endothelin-1 (ET-1) (10(-8) M),
      and phorbol 12-myristate 13-acetate (TPA) (10(-7) M), CREB-S133 phosphorylation
      was attained only by TPA-treatment. Activation of protein kinase A (PKA) was
      achieved by ISO. ISO- and ET-1-stimulation activated Ca2+/calmodulin-dependent
      kinase II (CaMKII). Protein kinase C (PKC) and p90(RSK) were activated with all
      three stimuli. Inhibition of ERK1/2 with PD98059 (10(-5) M) completely inhibited
      the activation of p90(RSK), but did not block CREB-S133 phosphorylation in TPA
      perfused heart, indicating that PKA, CaMKII, and p90(RSK) do not phosphorylate
      CREB-S133 in the murine heart. PKC activation is signal specific. Analyses of PKC
      isoforms suggest that CREB phosphorylation is mediated by PKC epsilon
      translocating into nucleus only with TPA stimulation. These results, unlike those
      reported in other tissues, demonstrate that cardiac CREB is not a multi-signal
      target.

PMID- 16996476
TI  - Silencing of vanilloid receptor TRPV1 by RNAi reduces neuropathic and visceral
      pain in vivo.
AB  - RNA interference (RNAi) has proven to be a powerful technique to study the
      function of genes by producing knock-down phenotypes. Here, we report that
      intrathecal injection of an siRNA against the transient receptor potential
      vanilloid receptor 1 (TRPV1) reduced cold allodynia of mononeuropathic rats by
      more than 50% over a time period of approximately 5 days. A second siRNA targeted
      to a different region of the TRPV1 gene was employed and confirmed the analgesic
      action of a TRPV1 knock-down. Furthermore, siRNA treatment diminished spontaneous
      visceral pain behavior induced by capsaicin application to the rectum of mice.
      The analgesic effect of siRNA-mediated knockdown of TRPV1 in the visceral pain
      model was comparable to that of the low-molecular weight receptor antagonist
      BCTC. Our data demonstrate that TRPV1 antagonists, including TRPV1 siRNAs, have
      potential in the treatment of both, neuropathic and visceral pain.

PMID- 16996477
TI  - DLPC and SAMe prevent alpha1(I) collagen mRNA up-regulation in human hepatic
      stellate cells, whether caused by leptin or menadione.
AB  - We previously reported that the combination of dilinoleoylphosphatidylcholine
      (DLPC) and S-adenosylmethionine (SAMe), which have antioxidant properties and
      antifibrogenic actions, prevented leptin-stimulated tissue inhibitor of
      metalloproteinase (TIMP)-1 production in hepatic stellate cells (HSCs) by
      inhibiting H2O2-mediated signal transduction. We now show that DLPC and SAMe
      inhibit alpha1(I) collagen mRNA expression induced by leptin or menadione in LX-2
      human HSCs. We found that DLPC and SAMe prevent H2O2 generation and restore
      reduced glutathione (GSH) depletion whether caused by leptin or menadione.
      Blocking H2O2 signaling through ERK1/2 and p38 pathways resulted in a complete
      inhibition of leptin or menadione-induced alpha1(I) collagen mRNA. The inhibition
      of collagen mRNA by DLPC and SAMe combined is at least two times more effective
      than that by DLPC or SAMe alone. In conjunction with the prevention of TIMP-1
      production, the ability of DLPC and SAMe to inhibit alpha1(I) collagen mRNA
      expression provides a mechanistic basis for these innocuous compounds in the
      prevention of hepatic fibrosis, because enhanced TIMP-1 and collagen productions
      are associated with hepatic fibrogenesis and their attenuation may diminish
      fibrosis.

PMID- 16996478
TI  - Marked increase of insulin gene transcription by suppression of the Rho/Rho
      kinase pathway.
AB  - The hallmarks of type 2 diabetes are pancreatic beta-cell dysfunction and insulin
      resistance. It has been suggested that Rho/Rho-kinase is a mediator of insulin
      signaling, and thereby involved in the development of insulin resistance,
      regulation of insulin action, and glucose homeostasis, but the role of Rho/Rho
      kinase in beta-cells remained unknown. The aim of this study was to examine the
      possible role of Rho/Rho-kinase in beta-cell function. Immunostaining showed that
      RhoA was expressed in mature beta-cells, with higher expression observed in beta
      cells of diabetic C57BL/KsJ-db/db mice compared to non-diabetic mice. In
      addition, to examine the functional role of Rho/Rho-kinase in beta-cells, we
      evaluated the effect of Rho-kinase inhibitors on insulin biosynthesis. Northern
      blot analysis showed that insulin mRNA levels were markedly increased by Rho
      kinase inhibitors, Y-27632 and fasudil, in beta-cell-derived HIT-T15 cells.
      Furthermore, using the luciferase reporter gene assay, insulin promoter activity
      was also dramatically increased by Y-27632, which was associated with an increase
      in the insulin mRNA level. These results suggest that suppression of Rho/Rho
      kinase increases insulin promoter activity, which leads to an increase in insulin
      mRNA level. Taken together, Rho/Rho-kinase is activated in beta-cells under
      diabetic conditions and suppression of the Rho/Rho-kinase pathway increases
      insulin gene transcription. These results imply that Rho/Rho-kinase activation is
      involved in the suppression of insulin expression found in diabetes and that
      suppression of the Rho/Rho-kinase pathway could be a useful tool to augment
      insulin gene transcription.

PMID- 16996479
TI  - Subproteomic study of hepatitis C virus replicon reveals Ras-GTPase-activating
      protein binding protein 1 as potential HCV RC component.
AB  - Hepatitis C virus (HCV) RNA synthesis takes place on a detergent resistant
      membrane (DRM) structure. To identify potential cellular proteins related to HCV
      replication complexes (RC), we purified DRMs from HCV subgenomic replicon cells
      and its parental Huh7 cells. The proteins of DRM fractions were separated by two
      dimensional gel electrophoresis and identified by mass spectrometry. Comparing
      with parental Huh7 cells, 60 proteins were up-regulated while 14 proteins were
      down-regulated in HCV replicon cells. Ras-GTPase-activating protein binding
      protein 1 (G3BP1), one of the elevated proteins, was found to be associated with
      HCV NS5B and knockdown of G3BP1 by siRNA in HCV replicon cells significantly
      reduced HCV replication, which may indicate it a potential component of HCV RC.
      These results suggest that HCV viral gene and proteins may regulate the presence
      of host cellular proteins in DRM, ensure appropriate concentrations of
      replication components, and hence control the rates or efficiencies of HCV
      replication.

PMID- 16996480
TI  - Anti-ischemia/reperfusion of C1 inhibitor in myocardial cell injury via
      regulation of local myocardial C3 activity.
AB  - C3 is common to all pathways of complement activation augmenting
      ischemia/reperfusion (I/R)-induced myocardial injury and cardiac dysfunction.
      Complement inhibition with the complement regulatory protein, C1 inhibitor
      (C1INH), obviously exerts cardioprotective effects. Here, we examine whether
      C1INH regulates C3 activity in the ischemic myocardial tissue. C1INH markedly
      suppressed C3 mRNA expression and protein synthesis in both a model of I/R
      induced rat acute myocardial infarction (AMI) and the cultured rat H9c2 heart
      myocytes. At least, this regulation was at the transcriptional level in response
      to oxygen tension. In vitro, C3 deposition on, and binding to, the surface of rat
      myocardial cells were significantly blocked by C1INH treatment. C1INH could
      inhibit classical complement-mediated cell lysis via suppressing the biological
      activity of C3. Therefore, C1INH, in addition to inhibition of the systemic
      complement activation, prevents myocardial cell injury via a direct inhibitory
      role in the local myocardial C3 activity.

PMID- 16996481
TI  - Respiratory chain dysfunction in skeletal muscle does not cause insulin
      resistance.
AB  - Insulin resistance in skeletal muscle is a characteristic feature of diabetes
      mellitus type 2 (DM2). Several lines of circumstantial evidence suggest that
      reduced mitochondrial oxidative phosphorylation capacity in skeletal muscle is a
      primary defect causing insulin resistance and subsequent development of DM2. We
      have now experimentally tested this hypothesis by characterizing glucose
      homeostasis in tissue-specific knockout mice with progressive respiratory chain
      dysfunction selectively in skeletal muscle. Surprisingly, these knockout mice are
      not diabetic and have an increased peripheral glucose disposal when subjected to
      a glucose tolerance test. Studies of isolated skeletal muscle from knockout
      animals show an increased basal glucose uptake and a normal increase of glucose
      uptake in response to insulin. In summary, our findings indicate that
      mitochondrial dysfunction in skeletal muscle is not a primary etiological event
      in DM2.

PMID- 16996482
TI  - Synergistic effects of the anti-cholinergic R,R-glycopyrrolate with anti
      inflammatory drugs.
AB  - Currently, much effort is geared towards developing therapies that impact on the
      inflammation in respiratory diseases such as asthma and COPD, assuming that this
      will improve disease pathology. R,R-Glycopyrrolate, a quaternary ammonium
      compound, is a muscarinic receptor antagonist with the potential to be used as a
      long-acting bronchodilator in patients with asthma and COPD. In this study we
      evaluated whether the combination of R,R-glycopyrrolate with known anti
      inflammatory drugs results in synergistic effects. Human primary monocytes were
      used as an in vitro model system. M3, M4, M1 and M2 receptors were expressed in
      these cells in descending order. The combinatory effects of the drugs on the
      release of TNF-alpha after lipopolysaccharide stimulation were analyzed. R,R
      Glycopyrrolate alone did not affect LPS induced TNF-alpha release. The PDE4
      inhibitor rolipram dose dependently inhibited the TNF-alpha release. Maximum
      inhibition was around 70%. The IC(35) for rolipram was 68.9+/-15.2 nM. The
      simultaneous administration of 10 microM R,R-glycopyrrolate reduced the IC(35) to
      1.70+/-1.18 nM. The anti-histamine azelastine inhibited TNF-alpha release dose
      dependently. The simultaneous administration of R,R-glycopyrrolate did not
      influence the action of azelastine. The corticosteroid budesonide inhibited the
      TNF-alpha release dose dependently with an IC(50) of 0.55+/-0.13 nM. The
      simultaneous administration of 10 microM R,R-glycopyrrolate reduced the IC(50) to
      0.13+/-0.03 nM. Finally, R,R-glycopyrrolate was most effective in the triple
      combination with budesonide and rolipram in the reduction of TNF-alpha release.
      In conclusion, R,R-glycopyrrolate acts synergistically with the PDE4 inhibitor
      rolipram and the steroid budesonide in inhibiting inflammatory mediators.

PMID- 16996483
TI  - Vascular depression: A distinct diagnostic subtype?
AB  - Vascular depression has been proposed as a unique and valid diagnostic subtype on
      the basis of studies of external (concurrent and predictive) validity. Validating
      a diagnostic entity on the basis of external validity is problematic, because it
      presupposes that the construct is well defined (i.e., the proposed features
      cluster together to define a distinct patient group). Because such evidence has
      not been obtained, we propose that the next critical step in evaluating this
      potential subtype is to establish internal (construct) validity and highlight
      taxometric analysis and latent class cluster analysis as illustrative
      multivariate statistical techniques that can be used in this effort. The
      psychometric approach advocated here (despite its inherent assumptions and
      limitations) might substantially improve on previous diagnostic efforts (e.g.,
      expert consensus), and vascular depression might serve as a prototype for future
      psychiatric classification.

PMID- 16996484
TI  - Haplotype analysis and a novel allele-sharing method refines a chromosome 4p
      locus linked to bipolar affective disorder.
AB  - BACKGROUND: Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common
      conditions. Their causes are unknown, but they include a substantial genetic
      component. Previously, we described significant linkage of BPAD to a chromosome
      4p locus within a large pedigree (F22). Others subsequently have found evidence
      for linkage of BPAD and SCZ to this region. METHODS: We constructed high
      resolution haplotypes for four linked families, calculated logarithm of the odds
      (LOD) scores, and developed a novel method to assess the extent of allele sharing
      within genes between the families. RESULTS: We describe an increase in the F22
      LOD score for this region. Definition and comparison of the linked haplotypes
      allowed us to prioritize two subregions of 3.8 and 4.4 Mb. Analysis of the extent
      of allele sharing within these subregions identified 200 kb that shows increased
      allele sharing between families. CONCLUSIONS: Linkage of BPAD to chromosome 4p
      has been strengthened. Haplotype analysis in the additional linked families
      refined the 20-Mb linkage region. Development of a novel allele-sharing method
      allowed us to bridge the gap between conventional linkage and association
      studies. Description of a 200-kb region of increased allele sharing prioritizes
      this region, which contains two functional candidate genes for BPAD, SLC2A9, and
      WDR1, for subsequent studies.

PMID- 16996485
TI  - Meta-analysis of aggression or hostility events in randomized, controlled
      clinical trials of atomoxetine for ADHD.
AB  - BACKGROUND: We systematically examined potential aggression/hostility-related
      events in a meta-analysis of acute clinical trials of atomoxetine for attention
      deficit/hyperactivity disorder (ADHD). METHODS: Pediatric patients from 14 trials
      of atomoxetine were subdivided into a placebo-controlled (atomoxetine n = 1308,
      placebo n = 806) or active comparator databases (atomoxetine n = 566,
      methylphenidate n = 472). A third database comprised adult patients from placebo
      controlled studies (atomoxetine n = 541, placebo n = 405). A computerized search
      of adverse events and comments identified patients with potential
      aggression/hostility events. Mantel-Haenszel incidence differences (MHID) were
      calculated. RESULTS: In the placebo-controlled database, we observed 21
      atomoxetine and 9 placebo patients with reported aggression/hostility events,
      MHID of .6% (95% confidence interval [CI]: -.4, 1.7). In the active comparator
      database, there were seven events in atomoxetine and four in methylphenidate
      patients, MHID = .2% (95% CI: -1.0,1.3). In the adult database, there were no
      events in 0 atomoxetine and one placebo patient, MHID = -.3% (95% CI: -.8, .2).
      CONCLUSIONS: Aggression/hostility-related events occurred in less than 2% of
      patients and were more frequent in pediatric patients treated with atomoxetine
      versus placebo (risk ratio of 1.33; not statistically significant). The risk of
      aggression/hostility events was similar in patients treated with atomoxetine or
      methylphenidate.

PMID- 16996486
TI  - Recent advances in the genetics of autism.
AB  - Autism is a strongly genetic disorder, with an estimated heritability of greater
      than 90%. Nonetheless, its specific genetic etiology remains largely unknown.
      Over the past several years, the convergence of rapidly advancing genomic
      technologies, the completion of the human genome project, and successful
      collaborative efforts to increase the number of deoxyribonucleic acid samples
      available for study have led to the first solid clues regarding the genetic
      origins of autism spectrum disorders. This article addresses the obstacles that
      have confronted gene discovery efforts and reviews recent linkage, cytogenetic,
      and candidate gene association studies relevant to autism spectrum disorders. In
      addition, promising avenues for future research and the potential contribution of
      emerging genomic technologies are considered.

PMID- 16996487
TI  - Decreased numbers of regulatory T cells suggest impaired immune tolerance in
      children with tourette syndrome: a preliminary study.
AB  - BACKGROUND: Post-streptococcal autoimmune inflammation of basal ganglia was
      suggested to be an etiological factor in some cases of Tourette syndrome (TS).
      Since regulatory T (T reg) cells play a major role in preventing autoimmunity, we
      hypothesized that a defect in T reg cells may be present in children with TS. We
      also postulated that group A beta hemolytic streptococcal infections could
      promote autoimmune responses by releasing exotoxins (streptococcal pyrogenic
      exotoxins [SPE]). METHODS: We analyzed peripheral blood of TS patients and
      healthy age-matched control subjects by fluorescence-activated cell sorting
      (FACS) on multiple occasions and determined the numbers of CD4(+)CD25(+)CD69(-) T
      reg cells. Further, we quantified the number of CD4(+) and CD8(+) lymphocytes
      with regard to Vbeta chains to which SPEs are known to bind. RESULTS: A
      significant decrease in T reg cells was observed in patients with moderate to
      severe TS symptoms compared with healthy age-matched control children. A decrease
      in T reg cell number was also noted during symptom exacerbations in five out of
      six patients. Further, we found a significant decrease in numbers of
      CD8(+)Vbeta18(+) T cells in moderate to severe TS patients. CONCLUSIONS: These
      data support our hypothesis that at least some TS patients may have a decreased
      capacity to inhibit autoreactive lymphocytes through a deficit in T reg cells.
      Interactions of host T cell immunity and microbial factors may also contribute to
      the pathogenesis of TS.

PMID- 16996488
TI  - Frontostriatal dysfunction during response inhibition in Williams syndrome.
AB  - BACKGROUND: Williams syndrome (WS) has provided researchers with an exciting
      opportunity to understand the complex interplay among genes, neurobiological and
      cognitive functions. However, despite a well-characterized cognitive and
      behavioral phenotype, little attention has been paid to the marked deficits in
      social and behavioral inhibition. Here we explore the neural systems that mediate
      response inhibition in WS. METHODS: We used functional MRI (fMRI) to obtain blood
      oxygenation level dependence (BOLD) signal maps during the performance of a
      Go/NoGo response inhibition task from 11 clinically and genetically diagnosed WS
      patients and 11 age- and gender-matched typically developing (TD) control
      subjects. Correlations between behavioral, neuropsychological measures, and BOLD
      signal were also conducted. RESULTS: Although TD control subjects showed
      significantly faster response times, no group differences in behavioral accuracy
      were observed. Compared with control subjects, WS participants demonstrated
      significantly reduced activity in the striatum, dorsolateral prefrontal, and
      dorsal anterior cingulate cortices. These findings support the hypothesis that
      persons with WS fail to activate critical cortical and subcortical structures
      involved in behavioral inhibition. CONCLUSIONS: Our results provide important
      evidence for reduced engagement of the frontostriatal circuits in WS and provide
      putative biological markers for the deficits in response inhibition and the
      unusual social phenotype.

PMID- 16996489
TI  - Implantation of a scaffold following bulbectomy induces laminar organization of
      regenerating olfactory axons.
AB  - Primary olfactory axons expressing different odorant receptors are interspersed
      within the olfactory nerve. However, upon reaching the outer nerve fiber layer of
      the olfactory bulb they defasciculate, sort out, and refasciculate prior to
      targeting glomeruli in fixed topographic positions. While odorant receptors are
      crucial for the final targeting of axons to glomeruli, it is unclear what directs
      the formation of the nerve fiber and glomerular layers of the olfactory bulb.
      While the olfactory bulb itself may provide instructive cues for the development
      of these layers, it is also possible that the incoming axons may simply require
      the presence of a physical scaffold to establish the outer laminar
      cytoarchitecture. In order to begin to understand the underlying role of the
      olfactory bulb in development of the outer layers of the olfactory bulb, we
      physically ablated the olfactory bulbs in OMP-IRES-LacZ and P2-IRES-tau-LacZ
      neonatal mice and replaced them with artificial biological scaffolds molded into
      the shape of an olfactory bulb. Regenerating axons projected around the edge of
      the cranial cavity at the periphery of the artificial scaffold and were able to
      form an olfactory nerve fiber layer and, to some extent, a glomerular layer. Our
      results reveal that olfactory axons are able to form rudimentary
      cytoarchitectonic layers if they are provided with an appropriately shaped
      biological scaffold. Thus, the olfactory bulb does not appear to provide any
      tropic substance that either attracts regenerating olfactory axons into the
      cranial cavity or induces these axons to form a plexus around its outer surface.

PMID- 16996490
TI  - Simulation of cerebral hemodynamics for preoperative risk assessment.
AB  - BACKGROUND: An important part of the medical treatment of many cerebrovascular
      diseases is the occlusion of brain supplying arteries. Until now, the risk of
      this intervention can only be estimated by invasive diagnostics including the
      risk of cerebrovascular accidents. METHODS AND RESULTS: As a supporting tool, a
      computer model of the circle of Willis was designed. The model is based upon
      linear differential equations describing electrotechnical circuits extended non
      linearly. By these means, time continuous simulations of different states and the
      online observation of all calculated state variables such as blood pressure and
      blood flow in every modeled vessel became feasible. For individual simulations,
      model parameters were determined by MR-angiography and boundary values by
      simultaneous Duplex-measurements in both carotid and vertebral arteries. State
      variables generated by the model behaved physiologically and the reaction of
      individual cerebrovascular systems in critical situations could be investigated
      by special scenarios. Inaccuracies concerning the determination of model
      parameters and boundary values of the used differential equations are likely to
      be resolved in the near future through a more careful and technically improved
      determination of these values. CONCLUSIONS: Computer models of subjects were
      created taking in account the individual anatomical and non-linear physical
      properties of real vascular systems supplying the brain. Thereby information
      could be obtained concerning the hemodynamic effects of an iatrogenic vascular
      occlusion.

PMID- 16996491
TI  - Unconscious modulation of the conscious experience of voluntary control.
AB  - How does the brain generate our experience of being in control over our actions
      and their effects? Here, we argue that the perception of events as self-caused
      emerges from a comparison between anticipated and actual action-effects: if the
      representation of an event that follows an action is activated before the action,
      the event is experienced as caused by one's own action, whereas in the case of a
      mismatch it will be attributed to an external cause rather than to the self. In a
      subliminal priming paradigm we show that participants overestimated how much
      control they had over objectively uncontrollable stimuli, which appeared after
      free- or forced-choice actions, when a masked prime activated a representation of
      the stimuli immediately before each action. This prime-induced control-illusion
      was independent from whether primes were consciously perceived. Results indicate
      that the conscious experience of control is modulated by unconscious
      anticipations of action-effects.

PMID- 16996492
TI  - A novel method for analysis of single ion channel signal based on wavelet
      transform.
AB  - A single ion channel signal was analysed by the power distribution fraction
      constructed by a discrete wavelet transform. Average opening time and energy
      distribution of the signal can be obtained directly by this method. The method
      can also be used when the signal is corrupted by noise. By contrast, the
      conventional frequency domain analysis method--power spectral density--is less
      effective. Power distribution fraction will therefore give more useful
      information in analysis of experimental ion channel signals, principally by
      giving values of the mean channel opening time. The method may be applied to
      distinguish different ion channels more efficiently and to find their reactions
      to drugs.

PMID- 16996494
TI  - Cooperative Mesp activity is required for normal somitogenesis along the anterior
      posterior axis.
AB  - Mesp2 is a bHLH-type transcription factor that plays a key role during
      somitogenesis. Mesp2 is transiently expressed and is quickly degraded once
      translated. In our current study, we find that Mesp2 contains a degradation
      domain, which acts as a target of proteasome-mediated proteolysis and appears to
      play this role in vivo. We have also defined the nuclear localization signals
      (NLS) and constructed a minimum Mesp2 protein (P2-HD) composed of the NLS, bHLH
      and the degradation domains. The ability of the P2-HD as a transcription factor
      in vivo was examined. Some of the defects that had been previously observed in
      the Mesp2-null mice were rescued in the knock-in mice but only in the posterior
      half of the body, indicating differential effects of P2-HD along the anterior
      posterior (AP) axis. In addition, quantitative analysis of the expression along
      the AP axis revealed that the relative levels of Mesp2 increased, whereas Mesp1
      is down-regulated in the later stages of development by the activities of Mesp2
      in the wild-type embryo. Moreover, we have found that somitogenesis in the early
      stages is more susceptible to changes in the Mesp gene dosage, indicating that a
      threshold level of Mesp activity must be required for the progression of normal
      somitogenesis.

PMID- 16996493
TI  - Intermolecular interactions of homologs of germ plasm components in mammalian
      germ cells.
AB  - In some species such as flies, worms, frogs and fish, the key to forming and
      maintaining early germ cell populations is the assembly of germ plasm,
      microscopically distinct egg cytoplasm that is rich in RNAs, RNA-binding proteins
      and ribosomes. Cells which inherit germ plasm are destined for the germ cell
      lineage. In contrast, in mammals, germ cells are formed and maintained later in
      development as a result of inductive signaling from one embryonic cell type to
      another. Research advances, using complementary approaches, including
      identification of key signaling factors that act during the initial stages of
      germ cell development, differentiation of germ cells in vitro from mouse and
      human embryonic stem cells and the demonstration that homologs of germ plasm
      components are conserved in mammals, have shed light on key elements in the early
      development of mammalian germ cells. Here, we use FRET (Fluorescence Resonance
      Energy Transfer) to demonstrate that living mammalian germ cells possess specific
      RNA/protein complexes that contain germ plasm homologs, beginning in the earliest
      stages of development examined. Moreover, we demonstrate that, although both
      human and mouse germ cells and embryonic stem cells express the same proteins,
      germ cell-specific protein/protein interactions distinguish germ cells from
      precursor embryonic stem cells in vitro; interactions also determine sub-cellular
      localization of complex components. Finally, we suggest that assembly of similar
      protein complexes may be central to differentiation of diverse cell lineages and
      provide useful diagnostic tools for isolation of specific cell types from the
      assorted types differentiated from embryonic stem cells.

PMID- 16996495
TI  - Verapamil-sensitive Ca2+ channel regulation of Th1-type proliferation of splenic
      lymphocytes induced by Walker 256 tumor development in rats.
AB  - Recently, we demonstrated that verapamil, an L-type Ca2+ channel blocker,
      inhibits the activation of splenic lymphocytes during Walker 256 ascitic tumor
      development in adult rats. In the present study we have analyzed the changes in
      spleen size, splenic lymphocyte proliferation, white pulp organization and
      relative size as well as food intake, and levels of blood haemoglobin in Walker
      256 tumor bearing rats. These rats displayed a spleen enlargement associated with
      a significant increase in white pulp area and TCD8+ lymphocyte proliferation.
      Levels of interferon-gamma, but not of interleukin-10, were elevated in tumor
      bearing rats, indicating a Th1-type immune response. These manifestations were
      accompanied by reduced food intake and anaemia. Treatment of tumor bearing rats
      with verapamil avoided spleen enlargement and increased expression of cytokines,
      as well as the splenic TCD8+ lymphocyte proliferation. In addition, verapamil
      treatment promoted an exacerbation of the anorexia and anaemia caused by Walker
      tumor development. No such effect was observed in control rats treated with
      verapamil. Taken together, these findings suggest that verapamil inhibits the
      immune response to cancer, resulting in an increase of the systemic effects
      induced by Walker 256 tumor.

PMID- 16996496
TI  - High permeability of the anionic form restricts accumulation of indomethacin by
      cultured gastric surface epithelial cells exposed to low apical pH.
AB  - The 'ion-trapping' hypothesis suggests that the intracellular concentration of
      acidic non-steroidal anti-inflammatory drugs in gastric epithelial cells could be
      much higher than in the gastric lumen, and that such accumulation could
      contribute to their gastrotoxicity. Our aim was to examine the effect of the pH
      of the apical medium on the apical to basal transfer of the acidic drug
      indomethacin (pKa 4.5) across a gastric mucous epithelial cell monolayer, and to
      determine whether indomethacin accumulated in cells exposed to a low apical pH.
      Guinea-pig gastric mucous epithelial cells were grown on porous membrane culture
      inserts (Transwells) for 72 h. Transfer and accumulation of [14C] indomethacin
      were assessed by scintillation counting. Transfer of [3H]mannitol and measurement
      of trans-epithelial electrical resistance were used to assess integrity of the
      monolayer. Distribution of [14C] urea was used to estimate the intracellular
      volume of the monolayer. The monolayer was not disrupted by exposure of the
      apical face to media of pH>or=3, or by indomethacin. Transfer of indomethacin (12
      microM) to the basal medium increased with decreasing apical medium pH. The
      apparent permeability of the undissociated acid was estimated to be five times
      that of the anion. The intracellular concentration of indomethacin was
      respectively 5.3, 4.1 and 4.3 times that in the apical medium at pH 5.5, 4.5 and
      3.0. In conclusion, this study represents the first direct demonstration that
      indomethacin accumulates in gastric epithelial cells exposed to low apical pH.
      However, accumulation of indomethacin was moderate and the predictions of the ion
      trapping hypothesis were not met, probably due to the substantial permeability of
      anionic indomethacin across membranes.

PMID- 16996497
TI  - Neuroprotective effects of galanthamine and tacrine against glutamate
      neurotoxicity.
AB  - We examined the mechanisms of the neuroprotective effects of two central-type
      acetylcholinesterase inhibitors, galanthamine and tacrine, on nitric oxide
      mediated glutamate neurotoxicity using primary cultures from the cerebral cortex
      of fetal rats. Galanthamine and tacrine showed prominent protective effects
      against glutamate neurotoxicity. Mecamylamine, a nicotinic acetylcholine receptor
      antagonist, but not scopolamine, a muscarinic acetylcholine receptor antagonist,
      inhibited the protective effects of these inhibitors on glutamate neurotoxicity.
      Furthermore, dihydro-beta-erythroidine, an alpha4-nicotinic receptor antagonist,
      and methyllycaconitine, an alpha7-nicotinic receptor antagonist, inhibited the
      neuroprotective effects of galanthamine but not tacrine. Next, we investigated
      the site of action where galanthamine and tacrine prevent glutamate
      neurotoxicity. Both these acetylcholinesterase inhibitors prevented glutamate-
      and ionomycin-induced neurotoxicity, but only tacrine prevented S-nitrosocysteine
      induced neurotoxicity. These results suggest that galanthamine and tacrine
      protect cortical neurons from glutamate neurotoxicity via different mechanisms.

PMID- 16996498
TI  - Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases.
AB  - TRAIL has been suggested to induce the cell death in various tumor cells but not
      in normal cells; however, several studies have provided the evidence that TRAIL
      can induce the cell death in some normal cells including human normal
      hepatocytes, suggesting that TRAIL may show hepatic toxicity in human. In this
      study, we designed a pro-form of TRAIL (sTRAIL:IL-18) in that soluble TRAIL
      (sTRAIL) is fused to IL-18, and a matrix metalloproteinases (MMPs) cleavage site
      is introduced at the connecting site. We showed that sTRAIL:IL-18 has
      significantly diminished the killing activity in HeLa cells but regains the
      activity by releasing the free sTRAIL through MMP-2-mediated cleavage. In
      addition, the killing activity of sTRAIL:IL-18 was significantly increased in
      HeLa cells when active MMP-2 was produced by TNF-alpha. Taken together, the data
      suggested that the sTRAIL:IL-18 can be reactivated at the specialized areas where
      MMPs are pathologically produced.

PMID- 16996499
TI  - Sarin produces delayed cardiac and central autonomic changes.
AB  - The aim was to evaluate the acute and delayed effects of low dose sarin exposure
      on cardiac autonomic and brainstem catecholaminergic function in mice. The
      rationale was to expand our knowledge of the cardiovascular effects of this
      neurotoxic, acetylcholinesterase (AChE) inhibitor. C57BL/6 male mice with
      telemetric arterial catheters were injected with saline or sarin (8 microg/kg,
      0.05x LD(50); sc, two injections) with blood pressure (BP) measurements made at 1
      and 10 weeks after sarin exposure. BP and pulse interval variability (PI) and low
      and high frequency spectral oscillations were measured using autoregressive
      spectral analysis. In situ hybridization (ISH) was used to quantify tyrosine
      hydroxylase (TH) mRNA expression in brainstem cardiovascular centers. Sarin had
      no effect on blood AChE activity, heart rate (HR) or BP. There was a biphasic
      response in PI variance, an early increase (+140%) and a delayed decrease (-62%)
      at more than 2 months after sarin exposure. There were no changes in BP variance.
      Assuming that increased PI variance is a positive outcome, the short-term
      response to sarin should be protective. This is opposite for the delayed decrease
      in PI variance which is associated with adverse cardiovascular effects. There was
      an increase in TH mRNA in both locus coeruleus (0.18+/-0.05 vs. 1.4+/-0.2
      microCi/g; control vs. sarin) and dorsal vagal complex (0.09+/-0.06 vs. 1.17+/
      0.03 microCi/g; control vs. sarin). Results show that a dose of sarin which had
      no peripheral cholinergic effects caused changes in autonomic modulation, a short
      term enhancement followed by a delayed impairment in heart rate variability.
      Sarin-induced cardiac effects suggest a controversial aspect to the use of
      pharmacological agents which target AChE for management of cardiovascular risk.

PMID- 16996500
TI  - Identification of a biphasic signaling pathway involved in ischemic resistance of
      the hippocampal dentate gyrus.
AB  - Dentate gyrus is usually assumed to be resistant to ischemia. However, the
      mechanisms underlying this functional plasticity are not fully understood.
      Herein, we aimed at identifying a neuroprotective mechanism in the dentate gyrus
      of the adult rat after global ischemia. Cyclic AMP response element (CRE)-binding
      protein (CREB), brain-derived neurotrophic factor (BDNF) and calcium/calmodulin
      dependent protein kinase IV (CaMKIV) are known to be mediators of neuronal
      survival and plasticity. Involvement of CaMKIV, BDNF and CREB in ischemic
      resistance was therefore examined using intracerebroventricular injections of
      pharmacological agents such as inhibitors, antibodies and consensus
      oligonucleotides followed by immunohistochemical and Western blot analysis. We
      provide evidence that ischemia triggers activation of a biphasic pathway during
      the resistance period of dentate neurons: (1) CaMKIV mediates the early
      phosphorylation of CREB which drives a prominent synthesis of BDNF; (2) this BDNF
      synthesis, in turn, induces a second peak of CREB phosphorylation which is
      required for the maintenance of BDNF synthesis. In addition, we show that: (1)
      impairment of these transduction signals by the pharmacological agents causes
      tissular damages and apoptotic deaths in the post-ischemic dentate gyrus; (2)
      some similar disturbances also occur beyond the resistance period in the dentate
      gyrus of untreated ischemic rats; (3) these disturbing effects are mainly
      observed in the suprapyramidal dentate subfield. Collectively, the present
      results suggest that activation of the CaMKIV/CREB/BDNF pathway plays principally
      an early protective role in the suprapyramidal subfield of the dentate gyrus.

PMID- 16996501
TI  - A new paradigm for membrane-organizing and -shaping scaffolds.
AB  - The clathrin, COPI and COPII scaffolds are paradigm vesicle coats in membrane
      trafficking. Recent advances in our understanding of the caveolar coat have
      generated a new paradigm. It represents those membrane coats, where a
      considerable part of the protein component is lipid modified, and integrated into
      the cytosolic leaflet of the vesicle membrane by a hairpin-like hydrophobic
      structure. Such coat proteins are permanently associated with membranes, and form
      oligomers early after synthesis. These oligomers assemble into a coat that has
      high affinity for particular lipids, creating lipid microdomains within the
      membrane. The combined protein-lipid structure should be considered as the
      scaffold that entraps ligands, either through affinity with the protein or with
      the lipid component, and that has the ability to shape membranes. Besides
      scaffolds assembled by caveolins, scaffolds assembled by reticulons and PHB
      domain-containing proteins such as the reggie/flotillin proteins fit this
      paradigm.

PMID- 16996502
TI  - Identification of cDNAs encoding pterocarpan reductase involved in isoflavan
      phytoalexin biosynthesis in Lotus japonicus by EST mining.
AB  - Isoflavans and pterocarpans are the major biosynthetically connected phytoalexins
      in legumes. A search of the expressed sequence tag library of a model legume
      Lotus japonicus, which produces an (-)-isoflavan, for homologs of phenylcoumaran
      benzylic ether reductase catalyzing the reductive cleavage of dihydrofurans,
      yielded seven full-length cDNAs, and the encoded proteins were analyzed in vitro.
      Four of them cleaved the dihydrofuran of a pterocarpan medicarpin to yield an
      isoflavan (-)-vestitol and were designated pterocarpan reductase (PTR). Two PTRs
      displayed enantiospecificity to (-)-medicarpin, representing genuine L. japonicus
      PTRs, while the other two lacked enantiospecificity and were presumed to be
      evolutionarily primitive types.

PMID- 16996503
TI  - Myc stabilization in response to estrogen and phospholipase D in MCF-7 breast
      cancer cells.
AB  - Estrogen, which has been strongly implicated in breast cancer, suppresses
      apoptosis in estrogen receptor (ER) positive MCF-7 breast cancer cells.
      Phospholipase D (PLD), which is commonly elevated in ER negative breast cancer
      cells, also suppresses apoptosis. Survival signals generated by both estrogen and
      PLD are dependent upon elevated Myc expression. We report here that estrogen- and
      PLD-induced increases in Myc expression are due to reduced turnover of Myc
      protein. Estrogen and PLD suppressed phosphorylation of Myc at Thr58--a site that
      targets Myc for degradation by the proteasome. The data provide a mechanism for
      elevated Myc expression in hormone-dependent and hormone-independent breast
      cancer.

PMID- 16996504
TI  - Occurrence of A-kinase anchor protein and associated cAMP-dependent protein
      kinase in the inner compartment of mammalian mitochondria.
AB  - Evidence showing the existence in the inner compartment of rat-heart mitochondria
      of AKAP121 and associated PKA is presented. Immunoblotting analysis and trypsin
      digestion pattern show that 90% or more of mitochondrial C-PKA, R-PKA and AKAP121
      is localized in the inner mitochondrial compartment, when prepared both from
      isolated mitochondria or cardiomyocyte cultures. This localization is verified by
      measurement of the specific catalytic activity of PKA, radiolabelling of R-PKA by
      (32)P-phosphorylated C-PKA and of AKAP by (32)P-phosphorylated R-PKA and electron
      microscopy of mitochondria exposed to gold-conjugated AKAP121 antibody.

PMID- 16996505
TI  - Muscle atrophy in transgenic mice expressing a human TSC1 transgene.
AB  - Muscle mass is regulated by a wide range of hormonal and nutritional signals,
      such as insulin and IGF. Tuberous sclerosis complex (TSC) is an inherited
      hamartoma disease with tumor growth in numerous organs. TSC is caused by mutation
      in either TSC1 or TSC2 tumor suppressor genes that negatively regulate insulin
      induced S6K activation and cell growth. Here we report that expression of human
      TSC1 (hTSC1) in mouse skeletal muscle leads to reduction of muscle mass.
      Expression of hTSC1 stabilizes endogenous TSC2 and leads to inhibition of the
      mTOR signaling. The hTSC1-mTSC2 hetero-complex and its downstream components
      remain sensitive to insulin stimulation and nutrition signals. This study
      suggests that an increase in the steady state level of resident TSC1-TSC2 complex
      is sufficient to reduce muscle mass and cause atrophy.

PMID- 16996506
TI  - Bimodal actions of reactive oxygen species in the differentiation and bone
      resorbing functions of osteoclasts.
AB  - In order to demonstrate that cellular redox status undergoes decreased reduction
      during osteoclast differentiation and further decreased reduction during
      osteoclastic bone resorption, we analyzed gamma-glutamylcysteinyl synthetase
      activity, a glutathione synthesis rate-limiting enzyme, and total glutathione and
      thiol groups. Moderate and severe redox shifts towards a more oxidizing
      environment induced gradual increases and decreases in osteoclastogenesis.
      Moreover, while severe glutathione depletion inhibited bone resorption, moderate
      glutathione repletion enhanced bone resorption. In summary, our observations
      suggest that there is a threshold for redox status, representing biphasic
      patterns in osteoclast differentiation and function.

PMID- 16996507
TI  - Bone mineral density loss and recovery during 48 months in first-time users of
      depot medroxyprogesterone acetate.
AB  - OBJECTIVE: To compare changes in bone mineral density (BMD) during 48 months
      between first-time depot medroxyprogesterone acetate (MPA) users, during use and
      after discontinuation, to controls. DESIGN: Longitudinal study. SETTING: Academic
      community. PATIENT(S): Women 18-35 years, newly initiating depot MPA (n = 178)
      and controls (n = 145) not using hormonal contraception. MAIN OUTCOME MEASURE(S):
      The BMD of the hip and spine, measured at 3-month intervals, by dual energy
      roentgen absorptiometry. RESULTS: Hip and spine BMD declined during 48 months of
      depot MPA use by 7.7% +/- 0.11% (mean +/- SE) and 6.4% +/- 0.36%, respectively.
      The BMD of controls declined <or=1.6% +/- 0.30%. Hip and spine BMD loss slowed to
      <0.6% after 48 months of depot MPA use. After discontinuation, BMD increased from
      0.3% to 2.0% per year depending on length of depot MPA use and bone site. The
      longest depot MPA users remained 4.7% and 2.9% lower than hip and spine baseline
      values, respectively, 18 months after discontinuation. CONCLUSION(S): Depot MPA
      related BMD loss is substantial but occurs mostly during the first 2 years of
      DMPA use. Therefore, longer use may not substantially increase the risk of
      osteoporosis. The prolonged recovery time suggests the need to consider timing of
      use in relation to menopause or other factors that may impede bone remodeling.

PMID- 16996508
TI  - In vitro maturation of human oocytes for assisted reproduction.
AB  - OBJECTIVE: To describe and evaluate the current practice of in vitro maturation
      of oocytes for assisted reproduction. DESIGN: Review of the available and
      relevant literature regarding in vitro maturation of oocytes. CONCLUSION(S): In
      vitro maturation of human oocytes retrieved from antral ovarian follicles is an
      emerging procedure quickly being incorporated into the realm of assisted
      reproductive technologies. This new technology has several potential advantages
      over traditional controlled ovarian hyperstimulation for IVF, such as reduction
      of costs by minimizing gonadotropin and GnRH analogue use, elimination of ovarian
      hyperstimulation syndrome, and simplicity of protocol. In vitro maturation of
      oocytes for assisted reproduction in human beings still is undergoing refinement
      but currently is providing efficacy and safety outcome comparable to that of
      traditional IVF in recent selected studies. Implementing in vitro maturation into
      an established IVF practice is feasible and requires only a few simple
      adjustments. Crucial to the advancement and optimization of the technology is a
      better understanding of how to maximize immature oocyte developmental competence
      and endometrial receptivity.

PMID- 16996509
TI  - The effectiveness of modified sperm washes in severely oligoasthenozoospermic men
      infected with human immunodeficiency and hepatitis C viruses.
AB  - Men who are seropositive for human immunodeficiency virus (HIV) or hepatitis C
      virus now can father children safely, thanks to sperm washing and nested
      polymerase chain-reaction techniques, followed by intracytoplasmic sperm
      injection. However, in a small percentage of such patients, it is impossible to
      recover spermatozoa after said procedures because of their highly impaired
      spermatogenesis. We have established that less rigorous methods, such as repeated
      centrifugation, yield nested polymerase chain-reaction HIV- and hepatitis C virus
      negative specimens, even in sperm samples from men with severe
      oligoasthenozoospermia.

PMID- 16996510
TI  - Successful strategy for the hysteroscopic myomectomy of a submucous myoma arising
      from the uterine fundus.
AB  - OBJECTIVE: To introduce a technique for hysteroscopic resection of submucous
      myoma arising from the uterine fundus. DESIGN: Case report. SETTING: University
      hospital. PATIENT(S): A 43-year-old nulliparous Japanese woman. INTERVENTION(S):
      An original combination technique of hysteroresectoscopy using circumferential
      myoma scraping, central vaporization, and intraoperative injection of
      prostaglandin F2alpha. MAIN OUTCOME MEASURE(S): Evaluation of clinical symptoms
      and imaging diagnosis. RESULT(S): Resection of a 40-mm fundal myoma was performed
      hysteroscopically, and the menorrhagia of the patient was remedied by the
      operation. CONCLUSION(S): Although large sessile fundal myomas are difficult to
      resect by hysteroscopic myomectomy, our original strategy may allow safe and
      certain surgery in such cases.

PMID- 16996511
TI  - Iatrogenic peritoneal adenomyoma after laparoscopic subtotal hysterectomy and
      uterine morcellation.
AB  - Five years after laparoscopic subtotal hysterectomy and morcellation, pelvic
      magnetic resonance imaging demonstrated the presence of an irregular and
      heterogeneous pelvic mass measuring 40 x 40 x 30 mm. Histologic examination
      confirmed smooth muscle hyperplasia infiltrated by numerous endometrial glands
      (adenomyosis).

PMID- 16996512
TI  - The functionality of mitochondria differentiates human spermatozoa with high and
      low fertilizing capability.
AB  - By using flow-cytometric sorting, we compared some of the major factors related
      to fertility in sperm subpopulations with high and low mitochondrial membrane
      potential (DeltaPsi(m)). Results demonstrate that DeltaPsi(m)(high) spermatozoa
      represents a subpopulation of sperm with high fertility performance because they
      have normal morphology, high motility values, and calcium ionophore-induced
      acrosome reaction, suggesting the importance of mitochondrial functionality for
      fertilizing capacity of human spermatozoa.

PMID- 16996513
TI  - Role of poly(ADP-ribosyl)ation during human spermatogenesis.
AB  - OBJECTIVE: Genomic stability of cells is known to be linked to their poly(ADP
      ribosyl)ation capacity. We aimed to demonstrate, for the first time, the patterns
      of poly(ADP-ribosyl)ation during human spermatogenesis. DESIGN: Retrospective
      case-control study. SETTING: Teaching hospital. PATIENT(S): Azoospermic men who
      underwent testicular biopsy for sperm recovery. INTERVENTION(S): Testicular
      biopsy evaluation by immunohistochemistry for the expression of poly(ADP-ribose)
      polymerase-1 (PARP-1) enzyme and of poly(ADP-ribose) (PAR) (an indicator for PARP
      activity.) MAIN OUTCOME MEASURE(S): The subcellular localization of both markers
      in testes with full spermatogenesis (obstructive azoospermia), spermatocyte
      maturation arrest, or Sertoli cell-only syndrome. RESULT(S): Expression of both
      markers was localized in germ cell nuclei in full spermatogenesis: PAR
      expression, indicating PARP activity, was exhibited in round and elongating
      spermatids and in a subpopulation of primary spermatocytes. Strong
      immunoreactivity for PAR was identified in all of the spermatocytes in maturation
      arrest at the spermatocyte level. Sertoli cells lacked immunoreactivity for both
      markers, whereas other somatic testicular cells were rarely immunostained.
      CONCLUSION(S): The detection of PAR expression in germ-line cells and its
      subcellular localization in meiotic and postmeiotic prophases demonstrates
      chromatin modifications occurring during spermatogenesis and establishes a key
      role for poly(ADP-ribosyl)ation in germ cell differentiation, presumably to
      safeguard DNA integrity.

PMID- 16996514
TI  - Health outcomes of adults 3 months after injury.
AB  - BACKGROUND: Injury is a leading cause of preventable mortality and morbidity in
      Australia and the world. Despite this there is little research examining the
      health related quality of life of adults following general trauma. METHODS: A
      prospective cohort design was used to study adults who presented to hospital
      following injury. Data regarding injury and demographic details was collected
      through the routine operation of the Queensland Trauma Registry (QTR). In
      addition, the short form 36 (SF-36) was mailed to patients approximately 3 months
      following injury. RESULTS: Participants included 339 injured patients who were
      hospitalised for >or=24h in March-June 2003. A secondary group of 145 patients
      completed the SF-36, but did not have QTR data collected due to hospitalisation
      being <24h. Both groups of participants reported significantly lower scores on
      all subscales of the SF-36 when compared to Australian norms. CONCLUSIONS: Health
      related quality of life of injured survivors is markedly reduced 3 months after
      injury. Ongoing treatment and support is necessary to improve these health
      outcomes.

PMID- 16996515
TI  - Immediate application of improvised pelvic binder as first step in extended
      resuscitation from life-threatening hypovolaemic shock in conscious patients with
      unstable pelvic injuries.

PMID- 16996516
TI  - The effectiveness of a nurse-initiated intervention to reduce catheter-associated
      bloodstream infections in an urban acute hospital: an intervention study with
      before and after comparison.
AB  - BACKGROUND: Catheter care is considered to be important for prevention of
      catheter-associated bloodstream infections (CABSIs) although epidemiological
      evidence is sparse. OBJECTIVES: To identify problems associated with catheter
      care and evaluate the effectiveness of nurse-initiated interventions to reduce
      CABSIs. DESIGN: An intervention study with before and after comparison. SETTINGS:
      CABSI surveillance was conducted in a 560-bed acute hospital located in a major
      urban area in Japan. PARTICIPANTS: Patients were enrolled in this study from
      April 2000 to December 2002 based on the following criteria: (1) adult
      inpatients; and (2) those in whom central venous lines or Swan-Ganz catheters
      were inserted for 2 days or longer. METHODS: In the first year, risk factors for
      CABSI and problems associated with catheter care were identified by inspection of
      the infection control nurse (ICN) or four trained link nurses, and the laboratory
      results. In the subsequent 2 years, the following interventions based on the
      surveillance results were implemented: (1) enhanced skin preparation by scrubbing
      with regular bathing soap and tap water; (2) a new method for stabilisation of
      the catheter inserted into the internal jugular vein, where additional dressing
      was placed over the sterilised dressing; (3) educating the staff on maximal
      sterile precautions by teaching staff members at their section meetings and
      displaying posters; (4) use of a check list and observation of catheter insertion
      by link nurses to monitor compliance; and (5) selection of a disinfectant that
      requires shorter contact time and has longer residual effect. RESULTS: After
      these interventions were implemented, the overall bloodstream infection (BSI)
      rate declined from 4.0/1000 device-days to 1.1/1000 device-days (p<0.005).
      CONCLUSIONS: We identified four problems-those related to skin preparation,
      dressing, sterile precautions and disinfectant. We implemented a series of
      interventions to reduce CABSIs; the overall CABSI rate decreased significantly.

PMID- 16996517
TI  - Assessing the impact of training on mental health nurses' therapeutic attitudes
      and knowledge about co-morbidity: a randomised controlled trial.
AB  - BACKGROUND: Substance misuse can trigger or be causally associated with mental
      health problems. Therapeutic attitude is important in predicting effective
      engagement with people with alcohol and drug problems but health professionals'
      attitudes towards this client group are often negative. Education regarding
      substance misuse has often been neglected and nurses may lack knowledge to
      provide appropriate care. OBJECTIVES: To test the impact of training for staff
      who work with people who have co-existing mental health and substance use
      problems. DESIGN: A randomised controlled trial. SETTING: An NHS Primary Care
      Division in the West of Scotland. PARTICIPANTS: Forty-nine mental health nurses.
      METHODS: Intervention. A four-day training programme. MEASUREMENTS: (a)
      therapeutic attitudes measured by the co-morbidity problems perceptions
      questionnaire; (b) knowledge of alcohol, drugs and co-morbidity measured by a
      structured questionnaire. RESULTS: Significant effects for group (F=30.42,
      p<0.001) were found in therapeutic attitude scores and also over time (F=10.66,
      p<0.001). A significant interaction was also found (p<0.001). Post-hoc testing
      revealed that the mean pre-training attitude score was significantly different
      from post-training (p=0.001; 95% CI 5.53, 25.38) and from six-months follow-up
      (p<0.001; 95% CI 11.26, 32.49) but that post-training and follow-up mean scores
      were not significantly different (p=0.358; 95% CI -4.71, 17.55). For knowledge, a
      significant group effect was found (F=10.32, p=0.002), and also a significant
      time effect (F=3.35, p=0.039) but no significant interaction effect was present
      (p=0.169). The post-hoc testing revealed that only a pre-training to six-month
      follow-up time effect was statistically significant (p=0.005; 95% CI 1.37, 9.29).
      CONCLUSIONS: The training programme was effective in improving the therapeutic
      attitudes of participants to working with clients who have co-existing mental
      health and substance use problems, both immediately after the training was
      delivered, and at six-months follow-up. It was also effective in improving
      participants' overall knowledge of alcohol, drugs and co-morbidity.

PMID- 16996518
TI  - LipoCardium: endothelium-directed cyclopentenone prostaglandin-based liposome
      formulation that completely reverses atherosclerotic lesions.
AB  - Atherosclerosis is a multifactorial inflammatory disease of blood vessels which
      decimates one in every three people in industrialized world. Despite the
      important newest clinical approaches, currently available strategies (e.g.
      nutritional, pharmacological and surgical) may only restrain the worsening of
      vascular disease. Since antiproliferative cyclopentenone prostaglandins (CP-PGs)
      are powerful anti-inflammatory agents, we developed a negatively charged liposome
      based pharmaceutical formulation (LipoCardium) that specifically direct CP-PGs
      towards the injured arterial wall cells of atherosclerotic mice. In the blood
      stream, LipoCardium delivers its CP-PG contents only into activated arterial wall
      lining cells due to the presence of antibodies raised against vascular cell
      adhesion molecule-1 (VCAM-1), which is strongly expressed upon inflammation by
      endothelial cells and macrophage-foam cells as well. After 4 months in a high
      lipid diet, all low-density lipoprotein receptor-deficient adult control mice
      died from myocardium infarction or stroke in less than 2 weeks, whereas
      LipoCardium-treated (2 weeks) animals (still under high-lipid diet) completely
      recovered from vascular injuries. In vitro studies using macrophage-foam cells
      suggested a tetravalent pattern for LipoCardium action: anti-inflammatory,
      antiproliferative (and pro-apoptotic only to foam cells), antilipogenic and
      cytoprotector (via heat-shock protein induction). These astonishing cellular
      effects were accompanied by a marked reduction in arterial wall thickness,
      neointimal hyperplasia and lipid accumulation, while guaranteed lifespan to be
      extended to the elderly age. Our findings suggest that LipoCardium may be safely
      tested in humans in a near future and may have conceptual implications in
      atherosclerosis therapy.

PMID- 16996519
TI  - Cholesterol metabolism and non-cholesterol sterol distribution in lipoproteins of
      type 1 diabetes: the effect of improved glycemic control.
AB  - In type 1 diabetes, the ratios to cholesterol of serum absorption markers, e.g.,
      cholestanol, are elevated and those of synthesis markers, e.g., lathosterol, are
      reduced suggesting perturbed cholesterol metabolism. We studied 17 subjects with
      type 1 diabetes in poor glycemic control at baseline to assess whether
      improvement of glycemic control affects lathosterol and cholestanol ratios to
      cholesterol and their distribution in lipoproteins. Cholesterol and the non
      cholesterol sterols were assayed directly from serum, and free and ester
      fractions after thin-layer chromatographic separation of lipoprotein sterols with
      gas-liquid chromatography. After the 2-6 months follow-up, the mean value of
      HbA1(c) decreased from 10.8% to 8.6% (p=0.001). Even though the concentrations of
      serum and lipoprotein cholesterol remained unchanged, the serum lathosterol to
      cholesterol ratio increased by 28% (p<0.05) and the lathosterol/cholestanol
      proportion by 23% (p<0.05). The ratios of total and esterified lathosterol to
      cholesterol in serum, chylomicrons and LDL, and free lathosterol to cholesterol
      in serum and IDL, were negatively associated with HbA1(c) at baseline and after
      follow-up, suggesting that the better glycemic control, the higher was
      cholesterol synthesis. The absorption markers were less consistently associated
      with HbA1(c). About half of the serum lathosterol and cholestanol was carried in
      LDL and one-fourth to one-fifth in HDL, but the lathosterol ratios were roughly
      similar in all lipoproteins. In contrast, cholestanol accumulated in chylomicrons
      and HDL. Glycemic control did not affect the distributions of lathosterol and
      cholestanol. In conclusion, improvement in glycemic control increased cholesterol
      synthesis, but had no effect on cholesterol absorption as measured by the serum
      or lipoprotein cholestanol to cholesterol ratio. From a clinical point of view,
      the better the glycemic control, the more antiatherogenic cholesterol metabolism
      may be in type 1 diabetes.

PMID- 16996520
TI  - Serum tissue inhibitor of metalloproteinases-1 and higher risk features of
      coronary plaque: a volumetric multivessel intravascular ultrasound study.
AB  - AIMS: The purpose of this study was to determine the relationship between higher
      risk features of coronary plaque and serum levels of matrix metalloproteinase
      (MMP) family enzymes in the stable angina patients. METHODS AND RESULTS: In 36
      patients, 75 coronary lesions were assessed by intravascular ultrasound. For each
      of the plaques remodelling index, mean calcium arc and plaque burden were
      measured. Positive remodelling and the values of the calcium arc and plaque
      burden above the respective medians were regarded as the higher-risk features and
      summarised for each lesion. Serum levels of MMP-2, -3, -7, -9, and tissue
      inhibitor of MMP (TIMP)-1 and -2 were measured in all patients. TIMP-1 level was
      the independent predictor of presence of a lesion with positive remodelling (OR
      1.032; 95% CI: 1.004-1.061) and of a lesion with higher plaque burden (OR 1.026;
      95% CI: 1.003-1.049) in a given patient. Whereas, MMP-2 level was an independent
      predictor of presence of a lesion with higher calcium arc (OR 1.035; 95% CI:
      1.001-1.071). TIMP-1 level (p=0.003) was also an independent predictor of a
      number of higher-risk features in the highest-risk plaque in a given patient.
      CONCLUSIONS: TIMP-1 level correlates with clustering of plaque features
      associated with higher risk of complications in stable angina patients.

PMID- 16996521
TI  - A 1,3-diacylglycerol-rich oil induces less atherosclerosis and lowers plasma
      cholesterol in diabetic apoE-deficient mice.
AB  - OBJECTIVE: Recent studies have demonstrated that 1,3-diacylglycerol (1,3-DAG) has
      several metabolic advantages over triacylglycerol (TAG) in humans and in animal
      models despite both oils having a similar fatty acid composition. In our current
      study, we have examined the effects of long-term feeding of a 1,3-DAG-rich oil on
      the dyslipidemia and atherosclerosis in the experimental model of the diabetic
      apolipoprotein E (apoE)-deficient mouse that develops accelerated
      atherosclerosis. METHODS AND RESULTS: Diets containing 1,3-DAG-rich oil or TAG
      oil were administered to control non-diabetic apoE-dificient and diabetic apoE
      deficient mice for 20 weeks. In diabetic apoE-deficient mice, 1,3-DAG reduced the
      extent of atherosclerotic lesions in the aortic arch and thoracic aorta by 37 and
      44%, respectively, compared to TAG. Further, in diabetic apoE-deficient mice,
      plasma total cholesterol and triglyceride levels were significantly lower in the
      1,3-DAG-fed group than in the TAG-fed group. This occurred partially through an
      apparent reduction in the size of triglyceride-rich lipoproteins but not
      apparently by reducing the number of lipoprotein particles. By contrast the
      control non-diabetic apoE-deficient mice showed no differential responses to the
      type of oil at least over 20 weeks. CONCLUSIONS: We have demonstrated that
      dietary 1,3-DAG-rich oil reduced atherosclerosis in diabetic apoE-deficient mice,
      and was associated with reduction in plasma cholesterol especially within larger
      triglyceride-rich lipoproteins.

PMID- 16996522
TI  - Detection of free elastin-derived peptides among diabetic children.
AB  - Elastin breakdown products are found in the serum of all human subjects. The
      presence of these elastin-derived peptides (EDP) and the corresponding antibodies
      in circulation leads to formation of circulating immune complexes (CIC). The aim
      of this study was to determine if serum level of free-EDP (unbound in CIC)
      correlate with the development of microvascular complications in children with
      Type 1 (insulin-dependent) diabetes mellitus. To this end we used a method for
      detecting immune complexes (CIF-ELISA) in combination with an ELISA for detection
      of EDP. The levels of free EDP were studied in sera of 81 diabetic children (mean
      age 13.46+/-3.51 years, diabetes duration 5.17+/-4.21 years). Forty-two of the
      children had vascular complications (group 1) and 39 were without vascular
      complications (group 2). Twenty-one healthy children (mean age 12.6+/-2.47 years)
      were used as controls. Diabetics showed significantly higher levels of free EDP
      (68.1+/-25 ng/ml versus 51+/-12.5 ng/ml; p=0.003) compared to the control group.
      In group 1, free EDP showed significantly higher levels than controls (78.9+/
      25.6 ng/ml versus 51+/-12.5 ng/ml; p=0.0001). About 38 of 81 (47%) patients were
      positive for free EDP (30/42--71% in group 1 and 8/39--21% in group 2). Free EDP
      levels in all diabetics showed a correlation with insulin dose (r=0.23; p=0.041),
      and microalbuminuria (r=0.57; p=0.0001). Patients who had vascular pathology
      showed a correlation of free EDP with microalbuminuria (r=0.41; p=0.0081),
      retinopathy (r=0.32; p=0.041), insulin dose (r=0.37; p=0.02), HbA1c (r=0.35;
      p=0.03), systolic blood pressure (r=0.30; p=0.045) and total cholesterol (r=0.36;
      p=0.02). These findings suggest that elevated levels of free EDP are associated
      with the development of diabetic vascular complications in children.

PMID- 16996523
TI  - Smoking and postprandial triglycerides are associated with vascular disease in
      patients with type 2 diabetes.
AB  - AIMS: To determine whether postprandial lipid levels are markers of clinical and
      subclinical macrovascular disease in a select group of patients with type 2
      diabetes. METHODS: We recruited 119 local patients with type 2 diabetes and
      moderate metabolic control (HbA1c <8%). The patients were being treated with
      dietary measures and/or oral antihyperglycemic therapy. No patient was receiving
      lipid-lowering therapy. A history of cardiovascular events was recorded and the
      ankle-arm index was measured to assess subclinical peripheral artery disease. The
      patients underwent a lipid analysis after a 12-h fast and 4h after a mixed
      breakfast (50 g of fat, 40 g of carbohydrates). RESULTS: The patients with
      clinical and subclinical macrovascular disease had a greater history of smoking,
      a longer disease duration, and higher serum creatinine levels. The groups with
      macroangiopathy had lower postprandial concentrations of HDL cholesterol (p<0.05)
      and a trend towards lower fasting levels of HDL cholesterol (p=0.08) and higher
      fasting and postprandial levels of triglycerides (p=0.07). Multivariate analysis
      showed the presence of vascular (both clinical and subclinical) disease to be
      significantly associated with smoking (OR 3.06; 95% CI, 1.15-8.4), disease
      duration (for each year, OR 1.12; 95% CI, 1.03-1.22) and postprandial levels of
      triglycerides (for each 50mg, OR 1.73; 95% CI, 1.13-2.65). CONCLUSIONS: In our
      diabetic patients, the postprandial level of triglycerides 4h after a fatty
      breakfast, though not fasting lipids, plus smoking and disease duration were
      independently associated to clinical and subclinical macrovascular disease.

PMID- 16996524
TI  - Differences in allele frequencies of ACE I/D polymorphism between Northern and
      Southern Europe at different ages.

PMID- 16996525
TI  - Chromatographic quantitation at losses of analyte during sample preparation.
      Application of the modified method of double internal standard.
AB  - Known methods of quantitative chromatographic analysis (calibration, external
      standard, internal standard and standard addition) require the application of
      sample preparation techniques without significant losses of analytes. If this
      condition cannot be satisfied, the compensation of these losses should be
      provided. The modification of known method of quantitative chromatographic
      analysis (double internal standard), implying the addition of two homologues
      (previous and following) of target analytes as internal standards into initial
      samples is considered. This approach permits us to compensate significant losses
      both analytes and standards at all stages of sample preparation. The advantages
      of this method are demonstrated on the examples of liquid-liquid extraction, head
      space analysis (HSA), distillation of volatile compounds with volatile solvents
      (concentration in condensates) and evaporation of volatile solvents
      (concentrating in the residues of solvents). In all cases the application of two
      homologues as internal standards provides accurate results (the typical relative
      errors are within 1-6%) at the values of a factor of composition distortion of
      initial samples (K', the definition is suggested) from 0.2 up to 4. These results
      are in accordance with general relationships between variations in any
      physicochemical properties of organic compounds within homologous series. The
      single found exception was the evaporation of volatile solvents (the open phase
      transition process) when to get the results with relative errors not more then
      +10% requires the minimal changes in the composition of initial samples (K'
      values should not be more then approximately 1.5).

PMID- 16996527
TI  - Determination of the neuropeptides arginine vasotocin and isotocin in brains of
      three-spined sticklebacks (Gasterosteus aculeatus) by off-line solid phase
      extraction-liquid chromatography-electrospray tandem mass spectrometry.
AB  - A method based on solid phase extraction (SPE) followed by liquid chromatography
      electrospray ionisation tandem mass spectrometry for the determination of the
      nonapeptides arginine vasotocin (AVT) and isotocin (IT) in brains of three-spined
      sticklebacks (Gasterosteus aculeatus) is described. Separation and detection were
      optimized using synthetic standards. Limits of detection (LOD) for standard
      solutions were 160 pg mL(-1) for AVT and 250 pg mL(-1) for IT. The SPE procedure
      hardly affected the LODs for standard solutions. Mainly because of ion
      suppression, LODs for AVT and IT in brains were approximately 5 and 25 pg mg(-1),
      respectively. The concentrations determined in the brain of several fishes ranged
      from 10 to 500 pg mg(-1) for AVT and from 400 to 4000 pg mg(-1) for IT.

PMID- 16996528
TI  - Characterisation of Stevia rebaudiana by comprehensive two-dimensional liquid
      chromatography time-of-flight mass spectrometry.
AB  - Comprehensive two-dimensional liquid chromatography (LC x LC) connected on-line
      to electrospray ionisation time-of-flight mass spectrometry (ESI-TOF-MS) was
      employed for analysis of aqueous extract of Stevia rebaudiana. Different
      combinations of strong cation-exchange (SCX), amino (NH2), and octadecyl siloxane
      (C18) stationary phases were tested in the separation of all nine known sweet
      Stevia glycosides. A combination of C18 as the first-dimension column and NH2 as
      the second-dimension column fully separated all the glycosides from the matrix.
      The method proved to be quantitative and repeatable. The limit of detection
      (S/N=3) for stevioside, a widely used natural sweetener, was 43.4 ng/g in dry
      leaves. The RSD for retention times was <0.1% and that of peak areas 4.5%.

PMID- 16996529
TI  - Validation of a diffusive sampling method for airborne low-molecular isocyanates
      using 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole-impregnated filters and liquid
      chromatography-tandem mass spectrometry.
AB  - A diffusive sampling method for the determination of low-molecular isocyanates as
      their 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole (NBDPZ) derivatives using
      tandem mass spectrometry (MS/MS) after atmospheric pressure chemical ionisation
      (APCI) is presented. Isocyanic acid (ICA), methyl isocyanate (MIC), ethyl
      isocyanate (EIC) and phenyl isocyanate (PhIC) are collected on NBDPZ-impregnated
      polystyrene divinyl benzene (SDB) filter tapes. The method was validated for MIC,
      EIC and PhIC for concentrations between 0.5 and 50 ppb at relative humidity (RH)
      conditions from 10 up to 90%. Validation was carried out by active sampling using
      1-(2-methoxyphenyl)piperazine (2-MP) as derivatising agent. Sampling periods
      applied were between 15 min and more than 8 h. The sampling rates were determined
      to be 21.0 mL/min for MIC with a relative standard deviation (RSD) of 9.0% for
      184 samplers, 15.6 mL/min for EIC (RSD 11.6%; N = 154) and 11.5 mL/min for PhIC
      (RSD 8.4%; N = 87). The limits of quantification were 1.4 ppb for MIC and 1.3 ppb
      for EIC and PhIC applying 15 min sampling periods. Owing to high background
      signals, isocyanic acid could only be determined when it was present in
      concentrations in the high ppb range.

PMID- 16996530
TI  - Determination of terpenes in tequila by solid phase microextraction-gas
      chromatography-mass spectrometry.
AB  - Solid phase microextraction and capillary gas chromatography-mass spectrometry
      were used for the determination of seven terpenes in tequila. The method was
      selected based on the following parameters: coating selection (PA, PDMS, CW/DVB,
      and PDMS/DVB), extraction temperature, addition of salt, and extraction time
      profile. The extraction conditions were: PDMS/DVB fiber, Headspace, 100% NaCl, 25
      degrees C extraction temperature, 30 min extraction time and stirring at 1200
      rpm. The calibration curves (50-1000 ng/ml) for the terpenes followed linear
      relationships with correlation coefficients (r) greater than 0.99, except for
      trans,trans-farnesol (r = 0.98). RSD values were smaller than 10% confirmed that
      the technique was precise. Samples from 18 different trade brands of "Aged"
      tequila analyzed with the developed method showed the same terpenes in different
      concentrations. The analytical procedure used is selective, robust (more than 100
      analyses with the same fiber), fast and of low-cost.

PMID- 16996531
TI  - Trends in detection of warfare agents. Detection methods for ricin,
      staphylococcal enterotoxin B and T-2 toxin.
AB  - An overview of the different detection methods available for ricin,
      staphylococcal enterotoxin B (SEB) and T-2 toxin is presented here. These toxins
      are potential biological warfare agents (BWA). The aim of this review is not to
      cover all the papers that had been published but rather to give an overall
      picture of the trend in the detection methodologies for potential biological
      warfare agents as we do see the emerging threats from these three toxins. The
      advantages and disadvantages of each methodology as well as the detection limit
      will be reviewed. It seems that mass spectrometry has created a niche for
      analysis of proteinaceous toxins, ricin and SEB as well as molecular toxin, T-2
      toxin given its high sensitivity, high selectivity, high specificity and
      capability to identify and quantify unknown agents simultaneously in a short time
      frame. But its main drawbacks are its sophisticated instrumentation and its high
      cost. Improvised immunoassay may be an alternative.

PMID- 16996532
TI  - Viscosity measurements of methanol-water and acetonitrile-water mixtures at
      pressures up to 3500 bar using a novel capillary time-of-flight viscometer.
AB  - A new type of viscometer based on the Poiseuille flow principle has been
      developed that is capable of measuring solution viscosities at ultrahigh
      pressures. The capillary time-of-flight (CTOF) viscometer has been used to
      measure the viscosity of methanol-water and acetonitrile-water mixtures in decade
      volume% increments from atmospheric pressure to 3500 bar (50,000 psi), at 25
      degrees C. This instrument works by utilizing a relatively small pressure drop
      (approximately 200 bar) across a capillary which has both inlet and outlet
      pressurized so that the average column pressure can be significantly elevated (up
      to 3500 bar). Measurements from the CTOF viscometer match high-pressure viscosity
      data collected previously using falling-body viscometers of the Bridgman design.
      This manuscript serves to bring viscosity data at ultrahigh pressures for the two
      most common liquid chromatographic mobile phases into the chromatographic
      literature.

PMID- 16996533
TI  - Modelling the shrinkage in pigmented coatings during drying: a stick-slip
      mechanism.
AB  - Pigmented coatings, used to improve optical and printing properties, are applied
      to fibrous paper substrates as slurry, which then dries. We have elucidated the
      mechanism of the shrinkage which occurs during drying. The void space of the dry
      coating layers and their effective solid skeletal elements were modelled using
      the porous network simulation software Pore-Cor. The water-filled porous
      structures at the beginning of the shrinking process were modelled by creating
      simulated structures with the same effective skeletal element size distribution
      as the dry ones, but with higher given porosity to account for the water present.
      The capillary forces acting on the surface of the drying coating were calculated
      for the model structures and found to be orders of magnitude larger than the
      experimentally measured shrinkage forces. The shrinkage process was therefore
      postulated as resulting from the effect of capillary forces resisted by a
      discrete stick-slip process. The differences in the visco-elastic properties of
      the slurries also supported this postulate, as did further experimental evidence.

PMID- 16996534
TI  - The effects of carbon dioxide anesthesia and anoxia on rapid cold-hardening and
      chill coma recovery in Drosophila melanogaster.
AB  - Carbon dioxide gas is used as an insect anesthetic in many laboratories, despite
      recent studies which have shown that CO(2) can alter behavior and fitness. We
      examine the effects of CO(2) and anoxia (N(2)) on cold tolerance, measuring the
      rapid cold-hardening (RCH) response and chill coma recovery in Drosophila
      melanogaster. Short exposures to CO(2) or N(2) do not significantly affect RCH,
      but 60 min of exposure negates RCH. Exposure to CO(2) anesthesia increases chill
      coma recovery time, but this effect disappears if the flies are given 90 min
      recovery in air before chill coma induction. Flies treated with N(2) show a
      similar pattern, but require significantly longer chill coma recovery times even
      after 90 min of recovery from anoxia. Our results suggest that CO(2) anesthesia
      is an acceptable way to manipulate flies before cold tolerance experiments (when
      using RCH or chill coma recovery as a measure), provided exposure duration is
      minimized and recovery is permitted before chill coma induction. However, we
      recommend that exposure to N(2) not be used as a method of anesthesia for chill
      coma studies.

PMID- 16996535
TI  - Detection of Mattesia oryzaephili (Neogregarinorida: Lipotrophidae) in grain
      beetle laboratory colonies with an enzyme-linked immunosorbent assay.
AB  - An indirect sandwich enzyme-linked immunosorbent assay (ELISA) for the detection
      of the neogregarine Mattesia oryzaephili was developed with monoclonal
      antibodies. It was used to screen laboratory colonies of Oryzaephilus
      surinamensis, Cryptolestes ferrugineus, C. pusillus, and C. turcicus from the
      United States, Canada, and Australia. All of the colonies except C. turcicus had
      larvae that tested positive with the percent of positives ranging from 0.2 to
      83.9, but only colonies that tested positive had reported population declines.
      This assay will make possible epizootiological studies to assess the impact of M.
      oryzaephili on pest populations.

PMID- 16996536
TI  - First record of the occurrence of "gill disease" in Mytilus edulis trossulus from
      the Gulf of Gdansk (Baltic Sea, Poland).
AB  - We are presenting the first report of the occurrence of "gill disease" in Mytilus
      edulis trossulus from the southern Baltic Sea, Gulf of Gdansk (Poland). The
      disease preliminary diagnosis was based on the presence of white and yellow
      "spots" causing deep indentations in the gills with degeneration, destruction and
      necrosis of gill filaments. Average prevalence of gill erosion in the blue
      mussels population was 15.8%. According to other authors, gill erosion may affect
      over 80% of the bivalve population resulting in mortality rates of up to 40%. The
      origin of the gill erosion remains unknown, but viruses are most likely involved
      in the etiology of these pathological conditions. The disease as such may
      indicate a decrease in the immunological resistance of organisms to infections
      and inflammations directly or indirectly caused by harmful factors in the ambient
      environment. Furthermore, the occurrence of numerous pathologies in bivalves is a
      particular problem in the Gulf of Gdansk being a low biodiversity ecosystem.
      Pathologies reduce bilvalves' reproduction ability, worsen their physiological
      condition and increase their mortality rate. Those factors may also pose a
      significant ecological danger and lead to negative alterations of the ecosystem.

PMID- 16996537
TI  - Intracellular trafficking of the HCMV immunoevasin UL16 depends on elements
      present in both its cytoplasmic and transmembrane domains.
AB  - Expression of the UL16 glycoprotein leads to down-regulation of NKG2D-ligands
      from the surface of the human cytomegalovirus (HCMV)-infected cell. The molecular
      elements responsible for UL16 trafficking and intracellular localization were
      investigated by preparing various chimeric proteins and mutants, using CD8 as a
      reporter molecule. A YQRL motif, present in UL16's cytoplasmic tail was
      functional for internalization, but the presence of the transmembrane domain
      modified the fate of the molecule after internalization. Various elements of the
      transmembrane domain that affected the trafficking of the protein were
      identified; however, their influence was modified in turn by the presence of the
      cytoplasmic tail of UL16. Strikingly, the extremely slow maturation rate of the
      native viral protein was only reproduced by the chimera that contained both
      transmembrane and cytoplasmic regions of UL16. These findings add data to a topic
      of increasing interest and importance: the role of the transmembrane domain of a
      protein in controlling its intracellular trafficking. In addition, they provide a
      new insight into the mechanism of action of the viral immunoevasin UL16.

PMID- 16996539
TI  - Young driver risk in relation to parents' retrospective driving record.
AB  - PROBLEM: Parents are an important potential influence on the driving safety of
      their children. This study examined the relationship of parental driving record
      on male and female offspring's at-fault collision risk. METHOD: Drivers aged 16
      21 on the date of full licensure were selected from driver records and a matching
      process was used to identify putative parents in two-parent households. Poisson
      regression models were developed to predict at-fault collisions of male and
      female youth in the three years following full licensure from parents' at-fault
      collisions, speeding offenses, and other moving offenses in the four years prior
      to children's licensure. One set of models examined the relative risk associated
      with increasing numbers of maternal and paternal at-fault collisions and
      offenses. Other models examined the joint versus separate maternal and parental
      contributions. RESULTS: Controlling for region of residence, both mothers' and
      fathers' at-fault collisions were associated with an increased risk in both male
      and female youth at-fault collisions. Mothers' and fathers' speeding offenses
      were also associated with increased relative risk of at-fault collisions for both
      sons and daughters, while fathers' other moving offenses increased collision risk
      for sons but not daughters. DISCUSSION: Further research is required to identify
      how parental driving risk is transmitted to children. IMPACT ON INDUSTRY: (a)
      Parents of young children should be informed of their role in influencing their
      children's future driving risk; (b) The results identify risk factors that could
      be of interest to licensing authorities and the insurance industry.

PMID- 16996538
TI  - Mutational analysis of sigma70 region 4 needed for appropriation by the
      bacteriophage T4 transcription factors AsiA and MotA.
AB  - Transcriptional activation of bacteriophage T4 middle promoters requires sigma70
      containing Escherichia coli RNA polymerase, the T4 activator MotA, and the T4 co
      activator AsiA. T4 middle promoters contain the sigma70 -10 DNA element. However,
      these promoters lack the sigma70 -35 element, having instead a MotA box centered
      at -30, which is bound by MotA. Previous work has indicated that AsiA and MotA
      interact with region 4 of sigma70, the C-terminal portion that normally contacts 
      35 DNA and the beta-flap structure in core. AsiA binding prevents the
      sigma70/beta-flap and sigma70/-35 DNA interactions, inhibiting transcription from
      promoters that require a -35 element. To test the importance of residues within
      sigma70 region 4 for MotA and AsiA function, we investigated how sigma70 region 4
      mutants interact with AsiA, MotA, and the beta-flap and function in transcription
      assays in vitro. We find that alanine substitutions at residues 584-588 (region
      4.2) do not impair the interaction of region 4 with the beta-flap or MotA, but
      they eliminate the interaction with AsiA and prevent AsiA inhibition and
      MotA/AsiA activation. In contrast, alanine substitutions at 551-552, 554-555
      (region 4.1) eliminate the region 4/beta-flap interaction, significantly impair
      the AsiA/sigma70 interaction, and eliminate AsiA inhibition. However, the 4.1
      mutant sigma70 is still fully competent for activation if both MotA and AsiA are
      present. A previous NMR structure shows AsiA binding to sigma70 region 4,
      dramatically distorting regions 4.1 and 4.2 and indirectly changing the
      conformation of the MotA interaction site at the sigma70 C terminus. Our analyses
      provide biochemical relevance for the sigma70 residues identified in the
      structure, indicate that the interaction of AsiA with sigma70 region 4.2 is
      crucial for activation, and support the idea that AsiA binding facilitates an
      interaction between MotA and the far C terminus of sigma70.

PMID- 16996540
TI  - The neurological consequences of explosives.
AB  - Neurological injuries produced by explosive blasts are the result of a cascade of
      events that begin with the initial explosion and evolve from the secondary,
      tertiary, and quaternary effects that the explosion engenders [Lavonis EJ. Blast
      Injuries. EMedicine.htm]. Only the results of the primary blast are predictable,
      and subsequent actions ripple outward in an increasingly random and chance
      sequence. This article reviews and explains how the ensuing chain of
      circumstances injures the nervous system, and what examining physicians should
      anticipate when they treat these patients.

PMID- 16996541
TI  - Mutation impact on dysferlin inferred from database analysis and computer-based
      structural predictions.
AB  - Dysferlin is a large sarcolemmal protein implicated in the repair of surface
      membrane tears in muscle cells. Mutations in dysferlin result in limb girdle
      muscular dystrophy type 2B and Miyoshi myopathy. Using a cDNA based approach we
      identified eight new pathogenic dysferlin alleles. To better understand how
      missense mutations could lead to reduced or absent dysferlin expression levels,
      we mapped missense mutations from our own and from published databases (n=55) to
      the secondary protein structure of dysferlin, deduced by computerized structural
      prediction tools. We found the protein to be very sensitive to the alteration of
      residues that were predicted to be buried inside the protein structure. We
      identified seven putative C2 domains, one more than commonly reported, of both
      type I and type II topology in dysferlin. Missense mutations often affected those
      structures as well as residues that were highly conserved between members of the
      ferlin family. Thus, alteration of structurally important residues in dysferlin
      could lead to improper folding and degradation of the mutant protein.

PMID- 16996543
TI  - Corruption begets pollution.

PMID- 16996544
TI  - Quality assurance, information tracking, and consumer labeling.
AB  - Reducing marine-based public health risk requires strict control of several
      attributes of seafood products, often including location and conditions of catch
      or aquaculture, processing, and handling throughout the supply chain. Buyers
      likely will also be interested in other attributes of these products such as eco
      friendliness or taste. Development of markets for improved safety, as well as for
      other quality attributes, requires an effective certification and tracking of
      these attributes as well as their communication to buyers. Several challenges
      must be met if labeling, particularly consumer labeling, is to support the
      development of markets for improved seafood safety.

PMID- 16996542
TI  - Oceans and human health: Emerging public health risks in the marine environment.
AB  - There has been an increasing recognition of the inter-relationship between human
      health and the oceans. Traditionally, the focus of research and concern has been
      on the impact of human activities on the oceans, particularly through
      anthropogenic pollution and the exploitation of marine resources. More recently,
      there has been recognition of the potential direct impact of the oceans on human
      health, both detrimental and beneficial. Areas identified include: global change,
      harmful algal blooms (HABs), microbial and chemical contamination of marine
      waters and seafood, and marine models and natural products from the seas. It is
      hoped that through the recognition of the inter-dependence of the health of both
      humans and the oceans, efforts will be made to restore and preserve the oceans.

PMID- 16996545
TI  - Automatic affective stimulus processing is intact after unilateral resection of
      the anterior temporal lobe in humans.
AB  - Only hundreds of milliseconds after an incoming stimulus is perceived, we make an
      evaluation of whether it is good or bad. This evaluation seems to occur
      automatically and can significantly influence behavior. According to several
      functional imaging studies, the amygdala, which is localized in the temporal
      lobes of the brain, is an important structure for the automatic processing of
      affective stimuli. To investigate how critical a role the amygdala plays in this
      process, we had 20 participants with unilateral resection of the temporal lobe
      and 20 controls perform an affective priming task. Both controls and patients
      demonstrated shorter response latencies on trials where prime and target had the
      same valence than on trials where prime and target had the opposite valence. This
      finding is generally known as the affective priming effect and is considered to
      reflect automatic stimulus evaluation. More specifically, it is assumed that the
      valence of the prime stimulus is activated automatically and exerts an influence
      on the speed by which the target stimulus is evaluated. Given that the affective
      priming effect is equally large in both groups, our results suggest that the
      automatic processing of stimulus valence is intact in participants who sustained
      unilateral resection of the temporal lobe.

PMID- 16996546
TI  - Brainstem mechanisms integrating gut-derived satiety signals and descending
      forebrain information in the control of meal size.
AB  - Ingestive behavior is controlled by a complex interplay between signals conveying
      availability of (1) potentially ingestible food in the environment, (2)
      digestible food in the alimentary canal, (3) circulating fuels and (4) stored
      fuels. Each of these four classes of signals interact with specific sensors and
      neural circuits whose integrated output determines when food intake is initiated
      and when it is stopped. Because the final common path responsible for oromotor
      control is contained within complex neural pattern generators within the
      brainstem and is intimately linked to sensory information from the alimentary
      canal, at least part of the integration between the four classes of signals is
      thought to take place at the level of the caudal brainstem. Here we show that
      CCK, representing a class 2, or direct signal, and MC4-melanocortin receptor
      activity, representing a second order class 3/4, or indirect signal, converge in
      the nucleus of the solitary tract where they modulate activity of the mitogen
      activated, extracellular-signal regulated kinases 1 and 2 (ERK) pathway to
      determine the level of satiation. Blockade of this signaling pathway attenuates
      suppression of deprivation-induced food intake by intraperitoneal CCK and fourth
      ventricular MTII injection. Additional findings suggest that specific ERK
      phosphorylation sites on ion channels and enzymes involved in catecholamine
      synthesis of NTS neurons may be involved in ERK-mediated satiation and meal
      termination. Longer-term downstream effects of ERK activation might involve CREB
      mediated gene transcription known to produce plasticity changes in neurocircuitry
      that could determine inter-meal intervals and the size of future meals.

PMID- 16996547
TI  - Posttraining epinephrine treatment reduces the need for extensive training.
AB  - We studied whether posttraining epinephrine accelerates the process of
      acquisition, and whether this effect leads to an enduring high level of
      performance on a long-term memory test (20 days). Rats were submitted to daily
      massed (30 trials) two-way active avoidance conditioning sessions followed by
      systemic epinephrine (0.01 mg/kg) or vehicle, until achieving a learning
      criterion (80% avoidances in one single session, maximum 14 sessions). By the
      sixth session, 78% of the animals with posttraining epinephrine attained the
      learning criterion compared to only the 23% of the rats in the vehicle group.
      Considering the whole acquisition phase, all the epinephrine treated animals, but
      only 66.67% in the vehicle group, reached the criterion. On the retention test,
      both groups maintained the level of performance reached at the end of the
      acquisition phase. We conclude that epinephrine accelerates the process of
      acquisition by enhancing memory consolidation, and that this effect might be
      especially useful in high demanding learning tasks, or for animals with low
      learning capacities.

PMID- 16996548
TI  - Diterpene resin acids in conifers.
AB  - Diterpene resin acids are a significant component of conifer oleoresin, which is
      a viscous mixture of terpenoids present constitutively or inducibly upon
      herbivore or pathogen attack and comprises one form of chemical resistance to
      such attacks. This review focuses on the recent discoveries in the chemistry,
      biosynthesis, molecular biology, regulation, and biology of these compounds in
      conifers.

PMID- 16996549
TI  - Molecular cloning and functional identification of a ribosome
      inactivating/antiviral protein from leaves of post-flowering stage of Celosia
      cristata and its expression in E. coli.
AB  - A full-length cDNA clone, encoding a ribosome inactivating/antiviral protein
      (RIP/AVP) was isolated from the cDNA library of post-flowering stage of Celosia
      cristata leaves. The full-length cDNA consisted of 1015 nucleotides, with an open
      reading frame encoding 283 amino acids. The deduced amino acid sequence had a
      putative active site domain conserved in other ribosome inactivating/antiviral
      proteins (RIPs/AVPs). The coding region of the cDNA was amplified by polymerase
      chain reaction (PCR), cloned and expressed in Escherichia coli as recombinant
      protein of 72 kDa. The expressed fusion product was confirmed by Western analysis
      and purification by affinity chromatography. Both the recombinant protein (reCCP
      27) and purified expressed protein (eCCP-27) inhibited translation in rabbit
      reticulocytes showing IC50 values at 95 ng and 45 ng, respectively. The native
      purified nCCP-27 has IC50 at 25 ng. The purified product also showed N
      glycosidase activity towards tobacco ribosomes and antiviral activity towards
      tobacco mosaic virus (TMV) and sunnhemp rosette virus (SRV).

PMID- 16996550
TI  - Experimental and mathematical modeling methods for the investigation of
      toxicological interactions.
AB  - While procedures have been developed and used for many years to assess risk and
      determine acceptable exposure levels to individual chemicals, most cases of
      environmental contamination can result in concurrent or sequential exposure to
      more than one chemical. Toxicological predictions of such combinations must be
      based on an understanding of the mechanisms of action and interaction of the
      components of the mixtures. Statistical and experimental methods test the
      existence of toxicological interactions in a mixture. However, these methods are
      limited to experimental data ranges for which they are derived, in addition to
      limitations caused by response differences from experimental animals to humans.
      Empirical methods such as isobolograms, median-effect principle and response
      surface methodology (RSM) are based on statistical experimental design and
      regression of data. For that reason, the predicted response surfaces can be used
      for extrapolation across dose regions where interaction mechanisms are not
      anticipated to change. In general, using these methods for predictions can be
      problematic without including biologically based mechanistic descriptions that
      can account for dose and species differences. Mechanistically based models, such
      as physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models,
      include explicit descriptions of interaction mechanisms which are related to
      target tissues levels. These models include dose-dependent mechanistic hypotheses
      of toxicological interactions which can be tested by model-directed experimental
      design and used to identify dose regions where interactions are not significant.

PMID- 16996551
TI  - Toxinology in Australia's colonial era: a chronology and perspective of human
      envenomation in 19th century Australia.
AB  - The medical management of those envenomed by snakes, spiders and poisonous fish
      in Australia featured extensively in the writings 19th century doctors,
      expeditioners and anthropologists. Against the background of this introduced
      medical doctrine there already existed an extensive tradition of Aboriginal
      medical lore; techniques of heat treatment, suction, incision and the application
      of plant-derived pharmacological substances featured extensively in the
      management of envenomed victims. The application of a hair-string or grass-string
      ligature, suctioning of the bite-site and incision were practised in a variety of
      combinations. Such evolved independently of and pre-dated such practices, which
      were promoted extensively by immigrant European doctors in the late 19th century.
      Pacific scientific toxinology began in the 17th century with Don Diego de Prado y
      Tovar's 1606 account of ciguatera. By the end of the 19th century more than 30
      papers and books had defined the natural history of Australian elapid poisoning.
      The medical management of snakebite in Australia was the focus of great
      controversy from 1860 to 1900. Dogmatic claims of the supposed antidote efficacy
      of intravenous ammonia by Professor G.B. Halford, and that of strychnine by Dr.
      Augustus Mueller, claimed mainstream medical attention. This era of potential
      iatrogenic disaster and dogma was brought to a conclusion by the objective
      experiments of Joseph Lauterer and Thomas Lane Bancroft in 1890 in Brisbane; and
      by those of C.J. Martin (from 1893) and Frank Tidswell (from 1898), both of
      Sydney. The modern era of Australian toxinology developed as a direct consequence
      of Calmette's discovery, in Paris in 1894, of immune serum, which was protective
      against snakebite. We review the key contributors and discoveries of toxinology
      in colonial Australia.

PMID- 16996552
TI  - Measurement of acoustic output power in a traveling wave engine.
AB  - We built and tested a double-loop thermoacoustic cooler consisting of an engine
      loop, a branch resonator, and a cooler-loop. The cooling power of 6.4 W was
      obtained at the cooling temperature of 0 degrees C, when the input heat power of
      416 W was supplied to the engine-loop. We measured the acoustic power and found
      that the output power emitted from the engine-loop was 12 W, and that the input
      acoustic power entering the cooler-loop was 6 W.

PMID- 16996553
TI  - The effect of capsid mutations on HIV-1 uncoating.
AB  - Efficient uncoating requires not only an optimal cellular environment, but also
      some intrinsic properties of the viral capsid protein itself. Using an in vitro
      uncoating model, we demonstrated that substitution of each serine residue with
      alanine at the three major phosphorylation sites of HIV-1 capsid protein, i.e.
      Ser-109, Ser-149 and Ser-178, could significantly reduce uncoating activity of
      purified core particles. We also showed that the core stability of mutant viruses
      was lower than that of the wild-type virus so that the lack of efficient
      uncoating of each mutant could not be due to an increase in capsid physical
      stability. However, serine-to-aspartic acid mutation to mimic the negative charge
      of phosphor-serine could not restore either uncoating activity or infectivity,
      and treatment of purified core particles with a phosphatase did not alter the
      uncoating activity. Our data indicated that mutations at phosphoacceptor sites of
      capsid disturbed the uncoating mechanism, but the defect may not be directly
      caused by the lack of phosphate on the core particles undergoing uncoating.

PMID- 16996554
TI  - Time dependence of protective post-exposure prophylaxis with human monoclonal
      antibodies against pathogenic SHIV challenge in newborn macaques.
AB  - In a primate model of postnatal virus transmission, we have previously shown that
      1 h post-exposure prophylaxis (PEP) with a triple combination of neutralizing
      monoclonal antibodies (nmAbs) conferred sterilizing protection to neonatal
      macaques against oral challenge with pathogenic simian-human immunodeficiency
      virus (SHIV). Here, we show that nmAbs can also partially protect SHIV-exposed
      newborn macaques against infection or disease, when given as 12 or 24 h PEP,
      respectively. This work delineates the potential and the limits of passive
      immunoprophylaxis with nmAbs. Even though 24 h PEP with nmAbs did not provide
      sterilizing immunity to neonatal monkeys, it contained viremia and protected
      infants from acute disease. Taken together with our results from other PEP
      studies, these data show that the success of passive immunization depends on the
      nmAb potency/dose and the time window between virus exposure and start of
      immunotherapy.

PMID- 16996555
TI  - Novel single chain antibodies to the prion protein identified by phage display.
AB  - A well defined structure is available for the carboxyl half of the cellular prion
      protein (PrP(c)), while the structure of the amino terminal half of the molecule
      remains ill defined. The unstructured nature of the polypeptide has meant that
      relatively few of the many antibodies generated against PrP(c) recognise this
      region. To circumvent this problem, we have used a previously characterised and
      well expressed fragment derived from the amino terminus of PrP(c) as bait for
      panning a single chain antibody phage (scFv-P) library. Using this approach, we
      identified and characterised 1 predominant and 3 additional scFv-Ps that
      contained different V(H) and V(L) sequences and that bound specifically to the
      PrP(c) target. Epitope mapping revealed that all scFv-Ps recognised linear
      epitopes between PrP(c) residues 76 and 156. When compared with existing
      monoclonal antibodies (MAb), the binding of the scFvs was significantly different
      in that high level binding was evident on truncated forms of PrP(c) that reacted
      poorly or not at all with several pre-existing MAbs. These data suggest that the
      isolated scFv-Ps bind to novel epitopes within the amino-central region of
      PrP(c). In addition, the binding of MAbs to known linear epitopes within PrP(c)
      depends strongly on the endpoints of the target PrP(c) fragment used.

PMID- 16996556
TI  - Spatial vs temporal continuity in view invariant visual object recognition
      learning.
AB  - We show in a 4-layer competitive neuronal network that continuous transformation
      learning, which uses spatial correlations and a purely associative (Hebbian)
      synaptic modification rule, can build view invariant representations of complex
      3D objects. This occurs even when views of the different objects are interleaved,
      a condition where temporal trace learning fails. Human psychophysical experiments
      showed that view invariant object learning can occur when spatial but not
      temporal continuity applies because of interleaving of stimuli, although
      sequential presentation, which produces temporal continuity, can facilitate
      learning. Thus continuous transformation learning is an important principle that
      may contribute to view invariant object recognition.

PMID- 16996557
TI  - Encoding and stability of image statistics in working memory.
AB  - Visual working memory contains a representation of certain image statistics
      (Victor & Conte, 2004), in addition to a pixel-by-pixel representation. Here, we
      show that the representation of statistics is more stable in time (up to 3000 ms)
      than the pixel-by-pixel representation, especially for changes in luminance and
      local high-order statistics, and is not affected by visual masking. Bilaterally
      symmetric arrays and arrays with local correlations are more readily encoded than
      random ones, but a change in the presence of bilateral symmetry, per se,
      contributes only modestly to the ability to detect that an array has changed.

PMID- 16996558
TI  - Subjective appearance of ambiguous structure-from-motion can be driven by
      objective switches of a separate less ambiguous context.
AB  - Two ambiguous transparent structure-from-motion (SFM) stimuli often appear to co
      rotate. Grossmann & Dobbins (2003) reported breakdown of such perceptual coupling
      when one stimulus was made unambiguous (by rendering it opaque), leading them to
      propose that coupling depends generally on differential stimulus ambiguity. In
      contrast, we demonstrate robust stimulus-driven coupling even when one SFM
      stimulus is relatively disambiguated, by using relative-luminance and/or
      binocular-disparity cues. Such context stimuli could induce stimulus-driven
      coupling by disambiguating the transparent stimulus, though critically only when
      the context was clearly non-opaque and coaxial with the ambiguous stimulus. This
      demonstrates long-range information-sharing between separate stimulus
      representations, subject to specific constraints.

PMID- 16996559
TI  - Representations of familiar and unfamiliar faces as revealed by viewpoint
      aftereffects.
AB  - A viewpoint-dependent aftereffect occurs after prolonged viewing of a stimulus of
      a particular orientation, with the result that the test image is perceived to be
      facing away from the adapting orientation. Prior psychophysical work has led to
      the suggestion that the visual brain encodes a limited range of viewpoint
      information with regard to complex images. In this study, we investigated whether
      familiar faces were susceptible to a viewpoint aftereffect. Familiar faces are
      believed to be represented in a view-invariant manner, whereas unfamiliar faces
      are represented in a viewpoint-dependent manner. Adaptation to both familiar and
      unfamiliar faces influenced the perception of viewpoint of subsequent face
      images. However, category-specific transfer of a repulsive viewpoint-dependent
      aftereffect was observed with unfamiliar faces. Our results suggest that neural
      networks that mediate viewpoint information are also involved in view-invariant
      representation of familiar faces.

PMID- 16996560
TI  - Occurrence and removal of selected organic micropollutants at mechanical,
      chemical and advanced wastewater treatment plants in Norway.
AB  - In Norway the combined hydraulic capacity of all domestic wastewater treatment
      plants is relatively equally distributed between three major treatment plant
      types; mechanical, chemical, and combined chemical and biological. The Western
      coast from Lindesnes in the south to the Russian boarder in the North is
      dominated by mechanical treatment plants, constituting approximately 68% of the
      treatment capacity in that area. In the present study we report concentrations
      and removal efficiencies of polycyclic aromatic hydrocarbons (PAHs),
      nonylphenols, phthalates, polybrominated diphenyl ethers (PBDEs) and
      polychlorinated biphenyls (PCBs) found in five Norwegian wastewater treatment
      plants (WWTPs) applying different levels of treatment. Concentrations of organic
      micropollutants in the influents to the WWTPs were generally in the low range of
      what have been reported by others for domestic wastewater in Europe and North
      America. More than 90% removal could be obtained for nonylphenols, PBDEs, and the
      more hydrophobic 4-6 ring PAHs by chemical precipitation, however, biological
      treatment appeared to be necessary for efficient removal of the less lipophilic 2
      and 3 ring PAHs, the medium- to short-chained nonylphenol ethoxylates and diethyl
      phthalate. SigmaPCB(7) was removed by more than 90% by combined
      biological/chemical treatment, while removal efficiency by chemical treatment was
      not possible to estimate due to low inlet concentrations. Low or insignificant
      removals of PAHs, phthalates and nonylphenols with their ethoxylates were
      observed at the mechanical WWTP, which was in accordance with the minuscule
      removal of TOC.

PMID- 16996561
TI  - The Ugi reaction in the generation of new nucleosides as potential antiviral and
      antileishmanial agents.
AB  - 5-Formyl-2'-deoxyuridine-3',5'-diacetate was converted to a small library of 5
      substituted pyrimidine nucleoside N-acylamino acid amides by means of a Ugi
      multicomponent reaction. The reaction allowed introduction of various
      substituents at the acyl moiety, at the amino acid alpha-amide group, and at the
      amino acid carboxyl function. Evaluation of these novel 5-substituted nucleosides
      against vaccinia virus and cowpox virus provided one compound with discernable
      activity against cowpox virus but five- to eightfold less active than the
      Cidofovir standard. More promising activity was seen for the inhibition of
      Leishmania donovani promastigotes. Several synthetic products showed
      antileishmanial activity in the 10(-5)M range. When compared to earlier studies
      demonstrating anti-orthopoxviral and antileishmanial activity of 5-substituted
      pyrimidine nucleosides, these results imply that the 5-(N-acylamino acid amide)
      derivatized pyrimidine nucleosides may possess more steric bulk, greater
      hydrophobicity, and more flexibility than is compatible with these particular
      biological activities.

PMID- 16996562
TI  - Robust lanthanide-based assays for the detection of anti-apoptotic Bcl-2-family
      protein antagonists.
AB  - Anti-apoptotic Bcl-2-family proteins (Bcl-2, Bcl-x(L), Bfl-1, Mcl-1, Bcl-W and
      Bcl-B) have been recently validated as drug discovery targets for cancer, owed to
      their ability to confer tumor resistance to chemotherapy or radiation. The anti
      apoptotic activity of Bcl-2 proteins is due to their ability to heterodimerize
      with their pro-apoptotic counterparts (proteins such as Bad, Bim or Bid) via a
      conserved peptide region termed BH3. Thus, molecules that mimic pro-apoptotic BH3
      domains represent a direct approach to overcoming the protective effects of anti
      apoptotic proteins such as Bcl-2 and Bcl-x(L). Here, we report on the development
      and evaluation of two novel Lanthanide-based assays that are formatted for high
      throughput screening of small molecules capable of antagonizing BH3-Bcl-2
      interactions. The assay conditions, robustness and reproducibility (Z' factors)
      are described. These assays represent useful tools to enable further studies in
      the search for novel, safe and effective anti-cancer agents targeting Bcl-2
      family proteins.

PMID- 16996563
TI  - Exposure of traffic police to Polycyclic aromatic hydrocarbons in Beijing, China.
AB  - Exposure of on-duty traffic police in Beijing to polycyclic aromatic hydrocarbons
      (PAHs) was investigated during the summer, 2004 using a personal sampling
      technique in measuring both particulate and gaseous phase PAHs. The results were
      then compared with those from two control sites away from the street. Exposure
      levels to gaseous and particulate PAHs for the traffic police were found to be
      1525 +/- 759 ngm(-3) and 148 +/- 118 ngm(-3), respectively, representing 2-2.5
      times higher levels than those at the control sites. The daily inhalation
      exposure of the police was estimated to be 277 ngkg(-1)d(-1). Most of the PAHs
      exposure came from the vapor phase, particularly NAP, FLO and PHE. Based on
      calculated PAH diagnostic ratios, the major source of PAHs exposure was from
      vehicle exhaust. The effects of temperature, humidity and atmospheric stability
      on exposure levels are also discussed.

PMID- 16996564
TI  - Gene expression profiling of nasopharyngeal carcinoma reveals the abnormally
      regulated Wnt signaling pathway.
AB  - Nasopharyngeal carcinoma (NPC) is a particularly common malignant disease in
      areas of south China and Southeast Asia. To characterize the gene expression
      profiling of NPC, we detected the gene expression profiles in 22 NPC and 10
      nontumor nasopharyngeal epithelial tissues by complementary DNA microarray. We
      identified 503 genes that were significantly (P < .001) differentially regulated
      between NPC and nontumor nasopharyngeal epithelial tissues. The differentially
      expressed genes are involved in many signaling pathways, such as the Wnt,
      transforming growth factor-beta, and mitogen-activated protein kinase signaling
      pathways. The aberrant expression of the Wnt signaling pathway components, such
      as wingless-type MMTV integration site family, member 5A, Frizzled homolog 7,
      casein kinase IIbeta, beta-catenin, CREB-binding protein, and Dishevelled
      associated activator of morphogenesis 2 was validated on the NPC tissue
      microarrays. The data suggest that the Wnt signaling pathway may be abnormally
      regulated in NPC, which provides insight into the molecular mechanisms of NPC.

PMID- 16996565
TI  - Extracellular matrix proteins and myofibroblasts in granulomas of sarcoidosis,
      atypical mycobacteriosis, and tuberculosis of the lung.
AB  - Sarcoidosis, atypical mycobacteriosis, and tuberculosis are common diseases of
      human lung with a typical feature of formation of granulomas. The structure of
      granulomas has not been elucidated completely. We studied the expression of
      tenascin-C, precursor proteins of collagens I and III, and the presence of
      myofibroblasts in granulomas of sarcoidosis, atypical mycobacteriosis, and
      tuberculosis of human lung. Twenty-five histologic samples of lung were analyzed
      by immunohistochemistry using antibodies to tenascin-C and aminoterminal
      propeptides of collagens I and III. To identify the myofibroblast-type cells in
      granulomas, the sections were also stained with antibodies against alpha-smooth
      muscle actin, vimentin, and desmin. In every case, tenascin-C and precursor
      proteins of collagens I and III were expressed around granulomas. Precursor
      protein of collagen I was expressed also within them. In tuberculosis and
      atypical mycobacteriosis, expression of tenascin-C and precursor protein of
      collagen I was stronger than in sarcoidosis. The cells demarcating granulomas
      and, thus, colocalizing with tenascin-C and both collagen precursors were
      positive for alpha-smooth muscle actin and vimentin, which suggests that these
      cells are myofibroblasts. They were also more abundantly present in tuberculosis
      and atypical mycobacteriosis, as suggested by alpha-smooth muscle actin staining.
      We concluded that tenascin-C and precursor proteins of collagens I and III are
      expressed around granulomas in sarcoidosis, atypical mycobacteriosis, and
      tuberculosis of the lung; and furthermore, their expression colocalize with the
      expression of myofibroblasts. Our results further point to the fact that
      fibrogenesis and matrix turnover is stronger in tuberculosis and atypical
      mycobacteriosis than in sarcoidosis.

PMID- 16996566
TI  - High incidence of microscopic gastrointestinal stromal tumors in the stomach.
AB  - Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms with an
      annual incidence of approximately 10 to 20 per 1 million cases. Although
      pathologists have often observed incidental small GISTs in the stomach resected
      from patients with gastric cancer, no report on the real incidence of gastric
      GISTs is available. In this study, 100 whole stomachs resected from patients with
      gastric cancer were sectioned at 5-mm intervals and hematoxylin and eosin-stained
      slides (a mean of 130 slides for each case) were examined for microscopic GISTs.
      KIT (CD117), CD34, and desmin expression of the incidental tumors was evaluated
      by immunohistochemistry, and genomic DNA extracted from formalin-fixed and
      paraffin-embedded tumor tissues was analyzed for c-kit gene mutations in exon 11.
      In 35 of the 100 whole stomachs, we found 50 microscopic GISTs, all of which were
      positive for KIT and/or CD34 and negative for desmin. Most microscopic GISTs
      (45/50, 90%) were located in the upper stomach. Two of the 25 (8%) microscopic
      GISTs had c-kit gene mutations. Fifty-one leiomyomas with positive expression for
      desmin were observed in 28 of the 100 stomachs. Both leiomyomas and GISTs were
      found in 12 stomachs. These results indicate that microscopic GISTs are common in
      the upper portion of the stomach. Considering the annual incidence of clinical
      GISTs, only few microscopic GISTs may grow into a clinical size with malignant
      potential. Further studies are required to clarify the genetic events responsible
      for the transformation of microscopic GISTs to clinical GISTs.

PMID- 16996567
TI  - Differential expression of ABCF2 protein among different histologic types of
      epithelial ovarian cancer and in clear cell adenocarcinomas of different organs.
AB  - Previously, we reported that ABCF2 protein expression is higher in clear cell
      than serous histotype of ovarian adenocarcinomas and that its expression
      correlates with chemoresponse in patients with clear cell ovarian cancer. In this
      study, we examined ABCF2 protein expression in mucinous, endometrioid, and poorly
      differentiated type of ovarian adenocarcinomas. In addition, ABCF2 expression was
      evaluated in clear cell adenocarcinomas derived from different organs. A total of
      335 epithelial ovarian cancers, 23 clear cell adenocarcinomas of uterine corpus,
      and 34 clear cell adenocarcinomas of kidney were included in this study. ABCF2
      protein expression was determined by immunohistochemistry. The results showed
      that cytoplasmic ABCF2 expression was significantly higher in clear cell-type
      ovarian cancer specimens compared with other types (P < .0001). There was a close
      relationship between nuclear ABCF2 expression levels and age of patients with
      clear cell ovarian cancer. Multivariate logistic regression model also
      demonstrated that cytoplasmic ABCF2 expression was associated with clear cell
      histology (odds ratio, 5.557; 95% confidence interval, 2.694-11.462; P < .0001).
      In addition, both clear cell adenocarcinomas of the ovary and the uterine corpus
      showed significantly higher levels of ABCF2 expression, compared with those of
      the clear cell adenocarcinoma of the kidney (P < .0001). These data suggest that
      ABCF2 protein may be a candidate marker for clear cell adenocarcinomas of the
      ovary and the uterine corpus and may be important for the pathogenesis of these
      diseases.

PMID- 16996568
TI  - Expression of alpha-methylacyl-coenzyme A racemase in dysplastic Barrett's
      epithelium.
AB  - Although identification of epithelial dysplasia in Barrett's esophagus (BE) is
      critically important because of a significant risk of progression to invasive
      adenocarcinoma, the diagnosis of dysplasia may be challenging. Among confounding
      factors are interobserver variability, tangential sectioning, and severe mucosal
      inflammation leading to architectural and cytologic atypia similar to that of
      dysplasia. alpha-methylacyl-coenzyme A racemase (AMACR) is an enzyme involved in
      beta-oxidation of branched fatty acids and an established marker of prostate
      cancer. It is expressed in colon adenomas and adenocarcinomas but not in normal
      colonic epithelium suggesting a role in development of gastrointestinal
      malignancies. We investigated whether expression of AMACR can be used to identify
      dysplasia of BE and to distinguish it from reactive atypia. Ninety-six routinely
      processed biopsy and/or resection specimens (23 negative for dysplasia; 19, low
      grade dysplasia; 22, high-grade dysplasia; 16, reactive atypia; and 16,
      esophageal adenocarcinoma) were immunostained using a monoclonal anti-AMACR
      antibody p504S. AMACR staining was uniformly negative in the groups negative for
      dysplasia and with reactive atypia. Only 2 (11%) of 19 specimens with low-grade
      dysplasia showed positive immunostaning, compared with 14 (64%) of 22 in high
      grade dysplasia group. Of 16 specimens, 12 (75%) showed positive staining for
      AMACR in the adenocarcinoma group. Our data suggest that AMACR immunoreactivity
      is moderately sensitive in identification of high-grade dysplasia in BE and is
      highly specific in distinguishing high-grade dysplasia from reactive atypia.
      Further validation and prospective studies are warranted.

PMID- 16996569
TI  - Pathology of the thyroid in severe acute respiratory syndrome.
AB  - The severe acute respiratory syndrome (SARS) epidemic started in November 2002
      and spread worldwide. The pathological changes in several human organs of
      patients with SARS have been extensively described. However, to date, little has
      been reported about the effects of this infection on the thyroid gland. Femoral
      head necrosis and low serum triiodothyronine and thyroxine levels, commonly found
      in patients with SARS, raise the possibility of thyroid dysfunction. We have
      undertaken this study to evaluate for any potential injury to the thyroid gland
      caused by SARS on tissue samples obtained from 5 SARS autopsies. The terminal
      deoxynucleotidyl transferase-mediated dUPT nick end-labeling assay was performed
      to identify apoptotic cells. The follicular epithelium was found to be damaged
      with large numbers of cells exfoliated into the follicle. The terminal
      deoxynucleotidyl transferase-mediated dUPT nick end-labeling assay demonstrated
      many cells undergoing apoptosis. Follicular architecture was altered and showed
      distortion, dilatation, and collapse. No distinct calcitonin-positive cells were
      detectable in the SARS thyroids. In conclusion, both parafollicular and
      follicular cells were injured. This may provide an explanation both for low serum
      triiodothyronine and thyroxine levels and the osteonecrosis of the femoral head
      associated with patients with SARS. Apoptosis may play a role in the pathogenesis
      of SARS associated coronavirus infection in the thyroid gland.

PMID- 16996570
TI  - The activated nerve growth factor receptor p-TrkA is selectively expressed in
      advanced-stage ovarian carcinoma.
AB  - The objective of this study was to compare the expression of the nerve growth
      factor (NGF) receptors TrkA and p75 in ovarian borderline tumors, International
      Federation of Gynecology and Obstetrics (FIGO) stage I carcinomas and advanced
      stage (FIGO stage III-IV) carcinomas, and to assess a possible association
      between NGF receptor expression and mitogen-activated protein kinase (MAPK)
      activation in borderline tumors and FIGO stage I carcinomas. Sections from 119
      borderline tumors, 57 FIGO stage I invasive ovarian carcinomas, and 56 advanced
      stage carcinomas were evaluated for expression of activated phospho-TrkA (p-TrkA)
      and p75 using immunohistochemistry. MAPK activation was analyzed in stage I
      carcinomas and borderline tumors using phospho-specific antibodies against the
      extracellular-regulated kinase (p-ERK), the high osmolarity glycerol response
      kinase (p-p38), and the c-jun amino-terminal kinase (p-JNK). p-TrkA membrane
      expression was significantly more frequent in advanced-stage carcinomas compared
      with both borderline and stage I carcinomas (P < .001). p75 membrane expression
      was comparable in the 3 groups (P > .05). p-ERK and p-p38 expression was
      comparable in borderline and stage I carcinomas, whereas p-JNK was more
      frequently expressed in stage I ovarian carcinomas (P < .001). NGF receptor
      expression showed no association with MAPK activation in borderline and stage I
      carcinomas. In conclusion, expression of biologically active p-TrkA receptor at
      the cell membrane is up-regulated along tumor progression in ovarian carcinoma,
      whereas p75 expression remains unaltered. These data provide further evidence
      regarding the clinical role of p-TrkA in ovarian carcinoma. NGF receptors
      probably signal via MAPK-independent pathways in ovarian carcinoma.

PMID- 16996571
TI  - Medullary carcinoma of the pancreas in a man with hereditary nonpolyposis
      colorectal cancer due to a mutation of the MSH2 mismatch repair gene.
AB  - Pancreatic adenocarcinoma has been reported in kindreds with hereditary
      nonpolyposis colorectal cancer (HNPCC). Medullary carcinoma of the pancreas is a
      recently described rare variant of pancreatic adenocarcinoma. We describe a man
      with colorectal carcinoma who subsequently developed pancreatic medullary
      carcinoma. The tumor displayed microsatellite instability and loss of expression
      of the mismatch repair proteins MSH2 and MSH6. Mutational analysis of the
      mismatch repair genes MLH1 and MSH2 demonstrated a pathogenic nonsense mutation
      within the MSH2 gene, which is consistent with a diagnosis of HNPCC. This report
      adds support to an association between HNPCC and pancreatic adenocarcinoma
      displaying the medullary phenotype, suggesting that medullary features in a
      pancreatic carcinoma may point toward a genetic cancer predisposition. To our
      knowledge, this is the first reported case of medullary carcinoma of the pancreas
      in a patient with HNPCC due to a mutation of the MSH2 gene.

PMID- 16996572
TI  - A close relationship between intestinal metaplasia and Cdx2 expression in human
      gallbladders with cholelithiasis.
AB  - We previously reported a case of a human gallbladder with cholelithiasis
      consisting of intestinal metaplasia with the expression of caudal-related
      homeobox transcription factor (Cdx2). However, it is unclear how often intestinal
      metaplasia and Cdx2 expression occur in human, nontumorous gallbladders with
      cholelithiasis. We studied the incidence of intestinal metaplasia and Cdx2
      expression in human gallbladders with cholelithiasis. Gallbladders were resected
      under laparoscopy from 103 patients with cholelithiasis between September 2003
      and March 2005. The mean age of the patients was 59.6 +/- 15.0 years (range, 22
      92 years). We retrospectively reviewed these cases to look for the presence of
      intestinal metaplasia and the expression of Cdx2. In addition, the
      characteristics of intestinal metaplasia were examined by immunostaining for
      Muc2, chromogranin A, and serotonin. Intestinal metaplasia was found in 11.7%
      (12/103) of the gallbladders with cholelithiasis. The mean ages of patients with
      and without intestinal metaplasia were 60.8 +/- 15.4 and 59.4 +/- 14.9 years,
      respectively. Cdx2, Muc2, chromogranin A, and serotonin were expressed in 91.7%
      (11/12), 91.7% (11/12), 83.3% (10/12), and 50.0% (6/12) in intestinal metaplastic
      mucosa, respectively. Only one case (1.1%) that expressed Cdx2 without intestinal
      metaplasia did not express Muc2, chromogranin A, and serotonin. We found that
      10.7% (11/103) of nontumorous gallbladders resected because of cholelithiasis
      under laparoscopy revealed intestinal metaplasia with Cdx2 expression.

PMID- 16996574
TI  - Additional evidence for bone technology in the southern African Middle Stone Age.
AB  - Few Middle Stone Age sites have yielded convincing evidence for a complex bone
      technology, a behavior often associated with the emergence of modern cultures.
      Here, we review the published evidence for Middle Stone Age bone tools from
      southern Africa, analyze an additional nine bone artifacts recently recovered
      from Middle Stone Age levels at Blombos Cave, describe an unpublished bone tool
      from probable Middle Stone Age levels at Peers Cave, examine a single bone awl
      found at Blombosch Sands (an open site near Blombos Cave), and reappraise marked
      bone artifacts and a bone point recovered from Klasies River. To determine the
      chronological and cultural attribution of these artifacts, document bone
      manufacturing techniques associated with the southern African MSA, and discuss
      the symbolic significance of the markings present on some of these objects we use
      (1) available contextual information; (2) morphometric comparison of Later Stone
      Age, Modern San, and purported Middle Stone Age projectile points; (3) analysis
      of the carbon/nitrogen content of bone tools and faunal remains from Peers and
      Blombos caves; and (4) microscopic analysis of traces of manufacture and use.
      Previously undescribed bone artifacts from Blombos Cave include a massive point
      manufactured on weathered bone, two complete awls and two awl tips manufactured
      on small-sized mammal and bird bone, a probable projectile point with a tang
      manufactured by knapping and scraping, a shaft fragment modified by percussion,
      used as retoucher and bearing a set of incised lines on the middle of the
      periosteal surface, and two fragments with possible engravings. The point from
      Peers Cave can be assigned to the Middle Stone Age and bears tiny markings
      reminiscent of those recorded on projectile points from Blombos and used as marks
      of ownership on San arrow points. The awl from Blombosch Sands and the bone point
      from Klasies River can be attributed to the Later Stone Age. Two notched objects
      from Klasies are attributed to the Middle Stone Age and interpreted as tools used
      on soft material; a third object bears possible deliberate symbolic engravings.
      Although low in number, the instances of bone artifacts attributable to the
      Middle Stone Age is increasing and demonstrates that the bone tools from Blombos
      Cave are not isolated instances. New discoveries of bone tools dating to this
      time period can be expected.

PMID- 16996573
TI  - Coordinate loss of fibroblast growth factor 2 and laminin 5 expression during
      neoplastic progression of mammary duct epithelium.
AB  - Branching morphogenesis in mammary ducts is associated with the expression of a
      number of proteins. These include laminin 5 and basic fibroblast growth factor
      (FGF)-2. Both proteins are lost with malignant transformation of mammary
      epithelium and have causal roles in branching morphogenesis in breast cancer
      cells in vitro. The in vivo relationships of these proteins with each other and
      with the loss of branched structures and mammary ductal dedifferentiation are not
      known. We carried out indirect fluorescence staining on subsets of archived
      pathologic samples from 55 patients, with a total of 140 pathologic entities,
      many with multiple stages of dedifferentiation present on the same cut, using
      antibodies to fibroblast growth factor-2 (FGF-2), fibroblast growth factor
      receptor-1 (FGFR1), and laminin 5 to determine expression. We also used Western
      blots to detect laminin 5 expression in MCF-7, T-47D, and MDA-MB-231 cells
      transfected with vectors constitutively expressing FGF-2 and immunofluorescence
      staining of matrix proteins deposited by these cells to determine export and
      accumulation of laminin 5. FGF-2 and laminin 5 expression were found throughout
      benign and atypical dedifferentiation in mammary tissue samples and were lost
      primarily with transformation to invasive cancer. FGFR1 was expressed in all cell
      types. Cancer cells enforced to express FGF-2 did not have detectable laminin 5
      on Western blot, but matrix proteins deposited in culture did stain positive,
      suggesting accumulation of exported laminin 5. Data suggest roles for FGF-2 and
      laminin 5 in ductal integrity during mammary carcinogenesis, with loss of
      expression corresponding to loss of ductal structure. In vitro data suggest FGF-2
      as causal in laminin 5 expression and export. Down-regulation of FGF-2 during
      transformation may contribute to loss of laminin 5 expression.

PMID- 16996575
TI  - Early Holocene human skeletal remains from Sumidouro Cave, Lagoa Santa, Brazil:
      history of discoveries, geological and chronological context, and comparative
      cranial morphology.
AB  - In this work, we present new evidence supporting the idea that the first
      Americans were very distinct from late and recent Native Americans and Asians in
      terms of cranial morphology. The study is based on 30 early Holocene specimens
      recovered from Sumidouro Cave (Lagoa Santa region, central Brazil) by Peter Lund
      in 1843. Sumidouro is the largest known collection of Paleoindian skulls deriving
      from a single site. Six different multivariate statistical methods were applied
      to assess the morphological affinities of the Sumidouro skulls in comparison to
      Howells' worldwide extant series and late archaic Brazilian series (Base Aerea
      and Tapera). The results show a clear association between Sumidouro and Australo
      Melanesians and none with late Asian and Amerindian series. These results are in
      accordance with those of previous studies of final Pleistocene/early Holocene
      human skulls from South, Central, and North America, attesting to a colonization
      of the New World by at least two different, succeeding biological populations: an
      early one with a cranial morphology similar to that found today in the African
      and Australian continents, and a later one with a morphology similar to that
      found today among northeastern Asians.

PMID- 16996576
TI  - Hominid exploitation of the environment and cave bear populations. The case of
      Ursus spelaeus Rosenmuller-Heinroth in Amutxate cave (Aralar, Navarra-Spain).
AB  - Cave bears (Ursus deningeri and U. spelaeus) and hominids (Homo heidelbergensis,
      H. neanderthalensis, and H. sapiens) were potential competitors for environmental
      resources (subterranean and open air). Here, we examined the age at death of cave
      bear (Ursus spelaeus Rosenmuller-Heinroth) specimens from Amutxate cave in order
      to shed light on the effect of resource sharing between cave bears and hominids.
      After studying dental wear of the deciduous and permanent dentitions, the
      ontogenetic development of mandibles, and incremental layers of cement (annuli),
      we defined five age groups differentiated by marked development and size gaps.
      Our findings indicate that after hibernating, bears abandoned the den, thereby
      leaving the subterranean environment (caves) free for temporary hominid
      occupation-this would explain the subtle traces of hominid presence in many dens.
      However, a simple calculation based on age at death of subadult and adult cave
      bear specimens in Amutxate cave, extrapolated to the whole cave area, showed that
      the area surrounding this cave hosted bears for at least 9,000 years. This length
      of habitation, quite similar to the time-span derived from amino acid
      racemization and electron spin resonance, indicates that bear populations in the
      Amutxate cave constituted a serious constraint for hominid exploitation of the
      environment.

PMID- 16996577
TI  - Biogeochemical value of managed realignment, Humber estuary, UK.
AB  - We outline a plausible, albeit extreme, managed realignment scenario ('Extended
      Deep Green' scenario) for a large UK estuary to demonstrate the maximum possible
      biogeochemical effects and economic outcomes of estuarine management decisions.
      Our interdisciplinary approach aims to better inform the policy process, by
      combining biogeochemical and socioeconomic components of managed realignment
      schemes. Adding 7494 ha of new intertidal area to the UK Humber estuary through
      managed realignment leads to the annual accumulation of a 1.2 x 10(5) t of 'new'
      sediment and increases the current annual sink of organic C and N, and particle
      reactive P in the estuary by 150%, 83% and 50%, respectively. The increase in
      intertidal area should also increase denitrification. However, this positive
      outcome is offset by the negative effect of enhanced greenhouse gas emissions in
      new marshes in the low salinity region of the estuary. Short-term microbial
      reactions decrease the potential benefits of CO(2) sequestration through gross
      organic carbon burial by at least 50%. Net carbon storage is thus most effective
      where oxidation and denitrification reactions are reduced. In the Humber this
      translates to wet, saline marshes at the seaward end of estuaries. Cost-benefit
      analysis (CBA) was used to determine the economic efficiency of the Extended Deep
      Green managed realignment. When compared to a 'Hold-the-Line' future scenario,
      i.e. the present state/extent of sea defences in the estuary, the CBA shows that
      managed realignment is cost effective when viewed on >25 year timescales. This is
      because capital costs are incurred in the first years, whereas the benefits from
      habitat creation, carbon sequestration and reduced maintenance costs build up
      over time. Over 50- and 100-year timescales, the Extended Deep Green managed
      realignment scenario is superior in efficiency terms. The increased sediment
      accumulation is also likely to enhance storage of contaminant metals. In the case
      of Cu, a metal that currently causes significant water quality issues, Cu removal
      due to burial of suspended sediment in realigned areas translates to a value of
      approximately pounds sterling 1000 a(-1) (avoided clean up costs). Although this
      is not formally included in the CBA it illustrates another likely positive
      economic outcome of managed realignment. Although we focus on the Humber, the
      history of reclamation and its biogeochemistry is common to many estuaries in
      northern Europe.

PMID- 16996578
TI  - Life-threatening cryoglobulinemia: clinical and immunological characterization of
      29 cases.
AB  - OBJECTIVES: To analyze the etiology, clinical presentation, and outcomes of
      patients with life-threatening cryoglobulinemic vasculitis. METHODS: We studied
      209 consecutive patients with cryoglobulinemic vasculitis. A potentially life
      threatening cryoglobulinemia was considered as the development of renal failure,
      vasculitic abdominal involvement, pulmonary hemorrhage, or central nervous system
      involvement. RESULTS: Twenty-nine (14%) patients had life-threatening
      cryoglobulinemic vasculitis. There were 17 women and 12 men, with a mean age of
      57 years. In 17 (59%) patients, life-threatening cryoglobulinemia was the initial
      clinical feature of the disease. The 29 patients had a total of 33 life
      threatening episodes, which included renal failure due to cryoglobulinemic
      glomerulonephritis (n = 18), intestinal vasculitis (n = 8), pulmonary hemorrhage
      (n = 4), and central nervous system involvement (n = 3). In comparison with a
      control group of age-sex-matched patients with milder cryoglobulinemic
      vasculitis, those with severe cryoglobulinemic vasculitis had a higher frequency
      of fever (28% versus 7%, P = 0.017), type II cryoglobulins (100% versus 59%, P =
      0.008), low C3 levels (55% versus 20%, P = 0.001), and a higher mean value of
      cryocrit (11.4% versus 3.3%, P = 0.004). Nineteen (66%) of the 29 patients with
      life-threatening involvement died, with the mortality rate reaching 100% in
      patients with intestinal ischemia and pulmonary hemorrhage. CONCLUSION: Life
      threatening cryoglobulinemic vasculitis was observed in 14% of our patients, with
      almost two-thirds of episodes occurring at the onset of the disease. Fever, high
      cryocrit levels, and low C3 levels were associated with this severe presentation.
      Two-thirds of the patients died, with mortality for pulmonary hemorrhage and
      intestinal ischemia reaching 100%.

PMID- 16996579
TI  - The overlap of Sjogren's syndrome with other systemic autoimmune diseases.
AB  - OBJECTIVE: To analyze the main diagnostic problems caused by the overlap between
      Sjogren's syndrome (SS) and other systemic autoimmune diseases (SAD). METHODS: We
      performed a MEDLINE search for articles published between January 1966 and
      December 2005 that specifically analyzed the overlap between SS and other SAD. We
      identified a list of diagnostic problems in patients with primary SS who had
      features considered typical of other SAD. RESULTS: Clinically, the main
      diagnostic problems occur in SS patients presenting with arthritis, Raynaud
      phenomenon, cutaneous features (subacute cutaneous lupus erythematosus, purpura,
      livedo reticularis, erythema nodosum), interstitial pulmonary disease, and
      cytopenias (leukopenia, thrombocytopenia). Immunologically, antiphospholipid
      antibodies (aPL) and antineutrophil cytoplasmic antibodies (ANCA) are the most
      frequent atypical autoantibodies found in primary SS, with a prevalence ranging
      between 10 and 20%. However, coexisting antiphospholipid syndrome or systemic
      vasculitis is only detected in around 10% of SS patients with aPL or ANCA. Anti
      DNA and anticentromere antibodies have a prevalence of 5 to 10%, but are more
      closely related to clinical and/or laboratory data suggestive of associated
      systemic lupus erythematosus and limited systemic sclerosis, respectively,
      leading to the fulfillment of classification criteria for these diseases in more
      than 25% of cases. CONCLUSION: The wide variety of clinical and immunological
      manifestations of patients with primary SS often overlap with other SAD, making
      the differentiation between primary SS, SS associated with SAD, and SS-like
      presentations of some other SAD difficult. This overlap suggests that the current
      classification criteria are useful in differentiating between autoimmune and non
      autoimmune processes but fail to clearly differentiate among SAD.

PMID- 16996580
TI  - Familial arthropathy in Saudi Arabian children: demographic, clinical, and
      biochemical features.
AB  - BACKGROUND: Familial arthropathy comprises a heterogeneous group of
      arthropathies. It can be either an inflammatory or a noninflammatory condition.
      The worldwide frequency of these disorders is unknown. OBJECTIVE: To study the
      demographic, clinical and biochemical features, and survival of a large series of
      children with familial arthropathies. METHODS: The medical records of children
      who had an arthropathy and a family history of a similar condition at the
      Pediatric Rheumatology Clinic at King Faisal Specialist Hospital-Riyadh between
      1990 and 2005 were reviewed. These included children with familial juvenile
      idiopathic arthritis (FJIA), infantile systemic hyalinosis (ISH), the nodulosis
      arthropathy-osteolysis (NAO) syndrome, and the camptodactyly-arthropathy-coxa
      vara (CAC) syndrome. Familial rheumatic diseases including spondyloarthropathies
      or known syndromes associated with articular manifestations were excluded. In
      each case age, gender, presenting symptoms, laboratory data, diagnostic
      procedures, and provisional and final diagnoses as well as treatment and outcome
      were reviewed. RESULTS: Sixty-two children with various familial arthropathies
      were reviewed. Twelve children (9 female/3 male) with FJIA presented with
      polyarthritis. These children belonged to 4 unrelated families, all of whom were
      from the same geographical area, with 2 families belonging to the same tribe. The
      mean age at onset was 2.4 years, and mean age at diagnosis was 3.5 years. All
      children had high inflammatory markers. Nineteen children (11 male/8 female) with
      ISH presented in the neonatal period with painful joint contractures and typical
      mucocutaneous features. The referral diagnosis was inaccurate in 14 patients.
      Thirteen patients were the product of first-degree cousin marriages, and 5
      families had more than 1 affected child. Radiological findings included
      periosteal reaction and osteolytic lesions. Tissue biopsy was performed in 8
      patients and the findings were consistent with the diagnosis in all 8 patients.
      Despite aggressive management, 16 patients died. The mean age of the remaining 3
      surviving children was 20 months. There were 15 children (9 female/6 male) with
      the NAO syndrome with a mean age at onset of 3.4 years. They were from 7
      unrelated families; 5 families had more than 1 affected child. The referral
      diagnosis was juvenile idiopathic arthritis (JIA). Most children presented with
      painful deformed hands. Eleven children (70%) had advanced osteolytic changes.
      All children had normal inflammatory markers. There were 16 children (11 male/5
      female) with the CAC syndrome who were diagnosed at a mean age of 3.7 years.
      Camptodactyly presented at birth or in first months of life, while other features
      developed in early childhood. JIA was the referral diagnosis. Fourteen children
      had bilateral coxa vara. Two children exhibited symptoms or signs of
      pericarditis. Inflammatory markers were normal in all children. CONCLUSIONS:
      Familial arthropathies are not uncommon conditions which may be easily confused
      with JIA, causing a delay in diagnosis and management. Careful evaluation of a
      child presenting with an arthropathy, particularly in a population where
      consanguinity is common, is required for timely and accurate diagnosis. Overall,
      the prognosis of these conditions remains guarded despite treatment.

PMID- 16996581
TI  - The Con-A-peroxidase method for tissue localization of glucosyl and mannosyl
      groups applied to mouse hepatocytes and chicken erythrocytes.
AB  - A variation of the Concanavalin A (Con-A)-peroxidase labelling method originally
      described by Kiernan [Localization of alpha-D-glucosyl and alpha-D-mannosyl
      groups of mucosubstances with Concanavalin A and horseradish peroxidase.
      Histochemistry 1975;44:39-45] was applied to unsectioned cell preparations, with
      an emphasis on the nuclear localization of glycoproteins. Mouse liver imprints
      and chicken blood smears fixed in acetic acid-ethanol solution were studied.
      Modifications of the method included using increased Con-A concentration, and a
      range of pH values for the Con-A solutions. The strongest Con-A labelling of both
      erythrocytes and hepatocytes was obtained after incubation with Con-A at pH 6.5
      and with Con-A concentrations at least two-fold greater than those used for
      tissue sections. These conditions may alter the Con-A conformation, enabling the
      lectin molecule to enter the cell nucleus and bind to nuclear glycoproteins, thus
      allowing their localization and quantification.

PMID- 16996582
TI  - Reproduction beyond cancer: a message of hope for young women.
AB  - OBJECTIVE: Aggressive chemotherapy and radiotherapy or radical oncological
      surgery in young women with cancer has greatly enhanced these patients' life
      expectancy, but these treatments often cause infertility or premature ovarian
      failure due to a massive destruction of the ovarian reserve. The objective of
      this review is to discuss the effect of the various cancer treatments on
      fertility and present the various fertility sparing operations and fertility
      preservation strategies. METHOD: An extensive survey of the most up-to-date
      literature was performed. RESULTS: This review discusses the impact of current
      cancer treatment on fertility potential and the various surgical and assisted
      reproduction innovations available today for the most common cancers in young
      women. Although the ability to retain reproductive potential is becoming a major
      quality-of-life factor in an increasing number of young female cancer survivors,
      they are still being poorly counseled with regard to the negative impact of the
      treatment on their fertility and on their options for fertility preservation.
      CONCLUSION: As the emerging discipline of fertility preservation is steadily
      attracting increasing interest, developments in the near future promise to be
      very exciting. However, in everyday routine work, better interdisciplinary
      cooperation between gynecological and pediatric oncologists, surgeons,
      immunologists, and endocrinologists is necessary so that individualized options
      for fertility preservation can be offered in advance of surgical procedures or
      cancer treatments.

PMID- 16996583
TI  - A randomized phase III trial of concurrent chemoradiotherapy in locally advanced
      cervical cancer: preliminary results.
AB  - OBJECTIVE: Concurrent chemoradiation is the standard treatment for locally
      advanced cervical cancer. This study was a preliminary result of a randomized two
      arms, prospective, open-label phase III trial comparing the activity and safety
      of the concurrent chemoradiation of Tegafur-Uracil and carboplatin or carboplatin
      alone in locally advanced cervical cancer. MATERIALS AND METHODS: The stage IIB
      IIIB cervical cancer patients were randomized to have Tegafur-Uracil 225
      mg/m(2)/day orally, 5 days a week and carboplatin 100 mg/m(2) IV over 30-60 min,
      weekly on day 1 concurrent with standard radiotherapy (Group A) or carboplatin
      alone concurrent with standard radiotherapy (Group B). RESULTS: Four hundred and
      sixty-nine patients were randomized to Group A (n=234) or Group B (n=235). The
      tumor response at 3-month follow-up time showed no significant difference. The
      only prognostic factor to improve the complete response rate was the hemoglobin
      level. The patients in Group A, who had Hb <10 gm/dL had the relatively better
      change to complete response of 1.48 compared to that in Group B (P 0.025, 95% CI
      1.07, 2.04). No severe toxicity or adverse event had been reported. The median
      follow-up time for Group A and Group B was 12.6 and 11.8 months, respectively.
      There was no statistical difference in PFS and OS. CONCLUSION: Concurrent
      chemoradiation by Tegafur-Uracil and carboplatin showed no difference in tumor
      response rate or treatment toxicity compared to carboplatin alone. The
      combination drugs might have benefit in poor prognostic patients such as the
      baseline Hb <10 gm/dL.

PMID- 16996584
TI  - CA125 level as a predictor of progression-free survival and overall survival in
      ovarian cancer patients with surgically defined disease status prior to the
      initiation of intraperitoneal consolidation therapy.
AB  - OBJECTIVES: Recent data suggest that differences in CA125 levels within the
      normal range may predict progression-free survival (PFS), but limited information
      is available regarding the value of these differences in predicting overall
      survival (OS) in patients with epithelial ovarian cancer. The objective of this
      study was to determine whether CA125 is an independent predictor of OS in
      patients with surgically defined disease status at the end of primary therapy
      prior to intraperitoneal (IP) consolidation chemotherapy. A secondary objective
      was to assess the relationship of CA125 level to PFS. METHODS: Using data from a
      retrospective cohort of 433 patients who received intraperitoneal (IP) therapy
      following primary treatment for ovarian cancer between 1984 and 1998, we
      identified 241 patients with a complete clinical response and CA125 data at the
      time of second-look surgery prior to IP chemotherapy. Patient demographics and
      updated follow-up status were abstracted from medical records. Kaplan-Meier
      survival curves were compared using the log-rank test, and Cox regression models
      were used for multivariate analysis. RESULTS: The majority of patients had
      advanced stage III or IV disease (n=201, 83%) and high-grade histology (n=163,
      68%). Taxane was used as part of primary platinum-based therapy in 56% (n=134) of
      patients, and subsequent IP chemotherapy was platinum-based in 85% (n=206). When
      considered as a continuous variable, CA125 was a predictor of OS (P=0.029). Using
      the median CA125 level in our study group as a cut-off, OS was increased in
      patients with CA125 < or =12 U/ml (median 5.8 years) compared with >12 (3.7
      years) (P=0.0027). CA125 level was an independent predictor of OS (HR: 1.410; 95%
      CI, 1.044, 1.904, P=0.0248) in a multivariate model that included stage
      (P=0.0166), grade (P=0.0001), and findings at second-look surgery (P=0.0003).
      CA125 level was also a predictor of clinical PFS (radiographic or CA125 elevation
      criteria alone) in a subset of 161 patients as a continuous variable (P=0.0036),
      and when divided at the median (< or = or >12; median 2.8 years vs. 1.7 years;
      P=0.0017). CONCLUSIONS: In our study population, CA125 level at the end of
      primary therapy was a predictor of OS and PFS when considered as a continuous
      variable, or when divided at the median (< or = or >12 U/ml). Further prospective
      study is required to optimize clinically significant cut-off values within the
      normal range of CA125 levels for both OS and PFS endpoints.

PMID- 16996585
TI  - (31)P solid-state MAS-NMR spectroscopy of the compounds that form in phosphate
      bonded dental casting investment materials during setting.
AB  - OBJECTIVES: To use (31)P solid-state MAS-NMR to determine which compounds form in
      phosphate-bonded dental casting investment material during setting, when the
      ambient temperature is altered. To determine whether they differ in material
      originating at the center of the mix from material that adheres to the mixing
      bowl wall. METHODS: (1)H high powered decoupled (HPDC) and (1)H cross polarized
      (CP) (31)P solid-state MAS-NMR spectroscopy were used at a resonance frequency of
      121.4MHz to determine molecular structure. Four commercial products were
      examined. Manufacturer's instructions were followed and special liquid used
      without dilution. Ambient temperature was between 18 and 37 degrees C. RESULTS:
      Molecular structures change with ambient temperature and product. Amorphous
      Mg(3)(PO(4))(2) or struvite dominate with newberyite, cattiite, amorphous
      Mg(2)P(2)O(7) and amorphous MgHPO(4) present as minor phases. Exceptionally,
      amorphous MgHPO(4) dominates. Differences in structure were found in material
      taken from the center of the mix compared with that scraped from the bowl wall,
      but the incidence may be specific to the product/mixer combination and not a
      general effect. SIGNIFICANCE: The formation of compounds in phosphate-bonded
      investment can be affected by ambient temperature. This effect and the use of
      material adhering to the bowl wall (instead of that from the center of the mix)
      are possible causes for the unpredictability of setting expansion measurements
      between laboratories. There is variation between products. When phosphate-bonded
      investment is required for casting, a consistent ambient temperature must be used
      and it would be wise to mix sufficient material to avoid scraping the bowl.

PMID- 16996586
TI  - Subsurface degradation of resin-based composites.
AB  - OBJECTIVES: To determine the depth of a degraded subsurface layer produced in
      dental composites as a result of exposure to lactic acid or NaOH, by observing
      the penetration of AgNO(3) solution. METHODS: Specimens were prepared from four
      resin composites; Point 4 (Kerr), Premise (Kerr), Filtek Supreme (3M/ESPE), Ceram
      X (Dentsply), and two polyacid-modified resin composites; Dyract (Dentsply) and
      F2000 (3M/ESPE). The specimens were immersed in distilled water for 1 week,
      transferred to one of three aqueous media at 60 degrees C for 2 weeks; distilled
      water, 0.01mol/L lactic acid or 0.1N NaOH, washed and immersed in 50% (w/w)
      aqueous silver nitrate for 10 days at 60 degrees C and placed in a photodeveloper
      solution. After reduction of the silver, specimens were embedded in epoxy resin,
      sectioned and polished, coated with carbon, and examined by backscattered mode
      scanning electron microscopy. The depth of silver penetration into the degraded
      area was measured from the SEM micrographs. Energy dispersive analysis X-ray
      (EDAX) was used to confirm the presence of silver. RESULTS: NaOH produced the
      greatest depth of degradation and lactic acid the least. Premise showed the
      greatest depth of silver penetration when subjected to NaOH, and Filtek Supreme
      the second with peeling of the surface and cracking, whereas F2000 and Point 4
      showed the least in NaOH and lactic acid. SIGNIFICANCE: ANOVA and Tukey's test
      showed that the depth of silver penetration was material and solution dependent,
      and the differences were significant for most of the materials (P<0.05).

PMID- 16996587
TI  - Calorimetric investigation of the protein-flexible chain polymer interactions and
      its relationship with protein partition in aqueous two-phase systems.
AB  - The binding of polyethyleneglycol of molecular mass 1000, 3300 and 6000 and
      polyethylene-propylene oxide (molecular mass 8400) to lysozyme and ovoalbumin was
      measured by isothermal calorimetric titration. A binding process was found to be
      associated with a saturation effect, which suggests a protein-polymer
      interaction. The proteins showed an affinity for the polymers in the order of
      10(2)M(-1) and it decreased with the increase in the polymer molecular mass. The
      number of polymer molecules bound per protein molecule varied from 0.01 to 0.2
      for polyethyleneglycol 1000, 3300 and polyethylene-polypolypropylene oxide 8400,
      while for polyethyleneglycol 6000 such number got closer to the unity. The
      enthalpic change associated with the binding was positive in the order of 1
      kcal/mol for lysozyme, while ovoalbumin showed values around 2-3 kcal/mol.
      Entropic changes were also positive with values around 17-20 e.u. for ovoalbumin
      and 1-7 e.u. for lysozyme. The heat associated with the protein transfer from a
      buffer to a medium containing the polymer or the salt (a process similar to
      protein partitioning in aqueous two-phase systems) was obtained. These results
      allow the direct calculation of the enthalpic change associated with a protein
      partition process in aqueous two-phase systems without applying the van'tHoff
      equation. In this way, it is possible to calculate the associated true heat when
      the protein is transferred from the bottom to the top phase.

PMID- 16996588
TI  - Segmental bone regeneration using a load-bearing biodegradable carrier of bone
      morphogenetic protein-2.
AB  - Segmental defect regeneration has been a clinical challenge. Current tissue
      engineering approach using porous biodegradable scaffolds to delivery osteogenic
      cells and growth factors demonstrated success in facilitating bone regeneration
      in these cases. However, due to the lack of mechanical property, the porous
      scaffolds were evaluated in non-load bearing area or were stabilized with stress
      shielding devices (bone plate or external fixation). In this paper, we tested a
      scaffold that does not require a bone plate because it has sufficient
      biomechanical strength. The tube-shaped scaffolds were manufactured from
      poly(propylene) fumarate/tricalcium phosphate (PPF/TCP) composites. Dicalcium
      phosphate dehydrate (DCPD) were used as bone morphogenetic protein-2 (BMP-2)
      carrier. Twenty-two scaffolds were implanted in 5mm segmental defects in rat
      femurs stabilized with K-wire for 6 and 15 weeks with and without 10 microg of
      rhBMP-2. Bridging of the segmental defect was evaluated first radiographically
      and was confirmed by histology and micro-computer tomography (microCT) imaging.
      The scaffolds in the BMP group maintained the bone length throughout the duration
      of the study and allow for bridging. The scaffolds in the control group failed to
      induce bridging and collapsed at 15 weeks. Peripheral computed tomography (pQCT)
      showed that BMP-2 does not increase the bone mineral density in the callus.
      Finally, the scaffold in BMP group was found to restore the mechanical property
      of the rat femur after 15 weeks. Our results demonstrated that the load-bearing
      BMP-2 scaffold can maintain bone length and allow successfully regeneration in
      segmental defects.

PMID- 16996589
TI  - Bortezomib therapy response is independent of cytogenetic abnormalities in
      relapsed/refractory multiple myeloma.
AB  - Myeloma patients with unfavorable molecular cytogenetics have a poor prognosis
      irrespective of treatment with conventional chemotherapy or autologous stem cell
      transplant. To investigate whether bortezomib, a new proteasome inhibitor, is
      active in relapsed/refractory myeloma patients with genetic risk factors, we
      evaluated the outcome of 65 patients and correlated the clinical response with
      13q deletion, translocations t(11;14) and t(4;14) and CKS1B amplification as
      detected by interphase cytoplasmic fluorescence in situ hybridization (cIg-FISH).
      Thirty-seven of 61 (61%) evaluable patients had an objective response to
      bortezomib with median progression free (PFS) and overall survivals (OS) of 9.5
      and 15.1 months, respectively. Of 43 cases with evaluable bone marrows, cIg-FISH
      determination of del(13q), t(4;14), t(11;14) and CKS1B amplification was done on
      40, 41, 41 and 37 cases and the frequency of their detection was 35%, 15%, 15%,
      and 32%, respectively. There was no statistically significant difference in
      response to bortezomib for patients with or without 13q deletion (77% versus
      50%), t(4;14) (67% versus 56%), t(11;4) (33% versus 62%), or CKS1B amplification
      (67% versus 57%). Furthermore, there was no statistically significant difference
      in PFS or OS following bortezomib therapy between patients with or without these
      molecular cytogenetic abnormalities. Our data suggest that, in this pilot study,
      bortezomib is an effective salvage therapy for refractory/relapsed myeloma,
      irrespective of genetic risk factors.

PMID- 16996590
TI  - Genetic variation in ICOS regulates mRNA levels of ICOS and splicing isoforms of
      CTLA4.
AB  - Genetic and functional studies suggest that polymorphism in cytotoxic T
      lymphocyte-associated antigen-4 (CTLA4) and inducible costimulator (ICOS) genes,
      both reported to harbour autoimmune susceptibility loci, could regulate the
      immune activation through affecting their expression and splicing of CTLA4. To
      address this, we studied expression of CTLA4 and ICOS and the role of
      polymorphisms in the gene region by measuring the relative amounts of
      transcripts, including the soluble CTLA4 (sCTLA4) splicing isoform in healthy
      volunteers. We combined a physiologically relevant in vitro activation for human
      CD4(+) T lymphocytes and a quantitative RT-PCR. The susceptibility allele CT60G
      in CTLA4 gene was confirmed to be associated with a decreased amount of sCTLA4,
      but only in resting cells. During the T cell activation two genetic variants in
      ICOS gene, IVS1+173T/C and c.1624C/T, affected expression of CTLA4 isoforms and
      ICOS, respectively. We could not confirm that the level of sCTLA4 is down
      regulated following T lymphocyte activation, instead the levels of CTLA4 splicing
      isoforms correlated to each others. Our results indicate that genetic variation
      in this gene region regulates the expression of both CTLA4 and ICOS and not only
      the splicing of sCTLA4 as suggested earlier.

PMID- 16996591
TI  - Initiation of V(D)J recombination in zebrafish (Danio rerio) ovaries.
AB  - The assembly of mammalian antigen receptor genes is a lymphoid-specific process.
      However, rearranged immunoglobulin genes can also be recovered from non-lymphoid
      tissues of cartilaginous fish. This event, known as germline rearrangement, has
      been speculated to arise from recombination-activating gene (RAG)-mediated
      recombination in germ cells. In this report, we demonstrate that zebrafish (Danio
      rerio) oocytes expressing high levels of RAG-RNA can readily initiate
      recombination cleavage at immunoglobulin gene loci, providing direct evidence for
      an ongoing process of attempted germline rearrangement in zebrafish ovaries. This
      attempted rearrangement is largely unproductive, yielding no accumulation of
      germline-joined immunoglobulin genes in zebrafish, which is consistent with their
      general absence in this species. Our data, therefore, substantiate the
      speculation that RAG might have been derived from a transposase, invading germ
      cells of ancient species, and later become a dedicated recombinase only expressed
      in developing lymphocytes.

PMID- 16996592
TI  - Detection and prognostic significance of optic disc hemorrhages during the Ocular
      Hypertension Treatment Study.
AB  - PURPOSE: To compare the rates of detection of optic disc hemorrhages by clinical
      examination and by review of optic disc photographs at the Optic Disc Reading
      Center (ODRC), to assess the incidence of and the predictive factors for disc
      hemorrhages in the annual disc photographs of the Ocular Hypertension Treatment
      Study (OHTS), and to determine whether optic disc hemorrhages predict the
      development of primary open-angle glaucoma (POAG) in the OHTS. DESIGN: Cohort
      study. PARTICIPANTS: Three thousand two hundred thirty-six eyes of 1618
      participants. METHODS: Both eyes of participants were examined for optic disc
      hemorrhages every 6 months by clinical examination, with dilated fundus
      examinations every 12 months, and by annual review of stereoscopic disc
      photographs at the ODRC. MAIN OUTCOME MEASURES: Incidence of optic disc
      hemorrhages and POAG end points. RESULTS: Median follow-up was 96.3 months.
      Stereophotography-confirmed glaucomatous optic disc hemorrhages were detected in
      128 eyes of 123 participants before the POAG end point. Twenty-one cases (16%)
      were detected by both clinical examination and review of photographs, and 107
      cases (84%) were detected only by review of photographs (P<0.0001). Baseline
      factors associated with disc hemorrhages were older age, thinner corneas, larger
      vertical cup-to-disc ratio, larger pattern standard deviation index on perimetry,
      family history of glaucoma, and smoking status. The occurrence of a disc
      hemorrhage increased the risk of developing POAG 6-fold in a univariate analysis
      (P<0.001; 95% confidence interval, 3.6-10.1) and 3.7-fold in a multivariate
      analysis that included baseline factors predictive of POAG (P<0.001; 95%
      confidence interval, 2.1-6.6). The 96-month cumulative incidence of POAG in the
      eyes without optic disc hemorrhage was 5.2%, compared with 13.6% in the eyes with
      optic disc hemorrhage. In eyes with a disc hemorrhage in which a POAG end point
      developed, the median time between the 2 events was 13 months. CONCLUSIONS:
      Review of stereophotographs was more sensitive at detecting optic disc hemorrhage
      than clinical examination. The occurrence of an optic disc hemorrhage was
      associated with an increased risk of developing a POAG end point in participants
      in the OHTS. However, most eyes (86.7%) in which a disc hemorrhage developed have
      not experienced a POAG end point to date.

PMID- 16996593
TI  - Gaze changes with binocular versus monocular viewing in age-related macular
      degeneration.
AB  - PURPOSE: To determine and explain gaze changes during binocular versus monocular
      viewing in patients with age-related macular degeneration (AMD). DESIGN: Cross
      sectional study. PARTICIPANTS: Twenty-nine patients with bilateral late-stage
      AMD. METHODS: Distance acuity and fundus pathologic features were evaluated. Eye
      position was recorded while viewing a circular fixation target under monocular
      and binocular viewing conditions using an infrared eye tracker (SMI Gazetracker,
      SensoMotoric, Germany; Eyelink Software 2.04). Gaze changes were quantified by
      calculating the mean x-coordinate and y-coordinate eye position of the center of
      the bivariate contour ellipse area for a 30-second fixation task under both
      viewing conditions. Retinal loci used for monocular fixation for each eye were
      determined using the scanning laser ophthalmoscope (SLO; SLO 101, Rodenstock,
      Munich, Germany). MAIN OUTCOME MEASURE: Gaze position. RESULTS: Nine patients
      showed no shift in gaze position from monocular to binocular viewing. Three
      patients demonstrated a shift in both eyes, and 17 patients demonstrated a shift
      in only 1 eye. The mean shift was 4.7+/-5 degrees (standard deviation). The shift
      in gaze position in the worse eye was predictive of the distance between the 2
      monocular preferred retinal loci (PRLs; better and worse eye; r(2) = 0.59;
      P<0.0001), whereas there was no association between the shift in gaze position in
      the better eye and distance (r(2) = 0.00; P = 0.91). CONCLUSIONS: Most AMD
      patients shift gaze position in 1 or both eyes when viewing binocularly compared
      with monocularly. These changes suggest that different retinal locations are used
      for fixation under the 2 viewing conditions. The SLO data showed that these
      patients are likely to demonstrate monocular PRLs that fall on noncorresponding
      areas. These results may have implications for the effective development of
      eccentric viewing and binocular behavior of AMD patients.

PMID- 16996594
TI  - Periocular necrotizing fasciitis with visual loss pathogenesis and treatment.
AB  - OBJECTIVE: To illustrate the role of clinically necessary aggressive subcutaneous
      debridement with limited excision of necrotic skin in treating necrotizing
      faciitis, while demonstrating the histopathologic basis of orbital spread and
      blindness complicating this disorder. DESIGN: Observational retrospective case
      series. PARTICIPANTS: Seven consecutive patients cared for by the Eye Plastic and
      Orbital Surgery Services at the University of Michigan and University of Iowa.
      METHODS: Retrospective review of ocular findings, systemic features, management,
      outcome, and histopathology of debrided tissue from 7 patients with periocular
      necrotizing fasciitis. MAIN OUTCOME MEASURES: Patient survival and morbidity.
      RESULTS: Bilateral involvement was present in 6 of the 7 patients. Five patients
      suffered ophthalmic or central retinal artery occlusion with loss of vision. All
      patients underwent extensive debridement of subcutaneous tissue with sparing of
      overlying nonnecrotic skin and intensive systemic antibiotic therapy. Four
      patients required unilateral exenteration. After a mean follow-up of 38 months, 6
      patients were alive; 1 died perioperatively due to septic shock. Histopathology,
      not previously described, showed inflammation to spread preferentially along
      eyelid fibrofatty-fascial tissue planes into the orbit and along orbital fibrous
      septae, leading to intense perivascular inflammation, thrombosis, and ocular
      infarction. CONCLUSIONS: Necrotizing fasciitis is a potentially fatal disease
      that often causes blindness when affecting the periocular region. To reduce
      morbidity and mortality in severe infections, prompt subcutaneous debridement and
      limited resection of necrotic skin are usually necessary.

PMID- 16996595
TI  - Frailty and age-related cataract.
AB  - OBJECTIVE: To determine whether there is an association between age-related
      cataract and frailty that persists after controlling for visual acuity (VA) and
      comorbid conditions. DESIGN: Cross-sectional. PARTICIPANTS: Two thousand three
      hundred seventy Beaver Dam Eye Study cohort members at 10-year (third)
      examination with cataract information. Ninety-nine percent of the population was
      Caucasian. METHODS: Medical history, blood pressures, height, weight, measures of
      frailty, and lens photographs were obtained during the study evaluation. Lens
      photographs were graded according to standardized protocols. MAIN OUTCOME
      MEASURES: Four of frailty (gait time, peak expiratory flow rate, handgrip
      strength, chair stand) and an index combining all 4 measures. RESULTS: After
      controlling for age, age squared, comorbidity index, pack-years, sedentary
      lifestyle, education, and VA, nuclear cataract in women was not associated
      significantly with any frailty measures; in men, nuclear cataract was associated
      with slower gait time (P = 0.01) and a poorer frailty index score (P = 0.01) in
      multivariable analyses. Cortical cataract was associated in women with a lower
      peak expiratory flow rate (P<0.01) and in men with weaker handgrip strength (P =
      0.02) and a poorer frailty index score (P</=0.01) in multivariable analyses.
      Posterior subcapsular cataract in women was associated significantly with a lower
      peak expiratory flow rate (P = 0.01). Nuclear and cortical cataract add
      significant information in explaining frailty index scores in men. CONCLUSIONS:
      Three common types of age-related cataract are associated with some measures of
      frailty independent of VA and systemic comorbidities. It is possible that age
      related cataract may be an indicator of general functional decline in older
      adults.

PMID- 16996596
TI  - Subthreshold grid laser treatment of macular edema secondary to branch retinal
      vein occlusion with micropulse infrared (810 nanometer) diode laser.
AB  - PURPOSE: To compare the effectiveness of subthreshold grid laser treatment (SGLT)
      with an infrared micropulse diode laser with that of threshold grid laser
      treatment (TGLT) for macular edema secondary to branch retinal vein occlusion
      (BRVO). DESIGN: Randomized clinical trial. PARTICIPANTS: Thirty-six patients (36
      eyes) were randomized either to infrared SGLT (17 eyes) or to krypton TGLT (19
      eyes). METHODS: Complete ophthalmic examinations, including determination of
      visual acuity (VA) with Early Treatment Diabetic Retinopathy Study charts,
      optical coherence tomography (OCT), and fluorescein angiography, were performed
      at the time of the study entry and at 6-month intervals, with a planned follow-up
      of 24 months. MAIN OUTCOME MEASURES: Primary: decrease in mean foveal thickness
      (FT) on OCT. Secondary: changes of the total macular volume (TMV) over the follow
      up, proportion of eyes that gained at least 10 letters (approximately > or =2
      lines of VA gain) at the 12- and 24-month examinations, and timing of macular
      edema resolution. RESULTS: Changes in mean FT and TMV from the initial values
      were statistically significant for TGLT from the 6-month examination (P<0.001)
      and for SGLT from the 12-month examination (P<0.001). After 1 year, there was no
      difference in mean FT and TMV between the 2 groups. At the 12-month examination,
      10 patients of the SGLT group (59%) and 11 of the TGLT group (58%) gained at
      least 10 letters (2 lines) in VA. At the 24-month examination, this gain was
      achieved by 11 patients (65%) of the SGLT group and 11 (58%) of the TGLT group.
      Moreover, at the 24-month examination 59% and 26% gained 3 lines in the SGLT and
      TGLT groups, respectively. CONCLUSIONS: Resolution of macular edema and VA
      improvement are similar to those obtained with conventional TGLT, but SGLT is not
      associated with biomicroscopic and angiographic signs. A multicenter randomized
      clinical trial would be needed to ascertain the real efficacy and the most
      appropriate settings of SGLT for macular edema secondary to BRVO.

PMID- 16996598
TI  - Cost utility for penetrating keratoplasty in patients with poor binocular vision.
AB  - PURPOSE: Cost-utility and cost-effectiveness analyses are of increasing
      importance to clinicians and health policy experts. This study determines the
      costs in Germany and other countries in relation to gain of utility for patients
      with bilateral poor vision owing to corneal disease undergoing penetrating
      keratoplasty (PK) in 1 eye. DESIGN: A cost-utility analysis was performed using
      retrospective clinical data and high-level evidence-based data. PARTICIPANTS:
      Sixty patients (mean age, 46.3 years) with bilateral poor vision who underwent PK
      for corneal disease. METHODS: Visual acuity and utility values were obtained
      before and 1 year after PK and after suture removal. A 10-year graft survival
      rate of 80% was assumed. Expenses included costs for the corneal transplant and
      surgery, medication, and optical rehabilitation. A discount rate of 5% was
      applied for costs and quality-adjusted life years (QALYs). Cost-utility analysis
      encompassed a 10-year period after surgery. MAIN OUTCOME MEASURES: The number of
      QALYs was calculated for the study group undergoing PK. This was divided into the
      cost of the procedure to get the number of euros spent per QALY gained. RESULTS:
      Median binocular preoperative visual acuity was -log mean angle of resolution (
      logMAR) 0.91+/-0.53 (Snellen equivalent 20/160) yielding a utility value of 0.67.
      After suture removal and optical rehabilitation, binocular visual acuity
      increased to median -logMAR 0.36+/-0.36 (20/46) with a utility value of 0.79.
      Over the 10 years after surgery and considering graft survival and discounting, a
      cost utility of 9551 euros per QALY was gained (equivalent to US11,557 dollars).
      One-way sensitivity analysis yielded a range from 7706 euros to 12874 euros per
      QALY, highlighting the robustness of the model. CONCLUSIONS: Although an
      expensive procedure, PK is cost effective in patients with bilateral poor vision.

PMID- 16996597
TI  - The relation of ambulatory blood pressure and pulse rate to retinopathy in type 1
      diabetes mellitus: the renin-angiotensin system study.
AB  - PURPOSE: To examine the association of ambulatory blood pressure (ABP) and
      ambulatory pulse rate (APR) with diabetic retinopathy (DR) in persons with type 1
      diabetes in the Renin-Angiotensin System Study (RASS), a multicenter primary
      diabetic nephropathy (DN) prevention trial. DESIGN: Cross-sectional study.
      PARTICIPANTS: One hundred ninety-four normotensive RASS participants in 3 centers
      who are 16 years of age or older with type 1 diabetes mellitus (DM) of 2 to 20
      years' duration. METHODS: Ambulatory blood pressure and APR were monitored using
      standardized protocols. Patients were defined as nondippers if the night-to-day
      ratios for both systolic and diastolic blood pressures were >0.9. Diabetic
      retinopathy was determined by masked grading of 30 degrees color stereoscopic
      fundus photographs of 7 standard fields using the Early Treatment Diabetic
      Retinopathy Study severity scale. MAIN OUTCOME MEASURE: Severity of DR. RESULTS:
      No DR was present in 32%, mild nonproliferative DR (NPDR) was present in 55%, and
      moderate to severe NPDR or proliferative DR was present in 13% of the cohort.
      Neither 24-hour systolic ABP or diastolic ABP, daytime systolic or diastolic ABP,
      nor nighttime diastolic ABP were related to severity of DR. Statistically
      significant associations were found between nighttime systolic ABP and mean ABP
      and DR. Among those with no DR, 19% were nondippers; for those with mild NPDR,
      28% were nondippers; and for those with severe NPDR or proliferative DR, 36% were
      nondippers (P = 0.08). The ratio of nighttime to daytime APR, but not the 24-hour
      APR or daytime or nighttime APR, was related positively to the severity of DR. In
      multivariable analyses, only the nighttime systolic ABP was related to severity
      of DR (P<0.05). CONCLUSIONS: These data suggest that ABP, especially during the
      night, may provide a better measure than clinical BP regarding the relationship
      of BP to the severity of retinopathy in normotensive persons with type 1 DM
      without clinical DN.

PMID- 16996599
TI  - Effect of corneal thickness on dynamic contour, rebound, and goldmann tonometry.
AB  - PURPOSE: To identify correlations among intraocular pressure (IOP) measurements
      obtained using the rebound tonometer (RBT), the dynamic contour tonometer (DCT),
      and the Goldmann applanation tonometer (GAT). The effects of corneal thickness on
      the measures obtained using each of the 3 tonometers also were examined. DESIGN:
      Cross-sectional study. PARTICIPANTS: One hundred forty-six eyes of 90 patients
      with ocular hypertension or glaucoma. METHODS: Intraocular pressure measurements
      were obtained in all patients using RBT, DCT, and GAT. Central corneal thickness
      was determined by ultrasound pachymetry. Patients were divided randomly into 6
      groups to vary the order in which the tonometers were used. All IOP measurements
      were made by the same examiner, who was masked to the readings obtained. MAIN
      OUTCOME MEASURES: Intraocular pressure and central corneal thickness. RESULTS:
      There was good correlation between IOP readings obtained using the RBT and GAT (r
      = 0.864; P<0.0001), between DCT and GAT (r = 0.871; P<0.0001), and between RBT
      and DCT (r = 0.804; P<0.0001). Rebound tonometer and DCT readings consistently
      were higher than GAT measurements (RBT-GAT median difference, 1.4+/-2.7 mmHg; DCT
      GAT median difference, 4.4+/-2.6 mmHg). A Bland-Altman plot indicated that the
      95% limits of agreement between RBT and GAT were -4.3 to 6.4 mmHg (slope = 0.056;
      P = 0.218), those between DCT and GAT were -0.7 to 9.5 mmHg (slope = 0.016; P =
      0.717), and those between RBT and DCT were -3.1 to 9.8 mmHg (slope = -0.041; P =
      0.457). Using RBT, the point that best discriminated between patients with an IOP
      21 mmHg or less and more than 21 mmHg as determined by GAT was >23.3 mmHg
      (sensitivity, 66.7%; specificity, 92.1%); using DCT, this point was >22.7 mmHg
      (sensitivity, 95.6%; specificity, 71.3%). In terms of pachymetry, GAT and RBT
      behaved similarly. Using these instruments, differences of approximately 3 mmHg
      were detected between the groups of patients with the thinnest (<531 mum) and
      thickest (>565 mum) corneas, whereas a significantly lower difference (0.5 mmHg)
      was noted for the DCT. CONCLUSIONS: Measurements obtained both with the RBT and
      DCT show excellent correlation with those provided by applanation tonometry. Both
      tonometers tend to overestimate the IOP measured with the GAT, particularly the
      DCT. This last tonometer seems to be less affected by the corneal thickness.

PMID- 16996600
TI  - Photodynamic therapy with intravitreal triamcinolone in predominantly classic
      choroidal neovascularization: one-year results of a randomized study.
AB  - PURPOSE: To determine whether intravitreal triamcinolone acetonide (IVTA)
      improves the efficacy of photodynamic therapy (PDT) with verteporfin in
      predominantly classic subfoveal choroidal neovascularization (CNV) secondary to
      age-related macular degeneration (AMD). DESIGN: Prospective randomized study.
      PARTICIPANTS: Sixty-one patients with predominantly classic subfoveal CNV
      secondary to AMD. METHODS: Patients were randomized to receive PDT (n = 30) or
      PDT followed by approximately 11 mg IVTA (n = 31), with retreatment every 3
      months when leakage was documented by fluorescein angiography. At baseline and
      each follow-up visit, best-corrected visual acuity (VA) was measured with Early
      Treatment Diabetic Retinopathy Study charts by a certified examiner masked to the
      patient's treatment, lesion size on fluorescein angiography, and foveal thickness
      on optical coherence tomography. MAIN OUTCOME MEASURES: Mean change in VA
      (logarithm of the minimum angle of resolution [logMAR]) from baseline, percentage
      of patients losing fewer than 15 letters (3 lines) of VA, mean change in lesion
      size, mean change in foveal thickness, and retreatment rate. RESULTS: At the 12
      month follow-up, VA (mean logMAR change from baseline) was significantly better
      (P = 0.001) in the group of patients who received combined therapy. Seventy-four
      percent of patients treated with combined therapy compared with 61% treated with
      verteporfin alone lost fewer than 15 letters of VA (P = 0.78). Reduction in
      lesion size (P = 0.001) and in foveal thickness (P = 0.03) was significantly
      greater with combined therapy than with verteporfin. Retreatment rate was
      significantly lower (P = 0.04) in the combined therapy group. Triamcinolone
      related adverse events included glaucoma (25.8%) and cataract progression (32%).
      CONCLUSIONS: Combined PDT and IVTA therapy seemed to be more effective than PDT
      alone for managing predominantly classic subfoveal lesions secondary to AMD. The
      triamcinolone-related adverse events included glaucoma and cataract progression.

PMID- 16996601
TI  - Graft reepithelialization after penetrating keratoplasty using organ-cultured
      donor tissue.
AB  - OBJECTIVE: To analyze graft reepithelialization after penetrating keratoplasty
      using organ-cultured donor tissue. DESIGN: Retrospective observational cohort
      study. PARTICIPANTS: One thousand one hundred thirty-eight consecutive
      penetrating keratoplasties (1003 patients) performed between 1992 and 2004 were
      analyzed, and 1003 were included (1 graft per patient was included). METHODS:
      Slit-lamp examination after fluorescein staining. MAIN OUTCOME MEASURE: Graft
      reepithelialization time was recorded. RESULTS: The average graft
      reepithelialization time was 4.6+/-13.2 days (range, 1-210 days; median, 2.5
      days). Complete corneal epithelial healing was obtained in 1 day in 28.5% of
      patients, in 3 days in 65.8%, in 7 days in 93.6%, and in 14 days in 97.0%.
      Postoperative chronic epithelial defects occurred in 3.0% of patients. In
      univariate analysis, death-to-storage time, storage time, deswelling time,
      rejection risk, trephination size, suture method, use of dexamethasone ointment
      during surgery, use of sodium hyaluronate during surgery, and use of high
      postoperative steroid regimen significantly influenced the graft
      reepithelialization time (P<0.05). In multiple regression, only the rejection
      risk (beta = 0.07; P = 0.045), use of sodium hyaluronate at the end of surgery
      (beta = -0.17; P = 0.001), and steroid regimen (beta = 0.09; P = 0.022)
      significantly influenced the graft reepithelialization time. CONCLUSIONS: The use
      of sodium hyaluronate at the end of surgery to coat the ocular surface shortened
      graft reepithelialization time after penetrating keratoplasty using organ
      cultured donor tissue. Graft reepithelialization time was longer in high-risk
      recipients, and it increased with high dexamethasone eyedrops regimen.

PMID- 16996602
TI  - Trends of penetrating keratoplasty in the United States from 1980 to 2004.
AB  - PURPOSE: To examine the changing trends in penetrating keratoplasties (PKs)
      performed in the United States. DESIGN: Retrospective review. METHODS: Review of
      Eye Bank Association of America (EBAA) data on corneal tissue distribution in the
      United States from 1980 to 2004. Data analysis was retrospective. United States
      population census data were obtained and used for population-adjusted
      calculations. A series of Poisson regression models were calculated looking at
      the temporal trends over time. MAIN OUTCOME MEASURES: The estimated yearly
      percent change and P values were calculated using Poisson regression models.
      RESULTS: The total number of corneas distributed for PKs from EBAA member eye
      banks have steadily increased since 1980. In 1990, the international and domestic
      distribution data were separated. The total number of PKs performed from EBAA
      supplied tissue has continued to rise since 1990; however, the total number of
      PKs performed in the United States has steadily declined and when population
      adjusted rates are examined, the rate of decline is more dramatic. CONCLUSION:
      Although both absolute numbers and age-adjusted numbers of PKs have declined
      recently, the population-adjusted rates have dropped more significantly.

PMID- 16996603
TI  - Potential complications of ocular surgery in patients with coexistent keratoconus
      and Fuchs' endothelial dystrophy.
AB  - PURPOSE: To describe the potential complications of cataract and refractive
      surgery in patients with Fuchs' endothelial dystrophy (FED) and keratoconus.
      DESIGN: Retrospective case series. PARTICIPANTS: Eight patients with FED and
      keratoconus in a large university group practice. METHODS: We reviewed the
      clinical and topographic findings of 8 patients (15 eyes) with FED and
      keratoconus. Clinical examination, corneal topography, specular microscopy were
      done, and sequential central corneal thickness (CCT) was obtained. Follow-up
      ranged from 1 month to 6 years. MAIN OUTCOME MEASURES: Findings of keratoconus
      and FED in preoperative evaluation. RESULTS: Five patients had concomitant
      cataracts; 3 had refractive errors and sought surgical correction. Cataract
      surgery was performed on 3 of 5 patients (5 eyes). LASIK was performed on one eye
      of 3 patients. Of 5 eyes that underwent cataract extraction, 4 had blurry vision
      after surgery. The interval between the surgical procedure and onset of symptoms
      ranged from 1 month to 4 years. The causes of decreased vision after cataract
      surgery were corneal edema and/or corneal ectasia. The CCT readings ranged from
      426 to 824 microm. One of 4 symptomatic eyes underwent penetrating keratoplasty.
      The CCTs of 3 patients (6 eyes) who presented with refractive error ranged from
      507 to 565 microm. One eye had undergone an attempted LASIK procedure resulting
      in a lost cap. Corneal topography and specular microscopy showed the coexistence
      of keratoconus and FED, and the patients were advised against having LASIK
      surgery. CONCLUSIONS: Corneal thinning caused by keratoconus and concurrent
      increase in corneal thickness caused by FED may combine to normalize the corneal
      pachymetry readings; disease severity may be underestimated, which may lead to
      unexpected postoperative visual outcomes. Routine use of preoperative topography
      and specular microscopy may help to avert potential surgical complications.

PMID- 16996604
TI  - Positron emission tomography in the detection and staging of ocular adnexal
      lymphoproliferative disease.
AB  - PURPOSE: To evaluate the role of fluorine 18 deoxyglucose positron emission
      tomography (FDG PET) in the initial staging of ocular adnexal lymphoma (OAL).
      DESIGN: Retrospective nonrandomized case series. PARTICIPANTS: Eleven patients
      with OAL who underwent FDG PET at initial staging. METHODS: Retrospective review
      of all the clinical and imaging records, including computed tomography (CT) and
      FDG PET. MAIN OUTCOME MEASURES: The ability of PET studies to detect OAL and
      distant disease was compared with CT. RESULTS: Eleven patients with OAL who
      underwent FDG PET at initial staging were retrospectively reviewed having full
      access to their clinical and imaging data. Fluorine 18 deoxyglucose PET found
      distant disease in 5 of 6 lymphoma patients with systemic disease; 4 of these
      patients (66%) were upstaged, changing the clinical management. Orbital lesions
      were demonstrated in 3 of 11 patients, giving PET a sensitivity of 27% in the
      orbit and 83% systemically for detection of lymphoma. CONCLUSION: The ability of
      FDG PET to find systemic extranodal lymphomatous sites not detected with
      conventional imaging provides valuable information in OAL patients, which may
      result in important changes in staging and management. The technique does have
      limitations in detecting OAL compared with conventional imaging, possibly owing
      to background physiologic activity in the extraocular muscles in the orbit and
      the small volume of some orbital deposits.

PMID- 16996605
TI  - The International Classification of Retinoblastoma predicts chemoreduction
      success.
AB  - PURPOSE: To evaluate the reliability of the International Classification of
      Retinoblastoma (ICRB) for predicting treatment success with chemoreduction (CRD).
      DESIGN: Noncomparative interventional case series. PARTICIPANTS: Two hundred
      forty-nine consecutive eyes. METHODS: All eyes were treated with CRD and were
      classified according to the ICRB: group A included those eyes with retinoblastoma
      </=3 mm; group B included those eyes with retinoblastoma >3 mm, macular location,
      or minor subretinal fluid; group C included those eyes with retinoblastoma with
      localized seeds; group D included those eyes with retinoblastoma with diffuse
      seeds; group E included those eyes with massive retinoblastoma necessitating
      enucleation. The CRD regimen included vincristine, etoposide, and carboplatin for
      6 cycles plus local consolidation with thermotherapy or cryotherapy. MAIN OUTCOME
      MEASURE: Chemoreduction success, defined as avoidance of external beam
      radiotherapy or enucleation. RESULTS: Of the 249 eyes, 23 (9%) were in group A,
      96 (39%) were in group B, 21 (8%) were in group C, and 109 (44%) were in group D.
      In this series, group E eyes were managed with enucleation. Treatment success was
      achieved in 100% of group A, 93% of group B, 90% of group C, and 47% of group D
      eyes. CONCLUSIONS: The ICRB can be of assistance in predicting CRD success for
      retinoblastoma. Additional treatment methods are necessary to salvage more group
      D eyes.

PMID- 16996606
TI  - Comparing outcomes of enucleation and evisceration.
AB  - PURPOSE: To compare clinical outcomes of enucleation and evisceration by
      functional and aesthetic measures. DESIGN: Retrospective, nonrandomized,
      comparative analysis. PARTICIPANTS: Eighty-four patients who underwent
      enucleation or evisceration. METHODS: The medical records of the participants
      were retrospectively reviewed. Clinical photographs were graded by blinded
      observers for qualitative measures. MAIN OUTCOME MEASURES: Postoperative eyelid
      and motility measurements, as well as subjective grades of various aesthetic and
      functional outcomes. RESULTS: There is no statistically significant difference in
      the overall aesthetic outcome of enucleation and evisceration, although several
      specific comparisons were found to be significant. Implant motility score is
      higher in eviscerated eyes (5.58+/-2.08) than in enucleated eyes (4.35+/-1.69) (P
      = 0.05). Adduction of the implant is significantly less than abduction in
      eviscerated eyes (1.34 vs. 1.44; P = 0.02). Implant motility is greater than
      prosthesis motility. Both enucleation and evisceration result in enophthalmos and
      a sulcus defect. Seven of 32 patients (21.9%) who underwent enucleation
      experienced a complication, whereas only of 7 of 52 patients (13.5%) who
      underwent evisceration experienced a complication (P = 0.0002). The 2 most common
      complications were implant exposure and formation of a pyogenic granuloma.
      CONCLUSIONS: Although enucleation and evisceration produce aesthetically similar
      outcomes, eviscerated eyes have better implant motility and experience fewer
      complications. Both enucleation and evisceration result in enophthalmos, sulcus
      contour defects, and incomplete transfer of implant motility to the prosthesis.

PMID- 16996607
TI  - Multifocal choroiditis with panuveitis incidence of ocular complications and of
      loss of visual acuity.
AB  - PURPOSE: To estimate the incidences of ocular complications and vision loss in
      patients with multifocal choroiditis with panuveitis (MFCPU) and to describe the
      association between therapy and the incidences thereof. DESIGN: Retrospective
      cohort study. PARTICIPANTS: Sixty-six patients (122 eyes) with MFCPU evaluated
      from January 1984 through June 2005 at a single-center academic practice.
      METHODS: Demographic and clinical information on patients diagnosed with MFCPU
      was collected and entered into a computerized database for statistical analyses.
      MAIN OUTCOME MEASURES: Development of ocular complications, including choroidal
      neovascularization, epiretinal membrane, and cystoid macular edema (CME), and
      loss of visual acuity (VA) to 20/50 or worse and to 20/200 or worse. RESULTS:
      Among affected eyes of patients with MFCPU, frequencies of VAs of 20/50 or worse
      and of 20/200 or worse at presentation were 55% and 38%, respectively. Choroidal
      neovascularization was observed in 22% of affected eyes at presentation and was
      the leading cause of poor VA at presentation. The incidence rates of vision loss
      to 20/50 or worse and to 20/200 or worse were 0.19/eye-year (EY) and 0.12/EY in
      affected eyes and 0.07/person-year (PY) and 0.04/PY in better-seeing eyes.
      Choroidal neovascularization was the most common cause of incident vision loss,
      with approximately 45% of incident vision loss attributed to new-onset or
      recurrent choroidal neovascularization. Presence of epiretinal membrane and CME
      also was associated with the development of vision loss during follow-up. When
      taken in combination, the incidence of any posterior pole complication was
      0.13/EY in affected eyes. Use of immunosuppressive drug therapy (but not low-dose
      corticosteroid therapy) was associated with an 83% reduction in the risk of
      posterior pole complications (P = 0.004) and with a 92% reduction in the risk of
      20/200 or worse VA in affected eyes (P = 0.05). Of the 6 eyes with recurrent
      choroidal neovascularization, only one recurrence was observed, in a patient
      receiving immunosuppressive drug therapy. CONCLUSIONS: Treatment with
      immunosuppressive drugs may improve VA outcomes among patients with MFCPU by
      reducing the risk of sight-threatening posterior pole complications, including
      new-onset choroidal neovascularization and recurrent choroidal neovascularization
      among eyes with existing choroidal neovascularization.

PMID- 16996608
TI  - Angle-supported anterior chamber phakic intraocular lens explantation causes and
      outcome.
AB  - PURPOSE: To investigate the reasons for explantation of angle-supported phakic
      intraocular lenses (IOLs) as well as the outcome and safety of the explantation
      procedure. DESIGN: Consecutive retrospective series. PARTICIPANTS: One hundred
      eyes of 66 patients who underwent phakic angle-supported IOL explantation.
      INTERVENTION: Surgical explantation of anterior chamber angle-supported phakic
      IOLs. MAIN OUTCOME MEASURES: Visual acuity, refraction, and endothelial cell
      density. RESULTS: The main causes of explantation were cataract development (64
      cases [64%]), progressive endothelial cell loss (24 cases [24%]), and pupil
      ovalization (10 cases [10%]). According to the reason for phakic IOL explantation
      and the condition of the eye at time of explantation, 92 cases underwent
      bilensectomy (phakic IOL explantation followed by phacoemulsification of the
      crystalline lens), 2 cases underwent phakic IOL exchange, 4 cases underwent
      concomitant phakic IOL explantation and penetrating keratoplasty, and 2 cases
      underwent simple explantation of a phakic IOL. The mean time between phakic
      anterior chamber IOL implantation and explantation due to cataract was 10.04+/
      3.66 years (range, 2-14). The mean time between implantation and secondary
      intervention due to progressive endothelial cell loss was 8.97+/-2.21 years
      (range, 2-14), and most of these cases were related to a specific model of angle
      supported phakic IOL. CONCLUSION: Nuclear cataract was the most frequent reason
      for angle-supported phakic IOL explantation. Bilensectomy was effective and
      maintained the refractive benefits obtained with phakic IOL implantation. Few
      cases developed severe endothelial cell loss, most of them related to certain
      types of phakic IOLs.

PMID- 16996609
TI  - Comparison of the Moorfields classification using confocal scanning laser
      ophthalmoscopy and subjective optic disc classification in detecting glaucoma in
      blacks and whites.
AB  - OBJECTIVE: To compare the diagnostic accuracy of the Moorfields regression
      classification (MRC) and subjective optic disc evaluation in discriminating early
      to moderate glaucomatous from nonglaucomatous eyes. DESIGN: Cross-sectional
      observational study. PARTICIPANTS: Two hundred thirty-three patients with
      glaucoma and 216 normal subjects were included in the analysis. Racial groups
      were defined by self-description. METHODS: All subjects underwent confocal
      scanning laser ophthalmoscopy, stereophotography, and standard perimetry.
      Glaucoma was defined by visual field defect alone and confirmed with a second
      visual field test. Stereo photographs were graded as either normal or
      glaucomatous appearing in a masked fashion by 2 independent graders and
      adjudicated by a third grader in cases of disagreement. Mean disc area was
      compared between patients correctly and incorrectly diagnosed with either
      technique. MAIN OUTCOME MEASURES: Sensitivity and specificity of MRC and
      subjective evaluation of stereophotographs in the detection of glaucomatous
      visual field loss. RESULTS: With the MRC, the sensitivity and specificity were
      higher using the 95% cutoff than using the 99.9% cutoff. Classification based on
      subjective photo assessment had a greater agreement with the diagnosis of
      glaucoma than the MRC for blacks (MRC, sensitivity = 62.5%, specificity = 93.2%;
      Photo, sensitivity = 76.5%, specificity = 91.5%) and whites (MRC, sensitivity =
      67.0%, specificity = 92.2%; photo, sensitivity = 78.4%, specificity = 91.9%).
      Disc area was significantly larger in patients incorrectly diagnosed with the MRC
      (P = 0.0289). CONCLUSIONS: Subjective optic disc grading by glaucoma specialists
      outperformed the MRC with the HRT II in both black and white subjects. Both
      subjective and objective diagnostic methods were associated with similar
      sensitivity and specificity between racial groups. The MRC was more likely to
      provide an incorrect diagnosis in subjects with larger optic discs.

PMID- 16996610
TI  - Costs of refractive correction of distance vision impairment in the United
      States, 1999-2002.
AB  - OBJECTIVE: Correctable vision impairment caused by refractive error is common in
      the United States population. We estimated the direct costs of providing
      eyeglasses to all Americans (age> or =12) who need refractive correction to
      achieve good distance vision. DESIGN: Cross-sectional study of a nationally
      representative sample of United States citizens. PARTICIPANTS: Participants in
      the 1999-2002 National Health and Nutrition Examination Survey (NHANES), age > or
      = 12 years. The NHANES examines a nationally representative sample of the U.S.
      noninstitutionalized, civilian population. METHODS: Presenting and corrected
      visual acuity data were obtained using an autorefractor from 13,211 (93.0%) of
      the 14,203 participants who visited the NHANES Mobile Examination Center in 1999
      through 2002. Need for refractive correction was defined by current use of
      corrective lenses for distance vision, improvement to good visual acuity
      following autorefractor correction (using several cutpoints to define good visual
      acuity), or both. MAIN OUTCOME MEASURES: Estimates of direct cost for refractive
      correction (1 pair of complete eyeglasses and a refraction examination) were
      computed based on Centers for Medicare & Medicaid Services fee schedules for 2000
      and also based on expenditure data from the Medical Expenditure Panel Survey.
      RESULTS: The NHANES results indicate that >110 million Americans could or do
      achieve normal vision with refractive correction. The annual direct cost of
      correcting distance vision impairment is at least $3.8 billion. Of this amount,
      $780 million represents the annual cost of providing distance vision correction
      for persons > age 65. CONCLUSIONS: Correctable vision impairment due to
      refractive error is common in the United States population. These cost estimates
      provide useful information for public health endeavors aimed at provision of
      refractive correction to those who need it.

PMID- 16996611
TI  - Relationship of progression of visual field damage to postural changes in
      intraocular pressure in patients with normal-tension glaucoma.
AB  - PURPOSE: To evaluate whether postural changes of intraocular pressure (IOP) are
      associated with progression of visual field damage in patients with normal
      tension glaucoma (NTG). DESIGN: Prospective, noncomparative, nonrandomized study.
      PARTICIPANTS: Sixty eyes of 33 patients with NTG. METHODS: Intraocular pressure,
      blood pressure (BP), and pulse rate (PR) were measured in both sitting and supine
      positions. Visual fields were examined using Humphrey Field Analyzer (HFA; Zeiss
      Humphrey Instruments, Inc., San Leandro, CA). Changes in mean deviation (MD) per
      year (dB/year), that is, MD slope, were calculated by linear regression analysis
      of the HFA Statpac 2 program. MAIN OUTCOME MEASURES: The relationship between
      postural changes of IOP and MD slope was analyzed. The correlation between
      postural changes of IOP and cardiovascular parameters such as BP and PR also was
      analyzed. RESULTS: The IOP in the supine position was significantly higher than
      that in the sitting position (P<0.001, paired t test). There was no significant
      correlation between MD slope and sitting IOP (Pearson r = 0.172; P = 0.188), but
      a significant correlation was found between MD slope and supine IOP (r = -0.261;
      P = 0.043). The MD slope significantly correlated with IOP elevation caused by
      the postural change (r = -0.682; P<0.001). The systolic BP in the supine position
      correlated with postural changes of IOP (r = 0.364; P = 0.004), but other
      cardiovascular parameters did not correlate with IOP parameters. CONCLUSIONS: The
      progression of visual field damage in NTG is associated with IOP in the supine
      position and the magnitude of IOP elevation accompanying postural changes. These
      results suggest that deterioration in NTG may occur when patients are lying flat
      during sleep.

PMID- 16996612
TI  - Atropine for the treatment of childhood myopia.
AB  - PURPOSE: To evaluate the efficacy and safety of topical atropine, a nonselective
      muscarinic antagonist, in slowing the progression of myopia and ocular axial
      elongation in Asian children. DESIGN: Parallel-group, placebo-controlled,
      randomized, double-masked study. PARTICIPANTS: Four hundred children aged 6 to 12
      years with refractive error of spherical equivalent -1.00 to -6.00 diopters (D)
      and astigmatism of -1.50 D or less. INTERVENTION: Participants were assigned with
      equal probability to receive either 1% atropine or vehicle eye drops once nightly
      for 2 years. Only 1 eye of each subject was chosen through randomization for
      treatment. MAIN OUTCOME MEASURES: The main efficacy outcome measures were change
      in spherical equivalent refraction as measured by cycloplegic autorefraction and
      change in ocular axial length as measured by ultrasonography. The primary safety
      outcome measure was the occurrence of adverse events. RESULTS: Three hundred
      forty-six (86.5%) children completed the 2-year study. After 2 years, the mean
      progression of myopia and of axial elongation in the placebo-treated control eyes
      was -1.20+/-0.69 D and 0.38+/-0.38 mm, respectively. In the atropine-treated
      eyes, myopia progression was only -0.28+/-0.92 D, whereas the axial length
      remained essentially unchanged compared with baseline (-0.02+/-0.35 mm). The
      differences in myopia progression and axial elongation between the 2 groups were 
      0.92 D (95% confidence interval, -1.10 to -0.77 D; P<0.001) and 0.40 mm (95%
      confidence interval, 0.35-0.45 mm; P<0.001), respectively. No serious adverse
      events related to atropine were reported. CONCLUSIONS: Topical atropine was well
      tolerated and effective in slowing the progression of low and moderate myopia and
      ocular axial elongation in Asian children.

PMID- 16996613
TI  - The lower eyelid retractor consists of definite double layers.
AB  - PURPOSE: To examine whether the lower eyelid retractor consists of a single layer
      or multiple layers. DESIGN: Retrospective clinical case series and dissectional
      study. PARTICIPANTS: Fifty-one lower eyelid retractors (31 right, 20 left) of 44
      patients (ages, 63-95 years) during entropion surgeries and 10 lower eyelids (5
      right, 5 left) of 5 Oriental cadavers (73-91 years old at death) were observed
      macroscopically. Specimens from 20 postmortem lower eyelids of 12 Orientals (11
      right, 9 left; 66-96 years old at death) were used for microscopic observations.
      METHODS: Macroscopically, we bluntly or, in parts, sharply dissected lower eyelid
      retractors into 2 layers during entropion surgeries. Cadaveric lower eyelids also
      were used to investigate relationships between the lower eyelid retractor and the
      Lockwood ligament. Cadaveric lower eyelids with sagittal full-thickness sections
      of the central part were examined microscopically using Masson trichrome
      staining. MAIN OUTCOME MEASURES: Anatomical findings in the lower eyelid
      retractor. RESULTS: Lower eyelid retractors easily were detached into 2 layers.
      Macroscopically, the anterior layer was defined as a coarse tissue continuing
      from the Lockwood ligament, which joined with the lower orbital septum, and
      constituted the lower conjoined fascia. The posterior layer appeared to be a
      dense fibrous sheet with a lustrous surface. Microscopically, the lower eyelid
      retractor consisted of a definite double layer. The anterior layer, a coarse
      fibrous tissue, consisted of the suborbicularis fascial layer, orbital septum,
      and superficial part of the capsulopalpebral fascia, which continued to the
      anterior lamellae of the lower eyelids. The posterior layer consisted of dense
      fibers of the capsulopalpebral fascia with smooth muscle continuing to the
      tarsus. CONCLUSIONS: The lower eyelid retractor consists of a definite double
      layer. The posterior dense layer containing smooth muscle is the main tractional
      component of the lower eyelid retractor.

PMID- 16996614
TI  - Primary treatment of acute retinal necrosis with oral antiviral therapy.
AB  - PURPOSE: To explore the possibility of oral antiviral therapy in lieu of
      intravenous acyclovir for treating acute retinal necrosis (ARN), a necrotizing
      retinopathy caused by herpes simplex virus type 1 or 2 or by varicella zoster
      virus. DESIGN: Retrospective, interventional, small case series. PARTICIPANTS:
      Four patients (6 eyes). METHODS: Patients were treated with oral antiviral
      therapy. Medications included valacyclovir (1 g 3 times daily), oral famciclovir
      (500 mg 3 times daily), and topical and oral corticosteroids. MAIN OUTCOME
      MEASURES: Improvement of symptoms, including photophobia, blurred vision, ocular
      discomfort, and floaters; increase in visual acuity; and resolution of vitreitis,
      retinitis, and retinal vasculitis, where present. RESULTS: Symptoms and visual
      acuity improved within 2 weeks to 1 month in 3 of 4 patients (75%) treated with
      oral antiviral medication. One patient required surgical treatment for
      asymptomatic retinal detachment after 3 weeks of treatment; retinal detachment in
      the fellow eye was repaired 2 months later. Duration of antiviral therapy ranged
      from 5 weeks to 3 months. CONCLUSIONS: For 4 patients with relatively indolent
      cases of ARN, oral antiviral therapy alone was effective in eliminating signs and
      symptoms of the disease. In particular, oral valacyclovir and famciclovir
      appeared to be effective, although further study is necessary to determine
      whether these drugs are as effective as intravenous acyclovir for initial
      treatment of ARN.

PMID- 16996615
TI  - Differential effectiveness of etanercept and infliximab in the treatment of
      ocular inflammation.
AB  - PURPOSE: Anti-tumor necrosis factor alpha (anti-TNF-alpha) agents are being used
      increasingly in refractory inflammatory eye diseases. We reviewed our patients on
      etanercept and infliximab to determine whether these medications are equally
      efficacious in controlling ocular inflammation. DESIGN: Exploratory retrospective
      analysis. PARTICIPANTS: Patients with ocular inflammatory disease on an anti-TNF
      alpha agent (etanercept, infliximab). METHODS: Case records of 22 patients
      treated with anti-TNF-alpha therapy were reviewed for demographic information,
      ocular and systemic diagnosis, duration and dose of anti-TNF-alpha treatment,
      concomitant ocular and systemic immunosuppressive medications, and treatment
      response. MAIN OUTCOME MEASURES: Uveitis recurrence rate, initial treatment
      response, treatment response, and medication use at 6 months, 1 year, and last
      visit. RESULTS: Patients treated with infliximab had a significant decrease in
      uveitis recurrences after starting therapy compared with those treated with
      etanercept (59% vs. 0%, P = 0.004). One year after treatment initiation and at
      final visit, more infliximab-treated patients had an improvement in their ocular
      inflammation (100% vs. 33%, P = 0.002, and 94% vs. 0%, P<0.001, respectively) and
      a decreased requirement for topical prednisolone acetate 1% (94% vs. 33%, P =
      0.009, and 89% vs. 29%, P = 0.007, respectively) compared with those treated with
      etanercept. No significant differences in the use of oral corticosteroids and
      immunosuppressive agents were noted between the 2 groups at 6 months, 1 year, and
      final visit. CONCLUSIONS: Infliximab was more effective than etanercept in the
      treatment of recalcitrant uveitis and decreased the use of topical steroids.

PMID- 16996616
TI  - A new multi-electrode array design for chronic neural recording, with independent
      and automatic hydraulic positioning.
AB  - We report on a new microdrive design, which enables the construction of multi
      electrode arrays capable of chronically recording the multi-unit neural activity
      of waking animals. Our principal motivation for inventing this device was to
      simplify the task of positioning electrodes, which consumes a considerable amount
      of time and requires a high level of skill. With the new microdrives, each
      electrode is independently and automatically driven into place. A hydraulic drive
      system is adopted to reduce the size, weight, and cost of the structure. The
      hydraulic fluid is also used as a part of the electrical circuit, and facilitates
      the wiring of the electrodes. A routing system has been attached to reduce the
      number of tube connections. The microdrive is cylindrical, has a diameter of 23.5
      mm, a height of 37 mm, and a weight of 15 g. It allows for up to 22 electrodes,
      which are arranged on a 0.35 mm grid. Each electrode can be positioned at any
      depth up to approximately 4mm. The microdrive was evaluated under acute and
      chronic recording experiments, and is shown to be capable of automatically
      positioning each electrode and successfully recording the neural signals of
      waking rats.

PMID- 16996617
TI  - Reduced anticardiolipin antibodies in first episode and chronic schizophrenia.
AB  - The objective of this study was to measure anticardiolipin antibodies (aCL) in
      major psychiatric diseases. In Experiment 1, 96 subjects were evaluated: 20 first
      episode schizophrenia patients, [SCZ1] 20 chronic schizophrenia patients in acute
      exacerbation [SCZ2], l9 bipolar patients, 20 schizoeffective patients and 17
      healthy age matched controls. In Experiment 2, 97 subjects were studied: 20 first
      episode schizophrenia patients [SCZ1], 60 chronic schizophrenia patients in acute
      exacerbation [SCZ2] and 17 healthy matched controls. Diagnosis was performed
      according to DSM-IV. Serum samples were tested for aCL in parallel by enzyme
      linked immunosorbent assay in the presence of bovine serum. Five positive control
      samples with high levels of aCL were run in parallel. Background binding to wells
      uncoated with cardiolipin (CL) was also measured. In Experiment 1, aCL levels
      were similar in the control, bipolar and schizoeffective groups. In contrast, aCL
      levels in the SCZ1 and SCZ2 groups were significantly lower than in controls. In
      Experiment 2, Significantly lower levels of aCL antibodies were found in all
      schizophrenic patients versus controls. Interestingly, background levels in both
      experiments were higher in the schizophrenic groups than in controls. Serum aCL
      levels are lower in schizophrenic patients, and especially in first episode
      cases, than in controls. One possible explanation for the lower levels of aCL in
      schizophrenic patients is the consumption of these antibodies in the acute phase
      and exacerbation of the disease. The higher background levels in schizophrenic
      patients may indicate a high level of antibodies to some serum component in
      schizophrenic patients that is still unclear and needs further elucidation.

PMID- 16996618
TI  - Comparison of two endoscopically assisted procedures in primary surgical
      treatment of congenital nasolacrimal duct obstruction in children older than 3
      years: balloon dilatation and bicanalicular silicone tube intubation.
AB  - OBJECTIVES: To determine the success of two transnasally endoscopic assisted
      procedures as balloon dilatation and bicanalicular silicone tube intubation for
      the primary surgical treatment of congenital nasolacrimal duct obstruction in
      children older than 3 years. STUDY DESIGN: Prospective randomized clinical trial.
      METHODS: An interventional case series of consecutive primary endoscopic assisted
      balloon dilatation (BD) and bicanalicular silicone tube intubation (STI) for
      congenital nasolacrimal duct obstruction in children older than 3 years was
      reviewed. BD was performed in 20 eyes of 17 patients and STI was performed 24
      eyes of 20 patients. Clinical success was defined as a complete remission of
      epiphora at the end of follow-up period of 12 months and a continuation of the
      remission at least for 4 months. RESULTS: Eighteen out of 20 eyes (90%)
      nasolacrimal ducts responded to BD whereas the rate was 15 out of 24 eyes (62.5%)
      in STI group. No significant complications occured in BD group while the
      complication rate in STI group was 8 out of 24 eyes (33.3%). chi(2)-Statistical
      analysis showed significantly better results for BD in clinical success and
      complication rates than those of STI. CONCLUSIONS: BD should be the first choice
      therapy instead of invasive approaches with high rate of complications and lower
      success rates such as silicone intubation, in patients who are older than 3
      years.

PMID- 16996619
TI  - Internal auditory canal stenosis in congenital sensorineural hearing loss.
AB  - OBJECTIVE: Sensorineural hearing loss (SNHL) due to internal auditory canal (IAC)
      stenosis with hypoplasia of the cochleovestibular nerve is a rare disorder. The
      diagnosis of the IAC stenosis requires both high resolution computed tomography
      scan (HRCT) and magnetic resonance imaging (MRI). METHODS: A retrospective review
      over 6 years in an academic tertiary referral center was performed. RESULTS: Six
      patients with congenital SNHL were diagnosed with congenital IAC stenosis. Four
      had unilateral and two had bilateral IAC stenosis after imaging. MRI showed
      hypoplastic vestibulocochlear nerve in all cases. CONCLUSIONS: This paper
      highlights the importance of imaging in diagnosing IAC stenosis and detecting the
      presence of cochleovestibular nerve in cases of congenital SNHL.

PMID- 16996620
TI  - Targeting tumor-associated carbonic anhydrase IX in cancer therapy.
AB  - Carbonic anhydrase isoform IX (CA IX) is highly overexpressed in many types of
      cancer. Its expression, which is regulated by the HIF-1 transcription factor, is
      strongly induced by hypoxia and correlates with a poor response to classical
      chemo- and radiotherapies. CA IX contributes to acidification of the tumor
      environment by efficiently catalyzing the hydration of carbon dioxide to
      bicarbonate and protons, thereby leading to acquisition of metastatic phenotypes
      and chemoresistance to weakly basic anticancer drugs. Inhibition of this
      enzymatic activity by specific inhibitors, such as the sulfonamide indisulam,
      reverts these processes, establishing a clear-cut role for CA IX in
      tumorigenesis. Thus, selective CA IX inhibitors could prove useful for
      elucidating the role of CA IX in hypoxic cancers, for controlling the pH
      imbalance in tumor cells and for developing diagnostic or therapeutic
      applications for tumor management. Indeed, fluorescent inhibitors and membrane
      impermeant sulfonamides have recently been used as proof-of-concept tools,
      demonstrating that CA IX is an interesting target for anticancer drug
      development.

PMID- 16996621
TI  - The MATE proteins as fundamental transporters of metabolic and xenobiotic organic
      cations.
AB  - Multidrug and toxic compound extrusion (MATE) proteins, comprising the most
      recently designated family of multidrug transporter proteins, are widely
      distributed in all kingdoms of living organisms, although their function is far
      from understood. The bacterial MATE-type transporters that have been
      characterized function as exporters of cationic drugs, such as norfloxacin and
      ethidium, through H(+) or Na(+) exchange. Plant MATE-type transporters are
      involved in the detoxification of secondary metabolites, including alkaloids.
      Mammalian MATE-type transporters are responsible for the final step in the
      excretion of metabolic waste and xenobiotic organic cations in the kidney and
      liver through electroneutral exchange of H(+). Thus, we propose that members of
      the MATE family are organic cation exporters that excrete metabolic or xenobiotic
      organic cations from the body.

PMID- 16996623
TI  - Demanding pups improve maternal behavioral impairments in sensitized and
      haloperidol-treated lactating female rats.
AB  - The impairments in the maternal behavior of ovariectomized sensitized females,
      relative to lactating dams, resemble those deficits found in lactating females
      after treatment with the D1/D2 DA receptor antagonist haloperidol, which
      interferes with maternal motivation. Therefore, it could be speculated that these
      behavioral deficits found in sensitized females and haloperidol-treated dams are
      due to a reduced motivation to interact with pups. In support of this hypothesis,
      we have found that both sensitized and haloperidol-treated lactating females
      exhibited remarkably similar impairments in the expression of all active maternal
      behaviors relative to lactating dams. Furthermore, these deficits were overridden
      when they were allowed to interact with 12h-isolated pups (demanding pups).
      Interestingly, lactating dams also improved their maternal behavior in the
      presence of demanding pups, and clearly chose demanding more than non-demanding
      pups in a preference paradigm. These data support the idea that the behavioral
      deficits of sensitized and haloperidol-treated lactating females are due to a
      reduced behavioral activation in response to the incentive cues from pups
      compared to lactating dams, and not because of a motor inability to express
      maternal behavior. These findings ultimately suggest that pups modulate the
      activity of DA system involved in the regulation of maternal behavior.

PMID- 16996624
TI  - Copper toxicity across salinities from freshwater to seawater in the euryhaline
      fish Fundulus heteroclitus: is copper an ionoregulatory toxicant in high
      salinities?
AB  - Two waterborne Cu exposures were performed to investigate if Cu is an
      ionoregulatory toxicant at all salinities in the killifish, Fundulus
      heteroclitus. A 30-day flow through exposure in 0 (FW), 5, 11, 22, and 28 ppt
      (SW) and three [Cu]'s (nominal 0, 30, and 150 microg Cu L(-1)) revealed no
      apparent Cu induced mortality at the intermediate salinities and high mortality
      in FW and SW. Fish were sampled at 4, 12, and 30 days after the start of the
      exposure and both Na+/K+ adenosine triphosphatase (Na+/K+ ATPase) and carbonic
      anhydrase (CA) activity in the gill and intestine as well as whole body [Na+],
      and [Cl-] were measured. At the high [Cu] a reduction of whole body [Na+] after 4
      days of exposure in FW was the only physiological parameter influenced. A second
      static 24h Cu exposure was performed in FW, 5, 13, and 29 ppt (SW) and two [Cu]'s
      (nominal 0 and 110 microg Cu L(-1)). In addition to the parameters listed above,
      ammonia flux was measured at all salinities and Na+ flux was measured in FW fish.
      Cu affected ionoregulation in FW where decreased Na+ uptake associated with
      inhibition of Na+/K+ ATPase led to decreased whole body [Na+] after 24h. The only
      affected parameter in SW was net ammonia excretion suggesting that Cu is not an
      ionoregulatory toxicant in SW at the concentrations employed. We propose that
      physiology rather than chemistry explain much of the variation in Cu toxicity
      seen across salinities.

PMID- 16996622
TI  - Transporters involved in resistance to antimalarial drugs.
AB  - The ability to treat and control Plasmodium falciparum infection through
      chemotherapy has been compromised by the advent and spread of resistance to
      antimalarial drugs. Research in this area has identified the P. falciparum
      chloroquine resistance transporter (PfCRT) and the multidrug resistance-1
      (PfMDR1) transporter as key determinants of decreased in vitro susceptibility to
      several principal antimalarial drugs. Transfection-based in vitro studies are
      consistent with clinical findings of an association between mutations in the
      pfcrt gene and failure of chloroquine treatment, and between amplification of the
      pfmdr1 gene and failure of mefloquine treatment. Many countries are now switching
      to artemisinin-based combination therapies. These incorporate partner drugs of
      which some have an in vitro efficacy that can be modulated by changes in pfcrt or
      pfmdr1. Here, we summarize investigations of these and other recently identified
      P. falciparum transporters in the context of antimalarial mode of action and
      mechanisms of resistance.

PMID- 16996625
TI  - Determination of the androgenic potency of whole effluents using mosquitofish and
      trout bioassays.
AB  - This study combined bioassay-derived and direct chemical analysis of steroidal
      compounds in pulp and paper and municipal sewage effluent in order to determine
      the cause of masculinization of female mosquitofish. The bioassays used in this
      study consisted of androgen and estrogen receptor binding, and aromatase
      inhibition using tissues from rainbow trout. This study observed no
      masculinization of female mosquitofish from a pulp and paper mill effluent that
      was previously observed to cause this effect. Mosquitofish sampled from the
      receiving environment of the same mill verified that masculinization was not
      occurring in the wild. The municipal sewage effluent also had no masculinizing
      effect. In vitro bioassays indicated significant sources of both androgens and
      estrogens in the effluents tested with sewage effluent having both the highest
      estradiol (41 ng/L) and testosterone (182 ng/L) equivalent concentration. These
      results could not be attributed to any particular compounds measured in the
      effluents. Two compounds implicated in the masculinization of mosquitofish by
      pulp and paper effluent, androstenedione and androstadienedione required
      relatively large (10-100 microg/L) waterborne concentrations to elicit a
      masculinizing effect and neither of these compounds are likely to occur at levels
      this high in the natural environment. The potent aromatase inhibitor, 4
      hydroxyandrostenedione also did not cause masculinization at 100 microg/L
      indicating that masculinization did not occur through this mechanism. The
      mammalian anti-androgen, cyproterone acetate was only partially effective in
      mosquitofish and reduced the severity of masculinization in the presence of
      methyl testosterone. While neither effluent masculinized mosquitofish, there was
      a significant reduction of in vitro ovarian steroid production with the most
      severe effects observed with the sewage effluent. Overall, this study found the
      disappearance of a masculinizing effect that had been previously observed;
      concluded that based on 21 days aqueous exposures androstenedione and
      androstadienedione are not likely candidates for mosquitofish masculinization,
      and showed that masculinization and in vitro steroid production are unrelated
      biological endpoints.

PMID- 16996626
TI  - Heterotypic complex formation between subunits of microtubule-associated proteins
      1A and 1B is due to interaction of conserved domains.
AB  - The microtubule-associated proteins MAP1A and MAP1B are related but distinct
      multi-subunit protein complexes that consist of heavy and light chains. The
      predominant forms of these complexes are homotypic, i.e. they consist of a MAP1A
      heavy chain associated with MAP1A light chains or a MAP1B heavy chain associated
      with MAP1B light chains, respectively. In addition, MAP1A and MAP1B can exchange
      subunits and form heterotypic complexes consisting of a MAP1A heavy chain
      associated with MAP1B light chains which might play a role in a transition period
      of neuronal differentiation. Here we extend previous findings by confirming that
      heterotypic MAP1B heavy chain-MAP1A light chain complexes also exist in the
      developing murine brain. We show that these complexes form through interaction of
      homologous domains conserved in heavy and light chains of MAP1A and MAP1B.
      Likewise, conserved domains of the MAP1A and MAP1B light chains account for
      formation of light chain heterodimers. By yeast 2-hybrid analysis we located the
      light chain binding domain on the heavy chain to amino acids 211-508, thereby
      defining a new functional subdomain.

PMID- 16996627
TI  - The import receptor Pex7p and the PTS2 targeting sequence.
AB  - This chapter concerns one branch of the peroxisome import pathway for newly
      synthesized peroxisomal proteins, specifically the branch for matrix proteins
      that contain a peroxisome targeting sequence type 2 (PTS2). The structure and
      utilization of the PTS2 are discussed, as well as the properties of the receptor,
      Pex7p, which recognizes the PTS2 sequence and conveys these proteins to the
      common translocation machinery in the peroxisome membrane. We also describe the
      recent evidence that this receptor recycles into the peroxisome matrix and back
      out to the cytosol in the course of its function. Pex7p is assisted in its
      functioning by several species-specific auxiliary proteins that are described in
      the following chapter.

PMID- 16996628
TI  - Brain oscillations differentiate the picture of one's own grandmother.
AB  - The present report introduces, as a first study, the concept and methods of
      oscillatory brain dynamics to analyze well-known (familiar) and unfamiliar face
      processing in the 800 ms following a face presentation. We analyzed event-related
      oscillations in young, healthy subjects (N=26) by using three types of
      stimulation: (1) a simple light signal, (2) the picture of the face of an
      anonymous elderly lady and (3) the picture of the subjects' own grandmother. We
      found a number of significant peak to peak amplitude measures in all frequency
      bands in the time period of 0-500 ms, allowing a differentiation between
      perception of the subjects' own grandmother, the unknown elderly face and the
      light stimulation. The results showed increased event-related oscillatory
      responses elicited by the unknown face compared to the known grandmother a) in
      the theta responses (4-8 Hz) at T(6) (46%), b) in the gamma (28-48 Hz) responses
      at C(z) (22%) and C(3) (38%) and c) in the beta responses at F(4) (46%), C(z)
      (47%) and P(3) (105%). In contrast, the subjects' own grandmother elicited 20%
      increased fast theta (6-8 Hz) oscillations at F(4) compared to the unknown face.
      Delta responses dissociated face from simple light processing, as reflected in
      the observation of approx. 50% higher amplitudes at the occipital compared to the
      frontal locations during face perception. We conclude that the described multiple
      brain oscillations clearly differentiate the known and unknown faces with varied
      degrees of selective-responsiveness in a short time window between 0 and 800 ms.
      Furthermore, the results are in conceptual accordance with the "selectively
      distributed processing" hypothesis.

PMID- 16996629
TI  - Altered nucleotide sugar metabolism in Streptococcus thermophilus interferes with
      nitrogen metabolism.
AB  - Exopolysaccharide (EPS)-producing Streptococcus thermophilus strains have
      attracted interest recently, since the EPSs act as natural viscosifiers and
      texture enhancers of fermented foods. We have previously reported that the low
      level of EPS production by S. thermophilus LY03 could be improved by altering the
      activities of enzymes in the central carbon metabolism involved in the nucleotide
      sugar metabolism. In this study, we observed a reduced growth in milk for the
      strains with increased UDP-glucose pyrophosphorylase (GalU) activity together
      with either enhanced phosphoglucomutase activity, and/or enhanced activity of the
      Leloir enzymes. Rapid growth of these mutants in milk could be restored by the
      addition of four specific amino acids, i.e. Glu, His, Met, and Val. This amino
      acid requirement was confirmed in a defined medium. Furthermore, the 31P NMR
      spectra showed higher levels of the GalU reactants pyrophosphate (PPi) and UDP
      glucose in the engineered strain, TMB 6013, compared to the parent strain, LY03.
      These products plus Glu and the GalU reactant UTP are known to be involved in the
      nitrogen regulatory system in many bacteria. Thus, these results suggest that the
      reaction catalyzed by GalU is connected to the nitrogen demand of these
      engineered strains.

PMID- 16996630
TI  - Seasonal and tissue distribution of Laribacter hongkongensis, a novel bacterium
      associated with gastroenteritis, in retail freshwater fish in Hong Kong.
AB  - Laribacter hongkongensis, a recently discovered bacterium associated with
      community-acquired gastroenteritis, has been found in the intestines of
      freshwater fish. To better understand the epidemiology and ecology of the
      bacterium, we carried out a surveillance study to investigate possible seasonal
      variation in the recovery of L. hongkongensis and its distribution in various
      organs in retail freshwater fish in Hong Kong. Forty whole freshwater fish of two
      species (20 grass carps and 20 bighead carps), and intestines from 120 grass
      carps were sampled during a one-year period. L. hongkongensis was isolated from
      11 (55%) of the 20 grass carps and 6 (30%) of the 20 bighead carps; and the
      intestines of 49 (41%) of 120 grass carps. Seasonal variation in the recovery of
      L. hongkongensis from both whole fish and intestines was observed, with higher
      isolation rates in spring and summer than in fall and winter. There was also
      positive correlation between temperature and the isolation rates. When L.
      hongkongensis was cultured in vitro at different temperatures, shorter lag time
      and higher growth rate were observed at higher temperatures, with 37 degrees C
      being optimal among the tested temperatures. L. hongkongensis was commonly found
      in the gills, stomachs and intestines in both grass carps and bighead carps, and
      on the skin surface of one fish, but not in other organs. Proper handling of
      freshwater fish for cooking, especially the gills and gut, is recommended to
      prevent acquisition of L. hongkongensis, and other freshwater fish related
      infections.

PMID- 16996631
TI  - Plasmid exchanges among members of the Bacillus cereus group in foodstuffs.
AB  - The Bacillus cereus sensu lato group is genetically very close and possesses a
      remarkable plasmid gene pool that encodes a variety of functions such as
      virulence and self-transfer capabilities. The potential for horizontal transfer
      among the various subspecies of this group, which includes the human
      opportunistic pathogens B. cereus sensu stricto and B. anthracis as well as the
      biopesticide B. thuringiensis, has led to growing concerns regarding food safety
      and public health. In this study, the conjugative behaviour of B. thuringiensis
      strains was compared in LB medium, milk and rice pudding using the pXO16 and
      pAW63 conjugative systems, as well as the mobilisable plasmid pC194, in bi- and
      triparental matings. Conjugation and mobilisation of these plasmids were shown to
      occur at significant levels in both food products, attaining the highest transfer
      frequencies in milk, with an approximately ten-fold increase in conjugative
      transfer in this growth medium as compared to liquid LB. Furthermore, the ability
      of an emetic strain of B. cereus to function as either plasmid donor or recipient
      partner in heterologous biparental matings with B. thuringiensis was demonstrated
      in these food matrices.

PMID- 16996632
TI  - A preliminary study of caffeine degradation by Pseudomonas sp. GSC 1182.
AB  - Several microorganisms isolated from soil were tested for their ability to
      utilize caffeine as the sole carbon and nitrogen source. The isolate identified
      as Pseudomonas sp. GSC 1182 showed 80% degradation of caffeine in 48 h when
      caffeine was used as the sole carbon and nitrogen source. In the presence of
      sucrose (5 g/l), 100% degradation of caffeine was achieved within 36-40 h. The
      degradation rate was also found to increase when fructose, lactose and galactose
      were used as carbon source. The isolate showed decreased level (<10%) of caffeine
      degradation in the presence of glucose. At an initial pH of 6.0, the complete
      degradation of caffeine was attained in 24 h. The addition of urea and ammonium
      sulfate as external nitrogen source decreased the caffeine degradation to 35% and
      70% respectively.

PMID- 16996633
TI  - Phenylalanine dehydrogenase mutants: efficient biocatalysts for synthesis of non
      natural phenylalanine derivatives.
AB  - Wild-type phenylalanine dehydrogenase from Bacillus sphaericus, and three mutants
      N145A, N145V and N145L, are used with a coenzyme recycling system to synthesise L
      phenylalanine and three non-natural amino acids (p-F-phenylalanine, p-MeO
      phenylalanine and p-CF(3)-phenylalanine) on a millimole scale. A range of
      reaction conditions are investigated. The kinetic parameters of WT PheDH and
      N145A towards p-CF(3)-phenylpyruvate are compared, emphasising the value of
      protein engineering in creating improved biocatalysts.

PMID- 16996634
TI  - Impact of a polyomavirus (BKV) infection on mRNA expression in human endothelial
      cells.
AB  - Polyomavirus BK-associated nephropathy (PVAN) is an emerging cause of early renal
      transplant failure. In order to learn more about the cellular response to BK
      virus, microarrays were used to study its effect on mRNA expression in human
      endothelial cells. The oligo-based, 35k arrays used cover the predicted 25,000
      human protein-expressing genes, and distinguish between a number of alternatively
      spliced mRNAs. Four parallel experiments were performed for each of two time
      points (24 and 40 h) during the first round of the 48 h viral replicative cycle.
      Immunoperoxidase staining demonstrated that the pulse exposure to virus caused
      infection in at least 75% of the cells. At 24 h, 55 genes were more than doubly
      up-regulated and 249 genes were similarly down-regulated; at 40 h, the numbers
      were 242 and 104, respectively. Gene ontology analyses suggested that
      immune/defence response genes were selectively down-regulated. Genes involved in
      cell division and DNA replication tended to be up-regulated, which may reflect an
      attempt on behalf of the virus to promote viral replication. Genes associated
      with PVAN were not induced, suggesting that these genes are not required for
      viral replication, but rather reflect circumstances specific for the disease.
      Only a few immuno-related genes were turned on, including the interferon response
      genes G1P2 and IFIT3. However, some of the up-regulated genes of unknown function
      may be involved in viral defence.

PMID- 16996635
TI  - Acid-cleavable polymeric core-shell particles for delivery of hydrophobic drugs.
AB  - Here we describe the combined use of acid-labile microgel approach and RAFT
      mediated seeded dispersion polymerization technique to prepare an acid-cleavable
      core-shell like polymeric colloidal system for the delivery of hydrophobic drugs
      at slightly acidic sites. A new bisacrylate acetal crosslinker was copolymerized
      with n-butyl acrylate (BA) in the presence of a RAFT agent using a dispersion
      polymerization technique, which yielded crosslinked spherical particles with the
      size ranging between 150 and 500 nm. The particles were cleaved in a pH-dependent
      manner similar to the acid-labile hydrolysis behaviour of the crosslinker. In
      order to mask the hydrophobic surface of the particles, polyethylene glycol
      acrylate (PEG-A) was grafted onto poly(BA) seed particles via the RAFT agent
      groups on the particle surface. The acidic-site selective delivery potential of
      the poly(BA)-g-poly(PEG-A) particles was assessed in-vitro using a lipophilic
      fluorescent dye as a model hydrophobic drug. Ca. 73% and 34% of the total dye
      loaded in the particles was found to be released at pH 5.0 and 7.4 in 24 h,
      respectively. The growth of human neuroblastoma cells was not affected by the
      incubation with the core-shell particles and their cleavage by-products up to 3
      mg/ml concentration. The physicochemical and the functional features support the
      potential value of the acid-cleavable poly(BA) core-poly(PEG-A) shell particles
      as carriers for the delivery of hydrophobic drugs at acidic sites.

PMID- 16996637
TI  - Bringing 'the public' into health technology assessment and coverage policy
      decisions: from principles to practice.
AB  - Those making health care coverage decisions rely on health technology assessment
      (HTA) for crucial technical information. But coverage decision-making, and the
      HTA that informs it, are also inherently political. They involve the values and
      judgments of a range of stakeholders as well as the public. Moreover, governments
      are politically accountable for their resource allocation decisions. Canadian
      policy makers are at an early stage in the design of legitimate mechanisms for
      the public to contribute to, and to be apprised of, HTA and coverage decisions.
      As they consider the options, questions arise about whom to involve (e.g., which
      publics), how to engage them (e.g., through what public involvement or
      accountability mechanisms), and for what purpose (e.g., to inform the public of
      decisions and their rationales, or to have the public directly affect those
      decisions). Often key concepts, such as the difference between public
      accountability and public participation, are not well articulated or
      distinguished in these debates. Guidance is needed regarding both rationales and
      methods for involving the public in HTA and technology coverage decisions. We
      offer a framework that clearly distinguishes specific roles for the public, and
      relates them to several layers of policy analysis and policy making where 'the
      public' may engage in different tasks. The framework offers a menu of choices for
      policy makers contemplating changes to public involvement, as well as a model
      that can be used to characterize and analyze different approaches across
      jurisdictions.

PMID- 16996638
TI  - Clinical perspectives on pulmonary systemic and macromolecular delivery.
AB  - The large epithelial surface area, the high organ vascularization, the thin
      nature of the alveolar epithelium and the immense capacity for solute exchange
      are factors that led the lung to serve as an ideal administration route for the
      application of drugs for treatment of systemic disorders. However, the deposition
      behaviour of aerosol particles in the respiratory tract depends on a number of
      physical (e.g. properties of the particle), chemical (e.g. properties of the
      drug) and physiological (e.g. breathing pattern, pulmonary diseases) factors. If
      these are not considered, it will not be possible to deposit a reproducible and
      sufficient amount of drug in a predefined lung region by means of aerosol
      inhalation. The lack of consideration of such issues led to many problems in
      inhalation drug therapy for many years mainly because physiological background of
      aerosol inhalation was not fully understood. However, over the last 20 years,
      there has been considerable progress in aerosol research and in the understanding
      of the underlying mechanisms of particle inhalation and pulmonary particle
      deposition. As a consequence, an increasing number of studies have been performed
      for the lung administration of drugs using a variety of different inhalation
      techniques. This review describes the physical and in part some of the
      physiological requirements that need to be considered for the optimization of
      pulmonary drug delivery to target certain lung regions.

PMID- 16996639
TI  - Application of two-photon microscopy to the study of cellular pharmacology of
      central neurons.
AB  - Two-photon microscopy is an especially powerful tool for combining anatomical and
      physiological experiments in the central nervous system: the possibility of
      simultaneously studying physiological phenomena in well-defined anatomical
      compartments allows fluorescence imaging of neurons in deeper layers of the
      brain. In this review we summarize the most commonly used brain preparation
      techniques together with the methods of loading neurons with fluorescent
      indicators. We will focus primarily on issues of drug delivery specifically
      related to two-photon experiments highlighting the different ways of drug
      administration. Methods of chemical stimulation via caged neurotransmitters are
      also discussed. Finally a few specific areas of two-photon applications in drug
      research on neuronal tissue are highlighted.

PMID- 16996640
TI  - Two-photon excitation imaging of exocytosis and endocytosis and determination of
      their spatial organization.
AB  - Two-photon excitation imaging is the least invasive optical approach to study
      living tissues. We have established two-photon extracellular polar-tracer (TEP)
      imaging with which it is possible to visualize and quantify all exocytic events
      in the plane of focus within secretory tissues. This technology also enables
      estimate of the precise diameters of vesicles independently of the spatial
      resolution of the optical microscope, and determination of the fusion pore
      dynamics at nanometer resolution using TEP-imaging based quantification (TEPIQ).
      TEP imaging has been applied to representative secretory glands, e.g., exocrine
      pancreas, endocrine pancreas, adrenal medulla and a pheochromocytoma cell line
      (PC12), and has revealed unexpected diversity in the spatial organization of
      exocytosis and endocytosis crucial for the physiology and pathology of secretory
      tissues and neurons. TEP imaging and TEPIQ analysis are powerful tools for
      elucidating the molecular and cellular mechanisms of exocytosis and certain
      related diseases, such as diabetes mellitus, and the development of new
      therapeutic agents and diagnostic tools.

PMID- 16996641
TI  - Intravital fluorescence microscopy in pulmonary research.
AB  - Over the last several years, microscopy as a scientific tool has reinvented
      itself evolving from a group of principally descriptive methodologies to
      encompass a wide range of primary tools and techniques to investigate the
      molecular organization of organs, tissues and cells. Advances in microscope and
      camera design, fluorescent dye technology, the development of fluorescent
      proteins as well as the advent of inexpensive powerful computers, has led to the
      feasibility of simultaneous sub micron resolution and quantitation of multiple
      concurrent molecular markers for both protein and DNA. Confocal microscopy has
      allowed optical sectioning and reconstruction of tissues in three dimensions.
      Finally, the development of multiphoton methodologies as an extension of optical
      sectioning microscopy has further improved the potential utility of this
      technology when examining living or light scattering tissues such as the lung. In
      order to illustrate the utility of two-photon methods in pulmonary biology, we
      present the application of this approach to the study of cellular trafficking in
      situ and to the study of pulmonary vasoregulation in an ex vivo rodent model.

PMID- 16996642
TI  - The chemokine network: a target in cancer biology?
AB  - Chemokine gradients are central to the movement of cells in both homeostatic and
      pathological processes. Most cancers express a complex array of chemokines that
      influence the local microenvironment through recruitment of stromal cells and by
      stimulating angiogenesis. Recently, the discovery of chemokine receptors on tumor
      cells has led to speculation that the chemokine system may be involved in cancer
      cell growth and survival, and possibly the development of site-specific spread.
      Understanding the networks of chemokines and their receptors in cancer will
      enable manipulation of this system. Both chemokines and their receptors represent
      targets for therapeutic intervention either with antibodies or small molecule
      antagonists. However, due to the complexity of the system, and the number of
      chemokines and receptors that are also expressed by normal cells, issues remain
      concerning whether systemic or local drug delivery are preferable and whether the
      redundancy of the system will compensate if one chemokine or receptor is
      targeted. Nevertheless, efficacy has been demonstrated in a number of
      experimental models. By targeting this network, it may be possible to generate
      anti-tumor immune responses by altering the chemokine and/or leukocyte balance in
      tumors; alternatively, chemokine/chemokine receptor-expressing cancer cells could
      be directly targeted.

PMID- 16996643
TI  - Expression of Snail, Slug and Sip1 in malignant mesothelioma effusions is
      associated with matrix metalloproteinase, but not with cadherin expression.
AB  - Snail, Slug and Sip1 regulate cadherin and protease expression and mediate
      epithelial-mesenchymal transition in cancer. We analyzed the expression of
      cadherins and matrix metalloproteinases (MMP) and their transcriptional
      regulators in malignant mesothelioma (MM). One hundred and ten MM specimens (86
      solid, 24 effusions) and 10 non-malignant effusions with reactive mesothelial
      cells (RMC) were analyzed for E-cadherin, N-cadherin and P-cadherin protein
      expression using immunhistochemistry. MM effusions were further analyzed for
      expression of Snail, Slug, Sip1, E-cadherin, MMP-2, MMP-9, MT1-MMP (MMP-14) and
      the MMP inhibitor TIMP-2, and for MMP-2 and MMP-9 activity using RT-PCR, Western
      blotting, immunhistochemistry and zymography. Results were analyzed for
      relationship with specimen type (biopsy versus effusion) and anatomic site
      (pleural versus peritoneal). E-cadherin, N-cadherin and P-cadherin expression was
      found in 69/110 (63%), 87/110 (79%) and 84/110 (76%) MM cases, respectively.
      Pleural and peritoneal MM showed comparable expression, but all three cadherins
      were upregulated in effusions compared to solid tumors (p<0.001). RMC were
      uniformly negative for E-cadherin and N-cadherin, and showed P-cadherin
      expression in 7/10 specimens. Immunohistochemistry localized MMP-2, MMP-9 and
      TIMP-2 to MM cells in 11/15, 14/15 and 8/15 effusions, respectively. RT-PCR
      showed direct association between MMP-2 mRNA expression level and the levels of
      MT1-MMP (p=0.027) and TIMP-2 (p=0.011). Snail protein expression showed positive
      association with MT1-MMP (p=0.016) and TIMP-2 (p=0.02) mRNA expression, but its
      expression was unrelated to MMP-2 and MMP-9 expression or activity. Snail, Slug
      and Sip1 levels did not show inverse association with E-cadherin levels. Our data
      show that E-cadherin and N-cadherin are selectively expressed in malignant
      mesothelial cells, and that P-cadherin and N-cadherin are expressed with similar
      frequency in MM. In agreement with our earlier data for ovarian carcinoma,
      cadherin expression is upregulated in effusions compared to solid lesions. The
      increased E-cadherin expression in effusions may be related to lack of negative
      regulation at the epigenetic level. The relationship between Snail and MMP in MM
      is uncertain at present.

PMID- 16996645
TI  - Using hierarchical levels for urban ecology.

PMID- 16996646
TI  - Can we improve doctors' hand hygiene on ward rounds?

PMID- 16996647
TI  - Increased expression of mu opioid receptors in animals susceptible to diet
      induced obesity.
AB  - Stimulation of mu opioid receptors preferentially increases the intake of a high
      fat diet. In this paper we investigated whether there was a difference in the
      expression of mu opioid receptors between animals susceptible (Osborne-Mendel) or
      resistant (S5B/Pl) to obesity induced by eating a high fat diet.
      Immunohistochemical studies demonstrated that Osborne-Mendel rats eating a chow
      diet had an increased number of mu opioid receptors in the arcuate nucleus when
      compared to S5B/Pl rats. These immunohistochemical findings were supported by
      Real Time-PCR which demonstrated that the mRNA level of mu opioid receptors was
      also increased in the hypothalamus of Osborne-Mendel rats compared to S5B/Pl
      rats. Low doses of the mu opioid receptor agonist DAMGO [d-Ala(2)-N-Me-Phe(4)
      Glycol(5)]-enkephalin administered to Osborne-Mendel rats caused a significant
      increase in the preference for a diet high in fat. The same doses of DAMGO
      switched the diet preference of S5B/Pl rats to high fat but did not significantly
      increase food intake. The combination of these findings suggests that the
      increased levels of hypothalamic mu opioid receptors in Osborne-Mendel rats may
      contribute to their preference for a diet high in fat and increase their
      susceptibility to becoming obese.

PMID- 16996648
TI  - Biophysical delivery of peptides: applicability for cancer therapy.
AB  - There is a current trend towards evaluation of molecular agents for treatment of
      a variety of ailments, including cancer. One class of such biomolecules is
      proteins, and their shortened versions, peptides. Use of peptidic entities has
      been hindered by poor bioavailability in vivo and the high cost involved in mass
      producing these macromolecular drugs. The need for localized delivery is being
      met with the development of various biophysical means, which include devices and
      aids, mainly transdermal and invasive implants. In addition, various cell-based
      delivery modalities, which include the use of spore-forming bacteria and stem
      cells, are being explored. This review discusses these methods in turn, and
      examines ways by which these can be enhanced for peptide delivery to tumors.

PMID- 16996649
TI  - A metabolic link between S-adenosylhomocysteine and polyunsaturated fatty acid
      metabolism in Alzheimer's disease.
AB  - There is evidence that vascular risk factors contribute to the pathology of
      Alzheimer's disease. Increased concentrations of circulating homocysteine are
      associated with vascular risk factors and Alzheimer's disease but the mechanisms
      involved are unclear. Homocysteine inhibits the hydrolysis of S
      adenosylhomocysteine (SAH) which is a product inhibitor of S-adenosylmethionine
      (SAM) dependent methyltransferase reactions. It has been shown previously that
      SAH inhibits phosphatidylethanolamine N-methyltransferase (PEMT) in the liver.
      The activity of PEMT in the liver plays an important role in the methylation of
      phosphatidylethanolamine (PE) to phosphatidylcholine (PC) and the delivery of
      essential polyunsaturated fatty acids (PUFAs) to peripheral tissues. In the
      present study, the plasma concentrations of SAH, SAM and homocysteine and the
      erythrocyte composition of phosphatidylcholine (PC), phosphatidylethanolamine
      (PE) and their respective polyunsaturated fatty acid concentrations were
      determined in 26 patients with Alzheimer's disease and compared to those in 29
      healthy control subjects. There was a significant increase in the plasma
      concentrations of SAH (p<0.001) and homocysteine (p<0.001) and a significant
      increase in the plasma concentrations of SAM (p<0.001) in the Alzheimer's
      patients. A significant positive correlation was found between the plasma
      concentrations of SAH and homocysteine (r=0.738, p<0.001). There was a negative
      correlation between the plasma concentrations of homocysteine and the ratio of
      SAM/SAH (r=-0.637, p<0.01). There was a significant decrease in the erythrocyte
      content of PC (p<0.001) and an increase in the erythrocyte content of PE
      (p<0.001) in the Alzheimer's patients. Plasma SAH concentrations were negatively
      related to erythrocyte PC concentrations (r=-0.286, p<0.01) and positively
      related to erythrocyte PE concentrations (r=0.429, p<0.001). The erythrocyte PC
      from Alzheimer's patients had a significant depletion of docosahexaenoic acid
      (DHA) (p<0.001) while there was no significant difference in the DHA content of
      erythrocyte PE. There was a significant negative correlation between plasma SAH
      and the DHA composition of erythrocyte PC (r=-0.271, p<0.001). This data may
      reflect the inhibition of hepatic PEMT activity by SAH in Alzheimer's disease.
      The decreased mobilization of DHA from the liver into plasma and peripheral
      tissues may increases the risk of atherosclerosis and stroke leading to chronic
      cerebral hypoperfusion. The evidence suggests that a metabolic link between the
      increased production of SAH and phospholipid metabolism may contribute to
      cerebrovascular and neurodegenerative changes in Alzheimer's disease.

PMID- 16996650
TI  - Effect of aging on cerebral A1 adenosine receptors: A [18F]CPFPX PET study in
      humans.
AB  - Cerebral A(1) adenosine receptors (A(1)AR) fulfill important neuromodulatory and
      homeostatic functions. The present study examines possible age-related A(1)AR
      changes in living humans by positron emission tomography (PET) and the A(1)AR
      ligand [(18)F]CPFPX. Thirty-six healthy volunteers aged 22-74 years were
      included. The apparent binding potential (BP'2) of [(18)F]CPFPX in various
      cerebral regions was calculated non-invasively using the cerebellum as reference
      region. In addition, the total distribution volume (DV't) was assessed in 10
      subjects undergoing arterial blood sampling. There was no significant association
      between regional DV't and age, gender, caffeine consumption or sleep duration.
      BP'2 showed a significant age-dependent decrease in all regions except cingulate
      gyrus (p=0.062). The BP'2 decline ranged from -17% (striatum) to -34%
      (postcentral gyrus), the average cortical decline being -23%. There was no
      significant effect of gender, caffeine consumption and sleep duration on BP'2. In
      line with in vitro animal studies, the present in vivo PET study detected an age
      dependent A(1)AR loss in humans that may be of pathophysiological importance in
      various neurological diseases associated with aging. Because of the discrepant
      results of the invasive (DV't) and the non-invasive (BP'2) analyses the present
      study needs further validation.

PMID- 16996651
TI  - Synthesis and biological activity of 8-azapurine and pyrazolo[4,3-d]pyrimidine
      analogues of myoseverin.
AB  - The trisubstituted purine myoseverin has been recently identified as a novel
      inhibitor of microtubule assembly. To analyze the effects of modifying its
      heterocyclic skeleton, we prepared 8-azapurine and pyrazolo[4,3-d]pyrimidine
      analogues of myoseverin and compared their biological activities. Rearrangement
      of nitrogen atoms in the heterocycle changes the affinity of the compounds to
      purified tubulin, as demonstrated by the results of polymerization assays, and
      affects the proliferation of cancer cell lines. Surprisingly, compound E2GG, a
      pyrazolo[4,3-d]pyrimidine analogue of myoseverin, displayed inhibitory activity
      towards both tubulin polymerization and the activity of cyclin-dependent kinases
      1, 2 and 7. Such a dual specificity-inhibitor offers a starting point for
      developing a novel class of antiproliferative agents.

PMID- 16996652
TI  - Air to fat and blood to fat distribution of volatile organic compounds and drugs:
      linear free energy analyses.
AB  - Partition coefficients, K(fat), from air to human fat and to rat fat have been
      collected for 129 volatile organic compounds, VOCs. A linear free energy
      relationship, LFER, correlates the 129 values of log K(fat) with R(2)=0.958 and a
      standard deviation, S.D., of 0.194 log units. Use of training and test sets gives
      a predictive assessment of around 0.20 log units. Combination of log K(fat) with
      our previously listed values of log K(blood) enables blood/plasma to fat
      partition coefficients, as log P(fat), to be obtained for 126 VOCs. These values
      can be correlated with R(2)=0.847, S.D.=0.304 log units; the latter is also our
      assessment of the predictive capability of the LFER. Values of log P(fat) have
      been collected for 46 drugs, and can be fitted to an LFER with R(2)=0.811 and
      S.D.=0.355 log units. Unlike partition into brain or muscle, the data for VOCs
      and drugs cannot be combined. There are marked discrepancies for PCBs for which
      partition from blood/plasma into fat is very much less than that calculated from
      the data on VOCs or from the data on drugs.

PMID- 16996653
TI  - QSAR analysis of tyrosine kinase inhibitor using modified ant colony optimization
      and multiple linear regression.
AB  - Quantitative structure-activity relationship (QSAR) models of inhibiting action
      of some analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline on epidermal
      growth factor receptor tyrosine kinase were constructed using modified ant colony
      optimization (ACO) method. As a comparison to this method, the evolutionary
      algorithm (EA) was also tested. It has been demonstrated that the modified ACO is
      a useful tool for variable selection comparable to EA. In the selected
      descriptors, electronic descriptor sigma(Y)(-) is the most important descriptor
      in predicting EGFR inhibitory activity. Electron-donating groups such as Y
      substituents enhance the activity as evident by negative sigma(Y)(-). In
      addition, for quinazoline substituents, nitro group has a large deactivating
      effect.

PMID- 16996654
TI  - Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H
      benzimidazol-2-ylthioacetylpiperazine derivatives.
AB  - Piperazine derivatives of 5(6)-substituted-(1H-benzimidazol-2-ylthio)acetic acids
      were synthesized by using two methods and studied for antihelminthic activity.
      The antiparasitic screening showed that compounds 18-24 exhibited higher activity
      against Trichinella spiralis in vitro in comparison to methyl 5-(propylthio)-1H
      benzimidazol-2-yl-carbamate (albendazole). Most active were compounds 2-({2-[4-(4
      chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21 and 2-{[2-oxo-2
      (4-benzhydrylpiperazin-1-yl)ethyl]thio}-5(6)-methyl-1(H)-benzimidazole 19 as well
      as 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)
      benzimidazole 23 with efficacy of 96.0%, 98.4% and 100%, respectively. The tested
      derivatives 15-19 and 20-23 were less active against Syphacia obvelata in vivo
      than albendazole and exhibited the same efficacy as piperazine, but in twice
      lower concentration.Compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2
      oxoethyl}thio)-1H-benzimidazole 21, 1,4-bis[(5(6)-methyl-1(H)-benzimidazol-2
      ylthio)acetyl]piperazine 17 and 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2
      oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 had higher efficacies of 73%,
      76%, and 77%, respectively.

PMID- 16996655
TI  - Novel derivatives of methyl and ethyl 2-(4-oxo-8-aryl-2H-3,4,6,7
      tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl)acetates from biologically active 1
      aryl-2-hydrazinoimidazolines: synthesis, crystal structure and antiproliferative
      activity.
AB  - The 1-aryl-2-hydrazinoimidazolines (2a-h) were directly obtained from appropriate
      1-aryl-2-methylthioimidazolines (1a-h) by condensation reaction with hydrazine
      hydrate. Antimicrobial activities of two 1-aryl-2-hydrazinoimidazolines (2b and
      2e) are presented. Their chemical structures were confirmed by IR, (1)H NMR, EI
      MS and elemental analysis. The susceptibility of Gram-positive and Gram-negative
      bacterial strains, mould and yeast-like fungi strains to synthesized compounds
      and the MIC values against two reference strains of bacteria were determined. The
      strongest antibacterial activity for compound 2b in relation to reference Gram
      negative Escherichia coli ATCC 25922 bacterial strain with minimal inhibitory
      concentration (MIC) value of 3.91micro g mL(-1) was found. Compound 2b showed
      superior activity (MIC) to ampicillin and comparable to chloramphenicol. A novel
      compound 2e was found to be effective against E. coli ATCC 25922 and
      Staphylococcus aureus ATCC 25923 at concentrations of 7.81micro g mL(-1) and
      15.62micro g mL(-1), respectively. Compound 2e revealed antibacterial activity
      against E. coli ATCC 25922, superior to ampicillin and inferior to
      chloramphenicol. Against S. aureus ATCC 25923 strain tested, compound 2e
      demonstrated MIC value inferior to ampicillin and chloramphenicol. Moreover, the
      synthesis, crystal structure and antiproliferative activity of novel derivatives
      of methyl and ethyl 2-(4-oxo-8-aryl-2H-3,4,6,7-tetrahydroimidazo[2,1
      c][1,2,4]triazin-3-yl)acetates (3a-f and 3g-j) are presented. These compounds
      were obtained from 1-aryl-2-hydrazinoimidazolines (2a-f) by the addition and
      cyclization reactions with fumaric acid esters. Molecular structures of these
      compounds were confirmed by elemental analysis, IR, (1)H NMR, (13)C NMR, EI-MS
      and by X-ray crystallography (for 3g). The tested imidazotriazines 3e, 3i and 3j
      exhibited anticancer activities towards the following cancer cells: LS180 (ECACC
      87021202, human Caucasian colon adenocarcinoma cells), SiHa (ECACC 85060701,
      uterus cancer cells), and T47D (ECACC 85102201, human breast carcinoma cells).
      Compounds 3i and 3j having comparable GI values (above 50%) towards uterus cancer
      cell line (SiHa) at both examined concentrations (10micro g mL(-1) and 50micro g
      mL(-1)) were found to be the most effective against this cancer cell line; their
      GI factors were 53%, 51% and 62%, 55%, respectively, in both examined
      concentrations (10micro g mL(-1) and 50micro g mL(-1)). Furthermore, the
      distinctly marked lower cytotoxicity of tested imidazotriazines 3i and 3j against
      normal cell lines (HSF, human skin fibroblast cells and Vero African Green Monkey
      Kidney cells, GMK clone) and almost 2-times higher against the majority of cancer
      cell lines was confirmed.

PMID- 16996656
TI  - Synthesis, antimicrobial activity and QSARs of new benzoxazine-3-ones.
AB  - New ethyl 3,4-dihydro-3-oxo-4,6,7-trisubstituted-2H-1,4-benzoxazine-2-acetate
      derivatives were synthesized and their structures were elucidated by IR, (1)H NMR
      and mass spectral data. Antimicrobial activity of the compounds was investigated
      by using the method of twofold serial dilution technique against different Gram
      positive, Gram-negative bacteria and some Candida species in comparison to
      standard drugs. Microbiological results indicated that the synthesized compounds
      possessed a broad spectrum of activity having MIC values of 6.25-100 micro g/ml
      against the tested microorganisms. The QSAR analysis of a set of these compounds
      tested for growth inhibitory activity against Candida krusei was performed by
      using the computer-assisted multiple regression procedure. The activity
      contributions for substituent effects of these compounds were determined from the
      correlation equation for predictions of the lead optimization.

PMID- 16996657
TI  - Design, synthesis and cytotoxic properties of novel 1-[4-(2
      alkylaminoethoxy)phenylcarbonyl]-3,5-bis(arylidene)-4-piperidones and related
      compounds.
AB  - The 3,5-bis(arylidene)-4-piperidones 1 contain the 1,5-diaryl-3-oxo-1,4
      pentadienyl pharmacophore which is considered to interact at a complementary
      binding site in susceptible neoplasms. The hypothesis was formulated that the
      presence of an acyl group attached to the piperidyl nitrogen atom in series 1 may
      interact with an additional binding site thereby enhancing cytotoxic potencies.
      This concept led to the synthesis of various N-acyl-3,5-bis(arylidene)-4
      piperidones 3-7 many of which displayed significant cytotoxicity towards a
      variety of cancer cell lines. A comparison of the potencies between the compounds
      in series 1 and the related nonquaternary analogues 3-6 revealed that in
      approximately half of the comparisons made, the N-acyl analogues had increased
      potencies.

PMID- 16996658
TI  - Cyclic and branched acyl chain galactoglycerolipids and their effect on anti
      tumor-promoting activity.
AB  - Fifteen new galactoglycerolipid analogues, in which one or two branched,
      alicyclic or aromatic acyl chains are linked to 2-O-beta-D-galactosylglycerol (6'
      position or 1,6' positions), were prepared and tested for their anti-tumor
      promoting activity using a short-term in vitro assay for Epstein-Barr virus early
      antigen (EBV-EA) activation. All compounds were active in inhibiting the EBV
      activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate
      (TPA), the branched compounds resulting in the most active glycoglycerolipid
      analogues of the series. The branched 2-O-[6-O-(3-methylbutanoyl)-beta-D
      galactopyranosyl]-sn-glycerol (1a) and the structurally related alicyclic 2-O-[6
      O-(2-cyclohexylethanoyl)-beta-D-galactopyranosyl]-sn-glycerol (1d), when tested
      in an in vivo two-stage carcinogenesis test, exhibited inhibitory effects on
      mouse skin tumor promotion.

PMID- 16996659
TI  - Is serum albumin a good marker for malnutrition in the physically impaired
      elderly?
AB  - BACKGROUND AND AIMS: Although serum albumin is well known as a marker of
      nutritional status, it has remained unclear whether impaired physical function
      affects serum albumin concentrations in older people. We examined whether
      hypoalbuminemia can be used as a marker of malnutrition in elderly subjects with
      various levels of physical impairment. METHODS: A total of 262 elderly subjects
      without acute illness were enrolled from various geriatric settings. For the
      nutritional assessment, serum albumin, total cholesterol, anthropometric
      measurements, and subjective global assessment (SGA) were determined. Physical
      function was evaluated by rating score of activity of daily living (ADL).
      RESULTS: As a whole, participants' serum albumin levels correlated with various
      nutritional parameters including anthropometric measurements and levels of serum
      total cholesterol as well as the SGA evaluation. However, after adjusting for age
      and gender, serum albumin levels in participants with a low ADL function did not
      correlate with nutritional parameters. Approximately 80% participants with low
      ADL function who were evaluated as being well nourished according to SGA
      evaluation had serum albumin levels lower than 35 g/l. CONCLUSIONS: The utility
      of serum albumin and the traditional cutoff (35 g/l) in older people with low ADL
      function is questionable even among those without inflammation.

PMID- 16996660
TI  - Effect of an enteral diet supplemented with a specific blend of amino acid on
      plasma and muscle protein synthesis in ICU patients.
AB  - BACKGROUND & AIM: Polytrauma patients are characterized by a negative nitrogen
      balance and muscle wasting. Standard nutrition is relatively inefficient to
      improve muscle protein turnover. The aim of this study was to investigate the
      effect of enteral nutrition (EN) supplemented with specific amino acids on
      protein metabolism in polytrauma patients. METHODS: In a double blind study, 12
      polytrauma patients were randomized to receive EN supplemented with either a
      mixture of cysteine, threonine, serine and aspartate (AA patients) or alanine at
      isonitrogenous levels (Ala patients). An intravenous infusion of l-[1-(13)C]
      leucine was performed in the fed state between day 9 and 12 post-injury (Df) in
      patients and in a group of healthy volunteers (n=8) (EN+Ala) to measure whole
      body leucine kinetics, plasma and muscle protein synthesis rates. Nitrogen
      balance, 3-methyl histidine excretion were measured from day 3 to Df. RESULTS:
      The contribution of total plasma proteins to whole body protein synthesis was
      greatly increased, from 11% in healthy volunteers to about 25% in polytrauma
      patients. AA supplementation had no effect on nitrogen balance, leucine kinetics
      or plasma protein synthesis in patients. In contrast, the urinary excretion of 3
      methyl histidine tended to decrease along the study in the AA supplemented group
      compared to an increase in the Ala group. Muscle protein synthesis tended to be
      higher in the AA group than in the Ala group (46%, P=0.065). CONCLUSION: During
      injury, an increased supply of cysteine, threonine, serine and aspartate could be
      able to better cover the specific amino requirements, thus resulting in improved
      muscle protein synthesis without impairment of acute phase protein synthesis.

PMID- 16996661
TI  - Preparation and immunogenic properties of a recombinant West Nile subunit
      vaccine.
AB  - While several West Nile vaccines are being developed, none are yet available for
      humans. In this study aimed at developing a vaccine for humans, West Nile virus
      (WNV) envelope protein (E) and non-structural protein 1 (NS1) were produced in
      the Drosophila S2 cell expression system. The C-terminal 20% of the E protein,
      which contains the membrane anchor portion, was deleted, thus allowing for
      efficient secretion of the truncated protein (80E) into the cell culture medium.
      The proteins were purified by immunoaffinity chromatography (IAC) using
      monoclonal antibodies that were flavivirus envelope protein group specific (for
      the 80E) or flavivirus NS1 group specific (for NS1). The purified proteins were
      produced in high yield and used in conjunction with adjuvant formulations to
      vaccinate mice. The mice were tested for both humoral and cellular immune
      responses by a plaque reduction neutralization test and ELISA, and by lymphocyte
      proliferation and cytokine production assays, respectively. The results revealed
      that the 80E and the NS1 proteins induced both high-titered ELISA and
      neutralizing antibodies in mice. Splenocytes from immunized mice, cultured in
      vitro with the vaccine antigens as stimulants, showed excellent proliferation and
      production of cytokines (IFN-gamma, IL-4, IL-5, and IL-10). The level of antigen
      stimulated lymphocyte proliferation and cytokine production was comparable to the
      level obtained from mitogen (phytohemagglutinin or pokeweed) stimulation,
      indicating a robust cellular response as well. These findings are encouraging and
      warrant further in vivo studies to determine the protective efficacy of the WNV
      vaccine candidate.

PMID- 16996662
TI  - Injectable polymer microspheres enhance immunogenicity of a contraceptive peptide
      vaccine.
AB  - Advanced contraceptive peptide vaccines suffer from the unavailability of
      adjuvants capable of enhancing the antibody response with acceptable safety. We
      sought to overcome this limitation by employing two novel poly(lactic-co-glycolic
      acid) (PLGA) microsphere formulations to deliver a synthetic human chorionic
      gonadotropin (hCG) peptide antigen co-synthesized with a T-cell epitope from
      tetanus toxoid (TT), C-TT2-CTP35: surface-conjugated immunogen to induce
      phagocytosis; and encapsulated peptide to provide a depot effect, with MgCO(3) co
      encapsulated in the polymer to neutralize acidity from the biodegrading PLGA
      polyester. A single immunization of encapsulated peptide in rabbits elicited a
      stronger antibody response with equivalent duration relative to a positive
      control--three injections of the peptide administered in a squalene-based water
      in-oil emulsion. Surface-conjugated peptide was less effective but enhanced
      antibody levels at 1/5 the dose, relative to soluble antigen. Most remarkable and
      unexpected was the finding that co-encapsulation of base was essential to attain
      the powerful adjuvant effect of the PLGA-MgCO(3) system, as the MgCO(3)-free
      microspheres were completely ineffective. A promising contraceptive hCG peptide
      vaccine with acceptable side effects (i.e., local tissue reactions) was achieved
      by minimizing PLGA and MgCO(3) doses, without significantly affecting antibody
      response.

PMID- 16996663
TI  - Development of an OspC-based tetravalent, recombinant, chimeric vaccinogen that
      elicits bactericidal antibody against diverse Lyme disease spirochete strains.
AB  - Lyme disease is the most common arthropod-borne disease in North America and
      Europe. At present, there is no commercially available vaccine for use in humans.
      Outer surface protein C (OspC) has antigenic and expression characteristics that
      make it an attractive vaccine candidate; however, sequence heterogeneity has
      impeded its use as a vaccinogen. Sequence analyses have identified 21 well
      defined OspC phyletic groups or "types" (designated A-U). In this report we have
      mapped the linear epitopes presented by OspC types B, K, and D during human and
      murine infection and exploited these epitopes (along with the previously
      identified type A OspC linear epitopes) in the development of a recombinant,
      tetravalent, chimeric vaccinogen. The construct was found to be highly
      immunogenic in mice and the induced antibodies surface labeled in vitro
      cultivated spirochetes. Importantly, vaccination induced complement-dependent
      bactericidal antibodies against strains expressing each of the OspC types that
      were incorporated into the construct. These results suggest that an effective and
      broadly protective polyvalent OspC-based Lyme disease vaccine can be produced as
      a recombinant, chimeric protein.

PMID- 16996664
TI  - Influenza vaccination in healthy children.

PMID- 16996665
TI  - The effects of work experience, lift frequency and exposure duration on low back
      muscle oxygenation.
AB  - BACKGROUND: Previous studies have shown changes in low back muscle oxygenation
      after static muscle contractions or short-term dynamic lifting exertions. The aim
      of this study was to document the changes in low back muscle oxygenation during
      prolonged lifting activity over an entire workday as of function of work
      experience and lift frequency. METHODS: Four novice and six experienced subjects
      participated in a lifting study in which they lifted load with a given weight at
      one of five different frequencies (2, 4, 8, 10, 12 lifts/min) for an 8-h period.
      Oxygen saturation of the left and right erector spinae was measured continuously
      and non-invasively using near-infrared spectroscopy during each lifting session.
      FINDINGS: Exposure duration had a statistically significant effect on muscle
      oxygenation level (P<0.0001). Oxygen saturation in the erector spinae increased
      during the 8-h lifting period. As lift frequency increased, back muscle
      oxygenation in experienced subjects also increased. In general, the increase in
      muscle oxygenation for experienced subjects was less than that for novice
      subjects. INTERPRETATION: This study suggested that the requirement of oxygen for
      the low back muscle in a typical industrial lifting job increased over time and
      experienced workers responded differently from the novice subjects. These
      findings may provide more insight into the physiological changes of the working
      muscle and the potential risks of developing muscle injury.

PMID- 16996666
TI  - Biomechanical comparison of double-loaded suture anchors using arthroscopic Mason
      Allen stitches versus traditional transosseous suture technique and modified
      Mason-Allen stitches for rotator cuff repair.
AB  - BACKGROUND: In recent studies objective evaluations have demonstrated that
      arthroscopic rotator cuff repairs can have higher failure rates than open
      repairs. Thus, there is a need for a stronger tissue-holding stitch for
      arthroscopical repair. The purpose of this study was to compare the biomechanical
      properties of traditional open transosseous suture technique and modified Mason
      Allen stitches versus double-loaded suture anchors and arthroscopic Mason-Allen
      stitches in rotator cuff repair. METHODS: In 20 sheep shoulders the infraspinatus
      tendons were dissected from their insertion and were randomized to 2 repair
      groups: (1) repair with transosseous suture and modified Mason-Allen stitches,
      (2) repair with double loaded bioabsorbable suture anchors and arthroscopic Mason
      Allen stitches: Both groups were coupled with braided, nonabsorbable polyester
      (Ethibond) suture sized USP No. 2. All repairs were cyclically loaded from 10 to
      180N with the use of a materials testing machine. The number of cycles to gap
      formation of 5 and 10mm at the repair site and the mode of failure were recorded.
      RESULTS: The number of cycles to 5-mm gap was mean 634 (SD 106) for group 1 and
      mean 750 (SD 107) for group 2 (P<0.026). The corresponding values to 10-mm gap
      were mean 1573 (SD 161) for group 1, and mean 1789 (SD 183 cycles) for group 2
      (P<0.012). In group 2 the mode of failure occurred by tissue pull-out, whereas in
      group 1 the failure occurred by a mixture of suture breakage and pull-out.
      CONCLUSIONS: This time-zero study demonstrates that the combination of
      bioabsorbable suture anchors and arthroscopic Mason-Allen stitches provides
      strength superior to that of the modified Mason-Allen transosseous suture
      technique under isometric cyclic loading conditions. However, additional
      evaluation is needed to examine the effects on the sustained strength of the
      repair throughout the healing process.

PMID- 16996667
TI  - Sulfur (S)-induced enhancement of iron plaque formation in the rhizosphere
      reduces arsenic accumulation in rice (Oryza sativa L.) seedlings.
AB  - The effects of two sulfur (S) sources (SO(4)(2-), S(0)), and three rates of S
      application (0, 30, 120 mgS/kg) on the formation of iron plaque in the
      rhizosphere, and on the root surface of rice, and As (arsenic) uptake into rice
      (Oryza sativa L.) were studied in a combined soil-sand culture experiment.
      Significant differences in As uptake into rice between +S and -S treatments were
      observed in relation to S sources, and rates of S application. Concentrations of
      As in rice shoots decreased with increasing rates of S application. The mechanism
      could be ascribed to sulfur, induced the formation of iron plaque, since
      concentrations of Fe in iron plaque on quartz sands in the rhizosphere, and on
      the root surface of rice increased with increasing rates of S application. The
      results suggest that sulfur fertilization may be important for the development
      approaches to reducing As accumulation in rice.

PMID- 16996668
TI  - Neighborhood microclimates and vulnerability to heat stress.
AB  - Human exposure to excessively warm weather, especially in cities, is an
      increasingly important public health problem. This study examined heat-related
      health inequalities within one city in order to understand the relationships
      between the microclimates of urban neighborhoods, population characteristics,
      thermal environments that regulate microclimates, and the resources people
      possess to cope with climatic conditions. A simulation model was used to estimate
      an outdoor human thermal comfort index (HTCI) as a function of local climate
      variables collected in 8 diverse city neighborhoods during the summer of 2003 in
      Phoenix, USA. HTCI is an indicator of heat stress, a condition that can cause
      illness and death. There were statistically significant differences in
      temperatures and HTCI between the neighborhoods during the entire summer, which
      increased during a heat wave period. Lower socioeconomic and ethnic minority
      groups were more likely to live in warmer neighborhoods with greater exposure to
      heat stress. High settlement density, sparse vegetation, and having no open space
      in the neighborhood were significantly correlated with higher temperatures and
      HTCI. People in warmer neighborhoods were more vulnerable to heat exposure
      because they had fewer social and material resources to cope with extreme heat.
      Urban heat island reduction policies should specifically target vulnerable
      residential areas and take into account equitable distribution and preservation
      of environmental resources.

PMID- 16996669
TI  - The cognitive structuring of patient delay in breast cancer.
AB  - The reasons women give for delaying diagnosis of breast cancer symptoms are
      numerous and striking. Yet none prove reliable as indicators of those who will
      delay, and most women overcome all barriers to seek immediate diagnosis. This
      study looks more deeply into the reasoning of symptomatic women sustaining
      confidence in a decision to delay diagnosis of self-discovered breast symptoms.
      Using argument and heuristic analysis, we examined the structure and soundness of
      the reasoning in interviews with 28 women from the San Francisco Bay area
      monitoring breast symptoms. Fifteen women were sustaining decisions to delay
      seeking diagnosis. Their arguments' structure and soundness, and their dependence
      on heuristic strategies, were compared with those of women who did not delay.
      Prompt diagnosis-seekers used vivid stories of other women with breast cancer to
      explain their diagnosis seeking, and the others used similar stories to justify
      on-going decisions to delay. Diagnosis-seekers offered more arguments for doing
      so than for delay. Delayers offered fewer arguments for seeking diagnosis and
      many more for delay. Delayers abandoned sound and usually compelling arguments to
      seek diagnosis, relying instead on false information, poorly reasoned arguments,
      and self-created dominance structures around decisions to delay. Decisions to
      delay were resilient, yet required maintenance to sustain. Intervention studies
      aimed at decreasing patient delay should address the thinking process by
      questioning reliance on mistaken claims of control over possibly advancing
      cancer, satisficing (corner-cutting to arrive at a minimally adequate solution to
      achieve a goal) when scheduling diagnostic visits, simulating a benign diagnosis
      rather than the prevention of late-staged cancer, prioritizing fear control over
      protection of life. Interventions might also include challenging mistaken
      analogies and the too facile abandonment of sound arguments for seeking prompt
      diagnosis.

PMID- 16996670
TI  - Racial disparities in low birthweight and the contribution of residential
      segregation: a multilevel analysis.
AB  - This study investigates the geography of racial disparities in low birthweight in
      New York City by focusing on racial residential segregation and its effect on the
      risk of low birthweight among African-American infants and mothers. This cross
      sectional multilevel analysis uses birth records at the individual level
      (n=96,882) and racial isolation indices at the census tract or neighborhood level
      (n=2095) to measure their independent and cross-level effects on low birthweight.
      This study found that residential segregation and neighborhood poverty operate at
      different scales to increase the risk of low birthweight. At the neighborhood
      scale residential segregation is positively and significantly associated with low
      birthweight, after controlling for individual-level risk factors and neighborhood
      poverty. Residential segregation explains neighborhood variation in low
      birthweight means and race effects across census tracts, which cannot be
      accounted for by neighborhood poverty alone. At the individual scale-increasing
      levels of residential segregation does not significantly reduce or exacerbate
      individual-level risk factors for low birthweight; whereas increasing levels of
      neighborhood poverty significantly eliminates the race effect and reduces the
      protective effect of being foreign-born on low birthweight, after controlling for
      other individual-level risk factors and residential segregation. These findings
      are contradictory to previous health research that shows protective mechanisms
      associated with ethnic density in local areas. It is likely that structural
      factors underlying residential segregation, i.e., racial isolation, impose
      additional stressors on African-American women that may offset or disguise
      positive attributes associated with ethnic density. However, as poverty is
      concentrated within these neighborhoods, differences between races in low
      birthweight cease to exist. This study demonstrates that residential segregation
      and neighborhood poverty are important determinants of racial disparity in low
      birthweight in New York City.

PMID- 16996671
TI  - Transient hypolocomotion in rats repeatedly exposed to phencyclidine: an
      appraisal of motor function and motivation.
AB  - Spontaneous locomotion in rats is reduced about 20 h following phencyclidine
      (PCP) exposure. Our primary purpose was to test if locomotor irregularities would
      outlast drug withdrawal and be modulated by a periodic auditory stimulation
      during or after repeated injections. To circumscribe plausible interpretations,
      motor coordination and motivation were assessed as well. 10 mg/kg of PCP
      decreased spontaneous locomotion during the injection period whether or not a
      sound was presented. Those effects did not persist after a 7-day washout. Motor
      coordination and motivation to perform a variety of goal-driven conducts in the
      presence or absence of reinforcement were all unaffected by PCP treatment. The
      generalized hypolocomotor effects induced by PCP likely resulted from an
      inability to self-generate behaviors. These deficiencies were apparent in
      contexts where response production was not clearly specified nor supported,
      regardless of reward contingency.

PMID- 16996672
TI  - Cholinergic modulation of periaqueductal grey neurons: does it contribute to
      epileptogenesis after organophosphorus nerve agent intoxication?
AB  - Previous work has shown that a single focal microinjection of the unselective
      cholinergic agonist, carbachol, into the periaqueductal grey (PAG) of the
      midbrain is sufficient to induce forebrain seizures in rats. In order to
      determine the cholinergic mechanisms underlying epileptogenesis at the cellular
      and network level of the PAG, we performed whole-cell recordings from rat PAG
      neurons in vitro and examined how the activation of muscarinic and nicotinic
      receptors modulates cellular excitability and synaptic responses. Stimulation of
      muscarinic receptors produced either a pirenzepine-sensitive depolarization (40%
      of PAG neurons), or a gallamine-sensitive hyperpolarization (20%), suggesting the
      involvement of M1 and M2 receptors, respectively. In the remaining neurons (40%),
      no change was observed. Voltage-clamp recordings showed that muscarinic
      depolarization resulted from the inhibition of a resting K(+) current, in part
      accompanied by simultaneous activation of a presumed non-selective cation
      current. Muscarinic hyperpolarization was caused by the activation of a G protein
      coupled, inwardly rectifying K(+) current. Stimulation of muscarinic receptors
      enhanced the frequency of spontaneous inhibitory postsynaptic currents (IPSCs),
      but strongly suppressed evoked IPSCs. In addition, nicotine almost doubled the
      frequency of miniature IPSCs. Based on our findings and the network properties of
      the PAG, we advance a scenario in which excessive stimulation of cholinergic
      receptors would substantially contribute to generalized seizures after
      organophosphorus nerve agent poisoning.

PMID- 16996673
TI  - Curcumin down regulates smokeless tobacco-induced NF-kappaB activation and COX-2
      expression in human oral premalignant and cancer cells.
AB  - Smokeless tobacco (ST) consumption is a major cause of oral cancer in South East
      Asia including India. Recently, we showed that exposure to smokeless tobacco
      extract (STE) (khaini) results in increased expression and activation of nuclear
      factor-kappaB (NF-kappaB) and its downstream target cyclooxygenase-2 (COX-2) in
      human oral cell systems in vitro. The present study was designed to test the
      hypothesis that curcumin may inhibit the activation of NF-kappaB in ST exposed
      oral premalignant and cancer cells. Exposure of oral premalignant and cancer
      cells to curcumin resulted in significant decrease in cell viability and induced
      apoptosis. STE-induced nuclear translocation and DNA-binding activity of NF
      kappaB were inhibited in curcumin pretreated oral premalignant and cancer cells
      in vitro. Curcumin treatment led to decreased expression of NF-kappaB and COX-2.
      The tobacco specific nitrosamine, 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone
      (NNK), is one of the carcinogenic components of STE (khaini). We demonstrate that
      curcumin pretreatment abrogated NNK-induced activation of NF-kappaB and COX-2
      expression, suggesting that NNK is one of the factors in STE (khaini) modulated
      by curcumin. In conclusion, our findings demonstrate for the first time that
      curcumin downregulates STE (khaini) or NNK-induced NF-kappaB and COX-2 in oral
      premalignant and cancer cells in vitro.

PMID- 16996674
TI  - An in vitro quantitative antibacterial analysis of amalgam and composite resins.
AB  - OBJECTIVES: Antibacterial properties of restorative dental materials such as
      amalgam and composite resins may improve the restorative treatment outcome. This
      study evaluates the antibacterial properties of three composite resins: Z250,
      Tetric Ceram, P60 and a dental amalgam in vitro. METHODS: Streptococcus mutans
      and Actinomyces viscosus served as test microorganisms. Three quantitative
      microtiter spectrophotometric assays were used to evaluate the effect of the
      restorative materials on: (i) early-stage biofilm using a direct contact test
      (DCT); (ii) planktonic bacterial growth; (iii) bacterial growth in the materials'
      elute. For comparison purposes, agar diffusion test (ADT) was also performed.
      RESULTS: The effect of the composite resins on bacterial growth was minimal and
      limited to a few days only. One-week-aged composites promoted growth of S. mutans
      and A. viscosus. The antibacterial properties in direct contact were more potent
      than in planktonic bacterial growth. Amalgam showed complete inhibition of both
      bacteria in all phases, and the effect lasted for at least 1 week. The materials'
      elute had no effect on both bacterial growth with the exception of complete
      inhibition of S. mutans in amalgam. The later results correlated with the ADT.
      CONCLUSIONS: The present findings demonstrate potent and lasting antibacterial
      properties of amalgam, which are lacking in composite resins. This may explain
      the clinical observation of biofilm accumulated more on composites compared to
      amalgams. It follows that the assessment of antibacterial properties of poorly
      soluble materials has to employ more than one assay.

PMID- 16996675
TI  - Actinide speciation in relation to biological processes.
AB  - In case of accidental release of radionuclides into the environment, actinides
      represent a severe health risk to human beings following internal contamination
      (inhalation, ingestion or wound). For a better understanding of the actinide
      behaviour in man (in term of metabolism, retention, excretion) and in specific
      biological systems (organs, cells or biochemical pathways), it is of prime
      importance to have a good knowledge of the relevant actinide solution chemistry
      and biochemistry, in particular of the thermodynamic constants needed for
      computing actinide speciation. To a large extent, speciation governs
      bioavailability and toxicity of elements and has a significant impact on the
      mechanisms by which toxics accumulate in cell compartments and organs and by
      which elements are transferred and transported from cell to cell. From another
      viewpoint, speciation is the prerequisite for the design and success of potential
      decorporation therapies. The purpose of this review is to present the state of
      the art of actinide knowledge within biological media. It is also to discuss how
      actinide speciation can be determined or predicted and to highlight the areas
      where information is lacking with the aim to encourage new research efforts.

PMID- 16996676
TI  - Resource exploitation and cross-region growth trajectories: nonparametric
      estimates for Chile.
AB  - As a sector of primary concern for national development strategies, mining keeps
      stimulating an intensive debate in Chile, regarding its role for long-term
      growth. Partly drawn on theoretical contributions to growth and mineral resource
      accounting, this analysis assesses patterns of economic growth across Chilean
      regions. The theoretical and methodological rationale for focusing on weak
      sustainability, by testing convergence across regions in a distribution dynamics
      perspective, is first discussed. This is followed by a brief review of policy
      issues and previous empirical findings of concern to Chile's mining and regional
      growth. Panel data over the period 1960-2001 are analysed, with growth measured
      in terms of both income per capita as such, and sustainable measures of this
      variable. Kernel density and quantile regression estimates indicate persistent
      bimodal (if not possibly trimodal) distribution of nationally standardised
      regional incomes per capita, whereby conditions for cross-region convergence are
      matched only within the inner range of this distribution.

PMID- 16996677
TI  - Management of stage I testis cancer.
AB  - OBJECTIVE: Over the last 5 years the management of stage I testis cancer has
      changed tremendously. This review focuses on the latest changes in diagnostics
      and treatment of clinical stage I non-seminomatous and seminomatous germ cell
      tumors. METHODS: A non-structured literature search (MEDLINE) was performed,
      including recently published papers (up to March 2006) on the subject. RESULTS:
      Organ-sparing surgery has become an accepted approach to treat malignant and
      nonmalignant tumours in a solitary testis. With certain precautions and adjuvant
      radiotherapy, this approach has proven to be as effective as orchidectomy.
      Prognostic factors strongly influence the decision for or against adjuvant
      treatment in seminoma and non-seminoma. With the help of a risk-adapted approach,
      about 50% of patients with clinical stage I testis cancer will favour close
      surveillance instead of immediate adjuvant treatment. Several well-conducted
      trials have helped to substantiate the management. Surgical staging by
      retroperitoneal lymph node dissection became an exception. Patients with non
      seminoma with high risk for occult metastatic disease will favour adjuvant
      chemotherapy and in patients with seminoma radiotherapy with reduced dosage will
      be challenged by carboplatin monotherapy. CONCLUSION: With adequate diagnostics
      and treatment, 100% of patients with stage I testis cancer will survive. Future
      research will focus on quality control, adherence to guideline recommendations,
      and further reduction of treatment to diminish the risk of late sequalae for
      patients with adjuvant radiotherapy or chemotherapy.

PMID- 16996678
TI  - The origin of the bone scan as a tumour marker in prostate cancer.

PMID- 16996679
TI  - Efficacy of the InVance male sling in men with stress urinary incontinence.
AB  - OBJECTIVES: To evaluate the efficacy and safety of the InVance bulbourethral
      sling in male stress urinary incontinence. MATERIALS AND METHODS: Between June
      2003 and April 2005, the InVance bulbourethral sling was implanted into 50
      patients with urinary incontinence after prostate surgery in 49 cases and pelvic
      trauma in 1 case. The patients were monitored and evaluated in a prospective
      manner (continence, tolerance, and satisfaction). The treatment was considered to
      be successful if the patient stopped wearing any kind of continence pad (patient
      cured) or only one pad per day (patient improved), with no de novo urinary
      disorders and without significant postvoid residual urine. Patient satisfaction
      with the procedure was assessed. RESULTS: After a median follow-up of 6 mo, 50%
      of patients were dry, 26% had improved, and 24% suffered treatment failure. The
      success rates for the patients with severe incontinence and those who had
      undergone radiation therapy were 50% and 25%, respectively. All patients who were
      dry or had improved were satisfied and presented no obstructive or irritative de
      novo urinary disorders. The overall success rate for the 51 procedures conducted
      was 74.5%. Six cases of transitory acute urine retention and six cases of
      persistent perineal pain were reported. Explantation was necessary because of
      suppuration of the sling in three patients and of a de novo irritative urinary
      disorder in one patient. No cases of pubic osteitis or urethral erosion were
      reported. CONCLUSIONS: The InVance bulbourethral sling procedure makes it
      possible to treat stress urinary incontinence after prostate surgery with
      satisfactory and lasting short-term results. Severe incontinence and a past
      history of pelvic radiation therapy seem to be factors contributing to the
      failure of this procedure.

PMID- 16996680
TI  - Possible involvement of ATP-purinoceptor signalling in the intercellular
      synchronization of intracellular Ca2+ oscillation in cultured cardiac myocytes.
AB  - Isolated and cultured neonatal cardiac myocytes contract spontaneously and
      cyclically. The contraction rhythms of two isolated cardiac myocytes, each of
      which beats at different frequencies at first, become synchronized after the
      establishment of mutual contacts, suggesting that mutual entrainment occurs due
      to electrical and/or mechanical interactions between two myocytes. The
      intracellular concentration of free Ca(2+) also changes rhythmically in
      association with the rhythmic contraction of myocytes (Ca(2+) oscillation), and
      such a Ca(2+) oscillation was also synchronized among cultured cardiac myocytes.
      In this study, we investigated whether intercellular communication other than via
      gap junctions was involved in the intercellular synchronization of intracellular
      Ca(2+) oscillation in spontaneously beating cultured cardiac myocytes. Treatment
      with either blockers of gap junction channels or an un-coupler of E-C coupling
      did not affect the intercellular synchronization of Ca(2+) oscillation. In
      contrast, treatment with a blocker of P2 purinoceptors resulted in the
      asynchronization of Ca(2+) oscillatory rhythms among cardiac myocytes. The
      present study suggested that the extracellular ATP-purinoceptor system was
      responsible for the intercellular synchronization of Ca(2+) oscillation among
      cardiac myocytes.

PMID- 16996681
TI  - In vitro anti-tumour and cyto-selective effects of coumarin-3-carboxylic acid and
      three of its hydroxylated derivatives, along with their silver-based complexes,
      using human epithelial carcinoma cell lines.
AB  - The chemotherapeutic potential of coumarin-3-carboxylic acid (C-3-COOH) and a
      series of three hydroxylated coumarin-3-carboxylic acid ligands, namely 6-hydroxy
      coumarin-3-carboxylic acid (6-OH-C-3-COOH), 7-hydroxy-coumarin-3-carboxylic acid
      (7-OH-C-3-COOH) and 8-hydroxy-coumarin-3-carboxylic acid (8-OH-C-3-COOH), along
      with their corresponding silver-based complexes, namely 6-hydroxycoumarin-3
      carboxylatosilver (6-OH-C-COO-Ag), 7-hydroxycoumarin-3-carboxylatosilver (7-OH-C
      COO-Ag) and 8-hydroxycoumarin-3-carboxylatosilver (8-OH-C-COO-Ag), was determined
      using two human-derived carcinoma (A-498 and Hep-G2), along with two non
      carcinoma human-derived cell lines (CHANG and HK-2). All of the ligands and their
      silver complexes induced a concentration-dependent cytotoxic effect. Furthermore,
      hydroxylation of C-3-COOH and its subsequent complexation with silver led to the
      production of a series of compounds with dramatically enhanced cytotoxicity, with
      6-OH-C-3-COO-Ag having the greatest activity. Additionally, all of the metal
      based complexes were selectively cytotoxic to both carcinoma-derived cell lines,
      relative to normal renal and hepatic cells. In comparative studies with
      cisplatin, and based on the IC(50) values obtained with Hep-G2 cells, it appeared
      that the coumarin-silver complexes were between 2 and 5.5 times more cytotoxic
      than cisplatin. All of the coumarin-silver complexes inhibited DNA synthesis,
      which did not appear to be mediated through intercalation. Furthermore, results
      obtained from Ames tests showed that all of the test agents and their phase I
      metabolites were non-mutagenic. Taken together, these findings suggest that both
      hydroxylation particularly in the 6th position and complexation with silver,
      served to significantly augment the cytotoxic properties of C-3-COOH, to yield a
      compound which acts as a cyto-selective agent, as it is a significant killer of
      cancer, relative to normal cells. We suggest that this group of compounds may
      have a therapeutic role to play in the successful treatment and management of
      cancer in man.

PMID- 16996682
TI  - Inhibition of PAX2 expression results in alternate cell death pathways in
      prostate cancer cells differing in p53 status.
AB  - Inhibition of apoptosis is a critical pathophysiological factor that contributes
      to the development of prostate cancer. Recently, PAX2, a transcriptional
      regulator implicated in oncogenesis, has been demonstrated to be expressed by
      prostate cancer. However, its downstream molecular pathways for suppression of
      apoptosis, other than the tumor suppressor gene p53, have yet to be elucidated.
      Here, we examine the effects of inhibiting PAX2 expression by prostate cancer
      cells that differ in p53 gene status. These data collectively demonstrate that
      PAX2 inhibition results in cell death independent of p53, and that additional
      tumor suppressors or cell death pathways may be inhibited by PAX2 in prostate
      cancer cells.

PMID- 16996683
TI  - Association analysis of the paraoxonase-1 gene with Alzheimer's disease.
AB  - Genetic variants in the paraoxonase (PON) gene cluster, particularly a single C/T
      promoter polymorphism (rs 705381) in the PON-1 gene, have recently been
      associated with Alzheimer's disease (AD). The T allele, in particular, presents
      an increased risk for the development of AD. Here, we investigate the potential
      role of this polymorphism in an Italian case-control population consisting of 306
      sporadic AD patients and 275 controls, and also evaluate a possible interaction
      with the ApoE genotype. No association between the PON-1 polymorphism and AD was
      observed. The T allele frequency was slightly over-represented in AD patients
      compared to the controls, but this was far from being statistically significant.
      Our sample was evaluated to have 97.3% power to detect an OR of 2.0 (64.3% power
      with OR=1.5) at an alpha level of 0.05. No evidence of an interaction between the
      T risk-allele and the ApoE epsilon4 allele status and no effect of the PON-1
      polymorphism on age at onset was detected. Our results do not support other
      studies indicating that the PON-1 promoter polymorphism plays a major role in AD,
      suggesting that other large studies are necessary to further elucidate the effect
      of PON on the development of the disease in the general population.

PMID- 16996684
TI  - Voluntary exercise and clomipramine treatment elevate prepro-galanin mRNA levels
      in the locus coeruleus in rats.
AB  - Exercise exerts antidepressant effects in humans and rodent models of affective
      disorders. These effects may be mediated by the upregulation of endogenous
      factors that exert antidepressant actions. The physiological functions and
      behavioral actions of the neuropeptide galanin (GAL) suggest antidepressant
      activity. Previous studies have shown that various modes of exercise elevate GAL
      gene expression in the locus coeruleus (LC) in rats. The present experiments
      examined the interaction between voluntary exercise and antidepressant
      pharmacotherapy. Male Sprague-Dawley rats were provided access to activity wheels
      (exercise condition) or inoperative wheels (sedentary condition) for 28 days.
      Rats in each group were injected with clomipramine (10mg/kg/day) or vehicle
      throughout this period (for 3 weeks). Prepro-GAL mRNA in the LC was measured by
      in situ hybridization histochemistry. Exercise and clomipramine treatment
      significantly elevated GAL gene expression, though prepro-GAL mRNA levels in rats
      receiving both interventions did not differ from sedentary controls that received
      vehicle. Prepro-GAL mRNA levels were significantly correlated with running
      distance. The results further implicate a role for GAL in the antidepressant
      effects of exercise and pharmacotherapy, though the mechanisms through which
      these treatments influence GAL gene expression appear to differ significantly.

PMID- 16996685
TI  - Combination of adenoviral vector-mediated neurotrophin-3 gene transfer and
      retinoic acid promotes adult bone marrow cells to differentiate into neuronal
      phenotypes.
AB  - This study aims to investigate the effect of adenoviral vector-mediated
      neurotrophine-3 (NT-3) gene transfer and retinoic acid (RA) pretreatment on
      inducing neuronal differentiation of bone marrow mesenchymal stem cells (MSCs) in
      vitro. MSCs could be efficiently transduced by NT-3 gene via recombinant
      adenoviral vectors (Adv). Combination of AdvNT-3 and RA significantly promoted
      MSCs to differentiate into cell types associated with phenotypes of neural
      lineages, which included neural markers nestin, NF, MAP2 and PSD95 as detected by
      immunocytochemistry. But the expressions of GFAP in these cells were not obvious.
      RT-PCR analysis revealed that AdvNT-3 in combination with RA pretreatment could
      initiate the transcription of TrkC mRNA. These results demonstrate that the
      combination of AdvNT-3 and RA pretreatment may promote neuronal differentiation
      of MSCs, which may serve as ideal seed cells for the repair of spinal cord
      injury.

PMID- 16996686
TI  - Hypoxia-induced upregulation of endothelial small G protein RhoA and Rho
      kinase/ROCK2 inhibits eNOS expression.
AB  - The small G protein RhoA and its downstream effector Rho-kinase/ROCK2 play an
      important role in regulation of various vasculature cellular functions. Nitric
      oxide (NO) produced by endothelial NO synthase (eNOS) is an important mediator of
      vascular homeostasis and cerebral blood flow. Using the human endothelial cell
      line HUVEC, the present study investigated the role of RhoA and Rho-kinase in
      endothelial eNOS protein expression under hypoxic conditions as an in vitro model
      of ischemia. RhoA protein levels in HUVEC were low under normoxic conditions, but
      were significantly increased after 5h of hypoxia. Endothelial Rho-kinase
      expression was not detected until after 3h of hypoxia; such expression remained
      significantly increased after 5h. On the other hand, endothelial eNOS expression
      was similar after 3h of hypoxia, but was significantly decreased after 5h. The
      hypoxia-induced decrease in eNOS expression was significantly enhanced by
      expression of the constitutively active form of RhoA and significantly inhibited
      by suppression of RhoA expression by small interfering RNA. The hypoxia-induced
      decrease in eNOS expression was significantly inhibited when endogenous Rho
      kinase activation was inhibited by Rho-binding domain expression. Furthermore,
      the hypoxia-induced decrease in eNOS expression was significantly enhanced by
      expression of the constitutively active form of Rho-kinase. Since expression and
      activation of RhoA and Rho-kinase inhibit eNOS expression in endothelial cells,
      attempts to down-regulate RhoA and Rho-kinase by multiple drugs, such as statins
      or Rho-kinase inhibitors, might provide endothelial and cardiovascular benefits
      through upregulation of eNOS.

PMID- 16996687
TI  - Cortical acetylcholine esterase activity and ApoE4-genotype in Alzheimer disease.
AB  - Positron emission tomography (PET) studies have demonstrated reduced
      acetylcholine esterase (AChE) activity as an indicator of cholinergic impairment,
      which is a main pathogenic process in Alzheimer's disease (AD). The E4 allele of
      apolipoprotein epsilon (ApoE4) is a major risk factor for AD. We examined the
      relation between ApoE-genotype and cortical AChE activity. In 19 patients (mean
      age 64) with mild to moderate AD (mean MMSE 22) PET with C-11-labeled N-methyl-4
      piperidyl-acetate (MP4A) was performed and the ApoE4-genotype was determined.
      Parametric images of AChE hydrolysis were generated using a non-invasive
      technique and analysed globally and regionally. A neuropsychological battery
      testing memory, attention, executive functions, visuoconstruction, and language
      was administered. The mean cortical AChE activity was reduced significantly in
      both groups compared to reference values. The ApoE4 positive subjects (two
      homozygotes, nine heterozygotes) had significantly higher (p<0.05) AChE levels
      (MP4A hydrolysis rate 0.0753+/-0.0088min(-1)) than the ApoE4 negative subjects
      (n=8, 0.0654+/-0.0090min(-1)). Both groups were comparable with regard to age (63
      versus 65) and dementia severity (MMSE 20 versus MMSE 22). AChE-impairment
      correlated significantly with the word fluency task (r=0.041, p<0.05) in the
      ApoE4 negative group only. These results indicate that cortical AChE activity is
      relatively well preserved in ApoE4 carriers, either by preservation of its
      cellular expression or as AChE activity in amyloid plaques.

PMID- 16996688
TI  - Event related potentials reveal differences between morphological (prefixes) and
      phonological (syllables) processing of words.
AB  - Behavioral measures in visual priming tasks show opposite effects for syllables
      and morphemes, which indicate that they are processed by two independent systems.
      We used event related potentials (ERPs) to explore two priming situations in
      Spanish: prefix related words (reaccion-REFORMA [reaction-reform]), in which
      prime and target words shared a first syllable that was also a prefix, and
      syllable related words (regalo-REFORMA [gift-reform.]), in which the shared first
      syllable was a pseudoprefix in the prime word. Prefix related pairs, unlike
      syllable related pairs, evoked a very early positivity in reaction to the target
      (at 150-250ms window), suggesting that the prefix information is immediately
      available, at a prelexical stage. By contrast, syllable related pairs showed a
      larger N400 effect. This late negativity may be caused by lateral inhibition
      among lexical candidates activated in the lexicon by the prime's first syllable.

PMID- 16996689
TI  - Systematic review of observational (behavioral) measures of pain for children and
      adolescents aged 3 to 18 years.
AB  - Observational (behavioral) scales of pain for children aged 3 to 18 years were
      systematically reviewed to identify those recommended as outcome measures in
      clinical trials. This review was commissioned by the Pediatric Initiative on
      Methods, Measurement, and Pain Assessment in Clinical Trials (www.immpact.org).
      In an extensive literature search, 20 observational pain scales were identified
      for review including behavior checklists, behavior rating scales, and global
      rating scales. These scales varied in their reliance on time sampling and
      inclusion of physiological items, facial and postural items, as well as their
      inclusion of multiple dimensions of assessment (e.g., pain and distress). Each
      measure was evaluated based on its reported psychometric properties and clinical
      utility. Scales were judged to be indicated for use in specific acute pain
      contexts rather than for general use. Two scales were recommended for assessing
      pain intensity associated with medical procedures and other brief painful events.
      Two scales were recommended for post-operative pain assessment, one for use in
      hospital and the other at home. Another scale was recommended for use in critical
      care. Finally, two scales were recommended for assessing pain-related distress or
      fear. No observational measures were recommended for assessing chronic or
      recurrent pain because the overt behavioral signs of chronic pain tend to
      habituate or dissipate as time passes, making them difficult to observe reliably.
      In conclusion, no single observational measure is broadly recommended for pain
      assessment across all contexts. Directions for further research and scale
      development are offered.

PMID- 16996690
TI  - Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn
      neurons by peripheral inflammation contributes to heat hyperalgesia.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a unique member of the CDK family. It is
      predominantly expressed in postmitotic neurons and has been implicated in
      neuronal plasticity. The present study showed that Cdk5 and p35 were expressed in
      primary sensory and dorsal horn neurons, while p25, an N-terminal truncated
      derivative of p35, could only be detected in the dorsal horn neurons.
      Importantly, in the case of control rats, the p35 protein level was much higher
      in small- and medium-diameter DRG neurons than it was in large neurons. Following
      CFA injection, Cdk5 activity was upregulated in both primary sensory and dorsal
      horn neurons. Cdk5 activation in DRG neurons required p35, whereas p25 was
      required in the dorsal horn. Intrathecal pretreatment with Roscovitine, a
      specific inhibitor of Cdk5 activity, and intrathecal delivery of the DN
      Cdk5(N144) gene both alleviated CFA-induced heat hyperalgesia but not mechanical
      allodynia. In contrast, overexpression of Cdk5, p35 or p25 in primary sensory and
      dorsal horn neurons significantly enhanced heat hyperalgesia. We conclude that
      Cdk5/p35 and Cdk5/p25 complexes in primary sensory and dorsal horn neurons may
      potentially be involved in nociceptive transmission after inflammation and may be
      employed in synaptic plasticity underlying pain hypersensitization.

PMID- 16996691
TI  - Neutrophil infiltration is implicated in the sustained thermal hyperalgesic
      response evoked by allergen provocation in actively sensitized rats.
AB  - It has been proposed that allergen provocation induces hyperalgesia but the
      involvement of immunoglobulin E and leukocytes remains poorly understood. Here,
      we have compared the profile of allergen-evoked thermal hyperalgesic response in
      both passively and actively sensitized rats, and investigated the role of
      leukocytes in allergen-evoked nociception. Wistar rats were passively sensitized
      with an intraplantar injection of immunoglobulin E anti-dinitrophenylated bovine
      serum albumin monoclonal antibody (0.5 microg/paw), and challenged with
      dinitrophenylated bovine serum albumin (0.5 microg/paw) 24 h later.
      Alternatively, the animals were actively sensitized with a mixture of Al(OH)3 and
      ovalbumin and challenged intraplantarly with ovalbumin (12 microg/paw) 14 days
      later. We found that the thermal hyperalgesic responses set in very rapidly and
      with comparable intensity in both passively and actively sensitized rats.
      However, while in the former group the response was shorter, peaking within 1 h
      and reducing thereafter, a marked plateau was observed from 1 to 6 h post
      challenge in the latter group. Actively sensitized rats also had higher
      neutrophil influx in the plantar tissue, as attested by both myeloperoxidase
      activity and histological analysis. Treatment of actively sensitized rats with
      either fucoidin (10 mg/kg, i.v) or anti-rat neutrophil antiserum (i.p.) reduced
      neutrophil accumulation and the late hyperalgesic response noted from 3 to 6 h
      post-challenge. Thus, we conclude that though immunoglobulin E-mediated
      mechanisms can cause thermal hyperalgesia, components of the cellular immune
      reaction are crucial in order to amplify and sustain the immediate hyperalgesic
      response triggered by allergen, in a process dependent on neutrophil recruitment.

PMID- 16996692
TI  - An outbreak of East Coast Fever on the Comoros: a consequence of the import of
      immunised cattle from Tanzania?
AB  - In 2003 and 2004, a severe epidemic decimated the cattle population on Grand
      Comore, the largest island of the Union of Comoros. Fatalities started soon after
      the import of cattle from Tanzania. Theileria parva and its vector, Rhipicephalus
      appendiculatus, could be identified as the main culprits of the epidemic.
      Characterisation by multilocus genotyping revealed that the T. parva parasites
      isolated on the Comoros were identical to the components of the Muguga cocktail
      vaccine used in Tanzania to immunise cattle. Therefore, it is believed that East
      Coast Fever reached the Comoros while some of the imported livestock got infected
      in Tanzania by ticks of which the immature stadia fed on Muguga cocktail
      vaccinated animals. Since the Comorian government neither has the financial means
      nor the competent staff to pursue an adequate epidemiosurveillance, the danger
      exists that without external assistance and in a context of continuing
      globalisation more transboundary diseases will affect the Comorian livestock
      sector in the future.

PMID- 16996693
TI  - A combinatorial approach to substrate discrimination in the P450 CYP1A subfamily.
AB  - A comparison of all known mammalian CYP1A sequences identifies nineteen sequence
      regions that are conserved within all 1A1s or within all 1A2s but at the same
      time systematically differ between any 1A1 and any 1A2. The purpose of this study
      was to explore links between these specific CYP1A sequence signatures and
      substrate specificity shift through the kinetic analysis of combinatorial
      variants of increasing complexity. The less complex variants correspond to
      multiple mutations within a short segment of their sequence. The more complex
      variants correspond to mosaic P450s recombining 1A1 and 1A2 sequences (up to 5
      crossovers per sequence). Fifty-eight such functional CYP1A variants and parental
      wild-type enzymes were expressed in yeast and assayed with 7-alkoxyresorufins and
      ethoxyflurorescein ethyl ester as substrates. Observed kinetic data were analyzed
      by multivariate statistical analyses and hierarchical clustering in order to
      highlight correlations and identify potential sequence-activity relationships
      within the three-dimensional function space investigated. Several variants are
      outliers in these representations and show a redistribution of their substrate
      specificity compared to wild-type CYP1As. Some combinations of sequence elements
      were identified that significantly discriminate between 1A1 and 1A2 for these
      three substrates. The comparison of this combinatorial approach with previous
      results of site-directed mutagenesis is discussed.

PMID- 16996694
TI  - An ascorbate-reducible cytochrome b561 is localized in macrophage lysosomes.
AB  - Cytochromes b561 (Cyts b561) are a family of intrinsic membrane proteins involved
      in ascorbate-mediated transmembrane electron transport. The chromaffin granule
      Cyt b561 (CGCytb) is believed to transport electrons donated by extravesicular
      ascorbate (ASC) across the membrane to intravesicular monodehydroascorbate (MDA)
      supporting catecholamine synthesis in neuroendocrine tissues. Another isoform,
      the duodenal Cyt b561 (Dcytb), was reported to have ferric reductase activity,
      possibly facilitating intestinal iron uptake. Herein, a new Cyt b561 homologue,
      LCytb (for lysosomal Cytb561) was found expressed in the late endosomal-lysosomal
      membrane. LCytb shared high sequence similarity with CGCytb (45% identity) and
      Dcytb (42% identity). Moreover, four heme-coordinating His residues, and putative
      ASC and MDA binding sites were highly conserved. Recombinant LCytb exhibited an
      ASC-reducible b-type Cyt absorbance spectrum with alpha-band maximum at 561 nm in
      the spectrum of the reduced protein. Northern blots and Western blots revealed
      that LCytb was predominantly expressed in lung, spleen, thymus, testis and
      placenta. In situ hybridization and immunofluorescence studies further
      demonstrated that the protein was expressed in the alveolar macrophages of the
      lung, in the white pulp of the spleen, widespread in the thymus, and in the
      Sertoli cells of the testis. Sequence analysis indicated the presence of a
      (DE)XXXL(LI)-type signal in the C-terminal of the protein, predicting a late
      endosomal-lysosomal subcellular localization. This localization was confirmed by
      double labeling experiments in RAW264.7 and 293 cells, stably transfected with
      LCytb.

PMID- 16996695
TI  - Variants of synesthesia interact in cognitive tasks: evidence for implicit
      associations and late connectivity in cross-talk theories.
AB  - This study examines the interaction between two types of synesthesia: ordinal
      linguistic personification (OLP; the involuntary association of animate qualities
      such as gender/personality to linguistic units such as letters/numbers/days) and
      grapheme-color synesthesia (the involuntary association of colors to letters
      and/or numbers). By examining both variants in the same individual we aim to: (a)
      show that features of different synesthetic variants interact in cognitive tasks,
      (b) provide a cognitive model of this interaction, and (c) constrain models of
      the underlying neurological roots of this connectivity. Studies have shown
      inhibition in Stroop-type tasks for naming font colors that clash with
      synesthetic colors (e.g. slower naming of green font for synesthetically red
      letters). We show that Stroop-type slow-down occurs only when incongruent colors
      come from other letters with matching (but not mis-matching) gender (experiment
      2). We also measure the speed of OLP gender judgments (e.g. a=female; experiment
      1) and show that response times are slowed by incongruent colors from other
      letters with mis-matching (but not matching) genders. Our studies suggest that
      synesthetic variants interact and that their concurrents can become implicitly
      connected without mediation from inducing stimuli. We interpret these findings in
      light of recent developmental data showing protracted heterochronous neuronal
      development in humans, which continues through adolescence in parietal, frontal
      and perisylvian areas.

PMID- 16996697
TI  - Typologies of alcohol use disorders among men with schizophrenic disorders.
AB  - Alcohol use disorders are common among persons with schizophrenia and are
      associated with a vast array of negative consequences: criminality, poor
      compliance with treatment, and reoccurrence of acute episodes of psychosis. In
      samples of non-mentally disordered individuals, typologies of alcohol use
      disorders have been shown to be useful in furthering understanding of etiology
      and of effective treatments. Such typologies, however, have not previously been
      examined in individuals with schizophrenia. The main objective of the study was
      to validate four uni-dimensional typologies and the multi-dimensional Type I/II
      Type A/B typology in a sample of men with schizophrenic disorders and alcohol use
      disorders. All uni-dimensional typologies showed at least some degree of
      concurrent validity. The Type I/II-Type A/B typology was successfully replicated
      with fair concurrent validity across the domains of pre-morbid risk factors and
      drug use, but not for the domains of criminality, illness, or personality. The
      predictive validity was poor for all typologies. The results provide evidence for
      the heterogeneity of alcohol use disorders among men with schizophrenia.

PMID- 16996698
TI  - Chaos theory and the treatment of refractory status epilepticus: Who benefits
      from prolonged anesthesia, and is there a better way?
AB  - Refractory status epilepticus (SE) is a condition of continuous seizure activity
      in which there is a regular, rapid, succession of spike discharges in the brain.
      It is incompatible with normal consciousness and is associated with an extremely
      high morbidity and mortality. Prior to 1990, prevailing opinion held that a brief
      period of anesthesia (up to two weeks) was to be recommended, but that if SE
      persisted this was a sign of irreversible brain damage. Therefore support of the
      patient in SE was not recommended beyond two weeks. On the basis of the
      theoretical constructs of chaos theory we hypothesized that, for selected cases,
      anesthesia should be continued indefinitely until the SE resolved. This became
      the standard of care at the University of Washington and at other institutions.
      After several years, the accumulating evidence lends support for this hypothesis
      and we are now able to propose which patients will benefit from such therapy. It
      is hypothesized that only those patients for whom there is no underlying brain
      disease, beyond epilepsy, are likely to benefit. Secondly, chaos theory suggests
      that a strong perturbation will cause a rapid transition from the stable
      attractor of SE to the stable attractor representing normal consciousness. In
      certain ways, SE is analogous to ventricular tachycardia, where the cardiac
      muscle has an abnormally fast rhythm incompatible with proper cardiac function.
      Therefore the second hypothesis is that a brain perturbation, analogous to
      defibrillation, may be even more useful than anesthesia in refractory SE.

PMID- 16996696
TI  - Bacterial artificial chromosome transgenic analysis of dynamic expression
      patterns of regulator of G-protein signaling 4 during development. I. Cerebral
      cortex.
AB  - Signaling through G-protein-coupled receptors is modulated by a family of
      regulator of G protein signaling (RGS) proteins that have been implicated in
      several neurological and psychiatric disorders. Defining the detailed expression
      patterns and developmental regulation of RGS proteins has been hampered by an
      absence of antibodies useful for mapping. We have utilized bacterial artificial
      chromosome (BAC) methods to create transgenic mice that express GFP under the
      control of endogenous regulator of G-protein signaling 4 (RGS4) enhancer
      elements. This report focuses on expression patterns in the developing and mature
      cerebral cortex. Based on reporter distribution, RGS4 is expressed by birth in
      neurons across all cortical domains, but in different patterns that suggest
      region- and layer-specific regulation. Peak expression typically occurs before
      puberty, with complex down-regulation by adulthood. Deep and superficial neurons,
      in particular, vary in their patterns across developmental age and region and, in
      primary sensory cortices, layer IV neurons exhibit low or no expression of the
      GFP reporter. These data suggest that altering RGS4 function will produce a
      complex neuronal phenotype with cell- and subdomain-specificity in the cerebral
      cortex.

PMID- 16996699
TI  - Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the
      treatment of attention-deficit hyperactivity disorder and Rett syndrome.
AB  - Psychostimulants, such as methylphenidate, are currently the most common used
      drug therapy for children with attention-deficit hyperactivity disorder (ADHD).
      However, a number of patients with ADHD either fail to respond to these drugs or
      experience side effects that preclude their use. The heptapeptide Semax is an
      analogue of the N-terminal fragment (4-10) of adrenocorticotropic hormone, but is
      completely devoid of any hormonal activity. It has been found to stimulate memory
      and attention in rodents and humans after intranasal application. Evidence from
      animal studies revealed that Semax can augment the effects of psychostimulants on
      central dopamine release and also stimulates central brain-derived neurotrophic
      factor (BDNF) synthesis. In addition, Semax could improve selective attention and
      modulate brain development. Since ADHD is likely to be a neurodevelopmental
      disorder with disturbance in dopamine and BDNF function, it is proposed in this
      paper that Semax may have good therapeutic potential in ADHD. Furthermore,
      increased BDNF activity is found to improve Rett syndrome, a severe
      neurodevelopmental disorder which is, in the majority of cases, caused by
      mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2). The
      potential therapeutic effect of Semax in Rett syndrome by increasing central BDNF
      activity may be of interest for further exploration in animal models of Rett
      syndrome.

PMID- 16996700
TI  - Evolutionary pathways of an ancient gene recX.
AB  - RecX is a regulator of RecA activity by interacting with RecA protein or RecA
      filaments. Genes encoding RecX were found in genomes of a wide diversity of
      bacteria and some plants (e.g., Arabidopsis thaliana and Oryza sativa). Our
      comparative genome analysis showed that although members of the RecX family are
      found in many bacterial species, they are not found in archaea and the only gene
      found in eukaryotes is likely derived from bacteria genomes. It is therefore
      proposed that RecX is of bacterial origin, and the gene had presented in the
      common ancestor of bacteria. Moreover, bacterial RecX and plant RecX domain are
      homologues, and RecX domain in plants may have derived from bacteria via unknown
      pathways. Plant RecX-like protein was formed by a gene fusion event between a
      unique N-terminal domain of unknown origin and RecX domain within plant cells.
      Finally, three possible evolutionary pathways from bacteria to plant were
      discussed.

PMID- 16996701
TI  - The complete mitochondrial genome of the whiting, Merlangius merlangus and the
      haddock, Melanogrammus aeglefinus: a detailed genomic comparison among closely
      related species of the Gadidae family.
AB  - We determined the first complete mitochondrial DNA (mtDNA) sequences for the
      whiting (Merlangius merlangus, family Gadidae, order Gadiformes) and the haddock
      (Melanogrammus aeglefinus, family Gadidae, order Gadiformes). The entire
      mitogenomes were amplified and sequenced by primer walking using newly designed
      specific internal primers. Lengths were 16,569 and 16,585 bases for whiting and
      haddock respectively, lengths which lie within the range of previously reported
      gadiform sequences from Atlantic cod (Gadus morhua, 16,696 bases) and walleye
      pollock (Theragra chalcogramma, 16,570 bases). Gene arrangement in both species
      conformed to the order seen in most vertebrate mitochondrial genomes. We
      identified a long intergenic spacer located between the tRNA(Thr) and tRNA(Pro)
      genes (of 100 and 70 bp long for whiting and haddock, respectively), as
      previously described for other species of the order Gadiformes. Using nucleotide
      and amino acid divergence data of four complete gadoid mitogenomes (M.
      merlangius, M. aeglefinus, G. morhua and T. chalcogramma), we examined in detail
      the relative mtDNA mutation patterns across genes and among Gadidae species and
      tested for the performance of each protein-coding, transfer RNA and ribosomal RNA
      gene in depicting the expected phylogeny among the four species, as compared with
      the whole genome dataset. This comparison may be particularly useful in
      phylogenetic analyses of such a diverse fish family, as well as for the
      understanding of the patterns of nucleotide substitution of the mtDNA at low
      levels of divergence.

PMID- 16996703
TI  - Sampling and repeatability of radiometric faecal culture in bovine Johne's
      disease.
AB  - The repeatability of detection of Mycobacterium avium subsp. paratuberculosis
      (Map) within and between samplings from 16 paratuberculous dairy cows (13
      subclinical; 3 clinical) was investigated by radiometric culture of quadrants of
      faecal dung pats collected on four to seven occasions over a 10-16-day period.
      Results were compared to serological status and to pathological and
      bacteriological findings in multiple tissues obtained at slaughter from 15 of the
      animals 2-6 weeks after the faecal samplings. From faecal samples taken on 77
      occasions over the 2-week period, 296/308 (96%) quadrants were culture positive,
      with samples from all cattle showing evidence of faecal shedding of Map.
      Histological lesions typical of paratuberculosis were present in 14 of the 15
      cows examined at slaughter, varying in severity from mild (two animals) to
      moderate (4) and advanced (8), and all predilection tissue sites yielded Map. The
      negative faecal samples were derived from a single animal that was culture
      positive in two quadrants on each of the first two (of four) sampling occasions
      (i.e. culture positive in only 4 of 16 collected quadrants). This animal was
      found to be histologically negative at slaughter, and culture positive from three
      of five predilection tissue sites. Faecal samples from cows with subclinical and
      clinical paratuberculosis, with lesion severity ranging from mild to severe at
      multiple predilection sites, produced faeces with relatively consistent
      concentrations of Map within samples. There was significant variation in
      concentrations of Map between samples in individual animals over a period of 2
      weeks, but this did not affect the dichotomous positive-negative culture status
      for 15 of the 16 cattle. A faecal sample collected non-randomly per rectum thus
      provides a representative specimen for detection of Map by radiometric culture on
      a single sampling occasion.

PMID- 16996702
TI  - Genomic organization and allelic expression of UBE3A in chicken.
AB  - UBE3A, the gene associated with Angelman syndrome, is part of a cluster of genes
      in the human chromosome 15q11-q13/mouse chromosome 7C region, that is subject to
      genomic imprinting. In human and mouse brain, UBE3A is expressed predominantly
      from the maternal allele, and the paternal allele is silenced. A current model
      concerning the evolution of genomic imprinting, the parental conflict hypothesis,
      posits that this epigenetic phenomenon is restricted to eutherian mammals. It has
      been recently reported, however, that several chicken orthologues of mammalian
      imprinted loci display DNA replication asynchrony, a property of imprinted genes.
      A separate group also reported monoallelic expression of chicken IGF2 in
      developing chicken embryos. These observations could suggest that genomic
      imprinting may occur in chicken. We have assembled the predicted mRNA consensus
      sequence for the chicken UBE3A gene using published ESTs. We report a high degree
      of homology with the human UBE3A at the nucleotide and protein levels, as well as
      a highly conserved genomic organization. Biallelic expression of UBE3A is
      observed in embryonic chicken brain and limb, indicating that UBE3A is not
      subject to genomic imprinting in chicken.

PMID- 16996704
TI  - Optimizing rumen functions in the close-up transition period and early lactation
      to drive dry matter intake and energy balance in cows.
AB  - The large deficit in energy intake in relation to energy requirements during the
      transition and early lactation periods means that high-producing cows need energy
      dense rations. High-starch diets are intensively fermented by the microbial
      ecosystem in the rumen, giving rise to a high production of VFAs and resulting in
      a drop in pH and the accumulation of lactic acid, which exacerbates the decline
      in pH and is considered as the major cause of rumen acidosis. This rumen
      dysfunction affects rumen microbes and results in less efficient digestion,
      thereby decreasing feed intake and exacerbating the energy deficit in the cows.
      The main way to limit the risk of acidosis is by diet management. Thus, animals
      must be progressively adapted to grain ingredients during the 3-week period
      before calving. Furthermore, the diet management strategy will be to privilege
      low-degradable starch and include enough fiber in the diet to stimulate
      rumination and salivation. Chemical additives can be used to prevent rumen
      acidosis. Rumen pH can be controlled by direct addition of chemical buffers at
      doses of 1-2% of DM intake. Metabolic hydrogen can be mobilized through specific
      metabolic pathways such as propionogenesis to compete with the synthesis of
      lactic acid. This can be achieved by adding propionate precursors such as
      aspartate, malate or fumarate. However, these additives are not economically
      viable, and will not easily be accepted by consumers. Probiotics, which are
      mainly supplied as live yeasts, have to be regarded as a solution for preventing
      subacute acidosis but they are not considered as an efficient cure for acute
      acidosis. Although the mechanisms of action of probiotics are not fully
      understood, this paper proposes a plausible model of their mode of action.
      Recently, additives based on plant extracts have been proposed as a solution for
      optimizing rumen functions, but further efficacy studies and safety trials are
      required before these additives can be marketed. The addition of fibrolytic
      enzymes has been suggested to improve the digestion of the dietary fiber fraction
      during acidosis. Although the results obtained so far are encouraging, more
      ruminant-specific research needs to be carried out on these enzymes. Some
      antibiotics are potential inhibitors of Gram-positive bacteria, which are
      involved in rumen acidosis, but their use as feed additives has been banned from
      01/01/2006 in the EU.

PMID- 16996705
TI  - The effect of nutritional management of the dairy cow on reproductive efficiency.
AB  - The cause of low fertility in dairy cows is multifactorial. Poor nutrition during
      the dry and early postpartum periods results in reduced glucose, insulin, insulin
      like growth factor (IGF-I) and low LH pulse frequency with concomitant increases
      in beta-hydroxy butyrate, non-esterified fatty acids (NEFA) and triacylglycerol.
      Cows must mobilize large lipid, but also some protein reserves, with a consequent
      increased incidence of such metabolic disorders as hypocalcaemia, acidosis,
      ketosis, fatty liver and displaced abomasums. The occurrence of milk fever and
      ketosis affects uterine contractions, delays calving and increases the risk of
      retained foetal membranes (RFM) and endometritis. The nutritional risk factors
      that cause RFM are hypocalcaemia, high body condition score (BCS) at calving and
      deficiencies in Vitamin E and selenium. The risk factors for endometritis are
      hypocalcaemia, RFM, high triacylglycerol and NEFA. Thus, metabolic disorders
      predispose cows to gynaecological disorders, thereby reducing reproductive
      efficiency. Cows that are overconditioned at calving or those that lose excess
      body weight are more likely to have a prolonged interval to first oestrus,
      thereby prolonging days open. Nutritionally induced postpartum anoestrus is
      characterized by turnover of dominant follicles incapable of producing sufficient
      oestradiol to induce ovulation due to reduced LH pulse frequency. High nutrition
      can also increase metabolic clearance rate of steroid hormones such as
      progesterone or oestradiol. Lower concentrations of oestradiol on the day of
      oestrus are highly correlated with the occurrence of suboestrus, thereby making
      the detection of oestrus in high yielding cows even more difficult. Nutrition
      also affects conception rate (CR) to AI. Cows that develop hypocalcaemia,
      ketosis, acidosis or displaced abomasums have lower CRs and take longer to become
      pregnant. Excessive loss of BCS and excess protein content of the ration can
      reduce CR while supplemental fats that attenuate the production of F2alpha can
      improve CR. The increased metabolic clearance rate of progesterone (P4), which
      decreases blood concentrations during early embryo cleavage up to the blastocyst
      stage is associated with decreased CRs. In conclusion, poor nutritional
      management of the dairy cow, particularly before and after calving, is a key
      driver of infertility.

PMID- 16996706
TI  - Novel poloxamer-based nanoemulsions to enhance the intestinal absorption of
      active compounds.
AB  - On the basis of Pluronic P104 as primary emulsifier and Lauroglycol 90 as
      amphiphilic oil phase, two nanoemulsion systems were developed with Pluronic((R))
      L62 or L81 as secondary emulsifiers. The possible nanoemulsion region of
      combinations of these excipients was described in ternary phase diagrams. Three
      formulations were selected from the nanoemulsion region and their potential
      impact on oral absorption was examined in the Caco-2 monolayer model of the small
      intestine. The apparent permeability of the BCS class III compound Atenolol was
      enhanced 2.5-fold, of BCS class II compound Danazol 3.2-fold and of BCS class I
      compound Metoprolol 1.4-fold. The three formulations were very well tolerated by
      the Caco-2 cells, which was confirmed by TEER measurements, a MTT test and a LDH
      release test.

PMID- 16996707
TI  - Evaluation of ibuprofen-loaded microspheres prepared from novel copolyesters.
AB  - The utility of two novel linear random copolyesters to encapsulate and control
      the release of ibuprofen, via microspheres, was investigated. Various
      manufacturing parameters, including temperature, disperse phase volume and
      polymer:ibuprofen ratios were altered during the microsphere production. The
      effects of these changes on the morphological characteristics of the
      microspheres, yield, drug loading, encapsulation efficiency and drug release
      rates were examined. The diameter of the microspheres ranged from 36 to 89 microm
      and showed both smooth and ridged surfaces. Microsphere diameter was probably
      determined by the internal phase volume, while surface morphology was controlled
      by manufacturing temperature. Greater encapsulation efficiency was obtained by
      increasing the polymer:ibuprofen ratio and by reducing the internal phase volume.
      For all batches there was an initial burst drug release into phosphate buffer (pH
      7.4) over the first 2-4h, which was followed by a much slower release rate over
      the remaining time period. Drug release rates during both these phases were
      dependent upon the amount and nature of the polymer in the microspheres, noting
      that the more hydrophilic polymer provided faster release rates. Ibuprofen
      solubility appeared to play a dominant role in controlling release, although both
      encapsulation efficiency and microsphere morphology were also contributing
      factors.

PMID- 16996708
TI  - Evaluation of the physical stability of two oleogels.
AB  - Oleogels are semisolid systems obtained with an organogelator and a hydrophobic
      liquid that have been investigated over the past few years and that could play an
      important role as dermatological bases. Recently, we have developed an oleogel of
      sorbitan monostearate (19wt.%) and sweet almond oil (SM-SAO) and another one of
      cholesterol (3.5wt.%) and liquid paraffin (Ch-LP). The aim of this work is to
      access their physical stability using three different methodologies. The gels
      were stored at different temperatures (20 and 40 degrees C) over a 3-month
      period. Appearance and textural properties were assessed on each month. An
      accelerated test was also performed where the temperature changed between 4 and
      40 degrees C every 24h, during 7 days. Rheological tests were also carried out as
      they could provide useful elements to predict stability. The gels were quite
      stable at 20 degrees C, being the SM-SAO gel the most stable. The textural
      properties of both gels were influenced by temperature. The decrease of the
      textural parameters, observed after storage at 40 degrees C and in the cycling
      test, was more significant for the SM-SAO gel. A good correlation was found
      between rheological analysis and conventional stability tests. The
      heating/cooling cycle test provided useful information in a short period of time.

PMID- 16996709
TI  - Characterization of chondroitin sulfate and its interpenetrating polymer network
      hydrogels for sustained-drug release.
AB  - The goal of this work was to utilize the chondroitin sulfate (CS) based hydrogels
      for a drug delivery matrix. CS is a good structure/disease-modifying anti
      osteroarthritis drug (S/DMOAD). However, the readily water-soluble nature limits
      its application as a solid-state drug-delivery vehicle. In this study, two
      methods were used to prepare CS hydrogels: directly crosslinking CS with
      poly(ethylene glycol) diglycidyl ether (EX-810) abbreviated as CS-EX or forming
      an interpenetrating polymer network named CS-EX-IPN. The CS-EX-IPN hydrogel was
      carried out by sequentially crosslinking reaction between CS and EX-810 in one
      phase and acrylic acid and di(ethylene glycol) diacrylate (DEGDA) as a counter
      phase. The swelling percent, cross-section morphology, and effective crosslinking
      density of hydrogels were characterized. The values of compression modulus and
      effective crosslinking density of CS-EX-IPN were approximately 3.6-fold higher
      than CS-EX. We also characterized the release of a model drug, diclofenac sodium
      (DS) and a model protein, bovine serum albumin (BSA), from CS-EX and CS-EX-IPN.
      The similar release profiles of DS were observed in the both hydrogels but slower
      release rate of BSA occurred in CS-EX-IPN. The release profiles of the two model
      drugs fit in a diffusion-controlled mechanism. The D(eff) values are in the order
      of 10(-5) for DS and 10(-7) for BSA.

PMID- 16996710
TI  - Idiopathic hypereosinophilic syndrome complicated by central sinovenous
      thrombosis.
AB  - Idiopathic hypereosinophilic syndrome (IHES) is a rare disorder affecting
      cardiac, pulmonary and nervous systems with peripheral neuropathy, encephalopathy
      and cerebral thromboembolism. We report a 7-year-old boy with IHES who developed
      central sinovenous thrombosis and cerebral hemorrhage. Although he had
      hypereosinophilia for more than 6 months, he was asymptomatic until the sudden
      onset of vomiting and headache due to superior sagittal sinus thrombosis.
      Molecular analysis in peripheral blood did not reveal any mutation in the Fip1
      like-platelet-derived growth factor receptor alpha chain (FIP1L1-PDGFRA) gene
      which was recently reported to be mutated in IHES. Since there must be symptoms
      or signs of organ involvement to fulfill the IHES criteria, we could not make a
      diagnosis of IHES until the onset of central nervous system involvement. We
      suggest that anti-coagulant therapy should be considered for asymptomatic
      patients with hypereosinophilia because hypereosinophilia may induce thrombosis
      in various organs.

PMID- 16996711
TI  - Neuropathology of developmental abnormalities.
AB  - Varieties of neuropathological disorders are caused by a perturbation of normal
      developmental processes, resulting from insults by heterogeneous etiologic
      factors. These factors trigger the sequence of molecular, biochemical, and
      morphologic alterations of the brain, resulting morphologically and/or
      functionally abnormal brain. The resulting brain contains basic components of the
      normal brain but is assembled in an abnormal way. The developmental stage when
      the insults occur appears to largely dictate the outcome of the pathological
      processes. Depending on the developmental stage involved, the morphology of the
      brain may be grossly abnormal or is apparently normal but functionally abnormal.
      The brain development progresses in an orderly fashion and can be divided into
      several major developmental stages; the neurulation (neural tube formation),
      ventral induction (formation of prosencephalon), neuroepithelial cell
      proliferation and migration, neuroglial differentiation and establishment of
      neuronal circuits. The perturbation of these developmental stages results in
      uniquely specific pathological outcome, regardless of the etiologic
      factors/agents. In this review, I will briefly discuss the normal pattern of
      brain development and neuropathology of the representative disorders resulting
      from the deviation of normal developmental processes in the individual
      developmental stage.

PMID- 16996712
TI  - Vertebral artery origin stenting with buddy wire technique in tortuous subclavian
      artery.
AB  - Catheterization of vessels with severe tortuosity and atherosclerotic changes may
      represent a technical challenge and is associated with a higher incidence of
      vascular complications [Putman CM, Chaloupka JC. Use of large-caliber coronary
      guiding catheters for neurointerventional applications. AJNR Am J Neuroradiol
      1996;17:697-704]. Placement of guiding catheter to the tortuous subclavian artery
      in vertebral artery origin stenting procedure is such a condition with
      difficulties. In the presence of severe tortuosity of aortic arch and proximal
      subclavian artery placement of guiding catheter may be difficult and yield poor
      backup support. We describe a technique that uses a buddy wire to make the
      guiding catheter stable in its proper position and make possible to perform
      stenting the vertebral artery origin stenosis.

PMID- 16996713
TI  - Francisella tularensis LVS grown in macrophages has reduced ability to stimulate
      the secretion of inflammatory cytokines by macrophages in vitro.
AB  - The virulence of Francisella tularensis LVS is determined in part by its ability
      to invade and replicate within macrophages and stimulate the production of
      inflammatory cytokines. The present study determined the effects of growing F.
      tularensis in macrophages on its ability to stimulate cytokine secretion by
      macrophages. F. tularensis grown in Mueller-Hinton broth (FtB) stimulated the
      secretion of large amounts of TNF-alpha, IL-12p40, IL-6 and MCP-1/CCL2 when
      incubated with macrophages overnight. In contrast, F. tularensis released from
      infected macrophages (FtMac) stimulated very little secretion of these cytokines
      by primary cultures of murine peritoneal macrophages, human monocytes or
      macrophage cell lines. Stimulation of nitric oxide production by FtMac was also
      less than that elicited by FtB. FtMac killed with gentamicin or paraformaldehyde
      also stimulated low levels of cytokine secretion. FtMac recovered the ability to
      stimulate cytokine secretion after overnight culture in broth. Infection of
      macrophages with FtMac inhibited the cytokine response to subsequent stimulation
      with LPS from Escherichia coli but did not affect Fcgamma receptor-mediated
      phagocytosis. FtMac were ingested by macrophages at about half the rate of FtB,
      however, this did not account for the lower cytokine secretion. FtMac and FtB
      replicated at similar rates within macrophages. Finally, Mice infected with FtMac
      had a higher mortality rate than those infected with FtB. These results reveal
      that growth in macrophages causes a reversible phenotypic change in F. tularensis
      that is associated with decreased stimulation of cytokine secretion, inhibition
      of LPS-stimulated secretion of inflammatory cytokines by macrophages and
      increased lethality in mice.

PMID- 16996714
TI  - New insights into gene positional clustering and its properties supported by
      large-scale analysis of various differentiation pathways.
AB  - To understand how genes are distributed on chromosomes we bring new insights into
      gene positional clustering and its properties. We have made a large-scale
      analysis of three types of differentiation and we observed that genes that
      subsequently enter into different cell processes are positionally clustered on
      chromosomes. Genes from the clusters are transcribed subsequently with respect to
      time kinetics and also to position. This means that the genes related to a
      cellular process are clustered together, independent of the period of time during
      which they are active and important for the process. Our results also demonstrate
      not only that there are general regions of increased or decreased levels of gene
      expression, but also that, in fact, in some chromosome regions we can find
      clustering of genes related to specific cell processes. The results provided in
      this paper also support the theory of "transcription factories" and show that
      transcription of genes from the clusters is managed by softer epigenetic
      mechanisms.

PMID- 16996715
TI  - A global view of twenty years of Brain, Behavior, and Immunity.

PMID- 16996716
TI  - Organization of brain extracellular matrix in the Chilean fat-tailed mouse
      opossum Thylamys elegans (Waterhouse, 1839).
AB  - We investigated the structural and molecular organization of the extracellular
      matrix in Thylamys elegans, a marsupial representative of the mammalian order
      Didelphimorphia. Perineuronal nets (PNs) associated with distinct types of
      neurons were visualized by detection of chondroitin sulfate proteoglycans and
      hyaluronan, and by labeling with Wisteria floribunda agglutinin (WFA), a marker
      for PNs in the mammalian brain. In the neocortex of Thylamys, these methods
      revealed PNs on pyramidal cells. In contrast, parvalbumin-immunoreactive
      interneurons in the neocortex and hippocampal formation (displaying robust, WFA
      labeled PNs in placental mammals) were ensheathed only with a delicate rim of
      hyaluronan and proteoglycans not detectable with WFA. The absence of WFA staining
      was characteristic also of some subcortical regions which contained PNs intensely
      labeled for chondroitin sulfate proteoglycan and hyaluronan. However,
      corresponding to placental mammals, numerous subcortical nuclei showed clearly
      WFA-stained PNs. Similar as in placental mammals, cholinergic basal forebrain
      neurons and tyrosine hydroxylase-immunoreactive neurons of the substantia nigra
      and locus coeruleus were devoid of PNs. Together with our earlier study on
      Monodelphis, the present results reveal that South American opossums show either
      a particular "marsupial" or "Didelphid" type of extracellular matrix
      chemoarchitecture, supporting the view that these components may vary
      phylogenetically as integral parts of neuronal physiology at the systems and
      single cell level.

PMID- 16996717
TI  - Neural correlates of verbal semantic memory in patients with temporal lobe
      epilepsy.
AB  - Functional imaging data suggest that the core network engaged in verbal semantic
      memory (SM) processing encompasses frontal and temporal lobe structures, with a
      strong left lateralization in normal right handers. The impact of long term
      temporal lobe epilepsy (TLE) on this network has only partly been elucidated. We
      studied verbal SM in 50 patients with chronic, intractable TLE (left TLE=26,
      right TLE=24) and 35 right handed normal controls using a verbal fMRI semantic
      decision paradigm. All patients had language lateralized to the left hemisphere,
      as verified by the intracarotid amobarbital procedure. Within and between group
      analyses showed remarkable, group-specific activation profiles. The control group
      activated frontal and temporal areas bilaterally, with a strong left
      predominance. Left TLE patients showed a shift of activations of left frontal and
      medial temporal areas to homologous regions in the right hemisphere. Furthermore,
      left TLE subjects utilized subcortical structures such as the thalamus and
      putamen to accomplish the verbal SM task. Contrastively, the activation pattern
      of right TLE patients resembled that of normal controls, but exhibited
      "hypofrontality" with a shift from frontal to posterior regions in the temporal,
      parietal and occipital lobe. Our results show that chronic epileptic activity
      originating from temporal seizure foci is associated with an alteration of neural
      circuits which support semantic language processing and that side of seizure
      focus has a specific impact on the resulting activation network. These findings
      presumably result from morphological changes and from functional reorganization
      which are both inherent to chronic TLE.

PMID- 16996718
TI  - Valproic acid and chromatin remodeling in schizophrenia and bipolar disorder:
      preliminary results from a clinical population.
AB  - Levels of acetylated Histone 3 and 4 proteins are strongly predictive of a
      chromatin structure that is conducive to gene expression. In cell and animal
      studies, valproic acid is a potent inhibitor of histone deactylating enzymes, and
      consequently results in increased levels of acetylated Histone 3 (acH3) and
      acetylated Histone 4 proteins (acH4). To examine this effect in a clinical
      setting, 14 schizophrenic and bipolar patients were treated with valproic acid
      (Depakote ER), either as monotherapy or in combination with antipsychotics, over
      a period of 4 weeks. AcH3 and acH4 levels from lymphocyte nuclear protein
      extracts were measured by Western Blot. Treatment with Depakote ER resulted in a
      significant increase of acH3 and a trend-level increase of acH4. Levels of
      valproic acid were positively and significantly correlated with percent increase
      in acH3 but not acH4. Schizophrenia patients were significantly less likely to
      increase their acH3 and acH4 levels after 4 weeks on Depakote ER. The authors
      consider these results in the context of future application of HDAC inhibitors to
      the treatment of psychiatric disorders.

PMID- 16996719
TI  - The University of California Performance Skills Assessment (UPSA) in
      schizophrenia.
AB  - This study evaluated the University of California Performance-based Skills
      Assessment (UPSA) in a Canadian outpatient schizophrenia setting. The UPSA was
      administered to 64 patients with schizophrenia and schizoaffective disorder and
      to 42 nonpsychiatric controls. Patient and control samples did not differ in age,
      gender composition, first language or country of birth. Patients demonstrated
      significantly lower performance than healthy participants on 3 of 5 UPSA
      subscales as well as on a summary index. Moreover, performance varied
      significantly with patients' support requirements in the community. In contrast,
      the Household Management and Transportation subscales yielded non-significant
      group differences and failed to correlate with community support requirements.
      Examination of score distributions raised the possibility of a ceiling effect
      that limited the discriminating power of UPSA subscales, thus imposing
      qualifications on clinical interpretations of this instrument. Performance-based
      assessment of life skills provides an important new perspective on functional
      outcome in schizophrenia and serious mental illness. However, psychometric
      properties, task difficulty and the nature of different mental health settings,
      populations and communities must be considered in the design and application of
      these instruments.

PMID- 16996720
TI  - Molecular and diagnostic aspects of genetic skin fragility.
AB  - Genetic syndromes with skin fragility represent a heterogeneous group of very
      rare disorders caused by mutations in genes encoding proteins or protein subunits
      important for the mechanical resistance of keratinocytes and for cell-cell or
      cell-extracellular matrix adhesion. The common symptoms are skin blistering or
      peeling, with various degrees of severity and distribution, ranging from
      localized to generalized forms. Associated features include involvement of skin
      annexes, mucous membranes, teeth, muscles or the digestive tract. Morphological
      investigation of skin samples provides evidence for the tissue level of blister
      formation, while immunostainings may reveal defective proteins, providing clues
      concerning the genetic origin of the disease. Extensive mutation analysis and
      subsequent identification of new gene defects provide accurate diagnostics, and
      lead to better understanding of the functions of the respective proteins, with
      the potential for new therapeutic strategies.

PMID- 16996721
TI  - MYG1, novel melanocyte related gene, has elevated expression in vitiligo.

PMID- 16996722
TI  - Association study between the dopamine receptor D(4) gene and obsessive
      compulsive disorder.
AB  - Pharmacological and neuroanatomical evidence suggest the involvement of the
      dopaminergic system in obsessive-compulsive disorder (OCD). Analysis of the 48-bp
      dopamine receptor D(4) (DRD4) gene polymorphism in a sample of 210 OCD patients
      and 202 healthy control subjects showed a significant association (chi(2)=27.5,
      df=6, p=0.0003). This difference was attributable to a lower frequency of allele
      4R in OCD patients compared with the control group (chi(2)=9.33, p=0.0027).
      However, we did not replicate previous findings of an association between the 7R
      allele and OCD patients with tics. Finally, we analyzed a sub-sample of 86 OCD
      families. E-TDT analysis in 70 informative parents did not confirm the
      association observed in our case-control analysis. In conclusion, the current
      study cannot exclude an association between DRD4 gene and OCD in the largest
      sample analyzed. However, further studies will be required to confirm if the DRD4
      gene is involved in the pathogenesis of this disorder.

PMID- 16996723
TI  - Thioperamide reduces intracellular calcium in mouse brain synaptosomes.
AB  - Intracellular calcium regulation is vital for cells, especially for neurons;
      raised levels are associated with cytotoxicity and neuronal death. In this
      report, we present the first experimental evidence showing a concentration
      dependent reduction of free calcium in the mouse brain synaptosomes by
      thioperamide (THP), an H3 receptor antagonist. This is interesting in view of the
      recent reports on the anticonvulsant and cognition facilitating effects of THP. A
      neuroprotective potential of THP is suggested.

PMID- 16996724
TI  - Evaluation of glycosaminoglycans content and 5-hydroxytryptamine 2B receptor in
      the heart valves of Sprague-Dawley rats with spontaneous mitral valvulopathy--a
      possible exacerbation by dl-amphetamine sulfate in Fischer 344 rats?
AB  - Spontaneous valvulopathy has been described as nodular or segmental thickenings
      composed of fibromyxoid tissue in the subendocardium of various valve-leaflets in
      aging rats, but its pathogenesis and significance are incompletely understood. In
      this study, we examined the 5-hydroxytryptamine 2B receptor (5HT2BR) expression
      and characterization of extracellular matrix (ECM) components, and related these
      to the presence of valvulopathy in the mitral valve-leaflet (spontaneous mitral
      valvulopathy, SMV) of Sprague-Dawley (SD) rats. We also examined hearts from
      Fischer 344 (F344) rats treated with dl-amphetamine sulfate for 103 weeks to
      further explore the potential for drug-induced exacerbation of SMV. In SD rats,
      valve-leaflets with SMV exhibited a greater valve thickness, a higher amount of
      glycosaminoglycans, a lower amount of collagen and increased number of 5HT2BR
      positive cells. Our data on morphology and ECM changes showed a striking
      similarity between SMV in SD rats and anorexigen-associated valvulopathy in
      humans, and increased 5HT2BR-positive cells in SMV implies that 5HT2BR may play a
      role in pathogenesis. Further, increased incidence and severity of SMV in F344
      rats by treatment with dl-amphetamine suggest that a drug-induced exacerbation of
      SMV may exist in rats. However, additional research is needed to confirm a role
      for 5HT2BR in the pathogenesis of SMV in SD rats, and to further characterize the
      relationship between dl-amphetamine treatment and exacerbation of SMV in F344
      rats.

PMID- 16996726
TI  - Pyrolysis of mixtures of sewage sludge and manure: a comparison of the results
      obtained in the laboratory (semi-pilot) and in a pilot plant.
AB  - A pilot-scale pyrolysis process was carried out for the treatment of a mixture of
      two types of waste, sewage sludge and cattle manure, comparing the results with
      others obtained under laboratory conditions (semi-pilot scale). The aim of this
      study was to obtain the energetic valorization of the products. Owing to the
      specific characteristics of the plant, two products were obtained from the
      process: gas and carbonized solid. As no liquid fraction was obtained, the gas
      fraction is a greater percentage made up of both condensable and non-condensable
      compounds, which were obtained separately at the laboratory scale. The pilot
      plant was designed so that the gases produced by thermolysis were burnt
      continuously in a combustion chamber, while the carbonized fraction was fed in
      batches for co-combustion. To determine composition and combustion ability, the
      gas and solid products from the pilot process were characterized by
      chromatographic analysis of the gaseous fraction and chemical analysis and
      programmed-temperature combustion of the carbonized solid. The composition of the
      combustion gases, rich in light hydrocarbons, and the carbon present in the
      carbonized fraction enable the energetic valorization of these products. The
      combustion gases were subjected to a cleaning process and their composition
      analysed twice: before and after the gas cleaning treatment. The study led to a
      positive assessment of the possible use of the process products as fuel, provided
      that the combustion gases are treated. As most of the sulphur and chlorine from
      the original waste are mainly concentrated in the solid fraction, the use of char
      as a fuel will depend on the effectiveness of clean-up techniques for combustion
      gases. During gas cleansing, neutralizing with sodium bicarbonate proved
      effective, especially for the acidic compounds HCl, HF and SO(2).

PMID- 16996725
TI  - The lysyl hydroxylase isoforms are widely expressed during mouse embryogenesis,
      but obtain tissue- and cell-specific patterns in the adult.
AB  - Lysyl hydroxylase catalyzes the hydroxylation of lysine residues in collagenous
      sequences. Three isoforms (LH1, LH2 and LH3) of lysyl hydroxylase have been
      characterized, and LH2 is present as two alternatively spliced forms. In order to
      better understand the functional differences between the isoforms in vivo, the
      expression of the different isoforms was studied in mouse embryos and adult
      tissues. Our data indicate a widespread expression of all isoforms during
      embryogenesis, whereas the expression profiles become more specialized in adult
      tissues. The expression of LH2 was more tissue-specific, whereas a uniform and
      housekeeping like behavior was observed for LH3. Some cells express both LH2 and
      LH3, while a clear cell specificity was seen in some tissues. Moreover,
      immunoelectron microscopy revealed differences in the localization of LH2 and
      LH3. LH2 was localized intracellularly in the ER in all tissues studied, whereas
      the localization of LH3 was either intracellular or extracellular or both,
      depending on the tissue. Furthermore, our data indicate that the alternative
      splicing of LH2 is developmentally regulated. The short form of LH2 (LH2a) is the
      predominant form until E11.5; the long form (LH2b) dominates thereafter and is
      the major form in many adult tissues. Interestingly, however, adult mouse kidney
      and testis express exclusively the short form, LH2a. The results reveal a
      specific regulation for the expression of LH isoforms as well as for alternative
      splicing of LH2 during embryogenesis and in different tissues.

PMID- 16996727
TI  - Effect of composted sewage sludge application to soil on sweet pepper crop
      (Capsicum annuum var. annuum) grown under two exploitation regimes.
AB  - The aim of this study is to monitor the effect of the application of three
      increasing amounts of composted sewage sludge (3, 6 and 9 kg compost m(-2)) on
      the physico-chemical properties of a horticultural calcareous soil where sweet
      pepper plants (Capsicum annuum var. annuum) cv. California were grown. A
      comparative study of two different exploitation regimes was carried out; the
      first was an open-air field-grown plot and the second plot was kept under
      controlled conditions in a greenhouse. Changes in physical and chemical
      properties measured in soil and sweet pepper crop were recorded during crop
      growth in order to measure the evolution of these properties as a consequence of
      increasing compost applications. Organic matter, total nitrogen Kjeldahl and
      available phosphorus contents increased in soil after composted sewage sludge
      applications. The 9 kg compost m(-2) application promoted the appearance of
      deleterious effects on the properties of soil, such as salt accumulation, a
      significant increase in the electrical conductivity and an input of heavy metals
      (Pb>Cr>Cd). The 6 kg compost m(-2) application provided a supply of nutrients
      necessary to grow peppers plants under both exploitation regimes. Pepper fruit
      biomass production under greenhouse was almost 60% higher compared to that of the
      open-air plot. Lower contents of Ca and increased levels of Cu in fruit under
      greenhouse growing conditions compared to those of open-air grown peppers seemed
      to promote the occurrence of blossom-end rot, affecting more than 10% of the
      harvested fruits.

PMID- 16996728
TI  - Effect of inoculation in composting processes: modifications in lignocellulosic
      fraction.
AB  - Three microbial isolates, identified as Bacillus shackletonni, Streptomyces
      thermovulgaris and Ureibacillus thermosphaericus were tested as inoculants in
      composting processes in relation to their capacity to improve lignocellulose
      degradation. Different wastes from agricultural activities were used as raw
      material for the heaps: pepper plant waste (PPW) as the main component and olive
      oil mill waste (OMW), almond shell (AS), pruning waste (PW) and rice straw (RS)
      as additives. Cellulose was more extensively degraded than hemicellulose and
      lignin, although the use of inoculants (B. shackletonni and S. thermovulgaris)
      improved the action of the autochthonous microbiota just in the AS heaps. A
      higher efficiency was observed for lignin, since lower concentrations of this
      polymer were detected in the inoculated heaps in relation to control heaps. U.
      thermosphaericus was the most efficient microorganism since inoculation with this
      strain decreased the final lignin content in a range between 17.23% and 24.34%.
      S. thermovulgaris and B. shackletonni led to a higher reduction of the lignin
      levels in the OMW and PW heaps (14.25% and 19.07% less lignin than control heaps)
      and OMW (13%), respectively. The composting process can therefore be improved by
      means of inoculation if the microorganisms used for this purpose are appropriate
      for the characteristics of the raw material.

PMID- 16996729
TI  - A DNA biosensor based on peptide nucleic acids on gold surfaces.
AB  - We present a DNA biosensor based on self-assembled monolayers (SAMs) of thiol
      derivatized peptide nucleic acid (PNA) molecules adsorbed on gold surfaces.
      Previous works have shown that PNA molecules at an optimal concentration can be
      self-assembled with their molecular axes normal to the surface. In such
      structural configuration BioSAMs of PNAs maintain their capability for
      recognizing complementary DNA. We describe the combined use of PM-RAIRS and
      synchrotron radiation XPS for the detection and spectroscopic characterization of
      PNA-DNA hybridization process on gold surfaces. RAIRS and XPS are powerful
      techniques for surface characterization and molecular detection, which do not
      require a fluorescence labeling of the target. We present a characterization of
      the spectroscopic IR and XPS features, some of them associated to the phosphate
      groups of the DNA backbone, as an unambiguous signature of the PNA-DNA
      heteroduplex formation. The N(1s) XPS core level peak after DNA hybridization is
      decomposed in curves components, and every component assigned to different
      chemical species. Therefore, the results obtained by means of two complementary
      structural characterization techniques encourage the use of PNA-based biosensors
      for the detection of DNA molecules on natural samples.

PMID- 16996730
TI  - Bioluminescence-based bioassays for rapid detection of nisin in food.
AB  - We have developed a method for determining ultralow amounts of nisin in food
      samples that is based on luminescent biosensor bacteria. Modified bacterial
      luciferase operon luxABCDE was placed under control of the nisin-inducible nisA
      promoter in plasmid pNZ8048, and the construct was transformed into Lactococcus
      lactis strains NZ9800 and NZ9000. The nisRK genes of these strains allow them to
      sense nisin and relay the signal to initiate transcription from nisA promoter.
      The resulting luminescence can be directly measured from living bacteria without
      the addition of exogenous substrates. Induction leads to detectable luminescence
      within ten minutes. Lyophilization of the biosensor cells produced viable and
      inducible sensor elements that can be utilized as freshly cultivated cells for
      rapid detection of nisin. The linear dose-response relationship perceived in the
      assay facilitates quantification of nisin in samples. The sensitivity of the
      nisin bioassay was 0.1 pg/ml in pure solution and 3 pg/ml in milk, exceeding the
      performance of all previously reported methods.

PMID- 16996731
TI  - Virtual imprinting as a tool to design efficient MIPs for photosynthesis
      inhibiting herbicides.
AB  - Molecular modelling and computational screening were used to identify functional
      monomers capable of interacting with several different photosynthesis-inhibiting
      herbicides. The process involved the design of a virtual library of molecular
      models of functional monomers containing polymerizable residues and residues able
      to interact with the template through electrostatic, hydrophobic, Van der Waals
      forces and dipole-dipole interactions. Each of the entries in the virtual library
      was probed for its possible interactions with molecular models of the template
      molecules. It was anticipated that the monomers giving the highest binding score
      would represent good candidates for the preparation of affinity polymers. Strong
      interactions were computationally determined between acidic functional monomers
      like methacrylic acid (MAA) or itaconic acid (IA) with triazines, and between
      vinylimidazole with bentazone and bromoxynil. Nevertheless, weaker interactions
      were seen with phenylureas. The corresponding blank polymers were prepared using
      the selected monomers and tested in the solid phase extraction (SPE) of
      herbicides from chloroform solutions. A good correlation was found between the
      binding score of the monomers and the affinities of the corresponding polymers.
      The use of computationally designed blanks can potentially eliminate the need for
      molecular imprinting, (adding a template to the monomer mixture to create
      specific binding sites). Data also showed that some monomers have a natural
      selectivity for some herbicides, which can be further enhanced by imprinting.
      Thus, in regard to retention on the blank polymer, we can estimate if the
      resulting imprinted polymer will be effective or not.

PMID- 16996732
TI  - Histopathological prognostic factors in medulloblastoma: high expression of
      survivin is related to unfavourable outcome.
AB  - Standard postoperative treatment of medulloblastoma consists of craniospinal
      irradiation and chemotherapy. Currently, only clinical factors are used for
      therapy stratification. To optimise treatment and patient outcome, biological
      prognostic markers are needed. In the present study we tested the prognostic
      influence of four histopathological parameters considered in recent publications
      as prognostic factors in medulloblastoma. We analysed a series of 82 Austrian
      medulloblastoma patients who were treated according to the consecutive HIT
      protocols for medulloblastoma conducted by the German Society of Paediatric
      Haematology and Oncology. Histological subtype and immunohistochemical expression
      of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue
      and correlated with patient outcome. Statistical analysis showed a significant
      correlation of high expression levels of survivin with decreased survival. None
      of the other investigated histopathological factors correlated significantly with
      patient outcome. Our data indicate that high survivin expression is related to
      unfavourable clinical outcome in medulloblastoma patients.

PMID- 16996733
TI  - In silico modeling of protein tyrosine phosphatase 1B inhibitors with cellular
      activity.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a potential drug target for the
      treatment of Type 2 diabetes and obesity. The design of PTP1B inhibitors as
      therapeutic agents has been hampered mostly owing to their poor cell permeability
      and oral bioavailability. In the present study, we investigated the cellular
      activity of PTP1B inhibitors in relation to the 3D structure using classical
      VolSurf analysis. A model based on the VolSurf descriptors for a set of 80
      compounds of PTP1B inhibitors, half of which display cellular activity, was
      analyzed using the principal components analysis (PCA) approach. The PCA model
      was applied to predict the cellular activities of an external data set of 40
      PTP1B inhibitors and satisfactory results were obtained. Further partial least
      squares (PLS) analysis revealed useful information about the behavior of the
      Volsurf descriptors in predicting the cell permeability and pharmacokinetic
      properties of PTP1B inhibitors. In silico ADME studies provide a valuable tool in
      the development of effective PTP1B inhibitors as drug candidates.

PMID- 16996734
TI  - Adamantane 11-beta-HSD-1 inhibitors: Application of an isocyanide multicomponent
      reaction.
AB  - A series of potent and selective adamantane aminoamide 11-beta-HSD-1 inhibitors
      has been optimized. Chemically these studies were expedited by utilizing readily
      obtained amino acids as starting materials or an isocyanide multicomponent
      reaction. Structure-activity relationship studies resulted in the discovery of
      dual human and mouse 11-beta-HSD-1 potent and selective inhibitors like
      adamantane 11 and related compounds with high metabolic stability and robust
      pharmacokinetic profiles.

PMID- 16996736
TI  - Synthesis and study of anti-inflammatory activity of some novel cyclophane
      amides.
AB  - Macrocyclic di- and tetra-amides with thia- and oxylinkages were synthesized and
      screened for in vitro anti-inflammatory activity. Cyclophane diamide 15 showed a
      dose-dependent activity, while the other cyclophane amides 16-20 exhibited mild
      activity.

PMID- 16996735
TI  - Design, synthesis, and anti-inflammatory activity both in vitro and in vivo of
      new betulinic acid analogues having an enone functionality in ring A.
AB  - Fifteen new betulinic acid analogues were designed, synthesized, and tested for
      anti-inflammatory activity. Many of these analogues effectively suppress nitric
      oxide (NO) production in RAW cells stimulated with interferon-gamma. Analogue 10
      is highly and orally active in vivo for induction of the anti-inflammatory and
      cytoprotective enzyme, heme oxygenase-1.

PMID- 16996737
TI  - A CLOCK-less clock.
AB  - Mammalian physiology is governed by a complex circadian timing system that
      involves interacting positive and negative transcriptional feedback loops. A key
      role in this feedback loop was attributed to the PAS domain helix-loop-helix
      protein CLOCK, on the basis of a dominant-negative mutation in this transcription
      factor. However, recent experiments by Reppert and coworkers with Clock knockout
      mice suggest that CLOCK is dispensable for rhythmic gene expression and behavior,
      presumably because other proteins can substitute for CLOCK in these animals.

PMID- 16996738
TI  - Multiple sclerosis: an infectious syndrome involving Chlamydophila pneumoniae.
AB  - The concept of autoimmune myelinopathy as the primary pathology in multiple
      sclerosis (MS) is problematic. Vasculitis is seen in the MS brain, both within
      lesions and in adjacent normal-appearing white matter. The first observation in
      acute relapse is the sudden, orderly death of oligodendrocytes; inflammatory
      removal of unsupported myelin seems to be a secondary process. An alternative
      explanation for these findings is that oligodendrocyte infection might trigger an
      inflammatory response. Many pathogens, including Chlamydophila (Chlamydia)
      pneumoniae, have been associated with MS. MS might be an infectious syndrome in
      which C. pneumoniae has a role in a subset of patients. Mechanisms by which such
      a cryptic infection could engender relapsing-remitting and, ultimately,
      progressive disease patterns are discussed.

PMID- 16996739
TI  - The capsular dynamics of Cryptococcus neoformans.
AB  - Cryptococcus neoformans is a soil-dwelling fungus that causes life-threatening
      illness in immunocompromised individuals and latently infects many healthy
      individuals. C. neoformans, unlike other human pathogenic fungi, is surrounded by
      a polysaccharide capsule that is essential for survival and enables C. neoformans
      to thwart the mammalian immune system. The capsule is a dynamic structure that
      undergoes changes in size and rearranges during budding. Here, the latest
      information and unresolved questions regarding capsule synthesis, structure,
      assembly, growth and rearrangements are discussed along with the concept that
      self-assembly is important in capsular dynamics.

PMID- 16996740
TI  - Effector-triggered immunity by the plant pathogen Phytophthora.
AB  - A new genetic locus mediating avirulence in the potato late blight pathogen
      Phytophthora infestans has been discovered. The Avr3b-Avr10-Avr11 locus is
      recognized by three different potato resistance genes, and is different from
      other Avr loci that have been identified thus far. This locus encodes a large
      protein with a WD40 domain and sequence similarities to transcription factors.
      Multiple, truncated copies of this gene have arisen by gene amplification and are
      characteristic of avirulent strains of P. infestans. Here, we describe the new
      avirulence locus and discuss the importance of this finding.

PMID- 16996741
TI  - Synthesis of neplanocin F analogues as potential antiviral agents.
AB  - Neplanocin F is a natural carbocyclic nucleoside. Herein, we describe the
      synthesis and antiviral activity of (+/-)-5'-deoxy-neplanocin F analogues. The
      key intermediate 4, synthesized from the commercially available (+/-)-2
      azabicyclo[2.2.1]-hept-5-en-3-one (ABH), was utilized to prepare the target
      nucleosides. Among the target compounds, 5'-deoxyneplanocin F adenine exhibited
      moderate anti-HIV activity in human lymphocytes without any marked cytotoxicity.

PMID- 16996742
TI  - Design, synthesis, and evaluation of a novel series of alpha-substituted
      phenylpropanoic acid derivatives as human peroxisome proliferator-activated
      receptor (PPAR) alpha/delta dual agonists for the treatment of metabolic
      syndrome.
AB  - A series of alpha-alkyl-substituted phenylpropanoic acids was prepared as dual
      agonists of peroxisome proliferator-activated receptors alpha and delta
      (PPARalpha/delta). Structure-activity relationship studies indicated that the
      shape of the linking group and the shape of the substituent at the distal benzene
      ring play key roles in determining the potency and the selectivity of PPAR
      subtype transactivation. Structure-activity relationships among the amide series
      (10) and the reversed amide series (13) are similar, but not identical,
      especially in the case of the compounds bearing a bulky hydrophobic substituent
      at the distal benzene ring, indicating that the hydrophobic tail part of the
      molecules in these two series binds at somewhat different positions in the large
      binding pocket of PPAR. alpha-Alkyl-substituted phenylpropanoic acids of (S)
      configuration were identified as potent human PPARalpha/delta dual agonists.
      Representative compounds exhibited marked nuclear receptor selectivity for
      PPARalpha and PPARdelta. Subtype-selective PPAR activation was also examined by
      analysis of the mRNA expression of PPAR-regulated genes.

PMID- 16996743
TI  - A model of the early mineralization process of mantle dentin.
AB  - The aim of this study was to investigate the relationship between proteoglycans
      (PGs) and collagen fibrils at the early mineralization process of mantle dentin.
      Ten first molar dental germs of rats were removed and fixed in
      glutaraldehyde/formaldehyde in cacodylate buffer and post-fixed in osmium
      tetroxide. The samples were dehydrated and embedded in epoxy resin. Ultrathin
      sections were contrasted and analyzed in TEM before and after treatment with
      EDTA, chondroitinases AC and ABC. After EDTA treatment, a electrondense substance
      associated with collagen fibril was removed, and did not stain again. A high
      magnification of these areas showed globular structures with 15 nm diameter
      surrounding collagen fibrils. In advanced mineralization areas, collagen fibrils
      showed a banded pattern and at high magnification the fibrils presented a light
      10 nm ring inside and a dark 10 nm ring outside. After chondroitinase treatment,
      the electrondense substance associated with collagen fibrils was removed, showing
      a banded pattern of clear and dark areas along them. From morphological data, the
      authors proposed a model of interaction between PGs and collagen fibrils, where
      glicosaminoglycans chains are inside the fibrils, while the protein core remains
      outside. That stereochemical arrangement would start the crystal nucleation.

PMID- 16996744
TI  - Experimental determination of calibration settings of a commercially available
      radionuclide calibrator for various clinical measurement geometries and
      radionuclides.
AB  - Following the approach of the National Primary Laboratory of the UK (NPL) for the
      calibration of radionuclide calibrators, but using a commercially available
      instrument with no data available in the literature, the radionuclide calibrator
      response was investigated as a function of different measurement geometries at
      the "Regina Elena" National Cancer Institute (IRE) in Rome. Working with Italian
      National Metrology Institute for ionising radiation quantities (ENEA-INMRI),
      specific calibration factors with traceability to national primary standards were
      determined for different types of glass vials, solid capsules and plastic
      syringes, investigating three radionuclides with different energy spectra (Tc
      99m, In-111, I-131). For each kind of syringe, calibration correction factors for
      different filling volumes were calculated. For Tc-99m and I-131 the difference
      between measured and true activity was in the range 2-7%, depending on
      measurement geometry. For In-111 a large percentage deviation from the true
      activity value was found in each geometry considered, reaching 35%. The magnitude
      of this difference is particularly dependent on the energies of the emitted
      photons.

PMID- 16996745
TI  - Bcl-2 enhances neurogenesis and inhibits apoptosis of newborn neurons in adult
      rat brain following a transient middle cerebral artery occlusion.
AB  - To determine whether Bcl-2 could influence adult neurogenesis and prevent
      apoptosis of newborn neurons, we injected Bcl-2 expressing plasmid into the
      lateral ventricle of rat brain immediately following a 30-min occlusion of the
      middle cerebral artery (MCAO). We found that Bcl-2 increased neural progenitor
      cells (BrdU+-DCX+) in the ipsilateral striatum, newborn immature neurons (BrdU+
      Tuj-1+) and newborn mature neurons (BrdU+-MAP-2+) in the ipsilateral striatum and
      frontal cortex at 1 to 4 weeks following MCAO. Bcl-2 overexpression promoted
      development of newborn neurons into GABAergic and cholinergic neurons in the
      ipsilateral striatum. Moreover, Bcl-2 significantly decreased the apoptosis of
      newborn neurons, determined by double staining of Tuj-1 and activated caspase-3
      (Tuj-1+-Casp+). These results indicate that overexpression of Bcl-2 in adult rat
      brain enhances neurogenesis and survival of newborn neurons. Increasing
      neurogenesis and preventing the death of newborn neuron may be a strategy to aid
      in the repair of adult brain after stroke.

PMID- 16996746
TI  - Role of pre-operative lymphangiogram and lympangioscintigraphy in the surgical
      management of spontaneous chylothorax.

PMID- 16996747
TI  - Reduced myocardial expression of calcium handling protein in patients with severe
      chronic mitral regurgitation.
AB  - OBJECTIVE: Left ventricle (LV) function was shown to be a principal determinant
      of morbidity and mortality in both uncorrected and surgically corrected mitral
      regurgitation (MR). However, the cellular mechanisms that develop in the LV
      remodeling secondary to volume overload in chronic severe MR is still not well
      defined. In single ventricular myocyte, a reduced contraction and slowed
      relaxation have been mainly attributed to defective intracellular Ca2+ currents.
      Between several Ca2+ handling proteins, sarcoplasmic reticulum Ca2+-ATPase 2
      (SERCA2) expression and activity determines not only the extent and rate of
      relaxation, but also the rate and amplitude of contraction. The aim of the study
      was to determine whether modifications of SERCA2 gene expression occurs in LV
      wall remodeling process secondary to chronic severe MR. METHODS: The LV samples
      were obtained from 12 patients presented LV wall remodeling (LV:
      diastolic/systolic diameter-70+/-7 mm vs 46+/-10 mm; diastolic/systolic volume
      260+/-65 ml vs 102+/-68 ml) due to chronic, severe MR. Expressions of SERCA2
      isoforms-SERCA2a and 2b mRNAs were estimated by semiquantitative RT-PCR and
      normalized to GAPDH. The protein levels of SERCA2 were determined by Western blot
      after normalization to actin. Results were compared with samples from non-failing
      human hearts (NFH). RESULTS: On SERCA2 mRNA levels, important reduction on both
      SERCA isoforms SERCA2a (-40%) and SERCA2b (-49%) compared to NFH, together with
      significant correlation between isoforms (r = 0.89; p = 0.01) were observed.
      SERCA2 protein levels were decreased (-38%) in MR compared to NFH. Also
      significant correlations between SERCA2a/2b and SERCA2 protein expression (r =
      0.83, p = 0.017; r = 0.68, p = 0.05, respectively) were observed. Moreover, a
      negative correlation between protein levels of SERCA2 (r = -0.64, p = 0.053) and
      left ventricular diastolic diameter was observed. CONCLUSIONS: In chronic volume
      overload the down-regulation of SERCA2a and 2b at the mRNA and SERCA2 protein
      levels exist. Moreover, protein levels of SERCA2 tend to correlate to the grade
      of left ventricular diastolic dilatation and suggest an important role LV
      remodeling.

PMID- 16996748
TI  - The different facets of protein kinases C: old and new players in neuronal signal
      transduction pathways.
AB  - Signal transduction pathways are crucial for cell-to-cell communication. Various
      molecular cascades allow the translation of distinct stimuli, targeting the cell,
      into a language that the cell itself is able to understand, thus elaborating
      specific responses. Within this context, a strategic role is played by protein
      kinases which catalyze the phosphorylation of specific substrates. The
      serine/threonine protein kinase C (PKC) enzymes family (at least 10 isoforms) is
      implicated in the transduction of signals coupled to receptor-mediated hydrolysis
      of membrane phospholipids. Within this molecular pathway, protein-protein
      interactions play a critical role in directing the distinct activated PKCs
      towards selective subcellular compartments, in order to guarantee spatio-temporal
      and localized cellular responses. A space-specific modulation of biochemical
      events is particularly important during learning. Among the various mechanisms,
      the modulation of mRNA decay appears to be an efficient post-transcriptional way
      of controlling gene expression during learning, allowing changes to take place in
      selected neuronal regions, in particular at synaptic level. To this regard,
      recent studies have pointed out that PKC activation is also involved in a novel
      signalling cascade leading to the stabilization of specific mRNAs. This review
      will especially focus the attention on the implication of PKC in memory trace
      formation and how alterations within this molecular cascade may have consequences
      on physiological and pathological neuronal aging (i.e. Alzheimer's disease).

PMID- 16996749
TI  - Structural correlates of intellectual impairment and autistic features in
      adolescents.
AB  - Intellectual disability, a common but under-researched condition, is strongly
      associated with autism spectrum disorders (ASD). Although studies have
      investigated the neural correlates of intelligence quotient (IQ) and ASD in
      intellectually unimpaired subjects, these issues have not been addressed in
      intellectually impaired subjects. We studied 63 intellectually disabled
      adolescents receiving additional learning support and 72 controls using whole
      brain tissue volumes extracted from native space and voxel-based morphometry
      (VBM) in normalised space. We applied a qualitative and quantitative review of
      VBM preprocessing and modified the optimised method to establish optimum co
      registration of the brains in normalised space. We report tissue density
      differences at cluster level with adjustment for underlying smoothness.
      Individuals with intellectual disability had smaller total white matter and total
      brain tissue volumes than controls, as well as reduced grey matter density in the
      right cerebellar hemisphere and left temporo-parietal cortex, and reduced white
      matter density in the posterior corpus callosum. Intellectually disabled subjects
      were additionally subgrouped according to their degree of reported autistic
      features. Reduced grey matter density was detected in the thalamus of subjects
      with autistic features scoring within the pervasive developmental disorder range
      as compared to subjects below the threshold for ASD, and increased white matter
      density was detected in the left superior temporal gyrus of subjects scoring
      above the threshold for autism as compared to subjects below the threshold for
      ASD.

PMID- 16996750
TI  - A PET imaging study of 5-HT(1A) receptors in cat brain after acute and chronic
      fluoxetine treatment.
AB  - Immuno-electron microscopic and beta-microprobe studies have demonstrated that
      the internalization of serotonin 5-HT(1A) autoreceptors, after acute treatment
      with the selective 5-HT(1A) receptor agonist 8-OH-DPAT or with the specific
      serotonin reuptake inhibitor (SSRI) fluoxetine, is associated with a marked
      decrease in the in vivo binding of [(18)F]MPPF in the nucleus raphe dorsalis
      (NRD) of rat. To determine whether this event might be amenable to brain imaging,
      the present [(18)F]MPPF positron emission tomographic (PET) study was carried out
      in anesthetized cats given or not a single dose (5 mg/kg, i.v.) or chronically
      treated with fluoxetine (5 mg/kg, s.c. for 21 days). Compared to control,
      [(18)F]MPPF binding potential was considerably (and visibly) decreased in the cat
      NRD after acute fluoxetine treatment, while it remained unchanged in other brain
      regions. Unexpectedly, after chronic fluoxetine treatment, [(18)F]MPPF binding
      potential was not affected in any brain region. In parallel immuno-electron
      microscopic experiments carried out in rat, the density of 5-HT(1A) autoreceptors
      on the plasma membrane of NRD dendrites was comparable to control after chronic
      fluoxetine treatment. If the decrease in [(18)F]MPPF binding at the onset of SSRI
      treatment was detectable by PET imaging, it could potentially serve as a
      biological index of efficacy.

PMID- 16996751
TI  - The influence of sulcal variability on morphometry of the human anterior
      cingulate and paracingulate cortex.
AB  - Human anterior cingulate (ACC) and paracingulate (PaC) cortices play an important
      role in cognitive and affective regulation and have been implicated in numerous
      psychiatric and neurological conditions. The region they comprise displays marked
      inter-individual variability in sulcal and gyral architecture, and although
      recent evidence suggests that this variability has functional significance, it is
      often ignored in automated and region-of-interest (ROI) morphometric
      investigations. This has lead to confounded interpretation of results and
      inconsistent findings across a number of studies and in a variety of clinical
      populations. In this paper, we present a reliable method for parcellating the
      dorsal, ventral, and subcallosal ACC and PaC that accounts for individual
      variation in the local cortical folding pattern. We also investigated the effect
      of one well characterized morphological variation, the incidence of the
      paracingulate sulcus (PCS), on regional volumes in 24 (12 male, 12 female)
      healthy participants. The presence of a PCS was shown to affect both ACC and PaC
      volumes, such that it was associated with an 88% increase in paracingulate cortex
      and a concomitant 39% decrease in cingulate cortex. These findings illustrate the
      potential confounds inherent in morphometric approaches that ignore or attempt to
      minimize inter-individual variations in sulcal and gyral anatomy and underscore
      the need to consider this variability when attempting to understand disease
      processes or characterize brain structure-function relationships.

PMID- 16996752
TI  - Biological assay using T cell response for Cry-consensus peptide designed for the
      peptide-based immunotherapy of Japanese cedar pollinosis.
AB  - INTRODUCTION: Cry-consensus peptide is a linearly linked peptide of T-cell
      epitopes for the management of Japanese cedar (JC) pollinosis and is expected to
      become a new drug for immunotherapy. However, the mechanism of T-cell epitopes in
      allergic diseases is not well understood, and thus, a simple in vitro procedure
      for evaluation of its biological activity is desired. METHODS: Peripheral blood
      mononuclear cells (PBMC) were isolated from 27 JC pollinosis patients and 10
      healthy subjects, and cultured in vitro for 4 days in the presence of Cry
      consensus peptide and (3)H-thymidine. The relationship between growth stimulation
      (stimulation index; SI) and antigen-specific IgE levels in serum was also
      investigated in JC pollinosis patients. Moreover, to confirm the importance of
      the primary sequence in Cry-consensus peptide, heat-treated Cry-consensus peptide
      and a mixture of the amino acids of which Cry-consensus peptide is composed, and
      their (3)H-thymidine uptake was compared with Cry-consensus peptide. Finally,
      whether Cry-consensus peptide stimulates PBMCs from healthy subjects was
      investigated. RESULTS: The mean SI of JC patients showed a good correlation with
      Cry-consensus peptide concentration in the culture medium; however, the SI was
      independent of the anti-Cry j 1 IgE level. Heat-denatured Cry-consensus peptide
      retained a PBMC proliferation stimulatory effect comparable to the original Cry
      consensus peptide, while the mixture of amino acids constituting Cry-consensus
      peptide did not stimulate PBMC proliferation. PBMCs from healthy subjects did not
      respond to Cry-consensus peptide at all. DISCUSSION: These data indicate that the
      PBMC response of patients suffering from JC pollinosis to Cry-consensus peptide
      is specific for the sequence of T cell epitopes thereof and may be useful for the
      evaluation of the efficacy of Cry-consensus peptide in vivo.

PMID- 16996753
TI  - Band 3 (AE1, SLC4A1)-mediated transport of stilbenedisulfonates. II: Evidence for
      transmembrane allosteric interactions between the "primary" stilbenedisulfonate
      binding site and the stilbenedisulfonate efflux site.
AB  - Results from the first paper in this series indicated that the "primary"
      stilbenedisulfonate (PSD) site was not located on the DBDS (4, 4'-dibenzamido-2,
      2'-stilbenedisulfonate) transport pathway into magnesium resealed ghosts (MRSG).
      Rather, transport correlated with DBDS binding to the "second" class of proton
      activated binding sites located on the membrane domain of band 3 [Biochem. J. 388
      (2005) 343]. Here we report the discovery that reversible binding of
      extracellular H2DIDS (4, 4'-diisothiocyanatodihydro-2, 2'-stilbenedisulfonate) to
      the PSD site causes a greater than 5-fold acceleration in the rate of DBDS efflux
      from pre-loaded MRSG at physiological pH. Pre-labeling all of the PSD sites with
      H2DIDS inhibited the acceleration effect completely, thus confirming mediation by
      band 3. Acceleration of DBDS efflux could be mimicked by establishing an
      externally directed proton gradient (acidic inside, pH 7.4 outside). Under these
      conditions, addition of extracellular H2DIDS neither accelerated DBDS efflux
      further nor was proton-induced acceleration inhibited. The results of this paper
      support the view that the PSD binding site on band 3 is an allosteric regulatory
      site which is not located on the SD transport pathway. We propose a model where
      H2DIDS binding to the PSD site modulates activity at the "second" class of sites
      by raising the pK for transport of DBDS into the physiological pH range.

PMID- 16996754
TI  - Helicobacter pylori infection and HFE hemochromatosis.
AB  - Helicobacter pylori infections are associated with iron deficiency, even in the
      absence of bleeding. To determine whether H. pylori infection plays a role in
      modifying the phenotype of patients homozygous for the c.845 G > A (C282Y)
      mutation of the HFE gene we studied 79 homozygous women and 76 homozygous men,
      comparing the pretreatment hemoglobin, MCV, serum ferritin, transferrin
      saturation of those who were seropositive and seronegative for H. pylori. No
      difference between seropositive and seronegative homozytoes was found. There was
      also no difference between seropositive and seronegative control subjects. We
      also compared the total iron of 56 of the male and 32 of the female homozygotes
      as determined by serial phlebotomy. No significant difference was found.

PMID- 16996755
TI  - Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway
      in anterior pituitary cells.
AB  - We previously showed that long-term exposure of anterior pituitary cells to
      nitric oxide (NO) induces apoptosis. The intracellular signals underlying this
      effect remained unclear. In this study, we searched for possible mechanisms
      involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated
      by NO with no apparent disruption of mitochondrial membrane potential. NO caused
      a rapid increase of reactive oxygen species (ROS), and this increase seems to be
      dependent of mitochondrial electron transport chain. The antioxidant N-acetyl
      cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and
      reduced the NO apoptotic effect. Catalase was inactivated by NO, while
      glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not
      modified at first, but increased at later times of NO exposure. The increase of
      GSH level is important for the scavenging of the NO-induced ROS overproduction.
      Our results indicate that ROS have an essential role as a trigger of the NO
      apoptotic cascade in anterior pituitary cells. The permanent inhibition of
      catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH
      level augment in response to the oxidative damage, though this increase seems not
      to be enough to rescue the cells from the NO effect.

PMID- 16996756
TI  - Fracture rate in Thoroughbred racehorses is affected by dam age and parity.
AB  - This study's aim was to determine the effects of dam age and parity on the rate
      of fracture in offspring in Thoroughbred racehorses in training for flat racing.
      It was hypothesised that first foals and those from older mares would have a
      higher fracture rate than subsequent foals and those from younger mares. A two
      year observational cohort study collected data from eight trainers on 335 horses
      that were monitored since the start of their training as yearlings. Multivariable
      Poisson regression analyses showed that first foals had a significantly lower
      fracture rate than subsequent ones (RR=0.33; 95% CI=0.12, 0.89; P=0.02) and rate
      of fracture decreased with increasing dam age (RR=0.91 per year increase in dam
      age; 95% CI=0.83, 0.99; P=0.03). This study shows for the first time that the
      rate of equine injury may be influenced by factors that affect skeletal
      development. Further research on intra-uterine and peri-natal determinants of
      injury risk in later life in horses is needed.

PMID- 16996757
TI  - Transient acute obstructive hydrocephalus of unknown origin in a 13-month-old
      infant.
AB  - We report on a case of a 13-month-old female infant who was admitted to our
      department with the chief complaints of drowsiness and vomiting. A history of an
      unspecified viral infection was reported. Clinical examination was negative for
      focal neurological signs or signs of central nervous system infection. Initial CT
      scan revealed obstructive hydrocephalus, and shunting was scheduled.
      Dexamethasone treatment was started. Eight hours after admission the child almost
      restored his baseline mental status and the operation was postponed. The
      dexamethasone treatment was discontinued 3 days later. Follow up CT and MRI scans
      were normal. We discuss the case and the possible causes of transient
      hydrocephalus in children.

PMID- 16996758
TI  - Rotary resonance echo double resonance for measuring heteronuclear dipolar
      coupling under MAS.
AB  - A rotary resonance echo double resonance (R-REDOR) experiment is described for
      measuring heteronuclear dipolar coupling under magic-angle spinning. Rotary
      resonance reintroduces both dipolar coupling and chemical shift anisotropy with
      an rf field matching the spinning frequency. The resonance effect from chemical
      shift anisotropy can be refocused with a rotary resonance echo. The R-REDOR
      experiment thus measures the dephasing of the rotary resonance echo from the
      heteronuclear dipolar coupling to determine the dipolar coupling constant. The
      rotary resonance experiment is suitable for measuring dipolar coupling with
      quadrupolar nuclei because it applies the recoupling rf only to the observed spin
      1/2. The rotary resonance scheme has the advantages of a long T2' and susceptible
      to spinning frequency fluctuation.

PMID- 16996759
TI  - A constant gradient unilateral magnet for near-surface MRI profiling.
AB  - The design and construction of a unilateral NMR (UMR) magnet assembly for near
      surface 1D profiling is presented. The arrangement consists of a single permanent
      magnet topped with a shaped iron pole cap. The analytically determined profile of
      the pole cap shapes the field over the magnet, giving a constant gradient of 31
      G/cm over a 8mm depth at a 1H frequency of 4.26 MHz in a spot approximately 5 mm
      wide. The moderate gradient allows 1D profiling of planar samples with a
      frequency encoded spin-echo experiment. The curvature of the magnetic field
      limits the available resolution to 100's of microm. The device is suitable for
      profiling planar samples in which a coarse resolution but large spatial extent is
      desired.

PMID- 16996760
TI  - A general numerical analysis of time-domain NQR experiments.
AB  - We introduce a general numerical approach for solving the Liouville equation of
      an isolated quadrupolar nuclide that can be used to analyze the unitary dynamics
      of time-domain NQR experiments. A numerical treatment is necessitated by the
      dimensionality of the Liouville space, which precludes analytical, closed form
      solutions for I > 3/2. Accurate simulations of experimental nutation curves,
      forbidden transition intensities, powder and single crystal spectra, and off
      resonance irradiation dynamics can be computed with this method. We also examine
      the validity of perturbative approximations where the signal intensity of a
      transition is proportional to the transition moment between the eigenstates of
      the system, thus providing a simple basis for determining selection rules. Our
      method allows us to calculate spectra for all values of the asymmetry parameter,
      eta, and sample orientations relative to the coil axis. We conclude by
      demonstrating the methodology for calculating the response of the quadrupole
      system to amplitude- and frequency-modulated pulses.

PMID- 16996761
TI  - Pyrolysis mechanism of carbon matrix precursor cyclohexane--the formation of
      condensed-ring aromatics and the growing process of molecules.
AB  - Based on the experiments, the UAM1 method was adopted to investigate benzene
      condensation of an important intermediate and the molecule growing mechanism
      during the cyclohexane pyrolysis process. The conclusions were drawn as follows:
      (1) from the viewpoint of thermodynamics, the condensation of benzene and C4H5*
      is a spontaneous reaction and the rising temperature will increase the
      spontaneous tendency of the reaction. (2) From the viewpoint of kinetic, the
      condensation of benzene and C4H5* is a two-step reaction. The rate-determining
      step is step 2 of hydrogen removal from intermediate C10H10 (I1) with the
      activation energy of 350.61 kJ/mol below 1473 K while the rate-determining step
      is step 1 that free radical C4H5* attacks benzene to form intermediate C10H10
      (I1) with the activation energy DeltaE(0)(not equal to theta)=31.74 kJ/mol above
      1473 K. (3) The space structure, electronic structure and thermodynamics
      parameters of molecular reaction of dense-ring aromatizing compounds can be used
      to replace the resonance energy and free valence to judge the activation of
      thermodynamic reaction of compounds. And (4) the analysis of the space structure,
      electronic structure and thermodynamic parameters show that the growing process
      of molecules with benzene used as initial reactants becomes more easier as the
      multi-ring aromatizing molecular system increases.

PMID- 16996762
TI  - Increased human placental growth hormone at midtrimester pregnancies may be an
      index of intrauterine growth retardation related to preeclampsia.
AB  - OBJECTIVE: To evaluate the relationship between maternal serum and amniotic fluid
      levels of human Placental Growth Hormone (hPGH) with the fetal intrauterine
      growth retardation (IUGR) related to preeclampsia. DESIGN: We analyzed samples in
      pairs of serum and amniotic fluid retrospectively from 25 women, who manifested
      preeclampsia and IUGR in the late second or the third trimester of gestation. The
      samples were obtained at 16-22 weeks' gestation during amniocentesis for fetal
      karyotyping. At this time, there was no clinical or sonographic evidence of
      preeclampsia or IUGR, respectively. Sixty-two serum samples were used as controls
      which were obtained at 16-22 weeks' gestation from women with singleton,
      uncomplicated pregnancies, with normal outcome, and appropriate for gestational
      age neonatal birth weight. Forty-seven amniotic fluid samples were also used as
      controls which were obtained at 16-22 weeks' gestation from the women that were
      included in the control group who underwent an amniocentesis. hPGH levels were
      measured by a solid phase immunoradiometric assay. RESULTS: The mean hPGH values
      in the serum and the amniotic fluid of the IUGR related to preeclampsia affected
      pregnancies were significantly higher (P<0.05) than those of the normal
      pregnancies at 16-22 weeks' gestation: mean+/-SD in the serum was 13.16+/-10.52
      ng/ml vs. 4.39+/-2.23 ng/ml; mean+/-SD in the amniotic fluid 2.49+/-1.6 ng/ml vs.
      0.82+/-0.67 ng/ml. CONCLUSION: hPGH levels in maternal serum and amniotic fluid
      were found to be higher at 16-22 weeks' gestation in pregnancies that will be
      complicated subsequently by IUGR related to preeclampsia. Our findings suggest
      that the evaluation of the changes of hPGH levels at midtrimester should be
      further investigated for the possibility to provide a potential predictive index
      of IUGR and preeclampsia.

PMID- 16996763
TI  - Metabolic engineering of the heterologous production of clorobiocin derivatives
      and elloramycin in Streptomyces coelicolor M512.
AB  - The aminocoumarin antibiotic clorobiocin is a potent inhibitor of bacterial
      gyrase. Two new analogs of clorobiocin could be obtained by deletion of a
      methyltransferase gene, involved in deoxysugar biosynthesis, from the
      biosynthetic gene cluster of clorobiocin, followed by expression of the modified
      cluster in the heterologous host Streptomyces coelicolor M512. However, only low
      amounts of the desired glycosides were formed, and aminocoumarins accumulated
      predominantly in form of aglyca. In the present study, we clarified the limiting
      steps for aminocoumarin glycoside formation, and devised strategies to improve
      glycosylation efficiency. Heterologous expression of a partial elloramycin
      biosynthetic gene cluster indicated that the rate of dTDP-L-rhamnose synthesis,
      rather than the rate of glycosyl transfer, was limiting for glycoside formation
      in this strain. Introduction of plasmid pRHAM which contains four genes from the
      oleandomycin biosynthetic gene cluster, directing the synthesis of dTDP-rhamnose,
      led to a 26-fold increase of the production of glycosylated aminocoumarins.
      Expression of the 4-ketoreductase gene oleU alone resulted in an 8-fold increase.
      Structural investigation of the resulting deoxysugars confirmed that both the
      endogeneous and the heterologous pathway involve a 3,5-epimerization of the
      deoxysugar, a hypothesis which had recently been questioned.

PMID- 16996764
TI  - Impact of RNA interference on gene networks.
AB  - Small endogenous RNAs such as microRNAs (miRNAs) and small interfering RNAs
      (siRNAs) have been found to post-transcriptionally control cellular gene networks
      by targeting complementary mRNAs for translation impairment (miRNA) or
      destruction (siRNA). We have developed a computational model, coordinated to
      molecular and biochemical parameters of RNA interference pathways, to provide
      (semi-) quantitative insight into the molecular events managing siRNA-mediated
      gene expression silencing in native and synthetic gene networks. Based on mass
      conservation principles and kinetic rate laws, we converted biochemical RNA
      interference pathways into a set of ordinary differential equations that describe
      the dynamics of siRNA-mediated translation-regulation in mammalian cells.
      Capitalizing on mechanistic details of synthetic transactivator operation, we
      wired this model into a transcription control circuitry in which the siRNA and
      its target mRNA are independently regulated at the transcriptional level. In this
      context, we studied the impact of siRNA transcription timing on the onset of
      target gene transcription and production kinetics of target mRNA-encoded
      proteins. We also simulated the rate of siRNA-induced mRNA depletion and
      demonstrated that the relative concentrations of interacting siRNAs/mRNAs and the
      number of siRNA-specific target sites on a transcript modulate (i) the rate of
      target mRNA disappearance, (ii) the steady-state mRNA levels and (iii) induction
      dynamics of mRNA-encoded protein production. As our model predictions are
      consistent with available biochemical parameters, extrapolations may improve our
      understanding of how complex regulatory gene networks are impacted by small
      endogenous RNAs.

PMID- 16996765
TI  - Phenotypic and genotypic heterogeneity in Gaucher disease type 1: a comparison
      between Brazil and the rest of the world.
AB  - Type 1 Gaucher disease, the most common lysosomal storage disorder, results from
      deficiency of glucocerebrosidase causing pathologic accumulation of
      glucocerebroside. The disease is characterized by marked variation in age of
      onset and degree of anemia, thrombocytopenia, hepatosplenomegaly, and skeletal
      disease. Most published data on Gaucher disease come from populations with large
      proportions of Ashkenazi-Jewish patients, who tend to have less severe disease.
      We compared selected demographic, clinical, and genetic parameters for Brazilian
      (N = 221) and rest-of-world (N = 1477) type 1 Gaucher disease patients entered
      into the ICGG Gaucher Registry since 1991. We also compared Brazilian patients to
      non-Ashkenazi rest-of-world patients (N = 692) to determine if differences were
      the result of fewer Brazilian Ashkenazi-Jewish patients (0.5% vs 45.0%). The
      Brazilian cohort differed significantly (p < 0.05) from the rest-of-world and
      rest-of-world non-Ashkenazi cohort, respectively, in the following measures:
      higher proportion of females (59.7% vs 50.4% and 49.7%), lower mean age at
      diagnosis (17.1 vs 24.1 and 18.8), and higher proportions of patients with anemia
      (55.5% vs 29.9% and 35.7%), bone pain (57.7% vs 33.7% and 35%), bone crises
      (16.1% vs 6.5% and 7.4%), and lytic lesions (17.0% vs 7.6% and 7.4%). The most
      common genotype in Brazil was N370S/L444P (c1448T-->C/c1226A-->C) (46.8% versus
      16.3% and 25.7%). These data highlight the genetic and phenotypic heterogeneity
      among geographic populations of type 1 Gaucher patients and suggest that as a
      group, Brazilian patients may have a more aggressive form of the disease than
      rest-of-world patients. The findings also emphasize the need for caution in
      making generalizations about Gaucher disease across demographic groups.

PMID- 16996766
TI  - Stop codon mutations in the flavin-containing monooxygenase 3 (FMO3) gene
      responsible for trimethylaminuria in a Japanese population.
AB  - The reduced capacity of flavin-containing monooxygenase 3 (FMO3) to N-oxidize
      trimethylamine (TMA) is believed to cause a metabolic disorder. The aim of this
      study was to investigate the inter-individual variations of FMO3. Genomic DNA of
      case subjects that showed only 10-20% of FMO3 metabolic capacity among self
      reported trimethylaminuria Japanese volunteers was sequenced. Functional analysis
      of recombinant FMO3 proteins was also performed. One homozygote for a novel
      single nucleotide substitution causing a stop codon at Arg500 was observed. The
      biological parents of this Proband A were heterozygous and showed >90% TMA N
      oxygenation metabolic capacity. Another Proband B had the Arg500Stop and
      Cys197Stop codons. The TMA N-oxygenation metabolic capacities of the father and
      brother of this Proband B were apparently observed by possessing Arg205Cys mutant
      that coded for decreased TMA N-oxygenase. Recombinant Arg500Stop FMO3 cDNA
      expressed in Escherichia coli membranes and a series of highly purified
      truncation mutants at different positions of the C-terminus of FMO3 showed no
      detectable functional activity toward typical FMO3 substrates. The results
      suggest that individuals homozygous for either of the nonsense mutations,
      Arg500Stop and/or Cys197Stop alleles, in the FMO3 gene can possess abnormal TMA N
      oxygenation.

PMID- 16996767
TI  - [Therapeutic communication of blood: elements for a phenomenologic social
      psychology of the living].
AB  - Blood is the most available and admissible of substitutive human products.
      However, neither an attitude favourable to its therapeutic transfusion nor a
      positive representation of blood is sufficient to predict an effective gift or an
      absence of fear to its reception. In this article, we synthesize various research
      of social psychology aiming at understanding what are these different bloods that
      the subjects accept or refuse to communicate. In order to give a new
      interpretation of the problems of the social communication of substitutive human
      product, we will evoke practice, attitudes and representations of blood starting
      from a model including seven factors of representation of biological materials -
      this model reflecting dimensions on which is based the intersubjective social
      network in which is carried out the therapeutic communication of blood.

PMID- 16996768
TI  - Paradigms, emperor's clothes syndrome, and hidden curriculum: how do they affect
      joint, bone, and spine diseases?

PMID- 16996769
TI  - Unusual presentation of isolated sacral tuberculosis.
AB  - Tuberculosis is as old as mankind. Vertebral tuberculosis is fairly common form
      of bone and joint tuberculosis. However, isolated sacral tuberculosis is rare. It
      may present as an atypical sacral lesion having epidural granuloma without
      destruction of sacrum on MRI and plain X-rays. This atypical presentation may
      lead to delay in diagnosis and treatment. This case report intends to emphasize
      that spinal tuberculosis should be the first and foremost differential diagnosis
      in the presence of atypical clinical and radiological features of a sacral lesion
      particularly in developing countries. Early diagnosis and treatment can prevent
      or minimize the neurological morbidity in such cases.

PMID- 16996770
TI  - [Staying fit after fifty].
AB  - It is common knowledge that when women reach the menopause, they put on weight
      and change body shape. The menopause is particularly feared as a sign of aging.
      The deficiency in estrogen at the menopause is responsible for the change from a
      gynoid fat pattern to an android one (i.e. fat accumulates on the upper portion
      of the abdomen instead of on the hips). In addition, women are no longer
      protected against CardioVascular Diseases (CVD), and will rapidly share the same
      risks as men. The menopause is marked by an increase in the prevalence of various
      CVD risk factors: elevated blood pressure, hypertriglyceridemia, Diabetes, etc.
      This phenomenon may be explained by an increase in the occurrence of the
      polymetabolic (PM) syndrome at this time of life. In the IDF ((International
      Diabetics Federation) 2005 definition, waist circumference becomes the main
      criterion of PM syndrome. Keeping a slim waist can no longer be considered a
      woman's vain obsession but a justified health concern, since the waist to height
      ratio is a better predictor of CVD than BMI (Body Mass Index). A diet and
      healthcare program is now available which, if followed from the age of 35, can
      help women live 'in good shape' and for longer.

PMID- 16996771
TI  - [Long-term effects of environmental endocrine disruptors on male fertility].
AB  - Several epidemiologic studies have demonstrated during the last 50 years an
      increased incidence in testis cancer, male genital tract malformations
      (cryptorchidism and hypospadias) and a decrease in sperm quality in men. These
      three pathologies seem to be linked and to belong to the testicular dysgenesis
      syndrome (TDS). It was suggested that TDS is a consequence of intra-uterine
      exposure to environmental compounds that disrupt the metabolism of native
      hormones. Such substances are so called endocrine disruptors (EDs). EDs are
      present in our daily environment such as food and water (through the use of
      pesticides), cosmetics, house-care products etc. Experimental models have been
      carried out to (i) establish a link between EDs exposure and SDT and (ii)
      identify the mechanisms that are involved in. After a brief definition of EDs and
      having underlined the importance of the window of exposure to EDs, several
      mechanisms will be described such as (i) intergenerational transmission
      (epigenetic), (ii) programmed cell death of testicular cells, (iii) modification
      of the androgenic signal and (iv) role of the germ cells-nourishing cells. To
      conclude, we will try to propose some biomarkers that would be useful to identify
      the potential link between fetal exposure to anti-androgenic EDs and male
      testicular pathology.

PMID- 16996772
TI  - [Renal angiomyolipoma rupture during pregnancy].
AB  - A 40 year-old 2nd gesta pregnant woman (34.5 weeks of amenorhea) was admitted to
      hospital for abdominal pain and arterial hypotension which were rapidly related
      to a retroperitoneal haematoma due to left kidney bleeding. Emergency cesarean
      delivery under general anaesthesia was undertaken because of foetal distress.
      Exploration of the retroperitonal space after foetal extraction confirmed the
      presence of a large haematoma and abnormal left renal morphology. The
      retroperitoneal space was drained without any further intervention. Subsequently,
      abdominal and thoracic computerised tomographic examination showed bilateral
      dysplasia of the kidneys and pulmonary cysts consistent with the diagnosis of
      renal angiomyolipoma and pulmonary lymphangioleiomyomatosis. The case report is
      of interest because of the circumstances of discovery of the disease and because
      nephrectomy was not necessary to control the bleeding of the left kidney. Six
      months after the incident the patient and the child are in good condition.

PMID- 16996773
TI  - Robust measures of three-dimensional vascular tortuosity based on the minimum
      curvature of approximating polynomial spline fits to the vessel mid-line.
AB  - The clinical recognition of abnormal vascular tortuosity is important in the
      diagnosis of many diseases. This paper presents a novel approach to the
      quantification of vascular tortuosity, using robust metrics based on unit speed
      parameterizations of three-dimensional (3D) curvature. The use of approximating
      polynomial spline-fitting obviates the need for arbitrary filtering of mid-line
      data which is necessary with other tortuosity indices. The metrics were tested
      using both two-dimensional and three-dimensional synthesized images that mimicked
      clinically significant pathologies: two of the three metrics were scale
      invariant, additive, and produced tortuosity values tailored to be independent of
      the resolution of the imaging system. Our methodology is designed to explicitly
      handle the challenge of noisy data, and is largely tolerant of the inaccuracies
      in the mid-line extraction. While all the proposed metrics are sensitive to
      gently curved vessels, the rms curvature of the smoothest path was more effective
      in recognizing abnormalities involving high-frequency coiling such as occurs in
      malignant tumors. We have also indicated how values from two projection images,
      such as acquired in biplane angiography, can be combined to give an accurate
      approximation of the 3D value of this metric. Our proposed methodology is well
      suited to automated detection and measurement, which are a prerequisite for
      clinical implementation.

PMID- 16996774
TI  - Noise reduction in Doppler ultrasound signals using an adaptive decomposition
      algorithm.
AB  - A novel de-noising method for improving the signal-to-noise ratio (SNR) of
      Doppler ultrasound blood flow signals, called the matching pursuit method, has
      been proposed. Using this method, the Doppler ultrasound signal was first
      decomposed into a linear expansion of waveforms, called time-frequency atoms,
      which were selected from a redundant dictionary named Gabor functions.
      Subsequently, a decay parameter-based algorithm was employed to determine the
      decomposition times. Finally, the de-noised Doppler signal was reconstructed
      using the selected components. The SNR improvements, the amount of the lost
      component in the original signal and the maximum frequency estimation precision
      with simulated Doppler blood flow signals, have been used to evaluate a
      performance comparison, based on the wavelet, the wavelet packets and the
      matching pursuit de-noising algorithms. From the simulation and clinical
      experiment results, it was concluded that the performance of the matching pursuit
      approach was better than those of the DWT and the WPs methods for the Doppler
      ultrasound signal de-noising.

PMID- 16996775
TI  - Snapshots and snippets: general practitioners' reflections on professional space.
AB  - The paper presents the results of a mixed methods study of British general
      practitioners' (GPs) reflections on professional space in terms of practice and
      self-identity. Inter-textual content analysis of 12 biographic and photographic
      datasets revealed four themes: workspace, re-appropriated space, life space and
      sacred space. GPs are ambivalent about their working environments, spending time
      and energy creating 'best fit' spaces, until lack of function becomes an
      habituated part of daily routine. Whilst some appear helpless in the face of
      change, others are making their presence felt through embodied, personalized or
      authorial spaces.

PMID- 16996776
TI  - The inhibitory pathways of pancreatic ductal bicarbonate secretion.
AB  - Pancreatic duct cells secrete the HCO(3)(-) ions found in pancreatic juice. While
      the regulatory pathways that stimulate pancreatic ductal HCO(3)(-) secretion are
      well described, little is known about inhibitory pathways, apart from the fact
      that they exist. Nevertheless, such inhibitory pathways may be physiologically
      important in terms of limiting the hydrostatic pressure within the lumen of the
      duct, and in terms switching off pancreatic secretion after a meal. Methionine
      encephalin, insulin, somatostatin, peptide YY, substance P, basolaterally applied
      adenosine triphosphate, arginine vasopressin, 5-hydroxytryptamine and epidermal
      growth factor have all been shown to inhibit fluid and/or HCO(3)(-) secretion
      from pancreatic ducts. Importantly, most of these inhibitors have been shown to
      reduce secretion in isolated pancreatic ducts, so they must act directly on the
      ductal epithelium. This brief review provides an overview of our current
      knowledge of the inhibitors, and inhibitory pathways of pancreatic ductal
      secretion. SIGNALLING NETWORK FACTS: Methionine encephalin, insulin,
      somatostatin, peptide YY, substance P, basolaterally applied adenosine
      triphosphate, arginine vasopressin, 5-hydroxytryptamine and epidermal growth
      factor have all been shown to inhibit fluid and/or HCO(3)(-) secretion from
      pancreatic ducts. The inhibition of pancreatic secretion can be mediated by
      indirect (decreased cholinergic or increased adrenergic stimulation, decreased
      release of stimulatory hormones) and direct (inhibitory hormone or
      neurotransmitter acting on the duct cells) mechanisms.

PMID- 16996777
TI  - T4b oral cavity cancer below the mandibular notch is resectable with a favorable
      outcome.
AB  - According to the AJCC 2002 staging system, squamous cell carcinoma of the oral
      cavity (OSCC) with T4b is unresectable. Herein, we report on our surgical outcome
      for T4b OSCC. All patients were enrolled before 2002. From January 1996 to
      December 2000, 45 consecutive untreated T4b OSCC patients were included.
      According to the trans-axial plane of the mandibular notch on CT/MRI, seven were
      supra-notch T4b and 38 were infra-notch T4b tumors. Significantly higher 5-year
      loco-regional control and survivals were observed in patients with infra-notch
      T4b than with supra-notch T4b. In the infra-notch group, pN0-1 patients had a
      significantly higher 5-year loco-regional control and survivals than pN2
      patients. Nerve invasion was the sole significant adverse factor for loco
      regional control and survivals in the infra-notch T4b group with pN0-1. Our
      retrospective study demonstrated that OSCC patients of infra-notch T4b with pN0-1
      and no nerve invasion might have a favorable surgical outcome.

PMID- 16996778
TI  - Evidence of lymphangiogenesis in Warthin's tumor of the parotid gland.
AB  - The details of the pathogenesis of cystadenolymphoma (Warthin's tumor) of the
      parotid gland are still unclear. Neovascularization is considered to be a pivotal
      factor for solid tumor progression and biological behavior of the tumor. Using
      double-labeling immunohistochemistry for LYVE-1 and CD34 (specific markers for
      lymphatic and vascular endothelial cells, respectively) this study analyzes
      lymphatic vessel density (LVD) and blood vessel density (BVD) in 10 Warthin's
      tumors and 10 pleomorphic adenomas of the parotid gland as well as in 5 normal
      parotid glands and 5 normal parotid lymph nodes. There was no significant
      difference in the intratumoral LVD and BVD among pleomorphic adenoma and normal
      parotid gland tissue. In contrast, the intratumoral LVD and BVD were
      significantly higher in Warthin's tumor than pleomorphic adenoma, normal parotid
      gland and parotid lymph node (P<0.0001 versus P<0.004). The increase in lymphatic
      vessels in Warthin's tumor suggests that epithelial tumor cells might promote
      lymphangiogenesis in this kind of lesions.

PMID- 16996779
TI  - Oral cancer knowledge and awareness: primary and secondary effects of an
      information leaflet.
AB  - Information leaflets can be stored and read several times at the patient's own
      convenience and speed and, therefore, might contribute to increasing the long
      term oral cancer knowledge and awareness. This hypothesis was investigated in a
      sample of adults living in a small central Italian town. The two groups of
      patients selected (Intervention, 100 subjects; Control, 84 subjects) were all
      aged 40 years and had never received oral cancer counselling or examination
      previously. Subjects completed a questionnaire (PRE) containing items regarding
      oral cancer epidemiology and prevention. Thereafter, the Intervention patients
      received the oral cancer information leaflet. One year later, patients from both
      groups were re-contacted and most (97 Intervention, 79 Control subjects, overall
      participation rate, 95.7%) completed the same questionnaire (POST). The POST
      questionnaire score, the score increment and the proportion of patients who
      sought an oral cancer examination during the year follow-up were used as markers
      of long-term knowledge, knowledge improvement and awareness, respectively. The
      between group differences in mean PRE score, POST score, score increment and
      proportion of subjects who had an examination were assessed by conventional
      statistical tests. The effect of leaflet corrected for confounders also was
      assessed using multiple regression analyses. No difference in PRE score and
      awareness was found. However, the mean POST score and the score increment were
      significantly higher in the Intervention group. The leaflet significantly
      increased knowledge but not awareness, with statistically significant effects
      from high educational level and younger age. It is concluded that the information
      leaflet had a significant effect in raising the long-term oral cancer knowledge
      in the general public. It also had a secondary effect on disease awareness in the
      locale.

PMID- 16996780
TI  - Multipotency of CD11bhighGr-1+ immature myeloid cells accumulating in oral
      squamous cell carcinoma-bearing mice.
AB  - We demonstrated the accumulation of CD11b(high)Gr-1(+) cells in a murine model of
      squamous cell carcinoma (SCC). Inoculation of NR-S1K cells derived from oral SCC
      induced a rapid and clear accumulation of CD11b(high)Gr-1(+) cells in secondary
      lymphoid organs as well as in peripheral blood. Phenotypic and morphological
      analyses revealed that these CD11b(high)Gr-1(+) cells were not lymphoid lineage
      cells, mature dendritic cells, macrophages, or granulocytes. Although the freshly
      isolated CD11b(high) cells lacked antigen-presenting capacity, they acquired a
      potent antigen-presenting capacity that included the induction of MHC class II
      after culture with GM-CSF and IL-4 in vitro. These results suggest that
      CD11b(high) cells that accumulate in tumor-bearing hosts are immature myeloid
      cells, but have considerable potential to differentiate into potent antigen
      presenting cells under appropriate culture conditions. The use of in vitro
      differentiated CD11b(high) cells may be a potential strategy for obtaining
      patient-matched dendritic cells for tumor immunotherapy.

PMID- 16996782
TI  - Galectin-3 immunoprofile in adenoid cystic carcinoma and polymorphous low-grade
      adenocarcinoma of salivary glands.
AB  - Adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA)
      are malignant neoplasms of salivary glands, which are similar in histologic
      patterns but very different in clinical behavior, treatment and prognosis.
      Galectin-3 is a multifunctional protein of a growing family of beta-galactoside
      binding animal lectins, which is implicated in a variety of biological events
      such as tumor cell adhesion, proliferation, differentiation and angiogenesis.
      This protein was found to be implicated in cellular transformation and a
      correlation between its expression and cancer progression and metastasis has been
      described. The aim of this study was to determine the galectin-3 immunoprofile in
      14 cases of ACC (2 cases of tubular subtype, 4 cases of solid subtype and 8 cases
      of cribriform subtype) and in 12 cases of PLGA with different histologic
      patterns, including lobular, tubular and cribriform aspects. Moreover, slides of
      normal salivary glands were included. In normal salivary glands there was strong
      nuclear and cytoplasmic staining for galectin-3 in ductal luminal cells. ACC
      showed specific staining in luminal cells mainly in the nuclei. In the tubular
      subtype of ACC, galectin-3 strongly stained luminal cells of the ductiform
      structures. The cribriform and solid subtypes showed a few positive luminal cells
      of small ducts present in the cribriform structures and in solid nests
      respectively. In the cases of PLGA, independent of the histologic architecture,
      all tumor cells revealed a positive cytoplasmic reaction. Galectin-3 expression
      seems to be related to cell differentiation more than to tumor progression and
      prognosis in the neoplasms studied.

PMID- 16996781
TI  - MGMT expression in oral precancerous and cancerous lesions: correlation with
      progression, nodal metastasis and poor prognosis.
AB  - Alkylation of DNA at the O(6) position of guanine is a critical step in the
      induction of mutations by carcinogenic and chemotherapeutic alkylating agents.
      O(6)-methylguanine-DNA methyltransferase (MGMT) is an enzyme that removes
      mutagenic adducts from the O(6) position of guanine, thereby protecting the
      genome against guanine to adenine transitions. We hypothesized that alteration in
      MGMT expression might occur in early stages of development of oral cancer and be
      associated with disease progression. Immunohistochemical analysis of MGMT
      expression was carried out in 107 oral squamous cell carcinomas (OSCCs), 78 oral
      precancerous lesions (OPLs) (58 hyperplasias and 20 dysplasias) and 30
      histologically normal oral tissues and correlated with clinicopathological
      parameters as well as major risk factors. Decreased MGMT expression was observed
      as early as in hyperplasia (p=0.003; Odd's Ratio (OR)=5.0). Significant loss of
      MGMT expression was observed from hyperplasia to dysplasia (p=0.034; OR=4.0).
      Loss of MGMT expression was associated with late clinical stage of OSCCs
      (p=0.027, OR=2.0) and nodal metastasis (p=0.031, OR=2.5). Decreased MGMT
      expression was associated with smokeless tobacco (ST) consumption in patients
      with OPLs (p=0.017, OR=3.6) and OSCCs (p=0.031, OR=2.8). Significant association
      was also observed between loss of MGMT expression and poor prognosis of OSCC
      patients (p=0.02; OR=5.2). The decreased MGMT expression in OPLs suggested that
      deregulation of MGMT expression is an early event in the development of oral
      cancer. In OSCCs, its correlation with late clinical stage, and nodal metastasis
      suggests association with aggressive tumor behavior and cancer progression,
      underscoring its potential as a candidate predictive marker for nodal metastasis
      and disease prognosis. Correlation of loss of MGMT expression with ST consumption
      underscored its significance in ST-associated oral carcinogenesis.

PMID- 16996783
TI  - Rehabilitation of oral function in head and neck cancer patients after
      radiotherapy with implant-retained dentures: effects of hyperbaric oxygen
      therapy.
AB  - Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy
      often result in an anatomic and physiological oral condition unfavorable for
      prosthodontic rehabilitation. The objective of this prospective study was to
      assess the effect of hyperbaric oxygen therapy on treatment outcome (condition of
      peri-implant tissues, implant survival, oral functioning and quality of life) of
      prosthodontic rehabilitation with implant-retained lower dentures in radiated
      head and neck cancer patients 6 weeks and 1 year after placing the new dentures.
      The treatment outcome was assessed in a group of 26 head neck cancer patients who
      were subjected to radiotherapy after tumour surgery. Standardized questionnaires
      were completed and clinical and radiographic assessments were performed. After
      randomization, endosseous Branemark implants were placed in the anterior part of
      the mandible either under antibiotic prophylaxis (13 patients) or under
      antibiotic prophylaxis combined with pre and postsurgery hyperbaric oxygen (HBO)
      treatment (13 patients). In the HBO and non-HBO group eight implants (implant
      survival 85.2%) and three implants (implant survival 93.9%) were lost,
      respectively. Peri-implant tissues had a healthy appearance in both groups.
      Osteoradionecrosis developed in one patient in the HBO group. All patients
      functioned well with their implant-retained lower denture. The quality of life
      related to oral functioning and denture satisfaction were improved to a
      comparable extent in the HBO and non-HBO group. Implant-retained lower dentures
      can improve the quality of life related to oral functioning and denture
      satisfaction in head and neck cancer patients. Adjuvant hyperbaric oxygen therapy
      could not be shown to enhance implant survival in radiated mandibular jaw bone.

PMID- 16996784
TI  - Knowledge and attitude towards risk factors in oral cancer held by dental
      hygienists in the Autonomous Community of Murcia (Spain): a pilot study.
AB  - The objective was to study the knowledge and attitude on risk factors in oral
      cancer held by dental hygienists working in private dental practices in the
      Autonomous Community of Murcia, Spain. An anonymous phone survey was made after
      obtaining consent from the interviewee. A simple randomized study was carried out
      and 240 dental hygienists were selected. The questionnaire was divided into three
      different parts: (1) professional data and years of practice; (2) knowledge of
      the risk factors in oral cancer and (3) education and training needs on oral
      cancer. The response rate was 58.3%. Regarding knowledge of the risk factors in
      oral cancer, 100% correctly identified tobacco and 90% alcohol, while only 50.7%
      identified sun exposure with labial cancer. Only 51.4% of the dental hygienists
      routinely gave advice to their patients on prevention of oral cancer.
      Furthermore, 57.1% did not consider themselves sufficiently well trained to
      discover suspected oral cancer lesions, and 84.3% recognized that their academic
      training on the early diagnosis and prevention of oral cancer was insufficient
      for their professional activity. To reduce morbidity and mortality of oral cancer
      it is necessary to implement training programs on oral cancer for dental
      hygienists, so they may acquire the necessary skills for its detection and
      prevention.

PMID- 16996785
TI  - Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF
      kappaB induction by safrole in human buccal mucosal fibroblasts.
AB  - Nuclear factor-kappa B (NF-kappaB) is considered to be important in many
      inflammatory and immune responses. The aim of this study was to compare NF-kappaB
      expression in normal human buccal mucosa and oral submucous fibrosis (OSF)
      specimens and further explore the potential mechanism that may lead to induction
      of NF-kappaB expression. Seventeen OSF and six normal buccal mucosa specimens
      were examined by immunohistochemistry. Primary human buccal mucosal fibroblasts
      (BMFs) were established and challenged with safrole, a major polyphenolic
      compound in the influorescence of Piper betel, by cytotoxicity and western blot
      assays. Furthermore, glutathione precursor N-acetyl-L-cysteine (NAC),
      extracellular signal-regulated protein kinase (ERK) inhibitor PD98059,
      cyclooxygenase-2 (COX-2) inhibitor NS-398, dexamethasone, and cyclosporin A were
      added to find the possible mechanism. NF-kappaB expression was significantly
      higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells,
      and inflammatory cells. Safrole was cytotoxic to BMFs in a dose-dependent manner
      (p<0.05). Western blot demonstrated highly elevated NF-kappaB protein expression
      in BMFs stimulated by safrole (p<0.05). In addition, pretreatment with
      pharmacological agents markedly inhibited the safrole induced-NF-kappaB
      expression (p<0.05). The result suggests that chewing areca quid may activate NF
      kappaB expression that may be involved in the pathogenesis of OSF. NF-kappaB
      expression induced by safrole in fibroblasts may be mediated by ERK activation
      and COX-2 signal transduction pathway.

PMID- 16996786
TI  - Adenoid cystic carcinoma of the buccal vestibule: A case report and review of the
      literature.
AB  - Minor salivary gland tumors of the buccal vestibule are relatively rare. Adenoid
      cystic carcinoma is the fifth most common salivary gland malignancy following
      mucoepidermoid carcinoma, adenocarcinoma not otherwise specified (NOS), acinic
      cell adenocarcinoma and polymorphous low-grade adenocarcinoma (PLGA). Greater
      than half of adenoid cystic carcinomas occur in the parotid and submandibular
      glands. The most common intraoral site is the palate. Adenoid cystic carcinoma
      tends to have a protracted clinical course with wide infiltration and late
      distant metastases. We present a case of an adenoid cystic carcinoma of the
      buccal vestibule in a 59-year-old Caucasian female patient that she had been
      aware of for 15 years.

PMID- 16996787
TI  - Systematic planning of patient records for cooperative care and multicenter
      research.
AB  - PURPOSE: The purpose of this paper is to introduce a method for systematically
      planning patient records for structured data entry that can be used in
      cooperative environments (e.g. cooperative care, multicenter trials) in a way
      that enables multipurpose use and shared data entry. METHODS: Design research,
      formal logic. RESULTS: The method suggests five steps: analyze the prevailing
      documentation infrastructure, provide terminology management system (TMS),
      provide documentation management system (DMS), plan the logical architecture,
      provide all necessary tools. CONCLUSIONS: The era of eHealth enables cooperative
      care and collaborative documentation. This can only be efficient if a multiple
      use and shared entry of data is realized. The task of the medical informatics
      community is to plan these environments systematically especially in complex
      environments which are enabled by emerging technologies.

PMID- 16996788
TI  - Identification of novel hepatitis C virus-specific cytotoxic T lymphocyte epiotpe
      in NS3 region.
AB  - Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) are thought to be
      effective in limiting viral spread and in clearing virus during infection.
      Therefore, we attempted to establish HCV-specific CTL and identify novel HCV
      specific CTL epitopes in a patient with acute hepatitis C by a novel screening
      method using recombinant vaccinia viruses (rVV) and synthetic peptides.
      CD8(+)CD45RA(-) T cells (memory T cells) were isolated from peripheral blood
      mononuclear cells (PBMC) of a patient with acute hepatitis C. HCV-specific CTL
      were cloned at limited dilutions and tested for HCV-specific CTL activity using a
      standard (51)Cr release assay. CTL assay was performed using rVV expressing
      regions of HCV-J, and overlapping and truncated synthetic peptides from HCV-J.
      CTL recognizing the NS3 region were isolated by (51)Cr release assay with rVV
      HCV. Isolated CTL were restricted by HLA class I molecules B(*)5603. We confirmed
      that isolated CTL recognized 8-mer amino acids in the NS3 region of HCV-J by
      (51)Cr release assay with overlapping and truncated synthetic peptides. In
      conclusion, we isolated HCV-specific CTL restricted by HLA-B(*)5603 and
      identified a novel HCV-specific CTL epitope (IPFYGKAI, amino acids 1373-1380) in
      the NS3 region. The identified HCV-specific CTL epitope might be useful for HCV
      therapy.

PMID- 16996789
TI  - Reverse ELISA for IgG and IgM antibodies to detect Lassa virus infections in
      Africa.
AB  - BACKGROUND: Anti-Lassa antibodies are detected by indirect immunofluorescence
      assay (IFA) or by enzyme-immunoassay (ELISA). Both methods have problems to
      detect low amounts of specific antibodies. OBJECTIVES: We report here highly
      sensitive and specific reverse ELISAs to detect Lassa virus IgG and IgM
      antibodies. Due to the reverse techniques, serum samples could be applied at
      dilutions of 1:10 without increasing non-specific background reactions. STUDY
      DESIGN: For IgM antibody detection microtiter plates were coated with anti-IgM
      antibodies and for IgG antibody detection with rheumatoid factor (RF) (Sachers M,
      Emmerich P, Mohr H, Schmitz H. Simple detection of antibodies to different
      viruses using rheumatoid factor and enzyme-labelled antigen (ELA). J Virol
      Methods 1985;10:99-110). In both assays a tissue culture antigen was used in
      combination with a labeled anti-Lassa monoclonal antibody (Hufert FT, Ludke W,
      Schmitz H. Epitope mapping of the Lassa virus nucleoprotein using monoclonal anti
      nucleocapsid antibodies. Arch Virol 1989;106(3-4):201-12). RESULTS: The reverse
      ELISA turned out to detect virus-specific IgG and IgM antibody in all 20 samples
      of West African patients collected 2-8 weeks after onset of Lassa fever.
      Moreover, both IFA and reverse ELISA found IgG antibodies in 53 out of 643
      samples of healthy West Africans (sensitivity of 100%). Six of the 643 samples
      were positive by reverse IgG ELISA only. Thus, the specificity compared to IIF
      was 99.0%, but it may be even higher, because compared to IFA the IgG ELISA was
      clearly more sensitive in detecting low antibody titers. CONCLUSIONS: In Ghana 3%
      seropositives were found by IFA, but 4% by the reverse ELISA. The reverse ELISAs
      can be performed with high sensitivity and specificity under field conditions in
      Africa.

PMID- 16996790
TI  - Characterization of an astrovirus genotype 2 strain causing an extensive outbreak
      of gastroenteritis among Maxakali Indians, Southeast Brazil.
AB  - BACKGROUND: Human astroviruses (HAstVs) are a common cause of sporadic diarrhea
      in children but large outbreaks occur in children's day care centers, schools and
      in homes for the elderly. OBJECTIVES: To report a large outbreak of acute
      gastroenteritis that occurred in January 2004 among Indians from the Maxakali
      Reserve in the State of Minas Gerais, Brazil. STUDY DESIGN: Fecal samples from 46
      Maxakali patients were collected and tested for a range of enteric pathogens.
      HAstVs was detected by EIA and strains were confirmed by RT-PCR and typed by
      direct sequencing. Clinical information was collected. RESULTS: The illness which
      affected more than 100 children under 6 years of age was characterized by watery
      diarrhea, fever and vomiting. HAstV-2 was the sole enteropathogen detected in 26
      (56%) of 46 samples analyzed by EIA and/or RT-PCR. The 17 positive samples
      sequenced were identical in a 348bp region used for phylogenetic analysis and
      were classified as genotype 2. CONCLUSIONS: This is the first description of an
      outbreak of HAstV-2 gastroenteritis in a population of Brazilian Indians. The
      magnitude of the outbreak and the severity of the disease underscore the need to
      better understand the epidemiology of astrovirus and other enteric agents in
      these populations.

PMID- 16996791
TI  - Prevalence and molecular characterization of human group C rotaviruses in
      Hungary.
AB  - BACKGROUND: Group C rotaviruses are recognized enteric pathogens of humans and
      animals. Human group C rotaviruses have been associated with sporadic episodes
      and large outbreaks of gastroenteritis in children and adults but their
      epidemiology and ecology are still unexplored. OBJECTIVES: To collect
      epidemiological data on group C rotavirus infections among children with
      gastroenteritis in Hungary and perform molecular characterization on the
      identified strains. STUDY DESIGN: Fecal samples were collected during the 2003
      surveillance in Baranya County, Hungary. The presence of group C rotavirus RNA
      was investigated by polyacrylamide gel electrophoresis and by reverse
      transcription-nested polymerase chain reaction for the VP6 gene. The identified
      strains were further characterized by sequencing and phylogenetic analysis of the
      VP7, VP6, VP4, and NSP4 genes. RESULTS: Three of 472 samples (0.6%) tested
      positive for group C rotavirus. Two samples were selected for molecular analysis.
      Strains BaC 6104/03 and BaC 11549/03 displayed an overall identity of >99.8% and
      99.3% at the nucleotide and amino acid level, respectively. The VP7 of the strain
      BaC 6104/03 was most closely related (99.5% aa) to the Nigerian strain Jajeri,
      while the VP4s of strains BaC 6104/03 and BaC 11549/03 were more similar (98.1%
      aa) to strains Belem and 208, detected in Brazil and China, respectively.
      CONCLUSIONS: Based on this 1-year study, we conclude that group C rotaviruses are
      not of epidemiological relevance in the etiology of childhood acute
      gastroenteritis in Hungary. The low sequence divergence between the Hungarian
      strains suggested that a single group C rotavirus strain circulated in this
      period in the study area.

PMID- 16996792
TI  - Serum procalcitonin levels in chronic hepatitis C patients under pegylated
      interferon-alpha plus ribavirin treatment.
AB  - OBJECTIVES: To evaluate the alterations of serum procalcitonin (PCT) levels in
      patients with chronic hepatitis C during pegylated interferon-alpha (PEG-IFNa)
      plus ribavirin (RIB) treatment and to correlate them with clinical and
      virological outcomes. STUDY DESIGN: Fifty-two consecutive patients (29 males,
      age=41.2+/-14.7 years) with chronic HCV-related liver disease (six cirrhotics)
      were evaluated for PCT levels at baseline and during the treatment course (at
      week 12, 24, 48 and 72) with PEG-IFNa plus RIB. Sustained virological response
      (SVR) was confirmed by undetectable serum HCV-RNA at the end of treatment and
      again 6 months after completion of treatment. RESULTS: Two patients exhibited
      culture-proved bacterial infections during the treatment course. Thirty-six
      patients (69.2%) exhibit SVR and 16 (30.8%) were non-responders. Serum PCT levels
      remained within normal limits (0.1-0.5 ng/mL) in all treated patients throughout
      the follow-up period except those two who exhibited bacterial infections during
      the treatment course. Virological responders exhibited significant decline of
      serum PCT levels over time compared to non-responders (p<0.001), even when
      adjusted for multiple baseline parameters (p=0.037). CONCLUSION: Serum PCT levels
      decline in chronic hepatitis C patients during PEG-IFNa plus RIB treatment,
      especially in the sustained virological responder group, while they elevate only
      when bacterial infections complicate the treatment course.

PMID- 16996793
TI  - Not polymorphism but methylation of class II transactivator gene promoter IV
      associated with persistent HBV infection.
AB  - BACKGROUND: Class II transactivator (CIITA) is the major rate-limiting regulator
      for expression of class II major histocompability complex (MHC-II). Human CIITA
      gene expression is controlled by four distinct promoters (pIto pIV). OBJECTIVE:
      To evaluate the relationship among polymorphism and methylation status of CIITA
      gene promoters and persistent hepatitis B virus (HBV) infection. METHODS: We
      recruited 21 patients with hepatocellular carcinoma (HCC), 45 liver cirrhosis
      (LC), 65 chronic hepatitis B (CHB), 26 acute hepatitis B (AHB) and 95 healthy
      blood donors. Polymorphism of CIITA gene promoters was assayed by PCR-SSCP
      sequencing. Bioinformatics analysis was employed to predict the existence of CpG
      islands. Methylation-specific PCR (MSP) was used to detect the methylation status
      of CIITA gene pIV. RESULTS: No sequence differences were observed at CIITA genes
      pI, III and IV among HCC, LC, CHB, AHB patients and healthy controls. No CpG
      islands were found in the pI, pII and pIII sequences, but there was a CpG island
      in pIV. The frequency of methylated POV was not significantly different within
      persistent HBV infection groups (patients with HCC, LC or CHB). Significance was
      found between the persistent infection group and acute HBV infection or healthy
      controls. CONCLUSIONS: CIITA gene promoter sequences are conserved. PIV is highly
      methylated and associated with host susceptibility to HBV persistent infection.

PMID- 16996794
TI  - Cholesterol loading increases the translocation of ATP synthase beta chain into
      membrane caveolae in vascular endothelial cells.
AB  - Caveolae and its structural protein caveolin-1 (Cav-1) are abundant in vascular
      endothelial cells (ECs) and have been suggested to contribute to cell signaling
      and cholesterol trafficking. This study investigated the effect of cholesterol on
      the movement of caveolae-related proteins in human umbilical vein ECs with use of
      caveolae functional proteomics. After cholesterol exposure to ECs for 2 to 4 h,
      caveolae were isolated and separated on 2-D protein gels. Among 40 protein spots
      revealed in caveolae fractions, the ATP synthase beta subunit (ATPS-beta), one of
      the 3 proteins enriched by cholesterol in caveolae, was confirmed by western
      blotting and confocal microscopy. Further, cholesterol exposure increased the
      level of ATPS-beta, along with Cav-1 and cholesterol in caveolae. These effects
      could be blocked by cytochalasin B, an actin cytoskeleton disruptor. ATPS-beta
      was physically associated with Cav-1, as demonstrated by co-immunoprecipitation
      and GST-Cav-1 fusion protein pull-down assay. Cholesterol increased the
      extracellular ATP release mediated by ATPS-beta, since this action could be
      blocked by piceatannol or oligomycin, ATPS inhibitors. Thus, the ectopic
      localization of ATPS-beta may participate in the energy balance of cells in
      response to the change in intracellular cholesterol levels.

PMID- 16996795
TI  - Automatic lateralization of temporal lobe epilepsy based on scalp EEG.
AB  - OBJECTIVE: The objective of this work is the determination of the lateralization
      of the epileptic seizure onset zone using the scalp EEG signal processing.
      METHODS: A comprehensive method based on the evaluation of the evolution of the
      correlation coefficients computed between bipolar channels (longitudinal montage)
      was applied to 43 patients (87 seizures). The correlation coefficients are
      estimated by a nonlinear regression analysis. The methodology that leads to the
      lateralization is based on several processing steps: segmentation, seizure onset
      determination and then lateralization. RESULTS: Results show that the mean level
      of the nonlinear correlation values computed between EEG channels at the seizure
      onset time is significantly higher on the side of the beginning of a seizure.
      CONCLUSIONS: The side of the seizure onset was determined for about 80-90% of the
      seizures studied with a satisfactory high reproducibility level. SIGNIFICANCE:
      Comparison of nonlinear correlation coefficients between both sides of the brain
      leads to the determination of the side of seizure onset.

PMID- 16996796
TI  - The long thoracic nerve conduction study revisited in 2006.
AB  - OBJECTIVE: To compare the reliability and feasibility of recording long thoracic
      nerve (LTN) conductions either with surface or needle electrodes. METHODS: The
      nerve conduction studies were carried out bilaterally on 40 control subjects. The
      LTN was first stimulated at the axilla and recorded with surface electrodes
      located on the 7th or 8th digitations of the serratus anterior (SA), then
      stimulated at Erb's point and recorded with a needle inserted in the 6th or 7th
      digitations of the SA. For each method, the latency and amplitude of the motor
      action potential were recorded. RESULTS: Responses were recorded on both sides
      for each patient. With surface recording, the mean latency was 2.2 +/- 0.30 ms,
      and the mean amplitude was 5.3 +/- 2.4 mV. With needle recording, the mean
      latency was 3.65 +/- 0.45 ms, and the mean amplitude was 8.95 +/- 4 mV.
      CONCLUSIONS: This study demonstrates that both techniques are reliable, feasible,
      and correlate well. SIGNIFICANCE: Our study shows surface recording of nerve
      conduction should be favored because it is non-traumatic, less uncomfortable for
      the patient, and less prone to pitfalls. Nevertheless, in pathological cases,
      both techniques should be used at initial and follow-up examinations in order to
      better assess axonal loss and nerve conduction impairment.

PMID- 16996797
TI  - Updating motor unit number estimation (MUNE).
AB  - Motor unit number estimation (MUNE) is a unique electrophysiologic technique that
      can provide a numeric estimate of the number of axons innervating a muscle or
      group of muscles. The first technique was first described in 1971, and since then
      different techniques have been developed to address specific methodologic issues.
      The field was reviewed in this journal in 2001, and this update covers new
      information and uses of MUNE over the past five years. These include models of
      muscles that allow evaluation of MUNE techniques and comparisons between
      techniques. There have been further investigations of specific technical aspects
      of MUNE. Modifications to MUNE techniques have been offered that permit more
      rapid acquisition of data. MUNE has been used in clinical situations to elucidate
      the pathophysiology features of axonal loss in a number of disorders. There is
      now more experience with MUNE as endpoint measures in clinical trials.

PMID- 16996798
TI  - Increased nodal persistent Na+ currents in human neuropathy and motor neuron
      disease estimated by latent addition.
AB  - OBJECTIVE: To investigate the changes in nodal persistent Na(+) currents in human
      neuropathy and motor neuron disease. In human motor axons, approximately 1.0% of
      total Na(+) channels are active at rest, termed "persistent" Na(+) channels, and
      the conductance can be non-invasively estimated by the technique of latent
      addition in vivo. METHODS: Latent addition was performed in median motor axons of
      93 patients with axonal neuropathy (n=38), lower motor neuron disorder (LMND;
      n=19) or amyotrophic lateral sclerosis (ALS; n=36) and in 27 age-matched normal
      subjects. Brief hyperpolarizing conditioning current pulses were delivered, and
      threshold change at the conditioning-test interval of 0.2 ms was measured as an
      estimator of the magnitude of persistent Na(+) currents. Threshold electrotonus
      and supernormality were also measured as indicators of resting membrane
      potential. RESULTS: Threshold changes at 0.2 ms were significantly greater in
      patients with neuropathy or LMND (p<0.05), and tended to be greater in ALS
      patients (p=0.075) than in normal controls. Threshold electrotonus and
      supernormality did not differ in each patient group and normal controls,
      suggesting that membrane potential is not altered in patients. In the recovery
      phase of axonal neuropathy, the threshold changes increased in parallel with an
      increase in amplitudes of compound muscle action potential. CONCLUSIONS:
      Persistent Na(+) currents appear to increase commonly in disorders involving
      lower motor neurons, possibly associated with axonal regeneration or collateral
      sprouting or changes in Na(+) channel gating. SIGNIFICANCE: The increased axonal
      excitability could partly be responsible for positive motor symptoms such as
      muscle cramping frequently seen in lower motor neuron disorders.

PMID- 16996799
TI  - Respiratory and cardiovascular functions among smoking and nonsmoking girls from
      two regions with different air pollution degree.
AB  - AIM: The aim of the present study was to analyze the respiratory and
      cardiovascular functions among smoking and nonsmoking girls attending two schools
      situated in regions with different levels of air pollution. The characteristic of
      air pollution is based on the data gathered by stations 1 and 2 belonging to the
      Uniform National System for Monitoring the Air Pollution in Bulgaria. The
      participants (n=108, 16.07+/-0.80 years) were separated in two groups: smokers
      (S1 - from school 1, S2 - from school 2) and nonsmokers (NS1 - from school 1, NS2
      - from school 2). All of them performed pulmonary function testing and
      .cardiopulmonary exercise testing on a treadmill using our modification of the
      Balke protocol (Marinov et al., 2000). Reference values for European children,
      previously validated for the Bulgarian population, were used. RESULTS: There are
      no significant differences in mean levels of VC, IC, FEV1, MEF50 and MEF25 (as a
      percentage from the predicted value as well). The average level of the Tiffneau
      index is noticeably higher among nonsmokers from the two regions and is the
      lowest among smokers from the more polluted area, but a significant difference
      exists between S2 (88.7+/-5.9) and NS2 (92.6+/-4.7), p=0.047; T(L,CO)%pred: S1
      (85.4+/-7.2) vs. S2 (86.7+/-8.2), p=0.048 and NS1 (88.3+/-8.2) vs. NS2 (92.8+/
      14.5), p=0.037; V(E)%pred: S1 (127.5+/-9.6) vs. S2 (123.7+/-6.1), p=0.035; higher
      levels of total lung capacity (TLC%pred), S1 (107.3+/-9.2) vs. NS2 (104.3+/-9.1),
      p=0.009 and alveolar ventilation (VA), S1 (5.0+/-0.6) vs. NS2 (4.6+/-0.5),
      p=0.008. CONCLUSIONS: 1. The negative effects of the combined influence of
      tobacco smoking and air pollution on some respiratory and cardiovascular
      functions of adolescent girls are more pronounced than each influence alone. 2.
      The cardiopulmonary exercise test gives adequate information about the combined
      effect of air pollution and smoking and using it for preventive purposes is an
      advisable method.

PMID- 16996800
TI  - TRPV1: a therapeutic target for novel analgesic drugs?
AB  - The vanilloid receptor TRPV1 is now recognized as a molecular integrator of
      painful stimuli ranging from noxious heat to endovanilloids in inflammation.
      Pharmacological blockade of TRPV1 represents a new strategy in pain relief. TRPV1
      antagonists are expected to prevent pain by silencing receptors where pain is
      generated rather than stopping the propagation of pain, as most-traditional pain
      killers do. This hypothesis has already being tested in the clinic by
      administering small molecule TRPV1 antagonists (e.g. GlaxoSmithKline SB-705498)
      for migraine and dental pain. Paradoxically, in some murine models of chronic
      pain, TRPV1-deficient mice exhibit more pain-related behavior than their wild
      type littermates, indicating that the understanding of TRPV1 in pain is still
      incomplete. Moreover, there is mounting evidence to suggest the existence of
      functional TRPV1 both in the brain and in various non-neuronal tissues. The
      biological role of these receptors remains elusive, but their tissue distribution
      clearly indicates that they are involved in many more functions than just pain
      perception. Here, we review the potential therapeutic indications and adverse
      effects of TRPV1 antagonists.

PMID- 16996801
TI  - PTEN in the haematopoietic system and its therapeutic indications.
AB  - A unique feature of the haematopoietic system is its self-renewal ability while
      maintaining a stable number of pluripotent haematopoietic stem cells (HSCs).
      Recently, two publications by Yilmaz and colleagues and Zhang and colleagues
      demonstrated that the loss of the tumour suppressor phosphatase and tensin
      homolog (PTEN) in mice disturbed the maintenance of quiescent HSCs and promoted
      leukemogenesis. Mammalian target of rapamycin (mTOR) inhibition with rapamycin
      distinctly rescued HSC development and depleted leukemic stem cells. Thus, the
      regulation of HSCs and leukemic cells seems to be governed by cell-context
      dependent, PTEN-mediated regulation of mTOR.

PMID- 16996802
TI  - Subjective somnolence relates mainly to depression among patients in a tertiary
      care epilepsy center.
AB  - Many patients with epilepsy complain of decreased energy and somnolence. There is
      increased awareness that comorbidity, especially depression, plays an important
      role in determining the quality of life for patients with epilepsy. We set out to
      determine how subjective somnolence is affected by depression, age, hours of
      sleep, sleep apnea, seizure frequency, and numbers of antiepileptic drugs and
      central nervous system drugs. A questionnaire and chart review were used to
      investigate patients in a tertiary referral center. We found that subjective
      somnolence was prominent and that it relates mainly to depression, less to
      obstructive sleep apnea, and not to the other variables. Further investigation is
      needed into the relationship between depression and subjective somnolence in
      patients with epilepsy.

PMID- 16996803
TI  - Endoscopic ultrasound-guided fine needle aspirate microsatellite loss analysis
      and pancreatic endocrine tumor outcome.
AB  - BACKGROUND & AIMS: The clinical course of pancreatic endocrine tumor (PET) varies
      depending on tumor aggressiveness, disease extent, and possibly accumulated
      molecular alterations. Endoscopic ultrasound-guided fine-needle aspiration (EUS
      FNA) results, although accurate in diagnosing PET, correlate poorly with PET
      outcome. The role of detecting key molecular abnormalities in predicting PET
      behavior and clinical outcome from EUS-FNA material remains unknown. METHODS:
      Patients with confirmed PET who underwent EUS-FNA during a 32-month period were
      included. Patient demographics and clinical data were recorded and follow-up
      information was obtained by contacting their physician to evaluate disease
      progression. Representative tumor cells were microdissected from the FNA
      material. DNA was harvested and amplified, targeting a panel of 17 polymorphic
      microsatellite markers on chromosomes 1p, 3p, 5q, 9p, 10q, 11q, 17p, 17q, 21q,
      and 22q. The polymerase chain reaction products were subjected to fluorescent
      capillary gel electrophoresis to detect microsatellite loss. The fractional
      allelic loss (FAL) was calculated. RESULTS: Twenty-five patients were studied.
      Thirteen were classified histologically as benign PET limited to the pancreas and
      12 as malignant PET (invasive or metastatic). The mean FAL in the benign and
      malignant PET was 0.03 and 0.37 (P<.0001), respectively. In addition, the mean
      FAL was significantly greater in those with disease progression as compared with
      patients with stable disease (0.45 vs 0.09 respectively, P<.0001). CONCLUSIONS:
      Microsatellite loss analysis of EUS-FNA material from PET can be performed
      reliably and an FAL value of more than 0.2 is associated with disease
      progression. This technique may have value in the preoperative assessment and
      risk stratification of patients with PET.

PMID- 16996804
TI  - Colorectal cancers found after a complete colonoscopy.
AB  - BACKGROUND & AIMS: The incidence of colorectal cancer in patients undergoing
      colonoscopic surveillance is higher than previously thought. A better
      understanding of interval cancers is needed to improve surveillance strategies.
      The objectives of this study were to determine whether interval colorectal
      cancers were associated with an inadequate earlier colonoscopy, incomplete
      polypectomy, or aggressive biologic behavior. METHODS: We searched our
      institution's cancer registry. Interval cancers were defined as colorectal
      cancers that developed within 5 years of a complete colonoscopy. These were
      frequency matched in a 1:2 ratio to patients with sporadic cancers, which were
      defined as colorectal cancers diagnosed on a patient's first recorded
      colonoscopy. Patient, colonoscopy, and tumor characteristics of interval and
      sporadic cancers were compared. RESULTS: Of the 830 colorectal cancers diagnosed
      during the study period, 45 patients developed an interval cancer (5.4%; 95%
      confidence interval, 4.1%-7.2%). Twenty-seven percent of interval cancers
      developed at previous polypectomy segments, and location of polypectomy segments
      was predictive of the location of subsequent interval cancers. Interval cancers
      were 3 times more likely to occur in the right colon and were smaller in size
      than sporadic cancers. Quality of bowel preparation, individual endoscopist,
      endoscopist experience, and trainee involvement were not associated with interval
      cancers. No difference in TNM stage at diagnosis, histologic type or grade,
      carcinoembryonic antigen level, or 5-year survival was found between interval and
      sporadic cancers. CONCLUSIONS: Incomplete polypectomy might play an important
      role in the development of interval colorectal cancer. No association between
      other colonoscopy-related factors or tumor characteristics and interval cancers
      was found.

PMID- 16996805
TI  - Urine PGE-M: A metabolite of prostaglandin E2 as a potential biomarker of
      advanced colorectal neoplasia.
AB  - BACKGROUND & AIMS: The enzyme cyclooxygenase-2 is expressed in a majority of
      colorectal carcinomas (CRCs) and is important in prostaglandin production. We
      have developed an accurate method to measure the urinary metabolite of
      prostaglandin E(2) (PGE-M) using recently developed mass spectrometric
      techniques. The purpose of this pre-validation study was to determine if urinary
      PGE-M levels can be used as a biomarker to discriminate between healthy patients
      and those with colorectal disease. METHODS: Urine PGE-M was assessed in a total
      of 228 patients with CRC, colonic adenomatous polyps, Crohn's disease, and in
      subjects with no endoscopically detectable disease. Thirteen rectal carcinoma
      patients were treated with celecoxib and urinary PGE-M was measured before and
      after treatment. RESULTS: Urine PGE-M levels were increased among healthy men
      compared with healthy women (median, 8.59 [interquartile range (IQR), 5.67-22.3]
      vs 4.25 [IQR, 2.35-6.03], P = .0027). Urine PGE-M levels among patients with
      Crohn's disease (median, 19.85 [IQR, 6.89-90.2]), CRC (median, 14.65 [IQR, 5.94
      92.1]), or large adenomas greater than 1 cm in size (median, 18.85 [IQR, 11.9
      25.6]) were significantly increased when compared with patients who had either
      small polyps less than 1 cm in size (median, 9.69 [IQR, 6.41-22.2]), or no polyps
      (median, 7.05 [IQR, 2.35-24.7]) (P = .0001). PGE-M levels decreased significantly
      after celecoxib treatment in patients with rectal cancer (median, 21.7 [IQR, 16.2
      29.9] vs 9.14 [IQR, 7.14-13.2], P = .009). CONCLUSIONS: The increase in urinary
      PGE-M in patients with colorectal cancers and large adenomas suggests that
      urinary PGE-M is a potentially useful biomarker for the detection of advanced
      colorectal neoplasia.

PMID- 16996806
TI  - Influence of high body mass index on outcome in acute liver failure.
AB  - BACKGROUND & AIMS: Diabetes and obesity affect development of nonalcoholic fatty
      liver disease. Nonalcoholic fatty liver disease increases susceptibility to
      hepatic injury and limits regenerative capacity, which might increase adverse
      outcomes in acute liver failure. There is no difference in the prevalence of
      diabetes in acute liver failure patients when compared with the general
      population, but no large studies have examined the relationship of obesity to
      incidence or outcome of acute liver failure. METHODS: Seven hundred eighty-two
      adult patients with acute liver failure were prospectively enrolled from 1998
      2004. Body mass index, history of diabetes, and outcome were recorded.
      Multivariable logistic regression was used for the analysis. RESULTS: Compared
      with 30.4% of adults in the National Health and Nutrition Examination Survey III,
      29.1% of adult patients with acute liver failure were obese (P=.542). Obese
      patients had 1.63 times the odds of transplantation or death as nonobese patients
      (1.04-2.55, P=.033). Severely obese patients had 1.93 times the odds of
      transplantation or death (1.02-3.62, P=.042). There were no differences in the
      proportion of patients listed for transplantation, with body mass index greater
      or less than 30, 35, or 40 (P=.264, P=.112, P=.244, respectively). Obese patients
      had 3.4 times the odds of dying after transplantation (1.29-8.87, P=.01).
      CONCLUSIONS: Obesity does not appear to be more prevalent in acute liver failure.
      However, obese and severely obese patients had significantly poorer outcomes when
      they developed acute liver failure. This difference is not explained by weight
      discrimination in listing patients for transplantation, despite evidence for
      poorer post-transplant outcomes.

PMID- 16996807
TI  - Primary malignant melanoma of the right colon.

PMID- 16996808
TI  - The Take Control of Your Blood pressure (TCYB) study: study design and
      methodology.
AB  - BACKGROUND: Among the 65 million Americans with hypertension, only approximately
      31% have their blood pressure under control (<140/90 mm/Hg). Despite the damaging
      impact of hypertension and the availability of evidence-based target values for
      blood pressure, interventions to improve blood pressure control have had limited
      success. OBJECTIVES: A randomized controlled health services intervention trial
      with a two by two design is being conducted to improve blood pressure control.
      This five-year trial evaluates two patient-directed interventions designed to
      improve blood pressure control among patients diagnosed with hypertension in a
      community-based primary care setting. METHODS: Patients are randomized to one of
      four groups: usual care, home blood pressure monitoring, tailored behavioral self
      management intervention that is administered via telephone by a nurse, or a
      combination of the home blood pressure monitoring and tailored behavioral
      intervention. Patients receiving the home blood pressure monitoring are trained
      in the use of an electronic blood pressure measurement device, are asked to
      measure their blood pressure 3 times/week, and send in two-month blood pressure
      recordings throughout the 24-month study duration. The behavioral intervention
      incorporates patients' need assessments and involves tailored behavioral and
      education modules to promote medication adherence and improve specific health
      behaviors. A nurse delivers all behavioral self-management modules over the
      telephone bi-monthly for 24 months. The primary outcome is the proportion of
      patients who achieve control of their blood pressure based on evidence-based
      guidelines (for patients without diabetes <140/90 mm/Hg, for patients with
      diabetes <130/80 mm/Hg) evaluated at six-month intervals over 24 months (five
      measurements) using a random-zero sphygmomanometer. CONCLUSION: Despite the known
      risk of poor blood pressure control, and the wide availability of effective
      treatment strategies, a majority of adults still do not have their blood pressure
      controlled. This study will be an important step in defining two explicit
      interventions to improve blood pressure control. To our knowledge, this study is
      the first to combine both a tailored behavioral self-management intervention and
      self-monitoring home blood pressure intervention to improve blood pressure
      control among patients in a primary care setting.

PMID- 16996809
TI  - Role of a MutY DNA glycosylase in combating oxidative DNA damage in Helicobacter
      pylori.
AB  - MutY is an adenine glycosylase that has the ability to efficiently remove
      adenines from adenine/7,8-dihydro-8-oxoguanine (8-oxo-G) or adenine/guanine
      mismatches, and plays an important role in oxidative DNA damage repair. The human
      gastric pathogen Helicobacter pylori has a homolog of the MutY enzyme. To
      investigate the physiological roles of MutY in H. pylori, we constructed and
      characterized a mutY mutant. H. pylori mutY mutants incubated at 5% O2 have a 325
      fold higher spontaneous mutation rate than its parent. The mutation rate is
      further increased by exposing the mutant to atmospheric levels of oxygen, an
      effect that is not seen in an E. coli mutY mutant. Most of the mutations that
      occurred in H. pylori mutY mutants, as examined by rpoB sequence changes that
      confer rifampicin resistance, are GC to TA transversions. The H. pylori enzyme
      has the ability to complement an E. coli mutY mutant, restoring its mutation
      frequency to the wild-type level. Pure H. pylori MutY has the ability to remove
      adenines from A/8-oxo-G mismatches, but strikingly no ability to cleave A/G
      mismatches. This is surprising because E. coli MutY can more rapidly turnover A/G
      than A/8-oxo-G. Thus, H. pylori MutY is an adenine glycosylase involved in the
      repair of oxidative DNA damage with a specificity for detecting 8-oxo-G. In
      addition, H. pylori mutY mutants are only 30% as efficient as wild-type in
      colonizing the stomach of mice, indicating that H. pylori MutY plays a
      significant role in oxidative DNA damage repair in vivo.

PMID- 16996810
TI  - Development of an at-line method for the identification of angiotensin-I
      inhibiting peptides in protein hydrolysates.
AB  - A fast at-line method was developed for the identification of ACE inhibiting
      (ACEI) peptides in protein hydrolysates. The method consists of activity
      measurements of fractions collected from a two-dimensional HPLC fractionation of
      the peptide mixture followed by MS identification of the peptides in the
      inhibiting fractions. The inhibition assay is based on the inhibiting effect of
      ACEI peptides on the hydrolytic scission of the substrate Hippuric acid-His-Leu
      (HHL) during the ACE-catalysed hydrolysis reaction. A fast LC method was
      developed for the quantification of Hippuric acid (H) and Hippuric acid-Histidine
      Leucine (HHL), allowing a large number of fractions to be analysed within a
      reasonable time period. The method is sensitive and uses only standard laboratory
      equipment. The limit of detection is 0.34 microM for the known ACEI peptide IPP.
      This is sufficiently sensitive for the identification of only moderately active
      peptides and/or ACEI peptides present at low concentrations. The relative
      standard deviation of the inhibition assay was 12% measured over a time period of
      2 months. The IC50 value of IPP measured with the assay was 5.6 microM, which is
      comparable to the values of 5 microM and 5.15 microM reported in literature for
      the standard Matsui method. The assay was successfully applied in the
      identification of ACEI peptides in enzymatically hydrolysed caseinate samples.
      Two new, not earlier published ACEI peptides were identified; MAP (beta-casein
      f102-104) and ITP (alpha-s2-casein f119-121) with IC50 values of 3.8 microM and
      50 microM, respectively.

PMID- 16996811
TI  - Development of a fingerprint of Salvia miltiorrhiza Bunge by high-performance
      liquid chromatography with a coulometric electrode array system.
AB  - To standardize and control herbal medicines, a feasible approach and control
      system is necessary. In this paper, a high-performance liquid chromatography with
      a coulometric electrode array detector (HPLC-CEAD) system was applied to
      fingerprint Salvia miltiorrhiza Bunge (S. miltiorrhiza Bunge), a popular herbal
      medicine, for the first time. pH of mobile phase, working potentials and sample
      preparation were included in our research. Twenty-five common peaks were obtained
      from extracts of S. miltiorrhiza Bunge (Shandong province), more than that
      obtained in previous report. Fingerprints of S. miltiorrhiza Bunge from different
      locations were also studied. The content of main components varied in different
      samples. Overlapping ratio of peaks (ORP) in 10 batches of S. miltiorrhiza Bunge
      (Shandong province) was not less than 72.46%. In method validation, relative
      standard deviation (RSD) of relative retention times and relative peak areas were
      of not more than 3%. It was concluded that HPLC-CEAD system can be applied in
      fingerprinting herbal medicines.

PMID- 16996812
TI  - Redesign of human carbonic anhydrase II for increased esterase activity and
      specificity towards esters with long acyl chains.
AB  - The effect of modulating the shape and the size of the hydrophobic pocket on the
      esterase activity and specificity of human carbonic anhydrase II (HCAII) for
      esters with different acyl chain lengths was investigated. Following an initial
      screen of 7 HCAII variants with alanine substitutions in positions 121, 143 and
      198, detailed kinetic measurements were performed on HCAII and the variants
      V121A, V143A and V121A/V143A. For some variants, an increased size of the
      hydrophobic pocket resulted in increased activities and specificities for longer
      substrates. For V121A/V143A, the rate of hydrolysis for paranitrophenyl valerate
      was increased by a factor of approximately 3000. The specificities also changed
      dramatically, for example V121A/V143A is 6.3 times more efficient with
      paranitrophenyl valerate than paranitrophenyl acetate, while HCAII is >500 times
      more efficient with paranitrophenyl acetate than paranitrophenyl valerate. An
      automated docking procedure was performed on these variants with transition state
      analogues (TSAs) for the hydrolysis reaction. It was possible to correlate the
      catalytic rate constants to the docking results, i.e. for each variant, efficient
      hydrolysis was generally correlated to successful TSA-docking. The observations
      in this paper show that the redesign increased the catalytic rates for substrates
      with long acyl chains by removal of steric hinders and addition of new favourable
      binding interactions.

PMID- 16996813
TI  - Eosinophil chemotactic factor-L (ECF-L) enhances osteoclast formation by
      increasing in osteoclast precursors expression of LFA-1 and ICAM-1.
AB  - ECF-L is a novel autocrine stimulator of osteoclast (OCL) formation that enhances
      the effects of 1,25-(OH)2D3 and RANK ligand (RANKL) and is increased in
      inflammatory conditions such as rheumatoid arthritis. ECF-L acts at the later
      stages of OCL formation and does not increase RANKL expression. Thus, its
      mechanism of action is unclear. Therefore, RAW 264.7 cells and M-CSF-dependent
      murine bone marrow macrophage (MDBM) cells were treated with RANKL and/or with
      recombinant ECF-L expressed as a Fc fusion protein (ECF-L-Fc) to determine their
      effects on NF-kappaB, AP-1 and JNK activity, and on the expression of the
      adhesion molecules that have been implicated in OCL formation. These parameters
      were measured by semiquantitative and PCR and Western blot analysis. In addition,
      the role of ICAM-1 was further assessed by treating normal mouse marrow cultures
      with ECF-L-Fc and 10(-10) M 1,25-(OH)2D3 in the presence or absence of a blocking
      ICAM-1 antibody or treating marrow cultures from ICAM-1 knockout mice with ECF-L
      and 1,25-(OH)2D3. ECF-L-Fc by itself only modestly increased NF-kappaB binding
      and JNK activity in RAW 264.7 cells, which was further enhanced by RANKL. In
      contrast, ECF-L-Fc increased LFA-1alpha and ICAM-1 mRNA levels 1.8-fold in mouse
      marrow cultures, and anti-ICAM-1 almost completely inhibited OCL formation
      induced by 10(-10) M 1,25-(OH)2D3 and ECF-L. Furthermore, ECF-L did not increase
      OCL formation in marrow cultures from ICAM-1 knockout mice. Taken together, these
      results demonstrate that ECF-L enhances RANKL and 1,25-(OH)2D3-induced OCL
      formation by increasing adhesive interactions between OCL precursors through
      increased expression of ICAM-1 and LFA-1.

PMID- 16996814
TI  - A "STEP" in the right direction.

PMID- 16996815
TI  - A step towards more ethical prayer studies.

PMID- 16996816
TI  - WATCHMAN: an effective protection against stroke?

PMID- 16996818
TI  - Letter to the editor by Dr. Adam H. Skolnick.

PMID- 16996819
TI  - Controlling the independent variables in the clinical study of prayer: the devil
      is in the details.

PMID- 16996820
TI  - There is still hope for multifaceted intervention in heart failure.

PMID- 16996822
TI  - Acute coronary syndromes in young patients with angiographically normal coronary
      arteries.

PMID- 16996823
TI  - Potential for improving sensitivity for detection of old myocardial infarction
      using the Q wave equivalent criteria in the Selvester QRS scoring system.

PMID- 16996824
TI  - Broken bodies, broken hearts? Limitations of the trauma system as a model for
      regionalizing care for ST-elevation myocardial infarction in the United States.
AB  - Many cardiovascular experts have called for the creation of specialized
      myocardial infarction centers and networks in the United States analogous to the
      current model for major trauma. Patients suffering ST-elevation myocardial
      infarction (STEMI) and trauma share an essential feature that makes the argument
      for regionalization persuasive: rapid triage and treatment by highly trained
      personnel improve survival in both conditions. Despite this similarity, however,
      the trauma system may be limited as a model for regionalizing STEMI care. First,
      the development of trauma systems has been hindered by the struggle for
      sufficient and stable funding, competing interests among individual stakeholders,
      and the overall lack of desire for state-sponsored healthcare planning in the
      United States. These same obstacles would need to be overcome if STEMI care is
      regionalized. Second, unique characteristics related to STEMI care, such as its
      varied clinical presentation and more lucrative reimbursement, will create new
      challenges. In this article, we briefly review the current status of trauma
      systems in the United States and describe why the regionalization of STEMI care
      may require different methods of healthcare organization.

PMID- 16996825
TI  - Left bundle-branch block artifact on single photon emission computed tomography
      with technetium Tc 99m (Tc-99m) agents: mechanisms and a method to decrease false
      positive interpretations.
AB  - Myocardial perfusion scintigraphy is a well validated noninvasive method of
      evaluating for significant coronary artery disease, especially in cases where
      electrocardiographic changes are nondiagnostic, including left bundle-branch
      block. However, such testing with a technetium Tc 99m agent is often confounded
      by left ventricular septal-based false-positive perfusion defects. These defects
      can be either reversible or irreversible in the septal or anteroseptal wall,
      problematically then, in the territory supplied by the left anterior descending
      coronary artery. Mechanisms explaining false-positive defects include decreased
      perfusion via impaired microvessel flow and normal perfusion with apparent
      decrease in counts in a relatively thin septum (partial-volume effect). Key
      findings in myocardial perfusion images in the presence of left bundle-branch
      block that define true positives (ischemia) are reversible perfusion defects
      (especially at end diastole), a concomitant apical defect, and systolic
      dysfunction matching the perfusion defect.

PMID- 16996826
TI  - Evaluation of prasugrel compared with clopidogrel in patients with acute coronary
      syndromes: design and rationale for the TRial to assess Improvement in
      Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel
      Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38).
AB  - BACKGROUND: Dual antiplatelet therapy with aspirin and clopidogrel is standard
      for prevention of thrombotic complications of percutaneous coronary intervention
      (PCI). Prasugrel is a thienopyridine that is more potent, more rapid in onset,
      and more consistent in inhibition of platelets than clopidogrel. TRITON-TIMI 38
      is designed to compare prasugrel with clopidogrel in moderate to high-risk
      patients with acute coronary syndrome (ACS). STUDY DESIGN: TRITON-TIMI 38 is a
      phase 3, randomized, double-blind, parallel-group, multinational, clinical trial.
      Approximately 13,000 patients with moderate to high-risk ACS undergoing PCI (9500
      unstable angina/non-ST-segment elevation myocardial infarction [MI], 3500 ST
      segment elevation MI) will be randomized to prasugrel 60 mg loading dose followed
      by 10 mg daily or clopidogrel 300 mg loading dose followed by 75 mg daily for up
      to 15 months. The primary end point is the time of the first event of
      cardiovascular death, MI, or stroke. Analyses will be performed first in the
      unstable angina/non-ST-segment elevation MI cohort and, conditionally, on the
      whole ACS population. Major safety end points include TIMI major and minor
      bleeding unrelated to coronary artery bypass graft surgery. CONCLUSIONS: TRITON
      TIMI 38 is a phase 3 comparison of prasugrel versus clopidogrel in patients with
      moderate to high-risk ACS undergoing PCI. In addition, it is the first large
      scale clinical events trial to assess whether a thienopyridine regimen that
      achieves a higher level of inhibition of platelet aggregation than the standard
      therapy results in an improvement in clinical outcomes.

PMID- 16996827
TI  - Implantable defibrillator early after primary percutaneous intervention for ST
      elevation myocardial infarction: rationale and design of the Defibrillator After
      Primary Angioplasty (DAPA) trial.
AB  - BACKGROUND: It has been shown that an implantable cardioverter defibrillator
      (ICD) may be beneficial when added to optimal drug treatment in patients with
      reduced left ventricular function who survive a myocardial infarction (MI).
      However, it is not known whether patients with increased risk of death after
      primary percutaneous coronary intervention (PCI) for ST-elevation MI also have
      benefit of prophylactic ICD therapy to reduce sudden cardiac death. METHODS AND
      STUDY DESIGN: The DAPA trial is designed to evaluate the efficacy and safety of
      ICD in high-risk patients after primary PCI for ST-elevation MI. In this
      randomized multicenter controlled study, a total of 700 patients will be
      included. Enrolment started in October 2004. Inclusion criteria are thrombolysis
      in myocardial infarction flow less than 3 after primary PCI or left ventricular
      ejection fraction lower than 30% as measured short after admission for the index
      MI. Patients will be randomized between 30 and 60 days after their MI. The
      primary end point will be total death during the follow-up period of at least 3
      years for each patient. CONCLUSIONS: This multicenter trial of patients at high
      risk of death after primary angioplasty for ST-elevation MI will evaluate
      prophylactic ICD therapy in addition to the current standard of care.

PMID- 16996828
TI  - Prevalence, predictors, and outcomes of patients with non-ST-segment elevation
      myocardial infarction and insignificant coronary artery disease: results from the
      Can Rapid risk stratification of Unstable angina patients Suppress ADverse
      outcomes with Early implementation of the ACC/AHA Guidelines (CRUSADE)
      initiative.
AB  - BACKGROUND: Unlike ST-segment elevation myocardial infarction, the degree of
      stenosis and physiology of ischemia varies in patients with non-ST-segment
      elevation myocardial infarction (NSTEMI). The prevalence, predictors, and
      outcomes of patients with NSTEMI who lack significant epicardial coronary artery
      disease (CAD) in routine clinical practice remain poorly characterized. We sought
      to determine the prevalence, predictors, and outcomes of patients with NSTEMI and
      insignificant CAD. METHODS: We analyzed 38301 patients with NSTEMI in the CRUSADE
      quality improvement initiative who underwent cardiac catheterization to determine
      the prevalence and factors associated with insignificant CAD (all coronary
      stenoses <50%) and inhospital outcomes for patients with and without CAD. A
      multivariable model was used to determine the factors associated with
      insignificant CAD. RESULTS: A total of 3306 (8.6%) of 38301 patients had
      insignificant CAD. The strongest multivariable predictors of insignificant CAD
      were female sex (odds ratio 2.8, 95% CI 2.6-3.1), younger age (odds ratio per 10
      year decrease 1.5, 95% CI 1.5-1.6), and lack of current/recent smoking (odds
      ratio 1.9, 95% CI 1.7-2.0). Inhospital rates of death were 0.65% for patients
      with insignificant CAD compared with 2.36% for patients with CAD (P < .0001).
      CONCLUSION: Insignificant CAD is present in 9% of patients with NSTEMI and is
      associated with a low incidence of adverse outcomes. The strongest predictors of
      insignificant CAD are female sex and younger age. These findings underscore the
      need for research to understand the pathophysiology of myocardial infarction in
      this population.

PMID- 16996829
TI  - The impact of emergency department structure and care processes in delivering
      care for non-ST-segment elevation acute coronary syndromes.
AB  - BACKGROUND: We sought to assess the influence of emergency department (ED)
      structure and care processes on adherence to practice guidelines for the
      treatment of patients with non-ST-segment elevation acute coronary syndromes.
      METHODS: We surveyed emergency physicians and nurses from 316 hospitals
      participating in the CRUSADE Quality Improvement Initiative and used
      multivariable modeling to correlate ED-specific characteristics with guidelines
      adherence. RESULTS: Factors that were significantly associated with improved
      guidelines adherence included collaboration between emergency physicians and
      hospital administration, northeast region, adequate nursing support, use of locum
      tenens physicians, an independent ED (not a division of another clinical
      department), and use of a care algorithm for acute coronary syndromes.
      CONCLUSIONS: Quality improvement strategies that have the full support of
      hospital administration, focus on increasing collaboration between emergency
      physicians and other health care providers, and specified protocol-driven
      management algorithm may be the most successful methods for improving the care
      and outcomes of patients with non-ST-segment elevation acute coronary syndromes.

PMID- 16996830
TI  - Rationale for establishing regional ST-elevation myocardial infarction receiving
      center (SRC) networks.
AB  - Recent developments have provided a unique opportunity for the organization of
      regional ST-elevation myocardial infarction (STEMI) receiving center (SRC)
      networks. Because cumulative evidence has demonstrated that rapid primary
      percutaneous coronary intervention (PCI) is the most effective reperfusion
      strategy for acute STEMI, the development of integrated SRC networks could extend
      the benefits of primary PCI to a much larger segment of the US population.
      Factors that favor the development of regional SRC networks include results from
      recently published clinical trials, insight into contemporary STEMI treatment
      patterns from observational registries, experience with the nation's current
      trauma system, and technological advances. In addition, the 2004 American College
      of Cardiology/American Heart Association STEMI guidelines have specified that
      optimal "first medical contact-to-balloon" times should be <90 minutes, so a
      clear benchmark for timely reperfusion has been established. Achievement of this
      benchmark will require improvements in the current process of care as well as
      increased multidisciplinary cooperation between emergency medical services,
      emergency medicine physicians, and cardiologists. Two types of regional SRC
      networks have already begun to evolve in role-model cities, including prehospital
      cardiac triage and interhospital transfer. Regional coordination of SRC networks
      is needed to ensure quality monitoring and to delineate the ideal reperfusion
      strategy for a given community based on available resources and expertise.

PMID- 16996831
TI  - Early initiation of eptifibatide in the emergency department before primary
      percutaneous coronary intervention for ST-segment elevation myocardial
      infarction: results of the Time to Integrilin Therapy in Acute Myocardial
      Infarction (TITAN)-TIMI 34 trial.
AB  - BACKGROUND: Early restoration of epicardial flow before primary percutaneous
      coronary intervention (PCI) for ST-segment elevation myocardial infarction
      (STEMI) has been associated with improved clinical outcomes. METHODS: We
      hypothesized that early administration of the glycoprotein IIb/IIIa inhibitor
      eptifibatide in the emergency department (ED) would yield superior epicardial
      flow and myocardial perfusion before primary PCI compared with initiating
      eptifibatide after diagnostic angiography in the cardiac catheterization
      laboratory (CCL). Three hundred forty-three patients with STEMI were randomized
      to either early ED eptifibatide (n = 180) or CCL eptifibatide (n = 163). RESULTS:
      The primary end point (pre-PCI corrected TIMI frame count) was significantly
      lower (faster flow) with early eptifibatide (77.5 +/- 32.2 vs 84.3 +/- 30.7, P =
      .049). The incidence of normal pre-PCI TIMI myocardial perfusion was increased
      among patients treated in the ED versus CCL (24% vs 14%, P = .026). There was no
      excess of TIMI major or minor bleeding among patients treated in the ED versus
      CCL (6.9% [12/174] vs 7.8% [11/142], P = NS). CONCLUSION: A strategy of early
      initiation of eptifibatide in the ED before primary PCI for STEMI yields superior
      pre-PCI TIMI frame counts, reflecting epicardial flow, and superior TIMI
      myocardial perfusion compared with a strategy of initiating eptifibatide in the
      CCL without an increase in bleeding risk.

PMID- 16996832
TI  - Underuse of evidence-based treatment partly explains the worse clinical outcome
      in diabetic patients with acute coronary syndromes.
AB  - BACKGROUND: Diabetes-related differences in treatment and clinical outcome of
      patients across the entire spectrum of acute coronary syndromes (ACSs) have
      potential clinical implications but have not been well studied. METHODS: The
      multicenter, prospective, Canadian ACS Registry enrolled 4578 patients
      hospitalized for ACS between 1999 and 2001 across 9 provinces in Canada. We
      compared baseline characteristics, in-hospital and post-discharge treatments, and
      clinical outcome of diabetic and non-diabetic patients. The impact of diabetes on
      use of thrombolytic therapy and coronary revascularization; and the independent
      association between diabetes, treatments, and diabetes-treatment interactions on
      outcome were examined. RESULTS: Diabetic patients with ACS had more
      cardiovascular risk factors and higher-risk clinical presentation. They
      paradoxically received less evidence-based medications in-hospital, at discharge,
      and at 1-year. Although diabetes independently predicted higher 1-year mortality
      (OR 1.47, 95% CI 1.15-1.87; P = .002) after adjustment for validated
      prognosticators, it was also an independent predictor of not receiving
      thrombolytic therapy (OR 0.72, 95% CI 0.54-0.95; P = .021) and coronary
      revascularization (OR 0.69, 95% CI 0.59-0.82; P < .001). These underused
      therapies were all independently associated with reduced 1-year mortality, with
      no significant diabetes-related treatment-outcome heterogeneity. Importantly,
      diabetes remained an independent adverse prognosticator even after further
      adjustment for these differences in treatment. CONCLUSIONS: Evidence-based
      therapies are underused in the contemporary management of diabetic patients with
      ACS, which partly explains their worse outcome. Diabetes should be considered a
      high-risk feature in ACS risk stratification that encourages more intensive
      treatments. Continued efforts to promote adherence to existing proven therapies
      and to develop novel treatment strategies targeting diabetes-specific
      cardiovascular pathophysiology are imperative to improve their adverse prognosis.

PMID- 16996833
TI  - Age, outcomes, and treatment effects of fibrinolytic and antithrombotic
      combinations: findings from Assessment of the Safety and Efficacy of a New
      Thrombolytic (ASSENT)-3 and ASSENT-3 PLUS.
AB  - BACKGROUND: Elderly patients with acute myocardial infarction are at particularly
      high risk for death and bleeding complications. The efficacy and safety of
      antithrombotic strategies in these patients remain unclear. METHODS: To provide
      more insight into the risk and benefit of antithrombotic strategies in the
      elderly, we examined patients from the ASSENT-3 and ASSENT-3 PLUS trials with
      STEMI who were treated with tenecteplase (TNK) and unfractionated heparin (UFH)
      or enoxaparin, or half-dose TNK with abciximab and reduced-dose UFH. RESULTS:
      Older patients had a higher risk profile, and lower use of concomitant therapies
      and revascularization procedures. We found an interaction between age and
      treatment effect for the efficacy end point (P = .0007) and the efficacy plus
      safety end point (P < .0001). Younger patients (<65 years) had a lower risk of
      the composite efficacy plus safety end point with enoxaparin (relative risk [RR]
      0.84, 95% CI 0.74-0.94) or abciximab (RR 0.79, 95% CI 0.69-0.90) compared with
      UFH. In patients >65 years of age, the benefit of enoxaparin appeared to be
      offset by an increased risk of bleeding complications. The risk of the efficacy
      plus safety end point tended to be higher in elderly patients receiving abciximab
      and half-dose TNK (RR 1.18, 95% CI 0.91-1.51 for 76-85 years of age and RR 1.48,
      95% CI 0.88-2.49 for >85 years of age). CONCLUSIONS: Although TNK with either
      enoxaparin or abciximab appeared to be more effective than with standard UHF in
      younger patients, these combinations tended to be less effective and even may be
      unsafe in the elderly. Development of new combination strategies and dosing
      schemes of fibrinolytics and antithrombotics with improved efficacy and safety in
      the elderly remains a high priority.

PMID- 16996834
TI  - Sustained effect of autologous bone marrow mononuclear cell injection in patients
      with refractory angina pectoris and chronic myocardial ischemia: twelve-month
      follow-up results.
AB  - BACKGROUND: Cell therapy has recently been introduced to treat patients with
      refractory angina. Because most studies have only included short-term follow-up,
      the effects of cell therapy over a longer period are unknown. METHODS: In 25
      patients (mean age 64 +/- 10 years, 21 men) with refractory angina, a total of 84
      +/- 29 x 10(6) bone marrow-derived mononuclear cells was injected
      intramyocardially in regions with ischemia on technetium-99m tetrofosmin single
      photon emission computed tomography. Anginal symptoms and quality of life were
      evaluated at baseline and at 3, 6, and 12 months. Gated single-photon emission
      computed tomography was performed at baseline and at 3 and 12 months to assess
      myocardial perfusion and left ventricular function. RESULTS: Bone marrow cell
      injection was performed without any complication. At 7 months, one patient died
      of intracranial hemorrhage. Canadian Cardiovascular Society class improved from
      3.4 +/- 0.5 to 2.3 +/- 0.6 at 3 months, 2.4 +/- 0.6 at 6 months, and 2.7 +/- 0.8
      at 12 months (P < .01). Quality of life improved from 53% +/- 10% to 71% +/- 11%
      at 3 months, 72% +/- 14% at 6 months, and 68% +/- 14% at 12 months (P < .01). The
      number of segments with ischemia per patient decreased from 4.7 +/- 3.3 to 2.1 +/
      2.6 at 3 months and 1.6 +/- 2.5 at 12 months (P < .01). Left ventricular
      ejection fraction increased from 47% +/- 13% to 53% +/- 17% at 3 months and 51%
      +/- 17% at 12 months (P < .01). Regional wall motion improved from 5.9 +/- 1.7 to
      6.6 +/- 2.2 mm at 3 months and 6.4 +/- 2.0 mm at 12 months (P = .01).
      CONCLUSIONS: Autologous bone marrow cell injection in patients with ischemia is
      safe and results in a sustained beneficial effect on anginal symptoms, myocardial
      perfusion, and left ventricular function.

PMID- 16996835
TI  - Home defibrillation: a feasibility study in myocardial infarction survivors at
      intermediate risk of sudden death.
AB  - BACKGROUND: Out-of-hospital cardiac arrest occurs at home in 65-80% of cases and
      is often witnessed. We designed a study to explore the feasibility of a home
      defibrillation program (a) evaluating the retention of cardiopulmonary
      resuscitation and automated external defibrillators (AED) use skills (BLSD) (b)
      assessing the impact on anxiety, depression, and quality of life and (c)
      recording the critical issues emerging from program implementation. METHODS:
      Thirty-three post-myocardial infarction patients and their 56 relatives received
      BLSD training and an AED. Assessment of BLSD skills, levels of anxiety, and
      depression and quality of life were scheduled every 3 months for 1 year or until
      a common stopping date. RESULTS: Overall BLSD score was 26 +/- 3 at baseline vs.
      22 +/- 5 at 3 months (P < .0001), 21 +/- 6 at 6 months (P < .0001), 22 +/- 4 at 9
      months (P < .0001) and 23 +/- 5 at 12 months (P = .001). Conversely, the BLSD
      component AED use" remained stable throughout the study. Quality of life,
      anxiety, and depression scores remained constant. Compliance to BLSD retraining
      sessions and AEDs checks decreased over time and was influenced by a concomitant
      clinical appointment. CONCLUSIONS: BLSD performance of families of post
      myocardial infarction patients decreases over time, even though the ability to
      operate AEDs appears to be the least affected component. Compliance with
      retraining sessions and AED checks declines over time and is improved if they are
      combined with clinical appointments. The implementation of a home defibrillation
      program does not affect anxiety, depression, or the quality of life.

PMID- 16996836
TI  - Interhospital transfer for early revascularization in patients with ST-elevation
      myocardial infarction complicated by cardiogenic shock--a report from the SHould
      we revascularize Occluded Coronaries for cardiogenic shocK? (SHOCK) trial and
      registry.
AB  - BACKGROUND: Early revascularization (ERV) in patients with ST-elevation
      myocardial infarction (STEMI) and cardiogenic shock (CS) reduces mortality rates.
      Patients admitted to hospitals without revascularization capability have high
      mortality rates and are not often transferred for ERV. METHODS: Transfer and
      direct-admit patients with STEMI from the SHOCK Trial and Registry with left
      ventricular failure (N = 969) were analyzed to determine benefit of ERV in
      transfer patients. RESULTS: Transfer patients (46%) were younger and less likely
      to have prior hypertension, myocardial infarction, and heart failure. They
      received more aggressive treatment, were revascularized later after CS (median
      7.3 vs 3.9 hours, P = .0002), and had similar adjusted inhospital mortality
      compared with direct-admit patients (55% vs 56%). Inhospital mortality was lower
      in ERV than no/late revascularization (41% vs 53%, P = .017 for transfer
      patients; 55% vs 71%, P = .0003 for direct-admit patients). Multiple logistic
      regression showed that inhospital mortality was associated with age (odds ratio
      [OR] 1.50 per decade increase, 95% CI 1.31-1.73, P < .0001), mean arterial
      pressure (OR 0.98 per 1 mm Hg increase, 95% CI 0.97-0.99, P < .0001),
      fibrinolysis before CS (OR 0.65, 95% CI 0.52-0.96, P = .040), and ERV (OR 0.70,
      95% CI 0.52-0.96, P = .028), but not transfer admission (OR 1.23, 95% CI 0.86
      1.74, P = .26). CONCLUSIONS: Despite longer time to treatment, transfer patients
      are a selected population with similar adjusted inhospital mortality and ERV
      benefit as direct-admit patients. Selected patients with STEMI and CS admitted to
      hospitals without revascularization capability should be transferred to centers
      with revascularization capability for immediate angiography.

PMID- 16996837
TI  - Uvulopalatopharyngoplasty decreases levels of C-reactive protein in patients with
      obstructive sleep apnea syndrome.
AB  - BACKGROUND: C-reactive protein is a crucial risk factor for cardiovascular
      diseases. Previous studies demonstrated that in patients with obstructive sleep
      apnea syndrome (OSAS), levels of this protein elevate dependently on the degree
      of upper airway obstruction. However, it has not been determined whether the
      surgery for OSAS reduces the levels of C-reactive protein by restoring the airway
      opening. Therefore, we evaluated the effect of uvulopalatopharyngoplasty (UPPP)
      on levels of serum C-reactive protein in patients with this syndrome. METHODS:
      Fifteen adult patients with mild to severe OSAS were enrolled in this study.
      Levels of serum C-reactive protein and sleep parameters including apnea-hypopnea
      index a month before and 3 months after UPPP were evaluated using peripheral
      venous blood and polysomnography, respectively. RESULTS:
      Uvulopalatopharyngoplasty significantly restored sleep parameters, accompanying
      with decreased levels of C-reactive protein (from 0.21 +/- 0.17 to 0.10 +/- 0.16
      mg/dL, P < .05). CONCLUSIONS: In patients with OSAS, UPPP appears to decrease
      levels of serum C-reactive protein. Surgical therapy may reduce inflammatory
      response in these patients.

PMID- 16996838
TI  - Weight loss improves heart rate recovery in overweight and obese men with
      features of the metabolic syndrome.
AB  - BACKGROUND: Heart rate recovery (HRR) is an independent risk factor for
      cardiovascular disease (CVD) and mortality, but whether it is modifiable and can
      improve with weight loss is unclear. We sought to determine the effects of weight
      loss on HRR and its association with traditional CVD risk markers. METHODS: Heart
      rate recovery (defined as the decrease in heart rate from peak heart rate to that
      measured 1 minute after a standardized graded treadmill test) and a range of
      established cardiovascular risk factors were measured in 42 overweight and obese
      men (body mass index 33.8 +/- 0.6 kg/m2, mean age 46.5 +/- 1.3 years) who had no
      symptoms of CVD but had components of the metabolic syndrome before and after 12
      weeks of weight loss. RESULTS: There was a 9% weight reduction (P < .001), with
      losses of 6.3 +/- 0.6 kg of fat mass (P < .001) and 3.1 +/- 0.6 kg of non-bone
      fat-free mass (P < .001). There were significant reductions in waist
      circumference, blood pressure, plasma triglycerides, total cholesterol, low
      density lipoprotein cholesterol, triglyceride/high-density lipoprotein ratio, C
      reactive protein, plasma insulin, glucose, and insulin resistance (P < .05).
      Although peak heart rate remained unchanged, HRR at 1 minute improved from 33.1
      +/- 1.4 to 36.9 +/- 1.3 beats/min (P < .001) after weight loss. There was no
      change in cardiorespiratory fitness (P = .30); neither was there any change in
      physical activity levels (P = .67). The improvement in HRR was significantly
      correlated with decreases in body weight, body mass index, waist circumference,
      plasma glucose, serum triglycerides, and triglyceride/high-density lipoprotein
      ratio; however, it was only independently associated with changes in weight and
      plasma glucose concentrations. CONCLUSION: In addition to improving a range of
      well-accepted cardiovascular and metabolic risk factors, weight loss also
      improves HRR after exercise, a less recognized risk factor.

PMID- 16996839
TI  - The impact of cardiovascular risk factors on subclinical left main coronary
      artery disease: an intravascular ultrasound study.
AB  - BACKGROUND: The impact of cardiovascular risk factors on subclinical but
      measurable left main coronary artery (LMCA) atherosclerosis is not well known.
      METHODS: We analyzed 150 consecutive patients with first-time coronary artery
      disease presentation undergoing intervention of a left anterior descending
      coronary artery or left circumflex lesion with motorized intravascular ultrasound
      transducer pullback that included a nonstenotic LMCA. Framingham, PROCAM, and
      European SCORE risk assessments were determined in 107 patients <65 years of age
      (because the Framingham, PROCAM, and European SCORE studies excluded patients >65
      years old). Intravascular ultrasound measurements were compared in patients with
      <10% vs 10% to 20% risk of events. RESULTS: Plaque volumes were greater in
      patients with higher risk scores: P = .007 in patients with 10% to 20% PROCAM
      risk, P = .063 in patients with 10% to 20% Framingham risk, and P = .059 in
      patients with 10% to 20% SCORE risk (P = .059). The mean arc of LMCA calcium (12
      degrees +/- 25 degrees overall) correlated with plaque volume (51 +/- 28 mm3, r =
      0.30, P = .0001) and with the number of coronary risk factors (P = .048) and
      ranged from 0.28 degrees +/- 0.74 degrees in patients with 0 to 1 risk factors to
      9.95 degrees +/- 21.55 degrees in patients with 2 to 4 risk factors to 19.38
      degrees +/- 32.51 degrees in patients with 5 to 7 risk factors. Regression
      analysis showed obesity and age were the most important factors contributing to
      LMCA calcium. CONCLUSION: Intravascular ultrasound measurable atherosclerosis in
      nonstenotic LMCA correlates with conventional primary coronary risk scores. Left
      main coronary artery calcium correlates both with LMCA plaque volume and risk
      factors. Thus, subclinical LMCA atherosclerosis may be a marker for events that
      are predicted by commonly used primary risk-assessment algorithms.

PMID- 16996840
TI  - Skin cholesterol adds to Framingham risk assessment.
AB  - INTRODUCTION: It has been demonstrated that skin tissue cholesterol (SkinTc) is
      associated with angiographic disease. Now, we further delineate the relative risk
      of multivessel disease (>50% stenosis in at least two vessels) in the conjoint
      presence of high SkinTc and high traditional risk burden. METHODS: Patients
      scheduled for angiography (N = 649) had SkinTc measured immediately prior to the
      procedure. Patients were classified according to the presence of high (>110)
      SkinTc and high (>10) Framingham global risk scores. Multivariable logistic
      regression models were used to estimate relative risk of multivessel disease for
      patients with isolated high skin tissue cholesterol, isolated high Framingham
      risk or conjoint high skin tissue cholesterol and high Framingham risk (each
      compared to neither factor elevated). RESULTS: The mean age was 63 +/- 12 years
      and 33% (n = 214) were women. Thirty seven percent (n = 237) had angiographically
      determined multivessel disease. Patients with isolated high SkinTc showed a
      relative risk of multivessel disease of 1.6 (95% CI = 1.0-2.4), while patients
      with isolated high Framingham risk had an odds ratio of 1.8 (CI = 1.0-3.4).
      However, when both scores were elevated, risk of multivessel disease was
      increased 4.3 times (CI = 2.6-7.2) compared to neither elevated. CONCLUSIONS: We
      see an independent, additive risk of concurrent multivessel disease when
      Framingham risk and skin cholesterol are both elevated. Skin tissue cholesterol
      may have value in further stratifying subjects with Framingham scores >10.

PMID- 16996841
TI  - Stimulating autoantibodies directed against the cardiac beta1-adrenergic receptor
      predict increased mortality in idiopathic cardiomyopathy.
AB  - BACKGROUND: The aim of this study was to estimate the independent and incremental
      prognostic value of the presence of stimulating autoantibodies directed against
      the human beta1-adrenergic receptor (anti-beta1-AR) in patients with chronic
      heart failure. METHODS: One hundred five antibody-typed chronic heart failure
      patients with dilated cardiomyopathy (DCM, n = 65) or ischemic cardiomyopathy
      (ICM, n = 40) were prospectively followed for 10.7 +/- 2.5 years. Information on
      all-cause and cardiovascular mortality was collected throughout the observation
      period. RESULTS: Stimulating anti-beta1-AR were prevalent in 26% (17/65) of
      patients with DCM and 13% (5/40) with ICM. All-cause mortality in antibody
      positive patients was 65% in those with DCM and 80% in those with ICM, and in
      antibody-negative patients 44% and 49%, respectively. In univariate and
      multivariable Cox regression analysis (P < .05), presence of stimulating anti
      beta1-AR was associated with increased all-cause and cardiovascular mortality
      risk in DCM but not in ICM. Information on antibody status improved the
      prognostic capacity in models containing already extensive information on
      clinical profile, Holter electrocardiography, and invasive hemodynamic
      measurements (area under the receiver operating characteristic curve, 0.91; 95%
      confidence interval, 0.85-0.97; P < .05 for increase in receiver operating
      characteristic area). CONCLUSION: The presence of stimulating anti-beta1-AR
      autoantibodies independently predicts increased all-cause and cardiovascular
      mortality risk in DCM conferring incremental prognostic value in addition to
      established risk predictors. Our data indicate a clinical relevance of
      stimulating anti-beta1-AR in DCM and encourage further research into antibody
      directed strategies as a therapeutic principle.

PMID- 16996842
TI  - Quantification of the risk and predictors of hyperkalemia in patients with left
      ventricular dysfunction: a retrospective analysis of the Studies of Left
      Ventricular Dysfunction (SOLVD) trials.
AB  - BACKGROUND: Limited data are available to predict the occurrence of hyperkalemia.
      Risk assessment is complicated by the lack of consistency of definition between
      trials. METHODS: We conducted a retrospective analysis of the SOLVD to evaluate
      the incidence of hyperkalemia and the value of several baseline characteristics
      as predictors of hyperkalemia in patients with left ventricular dysfunction.
      RESULTS: The incidence of hyperkalemia was 6.0% and 1.1% using a definition of >
      or = 5.5 and > or = 6.0 mmol/L, respectively. Independent predictors of
      hyperkalemia (> or = 5.5 mmol/L) were randomization to enalapril, baseline serum
      creatinine, serum potassium, New York Heart Association functional class III or
      IV, a history of diabetes, and atrial fibrillation (all P < .05). The use of loop
      diuretics was also associated with an increased risk of hyperkalemia but only in
      patients included in the SOLVD prevention trial. Similar results were obtained
      when renal function was evaluated using the estimated creatinine clearance.
      CONCLUSIONS: The definition of hyperkalemia is important when evaluating its
      incidence in clinical trials. Renal dysfunction, baseline serum potassium,
      diabetes, atrial fibrillation, New York Heart Association functional class, and
      treatment with an angiotensin-converting enzyme inhibitor are factors associated
      with the development of hyperkalemia in patients with left ventricular
      dysfunction. More specifically, our results suggests that before initiating drugs
      that can cause hyperkalemia in patients with heart failure, a strong
      consideration should be given to calculate creatinine clearance and that patients
      with a creatinine clearance < 60 mL/min should undergo a close monitoring of
      their serum potassium to prevent the development of hyperkalemia.

PMID- 16996843
TI  - Immunoadsorption in dilated cardiomyopathy: 6-month results from a randomized
      study.
AB  - BACKGROUND: Various randomized studies evidenced that immunoadsorption (IA)
      repeated at monthly intervals induced acute and prolonged hemodynamic benefit in
      patients with severe heart failure due to dilated cardiomyopathy. Some findings
      indicate that the use of only one course of IA therapy may also induce prolonged
      beneficial effects. METHODS: This randomized study included 22 patients suffering
      from severe heart failure (left ventricular ejection fraction [LVEF] <35%) due to
      dilated cardiomyopathy. The first group (11 patients) was treated with four IA
      courses at monthly intervals. The second group (11 patients) received one IA
      course only without repetition. In all patients of the 2 groups, each course was
      performed in one IA session on 5 consecutive days. At 3 and 6 months after the
      beginning of this study, left ventricular function and hemodynamics were
      reevaluated in both groups. RESULTS: Immunoadsorption treatment repeated at
      monthly intervals induced improvement in LVEF after 6 months, that is, from 28.1%
      +/- 1.5% to 37.0% +/- 1.6% (+/-SEM; P < .01 vs baseline). Patients treated in
      only one IA course experienced comparable improvement of LVEF after 6 months,
      that is, from 26.5% +/- 2.2% to 34.8% +/- 2.9% (P < .01 vs baseline). In the
      group with repeated IA courses, cardiac index increased from baseline 2.2 +/- 0.1
      to 2.8 +/- 0.2 L min(-1) m(-2) after 6 months (P < .01 vs baseline). In
      comparison, during the 6 months of this study in the group with one IA course,
      cardiac index increased from 2.1 +/- 0.1 to 2.7 +/- 0.2 L min(-1) m(-2). After 3
      and 6 months, there were no significant differences between the 2 groups with
      respect to LVEF and all measured hemodynamic parameters. CONCLUSIONS: One course
      of IA treatment may induce improvement of left ventricular function over a period
      of 6 months, with results comparable to those received by IA treatment repeated
      at monthly intervals.

PMID- 16996844
TI  - Adjunctive therapy with low-molecular-weight heparin in patients with chronic
      heart failure secondary to dilated cardiomyopathy: one-year follow-up results of
      the randomized trial.
AB  - BACKGROUND: Defective endothelial function has been shown in dilated
      cardiomyopathy. Therefore, improvement in endothelial function after low
      molecular-weight heparin (LMWH) therapy may be clinically beneficial.
      Consequently, the effect of adjunct enoxaparin, a LMWH, on standard treatment of
      dilated cardiomyopathy was investigated. METHODS: This was a randomized, standard
      treatment-controlled, 2-center pilot trial of 102 patients (52 receiving
      adjunctive therapy with enoxaparin at a dosage of 1.5 mg/kg daily for 3 months
      and 50 receiving standard therapy with angiotensin-converting enzyme inhibitors,
      beta-blockers, and diuretics alone) with stable chronic heart failure secondary
      to dilated cardiomyopathy (New York Heart Association [NYHA] class II and III;
      left ventricular [LV] ejection fraction, < or = 40%). All patients underwent
      coronary angiography and endomyocardial biopsy and were clinically stable for at
      least 6 months before enrollment. The combined primary end point included
      mortality, urgent heart transplantation, and readmission to hospital due to heart
      failure progression. The secondary end point was to determine the severity of
      heart failure (serum level of N-terminal brain natriuretic peptide), cardiac
      function (LV ejection fraction by radionuclide ventriculography), LV diameters by
      echocardiography, exercise capacity (changes in NYHA class, changes in peak
      oxygen consumption), and changes in quality of life (Minnesota Living with Heart
      Failure questionnaire). The clinical outcome was assessed after 6 and 12 months
      of therapy. RESULTS: Baseline characteristics were comparable in both groups.
      Five patients dropped out during 12 months of the study. Twelve patients achieved
      primary end point (8 in the control group and 4 in the LMWH group). The free
      survival rate was 94% for the LMWH group and 90% for the controls (not
      statistically significant). After the 12-month period, in the LMWH group, N
      terminal brain natriuretic peptide level and LV diameters decreased significantly
      (P < .001 and P = .006, respectively), whereas LV systolic function increased (P
      < .001). Changes in exercise capacity and subjective improvement did not
      differentiate the groups (nonsignificant). Adverse reactions to the enoxaparin
      therapy were minor and transient. CONCLUSIONS: In patients with chronic heart
      failure due to dilated cardiomyopathy, adjunct long-term enoxaparin therapy may
      offer additional clinical benefit without deleterious effects on major cardiac
      events.

PMID- 16996845
TI  - The effect of altering heart rate on ventricular function in patients with heart
      failure treated with beta-blockers.
AB  - BACKGROUND: Beta-blockers are effective for the treatment of heart failure, but
      their mechanism of action is unresolved. Heart rate reduction may be a central
      mechanism or a troublesome side effect. METHODS: A randomized, double-blind,
      parallel group study comparing chronic higher-rate (80 pulses per minute) with
      lower-rate (60 pulses per minute) pacing in pacemaker-dependent patients with
      symptomatic left ventricular (LV) systolic dysfunction, receiving beta-blockers.
      Gated radionuclide ventriculography (RNVG) was performed at baseline and after at
      least 9 months. The primary outcome was change in LV volumes, as a marker of
      beneficial reverse remodeling, from baseline to follow-up. RESULTS: Forty-nine
      patients were randomized. Mean age was 74 +/- 6 years and with LV ejection
      fraction of 26% +/- 9% at baseline. During 14 +/- 13 months of follow-up, 21
      patients (43%) died and 25 (51%) completed the study protocol: 12 in the higher
      rate and 13 in the lower-rate group. Mean LV end-diastolic (higher rate +20 +/-
      104 mL vs lower rate -65 +/- 92 mL, P = .03) and systolic (higher rate +29 +/- 83
      mL vs lower rate -60 +/- 74 mL, P = .006) volumes increased with higher-rate
      versus lower-rate pacing, whereas LV ejection fraction declined (higher rate 
      4.2% +/- 4.4% vs lower rate +2.2% +/- 5.4%, P = .002). CONCLUSION: Reversal of
      beta-blocker-induced bradycardia has deleterious effects on ventricular function,
      suggesting heart rate reduction is an important mediator of their effects. The
      prognosis of patients with pacemakers and heart failure is poor.

PMID- 16996846
TI  - Survival in octogenarians receiving implantable defibrillators.
AB  - BACKGROUND: Although clinical trials have expanded implantable defibrillator
      (ICD) indications, octogenarians have been poorly represented in these studies.
      Overall, survival in this subgroup is ill-defined. METHODS: Consecutive patients
      > or = 80 years of age at ICD implant between July 1995 and September 2003 were
      retrospectively analyzed. Kaplan-Meier survival analysis was performed, and
      mortality predictors were identified. Consecutive nonelderly patients aged 60 to
      70 years (60-70 group) who received ICDs over the same period were analyzed as a
      reference. Mortality predictors in the > or = 80 group were compared to the 60-to
      70 group. RESULTS: A total of 348 patients (age, > or = 80 years [n = 107]; age,
      60-70 years [n = 241]) were included. Mean follow-up time for the entire cohort
      was 3.3 +/- 2.2 years. Other than the estimated glomerular filtration rate (eGFR)
      (58 +/- 22 vs 66 +/- 22 mL/min) in the > or = 80 group versus the 60-to-70 group,
      no other differences in baseline characteristics were observed. Median survival
      was 4.2 years after implant in the > or = 80 group versus 7 years in the 60-to-70
      group (P < .01). Mortality predictors in the > or = 80 group included ejection
      fraction (EF) < or = 30% (hazard ratio [HR], 2.2; 95% confidence interval [CI],
      1.3-4.0) and eGFR < 60 mL/min (HR, 2.2; 95% CI, 1.3-3.7). In the 60-to-70 group,
      EF < or = 30% (HR, 2.7; 95% CI, 1.6-4.5), eGFR < 60 mL/min (HR, 3.4; 95% CI, 2.2
      5.3), diabetes (HR, 1.8; 95% CI, 1.9-2.9), and QRS width > 120 ms (HR, 2.1; 95%
      CI, 1.4-3.3) predicted mortality. QRS > 120 ms and diabetes were not predictors
      in octogenarians (HR, 1.1 and 1.5, respectively; 95% CI, 0.7-1.9 and 0.8-2.7,
      respectively). Analysis of octogenarians subgrouped by EF < or = 30% and eGFR <
      60 mL/min identified patients whose median survival was 6.1 years (neither
      predictor present; n = 28), 4.7 years (either predictor present; n = 46), and 19
      months (both predictors present; n = 33) (P < .01 between groups). Survival
      analysis in the > or = 80-year-old cohort grouped by eGFR quartile identified
      groups with median survival of 5.6, 4.7, 3.5 years, and 18 months, respectively,
      in the highest to the lowest eGFR quartile (> 75, 61-75, 41-60, and < 41 mL/min).
      CONCLUSIONS: Median survival in octogenarian ICD recipients is greater than 4
      years. In addition to baseline EF, eGFR is a strong predictor of mortality in
      elderly ICD candidates. These easily identifiable clinical variables may assist
      clinical decision making and help to provide appropriate post-ICD implant
      survival expectations in this elderly patient group.

PMID- 16996847
TI  - Potential applicability and utilization of left atrial appendage occlusion
      devices in patients with atrial fibrillation.
AB  - BACKGROUND: The WATCHMAN left atrial appendage occluder device (Atritech, Inc,
      Minneapolis, MN) is currently being tested in a Food and Drug Administration
      approved clinical trial, the PROTECT AF trial, for patients who are diagnosed
      with paroxysmal, persistent, or permanent nonvalvular atrial fibrillation.
      However, rigorous screening and the study design have resulted in the exclusion
      of a large number of patients. Hence, the purpose of this study was to assess the
      potential utility of this device among those who were eligible but excluded for
      trial criteria and the reasons for exclusion. METHODS: Screening logs from the
      respective sites participating in the PROTECT AF trial were collected and
      analyzed for potential utilization outside of a research trial. Only 31 patients
      were enrolled into the research trail from the screening of 1798 total patients.
      RESULTS: Information from the excluded patients was examined and it was
      determined that 79% of these patients would be eligible for the device outside
      the research trial. Twenty-one percent of patients were not able to receive the
      device because of long-term warfarin need, contraindications to warfarin,
      unsuitable anatomy as determined by echocardiography, or the inability to take
      short-term aspirin and clopidogrel for protocol requirements. CONCLUSIONS: Should
      a device like the WATCHMAN left atrial appendage occluder be approved,
      approximately 79% of all patients with atrial fibrillation would be eligible for
      device placement.

PMID- 16996848
TI  - A history of heart failure predicts arrhythmia treatment efficacy: data from the
      Antiarrythmics versus Implantable Defibrillators (AVID) study.
AB  - BACKGROUND: In survivors of life-threatening ventricular tachycardia (VT), a
      history of CHF (HxCHF) before the VT episode may provide different prognostic
      information than their measured left ventricular ejection fraction (LVEF).
      METHODS: We evaluated outcomes from patients in the AVID study. Patients were
      included in the study if they presented with ventricular fibrillation, VT with
      syncope or VT with hemodynamic compromise, and LVEF < or = 40%. Treatment options
      included implantable cardioverter defibrillator (ICD) or antiarrhythmic drugs
      (AAD), usually amiodarone. RESULTS: As expected, a HxCHF is associated with an
      increased and high risk of arrhythmic and nonarrhythmic death. However, an
      interaction was observed between arrhythmia treatment (ICD or AAD) and HxCHF
      status: the survival advantage with an ICD, as compared with AAD therapy, is
      largely restricted to HxCHF patients. CONCLUSIONS: The ICD is no better than AAD
      therapy in preventing arrhythmic death in patients with no HxCHF. In this data
      set, a HxCHF is somewhat more accurate in predicting prognosis and the response
      to therapy than a reduced LVEF.

PMID- 16996849
TI  - ST-segment abnormalities and premature complexes are predictors of new-onset
      atrial fibrillation: the Niigata preventive medicine study.
AB  - BACKGROUND: Left ventricular hypertrophy is a known risk factor for atrial
      fibrillation (AF). However, it is not well understood whether other
      electrocardiogram abnormalities are associated with development of AF. METHODS:
      This was a community-based cohort study based upon a database of annual health
      examinations. We included 63,386 subjects aged > or = 50 years, without baseline
      AF (including atrial flutter), structural heart disease, or heart failure, who
      completed the annual examination during a 10-year follow-up period (1991-2002).
      The electrocardiographic risk factors for AF were studied in the subjects.
      RESULTS: Atrial fibrillation developed in 873 subjects. Age, male sex, body mass
      index, hypertension, systolic and diastolic blood pressure, and diabetes were
      significant risk factors for the development of AF. In multivariable logistic
      regression analysis adjusted for these risk factors, electrocardiographic left
      ventricular hypertrophy (odds ratio [OR], 1.43), ST-segment abnormality without
      left ventricular hypertrophy (OR, 1.89), and the presence of premature complexes
      during a 10-second recording (OR, 2.89) were significantly associated with AF,
      whereas either right (OR, 0.84) or left bundle branch block (OR, 0.96) was
      unrelated. The risk for AF increased progressively with the severity of both ST
      segment change and premature complexes. CONCLUSIONS: ST-segment abnormality and
      comparably high-frequency premature complexes were each associated with increased
      risk for the development of AF. These electrocardiographic findings may be useful
      to stratify high-risk subjects for new-onset AF.

PMID- 16996850
TI  - The impact of the AMPD1 gene polymorphism on exercise capacity, other prognostic
      parameters, and survival in patients with stable congestive heart failure: a
      study in 686 consecutive patients.
AB  - BACKGROUND: Previous studies have demonstrated that the adenosine monophosphate
      deaminase 1 (AMPD1) C34T polymorphism may be associated with survival in cardiac
      populations with a protective effect of the T allele. However, these studies
      included limited number of patients with few cardiovascular events. METHODS: We
      prospectively analyzed the impact of the C34T polymorphism of the AMPD1 gene in
      686 unrelated white patients with stable congestive heart failure related to left
      ventricular systolic dysfunction. Patients underwent echocardiography,
      radionuclide angiography, and a cardiopulmonary exercise test. Blood samples were
      drawn for standard and hormonal determinations and for genetic analysis. RESULTS:
      There were 517 (75%) CC homozygotes, 155 (23%) CT heterozygotes, and 14 (2%) TT
      mutated homozygotes. We did not demonstrate any impact of this polymorphism on
      clinical, biologic, echocardiographic, radionuclide, and exercise parameters in
      the whole population and in ischemic and nonischemic subgroups of patients.
      During a median follow-up period of 3 years, there were 145 cardiac-related
      deaths and 6 urgent transplantations. There was no impact of this polymorphism on
      survival. CONCLUSIONS: In our population, we did not demonstrate any effect of
      the C34T polymorphism of the AMPD1 gene on major congestive heart failure
      parameters and on survival.

PMID- 16996851
TI  - Lack of sensitivity of the electrocardiogram for detection of old myocardial
      infarction: a cardiac magnetic resonance imaging study.
AB  - BACKGROUND: The presence of Q waves in the electrocardiogram (ECG) has been used
      as a marker of prior myocardial infarction (MI). Its accuracy, however, is
      uncertain. The purpose of this study is to determine the accuracy of an ECG to
      detect prior MI compared with a novel criterion standard. METHODS: This study
      conducted retrospective inclusion with de novo analysis of ECG and cardiac
      magnetic resonance (CMR) by independent blinded readers in a single-institution
      setting. The population consisted of a consecutive sample of 146 patients
      referred for CMR for evaluation of myocardial viability and necrosis. Q/QS waves
      on ECG were defined as per Minnesota Code criteria. Myocardial scar was
      quantified and localized by CMR delayed contrast hyperenhancement and assumed as
      criterion standard. Sensitivity, specificity, and predictive values of ECG were
      calculated for different scar sizes (>1%, >15%, and >30% of the myocardium) and
      location (global, anterior, inferior, and lateral walls). RESULTS: Sensitivity
      was 48.4%; specificity, 83.5; positive predictive accuracy, 72.0%; and negative
      predictive accuracy, 64.2%. Sensitivity improved when only large infarcts were
      considered (64.2%), but specificity decreased to 72.7%. Sensitivity for detecting
      isolated anterior or inferior wall scars was similar, but isolated lateral wall
      scar was rarely identified (14.3%). When all 3 walls were involved, sensitivity
      was still low at 57.9%. CONCLUSIONS: The lack of sensitivity and the resulting
      low negative predictive value of Q/QS criteria seriously limit its accuracy as a
      marker of prior MI.

PMID- 16996852
TI  - The prognostic value of the mitral diastolic filling velocity ratio for all-cause
      mortality and cardiovascular morbidity in African Americans: the Atherosclerotic
      Risks in Communities (ARIC) study.
AB  - BACKGROUND: Although recent data suggest that the mitral diastolic early-to-late
      (E/A) ratio may be prognostic in selected population-based cohorts, its
      predictive value for morbidity and mortality in African Americans has not yet
      been well studied. METHODS: The study population consisted of African American
      participants from the Jackson cohort of the Atherosclerotic Risks in Community
      Study. Three subgroups of E/A ratios were defined: E/A <0.7, E/A 0.7-1.5, and E/A
      >1.5, using the middle group as reference. Cox proportional hazard models were
      used to assess the association between the E/A ratio and both all-cause mortality
      and incident cardiovascular disease (CVD). The mean follow-up period was 6.8 +/-
      1.3 years. RESULTS: Of the 2211 participants in the study population (mean age 62
      years, 65.1% women), 8.2% had an E/A ratio <0.7, 84.7% had an E/A 0.7-1.5, and
      7.1% had an E/A >1.5. An E/A >1.5 was independently associated with all-cause
      mortality (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.20-4.03) in the
      multivariable model. An E/A <0.7 was associated with higher all-cause mortality
      (HR 1.79, 95% CI 1.17-2.73) and incident CVD (HR 1.91, 95% CI 1.29-2.83) compared
      with a normal E/A in the age and sex adjusted model but was not independently
      predictive in the multivariable model (P > .05). CONCLUSIONS: In a population
      based cohort of middle-aged African Americans, an E/A >1.5 independently predicts
      all-cause mortality. An E/A >1.5 and an E/A <0.7 were both associated with
      incident CVD when adjusted for age and sex alone but were not independently
      predictive in the multivariable analysis.

PMID- 16996853
TI  - Measurement of the thickness of the fibrous cap by optical coherence tomography.
AB  - BACKGROUND: Identification of the fibrous cap is important because its thickness
      is a major determinant of plaque vulnerability in lipid-rich plaque. Thus, a high
      resolution imaging technique may be a promising method for the identification of
      the fibrous cap within lipid-rich plaque. The purpose of this study was to
      investigate the feasibility of using optical coherence tomography (OCT) to
      measure the thickness of the fibrous cap within lipid-rich plaque. METHODS AND
      RESULTS: We examined 35 lipid-rich plaques from 102 coronary arterial segments of
      38 human cadavers (22 men and 16 women; mean ages, 74 +/- 7 years). Optical
      coherence tomography and corresponding histological images were digitized for
      measurement of the thickness of fibrous cap, and the results between OCT and
      histological examination were compared. There was good correlation of the
      thickness of the fibrous cap between OCT and histological examination (y = 0.97x
      + 28.49; r = 0.90; P < .001). A Bland-Altman test showed good agreement of the
      thickness of the fibrous cap between OCT and histological examination (mean
      difference, -24 +/- 44 microm). CONCLUSIONS: Optical coherence tomography
      provides an accurate representation of the thickness of the fibrous cap and may
      prove useful in assessing plaque vulnerability in lipid-rich plaque.

PMID- 16996854
TI  - Association between thrombolysis in myocardial infarction myocardial perfusion
      grade, biomarkers, and clinical outcomes among patients with moderate- to high
      risk acute coronary syndromes: observations from the randomized trial to evaluate
      the relative PROTECTion against post-PCI microvascular dysfunction and post-PCI
      ischemia among antiplatelet and antithrombotic agents-Thrombolysis In Myocardial
      Infarction 30 (PROTECT-TIMI 30).
AB  - BACKGROUND: A variety of imaging modalities have implicated impaired myocardial
      perfusion in the pathogenesis of acute coronary syndromes (ACSs). METHODS: We
      hypothesized that an abnormal TIMI myocardial perfusion grade (TMPG 0/1/2) and an
      impaired coronary flow reserve (CFR) as assessed angiographically using the TIMI
      frame count would be associated with biomarker release, ischemia on Holter
      monitoring, and adverse clinical outcomes in the PROTECT-TIMI 30 trial of
      patients with non-ST-elevation ACS undergoing percutaneous coronary intervention
      (PCI). RESULTS: The pre-PCI TMPG was correlated with the baseline as well as peak
      levels of troponin I (P < .001) and creatine kinase-MB (P < .001) and the post
      PCI rise in troponin I (P = .03). The incidence of an ischemic event on Holter by
      48 hours was more common among patients with an abnormal post-PCI TMPG (12.5% vs
      7.0%, P = .013), and the mean normalized duration of ischemia by 24 hours after
      PCI on Holter monitoring trended longer among patients with an abnormal post-PCI
      TMPG (8.9 vs 3.2 minutes, P = .068). In multivariable analyses, an abnormal post
      PCI TMPG was the strongest correlate of death, myocardial infarction, or an
      ischemic event by 48 hours after randomization. In contrast, the post-PCI CFR as
      assessed angiographically using the TIMI frame count was not associated with the
      baseline, peak, or absolute rise of any biomarker, Holter findings, or clinical
      events. CONCLUSIONS: An abnormal TMPG, but not an angiographic CFR, is associated
      with biomarker status, the occurrence and duration of Holter ischemia, and
      adverse clinical outcomes among patients with moderate- to high-risk non-ST
      elevation ACS undergoing PCI.

PMID- 16996855
TI  - A double-blind, randomized, placebo-controlled multicenter clinical trial to
      evaluate the effects of the angiotensin II receptor blocker candesartan cilexetil
      on intimal hyperplasia after coronary stent implantation.
AB  - BACKGROUND: Preclinical data suggest beneficial effects of angiotensin II
      receptor blockers (ARBs) on neointima formation after vascular injury.
      Preliminary clinical data, however, revealed conflicting results. The AACHEN
      trial was a double-blind, randomized, placebo-controlled clinical multicenter
      trial to evaluate the effects of candesartan cilexetil on intimal hyperplasia
      after coronary stent implantation. METHODS: A total of 120 patients (61 +/- 9
      years, 83% male) were randomized to receive either 32 mg candesartan cilexetil
      (active) or placebo starting 7 to 14 days before elective coronary stent
      implantation. A follow-up angiography including intravascular ultrasound
      assessment of the target lesion was performed 24 +/- 2 weeks after stent
      implantation. The primary end point was defined as the difference in neointimal
      area between groups as assessed by intravascular ultrasound. Secondary end points
      included differences in angiographic parameters (ie, restenosis rate) and
      incidence of major cardiac events. RESULTS: The mean stent length measured 15.0
      +/- 4.9 mm in the active and 14.6 +/- 5.7 mm in the placebo group (P = .81).
      There was no significant difference in neointimal area between groups (2.1 +/-
      1.0 vs 2.1 +/- 1.5 mm2, P = 1.00), nor were there differences in angiographic end
      point parameters. Major cardiac event rates were not significantly different
      between treatment groups (8% vs 11%, P = .75). CONCLUSIONS: High-dose candesartan
      cilexetil therapy in patients with symptomatic coronary artery disease undergoing
      coronary stent implantation does not reduce clinical event rates, restenosis
      rates, or neointimal proliferation after elective stent implantation.

PMID- 16996856
TI  - Predictors of long-term outcome after crush stenting of coronary bifurcation
      lesions: importance of the bifurcation angle.
AB  - OBJECTIVES: We hypothesized that the bifurcation angle (BA) may affect the
      outcome of crush stenting (CS) of bifurcation lesions and thus set out to
      determine the effect of the BA on outcome of patients undergoing coronary
      bifurcation CS. METHODS: Of 538 bifurcation PCI cases performed between November
      2003 and March 2005, 133 were performed using CS (n = 56), balloon CS (n = 71),
      or reverse CS (n = 6). Patients were divided into low-angle and high-angle groups
      using the median BA as the cut point. RESULTS: The median BA was 50 degrees. High
      angle patients were more likely to be women (33% vs 15%, P = .02), with a prior
      percutaneous coronary intervention (26% vs 12%. P = .05) and coronary artery
      bypass grafting (15% vs 5%, P = .05). Procedural success was 98.5% in the low
      angle and 95.4% in the high-angle group (P = nonsignificant). Two high-angle
      patients had acute stent thrombosis, and 1 died in hospital. Four additional high
      angle patients (6.1%) and 1 low-angle patient (1.5%) died (P = nonsignificant)
      during follow-up. Major adverse cardiac events (MACE) occurred more frequently in
      the high-angle group (22.7% vs 6.2%, P = .007). Bifurcation angle > or = 50
      degrees (P = .004), no final kissing balloon inflation (P = .012), and creatinine
      clearance < 40 mL/min (P = .031) independently predicted MACE. CONCLUSIONS:
      Bifurcation angle > or = 50 degrees is an independent predictor of MACE after
      bifurcation CS, in addition to no final kissing balloon inflation and severe
      renal dysfunction. A high BA confers a setting of increased turbulent flow that
      is further exacerbated by suboptimal treatment of the crushed side-branch stent.
      Further study to improve outcome in this subset of patients is warranted.

PMID- 16996857
TI  - Reduced 6-month resource use and costs associated with cilostazol in patients
      after successful coronary stent implantation: results from the Cilostazol for
      RESTenosis (CREST) trial.
AB  - BACKGROUND: The CREST trial demonstrated that after successful coronary stent
      implantation, the 6-month rate of target vessel revascularization (TVR) was
      similar (15.4% vs 16%, P = .90) for the 2 treatment groups, but restenosis rate
      was lower (22.0% vs 34.5%, P = .002) in cilostazol-treated patients. We sought to
      evaluate resource use, cost, and cost-effectiveness of cilostazol in CREST.
      METHODS: A total of 705 patients were randomized to cilostazol 100 mg twice daily
      (n = 354) versus placebo (n = 351) for 6 months. Resources included
      rehospitalizations, medications, and outpatient services. Costs were determined
      from the Medicare fee schedule. Cilostazol was priced at 1.64 dollars a day. Base
      case cost and cost-effectiveness analysis was performed for the entire population
      using TVR as a measure of effectiveness. Sensitivity analysis was conducted among
      526 patients because restenosis data were available only for this patient
      population. A bootstrap resample approach (5000 samples) was used to obtain
      confidence intervals for cost differences. RESULTS: For the entire population,
      costs of rehospitalizations, concomitant medications, outpatient tests, and
      physician or emergency department visits were lower during follow-up for
      cilostazol-treated patients. Overall, total 6-month follow-up costs remained 447
      dollars lower for cilostazol (4178 dollars vs 4625 dollars), although this
      difference did not reach significance (95% CI -1458 dollars to 515 dollars).
      Cilostazol is likely a cost-saving strategy (similar rate of TVR and lower
      costs). Sensitivity analysis showed that cilostazol is likely a dominant strategy
      (lower restenosis rate and costs, 85% dominant, 88.9% <1000 dollars per
      restenosis averted). CONCLUSIONS: Treatment with cilostazol is likely a cost
      saving or dominant strategy in patients with successful coronary bare metal stent
      implantation. Cilostazol may offer a low-cost alternative to restenosis
      prevention in patients who do not receive drug-eluting stents.

PMID- 16996858
TI  - Racial differences in reaching target low-density lipoprotein goal among
      individuals treated with prescription statin therapy.
AB  - BACKGROUND: Studies indicate that, overall, African Americans are less likely to
      achieve control of hyperlipidemia compared with whites. No population-based
      studies have examined the effect of race on achieving target low-density
      lipoprotein (LDL) goals among treated individuals. METHODS: Using computerized
      encounter and laboratory result data, we identified all African American and
      white patients in a Midwestern health system filling a statin prescription from
      January 1, 1997, through June 30, 2001 (index prescription), with no
      prescriptions filled 1 year before index prescription. We followed LDL results
      for 1 year after index prescription. RESULTS: A total of 16052 new statin users
      (32.5% African American) were identified. Mean baseline LDL was higher for
      African Americans (170.2 +/- 36.6) than for whites (161.8 +/- 37.2) (P < .001).
      Whites were more adherent to therapy, with 48.6% of white patients exposed to
      statins >80% of follow-up time (31.2% of African Americans) (P < .001). By the
      end of follow-up, 49.5% of African Americans and 71.1% of whites reached LDL
      goal. A proportional hazards model adjusting for age, sex, median household
      income, physician specialty, clinic site, baseline LDL, starting dose, and target
      LDL indicated that African Americans were less likely to reach goal compared with
      whites (hazard ratio 0.64, 95% CI 0.61-0.68). Results persisted after controlling
      for racial differences in statin adherence and LDL testing (hazard ratio 0.60,
      95% CI 0.57-0.63). CONCLUSIONS: African American patients initiating statin
      therapy are less likely to achieve LDL goal, even after controlling for adherence
      differences and other factors, suggesting that African Americans may require
      different pharmacologic management.

PMID- 16996860
TI  - Response of high-sensitivity C-reactive protein to exercise training in an at
      risk population.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hsCRP) is promoted as an
      independent predictor of atherosclerotic risk. In addition, cardiorespiratory
      fitness is inversely related to hsCRP in single-sex cross-sectional analyses. Our
      objective was to determine if modulating fitness with exercise training imposes
      changes in high-sensitivity C-reactive protein in a mixed-sex population at risk
      for cardiovascular disease. METHODS: We studied baseline and postintervention
      plasma hsCRP in 193 sedentary, overweight to mildly obese, dyslipidemic men and
      women who were randomized to 6 months of inactivity or 1 of 3 aerobic exercise
      groups: low amount-moderate intensity (energy equivalent of approximately 19.3
      km/wk at 40%-55% peak VO2), low amount-high intensity (energy equivalent of
      approximately 19.3 km/wk at 65%-80% peak VO2), or high amount-high intensity
      (energy equivalent of approximately 32.2 km/wk at 65%-80% peak VO2). RESULTS: At
      baseline, the study population was at intermediate to high cardiovascular risk as
      defined by hsCRP. Cardiorespiratory fitness was inversely related to hsCRP (P <
      .001) even after adjusting for significant and expected sex differences. Fitness,
      hormone replacement therapy use, and high-density lipoprotein cholesterol
      accounted for the sex difference in baseline hsCRP. Fitness, high-density
      lipoprotein cholesterol, fasting insulin, hormone replacement therapy, and
      visceral adiposity were all independent predictors for baseline hsCRP (r2 = 0.34
      for the entire model, P < .0001). However, despite significant improvements in
      fitness, visceral adiposity, subcutaneous adiposity, and insulin sensitivity,
      hsCRP did not change in response to exercise training (P > .20). CONCLUSIONS:
      Cardiorespiratory fitness is inversely related to hsCRP independent of sex and
      accounts for most of the large sex disparity in hsCRP. Nonetheless, in the
      absence of a significant change in diet, 6 months of aerobic exercise training
      does not produce a significant change in hsCRP in an at-risk population.

PMID- 16996859
TI  - Quality of cholesterol screening and management with respect to the National
      Cholesterol Education's Third Adult Treatment Panel (ATPIII) guideline in primary
      care practices in North Carolina.
AB  - BACKGROUND: Adherence to previous national cholesterol guidelines has been low.
      We assessed whether lipid screening and management was consistent with the
      National Cholesterol Education's ATPIII in a sample of primary care practices
      participating in a quality improvement study. METHODS: Demographic and clinical
      data were abstracted from charts of 5071 patients aged 21 to 84 years, which were
      seen between June 1, 2001, and May 31, 2003, at 60 practices. Clinical sites were
      non-university-based primary care practices from 22 North Carolina counties. A
      dyslipidemia screening test was defined as a lipid profile performed on persons
      when not on a lipid-lowering drug. Among patients receiving a lipid profile, the
      proportion of patients appropriately treated, per ATPIII, was calculated.
      Practice level variation in screening and management was examined using the 50th
      (20th and 80th) percentile values across practices. RESULTS: The median practice
      level dyslipidemia screening rate during the 2 years was 40.1% (25.8%, 53.7%) of
      their age-eligible patients. The appropriate decision regarding lipid-lowering
      therapy was documented within 4 months of the lipid profile for 79.3% (69.0%,
      86.0%) of practices' patients. Within 4 months, among the drug-ineligible
      patients, 100% (94%, 100%) were not prescribed drugs; 33.3% (6.3%, 50.0%) of the
      drug-eligible patients were prescribed lipid-lowering agents. CONCLUSIONS: The
      median dyslipidemia screening rate met the recommendations. There remains a need
      to improve the management of dyslipidemia; in particular, there was a significant
      underprescription of lipid-lowering drugs.

PMID- 16996861
TI  - Clinical correlates of long-term mortality after percutaneous interventions of
      saphenous vein grafts.
AB  - BACKGROUND: Increasing number of patients undergo percutaneous intervention of
      saphenous vein grafts (SVGs). However, the clinical factors associated with long
      term mortality after SVG interventions are currently less known. Accordingly, the
      goal of present study was to evaluate clinical correlates of long-term mortality
      and to develop a simple bedside tool for risk stratification in patients
      undergoing SVG interventions. METHODS: We analyzed 1019 patients undergoing SVG
      interventions from the Duke Cardiovascular Disease Database (1986-2003). Cox
      proportional hazards model was used to identify baseline variables associated
      with long-term mortality, and the model variables were then used to construct a
      nomogram for survival probability at 4 years. RESULTS: At a median follow-up of 4
      years, 24% of those undergoing SVG interventions died (interquartile range 2-7
      years). Independent correlates of death at follow-up on multivariable analysis
      included presenting heart rate (hazard ratio [HR] 1.02, 95% CI 1.01-1.03),
      diabetes (HR 1.73, 95% CI 1.37-2.18), presenting heart failure (HR 1.62, 95% CI
      1.27-2.06), age (per 10-year increase, HR 1.29, 95% CI 1.13-1.46), peripheral
      vascular disease (HR 1.59, 95% CI 1.23-2.04), renal insufficiency (HR 2.01, 95%
      CI 1.36-2.97), patent internal mammary graft (HR 0.67, 95% CI 0.53-0.86), body
      mass index < or = 25 kg/m2 (HR 0.91, 95% CI 0.85-0.97), carotid bruit (HR 1.44,
      95% CI 1.12-1.85), S3 ventricular gallop (HR 1.83, 95% CI 1.11-3.03), and
      hypertension (HR 1.38, 95% CI 1.04-1.83) (c-index 0.83). Bootstrap validation
      confirmed excellent internal validity of the model (mean c-index 0.84, 95% CI
      0.80-0.85). CONCLUSION: Long-term survival after SVG intervention is poor, with
      one fourth of patients dying at median follow-up of 4 years. The nomogram
      developed using the model variables provides a method for clinicians to advise
      patients undergoing SVG interventions regarding their long-term prognosis,
      thereby enhancing discharge and long-term follow-up planning and setting up of
      realistic expectations.

PMID- 16996862
TI  - A comparative analysis of short- and long-term outcomes after ventricular
      fibrillation out-of-hospital cardiac arrest in patients with ischemic and
      nonischemic heart disease.
AB  - Although ventricular fibrillation (VF) out-of-hospital cardiac arrest (OHCA)
      occurs primarily in the setting of severe ischemic heart disease (IHD), a
      significant proportion of events occurs in patients who do not have severe IHD.
      The relative effect of IHD on survival after VF OHCA is unknown. All residents of
      Rochester, Minnesota, who presented with a VF OHCA from November 1990 to December
      2004, treated by emergency medical services, were included in the study. During
      the study, emergency medical services treated 208 patients (64.1 +/- 13.6 years
      of age) for VF OHCA, with an average call-to-shock time of 6.3 +/- 1.8 minutes.
      Of these patients, 156 had IHD and 39 had non-IHD. In 13, the underlying heart
      disease was unknown. Eighty-seven patients (41.8%) survived to hospital discharge
      with neurologic recovery (66 with IDH [42%] vs 21 with non-IHD [54%], p =
      0.211)]. Five-year survival was 79 +/- 6% for patients with IHD versus 100% for
      those with non-IHD (p = 0.047). After adjustment for other patient
      characteristics, IHD was not predictive of 5-year survival (hazard ratio [HR]
      2.2, 95% confidence interval [CI] 0.7 to 9.8, p = 0.177). Variables associated
      with poor outcomes included age >65 years (HR 4.9, 95% CI 2.0 to 13.4, p =
      0.0003), ejection fraction <0.35% (HR 3.0, 95% CI 1.3 to 7.3, p = 0.012), and
      hypertension (HR 4.9, 95% CI 1.4 to 16.3, p = 0.001). In patients with IHD, use
      of an implantable cardioverter-defibrillator (HR 0.32, 95% CI 0.16 to 0.88, p =
      0.024) and statin therapy (HR 0.68, 95% CI 0.17 to 0.73, p = 0.001) were
      associated with decreased mortality. In conclusion, compared with patients with
      non-IHD, those with IHD had similar short- and long-term survival rates. Long
      term survival in patients with IHD was primarily influenced by other co-morbid
      conditions. Nonetheless, in patients with IHD, use of an implantable cardioverter
      defibrillator and statin therapy were associated with higher long-term survival
      rates.

PMID- 16996863
TI  - Relation between soluble intercellular adhesion molecule-1, statin therapy, and
      long-term risk of clinical cardiovascular events in patients with previous acute
      coronary syndrome (from PROVE IT-TIMI 22).
AB  - High levels of adhesion molecules, such as soluble intercellular adhesion
      molecule-1 (sICAM-1), are associated with long-term risk of cardiac events in
      patients with and without stable coronary artery disease. The relation between
      sICAM-1 and long-term risk after acute coronary syndromes (ACSs) and the
      influence of statin treatment has not been explored. Using a nested case-control
      design, patients with ACS who were enrolled in the PROVE IT-TIMI 22 trial were
      matched for age, gender, smoking, diabetes, type of ACS presentation, and
      revascularization for index event (583 patients with recurrent events vs 581
      controls). Patients with recurrent events were identified as such by death,
      myocardial infarction, or hospitalization for recurrent ACS. Soluble ICAM-1 was
      measured at study entry (approximately 7 days after ACS). After adjusting for
      statin regimen and other risk factors, patients in quartiles 2 to 4 were at a
      higher risk of clinical events compared with those in quartile 1 (odds ratio 1.6
      for quartile 4 vs 1, 95% confidence interval 1.1 to 2.3, p = 0.02). The risk of
      adverse events in patients with sICAM-1 levels in quartiles 2 to 4 was most
      marked in subjects who were allocated to standard dose statin therapy, even after
      adjusting for low-density lipoprotein cholesterol and C-reactive protein at day
      30. The risk in quartiles 2 to 4 was somewhat attenuated in the intensive therapy
      group. In conclusion, in this large study of patients with ACS, we provide
      evidence that increased endothelial activation after ACS is independently
      associated with increased long-term risk of death, myocardial infarction, or
      recurrent ACS.

PMID- 16996864
TI  - Usefulness of follow-up low-density lipoprotein cholesterol level as an
      independent predictor of changes of coronary atherosclerotic plaque size as
      determined by intravascular ultrasound analysis after statin (atorvastatin or
      simvastatin) therapy.
AB  - Using serial intravascular ultrasound (IVUS), we identified independent
      predictors of changes in coronary plaque size in relation to serum lipid levels.
      One hundred three patients with nonstenotic coronary plaques underwent baseline
      and 12-month follow-up IVUS studies; 54 patients (52%) were treated with statins.
      Standard IVUS analyses were performed. Baseline IVUS study showed no statistical
      differences in mean external elastic membrane, lumen, and plaque/media (P&M) area
      between statin-treated and nonstatin-treated patients. Although there was an
      increase in mean P&M cross-sectional area in nonstatin-treated patients, mean P&M
      cross-sectional area decreased in statin-treated patients (0.11 +/- 0.24 vs -0.20
      +/- 0.30 mm(2), p <0.001). There was a positive relation between changes in mean
      P&M area and follow-up low-density lipoprotein (LDL) cholesterol level (r =
      0.430, p <0.001), follow-up total cholesterol level (r = 0.365, p <0.001),
      changes in LDL cholesterol level (r = 0.312, p = 0.002), and changes in total
      cholesterol level (r = 0.252, p = 0.012). In multivariate linear regression
      analysis, the only independent predictor of changes in mean P&M area was follow
      up LDL cholesterol level (r = 0.469, p <0.001, 95% confidence interval 0.003 to
      0.006). The cut-off value of follow-up LDL cholesterol for no change or a
      decrease in mean P&M area was <100 mg/dl at regression analysis. In conclusion,
      the present 12-month follow-up IVUS study showed that follow-up LDL cholesterol
      level was the only independent predictor of changes in coronary plaque size. When
      patients achieved a follow-up LDL cholesterol level <100 mg/dl, regression or no
      progression of coronary plaque was expected. Aggressive lipid-lowering treatments
      with statins to decrease the follow-up LDL cholesterol level to <100 mg/dl are
      recommended.

PMID- 16996865
TI  - Comparison of coronary minimal lumen area quantification by sixty-four-slice
      computed tomography versus intravascular ultrasound for intermediate stenosis.
AB  - The present study assessed 64-slice computed tomographic accuracy to quantify
      minimal lumen area (MLA) and determine lesion severity in intermediate stenosis
      by angiography compared with intravascular ultrasound (IVUS). Sixty-four-slice
      computed tomography (CT) has been shown to be effective in coronary stenotic
      assessment by visual estimation compared with angiography. However, angiography
      is not an accurate gold standard for intermediate stenotic quantification
      compared with IVUS. Forty patients (54 lesions) with 30% to 70% coronary stenosis
      by angiography in a major coronary branch were included. All patients underwent
      quantitative angiography, retrospective electrocardiographically gated 64-slice
      CT (Siemens), and IVUS (40-MHz Atlantis; Boston Scientific). MLA was manually
      traced by 2 blinded and independent operators on 64-slice computed tomographic
      cross-sectional reconstruction and compared with IVUS MLA. A lesion was
      considered significant if the MLA was <or=6 mm(2) for the left main coronary
      artery and <or=4 mm(2) for another epicardial vessel with CT and IVUS. The
      correlation between IVUS MLA and computed tomographic MLA was r = 0.88 (p
      <0.001). Interobserver variabilities (mean +/- SD) were 1.2 mm(2) for CT and 1.1
      mm(2) for CT versus IVUS. Bland-Altman analysis showed a 95% confidence interval
      of -42% to +44% for computed tomographic measurement using IVUS as a reference.
      Sensitivity, specificity, accuracy, and Cohen's kappa coefficient for significant
      lesion classification using CT were 87%, 72%, 80%, and 0.6, respectively (p
      <0.0001). In conclusion, when using MLA, 64-slice CT was able to quantify
      coronary stenosis with good correlation compared with IVUS and determine lesion
      severity in patients with intermediate lesions by angiography.

PMID- 16996866
TI  - Comparison of sixty-four-slice multidetector computed tomographic coronary
      angiography to coronary angiography with intravascular ultrasound for the
      detection of transplant vasculopathy.
AB  - Coronary allograft vasculopathy (CAV) is the most important limitation to long
      term survival in adult heart transplant recipients and is difficult to detect
      without intravascular ultrasound (IVUS). We systematically evaluated the image
      quality of 64-slice multidetector computed tomographic (MDCT) coronary
      angiography in heart transplant recipients and tested the hypothesis that this
      modality is comparable to invasive coronary angiography with IVUS for the
      detection of CAV. Heart transplant recipients (n = 20) underwent invasive
      coronary angiography with IVUS and MDCT coronary angiography with a 64-slice
      scanner. Images were systematically analyzed for image quality and the presence
      of CAV. In addition, multidetector computed tomography and quantitative coronary
      angiography were used to measure lumen diameters at prespecified locations. Image
      quality analysis showed that, despite high mean heart rates (77 +/- 7 beats/min)
      and body mass index (29.5 +/- 5.3 kg/m(2)), 83% of coronary segments were graded
      as of excellent or good image quality. On average, 95 +/- 9% of the overall
      visualized length of the coronary arteries was imaged without motion artifacts,
      and the mean contrast-to-noise ratio was 11.3 +/- 4.6. Compared with IVUS,
      multidetector computed tomography had a sensitivity of 70%, specificity of 92%,
      positive predictive value of 89%, and negative predictive value of 77% for the
      detection of CAV. MDCT vessel diameter measurements correlated well with those
      obtained from quantitative coronary angiography (R(2) = 0.89). In conclusion, 64
      slice multidetector computed tomography provides good to excellent image quality
      in heart transplant recipients and has moderate to excellent test characteristics
      for the detection of CAV. Further, MDCT measurements of lumen diameters
      correlated well with quantitative coronary angiography.

PMID- 16996867
TI  - Prognostic usefulness of white blood cell count on admission and one-year outcome
      in patients with non-ST-segment elevation acute chest pain.
AB  - Little is known about the prognostic value of leukocyte count on admission for
      patients with chest pain. In total, 1,461 patients who presented to the emergency
      department with non-ST-segment elevation chest pain were studied by clinical
      history, electrocardiography, serial troponin I determination, and leukocyte
      count on admission. End points were 1-year mortality and major events (mortality
      or infarction). Overall patient distribution by quartiles of leukocyte count
      showed increased mortality (6%, 7%, 6%, and 17%, p = 0.0001) and major events
      (13%, 13%, 15%, and 24%, p = 0.0001) in the fourth quartile. After adjustment for
      other risk factors, the fourth quartile cut-off value (>10,000 cells/ml)
      predicted mortality (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p =
      0.0001) but not major events (p = 0.07). When analysis was performed to assess
      troponin status, in the subgroup with increased troponin (n = 634, 16%
      mortality), a leukocyte count >10,000 cells/ml was related to mortality (hazard
      ratio 2.2, 95% confidence interval 1.5 to 3.4, p = 0.0001). However, in the
      subgroup with normal troponin levels (n = 827, 4.2% mortality), there were no
      differences in mortality between patients with or without a leukocyte count
      >10,000 cells/ml (4.4% vs 4.2%, p = 0.8), with survival curves showing a tight
      overlap (p = 0.9). Further, in the subgroup with normal troponin levels,
      leukocyte count was not significantly different between patients with or without
      ST depression (7,969 +/- 2,171 vs 8,108 +/- 2,356 cells/ml, p = 0.6) and was not
      associated with mortality in patients with ST depression (p = 0.7). In
      conclusion, leukocyte count on admission is predictive of mortality in patients
      with chest pain and non-ST-segment elevation myocardial infarction. However, in
      the absence of myocardial necrosis, leukocyte count lacks prognostic value.

PMID- 16996868
TI  - Predictors of development of diabetes mellitus in patients with coronary artery
      disease taking antihypertensive medications (findings from the INternational
      VErapamil SR-Trandolapril STudy [INVEST]).
AB  - Knowledge of predictors of diabetes mellitus (DM) development in patients with
      coronary artery disease (CAD) who use antihypertensive therapy could contribute
      to decreasing this adverse metabolic consequence. This is particularly relevant
      because the standard of care, beta blockers combined with diuretics, may
      contribute to adverse metabolic risk. The INternational VErapamil SR-trandolapril
      STudy compared a calcium antagonist-based (verapamil SR) and a beta-blocker-based
      (atenolol) strategy with trandolapril and/or hydrochlorothiazide added to control
      blood pressure (BP) in patients with CAD. The 16,176 patients without DM at entry
      were investigated with regard to newly diagnosed DM during follow-up. Newly
      diagnosed DM was less frequent in the verapamil SR versus atenolol strategy (7.0%
      vs 8.2%, hazard ratio 0.85, 95% confidence interval 0.76 to 0.95, p <0.01).
      Characteristics associated with risk for newly diagnosed DM included United
      States residence, left ventricular hypertrophy, previous stroke/transient
      ischemic attack, Hispanic ethnicity, coronary revascularization,
      hypercholesterolemia, greater body mass index, and higher follow-up systolic BP.
      Addition of trandolapril to verapamil SR decreased DM risk and addition of
      hydrochlorothiazide to atenolol increased risk. In conclusion, clinical findings
      associated with more severe vascular disease and Hispanic ethnicity identify a
      group at high risk for developing DM, whereas lower on-treatment BP and treatment
      with verapamil SR-trandolapril attenuated this risk.

PMID- 16996869
TI  - Three-year clinical follow-up of the unrestricted use of sirolimus-eluting stents
      as part of the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital
      (RESEARCH) registry.
AB  - Sirolimus-eluting stents (SESs) have been shown to decrease restenosis compared
      with bare metal stents (BMSs). Currently, there are limited data on the long-term
      efficacy of these devices in a real-world patient population. Furthermore, the
      potential of a late restenotic phenomenon has not yet been excluded. From April
      to October 2002, 508 consecutive patients with de novo lesions exclusively
      treated with SESs were enrolled and compared with 450 patients treated with BMSs
      in the preceding 6 months (control group). Patients in the SES group more
      frequently had multivessel disease and type C lesions, received more stents, and
      had more bifurcation stenting. After 3 years, the cumulative incidence of major
      adverse cardiac events (comprising death, myocardial infarction, and target
      vessel revascularization) was significantly lower in the SES group compared with
      the pre-SES group (18.9% vs 24.7%, hazards ratio 0.73, 95% confidence interval
      0.56 to 0.96, p = 0.026). The 3-year risk of target lesion revascularization was
      7.5% in the SES group versus 12.6% in the pre-SES group (hazards ratio 0.57, 95%
      confidence interval 0.38 to 0.87, p = 0.01). In conclusion, the unrestricted use
      of SESs is safe and superior to the use of BMSs. The beneficial effects, reported
      after 1 and 2 years in reducing major adverse cardiac events, persisted with no
      evidence of a clinical late restenotic "catch-up" phenomenon.

PMID- 16996870
TI  - Effect of heparin on blood vascular endothelial growth factor levels in patients
      with ST-elevation acute myocardial infarction undergoing primary percutaneous
      coronary intervention.
AB  - It has been demonstrated that high blood vascular endothelial growth factor
      (VEGF) levels in patients with myocardial infarction decrease rapidly after
      reperfusion, possibly in response to heparin administration. We measured serum
      VEGF concentration before and after heparin infusion in 105 patients with ST
      elevation acute myocardial infarction (STEMI) who underwent primary percutaneous
      coronary intervention (PCI). Serum VEGF concentration in patients with STEMI was
      significantly higher than in healthy controls. After PCI, the concentration of
      VEGF decreased by approximately 70%, with the greatest decrease seen in patients
      with the highest initial VEGF levels. To determine whether heparin could decrease
      VEGF concentration by sequestering VEGF in the endothelium, a fixed dose of
      recombinant VEGF was incubated for 40 minutes with EA.hy926 endothelial cells in
      vitro. Recovery of VEGF from medium after culture was decreased by up to 15% with
      increasing doses of heparin. Concentration of VEGF did not change in the absence
      of heparin and/or endothelial cells. In conclusion, these results suggest that a
      rapid decrease in blood VEGF after PCI may be related to the administration of
      heparin, which binds simultaneously to VEGF and endothelial cells.

PMID- 16996871
TI  - Use of platelet glycoprotein IIb/IIIa inhibitors in saphenous vein graft
      percutaneous coronary intervention and clinical outcomes.
AB  - Platelet glycoprotein (GP) IIb/IIIa inhibitors are widely used in percutaneous
      coronary intervention (PCI). Previous studies have suggested that they do not
      offer benefit in saphenous vein graft PCI. Nonetheless, their use remains
      widespread during vein graft angioplasty. We retrospectively analyzed 1,537
      patients who underwent saphenous vein graft PCI. Patients who received a GP
      IIb/IIIa inhibitor (n = 941) were compared with those who did not receive any GP
      IIb/IIIa inhibitor (n = 596). The primary end point was myonecrosis after PCI
      (creatine kinase-MB level >3 times the upper reference limit). The incidence of
      myonecrosis after PCI was similar between the group that received GP IIb/IIIa and
      the group that did not (odds ratio for GP IIb/IIIa use 1.39, 95% confidence
      interval 0.97 to 2.00, p = 0.07). Propensity-adjusted analysis demonstrated no
      significant difference in myonecrosis after PCI, in-hospital mortality, Q-wave
      myocardial infarction, or bleeding (blood transfusion, retroperitoneal bleed, or
      hematoma) between the 2 groups. In an analysis restricted to patients who were
      treated with an emboli protection device, GP IIb/IIIa use was not associated with
      decreased myonecrosis after PCI (this was also the case for patients who were not
      treated with an emboli protection device). Unadjusted survival (mean follow-up
      5.5 +/- 0.1 years) was similar between the group that received GP IIb/IIIa and
      the group that did not (log-rank test, p = 0.89). There was no difference in
      survival after adjusting for the propensity to receive a GP IIb/IIIa inhibitor
      (adjusted odds ratio for GP IIb/IIIa use 0.92, 95% confidence interval 0.69 to
      1.23, p = 0.59). In conclusion, adjunctive use of platelet GP IIb/IIIa inhibitors
      in saphenous vein graft PCI does not appear to be associated with less
      myonecrosis or improved survival.

PMID- 16996872
TI  - Management and outcomes of coronary artery perforation during percutaneous
      coronary intervention.
AB  - Coronary perforation is a particularly feared complication of percutaneous
      coronary intervention. The optimal management and predictors of adverse outcomes
      for these patients remain to be defined. Advances in management such as the use
      of polytetrafluoroethylene-covered stents have not been critically examined in
      terms of efficacy. We analyzed a cohort of patients who sustained coronary
      perforation during percutaneous coronary intervention at our institution during a
      9-year period to examine the trends in incidence, management, and outcomes. The
      patient medical records were reviewed, and detailed angiographic analysis was
      undertaken to identify the predictors of adverse outcomes, including the
      development of tamponade, the requirement for emergency coronary artery bypass
      grafting, and in-hospital death. One year of follow-up was attempted for all
      patients. Seventy-two cases of coronary perforation were identified, with an
      overall incidence of 0.19%. The perforation grade and presence of chronic renal
      insufficiency were the only predictors of mortality on multivariate regression
      analysis. The use of polytetrafluoroethylene-covered stents to manage
      perforations was not associated with any reduction in adverse outcomes, such as
      the development of tamponade, the need for emergency coronary artery bypass
      grafting, or in-hospital death. In conclusion, coronary perforation remains a
      feared complication in the contemporary interventional era with significant in
      hospital mortality. Emphasis should be placed on preventing this complication
      whenever possible, including exercising particular caution in patients with
      chronic renal insufficiency. The treatment of such patients should be tailored to
      the severity of the perforation. The optimal treatment of these patients needs to
      be defined, and the efficacy of covered stents needs to be studied prospectively.

PMID- 16996873
TI  - Impact of percutaneous coronary intervention on the levels of interleukin-6 and C
      reactive protein in the coronary circulation of subjects with coronary artery
      disease.
AB  - Many clinical studies have evaluated the inflammatory response (mainly
      interleukin [IL]-6 and C-reactive protein [CRP]) after percutaneous coronary
      intervention (PCI) in patients with coronary artery disease (CAD). The aim of
      this study was to verify the source of possible elevation of IL-6 and CRP after
      PCI using coronary sinus sampling. We studied 87 subjects who underwent coronary
      angiography for diagnostic, therapeutic, or follow-up purposes. Blood samples
      were taken by the PCI team during the catheterization study from the coronary
      sinus. We measured coronary IL-6 levels by sandwich enzyme-linked immunosorbent
      assay, and high-sensitivity CRP levels were measured by latex immunonephelometry.
      The subjects were then classified according to their coronary angiographic
      findings into non-CAD (no evidence of significant organic CAD), mild CAD (1
      vessel narrowed), and severe CAD (>or=2 vessels narrowed) groups. PCI (including
      stent deployment) was performed in 16 patients with CAD. The mean coronary IL-6
      value was higher in the severe than in the mild CAD group (3.67 +/- 2.48 vs 2.3
      +/- 1.15 pg/ml, p = 0.027). The mean coronary IL-6 value was higher in the
      subjects who underwent PCI than in those who did not (2.9 +/- 1.23 vs 1.87 +/-
      0.9 pg/ml, p = 0.037), and the same was found regarding CRP (1.244 +/- 0.72 vs
      0.498 +/- 0.51 mg/L, p = 0.032). The coronary IL-6 values correlated positively
      with the coronary CRP values (r = 0.374, p = 0.017). In conclusion, the increase
      in coronary IL-6 and CRP levels after PCI in patients with CAD might be
      attributed to their release from the coronary atheroma secondary to the direct
      mechanical effect applied on the atheroma itself by balloon inflation and stent
      deployment.

PMID- 16996874
TI  - Clinical and angiographic outcomes after placement of multiple overlapping drug
      eluting stents in diffuse coronary lesions.
AB  - Multiple overlapping drug-eluting stents have increasingly been used to treat
      diffuse coronary disease, but the safety and efficacy of this approach remains
      unclear. We assayed the clinical and angiographic outcomes after placement of
      "full metal jacket" stents (stented length >or=60 mm) in 347 consecutive patients
      (352 lesions) with very long de novo coronary lesions. Mean age was 61.0 +/- 10.1
      years, and the mean stented length was 71.9 +/- 13.7 mm. The procedural success
      rate was 97.7%. Major in-hospital complications (1 death, 2 cases of acute stent
      thrombosis) occurred in 3 patients (0.7%). Angiographic follow-up data, obtained
      for 230 (234 lesions) of the 328 eligible patients (70.1%), showed that the
      restenosis rate was 13.7%. Multivariate analysis found that the reference artery
      diameter (odds ratio 0.05, 95% confidence interval [CI] 0.01 to 0.33, p = 0.002)
      and the use of Taxus stents (odds ratio 2.88, 95% CI 1.03 to 8.04, p = 0.043)
      were significant predictors of restenosis. During follow-up (16.6 +/- 6.9
      months), 9 deaths (6 cardiac and 3 noncardiac), 1 nonfatal myocardial infarction,
      and 13 target lesion revascularizations occurred. The cumulative probability of
      survival without major adverse cardiac events (cardiac death, Q-wave myocardial
      infarction, and target lesion revascularization) was 95.4 +/- 1.1% and 91.4 +/-
      2.1% at 1 and 2 years, respectively. Left ventricular dysfunction (ejection
      fraction <45%) was the only predictor of stent thrombosis (hazard ratio 18.24,
      95% CI 1.65 to 201.19, p = 0.018) and cardiac death/Q-wave myocardial infarction
      (hazard ratio 5.37, 95% CI 1.28 to 22.49, p = 0.021). In conclusion, full metal
      jacket drug-eluting stents may be a safe and effective method to treat diffuse
      coronary disease and may be a useful treatment option for complex long lesions.

PMID- 16996875
TI  - Comparison of mortality rates in statin users versus nonstatin users in a United
      States veteran population.
AB  - Statins have been shown to be effective in reducing cardiovascular events and
      overall mortality in primary and secondary prevention trials. This study was
      designed to examine the effect of statin use on overall death. Cross-sectional
      data were obtained from the Department of Veterans Affairs Veterans Integrated
      Service Network 16 database for approximately 1.5 million veterans followed up in
      10 hospitals in the southern United States. Statins were prescribed more often to
      elderly subjects with a history of coronary artery disease, hypertension,
      diabetes mellitus, current smoking, and using cardiovascular drugs (beta
      blockers, aspirin, angiotensin-converting enzyme inhibitors, and calcium channel
      blockers). The predictors of death were, as expected, cancer, diabetes mellitus,
      the use of cardiac drugs, and age. Importantly, using statins showed a highly
      significant negative association with death (odds ratio 0.54, 95% confidence
      interval 0.42 to 0.69, p <0.0001), even after adjustment for all other variables.
      Overall, the mean age at death among statin users was 2 years older than among
      nonstatin users, despite statin users being at a higher risk of death. In
      conclusion, the results of this study have shown that using statins is a potent
      life-saving strategy. The benefit observed in this study is unique because almost
      1/2 the patients were >or=70 years of age when statin therapy was initiated.

PMID- 16996876
TI  - Determinants of sudden cardiac death in patients with persistent atrial
      fibrillation in the rate control versus electrical cardioversion (RACE) study.
AB  - This report evaluated the correlates of sudden cardiac and nonsudden cardiac
      death in patients with persistent atrial fibrillation randomized to rate or
      rhythm control in the RAte Control vs Electrical cardioversion (RACE) study.
      Sudden cardiac death was observed in 16 patients, 8 patients in each group.
      Previous myocardial infarction resulted in a 4.9-fold increased risk of sudden
      death (95% confidence interval 1.8 to 13.2). The use of beta blockers showed
      their protective nature (hazard ratio 0.2, 95% confidence interval 0.05 to 0.9).
      The randomized treatment strategy, heart rhythm during follow-up, use of
      antiarrhythmic drugs, and number of stroke risk factors were not associated with
      sudden cardiac death. In conclusion, the treatment of underlying disease, rather
      than the heart rhythm, seems essential to prevent mortality.

PMID- 16996877
TI  - Distribution and prognostic significance of QT intervals in the lowest half
      centile in 12,012 apparently healthy persons.
AB  - The presence of an abnormally short QT interval has been noted among survivors of
      idiopathic ventricular fibrillation and among close relatives of victims of
      unexplained sudden death. Most reported cases have had rate-corrected QT (QTc)
      intervals of <300 ms. The prevalence of such values in the community has not been
      documented. We reviewed the electrocardiograms (ECGs) of 12,012 subjects who
      underwent routine medical examinations for occupational reasons. The QT interval
      was measured by 2 physicians in all cases, and QTc interval was calculated. All
      ECGs with QTc values in the lowest 5% were reviewed by 2 cardiologists expert in
      QT analysis, and the QT measurement was corrected if necessary. Information about
      subsequent survival was obtained from the case file or from public records. In
      the lowest 1/2 centile, the distribution of QTc values continued to follow a
      normal pattern without evidence of a distinct subpopulation of low values. The
      shortest QTc encountered was 335 ms. Information about subsequent survival was
      available for 36 of the 60 subjects with the lowest 1/2 centile of QTc values.
      None of these subjects died during the 7.9 +/- 4.5 years subsequent to the ECG
      that demonstrated the short QT interval. In conclusion, a QTc interval of <or=330
      ms is extremely rare in healthy subjects, and the presence of a QT interval in
      the lowest 1/2 centile of the normal range does not imply a significant risk of
      sudden death.

PMID- 16996878
TI  - Reevaluation of the criterion for interatrial block.
AB  - The importance of the interatrial block has often been overshadowed by the debate
      on the appropriate cutoff to define its excessively wide P waves. However, by
      far, most publications have accepted P waves of >or=110 ms to represent abnormal
      interatrial conduction on the electrocardiogram. These "guidelines" have been
      structured on anachronistic electrocardiographic standards mostly determined from
      references to earlier textbooks and other publications that often did not involve
      original work. As such, reevaluation of the top normal value for the P-wave
      duration in adults is probably long overdue. We reevaluated the prevalence of
      interatrial block in our previously published series of 500 outpatients using
      existing standards for normal P-wave values and compared these results with the
      previous known prevalence of interatrial block to generate this present report.
      In conclusion, the frequency of the mode duration for P waves (120 ms) suggests
      electrophysiologic reevaluation of the normal range.

PMID- 16996879
TI  - Peak systolic blood pressure on a graded maximal exercise test and the blood
      pressure response to an acute bout of submaximal exercise.
AB  - Blood pressure (BP) is immediately reduced after aerobic exercise (postexercise
      hypotension [PEH]). Whether peak systolic BP on a maximal graded exercise stress
      test (GEST) relates to PEH is not known. This study examined associations between
      peak systolic BP on a GEST and PEH. Subjects were 50 men (mean +/- SEM age 43.8
      +/- 1.3 years) with elevated BP (145.3 +/- 1.5/85.9 +/-1.1 mm Hg). Men completed
      a GEST and 3 experiments: nonexercise control and 2 cycle bouts at 40% (LIGHT)
      and 60% (MODERATE) of maximal oxygen consumption. After the experiments, subjects
      left the laboratory wearing ambulatory BP monitors. Peak systolic BP on a GEST
      was categorized into tertiles: low (n = 17, 197.4 +/- 2.0 mm Hg), medium (n = 16,
      218.4 +/- 1.4 mm Hg), and high (n = 17, 248.9 +/- 2.8 mm Hg). Repeated-measures
      analysis of variance tested if BP differed over time and among experimental
      conditions and peak systolic BP groups. In men with high peak systolic BP,
      systolic BP was reduced by 7.3 +/- 2.6 mm Hg after LIGHT and by 5.0 +/- 2.2 mm Hg
      after MODERATE compared with nonexercise control over 10 hours, with the more
      apparent effects seen after LIGHT (p <0.05). In men with low peak systolic BP,
      systolic BP was reduced by 6.3 +/- 2.3 mm Hg after MODERATE compared with
      nonexercise control over 10 hours (p <0.05). In men with medium peak systolic BP,
      systolic BP was not different after exercise compared with nonexercise control
      over 10 hours (p >or=0.05). Men with high peak systolic BP had decreased systolic
      BP to the greatest extent after LIGHT, whereas men with low peak systolic BP
      reduced systolic BP after MODERATE. In conclusion, the findings of this study
      suggest that peak systolic BP on a GEST may be used to characterize which men
      with hypertension will have decreased systolic BP after acute submaximal aerobic
      exercise.

PMID- 16996880
TI  - The obesity paradox: fact or fiction?
AB  - Although the adverse health consequences of obesity in the general population
      have been well documented, recent evidence suggests that obesity is associated
      with better outcomes in patients with heart failure (HF). Studies of patients
      with HF that specifically examined the impact of body mass index (BMI) on
      outcomes have suggested the existence of an "obesity paradox." However, closer
      examination of these studies raises important questions on the validity of the
      paradox. First, the diagnosis of HF in obese patients, particularly when made
      using clinical variables, may not be accurate; the obese patients in these
      studies may actually be "healthier" than their nonobese comparators. Second, the
      deleterious effects of cachexia, rather than the salutary ones of obesity, are
      likely the main reason for the inverse correlation between BMI and HF outcome,
      especially once the underlying biologic mechanisms behind cachexia and obesity in
      patients with HF are considered. Furthermore, few studies have specifically
      examined the more severely obese population (BMI >35 kg/m(2)) when assessing
      outcomes, and those that have suggest that severely obese patients may have worse
      outcomes than patients with normal weights or those who are mildly obese.
      Therefore, a "U-shaped" outcome curve according to BMI for patients with HF may
      actually exist, in which mortality is greatest in cachectic patients; lower in
      normal, overweight, and mildly obese patients; but higher again in more severely
      obese patients. Further prospective studies assessing the impact of more marked
      degrees of obesity on outcomes in patients with HF are needed to more
      conclusively determine whether the obesity paradox truly exists.

PMID- 16996881
TI  - Velocity vector imaging to quantify ventricular dyssynchrony and predict response
      to cardiac resynchronization therapy.
AB  - Velocity vector imaging is a novel quantitative echocardiographic technique that
      was applied to routine grayscale echocardiographic images of 23 patients with
      heart failure who underwent cardiac resynchronization therapy. The hypothesis was
      tested that velocity vector imaging can quantify left ventricular mechanical
      dyssynchrony and predict response to resynchronization therapy. Tissue velocities
      were determined by the automated tracking of periodic B-mode image patterns on
      digital cine loops from standard apical 4-chamber, 2-chamber, and long-axis
      views, with the user tracing the mid left ventricular wall from a single frame.
      Dyssynchrony was determined as the greatest opposing wall peak longitudinal
      systolic velocity delay from the 3 views. Responders, defined as those with
      >or=15% increases in the ejection fraction, had greater baseline dyssynchrony
      than nonresponders (opposing wall velocity delays of 131 +/- 83 vs 52 +/- 60 ms,
      p <0.05), and >or=75 ms predicted response with 85% sensitivity and 80%
      specificity when followed 8 +/- 5 months after resynchronization therapy.
      Baseline electrocardiographic QRS duration was not predictive in the same
      patients. In conclusion, echocardiographic velocity vector imaging has potential
      for clinical utility.

PMID- 16996882
TI  - Significance of left atrial contractile function in asymptomatic subjects with
      hereditary hemochromatosis.
AB  - Patients with hereditary hemochromatosis (HH) have been reported to develop
      diastolic functional abnormalities detectable by echocardiography, but it is
      unknown whether these occur in asymptomatic subjects. Thus, this study tested
      whether echocardiographic left ventricular (LV) relaxation abnormalities are
      detectable in subjects with asymptomatic HH. Forty-three asymptomatic subjects
      with HH (C282Y homozygosity in the HFE gene) and 21 age- and gender-matched
      control subjects without known HFE mutations underwent echocardiography with
      comprehensive diastolic functional evaluations. Subjects with HH were in New York
      Heart Association functional class I and consisted of 22 newly diagnosed patients
      (group A) and 21 chronically phlebotomized subjects with stable iron levels
      (group B). Group A subjects showed significant iron overload compared with group
      B subjects and controls (group C) (ferritin 1,164 +/- 886 [p <0.05 vs groups B
      and C], 128 +/- 262, and 98 +/- 76 microg/L and transferrin saturation 79 +/- 19%
      [p <0.05 vs groups B and C], 42 +/- 21%, and 26 +/- 10% for groups A, B, and C,
      respectively). Echocardiographic evaluation revealed (1) no statistically
      significant abnormalities of Doppler LV relaxation in HH groups; (2) significant
      augmentation of atrial contractile function in subjects with HH compared with
      controls, which was not correlated with iron levels and treatment status; and (3)
      the preservation of overall LV systolic function in HH groups. In conclusion, the
      results of this study suggest that the augmentation of atrial contraction appears
      to be an early detectable echocardiographic cardiac manifestation of abnormal
      diastolic function in asymptomatic subjects with HH, which may reflect
      undetectable subclinical LV relaxation abnormalities.

PMID- 16996883
TI  - Prognostic significance of left atrial size in patients with hypertrophic
      cardiomyopathy (from the Italian Registry for Hypertrophic Cardiomyopathy).
AB  - This study assessed left atrial (LA) dimension as a potential predictor of
      outcome in hypertrophic cardiomyopathy (HC). From the Italian Registry for
      Hypertrophic Cardiomyopathy, 1,491 patients (mean age 47 +/- 17 years; 61% men;
      19% obstructive), followed for 9.4 +/- 7.4 years after the initial
      echocardiographic evaluation, constituted the study group. The mean LA transverse
      dimension was 43 +/- 9 mm and was larger in patients with severe symptoms (48 +/-
      9 mm for New York Heart Association classes III and IV vs 42 +/- 9 mm for classes
      I and II, p <0.001), atrial fibrillation (47 +/- 9 vs 42 +/- 8 mm in sinus
      rhythm, p <0.001), and left ventricular outflow obstruction (46 +/- 9 mm for
      >or=30 mm Hg at rest vs 42 +/- 9 mm for <30 mm Hg at rest, p <0.001). On
      univariate analysis, each 5-mm increase in LA size was associated with a hazard
      ratio (HR) of 1.2 for all-cause mortality (p <0.0001). On multivariate analysis,
      a LA dimension >48 mm (the 75th percentile) had a HR of 1.9 for all-cause
      mortality (p = 0.008), 2.0 for cardiovascular death (p = 0.014), and 3.1 for
      death related to heart failure (p = 0.008) but was unassociated with sudden death
      (p = 0.81). Similar results were obtained after the exclusion of patients with
      atrial fibrillation (HR 1.7, p = 0.008) or outflow obstruction (HR 1.8, p =
      0.003). The predictive power of LA dimension >48 mm was also validated in an
      independent HC cohort from the United States, with similar HRs (1.8 for all-cause
      mortality, p = 0.019). In conclusion, in a large cohort of patients with HC from
      a nationwide registry, a marked increase in LA dimension were predictive of long
      term outcome, independent of co-existent atrial fibrillation or outflow
      obstruction. LA dimension is a novel and independent marker of prognosis in HC,
      particularly relevant to the identification of patients at risk for death related
      to heart failure.

PMID- 16996884
TI  - Comparison of feasibility and accuracy of transthoracic echocardiography versus
      computed tomography in patients with known ascending aortic aneurysm.
AB  - Aortic valve diseases, hypertension, and connective tissue disorders may be
      causes of ascending aortic aneurysms. Aortic enlargement monitoring is essential
      for surgical timing and for operative design. In this regard, several imaging
      techniques may have limitations: magnetic resonance is not widespread and is
      expensive, computed tomography uses radiation, and transesophageal
      echocardiography is a semi-invasive method. The aim of this study was to analyze
      the feasibility of transthoracic echocardiography in the evaluation of aortic
      dimensions and its accuracy in comparison with multidetector computed tomography.
      In 44 patients with known ascending aortic aneurysms, transthoracic
      echocardiographic and computed tomographic measurements were obtained and
      compared at different levels: the annulus, sinuses of Valsalva, sinotubular
      junction, ascending aorta, and aortic arch. Transthoracic echocardiographic
      diameters were obtained in all patients, apart from the aortic arch, which was
      measured in 40 cases. Transthoracic echocardiographic and computed tomographic
      diameters correlated significantly (p <0.001), with very small SEEs: for the
      annulus, r = 0.846 (SEE 0.37); for the sinuses of Valsalva, r = 0.967 (SEE 0.35);
      for the sinotubular junction, r = 0.965 (SEE 0.33); for the ascending aorta, r =
      0.976 (SEE 0.41); and for the aortic arch, r = 0.87 (SEE 0.50). In conclusion,
      transthoracic echocardiography is a feasible and accurate technique for the
      assessment and follow-up of thoracic aortic diameters in patients with ascending
      aortic aneurysms.

PMID- 16996885
TI  - Differences of lateral and septal mitral annulus velocity by tissue Doppler
      imaging in the evaluation of left ventricular diastolic function.
AB  - Left ventricular diastolic dysfunction (LVDD) was investigated in 276 outpatients
      at a university cardiology practice by tissue Doppler imaging of mitral valve
      annular velocity. The well-investigated parameters of mitral inflow were used as
      the standard. Using septal E/Ea ratios, 62 patients (22%) had no LVDD, 44
      patients (16%) had mild LVDD, 126 patients (46%) had moderate LVDD, 25 patients
      (9%) had severe LVDD, and 19 patients (7%) had indeterminate LVDD. Using lateral
      E/Ea ratios, 131 patients (48%) had no LVDD, 40 patients (14%) had mild LVDD, 62
      patients (22%) had moderate LVDD, 9 patients (3%) had severe LVDD, and 12
      patients (13%) had indeterminate LVDD. In conclusion, the use of septal tissue
      Doppler imaging tends to overestimate the severity of LVDD compared with the use
      of lateral tissue Doppler imaging.

PMID- 16996886
TI  - Right ventricular systolic function is not the sole determinant of tricuspid
      annular motion.
AB  - Maximal tricuspid annular plane systolic excursion (TAPSE) correlates well with
      right ventricular (RV) function; however, little is known regarding the impact of
      left ventricular (LV) systolic function on TAPSE. Consequently, TAPSE was
      examined in 206 patients (105 men; mean age 56 +/- 17 years), and the data were
      analyzed with respect to RV (RV fractional area change 45 +/- 19%) and LV (56 +/-
      17%) systolic function. The mean TAPSE for the population studied was 1.97 +/-
      0.72 cm. Although a strong linear correlation was noted between RV fractional
      area change and TAPSE (r = 0.73, p <0.0001), relative differences with regard to
      TAPSE were also found. First, the greatest TAPSE was noted only when RV and LV
      systolic function were normal (2.46 +/- 0.50 cm). Second, patients with reduced
      RV systolic function had the smallest TAPSE (1.28 +/- 0.48 cm, p <0.0001). Third,
      patients with normal RV function but reduced LV systolic function had TAPSE (1.91
      +/- 0.54 cm, p <0.0001) that was intermediate between that of patients with
      normal RV and LV systolic function and those with abnormal RV systolic function.
      Fourth, patients with reduced biventricular function had the smallest TAPSE (1.16
      +/- 0.41 cm, p <0.0001). In conclusion, TAPSE is not only determined by RV
      systolic function but also appears to depend on LV systolic function. TAPSE <2.0
      cm is associated with some degree of either RV or LV dysfunction, whereas a value
      >2.0 cm suggests normal biventricular systolic function.

PMID- 16996887
TI  - Comparison of the amplitude of the P-wave from intracardiac electrocardiogram
      obtained by means of a central venous catheter filled with saline solution to
      that obtained via esophageal electrocardiogram.
AB  - Recognition of the P wave is important for the correct characterization of atrial
      and ventricular arrhythmias. When the P wave is difficult to identify on standard
      electrocardiography (SECG), either esophageal electrocardiography (EECG) or
      intracardiac electrocardiography (IC-ECG), central venous catheter may be used.
      The feasibility of these methods has already been demonstrated, but there is no
      published study comparing them. This study compared the amplitude of the P wave
      obtained by IC-ECG with those of the P waves obtained by EECG and SECG. SECG,
      EECG, and IC-ECG were performed on each patient. IC-ECG and EECG made it possible
      to register P waves larger than registered by SECG (p <0.00001). The difference
      between the largest P waves obtained with IC-ECG (5.93 +/- 3.56 mm) and EECG
      (4.67 +/- 2.16 mm) was not statistically significant (p = 0.1953). In conclusion,
      IC-ECG is easy to perform and magnifies the P wave at least as effectively as
      EECG.

PMID- 16996888
TI  - Metabolic syndrome and hyperglycemia: congruence and divergence.

PMID- 16996889
TI  - Giant coronary artery aneurysm causing superior vena cava syndrome and congestive
      heart failure.
AB  - Coronary artery aneurysms are defined as localized coronary artery dilations >1.5
      times the diameter of the adjacent segments. In adults, they are commonly of
      atherosclerotic origin and are usually asymptomatic. This is the first case
      report of a coronary artery aneurysm causing superior vena cava syndrome and
      heart failure. Chest x-ray showed cardiomegaly, and transthoracic
      echocardiography showed a mass that was confirmed by transesophageal
      echocardiography, computed tomography, and coronary angiography. In conclusion,
      giant coronary artery aneurysms can cause superior vena cava syndrome.

PMID- 16996891
TI  - Patent foramen ovale and migraine.

PMID- 16996892
TI  - C-reactive protein and lone atrial fibrillation: potential confounders.

PMID- 16996893
TI  - The role of patient-centered outcomes in defining the clinical course of chronic
      obstructive pulmonary disease. Introduction.

PMID- 16996894
TI  - The value of forced expiratory volume in 1 second decline in the assessment of
      chronic obstructive pulmonary disease progression.
AB  - Forced expiratory volume in 1 second (FEV1) declines normally with aging by
      approximately 30 mL/yr, but in susceptible smokers, the decline is greater (about
      60 mL/yr), resulting in the development of chronic obstructive pulmonary disease
      (COPD). Smoking cessation usually restores the normal or near-normal rate of FEV1
      decline, whereas intermittent quitting provides less benefit. Thus, smoking
      cessation is a critical component for the prevention of COPD progression. FEV1 is
      central to the definition of COPD and classification of its severity. FEV1 is a
      good predictor of exercise tolerance and correlates with survival and quality of
      life. More rapid FEV1 decline is also predictive of morbidity, mortality, and
      hospitalization rates. Risk factors for accelerated decline in FEV1, in addition
      to smoking, include frequent exacerbations, airways reactivity, and possibly
      chronic systemic inflammation. Genetic components of the decline in FEV1 are
      being actively explored, but none has been extensively validated other than
      alpha1-antitrypsin deficiency. To date, only smoking cessation has been
      definitively shown to be effective in reducing the rate of FEV1 decline, but
      other therapeutic strategies are under active research. Consequently, FEV1 and
      its change over time are important outcomes in COPD and valuable measures for the
      assessment of disease progression.

PMID- 16996895
TI  - Impact of chronic obstructive pulmonary disease on quality of life: the role of
      dyspnea.
AB  - Dyspnea is a common symptom that accompanies a diagnosis of chronic obstructive
      pulmonary disease (COPD). Dyspnea often interferes with the patient's health
      related quality of life (HRQOL), yet it is often underreported by the patient and
      underrecognized by the clinician. Reductions in objective pulmonary function
      measurements, such as forced expiratory volume in 1 second, are not well
      correlated with the patient's perception of symptoms and HRQOL. The patient's
      self-reported or subjective assessment is therefore important when evaluating the
      intensity of dyspnea and its impact on HRQOL. This article describes several well
      validated questionnaires and dyspnea assessment scales that can be effective for
      assessing the intensity and impact that dyspnea may have on patient-perceived
      HRQOL. In addition, it describes the integration of pulmonary rehabilitation and
      specific pharmacotherapies as well as how these interventions can positively
      influence and modify the severity and distress of dyspnea. Effective assessment
      and therapeutic management of dyspnea for the patient living with COPD are
      opportunities to improve the patient's overall HRQOL.

PMID- 16996896
TI  - The connection between chronic obstructive pulmonary disease symptoms and
      hyperinflation and its impact on exercise and function.
AB  - Forced expiratory volume in 1 second (FEV1) has served as an important diagnostic
      measurement of chronic obstructive pulmonary disease (COPD) but has not been
      found to correlate with patient-centered outcomes such as exercise tolerance,
      dyspnea, or health-related quality of life. It has not helped us understand why
      some patients with severe FEV1 impairment have better exercise tolerance compared
      with others with similar FEV1 values. Hyperinflation, or air trapping caused by
      expiratory flow limitation, causes operational lung volumes to increase and even
      approach the total lung capacity (TLC) during exercise. Some study findings
      suggest that a dyspnea limit is reached when the end-inspiratory lung volume
      encroaches within approximately 500 mL of TLC. The resulting limitation in daily
      physical activity establishes a cycle of decline that includes physical
      deconditioning (elevated blood lactic acid levels at lower levels of exercise)
      and worsening dyspnea. Hyperinflation is reduced by long-acting bronchodilators
      that reduce airways resistance. The deflation of the lungs, in turn, results in
      an increased inspiratory capacity. For example, the once-daily anticholinergic
      bronchodilator tiotropium increases inspiratory capacity, 6-minute walk distance,
      and cycle exercise endurance time, and it decreases isotime fatigue or dyspnea.
      Pulmonary rehabilitation and oxygen therapy both reduce ventilatory requirements
      and improve breathing efficiency, thereby reducing hyperinflation and improving
      exertional dyspnea. Thus, hyperinflation is directly associated with patient
      centered outcomes such as dyspnea and exercise limitation. Furthermore,
      therapeutic interventions--including pharmacotherapy and lung volume--reduction
      surgery--that reduce hyperinflation improve these outcomes.

PMID- 16996897
TI  - Functional status and quality of life in chronic obstructive pulmonary disease.
AB  - Exertional dyspnea often causes patients with chronic obstructive pulmonary
      disease (COPD) to unconsciously reduce their activities of daily living (ADLs) to
      reduce the intensity of their distress. The reduction in ADLs leads to
      deconditioning which, in turn, further increases dyspnea. Both dyspnea and
      fatigue are important factors affecting health-related quality of life (HRQOL).
      The functional status of patients relates to how well they perform ADLs.
      Activities, however, may not be severely limited until the disease becomes
      advanced. The elimination of an ADL depends on the necessity or desirability of
      that activity and the intensity of the associated symptoms. HRQOL is measured
      using symptoms, functional status, and a rating of their impact on the
      individual. The Pulmonary Functional Status Scale (PFSS) and the Pulmonary
      Functional Status and Dyspnea Questionnaire (PFSDQ) are 2 COPD-specific
      functional status questionnaires. Pedometers or accelerometers can quantify the
      levels of activity of patients with COPD. HRQOL is measured with validated
      multidimensional questionnaires that cover symptoms, physical, psychological, and
      social domains. Ideally, these instruments are discriminative (i.e., separate
      degrees of impairment) and evaluative (i.e., detect small changes after therapy).
      HRQOL questionnaires may be generic (e.g., Medical Outcomes Study Short Form-36
      [SF-36]) and can measure favorable changes after intervention, such as pulmonary
      rehabilitation, or they can be disease specific with disease-related domains,
      e.g., Chronic Respiratory Disease Questionnaire (CRQ) with domains of dyspnea,
      fatigue, emotion, and mastery; and St. George's Respiratory Questionnaire (SGRQ)
      with domains of symptoms, activity, and psychosocial impact. A case is presented
      that depicts how these tools may be used to evaluate improvement with
      intervention in a patient with COPD.

PMID- 16996898
TI  - The impact of severe exacerbations on quality of life and the clinical course of
      chronic obstructive pulmonary disease.
AB  - Severe exacerbations of chronic obstructive pulmonary disease (COPD) are morbid
      events with slow recovery periods. They consume substantial healthcare resources,
      and they may cause a more rapid reduction in lung function over time. Quality of
      life (QOL) deteriorates in patients who experience exacerbations, and the more
      frequent the exacerbations, the more rapid the decline in QOL. Hospitalizations
      due to exacerbations account for up to 70% of the cost of medical care for
      patients with COPD. Patients with more severe COPD have more hospitalizations
      compared with those with less severe disease. A number of therapeutic
      interventions reduce the number of exacerbations and hospitalizations due to
      respiratory disease. The long-acting anticholinergic bronchodilator tiotropium,
      influenza vaccination, and possibly case management appear to reduce need for
      hospitalization substantially. COPD management should include drugs and other
      interventions that reduce the frequency of exacerbations and minimize their
      negative impact on the clinical course of the disease.

PMID- 16996899
TI  - Clinical course of chronic obstructive pulmonary disease: review of therapeutic
      interventions.
AB  - Chronic obstructive pulmonary disease (COPD) is a preventable and treatable
      disease in which patients experience a progressive decline in lung function.
      Based on clinical evidence, the management of COPD should focus on (1) earlier
      diagnosis; (2) risk reduction through smoking cessation, decreased exposure to
      inhaled irritants, and immunization against respiratory pathogens; (3) symptom
      reduction with pharmacotherapy and pulmonary rehabilitation; (4) decreasing
      complications by reducing exacerbations and improving pulmonary function; and (5)
      improving health-related quality of life (HRQOL). Smoking cessation has been
      shown to slow lung function decline and to reduce mortality--including deaths due
      to lung cancer, other respiratory disease (including COPD), and cardiovascular
      disease. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) and
      the American Thoracic Society and European Respiratory Society (ATS/ERS)
      guidelines advocate interventions according to the severity of COPD and recommend
      initiation of maintenance long-acting bronchodilator therapy in patients with
      moderate disease. However, recent evidence from a post hoc analysis of randomized
      controlled trials of tiotropium suggests that initiation of long-acting
      bronchodilator therapy at earlier stages of disease may also provide improvements
      in lung function and HRQOL. The results of ongoing long-term studies may soon
      provide evidence that in addition to relieving symptoms and improving patient
      HRQOL, specific pharmacologic therapies may also alter the clinical course of
      COPD.

PMID- 16996900
TI  - Surrogates of mortality in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) remains a leading cause of
      disability and death in the United States. The identification and amelioration of
      systemic manifestations of COPD may improve long-term outcomes, including
      survival. These systemic manifestations often correlate with increased risk of
      mortality and may be considered surrogates of disease severity. Several potential
      clinical surrogates are evaluated, including airflow obstruction, dyspnea,
      malnutrition, hypoxemia, exercise capacity, lung hyperinflation, and anemia. The
      evidence in support of the impact of various COPD treatment modalities on
      systemic manifestations of COPD is also reviewed. Finally, the usefulness of
      measuring body mass index, degree of airflow obstruction, dyspnea, and exercise
      capacity in combination (the BODE index), as a measure of disease severity and
      mortality risk in COPD, is examined and found to be a simple-to-use tool for
      predicting COPD-related hospitalization and mortality.

PMID- 16996901
TI  - The role of patient-centered outcomes in the course of chronic obstructive
      pulmonary disease: how long-term studies contribute to our understanding.
AB  - In chronic obstructive pulmonary disease (COPD), the rate of decline in forced
      expiratory volume in 1 second (FEV1) and progression to disability and death are
      accelerated. COPD management goals include preventing or slowing the progressive
      loss of lung function, relieving symptoms, improving exercise tolerance and the
      patient's health status, preventing and treating exacerbations and complications,
      minimizing side effects of treatment, and reducing mortality. Although lung
      function is important for diagnosis of COPD and classification of its severity,
      clinicians and patients are also very interested in symptoms, ability to
      function, and general well-being (health status). Consequently, increasing
      attention is being given to these patient-centered outcomes. It is possible to
      modify patient-centered outcomes; however, it remains to be seen whether doing so
      can also alter the natural course of the disease and reduce mortality. Two long
      term clinical trials--Towards a Revolution in COPD Health (TORCH) and
      Understanding the Potential Long-Term Impacts on Function with Tiotropium
      (UPLIFT)--will help to answer the question of whether pharmacologic interventions
      are effective in changing the clinical course of COPD. The TORCH study examines
      the long-term effects of combination therapy with an inhaled long-acting beta
      agonist (salmeterol) and a corticosteroid (fluticasone) on reduction of all-cause
      mortality over 3 years. The 4-year UPLIFT study examines the effects of
      maintenance treatment with the once-daily anticholinergic bronchodilator
      tiotropium on the yearly rate of decline in trough FEV1 and the yearly rate of
      decline in FEV1 90 minutes after maximal or near-maximal bronchodilator
      administration. This article examines the rationale for each of these studies and
      provides an overview of study methodology as well as preliminary demographic
      data.

PMID- 16996902
TI  - "Surgical research or comic opera" redux.

PMID- 16996903
TI  - Lung cancer in octogenarians: factors affecting morbidity and mortality after
      pulmonary resection.
AB  - BACKGROUND: Predictors of morbidity and mortality after pulmonary resection for
      lung cancer in patients 80 years of age or older are unknown. METHODS: The
      medical records of all patients 80 years of age or older who had pulmonary
      resection for lung cancer from January 1985 through September 2004 were reviewed.
      RESULTS: There were 379 patients (248 men, 131 women). Median age was 82 years
      (range, 80 to 95 years). Pneumonectomy was performed in 25 patients (6.6%),
      bilobectomy in 7 (1.8%), lobectomy in 240 (63.3%), segmentectomy in 29 (7.7%),
      and wedge excision in 78 (20.6%). The cancer was squamous cell carcinoma in 143
      patients (37.7%), adenocarcinoma in 166 (43.8%), bronchoalveolar cell carcinoma
      in 47 (12.4%), and other in 23 (6.1%). Complications occurred in 182 patients
      (48.0%). These included atrial fibrillation in 75 patients, pneumonia in 27, and
      retained secretions requiring bronchoscopy in 37. Morbidity predictors were male
      sex (odds ratio [OR], 1.6), hemoptysis (OR, 2.3), and previous stroke (OR, 3.8).
      Asymptomatic patients had a significantly decreased probability of complications
      (OR, 0.56). Operative mortality was 6.3% (24 of 379); significant predictors were
      congestive heart failure (OR, 6.0) and prior myocardial infarction (OR, 4.3).
      Factors not associated with mortality included previous myocardial
      revascularization, renal insufficiency (creatinine >1.5 mg/dL), and diabetes
      mellitus. CONCLUSIONS: Pulmonary resection for lung cancer in octogenarians is
      feasible. Congestive heart failure and myocardial infarction, however, correlated
      with a significant increase in mortality. Prior myocardial revascularization,
      renal insufficiency, and diabetes were not associated with increased morbidity
      and mortality.

PMID- 16996904
TI  - Surgical results in T2N0M0 nonsmall cell lung cancer patients with large tumors 5
      cm or greater in diameter: what regulates outcome?
AB  - BACKGROUND: We assessed the surgical results along with the clinical and
      biological features of nonsmall-cell lung cancer (NSCLC) patients with localized
      large tumors. METHODS: The study population consisted of 86 NSCLC patients who
      underwent complete resection of tumors 5 cm or larger in diameter in stage IB
      (T2N0M0). We immunohistochemically assessed the expression of angiostatin and
      endostatin. RESULTS: The median tumor size was 6.0 cm (range, 5 to 14 cm). The
      operative procedures used were lobectomy in 71 cases, bilobectomy in 8 cases, and
      pneumonectomy in 11 cases. Fifty patients (58.1%) relapsed during the mean follow
      up period of 33.6 +/- 4.5 months. The median disease-free interval was 9 months.
      Of 44 recurrent patients whose disease-free interval could be identified, 25
      patients (56.8%) relapsed within 12 months after the operation. The overall 5-
      and 10-year survival rates were 42.0% and 24.2%, respectively. Multivariate
      analysis showed that the degree of pleural involvement and angiostatin expression
      within the tumor were independent prognostic indicators. The endostatin
      expression within tumors also had a weaker relationship with outcome.
      CONCLUSIONS: Long-term surgical results were poor and early relapse was common in
      this cohort. In addition to pleural involvement, the tumor-induced expression of
      angiostatin and endostatin merit further investigation to gain possible insights
      into selection of patients who will benefit from surgery as the first line
      treatment.

PMID- 16996905
TI  - Nine-year single center experience with cervical mediastinoscopy: complications
      and false negative rate.
AB  - BACKGROUND: Mediastinoscopy is a valuable tool for evaluating mediastinal
      pathology and is essential for establishing treatment strategies in most patients
      with lung cancer. We sought to determine the complication and false negative rate
      for mediastinoscopy in an institution that routinely performs this procedure.
      METHODS: We performed a retrospective review of 2,145 consecutive
      mediastinoscopies at a single institution between April 1996 and April 2005.
      Demographics and complications were analyzed. In patients with lung cancer who
      underwent subsequent resection, the false negative rate was calculated. RESULTS:
      Mean patient age was 61 +/- 0.4 years, and 58% (n = 1,253) were male. Pathology
      included lung cancer (n = 1,459), metastatic disease (n = 78), lymphoma (n = 51),
      and other benign disease (n = 557). Twenty-three patients (1.07%) experienced
      complications including hemorrhage (n = 7, 0.33%), vocal cord dysfunction (n =
      12, 0.55%), tracheal injury (n = 2, 0.09%), and pneumothorax (n = 2, 0.09%).
      There was 1 death (0.05%) after pulmonary artery injury. Five of the 7 vascular
      injuries occurred during biopsy of level 4R. Three hundred and forty-three
      patients (23.5%) with lung cancer had positive mediastinoscopies. The false
      negative rate was 56 of 1,019 (5.5%) among lung cancer patients undergoing
      resection. Thirty-two (57%) of the false negatives were due to metastatic disease
      in lymph nodes not normally biopsied during cervical mediastinoscopy (levels 5,
      6, 8, or 9). CONCLUSIONS: Although invasive, mediastinoscopy identified locally
      advanced disease in a significant percentage of this lung cancer population and
      was associated with a low false negative rate. Complications after
      mediastinoscopy were uncommon. These results support the continued routine use of
      mediastinoscopy.

PMID- 16996906
TI  - Clinical experience with radiotracer-guided thoracoscopic biopsy of small,
      indeterminate lung nodules.
AB  - BACKGROUND: Although computed tomography lung-screening programs report a 31% to
      51% incidence of subcentimeter pulmonary nodules, 85% are too small to biopsy or
      interrogate with positron emission spectroscopy scans. We developed a technique
      using transthoracic percutaneous radiotracer injection with thoracoscopic
      radioprobe localization and excision for small pulmonary nodules. This report
      describes our series of the first 46 patients evaluated with this technique.
      METHODS: Forty-six patients (79% smokers; 52% males; median age, 64 years) were
      evaluated. Patient selection was based on the surgeon's anticipated difficulty in
      thoracoscopically locating small nodules because of lesion size or location.
      Computed tomographic-guided injection of radiotracer solution was made into or
      adjacent to the nodule the day of surgery. Intraoperative gamma probe
      localization, followed by thoracoscopic excision of the lesion, was subsequently
      performed. RESULTS: Median nodule size was 9 mm (range, 3 to 22 mm), and median
      depth was 5 mm (range, 0 to 50 mm). Forty-four (96%) of the lesions were
      successfully localized and excised. Median time from injection to surgery was 270
      minutes. Failures were the result of inadvertent pleural or chest wall
      radiotracer placement. Forty-six percent (21 of 46) of the lesions were
      malignant, of which 71% (15 of 21) were primary lung cancers. Patients with lung
      cancer underwent lobectomy or segmentectomy. Fourteen of 15 were stage IA,
      whereas 1 was stage IIIB (6 mm primary with 4 mm intralobar metastasis).
      Complications were three pneumothoraces at the time of radiotracer injection.
      CONCLUSIONS: Computed tomography-guided radiotracer localization of small
      pulmonary nodules combined with thoracoscopic excisional biopsy is feasible and
      safe. This technique successfully localized and excised the nodule in 96% of
      cases.

PMID- 16996908
TI  - Invited commentary.

PMID- 16996907
TI  - Combined analysis of cyclooxygenase-2 expression with p53 and Ki-67 in nonsmall
      cell lung cancer.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is known to play a role in carcinogenesis
      and tumor progression. The aim of this study was to evaluate the relationship
      between COX-2 expression and clinicopathologic features, and to define the
      importance of COX-2 expression alone and in combination with p53 and Ki-67
      expression in the clinical outcome of NSCLC. METHODS: A total of 219 patients
      with stage I-IIIB nonsmall cell lung cancer (NSCLC) who previously underwent
      surgery were analyzed in this study. The COX-2 expression was evaluated by means
      of immunohistochemistry; p53 and Ki-67 immunoreactivity were also studied.
      RESULTS: The COX-2 expression was observed in 137 patients (63%) and was
      significantly associated with lymph node metastasis and the histological grade of
      those with adenocarcinoma (p = 0.02 and 0.04, respectively). Kaplan-Meier
      analyses revealed that COX-2 expression was correlated with poor survival (p =
      0.005), whereas multivariate survival analysis did not reveal COX-2 expression to
      be an independent prognostic factor. When the patients were stratified according
      to gender, age, tumor histology, and disease stage, COX-2 expression was
      significantly associated with unfavorable prognosis in males, younger patients (<
      or = 65 years), and those with adenocarcinoma and stage I tumors. The prognosis
      of patients with tumors negative for both COX-2 and p53 expression was
      significantly favorable, whereas those with tumors positive for COX-2 expression
      and with a high Ki-67 labeling index had a significantly unfavorable prognosis.
      CONCLUSIONS: These findings indicate that combined immunohistochemical analysis
      of COX-2 with p53 and Ki-67 can be useful for identifying the prognosis of NSCLC
      patients.

PMID- 16996909
TI  - Resting energy expenditure and metabolic changes after lung volume reduction
      surgery for emphysema.
AB  - BACKGROUND: Oxygen consumption volume (VO2) and resting energy expenditure are
      increased in emphysema because of impaired respiratory function and mechanics,
      with greater oxygen cost of breathing and altered metabolism. We hypothesized
      that lung volume reduction surgery may improve energy expenditure and metabolism.
      METHODS: In this 1-year prospective study, 30 patients with moderate-to-severe
      emphysema underwent bilateral lung volume reduction surgery; 28 similar patients,
      who refused operation, followed a standard respiratory rehabilitation program.
      Oxygen consumption volume and resting energy expenditure, both corrected for fat
      free mass, VO2 proportion of respiratory muscles (%VO2Resp), respiratory
      quotient, and energy substrate oxidation were determined by using a calorimetric
      chamber with indirect methods. RESULTS: Only after surgery significant
      improvements resulted in 1-second forced expiratory volume (+20.4%, p = 0.009),
      residual volume (-24.8%, p = 0.001), diffusion-lung carbon-monoxide (+18.4%, p =
      0.008), body mass index (+5.5%, p = 0.01), resting energy expenditure (-8.2%, p =
      0.006), and %VO2Resp (-44.1%, p = 0.0008) with increase in respiratory quotient
      (0.79 versus 0.84, p = 0.03) and conversion from prevalent lipid (44.6% versus
      34.3%, p = 0.0007) to prevalent carbohydrate (25.2% versus 42.2%, p = 0.0006)
      metabolism. Thirteen operated on patients discontinued oral steroids, showing the
      most significant improvements. The remaining 17 experienced significant changes
      compared with the rehabilitation group despite oral steroids (resting energy
      expenditure -7.0% versus +4.1%, and %VO2Resp -34.0% versus +0.7%, p = 0.001).
      Decrease of resting energy expenditure and %VO2Resp correlated with reduction of
      residual volume (p = 0.02 and p = 0.001) and increment of body mass index (p =
      0.03 and p = 0.004). CONCLUSIONS: Lung volume reduction surgery significantly
      decreased %VO2Resp and resting energy expenditure over respiratory rehabilitation
      and despite oral steroid therapy. Substrate oxidation changed from prevalent
      lipid to prevalent carbohydrate. Correlations with residual volume and
      nutritional status suggest that restoration of respiratory mechanics reduces
      energy expenditure and approximates metabolism to normal.

PMID- 16996910
TI  - Is obliterative bronchiolitis in lung transplantation associated with
      microvascular damage to small airways?
AB  - BACKGROUND: Acute rejection, a vascular-based disorder, has been identified as
      the major risk factor for obliterative bronchiolitis (OB), an airway-based
      pathology. This study investigated the hypothesis that changes to the
      microvascular blood supply of small airways were associated with the development
      of OB, thus providing a possible link between an acute vascular insult (acute
      rejection) and chronic airway changes (OB). METHODS: Microvasculature of 695
      small airways (99 patients) was assessed in post-mortem lung allograft specimens
      using monoclonal antibodies for von Willebrand factor and CD31. Group A consisted
      of 343 small airways from 58 patients with no evidence of OB. The remaining 41
      patients had histological evidence of OB in some of their small airways and
      grouped as B, C, and D with some patients contributing to all three groups ie,
      their lung specimen had some small airways which were completely obliterated with
      OB, some airways which were partially obliterated and some small airways without
      any histological evidence of OB development. Thus group B consisted of 145 small
      airways (34 patients) without OB. Group C consisted of 171 small airways with
      partial luminal obstruction (36 patients). Group D consisted of 36 small airways
      (14 patients) with complete luminal obliteration. RESULTS: Airway circumference
      (mean +/- standard deviation) was 2.36 +/- 0.37, 2.41 +/- 0.51, 2.49 +/- 0.51,
      and 2.57 +/- 0.79 mm, respectively (p = 0.40). Mean number of blood vessels per
      unit length of airway circumference was 4.12 +/- 1.1, 1.58 +/- 0.61, 2.42 +/-
      1.06, and 4.42 +/- 1.46 vessels/mm, respectively (p < 0.001). Blood vessels with
      circumference greater than 0.2 mm were present in 100%, 64%, 39%, and 7% of small
      airways, respectively (p < 0.001). Univariate and multivariate analyses (donor
      and recipient age, sex, and cytomegalovirus status, recipient pretransplant
      diagnosis, ischemic times, acute rejection and infective episodes, postoperative
      survival days, recipient group [A to D], blood vessels per unit length, and
      airway circumference) confirmed that reduction in blood vessels per unit length
      was associated with the development of OB and was time-independent. CONCLUSIONS:
      Obliterative bronchiolitis was preceded by a decrease in microvascular supply to
      the small airways (group B). The subsequent onset of airway scarring (groups C
      and D) was associated with an increased number of significantly smaller vessels,
      suggestive of neovascularization.

PMID- 16996911
TI  - Ex-vivo perfusion and ventilation of rat lungs from non-heart-beating donors
      before transplant.
AB  - BACKGROUND: We developed an ex-vivo circuit to evaluate human lungs retrieved
      from non-heart-beating donors. We assessed the effect of a similar circuit on the
      function of transplanted rat lungs retrieved from non-heart-beating donors.
      METHODS: One hour after death, Sprague-Dawley rat heart-lung blocks were flushed
      with 20 mL of cold Perfadex, stored cold for 1 hour, then warmed to 37 degrees C
      in a circuit perfused with Earle's crystalloid solution with or without washed
      porcine erythrocytes (hematocrit 12% to 15%). At 37 degrees C, lungs were
      ventilated for 15 minutes with alveolar gas, perfusion-cooled to 20 degrees C,
      flushed again with cold Perfadex, and then stored cold for 2.5 hours. The left
      lung was transplanted using a modified cuff technique with flow probes on the
      main and left pulmonary arteries. After 1 hour of reperfusion, arterial blood
      gases from the left pulmonary vein and wet/dry weight ratio (W/D) of both donor
      lungs were determined. Lungs transplanted after retrieval from heart-beating or
      non-heart-beating donors served as controls (n = 6 per group). RESULTS: Lungs
      gained weight in the circuit but W/D and PO2 were similar after transplantation
      for all groups. After transplantation, vascular resistance was higher and dynamic
      compliance was lower for lungs perfused in the circuit. Myeloperoxidase and
      conjugated diene levels were modestly elevated in lungs transplanted from non
      heart-beating donors irrespective of perfusion in the circuit. CONCLUSIONS: Rat
      lungs are suitable for transplant after ex-vivo perfusion and ventilation. This
      model closely mimics methods used to evaluate the function of lungs retrieved
      from human non-heart-beating donors and can economically evaluate ex-vivo
      therapies for lungs retrieved from non-heart-beating donors.

PMID- 16996912
TI  - Role of airway epithelial injury in murine orthotopic tracheal allograft
      rejection.
AB  - BACKGROUND: Murine tracheal transplantation is a model used to study
      bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after
      lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic
      transplantation does not cause luminal obliteration despite major
      histocompatibility antigen mismatch. Repopulation of the tracheal allografts with
      recipient-derived epithelium confers protection against luminal obliteration. The
      purpose of this study was to determine whether (1) orthotopic tracheal
      transplantation showed signs of allograft rejection, and (2) airway epithelial
      cell injury promoted orthotopic tracheal allograft rejection. METHODS: Forty
      isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic
      tracheal transplants were performed. Damage to airway epithelial cells was
      induced by Sendai viral (SdV) infection and tracheal transplantation into non
      reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice.
      Percent fibrosis and lamina propria to cartilage ratio were calculated with
      computer assistance on harvested allografts. RESULTS: Allografts showed
      significantly more intramural fibrosis compared with isografts at 30, 60, and 180
      days after transplant without luminal occlusion. Tracheal allografts infected
      with SdV showed an increase in fibrosis and lamina propria to cartilage ratio
      compared with noninfected controls. Allografts retrieved from MMP7-KO recipients
      also showed a significant increase in fibrosis and lamina propria to cartilage
      ratio. CONCLUSIONS: Although orthotopic tracheal transplantation does not cause
      luminal obliteration, it results in increased fibrosis in allografts. Damage to
      the respiratory epithelium by viral infection or defective reepithelialization
      after transplant as seen in MMP7-KO recipient mice leads to changes consistent
      with chronic allograft rejection, suggesting a role for epithelial injury in
      bronchiolitis obliterans syndrome development.

PMID- 16996913
TI  - Pleuropneumonectomy for the treatment of Masaoka stage IVA thymoma.
AB  - BACKGROUND: The treatment of locally advanced Masaoka stage IVA thymoma is not
      standardized and is problematic. METHODS: A single-institution retrospective
      study was made of 5 patients with World Health Organization B3 thymomas who
      underwent pleuropneumonectomy for locally advanced thymoma. Two patients had
      recurrent thymoma and 3 presented de novo with stage IVA disease. Patients had a
      variety of induction and adjuvant treatments. RESULTS: There was no operative
      mortality, and only 1 patient had a major complication. Several patients had
      relatively prolonged disease-free survival. The median survival was 86 months,
      and the Kaplan-Meier survival was 75% (95% confidence interval: 53% to 97%) at 5
      years and 50% (95% confidence interval: 25% to 75%) at 10 years. CONCLUSIONS:
      Pleuropneumonectomy can be performed safely in patients with advanced thymomas
      and may improve survival. Highly selected patients might be cured with this
      approach if a complete resection is performed. While the optimal multimodality
      strategy for these patients is unknown, induction chemotherapy followed by
      resection then chemoradiotherapy seems promising.

PMID- 16996914
TI  - Endoscopic retrograde dilation of completely occlusive esophageal strictures.
AB  - BACKGROUND: Completely occlusive esophageal strictures may develop after head and
      neck radiotherapy or esophagectomy with gastric or colonic interposition. Major
      surgical intervention may be required to restore alimentary tract patency when
      endoscopic lumen reconstitution is not feasible by routine antegrade endoscopy.
      Retrograde endoscopic lumen identification and dilation is a useful method to
      reestablish alimentary tract patency, thereby avoiding surgical intervention.
      METHODS: Patients requiring endoscopic dilation for completely occlusive
      esophageal strictures were identified by the gastroenterology, thoracic, and head
      and neck services. Retrograde access was obtained by balloon dilation of either a
      jejunostomy or gastrostomy tract, and an endoscope was passed to the area of
      stricture. Antegrade and retrograde endoscopy were performed simultaneously. A
      guidewire was passed either retrograde or antegrade under direct endoscopic
      visualization, followed by antegrade Savary dilation under fluoroscopic guidance.
      RESULTS: From 2003 to 2006, 9 patients were identified with completely occlusive
      esophageal strictures requiring retrograde lumen identification and dilation.
      Stricture developed in 6 patients after radiotherapy for head and neck cancer and
      in 3 after esophagectomy with either gastric or colonic interposition for
      esophageal cancer. Endoscopic dilation was successful in all patients, without
      perforation. CONCLUSIONS: Retrograde endoscopic lumen identification and dilation
      is an option to reestablish lumen patency of completely occlusive esophageal
      strictures after esophagectomy with gastric or colonic interposition or after
      head and neck chemoradiotherapy.

PMID- 16996915
TI  - Invited commentary.

PMID- 16996916
TI  - Improving results of the Fontan procedure in patients with heterotaxy syndrome.
AB  - BACKGROUND: The Fontan operation in patients with heterotaxy syndrome has been
      associated with a poor prognosis. We studied whether the outcome of those
      patients with heterotaxy syndrome improved compared with those who did not have
      the syndrome after an extracardiac Fontan operation. METHODS: A retrospective
      review was performed on 185 patients who had undergone an extracardiac Fontan
      operation between 1996 and 2005. RESULTS: Sixty-two of the patients had
      heterotaxy syndrome (33.5%). Forty-one had right isomerism and 21 had left
      isomerism. Heterotaxy syndrome was commonly associated with a morphologic right
      ventricle (59.7%), a common atrioventricular valve (72.6%), an interrupted
      inferior vena cava (25.8%), a separate hepatic vein (30.6%), and extracardiac
      pulmonary venous drainage (16.1%). The hospital mortality rate was higher in the
      heterotaxy syndrome than nonheterotaxy (4.8% vs 2.4%; p = 0.05). Eight-year
      survivals were 91.9 +/- 3.2% in the nonheterotaxy group and 89.3 +/- 4.2 % in the
      heterotaxy group (p = 0.39). At 8 years, freedom from reoperation was 90.2 +/-
      3.2% in the nonheterotaxy group and 78.5 +/- 6.2% in the heterotaxy group (p =
      0.15). The outcomes (other than those of arrhythmia) were no different between
      the two groups. The incidences of early and late postoperative arrhythmia were
      29.0% and 25.4%, respectively, in heterotaxy patients, and 15.4% and 10.8% in
      nonheterotaxy patients (p < 0.05). Bradyarrhythmia was found to be more common.
      During follow-up, atrioventricular valve regurgitation of more than mild was more
      common in heterotaxy patients (33.9% vs 18.9%; p = 0.05). CONCLUSIONS: Midterm
      outcomes after an extracardiac Fontan operation in heterotaxy and nonheterotaxy
      patients are similar, except arrhythmia and atrioventricular valve regurgitation.

PMID- 16996917
TI  - Birth weight and complexity are significant factors for the management of
      hypoplastic left heart syndrome.
AB  - BACKGROUND: Classic options for treatment of hypoplastic left heart syndrome
      include the Norwood procedure (NW) and heart transplantation (HT). Recently off
      pump palliative procedures were introduced in the management of these patients.
      Risk factors influencing the decision between the NW with staged reconstruction
      or off-pump palliation and HT were assessed. METHODS: Between January 2002 and
      January 2006, 69 patients with hypoplastic left heart syndrome were referred for
      either a NW (n = 33) or HT (n = 36). Patients referred for HT underwent off-pump
      palliation (catheter-based, n = 20, or surgical hybrid procedures, n = 7) until a
      donor organ became available: including patent ductus arteriosus stenting
      (80.6%), atrial septostomy (41.7%), and branch pulmonary artery banding (55.6%).
      RESULTS: Heart transplantation patients were more complex, based on a higher
      Aristotle Comprehensive Complexity score calculated at birth (HT 18.8 +/- 2.4
      versus NW 17.7 +/- 1.7; p < 0.05). Presurgical death was significantly greater
      for HT referrals (HT 27.8% versus NW 3.0%; p < 0.01); however, there was no
      difference between the two groups in operative (HT 11.5% versus NW 21.9%; not
      significant) or overall mortality (HT 36.1% versus NW 24.2%; not significant). No
      independent risk factors for death were identified with HT; however, a lower
      birth weight (<2.5 kg) and a higher Aristotle score (>20) correlated with
      surgical death with NW (p < 0.01). Noticeably, surgical survival was 85.7% for
      infants with birth weight of 2.5 kg or greater undergoing NW. CONCLUSIONS:
      Overall survival is similar for hypoplastic left heart syndrome patients referred
      for the NW or HT. Lower birth weight and higher complexity are risk factors for
      patients undergoing NW. Off-pump palliation followed by HT or further staged
      palliation should be considered for these high-risk hypoplastic left heart
      syndrome patients.

PMID- 16996918
TI  - Early cavopulmonary anastomosis after Norwood procedure results in excellent
      Fontan outcome.
AB  - BACKGROUND: Children with univentricular hearts and aortic arch obstruction are
      treated sequentially with Norwood procedure, superior cavopulmonary anastomosis
      (SCPA), and Fontan operation. Early SCPA results in lower initial O2 saturation
      and longer hospitalization, but not increased mortality. We sought to determine
      the impact of early SCPA on Fontan candidacy and outcomes. METHODS: Eighty-five
      consecutive patients undergoing Norwood operation between January 1998 and
      February 2003 were divided into group 1 (SCPA at less than 4 months, n = 33) and
      group 2 (SCPA at more than 4 months, n = 52). Of the original cohort, 69 have
      undergone Fontan operation, 7 await Fontan, 1 was transplanted, 3 are not Fontan
      candidates, and 5 died late after SCPA. Group 1 (n = 25) and group 2 (n = 44)
      patients who have completed Fontan operation were compared for preoperative and
      perioperative variables: age, size, O2 saturation, pulmonary artery pressure and
      size, prevalence of tricuspid regurgitation and ventricular dysfunction,
      extubation rate in operating room, duration of pleural drainage, hospital stay,
      and discharge O2 saturation. Late functional status and ventricular function were
      also compared. Survival was compared for original groups 1 and 2. RESULTS: There
      were no differences for any preoperative or perioperative variable, or late
      functional assessment. Actuarial survival at 6 years was also not different (88%
      +/- 5% for group 1 and 94% +/- 4% for group 2, p = 0.72). CONCLUSIONS: Although
      initially more cyanotic and hospitalized longer than older peers, younger SCPA
      patients achieve clinical equivalence by the time of Fontan operation and
      afterward. We conclude that both short- and long-term outcomes support
      performance of early SCPA.

PMID- 16996919
TI  - Impaired power output and cardiac index with hypoplastic left heart syndrome: a
      magnetic resonance imaging study.
AB  - BACKGROUND: Unfavorable cardiac mechanics in children with hypoplastic left heart
      syndrome (HLHS) when compared with other single-ventricle defects may affect long
      term morbidity and outcome. Using noninvasive phase contrast magnetic resonance
      imaging (PC MRI), we examined cardiac mechanics in children with HLHS and
      compared the results to other single-ventricle defects. METHODS: Eighteen
      children with HLHS and 18 children with other single-ventricle defects were
      studied after the Fontan operation. Phase contrast MRI scans were obtained
      perpendicular to the ascending aorta, and flow was quantified using an in-house
      segmentation and reconstruction scheme. The total power output was determined
      using the modified Bernoulli equation along with cardiac output and systemic
      vascular resistance index. RESULTS: Compared with non-HLHS congenital heart
      defects, children with HLHS had significantly lower power output (1.40 +/- 0.39
      versus 1.78 +/- 0.38 W/m2, p < 0.004) and cardiac index (3.15 +/- 0.97 versus
      4.09 +/- 1.23 L x Min(-1) x m(-2), p < 0.009) with a concomitant higher systemic
      vascular resistance index (28.94 +/- 11.5 versus 22.7 +/- 8.53 WU, p < 0.03)
      despite generating similar systolic blood pressures (112.9 +/- 22.4 versus 115.2
      +/- 23 mm Hg, p > 0.05). CONCLUSIONS: Minimally invasive measurements with PC MRI
      in children with HLHS showed significantly lower power output and cardiac index
      when compared with other single-ventricle physiologies. Abnormal aortic flow
      patterns may contribute to power loss and may have long-term survival and
      morbidity implications associated with the Fontan procedure. Elevated systemic
      vascular resistance index despite similar blood pressure opens avenues for
      therapeutic intervention for afterload reduction.

PMID- 16996920
TI  - Complex neonatal single ventricle palliation using antegrade cerebral perfusion.
AB  - BACKGROUND: The efficacy of antegrade cerebral perfusion (ACP) during complex
      neonatal single ventricle palliation requiring arch reconstruction is uncertain.
      We adapted the use of ACP in early 2001 in a programmatic effort to minimize the
      use of deep hypothermic circulatory arrest (DHCA). METHODS: We retrospectively
      analyzed data of 126 consecutive patients operated on between 1995 and 2004,
      including stage-one palliation of hypoplastic left heart syndrome, stage-one
      palliation for nonhypoplastic left heart syndrome, and Damus-Kaye-Stansel
      procedures. Patients were divided into two groups: those repaired with prolonged
      DHCA only (n = 67) and those with ACP (n = 59) and usually a shorter period of
      DHCA. Risk was further stratified into high risk (weight < or = 2.5 kg or other
      cardiac lesion) and usual risk for each group. RESULTS: Survival at 30 days in
      the usual-risk groups was 72.0% DHCA and 93.2% ACP (p < or = 0.025), and in the
      high-risk groups it was 61.5% DHCA and 80% ACP (not significant). One-year
      survival in the usual-risk groups was 57.4% DHCA and 84.1% ACP (p < or = 0.01),
      and in the high-risk groups it was 38.5% DHCA and 46.7% ACP (not significant).
      Overall survival to date is 52.2% DHCA and 71.2% ACP (p < or = 0.5). CONCLUSIONS:
      There is a statistically significant survival advantage for usual-risk patients
      with the use of ACP. Although there is a trend to improved survival in the high
      risk groups, it does not reach statistical significance and long-term outcomes in
      these patients remains disappointing. We continue to use ACP and believe it
      contributes to an overall survival advantage in our institution.

PMID- 16996921
TI  - Complete repair of conotruncal defects with an interatrial communication:
      oxygenation, hemodynamic status, and early outcome.
AB  - BACKGROUND: Complete repair of conotruncal defects frequently uses maintenance of
      an interatrial communication. Postoperative right ventricular dysfunction may be
      characterized by elevated right atrial pressure and decreased systemic oxygen
      saturation owing to right-to-left shunting at the atrial level. METHODS: From
      January 1996 to December 2005, 112 patients younger than 6 months of age
      underwent complete repair of tetralogy of Fallot or truncus arteriosus. An
      interatrial communication was used in 80 of 112 patients (71%). Hemodynamic data
      were determined during the first 48 hours after surgery. RESULTS: In patients
      with an atrial communication, mean oxygen saturation reached a nadir of 94% +/-
      6%, and mean arterial PO2 a nadir of 73 +/- 25 mm Hg at 16 to 24 hours after
      surgery; both increased during the second 24 hours. At hospital discharge, median
      oxygen saturation was 98% (range, 86% to 100%). During the first 48 hours, mean
      oxygen saturation was less than 90% in 13 patients; the only multivariate risk
      factor was younger patient age. Mean right atrial pressure was greater than 10 mm
      Hg in 30 patients; multivariate risk factors were older patient age and repair
      with a transannular patch. CONCLUSIONS: After complete repair of conotruncal
      defects using an interatrial communication, systemic oxygenation reaches a nadir
      at 24 hours after surgery, and improves by the time of hospital discharge.
      Clinically significant desaturation occurs in a small minority of patients.
      Infants undergoing repair before 2 months of age are at higher risk for systemic
      desaturation. The effects of an interatrial communication on systemic oxygenation
      should not be considered a contraindication to complete repair in early infancy.

PMID- 16996922
TI  - Short and midterm results of aortic valve cusp extension in the treatment of
      children with congenital aortic valve disease.
AB  - BACKGROUND: We evaluated our experience with aortic valve cusp extension
      techniques to identify predictors of successful intraoperative repair and
      subsequent durability. METHODS: Twenty-two children (ages 5-18 years) underwent
      aortic cusp extension with autologous pericardium between 1999 and 2005. Sixteen
      children had previous surgical or percutaneous intervention. Ten children had
      bicuspid aortic valves. Cusp extensions were performed on 1 cusp in 3 patients, 2
      cusps in 3, and 3 cusps in 16. Serial echocardiographic measures (n = 81) were
      obtained during a 5-year period and underwent blinded review. Longitudinal
      trajectories of ventricular and aortic valve function were modeled using mixed
      linear regression analysis. RESULTS: There was no hospital or late mortality.
      Five-year freedom from valve replacement was 75%. Comparison of preoperative and
      post-repair echocardiograms demonstrated reductions in aortic insufficiency
      (decreased in jet-width/aortic valve diameter ratio from 0.39 +/- 0.12 to 0.22 +/
      0.11; p < 0.0001), aortic stenosis (decreased in peak aortic valve gradient from
      41 +/- 25 mm Hg to 29 +/- 15 mm Hg; p = 0.04), and left ventricular end-diastolic
      dimensions Z-score (decreased from 1.39 +/- 0.38 to 1.16 +/- 0.34; p < 0.001).
      During the follow-up period, post-repair jet-width and aortic valve diameter
      increased nonlinearly (p < 0.001). Patients with postoperative peak aortic
      gradients greater than 30 mm Hg had progression of aortic stenosis, whereas those
      with lesser postoperative peak gradients tended to regress during follow-up (p <
      0.001). The decrement in Z-score of the left ventricular end-diastolic dimensions
      remained stable during the follow-up period. CONCLUSIONS: Aortic valve cusp
      extension can result in acceptable hemodynamic results with stabilization of left
      ventricular geometry. However, residual lesions are common and progression and
      regression of these lesions can be predicted based on echocardiographic data.

PMID- 16996923
TI  - The Ross-Konno procedure in children: outcomes, autograft and allograft function,
      and reoperations.
AB  - BACKGROUND: The Ross aortic valve replacement with a modified Konno-type
      enlargement Ross-Konno procedure of the aortic annulus and subannular region
      allows an autograft aortic valve replacement for children with significant
      annular and subannular hypoplasia. The potential for growth and the proven
      durability of the autograft make the Ross-Konno procedure an ideal aortic valve
      replacement for this subgroup with multilevel left ventricular outflow tract
      obstruction. We reviewed our institutional midterm experience to assess autograft
      and homograft hemodynamics, and management after a Ross-Konno procedure. METHODS:
      Between 1995 and 2005, 14 consecutive children (mean age, 6.4 +/- 5.9 years;
      range, 1 month to 17 years) underwent the Ross-Konno procedure. All children had
      severe to critical aortic stenosis or multilevel left ventricular outflow tract
      obstruction. RESULTS: There was 1 early and 1 late death with a mean follow-up of
      5.7 +/- 3.6 years. Actuarial survival at 10 years was 86%. Three patients
      underwent right ventricular outflow tract reoperation for conduit replacement for
      homograft dysfunction and one patient required redo aortic root replacement with
      a mechanical valves for progressive aortic insufficiency. Freedom from right
      ventricular outflow tract and autograft reoperation at 10 years is 77% and 92%,
      respectively. Aortic annular dilation was not observed in all patients.
      Univariate and multivariate analysis identified no risk factors for autograft or
      homograft valve-related reoperation. CONCLUSIONS: The Ross-Konno procedure is an
      excellent technique to treat complex multilevel left ventricular outflow tract
      obstruction in children with significant annular and subannular hypoplasia. The
      autograft demonstrated durability without development of aortic stenosis or
      progressive dilation and a low incidence of developing progressive aortic
      insufficiency. Enlargement of the aortic annulus appear to parallel somatic
      growth in most instances.

PMID- 16996924
TI  - Invited commentary.

PMID- 16996925
TI  - Bovine jugular vein conduit for right ventricular outflow tract reconstruction:
      evaluation of risk factors for mid-term outcome.
AB  - BACKGROUND: The bovine jugular vein conduit (Contegra [Medtronic, Inc,
      Minneapolis, MN]) is one option for right ventricular outflow tract
      reconstruction. We examined the effect of patient age, conduit size,
      hemodynamics, and cardiac malformation on early and mid-term outcome. METHODS:
      Seventy-eight bovine jugular vein implantations were performed over 5 years.
      Follow-up averaged 31 +/- 17 months. Risk factor and adverse event analyses for
      graft dysfunction were performed by multivariate logistic regression and Kaplan
      Meier analysis. RESULTS: There was no early mortality. Two late deaths occurred
      after 9 and 15 months. Early postoperative echocardiography revealed bovine
      jugular vein regurgitation greater than 2+ in 10 patients, all of which had
      conduit dilatation, had received a 12-mm conduit, and had a right-ventricular-to
      left ventricular pressure ratio greater than 0.6. Two additional patients had
      severe conduit incompetence develop at the 2-year follow-up. During follow-up,
      mean gradients increased from 15 to 23 mm Hg (p = 0.03) and stenosis at the
      distal anastomosis occurred in 25% of patients. Percutaneous interventions were
      performed in 19 patients (24.4%). Conduit exchange was required in 10 patients
      (12.8%) after a mean of 14.9 months for severe graft incompetence (8 patients)
      and progressive supravalvular stenosis (2 patients). Freedom from reoperation was
      77.6% and 59.3% at 1 and 4 years for patients less than 1 year of age compared
      with 93.5% and 87.4% for patients older than 1 year of age (p < 0.001). Risk
      factors for reoperation were age less than 1 year, correction of truncus
      arteriosus, conduit size of 12 mm, and persistently elevated right-ventricular-to
      left ventricular pressure ratio greater than 0.6 (p = 0.001 each). CONCLUSIONS:
      Bovine jugular vein implantation is associated with low reoperation and
      acceptable reintervention rate in patients older than 1 year of age. In infants
      with persistently elevated right ventricular pressure, reoperation rate was high
      and had to be compared with other established surgical options.

PMID- 16996926
TI  - Total transatrial correction of tetralogy of Fallot: no outflow patch technique.
AB  - BACKGROUND: The aim of this study was to analyze the feasibility and early
      results of transatrial total correction of tetralogy of Fallot (TOF). METHODS: Of
      the 860 patients undergoing total correction for TOF between January 2000 and
      July 2005, 334 patients were considered morphologically suitable for transatrial
      total correction. The ventricular septal defect (VSD) closure, infundibular
      resection, and pulmonary valvotomy were performed through the right atrium
      without a right ventriculotomy. Age ranged from 6 months to 40 years (median, 2.8
      years), and weight ranged from 5.5 to 70 kg (median, 14 kg). RESULTS:
      Peroperatively, 34 patients required right ventriculotomy and transannular patch;
      hence, they were excluded from the study. In addition, pulmonary arteriotomy was
      required in 71 patients (22.9%). There were 4 hospital deaths. There were 4 early
      reoperations (residual/additional VSD in 3 and tricuspid regurgitation in 1). Two
      patients had complete heart block requiring permanent pacemaker. Echocardiography
      at discharge showed a peak right ventricular outflow tract gradient of 20 +/- 5.2
      mm Hg. Mean follow-up was 26.8 +/- 4.2 months (range, 1 to 52 months). The right
      ventricular outflow tract gradients reduced to 13 +/- 4.2 mm Hg after a mean
      interval of 18.8 +/- 5.2 months. Follow-up New York Heart Association class was I
      in 240 cases (82%), II in 49 (16%), and III in 7 (2%). There were no late deaths
      or reoperations. CONCLUSIONS: Transatrial total correction of TOF can be
      accomplished in selected patients with good early results. In 300 cases (90%),
      the feasibility of transatrial total correction could be predicted accurately.

PMID- 16996927
TI  - Three-dimensional echo and videocardioscopy-guided atrial septal defect closure.
AB  - BACKGROUND: Current real-time three-dimensional echocardiography systems (RT3DE)
      can provide sufficient visualization to permit atrial septal defect (ASD)
      closure. However, detailed visualization of small objects inside the heart is
      still suboptimal because of limited resolution, which is a limitation for
      clinical application. We evaluate the complementary use of videocardioscopy in
      image-guided ASD closure. METHODS: In a pig model (n = 5), a 4-mm to 8-mm ASD was
      created with RT3DE guidance. Defect closure was accomplished with a catheter
      based patch-delivery system fixed around the defect with mini-anchors under
      combined RT3DE and videocardioscopy guidance. The endoscope was inserted into the
      heart through a custom built port designed to allow visualization in the presence
      of blood. RESULTS: All ASDs were successfully closed. The combination of RT3DE
      and videocardioscopy allowed detailed visualization of intracardiac structures,
      instruments, patch, and mini-anchors. CONCLUSIONS: Beating-heart ASD closure can
      be achieved with combined RT3DE and videocardioscopy imaging. Use of
      videocardioscopy provides high-resolution imaging and likely improves safety of
      the image-guided procedure.

PMID- 16996928
TI  - Combined atrial septal defect surgical closure and irrigated radiofrequency
      ablation in adult patients.
AB  - BACKGROUND: Atrial arrhythmias are relatively common among patients over 40 years
      old with atrial septal defect (ASD) and are a precipitating cause of heart
      failure. Surgical closure of the ASD in these patients is feasible and is
      associated with a low mortality rate and a beneficial effect on the clinical
      status; however the occurrence of atrial arrhythmia does not decrease after
      surgery. We present the results of our preliminary experience with surgical ASD
      closure combined with intraoperative irrigated radiofrequency (IRF) ablation in
      adult patients. METHODS: During a 26-month period between September 2002 and
      December 2004, 15 patients more than 40 years old with ASD and atrial arrhythmia
      underwent elective surgical closure of the defect and intraoperative IRF
      ablation. All patients had supraventricular arrhythmias: 8 had permanent atrial
      fibrillation, whereas 7 had previous episodes of atrial flutter or intra-atrial
      reentry tachycardia. The biatrial approach (Cox-Maze III procedure) was used in 7
      patients and a right-sided Maze procedure (ablation lines on the right atrium
      only) was carried out in the remaining 8 patients. RESULTS: All patients survived
      the procedure. Fourteen patients left the operating room in sinus rhythm and 1
      had a pacemaker implanted. There were no complications resulting from the IRF
      ablation. All 15 patients survived over the average follow-up period of 24
      months. Thirteen patients were still in sinus rhythm, 1 had pacemaker rhythm, and
      only 1 (1 of 15; 6.5%) suffered a recurrence of atrial fibrillation 3 months
      after the procedure. CONCLUSIONS: We suggest adding intraoperative IRF ablation
      during surgical closure of an ASD in all adult ASD patients with arrhythmias. The
      IRF ablation is easy to perform, safe, and effective.

PMID- 16996929
TI  - Risk-stratified evaluation of amiodarone to prevent atrial fibrillation after
      cardiac surgery.
AB  - BACKGROUND: Amiodarone prophylaxis (AMP) reduces the prevalence of postoperative
      atrial fibrillation (POAF) after cardiac surgery. We investigated the impact of
      AMP on the frequency and duration of POAF, the intensive care unit and hospital
      length of stay, and its cost-effectiveness in a risk-stratified cohort. METHODS:
      A retrospective, observational analysis of 509 patients who underwent cardiac
      surgery in 2003 was performed. Data sources included The Society of Thoracic
      Surgeons national database; medical and medication administration records; and
      the activity-based cost data from our institution. Risk stratification for POAF
      was determined using a validated risk index. Cost-effectiveness was determined
      from the hospital's perspective. RESULTS: The mean patient age was 63 years, 27%
      were female, 80% underwent coronary artery bypass grafting, and 29% underwent
      valve surgery. When a risk-stratified evaluation was made, 50% of patients were
      at an elevated risk for having POAF develop. When compared with nonprophylaxed
      patients, those receiving AMP (59%) experienced less POAF (31% vs 22%; p = 0.027)
      and shorter durations of POAF (4.7 vs 2.7 days; p = 0.025). In the elevated-risk
      group, AMP clinically (but not significantly) reduced length of stay in the
      intensive care unit (101 vs 68 hours; p > 0.05) and post-procedural hospital
      length of stay (9.7 vs. 7.9 days, p > 0.05). In the elevated-risk group, AMP was
      robustly cost-effective in reducing POAF. CONCLUSIONS: Amiodarone prophylaxis
      reduced the prevalence and duration of POAF. Baseline risk for POAF was a major
      determinant of the overall cost-effectiveness of AMP. The greatest cost savings
      with AMP was seen in patients at an elevated risk for POAF. These findings
      suggest the need for risk stratification when prescribing AMP.

PMID- 16996930
TI  - Long-term recovery of exercise ability after pulmonary endarterectomy for chronic
      thromboembolic pulmonary hypertension.
AB  - BACKGROUND: The exercise capacity of patients with thromboembolic pulmonary
      hypertension was investigated to clarify the long-term effects of pulmonary
      endarterectomy. This capacity was assessed by measuring cardiopulmonary factors
      during cardiopulmonary exercise testing at the maximal level of exercise and a 6
      minute walk test at the submaximal level. Their survival rate was also
      determined. METHODS: We conducted a retrospective review of the clinical records
      of 102 patients who underwent pulmonary endarterectomy (63 women; median age, 53
      years). RESULTS: Eight (7.8%) hospital mortalities were encountered. Three late
      mortalities due to fulminant hepatitis, breast cancer, and pneumonia in a patient
      under steroid therapy were unrelated to pulmonary endarterectomy. The actual
      survival rate including hospital mortalities was 90.9% at 3 years and 84.0% at 5
      years. All hemodynamic measurements significantly improved and reached a plateau
      1-month after endarterectomy. The cardiopulmonary exercise test at the maximal
      exercise level revealed that peak oxygen uptake (V(O2)) baseline was 13.8 +/- 3.2
      mL/min/kg, and at 1-month was 16.2 +/- 4.2 mL/min/kg (p = 0.0015) and ventilatory
      response to carbon dioxide production (V(E)-V(CO2)) slope baseline was 46.5 +/-
      8.4 mL/min/kg, and at 1-month was 39.9 +/- 7.4 (p = 0.0006), which gradually and
      significantly improved during the first year after endarterectomy (peak V(O2),
      19.9 +/- 3.9 mL/min/kg [p < 0.0001] and V(E)-V(CO2) slope, 33.2 +/- 5.4 mL/min/kg
      [p <0.0001]). The 6-minute walk test, which reflects the systemic response at the
      submaximal level of functional capacity, showed that the walking distance
      gradually and significantly increased for up to 1 year after endarterectomy
      (baseline, 358 +/- 102 meters [m]; at 1-month, 433 +/- 105 m; and at 1-year, 490
      +/- 80 m [p < 0.0001]) and then reached a plateau. CONCLUSIONS: After pulmonary
      endarterectomy, the hemodynamic recovery occurred immediately, and the patients'
      exercise capacity improved during the year. The 6-minute walk test was a good
      indicator to assess the recovery of exercise capacity.

PMID- 16996931
TI  - Septal anterior ventricular exclusion procedure for idiopathic dilated
      cardiomyopathy.
AB  - BACKGROUND: Eight-year experience with the septal anterior ventricular exclusion
      procedure for congestive heart failure due to idiopathic dilated cardiomyopathy
      was evaluated. METHODS: In 36 patients (27 men and 9 women with a mean age of 60
      years) with heart failure; New York Heart Association class III/IV (21/15); and
      mitral regurgitation 2+ or greater, the procedure was indicated when the
      diastolic dimension was 75 mm or greater, and the septum was akinetic. A long,
      narrow oval patch was sutured to form a downsized elliptical left ventricle by
      excluding the septum and anterior wall. Mitral reconstruction was combined for
      all patients (26 repairs with undersized ring and 10 replacements with
      bioprosthesis) and tricuspid repair was added for 16 patients (44%). RESULTS:
      Hospital mortality was 13.8% (5 of 36), with 6.5% (2 of 31) in elective and 60%
      (3 of 5) in emergency operations. Ejection fraction increased from 20.9% +/- 6.4%
      to 27.5% +/- 8.8%, left ventricular diastolic dimension decreased from 81.9 +/-
      9.2 mm to 70.1 +/- 10.0 mm, and left ventricular endodiastolic and endosystolic
      volume indices decreased from 236.5 +/- 65.0 mL/m2 to 183 +/- 60.5 mL/m2 and from
      181.3 +/- 55.4 mL/m2 to 133.5 +/- 54.1 mL/m2, respectively. Left ventricular
      endodiastolic pressure decreased from 24.3 +/- 9.7 mm Hg to 19.4 +/- 7.6 mm Hg.
      Brain natriuretic peptide decreased from 975 +/- 866 pg/mL to 404 +/- 366 pg/mL
      at 1 to 6 postoperative months. Eleven late deaths were noted and were due to
      heart failure (6), sudden death (4) and stroke (1). The mean New York Heart
      Association class was 1.7 among the survivors. One- and 3-year survival rates
      were 67.5% and 60.7%, respectively. CONCLUSIONS: The septal anterior ventricular
      exclusion procedure with mitral reconstruction is a useful option for the
      treatment of advanced idiopathic dilated cardiomyopathy in extremely dilated left
      ventricle with akinetic septum.

PMID- 16996932
TI  - Left ventricle volume affects the result of mitral valve surgery for idiopathic
      dilated cardiomyopathy to treat congestive heart failure.
AB  - BACKGROUND: Mitral valve surgery is a recommended treatment for congestive heart
      failure; however, its effect for idiopathic dilated cardiomyopathy (DCM) with an
      extremely enlarged left ventricle (LV) is not well documented. We examined our
      long-term results of mitral valve surgery for idiopathic dilated cardiomyopathy.
      METHODS: Fifty-five patients of idiopathic dilated cardiomyopathy have undergone
      mitral valve surgery to treat intractable congestive heart failure since 1998.
      Forty-two patients were male with an average age of 55. Preoperative New York
      Heart Association functional class was III in 25, IV in 30, and 19 were dependent
      on inotropic infusion. The mitral valve was repaired in 37 patients and replaced
      in 18. The tricuspid valve was repaired in 35 patients and replaced in 3. We
      divided 46 elective cases into two groups by LV end-systolic volume index.
      RESULTS: Postoperatively, an intraaortic balloon pump was required in 2 patients
      and a left ventricular assist device in 1; both were emergent cases. Hospital
      mortality was noted 4.3% in elective cases (2 of 46) and 14.5% in overall cases
      (8 of 55). One-year, 3-year, and 5-year survival rate of elective cases was
      73.3%, 58.2%, and 51.7%, respectively. Left ventricle size has decreased and LV
      contractility has increased in a small LV group year by year, but those in a
      large LV volume group have not changed subsequently after surgery. There was a
      significant difference noted in the survival rate of the two groups divided by LV
      end-systolic volume index. CONCLUSIONS: Mitral valve surgery for idiopathic
      dilated cardiomyopathy to treat end-stage heart failure is relatively safe and
      effective in elective status. However, isolated mitral reconstruction without any
      other type of surgery may not suffice for an extremely enlarged LV.

PMID- 16996933
TI  - Edge-to-edge technique for mitral valve repair: medium-term results with
      echocardiographic follow-up.
AB  - BACKGROUND: The follow-up data for the Alfieri edge-to-edge technique of mitral
      valve repair is still a matter of interest. We describe the medium-term results
      of a single surgeon's practice with clinical and echocardiographic follow-up.
      METHODS: Between October 1998 and July 2003, 41 patients underwent the Alfieri
      repair. Mean age of the patients was 68 years, 34.2% were female, 26 (63.41%) had
      New York Heart Association (NHYA) class III symptoms, and 19 (46.3%) had
      concomitant coronary disease. Preoperatively, 26 patients had grade 4+, 12
      patients had grade 3+, and 3 patients had grade 2+ mitral regurgitation. The
      pathologies included myxomatous degeneration (73.2%), ischemic cardiomyopathy
      (12.2%), rheumatic (4.9%), dilated cardiomyopathy (2.4%), previous infection
      (2.4%), and indeterminate pathology (4.9%). Thirty-three patients (80.4%) had a
      ring annuloplasty, and 17 (41.4%) had concomitant coronary surgery. Median
      duration of echocardiographic follow-up was 22.1 months (range, 0.2 to 60.1).
      RESULTS: Hospital mortality was 4.8% (2 of 41). Four patients underwent
      reintervention on the mitral valve. At follow-up, 26 patients (66.6%) were in
      NYHA class I. The actuarial freedom from death or reoperation at 5 years was
      80.4%. Transthoracic echocardiography was performed in 94.3% of the 35 hospital
      survivors who did not undergo reoperation. Twenty-nine patients (87.8%) had grade
      0-1+ mitral regurgitation, and the remainder had grade 2+ mitral regurgitation.
      All patients discharged from hospital were alive in December 2005. CONCLUSIONS:
      The Alfieri edge-to-edge repair for mitral regurgitation is a safe and useful
      technique and should be included in the armamentarium of the mitral valve
      surgeon.

PMID- 16996934
TI  - Effects of annular size, transmitral pressure, and mitral flow rate on the edge
      to-edge repair: an in vitro study.
AB  - BACKGROUND: Although edge-to-edge repair is an established adjunctive procedure,
      there is still debate on its long-term durability and efficacy. METHODS: Fifteen
      porcine mitral valves were studied in a physiologic left heart simulator with a
      variable size annulus (dilated = 8.22 cm2, normal = 6.86 cm2, contracted = 5.5
      cm2). Mitral valves were tested under steady and physiologic pulsatile flow
      conditions (cardiac outputs: 4 to 6 L/min), at peak transmitral pressures between
      100 mm Hg and 140 mm Hg. A miniature force transducer was used to measure the
      Alfieri stitch force (F(A)). Mitral flow rate (MFR), transmitral pressure,
      effective orifice area, mitral regurgitation, and F(A) were monitored. RESULTS:
      The edge-to-edge repair led to a decrease in effective orifice area of 16.55% +/-
      8.22%; further reduction in effective orifice area was attained with annular
      contraction. Mitral regurgitation after the edge-to-edge repair was significantly
      higher (p <0.05) with annular dilation. In the pulsatile experiments, two peaks
      in F(A) were observed: one during systole (F(A) = 0.059 +/- 0.024 N) and a second
      during diastole (F(A) = 0.072 +/- 0.021 N). Multivariate analysis of variance
      analysis showed that during systole, transmitral pressure and mitral annular area
      (MAA) had significant effects on F(A) [F(A) = (4.40 x 10(-4)) transmitral
      pressure (mm Hg) + (5.0 x 10(-3)) MAA (cm2) - 0.05 (R2 = 0.80)], whereas during
      diastole MFR and MAA had significant effects on F(A) [F(A) = (1.03 x 10(-4)) MFR2
      (L/min) - (1.60 x 10(-3)) MAA (cm2) + 0.02 (R2 = 0.90)]. CONCLUSIONS: With
      annular dilation, mitral regurgitation persisted even after the edge-to-edge
      repair. The edge-to-edge repair does not cause clinically relevant mitral valve
      stenosis in a normal size mitral valve. Mitral flow rate and transmitral pressure
      are the main determinants of F(A) during the cardiac cycle. Increasing annular
      area increases F(A) during systole but decreases F(A) during diastole. Systolic
      F(A) may become dominant with increases in MAA or peak transmitral pressure, or
      both.

PMID- 16996935
TI  - In-vivo dynamic deformation of the mitral valve anterior leaflet.
AB  - BACKGROUND: Surgical techniques have been developed for mitral valve repair for a
      wide range of pathologies. However, excessive tissue stress and damage have been
      identified as etiologic factors limiting long-term durability. Before
      computational models to optimize valve repair can be realistically developed, in
      vivo dynamic mitral valve leaflet strain data are required. However, these data
      do not presently exist. In the present study, a sheep model and sonomicrometry
      were used to compute the in-surface Eulerian strain tensor of the anterior
      leaflet over the cardiac cycle at varying afterloads. METHODS: The anterior
      leaflet of nine Dorsett sheep (35 kg to 45 kg) was instrumented with nine 1-mm
      hemispherical piezoelectric transducers in a 15-mm square array. Three
      dimensional crystal spatial positions were recorded at 250 Hz over several
      cardiac cycles, with peak left ventricular pressures varying from 90 mm Hg to 200
      mm Hg. The in-surface Eulerian strain tensor was computed from the crystal
      displacements. RESULTS: The mitral valve anterior leaflet experiences large
      anisotropic strains and peak strain rates of 400%/s, followed by an absolute
      cessation of any deformation during systole. Increasing left ventricular pressure
      also increased the effective leaflet stiffness but not the peak strains.
      CONCLUSIONS: We report the first data on the dynamic in-vivo strain tensor of a
      functioning mitral valve anterior leaflet, which indicated large anisotropic
      strains and very high strain rates. Our observations also suggest that changes in
      left ventricular pressure and annular geometry result in altered effective
      leaflet stiffness, and may be an important factor in reducing leaflet stress and
      as such potentially affect mitral valve repair longevity.

PMID- 16996936
TI  - Invited commentary.

PMID- 16996937
TI  - Root replacement using stentless valves in the small aortic root: a propensity
      score analysis.
AB  - BACKGROUND: Root replacement using a stentless bioprosthesis may be the optimal
      approach to avoid patient-prosthesis mismatch in patients with a small aortic
      root. Primary root replacement, however, is considered to be associated with
      increased surgical risk. We compared early outcome of full root replacement with
      a stentless bioprosthesis with that of aortic valve replacement with a stented
      bioprosthesis using propensity score-matching analysis. METHODS: Of 231 patients
      undergoing elective, first-time aortic valve replacement with a small root (< or
      = 22 mm), 120 patients were selected using propensity score-matching analysis.
      They underwent either root replacement using a 23-mm stentless bioprosthesis
      (stentless group, n = 60) or supra-annular aortic valve replacement using a 21-mm
      stented bioprosthesis (stented group, n = 60). Preoperative characteristics and
      frequency of concomitant operations were identical. RESULTS: Duration of
      operation (196 +/- 54 versus 174 +/- 49 minutes), cardiopulmonary bypass (112 +/-
      36 versus 91 +/- 33 minutes), and aortic cross-clamping (76 +/- 21 versus 61 +/-
      21 minutes) were significantly longer in the stentless group. However, the need
      for perioperative transfusion and the incidence of postoperative reexploration
      for bleeding (3% versus 8%) was lower, and ventilation time was shorter. Mean
      duration of intensive care and hospital stay were also significantly shorter (2.3
      +/- 1.7 versus 4.0 +/- 3.9 days, 8.9 +/- 3.1 versus 12.4 +/- 5.7 days). In
      hospital mortality was identical (5% each). No independent predictor for in
      hospital mortality was identified. CONCLUSIONS: Full root replacement using a
      stentless bioprosthesis does not increase postoperative morbidity or mortality of
      aortic valve replacement and may be advantageous in patients with a small aortic
      root.

PMID- 16996938
TI  - Reoperation of the aortic valve in octogenarians.
AB  - BACKGROUND: Because of increasing life expectancy of patients with heart valve
      replacement and a limited durability of heart valve bioprostheses, cardiac
      reoperation becomes necessary in a significant percentage of patients. Reliable
      data on mortality and risk factors in octogenarians after replacement of aortic
      valve prostheses are scanty, however. METHODS: We retrospectively analyzed 71
      patients aged 80 years and older who underwent cardiac reoperation of the aortic
      valve (69 bioprostheses, 2 mechanical prostheses) between 1991 and 2004 at our
      heart center. Survival rate of the study cohort was compared with a control group
      of octogenarians matched for age, sex, and year of aortic valve replacement. To
      assess predictors of 30-day survival and 3-year survival, we performed univariate
      and multivariate analyses. RESULTS: Survival rates at 30 days, 1 year, 3 years
      and 5 years were 83.6%, 76.1%, 70.8%, and 51.3%, respectively. Results did not
      differ significantly between the study cohort and the controls. Patients with
      reoperation had an estimated median survival of 5.6 years. Postoperative
      complications such as low cardiac output syndrome and intestinal failure were the
      only independent predictors of 30-day survival (p = 0.020 and p = 0.015,
      respectively). Low cardiac output, intestinal failure, and diabetes mellitus were
      independent predictors of 3-year survival (p = 0.001 to 0.033). CONCLUSIONS: Our
      data demonstrate that it is possible to achieve an acceptable outcome in
      octogenarians who have reoperation of the aortic valve prosthesis. Early and mid
      term survival is predominantly influenced by unexpected postoperative
      complications and not by preoperative risk factors, with the exception of
      diabetes mellitus.

PMID- 16996939
TI  - Invited commentary.

PMID- 16996940
TI  - Prognostic implications of preoperative atrial fibrillation in patients
      undergoing aortic valve replacement: is there an argument for concomitant
      arrhythmia surgery?
AB  - BACKGROUND: The prognostic significance of preoperative atrial fibrillation (AF)
      at the time of aortic valve replacement is unknown, as is the potential role for
      concomitant arrhythmia surgery. METHODS: We performed a cohort comparison of
      patients with preoperative AF (n = 129) and preoperative sinus rhythm (SR, n =
      252) undergoing aortic valve surgery between 1993 and 2002; patients were matched
      for age, gender, and left ventricular ejection fraction. Follow-up (mean
      interval, 4.5 years) was 98% complete. Primary endpoints were late cardiac and
      all-cause mortality, as well as major adverse cardiac or cerebrovascular event.
      RESULTS: Patients with preoperative AF presented with more severe congestive
      heart failure (p = 0.03) and more often had significant tricuspid regurgitation
      (p = 0.01) preoperatively. They also had worse late survival (risk ratio [RR] for
      death = 1.5, p = 0.03) with 1-, 5-, and 7-year survival rates substantially
      reduced at 94%, 87%, and 50%, respectively, for those in AF versus 98%, 90%, and
      61% for patients in sinus rhythm preoperatively. Individuals in AF had a greater
      probability of subsequent rhythm-related intervention (RR = 4.7, p = 0.0002), and
      more frequently developed congestive heart failure (25% vs 10%, p = 0.005) and
      stroke (16% vs 5%, p = 0.005). By multivariable analysis, preoperative AF was an
      independent predictor of late adverse cardiac and cerebrovascular events, but not
      late death. CONCLUSIONS: Performance of concomitant arrhythmia surgery in
      patients undergoing aortic valve surgery may reduce late morbidity; however, its
      potential impact on late mortality in this high-risk subset of patients remains
      unclear.

PMID- 16996941
TI  - Familial thoracic aortic aneurysms and dissections--incidence, modes of
      inheritance, and phenotypic patterns.
AB  - BACKGROUND: We examined the genetic nature and phenotypic features of thoracic
      aortic aneurysms (TAAs) and dissections in a large cohort of patients. METHODS:
      Interviews were conducted with 520 patients with TAAs and their pedigrees were
      compiled to identify family members with aneurysms. Study patients were divided
      into three groups: 101 non-Marfan patients, in 88 pedigrees, had a family pattern
      for TAA (familial group), 369 had no family pattern (sporadic group), and 50 had
      Marfan syndrome (MFS). We determined incidence of familial clustering, age at
      presentation, rate of aneurysm growth, incidence of hypertension, correlation of
      aneurysm sites among kindred, and pedigree inheritance patterns. RESULTS: An
      inherited pattern for TAA was present in 21.5% of non-MFS patients. The
      predominant inheritance pattern was autosomal dominant (76.9%), with varying
      degrees of penetrance and expressivity. The familial TAA group was significantly
      younger than the sporadic group (p < 0.0001), but not as young as the MFS group
      (p < 0.0001) (mean ages, 58.2 versus 65.7 versus 27.4 years). Among all 197
      probands and kindred with aneurysm, 131 (66.5%) had TAA, 49 (24.9%) had abdominal
      aortic aneurysm (AAA), and 17 (8.6%) had cerebral or other aneurysms. Ascending
      aneurysm paired most commonly with ascending, and descending with abdominal.
      Abdominal aortic aneurysms (AAAs) and hypertension were more often associated
      with descending than with ascending TAAs (p < 0.001). Aortic growth rate was
      highest for the familial group (0.21 cm/y), intermediate for the sporadic group
      (0.16 cm/y), and lowest for the Marfan group (0.1 cm/y; p < 0.01). CONCLUSIONS:
      TAAs are frequently familial diseases. The predominant mode of inheritance is
      autosomal dominant. Familial TAAs have a relatively early age of onset. Aneurysms
      in relatives may be seen in the thoracic aorta, the abdominal aorta, or the
      cerebral circulation. Screening of first-order relatives of probands with TAA is
      essential. Familial TAAs tend to grow at a higher rate, exemplifying a more
      aggressive clinical entity.

PMID- 16996942
TI  - Invited commentary.

PMID- 16996943
TI  - Reoperations on the ascending aorta and aortic root in patients with previous
      cardiac surgery.
AB  - BACKGROUND: First time operations on the ascending aorta are performed with low
      mortality, few complications, and excellent long-term results. Reoperations for
      aortic pathology in patients with previous cardiac surgery carry significantly
      more risk. Technical issues during the procedure, as well as age, preoperative
      New York Heart Association class, and perioperative renal dysfunction, have been
      shown to contribute heavily to worse outcomes. We analyzed our results with
      aortic reoperations with the intent of further reducing surgical risk through
      alterations in surgical technique or patient selection. METHODS: From July 1997
      until October 2005, 147 patients having previous cardiac surgery presented with
      aneurysm or dissection of the ascending aorta or root. Perioperative data were
      retrospectively analyzed. Morbidity, mortality, and risk factors for these events
      were calculated. RESULTS: Eight patients expired (5.4%) after their reoperation.
      Significant (p < 0.05) univariate risk factors for mortality included age greater
      than 75 years (< 0.001), previous coronary artery bypass grafting (CABG) (<
      0.008), cardiopulmonary bypass greater than 240 minutes (< 0.01), need for
      intraaortic balloon pump support (< 0.001), need for new CABG (< 0.007),
      postoperative cerebrovascular accident (< 0.032), and tracheostomy (< 0.003). Age
      75 years or older (p < 0.025) was the only significant variable for death by
      multivariate analysis. A majority of patients (n = 87, 60%) required circulatory
      arrest to complete their procedure. However, neither arch involvement nor type of
      aortic root procedure was predictive of perioperative mortality. CONCLUSIONS:
      Surgery on the ascending aorta and root in patients who have had previous cardiac
      surgery can be performed with low mortality. Advanced age and significant
      coronary disease may negatively influence surgical results.

PMID- 16996944
TI  - Improved mechanical reliability of the HeartMate XVE left ventricular assist
      system.
AB  - BACKGROUND: The HeartMate XVE left ventricular assist device is a valuable
      treatment option for patients with end-stage heart failure. During the past
      several years, the XVE has undergone a series of design enhancements to improve
      reliability. We compared the reliability of the two most recent design iterations
      of the XVE pump (stitch modification to the inflow valve assembly and new inflow
      valve housing redesign) to the earlier VE version. METHODS: A retrospective
      evaluation of device reliability was performed for 268 devices implanted in 245
      patients (VE: n = 167 devices, 147 patients, implant dates October 16, 1998, to
      December 19, 2003; XVE: n = 101 devices, 98 patients, implant dates August 1,
      2002, to April 14, 2004). RESULTS: Median duration of device support for the VE
      and XVE was 159 days (range, 0 to 1,206 days) and 229 days (range, 0 to 693
      days), respectively (p = 0.495). Significantly fewer major device malfunctions
      occurred within the XVE group as compared with the VE group (6 versus 36,
      respectively; p = 0.0003). The number of major device malfunctions per patient
      year of support for inflow valve dysfunction, bearing wear, and other failures
      for the VE and XVE were 0.2 versus 0.04 (p = 0.006), 0.16 versus 0.01 (p =
      0.005), and 0.06 versus 0.04 (p = 1.000), respectively. The freedom from major
      device malfunction at 1 year was 76% +/- 6% for the VE and 97% +/- 2% for the XVE
      device (p < 0.001). The freedom from death as a result of major device
      malfunction at 1 year was 97% +/- 2% for the VE and 98% +/- 2% for the XVE (p =
      0.698). CONCLUSIONS: Design enhancements to the HeartMate XVE have significantly
      reduced the incidence of major device malfunctions compared with the earlier VE
      model because of a reduction in failure modes from bearing wear and inlet valve
      dysfunction. Further follow-up is necessary to establish the long-term durability
      of the most recent XVE pump version.

PMID- 16996945
TI  - Invited commentary.

PMID- 16996946
TI  - Selection of surgical or percutaneous coronary intervention provides differential
      longevity benefit.
AB  - BACKGROUND: Treatment of coronary artery disease (CAD) is evolving with better
      medications, improvements in percutaneous coronary intervention (PCI), and
      enhanced techniques for coronary artery bypass grafting (CABG). METHODS: In this
      study, 18,481 patients with significant (>75% stenosis) CAD treated at a single
      center between 1986 and 2000 were assigned to one of three groups based on
      initial treatment strategy: medical therapy (MED) (n = 6862), PCI (n = 6292), or
      CABG (n = 5327). Each group was categorized into 3 groups according to baseline
      severity of CAD: low-severity (predominantly 1-vessel), intermediate-severity
      (predominantly 2-vessel), and high-severity (all 3-vessel), and prospectively
      evaluated in Cox models for all-cause mortality adjusted for cardiac risk,
      comorbidity, and propensity for selection of a specific treatment. Treatments
      were compared for the entire period and three eras (1: 1986 to 1990; 2: 1991 to
      1995; 3: 1996 to 2000), the last encompassing widespread availability of PCI with
      stenting. RESULTS: Survival significantly improved in all groups for all degrees
      of CAD, despite increasing severity of illness. Revascularization strategies
      provided significant survival over MED with 8.1, 10.6, and 23.6 additional months
      per 15 years of follow-up for low-severity, intermediate-severity, and high
      severity CAD, respectively. Therapeutic improvements led to increased survival of
      5.3 additional months per 7 years of follow-up (95% confidence interval, 0.2 to
      10.2; p = 0.039) in era 3 for CABG compared with PCI for high-severity CAD.
      CONCLUSIONS: Initial revascularization strategies result in significant survival
      advantage over MED for all CAD levels. Patients with high-severity CAD have
      reduced survival with PCI compared with those initially treated with CABG.

PMID- 16996947
TI  - Piracetam prevents cognitive decline in coronary artery bypass: a randomized
      trial versus placebo.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) can be associated with
      postoperative cognitive impairment and ischemic stroke. No effective treatment is
      currently available. The aim of this study was to evaluate the effectiveness of
      piracetam to treat the cognitive impairment after CABG in an investigator
      initiated, double-blind, placebo-controlled, randomized clinical trial. METHODS:
      Patients undergoing CABG (n = 98) were randomized to placebo (n = 48) or
      piracetam (n = 50). Study drugs were administered intravenously (150 mg/kg daily;
      300 mg/kg on the day of surgery) from the day before surgery to 6 days after
      surgery, then orally (12 g/day) up to 6 weeks after surgery. Cognitive function
      was assessed before surgery (baseline) and 6 weeks after surgery (outcome) by
      using a battery of 12 neuropsychologic tests. The Spielberger Anxiety Inventory
      and the Beck Depression Inventory were also administered. The combined score
      derived from the standardized neuropsychologic assessments was analyzed by using
      an analysis of covariance with baseline and education as covariates. RESULTS: Six
      weeks after surgery, the combined score indicated a statistically significant
      treatment effect in the per protocol population (1.848, p = 0.041) and a tendency
      towards statistical significance in the intent-to-treat population (1.624, p =
      0.064) in the group treated with piracetam, but no statistically significant
      treatment effect was seen in the placebo. The state of anxiety measured by the
      Spielberger Anxiety Inventory was decreased in both groups (-9.27 and -6.37 in
      the placebo and piracetam groups, respectively). CONCLUSIONS: Six weeks after
      CABG, cognition was significantly improved in patients treated with piracetam.
      Additional trials are required to confirm these effects.

PMID- 16996948
TI  - Patterns of postoperative systemic vascular resistance in a randomized trial of
      conventional on-pump versus off-pump coronary artery bypass graft surgery.
AB  - BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) is associated with a
      less intense systemic inflammatory response according to biochemical markers. We
      studied systemic vascular resistance (SVR) as a physiologic response to systemic
      inflammatory response to determine any differences between OPCAB and on-pump
      coronary artery bypass grafting (ONCAB) in a prospective randomized trial.
      METHODS: One hundred consecutive patients were randomized to OPCAB or ONCAB, 50
      in each group. Antifibrinolytics and steroids were not used. All protocols were
      identical except for cardiopulmonary bypass. Temperature, SVR index, cardiac
      index, and blood pressure were measured continuously for the first 24 hours
      postoperatively. All patients were reviewed at 30 days. RESULTS: There was no 30
      day mortality, no stroke, and no acute renal failure. Mean temperature peaked at
      37.5 degrees C at 12 hours (p = 0.700 between groups). Mean SVR index fell to
      1,900 dyne x cm(-5) x m(-2) at 12 to 18 hours; 42% of OPCAB and 32% of ONCAB
      patients developed very low SVR index (<1,500 dyne x cm(-5) x m(-2)). The
      incidence of high SVR (>2,500 dyne x cm(-5) x m(-2)) fell from 20% to 2% by 12 to
      18 hours. The extent and pattern of SVR index responses were similar in both
      groups (p = 0.840). Mean cardiac index peaked at 3.0 L x min(-1) x m(-2), 12 to
      18 hours postoperatively (p = 0.815 between groups); 84% of OPCAB and 90% of
      ONCAB had cardiac index greater than 2.2 L x min(-1) x m(-2) at all times. Only
      10% of patients required vasopressors. Blood pressure responses were also similar
      (p = 0.314). CONCLUSIONS: The incidence of low SVR, and patterns of SVR changes
      were similar in ONCAB and OPCAB, and were clinically unimportant as few patients
      required vasopressor support. Cardiac outputs and clinical outcomes were
      excellent in both groups.

PMID- 16996949
TI  - Invited commentary.

PMID- 16996950
TI  - Off-pump revascularization of chronically occluded left anterior descending
      artery through left anterior small thoracotomy: early and late angiographic and
      clinical follow-up.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate the safety and
      efficacy of left anterior small thoracotomy for treatment of isolated chronic
      total occlusion of the left anterior descending artery. METHODS: From November
      21, 1994, to December 31, 2002, 143 patients with isolated left anterior
      descending artery chronic occlusion underwent off-pump surgery through left
      anterior small thoracotomy. Safety was evaluated analyzing 30-day mortality,
      major adverse cardiac events, and major complications; efficacy was evaluated
      analyzing 6-month angiographic results and 12-month survival, freedom from
      cardiac death, freedom from acute myocardial infarction, either in all areas or
      in the grafted one, freedom from redo or percutaneous coronary intervention,
      freedom from target vessel revascularization, and freedom from major adverse
      cardiac events and from any event. Eight-year outcome was reported as well.
      RESULTS: Thirty-day mortality was 0.7% (1 patient). No patient experienced acute
      myocardial infarction, cerebrovascular accident, or urgent repeat
      revascularization. One-year survival was 98.6% +/- 0.7%; freedom from cardiac
      death was 99.3% +/- 0.7%; freedom from acute myocardial infarction in either all
      areas or in the grafted one was 100%; freedom from redo or percutaneous coronary
      intervention or from target vessel revascularization was 99.3% +/- 0.7%, and
      freedom from major adverse cardiac events or any event was 97.9% +/- 1.2%. Eight
      year survival was 94.9% +/- 1.9%; freedom from cardiac death was 96.3% +/- 1.6%,
      from acute myocardial infarction in all or in the grafted area 99.2% +/- 0.8%,
      from redo or percutaneous coronary intervention 94.4% +/- 2.1, from target vessel
      revascularization 97.8% +/- 1.3%, from major adverse cardiac events 92.8% +/-
      2.2%, and from any event 89.5% +/- 2.7%. Six months after surgery, 56% of
      survivors underwent angiographic control, showing a patency rate of 98.2%.
      CONCLUSIONS: In our experience, left anterior small thoracotomy operation can be
      considered a suitable choice for treatment of left anterior descending artery
      chronic occlusion.

PMID- 16996951
TI  - Invited commentary.

PMID- 16996953
TI  - Invited commentary.

PMID- 16996952
TI  - Mid-term patency after magnetic coupling for distal bypass anastomosis in
      coronary surgery.
AB  - BACKGROUND: The magnetic vascular positioner (MVP), a device for distal bypass
      anastomosis in coronary surgery, was developed to allow a simple and rapid
      procedure and to improve graft patency. We analyze our mid-term results with this
      device. METHODS: Eighteen distal anastomoses were performed by using the MVP, and
      18 with a hand-sewn technique were completed in 11 patients. The target arteries
      for the MVP anastomosis were the left anterior descending in 9 patients, a
      marginal branch in 4, a diagonal branch in 3, and right coronary artery in 2. The
      left internal thoracic artery was used as graft in 9 patients, saphenous vein in
      6, right internal thoracic artery in 2, and radial artery in 1. RESULTS: Coronary
      angiography was performed at discharge and after a complete follow-up of 19 +/-
      3.5 months. Patency at follow-up was 83.3% (15/18) for MVP anastomoses and 100%
      (18/18) for hand-sewn anastomoses. All occluded MVP anastomoses were performed
      with small-size devices. In one patient, a high-grade left main stenosis was
      overestimated. Competitive flow may be suspected in this case as a cause of graft
      occlusion. No deaths occurred during hospital stay or during follow-up. Freedom
      from reintervention was 100%. CONCLUSIONS: The MVP is the only mechanical
      connector for distal anastomoses applicable for all kind of grafts, for all
      coronary artery locations, and with both end-to-side and side-to-side technique.
      Mid-term patency of MVP anastomoses is acceptable but inferior to the patency of
      hand-sewn anastomoses. Occlusion of MVP supplied grafts may be produced by small
      device size.

PMID- 16996954
TI  - Vein graft harvesting induces inflammation and impairs vessel reactivity.
AB  - BACKGROUND: Saphenous veins are often used for coronary artery bypass grafting
      (CABG), but loss of patency is a problem. The surgical procedure may contribute
      to graft injury. Our aim was to study the impact of surgical handling of
      saphenous veins on graft inflammation and vascular function. METHODS: Biopsy
      samples of saphenous veins were taken from 9 patients undergoing elective CABG at
      the start of vein harvesting (open technique) and after the last proximal
      anastomosis was sutured. Messenger RNA was extracted and amplified with
      semiquantitative reverse transcription polymerase chain reaction. Gene expression
      of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta),
      leukocyte adhesion molecules (E-selectin, intercellular adhesion molecule-1), and
      vasoactive substances (endothelin-1, inducible and endothelial nitric oxide
      synthase) was investigated. Translocation of nuclear factor-kappaB (NFkappaB) was
      evaluated with electrophoretic mobility shift assay. Immunostaining for von
      Willebrand factor was performed to evaluate loss of endothelium, and in vitro
      vein reactivity to phenylephrine and endothelin-1 was studied. RESULTS: Gene
      expression of cytokines and leukocyte adhesion molecules increased after graft
      harvesting and storage, whereas vasoactive substances did not change. Nuclear
      translocation of NFkappaB occurred after surgical handling, concurrent with
      partial loss of endothelium and impaired contractile function. CONCLUSIONS:
      Standard surgical handling of vein grafts induces NFkappaB-driven inflammation in
      the vessel wall and impairs vascular function. This may potentially contribute to
      both early and late graft occlusion.

PMID- 16996955
TI  - Engineered living blood vessels: functional endothelia generated from human
      umbilical cord-derived progenitors.
AB  - BACKGROUND: Tissue-engineered living blood vessels (TEBV) with growth capacity
      represent a promising new option for the repair of congenital malformations. We
      investigate the functionality of TEBV with endothelia generated from human
      umbilical cord blood-derived endothelial progenitor cells. METHODS: Tissue
      engineered living blood vessels were generated from human umbilical cord-derived
      myofibroblasts seeded on biodegradable vascular scaffolds, followed by
      endothelialization with differentiated cord blood-derived endothelial progenitor
      cells. During in vitro maturation the TEBV were exposed to physiologic
      conditioning in a flow bioreactor. For functional assessment, a subgroup of TEBV
      was stimulated with tumor necrosis factor-alpha. Control vessels endothelialized
      with standard vascular endothelial cells were treated in parallel. Analysis of
      the TEBV included histology, immunohistochemistry, biochemistry (extracellular
      matrix analysis, DNA), and biomechanical testing. Endothelia were analyzed by
      flow cytometry and immunohistochemistry (CD31, von Willebrand factor,
      thrombomodulin, tissue factor, endothelial nitric oxide synthase). RESULTS:
      Histologically, a three-layered tissue organization of the TEBV analogous to
      native vessels was observed, and biochemistry revealed the major matrix
      constituents (collagen, proteoglycans) of blood vessels. Biomechanical properties
      (Young's modulus, 2.03 +/- 0.65 MPa) showed profiles resembling those of native
      tissue. Endothelial progenitor cells expressed typical endothelial cell markers
      CD31, von Willebrand factor, and endothelial nitric oxide synthase comparable to
      standard vascular endothelial cells. Stimulation with tumor necrosis factor-alpha
      resulted in physiologic upregulation of tissue factor and downregulation of
      thrombomodulin expression. CONCLUSIONS: These results indicate that TEBV with
      tissue architecture and functional endothelia similar to native blood vessels can
      be successfully generated from human umbilical cord progenitor cells. Thus, blood
      derived progenitor cells obtained before or at birth may enable the clinical
      realization of tissue engineering constructs for pediatric applications.

PMID- 16996956
TI  - Reduction and redistribution of gap and adherens junction proteins after ischemia
      and reperfusion.
AB  - BACKGROUND: Previous studies have demonstrated that alterations in myocardial
      structure, consistent with tissue and sarcomere disruption as well as myofibril
      dissociation, occur after myocardial ischemia and reperfusion. In this study we
      determine the onset of these structural changes and their contribution to
      electrical conduction. METHODS: Langendorff perfused rabbit hearts (n = 47) were
      subjected to 0, 5, 10, 15, 20, 25, and 30 minutes global ischemia, followed by
      120 minutes reperfusion. Hemodynamics were recorded and tissue samples were
      collected for histochemical and immunohistochemical studies. Orthogonal
      epicardial conduction velocities were measured, with temperature controlled, in a
      separate group of 10 hearts subjected to 0 or 30 minutes of global ischemia,
      followed by 120 minutes of reperfusion. RESULTS: Histochemical and quantitative
      light microscopy spatial analysis showed significantly increased longitudinal and
      transverse interfibrillar separation after 15 minutes or more of ischemia (p <
      0.05 versus control). Confocal immunohistochemistry and Western blot analysis
      demonstrated significant reductions (p < .05 versus control) of the intercellular
      adherens junction protein, N-cadherin, and the active phosphorylated isoform of
      the principal gap junction protein, connexin 43 at more than 15 minutes of
      ischemia. Cellular redistribution of connexin 43 was also evidenced on
      immunohistochemistry. No change in integrin-beta1, an extracellular matrix
      attachment protein, or in epicardial conduction velocity anisotropy was observed.
      CONCLUSIONS: These data indicate that there are significant alterations in the
      structural integrity of the myocardium as well as gap and adherens junction
      protein expression with increasing global ischemia time. The changes occur
      coincident with previously observed significant decreases in postischemic
      functional recovery, but are not associated with altered expression of matrix
      binding proteins or electrical anisotropic conduction.

PMID- 16996957
TI  - Biologically variable bypass reduces enzymuria after deep hypothermic circulatory
      arrest.
AB  - BACKGROUND: Renal injury is common after open-heart surgery. Cardiopulmonary
      bypass contributes to the problem. We compared conventional nonpulsatile
      perfusion (NP) to biologically variable perfusion (BVP), which uses a computer
      controller to restore physiological beat-to-beat variability to roller pump flow.
      We hypothesized BVP would decrease renal injury after deep hypothermic
      circulatory arrest. METHODS: Pigs were randomly assigned to either BVP (n = 9) or
      NP (n = 9), cooled, arrested at 18 degrees C (1 hour), reperfused, and rewarmed
      and maintained normothermic (3 hours). Additional pigs had NP for a similar time
      as above, but without circulatory arrest (n = 3), or were sham-treated without
      bypass (n = 3). Hemodynamics, acid-base status, temperature, and urine volumes
      were measured. Urinary enzyme markers of tubular injury were compared post-hoc
      for gamma glutamyl transpeptidase, alkaline phosphatase, and glutathione S
      transferase and by urine proteomics using mass spectrometry. RESULTS: Urine
      output at 1 hour after arrest was 250 +/- 129 mL with BVP versus 114 +/- 66 mL
      with NP (p < 0.02). All three renal enzyme markers were higher with NP after
      arrest compared with BVP. In animals on bypass without arrest or those sham
      treated, no elevations were seen in renal enzymes. Urine proteomics revealed
      abnormal proteins, persisting longer with NP. Biologically variable perfusion
      decreased cooling to 21.0 +/- 9.0 minutes versus 31.7 +/- 7.5 minutes (p <
      0.002), and decreased rewarming to 22.1 +/- 3.9 minutes versus 31.2 +/- 5.1
      minutes (p < 0.002). CONCLUSIONS: Biologically variable perfusion improved urine
      output, decreased enzymuria, and attenuated mass spectrometry urine protein
      signal with more rapid temperature changes. This strategy could potentially
      shorten bypass duration and may decrease renal tubular injury with deep
      hypothermic circulatory arrest.

PMID- 16996958
TI  - Invited commentary.

PMID- 16996959
TI  - Development of a novel temporary epicardial pacing wire with biodegradable film.
AB  - PURPOSE: A temporary epicardial pacing wire (TEPW) has been routinely placed in
      patients undergoing cardiac surgery. However, its fixation or removal
      occasionally causes troublesome complications. The aim of this study is to
      develop a novel TEPW using biodegradable film to fix the electrode to the
      epicardium without needle stabbing. DESCRIPTION: A biodegradable film was
      prepared with poly(L-lactide-co-epsilon-caprolactone). The film has a honeycomb
      patterned structure that serves as a temporary adhesive for the myocardial
      surface, and the electrode was incorporated within the film. The novel TEPW was
      placed on the ventricular epicardium of dogs (group A, n = 5). As a control,
      conventional TEPW was inserted (group B, n = 6). The pacing threshold, R wave
      amplitude, impedance, and slew rate were measured at postoperative days 0, 1, 3,
      5, 7, and 14, and complications after removal were checked. EVALUATION: All
      measurements in both groups were identified and differences were not observed. In
      addition, the novel TEPWs could be easily removed without related complications.
      CONCLUSIONS: This novel TEPW is safe and feasible for postoperative management of
      cardiac surgeries.

PMID- 16996960
TI  - Invited commentary.

PMID- 16996961
TI  - A wire-cutting clamp designed to reduce complications during sternotomy closure.
AB  - PURPOSE: Sternal wire placement frequently results in glove disruption, wound
      contamination and personnel skin puncture. The described cutting clamp was
      developed to simplify sternotomy closure and reduce complications. DESCRIPTION:
      Informed consent was obtained from 103 patients who underwent a variety of common
      cardiac surgical procedures. In each instance, once the cardiac portion of the
      procedure was completed, the median sternotomy was closed using standard sternal
      wires and the described cutting clamps. A single set of clamps was repeatedly re
      sterilized and used for all cases. EVALUATION: There were no incidents of
      unintentional clamp release, glove disruption or personnel skin punctures from
      the wire. None of the patients had clinically evident sternal wound infections or
      nonunion. There were no deaths. The functional attributes of the clamps remained
      constant throughout the study, and no significant wear was detected on the
      carbide inserts or other components of the clamps. CONCLUSIONS: The sternal wire
      cutting clamp simplifies sternal closure and should reduce complications.

PMID- 16996962
TI  - Congenital bronchial atresia associated with spontaneous pneumothorax.
AB  - A 36-year-old woman presented with left chest pain and frequent symptoms of upper
      respiratory infection. Chest roentgenograms revealed a left pneumothorax and
      apical bulla, and hyperlucency in the left pulmonary field. She was diagnosed
      with congenital bronchial atresia associated with a left spontaneous
      pneumothorax. A thoracoscopy-assisted left superior segmentectomy was performed.
      There was no recurrence of the pneumothorax or symptoms of recurrent upper
      respiratory infection at the 1-year follow-up examination. Bulla formation was
      believed to have resulted from emphysematous changes in the peripheral lung due
      to congenital bronchial atresia. The pneumothorax may have occurred due to
      rupture of the bulla.

PMID- 16996963
TI  - Massive spontaneous hemothorax associated with Von Recklinghausen's disease.
AB  - A 30-year-old woman with Von Recklinghausen's disease was admitted to our
      hospital because of sudden onset of dyspnea and syncope. A chest roentgenogram
      showed a massive right pleural effusion and insertion of an intercostal tube
      drained 1,600 cc of blood. A computed tomographic chest scan with contrast
      revealed a hyperdense mass in the right paravertebral area. At thoracotomy,
      retained clotted hemothorax and continued bleeding from tumor vessels was noted.
      The apex of the right hemithorax and the tumor location was packed. The
      pathologic diagnosis was ganglioneuroma and follow-up of the patient for 2 years
      after re-thoracotomy and removal of the packs revealed no complication and
      morbidity. We report this case to emphasize the importance of early recognition
      and prompt surgical intervention in spontaneous hemothorax associated with Von
      Recklinghausen's disease.

PMID- 16996964
TI  - Elastofibroma dorsi as differential diagnosis in tumors of the thoracic wall.
AB  - We report the case of a 73-year-old woman who presented with a soft tissue tumor
      located between the scapula and the rib cage. Magnetic resonance imaging showed
      an inhomogeneous tumor on the right dorsolateral thoracic wall that measured 7 x
      4 x 7 cm with contrast enhancement. The findings were suggestive of partial
      infiltration of intercostal muscles and were suspicious of a malignant tumor.
      After local excision at a district hospital had failed to render definitive
      diagnosis, the patient underwent complete resection of the tumor at our
      institution. Histology from the specimen was consistent with elastofibroma dorsi
      with free resection margins.

PMID- 16996966
TI  - Limited surgery and radiofrequency ablation for recurrent lung cancer.
AB  - A 72-year-old man who had been diagnosed with second recurrent lung cancer was
      referred for consideration of a surgical resection. He had undergone a right
      upper lobectomy with bronchoplasty for the primary lung cancer and stereotactic
      radiation therapy for the first recurrent tumor. Owing to the comorbid diseases,
      video-assisted wedge resection and radiofrequency ablation were performed for the
      second recurrent tumor. The postoperative course was uneventful and the patient
      was discharged home without complaints. Eighteen months after surgery, he is
      alive without recurrence. These procedures are minimally invasive and may
      decrease the local recurrence of lung cancer in properly selected patients.

PMID- 16996965
TI  - Pulmonary angiomyolipoma.
AB  - Extrarenal angiomyolipoma are benign lesions that have rarely been described in
      the thorax. We present the clinical, radiographic, and pathologic findings of a
      pulmonary angiomyolipoma in a 63-year-old woman who had no diagnosis of tuberous
      sclerosis or lymphangioleiomyomatosis. We believe that this report is one of the
      first descriptions of angiomyolipoma of the lung.

PMID- 16996967
TI  - Multiple lung adenocarcinomas showing ground-glass opacities on thoracic computed
      tomography.
AB  - It is difficult to distinguish multiple primary lung cancers from pulmonary
      metastasis. We experienced a case of surgically resected lung tumors that showed
      multiple ground-glass opacities on thoracic computed tomographic scan. There were
      eight nonsolid and two part-solid ground-glass opacities in the bilateral lungs.
      Surgical resection was performed because all tumors had a ground-glass opacity
      appearance on computed tomographic scan, which is compatible with a finding of
      primary lung adenocarcinoma. The postoperative pathologic diagnoses were two
      cases of invasive adenocarcinoma, six cases of bronchioloalveolar carcinoma, and
      eight cases of atypical adenomatous hyperplasia. The patient remains alive
      without any evidence of recurrence 40 months after surgery. A ground-glass
      opacity appearance on computed tomographic scan could be interpreted as
      supportive evidence for multiple primary lung adenocarcinoma rather than
      pulmonary metastases.

PMID- 16996968
TI  - How fast does an atrial myxoma grow?
AB  - We describe the case of a 58-year-old man who underwent coronary artery bypass
      grafting with an unremarkable transesophageal echocardiogram. Three years later
      he underwent a routine transthoracic echocardiogram that was normal. Eleven
      months later he presented with dyspnea and right-sided heart failure.
      Transthoracic echocardiogram showed a large mass located in the right atrium in
      which the base was inserted by the junction of the inferior vena cava and
      coronary sinus. Pathology showed a myxoma that measured 15 x 3 cm implying a
      growth rate of 1.36 x 0.3 cm/month.

PMID- 16996969
TI  - Giant cardiac fibroma.
AB  - A 29-year-old woman who presented with persistent ventricular premature beat
      during her delivery was referred to us. Her cardiac echocardiography showed a
      giant tumor located in the posterior wall of the left ventricle. She had no
      symptoms of heart failure. Partial resection of the mass was safely conducted
      using cardiopulmonary bypass. The histopathologic finding was fibroma. She has
      been doing well 6 years after operation. Periodic echocardiography has showed no
      growth in this tumor.

PMID- 16996970
TI  - Left atrial sarcoma: resection and repair by cardiac autotransplant and in situ
      pericardial patch.
AB  - This report demonstrates the method of resection of a left atrial tumor involving
      the right superior pulmonary vein. The unique features are use of adjacent
      pericardium as an in situ patch to reconstruct the left atrium when there is no
      margin of left atrium remaining on the pulmonary veins and cardiac
      autotransplantation.

PMID- 16996971
TI  - Single-stage resection of a mixed endometrial stromal sarcoma and smooth muscle
      tumor with intracardiac and pulmonary extension.
AB  - A case of mixed endometrial stromal sarcoma and smooth muscle cell tumor of the
      uterus with intravenous extension into the right heart and pulmonary artery is
      presented. The current literature and diagnostic and therapeutic strategies of
      pelvic tumors with intravenous extension are reviewed.

PMID- 16996972
TI  - Tuberculous pericardial effusion after coronary artery bypass graft.
AB  - We describe a case of a recurrent pericardial effusion after coronary artery
      bypass grafting. This was initially considered to be due to post-pericardiotomy
      syndrome, but was later treated empirically as tuberculosis. After definitive
      surgery for this condition, pericardial histology and immunohistochemistry
      confirmed the diagnosis of tubercular pericarditis. At 4-months follow-up, while
      continuing anti-tuberculous therapy and corticosteroids, the patient showed
      consistent improvement without further recurrence of his pericardial effusion.
      Local reactivation of tuberculosis after pericardiotomy has not been previously
      reported and merits careful consideration in population groups in which
      tuberculosis is highly endemic.

PMID- 16996973
TI  - Aortocoronary shunting during off-pump coronary artery bypass surgery as acute
      reperfusion strategy in ST-elevation myocardial infarction.
AB  - We report the case of a 43-year-old patient with acute ST-segment elevation
      anterior myocardial infarction who underwent off-pump coronary artery bypass
      grafting. To reduce the duration of ongoing myocardial ischemia, acute
      reperfusion of the infarcted coronary artery was achieved using an aortocoronary
      shunt, thereby perfusing the occluded left anterior descending artery. Under the
      protection of the aortocoronary shunt, the left internal thoracic artery was
      harvested and was thereafter anastomosed to the left anterior descending artery.
      The patient had an uneventful postoperative recovery.

PMID- 16996974
TI  - Iatrogenic type A dissection after attempted stenting of a descending aortic
      aneurysm.
AB  - This case demonstrates an iatrogenic acute retrograde type A dissection of the
      aortic arch and ascending aorta during elective endovascular stenting of a
      proximal descending aortic aneurysm. This devastating complication necessitated
      emergent surgery with unfavorable postoperative outcome. Other than the known
      causes, the described retrograde type A dissection resulted from guidewire
      manipulation and iatrogenic creation of a false lumen, which was erroneously
      dilated and stented.

PMID- 16996975
TI  - Austrian triad with sinus of Valsalva aneurysm and rupture.
AB  - An interesting case of a young patient presenting with Austrian's Triad:
      pneumococcal pneumonia, pneumococcal meningitis, and pneumococcal endocarditis.
      On echocardiogram the patient was noted to have a noncoronary sinus of Valsalva
      aneurysm and vegetations on the aortic cusps resulting in disruption of valvular
      integrity and severe aortic insufficiency. Color Doppler also revealed rupture of
      the aneurysm into the right atrium. The patient was taken to surgery where the
      noncoronary cusp was noted to be completely replaced with vegetative lesions. The
      aortic valve was replaced with a No. 21 Carpentier-Edwards bioprosthetic valve
      (Edwards Lifesciences, Irvine, CA), and the noncoronary sinus of Valsalva was
      repaired with concomitant closure of the fistula using glutaraldehyde autologous
      pericardium.

PMID- 16996976
TI  - Leakage of the arterial prosthesis of an Impella RVAD.
AB  - Seromas occurring around a vascular graft are a rare complication. We report a
      life-threatening plasma leakage that occurred through the polytetrafluoroethylene
      vascular prosthesis of an Impella right ventricular assist device (Impella RD
      [Impella Cardiosystems GmbH, Aachen, Germany]) implanted in a 62-year-old patient
      with acute right ventricular failure after cardiac transplantation. The leakage
      became progressively massive. Weaning the patient from the right ventricular
      assist device was not possible. The prosthesis was thus wrapped within a
      pericardial patch to contain the leakage. Three days later the patient could be
      successfully weaned and the pump was removed. The clinical evolution was
      favorable.

PMID- 16996977
TI  - Levosimendan reversing low output syndrome after heart transplantation.
AB  - After heart transplantation primary graft failure is a major cause of early
      mortality. Treatment options include inotropes and mechanical assist devices.
      Developing better methods would impact on patients' short- and long-term
      survival. We present a case of primary graft failure manifested as cardiogenic
      shock unresponsive to catecholamines and a phosphodiesterase inhibitor. Reversal
      of low output syndrome was achieved with a new type of inotropic agent,
      levosimendan, leading to the later complete recovery.

PMID- 16996978
TI  - Multiple cardiac inflammatory myofibroblastic tumors in the right ventricle in an
      infant.
AB  - Reported is the successful treatment of a 2-month-old boy with multiple
      inflammatory myofibroblastic tumors in the right ventricle protruding into the
      right atrium through the tricuspid annulus. The patient underwent subtotal
      excision on cardiopulmonary bypass with no intraoperative or postoperative
      complications. Cardiac inflammatory myofibroblastic tumors are rare lesions, and
      surgical resections in patients as young as 2 months have not been previously
      described. In this report we review the relevant literature and discuss the
      prevalence, histology, pathogenesis, clinical manifestations, diagnosis,
      differential diagnosis, and treatment of cardiac inflammatory myofibroblastic
      tumor.

PMID- 16996979
TI  - Transplantation in truncus arteriosus combined with interrupted aortic arch.
AB  - We present the case of an infant with truncus arteriosus combined with a
      dysplastic truncal valve not amenable to repair and interrupted aortic arch. Due
      to the disappointing results of truncal valve replacement we decided to perform
      cardiac transplantation. The infant survived transplantation and was discharged 4
      weeks after surgery.

PMID- 16996980
TI  - Large tricuspid mass in primary antiphospholipid syndrome.

PMID- 16996981
TI  - A lifelong systolo-diastolic murmur.

PMID- 16996982
TI  - Variations in the technique of slide tracheoplasty to repair complex forms of
      long-segment congenital tracheal stenoses.
AB  - Slide tracheoplasty has become the preferred technique for repair of long-segment
      congenital tracheal stenosis with complete tracheal rings. Complex morphological
      subtypes require technical modifications, which we present as follows.

PMID- 16996983
TI  - Modified central line for pneumothorax.
AB  - Pneumothoraxes, whether spontaneous or iatrogenic, frequently require drainage.
      Although the recent trend has been toward a catheter-based approach, many
      thoracic surgeons continue to use chest tubes. Tube thoracostomy is associated
      with significant pain at the time of insertion and during continued drainage.
      Pneumothorax catheters are less painful but more expensive, and some have been
      associated with significant failure. After disappointing experience with
      pneumothorax catheters, we have modified a central line to use in lieu of a
      pneumothorax kit. We have found this technique to be effective, safe, reliable,
      and inexpensive.

PMID- 16996984
TI  - Self-made tracheal stomal stent using a tracheal T-tube.
AB  - Adapting a silicone tracheal safe T-tube is a simple method to guarantee upper
      airway permeability. Its making and availability ease offers a cheap and valid
      option to avoid the complications of the tracheostomy tube.

PMID- 16996985
TI  - Minimally invasive technique for explantation of right ventricular assist
      devices.
AB  - In an attempt to reduce some or all of the complications resulting from the use
      of biventricular assist devices after mechanical circulatory support, we have
      developed and applied a minimally invasive technique for explantation of right
      ventricular assist devices.

PMID- 16996986
TI  - Repair of the damaged heart by bone marrow cells: from experimental evidence to
      clinical hope.
AB  - Heart failure remains the leading cause of death in developed countries in spite
      of improvements in medical and surgical treatments. However, recent observations
      in experimental studies that bone marrow cells may repair cardiac tissue have
      offered renewed hopes for the treatment of heart failure. This optimism is
      further supported by encouraging results from some clinical trials, although the
      degree of benefits, the underlying mechanisms, and the cell types involved remain
      to be elucidated. This review summarizes the relevant experimental and clinical
      studies supporting the use of bone marrow cells in myocardial repair, as well as
      the controversies and challenges encountered.

PMID- 16996987
TI  - Controversies in the use of intraluminal shunts during off-pump coronary artery
      bypass grafting surgery.
AB  - Technical advances have made the performance of multivessel off-pump coronary
      artery bypass feasible. Snaring and intraluminal shunts are the techniques used
      for vascular control. Snaring provides a bloodless surgical field, is usually
      well tolerated by the patient, and is supported by years of clinical experience.
      Intraluminal shunts aim to achieve hemostasis at the arteriotomy site and to
      allow antegrade flow to provide myocardial protection. There are unresolved
      issues regarding whether shunts have a clinical benefit, do provide adequate flow
      to provide myocardial protection, and whether they cause significant endothelial
      damage. In this article, we have reviewed the literature to lend perspective to
      these issues.

PMID- 16996988
TI  - Dr Andrew Logan: the passing of a pioneer.

PMID- 16996990
TI  - Prevalence of delayed gastric emptying and gastroesophageal reflux in patients
      with end-stage lung disease.

PMID- 16996991
TI  - Combined carotid and coronary surgery: early and late results.

PMID- 16996993
TI  - Resveratrol or higher arterial blood pressure protects the spinal cord from
      ischemia-reperfusion injury?

PMID- 16996994
TI  - Early postoperative anticoagulation: more questions than answers?

PMID- 16996997
TI  - Does the combination of aprotinin and angiotensin-converting enzyme inhibitor
      cause renal failure after cardiac surgery?

PMID- 16996998
TI  - Familial cardiac angiosarcoma.

PMID- 16996999
TI  - Special issue: Molecular mechanisms of schizophrenia.

PMID- 16997000
TI  - A single nucleotide polymorphism fine mapping study of chromosome 1q42.1 reveals
      the vulnerability genes for schizophrenia, GNPAT and DISC1: Association with
      impairment of sustained attention.
AB  - BACKGROUND: The marker D1S251 of chromosome 1q42.1 showed significant association
      with schizophrenia in a Taiwanese sample. We used single nucleotide polymorphism
      (SNP) fine mapping to search for the vulnerability genes of schizophrenia.
      METHODS: We selected 120 SNPs covering 1 Mb around D1S251 from the public
      database. These selected SNPs were initially validated if allele frequency was
      >10%. Forty-seven validated SNPs were genotyped in 102 families with at least 2
      siblings affected with schizophrenia. RESULTS: Two SNP blocks showed significant
      association with schizophrenia. Block 1 (five-SNP), located between intron 2 and
      intron 13 of the glyceronephosphate O-acyltransferase (GNPAT) gene, showed the
      most significant associations using single-locus TDT (z = -2.07, p = .038, df =
      1) and haplotype association analyses (z = -1.99, p = .046, df = 1). Block 2 (two
      SNP), located between intron 4 and intron 5 of the disrupted-in-schizophrenia 1
      (DISC1) gene, also showed the most significant results in both the single-locus
      (z = -3.22, p = .0013, df = 1) and haplotype association analyses (z = 3.35, p =
      .0008, df = 1). The association of the DISC1 gene with schizophrenia was mainly
      in the patient group with sustained attention deficits as assessed by the
      Continuous Performance Test. CONCLUSIONS: Chromosome 1q42.1 harbors GNPAT and
      DISC1 as candidate genes for schizophrenia, and DISC1 is associated with
      sustained attention deficits.

PMID- 16997001
TI  - Clozapine enhances prepulse inhibition in healthy humans with low but not with
      high prepulse inhibition levels.
AB  - BACKGROUND: Atypical antipsychotics have been assessed for normalization effects
      on deficient sensory gating as indexed by prepulse inhibition (PPI) in
      schizophrenics with generally positive, although somewhat conflicting, results.
      METHODS: We tested the acute effect of clozapine on startle, PPI, and attention,
      working memory, and executive functioning in 28 healthy male volunteers with low
      versus high PPI levels using a placebo-controlled within-subject design. RESULTS:
      Clozapine significantly increased PPI levels obtained at short lead intervals of
      60 and 120 msec in subjects with low PPI performance but showed no effect in
      subjects with high PPI. Clozapine also caused a mild cognitive impairment on
      attention and pattern recognition memory tests. No correlations between cognitive
      measures and PPI performance were found. Moreover, low and high PPI performers
      were shown to exhibit stable levels of PPI across three separate nondrug testing
      days. CONCLUSIONS: Clozapine increases sensorimotor gating in healthy subjects
      with low but not high PPI levels in a manner comparable to that seen in clozapine
      treated schizophrenia patients. Healthy subjects with low PPI level in
      combination with genetic studies may provide a translational model to elucidate
      the neuronal basis of PPI deficits and to test the efficacy of novel
      antipsychotic medication.

PMID- 16997002
TI  - Critical factors in gene expression in postmortem human brain: Focus on studies
      in schizophrenia.
AB  - BACKGROUND: Studies of postmortem human brain are important for investigating
      underlying pathogenic molecular mechanisms of neuropsychiatric disorders. They
      are, however, confounded by pre- and postmortem factors. The purpose of this
      study was to identify sources of variation that will enable a better design of
      gene expression studies and higher reliability of gene expression data. METHODS:
      We assessed the contribution of multiple variables to messenger RNA (mRNA)
      expression of reference (housekeeping) genes measured by reverse transcriptase
      polymerase chain reaction (RT-PCR) by multiple regression analysis in a large
      number (N = 143) of autopsy samples from the hippocampus and white and grey
      matter of the dorsolateral prefrontal cortex (DLPFC) of patients with
      schizophrenia and normal control subjects. RESULTS: The strongest predictor of
      gene expression was total RNA quality. Other significant factors included pH,
      postmortem interval, age and the duration of the agonal state, but the importance
      of these factors depended on transcript measured, brain region analyzed, and
      diagnosis. The quality of RNA obtained from the DLPFC white matter was also
      adversely affected by smoking. CONCLUSIONS: Our results show that normalization
      of expression data of target genes with a geometric mean of multiple housekeeping
      genes should be used to control for differences in RNA quality between samples.
      The results also suggest that accurate assessment of other confounding factors
      and their inclusion as regressors in the analysis is critical for obtaining
      reliable and accurate quantification of mRNA expression.

PMID- 16997003
TI  - Experimental Coxiella burnetii infection in pregnant goats: a histopathological
      and immunohistochemical study.
AB  - Pregnant goats were inoculated subcutaneosly with Coxiella burnetii and the
      course of infection was studied. Abortion in the last third of pregnancy occurred
      in all infected animals. Tissues from the placenta and other organs were studied
      before and after abortion by immunohistochemistry and PCR analysis. After
      infection, mild lesions were observed in several maternal organs, mainly the
      mammary gland but also the lung and the liver. The trophoblast cells of the
      choriallantoic membrane were the first target cells of the placenta; there was,
      however, a substantial delay between initial infection and placental
      colonization. In the last weeks of pregnancy, just before abortion, massive
      bacterial multiplication was detected in the placenta. In this stage of infection
      a necrotic and suppurative placentitis separated the fetal trophoblast cells from
      maternal syncytial epithelium. Vasculitis was observed in the fetal mesenchyme. A
      strong maternal T-cell response was detected in the inter-placentomal areas but
      not in the placentomes, where only neutrophils and smaller numbers of macrophages
      were associated with the lesions. Neither lesions nor C. burnetii DNA were found
      in maternal organs in animals maintained until day 120 post-abortion.

PMID- 16997004
TI  - Histopathological and immunohistochemical features of natural goat scrapie.
AB  - Histopathological and immunohistochemical examinations were performed on the
      brain and spinal cord of 37 goats from two Greek herds in which scrapie had been
      reported. Of the 37 animals, 18 were from a herd consisting only of goats and 19
      were from a herd of goats mixed with sheep. The goats studied were grouped on the
      basis of the presence or absence of clinical signs. Distinctive lesions and
      PrP(sc) (PrP, prion protein) deposition were found in the central nervous system
      (CNS) of eight clinically affected animals and six symptomless animals. The
      lesion profile and PrP(sc) distribution varied both between and within groups,
      variation being particularly pronounced in the symptomless goats. The results
      concerning the latter group suggested a poor correlation between the intensity of
      lesions, the amount of PrP(sc) in the CNS, and the manifestation of clinical
      signs. Immunohistochemical examination revealed 10 different PrP(sc) types, four
      of which are reported for the first time in goats. All scrapie-affected animals
      carried the VV(21)II(142)HH(143)RR(154) genotype, with the exception of two goats
      that carried the HR(143) dimorphism and had detectable PrP(sc) deposits. The
      results suggest that the histopathological and immunohistochemical profile of the
      natural disease in goats is influenced by the PrP genotype and age of the animals
      but may not be directly associated with the presence or otherwise of clinical
      signs.

PMID- 16997005
TI  - Characterization of the immune response in the placenta of cattle experimentally
      infected with Neospora caninum in early gestation.
AB  - A serial examination of three groups of cattle infected intravenously (iv) (Group
      1, n=8) or subcutaneously (sc) (Group 2, n=8) with live Neospora caninum
      tachyzoites or with VERO cells (Group 3, n=8) at 70 days' gestation was carried
      out and the nature of the inflammatory responses in the placenta and the presence
      of parasite antigen were analysed. Immune cells expressing CD3, CD4, CD8, gamma
      delta (gammadelta) T-cell receptors (TCR), CD79alpha cytoplasmic (cy) (B cells)
      and NKp46 [natural killer (NK) cells] antigens were identified
      immunohistochemically and cells expressing mRNA for interferon-gamma (IFN-gamma)
      were labelled by in-situ hybridization. Intravenous inoculation caused mortality
      in all fetuses from 28 days post-inoculation (dpi) onwards. Subcutaneous
      inoculation caused mortality in 50% of the animals by 28dpi. Pathological changes
      in the placenta consisted of necrosis of fetal placental villi, necrosis and
      inflammation in adjacent areas of the maternal septum and inflammation at the
      base of the maternal caruncle. The inflammatory infiltrate consisted mainly of
      CD3(+) lymphocytes, dominated by CD4(+) and gammadelta TCR(+) cells, with CD8(+)
      cells present to a lesser extent. The results from the control group indicated
      fewer NK cells than those occurring in the placenta of human beings or mice.
      Infiltration of CD4(+) cells and NKp46(+) cells was observed in the caruncular
      base and septa 14 days after infection, whereas infiltration of gammadelta TCR(+)
      cells was observed from 28 dpi onwards. To our knowledge this is the first report
      on the presence and distribution of NK cells in the bovine placenta. Maternal
      inflammatory cells expressing mRNA for IFN-gamma were identified in animals
      inoculated with parasites iv or sc at 14 and 28 dpi, respectively. In the sc
      inoculated dams with live fetuses at 28, 42 and 56dpi, there was no evidence of
      parasite antigen, infiltration of immune cells or production of IFN-gamma,
      suggesting that the parasite had not reached the placenta. The exact cause of
      fetal death was not established. Tissue destruction by the parasite may have
      occurred; in addition, there may have been a T helper 1 (Th-1) immune response to
      the neospora infection at the materno-fetal interface, resulting in infiltrations
      of CD4T cells, gammadelta T cells and NK cells and the subsequent production of
      IFN-gamma. It is possible that a pro-inflammatory Th-1 response early in
      gestation protects the dam by eliminating the parasite; however, it may lead to
      destruction of the placental tissues themselves and thus be incompatible with
      fetal survival.

PMID- 16997006
TI  - Endogenous lipid pneumonia in a dog.
AB  - Endogenous lipid pneumonia has previously been diagnosed in dogs only once. This
      report describes a case in a dog with a persistent cough, in which the
      histological diagnosis was based on the presence of numerous foamy macrophages
      that filled the alveoli and contained small sudanophilic vacuoles. The appearance
      of endogenous lipid pneumonia in this animal was accompanied by Dirofilaria
      immitis infection and chronic bronchitis.

PMID- 16997008
TI  - Milestones leading to the genetic engineering of baculoviruses as expression
      vector systems and viral pesticides.
AB  - The baculovirus expression vector system (BEVS) is widely established as a highly
      useful and effective eukaryotic expression system. Thousands of soluble and
      membrane proteins that, in general, are correctly folded, modified, sorted and
      assembled to produce highly authentic recombinant proteins have been cloned and
      expressed. This historical chronology and perspective will focus on the original,
      peer-reviewed discoveries that were pioneering and seminal to the development of
      the BEVS and that provided the basis for subsequent and more recent developments
      and applications.

PMID- 16997009
TI  - Polydnavirus genes that enhance the baculovirus expression vector system.
AB  - The baculovirus expression vector system (BEVS) is a powerful and versatile
      system for protein expression, which has many advantages. However, a limitation
      of any lytic viral expression system, including BEVS, is that death and lysis of
      infected insect cells terminates protein production. This results in interruption
      of protein production and higher production costs due to the need to set up new
      infections, maintain uninfected cells, and produce pure viral stocks. Genetic
      methods to slow or prevent cell death while maintaining high-level, virus-driven
      protein production could dramatically increase protein yields. Several approaches
      have been used to improve the BEVS and increase the synthesis of functional
      proteins. Successful enhancement of the BEVS was obtained when various gene
      elements were added to the virus, secretion and posttranslational processing were
      modified, or protein integrity was improved. A gene family from the insect virus
      Campoletis sonorensis ichnovirus (CsIV) was discovered that delays lysis of
      baculovirus-infected cells, thereby significantly enhancing recombinant protein
      production in the BEVS system. By using the CsIV vankyrin gene family, protein
      production in the vankyrin-enhanced BEVS (VE-BEVS) was increased by a factor of 4
      to 15-fold by either coexpressing the vankyrin protein from a dual BEVS or by
      providing its activity in trans by expressing the vankyrin protein from a stably
      transformed cell line. In sum, VE-BEVS is an enhancement of the existing BEVS
      technology that markedly improves protein expression levels while reducing the
      cost of labor and materials.

PMID- 16997010
TI  - Baculovirus display: a multifunctional technology for gene delivery and
      eukaryotic library development.
AB  - For over a decade, phage display has proven to be of immense value, allowing
      selection of a large variety of genes with novel functions from diverse
      libraries. However, the folding and modification requirements of complex proteins
      place a severe constraint on the type of protein that can be successfully
      displayed using this strategy, a restriction that could be resolved by similarly
      engineering a eukaryotic virus for display purposes. The quite recently
      established eukaryotic molecular biology tool, the baculovirus display vector
      system (BDVS), allows combination of genotype with phenotype and thereby enables
      presentation of eukaryotic proteins on the viral envelope or capsid. Data have
      shown that the baculovirus, Autographa californica multiple nucleopolyhedrovirus
      (AcMNPV), is a versatile tool for eukaryotic virus display. Insertion of
      heterologous peptides and/or proteins into the viral surface by utilizing the
      major envelope glycoprotein gp64, or foreign membrane-derived counterparts,
      allows incorporation of the sequence of interest onto the surface of infected
      cells and virus particles. A number of strategies are being investigated in order
      to further develop the display capabilities of AcMNPV and improve the complexity
      of a library that may be accommodated. Numerous expression vectors for various
      approaches of surface display have already been developed. Further improvement of
      both insertion and selection strategies toward development of a refined tool for
      use in the creation of useful eukaryotic libraries is, however, needed. Here, the
      status of baculovirus display with respect to alteration of virus tropism,
      antigen presentation, transgene expression in mammalian cells, and development of
      eukaryotic libraries will be reviewed.

PMID- 16997011
TI  - Stably transformed insect cell lines: tools for expression of secreted and
      membrane-anchored proteins and high-throughput screening platforms for drug and
      insecticide discovery.
AB  - Insect cell-based expression systems are prominent amongst current expression
      platforms for their ability to express virtually all types of heterologous
      recombinant proteins. Stably transformed insect cell lines represent an
      attractive alternative to the baculovirus expression system, particularly for the
      production of secreted and membrane-anchored proteins. For this reason,
      transformed insect cell systems are receiving increased attention from the
      research community and the biotechnology industry. In this article, we review
      recent developments in the field of insect cell-based expression from two main
      perspectives, the production of secreted and membrane-anchored proteins and the
      establishment of novel methodological tools for the identification of bioactive
      compounds that can be used as research reagents and leads for new pharmaceuticals
      and insecticides.

PMID- 16997012
TI  - Protein N-glycosylation in the baculovirus-insect cell expression system and
      engineering of insect cells to produce "mammalianized" recombinant glycoproteins.
AB  - Baculovirus expression vectors are frequently used to express glycoproteins, a
      subclass of proteins that includes many products with therapeutic value. The
      insect cells that serve as hosts for baculovirus vector infection are capable of
      transferring oligosaccharide side chains (glycans) to the same sites in
      recombinant proteins as those that are used for native protein N-glycosylation in
      mammalian cells. However, while mammalian cells produce compositionally more
      complex N-glycans containing terminal sialic acids, insect cells mostly produce
      simpler N-glycans with terminal mannose residues. This structural difference
      between insect and mammalian N-glycans compromises the in vivo bioactivity of
      glycoproteins and can potentially induce allergenic reactions in humans. These
      features obviously compromise the biomedical value of recombinant glycoproteins
      produced in the baculovirus expression vector system. Thus, much effort has been
      expended to characterize the potential and limits of N-glycosylation in insect
      cell systems. Discoveries from this research have led to the engineering of
      insect N-glycosylation pathways for assembly of mammalian-style glycans on
      baculovirus-expressed glycoproteins. This chapter summarizes our knowledge of
      insect N-glycosylation pathways and describes efforts to engineer baculovirus
      vectors and insect cell lines to overcome the limits of insect cell
      glycosylation. In addition, we consider other possible strategies for improving
      glycosylation in insect cells.

PMID- 16997013
TI  - Vaccines for viral and parasitic diseases produced with baculovirus vectors.
AB  - The baculovirus-insect cell expression system is an approved system for the
      production of viral antigens with vaccine potential for humans and animals and
      has been used for production of subunit vaccines against parasitic diseases as
      well. Many candidate subunit vaccines have been expressed in this system and
      immunization commonly led to protective immunity against pathogen challenge. The
      first vaccines produced in insect cells for animal use are now on the market.
      This chapter deals with the tailoring of the baculovirus-insect cell expression
      system for vaccine production in terms of expression levels, integrity and
      immunogenicity of recombinant proteins, and baculovirus genome stability. Various
      expression strategies are discussed including chimeric, virus-like particles,
      baculovirus display of foreign antigens on budded virions or in occlusion bodies,
      and specialized baculovirus vectors with mammalian promoters that express the
      antigen in the immunized individual. A historical overview shows the wide variety
      of viral (glyco)proteins that have successfully been expressed in this system for
      vaccine purposes. The potential of this expression system for antiparasite
      vaccines is illustrated. The combination of subunit vaccines and marker tests,
      both based on antigens expressed in insect cells, provides a powerful tool to
      combat disease and to monitor infectious agents.

PMID- 16997014
TI  - Baculoviruses and mammalian cell-based assays for drug screening.

PMID- 16997015
TI  - Baculovirus vectors for gene therapy.
AB  - Since the discovery that baculoviruses can efficiently transduce mammalian cells,
      baculoviruses have been extensively studied as potential vectors for both in
      vitro and in vivo gene therapy. This chapter reviews the history of this research
      area, cells permissive to baculovirus transduction, factors influencing
      transduction and transgene expression, efforts to improve transduction,
      mechanisms of virus entry and intracellular trafficking, applications for in vivo
      and ex vivo gene therapy, as well as advantages, limitations, and safety issues
      concerning use of baculoviruses as gene therapy vectors. Recent progress and
      efforts directed toward overcoming existing bottlenecks are emphasized.

PMID- 16997016
TI  - Genetically modified baculoviruses: a historical overview and future outlook.
AB  - The concept of using genetic engineering to improve the natural insecticidal
      activity of baculoviruses emerged during the 1980s. Both academic and industrial
      laboratories have since invested a great deal of effort to generate genetically
      modified (GM) or recombinant baculoviruses with dramatically improved speeds of
      kill. Optimal production methodologies and formulations have also been developed,
      and the safety and ecology of the recombinant baculoviruses have been thoroughly
      investigated. Unfortunately, the initial excitement that was generated by these
      technologies was tempered when industry made a critical decision to not complete
      the registration process of GM baculoviruses for pest insect control. In this
      chapter, we summarize the developments in the field from a historical perspective
      and provide our opinions as to the current status and future potential of the
      technology. We will argue that GM baculoviruses are valuable and viable tools for
      pest insect control both alone and in combination with wild-type viruses. We
      believe that these highly effective biopesticides still have a bright future in
      modern agriculture as public awareness and acceptance of GM organisms, including
      GM baculoviruses, increases.

PMID- 16997017
TI  - Densoviruses for control and genetic manipulation of mosquitoes.
AB  - Mosquito densoviruses (MDV) are parvoviruses that replicate in the nuclei of
      mosquito cells and cause the characteristic nuclear hypertrophy (densonucleosis)
      that gives them their name. Several MDV that differ in pathogenicity both in
      vitro and in vivo have been isolated. MDV have a number of features that make
      them potentially attractive as biological control agents for mosquito-borne
      disease. They are nonenveloped and relatively stable in the environment. They are
      highly specific for mosquitoes and they infect and kill larvae in a dose
      dependent manner in the aqueous larval habitat. Infected larvae that survive to
      become adult mosquitoes exhibit a dose-dependent shortening of lifespan and many
      do not survive longer than the extrinsic incubation period for arboviruses. Thus
      they may have a significant impact on transmission of pathogens. Infected females
      can transmit the virus vertically by laying infected eggs in new oviposition
      sites. Studies on how MDV affect populations are relatively limited. Population
      cage studies suggest that they will persist and spread in populations and limited
      field studies have shown similar preimaginal mortality in wild populations to
      that seen in laboratory studies. The availability of infectious clones of MDV
      genomes allows the development of densovirus vectors for expressing genes of
      interest in mosquito cells and mosquitoes. Recently short hairpin RNA expression
      cassettes that induce RNA interference have been inserted into densovirus
      genomes. These expression cassettes should be useful for both research and
      disease-control applications.

PMID- 16997018
TI  - Potential uses of Cys-motif and other polydnavirus genes in biotechnology.
AB  - Exploiting the ability of insect pathogens, parasites, and predators to control
      natural and damaging insect populations is a cornerstone of biological control.
      Here we focus on an unusual group of viruses, the polydnaviruses (PDV), which are
      obligate symbionts of some hymenopteran insect parasitoids. PDVs have a variety
      of important pathogenic effects on their parasitized hosts. The genes controlling
      some of these pathogenic effects, such as inhibition of host development,
      induction of precocious metamorphosis, slowed or reduced feeding, and immune
      suppression, may have use for biotechnological applications. In this chapter, we
      consider the physiological functions of both wasp and viral genes with emphasis
      on the Cys-motif gene family and their potential use for insect pest control.

PMID- 16997020
TI  - Small RNA viruses of insects: expression in plants and RNA silencing.
AB  - Interest in insect small RNA viruses (SRVs) has grown slowly but steadily. A
      number of new viruses have been analyzed at the sequence level, adding to our
      knowledge of their diversity at the level of both individual virus species and
      families. In particular, a number of possible new virus families have emerged.
      This research has largely been driven by interest in their potential for pest
      control, as well as in their importance as the causal agents of disease in
      beneficial arthropods. At the same time, research into known viruses has made
      valuable contributions to our understanding of an emerging new field of central
      importance to molecular biology-the existence of RNA-based gene silencing,
      developmental control, and adaptive immune systems in eukaryotes. Subject to RNA
      based adaptive immune responses in their hosts, viruses have evolved a variety of
      genes encoding proteins capable of suppressing the immune response. Such genes
      were first identified in plant viruses, but the first examples known from animal
      viruses were identified in insect RNA viruses. This chapter will address the
      diversity of insect SRVs, and attempts to harness their simplicity in the
      engineering of transgenic plants expressing viruses for resistance to insect
      pests. We also describe RNA interference and antiviral pathways identified in
      plants and animals, how they have led viruses to evolve genes capable of
      suppressing such adaptive immunity, and the problems presented by these pathways
      for the strategy of expressing viruses in transgenic plants. Approaches for
      countering these problems are also discussed.

PMID- 16997019
TI  - Virus-derived genes for insect-resistant transgenic plants.
AB  - Insect viruses have evolved to counter physiological barriers to infection
      presented by the host insect. For the Lepidoptera (butterflies and moths), these
      barriers include (1) the peritrophic membrane (PM) lining the gut, which presents
      a physical barrier to virus infection of the midgut epithelial cells, (2) the
      basement membrane (BM) that overlies the gut thereby restricting secondary
      infection of other tissues, and (3) the immune system of the host insect. Hence,
      insect viruses provide a resource for genes that disrupt host physiology in a
      specific manner, and these genes in turn serve as a resource both for the study
      of physiological processes, and for disruption of these processes for pest
      management purposes. There are several examples of the application of genes used
      by an insect virus to overcome the PM barrier for production of insect-resistant
      transgenic plants. There are other examples of intrahemocoelic effectors, such as
      BM-degrading proteases that can only be used with an appropriate system for
      delivery of the agent from the gut into the hemocoel (body cavity) of the insect
      pest. In this chapter, we describe (1) baculovirus- and entomopoxvirus-derived
      genes that alter the physiology of the host insect, (2) use of these and
      homologous genes for production of insect-resistant transgenic plants, (3) other
      viral genes that have potential for use in development of insect-resistant
      transgenic plants, and (4) the use of plant lectins for delivery of
      intrahemocoelic toxins from transgenic plants. Plant expression of polydnavirus
      derived genes is described by Gill et al. (this volume, pp. 393-426).

PMID- 16997023
TI  - Tobacco control interventions in the emergency department: a joint statement of
      emergency medicine organizations.
AB  - Smoking is the leading cause of preventable death and illness in the United
      States. National practice guidelines call for all health care providers to "ask"
      all patients about tobacco use, and to "advise, assess, assist, arrange" when
      smokers want to quit smoking (the "5 As"). Emergency departments (EDs) have not
      been an important locus of tobacco control efforts, although ED patients
      typically smoke at rates exceeding that of the general population, are interested
      in quitting, and often have limited access to primary care. To address the role
      of emergency medicine in tobacco control, the American College of Emergency
      Physicians convened a task force of representatives of major emergency medicine
      professional organizations. Funded by the Robert Wood Johnson Foundation, the
      group met in 2004 and 2005. This article represents a summary of the task force's
      recommendations for tobacco control practice, training, and research. We call on
      emergency care providers to routinely assess patients' smoking status, offer
      brief advice to quit, and refer patients to the national smokers' Quitline (800
      QUIT-NOW) or a locally available program. Given the global burden of tobacco
      related illness, the task force considers it essential for emergency physicians
      to conduct research into the efficacy of ED-based interventions and to place
      tobacco control into the training curriculum for emergency medicine residencies.
      Tobacco control fits within the traditions of other ED-based public health
      practices, such as injury control. ED-based tobacco control would allow the
      specialty to help fulfill the Healthy People 2010 mandate to reduce the
      prevalence of smoking among US citizens.

PMID- 16997024
TI  - Winging it through research: an innovative approach to a basic understanding of
      research methodology.

PMID- 16997025
TI  - Emergency Nurses Association position statement: collaborative and
      interdisciplinary research.

PMID- 16997026
TI  - TelEmergency: distance emergency care in rural emergency departments using nurse
      practitioners.

PMID- 16997027
TI  - Emergency preparedness and bioterrorism: a survey of the Nebraska Medical Center
      staff and physicians.

PMID- 16997028
TI  - Someone watching over me: observations in pediatric triage.

PMID- 16997029
TI  - Recombinant factor VIIa and the trauma patient.

PMID- 16997030
TI  - Carbon monoxide poisoning following a natural disaster: a report on Hurricane
      Rita.

PMID- 16997031
TI  - A 44-year-old pregnant patient who had and needed HELLP.

PMID- 16997033
TI  - Hyperbaric oxygen therapy.

PMID- 16997034
TI  - Nuclear stress testing in an emergency department observation unit.

PMID- 16997035
TI  - An informal discussion of emergency nurses' current clinical practice: what's new
      and what works.

PMID- 16997036
TI  - The risks associated with the use of multidose vials.

PMID- 16997037
TI  - What is your level of readiness?

PMID- 16997038
TI  - Cops and Docs: St Clare Hospital's strategy for educating teens about the medical
      and legal consequences of violence.

PMID- 16997040
TI  - Self-cutting behaviors in adolescents.

PMID- 16997041
TI  - Inhalant abuse.

PMID- 16997042
TI  - Federal Drug Administration authority and the emergency nurse: implications for
      patient safety.

PMID- 16997043
TI  - Posterior hip dislocation with femoral head fracture: an unusual injury.

PMID- 16997045
TI  - Chryseobacterium meningosepticum infection and cardiac tamponade in a long-term
      hemodialysis patient.
AB  - Chryseobacterium meningosepticum is a lactose-nonfermenting gram-negative bacilli
      ubiquitously found in the natural and hospital environment. Clinical infection
      caused by C. meningosepticum is very rare among healthy adults. We present the
      case of a patient with end-stage renal disease who developed purulent
      pericarditis with C. meningosepticum infection, which rapidly evolved into
      cardiac tamponade and death. To our knowledge, this is the first case in which C.
      meningosepticum caused fatal purulent pericarditis in a hemodialysis patient.

PMID- 16997046
TI  - The uncertain significance of anti-glomerular basement membrane antibody among
      HIV-infected persons with kidney disease.
AB  - Glomerular lesions that complicate patients with human immunodeficiency virus
      (HIV) infection include HIV-associated nephropathy, membranous glomerulopathy,
      and immune-complex glomerulonephritides. This case series presents 3 patients
      with clinically significant renal disease and positive test results for anti
      glomerular basement membrane (anti-GBM) antigen. Characteristic histological
      findings that would suggest anti-GBM antibodies have a significant role in the
      pathological state of each patient's kidney disease were absent. In addition,
      each patient recovered without specific treatment for anti-GBM disease. This case
      series suggests that anti-GBM antibodies likely are related to the B-cell
      expansion previously described in patients with HIV infection. We propose that
      clinicians interpret results of anti-GBM antibody tests carefully for patients
      with HIV infection, considering biopsy before empiric therapy, particularly in a
      clinical presentation that is atypical for Goodpasture disease.

PMID- 16997047
TI  - Recurrent hyponatremia associated with citalopram and mirtazapine.
AB  - Depression is a common problem in elderly patients and frequently is treated with
      antidepressants. We present the case of a 67-year-old depressed woman who began
      treatment with citalopram. Two months later, hyponatremia was diagnosed, most
      likely syndrome of inappropriate antidiuretic hormone secretion. After
      discontinuation of citalopram therapy, serum sodium concentrations normalized.
      Later, she began treatment with mirtazapine. Five months after initiating
      mirtazapine therapy, she developed symptomatic hyponatremia. After mirtazapine
      therapy was discontinued, serum sodium concentrations normalized. In this case,
      unlike those previously reported, hyponatremia recurred 5 months after switching
      from citalopram to mirtazapine, which is believed to be a safe antidepressant. In
      conclusion, patients older than 60 years should have baseline electrolyte
      measurements before starting therapy with an antidepressant, and these should be
      monitored not only in the first weeks of treatment, but throughout the full
      course.

PMID- 16997048
TI  - Anemia after renal transplantation.
AB  - Anemia in the setting of chronic kidney disease is a well-recognized phenomenon
      that is associated with decreasing renal function and deficiency of or resistance
      to erythropoietin. However, anemia in the post-renal transplantation setting has
      received comparatively less attention in the literature. In this review, we aim
      critically to appraise the available literature regarding posttransplantation
      anemia, concentrating in particular on the prevalence of posttransplantation
      anemia, its etiopathogenesis, potential effects on morbidity and mortality, and
      the rationale for intervention and treatment. Despite deficiencies in the
      literature, we conclude that posttransplantation anemia is a common phenomenon
      that can occur either early or late posttransplantation, and its causation is
      usually multifactorial and includes contributions notably from poor or decreasing
      renal function, immunosuppression, and iron deficiency. Conversely, there is a
      shortage of well-conducted prospective studies looking at the morbidity
      attributable to posttransplantation anemia and a lack of trial evidence to
      determine whether intervention improves patient morbidity and outcome.

PMID- 16997049
TI  - The epidemiology of hemoglobin levels in patients with type 2 diabetes.
AB  - BACKGROUND: Anemia is a common finding in patients with diabetes, for whom it
      constitutes an additional burden. The aim of this study is to clarify the natural
      history of anemia in patients with type 2 diabetes and describe factors that
      predict a decrease in hemoglobin (Hb) levels. METHODS: A 5-year prospective
      cohort study was designed as a follow-up of 503 individuals with type 2 diabetes
      in a single diabetes clinic. In addition to standard management, a full blood
      count was obtained at each routine visit. No intervention was undertaken to
      modify Hb levels. RESULTS: At baseline, 12% of patients had anemia, and an
      additional 13% developed anemia during follow-up. Overall Hb levels decreased by 
      0.07 +/- 0.01 g/dL/y, suggesting that anemia is the end point of a process that
      begins more than 10 years previously with the initiation of vascular damage. The
      greatest decreases in Hb levels were seen in patients with macroalbuminuria,
      renal impairment, or established macrovascular disease at baseline (all P <
      0.01). In patients with microvascular disease, decreasing Hb levels tracked with
      decreasing glomerular filtration rates (GFRs). Patients with an estimated GFR
      greater than 90 mL/min/1.73 m2 (>1.5 mL/s) or normoalbuminuria had stable Hb
      levels during the 5-year follow-up. In patients with anemia in our cohort who
      were managed conservatively, Hb levels decreased by 0.09 +/- 0.03 g/dL/y. This
      decrease was associated with HbA1c levels, but not renal function. CONCLUSION:
      This study defines the natural history of Hb levels in patients with type 2
      diabetes. Early identification of anemia may be achieved by means of annual or
      biannual screening in high-risk groups with nephropathy, advanced age, or
      macrovascular disease. These data are important for developing a rational
      response to the prevention and management of anemia.

PMID- 16997050
TI  - Causes of hypocitraturia in recurrent calcium stone formers: focusing on urinary
      potassium excretion.
AB  - BACKGROUND: Multiple factors associated with hypocitraturia have been identified.
      However, limited studies addressing the causal relationship to hypocitraturia are
      available. We therefore conducted this study to determine factors associated with
      hypocitraturia and show their causal relationship in recurrent calcium stone
      formers. METHODS: Dietary review and 24-hour urine samples were obtained from all
      recurrent calcium stone formers referred for metabolic workup in the stone
      clinic. One month of oral potassium chloride supplementation was prescribed to
      stone formers to determine the causal relationship between urinary potassium and
      citrate levels. RESULTS: Eighty-three subjects, 44 men and 39 women, were
      recruited to participate in this study. Hypocitraturia (citrate < 300 mg/d [<1.43
      mmol/d]) was found in 50.6% of subjects. Four independent urinary variables
      associated with hypocitraturia were identified, including potassium level, net
      gastrointestinal alkaline absorption, calcium level, and titratable acid. Urinary
      potassium level was the strongest predictor of urinary citrate level.
      Hypocitraturic subjects also had lower fruit intake compared with subjects with
      high urinary citrate levels. Potassium chloride supplementation to a subgroup of
      this population (n = 58) resulted in a significant increase in urinary citrate
      excretion (350.73 +/- 27.25 versus 304.15 +/- 30.00 mg/d [1.67 +/- 0.13 versus
      1.45 +/- 0.14 mmol/d]; P < 0.02), but no alteration in fractional excretion of
      citrate (19.7% +/- 2.7% versus 23.1% +/- 2.4%; P > 0.05). CONCLUSION:
      Hypocitraturia was found to be a common risk factor associated with recurrent
      calcium stone formation and low urinary potassium level, low alkaline absorption,
      low urinary calcium level, and high titratable acid excretion. Hypocitraturia is
      predominantly of dietary origin. Estimation of fruit intake should be included in
      the metabolic evaluation for recurrent calcium stone formation.

PMID- 16997051
TI  - Biochemical and stone-risk profiles with topiramate treatment.
AB  - BACKGROUND: Topiramate is a novel neuromodulatory agent commonly prescribed for
      the treatment of seizure disorders and for migraine headache prophylaxis. Calcium
      phosphate kidney stones have been observed with topiramate treatment, but a
      comprehensive elucidation of stone-risk profile was not reported previously. This
      study explores the relationship between topiramate treatment and propensity for
      kidney stone formation. METHODS: Thirty-two topiramate-treated subjects and 50
      healthy volunteers participated in a cross-sectional study in which serum
      chemistry test and 24-hour urine collection results were evaluated for stone
      risk. Furthermore, a short-term longitudinal study was conducted in 7 patients to
      assess stone risk before and 3 months after topiramate treatment. RESULTS: Serum
      bicarbonate levels were lower with topiramate treatment. Urinary pH, urinary
      bicarbonate excretion, and fractional excretion of bicarbonate increased, whereas
      urinary citrate excretion was significantly lower (737 +/- 329 versus 278 +/- 226
      mg/d; P < 0.001). Net acid excretion did not change. The relative saturation
      ratio for brushite increased with topiramate treatment (3.14 +/- 1.69 versus 1.27
      +/- 1.26; P < 0.001) because of urinary alkalinization and decreased urinary
      citrate levels. Urinary saturation of undissociated uric acid decreased (41 +/-
      52 versus 76 +/- 60 mg/d; P < 0.001). CONCLUSION: Treatment with topiramate
      causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and
      increased urinary pH. These changes increase the propensity to form calcium
      phosphate stones.

PMID- 16997052
TI  - Circulating endothelial cells as a prognostic marker in thrombotic
      microangiopathy.
AB  - BACKGROUND: Circulating endothelial cells (CECs) are a reliable marker of disease
      activity in a variety of vascular disorders. Damage to microvascular endothelial
      cells is a hallmark of thrombotic microangiopathy (TMA). The aim of this study is
      to identify and count CECs during the course of TMA and evaluate whether cell
      numbers may serve as a prognostic marker in patients undergoing plasma exchange.
      METHODS: Fifteen patients (8 women, 7 men) aged 31 to 66 years with TMA of
      different causes were studied before and after 4 sessions of plasma exchange.
      CECs were isolated by using anti-CD146-driven immunomagnetic isolation and
      counted after staining with Ulex Europaeus lectin-1. RESULTS: Numbers of CECs
      were markedly elevated in all patients before treatment (64 to 672 CEC/mL; mean,
      320 +/- 205 CEC/mL) compared with healthy controls (0 to 16 CEC/mL; mean, 6.4 +/-
      4.2 CEC/mL; P < 0.001). Patients with a favorable outcome had significantly
      greater initial CEC levels (mean, 426 +/- 175 CEC/mL; P < 0.001), and cell
      numbers decreased significantly after 4 treatments of plasma exchange (mean, 101
      +/- 53 CEC/mL; P = 0.001). Patients with disease unresponsive to plasma exchange
      presented with lower initial CEC levels (mean, 108 +/- 36 CEC/mL), and numbers
      failed to decrease after plasma exchange (mean, 114 +/- 57 CEC/mL; P = 0.827).
      CONCLUSION: Markedly elevated numbers of CECs reflect severe and widespread
      endothelial damage in patients with TMA. Cell numbers at presentation and their
      degree of decrease after 4 sessions of plasma exchange could provide important
      prognostic clues.

PMID- 16997053
TI  - The advanced glycation end product N(epsilon)-carboxymethyllysine is not a
      predictor of cardiovascular events and renal outcomes in patients with type 2
      diabetic kidney disease and hypertension.
AB  - BACKGROUND: Advanced glycation end products (AGEs) are implicated in the
      pathogenesis of vascular damage, especially in patients with diabetes and renal
      insufficiency. The oxidatively formed AGE N(epsilon)-carboxymethyllysine (CML) is
      thought to be a marker of oxidative stress. METHODS: Four hundred fifty patients
      with type 2 diabetes and nephropathy from the Irbesartan in Diabetic Nephropathy
      Trial cohort (mean age, 58 +/- 8.2 years; 137 women, 313 men) with a mean
      glomerular filtration rate of 48.2 mL/min (0.80 mL/s; Modification of Diet in
      Renal Disease formula) were followed up for 2.6 years. Serum CML was measured by
      using an enzyme-linked immunosorbent assay. Relationships between CML levels,
      traditional risk factors, and cardiovascular and renal events were tested in Cox
      proportional hazards models. RESULTS: Mean serum CML level was 599.9 +/- 276.0
      ng/mL, and mean hemoglobin A1c level was 7.5% +/- 1.6%. One hundred forty-three
      first cardiovascular events occurred during follow-up; 74 patients died, 44 of
      cardiovascular causes. Final multivariate analysis showed age (relative risk
      [RR], 1.87; confidence interval [CI], 1.13 to 3.11; P = 0.016 for the highest
      compared with lowest quartile), history of prior cardiovascular events (RR, 1.96;
      CI, 1.35 to 2.85; P < 0.0005), and 24-hour urinary albumin-creatinine ratio (RR,
      1.29; CI, 1.11 to 1.50 per doubling; P < 0.0005) to be independent risk factors
      for a first cardiovascular event, but not CML level. CML level also did not
      correlate significantly with renal outcome. CONCLUSION: Serum CML level could not
      be identified as an independent risk factor for cardiovascular or renal outcomes
      in the examined population. This suggests that traditional risk factors might
      have a more important role for these end points or that other AGE compounds, as
      well as tissue AGE levels, might be of greater relevance compared with serum
      levels, which remains open to further study.

PMID- 16997054
TI  - Predictive value of a positive fecal occult blood test increases as the severity
      of CKD worsens.
AB  - BACKGROUND: Because chronic kidney disease (CKD) may be associated with
      gastrointestinal bleeding from trivial mucosal lesions, we hypothesized that the
      predictive value of a positive fecal occult blood test (FOBT) result for
      clinically important colonic lesions would decrease as the stage of CKD worsened.
      METHODS: We prospectively identified 1,225 consecutive asymptomatic average-risk
      patients who were referred for colonoscopy to evaluate a positive FOBT result.
      Using the Modification of Diet in Renal Disease equation, we estimated glomerular
      filtration rate (GFR) and staged the severity of CKD by using standard criteria
      as follows: normal/stage 1 (GFR > or = 90 mL/min/1.73 m2 [> or = 1.50 mL/s]),
      stage 2/3 (GFR 30 to 89 mL/min/1.73 m2 [0.50 to 1.48 mL/s]), and stage 4/5 (GFR <
      30 mL/min/1.73 m2 [< 0.50 mL/s] or dialysis). RESULTS: Clinically important
      lesions were identified in 23.9% of 531 individuals with none/stage 1 CKD, 32.8%
      of 497 subjects with stage 2/3 CKD, and 42.6% of 197 patients with stage 4/5 CKD
      (P < 0.001). Compared with patients with none/stage 1 CKD, adjusted odds of
      identifying a clinically important lesion were 1.61 (95% confidence interval,
      1.21 to 2.15) in subjects with stage 2/3 CKD and 2.33 (95% confidence interval,
      1.62 to 3.36) in patients with stage 4/5 CKD. Prevalences of adenomas of 1 cm or
      greater (15.1% versus 20.1% versus 22.8%; P = 0.007), carcinomas (5.1% versus
      10.1% versus 13.2%; P < 0.001), and vascular ectasias (1.7% versus 2.4% versus
      6.1%; P = 0.003) increased with the severity of CKD. CONCLUSION: Contrary to our
      initial hypothesis, we found that the predictive value of a positive FOBT result
      for clinically important colonic lesions increased as the severity of CKD
      worsened.

PMID- 16997055
TI  - An interventional controlled trial comparing 2 management models for the
      treatment of tunneled cuffed catheter bacteremia: a collaborative team model
      versus usual physician-managed care.
AB  - BACKGROUND: The management of tunneled cuffed catheter (TCC)-associated
      bacteremias varies among nephrologists. To determine whether patient outcomes
      after TCC-associated bacteremia can be improved by modifying the management
      model, we performed an interventional controlled trial comparing a collaborative
      team model, intervention (INT), with the usual physician-managed model, usual
      care (UC). METHODS: INT consisted of an infection manager who worked closely with
      nephrologists and dialysis staff and made treatment recommendations using the
      available published guidelines at the time of the study's conception (Dialysis
      Outcomes Quality Initiative guideline no. 26, 1997) and additional literature
      based recommendations. Nephrologists made the final treatment decisions. TCC
      associated bacteremia was physician managed in the UC group. RESULTS: Two hundred
      twenty-three episodes of TCC-associated bacteremia occurred in 7 outpatient
      hemodialysis units during the 2-year study period. The INT was associated with a
      significantly lower incidence of recurrent bacteremia with the same organism
      (INT, 6% versus UC, 18%; odds ratio, 0.28; 95% confidence interval, 0.09 to 0.8;
      P = 0.015) and death from sepsis (INT, 0% versus UC, 6%; P < 0.02). In INT units,
      there was a 45% decrease in the practice of TCC salvage (TCC not removed; P =
      0.05). Antibiotic prescribing practices (final antibiotic selection, dose, and
      duration of therapy) were improved in INT units compared with UC units. By using
      multivariate analysis, the INT was associated with a 73% decrease in the combined
      outcome of recurrent bacteremia or septic death (P < 0.02). CONCLUSION:
      Implementation of a collaborative team model for the management of TCC-associated
      bacteremic episodes is associated with improvement in the quality of heath care
      delivery and patient outcomes.

PMID- 16997056
TI  - Comparison of low-dose gentamicin with minocycline as catheter lock solutions in
      the prevention of catheter-related bacteremia.
AB  - BACKGROUND: Catheter-restricted antibiotic lock solutions were found to be
      effective in the prevention of catheter-related bacteremia (CRB), but
      insufficient data are available about the ideal agent and dose. We hypothesized
      that a low concentration of gentamicin would be as effective as the high doses
      studied in the past. METHODS: In this prospective, open-labeled, randomized,
      clinical trial of patients on long-term hemodialysis therapy, patients were
      randomly assigned to administration of an antibiotic lock solution of
      gentamicin/citrate (4 mg/mL), minocycline/EDTA, or the control solution of
      heparin. Patients were followed up until the study end point of CRB was reached
      or a censoring event occurred. Interim data analysis was performed after 6 months
      to assess data safety; efficacy was noted and the study was terminated early.
      RESULTS: Sixty-two patients were enrolled into the study, evenly distributed in 3
      arms, with data from 1 patient excluded from analysis. Seven of 20 patients in
      the heparin group (4.0 events/1,000 catheter days), 1 of 21 patients in the
      minocycline group (0.4 events/1,000 catheter days), and none of 20 patients in
      the gentamicin group developed bacteremia. Results were statistically significant
      by using 2-tailed Fisher exact test; heparin versus gentamicin, P = 0.008, and
      heparin versus minocycline, P = 0.020. CONCLUSION: Antibiotic lock solutions are
      superior to the standard heparin lock alone in the prevention of CRBs, and low
      dose gentamicin solution has efficacy similar to that of greater concentrations
      used in previous studies.

PMID- 16997057
TI  - The epidemiology of systolic blood pressure and death risk in hemodialysis
      patients.
AB  - BACKGROUND: This study compares the associations of predialysis systolic blood
      pressure (SBP) with mortality risk in both incident and prevalent hemodialysis
      (HD) cohorts by using both conventional and time-varying Cox analyses, thus
      addressing limitations of prior studies. METHODS: A total of 56,338 incident
      patients starting HD therapy during 1997 to 2001 and 69,590 prevalent HD patients
      on January 1, 2002, were grouped into the following categories: (1) SBP less than
      120 mm Hg, (2) 120 < or = SBP < 140 mm Hg, (3) 140 < or = SBP < 160 mm Hg, (4)
      160 < or = SBP < 180 mm Hg, (5) 180 < or = SBP < 200 mm Hg, and (6) SBP of 200 mm
      Hg or greater. Conventional and time-varying models evaluated 1-year and 3-year
      (incident patients only) survival. RESULTS: Nine percent and 26.0% of incident
      patients and 5.7% and 20.1% of prevalent patients were in categories 1 and 2,
      respectively. Their associated 1-year hazard ratios (HRs) were 2.63 to 3.68 and
      1.57 to 1.68 compared with category 4, the reference group. HRs for categories 3,
      5, and 6 were not different from category 4. Time-varying models magnified
      category 1 and 2 HRs to 5.54 to 7.42 and 1.92 to 2.21, such that 25% to 35% of
      patients in the target SBP range (< 140 mm Hg) had the greatest risk. A "reversed
      J-shaped" risk profile emerged in the time-varying models, with very high SBP
      (category 6) associated with HRs of 1.52 to 1.55, but only 1% of patients were in
      category 6. Three-year outcomes were similar. CONCLUSION: Epidemiological
      characteristics of predialysis SBP consistently differ from those in the general
      population despite different analytic perspectives. The data suggest a need for
      greater investigative, diagnostic, and therapeutic focus on HD patients with
      normal and prehypertensive blood pressure ranges.

PMID- 16997058
TI  - Hemodialysis modulates gene expression profile in skeletal muscle.
AB  - BACKGROUND: Uremia alters diverse metabolic pathways involving multiple organ
      systems, including skeletal muscle. Skeletal muscle has an important role in
      nutrition, metabolism, oxidative stress, and inflammation. We hypothesized that
      hemodialysis (HD) will change the genomic fingerprinting associated with uremia
      and facilitate expression of a distinct set of genes. METHODS: Five patients with
      end-stage renal disease (ESRD) were studied. Skeletal muscle biopsy specimens
      from the vastus lateralis were obtained before (pre-HD) and during the last 10
      minutes of HD (post-HD). Oligonucleotide microarray (version 2, GeneChip arrays;
      Affymetrix U95A, Santa Clara, CA) was used to analyze global transcriptional
      modification in skeletal muscle by HD. Pre-HD data were compared with data from 3
      subjects without renal failure. RESULTS: In skeletal muscle of patients with
      ESRD, 83 genes were upregulated and 8 genes were downregulated pre-HD compared
      with controls. Pathway analysis linked 55 genes to 5 gene networks involved in
      the regulation of cell cycle, cell proliferation, cellular organization,
      apoptosis, and inflammation. During HD, expression of 22 genes increased and 1
      (TOB1) decreased. Pathway analysis mapped 20 genes to 2 genetic networks involved
      in: (1) inflammation, cell proliferation, and cell signaling; and (2) apoptosis,
      cell function, protein synthesis, and tissue morphology. Reverse-transcription
      polymerase chain reaction confirmed increased expression of GADD45A, BTG2, PDE4B,
      and CEBPD and downregulation of TOB1 in skeletal muscle intradialysis.
      CONCLUSION: In response to the uremic milieu, skeletal muscle goes through very
      active transcriptional and translational changes. HD activates a diverse, yet
      biologically linked, network of genes related to inflammation and apoptosis in
      skeletal muscle.

PMID- 16997059
TI  - Epidemiology of hepatitis C virus among long-term dialysis patients: a 9-year
      study in an Italian region.
AB  - BACKGROUND: Monitoring hepatitis C virus (HCV) antibodies (anti-HCV) in long-term
      dialysis patients is an important issue of public health. The aim of the study is
      to analyze the prevalence, seroconversion rate, and impact of HCV-positive
      serological test results on survival. METHODS: We studied 6,412 patients starting
      long-term dialysis therapy reported to Lazio Dialysis Registry (Italy) between
      1995 and 2003. HCV serological status was assessed by using second- or third
      generation assays. Patients who were seronegative at the beginning of a period
      who became seropositive at the end of the same period are defined as
      seroconverters. RESULTS: In 1995 to 2003, the overall prevalence of anti-HCV
      among long-term dialysis patients decreased from 30.6% to 15.1%; we did not
      observe a decrease in prevalence of anti-HCV in those starting dialysis
      treatment. After a decrease in the first year, HCV seroconversion rates remained
      stable at approximately 2 cases/100 person-years. Survival at 9 years was lower
      for both HCV seroconverters and those already anti-HCV positive at dialysis
      therapy initiation compared with HCV-negative subjects (log-rank test, P <
      0.001). Results of a multiple Cox model showed that subjects who were or became
      anti-HCV positive had a hazard ratio of 1.29 (95% confidence interval, 1.15 to
      1.44) compared with HCV-negative patients. CONCLUSION: We did not observe a
      significant decrease in HCV seroconversion rates in 1995 to 2003. The overall
      decrease in anti-HCV prevalence could be related to the lower survival
      probability for both HCV seroconverters and those already HCV positive at long
      term dialysis therapy initiation compared with HCV-negative subjects. Our
      findings confirm that additional efforts should be made to minimize the risk for
      HCV infection before and during long-term dialysis treatment.

PMID- 16997060
TI  - Sestamibi scintigraphy, topography, and histopathology of parathyroid glands in
      secondary hyperparathyroidism.
AB  - BACKGROUND: Several imaging techniques presently are available to assess the
      location of hyperplastic parathyroid glands. The purpose of the present study is
      to assess the place of dual-phase technetium Tc 99m-sestamibi (MIBI) scintigraphy
      in the preoperative localization of hyperplastic parathyroid glands in patients
      with severe secondary hyperparathyroidism (SHPT). METHODS: We studied 35
      consecutive adult white hemodialysis patients undergoing a first
      parathyroidectomy after performing MIBI scintigraphy. Hyperplasia of the
      parathyroid glands was classified as diffuse (DH) or nodular (NH). Statistical
      analysis was conducted by comparing patients with MIBI-negative (no focal area of
      increased uptake) with MIBI-positive (> or = 1 focal area of increased uptake)
      results and stratifying parathyroid glands according to location (superior and
      inferior). RESULTS: MIBI scintigraphy showed focal areas of increased uptake in
      at least 1 gland in 25 patients (71.4%). Total number of focal areas of increased
      uptake was 42 of 121 glands removed (sensitivity, 34.7%; specificity, 100%). One
      hundred one glands showed NH and 20 glands showed DH. The 25 patients with MIBI
      positive results had 85 pathological glands removed, and the 10 patients with
      MIBI-negative results had 36 pathological glands removed: in the former, most
      glands showed NH (77 of 85 glands; 90.6%), and in the latter, 24 of 36 glands
      showed NH (66.7%; P = 0.004 at chi-square test). The sensitivity of MIBI
      scintigraphy for distinguishing specific subtypes of hyperplasia was 37.6% (38 of
      101 glands) for NH and 20.0% (4 of 20 glands) for DH (P = 0.0005). The following
      values were significantly greater in inferior compared with superior glands: (1)
      estimated weight (2.1 +/- 0.8 versus 1.6 +/- 1.2 g; P = 0.04), (2) percentage of
      MIBI positivity (34 of 42 inferior glands [80.9%] versus 8 of 42 superior glands
      [19.1%]; P = 0.0001), and (3) percentage of localization permitted by MIBI
      scintigraphy (34 of 63 inferior glands [54.0%] versus 8 of 58 superior glands
      [13.8%]; P = 0.0001). Thus, NH, although equally distributed between inferior (53
      of 63 glands) and superior (48 of 58 glands) glands, showed a percentage of MIBI
      positivity significantly greater in inferior (34 of 53 glands [64.1%]) compared
      with superior glands (8 of 48 glands [16.7%]; P = 0.0001). CONCLUSION: MIBI
      scintigraphy did not show high sensitivity in identifying hyperplastic glands,
      although it was able to identify those with NH better than those with DH. Thus,
      MIBI scintigraphy has limited value preoperatively for patients with SHPT.
      Estimated weight, percentage of MIBI positivity, and percentage of localization
      permitted by MIBI scintigraphy were significantly greater in inferior glands.

PMID- 16997061
TI  - Prescription patterns of pharmacological agents for left ventricular systolic
      dysfunction among hemodialysis patients.
AB  - BACKGROUND: Recommendations for the management of left ventricular (LV) systolic
      dysfunction in the general population and patients with end-stage renal disease
      (ESRD) include the use of angiotensin-converting enzyme (ACE) inhibitors and beta
      blockers. Limited data from the literature suggest that these pharmacological
      agents may be underused in patients with ESRD. The goal of this study is to
      describe the use of these medications and investigate barriers to their use in
      dialysis patients. METHODS: We prospectively studied 420 hemodialysis patients.
      Diagnosis of systolic dysfunction was based on echocardiogram results. Use of
      cardiac medication was recorded for all patients with systolic dysfunction, and a
      questionnaire was administered to nephrologists to determine the basis for
      decisions concerning ACE-inhibitors and beta-blockers use/nonuse. RESULTS: Forty
      seven patients (11%) were found to have an LV ejection fraction of 40% or less.
      Of those, 72% were administered a beta-blocker and 36% were administered an ACE
      inhibitor. Only 12 patients (25.5%) were administered a combination of beta
      blocker and ACE inhibitor. Reasons indicated by nephrologists for not prescribing
      these medications were "concern about adverse reactions (eg, hypotension,
      hyperkalemia)" in 88% of cases, "adequate control of symptoms with
      ultrafiltration" in 38%, "unproven benefit" in 25%, and "unfavorable risk-benefit
      ratio" in 17%. Medication costs and concern about patient compliance were not
      identified as significant concerns by physicians. CONCLUSION: Only 25.5% of
      patients with ESRD with LV systolic dysfunction receive appropriate treatment.
      Concern regarding adverse reactions was the most frequent reason indicated by
      nephrologists for not prescribing ACE inhibitors and beta-blockers.

PMID- 16997062
TI  - Percutaneous treatment of dysfunctional Brescia-Cimino fistulae through a radial
      arterial approach.
AB  - BACKGROUND: Dysfunctional Brescia-Cimino fistulae contribute to significant
      morbidity in hemodialysis patients. These fistulae normally are treated through a
      retrograde venous approach. There are no data regarding a transradial approach.
      Furthermore, measurement of pressure reduction in the radial artery appears to be
      useful. METHODS: We retrospectively examined 50 interventions to treat 49
      patients (17 men, 32 women; mean age, 61.8 +/- 10.6 years) with Brescia-Cimino
      fistulae. Inclusion criteria were patients with palpable radial arteries and
      dysfunctional end-to-side Brescia-Cimino fistulae. Patients with infected
      fistulae, contrast allergy, upper-arm/synthetic graft/central-vein stenosis, and
      end-to-end Brescia-Cimino fistulae were excluded from the study. Radial arterial
      pressures before and after angioplasty were compared as a surrogate of stenosis
      relief. Anatomic and clinical success rates were calculated. RESULTS: Sixty-five
      stenoses and 4 total occlusions were treated through radial access. All radial
      punctures were successful, except in 1 patient. Most lesions were located in the
      cephalic vein (87%). Mean length of treated lesions was 4.1 +/- 2.8 cm. Mean
      pretreatment diameter of lesion stenoses was 76.7% +/- 12.1%. Mean posttreatment
      diameter stenosis was 22.6% +/- 8.2% (P < 0.001). Systolic, diastolic, and mean
      blood pressures recorded from the radial artery decreased from 130 +/- 40, 60 +/-
      18, and 87 +/- 27 to 88 +/- 40, 43 +/- 18, and 60 +/- 26 mm Hg (P < 0.001, P <
      0.001, and P < 0.001), respectively. The anatomic success rate of the transradial
      approach was 91.3%. The clinical success rate of the transradial approach was
      96%. CONCLUSION: The transradial approach is a feasible and highly effective
      approach to treat dysfunctional Brescia-Cimino fistulae. Measuring blood pressure
      reduction through the radial artery appears promising as a hemodynamic evaluation
      method.

PMID- 16997063
TI  - A case report comparing various radiological tests in the diagnosis of calcific
      uremic arteriolopathy.
AB  - BACKGROUND: Calcific uremic arteriolopathy (CUA) is a rare necrotizing skin
      condition characterized by calcification in arterioles, leading to ischemia and
      skin ulcerations. This disease affects 1% to 4% of patients with chronic kidney
      disease and has a reported mortality rate up to 80%. The diagnosis of CUA is
      based on clinical judgment suggested by the characteristic skin lesions. Although
      skin biopsy is the gold standard for establishing the diagnosis, it is performed
      infrequently because of poor healing and risk for secondary infections. METHODS:
      In this case report, we compare the ability of various radiological tests to show
      arteriolar calcifications of patients with CUA. Our patient had biopsy-proven CUA
      manifesting as chronic nonhealing ulcers of the calves. She underwent soft-tissue
      x-ray of the affected extremities and high-resolution (0.5-mm slice) computed
      tomographic (CT) scanning with 3-dimensional image reconstruction. We also used a
      dedicated mammography machine to obtain images of the patient's calves. Images
      were compared based on the ability to show small-vessel calcification. RESULTS:
      Plain soft-tissue x-ray showed mildly increased soft-tissue density and very few
      calcified vessels, whereas CT showed few calcified small- and medium-sized
      arterioles. Diffuse calcification of small arterioles in a mesh-like pattern was
      shown by means of the mammography technique. CONCLUSION: Simple, safe, and
      inexpensive x-ray imaging using the mammography technique was superior to plain
      soft-tissue x-ray and 3-dimensional CT in showing the hallmark arteriolar
      calcifications of patients with CUA. Thus, we propose a possible role for this
      technique in diagnosing CUA.

PMID- 16997065
TI  - A 5-year-old girl with impaired renal function after autologous bone marrow
      transplantation.

PMID- 16997066
TI  - Type 2 pseudohypoaldosteronism: new insights into renal potassium, sodium, and
      chloride handling.

PMID- 16997067
TI  - Large-amplitude, spatially correlated fluctuations in BOLD fMRI signals during
      extended rest and early sleep stages.
AB  - A number of recent studies of human brain activity using blood-oxygen-level
      dependent (BOLD) fMRI and EEG have reported the presence of spatiotemporal
      patterns of correlated activity in the absence of external stimuli. Although
      these patterns have been hypothesized to contain important information about
      brain architecture, little is known about their origin or about their
      relationship to active cognitive processes such as conscious awareness and
      monitoring of the environment. In this study, we have investigated the amplitude
      and spatiotemporal characteristics of resting-state activity patterns and their
      dependence on the subjects' alertness. For this purpose, BOLD fMRI was performed
      at 3.0 T on 12 normal subjects using a visual stimulation protocol, followed by a
      27 min rest period, during which subjects were allowed to fall asleep. In
      subjects who were asleep at the end of the scan, we found (a) a higher amplitude
      of BOLD signal fluctuation during rest compared with subjects who were awake at
      the end of the scan; (b) spatially independent patterns of correlated activity
      that involve all of gray matter, including deep brain nuclei; (c) many patterns
      that were consistent across subjects; (d) that average percentage levels of
      fluctuation in visual cortex (VC) and whole brain were higher in subjects who
      were asleep (up to 1.71% and 1.16%, respectively) than in those who were awake
      (up to 1.15% and 0.96%) at the end of the scan and were comparable with those
      levels evoked by intense visual stimulation (up to 1.85% and 0.76% for two
      subject groups); (e) no confirmation of correlation, positive or negative,
      between thalamus and VC found in earlier studies. These findings suggest that
      resting-state activity continues during sleep and does not require active
      cognitive processes or conscious awareness.

PMID- 16997068
TI  - Effects of mild hypoxic hypoxia on poststimulus undershoot of blood-oxygenation
      level-dependent fMRI signal in the human visual cortex.
AB  - Characteristics of the blood-oxygenation-level-dependent (BOLD) functional
      magnetic resonance imaging (fMRI) signal poststimulus undershoot in the visual
      cortex were studied at varying levels of arterial blood oxygen saturation (Ysat).
      Undershoot with an amplitude of -0.6+/-0.2% appeared after positive BOLD response
      (+1.7+/-0.5%) under control conditions. Cerebral blood volume (CBV), as
      determined with vascular-space-occupancy-dependent fMRI, increased by 26-43%
      during the positive BOLD peak, but the CBV proceeded at baseline level during the
      BOLD poststimulus undershoot. Mild hypoxic hypoxia (Ysat ranging from 0.82 to
      0.89) had no effect on the amplitude or duration of poststimulus undershoot in
      activated BOLD pixels. Hypoxia did not influence CBV during the BOLD poststimulus
      undershoot. In contrast, the positive BOLD signal at the level of all activated
      pixels was smaller in hypoxia than in normoxia. The present results show that the
      BOLD poststimulus undershoot is not influenced by curtailed oxygen availability
      and that, during the undershoot, CBV is not different from resting state.

PMID- 16997069
TI  - A feasibility study of in vivo T1rho imaging of the intervertebral disc.
AB  - PURPOSE: Recent studies have proposed that magnetic resonance (MR) T1rho
      relaxation time is associated with loss of macromolecules. The depletion of
      macromolecules in the matrix of the intervertebral disc may be an initiating
      factor in degenerative disc disease. The purpose of this study was to test the
      feasibility of quantifying T1rho relaxation time in phantoms and intervertebral
      discs of healthy volunteers using in vivo MR imaging at 3 T. MATERIALS AND
      METHODS: A multislice T1rho spiral sequence was used to quantify T1rho relaxation
      time in phantoms with different agarose concentrations and in the intervertebral
      discs of 11 healthy volunteers (mean age=31.3 years; age range=23-60 years;
      gender: 5 females, 6 males). RESULTS: The phantom studies demonstrated the
      feasibility of using spiral imaging at 3 T. The in vivo results indicate that the
      median T1rho value of the nucleus (116.6+/-21.4 ms) is significantly greater
      (P<0.05) than that of the annulus (84.1+/-11.7 ms). The correlations between the
      age of the volunteers and T1rho relaxation time in the nucleus (r2=-0.82;
      P=0.0001) and the annulus (r2=-0.37; P=0.04) were significant. A trend of
      decreasing T1rho values from L3-4 to L4-5 to L5-S1 was evident. CONCLUSION: The
      results of this study suggest that in vivo T1rho quantification is feasible and
      may potentially be a clinical tool in identifying early degenerative changes in
      the intervertebral disc.

PMID- 16997070
TI  - Effects of 3D sampling in (k, t)-space on temporal qualities of dynamic MRI.
AB  - 3D (kx, ky, t)-space analysis is invoked to provide insights into dynamic
      magnetic resonance imaging (DMRI) with arbitrary k-space sampling trajectories.
      The effects of 3D sampling in (kx, ky, t) are analyzed theoretically and verified
      with computer simulation. The analyses show that a 3D sampling pattern that is
      more isotropic in (kx, ky, t)-space and denser around the (kx=0, ky=0, t)-line
      likely results in improved temporal qualities of DMRI. The isotropy of 3D
      sampling is quantified using Voronoi 3D cells and the isoperimetric theorem. This
      3D sampling perspective provides a theoretical framework for understanding the
      temporal qualities of various DMRI methods.

PMID- 16997071
TI  - Quantitative morphologic evaluation of white matter in survivors of childhood
      medulloblastoma.
AB  - In survivors of pediatric brain tumors, cranial radiation therapy can cause a
      debilitating cognitive decline associated with decreased volume in normal
      appearing white matter (NAWM). We applied fractal geometry to quantify white
      matter (WM) integrity in the brain of medulloblastoma survivors. Fractal features
      of WM were evaluated by indices of fractal dimensions (FDs) of WM intensity and
      boundary on T1-weighted magnetic resonance images. The FD index of WM intensity
      was calculated by using a fractional Brownian motion model, and the FD index of
      WM boundary was calculated by using a box-counting method. Fractal features of WM
      on 116 magnetic resonance images of 58 patients with medulloblastoma were
      investigated at the start of therapy (Start TX) and approximately 2 years later
      (After TX). Patients were assigned to one of two groups based on change in NAWM
      volumes. Fractal features in patients with decreased NAWM volume were
      significantly greater After TX, whereas those in patients with increased NAWM
      volumes were not. Multiple linear regression analysis showed that fractal
      features were strongly correlated with NAWM volumes After TX in patients with
      decreased NAWM volume. These results demonstrated significant deficit in NAWM
      integrity and WM density changes in children treated for medulloblastoma.
      Multiple regression analysis illustrated that deficits in NAWM integrity in these
      children may partly explain the decrease in NAWM volume. We conclude that fractal
      geometry can be used to monitor the morphologic effects of neurotoxicity in brain
      tumor survivors.

PMID- 16997072
TI  - Characterization of trabecular bone structure from high-resolution magnetic
      resonance images using fuzzy logic.
AB  - The purpose of this work was to apply fuzzy logic image processing techniques to
      characterize the trabecular bone structure with high-resolution magnetic
      resonance images. Fifteen ex vivo high-resolution magnetic resonance images of
      specimens of human radii at 1.5 T and 12 in vivo high-resolution magnetic
      resonance images of the calcanei of peri- and postmenopausal women at 3 T were
      obtained. Soft segmentation using fuzzy clustering was applied to MR data to
      obtain fuzzy bone volume fraction maps, which were then analyzed with three
      dimensional (3D) fuzzy geometrical parameters and measures of fuzziness.
      Geometrical parameters included fuzzy perimeter and fuzzy compactness, while
      measures of fuzziness included linear index of fuzziness, quadratic index of
      fuzziness, logarithmic fuzzy entropy, and exponential fuzzy entropy. Fuzzy
      parameters were validated at 1.5 T with 3D structural parameters computed from
      microcomputed tomography images, which allow the observation of true trabecular
      bone structure and with apparent MR structural indexes at 1.5 T and 3 T. The
      validation was statistically performed with the Pearson correlation coefficient
      as well as with the Bland-Altman method. Bone volume fraction correlation values
      (r) were up to .99 (P<.001) with good agreements based on Bland-Altman analysis
      showing that fuzzy clustering is a valid technique to quantify this parameter.
      Measures of fuzziness also showed consistent correlations to trabecular number
      parameters (r>.85; P<.001) and good agreements based on Bland-Altman analysis,
      suggesting that the level of fuzziness in high-resolution magnetic resonance
      images could be related to the trabecular bone structure.

PMID- 16997073
TI  - Mapping the parameter space of a T2-dependent model of water diffusion MR in
      brain tissue.
AB  - We present a new model for describing the diffusion-weighted (DW) proton nuclear
      magnetic resonance signal obtained from normal grey matter. Our model is
      analytical and, in some respects, is an extension of earlier model schemes. We
      model tissue as composed of three separate compartments with individual
      properties of diffusion and transverse relaxation. Our study assumes slow
      exchange between compartments. We attempt to take cell morphology into account,
      along with its effect on water diffusion in tissues. Using this model, we
      simulate diffusion-sensitive MR signals and compare model output to experimental
      data from human grey matter. In doing this comparison, we perform a global search
      for good fits in the parameter space of the model. The characteristic
      nonmonoexponential behavior of the signal as a function of experimental b value
      is reproduced quite well, along with established values for tissue-specific
      parameters such as volume fraction, tortuosity and apparent diffusion
      coefficient. We believe that the presented approach to modeling diffusion in grey
      matter adds new aspects to the treatment of a longstanding problem.

PMID- 16997074
TI  - Kalman filtering for reliable estimation of BBB permeability.
AB  - INTRODUCTION: The blood-brain barrier (BBB) plays an important role in the
      pathophysiology of a number of central nervous system disorders. In the past, a
      number of laboratory techniques have been proposed to quantify permeability
      coefficient ki, an important index of barrier function. Recently, magnetic
      resonance imaging (MRI) has been used to estimate ki based on graphical plot
      technique. The MR technique was found to be in good agreement with the gold
      standard, quantitative autoradiography (QAR). However, a reduced image signal-to
      noise ratio, among other factors such as partial volume effects, did not allow
      reliable estimation of permeability coefficients. This proof-of-principle study
      proposes the use of Kalman filter as a filtering technique for a reliable
      estimation of permeability coefficients. The results are compared to those
      obtained using the Wiener filter technique. MATERIALS AND METHODS: MRI
      experiments were performed in Wistar rats (N=2) using a 4.7-T Bruker Biospec MR
      system (Bruker Biospin, Billerica, MA). After acquiring localizer images, T2
      weighted diffusion-weighted imaging images were acquired. Finally, a rapid T1
      mapping protocol was implemented to acquire one pre-gadolinium diethylenetriamine
      pentaacetic acid baseline data set followed by postinjection data sets at 3-min
      intervals for 45 min. Data were postprocessed with and without the application of
      Kalman and Wiener filters to obtain an estimate of ki. RESULTS AND DISCUSSION:
      Comparing T1 maps, Patlak plots and permeability maps with and without the Kalman
      filtering presented several interesting observations. Kalman-filtered Patlak
      plots, compared to nonfiltered plots, showed that discrete data points on the
      plot were closer to the line fit. The number of time points used for the
      construction of the graphical plot had no effect on permeability coefficient
      estimates when the Kalman filter was used. A box-and-whiskers plot showed longer
      Y-error bars for nonfiltered and Wiener data compared to Kalman-filtered data.
      These observations suggest that it may be possible to obtain reliable
      permeability coefficient estimates in a short study time by applying the Kalman
      filter to the data. Future work involves investigating the application of this
      filter on a large-sample-size animal study and evaluating the role of partial
      volume effects on BBB permeability estimation.

PMID- 16997076
TI  - Evaluation of antiangiogenic treatment effects on tumors' microcirculation by
      Bayesian physiological pharmacokinetic modeling and magnetic resonance imaging.
AB  - A physiological pharmacokinetic (PBPK) model was used to estimate tumor
      microcirculation in nude mice with a grafted tumor. The kinetics of a rapid
      clearance blood pool agent, Vistarem, were investigated by dynamic MRI after
      bolus administration. Signal enhancements were recorded in arterial blood and in
      tumor tissue. To analyze these data, we developed a whole-body mathematical model
      of the agent's biodistribution using physiological parameters. The model included
      six compartments: arterial and venous plasma, tumor (split into capillaries and
      interstitium), and the rest of the body (also split into capillaries and
      interstitium). As an application, changes in tumor microcirculation parameters
      were evaluated in mice receiving either an antiangiogenic treatment (ZD4190) or a
      placebo. The analysis was performed in a Bayesian framework, and the model was
      fitted to experimental data using Markov Chain Monte Carlo techniques. Results
      showed a significant difference in tumor microcirculation between the two groups
      of mice when the microcirculation parameters are considered together. This whole
      body physiological model enables to analyze jointly data in tumor tissue and in
      arterial blood. This leads to accurate estimates of microcirculation parameters
      and the evaluation of their uncertainty.

PMID- 16997075
TI  - Dyskinesis in Chagasic myocardium: centerline analysis of wall motion using
      cardiac-gated magnetic resonance images of mice.
AB  - We report on the use of centerline analysis of cardiac-gated magnetic resonance
      images to measure wall motion abnormalities in mice infected with Trypanosoma
      cruzi. To our knowledge, this is the first report of segmental wall motion
      abnormalities in an animal model of Chagas' disease. Chagas' disease patients
      with severe cardiac involvement exhibit mild hypokinesis in an extensive region
      of the left ventricle and dyskinesis in the apical region. We observed dyskinetic
      segments in a similar region of the hearts of infected wild-type mice. Dyskinesis
      was not observed in infected mice lacking macrophage inflammatory protein-1alpha,
      a chemokine that may play an important role in the cardiac remodeling that is
      normally observed in mouse models of Chagas' disease and in human patients. This
      study aimed to demonstrate the utility of cardiac-gated magnetic resonance
      imaging and centerline analysis as a straightforward method for monitoring
      regional left ventricular wall motion in transgenic and/or diseased mice.

PMID- 16997077
TI  - A nonlinear mesh-warping technique for correcting brain deformation after stroke.
AB  - This article presents a warping technique for correcting brain tissue distortion
      on magnetic resonance imaging (MRI) scans due to stroke lesion growth and for
      mapping MRI scans to histological sections. Meshes are imposed upon the images
      for feature specification, and these features are exactly matched in the
      different images to be mapped, while the other voxels are matched by
      interpolation. This technique was tested on serial MR images and histological
      sections that were acquired in a nonhuman primate model of stroke. This technique
      was able to deliver satisfactory warping results. It is simple and robust and can
      be utilized in many applications for comparison of multimodality medical images
      and histological sections.

PMID- 16997078
TI  - Experimental and computational analyses of the effects of slice distortion from a
      metallic sphere in an MRI phantom.
AB  - Susceptibility artifacts due to metallic prostheses are a major problem in
      clinical magnetic resonance imaging. We theoretically and experimentally analyze
      slice distortion arising from susceptibility differences in a phantom consisting
      of a stainless steel ball bearing embedded in agarose gel. To relate the observed
      image artifacts to slice distortion, we simulate images produced by 2D and 3D
      spin-echo (SE) and a view angle tilting (VAT) sequence. Two-dimensional SE
      sequences suffer from extreme slice distortion when a metal prosthesis is
      present, unlike 3D SE sequences for which--since slices are phase-encoded-
      distortion of the slice profile is minimized, provided the selected slab is
      larger than the region of interest. In a VAT sequence, artifacts are reduced by
      the application of a gradient along the slice direction during readout. However,
      VAT does not correct for the excitation slice profile, which results in the
      excitation of spins outside the desired slice location and can lead to incorrect
      anatomical information in MR images. We propose that the best sequences for
      imaging in the presence of a metal prosthesis utilize 3D acquisition, with phase
      encoding replacing slice selection to minimize slice distortion, combined with
      excitation and readout gradient strengths at their maximum values.

PMID- 16997079
TI  - Differences between arterial occlusive and cortical photothrombosis stroke models
      with magnetic resonance imaging and microtubule-associated protein-2
      immunoreactivity.
AB  - The differences between two models of cerebral ischemia [middle cerebral arterial
      transection (MCAT) and cortical photothrombosis (PT)] were explored with
      multiparametric MRI of apparent diffusion coefficient trace (ADCtr), cerebral
      blood flow (CBF) and T1. Microtubule-associated protein-2 (MAP2) immunoreactivity
      sections aligned with the MR images in the same coronal plane were used to map
      the infarct and to guide region-of-interest selection. In ischemic cortex, the
      larger T1 increase in PT versus MCAT (42+/-7% vs. 16+/-5%) is related to the
      different character of edema between these models; yet, neither CBF nor ADCtr
      discriminated between them at 3.5 h, suggesting that different mechanisms of
      ischemic damage to the brain cells resulted in the same ADCtr value. CBF and
      ADCtr were depressed in immediately adjacent ischemic border by 27+/-7% and 47+/
      10%, respectively, in MCAT but not in PT, suggesting marginal perfusion in MCAT.
      CBF in homotopic normal cortex in the opposite hemisphere was higher for PT
      compared with MCAT (199+/-20 and 134+/-10 ml/100 g/min, respectively). Different
      pathological processes in the two models affect CBF, ADCtr and T1 in a unique,
      regionally specific manner. The PT model differs substantially from the MCAT and
      is not a model of cortical ischemia with an appreciable border zone.

PMID- 16997080
TI  - Single-sided mobile NMR with a Halbach magnet.
AB  - A single-sided mobile NMR apparatus with a small Halbach magnet was constructed
      for the first time. It is lightweight, compact and exhibits good sensitivity. The
      weight of the device is only 2 kg, and the NMR signal of the pencil eraser block
      can be detected in one shot using the device. This study describes the
      characteristics of this instrument, including the profile of static magnetic flux
      density, B0, the sensitivity in the depth direction and its effectiveness in one
      dimensional profiling. Its usefulness in differentiating soft materials and
      evaluating the extent of damage of a material is demonstrated based on T2
      relaxation data. The moisture absorbance also can be observed from the increase
      of the echo amplitude of the NMR spin echo signal.

PMID- 16997081
TI  - Noninvasive characterization of gonad maturation and determination of the sex of
      Pacific oysters by MRI.
AB  - The aim of this study was to test the ability of magnetic resonance imaging (MRI)
      technique to characterize gonad development and to determine the sex of live
      Pacific oysters through their shells. A preliminary nuclear magnetic resonance
      (NMR) relaxometry study was conducted to characterize T1 and T2 NMR relaxation
      parameters for the main oyster organs. This showed that T1-weighted MRI sequences
      were most appropriate to optimize contrasts between tissues in images. The
      results showed that gray levels of gonads in images acquired with gradient-echo
      sequence were variably affected by T2* weighting effect. However, the ovaries
      systematically gave a hypersignal in spin-echo T1-weighted images, and stack
      histograms of female oysters showed a peak well separated from that of male
      oysters. An automated method is proposed to quantify the development of oysters
      and their gonad maturation and to identify their sex.

PMID- 16997082
TI  - Thawing of frozen vegetables observed by a small dedicated MRI for food research.
AB  - The thawing process for boiled and frozen edible vegetables was traced by a
      dedicated MRI for food research. The MRI system is small, with a 1.0-T static
      magnetic field, and can be placed in an ordinary research room with a light air
      conditioner. Images of green soybeans, broad beans, okra, asparagus and taro were
      measured by the spin-echo method (echo time=7 ms) with 0.1 or 0.2 s and 1 s
      repetition times. The images appeared along with the thawing time, and signals
      uniformly covered the sliced plane of the samples in the thawed condition.
      Information about the thawing process and tissue structures of the materials was
      obtained during transit thawing conditions. The thawing kinetics were examined
      with increased signal intensity, which were divided into two types. The signal
      increased linearly and saturated for okra and asparagus but exhibited convex
      curves for soybeans, broad beans and taro. The small MRI was stable, its handling
      was simple, and the internal structures of food materials could be accurately
      identified, although the grey-scale of the images was insufficient for
      determining precise textural fluctuations of tissue organization. We conclude
      that the devised MRI is useful for examining the quality of frozen foods and for
      developmental research into frozen foods.

PMID- 16997083
TI  - Permanent sensory nerve impairment following third molar surgery: a prospective
      study.
AB  - OBJECTIVE: This prospective study reports the proportion of permanent sensory
      impairment of the inferior alveolar and lingual nerves and the factors
      influencing such prevalence after the removal of mandibular third molars under
      local anesthesia. STUDY DESIGN: There were 1,087 patients with 1,087 mandibular
      third molars removed under local anesthesia from 1998 to 2003. Standardized data
      collection included the patient's name, age, gender, radiographic position of
      extracted tooth, grade of surgeon, proximity of the inferior alveolar nerve, and
      the prevalence of lingual and/or inferior alveolar nerve paresthesia. RESULTS:
      Inferior alveolar nerve injury was 4.1% 1 week after surgery and decreased to
      0.7% after 2 years of follow-up, and alteration in tongue sensation occurred in
      6.5% of patients 1 week after surgery and decreased to 1.0% after 2 years of
      follow-up. CONCLUSION: The experience of the operator was found to be a
      significant factor in determining both permanent lingual nerve (P=.022) and
      permanent inferior alveolar nerve paresthesia (P=.026).

PMID- 16997084
TI  - Cyclic fatigue of different nickel-titanium endodontic rotary instruments.
AB  - OBJECTIVE: A comparative study of the fatigue resistance of rotary nickel
      titanium endodontic instruments was performed with the aim of assessing the
      influence of both instrument design and surface treatment on flexural fracture.
      STUDY DESIGN: To evaluate fatigue resistance of different rotary instruments, a
      total of 120 instruments were tested; these came from different sources: ProFile,
      RaCe, K3, Hero, and Mtwo. To compare the effect of electro-polishing procedures
      on fatigue resistance, a group of RaCe instruments (which are normally electro
      polished) without surface treatment was used. A scanning electron microscope
      (SEM) study for each instrument was performed before and after fatigue study to
      determine the mode of fracture and the aspect of tips and cross-sectional surface
      areas. RESULTS: ProFile instruments gave the best values for fatigue resistance.
      It was seen that for RaCe instruments the surface treatment reduces the presence
      of micro-cracks, surface debris, and machining damage. CONCLUSIONS: This study
      shows that the instrument design often proves to be an important factor in the
      fatigue resistance of NiTi rotary instruments. In RaCe instruments the electro
      polishing surface treatment increases the fracture-related fatigue resistance.

PMID- 16997085
TI  - Cellular toxicity of mineral trioxide aggregate mixed with an alternative
      delivery vehicle.
AB  - OBJECTIVE: Mineral trioxide aggregate (MTA) mixed with water has a short working
      time, delayed setting, and poor consistency. A preliminary study suggested that
      substituting KY Jelly as a mixing vehicle improves the working properties of MTA.
      The present study compared the biocompatibility of white MTA mixed with water or
      with KY Jelly to that of Fuji II cement and of silver amalgam. STUDY DESIGN:
      Periodontal ligament (PDL) cells were cultured using standard laboratory
      procedures. Cells were plated in wells at a density of 10,000 cells/well. The
      test materials were mixed and eluate placed in contact with the PDL cells. Cell
      viability was determined by measuring mitochondrial enzyme activity using the 3
      (4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenytl)-2H
      tetrazolium inner salt assay. Cytotoxicity was also measured in terms of cell
      lysis using the lactate dehydrogenase assay. The assays were completed in
      triplicate after time intervals of 24, 48, and 72 h. Mean cell counts were
      calculated and converted to a percentage of control results. A 2-way analysis of
      variance and Tukey honestly significant difference post-hoc test were performed
      to determine statistical significance. RESULTS: Eluate extractions from all
      materials caused significantly less cell viability and more cell death than
      control eluate (medium only) at all eluate time points tested. However, at 72 h
      the MTA/water, MTA/KY, and amalgam eluate extractions led to significantly better
      cell viability than the Fuji II eluates. However, there was significantly greater
      cell lysis for all eluates from the tested materials at 72 h than at 24 h.
      CONCLUSIONS: Within the limitations of this in vitro study, we conclude that
      MTA/KY, MTA/water, and amalgam have similar biocompatibility regarding effects of
      their eluates on human PDL cells, and eluates from all 3 materials demonstrate
      better biocompatibility than eluates derived from a resin-modified glass ionomer
      cement.

PMID- 16997086
TI  - Maxillary calcifying epithelial odontogenic (Pindborg) tumor presenting with
      abnormal eye signs: case report and literature review.
AB  - Calcifying epithelial odontogenic tumors (CEOT) are uncommon, accounting for less
      than 1% of all odontogenic tumors. The CEOT, since its description by Pindborg in
      1958 as a separate pathologic entity, is commonly known as the Pindborg tumor. We
      present an unusual case of such a tumor in the maxilla presenting with abnormal
      eye signs. The case demonstrates the use of a Le Fort I down-fracture osteotomy
      approach to maxillary tumors.

PMID- 16997087
TI  - Dens invaginatus type II: case report with 2-year radiographic follow-up.
AB  - Dens invaginatus is a malformation of teeth probably resulting from an infolding
      of the dental papilla during tooth development. Clinically, it is frequently
      characterized by unusual crown morphology. It is common to see peg- or barrel
      shaped teeth. The present case describes dens invaginatus in a lateral maxillary
      incisor (Oehler type II) with a barrel-shaped crown of a 12-year-old female
      patient; endodontic treatment and adhesive restoration were performed. After two
      years the tooth showed no signs of pathosis.

PMID- 16997088
TI  - The changing pattern of analgesic and anti-inflammatory drug use in cleft lip and
      palate repair.
AB  - OBJECTIVE: This work aimed at performing a retrospective and comparative
      investigation of pharmacological therapeutic approach for pain and inflammation
      control for cleft lip and/or palate repair. STUDY DESIGN: Medical charts from
      2000 patients who underwent surgical procedures at the Hospital for
      Rehabilitation of Craniofacial Anomalies, University of Sao Paulo (HRAC-USP),
      Brazil, were assessed to obtain information regarding type of cleft, surgical
      procedure, and analgesic and anti-inflammatory drugs prescribed. The first 1000
      consecutive surgeries performed in 1992 and 2002 were assessed. RESULTS:
      Different analgesic and anti-inflammatory agents-nonsteroidal anti-inflammatory
      drugs (NSAIDS), steroids, and opioids-were given to patients perioperatively and
      postoperatively. NSAIDS were given to almost all patients (97.03% in 1992 and
      99.88% in 2002, P > .05). Steroid administration increased in 2002 (8.66% versus
      17.71%, P < .05). Opioids were administered only in 2002 (50.31%, P < .05).
      CONCLUSION: NSAIDS, steroids, and opioids were used for pain and inflammation
      control in cleft lip and palate repair at HRAC-USP. A change in the pattern of
      analgesic and anti-inflammatory drug use was observed when comparing 1992 and
      2002. More potent compounds, such as opioids, were used in 2002 in a significant
      percentage of all the surgical procedures.

PMID- 16997089
TI  - Case report: brain and liver abscesses caused by oral infection with
      Streptococcus intermedius.
AB  - Organ abscesses are a rare and life-threatening complication mostly of
      hematogenously disseminated infections. We report a case of brain and liver
      abscesses. Identification of the lesions was made by contrast-enhanced computed
      tomography (CT) and magnetic resonance imaging (MRI), respectively. An oral
      examination comprised an oral focus of infection. Streptococcus intermedius was
      isolated from oral smear, liver and ventricular drainage, and blood sample. After
      the commencement of antibiotic therapy, drainage of abscesses and oral
      rehabilitation, complete recovery was noted.

PMID- 16997090
TI  - Monomorphic Epstein-Barr virus (EBV)-associated large B-cell posttransplant
      lymphoproliferative disorder presenting as a tongue ulcer in a pancreatic
      transplant patient.
AB  - Posttransplant lymphoproliferative disorders are a group of lymphoid
      proliferations and lymphomas that develop as a consequence of immunosuppression
      in recipients of solid organ or bone marrow allografts. We describe an unusual
      oral presentation of posttransplant Epstein-Barr virus-associated diffuse large B
      cell lymphoma in a 45-year-old woman after pancreatic transplant.

PMID- 16997091
TI  - Darier disease affecting the gingival and oral mucosal surfaces.
AB  - Darier disease is an uncommon genodermatosis reflecting defective desmosomal
      structure and function. The present report details the oral features of a patient
      with well-characterized Darier disease and reviews current knowledge of the
      genetic basis of this genodermatosis that can often affect the craniofacial
      tissues.

PMID- 16997092
TI  - Central neurilemmoma of the jaw in concurrence with radicular cyst: a case
      report.
AB  - We report the features of a central neurilemmoma in the mandible of a patient
      having an inflammatory apical dental (radicular) cyst in the same region. A 29
      year-old woman complained of numbness on the right side of the lower lip of 3
      months duration and noted following endodontic therapy to the right mandibular
      first molar tooth. Panoramic radiography revealed a bilocular radiolucency in the
      right body of the mandible. Excisional biopsy was performed. The histopathology
      revealed neurilemmoma of the mandible in concurrence with inflammatory apical
      dental (radicular) cyst. No recurrence was detected during a 1-year follow-up.

PMID- 16997093
TI  - Sole radiographic expression of rheumatoid arthritis in the temporomandibular
      joints: a case report.
AB  - We present an unusual case of rheumatoid arthritis. The patient had no
      radiographic findings in any joints of the body expected to show symptoms of the
      disease, such as phalangophalangeal joints of the hands and metacarpophalangeal
      joints. Instead, the patient had radiographic findings in the temporomandibular
      joints, which are not commonly involved in the disease and its activity.

PMID- 16997094
TI  - Temporomandibular joint osteochondritis dissecans: case report.
AB  - BACKGROUND: Osteochondritis dissecans is a process in which segment(s) of
      cartilage separate from an articular surface. It is most often reported in the
      larger joints of the body, including the knee, elbow, hip, wrist, and ankle.
      Involvement of the temporomandibular joint (TMJ) is exceedingly rare. OBJECTIVES:
      To describe a probable case of osteochondritis dissecans and discuss the
      differential diagnosis for this condition. STUDY DESIGN: In addition to clinical
      examination the patient was imaged using panoramic radiography, computed
      tomography and magnetic resonance imaging. RESULTS: Panoramic radiography showed
      separation of 2 rounded fragments superior to the right mandibular condyle. These
      were more precisely located using 3-dimensional computerized tomographic
      reconstructions. Magnetic resonance imaging demonstrated the right condyle as
      having low signal intensity area on T1-weighted images and a heterogeneous signal
      on T2-weighted images, with low signal dominance. No abnormality was apparent in
      the left TMJ. CONCLUSIONS: The patient was treated nonsurgically with a splint,
      occlusal adjustment, physiotherapy, and nonsteroidal antiinflammatory
      medications. Maximum mouth opening has increased from 24 mm to 39 mm 6 months
      following initiation of treatment, and pain has subsided.

PMID- 16997096
TI  - Spontaneous re-eruption of intruded permanent incisors: five case reports.
AB  - This report presents 5 cases of intrusive luxation in immature permanent central
      incisors. The intruded incisors, with careful monitoring, were allowed to
      spontaneously re-erupt, which avoided the need to reposition the tooth either
      orthodontically or surgically. All of the teeth re-erupted spontaneously in a few
      months. The root development continued in all of the cases and all pulps remained
      vital. There were no other signs of pulpal and/or periapical pathology. It can be
      concluded that intruded immature permanent teeth can spontaneously re-erupt,
      conserve their vitality, and continue their root development without any surgical
      or orthodontic management.

PMID- 16997095
TI  - Labiomandibular paresthesia caused by endodontic treatment: an anatomic and
      clinical study.
AB  - Labiomandibular paresthesia after root canal treatment is an accident that is
      still too frequent despite the development of new endodontic techniques. The aim
      of this anatomical and clinical study is to advance the understanding of how
      accidents occur so as to avoid them. This anatomical study made it possible to
      determine the variability of proximity of the apex of the tooth root to the
      mandibular bundle, as well as the relationship between the nerve and its
      satellite artery, and to understand how endodontic filling material spreads into
      the cancellous bone. The clinical study, which included examination with
      conventional radiology as well as with imaging techniques, enabled us to identify
      the exact location of the filling material in relation to the mandibular bundle
      and to correlate this to the occurrence of clinical symptoms and their diverse
      manifestations.

PMID- 16997097
TI  - Immunohistochemical expression of fibronectin and tenascin after direct pulp
      capping with calcium hydroxide.
AB  - The aim of this study was to investigate the expression of 2 extracellullar
      matrix glycoproteins, fibronectin (FNC) and tenascin (TNC), following direct pulp
      capping with calcium hydroxide (CH). Third molars scheduled for extraction were
      used. Standardized class I cavities with pulp exposures were prepared. After
      control of bleeding, CH powder was applied in the exposure sites, which were
      covered with CH cement (Dycal; Dentsply) and the cavities were filled with zinc
      oxide-eugenol cement. Three teeth were extracted at each post-treatment period
      (1, 7, 14, and 30 days). Demineralized and paraffin-embedded specimens were
      stained for histologic technique (hematoxylin-eosin) and for immunohistochemical
      analysis. Anti-TNC and anti-FNC monoclonal antibodies were used with the
      streptavidin-biotin complex method. Generally, similar patterns of
      immunohistochemical expression were observed for TNC and FNC in the pulp tissue
      as a whole. In the exposure site, TNC immunostaining increased over time,
      exhibiting a thicker immunostaining pattern within 30 days. The
      imunohistochemical technique showed expression of both glycoproteins during pulp
      healing process.

PMID- 16997098
TI  - Endodontic treatment of an unusual connation of permanent mandibular molars: a
      case report.
AB  - A 27-year-old patient with an anomalous mandibular molar was referred for
      endodontic therapy. Clinical and radiographic examination revealed the connation
      of a second mandibular molar with a third molar. Challenging endodontic therapy
      was performed in the unusual connated molars. A 2-year recall showed good
      treatment result.

PMID- 16997099
TI  - Histologic evaluation of direct pulp capping with a self-etching adhesive and
      calcium hydroxide in beagles.
AB  - OBJECTIVE: To evaluate the pulpal response of beagles following direct pulp
      capping with Clearfil SE Bond (SB), a self-etching adhesive. STUDY DESIGN: One
      hundred thirty sound teeth from 6 male beagles were used. One hundred twenty
      teeth had their pulp mechanically exposed at the bottom of the class V cavities
      and were divided into 2 groups. In group 1, teeth were capped with SB; group 2
      teeth were capped with calcium hydroxide cement (CH). Ten teeth were kept intact
      as an untreated control group. After 7, 30, and 90 days, 40 teeth from 2 beagles
      were extracted and processed for light microscopic examination. RESULTS: After
      the 7-day observation period, inflammatory reaction in the SB group was similar
      to that of the CH group (P > .05). After the 30-day and 90-day observation
      periods, inflammatory reaction was slight in both groups, but less dentin bridge
      formation was observed in specimens from the SB group than in those from the CH
      group (P < .05). CONCLUSION: SB showed good biocompatibility with pulp, but its
      ability to induce reparative dentin was lower than that of CH.

PMID- 16997100
TI  - Vertical distraction osteogenesis of fibula transplant for mandibular
      reconstruction: a case report.
AB  - Bone continuity defects in the mandible are caused by tumor surgery, trauma,
      infection, or osteoradionecrosis. Today, reconstruction of long-span mandibular
      defects with a free fibular flap is a routine procedure. However the bone height
      of the mandible after reconstruction is about half that of the dentulous
      mandible. Therefore, the deficiency in bone height makes implant placement
      impractical. In our case, because it was necessary to restore the mandibular
      height, a vertical distraction osteogenesis was performed on the grafted mandible
      of the patient who was referred to our clinic with a reconstructed mandible owing
      to a gunshot injury. As a result, the vertical discrepancy between the fibula and
      the native hemimandible of the patient was corrected. And the placement of dental
      implants was performed without any complications. In conclusion, we believe that
      the vertical distraction osteogenesis of free vascularized fibula flaps is a
      reliable technique that optimizes implant positioning for ideal prosthetic
      rehabilitation.

PMID- 16997101
TI  - Intentional replantation of a mandibular molar: case report and 14-year follow
      up.
AB  - This case report describes the nonsurgical endodontic treatment and intentional
      replantation of a mandibular molar and its nearly 14-year follow-up. A 56-year
      old woman sought treatment with complaint of discomfort and sensitivity in the
      mandibular left area. The radiographic examination showed that the mandibular
      left first molar was endodontically treated, with over-instrumentation of the
      distal root and unsatisfactory obturation on the mesial root. A large periapical
      lesion was observed surrounding the roots. In view of the patient's limited
      interocclusal space and objection to undergo an apical surgery, intentional
      replantation was suggested as an alternative. The patient returned for clinical
      and radiographic follow-up at 15 days, 40 days, 6 months, 12 months, and once
      yearly thereafter. At the last visit, after 14 years, no painful symptomatology
      was reported, probing depth was no greater than 3 mm, the periradicular area had
      normal appearance and no evidence of root resorption or periapical lesion.

PMID- 16997102
TI  - Effects of different root canal obturation techniques on bacterial penetration.
AB  - OBJECTIVES: The aim of this study was to compare bacterial penetration following
      obturation with 5 different techniques. STUDY DESIGN: This study was performed on
      120 teeth including negative control (n = 10), positive control (n = 10), and
      experimental groups (n = 100). One hundred teeth were randomly divided into 5
      groups of 20 teeth each and obturated with System B (Sb), Lateral Compaction
      (Lc), Thermafil (T), Single ProTaper Gutta-percha (P), and laterally compacted
      ProTaper Gutta-percha (PLc). Enterococcus faecalis was used for determination of
      the bacterial penetration. Evaluation was carried out for 60 days. RESULTS: At 30
      days, the chi2 test showed that the slowest penetration was observed in Group Sb
      and Group PLc, which were not significantly different from each other. The
      fastest penetration in the all experimental groups was observed in Group T and
      Group P, which were not significantly different from one another. Also, there was
      no statistically significance difference (P > .05) among all groups at 60 days.
      CONCLUSION: It may be concluded that under the conditions of this study System B
      and laterally compacted ProTaper Gutta-percha prevent bacterial penetration of
      the root canal at 30 days. Furthermore, there was no difference among obturation
      techniques at 60 days.

PMID- 16997103
TI  - Efficiency of NaOCl and laser-assisted photosensitization on the reduction of
      Enterococcus faecalis in vitro.
AB  - OBJECTIVE: To investigate the action of a red laser associated with a
      photosensitizer on the reduction of Enterococcus faecalis in dental root canal in
      vitro. STUDY DESIGN: Thirty prepared teeth with single canals were contaminated.
      The chemical group was irrigated with 0.5% NaOCl and left flooded for 30 minutes.
      In the laser group, a paste-based photosensitizer was maintained in the root
      canals for 5 minutes, and then irradiated with a laser at 685 nm using an optical
      fiber for an E of 1.8 J during 3 minutes. After treatment, the canal content was
      collected, serially diluted, and cultured to determine the number of colony
      forming units. RESULTS: Photosensitizer alone or laser alone did not have any
      bactericidal effect. Chemical solution reduced viable bacteria in 93.25%. Laser
      photosensitization resulted in a reduction of 99.2%, a significantly higher
      bacterial reduction than NaOCl. CONCLUSION: Laser photosensitization was
      effective for reducing E. faecalis in root canals and could be an adjunct to
      endodontic treatment.

PMID- 16997104
TI  - The effect of sodium hypochlorite on the surface characteristics and fatigue
      resistance of ProFile nickel-titanium instruments.
AB  - OBJECTIVE: Evaluate the effect of 5.25% NaOCl on the surface characteristics and
      fatigue resistance of ProFile. STUDY DESIGN: Eighty new ProFile instruments were
      divided into 1 control group (CG) and 3 experimental groups (EG1, EG2, EG3).
      Instruments of EG1 were immersed in 5.25% NaOCl for 24 hours. Instruments of EG2
      and EG3 shaped 10 curved root canals, using, respectively, deionized water and
      5.25% NaOCl as irrigants. Surface characteristics were observed by scanning
      electron microscopy. All instruments were then submitted to fatigue tests. Two
      way ANOVA tests were employed to compare the results. RESULTS: Surface
      characteristics showed no alteration after the immersion tests. The fatigue
      resistance of instruments in EG2 and EG3 was significantly lower than in CG and
      EG1. CONCLUSIONS: Immersion of ProFile in 5.25% NaOCl for 24 hours had no
      influence on surface characteristics and fatigue resistance. Simulated clinical
      use was a decisive factor in the decrease of fatigue life.

PMID- 16997105
TI  - Tales of academic dishonesty and what do we do about it?

PMID- 16997106
TI  - Oral bowenoid papulosis in an HIV-positive male.

PMID- 16997108
TI  - Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for
      diagnosis, staging and management.

PMID- 16997109
TI  - Individual preformed titanium meshes for orbital fractures.
AB  - OBJECTIVES: The aim of this investigation was to develop and test the accuracy of
      a procedure for fabricating individual preformed titanium meshes for orbital
      fractures. STUDY DESIGN: Preoperative CT datasets from five patients with orbital
      fractures were used for 3D reconstruction by mirroring the unaffected side onto
      the defective one, resulting in a new sub-volume. A template for adaptation of
      the titanium mesh was produced by applying these sub-volumes. Navigation-aided
      procedures guaranteed the exact placement of the preformed mesh during the
      operation. RESULTS: The accuracy of the reconstructed orbital floor was
      determined to be approximately 1 mm, which lies within the technical limit of
      detection. CONCLUSION: These results indicate a further application or navigation
      aided reconstruction, which will serve as a pilot project for further
      investigations. Clustered databases of patients will be used to produce various
      template sets, reflecting ideal skeletons, according to age, sex, and other
      patient variables. These could be used for manufacturing preformed osteosynthesis
      templates.

PMID- 16997110
TI  - Do pathologies associated with impacted lower third molars justify prophylactic
      removal? A critical review of the literature.
AB  - Surgical removal of impacted lower third molars is widely carried out in general
      dental practice and in many institutional clinics. Despite the fact that there
      are well established indications for the removal of impacted lower third molars,
      prophylactic removal of these teeth is still being universally practiced. Some
      reports have estimated that the proportion of impacted third molars that are
      removed when no clinically sound justification for surgery is present is between
      18% and 50.7%. Justifications for prophylactic surgery include the need to
      minimize the risk of disease (cysts and tumors) development, reduction of the
      risk of mandibular angle fracture, increased difficulty of surgery with age, and
      that third molars have no definite role in the mouth. This article critically
      examines the literature regarding the relationship between impacted lower wisdom
      teeth, cysts and tumor development, and mandibular fractures.

PMID- 16997111
TI  - Short-term therapeutic outcome of intra-articular high molecular weight
      hyaluronic acid injection for nonreducing disc displacement of the
      temporomandibular joint.
AB  - In a patient with temporomandibular disorder who does not respond to conservative
      treatment, treatment with intra-articular injection of high molecular weight
      sodium hyaluronate can be suggested. In our study, 27 patients with nonreduced
      disc displacement were diagnosed clinically and confirmed by magnetic resonance
      imaging. The age range was from 21 to 63 years old, with a mean of 39.3 years.
      Two cycles of injection of high molecular weight sodium hyaluronate was performed
      on alternative weeks. Pain intensity was measured by the visual analog scale.
      Maximal mouth opening, clicking joint noise, and lateral movement were measured
      before and after injection for more than 6 months. Reduction of pain intensity
      and improvement in the maximum mouth opening parameter was statistically
      significant. In conclusion, this intra-articular injection using high molecular
      weight sodium hyaluronate looks very positive for patients affected by nonreduced
      disc displacement and is encouraged to be used as a primary treatment of
      temporomandibular joint dysfunction.

PMID- 16997112
TI  - Evaluation of mandibular block using a standardized method.
AB  - The purpose of this prospective randomized study was to investigate the
      manifestations and efficiency of mandibular block (MB) using a standardized
      method. In this study, 123 patients requiring MB were randomly assigned to
      receive MB using a repeated measures design. Mandibular block was administered in
      each patient by using 2.1 mL of 2% lidocaine with 1:100 000 epinephrine for the
      inferior alveolar nerve, lingual nerve, and/or buccal nerve. Clinical parameters
      including the electric pulp test and test for soft tissue sensation using a sharp
      dental explorer were assessed on both the operated side and contralateral side
      before and 5, 10, and 15 minutes after injection, and at the end of surgical
      procedure. Results of the test of the contralateral tooth served as the control
      group. No response to the electric pulp test at a maximum output (80 readings)
      was used as the criterion for pulpal anesthesia. Results obtained with electric
      pulp test and sharp explorer test were not significantly different during various
      intervals on the contralateral side, indicating the reliability of this
      standardized method for assessing MB. The MB technique achieved a high rate of
      subjective numbness (100%) according to the perception of the patients of overall
      numbness and lip numbness. Overall anesthetic success rates of pulpal anesthesia
      were 5.7% for the central incisor, 38.2% for the canine, 55.3% for the first
      premolar, and 90.2% for the first molar. No significant difference was found in
      the efficiency of anesthesia related to sex or age of the patients. A slower
      onset of pulpal anesthesia after MB was found for the anterior teeth than for the
      posterior teeth. This study suggests that the use of a standardized method might
      produce a clearer and more comprehensive evaluation of the efficiency and
      manifestations of MB.

PMID- 16997113
TI  - Lip hypertrophy secondary to cyclosporine treatment: a rare adverse effect and
      treatment considerations.
AB  - Gingival hypertrophy is a well-known and extensively documented undesirable side
      effect of cyclosporine in posttransplant patients. However, severe lip
      enlargement associated with cyclosporine is less recognized and has seldom been
      reported in the literature. Lip enlargement may lead to social, physical, and
      psychological stress, especially in the older childhood and adolescent age
      groups. We present a case of marked lip hypertrophy and concomitant gingival
      hypertrophy secondary to cyclosporine (Neoral) treatment in a pediatric bilateral
      lung transplant recipient. We also discuss the various side effects and treatment
      considerations available including more recent substitution therapy. Cyclosporine
      has most effectively and conclusively enabled transplantation of solid organs by
      reducing transplant-associated morbidity. We believe clinicians should be
      knowledgeable and aware of lip hypertrophy associated with cyclosporine use. This
      rare and less understood adverse effect should be recognized during the clinical
      evaluation of the posttransplant patient.

PMID- 16997115
TI  - Oral habits and their association with signs and symptoms of temporomandibular
      disorders in adolescents: a gender comparison.
AB  - OBJECTIVES: The prevalence of oral parafunctions and signs and symptoms of
      temporomandibular disorders (TMD) in female and male adolescents were compared
      and their relationship to one another evaluated. STUDY DESIGN: The study
      consisted of 314 adolescents (136 males and 178 females). Each participant filled
      out a questionnaire regarding their oral habits and symptoms of TMD. A clinical
      examination was carried out regarding signs of TMD. RESULTS: Generally, the
      prevalence of most oral habits was higher among adolescent females than males.
      Most examined signs and symptoms of TMD showed a statistically significant higher
      prevalence among females. Gender and nearly all oral habits were a risk factor
      for TMD. CONCLUSIONS: Adolescent females had a higher prevalence of TMD signs and
      symptoms and carried out oral habits more intensively. Parafunctional activity
      may be another contributing factor in the discrepancies found in the prevalence
      of signs and symptoms between the sexes. Parafunctional habits and gender may be
      risk factors of TMD.

PMID- 16997114
TI  - An evaluation on the efficacy and safety of amlexanox oral adhesive tablets in
      the treatment of recurrent minor aphthous ulceration in a Chinese cohort: a
      randomized, double-blind, vehicle-controlled, unparallel multicenter clinical
      trial.
AB  - OBJECTIVE: The objectives of this study were to clinically determine the topical
      efficacy and safety of amlexanox oral adhesive tablets in the treatment of
      recurrent minor aphthous ulcerations (MiRAU) in a Chinese cohort. STUDY DESIGN: A
      randomized, double-blind, vehicle-controlled, unparallel multicenter clinical
      trial was carried out. The tablets were applied by subjects themselves 4 times a
      day for 5 days. Four parameters (pain scale, size change, degree of erythema and
      exudation, and efficacy index) were recorded both before (baseline) and during
      the trial (on the morning of days 4 and 6). RESULTS: There were 104 and 108
      subjects who fulfilled the trial in the amlexanox group and the vehicle-control
      group, respectively. Group differences for all parameters but degree of erythema
      and exudation of day 4 were statistically significant both for the day 4 visit
      and the day 6 visit (P < .05). No systemic side effects were reported.
      CONCLUSIONS: Amlexanox oral adhesive tablets are effective and safe in reducing
      aphthous ulcer pain and lesion size, as well as erythema and exudation in this
      Chinese cohort.

PMID- 16997116
TI  - Candida albicans binds to saliva proteins selectively adsorbed to silicone.
AB  - Explanted voice prostheses obtained from 5 patients at the time of prosthesis
      replacement were consistently colonized by yeast, in particular Candida albicans.
      A simple, reproducible, in vitro model of C. albicans adherence to saliva-coated
      voice prosthesis silicone was developed. Whole saliva promoted adherence of C.
      albicans to silicone in a dose-dependent manner. Saliva rinses from voice
      prosthesis patients also promoted binding of C. albicans to silicone in vitro
      (mean adherence 14.9% +/- 2.8% of input C. albicans cells). This was
      significantly higher than C. albicans adherence to silicone in the absence of
      saliva (P < .001) or adherence promoted by saliva rinses from healthy volunteers
      (P < .005). Polyacrylamide gel electrophoresis analysis and a blot overlay
      adherence assay revealed that certain salivary proteins were selectively adsorbed
      to silicone and that C. albicans yeast cells adhered specifically to the adsorbed
      salivary proteins.

PMID- 16997117
TI  - Assessment of CD43 expression in adenoid cystic carcinomas, polymorphous low
      grade adenocarcinomas, and monomorphic adenomas.
AB  - OBJECTIVE: Distinguishing between adenoid cystic carcinoma (ACC), polymorphous
      low-grade adenocarcinoma (PLGA), and monomorphic adenoma (MA) can occasionally
      pose a diagnostic challenge. It is of interest to identify a marker that can
      differentiate between these tumors. CD43 is a sialoglycoprotein that is typically
      expressed by hematopoietic cells and their derivative neoplasms, although
      positivity in epithelial tumors has been recently recognized. Our aim was to
      investigate CD43 immunoreactivity in ACCs, PLGAs, and MAs. STUDY DESIGN: Formalin
      fixed paraffin-embedded sections from 40 salivary gland tumors (12 ACCs, 14
      PLGAs, and 14 MAs) accessioned from 1989 to 2002 were retrieved from the files at
      the Department of Pathology, Long Island Jewish Medical Center.
      Immunohistochemical staining with anti-CD43 monoclonal antibody was performed.
      RESULTS: Cytoplasmic and membranous immunoreactivity was detected in 12/12 ACCs
      (100%), 1/14 PLGAs (7.1%), and 3/14 MAs (21.4%). CONCLUSIONS: CD43 appears to be
      preferentially expressed in salivary gland ACCs compared to PLGAs and MAs.
      Although the mechanism of this overexpression remains obscure at this time, our
      results suggest that the use of CD43 immunostaining as an adjunct to histological
      examination may be helpful in differentiating ACC from its mimics.

PMID- 16997118
TI  - Partial facial hemihyperplasia with 9 years of evolution: case report and review
      of the literature.
AB  - Partial facial hemihyperplasia is a rare maxillofacial dysmorphosis of debatable
      etiology, and is frequently associated with relatively serious appearance and
      functional disorders depending on the degree of hyperplasia. We report here a
      case of partial facial hemihyperplasia with 9 years of evolution, describing the
      alterations observed during the follow-up period and discussing the main aspects
      of this poorly known entity.

PMID- 16997119
TI  - Rosai-Dorfman disease of the mandible.
AB  - Rosai-Dorfman disease (RDD) is a rare, non-neoplastic histiocytosis most commonly
      characterized by painless, massive cervical lymphadenopathy. Over half of all
      patients with lymph node involvement also demonstrate extranodal disease, with
      most affected individuals exhibiting lesions within the region of the head and
      neck. Oral manifestations of RDD are extremely rare, and almost always identified
      in association with nodal or other extranodal disease. However, rare examples of
      extranodal RDD, including oral RDD, without clinical or radiographic evidence of
      concomitant lymph node involvement, have also been described. We report a rare
      case of solitary, extranodal RDD arising within the mandible in a pregnant woman.
      To our knowledge, this case represents only the fourth documented example of
      solitary oral RDD. A review of the clinical and histopathologic features
      associated with RDD is also presented.

PMID- 16997120
TI  - A study of the utility of silver nucleolar organizer regions in categorization
      and prognosis of salivary gland tumors.
AB  - BACKGROUND: this study aimed at assessing the utility of silver nucleolar
      organizer region (AgNOR) staining in categorization and prognostication of
      salivary gland tumors. METHODS: Twenty-seven malignant salivary gland tumors, 16
      benign neoplasms, and 6 chronic sialadenitis lesions were stained using the
      technique described by Ploton et al. (1986). RESULTS: The mean AgNOR counts for
      inflammatory lesions (1.67 +/- 0.19) and benign neoplasms (1.67 +/- 0.11), were
      less than for malignant neoplasms (3.59 +/- 0.55), P < .05. There was no
      significant difference between the mean AgNOR counts of different specific
      histological types and grades of malignant neoplasms. In addition, no correlation
      was found between mean AgNOR counts and the clinical course of malignant or
      benign salivary gland neoplasms. CONCLUSION: Our results suggest that AgNOR
      staining is useful for distinguishing benign from malignant lesions, but is
      neither helpful for discriminating between histological types and grades of
      malignant neoplasms, nor prognostication of malignant salivary gland neoplasms.

PMID- 16997121
TI  - The efficacy of magnetic resonance imaging in the diagnosis of degenerative and
      inflammatory temporomandibular joint disorders: a systematic literature review.
AB  - OBJECTIVE: To evaluate the evidence for the efficacy of magnetic resonance
      imaging (MRI) in the diagnosis of disk position and configuration, disk
      perforation, joint effusion, and osseous and bone marrow changes in the
      temporomandibular joint. STUDY DESIGN: A PubMed literature search with specific
      indexing terms and a hand search were made. Two reviewers assessed the level of
      evidence of relevant publications as high, moderate, or low. Based on this, the
      evidence grade for diagnostic efficacy was rated as strong, moderately strong,
      limited, or insufficient. RESULTS: The literature search yielded 494 titles, of
      which 22 were relevant. No publication had a high level of evidence, and 12 had
      moderate and 10 low levels of evidence. The evidence grade for diagnostic
      efficacy expressed as sensitivity, specificity, and predictive values was
      insufficient. CONCLUSION: That evidence is insufficient emphasizes the need for
      high-quality studies on the diagnostic efficacy of MRI, incorporating accepted
      methodologic criteria.

PMID- 16997122
TI  - The effect of lighting conditions on caries interpretation with a laptop computer
      in a clinical setting.
AB  - OBJECTIVE: To test the null hypothesis of no difference in caries detection in
      dim, bright, and hooded environments for laptop viewing of intraoral radiographs.
      STUDY DESIGN: Extracted posterior teeth were imaged with posterior bite wing
      geometry by using storage phosphor plates. Images were displayed on a laptop
      computer placed in 3 lighting environments. Six dental students and 6 faculty
      observers scored the caries status of proximal surfaces. Responses were compared
      to histologic ground truth by using receiver operating characteristic (ROC)
      analysis and other measures of accuracy. Performance was also compared to
      photometer-measured light levels and time spent in observation. RESULTS: ROC A(Z)
      was significantly higher for faculty using hooded displays (0.87) than in a
      bright clinical environment (0.79; P = .04). Student performance was highly
      variable and not significantly different in any of the lighting environments.
      CONCLUSION: The ability to detect caries by experienced clinicians may be
      improved by hooding laptop displays in bright clinical environments.

PMID- 16997123
TI  - In vitro evaluation of the antimicrobial activity of calcium hydroxide combined
      with chlorhexidine gel used as intracanal medicament.
AB  - The aim of this study was to investigate the antimicrobial activity of calcium
      hydroxide (Ca(OH)2) combined with 2% chlorhexidine gluconate (CHX) gel against
      endodontic pathogens and to compare the results with the ones achieved by Ca(OH)2
      mixed with sterile water and by CHX gel alone. Two methods were used: the agar
      diffusion test and the direct contact test. Ca(OH)2 + 2% CHX gel produced
      inhibitory zones ranging from 2.84 to 6.5 mm, and required from 30 seconds to 6
      hours to eliminate all tested microorganisms. However, 2% CHX gel showed the
      largest microbial growth zones from 4.33 to 21.67 mm, and required 1 minute or
      less to inhibit all tested microorganisms. A paste of Ca(OH)2 plus sterile water
      inhibited only the microorganisms with which it was in direct contact and
      required from 30 seconds to 24 hours to kill all tested microorganisms. In
      conclusion, 2% CHX gel + Ca(OH)2 showed better antimicrobial activity than
      Ca(OH)2 manipulated with sterile water.

PMID- 16997124
TI  - Effects of an enamel matrix derivative on human osteoblasts and PDL cells grown
      in organoid cultures.
AB  - OBJECTIVE: The objective of this study was to investigate cellular effects of
      enamel matrix derivative (EMD) in human derived, primary osteoblasts and
      periodontal ligament (PDL) cells grown in organoid cultures. STUDY DESIGN: Cell
      replication was assessed by BrdU-incorporation. [(3)H]-proline incorporation was
      measured to determine the synthesis of proline-containing proteins, such as
      collagen. In addition, calcium accumulation and alkaline-phosphatase-activity
      were quantified. Electron microscopy for morphological analysis was performed.
      RESULTS: Our results showed that EMD enhances BrdU-incorporation in PDL cells and
      osteoblasts. Also, in osteoblast organoid cultures [3H]-proline incorporation was
      3-fold increased (P < .01). Extensive matrix deposition was noted in osteoblast
      cultures by electron microscopy. In osteoblasts, high levels of calcium
      accumulation and alkaline-phosphatase-activity were found. However, EMD did not
      promote mineralization. CONCLUSION: Our results indicate that under organoid
      culture conditions EMD is able to promote the synthesis of proline-containing
      proteins such as collagen but not matrix mineralization of primary human
      osteoblastic cells.

PMID- 16997125
TI  - NK and NKT cells in the rat dental pulp tissues.
AB  - OBJECTIVE: The objective of this study was to elucidate the presence of natural
      killer (NK) and natural killer T (NKT) cells in rat dental pulp. STUDY DESIGN:
      Male Wistar rats (n = 10) were used. The presence of NK and NKT cells in the
      coronal and root pulps of the lower first molars was detected
      immunohistochemically. RESULTS: Infiltration of NK and NKT cells into the normal
      pulp was observed, and most of these cells were located in the coronal pulp
      rather than in the root pulp. The population of NKT cells in the pulp was only
      small compared to the population of NK cells. CONCLUSION: NK and NKT cells are
      present in normal pulp, indicating an important role for the innate immune system
      in the pulp tissues.

PMID- 16997126
TI  - Root canal microbiota of dogs' teeth with periapical lesions induced by two
      different methods.
AB  - OBJECTIVE: The microbial composition was investigated in root canals of dogs'
      teeth with periapical lesions induced by 2 different methods: open versus sealed
      canals. STUDY DESIGN: Teeth from Group I (n = 16) were left open for a week, then
      sealed with composite resin for 120 days. The teeth from Group II (n = 16) were
      left open for the same period. Microbiological samples from the root canals were
      collected and processed by the anaerobic technique for identification and
      counting of microorganisms after establishment of periapical reactions. RESULTS:
      Seventy-four cultivable isolates were recovered in sealed canals (Group I).
      Strict anaerobes accounted for 64.9% of all species isolated, and gram-negative
      microorganisms accounted for 55.4%. Microbial genera most frequently isolated
      were Prevotella, Fusobacterium, Peptostreptococcus, Streptococcus, Enterococcus,
      Clostridium, and Porphyromonas. Statistical analysis by Pearson chi-square or
      Fisher's test revealed positive association between sealed teeth and strict
      anaerobes (P < .05). In open canals (Group II), from a total of 58 cultivable
      isolates, 19% were strict anaerobes and 81% facultative anaerobes, with
      predominance of gram-positive species (75.8%). Genera most frequently isolated
      were Streptococcus, Propionibacterium, Staphylococcus, Neisseria, and Prevotella.
      CONCLUSION: Strict anaerobes were most frequently found in sealed teeth rather
      than in the teeth with canals left exposed to the oral cavity for 4 months.
      Therefore, the method that induced periapical inflammatory lesions by intentional
      oral exposure, followed by tooth sealing, produced root canal microbiota similar
      to the same found in humans.

PMID- 16997127
TI  - Orthotopic expression of human 15-lipoxygenase (LO)-1 in the dorsolateral
      prostate of normal wild-type C57BL/6 mouse causes PIN-like lesions.
AB  - The lipid-peroxidating enzyme, 15-lipoxygenase (LO)-1 and its metabolite, 13-S
      hydroxyoctadecadienoic acid (13-S-HODE), likely contribute to prostate
      tumorigenesis. Thus, this study evaluated adenovirus-mediated overexpression of
      15-LO-1 on normal mouse prostate. Adenovirus expressing either human 15-LO-1
      tagged with green fluorescent protein (GFP) or GFP alone was orthotopically
      injected into the dorsolateral prostates of C57BL/6 mice, three times over the
      course of 60 days. On day 90, pathological changes in prostate tissue were
      assessed by hematoxylin and eosin (H&E) staining. Expression of the proliferation
      marker Ki-67 was evaluated by immunohistochemistry and expression of angiogenesis
      markers were analyzed by an antibody array. Based on the latter study,
      immunoprecipitation analysis was used to measure the effect of 13-S-HODE, with or
      without conditioned media, on fibroblast growth factor-a and b (FGF-a and FGF-b)
      expression in human PrEC (normal prostate epithelial), PrSMC (normal prostate
      smooth muscle) and PrSC (normal prostate stromal) lines. Expression of viral 15
      LO-1-GFP, but not GFP alone, resulted in the development of a prostate
      intraepithelial neoplasia (PIN)-like phenotype with increased expression of Ki
      67. Aberrant 15-LO-1 expression also induced the angiogenic markers FGF-a and FGF
      b. Human PrEC, PrSMC and PrSC lines demonstrated an increase in FGF-b expression
      upon stimulation with 13-S-HODE, which was further increased by the addition of
      conditioned media from the epithelial or smooth muscle cells. Using adenoviral
      mediated 15-LO-1 gene delivery, this study suggests that aberrant 15-LO-1
      overexpression in normal prostate can trigger events leading to prostate
      epithelial and stromal cell proliferation. Thus, our findings demonstrate the
      effectiveness of this viral system for 15-LO-1 expression studies in tissues.

PMID- 16997128
TI  - 15-Hydroxyprostaglandin-dehydrogenase is involved in anti-proliferative effect of
      non-steroidal anti-inflammatory drugs COX-1 inhibitors on a human medullary
      thyroid carcinoma cell line.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin (PG)
      synthesis enzymes, the cyclooxygenases (COX-1 and 2). It is suggested that these
      enzymes are not their only targets. We reported that in tumoral TT cell,
      indomethacin, in vivo and in vitro, decreases proliferation and increases
      activity of 15-hydroxyprostaglandin-dehydrogenase (15-PGDH), the PG catabolism
      key enzyme. Here, we show that the COX-1 inhibitors, selective or not, and
      sulindac sulfone, a non-COX inhibitor, increased 15-PGDH activity and reduced
      PGE2 levels. This increase was negatively correlated to the decrease in cell
      proliferation and suggested that 15-PGDH could be implicated in NSAIDs anti
      proliferative effect. Indeed, the silencing of 15-PGDH expression by RNA
      interference using 15-PGDH specific siRNA enhanced TT cell proliferation and
      abolished the anti-proliferative effect of a representative non-selective
      inhibitor, ibuprofen. Moreover, a specific inhibitor of 15-PGDH activity, CAY
      10397, completely reversed the effect of ibuprofen on proliferation. Consequently
      our results demonstrate that, at least in TT cells, 15-PGDH is implicated in
      proliferation and could be a target for COX-1 inhibitors specific or not. NSAIDs
      defined by their COX inhibition should also be defined by their effect on 15
      PGDH.

PMID- 16997129
TI  - Activation of prostaglandin E receptor EP4 subtype suppresses food intake in
      mice.
AB  - Prostaglandin (PG) E2, a bioactive lipid produced in the brains of various
      mammals, decreases food intake after central administration. We examined which of
      four distinct subtypes of PGE2 receptors (EP1-EP4) mediated the anorexigenic
      action of PGE2 using highly selective ligands. PGE2 at a dose of 0.1-10
      nmol/mouse decreased food intake after intracerebroventricular (i.c.v.)
      administration in a dose-dependent manner in fasted mice. A centrally
      administered EP4 agonist, ONO-AE1-329 at a dose of 1-10 nmol/mouse mimicked the
      anorexigenic action by PGE2. The anorexigenic action of PGE2 or EP4 agonist was
      ameliorated by EP4 antagonist ONO-AE3-208 at a dose of 10 nmol/mouse. Thus,
      activation of PGE2-EP4 signaling in the central nervous system suppresses food
      intake. The EP4 agonist at a dose of 10 nmol/mouse delayed gastric emptying and
      elevated blood glucose.

PMID- 16997130
TI  - The effect of progesterone on oxytocin-stimulated intracellular mobilization of
      Ca2+ and prostaglandin E2 and F2alpha secretion from porcine myometrial cells.
AB  - Our past studies have shown that porcine myometrium produce prostaglandins (PG)
      during luteolysis and early pregnancy and that oxytocin (OT) and its receptor
      (OTr) support myometrial secretion of prostaglandins E2 and F2alpha (PGE2 and
      PGF2alpha) during luteolysis. This study investigates the role of intracellular
      Ca2+ [Ca2+]i as a mediator of OT effects on PG secretion from isolated myometrial
      cells in the presence or absence of progesterone (P4). Basal [Ca2+]i was similar
      in myometrial cells from cyclic and pregnant pigs (days 14-16). OT (10(-7)M)
      increased [Ca2+]i in myometrial cells of cyclic and pregnant pigs, although this
      effect was delayed in myometrium from pregnant females. After pre-incubation of
      the myocytes with P4 (10(-5)M) the influence of OT on [Ca2+]i)was delayed during
      luteolysis and inhibited during pregnancy. Myometrial cells in culture produce
      more PGE2 than PGF2alpha regardless of reproductive state of the female. OT (10(
      7)M) increased PGE2 secretion after 6 and 12 h incubation for the tissue
      harvested during luteolysis and after 12 h incubation when myometrium from gravid
      females was used. In the presence of P4 (10(-5)M), the stimulatory effect of OT
      on PG secretion was diminished. IN CONCLUSION: (1) porcine myometrial cells in
      culture secrete PG preferentially during early pregnancy and produce more PGE2
      than PGF2alpha, (2) OT controls myometrial PGF2alpha secretion during luteolysis,
      (3) release of [Ca2+]i is associated with the influence of OT on PG secretion,
      and (4) the effects of OT on PG secretion and Ca2+ accumulation are delayed by P4
      during luteolysis and completely inhibited by P4 during pregnancy.

PMID- 16997131
TI  - Prostaglandin involvement in follicle-stimulating hormone-induced proliferation
      of granulosa cells from chicken prehierarchical follicles.
AB  - The aim of the present study was to evaluate the role of prostaglandin (PG) on
      proliferation of granulosa cells from prehierarchical small yellow follicles
      (SYF) of buff laying hens. The granulosa layers were separated by mechanic method
      and dispersed into single cells. After 16 h pre-incubation in 0.5% FCS medium,
      the medium was replaced with serum-free medium, which was supplemented with 10
      microg/ml insulin, 5 microg/ml transferrin and 3 x 10(-8)M selenite. Cells were
      challenged with PGE1 and FSH for 24 h and then assessed for proliferation. The
      results showed that PGE(1) (0.1-10 ng/ml) had a similar proliferating effect as
      FSH on granulosa cells, and these stimulating effects were restrained by the PGE
      receptor antagonist SC19220 at 10(-7) to 10(-5)M. Prostaglandin synthase
      antagonist indomethacin (10(-7) to 10(-5)M) suppressed FSH-induced increase in
      the number of granulosa cells in a dose-dependent manner. Downstream activation
      of protein kinase A by forskolin-activated adenylate cyclase resulted in elevated
      proliferation of granulosa cells, an effect unobserved by phorbol-12-myristrate
      13-acetate-activated protein kinase C. In addition, PGE1-stimulated proliferation
      of granulosa cells was hindered by H89 (PKA inhibitor) but not by H7 (PKC
      inhibitor). Furthermore, the proliferating cell nuclear antigen labeling index
      (PCNA-LI) of granulosa cells displayed similar changes with the number of cells.
      These results indicated that PGE1 promoted the proliferation of granulosa cells
      from SYF and was also involved in mediating FSH-stimulated intracellular PKA
      signal transduction.

PMID- 16997132
TI  - Cyclooxygenase-2 directly regulates gene expression of P450 Cyp19 aromatase
      promoter regions pII, pI.3 and pI.7 and estradiol production in human breast
      tumor cells.
AB  - The present studies evaluated the direct effects of the presence of human
      cyclooxygenase-2 (Cox-2) on gene expression of specific promoter regions of the
      P450 Cyp19 enzyme aromatase enzyme and its product, estradiol, in Cox-2 null
      estrogen-dependent MCF-7 breast tumor cells and in a stable clone of MCF-7 cells
      containing transfected Cox-2 cDNA, designated as MCF-7/Cox-2 Clone 10. Clone 10
      human breast tumor cells have significantly increased gene expression of total
      mRNA of the P450 Cyp19 enzyme aromatase, with high levels of gene expression of
      specific aromatase promoter (p) regions pII, pI.3, and p1.7, with no significant
      change in mRNA levels of p1.4. Clone 10 human breast tumor cells produced
      significantly increased amounts of both prostaglandin E2 (PGE2) derived from Cox
      2 enzyme activity and estradiol derived from aromatase enzyme activity (p<0.01),
      compared to MCF-7/vector control cells. The greatest inhibition of PGE2 or
      estradiol production was observed by the combination of the selective Cox-2
      inhibitor celecoxib (25 microM) and the aromatase inhibitor, formestane (10nM)
      (p<0.01). The greatest anti-proliferative effect in Cox-2 null MCF-7/vector
      control cells was observed with the combination of 25 microM celecoxib and 10nM
      formestane but not with 10 microM celecoxib, suggesting that there are Cox-2
      independent mechanisms involved in the anti-proliferative effect of this agent at
      doses greater than 10 microM. Celecoxib (25 microM) also significantly inhibited
      proliferation of MCF-7/Cox-2 Clone 10 human breast tumor cells, with no further
      anti-proliferative activity with the addition of 10 nM formestane observed at
      either 24 or 48 h of treatment. These studies demonstrate that Cox-2 directly
      regulates gene expression of specific aromatase promoter regions and regulates
      aromatase enzyme activity. Agents that inhibit Cox-2 or block the biological
      effects of PGE2 may be useful in significantly limiting aromatase activity and
      proliferation of human breast tumor cells regardless of the presence of Cox-2. In
      addition, the unique human breast tumor cell model used in these studies may be a
      useful tool in identifying the spectrum of activities of agents that block the
      biological effects of PGE2 and estradiol.

PMID- 16997133
TI  - Retrograde and local destination transfer of uterine prostaglandin E2 in early
      pregnant sow and its physiological consequences.
AB  - The local destination transfer of prostaglandin E2 (PGE2) from the uterine lymph
      to arterial blood supplying the ovary and its retrograde transfer to arterial
      blood supplying the uterine horn and the effect of additional delivery of PGE2
      into the ovary on the secretion of steroid hormones was studied in early pregnant
      gilts. The injection of PGE2 under the perimetrium caused an increase (P<0.001)
      in PGE2 concentration in both uterine venous effluent and ovarian and uterine
      arterial blood. The infusion of PGE2 into the ovarian artery increased the
      concentration of progesterone in ovarian venous blood on day 13 of pregnancy
      during (P<0.05) and after (P<0.001) infusion, and on day 14 of pregnancy after
      infusion (P<0.01). In conclusion, local destination transfer of PGE2 from uterine
      lymph and venous blood to the ovary may affect luteal function, and retrograde
      transfer of PGE2 to the arterial blood supplying the uterus may contribute to the
      prevention of regressive changes of the endometrium in early pregnant gilts.

PMID- 16997135
TI  - Measure, mine, model, and manipulate: the future for HTS and chemoinformatics?

PMID- 16997134
TI  - Purification of prostaglandin D synthase by ceramic- and size exclusion
      chromatography.
AB  - Prostaglandin D synthase (L-PGDS) is a major glycosylated polypeptide in
      cerebrospinal fluid (CSF). The overexpression of L-PGDS in inflamed bovine
      mammary glands indicates its role as biomarker. No diagnostic tool for the
      quantitative detection of L-PGDS in cows has been reported. Immunometric ELISA
      tests might help to identify inflamed bovine tissue. The isolation of pure bovine
      L-PGDS, which is required for the generation of monoclonal antibodies, is an
      important prerequisite for a diagnostic ELISA test. Our goal was to identify a
      suitable technique to generate pure L-PGDS from bovine substrates. In the present
      study a two-step method for the purification of bovine CSF using ceramic
      hydroxyapatite chromatography followed by size exclusion chromatography is
      described. Subsequently, the identification of bovine L-PGDS was demonstrated by
      Western blot analysis and the high grade of the pure product was shown by 2-D
      PAGE. The yield of purified L-PGDS was 6.8 mg/l bovine CSF. L-PGDS from bovine
      CSF is shown to consist of multiple isoforms identical in molecular mass and pI
      values to those in previously described secretions of inflamed bovine mammary
      glands. In addition, the method was successfully applied to the purification of L
      PGDS from human CSF.

PMID- 16997136
TI  - Leukocyte navigation mechanisms as targets in airway diseases.
AB  - Respiratory diseases, including asthma and chronic obstructive pulmonary disease,
      are among the most significant diseases in terms of their disabling effects and
      healthcare burden. A characteristic feature of almost all respiratory diseases is
      the accumulation and activation of inflammatory leukocytes in the lung or airway.
      Recent advances in the understanding of the molecules and intracellular
      signalling events controlling these processes are now translating to new
      therapeutic entities. In this article, the process of leukocyte accumulation is
      summarized, together with the preclinical and clinical evidence supporting the
      utility of the individual components of this process as targets for disease
      therapy.

PMID- 16997137
TI  - Chemogenomics: structuring the drug discovery process to gene families.
AB  - In the post-genomic era, if all proteins in a gene family can putatively be
      identified, how can drug discovery effectively tackle so many novel targets that
      might lack structural and small-molecule inhibitory data? In response,
      chemogenomics, a new approach that guides drug discovery based on gene families,
      has been developed. By integrating all information available within a protein
      family (sequence, SAR data, protein structure), chemogenomics can efficiently
      enable cross-SAR exploitation, directed compound selection and early
      identification of optimum selectivity panel members. This review examines recent
      developments in chemogenomics technologies and illustrates their predictive
      capabilities with successful examples from two of the major protein families:
      protein kinases and G-protein-coupled receptors.

PMID- 16997138
TI  - High-content screening moves to the front of the line.
AB  - High-content screening (HCS) has been used in late-stage drug discovery for a
      decade. In the past few years, technological advances have expanded the role of
      HCS into the early stages of drug discovery, including high-throughput screening
      and hit-to-lead studies. More recently, computational advances in image analysis
      and technological advancements in general cell biology have extended the utility
      of HCS into target validation and basic biological studies, including RNAi
      screening. The use of HCS in target validation is expanding the work that can be
      done at this stage, especially the range of targets that can be characterized,
      and putting it into a more biological context.

PMID- 16997139
TI  - Shape Signatures: speeding up computer aided drug discovery.
AB  - Identifying potential lead molecules is becoming a more automated process. We
      review Shape Signatures, a tool that is effective and easy to use compared with
      most computer aided drug design techniques. Laboratory researchers can apply this
      in silico technique cost-effectively without the need for specialized computer
      backgrounds. Identifying a potential lead molecule requires database screening,
      and this becomes rate-limiting once the database becomes too large. The use of
      Shape Signatures eliminates this concern and offers molecule screening rates that
      are in advance of any currently available method. Shape Signatures provides a
      conduit for researchers to conduct rapid identification of potential active
      molecules, and studies with this tool can be initiated with only one bioactive
      lead or receptor site.

PMID- 16997140
TI  - Is the oral route possible for peptide and protein drug delivery?
AB  - Oral delivery of peptides and proteins remains an attractive alternative to
      parenteral delivery and has challenged various attempts at delivery development.
      Incorporation of new tools into the delivery systems that can raise membrane
      permeability of macromolecules is essential to attain high oral bioavailability
      that is acceptable in clinical applications. In developing oral protein delivery
      systems with high bioavailability, three practical approaches might be most
      helpful: (1) modification of the physicochemical properties of macromolecules;
      (2) addition of novel function to macromolecules; or (3) use of improved delivery
      carriers. Clearly, it is essential that these approaches maintain the biological
      activity of the proteins.

PMID- 16997141
TI  - Ribosome-display technology: applications for directed evolution of functional
      proteins.
AB  - In vitro display technologies, especially ribosome display, are valuable tools
      for many applications. In this paper, ribosome display technology and its
      applications for directed evolution of functional proteins will be reviewed.
      Ribosome display has great potential for directed evolution of protein stability
      and affinity, the generation of high-quality libraries by in vitro preselection,
      the selection of enzymatic activities, and the display of cDNA and random-peptide
      libraries. Ribosome display is carried out fully in vitro, which overcomes some
      of the limitations of cell-based display systems. We anticipate that ribosome
      display will have a great impact on applications in biotechnology, medicine and
      proteomics.

PMID- 16997142
TI  - The therapeutic potential of the calpain family: new aspects.
AB  - The calpain family is a group of cysteine proteases unique in their dependency on
      calcium to attain functionally active forms. Calpains are involved in a wide
      range of cellular calcium-regulated functions, including signal transduction,
      cell proliferation and differentiation, and apoptosis. Moreover, altered calpain
      activity has been observed in several human diseases. Specific calpain inhibitors
      hold promise for the treatment of neuromuscular and neurodegenerative diseases in
      which calpains have been shown to be upregulated (e.g. Parkinson's disease and
      Duchenne muscular dystrophy). Conversely, calpain activators could be a useful
      approach for those diseases where reduced calpain activity has been observed,
      such as type 2 diabetes or metabolic syndrome.

PMID- 16997143
TI  - Canonical transient receptor potential channels in disease: targets for novel
      drug therapy?
AB  - The canonical transient receptor potential (TRPC) channels constitute one of the
      three major families within the large transient receptor potential (TRP)
      superfamily. TRPC channels are the closest mammalian homologues of Drosophila
      TRP, the light-activated channel in Drosophila photoreceptor cells. All TRPC
      channels (TRPC1-7) are activated via phospholipase-C-coupled receptors and were,
      therefore, proposed to encode elusive native receptor-activated cation channels
      in many cell types. A physiological role has been established for all of the
      known TRPC channels, including the control of vascular tone (TRPC1, TRPC4 and
      TRPC6) or lymphocyte activation, which is essential for immune competence (TRPC1
      and TRPC3). The emergence of TRPC channels in controlling a variety of biological
      functions offers new and promising targets for drug development.

PMID- 16997144
TI  - Clearance of amyloid-beta in Alzheimer's disease: progress, problems and
      perspectives.
AB  - Alzheimer's disease (AD) is the most common form of senile dementia and the
      fourth highest cause of disability and death in the elderly. Amyloid-beta (Abeta)
      has been widely implicated in the etiology of AD. Several mechanisms have been
      proposed for Abeta clearance, including receptor-mediated Abeta transport across
      the blood-brain barrier and enzyme-mediated Abeta degradation. Moreover, pre
      existing immune responses to Abeta might also be involved in Abeta clearance. In
      AD, such mechanisms appear to have become impaired. Recently, therapeutic
      approaches for Abeta clearance, targeting immunotherapy and molecules binding
      Abeta, have been developed. In this review, we discuss recent progress and
      problems with respect to Abeta clearance mechanisms and propose strategies for
      the development of therapeutics targeting Abeta clearance.

PMID- 16997145
TI  - Inhibitors of de novo folate enzymes in Plasmodium falciparum.
AB  - Antifolates, inhibitors of folate synthesis or folate conversion, are used for
      malaria treatment. They are developed as synergistic combinations of inhibitors
      of dihydrofolate reductase (DHFR) and of dihydropteroate synthase (DHPS). DHPS
      inhibitors are sulfur-based drugs, analogs of sulfanilamide. These compounds
      compete with para-aminobenzoic acid in the active site of DHPS. The discovery of
      new antifolates is based on the identification of DHFR inhibitors; little work
      has been done on sulfur-based drugs because of their toxicity. As a result, only
      a few sulfur-based drugs are available. In this review, the hypothesis that
      compounds that compete with pteridine derivatives in active sites of de novo
      folate enzymes can be used as synergizers of DHFR inhibitors is discussed. If
      correct, this could lead to the identification of a new family of synergizers of
      DHFR inhibitors.

PMID- 16997146
TI  - Regulating biopharmaceuticals under CDER versus CBER: an insider's perspective.
AB  - The FDA has recently transferred jurisdiction for the regulation of certain
      biopharmaceuticals from the Center for Biologics, Evaluation and Research to the
      Center for Drugs, Evaluation and Research, where they will be reviewed in the
      same FDA divisions as are traditional pharmaceutical agents. With this transfer,
      sponsors of investigational biopharmaceuticals should expect changes in the
      regulatory requirements the FDA imposes on the clinical development plans,
      including an increase in the size and number of pivotal studies; more consistent
      requirements for conducting preclinical tests in two animal species; increased
      emphasis on organ structure and function as components of primary endpoints; more
      emphasis on characterizing dose-ranging and pharmacology; more intense
      scrutinizing of product advertising; and decreased direct communication with the
      review team.

PMID- 16997147
TI  - New therapeutics that treat rheumatoid arthritis by blocking T-cell activation.
AB  - Despite the recent introduction of several new biological products, there remains
      a significant unmet medical need in rheumatoid arthritis. A focus on the aberrant
      activation of autoimmune T cells, which is integral to pathogenesis, is a
      promising approach involved in several of these new therapies. In choosing a
      molecular target for the modification of T-cell function, it is argued in this
      article, that within co-stimulatory pathways, CD80 could have a more compelling
      rationale than CD86. Data are presented showing that CD80-mediated T-cell
      activation can be inhibited using a small-molecule antagonist, which offers the
      potential to prevent the inflammatory process leading to joint destruction.

PMID- 16997150
TI  - Gastric cancer: global pattern of the disease and an overview of environmental
      risk factors.
AB  - This first part of this chapter looks at the worldwide burden of gastric cancer
      at the beginning of the 21st century and summarises available population-based
      routine data that describes the variation in incidence of the disease in relation
      to age, sex, geography and time period. Consideration is also given to the
      differences in the descriptive epidemiology of gastric cancer arising in the
      proximal cardia region of the stomach. In the second part of the chapter, a brief
      review of the main identified environmental risk factors is conducted drawing,
      where available, on published systematic literature overviews and meta-analyses.
      Evidence relating the aetiology of gastric cancer to Helicobacter pylori
      infection, dietary factors, smoking, occupation, physical activity and
      anthropometry is presented.

PMID- 16997151
TI  - Pathology and molecular biology of gastric cancer.
AB  - Several attempts to classify gastric cancer (GCA) have been made over the past
      decades. Most successful, and widely used, is the classification by Lauren, which
      distinguishes, by microscopical morphology alone, two main cancer pathogeneses,
      diffuse (DGCA) and intestinal (IGCA) subtypes, which appear clearly as dissimilar
      clinical and epidemiological entities. Here we review the main differences in
      epidemiology, histopathology, and molecular pathology of the two main subtypes of
      gastric carcinomas based on Lauren classification. In clinical practice, however,
      clinical staging, particularly in predicting the survival, still remains superior
      to all classifications of gastric cancer independent of cancer type. The
      existence of local precursor lesions or conditions of IGCA tumours, i.e.
      Helicobacter pylori gastritis, atrophic gastritis (AG), intestinal metaplasia
      (IM), adenoma, dysplasia, and intramucosal neoplasia, is firmly established. The
      links of DGCA with intestinal-type epithelium, AG or IM are poor, or do not
      exist. So far, H. pylori gastritis is the only universal precursor condition for
      DGCA. It implies that AG and achlorhydria are of minor significance and
      infrequent in the development of DGCA but are important steps in that of IGCA.
      Despite an increasing body of data, the overall view on molecular pathology of
      GCA remains fragmentary. No consistent differences in the molecular pathology of
      GCA subtypes to meet the Lauren classification have been established. With the
      exception of TP53, no gene mutation occurring regularly in both histological
      types of GCA has been reported. Chromosomal aberrations and loss of
      heterozygosity seem to be non-specific and do not follow any consistent route in
      the progression of GCA. Microsatellite instability is more commonly found in IGCA
      than in DGCA. The present epigenetic data suggest that most of the decrease (or
      loss) of gene expression may be explained by promoter hypermethylation which is
      more often found in IGCA. In DGCA specific genes such as CDH1 are more often
      hypermethylated. Compared with GCA, in premalignant condition lesions gene
      mutations and chromosomal aberrations are infrequent. Epigenetic dysregulation
      might also represent a major mechanism for altered gene expression in
      premalignant stages in gastric carcinogenesis.

PMID- 16997152
TI  - Role of host genes in sporadic gastric cancer.
AB  - Gastric cancer remains a major health problem particularly in the developing
      world. Helicobacter pylori (H. pylori) infection is the most recognised
      aetiological risk factor for this malignancy. The infection causes a chronic
      gastritis that is the precursor to all the pathophysiological abnormalities
      characteristic of gastric carcinogenesis. Genetic polymorphisms have emerged in
      recent years as important determinants of disease susceptibility and severity. In
      the case of H. pylori-induced gastric cancer, host genetic polymorphisms play an
      important role both in the precancerous stages and in the transition to cancer.
      In particular, polymorphic genes of the adaptive and innate immune response are
      involved in all stages of the neoplastic process. This field is rapidly expanding
      and many other genetic determinants are currently being defined. The ultimate
      value of host genetics should be in understanding the pathogenesis of the
      disease, which would offer a true opportunity to defeat this global killer.

PMID- 16997153
TI  - Cancer of the gastric cardia.
AB  - Current evidence indicates that cardia cancers are of at least two distinct and
      disparate aetiologies. One type resembles cancer of the more distal stomach (Type
      A), being a consequence of atrophic gastritis due to Helicobacter pylori
      infection or more rarely autoimmune atrophic gastritis. Another type (Type B)
      resembles oesophageal adenocarcinoma and is likely to be a consequence of short
      segment gastro-oesophageal reflux disease. The two cancers are themselves
      indistinguishable but examination of the gastric phenotype indicates the
      aetiology: Type A occurring in patients with evidence of atrophic gastritis
      whereas Type B occurs in subjects with healthy acid secreting stomachs. In
      subjects with healthy acid secreting stomachs the cardia has a specific luminal
      chemistry remaining highly acidic and unbuffered following a meal and having very
      active nitrosative chemistry due to the acidification of nitrite in saliva. This
      luminal chemistry may contribute to the high incidence of metaplasia and
      neoplasia at this anatomical site.

PMID- 16997154
TI  - Symptoms and diagnosis of gastric cancer at early curable stage.
AB  - Five-year survival of gastric cancer is 10% in Western countries compared with
      over 50% in Japan. This is because the disease is not identified in the West
      until later in its evolution. T1 cancer has an excellent prognosis, but most of
      the patients either have no symptoms or complain of long-standing, non-specific
      dyspepsia; alarm symptoms, when identified, usually indicate that the cancer is
      already inoperable. Early gastric cancer is infrequently diagnosed in the West
      because the low prevalence of gastric cancer means that endoscopists do not
      search with the same diligence as they do in Japan. A further barrier is the
      widespread prescription of proton pump inhibitors that heal malignant ulcers and
      diminish symptoms, thus rendering them more difficult to identify clinically and
      endoscopically. An improvement in diagnosis may be achieved by newer endoscopy
      technology which enables cancers to be identified more easily, or by an
      inexpensive screening test to select patients with extensive gastric atrophy,
      thereby identifying those at risk who can then be screened endoscopically.

PMID- 16997155
TI  - Can gastric cancer be prevented by Helicobacter pylori eradication?
AB  - Helicobacter pylori infection always causes chronic gastritis and triggers
      several gastroduodenal pathologies ranging from peptic ulcer disease to gastric
      cancer. It is well established that H. pylori eradication decreases the incidence
      of gastroduodenal ulcer and its recurrence. However, despite being accepted as
      the critical risk factor for gastric cancer, there is no conclusive evidence that
      H. pylori eradication decreases the incidence of gastric cancer. Bacterial
      virulence characteristics, as well as genetic predisposition of the host in
      conjunction with certain environmental conditions, are the major factors which
      influence the development of gastric cancer. Preclinical and clinical data
      suggest that reversibility of precancerous lesions (atrophic gastritis and
      intestinal metaplasia) is possible in some patients after H. pylori eradication.
      Since neoplastic lesions do not progress - or even regress in some cases - after
      H. pylori eradication, eradication therapy should be considered even in patients
      with precancerous lesions. Nonetheless, progression of atrophic gastritis and
      intestinal metaplasia into cancer has been also demonstrated in patients after H.
      pylori eradication, suggesting that there might be a point of no return where
      genetic changes have already happened and are irreversible despite elimination of
      the triggering carcinogen (H. pylori). At the present time the clinical decision
      to treat a patient is based on established risk profiles. A general screen-and
      treat policy, although desirable, currently awaits a less complex treatment
      regimen.

PMID- 16997156
TI  - Familial gastric cancer - aetiology and pathogenesis.
AB  - Gastric cancer is the second most common cause of cancer death worldwide. It is
      estimated that 5-10% of gastric cancer cases have a familial association;
      however, knowledge concerning the genetic predisposition to familial gastric
      cancer is currently limited. In this chapter we discuss what is known about the
      aetiology and pathogenesis of both the diffuse and intestinal forms of familial
      gastric cancer. We focus particularly on hereditary diffuse gastric cancer
      because the discovery of germ-line E-cadherin mutations in a number of affected
      families has opened the prospect of identifying gene carriers, with implications
      for clinical management. The interplay of other conventional risk factors, such
      as Helicobacter pylori infection, with genetic factors is also discussed. It is
      hoped that understanding the genetic basis for familial gastric cancer will
      facilitate the development of clinically useful screening and preventative
      procedures.

PMID- 16997157
TI  - Familial gastric cancer - clinical management.
AB  - The clinical management of familial gastric cancer is the same as that for
      sporadic gastric cancer at the current time. As the causative mutations for these
      cases are identified this should lead to the development of specific treatments
      which target the molecular abnormality. The only germline mutations identified so
      far occur within the E-cadherin gene (CDHI) and they account for approximately
      30% of familial gastric cancer cases. When index patients fulfilling the clinical
      criteria for hereditary diffuse gastric cancer syndrome have a CDHI mutation
      identified then genetic testing of asymptomatic relatives should be considered.
      The clinical sequelae of testing positive for such a mutation are profound and
      therefore it is essential that counselling is given prior to genetic testing. The
      management options are surveillance endoscopy and prophylactic gastrectomy. In
      this chapter the practicalities of genetic testing are discussed as well as the
      pros and cons of the two management options. It is essential that experience of
      these rare families is pooled so that surveillance and treatment can be optimised
      in the future.

PMID- 16997158
TI  - Detection and treatment of early cancer in high-risk populations.
AB  - In this paper we describe how to more efficiently detect and treat early gastric
      cancer (EGC) in high-risk populations. For detection, we first assess the value
      of known risk factors from the viewpoint of availability for cancer screening.
      Serum pepsinogen appears to be the most useful and realistic of the factors
      examined, although its adequacy needs to be assessed in high-risk populations
      other than those in Japan. Helicobacter pylori infection is known to be a
      universal risk factor (or gastric carcinogen), and several interventional studies
      have recently shown positive results. However, H. pylori infection can be
      eradicated from at-risk populations, thereby decreasing its availability for
      cancer screening. Smokers are thought to be at risk epidemiologically, but the
      efficacy of screening in this population has yet to be elucidated, and further
      studies are warranted. Gender and aging can be risk factors in Japanese
      populations; male gender and old age are predominant in the intestinal type of
      carcinoma which is dominant in Japan, although this is not the case in the West.
      As for early diagnosis of cancer, only endoscopy can be commonly used for the
      detection of gastritis-like EGC, seen as a faint mucosal irregularity or
      discoloration. To make early diagnosis more accurate, it is indispensable to
      carry out detailed endoscopy together with careful scrutiny of the mucosa using
      dye-spraying techniques. The remarkable progress of early diagnosis in Japan
      prompted the endoscopic treatment for less invasive EGCs. The first success was
      with endoscopic mucosal resection (EMR). Although convenient, its therapeutic
      efficacy is inadequate, particularly for larger lesions. Endoscopic submucosal
      dissection (ESD) has no limitation on resection size and is expected to replace
      surgery, although it needs a high level of skill and there are several technical
      problems to be solved.

PMID- 16997159
TI  - The role of surgery in patients with advanced gastric cancer.
AB  - Surgery remains the mainstay of treatment with curative intent for established
      gastric cancer. Patient selection is critical to achieving satisfactory outcomes,
      and involves careful assessment of both patient fitness and disease stage.
      Staging techniques have multiplied and become much more sensitive in recent
      years. Current best practice involves a combination of spiral CT scan, Endoscopic
      ultrasound, PET scanning and laparoscopy. Only a minority of patients progress to
      potentially curative surgery after staging and fitness assessment in Western
      centres. Conventional treatment involves a distal subtotal gastrectomy or total
      gastrectomy depending on the site of the lesion. Innovative techniques include
      the Merendino operation, and pylorus and nerve sparing gastrectomies for earlier
      stage disease in the proximal and distal stomach, respectively. There is evidence
      of nutritional and quality of life benefit in the first 2 years after surgery
      from formation of a gastric substitute reservoir. Laparoscopic resection is well
      established in Japan and is developing rapidly elsewhere but its role and
      outcomes are not yet well defined. Radical lymph node dissection remains
      controversial: randomised trial evidence of overall benefit is lacking, but
      expert series have produced excellent results, and there are indications of a sub
      group benefit for patients with stage II and III disease. The increased morbidity
      and mortality associated with radical dissection appear to be largely
      attributable to pancreatic and splenic resection together with limitations in
      Unit expertise. Surgical palliation has become less important in recent years as
      interventional radiology and endoscopy techniques have been developed for the
      same purposes. Overall mortality and survival results have improved dramatically
      over the last 20 years, but interpretation of these figures is made difficult by
      major changes in staging and case selection. The chances of long-term survival
      are, however, clearly much greater, and those of peri-operative death much less
      for an individual patient accepted for surgery in 2006 than they would have been
      in 1986.

PMID- 16997160
TI  - The role of chemotherapy in patients with established gastric cancer.
AB  - Chemotherapy significantly improves survival in comparison to best supportive
      care in patients with metastasised gastric cancer. In patients for whom a three
      drug-combination is considered as the treatment of choice, ECF (epirubicin,
      cisplatin and 5-FU as a continuous infusion) should be regarded as standard of
      care. However, results for ECF have been challenged by the recently presented
      REAL-2-trial, which demonstrated a significant survival benefit for EOX
      (epirubicin, oxaliplatin, capecitabine) over ECF. Adjuvant 5-FU-based
      chemoradiation should be discussed in patients with inadequate lymphadenectomy,
      but is not internationally accepted as standard of care: whether patients with
      adequate lymhphadenectomy benefit from adjuvant chemoradiotherapy is currently
      unclear. According to the results of the UK MAGIC trial, perioperative treatment
      with ECF (3 cycles prior to and post surgery) results in a significantly reduced
      risk of death for patients with resectable gastric cancer as compared to surgery
      alone. Neo-adjuvant chemotherapy has the ability to downsize gastric tumours and
      appears to improve R0-resection rates, but its potential to improve overall
      survival is still unclear.

PMID- 16997161
TI  - Oesophageal adenocarcinoma.

PMID- 16997162
TI  - Etiology and risk factors for oesophageal adenocarcinoma: possibilities for
      chemoprophylaxis?
AB  - The rapid increase in the incidence of oesophageal adenocarcinoma, particularly
      among white males, seems to be a true increase occurring in many parts of the
      industrialised world during the last few decades. Some main risk factors have
      been established: i.e. Barrett's oesophagus, gastrooesophageal reflux, high body
      mass, male sex, tobacco smoking, and high dietary intake of fruit and vegetables.
      Several other potential risk factors have been studied for which the evidence is
      less clear, including medications that relax the lower oesophageal sphincter or
      diets high in fat or low in nutrients from plant foods. Other factors have been
      found to be possibly inversely linked with the risk of oesophageal
      adenocarcinoma, including infection with Helicobacter pylori and anti
      inflammatory drugs (such as aspirin and other non-steroidal anti-inflammatory
      drugs, including cyclo-oxygenase inhibitors). The methodological problem of
      'confounding by indication' makes it difficult to interpret the results of anti
      inflammatory drugs, and currently such medication cannot be recommended for the
      prevention of oesophageal adenocarcinoma. Similarly, since there is no strong
      evidence of a preventive effect of medical or surgical antireflux therapy with
      regard to risk of oesophageal adenocarcinoma, such therapy cannot be recommended
      in the prevention of this cancer. Although some of the known risk factors might
      contribute to the increasing incidence of oesophageal adenocarcinoma, the
      explanation that can entirely explain this striking trend remains to be
      identified. Oesophageal adenocarcinoma is a highly deadly cancer, but the overall
      prognosis and the prognosis after oesophageal cancer surgery has improved during
      recent years.

PMID- 16997163
TI  - Molecular biology of Barrett's cancer.
AB  - Oesophageal adenocarcinoma (OA) remains one of the more deadly forms of gastro
      intestinal cancer with a mortality rate exceeding 90%. The incidence of OA
      remains unabated and has a reported fivefold increase since 1970 [Pera M, Cameron
      AJ, Trastek VF, Carpenter HA & Zinsmeister AR. Increasing incidence of
      adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology
      1993; 104(2): 510-513]. Gastro-oesophageal reflux disease and its sequelae,
      Barrett's oesophagus, is one of the principle risk factors in the development of
      OA, with a 30-fold increased risk in Barrett's patients compared with the general
      population [Tytgat GNJ. Does endoscopic surveillance in esophageal columnar
      metaplasia (Barrett's-Esophagus) have any real value. Endoscopy 1995; 27(1): 19
      26]. OA is thought to be a microcosm of evolution, developing sequentially along
      the metaplasia-dysplasia-adenocarcinoma sequence. Progression is attributed to a
      series of genetic and epigenetic events that ultimately allow for clonal
      selection of Barrett's cells via subversion of intrinsic control mechanisms
      regulating cellular proliferation and/or apoptosis. This review will describe the
      current suppositions of the mechanisms behind the selection and subsequent
      expansion of Barrett's clones, and focus on some of the principle hallmarks
      associated with this transition.

PMID- 16997164
TI  - The rationale for screening and surveillance of Barrett's metaplasia.
AB  - Oesophageal adenocarcinoma is a rare cancer; however, it is the most rapidly
      increasing cancer in the western world. Barrett's oesophagus is the only
      recognised precursor and is associated with the majority of cases of
      adenocarcinoma. The role of screening and surveillance in patients with Barrett's
      oesophagus remains controversial. There is insufficient evidence to show that
      screening improves survival and is cost-effective. Indirect evidence suggests
      that patients diagnosed with cancer while undergoing surveillance endoscopy are
      diagnosed at an earlier stage and have an improved survival. The problems with
      current surveillance techniques include lack of data on natural history of
      Barrett's oesophagus, test invasiveness, costs, lack of standardisation and
      validation of biopsy and treatment protocols, and endoscopy intervals. The use of
      novel endoscopic techniques and biomarkers combined with better identification of
      high-risk groups could make screening and surveillance a cost-effective practice
      in the future.

PMID- 16997165
TI  - The endoscopic diagnosis and staging of oesophageal adenocarcinoma.
AB  - The endoscopic evaluation of patients with oesophageal adenocarcinoma does not
      only serve the purpose of diagnosing the lesion and obtaining biopsies for
      histological evaluation: a systematic description of advanced lesions is also
      required to guide further therapeutic decisions. New endoscopic imaging
      modalities hold the promise of better endoscopic detection of early cancer and
      its precursor lesions in Barrett's oesophagus. Video-autofluorescence and narrow
      band imaging are the most promising techniques in this respect. The former may be
      used as a 'red flag' technique, identifying lesions that remain occult with white
      light endoscopy; the latter may be used as a targeted imaging technique, allowing
      for detailed inspection of the mucosal and vascular patterns that may help to
      distinguish early neoplasia from non-dysplastic tissue. Currently, prototypes are
      under investigation that combine high-resolution endoscopy, narrow band imaging
      and video-autofluorescence in one endoscopy system. Endoscopic ultrasonography
      (EUS) is superior to any other imaging modality in the assessment of local tumour
      infiltration of oesophageal adenocarcinoma and locoregional lymph nodes status.
      EUS allows for the identification of patients with advanced disease who are
      unlikely to benefit from attempts at curative surgery and in whom a conservative
      palliative treatment is indicated. EUS may also play a role in the selection of
      patients for local endoscopic treatment of early oesophageal cancer. EUS guided
      fine needle aspiration (EUS-FNA) of locoregional lymph nodes is safe with a high
      sensitivity and an impeccable specificity for assessment of malignant
      involvement. The indications for EUS-FNA of lymph nodes, however, depend on local
      treatment protocols: caeliac nodes (M1a) and lymph nodes located at or above the
      subcarinal area are the most widely used indications. In addition, it may be
      important if the choice for specific treatment protocols (e.g. neoadjuvant
      chemoradiotherapy) depends on lymph node status.

PMID- 16997166
TI  - The role of endoscopic resection and ablation therapy for early lesions.
AB  - Endoscopic resection (ER) has gained more and more importance in the treatment of
      early neoplastic lesions in Barrett's oesophagus over the last few years. The
      choice of the different available techniques depends on the site, the macroscopic
      type of the tumour and the personal experience of the endoscopist. The 'suck-and
      cut' technique with ligation device or cap should be favoured to normal strip
      biopsy in the oesophagus because of the size of the resected specimen and its
      technical feasibility. A recently described method of EMR comprises the
      circumferential mucosal incision with a special type of needle-knife and
      subsequent en-bloc resection following prior injection under the lesions, but
      only a few patients with early Barrett's cancer were treated so far. EMR should
      be considered as the treatment of choice for high-grade intraepithelial neoplasia
      (HGIN) and mucosal adenocarcinoma in Barrett's oesophagus. First mid- and long
      term results of endoscopic therapy show promising results, disease-free survival
      is comparable to oesophagectomy. Studies with larger patient numbers proved the
      efficacy and safety of ER, major complications occur <1%. Photodynamic therapy
      and other ablation therapies, although they are comparably effective, have a
      decisive disadvantage in comparison with ER: they lack the opportunity for
      histological processing of the resected specimen and therefore, provide no
      information regarding the depth of invasion of the individual layers of the
      oesophageal wall, and regarding radicality of the resection. Curative endoscopic
      treatment of early neoplastic lesions in Barrett's oesophagus should only be
      carried out in centers with a high-volume.

PMID- 16997167
TI  - Staging in oesophageal cancer.
AB  - Accurate staging defines groups for stage-specific treatment, minimising
      inappropriate treatment. Application of dedicated staging methods - including 16
      64 multidetector computed tomography (CT), endoscopic ultrasonography with fine
      needle aspiration (EUS-FNA) and positron emission tomography (PET) - results in
      better staging of oesophageal cancer. PET as a metabolic imaging technique that
      is usually applied after (or recently in combination with) CT (PET/CT) improves
      the accuracy of non-invasive staging, especially in locally advanced oesophageal
      cancer patients. Whether EUS-FNA or PET/CT should be performed as a first
      diagnostic step is still a matter of debate. Fluoro-2-deoxyglucose (FDG) PET is
      also promising tool in assessing neoadjuvant treatment response. Application of
      these dedicated staging methods has a learning curve, suggesting a prominent role
      for centralisation.

PMID- 16997168
TI  - New insights in the lymphatic spread of oesophageal cancer and its implications
      for the extent of surgical resection.
AB  - In this review new insights in the dissemination pattern of oesophageal tumours
      and the implications for the (extent of) surgical and endoscopic resection are
      discussed. Moreover, the sentinel node concept in oesophageal cancer is
      reconsidered. Three-years survival after a limited resection for cervical-upper
      thoracic oesophageal cancer was 14-20% after an extended resection. No patients
      with distant metastases were alive after five years. Therefore, curative surgery
      for cervical-upper oesophageal cancer with extended lymph node dissection is
      probably only indicated in patients without distant lymph nodes metastases.
      Involved coeliac nodes can be found in tumours of the whole oesophagus.
      Adenocarcinomas of the gastrooesophageal junction do metastasize predominantly to
      the paracardial and lesser curvature regions. No significant difference was found
      in a randomized trial comparing two-field transthoracic resection with limited
      transhiatal resection for adenocarcinoma of the gastrooesophageal junction.(6)
      Subgroup analysis for patients with a distal oesophageal adenocarcinoma revealed
      a 17% survival benefit after transthoracic resection. In several Japanese studies
      a better five-year survival is claimed after a three-field lymph node dissection
      than after a conventional two-field lymphadenectomy. In a randomized study,
      however, no statistically significant difference was found in the short- and long
      term survival nor in the recurrence rate. If an early lesion is limited to the
      mucosa, endoscopic mucosal resection (EMR) could be considered because of the low
      chance of lymph node metastases. However, the technique of EMR has not yet been
      optimized resulting in high numbers of local cancer recurrences and a high need
      for endoscopic re-resections. Only few studies investigated whether the sentinel
      node concept is applicable to the oesophagus or gastric cardia. In one study in
      patients with oesophageal or cardia cancer, the accuracy was 96% and only two
      false negative sentinel nodes were identified. The sentinel node concept in
      oesophageal cancers might change future operative strategies.

PMID- 16997169
TI  - The prevention and management of perioperative complications.
AB  - The most important issues in perioperative complications of oesophagectomy are
      prevention, early detection and appropriate management. Anastomotic leakage is
      the most frequent technical surgical complication. Prevention comprises avoidance
      of tension or impaired vascularization of the conduit and meticulous suture
      technique. Management includes early diagnosis, conservative treatment or
      endoscopic stenting of contained leakage, and re-operation of non-contained
      insufficiency. All other surgical complications - such as bleeding,
      tracheobronchial lesions or chylothorax - are rare and warrant special
      therapeutic modalities. The main general non-surgical complication is
      postoperative pneumonia, which should be prevented by effective pain control
      (especially peridural catheter) and appropriate techniques of artificial
      respiration. Special attention should be offered to postoperative
      tachyarrhythmias and alcohol withdrawal syndrome. Prevention of complications
      also includes exclusion of patients with high operative risk based on scores and
      specific preoperative treatment of risk factors.

PMID- 16997170
TI  - Minimally invasive techniques for oesophageal cancer surgery.
AB  - Innovative minimally invasive surgical (MIS) techniques have been explored for
      the purpose of oesophagectomy since the early 1990s, including various
      combinations of thoracoscopy, laparoscopy or laparoscopic-assisted methods,
      mediastinoscopy and open thoracotomy and laparotomy. The myriad of surgical
      approaches implies a lack of consensus on which is superior. Like open surgery,
      it is perhaps more important to have a tailored approach for the individual
      patient. MIS oesophagectomy has been shown to be feasible, and at least
      equivalent postoperative morbidity and mortality rates to open surgical resection
      have been demonstrated. Selected series have achieved less blood loss, reduction
      in some postoperative complications, decrease in intensive care and hospital
      stay, and better preservation of pulmonary function. Clear proof of superiority
      over conventional oesophagectomy methods however is not forthcoming since
      comparisons were often made with unmatched patient cohorts, and a well conducted
      randomized controlled trial has not been carried out. It is expected that with
      further improvements in instrumentation and experience, these difficult
      procedures may become more accessible and widely practised.

PMID- 16997171
TI  - Response monitoring of neoadjuvant therapy using CT, EUS, and FDG-PET.
AB  - Neoadjuvant or adjuvant multimodality therapy in oesophageal cancer is introduced
      in an effort to improve prognosis. However, in a substantial fraction of patients
      there is no response to this non-surgical therapy. Non-invasive imaging
      modalities such as computed tomography (CT), endoscopic ultrasound (EUS) and 18F
      2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) have been
      evaluated for assessing patient response to therapy, and these are described in
      this review. Currently, FDG-PET seems to be the best available tool for
      neoadjuvant therapy response assessment in oesophageal cancer.

PMID- 16997172
TI  - New developments in palliative therapy.
AB  - Over the past 5 years, new developments in the palliative treatment of incurable
      cancer of the oesophagus and gastro-oesophageal junction have been introduced
      with the aim of palliating dysphagia and improving the survival of patients.
      Stent placement is currently the most widely used treatment for palliation of
      dysphagia from oesophageal cancer. A stent offers rapid relief of dysphagia;
      however, current recurrent dysphagia rates vary between 30 and 40%. Recently
      introduced new stent designs are likely to reduce recurrent dysphagia by
      decreasing stent migration and non-tumoral tissue overgrowth. Intraluminal
      radiotherapy (brachytherapy) has been demonstrated to compare favourably with
      stent placement in long-term effectiveness and safety. A disadvantage of
      brachytherapy, however, is that one-fifth of patients need an additional
      treatment because of persistent tumour growth in the oesophagus. A solution may
      be to administer brachytherapy not in a single fraction but in multiple
      fractions. Finally, efforts have been undertaken to improve survival of patients
      by using chemotherapy. In the future, a multimodal approach--for example by
      combining stent placement with chemotherapy or radiotherapy--may improve the
      prognosis of patients without jeopardizing their quality of life.

PMID- 16997173
TI  - Immune therapy in haematological malignancies.

PMID- 16997174
TI  - The immune system as a foundation for immunologic therapy and hematologic
      malignancies: a historical perspective.
AB  - In this review we aim to provide a historical overview of the immunotherapeutic
      approaches which have been developed for the treatment of hematological
      malignancies. After briefly summarizing the development of the theory of cancer
      immune surveillance, we describe how initial studies discovering the efficacy of
      the immune-mediated graft-versus-tumor effects after allogeneic hematopoietic
      cell transplantation led to new transplantation approaches (termed non
      myeloablative transplantation) relying almost exclusively on graft-versus-tumor
      effects for tumor eradication. We then summarize important steps in the
      development of tumor vaccines and autologous adoptive immunotherapy in patients
      with hematological malignancies. Finally, we describe historical discoveries
      leading to the recent success with monoclonal antibodies as treatment for
      lymphomas, chronic lymphocytic leukemia, and acute myeloid leukemia.

PMID- 16997175
TI  - Radioimmunotherapy for B-cell non-Hodgkin lymphoma.
AB  - Radioimmunotherapy (RIT) combines the targeting advantage of a monoclonal
      antibody with the radiosensitivity of non-Hodgkin lymphoma (NHL) cells. There are
      now two radioimmunoconjugates (RICs) - ibritumomab tiuxetan (Zevalin) and
      tositumomab (Bexxar) - that are approved by the FDA in the US for relapsed low
      grade or follicular B-cell NHL. Both agents target the CD20 antigen on B-cell
      lymphoma cells. In relapsed disease, single doses of RIT produce an 80% overall
      response rate, with approximately 20% of patients achieving durable responses.
      RIT is very well tolerated and is delivered on an outpatient basis over 1 week.
      The only significant toxicity is reversible myelosuppression. Both RIT agents
      have demonstrated high anti-tumor activity in patients who are refractory to
      rituximab. Current trials are testing RIT as initial therapy with rituximab
      maintenance, as adjuvant therapy after chemotherapy, or in high-dose protocols
      with stem-cell support.

PMID- 16997176
TI  - Radioimmunotherapeutic strategies in autologous hematopoietic stem-cell
      transplantation for malignant lymphoma.
AB  - High-dose therapy followed by autologous hematopoietic stem-cell transplantation
      is the preferred therapy for relapsed chemotherapy-sensitive aggressive non
      Hodgkin lymphoma, and may play a role in the treatment of high-risk first
      remission aggressive lymphomas, mantle-cell lymphomas and relapsed follicular
      lymphomas. The primary cause of failure of this approach is disease recurrence
      despite initial responses. Traditional high-dose regimens have relied upon
      myeloablative combinations of chemotherapy with or without total body
      irradiation. In the Western world, over 90% of lymphomas are of B-cell origin,
      and the vast majority of those that come to transplant remain CD20-positive. The
      development of radioimmunotherapeutic approaches targeting this antigen allows
      for either dose escalation with stem-cell support, or the addition of targeted
      therapy to conditioning regimens either as a replacement for total body
      irradiation or in addition to myeloablative chemotherapy regimens. Results to
      date with yttrium-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab
      (Bexxar) suggest that the addition of radioimmunoconjugate therapy to
      conventional conditioning regimens results in a toxicity profile similar to that
      seen with chemotherapy conditioning alone. Demonstration of improved disease
      control will ultimately require phase-III studies, though preliminary results are
      promising.

PMID- 16997177
TI  - BL22 and lymphoid malignancies.
AB  - BL22 is a recombinant immunotoxin containing a truncated form of the bacterial
      toxin Pseudomonas exotoxin A attached to an Fv fragment of an anti-CD22
      monoclonal antibody. Its mechanism of action involves binding to CD22, being
      internalized into the target cell by endocytosis, being processed to generate a
      free toxin fragment which is translocated into the cytoplasm, and finally
      induction of cell death by catalytic inactivation of elongation factor 2. In
      phase-I testing BL22 was very active in chemoresistant hairy-cell leukemia (HCL),
      with 19 (61%) of 31 patients achieving complete remission (CR). The low blood
      counts (cytopenias) which are characteristic of HCL improved in all complete and
      partial responders. Dose-limiting toxicity in HCL was due to a reversible
      hemolytic uremic syndrome (HUS), observed only during cycles 2 or 3. Already
      under way are a phase-II trial in HCL and phase-I trials in chronic lymphocytic
      leukemia (CLL) and acute lymphocytic leukemia (ALL) administering BL22 in a
      modified protocol in an effort to prevent HUS.

PMID- 16997178
TI  - Novel antibody-based therapy for acute lymphoblastic leukaemia.
AB  - In recent decades rapid improvements in the results of treatment of adult acute
      lymphoblastic leukaemia (ALL) have been achieved. This progress has been based
      mainly on intensification and optimization of chemotherapy, risk-adapted use of
      stem-cell transplantation, and improved supportive care. However, results in
      adult patients are still considerably inferior to those in paediatric ALL, and a
      barrier to further intensification of chemotherapy appears to have been reached
      regarding toxicity. More recently, the most significant progress has therefore
      been achieved by individualized and targeted therapy - for example, treatment
      with monoclonal antibodies (MoAbs). ALL blast cells express a variety of specific
      antigens which may serve as targets: e.g. CD19, CD20, CD22, CD33, and CD52. Most
      experience is available for anti-CD20 (rituximab). In ALL, rituximab is combined
      with chemotherapy mainly in mature B-ALL and Burkitt's lymphoma, and interim
      results are very promising. Recently studies with rituximab have also been
      initiated in B-precursor ALL. Other antibodies would be of interest due to a high
      rate of antigen (e.g. CD19) expression in ALL, but these are not yet generally
      available. Clinical application in smaller studies or case reports was reported
      for anti-CD52 and anti-CD33. Overall it can be stated that MoAb therapy in ALL is
      a promising treatment approach. Monotherapy with MoAbs in relapsed ALL has also
      occasionally achieved responses, but greater effects can be expected from
      combination with chemotherapy and treatment in the state of minimal residual
      disease. Details of these regimens - required level of antigen expression,
      timing, schedule, dosage and stage of disease - remain to be defined.

PMID- 16997179
TI  - Monoclonal antibodies and immunoconjugates in acute myeloid leukemia.
AB  - The use of monoclonal antibodies for patients with acute myeloid leukemia is
      based on targeting cell-surface antigens preferentially expressed on leukemic
      blasts while sparing normal cells and tissues. The majority of studies performed
      to date have used antibodies reactive with the CD33 antigen. Phase II studies
      have demonstrated antileukemic responses with all agents, although less so with
      unlabeled antibodies. The most promising results have been obtained in the
      treatment of minimal residual disease in patients with acute promyelocytc
      leukemia. Antibody-targeted chemotherapy with gemtuzumab ozogamicin has also
      shown significant activity in patients with relapsed acute myeloid leukemia.
      Radioimmunotherapy with beta-particle emitters may be most effective for the
      treatment of bulky disease or as part of a conditioning regimen for hematopoietic
      stem-cell transplantation, whereas radioimmunotherapy with alpha-particle
      emitters may be better suited to the treatment of small-volume or minimal
      residual leukemia. Whether or not monoclonal antibody therapy will improve
      disease outcome compared with conventional treatment regimens remains to be
      demonstrated by well-designed clinical trials.

PMID- 16997180
TI  - Donor leukocyte infusions in myeloid malignancies: new strategies.
AB  - Donor leukocyte infusion (DLI) provides direct and potent graft-versus-leukemia
      (GVL) activity to treat relapse after allogeneic stem-cell transplantation. DLI
      is dramatically effective for relapsed chronic myelogenous leukemia (CML), but
      has been less effective for relapse of other myeloid malignancies. Nevertheless,
      most recipients of DLI for relapsed CML, and many patients with relapsed acute
      myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), will experience
      prolonged remissions and probable cure. Graft-versus-host disease remains the
      major complication of DLI. New strategies for GVL induction explore novel dosing
      regimens and both methods of enhancing GVL activity of donor T cells and of
      minimizing toxicity from graft-versus-host disease. Ultimately, the
      identification of the effector cells and target antigens for GVL induction will
      lead to the use of tumor-specific adoptive immunotherapy to both prevent and
      treat relapse with minimal toxicity. Although many issues remain unsettled, the
      potential to harness the graft-versus-leukemia activity of allogeneic donor cells
      provides a powerful new paradigm for the immunotherapy of cancer.

PMID- 16997181
TI  - Immunomodulation in myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) - bone-marrow stem-cell malignancies that
      share pathogenetic overlap with acute myeloid leukemia - are characterized by
      peripheral-blood cytopenias and, in more advanced subtypes, varied degrees of
      maturation arrest. Premature apoptosis of bone-marrow cellular elements
      contributes to ineffective hematopoiesis, which is exacerbated by stromal
      production of inflammatory cytokines. Abrogation of the effects of these
      cytokines represents an area of active clinical research, particularly in the
      treatment of low-risk MDS. Agents such as thalidomide, lenalidomide, and
      infliximab have shown promising efficacy and tolerability in clinical trials, and
      may represent a springboard for future treatment combinations.

PMID- 16997182
TI  - Thalidomide and lenalidomide in multiple myeloma.
AB  - Multiple myeloma is a treatable but not necessarily a curable plasma-cell cancer.
      After decades of minimal progress, two new classes of drugs with novel mechanisms
      of action - immunomodulatory drugs (thalidomide and lenalidomide) and proteasome
      inhibitors (bortezomib) - have been introduced for the treatment of this disease.
      Thalidomide and lenalidomide have shown great activity as single agents and in
      combination with glucocorticoids for the treatment of chemotherapy-refractory
      myeloma. Thalidomide - and more recently lenalidomide - in combination with
      dexamethasone have shown promising results as induction therapy. These drugs can
      easily be combined with other chemotherapeutic agents to potentiate the anti
      myeloma effect. The immunomodulatory function of these drugs can be successfully
      exploited to control residual disease during remission. Thus, both thalidomide
      and lenalidomide have ushered in a new era of optimism in the management of this
      incurable cancer.

PMID- 16997183
TI  - Monoclonal antibody combinations in CLL: evolving strategies.
AB  - Monoclonal antibodies have led to a profound shift in the therapeutic landscape
      of chronic lymphocytic leukemia (CLL). Alemtuzumab and rituximab remain the most
      active antibodies, and their single-agent activity has been established in
      previously untreated and relapsed patients with CLL. Higher response rates and a
      better quality of response through eradication of minimal residual disease have
      been reported with monoclonal antibody combinations. Chemoimmunotherapy regimens
      are being actively explored in frontline CLL therapy, and numerous combination
      regimens have been investigated in relapse. New and more effective therapies are
      shifting the focus from palliation to treatment algorithms with curative attempt.
      Challenges for monoclonal antibody combinations in the future include: (1)
      defining appropriate patient populations for combination therapies; (2) assessing
      the impact of pretreatment biologic prognostic factors; (3) enhancing eradication
      of minimal residual disease; and (4) reassessing response criteria in CLL.

PMID- 16997184
TI  - Alemtuzumab in T-cell lymphoproliferative disorders.
AB  - The humanized monoclonal antibody alemtuzumab binds to the CD52 antigen, a
      glycoprotein which is widely expressed on normal and malignant B and T
      lymphocytes. Recently it has been demonstrated in a number of clinical trials
      that alemtuzumab has clinical activity in mature T-cell diseases such as T
      prolymphocytic leukaemia and cutaneous T-cell lymphoma, inducing responses in up
      to two thirds of heavily pre-treated relapsed/refractory patients. Response was
      associated with improved survival. The toxicity profile for the antibody is
      manageable. The major complications are infusional reactions associated with
      initial injections, and prolonged lymphopenia associated with reactivation of
      viruses. Future studies will be directed towards alternative (subcutaneous)
      routes and schedules of administration, use as first-line therapy, combination
      strategies, and role of alemtuzumab to purge minimal residual bone-marrow disease
      prior to stem-cell transplantation.

PMID- 16997185
TI  - Natural-killer-cell-based treatment in haematopoietic stem-cell transplantation.
AB  - Adoptive immunotherapy using natural killer (NK) cells is currently under
      investigation, especially in situations where anti-neoplastic effect is needed
      but infusion of T cells is considered hazardous, such as in recipients of
      haematopoietic stem-cell transplantation (HSCT) from haploidentical donors. NK
      cell therapy is mainly but not exclusively investigated in the setting of
      allogeneic stem-cell transplantation. NK cells may induce potent anti-leukaemic
      and possibly anti-rejection activity, and may even mitigate graft-versus-host
      disease (GvHD). It remains to be determined whether such effects are clinically
      important and whether or not they are mediated mainly or exclusively by KIR-HLA
      class I interactions. Recent advances in graft engineering has provided methods
      for isolating large numbers of purified NK cells. Several groups have shown that
      clinical-grade NK cells at doses up to 10(7)/kg may be collected and purified for
      the purpose of infusion to patients. Early results in a limited number of
      patients show that these cell doses may be administered without adverse events
      and possibly without inducing GvHD. Further study is required to determine
      whether such infusions will be useful in preventing graft rejection, exerting
      graft-versus-leukaemia effects, and/or hastening immune recovery.

PMID- 16997186
TI  - Reduced intensity conditioning (RIC) haematopoietic cell transplants in elderly
      patients with AML.
AB  - Reduced intensity conditioning (RIC) transplants were first developed almost a
      decade ago to reduce the transplant-related mortality (TRM) of allogeneic
      haematopoietic cell transplantation (HCT) and to make the graft-versus-leukaemia
      effect accessible to patients otherwise ineligible for HCT. Acute myelogenous
      leukaemia (AML) in elderly patients is now a frequent indication for RIC-HCT. The
      major reasons for these rapid developments have been on the one hand the high
      median age of patients with AML coupled with the unsatisfactory results with
      conventional chemotherapy, and on the other hand with the promising results
      already reported for RIC-HCT. Using RIC-HCT, overall survival rates at 2 years of
      45-50% have been observed in patients with AML. This compares favourably with
      overall survival rates of 10-15% under chemotherapy in AML CR1, or no long-term
      survivors in patients >CR2. From the available data we conclude that RIC-HCT is a
      promising treatment for elderly patients with AML. However, phase-III studies
      with unrelated donors will have to be done in order to formally prove its
      superiority in comparison to conventional chemotherapy.

PMID- 16997187
TI  - Immune-cell treatment of Epstein--Barr-virus-associated lymphoproliferative
      disorders.
AB  - Lymphoproliferative disorders associated with Epstein--Barr virus (EBV) after
      bone-marrow or organ transplantation express all the immunogenic EBV antigens,
      and reduction in immunosuppressive treatment can result in permanent resolution.
      As such, the disease lends itself to EBV-directed immune-cell therapy. Successes
      have been achieved with both manipulated and unmanipulated T-cell infusions for
      lymphoproliferations occurring after bone-marrow transplantation. Several
      practical challenges have been overcome in applying EBV-specific T-cell therapy
      to the setting of organ-transplant-related lymphoproliferations. These include
      the generation of autologous cytotoxic T lymphocytes (CTLs), the creation of a
      partially HLA-matched cryopreserved allogeneic CTL bank, and the generation of
      autologous EBV-specific CTLs from EBV-naive pediatric patients. The efficacy of
      immune-cell therapy in the setting of solid-organ transplantation is less well
      established than it is after T-cell-depleted allogeneic bone-marrow
      transplantation, and it is as yet not clear how to best to integrate CTL therapy
      with the anti-B-cell antibody rituximab, which has significant activity against
      these lymphoproliferations.

PMID- 16997188
TI  - Concentration dependence of equivalent conductivity of polyelectrolyte.
AB  - Equivalent conductivity of aqueous solutions of alternating copolymer of iso
      butyl vinyl ether and maleic acid, [poly(iso BVE-co-MA)] was studied, especially
      its polymer-concentration dependence. Various species of counterions such as
      quaternary ammoniumions (NMe4+, NEt4+, NPr4+, NBu4+) and divalent ions (Ca2+,
      Sr2+, Ba2+) were employed besides alkali metal ions. The applicability of
      Manning's conductivity theory was examined for the case of univalent counterions
      at various degrees of neutralization (beta). A major discrepancy against the
      theory was observed at beta = 1.0, while a comparatively good agreement was found
      at beta around 0.5. This suggests that the rod-like polyion model, which is the
      basis of the theory, is applicable near beta = 0.5, where polyions are most
      expanded. The low conductivities in the case of quaternary ammonium counterions
      suggested the ion-binding due to hydrophobic interaction with alkyl side chains.
      Molecular weight dependence was not appreciably observed near beta = 0.5
      similarly to usual polyelectrolytes, but it appeared slightly at beta = 1.0.

PMID- 16997189
TI  - Determination of polymer size distribution by combination of quasielastic light
      scattering and band transport: evaluation of the effect of diffusion.
AB  - In this paper we report a computer simulation study of the effect of diffusion on
      the size distribution obtained by combining light scattering with isokinetic band
      sedimentation or electrophoresis. We find that, under typical experimental
      conditions, the method yields reasonably accurate size distributions for samples
      of particles greater than 10 nm radius. However, caution should be exercised in
      interpreting the results for smaller particles, for which the distortion due to
      diffusion can be considerable.

PMID- 16997190
TI  - An infrared study of carbon monoxide complexes of hemocyanins. Evidence for the
      structure of the co-binding site from vibrational analysis.
AB  - A vibrational analysis was carried out showing that the infrared experimental
      data of 13C and 18O carbon monoxide complexes of hemocyanin of Fager and Alben
      (Biochemistry 11 (1972) 4786) are consistent with a coordination of the carbon
      atom of CO to one of the two copper ions in the active site. This conclusion
      contradicts the original interpretation of Fager and Alben in which oxygen
      coordination to copper was suggested. This vibrational analysis can also be
      applied to the study of Alben and Caughey (Biochemistry 7 (1968) 175) with 13C
      and 18O carbonyl hemoglobin, in which oxygen-coordination to iron was suggested.
      Carbonyl hemocyanins from several sources have also been studied by infrared
      spectroscopy. The single stretching vibration of CO bound to arthropodal (Cancer
      magister) hernocyanin (nu(co)) is at 2042.5 cm(-1), while nu(CO) for gastropod
      (Helix pomatia of the phylum Mollusca) alpha and beta hemocyanin is at 2064.5 cm(
      1)and 2062.5 cm(-1), respectively. The intensities of the CO stretching bands
      were all around 1.5 X 10(4) M(-1) cm(-2). Calculations show that with the present
      attainable accuracy it is impossible to detect hydrogen bonding of exchangeable
      protons to small molecules bound to proteins (for example CO), by comparing its
      stretching frequencies in H2O and D2O buffers.

PMID- 16997191
TI  - Divalent paramagnetic counterions site binding in polyelectrolyte solutions.
      Analysis of the frequency dependence of the water protons magnetic relaxation and
      the characteristic parameters of "site binding".
AB  - Chemical shift and relaxation time measurements on the water protons in
      polyelectrolyte solutions containing divalent paramagnetic counterions have shown
      the existence of three types of counterions: - site bound with loss of water
      molecules and partial or complete release of the electrostriction in the first
      hydration sphere, - atmospherically trapped with no change in hydration, - free.
      The overall stoichiometry of the two former is in agreement with Manning's
      fraction of condensed counterions. A complete analysis of the frequency dependent
      contribution of site bound counterions to the water protons relaxation times
      leads us to interesting conclusions on the modifications of the first hydration
      shell and on the life time of site binding.

PMID- 16997192
TI  - Kinetic studies on the helix-coil transition of fluorescent labeled poly(-L
      lysine) by the temperature-jump technique.
AB  - Fluorescent dansyl labels were covalently attached to poly (L-lysine) (poly(Lys))
      with a degree of polymerization of 300 to 600. The degree of labeling was 0.01 to
      0.085 (mol label to mol amino acid residues). From the decay of the anisotropy of
      fluorescence it was concluded that the labels were highly mobile both in the
      coiled and helical state. A decrease of fluorescence intensity accompanied the
      helix-coil transition. Identical pH induced transition curves were measured by
      circular dichroism and fluorescence. The midpoint of the transition was at pH
      10.2. The kinetics of the transition were studied by temperature-jump relaxation
      using fluorescence detection. A single relaxation phase was observed. The
      relaxation time tau exhibited a distorted bell shaped dependence on the degree of
      helicity f with a maximum value tau(max) = 15 micros at f = 0.3 and 20 degrees C.
      It was independent of polymer concentration and of the degree of labeling. A rate
      constant of helix propagation kF = 10(7) s(-1) was calculated from tau(max) and
      published values of the nucleation parameter sigma. The activation energy was 16
      kJ mol . The observed rate constant is comparable to that of poly(L-glutamic
      acid) but two orders of magnitude smaller than that found for polyamino acids
      with nonionizable side chains.

PMID- 16997193
TI  - The frequency distribution of the orientation factor of dipole-dipole
      interaction.
AB  - An analytical expression is derived for the frequency distribution of the
      orientation factor in the non-radiative transfer of electronic excitation energy.

PMID- 16997194
TI  - Coexistence, competition and hypercyclic interaction in some systems of
      biological interest.
AB  - Systems of differential equations which describe the selective behavior of self
      replicating macromolecules or species under the constraint of constant
      organization are classified according to their coexistent and competitive
      behavior as well as the cooperative and/or hypercyclic nature of the inter
      species interactions. Two theorems are proved which relate the possibilities for
      coexistence and competition among species to the presence or absence of
      hypercyclic linkages.

PMID- 16997195
TI  - The alkaline transition of swine pepsinogen.
AB  - At alkaline pH, swine pepsinogen is reversibly inactivated in a transition which
      involves the cooperative release of two protons from the molecule and is governed
      by a pK = 9. Stopped flow kinetic studies on the absorbance changes accompanying
      this reaction show that it can be resolved into two steps, with increasing pH; a
      slow conformational change, whose amplitude follows the ionisation curve of one
      group of pK = 9.9, followed by a rapid pH dependent conformational change, linked
      to a group of pK = 8.2. The pH dependence of the rate of the slow step is
      interpreted to show the presence of a protonated group which cannot ionise in the
      neutral form of the zymogen, but is in slow equilibrium with a form where it
      titrates with a pK = 6.8. At the same time, a histidine in the amino terminal
      region of the protein becomes reactive to diethyl pyrocarbonate, suggesting this
      to be the group which triggers the reaction.

PMID- 16997196
TI  - Interaction of nucleic acids with electrically charged surfaces. VI. A
      comparative study on the electrochemical behaviour of native and denatured DNAs
      at graphite electrodes.
AB  - Adsorption and electrochemical oxidation of deoxyribonucleic acid (DNA) at a
      pyrolytic graphite electrode (PGE) and a paraffin wax-impregnated spectroscopic
      graphite electrode (WISGE) were studied using differential pulse voltammetry. DNA
      is adsorbed at the surface of the graphite electrodes in a broad range of
      potentials including the potentials of electrochemical oxidation of DNA. Both
      native and denatured DNAs yield two single, well-defined and separated peaks, G
      and A, on the differential pulse voltammograms at the PGE and WISGE. The more
      negative peak, G, corresponds to electrochemical oxidation of guanine residues,
      whereas the more positive peak, A, corresponds to electrochemical oxidation of
      adenine residues. Peaks G and A of native DNA occur at the same potentials as
      peaks G and A of denatured DNA. However, electrochemical oxidation of adenine and
      guanine residues at graphite electrodes is markedly suppressed in native DNA. The
      heights of the peaks G and A represent a sensitive indicator of the helix-coil
      transition of DNA. An analysis of the product of interaction of a sample of
      native DNA with a large pyrolytic graphite electrode in the presence of
      formaldehyde at approximately neutral pH did not prove changes in the secondary
      structure of native DNA due to its interaction with the graphite electrode. It is
      suggested that the decreased differential pulse-voltammetric activity of native
      DNA is connected with its decreased flexibility.

PMID- 16997197
TI  - Scanning molecular sieve chromatography of interacting protein systems. II.
      Determination of large zone transport parameters by the difference profile method
      at low solute concentration.
AB  - The experimental determination of difference profiles for the study of large zone
      transport processes by scanning molecular sieve chromatography is described.
      Using the difference profile method, the progesterone-induced purple glycoprotein
      of the porcine uterus was found to exist as monomeric units in high ionic
      environment, with a partition coefficient of 0.269, partition cross-section of
      0.488, partition radius of 25 A and a molecular weight of 33500 g mole . The
      technique was further applied in examining the association-dissociation
      properties of oxyhemoglobin. In a high tonic environment, the partition
      coefficient was found to be 0.365 for dimer and the partition cross-section,
      0.419; for the tetramer in low ionic strength solution, the partition coefficient
      was 0.275 and the partition cross-section 0.377, with a dissociation constant of
      1.03 x 10(-6) mole/1. This new technique should prove applicable in (1) readily
      locating the centroid positions of transport boundary profiles at the lowest
      practicable protein concentration limits, (2) demonstrating the characteristic
      boundary shape and concentration-dependent centroid position for an interacting
      solute, (3) determining the axial dispersion coefficient characteristic of solute
      turbulence within the gel matrix, and (4) distinguishing the boundary between low
      and high ionic strength solvent phases in the gel column.

PMID- 16997198
TI  - Scanning molecular sieve chromatography of interacting protein systems. III.
      Effect of kinetic parameters on the large zone boundary profiles for local
      equilibration between mobile and stationary phases.
AB  - Large zone reaction boundary profiles for molecular sieve chromatography as
      affected by kinetic parameters have been simulated for local equilibration
      between the mobile and stationary phases. Our studies of monomer-dimer and
      monomer-tetramer systems indicate that in a slowly equilibrating system, the
      kinetic controls operating between the mobile and stationary phases contribute
      most significantly to the overall boundary profile. In a rapidly equilibrating
      system, however, the kinetic parameters k(ij) and k(ji) operating in the mobile
      phase are the principal determinants of the reaction boundary, while the kinetic
      effects of k(ii) and k-(ii) between the mobile and stationary phases are minimal.

PMID- 16997199
TI  - Scanning molecular sieve chromatography of interacting protein systems. IV. The
      difference profile method as applied to the Gibbs-Duhem expression in the
      analysis of the dimer-tetramer equilibria of oxyhemoglobin A.
AB  - The recently-developed large zone difference profile method in scanning molecular
      sieve chromatography is applied to the analysis of the Gibbs-Duhem expression in
      the tetramer-dimer equilibrium of human oxyhemoglobin A. The preferential binding
      term and solvation parameters of the Hofmeister anion phosphate are examined.
      Results indicate that as the concentration of phosphate ions increase, a hydrated
      phosphate is formed which enhances the association by perturbing the solvation
      layer of the hemoglobin molecules. The standard free energy change at a given
      Hofmeister anion activity of InA(x) = -3.2476 is 9.4 +/- 0.2 kcal mole . DeltaG
      degrees at InA(x) = -1.2711 is 10.90 +/- 0.05 kcal mole , suggesting that
      approximately 11 kcal are required to dissociate one mole of tetramer into dimer.

PMID- 16997200
TI  - A rotational diffusion coefficient of the 70S ribosome determined by depolarized
      laser light scattering.
AB  - We have obtained a rotational diffusion coefficient of the 70S ribosome isolated
      from Escherichia-coli (MRE-600), from the depolarized light scattering spectrum
      measured by photon correlation spectroscopy. The intensity correlation function
      of depolarized scattered light contains contributions due to multiple scattered
      and anisotropy scattered light from the ribosomal particle. We discuss
      extensively the subtraction procedure used to obtain the rotational correlation
      time from the experimental correlation function. We have also obtained the
      translational diffusion coefficient from the same sample by determining the
      polarized correlation function. The hydrodynamic radius determined from the
      rotational diffusion coefficient is only slightly larger than the radius obtained
      from the translational diffusion coefficient. Therefore the ribosomal particle
      has a non-spherical shape. This conclusion, however, could be impaired by the
      effect of free draining of the ribosome.

PMID- 16997201
TI  - Interfacial behavior of uracil derivatives.
AB  - The adsorption of a number of methylated uracil derivatives and of 5-fluorouracil
      has been studied by surface electrochemical methods at a mercury electrode. All
      derivatives exhibit an initial or dilute adsorption region where they are
      adsorbed flat on the electrode surface and are bound by pi-electron overlap with
      the electrode. Uracil, thymine, 1,5-dimethyl-uracil, 5,6-dimethyluracil, 1,5,6
      trimethyluracil and 5-fluorouracil undergo a surface reorientation from the
      initial flat solution activities for each compound. An unsubstituted N(3)-H group
      is an absolute requirement for a uracil derivative to be capable of adopting the
      perpendicular surface stance. In the perpendicular orientation the uracil
      derivative appears to be bound to the electrode primarily via a N(3)-H--(-)
      electrode bond although a similar but weaker hydrogen bond can be formed via the
      N(1)-H group for certain compounds.

PMID- 16997203
TI  - Rotor speed dependent sedimentation of circular and linear DNA.
AB  - The sedimentation rate of large, linear DNA molecules has been shown to be rotor
      speed dependent (Rubenstein and Leighton, Biophys. Chem. 1 (1974)). In this
      communication we report the first studies designed to measure the rotor speed
      effect with a homogenous, linear viral DNA larger than bacteriophage T2 DNA. We
      also report the first studies using a homogenous, circular episomal DNA of known
      molecular weight. For this circular DNA a small rotor speed effect, previously
      unsuspected, was discovered.

PMID- 16997202
TI  - Influence of chlorophyll a on intermolecular interactions in liquid crystal.
AB  - Studies of the variability of the spectral properties (linear dichroism,
      polarized fluorescence and the energetic separation of the absorption and
      emission bands) of chlorophyll a in a nematic liquid crystal matrix with respect
      to the effects of solute concentration and the external electric fields were
      made. A close examination of the above mentioned types of variability suggest
      that the pigment molecules can influence a high initial order of the liquid
      crystal matrix. These structural changes of the matrix can be explained by the
      assumption that two types of chlorophyll with different orientations occur: the
      surface layers with the high degree of orientation, and a central volume of the
      sample with disordered molecules. The ordered molecules are sensitive to an
      reorientation by the external electric field.

PMID- 16997204
TI  - On the effect of temperature on the ultraviolet spectra of protein chromophores.
AB  - The thermal perturbation difference spectra - TPDS (15-30 degrees C) - of N
      acetyl-tyrosine-ethyl ester and o-methyl-N-acetyl-tyrosine were studied in ethyl
      acetate and dimethyl ether with/without the addition of butanol which served as a
      proton donor in hydrogen bonding. In all cases the longwave shift of the
      absorption spectrum is shown to be a principal factor that determines the origin
      of TPDS and the hydrogen bonding has no effect on these spectra. These results
      contradict the view that the red shift of protein chromophore spectra at the
      elevation of temperature is a unique feature of water as a solvent. The water
      inaccessible chromophores in proteins may be perturbed by temperature increase,
      producing red shift.

PMID- 16997205
TI  - Examination of the limiting laws of polyelectrolytes and counterion condensation
      II.
AB  - The two phase model of polyelectrolyte solutions, which has been developed
      recently, is examined in a further detail. The binding free energy, which was
      introduced in the previous paper (J. Chem. Phys. 81 (1977) 1929), is replaced by
      the entropy of the condensed phase. This replacement leads to a detailed picture
      of the condensed phase. In a mixed system of mono- and divalent counterions, a
      couple of possibilities are examined in interpreting the condensation volume,
      which corresponds to the condensation entropy.

PMID- 16997207
TI  - The one-dimensional diffusion coefficient of proteins absorbed on DNA
      hydrodynamic considerations.

PMID- 16997206
TI  - Relaxation kinetics of E coli ribosomes: evidence for the reaction of 30S . IF3
      complex with 50S ribosomal subunits.
AB  - Addition of initiation factor IF3 to solutions of E.coli ribosomes dramatically
      alters their behavior in pressure-jump relaxation kinetic experiments in which 90
      degrees light-scattering is used to monitor the macromolecular reaction. The
      effect of IF3 on relaxation processes attributed to "tight" couples is strongly
      dependent on the Mg2+ concentration. At 2.5 mM Mg2+, addition of 1 molar
      equivalent of IF3 decreases the relaxation amplitude by a factor of 3 relative to
      ribosome solutions without IF3. However, at 5.0 mM Mg2+, addition of 1 molar
      equivalent of IF3 produces a marked increase in the relaxation amplitude, by a
      factor of 2-8 fold relative to ribosomes in the absence of IF3. IF3 has no effect
      on the relaxation process attributed to "loose" couples at 10 mM Mg2+. While we
      are unable to propose a precise mechanism for IF3 action with the data on hand,
      our results require that the 30S . IF3 complex either reacts with the 50S
      subunit, forming a 70S . IF3 intermediate, or acts as a pool of reactive 30S
      subunit. Further kinetic evidence is required to distinguish between these
      possible pathways.

PMID- 16997208
TI  - Polarized fluorescence in an electric field: steady state and transient values
      for the fourth moment of the orientation function at arbitrary fields.
AB  - Steady state and time dependent expressions for the field dependence of the
      fourth moment of the orientation function at arbitrary fields, which are
      requested for the interpretation of polarisation of fluorescence in an electric
      field, have been obtained for permanent and induced dipole orientation. Some
      general features of the results and some problems connected with their
      application are pointed out.

PMID- 16997210
TI  - Brownian motion of helical flagella.
AB  - We develops a theory of the Brownian motion of a rigid helical object such as
      bacterial flagella. The statistical properties of the random forces acting on the
      helical object are discussed and the coefficients of the correlations of the
      random forces are determined. The averages <z(2)(t)>, <theta(2)(t)> and
      <z(t)theta(t)> are also calculated where z and theta are the position along and
      angle around the helix axis respectively. Although the theory is limited to short
      time interval, direct comparison with experiment is possible by using the
      recently developed cinematography technique.

PMID- 16997209
TI  - Gel matrices for scanning gel chromatography.
AB  - I have examined the light-scattering behavior of a number of gel matrices used in
      gel filtration chromatography. The angular dependence of light scattering by
      Sephadexes is consistent with treatment of the particles as large scattering
      particles with a low refractive index increment (mu). Such particles scatter
      light almost exclusively in the forward direction, permitting their use in direct
      scanning gel chromatography systems without corrections for multiple scattering
      and the consequent variation in pathlength through the column. Any matrix
      material with an appropriate combination of these two properties (large effective
      size and low mu relative to solvent) will perform reasonably well in direct
      scanning systems while any material with very small effective particle size
      (agaroses) or high mu (glass beads) may be expected to perform poorly. Agaroses
      may be acceptable for work in the visible region of the spectrum while glass
      beads are not.

PMID- 16997211
TI  - Analysis of fluorescence anisotropy decays by a least square method.
AB  - A method of fluorescence anisotropy decay analysis is described in this work. The
      transient anisotropy r(ex)(t) measured in a photocounting pulsefluorimeter is
      fitted by a non linear least square procedure to the ratio of convolutions of the
      apparatus response function g(t) by sums of appropriate exponential functions.
      This method takes rigorously into account the apparatus response function and is
      applicable to any shape of the later as well as to any values of fluorescence
      decay times and correlation times. The performances of the method have been
      tested with data simulated from measured response functions corresponding to an
      air lamp and a high pressure nitrogen lamp. The statistical standard errors of
      the anisotropy deca parameters have been found to be smaller than the standard
      errors previously calculated for the moment method. A systematic error delta in
      the fluorescence decay time entailed an error deltatheta in the correlation time
      such as Deltatheta/theta < deltatau/tau. By this method, good fitting of
      experimental data have been achieved very conveniently and accurately.

PMID- 16997212
TI  - Kinetics of reversible protein denaturation. A study on aplysia myoglobin.
AB  - The kinetics of denaturation and renaturation of Aplysia Myoglobin by temperature
      jump and stopped-flow are reported. The time course of the unfolding and
      refolding reveals the presence of significant amounts of intermediates both in
      absence and in the presence of alcohols. A linear three states reaction mechanism
      is proposed and discussed.

PMID- 16997213
TI  - Linear cooperative binding of large ligands involving mutual exclusion of
      different binding modes.
AB  - A rigorous treatment is given for mutually exclusive multiple mode cooperative
      binding on a linear structure of equivalent binding "contacts". This will be of
      special interest with regard to larger ligands implicating the possibility that
      there are different kinds of binding interactions with more than one monomeric
      sub unit of a linear biopolymer. Quantitative evaluation of binding properties is
      shown to be essentially based on calculating the largest root of an algebraic
      equation. The whole procedure can be practically executed by means of a fairly
      simple computer program. Various typical examples comprising only two modes are
      discussed in more detail. For some nucleotide-polylysine systems definite binding
      parameters have been determined from pertinent experimental data.

PMID- 16997214
TI  - Molecular weights from approach-to-sedimentation equilibrium data using nonlinear
      regression analysis.
AB  - Data obtained from early times during the transient period of sedimentation
      equilibrium experiments are analyzed using an approximate solution to the Lamm
      equation to estimate s/D. The Cr versus r data obtained at several times during
      approach-to-equilibrium are analyzed using a nonlinear least squares algorithm
      and Fujita's approximate solution. This procedure was tested using D-Ser13
      somatostatin, ribonuclease, and ovalbumin. The results obtained demonstrate that
      for monodisperse samples s/D may be rapidly and reliably estimated using this
      method.

PMID- 16997215
TI  - An approximate solution to the Lamm equation.
AB  - An approximate solution to the Lamm equation subject to the initial and boundary
      conditions for conventional sedimentation velocity experiments is derived and
      compared with the approximate solution of Fujita and MacCosham. Calculations with
      this solution demonstrate that the half-height method of estimating sedimentation
      coefficients yields correct values for epsilon < 0.02.

PMID- 16997216
TI  - Isoelectric focusing of interacting systems. IV. interaction of macromolecules
      with each other and with ligands.
AB  - The theoretical isoelectric focusing behavior for rapidly reversible, bimolecular
      complexing between two macromolecules depends upon the relative value of the
      isoelectric point of the complex. When it is intermediate in value, the transient
      patterns exhibit three peaks. As equilibrium is approached the central peak of
      complex disappears leaving two reactant peaks. When the isoelectric point is
      acidic or alkaline to both reactants, the equilibrium pattern also shows two
      peaks; but in this case only one is pure reactant, the other being a reaction
      zone. The two cases can be distinguished by varying the relative amounts of
      reactants. Transient patterns for ligand-binding exhibit a peak of unliganded
      protein and a reaction zone. As the charged ligand is driven out of the focusing
      column the reaction zone disappears, so that the equilibrium pattern shows only a
      peak of unliganded protein. In general, the isoelectric point of the complex
      cannot be determined from the transient patterns.

PMID- 16997217
TI  - Isoelectric focusing of interacting systems. V. Determination of ligand-binding
      constants.
AB  - A theory is formulated for an isoelectric focusing procedure which permits
      determination of intrinsic ligand-binding constants. The protein is first focused
      in the absence of ligand, after which ligand is added to the appropriate
      electrode compartment and then driven by the electric field into the focusing
      column where it complexes with the protein. The band of protein and its complexes
      moves to the constituent isoelectric point. An equation linearly relates the
      reciprocal of the overall distance moved to the reciprocal of the local
      concentration of ligand. The quotient of the intercept and slope gives the
      intrinsic binding constant. If the concentration of ligand in the electrode
      compartment is used in lieu of the local concentration, an apparent constant is
      obtained. Extrapolation of the apparent constant to infinite dilution of protein
      gives the intrinsic constant. For certain systems, conditions may be realized
      which give an apparent constant within 4% of the intrinsic constant.

PMID- 16997218
TI  - Fluorescence photobleaching recovery measurement of protein absolute diffusion
      constants.
AB  - The technique of fluorescence photobleaching recovery [Axelrod et al., Biophys.
      J. 16 (1976) 1055] has been applied to the measurement of absolute diffusion
      constants of a number of fluoiescein isothiocyanate-labeled proteins. Measured
      diffusion constants agree to within +/- 7% of published values for the
      underivatized proteins. The method has sufficient sensitivity to reveal the
      concentration dependence at neutral pH of the diffusion constant of alpha
      chymotrypsin. The rapidity with which the labelling and measurements can be
      performed and the small amount of material required suggest the technique may be
      useful in rapid characterization of small protein samples. Some developments in
      optical and electronic systems and in data processing for this technique are
      discussed.

PMID- 16997219
TI  - Demonstration of G . U wobble base pairs by Raman and IR spectroscopy.
AB  - When guanine and uracil form hydrogen bonds in the pairing scheme first proposed
      by Crick one would expect that poly(A,G) will form an unperturbed double helix
      with poly U at room temperature in a dilute electrolyte solution (0.1 M NaCl). We
      have demonstrated by Raman- and IR-spectroscopy that the secondary structure of
      poly(A.G) . poly U is very similar to the structure of poly A . poly U; only the
      thermal stability of the double helix seems slightly lower than the stability of
      poly A . poly U, whereas the average helix length is unaffected by the dispersed
      G . U base pairs. From our input ratio of guanine and adenine we estimate that
      about every fourth base pair is a wobble pair.

PMID- 16997220
TI  - Rates of diffusion controlled reactions in one, two and three dimensions.
AB  - The dimensionality of diffusion may markedly affect the rate and economy of
      diffusion controlled reactions. Moreover, the degree of dependence of the steady
      state rate of these reactions on the concentration of each of the two reacting
      species is also dictated by the dimensionality and it ranges from linear
      dependence in the three dimensional case to a nearly square dependence in the one
      dimensional case. These theoretical observations emerge from a direct analysis of
      the steady state diffusion controlled rates which are derived here using a simple
      straightforward approach. This approach is based on the conjecture that in the
      steady state the rate of diffusional encounters between the two reaction partners
      equals to the sum of the encounter rates of two independent processes which are
      obtained by alternately immobilizing one of the reaction partners while the other
      partner diffuses freely. Unlike Smoluchowski's classical approach, the presented
      point of view permits to obtain in a unified fashion reaction rates for all
      dimensionalities.

PMID- 16997221
TI  - Diffusion-controlled mean reaction times in biological systems with elliptical
      symmetry.
AB  - The mean reaction (encounter or absorption) time is calculated in terms of the
      system size and reaction probability parameters for three-dimensional systems
      with diffusion-controlled dynamics and in which there is spherical, prolate
      spheroidal or oblate spheroidal geometry. Analytical and numerical comparisons
      are made among the three geometries. For completeness, similar results are
      derived for a two-dimensional elliptically symmetrical system, and the
      probability of non-absorption (or reaction) is found for a semi-infinite three
      dimensional space with prolate or oblate spheroidal symmetry.

PMID- 16997222
TI  - Electrostatic interactions at charged lipid membranes. Hydrogen bonds in lipid
      membrane surfaces.
AB  - Hydrogen-bonded structures within lipid membrane surfaces are not disrupted by
      water and are of thermodynamic and therefore potential structural importance in
      biological systems.

PMID- 16997223
TI  - Kinetics of transport of hydrophobic ions through lipid membranes including
      diffusion polarization in the aqueous phase.
AB  - Previous interpretations of the kinetics of transport of hydrophobic ions through
      membranes have been based on one of three limiting assumptions. Either diffusion
      in the aqueous phase was taken to be rapid, or ionic motion was constrained to
      the membrane or a steady state was presumed to be established within the
      membrane. We present a general treatment of the coupled diffusion process through
      both the aqueous phase and the membrane; our theory contains the previous results
      as limiting cases. It is applied to voltage jump-current relaxation experiments
      on black lipid membranes in the presence of dipicrylamine or sodium
      tetraphenylborate. We have attempted to establish the rate of desorption from the
      membrane. For the system phosphatidylserine/tetraphenylborate, the rate of
      desorption and the rate of translocation were found to be comparable.

PMID- 16997224
TI  - The binding of a neutral aromatic molecule to a negatively-charged lipid
      membrane. I. Thermodynamics and mode of binding.
AB  - This paper presents a detailed study of the binding of the fluorescent dye N
      phenyl naphthylamine (NPN) to bilayers composed of the negatively-charged
      phospholipid methylphosphatidic acid. Binding to the liquid-crystalline membrane
      is enthalpy-driven. It is shown by determination of the binding constant and
      confirmed by n.m.r. that most of the dye ("guest") molecules reside between the
      lipid hydrocarbon chains at a fixed distance from the head-group, and are not
      distributed uniformly throughout the hydrocarbon phase. Each guest molecule is
      surrounded by about four lipid molecules. Transition of the membrane from the
      liquid-crystalline to the crystalline state results in almost total expulsion of
      the bound NPN into the water phase. Electrostatic theory is developed to find the
      effect of electrostatics upon the binding of a neutral molecule to charged
      membranes. Although the charge product is zero, electrostatic interactions play a
      part in determining the strength of binding, if each guest molecule incorporated
      increases the area of the membrane. For NPN this increase was found to be ca. 41
      A(2).

PMID- 16997225
TI  - The binding of a neutral aromatic molecule to a negatively-charged lipid
      membrane. II. Kinetics and mechanism.
AB  - The kinetics of the binding of the fluorescence indicator N-phenyl naphthylamine
      to bilayer vesicles of C12-methyl-phosphatidic acid have been investigated by
      means of the temperature-jump relaxation technique utilizing fluorescence light
      detection. Single-exponential relaxation curves were observed, with time
      constants in the range 0.2-3 ms. The concentration dependence of the relaxation
      time yielded an apparent association rate constant (expressed in terms of
      monomeric phospholipid) of k(on) = 5 x 10(6) M(-1) s(-1) in aqueous solution at
      25 degrees . The activation energy and viscosity dependence associated with the
      binding rate show that this process is actually diffusion-controlled. The theory
      of diffusion-controlled reactions then allows a determination of the average size
      of the bilayer vesicles and of the true rate constant for the association of the
      indicator molecules with the vesicles. Assuming spherical geometry for the
      vesicles, the values are: r(ves) = 190 A, which corresponds to 20000 lipid
      molecules per vesicle and k'(on) = 1 x 10(11) M(-1) s(-1) (25 degrees). The
      correctness of this size-determination was confirmed semi-quantitatively by
      electron microscopy. Since in fact a distribution of vesicle sizes must be
      present, a discussion is included of the relaxation function which the system is
      expected to take in the general case. Biological implications of diffusion
      control for the transport of non-polar substances and for lipid mixing are
      indicated.

PMID- 16997226
TI  - Equilibrium and kinetic studies on the interaction of tetracyclines with calcium
      and magnesium.
AB  - The interaction of Ca2+ and Mg2+ with three Tetracycline antibiotics
      (tetracycline, chlorotetracycline, and oxytetracycline) has been investigated.
      Spectrophotometric measurements have been used to determine the apparent
      association constant for this interaction as a function of pH. It is shown that
      the results are consistent with a model in which the metal ion can form complexes
      with both the fully-deprotonated and mono-protonated forms of the Tetracycline.
      The temperature-jump relaxation method has been used to measure the kinetics of
      formation of the complexes of Mg2+ with the Tetracyclines. The results are
      compared with those of previous studies of Mg2+ complex formation reactions and
      it is shown that the data is consistent with the normal dissociative model. A
      possible role for metal ion chelation in the mechanism of antibacterial action of
      the Tetracyclines is discussed.

PMID- 16997227
TI  - Theory for the separation of very large DNA molecules by radial migration.
AB  - The separation of very large biological macromolecules is not presently possible
      with conventional techniques such as sedimentation and gel electrophoresis. For
      molecules larger than about 5 x 10(8) daltons, such as chromosomal DNA, it is
      necessary to develop new separation methods. Herein we describe the principle for
      a new device which shows promise for separating molecules in this size range, as
      a function of molecular weight. It is based on the deformability of random coil
      molecules, and the normal stresses which they generate in a certain class of
      rheological flows. In particular, when a solution of large DNA molecules (we have
      used the intact chromosome from phage T2) is contained between two concentric
      cones, one of which rotates relative to the other, there will be a "radial
      migration" of the DNA toward the center of the cones. The velocity with which the
      macromolecules migrate is highly dependent on the molecular weight, and therefore
      the potential exists for separating these large molecules.

PMID- 16997228
TI  - Electrostatic interactions at charged lipid membranes. Calcium binding.
AB  - A quantitative study of calcium-ion binding by the negatively-charged
      phospholipid methylphosphatidic acid is presented. Experimental results are
      compared with the predictions of the Gouy-Chapman theory, taking into account
      both the ions bound at the membrane surface and the ions held in the diffuse
      layer. This theory suffices to explain the titration of the calcium/lipid system,
      but fails to explain completely the behaviour of the ordered-fluid transition
      temperature, which shows a splitting that according to electrostatic theory alone
      should not occur. The dependence of the calcium-lipid binding constant. upon 1: 1
      electrolyte concentration is correctly predicted by the theory; the latter
      however gives equations which can only be solved numerically. A simple,
      approximate equation is therefore given (in the text, eq. 34) for the prediction
      of the degree of calcium binding to a negatively-charged lipid membrane.

PMID- 16997229
TI  - Motion of the lengthened zwitterionic head groups of C16-lecithin analogues in
      aqueous solutions as studied by dielectric relaxation measurements.
AB  - Phosphatidyl choline analogues with increased phosphate-trimethylammonium
      distance were synthesized and aqueous solutions of these bilayer forming
      phospholipids were prepared. Dielectric spectra of the solutions were measured at
      several temperatures around the crystalline/liquid-crystalline phase transition
      temperature of the samples. The observed data are treated in terms of a Debye
      relaxation function and also of a relaxation function based on a theoretical
      model of the aqueous solutions of multibilayer vesicles. As a noteworthy result,
      a pronounced cooperativity effect in the diffusive motions of the zwitterionic
      head groups emerges. The degree of cooperativity depends on the radius of
      curvature of the multibilayer vesicles and also on the length of the phospholipid
      zwitterions. The values for the mobility of the trimethylammonium group are of
      the same order of magnitude as those for the mobility of whole phospholipid
      molecules in its lateral diffusive motion. Indications for a phase transition at
      a temperature above the main transition temperature are found with solutions of
      C16- lecithin analogues with 9 and 10 methylene groups between the phosphate and
      the trimethylammonium group.

PMID- 16997230
TI  - On thermal transitions in biological macromolecules.
AB  - The thermal transitions shown by macromolecules are to be understood as an
      allosteric phenomenon. They can be dealt with in terms of the same linkage
      principles as those governing the binding of a chemical ligand. This provides a
      basis for analyzing the observed differences between the reversible heat
      denaturation of proteins and the melting of nucleic acids. It also adds to our
      understanding of cooperativity and heterotropic linkage.

PMID- 16997231
TI  - The influence of dioxan on the bilayer and monolayer phase transition of
      phospholipids.
AB  - The influence of 1.4.-dioxan on the bilayer phase transition of various
      phospholipids was studied by differential scanning calorimetry and turbidity
      measurements. The addition of 1.4.-dioxan to lipid bilayers decreases the
      transition temperature T(m) increases the transition enthalpy of the transition.
      The cooperativity of the transition is unaffected. The phospholipid monolayer
      transition from the liquid-condensed to the liquid-expanded phase was measured by
      recording area versus temperature curves at constant surface pressure (isobars).
      The monolayer transition temperature at constant surface pressure is increased
      when 1.4.-dioxan is added to the subphase. The change in molecular area becomes
      larger. A comparison of monolayer isobars on water and water/dioxan as subphase
      at constant surface tension rather than surface pressure leads to a decrease of
      the transition temperature on water/dioxan as subphase. This decrease as well as
      the larger change in molecular area at the monolayer transition can be correlated
      to the decrease in Tm and the increase in the transition enthalpy of the
      corresponding bilayer system. 1.4.-Dioxan seems to accumulate at the lipid head
      group/water interface, thus lowering the tension of the bilayer membrane. This
      cyclic ether can be used for altering the characteristics of bilayer membranes
      without disturbing the lipid chain organization.

PMID- 16997232
TI  - Thermochemistry of aqueous solutions of alkylated nucleic acid bases. I. Apparent
      molar heat capacities of uracil, thymine and their derivatives.
AB  - Apparent molar heat capacities phiC(p(1,3)) of uracil, thymine and a series of
      their alkylated derivatives: m(1)Ura,m(1,3)(2) Ura, m(1,3)(2)Thy,
      mi(1,3,6)(3)Ura, m(1,3)(2),e(5)Ura and e(1,3)(2)Thy in dilute aqueous solutions
      were measured in the temperature range of 293.15-388.15 K, using a differential
      adiabatic scanning microcalorimeter. They were found to lie (i) much higher than
      the estimated heat capacities C(p)(s) of solid compounds, (ii) comparable with
      the respective partial molar heat capacities at infinite dilution, C(o)(p2), and
      (iii) linearly related to the number nH of hydrogen atoms covalenuy bound to the
      solute molecules. The increment thus obtained DeltaC(o)(p2)=42.8 J mole(-1) K(
      1)n(-1)(H) per each hydrogen atom at 298.15 K proved (i) to coincide closely with
      those found previously for homologous series of aliphatic amides and
      hydrocarbons, and (ii) to decrease with a rise of temperature. These findings
      imply the involvement of hydrophobic hydration of the solutes.

PMID- 16997233
TI  - Thermochemistry of aqueous solutions of alkylated nucleic acid bases. II.
      Apparent molar relative enthalpies of dilution of solutions containing uracil and
      thymine derivatives.
AB  - Apparent molar relative enthalpies of dilution phi(L)of aqueous solutions of a
      series of alkylated diketopyrimidines: m(1)Ura, m(1,3)(2)Ura, m(1,3)(2)Thy,
      m(1,3,6)(3)Ura and e(1,3)(2)Thy were measured as a function of concentration of
      the solutes at three temperatures 298.15, 308.15 and 318.15 K. Dilution proved to
      be an endothermic process over the whole range of molalities m and temperatures
      studied for all compounds except the e(1,3)(2)Thy solution, the dilution of
      which, with the exception of the lowest concentrations (m > 0.2-0.3) was an
      exothermic process. Partial molar relative enthalpies of dilution -L(2)(m)
      derived from phi(L)(m) functions were analysed as if they were composed of two
      additive contributions: an endothermic one -L(2), (m(1)) and an exothermic one
      1.2, (m(as)0), owing to the presence in the solutions of a free monomer m(1) or
      associated species m(as), respectively. Partial molar heat capacities of the
      solutes, evaluated by differentiation of -L(2)(m) functions in respect to
      temperature, decreased with the rise of concentration in the order of the
      tendency of the solutes to stacking association. Changes in heat content and in
      heat capacity of solutions upon their dilution are interpreted in terms of
      involvement of hydrophobic hydration and association of the solutes.

PMID- 16997234
TI  - Interaction of nucleic acids with electrically charged surfaces. VII. The effect
      of ionic strength of neutral medium on the conformation of dna adsorbed on the
      mercury electrode.
AB  - Triangular-wave direct current (d.c.) voltammetry at a hanging mercury drop
      electrode and phase-selective alternating current (a.c.) polarography at a
      dropping mercury electrode were used for the investigation of adsorption of
      double-helical (ds) DNA at mercury electrode surfaces from neutral solutions of
      0.05-0.4 M HCOONH4. It was found for the potential region T (from -0.1 V up to
      ca. -1.0 V) that the height of voltammetric peaks of ds DNA is markedly
      influenced by the initial potential only at relatively low ionic strength (mu)
      (from 0.05 up to ca. 0.3). Also a decrease of differential capacity (measured by
      means of a.c. polarography) in the region T depended markedly on the electrode
      potential only at relatively low ionic strength. The following conclusions were
      made concerning the interaction of ds DNA with a mercury electrode charged to
      potentials of the region T in neutral medium of relatively low ionic strength mu
      < 0.3). (i) When ds DNA is adsorbed, a significantly higher number of DNA
      segments is anchored in the positively charged electrode surface than in the
      surface bearing a negative charge, (ii) In the region T, especially adsorbed
      labile regions of ds DNA are opened in the electrode surface, which are present
      in ds DNA already in the bulk of the solution, (iii) In the narrow region of
      potentials in the Vicinity of the zero charge potential a higher number of ds DNA
      segments can be opened, probably as a consequence of the strain which could act
      on the ds DNA molecule in the course of the segmental adsorption/desorption
      process.

PMID- 16997235
TI  - Thermochemistry of aqueous solutions of alkylated nucleic acid bases. III.
      Enthalpies of hydration of uracil, thymine and their derivatives.
AB  - Enthalpies of sublimation DeltaH(0)(subl) crystalline uracil, thymine and their
      methylated derivatives as well as of N,N-diethylthymine were determinated by the
      quartz-resonator method and mass spectrometry. Enthalpies of solution at infinite
      dilution DeltaH(0)(sol) in water of aBcylated compounds were obtained
      calorimetrically. Hence the calculated enthalpies of hydration:
      DeltaH(0)(hydrsubal) = DeltaH(0)(sol) - DeltaH(0)(subl), were corrected for
      energies of cavity formation in pure liquid water to yield enthalpies of
      interaction DeltaH(0)(sint) of the solutes with their hydration shells. For
      uracil DeltaH(0)(int) = -59.8 kJ mole(-1) was obtained in this way. This value
      decreased linearly on N-methyl substitution with a mean increment of about 6.5 kJ
      mole CH2(-1). After C(5) or C(6) ring substitution it increased by about 3 kJ.
      These results are discussed in connection with heat of dilution data and
      theoretical schemes of hydration.

PMID- 16997236
TI  - Jahn-Teller effect in biomolecules.
AB  - The role played by the Jahn-Teller effect for a correct interpretation of the
      spectroscopic and structural data of some biological systems is stressed and a
      short review of the investigations so far performed is presented. Afterwards, on
      the basis of the angular overlap model, several expressions are given for the
      coupling constants of the transition metal ions, which mainly occur in
      biomolecules (Fe, Co, Cu, Mo) in order to have an approximate evaluation of the
      Jahn-Teller effect magnitude. The above expressions are then applied to obtain
      the vibronic coupling constants of the deoxygenated hemoglobin and myoglobin. The
      results obtained are compared with the predictions previously made by the author
      on these systems.

PMID- 16997237
TI  - Calculated sedimentation ratios for assemblies of two, three, four, and five
      spatially equivalent protomers.
AB  - Sedimentation ratios of oligomeric structures containing from two to five
      protomers in spatially equivalent positions are calculated on the basis of
      equations derived by Kirkwood. A range of oblate and prolate protomers and a
      systematic set of assembly modes is considered for each type of oligomer. The
      results are presented graphically. Dimensions in three mutually perpendicular
      directions are also given for each structure considered, in a format which allows
      calculation in A of the dimensions of appropriate models for actual molecules.
      Together with the results for hexameric aggregates presented previously these
      data allow sedimentation velocity measurements with any oligomer, up to and
      including the hexamer, to be analysed readily and systematically in terms of
      quaternary structure.

PMID- 16997238
TI  - Application of calculated sedimentation ratios in the specification of models for
      protein dimers, trimers, tetramers and pentamers.
AB  - In the preceding paper a systematic method for delineating quaternary structures
      compatible with the sedimentation behaviour of oligomeric assemblies was
      developed. In this companion paper the approach is illustrated by its application
      to a number of oligomeric proteins, namely beta-lactoglobulin, aminoacyl
      transferase, succinic semialdehyde dehydrogenase, arginine decarboxylase, and the
      arthropod hemocyanins. Structures of these proteins based on comparisons of
      calculated and experimental sedimentation coefficients are presented and,
      wherever possible, compared with those obtained by other techniques. The
      usefulness and limitations of the method are assessed. It is concluded that the
      sedimentation analysis will usually yield a reasonably good representation of the
      mode of assembly of protein molecules in oligomeric structures if accurate
      experimental data are available. A high degree of resolution of structural detail
      is not expected and since, in addition, the sedimentation ratio method is seldom
      definitive to one structure, it is most valuable when used in a conformatory or
      eliminative way with results from techniques more specifically designed for
      structure determination.

PMID- 16997239
TI  - Thermal transition of core particle is not a two-state process.
AB  - Thermal transition of core particle which occurs before melting of DNA and can be
      followed by circular dichroism is not a two-state process; it is the result of
      two processes which cannot be dissociated in static experiments: unfolding of
      core particles is immediately followed by their aggregation. It is thus
      impossible to get thermodynamic parameters of core particle unfolding from its
      thermal transition monitored by circular dichroism. Thermal denaturation kinetics
      of core particles gives some information about their stability. Finally core
      particle structure is more stable in chromatin than in its isolated state.

PMID- 16997240
TI  - Estimation of bound quaternary ammoniumion to a rod-like polyion with a large
      alkyl residue.
AB  - The amount of quaternary ammonium ion (Bu4N+), which is believed not to be bound
      to general carboxylpolyelectrolytes, bound to poly(iso BVE-co-MA) was estimated
      by conductivity measurements. In the region of the density of polyion charge in
      which the polyions are thought to take a free drain'ng conformation, it has been
      confirmed that the activity coefficient of Bu4N+ ions is less than 0.5 in the
      presence of a small amount of Bu4NCl, showing that the force between the
      counterions and the polyion is probably due to the hydrophobic interaction.
      Moreover, from the electrophoretic mobility Up of the polyion observed from the
      data of conductivity, it has been ascertained that Up of this polyion is two
      times larger than PAA, and the behavior of the quantity e/xiP with changing
      degree of ionization corresponds to that of the viscosity.

PMID- 16997241
TI  - Membrane potential fluctuation in Paramecium.
AB  - The fluctuation of the membrane potential in Paramecium caudatum cells was
      measured. The fluctuation was very large and composed of slow and periodic
      components and fast and random ones. The power of fast fluctuation depended on
      the environmental salt condition, particularly on the ratio of the potassium ion
      concentration to the square root of the calcium ion concentration,
      [K+]o/[Ca2+]o(1/2), in the medium. The power greatly increased with the decrease
      of this ratio. The power density spectrum of fluctuation was of the 1/(1 +
      (f/fc)2) type when the total power was large. There, the fluctuation arose mainly
      from the local current of potassium ions. Some cooperation among potassium
      channels to increase the fluctuation was suggested. The spectrum became of the
      1/f type when the total power was small.

PMID- 16997242
TI  - The role of the ionic environment in the orientation of nucleic acids in electric
      fields.
AB  - The relationship between polyelectrolyte theories based on linear charge density
      models and the electric-field induced orientation of the polyelectrolytes,
      poly(A), poly(C) and DNA is examined by varying their ionic environment with
      respect to ionic strength and acidity. The degree of counterion condensation on
      the polyelectrolytes predicted by the theories of Manning and Record is shown to
      be related linearly to the orientation as measured by their dichroism in the
      field. Micro-structural differences between poly(A) and poly(C) account for the
      differences in their dependence on the pH of the medium which affects the
      counterion condensation and thus the polarization in the orienting electric
      fields. The results consequently support recent treatments of linear
      polyelectrolytes having a high charge density which model them as smoothly
      charged linear polyions, but indicate that these models are insufficient to
      account for some of the effects of microstructural variations.

PMID- 16997243
TI  - Ionic strength and counterion repulsion as factors in the behavior of polyions in
      orienting electric fields.
AB  - The effect of counterion-counterion repulsion on the orientation of DNA, a
      polyion of high charge density is examined by electric-field orientation
      experiments. The charge species of the counterion and the ionic strength effect
      the orientation in a manner consistent with a theoretical treatment of the
      polarization of high charge density polyelectrolytes in terms of the effect of
      the applied field on the equilibrium distribution of condensed counterfoils on
      the polyion.

PMID- 16997244
TI  - Time difference scanning gel chromatography: computer simulations.
AB  - The time difference profile method of gel scanning chromatography developed by
      Brumbaugh, Saffen and Chun (Biophysical Chemistry, 1979) has been examined by
      computer simulation. The method is found to produce values for centroid movements
      that mimic those of the system being examined but are not quantitatively correct.
      In all cases the time differential "centroid" is larger than that of the
      concentration derivative (true) centroid and move at a rate slightly faster than
      the true centroids. This faster rate slowly decreases towards the true rate but
      does not approach it within reasonable times. This distorted movement reflects
      the distorted emphasis given to the larger species in the time differential
      method. The time difference method has been shown to give an adequate measure of
      the axial dispersion coefficient, L, for single species systems.

PMID- 16997245
TI  - A morphogen gradient model for pattern regulation. I. Formation of non-repetitive
      and repetitive structures.
AB  - A model for pattern formation is proposed based on two concentration gradients S
      and Sigma. S is a local morphogen generated by a reaction-diffusion mechanism
      while Sigma is a by-product of the S-decomposition. Under certain conditions S is
      well approximated by S(x,L) = alpha(L)f(x L ), where alpha(L) is a scaling
      function of the length L and f(x L ) is a monotonie function of the relative
      distance x L from the origin. Sigma degradates and diffuses in the field,
      reaching a stable L-dependent homogeneous distribution. An allosteric protein P
      with several active sites reacts with S and Sigma and separates the field into
      segments. To every segment a corresponding active state of P is dominant. Pattern
      regulation is automatically achieved since the compartmerttal separation depends
      explicitly only on x L . For the case of repetitive patterns, a supplementary
      Gierer-Meinhardt mechanism is introduced for activator X and inhibitor Y. The
      level of Sigma can affect the decomposition rate of X or Y, e.g. via a second
      order degradation reaction, hence making the chemical wavelength lambda size
      dependent. For a particular decay scheme of Y, a variation of L induces a change
      of lambda so that finally the number of repetitive structures becomes independent
      of the field size.

PMID- 16997246
TI  - A morphogen gradient model for pattern regulation. II. Time description of global
      morphogen formation and field compartmentalization.
AB  - In a model for pattern regulation, use was made of local and global morphogens S
      and Sigma. Sigma is produced from the S-degradation and it is decomposed by first
      order kinetics while it diffuses along the field. We solve exactly the partial
      differential equation for the distribution of Sigma in one spatial dimension when
      its source S is monotonie (for simplicity, linear or generally a power function).
      Assuming that S and Sigma react reversibly with an allosteric protein P according
      to a sequential scheme, we derive the evolution in time of the field separation
      into compartments. At equilibrium the relative extent of each compartment is
      constant (for variable field size) and so pattern regulation is achieved.

PMID- 16997247
TI  - The development of an equation for the potentiometric titration of linear
      polyelectrolytes using a site model.
AB  - An equation for the potentiometric titration of linear polyelectrolytes is
      derived by considering neighbor interactions of ionizable groups and the
      association equilibria between ionized groups and counterions. The first, second,
      ... and lth neighbor interactions are directly introduced into the equation, and
      additional neighbor interactions together with interactions between the ionizable
      groups and simple salt ions are taken into account as perturbed electrostatic
      potentials. It is observed that the approximation which includes the second or
      third neighbor interaction is sufficient for description of the potentiometric
      titration. Good agreement between predictions of the present theory and
      experiment is obtained for isotactic and syndiotactic poly(acrylic acids).

PMID- 16997248
TI  - Determination of ligand-binding constants by isoelectric focusing. Generalization
      and extension of theory.
AB  - The theory of a proposed isoelectric focusing procedure for the determination of
      ligand binding constants has been generalized (via numerical calculations) to non
      linear, electrophoretic velocity profiles and systems for which the change in
      velocity of the protein accompanying ligand binding depends upon pH. The theory
      has also been extended to include binding of ligand to heterogeneous sites.
      Determination of accurate values of the binding parameters depends upon
      extrapolation of apparent parameters to infinite dilution of protein.

PMID- 16997249
TI  - Conformation studies of 13 trinucleoside diphosphates by 360 MHz PMR
      spectroscopy. A bulged base conformation. I. Base protons and H1' protons.
AB  - The 360 MHz NMR spectra of the base protons and the H1 protons of thirteen
      trinucleoside diphosphates have been analyzed. The sequences chosen represent all
      purine-pyrimidine sequences. The chemical shifts of the base protons give
      evidence for strong next nearest-neighbor effects in some oligonucleotides.
      Although increasing chain length usually increases nearest-neighbor base-base
      stacking, it is not always so. Comparing ApCpG, ApUpG and GpUpG to their
      component dimers, one finds a decrease in stacking of the center pyrimidine with
      the purine on either side. The coupling constants J 1'2' also show that these
      three trimers show less stacking for their terminal residues than expected from
      their component dimers. We conclude that the sequence Pu-Py-Pu favors a
      conformation in which the pyrimidine is bulged out and the two purines stack on
      each other.

PMID- 16997250
TI  - Simultaneous rapid estimation of sedimentation coefficient and molecular weight.
AB  - Data obtained from the early portion of sedimentation velocity experiments may be
      analyzed to simultaneously estimate both s and s/D. The C versus r data obtained
      are analyzed using a nonlinear least squares algorithm and an approximate
      solution to the Lamm equation. This procedure was tested both with simulated
      noisy data and with experimental data obtained using ribonuclease, ovalbumin, and
      somatostatin.dodecylsulfate. The procedure assumes that both s and D are
      independent of concentration. The results suggest that optimal estimation of both
      s and s/D is obtained at values of (= 2D/(s.omega(2).r(a)(2))) in the range of
      0.002 to 0.01 and values of tau(= 2 somega(2)t) less than 0.04. Appropriate
      selection of rotor speed allows the estimation of both s and s/D for nearly
      globular macromolecules in the range of 10(4) to 10(6) daltons with data obtained
      during the first 3000-5000 seconds of a sedimentation velocity experiment.

PMID- 16997252
TI  - New method for simultaneous measurement of frequency spectra of complex
      dielectric constants of polyelectrolyte solutions.
AB  - A high-speed and high-accuracy measurement of relaxational frequency spectra of
      complex dielectric constants of polyelectrolyte solutions with a high
      conductivity was realized by a new digital signal processing technique. In this
      method, a sum of sinusoidal waves of geometrical series of frequencies is
      utilized as a multifrequency excitation signal and demodulation of the resulting
      response is carried out simply by addition and subtraction of digital signals in
      a minicomputer. This new technique is superior to the conventional cross
      correlation method using the fast Fourier transform in that it greatly reduces
      the processing time and avoids effectively the influence of a quantization error.
      The result for a DNA solution obtained by this method is presented to demonstrate
      the utility of this method.

PMID- 16997253
TI  - The release of monovalent counterions by addition of divalent counterions in
      coulombic interaction system.
AB  - The additivity rule of counterion activity or osmotic pressure in rodlike
      polyelectrolyte solutions has been discussed on the basis of the Fokker-Planck
      and Poisson equations in relation to the fluctuation of counterion distribution.
      This new theory has concluded that the additivity rule of counterion activity is
      less applicable than that of osmotic pressure due to the electric expansion force
      acting on the free-volume surface resulting from the fluctuation of counterion
      distribution. The theory has introduced an approximate relation between the
      counterion activities in the mixture solution of divalent and monovalent
      counterions, such that Deltaa+ = DeltaC++ - Deltaa++, in which Deltaa+ represents
      the increase of activity of monovalent counter-ions resulting from the addition
      of divalent counterionsDeltaC++, (in molar) to the solution, and Deltaa++ means
      the increase of the divalent counterion activity (in molar) in this process. This
      relation has been experimentally examined for Na-PSS solutions in the process of
      Cu2+ ion addition by the use of Na+ and Cu2+ sensitive electrodes, and it has
      been turned out that the relation is established in the low charge state of
      polyion.

PMID- 16997254
TI  - The relationship between the poisson-boltzmann model and the condensation
      hypothesis: an analysis based on the low salt form of the Donnan coefficient.
AB  - Two common models for the interaction of counterions with cylindrical polyions
      are considered in the context of the Donnan membrane equilibrium. General
      analytic expressions are obtained from the Poisson-Boltzmann equation for the
      Donnan coefficient in terms of the potential at the surface of the polyion or the
      local concentration of unbound ions at the surface. Analysis based on these
      expressions shows that if, and only if, the polyion charge density exceeds a
      certain critical value a large local concentration of ions will persist near the
      polyion surface at low ionic strengths. We therefore conclude that this principal
      hypothesis of the condensation model is consistent with the characteristics of
      the Poisson-Boltzmann potential at the surface of the polyion.

PMID- 16997255
TI  - Dielectric increment in polyion solutions due to the distortion of counterion
      distribution.
AB  - A theory of DC dielectric increment, delta, has been constructed based on the
      Fokker- Planck and Poisson equations on the mechanism of the distortion of
      spatial counterion distribution around a rodlike polyion under the applied
      electric field, E, perpendicular to the polyion lod. The DC dielectric constant
      of polyion solutions can be obtained analytically in the both cases of absence
      and presence of counterion-flow. The nonlinearity of the Poisson-Boltzmann
      equation in the absence of E has given the interesting behaviors of delta. The
      calculation in the absence of counterion-flow has shown the delta-values having
      the same order of magnitude as the experimental data at the higher frequency
      range (around 100 kHz), and the importance of this mechanism has been pointed
      out.

PMID- 16997256
TI  - Electric birefringence of ionized polypeptides in solution and the effect of high
      electric fields on the helix-coil transition.
AB  - Electric birefringence and circular dichroism measurements have been made on
      solutions of two po!y (L-lysine) homologs. The specific Kerr constant and the
      molar ellipticity at 222 nm of poly (L-alpha, gamma-diaminobutyric acid
      hydrochloride) in methanol/water mixtures underwent an abrupt change between 75
      and 80 vol% methanol at 25 degrees C, corresponding to a solvent-induced helix
      coil transition. On the helix side of the transition region, i.e., between 78 and
      80 vol% methanol, anomalous birefringence transients indicative of field-induced
      helix-to-coil transition were observed at high fields. In the case of poly (L
      ornithine hydrobromide) in methanol/water mixtures, a helix-coil transition was
      induced between 93 and 98 vol% methanol and anomalous birefringence transients
      were observed between 96 and 98 vol% methanol. The double logarithmic plots of
      the steady-state specific birefringence versus the square of field strength for
      various solvent compositions and polymer concentrations could be superimposed on
      one another by horizontal and vertical shifts, except for the range where
      anomalous birefringence transients were observed. This enabled us to estimate the
      threshold field strength.

PMID- 16997257
TI  - Kinetics of helix-coil transition of polypeptides in solution by the relaxation
      methods.
AB  - Relaxation phenomena were studied in aqueous solutions of poly (alpha-L-glutamic
      acid) (Glu)n and poly (alpha-L-lysine) (Lys)n under various conditions using the
      electric field pulse method with detection by conductivity change. The relaxation
      time for the (Glu)n has a maximum value at the midpoint of the helix-coil
      transition. Some possible mechanisms are discussed and the observed relaxation
      phenomenon is attributed to the helix-coil transition. In the case of (Lys)n, the
      relaxation time as a function of pH exhibits two maxima. One is assigned to a
      proton transfer reaction and the other to the helix-coil transition. Using the
      Schwarz's theory the rate constants of the helix growth step for both (Glu)n and
      (Lys)n are estimated. The difference in the activation parameters for (Glu)n and
      (Lys)n is discussed.

PMID- 16997258
TI  - Conformational transitions of the hydrophobic polyacids.
AB  - The conformational transitions of the alternating maleic acid copolymers with
      styrene (MA-St)n, and alpha-methyl styrene (MA-MSt)(n) in aqueous solutions were
      studied by means of various methods. The following results were obtained: 1) The
      conformational transitions of (MA-St)n from the compact to extended coil form are
      observed in various salt solutions, as in aqueous NaCl, and the compact form is
      stabilized by Rb+ and Cs+, but destabilized by Li+. The coions, Br-, I-, ClO4-
      and SCN- affect scarcely the stability of the compact form. 2) The temperature
      coefficient of viscosity d In [eta]/dT of (MA-St)n in 0.09 M NaCl was positive
      for the compact form, but negative for the coil form, and it reflects the
      transition. 3) The difference between specific heats for the compact and coil
      forms of (MA-St)n in 0.03 M NaCl is determined to be about 15% of the
      corresponding heat of transfer of benzene to aqueous medium. 4) A remarkable
      dilution of the bound monomeric acridine orange to the compact form (MA-St)n is
      observed and the dimerization free energy of the dye in the compact form is about
      -2.1 kcal mole at 25 degrees C. 5) Potentiometric, dilatometric and viscometric
      titrations of (MA-MSt)n in aqueous NaCl at 25 degrees C show a similar
      conformational transition to that of (MA-St)n. Also, the difference in the molar
      extinction coefficient at 261 nm indicates the transition. The compact form of
      (MA-MSt)n is more unstable than that of (MA-St)n. From the results, the compact
      conformations and the transition mechanism of both the polyacids were discussed
      in comparison with the results for the maleic acid copolymers with n-alkyl vinyl
      ethers.

PMID- 16997259
TI  - Thermodynamics of hydrophobic polyacids.
AB  - The thermodynamics of deprotonating hydrolyzed 1-1 copolymers of maleic anhydride
      with pentyl, hexyl and octyl vinyl ether was investigated by calorimetric and
      potentiometric methods. These polyacids undergo a transition from a compact to a
      random coil conformation upon ionization in aqueous media. The results were
      compared with those obtained previously for similar copolymers with smaller alkyl
      side-chains. The contributions of the enthalpy and entropy to the free energy
      were analyzed. The major effects appeared to be related to the charging of the
      compact form of the polyacids, the electrostriction of water by the completely
      ionized dicarboxylate groups and the reorganization of water around newly exposed
      alkyl side-chains arising from the conformational transition.

PMID- 16997260
TI  - Dielectric dispersion of alternating copolymers of maleic acid.
AB  - Dielectric dispersions of three kinds of copolymers of maleic acid, poly (maleic
      acid-co-methyl vinyl ether) (PMAMVE), poly(maleic add-co-ethyl vinyl ether)
      (PMAEVE) and poly (maleic acid-co-styrene) (PMAST), were measured by use of a
      pseudorandom noise dielectric spectrometer. A large dielectric increment was
      observed in the low frequency region (10-20 Hz), and was explained in terms of
      our theory of ion fluctuation. When these copolymers were neutralized with
      mixtures of NaOH and Ca(OH)2 by changing their ratio, enhancement of the static
      dielectric increment was observed in the intermediate ratios of both ion species.
      This phenomenon was analyzed by modifying our. theory of ion fluctuation to the
      case of alternating copolymers. Quantitative agreement with experimental results
      was obtained by using values of parameters representing binding energies and
      mutual repulsion, which are chosen to fit the calculated degree of ion binding to
      the experimental data on activities of Na+ and Ca2+ ions. At large fractions of
      divalent ions, the increment, relaxation time and specific viscosity were found
      to decrease sharply due to chelation by divalent ions.

PMID- 16997261
TI  - Dynamic properties of concentrated suspensions of charged polystyrene spheres.
AB  - Ordered structure formation of charged polystyrene spheres was studied by
      measuring the order-disorder phase diagrams as well as the mechanical properties.
      The phase diagrams indicate that the ordering of polystyrene spheres obeys
      Lindemann's law of crystal melting, in which the Lindemann's parameter is about
      5%. The rigidity of about 10(3) dyn/cm(2) was observed in the ordered suspension
      of polystyrene spheres as measured by a torsional quartz crystal method. The
      steady flow properties of suspensions of polystyrene spheres showed a remarkable
      change from a Bingham body to a Newtonian liquid at the transition point. The
      limit of elasticity in the ordered phase was about 1 dyn/cm(2). The viscosity in
      the disordered phase was well explained by the free volume theory of liquids. It
      is concluded from these facts that the ordered phase of polystyrene spheres is a
      real "crystal" whereas the disordered phase is a "liquid". Properties of ordered
      structures in biological systems are also discussed.

PMID- 16997262
TI  - Size and shape of charged micelles of ionic surfactants in aqueous salt
      solutions.
AB  - Light-scattering has been measured on aqueous NaCl solutions of
      dodecyldimethylammonium chloride and sodium dodecyl sulfate. From molecular
      weight determination it is confirmed that spherical micelles are formed at low
      NaCl concentrations, but at high NaCl concentrations the small micelles formed at
      the critical micelle concentration further associate to form large rod-like
      micelles with increasing micelle concentration. The reduction of repulsion
      between charged groups induces the sphere-rod transition of micelle shape. The
      dependence of molecular weight on ionic strength can be expressed by double
      logarithmic relations, which are dependent on the micelle shape. While
      dodecyldimethylammonium chloride dissolves even in 4.00 M NaCl, sodium dodecyl
      sulfate solutions exhibit some XXX in angular dissymmetry at NaCl concentrations
      higher than 0.50 M at low temperatures.

PMID- 16997264
TI  - New outlook on polymer "catalysis".

PMID- 16997263
TI  - A conductance stopped-flow study of polyelectrolyte systems. Dynamic
      conformational change of synthetic macroions and their complexation with neutral
      polymers.
AB  - Two dynamic phenomena of polyelectrolyte systems, namely the rapid conformational
      changes of weak polyelectiolytes (polyacrylic acid (HPAA) and polyethylenimine,
      induced by pH-jump) and the complexation of HPAA with polyvinylpyrrolidone are
      first investigated by means of the conductance stopped-flow (kappa-SF) technique.
      The pH-induced relaxations observed by mixing an aqueous solution of HPAA or
      polyethylenimine with water containing a tiny amount of alkali or acid, are
      safely ascribed to the conformational transition of the macroions between the
      compact "coil" and the stretched "rod" forms. The relaxation times are large at
      high degrees of neutralization and for "rod" conformation. Tentative values for
      the thermodynamic parameters of the dynamic conformational changes are obtained
      and discussed. The reaction rates of the polymer complex formation and
      dissociation of HPAA with polyvinylpyrrolidone are also determined using the
      kappa-SF method. The association constant and the rates of formation and
      dissociation are 1.84 x 10(3) M(-1), 9.4 x 10(4) M(-1) s(-1) and 51 s(-1) at 10
      degrees C, respectively. We then derive the thermodynamic parameters from the
      above results.

PMID- 16997265
TI  - Light scattering from solutions of a semi-flexible polymer and a polyelectrolyte
      both having sharp molecular weight distributions.
AB  - The particle scattering factor in light scattering is determined for poly(tert
      butyl crotonate) in n-butyl chloride and also for partially neutralized poly
      (acrylic acid) in aqueous solution in the presence of added neutral salt (NaBr).
      The former is a wormlike chain which is extended due to stiffness of the polymer
      chain, while the latter is extended due to the electrostatic repulsive force
      which is a kind of excluded volume effect. A clear difference is found between
      P(theta) of both polymers.

PMID- 16997266
TI  - Membrane biophysics of chemoreception and taxis in the plasmodium of Physarum
      polycephalum.
AB  - The threshold phenomena observed in chemoreception and taxis of the plasmodium of
      Physarum polycephalum were analyzed on the basis of physical chemistry. Various
      physicochemical concepts and rules, e.g. the Schulze-Hardy rule, the lyotropic
      number and the hydrophobic interactions, were shown to be applicable reasonably
      well to the physiological functions in Physarum. It was stressed that the
      structural change of the surface membrane induced by reception of chemical
      stimuli plays a decisive role in recognition and sensitivity to the external
      stimuli as well as the appearance of tactic movement in the amoeboid motility of
      Physarum.

PMID- 16997267
TI  - The effect of roundabout design features on cyclist accident rate.
AB  - Roundabouts are known to result in fewer traffic accidents than traditional
      intersections. However, this is to a lesser degree true for bicycles than for
      vehicles. In this paper, we aimed at establishing statistical relationships
      through Poisson regression and logistic regression analyses between yearly rate
      of cyclist accidents on one hand and roundabout geometry, age and traffic volume
      (vehicles and cyclists) on the other. We related all roundabout cyclist accidents
      recorded by the hospital emergency department of the town of Odense, Denmark,
      through the years 1999-2003 (N=171) to various geometric features, age and
      traffic volume of all roundabouts on the Danish island of Funen (N=88). Cyclist
      and vehicle volumes turned out to be significant predictors in most of our models
      the higher the volumes, the more accidents. Moreover, potential vehicle speed was
      a significant predictor, and so was age of the roundabout-older roundabouts
      related to more accidents and higher accident probability. Excluding 48 single
      cyclist accidents strengthened the relationship between accidents on one hand and
      vehicle and cyclist volume and potential vehicle speed on the other. This
      stresses the significance of speed and traffic volume for traffic accidents with
      more than one partner involved. The 48 single cyclist accidents were
      significantly related to the traffic volume of cyclists only. Due to our limited
      number of observations, the models should be regarded as indicative.

PMID- 16997268
TI  - A combined school- and community-based campaign targeting all school-age children
      of Burkina Faso against schistosomiasis and soil-transmitted helminthiasis:
      performance, financial costs and implications for sustainability.
AB  - A combined school- and community-based campaign targeting the entire school-age
      population of Burkina Faso with drugs against schistosomiasis (praziquantel) and
      soil-transmitted helminthiasis (albendazole) was implemented in 2004-2005. In
      total, 3,322,564 children from 5 to 15 years of age were treated, equivalent to a
      90.8% coverage of the total school-age population of the country. The total costs
      of the campaign were estimated to be US 1,067,284 dollars, of which 69.4% was
      spent on the drugs. Delivery costs per child treated were US 0.098 dollar, in the
      same range as school-based only interventions implemented in other countries;
      total costs per child treated (including drugs) were US 0.32 dollar. We conclude
      that a combined school- and community-based strategy is effective in attaining a
      high coverage among school-age children in countries where school enrolment is
      low and where primary schools cannot serve as the exclusive drug distribution
      points. The challenge for Burkina Faso will now be to ensure the sustainability
      of these disease control activities.

PMID- 16997269
TI  - Foam formation and mitigation in a three-phase gas-liquid-particulate system.
AB  - Foaming is of great concern in a number of industrial processes involving three
      phase gas-liquid-finely divided solid systems such as those encountered in the
      vitrification of highly radioactive nuclear waste slurries and sludges. Recent
      work has clearly shown that the surface properties of the particles such as
      hydrophilicity, hydrophobicity or biphilicity (i.e. partially wetted by water)
      are the cause of foamability and foam stability. The literature data on particles
      causing foaminess and foam stability in the absence of any surfactant are rather
      scarce. This paper presents experimental observations on aqueous foams with
      polyhedral structures containing over 90% air generated due to the presence of
      irregularly-shaped fine crystalline particles of sodium chloride which were
      modified into amphiphilic particles by physical adsorption of a cationic
      surfactant. Cross-polarized light microscopy was used to visualize the physical
      adsorption of the surfactant on the crystal surface. It is shown that these
      biphilic or amphiphilic particles attach to the air bubble surface and prevent
      the coalescence of bubbles, thereby extending the life of the foam. The foaming
      power of solid particles increases with an increase in the concentration of
      amphiphilic particles, and a maximum in foaminess is observed which is due to two
      competing effects. Amphiphilic particles promote foamability by attachment to the
      bubble surfaces as individual particles and foam inhibition due to the clustering
      or flocculation of particles in the bulk at high particle concentrations. We
      studied the adsorption of amphiphilic particles at a planar air-water surface and
      found that the degree of foamability correlates well with the particle coverage
      (i.e. adsorption density) at the air-liquid surface. An exploratory study was
      also conducted using an antifoam recently developed by IIT researchers to
      mitigate foaming in particle-laden gas-liquid systems.

PMID- 16997270
TI  - Fission yeast Mcl1 interacts with SCF(Pof3) and is required for centromere
      formation.
AB  - The fission yeast S-phase regulator Mcl1, an orthologue of budding yeast Ctf4, is
      an interacting protein of DNA polymerase alpha and an important factor to ensure
      DNA replication and sister chromatid cohesion. Deletion of this protein results
      in severe cohesion defects, however, the function and cellular role of this
      protein remains elusive. In this study we isolate Mcl1 as an interaction partner
      of the F-box protein Pof3, which is a component of the ubiquitin ligase complex
      SCF(Pof3). Comparing the phenotypes of cells lacking pof3+ or mcl1+ we find a
      broad overlap including the accumulation of DNA damage and activation of the DNA
      damage pathway. Importantly, we identity a novel, specific role for Mcl1 in the
      transcriptional silencing and the localisation of CENP-A at the centromeres.

PMID- 16997271
TI  - Analysis of neuron-like differentiation of human bone marrow mesenchymal stem
      cells.
AB  - The objective of the study was to evaluate differentiation of human bone marrow
      mesenchymal stem cells into true or pseudo neurons after treating with chemical
      induction medium in vitro. The morphological changes were assessed using
      interference contrast microscopy. Immunocytochemistry and Western blotting were
      performed using neuronal markers. Further evaluation was conducted with proteomic
      profiling, DNA microarray analysis and the whole-cell patch clamp test. After
      three hours of treatment with chemical induction medium, nearly three-fourths of
      the hMSCs changed to cells with a neuronal phenotype. The results of
      immunocytochemistry and Western blotting showed a high expression of neuronal
      markers in these cells at 3 h which decreased at 24 h. The proteomics analysis
      showed no change of proteins related to neuronal differentiation. DNA microarray
      showed downregulation of neuron related genes. The patch clamp test was unable to
      demonstrate any similarity to true neurons. Our findings suggest that neuron-like
      cells derived from chemical induction of hMSCs are not the genuine neurons as
      they resemble true neurons phenotypically but are different in genotypic and
      electrophysiological characteristics.

PMID- 16997272
TI  - Shift syndecan-2 from RACK1 to caveolin-2 upon transformation with oncogenic ras.
AB  - Syndecan-2 was found to detach from RACK1 and associate with caveolin-2 and Ras
      in cells transformed with oncogenic ras. Most of syndecan-2 from transformed
      cells was revealed with negligible phosphorylations at tyrosine residues. We
      experimented with HeLa cells transfected with plasmids encoding syndecan-2 and
      its mutants (syndecan-2(Y180F), syndecan-2(Y192F), and syndecan-2(Y180,192F)) to
      provide evidences that PY180 of syndecan-2 is a binding site for RACK1 and is
      deprived in cells transfected with oncogenic ras. However, in HeLa cells
      transfected with syndecan-2(Y180F), RACK1 was found to sustain its reactions with
      syndecan-2 independent of phosphorylation. The finding of syndecan-2 reactive
      with caveolin-2/Ras suggests the molecular complex most likely to obstruct RACK1
      for functional attachment at syndecan-2, as revealed in cells transfected with
      oncogenic ras. We provided evidences to reinforce the view that molecular
      rearrangements upon transformation are specific and interesting.

PMID- 16997273
TI  - Metabolism of 5-hydroxy-6,8,11,14-eicosatetraenoic acid by human endothelial
      cells.
AB  - There is increasing evidence that proinflammatory products of the 5-lipoxygenase
      pathway play an important role in cardiovascular disease. In the present study,
      we found that human endothelial cells rapidly oxidize the 5-lipoxygenase product
      5S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) to 5-oxo-6,8,11,14
      eicosatetraenoic acid (5-oxo-ETE), a potent chemoattractant for myeloid cells. 5
      Oxo-ETE synthesis is strongly stimulated by oxidative stress. This effect is
      enhanced following inhibition of the pentose phosphate pathway with
      dehydroepiandrosterone and is mimicked by diamide, which oxidizes intracellular
      GSH to GSSG. Conversely, it is blocked by depletion of intracellular GSH/GSSG.
      The kinetics of H2O2-induced 5-oxo-ETE synthesis by endothelial cells correlate
      well with changes in the intracellular levels of GSSG and NADP+. These results
      suggest that exposure of the endothelium to oxidative stress and inflammation
      could result in the synthesis of 5-oxo-ETE, which could then induce the
      infiltration of inflammatory cells into the tissue.

PMID- 16997274
TI  - Expression of the Saccharomyces cerevisiae PIS1 gene is modulated by multiple
      ATGs in the promoter.
AB  - The PIS1 gene encodes a key branchpoint phospholipid biosynthetic enzyme,
      phosphatidylinositol synthase. The PIS1 promoter contains the unusual feature of
      three ATG codons (ATGs1, 2, and 3) in-frame with three stop codons, located just
      before the authentic start codon (ATG4). Using a PIS1(promoter)-lacZ reporter
      expression system and site-directed mutagenesis, we investigated the role the
      "upstream" ATG codons play in modulation of PIS1 expression. Of the single codon
      changes, mutation of the first ATG (ATG1) resulted in the largest increase of the
      reporter gene PIS1(promoter)-lacZ expression. All combinations of altered
      upstream ATG codons also resulted in greater reporter expression. Reverse
      transcription-PCR revealed that at least some PIS1 transcripts include all AUG
      codons, and their synthesis is probably directed by a second TATA box upstream of
      the putative TATA box. These results indicate that the multiple upstream AUG
      codons are present in at least some PIS1 transcripts and negatively impact PIS1
      expression.

PMID- 16997275
TI  - Measurement of the adhesive force between a single Klebsiella pneumoniae type 3
      fimbria and collagen IV using optical tweezers.
AB  - Type 3 fimbriae are important adhesive filaments that assist Klebsiella
      pneumoniae to establish an infection. Different MrkD adhesin variants on the
      fimbriae are known to display distinct adherence capability for the bacteria to
      bind extracellular matrix proteins, although the difference has not been
      determined physically. For this reason, the adhesive force between type 3
      fimbriae and collagen IV were measured using optical tweezers. The measured force
      data displayed a periodic histogram thus Fourier analysis was applied to group it
      to extract the adhesive force of a single molecular pair. Specifically, we showed
      that grouping should begin with an offset at the first half of the period.
      Finally, we first present the adhesive force between each mrkD(V2)-, mrkD(V3)-,
      and mrkD(V4)-expressed fimbriae and collagen IV is 2.03, 3.79, and 2.87 pN,
      respectively. This result can be referred to further research on mrkD allelic
      effect on bacteria infection.

PMID- 16997276
TI  - Attenuation of oxidative stress and cardiac dysfunction by bisoprolol in an
      animal model of dilated cardiomyopathy.
AB  - Oxidative stress is an important susceptibility factor for dilated
      cardiomyopathy. We have investigated the effects of bisoprolol, a beta1-selective
      adrenoceptor blocker, on oxidative stress and the development of cardiac
      dysfunction in a model of dilated cardiomyopathy. Male TO-2 and control hamsters
      at 8 weeks of age were treated with bisoprolol (5 mg/kg per day) or vehicle for 4
      weeks. Treatment with bisoprolol prevented the progression of cardiac dysfunction
      in TO-2 hamsters. This drug did not affect the increase in NADPH oxidase activity
      but prevented the reduction in activity and expression of mitochondrial manganese
      dependent superoxide dismutase as well as the increases in the concentrations of
      interleukin-1beta and tumor necrosis factor-alpha in the left ventricle of TO-2
      hamsters. Attenuation of the development of cardiac dysfunction by bisoprolol may
      thus result in part from normalization of the associated increases in the levels
      of oxidative stress and pro-inflammatory cytokines in the left ventricle.

PMID- 16997277
TI  - Insulin and nateglinide reduce monocyte adhesion to endothelial cells in Goto
      Kakizaki rats exhibiting repetitive blood glucose fluctuation.
AB  - Epidemiological studies demonstrated the importance of postprandial hyperglycemia
      on the progression of atherosclerosis. However, whether treatment of postprandial
      hyperglycemia by insulin or insulin secretagogues has a beneficial effect on
      atherosclerosis has not been elucidated. To elucidate the effects of reduction of
      postprandial rise of blood glucose by insulin and nateglinide on monocyte
      adhesion to endothelial cells, we used non-obese type 2 diabetic Goto-Kakizaki
      (GK) rats fed twice daily, as a model of repetitive postprandial hyperglycemia.
      We investigated the effects of insulin injection and nateglinide administration
      just before each meal for 12 weeks on monocyte adhesion to endothelial cells. By
      setting the doses of insulin and nateglinide, both treatment significantly
      reduced postprandial hyperglycemia without significant reduction of HbA1c.
      Nateglinide also reduced serum insulin level just after 1 h meal. Both
      nateglinide and insulin therapy reduced the number of monocytes adherent to the
      aortic endothelial layer. Nateglinide, but not insulin, reduced intimal thickness
      of the thoracic aorta. While increased serum insulin level might be regarded as a
      factor responsible for the progression of atherosclerosis, our data showed that
      treatment with pre-meal insulin or nateglinide, which reduces postprandial
      hyperglycemia, reduced monocyte adhesion to endothelial cells.

PMID- 16997278
TI  - Co-localization of the alpha-subunit of BK-channels and c-PLA2 in GH3 cells.
AB  - Large conductance, calcium-activated potassium channels (maxi K- or BK-channels)
      can be regulated by arachidonic acid produced by c-Phospholipase A2 (c-PLA2).
      Since in every excised patch from GH3 cells where there was BK-channel activity,
      treatment with either a stimulator or inhibitor of c-PLA2 resulted in a
      corresponding increase or decrease in BK-channel activity, we hypothesized that
      there must be a close association between BK-channel proteins and c-PLA2 in the
      cell membrane. To test this hypothesis, we first determined whether the two
      proteins would co-immunoprecipitate. We then used confocal imaging of
      fluorescently tagged proteins to determine where in the cells BK-channel proteins
      and c-PLA2 co-localize. The alpha-subunit of the BK-channel was strongly co
      immunoprecipitated by c-PLA2 antibodies, suggesting that most of the BK channel
      alpha-subunits are associated with c-PLA2. This interaction was not affected by
      pharmacologically inhibiting c-PLA2 suggesting that the association does not
      require functionally active c-PLA2. Following dual immunohistochemical labeling
      and confocal microscopy, image analysis revealed that in the cytosol there was
      some co-localization, but most of the c-PLA2 was separate from BK-channel
      proteins. On the other hand, the c-PLA2 and BK-channel proteins at the plasma
      membrane were strongly co-localized. Immunoprecipitation experiments conducted
      with plasma membrane proteins support these findings. We conclude that c-PLA2 is
      likely physically associated with BK-channel proteins at the cell surface.

PMID- 16997279
TI  - Conformational analysis in solution of gastrin releasing peptide.
AB  - Gastrin releasing peptide (GRP) is the first peptide isolated from porcine
      gastric and intestinal tissues and is homologous to the carboxyl terminus of
      bombesin (Bn) isolated from the skin of the frog Bombina bombina. It is a member
      of the Bn-like peptides, which are important in numerous biological and
      pathological processes. The Bn-like peptides show high sequence homology in their
      C-terminal regions, but they have different selectivity for their receptors. In
      particular, GRP selectively binds to the GRP receptor (GRPR). However, the
      molecular basis for this selectivity remains largely unknown. Here, we report the
      three-dimensional structure of GRP. Hopefully, it could be helpful in a better
      understanding of the binding selectivity between GRP and GRPR.

PMID- 16997280
TI  - Histone acetyltransferase HBO1 inhibits NF-kappaB activity by coactivator
      sequestration.
AB  - The MYST acetyltransferase HBO1 is implicated in the regulation of DNA
      replication and activities of transcription factors such as the androgen
      receptor. Since the androgen receptor and NF-kappaB transcription factors
      crossmodulate their transcriptional activity, we investigated whether HBO1
      regulates NF-kappaB signaling. Here, we report that in 293T cells HBO1 reduced
      dose-dependently NF-kappaB activity stimulated by TNFalpha, or by overexpressing
      p65/RelA, RelB, or cRel. Mutational analysis showed that the N-terminal serine
      rich region of HBO1 but not the acetyltransferase function was required for
      inhibition. Electrophoretic mobility-shift assays demonstrated that HBO1 was
      neither perturbing the formation of p65/RelA DNA complexes nor binding itself to
      the kappaB consensus sequence or to p65/RelA, suggesting that HBO1 reduced NF
      kappaB activity by squelching a cofactor. These data establish a novel function
      for HBO1 showing that it reduced NF-kappaB activity by sequestrating an essential
      coactivator from the NF-kappaB transcriptional complex.

PMID- 16997281
TI  - Contribution of P2X1 receptor intracellular basic residues to channel properties.
AB  - The intracellular amino and carboxy termini of P2X receptors have been shown to
      contribute to the regulation of ATP evoked currents. In this study we produced,
      and expressed in Xenopus oocytes, individual alanine point mutants of positively
      charged amino acids (eight lysine, seven arginine and one histidine) in the
      intracellular domains of the human P2X1 receptor. The majority of these mutations
      had no effect on the amplitude, time-course or rectification of ATP evoked
      currents. In contrast the mutant K367A was expressed at normal levels at the cell
      surface however ATP evoked currents were reduced by >99% and desensitised more
      rapidly demonstrating a role of K367 in channel regulation. This is similar to
      that previously described for T18A mutant channels. Co-expression of T18A and
      K367A mutant P2X1 receptors produced larger ATP evoked responses than either
      mutant alone and suggests that these amino and carboxy terminal regions interact
      to regulate channel function.

PMID- 16997282
TI  - NF-kappaB functions in the nervous system: from development to disease.
AB  - The transcription factor nuclear factor-kappaB (NF-kappaB) is an ubiquitously
      expressed dimeric molecule with post-translationally regulated activity. Its role
      in the immune system and host defense has been well characterized over the last
      two decades. In contrast, our understanding of the function of this transcription
      factor in the nervous system (NS) is only emerging. Given their cytoplasmic
      retention and nuclear translocation upon stimulus, NF-kappaB members are likely
      to exert an important role in transduction of signals from synaptic terminals to
      nucleus, to initiate transcriptional responses. This report describes recent
      findings deciphering the diverse functions of NF-kappaB in NS development and
      activity, which range from the control of cell growth, survival and inflammatory
      response to synaptic plasticity, behavior and cognition. Particular attention is
      given to the specific roles of NF-kappaB in the various cells of the NS, e.g.
      neurons and glia. Current knowledge of the contribution of NF-kappaB to several
      neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's
      diseases is also summarized.

PMID- 16997283
TI  - Focal adhesion kinase: a potential target in cancer therapy.
AB  - Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an
      important role in signal transduction pathways that are initiated at sites of
      integrin-mediated cell adhesions and by growth factor receptors. FAK is a key
      regulator of survival, proliferation, migration and invasion: processes that are
      all involved in the development and progression of cancer. FAK is also linked to
      oncogenes at both a biochemical and functional level. Moreover, overexpression
      and/or increased activity of FAK is common in a wide variety of human cancers,
      implicating a role for FAK in carcinogenesis. Given the important role of FAK in
      a large number of processes involved in tumorigenesis, metastasis and survival
      signalling FAK should be regarded as a potential target in the development of
      anti-cancer drugs. Therefore, selective inhibitors of FAK need to be developed.
      Combination of these selective FAK inhibitors with cytotoxic agents could be a
      very promising anti-cancer therapy.

PMID- 16997284
TI  - The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's
      disease.
AB  - BACKGROUND: Few data are currently available investigating neurosteroids (NS) in
      Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and
      plasma in patients with AD, but it is unclear if allopregnanolone is also reduced
      in brain. Because a number of NS exhibit neuroprotective effects and impact
      cognitive performance in rodent models, these molecules may be relevant to the
      pathophysiology of neurodegenerative disorders. We therefore investigated
      prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels
      (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined
      in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male
      control subjects by gas chromatography/mass spectrometry preceded by high
      performance liquid chromatography purification. RESULTS: Subjects with AD exhibit
      significant reductions in allopregnanolone compared with cognitively intact
      control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p =
      .02). Allopregnanolone levels are inversely correlated with neuropathological
      disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in
      subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant
      reductions in PFC allopregnanolone levels, a finding that may be relevant to
      neuropathological disease stage severity. Neurosteroids may have utility as
      candidate biomarkers in AD.

PMID- 16997285
TI  - Electrophysiological and information processing variability predicts memory
      decrements associated with normal age-related cognitive decline and Alzheimer's
      disease (AD).
AB  - Recent theoretical models of cognitive aging have implicated increased intra
      individual variability as a critical marker of decline. The current study
      examined electrophysiological and information processing variability and memory
      performance in normal younger and older controls, and older adults with
      Alzheimer's disease (AD). It was hypothesized that higher levels of variability
      would be indicative of age-related and disease-related memory deficits. Results
      indicated both implicit and explicit memory deficits associated with AD.
      Consistent with previous research, behavioral speed and variability emerged as
      sensitive to age- and disease-related change. Amplitude variability of P3 event
      related potentials was a unique component of electrophysiological activity and
      accounted for significant variance in reaction time (RT) mean and RT standard
      deviation, which in turn accounted for significant variance in memory function.
      Results are discussed in light of theoretical and applied issues in the field of
      cognitive aging.

PMID- 16997286
TI  - Improvements in motor behavioral tests during deep brain stimulation of the
      subthalamic nucleus in rats with different degrees of unilateral parkinsonism.
AB  - Deep brain stimulation (DBS) improves motor performance in Parkinson's disease
      (PD) patients. To evaluate the effects of subthalamic nucleus (STN)-DBS on
      impaired motor behavior, we studied improvements in motor performance after
      delivery of unilateral stimulation to the STN in rats with mild and severe
      lesions of the nigrostriatal dopamine system caused by injecting 6
      hydroxydopamine into the striatum. The rats were trained and performed motor
      behavioral tests including rotational behavior test, stepping test, and rotarod
      test before and after receiving DBS. We demonstrated that stimulation at a
      current strength of 200 microA, which stopped most of the D-amphetamine-induced
      rotational behaviors in these two groups, improved movement impairments in both
      the mild and severe groups and that the improvements in the mild group were
      significantly better than those in the severe group. More experimental and
      clinical studies are needed to evaluate the efficiency of STN-DBS for different
      stages of PD.

PMID- 16997287
TI  - Adult neurological function following neonatal hypoxia-ischemia in a mouse model
      of the term neonate: water maze performance is dependent on separable cognitive
      and motor components.
AB  - BACKGROUND AND PURPOSE: Hypoxic-ischemic injury in term neonates remains a
      significant cause of long-term neurological morbidity. The post-natal day 10
      (P10) mouse is accepted as a model for the term human. This study was designed to
      assess the relationships between the duration of hypoxia-ischemia (HI) on P10 and
      the structural and functional neurological deficits that appear in the adult
      mouse as a consequence. METHODS: Post-natal day 10 129T2xC57Bl/6 F1 hybrid mice
      were subjected to 0, 45, 60 or 75 min of hypoxia-ischemia using the Rice-Vannucci
      model. Beginning on P50 these mice were tested over the next 8 weeks using zero
      maze, locomotor activity, novel object recognition, cued, hidden and reduced
      Morris water mazes, delayed probe trials and response to apomorphine injection.
      Brain weights and histology were obtained at the end of testing. RESULTS: The
      degree of structural and behavioral abnormalities in adult mice correlated with
      the duration of hypoxia-ischemia on P10. Useful behavioral tests for separating
      adult mice according to duration of hypoxia-ischemia on P10 include locomotor
      activity, the Morris water mazes and response to apomorphine. We found cued
      "learning" persisted, although latencies increased, with increasing HI time while
      spatial learning decayed as a function of HI time. Severe HI injury involving the
      ventral hippocampus resulted in excessive locomotor activity. CONCLUSIONS: After
      correcting for motor deficits, there is evidence for persistence of "cued"
      learning but not spatial learning with increasing hypoxia-ischemia time on P10 in
      this model system.

PMID- 16997288
TI  - An electrophysiological study of mood, modal context, and anaphora.
AB  - We investigated whether modal information elicited empirical effects with regard
      to discourse processing. That is, like tense information, one of the linguistic
      factors shown to be relevant in organizing a discourse representation is
      modality, where the mood of an utterance indicates whether or not it is asserted.
      Event-related potentials (ERPs) were used in order to address the question of the
      qualitative nature of discourse processing, as well as the time course of this
      process. This experiment investigated pronoun resolution in two-sentence
      discourses, where context sentences either contained a hypothetical or actual
      Noun Phrase antecedent. The other factor in this 2x2 experiment was type of
      continuation sentence, which included or excluded a modal auxiliary (e.g., must,
      should) and contained a pronoun. Intuitions suggest that hypothetical antecedents
      followed by pronouns asserted to exist present ungrammaticality, unlike actual
      antecedents followed by such pronouns. Results confirmed the grammatical
      intuition that the former discourse displays anomaly, unlike the latter (control)
      discourse. That is, at the Verb position in continuation sentences, we found
      frontal positivity, consistent with the family of P600 components, and not an
      N400 effect, which suggests that the anomalous target sentences caused a revision
      in discourse structure. Furthermore, sentences exhibiting modal information
      resulted in negative-going waveforms at other points in the continuation
      sentence, indicating that modality affects the overall structural complexity of
      discourse representation.

PMID- 16997289
TI  - Firing pattern and calbindin-D28k content of human epileptic granule cells.
AB  - In the hippocampus of chronic temporal lobe epilepsy, many abnormalities in
      structure and function have been described but their pathophysiological relevance
      often is poorly understood. In this study, we asked whether there may be a link
      between changes in the firing pattern and the loss of the calcium binding protein
      calbindin-D28k in epileptic hippocampal granule cells. Using the perforated patch
      clamp technique, we investigated granule cells in slices prepared from human
      hippocampi removed for the treatment of pharmacoresistant temporal lobe epilepsy.
      Granule cells in hippocampi without significant signs of structural damage
      (lesion group) displayed a firing pattern indistinguishable from that of rodent
      granule cells and were strongly labeled with anti-calbindin-D28k antibodies. In
      contrast, half of granule cells in sclerotic hippocampi (HS group) showed an
      altered firing pattern and a severe loss of calbindin-D28k. While these cells
      show passive membrane properties comparable to cells of the rodent and lesion
      group, they lack the medium afterhyperpolarization and display only a weak spike
      frequency adaptation. On the other hand, granule cells in the HS group have an
      increased action potential threshold and an enlarged fast afterhyperpolarization.
      Applying post-recording immunohistochemistry to individual electrophysiologically
      characterized granule cells, we show that the loss of calbindin-D28k is not
      causally related to any of the changes in firing pattern. Both alterations seem
      to occur during the course of temporal lobe epilepsy, with the firing pattern
      being affected earlier than the calbindin-D28k content. In conclusion, we propose
      that it is the combination of the altered intrinsic excitability of granule cells
      with the amplified and prolonged synaptic input from perforant path fibers
      previously described in the epileptic dentate area which promotes tonic, non
      adapting, high frequency firing of granule cells and thereby strongly augments
      the excitability of the hippocampus.

PMID- 16997290
TI  - Complete NMR characterization of lychnose from Stellaria media (L.) Vill.
AB  - Lychnose (alpha-D-Gal-(1-->6)-alpha-D-Glc-(1-->2)-beta-D-Fru-(1-->1)-alpha-D-Gal)
      was isolated from Stellaria media, a representative member of the Caryophyllaceae
      plant family. Weak acid hydrolysis, enzymatic hydrolysis and complete NMR
      characterization were performed to confirm the identity of the tetrasaccharide.
      All (1)H and (13)C resonances were unambiguously assigned and the conformation of
      the sugars was determined using one and two dimensional NMR techniques. Anomeric
      characterizations in lychnose were confirmed from HMBC and NOESY spectra.

PMID- 16997291
TI  - Structure of the O-polysaccharide of Escherichia coli O150 containing 2-acetamido
      4-O-[(S)-1-carboxyethyl]-2-deoxy-d-glucose.
AB  - An acidic O-polysaccharide was obtained by mild acid degradation of the
      lipopolysaccharide of Escherichia coli O150 and studied by sugar and methylation
      analyses, triflic acid solvolysis, Smith degradation, (1)H and (13)C NMR
      spectroscopy, including 2D ROESY, (1)H,(13)C HSQC, HMQC-TOCSY, and HMBC
      experiments. The polysaccharide was found to contain a regioisomer of N
      acetylisomuramic acid, 2-acetamido-4-O-[(S)-1-carboxyethyl]-2-deoxy-d-glucose [d
      GlcNAc4(Slac)]. The structure of its hexasaccharide repeating unit was
      established.

PMID- 16997292
TI  - Determination of carotid disease with the application of STFT and CWT methods.
AB  - In this study, Doppler signals were recorded from the output of carotid arteries
      of 40 subjects and transferred to a personal computer (PC) by using a 16-bit
      sound card. Doppler difference frequencies were recorded from each of the
      subjects, and then analyzed by using short-time Fourier transform (STFT) and the
      continuous wavelet transform (CWT) methods to obtain their sonograms. These
      sonograms were then used to determine the relationships of applied methods with
      medical conditions. The sonograms that were obtained by CWT method gave better
      results for spectral resolution than the STFT method. The sonograms of CWT method
      offer net envelope and better imaging, so that the measurement of blood flow and
      brain pressure can be made more accurately. Simultaneously, receiver operating
      characteristic (ROC) analysis has been conducted for this study and the
      estimation performance of the spectral resolution for the STFT and CTW has been
      obtained. The STFT has shown a 80.45% success for the spectral resolution while
      CTW has shown a 89.90% success.

PMID- 16997293
TI  - The C2H2 zinc finger genes of Strongylocentrotus purpuratus and their expression
      in embryonic development.
AB  - The C2H2 zinc finger is one of the most abundant protein domains and is thought
      to have been extensively replicated in diverse animal clades. Some well-studied
      proteins that contain this domain are transcriptional regulators. As part of an
      attempt to delineate all transcription factors encoded in the Strongylocentrotus
      purpuratus genome, we identified the C2H2 zinc finger genes indicated in the
      sequence, and examined their involvement in embryonic development. We found 377
      zinc finger genes in the sea urchin genome, about half the number found in mice
      or humans. Their expression was measured by quantitative PCR. Up to the end of
      gastrulation less than a third of these genes is expressed, and about 75% of the
      expressed genes are maternal; both parameters distinguish these from all other
      classes of regulatory genes as measured in other studies. Spatial expression
      pattern was determined by whole mount in situ hybridization for 43 genes
      transcribed at a sufficient level, and localized expression was observed in
      diverse embryonic tissues. These genes may execute important regulatory functions
      in development. However, the functional meaning of the majority of this large
      gene family remains undefined.

PMID- 16997294
TI  - Identification and developmental expression of the ets gene family in the sea
      urchin (Strongylocentrotus purpuratus).
AB  - A systematic search in the available scaffolds of the Strongylocentrotus
      purpuratus genome has revealed that this sea urchin has 11 members of the ets
      gene family. A phylogenetic analysis of these genes showed that almost all
      vertebrate ets subfamilies, with the exception of one, so far found only in
      mammals, are each represented by one orthologous sea urchin gene. The temporal
      and spatial expression of the identified ETS factors was also analyzed during
      embryogenesis. Five ets genes (Sp-Ets1/2, Sp-Tel, Sp-Pea, Sp-Ets4, Sp-Erf) are
      also maternally expressed. Three genes (Sp-Elk, Sp-Elf, Sp-Erf) are ubiquitously
      expressed during embryogenesis, while two others (Sp-Gabp, Sp-Pu.1) are not
      transcribed until late larval stages. Remarkably, five of the nine sea urchin ets
      genes expressed during embryogenesis are exclusively (Sp-Ets1/2, Sp-Erg, Sp-Ese)
      or additionally (Sp-Tel, Sp-Pea) expressed in mesenchyme cells and/or their
      progenitors. Functional analysis of Sp-Ets1/2 has previously demonstrated an
      essential role of this gene in the specification of the skeletogenic mesenchyme
      lineage. The dynamic, and in some cases overlapping and/or unique, developmental
      expression pattern of the latter five genes suggests a complex, non-redundant
      function for ETS factors in sea urchin mesenchyme formation and differentiation.

PMID- 16997295
TI  - Focus on molecules: aldose reductase.

PMID- 16997296
TI  - Protective effects of soft acrylic yellow filter against blue light-induced
      retinal damage in rats.
AB  - Recently, a yellow intraocular lens (IOL) was developed for the purpose of
      reducing potential blue light-induced retinal damage after cataract surgery.
      However, the effect of yellow filters on retinal protection remains to be
      clarified. To test the protective effects of yellow filters on blue light-induced
      retinal damage, a yellow and a clear soft acrylic filter were attached to the
      right and left eyes, respectively, of albino rats and exposed to 4.5 k lux blue
      fluorescent lights with peak wavelength at 420 nm (ranging 380-500 nm; short
      blue) or 446 nm (ranging 400-540 nm; long blue) for 6h. To assess retinal damage,
      the electroretinogram (ERG) was recorded at 7 days, outer nuclear layer (ONL)
      thickness and area were measured at 7 days, apoptosis was analyzed by TUNEL
      staining at 24 h, and the level of lipid peroxidation in retinas was assessed by
      Western dot blots using specific antibodies against 4-hydroxynonenal (4-HNE)- and
      carboxyethylpyrrole (CEP)-modified proteins immediately after light exposure.
      After short blue light exposure, a- and b-wave ERG amplitudes and the ONL
      thickness at 1-2.5 mm inferior and 0.5-2.5 mm superior to optic nerve head (ONH)
      were significantly reduced. TUNEL staining in the ONL at 0-2 mm inferior and 1-2
      mm superior to the ONH, and retinal levels of 4-HNE- and CEP-modified proteins
      were significantly increased in the clear filter-covered eyes compared to yellow
      filter-covered eyes. After long blue light exposure, the only difference seen was
      a greater ONL thickness at 1.5 mm superior to the ONH in yellow filter-covered
      eye. Transmission of light through the yellow filter was 58% for short blue and
      89% for long blue compared to the clear filter. The ONL area was not different
      between clear filter-covered and -uncovered eyes after exposure to short or long
      blue light. Given the results, yellow IOL material protects the retina against
      acute shorter wavelength blue light exposure more effectively than the clear IOL
      material.

PMID- 16997297
TI  - Lipopolysaccharide from Escherichia coli induces the expression of vascular
      endothelial growth factor via toll-like receptor 4 in human limbal fibroblasts.
AB  - Corneal neovascularization can be induced by a severe ocular infection, injury or
      immunological diseases. The vascular endothelial growth factor (VEGF) is the main
      cytokine involved in this phenomenon, inducing angiogenesis from the vascularized
      ocular tissues. As the limbal tissue is located between conjunctival and corneal
      tissues, we suggest that the limbal cells are participating in the production of
      VEGF induced by bacterial components as LPS. In this work, RT-PCRs and
      immunoblots were used to investigate the expression of VEGF and other pro
      angiogenic genes in primary cultures of human limbal fibroblasts (PCHLF) treated
      with lipopolysaccharide (LPS) from Escherichia coli. We found that the expression
      of VEGF was initiated at 6 h and reaches its highest expression at 72 h after
      stimulation with LPS. Up-regulation of toll-like receptor 4 (TLR4) after 3 h of
      treatment was also observed. LPS-induced the expression of VEGF in a dose
      dependent manner, and the blocking of TLR4 with an anti-TLR4 antibody prevented
      VEGF expression. We also analyzed the molecules that modulate VEGF expression.
      LPS did not induce the up-regulation of LL-37 nor the hypoxia induced factor 1
      alpha (HIF-1alpha) mRNA expression, however, an up-regulation of interleukin 13
      receptor alpha 1 (IL-13Ralpha1) and interleukin 4 receptor alpha (IL-4Ralpha)
      were observed after 3 and 12 h of stimulation, respectively. The expression of
      interleukin 13 did not change throughout the treatment. These results suggest
      that TLR4, IL-13Ralpha1 and IL-4Ralpha induced by LPS in PCHLF could be playing
      an important role in the corneal neovascularization.

PMID- 16997298
TI  - Differential protein distributions define two sub-compartments of the
      mitochondrial inner membrane in yeast.
AB  - The mitochondrial inner membrane exhibits a complex topology. Its infolds, the
      cristae membranes, are contiguous with the inner boundary membrane (IBM), which
      runs parallel to the outer membrane. Using live cells co-expressing functional
      fluorescent fusion proteins, we report on the distribution of inner membrane
      proteins in budding yeast. To this end we introduce the enlarged mitochondria of
      Deltamdm10, Deltamdm31, Deltamdm32, and Deltammm1 cells as a versatile model
      system to study sub-mitochondrial protein localizations. Proteins of the F(1)F(0)
      ATP synthase and of the respiratory chain complexes III and IV were visualized in
      the cristae-containing interior of the mitochondria. In contrast, proteins of the
      TIM23 complex and of the presequence translocase-associated motor were strongly
      enriched at the IBM. The different protein distributions shown here demonstrate
      that the cristae membranes and the IBM are functionally distinct sub
      compartments.

PMID- 16997299
TI  - Phosphorylation-dependent phospholipase D activity of matrix vesicles.
AB  - A progressive hydrolysis of phospholipids was observed during the mineralization
      process mediated by extracellular matrix vesicles. Increasing levels of different
      hydrolysis products revealed phospholipase A and D activities. The importance of
      these enzymes for the mineralization process lies in a high rate of hydrolysis of
      neutral phospholipids and lower rate of degradation of anionic phospholipids,
      which may favor mineral formation in vesicular membrane and membrane breakdown
      necessary for the release of mineral deposits into extracellular matrix. In this
      report, we focus on the phosphorylation-dependent phospholipase D activity during
      mineral formation initiated by chicken embryo matrix vesicles.

PMID- 16997300
TI  - Regulated upon activation, normal T cell expressed and secreted (RANTES) and
      monocyte chemotactic protein 1 in follicular fluid accumulate differentially in
      patients with and without endometriosis undergoing in vitro fertilization.
AB  - OBJECTIVE: To compare the amount of regulated upon activation, normal T cell
      expressed and secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1) in
      follicular fluid (FF) of patients with and without endometriosis and to determine
      their oocyte fertilization and pregnancy rates. DESIGN: Case-control study.
      SETTING: Department of Obstetrics and Gynecology, University Hospital Schleswig
      Holstein, Campus Luebeck, Germany. PATIENT(S): Thirty-two women with
      endometriosis stages I-IV and 28 women without endometriosis, both groups
      surgically and histologically confirmed. INTERVENTION(S): Diagnostic laparoscopy,
      IVF-ET. MAIN OUTCOME MEASURE(S): RANTES and MCP-1 levels in follicular fluid,
      measured by ELISA, and oocyte fertilization and pregnancy rates. RESULT(S):
      Follicular response and days of gonadotropin stimulation were similar between the
      two groups. The levels of RANTES in FF from patients with endometriosis were
      significantly higher (460.4 +/- 90.3 pg/mL) compared with concentrations in
      patients with tubal infertility (243.8 +/- 70.9 pg/mL; P<.05). In contrast, MCP-1
      concentrations in FF from women with endometriosis (330.0 +/- 29.2 pg/mL) were
      lower than in women with tubal infertility (420.5 +/- 46.6 pg/mL; P<.05). Oocyte
      fertilization rates in the endometriosis group (54%) were significantly lower
      than those of the tubal infertility group (73%; P<.05), as were the pregnancy
      rates (19% vs. 35%, respectively; P<.01). CONCLUSION(S): Women with endometriosis
      associated infertility have a poor IVF outcome. Immune cell recruitment into the
      ovary might affect follicular function and lead to impaired oocyte quality.

PMID- 16997301
TI  - Misoprostol alone vs. methotrexate followed by misoprostol for early abortion.

PMID- 16997302
TI  - The plasma kinetic open forceps for vascular hemostasis in vaginal hysterectomy.

PMID- 16997303
TI  - Volume of sampled amniotic fluid and prenatal cytogenetic diagnosis.

PMID- 16997304
TI  - Primary screening for cervical cancer through self sampling.
AB  - OBJECTIVE: To evaluate the use of community health agents (CHAs) to instruct
      women living in poor rural areas in obtaining self-collected cervical samples and
      compare the high-risk HPV (hrHPV) hybrid capture (HC) results obtained to those
      for gynecologist-collected samples. METHODS: After a one-day training, CHAs
      visited sexually active women, instructing each in the use of collection brush
      and the Universal Collection Medium tube. One week thereafter, a gynecologist
      collected cervical samples from, and performed colposcopies on, the same women. A
      single reference lab performed all HCs. RESULTS: 878 women (Age: 15-69 years)
      participated. Among self-collected samples, hrHPV prevalence was 33.9% (95% CI:
      30.8%-37%), compared with 28.6% (95% CI: 27%-30%) among gynecologist-collected
      samples. However, 9.3% of the patients were HPV HC II-positive in the self
      collected sample and HPV HC II-negative in the gynecologist-collected samples
      (95% CI: 7.38%-11.22%), whereas 4% tested positive in gynecologist-collected
      samples and negative in self-collected samples (95% CI: 2.7%-5.3%) (P<0.01;
      kappa=0.7). Of 9 cases of histologically-confirmed, high-grade squamous
      intraepithelial lesion, self-collected and provider-collected samples missed one
      each. CONCLUSION: Self-collected vaginal sampling could be made an additional CHA
      function under existing program conditions, improving access to cervical cancer
      screening in poor rural settings.

PMID- 16997305
TI  - Taiwanese nurses' attitudes towards and use of complementary and alternative
      medicine in nursing practice: a cross-sectional survey.
AB  - BACKGROUND: Increasingly, nurses in Western countries express positive attitudes
      to complementary and alternative medicine (CAM) but lack knowledge, access to
      education and organisational policy to guide practice. It is unclear whether
      nurses in developed Asian countries mirror or differ from this profile.
      OBJECTIVES: To determine the attitudes towards and use of CAM by registered
      nurses in Taiwan. DESIGN: Cross sectional survey. SETTING: A Nursing College in
      eastern Taiwan. PARTICIPANTS: Registered nurses (N=170) working in various
      clinical settings who were studying a post registration Bachelor of Nursing
      conversion course. METHODS: Questionnaire distributed to nurses during class
      time. RESULTS: Most nurses had positive attitudes to CAM and most used therapies,
      like massage, occasionally in practice. However, none had formal qualifications
      in CAM and most perceived that there were insufficient resources or
      organisational policy to facilitate practice. CONCLUSIONS: Taiwanese nurses need
      more formal education about CAM and require access to clear policies regarding
      the safe use of CAM in nursing practice.

PMID- 16997306
TI  - The association between a self-reported history of mental health problems and a
      history of parasuicide in a sample of UK male prisoners.
AB  - BACKGROUND: Prisoner parasuicide is a major public and mental health concern
      worldwide and within the United Kingdom. OBJECTIVES: This study used a cross
      sectional design to examine the association between a self-reported history of
      mental health problems and a history of parasuicide in male prisoners. METHODS: A
      total sample of 192 convicted prisoners who were about to be released from a
      local category "B" prison in the UK were approached and asked to complete the
      "Toolkit for Healthcare Needs Assessment in Prisons" which contained a range of
      demographic, mental and physical health questions. Unadjusted and adjusted odds
      ratios (with 95% confidence intervals) were determined using logistic regression.
      RESULTS: Fifty-one prisoners participated. The unadjusted odds ratio for having a
      self-reported history of mental health problems and a self-reported history of
      parasuicide was 15.6 (95% C.I., 2.96-82.16). Following adjustment for age, living
      alone, homelessness, illegal drug use and alcohol problems the odds ratio was
      11.32 (95% C.I., 1.80-71.13). DISCUSSION: This study provides good evidence of an
      association between a history of mental health problems and a history of
      parasuicide in a group of UK male prisoners.

PMID- 16997307
TI  - Superparamagnetic iron oxide binding and uptake as imaged by magnetic resonance
      is mediated by the integrin receptor Mac-1 (CD11b/CD18): implications on imaging
      of atherosclerotic plaques.
AB  - INTRODUCTION: Superparamagnetic iron oxide nanoparticles (SPIONs) have been
      successfully used for magnetic resonance imaging (MRI) of atherosclerotic
      plaques. Endocytosis into monocytes/macrophages has been proposed as the
      mechanism for SPION uptake, but a specific receptor has not been identified yet.
      A potential candidate is the versatile integrin Mac-1 (CD11b/CD18, alphaMbeta2),
      which is involved in leukocyte adhesion, complement activation and phagocytosis.
      METHODS AND RESULTS: Intracellular SPION-accumulation was confirmed in cultured
      human monocytes using immunohistochemistry and iron staining. Recombinant cells
      expressing Mac-1 in different activation states as well as human monocytes with
      or without PMA stimulation were incubated either with an unspecific IgG or a
      CD11b-blocking antibody. Thereafter, cells were incubated with FITC-labeled amino
      covered SPIONs or ferumoxtran-10 SPIONs and signal intensity was quantified by
      flow cytometry. Depending on the activation status of Mac-1, a significant
      increase in SPION binding/uptake was observed, independent on surface coating.
      Furthermore, SPION binding/uptake was significantly reduced after CD11b blockade.
      Results were confirmed in recombinant cells incubated with amino-PVA SPIONs and
      ferumoxtran-10, using T2(*)-weighted 3T MRI. CONCLUSION: The integrin Mac-1 is
      directly involved in SPION binding/uptake. Thus, monocytes abundantly expressing
      Mac-1 and especially activated monocytes expressing activated Mac-1 may be useful
      vehicles for high resolution MRI labeling of atherosclerotic plaques.

PMID- 16997309
TI  - Increase in circulating levels of adiponectin after treatment with statin and
      fibrate in patients with coronary artery disease and hyperlipidemia.

PMID- 16997308
TI  - Use and efficacy of abciximab in an unselected population with acute myocardial
      infarction treated with primary angioplasty: data from AMI-Florence registry.
AB  - AIMS: We sought to evaluate the determinants and the potential benefit of
      abciximab use in unselected patients with acute myocardial infarction treated
      with primary angioplasty. METHODS AND RESULTS: Based on the AMI-Florence
      registry, we analyzed 461 consecutive acute myocardial infarction patients
      treated with primary angioplasty, 280 (61%) of whom received abciximab. For each
      patient, a propensity score indicating the likelihood of abciximab treatment was
      calculated. Compared to those not treated, patients treated with abciximab were
      at lower risk. At multivariate analysis, the direct admission to a hospital with
      angioplasty facilities significantly increased the probability of receiving
      abciximab (OR 1.99, 95% CI 1.30-3.03, p=.001), while older age (OR 0.97, 95% CI
      0.95-0.98, p<.0001), non-anterior location (OR 0.58, 95% CI 0.38-0.88, p=.011)
      and Killip class >1 (OR 0.53, 95% CI 0.32-0.87, p=.013), were negative predictors
      of abciximab use. Primary angioplasty had a higher success rate in patients
      treated with abciximab (99.3% versus 96.5%, p=.03). In-hospital and 1-year
      mortality were significantly lower in patients treated with abciximab (2.5%
      versus 13.3%, p<.0001, and 7% versus 21%, p<.0001, respectively). At multivariate
      analysis patients treated with abciximab had a significantly lower risk of in
      hospital mortality (OR 0.35, 95% CI 0.14-0.93, p=.035), and a marginally lower
      risk of death at 1-year follow-up (HR 0.58, 95% CI 0.32-1.03, p=.065). These
      results did not change when the propensity score was included into the analyses.
      CONCLUSIONS: In the real practice, abciximab is more frequently used in patients
      at lower risk, particularly when directly admitted to a hospital with angioplasty
      facilities. Abciximab use is associated with a significant reduction in early
      mortality. A trend toward a reduced mortality is maintained also at 1 year.

PMID- 16997310
TI  - Reduced systemic inflammatory response to implantation of sirolimus-eluting
      stents in patients with stable coronary artery disease.
AB  - Stent implantation causes significant injury to the vascular wall, resulting in
      inflammatory activation. Although sirolimus-eluting stents (SES) have anti
      inflammatory properties, their effect on periprocedural systemic inflammatory
      response has not been sufficiently investigated. Eighty-one patients with stable
      coronary artery disease involving severe stenosis of one major epicardial
      coronary artery underwent coronary angioplasty with stent implantation and
      randomly received either SES or bare metal stents (BMS). Blood samples were taken
      24h before, at 24h, 48 h and 1 month after the angioplasty and levels of high
      sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-1 beta
      (IL-1 beta), and monocyte chemoattractant protein-1 (MCP-1) were determined.
      HsCRP after BMS implantation increased over 24h (p<0.001) and then remained
      steady, as did IL-6 and IL-1 beta similarly. In contrast, their levels in SES
      patients decreased to below baseline by the end of the month. MCP-1 levels
      increased by the end of 1 month (p<0.001) in the BMS group, whereas in SES they
      steadily decreased, becoming significantly lower than baseline from 48 h
      (p=0.015). In conclusion, patients with SES exhibit an attenuation of the
      postprocedural systemic inflammatory activation during a 1-month follow-up after
      stent implantation. This might partially explain the reduced restenosis rate
      associated with SES.

PMID- 16997311
TI  - Cyclic chronopotentiometric determination of sugars at Au and Pt microelectrodes
      in flowing solutions.
AB  - The main advantage of the application of cyclic chronopotentiometry (CCP) in end
      column CE detection arises from the fact that the detection parameters and the
      magnitude of the analytical signal are (in contrast with other electrochemical
      detection methods) independent of the ohmic polarization of the solution caused
      by the separation current at the detection end of the capillary. CCP was used to
      determine sugars on platinum and gold microelectrodes after separation by CE. The
      results obtained with a gold microelectrode were better. Subsequently this
      detection method was used for quantitative determination of sugars in honeys and
      for their authentication.

PMID- 16997312
TI  - Compliance analysis of phenylurea and related compounds in drinking water by
      liquid chromatography/electrospray ionization/mass spectrometry coupled with
      solid-phase extraction.
AB  - A liquid chromatography/electrospray ionization/mass spectrometry method was
      reported for the compliance analysis of seven phenylurea compounds and two
      related herbicides (tebuthiuron and propanil) in drinking water. The volumes of
      the sample and final extract used in the method were 500 mL and 10 mL,
      respectively. The obtained method detection limits were less than 0.03 microg/L,
      and the mean recoveries were 74-128% with a relative standard deviation of 2.6
      8.3% for all the studied compounds. The peak-to-peak signal-to-noise ratios
      ranged from 3.3 for cis-siduron to 34.2 for fluometuron. The accuracy and
      precision resulting from reagent and drinking water samples fortified at higher
      concentration levels were similar to these results. Several analytes were
      detected in the drinking water samples, including tebuthiuron at 0.5 microg/L,
      propanil at 0.7 microg/L, diuron at 0.1-2.1 microg/L, and linuron at 0.1-0.8
      microg/L.

PMID- 16997313
TI  - Nano-structured lead dioxide as a novel stationary phase for solid-phase
      microextraction.
AB  - The first study on the high efficiency of nano-structured lead dioxide as a new
      fiber for solid-phase microextraction (SPME) purposes has been reported. The size
      of the PbO2 particles was in the range of 34-136 nm. Lead dioxide-based fibers
      were prepared via electrochemical deposition on a platinum wire. The extraction
      properties of the fiber to benzene, toluene, ethylbenzene, and xylenes (BTEX)
      were examined using headspace solid-phase microextraction (HS-SPME) mode coupled
      to gas chromatography-flame ionization detection (GC-FID). The results obtained
      proved the suitability of proposed fibers for the sampling of organic compounds
      from water. The extraction procedure was optimized by selecting the appropriate
      extraction parameters, including preparation conditions of coating, salt
      concentration, time and temperature of adsorption and desorption and stirring
      rate. The calibration graphs were linear in a concentration range of 0.1-100
      microg l(-1) (R2 > 0.994) with detection limits below 0.012 microg l(-1) level.
      Single fiber repeatability and fiber-to-fiber reproducibility were less than 10.0
      and 12.5%, respectively. The PbO2 coating was proved to be very stable at
      relatively high temperatures (up to 300 degrees C) with a high extraction
      capacity and long lifespan (more than 50 times). Higher chemical resistance and
      lower cost are among the advantages of PbO2 fibers over commercially available
      SPME fibers. Good recoveries (81-108%) were obtained when environmental samples
      were analyzed.

PMID- 16997314
TI  - Isolation and quantification of oligomeric pyranoanthocyanin-flavanol pigments
      from red wines by combination of column chromatographic techniques.
AB  - A combination of column chromatography on Toyopearl gel HW-40 (S) and polyamide
      resin has been developed for the preparative isolation and further determination
      of pyranoanthocyanins of oligomeric nature formed after reaction between
      anthocyanins and different flavanols in a complex wine matrix. Polyamide
      chromatography was found to be exceptionally useful to separate oligomeric
      pyanoanthocyanins from other classes of wine flavonoids and polymerized pigments
      into an advanced state of purity for further identification and quantification by
      HPLC-diode array detector coupled with electrospray ionization mass spectrometry
      (HPLC-DAD/ESI-MS). Fractionation on Toyopearl gel chromatography allowed the
      separation of pyranoanthocyanins bearing the same flavanols (catechin,
      epicatechin and procyanidin dimers) but with different anthocyanin moieties
      (either acylated or non-acylated in the glucose residue) in order to allow
      further isolation of individual oligomeric pigments on C18 chromatography. A
      quantitative procedure for analyzing the major pyranoanthocyanin-flavanol
      derivatives in different aged wines is proposed for the first time. Results
      obtained showed good reproducibility and recovery regarding sample pretreatment
      and quantitative method for all analyzed oligomeric pyranoanthocyanins. The
      combination of these two chromatographic separations is likely to be applicable
      to the preparative isolation of other anthocyanin-derived pigments.

PMID- 16997315
TI  - Versatile transmission ellipsometry to study linear ferrofluid magneto-optics.
AB  - Linear birefringence and dichroism of magnetite ferrofluids are studied
      simultaneously using spectroscopic ellipsometry in transmission mode. It is shown
      that this versatile technique enables highly accurate characterisation of magneto
      optical phenomena. Magnetic field-dependent linear birefringence and dichroism as
      well as the spectral dependence are shown to be in line with previous results.
      Despite the qualitative agreement with established models for magneto-optical
      phenomena, these fail to provide an accurate, quantitative description of our
      experimental results using the bulk dielectric function of magnetite. We discuss
      the results in relation to these models, and indicate how the modified dielectric
      function of the magnetite nanoparticles can be obtained.

PMID- 16997316
TI  - Mesopore control of high surface area NaOH-activated carbon.
AB  - Activated carbon with BET surface areas in a narrow range from 2318 to 2474 m2/g
      was made by soaking the char made from corncob in a concentrated NaOH solution at
      NaOH/char ratios from 3 to 6; the mesopore volumes of the activated carbon were
      significantly changed from 21 to 58%. The relationships between pore properties
      (Sp, Vpore, Vmicro/Vpore, Dp) and NaOH dosage were investigated. Comparisons
      between the methods of NaOH and KOH activation revealed that NaOH activation can
      suitably control the mesopore specific volume of the activated carbon. Elemental
      analysis revealed that the H/C and O/C values of the activated carbons of
      NaOH/char ratios from 3 to 6 were significantly lower. SEM observation of surface
      hole variation of the activated carbon ascertained that the reaction process was
      inner pore etching. Based on the above three measurements and experimental
      investigations, the assumption made by previous researchers, namely that NaOH and
      KOH produce similar results, was challenged. Furthermore, the adsorption kinetics
      was used to investigate the adsorption rate of an Elovich equation to determine
      the relationships between the adsorption behavior on larger molecules (dyes) and
      smaller molecules (phenols) and the pore structure of the activated carbon.

PMID- 16997317
TI  - Forced expression of AID facilitates the isolation of class switch variants from
      hybridoma cells.
AB  - Monoclonal antibodies are used in the treatment and diagnosis of diseases and to
      study the protective and adverse functions of antibodies in vitro and in vivo.
      Since the isotype determines the effector function, half-life in the serum and
      distribution throughout the body, it would be useful to have a battery of
      antibodies with the same binding site associated with different isotypes.
      However, since hybridomas switch isotypes at very low frequencies in tissue
      culture, it has been difficult and very labor intensive to isolate panels of
      class switch variants. We show here that stable transfection of activation
      induced cytidine deaminase (AID) in hybridomas increased their frequency of
      switching to a level that greatly facilitated the isolation of subclones
      expressing monoclonal antibodies of different isotypes. Although forced
      expression of AID also increased the frequency of somatic hypermutation in the
      immunoglobulin variable regions that encode the antigen binding site, antigen
      recognition was retained in the isotype switched antibodies.

PMID- 16997318
TI  - Effective evaluation of novel low-cost CD4 monitoring assays.
AB  - Indian generic pharmaceutical manufacturers have dramatically reduced the price
      of antiretroviral therapy thus improving access, but monitoring costs of the
      patients on therapy remain high. Few low-cost monitoring assays are available and
      validation against gold standard is exceedingly important before implementation.
      Validity is defined as the degree to which the results of the new technique
      correspond to the true state of the phenomena being measured by the gold
      standard. Majority of publications report validation of low-cost CD4 assay using
      correlation coefficient, which is the best measure of association, and a few
      publications report intra-class correlation coefficient, which is a measure of
      reliability. However, Bland-Altman analysis that directly quantifies the
      difference seen between the novel low-cost CD4 assay and the gold standard is the
      most ideal approach. Absolute CD4 counts estimated for samples collected from 110
      HIV+ and 118 HIV- individuals using novel EasyCD4 assay and the gold standard
      FACSCount assay were validated using correlation coefficient, intra-class
      correlation coefficient and Bland Altman analysis. The results from these
      different analyses have been compared and the significance of each has been
      explained. Hence, to validate a low-cost assay Bland-Altman analysis and plot is
      recommended.

PMID- 16997319
TI  - Oleic acid is elevated in cell membranes during rapid cold-hardening and pupal
      diapause in the flesh fly, Sarcophaga crassipalpis.
AB  - The integrity of cellular membranes is critical to the survival of insects at low
      temperatures, thus an advantage is conferred to insects that can adjust their
      composition of membrane fatty acids (FAs). Such changes contribute to
      homeoviscous adaption, a process that allows cellular membranes to maintain a
      liquid-crystalline state at temperatures that are potentially low enough to cause
      the membrane to enter the gel state and thereby lose its ability to maintain
      homeostasis. Flesh flies (Sarcophaga crassipalpis) were subjected to two
      experimental conditions that elicit low temperature tolerance: rapid cold
      hardening and diapause. FAs were isolated and analyzed using gas chromatography
      mass spectrometry. FAs changed in response to both rapid cold-hardening and
      diapause. In response to rapid cold-hardening (8 h at 4 degrees C), the
      proportion of oleic acid (18:1n-9) in pharate adults increased from 30% to 47% of
      the total FA pool. The proportion of almost every other FA was reduced. By
      entering diapause, pupae experienced an even greater increase in oleic acid
      proportion, to 58% of the total FA pool. Oleic acid not only promotes membrane
      fluidity at low temperature but also allows the cell membrane to maintain a
      liquid crystalline state if temperatures increase.

PMID- 16997320
TI  - Phase-related body-color polyphenism in hatchlings of the desert locust,
      Schistocerca gregaria: re-examination of the maternal and crowding effects.
AB  - The mechanism controlling the body color of hatchlings was studied for the desert
      locust, Schistocerca gregaria. A pheromonal factor secreted by gregarious female
      adults into the foam plugs of egg pods has been suggested to cause darkening in
      their progeny. We re-examined the role of this maternal factor by washing or
      separating eggs at deposition. Eggs produced by crowd-reared female adults were
      washed with saline or separated individually without being washed immediately
      after deposition and the body color of the hatchlings from them was compared with
      that from the eggs unwashed and kept in the egg pod until hatching. Most
      hatchlings were dark and no significant difference was found in the proportions
      of dark- and light-colored hatchlings between the treatments and controls.
      Likewise, eggs separated before the foam plug deposition produced dark-colored
      hatchlings as in the un-separated controls. These results demonstrated that
      neither washing nor separation of eggs at deposition affected the hatchling body
      coloration. The variation in hatchling body color was correlated closely to the
      body weight at hatching, indicating that hatchling body color had been determined
      maternally. Green hatchlings reared under crowded conditions remained green until
      the second stadium at which black patterns were induced. It was concluded that
      body color at hatching has been determined maternally and crowding during the
      first nymphal stadium influences nymphal body color but its effect is not
      manifested until the second stadium. The present study casts doubts on the
      presence of a recently suggested pheromonal factor on the color of the
      hatchlings.

PMID- 16997321
TI  - Investigating saccade programming in the praying mantis Tenodera aridifolia using
      distracter interference paradigms.
AB  - To investigate the saccadic system in the mantis, I applied distracter
      interference paradigms. These involved presenting the mantis with a fixation
      target and one or several distracters supposed to affect saccades towards the
      target. When a single target was presented, a medium-sized target located in its
      lower visual field elicited higher rates of saccade response. This preference for
      target size and position was also observed when a target and a distracter were
      presented simultaneously. That is, the mantis chose and fixated the target rather
      than a distracter that was much smaller or larger than the target, or was located
      above the target. Furthermore, the mantis' preference was not affected by
      increasing the number of distracters. However, the presence of the distracter
      decreased the occurrence rate of saccade and increased the response time to
      saccade. I conclude that distracter interference paradigms are an effective way
      of investigating the visual processing underlying saccade generation in the
      mantis. Possible mechanisms of saccade generation in the mantis are discussed.

PMID- 16997322
TI  - Rapid kinetics of protein-nucleic acid interaction is a major component of HIV-1
      nucleocapsid protein's nucleic acid chaperone function.
AB  - The nucleic acid chaperone activity of the human immunodeficiency virus type-1
      (HIV-1) nucleocapsid protein (NC) plays an important role in the retroviral life
      cycle, in part, by facilitating numerous nucleic acid rearrangements throughout
      the reverse transcription process. Recent studies have identified duplex
      destabilization and nucleic acid aggregation as the two major components of NC's
      chaperone activity. In order to better understand the contribution of the
      functional domains of NC to these two activities, we used optical tweezers to
      stretch single lambda DNA molecules through the helix-coil transition in the
      presence of wild-type or mutant HIV-1 NC. Protein-induced duplex destabilization
      was measured directly as an average decrease of the force-induced melting free
      energy, while NC's ability to facilitate strand annealing was determined by the
      amount of hysteresis in the DNA stretch-relax cycle. By studying zinc-free
      variants of full-length and truncated NC, the relative contributions of NC's zinc
      fingers and N-terminal basic domain to the two major components of chaperone
      activity were elucidated. In addition, examination of NC variants containing
      mutations affecting one or both zinc finger motifs showed that effective strand
      annealing activity is correlated with NC's ability to rapidly bind and dissociate
      from nucleic acids. NC variants with slow on/off rates are inefficient in strand
      annealing, even though they may still be capable of high affinity nucleic acid
      binding, duplex destabilization, and/or nucleic acid aggregation. Taken together,
      these observations establish the rapid kinetics of protein-nucleic acid
      interaction as another major component of NC's chaperone function.

PMID- 16997323
TI  - Iron incorporation in Streptococcus suis Dps-like peroxide resistance protein Dpr
      requires mobility in the ferroxidase center and leads to the formation of a
      ferrihydrite-like core.
AB  - The Dps-like peroxide resistance protein (Dpr) is a dodecameric protein that
      protects the human and swine pathogen Streptococcus suis from hydrogen peroxide
      by removing free Fe2+ from the cytosol. Subsequent oxidation of iron by Dpr
      results in the deposition of Fe3+ inside the protein's central cavity. Structural
      changes that occur in the ferroxidase center were studied by X-ray
      crystallography after soaking Dpr crystals with Fe2+ in the presence of sodium
      dithionite. Twelve iron-binding sites were identified with each site formed by
      residues Asp74 and Glu78 from one subunit, and Asp63, His47 and His59 from a 2
      fold symmetry-related subunit. Compared to the iron-free Dpr, Asp74 and Glu78
      were found to be the most flexible amino acid residues and able to adopt a
      variety of conformations in different subunits. The crystal structure of an
      Asp74Ala Dpr mutant soaked with a Fe2+ -solution revealed variations in the Asp63
      position and no iron bound to the ferroxidase center. These results indicate an
      intrinsic flexibility in the active site that may be important for the catalytic
      reaction and subsequent nucleation events. Two iron cores with remarkably
      different features were identified in Dpr using X-ray absorption spectroscopy.
      Purified Dpr was found to have a small-size iron core with only approximately 16
      iron atoms/dodecamer forming a ferritin-like ferrihydrite structure. Because of
      its size, this core represents the smallest iron core identified so far in
      ferritins and other Dps-like proteins. A large-size core (approximately 180 iron
      atoms/dodecamer) formed after incubating the protein with a ferrous solution
      shows differences in iron coordination compared to the small size core.
      Characterization of the two iron cores in Dpr could provide insights into
      nucleation events and the mechanism of iron core growth in the Dps family of
      proteins.

PMID- 16997324
TI  - blm3-1 is an allele of UBP3, a ubiquitin protease that appears to act during
      transcription of damaged DNA.
AB  - Yeast Blm10 and mammalian PA200 proteins share significant sequence similarity
      and both cap the ends of 20 S proteasomes and enhance degradation of some peptide
      substrates. Blm10 was identified as a suppressor of the yeast blm3-1 mutation,
      and initially was thought to be the Blm3 protein. Both the blm3-1 and blm10-Delta
      mutations were reported to cause sensitivity to bleomycin and other forms of DNA
      damage, suggesting a role for Blm10/PA200-proteasome complexes in DNA repair. We
      have been unable to observe significant DNA damage sensitivity in blm10-Delta
      mutants in several genetic backgrounds, and we have therefore further
      investigated the relationship between BLM10 and blm3-1. We find that blm3-1 is a
      nonsense mutation in the ubiquitin protease gene UBP3. Deleting UBP3 causes
      phenotypes similar to those caused by blm3-1, but neither causes a general defect
      in DNA repair. Ubp3 has several known functions, and genetic interaction data
      presented here suggest an additional role in transcriptional elongation. The
      phenotypes caused by blm3-1 and ubp3-Delta mutations are not suppressed by over
      expression of BLM10, nor are they affected by deletion of BLM10. These results
      remove key components of the previously reported connection between Blm10/PA200
      proteasome complexes and DNA repair, and they suggest a novel way to interpret
      sensitivity to bleomycin as resulting from defects in transcription elongation.

PMID- 16997325
TI  - Evidence that creation of invasion sites determines the rate of strand transfer
      mediated by HIV-1 reverse transcriptase.
AB  - Strand transfer during reverse transcription can produce genetic recombination in
      human immunodeficiency virus type 1 (HIV-1) when two genomic RNAs, that are not
      identical, are co-packaged in the virus. Strand transfer was measured in vitro,
      in reactions involving primer switching from a donor to acceptor RNA template.
      The transfer product appeared with much slower kinetics than full-length
      synthesis on the donor template. The goal of this study was to learn more about
      the transfer mechanism by defining the steps that limit its rate. We previously
      proposed transfer to include the steps of acceptor invasion, hybrid propagation,
      terminus transfer, and re-initiation of synthesis on the acceptor template.
      Unexpectedly, with our templates increasing acceptor concentration increased the
      transfer efficiency but had no effect on the rate of transfer. Templates with a
      short region of homology limiting hybrid propagation exhibited a slow
      accumulation of transfer products, suggesting that for tested long homology
      templates hybrid propagation was not rate limiting. Substituting a DNA acceptor
      and adding Klenow polymerase accelerated re-initiation and extension exclusively
      on the DNA acceptor. This lead to a small rate increase due to faster extension
      on the acceptor, suggesting re-initiation of synthesis on the tested RNA
      acceptors was not rate limiting. A substrate was designed in which the 5' end of
      the primer was single stranded, and complimentary to the acceptor, i.e. having a
      pre-made invasion site. With this substrate, increasing concentrations of
      acceptor increased the rate of transfer. Together these data suggest that RNase H
      cleavage, and dissociation of RNA fragments creating an invasion site was rate
      limiting on most tested templates. When an accessible invasion site was present,
      acceptor interaction at that site influence the rate.

PMID- 16997326
TI  - Ameboid cell motility: a model and inverse problem, with an application to live
      cell imaging data.
AB  - In this article a mathematical model for ameboid cell movement is developed using
      a spring-dashpot system with Newtonian dynamics. The model is based on the facts
      that the cytoskeleton plays a primary role for cell motility and that the
      cytoplasm is viscoelastic. Based on the model, the inverse problem can be posed:
      if a structure like a spring-dashpot system is embedded into the living cell,
      what kind of characteristic properties must the structure have in order to
      reproduce a given movement of the cell? This inverse problem is the primary topic
      of this paper. On one side the model mimics some features of the movement, and on
      the other side, the solution to the inverse problem provides model parameters
      that give some insight, principally into the mechanical aspect, but also, through
      qualitative reasoning, into chemical and biophysical aspects of the cell.
      Moreover, this analysis can be done locally or globally and in different media by
      using the simplest possible information: positions of the cell and nuclear
      membranes. It is shown that the model and solution to the inverse problem for
      simulated data sets are highly accurate. An application to a set of live cell
      imaging data obtained from random movements of a human brain tumor cell (U87-MG
      human glioblastoma cell line) then provides an example of the efficiency of the
      model, through the solution of its inverse problem, as a way of understanding
      experimental data.

PMID- 16997327
TI  - Total and opportunistic algal cover in relation to environmental variables.
AB  - Based on a large data set from the national Danish monitoring program, spatial
      and temporal variability in total algal cover and in the fraction of
      opportunistic macroalgae was analysed in relation to environmental variables.
      Variations in water clarity and salinity combined with information on
      geographical location of sampling areas were found to explain almost 80% of the
      large-scale variation in algal cover between areas. As water clarity was largely
      regulated by concentrations of total-nitrogen (TN), and TN-concentrations by TN
      input from land, total algal cover at given water depths was partly related to TN
      input from land. The fraction of opportunistic algae responded predominantly to
      differences in salinity, the highest fractions being found in the most brackish
      areas. Temporal variability in algal cover and fraction of opportunists over the
      14-year investigation period was much smaller than the variability between areas
      and could not be predicted from variations in environmental variables. In order
      for macroalgal cover to become a more sensitive indicator of water quality it
      would be necessary to either increase the sensitivity of the method or identify
      and include supplementary regulating factors in the model.

PMID- 16997328
TI  - Statistical principles for ecological status classification of Water Framework
      Directive monitoring data.
AB  - Bias, precision and confidence of the classification framework are crucial
      elements for decisions to invest large sums to improve the ecological quality. In
      this study, the statistical principles for classification in relation to WFD are
      outlined and exemplified. Indicator adjustment to seasonal variation and other
      significant covariates reduces bias and improves precision. Precision is
      generally improved using annual means with seasonal adjustment instead of
      seasonal means. For classification I argue that the balance between costs of
      monitoring and reduction measures is only fully maintained by the fail-safe
      approach. The required monitoring efforts to ensure a precise classification are
      substantially higher than envisaged in WFD, for nutrients and phytoplankton
      measurements as high as 500 observations to characterise a water body. It must be
      ensured that sufficient monitoring data become available for classification,
      while indicator bias and precision is improved through modelling and further
      development of measurement techniques.

PMID- 16997329
TI  - Biological effects in the management of chemicals in the marine environment.
AB  - Coastal ecosystems are impacted by many stressors, of which chemicals are
      possibly not the most important. Chemicals differ from most other stressors such
      as eutrophication and hypersedimentation in the time scale-effects from the
      latter act on the scale of weeks or months, whereas effects from chemicals may
      take years to manifest themselves in population or community changes. There are
      four different approaches available to manage chemicals in marine ecosystems:
      target contaminant levels, target individual effects, target community impacts
      (biodiversity) and, finally, target processes. These four differ in the
      analytical methods available and the analyst's ability to separate effects from
      chemicals from other environmental factors and natural variation. There is
      furthermore, a need to develop a framework to integrate biological effects
      methods with risk assessment methodology. Such integration will improve the basis
      for risk-based assessment of chemicals. A problematic issue relevant to all
      aspects of environmental management are the interactions between chemicals, and
      between chemicals and eutrophication or sedimentation. There is a clear need for
      more knowledge about such interactions.

PMID- 16997330
TI  - Influence of DNA repair gene polymorphisms of hOGG1, XRCC1, XRCC3, ERCC2 and the
      folate metabolism gene MTHFR on chromosomal aberration frequencies.
AB  - We have studied the effect of genetic polymorphisms in the DNA repair genes
      hOGG1, XRCC1, XRCC3, ERCC2 and the MTHFR gene in the folate metabolism on the
      frequencies of cells with chromosomal aberrations (CA), chromosome-type
      aberrations (CSA), chromatid-type aberrations (CTA), chromatid breaks (CTB) and
      chromatid gaps (CTG) scored in peripheral blood lymphocytes from 651 Norwegian
      subjects of Caucasian descendant. DNA was extracted from fixed cell suspensions.
      The log-linear Poisson regression model was used for the combined data which
      included age, smoking, occupational exposure and genotype for 449 subjects. Our
      results suggest that individuals carrying the hOGG1 326Cys or the XRCC1 399Gln
      allele have an increased risk of chromosomal damage, while individuals carrying
      the XRCC1 194Trp or the ERCC2 751Gln allele have a reduced risk regardless of
      smoking habits and age. Individuals carrying the XRCC1 280His allele had an
      increased risk of CSA which was only apparent in non-smokers. This was
      independent of age. A protective effect of the XRCC3 241Met allele was only found
      in the older age group in non-smokers for CA, CSA and CTA, and in smokers for
      CSA. In the youngest age group, the opposite effect was found, with an increased
      risk for CA, CTA and CTG in smokers. Carrying the MTHFR 222Val allele gave an
      increased risk for chromosome and chromatid-type aberrations for both non-smokers
      and smokers, especially for individuals in the older age group, and with variable
      results in the youngest age group. The variables included in the different
      regression models accounted, however, for only 4-10% of the variation. The
      frequency ratio for CTG was significantly higher than for CTA and CTB for only 7
      of the 43 comparisons performed. Some of the gap frequencies diverge from the
      trend in the CA, CSA, CTA and CTB results.

PMID- 16997331
TI  - Embryonic stem cells deficient for Brca2 or Blm exhibit divergent genotoxic
      profiles that support opposing activities during homologous recombination.
AB  - The breast cancer susceptibility protein, Brca2 and the RecQ helicase, Blm (Bloom
      syndrome mutated) are tumor suppressors that maintain genome integrity, at least
      in part, through homologous recombination (HR). Brca2 facilitates HR by
      interacting with Rad51 in multiple regions, the BRC motifs encoded by exon 11 and
      a single domain encoded by exon 27; however, the exact importance of these
      regions is not fully understood. Blm also interacts with Rad51 and appears to
      suppress HR in most circumstances; however, its yeast homologue Sgs1 facilitates
      HR in response to some genotoxins. To better understand the biological importance
      of these two proteins, we performed a genotoxic screen on mouse embryonic stem
      (ES) cells impaired for either Brca2 or Blm to establish their genotoxic profiles
      (a cellular dose-response to a wide range of agents). This is the first side-by
      side comparison of these two proteins in an identical genetic background. We
      compared cells deleted for Brca2 exon 27 to cells reduced for Blm expression and
      find that the Brca2- and Blm-impaired cells exhibit genotoxic profiles that
      reflect opposing activities during HR. Cells deleted for Brca2 exon 27 are
      hypersensitive to gamma-radiation, streptonigrin, mitomycin C and camptothecin
      and mildly resistant to ICRF-193 which is similar to HR defective cells null for
      Rad54. By contrast, Blm-impaired cells are hypersensitive to ICRF-193, mildly
      resistant to camptothecin and mitomycin C and more strongly resistant to
      hydroxyurea. These divergent profiles support the notion that Brca2 and Blm
      perform opposing functions during HR in mouse ES cells.

PMID- 16997332
TI  - A dedicated neural mechanism for vowel selection: a case of relative vowel
      deficit sparing the number lexicon.
AB  - We report the case of an Italian speaker (GBC), with classical Wernicke's aphasia
      following a vascular lesion in the posterior middle temporal region. GBC
      exhibited a selective deficit in spoken language production affecting vowels more
      than consonants. In reading from a newspaper, GBC substituted vowels for other
      vowels from the Italian inventory at a rate of 7/1 compared to consonants. No
      effects of frequency or grammatical class were found. Vowel errors could also not
      be accounted for by morphological or known phonological processes. Production of
      number words, in contrast, was free from phonological errors. While GBC has
      intact representations of Italian vowels and consonants, his data argue for a
      separate selection mechanism for vowels that is dissociable from that used for
      consonants. This case provides neuropsychological evidence for models of word
      production that distinguish between the abstract phonological properties of a
      word (e.g., sequencing of phonemic slots, or "CV skeleton") and a separate
      representation for the specific sounds (melody).

PMID- 16997333
TI  - Neural correlates of arithmetic and language comprehension: a common substrate?
AB  - There is debate as to the relationship between mathematical ability and language.
      Some research has suggested that common processes underlie arithmetic and grammar
      while other research has suggested that these are distinct processes. The current
      study aimed to address this issue in a large group of 68 left hemisphere stroke
      patients who were all tested on analogous arithmetic and language comprehension
      measures. The behavioral data revealed a significant correlation between
      performance on the comprehension and arithmetic measures, although a subset of
      patients showed a dissociation in performance on the two tasks. To determine the
      brain regions critical for performance on each measure, patients' lesions were
      analyzed using Voxel-based Lesion Symptom Mapping. Arithmetic was associated with
      a small number of foci, with the most significant region located in the left
      inferior parietal lobule (Brodmann areas 39 and 40). Comprehension was associated
      with a larger number of brain regions, most extensively in the left middle and
      superior temporal gyri. There was also overlap between the arithmetic and
      comprehension maps in a number of regions, such as the inferior frontal gyrus.
      Our findings suggest that arithmetic and language comprehension are mediated by
      partially overlapping brain networks. These findings are discussed in light of
      previous work on the neural basis of arithmetic ability and its relationship to
      language.

PMID- 16997334
TI  - Odor-facilitated reentrainment in male and female juvenile Octodon degus.
AB  - The social, diurnal rodent, Octodon degus, exhibits faster reentrainment rates of
      circadian activity when exposed to olfactory social cues from females already
      entrained to the new light cycle (donors) during reentrainment after a phase
      shift of the light:dark (LD) cycle. However, adult degus display sex differences
      in the use of olfactory stimuli to accelerate reentrainment, with intact males
      requiring odors from at least two females for accelerated reentrainment, while
      odors from a single female are sufficient for faster recovery for females. In
      addition, adult gonadal hormones modulate responsiveness to the rate-enhancing
      olfactory stimuli. The present study examines responsiveness to reentrainment
      accelerating odors in juvenile animals just prior to puberty. We report that the
      sex difference in sensitivity observed in adults is not evident in juveniles;
      both males and females, when exposed to odors from one unfamiliar adult,
      accelerated reentrainment of circadian activity after a 6-h phase-advance of the
      LD cycle. In conjunction with adult data, these results suggest that the
      sensitivity-reducing role of testosterone does not change across the life span,
      while the sensitivity-enhancing role of ovarian hormones in females occurs only
      post-pubertally.

PMID- 16997335
TI  - Very-long-chain secondary alcohols and alkanediols in cuticular waxes of Pisum
      sativum leaves.
AB  - In cuticular waxes from leaves of Pisum sativum, 19 secondary alcohols, 10
      primary/secondary alkanediols and three secondary/secondary alkanediols were
      identified by various chemical transformations with product assignment employing
      GC-MS. The homologous series of C29-C33 secondary alcohols (1.1 microg/cm2) was
      dominated by hentriacontanol isomers (94%). Only octacosanediols and trace
      amounts of hexacosanediols (< 1%) were detected in the primary/secondary
      alkanediol faction (0.7 microg/cm2). The secondary/secondary alkanediols (0.12
      microg/cm2) contained a single homologue with chain length C31. All three
      compound classes showed characteristic isomer distributions with secondary
      functional groups predominantly located between C-14 and C-16. Based on the
      isomer compositions, the sequence of biosynthetic steps introducing the hydroxyl
      functions is discussed.

PMID- 16997336
TI  - Primary culture of fibroblasts and cementoblasts of the equine periodontium.
AB  - Fibroblasts and cementoblasts in the periodontal ligament (PDL) of equine cheek
      teeth were harvested, and monocultures were obtained by means of a "selective
      detachment" procedure. Cells were characterized by morphological criteria and by
      immunostaining for vimentin, FVIII, pan-cytokeratin, smooth muscle actin, and pro
      collagen. Cementogenic potential of the cells was determined by immunostaining
      for osteopontin and by histochemical detection of alkaline phosphatase. Equine
      periodontal fibroblasts (EPF) were spindle-shaped and polygonal. Equine dental
      cementoblasts (EDC) grew in cobblestone-like clusters. Both EPF and EDC stained
      positive for vimentin. Only EPF contained smooth muscle actin, pro-collagen, and
      alkaline phosphatase. Few EDC stained positive for osteopontin. The phenotypes of
      EPF and EDC and their specific expression of proteins corresponded to PDL
      fibroblasts and dental cementoblasts of other species. These results indicate the
      potential use of EPF and EDC in an adequate in vitro model of equine
      cementogenesis and equine periodontal remodeling.

PMID- 16997337
TI  - Experimental coccidiosis provoked by Eimeria acervulina in chicks simultaneously
      fed on ochratoxin A contaminated diet.
AB  - The progression of coccidiosis provoked by Eimeria acervulina was followed in
      chicks fed on OTA-contaminated as well as on OTA-free diets. More heavy progress
      of duodenal coccidiosis, including mortality, occurred in OTA-treated chicks as
      can be seen from the higher value of lesion (3.50) and oocyst (31.65) indices. A
      stronger decrease of serum total protein was found in OTA-treated chicks (22.80
      g/l) than in chicks infected with E. acervulina(24.20 g/l), but that decrease was
      strongest in chicks treated with OTA and simultaneously infected with E.
      acervulina (19.71 g/l). The serum concentration of uric acid was significantly
      increased in all chicks exposed to OTA, most notably in those additionally
      infected with E. acervulina (1020.6 (micro mol/L), whereas the serum enzyme
      activity of AST was increased only in chicks infected with E. acervulina and
      highest in those fed OTA contaminated diet (122.2 U/L). OTA induced degenerative
      changes in kidneys, liver and heart as well as a depletion of lymphoid tissue in
      the lymphoid organs and a decrease of body weight. Coccidiosis induced only a
      slight growth depression and duodenal hemorrhages in addition to characteristic
      duodenal damages. The impairment of kidney function, histopathological changes
      and general growth depression were stronger when chicks infected with E.
      acervulina were also given OTA.

PMID- 16997338
TI  - Comparison of tuberculin skin test response after three modalities of neonatal
      BCG vaccination.
AB  - The aim of this study was to determine the tuberculin skin test (TST) response to
      three different BCG modalities [0.1 ml Tokyo (n=104), 0.05 ml Pasteur-Merieux
      (n=137) and 0.1 ml Pasteur-Merieux (n=100)] in a cohort of healthy newborns 5
      months after vaccination at birth in Santiago, Chile. Among the 341 infants,
      91.2% had a response to TST, and the mean+/-SD TST reaction size was
      significantly larger in infants receiving the Tokyo strain than in those
      receiving the 0.05 ml or 0.1 ml Pasteur-Merieux strains (4.4+/-2.0, 3.5+/-1.3 and
      3.1+/-1.4 mm, respectively; P<0.0001). The mean+/-SD of the BCG scar size was
      significantly lower in infants vaccinated with the Tokyo strain than in those
      vaccinated with the 0.1 ml Pasteur-Merieux strain (3.9+/-1.2 vs. 4.3+/-1.1 mm;
      P=0.03) and no significant difference was found between infants receiving the
      Tokyo strain and the 0.05 ml Pasteur-Merieux strain. However, the differences in
      TST size induced by diverse BCG vaccination modalities may not reflect the
      quality of the immunologically induced response in terms of TB protection.

PMID- 16997339
TI  - An in vitro and in silico study on the flavonoid-mediated modulation of the
      transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco
      2 monolayers.
AB  - The present study describes the effect of different flavonoids on the absorption
      of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in
      silico model describing this process taking into account passive diffusion and
      active transport of PhIP. Various flavonoids stimulated the apical to basolateral
      PhIP transport. Using the in silico model for flavone, kaempferol and
      chrysoeriol, the apparent Ki value for inhibition of the active transport to the
      apical side was estimated to be below 53 muM and for morin, robinetin and
      taxifolin between 164 and 268 microM. For myricetin, luteolin, naringenin and
      quercetin, the apparent Ki values were determined more accurately and amounted to
      37.3, 12.2, 11.7 and 5.6 microM respectively. Additional experiments revealed
      that the apical to basolateral PhIP transport was also increased in the presence
      of a typical BCRP or MRP inhibitor with apparent Ki values in the same range as
      those of the flavonoids. This observation together with the fact that flavonoids
      are known to be inhibitors of MRPs and BCRP, corroborates that inhibition of
      these apical membrane transporters is involved in the flavonoid-mediated
      increased apical to basolateral PhIP transport. Based on the apparent Ki values
      obtained, it is concluded that the flavonols, at the levels present in the
      regular Western diet, are capable of stimulating the transport of PhIP through
      Caco-2 monolayers from the apical to the basolateral compartment. This points to
      flavonoid-mediated stimulation of the bioavailability of PhIP and, thus, a
      possible adverse effect of these supposed beneficial food ingredients.

PMID- 16997340
TI  - Deciding which chemical mixtures risk assessment methods work best for what
      mixtures.
AB  - The most commonly used chemical mixtures risk assessment methods involve simple
      notions of additivity and toxicological similarity. Newer methods are emerging in
      response to the complexities of chemical mixture exposures and effects. Factors
      based on both science and policy drive decisions regarding whether to conduct a
      chemical mixtures risk assessment and, if so, which methods to employ. Scientific
      considerations are based on positive evidence of joint toxic action, elevated
      human exposure conditions or the potential for significant impacts on human
      health. Policy issues include legislative drivers that may mandate action even
      though adequate toxicity data on a specific mixture may not be available and risk
      assessment goals that impact the choice of risk assessment method to obtain the
      amount of health protection desired. This paper discusses three important
      concepts used to choose among available approaches for conducting a chemical
      mixtures risk assessment: (1) additive joint toxic action of mixture components;
      (2) toxicological interactions of mixture components; and (3) chemical
      composition of complex mixtures. It is proposed that scientific support for basic
      assumptions used in chemical mixtures risk assessment should be developed by
      expert panels, risk assessment methods experts, and laboratory toxicologists.
      This is imperative to further develop and refine quantitative methods and provide
      guidance on their appropriate applications. Risk assessors need scientific
      support for chemical mixtures risk assessment methods in the form of
      toxicological data on joint toxic action for high priority mixtures, statistical
      methods for analyzing dose-response for mixtures, and toxicological and
      statistical criteria for determining sufficient similarity of complex mixtures.

PMID- 16997341
TI  - Nitrogen:Phosphorus supply ratio may control the protein and total toxin of
      dinoflagellate Alexandrium tamarense.
AB  - The protein and total toxin of dinoflagellate Alexandrium tamarense at the
      exponential growth phase were studied at four N:P supply ratios=8, 16, 24 and 48
      by maintaining the N concentration at 880 microM with variable P concentrations
      without nutrient limitation. Because A. tamarense grew well at all N:P supply
      ratios, they might synthesize RNA which contains high phosphorus and consequently
      low N:P atomic ratio of cells might be retained during exponential growth phase.
      Cellular protein:C ratio and toxin:C ratio depended on N:P supply ratio,
      suggesting that intracellular biochemical composition of A. tamarense might vary
      due to N:P supply conditions. These biochemical changes could not be detected by
      only investigations of cellular N:C atomic ratio which was independent on N:P
      supply ratio. Total cellular toxin contents of A. tamarense increased with
      increasing N:P supply ratio, indicated that total cellular toxin contents of A.
      tamarense might be stimulated by relative P-deficiency. In situ P concentration
      of the Seto Inland Sea of Japan has been reduced since 1980s the environmental
      regulation issued by Japanese Government, and therefore N:P supply ratio of input
      water from adjacent rivers has became higher than the Redfield ratio. The present
      study may suggest that the reduction of P supply into ambient sea water might
      cause A. tamarense to accumulate more toxin within the cell, in result, noxious
      A. tamarense would be more influential to marine organisms in coastal ecosystem.

PMID- 16997342
TI  - Distribution of tetrodotoxin, saxitoxin, and their analogs among tissues of the
      puffer fish Fugu pardalis.
AB  - The anatomical distribution of tetrodotoxin (TTX), saxitoxin (STX) and their
      analogs (TTXs, STXs) in three female and three male specimens of the marine
      puffer fish Fugu pardalis from Miyagi Prefecture, 2005, Japan, were studied. 5
      DeoxyTTX, 11-deoxyTTX, and 5,6,11-trideoxyTTX were quantified by liquid
      chromatography/mass spectrometry (LC/MS) for the first time, and other TTXs and
      STXs were determined by liquid chromatography-fluorescent detection (LC-FLD). As
      a result, 5,6,11-trideoxyTTX was found to be the major TTX analog in all tissues
      tested, whereas 5-deoxyTTX and 11-deoxyTTX were minor components. Especially, in
      female (n=3), the ratios of 5,6,11-trideoxyTTX to total of all TTX analogs
      (mole/mole) in ovaries (mean+/-SD, 0.42+/-0.055) were significantly larger than
      those in livers (0.17+/-0.025) (P<0.05). In contrary, the ratios of 4,9
      anhydroTTX to total of all TTX analogs in livers (0.27+/-0.047) were
      significantly larger than those in ovaries (0.073+/-0.040) (P<0.01). The ratios
      of TTX to total of all TTX analogs were not significantly different between
      ovaries (0.47+/-0.078) and livers (0.55+/-0.067). In male (n=3), all these ratios
      were not significantly different between livers and testis. 4-S-CysteinylTTX was
      detected in liver, spleen, gall, and intestine in 1-6mole% of total of all TTX
      analogs, supporting our previous hypothesis that 4-S-cysteinylTTX is a metabolite
      of TTX.

PMID- 16997343
TI  - Distinguishing molecular forms of HIV-1 in Asia with a high-throughput,
      fluorescent genotyping assay, MHAbce v.2.
AB  - High-resolution HIV-1 genotyping of large sample sets is crucial to define the
      evolving and dynamic epidemics in Asia. Here we present MHAbce v.2, a multi
      region hybridization assay that individually discriminates subtypes B, C,
      CRF01_AE, and virtually all of their described recombinants, based on real-time
      PCR using subtype-specific TaqMan probes in 8 regions throughout the viral
      genome. In a validation panel (n=70), the assay performed with a sensitivity of
      95.7% and specificity of 99.8%. The assay was field-tested on samples from a
      retrospective MTCT cohort (n=180; Lampang Province, Northern Thailand; 1996
      1998). 177/180 of the samples were typeable, and 94.4% were typed as CRF01_AE.
      The remaining strains represented even proportions of subtype B and B/CRF01_AE
      recombinants and were confirmed by sequencing, revealing early links between the
      heterosexual and IDU HIV-1 epidemics in Thailand. MHAbce v.2, with an area of
      application including China, India, Southeast Asia, and the Pacific Rim, can be
      used to develop a comprehensive and detailed picture of this important component
      of the HIV/AIDS pandemic.

PMID- 16997344
TI  - A conserved region of the herpes simplex virus type 1 tegument protein VP22
      facilitates interaction with the cytoplasmic tail of glycoprotein E (gE).
AB  - Herpes simplex virus type 1 (HSV-1) virions, contain a proteinaceous layer termed
      the tegument that lies between the nucleocapsid and viral envelope. Current
      evidence suggests that viral glycoprotein tails play a role in the recruitment of
      tegument-coated capsids to the site of final envelopment; vesicles derived from
      the trans-Golgi network. We have identified an interaction between VP22, an
      abundant tegument protein and the cytoplasmic tail of glycoprotein E (gE). This
      interaction was identified by coimmunoprecipitation studies and confirmed by a
      glutathione-S-transferase (GST) pulldown from infected cell lysates. Truncation
      mutagenesis suggests that residues 165-270 of VP22 facilitate the interaction
      with the cytoplasmic tail of gE. In fact, this region of VP22 is sufficient to
      bind to gE in the absence of additional viral proteins. Using a
      transfection/infection-based virion incorporation assay, residues 165-270 of VP22
      fused to GFP competed efficiently with wild-type VP22 for packaging into
      assembling virus particles.

PMID- 16997345
TI  - Laboratory investigations for the morphologic, pharmacokinetic, and anti
      retroviral properties of indinavir nanoparticles in human monocyte-derived
      macrophages.
AB  - The effectiveness of anti-retroviral therapies (ART) depends on its ultimate
      ability to clear reservoirs of continuous human immunodeficiency virus (HIV)
      infection. We reasoned that a principal vehicle for viral dissemination, the
      mononuclear phagocytes could also serve as an ART transporter and as such improve
      therapeutic indices. A nanoparticle-indinavir (NP-IDV) formulation was made and
      taken up into and released from vacuoles of human monocyte-derived macrophages
      (MDM). Following a single NP-IDV dose, drug levels within and outside MDM
      remained constant for 6 days without cytotoxicity. Administration of NP-IDV when
      compared to equal drug levels of free soluble IDV significantly blocked induction
      of multinucleated giant cells, production of reverse transcriptase activity in
      culture fluids and cell-associated HIV-1p24 antigens after HIV-1 infection. These
      data provide "proof of concept" for the use of macrophage-based NP delivery
      systems for human HIV-1 infections.

PMID- 16997346
TI  - Only those genes of the KIAA1245 gene subfamily that contain HERV(K) LTRs in
      their introns are transcriptionally active.
AB  - Insertion of LTRs into some genome locations might seriously affect regulation of
      the neighboring genes expression. This hypothesis is widely accepted but,
      however, not confirmed directly. Earlier, we have identified a family of closely
      related genes highly similar to the KIAA1245 mRNA counterpart. This family
      included a subfamily of genes some of which contained and the others lacked an
      LTR in their structure. We compared transcription of several closely related
      genes of the subfamily differing in the presence or absence of LTRs. Only LTR
      containing genes were transcribed in transformed cell lines, tumorous and
      embryonic human tissues, whereas LTR-lacking genes remained silent. Since the
      genes were in the same intracellular microenvironment, we suggested that this
      effect was most probably due to intrinsic cis-characteristics of integrated LTRs
      and confirmed this by demonstrating high enhancer activity of KIAA1245 LTRs. The
      expression of the LTR-containing genes in embryonic tissues might suggest their
      involvement in evolutionary events during primate speciation.

PMID- 16997347
TI  - Luminance-contrast mechanisms in humans: visual evoked potentials and a nonlinear
      model.
AB  - Isolated-checks were luminance-modulated temporally to elicit VEPs. Bright or
      dark checks were used to drive ON or OFF pathways, and low or high-contrast
      conditions were used to emphasize activity from magnocellular or parvocellular
      pathways. Manipulation of stimulus parameters and frequency analysis of the VEP
      were performed to obtain spatial and contrast-response functions. A biophysical
      explanation is offered for why the opposite polarity stimuli drive selectively ON
      and OFF pathways in primary visual cortex, and a lumped biophysical model is
      proposed to quantify the data and characterize changes in the dynamics of the
      system with contrast given a limited number of parameters. Response functions
      were found to match the characteristics of the targeted pathways.

PMID- 16997348
TI  - Breakeven costs for distributed advanced technology water-treatment systems.
AB  - Breakeven costs associated with the strategic distribution of advanced treatment
      units in a water supply network to manage network-derived water quality
      degradation were investigated. Disinfections by-product (DBP) formation was used
      as a representative water quality degradation parameter. A basic DBP formation
      model was used to predict that fraction of residential service population
      receiving water degraded below required quality levels within a hypothetical
      water utility service population. The costs of upgrading centralized treatment
      facilities to meet DBP water quality standards were estimated and then
      apportioned over that population fraction to estimate breakeven or equivalent
      cost allowances for an alternative distributed treatment approach. Breakeven
      costs for single-connection treatment units were calculated for a range of
      service populations. A sensitivity analysis of the impacts of various network
      parameters on breakeven costs revealed the existence of singularities--sudden
      shifts in optimal technology selection--resulting from relatively small
      variations in required treatment levels.

PMID- 16997349
TI  - Bioconcentration, biomagnification and metabolism of 14C-terbutryn and 14C
      benzo[a]pyrene in Gammarus fossarum and Asellus aquaticus.
AB  - The contribution of bioconcentration and biomagnification of 14C-terbutryn and
      14C-benzo[a]pyrene via food and water to the bioaccumulation in Gammarus fossarum
      and Asellus aquaticus was investigated in single species-tests. In this
      investigation the uptake of 14C-terbutryn and 14C-benzo[a]pyrene via food and
      water by G. fossarum (L.) and A. aquaticus (L.) was examined. Bioconcentration
      factors (BCFs) and biomagnification factors (BMFs) were determined. Calculated
      BCFs were clearly higher than BMFs, indicating that water is the primary route of
      uptake. The uptake of terbutryn and benzo[a]pyren via water in G. fossarum and A.
      aquaticus is faster than uptake via food. The elimination and metabolism of the
      two chemicals by G. fossarum and A. aquaticus were studied. Terbutryn was
      eliminated almost completely in both species. In general, the elimination of
      terbutryn from G. fossarum and A. aquaticus was fast with half-life of 5 h. The
      elimination of terbutryn by G. fossarum after biomagnification is slower than
      after bioconcentration. No difference was found in elimination of terbutryn by A.
      aquaticus after biomagnification and after bioconcentration. Metabolites of
      terbutryn in G. fossarum and A. aquaticus were analyzed by HPLC. After the
      bioconcentration experiment a higher percentage of metabolites was found in G.
      fossarum than in A. aquaticus. This was confirmed for the experiment with uptake
      via food. The spectrum of metabolites was similar in both species, with
      hydroxyterbutryn being the major metabolism product in water. 14C-B[a]P could
      nearly completely be eliminated by G. fossarum (rest of activity 2%) after uptake
      via water. 14C-B[a]P could not be eliminated by G. fossarum and A. aquaticus
      after uptake via food. The metabolite could not be identified.

PMID- 16997350
TI  - PCB mass transfer coefficients determined by application of a water surface
      sampler.
AB  - A water surface sampler (WSS) was employed in combination with greased surface
      deposition plates (GSDPs) to measure the particulate dry deposition and gas
      exchange of polychlorinated biphenyls (PCBs) in Chicago, IL. Vapor phase PCB
      fluxes were calculated by subtracting the particulate fluxes obtained from GSDPs
      from total (particulate+gas) fluxes obtained from the WSS. Vapor phase PCB fluxes
      were divided by ambient air concentrations measured with a high volume sampler to
      calculate overall gas phase PCB mass transfer coefficients (K(G)). The calculated
      average PCB MTC was 0.54+/-0.47 cm s(-1). This experimentally determined average
      gas phase overall mass transfer coefficient, K(G), agreed well with the ones
      reported from studies using similar techniques and agreed well with modeled
      values obtained using MTC correlations developed for the WSS.

PMID- 16997351
TI  - A field trial for an ex-situ bioremediation of a drilling mud-polluted site.
AB  - The remediation of drilling mud-polluted sites in the Southeast of Mexico is a
      top priority for Mexican oil industry. The objective of this work was to find a
      technology to remediate these sites. A field trial was performed by composting in
      biopiles, where four 1ton soil-biopiles were established, one treatment in
      triplicate and one unamended biopile. Amended biopiles were added with nutrients
      to get a C/N/P ratio of 100/3/0.5 plus a bulking agent (straw) at a soil/straw
      ratio of 97/3. Moisture content was maintained around 30-35%. Results showed
      that, after 180 d, total petroleum hydrocarbon (TPH) concentrations decreased
      from 99300+/-23000mgTPHkg(-1) soil to 5500+/-770mgTPHkg(-1) for amended biopiles
      and to 22900+/-7800mgTPHkg(-1) for unamended biopile. An undisturbed soil control
      showed no change in TPH concentrations. Gas chromatographic analysis showed
      residual alkyl dibenzothiophene type compounds. Highest bacterial counts were
      observed during the first 30 d which correlated with highest TPH removal, whereas
      fungal count increased at the end of the experimentation period. Results
      suggested an important role of the straw, nutrient addition and water content in
      stimulating aerobic microbial activity and thus hydrocarbon removal. This finding
      opens an opportunity to remediate old polluted sites with recalcitrant and high
      TPH concentration.

PMID- 16997352
TI  - Multiple thromboembolic events in fetofetal transfusion syndrome in triplets
      contributing to the understanding of pathogenesis of hydranencephaly in
      combination with polymicrogyria.
AB  - Over the last 180 years, several theories concerning the origin of
      hydranencephaly have been proposed with an emphasis on infectious, aplastic, and
      vascular etiologies. In this report, we present a case of triplets with fetofetal
      transfusion syndrome of which 2 fetuses (1 and 2) developed almost similar
      hydranencephaly, whereas the third exhibited the features of a fetus papyraceus
      (3). In the monochorial triamniotic placenta, multiple arteriovenous anastomoses
      were detected, representing a probable route for the transmission of thrombi
      originating from fetus 3 causing visceral lesions in fetus 2. Hydranencephaly was
      histologically characterized by necrosis, macrophage invasion, and endothelial
      proliferation. In addition, polymicrogyria was seen in fetuses 1 and 2. The
      combination of multiple visceral thromboembolic events and the death of fetus 3
      approximately in the 11th week of gestation suggested a vascular thrombotic
      pathogenesis of hydranencephaly. Polymicrogyria can be considered as
      postmigratory laminar necrosis. Our findings contribute to the pathogenetic
      understanding of combined hydranencephaly and polymicrogyria.

PMID- 16997353
TI  - Comprehensive expression analysis of L-dopa decarboxylase and established
      neuroendocrine markers in neoadjuvant hormone-treated versus varying Gleason
      grade prostate tumors.
AB  - Current hormone withdrawal therapies used for treatment of advanced prostate
      cancer lead to androgen-independent tumor growth. Increased prostatic
      neuroendocrine (NE) cell density has been implicated in promoting progression of
      prostate cancer, but the process by which this occurs remains unclear. The aim of
      this study was to determine whether there is an association of increased NE
      differentiation with neoadjuvant hormone therapy and Gleason grade. Using
      adjacently sectioned tissue microarrays, the expression profile of novel and
      known NE markers were monitored. L-Dopa decarboxylase (DDC), a catecholamine
      synthesis enzyme and androgen receptor (AR) coregulator protein, was identified
      as an additional NE marker of prostate cancer. Immunohistochemical analysis of
      DDC with the established NE markers, chromogranin A and bombesin, revealed a
      significant increase in NE differentiation after 6 months of hormone therapy and
      after progression to androgen independence but no apparent correlation with
      Gleason grade. In addition, dual immunofluorescence analysis revealed that
      approximately 55% of the mixed population of DDC- and chromogranin A-expressing
      NE cells continue to express AR. Taken together, these results suggest that the
      increase of NE differentiation in prostate cancers depends specifically on
      duration of hormone therapy. This increase may be due to the transdifferentiation
      of AR-expressing epithelial-derived adenocarcinoma cells into an NE cell
      phenotype.

PMID- 16997354
TI  - Direct and indirect evidence for the reversibility of cirrhosis.
AB  - The aim of this study was to assess the reversibility of cirrhosis after therapy
      in a large series of patients with cirrhosis from various etiologies. We
      performed a retrospective study of 113 patients with biopsy-proven cirrhosis who
      underwent specific therapy and follow-up biopsies. Two pathologists performed
      blinded analyses of indirect biochemical and morphological signs of cirrhosis.
      Fourteen (12.4%) of the 113 cirrhotic patients had biopsy-proven disappearance of
      cirrhosis, defined as a decrease of 2 or greater in their METAVIR fibrosis score:
      8 were related to hepatitis C virus, 3 to hepatitis B virus, and 3 to autoimmune
      cirrhosis. Necro-inflammatory activity decreased from 2.4 +/- 0.65 to 0.85 +/-
      0.9 (P = .004), and fibrosis from 4 to 1.7 +/- 0.61 (P = .001). Prothrombin time
      (n = 1), platelet count (n = 2), serum albumin level (n = 2), and ultrasound
      abnormalities (n = 6) normalized in patients who had initial abnormalities.
      Hyaluronic acid and procollagen type III serum level decreased in all. In the 11
      patients with regression of viral cirrhosis, 2 were nonresponders and 9 were
      responders, including 2 relapsers. The 3 patients with regressive autoimmune
      cirrhosis were complete responders to immunosupressive therapy. Using repeated
      liver biopsies, clinicobiochemical, radiologic, and endoscopic tests, we provide
      evidence for potential reversibility of cirrhosis after long-lasting suppression
      of the necro-inflammatory activity of liver disease.

PMID- 16997355
TI  - Functional significance of the microstructural detail of the primate dentino
      enamel junction: a possible example of exaptation.
AB  - In primate teeth, the dentino-enamel junction (DEJ) exhibits a scalloped
      appearance, the functional importance of which has been the subject of various
      suggestions and speculations. Simplified finite-element (FE) models of DEJ
      microanatomy were created, both in 2D and 3D, and their biomechanical behavior
      was tested and compared. Consistently, the models with the scalloped DEJ,
      although having higher maximum tensile stresses than the straight DEJ models,
      showed discontinuous concentrations of stress. In straight DEJ models, tensile
      stresses act at the DEJ over continuous areas in a direction, which would push
      the two tissues apart, thus leading to delamination of the DEJ. Perhaps even more
      important, in the scallop model, the net-compression towards the DEJ was
      consistently higher than net-tension away from it. As a consequence, dentine and
      enamel would be pushed towards each other during loading (i.e., during
      mastication). These findings suggest that the scalloped nature of the DEJ confers
      a biomechanical advantage to the integrity of the tooth during mastication.
      Furthermore, there exists a correlation between pronounced prism decussation and
      scallop magnitude, suggesting that scallops may have been selected for in
      response to high bite forces. However, given the equivocal relationship between
      scallops and presumed bite force across mammalian taxa, we propose that scallops
      could in fact be exaptations.

PMID- 16997356
TI  - Neuroendocrine cells in the vestibular glands of the genital tract of cows and
      pigs.
AB  - The presence of neuroendocrine (NE) cells producing biogenic amines and hormonal
      peptides has been investigated in the vestibular glands of the genital tracts of
      cows and pigs using immunohistochemistry. NE cells containing chromogranin A-,
      serotonin-, cholecystokinin- and somatostatin-immunoreactive material were found
      in both major and minor vestibular glands. Such cells were numerous, scattered in
      the acini and excretory duct epithelium, small in size and rounded, triangular or
      bipolar in shape. The function of the NE vestibular cells has been related to the
      secretory activity of the glands and to a sexual climax induction mechanism
      involving the stimulation of 5HT(3) receptors of vestibular nociceptor nerve
      fibers. The role of NE cells in small cell carcinomas of the vestibular glands is
      a topic for further investigation owing to possible parallelism between this type
      of tumor and the small cell carcinoma of the human prostate.

PMID- 16997357
TI  - Health status, behavior, and care utilization in the Geneva Gay Men's Health
      Survey.
AB  - BACKGROUND: Recent reviews and studies suggest distinctive health needs among gay
      men. METHODS: Swiss residents in the Geneva Gay Men's Health Survey (GGMHS,
      n=477) were matched with controls from the Swiss Health Survey (SHS, n=477) along
      sex, age, nationality, and region of residence and compared along standard
      indicators of health status, health behaviors, and health care utilization. Both
      health surveys were conducted in 2002 using probability sampling--i.e., time
      space sampling (GGMHS) and household probability telephone sampling (SHS).
      RESULTS: Although gay men were significantly less likely to be overweight
      (adjusted odds ratio (AOR)=0.54), they reported significantly more and severe
      physical symptoms (AOR ranged from 1.72 to 9.21), short-term disability
      (AOR=2.56), risk factors for chronic disease--i.e., high cholesterol, high blood
      pressure, high glucose, and smoking (AOR ranged from 1.67 to 3.89), and greater
      health services utilization (AOR ranged from 1.62 to 4.28), even after adjustment
      for differences in socio-demographic characteristics and health behaviors.
      CONCLUSIONS: Evidence of greater morbidity among a community sample of gay men
      along standard health indicators underlines the relevance of sexual orientation
      as a socio-demographic indicator in public health in general and in the health
      inequalities discourse in particular.

PMID- 16997358
TI  - Food store availability and neighborhood characteristics in the United States.
AB  - OBJECTIVE: This study provides a multivariate analysis of the availability of
      food store outlets in the US and associations with neighborhood characteristics
      on race, ethnicity and socioeconomic status (SES). METHOD: Commercial food store
      outlet data are linked across 28,050 zip codes to Census 2000 data. Multivariate
      regression analyses are used to examine associations between the availability of
      chain supermarkets, non-chain supermarkets, grocery stores and convenience stores
      and neighborhood characteristics on race, ethnicity and SES including additional
      controls for population size, urbanization and region. RESULTS: Low-income
      neighborhoods have fewer chain supermarkets with only 75% (p<0.01) of that
      available in middle-income neighborhoods. Even after controlling for income and
      other covariates, the availability of chain supermarkets in African American
      neighborhoods is only 52% (p<0.01) of that in White neighborhoods with even less
      relative availability in urban areas. Hispanic neighborhoods have only 32%
      (p<0.01) as many chain supermarkets compared to non-Hispanic neighborhoods. Non
      chain supermarkets and grocery stores are more prevalent in low-income and
      minority neighborhoods. CONCLUSION: The study results highlight the importance of
      various potential public policy measures for improving access to supermarkets
      that may serve to reduce systematic local area barriers that are shown to exist
      by race, ethnicity and income.

PMID- 16997359
TI  - Carbohydrates and the diet-atherosclerosis connection--more between earth and
      heaven. Comment on the article "The atherogenic potential of dietary
      carbohydrate".

PMID- 16997360
TI  - A biomarker of exposure to environmental tobacco smoke (ETS) and Ernst Wynder's
      opinion about ETS and lung cancer.
AB  - Ernst Wynder did not believe that environmental tobacco smoke (ETS), also known
      as secondhand smoke, was a cause of lung cancer because his own data did not
      support this. His view on the issue may have begun to change with our initial
      studies, carried out at the American Health Foundation, showing that metabolites
      of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) were present in the urine of non-smokers exposed to ETS. The
      metabolites - 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its
      glucuronides (NNAL-Glucs) - have now emerged as leading biomarkers for the study
      of carcinogen exposure in non-smokers exposed to ETS. Subsequent work has
      consistently demonstrated elevated levels of NNAL plus NNAL-Glucs in the urine of
      people exposed to ETS in various field studies and throughout life. These studies
      strongly support the epidemiologic data demonstrating that ETS exposure causes
      lung cancer in non-smokers and have likely had an impact on tobacco control.

PMID- 16997361
TI  - Biosketch of Ernst Ludwig Wynder.

PMID- 16997362
TI  - The emerging case-control study: lung cancer in relation to tobacco smoking.
AB  - Two influential case-control studies that clearly implicated cigarette smoking as
      a cause of lung cancer are reviewed in terms of their respective strengths and
      weaknesses. The findings from a U.S. study reported in 1950 by Wynder and Graham
      were strikingly similar to those arising from a U.K. study reported later that
      year by Doll and Hill. The methodological rigor of these investigations
      effectively ruled out alternatives to smoking as plausible explanations for the
      increased risk, although additional investigations in animals and man were needed
      to buttress the original results. The exceptionally high relative risk of lung
      cancer that was found has had far-reaching medical, social, and economic
      consequences.

PMID- 16997363
TI  - Ernst Wynder and preventive medicine.

PMID- 16997364
TI  - Ernst L. Wynder, the entrepreneurial epidemiologist.
AB  - This article provides recollections and commentary regarding the lifelong
      achievements of the founding editor of Preventive Medicine.

PMID- 16997365
TI  - Ernst Wynder: citation analysis.
AB  - Ernst Wynder published nearly 800 papers during his lifetime. I used the ISI Web
      of Science to analyze his publications and the subsequent literature citing his
      work. More than half of his papers were published in just ten journals, including
      Cancer, Preventive Medicine (which he founded and edited), JNCI, and Cancer
      Research. The 87 papers in Cancer covered all of the major cancer sites including
      breast, colon, lung, and prostate, and many others. Twenty-five papers and one
      book were cited in over 200 publications. His publications included 441 co
      authors from a broad range of scientific disciplines.

PMID- 16997366
TI  - A study of syntactic processing in aphasia II: neurological aspects.
AB  - This paper presents the results of a study of the effects of left hemisphere
      strokes on syntactically-based comprehension in aphasic patients. We studied 42
      patients with aphasia secondary to left hemisphere strokes and 25 control
      subjects for the ability to assign and interpret three syntactic structures
      (passives, object extracted relative clauses, and reflexive pronouns) in
      enactment, sentence-picture matching and grammaticality judgment tasks. We
      measured accuracy, RT and self-paced listening times in SPM and GJ. We obtained
      magnetic resonance (MR) and 5-deoxyglucose positron emission tomography (FDG PET)
      data on 31 patients and 12 controls. The percent of selected regions of interest
      (ROIs) that was lesioned on MR and the mean normalized PET counts per voxel in
      ROIs were calculated. In regression analyses, lesion measures in both perisylvian
      and non-perisylvian ROIs predicted performance. Patients who performed at similar
      levels behaviorally had lesions of very different sizes, and patients with
      equivalent lesion sizes varied greatly in their level of performance. The data
      are consistent with a model in which the neural tissue that is responsible for
      the operations underlying sentence comprehension and syntactic processing is
      localized in different neural regions in different individuals.

PMID- 16997367
TI  - An intentional stance modulates the integration of gesture and speech during
      comprehension.
AB  - The present study investigates whether knowledge about the intentional
      relationship between gesture and speech influences controlled processes when
      integrating the two modalities at comprehension. Thirty-five adults watched short
      videos of gesture and speech that conveyed semantically congruous and incongruous
      information. In half of the videos, participants were told that the two
      modalities were intentionally coupled (i.e., produced by the same communicator),
      and in the other half, they were told that the two modalities were not
      intentionally coupled (i.e., produced by different communicators). When
      participants knew that the same communicator produced the speech and gesture,
      there was a larger bi-lateral frontal and central N400 effect to words that were
      semantically incongruous versus congruous with gesture. However, when
      participants knew that different communicators produced the speech and gesture-
      that is, when gesture and speech were not intentionally meant to go together--the
      N400 effect was present only in right-hemisphere frontal regions. The results
      demonstrate that pragmatic knowledge about the intentional relationship between
      gesture and speech modulates controlled neural processes during the integration
      of the two modalities.

PMID- 16997368
TI  - Thirty-five percent carbamide peroxide application causes in vitro
      demineralization of enamel.
AB  - OBJECTIVES: The objective of this in vitro study was to investigate whether a
      high concentration 'in-office' bleaching agent affected the mineral content of
      enamel and dentin. METHODS: A commercially available 35% carbamide peroxide
      bleaching agent was applied for 2h to sectioned teeth (n=11). Specimens were then
      immersed in artificial saliva at 37 degrees C for a further 24h to simulate the
      oral environment. Tomographic images of these sections were obtained (micro-CT
      80, Scanco, Switzerland) prior to and post-bleach application. Eight three
      dimensional regions of interest (ROI), starting from the enamel surface extending
      to the dentinoenamel junction, were selected for each section. The hydroxyapatite
      equivalent mineral concentrations (g/cm(3)) of the ROIs were calculated. Any
      changes in mineral content as a consequence of the bleaching procedure were
      calculated in relation to each ROI. RESULTS: There was a significant reduction in
      the mineral content of enamel specimens post-bleach application extending to a
      depth of 250microm (paired t-test, p<0.05); this reduction in mineral content was
      greatest in the ROI's closest to the tooth surface. There was, however, no
      significant difference in the mineral content of dentin as a consequence of
      bleaching. SIGNIFICANCE: This in vitro study has shown that significant
      demineralization of enamel occurred following bleaching with 35% carbamide
      peroxide. The concept that 'in-office' bleaching is a non-destructive cosmetic
      procedure should be reconsidered.

PMID- 16997369
TI  - Preparation and application of poly(N,N-dimethylacrylamide-co-acrylamide) and
      poly(N-isopropylacrylamide-co-acrylamide)/kappa-Carrageenan hydrogels for
      immobilization of lipase.
AB  - In the present of this study, two novel polymeric matrixes that are poly(N,N
      dimethylacrylamide-co-acrylamide) and poly(N-isopropylacrylamide-co
      acrylamide)/kappa-Carrageenan was synthesized and applied for immobilization of
      lipase. For the immobilization of enzyme, two different immobilization procedures
      have been carried out via covalently binding and entrapment methods. On the free
      and immobilized enzymes activities, optimum pH, temperature, storage and thermal
      stability was investigated. The optimum temperature for free, covalently
      immobilized and entrapped enzymes was found to be 30, 35 and 30 degrees C,
      respectively. Optimum pH for both free and immobilized enzymes was also observed
      at pH 8. Maximum reaction rate (Vmax) and Michaelis-Menten constant (Km) were
      determined for free and immobilized lipases. Furthermore, the reuse numbers of
      immobilized enzymes also studied. It was observed that after 40th use in 5 days,
      the retained activities for covalently immobilized and entrapped lipases were
      found as 39% and 22%, respectively. Storage and thermal stability of enzyme was
      also increased by as a result of immobilization procedures.

PMID- 16997370
TI  - Interactions between flavonoids and hemoglobin in lecithin liposomes.
AB  - In this paper, the binding of flavonoids (quercetin and rutin) to hemoglobin (Hb)
      have been investigated by fluorescence, absorption spectroscopy and circular
      dichroism (CD) spectroscopy. The binding parameters and binding mode between
      flavonoids and Hb are determined and the results of CD and synchronous
      fluorescence spectra indicate a conformational change of Hb with addition of
      flavonoids. The effects of lecithin liposomes on the binding parameter of
      quercetin and rutin to Hb are also studied. When incorporated into liposome,
      flavonoids can reduce the fluorescence of tryptophanyl residues of Hb to a lesser
      extent. The difference of the structure characteristics between quercetin and
      rutin has a significant effect on their binding affinity for Hb.

PMID- 16997371
TI  - Adipogenesis of murine embryonic stem cells in a three-dimensional culture system
      using electrospun polymer scaffolds.
AB  - A mechanistic understanding of adipose tissue differentiation is critical for the
      treatment and prevention of obesity and type 2 diabetes. Conventional in vitro
      models of adipogenesis are preadipocytes or freshly isolated adipocytes grown in
      two-dimensional (2D) cultures. Optimal results using in vitro tissue culture
      models can be expected only when adipocyte models closely resemble adipose tissue
      in vivo. Thus the design of an in vitro three-dimensional (3D) model which
      faithfully mimics the in vivo environment is needed to effectively study
      adipogenesis. Pluripotent embryonic stem (ES) cells are a self-renewing cell type
      that can readily be differentiated into adipocytes. In this study, a 3D culture
      system was developed to mimic the geometry of adipose tissue in vivo. Murine ES
      cells were seeded into electrospun polycaprolactone scaffolds and differentiated
      into adipocytes in situ by hormone induction as demonstrated using a battery of
      gene and protein expression markers along with the accumulation of neutral lipid
      droplets. Insulin-responsive Akt phosphorylation, and beta-adrenergic stimulation
      of cyclic AMP synthesis were demonstrated in ES cell-derived adipocytes.
      Morphologically, ES cell-derived adipocytes resembled native fat cells by
      scanning electron and phase contrast microscopy. This tissue engineered ES cell
      matrix model has potential uses in drug screening and other therapeutic
      developments.

PMID- 16997372
TI  - Effect of gypsum on proliferation and differentiation of MC3T3-E1 mouse
      osteoblastic cells.
AB  - Recently, calcium sulfate dihydrate has been demonstrated as safe biodegradable
      osteoconductive bone void filler. However, its exact mechanism of action on bone
      cells is yet unknown. In this study, the influence of gypsum on gene expression
      and proliferation of MC3T3-E1 mouse pre-osteoblastic cells was investigated.
      Cells were cultured on gypsum disc, slice, polymethylmethacrylate (PMMA), or
      plastic culture plate for 15 days. Cell viability, alkaline phosphatase (ALP)
      activity and expression profile of 15 genes involved in bone metabolism were
      measured in cultures. Cell proliferation on gypsum was increased by almost 2
      fold, while an inhibitory effect of PMMA on proliferation rate of osteoblasts was
      noted. Cells cultured on gypsum disc surface exhibited an increased ALP activity
      and markedly different gene expression profile. Quantitative real-time PCR data
      indicated the expression of genes that might provide a basis for an
      osteoinductive potential. MC3T3-E1 cells expressed genes typical of bone fracture
      healing like type II collagen and fibronectin 1. These effects might be related
      to the calcium content of gypsum and mediated likely via SMAD3. Our results
      suggest that gypsum can support new bone formation by its calcium content and
      modulatory effect on gene expression profile of bone cells.

PMID- 16997373
TI  - Complex karyotype including chromosomal translocation (8;14) (q24;q32) in one
      case with B-cell prolymphocytic leukemia.
AB  - We report a case of a 64-year-old white female patient, who presented with
      symptomatic anemia (Hgb: 6.8g/dl), thrombocytopenia (platelets: 94,000/mcl) and
      leukocytosis (WBC: 156,000/mcl). Peripheral blood smear revealed markedly
      increased white blood cell count with predominance of atypical lymphoid cells of
      intermediate size, moderately dense chromatin, and prominent large single
      nucleoli. Bone marrow aspirate smear showed predominance (78%) of atypical
      lymphoid cells morphologically identical to those seen in the peripheral blood.
      The bone marrow core biopsy was hypercellular and packed with prominent
      infiltrate of prolymphocytes. Immunophenotypic analysis revealed a population of
      monoclonal cells (75% of all -erythroid cells) characterized by CD45+, CD19+,
      CD20+, CD5+, HLA-DR+, CD10-, CD23+/-, CD38+ and FMC7-. The abnormal cells were
      restricted to kappa light chain immunoglobulin with low intensity. Cytogenetic
      study showed an abnormal clone of eight cells with the following karyotype: 45,X,
      X,add(8)(p11.2),t(8;14)(q24;q32),add(20)ql3[8]/46,XX[12]. The relative rarity of
      B-PLL and the heterogeneity of clinical and laboratory parameters make it
      difficult to define the natural history and prognosis in all cases. The optimal
      treatment for B-PLL is still unknown and to date there are no reports of
      chromosomal abnormalities as a prognostic factor. The patient was treated with
      six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP).
      Complete remission was achieved according to the criteria defined by National
      Cancer Institute Working Group for CLL.

PMID- 16997374
TI  - TraA is required for megaplasmid conjugation in Rhodococcus erythropolis AN12.
AB  - Pulsed-field gel electrophoresis (PFGE) revealed three previously uncharacterized
      megaplasmids in the genome of Rhodococcus erythropolis AN12. These megaplasmids,
      pREA400, pREA250, and pREA100, are approximately 400, 250, and 100kb,
      respectively, based on their migration in pulsed-field gels. Genetic screening of
      an AN12 transposon insertion library showed that two megaplasmids, pREA400, and
      pREA250, are conjugative. Mobilization frequencies of these AN12 megaplasmids to
      recipient R. erythropolis SQ1 were determined to be approximately 7x10(-4) and
      5x10(-4) events per recipient cell, respectively. It is known for other bacterial
      systems that a relaxase encoded by the traA gene is required to initiate DNA
      transfer during plasmid conjugation. Sequences adjacent to the transposon
      insertion in megaplasmid pREA400 revealed a putative traA-like open reading
      frame. A targeted gene disruption method was developed to generate a traA
      mutation in AN12, which allowed us to address the role of the traA gene product
      for Rhodococcus megaplasmid conjugation. We found that the AN12 traA mutant is no
      longer capable of transferring the pREA400 megaplasmid to SQ1. Furthermore, we
      confirmed that the conjugation defect was specifically due to the disruption of
      the traA gene, as pREA400 megaplasmid conjugation defect is restored with a
      complementing copy of the traA gene.

PMID- 16997375
TI  - Seasonal testosterone UDP-glucuronosyltransferase activity and biliary steroids
      in Eurasian perch: response to leachate exposure.
AB  - In previous studies there was evidence of endocrine disruption in fish in
      waterways contaminated with leachate from a Swedish landfill. Symptoms included
      fewer sexually mature (SM) female perch (Perca fluviatilis), distinct sores,
      reduced gonadosomatic index, and decreased plasma androgen levels. Based on
      previous findings it was hypothesized that the decrease in plasma androgen
      concentrations could have been caused by increased steroid excretion. Therefore,
      testosterone UDP-glucuronosyl transferase (UDPGT) activity and biliary steroids
      were measured in SM and sexually immature (SIM) female perch during one
      reproductive cycle. UDPGT activity in exposed fish did not differ from reference
      fish and was similar in both SM and SIM female perch. Since androgen levels in
      SIM fish usually are much lower than in SM fish, this indicates expression of
      testosterone UDPGT irrespective of substrate availability. There was no general
      increase in biliary steroids in exposed female perch. Biliary steroid levels
      correlated with corresponding plasma steroid levels. In conclusion, the reduced
      androgen levels in exposed female perch are most likely not caused by increased
      steroid excretion.

PMID- 16997376
TI  - Workshop cluster 1, a gammadelta T cell specific receptor is phosphorylated and
      down regulated by activation induced Src family kinase activity.
AB  - Workshop cluster 1(+) gamma delta (WC1(+)gammadelta) T cells have been shown to
      play important roles in the immune response to infections. WC1 is a transmembrane
      glycoprotein, uniquely expressed on the surface of gammadelta T cells of
      ruminants and pigs. A role for WC1 in inducing a reversible growth arrest of
      gammadelta T cells has been previously demonstrated. WC1-induced growth
      inhibition has been shown to be overcome following gammadelta T cell activation
      with Concanavalin A (Con A). However, molecular mechanism(s) by which WC1
      signalling might be modulated following activation have not been elucidated. In
      this paper we show that Con A activation of bovine lymphocytes induces the
      tyrosine phosphorylation of WC1 in a Src-family kinase-dependent manner. Src
      family kinases also phosphorylated WC1 in a COS-7 co-transfection system.
      Furthermore, a glutathione-S-transferase (GST)-WC1 cytoplasmic domain fusion
      protein was directly phosphorylated by recombinant Lck (rLck) in vitro. The
      Y(1303) of WC1 was identified by mutational analysis as the only one of the five
      WC1 tyrosine residues to be critical for Src family phosphorylation. The
      importance of activation-induced Src family activity for WC1 function was
      investigated with the Src-family specific inhibitor PP2. These studies show that
      the surface levels of WC1 are down regulated in a Src-family-dependent manner
      following activation of bovine lymphocytes. Down regulation of surface WC1 was
      accompanied by a Src-family-dependent accumulation of intracellular WC1. These
      data show that WC1 is modulated by activation-induced tyrosine phosphorylation
      thus providing a new insight into the signalling mechanisms by which WC1 and
      gammadelta T cell activation are regulated in this important and unique cell
      population.

PMID- 16997377
TI  - Studies on the activity of three palladium(II) compounds of the form: trans
      PdL2Cl2 where L=2-hydroxypyridine, 3-hydroxypyridine, and 4-hydroxypyridine.
AB  - Three planaraminepalladium(II) complexes of the form: trans-PdCl(2)L(2), code
      named TH5, TH6 and TH7 where L=3-hydroxypyridine, 2-hydroxypyridine and 4
      hydroxypyridine respectively have been investigated for antitumour activity
      against ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R).
      Although the compounds are generally found to be less active than cisplatin, they
      are often found to be more active against the resistant cell lines than the
      parent cell line. Among TH5, TH6 and TH7, TH6 which has two 2-hydroxypyridine non
      labile ligands is found to be most active against the three cell lines.
      Variations in activity of TH5, TH6 and TH7 indicate that non-covalent
      interactions may be playing a significant role in activity. In particular, the
      results indicate that small changes in planaramine ligands such as the position
      of the polar OH group can have a more profound effect on activity of the
      compounds. Palladium compounds are generally found to be toxic rather tumour
      active because of much higher reactivity. Low but significant activity of trans
      palladium(II) complexes TH5, TH6 and TH7 against the ovarian cancer cell lines
      indicates that it is believed to be associated with the decrease in their
      reactivity due to the presence of two sterically hindered planaramine ligands.

PMID- 16997378
TI  - Human papillomavirus and circumcision: a meta-analysis.
AB  - BACKGROUND: Determine the relationship of circumcision status to the risk for
      genital infection with human papillomavirus (HPV). METHODS: A MEDLINE search and
      a review of references in published articles were used to identify publications
      from peer-reviewed journals in Index Medicus with data on circumcision status in
      patients with and without HPV infections. Inclusion criteria included diagnosis
      by culture, biopsy, or PCR, determination of circumcision status by physical
      examination, and multiple site sampling including the shaft of the penis. A meta
      analysis was performed with sensitivity analyses. RESULTS: Sixteen articles
      contained data on circumcision status in patients with and without HPV
      infections. Eight studies used accurate diagnostic methods. Only three articles
      satisfied the strict inclusion criteria. There was no significant association
      between circumcision status and HPV infection (random-effects model summary
      effect OR=1.20, 95%CI=0.80-1.79) in these three studies. If the eight studies
      using accurate diagnostic methods are adjusted for the method of determining
      circumcision status and failure to sample the penile shaft using meta-regression
      the summary effects odds ratio is 1.25 (95%CI=0.95-1.67). CONCLUSIONS: The
      medical literature does not support the claim that circumcision reduces the risk
      for genital HPV infection. To correctly assess the risk of HPV infection in
      circumcised males, the penile shaft needs to be sampled for HPV infection.

PMID- 16997379
TI  - Precore and core promoter mutations at the time of HBeAg seroclearance in Chinese
      patients with chronic hepatitis B.
AB  - OBJECTIVE: To determine the prevalence of precore and core promoter (CP)
      mutations before, at and after HBeAg seroclearance in Chinese patients. METHODS:
      Precore and CP mutations were determined in 93 patients with chronic hepatitis B
      12-24 months before, at and 12 months after the time of HBeAg seroclearance.
      RESULTS: No significant changes were found in the prevalence of precore or CP
      mutations before, at and after HBeAg seroclearance. Seven patients (7.8%) had
      HBeAg seroreversion within 1 year of HBeAg seroclearance. There was no
      significant difference in the prevalence of precore and CP mutations between
      patients with and without HBeAg seroreversion. 68.3% and 48.7% of patients
      harbored the same precore and CP genotypes throughout. 32.0% patients with
      precore mutations and 8.9% patients with CP mutations before HBeAg seroclearance
      had reversion to wild type within 1 year of HBeAg seroclearance. Patients with
      genotype C patients had a higher prevalence of CP mutations before HBeAg
      seroclearance compared with patients with genotype B (82.4% vs. 44%, P=0.001).
      CONCLUSIONS: Precore and CP mutations existed in a substantial proportion of
      Chinese patients before HBeAg seroclearance. The replication of precore and, to a
      lesser extent, CP mutants could be suppressed around the time of HBeAg
      seroclearance.

PMID- 16997380
TI  - Using double-magnetic induction to measure head-unrestrained gaze shifts. I.
      Theory and validation.
AB  - So far, the double-magnetic induction (DMI) method has been successfully applied
      to record eye movements from head-restrained humans, monkeys and cats. An
      advantage of the DMI method, compared to the more widely used scleral search coil
      technique, is the absence of vulnerable lead wires on the eye. A disadvantage,
      however, is that the relationship between the eye-in-head orientation and the
      secondary induction signal is highly non-linear and non-monotonic. This limits
      the effective measuring range to maximum eye orientations of about +/-30 degrees
      . Here, we analyze and test two extensions required to record the full eye-head
      orienting range, well exceeding 90 degrees from straight-ahead in all directions.
      (1) The use of mutually perpendicular magnetic fields allows for the
      disambiguation of the non-monotonic signal from the ring. (2) The application of
      an artificial neural network for offline calibration of the signals. The
      theoretical predictions are tested for horizontal rotations with a gimbal system.
      Our results show that the method is a promising alternative to the search coil
      technique.

PMID- 16997381
TI  - Endogenous and exogenous cyclicity and temperament in bipolar disorder: review,
      new data and hypotheses.
AB  - In this special issue dedicated to Falret and the French contributions to the
      concept of cyclicity in manic depressive illness, we begin with a historical
      overview of the development of the concept of cyclicity and its fundamental
      significance in manic-depressive illness and we underscore how the concept fell
      into neglect only to reemerge in recent years. We then look at the intimate
      relationship between mania and depression. The hypothesis of the primacy of mania
      is discussed. The thesis is presented, supported by the examination of 100
      consecutive index manias, that in most cases mania is triggered by external
      factors acting upon hyperthymic patients, determining an exogenous cyclicity. On
      the other hand, in BPII patients the temperamental mood instability (cyclothymia)
      is an inherent and decisive factor in determining the cyclic autonomous course of
      the disorder. Finally, a new distinction of Bipolar Disorders, based on premorbid
      temperament and course of the illness, is considered.

PMID- 16997382
TI  - The neurobiology and clinical significance of depersonalization in mood and
      anxiety disorders: a critical reappraisal.
AB  - Depersonalization and derealization occur on a continuum of situations, from
      healthy individuals to a severely debilitating disorder where the symptoms can
      persist chronically. Since 1960s, different neurobiological models have been
      hypothesized and they have been associated with the temporal lobes. Recent
      advances in the functioning of the limbic system and the application of
      Geschwind's concept of disconnection in the cortico-limbic networks, pointed the
      role of the amygdala and its connections with medial prefrontal cortex and
      anterior cingulate cortex, the same structures that are strictly interlinked with
      the neurobiology of emotions and affective disorders. In this paper, we
      hypothesize that depersonalization may represent a clinical index of disease
      severity, poorer response to treatment and high level of comorbidity, in mood and
      anxiety disorders, discussing the neurobiology of depersonalization and the
      available clinical evidence.

PMID- 16997384
TI  - Vaccination of bovines with recombinant Boophilus Yolk pro-Cathepsin.
AB  - Boophilus Yolk pro-Cathepsin (BYC) is an aspartic proteinase found in Boophilus
      microplus eggs that is involved in the embryogenesis and has been tested as
      antigen to compose an anti-tick vaccine. The vaccine potential of a recombinant
      BYC expressed in Escherichia coli (rBYC) was investigated. rBYC was purified and
      used to immunize Hereford cattle. The sera of bovines immunized with rBYC
      recognized the native BYC with a titer ranging from 125 to 4000. Furthermore,
      immunized bovines challenged with 20,000 larvae presented an overall protection
      of 25.24%. The partial protection obtained against B. microplus infestation with
      the recombinant protein immunization was similar to the already described for
      native BYC immunization.

PMID- 16997383
TI  - Validity of the assessment of bipolar spectrum disorders in the WHO CIDI 3.0.
AB  - OBJECTIVE: Although growing interest exists in the bipolar spectrum, fully
      structured diagnostic interviews might not accurately assess bipolar spectrum
      disorders. A validity study was carried out for diagnoses of threshold and sub
      threshold bipolar disorders (BPD) based on the WHO Composite International
      Diagnostic Interview (CIDI) in the National Comorbidity Survey Replication (NCS
      R). CIDI BPD screening scales were also evaluated. METHOD: The NCS-R is a
      nationally representative US household population survey (n=9282 using CIDI to
      assess DSM-IV disorders. CIDI diagnoses were evaluated in blinded clinical
      reappraisal interviews using the non-patient version of the Structured Clinical
      Interview for DSM-IV (SCID). RESULTS: Excellent CIDI-SCID concordance was found
      for lifetime BP-I (AUC=.99 kappa=.88, PPV=.79, NPV=1.0), either BP-II or sub
      threshold BPD (AUC=.96, kappa=.88, PPV=.85, NPV=.99), and overall bipolar
      spectrum disorders (i.e., BP-I/II or sub-threshold BPD; AUC=.99, kappa=.94,
      PPV=.88, NPV=1.0). Concordance was lower for BP-II (AUC=.83, kappa=.50, PPV=.41,
      NPV=.99) and sub-threshold BPD (AUC=.73, kappa=.51, PPV=.58, NPV=.99). The CIDI
      was unbiased compared to the SCID, yielding a lifetime bipolar spectrum disorders
      prevalence estimate of 4.4%. Brief CIDI-based screening scales detected 67-96% of
      true cases with positive predictive value of 31-52%. LIMITATION: CIDI prevalence
      estimates are still probably conservative, though, but might be improved with
      future CIDI revisions based on new methodological studies with a clinical
      assessment more sensitive than the SCID to sub-threshold BPD. CONCLUSIONS:
      Bipolar spectrum disorders are much more prevalent than previously realized. The
      CIDI is capable of generating conservative diagnoses of both threshold and sub
      threshold BPD. Short CIDI-based scales are useful screens for BPD.

PMID- 16997386
TI  - Higher brain functions of GJB2-associated deafness.

PMID- 16997385
TI  - Pulse-oximetery is useful in determining the indications for adeno-tonsillectomy
      in pediatric sleep-disordered breathing.
AB  - OBJECTIVE: Although first line therapy of sleep-disordered breathing (SDB) in
      children is adeno-tonsillectomy, the indications for this operation have not yet
      been clearly established. We investigated whether pulse-oximetry is useful for
      determining the optional treatment modality for pediatric SDB. METHOD: Two
      hundred and thirty-two children presenting with snoring and gasping had their
      oxygen saturation levels examined during sleep. Among them, 86 underwent on adeno
      tonsillectomy and were evaluated pre- and post-surgery. We also examined 25
      healthy children as controls. RESULTS: Little desaturation was observed in
      healthy children. The difference in oxygen saturation levels of the patients
      between pre- and post-surgery was closely correlated with the pre-surgery levels.
      We examined the reaction operation characteristics and concluded that children
      with an oxygen desaturation index of 4% or more (ODI4) of more than 1.5 and/or
      ODI3 of more than 3.5 should undergo surgery. CONCLUSION: Pulse-oximetry is
      useful in determining the indications for adeno-tonsillectomy.

PMID- 16997387
TI  - The ages of suspicion, diagnosis, amplification, and intervention in deaf
      children.
AB  - OBJECTIVES: The present study sought to determine the average ages of suspicion,
      diagnosis, and amplification of profound hearing loss and intervention in deaf
      children and to compare at-risk and not-at-risk children based on the studied
      ages. METHODS: This study was conducted on 86 children under 6 years of age with
      profound bilateral hearing loss in Newsha Aural Rehabilitation Center in Tehran
      from July to December 2005. Data were gathered through the completion of a
      questionnaire by the children's parents, and the children's medical and
      rehabilitative records were utilized in order to determine the kind and degree of
      hearing loss. RESULTS: The mean ages of suspicion, diagnosis, amplification, and
      intervention were 12.6+/-8.9, 15.2+/-9.3, 20.5+/-11.1, and 22.3+/-11.6 months,
      respectively; there being statistically significant differences between them.
      47.7% of the children were in the high-risk group, and statistically there were
      no significant differences between the at-risk and not-at-risk children in the
      studied ages. Of all the neonatal diseases investigated, hyperbilirubinemia was
      the most frequent (40.7%), and there were also four cases of meningitis and six
      cases of measles. In terms of consanguinity, mating of first cousins was 41.9%
      and mating of second cousins and farther familial relationships was 14%. After
      suspecting hearing loss in their children, the parents had visited physicians
      (57%), audiologists (37.2%), speech therapists (2.3%), or other specialists
      (3.5%) for the first time. The economic circumstances of the families had a
      significant bearing on the average ages of suspicion, diagnosis, amplification,
      and intervention. CONCLUSIONS: Despite the remarkable improvement in the average
      ages of suspicion, diagnosis, amplification, and intervention in comparison with
      those reported in a previous study carried out in Iran (2002), there is still
      noticeable difference between these ages and those suggested by the Joint
      Committee on Infant Hearing.

PMID- 16997388
TI  - Preclinical research into cognition enhancers.
AB  - The preclinical development of drugs to treat the cognitive symptoms of
      neuropsychiatric and neurological disorders is a formidable challenge. Evidence
      from a wide range of preclinical behavioral and neuropharmacological tests has
      formed the basis for predicting drug-induced cognition enhancement in normal
      volunteers and in patients with cognitive impairments. However, the limited
      validity of preclinical predictions of this enhancement in humans indicates that
      conventional screening for "broadly active" compounds represents a below-optimal
      research strategy. This article conceptualizes the evidence needed to improve the
      predictive validity of preclinical research designed to discover and characterize
      cognition enhancers. We suggest that the investigation of reciprocal
      relationships among molecular, cellular, behavioral and cognitive processes
      modulated by candidate drugs represents the core of such research. By contrast,
      the usefulness of simple and high-throughput screening tests for the detection of
      cognition enhancers might be restricted to advanced drug-finding programs that
      are guided by evidence of the modulation of neurocognitive relationships by
      cognition enhancers and that are informed by iterative preclinical-clinical cross
      validation of research approaches. We stress the need for basic biopsychological
      research approaches in preclinical programs to find and characterize drugs to
      treat cognitive disorders.

PMID- 16997389
TI  - Development of real-time RT-PCR methods for specific detection of F-specific RNA
      bacteriophage genogroups: application to urban raw wastewater.
AB  - F-specific RNA bacteriophages have been classified into four genogroups (GI, GII,
      GIII and GIV). It was suggested that two of these genogroups are more frequent in
      human excreta (GII and GIII) and the two other (GI and GIV) are specific for
      animal excreta. Real-time RT-PCR methods using TaqMan MGB probe were developed to
      detect the four genogroups. Primers and probes of each specific RT-PCR were
      designed to target all sequenced bacteriophages belonging to one genogroup,
      without cross-reactivity with other genogroups. These four methods showed
      detection limits ranging between 0.01 and 10 PFU/mL and PCR efficiencies ranging
      between 87 and 95%. The newly methods were tested in urban raw wastewater.
      Genogroups I and II were detected in all samples (n=7); GIII in six samples and
      GIV was never detected. GI was predominant in one sample, in which the quantity
      of Cryptosporidium and Giardia was, respectively, three and eight times higher
      than the mean values. Because GI is mainly observed in animals, it was
      hypothesized that this increase was due to an animal input. The use of F-specific
      RNA phage genotyping to estimate the origin of faecal pollution requires
      appropriate validation. In this context, real-time RT-PCR will undoubtedly be
      useful.

PMID- 16997390
TI  - Natural killer cell inhibits human immunodeficiency virus replication in
      chronically infected immune cells.
AB  - Natural killer (NK) cells are a crucial component of the host innate immune
      system. We investigated the noncytolytic anti-human immunodeficiency virus (HIV)
      activity of NK cells in chronically HIV-infected immune cells. Supernatants
      collected from NK cell cultures (both primary NK cells and NK cell lines, YTS and
      NK 92) inhibited HIV activation in peripheral blood mononuclear cells (PBMCs)
      from HIV-infected subjects. NK supernatants (NK SN) also suppressed tumor
      necrosis factor (TNF)-alpha-induced HIV activation in chronically infected cell
      lines (U1 and ACH-2 cells). The antibody to interferon (IFN)-gamma blocked NK SN
      mediated anti-HIV effect, while the antibodies to CC-chemokines had no impact on
      NK SN-mediated HIV inhibition in U1 and ACH-2 cells. Investigation of
      mechanism(s) responsible for the NK action showed that NK SN inhibited TNF-alpha
      mediated activation of HIV-long-terminal repeat (LTR), and upregulated the
      expression of signal transducer and activator of transcription (STAT)-1 and
      phosphorylated P38 mitogen-activated protein kinase (MAPK). The P38 MAPK
      inhibitor (SB 203580) blocked NK SN-mediated HIV inhibition. These data provide
      compelling evidence that NK cells have a critical role in controlling HIV
      activation in the reservoirs.

PMID- 16997391
TI  - Elevated pCREB in the PAG after exposure to the elevated plus maze in rats
      previously exposed to a cat.
AB  - The elevated plus maze (EPM) is an ethologically based test of anxiety-like
      behavior. In addition, exposure to the maze itself is stressful and anxiogenic.
      One of the goals of this study was to examine if the stress of EPM exposure
      increased pCREB-like-immunoreactivity (lir). The second goal of this study was to
      determine if prior stress impacted expression of pCREB-lir in animals exposed to
      the EPM. Toward this end, pCREB-lir was examined after exposure to the EPM in
      young adult male rats that had been exposed to a cat 7 days earlier. Brain areas
      investigated included the amygdala, periaqueductal gray (PAG), and bed nucleus of
      the stria terminalis (BNST), all areas considered to be part of the "fear
      circuit". Results show that there were no pCREB-lir differences between control
      rats and rats exposed to the EPM only. However, exposure to the EPM in predator
      stressed rats showed elevated pCREB-lir in the right lateral column of the PAG
      and bilaterally in the dorsal column of the PAG. In contrast, EPM exposure did
      not elevate pCREB-lir in the amygdala or BNST in predator stressed rats. Findings
      suggest mechanisms associated with neuroplasticity may be engaged by relatively
      mild stresses in animals with a history of severe stress exposure. This may be
      clinically relevant, as a key feature of posttraumatic stress disorder (PTSD) is
      the exaggerated reaction to a mild stressor in which the response is more
      appropriate to the original traumatic situation than the current conditions. If
      what happens in animals also occurs in humans, the findings of this study suggest
      that neural mechanisms of prior traumatic stress may interact with subsequent
      stress to reinforce psychopathology.

PMID- 16997393
TI  - Quantitative studies on the effects of environmental estrogens on the testis of
      the guppy, Poecilia reticulata.
AB  - Estrogens that enter into the water system, such as by sewage effluent, may
      affect the reproductive capabilities of aquatic animals. The guppy (Poecilia
      reticulata) was chosen as a model organism to test the level of disturbances in
      primary and secondary sexual characteristics. Male guppies were exposed to 17beta
      estradiol (10 and 50 ng L(-1)), and 17alpha-ethinylestradiol (10, 50 and 200 ng
      L(-1)) for 3.5 months from birth to adulthood. Specimens were euthanized and the
      testes removed for histological examination, applied in conjunction with
      stereological technique. Alterations in the quantity of sperm, decreasing
      intensity of body coloration, and increased body weight were generally
      significant only in the group exposed to 200 ng L(-1) of 17alpha
      ethinylestradiol. No significant changes were seen in the gonadosomal index
      (GSI). Quantification of the developmental stages of spermatogenesis indicated a
      trend of greater representation of later stages in specimens exposed to low doses
      of estrogens, and greater prevalence of early stages in those exposed to high
      doses of estrogens. Based on the results of this study, environmental estrogens
      do not seem to pose a reproductive threat to guppies. It is concluded that
      stereological histology can be considered a valuable tool in quantifying
      estrogenic effects upon fish gonads and that the guppy is perhaps not an ideal
      test organism for estrogenic exposure due to limited sensitivity.

PMID- 16997392
TI  - Animal models of restricted repetitive behavior in autism.
AB  - Restricted, repetitive behavior, along with deficits in social reciprocity and
      communication, is diagnostic of autism. Animal models relevant to this domain
      generally fall into three classes: repetitive behavior associated with targeted
      insults to the CNS; repetitive behavior induced by pharmacological agents; and
      repetitive behavior associated with restricted environments and experience. The
      extant literature provides potential models of the repetitive behavioral
      phenotype in autism rather than attempts to model the etiology or pathophysiology
      of restricted, repetitive behavior, as these are poorly understood. This review
      focuses on our work with deer mice which exhibit repetitive behaviors associated
      with environmental restriction. Repetitive behaviors are the most common category
      of abnormal behavior observed in confined animals and larger, more complex
      environments substantially reduce the development and expression of such
      behavior. Studies with this model, including environmental enrichment effects,
      suggest alterations in cortical-basal ganglia circuitry in the development and
      expression of repetitive behavior. Considerably more work needs to be done in
      this area, particularly in modeling the development of aberrant repetitive
      behavior. As mutant mouse models continue to proliferate, there should be a
      number of promising genetic models to pursue.

PMID- 16997395
TI  - ATM activation is accompanied with earlier stages of prostate tumorigenesis.
AB  - The ATM (ataxia telangiectasia mutated) kinase plays an essential role in
      maintaining genome integrity by coordinating cell cycle arrest, apoptosis, and
      DNA damage repair. Phosphorylation of ATM at serine 1981 (ATMpSer1981) by DNA
      damage activates ATM, which subsequently phosphorylates H2AX Ser139 (gammaH2AX),
      Chk2 Thr68 (Chk2pThr68), and p53 Ser15 (p53pSer15). To determine the role of the
      ATM pathway in prostate cancer tumorigenesis, we have analyzed 35 primary
      prostate cancer specimens for ATMpSer1981 (ATM activation), Chk2pThr68,
      gammaH2AX, and p53pSer15 by immunohistochemistry (IHC) in normal glands,
      prostatic intraepithelial neoplasias (PINs), and carcinomas. Increases in the
      intensities of ATMpSer1981, Chk2pThr68, and gammaH2AX and in the percentage of
      cells that are positive for ATMpSer1981, Chk2pThr68, or gammaH2AX were observed
      in PINs (p<0.001) compared to normal prostatic glands and carcinoma. However,
      this pattern of immunostaining was not seen for p53pSer15. Thus, ATM and Chk2 are
      specifically activated in PINs. As PINs are generally regarded as precursors of
      prostatic carcinoma, our results suggest that ATM and Chk2 activation at earlier
      stages of prostate tumorigenesis suppresses tumor progression, with attenuation
      of ATM activation leading to cancer progression.

PMID- 16997394
TI  - HNF4alpha and NF-E2 are key transcriptional regulators of the murine Abcc6 gene
      expression.
AB  - Mutations in an ABC transporter gene called ABCC6 are responsible for
      pseudoxanthoma elasticum (PXE), a rare heritable disease characterized by elastic
      fiber calcification in skin, ocular and vascular tissues. The presumed function
      of this ABC transporter is to export metabolites from polarized cells. However,
      the endogenous substrate(s) are unknown and the exact relationship with elastic
      fibers is unclear. As ABCC6 is only expressed at high level in liver and kidneys,
      tissues seemingly unrelated to the PXE phenotype, we explored the transcriptional
      regulation of the murine Abcc6 gene to define the transcriptional signal
      conferring tissue specificity and to gather clues on its possible biological
      function. We cloned 2.9 kb of the mAbcc6 5'-flanking region and several deletion
      constructs linked to a luciferase reporter gene. We delineated a proximal
      promoter and a liver-specific enhancer region. We also demonstrated that the
      proximal region is a TATA-less promoter requiring an intact CCAAT-box and Sp1
      binding for its basal activity. By using reporter assays and chromatin
      immunoprecipitations, we showed that HNF4alpha and surprisingly, NF-E2, enhanced
      the mAbcc6 promoter activity. The involvement of both HNF4alpha and NF-E2 in the
      mAbcc6 gene regulation suggests that Abcc6 might be involved in a detoxification
      processes related to hemoglobin or heme.

PMID- 16997397
TI  - Contribution of falling and being homebound status to subsequent functional
      changes among the Japanese elderly living in a community.
AB  - Using the data from the community-based longitudinal study of the elderly persons
      aged 65 or older, this study examined relationships between the occurrence of
      falls varied by their activity level and subsequent functional decline over time.
      Of the 705 respondents at baseline, 662 and 632 subjects were assessed at first
      and second follow-ups. Falling and homebound status at baseline and health
      function (self-rated general health, activities of daily living (ADLs),
      instrumental activities of daily living (IADLs), intellectual activity, and
      social role) at baseline and follow-ups were assessed, and changes in each health
      function were compared among four groups defined by baseline falling/homebound
      status. Baseline falling/homebound status was significantly associated with
      subsequent decline in ADLs over 1 year, and in ADLs, IADLs, intellectual
      activity, and social role over 2 years. Being homebound might act as a stronger
      risk factor for ADLs disabilities rather than the occurrence of falls. Moreover,
      the homebound elderly with no experience of falls was at the greatest risk of the
      decline of social role. We consider that prevention program and home-based care
      for homebound elderly should be provided in the community.

PMID- 16997396
TI  - CRM 1-mediated degradation and agonist-induced down-regulation of beta-adrenergic
      receptor mRNAs.
AB  - The beta1-adrenergic receptor (beta1-AR) mRNAs are post-transcriptionally
      regulated at the level of mRNA stability and undergo accelerated agonist-mediated
      degradation via interaction of its 3' untranslated region (UTR) with RNA binding
      proteins, including the HuR nuclear protein. In a previous report [Kirigiti et
      al. (2001). Mol. Pharmacol. 60:1308-1324], we examined the agonist-mediated down
      regulation of the rat beta1-AR mRNAs, endogenously expressed in the rat C6 cell
      line and ectopically expressed in transfectant hamster DDT1MF2 and rat L6 cells.
      In this report, we determined that isoproterenol treatment of neonatal rat
      cortical neurons, an important cell type expressing beta1-ARs in the brain,
      results in significant decreases in beta1-AR mRNA stability, while treatment with
      leptomycin B, an inhibitor of the nuclear export receptor CRM 1, results in
      significant increases in beta1-AR mRNA stability and nuclear retention. UV
      crosslinking/immunoprecipitation and glycerol gradient fractionation analyses
      indicate that the beta1-AR 3' UTR recognize complexes composed of HuR and
      multiple proteins, including CRM 1. Cell-permeable peptides containing the
      leucine-rich nuclear export signal (NES) were used as inhibitors of CRM 1
      mediated nuclear export. When DDT1MF2 transfectants were treated with
      isoproterenol and peptide inhibitors, only the co-addition of the NES inhibitor
      reversed the isoproterenol-induced reduction of beta1-AR mRNA levels. Our results
      suggest that CRM 1-dependent NES-mediated mechanisms influence the degradation
      and agonist-mediated down-regulation of the beta1-AR mRNAs.

PMID- 16997398
TI  - Diagnostic accuracy of serum B-type natriuretic peptide for myocardial ischemia
      detection during exercise testing with spect perfusion imaging.
AB  - OBJECTIVE: To determine whether serum B-type natriuretic peptide measured at rest
      and peak exercise and DeltaBNP contribute to the predictive value and diagnostic
      accuracy of exercise test in the diagnosis of myocardial ischemia. BACKGROUND:
      Ventricular myocytes release BNP in response to increased wall stress that occurs
      in acute ischemia. During exercise testing, transient myocardial ischemia could
      also cause acute myocardial stress and changes in circulating BNP. METHODS: BNP
      was measured before and immediately after exercise testing with radionuclide
      imaging in 203 consecutive subjects referred for chest pain evaluation. Tested
      subjects were classified as ischemic and non-ischemic based on exercise results,
      and no ischemia, mild-moderate, and severe ischemia according to perfusion scan
      results. A logistic regression model, constructed of an ROC and an AUC (area
      under the curve), was used. RESULTS: Ischemic ECG changes (> or =1 mm, horizontal
      S-T shift) were detected in the treadmill exercise test in 127 subjects (62.6%),
      and 76 (37.4%) had neither ST segment shift nor chest pain. Baseline BNP was
      higher in the ischemic group compared to the non-ischemic group (p=0.044); peak
      BNP was also higher in the ischemic group (p=0.025), as was DeltaBNP (p=0.0126).
      Of these 127 subjects, 106 (52% of all) had abnormal perfusion scan results. In
      the ischemic group, the median baseline, peak exercise BNP, and DeltaBNP values
      from baseline to peak were higher than in the non-ischemic group. In the severe
      ischemic group these variables were approximately three-fold higher than in the
      mild-moderate ischemic group (p<0.0001 for baseline; p<0.0001 for peak; and
      p<0.0001 for DeltaBNP). Rest, peak exercise, and DeltaBNP values were
      significantly higher in patients with previous myocardial infarction (p<0.001)
      and in patients treated with beta blockers; peak exercise BNP was higher in
      hypertensives and diabetics (p<0.05). The ROC convergence model showed that the
      AUC for peak-exercise BNP was best able to discriminate and predict severe
      ischemia and no ischemia, while DeltaBNP from rest to peak exercise discriminated
      best between mild-moderate and severe ischemia. CONCLUSIONS: Peak exercise BNP
      and DeltaBNP improved the sensitivity, specificity, positive likelihood ratio,
      predictive value, and diagnostic accuracy of severe ischemia detection during an
      exercise test. The contribution of BNP determination during exercise was,
      however, less impressive than previously reported by others.

PMID- 16997399
TI  - Occult cardiac dysfunction in patients with obstructive sleep apnea syndrome
      revealed by tissue Doppler imaging.
AB  - Obstructive sleep apnea syndrome has been linked to cardiovascular complications.
      The diagnosis of effects of sleep apnea on heart may be difficult before apparent
      examination findings. The aim of the present study was to evaluate changes of
      myocardial contractile properties in patients affected by sleep apnea showing
      tissue Doppler imaging, in the face of quite normal myocardial contractility on
      standard echocardiography. Shortly, tissue Doppler imaging may represent an early
      stage of myocardial abnormality despite a preserved global function.

PMID- 16997400
TI  - Radiation exposure during follow-up of adults with congenital heart disease.
AB  - BACKGROUND: Adult patients with congenital heart disease under follow-up often
      need to undergo diagnostic procedures which expose them to radiation. AIM: To
      evaluate radiation doses in adult patients with congenital heart disease during
      follow-up. METHODS: Data on diagnostic procedures were used from the European
      Heart Survey on adult congenital heart disease, a multicenter retrospective
      cohort study. Lesions included in the survey were Atrial Septal Defect,
      Ventricular Septal Defect, Fallot, Fontan, Coarctation, Transposition of the
      Great Arteries, Marfan, and Cyanotic lesions. A total of 4110 patients (52%
      female) with a mean age of 32 years (range 17-85) were included. The follow-up
      time ranged from 0 to 72 months, with a median of 61 months. There were a total
      of 18,403 patient-years of follow-up. During this time, a mean of 4.5 visits per
      patient took place. Radiation doses were calculated using the number of
      examinations in each patient's data file. Effective radiation doses are given in
      millisievert (mSv). RESULTS: The average cumulative annual effective dose per
      patient was 0.46 mSv. The relative contributions to these doses were 3% by chest
      X-rays, 39% by computed tomography scans, 42% by angiography, and 16% by nuclear
      scans. Effective doses were higher in patients with Fontan, Coarctation, Marfan
      and Cyanotic lesions, as well as in patients with Atrial Septal Defects.
      CONCLUSIONS: Exposure to radiation during follow-up of patients with adult
      congenital heart disease mainly stems from computed tomography scans and
      angiography. Patients with Fontan, Coarctation, Marfan and Cyanotic lesions are
      more likely to get high doses from computed tomography. In these lesions,
      therefore, particular care should be taken to use non-ionizing imaging procedures
      whenever possible.

PMID- 16997401
TI  - Nitric oxide-releasing aspirin: will it say NO to atherothrombosis?
AB  - Aspirin is a powerful anti-platelet drug widely used in patients with coronary
      atherosclerosis, but its side effects and especially its toxicity for
      gastrointestinal tract limit its usefulness in specific groups of patients. A new
      category of agents, nitric oxide-releasing aspirins (such as NCX-4016), seems to
      provide an alternative solution. Although this drug is still at phase II clinical
      trials, it has provided promising results until now. When administered in vivo,
      it is separated into an aspirin moiety and an NO-donating complex, providing both
      the antithrombotic effect of aspirin and the gastroprotective effect of NO.
      Additionally, it increases NO bioavailability as a vascular level, and it may
      have the antiatherogenic properties of endogenously produced NO. Finally, recent
      evidence suggests that it may also improve functional aspects of vein grafts used
      in CABG, with possible benefit on graft patency. However, the outcome of the
      large ongoing trials is needed before any conclusion is made about the role of NO
      releasing aspirins in cardiovascular disease.

PMID- 16997402
TI  - Renal dysfunction is an independent predictor of in-hospital mortality in
      patients with ST-segment elevation myocardial infarction treated with primary
      angioplasty.
AB  - BACKGROUND: Patients with baseline renal dysfunction (BRD) have an increased
      cardiovascular risk and a worse prognosis after an acute myocardial infarction
      (AMI). Besides, the appearance of worsening renal failure (WRF) after an AMI is
      an independent predictor of worse prognosis too. The aim of the present study was
      to determine the in-hospital prognostic significance of BRD and WRF in patients
      with ST-segment elevation myocardial infarction (STEMI) who underwent successful
      primary angioplasty (PA). METHODS: Seventy-six consecutive patients with STEMI
      diagnosis were admitted to our department and treated with PA successfully. Two
      groups were established in relation to the presence of BRD on admission (defined
      by a ClCr<60 ml/min/1.73 m2, estimated by the modification of diet in renal
      disease equation). We compared their baseline characteristics and their in
      hospital mortality and developing of WRF. RESULTS: BRD was associated to a
      greater in-hospital mortality (11.5% vs. 2.7%, p=0.009) and a higher incidence of
      WRF (12.2% vs. 2.5%, p<0.001). After adjusting by confounding factors, the
      multiple logistic regression analysis demonstrated that BRD was an independent
      predictor of in-hospital mortality (OR 2.5, CI 95% 1.5-3.8, p<0.001). Besides,
      WRF was associated to a greater in-hospital mortality too, independent of the
      presence of BRD (OR 1.9, CI 95% 1.3-2.4, p<0.001). CONCLUSIONS: BRD was an
      independent predictor of in-hospital mortality in patients with STEMI who
      underwent successful PA. Likewise, WRF occurring in these patients was an
      independent predictor of in-hospital mortality too.

PMID- 16997403
TI  - Quantification of the contact structure in a feral cattle population and its
      hypothetical effect on the transmission of bovine herpesvirus 1.
AB  - The organisation of animal populations in social groupings may play a crucial
      role in the transmission of any infectious disease that requires close contact.
      The objective of this study was to quantify the contact structure of part of the
      Heck cattle population in a Dutch nature reserve and its hypothetical effect on
      the transmission of bovine herpesvirus 1 (BHV1). The contact structure was
      quantified by observing the number of different animals with whom contact was
      made (i.e. the number of contactees) within a fixed time period. Two types of
      behaviour sampling methods, namely focal sampling and scan sampling were used to
      observe the contact structure. In this study only those contacts between
      individuals were observed that were assumed to be a proxy measure of an at-risk
      event for BHV1-infection. Two reproduction ratios (R), i.e. the average number of
      new cases caused by a typical infected individual, were estimated, one for the
      observed contact structure and another for a random mixing contact structure. The
      two reproduction ratios were then compared to study the hypothetical effect on
      BHV1 transmission. The overall number of contactees was highest during summer and
      lowest during winter-spring. The contact structure of the homogeneous population
      did differ significantly from a random mixing contact structure, resulting in
      that the variation in the number of contactees was higher than under random
      mixing. Bulls, young bulls and cows had the highest number of contactees during,
      respectively, summer, autumn and winter-spring. From the analysis of the
      contingency tables it was clear that contacts between animal types did not occur
      at random during summer and autumn. For example, during summer more contacts than
      expected occurred between bulls and cows. This heterogeneity at animal type level
      was taken into account in the calculation for R, which resulted for the observed
      contact structure in higher estimates for R than for the homogeneous population.
      When looking at heterogeneity at individual level it was found that during summer
      almost all individuals were observed together direct or indirect in the same
      group except for certain bull groups. During autumn and winter-spring almost all
      individuals were seen together in the same group when considering a long contact
      period of 14 days but the groups were fallen apart in smaller groups and solitary
      individuals for a short contact period of 5 days. It could be concluded that
      based on the observed contact structure transmission would be favoured most
      during summer.

PMID- 16997404
TI  - Clonal isolation of chlamydia-infected cells using flow cytometry.
AB  - This manuscript describes a new technique for the microbiological cloning of
      chlamydia-infected cells using a fluorescence activated cell sorter (FACS). The
      approach exploits chlamydial acquisition of the fluorescent, Golgi-specific,
      stain 6-((N-7-(-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-hexanoyl)sphingosine (C6
      NBD-cer). This fluorescent lipid is delivered from the Golgi apparatus to the
      chlamydial inclusion membrane and then to the developmental forms within the
      inclusion in living, infected cells. Labeling with C6-NBD-cer results in easily
      identifiable chlamydial inclusions that can then be analyzed and sorted by FACS.
      This technique was used successfully to sort individual chlamydia-infected cells
      into individual wells of a culture dish and, in this experimental system,
      resulted in the isolation of cloned chlamydial isolates. FACS-based sorting was
      used to isolate clonal populations of prototype strains from Chlamydia
      trachomatis, C. caviae and C. suis. Recent clinical isolates were also
      successfully cloned using FACS. The procedure is simple and rapid, with single
      cloning cycles being completed 24 h post-culture of a sample. It is anticipated
      that FACS-based sorting of live chlamydia-infected cells will be a significant
      technical tool for the isolation of clonal populations of any chlamydial strain.

PMID- 16997405
TI  - Towards commercial production of microbial surfactants.
AB  - Biosurfactants or microbial surfactants are surface-active biomolecules that are
      produced by a variety of microorganisms. Biosurfactants have gained importance in
      the fields of enhanced oil recovery, environmental bioremediation, food
      processing and pharmaceuticals owing to their unique properties--higher
      biodegradability, lower toxicity, and effectiveness at extremes of temperature,
      pH and salinity. However, large-scale production of these molecules has not been
      realized because of low yields in production processes and high recovery and
      purification costs. This article describes some practical approaches that have
      been adopted to make the biosurfactant production process economically
      attractive: these include the use of cheaper raw materials, optimized and
      efficient bioprocesses and overproducing mutant and recombinant strains for
      obtaining maximum productivity. The application of these strategies in
      biosurfactant production processes, particularly those using hyper-producing
      recombinant strains in the optimally controlled environment of a bioreactor,
      might lead towards the successful commercial production of these valuable and
      versatile biomolecules in near future.

PMID- 16997406
TI  - Hybrid transcription-mediated transgene regulation in plastids.
AB  - Plastids are semi-autonomous plant organelles with their own transcription and
      translation machinery that are suitable for producing high levels of transgenic
      proteins with a bona fide structure. However, the transcription of endogenous
      plastid genes is largely dependent on nuclear-encoded transcription factors, and
      the identification of these factors has implications for transgene regulation. A
      novel transcription system has recently been reported that works independently of
      the plastid transcription machinery and is potentially useful for transgene
      containment and to express genes with the assurance of high-level protein
      accumulation.

PMID- 16997407
TI  - Theory of the normal waking EEG: from single neurones to waveforms in the alpha,
      beta and gamma frequency ranges.
AB  - The classic alpha rhythm, recorded intracortically, consists of alternating
      surface-negative troughs and briefer surface-positive peaks. The troughs are
      associated with neuronal hyperpolarization, the peaks with brief depolarization
      and burst firing. Each hyperpolarization is mainly a potassium potential, lasting
      approximately 100 ms. Depolarization and burst firing arise when this
      inactivates. In the desynchronized state, membrane potential is poised just below
      threshold. Firing in vivo is somewhat irregular and non-bursting. It is suggested
      that EEG bistability (classic alpha vs desynchronization) corresponds to
      bistability of single pyramidal cells. In vitro, paired pulses lead to depression
      of synaptic transmission in synapses linking two pyramidal cells, but to
      facilitation in synapses linking pyramidal cells to inhibitory neurones. These
      effects should be recruited by burst firing in vivo. Thus, enhancement of
      inhibitory and excitatory transmission occur respectively during the classic
      alpha rhythm, and the desynchronized state. As a result both states tend to be
      self-sustaining. In the desynchronized state high frequency (gamma or beta)
      activity predominates. In simulations, gamma activity has been modeled as the
      behaviour of cortical networks where populations of excitatory and inhibitory
      neurones interact. These simulations assume conduction times between neurones to
      be negligible. However, this is not true for long-distance interactions.
      Introduction into the models of plausible conduction delays should slow the
      oscillation frequency. The activated cortex can then produce not only gamma
      activity but also beta, and sometimes alpha activity. Thus, alpha frequencies can
      arise both in the "idling" cortex (classic alpha), and in the activated cortex,
      although the respective mechanisms are quite different.

PMID- 16997408
TI  - Therapeutic modulation of synaptic connectivity with desynchronizing brain
      stimulation.
AB  - In a modeling study, we show that synaptic connectivity can effectively be
      reshaped by an appropriate modulation of neuronal dynamics. To this end, we
      incorporate synaptic plasticity with symmetric spike-timing characteristics into
      a population of bursting neurons, which are interacting via chemical synapses.
      Under spontaneous conditions, qualitatively different stable dynamical states may
      coexist. We observe states characterized either by pathological synchrony or by
      uncorrelated activity. Suitably designed stimulation protocols enable to shift
      the neuronal population from one dynamical state to another. Due to low-frequency
      periodic pulse train stimulation, the population learns pathologically strong
      interactions, as known from the kindling phenomenon. In contrast, desynchronizing
      stimulation, e.g., multi-site coordinated reset stimulation, enables the network
      to unlearn pathologically strong synaptic interactions, so that a powerful long
      term anti-kindling is achieved. We demonstrate that anti-kindling can be achieved
      even with weak and/or short desynchronizing stimuli, which are not able to cause
      a complete desynchronization in the course of the stimulation. Our results show
      that desynchronizing stimulation may serve as a novel curative approach for the
      therapy of neurological diseases connected with pathological cerebral synchrony.

PMID- 16997409
TI  - Type II glucocorticoid receptor involvement in habituated activation of lateral
      hypothalamic area orexin-A-immunopositive neurons during recurring insulin
      induced hypoglycemia.
AB  - Neurons that synthesize the potent orexigenic neuropeptide, orexin-A (ORX-A) are
      confined to the lateral hypothalamic area (LHA) and adjacent structures, and
      project throughout the central neuroaxis to structures that govern central
      nervous system responses to energy imbalance. Insulin-induced hypoglycemia (IIH)
      upregulates prepro-orexin mRNA and Fos immunostaining of LHA ORX-A neurons. These
      neurons apparently become desensitized to this metabolic challenge, since both
      responses are diminished by recurrent insulin-induced hypoglycemia (RIIH). Recent
      studies implicate central type II glucocorticoid receptors (GR) in RIIH
      associated glucose counterregulatory collapse and decline in Fos labeling of
      central metabolic loci, including the LHA. The present studies evaluated the role
      of GR in patterns of LHA ORX-A neuronal transcriptional activation during RIIH.
      Groups of adult male rats were injected subcutaneously with one or four doses of
      the intermediate-acting insulin, Humulin NPH, on as many days, or with diluent
      alone. Rats injected with four doses of insulin were pretreated by
      intracerebroventricular (icv) administration of the selective GR antagonist, CP
      472555, or the vehicle, propylene glycol, prior to insulin administration on days
      1-3. All animals were sacrificed by transcardial perfusion 2h after injections on
      day 4. Processing of LHA tissue sections for dual-immunoperoxidase staining of
      ORX-A- and Fos-immunoreactivity (-ir) showed that colabeling of ORX-A neurons for
      Fos was increased by a single injection of NPH, whereas this genomic response was
      diminished by RIIH. Icv administration of CP-472555 during antecedent
      hypoglycemia prevented RIIH-associated reductions in Fos expression by these
      neurons. Antagonist treatment of diluent-injected controls did not alter mean
      numbers of ORX-A- plus Fos-ir neurons. Total numbers of ORX-A-immunopositive
      neurons were not different among treatment groups. These data demonstrate that
      precedent central GR blockade prevents adaptation of LHA ORX-A neuronal
      reactivity to RIIH. These results provide unique pharmacological evidence that
      hypoglycemic hypercorticosteronemia diminishes activation of this
      neurotransmitter phenotype in this critical metabolic structure to subsequent
      hypoglycemia via central GR-dependent mechanisms.

PMID- 16997410
TI  - Characterization of new bacteriocinogenic lactic acid bacteria isolated using a
      medium designed to simulate inhibition of Listeria by Lactobacillus sakei 2512 on
      meat.
AB  - Bacteriocinogenic bacteria have been proposed to protect food products from
      Listeria contamination as bioprotective cultures. Lactobacillus sakei 2512 was
      demonstrated to inhibit the growth of Listeria on sliced cooked ham by challenge
      test. A liquid medium simulating ham, BHI5L200, was designed in order to select
      bioprotective strains for meat protection. Two strains were selected, from the
      201 lactic acid bacteria screened, that produced bacteriocins at pH 5.8 in
      BHI5L200. The first one, Leuconostoc pseudomesenteroides 2733, produced a new
      bacteriocin which was purified and partially characterized. The second,
      Lactobacillus curvatus 2711, produced sakacin X and was shown to contain sakacin
      T and sakacin P structural genes. Co-culture experiments in BHI5L200 demonstrated
      that growth of Listeria was inhibited by L. sakei 2512 as well as by L. curvatus
      2711.

PMID- 16997411
TI  - Comparative analysis of a 3' end tag PCR and a linear RNA amplification approach
      for microarray analysis.
AB  - BACKGROUND: Various types of amplification techniques have been developed in
      order to enable microarray gene expression analysis when the amount of starting
      material is limited. The two main strategies are linear amplification, using in
      vitro transcription, and exponential amplification, based on PCR. We have
      evaluated the performance of a linear and an in-house developed exponential
      amplification protocol that relies on 3' end tag sequences. We used 100 ng total
      RNA as starting material for amplification and compared the results with data
      from hybridizations with unamplified mRNA and total RNA. RESULTS: Preservation of
      expression ratios after amplification was examined comparing log(2) ratios
      obtained with amplification protocols to those obtained with standard labelling
      of mRNA. The Pearson correlations were 0.61 and 0.84, respectively, for the two
      linear amplification replicates and 0.76 and 0.80 for the two exponential
      amplification replicates. The correlations between repeated amplifications was
      0.82 with the exponential method and 0.63 with the linear, indicating a better
      reproducibility with the PCR-based approach. CONCLUSION: Both amplification
      methods generated results in agreement with unamplified material. In this study,
      the PCR-based method was more reproducible than in vitro transcription
      amplification. Advantages with the in-house developed method are the lower cost
      since it is non-commercial and that the PCR generated product offers
      compatibility with both sense and antisense arrays.

PMID- 16997412
TI  - Puumala hantavirus in Slovenia: analyses of S and M segment sequences recovered
      from patients and rodents.
AB  - In Slovenia, the co-existence of Dobrava and Puumala (PUUV) hantaviruses in a
      single endemic region has been demonstrated. This study presents selected
      Slovenian HFRS cases caused by PUUV combined with genetic analysis of viral
      genome sequences recovered from clinical specimens and tissue samples of
      Clethrionomys glareolus (bank voles). Serum samples from nine HFRS patients were
      included in the study. Rodents study sites were selected with regard to the HFRS
      cases. Partial S segment sequences were recovered from all nine patients and
      partial M segment sequences could be recovered from seven. Partial S and M
      segments sequences were also recovered from five C. glareouls captured at three
      different study sites. The sequences from Slovenian clinical specimens and rodent
      tissue samples belonged to the PUUV genotype and formed a distinct genetic
      lineage of PUUV. Human and rodent PUUV sequences located in the closest proximity
      to each other on the phylogenetic trees suggest genetic links between the human
      cases and the hantaviral strains circulating in natural foci of this zoonotic
      infection. Analysis of the complete S segment sequences recovered for two wild
      type PUUV strains confirmed the existence of a distinct genetic lineage and also
      indicated a possible quasispecies type of Slovenian PUUV.

PMID- 16997413
TI  - Gait training after stroke: a critical reprisal.

PMID- 16997414
TI  - Bilateral isolated acute cataracts in three newly diagnosed insulin dependent
      diabetes mellitus young patients.

PMID- 16997415
TI  - Altering nucleosomes during DNA double-strand break repair in yeast.
AB  - Although chromatin remodeling has a key role in the regulation of gene
      expression, it is also important for other chromatin-based processes such as DNA
      repair, replication and recombination. ATP-dependent chromatin remodeling factors
      have unique roles in disrupting histone-DNA interactions and are targeted to gene
      promoters to 'loosen' chromatin for access of transcription factors. Recently,
      three chromatin remodeling factors with roles in transcriptional regulation have
      also been shown to be present at sites of DNA double-strand breaks (DSBs) in
      yeast. These factors control different aspects of DSB repair, suggesting that
      chromatin remodeling constitutes a key mechanism to preserve genome integrity.

PMID- 16997417
TI  - Pulmonary administration of therapeutic proteins using an immunoglobulin
      transport pathway.
AB  - We have applied a "physiologic" approach to the pulmonary delivery of therapeutic
      proteins, utilizing an immunoglobulin (antibody) transport pathway recently shown
      to be present predominantly in the conducting airways of the human respiratory
      tract. Therapeutic proteins are fused to the Fc-domain of an IgG1, allowing them
      to bind with high affinity to the antibody transport receptor, FcRn. Liquid
      aerosols are administered into the lung using normal breathing maneuvers and
      efficient delivery of several different Fc-fusion proteins has been achieved with
      retention of biological activity and an increase in circulating half-life. A new
      paradigm for the pulmonary delivery of therapeutic proteins and a fundamental
      advance in the construction of Fc-fusion proteins for this purpose will be
      described.

PMID- 16997416
TI  - Raising the curtains on interchromosomal interactions.
AB  - The chromosome conformation capture technique is used to monitor intra- and
      intermolecular chromosomal associations. By introducing an adaptation of this
      technique, Ling and colleagues have identified an unexpected coassociation
      between two loci on separate chromosomes in mouse nuclei, the imprinted Igf2-H19
      locus of chromosome 7 and the Wsb1-Nf1 locus of chromosome 11. Strikingly, this
      interaction is CCCTC-binding factor (CTCF)-dependent and strictly allele
      specific. These findings extend our appreciation for genome organization and its
      influence on gene expression and imprinting.

PMID- 16997418
TI  - Inhaled delivery of aerosolized cyclosporine.
AB  - Aerosolized cyclosporine was the first calcineurin inhibitor to be developed for
      inhaled administration. Its use as a topical immunosuppressant after lung
      transplantation is reviewed. Animal studies in transplant and non-transplant
      models are considered, as is nebulized delivery of the drug, including the
      results of scintigraphy and pharmacokinetic studies. Open label clinical studies
      of the drug for the treatment of chronic and acute lung transplant rejection are
      detailed. Placebo controlled trials for rejection prophylaxis are described and
      future directions for the drug are considered. Aerosol cyclosporine provides an
      excellent example of how inhaled aerosol delivery can provide therapeutic
      concentrations of drug in the lungs while minimizing the side effects associated
      with high systemic concentrations. In the case of lung transplantation, the drug
      is delivered directly to the airways, the location of the pathology resulting in
      most mortality in this population (chronic allograft rejection), maximizing the
      efficacy of this dose-dependent immunosuppressant.

PMID- 16997419
TI  - Emergency department sonographic measurement of optic nerve sheath diameter to
      detect findings of increased intracranial pressure in adult head injury patients.
AB  - STUDY OBJECTIVE: Our objective is to determine whether a bedside ultrasonographic
      measurement of optic nerve sheath diameter can accurately predict the computed
      tomographic (CT) findings of elevated intracranial pressure in adult head injury
      patients in the emergency department (ED). METHODS: We conducted a prospective,
      blinded observational study on adult ED patients with suspected intracranial
      injury with possible elevated intracranial pressure. Exclusion criteria were age
      younger than 18 years or obvious ocular trauma. Using a 7.5-MHz ultrasonographic
      probe on the closed eyelids, a single optic nerve sheath diameter was measured 3
      mm behind the globe in each eye. A mean binocular optic nerve sheath diameter
      greater than 5.00 mm was considered abnormal. Cranial CT findings of shift,
      edema, or effacement suggestive of elevated intracranial pressure were used to
      evaluate optic nerve sheath diameter accuracy. RESULTS: Fifty-nine patients were
      enrolled in the study. Average age was 38 years, and median Glasgow Coma Scale
      score was 15 (interquartile 6 to 15). Eight patients with an optic nerve sheath
      diameter of 5.00 mm or more had CT findings that correlated with elevated
      intracranial pressure. The sensitivity for the ultrasonography in detecting
      elevated intracranial pressure was 100% (95% confidence interval [CI] 68% to
      100%) and specificity was 63% (95% CI 50% to 76%). The sensitivity of
      ultrasonography for detection of any traumatic intracranial injury found by CT
      was 84% (95% CI 60% to 97%) and specificity was 73% (95% CI 59% to 86%).
      CONCLUSION: Bedside ED optic nerve sheath diameter ultrasonography has potential
      as a sensitive screening test for elevated intracranial pressure in adult head
      injury.

PMID- 16997420
TI  - Long-term global health deficits: yet another adverse outcome from motor vehicle
      crashes.

PMID- 16997421
TI  - Randomized clinical trial of etomidate versus propofol for procedural sedation in
      the emergency department.
AB  - STUDY OBJECTIVE: We compare the efficacy, adverse events, and recovery duration
      of etomidate and propofol for use in procedural sedation in the emergency
      department (ED). METHODS: This was a randomized nonblinded prospective trial of
      adult patients undergoing procedural sedation for painful procedures in the ED.
      Patients received either propofol or etomidate. Doses, vital signs, nasal end
      tidal CO2 (ETCO2), pulse oximetry, and bispectral electroencephalogram analysis
      scores were recorded. Subclinical respiratory depression was defined as a change
      in ETCO2 greater than 10 mm Hg, an oxygen saturation of less than 92% at any
      time, or an absent ETCO2 waveform at any time. Clinical events related to
      respiratory depression, including an increase in supplemental oxygen, the use of
      a bag-valve-mask apparatus, airway repositioning, or stimulation to induce
      breathing, were noted during the procedure. After the procedure, patients
      completed visual analog scales about perceived pain during the procedure and
      recall of the procedure. RESULTS: Two hundred twenty patients were enrolled; 214
      underwent sedation and were analyzed. One hundred five patients received
      etomidate and 109 received propofol. No clinically significant complications were
      noted. Subclinical respiratory depression was observed in 36 of 105 (34.3%)
      patients in the etomidate group and 46 of 109 (42.2%) in the propofol group
      (difference -7.9%; 95% confidence interval [CI] -20.9% to 5.1%). Myoclonus was
      noted in 21 of 105 (20.0%) patients in the etomidate group and 2 of 109 (1.8%) in
      the propofol group (difference 18.2%; 95% CI 10.1% to 26.2%). The mean difference
      between baseline systolic blood pressure and the nadir was 3.8% (95% CI 2.3% to
      5.3%) for etomidate and 7.9% (95% CI 6.1% to 9.7%) for propofol. Clinical events
      related to respiratory depression included an increase in supplemental oxygen in
      6.7% of etomidate patients and 5.5% of propofol patients (difference 1.2%; 95% CI
      -5.2% to 7.6%), the use of bag-valve-mask apparatus in 3.8% of patients in the
      etomidate groups and 4.6% in the propofol group (difference -0.8%; 95% CI -6.1%
      to 4.6%), airway repositioning in 13.3% of etomidate patients and 11.0% of
      propofol patients (effect size 2.3%; 95% CI -6.4% to 11.1%), and stimulation to
      induce breathing in 11.4% of etomidate patients and 11.9% of propofol patients
      (difference -0.5%; 95% CI -9.1% to 8.1%). The procedures were successful in 93 of
      105 (88.6%) for etomidate and 106 of 109 (97.2%) for propofol (difference -7.4%;
      95% CI -14.3% to -1.1%). CONCLUSION: Etomidate and propofol appear equally safe
      for ED procedural sedation; however, etomidate had a lower rate of procedural
      success and induced myoclonus in 20% of patients.

PMID- 16997422
TI  - Computer-assisted categorizing of head computed tomography reports for clinical
      decision rule research.
AB  - STUDY OBJECTIVE: To develop software that categorizes electronic head computed
      tomography (CT) reports into groups useful for clinical decision rule research.
      METHODS: Data were obtained from the Second National Emergency X-Radiography
      Utilization Study, a cohort of head injury patients having received head CT. CT
      reports were reviewed manually for presence or absence of clinically important
      subdural or epidural hematoma, defined as greater than 1.0 cm in width or causing
      mass effect. Manual categorization was done by 2 independent researchers blinded
      to each other's results. A third researcher adjudicated discrepancies. A random
      sample of 300 reports with radiologic abnormalities was selected for software
      development. After excluding reports categorized manually or by software as
      indeterminate (neither positive nor negative), we calculated sensitivity and
      specificity by using manual categorization as the standard. System efficiency was
      defined as the percentage of reports categorized as positive or negative,
      regardless of accuracy. Software was refined until analysis of the training data
      yielded sensitivity and specificity approximating 95% and efficiency exceeding
      75%. To test the system, we calculated sensitivity, specificity, and efficiency,
      using the remaining 1,911 reports. RESULTS: Of the 1,911 reports, 160 had
      clinically important subdural or epidural hematoma. The software exhibited good
      agreement with manual categorization of all reports, including indeterminate ones
      (weighted kappa 0.62; 95% confidence interval [CI] 0.58 to 0.65). Sensitivity,
      specificity, and efficiency of the computerized system for identifying manual
      positives and negatives were 96% (95% CI 91% to 98%), 98% (95% CI 98% to 99%),
      and 79% (95% CI 77% to 80%), respectively. CONCLUSION: Categorizing head CT
      reports by computer for clinical decision rule research is feasible.

PMID- 16997423
TI  - Improving survival from out-of-hospital cardiac arrest: back to the basics.

PMID- 16997424
TI  - Missed and delayed diagnoses in the emergency department: a study of closed
      malpractice claims from 4 liability insurers.
AB  - STUDY OBJECTIVES: Diagnostic errors in the emergency department (ED) are an
      important patient safety concern, but little is known about their cause. We
      identify types and causes of missed or delayed diagnoses in the ED. METHODS: This
      is a review of 122 closed malpractice claims from 4 liability insurers in which
      patients had alleged a missed or delayed diagnosis in the ED. Trained physician
      reviewers examined the litigation files and the associated medical records to
      determine whether an adverse outcome because of a missed diagnosis had occurred,
      what breakdowns were involved in the missed diagnosis, and what factors
      contributed to it. Main outcome measures were missed diagnoses, process
      breakdowns, and contributing factors. RESULTS: A total of 79 claims (65%)
      involved missed ED diagnoses that harmed patients. Forty-eight percent of these
      missed diagnoses were associated with serious harm, and 39% resulted in death.
      The leading breakdowns in the diagnostic process were failure to order an
      appropriate diagnostic test (58% of errors), failure to perform an adequate
      medical history or physical examination (42%), incorrect interpretation of a
      diagnostic test (37%), and failure to order an appropriate consultation (33%).
      The leading contributing factors to the missed diagnoses were cognitive factors
      (96%), patient-related factors (34%), lack of appropriate supervision (30%),
      inadequate handoffs (24%), and excessive workload (23%). The median numbers of
      process breakdowns and contributing factors per missed diagnosis were 2 and 3,
      respectively. CONCLUSION: Missed diagnoses in the ED have a complex cause. They
      are typically the result of multiple breakdowns in the diagnostic process and
      several contributing factors.

PMID- 16997425
TI  - A population-based cohort study of longer-term changes in health of car drivers
      involved in serious crashes.
AB  - STUDY OBJECTIVE: Evidence about the burden of disability after motor vehicle
      crashes has relied primarily on trauma center-based studies. We examine the
      impact of serious crashes on the longer-term health of car drivers, independent
      of natural variation, in a population-based study in Auckland, New Zealand.
      METHODS: The study population comprised 218 car drivers surviving nonfatal
      crashes in Auckland, in which at least 1 occupant in the vehicle was admitted to
      a hospital, and a representative sample of 254 car drivers in the region,
      recruited from roadside surveys. All participants were interviewed at recruitment
      (subjects reported their precrash health) and 5 and 18 months later. The drivers'
      changes in health were obtained with a global health transition indicator and the
      Short Form-36, with analyses adjusting for potential confounders. RESULTS:
      Compared with 7% of drivers in the comparison group, 43% of crash drivers
      admitted to the hospital (adjusted odds ratio 10.4; 95% confidence interval 5.5
      to 19.6) and 20% of those not admitted (odds ratio 3.3; 95% confidence interval
      1.4 to 8.3) reported that their overall health at 18-month follow-up was worse
      than at baseline (precrash). Among the drivers reporting worsened health,
      prospectively ascertained Short Form-36 scores revealed greater reductions in
      physical health in those admitted after the crash, but these scores improved from
      5 to 18 months. In contrast, mental and general health scores worsened from 5 to
      18 months in admitted and nonadmitted crash drivers. CONCLUSION: A substantial
      proportion of drivers surviving serious crashes experience reductions in longer
      term health, a burden likely to be underappreciated among those not admitted to a
      hospital. Emergency departments could serve as useful settings in which to
      develop and validate clinical decision rules that can help target services for
      crash survivors at increased risk of adverse outcomes.

PMID- 16997426
TI  - Feasibility of using near-infrared spectroscopy to diagnose testicular torsion:
      an experimental study in sheep.
AB  - STUDY OBJECTIVE: To assess whether near-infrared spectroscopy can detect
      testicular hypoxia in a sheep model of testicular torsion within 6 hours of
      experimental torsion. METHODS: This was a randomized, controlled, nonblinded
      study. Trans-scrotal, near-infrared, spectroscopy-derived testicular tissue
      saturation of oxygen values were obtained from the posterior hemiscrota of 6
      anesthetized sheep at baseline and every 15 minutes for 6 hours after either
      experimental-side, 720-degree, unilateral, medial testicular torsion and
      orchidopexy or control-side sham procedure with orchidopexy and then for 75
      minutes after reduction of torsion and pexy. Color Doppler ultrasonography was
      performed every 30 minutes to confirm loss of vascular flow on the experimental
      side, return of flow after torsion reduction, and preserved flow on the control
      side. RESULTS: Near infrared spectroscopy detected a prompt, sustained reduction
      in testicular tissue saturation of oxygen after experimental torsion. Further, it
      documented a rapid return of these values to pretorsion levels after reduction of
      torsion. Experimental-side testicular tissue saturation of oxygen fell from a
      median value of 59% (interquartile range [IQR] 57% to 69%) at baseline to 14%
      (IQR 11% to 29%) at 2.5 hours of torsion, and postreduction values were
      approximately 70%. Control-side testicular tissue saturation of oxygen values
      increased from a median value of 67% (IQR 59% to 68%) at baseline to 77% (IQR 77%
      to 94%) at 2.5 hours and remained at approximately 80% for the entire protocol.
      The difference in median testicular tissue saturation of oxygen between
      experimental and control sides, using the Friedman test, was found to be
      significant (P=.017). CONCLUSION: This study demonstrates the feasibility, in a
      sheep model, of using near-infrared spectroscopy for the noninvasive diagnosis of
      testicular torsion and for quantification of reperfusion after torsion reduction.
      The applicability of these findings, from an animal model using complete torsion,
      to the clinical setting remains to be established.

PMID- 16997427
TI  - Pentosan polysulfate protects brain endothelial cells against bacterial
      lipopolysaccharide-induced damages.
AB  - Peripheral inflammation can aggravate local brain inflammation and neuronal
      death. The blood-brain barrier (BBB) is a key player in the event. On a relevant
      in vitro model of primary rat brain endothelial cells co-cultured with primary
      rat astroglia cells lipopolysaccharide (LPS)-induced changes in several BBB
      functions have been investigated. LPS-treatment resulted in a dose- and time
      dependent decrease in the integrity of endothelial monolayers: transendothelial
      electrical resistance dropped, while flux of permeability markers fluorescein and
      albumin significantly increased. Immunostaining for junctional proteins ZO-1,
      claudin-5 and beta-catenin was significantly weaker in LPS-treated endothelial
      cells than in control monolayers. LPS also reduced the intensity and changed the
      pattern of ZO-1 immunostaining in freshly isolated rat brain microvessels. The
      activity of P-glycoprotein, an important efflux pump at the BBB, was also
      inhibited by LPS. At the same time production of reactive oxygen species and
      nitric oxide was increased in brain endothelial cells treated with LPS. Pentosan
      polysulfate, a polyanionic polysaccharide could reduce the deleterious effects of
      LPS on BBB permeability, and P-glycoprotein activity. LPS-stimulated increase in
      the production of reactive oxygen species and nitric oxide was also decreased by
      pentosan treatment. The protective effect of pentosan for brain endothelium can
      be of therapeutical significance in bacterial infections affecting the BBB.

PMID- 16997428
TI  - Increased fMRI responses during encoding in mild cognitive impairment.
AB  - Structural and functional magnetic resonance imaging (fMRI) was performed on 21
      healthy elderly controls, 14 subjects with mild cognitive impairment (MCI) and 15
      patients with mild Alzheimer's disease (AD) to investigate changes in fMRI
      activation in relation to underlying structural atrophy. The fMRI paradigm
      consisted of associative encoding of novel picture-word pairs. Structural
      analysis of the brain was performed using voxel-based morphometry (VBM) and
      hippocampal volumetry. Compared to controls, the MCI subjects exhibited increased
      fMRI responses in the posterior hippocampal, parahippocampal and fusiform
      regions, while VBM revealed more atrophy in MCI in the anterior parts of the left
      hippocampus. Furthermore, the hippocampal volume and parahippocampal activation
      were negatively correlated in MCI, but not in controls or in AD. We suggest that
      the increased fMRI activation in MCI in the posterior medial temporal and closely
      connected fusiform regions is compensatory due to the incipient atrophy in the
      anterior medial temporal lobe.

PMID- 16997429
TI  - Synthesis, characterization and in vitro antibacterial activity of new steroidal
      thiazolo quinoxalines.
AB  - Herein, we report the synthesis of different steroidal thiazolo quinoxaline
      derivatives as antibacterial agents against Escherichia coli. Steroidal ketone
      thiosemicarbazones (4-6) were obtained from corresponding ketones (1-3) by
      refluxing with thiosemicarbazide. The thiosemicarbazones on reaction with 2,3
      dichloroquinoxalines at 80 degrees C gives 3beta-acetoxy-5alpha-cholestan-6
      [thiazolo(4,5-b)quinoxaline-2-yl-hydrazone] (7), 3beta-chloro-cholestan-6
      [thiazolo(4,5-b)quinoxaline-2-yl-hydrazone] (8), and 5alpha-cholestan-6
      [thiazolo(4,5-b)quinoxaline-2-yl-hydrazone] (9). The structures of the compounds
      were evident by elemental, IR, (1)H NMR and FAB mass spectral analyses. The
      antibacterial activities of these compounds were evaluated by disk diffusion
      method against the culture of E. coli and the results were compared with the
      standard drug amoxicillin. The results reveal that the compounds are better
      antibacterial agents as compared to amoxicillin. Among all the three compounds (7
      9), compound 8 showed better zone of inhibition.

PMID- 16997430
TI  - [Treatment in primary Streptococcus pneumoniae peritonitis in adult: a case
      report and review of the literature].
AB  - INTRODUCTION: Streptococcus pneumoniae primary peritonitis is rare. The diagnosis
      is uneasy and the treatment is not standardised. CASE REPORT: We report a single
      case of S. pneumoniae primary peritonitis needing surgical treatment. DISCUSSION:
      S. pneumoniae primary peritonitis can be medically treated. Surgery is needed in
      case of sepsis, associated digestive injuries or failure of medical treatment.

PMID- 16997431
TI  - [Medullar cancer of the thyroid associated with dermal mucinosis].
AB  - INTRODUCTION: Dermal mucinosis can be associated with numerous pathologies, in
      particular involving the thyroid, but has never been described in the case of a
      medullar cancer of the thyroid (MCT). CASE-REPORT: A 69-year-old man consulted
      for a facial erythrosis, which had been developing for a few weeks without any
      identified triggering factor. The skin biopsy showed dermal mucinosis and tests
      revealed a sporadic medullar cancer of the thyroid with secondary bone, ganglion
      and medullar localizations. DISCUSSION: The association between medullar cancer
      of the thyroid and dermal mucinosis has never been described. Several hypotheses
      may explain this: the thyroid pathology itself, whatever its nature, the capacity
      of the MCT to synthesize mucin and the medullar metastatic overgrowth.

PMID- 16997432
TI  - [Acute adrenal insufficiency during unilateral adrenal hemorrhage secondary to
      the antiphospholipid syndrome].
AB  - INTRODUCTION: Acute adrenal insufficiency during antiphospholipid syndrome is
      usually due to a bilateral adrenal hemorrhage. For a patient, an unilateral
      involvement has induced an acute adrenal insufficiency. CASE REPORT: A patient
      with an antiphospholipid syndrome has developed an acute adrenal insufficiency
      with an unilateral adrenal hemorrhage. This complication was caused by a
      concurrent steroid therapy, for an associated lupus, which resulted in a
      suppression of the contralateral adrenal gland. CONCLUSION: In patients with
      antiphospholipid syndrome and concurrent steroid therapy, usually for lupus,
      unilateral adrenal hemorrhage can cause acute adrenal insufficiency. Withdrawal
      of steroid might be difficult in case of undetected bilateral hemorrhage.

PMID- 16997433
TI  - [Dermatosis-arthritis syndrome associated with Crohn's disease in a teenager].
AB  - INTRODUCTION: Pustulosis, erythema nodosum, arthritis and systemic manifestations
      are associated in the dermatosis-arthritis syndrome. It is a well recognized
      complication of the bowel ileo-jejunal bypass but it is also associated with
      inflammatory bowel diseases. EXEGESE: We report the case of an adolescent who
      presented with a dermatosis-arthritis syndrome associated to a Crohn's disease
      during a referring for pustulosis, erythema nodosum and fever. The evolution is
      complicated by proctorragia. Colonoscopy and intestinal biopsy found a Crohn's
      disease. Cutaneous and intestinal symptoms quickly improved with systemic
      corticosteroids. CONCLUSION: The dermatosis-arthritis syndrome can be associated
      with bowel bypass and with inflammatory bowel disease, more frequently with
      ulcerative colitis than with Crohn's disease. It consists in a vesiculo-pustular
      eruption, erythema nodosum, fever, arthritis and ocular manifestations.
      Histopathology bears a strong resemblance with Sweet's syndrome. Physiopathology
      implicates microbial proliferation, formation of immune complex against skin and
      activation and migration of neutrophils and increasing factors. The treatment is
      based on corticosteroids and non steroid anti-inflammatory drugs or dapsone.

PMID- 16997434
TI  - Effectiveness of influenza vaccination: a survey within the Italian Ministry of
      Health personnel.
AB  - An initiative of active prevention, to promote an influenza vaccination
      programme, has been carried out in the Ministry of Health of Rome, Directorate
      General of Health Prevention: during October 2004 influenza vaccine has been
      actively offered to all the employees; 46 out of the 129 workers (about 36% of
      the total) accepted to be vaccinated. Afterward, the propensity to get influenza
      of the vaccinated has been compared with that of a control group, operating in
      the same setting, but not vaccinated. Taking into account that the groups in
      question is far too small, the statistical results showed that influenza
      vaccination of healthy working adults did not reduce the rates of influenza-like
      illness (ILI), in addition, the difference between average duration of disease in
      unvaccinated persons was not statistically significant.

PMID- 16997435
TI  - Determination of dose rates from natural radionuclides in dental materials.
AB  - Different types of materials used for dental prosthetics restoration, including
      feldspathic ceramics, glass ceramics, zirconia-based ceramics, alumina-based
      ceramics, and resin-based materials, were investigated with regard to content of
      natural radionuclides by means of thermoluminescence beta dosimetry and gamma
      spectrometry. The gross beta dose rate from feldspathic and glass ceramics was
      about ten times higher than the background measurement, whereas resin-based
      materials generated negligible beta dose rate, similarly to natural tooth
      samples. The specific activity of uranium and thorium was significantly below the
      levels found in the period when addition of uranium to dental porcelain materials
      was still permitted. The high-beta dose levels observed in feldspathic porcelains
      and glass ceramics are thus mainly ascribable to (40)K, naturally present in
      these specimens. Although the measured values are below the recommended limits,
      results indicate that patients with prostheses are subject to higher dose levels
      than other members of the population. Alumina- and zirconia-based ceramics might
      be a promising alternative, as they have generally lower beta dose rates than the
      conventional porcelain materials. However, the dosimetry results, which imply the
      presence of inhomogeneously distributed clusters of radionuclides in the sample
      matrix, and the still unsuitable structural properties call for further
      optimization of these materials.

PMID- 16997436
TI  - Estrogenic activity associated with organochlorine compounds in fish extracts
      from European mountain lakes.
AB  - Fish muscle extracts from ten European mountain lakes were analyzed for
      organochlorine compounds (OCs) and estrogenic activity, the latter by a
      recombinant yeast assay based on the human estrogen receptor. Seventy percent of
      the samples showed estrogenic activity above detection limits and a subset of
      five samples showed estrogenic activities, equivalent to more than 10,000 pg/g of
      estradiol. These highly estrogenic samples occurred in two lakes, Velke Hincovo
      in the Tatra Mountains and Redon in the Pyrenees. Principal component analysis
      correlated estrogenic activity of muscle extracts to fish age and concentrations
      of the more chlorinated polychlorobiphenyls (PCBs). This is consistent with
      previously observed correlations of these PCBs with fish age. In addition, most
      fish with high estrogenic activity were found in lakes containing high OC levels
      in the sediments, which gives further ground to atmospheric deposition of
      anthropogenic pollutants as main process leading to the observed endocrine
      disruption effects.

PMID- 16997437
TI  - A functional analysis of danger and safety signals in anxiety disorders.
AB  - Research in experimental psychopathology indicates that predictability and
      controllability of threatening events mediate the development, maintenance, and
      modification of anxiety disorders. We propose that a more thorough analysis of
      predictability and controllability requires the explication of danger and safety,
      and those events that provide such signal functions. Although most research is
      concerned with the identification of signals that predict danger, relatively
      little attention has been given to the identification of signals that predict
      safety. The current manuscript outlines the functional analysis of both danger
      and safety signals as they relate to the various disorders of anxiety.
      Consideration of pharmacological treatments suggests that the modification of
      danger and safety signals may function only as incidental features of the
      intervention. The potential advantages of cognitive-behavioral interventions that
      maximize treatment-specific self-control of signal functions are discussed.

PMID- 16997438
TI  - Birth outcomes among urban African-American women: a multilevel analysis of the
      role of racial residential segregation.
AB  - Residential segregation is a common aspect of the urban experiences of African
      Americans in the United States (US), yet few studies have considered how
      segregation might influence perinatal health. Here, we develop a conceptual model
      of relationships between segregation and birth outcomes and test the implications
      of the model in a sample of 434,376 singleton births to African-American women
      living in 225 US Metropolitan Statistical Areas (MSAs). Data from the National
      Center for Health Statistics 2002 birth files were linked to data from the 2000
      US Census and two distinct measures of segregation: an index of isolation (the
      probability that an African-American resident will encounter another African
      American resident in any random neighborhood encounter) and an index of
      clustering (the extent to which African-Americans live in contiguous
      neighborhoods). Using multilevel regression models, controlling for individual-
      and MSA-level socioeconomic status and other covariates, we found higher
      isolation was associated with lower birthweight, higher rates of prematurity and
      higher rates of fetal growth restriction. In contrast, higher clustering was
      associated with more optimal outcomes. We propose that isolation reflects factors
      associated with segregation that are deleterious to health including poor
      neighborhood quality, persistent discrimination and the intra-group diffusion of
      harmful health behaviors. Associations with clustering may reflect factors
      associated with segregation that are health-promoting such as African-American
      political power empowerment, social support and cohesion. Declines in isolation
      could represent positive steps toward improving birth outcomes among African
      American infants while aspects of racial contiguity appear to be mitigating or
      indeed beneficial. Segregation is a complex multidimensional construct with both
      deleterious and protective influences on birth outcomes, depending on the
      dimensions under consideration. Further research to understand racial/ethnic and
      economic health disparities could benefit from a focus on the contributory role
      of neighborhood attributes associated with the dimensions segregation and other
      social geographies.

PMID- 16997439
TI  - Facility and county effects on racial differences in nursing home quality
      indicators.
AB  - This study's goal was to examine the effects of nursing home (NH) and county
      racial mix on quality of care in NHs. We examined quality indicator (QI) outcomes
      for residents in 408 urban New York NHs in July through September, 1995. The QI
      outcomes studied were restraint and antipsychotic drug use (for low and high-risk
      residents), and at study commencement, these QIs were being used by the Centers
      for Medicare and Medicaid Services to monitor the quality of care in USA Medicare
      and/or Medicaid-certified NHs. A hierarchical modeling approach was used to
      properly reflect the nesting of both residents within NHs and NHs within
      counties. Separate regression models were fit to the two strata of interest
      (Urban Non-Hispanic Whites and Urban African Americans) to test, for each race
      group, the effect on quality of residing in NHs and counties with higher
      proportions of African Americans (than state medians). Descriptive analyses found
      that, compared to Whites, the unadjusted restraint rate was lower for African
      Americans while the antipsychotic drug rate was higher. For both race groups,
      multi-level analyses showed residence in for-profit NHs was associated with
      higher likelihoods of being restrained, and of receiving antipsychotic drugs.
      Also, for both race groups, residence in NHs with higher proportions of African
      Americans was associated with lower likelihoods of being restrained and with
      higher, statistically nonsignificant, likelihoods of receiving antipsychotic
      drugs. Higher NH nurse staffing ratios were associated with higher likelihoods of
      being restrained and with lower likelihoods of antipsychotic drug use
      (statistically significant for low-risk African-Americans). Findings support the
      notion that differential care is provided in USA NHs caring for higher
      proportions of African-American residents and thereby suggest intervention at the
      organizational level is warranted to improve QI outcomes for both race groups.

PMID- 16997440
TI  - The interpersonal experience of health care through the eyes of patients with
      diabetes.
AB  - Patients with chronic illness often face challenges navigating the US health care
      system because of the system's lack of coordination and continuity. Patients with
      more difficulty relying on others and with reluctance in engaging frequently or
      in-depth with providers, face even greater challenges obtaining optimal health
      care in this system. Using a self-report measure of attachment style, we selected
      patients with varying degrees of comfort and trust in relationships. We conducted
      qualitative semi-structured interviews with a purposive sample of 27 patients
      with type 2 diabetes attending the University of Washington Diabetes Care Center
      in Seattle to explore issues of trust and collaboration in the health care
      setting. We used a constant comparative approach in which contemporaneous data
      collection and analysis took place. A subset of patients with fearful and
      dismissing attachment style reported having low levels of trust and an inability
      to collaborate with others of longstanding duration. Many aspects of the current
      health care system, such as its rushed, impersonal nature and a perceived "wall"
      between providers and patients were frustrating for most study patients. Patients
      with fearful and dismissing attachment style reported that these aspects of the
      health care system often interfered with their ability to partner with providers
      but also reported that patient-centered attitudes and behaviors by providers
      could improve their trust and ability to engage in the health care system.
      Implications of using a conceptual model of attachment theory to improve patient
      centered care and customer service are discussed.

PMID- 16997441
TI  - The shackles of misfortune: social adversity assessment and representation in a
      chronic-disease epidemiological setting.
AB  - Research evidence is accumulating to support an association between social
      adversity and the development of predisease processes and physical disease
      outcomes. While methodological advances have been achieved in the assessment of
      social adversity, significant barriers remain to their adoption in chronic
      disease epidemiological settings consequent upon the need to limit participant
      burden and restrictions imposed by cohort size and cost. A large-scale population
      based cohort study, as part of the European Prospective Investigation into
      Cancer, Norfolk, UK, provided an opportunity to include a comprehensive postal
      assessment of social adversity. A total of 20,921 participants reported details
      of 16,031 adverse circumstances during childhood, 119,056 life events and 106,170
      person-years of difficulties experienced during adulthood. Impact and adaptation
      indices were constructed from responses to questions regarding specific life
      events experienced. There was no evidence that younger participants reported more
      difficulties in childhood than those who were older, and no evidence of
      clustering of loss events involving the death of first degree relatives according
      to their recency. However, there was evidence of recall bias for events not
      involving loss with increased event rates observed in the few years immediately
      prior to questionnaire completion. Women reported similar events as more
      upsetting, and that they took longer to get over their effects, than men.
      Difficulties experienced in childhood, life events and difficulties in adulthood,
      event impact and adaptation were all associated with worse physical functional
      health. Reported slow adaptation to the effects of life events was associated
      with the largest decrement in physical functional health. These findings
      strengthen the rationale for including a collection of comprehensive social
      adversity data within chronic disease epidemiological settings and offer promise
      for aiding understanding of individual differences in physical disease aetiology.

PMID- 16997442
TI  - [Congenital haemangiomas and other rare infantile vascular tumours].
AB  - A number of infantile tumours, far less frequent than infantile haemangiomas,
      were long assimilated to them. Today they are clearly individualised, based on
      distinctive clinical and pathologic features, and this difference has been
      supported by the discovery of new immunophenotypic markers such as GLUT1. GLUT1
      stains 100% of infantile haemangiomas and none of the other infantile vascular
      tumours. Congenital haemangiomas represent a group of vascular tumours still
      under evaluation as they have slightly heterogeneous presentation. Their
      prognosis is better appraised and their therapeutic management has improved. They
      are all fully grown in utero and they do not experience postnatal proliferation
      like haemangiomas do. Some of them (RICH--Rapidly Involuting Congenital
      Haemangioma) undergo spontaneous involution during the first year. Others (NICH-
      Non Involuting Congenital Haemangioma) persist lifelong. Tufted angioma and
      kaposiform haemangioendothelioma are histopathologically well characterized; in
      addition they are now considered as part of a same spectrum of vascular tumours,
      with the contribution of lymphatic endothelial cells in their proliferation. Both
      are clearly the tumours able to create platelet trapping, thrombocytopenia and
      the life-threatening Kasabach-Merritt syndrome. However they may occur as
      isolated tumours, without thrombocytopenia but with cosmetic, and sometimes
      function-impairing, consequences.

PMID- 16997443
TI  - [Hemangioma: complications].
AB  - Hemangioma (HMG) is a benign tumour of the child generally evolving to
      spontaneous regression. Sometimes this evolution can become complicated in a more
      or less serious way according to its localization or of its importance. If local
      complications are, in the most of cases, without gravity, complications of a
      general nature like thrombopenia or cardiac failure may compromise the vital
      prognosis. There are in addition serious forms where, according to its
      localization or its importance, the HMG can compromise the aesthetic, or
      functional even vital outcome.

PMID- 16997444
TI  - [Vascular anomalies. Introduction].

PMID- 16997445
TI  - [Early surgical treatment of cutaneous hemangiomas].
AB  - Infantile hemangioma appears after the birth as a vascular tumor, which is known
      for its characteristic evolution in 3 phases: rapid augmentation then
      stabilization and involution on several years with in the best cases, classical
      "restitutio ad integrum". Usual surgical attitude is abstention and surgery is
      proposed only in order to treat sequel. But some particular situations require
      early surgery for life-threatening lesions or in case of functional impairment.
      Surgery consists in these cases in a simple volumetric diminution of the tumor
      with no aim for esthetic improvement. Other kinds of hemangiomas require an early
      surgical treatment before their complete involution. In some particular
      locations, deformation or growth delay can occur due to the lesion's development.
      In some cases, hemangiomas present a delayed involution with minor regression
      capacity; these are mainly located on the median part of the face and have
      principally a subcutaneous development. Early surgery can be proposed in order to
      avoid definitive deformation or growth impairment of adjacent structures. It
      should be performed before school age and before occurrence of psychological
      difficulties. Surgery is indicated in a perspective of esthetic improvement.
      Surgical procedure consists first in modeling excision followed by simple repair
      technique as linear suture or purse string closure; complex surgical procedures
      inducing their own sequels are usually inappropriate.

PMID- 16997446
TI  - [Medical treatment of juvenile hemangiomas].
AB  - Infantile hemangioma always involute in 5 to 7 years. However, 10% of
      proliferating hemangiomas will necessitate a therapeutic approach, often medical,
      in order to avoid life or organ threatening, fonctional or esthetic sequelae.
      "Which hemangioma need to be treated, when and how" are important questions for
      the optimal management of infantile hemangiomas. Corticotherapy is still the
      treatment of choice for these lesions. Other anti-angiogenic molecules have also
      been successfully used such as interferon alfa-2a and vincristine. This chapter
      tries to answer these questions and detail the different medical modalities for
      the treatment of infantile hemangioma.

PMID- 16997447
TI  - [Cutaneous hemangioma: clinical aspects].
AB  - Infantile cutaneous hemangioma is a benign vascular tumour present at 10% of the
      infants. It forms part of the group of the vascular tumours in the classification
      of International Society for Vascular Anomalies (ISSVA). Clinical diagnosis is
      easy in its triphasic typical form with a phase of sometimes brutal postnatal
      growth, a phase of stabilization and a phase of slow secondary regression.
      Classically, it is presented in the form of a mass or stains cutaneous red, of a
      subcutaneous mass or, generally, of a mixed form associating the two aspects.

PMID- 16997448
TI  - [Pathogenesis and genetics of vascular anomalies].
AB  - Vascular anomalies, divided into vascular tumors and vascular malformations, are
      localized defects of angiogenesis. Hemangiomas appear soon after birth, grow
      quickly, and then spontaneously, but slowly, disappear. In contrast, vascular
      malformations are congenital defects of vascular development that grow
      proportionately with the child. Most vascular anomalies are considered non
      hereditary. However, due to detailed analysis inherited forms have been observed,
      which has led to identify mutations in three genes causing familial vascular
      malformations: in the angiopoietin receptor TIE2 in mucocutaneous venous
      malformations (VMCM), in glomulin in glomuvenous malformations (GVM) and in RASA1
      in the newly recognized phenotype capillary malformation-arteriovenous
      malformation (CM-AVM). Identification of the causative genes has permitted more
      precise diagnosis and differential diagnosis, evaluation of phenotypic
      variability among patients with a proven mutation, study of used treatments in
      more homogeneous patient groups, and elucidation of the etiopathogenic mechanisms
      behind vascular malformations. Further studies are needed to unravel the role of
      genetic variations in the various vascular malformations and to unravel the
      precise molecular mechanisms that lead to development of these vascular lesions.
      This should provide development of new-targeted therapies.

PMID- 16997449
TI  - Membrane transport function in primary cultures of human proximal tubular cells.
AB  - To further develop primary cultures of human proximal tubular (hPT) cells for
      study of drug disposition, we determined kinetics and protein expression of
      several key transporters for organic anions and cations, peptides, and neutral
      amino acids. p-Aminohippurate uptake exhibited similar kinetics as published
      values, was inhibited by cephaloridine, cimetidine, methotrexate, and urate,
      consistent with function of both organic anion transporter 1 (OAT1) and OAT3.
      Transport rates by organic cation transporters (OCTs) were up to three-fold
      higher than those of OATs. Of the OCT substrates tested, triethanolamine
      exhibited the highest transport rates across the basolateral membrane (BLM).
      OCTN1 exhibited high-affinity, low-capacity BLM transport of l-carnitine.
      Glycylsarcosine transport by PepT2 was rapid and comparable to that of OCTs.
      Amino acid System L on the BLM exhibited comparable kinetic parameters for
      transport of l-leucine as the OATs. Efflux of verapamil across the brush-border
      membrane by P-glycoprotein was very rapid. Expression of carriers was generally
      maintained throughout 5 days of culture. Of the four OAT proteins studied (OAT1
      4), expression of OAT1 and OAT3 was the most readily detected and exhibited
      interindividual variation. OCTN2 was the major OCT in hPT cells. Expression was
      also quantified for multidrug resistance-associated proteins 2 and 5 and P
      glycoprotein. These results show that primary cultures of hPT cells express a
      diverse array of transporters for major classes of important drugs and are
      suitable for study of drug transport and disposition and assessment of potential
      drug-drug interactions in human kidney.

PMID- 16997450
TI  - The potential for sodium hexametaphosphate (SHMP) found in common children drinks
      to limit acid production in the oral biofilm.
AB  - OBJECTIVE: Sodium hexametaphosphate (SHMP) is a widely used industrial
      preservative commonly found in children's drinks. In this paper we examined the
      effect of SHMP incorporated into children's drinks on acid production by the oral
      biofilm by monitoring salivary concentrations of lactic acid. MATERIALS AND
      METHOD: Twelve healthy adult subjects with an average age 36 years (range 26-54
      years) consumed 10 ml from four children's beverages (Coca Cola and three types
      of Sunny Delight supplemented with SHMP) and a standard solution of sucrose.
      Saliva was collected at intervals following exposure of the oral biofilm to the
      drinks and the clearance of carbohydrates and the appearance of lactate was
      measured using standard enzymatic techniques. RESULTS: All the carbohydrates
      derived from the drinks were cleared from saliva within 15 min of consumption.
      Comparison of two drinks [Sunny D Normal and Sunny C] with the same carbohydrate,
      but different SHMP concentrations suggested that SHMP in these beverages had no
      significant effect on acid production. CONCLUSIONS: In this clinical study the
      role of SHMP, incorporated in common beverages, did not inhibit acid production
      from carbohydrates.

PMID- 16997451
TI  - Purification and characterization of a 34-kDa, heat stable glycoprotein from
      Synadenium grantii latex: action on human fibrinogen and fibrin clot.
AB  - Latex glycoprotein (LGP) from Synadenium grantii latex was purified by the
      combination of heat precipitation and gel permeation chromatography. LGP is a
      heat stable protein even at 80 degrees C showed a sharp single band both in SDS
      PAGE as well as in native (acidic) PAGE. LGP is a monomeric protein appears as
      single band under reducing condition. It is a less hydrophobic protein showed
      sharp single peak in RP-HPLC with retention time of 13.3 m. The relative
      molecular mass of LGP is 34.4 kDa. CD spectrum of LGP explains less content of
      alpha-helix (7%), and high content of beta-pleated sheets (48%) and random coils
      (46%). The N-terminal sequence of LGP is D-F-P-S-D-W-Y-A-Y-E-G-Y-V-I-D-R-P-F-S.
      Purified LGP is a fibrinogen degrading protease hydrolyses all the three subunits
      in the order of Aalpha, Bbeta and gamma. The hydrolytic pattern is totally
      different from plasmin as well as thrombin. LGP reduces recalcification time from
      165 to 30 s with citrated human plasma but did not show thrombin like as well as
      factor Xa-like activity. Although LGP induces procoagulant activity, it
      hydrolyses partially cross-linked fibrin clot. It hydrolyses all the subunits of
      partially cross-linked fibrin clot (alpha- chains, beta-chain and gamma-gamma
      dimer). LGP is a serine protease, inhibited by PMSF. Other serine protease
      inhibitors, aprotinin and leupeptin did not inhibit the caseinolytic activity as
      well as fibrinogenolytic activity. We report purification and characterization of
      a glycoprotein from Synadenium grantii latex with human fibrino(geno)lytic
      activity.

PMID- 16997453
TI  - Drug administration via the laryngeal mask airway.

PMID- 16997454
TI  - Single cell studies and simulation of cell-cell interactions using oscillating
      glycolysis in yeast cells.
AB  - The observation of oscillations in the concentrations of NADH and other
      intermediates in glycolysis in dense yeast cell suspensions is generally believed
      to be the result of synchronization of such oscillations between individual
      cells. The synchrony is believed to be a property of cell density and the
      question is: does metabolism in each individual yeast cell continue to oscillate,
      but out of phase, in the absence of synchronization? Here we have used high
      sensitivity fluorescence microscopy to measure NADH in single isolated yeast
      cells under conditions where we observe oscillations of glycolysis in dense cell
      suspensions. However, we have not been able to detect intracellular oscillations
      in NADH in these isolated cells, which cannot synchronize their metabolism with
      other cells. However, addition of acetaldehyde to a single cell as pulses with a
      frequency similar to the oscillations in dense cell suspensions will induce
      oscillations in that cell. Ethanol, another product of glycolysis, which has been
      proposed as a synchronizing agent of glycolysis in cells, was not able to induce
      oscillations when added as pulses. The experiments support the notion that the
      intracellular oscillations are associated with the cell density of the yeast cell
      suspension and mediated by acetaldehyde and perhaps also other substances.

PMID- 16997455
TI  - Sperm retrieval rates in subgroups of primary azoospermic males.
AB  - OBJECTIVES: Men presenting with primary infertility and azoospermia may be
      offered surgical sperm retrieval (SSR) as a prelude to intracytoplasmic sperm
      injection (ICSI). We evaluated sperm retrieval rates in subgroups of men with
      azoospermia, based on obstructive aetiology, testicular volume and FSH. METHODS:
      106 patients with primary infertility underwent clinical evaluation and SSR with
      percuataneous epididymal aspiration (PESA) and/or testicular sperm extraction
      (TeSE) by a single urologist over a five year period. Ten percent of this group
      (11 patients) had a clear cause of obstruction, congenital absence of the vas
      deferens (CBAVD), labelled group A. Ninety percent (95 patients) had no definite
      cause of obstruction, labelled group B. RESULTS: All eleven patients in group A
      had adequate sperm retrieved, compared with 56% of 95 men in group B. Clinical
      pregnancy and live birth rates were 47% and 44% for group A respectively compared
      with 21% and 20% for group B. Twenty-one men had testes <4 cm and FSH>10; a
      significantly lower sperm retrieval rate was seen in this subgroup (29%) compared
      to men with normal testicular volume and FSH (77%), p=0.0001, which corresponded
      to a LBR of 28% and 14% respectively. CONCLUSIONS: In the absence of testicular
      histology prior to SSR clinical parameters can be used to aid in counselling.
      Azoospermic males with normal sized testes and normal FSH can expect acceptable
      numbers of sperm to be retrieved by SSR for ICSI. Less than one third of men with
      raised FSH and small testes will have successful SSR.

PMID- 16997456
TI  - Global rhythmic activities in hippocampal neural fields and neural coding.
AB  - Global oscillations of the neural field represent some of the most interesting
      expressions of the hippocampal activity, being related also to learning and
      memory. To study oscillatory activities of the CA3 field in theta range, a model
      of this sub-field of Hippocampus has been formulated. The model describes the
      firing activity of CA3 neuronal populations within the frame of a kinetic theory
      of neural systems and it has been used for computer simulations. The results show
      that the propagation of activities induced in the neural field by hippocampal
      afferents occurs only in narrow time windows confined by inhibitory barrages,
      whose time-course follows the theta rhythm. Moreover, during each period of a
      theta wave, the entire CA3 field bears a firing activity with peculiar space-time
      patterns, a sort of specific imprint, which can induce effects with similar
      patterns on brain regions driven by the hippocampal formation. The simulation has
      also demonstrated the ability of medial septum to influence the global activity
      of the CA3 pyramidal population through the control of the population of
      inhibitory interneurons. At last, the possible involvement of global population
      oscillations in neural coding has been discussed.

PMID- 16997457
TI  - Hypoxia influences vasculogenic mimicry channel formation and tumor invasion
      related protein expression in melanoma.
AB  - BACKGROUND: Hypoxia can enhance tumor cell invasion and metastasis. The cause and
      the molecular mechanism are still not clear. METHODS: In our study, mouse
      melanoma B16 cells were inoculated into mouse ischemic limbs and non-ischemic
      controls and the engrafted melanomas were subsequently observed. Vasculogenic
      mimicry channels in melanoma tumors of the two groups were counted and the
      expression of HIF-1alpha, MMP-2, MMP-9 and VEGF was assessed by
      immunohistochemical staining. Formalin-fixed, paraffin-embedded tissues were used
      for immunohistochemical staining. RESULTS: In the early stage of engrafted
      melanoma growth, the size of melanomas in ischemic limbs increased slower than in
      the controls. However, later there was no obvious difference in their size.
      Melanoma tumors in the ischemic group had more vasculogenic mimicry channels than
      those in the controls (P=0.039). Similarly, the expression of HIF-1alpha, MMP-2,
      MMP-9 and VEGF was higher in the ischemic group than in the non-ischemic controls
      (P=0.024, 0.047, 0.007 and 0.025, respectively). There was a positive association
      in melanoma cells of the ischemic group between expression of HIF-1alpha and
      VEGF, and also between MMP-9 and MMP-2. In the ischemic group, there was
      statistical significance for the correlation between HIF-1alpha and VEGF
      expression (r=0.456, P=0.038). Furthermore, MMP-2 expression was positively
      correlated with MMP-9 and VEGF expression (r=0.589 and 0.502, P=0.008 and 0.024,
      respectively). CONCLUSIONS: Melanoma cells in a hypoxic microenvironment
      increased HIF-1alpha expression and induced the formation of vasculogenic mimicry
      channels to acquire an adequate blood supply. On the other hand, the expression
      of MMP-2 and MMP-9 in tumor tissue increased to enhance the invasiveness. HIF
      1alpha, MMP-2 and MMP-9 may be associated with the failure of stop-flow perfusion
      in some patients with melanoma.

PMID- 16997458
TI  - Mutant p53 facilitates pro-angiogenic, hyperproliferative phenotype in response
      to chronic relative hypoxia.
AB  - There is much controversy in the literature regarding the role of p53 status
      response on hypoxia inducible factor (HIF) signaling in response to chronic
      relative hypoxia (CRH). The goal of this paper was to methodically examine this
      response in isogenically matched tumor cells. We report that p53-mutant (MUT)
      cells, versus p53-wild-type (WT) cells, showed decreased apoptosis, increased
      cell proliferation with higher basal HIF-1alpha levels in response to CRH. In
      addition, we found increased HIF-mediated transactivation and increased VEGF
      release with decreased HIF-1alpha/p53 and HIF-1alpha/MDM-2 partnering in p53-MUT
      versus p53-WT cells in response to CRH.

PMID- 16997459
TI  - Ischemia-reperfusion alters the immunolocalization of glial aquaporins in rat
      retina.
AB  - Glial cells control the retinal osmohomeostasis, in part via mediation of water
      fluxes through aquaporin (AQP) water channels. By using immunohistochemical
      staining, we investigated whether ischemia-reperfusion of the rat retina causes
      alterations in the distribution of AQP1 and AQP4 proteins. Transient ischemia was
      induced in retinas of Long-Evans rats by elevation of the intraocular pressure
      for 60 min. In control retinas, immunoreactive AQP1 was expressed in the outer
      retina and by distinct amacrine cells, and AQP4 was expressed by glial cells
      (Muller cells and astrocytes) predominantly in the inner retina. After ischemia,
      retinal glial cells in the nerve fiber/ganglion cell layers strongly expressed
      AQP1. The perivascular staining around the superficial vessels altered from AQP4
      in control retinas to AQP1 in postischemic retinas. The data suggest that the
      glial cell-mediated water transport in the retina is altered after ischemia
      especially at the superficial vessel plexus.

PMID- 16997460
TI  - Effect of APOE polymorphisms on early responses to traumatic brain injury.
AB  - To investigate the relationship between apolipoprotein E (APOE) polymorphisms and
      the severity of traumatic brain injury (TBI) in acute stage in the cohort of
      mainland Chinese patients. We prospectively identified admissions to the two
      neurosurgical departments for head injury. A total of 110 subjects with TBI (80
      males and 30 females, with mean age of 43.87 years) were enrolled from December
      2003 to May 2004, and demographic and clinical data were collected. Venous blood
      was collected from patients with TBI on admission to determine the APOE genotype
      polymorphisms. The APOE genotyping was performed by means of PCR-RFLP. The
      deterioration of patients' condition in acute stage (<7 days after TBI) was
      judged by either of following criteria: decrease of GCS, increase in hematoma
      volume or delayed hematoma both detected by repeated CT scanning. Chi2-test and
      logistic regression analyses were done by SPSS. The distributions of APOE
      genotypes and alleles matched Hardy-Weinberg law. In 110 Chinese patients, 19
      subjects presented with deteriorated clinical condition after hospitalization,
      and seven of 17 patients with APOE epsilon4 (41.2%) had a deteriorated condition
      which was significantly different from those without APOE epsilon4 (12 of 93
      patients, 12.9%, P=0.01). However, neither the presence of epsilon2 nor of
      epsilon3 was significantly different from those absent of it (P>0.05). Logistic
      regression analyses showed that APOE epsilon4 was a risk factor (OR=4.836,
      P=0.011, 95% CI 1.443-16.208) to predispose to clinical deterioration after
      adjusting for patient age, sex, smoking or not, alcohol-drinking or not, injury
      severity, injury mechanisms, treatments, and pattern of TBI. This finding
      suggests that the patients with APOE epsilon4 predispose to clinical
      deterioration in acute phase after TBI and APOE polymorphisms play a role in
      early responses to TBI.

PMID- 16997461
TI  - Vestibular efferents contain peripherin.
AB  - Vestibular efferents have a common origin with the motoneurons of the facial
      nerve. In adults they share a number of common features, such as the same
      transmitter. Here we show using retrograde transport and immunohistochemistry,
      that the vestibular efferents, like facial motoneurons, contain peripherin. This
      supports the suggestion that peripherin-positive fibers at the apex of the
      cristae ampullaris are efferents.

PMID- 16997462
TI  - Propionic acid induces convulsions and protein carbonylation in rats.
AB  - Propionic acid (PA) accumulates in patients with propionic acidemia, an inherited
      metabolic disorder caused by the deficiency of propionyl-CoA carboxylase activity
      that is clinically characterized by neurological dysfunction, including seizures.
      However, it is not known whether PA causes seizures in experimental animals. In
      the current study, we investigated whether intrastriatal injection of PA (0.6-6
      micromol) causes seizures and alters protein carbonyl content in the striatum of
      adult rats. The injection of PA caused the appearance of seizures and increased
      protein carbonyl content in injected and noninjected striata. PA-induced seizures
      and increased protein carbonylation in the striatum were prevented by the
      injection of MK-801 (3 nmol/0.5 microL). Our results suggest that PA causes
      seizures and oxidative damage by NMDA receptor-mediated mechanisms. The
      involvement of NMDA receptors in the pathogenesis of propionic acidemia is
      suggested.

PMID- 16997463
TI  - Differential effects of cannabis extracts and pure plant cannabinoids on
      hippocampal neurones and glia.
AB  - We have shown previously that the plant cannabinoid cannabidiol (CBD) elevates
      intracellular calcium levels in both cultured hippocampal neurones and glia.
      Here, we investigated whether the main psychotropic constituent of cannabis,
      Delta(9)-tetrahydrocannabinol (THC) alone or in combination with other cannabis
      constituents can cause similar responses, and whether THC affects the responses
      induced by CBD. Our experiments were performed with 1 microM pure THC (pTHC),
      with 1 microM pure CBD (pCBD), with a high-THC, low CBD cannabis extract (eTHC),
      with a high-CBD, low THC cannabis extract (eCBD), with a mixture of eTHC and eCBD
      (THC:CBD=1:1) or with corresponding 'mock extracts' that contained only pTHC and
      pCBD mixed in the same proportion as in eTHC, eCBD or the 1:1 mixture of eTHC and
      eCBD. We detected significant differences in neurones both between the effects of
      pTHC and eTHC and between the effects of pCBD and eCBD. There were also
      differences between the Ca(2+) responses evoked in both neurones and glia by eTHC
      and mock eTHC, but not between eCBD and mock eCBD. A particularly striking
      observation was the much increased response size and maximal responder rates
      induced by the mixture of eTHC and eCBD than by the corresponding 1:1 mixture of
      pTHC and pCBD. Our data suggest that THC shares the ability of CBD to elevate
      Ca(2+) levels in neurones and glia, that THC and CBD interact synergistically and
      that the cannabis extracts have other constituents yet to be identified that can
      significantly modulate the ability of THC and CBD to raise Ca(2+) levels.

PMID- 16997464
TI  - Mutations in DJ-1 are rare in familial Parkinson disease.
AB  - Mutations in DJ-1 (PARK7) are one cause of early-onset autosomal-recessive
      parkinsonism. We screened for DJ-1 mutations in 93 affected individuals from the
      64 multiplex Parkinson disease (PD) families in our sample that had the highest
      family-specific multipoint LOD scores at the DJ-1 locus. In addition to
      sequencing all coding exons for alterations, we used multiplex ligation-dependent
      probe amplification (MLPA) to examine the genomic copy number of DJ-1 exons. A
      known polymorphism (R98Q) was found in five PD subjects, once as a homozygote and
      in the other four cases as heterozygotes. No additional missense mutations and no
      exon deletions or duplications were detected. Our results, in combination with
      those of previous studies, suggest that alterations in DJ-1 are not a common
      cause of familial PD.

PMID- 16997465
TI  - Identification and localization of procalcitonin-like immunoreactivity in the rat
      hypothalamus.
AB  - Procalcitonin (PCT) is a 116-amino acid polypeptide physiologically produced, as
      the precursor protein of calcitonin (CT), in the parafollicular cells of the
      thyroid gland, but physiological functions and other major sources of PCT remains
      unclear. The distribution of PCT-like immunoreactivity (PCT-LI) in the rat
      hypothalamus was examined by immunohistochemistry using a monoclonal antibody
      raised against the mid-region of human PCT (60-77-amino acid fragment). This
      antibody cross-reacts well with rat PCT and immature CT, but it cross-react
      poorly with free mature CT. Abundant expression of PCT-LI was found in zones at
      the interface between brain and cerebrospinal fluid (CSF) such as the ependymal
      layer and ventral glia limitans (VGL). Double labeling of PCT and glial
      fibrillary acidic protein (GFAP) identified this population of small cells as
      astrocytes, possibly tanycytes, a type of specialized glial cell that interacts
      in neuroendocrine functional dynamics. The fibers of these cells extend to
      circumventricular organs (CVOs) and to astrocytes located inside the parenchyma
      of key autonomic regulatory hypothalamic areas, with highest densities in the
      supraoptic nucleus (SO), arcuate nucleus (Arc), area postrema (AP), median
      eminence (ME), medial preoptic nucleus, tuber cinereum, and accessory
      neurosecretory nuclei. No strongly labeled cells were found in the
      paraventricular nucleus. The wide distribution of PCT-LI in the hypothalamus, in
      close correspondence with previous mapping of CT receptors in the rat brain,
      suggests that PCT may influence a multitude of biological activities associated
      with the hypothalamic-pituitary axis.

PMID- 16997466
TI  - Lin(-)CD34(-) bone marrow cells from adult mice can differentiate into neural
      like cells.
AB  - Numerous studies have shown that some populations of bone marrow cells (BMCs)
      have the capacity to differentiate into neural cells, which is useful for
      repairing brain lesions. In this paper, we analyze neural differentiation
      features of lineage-negative/CD34-negative (Lin(-)CD34(-)) cells in the bone
      marrow of adult mice. The population of Lin(-)CD34(-) in BMCs was isolated by
      magnetic bead sorting and fluorescence-activated cell sorter (FACS) using
      specific lineage (CD4, CD8a, CD11b, CD45R, Gr-1 and TER-119) antibodies and CD34
      antibody. First, we cultured Lin(-)CD34(-) BMCs in the presence of RNIF: vitamin
      A derivative retinoic acid (RA) and neural-inducing factors (platelet-derived
      growth factor BB (PDGF-BB), epidermal growth factor (EGF) and fibroblast growth
      factor-basic (FGF-b)). Analyses of RT-PCR and immunocytochemistry indicated that
      RNIF-treated Lin(-)CD34(-) BMCs expressed neural phenotypes as well as neurogenic
      transcription factors. When we implanted the Lin(-)CD34(-) BMCs isolated from
      enhanced green fluorescent protein (eGFP) transgenic mice into the subventricular
      zone (SVZ) of postnatal mice, eGFP-positive cells survived 3 weeks after the
      injection in the various brain regions, some of which expressed the neural
      phenotypes. Our data suggest that certain subsets in the CD34(-) populations of
      adult bone marrow could have the capacity to differentiate into neural cells in a
      suitable environment.

PMID- 16997467
TI  - Association between apolipoprotein E polymorphism and serum lipid and
      apolipoprotein levels with Alzheimer's disease.
AB  - We have recently demonstrated that apolipoprotein E (APOE)-varepsilon4 allele is
      a risk factor for Alzheimer disease (AD) in Tehran, Iran. The current study
      specifically aimed to examine whether APOE polymorphism in association with serum
      lipids-apolipoprotein level is a risk factor for AD in a population from Tehran,
      Iran. APOE polymorphism and plasma lipids, apoA1, apoB and lipoprotein (a)
      (Lp(a)) levels were determined in 94 AD patients and 111matched controls. Our
      study demonstrated a significant association between APOE polymorphism and the
      level of plasma lipids and apolipoprotein with AD in this population. The AD
      subjects had significantly lower apoA1 (p<0.001) and HDL-C (p<0.01) and higher
      apoB (p=0.01) and LDL-C (p=0.02) levels than that of the control group. The AD
      subjects carrying APOE-varepsilon4 allele had lower plasma apoA1 (t=5.2, p<0.002)
      and HDL-C level (t=2.7, p=0.01) but had higher plasma apoB (t=-5.4, p<0.002), LDL
      C (t=-4.6, p=0.005) and total cholesterol (TC) (t=-2.7, p=0.01) than that of the
      non APOE-varepsilon4 carriers. These results indicated that AD patients with APOE
      varepsilon4 allele has a distinct plasma lipid profile and carrier of this allele
      with low levels of apoA1 and HDL-C may be more susceptible to AD.

PMID- 16997468
TI  - Determining behavioural and physiological responses to pain in infants at risk
      for neurological impairment.
AB  - Multiple researchers have validated indicators and measures of infant pain.
      However, infants at risk for neurologic impairment (NI) have been under studied.
      Therefore, whether their pain responses are similar to those of other infants is
      unknown. Pain responses to heel lance from 149 neonates (GA>25-40 weeks) from 3
      Canadian Neonatal Intensive Care units at high (Cohort A, n=54), moderate (Cohort
      B, n=45) and low (Cohort C, n=50) risk for NI were compared in a prospective
      observational cohort study. A significant Cohort by Phase interaction for total
      facial action (F(6,409)=3.50, p=0.0022) and 4 individual facial actions existed;
      with Cohort C demonstrating the most facial action. A significant Phase effect
      existed for increased maximum Heart Rate (F(3,431)=58.1, p=0.001), minimum Heart
      Rate (F(3,431)=78.7, p=0.001), maximum Oxygen saturation (F(3,425)=47.6,
      p=0.001), and minimum oxygen saturation (F(3,425)=12.2, p=0.001) with no Cohort
      differences. Cohort B had significantly higher minimum (F(2,79)=3.71, p=0.029),
      and mean (F(2,79)=4.04, p=0.021) fundamental cry frequencies. A significant Phase
      effect for low/high frequency Heart Rate Variability (HRV) ratio (F(2,216)=4.97,
      p=0.008) was found with the greatest decrease in Cohort A. Significant Cohort by
      Phase interactions existed for low and high frequency HRV. All infants responded
      to the most painful phase of the heel lance; however, infants at moderate and
      highest risk for NI exhibited decreased responses in some indicators.

PMID- 16997469
TI  - NMDA receptor-mediated activation of medullary pro-nociceptive neurons is
      required for secondary thermal hyperalgesia.
AB  - There is now direct evidence that a class of neurons in the rostral ventromedial
      medulla (RVM) exerts a net facilitatory influence on spinal nociception. The
      present experiments were designed to test whether activation of these neurons,
      referred to as "on-cells", is required as part of a positive feedback loop
      leading to secondary hyperalgesia in acute inflammation produced by topical
      application of mustard oil. Activity of a characterized RVM neuron and paw
      withdrawals to heat (plantar surface) were recorded in barbiturate-anesthetized
      rats. Following three baseline trials, mustard oil was applied to the skin above
      the knee. Cell activity and paw withdrawal latencies were monitored for an
      additional 45min. Application of mustard oil produced an increase in on-cell
      discharge that was associated with a substantial decrease in withdrawal latency
      of the ipsilateral paw. Blocking on-cell activation using local infusion of the
      NMDA-receptor antagonist AP5 into the RVM prevented hyperalgesia. Secondary
      thermal hyperalgesia following mustard oil was also associated with a significant
      decrease in the firing of "off-cells", a cell population thought to exert a net
      inhibitory influence on nociception. Depression of off-cell firing was unaffected
      by AP5 microinjection. The firing of "neutral cells", which have no documented
      role in nociceptive modulation, was unchanged following mustard oil and also
      unaffected by AP5 infusion in the RVM. Brainstem descending controls are
      receiving increasing attention in efforts to understand hyperalgesia and
      persistent pain states. The present experiments demonstrate that a novel, NMDA
      mediated activation of on-cells is required for secondary thermal hyperalgesia in
      acute inflammation.

PMID- 16997470
TI  - To what extent do we share the pain of others? Insight from the neural bases of
      pain empathy.

PMID- 16997471
TI  - Catecholamine-induced excitation of nociceptors in sympathetically maintained
      pain.
AB  - Sympathetically maintained pain could either be mediated by ephaptic interactions
      between sympathetic efferent and afferent nociceptive fibers or by catecholamine
      induced activation of nociceptive nerve endings. We report here single fiber
      recordings from C nociceptors in a patient with sympathetically maintained pain,
      in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both
      legs. We classified eight C-fibers as mechano-responsive and six as mechano
      insensitive nociceptors according to their mechanical responsiveness and activity
      dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/
      2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of
      several seconds following strong endogenous sympathetic bursts; they were also
      excited for about 3 min following the injection of norepinephrine (10 microl,
      0.05%) into their innervation territory. In these two fibers, a prolonged
      activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl)
      and sensitization of their heat response following prostaglandin E2 injection
      were recorded, evidencing their afferent nature. Moreover, their activity
      dependent slowing was typical for mechano-insensitive nociceptors. We conclude
      that sensitized mechano-insensitive nociceptors can be activated by endogenously
      released catecholamines and thereby may contribute to sympathetically maintained
      pain. No evidence for ephaptic interaction between sympathetic efferent and
      nociceptive afferent fibers was found.

PMID- 16997472
TI  - Higher levels of pain readiness to change and more positive affect reduce pain
      reports--a weekly assessment study on arthritis patients.
AB  - The objective of the study was to analyze the relationships between Pain
      Readiness to Change, weekly measures of positive and negative affect and pain
      over eight subsequent weeks in patients with rheumatoid arthritis (RA). Factor
      analysis based on data from three different samples of patients with rheumatic
      diseases and other chronic pain conditions suggested a three factor solution for
      the Norwegian version of the Pain Stages of Change questionnaire (PSOCQ)
      representing Precontemplation, Contemplation, and Action/Maintenance (ACT) stages
      from the original Transtheoretical Model. Multilevel analyses on the weekly
      assessed data from a sub sample of 40 patients with RA revealed that higher
      levels of Pain Readiness to Change represented by high ACT scores were associated
      with more positive affect from week to week while no association was found
      between Readiness to Change and weekly pain. However, there was an interaction
      effect between Pain Readiness to Change and weekly positive affect on weekly
      pain, indicating that those persons having a higher level of Readiness to Change
      reported less pain in weeks when they also experienced increased positive affect.
      This may imply that a combination of cognitive factors and positive affect is
      most effective in relation to pain reduction. Results encourage continued
      investigation of apparent interactions between chronic pain, affect, and pain
      self-management.

PMID- 16997473
TI  - Infectivity and pathogenicity of Cryptosporidium andersoni to a novel host,
      southern multimammate mouse (Mastomys coucha).
AB  - The infectivity and pathogenicity of Cryptosporidium andersoni (bovine isolate)
      for neonatal and adult southern multimammate mice (Mastomys coucha) was studied
      using transmission experiments. C. andersoni isolate used in this study was not
      infective for BALB/c mice, but experimental infection proved susceptibility of
      neonatal and adult M. coucha to the infection. The prepatent period was 20-24
      days, the patent period varied between 46 and 59 days. No signs of clinical
      illness or macroscopic findings were detected in infected animals.
      Cryptosporidium developmental stages were detected only in the glandular part of
      the stomach of M. coucha in histological sections stained with Wolbach's
      modification of Giemsa and using immunofluorecence. Histopathological changes
      were characterized by dilatation and epithelial metaplasia of infected gastric
      glands without inflammatory response in the lamina propria. Neonatal M. coucha
      were more susceptible to C. andersoni infection than adults. M. coucha seems to
      be a useful laboratory model for study of C. andersoni infection.

PMID- 16997474
TI  - Neospora caninum detected in feral rodents.
AB  - The role of rodents in the epidemiology of neosporosis was investigated by
      assaying brain tissue of feral mice (Mus musculus) and rats (Rattus norvegicus)
      for Neospora caninum. Both mouse and rat brain tissue were extracted for total
      DNA, and subjected to two different N. caninum-specific nested polymerase chain
      reaction (PCR) assays. A portion of brain tissue from the mice and rats were also
      assayed for N. caninum in gerbils or gamma-interferon gene knockout (KO) mice. Of
      the 105 feral mice tested, 10% were positive in the N. caninum-specific PCR
      assays. Of the 242 rats tested, 30% were positive in both assays. Although mice
      and rats had N. caninum by PCR testing, clinical signs of N. caninum infection
      were not observed nor were N. caninum parasites observed in gerbils or KO mice
      inoculated with the rodent brain tissue.

PMID- 16997475
TI  - Unprecedented dual binding behaviour of acridine group of dye: a combined
      experimental and theoretical investigation for the development of anticancer
      chemotherapeutic agents.
AB  - Acridine group of dyes are well known in the field of development of probes for
      nucleic acid structure and conformational determination because of their
      relevance in the development of novel chemotherapeutic agents, footprinting
      agents and for gene manipulation in biotechnology and medicine. Here, we report
      the interaction of 9-N,N-dimethylaniline decahydroacridinedione (DMAADD), a new
      class of dye molecule with calf thymus DNA (CT-DNA) which has been studied
      extensively by means of traditional experimental and theoretical techniques. The
      changes in the base stacking of CT-DNA upon the binding of DMAADD are reflected
      in the circular dichroic (CD) spectral studies. Competitive binding study shows
      that the enhanced emission intensity of ethidium bromide (EB) in presence of DNA
      was quenched by the addition of DMAADD indicating that it displaces EB from its
      binding site in DNA and the apparent binding constant has been estimated to be
      (3.3+/-0.2)x10(5) M(-1). This competitive binding study and further fluorescence
      experiments reveal that DMAADD is a moderate binder of CT-DNA, while viscosity
      measurements show that the mode of binding is partial intercalation. Generally,
      one would expect increase in the melting temperature (T(m)) of DNA in presence of
      intercalators. Interestingly, an unusual decrease in melting temperature
      (DeltaT(m) of -4+/-0.2 degrees C) of DNA by the addition of DMAADD was observed.
      From our knowledge such a decreasing trend in melting point was not reported
      before for all the possible modes of binding. Molecular modeling gave the
      pictorial view of the binding model which clearly shows that of the various mode
      of binding, the dye prefers the major groove binding to the sites rich in GC
      residues and to the sites rich in AT residues it prefers intercalation mode of
      binding either through major or minor groove with the inclusion of the N,N
      dimethylaniline (DMA) group inside the double helix which has been stacked in
      between the bases, under physiological relevant pH of 7.5.

PMID- 16997476
TI  - Aetiology and outcome of burns in the elderly.
AB  - INTRODUCTION: This retrospective study, analyses aetiology and factors affecting
      the outcome of burns in patients over 65 years of age. METHODS: Sixty-three
      consecutive patients, over 65 years of age, were admitted to a Burns Unit over a
      period of 3 years. Retrospective data was analyzed, taking into account
      aetiology, burn thickness and area, co-morbid factors. Also, surgery as a factor
      affecting outcome was examined. RESULTS: There was a significant difference of
      total body surface area burn (TBSA), Abbreviated Burn Severity Index (ABSI), Baux
      score and the number of pre-existing co-morbid factors between survivors and non
      survivors. Age and surgery were not significant to the outcome. Patients
      undergoing surgery had increased hospital stay without any difference in
      mortality. The timing of surgery did not have any impact on hospital stay or
      survival. CONCLUSION: This study shows a positive correlation between the number
      of co-morbid conditions and mortality. Early surgery after careful patient
      selection does not have any negative impact on patient survival.

PMID- 16997477
TI  - The high-density foam aeroplane splint: a modified approach to the treatment of
      axilla burns.
AB  - Axillary burns and contractures are physically debilitating. Early splinting and
      patient compliance is crucial to maximise functional outcomes. Traditional
      treatment of axillary contractures involves fabrication of thermoplastic
      aeroplane splints. However, thermoplastic splints can be time consuming to
      fabricate, heavy, uncomfortable and difficult to don by patients and family. Due
      to these problems a modified high-density foam (HDF) aeroplane splint was
      designed. The purpose of designing a different type of aeroplane splint was to
      increase compliance, comfort and ease of use for health professionals, patients
      and family, and to decrease fabrication time.

PMID- 16997478
TI  - Protection of skin grafts to the penile shaft using a novel manipulation of
      Allevyn dressing--case report of an alkali burn.

PMID- 16997479
TI  - A new tool for the operating surgeon: a Bluetooth mobile phone headset.

PMID- 16997480
TI  - Use of Transcyte and dermabrasion to treat burns reduces length of stay in burns
      of all size and etiology.
AB  - BACKGROUND: With the cost of healthcare increasing, greater emphasis is placed on
      finding better ways to manage burn patients by increasing the quality of care
      while reducing length of hospital stay (LOS), thereby reducing overall cost. To
      date, this is the largest study to determine if Transcyte reduces LOS for partial
      thickness burns of any size or etiology. METHODS: All consecutive patients with
      deep partial thickness burns from April 2002 to December 2002 were reviewed
      (n=110) with IRB approval. Ninety-two patients were treated with dermabrasion and
      Transcyte only. Eighteen patients were treated with a combination of STSG and
      dermabrasion and Transcyte where appropriate. Our data was compared to the
      American Burn Association Patient Registry, as reported by Saffle et al. 1995.
      RESULTS: The data for percent TBSA and LOS are reported as mean+/-S.E.M. One
      tailed t-test was used to analyze the data. Significant difference was found in
      patients who were treated with dermabrasion and Transcyte compared to the
      population reported by Saffle et al. Patients with 0-19.9% TBSA burn treated with
      dermabrasion and Transcyte had LOS of 6.1 days versus 9.0 days (p<0.001). Those
      with 20-39.9% TBSA burn had length of stay of 17.5 days versus 25.5 days.
      Patients treated with STSG and Transcyte who had 40-59.9% TBSA burn had length of
      stay of 39.7 days versus 44.6 days. Those treated with dermabrasion and Transcyte
      alone had length of stay of 31 days. CONCLUSION: This is the first study
      comparing burns of all sizes treated with dermabrasion and Transcyte with a known
      population receiving standard therapy. The authors found this new method of
      managing patients with partial thickness burns to be more efficacious and
      significantly reduces length of stay compared to traditional management.

PMID- 16997481
TI  - Are burns photographs useful?
AB  - Routine photography of all patients admitted to the West of Scotland Regional
      Burns Unit was introduced in 2003. To date, there are few burns units to evaluate
      the usefulness of photographs taken. AIM: To assess the usefulness of photographs
      of patients admitted to the burns unit to various members of the
      multidisciplinary team. METHOD: A questionnaire was completed by hospital staff
      involved in the management of burns patients over a 3-month period. A total of 43
      questionnaires were completed. RESULTS: The majority of questionnaires were
      completed by nursing staff (55%) followed by medical staff (23%); physiotherapy
      (5%); anaesthetists (7%); theatre staff (5%); students (2%); dietician (2%).
      About 98% of respondents agreed that photographs were useful overall,
      particularly for teaching purposes. About 9% disagreed that photographs were
      useful for assessment due to difficulty in assessing depth of burn. About 72%
      agreed that the photographs were useful for patient management and improve
      patient care. About 88% agreed that all patients should have photographs
      available in future. Advantages of photographs include; moving and handling of
      patients; patient positioning in theatre; reviewing wound healing and
      complications. They are useful for assessing site, size and type of burn.
      Disadvantages include difficulty in assessing depth of burn, technical factors,
      and unavailability out of hours. CONCLUSIONS: Photographs of burns patients are
      useful overall to all members of the multidisciplinary team.

PMID- 16997482
TI  - Burn depths evaluation based on active dynamic IR thermal imaging--a preliminary
      study.
AB  - Proper diagnostic assessment of burn wound depth is of the highest importance in
      selecting the mode of burn wound treatment. Several diagnostic methods--clinical
      and histopathological evaluation, as well as methods employing IR imaging--static
      thermography and active dynamic thermography (ADT)--are compared on the basis of
      in vivo experiments conducted on three domestic pigs (23 burn wounds). ADT is
      presented here as a new, reliable and quantitative method of assessing burn wound
      depth on the basis of discrimination of the thermal properties of burnt tissue.
      In the case of ADT registration of thermal images was performed following thermal
      pulse excitation. A series of captured infrared images was used as the basis for
      calculating the thermal time constant tau for each pixel. The parameter values
      were compared with histopathological and clinical assessments of burn depth. The
      mean value of tau was found for burns, which heal within 3 weeks (tau=12.08+/
      1.94s) and for burns, which did not heal during this period (tau=9.07+/-0.68s),
      p<0.05. The accuracy, sensitivity and specificity of all the methods tested were
      compared, the best results coming from ADT. The ADT method is fast, non-invasive
      and relatively inexpensive, although it still requires further animal
      experimentation as well as clinical study to confirm the results.

PMID- 16997483
TI  - Evidence for a distinct group of nestin-immunoreactive neurons within the basal
      forebrain of adult rats.
AB  - Nestin is an intermediate filament protein serving as a marker for
      neuroprogenitor and stem cells. Here we report that a cluster of previously
      unrecognized nestin immunoreactive (nestin-ir) neurons was located in the medial
      septum-diagonal band of Broca (MS-DBB) of the basal forebrain in adult rats.
      Nestin-ir neurons were exclusively located in the MS-DBB and intermingled with
      choline acetyltransferase-ir (ChAT-ir), parvalbumin-ir (PV-ir), or nicotinamide
      adenine dinucleotide phosphate (NADPH)-diaphorase reactive (NADPHd-reactive)
      neurons. However, there was no colocalization between nestin-ir and PV-ir in
      single neurons in MS-DBB; only about 35% of nestin-ir neurons were ChAT-ir, and
      8%-12% of nestin-ir neurons were NADPHd-reactive. Morphologically, nestin-ir
      neurons showed a larger size of somata than that of ChAT-ir or PV-ir neurons and
      the distribution of nestin-ir neurons spread across the rostro-caudal extent of
      the MS-DBB. Moreover, retrograde tracing revealed that a significant portion of
      these nestin-ir neurons projected to the thalamus and hippocampus. These results,
      for the first time, provide strong evidence that there exists a cluster of
      previously unrecognized nestin-ir neurons in MS-DBB of the basal forebrain in
      adult rats and that these nestin-ir neurons are distinguishable from ChAT-ir, PV
      ir, and NADPHd-reactive neurons.

PMID- 16997484
TI  - Differential regulation of transport proteins in the periinfarct region following
      reversible middle cerebral artery occlusion in rats.
AB  - Members of various transport protein families including ATP-binding cassette
      transporters and solute carriers were shown to be expressed in brain capillaries,
      choroid plexus, astrocytes or neurons, controlling drug and metabolite
      distribution to and from the brain. However, data are currently very limited on
      how the expression of these transport systems is affected by damage to the brain
      such as stroke. Therefore we studied the expression of four selected
      transporters, P-glycoprotein (Mdr1a/b; Abcb1a/b), Mrp5 (Abcc5), Bcrp (Abcg2), and
      Oatp2 (Slc21a5) in a rat model for stroke. Transporter expression was analyzed by
      real-time polymerase chain reaction in the periinfarcted region and protein
      localization and cellular phenotyping were done by immunohistochemistry and
      confocal immunofluorescence microscopy. After stroke, P-glycoprotein staining was
      detected in endothelial cells of disintegrated capillaries and by day 14 in newly
      generated blood vessels. There was no significant difference, however, in the
      Mdr1a mRNA amount in the periinfarcted region compared with the contralateral
      site. For Bcrp, a significant mRNA up-regulation was observed from days 3-14.
      This up-regulation was followed by the protein as confirmed by quantitative
      immunohistochemistry. Oatp2, located in the vascular endothelium, was also up
      regulated at day 14. For Mrp5, an up-regulation was observed in neurons in the
      periinfarcted region (day 14). In conclusion, after stroke the transport proteins
      were up-regulated with a maximum at day 14, a time point that coincides with
      behavioral recuperation. The study further suggests Bcrp as a pronounced marker
      for the regenerative process and a possible functional role of Mrp5 in surviving
      neurons.

PMID- 16997485
TI  - Munc18-1 phosphorylation by protein kinase C potentiates vesicle pool
      replenishment in bovine chromaffin cells.
AB  - Activation of protein kinase C (PKC) after robust stimulation is necessary for
      vesicle pool replenishment in secretory cells. Here we studied the contribution
      of a prominent downstream PKC target, Munc18-1, to this process in bovine
      chromaffin cells. In these cells, both activation of endogenous PKC and
      overexpressing of Munc18-1 promote vesicle pool replenishment after an extensive
      stimulation. In order to study the physiological relevance of PKC-dependent
      Munc18-1 phosphorylation, we generated two Munc18-1 phospho-mutants; one that
      mimics a constitutively PKC-phosphorylated Munc18-1 (i.e. a phosphomimetic
      mutant; Munc18-1(S313D)) and a second that cannot be PKC-phosphorylated (Munc18
      1(3A)). Overexpression of Munc18-1(3A) caused a significant decrease in vesicle
      pool replenishment following a depleting stimulation, while Munc18-1(S313D)
      caused a significant increase in vesicle pool replenishment. These findings
      suggested that the phosphorylation of Munc18-1 by PKC potentiates vesicle pool
      replenishment. This hypothesis was further strengthened by the finding that
      overexpression of wild type Munc18-1 in the presence of a PKC inhibitor caused a
      significant reduction in vesicle pool replenishment, similar to that observed
      with Munc18-1(3A). Moreover, overexpression of Munc18-1(S313D) in the presence of
      the PKC inhibitor partly alleviated this attenuation, elucidating Munc18-1's
      unique contribution to vesicle pool replenishment. Finally, we demonstrate that
      Munc18-1 promotes vesicle docking in a phosphorylation-independent manner. This
      is deduced from the findings that both the wild type and the two Munc18-1 phospho
      mutants enhanced docking to the same extent in bovine chromaffin cells. We
      conclude that Munc18-1 facilitates docking in a PKC phosphorylation-independent
      manner, and that its phosphorylation by PKC potentiates vesicle pool
      replenishment following a depleting stimulation, at a post-docking stage.

PMID- 16997486
TI  - Cathepsin D-mediated proteolysis of apolipoprotein E: possible role in
      Alzheimer's disease.
AB  - Proteolysis of apolipoprotein E (apoE) may be involved in the pathogenesis of
      Alzheimer's disease (AD). We previously identified aspartic protease(s) as
      possibly contributing to the proteolysis of apoE in human brain homogenates. The
      current study used biochemical and immunohistochemical methods to examine whether
      cathepsin D (catD) and cathepsin E (catE), candidate aspartic proteases, may be
      involved in apoE proteolysis. CatD was found to proteolyze both lipid-free
      recombinant full-length human apoE and lipidated human plasma full-length apoE
      (apoE4/dipalmitoylphosphatidylcholine-reconstituted discs). CatE was found to
      proteolyze lipid-free recombinant human apoE to a much greater extent than
      lipidated apoE. This proteolysis, as well as proteolysis of human apoE added to
      brain homogenates from apoE-deficient mice, was inhibited by pepstatin A (an
      aspartic protease inhibitor), but not by phenylmethanesulfonyl fluoride (a serine
      protease inhibitor). The major apoE fragment obtained with catD included the
      receptor-binding domain and had an apparent molecular weight similar to that
      found in human brain homogenates. There was little immunoreactivity for catE in
      AD brain tissue sections. In contrast, qualitative and quantitative analyses of
      immunostained sections of the frontal cortex revealed that catD and apoE are
      colocalized in a subset of predominantly dense-core neuritic plaques and in some
      neurofibrillary tangles. A positive correlation was observed between estimated
      duration of illness and the percentage of apoE-positive plaques that were also
      catD-positive. These results suggest that aspartic proteases, catD in particular,
      may be involved in proteolysis of apoE and perhaps contribute to the generation
      of apoE fragments previously implicated in AD pathology.

PMID- 16997487
TI  - Cardiovascular actions of adrenocorticotropin microinjections into the nucleus
      tractus solitarius of the rat.
AB  - The presence of adrenocorticotropin (ACTH) containing cells and melanocortin (MC)
      receptors has been reported in the nucleus tractus solitarius (NTS) of the rat.
      The importance of the NTS in the regulation of cardiovascular function is also
      well established. Based on these reports, it was hypothesized that ACTH acting
      within the NTS may modulate the central regulation of cardiovascular function. To
      test this hypothesis, cardiovascular effects of ACTH in the NTS were investigated
      in intact urethane-anesthetized and unanesthetized decerebrate, artificially
      ventilated, adult male Wistar rats. Microinjections of ACTH (0, 0.5, 1, 2, and 4
      mM) into the medial subnucleus of NTS (mNTS) elicited decreases in mean arterial
      pressure (MAP; 0+/-0, 24.4+/-3.5, 35.7+/-4.3, 44.5+/-5.8 and 53.7+/-5.6 mm Hg,
      respectively) and heart rate (HR; 0+/-0, 25.7+/-5.3, 35.5+/-6.4, 47.5+/-12.1 and
      55.0+/-5.6 beats/min, respectively). The onset and duration of the responses to
      microinjections of ACTH (0.5-4 mM) were 5-10 s and 45-120 s, respectively.
      Control microinjections of artificial cerebrospinal fluid (aCSF) did not elicit
      any response. The volume of all microinjections was 100 nl. The concentrations of
      ACTH that elicited depressor and bradycardic responses when microinjected into
      the mNTS (e.g. 1 or 2 mM, 100 nl), did not elicit a response when injected i.v.
      (n=5) or i.c.v. (n=2) indicating that there was no leakage of the drug from the
      injection site in the mNTS. Microinjections of MC3/4 receptor antagonists (acetyl
      [Nle(4), Asp(5), d-2-Nal(7), Lys(10)]-cyclo-alpha-MSH amide, fragments 4-10
      (SHU9119) and agouti-related protein (83-132) amide) into the mNTS blocked the
      responses to ACTH. Microinjections of ACTH (2 mM) into the mNTS decreased
      efferent greater splanchnic nerve activity. Bilateral vagotomy significantly
      attenuated ACTH-induced bradycardia. These results indicated that: 1)
      microinjections of ACTH into the mNTS elicited depressor and bradycardic
      responses, 2) these responses were mediated via MC3/4 receptors, 3) the depressor
      effects were mediated via a decrease in the activity of the sympathetic nervous
      system, and 4) the bradycardic responses were vagally mediated.

PMID- 16997488
TI  - Upregulation of retinal transglutaminase during the axonal elongation stage of
      goldfish optic nerve regeneration.
AB  - Fish CNS neurons can repair their axons following nerve injury, whereas mammalian
      CNS neurons cannot regenerate, and become apoptotic within 1-2 weeks after the
      nerve lesion. One explanation for these differences is that one, or several
      molecules are upregulated in fish CNS neurons during nerve regeneration, and this
      same molecule is downregulated in mammalian CNS neurons before the development of
      apoptosis caused by nerve injury. A molecule satisfying these criteria might
      successfully rescue and repair the mammalian CNS neurons. In this study, we
      looked for such a candidate molecule from goldfish retinas. Transglutaminase
      derived from goldfish retina (TG(R)) was characterized as a regenerating molecule
      after optic nerve injury. A full-length cDNA for TG(R) was isolated from the
      goldfish retinal cDNA library prepared from axotomized retinas. Levels of TG(R)
      mRNA and protein increased only in the retinal ganglion cells (RGCs) between 10
      and 40 days after optic nerve transection. Recombinant TG(R) protein enhanced
      neurite outgrowth from adult fish RGCs in culture. Specific interference RNA and
      antibodies for TG(R) inhibited neurite outgrowth both in vitro and in vivo. In
      contrast, the level of TG(R) protein decreased in rat RGCs within 1-3 days after
      nerve injury. Furthermore, the addition of recombinant TG(R) to retinal cultures
      induced striking neurite outgrowth from adult rat RGCs. These molecular and
      cellular data strongly suggest that TG(R) promotes axonal elongation at the
      surface of injured RGCs after optic nerve injury.

PMID- 16997489
TI  - Environmental influences on family similarity in afternoon cortisol levels: twin
      and parent-offspring designs.
AB  - Modest genetic effects on morning, but not late-day, cortisol levels have been
      established. Environmental demands may influence basal cortisol levels later in
      the day. Thus, we anticipated that individuals in the same family would have
      similar afternoon cortisol levels to the extent that they share aspects of their
      environment. We examined afternoon basal cortisol levels measured across 3
      consecutive days in mothers and fathers and in multiple offspring in two separate
      large and longitudinal studies. Study I involved 321 families with singletons
      while study II involved 233 families with twins. Modest family similarity was
      apparent for afternoon basal cortisol levels in both studies. Spouses' cortisol
      levels were also correlated. Data from study II demonstrated that family
      resemblance in afternoon cortisol was accounted for by underlying shared
      environmental factors, but not underlying genetic factors. Shared environment
      accounted for 62% of the variation in twin afternoon basal cortisol levels and
      14% of the variation in parent afternoon basal cortisol levels. We used pooled
      data from the two studies to examine whether parental depression, socioeconomic
      status (SES), and offspring sex and age impacted cortisol levels. Female
      offspring had higher cortisol levels than males, and cortisol decreased with age
      until about 9 years of age, after which cortisol increased with age. Family
      similarity persisted after accounting for parental depression, SES, time of day,
      and offspring sex and age, which suggests that the shared family environment
      influences parent and offspring stress hormone levels throughout the childhood
      years.

PMID- 16997490
TI  - Which dimensions of impulsivity are related to cigarette craving?
AB  - Cigarette smoking is a very important health problem and represents the largest
      preventable risk factor for premature death in developed countries. A
      considerable body of research indicates that impulsivity is a central etiological
      concept in many theoretical models of tobacco addiction. The aim of this study is
      to analyse which dimensions of impulsivity are related to cigarette craving. To
      this end, 40 undergraduate psychology students were screened using the revised
      Questionnaire on Smoking Urges (QSU-12) and the French adaptation of the UPPS
      Impulsive Behavior Scale (UPPS). This scale identifies four distinct components
      associated with impulsive behaviour: urgency, lack of premeditation, lack of
      perseverance, and sensation seeking. The results showed that urgency is a
      significant predictor of tobacco cravings, while depression and anxiety are not.

PMID- 16997491
TI  - Molecular mechanism of nitrogen mustard induced leukocyte(s) chemotaxis.
AB  - Nitrogen mustard(s) (NM) are the primary chemotherapeutic agents (Chlorambucil,
      BSO) that are used in treating the B-cell chronic lymphocyte leukemia (B-CLL). It
      is known that NM imparts oxidative stress by inducing the reactive oxygen species
      (ROS) and reactive nitrogen species (RNS) production in B-lymphocytes of B-CLL.
      It is likely that these nitrogen mustards can cause the oxidative stress in the
      peripheral blood leukocytes (PBL) of B-CLL patients. It is possible that chronic
      exposure of PBL to NM would induce drug resistance in B-CLL patients. However,
      the precise molecular mechanism(s) by which NM affect the PBL are not known at
      present. Here, an effort is made to present plausible mechanisms by which chronic
      NM exposure could lead to increased PBL chemotaxis and vascular tissue damage in
      B-CLL patients The clinical implication of this phenomenon is most likely the
      unwanted organ dysfunction in B-CLL patients. Identification of viable
      therapeutic targets to attenuate the PBL activation during the NM therapy would
      be beneficial for the clinical remission of B-CLL.

PMID- 16997492
TI  - Plasmodium falciparum chloroquine resistance marker protein (Pfcrmp) may be a
      chloroquine target protein in nucleus.
AB  - We previously hypothesized that the key site of chloroquine (CQ) antimalarial
      action and resistance development is in nucleus of malaria parasite, and that
      lysosomal (food vacuolar) accumulation of CQ may benefit parasite's survival
      through reducing the drug pressure on the key site. To further support our
      hypothesis we propose that Plasmodium falciparum chloroquine resistance marker
      protein (Pfcrmp) may be a CQ target protein in nucleus and that CQ resistance in
      malaria parasites may be caused by genetic alterations in Pfcrmp gene.

PMID- 16997493
TI  - Immune response: A possible role in the pathophysiology of hemangioma.
AB  - Hemangioma is a distinct category of benign vascular tumors characterized by
      presentation within the first weeks of life, rapid growth during the first year
      and variable degree of spontaneous involution over a period of several years.
      Recent research reported that CD8+ T cells in hemangiomas, and the endothelia of
      hemangioma uniquely expressed leukocyte marker FCgammaRII and myeloid cell
      marker. Presence of high levels of indoleamine 2,3-dioxygenase in proliferating
      hemangiomas and significantly decreasing during involution was also confirmed.
      Topical application of imiquimod cream, an immune regulator, to proliferating
      hemangiomas apparently accelerated regression of the lesions. These findings
      suggest immune response may be involved in the pathogenesis of hemangioma. The
      endothelia of hemangioma may express various markers to escape the immune
      surveillance. An immune response may be one of the mechanisms for hemangioma
      regression. Strategies with systemically or locally applying immune regulator
      into the tumor may be an applicable way in accelerating the involution of
      hemangioma.

PMID- 16997494
TI  - Could taking an up-elevator on the way to the delivery room be a potential novel
      therapy for dystocia?

PMID- 16997495
TI  - Interleukine-6 (IL-6) may be a link between myasthenia gravis and myoepithelioma
      of the parotid gland.
AB  - Myoepithelioma is a rare benign neoplasm of the salivary glands occurring more
      frequently in the parotids. Myasthenia gravis (MG) is a chronic, T-cell
      dependent, antibody and complement-mediated autoimmune neuromuscular transmission
      disorder. Interleukine-6 (IL-6) is an immune protein belonging to the family of
      the hematopoietins, liberated in response to infection, burns, trauma, and
      neoplastic diseases. It seems that an overproduction of IL-6 might play an
      important role in the pathophysiology of MG. Moreover, it has been discussed the
      possible role of IL-6 as a modulating factor either in proliferation or in
      differentiation of pleomorphic adenoma cell line into myoepithelioma. The authors
      present a rare case of parotid myoepithelioma occurred in a patient affected by
      myasthenia gravis and suppose a possible IL-6 mediated relationship between
      myasthenia gravis and parotid myoepithelioma.

PMID- 16997496
TI  - Covalent attachment of multifunctional chimeric terminal proteins to 5' DNA ends:
      A potential new strategy for assembly of synthetic therapeutic gene vectors.
AB  - The generation of synthetic therapeutic gene vectors requires the coupling of DNA
      to transfer-promoting peptides including cellular receptor ligands, protein
      transduction domains, hydrophobic peptides for attachment to lipid membranes,
      nuclear localisation signals, cytoskeleton attachment motifs, nuclear matrix
      association elements and immune evasion moieties. Existing methods of peptide-DNA
      joining often interfere with transgene expression and, therefore, are inadequate
      for production of effective therapeutic vector complexes, particularly destined
      for gene delivery in the challenging environment in vivo. However, there is a
      natural mechanism for rigid coupling of polypeptides with DNA. Some bacterial and
      eukaryotic linear plasmids, adenoviruses and a number of bacteriophages including
      phi29 of Bacillus subtilis and PRD1 of Escherichia coli use terminal proteins
      covalently bound to 5' DNA ends to prime replication. Inverted terminal DNA
      repeats, normally short DNA sequences, contain all the sequences required in cis
      for the covalent coupling reaction. The complex of the terminal protein, DNA
      polymerase and some known auxiliary proteins supplies sufficient trans-functions,
      thus enabling simple linking of the terminal proteins to DNA in vitro. We
      hypothesise that chimeric fusion proteins, constructed on the basis of terminal
      proteins of adenoviruses, linear plasmids or bacteriophages with protein-primed
      replication, can on the one hand retain the ability to bind covalently 5' DNA
      termini in conditions established previously for protein-primed replication in
      vitro, and on the other hand confer gene transfer facilitating properties and
      enhanced longevity of efficient transgene expression. Terminal localisation of
      the chimeric proteins can ensure that they do not interfere with transgene
      transcription. At the same time a covalent bond between polypeptide and DNA can
      provide rigid coupling ensuring their stable association en route to nuclei.
      Bound to 5'-ends of the delivered DNA, terminal protein-based chimeras could also
      protect the vector DNA from 5'-3' and possibly 3'-5' exonuclease attack, thus
      limiting its intracellular degradation and increasing longevity of transgene
      expression. Our hypothesis can be tested by measuring the gene transfer
      efficiency of the novel complexes containing linear DNA fragments with covalently
      linked multifunctional chimeric terminal proteins, using previously described
      synthetic gene vectors as standards.

PMID- 16997497
TI  - Neurocognitive deficits in major depression and a new theory of ADHD: a model of
      impaired antagonism of cholinergic-mediated prepotent behaviours in monoamine
      depleted individuals.
AB  - The study builds on the propositions introduced in a companion paper on the
      neuropharmacology of cognition and its relation to key findings in psychiatry.
      Cognitive inhibition is often invoked to explain performance in psychiatric
      illness. Yet it remains only a general conceptual model of executive dysfunction.
      Premotor theory proposes both neuroanatomical and neuropharmacological
      equivalents of conscious and unconscious processes. The interaction between
      monoaminergic and cholinergic neurotransmission is stated to have an inverse
      effect on these two fundamental psychological processes. If one conceives of
      cognitive inhibition as a failure to voluntarily suppress unconscious prepotent
      responses, then a deficit in monoaminergic antagonism of cholinergic facilitated
      prepotent responses accounts for the observed behavioural phenotypes. The
      plasticity of behaviour is further hypothesized to have an equivalent in
      intracellular signalling leading to plastic changes in neural networks. Apart
      from inhibition of prepotent responses it permits the formulation of new
      behavioural phenotypes. At the receptor level Gi-Gq/11 transduction coupling is
      proposed to mediate this effect. A hypofunctioning monoaminergic system is
      thought to underlie the clinical pictures of major depression and ADHD. The
      neurocognitive deficits of depression include memory loss, poor concentration and
      rumination. ADHD is characterized by inattention, impulsivity and hyperactivity.
      Both these syndromes effectively respond to raising serotonin and dopamine
      levels, respectively. The core symptoms can usefully be attributed to an
      imbalance between the neuromodulatory effects of monoamines and ACh. Taking the
      model of monoaminergic-muscarinic receptor interactions presented previously and
      extended here, a new hypothesis is proposed for the core symptoms of ADHD.
      Accordingly, impulsivity and hyperactivity result from impaired dopaminergic
      inhibition and remodelling of muscarinic mediated prepotent responses. The model
      also predicts memory impairment in major depression by proposing that low
      serotonin levels in the neocortex is linked to focal hippocampal dysfunction.
      Hippocampal theta is proposed to trigger phasic monoaminergic activation involved
      in encoding of cortical traces and plasticity of propotent networks. It proposes
      a hypothesis for the enhancement of mood and behaviour induced by antidepressants
      is partly a response to plasticity of neural networks, that is, remodelling of
      cholinergic-mediated negative habitual behaviours.

PMID- 16997498
TI  - The evolutionary biology of cryptic pregnancy: A re-appraisal of the "denied
      pregnancy" phenomenon.
AB  - Previous research on 'denied pregnancy', i.e. lack of subjective awareness of
      pregnancy until the end of gestation in pregnant women, is reviewed and
      reinterpreted in an evolutionary biological framework. Recent epidemiological
      studies show that this condition has a much higher incidence than previously
      thought (about 1:475). Very often, bodily symptoms of pregnancy (nausea,
      amenorrhea and abdomen swelling) are absent or greatly reduced, and neonates tend
      to be underweight; in many cases, pregnancy goes undetected also by relatives and
      physicians. Current explanations in the clinical literature are based on
      psychodynamic hypotheses about pregnancy-related unconscious conflicts; the lack
      of symptoms is accounted for by 'somatic denial'. I argue that such psychodynamic
      accounts are misguided for two reasons: (1) they rest on a failure to recognize
      the active biological role of the fetus in determining the course of pregnancy,
      and (2) they ignore the many levels of mother-fetus conflict over resource
      allocation described by biological theories of parent-offspring conflict. Here I
      propose to redefine this condition as 'cryptic pregnancy', and begin to explore
      its possible physiological correlates and evolutionary significance. In the light
      of parent-offspring conflict theory, cryptic pregnancy appears to reduce the
      costs of pregnancy, both energetic and ecological (mobility, dependence on
      kin/mate, etc.), thus favoring the mother at the expense of the fetus. Reduced
      hCG production and/or effectiveness is likely to be involved in the process. I
      propose and discuss three nonexclusive evolutionary hypotheses to account for
      this phenomenon: (1) cryptic pregnancy could be a nonadaptive outcome of conflict
      resolution processes over resource allocation in pregnancy, possibly related to
      minor disruptions of genomic imprinting mechanisms. (2) Cryptic pregnancy could
      result from missed spontaneous abortions of low-quality fetuses. (3) Finally,
      cryptic pregnancy could be an adaptive pattern of 'forced cooperation' between
      mother and fetus in stressful or threatening ecological circumstances, as
      suggested by the reported association with elevated psychosocial stress. In case
      of reduced survival probability, both mother and fetus would benefit if the
      mother reduced investment in pregnancy in order to maximize her chances of
      surviving and reaching delivery.

PMID- 16997499
TI  - Avian circoviruses of the genus Circovirus: A potential trigger in Pigeon
      breeder's lung (PBL)/Bird fancier's lung (BFL).
AB  - Pigeon breeder's lung (PBL) or Bird fancier's lung (BFL) is one of the most
      common extrinsic allergic alveolitis or hypersensitivity pneumonitis. It is
      caused after prolonged inhalation of avian antigens and provokes a
      hypersensitivity reaction in the lungs of sensitised people. Although the
      pathogenic mechanism is unclear, the epidemiology of BFL shows that it occurs
      worldwide, and has been described in adults keeping birds and also in their
      children. Laboratory findings associated with the disease classified as a type
      III immunologic reaction that produces blood precipitin antibodies against birds'
      serum, feathers, intestinal mucin and/or faeces. In particular, the fine dust
      from pigeon feathers has strong antigenic properties. There is an interaction
      between host and antigen that seems to be influenced by both genetic and
      environmental factors. Avian circoviruses (ACV) of the genus Circovirus, has been
      detected in free-ranging and captive birds worldwide, such as pigeons, canaries,
      psittacines, Senegal doves, finches, gulls, Australian ravens and geese. T
      lymphocytes are the main target cells of the ACV and in the above avian species
      circovirus-like particles were detected in blood, macrophages, feathers, crop
      secretions, intestinal contents and/or faeces. Most of the ACV was demonstrated
      that are pantropic and viral antigen in pigeon tissues was most commonly detected
      in respiratory organs, including the trachea, pharynx and lung. The transmission
      of the circovirus between the birds usually occurs through inhalation of feathers
      dust. There is evidence that animal circoviruses may originate when vertebrates
      become "infected" with DNA from a plant nanovirus. So, it seems that further
      investigation for the avian circoviruses is needed to determine if they are host
      specific or not. This study attempts to demonstrate ACV or ACV-like particles as
      potential triggers in the BFL aetiology, and the possible involvement in BFL's
      pathogenic mechanism.

PMID- 16997500
TI  - Bypassing the learning curve in permanent seed implants using state-of-the-art
      technology.
AB  - PURPOSE: The aim of this study was to demonstrate, based on clinical postplan
      dose distributions, that technology can be used efficiently to eliminate the
      learning curve associated with permanent seed implant planning and delivery.
      METHODS AND MATERIALS: Dose distributions evaluated 30 days after the implant of
      the initial 22 consecutive patients treated with permanent seed implants at two
      institutions were studied. Institution 1 (I1) consisted of a new team, whereas
      institution 2 (I2) had performed more than 740 preplanned implantations over a 9
      year period before the study. Both teams had adopted similar integrated systems
      based on three-dimensional (3D) transrectal ultrasonography, intraoperative
      dosimetry, and an automated seed delivery and needle retraction system (FIRST,
      Nucletron). Procedure time and dose volume histogram parameters such as D90,
      V100, V150, V200, and others were collected in the operating room and at 30 days
      postplan. RESULTS: The average target coverage from the intraoperative plan
      (V100) was 99.4% for I1 and 99.9% for I2. D90, V150, and V200 were 191.4 Gy
      (196.3 Gy), 75.3% (73.0%), and 37.5% (34.1%) for I1 (I2) respectively. None of
      these parameters shows a significant difference between institutions. The
      postplan D90 was 151.2 Gy for I1 and 167.3 Gy for I2, well above the 140 Gy from
      the Stock et al. analysis, taking into account differences at planning, results
      in a p value of 0.0676. The procedure time required on average 174.4 min for I1
      and 89 min for I2. The time was found to decrease with the increasing number of
      patients. CONCLUSION: State-of-the-art technology enables a new brachytherapy
      team to obtain excellent postplan dose distributions, similar to those achieved
      by an experienced team with proven long-term clinical results. The cost for
      bypassing the usual dosimetry learning curve is time, with increasing team
      experience resulting in shorter treatment times.

PMID- 16997501
TI  - Twenty-year incidence and patterns of contralateral breast cancer after breast
      conservation treatment with radiation.
AB  - PURPOSE: This study was undertaken to determine the incidence of contralateral
      breast cancer (CLB) after treatment for early-stage breast cancer with breast
      conserving treatment (BCT), and to observe patterns of CLB presentation. METHODS:
      Medical records of 1,801 women treated for unilateral AJCC Stage 0-II breast
      cancer with BCT between 1977 and 2000 were analyzed as a retrospective cohort.
      RESULTS: The incidence of any CLB at 20 years was 15.4%. The annual risk of
      developing any CLB remained constant at approximately 0.75% per year after
      treatment. The median time to any CLB was 8.2 years (range, 0.5-26.5 years). No
      difference in incidence of CLB was demonstrated in patients with primary invasive
      carcinoma vs. DCIS (p = 0.84). The majority of patients (83%) developing CLB
      tumors developed invasive disease. The risk of developing an invasive CLB did not
      differ significantly for patients with DCIS vs. those with primary invasive
      carcinoma (p = 0.20). The method of detection of the primary tumor (mammography
      vs. physical examination) was not predictive of detection of the CLB (p = 0.20).
      Finally, the location of CLB tumors was not affected by that of prior tumors (p =
      0.82). CONCLUSIONS: The risk of development of CLB persists for at least 20 years
      after treatment for early-stage breast cancer. CLB tumors are frequently
      invasive, and their location is not influenced by location of prior tumors.
      Mammography and physical examination remain essential after BCT for detection of
      a contralateral breast cancer, regardless of the method of detection of the
      primary tumor.

PMID- 16997502
TI  - High-dose-rate (HDR) brachytherapy for the treatment of benign obstructive
      endobronchial granulation tissue.
AB  - BACKGROUND: Severe airway obstruction can occur in the setting of benign
      granulation tissue forming at bronchial anastomotic sites after lung
      transplantation in up to 20% of patients. Many of these benign lesions respond to
      stent placement, laser ablation, or balloon bronchoplasty. However, in certain
      cases, proliferation of granulation tissue may persist despite all therapeutic
      attempts. This study describes a series of refractory patients treated with high
      dose-rate (HDR) brachytherapy for benign proliferation of granulation tissue,
      causing airway compromise. METHODS AND MATERIALS: Between April 2002 and June
      2005, 5 patients with significant airway compromise from recurrent granulation
      tissue were treated with HDR brachytherapy. All patients had previously failed to
      maintain a patent airway despite multiple bronchoscopic interventions. Treatment
      was delivered using an HDR brachytherapy afterloader with (192)Ir. Dose
      prescription was to a depth of 1 cm. All patients were treated weekly, with total
      doses ranging from 10 Gy to 21 Gy in two to three fractions. RESULTS: The median
      follow-up was 12 months. All patients experienced a reduction in therapeutic
      bronchoscopic procedures after HDR brachytherapy compared with the pretreatment
      period. With the exception of possible radiation-induced bronchitis in 1 patient,
      there were no other treatment related complications. At the time of this report,
      2 patients have died and the other 3 are alive with marked symptomatic
      improvement and reduced bronchoscopic procedures. CONCLUSION: High-dose-rate
      brachytherapy is an effective treatment for benign proliferation of granulation
      tissue causing airway obstruction. The early response to therapy is encouraging
      and further follow-up is necessary to determine long-term durability and late
      effects.

PMID- 16997503
TI  - Analysis of clinical and dosimetric factors associated with treatment-related
      pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC) treated
      with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D
      CRT).
AB  - PURPOSE: To investigate factors associated with treatment-related pneumonitis in
      non-small-cell lung cancer patients treated with concurrent chemoradiotherapy.
      PATIENTS AND METHODS: We retrospectively analyzed data from 223 patients treated
      with definitive concurrent chemoradiotherapy. Treatment-related pneumonitis was
      graded according to Common Terminology Criteria for Adverse Events version 3.0.
      Univariate and multivariate analyses were performed to identify predictive
      factors. RESULTS: Median follow-up was 10.5 months (range, 1.4-58 months). The
      actuarial incidence of Grade > or =3 pneumonitis was 22% at 6 months and 32% at 1
      year. By univariate analyses, lung volume, gross tumor volume, mean lung dose,
      and relative V5 through V65, in increments of 5 Gy, were all found to be
      significantly associated with treatment-related pneumonitis. The mean lung dose
      and rV5-rV65 were highly correlated (p < 0.0001). By multivariate analysis,
      relative V5 was the most significant factor associated with treatment-related
      pneumonitis; the 1-year actuarial incidences of Grade > or =3 pneumonitis in the
      group with V5 < or =42% and V5 >42% were 3% and 38%, respectively (p = 0.001).
      CONCLUSIONS: In this study, a number of clinical and dosimetric factors were
      found to be significantly associated with treatment-related pneumonitis. However,
      rV5 was the only significant factor associated with this toxicity. Until it is
      better understood which dose range is most relevant, multiple clinical and
      dosimetric factors should be considered in treatment planning for non-small-cell
      lung cancer patients receiving concurrent chemoradiotherapy.

PMID- 16997504
TI  - Whole-abdomen radiotherapy for non-Hodgkin's lymphoma using twice-daily
      fractionation.
AB  - PURPOSE: To report the tolerability and efficacy of twice-daily whole-abdomen
      irradiation (WAI) for non-Hodgkin's lymphoma (NHL). METHODS AND MATERIALS: Of 123
      patients treated for NHL with WAI, 37% received previous chemotherapy, 28%
      received WAI as part of comprehensive lymphatic irradiation (CLI), and 32%
      received WAI for palliation. The median dose to the whole abdomen was 25.0 Gy,
      followed by a median tumor boost of 9.8 Gy in 58 patients. Fractionation was 1.0
      Gy once daily (54%) or 0.8 Gy twice daily (46%). Blood counts were measured
      weekly. RESULTS: At a median follow-up of 4.3 years, local control was 72% and
      overall survival was 55% at 5 years. Median time of WAI was 42 days for once
      daily treatment and 32 days for twice-daily treatment. Patients receiving twice
      daily WAI did not have a significantly higher rate of acute side effects (e.g.,
      nausea, diarrhea, platelet or red blood cell toxicity). Overall, acute
      thrombocytopenia was the most frequent side effect of treatment; 24 of 96
      patients (25%) with available hematologic data had Grade 3+ toxicity. There was
      no acute Grade 3 gastrointestinal toxicity and no late small bowel obstruction.
      Multiple regression indicated that patients with four or less involved sites and
      disease size < or =6 cm had improved local control and overall survival.
      CONCLUSIONS: Twice-daily WAI using 0.8 Gy/fraction does not appear to have any
      greater toxicity compared with once-daily treatment using 1 Gy/fraction. Small
      doses per fraction (0.8-1 Gy/fx) are effective, tolerated well in the acute
      setting, and associated with a low rate of late toxicity.

PMID- 16997505
TI  - The impact of axillary lymph nodes removed in staging of node-positive breast
      carcinoma.
AB  - PURPOSE: Number of positive lymph nodes in the axilla and pathologic lymph node
      status (pN) have a great impact on staging according to the current American
      Joint Committee on Cancer staging system of breast carcinoma. Our aim was to
      define whether the total number of removed axillary lymph nodes influences the pN
      and thus the staging. METHODS AND MATERIALS: The records of 798 consecutive
      invasive breast cancer patients with T1-3 tumors and positive axillary lymph
      nodes who underwent modified radical mastectomy between 1999 and 2005 in our
      hospital were reviewed. The total number of removed nodes were grouped, and
      compared with the patient and tumor characteristics and the influence of the
      number of nodes removed on the staging was analyzed. RESULTS: The proportion of
      patients with > or =4 positive nodes (59%), and pN3 status (51%) were the highest
      in the group with 21-25 nodes removed. Compared with patients with 1-20 nodes
      removed, the proportion of patients with > or =4 positive nodes (52%), and pN3
      status (46%) were significantly higher in those with more than 20 nodes removed.
      Although the proportion of Stage IIA and IIB decreased, the proportion of Stage
      IIIA and IIIC increased in patients with >20 nodes removed compared with those
      with 1-20 nodes removed. CONCLUSIONS: In patients with axillary node-positive
      breast carcinoma, staging is highly influenced by total number of removed nodes.
      Levels I-III axillary dissection with more than 20 axillary lymph nodes removed
      could lead to more effective adjuvant chemotherapy and increases substantially
      the proportion of patients to receive radiotherapy.

PMID- 16997506
TI  - Radiotherapy-related typing in 842 patients in canton with nasopharyngeal
      carcinoma.
AB  - PURPOSE: The aim of this study was to propose the clinical radiotherapy-related
      typing and to summarize proportional distribution of radiotherapy-related types
      of nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 842 cases of
      NPC were randomly selected. According to 5-year follow-up results after
      radiotherapy, NPC was subdivided into four types: Type I (no primary and regional
      recurrence and no distant metastasis), Type II (primary or regional recurrence
      and no distant metastasis), Type III (no primary and regional recurrence, and
      distant metastasis), and Type IV (primary or regional recurrence, and distant
      metastasis). Proportion of the four types and relationship between this typing
      and Zhi-guang Xie typing were analyzed. RESULTS: Distribution of radiotherapy
      related types of NPC were 50.6%, 23.2%, 20.7%, and 5.6% for Types I, II, III, and
      IV, respectively. For Types D and AD of Zhi-guang Xie typing system and Stage III
      and IV of the 1992 Fuzhou staging system, the proportion of Type III was greater
      than that of Type II; and for Type A and Stage I and II, there was a larger
      proportion of Type II than that of Type III. CONCLUSION: Radiotherapy-related
      typing, as a new clinical subclassification, could be supplementary for previous
      clinical typing and staging.

PMID- 16997507
TI  - Learning of auditory equivalence classes for vowels by rats.
AB  - Four male Long-Evans rats were trained to discriminate between synthetic vowel
      sounds using a GO/NOGO response choice task. The vowels were characterized by an
      increase in fundamental frequency correlated with an upward shift in formant
      frequencies. In an initial phase we trained the subjects to discriminate between
      two vowel categories using two exemplars from each category. In a subsequent
      phase the ability of the rats to generalize the discrimination between the two
      categories was tested. To test whether rats might exploit the fact that
      attributes of training stimuli covaried, we used non-standard stimuli with a
      reversed relation between fundamental frequency and formants. The overall results
      demonstrate that rats are able to generalize the discrimination to new instances
      of the same vowels. We present evidence that the performance of the subjects
      depended on the relation between fundamental and formant frequencies that they
      had previously been exposed to. Simple simulation results with artificial neural
      networks could reproduce most of the behavioral results and support the
      hypothesis that equivalence classes for vowels are associated with an experience
      driven process based on general properties of peripheral auditory coding mixed
      with elementary learning mechanisms. These results suggest that rats use spectral
      and temporal cues similarly to humans despite differences in basic auditory
      capabilities.

PMID- 16997509
TI  - Multiple regulatory regions and tissue-specific transcription initiation mediate
      the expression of NEMO/IKKgamma gene.
AB  - NEMO/IKKgamma gene, which is responsible of two allelic diseases in human, EDA-ID
      and IP, encodes for a protein with a central regulatory role in the activation of
      the NF-kB pathway. We here provide insights into the molecular mechanism
      governing NEMO/IKKgamma expression. We mapped 4 distinctive NEMO/IKKgamma
      transcription start sites each corresponding to an alternative first exon,
      controlled by two conserved promoters. A distal promoter, named promoter A,
      located 10 kb upstream of the coding region and a proximal promoter, promoter B,
      with strong bi-directional activity driving also the transcription of G6PD gene
      in the opposite direction. The promoter B is housekeeping, it is embedded in a
      CpG island, required for proper expression and it is down-regulated by
      methylation. The promoter A is active in cells of hepatic origin and it directs
      transcription of the main NEMO/IKKgamma 5' UTR alternative transcript in liver,
      which starts at a tissue-specific site. Qualitative and quantitative expression
      analysis revealed that each NEMO/IKKgamma 5' UTR alternative transcript has
      different expression profiles indicating that the control of NEMO/IKKgamma
      expression is mediated through tissue-specific transcription initiation sites and
      multiple regulatory regions.

PMID- 16997508
TI  - Subjective sensitivity to monetary gradients is associated with frontolimbic
      activation to reward in cocaine abusers.
AB  - Drug addiction is characterized by marked disruptions in the ability to process
      reward. Here we evaluated in cocaine addicted and healthy control participants
      the subjective sensitivity to reward gradients and its association with neural
      responses to sustained reward. A self-report questionnaire was used to assess the
      former. A functional magnetic resonance imaging task that utilized monetary
      reward as feedback in a blocked design was used to assess the latter. Results
      revealed that whereas control subjects valued high money more than low money,
      over half of the cocaine addicted subjects valued all monetary amounts equally.
      This compromised subjective sensitivity to gradients in reward value was
      significantly correlated with higher activations to money in the lateral
      orbitofrontal cortex/inferior frontal gyrus (BA 47) and amygdala, and lower
      activations in the middle frontal gyrus (BA 6), which together explained 85% of
      the variability on this rating scale in the cocaine abusers only. These results
      provide for the first time evidence of restricted subjective sensitivity to
      gradients of reward in cocaine addiction and of the involvement of frontolimbic
      brain regions (including the orbitofrontal cortex) in this deficit.

PMID- 16997510
TI  - Antimicrobial activity of cathelicidins BMAP28, SMAP28, SMAP29, and PMAP23
      against Pasteurella multocida is more broad-spectrum than host species specific.
AB  - The antimicrobial activity of linear, cationic alpha-helical peptides from cattle
      (BMAP28), sheep (SMAP28 and SMAP29), and pigs (PMAP23) were assessed to determine
      if activity was selective for Pasteurella multocida from a particular animal
      species or broad-spectrum against all P. multocida tested. The antimicrobial
      activities of synthetic peptides were determined for P. multocida isolated from
      cattle (10 isolates), sheep (10 isolates), and pigs (10 isolates) in a broth
      microdilution assay. All thirty isolates of P. multocida were susceptible to
      BMAP28 (MICs and MBCs, 1.0-1.9 microM); SMAP28 and SMAP29 (MICs and MBCs, 0.2-0.7
      microM); and PMAP23 (MICs and MBCs, 4.3 to > or = 6.8 microM). Overall, the
      results of this study suggest that synthesized cathelicidins from cattle, sheep,
      and pigs had broad-spectrum antimicrobial activity against all P. multocida.

PMID- 16997511
TI  - Immunoproteomic analysis of capsulate and non-capsulate strains of Lactococcus
      garvieae.
AB  - A comparative immunoproteomic study was carried out to investigate the
      immunogenicity of capsulate (KG9408) and non-capsulate (NSS9310) strains of
      Lactococcus garvieae. Immunoblot assays, following two-dimensional gel
      electrophoresis (2-DE) for L. garvieae strains, revealed a significant difference
      between anti-capsulate and anti-non-capsulate rabbit sera with respect to the
      number and antigenicity of antigenic spots. Anti-capsulate and anti-non-capsulate
      rabbit sera reacted with an average of 72 and 127 antigenic spots, respectively.
      The strong reaction of anti-non-capsulate sera with elongation factor (EF)-G and 
      Tu, and GMP synthase, of the L. garvieae strains identifies these as specific
      major antigens. This study clearly demonstrates the differences in 2-DE
      immunoblot profiles between the capsulate and non-capsulate strains of L.
      garvieae. These differences may be the reason for variations in immunogenicity
      between capsulate and non-capsulate strains. Glyceraldehyde-3-phosphate
      dehydrogenase, phosphoglycerate kinase, arginine deaminase and ornithine
      carbamoyltransferase were identified from the 2-DE immunoblot profiles of both
      strains. Therefore, these common antigens are potential markers for the
      development of vaccines against L. garvieae, irrespective of strain.
      Immunoproteomics, a powerful tool for studying antigens at the proteomic level,
      allowed a comparative investigation of the immunogenicity of capsulate and non
      capsulate strains of L. garvieae for vaccine development.

PMID- 16997512
TI  - Detection of hepatitis E virus in liver, mesenteric lymph node, serum, bile and
      faeces of naturally infected pigs affected by different pathological conditions.
AB  - The objective of the present study was to detect hepatitis E virus (HEV) in
      different samples from naturally infected pigs and to characterise genetically
      the detected strains. Serum, bile, liver, lymph nodes and faeces of 69 animals
      from 1 week to 4 months of age with different pathological conditions were
      collected. Reverse transcriptase-polymerase chain reaction (RT-PCR) to detect HEV
      and histopathology of tissues was conducted. Positive RT-PCR samples were
      sequenced and phylogenetically analysed. HEV was detected in at least one sample
      in 26 out of 69 animals (37.7%). Bile was the most frequently positive sample,
      followed by mesenteric lymph nodes, liver, faeces and serum. HEV was detected in
      pigs of 1 (n = 7), 2 (n = 8) and 3 (n = 11) months of age. A total of 22 of 69
      (31.9%) pigs had mild to moderate hepatitis and 15 of them were HEV RT-PCR
      positive in at least one of the tested samples. The highest sensitivity of viral
      detection was achieved using samples that cannot be obtained from live pigs, such
      as liver, mesenteric lymph node and bile. Phylogenetic analyses confirmed that
      all Spanish swine HEV strains detected belonged to genotype III. Therefore,
      genotype III strains are present in a relative high proportion of pigs between 1
      and 3 months of age. Through this study, it cannot be ruled out if concomitant
      infections may influence the distribution of HEV in infected pigs.

PMID- 16997513
TI  - Altered gene expression of transcriptional regulatory factors in tumor marker
      positive cells during chemically induced hepatocarcinogenesis.
AB  - Glutathione-S-transferase placental form (GST-P) is markedly and specifically
      inducible in rat chemical hepatocarcinogenesis and is a reliable marker protein
      for pre-neoplasia. To gain insights into the molecular mechanisms at the early
      stage of hepatocarcinogenesis and hepatotoxicity, we investigated the gene
      expression profile by DNA microarray analysis. We prepared RNA from GST-P
      positive foci in three individual rats and compared with normal liver sections
      from three individual rats, and labeled RNA was individually hybridized onto
      Affymetrix GeneChip Rat Expression Array 230A. DNA microarray analysis showed
      distinctly different profiles of dysregulated gene expression and supported the
      previous finding that some enzymes involved in metabolism and detoxification are
      overexpressed and suppressed. Here we discovered that several DNA-binding
      transcription factors and cofactors, including sterol-regulatory-element binding
      protein 1 (SREBP1) and Wilms' tumour 1 (WT1)-interacting protein, and their
      target genes were dysregulated in GST-P-positive foci. Moreover, genes involved
      in chromatin components, histone modification enzymes, and centrosome duplication
      were highly expressed. These genes were not previously known to be up-regulated
      during chemically induced hepatocarcinogenesis. DNA microarray analysis using RNA
      prepared from tumor marker-positive foci and control tissues provided a candidate
      gene link to the early stage of carcinogenesis and hepatotoxicity.

PMID- 16997514
TI  - The effects of soy extract on the uterus of castrated adult rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of different doses
      of a standardized soy extract on the uterus of castrated rats. METHODS: Fifty-six
      adult castrated female Wistar rats were randomly divided into seven groups (eight
      animals in each) that received: GI--drug vehicle (propylene glycol); GII--soy
      extract 10mg/kg per day; GIII--soy extract 50mg/kg per day; GIV--soy extract
      100mg/kg per day; GV--soy extract 300mg/kg per day; GVI--soy extract 600mg/kg per
      day; GVII-conjugated equine estrogens (CEE) 200microg/kg per day. After 21 days
      of treatment, all animals were sacrificed and fragments of the uterine horns were
      immediately removed, fixed in 10% formaldehyde and submitted to routine
      histological techniques for morphometric study. The endometrial cell
      proliferation index was determined with the PCNA antibody PC-10 and expressed as
      the percentuals of the PCNA-positive nuclei relative to the total countings.
      Other fragments were immediately frozen in liquid nitrogen for RNA extraction and
      VEGF analysis using RT-PCR technique. RESULTS: The minimal dose of soy extract
      that produced a significant increase of the morphometric parameters was 100mg/kg
      (GIV). The maximum effects on endometrial and myometrial morphometry were
      detected in the groups treated with 300 and 600mg/kg of soy extract (groups V and
      VI) and CEE (GVII). The expression of PCNA in the endometrial epithelium and
      stroma was increased by treatment with 100-600mg/kg per day of soy extract
      (groups IV-VI) or with CCE (group VII). Doses equal to or higher than 50mg/kg of
      soy extract (groups III-VI) and CEE stimulated the expression of VEGF.
      CONCLUSION: The treatment of adult castrated rats during 21 days with doses of
      100mg/kg per day or higher of soy extract may determine significant proliferation
      in the endometrium and myometrium.

PMID- 16997515
TI  - Pharmacokinetics of omeprazole after intravenous and oral administration to rats
      with liver cirrhosis induced by dimethylnitrosamine.
AB  - The aim of this study is to report the pharmacokinetics of omeprazole after
      intravenous (20 mg/kg) and oral (40 mg/kg) administration to rats with liver
      cirrhosis induced by dimethylnitrosamine (cirrhotic rats) with respect to CYP
      isozyme changes. The expressions of CYP1A2 and 3A1 decreased in cirrhotic rats
      and omeprazole is reported to be mainly metabolized via CYP1A1/2, 2D1, and 3A1/2
      in male Sprague-Dawley rats. Hence, the pharmacokinetics of omeprazole could be
      changed in cirrhotic rats. After intravenous administration to cirrhotic rats,
      the AUC (1180 microg min/ml versus 474 microg min/ml) and CL(NR) (17.4 ml/min/kg
      versus 42.3 ml/min/kg) of omeprazole were significantly greater and slower,
      respectively, than the controls. This could be due to decrease in the expressions
      of CYP1A2 and 3A1 in cirrhotic rats. The significantly slower CL(NR) could be
      supported by significantly slower in vitro CL(int) for the disappearance of
      omeprazole from hepatic microsomal study (0.102 ml/min/mg protein versus 0.144
      ml/min/mg protein) and slower hepatic blood flow rate in cirrhotic rats. After
      oral administration to cirrhotic rats, the AUC difference was considerably
      greater (451% versus 149%) than that after intravenous administration, possibly
      due to decrease in intestinal first-pass effect of omeprazole in addition to
      decrease in hepatic metabolism of omeprazole in cirrhotic rats.

PMID- 16997516
TI  - Multivariate toxicity screening of liposomal formulations on a human buccal cell
      line.
AB  - The influence of various formulation factors on the in vitro cellular toxicity of
      liposomes on human buccal cells (TR146), were studied by using the concept of
      statistical experimental design and multivariate evaluation. The factors
      investigated were the type of main phospholipid (egg-PC, DMPC, DPPC), lipid
      concentration, the type of charge, liposome size, and amount and nature of the
      charged component (diacyl-PA, diacyl-PG, diacyl-PS, stearylamine (SA), diacyl
      TAP) in the liposomes. Both full factorial design and D-optimal designs were
      created. Several significant main factors and interactions were revealed.
      Positively charged liposomes were shown to be toxic. The toxicity of negatively
      charged liposomes was relatively low. Diacyl-TAP was less toxic than SA, and DPPC
      was less toxic than DMPC. Low level of positively charged component was
      favourable and essential when using egg-PC as the main lipid. The amount of
      negatively charged component, the liposome size, and the total lipid
      concentration did not affect the toxicity within the experimental room. DPPC
      appeared to be a good candidate when formulating both positively and negatively
      charged liposomes with low cellular toxicity. The concept of statistical
      experimental design and multivariate evaluation was shown to be a useful approach
      in cell toxicity screening studies.

PMID- 16997517
TI  - In vitro study of polyoxyethylene alkyl ether niosomes for delivery of insulin.
AB  - In this study, niosomes of polyoxyethylene alkyl ethers (Brij) were prepared for
      encapsulation of insulin by film hydration method. Without cholesterol, brij 35
      and brij 58 did not form niosomes, apparently because of relatively large polar
      head groups in comparison with their alkyl chains. The size of vesicles depended
      on the cholesterol content, charge incorporation or hydrophilicity of
      surfactants. Entrapment of insulin in bilayer structure of niosomes protected it
      against proteolytic activity of alpha-chymotrypsin, trypsin and pepsin in vitro.
      The maximum protection activity was seen in brij 92/cholesterol (7:3 molar
      ratios) in which only 26.3+/-3.98% of entrapped insulin was released during 24h
      in simulated intestinal fluid (SIF). The kinetic of drug release for most
      formulations could be best described by Baker and Lonsdale equation indicating
      diffusion based delivery mechanism. These results indicate that niosomes could be
      developed as sustained release oral dosage forms for delivery of peptides and
      proteins such as insulin.

PMID- 16997518
TI  - Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein
      mediated drug resistant tumor cells.
AB  - The over-expression of P-glycoprotein (P-gp) has been associated with the
      development of multidrug resistance (MDR) in cancer cells. In this study, we
      examined whether transferrin receptor (Tf-R) targeted liposomes can efficiently
      deliver encapsulated doxorubicin (DXR) into MDR cells (SBC-3/ADM) via Tf-R
      mediated endocytosis thus overcoming MDR by by-passing P-gp-mediated drug efflux.
      We prepared four types of liposome, i.e. untargeted and Tf-R-targeted, made of
      either egg-PC/cholesterol or hydrogenated egg PC/cholesterol. Only with the
      targeted EPC-liposome we achieved significant delivery of encapsulated DXR and
      increased cytotoxicity of encapsulated DXR on the MDR cells (3.5-fold higher than
      free DXR). Confocal microscopy and an intracellular drug-accumulation assay
      indicated that the targeted liposomes efficiently delivered DXR into cells where
      it readily accumulated in the nucleus, in both drug-sensitive and MDR cells.
      These findings suggest that the targeted liposomes are rapidly internalized via
      Tf-R-mediated endocytosis followed by release of their contents into the
      cytoplasm. The rapid internalization and content release, most likely facilitated
      by the higher fluidity of the EPC-based liposomes, may explain why only targeted
      EPC-liposomes were able to prevent drug efflux by P-gp and to consequently
      circumvent MDR. Our results indicate that in order to achieve MDR circumvention
      by means of liposomal encapsulation of DXR the liposomes not only need to be
      targeted, but also to have the proper physicochemical properties for adequate
      release of the drug. Furthermore, these in vitro results suggest that Tf-R
      targeted EPC-liposomes are a potentially useful drug delivery system to
      circumvent P-gp-mediated MDR of tumors.

PMID- 16997519
TI  - Mannosylated liposomes for bio-film targeting.
AB  - Vesicular systems in general are investigated to achieve bacterial bio-film
      targeting as their architecture mimics bio-membranes in terms of structure and
      bio-behavior. This paper elaborates upon the role of the inherent characteristics
      of the carrier system and further envisages the role of anchored ligands in
      navigating the contents in the vicinity of bio-films. Vesicles in the present
      study were coated with hydrophobic derivatives of mannan (cholesteryl mannan and
      sialo-mannan). The prepared vesicles were characterized for size, shape,
      percentage entrapment and ligand binding specificity and results were compared
      with the uncoated versions. Using a set of in vitro and in vivo models, the bio
      film targeting potential of plain and mannosylated liposomal formulations were
      compared. Results suggested that mannosylated vesicles could be effectively
      targeted to the model bacterial bio-films, compared with plain vesicles.
      Moreover, the sialo-mannan coated liposomes recorded superior targetability as
      reflected in the significantly higher percentage growth inhibition when compared
      with cholesteryl mannan coated liposomes. The engineered systems thus have the
      potential use for the delivery of anti-microbial agents to the bio-films.

PMID- 16997520
TI  - Enhancing effect of surfactants on fexofenadine.HCl transport across the human
      nasal epithelial cell monolayer.
AB  - The effect of various surfactants (sodium cholate, sodium taurocholate, Tween 80
      and Poloxamer F68) on enhancing the transepithelial permeability of
      fexofenadine.HCl was evaluated in a human nasal epithelial cell monolayer model.
      The cytotoxicity of the surfactants on the human nasal epithelial cells was
      evaluated by the MTT assay. A dose-dependent reduction of cell viability was
      observed at higher than critical micelle concentration (CMC) of the surfactants,
      and the IC50 of non-ionic surfactants (Tween 80 and Poloxamer F68) was higher
      than that of ionic surfactants (sodium cholate and sodium taurocholate). The TEER
      values significantly decreased after 2 h incubation with the ionic surfactants,
      but were recovered after 24 h in the fresh culture media. Ionic surfactants
      significantly increased the transepithelial permeability (P(app)) of
      fexofenadine.HCl compared to the non-ionic surfactants. The reduction of TEER
      values upon exposing the cell monolayer to the surfactants for 2 h correlated
      well with the P(app) of fexofenadine.HCl, which suggests that the permeation
      enhancing mechanism of the ionic surfactants is by altering the tight junction
      property of the paracellular pathway. F-actin staining showed that the effect of
      ionic surfactants on the tight junction is temporary and reversible, which is
      consistent with the TEER value recovery within 24 h. These results imply that
      ionic surfactants are potentially useful permeation enhancers for nasal delivery
      of hydrophilic compounds, such as fexofenadine.HCl. This study also indicated the
      usefulness of the human nasal epithelial cell monolayer model not only for
      evaluating the in vitro nasal drug transport but also for studying the mechanism
      and toxicity of enhancers.

PMID- 16997521
TI  - Assessment of antidiarrhoeal activity of the methanol extract of Xylocarpus
      granatum bark in mice model.
AB  - The methanol extract of Xylocarpus granatum bark was studied for its
      antidiarrhoeal properties in experimental diarrhoea, induced by castor oil and
      magnesium sulphate in mice. At the doses of 250 and 500 mg/kg per oral, the
      methanol extract showed significant and dose-dependent antidiarrhoeal activity in
      both models. The extracts also significantly reduced the intestinal transit in
      charcoal meal test when compared to atropine sulphate (5 mg/kg; i.m.). The
      results showed that the extracts of Xylocarpus granatum bark have a significant
      antidiarrhoeal activity and supports its traditional uses in herbal medicine.

PMID- 16997522
TI  - Use of multislice computed tomography in disaster victim identification-
      advantages and limitations.
AB  - After a mass fatality incident (MFI), all victims have to be rapidly and
      accurately identified for juridical reasons as well as for the relatives' sake.
      Since MFIs are often international in scope, Interpol has proposed standard
      disaster victim identification (DVI) procedures, which have been widely adopted
      by authorities and forensic experts. This study investigates how postmortem
      multislice computed tomography (MSCT) can contribute to the DVI process as
      proposed by Interpol. The Interpol postmortem (PM) form has been analyzed, and a
      number of items in sections D and E thereof have been postulated to be suitable
      for documentation by CT data. CT scans have then been performed on forensic
      cases. Interpretation of the reconstructed images showed that indeed much of the
      postmortem information required for identification can be gathered from CT data.
      Further advantages of the proposed approach concern the observer independent
      documentation, the possibility to reconstruct a variety of images a long time
      after the event, the possibility to distribute the work by transmitting CT data
      digitally, and the reduction of time and specialists needed at the disaster site.
      We conclude that MSCT may be used as a valuable screening tool in DVI in the
      future.

PMID- 16997523
TI  - Application of 3D documentation and geometric reconstruction methods in traffic
      accident analysis: with high resolution surface scanning, radiological MSCT/MRI
      scanning and real data based animation.
AB  - The examination of traffic accidents is daily routine in forensic medicine. An
      important question in the analysis of the victims of traffic accidents, for
      example in collisions between motor vehicles and pedestrians or cyclists, is the
      situation of the impact. Apart from forensic medical examinations (external
      examination and autopsy), three-dimensional technologies and methods are gaining
      importance in forensic investigations. Besides the post-mortem multi-slice
      computed tomography (MSCT) and magnetic resonance imaging (MRI) for the
      documentation and analysis of internal findings, highly precise 3D surface
      scanning is employed for the documentation of the external body findings and of
      injury-inflicting instruments. The correlation of injuries of the body to the
      injury-inflicting object and the accident mechanism are of great importance. The
      applied methods include documentation of the external and internal body and the
      involved vehicles and inflicting tools as well as the analysis of the acquired
      data. The body surface and the accident vehicles with their damages were
      digitized by 3D surface scanning. For the internal findings of the body, post
      mortem MSCT and MRI were used. The analysis included the processing of the
      obtained data to 3D models, determination of the driving direction of the
      vehicle, correlation of injuries to the vehicle damages, geometric determination
      of the impact situation and evaluation of further findings of the accident. In
      the following article, the benefits of the 3D documentation and computer
      assisted, drawn-to-scale 3D comparisons of the relevant injuries with the damages
      to the vehicle in the analysis of the course of accidents, especially with regard
      to the impact situation, are shown on two examined cases.

PMID- 16997525
TI  - Pesticide poisoning in domestic animals and livestock in Austria: a 6 years
      retrospective study.
AB  - A 6 years retrospective study of pesticide poisonings in domestic animals and
      livestock from 1999 to 2004 submitted to the Institute for Medical Chemistry,
      University of Veterinary Medicine, Vienna in Austria was compiled and analysed.
      Totally 380 pesticide analysis requests were referred by veterinary
      practitioners, from the Institute for Pathology of the above university, by
      regional and central governments as well as local police departments and district
      administrations, animal protectionist groups, public health authorities and
      private clients. Among the total number of suspected samples for pesticides, 175
      (46.1%) cases were found positive to contain pesticides of various kinds. Among
      the pesticides found, carbamate insecticides were most prominent, representing
      50.3% of the total positive cases. These compounds were followed by rodenticides
      anticoagulants with 18.9% of the positive results, by organophosphate
      insecticides 5.1%, and by the rodenticides-nonanticoagulant 3.4%, the other 22.3%
      included molluscicides, herbicides, etc. In totally 225 animals, 123 animals were
      found positive for pesticide intoxication, among them 47.2% were dogs, 34.1% were
      cats 9.8% of other species and 8.9% of unspecified animal samples. The pesticides
      were characterized by HPLC-techniques using commercially available standards. The
      aim of this Austrian survey was to determine the incidence and frequency of
      confirmed pesticide intoxications in animals in Austria and to emphasize its
      relevance in veterinary practice for livestock and domestic animals.

PMID- 16997526
TI  - Neonatal gastrointestinal imaging.
AB  - Radiological imaging is an important part of the evaluation and management of
      neonates with suspected anomalies of the gastrointestinal tract. Clinical
      presentation is often non-specific, commonly with abdominal distension and
      vomiting for which the underlying cause may or may not be clinically apparent. In
      a proportion of patients, the clinical assessment alone may suffice in providing
      the diagnosis and no further imaging is necessary. The reader must have an
      understanding of the normal radiographic appearances of the gastrointestinal
      tract in neonates and appreciate normal variants and differences to adults. In
      certain cases, the abdominal radiograph alone is diagnostic. In others,
      sonography and contrast studies are useful adjunct investigations and the
      indications for CT and MRI are few, but specific. Appropriate radiological
      investigation will help to establish the diagnosis and guide surgical
      intervention whilst also avoiding unnecessary radiation. Some of the conditions
      require transfer to specialist paediatric institutions for care. Thus, in some
      circumstances it is appropriate for imaging to be delayed and performed at the
      specialist centre with early referral often essential for the continued well
      being of the child.

PMID- 16997527
TI  - Protein secretion pathways in Bacillus subtilis: implication for optimization of
      heterologous protein secretion.
AB  - The absence of an outer membrane in Bacillus subtilis can simplify the protein
      secretion pathways and allow the organism to secrete high levels of extracellular
      proteins. Of the three known secretory routes, Sec-SRP pathway can direct the
      majority of secretory proteins into the growth medium. Alternatively, a small
      number of exoproteins with specific functions are secreted via Tat pathway or ABC
      transporters in B. subtilis. The discriminating function of precursor proteins
      among these pathways is largely attributed to the distinct structure of their
      cleavable signal peptides. Individual secretion machinery components with their
      special functions are involved in the total flow of proteins from the cytoplasm
      to the medium. Notably, multiple regulators with signal transduction functions
      can affect expression of secretion machinery as well as their post
      transcriptional actions for protein secretion, resulting in the complicated
      networks in B. subtilis. Ultimately, according to the available knowledge of
      secretion machinery, several approaches aimed at optimizing protein secretion are
      discussed.

PMID- 16997528
TI  - Tex, a putative transcriptional accessory factor, is involved in pathogen fitness
      in Streptococcus pneumoniae.
AB  - We have identified a pneumococcal gene, tex, which has the potential to regulate
      gene expression. The tex gene is named for its role in toxin expression in
      Bordetella pertussis, where it was characterized as an essential gene. Homologous
      sequences have been found in both Gram-positive and Gram-negative bacteria and
      are highly conserved at the protein level. Tex family proteins contain a S1 RNA
      binding domain at the C-terminus. Members of this family are putative
      transcriptional accessory factors. Although tex in Streptococcus pneumoniae is
      homologous to that in B. pertussis, there are distinct differences. Since the tex
      gene in S. pneumoniae is not an essential gene, we were able to delete tex in
      strain D39. The tex knockout mutant, DeltaTex, did not affect production of the
      pneumococcal toxin pneumolysin. However, we observed decreased growth of DeltaTex
      in the presence of the wild-type strain both in vitro and in vivo as determined
      by generation numbers and competitive index (CI). The interaction between
      recombinant Tex and nucleic acids was confirmed by southwestern and northwestern
      analysis, supporting its role as a transcriptional accessory factor.

PMID- 16997529
TI  - Hair pulling and its affective correlates in an African-American university
      sample.
AB  - Like other clinical phenomena, repetitive hair pulling in African-Americans has
      attracted little systematic investigation. Slightly over 200 participants were
      recruited from a historically black university. Participants completed the Hair
      Pulling Scale [Stanley, M. A., Borden, J. W., Bell, G. E., & Wagner, A. L.
      (1994). Nonclinical hair pulling: phenomenology and related psychopathology.
      Journal of Anxiety Disorders, 8, 119-130], the Beck Depression Inventory, and the
      Beck Anxiety Inventory (BAI). Ten percent of the African-American sample thought
      about pulling out hair and 6.3% actually pulled out hair. A variety of types of
      affect was reported before, during, and after pulling or picking. Several
      statistically significant relationships were found: status as a person who thinks
      about pulling out hair is significantly correlated with anxiety as measured by
      the BAI (r=.265, p=.000), status as a person who pulls hair is significantly
      correlated with anxiety as measured by the BAI (p=.192, r=.007). Implications are
      discussed.

PMID- 16997531
TI  - Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive
      model updated and revisited.
AB  - Recent investigation suggests a strong relationship between immunological effects
      and the pathophysiology of schizophrenia. Two prevalent approaches exist to this
      association. First, is more empirical a-priori research investigating
      immunological changes prevalent in schizophrenia and the second approach is more
      hypothesis-driven with analysis of immunological changes in schizophrenia based
      on known irregularities of the illness. The former approach is based upon three
      predominant lines of investigation including observations of a diffuse non
      specific overactivation of the immunological response system, of a T-helper cell
      type 1 immune activation and of a T-helper cell type 2 immune activation in
      subgroups of schizophrenia patients. These last two theories suggest that a
      subgroup of patients with schizophrenia may demonstrate features of an autoimmune
      process, a theory supported by a growing database of investigation. The latter
      approach notes that many observations of immune dysregulation in schizophrenia
      overlap with central etiopathophysiological mechanisms as well as with clinical
      manifestations of the illness. Immunotherapy offers the opportunity to modify or
      re-balance the immune system and may become useful in management of the illness.
      Given that autoimmune mechanisms could interrupt neurotransmission, any process
      interfering with this disruption including therapeutic antibodies to involved
      cytokines, or with various other natural autoantibodies or immune system
      regulators, may become useful in the augmentative management of the illness.

PMID- 16997530
TI  - A 1.5-Mb-resolution radiation hybrid map of the cat genome and comparative
      analysis with the canine and human genomes.
AB  - We report the construction of a 1.5-Mb-resolution radiation hybrid map of the
      domestic cat genome. This new map includes novel microsatellite loci and markers
      derived from the 2X genome sequence that target previous gaps in the feline-human
      comparative map. Ninety-six percent of the 1793 cat markers we mapped have
      identifiable orthologues in the canine and human genome sequences. The updated
      autosomal and X-chromosome comparative maps identify 152 cat-human and 134 cat
      dog homologous synteny blocks. Comparative analysis shows the marked change in
      chromosomal evolution in the canid lineage relative to the felid lineage since
      divergence from their carnivoran ancestor. The canid lineage has a 30-fold
      difference in the number of interchromosomal rearrangements relative to felids,
      while the felid lineage has primarily undergone intrachromosomal rearrangements.
      We have also refined the pseudoautosomal region and boundary in the cat and show
      that it is markedly longer than those of human or mouse. This improved RH
      comparative map provides a useful tool to facilitate positional cloning studies
      in the feline model.

PMID- 16997532
TI  - Anticonvulsant activity, neural tube defect induction, mutagenicity and
      pharmacokinetics of a new potent antiepileptic drug, N-methoxy-2,2,3,3
      tetramethylcyclopropane carboxamide.
AB  - N-methoxy-2,2,3,3-tetramethylcyclopropane carboxamide (OM-TMCD) is a methoxyamide
      derivative of a cyclopropyl analogue of valproic acid (VPA). The structural
      considerations used in the design of OM-TMCD were aimed to enhance OM-TMCD
      anticonvulsant potency (compared to VPA) and to prevent VPA's two life
      threatening side effects, i.e., induction of neural tube defects (NTDs) and
      hepatotoxicity. Following i.p. administration to rats OM-TMCD demonstrated a
      broad spectrum of anticonvulsant activity and showed better potency than VPA in
      the maximal electroshock seizure and subcutaneous pentylenetetrazole tests as
      well as in the hippocampal kindling model. OM-TMCD was inactive in the mouse 6-Hz
      test at 100 mg/kg dose. Teratogenicity studies performed in a SWV/Fnn-mouse model
      for VPA-induced-exencephaly showed that on the equimolar basis OM-TMCD possesses
      the same fetal toxicity and ability to induce NTDs as VPA, but since OM-TMCD is a
      much more potent anticonvulsant its activity/exencephaly formation ratio appears
      to be much more beneficial than that of VPA. OM-TMCD was found to be non
      mutagenic and non-pro-mutagenic in the Ames test. It showed a beneficial
      pharmacokinetic profile in rats, having a high oral bioavailability of 75% and
      satisfactory values of clearance and volume of distribution. These results
      support further studies to fully characterize the therapeutic potential of OM
      TMCD.

PMID- 16997533
TI  - Reversal of androgenetic alopecia by topical ketoconzole: relevance of anti
      androgenic activity.

PMID- 16997534
TI  - Membrane fatty acids, reading and spelling in dyslexic and non-dyslexic adults.
AB  - Increasing evidence implicates functional deficiencies or imbalances of omega-3
      and omega-6 fatty acids in dyslexia. The associations between literacy skills and
      omega-3 and omega-6 fatty acid status were examined. 32 dyslexics and 20 controls
      completed standardised tests of reading and spelling and gave venous blood
      samples for analysis of the polar lipid fatty acid composition of red blood cell
      (RBC) membranes. Relationships between literacy skills and omega-3 and omega-6
      concentrations were examined using rank-order correlations. Better word reading
      was associated with higher total omega-3 concentrations in both dyslexic and
      control groups. In dyslexic subjects only, reading performance was negatively
      associated with the ratio of arachidonic acid/eicosapentaenoic acid (ARA/EPA) and
      with total omega-6 concentrations. There were no significant differences in
      membrane fatty acid levels between the dyslexic and control subjects. However,
      the finding that omega-3 status was directly related to reading performance
      irrespective of dyslexia supports a dimensional view of this condition, and our
      results also suggest that it is the omega-3/omega-6 balance that is particularly
      relevant to dyslexia.

PMID- 16997536
TI  - Extinction coefficient of gold nanoparticles with different sizes and different
      capping ligands.
AB  - Extinction coefficients of gold nanoparticles with core size ranging from
      approximately 4 to 40 nm were determined by high resolution transmission electron
      microscopy analysis and UV-vis absorption spectroscopic measurement. Three
      different types of gold nanoparticles were prepared and studied: citrate
      stabilized nanoparticles in five different sizes; oleylamide-protected gold
      nanoparticles with a core diameter of 8 nm, and a decanethiol-protected
      nanoparticle with a diameter of around 4 nm. A linear relationship between the
      logarithms of extinction coefficients and core diameters of gold particles was
      found independent of the capping ligands on the particle surface and the solvents
      used to dissolve the nanoparticles. This linear relation may be used as a
      calibration curve to determine the concentration or average size of an unknown
      nanoparticle or nanoparticle-biomolecule conjugate sample.

PMID- 16997535
TI  - The role of noradrenergic tone in the dorsal raphe nucleus of the mouse in the
      acute behavioral effects of antidepressant drugs.
AB  - Serotonin neurons of the dorsal raphe nucleus (DRN) receive dense noradrenergic
      innervation and are under tonic activation by noradrenergic input. Thus, afferent
      noradrenergic input to the DRN could modify the antidepressant effects of
      selective serotonin reuptake inhibitors (SSRIs) by regulating serotonergic
      transmission. This study investigated whether noradrenergic innervation of the
      DRN contributes to the acute behavioral effects of different types of
      antidepressant drugs in the mouse tail suspension test (TST). Noradrenergic
      terminals in the DRN were destroyed selectively by the local application of 6
      hydroxydopamine (6-OHDA). Immunohistochemical analysis confirmed the presence of
      noradrenergic fibers in the mouse DRN, that 6-OHDA-induced destruction of
      noradrenergic terminals was confined to the DRN, and serotonergic cell bodies
      were not affected by 6-OHDA treatment. The antidepressants tested included the
      SSRIs, fluoxetine and citalopram, and the norepinephrine reuptake inhibitor (NRI)
      desipramine. The behavioral effects of fluoxetine (20 mg/kg, IP) were blocked by
      the destruction of noradrenergic terminals. In contrast, pretreatment with 6-OHDA
      did not alter the ability of citalopram (20 mg/kg, IP) or desipramine (10 mg/kg,
      IP) to reduce immobility in the TST. Destruction of noradrenergic projections
      from the locus ceruleus (LC) by DSP-4 treatment did not alter the behavioral
      effects of any of the antidepressants tested, or the presence of noradrenergic
      terminals in the DRN, thus indicating that noradrenergic pathways originating
      from the LC do not mediate the acute behavioral effects of antidepressants in
      this test. Thus, afferent noradrenergic activity at the level of the DRN can
      modulate serotonergic transmission in forebrain structures and the behavioral
      effects of SSRIs, such as fluoxetine, which use noradrenergic input to the DRN to
      increase forebrain serotonin.

PMID- 16997538
TI  - High intake of alcohol is associated with newly diagnosed diabetes in 60 years
      old men and women.
AB  - BACKGROUND AND AIMS: Low or moderate alcohol intake has been found to be
      protective against the incidence of diabetes, while conflicting results have been
      found regarding high alcohol intake. This study aimed at evaluating the effect of
      alcohol intake on newly diagnosed diabetes among subjects aged 60 years in
      relation to anthropometric measurements, life-style and socio-economic factors.
      METHODS AND RESULTS: A population-based cross-sectional study of 4106
      individuals, 1973 men and 2133 women, aged 60 years, in Stockholm County, Sweden.
      Medical history, socio-economic factors and life-style data were collected by a
      questionnaire and a medical examination including laboratory tests. High total
      intake of alcohol, i.e. >30 g/day vs. 0-30 g/day, was significantly noted more
      often in newly diagnosed diabetes in men (OR 2.72, 95% CI 1.70-4.34), even when
      adjusting for other factors, i.e. anthropometric measurements, life-style, socio
      economic and dietary factors (adjusted OR 1.94, 95% CI 1.17-3.23); a high intake
      of spirits, i.e. >15 g/day vs. 0-15 g/day, was significantly more often observed
      among women (OR 3.97, 95% CI 1.50-10.50), however, it was not significant after
      adjustment (OR 2.23, 95% CI 0.67-7.42). CONCLUSION: High intake of alcohol among
      men was associated with increased risk of diabetes even when adjusting for other
      factors.

PMID- 16997537
TI  - Prodrugs of scutellarin: ethyl, benzyl and N,N-diethylglycolamide ester
      synthesis, physicochemical properties, intestinal metabolism and oral
      bioavailability in the rats.
AB  - In an effort to enhance the oral bioavailability of scutellarin, ethyl, benzyl
      and N,N-diethylglycolamide ester of scutellarin were synthesized. The hydrolysis
      of the prodrugs follows first-order kinetics in aqueous solution, and produced a
      V-shaped pH profile. The N,N-diethylglycolamide ester is highly susceptible to
      enzymatic hydrolysis in human plasma (t(1/2) approximately 7 min) with a high
      stability in aqueous solution (t(1/2) approximately 16 day, pH 4.2). Compared
      with the solubility of scutellarin, the solubility of glycolamide ester was about
      ten times in pH 4.0 buffer, and about thirty five times in water. Its apparent
      partition coefficient increased significantly from -2.56 to 1.48. Glycolamide
      ester of scutellarin was chosen to investigate the intestinal metabolism and in
      vivo bioavailability. Degradation studies in the intestinal tract content and
      homogenates indicated intestinal metabolism before absorption was a crucial
      obstacle for the prodrug. N,N-Diethylglycolamide ester can be protected from the
      degradation in the intestinal lumen by an emulsion. A significant increase in the
      plasma AUC and C(max) of the prodrug emulsion was observed in rats, compared with
      that of the scutellarin-cyclodextrin complex (P<0.01). The emulsion of N,N
      diethylglycolamide ester produces a 1.58-fold enhancement in apparent
      bioavailability and 1.4-fold increase in the absolute bioavailability compared to
      the scutallarin-cyclodextrin complex.

PMID- 16997539
TI  - Phenolic-rich juice prevents DNA single-strand breakage and cytotoxicity caused
      by tert-butylhydroperoxide in U937 cells: the role of iron chelation.
AB  - The antioxidant potential of phenolic compounds is generally linked to their
      ability to scavenge free radicals. However, in addition to their radical
      scavenging activity, phenolic compounds can chelate metal ions, such as iron, to
      prevent their participation in Fenton-type reactions, which lead to the formation
      of free radicals. The aim of the present study was to evaluate the ability of a
      phenolic-rich juice made from grapes, cherries and berries to protect human
      myeloid leukemia (U937) cells from oxidative stress caused by tert
      butylhydroperoxide (tB-OOH). Preincubation of cells with extracts of the phenolic
      rich juice at different concentrations (0-200 microM ferulic acid equivalents)
      for 3 h partially prevented cell death and abolished the DNA cleavage induced by
      tB-OOH. Moreover, when preincubating cells with the 100-microM juice extract (the
      dose that diminished cell death by around 50%), the partial prevention of tB-OOH
      induced formation of reactive oxygen species (ROS) and mitochondrial permeability
      transition pore opening was observed. The radical scavenger antioxidant N,N'
      diphenyl-1,4-phenylene-diamine (DPPD) and the intracellular iron chelator o
      phenanthroline (o-Phe) were also tested to know whether protective effects
      depended on radical-scavenging or iron-chelating activities. o-Phe prevented cell
      death, DNA cleavage and ROS generation, whereas DPPD only prevented cell death,
      suggesting that phenolics in the juice afforded protection against induced
      oxidative stress, most probably by means of an iron-chelating mechanism.

PMID- 16997540
TI  - Cardiac nitric oxide synthases are elevated in dietary copper deficiency.
AB  - Dietary copper (Cu) deficiency leads to cardiac morphological and functional
      defects suggestive of heart failure. However, simultaneous cytoprotective events
      also appear to occur. The molecular mechanisms responsible for this complex
      alteration of cardiac function by Cu deficiency have not been elucidated. Because
      prior work has implicated altered nitric oxide (NO) metabolism in this altered
      function, we have examined this pathway in further detail. Male Sprague-Dawley
      rats were fed diets that were either Cu adequate (6 mg Cu/kg diet) or Cu
      deficient (<0.5 mg Cu/kg diet) for 5 weeks. Endothelial NO synthase (NOS) and
      inducible NOS (iNOS) protein expressions, as measured by Western blot analysis,
      were 58% and 40% higher, respectively, in Cu-deficient than in Cu-adequate rat
      hearts. Cardiac NOS activity, as measured by conversion of (3)H-arginine to (3)H
      citrulline, was 130% higher in Cu-deficient than in Cu-adequate rats. NFkappaB is
      a known transcription factor for iNOS. Activation of NFkappaB, determined by an
      ELISA for the p65 subunit, was found to be 33% higher in Cu-deficient than in Cu
      adequate rats. Coupled with prior evidence of elevated cardiac nitrate/nitrite
      production in Cu-deficient rats, these data suggest multiple pathways for
      enhanced NO production that may contribute to altered cardiac function under
      dietary Cu deficiency.

PMID- 16997541
TI  - Conjugated linoleic acid protects against age-associated bone loss in C57BL/6
      female mice.
AB  - Osteoporosis is one of the major causes of morbidity in the elderly. Inflammation
      exerts a significant influence on bone turnover, inducing the chronic form of
      osteoporosis. Dietary nutrition has the capacity to modulate inflammatory
      response. Therefore, nutritional strategies and lifestyle changes may prevent age
      related osteoporosis, thereby improving the quality of life of the elderly
      population. Conjugated linoleic acid (CLA) has been shown to positively influence
      calcium and bone metabolism. Hence, this study was undertaken to examine the
      effect of CLA on bone mineral density (BMD) in middle-aged C57BL/6 female mice.
      After 10 weeks on diet, CLA-fed mice (14 months) maintained a higher BMD in
      different bone regions than corn oil (CO)-fed mice. The increased BMD was
      accompanied by a decreased activity of proinflammatory cytokines (such as tumor
      necrosis factor alpha, interleukin-6 and the receptor activator of NF-kappaB
      ligand) and decreased osteoclast function. Furthermore, a significant decrease in
      fat mass and an increase in muscle mass were also observed in CLA-fed mice
      compared to CO-fed mice. In conclusion, these findings suggest that CLA may
      prevent the loss of bone and muscle mass by modulating markers of inflammation
      and osteoclastogenic factors.

PMID- 16997542
TI  - Utilization of waste glass in ECO-cement: strength properties and microstructural
      observations.
AB  - Waste glass creates a serious environmental problem, mainly because of the
      inconsistency of the waste glass streams. The use of waste glass as a finely
      ground mineral additive (FGMA) in cement is a promising direction for recycling.
      Based on the method of mechano-chemical activation, a new group of ECO-cements
      was developed. In ECO-cement, relatively large amounts (up to 70%) of portland
      cement clinker can be replaced with waste glass. This report examines the effect
      of waste glass on the microstructure and strength of ECO-cement based materials.
      Scanning electron microscopy (SEM) investigations were used to observe the
      changes in the cement hydrates and interface between the cement matrix and waste
      glass particles. According to the research results, the developed ECO-cement with
      50% of waste glass possessed compressive strength properties at a level similar
      to normal portland cement.

PMID- 16997543
TI  - Long-term leaching test of incinerator bottom ash: evaluation of Cu partition.
AB  - Two types of leaching tests were performed on the bottom ash from municipal solid
      waste incinerators. A short-term batch test specified by the America Nuclear
      Society (ANS) and long-term column tests with acetic acid (pH 5.2) as leaching
      solution were used to evaluate copper leachability. The Cu leaching after the 5-d
      ANS test is about 1% of the original Cu content of 5300 mg/kg. Upon addition of a
      stabilizing agent, the Cu leaching quantity is reduced; the extent of reduction
      depends on the type of chemical used (phosphate, carbonate and sulfide). The 1.6%
      Na(2)S addition showed negligible Cu leaching, and Na(2)S was, therefore, used in
      subsequent column tests. The 30-d column test indicates a steady increase of Cu
      leaching amount with time and reaches about 1.5% of the original Cu content after
      30 d. A 180-d column test further increased the Cu leaching to about 5.1% of the
      original Cu content, whereas no appreciable Cu leaching was found with the
      addition of 1.6% Na(2)S. A sequential extraction was conducted on the raw ash,
      ash with the addition of Na(2)S and the residue ash after 30 d of operation to
      characterize Cu affinity for different solid fractions. The data were used to
      evaluate the fate of Cu through these interactions.

PMID- 16997544
TI  - Three dimensional electrode array for cell lysis via electroporation.
AB  - Microfabricated devices for cell lysis have demonstrated many advantages over
      conventional approaches. Among various design of microdevices that employ
      electroporation for cytolysis, most utilize Ag/AgCl wires or 2D planar
      electrodes. Although, simple in fabrication the electric field generated by 2D
      electrodes decays exponentially, resulting in rather non-uniform forcing on the
      cell membrane. This paper investigates the effect of electric field generated by
      3D cylindrical electrodes to perform cell lysis via electroporation in a
      microfluidic platform, and compared with that by 2D design. Computational results
      of the electric field for both 2D and 3D electrode geometries showed that the 3D
      configuration demonstrated a significantly higher effective volume ratio-volume
      which electric field is sufficient for cell lysis to that of net throughflow
      volume. Hence, the efficacy of performing cell lysis is substantially greater for
      cells passing through 3D than 2D electrodes. Experimentally, simultaneous multi
      pores were observed on leukocytes lysed with 3D electrodes, which is indicative
      of enhanced uniformity of the electric field generated by 3D design.
      Additionally, a single row of 3D electrode demonstrated a substantially higher
      lysing percentage (30%) than that of 2D (8%) under that same flow condition. This
      work should aid in the design of electrodes in performing cell lysis via
      electroporation.

PMID- 16997545
TI  - The use of Eucalyptus tereticornis Sm. (Myrtaceae) oil (leaf extract) as a
      natural larvicidal agent against the malaria vector Anopheles stephensi Liston
      (Diptera: Culicidae).
AB  - Secondary metabolites obtained from the indigenous plants with proven mosquito
      control potential can be used as an alternative to synthetic insecticides under
      the integrated vector control. The essential oil extract from the forest redgum,
      Eucalyptus tereticornis Sm. (Myrtaceae) was tested against mature and immature
      mosquito vector Anopheles stephensi Liston (Diptera) under laboratory condition.
      The extract showed strong larvicidal, pupicidal and adulticidal activity. The
      leaf oil extracts showed high bioactivity at high doses. Results obtained from
      the laboratory experiment showed that the leaf extracts suppressed the pupal and
      adult activity of Anopheles stephensi at higher doses. In general, first and
      second instar larvae were more susceptible to all treatments. Clear dose 
      response relationships were established with the highest dose of 160ppm plant
      extract evoking almost 100% mortality. The results obtained suggest that, in
      addition to their medicinal activities, E. tereticornis can also serve as a
      natural mosquitocide.

PMID- 16997546
TI  - The catalytic mode of cysteine proteinases of papain (C1) family.
AB  - The Proton Inventory (PI) method has been applied in the hydrolysis of synthetic
      substrates by papain, chymopapain and stem bromelain, comparing also their
      corresponding pH-(k(cat)/K(m)) profiles, and it was found: (a) k(cat)/K(m)=k(1),
      and thus K(S)=k(2)/k(1) is a dynamic equilibrium constant, (b) bowed-downward PI
      for k(cat)/K(m) exhibiting large inverse SIE, and (c) linear PI exhibiting large
      normal SIE for K(S), k(2) and k(3). A novel finding of this work is that the
      association of substrates onto all three studied cysteine proteinases proceeds
      via a stepwise pathway, in contrast to purely concerted pathways found previously
      for both acylation and deacylation. A hydrogen bond, which seems more likely to
      be developed across a pK(a)-value close to 4.00, connecting [see text]
      (papain/chymopapain or bromelain numbering), constitutes another novelty of this
      work.

PMID- 16997547
TI  - Biosorption of anionic textile dyes by nonviable biomass of fungi and yeast.
AB  - The nonviable biomass of Aspergillus niger, Aspergillus japonica, Rhizopus
      nigricans, Rhizopus arrhizus, and Saccharomyces cerevisiae were screened for
      biosorption of textile dyes. The selected anionic reactive dyes were C.I.
      Reactive Black 8, C.I. Reactive Brown 9, C.I. Reactive Green 19, C.I. Reactive
      Blue 38, and C.I. Reactive Blue 3. Experiments were conducted at initial dye
      concentration of 50, 100, 150 and 200mg/L. The effect of initial dye
      concentration, dose of biosorbent loading, temperature, and pH on adsorption
      kinetics was studied. S. cerevisiae and R. nigricans were good biosorbents at
      initial dye concentration of 50mg/L, 1g% (w/v) biomass loading and 29+/-1 degrees
      C. R. nigricans adsorbed 90-96% dye in 15min, at 20 degrees C and pH 6.0. The
      data showed an optimal fit to the Langmuir and Freundlich isotherms. The maximum
      uptake capacity (Q(o)) for the selected dyes was in the range 112-204mg/g
      biomass.

PMID- 16997548
TI  - Dairy manure and tillage effects on soil fertility and corn yields.
AB  - Organic amendments have received renewed attention to improve soil fertility for
      crop production. A randomized complete block split plot experiment was conducted
      to evaluate the dairy manure (DM) amendments of soil for corn (Zea mays L. cv.
      Monsanto 919) production under different tillage systems. Main plot treatments
      were no-till (NT), conventional tillage (CT), and deep tillage (DT), and subplot
      treatments were chemical fertilization (DM(0)), and DM at 10Mgha(-1)yr(-1)
      (DM(10)) and 20Mgha(-1)yr(-1) (DM(20)) with supplemental chemical fertilization.
      Results show that tillage and DM had significantly reduced bulk density (rho(b))
      with greater porosity (f(t)) and hydraulic conductivity (K(fs)) than soils under
      NT and DM(0). Manuring was effective to improve soil physical properties in all
      tillage treatments. While manure significantly increased C sequestration, the N
      concentration was influenced by both tillage and manure with significant
      interaction. The CT significantly increased P as did the addition of manure.
      However, with manure, K was significantly increased in all tillage treatments.
      While tilled soils produced taller plants with higher grain yields, and water-use
      efficiency than NT soils, manuring, in contrast, increased corn harvest index.
      Manure exerted significant quadratic effect on corn biomass N and K uptake. The
      variable effects of tillage and dairy manuring on soil properties and corn growth
      are most probably related to "transitional period" in which soil ecosystems may
      have adjusting to a new equilibrium.

PMID- 16997549
TI  - Synthesis and antibacterial activity of C6-carbazate ketolides.
AB  - A novel series of ketolides containing heteroaryl groups that are linked to the
      erythronolide ring via a C6-carbazate functionality has been successfully
      synthesized. Careful modulation of the heteroaryl groups, the length and degree
      of saturation of the C6-carbazate linker, and the substituents present on each of
      the carbazate nitrogens led to compounds with potent activity against key
      bacterial respiratory pathogens. The best analogs of this series had in vitro and
      in vivo (sc dosing) profiles that were comparable to telithromycin.

PMID- 16997550
TI  - Identification of a novel boron-containing antibacterial agent (AN0128) with anti
      inflammatory activity, for the potential treatment of cutaneous diseases.
AB  - A series of borinic acid picolinate esters were synthesized and screened for
      their minimum inhibitory concentration (MIC) against Gram-positive and -negative
      bacteria. Our lead compounds were then screened for anti-inflammatory activity.
      From these studies, we identified 3-hydroxypyridine-2-carbonyloxy-bis(3-chloro-4
      methylphenyl)borane (2g, AN0128) as having the best combination of anti-bacterial
      and anti-inflammatory activities. This compound is now in clinical development
      for dermatological conditions.

PMID- 16997551
TI  - Toward a rational design of selective multi-trypanosomatid inhibitors: a
      computational docking study.
AB  - Compound V7, a benzothiazole which was recently found as selective inhibitor of
      trypanosomal TIMs, was docked into TIMs from Trypanosoma cruzi, Trypanosoma
      brucei, Entamoeba histolytica, Plasmodium falciparum, yeast, and human.
      Structural analyses revealed the importance of the accessibility to the two
      aromatic clusters located at the dimer's interface for the selective inhibition
      of trypanosomal TIMs. Thus, it was found that different accessibilities of the
      protein interface of TIMs plays an important role in the inhibitory activity of
      benzothiazoles. These findings will contribute to the rational development and
      improvement of benzothiazoles to be used as multi-trypanosomatid inhibitors.

PMID- 16997552
TI  - Isobrassinin and its analogues: novel types of antiproliferative agents.
AB  - Isobrassinin (2-(S-methyldithiocarbamoylaminomethyl)indole (7a), a regioisomer of
      the cruciferous phytoalexin brassinin (1), exerted marked antiproliferative
      effects on the HeLa, A431 and MCF7 cell lines (>78.6% inhibition at 30muM). For
      structure-activity relationships, further analogues were synthesized. The highest
      cytotoxic effect was displayed by 2-phenylimino-1,3-thiazino[5,6-b]indole (10)
      (10 microM, 76.8%-HeLa and 46.3%-MCF7). The effect of the natural phytoalexin
      brassinin was also determined.

PMID- 16997553
TI  - Redesign of aminoglycosides for treatment of human genetic diseases caused by
      premature stop mutations.
AB  - A series of new derivatives of the clinically used aminoglycoside antibiotic
      paromomycin were designed, synthesized, and their ability to read-through
      premature stop codon mutations was examined in both in vitro translation system
      and ex vivo mammalian cultured cells. One of these structures, a pseudo
      trisaccharide derivative, showed notably higher stop codon read-through activity
      in cultured cells compared to those of paromomycin and gentamicin.

PMID- 16997554
TI  - Study on synthesis and biological activity of a galactosylated piperazinyl
      porphyrin.
AB  - In order to obtain an carcinoma-selective drug, the synthesis and
      characterization of 5,10,15,20-tetra[4-(4'-galactosylpiperazinyl)phenyl]porphyrin
      (TGPP) is reported. The biological activity on cancer cells and the
      pharmacokinetics are also reported as preliminary results showing a very high
      liver to skin ratio and short retention time in tissues, and thus promising
      activity in photodynamic therapy.

PMID- 16997555
TI  - Hydroxyl radical scavenging by edaravone derivatives: Efficient scavenging by 3
      methyl-1-(pyridin-2-yl)-5-pyrazolone with an intramolecular base.
AB  - We synthesized various 3-methyl-1-phenyl-5-pyrazolone (edaravone) derivatives and
      evaluated their oxidation potential and hydroxyl radical scavenging activity. It
      was found 3-methyl-1-(pyridin-2-yl)-5-pyrazolone had a much higher ability to
      scavenge the radical than did edaravone itself. Its efficient radical scavenging
      activity was assumed to be due to the increase of its anion form, an active form,
      by a hydrogen-bonded intramolecular base.

PMID- 16997556
TI  - The development of 2-benzimidazole substituted pyrimidine based inhibitors of
      lymphocyte specific kinase (Lck).
AB  - This communication details the synthesis, biological activity, and binding mode
      of a novel class of 2-benzimidazole substituted pyrimidines. The most potent
      analogs disclosed showed low nanomolar activity for the inhibition of Lck kinase
      and a representative analog was co-crystallized with Hck (a structurally related
      member of the Src family kinases).

PMID- 16997557
TI  - Synthesis and antibacterial activity of novel neamine derivatives.
AB  - Synthesis and activity of derivatives at the O5 or O6 positions of 1-N-((S)-4
      amino-2-hydroxybutyryl)-3',4'-dideoxyneamine, which is the neamine moiety of
      arbekacin, were reported. Among these results, the 5-O-aminoethylaminocarbonyl
      derivative showed effective activity against Staphylococcus aureus expressing a
      bifunctional aminoglycoside-modifying enzyme AAC(6')-APH(2'').

PMID- 16997558
TI  - Polyoxometalates--a new class of potent ecto-nucleoside triphosphate
      diphosphohydrolase (NTPDase) inhibitors.
AB  - Polyoxotungstates were identified as potent inhibitors of NTPDases1, 2, and 3.
      The most potent compound was K(6)H(2)[TiW(11)CoO(40)], exhibiting K(i) values of
      0.140 microM (NTPDase1), 0.910 microM (NTPDase2), and 0.563 microM (NTPDase3).
      One of the compounds, (NH(4))(18)[NaSb(9)W(21)O(86)], was selective for NTPDases2
      and 3 versus NTPDase1. NTPDase inhibition might contribute to the described
      biological effects of polyoxometalates, including their anti-cancer activity.

PMID- 16997559
TI  - 5-(1H-Benzimidazol-1-yl)-3-alkoxy-2-thiophenecarbonitriles as potent, selective,
      inhibitors of IKK-epsilon kinase.
AB  - The identification and hit-to-lead exploration of a novel, potent and selective
      series of substituted benzimidazole-thiophene carbonitrile inhibitors of IKK
      epsilon kinase is described. Compound 12e was identified with an IKK-epsilon
      enzyme potency of pIC(50) 7.4, and has a highly encouraging wider selectivity
      profile, including selectivity within the IKK kinase family.

PMID- 16997560
TI  - A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I.
AB  - The design, synthesis, and enzyme kinetics evaluation of a transition-state
      inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc
      chelator with a urea isostere for the glu-cys amide bond led to a glutathione
      analog which retained inhibitory potency toward glyoxalase-I while possessing
      resistance toward gamma-glutamyltranspeptidase mediated breakdown. This compound
      is viewed as a potential lead for the development of second-generation glyoxalase
      I inhibitors wherein, the problems pertaining to metabolism and selectivity are
      overcome.

PMID- 16997561
TI  - Arm constraint and walking in healthy adults.
AB  - The aim of the present study was to examine the functional adaptations in inter
      segmental coordination when constraining one arm in healthy adults during
      treadmill walking at different velocities. Subjects were instructed to walk on a
      motorized treadmill at different walking velocities (range: 0.22-1.52 m/s) during
      three experimental conditions, i.e.: (1) no arm constraint, (2) dominant arm
      constrained, and (3) non-dominant arm constrained. Movements of body segments
      were recorded with a 3D motion analysis system. A comparison between walking with
      one arm constrained and normal walking revealed decreased, transverse pelvic,
      thoracic, and trunk rotation, however there were slight increases in non
      constrained arm movement amplitude. Reduced arm movement amplitude did result in
      altered frequency and phase relations between the arm and leg. Persons with upper
      extremity movement dysfunction may walk slower due to atypical coordination
      between upper and lower body movement at higher walking velocities. Future
      studies should focus on examining the underlying dynamics of adaptations in inter
      limb and trunk coordination during walking in both healthy adults and persons
      with upper extremity movement disorders.

PMID- 16997562
TI  - Prokaryotic photosynthesis and phototrophy illuminated.
AB  - Genome sequencing projects are revealing new information about the distribution
      and evolution of photosynthesis and phototrophy. Although coverage of the five
      phyla containing photosynthetic prokaryotes (Chlorobi, Chloroflexi,
      Cyanobacteria, Proteobacteria and Firmicutes) is limited and uneven, genome
      sequences are (or soon will be) available for >100 strains from these phyla.
      Present knowledge of photosynthesis is almost exclusively based on data derived
      from cultivated species but metagenomic studies can reveal new organisms with
      novel combinations of photosynthetic and phototrophic components that have not
      yet been described. Metagenomics has already shown how the relatively simple
      phototrophy based upon rhodopsins has spread laterally throughout Archaea,
      Bacteria and eukaryotes. In this review, we present examples that reflect recent
      advances in phototroph biology as a result of insights from genome and metagenome
      sequencing.

PMID- 16997563
TI  - Pyrinadines B-G, new bis-pyridine alkaloids with an azoxy moiety from sponge
      Cribrochalina sp.
AB  - Six new cytotoxic bis-3-alkylpyridine alkaloids with an azoxy moiety, pyrinadines
      B-G (1-6), have been isolated from an Okinawan marine sponge Cribrochalina sp.,
      and the structures were elucidated by spectroscopic data and chemical means.

PMID- 16997564
TI  - Inversion domain boundaries in ZnO with additions of Fe2O3 studied by high
      resolution ADF imaging.
AB  - Columns of metal atoms in the polytypoid compound Fe2O3(ZnO)15 could be resolved
      by high angle annular dark field imaging in a transmission electron microscopy
      (TEM)/STEM electron microscope--a result which could not be realized by high
      resolution bright field imaging due to inherent strain from inversion domains and
      inversion domain boundaries (IDBs) in the crystals. The basal plane IDB was
      imaged in [11 00] yielding the spacing of the two adjacent ZnO domains, while
      imaging in [21 1 0] yields the position of single metal ions. The images allow
      the construction of the entire domain structure including the stacking sequence
      and positions of the oxygen ions. The IDB consists of a single layer of
      octahedrally co-ordinated Fe3+ ions, and the inverted ZnO domains are related by
      point symmetry at the iron position. The FeO6 octahedrons are compressed along
      the ZnO c-axis resulting in a FeO bond length of 0.208 nm which is in the range
      of FeO distances in iron containing oxides. The model of the basal plane boundary
      resembles that of the IDB in polytypoid ZnO-In2O3 compounds.

PMID- 16997565
TI  - Coronary artery imaging with 64-slice computed tomography from cardiac surgical
      perspective.

PMID- 16997566
TI  - Menin and its interacting proteins: elucidation of menin function.
AB  - The multiple endocrine neoplasia type 1 (MEN1) gene is a tumor suppressor gene
      encoding a 610 amino acid nuclear protein, menin. Although mutations of the MEN1
      gene are responsible for MEN 1 syndrome, the intracellular functions of menin
      have not been fully elucidated. Recent data suggest that interactions between
      menin and menin-interacting proteins have a role in physiological regulation of
      cell growth, control of the cell cycle and genome stability, and are potentially
      important in bone development and multipotent mesenchymal stem cell
      differentiation. Loss of these interactions might also contribute to the
      development of MEN 1 syndrome.

PMID- 16997567
TI  - Fetal origins of breast cancer.
AB  - Susceptibility to breast cancer might be pre-determined in utero. Alterations in
      the fetal hormonal environment, caused by either maternal diet or exposure to
      environmental factors with endocrine activities, can modify the epigenome, and
      these modifications are inherited in somatic daughter cells and maintained
      throughout life. These epigenetic modifications might lead to changes in mammary
      gland development, such as increased vulnerability of epithelial targets for
      malignant transformation. According to this hypothesis, on post-pubertal exposure
      to an initiating factor, such as a carcinogen, high levels of hormones and
      radiation, the mammary epithelial targets, perhaps stem cells, in terminal end
      buds/terminal ductal lobular units would be at an increased risk of malignant
      transformation. The increased susceptibility for cancer initiation might result
      from high levels of cell proliferation, reduced apoptosis and/or altered stromal
      regulation. Thus, maternal diet and environmental exposure might increase the
      risk of breast cancer by inducing permanent epigenetic changes in the fetus that
      alter the susceptibility to factors that can initiate breast cancer. Identifying
      the epigenetically altered target genes and their ligands might lead to
      strategies to prevent this disease in some women.

PMID- 16997568
TI  - The potency of the fatty acid amide hydrolase inhibitor URB597 is dependent upon
      the assay pH.
AB  - Inhibitors of the enzyme fatty acid amide hydrolase (FAAH), the principal enzyme
      involved in the metabolism of the endogenous cannabinoid anandamide, have
      potential utility in the treatment of disorders including inflammation and
      inflammatory pain. The carbamate compound URB597 (3'-carbamoyl-biphenyl-3-yl
      cyclohexylcarbamate) potently and selectively inhibits FAAH by forming a covalent
      bond with a key serine residue of the enzyme. Little is known as to the pH
      dependency of this inhibition. Using a preincubation time of 10min, URB597
      inhibited rat brain anandamide hydrolysis with pI(50) values of 7.19+/-0.02 and
      7.75+/-0.06 at pH 6 and 8, respectively. The inhibition was time-dependent, and
      second order rate constants of approximately 0.15x10(6)M(-1)min(-1) (pH 6) and
      approximately 1.2x10(6)M(-1)min(-1) (pH 8) could be estimated. In intact C6
      glioma cells and using a preincubation time of 10min, URB597 inhibited the
      hydrolysis of 250nM [(3)H]AEA hydrolysis with pI(50) values of 5.58+/-0.07 and
      6.45+/-0.07 at extracellular pH values of 6 and 8, respectively. Since tissue pH
      is affected by inflammation, these data would suggest that the pH selectivity of
      the inhibition can contribute to the potency of the compound in vivo.

PMID- 16997570
TI  - Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular,
      and clinical features.
AB  - Mendelian susceptibility to mycobacterial diseases confers predisposition to
      clinical disease caused by weakly virulent mycobacterial species in otherwise
      healthy individuals. Since 1996, disease-causing mutations have been found in
      five autosomal genes (IFNGR1, IFNGR2, STAT1, IL12B, IL12BR1) and one X-linked
      gene (NEMO). These genes display a high degree of allelic heterogeneity, defining
      at least 13 disorders. Although genetically different, these conditions are
      immunologically related, as all result in impaired IL-12/23-IFN-gamma-mediated
      immunity. These disorders were initially thought to be rare, but have now been
      diagnosed in over 220 patients from over 43 countries worldwide. We review here
      the molecular, cellular, and clinical features of patients with inborn errors of
      the IL-12/23-IFN-gamma circuit.

PMID- 16997569
TI  - Quantitating the relative abundance of isoaspartyl residues in deamidated
      proteins by electron capture dissociation.
AB  - Relative quantitation of aspartyl and isoaspartyl residue mixtures from
      asparagine deamidation is demonstrated using electron capture dissociation
      without prior HPLC separation. The method utilizes the linear relationship found
      between the relative abundance of the isoaspartyl diagnostic ion, z(n)-57, and %
      isoaspartyl content based on the ECD spectra of known isoaspartyl/aspartyl
      mixtures of synthetic peptides. The observed linearity appears to be sequence
      independent because the relationship exists despite sequence variations and
      changes in backbone fragment abundances when isoaspartyl and aspartyl residues
      are interchanged. Furthermore, a new method to calculate the relative abundances
      of isomer from protein deamidation without synthetic peptides is proposed and
      tested using a linear peptide released by protein digestion that contains the
      deamidation site. The proteolytic peptide can be rapidly aged to the expected 3:1
      (isoaspartyl:aspartyl) mixture to generate a two-point calibration standard for
      ECD analysis. The procedure can then be used to determine the relative abundance
      of deamidation products from in vivo or in vitro protein aging experiments.

PMID- 16997571
TI  - Expression, purification and characterization of calcium-triggered luciferin
      binding protein of Renilla reniformis.
AB  - The Ca2+-triggered luciferin-binding protein of Renilla reniformis (RLBP) is a
      non-covalent complex of apoprotein (apoRLBP) and coelenterazine (luciferin). The
      gene encoding apoRLBP with 552 nucleotides has been synthesized by assembly PCR
      methods with synthetic oligonucleotides, and the histidine-tagged apoRLBP
      expressed as a soluble form in the periplasmic space of Escherichia coli cells.
      The apoRLBP was purified by nickel chelate chromatography and the procedure
      yielded 18.2mg of recombinant apoRLBP from 80 ml of cultured cells with purity
      greater than 95%. The purified apoRLBP was converted to RLBP by incubation with
      coelenterazine in the presence of dithiothreitol and the purity of recombinant
      RLBP was estimated to be over 95% by comparison with the absorption spectral data
      of native RLBP. When RLBP mixed with Ca2+, coelenterazine was dissociated from
      RLBP and was utilized for the luminescence reaction of Renilla luciferase. Also
      semi-synthetic RLBPs with h-, e-, and Bis-coelenterazines were prepared and
      characterized.

PMID- 16997572
TI  - Expression, purification and characterization of the membrane-associated HrcA
      repressor protein of Helicobacter pylori.
AB  - Helicobacter pylori, a microaerophilic, gram-negative bacterium is a human
      pathogen that colonizes the gastric niche and is associated with several acute
      and chronic stomach diseases. In order to survive in the gastric environment and
      become pathogenic, the bacterium relies on a plethora of virulence factors, which
      also include heat shock proteins. We previously showed that two out of the three
      operons encoding the major cellular chaperone machineries are transcriptionally
      repressed by two regulators, HrcA and HspR. Till now, molecular studies aimed at
      the understanding of the role of each protein in controlling transcription was
      hampered by toxicity and insolubility of HrcA in heterologous expression systems.
      Similar problems were encountered by many other groups studying HrcA from
      different bacteria. In this study, we analyzed the amino acid sequence of HrcA
      that predicted association of this protein to the inner membrane, which was
      experimentally verified. Subsequently, we implemented a dedicated induction
      protocol which enabled the overexpression of the recombinant His-HrcA protein in
      the soluble fraction of Escherichia coli cells. Moreover, we developed a
      purification procedure for His-HrcA that allowed us to obtain highly pure
      preparation of the protein. The functionality of the purified protein was then
      confirmed with an in vitro DNA-binding assay.

PMID- 16997573
TI  - Cloning and expression of the B chain of volkensin, type 2 ribosome inactivating
      protein from Adenia volkensii harms: co-folding with the A chain for heterodimer
      reconstitution.
AB  - Type 2 ribosome inactivating proteins (RIPs) include some potent plant toxins,
      among which ricin from Ricinus communis and abrin from Abrus precatorius seeds,
      have been known for more than a century. Two other type 2 RIPs belong to this
      class of proteins, both isolated from plants of the same family (Passifloraceae),
      modeccin and volkensin, from Adenia digitata and Adenia volkensii roots,
      respectively. Volkensin is probably the most potent plant toxin known, with an
      LD50 for rats of 50-60 ng/kg. Here we report the cloning, expression and
      renaturation of recombinant volkensin B chain. Furthermore, starting from
      separately expressed A and B chains, a co-association procedure was set-up,
      leading to in vitro heterodimeric volkensin reconstitution. The recombinant
      heterodimer was characterized by N-terminal sequence analysis and its
      hemagglutinating activity assessed. In parallel, we have explored the
      carbohydrate-binding properties of native volkensin with the aim to correlate
      toxin-specific properties (i.e., axonal transport along neurons) to lectin's
      sugar-binding preferences.

PMID- 16997574
TI  - Heterologous expression and site-directed mutagenesis studies of two Trichoderma
      harzianum chitinases, Chit33 and Chit42, in Escherichia coli.
AB  - Heterologous expression of two fungal chitinases, Chit33 and Chit42, from
      Trichoderma harzianum was tested in the different compartments and on the surface
      of Escherichia coli cells. Our goal was to find a fast and efficient expression
      system for protein engineering and directed evolution studies of the two fungal
      enzymes. Cytoplasmic overexpression resulted in both cases in inclusion body
      formation, where active enzyme could be recovered after refolding. Periplasmic
      expression of Chit33, and especially of Chit42, proved to be better suited for
      mutagenesis purposes. Recombinant chitinases from the periplasmic expression
      system showed activity profiles similar to those of the native proteins. Both
      chitinases also degraded a RET (resonance energy transfer) based bifunctionalized
      chitinpentaose substrate in a similar manner as reported for some putative
      exochitinases in the glycosyl hydrolase family 18, offering a sensitive way to
      assay their activities. We further demonstrated that Chit42 can also be displayed
      on E. coli surface and the enzymatic activity can be measured directly from the
      whole cells using methylumbelliferyl-chitinbioside as a substrate. The
      periplasmic expression and the surface display of Chit42, both offer a suitable
      expression system for protein engineering and activity screening in a microtiter
      plate scale. As a first mutagenesis approach we verified the essential role of
      the two carboxylic acid residues E172 (putative proton donor) and D170 (putative
      stabilizer) in the catalytic mechanism of Chit42, and additionally the role of
      the carboxylic acid E145 (putative proton donor) in the catalytic mechanism of
      Chit33.

PMID- 16997575
TI  - On the nature of 2D crystal unbending.
AB  - Crystal unbending, the process that aims to recover a perfect crystal from
      experimental data, is one of the more important steps in electron crystallography
      image processing. The unbending process involves three steps: estimation of the
      unit cell displacements from their ideal positions, extension of the deformation
      field to the whole image and transformation of the image in order to recover an
      ideal crystal. In this work, we present a systematic analysis of the second step
      oriented to address two issues. First, whether the unit cells remain undistorted
      and only the distance between them should be changed (rigid case) or should be
      modified with the same deformation suffered by the whole crystal (elastic case).
      Second, the performance of different extension algorithms (interpolation versus
      approximation) is explored. Our experiments show that there is no difference
      between elastic and rigid cases or among the extension algorithms. This implies
      that the deformation fields are constant over large areas. Furthermore, our
      results indicate that the main source of error is the transformation of the
      crystal image.

PMID- 16997576
TI  - Observing complex action sequences: The role of the fronto-parietal mirror neuron
      system.
AB  - A fronto-parietal mirror neuron network in the human brain supports the ability
      to represent and understand observed actions allowing us to successfully interact
      with others and our environment. Using functional magnetic resonance imaging
      (fMRI), we wanted to investigate the response of this network in adults during
      observation of hierarchically organized action sequences of varying complexity
      that emerge at different developmental stages. We hypothesized that fronto
      parietal systems may play a role in coding the hierarchical structure of object
      directed actions. The observation of all action sequences recruited a common
      bilateral network including the fronto-parietal mirror neuron system and occipito
      temporal visual motion areas. Activity in mirror neuron areas varied according to
      the motoric complexity of the observed actions, but not according to the
      developmental sequence of action structures, possibly due to the fact that our
      subjects were all adults. These results suggest that the mirror neuron system
      provides a fairly accurate simulation process of observed actions, mimicking
      internally the level of motoric complexity. We also discuss the results in terms
      of the links between mirror neurons, language development and evolution.

PMID- 16997577
TI  - Neural activation to upright and inverted faces in infants measured by near
      infrared spectroscopy.
AB  - The present study examined infants' brain activity in response to upright and
      inverted faces using near infrared spectroscopy (NIRS), which can non-invasively
      record hemodynamic changes of the brain. NIRS is particularly useful for
      recording in infants, since recordings can be made, even while the infants are
      awake, without fixing their body and brain. For this objective, we used newly
      developed sensor probes of NIRS for recording in infants. We measured changes in
      cerebral oxygenation in 10 5-8-month-olds' left and right lateral areas while
      they were looking at upright and inverted faces. The results are summarized as
      follows: (1) the concentration of oxyhemoglobin (oxy-Hb) and total hemoglobin
      (total-Hb) increased significantly in the right lateral area during the upright
      face condition, (2) the concentration of total-Hb in the right lateral area
      differed significantly between the upright and inverted conditions, (3)
      hemodynamic changes were maximal in the temporal region, probably in the superior
      temporal sulcus (STS) in both hemispheres, and (4) the right hemisphere seems to
      be more important for recognizing upright faces. This is the first evidence
      showing that there is an inter-hemispheric difference on the effect of face
      inversion in the infant brain using a hemodynamic method.

PMID- 16997578
TI  - Simulating deformations of MR brain images for validation of atlas-based
      segmentation and registration algorithms.
AB  - Simulated deformations and images can act as the gold standard for evaluating
      various template-based image segmentation and registration algorithms.
      Traditional deformable simulation methods, such as the use of analytic
      deformation fields or the displacement of landmarks followed by some form of
      interpolation, are often unable to construct rich (complex) and/or realistic
      deformations of anatomical organs. This paper presents new methods aiming to
      automatically simulate realistic inter- and intra-individual deformations. The
      paper first describes a statistical approach to capturing inter-individual
      variability of high-deformation fields from a number of examples (training
      samples). In this approach, Wavelet-Packet Transform (WPT) of the training
      deformations and their Jacobians, in conjunction with a Markov random field (MRF)
      spatial regularization, are used to capture both coarse and fine characteristics
      of the training deformations in a statistical fashion. Simulated deformations can
      then be constructed by randomly sampling the resultant statistical distribution
      in an unconstrained or a landmark-constrained fashion. The paper also describes a
      model for generating tissue atrophy or growth in order to simulate intra
      individual brain deformations. Several sets of simulated deformation fields and
      respective images are generated, which can be used in the future for systematic
      and extensive validation studies of automated atlas-based segmentation and
      deformable registration methods. The code and simulated data are available
      through our Web site.

PMID- 16997579
TI  - Reliable detection of bilateral activation in human primary somatosensory cortex
      by unilateral median nerve stimulation.
AB  - In non-human primates, a bilateral representation of unilaterally presented
      somatosensory information can be found at the lowest level of cortical processing
      as indicated by the presence of neurons with bilateral receptive fields in the
      hand region of primary somatosensory (SI) cortex. In humans, such bilateral
      activation of SI is considered controversial due to highly variable detection
      rates for the much weaker ipsilateral response across different studies (ranging
      from 3% to 100%). Second-order blind identification (SOBI) is a blind source
      separation algorithm that has been successfully used to isolate neuronal signals
      from functionally distinct brain regions, including the left- and right-SI. SOBI
      aided extraction of left- and right-SI responses to median nerve stimulation from
      high-density EEG has been previously validated against the fMRI and MEG
      literature. Here, we applied SOBI to EEG data and examined whether relatively
      weaker ipsilateral activations could be reliably detected across subjects. In
      single subject analysis, statistically significant somatosensory evoked
      potentials (SEPs) in response to unilateral stimulation were detected from both
      SI contralateral to and SI ipsilateral to the side of stimulation. Furthermore,
      these ipsilateral responses were observed in both the left and right hemispheres
      of all 10 subjects studied. Together these results demonstrate that unilateral
      stimulation of the median nerve, whether applied to the left or right wrist, can
      activate both the left- and right-SI, raising the possibility that in humans,
      unilateral sensory input may be bilaterally represented at the lowest level of
      cortical processing.

PMID- 16997580
TI  - Developmental neural networks in children performing a Categorical N-Back Task.
AB  - The prefrontal and temporal networks subserving object working memory tasks in
      adults have been reported as immature in young children; yet children are
      adequately capable of performing such tasks. We investigated the basis of this
      apparent contradiction using a complex object working memory task, a Categorical
      n-back (CN-BT). We examined whether the neural networks engaged by the CN-BT in
      children consist of the same brain regions as those in adults, but with a
      different magnitude of activation, or whether the networks are qualitatively
      different. Event-related fMRI was used to study differences in brain activation
      between healthy children ages 6 and 10 years, and young adults (20-28 years).
      Performance accuracy and RTs in 10-year-olds and adults were comparable, but the
      performance in 6-year-olds was lower. In adults, the CN-BT was highly effective
      in engaging the bilateral (L>R) ventral prefrontal cortex, the bilateral fusiform
      gyrus, posterior cingulate and precuneus, thus suggesting an involvement of the
      ventral visual stream, with related feature extraction and semantic labeling
      strategies. In children, the brain networks were distinctly different. They
      involved the premotor and parietal cortex, anterior insula, caudate/putamen, and
      the cerebellum, thus suggesting a predominant involvement of the visual dorsal
      and sensory-motor pathways, with related visual-spatial and action cognitive
      strategies. The findings indicate engagement of developmental networks in
      children reflecting task-effective brain activation. The age-related pattern of
      fMRI activation suggests a working hypothesis of a developmental shift from
      reliance on the dorsal visual stream and premotor/striatal/cerebellar networks in
      young children to reliance on the ventral prefrontal and inferior temporal
      networks in adults.

PMID- 16997581
TI  - A penalty of using anonymous dominant markers (AFLPs, ISSRs, and RAPDs) for
      phylogenetic inference.
AB  - AFLPs (and to a lesser extent ISSRs and RAPDs) are increasingly being used for
      phylogenetic inference among closely related species. Presence/absence characters
      for each AFLP allele treat all absences as homologous to one another. With three
      or more alleles, terminals are grouped by their shared absence of alleles in
      character-based phylogenetic-inference methods in a manner that is not redundant
      with their shared presence of an alternative allele. We conducted simulations to
      quantify how severe the negative effect of using presence/absence characters of
      individual bands is for phylogenetic inference relative to standard multistate
      characters. We examined alternative tree topologies, relative branch lengths,
      numbers of characters, rates of evolution, and numbers of alternative alleles,
      using both parsimony and Nei-and-Li distance analyses. Multistate parsimony
      generally outperformed presence/absence parsimony, which in turn outperformed Nei
      and-Li distance. Increasing the character-state space (i.e., the number of
      alternative character states available) was found to be advantageous for all
      three methods of analysis examined, but was most advantageous for multistate
      parsimony. However, the advantage of multistate parsimony relative to Nei-and-Li
      distance decreased when applied to more divergent characters. More parsimony
      informative variation generally alleviated the problem associated with scoring
      multistate characters as presence/absence characters. The ensemble consistency
      index was lower for presence/absence characters relative to multistate
      characters.

PMID- 16997582
TI  - Constraints in naming parts of the Tree of Life.
AB  - There are now overlapping codes of nomenclature that govern some of the same
      names of biological taxa. The International Code of Zoological Nomenclature
      (ICZN) uses the non-evolutionary concept of a "type species" to fix the names of
      animal taxa to particular ranks in the nomenclatural hierarchy. The PhyloCode, in
      contrast, uses phylogenetic definitions for supraspecific taxa at any
      hierarchical level within the Tree of Life (without associating the names to
      particular ranks), but does not deal with the names of species. Thus, biologists
      who develop classifications of animals need to use both systems of nomenclature,
      or else operate without formal rules for the names of some taxa (either species
      or many monophyletic groups). In addition, the ICZN does not permit the unique
      naming of many taxa that are considered to be between the ranks of genus and
      species. Hillis and Wilcox [Hillis, D.M., Wilcox, T.P., 2005. Phylogeny of the
      New World true frogs (Rana). Mol. Phylogenet. Evol. 34, 299-314] provided
      recommendations for the classification of New World true frogs that utilized the
      ICZN to provide names for species, and the PhyloCode to provide names for
      supraspecific taxa. Nonetheless, they created new taxon names that followed both
      sets of rules, to avoid conflicting classifications. They also recommended that
      established names for both species and clades be used whenever possible, to
      stabilize the names of both species and clades under either set of rules, and to
      avoid conflicting nomenclatures. Dubois [Dubois, A., 2006. Naming taxa from
      cladograms: a cautionary tale. Mol. Phylogenet. Evol., 42, 317-330] objected to
      these principles, and argued that the names provided by Hillis and Wilcox
      [Hillis, D.M., Wilcox, T.P., 2005. Phylogeny of the New World true frogs (Rana).
      Mol. Phylogenet. Evol. 34, 299-314] are unavailable under the ICZN, and that the
      two nomenclatural systems are incompatible. Here, I argue that he is incorrect in
      these assertions, and present arguments for retaining the established names of
      New World true frogs, which are largely compatible under both sets of
      nomenclatural rules.

PMID- 16997583
TI  - Capillary microscopy and hemorheology in children during antiepileptic
      monotherapy with carbamazepine and valproate.
AB  - The interactions of epilepsy and antiepileptic therapy an one hand and
      cardiovascular system on the other hand are multiple and complex. Antiepileptic
      drugs (AEDs) cause alterations of serum lipids and of the fatty acid composition
      of the membranes. Homocystein, known to induce vascular endothelial damage was
      found to be elevated in patients on valproate (VPA) and carbamazepine (CBZ)
      therapy. Marked coronary artherosclerosis and myocardial infarction may already
      occur in children treated with CBZ. Community based studies corroborated a higher
      incidence of myocardial infarction, peripheral vascular diseases
      hypercholesterinemia, left ventricle hypertrophy and stroke in patients with
      epilepsy. In this context, we wanted to elevate changes of microcirculation
      related to AEDs commonly prescribed such as VPA and CBZ. Capillary microscopy is
      a non-invasive technique for measuring the velocity of red blood cells and for
      determining nutritional blood flow in the capillaries of the skin. It can easily
      be performed in children. The aim of this study was to look for possible effects
      an antiepileptic monotherapy with carbamazepine or valproate has on the
      peripheral microcirculation in epileptic children. We were able to examine 14
      children with CBZ and 24 children with VPA, recruited in our neuropediatric Unit.
      The results were compared to normative values, determined in former analyses of
      207 healthy children. We found significant differences in capillary density,
      tortuous index of the capillaries, capillary diameter and flow rate of
      erythrocytes for both antiepileptic drugs. Additionally, there were changes in
      plasma viscosity and the aggregation of erythrocytes. These microcapillary
      effects could be of special interest in the relationship of a long-term
      antiepileptic therapy and the development of vascular diseases. We suggest that
      the influence of AEDs on microcirculation should also be considered in further
      studies on cardiovascular changes in patients with antiepileptic long-term
      medication.

PMID- 16997584
TI  - MMP and non-MMP-mediated release of aggrecan and its fragments from articular
      cartilage: a comparative study of three different aggrecan and glycosaminoglycan
      assays.
AB  - OBJECTIVE: Aggrecan is the major proteoglycan in articular cartilage and is known
      to be degraded by various proteases, including matrix metalloproteinases (MMPs).
      The present study was undertaken to develop immunoassays detecting aggrecan and
      its fragments generated by MMP and non-MMP-mediated proteolysis. METHODS: Two
      immunoassays were developed: (1) the G1/G2 sandwich assay employing a monoclonal
      antibody (F-78) both as a capturing and a detecting antibody, and (2) the 342-G2
      sandwich assay substituting the capturing antibody in the G1/G2 test with a
      monoclonal antibody, AF-28 recognizing the 342FFGVG neo-epitope generated by MMP
      cleavage. These assays were compared to the commercially available
      glycosaminoglycan (GAG) assay. RESULTS: In supernatants of Oncostatin M and Tumor
      Necrosis Factor alpha (OSM/TNFalpha) stimulated explants, high levels of G1/G2
      fragments and GAGs were released in the initial phase (days 2-5), followed by low
      levels in the intermediate (days 9-12) and late phase (days 12-21). MMP-generated
      fragments were detected in the late phase only. In the presence of the general
      MMP inhibitor GM6001, 342-G2 was not detected, whereas the G1/G2 profile remained
      virtually unchanged. In patients with rheumatoid arthritis (RA), the release of
      G1/G2 molecules was decreased (27.3%), and that of the 342-G2 fragments increased
      compared to healthy controls (33.3%). CONCLUSION: The stimulation of bovine
      articular cartilage explants with OSM/TNFalpha released aggrecan fragments both
      in an MMP and non-MMP-mediated route. These immunoassays carry a potential as
      diagnostic tools for the quantitative assessment of the cartilage turnover in RA
      patients in addition to their utility in ex vivo explant cultures.

PMID- 16997585
TI  - Glucocorticoid-mediated effects of systemic oxytocin upon memory retrieval.
AB  - During the last decade, a considerable amount of evidence has accumulated to show
      that oxytocin (OT) is involved with functions other than its classical roles in
      reproduction-associated processes, such as social recognition, maternal behavior
      and neuroendocrine regulation of the stress response. It has been shown, for
      instance, that post-training systemic administration of oxytocin in mice produces
      an amnestic effect on the step-through inhibitory avoidance. Since it is still
      unclear how systemic levels of OT may affect CNS memory processes, our aim here
      was to investigate the hypothesis that systemic OT effects on memory retrieval
      might be mediated through an oxytocin-induced decrease in glucocorticoid release.
      In our first experiment, we have found an amnestic effect of i.p. pre-test 0.4
      microg/kg of OT upon memory retrieval in the inhibitory avoidance task (IA); this
      OT dose was shown to (a) significantly decrease plasma corticosterone levels when
      compared to the saline group, and (b) not to cause any anxiety effects by itself
      in a plus-maze task. At last, an ineffective-by-itself dose of dexamethasone was
      able to reverse the amnestic effect of this OT dose. Our results suggest that the
      amnestic effect of systemically administered oxytocin upon memory retrieval in
      the inhibitory avoidance task was probably caused by an oxytocin-induced decrease
      in glucocorticoid release from the adrenal gland.

PMID- 16997586
TI  - Sensitivity enhanced recoupling experiments in solid-state NMR by gamma
      preparation.
AB  - In this paper, we introduce a class of dipolar recoupling experiments under magic
      angle spinning (MAS), which use gamma dependent antiphase polarization during the
      t1 evolution period. We show that this helps us to design dipolar recoupling
      experiments that transfer both components of the transverse magnetization of spin
      S to a coupled spin I in the mixing step of a 2D NMR experiment. We show that it
      is possible to design such transfer schemes and make them insensitive to the
      orientation dependency of the couplings in powders. This helps us to develop
      sensitivity enhanced 2D NMR experiments of powder samples under MAS.

PMID- 16997587
TI  - Assigning solid-state NMR spectra of aligned proteins using isotropic chemical
      shifts.
AB  - A method for assigning solid-state NMR spectra of membrane proteins aligned in
      phospholipid bicelles that makes use of isotropic chemical shift frequencies and
      assignments is demonstrated. The resonance assignments are based on comparisons
      of 15N chemical shift differences in spectra obtained from samples with their
      bilayer normals aligned perpendicular and parallel to the direction of the
      applied magnetic field.

PMID- 16997588
TI  - A simple method for protein structural classification.
AB  - Since the concept of structural classes of proteins was proposed, the problem of
      protein classification has been tackled by many groups. Most of their
      classification criteria are based only on the helix/strand contents of proteins.
      In this paper, we proposed a method for protein structural classification based
      on their secondary structure sequences. It is a classification scheme that can
      confirm existing classifications. Here a mathematical model is constructed to
      describe protein secondary structure sequences, in which each protein secondary
      structure sequence corresponds to a transition probability matrix that
      characterizes and differentiates protein structure numerically. Its application
      to a set of real data has indicated that our method can classify protein
      structures correctly. The final classification result is shown schematically. So
      it is visual to observe the structural classifications, which is different from
      traditional methods.

PMID- 16997589
TI  - Design, construction and performance of the most efficient biomass producing E.
      coli bacterium.
AB  - Inverse metabolic engineering based on elementary mode analysis was applied to
      maximize the biomass yield of Escherchia coli MG1655. Elementary mode analysis
      was previously employed to identify among 1691 possible pathways for cell growth
      the most efficient pathway with maximum biomass yield. The metabolic network
      analysis predicted that deletion of only 6 genes reduces the number of possible
      elementary modes to the most efficient pathway. We have constructed a strain
      containing these gene deletions and we evaluated its properties in batch and in
      chemostat growth experiments. The results show that the theoretical predictions
      are closely matched by the properties of the designed strain.

PMID- 16997590
TI  - Distribution of hepatitis C virus infection in the male Turkish population.

PMID- 16997592
TI  - A population-based assessment of the disease burden of consolidated pneumonia in
      hospitalized children under five years of age.
AB  - BACKGROUND: Population-based studies on childhood community-acquired pneumonia
      are scarce in Latin America. Pneumococcal epidemiology is poorly defined, hence
      the World Health Organization recommended standardized chest radiograph
      interpretation to improve the approach to bacterial pneumonia. Therefore, our
      study aimed to estimate the burden of pneumonia in hospitalized children.
      METHODS: A three-year surveillance study was carried out in four hospitals
      covering a population of 229,128 inhabitants of whom 10.2% were under five years
      of age. Clinical records and digitization of their chest radiographs were
      obtained. A pediatrician and a pediatric radiologist blinded to the clinical
      diagnosis interpreted the digital images. RESULTS: Of 2034 patients, 826 (40.6%)
      had consolidated pneumonia, 941 (46.3%) had non-consolidated pneumonia, and 267
      (13.1%) had no pneumonia. Children under two years of age predominated (66.9%).
      The average annual incidence rate for consolidated pneumonia over the three-year
      study period was 1175/10(5). Eighteen invasive Streptococcus pneumoniae were
      isolated from patients with consolidated pneumonia and two from those with non
      consolidated pneumonia. Respiratory syncytial virus was evenly distributed
      between both X-ray groups. CONCLUSIONS: Patients younger than two years of age
      predominated, being the main targets for anti-pneumococcal conjugated vaccines.
      Incidence rates provided evidence of the burden of consolidated pneumonia for
      childhood, estimating the potential benefits of vaccination.

PMID- 16997591
TI  - Oropharyngeal colonization by Streptococcus pneumoniae among HIV-infected adults
      in Uganda: assessing prevalence and antimicrobial susceptibility.
AB  - OBJECTIVES: To evaluate characteristics of Streptococcus pneumoniae associated
      with oropharyngeal colonization in the Ugandan adult HIV population. METHODS: We
      conducted a cross-sectional study at the outpatient HIV clinic at the Joint
      Clinical Research Centre in Kampala, Uganda between July 2004 and February 2005.
      Six hundred HIV-infected individuals were interviewed and had oropharyngeal
      specimens collected. Pneumococci were isolated from these specimens and
      antimicrobial susceptibility patterns determined using standard microdilution
      methods. Serotypes of the pneumococcal isolates were evaluated by capsular
      swelling reaction with commercial antisera. RESULTS: The prevalence of
      oropharyngeal colonization with pneumococci was 18% (108/600). Thirty-two
      different pneumococcal serotypes were identified, and the most common were
      serotypes 3 (14.7%), 19F (6.4%), 23F (6.4%), and 16 (5.5%). Seventy-two percent
      of the isolates were penicillin (PCN) intermediate (MICs 0.12-1 microg/mL), the
      remainder all being PCN susceptible, and >99% were trimethoprim-sulfamethoxazole
      (TMP-SMX) resistant. Novel PCN intermediate serotypes included 7, 11, 16, 20, 22,
      24, and 34. Only one isolate was resistant to macrolides, and resistance to other
      antibiotics was rare. CONCLUSIONS: HIV-infected adults in Uganda are colonized
      with pneumococci that exhibit a high degree of TMP-SMX and PCN non
      susceptibility, with several unique PCN non-susceptible serotypes that are not
      included in current vaccine preparations.

PMID- 16997593
TI  - Risk factors for shigellosis in Thailand.
AB  - OBJECTIVES: To assess the potential risk factors for shigellosis including
      housefly density. METHODS: A matched case-control study to investigate potential
      risk factors for shigellosis was conducted in a semi-urban area, Kaengkhoi
      District, Saraburi Province, central Thailand. Shigella cases were ascertained
      from a two-year population-based surveillance study detecting diarrhea and
      shigellosis in the area. The study evaluated a wide range of exposures, which
      were assessed by odds ratios (OR) adjusted for proxy markers of socioeconomic
      status: family income, and type of residence, using conditional logistic
      regression analysis. RESULTS: Hygiene behaviors such as regular hand washing
      (p<0.05), a clean environment surrounding the household (p<0.001), and the
      availability of water to flush the toilet (p=0.08) were associated with a reduced
      risk for shigellosis in the multivariate model. In contrast factors indicating a
      lower than average socioeconomic status, such as having to rent instead of owning
      one's housing (p<0.001) and a low family income (p<0.01) were associated with an
      increased risk for shigellosis. For children, breastfeeding showed a strong
      protective effect in reducing the risk of shigellosis (p<0.01). Prior to
      adjustment for environmental factors, fly density in the kitchen area was
      associated with an increased risk of shigellosis (p<0.01). CONCLUSIONS: We found
      a correlation between socioeconomic status and the risk for shigellosis. To
      reduce shigellosis in this setting, we recommend interventions focused on three
      aspects: improved water supply and sanitation (especially latrines and garbage
      disposal) including fly control, health education on hand washing, and the
      promotion of breastfeeding.

PMID- 16997594
TI  - [Red blood cell antibody screening: error analysis in a french interlaboratory
      comparison program survey].
AB  - The French quality control is organized by the French Health Products Safety
      Agency. In 2005, the immuno-haematology testing control included the screening of
      an anti KEL 1 antibody. 17 out of 2639 laboratories (0,64%) answered 'negative
      screening'. All laboratories received a questionnaire in order to understand the
      failure. In this paper the authors present the detailed laboratories' responses
      and failure explanations.

PMID- 16997596
TI  - [Air breath control radiotherapy in severe insufficiency respiratory patients
      with NSCL: application for deformable registration method in thoracic
      radiotherapy].
AB  - PURPOSE: Using deformable registration methods from a phase two clinical study of
      air breath control during radiotherapy in patients suffering from severe
      respiratory insufficiency and non-small cell lung carcinoma. PATIENTS AND
      METHODS: Between April 2002 and November 2005, 22 patients with severe
      respiratory insufficiency were treated with curative intent by conformal therapy
      combined with active breathing control. RESULTS: After a mean of follow-up of 22
      months, the local control rate is 28% and the method is feasible despite the
      severe respiratory insufficiency. However the overall survival is still poor due
      to metastatic widespread. For the second part of the study, the clinical protocol
      was also used for two studies using deformable registration methods. In the first
      study, a deformable registration method has been developed in order to register
      several breath-hold 3D CT of the same patient acquired at several days of
      interval. It allowed quantifying the interfraction breath-hold reproducibility by
      analysing the resulting displacement field. For 6 patients, the breath-hold was
      effective, while for 2 patients, motion greater than 10 mm were detected. The
      second study aimed to simulate 4D images from 3D breath-hold images. Developing
      an ad-hoc methodology based on the interpolation of 3D dense deformation fields
      performed it. The approach has been validated with expert selected landmarks,
      with accuracy lower than 3 mm. CONCLUSION: ABC is feasible, even in case of
      severe insufficiency respiratory syndrome but metastatic widespread disease is
      still a major challenge even with an acceptable local control rate without
      serious side effects: regarding the deformable registration method. Such
      artificial 4D images could allow decreasing the dose need to acquire a full 4D
      image, to simulate irregular breathing pattern and to be used for 4D dosimetry
      planning.

PMID- 16997595
TI  - [Validation of antibody screening by indirect antigloblin test and ABO blood
      typing by filtration and microplate techniques: assessment of robustness].
AB  - According to requirements of the French Committee for Accreditation (Cofrac), it
      is essential to use validated and standardised methods in Immunohematology. This
      imposes first the knowledge of metrological tolerances for all the technics. Two
      multicenter studies were carried out to define the maximal acceptable deviations
      concerning incubation temperature and time, volumes of patient plasma and tests
      cells for antibody screening using indirect antiglobulin test on one hand and for
      reverse grouping on another hand. All equipment used (temperature test chamber,
      chronometer, pipettes) were calibrated according to Cofrac standards. The
      antibody screenings were performed manually using 3 different filtration systems:
      ID Diamed, Biovue Ortho and Scangel Biorad, the same tests cells, a standard 20
      ng/mL anti RH1, a positive control anti KEL1 and a negative control; the reverse
      blood grouping was performed manually using the above mentionned filtration
      systems and microplate technic with the same A1 and B test cells. These two
      studies showed that all the tests from the multiples combinations of the above
      parameters gave the same results and allowed us to define a range of tolerance
      for 4 critical physical parameters involved in the antibody screening and blood
      typing.

PMID- 16997597
TI  - [Comparative study and clinical implementation of two breathing-adapted
      radiotherapy techniques: dosimetric benefits for lung cancer treatment].
AB  - Breathing can lead to organ motions up to several centimeters. For radiotherapy
      of lung, these motions are generally taken into account by adding a specific
      margin around the target. Thus, treated volumes are often too large to allow for
      the high-dose values requested for local control. To manage respiratory motion,
      deep-inspiration breath-hold technique (DIBH) and gated radiotherapy are starting
      being used clinically. DIBH consists in asking the patient to perform breath-hold
      during the treatment and the image acquisition, DIBH level being measured by a
      spirometer. Gated radiotherapy consists in treating the patient at a certain
      phase of the free breathing. Linac is synchronized with the motion of a marker
      located on the patient chest. Planning images are obtained by a four-dimensional
      CT (4D-CT) using the same marker. We have assessed the value of these two
      methods. For lung treatment, compared to a standard treatment, toxicity reduction
      was mainly due to the lung total volume increase. It is therefore more
      significant for breath-hold approach. It is also due to the reduction of safety
      margins, which is similar for both methods. These two techniques, which have
      specific advantages and drawbacks, are used routinely at Curie Institute for a
      large proportion of lung patients, but also for some breast, liver or even
      Hodgkin disease treatments.

PMID- 16997598
TI  - Quorum sensing affects virulence-associated proteins F1, LcrV, KatY and pH6 etc.
      of Yersinia pestis as revealed by protein microarray-based antibody profiling.
AB  - Protein microarray that consists of virulence-associated proteins of Yersinia
      pestis is used to compare antibody profiles elicited by the wild-type and quorum
      sensing (QS) mutant strain of this bacterium to define the immunogens that are
      impacted by QS. The results will lead the way for future functional proteomics
      studies. The antibody profile that was induced by the QS mutant differed from
      that of the parent strain. Detailed comparison of the antibody profiles,
      according to the proteins' functional annotations, showed that QS affects the
      expression of many virulence-associated proteins of Y. pestis. The antibodies to
      many virulence-associated proteins were not detected or lower titers of
      antibodies to many proteins were detected in the sera of rabbits immunized with
      the QS mutant, relative to those of the wild type, which indicated that these
      proteins were not expressed or expressed at relatively lower levels in the QS
      mutant. The results demonstrated that antibody profiling by protein microarrays
      is a promising high-throughput method for revealing the interactions between
      pathogens and the host immune system.

PMID- 16997599
TI  - Use of tumor necrosis factor inhibitors in rheumatoid arthritis: a national
      survey of practicing United States rheumatologists.
AB  - OBJECTIVES: To determine the prescribing practices, laboratory monitoring
      protocols, and perceived barriers of United States rheumatologists in prescribing
      tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA). METHODS: A
      survey questionnaire was mailed to 1970 rheumatologists who were randomly
      selected from a national sample of 3008 rheumatologists. A one-page non-response
      questionnaire was mailed to approximately 200 randomly selected non-responding
      rheumatologists to assess non-response bias. RESULTS: Two mailings yielded a
      response rate of 22.3% (428 completed, usable surveys out of 1922 deliverable
      surveys). Rheumatologists reported using all three agents in patients with
      moderate RA (82-87%), severe RA (94-96%), and in newly diagnosed and mild RA
      patients (10-18%). In patients with severe RA who inadequately responded to
      methotrexate, 91% of rheumatologists reported using a TNF inhibitor with one
      other disease modifying anti-rheumatic drug. Over 94% of rheumatologists reported
      switching patients from one TNF inhibitor to a different TNF inhibitor due to
      inadequate response or side effects. Most rheumatologists (96%) ordered the
      purified protein derivative test for tuberculosis, with almost 82% conducting
      this test at baseline. Costs to patients and insurance coverage were perceived as
      major barriers to prescribing these agents although the perception was slightly
      lower with infliximab than with adalimumab or etanercept. CONCLUSIONS: The use of
      TNF inhibitors is not restricted to patients with moderate and severe RA.
      Rheumatologists are fairly similar in their utilization of the three TNF
      inhibitors although some variation exists in terms of laboratory practices and
      perceived barriers regarding the use of these agents.

PMID- 16997600
TI  - Posterior spinal epidural abscess: an unusual complication of vertebroplasty.
AB  - OBJECTIVE: Complications after vertebroplasty are rare. There are few reported
      infectious complications requiring surgical management such as corpectomy with
      anterior reconstruction and posterior stabilization, although we have not seen
      any reports about epidural abscess in the literature. We present a patient in
      whom posterior epidural abscess developed after vertebroplasty in which drainage
      and antibiotherapy were required for treatment. METHODS: A 70-year-old female
      with a painful T12 osteoporotic compression fracture underwent percutaneous
      vertebroplasty using polymethylmethacrylate without complication. One week after
      vertebroplasty, however, she had fever and increased back pain. On clinical
      examination, soft tissue abscess formation was determined at the vertebroplasty
      site. This was drained surgically and antibiotic treatment was started. At follow
      up, she had progressive neurological deterioration (paraparetic) on the 18th day
      after abscess drainage. MRI of the thoracolombar spine revealed posterior spinal
      epidural abscess at the T11/12 level. Partial laminectomy and drainage were
      performed. She had complete neurological recovery in the follow-up period.
      CONCLUSION: An epidural abscess, which is an unusual complication of
      vertebroplasty, represents a medical and surgical emergency. Treatment is
      generally urgent surgical drainage combined with antibiotics. The patient should
      be evaluated in detail for systemic infectious disease and comorbid conditions
      before the vertebroplasty procedure.

PMID- 16997601
TI  - Symptomatic polyostotic fibrous dysplasia of the thoracic spine.
AB  - We present a case of polyostotic fibrous dysplasia with limited involvement in
      thoracic spine and adjacent ribs. The patient underwent posterior instrumentation
      performed between Th3 and Th11 with pedicle screw system, followed by
      costotransversectomy of 7th and 8th costovertebral junctions and posterior spinal
      fusion for costal lesions. In the same operation, curettage was done for the
      lesion in Th6 vertebra and bone grafting and anterior total corpectomy were
      performed for Th7 and Th8 vertebrae. 360 degrees spinal fusion was done using
      titanium mesh as strut graft and autogenous rib grafts. Fibrous dysplasia occurs
      rarely in axial bones than peripheral bones. The cystic lesions in segments of
      the whole spine should be evaluated for the possibility of fibrous dysplasia with
      detailed radiographical examination and biopsy.

PMID- 16997602
TI  - Clinical response to intra-articular injections of hylan G-F 20 in symptomatic
      hip osteoarthritis: the OMERACT-OARSI criteria applied to the results of a pilot
      study.
AB  - OBJECTIVE: To assess, using the OMERACT-OARSI criteria, the clinical response of
      patients presenting with symptomatic hip osteoarthritis (OA) to one intra
      articular injection of hylan G-F 20. METHODS: Open-label, multi-centre,
      prospective, pilot study. Fifty-six patients presenting with primary hip OA,
      Kellgren-Lawrence grade II-III, age > or =40, with walking pain measuring 50-90
      mm on a 100 mm visual analogue scale (VAS). Intra-articular injection of a single
      2 ml dose of hylan G-F 20 into the hip joint under fluoroscopic guidance. A
      second injection could be administered at day (D) 30, 60 or 90 if pain was
      unchanged or returned to baseline levels. EFFICACY CRITERIA: The outcome of the
      first injection in the intent-to-treat (ITT) population was analysed 90 days
      after the injection in those patients that received a single injection, and on
      the day of the second injection in those patients that required two injections,
      using OMERACT-OARSI responder criteria (obtained from WOMAC A and C indices and
      the patient's global evaluation) and variation in walking pain on VAS. RESULTS:
      The percentage of responders according to the OMERACT-OARSI response criteria was
      53.6%. An inverse correlation was observed between reduction in pain and joint
      space narrowing score (P=0.03). CONCLUSION: In the absence of a control group,
      the efficacy of the treatment cannot be determined conclusively. Nevertheless
      these data suggest that hylan G-F 20 is a symptomatic treatment of hip OA,
      particularly in less severe radiological cases. A double-blind, controlled study
      is required to confirm these data.

PMID- 16997603
TI  - New indications for botulinum toxin in rheumatology.
AB  - Previously known only as a deadly bacterial poison responsible for severe
      paralysis, botulinum toxin is now a well-recognized therapeutic agent used to
      relieve involuntary movements, dystonia-related functional impairments,
      spasticity, and autonomic disorders such as hyperhidrosis. Musculoskeletal pain
      in patients with rheumatic disorders is among the emerging indications for
      botulinum toxin therapy. Preliminary data have been obtained in patients with
      cervical or thoracolumbar myofascial pain syndrome, chronic low back pain,
      piriformis muscle syndrome, tennis elbow, and stiff person syndrome. At present,
      the effects of botulinum toxin and its use for pain relief remain controversial.
      Carefully designed prospective trials are needed to investigate the efficacy and
      safety of botulinum toxin in pain disorders.

PMID- 16997604
TI  - Arthrography in loosened hip prostheses. Assessment of possibilities for intra
      articular therapy.
AB  - BACKGROUND: Loosening is a major complication in prosthesis surgery. Less
      invasive alternatives to revision surgery are required to prevent and treat
      prosthesis loosening. Some experimental therapies investigating alternative
      treatments exploit the intra-articular space as a route of administration. For
      efficient, local delivery of therapeutic agents a contained joint space is
      required. Furthermore, the volume of the joint space determines the concentration
      of the therapeutic ingredient in the joint. METHODS: A retrospective analysis of
      221 hip arthrograms performed between 1994 and 2004 for diagnosis of prosthesis
      loosening was performed. All arthrograms were studied for leakage of contrast
      medium and the volume of injected contrast medium. RESULTS: There was a contained
      joint in 164 arthrograms (74%). The volume in these hips was 31+/-12.7 ml. Male
      patients had a larger joint volume than female patients (P=0.019). There was no
      difference in containment and joint volume between hips with a primary and with a
      revised prosthesis. CONCLUSIONS: For successful intra-articular therapy it is
      necessary that the injected agent remains in the jointspace. As leakage of
      contrast medium was shown in about a quarter of hips, this study shows that an
      arthrogram may be useful in the inclusion procedure for intra-articular studies
      to determine containment of the joint and also the volume that can be injected.

PMID- 16997605
TI  - [Products toxic to reproduction used in the occupational environment: Definition,
      risk assessment, classification].
AB  - European regulations (transcribed into French law) aimed at protecting employees
      from chemicals toxic to reproduction enable classification and labelling of such
      substances, if they are liable to cause an alteration of male or female
      reproductive functions or capacity, or to induce non-hereditary harmful effects
      on their offspring. Three categories can be used to classify these substances in
      two areas, namely their impairment of fertility and their effects on development.
      This classification is rarely based on epidemiological study results, but most
      often on those of experimental toxicological studies conducted by substance
      manufacturers. These reproduction toxicological studies are only compulsory above
      a certain tonnage placed on the market. The high level of this tonnage means that
      these tests are effectively only conducted on rare occasions. It is reckoned that
      there is no reproduction experimental data for over 95% of substances newly
      placed on the market. These products therefore appear to be reproduction non
      toxic only because they have not been tested. This is a major fault in the
      current labelling system, which does not allow non-toxic products to be
      differentiated from non-tested products. The future EU regulatory framework for
      Registration, Evaluation and Authorisation of CHemicals (REACH) will only
      slightly enhance information in this area. It can be estimated that over 80% of
      chemical products will not be exhaustively tested for reproduction and nearly 75%
      will not be tested to any degree.

PMID- 16997606
TI  - [Misoprostol: Why Gymiso?].

PMID- 16997607
TI  - A microcontroller system for investigating the catch effect: Functional
      electrical stimulation of the common peroneal nerve.

PMID- 16997608
TI  - Calpastatin in rat myoblasts: transient diminution and decreased phosphorylation
      depend on myogenin-directed myoblast differentiation.
AB  - The formation of skeletal muscle fibers involves cessation of myoblast division,
      followed by myoblast differentiation and fusion to multinucleated myofibers. The
      myogenic regulatory factor myogenin appears at the onset of differentiation; it
      is required for muscle fiber formation, and cannot be replaced by other factors.
      The myogenin-dependent pathways and targets are not fully known. Previous
      studies, indicating an involvement of calpain-calpastatin and caspase in myoblast
      fusion, were based on the use of various inhibitors. The availability of myogenin
      deficient cell lines that are incapable of fusion, but regain the ability to
      differentiate when transfected with myogenin, provide a convenient means to study
      calpain-calpastatin and caspase in fusing and non-fusing myoblasts without the
      use of inhibitors. The differentiating wild type myoblasts exhibit decreased
      calpastatin phosphorylation, transient diminution in calpastatin mRNA, caspase-1
      dependent diminution in calpastatin protein, and calpain-promoted proteolysis. In
      the myogenin-deficient myoblasts, calpastatin phosphorylation is not diminished,
      caspase-1 is not activated, calpastatin mRNA and protein are not diminished, and
      protein degradation does not occur. The myogenin-deficient myoblasts transfected
      with myogenin gene regain the ability to fuse, and exhibit the alterations in
      calpastatin and proteolysis observed in the wild type cells. Overall, the results
      demonstrate that the regulation of calpain in these myoblasts is independent of
      myogenin. In contrast, the regulation of calpastatin depends on myogenin
      function. The temporary diminution of calpastatin during myogenin-directed
      differentiation of myoblasts allows calpain activation and calpain-induced
      protein degradation, required for myoblast differentiation and fusion.

PMID- 16997609
TI  - Extraction of the midsagittal plane from morphological neuroimages using the
      Kullback-Leibler's measure.
AB  - A theoretically simple and computationally efficient method to extract the
      midsagittal plane (MSP) from volumetric neuroimages is presented. The method
      works in two stages (coarse and fine) and is based on calculation of the Kullback
      and Leibler's (KL) measure, which characterizes the difference between two
      distributions. Slices along the sagittal direction are analyzed with respect to a
      reference slice to determine the coarse MSP. To calculate the final MSP, a local
      search algorithm is applied. The proposed method does not need any preprocessing,
      like reformatting, skull stripping, etc. The algorithm was validated
      quantitatively on 75 MRI datasets of different pulse sequences (T1WI, T2WI, FLAIR
      and SPGR) and MRA. The angular and distance errors between the calculated MSP and
      the ground truth lines marked by the expert were calculated. The average distance
      and angular deviation were 1.25 pixels and 0.63 degrees , respectively. In
      addition, the algorithm was tested qualitatively on PD, FLAIR, MRA, and CT
      datasets. To analyze the robustness of the method against rotation, inhomogeneity
      and noise, the phantom data were used.

PMID- 16997610
TI  - What is the relationship between phonological short-term memory and speech
      processing?
AB  - Traditionally, models of speech comprehension and production do not depend on
      concepts and processes from the phonological short-term memory (pSTM) literature.
      Likewise, in working memory research, pSTM is considered to be a language
      independent system that facilitates language acquisition rather than speech
      processing per se. We discuss couplings between pSTM, speech perception and
      speech production, and we propose that pSTM arises from the cycling of
      information between two phonological buffers, one involved in speech perception
      and one in speech production. We discuss the specific role of these processes in
      speech processing, and argue that models of speech perception and production, and
      our understanding of their neural bases, will benefit from incorporating them.

PMID- 16997611
TI  - Towards a true neural stance on consciousness.
AB  - Consciousness is traditionally defined in mental or psychological terms. In
      trying to find its neural basis, introspective or behavioral observations are
      considered the gold standard, to which neural measures should be fitted. I argue
      that this poses serious problems for understanding the mind-brain relationship.
      To solve these problems, neural and behavioral measures should be put on an equal
      footing. I illustrate this by an example from visual neuroscience, in which both
      neural and behavioral arguments converge towards a coherent scientific definition
      of visual consciousness. However, to accept this definition, we need to let go of
      our intuitive or psychological notions of conscious experience and let the
      neuroscience arguments have their way. Only by moving our notion of mind towards
      that of brain can progress be made.

PMID- 16997612
TI  - Neural bases of binocular rivalry.
AB  - During binocular rivalry, conflicting monocular images compete for access to
      consciousness in a stochastic, dynamical fashion. Recent human neuroimaging and
      psychophysical studies suggest that rivalry entails competitive interactions at
      multiple neural sites, including sites that retain eye-selective information.
      Rivalry greatly suppresses activity in the ventral pathway and attenuates visual
      adaptation to form and motion; nonetheless, some information about the suppressed
      stimulus reaches higher brain areas. Although rivalry depends on low-level
      inhibitory interactions, high-level excitatory influences promoting perceptual
      grouping and selective attention can extend the local dominance of a stimulus
      over space and time. Inhibitory and excitatory circuits considered within a
      hybrid model might account for the paradoxical properties of binocular rivalry
      and provide insights into the neural bases of visual awareness itself.

PMID- 16997613
TI  - Oral and oesophageal squamous cell carcinoma--a complication or component of
      autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I).
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an
      autosomal recessive disease exceptionally common in Finland. It is associated
      with a limited T lymphocyte defect, an autoimmune response to various tissues,
      particularly endocrine glands. Most patients have chronic oral candidosis, which
      has been suggested to be carcinogenic. In Finland 92 patients have been diagnosed
      with APECED and 66 of them are alive. Our aim was to study the possible
      association of APECED with oral and oesophageal carcinoma. We evaluated the
      medical histories of all 92 patients for morbidity, causes of death, and known
      risk factors for oral cancer. We invited all current patients for a clinical
      examination of their oral mucosa. Six of the 92 had developed oral or oesophageal
      squamous cell carcinoma (SCC) by the mean age of 37 (29-44years) and four of them
      had died from it. The six represent 10% of the patients older than 25years. Five
      of the six patients had long-lasting oral candidosis. Four of the six had smoked
      regularly for 15years or more. One patient had been on immunosuppressive therapy
      for 6years following kidney transplantation when SCC in her mouth occurred. The
      partial T cell defect of APECED seems to favour the growth of Candida albicans
      and predispose to chronic mucositis and SCC. Aggressive control of oral
      candidosis and close follow-up of oral mucosa is a necessity in patients with
      APECED.

PMID- 16997614
TI  - Combined effects of soluble vascular endothelial growth factor receptor FLT-1
      gene therapy and cisplatin chemotherapy in human tongue carcinoma xenografts.
AB  - The aim of the present study was to assess the anti-tumor effect of a defective
      adenovirus that expresses soluble vascular endothelial growth factor (VEGF)
      receptor FLT-1 (AdsFLT-1) in combination with cisplatin (cis
      diamminedichloroplatinum, DDP) on human tongue carcinoma Tca8113 cell xenografts
      that had been pre-established in nude mice. In vitro, Tca8113 cells secreted
      soluble FLT-1 (sFLT-1) after infection with AdsFLT-1, and the conditioned medium
      from AdsFLT-1-treated Tca8113 cells seemed to inhibit VEGF-induced proliferation
      of human umbilical vein endothelial cells. The combined effects of sFLT-1 gene
      therapy and DDP chemotherapy was then studied in well-established Tca8113
      xenografts. The concentration of sFLT-1 in serum reached a peak 8 days after
      intratumoral injection of AdsFLT-1. In these tumors, AdsFLT-1 intratumoral
      injections had only a small effect. Interestingly, when the cells were also
      exposed to DDP chemotherapy, significantly higher (P<0.05), and possibly
      synergistic, anti-tumoral effects were observed that were highly correlated to a
      marked reduction in intratumoral vascularization and an increase in tumor-cell
      apoptosis. Together, these data emphasize the potential of combining an anti
      angiogenic gene therapy strategy with a destructive approach directed against the
      tumor cells to fight human tongue carcinoma.

PMID- 16997615
TI  - Patients experience with long-term percutaneous endoscopic gastrostomy feeding
      following primary surgery for oral and oropharyngeal cancer.
AB  - Percutaneous endoscopic gastrostomy feeding (PEG) has an important role in
      providing nutritional support in selected patients undergoing treatment for oral
      and oropharyngeal cancer. Although morbidity data have been published there is
      very little from the patient perspective. The aim of this project was to devise,
      pilot and survey a PEG specific questionnaire and relate outcomes to health
      related quality of life. A cross-sectional survey was conducted in April 2005 of
      patients who were alive and disease free and treated by primary surgery for oral
      and oropharyngeal squamous cell carcinoma between 1992 and June 2004. The survey
      comprised the University of Washington Quality of Life questionnaire and a 24
      item PEG questionnaire. Of 344 alive and disease free patients, 243 (71%)
      responded. Clinical characteristics of responders and non responders were
      similar. Mean age of responders was 65 (SD 12) and 59% were male. There were 193
      (79%) patients who never had a PEG as part of their treatment, 30 (12%) who had
      their PEG removed (median 7 months), and 20 (8%) who still had a PEG (median 34
      months). Patients with PEGs reported significant deficits in all UW-QOL domains
      compared to non-PEG or PEG-removed patients and also reported a much poorer
      quality of life. The major PEG related problems were not those of discomfort,
      leakage or blockage, but interference with family life, intimate relationships,
      social activities, and hobbies. More can be done to counsel and support patients
      with long-term PEG placement.

PMID- 16997616
TI  - Genotoxic effects of exposure to radiofrequency electromagnetic fields (RF-EMF)
      in cultured mammalian cells are not independently reproducible.
AB  - Conflicting results have been published regarding the induction of genotoxic
      effects by exposure to radiofrequency electromagnetic fields (RF-EMF). Using the
      comet assay, the micronucleus test and the chromosome aberration test with human
      fibroblasts (ES1 cells), the EU-funded "REFLEX" project (Risk Evaluation of
      Potential Environmental Hazards From Low Energy Electromagnetic Field Exposure
      Using Sensitive in vitro Methods) reported clearly positive effects for various
      exposure conditions. Because of the ongoing discussion on the biological
      significance of the effects observed, it was the aim of the present study to
      independently repeat the results using the same cells, the same equipment and the
      same exposure conditions. We therefore exposed ES1 cells to RF-EMF (1800 MHz; SAR
      2 W/kg, continuous wave with intermittent exposure) for different time periods
      and then performed the alkaline (pH>13) comet assay and the micronucleus test
      (MNT). For both tests, clearly negative results were obtained in independently
      repeated experiments. We also performed these experiments with V79 cells, a
      sensitive Chinese hamster cell line that is frequently used in genotoxicity
      testing, and also did not measure any genotoxic effect in the comet assay and the
      MNT. Appropriate measures of quality control were considered to exclude
      variations in the test performance, failure of the RF-EMF exposure or an
      evaluation bias. The reasons for the difference between the results reported by
      the REFLEX project and our experiments remain unclear.

PMID- 16997617
TI  - The activin axis in liver biology and disease.
AB  - Activins are a closely related subgroup within the TGFbeta superfamily of growth
      and differentiation factors. They consist of two disulfide-linked beta subunits.
      Four mammalian activin beta subunits termed beta(A), beta(B), beta(C), and
      beta(E), respectively, have been identified. Activin A, the homodimer of two
      beta(A) subunits, has important regulatory functions in reproductive biology,
      embryonic development, inflammation, and tissue repair. Several intra- and
      extracellular antagonists, including the activin-binding proteins follistatin and
      follistatin-related protein, serve to fine-tune activin A activity. In the liver
      there is compelling evidence that activin A is involved in the regulation of cell
      number by inhibition of hepatocyte replication and induction of apoptosis. In
      addition, activin A stimulates extracellular matrix production in hepatic
      stellate cells and tubulogenesis of sinusoidal endothelial cells, and thus
      contributes to restoration of tissue architecture during liver regeneration.
      Accumulating evidence from animal models and from patient data suggests that
      deregulation of activin A signaling contributes to pathologic conditions such as
      hepatic inflammation and fibrosis, acute liver failure, and development of liver
      cancer. Increased production of activin A was suggested to be a contributing
      factor to impaired hepatocyte regeneration in acute liver failure and to
      overproduction of extracellular matrix in liver fibrosis. Recent evidence
      suggests that escape of (pre)neoplastic hepatocytes from growth control by
      activin A through overexpression of follistatin and reduced activin production
      contributes to hepatocarcinogenesis. The role of the activin subunits beta(C) and
      beta(E), which are both highly expressed in hepatocytes, is still quite
      incompletely understood. Down-regulation in liver tumors and a growth inhibitory
      function similar to that of beta(A) has been shown for beta(E). Contradictory
      results with regard to cell proliferation have been reported for beta(C). The
      profound involvement of the activin axis in liver biology and in the pathogenesis
      of severe hepatic diseases suggests activin as potential target for therapeutic
      interventions.

PMID- 16997618
TI  - Electronic, epr and magnetic studies of Co(II), Ni(II) and Cu(II) complexes with
      thiosemicarbazone (L1) and semicarbazone (L2) derived from pyrole-2
      carboxyaldehyde.
AB  - Co(II), Ni(II) and Cu(II) complexes are synthesized with thiosemicarbazone (L(1))
      and semicarbazone (L(2)) derived from pyrole-2-carboxyaldehyde. These complexes
      are characterized by elemental analysis, molar conductance, magnetic
      susceptibility measurements, mass, IR, electronic and EPR spectral studies . The
      molar conductance measurements of the complexes in DMSO correspond to non
      electrolytic nature except Co(L1)2(NO3)2 and Ni(L1)2(NO3)2 complexes which are
      1:2 electrolytes. All the complexes are of high-spin type. On the basis of
      spectral studies an octahedral geometry may be assigned for Co(II) and Ni(II)
      complexes except Co(L1)2(NO3)2 and Ni(L1)2(NO3)2 which are of tetrahedral
      geometry. A tetragonal geometry may be suggested for Cu(II) complexes.

PMID- 16997619
TI  - Characterisation of the 1H and 13C NMR spectra of methylcitric acid.
AB  - Methylcitric acid (MCA) was synthesised in Reformatsky reaction (2RS, 3RS
      stereoisomers) and in the nucleophilic addition (2RS, 3SR stereoisomers). The
      stereoselectivity of these reactions was analysed. (1)H and (13)C NMR spectra of
      diastereoisomers of methylcitric acid were recorded and interpreted. The values
      of (1)H chemical shifts and (1)H-(1)H coupling constants were analysed. Proton
      decoupled high-resolution (13)C NMR spectra of MCA diastereoisomers were measured
      in a series of dilute water solutions of various acidities. These data may
      provide a basis for unequivocal determination of the presence of MCA in the urine
      samples of patients' suffering from propionic acidemia, methylmalonic aciduria,
      or holocarboxylase synthetase deficiency. NMR spectroscopy enables determination
      of MCA diastereoisomers in body fluids and can be a complementary and useful
      diagnostic tool.

PMID- 16997620
TI  - Technology, governance and patient safety: systems issues in technology and
      patient safety.
AB  - Technology and equipment are often identified as contributors to adverse medical
      events, however technology is seldom the focal point of investigation as a source
      of medical error or adverse event. It is often seen as both a means of reducing
      error (e.g., automated drug dispensing machines) or as a major contributing
      factor to adverse events (e.g., through cognitive overload). Here we review
      literature about the governance of technology in health settings, which is
      addressed in relation to patient safety. We outline the challenges of addressing
      technology governance issues in the health sector, provide an overview of
      governance processes, and suggest that technology related adverse events have
      been largely conceptualized as device and user problems rather than system or
      socio-technical problems, which is reflected in governance processes associated
      with medical devices. A recognition of the situatedness of medical practices
      implies that new forms of governance may be required that place greater emphasis
      on socio-technical and systems issues.

PMID- 16997621
TI  - Who is in charge of patient safety? Work practice, work processes and utopian
      views of automatic drug dispensing systems.
AB  - In June 2003, a large, Canadian tertiary care facility introduced automatic drug
      dispensing machines on all units when it opened up a new building. In this paper,
      we provide an overview of the automatic drug dispensing system (ADS)
      implementation at the hospital. Our findings, based on daily field observations
      and interviews during and after implementation, with regular follow-up visits to
      the field site illustrate how the introduction of the ADS brought to light work
      practices that sometimes compromised patient safety. We suggest that utopian
      views of automatic drug dispensing machines obfuscate the challenges inherent to
      implementing such systems, and deter stakeholders from performing rigorous
      evaluation of the costs (both social and economic) and benefits of investing in
      such systems. Our work contributes to debates about the socio-technical efficacy
      of automating medication dispensing and delivery, and suggests that the balance
      of power in the patient safety equation lies in the work context and
      implementation issues, and not just the technology. For technology
      implementations to be successful considering that technologies frequently cross
      over jurisdictional boundaries, planning and implementation have to be conducted
      at a system wide level.

PMID- 16997622
TI  - Evaluation of the role of sympathetic denervation on hepatic function.
AB  - It is acknowledged that autonomic nerves play an important role on liver
      function. Sympathetic nerve is the main component of them. This study is to
      evaluate the effects of sympathetic denervation of the liver on liver function in
      the normal and chemically injured liver, and its influence on liver regeneration.
      Eighty healthy male Wistar rats were divided randomly into four groups: Sham
      group, carbon tetrachloride group (CCL4), 6-hydroxydopamine group (6-OHDA), and
      CCL4+6-OHDA group. Chemical denervation model was made by injection of 6-OHDA
      (2ml, 100mg/l) through the mesenteric vein of jejunum loop. Acute liver injury
      model was established by using CCL4. Blood chemistry, ATP, arterial ketone body
      ratio (AKBR) and indocyanine green (ICG(15)) were measured in each group after
      administration of sympathetic denervation or/and acute liver injury. Liver
      regeneration was assessed with hepatic mass index (HMI), rate of liver
      regeneration (RLR), mitotic index (MI) and the rates of DNA synthesis under
      sympathetic denervation. Chemical denervation resulted in significant changes of
      liver function tests under acute liver injury, and had beneficial effects on
      protein anabolism, metabolism of bilirubin and energy, and ICG excretion,
      meanwhile, alleviated low potassium in serum. However, sympathetic denervation
      only had no effects on liver function tests. It decreased significantly in
      sympathetic denervation group for HMI, RLR, MI and the rate of DNA synthesis with
      3H-TdR (P<0.01). It is concluded that sympathetic denervation can alleviate liver
      injury by CCL4, impair liver regeneration, but has no effects on liver function
      tests under normal.

PMID- 16997624
TI  - Lipid requirements for endocytosis in yeast.
AB  - Endocytosis is, besides secretion, the most prominent membrane transport pathway
      in eukaryotic cells. In membrane transport, defined areas of the donor membranes
      engulf solutes of the compartment they are bordering and bud off with the aid of
      coat proteins to form vesicles. These transport vehicles are guided along
      cytoskeletal paths, often matured and, finally, fuse to the acceptor membrane
      they are targeted to. Lipids and proteins are equally important components in
      membrane transport pathways. Not only are they the structural units of membranes
      and vesicles, but both classes of molecules also participate actively in membrane
      transport processes. Whereas proteins form the cytoskeleton and vesicle coats,
      confer signals and constitute attachment points for membrane-membrane
      interaction, lipids modulate the flexibility of bilayers, carry protein
      recognition sites and confer signals themselves. Over the last decade it has been
      realized that all classes of bilayer lipids, glycerophospholipids, sphingolipids
      and sterols, actively contribute to functional membrane transport, in particular
      to endocytosis. Thus, abnormal bilayer lipid metabolism leads to endocytic
      defects of different severity. Interestingly, there seems to be a great deal of
      interdependence and interaction among lipid classes. It will be a challenge to
      characterize this plenitude of interactions and find out about their impact on
      cellular processes.

PMID- 16997623
TI  - Yeast sphingolipids: recent developments in understanding biosynthesis,
      regulation, and function.
AB  - Sphingolipids function as required membrane components of virtually all
      eukaryotic cells. Data indicate that members of the sphingolipid family of
      lipids, including sphingoid bases, sphingoid base phosphates, ceramides, and
      complex sphingolipids, serve vital functions in cell biology by both direct
      mechanisms (e.g., binding to G-protein coupled receptors to transduce an
      extracellular signal) and indirect mechanisms (e.g., facilitating correct
      intracellular protein transport). Because of the diverse roles these lipids play
      in cell biology, it is important to understand not only their biosynthetic
      pathways and regulation of sphingolipid synthesis, but also the mechanisms by
      which some sphingolipid species with specific functions are modified or converted
      to other sphingolipid species with alternate functions. Due to many factors
      including ease of culture and genetic modification, and conservation of major
      sphingolipid metabolic pathways, Saccharomyces cerevisiae has served as an ideal
      model system with which to identify enzymes of sphingolipid biosynthesis and to
      dissect sphingolipid function. Recent exciting developments in sphingolipid
      synthesis, transport, signaling, and overall biology continue to fuel vigorous
      investigation and inspire investigations in mammalian sphingolipid biology.

PMID- 16997625
TI  - Cardiac cell death in early diabetes and its modulation by dietary fatty acids.
AB  - Diabetes is a significant risk factor for cardiovascular diseases with the
      majority of these complications being attributed to coronary vascular pathology.
      However, both in humans and animal models of diabetes, an additional heart muscle
      specific disease in the absence of any vascular pathology has also been
      described. Even though diverse mechanisms have been suggested to explain the
      etiology of this diabetic heart disease, important roles of oxidative stress and
      cell death have been implicated behind this disorder. Apart from hyperglycemia,
      cardiac lipid overload is currently believed to be responsible for oxidative
      stress and cell death in the diabetic heart. Although lipotoxicity is considered
      a major player in precipitating cardiac cell death, most of the existing work
      revolves around saturated and monounsaturated fatty acids. Looking at the current
      western diet with its preponderance of omega-6 polyunsaturated fatty acids
      (PUFA), more emphasis should be placed on its role in the diabetic heart. In this
      review, we shall highlight the most intriguing and updated findings of the
      differential fatty acid classes including omega-6 PUFA and their
      established/probable roles on diabetic myocardial cell death.

PMID- 16997626
TI  - Resting state oscillatory brain dynamics in Parkinson's disease: an MEG study.
AB  - OBJECTIVE: The pathophysiological mechanisms of cognitive dysfunction and
      dementia in Parkinson's disease (PD) are still poorly understood. Altered resting
      state oscillatory brain activity may reflect underlying neuropathological
      changes. The present study using magneto encephalography (MEG) was set up to
      study differences in the pattern of resting state oscillatory brain activity in
      groups of demented and non-demented PD patients and healthy, elderly controls.
      METHODS: The pattern of MEG background oscillatory activity was studied in 13
      demented PD patients, 13 non-demented PD patients and 13 healthy controls. Whole
      head MEG recordings were obtained in the morning in an eyes closed and an eyes
      open, resting state condition. Relative spectral power was calculated using Fast
      Fourier Transformation in delta, theta, alpha, beta and gamma frequency bands.
      RESULTS: In the non-demented PD patients, relative theta power was diffusely
      increased and beta power concomitantly decreased relative to controls. gamma
      Power was decreased in central and parietal channels. In the demented PD
      patients, a diffuse increase in relative delta and to lesser extent theta power
      and a decrease in relative alpha, beta and to lesser extent gamma power were
      found in comparison to the non-demented PD group. In addition, reactivity to eye
      opening was much reduced in the demented PD group. CONCLUSIONS: Parkinson's
      disease is characterized by a slowing of resting state brain activity involving
      theta, beta and gamma frequency bands. Dementia in PD is associated with a
      further slowing of resting state brain activity, additionally involving delta and
      alpha bands, as well as a reduction in reactivity to eye-opening. SIGNIFICANCE:
      The differential patterns of slowing of resting state brain activity in demented
      and non-demented PD patients suggests that, in conjunction with a progression of
      the pathological changes already present in non-demented patients, additional
      mechanisms are involved in the development of dementia in PD.

PMID- 16997627
TI  - Interactional behaviour as a marker for screening patients with environment
      related complaints.
AB  - BACKGROUND: Adequate assessment of symptoms of patients suffering from
      environmental illnesses requires appropriate procedures such as psychological and
      psychiatric diagnostics, medical screening and a thorough analysis of noxious
      environmental factors. The Basel pilot research project established a multi
      methodological assessment procedure that meets these criteria. However, an
      exhaustive three-fold analysis is very costly in terms of both equipment and
      personnel, and hence the need for a heuristic approach and pre-screening
      persists. METHOD: The three-fold diagnostic approach was preceded by a structured
      psychodynamic interview; the findings were used to construct a new profile of the
      patient's interactional behaviour (IB) in conjunction with the interviewer's
      countertransference. The extent to which this new profile could predict the
      results of the multi-method assessment was then assessed. RESULTS: A low level of
      IB on the part of the patient significantly predicted the degree of stress and
      the extent of the psychiatric diagnosis, including personality disorders. A
      negative IB was associated with negative personality traits. Furthermore, a high
      level of IB implied more medical, but not more environmental, findings which
      could plausibly be related to the patient's complaints. CONCLUSIONS: Assessment
      of patients' IB in conjunction with one's own countertransference is very helpful
      as a preliminary heuristic approach and may lead to consequences for treatment
      and therapy. Therefore, the training provided for experts who deal with patients
      suffering from environment-related complaints should place more specific emphasis
      on assessing patients' behaviour and on incorporating information gathered from
      countertransference. Nevertheless, an interdisciplinary assessment including
      medical, psychological/psychiatric, and environmental expertise remains mandatory
      for adequate and satisfactory diagnosis of patients with environment-related
      complaints.

PMID- 16997628
TI  - Making a case for domperidone in the treatment of gastrointestinal motility
      disorders.
AB  - There are very few treatment options currently available for patients with
      gastrointestinal motility disorders, especially patients with gastroparesis.
      Domperidone, a peripheral dopamine receptor antagonist, has been successfully
      used for decades in the US and marketed in many countries for the treatment of
      gastroparesis. Its use, however, has recently become controversial owing to
      safety concerns, and it has never been approved for marketing by the FDA. During
      the 1990s, domperidone was available to US gastroenterologists under a
      compassionate-use program by Janssen Pharmaceutica, as the manufacturer worked
      towards, and fell short of, full US market approval. Medical studies, trials and
      case reports demonstrate the superior efficacy of domperidone when compared with
      placebo and other pharmaceutical therapies available. Data on the cardiac
      toxicity associated with oral use of domperidone fail to be convincing.

PMID- 16997629
TI  - Hitting HIV where it hurts: an alternative approach to HIV vaccine design.
AB  - The ability of HIV-1 to mutate represents a major challenge to current vaccine
      approaches. However, some individuals achieving control of HIV during natural
      infection seem unique in their dominant targeting by cellular immune responses of
      conserved regions of HIV that, if mutated, exact a substantial impact on viral
      replicative capacity, or fitness. Notably, the partial suppression of HIV in
      treated individuals harboring viruses with drug-resistant mutations has also been
      linked to impaired viral fitness. The convergence of these observations suggests
      that vaccines designed to focus immune responses narrowly against regions of HIV
      susceptible to highly deleterious mutations might prove effective in controlling
      viral replication to levels that slow disease progression and reduce
      transmission. Therefore, it will be crucial to identify these "Achilles heels" of
      HIV that might represent uniquely susceptible targets, and test whether vaccine
      constructs enabling specific targeting of CD8(+) T-cell responses against such
      regions would enable the control of HIV and SIV.

PMID- 16997630
TI  - Bystander T cell activation--implications for HIV infection and other diseases.
AB  - T cells are subject to tight regulatory measures, as uncontrolled responses might
      be detrimental to the host. Control measures include central or thymic tolerance,
      and peripheral tolerance mechanisms acting after naive T cells have encountered
      their cognate antigen, such as anergy induction, the contraction phase (whereby
      the majority of the expanded effector population undergoes apoptosis), and the
      action of regulatory T (Treg) cells. However, bystander T-cell activation
      circumvents the requirement for specific T-cell receptor stimulation, enabling T
      cells to bypass certain control checkpoints. The physiological relevance of the
      phenomenon is the subject of much controversy. This article argues that although
      of little consequence in the healthy individual, bystander activation could have
      a devastating impact in the context of disease. We focus on HIV and infection
      triggered autoimmune disease as examples.

PMID- 16997631
TI  - T cell memory and protective immunity by vaccination: is more better?
AB  - Protection against intracellular pathogens or tumor antigens requires T-cell
      mediated responses. Recently, it has become apparent that protection against
      disease correlates with T cells of the central memory type in many instances.
      Here, we analyze current data to distill a set of rules for the induction and
      maintenance of central memory T-cell responses. Recent studies show that T-cell
      help and the lack of overt inflammation at the time of priming are prerequisite
      for the induction, maintenance and expansion of memory T cells. Central to our
      hypothesis is that, in addition to these factors, successful vaccination in the
      immunologically inexperienced individual should be based on low antigen dose, to
      decelerate replicative senescence in responding cells and favor lineage
      differentiation of central memory T cells. In the immunologically experienced
      individual, it will be necessary, in addition, to abate the antigen load in
      plasma before vaccination. These guiding principles might help to raise improved
      protective T-cell responses by vaccination in humans.

PMID- 16997632
TI  - Lymphocyte apoptosis as an immune subversion strategy of microbial pathogens.
AB  - Apoptosis is a component of cellular death in several immunological reactions.
      Lymphocyte apoptosis is a feature of negative selection of thymic lymphocytes.
      Target cells die by apoptosis during their interaction with cytotoxic T cells.
      Antigens derived from apoptotic cells can be cross-presented by antigen
      presenting cells (APCs). In these examples, apoptotic death is a beneficial
      feature for the individual. The apoptosis of cells also occurs during infection
      with a variety of microorganisms, but this process can be detrimental to the
      handling of the infection by the host. Here, we aim to highlight some of the
      recent advances in understanding why apoptosis can be a detrimental event during
      infection. We will focus on recent research with the intracellular bacterial
      pathogen Listeria monocytogenes, which demonstrates how apoptosis is induced,
      some of the host pathways that are exploited and the immunological consequences
      of cell death. We propose that L. monocytogenes causes lymphocyte death by
      enhancing the cell-death programs of the host. The presence of apoptotic
      lymphocytes downregulates early innate immunity, creating a permissive
      environment for bacterial growth.

PMID- 16997633
TI  - Performance evaluation of arterial femoral sheath removal by registered nurses
      after PCI.
AB  - BACKGROUND: Sheath removal after PCI by registered nurses can improve patients'
      comfort and shorten immobilisation time. As sheath removal is not without risk,
      it is important to assure the quality of performance. AIMS: The aim was (a) to
      check if nurses' performance in 1999 and 2005 was in accordance with the protocol
      for arterial sheath removal and (b) to compare both measurements to explore
      differences in performance over time. METHODS: We trained registered nurses in
      sheath removal and observed them during sheath removal in elective uncomplicated
      PCI-patients. We developed and used a checklist, including 10 elements and 65
      items. RESULTS: Both in 1999 (n=43 observations with 13 nurses) and 2005 (n=42
      observations with 16 nurses) the norm of more than 90% for the total score was
      not achieved: we found 82% and 80%, respectively. Four elements scored more than
      90%, and three elements scored less than 80% at both points in time. The results
      on the other three elements differed significantly over time. CONCLUSION:
      Registered nurses achieved the norm for good performance (80-89%) of removing
      arterial sheaths according to protocol after a training programme and this is
      stable in time. Since the norm for excellent performance (> or =90%) was not
      achieved, current performance could be improved, e.g. by yearly repetition of
      training and observation of skills. More research is needed, and could focus on
      the validation of the instrument. Also multi-centre studies with this checklist
      could test the association between the quality of arterial femoral sheath removal
      and the occurrence of vascular complications.

PMID- 16997634
TI  - Manageability, vulnerability and interaction: a qualitative analysis of acute
      myocardial infarction patients' conceptions of the event.
AB  - BACKGROUND: Delay in seeking care remains a problem for many patients with
      myocardial infarction. There is a great deal of knowledge available about
      clinical factors contributing to this delay, while studies focusing on the
      patients' own experiences are few. AIM: Describe variations in how individuals
      perceived suffering symptoms of an acute myocardial infarction. DESIGN: A
      qualitative method using phenomenographic design was applied. Interviews were
      conducted with 15 strategically selected patients with myocardial infarction.
      FINDINGS: Eight sub-categories in the pre-hospital phase were summarised into
      three categories: manageability, vulnerability, and interaction. To manage their
      situation, patients expressed a need to understand it and to have a similar
      situation to compare with. They also described coping with the arising threat to
      their lives by self-medication or denying their symptoms. Patients expressed
      vulnerability, with feelings of anxiety, both as triggers and barriers to seeking
      medical care. In interaction with others, psychosocial support and guidance from
      the environment, was fundamental in helping the patients to manage the situation.
      CONCLUSIONS: There were large variations in myocardial infarction patients'
      conceptions of the event. To improve disease management in the pre-hospital
      phase, the awareness of this large variation in conceptions about suffering
      symptoms of an myocardial infarction could be used in the dialogue between
      patients and health care professionals, in cardiac prevention programmes, as well
      as in health care education.

PMID- 16997635
TI  - Fear sensitivity and the psychological profile of patients with psychogenic
      nonepileptic seizures.
AB  - Psychogenic nonepileptic seizures (PNES) remain a poorly understood phenomenon
      for both patients and their physicians. Recent work has begun to focus on the
      possible psychological underpinnings of this diagnosis, but few studies have
      focused on specific emotional pathologies. This study sought to investigate the
      impact of a specific emotional measure: self-reported fear sensitivity. Three
      patient groups (patients with PNES, patients with epilepsy, and healthy
      volunteers) were administered the Modified Fear Survey Schedule, along with other
      neuropsychological batteries. As expected, the PNES and epilepsy cohorts
      demonstrated elevated levels of depression, anxiety, and comorbid psychiatric
      conditions. The PNES group independently exhibited a statistically significant
      higher level of fear sensitivity compared with both patients with epilepsy and
      healthy volunteers. This fear-specific trait was independent of other comorbid
      psychological factors or psychiatric conditions. These results suggest that
      patients with PNES exhibit disproportionately elevated fear sensitivity on self
      report measures when compared with patients with epilepsy. This finding may
      reflect an elevated internal "setpoint" for appraising the intensity of emotional
      settings.

PMID- 16997636
TI  - Assessing physicians' use of treatment algorithms: Project IMPACTS study design
      and rationale.
AB  - Effective treatments for major depressive disorder have been available for 35
      years, yet inadequate pharmacotherapy continues to be widespread leading to
      suboptimal outcomes. Evidence-based medication algorithms have the potential to
      bring much-needed improvement in effectiveness of antidepressant treatment in
      "real-world" clinical settings. Project IMPACTS (Implementation of Algorithms
      using Computerized Treatment Systems) addresses the critical question of how best
      to facilitate integration of depression treatment algorithms into routine care.
      It tests an algorithm implemented through a computerized decision support system
      using a measurement-based care approach for depression against a paper-and-pencil
      version of the same algorithm and non-algorithm-based, specialist-delivered usual
      care. This paper reviews issues related to the Project IMPACTS study rationale,
      design, and procedures. Patient outcomes include symptom severity, social and
      work function, and quality of life. The economic impact of treatment is assessed
      in terms of health care utilization and cost. Data collected on physician
      behavior include degree of adherence to guidelines and physician attitudes about
      the perceived utility, ease of use, and self-reported effect of the use of
      algorithms on workload. Novel features of the design include a two-tiered study
      enrollment procedure, which initially enroll physicians as subjects, and then
      following recruitment of physicians, enrollment of subjects takes place based
      initially on an independent assessment by study staff to determine study
      eligibility. The study utilizes brief, easy-to-use symptom severity measures that
      facilitate physician decision making, and it employs a validated, phone-based,
      follow-up assessment protocol in order to minimize missing data, a problem common
      in public sector and longitudinal mental health studies. IMPACTS will assess the
      success of algorithm implementation and subsequent physician adherence using
      study-developed criteria and related statistical approaches. These new procedures
      and data points will also allow a more refined assessment of algorithm-driven
      treatment in the future.

PMID- 16997637
TI  - Cloning of hif-1alpha and hif-2alpha and mRNA expression pattern during
      development in zebrafish.
AB  - Hypoxia-inducible factors (HIFs) regulate gene expression in response to hypoxia
      and in vertebrates they are known to participate in several developmental
      processes, including angiogenesis, vasculogenesis, heart and central nervous
      system development. Over the last decade, major progress in unraveling the
      molecular mechanisms that mediate regulation of HIF proteins by oxygen tension
      has been reported, but our knowledge on their developmental regulation during
      embryogenesis in model organisms is limited. Expression of hif-1alpha and hif
      2alpha genes has been characterized during normal mouse development and they were
      found to be expressed from stages E7.5, later in E9.5 and E15.5 in several
      different tissues such as the brain, heart and blood vessels. However, there is
      no detailed temporal information on their expression at other embryonic stages,
      even though orthologous genes have been described in several different vertebrate
      species. In this study, we describe the cloning and detailed expression pattern
      of zebrafish hif-1alpha and hif-2alpha genes. Sequence analysis revealed that
      zebrafish Hif proteins are highly homologous to other vertebrate orthologues.
      Zebrafish hif-1alpha and hif-2alpha are both expressed throughout development in
      discrete territories in a dynamic pattern. Interestingly, in the notochord the
      expression of hif-1alpha is switched off, while hif-2alpha transcription is
      turned on, signifying that the two genes might have partially overlapping,
      although non-redundant functions in development. This is the first time that a
      detailed comparison of the expression of hif-1alpha and hif-2alpha is directly
      assessed in a vertebrate model system throughout development.

PMID- 16997638
TI  - Investigations in subjects with cough following upper respiratory tract
      infection.
AB  - The study aimed to investigate subjects with cough following acute upper
      respiratory tract infection (URTI), and to compare those subjects unable to
      suppress cough ("non-suppressors") with those who were able to suppress cough
      ("suppressors"). Forty-three URTI subjects participated, 31 with cough associated
      with acute URTI and 12 healthy controls; 21 of the coughing subjects were
      "suppressors", 10 were "non-suppressors". We obtained responses to chemical and
      mechanical stimulation of the nasal cavity or the pharynx using both
      psychophysical measures and event-related potentials. The study provided the
      following results: (1) "non-suppressors" did not exhibit significantly different
      intensity ratings or event-related potentials in comparison to "suppressors" in
      terms of responses to intranasal irritant, mechanical, or olfactory stimuli; (2)
      when pharyngeal mechanical stimuli were investigated "suppressors" rated the
      stimuli as more intense than "non-suppressors" and controls; (3) latencies of
      event-related potentials to pharyngeal stimuli were longest in "non-suppressors".
      Keeping in mind the relatively small sample size, it appears possible to
      differentiate certain types of cough during uncomplicated URTI. This may help to
      explain interindividual differences in responsiveness to cough medication.

PMID- 16997639
TI  - Purification and characterization of a low molecular weight multifunctional
      cytotoxic phospholipase A2 from Russell's viper venom.
AB  - A basic toxin from Russell's viper venom of 7.2 kDa (RVV-7) has been purified to
      homogeneity after partial unfolding by 4 M urea followed by filtration through
      Centricon-30 membrane. Its N-terminal sequence showed strong homology with snake
      venom cytotoxins. Cytotoxic activity of RVV-7 has been demonstrated with B16F10
      melanoma cells. PLA2 activity was observed in cytotoxin (CX3) from Naja kauthia
      bearing sequence homology with RVV-7. Phospholipase A2 and trypsin inhibitory
      activities were also observed with RVV-7. Chemical modification and inhibition
      studies suggested independent functional sites for these activities. A
      qualitative assessment of tumor growth inhibition by RVV-7 has been made.

PMID- 16997641
TI  - Fluorescence contributions of the individual Trp residues in goat alpha
      lactalbumin.
AB  - Goat alpha-lactalbumin (GLA) contains four tryptophan (Trp) residues. In order to
      obtain information on the fluorescence contribution of the individual Trp
      residues in native GLA, we recorded the fluorescence spectra of four GLA mutants,
      W26F, W60F, W104F, and W118F, in each of which a single Trp residue was replaced
      with phenylalanine (Phe). Comparison of the fluorescence spectra of the four
      mutants with that of wild-type GLA indicated that, in native GLA, three Trp
      residues (Trp60, Trp104, and Trp118) are strongly quenched and account for the
      partial indirect quenching of Trp26. As a consequence, the fluorescence of wild
      type GLA and of the mutants W60F, W104F, and W118F mainly results from Trp26. An
      inspection of the crystal structure indicated that, in addition to the disulfide
      bonds that are in direct contact with the indole groups of Trp60 and Trp118,
      backbone peptide bonds that are in direct contact with the indole groups of
      Trp60, Trp104, and Trp118, contribute to the direct quenching effects.
      Interestingly, the lack of direct quenching of Trp26 explains why the cleavage of
      disulfide bonds by UV light is mediated more by the highly fluorescent Trp26 than
      by the less fluorescent Trp104 and Trp118.

PMID- 16997640
TI  - Simultaneous determination of 8 HIV protease inhibitors in human plasma by
      isocratic high-performance liquid chromatography with combined use of UV and
      fluorescence detection: amprenavir, indinavir, atazanavir, ritonavir, lopinavir,
      saquinavir, nelfinavir and M8-nelfinavir metabolite.
AB  - A simple, accurate and fast method was developed for determination of the
      commonly used HIV protease inhibitors (PIs) amprenavir, indinavir, atazanavir,
      ritonavir, lopinavir, nelfinavir, M8-nelfinavir metabolite and saquinavir in
      human plasma. Liquid-liquid extraction was used with hexane/ethylacetate from
      buffered plasma samples with a borate buffer pH 9.0. Isocratic chromatographic
      separation of all components was performed on an Allsphere hexyl HPLC column with
      combined UV and fluorescence detection. Calibration curves were constructed in
      the range of 0.025-10 mg/l. Accuracy and precision of the standards were all
      below 15% and the lowest limit of quantitation was 0.025 mg/l. Stability of
      quality control samples at different temperature conditions was found to be below
      20% of nominal values. The advantages of this method are: (1) inclusion and
      determination of the newly approved atazanavir, (2) simultaneous isocratic HPLC
      separation of all compounds and (3) increased specificity and sensitivity for
      amprenavir by using fluorescence detection. This method can be used for
      therapeutic drug monitoring of all PIs currently commercialised and is now part
      of current clinical practice.

PMID- 16997642
TI  - Biomechanical effects of titanium implants with full arch bridge rehabilitation
      on a synthetic model of the human jaw.
AB  - A composite model of the mandible, constituted by an inner polymeric core and a
      glass fibre reinforced outer shell, has been developed and equipped with six ITI
      titanium implants and a full gold alloy arch bridge prosthesis. The effects of
      this oral rehabilitation on the biomechanics of the mandible are investigated
      through a simulation of the lateral component of the pterygoid muscles. These
      muscles are involved as the mouth is opened and closed, hence their activity is
      very frequent. An increase of the mandible stiffness due to the prosthesis is
      observed; moreover, the coupling of the relatively stiff rehabilitation devices
      with the natural tissue analogue leads to stress-shielding and stress
      concentration in the incisal and molar regions, respectively. Although the
      amplitude of the force generated by pterygoid muscles is quite small, high
      strains over the incisal region are measured. A stress-shielding effect, of about
      20%, is observed at the symphysis as the full arch bridge prosthesis is fixed on
      the implants. Therefore, the presence of the prosthesis leads to significant
      modification of the stress field experienced by the mandible, and this may be
      relevant in relation to the biomechanics of mandibular bone remodelling.

PMID- 16997643
TI  - Migration and health: a complex relation.

PMID- 16997644
TI  - Scaling up the global health conversation.

PMID- 16997645
TI  - Eradicating polio: the final hurdles.

PMID- 16997646
TI  - A new global commitment to child survival.

PMID- 16997647
TI  - Our children: the key to our common future.

PMID- 16997648
TI  - Achieving millennium development goal 4.

PMID- 16997649
TI  - Pneumonia: the leading killer of children.

PMID- 16997650
TI  - Reducing measles mortality, reducing child mortality.

PMID- 16997651
TI  - Sustaining vitamin A supplementation requires a new vision.

PMID- 16997652
TI  - Ann Veneman: getting UNICEF back to basics.

PMID- 16997653
TI  - (The Lancet)red: a missed opportunity.

PMID- 16997654
TI  - Exceptional responses or TRIPS over red tape?

PMID- 16997655
TI  - Non-sterile injections, contaminated blood, and the spread of HIV.

PMID- 16997656
TI  - Public health approach to HIV treatment in resource-poor settings.

PMID- 16997657
TI  - Neonatal respiratory distress after antenatal corticosteroids.

PMID- 16997658
TI  - Antiretrovirals for employees of large companies in Cambodia.

PMID- 16997659
TI  - Opiate substitution treatment in the former Soviet Union.

PMID- 16997661
TI  - Countdown to 2015: tracking intervention coverage for child survival.
AB  - BACKGROUND: The fourth Millennium Development Goal (MDG) calls for a two-thirds'
      reduction between 1990 and 2015 in deaths of children younger than five years;
      achieving this will require widespread use of effective interventions, especially
      in poor countries. We present the first report of the Child Survival Countdown, a
      worldwide effort to monitor coverage of key child-survival interventions in 60
      countries with the world's highest numbers or rates of child mortality. METHODS:
      In 2005, we developed a profile for each of the 60 countries to summarise
      information on coverage with essential child survival interventions. The profiles
      also present information on demographics, nutritional status, major causes of
      death in children under 5 years of age, and the status of selected health
      policies. Progress toward the fourth MDG is summarised by comparing the average
      annual rate of reduction in under-5 mortality in each country with that needed to
      achieve the goal. The profiles also include a comparison of the proportions of
      children in the poorest and richest quintiles of the population who received six
      or more essential prevention interventions. Each country's progress (as measured
      by defined indicators of intervention coverage) was put into one of three groups
      created on the basis of international targets: "on track"; "watch and act"; and
      "high alert". For indicators without targets, arbitrary thresholds for high,
      middle, and low performance across the 60 countries were used as a basis for
      categorisation. FINDINGS: Only seven countries are on track to met MDG-4, 39
      countries are making some progress, although they need to accelerate the speed,
      and 14 countries are cause for serious concern. Coverage of the key child
      survival interventions remains critically low, although some countries have made
      substantial improvements in increasing the proportion of mothers and children
      with access to life saving interventions by as much as ten percentage points in 2
      years. Children from the poorest families were less likely than those from
      wealthier families to have received at least six essential prevention
      interventions. INTERPRETATION: Our results show that tremendous efforts are
      urgently needed to achieve the MDG for child survival. Profiles for each country
      show where efforts need to be intensified, and highlight the extent to which
      prevention interventions are being delivered equitably and reaching poor
      families. This first report also shows country-specific improvements in coverage
      and highlights missed opportunities. The "Countdown to 2015" will report on
      progress every 2 years as a strategy for increasing accountability worldwide for
      progress in child survival.

PMID- 16997662
TI  - Countdown to 2015: tracking donor assistance to maternal, newborn, and child
      health.
AB  - BACKGROUND: Timely reliable data on aid flows to maternal, newborn, and child
      health are essential for assessing the adequacy of current levels of funding, and
      to promote accountability among donors for attainment of the Millennium
      Development Goals (MDGs) for child and maternal health. We provide global
      estimates of official development assistance (ODA) to maternal, newborn, and
      child health in 2003 and 2004, drawing on data reported by high-income donor
      countries and aid agencies to the Organisation for Economic Development and
      Cooperation. METHODS: ODA was tracked on a project-by-project basis to 150
      developing countries. We applied a standard definition of maternal, newborn, and
      child health across donors, and included not only funds specific to these areas,
      but also integrated health funds and disease-specific funds allocated on a
      proportional distribution basis, using appropriate factors. FINDINGS: Donor
      spending on activities related to maternal, newborn, and child health was
      estimated to be US1990 million dollars in 2004, representing just 2% of gross aid
      disbursements to developing countries. The 60 priority low-income countries that
      account for most child and newborn deaths received 1363 million dollars, or 3.1
      dollars per child. Across recipient countries, there is a positive association
      between mortality and ODA per head, although at any given rate of mortality for
      children aged younger than 5 years or maternal mortality, there is significant
      variation in the amount of ODA per person received by developing countries.
      INTERPRETATION: The current level of ODA to maternal, newborn, and child health
      is inadequate to provide more than a small portion of the total resources needed
      to reach the MDGs for child and maternal health. If commitments are to be
      honoured, global aid flows will need to increase sharply during the next 5 years.
      The challenge will be to ensure a sufficient share of these new funds is
      channelled effectively towards the scaling up of key maternal, newborn, and child
      health interventions in high priority countries.

PMID- 16997663
TI  - Effect of the Global Alliance for Vaccines and Immunisation on diphtheria,
      tetanus, and pertussis vaccine coverage: an independent assessment.
AB  - BACKGROUND: The Global Alliance for Vaccines and Immunisation (GAVI) was created
      in 1999 to enable even the poorest countries to provide vaccines to all children.
      We aimed to assess the effect of GAVI on combined diphtheria, tetanus, and
      pertussis vaccine (DTP3) coverage. METHODS: We examined the relation between DTP3
      coverage for GAVI recipient countries from 1995 to 2004 and immunisation services
      support (ISS) and non-ISS expenditure per surviving child, controlling for income
      per head and local political governance variables. We analysed DTP3 coverage
      reported by governments and estimated by WHO/UNICEF. We also investigated the
      effect of GAVI on country reporting behaviour. RESULTS: In countries with DTP3
      coverage of 65% or less at baseline, ISS spending per surviving child had a
      significant positive effect on DTP3 coverage (p=0.0005). This effect was not
      present in countries with DTP3 coverage of 65-80% or 80% or more at baseline. If
      ISS expenditure only is assessed, the estimated cost per additional child
      immunised in countries with baseline coverage of 65% or less is US$14 and if ISS
      and non-ISS expenditures are included the cost per child is almost $20.
      INTERPRETATION: The success of ISS funding in countries with baseline DTP3
      coverage of 65% or less provides evidence that a public-private partnership can
      work to reverse a negative trend in global health and that performance-related
      disbursement can work in some settings. Because ISS funding seems to have no
      effect in countries with baseline coverage greater than 65%, GAVI should consider
      redistributing its resources to countries with the lowest coverage.

PMID- 16997665
TI  - Human schistosomiasis.
AB  - Schistosomiasis or bilharzia is a tropical disease caused by worms of the genus
      Schistosoma. The transmission cycle requires contamination of surface water by
      excreta, specific freshwater snails as intermediate hosts, and human water
      contact. The main disease-causing species are S haematobium, S mansoni, and S
      japonicum. According to WHO, 200 million people are infected worldwide, leading
      to the loss of 1.53 million disability-adjusted life years, although these
      figures need revision. Schistosomiasis is characterised by focal epidemiology and
      overdispersed population distribution, with higher infection rates in children
      than in adults. Complex immune mechanisms lead to the slow acquisition of immune
      resistance, though innate factors also play a part. Acute schistosomiasis, a
      feverish syndrome, is mostly seen in travellers after primary infection. Chronic
      schistosomal disease affects mainly individuals with long-standing infections in
      poor rural areas. Immunopathological reactions against schistosome eggs trapped
      in the tissues lead to inflammatory and obstructive disease in the urinary system
      (S haematobium) or intestinal disease, hepatosplenic inflammation, and liver
      fibrosis (S mansoni, S japonicum). The diagnostic standard is microscopic
      demonstration of eggs in the excreta. Praziquantel is the drug treatment of
      choice. Vaccines are not yet available. Great advances have been made in the
      control of the disease through population-based chemotherapy but these required
      political commitment and strong health systems.

PMID- 16997664
TI  - Effect of rosiglitazone on the frequency of diabetes in patients with impaired
      glucose tolerance or impaired fasting glucose: a randomised controlled trial.
AB  - BACKGROUND: Rosiglitazone is a thiazolidinedione that reduces insulin resistance
      and might preserve insulin secretion. The aim of this study was to assess
      prospectively the drug's ability to prevent type 2 diabetes in individuals at
      high risk of developing the condition. METHODS: 5269 adults aged 30 years or more
      with impaired fasting glucose or impaired glucose tolerance, or both, and no
      previous cardiovascular disease were recruited from 191 sites in 21 countries and
      randomly assigned to receive rosiglitazone (8 mg daily; n=2365) or placebo (2634)
      and followed for a median of 3 years. The primary outcome was a composite of
      incident diabetes or death. Analyses were done by intention to treat. This trial
      is registered at ClinicalTrials.gov, number NCT00095654. FINDINGS: At the end of
      study, 59 individuals had dropped out from the rosiglitazone group and 46 from
      the placebo group. 306 (11.6%) individuals given rosiglitazone and 686 (26.0%)
      given placebo developed the composite primary outcome (hazard ratio 0.40, 95% CI
      0.35-0.46; p<0.0001); 1330 (50.5%) individuals in the rosiglitazone group and 798
      (30.3%) in the placebo group became normoglycaemic (1.71, 1.57-1.87; p<0.0001).
      Cardiovascular event rates were much the same in both groups, although 14 (0.5%)
      participants in the rosiglitazone group and two (0.1%) in the placebo group
      developed heart failure (p=0.01). INTERPRETATION: Rosiglitazone at 8 mg daily for
      3 years substantially reduces incident type 2 diabetes and increases the
      likelihood of regression to normoglycaemia in adults with impaired fasting
      glucose or impaired glucose tolerance, or both.

PMID- 16997666
TI  - Working together to rebuild health care in post-conflict Somaliland.
AB  - In 1991, the Somali National Movement fighters recaptured the Somaliland capital
      city of Hargeisa after a 3-year civil war. The government troops of the dictator
      General Mohamed Siad Barre fled south, plunging most of Somalia into a state of
      anarchy that persists to this day. In the north of the region, the redeclaration
      of independence of Somaliland took place on May 18, 1991. Despite some sporadic
      civil unrest between 1994 and 1996, and a few tragic killings of members of the
      international community, the country has enjoyed peace and stability and has an
      impressive development record. However, Somaliland continues to await
      international recognition. The civil war resulted in the destruction of most of
      Somaliland's health-care facilities, compounded by mass migration or death of
      trained health personnel. Access to good, affordable health care for the average
      Somali remains greatly compromised. A former medical director of the general
      hospital of Hargeisa, Abdirahman Ahmed Mohamed, suggested the idea of a link
      between King's College Hospital in London, UK, and Somaliland. With support from
      two British colleagues, a fact-finding trip sponsored by the Tropical Health and
      Education Trust (THET) took place in July, 2000, followed by a needs assessment
      by a THET programme coordinator. Here, we describe the challenges of health-care
      reconstruction in Somaliland and the evolving role of the partnership between
      King's College Hospital, THET, and Somaliland within the context of the growing
      movement to link UK NHS trusts and teaching institutions with counterparts in
      developing countries.

PMID- 16997667
TI  - Limb swelling with hypereosinophilia.

PMID- 16997668
TI  - The impact of trauma activations on the care of emergency department patients
      with potential acute coronary syndromes.
AB  - STUDY OBJECTIVE: Trauma systems improve the care of trauma patients; however, it
      is possible that prioritizing the emergency care of trauma patients might
      adversely affect other potentially ill patients requiring the same resources. We
      seek to determine whether the presence of a concurrent trauma activation
      negatively affects processes of care and outcomes for patients with potential
      acute coronary syndromes. METHODS: Patients who presented to the emergency
      department (ED) with a potential acute coronary syndrome from July 2003 to June
      2004 were stratified according to whether they presented concurrently with a
      trauma activation. Structured data collection included demographics, medical
      history, and daily tracking of inhospital course. Thirty-day follow-up was
      performed. The main outcome was a composite of inhospital cardiovascular
      complications and 30-day death and myocardial infarction. Secondary outcomes were
      time from triage to ECG acquisition, transfer to an evaluation room, return of
      laboratory results, disposition decision, and actual disposition. RESULTS:
      Patients who presented concurrently with (n=357) or not concurrently with
      (n=1,235) a trauma activation were similar with respect to demographic
      characteristics, cardiac risk factors, and TIMI risk score. The unadjusted
      incidence of 30-day adverse cardiovascular events between potential acute
      coronary syndrome patients who presented with and without a concurrent trauma
      activation was 6.2% versus 3.6% (unadjusted odds ratio 1.74 [95% confidence
      interval (CI) 1.03 to 2.93]). After adjustment for measures of patient acuity
      (triage classification, TIMI risk score) and ED volume (total patient care hours
      and ED activity), concurrent trauma activation was independently associated with
      increased rate of 30-day cardiovascular complications (odds ratio 1.72; 95% CI
      1.01 to 2.92). CONCLUSION: The presence of a concurrent trauma activation at the
      time of presentation of a patient with potential acute coronary syndrome was
      associated with an increased incidence of 30-day adverse cardiovascular events.
      Although trauma activations improve the care of trauma patients, they may be
      associated with a negative impact on the care of other patients requiring
      contemporaneous resources.

PMID- 16997669
TI  - Images in emergency medicine. Emphysematous pyelonephritis.

PMID- 16997670
TI  - Heart bone connected to the... trauma bone?

PMID- 16997672
TI  - Clinical policy: indications for reperfusion therapy in emergency department
      patients with suspected acute myocardial infarction. American College of
      Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on
      Reperfusion Therapy in Emergency Department Patients with Suspected Acute
      Myocardial Infarction.

PMID- 16997673
TI  - Annual bed statistics give a misleading picture of hospital surge capacity.
AB  - STUDY OBJECTIVE: I describe how annual hospital surge capacity is affected by
      within-year variation in patient volume and bed supply. METHODS: Surge capacity
      was measured as the percentage and total number of hospital beds that are not
      occupied by patients. Administrative data were used to calculate these bed
      statistics for 78 hospitals in New Jersey--statewide and by emergency planning
      regions--in 2003. Annual bed statistics were compared to more refined
      calculations for each day of the year. Calculated numbers of empty beds were
      compared to federal disaster planning benchmarks. RESULTS: Annual bed statistics
      showed no major limitations on surge capacity. Statewide occupancy rates were
      well below 80% (ie, more than 20% of beds were empty), and the number of empty
      beds that were set up and staffed (ie, maintained) was well above federal
      disaster planning benchmarks. In contrast, daily bed statistics reveal long
      periods in 2003 when regional and statewide surge capacity was severely strained.
      Strained capacity was most likely to occur on Tuesdays through Fridays and least
      likely to occur on weekends. On 212 days, statewide occupancy of maintained beds
      met or exceeded 85%. This occupancy rate met or exceeded 90% and 95% on 88 and 4
      days, respectively. On 288 days, the statewide number of empty maintained beds
      fell below the federal planning benchmark. CONCLUSION: Annual bed statistics give
      a misleading picture of hospital surge capacity. Analysis of surge capacity
      should account for daily variation in patient volume and within-year variation in
      bed supply.

PMID- 16997674
TI  - Hospital surge capacity: if you can't always get what you want, can you get what
      you need?

PMID- 16997675
TI  - Modified N95 mask delivers high inspired oxygen concentrations while effectively
      filtering aerosolized microparticles.
AB  - STUDY OBJECTIVE: In a pandemic, hypoxic patients will require an effective oxygen
      (O2) delivery mask that protects them from inhaling aerosolized particles
      produced by others, as well as protecting the health care provider from exposure
      from the patient. We modified an existing N95 mask to optimize O2 supplementation
      while maintaining respiratory isolation. METHODS: An N95 mask was modified to
      deliver O2 by inserting a plastic manifold consisting of a 1-way inspiratory
      valve, an O2 inlet and a gas reservoir. In a prospective repeated-measures study,
      we studied 10 healthy volunteers in each of 3 phases, investigating (1) the
      fractional inspiratory concentrations of O2 (F(I)O2) delivered by the N95 O2
      mask, the Hi-Ox80 O2 mask, and the nonrebreathing mask during resting ventilation
      and hyperventilation, each at 3 O2 flow rates; (2) the ability of the N95 mask,
      the N95 O2 mask, and the nonrebreathing mask to filter microparticles from
      ambient air; and (3) to contain microparticles generated inside the mask.
      RESULTS: The F(I)O2s (median [range]) delivered by the Hi-Ox80 O2 mask, the N95
      O2 mask, and the nonrebreathing mask during resting ventilation, at 8 L/minute O2
      flow, were 0.90 (0.79 to 0.96), 0.68 (0.60 to 0.85), and 0.59 (0.52 to 0.68),
      respectively. During hyperventilation, the FiO2s of all 3 masks were clinically
      equivalent. The N95 O2 mask, but not the nonrebreathing mask, provided the same
      efficiency of filtration of internal and external particles as the original N95,
      regardless of O2 flow into the mask. CONCLUSION: An N95 mask can be modified to
      administer a clinically equivalent FiO2 to a nonrebreathing mask while
      maintaining its filtration and isolation capabilities.

PMID- 16997676
TI  - "Should I give you my smoking lecture now or later?" Characterizing emergency
      physician smoking discussions and cessation counseling.
AB  - STUDY OBJECTIVE: We determine frequency and manner in which emergency physicians
      address smoking with their patients. METHODS: This was a descriptive secondary
      analysis of 871 audiotapes of physician-patient interactions collected during a
      trial assessing the effect of computer-based health risk assessment on emergency
      physician-patient communication. Consenting nonemergency female patients, ages 18
      to 65 years, were enrolled from 2 socioeconomically diverse academic emergency
      department (EDs) for audiotaping of the ED visit. All audio files with any
      mention of smoking were independently coded with an in-depth structured coding
      form to characterize the nature of smoking-related discussions. Logistic
      regression was used to determine factors associated with emergency physician
      screening and discussion of tobacco exposure with women patients. RESULTS:
      Overall, 484 of 871 (56%) participants were verbally screened for smoking, with
      156 of 484 (32%) disclosing current smoking, with similar incidence at both
      sites. Tobacco screening was higher (odds ratio 2.2; 95% confidence interval 1.3
      to 3.5), whereas rates of smoking-related discussions were lower (odds ratio
      0.41; 95% confidence interval 0.17 to 0.98) at the urban site. At both sites,
      physicians tended to screen and discuss smoking when patients presented with a
      health condition that could be aggravated by smoking. Only 56% of discussions
      with current smokers contained advice to quit, 16% included assessment of
      readiness to quit, and a minority (13%) included a referral. Physician
      empathy/encouragement was associated with patients' detailing quit attempts.
      CONCLUSION: Emergency physicians were likely to gather information about smoking
      but not to counsel or advise patients to quit. These results raise the question
      of whether emergency medicine resident training should include additional
      emphasis on smoking cessation counseling and motivational interviewing
      techniques.

PMID- 16997677
TI  - Should emergency physicians help smokers quit?

PMID- 16997678
TI  - Tobacco control interventions in the emergency department: a joint statement of
      emergency medicine organizations.
AB  - Smoking is the leading cause of preventable death and illness in the United
      States. National practice guidelines call for all health care providers to "ask"
      all patients about tobacco use, and to "advise, assess, assist, arrange" when
      smokers want to quit smoking (the "5 As"). Emergency departments (EDs) have not
      been an important locus of tobacco control efforts, although ED patients
      typically smoke at rates exceeding that of the general population, are interested
      in quitting, and often have limited access to primary care. To address the role
      of emergency medicine in tobacco control, the American College of Emergency
      Physicians convened a task force of representatives of major emergency medicine
      professional organizations. Funded by the Robert Wood Johnson Foundation, the
      group met in 2004 and 2005. This article represents a summary of the task force's
      recommendations for tobacco control practice, training, and research. We call on
      emergency care providers to routinely assess patients' smoking status, offer
      brief advice to quit, and refer patients to the national smokers' Quitline (800
      QUIT-NOW) or a locally available program. Given the global burden of tobacco
      related illness, the task force considers it essential for emergency physicians
      to conduct research into the efficacy of ED-based interventions and to place
      tobacco control into the training curriculum for emergency medicine residencies.
      Tobacco control fits within the traditions of other ED-based public health
      practices, such as injury control. ED-based tobacco control would allow the
      specialty to help fulfill the Healthy People 2010 mandate to reduce the
      prevalence of smoking among US citizens.

PMID- 16997679
TI  - Approaches to patient health information exchange and their impact on emergency
      medicine.
AB  - Regional health information organizations and electronic health information
      exchange may have an important impact on the practice of emergency medicine in
      the United States. Regional health information organizations are local or
      regional information-sharing networks that enable electronic data interchange
      among stakeholders in a given geographic area. These stakeholders may include
      hospitals, skilled nursing facilities, clinics, private physicians' offices,
      pharmacies, laboratories, radiology facilities, health departments, payers, and
      possibly the patients themselves. Regional health information organizations are
      being formed across the country to improve the safety and efficiency of clinical
      care; improve public health efforts, biosurveillance, and disaster management
      response; and potentially create large databases of deidentified aggregate data
      for research. Because of the unique need for rapid access to information and the
      acuity of the clinical environment, few areas of the health care delivery system
      stand to change and benefit more from health information exchange than our
      nation's emergency departments. This article will explain the motivation for the
      development of regional health information organizations, identify some of the
      important issues in their formation, and discuss how their development might
      affect the practice of emergency medicine.

PMID- 16997680
TI  - Etomidate versus midazolam for procedural sedation in pediatric outpatients: a
      randomized controlled trial.
AB  - STUDY OBJECTIVE: Midazolam is widely used for procedural sedation and analgesia.
      Etomidate has been studied mostly in adults. Our objective is to compare the
      efficacy of etomidate and midazolam for achieving procedural sedation and
      analgesia in children. METHODS: A randomized, double-blind, emergency department
      and orthopedic clinic-based trial was carried out among patients aged 2 to 18
      years with displaced extremity fractures. Patients were administered 1 microg/kg
      of fentanyl and either 0.2 mg/kg of etomidate or 0.1 mg/kg of midazolam. Adequate
      sedation was defined, for the purpose of this study, as a score of 4 or more on
      the Ramsay Sedation Scale. The primary outcome was induction and recovery time.
      The rates of adverse events, success of fracture reduction, and parent and
      physician satisfaction were also compared. RESULTS: From April to August 2004,
      100 of 128 eligible patients were enrolled (age 8.7+/-3.7 years; 50% male
      patients). A higher proportion of patients attained adequate sedation among those
      who received etomidate: 46 of 50 (92%) versus 18 of 50 (36%) (delta 56%; 95%
      confidence interval [CI] 38% to 69%). Time taken for induction (hazard ratio 4.9;
      95% CI 2.2 to 10.9) and time taken for recovery (hazard ratio 2.8; 95% CI 1.5 to
      5.1) were lower among patients who received etomidate. The rates of adverse
      events were similar in both groups, except for myoclonus and pain at the
      injection site, which was more frequent in the etomidate group. CONCLUSION:
      Induction and recovery times are shorter with etomidate compared with midazolam.
      At the dosages used for procedural sedation and analgesia among children with
      displaced extremity fracture, etomidate has higher efficacy in comparison with
      midazolam.

PMID- 16997681
TI  - Identifying hospitalized infants who have bronchiolitis and are at high risk for
      apnea.
AB  - STUDY OBJECTIVE: Young infants with bronchiolitis are at risk for apnea. We seek
      to determine the rate of apnea in young infants with bronchiolitis and evaluate
      the performance of a predefined set of risk criteria for identifying infants at
      high risk for the development of apnea. METHODS: We identified a retrospective
      cohort study of patients treated in the emergency department (ED) of an urban
      pediatric tertiary care hospital from November 1995 to June 2000. All infants
      younger than 6 months who met our study definition of bronchiolitis and were
      admitted to the hospital were included. We developed, a priori, a set of risk
      criteria for identifying patients at high risk for apnea. Children were
      considered to be at high risk for apnea if (1) they were born at full term and
      were younger than 1 month, (2) they were born preterm (<37 weeks estimated
      gestational age) and were younger than 48 weeks postconception, or (3) the
      child's parents or a clinician had already witnessed an apnea episode with this
      illness before inpatient admission. Data pertaining to these risk criteria were
      collected from the ED physician's note. The primary outcome variable, the
      development of inhospital apnea, was assessed by review of the inpatient
      discharge summaries and medical records. RESULTS: Nineteen of 691 (2.7%; 95%
      confidence interval [CI] 1.7% to 4.3%) infants admitted with bronchiolitis
      developed apnea while hospitalized. All 19 patients with apnea were identified by
      our risk criteria (100% sensitivity; 1-sided 97.5% CI 82% to 100%). No patient
      classified as low risk subsequently developed apnea (100% negative predictive
      value; 1-sided 97.5% CI 99% to 100%). CONCLUSION: The rate of apnea among young
      infants hospitalized with bronchiolitis is low. Our clinical risk criteria
      successfully identified a low-risk group of infants whose risk of apnea is less
      than 1%.

PMID- 16997682
TI  - Nonketotic hyperglycemic coma in toddlers after unintentional methadone
      ingestion.
AB  - Methadone overdoses are increasing in parallel with the increased frequency of
      opiate substitution therapy in adults. Although unintentional methadone
      intoxication in children is rare, it is becoming more frequently recognized. We
      report 3 cases of unintentional methadone overdose in toddlers who initially
      displayed central nervous system depression associated with severe nonketotic
      hyperglycemia and discuss the possible pathophysiologic mechanisms of an
      underrecognized symptom of opiate intoxication in young children.

PMID- 16997683
TI  - Survey of California emergency departments about practices for management of
      suicidal patients and resources available for their care.
AB  - STUDY OBJECTIVE: To determine the resources available and current practices for
      the treatment of patients with suicidal ideation or attempts in California
      emergency departments (EDs). METHODS: We conducted a mail and e-mail survey of
      the directors of all 346 EDs in the state of California. Data collected included
      identification of hospital and respondent, type of hospital, presence of separate
      psychiatric ED, total number of ED patients and number of ED patients with
      suicidal ideation or attempts who were treated per week, mental health personnel
      on call to evaluate suicidal patients, criteria for patient disposition,
      available disposition options, delays in patient care, changes desired in the ED
      treatment of suicidal patients, and adequacy of community resources for suicidal
      patients. RESULTS: Two hundred twenty-three of 346 (64.5%) ED directors responded
      to the survey. Overall, the mean estimate of the proportion of ED visits by
      suicidal patients was 1.7%. Though evaluation of patients with suicidal ideation
      by a mental health professional was the usual practice, 51 respondents (23%)
      reported that they occasionally send patients with suicidal ideation home without
      such an evaluation, and 8.5% reported this was done more than 10% of the time. No
      single type of mental health professional, including psychiatrist, social worker,
      county or private psychiatric evaluation team, psychiatric nurse, or
      psychologist, was available for evaluation of suicidal patients in more than 50%
      of respondent EDs. In the majority of EDs, psychiatric evaluations were performed
      by either mobile county or private psychiatric evaluation teams or social workers
      on call to the ED. Psychiatrists were reported to evaluate the majority of
      suicidal patients in only 10% of EDs. Only 27% of respondents had the ability to
      admit patients to a psychiatric service at their hospital. When patients needed
      to be transferred, the estimated mean wait for these transfers was 7 hours.
      Seventy-one percent of respondents reported needing improved access to mental
      health personnel for evaluation of suicidal patients; 61% reported needing
      improved access to mental health personnel for patient disposition. CONCLUSION:
      In California EDs, there are limited mental health services for suicidal
      patients. Regional solutions to emergency and nonemergency mental health problems
      are needed, including improved access to mental health personnel for ED
      evaluation, disposition, and follow-up of suicidal patients and community mental
      health resources for patient referrals.

PMID- 16997684
TI  - A clinical tool for assessing risk after self-harm.
AB  - STUDY OBJECTIVE: Our aim is to develop a risk-stratification model for use by
      emergency department (ED) clinical staff in the assessment of patients attending
      with self-harm. METHODS: Participants were patients who attended 5 EDs in
      Manchester and Salford, England, after self-harm between September 1, 1997, and
      February 28, 2001. Social, demographic, and clinical information was collected
      for each patient at each attendance. With data from the Manchester and Salford
      Self-Harm Project, a clinical decision rule was derived by using recursive
      partitioning to discriminate between patients at higher and lower risk of
      repetition or subsequent suicide occurring within 6 months. Data from 3 EDs were
      used for the derivation set. The model was validated with data from the remaining
      2 EDs. RESULTS: Data for 9,086 patients who presented with self-harm were
      collected during this study period, including 17% that reattended within 6 months
      and 22 patients who died by suicide within 6 months. A 4-question rule, with a
      sensitivity of 94% (92.1-95.0% [95% confidence interval]) and specificity of 25%
      (24.2-26.5% [95% confidence interval]), was derived to identify patients at
      higher risk of repetition or suicide. CONCLUSION: Application of this simple,
      highly sensitive rule may facilitate assessment in the ED and help to focus
      psychiatric resources on patients at higher risk.

PMID- 16997685
TI  - Improving the design of the assessment of emergency department patients at risk
      for self-harm.

PMID- 16997686
TI  - Commentary: Speeding: socially acceptable but often fatal.

PMID- 16997688
TI  - Images in emergency medicine. Reexpansion pulmonary edema.

PMID- 16997689
TI  - Emergency physician survey: recombinant tissue plasminogen activator for stroke.

PMID- 16997690
TI  - Non-invasive carbon monoxide measurement is not accurate.

PMID- 16997692
TI  - Covert administration of psychotropic medications in the emergency department: an
      opposing view.

PMID- 16997693
TI  - Research overdue on subterfuge versus forced treatment in psychiatric
      emergencies.

PMID- 16997695
TI  - Thinking big.

PMID- 16997696
TI  - Medical services coding. American College of Emergency Physicians.

PMID- 16997697
TI  - Assignment of benefits. American College of Emergency Physicians.

PMID- 16997698
TI  - Pediatric mental health emergencies in the emergency medical services system.
      American College of Emergency Physicians.
AB  - Emergency departments (EDs) are vital in the management of pediatric patients
      with mental health emergencies (MHE). Pediatric MHE are an increasing part of
      emergency medical practice because EDs have become the safety net for a
      fragmented mental health infrastructure which is experiencing critical shortages
      in services in all sectors. EDs must safely, humanely, and in a culturally and
      developmentally appropriate manner manage pediatric patients with undiagnosed and
      known mental illnesses including those with mental retardation, autistic spectrum
      disorders, attention deficit hyperactivity disorder (ADHD), and those
      experiencing a behavioral crisis. EDs also manage patients with suicidal
      ideation, depression, escalating aggression, substance abuse, post traumatic
      stress disorder, maltreatment, and those exposed to violence and unexpected
      deaths. EDs must address not only the physical but also the mental health needs
      of patients during and after mass casualty incidents and disasters. The American
      Academy of Pediatrics and the American College of Emergency Physicians support
      the following actions: advocacy for increased mental health resources, including
      improved pediatric mental health tools for the ED, increased mental health
      insurance coverage, adequate reimbursement at all levels; acknowledgment of the
      importance of the child's medical home, and promotion of education and research
      for mental health emergencies.

PMID- 16997699
TI  - EMTALA and on-call responsibility for emergency department patients. American
      College of Emergency Physicians.

PMID- 16997700
TI  - Emergency ultrasound imaging criteria compendium. American College of Emergency
      Physicians.

PMID- 16997702
TI  - Medical screening of emergency department patients. American College of Emergency
      Physicians.

PMID- 16997703
TI  - The role of the legacy emergency physician in the 21st century. American College
      of Emergency Physicians.

PMID- 16997704
TI  - Physician credentialing and delineation of clinical privileges in emergency
      medicine. American College of Emergency Physicians.

PMID- 16997706
TI  - Physiologic characterisation of glioblastoma multiforme using MRI-based hypoxia
      mapping, chemical shift imaging, perfusion and diffusion maps.
AB  - PURPOSE: A multiparametric, physiologic MRI approach was considered to more
      completely characterise biopsy-confirmed glioblastoma multiforme (GBM). Chemical
      shift imaging (CSI) supplied biochemical information in metabolite ratios, while
      perfusion images provided data on presumed vascularity from regional cerebral
      blood volume (rCBV) and permeability maps. Diffusion-weighted images were reduced
      to apparent diffusion coefficient (ADC) maps to evaluate cellularity, and blood
      oxygen level-dependent imaging was used to create maps of putative hypoxic
      regions. METHODS: Six post-treatment GBM patients were scanned at 3-month
      intervals until recurrence was suggested by conventional MRI parameters, yielding
      20 scans for consideration. The percentage of extreme values in each technique
      that overlapped with other parameters was measured and compared across
      hemispheres to assess utility. RESULTS: We found significantly better performance
      in selecting the diseased hemisphere for overall percent overlap when compared to
      voxel counts from individual thresholded parameter maps. Parameters were selected
      on the basis of highest overlap, and corresponding composite overlap maps show
      increased specificity to likely recurrent regions by reducing the number of
      falsely positive voxels, and offer insight into relationships between various
      parameters. CONCLUSION: In a pilot group of patients, percent overlap appears to
      be sensitive to recurrent disease. When used to combine multiple parameters,
      voxels containing overlap can specifically target probable recurrent areas.

PMID- 16997707
TI  - Chronic subdural haematomas and anticoagulation or anti-thrombotic therapy.
AB  - Eighty-one cases of chronic subdural haematomas (CSDH) admitted to the
      neurosurgical unit of the Royal Hobart Hospital, Tasmania, Australia, over a 5
      year period were reviewed. The use of anticoagulant therapy as a causative agent
      in the development of CSDH was investigated. We suspected a high incidence of
      anticoagulant or anti-thrombotic therapy. We found that anticoagulant therapy was
      used by a significant percentage of CSDH patients. In the patient group
      presenting to our unit the risk of developing a CSDH was at least 42.5 times
      higher in warfarinised patients and also increased for patients on aspirin,
      although this risk could not be quantified.

PMID- 16997708
TI  - Pathogen recognition and development of particulate vaccines: does size matter?
AB  - The use of particulate carriers holds great promise for the development of
      effective and affordable recombinant vaccines. Rational development requires a
      detailed understanding of particle up-take and processing mechanisms to target
      cellular pathways capable of stimulating the required immune responses safely.
      These mechanisms are in turn based on how the host has evolved to recognize and
      process pathogens. Pathogens, as well as particulate vaccines, come in a wide
      range of sizes and biochemical compositions. Some of these also provide 'danger
      signals' so that antigen 'senting cells (APC), usually dendritic cells (DC),
      acquire specific stimulatory activity. Herein, we provide an overview of the
      types of particles currently under investigation for the formulation of vaccines,
      discuss cellular uptake mechanisms (endocytosis, macropinocytosis, phagocytosis,
      clathrin-dependent and/or caveloae-mediated) for pathogens and particles of
      different sizes, as well as antigen possessing and presentation by APC in
      general, and DC in particular. Since particle size and composition can influence
      the immune response, inducing humoral and/or cellular immunity, activating CD8 T
      cells and/or CD4 T cells of T helper 1 and/or T helper 2 type, particle
      characteristics have a major impact on vaccine efficacy. Recently developed
      methods for the formulation of particulate vaccines are presented in this issue
      of Methods, showcasing a range of "cutting edge" particulate vaccines that employ
      particles ranging from nano to micro-sized. This special issue of Methods further
      addresses practical issues of production, affordability, reproducibility and
      stability of formulation, and also includes a discussion of the economic and
      regulatory challenges encountered in developing vaccines for veterinary use and
      for common Third World infectious diseases.

PMID- 16997709
TI  - Microparticle-based technologies for vaccines.
AB  - Microparticles have been effectively used for many years as delivery systems for
      drugs and therapeutic proteins. Their application to the delivery of vaccines is
      not as extensive, but is growing. Utility has been demonstrated for the delivery
      of various types of vaccines (e.g., recombinant proteins, plasmid DNA, and
      peptides) and other vaccine components (e.g., immune potentiators). With respect
      to delivery of immune potentiators, synergistic effects are often observed
      whereby much more potent immune responses are induced with a combination than
      with either component alone. Hence, the prospects for broad application of
      microparticle-based delivery systems for vaccines are excellent.

PMID- 16997710
TI  - Methods for nano-particle based vaccine formulation and evaluation of their
      immunogenicity.
AB  - Nano- and microparticles have long been used for the delivery of drugs and are
      currently being evaluated as vaccine delivery systems. Particulates can elicit
      potent immune responses, either by direct immuno-stimulation of antigen
      presenting cells (APC) or/and by delivering antigen to specific cellular
      compartments and promoting antigen uptake by appropriate stimulatory cell types.
      Herein, we describe a detailed method for the preparation of a novel nanoparticle
      based antigen delivery system which induces strong cellular and humoral immune
      responses in mice and sheep. This simple system is based on the use of 40
      nanometer (nm) inert solid carrier beads to which antigen is covalently coupled
      before injection. Covalent conjugation of antigen to the nanobeads, assessment of
      conjugation efficiency, characterisation and measurement of in vivo
      immunogenicity by cytokine ELISPOT (to measure antigen-specific T-cell responses)
      and ELISA (to measure antibody titers), are described. Emphasis is placed on
      providing trouble-shooting advice to enable the reproducible production of
      soluble nano-size formulations that do not suffer from common problems such as
      aggregation, as well as understanding the causes and thus avoiding a range of
      prevalent technical problems that occur when using immune response detection
      assays, such as the cytokine ELISPOT assay and ELISA.

PMID- 16997711
TI  - Lyophilisation and sterilisation of liposomal vaccines to produce stable and
      sterile products.
AB  - The advantages of liposomes as delivery systems for peptide, protein and DNA
      vaccines is well-recognised, unfortunately their application has been stinted by
      their instability during storage and their limited shelf-life. Further,
      sterilisation of these systems has been problematic, with degradation of the
      liposomes being reported after sterilisation using the various techniques
      available. Work form our laboratory has investigated techniques that can be
      applied to particulate liposomal vaccines such that they can be prepared in a
      freeze-dried and sterile format. In this article, we describe techniques for the
      lyophilisation, cryoprotection and sterilisation of liposomal vaccines. Applying
      these methods allows for the retention of both the chemical integrity of the
      lipids and the key physico-chemical characteristics of the liposomes (e.g.,
      particle size, zeta potential, and dynamic viscosity), thus supporting the
      enhanced transition of liposomal vaccines from the bench to the clinic.

PMID- 16997712
TI  - Liposomal vaccines--targeting the delivery of antigen.
AB  - Vaccines that can prime the adaptive immune system for a quick and effective
      response against a pathogen or tumor cells, require the generation of antigen
      (Ag)-specific memory T and B cells. The unique ability of dendritic cells (DCs)
      to activate naive T cells, implies a key role for DCs in this process. The
      generation of tumor-specific CD8(+) cytotoxic T cells (CTLs) is dependent on both
      T cell stimulation with Ag (peptide-MHC-complexes) and costimulation.
      Interestingly, tumor cells that lack expression of T cell costimulatory molecules
      become highly immunogenic when transfected to express such molecules on their
      surface. Adoptive immunotherapy with Ag-pulsed DCs also is a strategy showing
      promise as a treatment for cancer. The use of such cell-based vaccines, however,
      is cumbersome and expensive to use clinically, and/or may carry risks due to
      genetic manipulations. Liposomes are particulate vesicular lipid structures that
      can incorporate Ag, immunomodulatory factors and targeting molecules, and hence
      can serve as potent vaccines. Similarly, Ag-containing plasma membrane vesicles
      (PMV) derived from tumor cells can be modified to incorporate a T cell
      costimulatory molecule to provide both TCR stimulation, and costimulation. PMVs
      also can be modified to contain IFN-gamma and molecules for targeting DCs,
      permitting delivery of both Ag and a DC maturation signal for initiating an
      effective immune response. Our results show that use of such agents as vaccines
      can induce potent anti-tumor immune responses and immunotherapeutic effects in
      tumor models, and provide a strategy for the development of effective vaccines
      and immunotherapies for cancer and infectious diseases.

PMID- 16997713
TI  - Saponin-adjuvanted particulate vaccines for clinical use.
AB  - Saponins are well recognised as potent immune stimulators, but their
      applicability as vaccine adjuvants have been limited due to associated toxicity.
      Formulation of saponin adjuvant with cholesterol and phospholipid produces the
      particulate ISCOMATRIX adjuvant, and when antigen is also contained within the
      particle, an ISCOM vaccine is produced. These particulate vaccines retain the
      adjuvant activity of the saponin component but without toxicity. Saponin
      adjuvanted particulate vaccines have significant potential as a novel strategy in
      vaccine development. This review discusses (i) recent methodologies which have
      attempted to increase the flexibility and applicability of this technology by
      modifying either the vaccine composition or the mode of formulation; (ii) recent
      evaluations of these technologies for inducing protection against infectious
      diseases and as cancer immunotherapeutics.

PMID- 16997714
TI  - Virus-like particles: passport to immune recognition.
AB  - Virus-like particles (VLPs) are formed by the self-assembly of envelope and/or
      capsid proteins from many viruses. In many cases such VLPs have structural
      characteristics and antigenicity similar to the parental virus, and some have
      already proven successful as vaccines against the cognate virus infection. The
      structural components of some VLPs have also proven amenable to the insertion or
      fusion of foreign antigenic sequences, allowing the production of chimeric VLPs
      exposing the foreign antigen on their surface. Other VLPs have been used as
      carriers for foreign antigens, including non-protein antigens, via chemical
      conjugation. This review outlines some of the advantages, disadvantages, and
      technical considerations for the use of a wide range of VLP systems in vaccine
      development.

PMID- 16997716
TI  - Economic and practical challenges to the formulation of vaccines against endemic
      infectious diseases such as malaria.
AB  - Herein, we analyze in general the current vaccine market and identify potential
      factors driving and modulating supply and demand for vaccines. An emphasis is
      placed on changes in regulation in the last 20 years which have led to increased
      indirect costs of production, and which can create a barrier against the timely
      use of technological advances to reduce direct costs. Other defining industry
      characteristics, such as firm numbers and sizes, cost and pricing strategies,
      nature extent and impact of Government involvement and international regulation
      are noted. These considerations, far from being removed from basic vaccine
      research, influence its ability to achieve aims that can be then progressed into
      effective vaccine products. We discuss specifically the development of
      particulate vaccines against malaria, a major lethal disease and health problem
      prevalent in Africa, including some key economic and methodological challenges
      and opportunities. We note some practical issues blocking the development of
      effective particulate vaccines for the Third World, mainly driven by the
      regulatory spiral noted above.

PMID- 16997717
TI  - Preclinical and clinical progress of particle-mediated DNA vaccines for
      infectious diseases.
AB  - This review provides an overview of studies employing particle-mediated epidermal
      delivery (PMED) or the gene gun to administer DNA vaccines for infectious
      diseases in preclinical studies employing large animal models and in human
      clinical trials. It reviews the immunogenicity and protective efficacy of PMED
      DNA vaccines in nonhuman primates and swine and studies that have directly
      compared the effectiveness of PMED in these large animal models to existing
      licensed vaccines and intramuscular or intradermal delivery of DNA vaccines with
      a needle. Various clinical trials employing PMED have been completed and an
      overview of the immunogenicity, safety, and tolerability of this approach in
      humans is described. Finally, efforts currently in progress for commercial
      development of particle-mediated DNA vaccines are discussed.

PMID- 16997715
TI  - Virus-like particles production in green plants.
AB  - Viruses-like particles (VLPs), assembled from capsid structural subunits of
      several different viruses, have found a number of biomedical applications such as
      vaccines and novel delivery systems for nucleic acids and small molecules.
      Production of recombinant proteins in different plant systems has been intensely
      investigated and improved upon in the last two decades. Plant-derived antibodies,
      vaccines, and microbicides have received great attention and shown immense
      promise. In the case of mucosal vaccines, orally delivered plant-produced VLPs
      require minimal processing of the plant tissue, thus offering an inexpensive and
      safe alternative to more conventional live attenuated and killed virus vaccines.
      For other applications which require higher level of purification, recent
      progress in expression levels using plant viral vectors have shown that plants
      can compete with traditional fermentation systems. In this review, the different
      methods used in the production of VLPs in green plants are described. Specific
      examples of expression, assembly, and immunogenicity of several plant-derived
      VLPs are presented.

PMID- 16997718
TI  - Virus-like particles: designing an effective AIDS vaccine.
AB  - Viruses that infect eukaryotic organisms have the unique characteristic of self
      assembling into particles. The mammalian immune system is highly attuned to
      recognizing and attacking these viral particles following infection. The use of
      particle-based immunogens, often delivered as live-attenuated viruses, has been
      an effective vaccination strategy for a variety of viruses. The development of an
      effective vaccine against the human immunodeficiency virus (HIV) has proven to be
      a challenge, since HIV infects cells of the immune system causing severe
      immunodeficiency resulting in the syndrome known as AIDS. In addition, the
      ability of the virus to adapt to immune pressure and reside in an integrated form
      in host cells presents hurdles for vaccinologists to overcome. A particle-based
      vaccine strategy has promise for eliciting high titer, long-lived, immune
      responses to a diverse number of viral epitopes against different HIV antigens.
      Live-attenuated viruses are effective at generating both cellular and humoral
      immune responses. However, while these vaccines stimulate immunity, challenged
      animals rarely clear the viral infection and the degree of attenuation directly
      correlates with protection from disease. Further, a live-attenuated vaccine has
      the potential to revert to a pathogenic form. Alternatively, virus-like particles
      (VLPs) mimic the viral particle without causing an immunodeficiency disease. VLPs
      are self-assembling, non-replicating, non-pathogenic particles that are similar
      in size and conformation to intact virions. A variety of VLPs for lentiviruses
      are currently in preclinical and clinical trials. This review focuses on our
      current status of VLP-based AIDS vaccines, regarding issues of purification and
      immune design for animal and clinical trials.

PMID- 16997719
TI  - Particulate delivery systems for animal vaccines.
AB  - The requirements for veterinary vaccines are different to those of human
      vaccines. Indeed, while more side effects can be tolerated in animals than in
      humans; there are stricter requirements in terms of cost, ease of delivery
      (including to wildlife), and a need to develop vaccines in species for which
      relatively little is known in terms of molecular immunology. By their nature
      particulate vaccine delivery systems are well suited to address these challenges.
      Here, we review particulate vaccine delivery systems, ranging from cm-sized long
      distance ballistic devices to nano-bead technology for veterinary species and
      wildlife.

PMID- 16997720
TI  - Should there be a training psychoanalyst status?

PMID- 16997721
TI  - The analyst's countertransference to the psychoanalytic process.
AB  - There is countertransference, not just to individual patients, but to the process
      of psychoanalysis itself. The analytic process is a contentious topic.
      Disagreements about its nature can arise from taking it as a unitary concept that
      should have a single definition whereas, in fact, there are several strands to
      its meaning. The need for the analyst's free associative listening, as a
      counterpart to the patient's free associations, implies resistance to the
      analytic process in the analyst as well as the patient. The author gives examples
      of the self-analysis that this necessitates. The most important happenings in
      both the analyst's and the patient's internal worlds lie at the boundary between
      conscious and unconscious, and the nature of an analyst's interventions depends
      on how fully what happens at that boundary is articulated in the analyst's
      consciousness. The therapeutic quality of an analyst's engagement with a patient
      depends on the freeing and enlivening quality, for the analyst, of the analyst's
      engagement with his or her countertransference to the analytic process.

PMID- 16997722
TI  - The controversial discussions and apres-coup.
AB  - The author suggests a distinction between what is descriptively named apres-coup,
      and what is dynamically identified as apres-coup. This parallels Freud's
      distinction between the descriptive unconscious and the dynamic unconscious in
      the topographical model of the mind. The descriptive apres-coup refers to the way
      in which the concept has found a use, especially but not only in the French
      literature, to refer to retrospective signification in the moment-to-moment
      progress of a session. The author outlines dynamic apres-coup and she suggests it
      is at the core of Freudian metapsychology. Dynamic apres-coup establishes a link
      between trauma, castration, repetition compulsion, sexuality and temporality in
      the context of the transference.

PMID- 16997723
TI  - The emotional experience of K.
AB  - The author raises the question of the emotional experience of K in Bion's schema
      of affective links, L, H, and K, suggesting that it is the emotional experience
      of feeling curious. He explores the central role curiosity has in 'On arrogance'
      and 'Attacks on linking' and hypothesizes that in Learning from experience the
      more complex notion of K is introduced in its place. Thus, Bion's affective
      schema is taken to be a version of Freud's account of experience in terms of
      instinctual impulses recast in terms of emotional experience. Freud's primary
      developmental dichotomy, the tensions between the pleasure principle and the
      reality principle, can be seen as the dichotomy of tensions between the emotional
      experience of L/H and the emotional experience of K. This suggests that the
      potential tension between K and L/H is critical to what happens in the consulting
      room. Finally the author argues that containing as a developmental dynamic is an
      expression of a K-state-of-mind and thus the container is thus a container-in-K.
      It concludes that one important aspect of what Bion called -K is an attack on a K
      state-of-mind by an intrusion of L/H which has the effect of contaminating and
      dominating the urge to know.

PMID- 16997724
TI  - Vicissitudes in adult life resulting from traumatic experiences in adolescence.
AB  - The author deals with the difficulties in combining the concepts of trauma and
      phantasy. He evaluates Freudian observations relating to chance and trauma. He
      considers traumatic effects of chance in relation to the rupture of a
      narcissistic phantasy of invulnerability. The narrating of traumatic events may
      awaken in the analyst tendencies to repeat the aggression of these traumatic
      events towards the subject. The accusatory interpretation can be one of the means
      by which this repetition is established. The author explores a type of trauma
      which is essentially related to the disturbance of the structure which contains
      the ideals of the subject. This disturbance is a consequence of disillusionment
      resulting from the loss of an object who was the depository of these ideals.
      Trauma generates a state of mourning for lost ideals. The author describes
      traumatic events which occurred in a patient's life at puberty; paradoxical
      behaviours in the patient's parents caused the patient to have new traumas. The
      reluctance to explore the derivatives of the unconscious, and to investigate
      possible meaning in symbols, was a central problem in this patient's analysis.
      The author discusses disturbances in symbolization, and he examines the subject
      of projective identifications that were received by patients from their primary
      objects.

PMID- 16997725
TI  - A psychoanalytic understanding of the desire for knowledge as reflected in
      Freud's Leonardo da Vinci and a memory of his childhood.
AB  - The author offers an understanding of the psychoanalytic notion of the desire for
      knowledge and the possibility of attaining it as it fi nds expression in Freud's
      Leonardo da Vinci and a memory of his childhood. This understanding has not been
      explicitly articulated by Freud but may be considered integral to psychoanalysis'
      Weltanschauung as shaped by Freud's legacy. It emerges through an attempt to
      explain basic shifts, contradictions, inconsistencies and tensions that become
      apparent from a close reading of the text of Leonardo. Articulating this implicit
      understanding of knowledge provides the grounds for a stance on epistemology that
      is integral to psychoanalysis and relevant to contemporary psychoanalytic
      concerns on this topic. This epistemology focuses on the necessary involvement of
      passion, rather than detachment, in the search for knowledge and views the
      psychoanalytic aim of self-knowledge as a derivative, and most immediate
      expression, of a broader and more basic human drive to know.

PMID- 16997726
TI  - Cultural function and psychological transformation in psychoanalysis and
      psychoanalytic psychotherapy.
AB  - Cultural experience of silence and individual vicissitudes between talking and
      being silent influence the way individuals form an alliance and pursue the
      analytic process. This is of relevance both for the patient and for the
      psychoanalyst/therapist. The author describes a patient, whose silent phase
      occurred in the fifth and sixth year of intensive psychoanalytic psychotherapy.
      She suggests that a) the silence functioned as a protection of a space for the
      core self and promoted inner transformation and psychological development; b) the
      silence involved a transference-countertransference matrix with projective
      identifications of the patient's internalized mother- and father-related objects
      that caused a tenuous balance between maintaining and erasing the relationship
      between the patient and the author; c) the silence phase was highly influenced by
      the author's own cultural background and what she brought into the relationship
      of tolerance of being silent in the presence of another, and understanding of the
      many complex functions of silence. During the silent phase the patient moved from
      simply describing and naming her affects and inner experiences or expressing them
      as somatic processes, to being able to internally access and verbally convey her
      own affects and experiences in the therapeutic alliance. This process involved
      both affect desomatization, affect differentiation, and affect verbalization.

PMID- 16997727
TI  - Critical reflections on intersubjectivity in psychoanalysis.
AB  - The authors review the philosophical trend known as postmodernism and the way it
      has influenced a part of psychoanalytic thought, concluding with some comments on
      the qualities and shortcomings of the new developments. The authors consider the
      origins and the cultural and aesthetic-philosophical meaning of postmodernism,
      identifying some key concepts such as deconstructionism, the disappearance of the
      'individual subject' and individual identity, and the rejection of 'in-depth'
      models of psychoanalysis. Then they examine various, wide-ranging developments in
      psychoanalytic thought and treatment. They review the intersubjective field in
      psychoanalysis, especially in the USA, and then explore whether the underlying
      lack of truth to be discovered, stressed by these 'new view' statements, or the
      fact that the 'truth' only exists in linguistic-narrative constructions is
      consistent with basic analytic concepts such as the unconscious, phantasy,
      transference and countertransference, which recall the tri-dimensional nature of
      inner psychic reality. The psychoanalytic process is a condition activated
      through a bond that is able to hold and contain the relationship of the analytic
      couple and the patient's unconscious world and not through hermeneutic or
      narrative constructions.

PMID- 16997728
TI  - Art and emotion in psychoanalysis.
AB  - Freud's view that art satisfies psychic needs has been taken to mean that art has
      its source in the unconscious and that it unifies pleasure and reality. The
      author argues that there is a third point that Freud repeatedly emphasizes, which
      should not be overlooked, that art influences our emotions. The author examines
      what Freud means by this claim, in particular, his reading of Michelangelo's
      Moses. Freud's focus here on emotions as fundamental to subjective experience, as
      subject to regulation and as potentially healthy forms of communication serves to
      supplement and even challenge what he says in his theory of affect. The author
      concludes by making inferences about a contemporary psychoanalytic theory of
      affects: that it ought to be inclusive of science (more receptive to neurobiology
      and less bound to Freud) as well as art (preserving the focus on subjective
      experience, especially the processing of complex emotions), which is illustrated
      with the concept of mentalized affectivity.

PMID- 16997729
TI  - Nascent body ego: metapsychological and neurophysiological aspects.
AB  - For Freud, body ego was the organizing basis of the structural theory. He defined
      it as a psychic projection of the body surface. Isakower's and Lewin's classical
      findings suggest that the body surface experiences of nursing provide the infant
      with sensory-affective stimulation that initiates a projection of sensory
      processes towards the psychic realm. During nursing, somato-sensory, gustatory
      and olfactory modalities merge with a primitive somatic affect of satiation,
      whereas auditory modality is involved more indirectly and visual contact more
      gradually. Repeated regularly, such nascent experiences are likely to play a part
      in the organization of the primitive protosymbolic mental experience. In support
      of this hypothesis, the authors review findings from a neurophysiological study
      of infants before, during and after nursing. Nursing is associated with a
      significant amplitude change in the newborn electroencephalogram (EEG), which
      wanes before the age of 3 months, and is transformed at the age of 6 months into
      rhythmic 3-5 Hz hedonic theta-activity. Sucking requires active physiological
      work, which is shown in a regular rise in heart rate. The hypothesis of a sensory
      affective organization of the nascent body ego, enhanced by nursing and active
      sucking, seems concordant with neurophysiological phenomena related to nursing.

PMID- 16997730
TI  - What is conceptual research in psychoanalysis?
AB  - The development of psychoanalysis as a science and clinical practice has always
      relied heavily on various forms of conceptual research. Thus, conceptual research
      has clarified, formulated and reformulated psychoanalytic concepts permitting to
      better shape the findings emerging in the clinical setting. By enhancing clarity
      and explicitness in concept usage it has facilitated the integration of existing
      psychoanalytic thinking as well as the development of new ways of looking at
      clinical and extraclinical data. Moreover, it has offered conceptual bridges to
      neighbouring disciplines particularly interested in psychoanalysis, e.g.
      philosophy, sociology, aesthetics, history of art and literature, and more
      recently cognitive science/neuroscience. In the present phase of psychoanalytic
      pluralism, of worldwide scientific communication among psychoanalysts
      irrespective of language differences and furthermore of an intensifying dialogue
      with other disciplines, the relevance of conceptual research is steadily
      increasing. Yet, it still often seems insufficiently clear how conceptual
      research can be differentiated from clinical and empirical research in
      psychoanalysis. Therefore, the Subcommittee for Conceptual Research of the IPA
      presents some of its considerations on the similarities and the differences
      between various forms of clinical and extraclinical research, their specific
      aims, quality criteria and thus their specific chances as well as their specific
      limitations in this paper. Examples taken from six issues of the International
      Journal of Psychoanalysis in 2002-3 serve as illustrations for seven different
      subtypes of conceptual research.

PMID- 16997731
TI  - Revisiting Groundhog day (1993): cinematic depiction of mutative process.

PMID- 16997733
TI  - Editorial: the Journal of COPD--new directions in disease understanding and
      management.

PMID- 16997734
TI  - Trends and ethnic differences in COPD hospitalization and mortality in Singapore.
AB  - STUDY OBJECTIVE: COPD mortality alone among major causes of diseases continues to
      rise in most countries worldwide. We examine trends, and gender and ethnic
      differences in COPD hospitalization and mortality in Singapore from 1991 to 1998,
      and examine possible explanations. DESIGN: Analysis of population-based health
      administrative data. SETTING: Multi-ethnic (Chinese, Malay and Indian) population
      of Singapore (3 million population). METHOD: Data on hospitalizations and deaths
      due to COPD as the underlying cause (ICD codes 491, 492, 496), extracted from
      national databases, were used to calculate age-specific and standardized rates
      for the population aged 55 + years. COPD accounted for 4.6% of total deaths (5.8%
      in those aged 55 +), and 1.02% of all hospitalizations (3.1% in those aged 55 +).
      RESULTS: COPD mortality in 1998 decreased steeply by -43.7% from 1991 (a decline
      that continued a steady trend since 1970), while hospitalization showed little
      significant change (-3.3%). Men had 4 and 5 times higher mortality and
      hospitalization, and also showed less favorable trends than women. Malays,
      especially males, showed the highest level and least favorable decline of
      mortality. CONCLUSION: Exceptionally steady declines in COPD mortality rates, and
      stable rates of hospitalization are observed in Singapore in the 1990s. Differing
      levels and trends of hospitalization and mortality by gender and ethnicity are
      related to known demographic variations and trends of smoking prevalence in the
      country.

PMID- 16997735
TI  - Cigarette smoke stimulates MMP-1 production by human lung fibroblasts through the
      ERK1/2 pathway.
AB  - An imbalance between proteases and anti-proteases is believed to play an
      important role in the pathogenesis of emphysema. In this study, we explored the
      hypothesis that cigarette smoke can alter tissue structure through an effect on
      the release of matrix metalloproteinase-1 (MMP-1) and type I tissue inhibitor of
      metalloproteinases (TIMP-1). Cigarette smoke extract (CSE) significantly
      stimulated pro-MMP-1 production (determined by ELISA and immunoblots) and mRNA
      expression (by real-time RT-PCR) by human fetal lung fibroblasts (HFL-1) in a
      concentration-dependent manner (2.5-10%). High concentrations of CSE (10%) could
      potentially activate the latent form of MMP-1 as the high molecular weight (52
      kDa) form was converted into a low molecular weight (42 kDa) form consistent with
      active MMP-1. TIMP-1 production, however, was not significantly altered by the
      concentrations of CSE tested. After 30 min exposure, CSE significantly induced
      ERK1/2 phosphorylation, which then gradually decreased from 90 minutes to 3
      hours. PD98059, a specific inhibitor of ERK-MAPK, significantly blocked the CSE
      effect on ERK1/2 phosphorylation. Furthermore, PD98059 significantly inhibited
      the CSE effect on MMP-1 production and mRNA expression by fibroblasts. These
      results suggest that cigarette smoke stimulates production and likely activates
      MMP-1 through activating ERK1/2 signal transduction pathway. By inducing MMP-1,
      cigarette smoke may result in excess tissue destruction and contribute to the
      development of emphysema.

PMID- 16997736
TI  - N-acetylcysteine treatment protects against VEGF-receptor blockade-related
      emphysema.
AB  - Administration of the VEGF receptor blocker SU5416 to rats causes alveolar septal
      cell apoptosis and emphysema; both can be prevented by a superoxide dismutase
      mimetic. Here we show that SU5416 induces the expression of heme oxygenase-1 in
      the lung tissue and that administration of antioxidant N-acetyl-l-cysteine
      protects alveolar septal cells against apoptosis, as demonstrated by caspase-3
      lung immunohistochemistry, and against emphysema.

PMID- 16997737
TI  - Comparison of oral and depot intra-muscular steroids in assessing steroid
      responsiveness in COPD.
AB  - Non-compliance or euphoria may limit the usefulness of prednisolone tablets in
      assessing steroid-responsiveness in chronic obstructive pulmonary disease (COPD).
      Depot intra-muscular methyl-prednisolone (imMP), producing a plateau steroid
      effect over two weeks, may be more reliable. Following two weeks of placebo,
      twenty-seven COPD patients (mean FEV 1 43% predicted) participated in a two-week
      randomised, double-blind, placebo-controlled, parallel-design trial taking either
      120 mg imMP with placebo tablets or placebo injection with prednisolone 30 mg
      daily. After each period, post-bronchodilator FEV 1, forced vital capacity (FVC),
      inspiratory capacity (IC) and six-minute walking distance (6MWD) were assessed
      and patients completed both quality-of-life scores (St. George's 30 and Short
      Form 36) and mood scores (Hospital Anxiety and Depression scores and Altman's
      Self-rating Mania Scale). There were no significant changes in 6MWD, quality of
      life or mood scores after either type of steroids and no change in lung function
      after imMP. By contrast, there were small mean improvements in lung function on
      oral prednisolone (mean FEV 1, FVC and IC increased by 100, 320 and 150 ml,
      respectively). Only the improvement in FVC was significantly greater after
      prednisolone compared with imMP. Single depot intra-muscular injections of
      steroids have no advantage over oral daily prednisolone in testing steroid
      responsiveness in COPD patients.

PMID- 16997738
TI  - Outcome measures for COPD treatments: a critical evaluation.

PMID- 16997739
TI  - Alveolar macrophages as orchestrators of COPD.
AB  - Alveolar macrophages play a critical role in the pathophysiology of COPD and are
      a major target for future anti-inflammatory therapy. Macrophage numbers are
      markedly increased in the lung and alveolar space of patients with COPD and are
      localized to sites of alveolar destruction. The increased numbers of macrophages
      may result from increased recruitment of blood monocytes, prolonged survival in
      the lung and to a lesser extent to increased proliferation in the lung. Alveolar
      macrophages from COPD patients have an increased baseline and stimulated
      secretion of inflammatory proteins, including certain cytokines, chemokines,
      reactive oxygen species and elastolytic enzymes, which together could account for
      all of the pathophysiological features of COPD. Alveolar macrophages form COPD
      appear to be resistant to the anti-inflammatory effects of corticosteriods and
      this is linked to reduced activity and expression of histone deacetylase 2, a
      nuclear enzyme that switches off inflammatory genes activated through the
      transcription factor nuclear factor-KB. Alternative anti-inflammatory therapies
      that inhibit macrophages are therefore needed in the future to deal with the
      chronic inflammation of COPD. These drugs may include resveratrol, theophylline
      derivatives, MAP kinase inhibitors and phosphodiesterase-4 inhibitors.

PMID- 16997740
TI  - What we owe to alpha(1)-antitrypsin and to Carl-Bertil Laurell.
AB  - The archetypal status of alpha(1)-antitrypsin in biology and medicine grew from
      the finding, thirty years ago, by Carl-Bertil Laurell, of the association of its
      deficiency with emphysema. In biology, alpha(1)-antitrypsin now provides the
      model for both the structure and the remarkable mechanism of the serpin protease
      inhibitors that control the key proteolytic pathways of the body. In medicine,
      the plasma deficiency of alpha(1)-antitrypsin has drawn attention to protease
      antiprotease imbalance as a contributory cause of chronic obstructive pulmonary
      disease. But even more significantly, the finding that the common genetic
      deficiency of alpha(1)-antitrypsin was also associated with the development of
      liver cirrhosis introduced the new entity of the conformational diseases. The
      proposal that the same general mechanism was responsible for the best known of
      the conformational diseases, the common late-onset dementias, was controversial.
      It was vindicated however by the recent finding that a mutation, which results in
      the liver aggregation of alpha(1)-antitrypsin, also results in a typical late
      onset dementia when it occurs in a brain-specific homologue of alpha(1)
      antitrypsin. The extensive development of such diverse fields of studies, each
      based on alpha(1)-antitrypsin, is a measure of the encouragement Laurell gave to
      younger colleagues in the field. It also reflects the great advantage of linked
      contributions from clinical as well as basic sciences. Time after time,
      scientific controversies and deadlocks have been solved by landmark clinical
      cases, which have revealed unexpected findings and insights, within and beyond
      the fields of study.

PMID- 16997741
TI  - Does mechanical injury of the peripheral airways play a role in the genesis of
      COPD in smokers?
AB  - In the present account it is proposed that in smokers the transition from
      peripheral airway disease to COPD is characterized by three sequential stages:
      Stage I, during which the closing volume eventually exceeds the functional
      residual capacity; Stage II, during which tidal expiratory flow limitation (EFL)
      is eventually exhibited; and Stage III, during which dynamic hyperinflation
      progressively increases leading to dyspnea and exercise limitation, which may be
      considered as markers of overt disease. Presence of airway closure (Stage I) and
      EFL (Stage II) in the tidal volume range may promote peripheral airway injury and
      accelerate the abnormalities of lung function. It is such injury that may
      determine which smoker is destined to develop COPD.

PMID- 16997742
TI  - Commentary--Pathophysiology of airflow obstruction: could there really be an
      early test of prognostic significance?
AB  - This article represents a commentary on a controversial hyphothesis described by
      Dr.Milic-Emili in this issue. The authors discuss the hyphothesis and suggest
      that a re-examination of longitudinal lung function data could prove or deny his
      suggestion.

PMID- 16997743
TI  - COPD and air travel.

PMID- 16997745
TI  - Global Strategy for the Diagnosis, Management, and Prevention of Chronic
      Obstructive Pulmonary Disease: GOLD Executive Summary updated 2003.

PMID- 16997748
TI  - Coupling between cerebellar hemispheres and sensory processing.

PMID- 16997749
TI  - Pannexin expression in the cerebellum.
AB  - Pannexin1 and pannexin2 are members of the pannexin gene family which are widely
      expressed in the central nervous system. Here we present an overview of pannexin
      expression and distribution in the mouse cerebellum. Pannexin1 and pannexin2 are
      expressed in the Purkinje cells and in some cells of the granule cell layer.
      Pannexin2 is also expressed in the stellate cells of the molecular layer. A
      differential expression of pannexin1 and pannexin2 mRNA is observed during
      cerebellar development. These findings constitute the first indication of the
      involvement of pannexin molecules in the developing cerebellum. Although the
      functional relevance of these molecules remains currently unknown, the abundance
      of pannexins in the Purkinje cells suggests that they may contribute to the
      generation of cerebellar rhythms.

PMID- 16997750
TI  - Molecular machinery governing GABAergic neuron specification in the cerebellum.
AB  - Although the cerebellum contains a relatively small variety of neurons, the
      molecular machinery governing neuronal generation and/or subtype specification is
      still poorly understood. We identified a novel mutant mouse, cerebelless, which
      lacks the entire cerebellar cortex but survives up to the adult stages. Analyses
      of its phenotypes and identification of its responsible gene clarified that Ptf1a
      (pancreas transcription factor 1a), which encodes a bHLH transcription factor, is
      involved in cerebellar GABAergic neuron production. Together with recently
      published papers describing another bHLH gene, Math1, our study proposes that two
      bHLH transcription factors, PTF1A and MATH1, may participate in regionalization
      of cerebellar neuroepithelium, defining two distinct areas, the ventricular zone
      and the rhombic lip, which generate GABAergic and glutamatergic neurons,
      respectively. Here I will describe a novel cerebellar mutant, cerebelless, review
      the role of Ptf1a in GABAergic neuron production, and discuss new insights into
      cerebellar development from the vantage point of regulation by bHLH transcription
      factors.

PMID- 16997751
TI  - Magnetic resonance imaging of fetal cerebellar development.
AB  - In the last few years fetal magnetic resonance imaging (MRI) has been proposed as
      a second level technique in the evaluation of fetal brain anomalies. It has been
      demonstrated that MRI is highly accurate in illustrating the morphologic changes
      of developing brain and fetal brain abnormalities being a useful procedure when
      ultrasonography is inconclusive or doubtful. Starting from the 19-20 weeks
      gestational age (GA), MRI can reliably depict fetal brain anatomy and locating
      pathology, offering a robust and reliable tool in the assessment of fetal CNS
      diseases. In this review both in vivo MRI quantitative and qualitative data about
      fetal cerebellar development are presented and compared with ultrasonography
      data. Fetal cerebellar development is gradual, steady, and largely comparable to
      the development of the supratentorial brain. Archicerebellar (flocculo-nodular
      lobe) and paleocerebellar (vermis) structures develop first, whereas
      neocerebellum (cerebellar hemispheres) develop slowly and largely after birth.

PMID- 16997752
TI  - Acquisition of simple auditory and visual sequences in cerebellar patients.
AB  - Previous studies suggest a role of the cerebellum in detecting and recognizing
      event sequences. In the present study sequences of two acoustic tones of
      different frequencies and sequences of two visual stimuli with different colours
      were presented with short, long and very long durations. Thirteen cerebellar
      patients and 13 controls were required to indicate whether the order of stimuli
      was identical or opposite to a reference by saying 'yes' or 'no'. To minimize
      motor requirements no time restrictions were given. In none of the test
      conditions a significant difference between patients and controls was observed.
      The results suggest that the cerebellum is not essential for acquisition of
      simple sensory sequences. Differences in findings between previous and the
      present study may be explained by differences in motor demands and the explicit
      nature of the tasks.

PMID- 16997753
TI  - Coupling between cerebellar hemispheres: behavioural, anatomic, and functional
      data.
AB  - Although the cerebellum has been related to emotional, cognitive, and sensory
      processes, its outstanding significance for motor behaviour has attracted a vast
      variety of studies. Specifically, the role of cerebellar activity for appropriate
      movement timing has been investigated intensively. Behavioural studies,
      particularly of patients following cerebellar lesions, gave rise to the
      hypothesis that each hand is controlled by separate timing mechanisms most likely
      localized within lateral portions of each cerebellar hemisphere. Reduced timing
      variability during simultaneous bimanual tasks implies that both timing signals
      are integrated prior to movement execution, probably by information transfer
      between both cerebellar hemispheres. However, this raises the question for
      functional and anatomic fundamentals of such an integration process. The present
      article reviews behavioural, functional, and anatomic data to shed light on
      possible interactions between both cerebellar hemispheres during the execution of
      timed motor behaviour.

PMID- 16997754
TI  - Activity-dependent modulation of inhibition in Purkinje cells by TrkB ligands.
AB  - In the cerebellum in vitro TrkB receptor ligands promote activity-dependent
      inhibitory synaptogenesis of Purkinje cells and also modulate inhibitory synaptic
      function. This mini review examines the roles of TrkB receptor activation by BDNF
      particularly in relation to activity-dependent synaptic plasticity on Purkinje
      cells and recent studies on the acute modulation of GABAergic synapses by BDNF.

PMID- 16997755
TI  - DNER as key molecule for cerebellar maturation.
AB  - Notch signaling plays an important role in the process of cell-fate assignation
      during nervous system development. DNER is a neuron-specific transmembrane
      protein carrying extracellular EGF-like repeats and is expressed in
      somatodendritic regions. In vitro studies demonstrated that DNER mediates Notch
      signaling by cell-cell interaction. In the cerebellum, DNER is abundantly
      expressed in Purkinje cells and moderately in granule cells. DNER-knockout mice
      showed motor discoordination. The mutant cerebellum showed morphological
      impairments of Bergmann glia and multiple innervation between climbing fibers and
      Purkinje cells. Moreover, glutamate clearance at the synapses between parallel
      fibers and Purkinje cells was significantly weakened, and the expression of
      GLAST, a glutamate transporter in Bergmann glia, was reduced in the mutant
      cerebellum. Therefore, DNER contributes to the morphological and functional
      maturation of Bergmann glia via the Notch signaling pathway, and is essential for
      precise cerebellar development.

PMID- 16997756
TI  - Tachykinins and excitotoxicity in cerebellar granule cells.
AB  - The tachykinins represent an important group of neuropeptides that are widely
      distributed both in the central and peripheral nervous system where they perform
      several functions connected with neuronal modulation, often in synergy with
      glutamate excitatory transmission. While a great deal of data is available on
      their distribution and many studies have been performed by molecular,
      biochemical, and immunohistochemical techniques, much less is known about their
      physiological role, in particular in the cerebellum. This review is an attempt to
      summarize the diverse evidence suggesting a role for tachykinins in cerebellar
      granule neurons.

PMID- 16997757
TI  - A case of illusory own-body perceptions after transcranial magnetic stimulation
      of the cerebellum.
AB  - Illusory own-body perceptions are 'body in space' misinterpretations of the brain
      and belong to the class of out-of-body experiences wherein the angular gyrus
      seems importantly implicated. In the present study additional cerebellum
      involvement in illusory own-body perceptions was investigated in a healthy young
      female right-handed volunteer. Transcranial magnetic stimulation (TMS) was
      applied over the cerebellum. Placebo cerebellum TMS and occipital TMS served as
      control conditions. Illusory own-body perceptions accompanied by electric brain
      activity over the somatosensory cortex were only observed after cerebellum TMS.
      The data provide the first evidence that the cerebellum might be involved in a
      neuronal network underlying illusory own-body perceptions.

PMID- 16997759
TI  - Neuroscience in the Nobel perspective.
AB  - The Nobel Prizes for Physiology or Medicine have included a relatively large
      number of awards for work in the neurosciences, or for work construed to have
      made a contribution to neuroscience. These are recognized in this article by
      brief explanations of the particular contribution that warranted this magnificent
      (and munificent) award. The first prizes in neuroscience were awarded five years
      after the initiation of the Nobel Foundation's program. Up to 2005, 28 prizes
      have been awarded for achievements in neuroscience to 52 individuals.

PMID- 16997760
TI  - The impossible interview with the man of the hidden biological structures.
      Interview by Paolo Mazzarello.
AB  - This paper presents an "impossible interview" to Professor Camillo Golgi, placed
      in time in December 1906. The Italian Professor Golgi from Pavia has been awarded
      the Nobel Prize for Physiology or Medicine ex aequo with the Spanish anatomist
      Santiago Ramon y Cajal. Both scientists have obtained the award for their work on
      the anatomy of the nervous system. However, they have opposite views on the
      mechanisms underlying nervous functions. Golgi believes that the axons stained by
      his "black reaction" form a continuous anatomical or functional network along
      which nervous impulses propagate. Ramon y Cajal is the paladin of the neuron
      theory, a hypothesis questioned by Golgi in his Nobel lecture of Tuesday,
      December 11. After the ceremony, an independent journalist has interviewed
      Professor Golgi in the Grand Hotel in Stockholm. Excerpts about his education,
      his main scientific discoveries, and his personal life are here given
      (reconstructing the "impossible interview" on the basis of Golgi's original
      writings).

PMID- 16997761
TI  - The impossible interview with the man of the neuron doctrine. Interview by Edward
      G Jones.
AB  - This paper follows the form of that by Mazzarello that precedes it (Mazzarello,
      2006) and presents an imaginary interview with Santiago Ramon y Cajal in December
      1906. A few days earlier Cajal had been awarded the Nobel Prize for Physiology or
      Medicine, an award that he shared equally with Professor Camillo Golgi. Golgi had
      been recognized for his work as a pioneer into investigations of the nervous
      system, primarily on account of his discovery of the "black reaction" of silver
      chromate impregnation of whole nerve cells and their processes. Cajal had been
      recognized for his implementation of that method and for laying with it the
      foundations of what was to become modern neuroanatomical science. Paradoxically,
      the two awardees had been led by their researches to diametrically opposed views
      of the organization of the nervous system. Golgi believed in a continuous network
      of axons that formed the basis of all the integrative properties of the nervous
      system, while Cajal had provided the information that led to the formulation of
      the neuron doctrine that saw the nervous system as being made up of chains of
      discontinuous cells joined by polarized functional contacts that we now call
      synapses. The paper takes the form of an interview with Professor Cajal in the
      Grand Hotel Stockholm. His responses to questions posed by the imaginary
      interviewer are all taken from Cajal's own writings.

PMID- 16997762
TI  - The 1932 and 1944 Nobel Prizes in physiology or medicine: rewards for ground
      breaking studies in neurophysiology.
AB  - In 1932 Sherrington and Adrian were awarded the Nobel Prize in Physiology or
      Medicine "for their discoveries regarding the functions of neurons" and in 1944
      Erlanger and Gasser were awarded the same prize "for their discoveries relating
      to the highly differentiated functions of single nerve fibres." Sherrington made
      important discoveries on the reflex functions of the spinal cord, formulated the
      concept of the "synapse," defined the principle of the "final common path,"
      studied "reciprocal innervation" and showed that central inhibition was an active
      phenomenon. He distinguished three types of receptors: extero-, intero-, and
      proprioceptive, studied the proprioceptive reflexes in the decerebrate animal and
      mapped their pathways in the spinal cord. Adrian made fundamental discoveries on
      the function of single nerve fibers, developed new techniques for the
      amplification of the weak signals and discovered that increased stimulation
      resulted in increased frequency of the impulses, the amplitude being unaffected.
      Erlanger and Gasser introduced the cathode-ray oscillograph and demonstrated the
      existence of three main groups of nerve fibers, A, B, and C, the conduction
      velocities of which were in approximately linear relationship with the fiber
      diameter, the A-fibers being the fastest and thickest and the C-fibers the
      slowest and having the finest diameter. Together the contributions by the four
      Laureates paved the way to modern neurophysiology.

PMID- 16997763
TI  - Giuseppe Levi: mentor of three Nobel laureates.
AB  - Giuseppe Levi (1872-1965), Professor of Anatomy at the University of Turin, had
      broad research interests and was a pioneer of in vitro studies on cultured cells.
      He provided a number of contributions on the nervous system, especially on the
      plasticity of sensory ganglion cells. An influential and magnetic teacher and
      mentor, he gathered around him a large group of brilliant students. He has the
      peculiar primate to count among his students three Nobel laureates in Physiology
      or Medicine: Salvador Luria, Renato Dulbecco, and Rita Levi-Montalcini. For all
      three of them, the internship in Levi's laboratory provided an exceptional
      initial stimulus. They remained in close contact with each other and with Levi
      even after the 1940s when they migrated to the United States for political and
      racial reasons, engaging in different fields of research. Rita Levi-Montalcini,
      who was awarded the Nobel Prize (1986) for the discovery of Nerve Growth Factor,
      was stimulated and assisted in her work by Giuseppe Levi during the difficult
      years of World War II. With Giuseppe Levi, she pursued early studies on the
      relationships between neural centers and their peripheral target of innervation,
      and she has witnessed in her writings the enthusiasm of her mentor.

PMID- 16997764
TI  - Revisiting the 1981 Nobel Prize to Roger Sperry, David Hubel, and Torsten Wiesel
      on the occasion of the centennial of the Prize to Golgi and Cajal.
AB  - In 1981 the Nobel Prize for Medicine or Physiology was awarded to Roger Sperry
      for his work on the functional specialization of the cerebral hemispheres, and to
      David Hubel and Torsten Wiesel for their work on information processing in the
      visual system. The present paper points to some important links between the work
      of Sperry and that of Hubel and Wiesel and to their influences on neuroscience in
      the best tradition going back to Cajal.

PMID- 16997765
TI  - Nobel laureates at the Stazione Zoologica Anton Dohrn: phenomenology and paths to
      discovery in neuroscience.
AB  - The practice of science usually involves more than a solitary genius in a
      solitary room, coping with the problem of her/his life. From the second half of
      the 19th century onwards, scientific research, especially in the field of the
      Natural Sciences, has grown into a more and more complex practice, which often
      entangles very special needs, in terms of research objects, techniques, sources,
      and perspectives. A few special places, such as the Stazione Zoologica di Napoli,
      have represented in this period the focal points of an ever growing international
      scientific network, promoting independent research, exchange and diffusion of
      novel practices and techniques and unrestricted confrontation. The so-called
      "Naples experience" has been cited by a large number of renowned scientists of
      the last two centuries as a key moment in their scientific life. Here we have
      tried to test it against the experience of three great scientists par excellence,
      i.e. three Nobel laureates (T. H. Morgan, Otto Warburg, J. D. Watson). The
      different experiences they have had at Naples represent, in our view, three
      different moments of the professional life of almost every scientist. Therefore,
      we have chosen to present them as a phenomenology. The final section is dedicated
      to a survey of the Zoological Station's contribution to neurosciences, especially
      to the Naples experience of the Nobel Prize winner Sir Bernard Katz and his
      assistant Ricardo Miledi, between 1965 and 1970. Their work on the squid at
      Naples allowed probing and quantitative refinement of results already obtained on
      different animals and contributed to reinforce the long lasting
      neurophysiological tradition of the institute.

PMID- 16997766
TI  - Eleventh annual meeting of the International Society for the History of the
      Neurosciences, June 21-25, 2006.

PMID- 16997767
TI  - Fundamentals of muscle pain, referred pain, and deep tissue hyperalgesia.

PMID- 16997768
TI  - The C. J. Shanaberger lecture: the evolution of prehospital cardiac care: 1966
      2006 and beyond.
AB  - Prehospital cardiac care began 40 year ago. This lecture reviews the origins and
      evolution of prehospital emergency care for cardiac arrest. Several national and
      international guidelines have defined an evolving standard of care. The most
      recent guidelines, published in 2005, argue for a return to the basics and
      emphasize the importance of CPR and defibrillation. In 40 years we have learned
      much about the epidemiology of cardiac arrest and the factors associated with
      successful resuscitation. Timely CPR and defibrillation remain the cornerstones
      of successful therapy. A new role for EMS personnel may help identify at-risk
      patients and thus prevent future cardiac arrest. A pilot program, know as SPHERE
      (Supporting Public Health with Emergency Responders) is underway in King County,
      Washington. The goal is to identify patients with risk factors of high blood
      pressure or high blood glucose and motivate the patient to seek follow-up care.
      Several intervention strategies are being tested. Since EMS providers see up to
      10% of the population in any given year the chance to identify at-risk patients
      provides a public health opportunity.

PMID- 16997769
TI  - A model protocol for emergency medical services management of asthma
      exacerbations.
AB  - Emergency medical services (EMS) is an important part of the continuum of asthma
      management. The magnitude of the EMS responsibility is very large, with millions
      of patients with asthma treated each year by EMS personnel. In response to
      inconsistencies between the 1997 National Asthma Education and Prevention Program
      asthma guidelines and a variety of existing EMS protocols on the management of
      asthma exacerbations, the Centers for Disease Control and Prevention convened a
      workgroup in 2004 to discuss the various opportunities and challenges ahead. At
      the meeting, and over the ensuing year, the workgroup created a model protocol
      that was derived from the National Asthma Education and Prevention Program
      guidelines. The model protocol is available in both text and algorithm format and
      offers guidance for EMS systems to develop and implement treatment protocols in
      their local areas. The workgroup recommendations emphasize flexibility,
      simplicity, and low-risk practices. By integrating these recommendations into
      existing protocols, we believe that EMS systems could improve prehospital care
      for patients with asthma. Demonstration projects are needed to carefully examine
      the implementation process and the actual impact of the model protocol on various
      outcomes. The workgroup also encourages more research on EMS management of asthma
      exacerbations. In the meantime, improved collaboration between EMS and national
      asthma organizations is an immediate priority and will continue to advance future
      discussions on how to improve asthma management in the prehospital setting. The
      workgroup hopes that state and local EMS systems will see the value of the model
      protocol and encourage its use.

PMID- 16997770
TI  - Effectiveness of prehospital continuous positive airway pressure in the
      management of acute pulmonary edema.
AB  - OBJECTIVE: To compare the effectiveness of continuous positive airway pressure
      (CPAP) with standard pharmacologic treatment in the management of prehospital
      acute pulmonary edema. METHODS: Using a nonrandomized control group design, all
      consecutive patients presenting to two participating emergency medical services
      (EMS) systems with a field impression of acute pulmonary edema between July 1,
      2004, and June 30, 2005, were included in the study. The control EMS system
      patients received standard treatment with oxygen, nitrates, furosemide, morphine,
      and, if indicated, endotracheal intubation. The intervention EMS system patients
      received CPAP via face mask at 10 cm H2O in addition to standard therapy.
      RESULTS: Ninety-five patients received standard therapy, and 120 patients
      received CPAP and standard therapy. Intubation was required in 8.9% of CPAP
      treated patients compared with 25.3% in the control group (p = 0.003), and
      mortality was lower in the CPAP group than in the control group (5.4% vs. 23.2%;
      p = 0.000). When compared with the control group, the CPAP group had more
      improvement in respiratory rate (-4.55 vs. -1.81; p = 0.001), pulse rate (-4.77
      vs. 0.82; p = 0.013), and dyspnea score (-2.11 vs. -1.36; p = 0.008). Using
      logistic regression to control for potential confounders, patients receiving
      standard treatment were more likely to be intubated (odds ratio, 4.04; 95%
      confidence interval, 1.64 to 9.95) and more likely to die (odds ratio, 7.48; 95%
      confidence interval, 1.96 to 28.54) than those receiving standard therapy and
      CPAP. CONCLUSION: The prehospital use of CPAP is feasible, may avert the need for
      endotracheal intubation, and may reduce short-term mortality.

PMID- 16997771
TI  - Influence of ambulance arrival on emergency department time to be seen.
AB  - OBJECTIVES: For a limited number of presenting complaints, arrival by ambulance
      has been shown in some emergency departments to decrease time to be seen by a
      physician. We sought to determine if this time advantage could be demonstrated as
      a national trend over a variety of presenting complaints. METHODS: A secondary
      analysis was performed on the National Hospital Ambulatory Medical Care Survey, a
      national probability sample of emergency department visits. To compare waiting
      times between patients arriving by ambulance and those arriving by walk-in, a
      survival analysis was performed using univariate and multivariate Cox
      proportional hazards models. Primary variables of interest were mode of arrival,
      waiting time to see physician, and immediacy to be seen (triage category). The
      weighted values were utilized to produce national estimates. Patients who left
      without being seen were treated as right censored data. RESULTS: A total of
      61,130 records, weighted to represent 268.3 million emergency department visits
      from 1997 to 2000, were included in the analysis. Patients arrived by ambulance
      in 14.4% of these cases. Median wait time for patients arriving by ambulance was
      14.1 minutes (95% confidence interval [CI], 4.3 to 34.2) as compared with 26.0
      minutes (95% CI, 11.5 to 55.1) for patients who arrived by walk-in. In the
      multivariate analysis, arrival by ambulance offered a 25.0% (95% CI, 19.0% to
      31.6%) time advantage over walk-in and a 40.8% (95% CI, 23.5% to 58.7%) time
      advantage over arrival by public service. CONCLUSIONS: Arrival by ambulance
      offered a time to be seen advantage for a broad range of presenting complaints in
      the National Hospital Ambulatory Medical Care Survey across all triage
      categories.

PMID- 16997772
TI  - Taser use in restraint-related deaths.
AB  - OBJECTIVE: The Taser is an electric weapon capable of releasing significant
      amounts of electricity in rapid pulses, causing uncontrollable muscle
      contraction. Use of this weapon has dramatically increased over the past decade,
      and it is now commonly used by law enforcement officers nationwide. Emergency
      medical services providers are, likewise, seeing more patients who have recently
      been subjected to application of a Taser. We examined the autopsy reports of
      patients who died after application of a Taser in an attempt to identify high
      risk interactions. METHODS: This is a case series of Taser-related deaths.
      Fatalities occurring over four years beginning in January 2001 were identified
      through an Internet search, and autopsy reports were requested. Reports were
      analyzed for patient demographics, preexisting cardiac disease, toxicology,
      evidence of excited delirium, restraint techniques used, and listed cause of
      death. RESULTS: Of 75 cases identified, 37 (49.3%) had autopsy reports available
      for review. All cases involved men, with ages ranging from 18 to 50 years.
      Cardiovascular disease was found in 54.1%. Illegal substance use was found on
      toxicology screening for 78.4%; within that group, 86.2% were found to have been
      using stimulants. A diagnosis of excited delirium was given for 75.7% of the
      cases. Use of a Taser was considered a potential or contributory cause of death
      in 27%. CONCLUSIONS: This is the largest review of Taser-related fatalities
      reported in the medical literature. The findings are consistent with prior
      studies, suggesting a high frequency of restraint-related and excited delirium
      related fatalities.

PMID- 16997773
TI  - A comparative analysis of two external health care disaster responses following
      Hurricane Katrina.
AB  - OBJECTIVE: Hurricane Katrina severely disrupted the health services in the U.S.
      Gulf Coast, necessitating an external health care response. The types and needs
      of patients following such an extensive event have not been well described. The
      objective of this study was to analyze the types of patients treated in two
      temporary clinics and to identify differences between them. METHODS: Two
      temporary sites were established: a disaster medical assistance team-based site
      in Mississippi and a volunteer-based site near New Orleans. Data were abstracted
      from patient charts for the two days of simultaneous operation: September 11 and
      12, 2005. Each patient's age group, disposition, and primary discharge diagnosis
      was categorized and analyzed with descriptive and comparative statistics.
      RESULTS: There were a total of 501 patient encounters. The most common
      presentation overall was for chronic health conditions such as medication refills
      (20.6%), immunizations (11.0%), obtaining community resources (6.0%). and
      management of acute exacerbation of chronic hypertension (4.6%). There were
      important differences; the Mississippi site treated more acute conditions than
      the Louisiana site, including lacerations (13.7% vs. 0%; p < 0.001),
      musculosketal injuries (9.4% vs. 2.6%; p < 0.001), and other nonspecified
      injuries (3.0% vs. 0.4%; p = 0.020). CONCLUSIONS: With extensive damage to a
      health care system, these temporary clinics staffed by out-of-state volunteers
      provided needed health care. The most common health problems were related to
      chronic disease, primary health care, and routine emergency care, not to the
      direct impact of the hurricane. In addition to treating minor injuries, disaster
      planners should prepare to provide primary health care, administer vaccinations,
      and provide missing long-term medications.

PMID- 16997774
TI  - Paramedic self-reported medication errors.
AB  - BACKGROUND: Continuing quality improvement (CQI) reviews reflect that medication
      administration errors occur in the prehospital setting. These include errors
      involving dose, medication, route, concentration, and treatment. METHODS: A
      survey was given to paramedics in San Diego County. The survey tool was
      established based on previous literature reviews and questions developed based on
      previous CQI data. RESULTS: A total of 352 surveys were returned, with the
      paramedics reporting a mean of 8.5 years of field experience. They work an
      average of 11.0 shifts/month with an average shift length of 25.4 hours and 6.7
      calls/shift. Thirty-two responding paramedics (9.1%) reported committing a
      medication error in the past 12 months. Types of errors included dose-related
      errors (63%), protocol errors (33%), wrong route errors (21%), and wrong
      medication errors (4%). Issues identified in contributing to the errors include
      failure to triple check, infrequent use of the medication, dosage calculation
      error, and incorrect dosage given. Fatigue, training, and equipment setup of the
      drug box were not listed as any of the contributing factors. The majority of
      these errors were self-reported to their CQI representative (79.1%), with 8.3%
      reported by the base hospital radio nurse, 8.3% found on chart review, and 4.2%
      noted by the paramedic during the call but never reported. CONCLUSIONS: Nine
      percent of paramedics responding to an anonymous survey reported medication
      errors in the past 12 months, with 4% of these errors never having been reported
      in the CQI process. Additional safeguards must continue to be implemented to
      decrease the incidence of medication errors.

PMID- 16997775
TI  - Midazolam and diazepam for pediatric seizures in the prehospital setting.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy and adverse
      events associated with the use of diazepam and midazolam for the treatment of
      pediatric seizures in the prehospital setting. METHODS: This was a retrospective
      cohort study of all patients younger than 18 years treated for a seizure with a
      benzodiazepine by emergency medical services in Multnomah County, Oregon, from
      1998 to 2001. The emergency medical services system consists of a single private
      advanced life support transporting ambulance service with fire department first
      responders that are all advanced life support capable. The benzodiazepine used
      changed from diazepam to midazolam at the midpoint of this period. The primary
      outcomes were termination of the seizure by arrival to the emergency department
      (ED), recurrence of seizure while in the ED, or the requirement for active airway
      interventions including intubation. The two cohorts were also compared for
      demographics, past history of seizures, long-term use of seizure medications,
      response times, route of administration, use of second doses of benzodiazepines,
      and final disposition. RESULTS: Forty-five patients were treated with diazepam,
      and 48 were treated with midazolam. The two cohorts were comparable except the
      diazepam cohort had a significantly increased proportion of patients with
      previous afebrile seizures (53% vs. 25%; p = 0.005). The midazolam cohort had an
      increased use of nonintravenous route for initial dosing (65% vs. 42%; p = 0.02).
      The two cohorts were equivalent in rates of termination of seizures before to ED
      arrival, recurrence of seizures in the ED, requiring airway support or a second
      dose of benzodiazepine, and admission to the hospital. CONCLUSIONS: Diazepam and
      midazolam appear to be equivalent in treating seizures and causing adverse
      events. Paramedics appear to be administering midazolam intramuscularly more
      often than they use diazepam rectally.

PMID- 16997776
TI  - Naloxone use in a tiered-response emergency medical services system.
AB  - OBJECTIVE: To examine the delivery and effect of naloxone for opioid overdose in
      a tiered-response emergency medical services (EMS) system and to ascertain how
      much time could be saved if the first arriving emergency medical technicians
      (EMTs) could have administered intranasal naloxone. METHODS: This was case series
      of all EMS-treated overdose patients who received naloxone by paramedics in a two
      tiered EMS system during 2004. The system dispatches basic life support-trained
      fire fighter-EMTs and/or advanced life support-trained paramedics depending on
      the severity of cases. Main outcomes were geographic distribution of naloxone
      treated overdose, severity of cases, response to naloxone, and time interval
      between arrival of EMTs and arrival of paramedics at the scene. RESULTS: There
      were 164 patients who received naloxone for suspected overdose. There were 75
      patients (46%) initially unresponsive to painful stimulus. Respiratory rate was
      <10 breaths/min in 79 (48%). Death occurred in 36 (22%) at the scene or during
      transport. A full or partial response to naloxone occurred in 119 (73%).
      Recognized adverse reactions were limited to agitation/combativeness in 25 (15%)
      and emesis in six (4%). Average EMT arrival time was 5.9 minutes. Average
      paramedic arrival time was 11.6 minutes in most cases and 16.1 minutes in 46
      cases (28%) in which paramedics were requested by EMTs at the scene. CONCLUSIONS:
      There is potential for significantly earlier delivery of naloxone to patients in
      opioid overdose if EMTs could deliver intranasal naloxone. A pilot study training
      and authorizing EMTs to administer intranasal naloxone in suspected opioid
      overdose is warranted.

PMID- 16997777
TI  - Drug-assisted effects on protective airway reflexes during out-of-hospital
      endotracheal intubation (preliminary report).
AB  - OBJECTIVE: Out-of-hospital rescuers often use drug-assisted intubation (DAI) to
      facilitate endotracheal intubation (ETI) of nonarrest patients. However, the
      relationship between the ablation of individual protective airway reflexes and
      resulting DAI success has not been defined. We sought to describe the
      relationship between the depression or ablation of protective airway reflexes and
      DAI success. METHODS: We analyzed data from a prospective multicenter trial.
      Rescuers from 42 emergency medical services systems reported clinical ETI data
      using standardized reporting forms. We analyzed the subset receiving sedative
      and/or neuromuscular blocking agents to facilitate ETI. We defined successful ETI
      as intratracheal placement of the endotracheal tube on the last ETI attempt.
      Rescuers reported the presence and ablation of six protective airway reflexes,
      including the presence of a gag, trismus, inadequate relaxation, combativeness,
      laryngospasm, and seizure/myoclonus. We examined the relationship between
      protective reflex ablation and DAI success. RESULTS: Of 1,953 ETIs, 208 (10.7%)
      used DAI (128 sedation only, 80 neuromuscular blocking agents/rapid sequence
      intubation). Successful DAI was associated with ablation of gag reflex (odds
      ratio [OR], 12.7; 95% confidence interval [CI] 3.7 to 46.2), clenched jaw/trismus
      (OR, 54.4; 95% CI, 11.1 to 292.4), inadequate relaxation (OR, 16.3; 95% CI, 3.7
      to 96.4), and combativeness (OR, 10.2; 95% CI, 1.5 to 76.8). Successful DAI was
      associated with the total number of ablated protective reflexes (p < 0.001).
      CONCLUSIONS: The ablation of selected and the total number of protective airway
      reflexes was associated with DAI success. Successful ablation of protective
      airway reflexes should be considered when attempting to characterize DAI
      performance or the effectiveness of specific drug facilitation regimens.

PMID- 16997778
TI  - Path analysis modeling indicates free transport increases ambulance use for minor
      indications.
AB  - INTRODUCTION: Clinically unnecessary ambulance transport is increasing, diverting
      limited resources from patients needing ambulance transport. It was anecdotally
      observed that inappropriate ambulance use increased after abolition of a direct
      patient cost for ambulance transport. HYPOTHESIS: In July 2003, direct patient
      fees were abolished in favor of a universally applied ambulance levy, potentially
      leading to increased ambulance use by patients with low illness acuity and
      admission rates. METHODS: The influence of age, illness acuity, and need for
      admission on ambulance use was assessed for 55,397 emergency department
      attendances in 2002 and 2004. Ambulance users were compared with nonusers in both
      years and attendances for 2002 compared with 2004 using chi-square test for two
      groups. Logistic regression provided a multivariate model leading to ambulance
      use. Path analysis modeling to assess interrelationships between factors
      associated with ambulance use was developed. RESULTS: Ambulance users in both
      years were older, had more acute illness, and had greater need for admission
      compared with nonusers. The odds ratio (OR) of arrival by ambulance in 2004
      compared with 2002 was 1.14 (95% confidence interval, [CI], 1.12 to 1.17). In
      2002, ambulance users were older (OR, 1.42; 95% CI, 1.40 to 1.43), were more
      likely to need admission (OR, 2.28; 95% CI, 2.16 to 2.4) and had higher illness
      acuity (OR, 2.02; 95% CI, 1.94 to 2.09). There was a negative correlation between
      2004 and illness acuity. CONCLUSIONS: Ambulance use increased in 2004 after
      patient transport fees were abolished. Increased use was associated with
      decreased age, clinical acuity, and admission need. Abolishing direct patient
      cost stimulates ambulance use, potentially including inappropriate transport.
      Path analysis to assess the effect of changed funding on ambulance use could be
      used to the influence of other locally relevant factors contributing to ambulance
      use.

PMID- 16997779
TI  - Interfacility transport of patients with decompression illness: literature review
      and consensus statement.
AB  - OBJECTIVE: Decompression illness (DCI) is a potentially lethal complication of
      diving and may occur far from hyperbaric facilities. The need for prompt
      transport to a hyperbaric facility often involves air medical transport, but this
      may exacerbate DCI. The authors reviewed available literature to establish
      evidence-based transport strategies utilizing safe altitudes for patients, with
      DCI. METHODS: MEDLINE, EMBASE, and materials from organizations with expertise in
      diving medicine were searched for the following terms: decompression sickness,
      caisson disease, hyperbaric oxygenation, depth intoxication, or diving. Two
      reviewers independently selected relevant citations involving patients with DCI
      and air medical transport for review and consensus statement development by an
      expert working group. RESULTS: A total of 341 citations were identified, and 53
      unique citations were reviewed. Nine relevant citations were selected for
      consensus statement development. There were no clinical trials or prospective
      cohort studies. Only two retrospective case series, including nine patients,
      specifically examined the effect of altitude on patients with DCI during
      transport. No symptom recurrence occurred when the cabin altitude remained within
      500 feet of ground level. Seven citations were either letters or statements of
      expert opinion, recommending a maximum cabin altitude of 500-1000 feet (152-305
      meters). CONCLUSIONS: The working group identified the paucity of clinical
      studies and evidence-based recommendations for air medical transport of patients
      with DCI. Transport selection should be based on minimizing total transport time
      and, when transporting by air, ensuring that a cabin altitude of the transporting
      vehicle does not exceed 500 feet (152 meters) above the departure point.

PMID- 16997780
TI  - Use of ED diagnosis to determine medical necessity of EMS transports.
AB  - OBJECTIVE: To examine interrater agreement for classifying emergency medical
      services transports as medically unnecessary using emergency department diagnosis
      as the sole determining factor. METHODS: Three emergency physicians and two
      family medicine physicians classified 913 International Classification of
      Diseases, Ninth Revision (ICD-9) codes as medically necessary, unnecessary, or
      uncertain. Overall agreement, interrater agreement, and agreement within 17 major
      disease categories were measured using kappa statistics in SAS. RESULTS:
      Physicians rated between 25% and 65% of diagnoses codes as medically unnecessary.
      Overall agreement was fair (kappa = 0.31). Agreement within specialties was
      higher among family medicine-trained physicians than among emergency physicians
      (kappa = 0.52 and kappa = 0.22, respectively). Agreement across all raters was
      highest for diseases classified as symptoms, signs, and ill-defined conditions
      (kappa = 0.40) and lowest for diseases of the blood and blood-forming organs
      (kappa = -0.17). Agreement was observably better between physicians with more
      experience. CONCLUSIONS: Considerable doubts about the utility of emergency
      department diagnosis as a criterion are raised from study findings. Further
      development of Neely Conference criteria is needed. Priority should be given to
      testing and validation of criteria as well as exploration of differences in
      judgment between specialists representative of the medical director profession.

PMID- 16997781
TI  - Dengue fever with hemorrhagic features in a special forces soldier.
AB  - Military operations are conducted in a variety of settings. Some settings provide
      significant U.S. resources for preventive, primary, urgent, and emergency or
      trauma care. Other operations consist of small numbers of personnel relying on
      limited internal, improvised, and/or host nation resources. Special Forces often
      conduct their missions in rural, austere, and remote settings with a small
      "medical footprint." Often the supported government has difficulty providing
      essential services, including medical care. To address this, U.S. Special Forces
      select and train highly motivated individuals to perform medical duties in an
      exceptionally austere environment devoid of resources. This case highlights those
      services and the medical decision-making process required to provide medical care
      to approach the standard of care in the United States. In this case, the affected
      individual had dengue fever.

PMID- 16997782
TI  - Use of ultrasonography to avoid an unnecessary procedure in the prehospital
      combat environment: a case report.
AB  - The role of ultrasonography in the prehospital combat setting has become a useful
      tool for triage, diagnosis, and treatment. Recent literature has demonstrated
      that ultrasonography has a greater sensitivity and specificity than clinical
      examination and plain radiography for pneumothorax detection in trauma patients,
      particularly small pneumothoraces. This becomes especially critical in austere
      and remote environments. Although many pneumothoraces are initially considered
      non-life-threatening, austere and combat environments possess additional risks of
      limited supplies, multiple casualties, and prolonged evacuation times that may
      potentially increase the morbidity of these injuries. This case report discusses
      the role of ultrasonography in pneumothorax detection in the prehospital combat
      environment.

PMID- 16997784
TI  - A novel inexpensive IV catheterization training model for paramedic students.
AB  - INTRODUCTION: Teaching paramedic students venipuncture and intravenous
      catheterization has traditionally relied on bulky, expensive phlebotomy models. A
      gelatin intravenous model (GIM) costing less than 50 cents is currently being
      used in the training of medical students and interns. The study objective was to
      evaluate paramedic students' perceptions of the GIM as a training tool. METHODS:
      GIMs are created using gelatin, psyllium, Penrose drains, food coloring, salt,
      and water. Penrose drains are filled with artificial blood composed of salt water
      and food coloring. The drains are placed in an aluminum pan with a base of
      hardening gelatin, with half-inch drains at the bottom of the pan and quarter
      inch drains higher up in layers of mixed psyllium and gelatin to simulate deep
      and superficial veins respectively. A convenience, volunteer sample of 14
      paramedic students who previously trained with traditional phlebotomy models each
      made two to five attempts at intravenous insertion using the GIM. Perceptions of
      the GIM were measured using a Likert scale (1, worst rating; 5, best rating).
      Means are reported. RESULTS: Study subjects rated ease of use at 4.17, realism at
      4.07, and effectiveness in learning intravenous insertion at 4.28. GIM as a more
      effective teaching tool than the conventional rubber arm yielded a rating of
      4.14. CONCLUSIONS: This study is limited by a small sample size, and further
      studies evaluating the GIMs construct and content validity are needed. Despite
      these limitations, given the GIMs simplicity and value, paramedic instructors may
      wish to consider implementation of this device in their training programs.

PMID- 16997783
TI  - Skill improvement during emergency response to terrorism training.
AB  - OBJECTIVES: To assess the individual and team skills acquired from an interactive
      training program to prepare emergency personnel to respond to terrorist acts.
      METHODS: We developed a 16-hour, two-day, multimedia- and simulation-enhanced
      course that places learners in realistic situations using the equipment required
      to respond to various chemical, biologic, radiologic, and explosive acts of
      terrorism. Small-group sessions and drills were conducted. Errors in skill
      performance were corrected immediately, and then skills were repeated to achieve
      mastery. Participants included emergency medical technicians, paramedics, nurses,
      and physicians. Team performance was assessed over four successive scenarios
      using a 100-mm visual analog scale. Individual learner skill acquisition was
      assessed with precourse and postcourse evaluation of selected skills in a
      randomized sampling of consenting learners. RESULTS: Nearly all teams achieved
      mastery of the required skills by the second assessment rotation. Individual
      learners demonstrated significant gains in the ability to emergently don personal
      protective equipment and administer a nerve agent antidote kit. CONCLUSIONS: An
      interactive, simulation-enhanced curriculum of terrorism response training for
      emergency responders can produce significant, quantifiable individual and team
      skill gain. Future studies should further address performance benchmarks for
      these newly acquired skills.

PMID- 16997785
TI  - Feasibility of basic emergency medical technicians to perform selected advanced
      life support interventions.
AB  - OBJECTIVE: Emergency medical technician-basic (EMT-B) providers often provide the
      initial care to victims of out-of-hospital cardiac arrest. While automated
      external defibrillators enable EMT-B providers to deliver rescue shocks, patients
      in cardiac arrest may require additional interventions that EMT-B providers may
      not presently deliver. We sought to evaluate the feasibility of training EMT-B
      providers to provide additional cardiac resuscitation procedures using the
      laryngeal mask airway (LMA) and intraosseous (IO) access. METHODS: In this
      prospective observational study, we trained 18 EMT-B providers to use the LMA and
      IO drill (EZ-IO) in a three-hour educational session. Working in two-person
      teams, the rescuers performed a simulated ventricular fibrillation resuscitation.
      We evaluated placement success as well as elapsed time to placement of the LMA
      and EZ-IO. RESULTS: EMT-B providers successfully placed the LMA in 14 of 18
      scenarios (78%; 95% confidence interval, 52% to 94%), with a mean of two attempts
      for placement. Subjects successfully placed the EZ-IO in 17 of 18 scenarios (94%;
      95% confidence interval, 73% to 100%), all on the first attempt. The median time
      to LMA placement following the third shock was 109 seconds (interquartile range,
      58-158) and the median time to EZ-IO placement was 72 seconds (interquartile
      range, 50-93) after LMA placement. CONCLUSIONS: EMT-B providers demonstrated
      moderate success in performing advanced-level cardiac resuscitation
      interventions. These observations suggest potential for expanding the role of
      basic-level rescuers in cardiopulmonary resuscitation.

PMID- 16997788
TI  - Triggering of T cell-mediated immune responses by allogenic tumor cell vaccine in
      patients with oral cancer.
AB  - We investigated the immunomodulatory activity of allogenic whole tumor cell
      vaccine in oral cancer patients in vitro by two-color flow cytometry. Vaccine
      treatment significantly increased the expression of CD69 and HLA-DR in CD3+ T
      cell subsets. The frequency of Interferon-gamma and Interleukin (IL)-2 expressing
      CD4+/CD8+ T-cell subsets was significantly higher with a concomitant reduction in
      IL-4 and IL-10 expressing T-cells in the vaccine treated group as compared with
      the untreated controls. Vaccine treatment significantly increased T-cell receptor
      (TCR), Vbeta3, Vbeta5 and Vbeta8 usage. The results indicate that the allogenic
      whole tumor cell vaccine is able to trigger T-cell mediated immunity in patients
      with intraoral squamous cell carcinoma.

PMID- 16997789
TI  - Design of a new line in treatment of experimental rheumatoid arthritis by
      artesunate.
AB  - This study was aimed to evaluate the therapeutic potency of a new antimalarial
      drug, artesunate, in an experimental model of rheumatoid arthritis. Collagen
      induced arthritis (CIA) was induced in Lewis rats.The intraperitoneally
      administration of artesunate (ARS) and methotrexate (MTX) were started on day 25
      postimmunization and continued until final assessment on day 35. During this
      period, clinical examination was intermittent. 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 ARS and
      MTX were assessed using fibrosarcoma cell line. Our results showed that i.p.
      injection of artesunate 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 reduced inflammatory cells infiltrate in joints of treated rats, and
      tissue edema and bone erosion in the paws were markedly reduced following ARS
      therapy. Moreover, our radiographic results paralleled histological findings.
      Cytotoxicity analysis of ARS showed greater tolerability compared with MTX.
      Treatment with ARS significantly diminished nitric oxide formation in treated
      rats compared with untreated controls. Our findings revealed the therapeutic
      efficacy of artesunate in experimental rheumatoid arthritis compared with a
      choice drug (methotrexate). This result may recommend it as a second-line drug in
      the treatment of rheumatoid arthritis.

PMID- 16997790
TI  - PMA and doxorubicin decrease viability, MTT activity and expression of CD10
      marker on NALM-1 leukemic cells.
AB  - PMA (10, 20 ng/ml) and doxorubicin (5-20 ng/ml) decreased the viability and MTT
      activity of NALM-1 pre-B leukemic cells (3 days' treatment). Further, CD10 was
      downregulated, suggesting that PMA and doxorubicin induced differentiation of
      NALM-1 cells. However, PMA did not alter expression of B cell markers CD20 and of
      mIgM. In contrast to PMA, another differentiation agent ATRA did not alter CD10
      expression on NALM-1 cells but affected viability after 6 days (5, 10 ng/ml). The
      data in this study are the first evidence that PMA and doxorubicin inhibited
      viability and MTT activity and induced partial differentiation, by decreasing
      CD10 on NALM-1 cells.

PMID- 16997791
TI  - Artemisia iwayomogi inhibits immediate-type allergic reaction and inflammatory
      cytokine secretion.
AB  - The immediate-type allergic reaction is involved in many allergic diseases such
      as asthma and allergic rhinitis. The discovery of drugs for the treatment of
      immediate-type allergic diseases is a very important subject in human health. In
      this study, we investigated the effect of Artemisia iwayomogi (AIAE) on mast cell
      mediated allergic reaction and inflammatory cytokine secretion. AIAE inhibited
      compound 48/80-induced systemic reactions in mice. AIAE decreased the passive
      cutaneous anaphylaxis (PCA) reaction activated by antidinitrophenyl (anti-DNP)
      IgE antibody. AIAE dose-dependently reduced histamine release from rat peritoneal
      mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, AIAE
      attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187
      stimulated tumor necrosis factor-alpha and interleukin-6 secretion in human mast
      cells. These results provide evidence that AIAE may be beneficial in the
      treatment of allergic diseases.

PMID- 16997792
TI  - Effect of thalidomide on the expression of TNF-alpha m-RNA and synthesis of TNF
      alpha in cells from leprosy patients with reversal reaction.
AB  - Hypersensitivity reactions called reversal reaction (RR) and erythema nodosum
      leprosum (ENL) occur in leprosy. They are characterized by an increase in tumor
      necrosis factor-alpha (TNF-alpha). Thalidomide is an effective treatment for ENL
      but not RR. Its effectiveness in ENL is attributed to inhibition of TNF-alpha,
      and this does not explain its failure to treat RR. We assessed thalidomide's
      effect on TNF-alpha in RR. Mononuclear cells from RR and non-RR patients and
      healthy individuals were treated with thalidomide and M.leprae (AFB), a cytosol
      fraction of M. leprae or Dharmendra lepromin. Thalidomide suppressed TNF-alpha,
      but when some RR patients' cells were stimulated with AFB, it enhanced TNF-alpha.

PMID- 16997793
TI  - Augmentation of natural killer cell and antibody-dependent cellular cytotoxicity
      in BALB/c mice by sulforaphane, a naturally occurring isothiocyanate from
      broccoli through enhanced production of cytokines IL-2 and IFN-gamma.
AB  - Effect of sulforaphane on cell-mediated immune (CMI) response was studied in
      normal as well as Ehrlich ascites tumor-bearing BALB/c mice. Administration of
      sulforaphane significantly enhanced natural killer (NK) cell activity in both
      normal as well as tumor-bearing animals, and the activity was observed earlier
      than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity
      (ADCC) also was enhanced significantly in both normal as well as tumor-bearing
      animals after sulforaphane administration compared with untreated control tumor
      bearing animals. An early antibody-dependent complement-mediated cytotoxicity
      (ACC) also was observed in sulforaphane-treated normal and tumor-bearing animals.
      Administration of sulforaphane significantly enhanced the production of
      Interleukin-2 and Interferon-gamma in normal as well as tumor-bearing animals. In
      addition, sulforaphane significantly enhanced the proliferation of splenocytes,
      bone marrow cells, and thymocytes by stimulating the mitogenic potential of
      various mitogens such as concanavalin A, phytohaemagglutinin, poke weed mitogen,
      and lipopolysaccharide.

PMID- 16997794
TI  - Effect of atorvastatin on antibody, interleukin-4 and gamma-interferon production
      in mice immunized with egg albumin.
AB  - Three-hydroxy-3-methylglutaryl CoA reductase inhibitors, also known as statins,
      are widely used as the drug of choice for the treatment of hyperlipidemia.
      However, actions beyond that of simply lowering cholesterol levels have been
      reported. This study aims at evaluating the effect of atorvastatin on antibody
      interleukin-4 and gamma-interferon production in mice immunized with egg albumin.
      Antibody levels were determined by an enzyme linked immunosorbent assay and
      cytokine transcripts by reverse transcriptase-polymerase chain reaction. Results
      indicated that repeated daily doses of 40 mg/Kg body weight of atorvastatin
      following immunization suppressed the antibody response in mice to egg albumin.
      Moreover, a decline in interleukin-4 and gamma-interferon transcripts was
      observed.

PMID- 16997795
TI  - In vitro antibacterial activity of bovine dialyzable leukocyte extract.
AB  - The rapidly developing resistance of many infectious pathogenic organisms to
      modern drugs has spurred scientists to search for new sources of antibacterial
      compounds. One potential candidate, bDLE (dialysis at 10 to 12 kDa cut-off) and
      its fractions ("S" and "L" by 3.5 kDa cut-off and I, II, III, and IV by molecular
      exclusion chromatography), was evaluated for antibacterial activity against
      pathogenic bacterial strains (Staphylococcus aureus, Streptococcus pyogenes,
      Lysteria monocytogenes, Escherichia coli, Pseudomonas aeruginosa, and Salmonella
      typhi) using standard antimicrobial assays. A minimum inhibitory concentration
      (MIC) of bDLE and its fractions was determined by agar and broth dilutions
      methods. Only bDLE and its "S" fraction had an effect upon all bacteria evaluated
      (MIC ranging from 0.29 to 0.62 U/ml), and the bactericidal and bacteriostatic
      effects (evaluated by MTT assay) were bacterial species-dependent. These results
      showed a remarkable in vitro antibacterial property of bDLE against several
      pathogenic bacteria.

PMID- 16997796
TI  - Role of protein kinase C in hydroxyapatite- induced phagocytosis by a murine
      macrophage cell line (RAW264.7).
AB  - The role of protein kinase C (PKC) in hydroxyapatite (HA)-induced phagocytosis by
      RAW 264.7 cells was investigated. The cells were incubated with HA particles at
      various incubation time and the levels of PKC activity were determined from the
      cell lysate. To determine the role of PKC, particles were incubated with the
      cells pretreated with the various concentrations of bisindolylmaleimide, a PKC
      inhibitor, and phagocytosis was then assessed at 60 min. Latex beads were used as
      a control. Our results showed that following incubation with HA particles, the
      levels of PKC activity in RAW264.7 cells was highest at 7 min and then decreased
      to reach the baseline levels of the controls at 30 min. Pretreatment of the cells
      with bisindolylmaleimide significantly reduced phagocytosis of HA particles in a
      dose-dependent pattern. The results of our present study suggest therefore that
      ingestion of HA by RAW264.7 cells may depend on PKC activity that may act in the
      early stages of phagocytosis.

PMID- 16997797
TI  - Suppressive effects of mometasone furoate on an antigen-specific IgE antibody
      response and production of IL-4 in mice.
AB  - A nasal formulation of mometasone furoate (MF) is advantageous in avoiding
      systemic activity characteristic of glucocorticoids when it is applied topically.
      To confirm antiallergic effects of this glucocorticoid formulation elaborately,
      we investigated whether the drug can suppress the production of IgE antibodies
      and related cytokines. It we showed that IgE production induced in mice immunized
      via intranasal route was significantly reduced when the mice were administered MF
      intranasally. Further, MF was effective in inhibiting production of type-2 helper
      T cell cytokines in vivo and in vitro. These results provide a
      immunopharmacological basis for clinical efficacy of this drug.

PMID- 16997798
TI  - In vitro effects of benzophenone-2 and octyl-methoxycinnamate on the production
      of interferon-gamma and interleukin-10 by murine splenocytes.
AB  - Chemical ultraviolet light absorbers (UV-filters) are nowadays widely used in
      cosmetic and plastic industry. Recent in vitro and in vivo studies have reported
      that certain chemical UV-filters possess estrogenic activity raising the question
      of whether these compounds are safe to human health. Work on estrogenic effects
      of these compounds, however, has focused mostly on reproductive organs, and as
      the presence of estrogen receptors has been identified in several cells of the
      immune system, UV screens also may have a great impact on immunity. Thus, we have
      studied the in vitro effects of two widely used UV-filters--benzophenone-2 (BP-2)
      and octyl-methoxycinnamate (OMC)--on the production of interferon (IFN)-gamma and
      interleukin (IL)-10, two cytokines representing Th1- and Th2-type response,
      respectively, by activated murine splenocytes. Cells were cultured on 48-well
      plastic plates and stimulated with 12-miristate 13-acetate (PMA) (5 ng/ml) and
      ionomycin (50 ng/ml) in the presence of different concentrations (10-5-10-8M) of
      the studied substances or 17beta-estradiol (E2). After 48 hr incubation the
      supernatants were collected and the levels of IFN-gamma and IL-10 were measured
      using immunoenzymatic assay. Our results show that BP-2 and OMC at high
      concentrations (10-5M) shifted the Th1/Th2 balance toward a Th2 response (lower
      IFN-gamma production and higher IL-10). These effects were comparable to those of
      E2. Our results clearly show that UV-screens at high doses also may possess
      immunomodulatory effects some of which resemble those of E2.

PMID- 16997799
TI  - Allergic reactions to inhalant glucocorticosteroids: a hot topic for
      pneumologists and allergologists.
AB  - Allergic contact dermatitis to topical glucocorticosteroids (GCS) is a delayed
      type cell-mediated hypersensitivity reaction; it is frequently observed in
      dermatological and allergological practice, although its incidence is likely
      underestimated. By contrast, allergic contact sensitization to inhalant GCS is
      virtually unknown to most pneumologists. Here, we review some cases of adverse
      reactions to inhalant GCS in terms of pathogenetic mechanisms, risk factors,
      epidemiology, and allergic cross-sensitivity. In fact, this particular form of
      sensitization to drugs that have a wide spectrum of use in pneumological practice
      deserves more attention than in the past.

PMID- 16997800
TI  - Effects of androgen disruption by DDE on the development and functioning of the
      immune system in Japanese quail.
AB  - We hypothesized that immunosuppression in birds that is caused by exposure to
      antiandrogenic chemicals occurs mainly through disruption of the development of
      the androgen-sensitive avian lymphoid organ, the bursa of Fabricius. Injections
      of 20.0 or 40.0 mug of p,p'-DDE [ethylene, 1,1-dichloro-2,2-bis(p-chlorophenyl)],
      an antiandrogen, were administered at embryonic day 1. Bursas from only chicks
      treated with DDE were larger than, had fewer follicles, and exhibited
      vacuolization within follicles compared with controls; spleens were unaffected.
      No differences in either immune response test were observed. This study
      demonstrates that the bursa may play a role in androgen-active endocrine
      disrupting chemical-induced immunosuppression.

PMID- 16997801
TI  - Elevated reactive oxygen species but not glutathione regulate mercury resistance
      to AML-2/DX100 cells.
AB  - The multidrug resistance-associated protein (MRP1) mediates cellular efflux of
      various xenobiotics and cellular resistance to heavy metals. Previously we
      reported that MRP1 mediates resistance to mercury exposure and possible mechanism
      mediating MRP1 expression after mercury exposure. This study was designed to
      investigate the role of reactive oxygen species (ROS) and glutathione on the
      resistance of AML-2/DX100 cells to mercuric chloride. The MRP1 overexpressing
      cells (AML-2/DX100) cells showed less scavenging activity to ROS induced by
      mercury while no difference in the basal glutathione levels between AML-2/WT and
      AML-2/DX100 cells. Mercury induced the activation of p38 mitogen-activated
      protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) but not c
      jun-N-terminal kinase in AML-2/DX100 cells. The specific inhibitor for p38 MAPK
      and ERK, and antioxidant decreased the production of MRP1 and therefore
      resistance of AML-2/DX100 cells against mercury exposure. These results suggest
      that induction of ROS and downstream p38 MAPK and ERK were involved in the
      resistance of cells to mercury by expression MRP1 in AML-2/DX100 cells.

PMID- 16997802
TI  - Race, pharmacogenomics, and marketing: putting BiDil in context.
AB  - This article endeavors to place into context recent developments surrounding the
      United States Food and Drug Administration recent approval of BiDil (isosorbide
      dinitrate/hydralazine hydrochloride) (NitroMed, Inc., Lexington, MA) as the first
      ever race-specific drug--in this case to treat heart failure in African
      Americans. It focuses in particular on both commercial incentives and statistical
      manipulation of medical data as framing the drive to bring BiDil to market as a
      race-specific drug. In current discourse about pharmacogenomics, targeting a
      racial audience is perceived as necessary because at this point the technology
      and resources do not exist to scan efficiently every individual's genetic
      profile. The article argues that medical researchers may say they are using race
      as a surrogate to target biology in drug development, but corporations are using
      biology as a surrogate to target race in drug marketing. Pharmacogenomics may
      hold great promise, but on our way to that Promised Land, it is imperative to
      review such short cuts with a critical eye.

PMID- 16997805
TI  - Letter to the Editor: End-of-life care and racial disparities: all social and
      health care sectors must respond!

PMID- 16997803
TI  - Ethical environment, healthcare work, and patient outcomes.

PMID- 16997806
TI  - In defense of the PolyHeme trial.

PMID- 16997807
TI  - Innovation in human research protection: the AbioCor artificial heart trial.

PMID- 16997808
TI  - Will bioethics take the life of philosophy?

PMID- 16997809
TI  - Strange bedfellows? Reflections on bioethics' role in disaster response planning.
AB  - This essay considers the potential role of bioethics in disaster response
      planning and preparedness. Bioethicists can make substantial contributions, by
      ensuring that decision-making and distribution of resources during crises is
      carried out in a fair and just manner, as well as by examining the assumptions
      upon which disaster planning are based. Bioethicists should also be aware of
      potential pitfalls of overly-hasty engagement with this new field.

PMID- 16997810
TI  - Taking stem cells seriously.

PMID- 16997811
TI  - Damage compounded: disparities, distrust, and disparate impact in end-of-life
      conflict resolution policies.
AB  - For a little more than a decade, professional organizations and healthcare
      institutions have attempted to develop guidelines and policies to deal with
      seemingly intractable conflicts that arise between clinicians and patients (or
      their proxies) over appropriate use of aggressive life-sustaining therapies in
      the face of low expectations of medical benefit. This article suggests that,
      although such efforts at conflict resolution are commendable on many levels,
      inadequate attention has been given to their potential negative effects upon
      particular groups of patients/proxies. Based on the well-documented tendency
      among many African Americans to prefer more aggressive end-of-life medical
      interventions, it is proposed that the use of institutional policy to break
      decision making impasse in cases for which aggressive treatment is deemed
      "medically inappropriate" will fall disproportionately on that group. Finally, it
      is suggested that the development and application of institutional conflict
      resolution policies should be evaluated in the context of historical and current
      experiences of marginalization and disempowerment, lest such policies exacerbate
      that experience.

PMID- 16997812
TI  - Our cultures, our selves: toward an honest dialogue on race and end-of-life
      decisions.

PMID- 16997813
TI  - Multiculturalism and end-of-life care: the new Israeli law for the terminally ill
      patient.

PMID- 16997814
TI  - Futility--from hospital policies to state laws.

PMID- 16997815
TI  - What we do not know about racial/ethnic discrimination in end-of-life treatment
      decisions.

PMID- 16997816
TI  - Why should we be concerned about disparate impact?

PMID- 16997817
TI  - Erasure of the past: how failure to remember can be a morally blameworthy act.

PMID- 16997818
TI  - Damage compounded or damage lessened? Disparate impact or the compromises of
      multiculturalism?

PMID- 16997819
TI  - Should possible disparities and distrust trump do-no-harm?

PMID- 16997820
TI  - Unequal stakeholders: "For you, it's an academic exercise; for me, it's my life".

PMID- 16997821
TI  - Just end-of-life policies and patient dignity.

PMID- 16997822
TI  - Pernicious encroachment into end-of-life decision making: federal intervention in
      palliative pain treatment.

PMID- 16997823
TI  - How do we avoid compounding the damage?

PMID- 16997824
TI  - Understanding futility: why trust and disparate impact matter as much as what
      works.

PMID- 16997825
TI  - Altruistic discourse in the informed consent process for childhood cancer
      clinical trials.
AB  - Scholars have debated the role that altruistic considerations play--and should
      play--in recruitment and decision-making processes for clinical trials. Little
      empirical data are available to support their various perspectives. We analyzed
      140 audiotaped pediatric informed consent sessions, of which 95 (68%) included at
      least one discussion of how participation in a cancer clinical trial might
      benefit: 1) the pursuit of scientific knowledge generally; 2) other children with
      cancer specifically; and 3) "the future" and other vaguely defined recipients.
      Clinicians initiated most (80%) of these discussions of altruism. The enrollment
      rate of children in the clinical trial was high (83%) overall, but not higher
      among children whose parents were involved in an altruism-oriented discussion.
      These findings suggest that: (1) clinicians invoke a spectrum of altruistic
      considerations rather than a single monothematic notion of altruism, and (2) the
      effect of altruistic considerations on subsequent enrollment decisions is
      marginal. While further research on this topic is warranted, bioethical debate
      should strive to reflect the diversity of altruistic discourse in clinical
      research encounters and to place this discourse in the context of other,
      including nonaltruistic, considerations.

PMID- 16997826
TI  - Altruism and pediatric oncology trials: it does not tip the decision-making
      scales.

PMID- 16997827
TI  - Can children be altruistic research subjects?

PMID- 16997828
TI  - Improving medicine through research and the constitutive nature of altruism.

PMID- 16997829
TI  - The role of altruism in parental decision-making for childhood cancer clinical
      trials--further questions to explore.

PMID- 16997830
TI  - Altruistic discourse and therapeutic misconception in research informed consent.

PMID- 16997831
TI  - Altruistic motives reconsidered.

PMID- 16997835
TI  - A CCAAT/enhancer-binding protein site at -87 is required for the activation of a
      novel murine melanocortin 2-receptor promoter at late stages during adipogenesis.
AB  - The peptide hormone ACTH stimulates lipolysis and suppresses leptin production in
      adipocytes via the G protein-coupled receptor, melanocortin 2 receptor (MC2-R).
      We have shown previously that peroxisome proliferator-activated receptor-gamma2
      is the primary factor responsible for transactivation of the already identified
      murine MC2-R promoter in the differentiating 3T3-L1 adipocyte cell line. In this
      study we show that despite the activity of this promoter being transient during
      differentiation, MC2-R message remains elevated at later time points during
      adipogenesis. Analysis of the late transcripts reveals that they initiate from a
      transcriptional start site in the first intron of the murine MC2-R. The genomic
      sequence upstream of this start site acts as an adipocyte-specific promoter whose
      activation is delayed in differentiation, compared with the upstream promoter. A
      CCAAT/enhancer-binding protein binding site, 87 bp upstream of the
      transcriptional initiation site, is necessary for the activity of this promoter,
      and protein binding analyses reveal that this site is bound by CCAAT/enhancer
      binding protein factors. Real-time PCR analysis of mRNA initiating from the two
      start sites shows that there is a switch in promoter usage from the 5' to the 3'
      promoter around d 5, indicating the complex regulation of the murine MC2-R during
      adipogenesis.

PMID- 16997836
TI  - Aberrant Forkhead box O1 function is associated with impaired hepatic metabolism.
AB  - FoxO1 plays an important role in mediating the effect of insulin on hepatic
      metabolism. Increased FoxO1 activity is associated with reduced ability of
      insulin to regulate hepatic glucose production. However, the underlying mechanism
      and physiology remain unknown. We studied the effect of FoxO1 on the ability of
      insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver
      under fed and fasting conditions. FoxO1 gain of function, as a result of
      adenovirus-mediated or transgenic expression, augmented hepatic gluconeogenesis,
      accompanied by decreased glycogen content and increased fat deposition in liver.
      Mice with excessive FoxO1 activity exhibited impaired glucose tolerance.
      Conversely, FoxO1 loss of function, caused by hepatic production of its dominant
      negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced
      glucose disposal and improved insulin sensitivity in db/db mice. FoxO1 expression
      becomes deregulated, culminating in increased nuclear localization and accounting
      for its increased transcription activity in livers of both high fat-induced obese
      mice and diabetic db/db mice. Increased FoxO1 activity resulted in up-regulation
      of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta,
      fatty acid synthase, and acetyl CoA carboxylase expression, accounting for
      increased hepatic fat infiltration. These data indicate that hepatic FoxO1
      deregulation impairs the ability of insulin to regulate hepatic metabolism,
      contributing to the development of hepatic steatosis and abnormal metabolism in
      diabetes.

PMID- 16997837
TI  - Effect of an intubation dose of rocuronium on Spectral Entropy and Bispectral
      Index responses to laryngoscopy during propofol anaesthesia.
AB  - BACKGROUND: The spectral entropy of the electroencephalogram has been proposed to
      monitor the depth of anaesthesia. State Entropy (SE) reflects the level of
      hypnosis. Response Entropy (RE), computed from electroencephalogram and facial
      muscle activity, reflects the response to nociceptive stimulation. We evaluated
      the effect of rocuronium on Bispectral Index (BIS) and entropy responses to
      laryngoscopy. METHODS: A total of 25 patients were anaesthetized with propofol
      using a target-controlled infusion. At steady state, they randomly received 0.6
      mg kg(-1) rocuronium (R) or saline (S). After 3 min, a 20 s laryngoscopy was
      applied. BIS, RE and SE were recorded continuously and averaged over 1 min during
      baseline, at steady state, 2 min after R or S administration (R/S+2) and 0, 1, 2
      and 3 min after laryngoscopy (L0, L1, L2, L3). RESULTS: At R/S+2, the RE-SE
      gradient was higher in Group S than in Group R. Laryngoscopy provoked an increase
      in BIS, RE and SE. Comparing R/S+2 and L0 values in Groups R and S, BIS increased
      from 43 (6) to 49 (8) and 42 (9) to 51 (15), SE increased from 43 (7) to 50 (8)
      and 41 (10) to 55 (12), and RE increased from 46 (8) to 54 (9) and 47 (12) to 66
      (15), respectively. BIS and SE did not differ between groups. At L0, RE and RE-SE
      were higher in Group S [66 (15) and 11 (4), respectively] than in Group R [54 (9)
      and 4 (2), respectively]. CONCLUSIONS: Rocuronium alters the RE-SE gradient and
      the RE and RE-SE responses to laryngoscopy. Muscle relaxation may confound
      interpretation of entropy monitoring.

PMID- 16997838
TI  - Early transection of a central venous catheter in a sedated ICU patient.
AB  - We report transection and embolization to the heart of a subclavian venous
      catheter in an immobilized and mechanical ventilated patient. The catheter tip
      was retrieved using a percutaneous method via the left femoral vein. Mechanical
      compression of the subclavian venous catheter at the costoclavicular area is
      termed pinch-off syndrome. It can be recognized by intermittent difficulties with
      drug injection, and chest wall swelling at the insertion site. The diagnosis can
      be confirmed by chest radiography with or without contrast administration. A more
      lateral approach of the subclavian vein is advocated to prevent compression.

PMID- 16997839
TI  - Post-conditioning by a short administration of desflurane reduced renal
      reperfusion injury after differing of ischaemia times in rats.
AB  - BACKGROUND: 'Anaesthetic post-conditioning', that is administration of
      anaesthetics during early reperfusion, is known to have positive effects on
      several organs. For the kidney, however, the effects of post-conditioning by
      volatile anaesthetics are not well researched. We examined renal function and
      morphology after post-conditioning by desflurane. METHODS: Anaesthetized rats
      were subjected to 30 or 45 min of renal ischaemia 14 days after contralateral
      nephrectomy. Post-conditioning was achieved by administration of 1 MAC desflurane
      (6.7 vol%) for 15 min during early reperfusion (all groups n=8). Cystatin C
      (CyC), creatinine clearance (Cl(Cr)) and fractional sodium excretion (FE(Na))
      were measured in the awake rats over 3 days. Cell damage was graded from 1 to 4
      in histological sections. Functional variables [mean (SD)] were compared
      statistically by a one-way anova followed by Bonferroni's multiple comparison
      test and histological scores (median and range) by Kruskal-Wallis test followed
      by Dunn's multiple comparison test. RESULTS: Pre-ischaemia function did not
      differ between the groups, but was markedly reduced after ischaemia. After 30 min
      ischaemia, the area under the curve (AUC) for Cl(Cr) was smaller in the
      desflurane than in the control group [21.5 (5.0) vs 31.6 (5.1) ml min(-1) h,
      P<0.05]. After 45 min desflurane reduced the AUC compared with the control group
      for both CyC [15 (4) vs 21 (3) mg litre(-1) h] and FE(Na) [1054 (221) vs 1570
      (572)% h, both P<0.05). Morphological differences were greater between the 30 min
      groups [control: 2.75 (2.0-3.5) vs desflurane: 1.5 (1.0-2.5); P<0.05] than
      between the 45 min groups [control: 3.5 (3.0-4.0) vs desflurane: 3.0 (1.5-4.0)].
      CONCLUSION: Desflurane post-conditioning protects renal function and tissue. This
      protection was greater after the short episode than after the long episode of
      ischaemia.

PMID- 16997840
TI  - Tracheal intubation of morbidly obese patients: LMA CTrach vs direct
      laryngoscopy.
AB  - BACKGROUND: LMA CTrach (CT), a modified version of the intubating LMA Fastrach,
      allows continuous video-endoscopy of the tracheal intubation procedure. We tested
      the hypothesis that the CT is efficient for tracheal intubation of morbidly obese
      patients who are at risk of a difficult airway. METHODS: After Ethics' Committee
      approval, 104 morbidly obese patients (BMI >35 kg m(-2)) scheduled for bariatric
      surgery were included in this prospective study. Patients were randomly assigned
      in two groups: tracheal intubation using direct laryngoscopy (DL) or the CT.
      Induction of anaesthesia was standardized using sufentanil, propofol and
      succinylcholine. Characteristics and consequences of airway management were
      evaluated. RESULTS: Preoperative characteristics of patients and consequences of
      anaesthesia induction on physiological variables were similar in both groups.
      Difficulty in facemask ventilation was similar in both groups. Tracheal
      intubation was successfully carried out with DL and CT. Forty-nine per cent of
      the patients from the CT group required laryngeal mask manipulation (ventilation
      and view optimization) resulting in increased duration of tracheal intubation by
      57 s as compared with DL. Oxygenation was of better quality in the patients
      managed with CT than with DL. Blind tracheal intubation was mandatory in eight
      (17%) patients of the DL group, while tracheal intubation was seen in all
      patients of the CT group. CONCLUSION: We demonstrated that the CT was an
      efficient airway device for ventilation and tracheal intubation in case of a
      difficult airway in morbidly obese patients.

PMID- 16997841
TI  - Adenosine as an adjunct to reperfusion in myocardial infarction.

PMID- 16997842
TI  - Eisenmenger syndrome complicated by pulmonary artery dissection.

PMID- 16997843
TI  - Carriage of OXA-58 but not of OXA-51 beta-lactamase gene correlates with
      carbapenem resistance in Acinetobacter baumannii.

PMID- 16997844
TI  - New antibiotic resistance genes associated with CTX-M plasmids from uropathogenic
      Nigerian Klebsiella pneumoniae.
AB  - OBJECTIVES: To determine antibiotic resistance genes associated with 17 Nigerian
      CTX-M-positive Klebsiella pneumoniae plasmids from patients with community
      acquired urinary tract infections. METHODS: The size and restriction patterns of
      the plasmids were determined, and antibiotic resistance genes were identified
      using DNA-DNA hybridization, PCR assays, hybridization of PCR products with
      internal probes, and sequencing. RESULTS: All CTX-M plasmids were large (58-320
      kb) and carried the following genes: aac(6')-Ib (aminoglycoside resistance) which
      included aac(6')-Ib-cr (aminoglycoside-fluoroquinolone resistance), aadA2
      (aminoglycoside resistance), erm(B) (macrolide-lincosamide-streptogramin B
      resistance), blaTEM-1 (ampicillin resistance), tet(A) (tetracycline resistance),
      sul1 (sulphonamide resistance), dfr (trimethoprim resistance) and intI1, an
      integrase associated with class 1 integrons. Eleven (65%) plasmids carried an
      mph(A) gene (macrolide resistance), seven (41%) plasmids carried a qnrB1 gene
      (low-level quinolone resistance) and four (24%) plasmids carried multiple cat
      genes (chloramphenicol resistance). catA2, catA3 and qnrB1 genes and a 6 kb PstI
      fragment, carrying the blaCTX-M gene, were sequenced. CONCLUSIONS: This is the
      first description of catA2 and catA3 genes in Klebsiella spp. and the first
      description of the erm(B) and floR genes associated with a CTX-M plasmid. This is
      also the first report of qnrB1 and aac(6')-Ib-cr in isolates from Africa and the
      first report of these two genes on the same plasmid.

PMID- 16997845
TI  - Two decades of imipenem therapy.
AB  - Imipenem, the first carbapenem discovered, was developed more than two decades
      ago in response to an unmet need for a highly potent, broad-spectrum
      antimicrobial agent with a strong safety profile. It has since been used to treat
      more than 26 million patients. In an era where antibiotic use has driven
      antibiotic resistance, choosing appropriate initial therapy for serious infection
      is critical. Appropriate antibiotic regimens must cover all likely pathogens, be
      administered promptly at the correct dosage and dosing interval, be well
      tolerated and prevent the emergence of resistance. While imipenem was initially
      reserved for use in intractable, serious infections, the benefits of early
      aggressive therapy are now known, making imipenem a core agent in de-escalation
      therapy due to proven efficacy and safety for indications such as nosocomial
      pneumonia, intra-abdominal infection, sepsis and febrile neutropenia. De
      escalation therapy with an agent such as imipenem minimizes resistance
      development by initiating aggressive initial treatment and then tailoring therapy
      based on patient response and culture results, switching to a less expensive,
      narrower spectrum antibiotic regimen or shortening the duration of therapy.
      Imipenem has maintained sustained clinical efficacy, tolerability and in vitro
      activity against important bacterial pathogens for two decades. We review the
      factors that continue to make imipenem as appropriate an agent for de-escalation
      therapy now as it was 20 years ago.

PMID- 16997846
TI  - Low albumin levels increase endothelial NO production and decrease vascular NO
      sensitivity.
AB  - BACKGROUND: Hypoalbuminaemia is associated with increased risk of cardiovascular
      disease. It is unclear whether endothelial dysfunction is a direct result of low
      albumin or whether it is caused by factors like chronic inflammation or
      dyslipidaemia. In this study, the effect of low albumin concentrations on
      endothelial nitric oxide synthase (eNOS)-dependent NO production was determined
      in vitro and ex vivo. METHODS: eNOS activity, assessed by arginine-citrulline
      conversion, and NO production, determined by 4,5-diaminofluorescein diacetate,
      electron paramagnetic resonance and Griess colorimetry, were measured in cultured
      endothelial cells expressing high levels of eNOS (bEnd.3) after exposure to
      albumin concentrations ranging from 0.5 mmol/l (33 g/l) to 0 mmol/l.
      Analbuminaemic and control rat plasma NO metabolites and aortic eNOS protein mass
      were determined, and aortic endothelium-independent and endothelium-dependent
      vasodilator tone were measured ex vivo under albumin-free conditions. RESULTS: In
      vitro, eNOS activity was significantly increased in the absence of albumin (75 +/
      2 vs 26 +/- 6 pmol/min/mg protein; P < 0.01). Low albumin levels consistently
      increased NO production in endothelial cells. Plasma NO metabolites were
      increased (18.2 +/- 1.9 vs 12.5 +/- 0.8 micromol/l; P < 0.05) and endothelium
      independent relaxation was markedly blunted in analbuminaemic rats, resulting in
      a considerably higher ED50 (80 +/- 2 vs 1.1 +/- 0.2 nmol/l, P < 0.01), while
      endothelium-dependent dilatation was slightly, but significantly, increased.
      Aortic eNOS protein mass was not affected. This implies that in vivo
      hypoalbuminaemia reduces vascular NO sensitivity. CONCLUSION: We show that low
      albumin as such seems to enhance, rather than diminish, eNOS-mediated endothelial
      NO production.

PMID- 16997847
TI  - Common genital complaints in women: the contribution of psychosocial and
      infectious factors in a population-based cohort study in Goa, India.
AB  - BACKGROUND: The genital complaint of abnormal vaginal discharge is common in
      South Asia. We describe the risk factors for the incidence of the complaint in
      women of reproductive age. Method Population-based cohort study in Goa, India.
      Out of 3000 randomly selected women, 2494 women participated. The outcome was an
      incident case of the complaint of abnormal vaginal discharge at 6 months (T1) and
      12 months (T2) review. RESULTS: In total 71 (3.6%, 95% CI 2.8-4.5%) of the 2000
      eligible women reviewed at T1 reported the complaint; and 80 (4.0%, CI 3.2-5.0%)
      of the 1999 women who did not complain of abnormal vaginal discharge at T1
      reported it at T2. Multivariate logistic regression analysis identified the
      following factors as associated with the complaint: younger age (OR 0.26, CI 0.1
      0.5 for women aged 40-49 years compared with women aged 18-24 years); illiteracy
      (OR 1.48, CI 0.9-2.4); religion (Muslim women OR 3.15, CI 1.7-6.0 compared with
      Hindu women); women's concerns regarding their spouse's extramarital
      relationships (OR 3.46, CI 1.2-10.0); current BV infection (OR 1.87, CI 1.2-2.9);
      somatoform complaints (OR 3.30, CI 1.7-6.5 for the highest somatoform score
      quartile compared with the lowest); and depression and anxiety (OR 1.55, CI 0.9
      2.6 for the highest mental health score quartile compared with the lowest).
      CONCLUSIONS: Reproductive and sexual health programmes must strengthen the
      capacity of practitioners to assess and treat bacterial vaginosis and
      psychosocial problems in women with complaints of abnormal vaginal discharge.

PMID- 16997848
TI  - Human telomere biology: pitfalls of moving from the laboratory to epidemiology.
AB  - Remarkable progress has been made during the last 2 decades in understanding
      telomere biology at the molecular and cellular levels. Clinical epidemiology
      research of human telomeres, in contrast, is a discipline just coming into its
      own. The most important observation in studying human telomere biology is that
      telomere length is highly variable among humans. Here we explain some of the
      reasons for this variability and propose several principles that should be
      considered in conducting epidemiological telomere research. Ignoring these
      principles could lead to misleading conclusions.

PMID- 16997849
TI  - Childhood diarrhoea management practices in Bangladesh: private sector dominance
      and continued inequities in care.
AB  - BACKGROUND: Monitoring for disparities in health and services received based upon
      gender, income, and geography should continue as renewed efforts to reduce under
      five mortality are made in response to millennium development goal #4. The
      purpose of this survey was to provide a nationally representative description of
      current childhood diarrhoea management practices and disparities in Bangladesh.
      METHODS: A nationally representative, cross-sectional, cluster-sample survey was
      carried out in randomly selected rural and urban populations across Bangladesh.
      The survey was completed over an 8 month period between November 2003 and June
      2004. RESULTS: A total of 7308 children with a prevalent diarrhoeal illness
      episode within 560 clusters were identified and enrolled in the survey. In 61% of
      the cases help was sought from a health care provider, with over 90% practicing
      in the private sector. Caretaker practice disparities favouring males and higher
      income households were identified. Significant trends (P < 0.001) favouring
      higher income households were found for having sought help from any provider or a
      licensed doctor and for treating their child with oral rehydration solution or an
      antibiotic. Female children in urban households were less likely to be seen by a
      licensed allopath, adj OR 0.73 (95% CI 0.57, 0.94). Among rural households gender
      disparities were limited to females being less likely to receive an antibiotic,
      adj OR 0.74 (95% CI 0.65, 0.86). CONCLUSION: Households seeking help from a
      health provider overwhelmingly utilize the private sector in Bangladesh. Gender
      inequities in the utilization of licensed providers and purchase of antibiotics,
      favouring males were identified. Findings suggest that higher income, urban
      households tend to practice greater gender discrimination. In order to better
      understand health dynamics in urban populations, in particular slum-dwellers,
      there is a need to disaggregate survey data by household location.

PMID- 16997850
TI  - Serum antibody response to periodontal pathogens and herpes simplex virus in
      relation to classic risk factors of cardiovascular disease.
AB  - BACKGROUND: Increasing evidence links chronic infections, especially burden of
      several infections, with increased risk for cardiovascular diseases (CVD). We
      studied joint immune response against two major periodontal pathogens and herpes
      simplex virus (HSV) in relation to established risk factors of CVD. METHODS:
      Serum antibody levels to HSV, Actinobacillus actinomycetemcomitans and
      Porphyromonas gingivalis were determined by ELISA. The study included 1107
      subjects, 734 from Finland and 373 from Russia. RESULTS: Combined antibody
      response to periodontal pathogens was associated inversely (OR, 95% CI) with high
      density lipoprotein (HDL) cholesterol concentration (beta = 0.35; 0.20, 0.60; P <
      0.001) and directly with HSV antibody quartiles: compared with the first
      quartile, ORs (95% CI) for quartiles 2-4 were 1.43 (0.88-2.32), 1.74 (1.07-2.82),
      and 1.89 (1.18-3.02), respectively (P for trend <0.001), after adjusting for age,
      gender, area, education, smoking, BMI, alcohol, triglycerides, and number of
      teeth. In linear regression analysis, the 3-pathogen antibody score (comprising
      antibody levels against periodontal pathogens and HSV) was inversely associated
      with HDL cholesterol concentration (beta = -0.067/1 mmol/l; -0.235, -0.018; P <
      0.05). CONCLUSIONS: HSV infection may promote infection by periodontal pathogens.
      Furthermore, the infectious burden comprising HSV and periodontitis may increase
      the risk for CVD by clearly decreasing HDL cholesterol concentrations.

PMID- 16997851
TI  - Active community surveillance of the impact of different tuberculosis control
      measures, Tiruvallur, South India, 1968-2001.
AB  - BACKGROUND: Tuberculosis is curable, but community surveys documenting
      epidemiological impact of the WHO-recommended DOTS strategy on tuberculosis
      prevalence have not been published. We used active community surveillance to
      compare the impact of DOTS with earlier programmes. METHODS: We conducted
      tuberculosis disease surveys using random cluster sampling of a rural population
      in South India approximately every 2.5 years from 1968 to 1986, using radiography
      as a screening tool for sputum examination. In 1999, DOTS was implemented in the
      area. Prevalence surveys using radiography and symptom screening were conducted
      at the start of DOTS implementation and after 2.5 years. RESULTS: From 1968 to
      1999, culture-positive and smear-positive tuberculosis declined by 2.3 and 2.5%
      per annum compared with 11.9 and 5.6% after DOTS implementation. The 2.5 year
      period of DOTS implementation accounted for one-fourth of the decline in
      prevalence of culture-positive tuberculosis over 33 years. Multivariate analysis
      showed that prevalence of culture-positive tuberculosis decreased substantially
      (10.0% per annum, 95% CI: 2.8-16.6%) owing to DOTS after only slight declines
      related to temporal trends (2.1% annual decline, 95% CI: 1.1-3.2%) and short
      course chemotherapy (1.5% annual decline, 95% CI: -9.7% to 11.5%). Under DOTS,
      the proportion of total cases identified through clinical care increased from 81
      to 92%. CONCLUSIONS: Following DOTS implementation, prevalence of culture
      positive tuberculosis decreased rapidly following a gradual decline for the
      previous 30 years. In the absence of a large HIV epidemic and with relatively low
      levels of rifampicin resistance, DOTS was associated with rapid reduction of
      tuberculosis prevalence.

PMID- 16997852
TI  - Chronic diseases now a leading cause of death in rural India--mortality data from
      the Andhra Pradesh Rural Health Initiative.
AB  - INTRODUCTION: India is undergoing rapid epidemiological transition as a
      consequence of economic and social change. The pattern of mortality is a key
      indicator of the consequent health effects but up-to-date, precise, and reliable
      statistics are few, particularly in rural areas. METHODS: Deaths occurring in 45
      villages (population 180 162) were documented during a 12-month period in 2003-04
      by multipurpose primary healthcare workers trained in the use of a verbal autopsy
      tool. Algorithms were used to define causes of death according to a limited list
      derived from the international classification of disease version 10. Causes were
      assigned by two independent physicians with disagreements resolved by a third.
      RESULTS: A total of 1354 deaths were recorded with verbal autopsies completed for
      98%. A specific underlying cause of death was assigned for 82% of all verbal
      autopsies done. The crude death rate was 7.5/1000 (95% confidence interval, 7.1
      7.9). Diseases of the circulatory system were the leading causes of mortality
      (32%), with similar proportions of deaths attributable to ischaemic heart disease
      and stroke. Second was injury and external causes of mortality (13%) with one
      third of these deaths attributable to deliberate self harm. Third were infectious
      and parasitic diseases (12%). Tuberculosis and intestinal conditions each caused
      one-third of deaths within this category. HIV was assigned as the cause for 2% of
      all deaths. The fourth and fifth leading causes of death were neoplasms (7%) and
      diseases of the respiratory system (5%). CONCLUSION: Non-communicable and chronic
      diseases are the leading causes of death in this part of rural India. The
      observed pattern of death is unlikely to be unique to these villages and provides
      new insight into the rapid progression of epidemiological transition in rural
      India.

PMID- 16997853
TI  - A high-affinity, tryptophan-selective amino acid transport system in human
      macrophages.
AB  - Tryptophan catabolism via the enzyme indoleamine 2,3-dioxygenase (IDO) allows
      human monocyte-derived macrophages (MDM) and other APC to suppress T cell
      proliferation. IDO helps protect murine fetuses from rejection by the maternal
      immune system and can promote tolerance and immunosuppression. For tryptophan to
      be catabolized by IDO, it must first enter the APC via transmembrane transport.
      It has been shown that MDM in vitro readily deplete tryptophan present in the
      extracellular medium to nanomolar levels via IDO activity; yet, no currently
      known amino acid transport system displays high affinity and specificity
      sufficiently to permit efficient uptake of tryptophan at these low
      concentrations. Here, we provide biochemical characterization of a novel
      transport system with nanomolar affinity and high selectivity for tryptophan.
      Tryptophan transport in MDM was predominantly sodium-independent and occurred via
      two distinct systems: one consistent with the known system L transporter and a
      second system with 100-fold higher affinity for tryptophan (Km<300 nM).
      Competition studies showed that the high-affinity system did not correspond to
      any known transporter activity and displayed a marked selectivity for tryptophan
      over other amino acids and tryptophan analogs. This new system was expressed at
      low levels in fresh monocytes but underwent selective induction during MDM
      differentiation. In contrast, resting human T cells expressed only the
      conventional system L. We speculate that the high-affinity, tryptophan-specific
      transport system allows MDM to take up tryptophan efficiently under conditions of
      low substrate concentration, such as may occur during interaction between T cells
      and IDO-expressing APC.

PMID- 16997854
TI  - Mycobacteria-primed macrophages and dendritic cells induce an up-regulation of
      complement C5a anaphylatoxin receptor (CD88) in CD3+ murine T cells.
AB  - Complement C5a anaphylatoxin is a potent activator of macrophages, neutrophils,
      and dendritic cells (DC) and binds the C5a receptor (C5a-R; CD88). Although C5a
      is chemotactic for T cells, expression of C5a-R on murine T cells has been
      disputed. We report here that naive, Con A-activated, and cytokine (IL-12, IL-18)
      stimulated murine CD3+ T cells from three strains of mice [C57Bl/6, B10.nSn
      (C5+/+), B10.on (C5-/-)] lacked C5a-R, as evaluated by immunophenotyping with an
      anti-C5a-R mAb. Ligation of CD3 induced a modest up-regulation with 3% of CD3+ T
      cells expressing cell surface C5a-R. T cells primed by APC differentiate into
      effector T cells. Activation of mycobacteria [bacillus Calmette-Guerin (BCG)]
      sensitized T cells through MHC II and TCR interactions via BCG-infected
      macrophages enhanced the expression of C5a-R with approximately 14% of CD3+ T
      cells positive for C5a-R. Comparable expression was found in C5+/+ as well as C5
      /- strains of mice (14% and 15%, respectively). Furthermore, anti-CD3-activated T
      cells were primed by BCG-infected DC, and a larger proportion of the primed T
      cells expressed C5a-R (30-40%). Finally, mice infected with BCG showed
      significant numbers of CD3+ T cells expressing C5a-R in the spleens during
      infection. As APC, such as macrophages and DC, can secrete C5 and cleave C5 to
      C5a and C5b through a peptidase, we suggest that macrophage and DC-T cell
      interactions can up-regulate C5a-R on T cells through MHC II-TCR and provide a
      C5a peptide for additional local activation of T cells via C5a-R.

PMID- 16997855
TI  - Monocyte/macrophage infiltration in tumors: modulators of angiogenesis.
AB  - The role of a tumor immune infiltrate in cancer progression and metastasis has
      been debated frequently. Although often considered to be associated with improved
      prognosis and leading to the enhanced survival of cancer patients, inflammatory
      cells have also been described to assist the tumor's capabilities to progress,
      proliferate, and metastasize. Tumor-associated macrophages (TAMs), for example,
      have been shown to be symbiotically related to tumor cells: Tumor cells recruit
      TAMs and provide them with survival factors, and TAMs in turn produce a variety
      of angiogenic factors in response to the tumor microenvironment. This review will
      describe the composition of an immune infiltrate in tumors and the angiogenic and
      angiostatic properties of the cells present. Special emphasis will be on the
      angiogenesis-associated activities of TAMs. The development of immunotherapy and
      gene therapy using TAMs to mediate tumor cytotoxicity or to deliver gene
      constructs will be discussed as well. As immunotherapy has so far not been as
      effective as anticipated, a combination therapy in which angiostatic agents are
      used as well is put forward as a novel strategy to treat cancer.

PMID- 16997856
TI  - Cytokine-induced killer T cells kill immature dendritic cells by TCR-independent
      and perforin-dependent mechanisms.
AB  - Cytokine-induced killer (CIK) cells are ex vivo, expanded T cells with proven
      anticancer activity in vitro and in vivo. However, their functional properties
      with the exception of their cancer cell-killing activity are largely unclear.
      Here, we show that CIK T cells recognize dendritic cells (DC), and although
      mature DC (mDC) induce CIK T cells to produce IFN-gamma, immature DC (iDC) are
      killed selectively by them. Moreover, CIK T cell activation by mDC and their
      destruction of iDC are independent of the TCR. The cytotoxicity of CIK T cells to
      iDC is perforin-dependent. Our data have revealed an important regulatory role of
      CIK cells.

PMID- 16997857
TI  - Depletion of MCP-1 increases development of herpetic stromal keratitis by innate
      immune modulation.
AB  - Chemokines are important chemoattractant inflammatory molecules, but their
      interdependent network in disease pathogenesis remains unclear. Studies in mouse
      models have shown that herpetic stromal keratitis (SK) is produced by the
      consequence of a tissue-destructive immunoinflammatory reaction involving herpes
      simplex virus type 1 (HSV) infection. Here we found that ocular HSV infection
      leads to increased expression of monocyte chemoattractant protein-1 (MCP-1), one
      of the major chemoattractants for immune cells that express CCR2, in the SK
      cornea. However, MCP-1 is unlikely to be a chemoattractant for infiltrating Gr
      1(+), CD11b(+) cells in SK, as these cells are found to be CCR2 negative.
      Nevertheless, infection of MCP-1(-/-) mice resulted in more severe SK lesion
      severity compared with WT mice (P<0.01). We demonstrated that the loss of MCP-1
      in the SK cornea caused a significant overexpression of macrophage inflammatory
      protein-2 (MIP-2) (P<0.01) on days 2 and 4 postinfection and increased
      infiltration of inflammatory cells (Gr-1-high and CD11b(+)) expressing CXCR2, a
      receptor for MIP-2, into the cornea. Subsequently, increased infiltration of
      inflammatory cells accelerated by MIP-2 overexpression might result in the high
      production of inflammatory molecules, including vascular endothelial growth
      factor (VEGF) and IL-1beta in SK, as well as CpG oligodeoxynucleotide (ODN)
      implanted eyes of MCP-1(-/-) mice. These results indicate that MCP-1 in the SK
      cornea might regulate the expression of other chemokines, as well as the
      infiltration of inflammatory cells and control development of SK.

PMID- 16997858
TI  - Leukocyte phosphoinositide-3 kinase {gamma} is required for chemokine-induced,
      sustained adhesion under flow in vivo.
AB  - During inflammation, leukocytes roll along the wall of postcapillary venules
      scanning the surface for immobilized CXCL1, a chemokine that triggers firm
      adhesion by activating CXCR2 on the neutrophil. PI-3K are signaling molecules
      important in cellular processes, ranging from cellular differentiation to
      leukocyte migration. PI-3Kgamma can be activated directly by the betagamma dimer
      of heterotrimeric G proteins coupled to CXCR2. Here, we used in vivo and ex vivo
      intravital microscopy models to test the role of PI-3Kgamma in leukocyte arrest.
      PI-3Kgamma null mice showed an 80% decrease in CXCL1-induced leukocyte adhesion
      in venules of the exteriorized mouse cremaster muscle. In wild-type mice, rolling
      leukocytes showed rapid and sustained adhesion, but in PI-3Kgamma(-/-) mice,
      adhesion was not triggered at all or was transient, suggesting that absence of PI
      3Kgamma interferes with integrin bond strengthening. Wild-type mice reconstituted
      with PI-3Kgamma null bone marrow showed a 50% decrease in CXCL1-induced leukocyte
      adhesion. In a blood-perfused micro-flow chamber, leukocytes from PI-3Kgamma(-/-)
      mice showed a defect in adhesion on a P-selectin/ICAM-1/CXCL1 substrate,
      indicating that leukocyte PI-3Kgamma was required for adhesion. The adhesion
      defect in PI-3Kgamma(-/-) mice was as severe as that in mice lacking LFA-1, the
      major integrin responsible for neutrophil adhesion. We conclude that the gamma
      isoform of PI-3K must be functional in leukocytes to allow efficient adhesion
      from rolling in response to chemokine stimulation.

PMID- 16997859
TI  - The maturation potential of NK cell clones toward autologous dendritic cells
      correlates with HMGB1 secretion.
AB  - Interaction of NK cells with autologous immature dendritic cells (iDCs) results
      in reciprocal activation. We have previously reported that NK cells trigger iDC
      to polarize and secrete IL-18; in turn, DC-activated NK cells secrete the nuclear
      protein/proinflammatory cytokine high mobility group box protein 1 (HMGB1), which
      induces DC maturation and prevents DC from lysis. However, activated NK cells can
      also kill iDC. To investigate whether effector and maturative properties may
      coexist or segregate in different NK subsets, human NK cell clones were generated
      and analyzed for their effects on iDC. We found that the ability of different NK
      cell clones to induce iDC maturation is unlinked to their phenotypic and
      cytolytic features but correlates with the relocation of HMGB1 from nucleus to
      cytoplasm. "Maturative" NK cell clones secrete HMGB1 spontaneously. It is
      interesting that secretion is strongly enhanced by engagement of the surface
      molecule NKp30 but only slightly induced by triggering of the activating NK
      receptor CD16. However, culturing freshly isolated NK cells for 1 week with low
      doses of anti-CD16 triggers the relocation of HMGB1 from nucleus to cytoplasm and
      its spontaneous secretion, resulting in a stronger maturation potential of the NK
      cells. Together, our data indicate that NK cells comprise functionally different
      subsets, endowed with different capacities to secrete HMGB1 and to induce
      maturation of autologous iDC. Nonetheless, maturation properties can be modulated
      by different stimuli. This suggests that depending on the environmental stimuli,
      NK/iDC interaction can lead to different outcomes, thus influencing immune
      response.

PMID- 16997860
TI  - Priming by tumor necrosis factor-alpha of human neutrophil NADPH-oxidase activity
      induced by anti-proteinase-3 or anti-myeloperoxidase antibodies.
AB  - Anti-proteinase-3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) antibodies are
      capable of activating human neutrophils primed by TNF-alpha in vitro. We
      described previously the involvement of FcgammaRIIa and beta(2) integrins in this
      neutrophil activation. In the literature, the requirement of TNF priming has been
      attributed to an effect of TNF-alpha on the expression of PR3 or MPO on the cell
      surface. Under our experimental conditions, TNF-alpha (2 ng/ml) increased the
      binding of the antibody against PR3, whereas binding of the antibody against MPO
      could hardly be detected, not even after TNF-alpha treatment. The aim of this
      study was to consider (an)other(s) role(s) for TNF-alpha in facilitating the
      NADPH-oxidase activation by these antibodies. We demonstrate the early
      mobilization of the secretory vesicles as a result of TNF-induced increase in
      intracellular-free calcium ions, the parallel colocalization of gp91(phox), the
      main component of the NADPH oxidase with beta(2) integrins and FcgammaRIIa on the
      neutrophil surface, and the FcgammaRIIa clustering upon TNF priming. TNF-alpha
      also induced redistribution of FcgammaRIIa to the cytoskeleton in a dose- and
      time-dependent manner. Moreover, blocking CD18 MHM23 antibody, cytochalasin B,
      and D609 (an inhibitor of phosphatidylcholine phospholipase C) inhibited this
      redistribution and the respiratory burst in TNF-treated neutrophils exposed to
      anti-PR3 or anti-MPO antibodies. Our results indicate direct effects of TNF-alpha
      in facilitating neutrophil activation by these antibodies and further support the
      importance of cytoskeletal rearrangements in this priming process.

PMID- 16997861
TI  - In vivo regulation of neutrophil apoptosis by C5a during sepsis.
AB  - Delayed neutrophil apoptosis is characteristic of sepsis and may accentuate organ
      injury. It has been shown that PI-3K and MAPK pathways provide survival signaling
      in neutrophils. In this study, we demonstrate that neutrophils isolated from
      septic rats are resistant to apoptosis in comparison with the cells from normal
      animals. In contrast to normal serum, septic sera induced strong phosphorylation
      of AKT and p44/42 in neutrophils obtained from normal rats, resulting in marked
      resistance of these cells to apoptosis. Protection from apoptosis by septic sera
      was abrogated completely by inhibition of PI-3K and partially diminished by MEK
      inhibition. Increased neutrophil survival in septic rats was associated with
      increased levels of Bcl-xL in neutrophils and decreased levels of Bim expression.
      In vivo blockade of C5a in cecal ligation and puncture rats by anti-C5a antibody
      markedly restored the susceptibility of neutrophils to undergo apoptosis. C5a
      activated AKT and p44/42 and also enhanced X-linked inhibitor of apoptosis
      expression in neutrophils. LPS and C5a were able to induce Bcl-xL expression.
      Thus, neutrophil survival signals derived from effects of septic sera could be
      linked to activation of ERK1/2 and PI-3K, increased antiapoptotic protein
      expression, and ultimately, delayed neutrophil apoptosis.

PMID- 16997862
TI  - Endotoxin fever in granulocytopenic rats: evidence that brain cyclooxygenase-2 is
      more important than circulating prostaglandin E(2).
AB  - PGE(2) is a recognized mediator of many fevers, and cyclooxygenase (COX) is the
      major therapeutic target for antipyretic therapy. The source, as well as the site
      of action of PGE(2), as an endogenous pyrogen, is widely accepted as being
      central, but PGE(2) in the circulation, possibly from leukocytes, may also
      contribute to the development of fever. However, bacterial infections are
      important causes of high fever in patients receiving myelosuppressive
      chemotherapy, and such fevers persist despite the use of COX inhibitors. In the
      study reported here, the febrile response to bacterial LPS was measured in rats
      made leukopenic by cyclophosphamide. A striking increase in LPS fever occurred in
      these granulocytopenic rats when compared with febrile responses in normal
      animals. Unlike LPS fever in normal rats, fever in granulocytopenic rats was
      neither accompanied by an increase in blood PGE(2) nor inhibited by ibuprofen.
      Both leukopenic and normal rats showed LPS-induced COX-2-immunoreactivity in
      cells associated with brain blood vessels. Furthermore, LPS induced an increase
      of PGE(2) in cerebrospinal fluid. Induction of COX-2-expression and PGE(2)
      production was inhibited by ibuprofen in normal but not in leukopenic rats.
      Although the results presented are, in part, confirmatory, they add new
      information to this field and open a number of important questions as yet
      unresolved. Overall, the present results indicate that, in contrast to
      immunocompetent rats, leukocytes and/or other mechanisms other than PGE(2) are
      implicated in the mechanisms restricting and reducing the enhanced febrile
      response to endotoxin in immunosuppressed hosts.

PMID- 16997863
TI  - The lipid-associated 3D structure of SPA, a broad-spectrum neuropeptide
      antagonist with anticancer properties.
AB  - [D-Arg(1), D-Trp(5,7,9), Leu(11)] substance P (SPA) belongs to a family of
      peptides including antagonist G and SpD that act as broad-spectrum neuropeptide
      antagonists at several peripheral receptors. The lipid-induced structure of these
      peptides may be important for the receptor interactions of these analogs. Thus we
      describe the tertiary structure of SPA in the presence of sodium dodecylsulfate
      micelles at pH 5.0, and 25 degrees C as determined from two-dimensional (1)H-NMR
      data recorded at 500 MHz. The resulting three-dimensional structure can be
      generally described as two type IV nonstandard turns around Arg(1)*, Pro(2),
      Lys(3), and Pro(4) and Gln(6), Trp(7)*, Phe(8), and Trp(9)* residues,
      respectively, inserted into the interfacial region of the micelles (the asterisks
      denote D-form amino acid). These turns juxtapose the N- and C-termini of SPA and
      may form the basis of this peptide's unique ability to inhibit peptide receptor
      interactions at multiple receptor types.

PMID- 16997864
TI  - Decomposition of protein experimental compressibility into intrinsic and
      hydration shell contributions.
AB  - The experimental determination of protein compressibility reflects both the
      protein intrinsic compressibility and the difference between the compressibility
      of water in the protein hydration shell and bulk water. We use molecular dynamics
      simulations to explore the dependence of the isothermal compressibility of the
      hydration shell surrounding globular proteins on differential contributions from
      charged, polar, and apolar protein-water interfaces. The compressibility of water
      in the protein hydration shell is accounted for by a linear combination of
      contributions from charged, polar, and apolar solvent-accessible surfaces. The
      results provide a formula for the deconvolution of experimental data into
      intrinsic and hydration contributions when a protein of known structure is
      investigated. The physical basis for the model is the variation in water density
      shown by the surface-specific radial distribution functions of water molecules
      around globular proteins. The compressibility of water hydrating charged atoms is
      lower than bulk water compressibility, the compressibility of water hydrating
      apolar atoms is somewhat larger than bulk water compressibility, and the
      compressibility of water around polar atoms is about the same as the
      compressibility of bulk water. We also assess whether hydration water
      compressibility determined from small compound data can be used to estimate the
      compressibility of hydration water surrounding proteins. The results, based on an
      analysis from four dipeptide solutions, indicate that small compound data cannot
      be used directly to estimate the compressibility of hydration water surrounding
      proteins.

PMID- 16997865
TI  - Modulation of HERG gating by a charge cluster in the N-terminal proximal domain.
AB  - Human ether-a-go-go-related gene (HERG) potassium channels contribute to the
      repolarization of the cardiac action potential and display unique gating
      properties with slow activation and fast inactivation kinetics. Deletions in the
      N-terminal 'proximal' domain (residues 135-366) have been shown to induce
      hyperpolarizing shifts in the voltage dependence of activation, suggesting that
      it modulates activation. However, we did not observe a hyperpolarizing shift with
      a subtotal deletion designed to preserve the local charge distribution, and other
      deletions narrowed the region to the KIKER containing sequence 362-372. Replacing
      the positively charged residues of this sequence by negative ones (EIEEE)
      resulted in a -45 mV shift of the voltage dependence of activation. The shifts
      were intermediate for individual charge reversals, whereas E365R resulted in a
      positive shift. Furthermore, the shifts in the voltage dependence were strongly
      correlated with the net charge of the KIKER region. The apparent speeding of the
      activation was attributable to the shifted voltage dependence of activation.
      Additionally, the introduction of negative charges accelerated the intermediate
      voltage-independent forward rate constant. We propose that the modulatory effects
      of the proximal domain on HERG gating are largely electrostatic, localized to the
      charged KIKER sequence.

PMID- 16997866
TI  - Ca2+ selectivity of a chemically modified OmpF with reduced pore volume.
AB  - We studied an E. coli OmpF mutant (LECE) containing both an EEEE-like locus,
      typical of Ca(2+) channels, and an accessible and reactive cysteine. After
      chemical modification with the cysteine-specific, negatively charged (-1e)
      reagents MTSES or glutathione, this LECE mutant was tested for Ca(2+) versus
      alkali metal selectivity. Selectivity was measured by conductance and zero
      current potential. Conductance measurements showed that glutathione-modified LECE
      had reduced conductance at Ca(2+) mole fractions <10(-3). MTSES-modified LECE did
      not. Apparently, the LECE protein is (somehow) a better Ca(2+) chelator after
      modification with the larger glutathione. Zero-current potential measurements
      revealed a Ca(2+) versus monovalent cation selectivity that was highest in the
      presence of Li(+) and lowest in the presence of Cs(+). Our data clearly show that
      after the binding of Ca(2+) the LECE pore (even with the bulky glutathione
      present) is spacious enough to allow monovalent cations to pass. Theoretical
      computations based on density functional theory combined with Poisson-Nernst
      Planck theory and a reduced pore model suggest a functional separation of ionic
      pathways in the pore, one that is specific for small and highly charged ions, and
      one that accepts preferentially large ions, such as Cs(+).

PMID- 16997867
TI  - Modeling leakage kinetics from multilamellar vesicles for membrane permeability
      determination: application to glucose.
AB  - The glucose permeability of bilayers formed from phosphatidylcholine, Brij30, and
      sodium octadecyl sulfate has been determined via an enzymatic reaction. Glucose
      is encapsulated in either uni- or multilamellar vesicles (MLV) and its
      concentration in the dispersion medium is monitored by spectrophotometry analysis
      through the rate of glucose oxidase-catalyzed reaction of glucose oxidation. A
      kinetic model of leakage, taking explicitly into account one, two, or n(w)-walls
      (n(w) >> 1) for the vesicles and assuming an enzymatic Michaelis-Menten behavior,
      is proposed and used to fit the experimental data. The two-wall model was chosen
      to fit experimental data obtained on MLV since an average value of 1.7 bilayers
      was estimated for MLV by cryo-TEM imaging. A permeability value of 5.8 +/- 4.4
      10(-9) cm/s was found. The proposed model is validated by the measurement of the
      bilayer permeability deduced from the modeling of glucose leakage from
      unilamellar vesicles with the same composition. In this latter case, a value of
      8.3 +/- 0.7 10(-9) cm/s is found for the permeability, which is within the error
      bar of the value found with MLV.

PMID- 16997868
TI  - Bipartite expressions for diffusional mass transport in biomembranes.
AB  - Analytical expressions for solute diffusion through a membrane barrier for
      different initial and boundary conditions are available in the literature. The
      three commonest initial and boundary conditions are for a membrane without solute
      respectively immersed in a solution of constant concentration, immersed in such a
      solution for one side but with the other side isolated, and immersed in such a
      solution for one side and with the other side kept at zero concentration. The
      physical quantities for the first two initial and boundary conditions are
      concentration and average concentration (the total solute entering the membrane)
      with amperometric current (flux) and solute that permeates through the membrane
      (charge passed) for the third initial and boundary condition. Expressions for
      these methods in the literature are inconvenient for practical applications
      because of the infinite mathematical series required. An investigation of
      convergence of these expressions was therefore carried out. Simple but accurate
      bipartite expressions for these methods were constructed and provided theoretical
      support for studies on mass transport characterization of biomembranes. As a
      specific application, these expressions enabled a direct fit of the simulated
      observables to experimental values to obtain diffusion coefficients. For these
      initial and boundary conditions and corresponding physical quantities, simple one
      point methods for diffusion coefficient estimation are also suggested. These
      latter diffusion coefficients can be initial values for numerical fit methods.

PMID- 16997869
TI  - Kinetic analysis of amyloid protofibril dissociation and volumetric properties of
      the transition state.
AB  - We present here the first detailed kinetic analysis of the dissociation reaction
      of amyloid protofibrils by utilizing pressure as an accelerator of the reaction.
      The experiment is carried out on an excessively diluted typical protofibril
      solution formed from an intrinsically denatured disulfide-deficient variant of
      hen lysozyme with Trp fluorescence as the reporter in the pressure range 3-400
      MPa. From the analysis of the time-dependent fluorescence decay and the length
      distribution of the protofibrils measured on atomic force microscopy, we conclude
      that the protofibril grows or decays by attachment or detachment of a monomer at
      one end of the protofibril with a monomer dissociation rate independent of the
      length of the fibril. Furthermore, we find that the dissociation reaction is
      strongly dependent on pressure, characterized with a negative activation volume
      DeltaV(odouble dagger) = -50.5 +/- 1.60 ml mol(-1) at 0.1 MPa and with a negative
      activation compressibility Deltakappa(double dagger) = -0.013 +/- 0.001 ml mol(
      1) bar(-1) or -0.9 x 10(-6) ml g(-1) bar(-1). These results indicate that the
      protofibril is a highly compressible high-volume state, but that it becomes less
      compressible and less voluminous in the transition state, most probably due to
      partial hydration of the existing voids. The system eventually reaches the lowest
      volume state with full hydration of the monomer in the dissociated state.

PMID- 16997870
TI  - Antagonistic effects of cofilin, beryllium fluoride complex, and phalloidin on
      subdomain 2 and nucleotide-binding cleft in F-actin.
AB  - Cofilin/ADF, beryllium fluoride complex (BeFx), and phalloidin have opposing
      effects on actin filament structure and dynamics. Cofilin/ADF decreases the
      stability of F-actin by enhancing disorder in subdomain 2, and by severing and
      accelerating the depolymerization of the filament. BeFx and phalloidin stabilize
      the subdomain 2 structure and decrease the critical concentration of actin,
      slowing the dissociation of monomers. Yeast cofilin, unlike some other members of
      the cofilin/ADF family, binds to F-actin in the presence of BeFx; however, the
      rate of its binding is strongly inhibited by BeFx and decreases with increasing
      pH. The inhibition of the cofilin binding rate increases with the time of BeFx
      incubation with F-actin, indicating the existence of two BeFx-F-actin complexes.
      Cofilin dissociates BeFx from the filament, while BeFx does not bind to F-actin
      saturated with cofilin, presumably because of the cofilin-induced changes in the
      nucleotide-binding cleft of F-actin. These changes are apparent from the increase
      in the fluorescence intensity of F-actin bound epsilon-ADP upon cofilin binding
      and a decrease in its accessibility to collisional quenchers. BeFx also affects
      the nucleotide-binding cleft of F-actin, as indicated by an increase in the
      fluorescence intensity of epsilon-ADP-F-actin. Phalloidin and cofilin inhibit,
      but do not exclude each other binding to their complexes with F-actin. Phalloidin
      promotes the dissociation of cofilin from F-actin and slowly reverses the cofilin
      induced disorder in the DNase I binding loop of subdomain 2.

PMID- 16997871
TI  - Coarse-grained molecular dynamics simulations of a rotating bacterial flagellum.
AB  - Many types of bacteria propel themselves using elongated structures known as
      flagella. The bacterial flagellar filament is a relatively simple and well
      studied macromolecular assembly, which assumes different helical shapes when
      rotated in different directions. This polymorphism enables a bacterium to switch
      between running and tumbling modes; however, the mechanism governing the filament
      polymorphism is not completely understood. Here we report a study of the
      bacterial flagellar filament using numerical simulations that employ a novel
      coarse-grained molecular dynamics method. The simulations reveal the dynamics of
      a half-micrometer-long flagellum segment on a timescale of tens of microseconds.
      Depending on the rotation direction, specific modes of filament coiling and
      arrangement of monomers are observed, in qualitative agreement with experimental
      observations of flagellar polymorphism. We find that solvent-protein interactions
      are likely to contribute to the polymorphic helical shapes of the filament.

PMID- 16997872
TI  - Antimicrobial peptides temporins B and L induce formation of tubular lipid
      protrusions from supported phospholipid bilayers.
AB  - The binding of the antimicrobial peptides temporins B and L to supported lipid
      bilayer (SLB) model membranes composed of phosphatidylcholine and
      phosphatidylglycerol (4:1, mol/mol) caused the formation of fibrillar
      protrusions, visible by fluorescent microscopy of both a fluorescent lipid analog
      and a labeled peptide. Multicolor imaging at low peptide-to-lipid ratios (P/L <
      approximately 1:5) revealed an initial in-plane segregation of membrane-bound
      peptide and partial exclusion of lipid from the peptide-enriched areas.
      Subsequently, at higher P/L numerous flexible lipid fibrils were seen growing
      from the areas enriched in lipid. The fibrils have diameters <250 nm and lengths
      of up to approximately 1 mm. Fibril formation reduces the in-plane heterogeneity
      and results in a relatively even redistribution of bound peptide over the planar
      bilayer and the fibrils. Physical properties of the lipid fibrils suggest that
      they have a tubular structure. Our data demonstrate that the peptide-lipid
      interactions alone can provide a driving force for the spontaneous membrane shape
      transformations leading to tubule outgrowth and elongation. Further experiments
      revealed the importance of positive curvature strain in the tubulation process as
      well as the sufficient positive charge on the peptide (>/=+2). The observed
      membrane transformations could provide a simplified in vitro model for
      morphogenesis of intracellular tubular structures and intercellular connections.

PMID- 16997873
TI  - Quantitative morphological analysis reveals ultrastructural diversity of amyloid
      fibrils from alpha-synuclein mutants.
AB  - High resolution atomic force microscopy is a powerful tool to characterize
      nanoscale morphological features of protein amyloid fibrils. Comparison of fibril
      morphological properties between studies has been hampered by differences in
      analysis procedures and measurement error determination used by various authors.
      We describe a fibril morphology analysis method that allows for quantitative
      comparison of features of amyloid fibrils of any amyloidogenic protein measured
      by atomic force microscopy. We have used tapping mode atomic force microscopy in
      liquid to measure the morphology of fibrillar aggregates of human wild-type alpha
      synuclein and the disease-related mutants A30P, E46K, and A53T. Analysis of the
      images shows that fibrillar aggregates formed by E46K alpha-synuclein have a
      smaller diameter (9.0 +/- 0.8 nm) and periodicity (mode at 55 nm) than fibrils of
      wild-type alpha-synuclein (height 10.0 +/- 1.1 nm; periodicity has a mode at 65
      nm). Fibrils of A30P have smaller diameter still (8.1 +/- 1.2 nm) and show a
      variety of periodicities. This quantitative analysis procedure enables comparison
      of the results with existing models for assembly of amyloid fibrils.

PMID- 16997874
TI  - Single nanoparticle photothermal tracking (SNaPT) of 5-nm gold beads in live
      cells.
AB  - Tracking individual nano-objects in live cells during arbitrary long times is a
      ubiquitous need in modern biology. We present here a method for tracking
      individual 5-nm gold nanoparticles on live cells. It relies on the photothermal
      effect and the detection of the Laser Induced Scattering around a NanoAbsorber
      (LISNA). The key point for recording trajectories at video rate is the use of a
      triangulation procedure. The effectiveness of the method is tested against single
      fluorescent molecule tracking in live COS7 cells on subsecond timescales. We
      further demonstrate recordings for several minutes of AMPA receptors trajectories
      on the plasma membrane of live neurons. Single Nanoparticle Photothermal Tracking
      has the unique potential to record arbitrary long trajectory of membrane proteins
      using nonfluorescent nanometer-sized labels.

PMID- 16997875
TI  - Natively folded HypF-N and its early amyloid aggregates interact with
      phospholipid monolayers and destabilize supported phospholipid bilayers.
AB  - Recent data depict membranes as the main sites where proteins/peptides are
      recruited and concentrated, misfold, and nucleate amyloids; at the same time,
      membranes are considered key triggers of amyloid toxicity. The N-terminal domain
      of the prokaryotic hydrogenase maturation factor HypF (HypF-N) in 30%
      trifluoroethanol undergoes a complex path of fibrillation starting with initial 2
      3-nm oligomers and culminating with the appearance of mature fibrils. Oligomers
      are highly cytotoxic and permeabilize lipid membranes, both biological and
      synthetic. In this article, we report an in-depth study aimed at providing
      information on the surface activity of HypF-N and its interaction with synthetic
      membranes of different lipid composition, either in the native conformation or as
      amyloid oligomers or fibrils. Like other amyloidogenic peptides, the natively
      folded HypF-N forms stable films at the air/water interface and inserts into
      synthetic phospholipid bilayers with efficiencies depending on the type of
      phospholipid. In addition, HypF-N prefibrillar aggregates interact with, insert
      into, and disassemble supported phospholipid bilayers similarly to other
      amyloidogenic peptides. These results support the idea that, at least in most
      cases, early amyloid aggregates of different peptides and proteins produce
      similar effects on the integrity of membrane assembly and hence on cell
      viability.

PMID- 16997876
TI  - The origin of long-range attraction between hydrophobes in water.
AB  - When water-coated hydrophobic surfaces meet, direct contacts form between the
      surfaces, driving water out. However, long-range attractive forces first bring
      those surfaces close. This analysis reveals the source and strength of the long
      range attraction between water-coated hydrophobic surfaces. The origin is in the
      polarization field produced by the strong correlation and coupling of the dipoles
      of the water molecules at the surfaces. We show that this polarization field
      gives rise to dipoles on the surface of the hydrophobic solutes that generate
      long-range hydrophobic attractions. Thus, hydrophobic aggregation begins with a
      step in which water-coated nonpolar solutes approach one another due to long
      range electrostatic forces. This precursor regime occurs before the entropy
      increase of releasing the water layers and the short-range van der Waals
      attraction provide the driving force to "dry out" the contact surface. The
      effective force of attraction is derived from basic molecular principles, without
      assumptions of the structure of the hydrophobe-water interaction. The strength of
      this force can be measured directly from atomic force microscopy images of a
      hydrophobic molecule tethered to a surface but extending into water, and another
      hydrophobe attached to an atomic force probe. The phenomenon can be observed in
      the transverse relaxation rates in water proton magnetic resonance as well. The
      results shed light on the way water mediates chemical and biological self
      assembly, a long outstanding problem.

PMID- 16997877
TI  - Mechanical properties of the cell nucleus and the effect of emerin deficiency.
AB  - Nuclear structure and mechanics are gaining recognition as important factors that
      affect gene expression, development, and differentiation in normal function and
      disease, yet the physical mechanisms that govern nuclear mechanical stability
      remain unclear. Here we examined the physical properties of the cell nucleus by
      imaging fluorescently labeled components of the inner nucleus (chromatin and
      nucleoli) and the nuclear envelope (lamins and membranes) in nuclei deformed by
      micropipette aspiration (confocal imaged microdeformation). We investigated
      nuclei, both isolated and in intact, living cells, and found that nuclear volume
      significantly decreased by 60-70% during aspiration. While nuclear membranes
      exhibited blebbing and fluid characteristics during aspiration, the nuclear
      lamina exhibited behavior of a solid-elastic shell. Under large deformations of
      GFP-lamin A-labeled nuclei, we observed a decay of fluorescence intensity into
      the tip of the deformed tongue that we interpreted in terms of nonlinear, two
      dimensional elasticity theory. Here we applied this method to study nuclear
      envelope stability in disease and found that mouse embryo fibroblasts lacking the
      inner nuclear membrane protein, emerin, had a significantly decreased ratio of
      the area expansion to shear moduli (K/mu) compared to wild-type cells (2.1 +/-
      0.2 versus 5.1 +/- 1.3). These data suggest that altered nuclear envelope
      elasticity caused by loss of emerin could contribute to increased nuclear
      fragility in Emery-Dreifuss muscular dystrophy patients with mutations in the
      emerin gene. Based on our experimental results and theoretical considerations, we
      present a model describing how the nucleus is stabilized in the pipette. Such a
      model is essential for interpreting the results of any micropipette study of the
      nucleus and porous materials in general.

PMID- 16997878
TI  - Structure-function analysis of tritrpticin analogs: potential relationships
      between antimicrobial activities, model membrane interactions, and their micelle
      bound NMR structures.
AB  - Tritrpticin is a member of the cathelicidin family of antimicrobial peptides.
      Starting from its native sequence (VRRFPWWWPFLRR), eight synthetic peptide
      analogs were studied to investigate the roles of specific residues in its
      biological and structural properties. This included amidation of the C-terminus
      paired with substitutions of its cationic and Phe residues, as well as the Pro
      residues that are important for its two-turn micelle-bound structure. These
      analogs were determined to have a significant antimicrobial potency. In contrast,
      two other peptide analogs, those with the three Trp residues substituted with
      either Phe or Tyr residues are not highly membrane perturbing, as determined by
      leakage and flip-flop assays using fluorescence spectroscopy. Nevertheless the
      Phe analog has a high activity; this suggests an intracellular mechanism for
      antimicrobial activity that may be part of the overall mechanism of action of
      native tritrpticin as a complement to membrane perturbation. NMR experiments of
      these two Trp-substituted peptides showed the presence of multiple conformers.
      The structures of the six remaining Trp-containing analogs bound to
      dodecylphosphocholine micelles showed major, well-defined conformations. These
      peptides are membrane disruptive and show a wide range in hemolytic activity.
      Their micelle-bound structures either retain the typical turn-turn structure of
      native tritrpticin or have an extended alpha-helix. This work demonstrates that
      closely related antimicrobial peptides can often have remarkably altered
      properties with complex influences on their biological activities.

PMID- 16997879
TI  - In situ scanning probe microscopy studies of tetanus toxin-membrane interactions.
AB  - Despite the considerable information available with regards to the structure of
      the clostridial neurotoxins, and their inherent threat as biological warfare
      agents, the mechanisms underpinning their interactions with and translocation
      through the cell membrane remain poorly understood. We report herein the results
      of an in situ scanning probe microscopy study of the interaction of tetanus toxin
      C-fragment (Tet C) with supported planar lipid bilayers containing the
      ganglioside receptor G(T1b). Our results show that Tet C preferentially binds to
      the surface of fluid phase domains within biphasic membranes containing G(T1b)
      and that with an extended incubation period these interactions lead to dramatic
      changes in the morphology of the lipid bilayer, including the formation of 40-80
      nm diameter circular cavities. Combined atomic force microscopy/total internal
      reflection fluorescence microscopy experiments confirmed the presence of Tet C in
      the membrane after extended incubation. These morphological changes were found to
      be dependent upon the presence of G(T1b) and the solution pH.

PMID- 16997881
TI  - Acinar origin of CFTR-dependent airway submucosal gland fluid secretion.
AB  - Cystic fibrosis (CF) airway disease arises from defective innate defenses,
      especially defective mucus clearance of microorganisms. Airway submucosal glands
      secrete most airway mucus, and CF airway glands do not secrete in response to VIP
      or forskolin. CFTR, the protein that is defective in CF, is expressed in glands,
      but immunocytochemistry finds the highest expression of CFTR in either the
      ciliated ducts or in the acini, depending on the antibodies used. CFTR is
      absolutely required for forskolin-mediated gland secretion; we used this finding
      to localize the origin of forskolin-stimulated, CFTR-dependent gland fluid
      secretion. We tested the hypothesis that secretion to forskolin might originate
      from the gland duct rather than or in addition to the acini. We ligated gland
      ducts at various points, stimulated the glands with forskolin, and monitored the
      regions of the glands that swelled. The results supported an acinar rather than
      ductal origin of secretion. We tracked particles in the mucus using Nomarski time
      lapse imaging; particles originated in the acini and traveled toward the duct
      orifice. Estimated bulk flow accelerated in the acini and mucus tubules,
      consistent with fluid secretion in those regions, but was constant in the
      unbranched duct, consistent with a lack of fluid secretion or absorption by the
      ductal epithelium. We conclude that CFTR-dependent gland fluid secretion
      originates in the serous acini. The failure to observe either secretion or
      absorption from the CFTR and epithelial Na(+) channel (ENaC)-rich ciliated ducts
      is unexplained, but may indicate that this epithelium alters the composition
      rather than the volume of gland mucus.

PMID- 16997880
TI  - Oxygen alters caveolin-1 and nitric oxide synthase-3 functions in ovine fetal and
      neonatal lung microvascular endothelial cells.
AB  - We determined the effect of oxygen [approximately 100 Torr (normoxia) and
      approximately 30-40 Torr (hypoxia)] on functions of endothelial nitric oxide (NO)
      synthase (NOS-3) and its negative regulator caveolin-1 in ovine fetal and
      neonatal lung microvascular endothelial cells (MVECs). Fetal NOS-3 activity,
      measured as NO production with 0.5-0.9 microM 4-amino-5-methylamino-2,7
      difluorofluorescein, was decreased in hypoxia by 14.4% (P < 0.01), inhibitable by
      the NOS inhibitor N-nitro-L-arginine, and dependent on extracellular arginine.
      Caveolar function, assessed as FITC-BSA (160 microg/ml) endocytosis, was
      decreased in hypoxia by 13.5% in fetal and 22.8% in neonatal MVECs (P < 0.01).
      NOS-3 and caveolin-1 were physically associated, as demonstrated by
      coimmunoprecipitation and colocalization, and functionally associated, as shown
      by cross-activation of endocytosis, by their specific antibodies and activation
      of NOS by albumin. Caveolin peptide, containing the sequence for the PKC
      phosphorylation site of caveolin, and caveolin antiserum against the site
      increased NO production and endocytosis by 12.3% (P < 0.05) and 16% (P < 0.05),
      respectively, in normoxia and increased endocytosis by 25% (P < 0.001) in
      hypoxia. PMA decreased NO production in normoxia and hypoxia by 19.32% (P <
      0.001) and 11.8% (P < 0.001) and decreased endocytosis in normoxia by 20.35% (P <
      0.001). PKC kinase activity was oxygen sensitive, and threonine phosphorylation
      was enhanced in hypoxia. Pertussis toxin increased caveolar and NOS functions.
      These data support our hypothesis that increased Po(2) at birth promotes
      dissociation of caveolin-1 and NOS-3, with an increase in their activities, and
      that PKC and an oxygen-sensitive cell surface G protein-coupled receptor regulate
      caveolin-1 and NOS-3 interactions in fetal and neonatal lung MVECs.

PMID- 16997882
TI  - Dissociation of Crk-associated substrate from the vimentin network is regulated
      by p21-activated kinase on ACh activation of airway smooth muscle.
AB  - The intermediate filament protein vimentin has been shown to be required for
      smooth muscle contraction. The adapter protein p130 Crk-associated substrate
      (CAS) participates in the signaling processes that regulate force development in
      smooth muscle. However, the interaction of vimentin filaments with CAS has not
      been well elucidated. In the present study, ACh stimulation of tracheal smooth
      muscle strips increased the ratio of soluble to insoluble vimentin (an index of
      vimentin disassembly) in association with force development. ACh activation also
      induced vimentin phosphorylation at Ser(56) as assessed by immunoblot analysis.
      More importantly, CAS was found in the cytoskeletal vimentin fraction, and the
      amount of CAS in cytoskeletal vimentin was reduced in smooth muscle strips on
      contractile stimulation. CAS redistributed from the myoplasm to the periphery
      during ACh activation of smooth muscle cells. The ACh-elicited decrease in CAS
      distribution in cytoskeletal vimentin was attenuated by the downregulation of p21
      activated kinase (PAK) 1 with antisense oligodeoxynucleotides. Vimentin
      phosphorylation at this residue, the ratio of soluble to insoluble vimentin, and
      active force in smooth muscle strips induced by ACh were also reduced in PAK
      depleted tissues. These results suggest that PAK may regulate CAS release from
      the vimentin intermediate filaments by mediating vimentin phosphorylation at
      Ser(56) and the transition of cytoskeletal vimentin to soluble vimentin. The PAK
      mediated dissociation of CAS from the vimentin network may participate in the
      cellular processes that affect active force development during ACh activation of
      tracheal smooth muscle tissues.

PMID- 16997883
TI  - Role of endogenous TGF-beta in glucocorticoid-induced lung type II cell
      differentiation.
AB  - In the fetal lung, endogenous transforming growth factor (TGF)-beta inhibits
      early morphogenesis and blocks hormone-induced type II cell differentiation. We
      hypothesized that endogenous TGF-beta inhibits type II cell differentiation and
      that the stimulatory effects of glucocorticoids result in part from suppression
      of TGF-beta. Epithelial cells were isolated from human fetal lung and cultured
      under defined conditions with and without dexamethasone plus cAMP to promote type
      II cell differentiation. Control cells produced TGF-beta, which was activated in
      part by alpha(V)beta(6)-integrin. Treatment with dexamethasone, but not cAMP,
      reduced TGF-beta1 and -beta2 transcripts and TGF-beta bioactivity in culture
      medium. To examine the effects of decreased TGF-beta in the absence of
      glucocorticoid, cells were treated with antibodies to TGF-beta and its receptors.
      By real-time RT-PCR, antibody blockade of TGF-beta reduced serpine1, a TGF-beta
      inducible gene, and increased gene expression for sftpa, sftpb, sftpc, and titf1,
      mimicking the response to hormone treatment. By microarray analysis, 29
      additional genes were induced by both TGF-beta antibody and hormone treatment,
      and 20 other genes were repressed by both treatments. For some genes, the fold
      response was comparable for antibody and hormone treatment. We conclude that
      endogenous TGF-beta suppresses expression of surfactant proteins and selected
      other type II cell genes in fetal lung, in part secondary to increased expression
      of titf1, and we propose that the mechanism of glucocorticoid-induced type II
      cell differentiation includes antagonism of TGF-beta gene suppression. Surfactant
      production during fetal development is likely influenced by relative levels of
      TGF-beta and glucocorticoids.

PMID- 16997884
TI  - Type 2 immune response associated with silicosis is not instrumental in the
      development of the disease.
AB  - It has been proposed that the development of lung fibrosis is associated with a T
      helper type 2 response, mainly characterized by IL-4 and IL-13 production. We
      investigated the potential role of type 2 immune polarization in the silicotic
      process and examined the pulmonary response to silica particles in mice
      genetically deficient for IL-4. We found that IL-4(-/-) mice were not protected
      against the development of silicosis, suggesting that IL-4 is not essential for
      the development of this fibrotic disease. By evaluating the intensity of silica
      induced lung fibrosis in mice deficient for IL-4 receptor alpha (IL-4Ralpha), we
      showed that the establishment of pulmonary fibrosis was independent of both IL-4
      and IL-13. Strong impairment of the type 2 immune response (IgG(1)) in the lungs
      of IL-4(-/-) and IL-4Ralpha(-/-) mice did not affect the development of the
      disease. Measurement of IL-13alpha2 receptor expression and IgG(2a), IL-12p70,
      and IFN-gamma levels in silica-treated IL-4(-/-) and IL-4Ralpha(-/-) animals
      showed that the development of silicosis was not related to an IL-13 signaling
      pathway or a switch to a type 1 response in deficient animals. Our data clearly
      indicate that the type 2 immune response associated with silicosis in mice is not
      required for the development of this inflammatory and fibrotic disease.

PMID- 16997885
TI  - Mechanoreceptors and central command.

PMID- 16997886
TI  - A tale of two dogs: analyzing two models of canine ventricular electrophysiology.
AB  - The extensive development of detailed mathematical models of cardiac myocyte
      electrophysiology in recent years has led to a proliferation of models, including
      many that model the same animal species and specific region of the heart and thus
      would be expected to have similar properties. In this paper we review and compare
      two recently developed mathematical models of the electrophysiology of canine
      ventricular myocytes. To clarify their similarities and differences, we also
      present studies using them in a range of preparations from single cells to two
      dimensional tissue. The models are compared with each other and with new and
      previously published experimental results in terms of a number of their
      properties, including action potential morphologies; transmembrane currents
      during normal heart rates and during alternans; alternans onsets, magnitudes, and
      cessations; and reentry dynamics of spiral waves. Action potential applets and
      spiral wave movies for the two canine ventricular models are available online as
      supplemental material. We find a number of differences between the models,
      including their rate dependence, alternans dynamics, and reentry stability, and a
      number of differences compared with experiments. Differences between models of
      the same species and region of the heart are not unique to these canine models.
      Similar differences can be found in the behavior of two models of human
      ventricular myocytes and of human atrial myocytes. We provide several possible
      explanations for the differences observed in models of the same species and
      region of the heart and discuss the implications for the applicability of models
      in addressing questions of mechanism in cardiac electrophysiology.

PMID- 16997887
TI  - Differential responsiveness of RVLM sympathetic premotor neurons to hypoxia in
      rabbits.
AB  - To determine whether differential sympathetic nerve responses to hypoxia are
      explained by opposing effects of hypoxia upon sympathetic premotor neurons in the
      rostral ventrolateral medulla (RVLM), the cardiac sympathetic nerve and the renal
      sympathetic nerve were recorded in anesthetized and vagotomized rabbits. Renal
      sympathetic nerve was activated by the injection of sodium cyanide solution close
      to the bifurcation of the common carotid artery and/or by inhalation of hypoxic
      gas (3% oxygen-97% nitrogen). On the other hand, cardiac sympathetic nerve was
      inhibited by these stimuli. Barosensitive (inhibited by the stimulation of
      baroreceptor afferents) reticulospinal (antidromically activated by the
      stimulation of the spinal cord) neurons in the RVLM were divided into three
      groups according to their responses to hypoxic stimulation: neurons (Type I, n =
      25), the activity of which was inhibited by the injection of sodium cyanide
      solution close to the bifurcation of the common carotid artery and/or by
      inhalation of hypoxic gas, neurons (Type II, n = 99), the activity of which was
      facilitated by the same stimulation, and neurons (Type III, n = 11), the activity
      of which was not changed. These data indicated that the differential responses of
      cardiac and renal sympathetic nerves might be due to opposing effects of hypoxia
      on individual RVLM neurons.

PMID- 16997888
TI  - Smooth muscle cell-specific transcription is regulated by nuclear localization of
      the myocardin-related transcription factors.
AB  - On the basis of our previous studies on RhoA signaling in smooth muscle cells
      (SMC), we hypothesized that RhoA-mediated nuclear translocalization of the
      myocardin-related transcription factors (MRTFs) was important for regulating SMC
      phenotype. MRTF-A protein and MRTF-B message were detected in aortic SMC and in
      many adult mouse organs that contain a large SMC component. Both MRTFs
      upregulated SMC-specific promoter activity as well as endogenous SM22alpha
      expression in multipotential 10T1/2 cells, although to a lesser extent than
      myocardin. We used enhanced green fluorescent protein (EGFP) fusion proteins to
      demonstrate that the myocardin factors have dramatically different localization
      patterns and that the stimulation of SMC-specific transcription by certain RhoA
      dependent agonists was likely mediated by increased nuclear translocation of the
      MRTFs. Importantly, a dominant-negative form of MRTF-A (DeltaB1/B2) that traps
      endogenous MRTFs in the cytoplasm inhibited the SM alpha-actin, SM22alpha, and SM
      myosin heavy chain promoters in SMC and attenuated the effects of sphingosine 1
      phosphate and transforming growth factor (TGF)-beta on SMC-specific
      transcription. Our data confirmed the importance of the NH(2)-terminal RPEL
      domains for regulating MRTF localization, but our analysis of MRTF-A/myocardin
      chimeras and myocardin RPEL2 mutations indicated that the myocardin B1/B2 region
      can override this signal. Gel shift assays demonstrated that myocardin factor
      activity correlated well with ternary complex formation at the SM alpha-actin
      CArGs and that MRTF-serum response factor interactions were partially dependent
      on CArG sequence. Taken together, our results indicate that the MRTFs regulate
      SMC-specific gene expression in at least some SMC subtypes and that regulation of
      MRTF nuclear localization may be important for the effects of selected agonists
      on SMC phenotype.

PMID- 16997889
TI  - Vascular endothelium-derived factors and arterial stiffness in strength- and
      endurance-trained men.
AB  - Arterial stiffness is higher in strength-trained humans and lower in endurance
      trained humans. However, the mechanisms underlying these different adaptations
      are unclear. Vascular endothelium-derived factors, such as endothelin-1 (ET-1)
      and nitric oxide (NO), play an important role in the regulation of vascular
      tonus. We hypothesized that endogenous ET-1 and NO participate in the adaptation
      of arterial stiffness in different types of exercise training. The purpose of
      this study was to investigate plasma ET-1 and NO concentrations and arterial
      stiffness in strength- and endurance-trained men. Young strength-trained athletes
      (SA; n = 11), endurance-trained athletes (EA; n = 12), and sedentary control men
      (C; n = 12) participated in this study. Maximal handgrip strength in SA and
      maximal oxygen uptake in EA were markedly greater than in C. Aortic pulse-wave
      velocity, which is an established index of arterial stiffness, was higher in SA
      and lower in EA than in C. Additionally, we measured systemic arterial compliance
      (SAC) using carotid artery applanation tonometry and Doppler echocardiography,
      because arterial stiffness is a primary determinant of the compliance. SAC was
      lower in SA and higher in EA compared with that in C. Plasma ET-1 concentrations
      were higher in SA compared with C and EA. We did not find significant differences
      in plasma NO concentrations (measured as the stable end product of NO, i.e.,
      nitrite/nitrate). The relationships of plasma ET-1 concentrations to aortic pulse
      wave velocity and SAC were linear. These results suggest that differences in
      endogenous ET-1 may partly participate in the mechanism underlying different
      adaptations of arterial stiffness in strength- and endurance-trained men.

PMID- 16997890
TI  - Salt loading produces severe renal hemodynamic dysfunction independent of
      arterial pressure in spontaneously hypertensive rats.
AB  - We have previously shown that salt excess has adverse cardiac effects in
      spontaneously hypertensive rats (SHR), independent of its increased arterial
      pressure; however, the renal effects have not been reported. In the present study
      we evaluated the role of three levels of salt loading in SHR on renal function,
      systemic and renal hemodynamics, and glomerular dynamics. At 8 wk of age, rats
      were given a 4% (n = 11), 6% (n = 9), or 8% (n = 11) salt-load diet for the
      ensuing 8 wk; control rats (n = 11) received standard chow (0.6% NaCl). Rats had
      weekly 24-h proteinuria and albuminuria quantified. At the end of salt loading,
      all rats had systemic and renal hemodynamics measured; glomerular dynamics were
      specially studied by renal micropuncture in the control, 4% and 6% salt-loaded
      rats. Proteinuria and albuminuria progressively increased by the second week of
      salt loading in the 6% and 8% salt-loaded rats. Mean arterial pressure increased
      minimally, and glomerular filtration rate decreased in all salt-loaded rats. The
      6% and 8% salt-loaded rats demonstrated decreased renal plasma flow and increased
      renal vascular resistance and serum creatinine concentration. Furthermore, 4% and
      6% salt-loaded rats had diminished single-nephron plasma flow and increased
      afferent and efferent arteriolar resistances; glomerular hydrostatic pressure
      also increased in the 6% salt-loaded rats. In conclusion, dietary salt loading as
      low as 4% dramatically deteriorated renal function, renal hemodynamics, and
      glomerular dynamics in SHR independent of a minimal further increase in arterial
      pressure. These findings support the concept of a strong independent causal
      relationship between salt excess and cardiovascular and renal injury.

PMID- 16997891
TI  - H2O2 increases production of constrictor prostaglandins in smooth muscle leading
      to enhanced arteriolar tone in Type 2 diabetic mice.
AB  - Our previous study showed that arteriolar tone is enhanced in Type 2 diabetes
      mellitus (T2-DM) due to an increased level of constrictor prostaglandins. We
      hypothesized that, in mice with T2-DM, hydrogen peroxide (H(2)O(2)) is involved
      in the increased synthesis of constrictor prostaglandins, hence enhanced basal
      tone in skeletal muscle arterioles. Isolated, pressurized gracilis muscle
      arterioles ( approximately 100 microm in diameter) of mice with T2-DM (C57BL/KsJ
      db(-)/db(-)) exhibited greater basal tone to increases in intraluminal pressure
      (20-120 mmHg) than that of control vessels (at 80 mmHg, control: 25 +/- 5%;
      db/db: 34 +/- 4%, P < 0.05), which was reduced back to control level by catalase
      (db/db: 24 +/- 4%). Correspondingly, in carotid arteries of db/db mice, the level
      of dichlorofluorescein-detectable and catalase-sensitive H(2)O(2) was
      significantly greater. In control arterioles, exogenous H(2)O(2) (0.1-100
      micromol/l) elicited dilations (maximum, 58 +/- 10%), whereas in arterioles of
      db/db mice H(2)O(2) caused constrictions (-28 +/- 8%), which were converted to
      dilations (maximum, 16 +/- 5%) by the thromboxane A(2)/prostaglandin H(2) (TP)
      receptor antagonist SQ-29548. In addition, arteriolar constrictions in response
      to the TP receptor agonist U-46619 were not different between the two groups of
      vessels. Endothelium denudation did not significantly affect basal tone and
      H(2)O(2)-induced arteriolar responses in either control or db/db mice. Also, in
      arterioles of db/db mice, but not in controls, 3-nitrotyrosine staining was
      detected in the endothelial layer of vessels. Thus we propose that, in mice with
      T2-DM, arteriolar production of H(2)O(2) is enhanced, which leads to increased
      synthesis of the constrictor prostaglandins thromboxane A(2)/prostaglandin H(2)
      in the smooth muscle cells, which enhance basal arteriolar tone. These
      alterations may contribute to disturbed regulation of skeletal muscle blood flow
      in Type 2 diabetes mellitus.

PMID- 16997892
TI  - Effects of pacemaker currents on creation and modulation of human ventricular
      pacemaker: theoretical study with application to biological pacemaker
      engineering.
AB  - A cardiac biological pacemaker (BP) has been created by suppression of the inward
      rectifier K(+) current (I(K1)) or overexpression of the hyperpolarization
      activated current (I(h)). We theoretically investigated the effects of
      incorporating I(h), T-type Ca(2+) current (I(Ca,T)), sustained inward current
      (I(st)), and/or low-voltage-activated L-type Ca(2+) channel current (I(Ca,LD)) on
      1) creation of BP cells, 2) robustness of BP activity to electrotonic loads of
      nonpacemaking (NP) cells, and 3) BP cell ability to drive NP cells. We used a
      single-cell model for human ventricular myocytes (HVMs) and also coupled-cell
      models composed of BP and NP cells. Bifurcation structures of the model cells
      were explored during changes in conductance of the currents and gap junction.
      Incorporating the pacemaker currents did not yield BP activity in HVM with normal
      I(K1) but increased the critical I(K1) conductance for BP activity to emerge.
      Expressing I(h) appeared to be most helpful in facilitating creation of BP cells
      via I(K1) suppression. In the coupled-cell model, I(st) significantly enlarged
      the gap conductance (G(C)) region where stable BP cell pacemaking and NP cell
      driving occur, reducing the number of BP cells required for robust pacemaking and
      driving. In contrast, I(h) enlarged the G(C) region of pacemaking and driving
      only when I(K1) of the NP cell was relatively low. I(Ca,T) or I(Ca,LD) exerted
      effects similar to those of I(st) but caused shrinkage or irregularity of BP
      oscillations. These findings suggest that expressing I(st) most effectively
      improves the structural stability of BPs to electrotonic loads and the BP ability
      to drive the ventricle.

PMID- 16997893
TI  - Delayed erythropoietin therapy reduces post-MI cardiac remodeling only at a dose
      that mobilizes endothelial progenitor cells.
AB  - We examined the cardiac effects of chronic erythropoietin (EPO) therapy initiated
      7 days after myocardial infarction (MI) in rats. A single high dose of EPO has
      been shown to reduce infarct size by preventing apoptosis when injected
      immediately after myocardial ischemia. The proangiogenic potential of EPO has
      also been reported, but the effects of chronic treatment with standard doses
      after MI are unknown. In this study, rats underwent coronary occlusion followed
      by reperfusion or a sham procedure. Infarcted rats were assigned to one of three
      treatment groups: 1) 0.75 microg/kg darbepoetin (MI+darb 0.75, n = 12); 2) 1.5
      microg/kg darbepoetin (MI+darb 1.5, n = 12); 3) vehicle (MI+PBS, n = 16), once a
      week from day 7 postsurgery. Sham rats received the vehicle alone (n = 10). After
      8 wk of treatment, the animals underwent echocardiography, left ventricular
      pressure-volume measurements, and peripheral blood endothelial progenitor cell
      (EPC) counting. MI size and capillary density in the border zone and the area at
      risk (AAR) were measured postmortem. The AAR was similar in the three MI groups.
      Compared with MI+PBS, the MI+darb 1.5 group showed a reduction in the MI-to-AAR
      ratio (20.8% vs. 38.7%; P < 0.05), as well as significantly reduced left
      ventricle dilatation and improved cardiac function. This reduction in post-MI
      remodeling was accompanied by increased capillary density (P < 0.05) and by a
      higher number of EPC (P < 0.05). Both darbepoetin doses increased the hematocrit,
      whereas MI+darb 0.75 did not increase EPC numbers or capillary density and had no
      functional effect. We found that chronic EPO treatment reduces MI size and
      improves cardiac function only at a dose that induces EPC mobilization in blood
      and that increases capillary density in the infarct border zone.

PMID- 16997894
TI  - Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells.
AB  - Recent reports have demonstrated that erythroid progenitor cells contain and
      secrete various angiogenic cytokines. Here, the impact of erythroid colony
      forming cell (ECFC) implantation on therapeutic angiogenesis was investigated in
      murine models of hindlimb ischemia. During the in vitro differentiation, vascular
      endothelial growth factor (VEGF) secretion by ECFCs was observed from day 3
      (burst-forming unit erythroid cells) to day 10 (erythroblasts). ECFCs from day 5
      to day 7 (colony-forming unit erythroid cells) showed the highest VEGF
      productivity, and day 6 ECFCs were used for the experiments. ECFCs contained
      larger amounts of VEGF and fibroblast growth factor-2 (FGF-2) than peripheral
      blood mononuclear cells (PBMNCs). In tubule formation assays with human umbilical
      vein endothelial cells, ECFCs stimulated 1.5-fold more capillary growth than
      PBMNCs, and this effect was suppressed by antibodies against VEGF and FGF-2.
      Using an immunodeficient hindlimb ischemia model and laser-Doppler imaging, we
      evaluated the limb salvage rate and blood perfusion after intramuscular
      implantation of ECFCs. ECFC implantation increased both the salvage rate (38% vs.
      0%, P < 0.05) and the blood perfusion (82.8% vs. 65.6%, P < 0.01). In addition,
      ECFCs implantation also significantly increased capillaries with recruitment of
      vascular smooth muscle cells and the capillary density was 1.6-fold higher than
      in the control group. Continuous production of human VEGF from ECFCs in the
      skeletal muscle was confirmed at least 7 days after the implantation.
      Implantation of ECFCs promoted angiogenesis in ischemic limbs by supplying
      angiogenic cytokines (VEGF and FGF-2), suggesting a possible novel strategy for
      therapeutic angiogenesis.

PMID- 16997896
TI  - The effects of inspiratory intrathoracic pressure production on the
      cardiovascular response to submaximal exercise in health and chronic heart
      failure.
AB  - We sought to determine whether the normal inspiratory intrathoracic pressures
      (P(ITP)) produced during exercise contribute to the blunted cardiac output and
      locomotor limb blood flow responses observed in chronic heart failure (CHF). Five
      chronically instrumented dogs exercised on a treadmill at 2.5 mile/h at 5% grade
      while healthy or after the induction of tachycardia-induced CHF. We observed
      several key differences in the cardiovascular responses to changes in the
      inspiratory P(ITP) excursion between health and CHF; namely, 1) removing
      approximately 70% of the normally produced inspiratory P(ITP) excursion during
      exercise (with 15 cmH(2)O inspiratory positive pressure ventilation)
      significantly reduced stroke volume (SV) in healthy animals by 5 +/- 2% (P <
      0.05) but significantly increased SV and cardiac output (Q(TOT)) in animals with
      CHF by 5 +/- 1% (P < 0.05); 2) doubling the magnitude of the inspiratory P(ITP)
      excursion had no effect on SV or Q(TOT) in healthy animals but significantly
      reduced steady-state Q(TOT) and SV in animals with CHF by -4 +/- 3% and -10 +/-
      3%, respectively; 3) removing the majority of the normally produced inspiratory
      P(ITP) excursion had no effect on blood flow distribution in healthy animals but
      increased hindlimb blood flow (9 +/- 3%, P < 0.05) out of proportion to the
      increases in Q(TOT); and 4) the only similarity between healthy and CHF animals
      was that increasing the inspiratory P(ITP) excursion significantly reduced steady
      state locomotor limb blood flow by 5 +/- 2% and 6 +/- 3%, respectively (P < 0.05
      for both). We conclude that 1) the normally produced inspiratory P(ITP)
      excursions are required for a maximal SV response to submaximal exercise in
      healthy animals but detrimental to the SV and Q(TOT) responses to submaximal
      exercise in CHF, 2) the respiratory muscle ergoreflex tonically restrains
      locomotor limb blood flow during submaximal exercise in CHF, and 3) excessive
      inspiratory muscle work further compromises cardiac function and blood flow
      distribution in both health and CHF.

PMID- 16997895
TI  - Pharmacogenetics and anti-arrhythmic drug therapy: a theoretical investigation.
AB  - Pharmacological management of cardiac arrhythmias has been a long and widely
      sought goal. One of the difficulties in treating arrhythmia stems, in part, from
      incomplete understanding of the mechanisms of drug block and how intrinsic
      properties of channel gating affect drug access, binding affinity, and unblock.
      In the last decade, a plethora of genetic information has revealed that genetics
      may play a critical role in determining arrhythmia susceptibility and in efficacy
      of pharmacological therapy. In this context, we present a theoretical approach
      for investigating effects of drug-channel interaction. We use as an example open
      channel or inactivated-channel block by the local anesthetics mexiletine and
      lidocaine, respectively, of normal and DeltaKPQ mutant Na(+) channels associated
      with the long-QT syndrome type 3. Results show how kinetic properties of channel
      gating, which are affected by mutations, are important determinants of drug
      efficacy. Investigations of Na(+) channel blockade are conducted at multiple
      scales (single channel and macroscopic current) and, importantly, during the
      cardiac action potential (AP). Our findings suggest that channel mean open time
      is a primary determinant of open state blocker efficacy. Channels that remain in
      the open state longer, such as the DeltaKPQ mutant channels in the abnormal burst
      mode, are blocked preferentially by low mexiletine concentrations. AP simulations
      confirm that a low dose of mexiletine can remove early afterdepolarizations and
      restore normal repolarization without affecting the AP upstroke. The simulations
      also suggest that inactivation state block by lidocaine is less effective in
      restoring normal repolarization and adversely suppresses peak Na(+) current.

PMID- 16997897
TI  - Case-control study of postmenopausal hormone replacement therapy and endometrial
      cancer.
AB  - This study evaluated recent inconsistent findings that adding progestins to
      postmenopausal estrogen replacement therapy protects against endometrial cancer.
      Using a population-based case-control study, the authors compared 511 endometrial
      cancer cases aged 50-79 years in the Philadelphia, Pennsylvania, region during
      1999-2002 with 1,412 random-digit-dialing controls regarding postmenopausal
      hormone replacement therapy (HRT) use. Telephone interviews were performed with
      memory aids mailed in advance. An increased risk of endometrial cancer was
      observed among postmenopausal women using only unopposed estrogen for 3 or more
      years, compared with women who never used HRT (adjusted odds ratio = 3.4, 95%
      confidence interval (CI): 1.4, 8.3). Using combination HRT (of any duration) was
      associated with a substantial reduction in risk (odds ratio = 0.8, 95% CI: 0.6,
      1.1). Comparing women using only combined estrogen and progestin for 3 or more
      years with women using only unopposed estrogen for 3 or more years, the authors
      found that the adjusted odds ratio was 0.2 (95% CI: 0.1, 0.6). Long-term use of
      unopposed estrogen is associated with increased risk for endometrial cancer,
      whereas combined estrogen plus progestin hormone therapy is not. Thus, if HRT is
      to be used in women with an intact uterus, this study confirms the benefit of
      adding progestins to the regimen.

PMID- 16997898
TI  - Predictors of condom use among sexually active persons involved in compulsory
      national service in Ibadan, Nigeria.
AB  - Migration is known to increase the risk of heterosexual transmission of human
      immunodeficiency virus (HIV) in sub-Saharan Africa, but little attention has been
      paid to fresh graduates of tertiary institutions who are on migration for
      compulsory national assignment in Nigeria. In July and August 2004, a survey was
      conducted on sexually active men (n = 344) and women (n = 373) to investigate
      determinants of condom use during national service. Sixty-eight percent of men
      and 41% of women reported condom use at last intercourse before the survey. For
      both men and women, condom use was common if they had one or more regular sex
      partners and if they were purchasing condoms. In addition, women's condom use was
      predicted by being single and having intention to use condoms in next
      intercourse. The findings further showed that there was high risk of HIV
      transmission in the sample population as consistent condom use was 15% for men
      and 4% for women. Twelve percent of men and 8% of women reported STI diagnoses in
      the last 12 months before the survey. Four percent of men and 2% of women
      reported they already had HIV diagnoses. Only 1% of men and 2% of women reported
      they would receive voluntary HIV test if offered free by the government. The
      study findings suggest the need to extend the existing condom social marketing
      services in the country to the youth on national service and promote condom
      education messages among them prior to commencing national service.

PMID- 16997899
TI  - Metabolism of gamma-aminobutyric acid during cold acclimation and freezing and
      its relationship to frost tolerance in barley and wheat.
AB  - Amino acid homeostasis was investigated in frost-resistant barley seedlings under
      either cold- or freezing-stress conditions. Total free amino acid content varied
      only slightly, but a substantial conversion of glutamate to gamma-aminobutyric
      acid (GABA) was found that was proportional to the severity of the stress. Cold
      acclimation caused a significant increase in amino acid pools, and induced the
      expression of the GABA-shunt genes. As a consequence, GABA accumulated to a
      higher extent during the subsequent exposure to lower temperature. A different
      picture was obtained with a frost-sensitive genotype, in which glutamate
      decarboxylation occurred during the stress as well, but the activation of the
      GABA shunt seemed not to take place, and free glutamate was almost depleted.
      Analogous results were found in frost-resistant and frost-sensitive wheat
      cultivars. Feeding non-hardened plants with exogenous glutamate resulted in
      increased GABA accumulation under low temperature. The possibility that glutamate
      decarboxylation and GABA metabolism would play a role in frost tolerance is
      discussed.

PMID- 16997900
TI  - Effect of activase level and isoform on the thermotolerance of photosynthesis in
      Arabidopsis.
AB  - Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) activation decreases
      under moderate heat stress. This decrease is caused by an impairment of activase
      function, which is exacerbated by faster rates of Rubisco deactivation at
      elevated temperatures. To determine if stromal oxidation causes inhibition of
      activase, transgenic Arabidopsis plants expressing suboptimal amounts of either
      the redox-regulated 46 kDa alpha- or non-redox regulated 43 kDa beta-isoform of
      activase were examined. Photosynthesis, as measured by gas exchange and
      chlorophyll fluorescence, and Rubisco activation were inhibited to a much greater
      extent by moderately high temperatures in the two transgenic lines expressing
      suboptimal levels of the individual isoforms of activase compared with wild-type
      plants or transgenic plants expressing levels of the beta-isoform sufficient for
      wild-type rates of photosynthesis. Net photosynthesis and Rubisco activation in
      transgenic plants expressing suboptimal amounts of the beta-isoform of activase
      from the Antarctic hairgrass were even more sensitive to inhibition by moderate
      heat stress than in the transgenic plants containing Arabidopsis activase. The
      results demonstrate that photosynthesis exhibits a similar sensitivity to
      inhibition by moderately high temperature in plants expressing either of the two
      different isoforms of activase. Thus, impairment of activase function under heat
      stress is not caused by oxidation of the redox-sensitive sulphydryls of the alpha
      isoform of activase. Instead, the results are consistent with thermal
      denaturation of activase under moderate heat stress, the effects of which on
      Rubisco activation would be enhanced when activase levels are suboptimal for
      photosynthesis.

PMID- 16997901
TI  - Whole plant responses, key processes, and adaptation to drought stress: the case
      of rice.
AB  - Most high-yielding rice cultivars developed for irrigated conditions, including
      the widely grown lowland variety IR64, are highly susceptible to drought stress.
      This limits their adoption in rainfed rice environments where there is a risk of
      water shortage during the growing season. Mapping studies using lowland-by-upland
      rice populations have provided limited information about the genetic basis of
      variation in yield under drought. One approach to simultaneously improve and
      understand rice drought tolerance is to generate backcross populations, select
      superior lines in managed stress environments, and then evaluate which features
      of the selected lines differ from the recurrent parent. This approach was been
      taken with IR64, using a range of tolerant and susceptible cultivars as donor
      parents. Yields of the selected lines measured across 13 widely contracting water
      environments were generally greater than IR64, but genotype-by-environment
      effects were large. Traits expected to vary between IR64 and selected lines are
      plant height, because many donors were not semi-dwarf types, and maturity,
      because selection in a terminal stress environment is expected to favour
      earliness. In these experiments it was found that some lines that performed
      better under upland drought were indeed taller than IR64, but that shorter lines
      with good yield under drought could also be identified. In trials where drought
      stress developed in previously flooded (lowland) fields, height was not
      associated with performance. There was little change in maturity with selection.
      Other notable differences between IR64 and the selected backcross lines were in
      their responses to applied ABA and ethylene in greenhouse experiments at the
      vegetative stage and in leaf rolling observed under chronic upland stress in the
      field. These observations are consistent with the hypothesis that adaptive
      responses to drought can effectively allow for improved performance across a
      broad range of water environments. The results indicate that the yield of IR64
      under drought can be significantly improved by backcrossing with selection under
      stress. In target environments where drought is infrequent but significant in
      certain years, improved IR64 with greater drought tolerance would be a valuable
      option for farmers.

PMID- 16997902
TI  - Effect of ascorbate oxidase over-expression on ascorbate recycling gene
      expression in response to agents imposing oxidative stress.
AB  - Ascorbate oxidase (AO) is a cell wall-localized enzyme that uses oxygen to
      catalyse the oxidation of ascorbate (AA) to the unstable radical
      monodehydroascorbate (MDHA) which rapidly disproportionates to yield
      dehydroascorbate (DHA) and AA, and thus contributes to the regulation of the AA
      redox state. Here, it is reported that in vivo lowering of the apoplast AA redox
      state, through increased AO expression in transgenic tobacco (Nicotiana tabacum
      L. cv. Xanthi), exerts no effects on the expression levels of genes involved in
      AA recycling under normal growth conditions, but plants display enhanced
      sensitivity to various oxidative stress-promoting agents. RNA blot analyses
      suggest that this response correlates with a general suppression of the plant's
      antioxidative metabolism as demonstrated by lower expression levels of AA
      recycling genes. Furthermore, studies using Botrytis cinerea reveal that
      transgenic plants exhibit increased sensitivity to fungal infection, although the
      response is not accompanied by a similar suppression of AA recycling gene
      expression. Our current findings, combined with previous studies which showed the
      contribution of AO in the regulation of AA redox state, suggest that the
      reduction in the AA redox state in the leaf apoplast of these transgenic plants
      results in shifts in their capacity to withstand oxidative stress imposed by
      agents imposing oxidative stress.

PMID- 16997903
TI  - Identification of genes controlled by the pregnane X receptor by microarray
      analysis of mRNAs from pregnenolone 16alpha-carbonitrile-treated rats.
AB  - Mammalian liver contains a pregnane X receptor (PXR, NR1I2), which binds drugs
      and other xenobiotics, and stimulates (or suppresses) expression of numerous
      genes involved in the metabolic elimination of foreign compounds and some toxic
      endogenous substances. In the present study, we used microarray analysis to
      identify genes whose expression in rat liver was significantly altered by
      pregnenolone 16alpha-carbonitrile (PCN) treatment. PCN is a synthetic steroid
      that induces cytochrome P4503A expression and is hepatoprotective by increasing
      resistance to subsequent stressful insults. Significant induction was seen for
      138 genes while expression of 82 genes was significantly repressed. We found
      induction of genes known to be induced by PCN, such as enzymes involved in drug
      metabolism and transport. In addition, many genes were differentially expressed
      whose functions concerned intracellular metabolism, transport of essential small
      molecules, cell cycle, and redox balance. Our results support the idea that the
      domain of PXR-controlled gene networks may be even more extensive than currently
      thought and may extend to functions apart from xenobiotic metabolism.

PMID- 16997904
TI  - Molecular basis for the GABAA receptor-mediated tonic inhibition in rat
      somatosensory cortex.
AB  - Fast inhibitory synaptic transmission is primarily mediated by synaptically
      released gamma-aminobutyric acid (GABA) acting on postsynaptic GABA(A) receptors.
      GABA acting on GABA(A) receptors produces not only phasic but also tonic
      inhibitions by persistent activation of extrasynaptic receptors. However, the
      mechanistic characteristics of tonic inhibition in the neocortex are not well
      understood. To address this, we studied pharmacologically isolated GABA(A)
      receptor-mediated currents in neocortical pyramidal neurons in rat brain slices.
      Bath application of bicuculline blocked miniature inhibitory postsynaptic
      currents (mIPSCs) and produced an outward shift in baseline holding current
      (I(hold)). Low concentrations of SR95531, a competitive GABA(A) receptor
      antagonist, abolished mIPSCs but had no significant effect on I(hold). The
      benzodiazepine midazolam produced an inward shift in I(hold) by augmenting tonic
      GABA(A) receptor-mediated currents, which were significantly greater in layer V
      neurons than in layer II/III. Single-cell reverse transcriptase-polymerase chain
      reaction (RT-PCR) revealed a relatively higher expressions of alpha1 and alpha5
      subunit mRNA in layer V neurons. L-655708, an alpha5 subunit-specific inverse
      agonist, reduced tonic currents in layer V but not in layer II/III neurons,
      whereas zolpidem, an alpha1-subunit agonist, exerted equivalent effects in both
      layers. These data suggest that the alpha1 GABA(A) receptor subunit is generally
      involved in tonic inhibition in pyramidal neurons of the neocortex, whereas the
      alpha5 subunit is specifically involved in layer V neurons.

PMID- 16997905
TI  - Differential parahippocampal and retrosplenial involvement in three types of
      visual scene recognition.
AB  - Human observers can quickly and accurately interpret the meaning of complex
      visual scenes. The neural mechanisms underlying this ability are largely
      unexplored. We used functional magnetic resonance imaging to measure cortical
      activity while subjects identified briefly presented scenes as specific familiar
      locations ("Houston Hall"), general place categories ("kitchen"), or general
      situational categories ("party"). Scene-responsive voxels in the parahippocampal
      place area (PPA) and retrosplenial cortex (RSC) were highly sensitive to
      recognition level when identifying scenes, responding more strongly during
      location identification than during place category or situation identification.
      In contrast, the superior temporal sulcus, cingulate sulcus, and supermarginal
      gyrus displayed the opposite pattern, responding more strongly during place
      category and situation identification. Consideration of results from 4
      experiments suggests that the PPA represents the visuospatial structure of
      individual scenes, whereas RSC supports processes that allow scenes to be
      localized within a larger extended environment. These results suggest that
      different scene identification tasks tap distinct cortical networks. In
      particular, we hypothesize that the PPA and RSC are critically involved in the
      identification of specific locations but play a less central role in other scene
      recognition tasks.

PMID- 16997906
TI  - Functional classification of amino acid decarboxylases from the alanine racemase
      structural family by phylogenetic studies.
AB  - Arginine decarboxylase (ADC) and ornithine decarboxylase (ODC) are involved in
      the biosynthesis of putrescine, which is the precursor of other polyamines in
      animals, plants, and bacteria. These pyridoxal-5'-phosphate-dependent
      decarboxylases belong to the alanine racemase (AR) structural family together
      with diaminopimelate decarboxylase (DapDC), which catalyzes the final step of
      lysine biosynthesis in bacteria. We have constructed a multiple-sequence
      alignment of decarboxylases in the AR structural family and, based on the
      alignment, inferred phylogenetic trees. The phylogenetic tree consists of 3
      distinct clades formed by ADC, DapDC, and ODC that diverged from an ancestral
      decarboxylase. The ancestral decarboxylase probably was able to recognize several
      substrates, and in archaea and bacteria, ODC may have retained the ability to
      bind other amino acids. Previously, a paralogue of ODC has been proposed to
      account for ADC activity detected in mammalian cells. According to our results,
      this appears unlikely, emphasizing the need for more caution in functional
      assignment made using sequence data and illustrating the continuing value of
      phylogenetic analysis in clarifying relationships and putative functions.

PMID- 16997907
TI  - Fossil calibration of molecular divergence infers a moderate mutation rate and
      recent radiations for pinus.
AB  - Silent mutation rate estimates for Pinus vary 50-fold, ranging from angiosperm
      like to among the slowest reported for plants. These differences either reflect
      extraordinary genomic processes or inconsistent fossil calibration, and they have
      important consequences for population and biogeographical inferences. Here we
      estimate mutation rates from 4 Pinus species that represent the major lineages
      using 11 nuclear and 4 chloroplast loci. Calibration was tested at the divergence
      of Pinus subgenera with the oldest leaf fossil from subg. Strobus (Eocene; 45
      MYA) or a recently published subg. Strobus wood fossil (Cretaceous; 85 MYA).
      These calibrations place the origin of Pinus 190-102 MYA and give absolute silent
      rate estimates of 0.70-1.31x10(-9) and 0.22-0.42x10(-9).site-1.year-1 for the
      nuclear and chloroplast genomes, respectively. These rates are approximately 4-
      to 20-fold slower than angiosperms, but unlike many previous estimates, they are
      more consistent with the high per-generation deleterious mutation rates observed
      in pines. Chronograms from nuclear and chloroplast genomes show that the
      divergence of subgenera accounts for about half of the time since Pinus diverged
      from Picea, with subsequent radiations occurring more recently. By extending the
      sampling to encompass the phylogenetic diversity of Pinus, we predict that most
      extant subsections diverged during the Miocene. Moreover, subsect. Australes,
      Ponderosae, and Contortae, containing over 50 extant species, radiated within a 5
      Myr time span starting as recently as 18 MYA. An Eocene divergence of pine
      subgenera (using leaf fossils) does not conflict with fossil-based estimates of
      the Pinus-Picea split, but a Cretaceous divergence using wood fossils
      accommodates Oligocene fossils that may represent modern subsections. Because
      homoplasy and polarity of character states have not been tested for fossil pine
      assignments, the choice of fossil and calibration node represents a significant
      source of uncertainty. Based on several lines of evidence (including agreement
      with ages inferred using calibrations outside of Pinus), we conclude that the 85
      MYA calibration at the divergence of pine subgenera provides a reasonable lower
      bound and that further refinements in age and mutation rate estimates will
      require a synthetic examination of pine fossil history.

PMID- 16997908
TI  - Rapid identification of P-glycoprotein substrates and inhibitors.
AB  - Identifying molecules that interact with P-glycoprotein (P-gp) is important for
      drug discovery but is also generally reliant on time-consuming in vitro and in
      vivo studies. As an alternative approach, the current study applied pharmacophore
      models and database screening to rapidly retrieve molecules that bind as
      substrates or inhibitors for P-gp from commercial databases and then confirmed
      their affinity as inhibitors in vitro. Seven molecules (acitretin,
      cholecalciferol, misoprostol, nafcillin, repaglinide, salmeterol, and
      telmisartan) with no published details for P-gp affinity, one positive control
      inhibitor (miconazole), and two negative control molecules (phenelzine and
      zonisamide) were selected for testing. The MDCK-MDR1 in vitro cell model was used
      to confirm their inhibitory effect on [3H]digoxin transport, and the ATPase assay
      was used as an additional in vitro tool to indicate P-gp activation. All seven
      test drugs were confirmed to have P-gp affinity. Additionally, our experimental
      results provided plausible explanations for the published pharmacokinetic
      profiles of the tested drugs and their classification according to the
      biopharmaceutics and drug disposition classification system. In this study, we
      showed the successful application of pharmacophore models to accurately predict P
      gp binding, which holds promise to anticipate drug-drug interactions from
      screening drug databases and a priori prediction of novel P-gp inhibitors or
      substrates.

PMID- 16997909
TI  - Drug-metabolizing enzyme inhibition by ketoconazole does not reduce
      interindividual variability of CYP3A activity as measured by oral midazolam.
AB  - Variable interindividual expression of cytochrome P450 3A presents a challenge in
      dosing drugs. The use of potent inhibitors of CYP3A such as ketoconazole has been
      explored to reduce the clearance of CYP3A substrates, thereby resulting in
      smaller dose requirements; however, the impact of CYP3A inhibition on
      interindividual variability has not been well characterized. Our objective was to
      examine the effect of ketoconazole inhibition on CYP3A metabolic variability as
      measured by the CYP3A biomarker oral midazolam. A single dose of midazolam (0.075
      mg/kg) was administered to 19 healthy Caucasian adults (38.7 +/- 8.8 years, nine
      male/10 female) at baseline and concurrently with ketoconazole (400 mg daily for
      10 days) on day 6 or 9 of ketoconazole. Plasma samples were collected over 6 to
      30 h. A paired t test and percent coefficient of variation (CV%) were used to
      evaluate differences in midazolam clearance and interindividual variability
      during both phases. Monte Carlo simulation was performed to determine probability
      distribution of area under the concentration-time curves (AUCs). Midazolam
      apparent oral clearance decreased by 89% (p < 0.0001) during inhibition. Cmax
      increased from 23 ng/ml (95% CI 19-29 ng/ml) to 55 ng/ml (95% CI 46-66 ng/ml), p
      < 0.0001. CV% increased from 41 to 58% from baseline to ketoconazole inhibition.
      AUCs [median (range)] were 0.20 mg . min/ml (0.05-0.81 mg . min/ml) and 1.94 mg .
      min/ml (0.25-25.4 mg . min/ml) at baseline and inhibition phase, with CV% of 41
      and 61%, respectively. Ketoconazole decreased CYP3A activity but did not reduce
      interindividual variability. Use of a CYP3A inhibitor to standardize dosing of
      CYP3A substrates may not be feasible in clinical practice.

PMID- 16997910
TI  - Peracetylation as a means of enhancing in vitro bioactivity and bioavailability
      of epigallocatechin-3-gallate.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) is the widely studied catechin in green tea
      (Camellia sinensis). Previously, we have reported the low bioavailability of EGCG
      in rats and mice. As a means of improving the bioavailability of EGCG, we have
      prepared a peracetylated EGCG derivative (AcEGCG) and herein report its growth
      inhibitory activity and cellular uptake in vitro, as well as bioavailability in
      mice. AcEGCG exhibited enhanced growth inhibitory activity relative to EGCG in
      both KYSE150 human esophageal (IC50 = 10 versus 20 microM) and HCT116 human colon
      cancer cells (IC50 = 32 versus 45 microM). AcEGCG was rapidly converted to EGCG
      by HCT116 cells, and treatment of cells with AcEGCG resulted in a 2.8- to 30-fold
      greater intracellular concentration of EGCG as compared with treatment with EGCG.
      AcEGCG was also more potent than EGCG at inhibiting nitric oxide production (4.4
      fold) and arachidonic acid release (2.0-fold) from lipopolysaccharide-stimulated
      RAW264.7 murine macrophages. Intragastric administration of AcEGCG to CF-1 mice
      resulted in higher bioavailability compared with administration of equimolar
      doses of EGCG. The plasma area under the curve from 0 to infinity (AUC0-
      >infinity) of total EGCG was 465.0 and 194.6 [(microg/ml) . min] from the
      administration of AcEGCG and EGCG, respectively. The t1/2 of EGCG was also
      increased following administration of AcEGCG compared with EGCG (441.0 versus
      200.3 min). The AUC0-->infinity and t1/2 were also increased in small intestinal
      (2.8- and 4.3-fold, respectively) and colonic tissues (2.4- and 6.0-fold,
      respectively). These data suggest that acetylation represents a means of
      increasing the biological potency in vitro, increasing the bioavailability of
      EGCG in vivo, and may improve cancer-preventive activity.

PMID- 16997911
TI  - Structure-activity relationship and elucidation of the determinant factor(s)
      responsible for the mechanism-based inactivation of cytochrome P450 2B6 by
      substituted phenyl diaziridines.
AB  - It has been demonstrated previously that several 3-trifluoromethyl-3-(4
      alkoxyphenyl)diaziridines inhibit the 7-ethoxy-4-(trifluoroethyl)coumarin (7-EFC)
      O-deethylation activity of P450 2B6 in a mechanism-based manner. In contrast, 3
      trifluoromethyl-3-(4-methylthio)phenyl)diaziridine did not have any effect on the
      activity of P450 2B6. It is interesting that both the alkoxy and the thiophenyl
      compounds were metabolized by P450 2B6. In this report, the structure-activity
      relationships for the mechanism-based inactivation of cytochrome P450 2B6 by a
      series of aryl diaziridines were investigated. Three diaziridines that did not
      contain a 4-alkoxy-substituent on their phenyl ring, namely, 3-trifluoromethyl-3
      (3-methoxyphenyl)diaziridine, 3-trifluoromethyl-3-phenyl diaziridine, and 3
      trifluoromethyl-3-(4-chlorophenyl)diaziridine had no effect on the P450 2B6 7-EFC
      activity. Another analog that did not contain a diaziridine substructure, 3
      trifluoromethyl-3-(4-methoxyphenyl)ethanone, also had no effect on the activity
      of P450 2B6. Glutathione ethyl ester adducts of the phenyldiaziridine reactive
      intermediates were isolated from reaction mixtures of the inactivated samples and
      analyzed by liquid chromatography-tandem mass spectrometry. The structures of the
      conjugates suggested that the electrophilic reactive intermediate in each case
      was a quinone methide (quinomethane), 4-ethylidene-cyclohexa-2,5-dienone,
      generated from the 4-alkoxyphenyldiaziridines by removal of both of the
      diaziridine and the 4-alkyl groups. In conclusion, the determinant factor for the
      mechanism-based inactivator activity of the aryl diaziridines seems to be the
      formation of the reactive quinomethane intermediate, which is generated from the
      4-alkoxyphenyl diaziridines by a cytochrome P450-catalyzed metabolic reaction.

PMID- 16997912
TI  - CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O
      demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan
      bis-O-methylamidoxime].
AB  - DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime] is biotransformed to
      the potent antiparasitic diamidine DB75 [2,5-bis(4-amidinophenyl) furan] by
      sequential oxidative O-demethylation and reductive N-dehydroxylation reactions.
      Previous work demonstrated that the N-dehydroxylation reactions are catalyzed by
      cytochrome b5/NADH-cytochrome b5 reductase. Enzymes responsible for catalyzing
      the DB289 O-demethylation pathway have not been identified. We report an in vitro
      metabolism study to characterize enzymes in human liver microsomes (HLMs) that
      catalyze the initial O-demethylation of DB289 (M1 formation). Potent inhibition
      by 1-aminobenzotriazole confirmed that M1 formation is catalyzed by P450 enzymes.
      M1 formation by HLMs was NADPH-dependent, with a Km and Vmax of 0.5 microM and
      3.8 nmol/min/mg protein, respectively. Initial screening showed that recombinant
      CYP1A1, CYP1A2, and CYP1B1 were efficient catalysts of M1 formation. However,
      none of these three enzymes was responsible for M1 formation by HLMs. Further
      screening showed that recombinant CYP2J2, CYP4F2, and CYP4F3B could also catalyze
      M1 formation. An antibody against CYP4F2, which inhibited both CYP4F2 and
      CYP4F3B, inhibited 91% of M1 formation by HLMs. Two inhibitors of P450-mediated
      arachidonic acid metabolism, HET0016 (N-hydroxy-N'-(4-n-butyl-2
      methylphenyl)formamidine) and 17-octadecynoic acid, effectively inhibited M1
      formation by HLMs. Inhibition studies with ebastine and antibodies against CYP2J2
      suggested that CYP2J2 was not involved in M1 formation by HLMs. Additionally,
      ketoconazole preferentially inhibited CYP4F2, but not CYP4F3B, and partially
      inhibited M1 formation by HLMs. We conclude that CYP4F enzymes (e.g., CYP4F2,
      CYP4F3B) are the major enzymes responsible for M1 formation by HLMs. These
      findings indicate that, in human liver, members of the CYP4F subfamily
      biotransform not only endogenous compounds but also xenobiotics.

PMID- 16997914
TI  - Helix 8 of the viral chemokine receptor ORF74 directs chemokine binding.
AB  - The constitutively active G-protein-coupled receptor and viral oncogene ORF74,
      encoded by Kaposi sarcoma-associated herpesvirus (human herpesvirus 8), binds a
      broad range of chemokines, including CXCL1 (agonist), CXCL8 (neutral ligand), and
      CXCL10 (inverse agonist). Although chemokines interact with the extracellular N
      terminus and loops of the receptor, we demonstrate that helix 8 (Hx8) in the
      intracellular carboxyl tail (C-tail) of ORF74 directs chemokine binding. Partial
      deletion of the C-tail resulted in a phenotype with reduced constitutive activity
      but intact regulation by ligands. Complete deletion of the C-tail, including Hx8,
      resulted in an inactive phenotype that lacks CXCL8 binding sites and has an
      increased number of binding sites for CXCL10. Similar effects were obtained with
      the single R7.61(322)W or Q7.62(323)P mutations in Hx8. We propose that the
      conserved charged or polar side chain at position 7.61 has a specific role in
      stabilizing the end of transmembrane domain 7 (TM7). Disruption of Hx8 by
      deletion or mutation distorts an H-bonding network, involving highly conserved
      amino acids within TM2, TM7, and Hx8, that is crucial for positioning of the TM
      domains, coupling to Galphaq, and CXCL8 binding. Thus, Hx8 appears to exert a key
      role in receptor stabilization through the conserved residue R7.61, directing the
      ligand binding profile of ORF74 and likely also that of other class A G-protein
      coupled receptors.

PMID- 16997913
TI  - Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and
      resistance due to their loss is overcome by a BH3 mimetic.
AB  - Cell killing is a critical pharmacological activity of imatinib to eradicate
      Bcr/Abl+ leukemias. We found that imatinib kills Bcr/Abl+ leukemic cells by
      triggering the Bcl-2-regulated apoptotic pathway. Imatinib activated several
      proapoptotic BH3-only proteins: bim and bmf transcription was increased, and both
      Bim and Bad were activated posttranslationally. Studies using RNAi and cells from
      gene-targeted mice revealed that Bim plays a major role in imatinib-induced
      apoptosis of Bcr/Abl+ leukemic cells and that the combined loss of Bim and Bad
      abrogates this killing. Loss of Bmf or Puma had no effect. Resistance to imatinib
      caused by Bcl-2 overexpression or loss of Bim (plus Bad) could be overcome by
      cotreatment with the BH3 mimetic ABT-737. These results demonstrate that Bim and
      Bad account for most, perhaps all, imatinib-induced killing of Bcr/Abl+ leukemic
      cells and suggest previously undescribed drug combination strategies for cancer
      therapy.

PMID- 16997915
TI  - HCF164 receives reducing equivalents from stromal thioredoxin across the
      thylakoid membrane and mediates reduction of target proteins in the thylakoid
      lumen.
AB  - HCF164 is a membrane-anchored thioredoxin-like protein known to be indispensable
      for assembly of cytochrome b6 f in the thylakoid membranes. In this study, we
      report the finding that chloroplast stroma m-type thioredoxin is the source of
      reducing equivalents for reduction of HCF164 in the thylakoid lumen, providing
      strong evidence that higher plant chloroplasts possess a trans-membrane reducing
      equivalent transfer system similar to that found in bacteria. To probe the
      function of HCF164 in the lumen, a screen to identify the reducing equivalent
      acceptor proteins of HCF164 was carried out by using a resin-immobilized HCF164
      single cysteine mutant, leading to the isolation of putative target thylakoid
      proteins. Among the newly identified target proteins, the reduction of the PSI-N
      subunit of photosystem I by HCF164 was confirmed both in vitro and in isolated
      thylakoids. Two components of the cytochrome b6 f complex, the cytochrome f and
      Rieske FeS proteins, were also identified as novel potential target proteins. The
      data presented here suggest that HCF164 serves as an important transducer of
      reducing equivalents to proteins in the thylakoid lumen.

PMID- 16997916
TI  - KRAB can repress lentivirus proviral transcription independently of integration
      site.
AB  - The KRAB transcriptional repressor domain, commonly found in zinc finger
      proteins, acts by inducing the formation of heterochromatin. We previously
      exploited this property to achieve drug-regulated transgenesis and knock down by
      combining doxycycline-controllable KRAB-containing fusion proteins and lentiviral
      vectors. Here, we asked whether KRAB-induced repression is widespread or limited
      to specific regions of the genome. For this, we transduced cells with a
      lentiviral vector expressing a target reporter and a KRAB-containing
      transcriptional repressor from a bicistronic mRNA. We found that approximately
      1.4% of the resulting proviruses escaped repression. However, this phenotype
      could be reverted by expressing the KRAB-containing protein in trans.
      Accordingly, the irrepressible proviruses all contained, in the DNA sequence
      encoding the KRAB-containing effector or its upstream internal ribosomal entry
      site, mutations or deletions likely resulting from errors or recombination during
      reverse transcription. These results indicate that KRAB-induced transcriptional
      repression is robust and active over a variety of genomic contexts that include
      at least the wide range of sites targeted by lentiviral integration.

PMID- 16997917
TI  - Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and
      Pou5f1 promoters.
AB  - Nobox (newborn ovary homeobox gene) deficiency disrupts early folliculogenesis
      and the expression of oocyte-specific genes in mice. Here, we identified several
      cis-acting sites, TAATTG, TAGTTG, and TAATTA as NOBOX DNA binding elements (NBEs)
      using a library of randomly generated oligonucleotides by cyclic amplification of
      sequence target assay and mutation analyses. We show that NOBOX preferentially
      binds to the NOBOX binding elements with high affinity. In addition, we found
      that promoter regions of mouse Pou5f1 and Gdf9 contain one (-426) and three NOBOX
      binding elements (-786, -967, and -1259), respectively. NOBOX binds to these
      putative NOBOX binding elements with high affinity and augmented transcriptional
      activity of luciferase reporter driven by mouse Pou5f1 and Gdf9 promoters
      containing the NOBOX binding elements. In chromatin immunoprecipitation assays,
      DNA sequences from Pou5f1 and Gdf9 promoters co-precipitated with anti-NOBOX
      antibody. These results suggest that NOBOX directly regulates the transcription
      of Pou5f1 and Gdf9 in oocytes during early folliculogenesis.

PMID- 16997918
TI  - The chemistry of phospholipid binding by the Saccharomyces cerevisiae
      phosphatidylinositol transfer protein Sec14p as determined by EPR spectroscopy.
AB  - The major yeast phosphatidylinositol/phosphatidylcholine transfer protein Sec14p
      is the founding member of a large eukaryotic protein superfamily. Functional
      analyses indicate Sec14p integrates phospholipid metabolism with the membrane
      trafficking activity of yeast Golgi membranes. In this regard, the ability of
      Sec14p to rapidly exchange bound phospholipid with phospholipid monomers that
      reside in stable membrane bilayers is considered to be important for Sec14p
      function in cells. How Sec14p-like proteins bind phospholipids remains unclear.
      Herein, we describe the application of EPR spectroscopy to probe the local
      dynamics and the electrostatic microenvironment of phosphatidylcholine (PtdCho)
      bound by Sec14p in a soluble protein-PtdCho complex. We demonstrate that PtdCho
      movement within the Sec14p binding pocket is both anisotropic and highly
      restricted and that the C5 region of the sn-2 acyl chain of bound PtdCho is
      highly shielded from solvent, whereas the distal region of that same acyl chain
      is more accessible. Finally, high field EPR reports on a heterogeneous polarity
      profile experienced by a phospholipid bound to Sec14p. Taken together, the data
      suggest a headgroup-out orientation of Sec14p-bound PtdCho. The data further
      suggest that the Sec14p phospholipid binding pocket provides a polarity gradient
      that we propose is a primary thermodynamic factor that powers the ability of
      Sec14p to abstract a phospholipid from a membrane bilayer.

PMID- 16997919
TI  - Histopathological risk factors for lymph node metastasis in submucosal invasive
      colorectal carcinoma of pedunculated or semipedunculated type.
AB  - AIMS: To evaluate the histopathological risk factors for lymph node metastasis in
      cases of pedunculated or semipedunculated submucosal invasive colorectal
      carcinoma (SICC). METHODS: A total of 48 patients with non-sessile SICC who
      underwent systematic lymph node dissection were included. Tumour size,
      histological grade, angiolymphatic invasion, tumour budding, dedifferentiation,
      objective submucosal invasion depth from the identified muscularis mucosa,
      relative invasion depth of the submucosal layer, and depth of stalk invasion were
      investigated histopathologically. RESULTS: Lymph node metastasis was observed in
      seven cases (14.6%). Univariate analysis showed angiolymphatic invasion and
      tumour budding to be significantly associated with lymph node metastasis.
      Multivariate analysis showed that tumour budding was the only independent factor
      associated with lymph node metastasis in cases of non-sessile SICC. CONCLUSIONS:
      Results indicate that tumour budding is a useful risk factor for predicting lymph
      node metastasis in cases of pedunculated or semipedunculated SICC.

PMID- 16997921
TI  - Bayesian statistics.

PMID- 16997920
TI  - K-ras mutations and cell kinetics in Helicobacter pylori associated gastric
      intestinal metaplasia: a comparison before and after eradication in patients with
      chronic gastritis and gastric cancer.
AB  - BACKGROUND: Helicobacter pylori related gastric intestinal metaplasia (IM) is
      considered to be a precancerous lesion. AIMS: To identify the effects of H pylori
      eradication on K-ras mutations, cell kinetics in IM and histological changes in
      patients with and without gastric cancers in a one-year prospective study.
      METHODS: Patients included group A (n = 39), chronic gastritis, and group B (n =
      53), intestinal-type early gastric cancer patients who had all undergone
      endoscopic mucosal resection (n = 25) or surgical resection (n = 28). K-ras codon
      12 mutations in IM were examined, followed by DNA sequencing analysis.
      Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and
      using the TUNEL method, respectively. RESULTS: The incidence of K-ras mutations
      in the cancer was only 3.8%. The mutant K-ras in IM was observed more frequently
      in group A (46.2%) than in group B patients (1.9%) (p<0.005). After eradication,
      the K-ras mutations significantly declined to 12.8% in group A (p<0.005). The
      mutation pattern of K-ras codon 12 before eradication was that GGT was mainly
      changed to AGT (50%) in group A. AGT transformation was not affected by
      treatment. Apoptosis in IM showed an increase after H pylori eradication in both
      groups (p<0.05 in group A) although no histological improvement in IM was
      observed. The monocyte score was significantly higher in group A than in group B
      (p<0.05); the score improved significantly after eradication. CONCLUSIONS: K-ras
      mutations in IM do not always play a role in gastric carcinogenesis but cell
      kinetics, especially apoptosis, in IM may contribute to it. There are early
      events in K-ras mutations which are influenced by H pylori infection; some
      mutations may also be selected by eradication. These unstable K-ras mutations in
      IM may be related to lymphocyte infiltration caused by H pylori infection.

PMID- 16997922
TI  - Posterior progress.

PMID- 16997923
TI  - Impact of model, methodological, and parameter uncertainty in the economic
      analysis of vaccination programs.
AB  - Guidelines for economic evaluations insist that the sensitivity of model results
      to alternative parameter values should be thoroughly explored. However,
      differences in model construction and analytical choices (such as the choice of a
      cost-effectiveness or cost-benefit framework) also introduce uncertainty in
      results, though these are rarely subjected to a thorough sensitivity analysis. In
      this article, the authors quantify the effect of model, methodological, and
      parameter uncertainty, taking varicella vaccination as an example. They used 3
      different models (a static model, a dynamic model that only looks at the effect
      of vaccination on varicella, and a dynamic model that also assesses the
      implications of vaccination for zoster epidemiology) and 2 forms of analysis
      (cost-benefit and cost-utility). They also varied the discount rate and time
      frame of analysis. Probabilistic sensitivity analyses were performed to estimate
      the impact of parameter uncertainty. In their example, model and methodological
      choice had a profound effect on estimated cost-effectiveness, but parameter
      uncertainty played a relatively minor role. Under cost-utility analysis, the
      probabilistic sensitivity analysis suggested that there was a near certainty that
      vaccination dominates no vaccination, or the other way around, depending on model
      choice and perspective. Under cost-benefit analysis, vaccination always appeared
      to be attractive. Thus, the authors clearly show that model and methodological
      assumptions can have greater impact on results than parameter estimates, although
      sensitivity analyses are rarely performed on these sources of uncertainty.

PMID- 16997924
TI  - The impact of unmeasured clinical variables on the accuracy of hospital report
      cards: a Monte Carlo study.
AB  - PURPOSE: Hospital report cards are commonly produced using administrative data.
      The objective of this study was to determine the impact of unmeasured clinical
      data on the accuracy of hospitals' report cards. METHODS: Monte Carlo simulations
      were based on both administrative and detailed clinical data for patients
      hospitalized with an acute myocardial infarction in Ontario, Canada. Data were
      simulated such that the true performance of each hospital was known. Both
      clinical and administrative risk scores were randomly generated for each patient.
      The ability of hospital report cards to correctly identify hospitals that truly
      had higher than acceptable mortality was compared when both clinical and
      administrative data were used and when only administrative data were used. By
      using Monte Carlo simulations, we were able to incrementally increase the
      divergence between the 2 risk scores. RESULTS: In a wide range of settings,
      sensitivity and specificity of hospital report cards was only negligibly greater
      when both administrative and clinical data were used compared to when only
      administrative data were used. CONCLUSIONS: Unmeasured clinical data have at most
      a minor impact on the accuracy of cardiac hospital report cards.

PMID- 16997925
TI  - Collective equipoise, disappointment, and the therapeutic misconception: on the
      consequences of selection for clinical research.
AB  - Private information induces individuals to self-select as subjects into clinical
      research trials, and it induces researchers to select which trials they conduct.
      The authors show that selection can induce ex ante therapeutic misconception and
      ex post disappointment among research subjects, and it undermines the rationale
      of collective equipoise as an ethical basis for clinical trials. Selection
      provides a reason to make nontrivial payments to subjects, and it implies that
      researchers should not design experiments to maximize statistical power.

PMID- 16997926
TI  - An iterative Bayesian approach to health technology assessment: application to a
      policy of preoperative optimization for patients undergoing major elective
      surgery.
AB  - PURPOSE: This article presents an iterative framework for managing the dynamic
      process of health technology assessment. The framework uses Bayesian statistical
      decision theory and value of information (VOI) analysis to inform decision making
      regarding appropriate patient management and to direct future research effort
      over the lifetime of a technology. Within the article, the framework is applied
      to a policy decision regarding preoperative patient management before major
      elective surgery, for which trial data are available. METHOD: The evidence
      available prior to the trial is used to determine the appropriate method of
      patient management and to ascertain whether, at the time of commissioning, the
      trial was potentially worthwhile. The prior information is then updated with the
      trial data via a Bayesian analysis using informative priors. This post trial
      information set is then used to reassess the appropriate method for patient
      management and to determine whether there is a requirement for any further
      research. RESULTS: Prior to the trial, preoperative optimization with dopexamine
      is identified as the appropriate method of patient management. The results of the
      VOI analysis suggest that a short-term trial was potentially worthwhile
      (population expected value of perfect information [EVPI] = 48 million pounds
      sterling). Following the trial, the uncertainty surrounding the choice of
      appropriate patient management and the potential worth of further research had
      increased (population EVPI = 67 million pounds sterling). CONCLUSIONS: The
      article demonstrates the value and practicality of applying the iterative
      framework to the dynamic process of health technology assessment. It is only by
      formally incorporating all of the information available to decision makers,
      through informed priors, that the appropriate decisions can be made.

PMID- 16997927
TI  - Estimation of mortality rates for disease simulation models using Bayesian
      evidence synthesis.
AB  - PURPOSE: The authors propose a Bayesian approach for estimating competing risks
      for inputs to disease simulation models. This approach is suggested when modeling
      a disease that causes a large proportion of all-cause mortality, particularly
      when mortality from the disease of interest and other-cause mortality are both
      affected by the same risk factor. METHODS: The authors demonstrate a Bayesian
      evidence synthesis by estimating other-cause mortality, stratified by smoking
      status, for use in a simulation model of lung cancer. National (US) survey data
      linked to death registries (National Health Interview Survey [NHIS]--Multiple
      Cause of Death files) were used to fit cause-specific hazard models for 3 causes
      of death (lung cancer, heart disease, and all other causes), controlling for age,
      sex, race, and smoking status. Synthesis of NHIS data with national vital
      statistics data on numbers and causes of deaths was performed in WinBUGS (version
      1.4.1, MRC Biostatistics Unit, UK). Correction for inconsistencies between the
      NHIS and vital statistics data is described. A published cohort study was a
      source of prior information for smoking-related mortality. RESULTS: Marginal
      posterior densities of annual mortality rates for lung cancer and other-cause
      death (further divided into heart disease and all other causes), stratified by 5
      year age interval, race (white and black), gender, and smoking status (current,
      former, never), were estimated, specific to a time period (1987-1995). Overall,
      black current smokers experienced the highest mortality rates. CONCLUSIONS:
      Bayesian evidence synthesis is an effective method for estimation of cause
      specific mortality rates, stratified by demographic factors.

PMID- 16997928
TI  - Large-sample Bayesian posterior distributions for probabilistic sensitivity
      analysis.
AB  - In probabilistic sensitivity analyses, analysts assign probability distributions
      to uncertain model parameters and use Monte Carlo simulation to estimate the
      sensitivity of model results to parameter uncertainty. The authors present
      Bayesian methods for constructing large-sample approximate posterior
      distributions for probabilities, rates, and relative effect parameters, for both
      controlled and uncontrolled studies, and discuss how to use these posterior
      distributions in a probabilistic sensitivity analysis. These results draw on and
      extend procedures from the literature on large-sample Bayesian posterior
      distributions and Bayesian random effects meta-analysis. They improve on standard
      approaches to probabilistic sensitivity analysis by allowing a proper accounting
      for heterogeneity across studies as well as dependence between control and
      treatment parameters, while still being simple enough to be carried out on a
      spreadsheet. The authors apply these methods to conduct a probabilistic
      sensitivity analysis for a recently published analysis of zidovudine prophylaxis
      following rapid HIV testing in labor to prevent vertical HIV transmission in
      pregnant women.

PMID- 16997929
TI  - A simulation model to estimate the cost and effectiveness of alternative dialysis
      initiation strategies.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) require dialysis to
      maintain survival. The optimal timing of dialysis initiation in terms of cost
      effectiveness has not been established. METHODS: We developed a simulation model
      of individuals progressing towards ESRD and requiring dialysis. It can be used to
      analyze dialysis strategies and scenarios. It was embedded in an optimization
      frame worked to derive improved strategies. RESULTS: Actual (historical) and
      simulated survival curves and hospitalization rates were virtually
      indistinguishable. The model overestimated transplantation costs (10%) but it was
      related to confounding by Medicare coverage. To assess the model's robustness, we
      examined several dialysis strategies while input parameters were perturbed. Under
      all 38 scenarios, relative rankings remained unchanged. An improved policy for a
      hypothetical patient was derived using an optimization algorithm. CONCLUSION: The
      model produces reliable results and is robust. It enables the cost-effectiveness
      analysis of dialysis strategies.

PMID- 16997930
TI  - Increasing the efficiency of Monte Carlo cohort simulations with variance
      reduction techniques.
AB  - The authors discuss techniques for Monte Carlo (MC) cohort simulations that
      reduce the number of simulation replications required to achieve a given degree
      of precision for various output measures. Known as variance reduction techniques,
      they are often used in industrial engineering and operations research models, but
      they are seldom used in medical models. However, most MC cohort simulations are
      well suited to the implementation of these techniques. The authors discuss the
      cost of implementation versus the benefit of reduced replications.

PMID- 16997932
TI  - The effect of fibroids without cavity involvement on ART outcomes independent of
      ovarian age.
AB  - BACKGROUND: The effect of fibroids that do not distort the endometrial cavity on
      pregnancy rate (PR) and implantation rate (IR) is controversial. Use of oocyte
      donor-derived embryos offers an ideal patient population to study the effect of
      fibroids in patients utilizing assisted reproductive technologies (ARTs).
      METHODS: We conducted a retrospective cohort study of patients undergoing oocyte
      donor recipient (ODR) IVF cycles at two tertiary care fertility centres. We
      examined medical records for the presence of non-cavity-distorting fibroids and
      evaluated subsequent PR and IR. RESULTS: Three hundred and sixty-nine patients,
      94 with fibroids, underwent oocyte donor recipient transfer cycles with fresh
      embryos. There was no statistical difference in IR (36 versus 38%) or clinical PR
      (47 versus 54%) between patients with or without fibroids. Neither the location
      (subserosal versus intramural) and the presence of multiple myomas nor the size
      of the myomas affected outcomes. Fibroids were more likely to be present in
      patients with increasing recipient age. CONCLUSIONS: Clinical PR and IR are not
      affected by the presence of non-cavity-distorting leiomyomata. This evidence does
      not support myomectomy before ART in patients with asymptomatic fibroids that do
      not significantly distort the endometrial cavity or cause abnormal uterine
      bleeding.

PMID- 16997931
TI  - Mucin gene expression in human male urogenital tract epithelia.
AB  - BACKGROUND: Mucins are large, hydrophilic glycoproteins that protect wet-surfaced
      epithelia from pathogen invasion as well as provide lubrication. At least 17
      mucin genes have been cloned to date. This study sought to determine the mucin
      gene expression profile of the human male urogenital tract epithelia, to
      determine if mucins are present in seminal fluid and to assess the effect of
      androgens on mucin expression. METHODS AND RESULTS: Testis, epididymis, vas
      deferens, seminal vesicle, prostate, bladder, urethra and foreskin were assessed
      for mucin expression by RT-PCR (for 14 mucin genes) and immunohistochemistry
      (nine antibodies for five mucins). Epithelia of the vas deferens, prostate and
      urethra expressed the greatest number of mucins, each with mRNA for between 5 and
      8 mucins. Except for MUC20 in epididymis, mRNA for MUC1 and MUC20, both membrane
      associated mucins, was detected in all tissues analysed. By comparison, MUC6 was
      more restricted in expression, being primarily detected in seminal vesicle. MUC1,
      MUC5B and MUC6 were detected in seminal fluid samples by immunoblot analysis.
      Androgens had no effect on mucin expression in cultured human prostatic
      epithelial cells. CONCLUSIONS: Each region of urogenital tract epithelium
      expressed a unique mucin gene repertoire. Secretory mucins are present in seminal
      fluid, and androgens do not appear to regulate mucin gene expression in prostatic
      epithelial cells in culture.

PMID- 16997933
TI  - Ovarian leukocyte distribution and cytokine/chemokine mRNA expression in
      follicular fluid cells in women with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) affects 5-10% of reproductive-aged
      women and is commonly associated with anovulatory infertility. Leukocytes,
      together with granulosa cells, may contribute to the pathogenesis of PCOS via
      their ability to secrete an array of cytokines implicated in follicle growth. The
      aim of this study was to examine leukocyte subtypes in follicular phase ovaries
      and to quantify cytokine and chemokine mRNA expression in follicular fluid cells
      obtained at the time of oocyte retrieval before IVF in women with and without
      PCOS. METHODS: Ovaries were immunostained for various leukocyte markers [CD3,
      CD4, CD14, CD15, CD45, CD45RA, CD45RO, CD57 and major histocompatibility complex
      (MHC) class II]. In addition, follicular fluid cells were subjected to
      quantitative RT-PCR to evaluate colony-stimulating factor-1 (CSF-1), granulocyte
      macrophage (GM)-CSF, interleukins (IL-1beta, IL-6, IL-8 and IL-10), monocyte
      chemotactic protein (MCP-1) and tumour necrosis factor (TNFalpha) mRNA expression
      relative to beta-actin. RESULTS: CD45RO+ cells (activated/memory T lymphocytes)
      were reduced by 60% in the theca layer of follicles from PCOS women. The relative
      abundance of macrophages and neutrophils was unchanged. Cytokine and chemokine
      mRNA transcripts examined were not affected by PCOS status. There was an
      association between high BMI and high TNFalpha and low IL-6 mRNA expression in
      follicular cells. IL-6 expression was higher in women who subsequently achieved
      pregnancy. CONCLUSIONS: T lymphocytes potentially play a role in the local
      pathological mechanisms of PCOS. Further studies are required to identify their
      contribution to the aetiology of this common condition.

PMID- 16997934
TI  - Morphology assessment and fluorescence in situ hybridization of the same
      spermatozoon using a computerized cell-scanning system.
AB  - BACKGROUND: Poor sperm morphology is statistically associated with an increase in
      the incidence of chromosome abnormalities. Our aim was to examine the possible
      correlation between chromosomal aberrations and sperm morphology in the same
      cell. METHODS: 12349 spermatozoa from 7 teratozoospermic and one globozoospermic
      patients, and from 3 fertile donors were analyzed using a system which scans for
      cell morphology and chromosomal ploidy in the same cell using digital technology.
      RESULTS: Chromosomal aberrations were detected in 5.3% of teratozoospermic cases
      and in 6.7% in the globozoospermic patient compared with 1.6% in donors (P <
      0.0001). Chromosomal aberrations were more common in abnormally formed sperm
      compared with normal spermatozoa: 4.5% vs 1.3% in the teratozoospermic group and
      2.0% vs 0.3% in the control group (NS), especially frequent among sperm with two
      heads or two tails (52.1-77.2%) or extreme head deformations (10.6-11.1%)
      irrespective of grouping, and in mild amorphous heads in the globozoospermic
      patients (20.2%). The frequency of chromosomal aberrations in morphologically
      normal sperm was comparable whether derived from teratozoospermic or normospermic
      patients. CONCLUSIONS: The computerized cell-scanning system demonstrated the
      relationship between chromosomal aberrations and sperm morphology in the same
      spermatozoon. The incidence of chromosomal aberrations was positively linked to
      abnormal sperm morphology, the more severe the abnormality, the higher the
      incidence of aneuploidy.

PMID- 16997935
TI  - Pregnancy is predictable: a large-scale prospective external validation of the
      prediction of spontaneous pregnancy in subfertile couples.
AB  - BACKGROUND: Prediction models for spontaneous pregnancy may be useful tools to
      select subfertile couples that have good fertility prospects and should therefore
      be counselled for expectant management. We assessed the accuracy of a recently
      published prediction model for spontaneous pregnancy in a large prospective
      validation study. METHODS: In 38 centres, we studied a consecutive cohort of
      subfertile couples, referred for an infertility work-up. Patients had a regular
      menstrual cycle, patent tubes and a total motile sperm count (TMC) >3 x 10(6).
      After the infertility work-up had been completed, we used a prediction model to
      calculate the chance of a spontaneous ongoing pregnancy
      (www.freya.nl/probability.php). The primary end-point was time until the
      occurrence of a spontaneous ongoing pregnancy within 1 year. The performance of
      the pregnancy prediction model was assessed with calibration, which is the
      comparison of predicted and observed ongoing pregnancy rates for groups of
      patients and discrimination. RESULTS: We included 3021 couples of whom 543 (18%)
      had a spontaneous ongoing pregnancy, 57 (2%) a non-successful pregnancy, 1316
      (44%) started treatment, 825 (27%) neither started treatment nor became pregnant
      and 280 (9%) were lost to follow-up. Calibration of the prediction model was
      almost perfect. In the 977 couples (32%) with a calculated probability between 30
      and 40%, the observed cumulative pregnancy rate at 12 months was 30%, and in 611
      couples (20%) with a probability of >or=40%, this was 46%. The discriminative
      capacity was similar to the one in which the model was developed (c-statistic
      0.59). CONCLUSIONS: As the chance of a spontaneous ongoing pregnancy among
      subfertile couples can be accurately calculated, this prediction model can be
      used as an essential tool for clinical decision-making and in counselling
      patients. The use of the prediction model may help to prevent unnecessary
      treatment.

PMID- 16997936
TI  - Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and
      cell number in IVF.
AB  - BACKGROUND: The aim of this study was to investigate the effect of treatment with
      dehydroepiandrosterone (DHEA) on fertility outcomes among women with diminished
      ovarian reserve. MATERIALS AND METHODS: This is a case-control study in an
      academically affiliated private infertility centre. Twenty-five women with
      significantly diminished ovarian reserve had one IVF cycle before and after DHEA
      treatment, with otherwise identical hormonal stimulation. Women received 75 mg of
      DHEA daily (25 mg three times daily) for an average of 17.6 +/- 2.13 weeks. We
      performed a comparison of IVF outcome parameters, before and after DHEA
      treatment, including peak estradiol (E(2)) levels, oocyte and embryo numbers,
      oocyte and embryo quality and embryo transfer statistics. RESULTS: Paired
      analysis of IVF cycle outcomes in 25 patients, who underwent cycles both before
      and after DHEA supplementation, demonstrated significant increases in fertilized
      oocytes (P < 0.001), normal day 3 embryos (P = 0.001), embryos transferred (P =
      0.005) and average embryo scores per oocyte (P < 0.001) after DHEA treatment.
      CONCLUSION: This study confirms the previously reported beneficial effects of
      DHEA supplementation on ovarian function in women with diminished ovarian
      reserve.

PMID- 16997937
TI  - The effect of rosiglitazone in the prevention of intra-abdominal adhesion
      formation in a rat uterine horn model.
AB  - BACKGROUND: Effects of rosiglitazone in the prevention of adhesion formation were
      evaluated. METHODS: Eighty Wistar albino rats were randomly grouped into eight
      equally sized groups. A 2-cm segment of the antimesenteric surface of the right
      uterine horn was traumatized to form a standardized lesion, using bipolar
      cautery. A dose-response study was performed with 0.1, 0.3, 1 and 3 mg/kg/day
      rosiglitazone. Fifteen days later, adhesions were evaluated clinically and
      histopathologically. A time-response study was performed with 1 mg/kg/day
      rosiglitazone (the minimum dose found to significantly affect adhesion
      formation). Rosiglitazone was given for 7 days post-operatively and results were
      compared with those of control and the 15-day group (time-response). In all these
      studies, rosiglitazone was orally administered 3 days before the operation and
      continued post-operatively. In two further experimental groups, rosiglitazone was
      only administered pre-operatively or post-operatively. RESULTS: Approximately 1
      mg/kg/day rosiglitazone was found to reduce adhesion scores both clinically and
      histopathologically. Duration of treatment was also found to affect the extent of
      adhesion formation. However, giving rosiglitazone either just pre-operatively or
      post-operatively did not significantly reduce adhesion formation. CONCLUSION:
      Rosiglitazone with peroxisome proliferator-activated receptor (PPAR)-gamma
      agonist activity reduced the formation of i.p. adhesion possibly by reducing the
      initial inflammatory response and the subsequent exudation in this study.

PMID- 16997938
TI  - Investigation of the effects of heparin and low molecular weight heparin on E
      cadherin and laminin expression in rat pregnancy by immunohistochemistry.
AB  - BACKGROUND: Heparin and low molecular weight heparin (LMWH) are used widely to
      improve the pregnancy outcome in women with thrombophilia, miscarriage, recurrent
      miscarriage and fetal death. This study was designed to investigate the effects
      of heparin and LMWHs, enoxaparin and tinzaparin, on E-cadherin and laminin
      expression in placental and decidual tissues in rat pregnancy. METHODS: Wistar
      albino female rats (n = 48) were randomly assigned to four study groups (normal
      saline, heparin, enoxaparin and tinzaparin) in the preconceptional period. Tissue
      sections of placenta and decidua were immunohistochemically examined for the
      expression of E-cadherin and laminin. RESULTS: E-cadherin placental staining
      score of heparin group was significantly lower and E-cadherin decidual staining
      score of heparin and enoxaparin groups were significantly lower than control
      group. There were no significant differences in placental and decidual laminin
      staining scores among the study groups. CONCLUSIONS: Heparin and enoxaparin can
      reduce E-cadherin expression but not laminin expression in rat pregnancy. They
      might modulate trophoblast invasion. We suggest that this is the possible
      underlying mechanism involving in improvement of trophoblast invasion by the use
      of heparin and LMWH in patients with the history of miscarriage.

PMID- 16997939
TI  - The high mobility group box chromosomal protein 1 is expressed in the human and
      rat testis where it may function as an antibacterial factor.
AB  - BACKGROUND: The high mobility group box chromosomal protein 1 (HMGB1) was
      originally shown to be a nuclear DNA-binding protein that activates transcription
      and promotes differentiation. More recently, there have been reports that HMGB1
      may also function as a pro-inflammatory and antibacterial factor. The aim of this
      study was to investigate the testicular expression and antibacterial functions of
      HMGB1 to elucidate a possible role of HMGB1 in the testicular barrier defence
      against infections. METHODS AND RESULTS: RT-PCR and in situ hybridization
      revealed high-level testicular expression of HMGB1 mRNA and localization of this
      expression to the Sertoli cells and germ cells of the human and rat testis. In
      addition, immunohistochemical examination demonstrated the presence of the
      corresponding protein in Sertoli cells and spermatogonia in human and rat testes.
      Western blotting detected abundant amounts of the HMGB1 protein in the
      interstitial and intratubular fluids of the intact adult rat testis. Finally, the
      HMGB1 protein purified from both human and rat testis by reversed-phase high
      performance liquid chromatography (HPLC) exerted antibacterial activity towards
      Bacillus megaterium in an inhibition zone assay. CONCLUSION: HMGB1 is expressed
      by Sertoli cells and germ cells in the mammalian testis. In addition, purified
      testicular HMGB1 shows antibacterial activity, indicating that this protein may
      function as a paracrine host defence factor in the testis.

PMID- 16997940
TI  - Effect of chemo- or radiotherapy on sperm parameters of testicular cancer
      patients.
AB  - BACKGROUND: The aims of our study were to investigate the short- and long-term
      effects of chemo- or radiotherapy on spermatogenesis in patients with testicular
      cancer and to establish any correlation between pre-therapy sperm parameters,
      histotype and treatment type/intensity and the progress of spermatogenesis during
      the post-therapy period. METHODS: We evaluated 166 patients affected by
      testicular cancer, who cryobanked about 1 month after the removal of the
      cancerous testis and before beginning chemo- (CH group; n = 71) or radiotherapy
      (RT group; n = 95). RESULTS: For the CH group, there was a statistically
      significant decrease in sperm parameters, which was most significant 3 months
      after the end of chemotherapy. For the RT group, this decrease was most relevant
      6 months after the end of radiotherapy. Two years after therapy, 3% of the CH
      group and 6% of the RT group remained azoospermic. To evaluate whether
      spermatogenesis recovery is a function of baseline semen quality, we divided each
      group into two subgroups by pre-therapy total sperm count (A, <40 x
      10(6)/ejaculate; B, >or=40 x 10(6)/ejaculate). At t(24), subgroup A of both the
      CH and RT groups showed improved sperm parameters over the baseline, whereas
      subgroup B for both CH and RT groups showed a return of sperm parameters to those
      of baseline values. CONCLUSIONS: In conclusion, the recovery of spermatogenesis
      after chemo- or radiotherapy in our group of testicular cancer patients was not a
      function of pre-therapy sperm parameter quality. Cryopreservation of sperm before
      performing such therapy is therefore imperative.

PMID- 16997941
TI  - A randomized clinical trial of the effects of isosorbide mononitrate on bone
      formation and resorption in post-menopausal women: a pilot study.

PMID- 16997942
TI  - Possibility of hidden damages with temporary uterine artery occlusion device.

PMID- 16997943
TI  - Ethics and genetics of carrier embryos.

PMID- 16997944
TI  - Incorporating qualitative approaches is the path to adequate understanding of the
      psychosocial impact of polycystic ovary syndrome.

PMID- 16997945
TI  - Routine use of hysterosalpingography prior to diagnostic laparoscopy in the
      fertility workup.

PMID- 16997946
TI  - Global map of growth-regulated gene expression in Burkholderia pseudomallei, the
      causative agent of melioidosis.
AB  - Many microbial pathogens express specific virulence traits at distinct growth
      phases. To understand the molecular pathways linking bacterial growth to
      pathogenicity, we have characterized the growth transcriptome of Burkholderia
      pseudomallei, the causative agent of melioidosis. Using a fine-scale sampling
      approach, we found approximately 17% of all B. pseudomallei genes displaying
      regulated expression during growth in rich medium, occurring as broad waves of
      functionally coherent gene expression tightly associated with distinct growth
      phases and transition points. We observed regulation of virulence genes across
      all growth phases and identified serC as a potentially new virulence factor by
      virtue of its coexpression with other early-phase virulence genes. serC-disrupted
      B. pseudomallei strains were serine auxotrophs and in mouse infection assays
      exhibited a dramatic attenuation of virulence compared to wild-type B.
      pseudomallei. Immunization of mice with serC-disrupted B. pseudomallei also
      conferred protection against subsequent challenges with different wild-type B.
      pseudomallei strains. At a genomic level, early-phase genes were preferentially
      localized on chromosome 1, while stationary-phase genes were significantly biased
      towards chromosome 2. We detected a significant level of chromosomally clustered
      gene expression, allowing us to predict approximately 100 potential operons in
      the B. pseudomallei genome. We computationally and experimentally validated these
      operons by showing that genes in these regions are preferentially transcribed in
      the same 5'-->3' direction, possess significantly shorter intergenic lengths than
      the overall genome, and are expressed as a common mRNA transcript. The
      availability of this transcriptome map provides an important resource for
      understanding the transcriptional architecture of B. pseudomallei.

PMID- 16997947
TI  - Bacterial postgenomics: the promise and peril of systems biology.

PMID- 16997948
TI  - Characterization of myo-inositol utilization by Corynebacterium glutamicum: the
      stimulon, identification of transporters, and influence on L-lysine formation.
AB  - Although numerous bacteria possess genes annotated iol in their genomes, there
      have been very few studies on the possibly associated myo-inositol metabolism and
      its significance for the cell. We found that Corynebacterium glutamicum utilizes
      myo-inositol as a carbon and energy source, enabling proliferation with a high
      maximum rate of 0.35 h-1. Whole-genome DNA microarray analysis revealed that 31
      genes respond to myo-inositol utilization, with 21 of them being localized in two
      clusters of >14 kb. A set of genomic mutations and functional studies yielded the
      result that some genes in the two clusters are redundant, and only cluster I is
      necessary for catabolizing the polyol. There are three genes which encode
      carriers belonging to the major facilitator superfamily and which exhibit a >12
      fold increased mRNA level on myo-inositol. As revealed by mutant
      characterizations, one carrier is not involved in myo-inositol uptake whereas the
      other two are active and can completely replace each other with apparent Kms for
      myo-inositol as a substrate of 0.20 mM and 0.45 mM, respectively. Interestingly,
      upon utilization of myo-inositol, the L-lysine yield is 0.10 mol/mol, as opposed
      to 0.30 mol/mol, with glucose as the substrate. This is probably not only due to
      myo-inositol metabolism alone since a mixture of 187 mM glucose and 17 mM myo
      inositol, where the polyol only contributes 8% of the total carbon, reduced the L
      lysine yield by 29%. Moreover, genome comparisons with other bacteria highlight
      the core genes required for growth on myo-inositol, whose metabolism is still
      weakly defined.

PMID- 16997949
TI  - DNA adenine methylation regulates virulence gene expression in Salmonella
      enterica serovar Typhimurium.
AB  - Transcriptomic analyses during growth in Luria-Bertani medium were performed in
      strain SL1344 of Salmonella enterica serovar Typhimurium and in two isogenic
      derivatives lacking Dam methylase. More genes were repressed than were activated
      by Dam methylation (139 versus 37). Key genes that were differentially regulated
      by Dam methylation were verified independently. The largest classes of Dam
      repressed genes included genes belonging to the SOS regulon, as previously
      described in Escherichia coli, and genes of the SOS-inducible Salmonella
      prophages ST64B, Gifsy-1, and Fels-2. Dam-dependent virulence-related genes were
      also identified. Invasion genes in pathogenicity island SPI-1 were activated by
      Dam methylation, while the fimbrial operon std was repressed by Dam methylation.
      Certain flagellar genes were repressed by Dam methylation, and Dam(-) mutants of
      S. enterica showed reduced motility. Altered expression patterns in the absence
      of Dam methylation were also found for the chemotaxis genes cheR (repressed by
      Dam) and STM3216 (activated by Dam) and for the Braun lipoprotein gene, lppB
      (activated by Dam). The requirement for DNA adenine methylation in the regulation
      of specific virulence genes suggests that certain defects of Salmonella Dam(-)
      mutants in the mouse model may be caused by altered patterns of gene expression.

PMID- 16997950
TI  - Two gene determinants are differentially involved in the biogenesis of Fap1
      precursors in Streptococcus parasanguis.
AB  - Mature Fap1, a 200-kDa fimbria-associated adhesin, is required for fimbrial
      biogenesis and biofilm formation in Streptococcus parasanguis. Fap1-like proteins
      are found in the genomes of many streptococcal and staphylococcal species. Fap1
      is a serine-rich glycoprotein modified by O-linked glycan moieties. In this
      study, we identified a seven-gene cluster including secY2, orf1, orf2, orf3,
      secA2, gtf1, and gtf2 that is localized immediately downstream of fap1. The lower
      G+C contents and the presence of a putative transposase element suggest that this
      gene cluster was horizontally transferred from other bacteria and represents a
      genomic island. At least two genes in this island mediated Fap1 biogenesis.
      Mutation of a glucosyltransferase (Gtf1) gene led to accumulation of a Fap1
      precursor, which had no detectable glycan moieties. Inactivation of a gene coding
      for an accessory Sec protein (SecY2) resulted in expression of a distinct Fap1
      precursor, which reacted with one glycan-specific Fap1 antibody but not with
      another glycan-specific antibody. Furthermore, partially glycosylated Fap1 was
      detected on the cell surface and in the culture supernatant. These data suggest
      that SecY2 has a role in complete glycosylation of Fap1 and imply that SecY2 is
      not the only translocation channel for the Fap1 precursor and that alternative
      secretion machinery exists. Together, Gtf1 and SecY2 are involved in biogenesis
      of two distinct Fap1 precursors in S. parasanguis. Discovery of the effect of an
      accessory Sec protein on Fap1 glycosylation suggests that Fap1 secretion and
      glycosylation are coupled during Fap1 biogenesis.

PMID- 16997951
TI  - Identification of non-dot/icm suppressors of the Legionella pneumophila DeltadotL
      lethality phenotype.
AB  - Legionella pneumophila, a causative agent of bacterial pneumonia, survives inside
      phagocytic cells by avoiding rapid targeting to the lysosome. This bacterium
      utilizes a type IVB secretion system, encoded by the dot/icm genes, to replicate
      inside host cells. DotL, a critical component of the Dot/Icm secretion apparatus,
      functions as the type IV coupling protein. In contrast to most dot/icm genes,
      which are dispensable for growth on bacteriological media, dotL is required for
      the viability of wild-type L. pneumophila. Previously we reported that DeltadotL
      lethality could be suppressed by inactivation of the Dot/Icm complex via
      mutations in other dot/icm genes. Here we report the isolation of non-dot/icm
      suppressors of this phenotype. These DeltadotL suppressors include insertions
      that disrupt the function of the L. pneumophila homologs of cpxR, djlA, lysS, and
      two novel open reading frames, lpg0742 and lpg1594, that we have named ldsA and
      ldsB for lethality of DeltadotL suppressor. In addition to suppressing DeltadotL
      lethality, inactivation of these genes in a wild-type strain background causes a
      range of defects in L. pneumophila virulence traits, including intracellular
      growth, implicating these factors in the proper function of the Dot/Icm complex.
      Consistent with previous data showing a role for the cpx system in regulating
      expression of several dot/icm genes, the cpxR insertion mutant produced decreased
      levels of three Dot/Icm proteins, DotA, IcmV, and IcmW. The remaining four
      suppressors did not affect the steady-state levels of any Dot/Icm protein and are
      likely to represent the first identified factors necessary for assembly and/or
      activation of the Dot/Icm secretion complex.

PMID- 16997953
TI  - CbgA, a protein involved in cortex formation and stress resistance in Myxococcus
      xanthus spores.
AB  - CbgA plays a role in cortex formation and the acquisition of a subset of stress
      resistance properties in Myxococcus xanthus spores. The cbgA mutant produces
      spores with thin or no cortex layers, and these spores are more sensitive to heat
      and sodium dodecyl sulfate than their wild-type counterparts.

PMID- 16997952
TI  - Structural and functional conversion of molecular chaperone ClpB from the gram
      positive halophilic lactic acid bacterium Tetragenococcus halophilus mediated by
      ATP and stress.
AB  - In this study, we report the purification, initial structural characterization,
      and functional analysis of the molecular chaperone ClpB from the gram-positive,
      halophilic lactic acid bacterium Tetragenococcus halophilus. A recombinant T.
      halophilus ClpB (ClpB(Tha)) was overexpressed in Escherichia coli and purified by
      affinity chromatography, hydroxyapatite chromatography, and gel filtration
      chromatography. As demonstrated by gel filtration chromatography, chemical cross
      linking with glutaraldehyde, and electron microscopy, ClpB(Tha) forms a
      homohexameric single-ring structure in the presence of ATP under nonstress
      conditions. However, under stress conditions, such as high-temperature (>45
      degrees C) and high-salt concentrations (>1 M KCl), it dissociated into dimers
      and monomers, regardless of the presence of ATP. The hexameric ClpB(Tha)
      reactivated heat-aggregated proteins dependent upon the DnaK system from T.
      halophilus (KJE(Tha)) and ATP. Interestingly, the mixture of dimer and monomer
      ClpB(Tha), which was formed under stress conditions, protected substrate proteins
      from thermal inactivation and aggregation in a manner similar to those of general
      molecular chaperones. From these results, we hypothesize that ClpB(Tha) forms
      dimers and monomers to function as a holding chaperone under stress conditions,
      whereas it forms a hexamer ring to function as a disaggregating chaperone in
      cooperation with KJE(Tha) and ATP under poststress conditions.

PMID- 16997954
TI  - Evidence for recombination in Mycobacterium tuberculosis.
AB  - Due to its mostly isolated living environment, Mycobacterium tuberculosis is
      generally believed to be highly clonal, and thus recombination between different
      strains must be rare and is not critical for the survival of the species. To
      investigate the roles recombination could have possibly played in the evolution
      of M. tuberculosis, an analysis was conducted on previously determined genotypes
      of 36 synonymous single nucleotide polymorphisms (SNPs) in 3,320 M. tuberculosis
      isolates. The results confirmed the predominant clonal structure of the M.
      tuberculosis population. However, recombination between different strains was
      also suggested. To further resolve the issue, 175 intergenic SNPs and 234
      synonymous SNPs were genotyped in 37 selected representative strains. A clear
      mosaic polymorphic pattern ahead of the MT0105 locus encoding a PPE (Pro-Pro-Glu)
      protein was obtained, which is most likely a result of recombination hot spot.
      Given that PPE proteins are thought to be critical in host-pathogen interactions,
      we hypothesize that recombination has been influential in the history of M.
      tuberculosis and possibly a major contributor to the diversity observed ahead of
      the MT0105 locus.

PMID- 16997955
TI  - Detection of protein-protein interactions in the alkanesulfonate monooxygenase
      system from Escherichia coli.
AB  - The two-component alkanesulfonate monooxygenase system utilizes reduced flavin as
      a substrate to catalyze a unique desulfonation reaction during times of sulfur
      starvation. The importance of protein-protein interactions in the mechanism of
      flavin transfer was analyzed in these studies. The results from affinity
      chromatography and cross-linking experiments support the formation of a stable
      complex between the flavin mononucleotide (FMN) reductase (SsuE) and
      monooxygenase (SsuD). Interactions between the two proteins do not lead to
      overall conformational changes in protein structure, as indicated by the results
      from circular dichroism spectroscopy in the far-UV region. However, subtle
      changes in the flavin environment of FMN-bound SsuE that occur in the presence of
      SsuD were identified by circular dichroism spectroscopy in the visible region.
      These data are supported by the results from fluorescent spectroscopy
      experiments, where a dissociation constant of 0.0022 +/- 0.0010 muM was obtained
      for the binding of SsuE to SsuD. Based on these studies, the stoichiometry for
      protein-protein interactions is proposed to involve a 1:1 monomeric association
      of SsuE with SsuD.

PMID- 16997956
TI  - Regulation of sulfur assimilation pathways in Burkholderia cenocepacia:
      identification of transcription factors CysB and SsuR and their role in control
      of target genes.
AB  - Two genes encoding transcriptional regulators involved in sulfur assimilation
      pathways in Burkholderia cenocepacia strain 715j have been identified and
      characterized functionally. Knockout mutations in each of the B. cenocepacia
      genes were constructed and introduced into the genome of 715j by allelic
      replacement. Studies on the utilization of various sulfur sources by 715j and the
      obtained mutants demonstrated that one of the B. cenocepacia regulators,
      designated CysB, is preferentially involved in the control of sulfate transport
      and reduction, while the other, designated SsuR, is required for aliphatic
      sulfonate utilization. Using transcriptional promoter-lacZ fusions and DNA
      binding experiments, we identified several target promoters for positive control
      by CysB and/or SsuR--sbpp (preceding the sbp cysT cysW cysA ssuR cluster), cysIp
      (preceding the cysI cysD1 cysN cysH cysG cluster), cysD2p (preceding a separate
      cluster, cysD2 cysNC), and ssuDp (located upstream of the ssuDCB operon)--and we
      demonstrated overlapping functions of CysB and SsuR at particular promoters. We
      also demonstrated that the cysB gene is negatively controlled by both CysB and
      SsuR but the ssuR gene itself is not significantly regulated as a separate
      transcription unit. The function of B. cenocepacia CysB (in vivo and in vitro)
      appeared to be independent of the presence of acetylserine, the indispensable
      coinducer of the CysB regulators of Escherichia coli and Salmonella. The
      phylogenetic relationships among members of the "CysB family" in the gamma and
      beta subphyla are presented.

PMID- 16997957
TI  - Pip, a novel activator of phenazine biosynthesis in Pseudomonas chlororaphis
      PCL1391.
AB  - Secondary metabolites are important factors for interactions between bacteria and
      other organisms. Pseudomonas chlororaphis PCL1391 produces the antifungal
      secondary metabolite phenazine-1-carboxamide (PCN) that inhibits growth of
      Fusarium oxysporum f. sp. radius lycopersici the causative agent of tomato foot
      and root rot. Our previous work unraveled a cascade of genes regulating the PCN
      biosynthesis operon, phzABCDEFGH. Via a genetic screen, we identify in this study
      a novel TetR/AcrR regulator, named Pip (phenazine inducing protein), which is
      essential for PCN biosynthesis. A combination of a phenotypical characterization
      of a pip mutant, in trans complementation assays of various mutant strains, and
      electrophoretic mobility shift assays identified Pip as the fifth DNA-binding
      protein so far involved in regulation of PCN biosynthesis. In this regulatory
      pathway, Pip is positioned downstream of PsrA (Pseudomonas sigma factor
      regulator) and the stationary-phase sigma factor RpoS, while it is upstream of
      the quorum-sensing system PhzI/PhzR. These findings provide further evidence that
      the path leading to the expression of secondary metabolism gene clusters in
      Pseudomonas species is highly complex.

PMID- 16997958
TI  - Molecular characterization of the minimal replicon and the unidirectional theta
      replication of pSCM201 in extremely halophilic archaea.
AB  - A 3,463-bp plasmid, pSCM201, was isolated from a halophilic archaeon, Haloarcula
      sp. strain AS7094. The minimal replicon that is essential and sufficient for
      autonomous replication and stable maintenance in Haloarcula hispanica was
      determined by deletion analysis of the plasmid. This minimal replicon (
      approximately 1.8 kb) consisted of only two functionally related segments: (i) a
      putative origin (ori201) containing an AT-rich region and sets of repeats and
      (ii) an adjacent gene encoding a putative replication initiation protein
      (Rep201). Electron microscopic observation and Southern blotting analysis
      demonstrated that pSCM201 replicates via a theta mechanism. Precise mapping of
      the putative origin suggested that the replication initiated from a fixed site
      close to the AT-rich region and proceeded unidirectionally toward the downstream
      rep201 gene, which was further confirmed by electron microscopic analysis of the
      ClaI-digested replication intermediates. To our knowledge, this is the first
      unidirectional theta replication plasmid experimentally identified in the domain
      of archaea. It provides a novel plasmid system to conduct research on archaeal
      DNA replication.

PMID- 16997959
TI  - The cation-responsive protein NhaR of Escherichia coli activates pgaABCD
      transcription, required for production of the biofilm adhesin poly-beta-1,6-N
      acetyl-D-glucosamine.
AB  - The pgaABCD operon of Escherichia coli is required for production of the biofilm
      adhesin poly-beta-1,6-N-acetyl-d-glucosamine (PGA). We establish here that NhaR,
      a DNA-binding protein of the LysR family of transcriptional regulators, activates
      transcription of this operon. Disruption of the nhaR gene decreased biofilm
      formation without affecting planktonic growth. PGA production was undetectable in
      an nhaR mutant strain. Expression of a pgaA'-'lacZ translational fusion was
      induced by NaCl and alkaline pH, but not by CaCl(2) or sucrose, in an nhaR
      dependent fashion. Primer extension and quantitative real-time reverse
      transcription-PCR analyses further revealed that NhaR affects the steady-state
      level of pga mRNA. A purified recombinant NhaR protein bound specifically and
      with high affinity within the pgaABCD promoter region; one apparent binding site
      overlaps the -35 element, and a second site lies immediately upstream of the
      first. This protein was necessary and sufficient for activation of in vitro
      transcription from the pgaA promoter. These results define a novel mechanism for
      regulation of biofilm formation in response to environmental conditions and
      suggest an expanded role for NhaR in promoting bacterial survival.

PMID- 16997960
TI  - Mutation in a "tesB-like" hydroxyacyl-coenzyme A-specific thioesterase gene
      causes hyperproduction of extracellular polyhydroxyalkanoates by Alcanivorax
      borkumensis SK2.
AB  - A novel mutant of the marine oil-degrading bacterium Alcanivorax borkumensis SK2,
      containing a mini-Tn5 transposon disrupting a "tesB-like" acyl-coenzyme A (CoA)
      thioesterase gene, was found to hyperproduce polyhydroxyalkanoates (PHA),
      resulting in the extracellular deposition of this biotechnologically important
      polymer when grown on alkanes. The tesB-like gene encodes a distinct novel enzyme
      activity, which acts exclusively on hydroxylated acyl-CoAs and thus represents a
      hydroxyacyl-CoA-specific thioesterase. Inactivation of this enzyme results in the
      rechanneling of CoA-activated hydroxylated fatty acids, the cellular
      intermediates of alkane degradation, towards PHA production. These findings may
      open up new avenues for the development of simplified biotechnological processes
      for the production of PHA as a raw material for the production of bioplastics.

PMID- 16997961
TI  - Role of bacteriocin immunity proteins in the antimicrobial sensitivity of
      Streptococcus mutans.
AB  - Bacteria utilize quorum-sensing systems to modulate environmental stress
      responses. The quorum-sensing system of Streptococcus mutans is mediated by the
      competence-stimulating peptide (CSP), whose precursor is encoded by the comC
      gene. A comC mutant of strain GS5 exhibited enhanced antimicrobial sensitivity to
      a wide variety of different agents. Since the addition of exogenous CSP did not
      complement this phenotype, it was determined that the increased tetracycline,
      penicillin, and triclosan sensitivities resulted from repression of the putative
      bacteriocin immunity protein gene, bip, which is located immediately upstream
      from comC. We further demonstrated that the inactivation of bip or smbG, another
      bacteriocin immunity protein gene present within the smb operon in S. mutans GS5,
      affected sensitivity to a variety of antimicrobial agents. Furthermore, both the
      bip and smbG genes were upregulated in the presence of low concentrations of
      antibiotics and were induced during biofilm formation relative to in planktonic
      cells. These results suggest, for the first time, that the antimicrobial
      sensitivity of a bacterium can be modulated by some of the putative bacteriocin
      immunity proteins expressed by the organism. The implications of these
      observations for the evolution of bacteriocin immunity protein genes as well as
      for potential new chemotherapeutic strategies are discussed.

PMID- 16997962
TI  - CovR activation of the dipeptide permease promoter (PdppA) in Group A
      Streptococcus.
AB  - CovR, the two-component response regulator of Streptococcus pyogenes (group A
      streptococcus [GAS]) directly or indirectly represses about 15% of the genome,
      including genes encoding many virulence factors and itself. Transcriptome
      analyses also showed that some genes are activated by CovR. We asked whether the
      regulation by CovR of one of these genes, dppA, the first gene in an operon
      encoding a dipeptide permease, is direct or indirect. Direct regulation by CovR
      was suggested by the presence of five CovR consensus binding sequences (CBs) near
      the putative promoter. In this study, we identified the 5' end of the dppA
      transcript synthesized in vivo and showed that the start of dppA transcription in
      vitro is the same. We found that CovR binds specifically to the dppA promoter
      region (PdppA) in vitro with an affinity similar to that at which it binds to
      other CovR-regulated promoters. Disruption of any of the five CBs by a
      substitution of GG for TT inhibited CovR binding to that site in vitro, and
      binding at two of the CBs appeared cooperative. In vivo, CovR activation of
      transcription was not affected by individual mutations of any of the four CBs
      that we could study. This suggests that the binding sites are redundant in vivo.
      In vitro, CovR did not activate transcription from PdppA in experiments using
      purified GAS RNA polymerase and either linear or supercoiled DNA template.
      Therefore, we propose that in vivo, CovR may interfere with the binding of a
      repressor of PdppA.

PMID- 16997963
TI  - Conservation and divergence in cellulosome architecture between two strains of
      Ruminococcus flavefaciens.
AB  - A 17-kb scaffoldin gene cluster in Ruminococcus flavefaciens strain FD-1 was
      compared with the homologous segment published for strain 17. Although the
      general design of the cluster is identical in the two strains, significant
      differences in the modular architecture of the scaffoldin proteins were
      discovered, implying strain-specific divergence in cellulosome organization.

PMID- 16997964
TI  - Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin
      like lectins) on human leukocytes.
AB  - Group B Streptococcus (GBS) is classified into nine serotypes that vary in
      capsular polysaccharide (CPS) architecture but share in common the presence of a
      terminal sialic acid (Sia) residue. This position and linkage of GBS Sia closely
      resembles that of cell surface glycans found abundantly on human cells. CD33
      related Siglecs (CD33rSiglecs) are a family of Sia-binding lectins expressed on
      host leukocytes that engage host Sia-capped glycans and send signals that dampen
      inflammatory gene activation. We hypothesized that GBS evolved to display CPS Sia
      as a form of molecular mimicry limiting the activation of an effective innate
      immune response. In this study, we applied a panel of immunologic and cell-based
      assays to demonstrate that GBS of several serotypes interacts in a Sia- and
      serotype-specific manner with certain human CD33rSiglecs, including hSiglec-9 and
      hSiglec-5 expressed on neutrophils and monocytes. Modification of GBS CPS Sia by
      O acetylation has recently been recognized, and we further show that the degree
      of O acetylation can markedly affect the interaction between GBS and hSiglec-5, 
      7, and -9. Thus, production of Sia-capped bacterial polysaccharide capsules that
      mimic human cell surface glycans in order to engage CD33rSiglecs may be an
      example of a previously unrecognized bacterial mechanism of leukocyte
      manipulation.

PMID- 16997965
TI  - A member of the second carbohydrate uptake subfamily of ATP-binding cassette
      transporters is responsible for ribonucleoside uptake in Streptococcus mutans.
AB  - Streptococcus mutans has a significant number of transporters of the ATP-binding
      cassette (ABC) superfamily. Members of this superfamily are involved in the
      translocation of a diverse range of molecules across membranes. However, the
      functions of many of these members remain unknown. We have investigated the role
      of the single S. mutans representative of the second subfamily of carbohydrate
      uptake transporters (CUT2) of the ABC superfamily. The genetic context of genes
      encoding this transporter indicates that it may have a role in ribonucleoside
      scavenging. Inactivation of rnsA (ATPase) or rnsB (solute binding protein)
      resulted in strains resistant to 5-fluorocytidine and 5-fluorouridine (toxic
      ribonucleoside analogues). As other ribonucleosides including cytidine, uridine,
      adenosine, 2-deoxyuridine, and 2-deoxycytidine protected S. mutans from 5
      fluorocytidine and 5-fluorouridine toxicity, it is likely that this transporter
      is involved in the uptake of these molecules. Indeed, the rnsA and rnsB mutants
      were unable to transport [2-(14)C]cytidine or [2-(14)C]uridine and had
      significantly reduced [8-(14)C]adenosine uptake rates. Characterization of this
      transporter in wild-type S. mutans indicates that it is a high-affinity (K(m) = 1
      to 2 muM) transporter of cytidine, uridine, and adenosine. The inhibition of
      [(14)C]cytidine uptake by a range of structurally related molecules indicates
      that the CUT2 transporter is involved in the uptake of most ribonucleosides,
      including 2-deoxyribonucleosides, but not ribose or nucleobases. The
      characterization of this permease has directly shown for the first time that an
      ABC transporter is involved in the uptake of ribonucleosides and extends the
      range of substrates known to be transported by members of the ABC transporter
      superfamily.

PMID- 16997966
TI  - Characterization of 2-bromoethanesulfonate as a selective inhibitor of the
      coenzyme m-dependent pathway and enzymes of bacterial aliphatic epoxide
      metabolism.
AB  - Bacterial growth with short-chain aliphatic alkenes requires coenzyme M (CoM) (2
      mercaptoethanesulfonic acid), which serves as the nucleophile for activation and
      conversion of epoxide products formed from alkene oxidation to central
      metabolites. In the present work the CoM analog 2-bromoethanesulfonate (BES) was
      shown to be a specific inhibitor of propylene-dependent growth of and
      epoxypropane metabolism by Xanthobacter autotrophicus strain Py2. BES (at low
      [millimolar] concentrations) completely prevented growth with propylene but had
      no effect on growth with acetone or n-propanol. Propylene consumption by cells
      was largely unaffected by the presence of BES, but epoxypropane accumulated in
      the medium in a time-dependent fashion with BES present. The addition of BES to
      cells resulted in time-dependent loss of epoxypropane degradation activity that
      was restored upon removal of BES and addition of CoM. Exposure of cells to BES
      resulted in a loss of epoxypropane-dependent CO(2) fixation activity that was
      restored only upon synthesis of new protein. Addition of BES to cell extracts
      resulted in an irreversible loss of epoxide carboxylase activity that was
      restored by addition of purified 2-ketopropyl-CoM carboxylase/oxidoreductase (2
      KPCC), the terminal enzyme of epoxide carboxylation, but not by addition of
      epoxyalkane:CoM transferase or 2-hydroxypropyl-CoM dehydrogenase, the enzymes
      which catalyze the first two reactions of epoxide carboxylation. Comparative
      studies of the propylene-oxidizing actinomycete Rhodococcus rhodochrous strain
      B276 showed that BES is an inhibitor of propylene-dependent growth in this
      organism as well but is not an inhibitor of CoM-independent growth with propane.
      These results suggest that BES inhibits propylene-dependent growth and epoxide
      metabolism via irreversible inactivation of the key CO(2)-fixing enzyme 2-KPCC.

PMID- 16997967
TI  - YtxR, a conserved LysR-like regulator that induces expression of genes encoding a
      putative ADP-ribosyltransferase toxin homologue in Yersinia enterocolitica.
AB  - Yersinia enterocolitica causes human gastroenteritis, and many isolates have been
      classified as either "American" or "non-American" strains based on their
      geographic prevalence and virulence properties. In this study we describe
      identification of a transcriptional regulator that controls expression of the Y.
      enterocolitica ytxAB genes. The ytxAB genes have the potential to encode an ADP
      ribosylating toxin with similarity to pertussis toxin. However, a ytxAB null
      mutation did not affect virulence in mice. Nevertheless, the ytxAB genes are
      conserved in many Y. enterocolitica strains. Interestingly, American and non
      American strains have different ytxAB alleles encoding proteins that are only 50
      to 60% identical. To obtain further insight into the ytxAB locus, we investigated
      whether it is regulated as part of a known or novel regulon. Transposon
      mutagenesis identified a LysR-like regulator, which we designated YtxR.
      Expression of ytxR from a nonnative promoter increased Phi(ytxA-lacZ) operon
      fusion expression up to 35-fold. YtxR also activated expression of its own
      promoter. DNase I footprinting showed that a His(6)-YtxR fusion protein directly
      interacted with the ytxA and ytxR control regions at similar distances upstream
      of their probable transcription initiation sites, identified by primer extension.
      Deletion analysis demonstrated that removal of the regions protected by His(6)
      YtxR in vitro eliminated YtxR-dependent induction in vivo. The ytxAB locus is not
      present in most Yersinia species. In contrast, ytxR is conserved in multiple
      Yersinia species, as well as in the closely related organisms Photorhabdus
      luminescens and Photorhabdus asymbiotica. These observations suggest that YtxR
      may play a conserved role involving regulation of other genes besides ytxAB.

PMID- 16997968
TI  - Multiple GTPases participate in the assembly of the large ribosomal subunit in
      Bacillus subtilis.
AB  - GTPases have been demonstrated to be necessary for the proper assembly of the
      ribosome in bacteria and eukaryotes. Here, we show that the essential GTPases
      YphC and YsxC are required for large ribosomal subunit biogenesis in Bacillus
      subtilis. Sucrose density gradient centrifugation of large ribosomal subunits
      isolated from YphC-depleted cells and YsxC-depleted cells indicates that they are
      similar to the 45S intermediate previously identified in RbgA-depleted cells. The
      sedimentation of the large-subunit intermediate isolated from YphC-depleted cells
      was identical to the intermediate found in RbgA-depleted cells, while the
      intermediate isolated from YsxC-depleted cells sedimented slightly slower than
      45S, suggesting that it is a novel intermediate. Analysis of the protein
      composition of the large-subunit intermediates isolated from either YphC-depleted
      cells or YsxC-depleted cells indicated that L16 and L36 are missing. Purified
      YphC and YsxC are able to interact with the ribosome in vitro, supporting a
      direct role for these two proteins in the assembly of the 50S subunit. Our
      results indicate that, as has been demonstrated for Saccharomyces cerevisiae
      ribosome biogenesis, bacterial 50S ribosome assembly requires the function of
      multiple essential GTPases.

PMID- 16997969
TI  - Crystal structure and mechanism of TraM2, a second quorum-sensing antiactivator
      of Agrobacterium tumefaciens strain A6.
AB  - Quorum sensing is a community behavior that bacteria utilize to coordinate a
      variety of population density-dependent biological functions. In Agrobacterium
      tumefaciens, quorum sensing regulates the replication and conjugative transfer of
      the tumor-inducing (Ti) plasmid from pathogenic strains to nonpathogenic
      derivatives. Most of the quorum-sensing regulatory proteins are encoded within
      the Ti plasmid. Among these, TraR is a LuxR-type transcription factor playing a
      key role as the quorum-sensing signal receptor, and TraM is an antiactivator that
      antagonizes TraR through the formation of a stable oligomeric complex. Recently,
      a second TraM homologue called TraM2, not encoded on the Ti plasmid of A.
      tumefaciens A6, was identified, in addition to a copy on the Ti plasmid. In this
      report, we have characterized TraM2 and its interaction with TraR and solved its
      crystal structure to 2.1 A. Like TraM, TraM2 folds into a helical bundle and
      exists as homodimer. TraM2 forms a stable complex (K(d) = 8.6 nM) with TraR in a
      1:1 binding ratio, a weaker affinity than that of TraM for TraR. Structural
      analysis and biochemical studies suggest that protein stability may account for
      the difference between TraM2 and TraM in their binding affinities to TraR and
      provide a structural basis for L54 in promoting structural stability of TraM.

PMID- 16997970
TI  - A Type Ib ParB protein involved in plasmid partitioning in a gram-positive
      bacterium.
AB  - Our current understanding of segregation of prokaryotic plasmids has been derived
      mainly from the study of the gram-negative bacterial plasmids. We previously
      reported a replicon of the cryptic plasmid from a gram-positive bacterium,
      Leifsonia xyli subsp. cynodontis. The replicon contains a putative plasmid
      partition cassette including a Walker-type ATPase followed by open reading frame
      4 without sequence homologue. Here we reported that the orf4 gene was essential
      for maintaining the plasmid stability in L. xyli subsp. cynodontis. Furthermore,
      the purified orf4 protein specifically and cooperatively bound to direct repeat
      sequences located upstream of the parA gene in vitro, indicating that orf4 is a
      parB gene and that the direct repeat DNA sequences constitute a partition site,
      parS. The location of parS and the features of ParA and ParB proteins suggest
      that this plasmid partition cassette belongs to type Ib, representing the first
      type Ib cassette identified from a gram-positive bacterial plasmid.

PMID- 16997971
TI  - In silico prediction and functional validation of sigma28-regulated genes in
      Chlamydia and Escherichia coli.
AB  - sigma(28) RNA polymerase is an alternative RNA polymerase that has been proposed
      to have a role in late developmental gene regulation in Chlamydia, but only a
      single target gene has been identified. To discover additional sigma(28)
      dependent genes in the Chlamydia trachomatis genome, we applied bioinformatic
      methods using a probability weight matrix based on known sigma(28) promoters in
      other bacteria and a second matrix based on a functional analysis of the
      sigma(28) promoter. We tested 16 candidate sigma(28) promoters predicted with
      these algorithms and found that 5 were active in a chlamydial sigma(28) in vitro
      transcription assay. hctB, the known sigma(28)-regulated gene, is only expressed
      late in the chlamydial developmental cycle only, and two of the newly identified
      sigma(28) target genes (tsp and tlyC_1) also have late expression profiles,
      providing support for sigma(28) as a regulator of late gene expression. One of
      the other novel sigma(28)-regulated genes is dnaK, a known heat shock-responsive
      gene, suggesting that sigma(28) RNA polymerase may be involved in the response to
      cellular stress. Our sigma(28) prediction algorithm can be applied to other
      bacteria, and by performing a similar analysis on the Escherichia coli genome, we
      have predicted and functionally identified five previously unknown sigma(28)
      regulated genes in E. coli.

PMID- 16997972
TI  - BOX elements modulate gene expression in Streptococcus pneumoniae: impact on the
      fine-tuning of competence development.
AB  - More than 100 BOX elements are randomly distributed in intergenic regions of the
      pneumococcal genome. Here we demonstrate that these elements can affect
      expression of neighboring genes and present evidence that they are mobile.
      Together, our findings show that BOX elements enhance genetic diversity and
      genomic plasticity in Streptococcus pneumoniae.

PMID- 16997973
TI  - Rapid broad-spectrum analgesia through activation of peroxisome proliferator
      activated receptor-alpha.
AB  - Severe pain remains a major area of unmet medical need. Here we report that
      agonists of the nuclear receptor PPAR-alpha (peroxisome proliferator-activated
      receptor-alpha) suppress pain behaviors induced in mice by chemical tissue
      injury, nerve damage, or inflammation. The PPAR-alpha agonists GW7647 [2-(4-(2-(1
      cyclohexanebutyl)-3-cyclohexylureido)ethyl)phenylthio)-2-methylpropionic acid],
      Wy-14643 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid], and
      palmitoylethanolamide (PEA) reduced nocifensive behaviors elicited in mice by
      intraplantar (i.pl.) injection of formalin or i.p. injection of magnesium
      sulfate. These effects were absent in PPAR-alpha-null mice yet occurred within
      minutes of agonist administration in wild-type mice, suggesting that they were
      mediated through a transcription-independent mechanism. Consistent with this
      hypothesis, blockade of calcium-operated IK(ca) (K(Ca)3.1) and BK(ca) (K(Ca)1.1)
      potassium channels prevented the effects of GW7647 and PEA in the formalin test.
      Three observations suggest that PPAR-alpha agonists may inhibit nocifensive
      responses by acting on peripheral PPAR-alpha. (i) PEA reduced formalin-induced
      pain at i.pl. doses that produced no increase in systemic PEA levels; (ii) PPAR
      alpha was expressed in dorsal root ganglia neurons of wild-type but not PPAR
      alpha-null mice; and (ii) GW7647 and PEA prevented formalin-induced firing of
      spinal cord nociceptive neurons in rats. In addition to modulating nociception,
      GW7647 and PEA reduced hyperalgesic responses in the chronic constriction injury
      model of neuropathic pain; these effects were also contingent on PPAR-alpha
      expression and were observed following either acute or subchronic PPAR-alpha
      agonist administration. Finally, acute administration of GW7647 and PEA reduced
      hyperalgesic responses in the complete Freund's adjuvant and carrageenan models
      of inflammatory pain. Our results suggest that PPAR-alpha agonists may represent
      a novel class of analgesics.

PMID- 16997974
TI  - Differential effects of systemic ethanol administration on protein kinase
      cepsilon, gamma, and beta isoform expression, membrane translocation, and target
      phosphorylation: reversal by chronic ethanol exposure.
AB  - Systemic ethanol administration alters protein kinase C (PKC) activity in brain,
      but the effects of ethanol on the expression and translocation of specific
      isoforms are unknown. Rats were administered ethanol (2 g/kg i.p.) or saline and
      PKC levels were measured in the cytosolic and membrane fractions by Western blot
      analysis. PKCepsilon expression was increased in the cytosol and decreased in the
      membrane (P2) fraction of cerebral cortex at 10 min. At 60 min, expression of
      PKCepsilon in the P2 fraction was increased by 42.2 +/- 12%, but cytosolic levels
      were unchanged. In contrast, PKCgamma in the P2 fraction was decreased 32.7 +/-
      7% at 60 min but not at 10 min post-ethanol administration. PKCgamma levels in
      the cytosol were reduced at 10 min post-ethanol administration and unchanged at
      60 min. PKCbeta expression was increased 36 +/- 10 and 144 +/- 52% in the P2
      fraction both at 10 and 60 min post-ethanol administration, whereas cytosolic
      levels were unchanged. Serine phosphorylation of GABA(A) receptor beta-chain was
      reduced, and phosphorylation of N-methyl-d-aspartate receptor NR1 subunit was
      increased 60 min following ethanol administration. There was no effect of acute
      ethanol administration on PKC isoform levels in the hippocampus. Ethanol
      challenge did not alter PKC isoform expression in the P2 fraction of cerebral
      cortex following chronic ethanol administration. These findings suggest that
      acute ethanol administration alters PKC synthesis and translocation in an isoform
      and brain region specific manner that leads to alterations in serine
      phosphorylation of receptors. Furthermore, chronic ethanol administration
      prevents ethanol-induced alterations in PKC expression in the P2 fraction, where
      PKC interacts with ethanol-responsive ion channels.

PMID- 16997975
TI  - Metabolism of thioamides by Ralstonia pickettii TA.
AB  - Information on bacterial thioamide metabolism has focused on transformation of
      the antituberculosis drug ethionamide and related compounds by Mycobacterium
      tuberculosis. To study this metabolism more generally, a bacterium that grew
      using thioacetamide as the sole nitrogen source was isolated via enrichment
      culture. The bacterium was identified as Ralstonia pickettii and designated
      strain TA. Cells grown on thioacetamide also transformed other thioamide
      compounds. Transformation of the thioamides tested was dependent on oxygen.
      During thioamide degradation, sulfur was detected in the medium at the oxidation
      level of sulfite, further suggesting an oxygenase mechanism. R. pickettii TA did
      not grow on thiobenzamide as a nitrogen source, but resting cells converted
      thiobenzamide to benzamide, with thiobenzamide S-oxide and benzonitrile detected
      as intermediates. Thioacetamide S-oxide was detected as an intermediate during
      thioacetamide degradation, but the only accumulating metabolite of thioacetamide
      was identified as 3,5-dimethyl-1,2,4-thiadiazole, a compound shown to derive from
      spontaneous reaction of thioacetamide and oxygenated thioacetamide species. This
      dead-end metabolite accounted for only ca. 12% of the metabolized thioacetamide.
      Neither acetonitrile nor acetamide was detected during thioacetamide degradation,
      but R. pickettii grew on both compounds as nitrogen and carbon sources. It is
      proposed that R. pickettii TA degrades thioamides via a mechanism involving
      consecutive oxygenations of the thioamide sulfur atom.

PMID- 16997976
TI  - Synergistic inhibition of microbial sulfide production by combinations of the
      metabolic inhibitor nitrite and biocides.
AB  - MICs of six broad-spectrum biocides and two specific metabolic inhibitors and
      fractional inhibitory concentration indexes (FICIs) for controlling a sulfide
      producing consortium were determined. Nitrite was synergistic (FICI<1) with all
      but one biocide due to its specific inhibition of dissimilatory sulfite
      reductase. Hence, combining nitrite with biocides allows more efficient and cost
      effective control of sulfate-reducing bacteria.

PMID- 16997977
TI  - Isolation of two polyketide synthase gene fragments from the uncultured microbial
      symbiont of the marine bryozoan Bugula neritina.
AB  - "Candidatus Endobugula sertula," the uncultured microbial symbiont of the
      bryozoan Bugula neritina, produces ecologically and biomedically important
      polyketide metabolites called bryostatins. We isolated two gene fragments from B.
      neritina larvae that have high levels of similarity to polyketide synthase genes.
      These gene fragments are clearly associated with the symbiont and not with the
      host.

PMID- 16997979
TI  - Reconstitution of the myxothiazol biosynthetic gene cluster by Red/ET
      recombination and heterologous expression in Myxococcus xanthus.
AB  - Although many secondary metabolites exhibiting important pharmaceutical and
      agrochemical activities have been isolated from myxobacteria, most of these
      microorganisms remain difficult to handle genetically. To utilize their metabolic
      potential, heterologous expression methodologies are currently being developed.
      Here, the Red/ET recombination technology was used to perform all required gene
      cluster engineering steps in Escherichia coli prior to the transfer into the
      chromosome of the heterologous host. We describe the integration of the complete
      57-kbp myxothiazol biosynthetic gene cluster reconstituted from two cosmids from
      a cosmid library of the myxobacterium Stigmatella aurantiaca DW4-3/1 into the
      chromosome of the thus far best-characterized myxobacterium, Myxococcus xanthus,
      in one step. The successful integration and expression of the myxothiazol
      biosynthetic genes in M. xanthus results in the production of myxothiazol in
      yields comparable to the natural producer strain.

PMID- 16997978
TI  - Tvbgn3, a beta-1,6-glucanase from the biocontrol fungus Trichoderma virens, is
      involved in mycoparasitism and control of Pythium ultimum.
AB  - Even though beta-1,6-glucanases have been purified from several filamentous
      fungi, the physiological function has not been conclusively established for any
      species. In the present study, the role of Tvbgn3, a beta-1,6-glucanase from
      Trichoderma virens, was examined by comparison of wild-type (WT) and transformant
      strains in which Tvbgn3 was disrupted (GKO) or constitutively overexpressed
      (GOE). Gene expression analysis revealed induction of Tvbgn3 in the presence of
      host fungal cell walls, indicating regulation during mycoparasitism. Indeed,
      while deletion or overexpression of Tvbgn3 had no evident effect on growth and
      development, GOE and GKO strains showed an enhanced or reduced ability,
      respectively, to inhibit the growth of the plant pathogen Pythium ultimum
      compared to results with the WT. The relevance of this activity in the biocontrol
      ability of T. virens was confirmed in plant bioassays. Deletion of the gene
      resulted in levels of disease protection that were significantly reduced from WT
      levels, while GOE strains showed a significantly increased biocontrol capability.
      These results demonstrate the involvement of beta-1,6-glucanase in mycoparasitism
      and its relevance in the biocontrol activity of T. virens, opening a new avenue
      for biotechnological applications.

PMID- 16997980
TI  - Role of the ptsN gene product in catabolite repression of the Pseudomonas putida
      TOL toluene degradation pathway in chemostat cultures.
AB  - The Pseudomonas putida KT2440 TOL upper pathway is repressed under nonlimiting
      conditions in cells growing in chemostat with succinate as a carbon source. We
      show that the ptsN gene product IIA(Ntr) participates in this repression. Crc,
      involved in yeast extract-dependent repression in batch cultures, did not
      influence expression when cells were growing in a chemostat with succinate at
      maximum rate.

PMID- 16997981
TI  - New rapid and simple methods for detection of bacteria and determination of their
      antibiotic susceptibility by using phage mutants.
AB  - Three new methods applying a novel approach for rapid and simple detection of
      specific bacteria, based on plaque formation as the end point of the phage lytic
      cycle, are described. Different procedures were designed to ensure that the
      resulting plaques were derived only from infected target bacteria ("infectious
      centers"). (i) A pair of amber mutants that cannot form plaques at concentrations
      lower than their reversion rate underwent complementation in the tested bacteria;
      the number of plaques formed was proportional to the concentration of the
      bacteria that were coinfected by these phage mutants. (ii) UV-irradiated phages
      were recovered by photoreactivation and/or SOS repair mediated by target bacteria
      and plated on a recA uvrA bacterial lawn in the dark to avoid recovery of
      noninfecting phages. (iii) Pairs of temperature-sensitive mutants were allowed to
      coinfect their target bacteria at the permissive temperature, followed by
      incubation of the plates at the restrictive temperature to avoid phage infection
      of the host cells. This method allowed the omission of centrifuging and washing
      the infected cells. Only phages that recovered by recombination or
      complementation were able to form plaques. The detection limit was 1 to 10 living
      Salmonella or Escherichia coli O157 cells after 3 to 5 h. The antibiotic
      susceptibility of the target bacteria could also be determined in each of these
      procedures by preincubating the target bacteria with antibiotic prior to phage
      infection. Bacteria sensitive to the antibiotic lost the ability to form
      infectious centers.

PMID- 16997982
TI  - Fingerprinting of Campylobacter jejuni by using resolution-optimized binary gene
      targets derived from comparative genome hybridization studies.
AB  - The aim of this investigation was to exploit the vast comparative data generated
      by comparative genome hybridization (CGH) studies of Campylobacter jejuni in
      developing a genotyping method. We examined genes in C. jejuni that exhibit
      binary status (present or absent between strains) within known plasticity
      regions, in order to identify a minimal subset of gene targets that provide high
      resolution genetic fingerprints. Using CGH data from three studies as input,
      binary gene sets were identified with "Minimum SNPs" software. "Minimum SNPs"
      selects for the minimum number of targets required to obtain a predefined
      resolution, based on Simpson's index of diversity (D). After implementation of
      stringent criteria for gene presence/absence, eight binary genes were found that
      provided 100% resolution (D=1) of 20 C. jejuni strains. A real-time PCR assay was
      developed and tested on 181 C. jejuni and Campylobacter coli isolates, a subset
      of which have previously been characterized by multilocus sequence typing, flaA
      short variable region sequencing, and pulsed-field gel electrophoresis. In
      addition to the binary gene real-time PCR assay, we refined the seven-member
      single nucleotide polymorphism (SNP) real-time PCR assay previously described for
      C. jejuni and C. coli. By normalizing the SNP assay with the respective C. jejuni
      and C. coli ubiquitous genes, mapA and ceuE, the polymorphisms at each SNP could
      be determined without separate reactions for every polymorphism. We have
      developed and refined a rapid, highly discriminatory genotyping method for C.
      jejuni and C. coli that uses generic technology and is amenable to high
      throughput analyses.

PMID- 16997983
TI  - Constitutive delivery of bovine beta-lactoglobulin to the digestive tracts of
      gnotobiotic mice by engineered Lactobacillus casei.
AB  - The gut microbiota is critical for maturation of the immune system. Recent
      evidence suggests that early establishment of lactobacilli in the intestinal
      microbiota, during neonatal colonization or by probiotic supplementation, could
      prevent the development of allergic disorders. Postnatal maturation of the gut
      immune system with allergen-producing lactobacilli colonizing the digestive tract
      could then affect the development of further allergic sensitization. In this
      paper, we describe construction of a recombinant Lactobacillus casei strain that
      can constitutively deliver bovine beta-lactoglobulin (BLG), a major cow's milk
      allergen, to the guts of gnotobiotic mice. The blg gene was inserted into the L.
      casei chromosome downstream of an endogenous promoter. BLG production was
      improved by fusing the propeptide LEISSTCDA (LEISS) to the BLG mature moiety.
      This led to a 10-fold increase in LEISS-BLG production compared to the production
      obtained without the propeptide and also led to enhanced secretion corresponding
      to 5% of the total production. After inoculation into germfree C3H/HeN mice, the
      genetic stability of the recombinant strain and in vivo BLG production were
      confirmed for at least 10 weeks. BLG stimulation of spleen cells from mice
      monoassociated with the BLG-producing lactobacilli induced secretion of the Th1
      cytokine gamma interferon and, to a lesser extent, the Th2 cytokine interleukin
      5. No BLG-specific immunoglobulin G1 (IgG1), IgG2a, or IgA was detected in sera
      or in fecal samples. These results suggest that gut colonization with allergen
      producing lactobacilli could provide a useful model for studying the modulation
      of allergic disorders.

PMID- 16997984
TI  - Functional analysis of the twin-arginine translocation pathway in Corynebacterium
      glutamicum ATCC 13869.
AB  - Compared to those of other gram-positive bacteria, the genetic structure of the
      Corynebacterium glutamicum Tat system is unique in that it contains the tatE gene
      in addition to tatA, tatB, and tatC. The tatE homologue has been detected only in
      the genomes of gram-negative enterobacteria. To assess the function of the C.
      glutamicum Tat pathway, we cloned the tatA, tatB, tatC, and tatE genes from C.
      glutamicum ATCC 13869 and constructed mutants carrying deletions of each tat gene
      or of both the tatA and tatE genes. Using green fluorescent protein (GFP) fused
      with the twin-arginine signal peptide of the Escherichia coli TorA protein, we
      demonstrated that the minimal functional Tat system required TatA and TatC. TatA
      and TatE provide overlapping function. Unlike the TatB proteins from gram
      negative bacteria, C. glutamicum TatB was dispensable for Tat function, although
      it was required for maximal efficiency of secretion. The signal peptide sequence
      of the isomaltodextranase (IMD) of Arthrobacter globiformis contains a twin
      arginine motif. We showed that both IMD and GFP fused with the signal peptide of
      IMD were secreted via the C. glutamicum Tat pathway. These observations indicate
      that IMD is a bona fide Tat substrate and imply great potential of the C.
      glutamicum Tat system for industrial production of heterologous folded proteins.

PMID- 16997985
TI  - Construction of a reporter vector for the analysis of Bifidobacterium longum
      promoters.
AB  - In order to initiate studies on promoter activities in Bifidobacterium longum and
      to independently confirm transcriptional data generated by microarray
      experiments, we have constructed a versatile reporter plasmid based on a B.
      longum cryptic plasmid and the Escherichia coli gusA gene. The resulting plasmid,
      pMDY23, has been tested using three B. longum promoters.

PMID- 16997986
TI  - Induction of heavy-metal-transporting CPX-type ATPases during acid adaptation in
      Lactobacillus bulgaricus.
AB  - Lactobacillus bulgaricus is a lactic acid bacteria (LAB) that, through the
      production of lactic acid, gradually acidifies its environment during growth. In
      the course of this process, L. bulgaricus acquires an improved tolerance to
      acidity. A survey of the recently established genome sequence shows that this
      bacterium possesses few of the pH control functions that have been described in
      other LAB and raises the question of what other mechanisms could be involved in
      its adaptation to the decreasing environmental pH. In some bacteria other than
      LAB, ion transport systems have been implicated in acid adaptation. We therefore
      studied the expression of this type of transport system during acid adaptation in
      L. bulgaricus by reverse transcription and real-time quantitative PCR and mapped
      transcription start sites. Intriguingly, the most significantly induced were
      three ATPases carrying the CPX signature of heavy-metal transporters. Protein
      homology and the presence of a conserved sequence motif in the promoter regions
      of the genes encoding these proteins strongly suggest that they are involved in
      copper homeostasis. Induction of this system is thought to assist in avoiding
      indirect damage that could result from medium acidification.

PMID- 16997987
TI  - Disruption of N-acyl homoserine lactone-mediated cell signaling and iron
      acquisition in epiphytic bacteria by leaf surface compounds.
AB  - Since N-acyl homoserine lactones (AHLs) are key mediators of cell density
      dependent regulation of traits involved in virulence and epiphytic fitness in
      gram-negative bacteria such as Pseudomonas syringae, a variety of plant species
      were examined to determine their production of leaf surface compounds that could
      interact with these signaling systems. Leaf washings of 17 of 52 plant species
      tested stimulated or inhibited AHL-dependent traits in at least one of the
      bacterial reporter strains used. The active compounds from most plants could be
      distinguished from known AHLs due to different patterns of mobility during C8 and
      C18 reverse-phase thin-layer chromatography (TLC) and normal-phase TLC compared
      to the patterns for authentic bacterial AHLs. All plant extracts were also tested
      to determine their abilities to sequester iron and trigger bacterial siderophore
      synthesis on a medium containing abundant iron. Leaf washings from 16 of the 52
      plant species, as well as tannic acid solutions, stimulated pyoverdine synthesis
      in P. syringae in a high-iron medium. These preparations also inhibited the
      growth of a P. syringae mutant unable to produce pyoverdine siderophores but not
      the growth of the wild-type bacterium. The stimulation of siderophore production
      and the growth inhibition by plant extracts and purified tannins were both
      reversed by addition of ferric chloride to culture media, indicating that iron
      was made unavailable by the compounds released onto the leaf surface.

PMID- 16997988
TI  - Detection of human-derived fecal pollution in environmental waters by use of a
      PCR-based human polyomavirus assay.
AB  - Regulatory agencies mandate the use of fecal coliforms, Escherichia coli or
      Enterococcus spp., as microbial indicators of recreational water quality. These
      indicators of fecal pollution do not identify the specific sources of pollution
      and at times underestimate health risks associated with recreational water use.
      This study proposes the use of human polyomaviruses (HPyVs), which are widespread
      among human populations, as indicators of human fecal pollution. A method was
      developed to concentrate and extract HPyV DNA from environmental water samples
      and then to amplify it by nested PCR. HPyVs were detected in as little as 1
      microl of sewage and were not amplified from dairy cow or pig wastes.
      Environmental water samples were screened for the presence of HPyVs and two
      additional markers of human fecal pollution: the Enterococcus faecium esp gene
      and the 16S rRNA gene of human-associated Bacteroides. The presence of human
      specific indicators of fecal pollution was compared to fecal coliform and
      Enterococcus concentrations. HPyVs were detected in 19 of 20 (95%) samples
      containing the E. faecium esp gene and Bacteroides human markers. Weak or no
      correlation was observed between the presence/absence of human-associated
      indicators and counts of indicator bacteria. The sensitivity, specificity, and
      correlation with other human-associated markers suggest that the HPyV assay could
      be a useful predictor of human fecal pollution in environmental waters and an
      important component of the microbial-source-tracking "toolbox."

PMID- 16997989
TI  - Role of quorum sensing and antimicrobial component production by Serratia
      plymuthica in formation of biofilms, including mixed biofilms with Escherichia
      coli.
AB  - We have previously characterized the N-acyl-l-homoserine lactone-based quorum
      sensing system of the biofilm isolate Serratia plymuthica RVH1. Here we
      investigated the role of quorum sensing and of quorum-sensing-dependent
      production of an antimicrobial compound (AC) on biofilm formation by RVH1 and on
      the cocultivation of RVH1 and Escherichia coli in planktonic cultures or in
      biofilms. Biofilm formation of S. plymuthica was not affected by the knockout of
      splI or splR, the S. plymuthica homologs of the luxI or luxR quorum-sensing gene,
      respectively, or by the knockout of AC production. E. coli grew well in mixed
      broth culture with RVH1 until the latter reached 8.5 to 9.5 log CFU/ml, after
      which the E. coli colony counts steeply declined. In comparison, only a very
      small decline occurred in cocultures with the S. plymuthica AC-deficient and splI
      mutants. Complementation with exogenous N-hexanoyl-l-homoserine lactone rescued
      the wild-type phenotype of the splI mutant. The splR knockout mutant also induced
      a steep decline of E. coli, consistent with its proposed function as a repressor
      of quorum-sensing-regulated genes. The numbers of E. coli in 3-day-old mixed
      biofilms followed a similar pattern, being higher with S. plymuthica deficient in
      SplI or AC production than with wild-type S. plymuthica, the splR mutant, or the
      splI mutant in the presence of N-hexanoyl-l-homoserine lactone. Confocal laser
      scanning microscopic analysis of mixed biofilms established with strains
      producing different fluorescent proteins showed that E. coli microcolonies were
      less developed in the presence of RVH1 than in the presence of the AC-deficient
      mutant.

PMID- 16997990
TI  - Identification of pyruvate carboxylase genes in Pseudomonas aeruginosa PAO1 and
      development of a P. aeruginosa-based overexpression system for alpha4- and
      alpha4beta4-type pyruvate carboxylases.
AB  - Pyruvate carboxylase (PYC) is an ecologically, medically, and industrially
      important enzyme. It is widespread in all three domains of life, the archaea,
      bacteria, and eukarya. PYC catalyzes ATP-dependent carboxylation of pyruvate to
      oxaloacetate. Detailed structure-function studies of this enzyme have been
      hampered due to the unavailability of a facile recombinant overexpression system.
      Except for the alpha4 enzyme from a thermophilic Bacillus species, Escherichia
      coli has been unsuitable for overexpression of PYCs. We show that a Pseudomonas
      aeruginosa strain carrying the T7 polymerase gene can serve as a host for the
      overexpression of Mycobacterium smegmatis alpha4 PYC and Pseudomonas aeruginosa
      alpha4beta4 PYC under the control of the T7 promoter from a broad-host-range
      conjugative plasmid. Overexpression occurred both in aerobic (LB medium) and
      nitrate-respiring anaerobic (LB medium plus glucose and nitrate) cultures. The
      latter system presented a simpler option because it involved room temperature
      cultures in stationary screw-cap bottles. We also developed a P. aeruginosa
      Deltapyc strain that allowed the expression of recombinant PYCs in the absence of
      the native enzyme. Since P. aeruginosa can be transformed genetically and lysed
      for cell extract preparation rather easily, our system will facilitate site
      directed mutagenesis, kinetics, X-ray crystallographic, and nuclear magnetic
      resonance-based structure-function analysis of PYCs. During this work we also
      determined that, contrary to a previous report (C. K. Stover et al., Nature
      406:959-964, 2000), the open reading frame (ORF) PA1400 does not encode a PYC in
      P. aeruginosa. The alpha4beta4 PYC of this organism was encoded by the ORFs
      PA5436 and PA5435.

PMID- 16997991
TI  - Rapid chromatic detection of bacteria by use of a new biomimetic polymer sensor.
AB  - We present a new platform for visual and spectroscopic detection of bacteria. The
      detection scheme is based on the interaction of membrane-active compounds
      secreted by bacteria with agar-embedded nanoparticles comprising phospholipids
      and the chromatic polymer polydiacetylene (PDA). We demonstrate that PDA
      undergoes dramatic visible blue-to-red transformations together with an intense
      fluorescence emission that are induced by molecules released by multiplying
      bacteria. The chromatic transitions are easily identified by the naked eye and
      can also be recorded by conventional high-throughput screening instruments.
      Furthermore, the color and fluorescence changes generally occur in shorter times
      than the visual appearance of bacterial colonies on the agar. The chromatic
      technology is generic and simple, does not require identification a priori of
      specific bacterial recognition elements, and can be applied for detection of both
      gram-negative and gram-positive bacteria. We demonstrate applications of the new
      platform for reporting on bacterial contaminations in foods and for screening for
      bacterial antibiotic resistance.

PMID- 16997992
TI  - Mechanism of augmentation of organotin decomposition by ferripyochelin: formation
      of hydroxyl radical and organotin-pyochelin-iron ternary complex.
AB  - Pyochelin (PCH), a kind of siderophore secreted by Pseudomonas aeruginosa, was
      recently found to have triphenyltin (TPT)-decomposing capacity. In this work,
      significant augmentation of TPT decomposition by ferripyochelin (FePCH), the
      chelating compound of PCH with iron, was demonstrated in Tris-HCl buffer (pH
      8.0). The generation of hydroxyl radical (HO.) in the presence of FePCH was
      observed. Inhibition of HO. generation by adding catalase and HO. scavengers
      (methanol and dimethyl sulfoxide) decreased TPT decomposition, while an increase
      in HO. formation in the presence of H(2)O(2) enhanced its decomposition. Our
      findings indicated that HO. generated in the reaction system was responsible for
      the enhanced TPT decomposition by FePCH versus PCH. The existence of the TPT
      pyochelin-iron ternary complex was demonstrated by electron spray ionization-mass
      spectrometry, tandem mass spectrometry, and (1)H nuclear magnetic resonance. On
      the basis of the above results, HO. produced in the presence of FePCH was deduced
      to be in close proximity to TPT and has more opportunity to attack the Sn-C bond,
      which resulted in the enhanced organotin decomposition. The information obtained
      may have considerable environmental significance.

PMID- 16997993
TI  - Genetic characterization of the phenylacetyl-coenzyme A oxygenase from the
      aerobic phenylacetic acid degradation pathway of Escherichia coli.
AB  - We show here that the paaABCDE genes of the paa cluster responsible for
      phenylacetate degradation in Escherichia coli W encode a five-component oxygenase
      that hydroxylates phenylacetyl-coenzyme A (CoA), the first intermediate of the
      pathway. The primary structure of the subunits of bacterial phenylacetyl-CoA
      oxygenases revealed that these enzymes constitute the prototype of a new and
      distinct group of the large bacterial diiron multicomponent oxygenase family.

PMID- 16997995
TI  - Outbreak of avian influenza H7N3 on a turkey farm in the Netherlands.
AB  - This case report describes the course of an outbreak of avian influenza on a
      Dutch turkey farm. When clinical signs were observed their cause remained
      unclear. However, serum samples taken for the monitoring campaign launched during
      the epidemic of highly pathogenic avian influenza in 2003, showed that all the
      remaining turkeys were seropositive against an H7 strain of avian influenza
      virus, and the virus was subsequently isolated from stored carcases. The results
      of a reverse-transcriptase pcr showed that a H7N3 strain was involved, and it was
      characterised as of low pathogenicity. However, its intravenous pathogenicity
      index was 2.4, characterising it as of high pathogenicity, suggesting that a
      mixture of strains of low and high pathogenicity may have been present in the
      isolate. The outbreak remained limited to three farms.

PMID- 16997994
TI  - Global gene expression analysis of yeast cells during sake brewing.
AB  - During the brewing of Japanese sake, Saccharomyces cerevisiae cells produce a
      high concentration of ethanol compared with other ethanol fermentation methods.
      We analyzed the gene expression profiles of yeast cells during sake brewing using
      DNA microarray analysis. This analysis revealed some characteristics of yeast
      gene expression during sake brewing and provided a scaffold for a molecular level
      understanding of the sake brewing process.

PMID- 16997996
TI  - Malignant catarrhal fever in pigs and a genetic comparison of porcine and
      ruminant virus isolates in Finland.
AB  - An outbreak of the sheep-associated form of malignant catarrhal fever (MCF) in a
      Finnish sow herd was diagnosed by histopathology and confirmed by PCR. Several
      gilts and sows were suffering from high fever and anorexia and had aborted, and
      six of them had died. Typical signs of lymphoproliferation and vasculitis were
      observed histologically in several tissues, including the uterus. Ovine
      herpesvirus-2 (OvHV-2) was detected by PCR in two sows. Sequences of the OvHV-2
      tegument protein gene obtained from the sows and from three cases of sheep
      associated mcf in Finnish cattle were compared and found to be identical. These
      are the first confirmed cases of mcf in pigs in Finland.

PMID- 16997997
TI  - Pathological and immunohistochemical study of gastrointestinal lesions in
      dolphins stranded in the Canary Islands.
AB  - This paper describes the gross, histopathological and immunohistochemical
      characteristics of gastrointestinal lesions and regional lymph nodes of six
      common dolphins (Delphinus delphis), 11 striped dolphins (Stenella coeruleoalba)
      and six Atlantic spotted dolphins (Stenella frontalis) found stranded along the
      coasts of the Canary Islands. The most common lesion was chronic granulomatous
      gastritis of the glandular stomach, associated with the parasite Pholeter
      gastrophilus, and characterised by the parasites, their eggs, or parasite debris
      in the mucosa, submucosa or tunica muscularis, surrounded by numerous lysozyme
      positive macrophages and neutrophils, and more peripherally by abundant fibrous
      tissue containing variable numbers of immunoglobulin (Ig) G+ plasma cells, and
      small numbers of CD3+ T lymphocytes and IgM+ and IgA+ plasma cells. Anisakis
      simplex nematodes were found in two dolphins that were also parasitised by P
      gastrophilus and had parasitic granulomatous gastritis and multiple small chronic
      gastric ulcers. Lymphoplasmacytic enteritis was found in eight cases, three of
      them parasitised by Diphyllobothrium species; the lesion was characterised by
      moderate to severe infiltrations of CD3+ T lymphocytes and IgG+ plasma cells,
      with small numbers of IgM+ and IgA+ plasma cells in the lamina propria and
      submucosa, mainly of the small intestine. One dolphin had severe fibrinopurulent
      peritonitis, which may have been secondary to gastric perforation caused by the
      large mural granulomatous gastritis associated with P gastrophilus parasitism.

PMID- 16997998
TI  - Effects of long-term feeding of a diet supplemented with clinoptilolite to dairy
      cows on the incidence of ketosis, milk yield and liver function.
AB  - Fifty-two clinically healthy Holstein cows were randomly assigned to one of three
      groups according to their age and parity. The first group (A) consisted of 17
      cows that were fed a concentrate ration supplemented with 1.25 per cent
      clinoptilolite, the second group (B) consisted of 17 cows fed a ration
      supplemented with 2.5 per cent clinoptilolite, and the third group (C) consisted
      of 18 cows, which were fed the basal ration containing no clinoptilolite. The
      rations were fed from four weeks before the cows' expected parturition dates
      until the beginning of the next dry period. Blood samples were collected from
      each animal at the start of the experiment, on the day of calving and then
      monthly, and analysed for serum glucose, ketone bodies, liver enzymes, blood urea
      nitrogen (BUN) and total proteins. The milk yield of each cow was recorded
      monthly. The cows in group B had significantly fewer cases of clinical ketosis
      during the first month after calving and a higher total milk yield. Feeding the
      cows with clinoptilolite for a long period had no apparent adverse effects on
      their liver function, and did not significantly affect the concentrations of
      glucose, ketone bodies, BUN and total proteins in their serum.

PMID- 16997999
TI  - Identification of oxacillin-resistant staphylococci in dogs with end-stage
      otitis.

PMID- 16998000
TI  - Canine distemper virus antibodies in the Asian elephant (Elaphas maximus).

PMID- 16998001
TI  - Monitoring of the oestrous cycle in a captive Malayan tapir (Tapirus indicus).

PMID- 16998002
TI  - Giardia species and other intestinal parasites in dogs in north-east and central
      Italy.

PMID- 16998003
TI  - Resistance of Fasciola hepatica to triclabendazole and albendazole in sheep in
      Spain.

PMID- 16998005
TI  - Efficacy of vaccination against canine parvovirus.

PMID- 16998006
TI  - Reporting of clinical scrapie in the UK.

PMID- 16998007
TI  - Insights into the cholecystokinin 2 receptor binding site and processes of
      activation.
AB  - The cholecystokinin (CCK) 2 receptor (CCK2R) appears as a pharmacological target
      for the treatment of many major diseases. To complete the mapping of the CCK2R
      binding site and its activation processes, we have looked for the receptor
      residues that interact with Trp6, an essential residue for CCK binding and
      activity. In our molecular model of the CCK-occupied CCK2R, the indole group of
      Trp6 stacked with the phenyl ring of Phe120 (ECL1) and interacted with the
      imidazole group of His381(H7.39) and the phenyl ring of Tyr385(H7.43).
      Mutagenesis and pharmacological studies validated these interactions. It is
      noteworthy that the mutation of Phe120 to Trp conferred constitutive activity to
      the CCK2R. Molecular modeling and experimental works identified the residues
      involved in the activation cascade initiated by Trp6 and revealed that the
      constitutively active F120W mutation mimics the conformational changes induced by
      Trp6 resulting in: 1) the exposure of Glu151(E3.49) of the conserved E/DRY motif
      2) the formation of an amphiphatic pocket involving protonated Glu151(E3.49) and
      Leu330 (ICL3), and 3) the opening of the intracellular loops 2 and 3 and the
      release of Arg158 (ICL2). The R158A mutation was shown to affect inositol
      phosphate production, whereas the E151A and L330E mutations induced constitutive
      inositol phosphate production. Given that a constitutively active variant of the
      CCK2R has been identified in different cancers and the fact that the E151A mutant
      has been reported to induce tumors, these studies should help in the development
      of potent inverse agonists to inhibit the constitutive activation of the CCK2R.

PMID- 16998069
TI  - PDV1 and PDV2 mediate recruitment of the dynamin-related protein ARC5 to the
      plastid division site.
AB  - During plastid division, the dynamin-related protein ACCUMULATION AND REPLICATION
      OF CHLOROPLASTS5 (ARC5) is recruited from the cytosol to the surface of the outer
      chloroplast envelope membrane. In Arabidopsis thaliana arc5 mutants, chloroplasts
      arrest during division site constriction. Analysis of mutants similar to arc5
      along with map-based cloning identified PLASTID DIVISION1 (PDV1), an integral
      outer envelope membrane protein, and its homolog PDV2 as components of the
      plastid division machinery. Similar to ARC5, PDV1 localized to a discontinuous
      ring at the division site in wild-type plants. The midplastid PDV1 ring formed in
      arc5 mutants and the ARC5 ring formed in pdv1 and pdv2 mutants, but not in pdv1
      pdv2. Stromal FtsZ ring assembly occurred in pdv1, pdv2, and pdv1 pdv2, as it
      does in arc5. Topological analysis showed that the large N-terminal region of
      PDV1 upstream of the transmembrane helix bearing a putative coiled-coil domain is
      exposed to the cytosol. Mutation of the conserved PDV1 C-terminal Gly residue did
      not block PDV1 insertion into the outer envelope membrane but did abolish its
      localization to the division site. Our results indicate that plastid division
      involves the stepwise localization of FtsZ, PDV1, and ARC5 at the division site
      and that PDV1 and PDV2 together mediate the recruitment of ARC5 to the midplastid
      constriction at a late stage of division.

PMID- 16998071
TI  - Crystal structure of Vigna radiata cytokinin-specific binding protein in complex
      with zeatin.
AB  - The cytosolic fraction of Vigna radiata contains a 17-kD protein that binds plant
      hormones from the cytokinin group, such as zeatin. Using recombinant protein and
      isothermal titration calorimetry as well as fluorescence measurements coupled
      with ligand displacement, we have reexamined the K(d) values and show them to
      range from approximately 10(-6) M (for 4PU30) to 10(-4) M (for zeatin) for 1:1
      stoichiometry complexes. In addition, we have crystallized this cytokinin
      specific binding protein (Vr CSBP) in complex with zeatin and refined the
      structure to 1.2 A resolution. Structurally, Vr CSBP is similar to plant
      pathogenesis-related class 10 (PR-10) proteins, despite low sequence identity
      (<20%). This unusual fold conservation reinforces the notion that classic PR-10
      proteins have evolved to bind small-molecule ligands. The fold consists of an
      antiparallel beta-sheet wrapped around a C-terminal alpha-helix, with two short
      alpha-helices closing a cavity formed within the protein core. In each of the
      four independent CSBP molecules, there is a zeatin ligand located deep in the
      cavity with conserved conformation and protein-ligand interactions. In three
      cases, an additional zeatin molecule is found in variable orientation but with
      excellent definition in electron density, which plugs the entrance to the binding
      pocket, sealing the inner molecule from contact with bulk solvent.

PMID- 16998070
TI  - An Arabidopsis glutathione peroxidase functions as both a redox transducer and a
      scavenger in abscisic acid and drought stress responses.
AB  - We isolated two T-DNA insertion mutants of Arabidopsis thaliana GLUTATHIONE
      PEROXIDASE3 (ATGPX3) that exhibited a higher rate of water loss under drought
      stress, higher sensitivity to H(2)O(2) treatment during seed germination and
      seedling development, and enhanced production of H(2)O(2) in guard cells. By
      contrast, lines engineered to overexpress ATGPX3 were less sensitive to drought
      stress than the wild type and displayed less transpirational water loss, which
      resulted in higher leaf surface temperature. The atgpx3 mutation also disrupted
      abscisic acid (ABA) activation of calcium channels and the expression of ABA- and
      stress-responsive genes. ATGPX3 physically interacted with the 2C-type protein
      phosphatase ABA INSENSITIVE2 (ABI2) and, to a lesser extent, with ABI1. In
      addition, the redox states of both ATGPX3 and ABI2 were found to be regulated by
      H(2)O(2). The phosphatase activity of ABI2, measured in vitro, was reduced
      approximately fivefold by the addition of oxidized ATGPX3. The reduced form of
      ABI2 was converted to the oxidized form by the addition of oxidized ATGPX3 in
      vitro, which might mediate ABA and oxidative signaling. These results suggest
      that ATGPX3 might play dual and distinctive roles in H(2)O(2) homeostasis, acting
      as a general scavenger and specifically relaying the H(2)O(2) signal as an
      oxidative signal transducer in ABA and drought stress signaling.

PMID- 16998073
TI  - Candida albicans transcription factor Ace2 regulates metabolism and is required
      for filamentation in hypoxic conditions.
AB  - Ace2 transcription factor family genes are found in many fungal genomes and are
      required for regulation of expression of genes involved in cell separation. We
      used transcriptional profiling to identify the targets of Ace2 in Candida
      albicans, and we show that these include several cell wall components, such as
      glucanases and glycosylphosphatidylinositol-anchored proteins. Expression is
      downregulated in ace2 deletion mutants in both yeast and hyphal cells. In
      addition, deleting ace2 results in dramatic changes in expression of metabolic
      pathways. Expression of glycolytic enzymes is reduced, while expression of
      respiratory genes (including those involved in the tricarboxylic acid cycle,
      oxidative phosphorylation, and ATP synthesis) is increased. Similar changes occur
      in both yeast and hyphal cells. In contrast, genes required for acetyl-coenzyme A
      and lipid metabolism are upregulated in an ace2 deletion mutant grown
      predominantly as yeast cells but are downregulated in hyphae. These results
      suggest that in wild-type strains, Ace2 acts to increase glycolysis and reduce
      respiration. This is supported by the observation that deleting ace2 results in
      increased resistance to antimycin A, a drug that inhibits respiration. We also
      show that Ace2 is required for filamentation in response to low oxygen
      concentrations (hypoxia). We suggest that filamentation is induced in wild-type
      cells by reducing respiration (using low oxygen or respiratory drugs) and that
      mutants with increased respiratory activity fail to undergo filamentation under
      these conditions.

PMID- 16998074
TI  - Novel mitogen-activated protein kinase MpkC of Aspergillus fumigatus is required
      for utilization of polyalcohol sugars.
AB  - The genome of Aspergillus fumigatus has four genes that encode mitogen-activated
      protein kinases (MAPKs), sakA/hogA, mpkA, mpkB, and mpkC. The functions of the
      MpkB and MpkC MAPKs are unknown for A. fumigatus and the closely related and
      genetically amenable species Aspergillus nidulans. mpkC deletion mutants of A.
      fumigatus were made and their phenotypes characterized. The mpkC deletion mutants
      were viable and had normal conidial germination and hyphal growth on minimal or
      complete media. This is in contrast to deletion mutants with deletions in the
      closely related MAPK gene sakA/hogA that we previously reported had a nitrogen
      source-dependent germination phenotype. Similarly, the growth of the mpkC
      deletion mutants was wild type on high-osmolarity medium. Consistent with these
      two MAP kinase genes regulating different cellular responses, we determined that
      the mpkC deletion mutants were unable to grow on minimal medium with sorbitol or
      mannitol as the sole carbon source. This result implicates MpkC signaling in
      carbon source utilization. Changes in mRNA levels for sakA and mpkC were measured
      in response to hypertonic stress, oxidative stress, and a shift from glucose to
      sorbitol to determine if there was overlap in the SakA and MpkC signaling
      pathways. These studies demonstrated that SakA- and MpkC-dependent patterns of
      change in mRNA levels are distinct and have minimal overlap in response to these
      environmental stresses.

PMID- 16998072
TI  - Analysis of Euglena gracilis plastid-targeted proteins reveals different classes
      of transit sequences.
AB  - The plastid of Euglena gracilis was acquired secondarily through an endosymbiotic
      event with a eukaryotic green alga, and as a result, it is surrounded by a third
      membrane. This membrane complexity raises the question of how the plastid
      proteins are targeted to and imported into the organelle. To further explore
      plastid protein targeting in Euglena, we screened a total of 9,461 expressed
      sequence tag (EST) clusters (derived from 19,013 individual ESTs) for full-length
      proteins that are plastid localized to characterize their targeting sequences and
      to infer potential modes of translocation. Of the 117 proteins identified as
      being potentially plastid localized whose N-terminal targeting sequences could be
      inferred, 83 were unique and could be classified into two major groups. Class I
      proteins have tripartite targeting sequences, comprising (in order) an N-terminal
      signal sequence, a plastid transit peptide domain, and a predicted stop-transfer
      sequence. Within this class of proteins are the lumen-targeted proteins (class
      IB), which have an additional hydrophobic domain similar to a signal sequence and
      required for further targeting across the thylakoid membrane. Class II proteins
      lack the putative stop-transfer sequence and possess only a signal sequence at
      the N terminus, followed by what, in amino acid composition, resembles a plastid
      transit peptide. Unexpectedly, a few unrelated plastid-targeted proteins exhibit
      highly similar transit sequences, implying either a recent swapping of these
      domains or a conserved function. This work represents the most comprehensive
      description to date of transit peptides in Euglena and hints at the complex
      routes of plastid targeting that must exist in this organism.

PMID- 16998075
TI  - The multifunctional beta-oxidation enzyme is required for full symptom
      development by the biotrophic maize pathogen Ustilago maydis.
AB  - The transition from yeast-like to filamentous growth in the biotrophic fungal
      phytopathogen Ustilago maydis is a crucial event for pathogenesis. Previously, we
      showed that fatty acids induce filamentation in U. maydis and that the resulting
      hyphal cells resemble the infectious filaments observed in planta. To explore the
      potential metabolic role of lipids in the morphological transition and in
      pathogenic development in host tissue, we deleted the mfe2 gene encoding the
      multifunctional enzyme that catalyzes the second and third reactions in beta
      oxidation of fatty acids in peroxisomes. The growth of the strains defective in
      mfe2 was attenuated on long-chain fatty acids and abolished on very-long-chain
      fatty acids. The mfe2 gene was not generally required for the production of
      filaments during mating in vitro, but loss of the gene blocked extensive
      proliferation of fungal filaments in planta. Consistent with this observation,
      mfe2 mutants exhibited significantly reduced virulence in that only 27% of
      infected seedlings produced tumors compared to 88% tumor production upon
      infection by wild-type strains. Similarly, a defect in virulence was observed in
      developing ears upon infection of mature maize plants. Specifically, the absence
      of the mfe2 gene delayed the development of teliospores within mature tumor
      tissue. Overall, these results indicate that the ability to utilize host lipids
      contributes to the pathogenic development of U. maydis.

PMID- 16998076
TI  - Tcc1p, a novel protein containing the tetratricopeptide repeat motif, interacts
      with Tup1p to regulate morphological transition and virulence in Candida
      albicans.
AB  - The transcriptional factor CaTup1p represses many genes involved in intracellular
      processes, including the yeast-hypha transition, in the human fungal pathogen
      Candida albicans. Using tandem affinity purification technology, we identified a
      novel protein that interacts with CaTup1p, named Tcc1p (Tup1p complex component).
      Tcc1p is a C. albicans-specific protein with a 736-amino-acid polypeptide with
      four tetratricopeptide repeat (TPR) motifs in the N-terminal portion. Tcc1p
      formed a protein complex with CaTup1p via the TPR domain of Tcc1p, independently
      of CaSsn6p-CaTup1p The tcc1Delta disruptant showed filamentous growth under
      conditions inducing the yeast form, as is true of the Catup1Delta mutant.
      Consistent with this result, the common set of hypha-specific genes was
      negatively regulated by both TCC1 and CaTUP1. These observations will provide new
      insights into CaTup1p-dependent transcriptional gene regulation in C. albicans.

PMID- 16998077
TI  - Injury in childhood: a vexingly simple problem.

PMID- 16998078
TI  - Trends in rates of death from unintentional injury among Canadian children in
      urban areas: influence of socioeconomic status.

PMID- 16998079
TI  - Home safety measures and the risk of unintentional injury among young children: a
      multicentre case-control study.
AB  - BACKGROUND: Young children may sustain injuries when exposed to certain hazards
      in the home. To better understand the relation between several childproofing
      strategies and the risk of injuries to children in the home, we undertook a
      multicentre case-control study in which we compared hazards in the homes of
      children with and without injuries. METHODS: We conducted this case-control study
      using records from 5 pediatric hospital emergency departments for the 2-year
      period 1995-1996. The 351 case subjects were children aged 7 years and less who
      presented with injuries from falls, burns or scalds, ingestions or choking. The
      matched control subjects were children who presented during the same period with
      acute non-injury-related conditions. A home visitor, blinded to case-control
      status, assessed 19 injury hazards at the children's homes. RESULTS: Hazards
      found in the homes included baby walkers (21% of homes with infants), no
      functioning smoke alarm (17% of homes) and no fire extinguisher (51% of homes).
      Cases did not differ from controls in the mean proportion of home hazards. After
      controlling for siblings, maternal education and employment, we found that cases
      differed from controls for 5 hazards: the presence of a baby walker (odds ratio
      [OR] 9.0, 95% confidence interval [CI] 1.1-71.0), the presence of choking hazards
      within a child's reach (OR 2.0, 95% CI 1.0-3.7), no child-resistant lids in
      bathroom (OR 1.6, 95% CI 1.0-2.5), no smoke alarm (OR 3.2, 95% CI 1.4-7.7) and no
      functioning smoke alarm (OR 1.7, 95% CI 1.0-2.8). INTERPRETATION: Homes of
      children with injuries differed from those of children without injuries in the
      proportions of specific hazards for falls, choking, poisoning and burns, with a
      striking difference noted for the presence of a baby walker. In addition to
      counselling parents about specific hazards, clinicians should consider that the
      presence of some hazards may indicate an increased risk for home injuries beyond
      those directly related to the hazard found. Families with any home hazard may be
      candidates for interventions to childproof against other types of home hazards.

PMID- 16998081
TI  - Canada gets a marginal grade on childhood injury.

PMID- 16998082
TI  - Changes of Achilles midportion tendon microcirculation after repetitive
      simultaneous cryotherapy and compression using a Cryo/Cuff.
AB  - BACKGROUND: Cryotherapy and compression have been shown to decrease pain and
      improve function. The dosage and timing of these options remain unclear. PURPOSE:
      To examine the effects of a standardized compression and cryotherapy device
      (Cryo/Cuff) on midportion Achilles tendon microcirculation during intermittent
      administration. STUDY DESIGN: Descriptive laboratory study. METHODS: Twenty-six
      subjects were included (13 men and 13 women; age, 32.3 +/- 12 years; body mass
      index, 25.4 +/- 5 kg/m(2)). Each underwent three 10-minute applications of the
      device, followed by a 10-minute recovery period. A continuous real-time
      assessment of parameters of Achilles tendon midportion microcirculation was
      performed with a laser Doppler spectrophotometry system. RESULTS: Superficial
      tendon oxygen saturation dropped significantly from 35.9 +/- 21 arbitrary units
      (AU) to 13.5 +/- 15, 15.9 +/- 16, and 11.1 +/- 11 AU (P = .0001) during each
      period of cryo-compression, respectively. There was significant increase during
      the recovery period (55.4 +/- 29, 65.2 +/- 26, and 65.7 +/- 27 AU; P = .003), up
      to +83% of the baseline level. At 8-mm tendon depth, cryo-compression preserved
      local oxygen with -4% (P = .001) of the baseline level and small but significant
      increased oxygen saturation of up to +13% (P = .0001). Relative postcapillary
      venous tendon filling pressures were favorably reduced both superficially (57% +/
      34%, 67% +/- 27%, and 64% +/- 38%, respectively; P = .0004) and deep (76% +/-
      13%, 79% +/- 11%, and 78% +/- 18%, respectively; P = .0002). Superficial
      capillary blood flow was reduced from 48.4 +/- 48 to 5 +/- 7, 4 +/- 5, and 3 +/-
      4 AU at each period, respectively (-94%, P = .0003), with increased flow during
      recovery periods of up to 58 +/- 64, 58 +/- 79, and 47 +/- 71 AU, respectively
      (+20%, P = .265). Deep flow was reduced from 197 +/- 147 to 66.7 +/- 64, 55 +/-
      46, and 43 +/- 39 AU, respectively (-78%, P = .0002) without increase during
      recovery periods. CONCLUSION: Cryo/Cuff exerts beneficial effects on the
      microcirculatory level of the midportion Achilles tendon with decreased capillary
      blood flow, preserved deep tendon oxygen saturation, and facilitated venous
      capillary outflow.

PMID- 16998083
TI  - Radiographic measures of knee alignment in patients with varus gonarthrosis:
      effect of weightbearing status and associations with dynamic joint load.
AB  - BACKGROUND: Radiographic measures of lower limb malalignment are used to indicate
      abnormal loading of the knee and to plan corrective procedures. HYPOTHESES:
      Weightbearing status during hip-to-ankle radiographs will significantly affect
      malalignment measures; malalignment in single-limb standing will be most highly
      correlated to the external knee adduction moment during gait, a proposed dynamic
      measure of functional knee joint load. STUDY DESIGN: Controlled laboratory study.
      METHODS: Mechanical axis angle was measured in 40 patients with varus
      gonarthrosis from hip-to-ankle radiographs taken with patients in single-limb
      standing, double-limb standing, and supine positions. Kinematic and kinetic data
      were collected during walking and used to calculate the peak adduction moment
      about the knee. RESULTS: Repeated-measures analysis of variance and Scheffe post
      hoc tests indicated that mechanical axis angle measured on single-limb standing
      radiographs (-8.7 degrees +/- 4.0 degrees) was significantly greater than on
      double-limb standing radiographs (-7.1 degrees +/- 3.8 degrees), which was
      significantly greater than on supine radiographs (-5.5 degrees +/- 2.8 degrees).
      The peak knee adduction moment (2.8 +/- 0.8 percentage body weight x height) was
      only moderately correlated with mechanical axis angle on single-limb standing (r
      = -0.46), double-limb standing (r = -0.45), and supine (r = -0.43) radiographs.
      CONCLUSION: Patient position significantly affects frontal plane knee alignment.
      However, the peak knee adduction moment is only moderately correlated to
      mechanical axis angle, regardless of weightbearing status. CLINICAL RELEVANCE:
      These findings are inconsistent with the hypothesis that mechanical axis angle
      measured in single-limb standing is more representative of dynamic joint load and
      further highlight the differences between static and dynamic measures. Results
      also underscore the importance of reporting patient position during radiographs
      and keeping positions consistent when evaluating patients over time.

PMID- 16998084
TI  - Improved resistance to controlled deterioration in transgenic seeds.
AB  - We show that seed-specific overexpression of the sunflower (Helianthus annuus)
      HaHSFA9 heat stress transcription factor (HSF) in tobacco (Nicotiana tabacum)
      enhances the accumulation of heat shock proteins (HSPs). Among these proteins
      were HSP101 and a subset of the small HSPs, including proteins that accumulate
      only during embryogenesis in the absence of thermal stress. Levels of late
      embryogenesis abundant proteins or seed oligosaccharides, however, were not
      affected. In the transgenic seeds, a high basal thermotolerance persisted during
      the early hours of imbibition. Transgenic seeds also showed significantly
      improved resistance to controlled deterioration in a stable and transgene
      dependent manner. Furthermore, overexpression of HaHSFA9 did not have detrimental
      effects on plant growth or development, including seed morphology and total seed
      yield. Our results agree with previous work tentatively associating HSP gene
      expression with phenotypes important for seed longevity. These findings might
      have implications for improving seed longevity in economically important crops.

PMID- 16998085
TI  - Regulation of the high-affinity NO3- uptake system by NRT1.1-mediated NO3- demand
      signaling in Arabidopsis.
AB  - The NRT2.1 gene of Arabidopsis thaliana encodes a major component of the root
      high-affinity NO(3)(-) transport system (HATS) that plays a crucial role in
      NO(3)(-) uptake by the plant. Although NRT2.1 was known to be induced by NO(3)(-)
      and feedback repressed by reduced nitrogen (N) metabolites, NRT2.1 is
      surprisingly up-regulated when NO(3)(-) concentration decreases to a low level
      (<0.5 mm) in media containing a high concentration of NH(4)(+) or Gln (>or=1 mm).
      The NRT3.1 gene, encoding another key component of the HATS, displays the same
      response pattern. This revealed that both NRT2.1 and NRT3.1 are coordinately down
      regulated by high external NO(3)(-) availability through a mechanism independent
      from that involving N metabolites. We show here that repression of both genes by
      high NO(3)(-) is specifically mediated by the NRT1.1 NO(3)(-) transporter. This
      mechanism warrants that either NRT1.1 or NRT2.1 is active in taking up NO(3)(-)
      in the presence of a reduced N source. Under low NO(3)(-)/high NH(4)(+)
      provision, NRT1.1-mediated repression of NRT2.1/NRT3.1 is relieved, which allows
      reactivation of the HATS. Analysis of atnrt2.1 mutants showed that this
      constitutes a crucial adaptive response against NH(4)(+) toxicity because NO(3)(
      ) taken up by the HATS in this situation prevents the detrimental effects of pure
      NH(4)(+) nutrition. It is thus hypothesized that NRT1.1-mediated regulation of
      NRT2.1/NRT3.1 is a mechanism aiming to satisfy a specific NO(3)(-) demand of the
      plant in relation to the various specific roles that NO(3)(-) plays, in addition
      to being a N source. A new model is proposed for regulation of the HATS,
      involving both feedback repression by N metabolites and NRT1.1-mediated
      repression by high NO(3)(-).

PMID- 16998086
TI  - Exogenous free ubiquitin enhances lily pollen tube adhesion to an in vitro stylar
      matrix and may facilitate endocytosis of SCA.
AB  - Pollen tube adhesion and guidance on extracellular matrices within the pistil are
      essential processes that convey the pollen tube cell and the sperm cells to the
      ovule. In this study, we purified an additional molecule from the pistil that
      enhances pollen tube adhesion when combined with the SCA (stigma/stylar cysteine
      rich adhesin)/pectin matrix in our in vitro assay. The enhancer of adhesion was
      identified as free ubiquitin (Ub). This was confirmed by use of bovine Ub as a
      substitute for lily (Lilium longiflorum Thunb.) stigma Ub. To study the
      interaction of SCA and Ub with the lily pollen tube, we labeled both proteins
      with biotin. We observed uptake of biotin-labeled SCA and Ub into the pollen tube
      cells in vitro using confocal microscopy. For SCA, a strong signal occurred first
      at the tip of the pollen tube, suggestive of an endocytosis event, and then
      progressively throughout the tube cytoplasm. SCA was also localized inside the in
      vivo pollen tube using immunogold electron microscopy and found to be present in
      endosomes, multivesicular bodies, and vacuoles, all known to be endocytic
      compartments. It was also confirmed that SCA is endocytosed in the in vitro
      adhesion assay. Internalization of SCA was increased in pollen tubes treated with
      exogenous Ub compared to those without Ub, suggesting that Ub may facilitate SCA
      endocytosis. These results show that Ub can act as an enhancer of pollen tube
      adhesion in vitro and that it is taken up into the pollen tube as is SCA. The Ub
      machinery may play a role in pollen tube adhesion and guidance in lily.

PMID- 16998087
TI  - The Arabidopsis unannotated secreted peptide database, a resource for plant
      peptidomics.
AB  - In the era of genomics, if a gene is not annotated, it is not investigated. Due
      to their small size, genes encoding peptides are often missed in genome
      annotations. Secreted peptides are important regulators of plant growth,
      development, and physiology. Identification of additional peptide signals by
      sequence homology searches has had limited success due to sequence heterogeneity.
      A bioinformatics approach was taken to find unannotated Arabidopsis (Arabidopsis
      thaliana) peptides. Arabidopsis chromosome sequences were searched for all open
      reading frames (ORFs) encoding peptides and small proteins between 25 and 250
      amino acids in length. The translated ORFs were then sequentially queried for the
      presence of an amino-terminal cleavable signal peptide, the absence of
      transmembrane domains, and the absence of endoplasmic reticulum lumenal retention
      sequences. Next, the ORFs were filtered against the The Arabidopsis Information
      Resource 6.0 annotated Arabidopsis genes to remove those ORFs overlapping known
      genes. The remaining 33,809 ORFs were placed in a relational database to which
      additional annotation data were deposited. Genome-wide tiling array data were
      compared with the coordinates of the ORFs, supporting the possibility that many
      of the ORFs may be expressed. In addition, clustering and sequence similarity
      analyses revealed that many of the putative peptides are in gene families and/or
      appear to be present in the rice (Oryza sativa) genome. A subset of the ORFs was
      evaluated by reverse transcription-PCR and, for one-fifth of those, expression
      was detected. These results support the idea that the number and diversity of
      plant peptides is broader than currently assumed. The peptides identified and
      their annotation data may be viewed or downloaded through a searchable Web
      interface at peptidome.missouri.edu.

PMID- 16998089
TI  - An investigation of boron toxicity in barley using metabolomics.
AB  - Boron (B) is an essential micronutrient that affects plant growth at either
      deficient or toxic concentrations in soil. The aim of this work was to
      investigate the adaptation of barley (Hordeum vulgare) plants to toxic B levels
      and to increase our understanding of B toxicity tolerance mechanisms. We used a
      metabolomics approach to compare metabolite profiles in root and leaf tissues of
      an intolerant, commercial cultivar (cv Clipper) and a B-tolerant Algerian
      landrace (cv Sahara). After exposure to elevated B (200 and 1,000 microM), the
      number and amplitude of metabolite changes in roots was greater in Clipper than
      in Sahara. In contrast, leaf metabolites of both cultivars only responded
      following 1,000 microM treatment, at which B toxicity symptoms (necrosis) were
      visible. In addition, metabolite levels were dramatically altered in the tips of
      leaves of the sensitive cultivar Clipper after growth in 1,000 microM B compared
      to those of Sahara. This correlates with a gradual accumulation of B from leaf
      base to tip in B-intolerant cultivars. Overall, there were always greater
      differences between tissue types (roots and leaves) than between the two
      cultivars. This work has provided insights into metabolic differences of two
      genetically distinct barley cultivars and information about how they respond
      metabolically to increasing B levels.

PMID- 16998088
TI  - The Arabidopsis tetratricopeptide repeat-containing protein TTL1 is required for
      osmotic stress responses and abscisic acid sensitivity.
AB  - Mutations in the Arabidopsis (Arabidopsis thaliana) TETRATRICOPEPTIDE-REPEAT
      THIOREDOXIN-LIKE 1 (TTL1) cause reduced tolerance to NaCl and osmotic stress that
      is characterized by reduced root elongation, disorganization of the root
      meristem, and impaired osmotic responses during germination and seedling
      development. Expression analyses of genes involved in abscisic acid (ABA)
      biosynthesis and catabolism suggest that TTL1 is not involved in the regulation
      of ABA levels but is required for ABA-regulated responses. TTL1 regulates the
      transcript levels of several dehydration-responsive genes, such as the
      transcription factor DREB2A, and genes encoding dehydration response proteins,
      such as ERD1 (early response to dehydration 1), ERD3, and COR15a. The TTL1 gene
      encodes a novel plant protein with tetratricopeptide repeats and a region with
      homology to thioredoxin proteins. Based on homology searches, there are four TTL
      members in the Arabidopsis genome with similar intron-exon structure and
      conserved amino acid domains. Proteins containing tetratricopeptide repeat motifs
      act as scaffold-forming multiprotein complexes and are emerging as essential
      elements for plant hormonal responses (such as gibberellin responses and ethylene
      biosynthesis). In this report, we identify TTL1 as a positive regulator of ABA
      signaling during germination and seedling development under stress.

PMID- 16998090
TI  - Functional classification, genomic organization, putatively cis-acting regulatory
      elements, and relationship to quantitative trait loci, of sorghum genes with
      rhizome-enriched expression.
AB  - Rhizomes are organs of fundamental importance to plant competitiveness and
      invasiveness. We have identified genes expressed at substantially higher levels
      in rhizomes than other plant parts, and explored their functional categorization,
      genomic organization, regulatory motifs, and association with quantitative trait
      loci (QTLs) conferring rhizomatousness. The finding that genes with rhizome
      enriched expression are distributed across a wide range of functional categories
      suggests some degree of specialization of individual members of many gene
      families in rhizomatous plants. A disproportionate share of genes with rhizome
      enriched expression was implicated in secondary and hormone metabolism, and
      abiotic stimuli and development. A high frequency of unknown-function genes
      reflects our still limited knowledge of this plant organ. A putative
      oligosaccharyl transferase showed the highest degree of rhizome-specific
      expression, with several transcriptional or regulatory protein complex factors
      also showing high (but lesser) degrees of specificity. Inferred by the upstream
      sequences of their putative rice (Oryza sativa) homologs, sorghum (Sorghum
      bicolor) genes that were relatively highly expressed in rhizome tip tissues were
      enriched for cis-element motifs, including the pyrimidine box, TATCCA box, and
      CAREs box, implicating the gibberellins in regulation of many rhizome-specific
      genes. From cDNA clones showing rhizome-enriched expression, expressed sequence
      tags forming 455 contigs were plotted on the rice genome and aligned to QTL
      likelihood intervals for ratooning and rhizomatous traits in rice and sorghum.
      Highly expressed rhizome genes were somewhat enriched in QTL likelihood intervals
      for rhizomatousness or ratooning, with specific candidates including some of the
      most rhizome-specific genes. Some rhizomatousness and ratooning QTLs were shown
      to be potentially related to one another as a result of ancient duplication,
      suggesting long-term functional conservation of the underlying genes. Insight
      into genes and pathways that influence rhizome growth set the stage for genetic
      and/or exogenous manipulation of rhizomatousness, and for further dissection of
      the molecular evolution of rhizomatousness.

PMID- 16998091
TI  - Large expression differences in genes for iron and zinc homeostasis, stress
      response, and lignin biosynthesis distinguish roots of Arabidopsis thaliana and
      the related metal hyperaccumulator Thlaspi caerulescens.
AB  - The micronutrient zinc has an essential role in physiological and metabolic
      processes in plants as a cofactor or structural element in 300 catalytic and
      noncatalytic proteins, but it is very toxic when available in elevated amounts.
      Plants tightly regulate their internal zinc concentrations in a process called
      zinc homeostasis. The exceptional zinc hyperaccumulator species Thlaspi
      caerulescens can accumulate up to 3% of zinc, but also high amounts of nickel and
      cadmium, without any sign of toxicity. This should have drastic effects on the
      zinc homeostasis mechanism. We examined in detail the transcription profiles of
      roots of Arabidopsis thaliana and T. caerulescens plants grown under deficient,
      sufficient, and excess supply of zinc. A total of 608 zinc-responsive genes with
      at least a 3-fold difference in expression level were detected in A. thaliana and
      352 in T. caerulescens in response to changes in zinc supply. Only 14% of these
      genes were also zinc responsive in A. thaliana. When comparing A. thaliana with
      T. caerulescens at each zinc exposure, more than 2,200 genes were significantly
      differentially expressed (>or=5-fold and false discovery rate < 0.05). While a
      large fraction of these genes are of yet unknown function, many genes with a
      different expression between A. thaliana and T. caerulescens appear to function
      in metal homeostasis, in abiotic stress response, and in lignin biosynthesis. The
      high expression of lignin biosynthesis genes corresponds to the deposition of
      lignin in the endodermis, of which there are two layers in T. caerulescens roots
      and only one in A. thaliana.

PMID- 16998092
TI  - Maternal complications and procedures in pregnancy and at birth and wheezing
      phenotypes in children.
AB  - RATIONALE: There is increasing interest in the potential influence of fetal and
      early life conditions on childhood wheezing. OBJECTIVES: To investigate the
      associations between maternal complications and procedures in pregnancy and at
      birth and the risk of various wheezing phenotypes in young children. METHODS: We
      studied 15,609 children, aged 6-7 yr, enrolled in a population-based study.
      Standardized questionnaires were completed by the children's mothers. RESULTS: Of
      the children, 9.5% (1,478) had transient early wheezing, 5.4% (884) had
      persistent wheezing, and 6.1% (948) had late-onset wheezing. Maternal
      hypertension or preeclampsia was associated with an increased risk of all three
      wheezing phenotypes (for transient early wheezing: odds ratio [OR], 1.40; 95%
      confidence interval [95% CI], 1.08-1.82; for persistent wheezing: OR, 1.59; 95%
      CI, 1.15-2.19; and for late-onset wheezing: OR, 1.47; 95% CI, 1.06-2.01). Use of
      antibiotics for urinary tract infections was associated with transient early
      wheezing (OR, 1.52; 95% CI, 1.16-2.00), whereas antibiotic administration at
      delivery was associated with both transient early wheezing (OR, 1.21; 95% CI,
      1.01-1.46) and persistent wheezing (OR, 1.39; 95% CI, 1.10-1.75). Children who
      had a mother with diabetes were also more likely to have persistent wheezing (OR,
      1.72; 95% CI, 0.99-3.00). Neither amniocentesis/chorionic villus sampling, nor
      weight gain in pregnancy, nor cesarean section was associated with the subsequent
      development of wheezing. Maternal asthma or atopy was not an effect modifier of
      the associations found. CONCLUSIONS: Some maternal complications during pregnancy
      and at delivery may increase the risk of developing different phenotypes of
      wheezing in childhood.

PMID- 16998093
TI  - Fluid shift by lower body positive pressure increases pharyngeal resistance in
      healthy subjects.
AB  - INTRODUCTION: Fluid displacement into nuchal and peripharyngeal soft tissues
      while recumbent may contribute to narrowing and increased airflow resistance of
      the pharynx (Rph), and predispose to pharyngeal collapse in patients at risk for
      obstructive sleep apnea. OBJECTIVES: To determine whether displacement of fluid
      from the lower body to the neck will increase both neck circumference and Rph in
      healthy subjects. METHODS: In 11 healthy, nonobese subjects, studied while awake
      and supine, leg fluid volume, neck circumference, and Rph were measured at
      baseline. Subjects were then randomized to a control period or to application of
      lower body positive pressure (LBPP) of 40 mm Hg via antishock trousers to
      displace fluid from the legs, after which they crossed over to the other arm.
      Baseline measurements were repeated at 1 and 5 min during the control and LBPP
      periods. RESULTS: Compared with the control period, application of LBPP caused a
      significant reduction in leg fluid volume (p < 0.001) and a significant increase
      in neck circumference (p = 0.004). Rph remained stable during the control period,
      but increased significantly from baseline after 1 and 5 min of LBPP (from 0.43 +/
      0.10 to 0.60 +/- 0.11 cm H(2)O/L/s, p = 0.034, and to 0.87 +/- 0.19 cm
      H(2)O/L/s, p < 0.001, compared with baseline, respectively). CONCLUSIONS: Fluid
      displacement from the legs by LBPP increases neck circumference and Rph in
      healthy subjects. These findings suggest the hypothesis that fluid displacement
      to the upper body during recumbency may predispose to pharyngeal obstruction
      during sleep, especially in fluid overload states, such as heart and renal
      failure.

PMID- 16998094
TI  - Clinical trial of low-dose theophylline and montelukast in patients with poorly
      controlled asthma.
AB  - BACKGROUND: Asthma treatment guidelines recommend addition of controller
      medications for patients with poorly controlled asthma. We compared the
      effectiveness of once-daily oral controller therapy with either an
      antileukotriene receptor antagonist (montelukast) or low-dose theophylline added
      to existing medications in patients with poorly controlled asthma. METHODS: We
      conducted a randomized, double-masked, placebo-controlled trial in 489
      participants with poorly controlled asthma randomly assigned to placebo,
      theophylline (300 mg/d), or montelukast (10 mg/d). Participants were monitored
      for 24 wk to measure the rate of episodes of poor asthma control (EPACs) defined
      by decreased peak flow, increased beta-agonist use, increased oral corticosteroid
      use, or unscheduled health care visits. OBSERVATIONS: There was no significant
      difference in EPAC rates (events/person/yr) compared with placebo: low-dose
      theophylline, 4.9 (95% confidence interval [CI], 3.6-6.7; not significant);
      montelukast, 4.0 (95% CI, 3.0-5.4; not significant); and placebo, 4.9 (95% CI,
      3.8-6.4). Both montelukast and theophylline caused small improvements in
      prebronchodilator FEV(1) of borderline significance. Nausea was more common with
      theophylline only during the first 4 wk of treatment. Neither treatment improved
      asthma symptoms or quality of life. However, in patients not receiving inhaled
      corticosteroids, addition of low-dose theophylline significantly (p < 0.002)
      improved asthma control and symptoms as well as lung function. CONCLUSIONS:
      Neither montelukast nor low-dose theophylline lowered the EPAC rate of poor
      asthma control in patients with poorly controlled asthma despite improved lung
      function. For patients not using inhaled corticosteroids, low-dose theophylline
      improved asthma symptom control more than montelukast or placebo, and provides a
      safe and low-cost alternative asthma treatment.

PMID- 16998096
TI  - Brenner tumors of the ovary: sonographic and computed tomographic imaging
      features.
AB  - OBJECTIVE: The purpose of this study was to describe the sonographic appearance
      of ovarian Brenner tumors with computed tomographic (CT) correlation. METHODS:
      Twenty-two female patients (age range, 32-78 years; mean, 58 years) with 25
      ovarian Brenner tumors were identified from pathologic records from 1990 to 2005.
      Corresponding pathologic reports and images (17 sonographic and 14 CT) were
      reviewed independently. RESULTS: Tumors ranged in size from 0.3 to 12 cm (mean,
      2.5 cm); all were benign. Sixteen (64%) of 25 were found incidentally. Eight
      (36%) of 22 patients had a total of 12 associated benign ovarian neoplasms (1 was
      contralateral); 3 patients had bilateral Brenner tumors. Eight (47%) of 17 tumors
      were not seen on sonography, and 5 (36%) of 14 were not seen on CT. Of the tumors
      seen on imaging, most were solid (67% on sonography and 78% on CT). Four tumors
      appeared at least partially cystic, of which 3 had coexistent cystic ovarian
      lesions. CONCLUSIONS: Brenner tumors are most often solid neoplasms found
      incidentally and frequently seen in association with other benign ovarian
      epithelial neoplasms.

PMID- 16998095
TI  - Gene expression profiling of familial and sporadic interstitial pneumonia.
AB  - RATIONALE: Idiopathic interstitial pneumonia (IIP) and its familial variants are
      progressive and largely untreatable disorders with poorly understood molecular
      mechanisms. Both the genetics and the histologic type of IIP play a role in the
      etiology and pathogenesis of interstitial lung disease, but transcriptional
      signatures of these subtypes are unknown. OBJECTIVES: To evaluate gene expression
      in the lung tissue of patients with usual interstitial pneumonia or nonspecific
      interstitial pneumonia that was either familial or nonfamilial in origin, and to
      compare it with gene expression in normal lung parenchyma. METHODS: We profiled
      RNA from the lungs of 16 patients with sporadic IIP, 10 with familial IIP, and 9
      normal control subjects on a whole human genome oligonucleotide microarray.
      RESULTS: Significant transcriptional differences exist in familial and sporadic
      IIPs. The genes distinguishing the genetic subtypes belong to the same functional
      categories as transcripts that distinguish IIP from normal samples. Relevant
      categories include chemokines and growth factors and their receptors, complement
      components, genes associated with cell proliferation and death, and genes in the
      Wnt pathway. The role of the chemokine CXCL12 in disease pathogenesis was
      confirmed in the murine bleomycin model of lung injury, with C57BL/6(CXCR4+/-)
      mice demonstrating significantly less collagen deposition than C57BL/6(CXCR4+/+)
      mice. Whereas substantial differences exist between familial and sporadic IIPs,
      we identified only minor gene expression changes between usual interstitial
      pneumonia and nonspecific interstitial pneumonia. CONCLUSIONS: Taken together,
      our findings indicate that differences in gene expression profiles between
      familial and sporadic IIPs may provide clues to the etiology and pathogenesis of
      IIP.

PMID- 16998097
TI  - Application of the breast imaging reporting and data system final assessment
      system in sonography of palpable breast lesions and reconsideration of the
      modified triple test.
AB  - OBJECTIVE: The purpose of our study was to evaluate the utility of the American
      College of Radiology's Breast Imaging Reporting and Data System (BI-RADS)
      sonographic final assessment system and palpation-guided fine-needle aspiration
      (FNA) for evaluation of palpable breast lesions. METHODS: Our computerized
      database identified 160 palpable lesions of the breast in which follow-up
      palpation-guided FNA, targeted sonography, and pathologic confirmation were
      performed. We used BI-RADS sonographic data on all lesions. The sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of malignancy were calculated for sonography and palpation-guided FNA. Two-sample
      binomial proportion tests were used as the statistical analysis (P<.05). RESULTS:
      The FNA results were defined as benign, atypical cells, suspicious for
      malignancy, malignancy, and insufficiency. The sensitivity, specificity,
      accuracy, positive predictive value, and negative predictive value were 90.9%,
      82.7%, 84.3%, 57.7%, and 97.2%, respectively, on sonography and 75.8% to 90.9%,
      82.7% to 98.4%, 84.3% to 94.4%, 57.7% to 92.6%, and 93.9% to 97.2% on FNA. There
      was no statistically significant difference for sensitivity and negative
      predictive value between the two examinations. CONCLUSIONS: The diagnostic
      accuracy of sonography was similar to that of palpation-guided FNA for not
      missing the malignancy. Clinical application of FNA results can be difficult,
      especially when the result is insufficiency or atypical cells. Moreover, FNA is
      invasive and overlaps other procedures. Therefore, we conclude that sonography
      can replace palpation-guided FNA for diagnosis of palpable lesions of the breast
      when the BI-RADS sonographic final assessment system is used appropriately.

PMID- 16998098
TI  - Diagnostic values of sonography for assessment of sternal fractures compared with
      conventional radiography and bone scans.
AB  - OBJECTIVE: This study was prospectively undertaken to evaluate the diagnostic
      value of sonography for detection of sternal fractures. We compared sonographic,
      conventional radiographic, and bone scan examinations of sternal fractures.
      METHODS: Fifty consecutive patients (26 male and 24 female; mean age, 45.2 years)
      were evaluated. Conventional radiography and sonography were performed in all
      patients, and bone scans were performed in 39 patients. All patients had acute
      pain and tenderness in anterior midline chest areas. Sonography was performed by
      2 musculoskeletal radiologists within 1 to 2 days after admission. Patients
      underwent conventional radiography at admission and bone scans within 4 to 7 days
      after admission. Two radiologists reviewed all imaging findings by means of
      consensus. In addition, sonography was performed in 20 asymptomatic patients in a
      normal control group. RESULTS: Conventional radiography depicted sternal
      fractures in 12 of 50 patients. Sternal fractures were detected in 31 of 50
      patients on sonography. Fractures on sonography were located in the manubrium (8
      cases), upper sternal body (11 cases), mid sternal body (5 cases), and lower
      sternal body (7 cases). Bone scans showed sternal hot uptakes (accumulations of
      the radionuclide used) in 18 of 39 patients. In the control group, there were no
      bony defects or abnormal contours. CONCLUSIONS: We could detect sternal fractures
      more effectively with sonography than with conventional radiography and bone
      scans. In addition, sternal fracture locations showed relatively even
      distributions, and focal fractures in the manubrium were not easily detected on
      bone scans.

PMID- 16998099
TI  - Sonographically guided percutaneous needle biopsy of soft tissue masses with
      histopathologic correlation.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of
      sonographically guided percutaneous core biopsy of soft tissue masses. METHODS:
      We retrospectively reviewed the medical records of patients who underwent
      sonographically guided biopsy of soft tissue masses at our institution during a
      50-month period. Core biopsy histopathologic results were compared with surgical
      or clinical follow-up. RESULTS: One hundred eighty-three patients, 76 male and
      107 female, with a mean age of 48.5 years were included in the study. Thirteen
      patients had more than 1 biopsy, and the total number of biopsies performed was
      196. Five patients were lost to follow-up. Biopsy results were diagnostically
      accurate in 174 (91%) cases. Thirteen biopsies were inconclusive. No
      complications occurred. The overall sensitivity, specificity, positive predictive
      value, and accuracy in separating malignant from benign lesions were 97%, 99%,
      99%, and 98%, respectively. CONCLUSIONS: Sonographically guided core needle
      biopsy is an accurate and safe means to obtain tissue samples for the
      histopathologic diagnosis of soft tissue masses. It obviates the need for open
      biopsy and should be performed routinely for treatment planning.

PMID- 16998100
TI  - Sonographically guided percutaneous needle tenotomy for treatment of common
      extensor tendinosis in the elbow.
AB  - OBJECTIVE: Chronic tendinosis of the common extensor tendon of the lateral elbow
      can be a difficult problem to treat. We report our experience with
      sonographically guided percutaneous needle tenotomy to relieve pain and improve
      function in patients with this condition. METHODS: We performed sonographically
      guided percutaneous needle tenotomy on 58 consecutive patients who had persistent
      pain and disability resulting from common extensor tendinosis. Under a local
      anesthetic and sonographic guidance, a needle was advanced into the common
      extensor tendon, and the tip of the needle was used to repeatedly fenestrate the
      tendinotic tissue. Calcifications, if present, were mechanically fragmented, and
      the adjacent bony surface of the apex and face of the epicondyle were abraded.
      Finally, the fenestrated tendon was infiltrated with a solution containing
      corticosteroid mixed with bupivacaine. After the procedure, patients were
      instructed to perform passive stretches and to undergo physical therapy. During a
      subsequent telephone interview, patients answered questions about their
      experience, their functioning level, and their perceptions of procedure outcome.
      RESULTS: Fifty-five (95%) of 58 patients were contacted by telephone and agreed
      to participate in the study. Thirty-five (63.6%) of 55 respondents reported
      excellent outcomes, 16.4% good, 7.3% fair, and 12.7% poor. The average follow-up
      time from the date of the procedure to the date of the interview was 28 months
      (range, 17-44 months). No adverse events were reported; 85.5% stated that they
      would refer a friend or close relative for the procedure. CONCLUSIONS:
      Sonographically guided percutaneous needle tenotomy for lateral elbow tendinosis
      is a safe, effective, and viable alternative for patients in whom all other
      nonsurgical treatments failed.

PMID- 16998101
TI  - Sonographic measurement of achilles tendons in asymptomatic subjects: variation
      with age, body height, and dominance of ankle.
AB  - OBJECTIVE: This study was undertaken to evaluate the thickness, cross-sectional
      area, and length of Achilles tendons in asymptomatic subjects of different age
      groups and heights and between dominant and nondominant ankles. METHODS: High
      resolution sonographic examinations of Achilles tendons were performed in 40
      healthy subjects (14 men and 26 women). The subjects were categorized into 4 age
      groups: (1) 20 to 29 years, (2) 30 to 39 years, (3) 40 to 49 years, and (4) 50
      years or older. The thickness, cross-sectional area, and length of the Achilles
      tendons of both ankles were measured. All Achilles tendons were measured with the
      ankle in a relaxed, neutral position. RESULTS: There was no significant
      difference in the thickness and length of Achilles tendons among subjects of
      different age groups (P>.05). The Achilles tendon cross-sectional area of
      subjects 50 years or older was significantly larger than that of subjects in the
      younger age groups (P<.05). There was a positive correlation between the height
      of the subjects and the length, thickness, and cross-sectional area of the
      Achilles tendons; however, the correlation coefficient was low (r=0.07-0.28;
      P>.05). Dominance of ankles did not affect the thickness and length of the
      Achilles tendons, whereas the cross-sectional area of the tendons was
      significantly larger in the dominant ankles (P<.05). CONCLUSIONS: Sonography is a
      useful imaging tool in the evaluation of Achilles tendons. Normal variations of
      the tendon morphologic characteristics should be considered in the clinical
      diagnosis.

PMID- 16998102
TI  - Prevalence of upper extremity deep venous thrombosis diagnosed by color Doppler
      duplex sonography in cancer patients with central venous catheters.
AB  - OBJECTIVE: The purpose of this study was to review the literature concerning
      upper extremity deep venous thrombosis (UEDVT) diagnosed by color Doppler duplex
      sonography (CDDS) in cancer patients with indwelling central venous catheters
      (CVCs). METHODS: From computerized databases (MEDLINE and Ovid), relevant
      publications regarding CDDS of the upper limb veins in cancer patients with CVCs
      were reviewed. RESULTS: Patients with malignancy have a higher rate of
      thrombosis, which is increased by the presence of CVCs. Screening CDDS in
      asymptomatic patients showed CVC-related UEDVT in 11.7% to 44% of patients. In
      symptomatic cancer patients, the range was similar to the asymptomatic ones, 6.7%
      to 48%. The presence of a CVC almost doubled the incidence of UEDVT in
      symptomatic patients. Color Doppler duplex sonography is an accurate examination
      for the diagnosis of UEDVT, with sensitivity ranging from 78% to 100% and
      specificity ranging from 82% to 100%. The main obstacle for the diagnosis of
      UEDVT is the presence of overlying bones, making it difficult to visualize and
      impossible to directly assess by compression techniques. Color and spectral
      Doppler sonography and the use of small transducers aid in the diagnosis. When
      several parameters are evaluated in combination, CDDS is a reliable method for
      diagnosing CVC-related thrombosis. CONCLUSIONS: Great variability in the
      prevalence of catheter-related thrombosis in cancer patients has been reported,
      although it is uniformly higher compared with patients without cancer. Color
      Doppler duplex sonography is the modality of choice for the diagnosis of CVC
      related UEDVT in symptomatic cancer patients and for screening for asymptomatic
      thrombosis in this specific population.

PMID- 16998103
TI  - Measurement of volumetric flow.
AB  - OBJECTIVE: The purpose of this study was to evaluate a 3-dimensional (3D)
      sonographic method for the measurement of volumetric flow under conditions of
      known flow rates and Doppler angles. METHODS: A GE/Kretz Voluson 730 system (GE
      Healthcare, Milwaukee, WI) and RAB2-5 probe were used to acquire 3D Doppler
      measurements in a custom flow phantom. Blood-mimicking fluid circulated by a
      computer-controlled pump provided a range of flow velocities (2-15 mL/s). A 6
      axis positioning system maneuvered the ultrasound probe through a range of angles
      (40 degrees-70 degrees and 110 degrees -140 degrees) with respect to the tube
      (orthogonal to the tube being 90 degrees). Volume data sets were obtained
      spanning 29 degrees lateral and 20 degrees elevational angles encompassing the
      flow tube in a scanning time of less than 10 seconds. Power Doppler data were
      used to correct for partial volume effects. RESULTS: Using a single angle (110
      degrees) with respect to the flow tube, measured and actual volume flow rates
      were within the 95% confidence interval over the full range of flow rates. At
      flow rates of 5 and 10 mL/s, the measured volume flow rates were all within +/
      15% of actual values for the range of angles tested and also stayed within the
      95% confidence interval. CONCLUSIONS: Direct comparisons of volume flow rates
      estimated with 3D sonography and known flow rates showed that the method has good
      accuracy. Subsequent comparisons under pulsatile and in vivo conditions will be
      needed to verify this performance for clinical applications.

PMID- 16998104
TI  - Three-dimensional sonography of the endometrium and adjacent myometrium:
      preliminary observations.
AB  - OBJECTIVE: By evaluating a series of patients undergoing pelvic sonography with
      routine 2-dimensional (2D) as well as 3-dimensional (3D) reconstructed images in
      the coronal plane, we attempted to characterize the types of additional
      information that can be obtained. METHODS: Ninety randomly selected patients
      undergoing transvaginal pelvic sonography were imaged according to a standard 2D
      protocol. A 3D uterine volume was then acquired in the sagittal plane and
      reconstructed in the coronal plane. The endometrium and surrounding myometrium
      were evaluated for architecture, masses, the relationship of masses to the
      endometrial cavity, and the anatomic configuration of the cavity. RESULTS: Ninety
      one studies were obtained. Additional findings were obtained on the coronal view
      in 28 studies (30.8%). No additional findings were obtained in 63 studies
      (69.2%). Normal endometrial and myometrial findings were obtained by conventional
      2D imaging in 42 of 91 patients. Of this group, additional findings were shown in
      2 (5%) patients. Forty-nine of the 91 patients had abnormal findings by 2D
      imaging. Additional information was obtained in 26 (53%) of these patients. Added
      information included uterine anomalies, better definition of the endometrium,
      more accurate delineation and location of endometrial polyps, location of
      leiomyomas, visualization of cystic areas within the myometrium, and confirmation
      of the location of intrauterine devices. CONCLUSIONS: The 3D reconstructed view
      of the endometrium and adjacent myometrium appears to be most helpful after a
      conventional transvaginal study, showing abnormalities within the endometrium and
      myometrium but being of little added benefit if the conventional findings are
      normal.

PMID- 16998105
TI  - Sonography of the acetabular labrum: visualization of labral injuries during
      intra-articular injections.
AB  - OBJECTIVE: The purpose of this series was to describe the improved conspicuity in
      the sonographic appearance of acetabular labral injuries during routine
      sonographically guided intra-articular injections. METHODS: Sonographic
      examinations of patients undergoing routine sonographically guided intra
      articular hip injections were reviewed for evidence of labral injuries (n=21).
      Sonographic examinations were then correlated with magnetic resonance images of
      the ipsilateral hip when available (n=14). RESULTS: Before injection, 13
      acetabular labra had linear or irregular hypoechoic clefts or fissures through
      the normally hyperechoic fibrocartilaginous labrum, thought to represent tears.
      Eight of the labra showed a more globular alteration in morphologic
      characteristics, with diffuse thickening and irregularity. During intra-articular
      injection, the visualized injected fluid outlined the labrum, yielding a
      "sonoarthrographic effect," providing a fluid interface along the labral
      boundaries, and confirming the presence of a tear by imbibition of injected
      material into the defect with a resultant subjective improvement in the labral
      injury. CONCLUSIONS: Evaluating the labrum after injection may improve
      visualization of labral injuries, as a result of greater labral conspicuity.

PMID- 16998106
TI  - Detection of ovarian Sertoli-Leydig cell tumors exclusively by color Doppler
      sonography.

PMID- 16998107
TI  - Primary primitive neuroectodermal tumor of the breast.

PMID- 16998108
TI  - Development of a carcinoma in situ in a fibroadenoma: color Doppler sonographic
      demonstration.

PMID- 16998109
TI  - Metastatic breast lesion from thymic carcinoma.

PMID- 16998110
TI  - Cavernous hemangioma of the breast parenchyma with unusual features.

PMID- 16998111
TI  - Contrast-enhanced breast ultrasonography reveals an unusual breast tumor in a
      male patient with gynecomastia.

PMID- 16998112
TI  - Hydatid cyst of the breast mimicking inflammatory carcinoma and mastitis.

PMID- 16998113
TI  - Primary breast tuberculosis diagnosed by sonographically guided core-needle
      biopsy.

PMID- 16998114
TI  - Laparoscopic ultrasonography for localization of a retained appendicolith after
      appendectomy.

PMID- 16998115
TI  - Sonographic and clinical features of angioleiomyoma presenting as a painful
      Achilles tendon mass.

PMID- 16998116
TI  - Sonographic evaluation of a tibial periosteal ganglion with an intraosseous
      component.

PMID- 16998117
TI  - Quality assessment of CoaguChek point-of-care prothrombin time monitors:
      comparison of the European community-approved procedure and conventional external
      quality assessment.
AB  - BACKGROUND: There is a need for dependable quality assessment (QA) of the widely
      used CoaguChek point-of-care testing prothrombin time monitor. By use of the
      prescribed set of 5 CoaguChek certified international normalized ratio (INR) QA
      plasmas, we compared the reliability of the immediate QA of individual monitors
      described in the European Community-recommended Technology Implementation Plan
      with conventional external QA analysis. METHODS: Experienced staff tested
      CoaguChek point-of-care monitors in routine use for controlling oral
      anticoagulant dosage at 9 Netherlands Thrombosis Service Centres. Testing was
      performed with both the certified CoaguChek INR for a set of 5 QA individual
      plasmas from the Eur Con Action on Anticoag (ECAA) and conventional external QA
      analysis. RESULTS: Patients brought 523 CoaguChek monitors to our service centers
      for assessment. The proportion with unsatisfactory performance indicated by a 15%
      deviation from the ECAA set was compared with 15% deviation from overall median
      INR of all CoaguChek monitors in the survey, as in conventional QA analysis. The
      results were similar (20.3% and 18.5%, respectively). Interlot differences of
      CoaguChek test strips were detected, but the incidence of unsatisfactory
      performance was similar with both analyses, from 6.5% to 37.5% with the certified
      INR method and from 5.9% to 33.3% with the overall median analysis. CONCLUSIONS:
      The results validate the use of the European Action on Anticoagulation rapid
      single-instrument QA-specific procedure for CoaguChek users compared with the
      nonspecific conventional QA analysis that relies on deviation from the overall
      median INR.

PMID- 16998118
TI  - Information for authors: Is the advice regarding the reporting of residuals in
      regression analysis incomplete? Should Cook's distance be included?

PMID- 16998119
TI  - Macro thyrotropin-IgG complex causes factitious increases in thyroid-stimulating
      hormone screening tests in a neonate and mother.

PMID- 16998120
TI  - Increased serum concentrations of pigment epithelium-derived factor in patients
      with end-stage renal disease.

PMID- 16998121
TI  - Comparison of DNA array platform vs DNA sequencing as genetic diagnosis tools for
      familial hypercholesterolemia.

PMID- 16998122
TI  - False reduction in serum methadone concentrations by BD Vacutainer serum
      separator tubes (SSTTM).

PMID- 16998123
TI  - Apolipoprotein A5 S19W may play a role in dysbetalipoproteinemia in patients with
      the Apo E2/E2 genotype.

PMID- 16998124
TI  - Genetic and cellular toxicology of dental resin monomers.
AB  - Monomers are released from dental resin materials, and thus cause adverse
      biological effects in mammalian cells. Cytotoxicity and genotoxicity of some of
      these methacrylates have been identified in a vast number of investigations
      during the last decade. It has been well-established that the co-monomer
      triethylene glycol dimethacrylate (TEGDMA) causes gene mutations in vitro. The
      formation of micronuclei is indicative of chromosomal damage and the induction of
      DNA strand breaks detected with monomers like TEGDMA and 2-hydroxyethyl
      methacrylate (HEMA). As a consequence of DNA damage, the mammalian cell cycle was
      delayed in both G1 and G2/M phases, depending on the concentrations of the
      monomers. Yet, the mechanisms underlying the genetic and cellular toxicology of
      resin monomers have remained obscure until recently. New findings indicate that
      increased oxidative stress results in an impairment of the cellular pro- and anti
      oxidant redox balance caused by monomers. It has been demonstrated that monomers
      reduced the levels of the natural radical scavenger glutathione (GSH), which
      protects cell structures from damage caused by reactive oxygen species (ROS).
      Depletion of the intracellular GSH pool may then significantly contribute to
      cytotoxicity, because a related increase in ROS levels can activate pathways
      leading to apoptosis. Complementary, cytotoxic, and genotoxic effects of TEGDMA
      and HEMA are inhibited in the presence of ROS scavengers like N-acetylcysteine
      (NAC), ascorbate, and Trolox (vitamin E). Elevated intracellular levels of ROS
      can also activate a complex network of redox-responsive macromolecules, including
      redox-sensitive transcription factors like nuclear factor kappaB (NF-kappaB). It
      has been shown that NF-kappaB is activated probably to counteract HEMA-induced
      apoptosis. The induction of apoptosis by TEGDMA in human pulp cells has been
      associated with an inhibition of the phosphatidylinositol 3-kinase (PI3-K) cell
      survival signaling pathway. Although the details of the mechanisms leading to
      cell death, genotoxicity, and cell-cycle delay are not completely understood,
      resin monomers may be able to alter the functions of the cells of the oral
      cavity. Pathways regulating cellular homeostasis, dentinogenesis, or tissue
      repair may be modified by monomers at concentrations well below those which cause
      acute cytotoxicity.

PMID- 16998125
TI  - The role of sucrose in cariogenic dental biofilm formation--new insight.
AB  - Dental caries is a biofilm-dependent oral disease, and fermentable dietary
      carbohydrates are the key environmental factors involved in its initiation and
      development. However, among the carbohydrates, sucrose is considered the most
      cariogenic, because, in addition to being fermented by oral bacteria, it is a
      substrate for the synthesis of extracellular (EPS) and intracellular (IPS)
      polysaccharides. Therefore, while the low pH environment triggers the shift of
      the resident plaque microflora to a more cariogenic one, EPS promote changes in
      the composition of the biofilms' matrix. Furthermore, it has recently been shown
      that the biofilm formed in the presence of sucrose presents low concentrations of
      Ca, P(i), and F, which are critical ions involved in de- and remineralization of
      enamel and dentin in the oral environment. Thus, the aim of this review is to
      explore the broad role of sucrose in the cariogenicity of biofilms, and to
      present a new insight into its influence on the pathogenesis of dental caries.

PMID- 16998126
TI  - The Prx1 homeobox gene is critical for molar tooth morphogenesis.
AB  - The paired-related homeobox genes, Prx1 and Prx2, encode transcription factors
      critical for orofacial development. Prx1(-/-)/Prx2(-/-) neonates have mandibular
      hypoplasia and malformed mandibular incisors. Although the mandibular incisor
      phenotype has been briefly described (ten Berge et al., 1998, 2001; Lu et al.,
      1999), very little is known about the role of Prx proteins during tooth
      morphogenesis. Since the posterior mandibular region was relatively normal, we
      examined molar tooth development in Prx1(-/-)/Prx2(-/-) embryos to determine
      whether the tooth malformation is primary to the loss of Prx protein or secondary
      to defects in surrounding tissues. Three-dimensional (3D) morphological
      reconstructions demonstrated that Prx1(-/-)/Prx2(-/-) embryos had molar
      malformations, including cuspal changes and ectopic epithelial projections.
      Although we demonstrate that Prx1 protein is expressed only mesenchymally, 3D
      reconstructions showed important morphological defects in epithelial tissues at
      the cap and bell stages. Analysis of these data suggests that the Prx
      homeoproteins are critical for mesenchymal-epithelial signaling during tooth
      morphogenesis.

PMID- 16998127
TI  - Origin, splicing, and expression of rodent amelogenin exon 8.
AB  - Amelogenin RNA transcripts undergo extensive alternative splicing, and MMP-20
      processes the isoforms following their secretion. Since amelogenins have been
      ascribed cell-signaling activities, we asked if a lack of proteolytic processing
      by MMP-20 affects amelogenin signaling and consequently alters amelogenin splice
      site selection. RT-PCR analyses of amelogenin mRNA between control and Mmp20(-/
      )mice revealed no differences in the splicing pattern. We characterized 3
      previously unidentified amelogenin alternatively spliced transcripts and
      demonstrated that exon-8-encoded amelogenin isoforms are processed by MMP-20.
      Transcripts with exon 8 were expressed approximately five-fold less than those
      with exon 7. Analyses of the mouse and rat amelogenin gene structures confirmed
      that exon 8 arose in a duplication of exons 4 through 5, with translocation of
      the copy downstream of exon 7. No downstream genomic sequences homologous to
      exons 4-5 were present in the bovine or human amelogenin genes, suggesting that
      this translocation occurred only in rodents.

PMID- 16998128
TI  - Eugenol inhibits sodium currents in dental afferent neurons.
AB  - Although eugenol is widely used in dentistry, little is known about the molecular
      mechanisms responsible for its anesthetic properties. In addition to calcium
      channels, recently demonstrated by our group, there could be another molecular
      target for eugenol. Using a whole-cell patch-clamp technique, we investigated the
      effect of eugenol on voltage-gated sodium channel currents (I(Na)) in rat dental
      primary afferent neurons identified by retrograde labeling with a fluorescent dye
      in maxillary molars. Eugenol inhibited action potentials and I(Na) in both
      capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with
      capsazepine, a competitive antagonist of transient receptor potential vanilloid 1
      (TRPV1), failed to block the inhibitory effect of eugenol on I(Na), suggesting no
      involvement of TRPV1. Two types of I(Na), tetrodotoxin (TTX)-resistant and TTX
      sensitive I(Na), were inhibited by eugenol. Our results demonstrated that eugenol
      inhibits I(Na) in a TRPV1-independent manner. We suggest that I(Na) inhibition by
      eugenol contributes to its analgesic effect.

PMID- 16998129
TI  - Fluid shear stress inhibits TNFalpha-induced osteocyte apoptosis.
AB  - Bone tissue can adapt to orthodontic load. Mechanosensing in bone is primarily a
      task for the osteocytes, which translate the canalicular flow resulting from bone
      loading into osteoclast and osteoblast recruiting signals. Apoptotic osteocytes
      attract osteoclasts, and inhibition of osteocyte apoptosis can therefore affect
      bone remodeling. Since TNF-alpha is a pro-inflammatory cytokine with apoptotic
      potency, and elevated levels are found in the gingival sulcus during orthodontic
      tooth movement, we investigated if mechanical loading by pulsating fluid flow
      affects TNF-alpha-induced apoptosis in chicken osteocytes, osteoblasts, and
      periosteal fibroblasts. During fluid stasis, TNF-alpha increased apoptosis by
      more than two-fold in both osteocytes and osteoblasts, but not in periosteal
      fibroblasts. One-hour pulsating fluid flow (0.70 +/- 0.30 Pa, 5 Hz) inhibited (
      25%) TNF-alpha-induced apoptosis in osteocytes, but not in osteoblasts or
      periosteal fibroblasts, suggesting a key regulatory role for osteocyte apoptosis
      in bone remodeling after the application of an orthodontic load.

PMID- 16998130
TI  - Streptococcus salivarius promotes mucin putrefaction and malodor production by
      Porphyromonas gingivalis.
AB  - Although the contribution of the oral microbiota to oral malodor is well
      documented, the potential role of Gram-positive micro-organisms is unclear. In
      the current study, we tested the hypothesis that Gram-positive micro-organisms
      contribute to malodor production by deglycosylating oral glycoproteins, rendering
      them susceptible to subsequent proteolysis. To this end, we examined the effect
      of Streptococcus salivarius on Porphyromonas gingivalis-mediated putrefaction of
      a model glycoprotein (pig gastric mucin). Malodor was scored by two odor judges,
      and volatile sulfides were determined with the use of a sulfide monitor. Mucin
      degradation was followed by electrophoresis on SDS-PAGE. Results showed that the
      addition of S. salivarius or beta-galactosidase promoted mucin degradation and
      concomitant malodor production. Addition of glycosidic inhibitors (p-APTG and
      glucose) inhibited this process. These results suggest that Gram-positive micro
      organisms such as S. salivarius contribute to oral malodor production by
      deglycosylating salivary glycoproteins, thus exposing their protein core to
      further degradation by Gram-negative micro-organisms.

PMID- 16998131
TI  - Immunogenicity and persistence of a targeted anti-caries DNA vaccine.
AB  - We have previously reported that a targeted anti-caries DNA vaccine, pGJA-P,
      induced accelerated and increased antibody responses compared with a non-targeted
      anti-caries DNA vaccine. Recently, pGJA-P/VAX, a new targeted anti-caries DNA
      vaccine for human trials, was constructed by replacing the pCI vector used in the
      construction of pGJA-P with pVAX1, the only vector authorized by the US Food and
      Drug Administration in clinical trials. Here, we report on our exploration of the
      kinetics of the antibody responses generated following pGJA-P/VAX immunization
      and the persistence of pGJA-P/VAX at both the inoculation site and the draining
      lymph nodes. Intranasal vaccination of mice with pGJA-P/VAX induced strong
      antibody responses that lasted for more than 6 months. Furthermore, pGJA-P/VAX
      could still be detected at both the inoculation site and the draining cervical
      lymph nodes 6 months after immunization. Thus, the persistent immune responses
      are likely due to the DNA depot in the host, which acts as a booster
      immunization.

PMID- 16998132
TI  - Laser-fluoride effect on root demineralization.
AB  - Although the individual cariostatic effects of laser and fluoride have been
      shown, the combined effect of CO(2) laser and fluoride on root demineralization
      remains uncertain and was the main aim of this study. By using a pH-cycling
      system and Polarized Light Microscopy, we demonstrated the synergistic effect of
      fluoride combined with CO(2) laser treatment on reducing root demineralization.
      The mean lesion depths (in microm) for each group were 160 +/- 14 (Control), 113
      +/- 8 (Laser treatment alone), 111 +/- 6 (Fluoride treatment alone), and 25 +/- 7
      (Fluoride followed by laser treatment). A significant laser-enhanced fluoride
      uptake, characterized by the ToF-SIMS analysis, was revealed by the 37% and 400%
      increments in loosely and firmly bound fluorides (both p < 0.002) in laser
      irradiated areas, compared with the non-irradiated controls. In conclusion, there
      is a significant synergistic effect of combined CO(2) laser and fluoride
      treatment on the inhibition of root demineralization, possibly due to laser
      enhanced fluoride uptake in the root.

PMID- 16998133
TI  - The effectiveness of school dental screening: a cluster-randomized control trial.
AB  - Dental screening of children in schools is undertaken in many countries. There is
      no evidence that this activity is effective. The objective of our study was to
      determine if school dental screening of children reduces untreated disease or
      improves attendance at the population level. A four-arm cluster-randomized
      controlled trial was undertaken in the northwest of England. In total, 16,864
      children aged 6-9 years in 168 schools were randomly allocated to 3 test groups,
      which received screening according to different models, and a control, which
      received no intervention. There were no significant differences in caries
      increment in the primary and secondary dentitions or in the proportions of
      children attending a dentist after screening between the control group and the 3
      intervention arms. School dental screening delivered according to 3 different
      models was not effective at reducing levels of active caries and increasing
      attendance in the population under study.

PMID- 16998134
TI  - ART and conventional root restorations in elders after 12 months.
AB  - Successful use of atraumatic restorative treatment (ART) in children has been
      reported, but little information is available regarding its use in older adults.
      The hypothesis of this study was that survival rates of root restorations placed
      by both ART and the conventional technique were similar. Root-surface caries
      lesions in 103 institutionalized elders in Hong Kong were treated randomly by
      either: (1) the conventional approach-caries removed by dental burs, and the
      cavity filled with light-cured resin-modified glass ionomer; or (2) the ART
      approach-caries removed by hand instruments, and the cavity filled with
      chemically cured high-strength glass ionomer. In total, 84 conventional and 78
      ART restorations were placed. After 12 months, 63 conventional and 59 ART
      restorations were reviewed, and the respective 12-month survival rates were 91.7%
      and 87.0% (p > 0.05). It is concluded that the survival rates of both types of
      root restorations were high and similar.

PMID- 16998135
TI  - Salivary LL-37 secretion in individuals with Down syndrome is normal.
AB  - Antimicrobial peptides play an important role in the innate immune response.
      Deficiency in salivary LL-37 antimicrobial peptide has been implicated in
      periodontitis in patients with morbus Kostman syndrome. Down syndrome is
      associated with periodontitis, diminished salivary flow, and salivary
      immunoglobulin deficiency. In the present study, levels of LL-37 and its hCAP18
      precursor were measured in saliva samples from young individuals with Down
      syndrome and compared with levels in those from age-matched healthy controls. LL
      37 and human cathelicidin antimicrobial protein (hCAP18) were detected in whole
      but not in parotid saliva. hCAP18 was more abundant than LL-37. The
      concentrations of salivary hCAP18 and LL-37 were found to be higher in
      individuals with Down syndrome than in healthy controls, but their secretion
      rates were similar. We concluded that, while the adaptive immunity of individuals
      with Down syndrome is impaired at the oral mucosa, the secretion rate of the LL
      37 component of the innate immune system is normal.

PMID- 16998136
TI  - Novel IRF6 mutations in Chinese patients with Van der Woude syndrome.
AB  - Van der Woude syndrome (VWS) (OMIM 119300) is a dominantly inherited,
      developmental disorder that is characterized by pits and/or sinuses of the lower
      lip and a cleft lip and/or cleft palate. Mutations in the interferon regulatory
      factor 6 gene (IRF6) have been recently identified in patients with VWS, with
      more than 60 mutations reported. However, the VWS phenotype, IRF6 mutation
      genotypes, and their interrelationships in Chinese VWS patients have not been
      studied. Here, we report 11 Chinese families with variable clinical phenotypes of
      VWS and identified mutations in all patients. Of the 11 mutations, 8 appeared to
      be novel: CC5.6GT, T342A, 566delA, C748T, C756A, C989A, C1209G, and 1316delT.
      Seven mutations caused a change or loss of the IRF6 domain. The marked phenotypic
      variation may be caused by the action of certain modifier genes on IRF6 function.

PMID- 16998137
TI  - Chemical interaction of phosphoric acid ester with hydroxyapatite.
AB  - Among functional monomers used in contemporary dental adhesives, 10
      methacryloyloxydecyl dihydrogen phosphate (MDP) has been found to interact
      chemically with hydroxyapatite (HAp) most intensively and stably. This effect was
      thought to be the basis of the superior bonding effectiveness of MDP-based self
      etch adhesives to enamel/dentin. To elucidate fully the chemical interaction and
      reactivity of MDP with HAp, we used (31)P CP-MAS NMR spectroscopy and powder x
      ray diffraction. In an aqueous ethanol solution, Ca ions were leached from HAp to
      form, at short term, a MDP-calcium salt (CaMHP(2)) layered structure on the HAp
      surface. When MDP was allowed to interact for longer time (< 24 hrs),
      CaHPO(4).2H(2)O precipitated on top of this MDP-calcium salt layered structure.
      In conclusion, the intense chemical interaction of MDP with HAp must be ascribed
      to superficial dissolution of HAp induced by the MDP adsorption and subsequent
      deposition of MDP-calcium salt with a solubility lower than that of
      CaHPO(4).2H(2)O.

PMID- 16998138
TI  - Residual stress in composites with the thin-ring-slitting approach.
AB  - During polymerization, dental composites develop residual stresses that may
      compromise the marginal integrity and properties of the restorative. The
      objective of this study was to use the thin-walled ring-slitting method to
      measure and compare residual stresses. The hypotheses to be tested were that
      composites would generate different levels of residual stress based on their
      specific formulations and slitting times. Rings made from composites (Z100,
      Herculite, and Heliomolar) were cut at different times (10 min, 1 and 24 hrs)
      after being light-cured, and stress was measured. Residual stress was higher at
      the earlier cutting times, except for Heliomolar (alpha < 0.05). For the 10
      minute and one-hour cutting groups, stress followed this order: Z100 > Herculite
      > Heliomolar. Early slitting was better to capture residual stress, and the thin
      walled rings showed higher values than thick-walled rings and were better able to
      discriminate residual stress in composites.

PMID- 16998140
TI  - Magnification--a new look at a long-known optical property of dentin.
AB  - Light propagation in human dentin exhibits a strong directional dependence
      featuring the long-known optical magnification property. We hypothesized that
      this anisotropic effect is caused by multiple scattering at the dentin tubules,
      and not by fiberoptic effects, as had been previously assumed. We performed
      measurements of the transmitted intensity from dentin disks and compared them
      with Monte Carlo simulations of light propagation in dentin, considering the
      scattering by the tissue's microstructure. We found that the optical anisotropy
      of dentin can be fully explained with this model. We concluded that the
      magnification property of dentin is due to multiple scattering by the dental
      microstructure.

PMID- 16998139
TI  - Controlled release of chlorhexidine from UDMA-TEGDMA resin.
AB  - Chlorhexidine salts are available in various formulations for dental
      applications. This study tested the hypothesis that the release of chlorhexidine
      from a urethane dimethacrylate and triethylene glycol dimethacrylate resin system
      can be effectively controlled by the chlorhexidine diacetate content and pH. The
      filler concentrations were 9.1, 23.1, or 33.3 wt%, and the filled resins were
      exposed to pH 4 and pH 6 acetate buffers. The results showed that Fickian
      diffusion was the dominant release mechanism. The rates of release were
      significantly higher in pH 4 buffer, which was attributed to the increase of
      chlorhexidine diacetate solubility at lower pH. The higher level of filler
      loading reduced the degree of polymerization, leading to a greater loss of
      organic components and higher chlorhexidine release rates.

PMID- 16998141
TI  - Nutrition support in adult trauma patients.
AB  - Nutrition supplementation is paramount to the care of severely injured patients.
      Despite its widespread use in trauma patients, many areas of clinical practice
      remain controversial. The purpose of this paper is to critically review the
      literature studying the use of enteral vs parenteral nutrition (PN) and to
      provide the rationale for early enteral nutrition. Additional controversies
      confronting clinicians are reviewed, including the use of immune-enhancing agents
      and the optimal site for enteral nutrition delivery (gastric vs small
      intestinal). Evidence-based recommendations for clinical practice are presented
      when available.

PMID- 16998142
TI  - Energy expenditure and protein requirements after traumatic injury.
AB  - Traumatic injury induces hypermetabolism. The degree of hypermetabolism can be
      variable, depending on the type of injury, the degree of inflammation, body
      composition, age, and treatment regimens. To estimate metabolic rate in some
      types of injury, predictive equations have been published. Some of these
      equations have been tested in validation studies. For other types of injury,
      equations do not exist. Some expert panels have recommended measuring in lieu of
      estimating metabolic rate, though studies have not been performed to determine
      whether clinical outcome is affected by the method used to determine energy
      requirements. Traumatically injured patients are usually catabolic, but protein
      needs after traumatic injury continue to be debated. Some suggest that 1.5 g
      protein per kg body weight is adequate and that any additional protein is simply
      oxidized, adding to the nitrogen load to be excreted. Alternately, protein intake
      >2.0 g/kg body weight increases the absolute rate of body protein synthesis, and
      achievement of nitrogen balance has been associated with survival. Thus,
      provision of high-protein feeding to achieve nitrogen balance might be
      worthwhile, even if that balance is achieved at the cost of additional nitrogen
      production.

PMID- 16998143
TI  - Antioxidant micronutrients in major trauma and burns: evidence and practice.
AB  - There has been a growing interest in micronutrients as a result of their
      essential role in endogenous antioxidant defense mechanisms and immunity.
      Critically ill burn and trauma patients are characterized by an increased free
      radical production, which is proportional to the severity of the injury. In
      addition, they are at high risk of negative trace element balances, which
      contribute to the imbalance in endogenous antioxidant capacity and the extension
      of primary lesions. Although selenium, zinc, and vitamin C and E status are
      altered in all injured patients, patients with major burns are unique for having
      copper deficiency. In major burns, high-dose ascorbic acid for 24 hours achieves
      reduction of resuscitation fluid requirements by endothelial antioxidant
      mechanisms both in animal models and in 1 human trial. Supplementation trials in
      trauma and burns including selenium and zinc have shown that early provision of
      micronutrients improves recovery. Vitamin supplementation trials without selenium
      have not achieved definitive effects. The human studies show that reinforcing
      antioxidant defenses early in the course of major injury is rational and that
      substituting the large initial micronutrient losses of selenium and zinc is safe
      in trauma, as is the addition of copper in burns. The IV route seems the only way
      to deliver the doses required to obtain a clinical effect.

PMID- 16998144
TI  - Traumatic brain injury in the pediatric population.
AB  - Traumatic brain injury (TBI) is a common injury among children. Most TBIs are
      mild and do not require hospitalization. However, whether or not the patients
      require acute hospitalization, TBIs may have long-lasting consequences. There is
      little research on the nutrient needs of these patients, and recommendations are
      frequently based on data from adults with TBI. It is clear that calorie and
      protein needs are elevated with acute TBI. However, calorie needs are also
      decreased by therapies such as sedation, chemical paralysis, and barbiturate
      coma. Long-term calorie needs may be lower for "comatose" patients. Enteral
      feeding is preferred and possible for patients with TBI, though gastric feeding
      may be problematic in some patients. In the acute phase, patients with TBI can
      also have dysregulation of fluid and electrolyte balance, which may require
      alterations in nutrition care. Dysphagia is common after moderately severe TBI
      and requires a multidisciplinary approach for treatment. Future opportunities for
      research on pediatric TBI are numerous and may include ongoing clarification of
      macronutrient needs, as well as investigation into the roles of specific
      nutrients such as zinc, antioxidants, and anti-inflammatory compounds.

PMID- 16998145
TI  - Considerations in fluids and electrolytes after traumatic brain injury.
AB  - Appropriate fluid management of patients with traumatic brain injury (TBI)
      presents a challenge for many clinicians. Many of these patients may receive
      osmotic diuretics for the treatment of increased intracranial pressure or develop
      sodium disturbances, which act to alter fluid balance. However, establishment of
      fluid balance is extremely important for improving patient outcomes after
      neurologic injury. The use of hyperosmolar fluids, such as hypertonic saline, has
      gained significant interest because they are devoid of dehydrating properties and
      may have other beneficial properties for patients with TBI. Electrolyte
      derangements are also common after neurologic injury, with many having neurologic
      manifestations. In addition, the role of electrolyte abnormalities in the
      secondary neurologic injury cascade is being delineated and may offer a potential
      future therapeutic intervention.

PMID- 16998146
TI  - Early enteral nutrition after abdominal trauma: effects on septic morbidity and
      practicality.

PMID- 16998147
TI  - Modular protein supplements and their application to long-term care.
AB  - Modular protein supplements are added to either the diet or enteral formula to
      increase the protein or amino acid intakes of people who are nutritionally
      compromised. Protein supplements are aggressively marketed to long-term care
      clinicians because protein energy malnutrition and wounds are a common problem in
      this care setting. It can be challenging for clinicians to distinguish one
      product from another and to determine the best product for a specific application
      or nutrition care goal. Modular protein products can be sorted into 4 categories:
      (1) protein concentrates derived from a complete protein such as milk, soy, or
      eggs; (2) protein concentrates derived from collagen, either alone or in
      combination with a complete protein; (3) doses of 1 or more dispensable
      (nonessential) amino acids; and (4) hybrids of the complete or collagen-based
      proteins and amino acid dose. Modular protein supplements are generally provided
      either as a substrate for protein synthesis or as a source of 1 or more amino
      acids that may be conditionally indispensable (conditionally essential) under
      certain disease conditions. This review provides guidelines for the use of
      modular protein supplements according to their intended physiologic function and
      the assessment and nutrition care goals of the long-term care resident.

PMID- 16998148
TI  - Trans fatty acids and coronary heart disease.
AB  - Epidemiologic evidence has linked trans fatty acids (TFAs) in the diet to
      coronary heart disease in human populations. It has been estimated that dietary
      TFAs from partially hydrogenated oils may be responsible for between 30,000 and
      100,000 premature coronary deaths per year in the United States. Although it is
      known that TFAs increase low-density lipoprotein (LDL) cholesterol levels and
      decrease high-density lipoprotein (HDL) cholesterol levels (markers of coronary
      heart disease), there is little known about the mechanisms by which TFAs actually
      function at the cellular level. It is unknown what levels of TFAs are clinically
      significant and it is unclear how TFAs are associated with cardiac arrhythmias or
      sudden cardiac death. We hypothesize that TFAs affect membrane structure, thus
      altering enzymatic pathways that may subsequently induce cardiac arrhythmias and
      sudden death.

PMID- 16998149
TI  - Nationwide survey of hospital practices when compounding parenteral nutrition
      solutions in latex-allergic patients.
AB  - We surveyed 100 institutions in 50 states, varying in size from 50 to 1,000 beds.
      The purpose of this survey was to examine the policies and techniques hospitals
      used in confirming latex allergy (LA) in patients and preparing parenteral
      nutrition (PN) for LA patients. Our survey indicated that within the institutions
      in our study, many inpatient pharmacists do not use any defined method for
      confirming LA other than what is documented in the patient profile upon
      admission. Most inpatient pharmacies are not aware of any institutional policy
      concerning parenteral medications in LA patients, and some do not identify the
      importance of LA in preparing PN. It is apparent from the results of this survey
      that uniform guidelines or practice standards for this important issue should be
      developed. Although the publications on LA are numerous, they mostly deal with
      the exposure to latex gloves or latex devices. Knowledge of preparing parenteral
      medications for LA patients in the literature is minimal. It is also clear that
      awareness and knowledge of pharmacy personnel should be enhanced. Finally, we are
      hoping that this survey will send a clear message to pharmacy organizations to
      develop guidelines or pharmacy practice standards for this issue, and for health
      institutions to develop policies and make them available to their personnel.

PMID- 16998150
TI  - Nutrition status of patients during hospitalization, Tehran, Iran.
AB  - BACKGROUND: We assessed the nutrition status of patients on admission and
      monitored changes during hospitalization at Shariatri Educational Hospital,
      Tehran, Iran. METHODS: One hundred fifty-six randomly selected patients from 9
      different wards were assessed. Body mass index (BMI) and body composition (based
      on bioelectrical impedance) were measured on admission and discharge. A
      questionnaire was also completed to evaluate general physical, psychological, and
      living status of the patients. Medical records were audited to identify when
      nutrition consultation, nutrition support, and nutrition-related laboratory
      factors (serum levels of total lymphocyte count [TLC] and albumin) were ordered.
      Frequency and paired t-test were used to analyze data. RESULTS: Undernutrition
      (BMI <18.5 kg/m(2)) was present in 5.7% of the patients on admission, and severe
      undernutrition (BMI <16 kg/m(2)) existed in 0.6%. When discharged, 11% of
      patients were undernourished, and the prevalence of severe undernutrition
      increased to 1.3%. Average body weight and BMI decreased significantly during
      hospitalization (p < .001). Body composition analysis showed a significant
      reduction in body protein mass (p < .001). During hospitalization, body water
      percentile decreased and body fat percentile increased but not significantly.
      Only 1 patient was supported with parenteral nutrition (PN) and 1 with enteral
      nutrition. Orders for nutrition consultation were present in 1.9%, TLC levels in
      10.8%, and serum albumin levels in 7% of the patient medical records surveyed.
      CONCLUSIONS: Undernutrition increased in patients during hospitalization.
      According to the low rate of nutrition-related orders, one potential cause of
      worsening nutrition status may be inadequate medical staff awareness about the
      importance of nutrition in hospitalized patients.

PMID- 16998151
TI  - The history of nonsurgical enteral tube feeding access.
AB  - Specialized nutrition support, particularly enteral feeding, has been used for
      centuries. Technologic advancements have affected the provision of enteral
      feeding. Feeding solutions and devices, as well as the techniques to place the
      feeding devices, have evolved. This article reviews the history of bedside
      placement methods for short-term enteral access devices.

PMID- 16998152
TI  - 2005 American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Standards
      and Guidelines survey.
AB  - An online survey about the use and format of the American Society for Parenteral
      and Enteral Nutrition (A.S.P.E.N.) Standards and Guidelines documents was
      conducted. The survey was sent to A.S.P.E.N. members, and an acceptable number of
      responses were received (470, or 9% of those surveyed). Most respondents
      indicated an overall satisfaction with the standards and guidelines and suggested
      format changes, many of which will be incorporated into future guidelines and
      standards. The results of this survey are presented here for general interest.
      Changes in the process with which A.S.P.E.N. produces standards and guidelines
      are discussed.

PMID- 16998153
TI  - Lithium leads to an increased FRQ protein stability and to a partial loss of
      temperature compensation in the Neurospora circadian clock.
AB  - In many organisms, the presence of lithium leads to an increase of the circadian
      period length. In Neurospora crassa, it was earlier found that lithium results in
      a decrease of overall growth and increased circadian periods. In this article,
      the authors show that lithium leads to a reduction of FRQ degradation with
      elevated FRQ levels and to a partial loss of temperature compensation. At a
      concentration of 13 mM lithium, FRQ degradation is reduced by about 60% while,
      surprisingly, the activity of the 20S proteasome remains unaffected. Experiments
      and model calculations have shown that the stability of FRQ is dependent on its
      phosphorylation state and that increased FRQ protein stabilities lead to
      increased circadian periods, consistent with the observed increase of the period
      when lithium is present. Because in Neurospora the proteasome activity is
      unaffected by lithium concentrations that lead to significant FRQ stabilization,
      it appears that lithium acts as an inhibitor of kinases that affect
      phosphorylation of FRQ and other proteins. A competition between Li(+) and Mg(2+)
      ions for Mg(2+)-binding sites may be a mechanism to how certain kinases are
      inhibited by Li(+). A possible kinase in this respect is GSK-3, which in other
      organisms is known to be inhibited by lithium. The partial loss of temperature
      compensation in the presence of lithium can be understood as an increase in the
      overall activation energy of FRQ degradation. This increase in activation energy
      may be related to a reduction in FRQ phosphorylation so that more kinase
      activity, that is, higher temperature and longer times, is required to achieve
      the necessary amount of FRQ phosphorylation leading to turnover. Using a modified
      Goodwin oscillator as a semiquantitative model for the Neurospora clock, the
      effects of lithium can be described by adding lithium inhibitory terms of FRQ
      degradation to the model.

PMID- 16998154
TI  - Casein kinases I of the silkworm, Bombyx mori: their possible roles in circadian
      timing and developmental determination.
AB  - Doubletime (DBT), a homolog of casein kinase Iepsilon (CKIepsilon), is an
      essential circadian clock component and developmental regulator in Drosophila
      melanogaster. The authors cloned a dbt homolog from the silkworm, Bombyx
      mori(Bmdbt), and examined its spatial and temporal expression in comparison to a
      CKI[alpha] homolog (BmCKIalpha). Four Bmdbt splice variants and 2 BmCKIalpha
      splice variants were detected, and their expression patterns varied in different
      tissues. The level of Bmdbt transcript in the brain was constant under LD 12:12
      while those of BmCKIalpha transcripts fluctuated with a decrease at ZT12. In situ
      hybridization showed presumably identical distribution of dbt, CKIalpha, and per
      transcripts in the putative clock neurons of the head ganglia, as well as in the
      retina, where CKI-and PER-like immunoreactivities were colocalized, suggesting a
      possible involvement of both CKIs in the B. mori circadian system. Signals were
      detected at 4 Ia(1) neurons in each dorsolateral protocerebrum, 6 to 8 cells in
      the pars intercerebralis, about 6 cells in the suboesophageal ganglion, 2 neurons
      in the frontal ganglion, and most of the photoreceptors. All these cells
      contained dbt, CKIalpha, and per antisense transcripts. The Northern analysis of
      dbtand CKIalpha transcripts at different developmental stages showed that both
      genes were expressed at relatively high levels during early embryogenesis and in
      the ovary. The levels of CKIalpha transcripts were also high in the late larval
      stages until the mid-fifth instar and then suddenly disappeared before larval
      pupal ecdysis. In contrast, the transcriptional activity of both genes was low in
      diapausing eggs.

PMID- 16998155
TI  - Transcriptional profiling in the adrenal gland reveals circadian regulation of
      hormone biosynthesis genes and nucleosome assembly genes.
AB  - The master circadian pacemaker of the suprachiasmatic nuclei coordinates
      behavioral and physiological rhythms via synchronization of subordinate
      peripheral oscillators in the central nervous system and organs throughout the
      body. Among these organs, the adrenal glands hold a prime position because of
      their regulatory influence on numerous physiological functions via rhythmic
      secretion of catecholamines and corticoid hormones into the bloodstream. In this
      report, the authors perform whole genome microarray hybridization to characterize
      the circadian transcriptome of the murine adrenal. They show that ~5% of the
      mouse genome is under circadian control in this gland. Using gene ontology
      analysis, they identify classes of transcripts that may synchronize adrenal
      hormone production. The authors' expression profiling also revealed that multiple
      histone genes implicated in either DNA replication or transcriptional regulation
      are clock controlled, suggesting a novel way by which the circadian clock may
      regulate the chromatin state.

PMID- 16998156
TI  - Phase and period responses of the circadian system of mice (Mus musculus) to
      light stimuli of different duration.
AB  - To understand entrainment of circadian systems to different photoperiods in
      nature, it is important to know the effects of single light pulses of different
      durations on the free-running system. The authors studied the phase and period
      responses of laboratory mice (C57BL6J//OlaHsd) to single light pulses of 7
      different durations (1, 3, 4, 6, 9, 12, and 18 h) given once per 11 days in
      otherwise constant darkness. Light-pulse duration affected both amplitude and
      shape of the phase response curve. Nine-hour light pulses yielded the maximal
      amplitude PRC. As in other systems, the circadian period slightly lengthened
      following delays and shortened following advances. The authors aimed to
      understand how different parts of the light signal contribute to the eventual
      phase shift. When PRCs were plotted using the onset, midpoint, and end of the
      pulse as a phase reference, they corresponded best with each other when using the
      mid-pulse. Using a simple phase-only model, the authors explored the possibility
      that light affects oscillator velocity strongly in the 1st hour and at reduced
      strength in later hours of the pulse due to photoreceptor adaptation. They fitted
      models based on the 1-h PRC to the data for all light pulses. The best overall
      correspondence between PRCs was obtained when the effect of light during all
      hours after the first was reduced by a factor of 0.22 relative to the 1st hour.
      For the predicted PRCs, the light action centered on average at 38% of the light
      pulse. This is close to the reference phase yielding best correspondence at 36%
      of the pulses. The result is thus compatible with an initial major contribution
      of the onset of the light pulse followed by a reduced effect of light responsible
      for the differences between PRCs for different duration pulses. The authors
      suggest that the mid-pulse is a better phase reference than lights-on to plot and
      compare PRCs of different light-pulse durations.

PMID- 16998157
TI  - Interval timer control of puberty in photoinhibited Siberian hamsters.
AB  - Puberty, which is markedly delayed in male Siberian hamsters (Phodopus sungorus)
      born into short day lengths, is controlled by an interval timer regulated by the
      duration of nocturnal melatonin secretion. Properties of the interval timer were
      assessed by perturbing normal patterns of melatonin secretion in males gestated
      and maintained thereafter in 1 of 2 short day lengths, 10 h light/day (10 L) or
      12L. Melatonin secretion of short-day hamsters was suppressed by constant light
      treatment or modified by daily injection of propranolol to mimic nocturnal
      melatonin durations typical of long-day hamsters. Constant light treatment during
      weeks 3 to 5 induced early incomplete gonadal growth in 12L but not 10 L hamsters
      but did not affect late onset of gonadal development indicative of puberty in
      either photoperiod. Propranolol treatment during postnatal weeks 3 to 5 induced
      transient growth of the testes and ultimately delayed the timing of puberty by 3
      weeks. Similar treatments between weeks 5 and 7 or on alternate weeks for 24
      weeks did not affect the interval timer. The first 2 weeks after weaning may
      constitute a critical period during which the interval timer is highly responsive
      to photoperiod. Alternatively, the hamsters' photoperiodic history rather than
      age or developmental stage may be the critical variable. The interpolation of
      long-day melatonin signals at the time of weaning does not appear to reset the
      interval timer to its zero position but may reduce timer responsiveness to long
      day melatonin signals several weeks later.

PMID- 16998158
TI  - Photoperiod differentially affects immune function and reproduction in collared
      lemmings (Dicrostonyx groenlandicus).
AB  - Many nontropical rodent species experience predictable annual variation in
      resource availability and environmental conditions. Individuals of many animal
      species engage in energetically expensive processes such as breeding during the
      spring and summer but bias investment toward processes that promote survival such
      as immune function during the winter. Generally, the suite of responses
      associated with the changing seasons can be induced by manipulating day length
      (photoperiod). Collared lemmings (Dicrostonyx groenlandicus) are arvicoline
      rodents that inhabit parts of northern Canada and Greenland. Despite the extreme
      conditions of winter in their native habitat, these lemmings routinely breed
      during the winter. In the laboratory, collared lemmings have divergent responses
      to photoperiod relative to other seasonally breeding rodents; short day lengths
      can stimulate, rather than inhibit, the reproductive system. Male and female
      collared lemmings were maintained for 11 weeks in 1 of 3 photoperiods (LD 22:2,
      LD 16:8, or LD 8:16) that induce markedly different phenotypes. Following
      photoperiod treatment, cell-mediated immune function as assessed by delayed-type
      hypersensitivity reactions was elevated in lemmings housed in LD 16:8 and LD 8:16
      relative to LD 22:2. However, antibody production to a novel antigen was
      unaffected by photoperiod. Exposure to LD 8:16 induced weight gain, molt to a
      winter pelage, and in contrast to previous studies, regression of the male, but
      not the female, reproductive tract. In conclusion, these data indicate that
      components of immune function among collared lemmings are responsive to changes
      in day length.

PMID- 16998159
TI  - Dim light adaptation attenuates acute melatonin suppression in humans.
AB  - Abstract Studies in rodents with retinal degeneration indicated that neither the
      rod nor the cone photoreceptors obligatorily participate in circadian responses
      to light, including melatonin suppression and photoperiodic response. Yet there
      is a residual phase-shifting response in melanopsin knockout mice, which suggests
      an alternate or redundant means for light input to the SCN of the hypothalamus.
      The findings of Aggelopoulos and Meissl suggest a complex, dynamic
      interrelationship between the classic visual photoreceptors and SCN cell
      sensitivity to light stimuli, relative to various adaptive lighting conditions.
      These studies raised the possibility that the phototransductive physiology of the
      retinohypothalamic tract in humans might be modulated by the visual rod and cone
      photoreceptors. The aim of the following two-part study was to test the
      hypothesis that dim light adaptation will dampen the subsequent suppression of
      melatonin by monochromatic light in healthy human subjects. Each experiment
      included 5 female and 3 male human subjects between the ages of 18 and 30 years,
      with normal color vision. Dim white light and darkness adaptation exposures
      occurred between midnight and 0200 h, and a full-field 460-nm light exposure
      subsequently occurred between 0200 and 0330-h for each adaptation condition, at 2
      different intensities. Plasma samples were drawn following the 2-h adaptation, as
      well as after the 460-nm monochromatic light exposure, and melatonin was measured
      by radioimmunoassay. Comparison of melatonin suppression responses to
      monochromatic light in both studies revealed a loss of significant suppression
      after dim white light adaptation compared with dark adaptation (p < 0.04 and p <
      0.01). These findings indicate that the activity of the novel circadian
      photoreceptive system in humans is subject to subthreshold modulation of its
      sensitivity to subsequent monochromatic light exposure, varying with the
      conditions of light adaptation prior to exposure.

PMID- 16998160
TI  - Predicting regulation of the phosphorylation cycle of KaiC clock protein using
      mathematical analysis.
AB  - Abstract The cyanobacterial clock protein KaiC regulates the circadian cycle by
      exhibiting rhythms in transcription, translation, and phosphorylation. KaiC
      phosphorylation persists in circadian cycling even under transcription-less
      conditions and was reconstituted in vitro by incubating KaiC, KaiA, and KaiB.
      This presents a novel perspective for circadian oscillation occurring due to
      interactions between clock proteins. Using mathematical models, the authors
      investigated the mechanism for the transcription-less KaiC phosphorylation cycle.
      They developed a simple model based on the possible KaiC behavior, which is
      experimentally suggested by Kitayama et al. (2003, EMBO J, 22:2127-2134). They
      hypothesized that the KaiC-KaiA complex formation, followed by a decrease in free
      KaiA molecules, may attenuate the KaiC phosphorylation rate, and it acts as
      negative feedback in the system. However, this model was shown not to be adequate
      to generate the KaiC phosphorylation cycle. The authors developed the general
      version of the model and determined the necessary condition to generate the KaiC
      phosphorylation cycle. Linear stability analysis revealed that oscillations can
      occur when the distance of feedback between the recipient reaction and the
      effector is far enough. Furthermore, they classified negative feedback
      regulations in the closed system into 2 types: destabilizing inhibition and
      stabilizing inhibition. Based on this result, the authors predicted that, in
      addition to the identified states of KaiC, another unknown state must be present
      between KaiC phosphorylation and the complex formation. By incorporating the
      unknown state into the previous model, they realized the periodic pattern
      reminiscent of the KaiC phosphorylation cycle in computer simulation. This result
      implies that the KaiC-KaiA complex formation requires more than 1 step of
      posttranslational modification, including phosphorylation or conformational
      change of KaiC.

PMID- 16998161
TI  - How much of the decrease in cancer death rates in the United States is
      attributable to reductions in tobacco smoking?

PMID- 16998162
TI  - Mexico: backroom deal blunts health warnings.

PMID- 16998164
TI  - India: "low-risk" launch.

PMID- 16998168
TI  - Effects of preoperative smoking cessation on the incidence and risk of
      intraoperative and postoperative complications in adult smokers: a systematic
      review.
AB  - OBJECTIVES: To establish the effect of preoperative smoking cessation on the risk
      of postoperative complications, and to identify the effect of the timing of
      preoperative cessation. DATA SOURCES: The Cochrane Library Database, PsycINFO,
      EMBASE, Medline, and CINAHL databases were searched, using the terms: "smoking",
      "smoking-cessation", "tobacco-use", "tobacco-abstinence", "cigarett$",
      "complication$", "postoperative-complication$", "preoperative", "perioperative"
      and "surg$". Further articles were obtained from reference lists. The search was
      limited to articles on adults, written in English and published up to November
      2005. STUDY SELECTION: Prospective cohort designs exploring the effects of
      preoperative smoking cessation on postoperative complications were included. Two
      reviewers independently scanned abstracts of relevant articles to determine
      eligibility. Lack of agreement was resolved through discussion and consensus.
      Twelve studies met the inclusion criteria. DATA EXTRACTION: Methodological
      quality was assessed by both reviewers, exploring validation of smoking status,
      clear definition of the period of smoking cessation, control for confounding
      variables and length of follow-up. DATA SYNTHESIS: Only four of the studies
      specified the exact period of smoking cessation, with six studies specifying the
      length of the follow-up period. Five studies revealed a lower risk or incidence
      of postoperative complications in past smokers than current smokers or reported
      that there was no significant difference between past smokers and non-smokers.
      CONCLUSIONS: Longer periods of smoking cessation appear to be more effective in
      reducing the incidence/risk of postoperative complications; there was no
      increased risk in postoperative complications from short term cessation. An
      optimal period of preoperative smoking cessation could not be identified from the
      available evidence.

PMID- 16998169
TI  - Finding the Kool Mixx: how Brown & Williamson used music marketing to sell
      cigarettes.
AB  - OBJECTIVE: To describe the history of Kool's music-themed promotions and analyse
      the role that music played in the promotion of the brand. METHODS: Analysis of
      previously secret tobacco industry documents, legal documents, and promotional
      materials. RESULTS: Brown & Williamson started Kool sponsorship of musical events
      in 1975 with Kool Jazz concerts. Music was considered to be an effective
      marketing tool because: (1) music helped consumers make emotional connections
      with the brand; (2) music concerts were effective for targeted marketing; (3)
      music tied together an integrated marketing campaign; and (4) music had potential
      to appeal widely to a young audience. Brown & Williamson's first music campaigns
      successfully targeted young African-American male audiences. Subsequent campaigns
      were less effective, exploring different types of music to achieve a broader
      young adult appeal. CONCLUSIONS: This case study suggests Brown & Williamson used
      music most successfully for targeted marketing, but they failed to develop a
      wider audience using music because their attempts lacked consistency with the
      Kool brand's established identity. The 2004 "Kool Mixx" campaign both returned to
      Brown & Williamson's historic practice targeting young African-American males,
      and also exploited a musical genre with much more potential to bring Kool more
      universal appeal, as hip-hop music is increasingly popular among diverse
      audiences. Tobacco control efforts led by African-American community activists to
      oppose these marketing strategies should continue; expanding these coalitions to
      include the hip-hop community may further increase their effectiveness.

PMID- 16998170
TI  - US news media coverage of tobacco control issues.
AB  - OBJECTIVE: To characterise the relative amount and type of daily newspaper, local
      and national TV newscast, and national news magazine coverage of tobacco control
      issues in the United States in 2002 and 2003. DESIGN: Content analysis of daily
      newspapers, news magazines, and TV newscasts. SUBJECTS: Items about tobacco in
      daily newspapers, local and national TV newscasts, and three national news
      magazines in a nationally representative sample of 56 days of news stratified by
      day of week and season of the year, from 2002 and 2003. MAIN OUTCOME MEASURES:
      Story theme, tobacco topics, sources, story prominence, story valence
      (orientation), and story type. RESULTS: Tobacco coverage was modest over the two
      year period as estimated in our sample. Only 21 TV stories, 17 news magazine
      stories, and 335 daily newspaper stories were found during the two-year sampling
      period. Noteworthy results for the newspaper data set include the following: (1)
      government topics predominated coverage; (2) government action and negative
      health effects topics tended not to occur together in stories; (3) tobacco
      stories were fairly prominently placed in newspapers; (4) opinion news items
      tended to favour tobacco control policies, while news and feature stories were
      evenly split between positive and negative stories; and (5) tobacco coverage in
      the southeast, which is the country's major tobacco producing region, did not
      differ from the rest of the country. CONCLUSION: Results suggest mixed support in
      news coverage for tobacco control efforts in the United States. The modest amount
      of news coverage of tobacco is troubling, particularly because so few news
      stories were found on TV, which is a more important news source for Americans
      than newspapers. When tobacco was covered, government themed stories, which often
      did not include mentions of negative health effects, were typical, suggesting
      that media coverage does not reinforce the reason for tobacco control efforts.
      However, some results were encouraging. For example, when newspapers did cover
      tobacco, they accorded the stories relatively high prominence, thus increasing
      the chance that readers would see tobacco stories when they were published.

PMID- 16998171
TI  - Use of nicotine replacement therapy in socioeconomically deprived young smokers:
      a community-based pilot randomised controlled trial.
AB  - BACKGROUND: Smoking is common in young people, particularly in disadvantaged
      groups, and continued smoking has a major impact on quality and quantity of life.
      Although many young smokers want to stop smoking, little is known about the
      design and effectiveness of cessation services for them. OBJECTIVE: To determine
      whether nicotine replacement therapy (NRT) when combined with counselling is
      effective in young smokers in a deprived area of Nottingham, UK. METHODS AND
      SUBJECTS: We surveyed smoking prevalence and attitudes to smoking and quitting in
      young people accessing an open access youth project in a deprived area of
      Nottingham, and used the information gained to design a community based smoking
      cessation service incorporating a randomised controlled trial of nicotine patches
      against placebo given in association with individual behavioural support. We
      resurveyed smoking prevalence among project attendees after completing the pilot
      study. RESULTS: Of 264 young people surveyed (median age 14 years, range 11-21),
      49% were regular smokers. A total of 98 young people were recruited and
      randomised to receive either active nicotine patches on a six week reducing dose
      regimen (49 participants), or placebo (49 participants). Adherence to therapy was
      low, the median duration being one week, and 63 participants did not attend any
      follow up. At four weeks, five subjects receiving active NRT and two receiving
      placebo were abstinent, and at 13 weeks none were. Adverse effects were more
      common in the active group but none were serious. Smoking prevalence among 246
      youth project attendees surveyed after the trial was 44%. CONCLUSIONS: This study
      suggests that NRT in this context is unlikely to be effective in young smokers,
      not least because of low adherence to therapy. It also suggests that young
      smokers want help with smoking cessation, but that establishing the efficacy of
      smoking cessation services for young people who need them most will be very
      difficult.

PMID- 16998172
TI  - Tobacco point-of-purchase promotion: examining tobacco industry documents.
AB  - In the face of increasing media restrictions around the world, point-of-purchase
      promotion (also called point-of-sale merchandising, and frequently abbreviated as
      POP or POS) is now one of the most important tools that tobacco companies have
      for promoting tobacco products. Using tobacco industry documents, this paper
      demonstrates that tobacco companies have used point-of-purchase promotion in
      response to real or anticipated advertising restrictions. Their goal was to
      secure dominance in the retail setting, and this was achieved through well
      trained sales representatives who offered contracts for promotional incentive
      programmes to retailers, which included the use of point-of-sale displays and
      merchandising fixtures. Audit programmes played an important role in ensuring
      contract enforcement and compliance with a variety of tobacco company incentive
      programmes. Tobacco companies celebrated their merchandising successes, in
      recognition of the stiff competition that existed among tobacco companies for
      valuable retail display space.

PMID- 16998173
TI  - Smoking in immigrants: do socioeconomic gradients follow the pattern expected
      from the tobacco epidemic?
AB  - OBJECTIVES: Although socioeconomic patterns of smoking across the different
      stages of the tobacco epidemic have been well researched, less is known about
      these patterns among immigrant populations. This paper aims to assess the smoking
      prevalence and its socioeconomic gradients among three immigrant populations.
      METHODS: Three cross-sectional studies, using structured face-to-face interviews,
      were conducted in three representative (for socioeconomic status) samples of 385
      Turkish, 316 Moroccan, and 1072 Surinamese first-generation immigrants aged 35-60
      years in Amsterdam, The Netherlands. Information gathered included information
      about smoking behaviour, educational level and background characteristics. The
      associations between educational level and smoking rates were assessed using
      logistic regression analyses stratified by age and sex, for each ethnic group
      separately. RESULTS: The prevalence of smoking differed per group, being highest
      among Turkish and Surinamese men (63% and 55%, respectively), followed by
      Moroccan men and Turkish and Surinamese women (30%, 32% and 27%, respectively).
      Higher smoking rates were found among women with higher educational levels,
      except for Surinamese women aged 35-44 years. However, among Turkish and Moroccan
      men aged 35-44 years and Surinamese men, smoking rates were higher in lower
      socioeconomic groups. CONCLUSIONS: The prevalence figures and educational
      associations suggest that the socioeconomic gradient changes in earlier stages of
      the epidemic in immigrant populations than in the Western host populations,
      particularly in men. This provides indications to suggest that smoking prevention
      measures in male immigrant groups need to be tailored to lower socioeconomic
      groups in particular throughout the tobacco epidemic, and to higher socioeconomic
      groups among women.

PMID- 16998174
TI  - Adolescent snus use in Finland in 1981-2003: trend, total sales ban and
      acquisition.
AB  - OBJECTIVE: To study changes in adolescent snus use from 1981 to 2003, the effects
      of the total snus sales ban (1995) and snus acquisition. DESIGN: Biennial postal
      surveys in 1981-2003. SETTING AND PARTICIPANTS: Entire Finland; 12-, 14-, 16-,
      and 18-year-olds (n = 73,946; 3105-8390 per year). MAIN OUTCOME MEASURES: Snus
      use (experimental, daily/occasionally), snus acquisition (2001, 2003). RESULTS:
      Snus experimentation grew in popularity before the total sales ban in 16- and 18
      year-old boys and after the ban in all age and sex groups. A decrease was seen
      between 2001 and 2003, except for 18-year-old boys. Daily/occasional use mainly
      followed the same pattern in boys while in girls the daily/occasional use was
      rare and no significant changes were observed. In 2003, boys experimented with
      snus more often than girls (12-year-olds 1% v 0%, 14-year-olds 9% v 4%, 16-year
      olds 30% v 12%, 18-year-olds 44% v 18%). Hardly any girls used snus
      daily/occasionally, but 1% of 14-year-old boys, 7% of 16-year-olds, and 9% of 18
      year-olds did. Of daily/occasional users, 84% acquired snus from friends or
      acquaintances, 55% from tourist trips to neighbouring countries (Estonia,
      Sweden), and 7% through sport teams; 24% obtained it from under-the-counter
      sources. For experimenters, the corresponding figures were 79%, 18%, 0.3%, and
      5%. CONCLUSIONS: The total sales ban did not stop snus use; instead, the increase
      continued after the ban. Friends who travel to neighbouring countries act as go
      betweens reselling snus. Snus is used even by the youngest adolescents, thus
      contributing to the nicotine dependence process.

PMID- 16998175
TI  - Smokers and non-smokers talk about regulatory options in tobacco control.
AB  - OBJECTIVE: Community members are occasionally polled about tobacco control
      policies, but are rarely given opportunities to elaborate on their views. We
      examined laypeople's conversations to understand how 11 regulatory options were
      supported or opposed in interactions. DESIGN: Qualitative design; purposive quota
      sampling; data collection via focus groups. SETTING: Three locations in Sydney,
      Australia. PARTICIPANTS: 63 smokers and 75 non-smokers, men and women, from three
      age groups (18-24, 35-44, 55-64 years), recruited primarily via telephone.
      MEASUREMENTS: Semi-structured question route; data managed in NVivo; responses
      compared between groups. RESULTS: Laypeople rejected some regulatory proposals
      and certain arguments about taxation and the cost of cessation treatments.
      Protecting children and hypothecating tobacco excise for health education and
      care were highly acceptable. Plain packaging, banning retail displays and youth
      smoking prevention received qualified support. Bans on political donations from
      tobacco corporations were popular in principle but considered logistically
      fraught. Smokers asked for better cessation assistance and were curious about
      cigarette ingredients. Justice was an important evaluative principle. Support was
      often conditional and unresolved arguments frequent. We present both sides of
      these conflicts and the ways in which policies were legitimised or de-legitimised
      in conversation. CONCLUSIONS: Simple measures of agreement used in polls may
      obscure the complexity of community responses to tobacco policy. Support was
      frequently present but contested; some arguments that seem self-evident to
      advocates were not so to participants. The detailed understanding of laypeople's
      responses provided through qualitative methods may help frame proposals and
      arguments to meet concerns about justice, effectiveness and feasibility.

PMID- 16998176
TI  - The consequences of the unregulated cigarette.
AB  - This article considers changes in cigarette design in relation to the concept of
      "dose", drawing attention to the observation that there is not one smoking
      related epidemic of lung cancer, but at least two. Squamous carcinoma is
      declining in parallel with smoking prevalence while adenocarcinoma is increasing
      in the face of declining smoking prevalence. It is concluded that the
      adenocarcinoma epidemic is unnecessary and is due substantially to cigarette
      design changes, including increases in tobacco specific nitrosamines,
      manipulation of droplet size and ventilated filters. The need for regulation of
      smoke constituents is emphasised.

PMID- 16998177
TI  - Observed smoking in cars: a method and differences by socioeconomic area.
AB  - OBJECTIVES: To establish a reproducible method to estimate he point prevalence of
      smoking and second-hand smoke (SHS) exposure in cars, and to compare this
      prevalence between two areas of contrasting socioeconomic status. METHOD: A
      method involving two teams of observers was developed and evaluated. It involved
      observing 16,055 cars in Wellington, New Zealand. Two of the observation sites
      represented a high and a low area of deprivation (based on a neighbourhood
      deprivation index) and three were in the central city. RESULTS: A 4.1% point
      prevalence of smoking in cars was observed (95% confidence interval (CI) 3.8% to
      4.4%). There was a higher prevalence of smoking in cars in the high deprivation
      area relative to the other sites, and particularly compared to the low
      deprivation area (rate ratio relative to the latter 3.2, 95% CI 2.6 to 4.0). Of
      cars with smoking, 23.7% had other occupants being exposed to SHS. Cars with
      smoking and other occupants were significantly more likely to have a window open
      (especially if the smoker was not the driver). The observation method developed
      was practical, and inter-observer agreement was high (kappa value for the
      "smoking seen in car" category 0.95). CONCLUSIONS: Observational studies can be
      an effective way of investigating smoking in cars. The data from this survey
      suggest that smoking in cars occurs at a higher rate in relatively deprived
      populations and hence may contribute to health inequalities. Fortunately, there
      are a number of policy options for reducing SHS exposure in cars including mass
      media campaigns and laws for smoke-free cars.

PMID- 16998178
TI  - Tobacco imagery on New Zealand television 2002-2004.
AB  - Considerable emphasis has been placed on the importance of tobacco imagery in the
      movies as one of the "drivers" of smoking among young people. Findings are
      presented from a content analysis of 98 hours of prime-time programming on New
      Zealand television 2004, identifying 152 scenes with tobacco imagery, and
      selected characteristics of those scenes. About one in four programmes contained
      tobacco imagery, most of which might be regarded as "neutral or positive". This
      amounted to about two scenes containing such imagery for every hour of
      programming. A comparison with our earlier content analysis of programming in
      2002 indicated little change in the level of tobacco imagery. The effect of this
      imagery in contributing to young viewers taking up smoking, and sustaining the
      addiction among those already smoking, deserves more research attention.

PMID- 16998179
TI  - Stopping smoking: carpe diem?

PMID- 16998180
TI  - Environmental tobacco smoke exposure in motor vehicles: a preliminary study.

PMID- 16998181
TI  - Transduction of human embryonic stem cells by ecotropic retroviral vectors.
AB  - The steadily increasing availability of human embryonic stem (hES) cell lines has
      created strong interest in applying available tools for gene transfer in murine
      cells to human systems. Here we present a method for the transduction of hES
      cells with ecotropic retroviral vectors. hES cells were transiently transfected
      with a construct carrying the murine retrovirus receptor mCAT1. Subsequently, the
      cells were exposed to replication-deficient Moloney murine leukemia virus
      (MoMuLV) derivatives or pseudotyped lentiviral vectors. With oncoretroviral
      vectors, this procedure yields overall transduction efficiencies of up to 20% and
      permits selection of permanently transduced clones with high frequency. Selected
      clones maintained expression of pluripotency-associated markers and exhibited
      multi-germ layer differentiation both in vitro and in vivo. HES cell-derived
      somatic cells including neural progeny maintained high levels of transgene
      expression. Lentiviral vectors pseudotyped with the MoMuLV envelope could be
      introduced in the same manner with efficiencies of up to 33%. Transgene
      expression of lentivirally transduced hES cells remained permanent after
      differentiation even without selection pressure. Bypassing the regulatory issues
      associated with the use of amphotropic retroviral systems and exploiting the
      large pool of existing murine vectors, this method provides a safe and versatile
      tool for gene transfer and lineage analysis in hES cells and their progeny.

PMID- 16998182
TI  - Immunoprecipitation of spliceosomal RNAs by antisera to galectin-1 and galectin
      3.
AB  - We have shown that galectin-1 and galectin-3 are functionally redundant splicing
      factors. Now we provide evidence that both galectins are directly associated with
      spliceosomes by analyzing RNAs and proteins of complexes immunoprecipitated by
      galectin-specific antisera. Both galectin antisera co-precipitated splicing
      substrate, splicing intermediates and products in active spliceosomes. Protein
      factors co-precipitated by the galectin antisera included the Sm core
      polypeptides of snRNPs, hnRNP C1/C2 and Slu7. Early spliceosomal complexes were
      also immunoprecipitated by these antisera. When splicing reactions were
      sequentially immunoprecipitated with galectin antisera, we found that galectin-1
      containing spliceosomes did not contain galectin-3 and vice versa, providing an
      explanation for the functional redundancy of nuclear galectins in splicing. The
      association of galectins with spliceosomes was (i) not due to a direct
      interaction of galectins with the splicing substrate and (ii) easily disrupted by
      ionic conditions that had only a minimal effect on snRNP association. Finally,
      addition of excess amino terminal domain of galectin-3 inhibited incorporation of
      galectin-1 into splicing complexes, explaining the dominant-negative effect of
      the amino domain on splicing activity. We conclude that galectins are directly
      associated with splicing complexes throughout the splicing pathway in a mutually
      exclusive manner and they bind a common splicing partner through weak protein
      protein interactions.

PMID- 16998183
TI  - Covalent binding of the natural antimicrobial peptide indolicidin to DNA abasic
      sites.
AB  - Indolicidin is a host defense tridecapeptide that inhibits the catalytic activity
      of HIV-1 integrase in vitro. Here we have elucidated its mechanism of integrase
      inhibition. Using crosslinking and mass spectrometric footprinting approaches, we
      found that indolicidin interferes with formation of the catalytic integrase-DNA
      complex by directly binding DNA. Further characterization revealed that the
      peptide forms covalent links with abasic sites. Indolicidin crosslinks single- or
      double-stranded DNAs and various positions of the viral cDNA with comparable
      efficiency. Using truncated and chemically modified peptides, we show that abasic
      site crosslinking is independent of the PWWP motif but involves the indolicidin
      unique lysine residue and the N- and C- terminal NH2 groups. Because indolicidin
      can also inhibit topoisomerase I, we believe that multiple actions at the level
      of DNA might be a common property of antimicrobial peptides.

PMID- 16998184
TI  - Mechanisms of transcriptional regulation underlying temporal integration of
      signals.
AB  - How cells convert the duration of signals into differential adaptation of gene
      expression is a poorly understood issue. Signal-induced immediate-early gene
      (IEG) expression couples early signals to late expression of downstream <target>
      genes. Here we study how kinetic features of the IEG-<target> system allow
      temporal integration of stimuli in a pancreatic beta cell model of metabolic
      stimulation. Gene expression profiling revealed that beta cells produce
      drastically different transcriptional outputs in response to different stimuli
      durations. Noteworthy, most genes (87%) regulated by a sustained stimulation (4
      h) were not regulated by a transient stimulation (1 h followed by 3 h without
      stimulus). We analyzed the induction kinetics of several previously identified
      IEGs and <targets>. IEG expression persisted as long as stimulation was
      maintained, but was rapidly lost upon stimuli removal, abolishing the delayed
      <target> induction. The molecular mechanisms coupling the duration of stimuli to
      quantitative <target> transcription were demonstrated for the AP-1 transcription
      factor. In conclusion, we propose that the network composed of IEGs and their
      <targets> dynamically functions to convert signal inputs of different durations
      into quantitative differences in global transcriptional adaptation. These
      findings provide a novel and more comprehensive view of dynamic gene regulation.

PMID- 16998185
TI  - Inventory and analysis of the protein subunits of the ribonucleases P and MRP
      provides further evidence of homology between the yeast and human enzymes.
AB  - The RNases P and MRP are involved in tRNA and rRNA processing, respectively. Both
      enzymes in eukaryotes are composed of an RNA molecule and 9-12 protein subunits.
      Most of the protein subunits are shared between RNases P and MRP. We have here
      performed a computational analysis of the protein subunits in a broad range of
      eukaryotic organisms using profile-based searches and phylogenetic methods. A
      number of novel homologues were identified, giving rise to a more complete
      inventory of RNase P/MRP proteins. We present evidence of a relationship between
      fungal Pop8 and the protein subunit families Rpp14/Pop5 as well as between fungal
      Pop6 and metazoan Rpp25. These relationships further emphasize a structural and
      functional similarity between the yeast and human P/MRP complexes. We have also
      identified novel P and MRP RNAs and analysis of all available sequences revealed
      a K-turn motif in a large number of these RNAs. We suggest that this motif is a
      binding site for the Pop3/Rpp38 proteins and we discuss other structural features
      of the RNA subunit and possible relationships to the protein subunit repertoire.

PMID- 16998186
TI  - Inducible microRNA expression by an all-in-one episomal vector system.
AB  - Here we describe an episomal, one-vector system which allows the generation of
      cell populations displaying homogenous, inducible gene inactivation by RNA
      interference in a one step procedure. A dual tet-repressor/activator system
      tightly controls a bi-directional promoter, which simultaneously drives
      expression of microRNAs and a fluorescent marker protein. We demonstrate the
      effectiveness of this vector by knockdown of p53 expression in a human cell line
      which resulted in the expected loss of G1-arrest after DNA damage. The generation
      of a cell pool homogenously expressing the ectopic microRNAs was achieved in 1
      week without the need for viral infections. Induction of microRNA expression did
      not elicit an interferon response. Furthermore, the vector was adapted for
      convenient ligation-free transfer of microRNA cassettes from public libraries.
      This conditional knockdown-system should prove useful for many research and gene
      therapeutic applications.

PMID- 16998188
TI  - Advantages of hiring a radiologist assistant.

PMID- 16998187
TI  - NMR solution structure of the major G-quadruplex structure formed in the human
      BCL2 promoter region.
AB  - BCL2 protein functions as an inhibitor of cell apoptosis and has been found to be
      aberrantly expressed in a wide range of human diseases. A highly GC-rich region
      upstream of the P1 promoter plays an important role in the transcriptional
      regulation of BCL2. Here we report the NMR solution structure of the major
      intramolecular G-quadruplex formed on the G-rich strand of this region in K+
      solution. This well-defined mixed parallel/antiparallel-stranded G-quadruplex
      structure contains three G-tetrads of mixed G-arrangements, which are connected
      with two lateral loops and one side loop, and four grooves of different widths.
      The three loops interact with the core G-tetrads in a specific way that defines
      and stabilizes the overall G-quadruplex structure. The loop conformations are in
      accord with the experimental mutation and footprinting data. The first 3-nt loop
      adopts a lateral loop conformation and appears to determine the overall folding
      of the BCL2 G-quadruplex. The third 1-nt double-chain-reversal loop defines
      another example of a stable parallel-stranded structural motif using the G3NG3
      sequence. Significantly, the distinct major BCL2 promoter G-quadruplex structure
      suggests that it can be specifically involved in gene modulation and can be an
      attractive target for pathway-specific drug design.

PMID- 16998189
TI  - Alternate trauma shoulder projection.

PMID- 16998190
TI  - The blob, the line and the shadow.

PMID- 16998191
TI  - Agenesis of the corpus callosum: neonatal sonographic detection.
AB  - CONTEXT: Agenesis of the corpus callosum is a rare congenital midline brain
      abnormality that can disrupt normal cognitive progression. Primary complete
      agenesis usually occurs earlier in embryologic development, while partial
      agenesis occurs in later gestation. Agenesis of the corpus callosum has an
      estimated incidence ranging from 0.03% to 0.7% in the general population and is
      considered to be a component of as many as 50 to 200 different syndromes.
      OBJECTIVE: The purpose of this article is to summarize recent literature
      pertaining to the diagnosis of agenesis of the corpus callosum, including
      etiology, prognosis and the use of diagnostic medical sonography in the detection
      of this abnormality during the neonatal period. RESULTS: Agenesis of the corpus
      callosum can be easily detected with diagnostic medical sonography when a
      thorough evaluation of midline structures is performed. SUMMARY: A thorough
      understanding of related anomalies, an inclusive imaging protocol and the
      combination of critical thinking with investigative imaging will ensure that the
      diagnosis of agenesis of the corpus callosum can be accurately established.

PMID- 16998192
TI  - Collaborative learning in radiologic science education.
AB  - CONTEXT: Radiologic science is a complex health profession, requiring the
      competent use of technology as well as the ability to function as part of a team,
      think critically, exercise independent judgment, solve problems creatively and
      communicate effectively. OBJECTIVE: This article presents a review of literature
      in support of the relevance of collaborative learning to radiologic science
      education. In addition, strategies for effective design, facilitation and
      authentic assessment of activities are provided for educators wishing to
      incorporate collaborative techniques into their program curriculum. RESULTS: The
      connection between the benefits of collaborative learning and necessary workplace
      skills, particularly in the areas of critical thinking, creative problem solving
      and communication skills, suggests that collaborative learning techniques may be
      particularly useful in the education of future radiologic technologists. SUMMARY:
      This article summarizes research identifying the benefits of collaborative
      learning for adult education and identifying the link between these benefits and
      the necessary characteristics of medical imaging technologists.

PMID- 16998193
TI  - Contrast studies.
AB  - Contrast media plays an important role in imaging soft tissues and organs. Though
      contrast imaging is considered safe, radiologic technologists can improve the
      safety of contrast examinations by reviewing institutional safety procedures,
      safe practices for different methods of contrast administration and possible
      complications. The need for efficient communication and attention to detail
      during contrast procedures is essential for patient safety.

PMID- 16998194
TI  - Radiofrequency ablation of liver and lung tumors.
AB  - Radiofrequency ablation (RFA) is a procedure in which radiofrequency energy is
      used to heat and destroy abnormal tissue. This article discusses the evolution of
      RFA and its use to treat liver and lung tumors.

PMID- 16998197
TI  - MR and internal derangement.

PMID- 16998198
TI  - Computed tomography.

PMID- 16998199
TI  - Identification of proinflammatory flagellin proteins in supernatants of Vibrio
      cholerae O1 by proteomics analysis.
AB  - The genome of Vibrio cholerae contains five flagellin genes that encode proteins
      (FlaA-E) of 39-41 kDa with 61-82% identity among them. Although the existing live
      oral attenuated vaccine strains against cholera are protective in humans, there
      is an intrinsic residual cytotoxic and inflammatory component associated with
      these candidate vaccine strains. Bacterial flagellins are known to be potent
      inducers of proinflammatory molecules via activation of Toll-like receptor 5.
      Here we found that purified flagella from wild type V. cholerae 395 induced
      significant release of interleukin (IL)-8 from cultured HT-29 human colonic
      epithelial cells. Furthermore we found that filtered supernatants of KKV90, a
      DeltaflaA isogenic strain unable to produce flagella, were still able to activate
      production of IL-8 albeit to significantly lower levels than the wild type,
      suggesting that other activators of proinflammatory molecules were still present
      in these supernatants. A comparative proteomics analysis of secreted proteins of
      V. cholerae 395 and KKV90 identified additional proteins with potential to induce
      IL-8 release in HT-29 cells. Secreted proteins in the range of 30-45 kDa
      identified by two-dimensional electrophoresis and mass spectrometry revealed the
      presence of two additional flagellins, FlaC and FlaD, that appeared to be
      secreted 3- and 6-fold more, respectively, in the mutant compared with the wild
      type. Double isogenic mutants flaAC and flaAD were unable to trigger IL-8 release
      from HT-29 cells. In sum, we have shown that purified flagella and secreted
      flagellin proteins (FlaC and FlaD) are inducers of IL-8 release from epithelial
      cells via Toll-like receptor 5. This observation may explain, in part, the
      observed reactogenicity of cholera vaccine strains in humans.

PMID- 16998200
TI  - Sequence dependence of renucleation after a Gly mutation in model collagen
      peptides.
AB  - Missense mutations in the collagen triple helix that replace one Gly residue in
      the (Gly-X-Y)(n) repeating pattern by a larger amino acid have been shown to
      delay triple helix folding. One hypothesis is that such mutations interfere with
      the C- to N-terminal directional propagation and that the identity of the
      residues immediately N-terminal to the mutation site may determine the delay time
      and the degree of clinical severity. Model peptides are designed to clarify the
      role of tripeptide sequences N-terminal to the mutation site, with respect to
      length, stability, and nucleation propensity, to complete triple helix folding.
      Two sets of peptides with different N-terminal sequences, one with the natural
      sequence alpha1(I) 886-900, which is just adjacent to the Gly(901) mutation, and
      one with a GPO(GAO)(3) sequence, which occurs at alpha1(I) 865-879, are studied
      by CD and NMR. Placement of the five tripeptides of the natural alpha1(I)
      collagen sequence N-terminal to the Gly to Ala mutation site results in a peptide
      that is folded only C-terminal to the mutation site. In contrast, the presence of
      the Hyp-rich sequence GPO(GAO)(3) N-terminal to the mutation allows complete
      refolding in the presence of the mutation. The completely folded peptide contains
      an ordered central region with unusual hydrogen bonding while maintaining
      standard triple helix structure at the N- and C-terminal ends. These peptide
      results suggest that the location and sequences of downstream regions favorable
      for renucleation could be the key factor in the completion of a triple helix N
      terminal to a mutation.

PMID- 16998201
TI  - Disruption of phospholipase Cdelta4 gene modulates the liver regeneration in
      cooperation with nuclear protein kinase C.
AB  - Phospholipase Cdelta4 (PLC delta4) gene has been cloned from the cDNA library of
      regenerating rat liver. Using PLC delta4 gene-disrupted mice (PLC delta4(-/-)),
      we studied a role of PLC delta4 during liver regeneration after partial
      hepatectomy (PH). In PLC delta4(-/-), liver regeneration occurred in an
      apparently normal way. However, BrdU-indices indicated that PLC delta4 gene
      disruption delayed the onset of DNA synthesis by 2 h. Noticeably, the BrdU
      indices in PLC delta4(+/+) remained rather constant throughout S phase, 25-35%,
      whereas in PLC delta4(-/-), it fluctuated drastically from 25% at 34 h to 65% at
      late S, 42 h after PH. This fact showed that PLC delta4 gene disruption caused a
      higher synchronization of cell proliferation. The mRNA for PLC delta4 in PLC
      delta4(+/+) appeared at late G1, and the expression continued throughout S phase.
      PLC activity increased transiently in chromatin at the late G1 and S phases in
      only PLC delta4(+/+), but not in PLC delta4(-/-). The specific increases in PLC
      activity well correlated with the transient increases of protein kinase C (PKC)
      alpha in chromatin of PLC delta4(+/+). PKC epsilon also increased transiently in
      chromatin from PLC delta4(+/+) at late S. It is concluded that PLC delta4
      regulates the liver regeneration in cooperation with nuclear PKC alpha and
      epsilon.

PMID- 16998202
TI  - Polyamine analogs with xylene rings induce antizyme frameshifting, reduce ODC
      activity, and deplete cellular polyamines.
AB  - Numerous studies have correlated elevated polyamine levels with abnormal or rapid
      cell growth. One therapeutic strategy to treat diseases with increased cellular
      proliferation rates, most obviously cancer, has been to identify compounds which
      lower cellular polyamine levels. An ideal target for this strategy is the protein
      antizyme-a negative regulator of polyamine biosynthesis and import, and a
      positive regulator of polyamine export. In this study, we have optimized two
      tissue-culture assays in 96-well format, to allow the rapid screening of a 750
      member polyamine analog library for compounds which induce antizyme frameshifting
      and fail to substitute for the natural polyamines in growth. Five analogs (MQTPA1
      5) containing xylene (1,4-dimethyl benzene) were found to be equal to or better
      than spermidine at stimulating antizyme frameshifting and were inefficient at
      rescuing cell growth following polyamine depletion. These compounds were further
      characterized for effects on natural polyamine levels and enzymes involved in
      polyamine metabolism. Finally, direct measurements of antizyme induction in cells
      treated with two of the lead compounds revealed an 8- to 15-fold increase in
      antizyme protein over untreated cells. The impact of the xylene moiety and the
      distance between the positively charged amino groups on antizyme frameshifting
      and cell growth are discussed.

PMID- 16998203
TI  - Assessment of sun protection for children's summer 2005 clothing collection.
AB  - Overexposure to solar ultraviolet radiation (UVR) in childhood is considered to
      be a critical factor for developing skin cancer in later life. Clothing may offer
      a simple and effective means of protection against overexposure to the sun, but
      its use has often been underrated in public opinion. The Health Protection
      Agency, in close collaboration with a number of UK retailers, conducted a study
      to evaluate the UVR protection characteristics of the summer 2005 collection of
      children's clothing for outdoor activity. The current paper presents a summary of
      the assessment and the effects of stretching and wetting on the Ultraviolet
      Protection Factor (UPF) rating of children's clothing. The results demonstrate
      the need for better public guidance in sun protection of children and more
      comprehensive evaluation procedures for sun protection provided by clothing.

PMID- 16998204
TI  - X reference radiation qualities produced with tube voltages above 300 kV for the
      calibration and testing of dosemeters.
AB  - In the international standard ISO 4037-1, only X reference radiation qualities
      produced with tube voltages of up to 300 kV and with mean photon energies of
      lower than 250 keV are defined. Higher energy reference photon fields are given
      with a mean energy only from 662 keV (S-Cs) upwards. To close this energy gap,
      four new X radiation qualities, produced with tube voltages of 350 kV and 400 kV,
      were realised. The filtration of two of these qualities-called N-350 and N-400
      was chosen in such a way that they agree with the specifications of the narrow
      spectrum series (N-series) defined in ISO 4037-1. The other qualities which have
      been created-called H-350 and H-400-can be assigned to the high air-kerma rate
      series (H-series). The fluence spectra of these qualities were measured by using
      X-ray spectrometry. The values of 23 characteristic parameters were determined
      and compared with the ISO specifications for X-ray reference fields.

PMID- 16998205
TI  - Changes in cardiovascular risk factors among adolescents from 1995 to 2004 in the
      Republic of Karelia, Russia.
AB  - BACKGROUND: In Russia, cardiovascular mortality is among the highest in the
      world. Behaviours related to the development of cardiovascular disease are
      usually adopted in childhood and adolescence. Very little information exists on
      prevalence and trends of risk factors among Russian youth. This study aims to
      investigate changes in the prevalence of cardiovascular risk factors among
      adolescents in the Republic of Karelia, Russia, from 1995 to 2004. METHODS: Cross
      sectional surveys on chronic disease risk factors were carried out among 15-year
      old adolescents in Pitkaranta region, in the Republic of Karelia. The surveys
      were conducted in all 10 secondary schools in the Pitkaranta region. All ninth
      grade students in 1995 (N = 385, response rate 95%) and in 2004 (N = 395,
      response rate 85%) were included in the survey samples. RESULTS: Systolic blood
      pressure decreased statistically significantly among boys (from 119 to 116 mmHg).
      Diastolic blood pressure decreased statistically significantly among both girls
      (from 64 to 59 mmHg) and boys (from 62 to 59 mmHg). Total cholesterol increased
      statistically significantly only among girls (from 3.9 to 4.1 mmol/l). Body mass
      index did not exhibit any significant changes in both genders. Daily smoking rate
      doubled statistically significantly among girls from 7% to 15%. CONCLUSION: The
      study results show changes in the prevalence of cardiovascular disease risk
      factors among adolescents in the Republic of Karelia occurring over the last
      decade. Active measures need to be taken to prevent the increase in smoking
      prevalence, especially among girls, and to avert the unfavourable development of
      other risk factors in the future.

PMID- 16998206
TI  - The principle of precaution-based prevention: a Popperian paradox?

PMID- 16998207
TI  - Is the occurrence of back pain in Germany decreasing? Two regional postal surveys
      a decade apart.
AB  - BACKGROUND: Back pain is often perceived as an epidemic disorder with an ever
      increasing prevalence. The objective of this paper is to estimate and compare
      point and period prevalence rates of back pain from two highly comparable postal
      surveys, a decade apart within a single regional population in the north of
      Germany. METHODS: In 1991/1992 and 2003 two systematic random samples of German
      residents of Lubeck aged 25-74 years were independently drawn from the municipal
      population registry. They received a short postal questionnaire with maximally
      two reminders. All data were directly standardised on the age, sex, and
      educational distribution of the merged samples. A sharp decrease in response
      rates from 81% in the early 1990s to 60% in 2003 required complex considerations
      of non-response bias. RESULTS: Both the overall and gender-specific point and 1
      year prevalence rates of back pain remained fairly stable as well as the rate of
      severe disabling back pain. The overall prevalence (adjusted for age, sex, and
      education) of 'back pain today' was 39.2% (1991/92) and 38.2% (2003), the 1 year
      prevalence was 75.3% (1991/92) and 73.8% (2003), and the prevalence of severe
      pain was 9.9% (1991/92) and 10.2% (2003). CONCLUSIONS: The data do not support
      the widespread public notion of a growing epidemic of back pain in Germany.

PMID- 16998209
TI  - Clinical relevance of laboratory-reported antibiotic resistance in acute
      uncomplicated urinary tract infection in primary care.
AB  - OBJECTIVES: To determine whether patients with an uncomplicated community
      acquired urinary tract infection (UTI) and an isolate resistant to trimethoprim
      had worse clinical outcomes following empirical treatment with trimethoprim 200
      mg twice daily for 3 days than did those with a susceptible isolate. PATIENTS AND
      METHODS: This was a prospective cohort study of clinical outcome. We enrolled 497
      women (>or=18-70 years) presenting to general practitioner surgeries in Norwich
      and Gloucester with at least two symptoms of acute (<7 days) uncomplicated UTI.
      Significant bacteriuria was defined as >or=10(4) cfu/mL from a mid-stream urine
      (MSU). RESULTS: Of enrolled patients 75% (334/448) had significant bacteriuria,
      and trimethoprim resistance was present in 13.9% (44/317) of isolates. Patients
      with resistant isolates had a longer median time to symptom resolution (7 versus
      4 days, P=0.0002), greater reconsultation to the practice (39% versus 6% in first
      week, P<0.0001), more subsequent antibiotics (36% versus 4% in first week,
      P<0.0001) and higher rates of significant bacteriuria at 1 month (42% versus 20%
      with susceptible isolate, P=0.04). Half of patients reconsulting in the first
      week had a resistant organism. CONCLUSIONS: Patients with uncomplicated UTI
      caused by trimethoprim-resistant organisms had significantly worse clinical
      outcomes than those with trimethoprim-susceptible organisms. Nevertheless,
      trimethoprim resistance was rarer than predicted from routine laboratory
      submissions and we calculate that 23 women require microbiological investigation
      to prevent one reconsultation arising from resistance-based treatment failure. We
      therefore suggest empirical antibiotic treatment in acute, uncomplicated UTIs. If
      patients reconsult in the first week, we suggest a change of antibiotic treatment
      with urine culture and susceptibility testing then done. More generally,
      laboratory resources should concentrate on resistance surveillance to inform
      empirical antibiotic choice.

PMID- 16998208
TI  - Improving empirical antibiotic treatment using TREAT, a computerized decision
      support system: cluster randomized trial.
AB  - BACKGROUND: Appropriate antibiotic treatment decreases mortality, while
      superfluous treatment is associated with antibiotic resistance. We built a
      computerized decision support system for antibiotic treatment (TREAT) targeting
      these outcomes. METHODS: Prospective cohort study comparing TREAT's advice to
      physician's treatment followed by a cluster randomized trial comparing wards
      using TREAT (intervention) versus antibiotic monitoring without TREAT (control).
      We included patients suspected of harbouring bacterial infections in three
      hospitals (Israel, Germany and Italy). The primary outcome, appropriate
      antibiotic treatment, was assessed among patients with microbiologically
      documented infections (MDI). Length of hospital stay, adverse events, mortality
      (interventional trial) and antibiotic costs (both studies), including costs
      related to future antibiotic resistance, were compared among all included
      patients. RESULTS: Among 1203 patients included in the cohort study (350 with
      MDI), TREAT prescribed appropriate empirical antibiotic treatment significantly
      more frequently than physicians (70% versus 57%, P < 0.001) using less broad
      spectrum antibiotics at half physicians' antibiotic costs. The randomized trial
      included 2326 patients, 570 with MDI. The rate of appropriate empirical
      antibiotic treatment was higher in intervention versus control wards [73% versus
      64%, odds ratio (OR): 1.48, 95% confidence interval (CI): 0.95-2.29, intention to
      treat, adjusted for location and clustering]. For patients treated according to
      TREAT's advice in intervention wards, the difference with controls was highly
      significant (OR: 3.40, 95% CI: 2.25-5.14). Length of hospital stay, costs related
      to future resistance and total antibiotic costs were lower in intervention versus
      control wards. CONCLUSIONS: TREAT improved the rate of appropriate empirical
      antibiotic treatment while reducing antibiotic costs and the use of broad
      spectrum antibiotic treatment.

PMID- 16998211
TI  - Cardiopulmonary resuscitation: charting a course for the future.

PMID- 16998210
TI  - A simple clinical score for estimating the long-term risk of fracture in post
      menopausal women.
AB  - BACKGROUND: Simple tools are needed to identify patients at high risk of
      fracture. AIM: To develop a simple clinical tool for assessing 5-year risk of
      fracture. DESIGN: Cohort study. METHODS: The study population consisted of all
      women aged 50+ included in the THIN Research Database (containing computerized
      medical records of UK general practices). Using Cox proportional hazards models,
      a risk score was initially estimated from age, body mass index, and clinical risk
      factors. The 5-year risk of fracture (survival function) was estimated for each
      score. RESULTS: The study population included 366 104 women aged > or = 50 years
      (mean follow-up 5.8 years). Of these, 6453 suffered a hip fracture. Several
      characteristics independently contributed to the fracture risk score (age, body
      mass index, fracture and fall history, previous diagnoses and use of medication).
      The 5-year risks for hip fracture for patients with total scores of 10, 30 and 50
      were 0.3% (95%CI 0.3-0.4%), 2.2% (95%CI 2.1-2.2%), and 13.1% (95%CI 12.5-13.7%),
      respectively. A woman aged 65 years with low BMI and a history of both fracture
      and falling would have a hip fracture risk score of 37, with a corresponding 5
      year risk for a hip fracture of 4.1% (4.0-4.2%). The risk score was validated and
      tested in another population (from GPRD), with a good concurrence between
      predicted and observed risks of fracture. DISCUSSION: This risk score predicts
      the long-term risk of fracture, and could be used for targeting patients for
      further investigation, such as bone densitometry.

PMID- 16998213
TI  - Elevated plasma asymmetric dimethyl-L-arginine in a patient with Gordon syndrome.

PMID- 16998212
TI  - Soy protein diet improves endothelial dysfunction in renal transplant patients.
AB  - BACKGROUND: Since it has been demonstrated that soy diet can improve endothelial
      function, in the present study we evaluated the effect of dietary substitution of
      25 g of animal proteins with soy proteins on endothelial dysfunction in renal
      transplant patients. METHODS: In 20 renal transplant patients (55 +/- 11 years,
      serum creatinine 1.7 +/- 0.6 mg/dl), brachial artery flow mediated dilation (FMD)
      and endothelium-independent vasodilation (sublingual nitroglycerine, 25 microg)
      were measured at baseline, after 5 weeks of a soy diet and finally after 5 weeks
      of soy wash-out. Changes in plasma lipids, markers of oxidative stress (lipid
      peroxides, LOOH) and inflammation (C-reactive protein), isoflavones (genistein
      and daidzein), asymmetric dimethyl arginine (ADMA) and L-arginine were also
      evaluated. RESULTS: At baseline, patients showed a significantly lower FMD as
      compared with age-matched healthy subjects (3.2 +/- 1.8 vs 6.3 +/- 1.9,
      respectively; P < 0.001), while response to nitroglycerine was similar. After soy
      diet, actual protein intake was not changed, cholesterol and lipid peroxides were
      significantly reduced, and isoflavones were detectable in plasma. Soy diet was
      associated with a significant improvement in FMD (4.4 +/- 2.0; P = 0.003 vs
      baseline), while response to nitroglycerine was unchanged. Improvement in FMD was
      related to L-arginine/ADMA ratio changes, but no significant relation was found
      to changes in cholesterol, lipid peroxides or genistein and daidzein plasma
      concentrations. After 5 weeks of soy diet discontinuation, FMD (3.3 +/- 1.7%)
      returned to baseline values and isoflavones were no longer detectable in plasma.
      CONCLUSIONS: A soy protein diet for 5 weeks improves endothelial function in
      renal transplant patients. This effect seems to be strictly dependent on soy
      intake as it disappears after soy withdrawal and is mediated by an increase in
      the L-arginine/ADMA ratio, independently of change in lipid profile, oxidative
      stress or isoflavones.

PMID- 16998214
TI  - Effect of statin treatment on renal function and serum uric acid levels and their
      relation to vascular events in patients with coronary heart disease and metabolic
      syndrome: a subgroup analysis of the GREek Atorvastatin and Coronary heart
      disease Evaluation (GREACE) Study.
AB  - BACKGROUND: Metabolic syndrome (MetS) is associated with increased risk for both
      vascular and chronic kidney disease. Whether statins ameliorate these risks is
      not established. METHODS: This post hoc analysis of the GREek Atorvastatin and
      Coronary heart disease (CHD). Evaluation (GREACE) examines the effect of statins
      on estimated glomerular filtration rate (e-GFR) and serum uric acid (SUA) levels
      and their relation to vascular events in CHD patients with MetS. MetS patients
      were divided into two groups: Group A (n = 365) received lifestyle advice, target
      driven treatment with statins (mainly atorvastatin) and treatment for
      hypertension and elevated glucose. Group B (n = 347) received the same except for
      statins. Patients without MetS were divided into those who received treatment
      similar to Group A and Group B [Groups C (n = 504) and D (n = 384),
      respectively]. All patients were followed for 3 years. RESULTS: A total of 12.1%
      of patients in Group A experienced a vascular event vs 28% in Group B; risk ratio
      (RR) 0.43, 95% confidence interval (CI) 0.20-0.64, P < 0.0001, while in those
      without MetS (Group C vs Group D), the respective RR was 0.59, 95% CI 0.41-0.79,
      P < 0.0001. In Group A, e-GFR increased by 13.7% and SUA levels fell by 8.9%,
      while in Group B e-GFR was reduced by 5.8% and SUA increased by 4.3% (P < 0.005).
      Stepwise regression analysis showed that these changes were independently related
      to vascular events. CONCLUSION: Among CHD patients, those with MetS benefited
      more from statin treatment than those without MetS. This benefit could be
      partially attributed to favourable changes in e-GFR and SUA levels probably
      induced by statin treatment.

PMID- 16998215
TI  - Urinary biochemistry in experimental septic acute renal failure.
AB  - BACKGROUND: Several biochemical urine tests and derived indices are reported as
      useful in the diagnosis of acute renal failure (ARF) and its classification in
      prerenal (hypoperfusion) or intrarenal (acute tubular) necrosis. However, they
      have not been adequately studied in sepsis, the most frequent cause of ARF in
      ICU. METHODS: In 10 female Merino ewes, we implanted flow probes around the
      pulmonary and renal arteries to measure cardiac output and renal blood flow (RBF)
      continuously. Cardiovascular variables were monitored and urine samples collected
      during a 48 h control period and one week later during a 48 h period of
      hyperdynamic sepsis induced by an infusion of live Escherichia coli. RESULTS:
      Infusion of live E. coli induced systemic hyperdynamic sepsis with renal
      vasodilatation and increased RBF. Serum creatinine increased from 73.3 +/- 15.1
      to 276.9 +/- 156.3 micromol/l (P < 0.05) and creatinine clearance decreased from
      84.6 +/- 21.4 to 27.5 +/- 21.4 ml/min (P < 0.05). Urine sodium concentration
      (UNa) decreased significantly from 164.5 +/- 50.4 to 14.6 +/- 14.3 mmol/l,
      fractional excretion of sodium (FeNa) from 1.5 +/- 0.17 to 0.12 +/- 0.11%,
      fractional excretion of urea nitrogen (FeUn) from 62.7 +/- 9.5 to 11.5 +/- 15.4%,
      and urine osmolality from 724.8 +/- 277.1 mosmol/l to 329.0 +/- 52.1 mosmol/l.
      The u/p creatinine ratio did not change. CONCLUSION: Sustained Gram-negative
      sepsis induced a hyperdynamic state and hyperaemic ARF. Despite increased renal
      perfusion, UNa, FeNa and FeUn decreased significantly. Our findings suggest that,
      in sepsis, these urinary biochemical changes are not reliable markers of renal
      hypoperfusion.

PMID- 16998216
TI  - Confounding effect of comorbidity in survival studies in patients on renal
      replacement therapy.
AB  - BACKGROUND: After taking other confounding factors into account, the impact of
      comorbidity on mortality was investigated when comparing mortality between five
      European countries, dialysis modalities and renal disease groups. METHODS: The
      study included 15 571 incident patients on renal replacement therapy (RRT) from
      five national or regional registries participating in the European Renal
      Association-European Dialysis and Transplant Association Registry that collect
      comorbidity data. The presence of diabetes mellitus, ischaemic heart disease,
      peripheral vascular disease, cerebrovascular disease and malignancy was recorded
      at the start of RRT. RESULTS: The comorbidities were each independently
      associated with mortality, with hazard ratios (HRs) ranging from 1.40 (95% CI:
      1.30-1.51) for peripheral vascular disease to 1.65 (95% CI: 1.48-1.83) for
      diabetes. Age, gender, primary renal disease, modality and country together
      explained 14.4% of the variance in mortality; the comorbidities explained an
      additional 1.9%. In the comparison of renal vascular disease with
      glomerulonephritis, the crude HR of 2.40 (95% CI: 2.12-2.72) changed to 1.24 (95%
      CI: 1.09-1.41) after adjustment for age, gender, primary renal disease, treatment
      modality and country and to 1.06 (95% CI: 0.93-1.22) after further adjustment for
      the comorbidities. For the comparison between countries and other patient groups,
      the change in the survival estimate after adjustment for comorbidity was less.
      CONCLUSION: Comorbidity is an important predictor for mortality. However, after
      adjustment for age, gender, primary renal disease, treatment modality and
      country, when comparing outcomes between patient groups the influence of
      comorbidity may be less important than expected.

PMID- 16998217
TI  - Differential regulation of L-arginine transporters (cationic amino acid
      transporter-1 and -2) by peroxynitrite in rat mesangial cells.
AB  - BACKGROUND: It has become evident that increased nitric oxide (NO) generation may
      be associated with production of reactive oxygen species, such as peroxynitrite
      (ONOO-). Peroxynitrite has been postulated to be responsible for several of the
      cytotoxic effects previously ascribed to NO. Since cellular arginine uptake has
      been shown to modulate nitric oxide synthase activity, we were intrigued to study
      the effect of ONOO- on arginine traffic in renal mesangial cells. METHODS:
      Arginine uptake, CAT-1 and CAT-2 mRNA expression by northern blotting analysis,
      and CAT-1 protein content using western blotting were determined in mesangial
      cells pre-treated with peroxynitrite (0.1 and 0.5 mM) for 2 h. RESULTS:
      Peroxynitrite induced a significant increase in arginine uptake and CAT-2 mRNA
      expression compared with untreated cells. In contrast, CAT-1 mRNA expression and
      protein abundance were diminished. CONCLUSIONS: In rat mesangial cells,
      peroxynitrite augments arginine uptake via augmentation of CAT-2 while decreasing
      CAT-1 expression.

PMID- 16998218
TI  - Associations of race with depression and symptoms in patients on maintenance
      haemodialysis.
AB  - BACKGROUND: Although studies have shown that African American haemodialysis
      patients report better overall quality of life than Whites, racial differences in
      depression and symptom burden remain less well characterized. The aim of this
      study was to compare these domains between African American and White patients on
      chronic haemodialysis. METHODS: We surveyed African American and White
      maintenance haemodialysis patients. Depression was assessed using the Beck
      Depression Inventory (BDI) and Cognitive Depression Index (CDI). Symptoms were
      evaluated using the Dialysis Symptom Index (DSI). RESULTS: Among the 82 Whites
      and 78 African Americans enrolled, there were no racial differences in the
      prevalence of depression (27% in African Americans vs 27% in Whites, P = 1.0),
      BDI Scores (11.2 vs 10.9, P = 0.6) or CDI scores (6.0 vs 6.0, P = 0.9). Symptom
      burden was substantial in both African Americans and Whites (median number of
      symptoms 8.5 and 9.0, respectively) with no racial differences in the overall
      burden or severity of symptoms. However, based on a single item, African
      Americans were more likely to describe their religious/spiritual beliefs as "very
      important". Adjustment for demographic and treatment characteristics had no
      impact on the associations of race with depression or symptoms. CONCLUSIONS:
      Depression and symptoms are highly prevalent in both African American and White
      haemodialysis patients, without racial differences in these health-related
      domains. In exploratory analyses, spiritual/religious beliefs appear to be of
      greater importance to African Americans. The relevance of these observations to
      the advantages in quality of life and survival among African Americans on
      haemodialysis warrants further investigation.

PMID- 16998219
TI  - Current recommendations for diagnosis and management of polyoma BK virus
      nephropathy in renal transplant recipients.

PMID- 16998220
TI  - Pyrrolidine dithiocarbamate exerts anti-proliferative and pro-apoptotic effects
      in renal cell carcinoma cell lines.
AB  - BACKGROUND: The activation of nuclear factor-kappaB (NF-kappaB) has been
      implicated in the development, progression and metastasis of renal cell carcinoma
      (RCC). This study investigates the effect of pyrrolidine dithiocarbamate (PDTC),
      a NF-kappaB inhibitor, on two metastatic human RCC cell lines, ACHN and SN12K1.
      METHODS: RCC cell lines and normal cells were exposed to 25 or 50 microM of PDTC.
      Apoptosis was measured by flow cytometry and TdT-mediated nick end labelling
      methods. Cell viability and proliferation were measured by MTT and BrdU assays,
      respectively. Expression of NF-kappaB subunits, IkappaBs, IkappaB Kinase (IKK)
      complex and apoptotic regulatory proteins were analysed by western blotting
      and/or immunofluorescence. DNA-binding activity of NF-kappaB subunits were
      measured by ELISA. RESULTS: RCC cell lines had a higher basal level expression of
      all the five subunits of NF-kappaB than normal primary cultures of human proximal
      tubular epithelial cells or HK-2 cells. PDTC decreased the viability and
      proliferation of RCC, but not normal cells. Of the two RCC cell lines, ACHN had a
      higher basal level expression of all the five NF-kappaB subunits than SN12K1 and
      was more resistant to PDTC. While PDTC induced an overall decrease in expression
      of all the five NF-kappaB subunits in both RCC cell lines, unexpectedly, it
      increased the nuclear expression of NF-kappaB in ACHN, but not in SN12K1. PDTC
      reduced the DNA-binding activity of all the NF-kappaB subunits and the expression
      of the IKK complex (IKK-alpha, IKK-beta and IKK-gamma) and the inhibitory units
      IkappaB-alpha and IkappaB-beta. PDTC induced a significant increase in apoptosis
      in both RCC cell lines. This was associated with a decrease in expression of the
      anti-apoptotic proteins, Bcl-2 and Bcl-(XL), without marked changes in the pro
      apoptotic protein Bax. CONCLUSION: These data suggest that PDTC has the potential
      to be an anticancer agent in some forms of RCC.

PMID- 16998221
TI  - Amyloidosis-related nephrotic syndrome due to a G654A gelsolin mutation: the
      first report from the Middle East.

PMID- 16998222
TI  - Elevated levels of C-reactive protein independently predict accelerated
      deterioration of graft function in renal transplant recipients.
AB  - BACKGROUND: Chronic transplant dysfunction is characterized by a gradual decline
      in renal function with slowly rising serum creatinine. The underlying mechanism
      is thought to include inflammation and atherosclerosis. C-reactive protein (CRP)
      is a well-established marker of both inflammation and atherosclerosis. In this
      prospective study, we investigated whether CRP could be of use as a clinical
      marker for early identification of renal transplant recipients at increased risk
      of deterioration of graft function. METHODS: In this prospective study, all
      participating patients (n = 606) visited the out-patient clinic at least once a
      year, and serum creatinine was assessed at every visit. Subjects with a follow-up
      of <1 year (n = 31) were excluded from analysis. RESULTS: A total of 575 patients
      participated at a median (interquartile range) time of 5.9 (2.6-11.3) years post
      transplantation. Median time of follow-up was 3.0 (2.4-3.4) years. Changes in
      serum creatinine during follow-up were -0.45 (-4.83-4.76) micromol/l/year in 172
      subjects with CRP <1.0 mg/l, 1.04 (-3.36-6.12) micromol/l/year in 184 subjects
      with CRP 1.0-3.0 mg/l and 2.34 (-3.33-9.07) micromol/l/year in 219 subjects with
      CRP >3.0 mg/l (P < 0.05 for comparison of the three groups). Proteinuria (P =
      0.003), CMV IgG titre (P = 0.01), donor age (P = 0.01), CRP concentration (P =
      0.02), recipient age (P = 0.02) and recipient gender (P = 0.047) were
      independently associated with change in serum creatinine during follow-up in a
      multivariate analysis. CONCLUSIONS: Elevated levels of CRP independently predict
      accelerated deterioration of graft function in renal transplant recipients >1
      year post-transplantation. Further prospective studies are required to
      investigate whether early intervention can prevent deterioration of graft
      function in subjects with elevated levels of CRP.

PMID- 16998223
TI  - The effect of intrauterine growth retardation on renal function in the first two
      months of life.
AB  - BACKGROUND: Children born with growth retardation (GR) have a smaller nephron
      number and are at increased risk for the development of renal disease and
      hypertension in adult life. Data on the immediate post-natal development of renal
      function in neonates born with GR are limited and data on the effects of
      aminoglycosides (AGs) on renal function in these infants are lacking. METHODS:
      This was a prospective study of 81 preterm neonates with a mean gestational age
      of 32.5 weeks, 40 born with GR (small for gestational age, SGA) and 41 without GR
      (appropriate for gestational age, AGA). The infants were classified into 4
      groups. Groups A (n = 21) and B (n = 20) consisted of AGA and SGA neonates,
      respectively, who received AGs, and groups C (n = 20) and D (n = 20) of AGA and
      SGA neonates, respectively, who did not receive AG treatment. Indices of renal
      function were: serum creatinine (SeCr), the fractional excretion of sodium
      (FENa), potassium (FEK), phosphorus (FEP), magnesium and uric acid (FEUA), the
      urinary calcium/creatinine ratio and the transtubular potassium gradient (TTKG).
      RESULTS: No differences were observed in the parameters examined between SGA and
      AGA neonates who did not receive AGs. Conversely, SGA infants who received AGs
      after birth (group B) exhibited higher values of SeCr 2 months later.
      Specifically, their mean +/- SD value of SeCr (micromol/l) was 42 +/- 05 compared
      with 33 +/- 08 in group D, 35 +/- 04 in group A and 33 +/- 04 in group C (P <
      0.01). These infants also had significantly higher values of TTKG than SGA
      infants without AG treatment (22 +/- 9 vs 13 +/- 3 in group D) and FEUA (60 +/-
      23 vs 35 +/- 14 in group D). Their FENa and FEP were also inappropriately high
      despite having lower serum levels of Na and P. CONCLUSION: Preterm SGA infants
      who had no need of AG treatment after birth have similar renal functional
      maturation than AGA preterm infants at 2 months of life, but preterm SGA infants
      who received AGs had indications of impaired glomerular and tubular function at
      this age.

PMID- 16998224
TI  - Exit site infection due to Zygomycosis resulting in abdominal wall necrosis in a
      continuous ambulatory peritoneal dialysis patient.

PMID- 16998225
TI  - Strain susceptibility to active induction and passive transfer of experimental
      autoimmune glomerulonephritis in the rat.
AB  - BACKGROUND: Previous studies have shown that different inbred rat strains vary in
      their susceptibility to experimental autoimmune glomerulonephritis (EAG). The
      Wistar Kyoto (WKY) rat is highly susceptible and develops crescentic
      glomerulonephritis, while the Lewis (LEW) rat is resistant. When immunized with
      collagenase-solubilized rat glomerular basement membrane (GBM), both strains
      produce circulating autoantibodies reactive with rat GBM by enzyme-linked
      immunosorbent assay, but only the WKY rat shows strong linear deposits of IgG on
      the GBM. METHODS: We investigated the hypothesis that differences in the
      characteristics of the anti-GBM antibodies produced, or in the inflammatory
      response to antibody deposition, could account for susceptibility. RESULTS: We
      found that circulating anti-GBM antibodies from WKY rats immunized with GBM were
      present at a higher concentration than those from LEW rats. Antibodies from WKY
      rats also recognized the rat alpha3 chain of type IV collagen [alpha3(IV)NC1],
      whereas those from LEW rats did not. Antibody eluted from the kidneys of WKY rats
      with EAG induced by GBM showed a higher affinity for GBM and recombinant rat
      alpha3(IV)NC1 than circulating antibody. This eluted antibody bound strongly to
      normal kidney sections from both WKY and LEW rats. Passive transfer of eluted
      anti-GBM antibodies from WKY rats with EAG resulted in similar binding of IgG to
      the GBM of WKY and LEW rats at 24 h. However, only the WKY recipients went on to
      develop crescentic glomerulonephritis by 28 days. CONCLUSIONS: This study
      demonstrates that the characteristics of the anti-GBM antibodies induced in WKY
      rats contribute to their susceptibility to EAG. However, the passive transfer
      experiments reveal that factors related to the inflammatory response to antibody
      deposition are also important in determining susceptibility. A combination of
      these genetic influences could explain the variation in severity of human anti
      GBM disease.

PMID- 16998226
TI  - Autosomal dominant inheritance of non-syndromic renal hypoplasia and dysplasia:
      dramatic variation in clinical severity in a single kindred.

PMID- 16998227
TI  - A renal transplant recipient with multiple facial nodules.

PMID- 16998228
TI  - Nitrocompound activation by cell-free extracts of nitroreductase-proficient
      Salmonella typhimurium strains.
AB  - A characterization of nitrocompounds activation by cell-free extracts (CFE) of
      wild-type (AB(+)), SnrA deficient (B(+)), Cnr deficient (A(+)) and SnrA/Cnr
      deficient (AB(-)) Salmonella typhimurium strains has been done. The Ames
      mutagenicity test (S. typhimurium his(+) reversion assay) was used, as well as
      nitroreductase (NR) activity determinations where the decrease in absorbance
      generated by nitrofurantoin (NFN) reduction and NADP(H) oxidation in the presence
      of NFN, nitrofurazone (NFZ), metronidazole (MTZ) and 4-nitroquinoline-1-oxide
      (4NQO) were followed. Different aromatic and heterocyclic compounds were tested
      for mutagenic activation: 2-nitrofluorene (2-NF); 2,7-dinitrofluorene (2,7-DNF);
      1-nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP); 1,6-dinitropyrene (1,6-DNP);
      and 1,8-dinitropyrene (1,8-DNP). Differential mutagenicity was found with
      individual cell free extracts, being higher when the wild type or Cnr containing
      extract was used; nevertheless, depending on the nitrocompound, activation was
      found when either NR, SnrA or Cnr, were present. In addition, all nitrocompounds
      were more mutagenic after metabolic activation by CFE of NR proficient strains,
      although AB(-) extract still showed activation capacity. On the other hand, NR
      activity was predominantly catalyzed by wild type CFE followed by A(+), B(+) and
      AB(-) extracts in that order. We can conclude that results from the Ames test
      indicate that Cnr is the major NR, while NFN and NFZ reductions were
      predominantly catalyzed by SnrA. The characterization of the residual NR activity
      detected by the mutagenicity assay and the biochemical determinations in the AB(
      ) CFE needs further investigation.

PMID- 16998229
TI  - Comparative genotoxicity of the herbicides Roundup, Stomp and Reglone in plant
      and mammalian test systems.
AB  - The genotoxicities of the herbicides Roundup (glyphosate), Stomp (pendimethaline)
      and Reglone (diquat), were compared in plant (Crepis capillaris L.) and mouse
      bone marrow test systems using chromosomal aberrations and micronuclei. Roundup
      did not induce chromosomal aberrations or micronuclei in either test system.
      Reglone also did not induce chromosomal aberrations in either test system;
      however, it increased micronucleus frequency in both plant cells and mouse bone
      marrow polychromatic erythrocytes (PCEs). The responses of the two test systems
      to Stomp were quite different. Stomp did not induce chromosomal aberrations in
      the plant cells, but increased their incidence in mouse cells; Stomp increased
      the frequency of micronuclei in both test systems. The induction of micronuclei
      in plant cells may have been due to the spindle-destroying effect of the
      herbicide, since all concentrations of Stomp produced C-mitoses. The increased
      chromosomal aberration frequency in mouse bone marrow cells observed at later
      sampling times after administration of Stomp into animals suggests that the
      induction of aberrations may be due to biosynthesis of genotoxic metabolites.
      This conclusion was supported by the coincidence between the frequencies of
      chromosomal aberrations and of micronucleated PCEs in mouse cells. These data
      indicate that plant and animal assays are differentially responsive to some
      pesticides, and these differences may be due to metabolism and their responses to
      mitotic spindle disruption.

PMID- 16998230
TI  - Collection, validation and generation of bitumen fumes for inhalation studies in
      rats Part 3: Regeneration of bitumen fumes, inhalation setup, validation.
AB  - Undertaking a chronic inhalation study on bitumen fume presents a challenge in
      terms of generating sufficient amounts of representative fume. The objective of
      the study described in this and in previous publications was to collect
      sufficient fume and use this to develop a laboratory-generated exposure
      atmosphere, for use in chronic inhalation toxicity studies in rats that
      resembles, as closely as possible, personal exposures seen in workers during road
      paving operation. To achieve this goal, atmospheric workplace samples were
      collected at road paving work sites and compared with bitumen fume condensate
      samples collected from the headspace of hot bitumen storage tanks. In Parts 1 and
      2, we described the collection and analysis of workplace samples, the strategy
      for in-line extraction of a suitable fraction of bitumen fume collected from the
      headspace of a bitumen storage tank and the comparison of the collected
      condensate to the workplace samples. This paper (Part 3) describes the
      regeneration of bitumen fume for inhalation and the exposure setup used for
      inhalation studies.

PMID- 16998231
TI  - Pesticides and the residential bystander.

PMID- 16998232
TI  - Occupational hygiene education and status: global trends and a global future.

PMID- 16998233
TI  - Unstable diabetes in a patient receiving anti-TNF-alpha for rheumatoid arthritis.

PMID- 16998234
TI  - Autoimmunity vs autoinflammation in Behcet's disease: do we oversimplify a
      complex disorder?

PMID- 16998235
TI  - Mycophenolate mofetil for interstitial lung disease in scleroderma.

PMID- 16998236
TI  - FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain.
AB  - 2-Hydroxy fatty acids are relatively minor species of membrane lipids found
      almost exclusively as N-acyl chains of sphingolipids. In mammals, 2-hydroxy
      sphingolipids are uniquely abundant in myelin galactosylceramide and sulfatide.
      Despite the well-documented abundance of 2-hydroxy galactolipids in the nervous
      system, the enzymatic process of the 2-hydroxylation is not fully understood. To
      fill this gap, we have identified a human fatty acid 2-hydroxylase gene (FA2H)
      that is highly expressed in brain. In this report, we test the hypothesis that
      FA2H is the major fatty acid 2-hydroxylase in mouse brain and that free 2-hydroxy
      fatty acids are formed as precursors of myelin 2-hydroxy galactolipids. The fatty
      acid compositions of galactolipids in neonatal mouse brain gradually changed
      during the course of myelination. The relative ratio of 2-hydroxy versus
      nonhydroxy galactolipids was very low at 2 days of age ( approximately 8% of
      total galactolipids) and increased 6- to 8-fold by 30 days of age. During this
      period, free 2-hydroxy fatty acid levels in mouse brain increased 5- to 9-fold,
      and their composition was reflected in the fatty acids in galactolipids,
      consistent with a precursor-product relationship. The changes in free 2-hydroxy
      fatty acid levels coincided with fatty acid 2-hydroxylase activity and with the
      upregulation of FA2H expression. Furthermore, mouse brain fatty acid 2
      hydroxylase activity was inhibited by anti-FA2H antibodies. Together, these data
      provide evidence that FA2H is the major fatty acid 2-hydroxylase in brain and
      that 2-hydroxylation of free fatty acids is the first step in the synthesis of 2
      hydroxy galactolipids.

PMID- 16998237
TI  - Triterpenoid CDDO-Me blocks the NF-kappaB pathway by direct inhibition of IKKbeta
      on Cys-179.
AB  - The novel oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9,-dien-28-oic acid
      (CDDO) and the C-28 methyl ester (CDDO-Me) induce apoptosis of human tumor cells
      by disruption of redox balance and are currently in clinical trials. The present
      studies show that CDDO and CDDO-Me block tumor necrosis factoralpha-induced
      targeting of NF-kappaB p65 to the nucleus. CDDO-Me also blocked tumor necrosis
      factor alpha-induced phosphorylation of IkappaBalpha. In concert with these
      results, we found that CDDO-Me inhibits IkappaBalpha kinasebeta (IKKbeta)
      activity in cells. In support of a direct mechanism, CDDO-Me inhibited
      recombinant IKKbeta activity in vitro. The results also demonstrate that (i) CDDO
      and CDDO-Me form adducts with IKKbeta, but not IKKbeta with mutation of Cys-179
      to Ala, and (ii) CDDO-Me inhibits IKKbeta by a mechanism dependent on oxidation
      of Cys-179. These findings indicate that CDDO and CDDO-Me directly block IKKbeta
      activity and thereby the NF-kappaB pathway by interacting with Cys-179 in the
      IKKbeta activation loop.

PMID- 16998238
TI  - Diminished FAD binding in the Y459H and V492E Antley-Bixler syndrome mutants of
      human cytochrome P450 reductase.
AB  - Numerous mutations/polymorphisms of the POR gene, encoding NADPH:cytochrome P450
      oxidoreductase (CYPOR), have been described in patients with Antley-Bixler
      syndrome (ABS), presenting with craniofacial dysmorphogenesis, and/or disordered
      steroidogenesis, exhibiting ambiguous genitalia. CYPOR is the obligate electron
      donor to 51 microsomal cytochromes P450 that catalyze critical steroidogenic and
      xenobiotic reactions, and to two heme oxygenase isoforms, among other redox
      partners. To address the molecular basis of CYPOR dysfunction in ABS patients,
      the soluble catalytic domain of human CYPOR was bacterially expressed. WT enzyme
      was green, due to air-stable FMN semiquinone (blue) and oxidized FAD (yellow).
      The ABS mutant V492E was blue-gray. Flavin analysis indicated that WT had a
      protein:FAD:FMN ratio of approximately 1:1:1, whereas approximately 1:0.1:0.9 was
      observed for V492E, which retained 9% of the WT k(cat)/K(m) in NADPH:cytochrome c
      reductase assays. V492E was reconstituted upon addition of FAD, post
      purification, as shown by flavin analysis, activity assay, and near UV-visible
      CD. Both Y459H and V492E were expressed as membrane anchor-containing proteins,
      which also exhibited FAD deficiency. CYP4A4-catalyzed omega-hydroxylation of
      prostaglandin E1 was supported by WT CYPOR but not by either of the ABS mutants.
      Hydroxylation activity was rescued for both Y459H and V492E upon addition of FAD
      to the reaction. Based on these findings, decreased FAD-binding affinity is
      proposed as the basis of the observed loss of CYPOR function in the Y459H and
      V492E POR mutations in ABS.

PMID- 16998240
TI  - Interventional endosonography for pancreatic cancer.

PMID- 16998239
TI  - The transition between the B and Z conformations of DNA investigated by targeted
      molecular dynamics simulations with explicit solvation.
AB  - The transition between the B and Z conformations of double-helical
      deoxyribonucleic acid (DNA) belongs to the most complex and elusive
      conformational changes occurring in biomolecules. Since the accidental discovery
      of the left-handed Z-DNA form in the late 1970s, research on this DNA morphology
      has been engaged in resolving questions relative to its stability, occurrence,
      and function in biological processes. While the occurrence of Z-DNA in vivo is
      now widely recognized and the major factors influencing its thermodynamical
      stability are largely understood, the intricate conformational changes that take
      place during the B-to-Z transition are still unknown at the atomic level. In this
      article, we report simulations of this transition for the 3'-(CGCGCG)-5' hexamer
      duplex using targeted molecular dynamics with the GROMOS96 force field in
      explicit water under different ionic-strength conditions. The results suggest
      that for this oligomer length and sequence, the transition mechanism involves:
      1), a stretched intermediate conformation, which provides a simple solution to
      the important sterical constraints involved in this transition; 2), the transient
      disruption of Watson-Crick hydrogen-bond pairing, partly compensated
      energetically by an increase in the number of solute-solvent hydrogen bonds; and
      3), an asynchronous flipping of the bases compatible with a zipperlike
      progression mechanism.

PMID- 16998241
TI  - The outcome of a long-term follow-up of pancreatic function after recovery from
      acute pancreatitis.
AB  - CONTEXT: It is generally assumed that pancreatic function recovers completely
      after mild but not after severe acute pancreatitis. OBJECTIVE: To evaluate both
      pancreatic function and quality of life in patients who had recovered from acute
      pancreatitis in a long-term follow-up study. PARTICIPANTS: Thirty-four patients
      (mean age: 56 years) who had recovered from biliary (n=26) or post ERCP (n=8)
      acute pancreatitis. The mean time after the event was 4.6 years. MAIN OUTCOME
      MEASURES: Pancreatic function was evaluated by fecal fat excretion, urinary 4
      aminobenzoic acid (PABA) recovery, oral glucose tolerance test and pancreatic
      polypeptide (PP) secretion. In addition, the quality of life was measured by the
      gastrointestinal quality of life index (GIQLI). RESULTS: Of the 34 patients, 22
      (65%) had mild and 12 (35%) had severe acute pancreatitis. Exocrine insufficiency
      (fecal fat greater than 7 g/24h and/or urinary PABA recovery less than 50%) was
      present in 22 (65%) patients: in 10 (83%) after severe and in 12 (55%) after mild
      acute pancreatitis, respectively (P=0.140). Endocrine insufficiency was present
      in 12 patients (35%): 7 (32%) mild versus 5 (42%) severe acute pancreatitis;
      P=0.711. the quality of life was significantly impaired after acute pancreatitis,
      (P=0.024). No significant relationship was found between the severity of the
      pancreatitis and impairment of the quality of life (P=0.604). CONCLUSION: In a
      significant proportion of patients who had recovered from acute pancreatitis,
      exocrine and endocrine functional impairment was found. This finding is not
      confined only to patients after severe acute pancreatitis. Routine evaluation of
      pancreatic function after acute pancreatitis should be considered.

PMID- 16998242
TI  - Pro-inflammatory cytokines affect pancreatic carcinoma cell. Endothelial cell
      interactions.
AB  - OBJECTIVES: The potential role of surgery-induced pro-inflammatory cytokines on
      the development of tumor recurrence in pancreatic cancer was investigated. MAIN
      OUTCOME MEASURES: The adhesion of 3 human pancreatic carcinoma cell lines, PanC1,
      MiaPaCa and BxPC3 to monolayers of microvascular endothelial cells after pre
      incubation with 0.1 or 10 ng/mL IL-1beta, TNF-alpha or IL-6 was assessed in a
      reproducible human in vitro assay. Untreated monolayers served as controls.
      RESULTS: Pre-incubation of microvascular endothelial cells with IL-1beta or TNF
      alpha, but not IL-6, increased adhesion of all three tumor cell lines as compared
      to adhesion in the control group. Maximally stimulated adhesion for PanC1 reached
      159%, for MiaPaCa 204% and for BxPC3 155% (all vs. the control, P<0.001). Pre
      incubation of microvascular endothelial cells with IL-1beta or TNF-alpha resulted
      in a significant up-regulation of E-selectin, ICAM-1 and VCAM-1 expression. The
      addition of anti-E-selectin, anti-ICAM-1 or anti-VCAM-1 monoclonal antibodies did
      not decrease adhesion to microvascular endothelial cells pre-incubated with IL
      1beta. Therefore, enhanced tumor cell binding seems to be independent of these
      adhesion molecules. CONCLUSIONS: Pro-inflammatory cytokines derived from surgical
      trauma may enhance tumor cell adhesion to microvascular endothelial cells and
      thus bring about more successful tumor cell implantation resulting in an
      increased risk of metastasis formation.

PMID- 16998243
TI  - Characterization of malignant pancreatic cystic lesions in the background of
      chronic pancreatitis.
AB  - CONTEXT: Cystic lesions of the pancreas in association with chronic pancreatitis
      are a diagnostic and therapeutic challenge. OBJECTIVE: The aim of the study was
      to study clinical and radiological features that may differentiate between benign
      and malignant cystic lesions of the pancreas and examine the indications for
      surgery in these patients. DESIGN: Retrospective case note study. PATIENTS:
      Patients with concomitant cystic lesions of the pancreas and chronic pancreatitis
      stated in radiology reports between 1995 and 2005. RESULTS: Thirty-one patients
      were identified with alcohol-related chronic pancreatitis with a median age of 53
      years (range: 27-82 years). Eight patients (26%) had deranged liver function
      tests and four (13%) presented a raised CA 19.9. Radiological features of cystic
      lesions of the pancreas included median cyst size of 3 cm (range: 0.8-10 cm),
      solitary cyst in 28 patients (90%) and multi-loculated in 3 patients (10%).
      Dilatation of the main pancreatic duct was seen in seven cases (23%). Overall, 12
      patients (39%) underwent surgery, 13 patients (42%) were managed with
      radiological follow-up, five patients (16%) were managed conservatively and one
      patient (3%) was treated with chemotherapy for advanced malignancy. Overall,
      three cases (10%) of this series had malignant cystic lesions of the pancreas.
      Malignant cystic lesions of the pancreas are associated with deranged liver
      function tests, elevated CA 19.9, and are larger solitary cysts on imaging.
      CONCLUSION: The differentiation between benign and malignant cystic lesions of
      the pancreas remains a diagnostic challenge, although malignant cysts tend to be
      solitary and larger. The high prevalence of malignancy merits an aggressive
      approach to follow-up and early surgical intervention.

PMID- 16998244
TI  - Pancreatic carcinoma recurrence in the remnant pancreas after a
      pancreaticoduodenectomy.
AB  - CONTEXT: We report a rare case of a repeated pancreatic resection in the remnant
      distal pancreas 18 months after a Whipple R0 procedure. CASE REPORT: In September
      2003, a 63-year-old man underwent a Whipple procedure with an extended
      lymphadenectomy, portal vein resection and direct reconstruction for pancreatic
      cancer. In September 2004, the tumor marker level increased and MR revealed a
      tumor in the remnant pancreas. There were no findings of invasion into the
      surrounding tissue or distant metastasis. After three months of systemic
      chemotherapy and a radiological reevaluation (PET and CT) in March 2005, we
      removed the remnant pancreas. Histopathologically, the tumor was classified as a
      ductal adenocarcinoma like the tumor which had been removed during the first
      operation, with infiltration of peripancreatic adipose tissue and a segmentary
      tract of the transverse mesocolon, without lymph node metastasis. CONCLUSIONS:
      There are very few reports of pancreatic carcinoma recurrence in the remnant
      pancreas after a pancreaticoduodenectomy in the literature. In most of these
      cases, it is difficult to assess whether the remnant pancreatic cancer is a
      recurrence or a second primary cancer. In our patient, the first hypothesis seems
      to be more realistic due to the brief recurrence-free survival period. Otherwise
      the high rate of multicentricity in pancreatic cancer may also explain the
      development of a secondary cancer in the remnant pancreas, even though the
      interval was relatively brief.

PMID- 16998245
TI  - Autoimmune pancreatitis diagnosed on the basis of immunohistology alone. A case
      report.
AB  - CONTEXT: The differential diagnosis between autoimmune pancreatitis and
      pancreatic cancer is sometimes difficult, especially for those patients in whom
      laboratory and radiological criteria are lacking. CASE REPORT: A 72-year-old
      woman was found to have a tumor in the head of the pancreas. Laboratory data
      showed no abnormal values, including gammaglobulins or autoantibodies. Endoscopic
      retrograde cholangiopancreatography showed extrinsic stenosis of the main
      pancreatic and lower common bile ducts. Computed tomography showed a lesion in
      the head of the pancreas. With a tentative diagnosis of head of the pancreas
      cancer, the patient underwent pancreaticoduodenectomy. Macroscopically, a tumor 2
      cm in diameter not having clear margins was evident in the head of the pancreas.
      Histological examination showed the infiltration of lymphocytes, plasma cells,
      and eosinophils with lymphoid follicles around the main pancreatic duct.
      Immunohistological examination demonstrated that the main pancreatic duct was
      surrounded by abundant IgG4-positive plasma cells. CONCLUSIONS: The patient was
      diagnosed as having autoimmune pancreatitis on the basis of the
      immunohistological findings alone, without any well-defined criteria such as high
      serum level of IgG4 and presence of autoantibodies before or after surgery.

PMID- 16998246
TI  - Acute pancreatitis in association with Campylobacter jejuni-associated diarrhea
      in a 15-year-old with CFTR mutations: is there a link?
AB  - CONTEXT: Acute pancreatitis has occasionally been reported in association with
      Campylobacter jejuni infection in humans. However, the mechanism linking
      Campylobacter jejuni infection and pancreatitis is unclear. Acute pancreatitis in
      association with an infectious illness may be related to underlying genetic
      mutations. For instance, studies show that mutations in the cystic fibrosis
      transmembrane conductance regulator gene increase the susceptibility for acute
      and chronic pancreatitis. CASE REPORT: We describe a patient with Campylobacter
      jejuni infection who developed acute pancreatitis in the setting of an underlying
      cystic fibrosis transmembrane conductance regulator gene mutation. DISCUSSION: In
      this patient with an underlying mutation in the CFTR gene, we propose that the
      interaction between the mutant gene and an environmental factor, Campylobacter
      jejuni infection, resulted in pancreatitis.

PMID- 16998247
TI  - Long-term survival in metastatic pancreatic cancer. A case report and review of
      the literature.
AB  - CONTEXT: Pancreatic cancer still remains an incurable disease. The survival rate
      of patients in all stages of the disease is poor. Overall median survival is 3-5
      months with a 12-month survival rate of 10% and a 5-year survival rate less than
      5%. CASE REPORT: We report a rare case of a long-term survivor (more than 10
      years) of metastatic carcinoma of the pancreas tail controlled with subsequent
      surgical and chemotherapeutic strategies with an acceptable performance status
      and quality of life. DISCUSSION: This is the fifth case reported in the
      literature showing that long-term survival may be achieved even in advanced
      pancreatic cancer.

PMID- 16998248
TI  - Retroperitoneal enteric duplication cyst presenting as a pancreatic cystic
      lesion. A case report.
AB  - CONTEXT: Retroperitoneal enteric duplication cysts (EDC) are rare lesions and its
      presentation during adulthood is a diagnostic challenge for clinicians. The
      diagnosis of this condition is established following histopathological analysis,
      which often requires surgical intervention. CASE REPORT: We report a case of a
      retroperitoneal enteric duplication cysts, presenting as a cystic lesion of the
      pancreas in a 19-year-old woman. CONCLUSIONS: We recommend surgical intervention
      for retroperitoneal EDCs due to its potential local complications including
      pressure effects on surrounding structures and neoplastic change.

PMID- 16998249
TI  - Pediatric pancreatic hemangioma: a case report and literature review.
AB  - CONTEXT: The pancreas is an unusual site for a hemangioma in an infant. A child
      with obstructive jaundice caused by a pancreatic hemangioma is presented and
      management strategies for this benign tumor are discussed. CASE REPORT: A 5-month
      old girl presented with a 2-week history of jaundice, pale stools and dark urine.
      Liver function tests confirmed obstructive jaundice. An abdominal ultrasound scan
      and magnetic resonance imaging showed an enhancing mass in the head of the
      pancreas. At laparotomy, a wedge biopsy of the pancreatic tumor was taken and a
      tube cholecystostomy inserted. Histological examination of the specimen revealed
      a pancreatic hemangioma with sclerotic features. The high volume of bile loss
      from the cholecystostomy proved problematic and biliary diversion with a Roux-en
      y hepaticojejunostomy was therefore performed. The tumor subsequently regressed
      spontaneously and was no longer visible on follow-up imaging two years later. The
      child has since thrived. CONCLUSIONS: Pancreatic hemangiomas are rare and may
      cause diagnostic confusion. Pancreatic resection should be avoided since the
      natural history of these benign tumors is that of spontaneous involution. Various
      strategies can be used to manage any associated obstructive jaundice.

PMID- 16998250
TI  - Issues in management of pancreatic pseudocysts.
AB  - Pancreatic pseudocysts (PPs) comprise more than 80% of the cystic lesions of the
      pancreas and cause complications in 7-25% of patients with pancreatitis or
      pancreatic trauma. The first step in the management of PPs is to exclude a cystic
      tumor. A history of pancreatitis, no septation, solid components or mural
      calcification on CT scan and high amylase content at aspiration favor a diagnosis
      of PP. Endoscopic ultrasound (EUS)-guided FNAC is a valuable diagnostic aid.
      Intervention is indicated for PPs which are symptomatic, in a phase of growth,
      complicated (infected, hemorrhage, biliary or bowel obstruction) or in those
      occurring together with chronic pancreatitis and when malignancy cannot be
      unequivocally excluded. The current options include percutaneous catheter
      drainage, endoscopy and surgery. The choice depends on the mode of presentation,
      the cystic morphology and available technical expertise. Percutaneous catheter
      drainage is recommended as a temporizing measure in poor surgical candidates with
      immature, complicated or infected PPs. The limitations include secondary
      infection and pancreatic fistula in 10-20% of patients which increase
      complications following eventual definitive surgery. Endoscopic therapy for PPs
      including cystic-enteric drainage (and transpapillary drainage), is an option for
      PPs which bulge into the enteric lumen which have a wall thickness of less than 1
      cm and the absence of major vascular structures on EUS in the proposed tract or
      those which communicate with the pancreatic duct above a stricture. Surgical
      internal drainage remains the gold standard and is the procedure of choice for
      cysts which are symptomatic or complicated or those having a mature wall,. Being
      more versatile, a cystojejunostomy is preferred for giant pseudocysts (>15 cm)
      which are predominantly inframesocolic or are in an unusual location. In PPs with
      coexisting chronic pancreatitis and a dilated pancreatic duct, duct drainage
      procedures (such as longitudinal pancreaticojejunostomy) should be preferred to a
      cyst drainage procedure.

PMID- 16998251
TI  - Pancreatic ductal carcinoma: from the bench to the bedside.

PMID- 16998252
TI  - Pulse wave analysis and pulse wave velocity: a review of blood pressure
      interpretation 100 years after Korotkov.
AB  - The pulsatile component of blood pressure (ie, pulse pressure) has received
      considerable attention as an important risk factor for cardiovascular disease. In
      particular, central blood pressure measurements in the ascending aorta or in the
      carotid artery are expected to be more useful than conventional brachial pressure
      measurements for predicting cardiovascular events because central pressure, not
      the brachial pressure, is the pressure that target organs encounter. Due to wave
      reflection, the blood pressure in the upper limb does not represent the central
      blood pressure; therefore, leading researchers have enthusiastically promoted a
      noninvasive method of measuring central blood pressure and the resulting aortic
      stiffness. Until now, there has been an increasing body of evidence to support
      the accuracy and superiority of central blood pressure measurements as well as
      the assessment of aortic properties over classical brachial pressure
      measurements. In this review, the information regarding these "central" indices
      derived from 2 main methods, namely "pulse wave analysis" and "pulse wave
      velocity", for the application of central blood pressure measurements and
      arterial stiffness to clinical study and practice, has been summarized.

PMID- 16998253
TI  - Identification of genetic factors and development of genetic risk diagnosis
      systems for cardiovascular diseases and stroke.
AB  - BACKGROUND: Polymorphisms of GJA4 and CYBA and of PAI1 and MMP3 are associated
      with myocardial infarction (MI) in men and women, respectively. In addition,
      several polymorphisms associated with restenosis after percutaneous coronary
      intervention, coronary artery spasm, or hypertension have been identified. More
      recently, a large genetic epidemiological study was performed to identify
      additional gene polymorphisms that confer susceptibility to cardiovascular
      diseases, stroke, and other complex diseases. METHODS AND RESULTS: The
      relationship of 202 polymorphisms in 152 candidate genes to MI, hypertension,
      ischemic or hemorrhagic stroke, metabolic syndrome, type 2 diabetes mellitus,
      obesity, or in-stent restenosis were examined in 5,000 unrelated Japanese
      individuals. Of these, 14 polymorphisms related to MI, 8 to atherothrombotic
      cerebral infarction, 9 to intracerebral hemorrhage, and 10 to subarachnoid
      hemorrhage were identified. This information was then used to develop risk
      diagnosis systems to predict the future risk for development of each disease in a
      given individual. CONCLUSIONS: Identification of gene polymorphisms that confer
      susceptibility to cardiovascular diseases or stroke and the development of
      genetic risk diagnosis systems may contribute to the personalized prevention of
      these conditions.

PMID- 16998254
TI  - Risk assessment chart for death from cardiovascular disease based on a 19-year
      follow-up study of a Japanese representative population.
AB  - BACKGROUND: Based on the NIPPON DATA80, risk charts for the probability of death
      from coronary heart disease (CHD), stroke, and all cardiovascular disease (CVD)
      were constructed by sex and 10-year age groups. METHODS AND RESULTS: The 9,638
      participants were followed-up for 19 years from 1980, excluding 28 individuals
      without the necessary baseline data and 257 participants with past history of
      stroke or CHD. Final analysis was performed on 9,353 participants (4,098 men,
      mean age 50.3 years; 5,255 women, mean age 50.8) using a Cox proportional hazards
      model. Death probabilities over a 10-year period from CHD, stroke, and all CVD
      were calculated and displayed as color coding on each chart by combining 10-year
      age, systolic blood pressure, smoking, and serum total cholesterol and glucose
      levels. Six different colors corresponding to probabilities of death were
      displayed on each chart. CONCLUSIONS: The original charts based on the findings
      from NIPPON DATA80 are suitable for assessing CHD, stroke, and all CVD death risk
      in the general Japanese population. These charts should be used as a health
      education tool for lifestyle modification targeting individuals with CVD risk
      factors.

PMID- 16998255
TI  - Current status of the background of patients with coronary artery disease in
      Japan.
AB  - BACKGROUND: Although the morbidity and mortality of coronary artery disease (CAD)
      vary widely with race and lifestyle, Japanese CAD patients have been clinically
      managed according to the guidelines of Western countries. To draft guidelines
      specifically for Japanese CAD patients, a database that describes how Japanese
      CAD patients are currently managed and the outcomes of those managements
      practices is required. METHODS AND RESULTS: Patients diagnosed as having 75% or
      higher stenosis according to the American Heart Association classification in at
      least 1 branch of the coronary arteries by cardiac catheterization were enrolled
      in the study. Of 15,628 patients screened from April 2000 to March 2001, 13,812
      of them met the inclusion criteria and were followed up for a mean period of 2.7
      years. The incident rate of events was 62.8 per 1,000 patients-year including all
      cause mortality of 17.5 and total cardiac events of 47.4 per 1,000 patients-year
      which is much higher than previous reports in Japan. The incident rate of acute
      myocardial infarction in this study cohort was 7.5 events per 1,000 patients
      year. CONCLUSION: The database provides a large body of information on Japanese
      CAD patients who have significant coronary atherosclerosis diagnosed by coronary
      angiography, which will be useful for planning future randomized controlled
      trials.

PMID- 16998256
TI  - Effects of alcohol consumption on cardiovascular events in male patients with
      healed myocardial infarction.
AB  - BACKGROUND: In Western countries, many studies have shown that among healthy
      people moderate drinkers have a lower incidence of cardiovascular events than
      abstainers and heavy drinkers. However, it is not clear whether this is true in
      patients with a healed myocardial infarction (MI). METHODS AND RESULTS: In the
      present study cardiovascular events were defined as cardiac events or strokes.
      Male patients only were included because the incidence of cardiovascular events
      is low in females. In patients younger than 65 years, the incidence of
      cardiovascular events was 34.6 persons per year (54 cases: 3.9%) of abstainers,
      17.4 persons per year (20 cases: 1.9%) of moderate drinkers (p<0.01 vs
      abstainers) and 30.3 s persons per year (18 cases: 3.2%) of heavy drinkers.
      However, in those aged 65 years or older, the incidence was 47.8 persons per year
      (24 cases: 4.5%) of abstainers, 58.4 persons per year (14 cases: 5.6%) of
      moderate drinkers, and 314.8 persons per year (12 cases: 19.7%) of heavy
      drinkers. In this age group, cardiovascular events were significantly higher in
      heavy drinkers than in the other 2 groups (p<0.01), and the incidence was not
      lower in the moderate drinkers than in abstainers as shown in the younger group.
      CONCLUSIONS: In patients younger than 65 years with a healed MI, drinking limited
      less than 30 ml/day (moderate intake) reduces the incidence of cardiovascular
      events, but not in those aged 65 years or older.

PMID- 16998257
TI  - Effect of combination therapy with simvastatin and carvedilol in patients with
      left ventricular dysfunction complicated with acute myocardial infarction who
      underwent percutaneous coronary intervention.
AB  - BACKGROUND: This study assessed the effects of combination therapy with
      simvastatin and carvedilol on clinical outcome in patients with left ventricular
      (LV) dysfunction after acute myocardial infarction (AMI). METHODS AND RESULTS:
      The study retrospectively analyzed the data from 672 patients with LV dysfunction
      [LV ejection fraction (LVEF) <40%] complicated with AMI who underwent
      percutaneous coronary intervention (PCI). The patients were divided into 4
      treatment groups: combination group (n=160), simvastatin only group (n=216),
      carvedilol only group (n=242), neither treatment group (n=54). At 6 months after
      PCI, the LVEF had improved most significantly in the combination group. During 1
      year follow-up, cardiac death occurred most frequently in the neither treatment
      group compared with the other 3 groups (combination: 4%, simvastatin alone: 7%,
      carvedilol alone: 8%, neither: 17%, p<0.001 between neither treatment and other 3
      groups). The results on major adverse cardiovascular events (MACE) showed that
      the combination of simvastatin and carvedilol was associated with a relative risk
      reduction of 53% (p<0.001), treatment with simvastatin alone with a relative risk
      reduction of 44% (p=0.001), and carvedilol alone with a relative risk reduction
      of 40% (p=0.003) compared with neither treatment. The independent predictors of 1
      year MACE were neither treatment, elevated high sensitivity C-reactive protein (>
      or =0.5 mg/dl), and old age (>70 years). CONCLUSION: Combination therapy with
      simvastatin and carvedilol had a positive impact on the endpoints of
      cardiovascular death and MACE and seems to have an additive beneficial effect on
      these endpoints in patients with LV dysfunction complicated with AMI who
      underwent PCI.

PMID- 16998258
TI  - Association between A/C1166 gene polymorphism of the angiotensin II type 1
      receptor and biventricular functions in patients with acute myocardial
      infarction.
AB  - BACKGROUND: Although there have been several association studies of angiotensin
      II type 1 receptor (AT1R, A/C1166) gene polymorphism in clinical endpoints such
      as myocardial infarction (MI), hypertension, aortic stiffness, and left
      ventricular mass, the relationship between AT1R polymorphism and biventricular
      function in acute anterior MI has not been studied before. METHODS AND RESULTS:
      The study group comprised 132 consecutive patients who were admitted to the
      coronary care unit with their first acute anterior MI. Systolic and diastolic
      diameters, volumes, inflow properties, ejection fraction and myocardial
      performance index of both ventricles were measured. AT1R polymorphism was
      determined using polymerase chain reaction amplification. Based on A/C1166
      polymorphism of AT1R, the patients were classified into 3 groups: group 1, A/A
      (n=91) genotype, group 2 A/C (n=28), and group 3 C/C (n=13) genotype. When the
      left ventricular and right ventricular echocardiographic functions were compared,
      all parameters of the 3 groups were found to be similar. No difference was
      detected in either the genotype distribution or allele frequencies between the
      patients and the controls for AT1R. CONCLUSIONS: The results suggest that A/C1166
      polymorphism of AT1R did not influence the risk of either acute MI or
      biventricular function after anterior MI.

PMID- 16998259
TI  - Clinical significance of aortic knob width and calcification in unstable angina.
AB  - BACKGROUND: Chest radiography is a routine examination evaluating those patients
      with chest pain. There are few data about the correlation between aortic knob
      width, calcification and coronary atherosclerosis. METHODS AND RESULTS: The
      aortic knob width was measured and the presence of aortic knob calcification was
      assessed via a chest posteroanterior view in 178 consecutive patients. The aortic
      knob width and calcification were compared to the risk factor and the extent of
      coronary artery disease. Patient's age (69.5+/-7.95 vs 61.1+/-10.29 years,
      p=0.010), the prevalence of hypertension (65.9 vs 46.3%, p=0.024) and diabetes
      (43.2 vs 26.1%, p=0.033), the level of total cholesterol (196.8+/-63.21 vs
      188.6+/-44.45 mg/dl, p=0.049) and the incidence of multi-vessel disease (65.9 vs
      38.1%, p<0.001) were higher in patients with aortic knob calcification than in
      patients without calcification. The aortic knob width and the prevalence of
      aortic knob calcification were significantly correlated with the severity of
      coronary artery disease. Multivariate analysis demonstrated that aortic knob
      calcification and diabetes were independent factors for multi-vessel disease
      (p=0.018 and p=0.012). CONCLUSIONS: The observation of aortic knob on a chest
      radiograph can provide important predictive information of coronary
      atherosclerosis.

PMID- 16998260
TI  - Effect of distal protection device on the microvascular integrity in acute
      myocardial infarction during primary percutaneous coronary intervention.
AB  - BACKGROUND: The use of a distal protection device during primary percutaneous
      coronary intervention (PCI) in acute myocardial infarction (AMI) may preserve the
      microvascular integrity of the myocardium. METHODS AND RESULTS: A total of 58
      consecutive patients with AMI, who had undergone primary PCI within 24 h after
      onset, were enrolled (30 patients with the PercuSurge GuardWire System, 28
      without). The coronary flow velocity reserve was not different between the 2
      groups. In patients with a distal protection device, the post-PCI Thrombolysis In
      Myocardial Infarction myocardial perfusion grades (TMP) were more favorable (TMP
      0/1: 13.3%, TMP 2: 23.3%, TMP 3: 63.4% vs TMP 0/1: 35.7%, TMP 2: 35.7%, TMP 3:
      28.6%, p=0.023). These patients also exhibited lower basal and hyperemic
      microvascular resistance index levels (4.33+/-2.22 vs 5.55+/-2.36 mmHg . cm(-1) .
      s, p=0.047; 2.39+/-1.40 vs 3.14+/-1.36 mmHg . cm(-1) . s, p=0.045, respectively),
      and longer basal diastolic deceleration time (679+/-273 vs 519+/-289 ms, p=0.035)
      after PCI. CONCLUSION: Distal protection with the PercuSurge GuardWire system may
      effectively preserve the microvascular integrity of the myocardium during primary
      PCI in AMI patients.

PMID- 16998261
TI  - Peak C-reactive protein concentration correlates with left ventricular thrombus
      formation diagnosed by contrast echocardiographic left ventricular opacification
      in patients with a first anterior acute myocardial infarction.
AB  - BACKGROUND: Wall motion abnormality in the apical legion of the left ventricle
      (LV) with stagnant flow alone is not sufficient to identify patients at high risk
      for LV thrombus formation among those with first anterior acute myocardial
      infarction (AMI). The aim of this study was to identify the determinants of LV
      thrombus formation using contrast echocardiography. METHODS AND RESULTS: In 75
      patients with first anterior AMI, standard and contrast echocardiography was
      performed to detect LV thrombus. Although LV thrombus was found in 10 patients
      (13%) using standard echocardiography, it was found in 15 patients (20%) using
      contrast echocardiography. Apical stagnant flow was observed in 14 patients (93%)
      with LV thrombus. In addition, patients with LV thrombus had a higher peak C
      reactive protein (CRP) concentration (18.2+/-4.3 vs 7.9+/-5.5 mg/dl, p<0.0001).
      In multivariate analysis, only peak CRP concentration was identified as an
      independent predictor of LV thrombus (p=0.02, odds ratio: 1.400, confidence
      interval: 1.040-1.884). The receiver-operating characteristics (ROC) analysis
      revealed the best cutoff value of a peak CRP concentration >10.7 mg/dl to
      identify patients with LV thrombus (sensivity 0.93, specificity 0.75, area under
      ROC curve 0.91). CONCLUSIONS: The peak CRP concentration is a useful marker of
      patients with first anterior AMI who are at high risk for LV thrombus.

PMID- 16998262
TI  - Usefulness of a novel ultrasound transducer for continuous monitoring treadmill
      exercise echocardiography to assess coronary artery disease.
AB  - BACKGROUND: The feasibility of a novel ultrasound probe, which can be attached to
      the left ventricular (LV) apex chest wall and allows free rotation around its
      long axis direction for the continuous monitoring of LV wall motion, was tested.
      METHODS AND RESULTS: There were 36 subjects who had coronary artery disease
      (CAD). By attaching a novel ultrasound probe to the chest wall, the LV apical
      views were recorded during treadmill exercise stress echocardiography (Echo). The
      continuous monitoring of LV wall motion was satisfactorily feasible in 30 of 36
      patients. The visualization rate of the overall LV segments was higher at rest
      (90%) compared to that during peak exercise (77%). The segments were better
      visualized in apical portions (90-100%) than in mid (77-96%) or basal portions
      (68-87%). The sensitivity, specificity, and accuracy for detecting CAD were 61,
      100 and 77%, respectively. The wall motion score index 3 and 6 min after exercise
      decreased significantly compared to those at peak exercise. The number of
      segments with dyssynergy was highest at the peak exercise. Ischemic ST-T
      depression on electrocardiography was observed only at peak stress periods.
      CONCLUSIONS: Continuous monitoring treadmill exercise Echo using a novel
      ultrasound probe seems feasible for the non-invasive and physiological assessment
      of CAD.

PMID- 16998263
TI  - Off-pump coronary artery bypass grafting for acute myocardial infarction.
AB  - BACKGROUND: The aim of this study was to evaluate the surgical results of off
      pump coronary artery bypass grafting (OPCAB) for patients with acute myocardial
      infarction (AMI) within 14 days of the infarction. METHODS AND RESULTS: From
      April 2000 to January 2005 among 841 patients who underwent OPCAB, 43 consecutive
      patients (5.1%) were examined. Mean age at operation was 69.5 years and mean time
      from the onset of AMI to surgery was 4.6 days. Seventeen patients (39.5%) had
      left main trunk disease. Three patients (7.0%) underwent OPCAB following
      unsuccessful percutaneous coronary intervention, and 1 patient (2.3%) underwent
      redo procedure 9 years after previous coronary artery bypass grafting (CABG). Six
      patients (14%) were admitted in cardiogenic shock. Intraaortic balloon pumping
      was inserted preoperatively in 20 patients (46.5%). The average maximum creatine
      kinase-myocardial band was 139+/-181 (U/L). The mean number of grafts was 3.2 and
      the rate of complete revascularization was 91%. Two of six patients with
      preoperative cardiogenic shock were converted to on-pump beating CABG due to
      ventricular arrythmia. The early graft patency rate was 98%. All patients
      survived except 2 with preoperative cardiogenic shock. CONCLUSIONS: OPCAB can be
      performed after AMI as a relatively low-risk procedure with an acceptable
      mortality rate, even within 14 days of the infarction.

PMID- 16998265
TI  - Three cases of iatrogenic coronary ostial stenosis after aortic valve
      replacement.
AB  - BACKGROUND: Iatrogenic coronary ostial stenosis (ICOS) is a rare but potentially
      life-threatening complication of aortic valve replacement (AVR). This
      complication is usually diagnosed by angiography and treated with aortocoronary
      bypass surgery. CASE REPORTS: In the present 3 cases pre-operative coronary
      angiography confirmed normal coronary arteries and they underwent uncomplicated
      AVR. Coronary lesions were clinically manifest within 4 months after surgery, and
      repeat coronary angiography demonstrated bilateral ostial stenosis in 1 patient
      and left main trunk stenosis in the other 2. Two cases were detected by
      multidetector computed tomography (MDCT) before angiography. MDCT and Virtual
      Histology suggested fibrous tissue formation in the lesions. All 3 patients were
      successfully underwent percutaneous coronary intervention (PCI) and stenting. The
      post-procedure clinical course has been uneventful, except for elective stenting
      of a recurrent lesion in 1 asymptomatic patient. CONCLUSIONS: The incidence of
      ICOS after AVR is low. Noninvasive MDCT is useful for early diagnosis and PCI is
      a possible alternative treatment. ICOS may be caused by fibrous tissue formation,
      and therefore be distinct from conventional atherosclerosis.

PMID- 16998264
TI  - Pharmacokinetic study and limited sampling strategy of cyclosporine in Japanese
      heart transplant recipients.
AB  - BACKGROUND: The purpose of this study was to characterize the pharmacokinetics of
      cyclosporine (CsA) in Japanese heart transplant patients, and to optimise the
      monitoring strategy based on measurements of the area under the curve of plasma
      concentration absorption phase or 2 h post-dose concentrations (C(2)). METHODS
      AND RESULTS: At defined time periods during the first year after transplantation,
      the area under the curve for the CsA serum concentration from 0 to 4 h (AUC(0-4
      h)) was evaluated. Pharmacokinetic parameters and renal function at 1 month and
      12 months after transplantation were compared in 7 Japanese patients. The highest
      coefficient of determination between CsA AUC(0-4 h) and a single concentration
      was observed using C2 (r2 =0.838). For CsA pharmacokinetics, the mean measurement
      of whole blood trough levels value at 12 months was significantly lower than at 1
      month after transplantation (p=0.026). The mean serum creatinine level at 12
      months was significantly higher than at 1 month (1.00 mg/dl vs 0.73 p=0.0194).
      CONCLUSION: A single-time-point model that includes C2 is useful for predicting
      CsA AUC(0-4 h) in Japanese heart transplant patients. Mean C2 values >1,000 ng/ml
      were obtained in patients with no rejection at 1 month and 12 months after
      transplantation; however, renal impairment may occur.

PMID- 16998266
TI  - Randomized study of angiotensin II type 1 receptor blocker vs dihydropiridine
      calcium antagonist for the treatment of paroxysmal atrial fibrillation in
      patients with hypertension.
AB  - BACKGROUND: Mega trials of rhythm vs rate control could not demonstrate the
      usefulness of available antiarrhythmic drugs, so a more effective and safer
      therapy for atrial fibrillation (AF) is now required. One candidate is the so
      called "upstream therapy", which refers to the blockade of upstream modifying
      elements (renin - angiotensin system, cathecholamines, oxidative stress etc) that
      contribute to the arrhythmogenic substrate. METHODS AND RESULTS: The Japanese
      Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is a
      randomized comparative evaluation of an angiotensin II type 1 blocker
      (candesartan) and a dihydropiridine calcium blocker (amlodipine), both combined
      with antithrombotic therapy, as an antiarrhythmic therapy for the treatment of
      paroxysmal AF (PAF) associated with hypertension. To test the usefulness of this
      therapy, this study will reveal the recurrence rate of asymptomatic as well as
      symptomatic PAF during 1-year of treatment with candesartan or amlodipine, using
      daily transtelephonic monitoring. CONCLUSIONS: The J-RHYTHM II study will follow
      400 patients with PAF and hypertension who were treated at approximately 50 sites
      throughout Japan, and will provide clinically important information.

PMID- 16998267
TI  - Characteristics of a new repolarization descriptor substituted for T-wave
      morphology analysis in patients with cardiomyopathy and myocardial infarction.
AB  - BACKGROUND: Total cosine R-to-T (TCRT) is a descriptor of T-wave morphology
      analysis based on singular value decomposition of 12-lead electrocardiograms
      (ECGs), which is useful in risk stratification of patients with myocardial
      infarction (MI). A new marker of standard ECG substituted for TCRT is proposed
      and the aim of this study was to evaluate the correlation between the new index
      and TCRT in patients with cardiomyopathy and MI. METHODS AND RESULTS: Patients
      were divided into 2 groups: patients with cardiomyopathy (group CM, n=21, male
      =13), and patients with MI (group MI, n=36, male =28). TCRT was calculated using
      a custom software package. The ventricular gradient (VG)-index was defined as the
      total number of leads with opposite vectors for the QRS and T-wave. The value of
      TCRT was significantly lower in group CM than in group MI (-0.50+/-0.51 vs 
      0.04+/-0.65, p<0.01). The value for the VG-index was significantly greater in
      group CM than in group MI (5.9+/-3.4 vs 4.2+/-2.4, p<0.05). There was a
      significant correlation between TCRT and the VG-index in all of the patients
      (r(2)=0.47). CONCLUSION: The VG-index is significantly correlated with TCRT, and
      both descriptors distinguish patients with MI from those with cardiomyopathy.

PMID- 16998268
TI  - Decrease of fractional flow reserve shortly after percutaneous coronary
      intervention.
AB  - BACKGROUND: The aim of the present study was to quantitatively assess the
      physiological acute recoil after percutaneous coronary intervention (PCI), and to
      determine the relation between it and target lesion revascularization (TLR) in
      the chronic phase. METHODS AND RESULTS: This study evaluated 76 patients who
      underwent elective PCI between May 1997 and December 2001: plain old balloon
      angioplasty (POBA) in 50 patients and bare metal stent implantation in 26
      patients. Fractional flow reserve (FFR) was measured immediately (FFR0m) and 15
      min (FFR15m) after the final dilation, and the difference (dif-FFR) was
      calculated. In POBA patients with TLR, FFR15m was significantly low (0.79+/-0.05
      vs 0.87 +/-0.08, p<0.001) and dif-FFR was significantly high (0.06+/-0.04 vs 
      0.01+/-0.04, p<0.001) compared with the patients without TLR. The patients with a
      larger dif-FFR value (> or =0.05) had a higher rate of TLR (92%). Dif-FFR was the
      strongest independent predictor of TLR. CONCLUSIONS: The changes in FFR during
      the time course shortly after coronary intervention can be detected and a
      decrease in the first 15 min after PCI is associated with a higher rate of TLR.

PMID- 16998269
TI  - Prognostic impact of ventilatory efficiency in heart disease patients with
      preserved exercise tolerance.
AB  - BACKGROUND: The minute ventilation/carbon-dioxide output (VE/VCO2) slope as a
      marker of cardiac events has been established in patients with severe heart
      failure, but it is not known whether it is useful for other heart diseases.
      METHODS AND RESULTS: The present study investigated 215 patients with various
      heart diseases (age 59+/-11 years; ischemic heart disease, n=89; dilated
      cardiomyopathy, n=38; valvular disease, n=37; hypertensive heart disease, n=33;
      others, n=18) who underwent cardiopulmonary exercise testing to determine the
      VE/VCO(2) slope. Patients were divided into 2 groups according to the VE/VCO2
      slope and were followed-up for 3 years. Forty-eight cardiac events (6 deaths, 42
      re-hospitalizations) occurred during the observation period. Patients with a
      VE/VCO2 slope >34 had a significantly higher 3-year cardiac event rate (32.1%)
      than patients with VE/VCO2 slope <34 (18.9%, p<0.05). When patients were selected
      with relatively preserved peak oxygen uptake values (>16 ml . kg (-1) . min(-1)),
      patients with VE/VCO2 slope >34 still demonstrated a significantly higher cardiac
      event rate than other patients (35.0% vs 13.3%, p<0.01). CONCLUSION: The VE/VCO2
      slope may be a prognostic indicator of cardiac events in a heterogeneous group of
      patients with heart disease, independent of exercise tolerance.

PMID- 16998270
TI  - Power spectral analysis of finger plethysmographic waveform in patients with
      coronary artery disease and after coronary artery bypass graft surgery.
AB  - BACKGROUND: The aim of the present study was to assess the clinical significance
      of spectral analysis of plethysmographic waveform in patients with coronary
      artery disease (CAD) and after coronary artery bypass graft (CABG) surgery.
      METHODS AND RESULTS: The study group comprised 26 healthy subjects, 15 CAD
      patients, and 24 CAD patients after CABG. Finger plethysmographic waveforms from
      both right and left index fingers were recorded and analyzed using power spectral
      analysis. The total power of the right pulse was found to be higher than that of
      left pulse in the 3 groups of subjects. In CABG patients, the total power of both
      pulses was increased, the right-to-left ratio of bilateral total power was
      decreased, and the power of the harmonics of the right pulse shifted from high
      frequency to low-frequency. The normalized power of the 4th harmonic of the left
      pulse and of the 3rd and 4th harmonics of right pulse decreased, whereas that of
      the 1st harmonic of right pulse increased in CABG patients. Several harmonics
      correlated significantly to some heart rate variability measures in both controls
      and CAD patients, but not in CABG patients. CONCLUSIONS: The increase in the
      total power of both pulses, the shift of the normalized power of harmonics of the
      right pulse from high- to low-frequency, and the decrease in the right-to-left
      ratio of the total power of both pulses are the 3 significant changes in the
      power spectra of the pulses in CAD patients after CABG. The plethysmographic
      waveform of normal controls and CAD patients may be modulated by the autonomic
      nervous system, and in CAD patients the CABG surgery may have diminished the
      effect of autonomic nervous modulation on the pulse waveforms.

PMID- 16998271
TI  - Role of mechanical stress in the form of cardiomyocyte death during the early
      phase of reperfusion.
AB  - BACKGROUND: The hypothesis that mechanical stress during reperfusion produces
      myocyte oncosis and inhibits apoptosis was tested in the present study. METHODS
      AND RESULTS: Isolated and perfused rat hearts were subjected to 30 min ischemia
      followed by 150 min reperfusion. In the control-reperfusion heart, the form of
      myocyte death was a mixture of apoptosis only, oncosis only, and both apoptosis
      and oncosis. Apoptotic myocytes contained mitochondria that maintained membrane
      potential (Deltapsim), whereas oncotic myocytes contained only Deltapsim
      collapsed mitochondria. Treatment with the contractile blocker 2,3-butanedione
      monoxime (BDM) during reperfusion increased caspase-3 activity and produced
      predominantly apoptosis. However, withdrawal of BDM provoked oncosis in terminal
      deoxynucleotide nick-end labeling (TUNEL)-positive myocytes. Myocardial stretch
      by inflating an intraventricular balloon at the time of reperfusion with BDM
      increased only oncotic myocytes, whereas the same mechanical stress 120 min after
      reperfusion increased oncotic myocytes positive for TUNEL. Increased mechanical
      stress at the time of reperfusion by treatment with isoproterenol or hyposmotic
      buffer inhibited caspase-3 activity and increased only oncotic myocytes. Co
      treatment with the caspase-3 inhibitor, Ac-DEVD-CHO, and BDM during reperfusion
      inhibited myocyte apoptosis and oncosis but did not inhibit oncosis after
      withdrawal of BDM. CONCLUSIONS: These results suggest that mechanical stress is a
      critical determinant of the form of myocyte death during the early phase of
      reperfusion.

PMID- 16998272
TI  - Effects of ultrasound energy application on cardiac performance in open-chest
      Guinea pigs.
AB  - BACKGROUND: Although ultrasound (US) is widely used in cardiology, little is
      known about the effects of US energy on cardiac performance. This study aimed to
      investigate the mechanical effects of high-intensity continuous US energy (1.0
      MHz with 3 different intensities) on cardiac performance. METHODS AND RESULTS:
      Either left ventricular (LV) pressure or aortic blood flow (ABF) was evaluated in
      open-chest guinea pigs (n=30) under surface ECG monitoring. LV systolic pressure
      and ABF increased significantly (ie, maximum percent increases in these
      parameters were 2.5%, 3.1% and 7.1% for LV systolic pressure and 9.4%, 4.9% and
      8.8% for mean ABF at intensities of 0.06, 0.67 and 2.90 W/cm2, respectively). LV
      end-diastolic pressure was reduced significantly by US (5.3+/-0.9 to 4.8+/-0.8,
      5.5 +/-1.3 to 4.8+/-1.0 and 5.8+/-2.0 to 5.0+/-1.2 mmHg, respectively),
      indicating positive inotropic and lusitropic effects and resultant ABF
      augmentation. Local temperature was not significantly changed. ECG showed neither
      chronotropic action nor arrhythmogenesis. CONCLUSIONS: Although the basic
      mechanisms of these phenomena remain unclear, this pilot study of the short-term
      effects of US energy on cardiac performance suggests the possibility of physical
      therapy for heart failure.

PMID- 16998273
TI  - Autologous bone marrow mononuclear cell implantation induces angiogenesis and
      bone regeneration in a patient with compartment syndrome.
AB  - A 28-year-old man developed compartment syndrome in the right lower leg after
      fracture of the tibia and fibula. Despite fasciotomy, many arteries collapsed and
      union of the tibial and fibula fractures did not occur. Autologous bone marrow
      mononuclear cell (BMMNC) implantation for therapeutic angiogenesis and subsequent
      bone regeneration was performed and 4 weeks later, angiography showed a marked
      increase in collateral vessels surrounding the tibial fracture, and union was
      completed 6 months later. BMMNC implantation therapy might provide therapeutic
      angiogenesis and osteogensis in patients with compartment syndrome.

PMID- 16998274
TI  - Effect of fasudil hydrochloride, a protein kinase inhibitor, on cerebral
      vasospasm and delayed cerebral ischemic symptoms after aneurysmal subarachnoid
      hemorrhage.
AB  - The efficacy and safety of fasudil hydrochloride, a novel protein kinase
      inhibitor, were evaluated for the treatment of cerebral vasospasm and associated
      cerebral ischemic symptoms in patients with ruptured cerebral aneurysm. This
      randomized open trial with nimodipine as the control included 72 patients who
      underwent subarachnoid hemorrhage surgery for ruptured cerebral aneurysm of Hunt
      and Hess grades I to IV. For 14 days following surgery, patients were
      administered either 30 mg of fasudil hydrochloride by intravenous injection over
      a period of 30 minutes three times a day or 1 mg/hr of nimodipine by continuous
      intravenous infusion. Fasudil hydrochloride and nimodipine both showed inhibitory
      effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of
      33 patients in the fasudil group and nine of 32 patients in the nimodipine group.
      Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33
      patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both
      drugs significantly improved consciousness levels and neurological deficits such
      as aphasia. However, fasudil hydrochloride improved motor disturbance more than
      nimodipine. Adverse reactions occurred in 13 of 37 patients receiving fasudil
      hydrochloride and 15 of 35 patients receiving nimodipine. There were no serious
      adverse events in the fasudil group. The results of this clinical trial indicate
      that fasudil hydrochloride is a safe and efficient agent for suppressing cerebral
      vasospasm after subarachnoid hemorrhage surgery for ruptured cerebral aneurysm.

PMID- 16998275
TI  - Histological features of intracranial germinomas not disappearing immediately
      after radiotherapy.
AB  - The histological features of germinomas were investigated to differentiate tumors
      which completely disappear immediately after irradiation and those that persist.
      Eighteen previously untreated patients underwent germinoma biopsy and irradiation
      or combined irradiation and chemotherapy. Four tumors were located only in the
      pineal gland, eight in the suprasellar region, two in multiple locations, one in
      the basal ganglia, and three in other regions. Histologically, the germinomas
      could be divided into type A found in 13 cases which consisted mainly of large
      neoplastic cells and small lymphocytes, the so-called two-cell pattern, and type
      B found in five cases which consisted predominantly of fibrous tissue and
      granulomatous reaction containing occasional neoplastic cells. Follow-up computed
      tomography or magnetic resonance imaging showed the enhanced mass lesion
      disappeared in all cases of type A germinomas within 1 month after treatment, but
      persisted in all cases of type B germinomas for at least 1 month. Type B tumors
      required up to 12 months to show complete radiographic resolution. Persistent
      germinomas consisted predominantly of fibrous tissue and granulomatous reaction
      containing occasional neoplastic cells.

PMID- 16998276
TI  - Penetrating atheroma in cervical carotid artery stenosis.
AB  - A 61-year-old male presented with left hand motor weakness associated with
      cerebral infarction in the right frontal lobe. Right common carotid angiography
      demonstrated a 66% stenosis and carotid duplex scan demonstrated intermediate
      echogenic plaque, indicating typical carotid plaque. Carotid endarterectomy was
      performed 22 weeks after the ischemic onset. During exposure of the carotid
      artery, a soft and yellowish mass (5 x 5 mm) was observed in the lateral wall of
      the carotid bulbus, which was not covered with adventitia but with thin
      connective tissue. The mass was removed en-bloc with a small part of the
      surrounding arterial wall combined with ordinary endarterectomy. The artery was
      closed with a collagen-impregnated polyester patch graft (Hemashield patch) to
      maintain adequate arterial lumen. Histological examination of the removed plaque
      confirmed that atheroma had protruded from the intima through the media as well
      as the adventitia and formed an extra-arterial mass. Such a case requires great
      care to dissect the carotid artery to prevent premature disintegration of the
      atheroma.

PMID- 16998277
TI  - Distal anterior cerebral artery mirror aneurysms and middle cerebral artery
      aneurysms.
AB  - A 52-year-old woman presented with bilateral distal anterior cerebral artery
      (ACA) mirror aneurysms, in addition to two right middle cerebral artery (MCA)
      aneurysms. The left distal ACA and right MCA aneurysms were clipped through right
      interhemispheric and right pterional craniotomies. The right distal ACA aneurysm
      was thrombosed. Distal ACA aneurysms tend to be multiple, but mirror aneurysms
      are rare, especially in the absence of congenital vascular anomaly. Single stage
      unilateral craniotomy is recommended for surgical treatment.

PMID- 16998278
TI  - Surgical treatment of non-ruptured giant occipital arteriovenous malformations
      with frequent migraine-like headache.
AB  - Two patients with giant occipital arteriovenous malformation (AVM) underwent
      microsurgical treatment among 294 patients with intracranial AVM treated between
      1981 and 2004. The patients were aged 52 and 65 years and showed common symptoms
      consisting of long-term frequent migraine-like headaches with visual aura and
      recent homonymous hemianopia. Common neuroimaging findings were abundant dural
      feeders plus feeders from the posterior, middle, and anterior cerebral arteries,
      and deep drainers to the galenic system. Both patients underwent preoperative
      staged embolization and total microsurgical removal of the nidus with a
      neuronavigation system. Both patients returned to ordinary life without the need
      for assistance. These findings emphasize that giant occipital AVM, even if
      unruptured, is surgically treatable with acceptable morbidity.

PMID- 16998279
TI  - Lhermitte-Duclos disease with cervical paraspinal arteriovenous fistula.
AB  - A 38-year-old man presented with a dysplastic cerebellar gangliocytoma associated
      with a paraspinal arteriovenous fistula (AVF) at the upper cervical portion.
      Neuroimaging examination indicated the diagnosis of Lhermitte-Duclos disease. The
      patient was treated by embolization of the AVF followed by partial resection of
      the cerebellar tumor. Genetic examination showed a mutation of the phosphatase
      and tensin homolog deleted on chromosome ten (PTEN) gene. Histological
      examination confirmed the diagnosis. Lhermitte-Duclos disease is a rare
      dysplastic gangliocytoma manifesting as a slowly growing mass in the cerebellum
      and is usually asymptomatic. This case of Lhermitte-Duclos disease associated
      with paraspinal AVF and mutation of the PTEN gene suggests a relationship between
      Lhermitte-Duclos disease and Cowden disease.

PMID- 16998280
TI  - Low-grade astroblastoma recurring with extensive invasion.
AB  - A 17-year-old male presented with morning headache and double vision.
      Neuroimaging revealed a lobulated enhanced mass lesion with a blurred margin and
      remarkable peritumoral edema, and high uptake of methionine. The gray, soft, well
      circumscribed mass was grossly totally resected. Histological examination showed
      the tumor cells were well differentiated with the perivascular pseudorosette
      pattern with broad, non-tapering processes radiating towards a central vessel
      without anaplastic features such as necrosis and endothelial proliferation. The
      histological diagnosis was low-grade astroblastoma. Follow-up magnetic resonance
      imaging demonstrated local recurrence 5 months later. Second surgery was followed
      by adjuvant radiotherapy and combination chemotherapy. Histological examination
      disclosed wide invasion by tumor cells into the subpial and perivascular space of
      the surrounding brain tissue. Follow-up magnetic resonance imaging demonstrated
      further recurrence around the tumor cavity. Surgical removal followed by six
      courses of combination chemotherapy (ifosfamide, cisplatin, and etoposide)
      resulted in complete remission of the tumor. Although gross total resection of
      astroblastoma usually results in long-term survival, some of these yet unfamiliar
      tumors may develop a more malignant character.

PMID- 16998281
TI  - Epidural spinal cavernous hemangioma.
AB  - A 28-year-old woman presented with a rare primary epidural hemangioma without
      adjacent vertebral involvement manifesting as progressive paraparesis. Magnetic
      resonance imaging of the thoracic spine showed an epidural lesion at T4-5 space
      appearing as isointense on T1-weighted images with enhancement by contrast medium
      and hyperintense on T2-weighted images. The lesion was totally removed
      microsurgically. Histological examination revealed cavernous hemangioma. She made
      a complete recovery from her symptoms and has remained asymptomatic for 9 years.

PMID- 16998282
TI  - Long-standing intraspinal glass fragments causing subsequent radiculopathy after
      dorsal stabilization.
AB  - A 37-year-old female presented with a history of lumbar intraspinal glass
      fragments due to an accident in childhood. The patient developed progressive
      right convexity thoracolumbar scoliosis during puberty. Twenty-eight years after
      the accident, horizontalization of this deformity was performed by dorsal
      stabilization. Postoperatively the patient complained of acute L-5 radiculopathy.
      Radiological examination detected multiple glass fragments intra- and
      extradurally around the L3-4 levels with compression of the dural sac.
      Microsurgical removal of the extra- and intradural glass fragments led to
      complete relief of the radicular pain. Foreign bodies can become symptomatic due
      to changes in the status of the spine, especially during growth in young
      patients.

PMID- 16998283
TI  - Simultaneous superficial temporal artery to middle cerebral or anterior cerebral
      artery bypass with pan-synangiosis for Moyamoya disease covering both anterior
      and middle cerebral artery territories.
AB  - Some patients with moyamoya disease treated by conventional surgical procedures
      may develop postoperative refractory ischemia and perioperative cerebral
      infarction in the anterior cerebral artery (ACA) territory. We present a novel
      operative procedure for moyamoya disease to avoid the risk of ischemia in the ACA
      territory, which consists of simultaneous superficial temporal artery (STA) to
      middle cerebral artery (MCA) or ACA bypass with pan-synangiosis, encephalo-duro
      arterio-myo-synangiosis for the lateral frontal and temporal areas, and encephalo
      galeo-arterio-synangiosis for the medial frontal area. This procedure can
      establish direct bypass to the ACA territory at the first intervention.
      Simultaneous STA-MCA and STA-ACA bypasses with pan-synangiosis is suitable for
      patients with moyamoya disease associated with severely impaired perfusion of the
      ACA territory requiring direct bypass surgery.

PMID- 16998284
TI  - [Design and conduct of randomized controlled trials (RCTs)].

PMID- 16998285
TI  - [PIVKA-II as a serological marker of hepatocellular carcinoma].

PMID- 16998286
TI  - [Autoimmune hepatitis: recent update on diagnosis and treatment].
AB  - Autoimmune hepatitis (AIH) is an unresolved, predominantly periportal hepatitis
      that is usually displays hypergammaglobulinemia, and tissue autoantibodies, and
      this malady is responsive to immunosuppressive therapy. Our understanding about
      this clinical entity has been greatly expanded since the first description by
      Waldenstrom 50 years ago. The codified diagnostic criteria of AIH prepared by
      International Autoimmune Hepatitis Group are still valid, but new attempts are
      being made to overcome the shortcomings of this scoring system. Immunosuppressive
      therapies using prednisone and azathioprine are currently the mainstay for the
      treatment of AIH, but there are still many practical questions to be solved.

PMID- 16998287
TI  - [Wilson disease: an update].
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper transport that
      results in accumulation of copper primarily in the liver, the brain and the
      cornea. WD is the most common inherited liver disease with the prevalence of 1:
      37,000 in the pediatric population in Korea. Mutations in the ATP7B gene cause
      failure of copper excretion into the bile and a defective incorporation of copper
      into ceruloplasmin. More than 300 mutations in the ATP7B gene have been described
      so far. Mutations differ between ethnic groups. The p.R778L (an allele frequency
      of 37%), p.A874V (13%), p.L1083F (8%) and p.N1270S (6%) are the common major
      mutations in Korea. Conflicting results on genotype/phenotype correlations of the
      most common mutations have been reported in various countries. There seems to be
      no correlation between the R778L mutation and age of onset or clinical
      manifestations in Korean patients. None of the laboratory parameters alone allows
      a definite diagnosis of WD. In a nation-wide survey of WD, low serum
      ceruloplasmin (<20 mg/dL), high 24 hour urine copper (>100 microgram), high
      hepatic copper content (>250 microgram/g of dry liver) and Kayser-Fleischer rings
      were found in 96%, 86%, 88%, and 73% of the 550 Korean patients respectively. A
      combination of any two of the above 4 laboratory findings is strong support for a
      diagnosis of WD. For the last couple of years, genetic testing has been playing
      an increasingly important role in diagnosing WD. Direct DNA sequencing did
      confirm WD in 98% of the Korean patients. Two mutations were detected in 70% and
      one mutation in 28% of the patients who showed characteristic biochemical and
      clinical findings of WD. Genetic testing, either by haplotype analysis or by
      mutation analysis, is the only reliable tool for differentiating heterozygote
      carriers from affected asymptomatic patients. The agents of the first choice
      among chelators and zinc in specific clinical situations of WD is still a matter
      of debate. Because of frequent side effects and initial neurologic deterioration
      of penicillamine therapy, less toxic trientine or zinc has gradually replaced
      penicillamine over the past few years. Trientine or tetrathiomolybdate has been
      increasingly recommended as the first-line treatment for neurologic WD.
      Currently, liver transplantation is not recommended as primary treatment for
      neurologic WD. Recently published data show that initial zinc therapy for
      asymptomatic/presymptomatic patients and maintenance zinc therapy in patients
      after long term chelation are safe and effective. Further researches and the new
      guidelines on the proper management of patients with WD are needed.

PMID- 16998288
TI  - [Primary biliary cirrhosis].
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease
      that predominantly affects middle-aged women. It is characterized by slowly
      progressive destruction of the small intrahepatic bile ducts together with portal
      inflammation, and this initially leads to fibrosis and later to cirrhosis. It is
      currently accepted that the pathogenesis of PBC is multifactorial with genetic
      and environmental factors interplaying to determine the disease onset and
      progression. In addition to antimitochondrial antibody (AMA), which is the
      hallmark of PBC and is detected in at least 90% of the patients, other
      autoantibodies (antinuclear antibody, anti-smooth muscle antibody and rheumatoid
      factor, etc.) may also be found in the patients. There is no correlation between
      the titer of AMAs and the disease severity. Most patients are diagnosed either
      during the asymptomatic phase of PBC or after presenting with non-specific
      symptoms. Pruritus and fatigue are the most common symptoms of PBC. The prognosis
      of PBC has improved significantly during the last few decades. Patients are now
      diagnosed earlier in its clinical course, they are more likely to be asymptomatic
      at diagnosis and they are more likely to receive medical treatment. A wide
      variety of drugs have been assessed for the treatment of this condition: such
      immunosuppressive agents as corticosteroids, cyclosporine and azathioprine have a
      weak effect on the disease's natural history. Ursodeoxycholic acid (UDCA) is the
      only currently approved medical treatment. For PBC patients with end-stage liver
      disease or an unacceptable quality of life, liver transplantation is the only
      accepted therapeutic option. Early diagnosis and treatment of PBC are important
      because effective treatment with UDCA has been shown to delay disease progression
      and improve rate survival in the early stage.

PMID- 16998289
TI  - [A prospective study comparing the efficacy of early administration of
      terlipressin and somatostatin for the control of acute variceal bleeding in
      patients with cirrhosis].
AB  - BACKGROUND/AIMS: Terlipressin and somatostatin decrease portal venous pressure
      and they are used for the treatment of variceal bleeding. However, only a few
      studies have compared the efficacy of these drugs in combination with other
      procedures for hemostasis. Therefore, we performed a prospective study to compare
      the efficacy of terlipressin and somatostatin for controlling acute variceal
      bleeding when used in combination with other procedures for hemostasis. METHODS:
      A total of 98 patients, who presented with variceal bleeding from September 2003
      to May 2005, were randomly divided into the somatostatin group or terlipressin
      group. We compared the 5-day failure rate (defined as failure to control
      bleeding, rebleeding or death within 5 days of admission) and the 6-week
      mortality. The prognostic factors for 5-day failure and 6-week mortality were
      also evaluated. RESULTS: There were no differences in baseline characteristics
      between the two groups. The overall 5-day failure rate and the cumulative 6-week
      mortality were 16.3% and 15.8%, respectively. The five-day failure rate and the
      cumulative 6-week mortality were not significantly different between the
      somatostatin and terlipressin groups. Hepatocellular carcinoma, the baseline
      serum creatinine level and endoscopic treatment for hemostasis were the
      significant predictors of 5-day failure; the baseline serum creatinine level was
      the predictor of 6-week mortality. CONCLUSIONS: Both somatostatin and
      terlipressin were effective and showed comparable efficacy for the control of the
      acute variceal bleeding in the setting of a combined therapeutic approach. The
      baseline serum creatinine level may be a significant predictor for patient
      failure at 5 days and the 6-week mortality.

PMID- 16998290
TI  - [Comparison of terlipressin and octreotide with variceal ligation for controlling
      acute esophageal variceal bleeding--a randomized prospective study].
AB  - BACKGROUND/AIMS: Terlipressin and octreotide had been used to control acute
      variceal bleeding and to prevent early rebleeding after endoscopic hemostasis. We
      compared the efficacy and safety of terlipressin and octreotide combined with
      endoscopic variceal ligation (EVL) for the treatment of acute esophageal variceal
      bleeding and we evaluated their clinical significance as related to rebleeding.
      METHODS: The eighty eight cirrhotic patients were randomized to the terlipressin
      group (n=43; 2 mg i.v. initially and 1 mg i.v. at every 4 hours for 3 days) or
      the octreotide group (n=45; continuous infusion of 25 microgram/h for 5 days)
      combined with EVL for the treatment of acute esophageal variceal bleeding.
      RESULTS: The initial hemostasis rates were 98% (42/43 cases) in the terlipressin
      group and 96% (43/45 cases) in the octreotide group. The 5-day and 42-day
      rebleeding rates were 12% (5/43 cases) and 28% (12/43 cases), respectively, in
      the terlipressin group and 9% (4/45 cases) and 24% (11/45 cases), respectively,
      in the octreotide group. No significant difference was demonstrated between the
      terlipressin and octreotide groups. The mortality at 42 days was similar in both
      group, but a high mortality rate (48%) was shown to be related to 42-day
      rebleeding. The risk factors related to 42-day rebleeding were Child-Pugh class C
      (aOR=30.2, 95% CI=7.7-117.9), ascites above grade II (aOR=6.6, 95% CI=2.2-19.2)
      and advanced hepatocellular carcinoma (aOR=4.6, 95% CI=1.1-18.9). CONCLUSIONS:
      Comparing terlipressin and octreotide combined with EVL showed them to be equally
      safe and effective therapeutic agents in patients with acute esophageal variceal
      bleeding. The high risk factors related to early rebleeding were poor liver
      function and advanced hepatocellular carcinoma.

PMID- 16998291
TI  - [Effect of endoscopic sclerotherapy using N-butyl-2-cyanoacrylate in patients
      with gastric variceal bleeding].
AB  - BACKGROUND/AIMS: Gastric variceal bleeding is a severe complication of cirrhosis,
      and it has a high mortality rate. This study was conducted to evaluate the
      efficacy of n-butyl-2-cyanoacrylate injection therapy for patients suffering with
      gastric variceal bleeding. METHODS: A total of 86 patients diagnosed with gastric
      variceal bleeding underwent endoscopic n-butyl-2-cyanoacrylate (Histoacryl)
      injection therapy at our department between April, 2002 and July, 2005, with a
      mean follow-up period of 44 weeks (range: 2 to 136 weeks). The initial hemostasis
      rate and the rebleeding rate of endoscopic sclerotherapy were analyzed. Also, the
      cumulative survival rate was analyzed according to the status of hepatocellular
      carcinoma and hyponatremia, the MELD score, the Child-Pugh score and the amount
      of injected Histoacryl. RESULTS: The initial hemostasis rate of Histoacryl
      injection therapy was 93% and the 1 month rebleeding rate was 16.1%. The total
      number of session for treating the initial hemostasis was 1.2+/-0.4 and the total
      volume of Histoacryl was 2.7+/-1.2 mL. The cumulative rebleeding-free rates for
      the patients treated by the Histoacryl injection method at 1 month, 12 months and
      34 months period were 95.1%, 83.2% and 74%, respectively. The cumulative survival
      rates were 78.3% at 1 month, 61.9% at 12 months and 54.6% at 34 months,
      respectively. No thromboembolic phenomenon occurred. According to the Cox's
      proportional hazards analysis, only the MELD score (<15) was an independent
      predicting factor for survival of the patients with gastric variceal bleeding.
      CONCLUSIONS: Endoscopic sclerotherapy using n-butyl-2-cyanoacrylate was a safe
      and effective hemostatic method for patients with gastric variceal bleeding.
      Also, the MELD score (<15) contributed to predicting survival of the patients
      with gastric variceal bleeding.

PMID- 16998292
TI  - [Optimal cut-off value of PIVKA-II for diagnosis of hepatocellular carcinoma-
      using ROC curve].
AB  - BACKGROUND/AIMS: Protein induced by vitamin K absence or antagonist-II (PIVKA
      II), also known as des-carboxyprothrombin (DCP), can be used as an alternative
      tool to alpha-fetoprotein (AFP) for surveillance of hepatocellular carcinoma
      (HCC). The aims of the present study were to compare PIVKA-II levels between the
      patients with HCC and patients with non-HCC chronic liver disease, to evaluate
      the correlation of PIVKA-II and AFP in HCC patients, and finally to estimate the
      optimal cut-off value for PIVKA-II for the diagnosis of HCC with using the
      receiver operating characteristic (ROC) curve. METHODS: A total of 227
      consecutive patients with HCC (n=42) or chronic liver disease (n=185) were
      enrolled in this study. HCC was diagnosed histologically or by imaging such as
      computed tomography, magnetic resonance imaging or angiography. The serum PIVKA
      II and AFP levels were measured by electrochemiluminoimmunoassay with using the
      Haicatch PIVKA-II kit and by immunoradiometric assay, respectively. RESULTS: The
      PIVKA-II level in the HCC patients was significantly higher than the non-HCC
      chronic liver disease patients (903.0+/-1156.7 vs. 111.7+/-211.0 mAU/ mL,
      respectively, P<0.01). PIVKA-II and AFP showed a statistical correlation in HCC
      patients (r=0.46, P<0.01). The sensitivity and specificity of PIVKA-II for the
      diagnosis of HCC were 66.7% and 74.1%, respectively, and when tasted together
      with AFP, the sensitivity was increased by 85.7%. For the ROC curve of PIVKA-II
      in HCC patients, the specificity of a 250 mAU/mL level of PIVKA-II was 95%.
      CONCLUSIONS: PIVKA-II was as useful surveillance tool for differentiating HCC
      from chronic liver disease, and a PIVKA-II value of 250 mAU/ mL was proposed as a
      significant cut-off value for diagnosis of hepatocellular carcinoma.

PMID- 16998293
TI  - [Surgical treatment of sclerosing hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Sclerosing hepatocellular carcinoma (HCC) is an unusual subtype
      of HCC that is characterized by an embedded dense fibrous stroma in the tubular
      neoplastic structures. We aimed to assess the surgical approaches and outcomes of
      sclerosing HCC. METHODS: We retrospectively analyzed the clinicopathologic
      features of 6 patients with sclerosing HCC who underwent surgical treatment at
      Asan Medical Center between July 1989 and December 2005. RESULTS: Six HCC
      patients with sclerosing HCC were diagnosed out of the total 1390 HCC patients
      (0.43%) during the study period. The mean age was 58 years and 4 patients were
      male. Weight loss and abdominal pain were the most common symptoms. The serum
      calcium and phosphorus levels were normal in all the patients. All of them were
      hepatitis B surface antigen-positive, but none was positive for hepatitis C. All
      the lesions were solitary. The tumor size ranged from 45 to 150 mm in diameter
      (median size: 81 mm). We performed right trisegmentectomy (n=1), central
      bisegmentectomy (n=1), right anterior segmentectomy (n=1), ex-vivo resection and
      autotransplantation (n=1) and right posterior segmentectomy (n=2). The median
      overall survival and disease free-survival periods were 24 months and 9.5 months,
      respectively. CONCLUSIONS: The incidence of sclerosing HCC was very low.
      Sclerosing HCC was often not correctly diagnosed before an operation, but
      performing resection prolonged the patients' survival and their prognosis was not
      worse than that for ordinary HCC. Our experience implicates that aggressive
      surgical treatment for sclerosing HCC is beneficial for patient survival.

PMID- 16998294
TI  - [Reappraisal of risk factors predicting liver complications from radiotherapy for
      hepatocellular carcinoma].
AB  - BACKGROUND/AIMS: Determination of the optimal radiotherapeutic parameters for
      radiotherapy of hepatocellular carcinoma (HCC) is still under investigation. The
      purpose of this study is to identify the risk factors associated with radiation
      related morbidity. METHODS: We evaluated one hundred fifty-eight patients, who
      were given radiotherapy for HCC between January 1992 and March 2000. Radiation
      induced liver disease (RILD) was defined as the development of nonmalignant
      ascites without disease progression and an anicteric elevation of the alkaline
      phosphatase level by at least twofold. Gastrointestinal toxicity was assessed by
      using the RTOG-EORTC scale. RESULTS: Six patients (3.8%) displayed RILD. In these
      patients, three patients had not responded to other previous treatments. Two
      patients with portal vein thrombosis or huge sized mass, above 10 cm, showed
      liver toxicity and two other patients presented with Child-Pugh class B liver
      cirrhosis. Eight patients (5%) had gastro-duodenal ulcers. In one of these 8
      patients, the left lobe close to the stomach was involved and two patients had
      been treated for gastro-duodenal ulcer. In two more patients, the radiation
      field, with using anterior/posterior radiation ports, covered a significant
      volume of the gastrointestinal tract. One of eight patients had been irradiated
      with a large fraction size (250 cGy). CONCLUSIONS: The efforts should be made to
      reduce the radiation-related complications for hepatocellular carcinoma by
      considering the volume and the function of remaining liver, the location of
      tumor, the tumor size and the severity of liver cirrhosis.

PMID- 16998295
TI  - [Inflammatory pseudotumor of liver--a clinical review of 15 cases].
AB  - BACKGROUND/AIMS: Inflammatory pseudotumor rarely occurs in the liver. However, it
      is important to discriminate it from malignant hepatic tumor in order to avoid
      unnecessary surgery. We aimed to elucidate the characteristic features of this
      disease entity by analyzing our experiences and by reviewing the related
      literatures. METHODS: Fifteen patients were enrolled during a recent three-year
      period. The patients were pathologically diagnosed with inflammatory pseudotumor
      of the liver, and their clinical and imaging findings were analyzed
      retrospectively. RESULTS: Our study population was composed of ten men and five
      women, and their mean age was 60.3+/-9.2 years. Their initial diagnoses were
      inflammatory pseudotumor (n=8), malignant tumors (n=3) and abscess (n=4). Twelve
      of 15 patients were associated with biliary diseases such as biliary stone,
      gallbladder cancer, empyema or cholangiocarcinoma. The most common symptom was
      abdominal pain. The most common CT and MR findings could be summarized as a
      delayed hyperattenuating mass with an internal hypoattenuating component. The
      tumors were solitary in 13 patients and multiple in two patients. The lesions
      regressed spontaneously in seven patients. Four patients were treated by
      antibiotics and 3 patients by surgical resection. CONCLUSIONS: Inflammatory
      pseudotumor of the liver seems to have relatively common clinical and imaging
      features, as described above. However, these features are not disease-specific;
      thus, preoperative histologic confirmation is necessary to avoid unnecessary
      surgery.

PMID- 16998296
TI  - A case of needle tract implantation of hepatocellular carcinoma after
      percutaneous biopsy with an 18G Tru-cut needle.
AB  - Needle tract implantation of hepatocellular carcinoma (HCC) is a rare
      complication of percutaneous biopsy, and it is largely associated with end
      cutting needles or aspiration biopsy. The CT findings that have been reported
      include oval or round soft tissue nodules with persistent contrast enhancement
      along the needle tract, mostly in the subcutaneous tissue or the intercostal
      muscle layers. In this report, we describe a case of needle tract implantation of
      HCC after US-guided percutaneous biopsy with an 18G tru-cut needle.

PMID- 16998297
TI  - [A case of Bell's palsy associated with peginterferon Alfa-2a and ribavirin
      therapy for chronic hepatitis C virus infection].
AB  - Pegylated interferon alfa-2a (PEG-IFN) and ribavirin combination therapy is the
      first line treatment for chronic HCV infection. There are four reports of Bell's
      palsy associated with interferon-alpha (IFN-alpha) and ribavirin therapy. We
      report here a case of Bell's palsy that occurred in a patient with chronic HCV
      infection during combination PEG-IFN and ribavirin therapy. The patient was 49
      year-old man with chronic hepatitis C for 2 years. The liver biopsy showed grade
      1 and stage 1. Therapy with PEG-IFN (Pegasys) 180 microgram/week and ribavirin
      1200 mg/day was initiated. After 3 weeks of treatment, the patient showed a loss
      of muscular tone on the left side of his face. A diagnosis of Bell's palsy was
      made, and the PEG-IFN and ribavirin therapy was stopped. Prednisolone 45 mg/d was
      given and then tapered for 8 weeks. His palsy improved over 6 weeks.

PMID- 16998299
TI  - [Nonalcoholic steatohepatitis].

PMID- 16998298
TI  - [A case of complete regression of hepatocellular carcinoma during administration
      of COX-2 inhibitor].
AB  - Overexpression of cyclooxygenase-2 (COX-2) has been associated with
      hepatocarcinogenesis. Inhibitors of COX-2 have proapoptotic and antiproliferative
      effects on malignant tumors and inhibit tumor invasion to the surrounding
      tissues. We report here a case of complete regression of advanced hepatocellular
      carcinoma (HCC) during COX-2 inhibitor administration. An eighty-year-old female
      was diagnosed as an advanced HCC, which was associated with HCV infection. She
      received COX-2 inhibitor for 3 months due to degenerative arthritis of both
      knees. Tumor enhancement on arterial phase CT completely disappeared without
      specific treatment for the HCC, and the tumor size decreased on the follow-up CT
      scan.

PMID- 16998300
TI  - [Focal peliosis hepatis mimicking hepatocellular carcinoma].

PMID- 16998301
TI  - [Prevention of variceal bleeding and measurement of hepatic vein pressure
      gradient].

PMID- 16998302
TI  - Benefits and adverse effects of anti-emetic glucocorticoids in cancer.

PMID- 16998303
TI  - Cancer therapy: back to metabolism.

PMID- 16998304
TI  - A role for CaM-kinases in the cellular response to oxidative stress?

PMID- 16998315
TI  - From krukenberg to today: the ever present problems posed by metastatic tumors in
      the ovary: part I. Historical perspective, general principles, mucinous tumors
      including the krukenberg tumor.
AB  - This review considers historical aspects of metastatic tumors to the ovary,
      general principles that aid in their evaluation, and metastatic mucinous tumors,
      including the Krukenberg tumor. The historical timeline on the Krukenberg tumor
      dates back to the legendary Sir James Paget and the story is followed through the
      well-known, albeit flawed, contribution of Friedrich Krukenberg and others who
      have contributed important papers over the years, including the overlooked
      contribution of the French investigator Gauthier-Villars. Knowledge of metastatic
      colorectal carcinoma is traced back to the famed British surgeon Sir John Bland
      Sutton and followed through to more recent contributions, including the important
      one of Lash and Hart. Contributions on mucinous tumors conclude the historical
      perspective, note being made of the recent evidence suggesting that the long held
      contention of Dr Robert E. Scully that ovarian mucinous tumors in patients with
      pseudomyxoma peritonei usually originate from the appendix is correct. The
      section on general principles highlights the many clinical, gross, microscopic,
      and special techniques such as immunohistochemistry that may aid in determining
      that an ovarian tumor is metastatic with emphasis on the first 3 mentioned
      aspects. Problematic features such as a tendency for metastatic tumors to be
      cystic, even when the primary tumors are not, and for many metastatic tumors to
      mature in the ovary (so-called maturation phenomenon), are emphasized. Of the
      many helpful findings that resolve the problem, the characteristic features of
      surface implants are highlighted. The contribution on the Krukenberg tumor
      reviews the varied microscopy of this tumor pointing out that the well-known
      pattern of signet-ring cells in a cellular stroma, albeit characteristic, is
      often not striking and frequently overshadowed by other microscopic features. The
      latter include, in many cases, a rather unique microcystic pattern. The final
      portion of the essay reviews mucinous tumors of non-Krukenberg type, beginning
      with those that originate from the appendix. The appendiceal neoplasms have
      distinctive features in most cases being particularly well differentiated, and
      this is also seen in their ovarian metastases. Other mucinous tumors that
      commonly simulate closely metastatic neoplasms, include those from the pancreas
      in particular, but also diverse other sites, are then reviewed.

PMID- 16998316
TI  - Assessing the utility of a mutational assay for B-RAF as an adjunct to
      conventional fine needle aspiration of the thyroid gland.
AB  - Thyroid carcinoma is the most common endocrine malignancy; it is typified by a
      number of classical genomic insults, which tend to cluster with the discrete
      histologic subtypes. The most common of these is a mutation in B-RAF, which is
      present in approximately 44% (29% to 83%) of cases. In this review we have
      assessed the potential utility of a molecular test for somatically acquired
      mutations in B-RAF using thyroid malignancy as a model system according to 3
      fundamental questions: would a test enhance our ability to distinguish benign
      from malignant, would a test unveil a risk factor not otherwise known, and would
      detecting a mutation enable a therapeutic option specific to those patients who
      carry the mutation?

PMID- 16998317
TI  - Diagnostic Immunohistochemistry: what can go wrong?
AB  - Although immunohistochemistry (IHC) has become an integral component of the
      surgical pathology laboratory and practice, it remains a subspecialty in search
      of a definition. The rapid expansion of this discipline is continually
      contributing to the struggle of interested pathologists and technologists to
      identify the proper working conditions of antibody reagents and the right choice
      of detection systems and instrumentations. Training programs have not, for the
      most part, successfully incorporated IHC in their curricula. Thus, pitfalls in
      diagnostic IHC, in our opinion, are becoming more frequent than they used to. In
      this review, we highlight and attempt to provide solutions for the most common
      pitfalls in diagnostic IHC as it relates to the routine practice of surgical
      pathology.

PMID- 16998318
TI  - Nephrogenic adenoma: an update on an innocuous but troublesome entity.
AB  - Nephrogenic adenoma (NA) is a rare benign lesion of the urothelial tract that is
      typically preceded by some form of genitourinary insult. The pathogenesis of NA
      is not entirely clear. Although generally presumed to be a metaplastic process of
      the urothelium, recent evidence suggests that NA may in fact be derived from
      detached renal tubular cells implanting along the urothelial tract in previously
      injured areas, at least in cases associated with a kidney transplant. On light
      microscopy, NA shows a variety of patterns, including tubulocystic, papillary,
      and much less frequently solid, that often coexist. Recognition of its
      characteristic patterns, and awareness of its unusual architectural and cytologic
      features, is key to making the diagnosis of NA and distinguishing this lesion
      from malignant neoplasms occurring at the same sites, in particular, clear cell
      carcinoma, nested or microcystic variants of urothelial carcinoma and prostatic
      adenocarcinoma. Although straightforward in most cases, the correct diagnosis may
      be difficult to make on limited tissue samples. A number of immunohistochemical
      markers have been studied in an attempt to characterize NA; however, to date
      there is no specific immunohistochemical profile to distinguish this lesion from
      its malignant mimickers, although PAX2, a new marker, may prove to be helpful in
      this regard. Clinicopathologic correlation with careful attention to morphology
      remains the pillar in establishing the correct diagnosis.

PMID- 16998319
TI  - Transient leukemia (transient myeloproliferative disorder, transient abnormal
      myelopoiesis) of Down syndrome.
AB  - Transient leukemia of Down syndrome (DS-TL), also known as transient
      myeloproliferative disorder of Down syndrome (DS) and transient abnormal
      myelopoiesis of DS, occurs in approximately 10% of DS neonates and in
      phenotypically normal neonates with trisomy 21 mosaicism. In DS-TL, peripheral
      blood analysis shows variable numbers of blasts and, usually, thrombocytopenia;
      other cytopenias are uncommon. Bone marrow characteristics of DS-TL are,
      likewise, variable, though (in contrast to other leukemias) the bone marrow blast
      differential can be lower than the peripheral blood blast differential. The
      blasts of DS-TL typically show light microscopic, ultrastructural, and flow
      cytometric evidence of megakaryocyte differentiation. DS-TL neonates have a
      approximately 15% risk of developing potentially fatal liver disease and show
      <10% incidence of hydrops fetalis. Additional manifestations of DS-TL include
      cutaneous involvement, hyperviscosity, myelofibrosis, cardiopulmonary failure,
      splenomegaly, and spleen necrosis. Despite its typical transient nature, 20% to
      30% of DS-TL patients develop overt (nontransient) acute leukemia, usually within
      3 years and typically of the M7 phenotype (acute megakaryoblastic leukemia). The
      pathogenesis of DS-TL (and of subsequent acute leukemia) involves mutation of
      GATA1 (on chromosome X), which normally encodes a transcription factor integral
      to normal development of erythroid, megakaryocytic, and basophilic/mast cell
      lines. The pathogenetic role of trisomy 21 in DS-TL is unclear. Though
      indications for chemotherapy in DS-TL have not been firmly established, the
      blasts of DS-TL are sensitive to low-dose cytosine arabinoside.

PMID- 16998320
TI  - Controversies in the assessment of HER-2: more questions than answers.
AB  - Human epidermal growth factor receptor 2 (HER-2) is over-expressed in 15% to 30%
      of breast cancers and is a poor prognostic marker in node-positive patients. HER
      2 expression is an indicator of greater sensitivity to anthracycline-based
      chemotherapy and is the major criterion for selection for treatment with the anti
      HER-2 antibody trastuzumab (Herceptin). Fluorescence in situ hybridization and
      immunohistochemistry (IHC) are the 2 most commonly used methods for detection of
      the gene and protein, respectively. Criticisms have been levied at the IHC method
      of identifying HER-2 overexpression but convenience and costs of this technique
      cannot be overlooked. Modifications to the IHC technique and scoring accommodate
      for many of the problems that derive from variables in preanalytical and analytic
      factors that influence results but standardization is currently impossible to
      attain. Deficiencies in fluorescence in situ hybridization assay also exist and
      alternative molecular methods of assay are explored in this review.

PMID- 16998321
TI  - Signal transduction cross-talk during colorectal tumorigenesis.
AB  - Colorectal carcinoma (CRC) is the second leading cause of cancer-related death in
      the United States in the general population (men and women combined).
      Epidemiologic data obtained over the last several decades shows convincing
      evidence for the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in the
      reduction of risk of CRC through the inhibition of cycloxygenase (COX). Recent
      research has also demonstrated that prostaglandin E2 (PGE2), a predominant
      product of COX, plays a critical role in tumorigenesis of CRCs through its
      guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs), EP2,
      and EP4. Molecular analysis of CRC and its precursor lesions have shown that
      mutation of Adenomatous Polyposis Coli (APC), a gene involved in the wingless
      type signaling pathway, is an early event during the neoplastic progression in
      the majority of sporadic CRCs. The fundamental questions are: why is wild type
      APC so important in adult colorectal tissues in preventing this tumorigenesis,
      and what are the mechanisms by which NSAIDs prevent colorectal tumorigenesis? We
      reviewed the recent literature concerning the PGE2-GPCR signaling pathway and the
      APC-beta-catenin (wingless type) pathway in CRC cells and propose a unifying
      schema regarding the tumorigenesis of CRC. Colorectal epithelia are continuously
      exposed to various extracellular agonists (including low levels of PGE2). The
      binding of these agonists to their corresponding GPCRs leads to formation of
      activated Galphas, which in turn activates beta-catenin. In normal colorectal
      epithelia, wild type APC blocks the Galphas-induced activation of beta-catenin,
      and therefore maintains homeostasis and prevents tumorigenesis. In contrast, in
      the absence of functional APC, continuous formation of activated Galphas by the
      binding of various extracellular agonists to their receptors leads to the
      activation and nuclear accumulation of beta-catenin. This elevated nuclear beta
      catenin in turn increases transcription of many genes (COX-2, C-myc, Cyclin D1,
      vascular endothelial growth factor, T cell factor, etc.) involved in
      tumorigenesis. Increased transcription of COX-2 also leads to excessive
      production of PGE2 that in turn forms a stimulatory loop with many biologic
      functions (proliferation, migration, invasion, angiogenesis, and inhibition of
      apoptosis), which may result in the development of CRC. Because NSAIDs inhibit
      COX and decrease the production of PGE2, interruption of the cycle helps prevent
      colorectal tumorigenesis.

PMID- 16998322
TI  - Google as a pathology portal.

PMID- 16998323
TI  - Mastopexy with autologous augmentation after massive weight loss: the intercostal
      artery perforator (ICAP) flap.
AB  - The reconstruction of breast and upper-body deformities in massive weight loss
      (MWL) patients presents specific challenges to the plastic surgeon. In addition
      to significant breast ptosis and loss of breast volume, bariatric patients also
      have excessive lateral axillary and posterior truncal tissue that may require
      dermolipectomy for correction. A wise-pattern mastopexy was designed with a
      pedicled fasciocutaneous flap based on the intercostal artery perforators (ICAP)
      to correct breast ptosis, to restore breast volume, and to eliminate redundant
      upper truncal tissue. Five MWL patients underwent mastopexy with ICAP flap
      augmentation. All patients had stable and esthetically pleasing results 1, 3, and
      6 months postoperatively. There were no complications of infection, wound
      dehiscence, seroma, or hematoma. Furthermore, there was no evidence of flap loss
      or tissue necrosis. Mastopexy with autologous augmentation using the ICAP flap
      was found to be a reliable method of breast reconstruction in the MWL patient.

PMID- 16998324
TI  - The "banked" TRAM: a method to insure mastectomy skin-flap survival.
AB  - BACKGROUND: Necrosis of the skin flaps after mastectomy can be a devastating
      complication following immediate breast reconstruction with a TRAM flap. Skin
      flap loss compromises the aesthetic result and may necessitate revisional
      surgery. The authors wish to present a simple and effective method to insure
      mastectomy skin-flap survival. METHODS: Seven patients over the last 5 years were
      treated with immediate breast reconstruction with a TRAM flap after skin-sparing
      mastectomy and had evidence of skin-flap compromise intraoperatively. These
      patients had their TRAM flaps "banked" under the flaps and returned to the
      operating room within 72 hours for definitive debridement of the skin flaps,
      deepithelialization, and insetting of the TRAM. RESULTS: In all cases, there was
      100% survival of the skin flaps after delayed insetting. There was no skin-flap
      loss. No patients required additional surgery for revision. CONCLUSIONS: The
      banked TRAM is a simple and effective method to insure mastectomy skin flap
      survival if there is a question of flap viability.

PMID- 16998325
TI  - Lighted retractor-assisted transaxillary approach in gynecomastia correction.
AB  - Gynecomastia is an excessive development of the male breast. Surgery is the
      accepted standard method for treatment. In our department, 5 male patients
      ranging in age from 18 to 24 years who had grade I-IIA-IIB gynecomastia according
      to Simon's classification were operated on with a lighted retractor-assisted
      transaxillary approach. Dissection, excision, and hemostasis were performed under
      direct vision by using the lighted retractor. The glands and adjacent fat were
      removed en bloc. The axillary scar was barely visible. The patients were
      satisfied with the results. Gynecomastia correction with a lighted retractor
      assisted transaxillary approach is feasible for those who have grade I-IIA-IIB
      gynecomastia according to Simon's classification and also for those who do not
      want to have scars on their breasts' esthetic units and have a tendency towards
      keloid formation. Scars can be kept in the hidden area, with no considerable
      complication. The lighted retractor facilitates the transaxillary approach and
      provides appropriate dissection, excision, and hemostasis.

PMID- 16998326
TI  - Mastectomy scar histopathology of limited clinical value.
AB  - This study assesses whether the routine submission of mastectomy scars for
      histologic examination at the time of delayed breast reconstruction is useful. A
      retrospective review was performed of all delayed breast reconstructions for
      breast cancer performed by a single surgeon over a 5-year period from January
      2000 to December 2004. One hundred eighty-eight patients underwent delayed breast
      reconstruction during this period, and of these, 133 scars (1 patient had
      bilateral scars excised) were submitted for histology where the reconstruction
      was performed by either transversus rectus abdominus muscle flap (TRAM) or
      latissimus dorsi myocutaneous flap (LDF) +/- implant. Fifty-six patients had
      reconstruction performed by tissue expander through the inframammary crease where
      the original mastectomy scar was not excised and were excluded from the study.
      One mastectomy scar specimen showed a 2-mm suspicious area of invasive ductal
      carcinoma consistent with same histopathology at the time of mastectomy. This
      study corroborates evidence that it is questionable whether routine
      histopathology of mastectomy scar at the time of delayed breast reconstruction
      should not be a standard practice.

PMID- 16998327
TI  - Early postoperative adjustment of blepharoptosis.
AB  - The challenge of accurately predicting eyelid height after blepharoptosis surgery
      is a well-known problem even in competent hands. From May 1988 to December 2004,
      the authors reviewed 182 cases (240 eyes) of blepharoptosis corrected by
      frontalis muscle transfer or levator resection and had experienced 10 cases (15
      eyelids) of early adjustment around 1 week. The period from initial operation to
      adjustment is between 6 and 8 days, and the mean period is 7 days. Initial
      operative procedures were frontalis muscle transfer in 3 cases (4 eyelids) and
      levator resection in 7 cases (11 eyelids). Follow-up period ranged from 6 months
      to 16 years. Early postoperative adjustment was performed in accordance with the
      preoperative and postoperative degree of ptosis of the patient and considering
      previous operative technique. The results are evaluated according to the criteria
      of an ideal correction by Souther and Jordan. Seven patients had good or
      satisfactory results (less than 1 mm asymmetry, good in 5 cases and satisfactory
      in 2 cases). Three patients (5 eyelids) were recorded as poor results (more than
      2 mm asymmetry). Even if early or late reoperation can be effective in correcting
      unsatisfactory results after correction of blepharoptosis, early reoperation is
      better than later reoperation because early reoperation can offer a reduction in
      time to final result, the ease with which it is performed, potential cost
      savings. The experience of the surgeon is also an important factor for the
      treatment of recurred blepharoptosis.

PMID- 16998328
TI  - Technique for blepharoptosis correction using double-breasted orbicularis oculi
      muscle flaps.
AB  - BACKGROUND: The technique that uses the orbicularis oculi muscle flap to elevate
      the upper eyelid has become a popular surgical alternative for blepharoptosis.
      This method is especially effective in cases of severe blepharoptosis with poor
      levator muscle function. In this technique, the superiorly based orbicularis
      oculi muscle flap (which is connected to the frontalis muscle anatomically) is
      advanced and attached to the tarsal plate, thus enabling dynamic elevation of the
      upper eyelid. However, a temporary period of lagophthalmos occurs with the
      original method. Although the problem is temporary, it typically lasts 2 to 6
      months and may lead to serious eye emergencies. METHODS: We describe a
      modification that eliminates lagophthalmos, which is the main drawback of the
      original technique. Two orbicularis oculi muscle flaps are created, one
      superiorly based and one inferiorly based. The inferiorly based flap corresponds
      to the strip of pretarsal orbicularis oculi that is considered "excess" and is
      discarded in other methods. Our aim with this modified technique is to preserve
      as much of the pretarsal part of the orbicularis oculi muscle as possible, and
      thus enable immediate tight eyelid closure postoperatively and achieve dynamic,
      powerful eyelid-opening action. RESULTS: We have used this technique in 7
      patients (11 eyelids total) during the past 5 years and have achieved favorable
      results. All 11 operated eyelids showed immediate tight closure postoperatively,
      as well as dynamic, powerful eyelid-opening action. CONCLUSION: This operation is
      a good alternative for patients with severe ptosis who have insufficient levator
      function and for cases that have recurred after operations with other methods.
      Local native tissues are used and dynamic correction is achieved with a single
      incision. The need for intensive eye care is eliminated and there is less risk of
      corneal damage in the early postoperative period. Above all, this technique
      yields predictable eyelid-opening action.

PMID- 16998329
TI  - Clinical outcome of peripheral nerve decompression in diabetic and nondiabetic
      peripheral neuropathy.
AB  - Surgical decompression of peripheral nerves in patients with diabetes was
      reported to restore sensation and improve function. In this study, a
      retrospective review of 12 diabetic and 20 nondiabetic patients with lower
      extremity peripheral neuropathy who underwent surgical decompression was
      performed. Clinical evaluation by Tinel test, muscle power examination, and 2
      point discrimination were performed preoperatively, at 6 months, and between 9
      and 15 months postdecompression. Clinical outcomes were classified into
      excellent, good, or fair based on improvement in symptoms and return of function.
      Thirty-two patients underwent 36 surgeries, in which 99 lower-extremity nerves
      were decompressed. There was a statistically significant improvement in muscle
      function (P < 0.001) and 2-point discrimination for the small toe (P = 0.008) and
      big toe (P = 0.038). At a mean of 7.7 months, 90% of patients showed significant
      improvement in pain and function. It is concluded that surgical decompression was
      associated with significant improvement in clinical outcome in patients with
      diabetic and idiopathic neuropathy with evidence of superimposed compression.

PMID- 16998330
TI  - Sural nerve donor-site morbidity: thirty-four years of follow-up.
AB  - This study presents a long-term evaluation of sural nerve donor-site morbidity in
      patients with at least 15 years' follow-up (mean 26 years) after sural nerve
      harvesting for peripheral nerve repair. Twenty-nine patients (mean age 30 years
      at time of surgery) participated in a retrospective analysis using a
      questionnaire. The subjective patient evaluations indicated a significant
      recovery of the sural nerve donor site with regard to sensory loss, pain, and
      cold sensitivity over time. Beyond 5 years, no further improvement is to be
      expected. Our findings provide a guideline for general patient information
      regarding sural nerve donor-site morbidity. An area of sensory loss of
      approximately the size of 5 x 6 cm is to be expected, and 20%-30% of the patients
      experienced minimal levels of pain, cold sensitivity, functional impairment, and
      scar discomfort. The latter 2 were confined to inconvenience with bumping of the
      donor site and putting on shoes.

PMID- 16998331
TI  - A novel flap to repair medial and lateral malleolar defects: anterior tibial
      artery perforator-based adipofascial flap.
AB  - Soft tissue coverage of the ankle is a difficult challenge. The adipofascial flap
      based on perforators of the anterior tibial artery was harvested from the dorsum
      of the foot and used for repairing of soft tissue defects either on the lateral
      or medial malleolar region in 7 patients. Two medial and 5 lateral malleolar
      defects were covered using the flap described. The size of flaps varied from 3.5
      x 10 cm to 4.5 x 12 cm. All flaps had good perfusion and survived completely.
      Donor-site morbidity was minimal in all cases. Both functional and esthetical
      results were satisfactory. Because of thin and pliable features, this flap is
      suitable for repair of defects around the ankle region. In addition, donor-site
      morbidity of this flap is minimal, with an acceptable scar hidden in the shoe
      wearing area.

PMID- 16998332
TI  - Laryngotracheal reconstruction using a rigidly fixated split clavicular
      myoosseous flap: a 10-year review.

PMID- 16998333
TI  - Skin regeneration for children with burn scar contracture using autologous
      cultured dermal substitutes and superthin auto-skin grafts: preliminary clinical
      study.
AB  - We have evaluated a novel treatment of burn scar contracture in children. This
      method involves the application of an autologous cultured dermal substitute
      (CDS), followed by a graft of superthin split-thickness skin. In the first
      operation, the autologous CDS was applied to the skin defect that had occurred
      after releasing the scar contracture. In the second operation, a superthin
      thickness skin graft (4 approximately 6/1000 inches) was applied 5 approximately
      12 days after the first operation. The autologous CDS was applied to 10 sites of
      5 children. On 8 sites, the skin grafts were contracted to some extent at an
      early stage. However, these skin grafts were stretched gradually to a range from
      60% to 100% of an original size. At 2 sites, the skin grafts had stretched from
      110% to 130% of the original size. This strategy may be useful for the treatment
      of burn scar contracture in children.

PMID- 16998334
TI  - Treatment of facial angiofibroma of tuberous sclerosis using cultured epithelial
      autografts.
AB  - Treatment of facial angiofibroma of tuberous sclerosis is problematic, because
      the skin lesions involve entire dermis. Five patients aged from 14 to 33 (mean:
      23.6) years old with angiofibroma of tuberous sclerosis were treated with
      cultured epithelial autografts between 1995 and 2004. The entire area of the
      facial lesions was excised using a razor to remove large nodules, and then the
      remaining lesions were further abraded to a rather deep layer of the dermis to
      smooth the skin and remove small nodules. Then a cultured autologous epithelium
      was grafted onto the wound. In all patients, epithelization was complete within
      10 (mean: 9) days after the surgery. All patients were followed up for more than
      6 months and showed neither depigmentation due to scar formation nor hypertrophic
      scars. In some patients, some pebbly regrowth had occurred at 5 years
      postoperatively, but the appearance was quite acceptable.

PMID- 16998335
TI  - Maintenance of subcutaneous cavities with CO2.
AB  - Since mechanical retractors in endoscopic plastic surgery cause certain
      drawbacks, we developed a model in dogs, which, by insufflating CO2 into a
      subcutaneous cavity, we were able to maintain. We evaluated the magnitude of
      subcutaneous emphysema and absorption of CO2 by insufflating different pressures
      and the efficacy of external pressure on the skin with the purpose of limiting
      the subcutaneous emphysema. Sixteen dogs were divided in 3 groups, A, B, and C.
      We controlled the pulmonary function by using a volume-cycle ventilator. In all
      groups, we maintained a subcutaneous cavity by insufflating CO2. Groups A and C
      were insufflated at 15 mm Hg; group B, at 8 mm Hg. We placed circumferential
      Esmarch bandages on the thorax of groups B and C to delimit superiorly and
      inferiorly the surgical area. Arterial blood gas analyses (ABGA) were taken from
      the femoral artery 60 minutes after intubation, 60 minutes after Esmarch bandage
      was placed and at the end of the CO2 insufflation. Statistically, results were
      analyzed by Wilcoxon test. P < 0.05 was considered statistically significant.
      Group A showed extensive subcutaneous emphysema. Two dogs died. The systemic
      increase of the CO2 showed a median of 9.6 mm Hg (P < 0.05). In Group B, Esmarch
      bandages caused increase in CO2, with a median of 1.65 mm Hg (P < 0.028). None of
      these dogs showed subcutaneous emphysema during the insufflation after CO2
      insufflation pressure augmented with a median of 3.7 mm Hg (P < 0.028). In Group
      C, chest restriction increased CO2 median of 6.1 mm Hg (P < 0.043), and
      subcutaneous emphysema shown was less extensive than group A. The CO2 increased
      after insufflation a median of 16 mm Hg (P < 0.043). CONCLUSIONS: Subcutaneous
      cavities can be maintained open with CO2 insufflation at 8 mm Hg, limiting
      perfectly the surgical area; as done with Esmarch bandages, it reduces CO2
      absorption and makes this procedure safe.

PMID- 16998336
TI  - Applications of bilateral vascularized femoral bone marrow transplantation for
      chimerism induction across the major histocompatibility (MHC) barrier: part II.
AB  - Bilateral vascularized bone marrow transplant (VBMT) model was designed to induce
      chimerism across the major histocompatibility (MHC) barrier under combined
      alphabeta T-cell receptor monoclonal antibody and cyclosporine A (alphabeta
      TCRmAb/CsA) protocol. Seventeen transplants were performed between BN(RT1) donors
      and Lewis(RTI) recipients. Group I, isograft controls; Group II, allografts
      rejection controls; Group III, allografts under 7-day protocol of alphabeta
      TCRmAb/CsA. Donor bilateral femoral bones were bilaterally anastomosed to the
      abdominal aorta and inferior vena cava of recipient. At day 7
      posttransplantation, all bone flaps were viable. Groups I and III survived
      without signs of rejection. In Group III, peak level of chimerism in peripheral
      blood was evaluated at day 21 (24.2%), at day 63 declined to 1.5%, and was
      maintained at this level thereafter. Donor-derived cells were present in the bone
      marrow of recipients at 28.2% at day 21 posttransplant. Histology confirmed
      viability of bone marrow cells in isograft during the entire follow-up and up to
      35 days in treatment Group III. Bilateral VBMT induced donor-specific chimerism
      across the MHC barrier under the immunomodulatory protocol of alphabeta
      TCRmAb/CsA.

PMID- 16998337
TI  - The effect of ischemic preconditioning on secondary ischemia in skin flaps.
AB  - Ischemic preconditioning is a useful manipulation to reduce the undesirable
      effects of ischemia. The beneficial results of this phenomenon against ischemia
      reperfusion have been seen in different flap models; however, all these studies
      have focused on primary ischemia. In this study, we investigated the effects of
      ischemic preconditioning on secondary ischemia in a skin flap model. We used the
      6- x 3-cm-sized epigastric skin flap in 40 Wistar rats. In all animals, primary
      global ischemia of 2 hours was followed by 4 hours of either arterial or venous
      secondary ischemia 24 hours after the primary ischemia and ischemic
      preconditioning (IP) was tested in this protocol. Ischemic preconditioning was
      performed by 2 cycles of 15 minutes of repeated ischemia/reperfusion periods. The
      animals were allocated into 4 groups: group 1 (n = 10 animals): primary ischemia
      (2 hours) + secondary arterial ischemia (4 hours); group 2 (n = 10 animals): IP +
      primary ischemia (2 hours) + secondary arterial ischemia (4 hours); group 3 (n =
      10 animals): primary ischemia (2 hours) + secondary venous ischemia (4 hours);
      group 4 (n = 10 animals): IP + primary ischemia (2 hours) + secondary venous
      ischemia (4 hours). Flap viability was assessed 1 week after the surgical
      procedure, and surviving flap area was recorded as a percentage of the whole flap
      area. Group 1 was compared with group 2, and group 3 was compared with group 4 to
      evaluate the effects of ischemic preconditioning against secondary arterial and
      venous ischemia. t test and Mann-Whitney rank sum tests were used for statistical
      analysis. There were statistical differences both between groups 1 and 2 and
      groups 3 and 4. The results revealed that ischemic preconditioning was an
      effective procedure to reduce the flap necrosis as a cause of secondary ischemia
      in skin flaps.

PMID- 16998338
TI  - Successful salvage of ventricular-assist devices in the setting of pump pocket
      infection.
AB  - Implantable ventricular-assist devices (VADs) have been approved for use both as
      a bridge to heart transplantation and as a destination therapy. Rising numbers of
      patients are surviving with these devices for several years. However, infections
      of these foreign bodies are serious and frequent complications, often requiring
      removal of the implant, with serious health consequences. Given the increased use
      of VADs as life-preserving destination therapy, explantation of these devices in
      the face of infection is impractical. We evaluated and successfully treated 2
      patients with VAD pocket infections referred by the cardiac surgery service at
      our institution using aggressive surgical and pharmacologic therapy, with the
      goal of preserving the VADs. However, this is still a largely unsolved dilemma
      requiring further exploration into prevention and treatment since these
      devastating infections will likely become a more frequent reconstructive
      challenge.

PMID- 16998339
TI  - Swelling of the breast following augmentation mammaplasty and minimally invasive
      cardiac surgery.
AB  - Complications following breast augmentation procedures occur in the acute
      setting, usually in the form of hematoma, seroma, wound breakdown or infection.
      Late complications of augmentation mammaplasty usually manifest as either a
      failure of the prosthesis (eg, leak, rupture) or capsular contracture. We present
      an interesting case of a hematoma following augmentation mammaplasty that
      occurred 7 years postoperatively. What makes this case particularly intriguing is
      that in the time period between the augmentation mammaplasty and the late
      hematoma, the patient underwent minimally invasive cardiac surgery to treat a
      malfunctioning mitral valve. Ultimately, the breast implant was salvaged and the
      patient obtained a very satisfactory result. This case is important to report
      because as more women choose to have breast augmentation procedures and as more
      people have minimally invasive cardiac surgery, this clinical scenario will be
      encountered with greater frequency. We also make several suggestions that we feel
      may help avoid the problems seen with this patient in the future.

PMID- 16998340
TI  - The glomangioma in the differential diagnosis of vascular malformations.
AB  - Glomus tumors develop from a thermoregulatory unit called the glomus body which
      is found in high density within the digits of both the hands and feet. To note,
      even though less frequently, these tumors can present in extradigital locations.
      Usually it presents as a small, 1-cm bluish nodule. Glomangioma (multiple glomus
      tumors) is to be differentiated clinically from the more solitary glomus tumor on
      the basis of larger size and prominent vascular markings. Although glomangioma is
      described in literature, the major textbooks of plastic surgery fail to mention
      it. A report of an unusual case of a large glomangioma in the shoulder of a 13
      year-old female is presented. Clinical picture, investigation, surgical
      treatment, and pathology of this lesion are discussed.

PMID- 16998341
TI  - Hair-thread tourniquet syndrome in an infant with bony erosion: a case report,
      literature review, and meta-analysis.
AB  - Hair-thread tourniquet syndrome is a rare condition where appendages are
      strangulated by an encircling strand of hair, a thread, or a fiber. The condition
      usually occurs in very young patients in the first few months of life. We present
      a unique case of a 3-month-old baby girl with hair-thread tourniquet syndrome in
      whom a hair cheese-wired through the skin and soft tissue of the toe and caused
      bony erosion of the underlying phalanx. An extensive literature review and meta
      analysis of the topic are also presented.

PMID- 16998342
TI  - Some selected dental and jaw aberrations.
AB  - There is a close but separate interrelationship between the development of the
      teeth and jaws. Some principles of the biology of teeth and jaws are central to
      this presentation. The basic blueprints of both the tooth and jaws are inherent.
      Postnatal growth is but a continuation of prenatal growth interrupted by the
      event of birth. In utero, the fetus with its genetic beginnings is subjected to
      the vicissitudes of the maternal environment. After birth, the individual is
      subjected to the effects of the general environment. Development of facial form
      is related to the synchronous coordination of 3-dimensional, multiple,
      differential dental and jaw growth sites and centers and associated structure
      activities. This report deals with some selected unusual dental and jaw
      aberrations, some of which may have developed during the prenatal period and
      others during infancy and early childhood. However, they may not become
      significantly clinically manifest sometimes until late childhood or even early
      adulthood. Dental histogenesis is correlated in several instances (anodontia,
      ameloblastoma, hemifacial, atrophy) with jaw implications. Thus, this article is
      a synthesis of previous reports in which many included surgical treatment.

PMID- 16998343
TI  - Luminal fillers in nerve conduits for peripheral nerve repair.
AB  - The use of nerve conduits as an alternative for nerve grafting has a long
      experimental and clinical history. Luminal fillers, factors introduced into these
      nerve conduits, were later developed to enhance the nerve regeneration through
      conduits. Though many luminal fillers have been reported to improve nerve
      regeneration, their use has not been subjected to systematic review. This review
      categorizes the types of fillers used, the conduits associated with fillers, and
      the reported performance of luminal fillers in conduits to present a preference
      list for the most effective fillers to use over specific distances of nerve
      defect.

PMID- 16998344
TI  - Socratic gender blending.

PMID- 16998346
TI  - Breast reduction as an alternative treatment option for early breast cancer in
      women with macromastia.

PMID- 16998347
TI  - Superficial lateral thoracic artery.

PMID- 16998349
TI  - Re: Donor-side selection in mandibular reconstruction using a free fibular
      osteocutaneous flap.

PMID- 16998351
TI  - Ultrasonography is more useful in assessment of suspected breast implant
      infections rather than capsular contracture.

PMID- 16998352
TI  - Correction of late post-traumatic enophthalmos using a tissue expander.

PMID- 16998353
TI  - An easy way to externalize the filling port of a tissue expander.

PMID- 16998354
TI  - Ear pain following prominent ear surgery: an observation.

PMID- 16998356
TI  - Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia
      repair: a multicenter, prospective, randomized trial.
AB  - OBJECTIVE: Laparoscopic paraesophageal hernia repair (LPEHR) is associated with a
      high recurrence rate. Repair with synthetic mesh lowers recurrence but can cause
      dysphagia and visceral erosions. This trial was designed to study the value of a
      biologic prosthesis, small intestinal submucosa (SIS), in LPEHR. METHODS:
      Patients undergoing LPEHR (n = 108) at 4 institutions were randomized to primary
      repair -1 degrees (n = 57) or primary repair buttressed with SIS (n = 51) using a
      standardized technique. The primary outcome measure was evidence of recurrent
      hernia (> or =2 cm) on UGI, read by a study radiologist blinded to the
      randomization status, 6 months after operation. RESULTS: At 6 months, 99 (93%)
      patients completed clinical symptomatic follow-up and 95 (90%) patients had an
      UGI. The groups had similar clinical presentations (symptom profile, quality of
      life, type and size of hernia, esophageal length, and BMI). Operative times (SIS
      202 minutes vs. 1 degrees 183 minutes, P = 0.15) and perioperative complications
      did not differ. There were no operations for recurrent hernia nor mesh-related
      complications. At 6 months, 4 patients (9%) developed a recurrent hernia >2 cm in
      the SIS group and 12 patients (24%) in the 1 degrees group (P = 0.04). Both
      groups experienced a significant reduction in all measured symptoms (heartburn,
      regurgitation, dysphagia, chest pain, early satiety, and postprandial pain) and
      improved QOL (SF-36) after operation. There was no difference between groups in
      either pre or postoperative symptom severity. Patients with a recurrent hernia
      had more chest pain (2.7 vs. 1.0, P = 0.03) and early satiety (2.8 vs. 1.3, P =
      0.02) and worse physical functioning (63 vs. 72, P = 0.03 per SF-36).
      CONCLUSIONS: Adding a biologic prosthesis during LPEHR reduces the likelihood of
      recurrence at 6 months, without mesh-related complications or side effects.

PMID- 16998357
TI  - The prevalence of distal and proximal gastroesophageal reflux in patients
      awaiting lung transplantation.
AB  - OBJECTIVE: To determine the prevalence and proximal extent of gastroesophageal
      reflux (GERD) in patients awaiting lung transplantation. BACKGROUND: GERD has
      been postulated to contribute to accelerated graft failure in patients who have
      had lung transplantations. However, the prevalence of reflux symptoms, esophageal
      motility abnormalities, and proximal esophageal reflux among patients with end
      stage lung disease awaiting lung transplantation are unknown. METHODS: A total of
      109 patients with end-stage lung disease awaiting lung transplantation underwent
      symptomatic assessment, esophageal manometry, and esophageal pH monitoring (using
      a probe with 2 sensors located 5 and 20 cm above the lower esophageal sphincter).
      RESULTS: Reflux symptoms were not predictive of the presence of reflux
      (sensitivity, 67%; specificity, 26%). Esophageal manometry showed a high
      prevalence of a hypotensive lower esophageal sphincter (55%) and impaired
      esophageal peristalsis (47%) among patients with reflux. Distal reflux was
      present in 68% of patients and proximal reflux was present in 37% of patients.
      CONCLUSIONS: These data show that in patients with end-stage lung disease: 1)
      symptoms were insensitive and nonspecific for diagnosing reflux; 2) esophageal
      motility was frequently abnormal; 3) 68% of patients had GERD; 4) in 50% of the
      patients with GERD, acid refluxed into the proximal esophagus. We conclude that
      patients with end-stage lung disease should be screened with pH monitoring for
      GERD.

PMID- 16998358
TI  - An acute care surgery model improves outcomes in patients with appendicitis.
AB  - OBJECTIVE: To compare outcomes of appendectomy in an Acute Care Surgery (ACS)
      model to that of a traditional home-call attending surgeon model. SUMMARY
      BACKGROUND DATA: Acute care surgery (ACS, a combination of trauma surgery,
      emergency surgery, and surgical critical care) has been proposed as a practice
      model for the future of general surgery. To date, there are few data regarding
      outcomes of surgical emergencies in the ACS model. METHODS: Between September
      1999 and August 2002, surgical emergencies were staffed at the faculty level by
      either an in-house trauma/emergency surgeon (ACS model) or a non-trauma general
      surgeon taking home call (traditional [TRAD] model). Coverage alternated monthly.
      Other aspects of hospital care, including resident complement, remained
      unchanged. We retrospectively reviewed key time intervals (emergency department
      [ED] presentation to surgical consultation; surgical consultation to operation
      [OR]; and ED presentation to OR) and outcomes (rupture rate, negative
      appendectomy rate, complication rate, and hospital length of stay [LOS]) for
      patients treated in the ACS and TRAD models. Questions of interest were examined
      using chi tests for discrete variables and independent sample t test for
      comparison of means. RESULTS: During the study period, 294 appendectomies were
      performed. In-house ACS surgeons performed 167 procedures, and the home-call TRAD
      surgeons performed 127 procedures. No difference was found in the time from ED
      presentation to surgical consultation; however, the time interval from
      consultation to OR was significantly decreased in the ACS model (TRAD 7.6 hours
      vs. ACS 3.5 hours, P < 0.05). As a result, the total time from ED presentation to
      OR was significantly shorter in the ACS model (TRAD 14.0 hours vs. ACS 10.1 hour,
      P < 0.05). Rupture rates were decreased in the ACS model (TRAD 23.3% vs. ACS
      12.3%, P < 0.05); negative appendectomy rates were similar. The complication rate
      in the ACS model was decreased (TRAD 17.4% vs. ACS 7.7%, P < 0.05), as was the
      hospital LOS (TRAD 3.5 days vs. ACS 2.3 days, P < 0.001). CONCLUSIONS: In
      patients with acute appendicitis, the presence of an in-house acute care surgeon
      significantly decreased the time to operation, rupture rate, complication rate,
      and hospital length of stay. The ACS model appears to improve outcomes of acute
      appendicitis compared with a TRAD home-call model. This study supports the
      efficacy and efficiency of the ACS model in the management of surgical
      emergencies.

PMID- 16998359
TI  - Treatment evolution in high-risk congenital diaphragmatic hernia: ten years'
      experience with diaphragmatic agenesis.
AB  - OBJECTIVE: The objective of this study was to evaluate the impact of newer
      therapies on the highest risk patients with congenital diaphragmatic hernia
      (CDH), those with agenesis of the diaphragm. SUMMARY BACKGROUND DATA: CDH remains
      a significant cause of neonatal mortality. Many novel therapeutic interventions
      have been used in these infants. Those children with large defects or agenesis of
      the diaphragm have the highest mortality and morbidity. METHODS: Twenty centers
      from 5 countries collected data prospectively on all liveborn infants with CDH
      over a 10-year period. The treatment and outcomes in these patients were
      examined. Patients were followed until death or hospital discharge. RESULTS: A
      total of 1,569 patients with CDH were seen between January 1995 and December 2004
      in 20 centers. A total of 218 patients (14%) had diaphragmatic agenesis and
      underwent repair. The overall survival for all patients was 68%, while survival
      was 54% in patients with agenesis. When patients with diaphragmatic agenesis from
      the first 2 years were compared with similar patients from the last 2 years,
      there was significantly less use of ECMO (75% vs. 52%) and an increased use of
      inhaled nitric oxide (iNO) (30% vs. 80%). There was a trend toward improved
      survival in patients with agenesis from 47% in the first 2 years to 59% in the
      last 2 years. The survivors with diaphragmatic agenesis had prolonged hospital
      stays compared with patients without agenesis (median, 68 vs. 30 days). For the
      last 2 years of the study, 36% of the patients with agenesis were discharged on
      tube feedings and 22% on oxygen therapy. CONCLUSIONS: There has been a change in
      the management of infants with CDH with less frequent use of ECMO and a greater
      use of iNO in high-risk patients with a potential improvement in survival.
      However, the mortality, hospital length of stay, and morbidity in agenesis
      patients remain significant.

PMID- 16998360
TI  - Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses
      protective Th1 immunity.
AB  - OBJECTIVES: We recently reported increased CD4 CD25 T regulatory (Treg) activity
      after burn injury in mice. This study sought to determine if Tregs mediate the
      reduction in TH1-type immunity after serious injury in man and if Treg function
      is altered by injury. METHODS: Peripheral blood was withdrawn from 19 consenting
      adult patients (35.1 +/- 16.3 years of age) with Injury Severity Scores (ISS)
      36.6 +/- 13.9 on days 1 and 7 after trauma and from 5 healthy individuals. CD4 T
      cells were purified and sorted into Treg (CD25(high)) and Treg-depleted
      populations. After activation of cells with anti-CD3/CD28 antibody, production of
      the TH1-type cytokine IFNgamma, TH2-type cytokines (IL-4 and IL-5), and the
      inhibitory cytokine IL-10 was measured using cytometric bead arrays. Treg
      activity was measured by in vitro suppression of autologous CD4 T cell
      proliferation. RESULTS: All patients survived, 9 (47%) developed infection
      postinjury. IFNgamma production by patient CD4 T cells was decreased on day 1 and
      day 7, when compared with healthy controls. However, when Tregs were depleted
      from the CD4 T cells, the IFNgamma production increased to control levels. Tregs
      were the chief source of IL-4 and IL-5 as well as IL-10. Treg suppression of T
      cell proliferation increased significantly from day 1 to day 7 after injury.
      CONCLUSIONS: We demonstrate for the first time that human Tregs are increased in
      potency after severe injury. Most significantly, Tregs are important mediators of
      the suppression of T cell activation and the reduction in TH1 cytokine production
      found after injury.

PMID- 16998361
TI  - Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of
      1,452 patients and development of a prognostic model.
AB  - OBJECTIVE: To determine the utility of hepatic resection (HR) in the treatment of
      patients with noncolorectal nonendocrine liver metastases (NCNELM). SUMMARY
      BACKGROUND DATA: The place of HR in the treatment of NCNELM remains
      controversial, primarily due to the limitations of previously published reports
      and the heterogeneity of primary tumor sites and histologies. METHODS: A
      multivariate risk model was developed by analyzing prognostic factors and long
      term outcomes in 1452 patients with NCNELM treated with HR at 41 centers from
      1983 to 2004. RESULTS: Hepatic metastases were solitary in 56% and unilateral in
      71% (mean diameter, 50.5 mm). Extrahepatic metastases were present in 22%. The
      most common primary sites were breast (32%), gastrointestinal (16%), and urologic
      (14%). The most common histologies were adenocarcinoma (60%), GIST/sarcoma
      (13.5%), and melanoma (13%). R0 resection was achieved in 83% of patients with a
      60-day mortality rate of 2.3% and a major complication rate of 21.5%. Tumor
      recurred in 67% of patients (liver, 24%; extrahepatic, 18%; both, 25%). Overall
      and disease-free survivals at 5 years were 36% and 21% and at 10 years were 23%
      and 15%, respectively. In multivariate analysis, factors associated with poor
      prognosis were patient age >60 years, nonbreast origin, melanoma or squamous
      histology, disease-free interval <12 months, extrahepatic metastases, R2
      resection, and major hepatectomy (all P < or = 0.02). A prognostic model based on
      these factors effectively stratified patients into low-risk (0-3 points, 46% 5
      year survival), mid-risk (4-6 points, 33% 5-year survival), and high-risk (>6
      points, <10% 5-year survival) groups (P = 0.0001). DISCUSSION: HR for NCNELM is
      safe and effective, with outcomes mainly dependent on primary tumor site and
      histology. For individual patients, a statistical model based on key prognostic
      factors could validate the indication for hepatic resection by predicting long
      term survivals.

PMID- 16998362
TI  - The effect of insulin infusion upon protein metabolism in neonates on
      extracorporeal life support.
AB  - OBJECTIVE: Critically ill neonates on extracorporeal life support (ECLS)
      demonstrate elevated rates of protein breakdown that, in turn, are associated
      with increased morbidity and mortality. This study sought to determine if the
      administration of the anabolic hormone insulin improved net protein balance in
      neonates on ECLS. METHODS: Twelve parenterally fed neonates, on ECLS, were
      enrolled in a randomized, prospective, crossover trial. Subjects were
      administered a hyperinsulinemic euglycemic clamp and a control saline infusion.
      Protein metabolism was quantified using ring-D5-phenylyalanine and ring-D2
      tyrosine stable isotopic infusions. Statistical comparisons were made by paired
      sample t tests (significance at P < 0.05). RESULTS: Serum insulin concentration
      increased 20-fold during insulin infusion compared with saline infusion control
      (P < 0.0001). Protein breakdown was significantly decreased during insulin
      infusion compared with controls (7.98 +/- 1.82 vs. 6.89 +/- 1.03 g/kg per day; P
      < 0.05). Serum amino acid concentrations were significantly decreased by insulin
      infusion (28,450 +/- 9270 vs. 20,830 +/- 8110 micromol/L; P < 0.02). Insulin
      administration tended to decrease protein synthesis (9.58 +/- 2.10 g/kg per day
      vs. 8.60 +/- 1.20; P = 0.05). For the whole cohort, insulin only slightly
      improved net protein balance (protein synthesis minus protein breakdown) (1.60 +/
      0.80 vs. 1.71 +/- 0.89 g/kg per day; P = 0.08). In neonates receiving > or =2
      g/kg per day of dietary amino acids insulin significantly improved net protein
      balance (2.17 +/- 0.34 vs. 2.40 +/- 0.26 g/kg per day; P < 0.01). CONCLUSIONS:
      Insulin effectively decreases protein breakdown in critically ill neonates on
      ECLS. However, this is associated with a significant reduction in plasma amino
      acids and a trend toward decreased protein synthesis. Insulin administration
      significantly improves net protein balance only in those ECLS neonates in whom
      adequate dietary protein is provided.

PMID- 16998363
TI  - The impact of an intensivist-model ICU on trauma-related mortality.
AB  - OBJECTIVE: To evaluate the effect of an intensivist-model of critical care
      delivery on the risk of death following injury. SUMMARY BACKGROUND DATA: An
      intensivist-model of ICU care is associated with improved outcomes and less
      resource utilization in mixed medical and surgical ICUs. The process of trauma
      center verification assures a relatively high standard of care and quality
      assurance; thus, it is unclear what the effect of a specific model of ICU care
      delivery might have on trauma-related mortality. METHODS: Using data from a large
      multicenter (68 centers) prospective cohort study, we evaluated the relationship
      between the model of ICU care (open vs. intensivist-model) and in-hospital
      mortality following severe injury. An intensivist-model was defined as an ICU
      where critically ill trauma patients were either on a distinct ICU service (led
      by an intensivist) or were comanaged with an intensivist (a physician board
      certified in critical care). RESULTS: After adjusting for differences in baseline
      characteristics, the relative risk of death in intensivist-model ICUs was 0.78
      (0.58-1.04) compared with an open ICU model. The effect was greatest in the
      elderly [RR, 0.55 (0.39-0.77)], in units led by surgical intensivists [RR, 0.67
      (0.50-0.90)], and in designated trauma centers 0.64 (0.46-0.88). CONCLUSIONS:
      Care in an intensivist-model ICU is associated with a large reduction in in
      hospital mortality following trauma, particularly in elderly patients who might
      have limited physiologic reserve and extensive comorbidity. That the effect is
      greatest in trauma centers and in units led by surgical intensivists suggests the
      importance of content expertise in the care of the critically injured. Injured
      patients are best cared for using an intensivist-model of dedicated critical care
      delivery, a criterion that should be considered in the verification of trauma
      centers.

PMID- 16998364
TI  - Donation after cardiac death as a strategy to increase deceased donor liver
      availability.
AB  - OBJECTIVE: This study examines donation after cardiac death (DCD) practices and
      outcomes in liver transplantation. SUMMARY BACKGROUND DATA: Livers procured from
      DCD donors have recently been used to increase the number of deceased donors and
      bridge the gap between limited organ supply and the pool of waiting list
      candidates. Comprehensive evaluation of this practice and its outcomes has not
      been previously reported. METHODS: A national cohort of all DCD and donation
      after brain-death (DBD) liver transplants between January 1, 2000 and December
      31, 2004 was identified in the Scientific Registry of Transplant Recipients. Time
      to graft failure (including death) was modeled by Cox regression, adjusted for
      relevant donor and recipient characteristics. RESULTS: DCD livers were used for
      472 (2%) of 24,070 transplants. Annual DCD liver activity increased from 39 in
      2000 to 176 in 2004. The adjusted relative risk of DCD graft failure was 85%
      higher than for DBD grafts (relative risk, 1.85; 95% confidence interval, 1.51
      2.26; P < 0.001), corresponding to 3-month, 1-year, and 3-year graft survival
      rates of 83.0%, 70.1%, and 60.5%, respectively (vs. 89.2%, 83.0%, and 75.0% for
      DBD recipients). There was no significant association between transplant program
      DCD liver transplant volume and graft outcome. CONCLUSIONS: The annual number of
      DCD livers used for transplant has increased rapidly. However, DCD livers are
      associated with a significantly increased risk of graft failure unrelated to
      modifiable donor or recipient factors. Appropriate recipients for DCD livers have
      not been fully characterized and recipient informed consent should be obtained
      before use of these organs.

PMID- 16998365
TI  - Effect of nonviral factors on hepatitis C recurrence after liver transplantation.
AB  - OBJECTIVE: Hepatitis C (HCV) is now the most common indication for orthotopic
      liver transplantation (OLT). While graft reinfection remains universal,
      progression to graft cirrhosis is highly variable. This study examined donor,
      recipient, and operative variables to identify factors that affect recurrence of
      HCV post-OLT to facilitate graft-recipient matching. METHODS: Retrospective
      review of 307 patients who underwent OLT for HCV over a 10-year period at our
      center. Recurrence of HCV was identified by the presence of biochemical graft
      dysfunction and concurrent liver biopsy showing diagnostic pathologic features.
      Time to recurrence was the endpoint for statistical analysis. Five donor, 6
      recipient, and 2 operative variables that may affect recurrence were analyzed by
      univariate comparison and Cox proportional hazard regression models. RESULTS:
      Recurrence-free survival in the 307 study patients was 69% and 34% at 1 and 5
      years, respectively. Four predictive variables related to either donor or
      recipient characteristics were identified. Advanced donor age, prolonged donor
      hospitalization, increasing recipient age, and elevated recipient MELD scores
      were found to increase the relative risk of HCV recurrence. Examination of HLA
      disparity between donors and recipients demonstrated no correlation between class
      I or class II mismatches and recurrence-free survival. CONCLUSIONS: We have
      identified donor and recipient characteristics that significantly predict
      hepatitis C recurrence following liver transplantation. These factors are
      identifiable before transplant and, if considered when matching donors to HCV
      recipients, may decrease the incidence of HCV recurrence after OLT. A change in
      the current national liver allocation system would be needed to realize the full
      value of this benefit.

PMID- 16998366
TI  - A selective approach to the resection of cystic lesions of the pancreas: results
      from 539 consecutive patients.
AB  - OBJECTIVE: To define a group of patients with pancreatic cysts who do not require
      resection. SUMMARY BACKGROUND DATA: The increased use of cross-sectional imaging
      has resulted in an increased identification of small, asymptomatic pancreatic
      cysts. Data have not been available to determine which lesions should be
      resected. METHODS: All patients evaluated at our institution between January 1995
      and January 2005 for the ICD-9 diagnosis of pancreatic cyst were reviewed.
      Analysis was performed to identify associations between patient and cyst
      characteristics, and selection of operative or nonoperative management. RESULTS:
      Pancreatic cysts were evaluated in 539 patients. Initial management was operative
      in 170 patients (32%), and nonoperative (radiographic follow-up) in 369 patients
      (68%). Factors associated with initial operative management included presence of
      a solid component (45% vs. 6%, P < 0.001), larger size of the lesion (mean 4.8 cm
      vs. 2.4 cm, P = 0.001), and presence of symptoms (44% vs. 16%, P = 0.001).
      Malignancy was present in 18% (32 of 170) of patients initially resected.
      Mucinous tumors (n = 18) were the most common malignant histologic subtype. None
      of the invasive cancers arising from mucinous cysts was <3 cm. Median
      radiographic follow-up in patients initially managed nonoperatively was 24 months
      (range, 1-172 months). In 29 patients (8%), changes developed within the cyst
      that resulted in resection; malignancy was present in 11 of 39 (38%),
      representing 3% (11 of 369) of all patients being followed radiographically.
      CONCLUSIONS: Selected patients with cystic lesions <3 cm in diameter and without
      a solid component may be followed radiographically with a malignancy risk (3%
      this study) that approximates the risk of mortality from resection. Malignancy
      within mucinous tumors is associated with size, and small mucinous tumors are
      very unlikely to be malignant.

PMID- 16998367
TI  - A new era in the surgical treatment of atrial fibrillation: the impact of
      ablation technology and lesion set on procedural efficacy.
AB  - BACKGROUND/OBJECTIVE: While the Cox-Maze procedure remains the gold standard for
      the surgical treatment of atrial fibrillation (AF), the use of ablation
      technology has revolutionized the field. To simplify the procedure, our group has
      replaced most of the incisions with bipolar radiofrequency ablation lines. The
      purpose of this study was to examine results using bipolar radiofrequency in 130
      patients undergoing a full Cox-Maze procedure, a limited Cox-Maze procedure, or
      pulmonary vein isolation alone. METHODS: A retrospective review was performed of
      patients who underwent a Cox-Maze procedure (n = 100), utilizing bipolar
      radiofrequency ablation, a limited Cox-Maze procedure (n = 7), or pulmonary vein
      isolation alone (n = 23). Follow-up was available on 129 of 130 patients (99%).
      RESULTS: Pulmonary vein isolation was confirmed by intraoperative pacing in all
      patients. Cross-clamp time in the lone Cox-Maze procedure patients was 44 +/- 21
      minutes, and 104 +/- 42 minutes for the Cox-Maze procedure with a concomitant
      procedure, which was shortened considerably from our traditional cut-and-sew Cox
      Maze procedure times (P < 0.05). There were 4 postoperative deaths in the Cox
      Maze procedure group and 1 in the pulmonary vein isolation group. The mean follow
      up was 13 +/- 10, 23 +/- 15, and 9 +/- 10 months for the Cox-Maze IV, the
      pulmonary vein isolation, and the limited Cox-Maze procedure groups,
      respectively. At last follow-up, freedom from AF was 90% (85 of 94), 86% (6 of
      7), and 59% (10 of 17) in the in the Cox-Maze procedure group, limited Cox-Maze
      procedure group, and pulmonary vein isolation alone group, respectively.
      CONCLUSIONS: The use of bipolar radiofrequency ablation to replace Cox-Maze
      incisions was safe and effective at controlling AF. Pulmonary vein isolation
      alone was much less effective, and should be used cautiously in this population.

PMID- 16998368
TI  - Serologic markers of brain injury and cognitive function after cardiopulmonary
      bypass.
AB  - OBJECTIVE: To examine the association between biochemical markers of brain injury
      (MBI) and the inflammatory response in relation to neurocognitive deficiency
      (NCD) after cardiopulmonary bypass (CPB). SUMMARY BACKGROUND DATA: In cardiac
      surgery, NCD is a common but underdiagnosed complication with an unclear
      pathophysiology leading to significant morbidity. Despite extensive
      investigation, identification of a MBI for clinical use and clarifying the
      pathophysiology of NCD have not been achieved. METHODS: Forty patients undergoing
      CABG and/or valve procedures using CPB were administered a validated
      neurocognitive battery preoperatively and postoperatively at day 4 and 3 months.
      S-100b, neuron specific enolase (NSE), and tau protein were assayed as MBIs
      preoperatively and postoperatively at 6 hours and day 4. C-reactive protein
      (CRP), interleukin (IL)-6, C3a, and total peroxide levels were also quantified
      from serum. Impact of cardiotomy suction and antifibrinolytics on markers of
      brain injury was assessed. RESULTS: The incidence of early NCD was 40% (16 of
      40). NSE and tau protein at the 6-hour time point were both significantly
      elevated in the presence of NCD (NCD group) compared with those without NCD (NORM
      group) (8.69 +/- 0.82 vs. 5.98 +/- 0.61; P = 0.018 and 68.8 vs. 29.2%; P = 0.015;
      respectively). S-100b increase was not different between the NCD and NORM groups.
      Cardiotomy suction significantly elevated S-100b levels, whereas NSE and tau were
      not significantly influenced. Aprotinin did not have an effect on NCD or levels
      of MBIs. Also, the NCD group had significantly elevated CRP and peroxide levels
      compared with the NORM group at postoperative day 4 while C3a was significantly
      elevated at 6 hours. CONCLUSION: NSE and tau are better associated with NCD and
      less influenced by cardiotomy suction compared with S-100beta. Inflammatory and
      oxidative stress is associated with NCD post-CPB.

PMID- 16998369
TI  - More extensive nodal dissection improves survival for stages I to III of colon
      cancer: a population-based study.
AB  - OBJECTIVE: To determine whether analyzing more lymph nodes in colon cancer
      specimens improves survival. SUMMARY BACKGROUND DATA: Increasing the number of
      lymph nodes analyzed has been reported to correlate with improved survival in
      patients with node-negative colon cancer. METHODS: The Surveillance,
      Epidemiology, and End Results database was queried for all patients undergoing
      resection for histologically confirmed colon cancer between the years 1988 and
      2000. Patients were excluded for distant metastases or if an unknown number of
      nodes was sampled. The number of nodes sampled was categorized into 0, 1 to 7, 8
      to 14, and > or =15 nodes. Survival curves constructed using the Kaplan-Meier
      method were compared using log rank testing. A Cox proportional hazard model was
      created to adjust for year of diagnosis, age, race, gender, tumor grade, tumor
      size, TNM stage, and percent of nodes positive for tumor. RESULTS: The median
      number of lymph nodes sampled for all 82,896 patients was 9. For all stages
      examined, increasing nodal sampling was associated with improved survival.
      Multivariate regression demonstrated that patients who had at least 15 nodes
      sampled as compared with 1 to 7 nodes experienced a 20.6% reduction in mortality
      independent of other patient and tumor characteristics. CONCLUSIONS: Adequate
      lymphadenectomy, as measured by analysis of at least 15 lymph nodes, correlates
      with improved survival, independent of stage, patient demographics, and tumor
      characteristics. Currently, most procedures do not meet this guideline. Future
      trials of adjuvant therapy should include extent of lymphadenectomy as a
      stratification factor.

PMID- 16998370
TI  - Duodenal switch provides superior weight loss in the super-obese (BMI > or =50
      kg/m2) compared with gastric bypass.
AB  - OBJECTIVES: Although weight loss following Roux-en-Y gastric bypass is acceptable
      in patients with preoperative body mass index (BMI) between 35 and 50 kg/m,
      results from several series demonstrate that failure rates approach 40% when BMI
      is > or =50 kg/m. Here we report the first large single institution series
      directly comparing weight-loss outcomes in super-obese patients following
      biliopancreatic diversion with duodenal switch (DS) and Roux-en-Y Gastric Bypass
      (RYGB). METHODS: All super-obese patients (BMI > or =50 kg/m) undergoing
      standardized laparoscopic and open DS and RYGB between August 2002 and October
      2005 were identified from a prospective database. Two-sample t tests were used to
      compare weight loss, decrease in BMI, and percentage of excess body weight loss
      (% EBWL) after surgery. chi analysis was used to determine the rate of successful
      weight loss, defined as achieving at least 50% loss of excess body weight.
      RESULTS: A total of 350 super-obese patients underwent DS (n = 198) or RYGB (n =
      152) with equal 30-day mortality (DS,1 of 198; RYGB, 0 of 152; P = not
      significant). The % EBWL at follow-up was greater for DS than RY (12 months,
      64.1% vs. 55.9%; 18 months, 71. 9% vs. 62.8%; 24 months, 71.6% vs. 60.1%; 36
      months, 68.9% vs. 54.9%; P < 0.05). Total weight loss and decrease in BMI were
      also statistically greater for the DS (data not shown). Importantly, the
      likelihood of successful weight loss (EBWL >50%) was significantly greater in
      patients following DS (12 months, 83.9% vs. 70.4%; 18 months, 90.3% vs. 75.9%; 36
      months, 84.2% vs. 59.3%; P < 0.05). CONCLUSIONS: Direct comparison of DS to RYGB
      demonstrates superior weight loss outcomes for DS.

PMID- 16998371
TI  - Selective nonoperative management of penetrating abdominal solid organ injuries.
AB  - OBJECTIVE: To assess the feasibility and safety of selective nonoperative
      management in penetrating abdominal solid organ injuries. BACKGROUND:
      Nonoperative management of blunt abdominal solid organ injuries has become the
      standard of care. However, routine surgical exploration remains the standard
      practice for all penetrating solid organ injuries. The present study examines the
      role of nonoperative management in selected patients with penetrating injuries to
      abdominal solid organs. PATIENTS AND METHODS: Prospective, protocol-driven study,
      which included all penetrating abdominal solid organ (liver, spleen, kidney)
      injuries admitted to a level I trauma center, over a 20-month period. Patients
      with hemodynamic instability, peritonitis, or an unevaluable abdomen underwent an
      immediate laparotomy. Patients who were hemodynamically stable and had no signs
      of peritonitis were selected for further CT scan evaluation. In the absence of CT
      scan findings suggestive of hollow viscus injury, the patients were observed with
      serial clinical examinations, hemoglobin levels, and white cell counts. Patients
      with left thoracoabdominal injuries underwent elective laparoscopy to rule out
      diaphragmatic injury. Outcome parameters included survival, complications, need
      for delayed laparotomy in observed patients, and length of hospital stay.
      RESULTS: During the study period, there were 152 patients with 185 penetrating
      solid organ injuries. Gunshot wounds accounted for 70.4% and stab wounds for
      29.6% of injuries. Ninety-one patients (59.9%) met the criteria for immediate
      operation. The remaining 61 (40.1%) patients were selected for CT scan
      evaluation. Forty-three patients (28.3% of all patients) with 47 solid organ
      injuries who had no CT scan findings suspicious of hollow viscus injury were
      selected for clinical observation and additional laparoscopy in 2. Four patients
      with a "blush" on CT scan underwent angiographic embolization of the liver.
      Overall, 41 patients (27.0%), including 18 cases with grade III to V injuries,
      were successfully managed without a laparotomy and without any abdominal
      complication. Overall, 28.4% of all liver, 14.9% of kidney, and 3.5% of splenic
      injuries were successfully managed nonoperatively. Patients with isolated solid
      organ injuries treated nonoperatively had a significantly shorter hospital stay
      than patients treated operatively, even though the former group had more severe
      injuries. In 3 patients with failed nonoperative management and delayed
      laparotomy, there were no complications. CONCLUSIONS: In the appropriate
      environment, selective nonoperative management of penetrating abdominal solid
      organ injuries has a high success rate and a low complication rate.

PMID- 16998373
TI  - Fatal and nonfatal hemorrhagic complications of living kidney donation.

PMID- 16998374
TI  - Possible Intergel Reaction Syndrome (pIRS).

PMID- 16998375
TI  - Surgical management of complications associated with percutaneous and/or
      endoscopic management of pseudocyst of the pancreas.

PMID- 16998376
TI  - Peritoneal carcinomatosis of colorectal origin: standard of care.

PMID- 16998378
TI  - The study of cavitational ultrasonically aspirated material during surgery for
      colorectal liver metastases as a new concept in resection margin.

PMID- 16998379
TI  - Predictive indices of morbidity and mortality after liver resection.

PMID- 16998380
TI  - Predictive indices of morbidity and mortality after liver resection.

PMID- 16998381
TI  - Evidence-based treatment of acute pancreatitis: antibiotic prophylaxis in
      necrotizing pancreatitis.

PMID- 16998384
TI  - Burn centers and disaster response.

PMID- 16998386
TI  - Gastrointestinal fluid resuscitation of thermally injured patients.

PMID- 16998387
TI  - Triage accuracy at a multiple casualty incident disaster drill: the Emergency
      Medical Service, Fire Department of New York City experience.
AB  - We sought to evaluate the accuracy and speed for the triage of multiple patients
      during a disaster drill by Emergency Medical Service (EMS) personnel. During a
      disaster drill (train collision with blast injury and chemical release), the
      accuracy and speed of triage of 130 patient-actors by the Fire Department of New
      York City (FDNY) EMS personnel was evaluated using the Simple Triage and Rapid
      Treatment (START) triage system. All EMS personnel had been previously trained in
      START, but refresher training was not administered before the drill. Overall
      triage accuracy was 78%. In patients that had additional changes in their status
      during the triage process (injects), 62% were retriaged appropriately. Because of
      security and decontamination procedures, triage at the triage/treatment area
      began 40 minutes after the drill commenced. It took 2 hours and 38 minutes to
      completely clear the scene of all patients. On average, the time from the start
      of triage to transport was 1 hour and 2 minutes. Despite the fact that triage is
      a skill practiced by every EMS system in the country on a daily basis, few
      studies regarding triage accuracy are available. Limited data suggest that the
      triage accuracy rates using different triage strategy algorithms are
      approximately 45% to 55%. During this drill, FDNY-EMS triage accuracy using the
      START system exceeded these expectations. This study provides insight as to the
      triage experience of a large urban EMS system operating at a disaster drill.

PMID- 16998388
TI  - Terrorist homicide bombings: a primer for preparation.
AB  - Contemporary planning for disaster response to terrorist events usually assumes
      the use of chemical, radiological, or biological weapons. Historically, most
      victims of terrorist attacks are injured by the use of conventional explosives
      rather than weapons of mass destruction. Such attacks will likely produce victims
      who have suffered burn injuries along with conventional trauma. Alternately, the
      large number of patients sustaining conventional soft-tissue or crush injuries
      will benefit from burn center expertise. This study summarizes the current state
      of knowledge related to the management of terrorism mass casualty incidents
      caused by the use of conventional explosives. A review of pertinent medical,
      technical, and popular literature relating to terrorism and explosives, along
      with instruction received at Hadassah Hospital, Jerusalem, Israel on the
      management of mass casualty terrorism events was undertaken, and the pertinent
      medical and scientific literature relating to bomb delivery methods, blast
      mechanics, blast pathophysiology, and medical response to a terrorist bombing is
      presented here. Although terrorist use of chemical, radiological, or biological
      weapons is possible, historical analysis consistently demonstrates that the most
      likely terrorist weapon causing a mass casualty event is a standard explosive
      device detonated in a crowded area. The medical basis for management of such
      casualties is herein described.

PMID- 16998389
TI  - The Southern Region burn disaster plan.
AB  - A regional burn disaster plan for 24 burn centers located in 11 states comprising
      the Southern Region of the American Burn Association was developed using online
      and in-person collaboration between burn center directors during a 2-year period.
      The capabilities and preferences of burn centers in the Southern Region were
      queried. A website with disaster information, including a map of regional burn
      centers and spreadsheet of driving distances between centers, was developed.
      Standard terminology for burn center capabilities during disasters was defined as
      open, full, diverting, offloading, or returning. A simple, scalable, and flexible
      disaster plan was designed. Activation and escalation of the plan revolves around
      the requirements of the end user, the individual burn center director. A key
      provision is the designation of a central communications point colocated at a
      burn center with several experienced burn surgeons. In a burn disaster, the burn
      center director can make a single phone call to the communications center, where
      a senior burn surgeon remote from the disaster can contact other burn centers and
      emergency agencies to arrange assistance. Available options include diversion of
      new admissions to the next closest center, transfer of patients to other regional
      centers, or facilitation of activation of federal plans to bring burn care
      providers to the affected burn center. Cooperation between regional burn center
      directors has produced a simple and flexible regional disaster plan at minimal
      cost to institute or operate.

PMID- 16998390
TI  - Can burn centers evacuate in response to disasters?
AB  - On August 29, 2005, the Gulf Coast was hit by Hurricane Katrina, a category 4
      storm. The storm was responsible for more than 1000 deaths and the displacement
      of hundreds of thousands of people. Hospitals in the city of New Orleans
      evacuated because of the complete collapse of infrastructure. This event
      influenced the decisions and actions taken to protect patients, families, and
      staff of a 30-bed pediatric burn center in the projected path of a second
      catastrophic hurricane 3 weeks later. Approximately 80 hours before projected
      landfall, the local government announced that a mandatory evacuation of the
      community surrounding the burn center would occur. A coordinated decision was
      made by administration, nursing, and medical staff to cancel upcoming clinics and
      elective surgery and to evacuate all 14 inpatients, 52 outpatients, and 66
      guardians to other facilities. The evacuation plan was successfully completed in
      32 hours. The eye wall of the hurricane passed 65 miles east of the burn center.
      No significant damage to the physical plant was noted. Repopulation of the
      hospital by patients and acceptance of new acute burn referrals began
      approximately 40 hours after the local government permitted the population to
      return to the area. No morbidity or mortality was attributed to the evacuation.
      Emergent evacuation of threatened burn centers can be safely accomplished with
      adequate prior planning of evacuation sites, and modes of transportation. An
      established communication command center plays a key role in this process.

PMID- 16998391
TI  - Psychiatric sequelae of disasters.
AB  - In addition to physical injuries, survivors of disasters also suffer
      psychological trauma. Resulting mental anguish and illness can be profoundly
      debilitating and complicate the recovery and rehabilitation process. Front-line
      trauma teams caring for survivors of disasters must know the risks, assessment,
      and appropriate response to psychological injury. This article reviews the
      development of understanding mental disturbance after disasters and current
      approaches to evaluation and treatment.

PMID- 16998392
TI  - Evolution of burn resuscitation in operation Iraqi freedom.

PMID- 16998393
TI  - Contemplating the Pentagon attack after five years of space and time: unheard
      voices from the ramparts of our burn center.
AB  - Marking the fifth year after the attack on the Pentagon, staff at the burn center
      in Washington, DC, memorialize in a contemplative frame of mind. These
      reflections are drawn from members of the extended burn team and render an
      interwoven sketch in prose that previously has not been heard.

PMID- 16998394
TI  - Planning for burn disasters: lessons learned from one hundred years of history.
AB  - The terrorist attacks of September 11th have prompted interest in developing
      plans to manage thousands of burn casualties. There is little actual experience
      in the United States in managing disasters of this magnitude. As an alternative,
      lessons may be learned from the historical experiences of previous civilian burn
      or fire disasters occurring in this country. A review of relevant medical, fire
      service, and popular literature pertaining to civilian burn or fire disasters
      occurring in the United States between the years 1900 and 2000 was performed. In
      the 20th century, 73 major U.S. fire or burn disasters have occurred. With each
      disaster prompting a strengthening of fire regulations or building codes, the
      number of fatalities per incident has steadily decreased. Detailed examination of
      several landmark fires demonstrated that casualty counts were great but that most
      victims had fatal injuries and died on the scene or within 24 hours. A second
      large cohort comprised the walking wounded, who required minimal outpatient
      treatment. Patients requiring inpatient burn care comprise a small percentage of
      the total casualty figure but consume enormous resources during hospitalization.
      Burn mass casualty incidents are uncommon. The number of casualties per incident
      decreased over time. In most fire disasters, the majority of victims either
      rapidly die or have minimal injuries and can be treated and released. As a
      result, most disasters produce fewer than 25 to 50 patients requiring inpatient
      burn care. This would be a rational point to begin burn center preparations for
      mass casualty incidents. A robust outpatient capability to manage the walking
      wounded is also desirable.

PMID- 16998395
TI  - Burn-injured patients in a disaster: September 11th revisited.
AB  - We sought to review the steps taken by the New York Presbyterian Healthcare
      System to address disaster preparedness in the wake of the terrorist attacks of
      September 11, 2001. We reviewed the institutional records of emergency
      preparedness efforts, including improvements in infrastructure, employee
      education and training, and participation in intramural and extramural disaster
      response initiatives. We used a state discharge database to review burn injury
      triage within New York State (1995-2004). Since September 11, 2001, significant
      resources have been devoted to emergency preparedness: expansion of emergency
      services training, education, response, equipment, and communications;
      participation in regional disaster response exercises; revision of hospital
      preparedness plans; and development of municipal and regional responses to a burn
      mass casualty incident. A review of state and city burn triage patterns during
      the period of 1995 to 2004 revealed a decline in the number of burn cases treated
      in New York State-based hospitals by an average of 81 +/- 24 (mean +/- SEM) fewer
      cases/year (P = .01), occurring primarily in hospitals outside of New York City.
      Additionally, there was a steady increase in the proportion of New York City burn
      patients treated at burn center hospitals by 1.8 +/- 0.1 % per year (P < .0001).
      In response to the events of September 11, 2001, this health care system and this
      hospital has taken many steps to enhance its disaster response capabilities.

PMID- 16998396
TI  - Airplane crash in Guam, August 6, 1997: the aeromedical evacuation response.
AB  - A civilian airplane crash on the island of Guam in 1997 produced 16 burned
      survivors. The U.S. Army Burn Flight Team and U.S. Air Force Critical Care Air
      Transport Teams conducted a joint aeromedical mission in response to this
      disaster. This experience was reviewed from the Burn Flight Team perspective. A
      record of events was made during the mission, and an after-action review was
      conducted after the mission. Twelve patients were transported to Korea, and four
      critically ill patients were transported to the U.S. Army Burn Center in San
      Antonio, TX. The latter mission required 21 hours of in-flight critical care and
      was completed 4 days and 3 hours after the crash. After-action review resulted in
      changes in communications procedures, administrative oversight, supplies and
      equipment, composition of the Burn Flight Team, and readiness and training. These
      peacetime lessons contributed to the military's ability to transport wartime burn
      casualties in ensuing years and indicate the close interdependence of the
      disaster response and combat missions.

PMID- 16998397
TI  - Management of conventional mass casualty incidents: ten commandments for hospital
      planning.
AB  - The successful management of mass casualty incidents (MCIs) requires
      standardization of planning, training, and deployment of response. Recent events
      in the United States, most importantly the Hurricane season in 2005, demonstrated
      a lack of a unified response plan at local, regional, state, and federal levels.
      A standard Israeli protocol for hospital preparedness for conventional MCIs,
      produced by the Office of Emergency Preparedness of the Israeli Ministry of
      Health, has been reviewed, modified, adapted, and tested in both drills and
      actual events at a large university medical center in the United States. Lessons
      learned from this process are herein presented as the10 most important steps (ie,
      Commandments) to follow when preparing hospitals to be able to respond to
      conventional MCIs. The standard Israeli emergency protocols have proved to be
      universally adaptable, flexible, and designed to be adapted by any healthcare
      institution, regardless of its size and location.

PMID- 16998398
TI  - Practice guidelines for the management of pain.

PMID- 16998399
TI  - Cardiac molecular signaling after burn trauma.
AB  - Research using mammalian burn models has defined significant cardiac deficits
      after burn injury. The physiologic response to burn and burn complicated by
      sepsis, including the cardiac dysfunction associated with these insults, remains
      a very complex physiologic process which, despite active study, remains unclear.
      The well-characterized inflammatory mediators such as tumor necrosis factor
      alpha, interleukin-1beta, and interleukin-6 continue to play an active role in
      mediating cardiac dysfunction. However, perhaps of greater interest are the late
      mediators, high mobility group box 1 and macrophage migration inhibitory factor,
      because they offer a very realistic window for therapeutic intervention for
      controlling the inflammatory response. In addition, several other mediators of
      cardiac dysfunction have been identified and include the heat shock proteins,
      apoptosis, and the inflammatory caspases. These new mediators provide
      opportunities for therapeutic intervention, but further research is needed to
      clarify the importance of their mechanisms of action and the complex interactions
      between these various signaling pathways.

PMID- 16998400
TI  - Self-reports of anxiety in burn-injured hospitalized adults during routine wound
      care.
AB  - The purpose of this investigation was to examine the amount of anxiety patients
      believed tolerable and the amount of anxiety experienced during routine burn
      wound care. Participants included 47 hospitalized adults who provided data for
      four consecutive assessment periods. Patients (mean TBSA, 16%; range, 2-70%) were
      primarily Caucasian (87%) and had an average hospital stays of 23 days (range, 11
      130). Reports of what level of anxiety they would be able to tolerate and what
      level of anxiety had been experienced were assessed using 10-point Graphic Rating
      Scales. The use of anxiolytic was recorded, and patient suggestions for reducing
      anxiety were obtained. The single most commonly endorsed anxiety treatment goal
      was 0, although 53% consistently chose a treatment goal other than 0 (range, 1
      6). Two repeated-measure analyses of variance indicated that the amount of
      anxiety patients could tolerate and the amount they reported experiencing did not
      change over the course of time. Paired t-tests revealed that patients routinely
      reported more anxiety than they considered tolerable. Analyses of anxiety reports
      of patients treated with anxiolytics (n = 6) vs patients receiving no anxiolytics
      (n = 41) revealed inconsistent differences in actual anxiety and treatment goals
      across time. In general, patient suggestions for lessening anxiety included
      requests for education, communication, additional medications, and manipulation
      of the hospital environment. Anxiety for burn-injured, hospitalized adults
      remains a concern. Our findings are consistent with the literature indicating
      that adult patients hospitalized for burn wound care report appreciable anxiety,
      over and above what they consider "tolerable." Continued research is needed and
      should include investigations into the relationship between pain and anxiety
      during routine wound care.

PMID- 16998401
TI  - Effect of transforming growth factor-beta neutralization on survival and
      bacterial clearance in a murine model of Pseudomonas aeruginosa burn wound
      infection.
AB  - Transforming growth factor-beta (TGF-beta), a cytokine with anti-inflammatory
      properties, may contribute to postburn immunosuppression. This study was designed
      to determine whether neutralizing TGF-beta in burned mice could improve
      resistance to infection. C57BL/6J mice received a 35% TBSA flame burn under
      isoflurane anesthesia. Four days after injury, mice were treated with TGF-beta
      antibody or nonspecific IgG. On day 5 after burn injury, mice were inoculated
      with Pseudomonas aeruginosa at the burn wound site or received intraperitoneal
      injection with P. aeruginosa. Mice treated with anti-TGF-beta exhibited
      significantly improved survival compared with mice treated with nonspecific IgG
      after challenge with P. aeruginosa at the burn wound site or after
      intraperitoneal injection of P. aeruginosa. In mice with burn wound infections,
      bacterial counts in burn wounds, blood, and lung were decreased in mice treated
      with anti-TGF-beta compared with mice treated with control IgG. Bacterial counts
      in lung and blood after intraperitoneal challenge with P. aeruginosa also were
      significantly lower in burned mice treated with anti-TGF-beta compared with those
      treated with nonspecific IgG. Our data suggest that neutralization of TGF-beta at
      4 days after burn injury in mice improves local and systemic clearance of P.
      aeruginosa and enhances survival after P. aeruginosa challenge.

PMID- 16998402
TI  - Apoptotic cells are present in ischemic zones of deep partial-thickness burns.
AB  - Deep partial-thickness burns exhibit ambiguous behavior, either spontaneously
      healing or evolving into full-thickness burns. The aim of this study was to
      investigate these lesions for the presence of apoptotic cells and to compare
      their rate with that of superficial and full-thickness burns. We used
      colocalization of DNA fragments (ie, terminal deoxynucleotidyl transferase Biotin
      dUTP nick end labeling) and Fas ligand CD95 antibodies to calculate the apoptotic
      rate of superficial, deep partial-thickness and full-thickness burns in 45
      patients after the thermal injury. Biopsies were collected mainly during the
      acute postburn phase (first week of hospitalization). Deep partial-thickness
      burns presented apoptotic cells, both in the dermis and in cutaneous adnexa, and
      showed a higher apoptotic rate than superficial and full-thickness burns (44.5%
      in deep partial thickness, interquartile range 6.3-90.5%; 5.6% in superficial
      partial thickness, interquartile range: 0-13%; 0% for full-thickness burn; P =
      .000243). A significant greater apoptotic rate was present in cells of deep
      partial-thickness burns when compared with superficial and full thickness. These
      data would suggest that deep burns sustain an ischemic damage that forces cells
      to undergo apoptosis and could represent the biologic basis for their clinical
      evolution into full-thickness burns. Further correlation studies are now required
      to confirm this hypothesis.

PMID- 16998403
TI  - Effect of a fish oil and arginine-fortified diet in thermally injured patients.
AB  - Burn injury induces a hypercatabolic inflammatory state, predisposing burn
      patients to malnutrition, poor wound healing, and infectious complications. We
      conducted this study to determine what effect a diet fortified with fish oil and
      arginine (FAD) would have on wound healing in a thermally injured population.
      Twenty-three thermally injured patients were enrolled in this randomized double
      blind enteral feeding study from July 2002 to August 2004. All study patients
      received isonitrogenous enteral intragastric feeding within 48 hours of
      admission. Patients were randomized to our standard diet (STD, ProBalance with
      Promix, Probalance from Nestle, Glendale, CA; ProMix R.D., Navaco Laboratories,
      Phoenix, AZ) or a diet fortified with fish oil and arginine (FAD, Crucial, Nestle
      Nutrition Glendale, CA) Diets were advanced as tolerated to meet 100% of
      estimated needs. The primary endpoint of the study was time to heal the first
      donor site. There were no statistical differences between the study groups with
      respect to baseline characteristics. Both diets were well tolerated, and there
      were no differences in the daily total kilocalories or protein intake per
      kilogram between the two diet groups throughout the study. Although
      nonsignificant, the patients in the FAD group showed a slightly faster healing
      time than those in the STD group (10.8 +/- 2.7 days vs 12.3 +/- 5.2 days,
      respectively). This trend was further accelerated when those with body surface
      area burns less than 30% were examined (patients with body surface area burns
      <30% in the FAD healed in 9.0 +/- 1.7 vs corresponding patients in the standard
      group who healed in 12.2 +/- 6.2, P = .63). Patients in the FAD group trended to
      more infections and more adverse complications. The adverse complications were
      predominantly associated with inhalation injuries. The role of fortified enteral
      diets in the outcomes of thermally injured patients deserves further study. Such
      a future study should be conducted in a multicenter trial and involve inhalation
      injury stratification systems to accurately score and randomize patients for
      inhalation injury. Finally, the frequency and pattern of infections in patients
      receiving fortified enteral diets deserves further evaluation.

PMID- 16998404
TI  - Profile of patients lost to follow-up in the Burn Injury Rehabilitation Model
      Systems' longitudinal database.
AB  - We sought to identify whether patterns exist in the Burn Injury Rehabilitation
      Model Systems' database among participants lost to follow-up at 6, 12, or 24
      months after injury and to define characteristics that reliably discriminate
      between persons who are lost to follow-up and those who are not. All participants
      met the American Burn Association criteria for major burn injury, were 18 years
      of age or older, received care from one of four burn model systems, and consented
      to participate in a 2-year prospective data-collection process. Step-wise
      logistic regression was used to develop three prediction models for the
      probability of loss to follow-up. The percent of individuals successfully
      contacted for follow-up were 64% at 6 months, 54% at 12 months, and 42% at 24
      months after injury. Individuals who were younger, not employed at time of burn,
      with less than a high school level education, a history of drug abuse,
      circumstances of injury involving suspected assault, and having no insurance for
      care were lost to follow-up. Longer stay in the hospital, on the other hand,
      increased the likelihood of follow-up. The same risk factors remained significant
      with or without adjusting for site indicating that these factors are independent
      and significant in spite of any potential site differences. Successful follow-up
      at 6- and 12-month intervals increased the likelihood of achieving a follow-up at
      24 months after injury. The sociodemographic risk factors for attrition
      identified in this study represent significant enduring vulnerabilities. The
      findings necessitate a close examination of several factors and the use of
      strategies to reduce the risk of attrition.

PMID- 16998405
TI  - Mechanical and infectious complications of central venous cannulation in
      children: lessons learned from a 10-year experience placing more than 1000
      catheters.
AB  - We sought to better describe the expected incidence of mechanical and infectious
      complications associated with central venous cannulation of critically ill
      children. We undertook a retrospective analysis of a prospective data collection
      of 1056 consecutive percutaneous central venous catheters inserted under the
      supervision of an experienced surgeon. There were 245 (23%) subclavian (SC), 118
      (11%) internal jugular (IJ), and 693 (66%) femoral (F) catheters placed in 289
      children with an average age of 6.4 +/- 5.1 years (range, 4 weeks to 18 years)
      admitted to a burn intensive care unit. Catheter sepsis occurred in 7.4% of SC,
      7.6% of IJ, and 4.9% of F catheters (NS, P = .25), for an overall sepsis rate of
      5.8%. The number of catheter lumens did not impact infection rate. Infection
      rates increased in catheters left in situ more than 10 days, increasing to 37.5%
      at 14 days. Acute mechanical complications occurred in three insertions (0.3%),
      including two (0.8%) SC, zero (0%) IJ, and one (0.1%) F catheters (NS, P = .20).
      All three were arterial cannulations that were recognized and treated
      successfully without surgery. There were no pneumothoraces, vascular lacerations,
      acute thromboses, or catheter emboli. There were six (0.6%) cases of deep venous
      thrombosis that occurred in cannulated sites: one (0.4%) SC, two (1.6.%) IJ, and
      three (0.4%) F sites (NS, P = .23). Patient age did not influence complication
      rates. A total of 239 (23%) of the CVCs were placed in infants less than 24
      months; 273 (26%) 2 to 5 years, 259 (25%) 6 to 10 years, and 285 (27%) >10 to 18
      years. Catheter sepsis occurred in 6.7%, 5.9%, 6.2%, and 4.6%, respectively (NS,
      P = .75). There was no difference in rates of infection or mechanical
      complication between younger and older children. When closely supervised by an
      experienced surgeon, a low rate of infection (5.8%), acute mechanical
      complication (0.3%), and deep venous thrombosis (0.6%) accompanies central venous
      cannulation of critically ill children.

PMID- 16998406
TI  - Pain during burn hospitalization predicts long-term outcome.
AB  - Acute pain after medical procedures is often undertreated, opioid analgesics are
      used far too sparingly, and patients are forced to suffer needlessly as a result.
      Attempts to change health care practitioner behavior in the area of pain control
      are often futile. The purpose of the current study was to provide empirical
      evidence that supports the deleterious impact of acute pain. A prospective,
      longitudinal study was designed to assess the impact of pain during burn
      hospitalization on postdischarge follow-up of 122 patients. A composite score of
      patient ratings of procedural pain during hospitalization was composed.
      Regression analyses were used to compare the extent to which pain predicted long
      term adjustment relative to potential competing variables such as the length of
      hospitalization, preinjury adjustment, and coping style. Pain during
      hospitalization was significantly associated with psychological adjustment at 1
      month (53% return), 1-year (46% return) and 2-year (33% return) follow-up.
      Regression analyses indicate that pain was a stronger predictor than the size of
      the burn or length of hospitalization, and that this correlation could not be
      attributed to the patients' preinjury mental health history or coping style (for
      the 1-month and 1-year follow-up periods). Pain during hospitalization had a
      significant and enduring relationship with adjustment after burn injuries.
      Although causality cannot be definitively determined, the study findings provided
      compelling evidence for the value of controlling acute pain during
      hospitalization.

PMID- 16998407
TI  - The presence of nightmares as a screening tool for symptoms of posttraumatic
      stress disorder in burn survivors.
AB  - Recurrent nightmares can be a symptom of posttraumatic stress disorder (PTSD).
      This study evaluated the method of asking burn survivors about nightmares as a
      screening tool for the presence of PTSD symptomatology. The presence of
      nightmares in 85 individuals treated at the Burn Center in Uppsala, Sweden,
      between 1996 and 2000 (23 women, 62 men, average age 47 years, average burn size
      17% TBSA, average time after burn 3.6 years) was evaluated by one question from
      the Burn Specific Health Scale (BSHS) and by using the Diagnostic and Statistical
      Manual of Mental Disorders, 4th edition criteria for nightmares. PTSD
      symptomatology was assessed with the Impact of Event Scale-Revised. Sensitivity,
      Specificity, Discriminant Ability, and Likelihood Ratios for a positive and a
      negative result were calculated to evaluate the screening questions. As many as
      46% of the burn survivors reported nightmares of some frequency in the BSHS and
      as many as 28% when using the Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition criteria. Both approaches were useful tools for detecting
      or ruling out PTSD symptoms. The best Discriminant Ability was achieved with a
      screening test using the BSHS item "I have nightmares." Screening questions for
      presence of nightmares after burns can be useful in detecting PTSD
      symptomatology.

PMID- 16998408
TI  - Emotional distress and psychosocial resources in patients recovering from severe
      burn injury.
AB  - Emotional distress as well as psychosocial resources in 55 patients with burn
      injuries was assessed during acute and follow-up treatment. Results showed
      significantly greater values of emotional distress among patients when compared
      with norms of the general population. As well as higher levels of general
      psychopathology, particularly prevalent were anxiety, depression, and
      posttraumatic symptoms. However, patients also reported high levels of resources
      such as general optimism, self-efficacy, and perceived social support. Within the
      sample, no significant correlation between severity of emotional distress and
      severity of burn injury was found. By psychological assessments a subgroup of
      highly distressed patients was identified. These patients were highly emotionally
      distressed while having objective injury severity comparable with the other
      patients in the sample. Reactions to burn accidents vary individually. The
      results demonstrate the importance of routine screenings of psychological
      symptoms. An early identification of patients at-risk allows for tailored
      psychotherapeutic interventions and can thus help to improve quality of life and
      general well-being of burn patients on a long-term basis.

PMID- 16998409
TI  - Hypothalamic-pituitary-adrenal axis response to sustained stress after major burn
      injury in children.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is responsible for stress response
      after injury, yet its function after severe burn injury in children is unclear.
      The purpose of this study was to define the effects of burn injury on the HPA
      axis and to evaluate the utility of total serum cortisol in measuring adrenal
      function in children with major burns in the 2 months after injury. Children ages
      0 to 17 years who were admitted within 72 hours to our pediatric burn center with
      20% TBSA or greater full-thickness burns were eligible for the study. Serum total
      cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone,
      vasopressin, Pediatric Risk of Mortality (PRISM) score, serum albumin level, and
      electrolytes were obtained on admission and weekly for 8 weeks. An ACTH
      stimulation test (250 microg for children >2 years, 125 microg for children < or
      =2 years) was administered weekly at 8:00 am. Total serum cortisol was measured
      before and 60 minutes after the administration of ACTH. Twenty-five children with
      mean age 7.6 +/- 1.1 years and TBSA burn 41.8 +/- 3.8% were enrolled in the
      study. Baseline total serum cortisol was 12.4 +/- 0.7 microg/dl in the 8 weeks
      after injury and increased to 24.4 +/- 0.8 microg/dl after the administration of
      ACTH. Cortisol level did not correlate with PRISM score, albumin, vasopressin,
      ACTH, or mortality. Although the adrenal response to acute and chronic stress is
      intact after severe burn injury, the ACTH/adrenal feedback loop is disrupted.
      Random total serum cortisol measurements overestimate adrenal dysfunction; thus,
      ACTH stimulation testing should be used to assess adrenal function before the
      administration of exogenous steroids.

PMID- 16998410
TI  - Septic hip presenting with dislocation as a source of occult infection in a burn
      patient.
AB  - An 11-year-old boy was transferred to a regional burn center after sustaining 53%
      TBSA burns. Initial wound cultures grew multiple organisms. Multiresistant
      Klebsiella was cultured from the patient's blood. When the patient indicated
      worsening hip pain, radiographs revealed a spontaneous hip dislocation. Immediate
      arthrotomy revealed left hip synovial fluid infected with Klebsiella. The patient
      remained afebrile and was discharged home 6 months after admission.

PMID- 16998411
TI  - Successful treatment of burn and visceral injury combined with full-thickness
      loss of the abdominal wall after blast injury.
AB  - A 29-year-old man was admitted to our institution 10 days after he had undergone
      an urgent exploratory laparotomy at a local army hospital after a terrorist
      bombing attack. On admission, deep second-degree and third-degree burns involving
      25% of the upper and lower extremities were present, together with a 25 x 10-cm
      abdominal full-thickness blast injury defect on the left side, an infected
      eviscerated midline incision, and a colostomy on the right side of the abdomen.
      The patient underwent a second laparotomy, at which time the intraabdominal
      abscess was drained, and the abdominal cavity was irrigated with saline. A
      jejunal perforation was found and sutured. The abdominal cavity was left open and
      covered with a Bogota bag for temporary closure. On postburn day 18, the patient
      underwent debridment and grafting of the third-degree burns to the left and right
      arm and right lower extremities. After several debridment sessions (postburn days
      16, 18, 20, 22, and 24), an abdominal skin release and reapproximation were
      performed (postburn day 26). On postburn day 36, split-thickness skin grafts were
      placed directly on the granulated tissue of the intestines and on a defect in the
      left flank and iliac regions. Postoperatively, the patient did well. He was
      discharged on postburn day 78 with all wounds well healed. In our opinion,
      temporary closure followed by direct application of meshed split-thickness skin
      grafts to exposed abdominal viscera represents a simple method of reconstruction
      that can be safely performed, with minimal risk, on critically ill patients.

PMID- 16998412
TI  - Gastric rupture after cardiopulmonary resuscitation in a burn patient.
AB  - Burn injury, especially severe facial burn injury, poses a unique challenge for
      emergency health care personnel in administering cardiopulmonary resuscitation.
      Because of the perioral and oral edema with severe facial burns, intubation may
      be difficult, and bag-valve mask or mouth-to-mouth resuscitation may be
      prolonged. As a result of the difficulty in establishing a patent airway, various
      complications can arise. One of these includes gastric perforation which,
      although rare in the setting of difficult intubation or prolonged oral
      ventilation, may be possible. To our knowledge, acute gastric perforation after
      prolonged cardiopulmonary resuscitation in burn injured patients has not
      previously been reported thus the incidence is unknown. We report here a case of
      gastric perforation after a difficult tracheal intubation in a patient with
      extensive burns of the head and neck and 63% TBSA burn.

PMID- 16998413
TI  - Ketamine may be the first choice for anesthesia in burn patients.

PMID- 16998415
TI  - Predictors of relapse in bipolar disorder: A review.
AB  - INTRODUCTION: Bipolar disorder is the sixth leading cause of disability in the
      United States. Moreover, repeated episodes and non-responsiveness to treatment
      continue to present a significant problem, and little is known about the factors
      that may precipitate relapse. This article reviews the available literature on
      predictors of bipolar relapse. METHODS: We conducted a literature search on
      Medline from 1996 to March 2006, using the keywords "relapse," "recurrence,"
      "compliance," "adherence," "life events," "kindling," and "predictors" combined
      with the term "bipolar disorder(s)." References from the resulting articles also
      supplemented the initial search. Thirty-eight articles were included in the
      analysis. RESULTS: Predictors of episodes include stressful life events,
      increased number of previous episodes, decreased interval between episodes, and
      persistence of affective symptoms and episodes. Factors associated with longer
      survival times include psychotherapy, social support, and medication adherence.
      CONCLUSIONS: Our review suggests several reliable predictors of bipolar episodes.
      Knowledge of these factors has significant clinical implications and could aid in
      treatment and prevention strategies. However, further research is clearly needed
      to address the limitations of the existing research and to increase our
      understanding of predictors of relapse, with the intent of improving quality of
      life and preventing episodes in patients with bipolar disorder.

PMID- 16998416
TI  - Maintenance treatment of bipolar disorder: Applying research to clinical
      practice.
AB  - The authors review available controlled trials of bipolar maintenance treatment
      and discuss the strengths and weaknesses of various study designs. Bipolar
      maintenance trials are organized according to the features of their designs, such
      as use of responder-enriched samples; inclusion following an index manic versus
      an index depressive episode; outcome defined as relapse into mania, depression,
      or either; and use of survival analysis. Pivotal studies of lithium, divalproex,
      lamotrigine, olanzapine, aripiprazole, and other medications are reviewed. The
      directional efficacy of the different medications as maintenance treatment is
      discussed, with treatments differentiated in terms of whether they primarily
      prolong time to mania or to depression or have bidirectional effects. Also
      discussed are findings concerning the continuation of acute treatments, including
      antidepressants, into the maintenance phase; dosage adjustments for maintenance
      treatment; the rationale for combination treatments; and implications of comorbid
      substance abuse and strategies for its management. Directions for future research
      are suggested.

PMID- 16998417
TI  - Long-term lamotrigine plus lithium for bipolar disorder: One year outcome.
AB  - OBJECTIVE: To obtain pilot data in an observational setting on the use of
      lamotrigine plus lithium in the long-term treatment of patients with bipolar
      disorder, 87% of whom had failed to respond to at least one previous mood
      stabilizer. METHODS: Charts of 21 patients (11 females, 10 males, mean age 43.2
      years) treated with the combination of lithium and lamotrigine were reviewed
      retrospectively for treatment response using the Clinical Global Impression
      Bipolar Disorder-Improvement scale, divided into benefit for acute depressive
      symptoms, acute manic symptoms, and overall illness (including prophylaxis of
      mood episodes). Of the 21 patients, 76% were diagnosed with bipolar I disorder,
      and depressive symptoms were the most common acute indication for treatment
      (52%). Mean doses of lithium and lamotrigine were 963 mg/day and 179 mg/day,
      respectively, used for a mean of 55.7 weeks. RESULTS: Acute antidepressant
      benefit was observed in 48% of patients, acute anti-manic benefit in 14%, and
      overall prophylactic benefit in 29%. Side effects were observed in 38%, with
      cognitive problems most common (29%). 48% discontinued combination therapy,
      mainly due to lack of efficacy (19%) or activation of manic-like symptoms (19%).
      CONCLUSIONS: Among a group of largely treatment-resistant bipolar patients, the
      combination of lithium and lamotrigine appeared effective for acute depressive
      symptoms in about half of the patients, but acute anti-manic and long-term
      prophylactic efficacy appeared less robust.

PMID- 16998418
TI  - Risperidone in cocaine-dependent patients with comorbid psychiatric disorders.
AB  - BACKGROUND: : A high percentage of individuals with cocaine dependence have a
      comorbid psychiatric illness, which complicates treatment of the substance abuse.
      This report will describe clinical experience using risperidone in cocaine
      dependent patients with psychiatric disorders. METHOD: : Sixteen male patients
      with cocaine dependence and comorbid psychiatric disorder (DSM-III-R) diagnoses,
      who were admitted to a voluntary, post-detoxification, intermediate-care
      inpatient substance abuse program, were started on risperidone (mean starting
      dose 2.3 mg/day) in an open-label, naturalistic trial. Patients were assessed
      weekly using the Clinical Global Impressions scale to assess overall functioning,
      a Likert scale for craving, the Abnormal Involuntary Movement Scale, interviews
      with substance abuse counselors and patients, and laboratory tests. All patients
      had at least one other substance use diagnosis besides cocaine dependence, and 13
      patients were taking another psychiatric medication. RESULTS: : Of the 16
      patients, 13 (81%) were rated improved or much improved on the CGI scale, and all
      patients reported mild or no craving at the last assessment (after a mean of 32.6
      days of risperidone treatment). No patient developed extrapyramidal symptoms or
      hypomania. Compared to a 32% historical completion rate for patients receiving
      treatment as usual, fourteen (88%) of these patients completed the program, and 9
      moved on to the next level of care. CONCLUSION: : The results of this
      naturalistic trial suggest that risperidone is safe and well tolerated in
      patients with cocaine dependence and comorbid psychiatric illness. In the short
      term, risperidone may also be effective in reducing cocaine craving and use and
      may increase the likelihood of completing substance abuse treatment.

PMID- 16998419
TI  - Clinically relevant pharmacology of neuropsychiatric drugs approved over the last
      three years: Part II.

PMID- 16998420
TI  - A psychodynamic perspective on relational structures.

PMID- 16998421
TI  - Treating antisocial syndromes.

PMID- 16998422
TI  - Using the internet for clinical information gathering about unidentified
      psychiatric patients.

PMID- 16998423
TI  - Adjuvant galantamine for cognitive dysfunction in a patient with bipolar
      disorder.

PMID- 16998424
TI  - Remission of positive and negative symptoms in refractory schizophrenia with a
      combination of haloperidol and quetiapine: Two case studies.

PMID- 16998425
TI  - Ultrasonographic examination for inversion ankle sprains associated with osseous
      injuries.
AB  - OBJECTIVE: The study attempted to evaluate the value of ultrasonography in
      determining the therapeutic strategy for patients with osseous injuries caused by
      ankle sprains. DESIGN: A 10-MHz compact linear-array ultrasound transducer was
      used to assess patients with inversion ankle sprains. Eleven female and 12 male
      patients who had fractures detected by sonograms were included in the study. All
      23 patients underwent radiographic examination for identification of fractures.
      Bone scintigraphy was performed for those who had negative x-ray findings.
      RESULTS: Eighteen patients had distal fibular tip fractures, three patients had
      the fifth metatarsal base fractures, one patient had a talar neck fracture, and
      one patient had a navicular fracture. These fractures were all detected by
      ultrasonography and then proved even by radiography or by bone scans. All the 23
      patients had anterior talofibular ligament injuries. Among these patients, 11 had
      anterior ankle-joint recess effusion, and two had additional anterioinferior
      tibiofibular ligament injuries. Six weeks of immobilization with the ankle
      fracture brace was prescribed for all the patients after the identification of
      fractures. Their ankle pain symptoms soon improved. CONCLUSIONS: Ultrasonography
      is valuable in evaluating tiny foot and ankle fractures and coexistent soft
      tissue injuries. It can guide the treatment for patients with osseous injuries
      caused by ankle sprains.

PMID- 16998426
TI  - Day-of-injury computerized tomography, rehabilitation status, and development of
      cerebral atrophy in persons with traumatic brain injury.
AB  - OBJECTIVE: To compare day-of-injury (DOI) computerized tomography (CT) findings
      with acute injury severity markers, disability at acute hospital admission and
      discharge from inpatient rehabilitation, injury severity markers, and degree of
      postacute cerebral atrophy on magnetic resonance imaging (MRI). DESIGN:
      Retrospective chart review of 240 consecutive traumatic brain injury (TBI)
      admissions (mean age 31.7 +/- 15.8 yrs) with moderate-to-severe initial brain
      injury. All DOI CT abnormalities were qualitatively rated. Disability was
      assessed using the Disability Rating Scale (DRS) and the FIM measure. In a
      representative subset, cerebral atrophy was determined by the ventricle-to-brain
      ratio (VBR) method and quantified from MRI scans 25 or more days postinjury.
      RESULTS: CT classification resulted in nonsignificant differences in DRS and FIM
      ratings at the time of discharge from the rehabilitation unit, except in
      brainstem injury subjects who had significantly higher DRS and lower FIM scores
      at rehabilitation discharge. At 25 or more days postinjury, presence of any DOI
      CT abnormality was associated with larger VBR. Increased VBR, as an index of
      cerebral atrophy, was associated with worse rehabilitation discharge DRS and FIM
      ratings. CONCLUSIONS: Other than brainstem injury, DOI CT findings relate poorly
      to rehabilitation outcome. Presence of DOI CT abnormalities were associated with
      the development of cerebral atrophy, which was associated with poorer
      rehabilitation discharge DRS and FIM scores.

PMID- 16998427
TI  - Concordance in goal setting between patients with multiple sclerosis and their
      rehabilitation team.
AB  - OBJECTIVE: To determine the concordance between patients with multiple sclerosis
      and their clinical team members on the identification of goals for an inpatient
      rehabilitation stay. DESIGN: Prospective cohort study of patients admitted for
      rehabilitation in an adult inpatient neurospinal unit at a Rehabilitation Centre
      in Ottawa, Canada. Twenty-seven patients (11 men and 16 women, mean age of 45.3
      yrs) with either a laboratory or a clinically supported diagnosis of multiple
      sclerosis. Patients rated 55 goals from a preexisting list, indicating the
      importance of each goal to be addressed during the inpatient stay. The goals fell
      into five broad domains of health/medical issues, daily activities, mobility,
      community life, and personal well-being. Patients also identified their five most
      important individual goals. In a separate session, the clinical team also rated
      the 55 goals in relation to each patient and identified an independent list of
      the five most important rehabilitation goals. Main outcome measures included
      concordance between patient and team ratings in the identification of goals,
      ratings of the likelihood of success of achieving each goal, and ratings of the
      amount of change required to realize a minimal clinically important difference.
      RESULTS: The patients and the team agreed on an average of 1.7 of the patient's
      five top-rated goals. Compared with the team, patients gave higher importance
      ratings to goals within the health/medical, mobility, and daily activities
      domains. They also considered that a greater average improvement would be
      required to achieve a meaningful benefit, and they gave higher ratings of the
      likelihood of success in achieving their selected goals. CONCLUSION: Patients
      with multiple sclerosis and clinical team members do not necessarily agree on
      specific goals for a rehabilitation stay. Patients may also have greater
      expectations than clinicians with respect to the amount of improvement and the
      likelihood of achieving their goals.

PMID- 16998428
TI  - Do racial disparities exist in access to inpatient stroke rehabilitation in the
      state of Maryland?
AB  - OBJECTIVE: Black patients tend to have a greater number and severity of stroke
      cases. The literature on access to rehabilitative services shows mixed results
      ranging from no disparities to limited access among minority populations. This
      study evaluated the association of race and acute discharge to inpatient stroke
      rehabilitation in Maryland, a diagnostic related group-and postacute care
      prospective payment system-exempt state. DESIGN: Data from the Maryland Health
      Services and Cost Review Commission database for 2000 was used to conduct a cross
      sectional retrospective review to determine the rate of disposition to inpatient
      rehabilitation facilities (IRF). Multiple logistic regression analyses evaluated
      factors associated with discharge to IRF in this population. RESULTS: There were
      a total of 12,208 patients hospitalized with stroke in the year 2000. Compared
      with urban-dwelling white patients, black patients who lived in urban dwellings
      were more likely to be discharged to IRF, OR 1.42, 95% CI (1.06, 1.91).
      CONCLUSION: In the state of Maryland, urban-dwelling black stroke patients were
      more likely to be discharged to IRF acutely after stroke. Future studies should
      assess whether this trend persists in states that have larger rural populations.

PMID- 16998429
TI  - Task-oriented intervention in chronic stroke: changes in clinical and laboratory
      measures of balance and mobility.
AB  - OBJECTIVE: The objective of this study was to evaluate whether, after a task
      oriented exercise program, the changes in clinical measures of balance and
      mobility were paralleled by changes in biomechanical parameters in subjects with
      chronic stroke. DESIGN: Ten stroke subjects took part in an 8-wk exercise program
      aimed at improving balance and mobility through various functional tasks.
      Subjects were evaluated before and after the exercise intervention. Clinical
      measures included the Berg Balance Scale and the Timed-Up-and-Go and laboratory
      measures included ground reaction forces and center of pressure displacement
      during four functional tasks. RESULTS: Stroke subjects showed significant
      improvements (P < 0.05) in the clinical measures after completing the exercise
      program. Significant improvements (P < 0.05) were also found in postural
      steadiness during tandem stance and stool touch and in force production through
      the paretic lower limb during sit-to-stand. This last result was strongly
      correlated (r = -0.93) with the improvements on the Timed-Up-and-Go after
      exercise intervention. In contrast, the increase in postural steadiness was
      poorly correlated with the improvements on the Berg Balance Scale. CONCLUSIONS: A
      task-oriented exercise program might improve both clinical and laboratory
      measures of balance and mobility in stroke subjects. However, several
      correlations between the changes in clinical and laboratory measures after
      exercise intervention were generally weak, indicating that these outcome measures
      assessed different components of improvements.

PMID- 16998430
TI  - Functional status and health-related quality of life during inpatient stroke
      rehabilitation.
AB  - OBJECTIVE: To examine changes in functional status and health-related quality of
      life (HRQOL) during inpatient stroke rehabilitation to examine the associations
      between changes in the two measures. DESIGN: Two independently collected
      databases were combined for a retrospective analysis. One contained the
      objectively assessed FIM score; the other contained the subjectively assessed
      Medical Outcomes Study 36-item short form (SF-36). Admission and discharge scores
      were compared using paired-samples t tests. Associations between the FIM outcomes
      and the SF-36 outcomes were assessed by means of Pearson's product-moment
      correlations. RESULTS: One hundred sixteen patients were represented in both
      databases. Mean age was 71.4 yrs; 59 (51.1%) were female. All FIM scores, four of
      eight SF-36 domains, and one summary component score showed statistically
      significant improvement during the course of rehabilitation. Changes in SF-36
      were not strongly associated with changes in FIM score, with only 6 of 90
      correlations attaining statistical significance. CONCLUSIONS: Functional status
      and HRQOL improved considerably over the course of rehabilitation. However, there
      was poor association between the two outcomes. Both instruments offer insights
      into outcomes of inpatient rehabilitation, but they are complementary rather than
      overlapping.

PMID- 16998432
TI  - The use of complementary and alternative medicine in children with chronic
      medical conditions.
AB  - OBJECTIVES: The objectives of this study were to examine whether progressive
      medical conditions lead to greater use of complementary and alternative medicine
      (CAM) as compared with more stable conditions, to see whether disease severity
      influences CAM use, and to identify the main motivations behind CAM use. METHODS:
      Subjects were selected from outpatient clinics at Hotel Dieu Hospital. Surveys
      were conducted by mail and telephone. Medical diagnosis and severity were
      obtained from medical files. Statistical tests included chi, Kruskal-Wallis, and
      correlations. RESULTS: One hundred ninety-four children were surveyed. The
      "progressive" group included 15 patients with Duchenne muscular dystrophy and 22
      patients with cystic fibrosis. The "nonprogressive" group included 85 patients
      with cerebral palsy (CP), 49 with diabetes mellitus, and 23 with spina bifida.
      Twenty-three percent were using CAM. CP had the highest use; diabetes mellitus
      had the lowest. Popular therapies included massage and dietary/herbal remedies.
      Progressiveness had no impact on CAM use. Within the CP group, greater disease
      severity was associated with higher use (P < 0.001). The main reason for CAM use
      was to complement conventional medicine. CONCLUSIONS: Disease progressiveness had
      no impact on CAM use, but severity within the CP group did. Complementing
      conventional medicine was the main motive. Understanding the reasons and patterns
      of use of CAM is beneficial in efforts to improve the care of children with
      chronic medical conditions.

PMID- 16998433
TI  - Effectiveness of physical training on motor performance and fall prevention in
      cognitively impaired older persons: a systematic review.
AB  - OBJECTIVE: To determine whether older cognitively impaired people benefit from
      physical training with regard to motor performance or fall risk reduction and to
      critically evaluate the methodologic approach in identified randomized controlled
      intervention trials. DESIGN: Published randomized controlled intervention trials
      from 1966 through 2004 were identified in PubMed, CINAHL, Gerolit, and the
      Cochrane Central Register of Controlled Trials according to predefined inclusion
      criteria and evaluated by two independent reviewers using a modified rating
      system for randomized controlled intervention trials developed by the Cochrane
      Library. RESULTS: There were 11 randomized controlled intervention trials that
      met the predefined inclusion criteria. There was a large heterogeneity regarding
      methodology, sample size, type of intervention, study outcomes, and analyses. We
      found conflicting evidence regarding the effect of physical training on motor
      performance and falls in older people with cognitive impairment. However, a
      considerable number of the studies had methodologic limitations, which hampered
      the evaluation of the effectiveness of training. CONCLUSIONS: The randomized
      controlled intervention trials showed only limited effectiveness of physical
      training in patients with cognitive impairment. More studies with adequate sample
      size, sensitive and validated measurements, and higher specificity for the types
      of intervention targeting subgroups of patients with different degrees of
      cognitive impairment are required to give evidence-based recommendations.

PMID- 16998435
TI  - Lumbosacral magnetic root stimulation in lumbar plexopathy.
AB  - We report a 76-yr-old man with left femoral nerve distribution weakness resulting
      from a nontraumatic retroperitoneal hematoma associated with coumadin
      anticoagulation. Although electric root stimulation was relatively
      contraindicated, magnetic lumbosacral root stimulation identified a proximal
      conduction block allowing more extensive assessment of the nerve damage. To our
      knowledge, this is the first report of magnetic root stimulation in assessment of
      lumbosacral plexus dysfunction in retroperitoneal hematoma.

PMID- 16998436
TI  - Neuropathic arthropathy.

PMID- 16998437
TI  - Comparison of the VO2 response to 800-m, 1500-m and 3000-m track running events.
AB  - AIM: The present study examined the VO2 response to middle-distance track running
      events of 800 m, 1500 m and 3000 m and investigated the relationship between the
      speed of the VO2 response ((1) and subsequent race performance. METHODS: Trained
      3000-m (n = 8), 1500-m (n = 10) and 800-m (n = 8) male track athletes performed a
      laboratory GXT plus a run at 14 km x h(-1) and multiple race time trials. For
      each subject, a bi-exponential model fit from 20 s was used to categorise the O2
      response for the best performed track run and also the treadmill run at 14 km x
      h(-1). RESULTS: Faster (1 values were noted the shorter the track event, with
      values of 14, 18.5 and 20.8 s for 800-, 1500- and 3000-m events, respectively.
      ANOVA results revealed that differences in (1 were significant (P < 0.05) for the
      800- and 3000-m, but not for the 800- and 1500-m (P = 0.06) or 1500- and 3000-m
      events (P = 0.15). Only 1500-m race performance was significantly correlated to
      race (1 (r = 0.71). Values for (1 at an absolute velocity treadmill run (14 km x
      h(-1)) did not differ significantly between different events and were not
      correlated to race performance for any event. From pooled data for all three
      events, significant correlations (P < 0.01) were noted between tau1 and the speed
      over the first 800-m (r = -0.54 to -0.68). CONCLUSIONS: There was a trend for
      faster (1values the shorter the track event. The significant correlation between
      tau1 and initial starting velocity suggests this may be attributed to the faster
      starting velocity of the shorter track events, rather than any differences
      between athletes per se.

PMID- 16998438
TI  - Physiological differences of elite and professional road cyclists related to
      competition level and rider specialization.
AB  - AIM: The aim of this investigation was to study the physiological response to
      laboratory tests in elite and professional cyclists, and to relate it to the
      level at which riders compete and their specialization. METHODS: A total of 71
      cyclists were divided into two groups, elite and professional, and were assessed
      for physical measurements, a maximal graded test and a 30 s all-out test, both
      performed on a cycle ergometer. The sample included 24 uphill riders (UR), 32
      flat terrain riders (FTR), 11 all terrain riders (ATR) and 4 sprinters (SP).
      RESULTS: Professional riders showed significantly higher gross mechanical
      efficiency (GME) than their elite counterparts (25.6+/-2.6 vs 24.4+/-2%), but
      otherwise no other physiological differences emerged from the comparison between
      these two groups. However, many differences exist as a function of rider
      specialization, especially between UR and FTR. Compared with FTR, UR showed a
      higher VO2max (78.2+/-5.5 vs 72.6+/-6.5 mL x min(-1) x kg(-1)) and a lower
      maximal aerobic power (438.5+/-40.8 vs 465.3+/-36.2 W). From the 30 s all-out
      test, SP presents the highest maximal power (P < 0.05) and maximal velocity (P <
      0.05) compared with all the other groups. CONCLUSIONS: The results for GME
      indicate a better efficiency for professional riders and suggest the importance
      of technical aspects related to movement pattern in cycling. The sensitivity of
      the maximal graded test and the 30 s all-out test did not allowed other
      differentiations between elite and professional cyclists.

PMID- 16998439
TI  - Measuring and predicting maximal aerobic power in international-level
      intermittent sport athletes.
AB  - AIM: The purpose of this study was to measure actual VO2max during the multi
      stage fitness test (MSFT) and to compare this with predicted values obtained
      using previously established, commonly used methods. We also wanted to determine
      a new and more accurate regression equation for the prediction of VO2max in
      intermittent sport athletes. METHODS: Twenty-six, elite, male, intermittent sport
      athletes performed the MSFT with oxygen uptake (VO2) and heart rate (HR) measured
      throughout. Paired t-tests were used to compare measured VO2max with predicted
      VO2max. Linear regression was used to determine the equation for the prediction
      of VO2max from the total number of shuttles completed. RESULTS: There were no
      differences between the two methods of predicting VO2max, however, both predicted
      values (53.6+/-3.9 and 51.3+/-4 mL x kg(-1) x min(-1)) were significantly lower
      (9.3% and 13.2%, respectively) than measured VO2max (59.1+/-6.6 mL x kg(-1) x
      min(-1), P < 0.001). Correlations between measured and predicted VO2max were
      similar for both prediction methods (r = 0.61, P = 0.013 and r = 0.68 and P =
      0.004). We present a new prediction equation [Y (VO2max, mL x kg(-1) x min(-1)) =
      0.38 x total number of shuttles completed +25.98] (where R = 0.69; R2 = 0.48; SEE
      = 4.9 mL x kg(-1) x min(-1); SEE% = 8.3) which provides a more valid method of
      predicting actual max in intermittent sport athletes. CONCLUSIONS: A new
      regression equation to predict VO2max in intermittent sport athletes has been
      established. Whilst some error in predicting VO2max still exists, the new
      equation will provide coaches and sport-scientists with a more suitable equation
      with which to predict VO2max in intermittent sport athletes.

PMID- 16998440
TI  - Does net energy cost of swimming affect time to exhaustion at the individual's
      maximal oxygen consumption velocity?
AB  - AIM: The purpose of the present study was to examine the relationship between
      time limit at the minimum velocity that elicits the individual's maximal oxygen
      consumption (TLim-v VO2max) and three swimming economy related parameters: the
      net energy cost corresponding to v VO2max (Cv VO2max), the slope of the
      regression line obtained from the energy expenditure (E) and corresponding
      velocities during an incremental test (C(slope)) and the ratio between the mean E
      value and the velocity mean value of the incremental test (C(inc)).
      Complementarily, we analysed the influence of Cv VO2max, C(slope) and C(inc) on
      TLim-v VO2max by swimming level. METHODS: Thirty swimmers divided into 10 low
      level (LLS) (4 male and 6 female) and 20 highly trained swimmers (HTS) (10 of
      each gender) performed an incremental test for v VO2max assessment and an all-out
      TLim-v VO2max test. RESULTS: TLim-v VO2max, v VO2max, Cv fVO2max, C(slope) and
      C(inc) averaged, respectively, 313.8+/-63 s, 1.16+/-0.1 m x s(-1), 13.2+/-1.9 J x
      kg(-1) x m(-1), 28+/-3.2 J x kg(-1) x m(-1) and 10.9+/-1.8 J x kg(-1) x m(-1) in
      the LLS and 237.3+/-54.6 s, 1.4+/-0.1 m x s(-1), 15.6+/-2.2 J x kg(-1) x m(-1),
      36.8+/-4.5 J x kg(-1) x m(-1) and 13+/-2.3 J x kg(-1) x m(-1) in the HTS. TLim-v
      VO2max was inversely related to C(slope) (r = -0.77, P < 0.001), and to v VO2max
      (r = -0.35, P = 0.05), although no relationships with the Cv VO2max and the
      C(inc) were observed. CONCLUSIONS: The findings of this study confirmed exercise
      economy as an important factor for swimming performance. The data demonstrated
      that the swimmers with higher and v VO2max performed shorter time in TLim-v
      VO2max efforts.

PMID- 16998441
TI  - Comparison of force-time parameters and EMG in static explosive gripping by
      various exertion conditions: muscle fatigue state and submaximal exertion.
AB  - AIM: The purpose of this study was to compare the exertion and electromyography
      (EMG) properties during the developmental phase (DFmax) in static explosive grip
      (SEG), rapid submaximal exertion grip, namely fake SEG exertion (FAKE), and SEG
      in a muscle fatigue state. METHODS: Thirty healthy males and females performed
      the SEG and FAKE exertions (50% and 75% of peak value as a target value). Then,
      they performed sustained repeated rhythmic grip for 6 min (30 times x min(-1)),
      and SEG after 1-min, 4-min, and 7-min (SEG after the exertion). EMG was measured
      concurrently to compare with the muscle activation property during each grip
      exertion. Eight force-time parameters evaluating the DFmax in addition to the
      peak value were selected. RESULTS: The peak value significantly decreased, and
      the mean power spectrum density shifted to the low-wave in SEG after the exertion
      as compared with before. Therefore, SEG after the exertion was judged to be a
      muscle fatigue state. In addition, because the frequency properties in each
      exertion differed, the muscle activation properties during their DFmaxs were
      considered to differ. From the comparison between SEG before and after the
      exertion and FAKE, it is suggested that the time of reaching the peak value and
      the relative muscle strength when reaching an inflection point are not useful as
      parameters to evaluate the explosive muscle function during SEG. CONCLUSIONS: The
      maximal increasing volume during the DFmax and integrated area until 0.25 and 0.5
      s could discriminate a difference of the DFmaxs according to each exertion and
      they are useful parameters.

PMID- 16998442
TI  - Reproducibility of variables derived from a 90 s all-out effort isokinetic
      cycling test.
AB  - AIM: The aim of this study was to examine the reliability of the power output
      profile obtained from a 90 s all-out isokinetic cycling test. METHODS: Within a
      10 day period, 16 participants (-x+/-s: age 30.1+/-6.4 years; body mass 69.2+/
      10.6 kg) performed an incremental VO2 max ramp test and two 90 s all-out efforts
      on an isokinetic cycle ergometer. Peak power (PP), mean power (MP), end power
      (EP) and fatigue index (FI) were determined. RESULTS: There were no significant
      differences between tests for MP, EP and FI values (P > 0.05) but PP was higher
      on the second test (P = 0.003). Ratio limits of agreement suggested that a
      repeated measurement might be expected in 95% of cases to be between 0.92 to 1.21
      times the initial PP measurement and 0.97 to 1.07 times the initial MP
      measurement. The 95% limits of agreement for EP and fatigue were -23 to +33 W
      (1.8+/-9.7% of the mean) and -6.5% to 8.8% (2+/-7.6% of the mean), respectively.
      CONCLUSIONS: The 90 s all-out test appears to be a reliable test for given
      aspects of the physiological profile, with the exception of PP.

PMID- 16998443
TI  - Performance during consecutive days of laboratory time-trials in young and
      veteran cyclists.
AB  - AIM: There is a common belief amongst athletes and coaches that older athletes
      need longer recovery time between training sessions and following competition.
      This study was undertaken to investigate the influence of age on recovery from
      high intensity endurance exercise in well-trained cyclists. METHODS: Nine young
      and 9 veteran cyclists (mean+/-SD: young 24+/-5 years, veteran 45+/-6 years)
      performed 3 consecutive days (T1-T3) of laboratory based cycling time trials of
      30-min duration (TT30). Mean power output, heart rate (HR), and blood lactate
      were measured throughout each TT30. Non-specific performance tests of fatigue
      were undertaken before and after the TT30 on each test day. Non-specific tests
      included, a maximal voluntary isometric contraction of the quadriceps muscle
      (MVIF), a countermovement jump (CMJ), a 10-s cycle sprint (10ST), and serum
      creatine kinase activity (CK). RESULTS: Statistical analysis revealed that there
      were no significant group differences between young and veteran subjects for
      initial fitness or training status. Over T1-T3 both groups maintained average
      power during the TT30 (young and veteran results combined; 3.49+/-0.38, 3.5+/
      0.36 and 3.52+/-0.35 W x kg(-1), T1-T3, respectively). For both groups serum CK
      activity was significantly elevated at T2 and T3, and mean HR during the TT30 was
      significantly lower at T3 (approximately 3 b x min(-1)). There were no group
      differences or significant within group interactions across the 3 days for MVIF
      or 10ST but there was a significantly lower CMJ height by T3 in both young and
      veteran (approximately 3%). MVIF was significantly lower after TT30 each day but
      had fully recovered by the following day. CONCLUSIONS: These findings suggest
      that high-intensity endurance performance is maintained in both well-trained
      young and veteran cyclists following 3 consecutive days of maximal 30-min
      laboratory time trials.

PMID- 16998444
TI  - Effects of static stretching volume and intensity on plantar flexor explosive
      force production and range of motion.
AB  - AIM: The aim of the study was to determine the effects of volume and intensity of
      static stretching in a warm-up on explosive force production and range of motion
      (ROM) of the plantar flexors. METHODS: Twenty subjects performed 5 warm-ups on
      different days. The warm-ups contained a 5 min treadmill run and various
      protocols of 30 s static stretches (SS) of the plantar flexors. Stretching
      involved dorsi flexion just before the pain threshold, which was considered 100%
      intensity. The treatments that immediately followed the run were: (i) no other
      treatment (control); (ii) 1 min SS; (iii) 2 min SS; (iv) 4 min SS; (v) 2 min SS
      at 90% intensity. Ankle ROM was assessed before and after each warm-up and a
      concentric calf raise and drop jump (DJ) test was conducted after each warm-up.
      RESULTS: There were no significant differences (P > 0.05) in peak force or rate
      of force production in the explosive calf raise between any of the warm-ups.
      However the run plus 2 min stretch and the run plus 4 min stretch protocols
      produced significantly lower (P < 0.05) DJ performance (jump height/ground
      contact time) than the run. The run plus 4 min stretch warm-up also produced a
      significantly lower DJ score than the run plus 1 min stretch warm-up. There were
      no significant differences between any of the warm-ups in ankle ROM. CONCLUSIONS:
      The addition of 2-4 min of SS at 100% intensity to a run caused an impairment to
      fast stretch shortening cycle muscle performance. The greater impairment from the
      4 min stretching condition supported a volume-effect. Two minutes of stretching
      at 90% intensity had no significant influence on muscle function. The addition of
      up to 4 min of SS to a run had no appreciable effect on ankle ROM, possibly
      because of the prior influence of the run.

PMID- 16998445
TI  - Aerobic fitness and somatic growth in adolescents: a cross sectional
      investigation in a high school context.
AB  - AIM: A cross-sectional investigation to study the relations between aerobic
      fitness and somatic growth of Italian adolescents within a school context.
      METHODS: The Leger and Lambert 20-m shuttle run test scores were used to estimate
      the oxygen uptake (VO2max) of 290 high school adolescent students aged 14-18
      years. Descriptive statistics of body mass, standing height, body mass index
      (BMI) and of predicted VO2max were calculated within age and sex group. RESULTS:
      Body mass and standing height were significantly larger in males than in females,
      and significantly increased with age (P < 0.002, analysis of variance). For
      standing height, a significant sex age interaction was found (P = 0.0004), with a
      larger age-related increment in males than in females. No significant differences
      in BMI were found. VO2max was significantly influenced by sex and age. The age
      related decrement in VO2max was larger in females than in males (P = 0.001).
      Predicted VO2max was significantly related to BMI (males: r = -0.41; females: r =
      -0.336) and to body mass (females: r = -0.34; males: r = -0.352). A negative
      relationship between BMI and VO2max was found also in the overweight adolescents.
      CONCLUSIONS: In both sexes, aerobic fitness declined with age. The decline was
      particularly evident in females. Low-cost methods to detect the nutritional level
      and aerobic performance of adolescents should be encouraged at school.

PMID- 16998446
TI  - Assessment of power output in jump tests for applicants to a sports sciences
      degree.
AB  - AIM: Our study aimed: 1) to describe the jump performance in a population of male
      applicants to a Faculty of Sports Sciences, 2) to apply different power equations
      from the literature to assess their accuracy, and 3) to develop a new regression
      equation from this population. METHODS: The push off phases of the counter
      movement jumps (CMJ) on a force platform of 161 applicants (age: 19+/-2.9 years;
      weight: 70.4+/-8.3 kg) to a Spanish Faculty of Sports Sciences were recorded and
      subsequently analyzed. Their hands had to be placed on the hips and the knee
      angle during the counter movement was not controlled. Each subject had 2 trials
      to reach a minimum of 29 cm of jump height, and when 2 jumps were performed the
      best trial was analyzed. Multiple regression analysis was performed to develop a
      new regression equation. RESULTS: Mean jump height was 34.6+/-4.3 cm, peak
      vertical force 1 663.9+/-291.1 N and peak power 3524.4+/-562 W. All the equations
      underestimated power, from 74% (Lewis) to 8% (Sayers). However, there were high
      and significant correlations between peak power measured on the force platform,
      and those assessed by the equations. CONCLUSIONS: The results of the present
      study support the development of power equations for specific populations, to
      achieve more accurate assessments. The power equation from this study [Power =
      (62.5 x jump height (cm)) + (50.3 x body mass (kg)) 2184.7] can be used
      accurately in populations of male physical education students.

PMID- 16998447
TI  - Effects of music during exercise on RPE, heart rate and the autonomic nervous
      system.
AB  - AIM: The purpose of this study was to investigate the relationship between the
      influence of music on RPE during sub-maximal exercise and on the autonomic
      nervous system before and after sub-maximal exercise. METHODS: Heart rate (HR),
      HR variability (HRV) and rates of physical fatigue (RPE) during exercise at 60%
      and at 40% VO2max with and without music were measured. The exercise protocol
      consisted of a 30-min seated rest (control) period followed by a 30-min
      submaximal cycling exercise and a 35-min recovery period. Autonomic-nervous
      activity was measured before and after exercise. During exercise, RPE was
      recorded every 3 min and HR was recorded for every minute. RESULTS: Although RPE
      did not differ during exercise at 60% VO2max, this value was lower during
      exercise at 40% VO2max in the presence, than in the absence of a favorite piece
      music (P < 0.05). HR, HFA and LFA/HFA of HRV significantly differed with exercise
      intensity in the absence (P < 0.05), but not in the presence of music.
      CONCLUSIONS: These findings suggested that music evokes a ''distraction effect''
      during low intensity exercise, but might not influence the autonomic nervous
      system. Therefore, when jogging or walking at comparatively low exercise
      intensity, listening to a favorite piece of music might decrease the influence of
      stress caused by fatigue, thus increasing the ''comfort'' level of performing the
      exercise.

PMID- 16998448
TI  - Effect of age on metabolic fatigue and on indirect symptoms of skeletal muscle
      damage after stretch-shortening exercise.
AB  - AIM: The purpose of this study was to establish the main differences between men
      (M) and adolescents (A) (males) in metabolic fatigue and damage induced by
      exercise performed at maximal intensity. METHODS: Healthy A (age 13.4 0.6 years,
      n = 12) and healthy adult M (age 25.4 1.7 years, n = 12) participated in this
      study. To induce muscle damage and metabolic fatigue stretch-shortening exercise
      (SSE) (5 bouts of 20 jumps with counter-movement to 90 degrees angle in the knee
      with 10 s between bouts) has been chosen. The following data were measured: the
      force of the quadriceps muscle, aroused by electrical stimulation at different
      frequencies, maximal voluntary contraction force, height of jump (JH), muscle
      soreness, lactate (La) concentration and creatine kinase (CK) activity in the
      blood. All the parameters mentioned were measured before exercise and 2-5 min, 20
      min, 24 h and 48 h after the SSE, except for La concentration changes in the
      blood measured before exercise, 2 min and 20 min after the SSE. RESULTS: The main
      findings in this study are the following: 1) during SSE JH decreased
      significantly (P < 0.05) more in M than in A, whereas La concentration in the
      blood after SSE increased more in M than in A; 2) indirect symptoms of muscle
      damage were more evident in M than in A; 3) there was secondary decrease in
      electrically induced muscle force at 10-20 Hz from 3 min until 20 min after SSE
      but only in the muscles of M; 4) low frequency fatigue after SSE was more evident
      in M than A. CONCLUSIONS: The results of the present study indicate that the
      muscles of adolescents are more resistant to both metabolic fatigue and exercise
      induced damage than those of men.

PMID- 16998449
TI  - Estimation of body fat in athletes: skinfolds vs bioelectrical impedance.
AB  - AIM: The aim of the present study was to compare two different field methods
      (skinfolds(SKF(vs bioimpedance analysis(BIA) for estimation of body fatness in
      top-level athletes. METHODS: This study was conducted with 219 male professional
      athletes who were recruited during pre-participation physical examination.
      Skinfold thicknesses at 7 sites were obtained using a Harpenden caliper while
      total body resistance was measured with a foot-pad bioelectrical impedance
      analyzer at a fixed signal frequency of 50 kHz and 500 microA. RESULTS: The
      athletes showed non-significant difference in body fat percentage (%BF) between
      the average %BFSKF and %BFBIA (P > 0.05). Average time of assessment per subject
      was significantly longer during skinfold measurement (P < 0.01) as compared with
      BIA assessment. CONCLUSIONS: We found that the estimates of body fat were similar
      between SKF and BIA with significant correlation (r = 0.96) between methods while
      BIA method is less time-consuming. In conclusion, the most simple, quick, and
      inexpensive method of BIA seems to be very useful to the dietitians' routine for
      assessing body fat in physically active individuals and athletes.

PMID- 16998450
TI  - Validity of foot-to-foot bioelectrical impedance analysis in overweight and obese
      children and parents.
AB  - AIM: The aim of this study was to evaluate the validity of foot-to-foot
      bioelectrical impedance analysis (FF-BIA) in the measurement of body composition
      in overweight and obese children and their parents by comparison to dual-energy X
      ray absorptiometry (DXA). METHODS: Seventeen, 7-12 year old overweight and obese
      children (6 boys, 11 girls) and 17 parents (5 fathers, 12 mothers) were evaluated
      for body composition with FF-BIA and DXA. Measures of percent body fat (PBF), fat
      mass (FM) and fat free mass (FFM) derived from FF-BIA and DXA were compared.
      Measures of validity were determined by Pearson correlations between FF-BIA and
      DXA, paired t-tests to assess mean differences, as well as biases and limits of
      agreement using the Bland Altman tests. RESULTS: FF-BIA produced estimates of
      body composition that were highly correlated with DXA in overweight and obese
      children and parents. For children, the correlations for PBF, FM, and FFM were
      0.85, 0.97, and 0.94, respectively. For parents, the correlations for PBF, FM,
      and FFM were 0.92, 0.97, and 0.91, respectively. However, mean differences
      between FF-BIA and DXA were significant in children but not in parents. Bland
      Altman tests of agreement showed moderate to large within-subject differences in
      body composition variables between FF-BIA and DXA. CONCLUSIONS: FF-BIA is
      strongly related to DXA in the measurement of body composition in both overweight
      and obese preadolescent children and parents, but the two measures may not be
      used interchangeably. Although FF-BIA may lack the precision to assess small
      changes in body composition in overweight and obese individuals, it is
      appropriate for epidemiological use.

PMID- 16998451
TI  - Effect of a maximal treadmill test on percent body fat using leg-to-leg
      bioelectrical impedance analysis in children.
AB  - AIM: The purpose of this investigation was to determine the effect of a maximal
      treadmill exercise test on percent body fat (%BF) in children using leg-to-leg
      bioelectrical impedance analysis (LBIA) (Tanita Model #TBF-300A). METHODS: Fifty
      four children (24 females; 30 males) between 7-10 years of age participated in
      this study. LBIA measures of %BF were obtained immediately before and within 5
      min after completing a maximal oxygen consumption test on a motorized treadmill.
      RESULTS: No pre- to post-test differences in %BF were observed in either group
      (mean difference: females 1.6%, males 1.5%). Impedance values significantly
      decreased postexercise (P < 0.05) in the female subjects. No significant
      differences were observed for fat mass, fat free mass, total body water or body
      weight postexercise when compared to pre-exercise values in either group.
      Correlations (P = 0.0001) of 0.997 were observed between pre- and postexercise
      measures of %BF. CONCLUSIONS: A maximal treadmill exercise test conducted prior
      to LBIA has no impact on %BF in children. Therefore, normal daily activities
      performed prior to LBIA assessment may have a limited impact on LBIA body
      composition measurement in children. As such, compliance with stringent
      pretesting exercise guidelines may not be essential when using LBIA to assess %BF
      in children.

PMID- 16998452
TI  - Effects of vitamin E supplementation on oxidative stress at rest and after
      exercise to exhaustion in athletic students.
AB  - AIM: The purpose of this study is to determine the effect following exercise to
      exhaustion of vitamin E supplementation on oxidative stress in athletic students.
      METHODS: Twenty male students voluntarily participated in the study and were
      randomly assigned (double blind) to either a vitamin E (daily dose of 450 mg of a
      tocopherol for a period of 8 weeks) or a placebo group (took capsules containing
      450 mg of lactose for 8 weeks). Before and after 8 weeks blood samples were
      collected at rest and after exercise to exhaustion. Oxidative stress markers were
      malondialdehyde (MDA), carbonylated proteins (CP) and creatine kinase (CK). Also,
      the effect of vitamin E on ergometer cycling time, as an example of endurance
      performance, was evaluated. RESULTS: ANOVA and independent t-tests indicated that
      vitamin E supplementation did not significantly change (P > 0.05) MDA, CP and CK
      values at rest, after exercise to exhaustion, and cycling time, but plasma volume
      after exercise to exhaustion significantly decreased (P < 0.05). CONCLUSIONS:
      Although vitamin E supplementation had no effect on exercise performance or
      capacity in athletic students, further investigation is required using larger
      numbers of subjects and measures of vitamin E before unequivocal conclusion can
      be stated.

PMID- 16998453
TI  - The effects of vitamin C supplementation on symptoms of delayed onset muscle
      soreness.
AB  - AIM: The aim of this study was to compare the effects of 8 days of vitamin C (VC)
      supplementation on elbow flexor delayed onset muscle soreness (DOMS) to 8 days of
      placebo ingestion. METHODS: For 3 days prior to an exercise bout (2 x 20
      eccentric elbow extensions), and for 5 days after, a treatment group ingested 3 x
      1000 mg/day of VC versus 3 x 50 mg/day of glucose ingestion for the placebo group
      over the same time period. All subjects were prescreened via dietary recall to
      exclude any subjects with habitual VC consumption greater than 400 mg/day.
      Subject comprised 24 subjects (male and female) randomly divided into 2 groups of
      12 subjects. Treatment group comprised 5 females and placebo group comprised 8
      females. RESULTS: Data from a repeated measures ANOVA indicate that DOMS was
      successfully induced in both groups via significant time effects for strength
      loss (P = 0.0001), point tenderness (P = 0.0001), elbow flexor decreased range of
      motion (P = 0.013), and subjective pain (P = 0.0001). However, there were no
      significant between group differences in response to any of the aforementioned
      variables: strength loss (P = 0.202), point tenderness (P = 0.824), elbow flexor
      range of motion (P = 0.208), subjective pain (P = 0.342). CONCLUSIONS: The
      results of this study suggest that a VC supplementation protocol of 3 x 1000
      mg/day for 8 days is ineffective in protecting against selected markers of DOMS.

PMID- 16998454
TI  - The ischiatic region: normal and MRI anatomy.
AB  - AIM: The aim of this study was to describe the anatomy correlated to the normal
      magnetic resonance imaging (MRI) images of the proximal thigh region and the
      ischial tuberosity. METHODS: MRI coronal and axial sequences were obtained from
      20 asymptomatic volunteers (10 male and 10 female) aged 20 to 38 years (mean age:
      28 years), and then they were compared with 2 anatomical dissections and 7
      cryosections of 6 cadaver thighs. RESULTS: The anatomical specimens were directly
      correlated with MRI scans. From the comparison it could be seen how the axial MRI
      sequences well outlined the sciatic nerve, usually observed oval in shape with
      moderate signal intensity, and thus easily detectable from other surrounding
      organs. Other structures were also identified by axial images: the ischial
      tuberosity, the proximal origin of the hamstring muscles arising from the ischium
      and the related bursae, the gluteus maximus and its bursa, the quadratus femoris
      and its inconstant bursa, a triangular adipose body and vessels. Coronal scans
      also showed well the hamstring muscles, both in length and thickness.
      CONCLUSIONS: Both MRI images and cadaver dissections showed the ischial
      tuberosity as an interesting intersection area that could be delimited as
      follows: on the dorsal border the gluteus maximus and its bursa, on the dorso
      medial side the hamstring muscle origin, and on the antero-lateral side the
      quadratus femoris muscle with its inconstant bursa and the ischial tuberosity.
      These anatomical and MRI descriptions are very useful to give a contribution to
      the right explanation of sciatic symptoms caused by those sports specifically
      overloading the hamstring muscles. Frequently, in fact, in these athletes a
      sciatic syndrome arise drawing the physician's attention to the lumbosacral joint
      or to the sciatic nerve course near the piriformis muscle. Another very important
      site where the sciatic symptoms can rise, indeed, could also be found in the
      hamstring muscle region, where the nerve run under the gluteus maximus beside the
      ischiatic bone. Athletes who manifest notorious muscle overload in this
      anatomical region usually show sciatic pain symptoms that are not to be related
      with pathologies of the lumbosacral junction nor to relationships of the sciatic
      nerve with the piriformis muscle but rather to relationships that this nerve
      acquires with either gluteal muscles as well as with muscles of the underneath
      ischiatic region.

PMID- 16998455
TI  - Non-union of the clavicle and delayed union of the proximal fifth metatarsal
      treated with low-intensity pulsed ultrasound in two soccer players.
AB  - Operative treatment has become the treatment of choice in athletes and active
      patients in non-union of the clavicle and delayed union of the proximal fifth
      metatarsal. The purpose of this study was to review the short- and long-term
      clinical results of low-intensity pulsed ultrasound treatment in a non-union of
      the clavicle and in a delayed union of the proximal fifth metatarsal in 2 elite
      soccer players. In both patients, the treatment sessions were performed with an
      ultrasound signal that was composed of a burst width of 200+/-10% mus containing
      1.5+/-5% MHz sine waves, with a repeating rate of 1+/-10% kHz and a spatial
      average temporal intensity of 30+/-30% mW/cm2. The application of the ultrasound
      was performed by the patients at home for 20 min/day for 3 months. The healing of
      the non-union of the clavicle was followed by MR imaging and of the delayed union
      of the proximal fifth metatarsal by radiographs. In both of the cases the end
      results were excellent and the players could continue playing at the highest
      level. The ultrasound method was successful and afforded players a quick return
      to sport activity.

PMID- 16998456
TI  - Changes in serum cardiac troponins following a 21-km run in junior male runners.
AB  - AIM: This study was designed to examine the appearance and clearance
      characteristics of serum cardiac troponin T (cTnT) and I (cTnI) in junior runners
      after an exhaustive 21-km run. The dependence of the alternations of the cardiac
      troponins on the runners' training status reflected in training years, running
      ability and physiological profile at ventilatory threshold (Th(vent)) was also
      examined. METHODS: Ten trained male adolescents (16.2+/-0.6 years) performed 21
      km run and graded treadmill exercise with maximum effort on two different days.
      cTnT and cTnI immediately before and 2, 4 and 24 hours after exercise were
      measured in the 21-km trial. The parameters at Thvent including the running speed
      (Th(vent)-Speed) and VO2 (Th(vent)-VO2) were identified in the graded exercise
      trial. RESULTS: Serum cTnT and cTnI in 6 of the 10 subjects measured 4 hours
      after the 21-km run were above the myocardial injury cutoffs of 0.03 and 0.09 ng
      x mL(-1), respectively, but returned towards pre-exercise levels within 24 hours
      that were not in the same manner observed in the clinical situation of myocardial
      infraction. The 6 subjects' training status was generally lower than that of the
      rest 4. Further, subjects' 4-h serum cTnT and cTnI were negatively related to
      their training years, Th(vent)-Speed and Th(vent)-VO2, and positively related to
      their personal best in half- and full-marathon races (r2 = or > 36%, n = 10).
      CONCLUSIONS: Such findings implied that clinicians based the diagnosis of long
      distance run-induced myocardial infraction in novice junior runners upon the
      transient postexercise elevations of cardiac troponins alone should be with
      caution.

PMID- 16998457
TI  - Extreme mountain bike challenges may induce sub-clinical myocardial damage.
AB  - AIM: The relationship between extreme exercise and coronary artery disease is not
      well understood, and the information available is contradictory. The aim of the
      present study was to determine whether strenuous endurance exercise, performed
      under conditions in which the partial pressure of environmental oxygen varies
      constantly, can induce myocardial cell injury. METHODS: Plasma urea, creatinine,
      creatine kinase, myoglobin and cardiac troponin I (cTnI) concentrations were
      measured the day before and immediately after a mountain bike challenge (distance
      95 km, cumulative altitude difference 2340 m) in eleven amateur male cyclists.
      RESULTS: All biochemical markers of muscle cell damage increased significantly
      after exercise. Although cTnI concentrations also increased significantly, they
      remained below the threshold (0.5 microg/L) indicative of acute myocardial
      infarction. CONCLUSIONS: In male, amateur mountain bikers, this kind of strenuous
      exercise may induce sub-clinical myocardial injury.

PMID- 16998458
TI  - Effects of the training status on the hormonal response and recovery from high
      intensity isokinetic exercise: comparisons between endurance-trained athletes and
      sedentary subjects.
AB  - AIM: Aims of the study were: to determine the differences in the mechanical,
      hormonal and lactate responses to a high-intensity isokinetic exercise in two
      groups of endurance-trained athletes (EA, n = 11) and sedentary subjects (SED, n
      = 11); to evaluate the relationships between the hormonal and lactate responses;
      to evaluate the effects of the training status on the pituitary responsiveness to
      the exercise. METHODS: EA and SED completed, for each leg, 4 sets of 20 maximal
      concentric contractions of the knee extensor muscle groups at 180 degrees s-1
      angular velocity. Blood and saliva for hormonal and lactate determinations were
      sampled before, immediately after the test and during the subsequent recovery of
      2 hours. RESULTS: The exercise was completed by all subjects and elicited
      significant mechanical and biochemical responses both in EA and in SED subjects.
      No differences were found between the two groups both in the mechanical
      performances and in the increases of lactate and hormones of the pituitary
      adrenal axis or in the comparison of the slopes of adrenocorticotropic hormone
      (ACTH), cortisol, and dehydroepiandrosterone recovery after the peak. The
      correlation analyses showed significant positive relationships between lactate
      peak values and percentages of change for ACTH (r2 = 0.16, P < 0.05), salivary
      cortisol (r2 = 0.42, P < 0.01), and serum cortisol (r2 = 0.56, P < 0.001).
      CONCLUSIONS: The adrenocortical activation was found, in this particular setting,
      at least partly dependent on the muscular lactate production, while no effect of
      the training status on the pituitary responsiveness to exercise was evident, as
      it was indirectly confirmed by no abnormalities in the rates of hormonal recovery
      after the exercise session.

PMID- 16998459
TI  - Frequency and direction of competitive anger in contact sports.
AB  - AIM: The purpose of the present study was to investigate whether athletes
      involved in physical contact sports may interpret their feelings of anger as
      facilitative of performance, and to examine differences in the interpretation of
      anger as a function of the type of sport (team vs individual) or the competitive
      skill level (high vs low). METHODS: A modified version of the State-Trait Anger
      Expression Inventory was administered to 100 Italian adult male athletes
      practicing rugby or individual combat sports (judo, freestyle wrestling, or Greco
      Roman wrestling). The questionnaire was intended to measure the frequency and the
      direction (i.e., the facilitative-debilitative interpretation) of competitive
      anger. RESULTS: Many athletes engaged in contact sports tended interpret their
      competitive anger as facilitative of performance rather than debilitative. The
      type of sport and the athlete's standard level can mediate the individual's
      interpretation of the effects of anger symptoms upon performance. CONCLUSIONS:
      Competitors can interpret their anger as helpful to energize behavior and channel
      physical and mental resources for skill execution. Practitioners should assist
      athletes in gaining control over anger rather than attempting to suppress it.

PMID- 16998460
TI  - The angiotensin converting enzyme I/D polymorphism in long distance runners.
AB  - AIM: There is an assumption that ACE I/D polymorphism represents one of the
      possible genetic factors that might be associated with sports excellence. Recent
      studies have identified an increased frequency of I allele in elite endurance
      athletes, long distance runners, rowers and mountaineers. The aim of this study
      was to test the hypothesis that the ACE I/D polymorphism is associated with
      enhanced endurance performance. METHODS: We examined this hypothesis by
      determining ACE I/D allele frequency in 215 marathon runners, 222 half-marathon
      runners and 18 inline skaters classified by performance (marathon competition
      results). ACE genotype and allele frequencies were compared with 252 healthy
      controls. RESULTS: ACE genotype frequency in the whole cohort did not differ from
      that in the sedentary controls (P < 0.56). However, there was an increase of the
      I/I genotype incidence amongst successful marathon runners scoring on places from
      1st to 150th (P < 0.01). These findings were confirmed in the group of inline
      skaters, similarly demonstrating an increase of the I/I genotype (P < 0.01).
      There was no association found between half marathon runners and the ACE genotype
      (P < 0.59). CONCLUSIONS: An excess of the I allele in long distance runners
      confirms the association between the ACE I/D polymorphism and endurance sports
      performance.

PMID- 16998461
TI  - Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: Utility
      of HBME1 combined with CK19 immunostaining.
AB  - Papillary thyroid carcinoma and its variants can be difficult to distinguish from
      cellular adenomatous nodules. Prior studies have advocated various antibodies to
      aid in the differential diagnosis, but there is little agreement on their
      utility. We undertook this study to evaluate immunohistochemical markers in the
      diagnosis and differential diagnosis of papillary thyroid carcinoma. Ten cases of
      papillary thyroid carcinoma were initially stained for HBME1, CK19, fibronectin1,
      Ki-67, Calretinin, p16, SFTPB and CITED1. Additionally, two previously untested
      antibodies to molecules that have been found to be upregulated in papillary
      thyroid carcinoma (CST6 and EPS8) were also evaluated. Of these, only HBME1, CK19
      and fibronectin1 showed diagnostic utility. These three markers were then further
      evaluated in 51 papillary thyroid carcinomas and 57 benign thyroids. HBME1 was
      the most sensitive and specific marker, staining 49/51 papillary thyroid
      carcinomas and only 4/57 benign thyroids. CK19 was equally sensitive staining all
      51 papillary thyroid carcinomas, but it was nonspecific staining 39 of 57 benign
      thyroids. A negative result, however, was helpful in excluding papillary thyroid
      carcinoma. Fibronectin1 was positive in 35/51 papillary thyroid carcinomas (69%)
      and 4/57 (7%) benign thyroids, but its utility was hampered by high background
      staining. These findings suggest that the combination of HBME1 and CK19 has the
      greatest diagnostic utility in the differentiation of papillary thyroid carcinoma
      from its benign mimics.

PMID- 16998462
TI  - Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell
      myeloma, and acute lymphoblastic leukemia.
AB  - SALL4, a newly identified zinc-finger transcriptional factor important for
      embryonic development, is mapped to chromosome 20q13. Previously, we reported
      that SALL4 was constitutively expressed in acute myeloid leukemia and SALL4
      transgenic mice developed acute myeloid leukemia. In this study, we aimed to
      survey SALL4 protein expression in benign and neoplastic hematopoietic tissues in
      addition to acute myeloid leukemia using immunostaining with a polyclonal anti
      SALL4 antibody. Primary hematological tumors (178) and 15 benign hematopoietic
      tissues were examined. Reverse transcription-polymerase chain reaction was also
      performed to detect SALL4 mRNA expression on eight precursor B-cell lymphoblastic
      leukemia/lymphomas, 10 benign hematopoietic tissues, and seven hematopoietic
      cancer cell lines. Of the benign tissues, SALL4 expression was detectable only in
      CD34+ hematopoietic stem/progenitor cells (2/2 at protein level, 3/3 at RNA
      level). In neoplastic tissues, only precursor B-cell lymphoblastic
      leukemia/lymphomas had detectable SALL4 (12/16 at protein level, 7/8 at RNA
      level), similar to that observed in acute myeloid leukemia. Of the seven cell
      lines examined, only those derived from acute myeloid leukemia and precursor B
      cell lymphoblastic leukemia/lymphomas were positive. To conclude, SALL4
      expression is normally restricted to CD34+ hematopoietic stem/progenitor cells.
      The persistence of SALL4 expression in leukemic blasts in precursor B-cell
      lymphoblastic leukemia/lymphomas resembles to what we observed in acute myeloid
      leukemia, and correlates with the maturation arrest of these cells. We have shown
      in our previous study that the constitutive expression of SALL4 in mice can lead
      to acute myeloid leukemia development. The similar expression pattern of SALL4 in
      acute myeloid leukemia and B-cell lymphoblastic leukemia/lymphomas suggests that
      these two disease entities may share similar biological features and/or
      mechanisms of leukemogenesis. More definite studies to investigate the role of
      SALL4 in the pathogenesis of B-cell lymphoblastic leukemia/lymphomas are needed
      in the future to address this question.

PMID- 16998463
TI  - Primary testicular diffuse large B-cell lymphoma belongs to the nongerminal
      center B-cell-like subgroup: A study of 18 cases.
AB  - The most common type of primary testicular lymphoma is diffuse large B-cell type,
      which has the potential for aggressive clinical behavior. Diffuse large B-cell
      lymphoma can be further subclassified into two major prognostic categories:
      germinal center B-cell-like and nongerminal center B-cell-like. Such distinction
      is made possible using the immunohistochemical expression of CD10, Bcl-6 and
      MUM1. The aim of this study was to stratify primary testicular lymphoma of the
      diffuse large B-cell type according to this scheme. Immunohistochemical stains
      for CD10, Bcl-6 and MUM1 were performed on 18 cases of primary testicular
      lymphoma of diffuse large B-cell type. Subclassification was carried out as
      previously described where CD10 and/or Bcl-6 positivity and negativity for MUM1
      were considered indicative of germinal center B-cell-like type and the opposite
      expression as nongerminal center B-cell-like type. The proliferative activity was
      determined using immunostaining with the Ki-67 antibody. Of 18 cases, 16 (89%)
      were found to belong to the nongerminal center B-cell-like type. Two cases (11%)
      were classified as germinal center B-cell-like type; one had a CD10-positive, Bcl
      6-positive and MUM1-negative profile, and the other was CD10 negative, Bcl-6
      positive and MUM1 negative. The former occurred in a 38-year-old patient who was
      human immunodeficiency virus positive. All the cases expressed high proliferative
      activity (> or =50% Ki-67 labeling). We conclude that most (89%) primary
      testicular lymphomas of the diffuse large B-cell type belong to the nongerminal
      center B-cell-like subgroup and have high proliferative activity.

PMID- 16998464
TI  - Downregulation of BRG-1 repressed expression of CD44s in cervical neuroendocrine
      carcinoma and adenocarcinoma.
AB  - Neuroendocrine carcinomas of the uterine cervix are rare tumors with early
      metastases, highly aggressive clinical behavior, and poor clinical outcome.
      Several adhesion molecules like cadherins have been tested in an attempt to
      explain their unique characteristics. Cluster differentiation 44 (CD44) is a
      widely expressed cell surface glycoprotein that serves as an adhesion molecule in
      cell-to-substrate and cell-to-cell interaction. We have examined the expression
      of the standard CD44 (CD44s) by immunohistochemical stains in the paraffin
      embedded cervical neoplasm tissue of 17 cases of primary cervical neuroendocrine
      carcinoma, 28 cases of cervical adenocarcinoma, and 50 cases of cervical squamous
      cell carcinoma. Loss of CD44s expression was found in 16 of 17 neuroendocrine
      carcinomas, 14 of 28 adenocarcinomas, and three of 50 squamous cell carcinomas.
      The differences were statistically significant. We also examined
      immunohistochemically the expression of the BRG-1 subunit of the SWI-SNF complex,
      which has been reported to regulate the expression of CD44 in all cases. Loss of
      BRG-1 expression was observed in 12/16, 6/14, and 1/3 CD44s-negative
      neuroendocrine carcinomas, adenocarcinomas, and squamous cell carcinomas,
      respectively. This study suggests that loss of the CD44s molecule may imply
      special biological behaviors of cervical neuroendocrine carcinomas, and loss of
      expression of BRG-1 may contribute to this.

PMID- 16998465
TI  - Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum
      of maturation among CD4+ CD56+ hematodermic neoplasms.
AB  - CD4+CD56+ hematodermic neoplasms are rare, aggressive hematopoietic malignancies
      usually presenting with cutaneous masses followed by a leukemic phase. The
      blastic morphology, CD56 expression and lack of definitive myeloid or T-cell
      markers initially resulted in assignment of this tumor to the NK-cell lineage.
      Accumulating evidence now suggests that these neoplasms represent malignant
      counterparts to the plasmacytoid dendritic cell. BDCA-2 is a cell surface protein
      whose expression is restricted to human plasmacytoid dendritic cells, in a
      differentiation stage-specific manner. In the current study, we assessed
      expression of BDCA-2 in CD4+CD56+ hematodermic neoplasms using a new antibody
      reagent we developed for use in fixed tissue sections. In 10 of 19 cases of
      CD4+CD56+ hematodermic neoplasm, BDCA-2 immunoreactivity was detected, whereas no
      expression was observed in NK-lineage tumors (0 of six). Interestingly,
      expression of terminal deoxynucleotidyl transferase, a marker of immaturity/blast
      stage, was significantly and negatively correlated with BDCA-2 in CD4+CD56+
      hematodermic neoplasms whereas a positive correlation was observed between BDCA-2
      and CD7. These findings demonstrate that BDCA-2 is expressed predominantly in the
      CD7+ subset of hematodermic neoplasms, and similar to non-neoplastic plasmacytoid
      dendritic cells, expression indicates a relatively more mature differentiation
      state. Clinical follow-up data confirm the aggressiveness of these tumors and
      suggests that BDCA-2 immunoreactivity, as identified here, may herald a
      significant reduction in survival.

PMID- 16998466
TI  - Bilateral serous retinal detachment as the first manifestation of paroxysmal
      nocturnal haemoglobinuria.

PMID- 16998467
TI  - Globe rupture as a complication of intravitreal injection of triamcinolone.

PMID- 16998469
TI  - Enzyme-catalysed assembly of DNA hydrogel.
AB  - DNA is a remarkable polymer that can be manipulated by a large number of
      molecular tools including enzymes. A variety of geometric objects, periodic
      arrays and nanoscale devices have been constructed. Previously we synthesized
      dendrimer-like DNA and DNA nanobarcodes from branched DNA via ligases. Here we
      report the construction of a hydrogel entirely from branched DNA that are three
      dimensional and can be crosslinked in nature. These DNA hydrogels were
      biocompatible, biodegradable, inexpensive to fabricate and easily moulded into
      desired shapes and sizes. The distinct difference of the DNA hydrogel to other
      bio-inspired hydrogels (including peptide-based, alginate-based and DNA (linear)
      polyacrylamide hydrogels) is that the crosslinking is realized via efficient,
      ligase-mediated reactions. The advantage is that the gelling processes are
      achieved under physiological conditions and the encapsulations are accomplished
      in situ-drugs including proteins and even live mammalian cells can be
      encapsulated in the liquid phase eliminating the drug-loading step and also
      avoiding denaturing conditions. Fine tuning of these hydrogels is easily
      accomplished by adjusting the initial concentrations and types of branched DNA
      monomers, thus allowing the hydrogels to be tailored for specific applications
      such as controlled drug delivery, tissue engineering, 3D cell culture, cell
      transplant therapy and other biomedical applications.

PMID- 16998470
TI  - Electrical control of Forster energy transfer.
AB  - Bringing together compounds of intrinsically different functionality, such as
      inorganic nanostructures and organic molecules, constitutes a particularly
      powerful route to creating novel functional devices with synergetic properties
      found in neither of the constituents. We introduce nanophotonic functional
      elements combining two classes of materials, semiconductor nanocrystals and dyes,
      whose physical nature arises as a superposition of the properties of the
      individual components. The strongly absorbing rod-like nanocrystals focus the
      incident radiation by photopumping the weakly absorbing dye via energy transfer.
      The CdSe/CdS nanorods exhibit a large quantum-confined Stark effect on the single
      particle level, which enables direct control of the spectral resonance between
      donor and acceptor required for nanoscopic Forster-type energy transfer in single
      nanorod-dye couples. With this far-field manipulation of a near-field phenomenon,
      the emission from single dye molecules can be controlled electrically. We propose
      that this effect could lead to the design of single-molecule optoelectronic
      switches providing building blocks for more complex nanophotonic circuitry.

PMID- 16998471
TI  - Co-delivery of drugs and DNA from cationic core-shell nanoparticles self
      assembled from a biodegradable copolymer.
AB  - Non-viral gene-delivery systems are safer to use and easier to produce than viral
      vectors, but their comparatively low transfection efficiency has limited their
      applications. Co-delivery of drugs and DNA has been proposed to enhance gene
      expression or to achieve the synergistic/combined effect of drug and gene
      therapies. Attempts have been made to deliver drugs and DNA simultaneously using
      liposomes. Here we report cationic core-shell nanoparticles that were self
      assembled from a biodegradable amphiphilic copolymer. These nanoparticles offer
      advantages over liposomes, as they are easier to fabricate, and are more readily
      subject to modulation of their size and degree of positive charge. More
      importantly, they achieve high gene-transfection efficiency and the possibility
      of co-delivering drugs and genes to the same cells. Enhanced gene transfection
      with the co-delivery of paclitaxel has been demonstrated by in vitro and in vivo
      studies. In particular, the co-delivery of paclitaxel with an interleukin-12
      encoded plasmid using these nanoparticles suppressed cancer growth more
      efficiently than the delivery of either paclitaxel or the plasmid in a 4T1 mouse
      breast cancer model. Moreover, the co-delivery of paclitaxel with Bcl-2-targeted
      small interfering RNA (siRNA) increased cytotoxicity in MDA-MB-231 human breast
      cancer cells.

PMID- 16998468
TI  - Distinct catalytic and non-catalytic roles of ARGONAUTE4 in RNA-directed DNA
      methylation.
AB  - DNA methylation has important functions in stable, transcriptional gene
      silencing, immobilization of transposable elements and genome organization. In
      Arabidopsis, DNA methylation can be induced by double-stranded RNA through the
      RNA interference (RNAi) pathway, a response known as RNA-directed DNA
      methylation. This requires a specialized set of RNAi components, including
      ARGONAUTE4 (AGO4). Here we show that AGO4 binds to small RNAs including small
      interfering RNAs (siRNAs) originating from transposable and repetitive elements,
      and cleaves target RNA transcripts. Single mutations in the Asp-Asp-His catalytic
      motif of AGO4 do not affect siRNA-binding activity but abolish its catalytic
      potential. siRNA accumulation and non-CpG DNA methylation at some loci require
      the catalytic activity of AGO4, whereas others are less dependent on this
      activity. Our results are consistent with a model in which AGO4 can function at
      target loci through two distinct and separable mechanisms. First, AGO4 can
      recruit components that signal DNA methylation in a manner independent of its
      catalytic activity. Second, AGO4 catalytic activity can be crucial for the
      generation of secondary siRNAs that reinforce its repressive effects.

PMID- 16998472
TI  - Metagenomic analysis of two enhanced biological phosphorus removal (EBPR) sludge
      communities.
AB  - Enhanced biological phosphorus removal (EBPR) is one of the best-studied
      microbially mediated industrial processes because of its ecological and economic
      relevance. Despite this, it is not well understood at the metabolic level. Here
      we present a metagenomic analysis of two lab-scale EBPR sludges dominated by the
      uncultured bacterium, "Candidatus Accumulibacter phosphatis." The analysis sheds
      light on several controversies in EBPR metabolic models and provides hypotheses
      explaining the dominance of A. phosphatis in this habitat, its lifestyle outside
      EBPR and probable cultivation requirements. Comparison of the same species from
      different EBPR sludges highlights recent evolutionary dynamics in the A.
      phosphatis genome that could be linked to mechanisms for environmental
      adaptation. In spite of an apparent lack of phylogenetic overlap in the flanking
      communities of the two sludges studied, common functional themes were found, at
      least one of them complementary to the inferred metabolism of the dominant
      organism. The present study provides a much needed blueprint for a systems-level
      understanding of EBPR and illustrates that metagenomics enables detailed, often
      novel, insights into even well-studied biological systems.

PMID- 16998473
TI  - Compact, universal DNA microarrays to comprehensively determine transcription
      factor binding site specificities.
AB  - Transcription factors (TFs) interact with specific DNA regulatory sequences to
      control gene expression throughout myriad cellular processes. However, the DNA
      binding specificities of only a small fraction of TFs are sufficiently
      characterized to predict the sequences that they can and cannot bind. We present
      a maximally compact, synthetic DNA sequence design for protein binding microarray
      (PBM) experiments that represents all possible DNA sequence variants of a given
      length k (that is, all 'k-mers') on a single, universal microarray. We
      constructed such all k-mer microarrays covering all 10-base pair (bp) binding
      sites by converting high-density single-stranded oligonucleotide arrays to double
      stranded (ds) DNA arrays. Using these microarrays we comprehensively determined
      the binding specificities over a full range of affinities for five TFs of
      different structural classes from yeast, worm, mouse and human. The unbiased
      coverage of all k-mers permits high-throughput interrogation of binding site
      preferences, including nucleotide interdependencies, at unprecedented resolution.

PMID- 16998474
TI  - Neddylation of a breast cancer-associated protein recruits a class III histone
      deacetylase that represses NFkappaB-dependent transcription.
AB  - Neddylation has an important role in ubiquitin-mediated protein degradation
      through modification of cullins, which are the main substrates for NEDD8
      modification. Here, we show that breast cancer-associated protein 3 (BCA3) is a
      NEDD8 substrate. BCA3 suppressed NFkappaB-dependent transcription through its
      ability to bind to p65 and the cyclin D1 promoter in a neddylation-dependent
      manner. Transcriptional suppression mediated by BCA3 may be attributed to the
      ability of neddylated BCA3 to recruit SIRT1, a class III histone deacetylase.
      Silencing of endogenous BCA3 in DU145 and MCF7 cells enhanced NFkappaB
      transcription and inhibited tumour necrosis factor (TNF)alpha-induced apoptosis.
      Conversely, BCA3 silencing could be reversed by over-expression of wild-type BCA3
      and SENP8, a NEDD8-specific protease, but not by neddylation-deficient BCA3 or a
      SENP8 mutant. These results provide a crucial link between neddylation and
      transcriptional regulation by SIRT1, a NAD-dependent histone deacetylase that
      prolongs life span in yeast and worms.

PMID- 16998475
TI  - Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis.
AB  - Autophagy-related gene (Atg) 5 is a gene product required for the formation of
      autophagosomes. Here, we report that Atg5, in addition to the promotion of
      autophagy, enhances susceptibility towards apoptotic stimuli. Enforced expression
      of Atg5-sensitized tumour cells to anticancer drug treatment both in vitro and in
      vivo. In contrast, silencing the Atg5 gene with short interfering RNA (siRNA)
      resulted in partial resistance to chemotherapy. Apoptosis was associated with
      calpain-mediated Atg5 cleavage, resulting in an amino-terminal cleavage product
      with a relative molecular mass of 24,000 (Mr 24K). Atg5 cleavage was observed
      independent of the cell type and the apoptotic stimulus, suggesting that calpain
      activation and Atg5 cleavage are general phenomena in apoptotic cells. Truncated
      Atg5 translocated from the cytosol to mitochondria, associated with the anti
      apoptotic molecule Bcl-xL and triggered cytochrome c release and caspase
      activation. Taken together, calpain-mediated Atg5 cleavage provokes apoptotic
      cell death, therefore, represents a molecular link between autophagy and
      apoptosis--a finding with potential importance for clinical anticancer therapies.

PMID- 16998476
TI  - Self-organization of microtubule bundles in anucleate fission yeast cells.
AB  - Self-organization of cellular structures is an emerging principle underlying
      cellular architecture. Properties of dynamic microtubules and microtubule-binding
      proteins contribute to the self-assembly of structures such as microtubule
      asters. In the fission yeast Schizosaccharomyces pombe, longitudinal arrays of
      cytoplasmic microtubule bundles regulate cell polarity and nuclear positioning.
      These bundles are thought to be organized from the nucleus at multiple interphase
      microtubule organizing centres (iMTOCs). Here, we find that microtubule bundles
      assemble even in cells that lack a nucleus. These bundles have normal
      organization, dynamics and orientation, and exhibit anti-parallel overlaps in the
      middle of the cell. The mechanisms that are responsible for formation of these
      microtubule bundles include cytoplasmic microtubule nucleation, microtubule
      release from the equatorial MTOC (eMTOC), and the dynamic fusion and splitting of
      microtubule bundles. Bundle formation and organization are dependent on mto1p
      (gamma-TUC associated protein), ase1p (PRC1), klp2p (kinesin-14) and tip1p (CLIP
      170). Positioning of nuclear fragments and polarity factors by these microtubules
      illustrates how self-organization of these bundles contributes to establishing
      global spatial order.

PMID- 16998477
TI  - Self-organization of interphase microtubule arrays in fission yeast.
AB  - Microtubule organization is key to eukaryotic cell structure and function. In
      most animal cells, interphase microtubules organize around the centrosome, the
      major microtubule organizing centre (MTOC). Interphase microtubules can also
      become organized independently of a centrosome, but how acentrosomal microtubules
      arrays form and whether they are functionally equivalent to centrosomal arrays
      remains poorly understood. Here, we show that the interphase microtubule arrays
      of fission yeast cells can persist independently of nuclear-associated MTOCs,
      including the spindle pole body (SPB)--the centrosomal equivalent. By
      artificially enucleating cells, we show that arrays can form de novo (self
      organize) without nuclear-associated MTOCs, but require the microtubule nucleator
      mod20-mbo1-mto1 (refs 3-5), the bundling factor ase1 (refs 6,7), and the kinesin
      klp2 (refs 8,9). Microtubule arrays in enucleated and nucleated cells are
      morphologically indistinguishable and similarly locate to the cellular axis and
      centre. By simultaneously tracking nuclear-independent and SPB-associated
      microtubule arrays within individual nucleated cells, we show that both define
      the cell centre with comparable precision. We propose that in fission yeast,
      nuclear-independent, self-organized, acentrosomal microtubule arrays are
      structurally and functionally equivalent to centrosomal arrays.

PMID- 16998478
TI  - Oocyte signals derived from polyunsaturated fatty acids control sperm recruitment
      in vivo.
AB  - A fundamental question in animal development is how motile cells find their
      correct target destinations. During mating in the nematode Caenorhabditis
      elegans, males inject sperm through the hermaphrodite vulva into the uterus.
      Amoeboid sperm crawl around fertilized eggs to the spermatheca--a convoluted tube
      where fertilization occurs. Here, we show that polyunsaturated fatty acids
      (PUFAs), the precursors of eicosanoid signalling molecules, function in oocytes
      to control directional sperm motility within the uterus. PUFAs are transported
      from the intestine, the site of fat metabolism, to the oocytes yolk, which is a
      lipoprotein complex. Loss of the RME-2 low-density lipoprotein (LDL) receptor,
      which mediates yolk endocytosis and fatty acid transport into oocytes, causes
      severe defects in sperm targeting. We used an RNAi screen to identify lipid
      regulators required for directional sperm motility. Our results support the
      hypothesis that PUFAs function in oocytes as precursors of signals that control
      sperm recruitment to the spermatheca. A common property of PUFAs in mammals and
      C. elegans is that these fats control local recruitment of motile cells to their
      target tissues.

PMID- 16998479
TI  - Condensin and Repo-Man-PP1 co-operate in the regulation of chromosome
      architecture during mitosis.
AB  - The reversible condensation of chromosomes during cell division remains a classic
      problem in cell biology. Condensation requires the condensin complex in certain
      experimental systems, but not in many others. Anaphase chromosome segregation
      almost always fails in condensin-depleted cells, leading to the formation of
      prominent chromatin bridges and cytokinesis failure. Here, live-cell analysis of
      chicken DT40 cells bearing a conditional knockout of condensin subunit SMC2
      revealed that condensin-depleted chromosomes abruptly lose their compact
      architecture during anaphase and form massive chromatin bridges. The compact
      chromosome structure can be preserved and anaphase chromosome segregation rescued
      by preventing the targeting subunit Repo-Man from recruiting protein phosphatase
      1 (PP1) to chromatin at anaphase onset. This study identifies an activity
      critical for mitotic chromosome structure that is inactivated by Repo-Man-PP1
      during anaphase. This activity, provisionally termed 'regulator of chromosome
      architecture' (RCA), cooperates with condensin to preserve the characteristic
      chromosome architecture during mitosis.

PMID- 16998480
TI  - Nitric oxide activates TRP channels by cysteine S-nitrosylation.
AB  - Transient receptor potential (TRP) proteins form plasma-membrane cation channels
      that act as sensors for diverse cellular stimuli. Here, we report a novel
      activation mechanism mediated by cysteine S-nitrosylation in TRP channels.
      Recombinant TRPC1, TRPC4, TRPC5, TRPV1, TRPV3 and TRPV4 of the TRPC and TRPV
      families, which are commonly classified as receptor-activated channels and
      thermosensor channels, induce entry of Ca(2+) into cells in response to nitric
      oxide (NO). Labeling and functional assays using cysteine mutants, together with
      membrane sidedness in activating reactive disulfides, show that cytoplasmically
      accessible Cys553 and nearby Cys558 are nitrosylation sites mediating NO
      sensitivity in TRPC5. The responsive TRP proteins have conserved cysteines on the
      same N-terminal side of the pore region. Notably, nitrosylation of native TRPC5
      upon G protein-coupled ATP receptor stimulation elicits entry of Ca(2+) into
      endothelial cells. These findings reveal the structural motif for the NO
      sensitive activation gate in TRP channels and indicate that NO sensors are a new
      functional category of cellular receptors extending over different TRP families.

PMID- 16998481
TI  - NMDA receptors are critical for unleashing consolidated auditory fear memories.
AB  - Memories are dynamic and can change when recalled. The process that returns
      memories to a labile state during remembering is unclear. We found that the
      presence of NMDA, but not AMPA, receptor antagonists in the amygdala prior to
      recall prevented the consolidated fear memory from returning to a labile state.
      These findings suggest that NMDA receptors in the amygdala are critical for
      transforming a memory from a fixed to a labile state.

PMID- 16998482
TI  - A human parietal face area contains aligned head-centered visual and tactile
      maps.
AB  - Visually guided eating, biting and kissing, and avoiding objects moving toward
      the face and toward which the face moves require prompt, coordinated processing
      of spatial visual and somatosensory information in order to protect the face and
      the brain. Single-cell recordings in parietal cortex have identified multisensory
      neurons with spatially restricted, aligned visual and somatosensory receptive
      fields, but so far, there has been no evidence for a topographic map in this
      area. Here we mapped the organization of a multisensory parietal face area in
      humans by acquiring functional magnetic resonance images while varying the polar
      angle of facial air puffs and close-up visual stimuli. We found aligned maps of
      tactile and near-face visual stimuli at the highest level of human association
      cortex-namely, in the superior part of the postcentral sulcus. We show that this
      area may code the location of visual stimuli with respect to the face, not with
      respect to the retina.

PMID- 16998483
TI  - Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic
      stem cells.
AB  - In individuals with chronic myeloid leukemia (CML) treated by autologous
      hematopoietic stem cell (HSC) transplantation, malignant progenitors in the graft
      contribute to leukemic relapse, but the mechanisms of homing and engraftment of
      leukemic CML stem cells are unknown. Here we show that CD44 expression is
      increased on mouse stem-progenitor cells expressing BCR-ABL and that CD44
      contributes functional E-selectin ligands. In a mouse retroviral transplantation
      model of CML, BCR-ABL1-transduced progenitors from CD44-mutant donors are
      defective in homing to recipient marrow, resulting in decreased engraftment and
      impaired induction of CML-like myeloproliferative disease. By contrast, CD44
      deficient stem cells transduced with empty retrovirus engraft as efficiently as
      do wild-type HSCs. CD44 is dispensable for induction of acute B-lymphoblastic
      leukemia by BCR-ABL, indicating that CD44 is specifically required on leukemic
      cells that initiate CML. The requirement for donor CD44 is bypassed by direct
      intrafemoral injection of BCR-ABL1-transduced CD44-deficient stem cells or by
      coexpression of human CD44. Antibody to CD44 attenuates induction of CML-like
      leukemia in recipients. These results show that BCR-ABL-expressing leukemic stem
      cells depend to a greater extent on CD44 for homing and engraftment than do
      normal HSCs, and argue that CD44 blockade may be beneficial in autologous
      transplantation in CML.

PMID- 16998484
TI  - Targeting of CD44 eradicates human acute myeloid leukemic stem cells.
AB  - The long-term survival of patients with acute myeloid leukemia (AML) is dismally
      poor. A permanent cure of AML requires elimination of leukemic stem cells (LSCs),
      the only cell type capable of initiating and maintaining the leukemic clonal
      hierarchy. We report a therapeutic approach using an activating monoclonal
      antibody directed to the adhesion molecule CD44. In vivo administration of this
      antibody to nonobese diabetic-severe combined immune-deficient mice transplanted
      with human AML markedly reduced leukemic repopulation. Absence of leukemia in
      serially transplanted mice demonstrated that AML LSCs are directly targeted.
      Mechanisms underlying this eradication included interference with transport to
      stem cell-supportive microenvironmental niches and alteration of AML-LSC fate,
      identifying CD44 as a key regulator of AML LSCs. The finding that AML LSCs
      require interaction with a niche to maintain their stem cell properties provides
      a therapeutic strategy to eliminate quiescent AML LSCs and may be applicable to
      other types of cancer stem cells.

PMID- 16998485
TI  - Monoculture-derived T lymphocytes specific for multiple viruses expand and
      produce clinically relevant effects in immunocompromised individuals.
AB  - Immunocompromised individuals are at high risk for life-threatening diseases,
      especially those caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV) and
      adenovirus. Conventional therapeutics are primarily active only against CMV, and
      resistance is frequent. Adoptive transfer of polyclonal cytotoxic T lymphocytes
      (CTLs) specific for CMV or EBV seems promising, but it is unclear whether this
      strategy can be extended to adenovirus, which comprises many serotypes. In
      addition, the preparation of a specific CTL line for each virus in every eligible
      individual would be impractical. Here we describe genetic modification of antigen
      presenting cell lines to facilitate the production of CD4(+) and CD8(+) T
      lymphocytes specific for CMV, EBV and several serotypes of adenovirus from a
      single cell culture. When administered to immunocompromised individuals, the
      single T lymphocyte line expands into multiple discrete virus-specific
      populations that supply clinically measurable antiviral activity. Monoculture
      derived multispecific CTL infusion could provide a safe and efficient means to
      restore virus-specific immunity in the immunocompromised host.

PMID- 16998487
TI  - An exonic splicing silencer represses spliceosome assembly after ATP-dependent
      exon recognition.
AB  - Precursor messenger RNA splicing is catalyzed by the spliceosome, a
      macromolecular complex that assembles in a stepwise process. The spliceosome's
      dynamic nature suggests the potential for regulation at numerous points along the
      assembly pathway; however, thus far, naturally occurring regulation of splicing
      has only been found to influence a small subset of spliceosomal intermediates.
      Here we report that the exonic splicing silencer (ESS1) that represses splicing
      of PTPRC (encoding CD45) exon 4 does not function by the typical mechanism of
      inhibiting binding of U1 or U2 small nuclear ribonucleoproteins (snRNPs) to the
      splice sites. Instead, a U1-, U2- and ATP-dependent complex forms across exon 4
      that is required for inhibiting progression to the U4-U6-U5 tri-snRNP-containing
      B complex. Such inhibition represents a new mechanism for splicing regulation and
      suggests that regulation can probably occur at many of the transitions along the
      spliceosome assembly pathway.

PMID- 16998486
TI  - Structural analysis of kasugamycin inhibition of translation.
AB  - The prokaryotic ribosome is an important target of antibiotic action. We
      determined the X-ray structure of the aminoglycoside kasugamycin (Ksg) in complex
      with the Escherichia coli 70S ribosome at 3.5-A resolution. The structure reveals
      that the drug binds within the messenger RNA channel of the 30S subunit between
      the universally conserved G926 and A794 nucleotides in 16S ribosomal RNA, which
      are sites of Ksg resistance. To our surprise, Ksg resistance mutations do not
      inhibit binding of the drug to the ribosome. The present structural and
      biochemical results indicate that inhibition by Ksg and Ksg resistance are
      closely linked to the structure of the mRNA at the junction of the peptidyl-tRNA
      and exit-tRNA sites (P and E sites).

PMID- 16998488
TI  - The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding
      and inhibit canonical translation initiation.
AB  - Kasugamycin (Ksg) specifically inhibits translation initiation of canonical but
      not of leaderless messenger RNAs. Ksg inhibition is thought to occur by direct
      competition with initiator transfer RNA. The 3.35-A structure of Ksg bound to the
      30S ribosomal subunit presented here provides a structural description of two Ksg
      binding sites as well as a basis for understanding Ksg resistance. Notably,
      neither binding position overlaps with P-site tRNA; instead, Ksg mimics codon
      nucleotides at the P and E sites by binding within the path of the mRNA. Coupled
      with biochemical experiments, our results suggest that Ksg indirectly inhibits P
      site tRNA binding through perturbation of the mRNA-tRNA codon-anticodon
      interaction during 30S canonical initiation. In contrast, for 70S-type initiation
      on leaderless mRNA, the overlap between mRNA and Ksg is reduced and the binding
      of tRNA is further stabilized by the presence of the 50S subunit, minimizing Ksg
      efficacy.

PMID- 16998489
TI  - A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with
      lower risk of age-related macular degeneration.
AB  - Age-related macular degeneration (AMD; OMIM #603075) is the most frequent cause
      of visual impairment in the elderly population, with severe disease affecting
      nearly 10% of individuals of European descent over the age of 75 years. It is a
      complex disease in which genetic and environmental factors contribute to
      susceptibility. Complement factor H (CFH) has recently been identified as a major
      AMD susceptibility gene, and the Y402H polymorphism has been proposed as the
      likely causative factor. We genotyped polymorphisms spanning the cluster of CFH
      and five CFH-related genes on chromosome 1q23 in 173 individuals with severe
      neovascular AMD and 170 elderly controls with no signs of AMD. Detailed analysis
      showed a common haplotype associated with decreased risk of AMD that was present
      on 20% of chromosomes of controls and 8% of chromosomes of individuals with AMD.
      We found that this haplotype carried a deletion of CFHR1 and CFHR3, and the
      proteins encoded by these genes were absent in serum of homozygotes. The
      protective effect of the deletion haplotype cannot be attributed to linkage
      disequilibrium with Y402H and was replicated in an independent sample.

PMID- 16998490
TI  - Mammalian ultraconserved elements are strongly depleted among segmental
      duplications and copy number variants.
AB  - An earlier search in the human, mouse and rat genomes for sequences that are 100%
      conserved in orthologous segments and > or = 200 bp in length identified 481
      distinct sequences. These human-mouse-rat sequences, which represent
      ultraconserved elements (UCEs), are believed to be important for functions
      involving DNA binding, RNA processing and the regulation of transcription and
      development. In vivo and additional computational studies of UCEs and other
      highly conserved sequences are consistent with these functional associations,
      with some observations indicating enhancer-like activity for these elements.
      Here, we show that UCEs are significantly depleted among segmental duplications
      and copy number variants. Notably, of the UCEs that are found in segmental
      duplications or copy number variants, the majority overlap exons, indicating,
      along with other findings presented, that UCEs overlapping exons represent a
      distinct subset.

PMID- 16998492
TI  - Signals mediated by transforming growth factor-beta initiate autoimmune
      encephalomyelitis, but chronic inflammation is needed to sustain disease.
AB  - It is unclear whether TGF-beta, a critical differentiation factor for T cells
      producing interleukin 17 (T(H)-17 cells), is required for the initiation of
      experimental autoimmune encephalomyelitis (EAE) in vivo. Here we show that mice
      whose T cells cannot respond to TGF-beta signaling lack T(H)-17 cells and do not
      develop EAE despite the presence of T helper cell type 1 infiltrates in the
      spinal cord. Local but not systemic antibody blockade of TGF-beta prevented T(H)
      17 cell differentiation and the onset of EAE. The pathogen stimulus zymosan, like
      mycobacterium, induced T(H)-17 cells and initiated EAE, but the disease was
      transient and correlated with reduced production of interleukin 23. These data
      show that TGF-beta is essential for the initiation of EAE and suggest that
      disease progression may require ongoing chronic inflammation and production of
      interleukin 23.

PMID- 16998491
TI  - A high-resolution HLA and SNP haplotype map for disease association studies in
      the extended human MHC.
AB  - The proteins encoded by the classical HLA class I and class II genes in the major
      histocompatibility complex (MHC) are highly polymorphic and are essential in self
      versus non-self immune recognition. HLA variation is a crucial determinant of
      transplant rejection and susceptibility to a large number of infectious and
      autoimmune diseases. Yet identification of causal variants is problematic owing
      to linkage disequilibrium that extends across multiple HLA and non-HLA genes in
      the MHC. We therefore set out to characterize the linkage disequilibrium patterns
      between the highly polymorphic HLA genes and background variation by typing the
      classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms
      across four population samples. The analysis provides informative tag SNPs that
      capture much of the common variation in the MHC region and that could be used in
      disease association studies, and it provides new insight into the evolutionary
      dynamics and ancestral origins of the HLA loci and their haplotypes.

PMID- 16998493
TI  - Regulation of effector T cells by antigen-presenting cells via interaction of the
      C-type lectin MGL with CD45.
AB  - Homeostatic control of T cells involves tight regulation of effector T cells to
      prevent excessive activation that can cause tissue damage and autoimmunity.
      Little is known, however, about whether antigen-presenting cells (APCs) are also
      involved in maintaining immune system homeostasis once effector T cells are
      stimulated. Here we found that immature APCs downregulated effector T cell
      function by a mechanism involving the C-type lectin MGL expressed by APCs.
      Glycosylation-dependent interactions of MGL with CD45 on effector T cells
      negatively regulated T cell receptor-mediated signaling and T cell-dependent
      cytokine responses, which in turn decreased T cell proliferation and increased T
      cell death. Thus, regulation of effector T cells by MGL expressed on APCs may
      provide a target for regulating chronic inflammatory and autoimmune diseases.

PMID- 16998496
TI  - Clinical management of BRCA1 and BRCA2 mutation carriers.
AB  - The cancer susceptibility genes BRCA1 and BRCA2 appear to be responsible for
      virtually all hereditary breast ovarian families, and a smaller subset of
      hereditary site-specific breast cancer families. Fortunately, effective
      strategies have been developed to reduce the risk for the development of breast
      and ovarian cancer in women with BRCA1/2 mutations, making genetic testing for
      these mutations an important part of the management at women with a strong family
      history of these diseases. Here, we review the current evidence for risk
      reduction strategies and outline future research directions.

PMID- 16998497
TI  - Modifiers of risk of hereditary breast cancer.
AB  - Mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of breast and
      ovarian cancer. The risk varies from individual to individual, and it appears
      that the risk has increased in recent generations. These observations imply that
      non-genetic factors may modify the inherited risk. To date, the factors that
      appear most strongly to modify the risk include reproductive histories and
      exogenous hormones. Oral contraceptives are associated with a profound reduction
      in the risk of ovarian cancer, and with little or no increase in the risk of
      breast cancer. Other modifying factors include age of menarche, parity,
      breastfeeding and oophorectomy. The effect of parity is different in BRCA1 and
      BRCA2 carriers. Multiparity appears to be protective in BRCA1 carriers, but is
      associated with an increase in risk in BRCA2 carriers. Oophorectomy has been
      associated with reductions in both the risk of breast and ovarian cancer.
      Knowledge of these risk factors will be useful for managing risk and for
      developing prevention strategies.

PMID- 16998498
TI  - Pathology and gene expression of hereditary breast tumors associated with BRCA1,
      BRCA2 and CHEK2 gene mutations.
AB  - Tumors arising in BRCA1 and BRCA2 mutation carriers appear to have specific
      pathological and gene expression profiles, which show a high level of
      concordance. BRCA1 tumors are high-grade, negative for hormone receptors, have a
      high proliferation rate, and are positive for some cell cycle promoter genes.
      BRCA2 tumors present a phenotype opposite to BRCA1 tumors but very similar to
      sporadic tumors, except that BRCA2 overexpress some DNA repair markers such as
      CHEK2, show high cytoplasmic expression of RAD51, and are negative for HER-2
      amplification and expression. Some of these characteristics have also been found
      in cDNA expression studies, although more analysis are necessary in order to
      obtain new markers that can be associated with a germ line mutation in BRCA1 or
      BRCA2. In this way, some studies in normal tissues of BRCA1/2 carriers suggest
      that differences exist in the level of expression of some genes when compared
      with noncarriers. Finally, IHC studies in tumors carrying a mutation in CHEK2 are
      rare and show contradictory results, probably due to the low number of these
      cases. However, they represent an example showing how different mutations of the
      same gene may be associated with specific histological subtypes of cancer.

PMID- 16998499
TI  - Basal-like breast cancer and the BRCA1 phenotype.
AB  - Breast cancers arising in germline carriers of BRCA1 mutations have a
      characteristic phenotype that has been shown in many studies to differentiate
      BRCA1 tumours from sporadic tumours. Recently, it has become clear that the
      characteristic phenotype of BRCA1 tumours is due to expression of the basal-like
      phenotype. We review these phenotypes, the evidence for BRCA1 pathway dysfunction
      in sporadic basal-like cancers, and discuss the clinical significance of the
      basal-like phenotype for cancer genetics and treatment.

PMID- 16998500
TI  - The role of BRCA1 in transcriptional regulation and cell cycle control.
AB  - The exact functions of BRCA1 have not been fully described but it now seems
      apparent that it has roles in DNA damage repair, transcriptional regulation, cell
      cycle control and most recently in ubiquitylation. These functions of BRCA1 are
      most likely interdependent but this review will focus on the role of BRCA1 in
      relation to transcriptional regulation and in particular how this impacts upon
      cell cycle control. We will (i) describe the structure of BRCA1 and how it may
      contribute to its transcription function; (ii) describe the interaction of BRCA1
      with the core transcriptional machinery (RNA polII); (iii) describe how BRCA1 may
      regulate transcription at an epigenetic level through chromatin modification;
      (iv) discuss the role of BRCA1 in modulating transcription through its
      association with sequence-specific transcription factors. Finally, we will
      discuss the possible effects of BRCA1 transcriptional regulation on downstream
      targets with known roles in cell cycle control.

PMID- 16998501
TI  - The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of
      genomic stability.
AB  - The BRCA1 and BRCA2 proteins are important in maintaining genomic stability by
      promoting efficient and precise repair of double-strand breaks. The main role of
      BRCA2 appears to involve regulating the function of RAD51 in the repair by
      homologous recombination. BRCA1 has a broader role upstream of BRCA2,
      participating in various cellular processes in response to DNA damage. The DNA
      repair defect associated with mutations in BRCA1 or BRCA2 could be exploited to
      develop new targeted therapeutic approaches for cancer occurring in mutation
      carriers.

PMID- 16998502
TI  - Fanconi anaemia genes and susceptibility to cancer.
AB  - Fanconi anaemia (FA) is a rare recessive disorder associated with chromosomal
      fragility, aplastic anaemia, congenital abnormalities and a high risk of cancer,
      including acute myeloid leukaemia and squamous cell carcinomas. The
      identification of 11 different FA genes has revealed a complex web of interacting
      proteins that are involved in the recognition or repair of DNA interstrand
      crosslinks and perhaps other forms of DNA damage. Bi-allelic mutations in BRCA2
      are associated with a rare and highly cancer-prone form of FA, and the DNA
      helicase BRIP1 (formerly BACH1) is mutated in FA group J. There is little
      convincing evidence that FA heterozygotes are at increased risk of cancer, but
      larger studies are needed to address the possibility of modest risk effects.
      Somatic inactivation of the FA pathway by mutation or epigenetic silencing has
      been observed in several different types of sporadic cancer, and this may have
      important implications for targeted chemotherapy. Inhibition of this pathway
      represents a possible route to sensitization of tumours to DNA crosslinking drugs
      such as cisplatin.

PMID- 16998503
TI  - Mouse models of BRCA1 and BRCA2 deficiency: past lessons, current understanding
      and future prospects.
AB  - Germline mutations in BRCA1 and BRCA2 are responsible for a large proportion of
      hereditary breast and ovarian cancers. Soon after the identification of both
      genes in the mid-1990s, investigators set out to develop mouse models for the
      associated disease. Whereas conventional Brca1 and Brca2 mouse mutants did not
      reveal a strong phenotype in a heterozygous setting, most homozygous mutations
      caused embryonic lethality. Consequently, development of mouse models for BRCA
      associated tumorigenesis required the generation of tissue-specific conditional
      knockout animals. In this review, we give an overview of the conventional and the
      conditional mouse models of BRCA1 and BRCA2 deficiency generated over the last
      decade, as well as the contribution of these models to our understanding of the
      biological and molecular functions of BRCA1 and BRCA2. The most advanced mouse
      models for BRCA1- and BRCA2-associated tumorigenesis mimic human disease to the
      extent that they can be used in studies addressing clinically relevant questions.
      These models will help to resolve yet unanswered questions and to translate our
      increasing knowledge of BRCA1 and BRCA2 biology into clinical practice.

PMID- 16998504
TI  - Models of genetic susceptibility to breast cancer.
AB  - One of the most important risk factors for breast cancer is family history of the
      disease, indicating that genetic factors are important determinants of breast
      cancer risk. A number of breast cancer susceptibility genes have been identified,
      the most important being BRCA1 and BRCA2. However, it is estimated that all the
      currently known breast cancer susceptibility genes accounts for less than 25% of
      the familial aggregation of breast cancer. In this paper, we review the evidence
      for other breast cancer susceptibility genes arising from twin studies, pedigree
      analysis and studies of phenotypes associated with breast cancer, and the
      progress towards finding other breast cancer susceptibility genes through linkage
      and association studies. Taken together, the available evidence indicates that
      susceptibility to breast cancer is mediated through variants in many genes, each
      conferring a moderate risk of the disease. Such a model of susceptibility has
      implications for both risk prediction and for future gene identification studies.

PMID- 16998505
TI  - ATM and breast cancer susceptibility.
AB  - ATM was originally identified by positional cloning as the gene that underlies
      the autosomal recessive condition ataxia-telangiectasia. The encoded protein
      plays a central role in the complex processes that repair DNA double-strand
      breaks. Nearly 20 years ago, epidemiological surveys of relatives of ataxia
      telangiectasia cases suggested that female relatives were at modestly increased
      risk of breast cancer. Subsequently, many studies have tried to clarify the role
      of ATM in breast cancer susceptibility, but have produced inconclusive and/or
      inconsistent results. Recently, large epidemiological and molecular studies have
      finally provided conclusive evidence that ATM mutations that cause ataxia
      telangiectasia are breast cancer susceptibility alleles.

PMID- 16998506
TI  - The CHEK2 gene and inherited breast cancer susceptibility.
AB  - Checkpoint kinase 2 (CHEK2, Chk2) emerges as an important signal transducer of
      cellular responses to DNA damage and a candidate tumor suppressor whose defects
      contribute to molecular pathogenesis of diverse types of human malignancies, both
      sporadic and hereditary. Here, we briefly outline the molecular properties,
      regulation and physiological role of CHEK2, and review in more detail its defects
      that predispose to tumors, with particular emphasis on familial breast cancer.
      The frequency, penetrance and epidemiological as well as clinical significance of
      the two most studied breast cancer-predisposing variants of the CHEK2 gene,
      1100delC and I157T, are highlighted in more depth, and additional CHEK2 mutations
      and their cancer relevance are discussed as well. These recent findings are
      considered also from a broader perspective of CHEK2 as the integral component of
      the ataxia telangiectasia-mutated-CHEK2-p53 pathway within the genome integrity
      maintenance system and a barrier against tumor progression. Finally, the
      potential value of information about the CHEK2 status in family counseling and
      optimizition of individualized cancer treatment is discussed.

PMID- 16998507
TI  - Receptor editing in lymphocyte development and central tolerance.
AB  - The specificities of lymphocytes for antigen are generated by a quasi-random
      process of gene rearrangement that often results in non-functional or
      autoreactive antigen receptors. Regulation of lymphocyte specificities involves
      not only the elimination of cells that display 'unsuitable' receptors for antigen
      but also the active genetic correction of these receptors by secondary
      recombination of the DNA. As I discuss here, an important mechanism for the
      genetic correction of antigen receptors is ongoing recombination, which leads to
      receptor editing. Receptor editing is probably an adaptation that is necessitated
      by the high probability of receptor autoreactivity. In both B cells and T cells,
      the genes that encode the two chains of the antigen receptor seem to be
      specialized to promote, on the one hand, the generation of diverse specificities
      and, on the other hand, the regulation of these specificities through efficient
      editing.

PMID- 16998508
TI  - Reciprocal regulation between natural killer cells and autoreactive T cells.
AB  - The initiation and the progression of autoimmune diseases stem from complex
      interactions that involve cells of both the innate and the adaptive immune
      system. As we discuss here, natural killer (NK) cells, which are components of
      the innate immune system, can inhibit or promote the activation of autoreactive T
      cells during the initiation of autoimmunity. After they have been activated,
      autoreactive T cells contribute to the homeostatic contraction of NK-cell
      populations. The dynamic interaction between NK cells and autoreactive T cells
      might indicate the transition from the innate immune triggering of autoimmunity
      to the progressive phase of the disease. Understanding the mechanisms and signals
      that control the reciprocal regulation of NK cells and autoreactive T cells could
      have important implications for treatment in the clinic.

PMID- 16998509
TI  - Immunological mechanisms of allergen-specific immunotherapy.
AB  - Allergen-specific immunotherapy has been carried out for almost a century and
      remains one of the few antigen-specific treatments for inflammatory diseases. The
      mechanisms by which allergen-specific immunotherapy exerts its effects include
      the modulation of both T-cell and B-cell responses to allergen. There is a strong
      rationale for improving the efficacy of allergen-specific immunotherapy by
      reducing the incidence and severity of adverse reactions mediated by IgE.
      Approaches to address this problem include the use of modified allergens, novel
      adjuvants and alternative routes of administration. This article reviews the
      development of allergen-specific immunotherapy, our current understanding of its
      mechanisms of action and its future prospects.

PMID- 16998510
TI  - Adipocytokines: mediators linking adipose tissue, inflammation and immunity.
AB  - There has been much effort recently to define the role of adipocytokines, which
      are soluble mediators derived mainly from adipocytes (fat cells), in the
      interaction between adipose tissue, inflammation and immunity. The adipocytokines
      adiponectin and leptin have emerged as the most abundant adipocyte products,
      thereby redefining adipose tissue as a key component not only of the endocrine
      system, but also of the immune system. Indeed, as we discuss here, several
      adipocytokines have a central role in the regulation of insulin resistance, as
      well as many aspects of inflammation and immunity. Other adipocytokines, such as
      visfatin, have only recently been identified. Understanding this rapidly growing
      family of mainly adipocyte-derived mediators might be of importance in the
      development of new therapies for obesity-associated diseases.

PMID- 16998511
TI  - B-cell memory: are subsets necessary?
AB  - B-cell memory is provided by populations of quiescent memory B cells and long
      lived plasma cells. Whereas it is clear that both of these cell populations arise
      from germinal centres, the signals and circumstances that trigger germinal-centre
      B cells to enter and then persist in memory compartments are poorly defined.
      Here, I propose that germinal centres produce memory B cells and plasma cells
      throughout the immune response and that memory B cells arise by the emigration of
      B cells that are chosen at random from the pool available in the germinal centre.
      The ability of such emigrants to survive as memory B cells depends on their
      germinal-centre 'history', with the persistence of high-affinity B-cell variants
      being favoured.

PMID- 16998512
TI  - [Transplantation in Navarra and Spain].
AB  - The donation of organs and tissues is accepted in our society as a normal
      process; thus it frequently happens that when, in the face of imminent death, we
      inform the family of the severity of the patient in an intensive care unit, they
      offer us the organs and/or tissues before they are even asked. That is to say
      that in our milieu the degree of awareness and generosity is very high. As a sort
      of magic figure, three historic events occurred at the end of 2005: on the one
      hand, Spain exceeded the figure of 35 donations per million - a world record; on
      the other hand, we obtained the lowest figure of family refusals in history, that
      is, we are now below 16 per million, which is also a magic figure that is unique
      in the world; and, besides, we exceeded the figure of 1,500 donations in one
      year. The experience of 30 years of donations and transplantations has enabled us
      to optimise methods and protocols and to efficiently distribute functions on the
      basis of specialisation. The Hospital of Navarra preferentially takes charge of
      the extraction of organs; the Virgen del Camino Hospital collects tissues; and
      the University Clinic of Navarra carries out the surgical process of the
      transplantation. In this article we present data on the different transplants,
      making continuous reference to the figures produced between the years 1995 and
      2005; we refer to previous figures and we make a comparison with the rest of
      Spain and the world.

PMID- 16998513
TI  - [Legal aspects of transplant and donation].
AB  - The Spanish model of organ and tissue donation enjoys great prestige in the world
      medical sphere and has been the object of study and imitation in different
      countries. Part of this success is due to the fact that since the year 1979
      different legal norms have been enacted that have regulated and facilitated
      donation. The current legislation on the donation and transplant of organs and
      tissues is based on the principles of the gratuity and confidentiality of the
      donation, indicating the need for facilitating the formation of organisations at
      the level of the autonomous communities and at the national level. It also
      contains the requisites for donation of both live donors and deceased donors,
      establishing the norms for certification of death due to cardiorespiratory arrest
      and due to the irreversible cease of brain functions.

PMID- 16998514
TI  - [Coordination and donation].
AB  - The progressive incorporation of organ transplants as a therapeutic resource
      resulted in organisational adaptation and overall transplant management, leading
      to the emergence of the figure of the transplant coordinator in the mid-1980s. In
      Spain, the National Organisation of Transplants (Organizacion Nacional de
      Transplantes - ONT) was created, establishing a system - called the "Spanish
      model" - based on a network of coordinators at three levels: national, the
      autonomous community and the hospital. This organisational structure is a point
      of reference at the world level. The prevalence of the Intensive Medicine
      specialisation amongst hospital transplant coordinators is remarkable. The
      majority of organs proceed from brain-dead patients with beating hearts and this
      requires the infrastructure offered by intensive care units. The functions of the
      coordinator can be summarised in guaranteeing a synchrony of all the elements and
      teams that come together in an organisational chain that has come to be called
      the "process of donation". Schematically, the crucial points that the hospital
      coordinator develops are the following: - Detection of the potential donor. -
      Maintenance of the donor. - Diagnosis of brain death. - Family consent. -
      Preparation of the hospital logistics. - Helping the relatives. - Direct
      involvement in the Program of Guarantee of Quality. - Person of reference in any
      activity related to the transplant. It would be desirable to achieve the creation
      of transplant coordination teams, with univocal messages, professionalism and a
      permanent input of the so-called "human factor", which is so necessary and also
      so close to the transplant world.

PMID- 16998515
TI  - [Transplant coordination and logistics of intra and extra-hospital cadaver donor
      tissue. "The Pamplona Model". Sequence of tasks performed from 1992-2006].
AB  - INTRODUCTION: Tissue and organ donations are the only option for many patients.
      Cerebral death (CD) facilitates this approach. However, hospitals that do not
      provide CD donors have to adapt in order to obtain donors, referred to as tissue
      donors (TD), who have died from cardiac arrest. OBJECTIVE: Is this paper it
      descripte the model for coordination and donation of intra and extra-hospital TD
      in the Autonomous Community of Navarra. It creats a program for detection,
      donation and extractions called the Pamplona Model, from 1992-2006. MATERIAL AND
      METHODS: In 1990, a transplant team was created by an Intensive Medicine
      Physician of HVC, INML and SOS-Navarra. In 1996, VCH Transplant Coordination is
      defined as a reference centre for the Tissue Transplant Programme in the
      Autonomous Community of Navarra. RESULTS: Consensus protocols for "intra and
      extra-hospital detection" of persons having died from cardiac arrest are
      developed: - Alerts from NHS-O hospitals, SOS-Navarra; judges and INML forensic
      pathologists. - Criteria for selection, search and contacts with relatives. -
      Alert serology, extraction and transport teams. - Logistics and distribution of
      tissue. - Agreed incentives: Economic, administrative and relevant regulations.
      CONCLUSIONS: The Pamplona Model, with the Virgen Del Camino hospital has made
      important contributions and is unique in the world. Intra and extra-hospital
      coordination of cadaver donor from a referred hospital, it is a scientific and
      organizational advance to have in it counts for the creation of extraction and
      transplant tissues teams.

PMID- 16998516
TI  - [Heart transplant].
AB  - A heart transplant is at present considered the treatment of choice in cases of
      terminal cardiac insufficiency refractory to medical or surgical treatment. Due
      to factors such as the greater life expectancy of the population and the more
      efficient management of acute coronary syndromes, there is an increasing number
      of people who suffer from heart failure. It is estimated that the prevalence of
      the disease in developed countries is around 1%; of this figure, some 10% are in
      an advanced stage and are thus potential receptors of a heart transplant. The
      problem is that it is still not possible to offer this therapeutic form to all of
      the patients that require it. Consequently, it is necessary to optimise the
      results of the heart transplant through the selection of patients, selection and
      management of donors, perioperative management and control of the disease due to
      graft rejection. Since the first transplant carried out in 1967, numerous
      advances and changes have taken place, which has made it possible to increase
      survival and quality of life of those who have received a new heart. In this
      article we review the most relevant aspects of the heart transplant and the
      challenges that are currently faced.

PMID- 16998517
TI  - [Kidney transplant].
AB  - The kidney transplant is the therapy of choice for the majority of the causes of
      chronic terminal kidney insufficiency, because it improves the quality of life
      and survival in comparison with dialysis. A kidney transplant from a live donor
      is an excellent alternative for the young patient in a state of pre-dialysis
      because it offers the best results. Immunosuppressive treatment must be
      individualised, seeking immunosuppressive synergy and the best safety profile,
      and must be adapted to the different stages of the kidney transplant. In the
      follow-up to the kidney transplant, cardiovascular risk factors and tumours must
      be especially taken into account, given that the death of the patient with a
      working graft is the second cause of loss of the graft following the first year
      of the transplant. The altered function of the graft is a factor of independent
      cardiovascular mortality that will require follow-up and the control of all its
      complications to postpone the entrance in dialysis.

PMID- 16998518
TI  - [Liver transplantation].
AB  - Liver transplantation is an efficient therapeutic option for terminal hepatic
      diseases. The principal indications of liver transplantation are hepatic
      cirrhosis, hepatic tumours (mainly, hepatocellular carcinoma) and acute liver
      failure. Over the years, the absolute contraindications for a transplant have
      lessened. Surgical techniques have also undergone changes. The results of liver
      transplant have improved so that survival one year after the transplant is close
      to 90% and after five years some 80% of transplanted patients continue to live.

PMID- 16998519
TI  - [Lung transplant].
AB  - A lung transplant is usually the final therapeutic option for patients with
      respiratory insufficiency. In spite of the many advances in immunology and the
      management of complications, mortality and morbidity associated with this
      transplant are far higher than with others. Acute rejection is an almost
      universal problem in the first year, while obliterative bronchitis reduces long
      term survival. Respiratory infections also play a significant role in the
      complications associated with lung transplants due to the constant exposure of
      the graft to the outside. However, the success of this therapeutic option, which
      basically depends on a suitable selection of donor and recipient, are evident,
      above all with respect to quality of life.

PMID- 16998520
TI  - [Pancreatic transplant].
AB  - Diabetes mellitus is a health concern of the first order, given the high level of
      associated morbidity and mortality. The objective, in order to slow down the
      advance of its complications before they become irreversible, is based on correct
      metabolic control. The high rate of morbidity associated with the surgery of the
      vascularized pancreas transplant and the high index of rejection have for three
      decades formed an obstacle to this being considered a valid alternative in the
      treatment of these patients. Nowadays the pancreas transplant has come to occupy
      a key position, thanks to the new regimes of immunosuppression and to the
      perfection of surgical techniques. In this article we review the evolution of the
      pancreas transplant from its beginnings to its present state.

PMID- 16998521
TI  - [Bone transplant].
AB  - We describe the methodology of the Bone and Soft Tissue Bank, from extraction and
      storage until use. Since the year 1986, with the creation of the Bone Bank in the
      University Clinic of Navarra, more than 3,000 grafts have been used for very
      different types of surgery. Bone grafts can be classified into cortical and
      spongy; the former are principally used in surgery to save tumour patients, in
      large post-traumatic reconstructions and in replacement surgery where there are
      massive bone defects and a structural support is required. The spongy grafts are
      the most used due to their numerous indications; they are especially useful in
      filling cavities that require a significant quantity of graft when the autograft
      is insufficient, or as a complement. They are also of special help in treating
      fractures when there is bone loss and in the treatment of delays in consolidation
      and pseudoarthrosis in little vascularized and atrophic zones. They are also used
      in prosthetic surgery against the presence of cavity type defects. Allografts of
      soft tissues are specially recognised in multiple ligament injuries that require
      reconstructions. Nowadays, the most utilised are those employed in surgery of the
      anterior cruciate ligament although they can be used for filling any ligament or
      tendon defect. The principal difficulties of the cortical allografts are in the
      consolidation of the ends with the bone itself and in tumour surgery, given that
      these are patients immunodepressed by the treatment, the incidence of infection
      is increased with respect to spongy grafts and soft tissues, which is irrelevant.
      In short, the increasingly widespread use of allografts is an essential
      therapeutic weapon in orthopaedic surgery and traumatology. It must be used by
      expert hands.

PMID- 16998522
TI  - [Transplant of hemopoietic progenitors].
AB  - In the second half of the XX century, the transplant of hemopoietic progenitors
      ceased to be a desperate treatment with a high incidence of complications
      implying a high mortality, and became a curative treatment for thousands of
      patients with hematological neoplasias and other diseases. Since then
      understanding of the hemopoietic stem cells has increased, peripheral blood has
      replaced bone marrow as a source of progenitors, cord blood has been established
      as a viable source of progenitors and the realisation of unrelated transplants is
      a reality for many patients. The improvement of conditioning regimes and the
      introduction of new non-myeloablative treatments have reduced relapses. The new
      diagnostic techniques and the new anti-microbial treatments have reduced
      infectious complications and their mortality. There has been an advance in
      knowledge in determining minimal residual disease and the anti-tumour effect of
      the lymphocytes of the donor, which has made it possible to widen the
      indications. Besides, new understanding of the immunobiology of the transplant
      has, on the one hand, improved the options for controlling one of the principal
      complications, the graft-versus-host disease, and, on the other, a better use is
      made of the immunotherapeutic effect of the transplant.

PMID- 16998523
TI  - [Cardiac and vascular homograft valves transplant].
AB  - The advances in the manipulation of human tissues, the development of
      cryobiology, paediatric cardiac surgery, the impossibility of obtaining an ideal
      prosthetic cardiac valve and the surgical treatment of cardiovascular infections
      have revived interest in the use of homografts. The donors of these homografts
      can be: a) Live donors: aortic and pulmonary valve of the recipient of a heart
      transplant; b) Multiorgan donors with a diagnosis of death according to
      neurological criteria, whose heart is rejected for heart transplant; c) Cadaver
      donors with asystolia of less than 8 hours. Homograft cardiac valves are the
      substitute of choice in aortic valve endocarditis, patients with counter
      indications for anticoagulation, reconstruction of the outflow tract of the right
      ventricle, aortic valve replacement in children and young adults through the Ross
      operation, and an optional indication is the aortic valve and/or rising aorta
      replacement in patients over 60 years of age. Although there are not sufficiently
      broad series of homogratfs with arterial substitutes, with respect to the number
      of patients and time of evolution, the results suggest that this can benefit
      patients with vascular infection, immunodepressed patients or complex patients
      whose technique during the operation might require a homograft.

PMID- 16998525
TI  - [Cornea transplant].
AB  - The keratoplasty, or cornea transplant, is one of the oldest surgical techniques
      in opthalmology, whose indication are: 1) tectonic, in order to preserve corneal
      anatomy and integrity; 2) clinical, in order to eliminate the inflamed corneal
      tissue in cases refractory to medical treatment; 3) optical, in order to improve
      visual acuity; and 4) cosmetic, in order to improve the appearance of the eye.
      Improvements in technique and instruments, as well as in post-operative treatment
      and the means of preserving donated tissue, have improved survival of the grafts.
      The Pamplona Model of transplant coordination of the Virgen del Camino Hospital
      is considered to be original and unique in Spain. The logistics of this program
      include the protocol for detection and extraction of corneas as well as for
      keratoplasties.

PMID- 16998526
TI  - [The most common infections in the transplanted patient].
AB  - Organ transplantation has become one of the most important areas of medical
      research and, at present, is still the only therapeutical tool for several
      diseases. However, there are a number of factors related to transplantation, like
      immunosuppression and prolonged neutropenia that affect the incidence of
      infection. These infections are somehow peculiar to transplant recipients. In
      fact, there are infectious diseases that only occur in immunodepression
      situations and, moreover, clinical expression of these infectious diseases can be
      quite different from that in immunocompetent patients. Besides these aspects,
      some infections, due to the high prevalence described, must be considered for
      prevention strategies because they continue to be a principal cause of morbidity
      and mortality, either due to direct effects or to their implication in the
      pathogenesis of rejection. These strategies commence before transplantation by
      active immunization through vaccine administration to the patient and to people
      in the milieu and continue after transplantation with prophylaxis or pre-emptive
      therapy. The importance of infectious diseases in the evolution and prognosis of
      transplant recipients gives a special meaning to the understanding of associated
      infections, their clinical expression and ways of prevention and treatment.

PMID- 16998527
TI  - [Monitoring and secondary effects of immunosuppressants in the transplant].
AB  - The success of organ transplants and their consideration as a clearly established
      treatment in some indications is due to the development of immunosuppressant
      drugs. While it was not the first of the drugs to be employed, the introduction
      of cyclosporin in the 1980s in immunosuppressant treatment made possible an
      increase in the number of transplants and the success of this practice. From then
      onwards, immunosuppression has been based on the use of a combination of drugs,
      initially cyclosporin, corticoids and azathioprine. In recent years new drugs
      have been introduced that have opened up the possibilities of treatment. But many
      pending questions remain, due to the toxicity associated with their use and the
      possibility of interaction with other drugs, which complicates their use and can
      compromise the prognoses of these patients. Calcineurin inhibitors and mTOR are
      the drugs involved with greater frequency in interactions with other drugs, which
      makes it necessary to anticipate this possibility when the concomitant medication
      is changed.

PMID- 16998528
TI  - [Cell transplant and regenerative therapy with stem cells].
AB  - One of the fields of medicine that has raised the most expectations in recent
      years is cell therapy with stem cells. The isolation of human embryo cells, the
      apparent and unexpected potentiality of adult stem cells and the development of
      gene therapy lead us to imagine a hopeful future for a significant number of
      diseases that are at present incurable. In this article we will sketch out the
      panorama of stem cell research, describing the main achievements in this field as
      well as some of the questions that await an answer. In spite of the great
      expectations, it is essential that we maintain a critical and realistic spirit
      when it comes to analysing the scientific advances in this area.

PMID- 16998529
TI  - AMP-activated protein kinase--the fat controller of the energy railroad.
AB  - AMP-activated protein kinase plays an important role in the regulation of lipid
      metabolism in response to metabolic stress and energy demand. It is also under
      endocrine control. AMPK acts at multiple steps and has a central role controlling
      fatty acid, triglyceride, and cholesterol synthesis, as well as the oxidation of
      fatty acids through direct phosphorylation effects and the control of gene
      transcription. As such, it can be considered to be the fat controller of the
      energy railroad. It is thought that AMPK may be a major mediator of the health
      benefits of exercise in mitigating the development of obesity and age-onset
      diseases.

PMID- 16998530
TI  - PTP1B and TC-PTP: novel roles in immune-cell signaling.
AB  - It has recently been demonstrated that the protein tyrosine phosphatase (PTP)
      PTP1B and the T-cell PTP (TC-PTP) target several substrates involved in immune
      cell signaling. Recent data have furthered the view of these 2 PTP members as key
      regulators of the immune response. This review will focus on the substrate
      specificities of PTP1B and TC-PTP and their roles in immune cell signaling, and
      will discuss some new data implicating PTP1B and TC-PTP in myeloid development.

PMID- 16998531
TI  - Vanadium and bone development: putative signaling pathways.
AB  - Vanadium is a trace element present in practically all cells in plants and
      animals. It exerts interesting actions in living systems. At pharmacological
      doses, vanadium compounds display relevant biological actions such as mimicking
      insulin and growth factors as well as having osteogenic activity. Some vanadium
      compounds also show antitumoral properties. The importance of vanadium in bone
      arises from the studies developed to establish the essentiality of this element
      in animals and humans. Bone tissue, where the element seems to play an important
      role, accumulates great amounts of vanadium. This paper reviews the physiology of
      osteoblasts, the involvement of different growth factors on bone development, and
      the effects of vanadium derivatives on the skeletal system of animal models and
      bone-related cells. Two cellular lines are discussed in particular; one derived
      from a rat osteosarcoma (UMR106) and the other is a nontransformed osteoblast
      cell line (MC3T3-E1). The effects of different growth factors and their
      mechanisms of action in these cellular lines are reviewed. These models of
      osteoblasts are especially useful in understanding the intracellular signaling
      pathways of vanadium derivatives in hard tissues. Vanadium uses an intricate
      interplay of intracellular mechanisms to exert different biochemical and
      pharmacological actions. The effects of vanadium derivatives on some cellular
      signaling pathways related to insulin are compiled in this review. The
      comprehension of these intracellular signaling pathways may facilitate the design
      of vanadium compounds with promising therapeutic applications as well as the
      understanding of secondary side effects derived from the use of vanadium as a
      therapeutic agent.

PMID- 16998532
TI  - Role of the Go/i signaling network in the regulation of neurite outgrowth.
AB  - Neurite outgrowth is a complex differentiation process stimulated by many
      neuronal growth factors and transmitters and by electrical activity. Among these
      stimuli are ligands for G-protein-coupled receptors (GPCR) that function as
      neurotransmitters. The pathways involved in GPCR-triggered neurite outgrowth are
      not fully understood. Many of these receptors couple to Galphao, one of the most
      abundant proteins in the neuronal growth cones. We have studied the Go signaling
      network involved in neurite outgrowth in Neuro2A cells. Galphao can induce
      neurite outgrowth. The CB1 cannabinoid receptor, a Go/i-coupled receptor
      expressed endogenously in Neuro2A cells, triggers neurite outgrowth by activating
      Rap1, which promotes the Galphao-stimulated proteasomal degradation of Rap1GAPII.
      CB1-receptor-mediated Rap1 activation leads to the activation of a signaling
      network that includes the small guanosine triphosphate (GTP)ases Ral and Rac, the
      protein kinases Src, and c-Jun N-terminal kinase (JNK), which converge onto the
      activation of signal transducer and activator of transcription 3 (Stat3), a key
      transcription factor that mediates the gene expression process of neurite
      outgrowth in Neuro2A cells. This review describes current findings from our
      laboratory and also discusses alternative pathways that Go/i might mediate to
      trigger neurite outgrowth. We also analyze the role neurotransmitters, which
      stimulate Go/i to activate a complex signaling network controlling neurite
      outgrowth, play in regeneration after neuronal injury.

PMID- 16998533
TI  - Roles of nuclear NPY and NPY receptors in the regulation of the endocardial
      endothelium and heart function.
AB  - It is now well accepted that the heart is a multifunctional organ in which
      endothelial cells, and more particularly endocardial endothelial cells (EECs),
      seem to play an important role in regulating and maintaining cardiac excitation
      contraction coupling. Even if major differences exist between vascular
      endothelial cells (VECs) and EECs, all endothelial cells including EECs release a
      variety of auto- and paracrine factors such as nitric oxide, endothelin-1,
      angiotensin II, and neuropeptide Y. All these factors were reported to affect
      cardiomyocyte contractile performance and rhythmicity. In this review, findings
      on the morphology of EECs, differences between EECs and other types of
      endothelial cells, interactions between EECs and the adjacent cardiomyocytes, and
      effects of NPY on the heart will be presented. We will also show evidence on the
      presence and localization of NPY and the Y1 receptor in the endocardial
      endothelium and discuss their role in the regulation of cytosolic and nuclear
      free calcium.

PMID- 16998534
TI  - Phosphorylation and dephosphorylation of human myristoyltransferase type 1.
AB  - N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the
      co-translational and (or) post-translational transfer of myristate to the amino
      terminal glycine residue of a number of important proteins, especially the non
      receptor tyrosine kinases whose activity is important for tumorigenesis. Human
      NMT was found to be phosphorylated by non-receptor tyrosine kinase family members
      of Lyn, Fyn, and Lck and dephosphorylated by the Ca2+/calmodulin-dependent
      protein phosphatase, calcineurin. In this review, we discuss the cross-talk that
      exists between NMT and their N-myristoylated protein substrates. The cross-talk
      among NMT, tyrosine kinases, and phosphatases may be determined by their
      subcellular localization and by the physiological state of the cell.

PMID- 16998535
TI  - Transcriptional regulation by insulin: from the receptor to the gene.
AB  - Insulin, after binding to its receptor, regulates many cellular processes and the
      expression of several genes. For a subset of genes, insulin exerts a negative
      effect on transcription; for others, the effect is positive. Insulin controls
      gene transcription by modifying the binding of transcription factors on insulin
      response elements or by regulating their transcriptional activities. Different
      insulin-signaling cascades have been characterized as mediating the insulin
      effect on gene transcription. In this review, we analyze recent data on the
      molecular mechanisms, mostly in the liver, through which insulin exerts its
      effect. We first focus on the key transcription factors (viz. Foxo, sterol
      response-element-binding protein family (SREBP), and Sp1) involved in the
      regulation of gene transcription by insulin. We then present current information
      on the way insulin downregulates and upregulates gene transcription, using as
      examples of downregulation phosphoenolpyruvate carboxykinase (PEPCK) and insulin
      like growth factor binding protein 1 (IGFBP-1) genes and of upregulation the
      fatty acid synthase and malic enzyme genes. The last part of the paper focuses on
      the signaling cascades activated by insulin in the liver, leading to the
      modulation of gene transcription.

PMID- 16998536
TI  - Regulating insulin signaling and beta-cell function through IRS proteins.
AB  - Diabetes mellitus is a complex disorder that arises from various causes,
      including dysregulated glucose sensing and impaired insulin secretion (maturity
      onset diabetes of youth, MODY), autoimmune-mediated beta-cell destruction (type
      1), or insufficient compensation for peripheral insulin resistance (type 2). Type
      2 diabetes is the most prevalent form that usually occurs at middle age; it
      afflicts more than 30 million people over the age of 65, but is appearing with
      greater frequency in children and adolescents. Dysregulated insulin signaling
      exacerbated by chronic hyperglycemia promotes a cohort of systemic disorders-
      including dyslipidemia, hypertension, cardiovascular disease, and female
      infertility. Understanding the molecular basis of insulin resistance can prevent
      these disorders and their inevitable progression to type 2 diabetes.

PMID- 16998537
TI  - Enhanced expression of Gialpha protein and adenylyl cyclase signaling in aortas
      from 1 kidney 1 clip hypertensive rats.
AB  - We have previously shown the augmented levels of Gialpha-2 and Gialpha-3 proteins
      (isoforms of inhibitory guanine nucleotide regulatory protein (G-protein)), and
      not of Gsalpha, in the hearts and aortas of spontaneously and experimentally
      induced hypertensive rats. The increased expression of Gialpha and blood pressure
      was restored toward WKY levels by captopril treatment, suggesting a role for
      angiotensin (Ang) II in the enhanced expression of Gialpha protein and blood
      pressure. This study was undertaken to investigate whether 1 kidney 1 clip (1K
      1C) hypertensive rats that exhibit enhanced levels of Ang II also express
      enhanced levels of Gialpha proteins. Aortas from 1K-1C hypertensive rats were
      used. The expression of G-proteins was determined at protein levels with
      immunoblotting techniques, using specific antibodies for different isoforms of G
      proteins. The levels of Gialpha-2 and Gialpha-3 proteins were significantly
      higher in aortas from 1K-1C hypertensive rats than in control rats; Gsalpha
      levels were unchanged. The inhibitory effect of low concentrations of guanosine
      5'-[gamma-thio]triphosphate (GTPgammaS) on forskolin (FSK)-stimulated adenylyl
      cyclase (AC) activity was significantly enhanced in aortas from 1K-1C
      hypertensive rats; the inhibitory effect of C-ANP(4-23), which specifically
      interacts with the atrial natriuretic peptide (ANP)-C receptor, and Ang II on AC
      was attenuated. GTPgammaS, isoproterenol, glucagon, NaF, and FSK stimulated the
      AC activity in aortas from control and hypertensive rats to varying degrees;
      however, the stimulations were significantly lower in hypertensive rats than in
      control rats. These data suggest that aortas from 1K-1C hypertensive rats exhibit
      enhanced expression of Gialpha proteins and associated functions.

PMID- 16998538
TI  - Differential changes in beta-adrenoceptor signal transduction in left and right
      ventricles of infarcted rats.
AB  - Although different experimental and clinical studies have revealed varying
      degrees of defects in beta-adrenoceptors (beta-ARs) during the development of
      heart failure, the mechanisms for differences in beta-AR signal transduction
      between the left (LV) and right ventricle (RV) are not understood. Because
      biochemical alterations in the myocardium depend on the stage of heart disease,
      this study was undertaken to assess the status of beta-ARs in the LV and RV at
      different stages of heart failure. Myocardial infarction was induced in rats by
      occluding the left coronary artery for 8 and 24 weeks. The beta-AR signal
      transduction was monitored by measuring beta1-AR density, the isoproterenol
      induced positive inotropic effect, the increase in [Ca2+]i in cardiomyocytes, and
      the activation of adenylyl cyclase. The beta-AR signal transduction parameters in
      the 8- and 24-week failing LV were depressed, whereas the RV showed upregulation
      at 8 weeks and downregulation at 24 weeks of these mechanisms. These results
      suggest that beta-AR-mediated signal transduction in the LV and RV are
      differentially regulated and are dependent upon the stage of development of
      congestive heart failure due to myocardial infarction.

PMID- 16998539
TI  - Altered glucose homeostasis in mice lacking the receptor protein tyrosine
      phosphatase sigma.
AB  - Several protein tyrosine phosphatases (PTPs) expressed in insulin sensitive
      tissues are proposed to attenuate insulin action and could act as key regulators
      of the insulin receptor (IR) signaling pathway. Among these PTPs, RPTPsigma is
      expressed in relatively high levels in insulin-target tissues. We show that
      RPTPsigma-/- knockout mice have reduced plasma glucose and insulin concentrations
      in the fasted state compared with their wild-type siblings. The knockout animals
      were also more sensitive to exogenous insulin as assayed by insulin-tolerance
      tests. Despite increased whole-body insulin sensitivity, tyrosine phosphorylation
      of the IR was not increased in muscle of RPTPsigma-/- animals, as would be
      expected in insulin-sensitive animals. Instead, the levels of IR tyrosine
      phosphorylation and PI3-kinase activity were reduced in the muscle of knockout
      animals stimulated with insulin in vivo. However, insulin-stimulated Akt serine
      phosphorylation was essentially identical between both groups of mice.
      Accordingly, muscles isolated from RPTPsigma-/- mice did not have a significant
      increase in glucose uptake in response to insulin, suggesting that RPTPsigma did
      not play a direct role in this process. Taken together, our results suggest an
      indirect modulation of the IR signaling pathways by RPTPsigma. Since low dose
      injection of growth hormone (GH) normalized the response to exogenous insulin in
      RPTPsigma-/- mice, we propose that the insulin hypersensitivity observed in
      RPTPsigma-/- mice is secondary to their neuroendocrine dysplasia and GH/IGF-1
      deficiency.

PMID- 16998540
TI  - Vanadyl(IV) complexes with saccharides. Bioactivity in osteoblast-like cells in
      culture.
AB  - Complexes of vanadyl(IV) with 4 monosaccharides and 5 disaccharides were tested
      in 2 osteoblast-like cell lines (MC3T3E1 and UMR106). Many complexes caused
      stimulation of UMR106 proliferation (120% basal) in the range of 2.5 to 25
      micromol/L. In the nontransformed osteoblasts, some vanadyl-saccharide complexes
      stimulated the mitogenesis (115% basal) in the same range of concentration. The
      glucose and sucrose complexes were the most efficient inhibitory agents (65% and
      88% of inhibition vs. basal, respectively) for tumoral cells at 100 micromol/L.
      The galactose and turanose complexes exerted a similar effect in the
      nontransformed osteoblasts. On the other hand, all the complexes promoted the
      phosphorylation of the extracellular regulated kinases (ERKs). All together,
      these results indicate that the stimulation of ERKs is not the only factor that
      plays a role in the proliferative effects of vanadium derivatives since some
      compounds were inhibitory proliferating agents. Cell differentiation was
      evaluated by alkaline phosphatase specific activity and collagen synthesis in
      UMR106 cells. All the complexes inhibited alkaline phosphatase activity, with
      galactose complex as the most effective compound (IC50 = 43 micromol/L). The
      complex with the trehalose TreVO was the most effective agent to stimulate
      collagen synthesis (142% basal) and glucose consumption (132% basal). A cytosolic
      tyrosine protein kinase and the kinase-3 of glycogen synthase seem to be involved
      in the stimulation of glucose consumption by vanadium derivatives. In this
      series, only TreVO gathered the characteristics of a good insulin mimetic and
      osteogenic drug. In addition, this complex was a good promoting agent of
      nontransformed osteoblast proliferation, whereas it inhibited tumoral
      osteoblasts. GluVO, the complex with glucose, was also more toxic for tumoral
      than for nontransformed cells. These 2 vanadium derivatives are good potential
      antitumoral drugs. All the results suggest that the biological effects of
      vanadium compounds are a complex phenomenon influenced by the complexation, the
      dose, and the nature of the ligands and the cells.

PMID- 16998541
TI  - Activation of insulin-like growth factor type-1 receptor is required for H2O2
      induced PKB phosphorylation in vascular smooth muscle cells.
AB  - Evidence accumulated in recent years has revealed a potential role for reactive
      oxygen species (ROS) in the pathophysiology of cardiovascular diseases. However,
      the precise mechanisms by which ROS contribute to the development of these
      diseases are not fully established. Previous work from our laboratory has
      indicated that exogenous hydrogen peroxide (H2O2) activates several signaling
      protein kinases, such as extracellular signal-regulated kinase 1 and 2 (ERK1/2)
      and protein kinase B (PKB) in A10 vascular smooth muscle cells (VSMC). However,
      the upstream elements responsible for this activation remain unclear. Although a
      role for epidermal growth factor receptor (EGFR) protein tyrosine kinase (PTK) in
      H2O2-induced ERK1/2 signaling has been suggested, the contribution of this PTK or
      other receptor or nonreceptor PTKs to PKB activation is not well defined in VSMC.
      In this study, we used pharmacological inhibitors to investigate the role of
      receptor and Src-family-PTKs in H2O2-induced PKB phosphorylation. AG1478, a
      specific inhibitor of EGFR, failed to attenuate the H2O2-induced increase in PKB
      Ser473 phosphorylation, whereas AG1024, an inhibitor of insulin-like growth
      factor type1 receptor (IGF-1R)-PTK, almost completely blocked this response. H2O2
      treatment also enhanced tyrosine phosphorylation of the IGF-1Rbeta subunit, which
      was significantly inhibited by AG1024 pretreatment of cells. Furthermore,
      pharmacological inhibition of Src by PP2 (4-amino-5-(4-chlorophenyl)-7-(t
      butyl)pyrazole(3,4-d) pyrimidine) decreased PKB phosphorylation. Moreover, H2O2
      induced PKB phosphorylation was associated with increased tyrosine
      phosphorylation of c-Src and Pyk2 in an AG1024- and PP2-inhibitable manner. In
      conclusion, these data provide evidence of the contribution of IGF-1R-PTK in
      initiating H2O2-evoked PKB phosphorylation in A10 VSMC, with an intermediary role
      for c-Src and Pyk2 in this process.

PMID- 16998542
TI  - ETB receptor dependent alteration in aortic responses to ET-1 in the
      cardiomyopathic hamster.
AB  - The aim of this study was to verify whether an alteration in the aortic
      endothelin-1 (ET-1) response takes place in UM-X7.1 cardiomyopathic hamsters. Our
      results showed that ET-1 (10(-12) - 10(-5) mol/L) induces dose-dependent
      sustained increases in tension in the intact and endothelium denuded aortas from
      both normal and cardiomyopathic hamsters. The EC50 values of ET-1 of both intact
      and endothelium denuded aortas of normal hamsters were similar (2.2 x 10(-9)
      mol/L and 1.8 x 10(-9) mol/L, respectively). However, in cardiomyopathic
      hamsters, the EC50 of ET-1 in intact aortas was higher (1.5 x 10(-8) mol/L) than
      that of the endothelium denuded preparations (2.7 x 10(-9) mol/L). The EC50 of ET
      1 in normal and cardiomyopathic hamster denuded aortas were similar. However, the
      EC50 of ET-1 in intact aortas of cardiomyopathic hamster was higher (1.5 x 10(-8)
      mol/L) than that of normal hamsters (2.2 x 10(-9) mol/L). Pre-treatment with the
      ETA receptor antagonist ABT-627 (10(-5)mol/L) of intact and endothelium denuded
      aortas from both normal and cardiomyopathic hamsters significantly prevented ET-1
      (10(-7) mol/L) from inducing an increase in tension. Pre-treatment with the ETB
      receptor antagonist A-192621 (10(-5) mol/L) had no effect on the ET-1-induced
      increase in tension in endothelium denuded aortas of both normal and
      cardiomyopathic hamsters, as well as in intact preparations of normal animals.
      However, blockade of the ETB receptors in intact aortas of cardiomyopathic
      hamsters significantly (p < 0.001) potentiated the ET-1-induced increase in
      tension. In summary, an attenuation of the contraction response to ET-1 was found
      in UM-X7.1 cardiomyopathic hamsters when compared with normal age-matched
      hamsters. This alteration of the ET-1 effect in the aortas of cardiomyopathic
      hamsters seems to be dependent on the presence of the endothelium and could be
      due, in part, to an increase in the contribution of endothelial ETB receptors to
      relaxation, which in turn acts as a physiological depressor of ET-1
      vasoconstriction. Our results suggest that an increase in the endothelium ETB
      receptor density may play a role in the development of hypotension in UM-X7.1
      cardiomyopathic hamsters.

PMID- 16998543
TI  - [On an old tract].

PMID- 16998544
TI  - [Customized drugs?].

PMID- 16998545
TI  - [On family practice's own premises].

PMID- 16998546
TI  - [New rights--always good?].

PMID- 16998547
TI  - [High incidence of work-related disease among asthmatics on sick-leave].
AB  - BACKGROUND: We have previously shown that work-related asthma is substantially
      underreported and usually not notified to the Labour Inspection Authority until
      it has become chronic and interferes with future work. The aim of this study was
      to evaluate whether conditions relating to individuals are important for the
      susceptibility to work-related asthma and to assess whether there is a
      correspondence between patients' and physicians' perception of the importance of
      exposure to work in relation to the disease. MATERIAL AND METHODS: Questionnaires
      were sent to 824 workers (56% women) aged 18-55 years, who had been on sick leave
      > 16 days in the years 2000-2003. The disease was classified as work-related
      asthma if the following questions were answered positively: "Have you ever had
      respiratory symptoms in relation to your work?" and "Did the symptoms improve on
      absence from work?" RESULTS: The response rate was 72%, 58% of the responders
      were women. 416 (70%) had work-related asthma. There were fewer smokers in the
      group with work-related asthma than among those without, atopy was equally
      prevalent. Occupational titles reflected the gender differences of the Norwegian
      labour force. Indoor climate at the workplace was stated as the most frequent
      provoking factor. The physicians suspected a relationship to work for about half
      of the 416, notification was only sent for 21% of the male and 10% of the female
      employees. INTERPRETATION: The importance of occupational exposure seems to be
      underestimated, especially for women with asthma. Neither atopy nor smoking
      increased the risk for work-related symptoms. Indoors climate at the work place
      was most often given as the reason for work-related symptoms. A reduction of
      exposure led to a reduction of symptoms for most individuals.

PMID- 16998548
TI  - [Vitiligo--loss of cutaneous pigmentation].
AB  - BACKGROUND: Vitiligo is an acquired pigmentary skin disorder that affects 0.5-2%
      of the population. Many patients contact their physician and alternative
      therapists for help. This review article presents an update of knowledge about
      vitiligo and is aimed at physicians that treat this patient group. METHOD: The
      article is based on literature identified on PubMed, textbooks in Dermatology and
      supplemented by clinical experience. RESULTS AND INTERPRETATION: Vitiligo is
      characterized by the absence of melanocytes in skin and hair follicles. The
      pathogenesis is complex with genetic, autoimmune and toxic contributors.
      Clinically well-defined milk-white maculae are seen in the skin, with a wide
      variety of spread and distribution. The debut of vitiligo is often in childhood
      and adolescence. Investigations indicate that vitiligo affects quality in life
      for both children and adults. Treatment of vitiligo is a challenge. Phototherapy
      with narrowband UVB or topical therapy with tacrolimus ointment or potent
      steroids may be indicated in some cases, but the effect is not well documented.

PMID- 16998549
TI  - [Atrioventricular nodal reentry tachycardia in children].
AB  - BACKGROUND: Atrioventricular nodal reentry tachycardia is a supraventricular
      tachycardia with a double nodal pathway between the atria and the ventricles
      located in the normal AV-node. It may cause a reentry circuit. Atrioventricular
      nodal reentry tachycardia is one of the most common supraventricular tachycardias
      in adulthood, but is seldom diagnosed in children--perhaps because of
      difficulties with diagnosing them. We have studied diagnostic criteria, clinical
      presentation, incidence, prognosis and treatment in children and adolescents.
      METHODS: The article is based on the literature found in the databases PubMed and
      Medline. We used the search words atrioventricular nodal reentry tachycardia,
      AVNRT, permanent junctional reentry tachycardia, PJRT, supraventricular
      tachycardia, neonates, infants and children. Articles were also identified by
      examining the references. RESULTS: Atrioventricular nodal reentry tachycardia is
      rare during the first years of life, but becomes more frequent with age. There
      are few studies of this rhythm disturbance in children and reliable data on
      incidence, prognosis and prognostic variables are limited, especially for
      untreated cases. There are three main treatment regimens, acute and prophylactic
      medication and curative treatment with radiofrequency catheter ablation.

PMID- 16998550
TI  - [Electronic medical handbooks--are they suitable for implementation of guidelines
      in health care?].
AB  - BACKGROUND: The Directorate for Health and Social Affairs commissioned a project
      to evaluate the distribution and use of a Norwegian electronic medical handbook
      (NEL). MATERIAL AND METHODS: NEL uses multimedia techniques and is distributed on
      a CD twice a year. A questionnaire about the use of NEL was given to 91 medical
      students. Health professionals at two hospitals and 12 health centres were
      interviewed. RESULTS: The use of the electronic handbook differed more within
      than between groups of professionals. NEL is applied for three main purposes:
      decision support, quality assurance and as a source for information pamphlets
      designed for patients. The professionals believed that NEL has contributed to
      patients' receiving more information and more uniform treatment. Criticism was
      made about the price and for the lack of integration with the electronic patient
      record. INTERPRETATION: The study has revealed some barriers to implementation
      and use of electronic information sources. Under certain circumstances an
      electronic handbook might be suitable way for authorities and others to
      distribute professional guidelines.

PMID- 16998551
TI  - [Surgical treatment of solid malignant tumours in childhood].
AB  - BACKGROUND: Surgery is an important part of the multidisciplinary treatment of
      solid malignant tumours in childhood. This article gives an update on the types
      and numbers of tumour operations in Paediatric Surgical Service, Department of
      Surgery, Rikshospitalet. The presentation is restricted to the surgical part of
      the treatment; data on chemotherapy and irradiation are not included. MATERIAL
      AND METHODS: Epidemiological data are presented for all patients treated
      surgically for malignant - or potentially malignant tumours during the 20 years
      from 1985 to 2004 in our department. Survival data have been checked with the
      Public Registry (Folkeregisteret). RESULTS: 341 operations have been performed in
      310 patients. 58% of the patients came from the regional health enterprise for
      southern Norway, where Rikshospitalet is located, and 42% came from the other 4
      Norwegian health regions. Since 1993, 30 of 203 patients have been referred from
      the other 4 regional hospitals. There was no perioperative mortality, but 3
      patients died during the first postoperative month. 85% of the patients were
      alive in January 2006. The survival rates for the individual tumours ranged from
      100% for ovarian tumours and 98% for Wilms' tumour to 62% for neuroblastoma.
      INTERPRETATION: The Paediatric Surgical Service at Rikshospitalet has operated
      solid malignant tumours in children from all parts of Norway. A large spectrum of
      tumours have been treated without operative mortality.

PMID- 16998552
TI  - [Daptomycin--a new antibiotic for the treatment of skin and soft tissue
      infections].
AB  - Daptomycin (Cubicin) is a bactericidal lipopeptide antibiotic that was approved
      in February 2006 for the European market, including Norway, for the treatment of
      patients with complicated skin and soft tissue infections caused by Gram-positive
      cocci. Daptomycin is administered intravenously and eliminated mainly by the
      kidneys. Dose reduction is therefore necessary in patients with impaired renal
      function. The drug is active only against Gram-positive cocci. Daptomycin therapy
      of patients with complicated skin and soft tissue infections caused by Gram
      positive cocci, is as effective as standard therapy with intravenous semi
      synthetic penicillin or vancomycin. The agent is usually well tolerated, but side
      effects in skeletal muscles are more prevalent than with semi-synthetic
      penicillins or vancomycin. To prevent development of daptomycin resistance, the
      agent should be reserved for the treatment of patients with infections caused by
      Staphylococcus aureus that are resistant to antibiotics commonly used for the
      treatment of skin and soft tissue infections, e.g. penicillins or clindamycin.

PMID- 16998553
TI  - [Customized drug therapy--how near is the goal?].
AB  - BACKGROUND: During the last years we have gained considerable knowledge , about
      genetic factors behind the huge inter-individual variation in drug response and
      the risk of adverse drug reactions. MATERIAL AND METHODS: The article is based
      upon a recent search in PubMed and the author's own studies and experience with
      genotyping related to drug therapy. RESULTS AND INTERPRETATION: A considerable
      genetic variability has been revealed both in the function of drug-metabolising
      enzymes, transport proteins participating in drug distribution and excretion, and
      drug targets. This variability may be important for the choice and dosage of a
      drug. A number of genotyping methods are available for routine pharmacogenetic
      testing today. In some cases, genotyping is helpful before start of drug therapy,
      while in other cases genotyping is not indicated before a clinical problem has
      arisen and needs treatment. Although there are some clear-cut examples of
      genotyping being important for customising drug treatment, the next decades will
      determine whether genotyping will make it possible to predict treatment response
      as a general principle before starting drug therapy.

PMID- 16998554
TI  - [Dosaging of proton pumps inhibitors].

PMID- 16998555
TI  - [Pharmacogenetics and tailored drug treatment in schizophrenia].
AB  - BACKGROUND: Medical treatment of psychiatric disorders is often characterised by
      trial and error. Psychotropic drugs show a large variation in response and side
      effects. Molecular genetic techniques seem to have a potential for identifying
      biological predictors of drug response and side effects, and help to establish
      tailored drug treatment. MATERIAL AND METHODS: Based on relevant literature and
      own research, this article gives a short overview of some pharmacogenetic aspects
      related to pharmacological treatment of schizophrenia. RESULTS: Antipsychotic and
      antidepressive drugs are metabolized by many different enzymes in the cytochrome
      P450 system. The rate of the drug-metabolism depends to some extent on genetic
      variants, and several gene-variants affect the serum level of the drugs, which
      may cause side effects or non-response. Several pharmacogenetic studies have
      indicated that both the therapeutic response and the level of motor and metabolic
      side effects of antipsychotic drug treatment of schizophrenia are related to
      polymorphisms in the serotonine and dopamine receptor genes, but there are
      conflicting findings. INTERPRETATION: However, most of these data remain
      preliminary, and so far pharmacogenetics has been of little practical help for
      clinical psychiatry. Due to the progress in molecular genetics and improved
      quality of clinical studies, there is a hope that a new generation of psychiatric
      pharmacogenetic studies will provide us with more useful information for drug
      treatment of schizophrenia and other psychiatric conditions.

PMID- 16998556
TI  - [What part does patient's family history have in tomorrow's medicine?].

PMID- 16998557
TI  - [Go round with a collection box!].

PMID- 16998560
TI  - [Stated conflict of interest].

PMID- 16998561
TI  - [Warfarin treatment in atrial fibrillation].

PMID- 16998567
TI  - [Princess was her name and she was only 7 years old].

PMID- 16998569
TI  - Confirming a diagnosis of hereditary colorectal cancer: the impact of a Familial
      Bowel Cancer Registry in New Zealand.
AB  - AIMS: The optimal management of familial bowel cancer is thought to involve
      specialised familial cancer units and registries that facilitate a
      multidisciplinary approach. We studied the impact this approach had on the
      investigation and management of affected families in our register. METHOD: A
      review of the outcomes of assessment for 25 families was undertaken. These
      families have completed assessment by the Northern Regional Genetic Service
      Familial Bowel Cancer Registry because of the possibility of a hereditary bowel
      cancer syndrome. Details of the cancer history and screening advice known at the
      time of initial referral to the genetic service, and at the end of assessment,
      were compared. RESULTS: Detailed family history revealed 130 cancers, 90 of which
      were known at referral. Eighty-four cancers were confirmed, of which 73 belonged
      to the spectrum of cancers associated with hereditary nonpolyposis colorectal
      cancer (HNPCC). The mean age of diagnosis was 56.3 years. Eight families met the
      modified Amsterdam Criteria for the diagnosis of HNPCC, compared to four families
      at the time of referral. Familial hyperplastic polyposis was diagnosed in one
      family. 164 asymptomatic at-risk first-degree relatives were identified, 48 from
      families who met the Amsterdam criteria and were thereby recommended to have
      intensive colonoscopic screening. CONCLUSION: Assessment by the Familial Bowel
      Cancer Registry increased the number of cancers identified in families, thus
      facilitating a diagnosis of HNPCC in a third of the referred families and a
      diagnosis of hyperplastic polyposis in one other. Consequently specialised
      genetic testing and intensive colonoscopic surveillance could be targeted to the
      asymptomatic first-degree relatives most at risk. Ongoing coordination of
      colonoscopic surveillance by the registry for those individuals identified to
      have disease causing mutations or to be at-risk, is anticipated to reduce the
      number of deaths from colorectal cancer in these families.

PMID- 16998570
TI  - The control of melanoma in New Zealand.
AB  - AIMS: This study estimated the impact of prevention, screening, early diagnosis,
      and treatment on the burden of melanoma in New Zealand. METHODS: Cancer control
      plans and management guidelines were reviewed to identify activities that could
      reduce the burden of melanoma in New Zealand and an estimation was made of their
      effects on incidence and mortality. The base year for estimating changes in
      incidence and mortality was the published melanoma data for 2002. RESULTS: The
      registration of melanoma increased from 1037 new registrations in 1993 to 1487 in
      1994 and peaked at 1759 in 1995. In 2002 a further increase occurred, to 1842 new
      registrations and 235 deaths from melanoma. It is likely that 328 of the 1842 new
      cases of melanoma in 2002 were directly attributable to severe sunburn. A
      reduction of 10% in the number of people getting severely sunburnt could prevent
      28 melanoma cases per year. If 2% of melanoma deaths occur in high-risk
      individuals, approximately 4 deaths per year could be prevented by surveillance
      of high-risk groups. Thin melanoma has a very good prognosis: a 10% shift in the
      depth distribution into the thinnest depth category would result in about 29
      deaths from melanoma prevented each year. CONCLUSIONS: The best avenues for
      reducing the burden of melanoma in New Zealand are prevention of excessive sun
      exposure and early diagnosis. Reducing severe sunburn and diagnosing a greater
      proportion of melanomas when they are thin would have the greatest impact on the
      incidence of and mortality from melanoma.

PMID- 16998571
TI  - Back to the future: postoperative pain management beyond COX-2 inhibitors.
AB  - In the aftermath of the heated dispute on COX-2 selective nonsteroidal anti
      inflammatory drugs (NSAID) that led to the national and international withdrawal
      of several of the recently introduced coxibs, a balanced discussion of pros and
      cons for their short term use is warranted. Further debate and research has
      highlighted risks with both classical NSAIDs and coxibs when administered to
      patients with cardiovascular disease. For several decades discussion about
      indications, risks and contraindications for the perioperative use of classical
      NSAIDs has been ongoing. The COX debate has further added some uncertainty
      amongst practitioners. With a vast amount of research available on this topic, it
      should however be feasible to reach some consensus for the perioperative use of
      NSAIDs as well as for coxibs. This would ensure that the right patients take
      advantage of our present knowledge of NSAIDs as part of a multimodal and balanced
      perioperative analgesic regimen and at the same time that the patients at risk
      are not prescribed such drugs. Rational use of NSAIDs in the perioperative period
      would benefit a major group of patients who at present are deprived of such
      therapy due to unfounded fears of side effects and lack of knowledge among
      prescribers. This review highlights some of the aspects of short term (i.e. less
      than 5 days) perioperative use of NSAIDs.

PMID- 16998572
TI  - Improving outcomes in ovarian cancer.

PMID- 16998573
TI  - Melanoma control: few answers, many questions.

PMID- 16998574
TI  - Managing squamous cell carcinoma of the bulbomembranous male urethra with genital
      preserving surgery and chemoradiotherapy.

PMID- 16998575
TI  - Quality improvement in New Zealand healthcare. Part 6: keeping the patient front
      and centre to improve healthcare quality.
AB  - Patient-centred care is arguably the most important of the dimensions of quality
      as it is likely that a healthcare system which is patient-centred will also
      perform well against the other dimensions--safety as well as timely, accessible,
      effective, and efficient care. What does it mean to be patient-centred and how
      can it be achieved? This article explores several definitions of patient-centred
      care and discusses two interpretations--the expert patient and shared decision
      making. Being sick is inherently a vulnerable position to be in and our current
      healthcare system does little to recognise and alleviate this vulnerability. But
      the patient-centred approach is about more than making the journey for patients
      less tortuous, it has actually been shown to improve outcomes. The evidence of
      benefit for a patient-centred approach is reviewed, along with some of the
      challenges in implementing the concept in practice.

PMID- 16998576
TI  - Osteosarcoma in New Zealand: an outcome study comparing survival rates between
      1981-1987 and 1994-1999.
AB  - AIMS: To review the data and outcome of patients with osteosarcoma in New Zealand
      from 1994 to 1999 and to compare this to data retrieved from a similar study from
      1981 to 1987. METHODS: Data from 1994-1999 was obtained from the New Zealand
      Cancer Registry; raw data was also retrieved from the 1981-1987 study. RESULTS:
      There were 96 cases in the 1981-1987 cohort and 84 cases in the 1994-1999 cohort.
      Overall, 5-year survival from osteosarcoma improved from 32.3% to 44.0% between
      the cohorts. When the cohorts were compared, there was a trend toward improved
      outcome in most subgroups CONCLUSIONS: The outcome in patients with osteosarcoma
      in New Zealand has improved over the study period and is similar to that seen in
      the overseas literature.

PMID- 16998577
TI  - Palliative Care Partnership: a successful model of primary/secondary integration.
AB  - The health reforms of the 1990s and early 21st century have seen unheralded
      change in the delivery of health services in New Zealand, and the concept of
      integration of primary and specialist or secondary services into a seamless
      health delivery service is one of the key planks of national and regional
      healthcare planning in New Zealand. This paper reports on a successful primary
      secondary integration project. Starting with commentary on the historical
      difficulties that acted as a catalyst to this initiative, it reports on the
      development process, how the model works in practice, and outlines some initial
      evaluation work done as part of its quality improvement component. Given the
      collaborative nature of this project and its scope across primary and specialist
      care sectors, the authors believe this model has implications and relevance
      across a wide spectrum of the New Zealand health service.

PMID- 16998578
TI  - Medical image. Extensive oral ulcerations.

PMID- 16998579
TI  - Multidisciplinary treatment of colorectal cancer in New Zealand: survival rates
      from 1997-2002.
AB  - INTRODUCTION: The surgical and oncological treatment of colorectal cancer has
      undergone steady evolution over the last 20 years, however nationally derived
      survival figures have been disappointingly slow to improve. This study is an
      analysis of prospectively collected data (taken over a 6-year period) on the
      outcome of colorectal cancer management from a single university surgical unit in
      New Zealand. METHODS: A comprehensive dataset was prospectively collected on all
      patients seen with colorectal cancer by a single surgical team, and complete
      follow-up was obtained. Details of surgical and oncology treatment of the primary
      lesion and of any subsequent disease and treatment were recorded. Survival was
      analysed by clinical and pathological variables. RESULTS: Over 6 years, 244 new
      patients with a total of 263 primary colorectal cancers were seen.; 97% of these
      patients had an operation and 95% had the primary tumour resected. The mortality
      after elective operation was 0.5% (1/197) and 8% (3/39) after urgent or emergency
      surgery. After a median follow-up of 32 months, recurrence in the pelvis was
      apparent in 1 of 72 patients after curative resection of rectal cancer and 4 of
      18 after palliative resection, thus giving a total pelvic recurrence rate of 6%
      at 30 months. The 5-year survival rate of all new patients seen with a rectal
      cancer was 58% and 56.5 % for patients with a colon cancer. CONCLUSIONS: A
      combination of low operative mortality rates, low local recurrence rates in
      rectal cancer, the increasing use of adjuvant therapies, and careful follow up to
      detect (and where possible resect) metastatic disease at an early stage is
      associated with good cancer-specific survival figures. However further
      improvement in survival will need a shift to earlier stage at diagnosis and more
      effective chemotherapy (both in the adjuvant setting and for advanced disease) if
      significant gains in survival are to be made.

PMID- 16998580
TI  - Modern treatment for cholecystostomy.

PMID- 16998581
TI  - New Zealand should control Campylobacter in fresh poultry before worrying about
      flies.

PMID- 16998582
TI  - What is health?

PMID- 16998583
TI  - Fluid resuscitation in malaria: the need for new randomised clinical trials.

PMID- 16998584
TI  - Volume expansion with albumin compared to gelofusine in children with severe
      malaria: results of a controlled trial.
AB  - OBJECTIVES: Previous studies have shown that in children with severe malaria,
      resuscitation with albumin infusion results in a lower mortality than
      resuscitation with saline infusion. Whether the apparent benefit of albumin is
      due solely to its colloidal properties, and thus might also be achieved with
      other synthetic colloids, or due to the many other unique physiological
      properties of albumin is unknown. As albumin is costly and not readily available
      in Africa, examination of more affordable colloids is warranted. In order to
      inform the design of definitive phase III trials we compared volume expansion
      with Gelofusine (succinylated modified fluid gelatin 4% intravenous infusion)
      with albumin. DESIGN: This study was a phase II safety and efficacy study.
      SETTING: The study was conducted at Kilifi District Hospital, Kenya.
      PARTICIPANTS: The participants were children admitted with severe falciparum
      malaria (impaired consciousness or deep breathing), metabolic acidosis (base
      deficit > 8 mmol/l), and clinical features of shock. INTERVENTIONS: The
      interventions were volume resuscitation with either 4.5% human albumin solution
      or Gelofusine. OUTCOME MEASURES: Primary endpoints were the resolution of shock
      and acidosis; secondary endpoints were in-hospital mortality and adverse events
      including neurological sequelae. RESULTS: A total of 88 children were enrolled:
      44 received Gelofusine and 44 received albumin. There was no significant
      difference in the resolution of shock or acidosis between the groups. Whilst no
      participant developed pulmonary oedema or fluid overload, fatal neurological
      events were more common in the group receiving gelatin-based intervention fluids.
      Mortality was lower in patients receiving albumin (1/44; 2.3%) than in those
      treated with Gelofusine (7/44; 16%) by intention to treat (Fisher's exact test, p
      = 0.06), or 1/40 (2.5%) and 4/40 (10%), respectively, for those treated per
      protocol (p = 0.36). Meta-analysis of published trials to provide a summary
      estimate of the effect of albumin on mortality showed a pooled relative risk of
      death with albumin administration of 0.19 (95% confidence interval 0.06-0.59; p =
      0.004 compared to other fluid boluses). CONCLUSIONS: In children with severe
      malaria, we have shown a consistent survival benefit of receiving albumin
      infusion compared to other resuscitation fluids, despite comparable effects on
      the resolution of acidosis and shock. The lack of similar mortality benefit from
      Gelofusine suggests that the mechanism may involve a specific neuroprotective
      effect of albumin, rather than solely the effect of the administered colloid.
      Further exploration of the benefits of albumin is warranted in larger clinical
      trials.

PMID- 16998585
TI  - Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial
      regulation involving adhesion and cytokine signaling.
AB  - Tight regulation of COX-2 expression is a key feature controlling eicosanoid
      production in atherosclerosis and other inflammatory syndromes. Adhesive
      interactions between platelets and monocytes occur in these conditions and
      deliver specific signals that trigger inflammatory gene expression. Using a
      cellular model of monocyte signaling induced by activated human platelets, we
      identified the central posttranscriptional mechanisms that regulate timing and
      magnitude of COX-2 expression. Tethering of monocytes to platelets and to
      purified P-selectin, a key adhesion molecule displayed by activated platelets,
      induces NF-kappaB activation and COX-2 promoter activity. Nevertheless, COX-2
      mRNA is rapidly degraded, leading to aborted protein synthesis. Time-dependent
      signaling of monocytes induces a second phase of transcript accumulation
      accompanied by COX-2 enzyme synthesis and eicosanoid production. Here, generation
      of IL-1beta, a proinflammatory cytokine, promoted stabilization of COX-2 mRNA by
      silencing of the AU-rich mRNA decay element (ARE) in the 3'-untranslated region
      (3'UTR) of the mRNA. Consistent with observed mRNA stabilization, activated
      platelets or IL-1beta treatment induced cytoplasmic accumulation and enhanced ARE
      binding of the mRNA stability factor HuR in monocytes. These findings demonstrate
      that activated platelets induce COX-2 synthesis in monocytes by combinatorial
      signaling to transcriptional and posttranscriptional checkpoints. These
      checkpoints may be altered in disease and therefore useful as targets for
      antiinflammatory intervention.

PMID- 16998586
TI  - Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in
      vivo model of human placentation.
AB  - We studied the vascular effects of invasive human cytotrophoblasts in vivo by
      transplanting placental villi to the fifth mammary fat pads or beneath the kidney
      capsules of Scid mice. Over 3 weeks, robust cytotrophoblast invasion was observed
      in both locations. The architecture of the mammary fat pad allowed for detailed
      analysis of the cells' interactions with resident murine blood vessels, which
      revealed specific induction of apoptosis in the endothelial cells and smooth
      muscle walls of the arterioles. This finding, and confirmation of the results in
      an in vitro coculture model, suggests that a parallel process is important for
      enabling cytotrophoblast endovascular invasion during human pregnancy.
      Cytotrophoblast invasion of the kidney parenchyma was accompanied by a robust
      lymphangiogenic response, while in vitro, the cells stimulated lymphatic
      endothelial cell migration via the actions of VEGF family members, FGF, and TNF
      alpha. Immunolocalization analyses revealed that human pregnancy is associated
      with lymphangiogenesis in the decidua since lymphatic vessels were not a
      prominent feature of the nonpregnant endometrium. Thus, the placenta triggers the
      development of a decidual lymphatic circulation, which we theorize plays an
      important role in maintaining fluid balance during pregnancy, with possible
      implications for maternal-fetal immune cell trafficking.

PMID- 16998587
TI  - Calcineurin/Nfat signaling is required for perinatal lung maturation and
      function.
AB  - Pulmonary surfactant proteins and lipids are required for lung function after
      birth. Lung immaturity and resultant surfactant deficiency cause respiratory
      distress syndrome, a common disorder contributing to morbidity and mortality in
      preterm infants. Surfactant synthesis increases prior to birth in association
      with formation of the alveoli that mediate efficient gas exchange. To identify
      mechanisms controlling perinatal lung maturation, the Calcineurin b1 (Cnb1) gene
      was deleted in the respiratory epithelium of the fetal mouse. Deletion of Cnb1
      caused respiratory failure after birth and inhibited the structural maturation of
      the peripheral lung. Synthesis of surfactant and a lamellar body-associated
      protein, ABC transporter A3 (ABCA3), was decreased prior to birth. Nuclear factor
      of activated T cells (Nfat) calcineurin-dependent 3 (Nfatc3), a transcription
      factor modulated by calcineurin, was identified as a direct activator of Sftpa,
      Sftpb, Sftpc, Abca3, Foxa1, and Foxa2 genes. The calcineurin/Nfat pathway
      controls the morphologic maturation of lungs prior to birth and regulates
      expression of genes involved in surfactant homeostasis that are critical for
      adaptation to air breathing.

PMID- 16998588
TI  - Transcription factor MITF regulates cardiac growth and hypertrophy.
AB  - High levels of microphthalmia transcription factor (MITF) expression have been
      described in several cell types, including melanocytes, mast cells, and
      osteoclasts. MITF plays a pivotal role in the regulation of specific genes in
      these cells. Although its mRNA has been found to be present in relatively high
      levels in the heart, its cardiac role has never been explored. Here we show that
      a specific heart isoform of MITF is expressed in cardiomyocytes and can be
      induced by beta-adrenergic stimulation but not by paired box gene 3 (PAX3), the
      regulator of the melanocyte MITF isoform. In 2 mouse strains with different MITF
      mutations, heart weight/body weight ratio was decreased as was the hypertrophic
      response to beta-adrenergic stimulation. These mice also demonstrated a tendency
      to sudden death following beta-adrenergic stimulation. Most impressively, 15
      month-old MITF-mutated mice had greatly decreased heart weight/body weight ratio,
      systolic function, and cardiac output. In contrast with normal mice, in the MITF
      mutated mice, beta-adrenergic stimulation failed to induce B-type natriuretic
      peptide (BNP), an important modulator of cardiac hypertrophy, while atrial
      natriuretic peptide levels and phosphorylated Akt were increased, suggesting a
      cardiac stress response. In addition, cardiomyocytes cultured with siRNA against
      MITF showed a substantial decrease in BNP promoter activity. Thus, for what we
      believe is the first time, we have demonstrated that MITF plays an essential role
      in beta-adrenergic-induced cardiac hypertrophy.

PMID- 16998589
TI  - Blood-brain barrier traversal by African trypanosomes requires calcium signaling
      induced by parasite cysteine protease.
AB  - In this study we investigated why bloodstream forms of Trypanosoma brucei
      gambiense cross human brain microvascular endothelial cells (BMECs), a human
      blood-brain barrier (BBB) model system, at much greater efficiency than do T. b.
      brucei. After noting that T. b. gambiense displayed higher levels of cathepsin L
      like cysteine proteases, we investigated whether these enzymes contribute to
      parasite crossing. First, we found that T. b. gambiense crossing of human BMECs
      was abrogated by N-methylpiperazine-urea-Phe-homopheylalanine-vinylsulfone
      benzene (K11777), an irreversible inhibitor of cathepsin L-like cysteine
      proteases. Affinity labeling and immunochemical studies characterized brucipain
      as the K11777-sensitive cysteine protease expressed at higher levels by T. b.
      gambiense. K11777-treated T. b. gambiense failed to elicit calcium fluxes in
      BMECs, suggesting that generation of activation signals for the BBB is critically
      dependant on brucipain activity. Strikingly, crossing of T. b. brucei across the
      BBB was enhanced upon incubation with brucipain-rich supernatants derived from T.
      b. gambiense. The effects of the conditioned medium, which correlated with
      ability to evoke calcium fluxes, were canceled by K11777, but not by the
      cathepsin B inhibitor CA074. Collectively, these in vitro studies implicate
      brucipain as a critical driver of T. b. gambiense transendothelial migration of
      the human BBB.

PMID- 16998590
TI  - Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the
      development of tertiary lymphoid structures in the thyroid.
AB  - Ectopic expression of CC chemokine ligand 21 (CCL21) in the thyroid leads to
      development of lymphoid structures that resemble those observed in Hashimoto
      thyroiditis. Deletion of the inhibitor of differentiation 2 (Id2) gene, essential
      for generation of CD3-CD4+ lymphoid tissue-inducer (LTi) cells and development of
      secondary lymphoid organs, did not affect formation of tertiary lymphoid
      structures. Rather, mature CD3+CD4+ T cells were critical for the development of
      tertiary lymphoid structures. The initial stages of this process involved
      interaction of CD3+CD4+ T cells with DCs, the appearance of peripheral-node
      addressin-positive (PNAd+) vessels, and production of chemokines that recruit
      lymphocytes and DCs. These findings indicate that the formation of tertiary
      lymphoid structures does not require Id2-dependent conventional LTis but depends
      on a program initiated by mature CD3+CD4+ T cells.

PMID- 16998591
TI  - Myelin associated glycoprotein cross-linking triggers its partitioning into lipid
      rafts, specific signaling events and cytoskeletal rearrangements in
      oligodendrocytes.
AB  - Myelin-associated glycoprotein (MAG) has been implicated in inhibition of nerve
      regeneration in the CNS. This results from interactions between MAG and the Nogo
      receptor and gangliosides on the apposing axon, which generates intracellular
      inhibitory signals in the neuron. However, because myelin-axon signaling is
      bidirectional, we undertook an analysis of potential MAG-activated signaling in
      oligodendrocytes (OLs). In this study, we show that antibody cross-linking of MAG
      on the surface of OLs (to mimic axonal binding) leads to the redistribution of
      MAG into detergent (TX-100)-insoluble complexes, hyperphosphorylation of Fyn,
      dephosphorylation of serine and threonine residues in specific proteins,
      including lactate dehydrogenase and the beta subunit of the trimeric G-protein
      complex, and cleavage of alpha-fodrin followed by a transient depolymerization of
      actin. We propose that these changes are part of a signaling cascade in OLs
      associated with MAG function as a mediator of axon-glial communication which
      might have implications for the mutual regulation of the formation and stability
      of axons and myelin.

PMID- 16998592
TI  - Proteasome inhibitors sensitize colon carcinoma cells to TRAIL-induced apoptosis
      via enhanced release of Smac/DIABLO from the mitochondria.
AB  - The synergistic interaction between proteasome inhibitors and tumor necrosis
      factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising approach to
      induce cell death in tumor cells. However, the molecular and biochemical
      mechanisms of this synergism have been proven to be cell type specific. We
      therefore focused our investigation on TRAIL-resistant colon carcinoma cells in
      this study. DNA fragmentation, mitochondrial membrane depolarization and
      increased caspase-3-like enzyme activity was exclusively induced only by combined
      treatment with proteasome inhibitors (epoxomicin, MG132, bortezomib/PS-341) and
      TRAIL. The expression level of anti-apoptotic proteins (XIAP, survivin, Bcl-2,
      Bcl-XL), regulated by NF-kappaB transcription factor, was not effected by any of
      these treatments. TRAIL alone induced only partial activation of caspase-3 (p20),
      while the combination of TRAIL and proteasome inhibition led to the full
      proteolytic activation of caspase-3 (p17). Only the combination treatment induced
      marked membrane depolarization and the release of cytochrome c, HtrA2/Omi and
      Smac/DIABLO. Apoptosis-inducing factor (AIF) was not released in any of these
      conditions. These results are consistent with a model where the full activation
      of caspase-3 by caspase-8 is dependent on the release of Smac/DIABLO in response
      to the combined treatment. This molecular mechanism, independent of the
      inhibition NF-kappaB activity, may provide rationale for the combination
      treatment of colon carcinomas with proteasome inhibitors and recombinant TRAIL or
      agonistic antibody of TRAIL receptors.

PMID- 16998593
TI  - The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas.
AB  - The current WHO classification of human astrocytomas has limitations in
      predicting prognosis and diagnosis, and there is a need for additional factors.
      Several studies have investigated the clinical value of proliferative activity in
      these tumors, especially the Ki-67/MIB-1 labeling index (LI). The aim of this
      study was to review the literature on this topic to get a survey of the current
      experience. All studies show increasing values of Ki-67/MIB-1 LI with increasing
      grade of malignancy. Most of them demonstrate that MIB-1 LI differentiates well
      between diffuse astrocytomas WHO grade II (AII) and anaplastic astrocytomas (AA)
      and between AII and glioblastomas (GM), but not between AA and GM. There is,
      however, considerable overlap of indices between the different malignancy groups.
      Further, in most studies positive correlations between MIB-1 LI and survival are
      found, though the proposed cut-off values vary substantially between the reports.
      The studies reviewed report MIB-1 LI as an important prognostic factor in human
      astrocytomas. Due to the great spread of values between the various tumor grades,
      however, MIB-1 LI cannot be used as a diagnostic factor alone but should be used
      in combination with established criteria of histological malignancy. It may be
      especially useful in cases where histology reveals a low-grade astrocytoma
      whereas other parameters indicate a more malignant neoplasm. Thus, it is our
      opinion that MIB-1 LI should be a part of the routine investigation in patients
      with astrocytic tumors. Until larger multicenter studies based on standardized
      immunohistopathological procedures have been completed, each laboratory has to
      establish its own practice.

PMID- 16998594
TI  - HER-2/neu genotype of breast cancer may change in bone metastasis.
AB  - The genotype of breast cancer (BRC) is considered to be relatively stable during
      tumor progression, accordingly, determination of the estrogen receptor and HER
      2/neu status is currently based on the primary tumor. However, recent data
      suggest that the gene expression profile of the metastatic lesion can be
      different compared to that of the primary BRC. Accordingly, it is possible that
      the HER-2/neu status is different in the metastatic lesion and the primary BRC.
      Since the bone is the most frequent metastatic site during the progression of
      BRC, we have analyzed the HER-2/neu status of 48 bone metastatic BRC cases by
      immunohistochemistry and fluorescent in situ hybridization, and it was possible
      to compare it to the primary site in 23 cases. The frequency of HER-2/neu
      amplification of BRC in the primary tumors was found to be 17.4% compared to
      10.5% in bone metastases. Half of BRC cases with HER-2/neu amplification lost
      this genotype in bone metastases (4/23 versus 2/23, respectively) and even in the
      2 cases where HER-2/neu amplification was retained in the metastases, the copy
      number was found to be decreased compared to the primary tumor. Based on our data
      and previous reports in the literature, we suggest to perform HER-2/neu testing
      both on primary tumor and samples obtained from BRC metastases, at least in case
      of primary tumors with HER-2/neu amplification, before introduction of HER-2/neu
      targeting therapy.

PMID- 16998595
TI  - Immunohistochemical expression of p16 and p53 in vulvar intraepithelial neoplasia
      and squamous cell carcinoma of the vulva.
AB  - This study was undertaken to examine the expression of p16 and p53 in vulvar
      intraepithelial neoplasia (VIN) and squamous cell carcinoma (SCC) of the vulva.
      We also analyzed the relationship between p16 and p53 immunoexpression in women
      younger vs. older than 55 years of age. Seventyseven histologic samples of vulvar
      tissue, treated surgically between June 2000 and November 2004 at the Complexo
      Hospitalar Santa Casa (Porto Alegre, Brazil), were investigated. We analyzed 28
      cases of VIN, 37 cases of SCC and 12 normal vulvar tissues. The percentage of
      immunohistochemical positivity for p16 had the following distribution across the
      groups: VIN: 21.4% (6/28), cancer: 24.3% (9/37) and control: absent (p=0.202).
      p53 expression showed the following percentages: VIN: 60.7% (17/28), cancer:
      18.9% (7/37) and control: 8.3% (1/12) (p=0.01). p16 expression in the cancer
      group (mean age: 63.4 years) was positive in 6 and 3 cases of women younger or
      older than 55 years, respectively (54.5% vs. 11.5%, p=0.01). p53 expression was
      not detected in young females with cancer, while it was expressed in 7/26 (26.9%)
      cases of the group of females older than 55 years of age (p=0.08). Our results
      suggest an increase in the immunohistochemical expression of p16 protein in young
      women with squamous cell carcinoma of the vulva, and a possible association with
      a low expression of p53.

PMID- 16998596
TI  - Differential regulation of umbilical cord blood and leukemic B cells by
      interferon-alpha (IFN-alpha): observations in cultured cells.
AB  - The exact mechanism of the beneficial therapeutic action of interferon-a (IFN
      alpha) in B-cell-lineage malignancies has not been adequately explained. Here we
      report on the differential effect of IFN-alpha2b on non-malignant B cells of
      umbilical cord blood and leukemic B-cell lines JY, BL-41 and BCBL-1. Leukemic
      cell proliferation was characterized by colony assay, whereas apoptosis was
      investigated by flow cytometry of propidium iodide-stained cells. The degree of
      differentiation was evaluated by measuring the expression level of Fcgamma
      receptor-II (FcgammaRII) labeled with anti-CD32-FITC monoclonal antibody using
      flow cytometry. IFN-alpha protected umbilical cord blood CD19-positive B
      lymphocytes from apoptotic cell death in vitro. IFN-alpha significantly decreased
      colony formation of all three cell lines, and in contrast to normal cells,
      induced apoptosis in JY and BL-41 and excessive necrosis in HHV-8 infected BCBL-1
      cells. FcgammaRII was upregulated both in normal and in leukemic B cells as
      indicated by an increase both in the proportion of CD32-positive cells and the
      mean fluorescence intensity. From our results it seems that antiproliferative,
      apoptotic and differentiative effects of IFN-alpha are interrelated but distinct
      cellular events, which are differentially regulated in normal, leukemic and virus
      infected cells of the B-cell lineage.

PMID- 16998597
TI  - Neuropathological spectrum of pilocytic astrocytoma: an Indian series of 120
      cases.
AB  - Pilocytic astrocytomas (PAs) are generally well circumscribed, slowly growing,
      cystic tumors, occurring in the pediatric age group. Our aims were to
      retrospectively analyze the neuropathological spectrum of PA, and correlate it
      with various clinicopathological features. A total of 120 PAs, diagnosed and
      managed at this center during a 5-year period, were included. The study
      population had a mean age of 18.9 years, with male predominance (68.3%), and
      demonstrated predilection for posterior fossa (61.7%). On histopathology,
      biphasic pattern (89.2%) along with Rosenthal fibers (66.7%) and eosinophilic
      granular bodies (60%) were present in the majority of cases. Vascular features
      were characterized by perivascular hyalinization (51.7%), angiomatous
      proliferation (21.7%) and glomeruloid changes (21.7%). Hemosiderin-laden
      macrophages were noted in 37.1% of cases. Further, 60.8% showed lymphoplasmacytic
      infiltration, while atypia and necrosis were present in 25.8% and 1.7% of cases,
      respectively. Statistical evaluation revealed significant correlation of
      angiomatous proliferation with age (< or =12 and >12-year age groups) (p=0.011);
      and of hemosiderin deposition with angiomatous proliferation (p=0.006),
      perivascular hyalinization (p=0.035), and age (< or =12 and >12-year age groups)
      (p=0.028). This study emphasizes that though PAs generally display classical
      histomorphology, diagnosis may be challenging in patients with unusual
      clinicopathological features, e.g. in older patients, uncommon location, absence
      of biphasic pattern, or presence of nuclear atypia, mitotic figures and necrosis,
      and also in cases of small biopsies. In the absence of diagnostic histology
      enumerated above, vascular features like angiomatous proliferation, glomeruloid
      changes and perivascular hyalinization, along with hemosiderinladen macrophages
      and perivascular lymphocytic infiltration should be considered as surrogate
      histological markers of PA.

PMID- 16998599
TI  - A path or a new road in laboratory diagnostics? Biological mass spectrometry:
      facts and perspectives.
AB  - Proteins in tissues and biofluids and their many attributes define the proteome.
      Proteome can be directly correlated to known diseases and histological regions
      allowing the diagnosis and monitoring of disease progression as well predicting
      the patient's response to specific treatments. Proteomics performs large-scale,
      high-throughput characterization of the human proteome, among others by
      biological mass spectrometry. Proteinchip technology coupled with bioinformatics
      is able to screen any protein source for putative disease biomarkers from a small
      sample volume (microliter range) by surface-enhanced laser desorption/ionization
      time-of-flight mass spectrometry (SELDI-TOF MS). This article discusses on a
      basic level both the technology and reliability of these methods.

PMID- 16998598
TI  - Human papilloma virus and p53 expression in bladder cancer in Egypt: relationship
      to schistosomiasis and clinicopathologic factors.
AB  - The aim of the current study was to compare the role of p53 and human
      papillomavirus (HPV) in schistosomiasis-related and schistosomiasis-unrelated
      carcinoma of the urinary bladder. To achieve this aim, we investigated 114
      bladder carcinomas for p53 oncoprotein expression by immunohistochemistry and for
      human papillomavirus by in situ hybridization technique. The results revealed
      that 64 tumors (56.1%) were schistosomiasis-associated. Sixty seven (58.8%) were
      transitional cell carcinomas and 32 (28%) were squamous cell carcinomas. The
      remaining 15 tumors (13.2%) included adenocarcinomas and sarcomatoid carcinomas.
      In both schistosomiasis-associated and non-associated carcinomas, p53 oncoprotein
      expression was significantly higher in poorly differentiated tumors. However, it
      was significantly higher in locally more invasive tumors in the schistosomal
      carcinomas only. HPV types 16/18 could be detected in 1 of the 114 bladder
      carcinomas (0.95%), which was schistosomiasis-related squamous cell carcinoma in
      situ. These results suggest that p53 immunohistochemistry can be a prognostic
      factor in both schistosomal and nonschistosomal bladder cancer. More importantly,
      HPV does not seem to play a role in the pathogenesis of either type of bladder
      cancer in our country.

PMID- 16998600
TI  - Post-menopausal bleeding: a rare presentation of metastatic uveal melanoma.
AB  - Uveal melanoma differs from cutaneous melanoma in many ways, including its
      pattern of metastasis, and exhibits latency with clinical evidence of metastasis
      sometimes appearing many years after primary diagnosis. Most patients develop
      metastasis within the liver, but some may present with metastasis to other sites.
      We report a case of uveal melanoma that presented with post-menopausal bleeding
      due to metastasis. Further investigation revealed widespread metastatic disease
      and the patient was not fit for chemotherapy. She died two months after
      presentation: autopsy revealed metastases in many sites, including the uterus,
      right ovarian fibroma, kidney, mesentery, liver, lung, thyroid, bone marrow and
      skin. The immediate cause of death was cardiac tamponade due to a malignant
      effusion secondary to cardiac metastasis. This case illustrates the widespread
      metastatic potential of uveal melanoma and highlights the potential for unusual
      presentation of metastatic disease from this eye tumor.

PMID- 16998601
TI  - Infiltrating ductal carcinoma of the breast, metastatic to axillary lymph nodes
      harboring primary tuberculous lymphadenitis.
AB  - A 46-year-old female presented with lump in the left breast. Fine-needle
      aspiration cytology (FNAC) from breast and axillary lymph node revealed
      infiltrating ductal carcinoma with metastasis in axillary node. The patient
      underwent radical mastectomy with axillary lymph node dissection.
      Histopathological examination showed concomitant presence of metastatic tumor
      deposits and tubercular lymphadenitis in 8/18 nodes. The case is presented for
      its rarity and illustrates that FNAC can fail to detect mixed lesions unless
      multiple punctures from many sites are performed.

PMID- 16998603
TI  - Human empathy through the lens of social neuroscience.
AB  - Empathy is the ability to experience and understand what others feel without
      confusion between oneself and others. Knowing what someone else is feeling plays
      a fundamental role in interpersonal interactions. In this paper, we articulate
      evidence from social psychology and cognitive neuroscience, and argue that
      empathy involves both emotion sharing (bottom-up information processing) and
      executive control to regulate and modulate this experience (top-down information
      processing), underpinned by specific and interacting neural systems. Furthermore,
      awareness of a distinction between the experiences of the self and others
      constitutes a crucial aspect of empathy. We discuss data from recent behavioral
      and functional neuroimaging studies with an emphasis on the perception of pain in
      others, and highlight the role of different neural mechanisms that underpin the
      experience of empathy, including emotion sharing, perspective taking, and emotion
      regulation.

PMID- 16998604
TI  - Fmr1 KO mice as a possible model of autistic features.
AB  - Autism is a pervasive developmental disorder appearing before the age of 3, where
      communication and social interactions are impaired. It also entails stereotypic
      behavior or restricted interests. Although this disorder was first described in
      1943, little is still known about its etiology and that of related developmental
      disorders. Work with human patients has provided many data on neuropathological
      and cognitive symptoms, but our understanding of the functional defects at the
      cellular level and how they come about remains sketchy. To improve this
      situation, autism research is in need of valid animal models. However, despite a
      strong hereditary component, attempts to identify genes have generally failed,
      suggesting that many different genes are involved. As a high proportion of
      patients suffering from the Fragile X Syndrome show many autistic symptoms, a
      mouse model of this disorder could potentially also serve as a model for autism.
      The Fmr1 KO mouse is a valid model of the Fragile X Syndrome and many data on
      behavioral and sensory-motor characteristics of this model have been gathered. We
      present here an assessment of autistic features in this candidate model. We
      conclude that Fmr1 KO mice display several autistic-like features, but more work
      is needed to validate this model.

PMID- 16998605
TI  - Atopic dermatitis. A clinical challenge.
AB  - Atopic dermatitis has a significant impact on both the pediatric and adult
      population worldwide, which has triggered extensive research on the topic.
      However, various limitations have created difficulties both in making accurate
      diagnoses and effectively managing atopic dermatitis patients. This review
      summarizes the current knowledge in the field, providing an overview of the
      pathophysiology, disease progression, clinical presentation, and diagnosis and
      treatment of atopic dermatitis.

PMID- 16998606
TI  - Genetic susceptibility to environmental carcinogenesis in Slovenian melanoma
      patients.
AB  - The skin acts as the first defence barrier against external environmental
      pollutants, including chemicals and UV radiation. Cytochrome P450 CYP1A1 and
      glutathione S-transferases (GSTs) found in melanocytes and skin basal layers were
      shown to participate both in the metabolism of xenobiotics and in detoxification
      of reactive oxygen species (ROS). In our study we analysed the distribution of
      single and combined CYP1A1, GSTM1, GSTT1 and GSTP1 genotypes contributing to
      inter-individual differences in metabolism of xenobiotics and ROS in 125
      Slovenian healthy individuals and in 140 patients with sporadic malignant
      melanoma. Our results showed no statistically significant differences between
      melanoma patients and healthy controls in the frequency of polymorphic CYP1A1 and
      GST genotypes. The risk of developing melanoma was not significantly increased in
      individuals homo- or heterozygous for the CYP1A1*2A allele combined with GSTM1*0
      genotype (OR: 1.86; 95% CI: 0.36-7.71), but increased slightly in carriers of
      CYP1A1*2A combined with both GSTM1*0 and GSTT1*0 genotypes (OR: 3.42; 95% CI:
      0.36-29.6). Our results indicate that factors other than the polymorphic genes
      coding xenobiotic metabolising enzymes play a major role in protection against
      environmental carcinogenesis in human skin.

PMID- 16998607
TI  - Cutaneous Langerhans cell histiocytosis with subsequent development of
      haematological malignancies. Report of two cases.
AB  - Adult cutaneous Langerhans cell histiocytosis (LCH) is a rare disease. We report
      two cases illustrating the variability of the clinical presentation and the
      response to treatment. In both cases a remission was achieved: in one case a
      partial remission with psoralen plus UVA irradiation (PUVA) and methotrexate plus
      topical corticosteroid ointment; in the other case by treatment with thalidomide.
      Despite a therapeutic response, both patients later developed haematological
      malignancies: a chronic myelo-monocytic leukaemia and an acute lymphatic
      leukaemia. In conclusion, patients with adult cutaneous LCH should be monitored
      carefully so that a secondary malignancy is not overlooked.

PMID- 16998608
TI  - Branchial cysts. A report of 4 cases.
AB  - OBJECTIVE: Cysts presented in the lateral aspect of the neck are relatively
      uncommon anomalies. Many theories have been proposed to explain the aetiology of
      these cysts, grouped in two main categories: the congenital and the cervical
      lymph nodes cystic transformation hypotheses. SETTINGS: In this paper we present
      4 patient-cases documented in the department of Maxillofacial Surgery, and try to
      trace the profile of these lesions and investigate their origin. RESULTS: All
      lesions were well circumscribed by Computed Tomography, and prior to surgery they
      were assessed by means of fine needle aspiration cytology. Neutrophils, debris
      and mature squamous epithelial cells including degenerate forms, were the key
      features in the cytological diagnosis. Histologic examination of the excised
      surgical specimen established the diagnosis in all cases. CONCLUSIONS: Our
      findings, compatible with the congenital theory lead us to the conclusion that
      the branchial cysts are the result of imperfect obliteration of the branchial
      clefts, arches, and pouches.

PMID- 16998610
TI  - Zosteriform lichen planus-like eruption.
AB  - Lichen planus (LP) is a relatively common papulosquamous skin disease of unknown
      etiology, it is believed to be a T-cell mediated disorder. In addition to the
      cutaneous eruptions it may also affect mucous membranes, nails or cause scarring
      alopecia. Lichen planus appears in various clinical variants which are
      categorized according to the morphology and configuration of lesions. We present
      a 34-year-old man who developed a papular eruption localized unilaterally on the
      right side of the body in a linear-zosteriform pattern within the L5-S1 nerve
      segments. The skin lesions clinically and histologically mimicked LP. Topical
      treatment with betamethason ointment for one month led to remarkable improvement,
      but a zosteriform hiperpigmentation persisted. According to the clinical findings
      in our patient and a review of the literature, we believe that
      lichenoidzosteriform eruption is a variant of lichen planus or a herpes zoster
      infection.

PMID- 16998609
TI  - Rothmund-Thomson syndrome. The first case with plantar keratoderma and the second
      with coeliac disease.
AB  - We report two unusual patients with Rothmund-Thomson syndrome (RTS), a rare
      genodermatosis. The first patient is a 5-year-old girl with congenital
      poikiloderma, photosensitivity, plantar punctate keratoderma, stunted growth and
      severe mental retardation. Plantar keratoderma associated with RTS has been
      reported only once. The second patient is a 21-year-old female presenting with
      rounded "moon" face, trunk obesity, coeliac disease, short stature and mild
      mental retardation. This is the first case of RTS associated with coeliac
      disease.

PMID- 16998611
TI  - Probable cutaneous allergic response to subcutaneous heparin--a case report.
AB  - Heparin is a heterogeneous mixture of sulfated mucopolysaccharides, commonly used
      injectable anticoagulant. It is known to cause cutaneous adverse reactions like
      eczema, erythematous plaques, exfoliative dermatitis and tissue necrosis. We
      report a case of probable cutaneous allergic response caused by injection of
      heparin with an established causality and severity. The reaction developed after
      stopping the drug therapy and after the patient had already been discharged.
      Since heparin is a widely used drug and this reaction can manifest even after the
      drug therapy has ceased, thorough counseling of the patient is mandatory.

PMID- 16998612
TI  - Biofilms, a new approach to the microbiology of dental plaque.
AB  - Dental plaque has the properties of a biofilm, similar to other biofilms found in
      the body and the environment. Modern molecular biological techniques have
      identified about 1000 different bacterial species in the dental biofilm, twice as
      many as can be cultured. Oral biofilms are very heterogeneous in structure. Dense
      mushroom-like structures originate from the enamel surface, interspersed with
      bacteria-free channels used as diffusion pathways. The channels are probably
      filled with an extracellular polysaccharide (EPS) matrix produced by the
      bacteria. Bacteria in biofilms communicate through signaling molecules, and use
      this "quorum-sensing" system to optimize their virulence factors and survival.
      Bacteria in a biofilm have a physiology different from that of planktonic cells.
      They generally live under nutrient limitation and often in a dormant state. Such
      "sleepy" bacteria respond differently to antibiotics and antimicrobials, because
      these agents were generally selected in experiments with metabolically active
      bacteria. This is one of the explanations as to why antibiotics and
      antimicrobials are not as successful in the clinic as could be expected from
      laboratory studies. In addition, it has been found that many therapeutic agents
      bind to the biofilm EPS matrix before they even reach the bacteria, and are
      thereby inactivated. Taken together, these fundings highlight why the study of
      bacteria in the oral cavity is now taken on by studying the biofilms rather than
      individual species.

PMID- 16998613
TI  - Periodontal disease and systemic conditions: a bidirectional relationship.
AB  - For decades, physicians and dentists have paid close attention to their own
      respective fields, specializing in medicine pertaining to the body and the oral
      cavity, respectively. However, recent findings have strongly suggested that oral
      health may be indicative of systemic health. Currently, this gap between
      allopathic medicine and dental medicine is quickly closing, due to significant
      findings supporting the association between periodontal disease and systemic
      conditions such as cardiovascular disease, type 2 diabetes mellitus, adverse
      pregnancy outcomes, and osteoporosis. Significant effort has brought numerous
      advances in revealing the etiological and pathological links between this chronic
      inflammatory dental disease and these other conditions. Therefore, there is
      reason to hope that the strong evidence from these studies may guide researchers
      towards greatly improved treatment of periodontal infection that would also
      ameliorate these systemic illnesses. Hence, researchers must continue not only to
      uncover more information about the correlations between periodontal and systemic
      diseases but also to focus on positive associations that may result from treating
      periodontal disease as a means of ameliorating systemic diseases.

PMID- 16998614
TI  - N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists suppress the
      superior sagittal sinus-evoked activity of C1 spinal neurons responding to tooth
      pulp electrical stimulation in rats.
AB  - The aim of the present study was to determine whether there is a convergence of
      inputs from tooth pulp (TP) and the superior sagittal sinus (SSS) on rat C1
      spinal neurons, and to examine the effects of iontophoretically applied N-methyl
      D: -aspartate (NMDA) and non-NMDA receptor antagonists on the SSS-evoked activity
      of C1 neurons. Extracellular single unit-recordings were made from 20 C1 units
      responding to TP electrical stimulation with a constant temporal relationship to
      a digastric electromyogram signal, using a multibarrel electrode in pentobarbital
      anesthetized rats. Ninety percent of C1 neurons (18/20) responding to TP
      stimulation also responded to the SSS stimulation. These neurons were considered
      to be SSS-afferent inputs from Adelta-fibers (5.8 +/- 0.6 m/s; n = 18), based on
      the calculation of nerve conduction velocity. After the iontophoretic application
      (30, 50, and 70 nA) of an NMDA receptor blocker (5R-10S)-(+)-5-methyl-10,11
      dihydro-5H-dibenzo[a,d] cycloheptene-5,10-imine hydrogen maleate (MK801) or a non
      NMDA receptor blocker (6-cyano-7-nitroquinoxaline-2,3-dione) (CNQX), the mean
      number of spikes responding to the SSS stimulation significantly decreased (30,
      50, and 70 nA; P < 0.05). These results suggest that there is a convergence of
      inputs from SSS and TP afferents on C1 neurons; it is possible that both NMDA and
      non-NMDA receptors located on C1 neurons may be targets for the treatment of the
      trigeminal referred pain associated with migraine.

PMID- 16998615
TI  - Repeated androgen and thyroid hormone injection modulates the morphology of
      hormone-responsive duct cells in the mouse parotid gland.
AB  - When the parotid glands of normal male and female ICR mice (12 weeks of age) were
      examined under a light microscope, no granular cells were seen in the duct
      system. However, transmission electron microscopy revealed that, in both sexes,
      many striated duct cells contained a few electron-dense secretory granules in
      their subluminal cytoplasm and had formed so-called granular striated tubules
      (GSTs) in some of the striated duct segments. These secretory granules were not
      large enough to be visible with a light microscope. Fully fledged granular cells,
      containing large secretory granules visible with a light microscope, could be
      induced in the GST segments of the glands of males by injection with 5alpha
      dihydrotestosterone (DHT), triiodothyronine (T(3)), and dexamethasone (Dex),
      given alone or in combination every other day for 2 weeks. Dex alone showed no
      effect on the GSTs in this study. Both DHT and T(3), either individually or with
      Dex, were moderately effective, inducing a few scattered fully fledged granular
      cells. A stronger effect was detected after concomitant injection of DHT and
      T(3), with or without Dex, with more abundant fully developed granular cells
      appearing in the GST segments. Electron microscopy revealed that these granular
      cells had abundant large secretory granules in their apical two-thirds, a basal
      nucleus, and modest basal infoldings. By contrast, the effect of the same
      hormones was very weak in the glands of females, and even the concomitant
      injection of DHT and T(3), with or without Dex, rarely induced fully fledged
      granular cells. These results indicate a close similarity between the ductal
      systems of the major salivary glands of the mouse, in terms of some of the
      striated duct segments containing secretory granules, being under the same
      multihormonal regulation, and being sexually dimorphic.

PMID- 16998616
TI  - Decreased response of osteoblasts obtained from aged Cohen diabetic sensitive
      rats to sex steroid hormones and 1,25OH2D3 in culture.
AB  - Patients with diabetes mellitus are known to develop osteopenia and osteoporosis,
      apparently as a reduction in the process of bone formation. In order to evaluate
      whether bone-modulating hormones--estradiol, testosterone, and 1,25(OH)(2)D(3)-
      have different effects on osteoblasts derived from diabetic and from normal non
      diabetic rats, we studied the specific effects of these hormones on the
      differentiation and function of cultured osteoblasts derived from 1-year-old
      Cohen diabetic rats. (The Cohen diabetic model consists of a diabetic-sensitive
      strain [CDs; diabetic] and a diabetic-resistant strain [CDr; normal]). The CDs
      and CDr male and female rats were fed on a regular diet (RD) or a high-sucrose
      low-copper diet (HSD; diabetogenic). On the HSD diet, only CD rats develop type 2
      diabetes, while CDr do not. Bones were removed for primary osteoblast cultures,
      and osteoblastic responses to the bone-modulation hormones--estradiol,
      testosterone, and 1,25(OH)(2)D(3)--were studied. In male rats fed RD, primary
      cultures of osteoblasts without hormone addition to the culture medium showed
      that alkaline phosphatase (ALP) activity was similar in the Cohen diabetic rats
      (both CDr and CDs) to that of the original Sabra strain. However, collagen
      synthesis was reduced in the CDr and CDs compared to the Sabra strain. The
      addition of the hormones to the culture medium did not change ALP activity or
      collagen synthesis in the male-derived osteoblasts, but increased mineralization
      in all strains. In female rats (studied only in CDs and CDr animals) there were
      no differences between animals fed the RD. HSD increased the basal activity of
      ALP in the CDr but not in the CDs rats, and decreased the rate of collagen
      synthesis in both CDr and CDs (diabetic) animals. The addition of the bone
      modulation hormones to the culture medium further increased ALP activity in the
      osteoblasts derived from the CDr animals, while decreasing ALP activity in the
      CDs. These hormones also decreased collagen synthesis in both strains and
      increased mineralization in all osteoblasts. In conclusion, the metabolic status
      (HSD and diabetes) in rats prior to culture affected the phenotype of cultured
      osteoblasts, decreasing their response to bone-modulation hormones. This
      decreased response, especially to estradiol, may be a major cause of the
      osteopenia observed in diabetes.

PMID- 16998617
TI  - In vitro chromosome aberration tests using human dental pulp cells to detect the
      carcinogenic potential of chemical agents.
AB  - To examine if human dental pulp cells are useful for assessing the carcinogenic
      potential of chemical agents, we cultured human dental pulp cells from adults and
      studied the ability of chemical agents known to be carcinogenic to induce
      chromosome aberrations in these cells. We confirmed that human dental pulp cells
      in primary or secondary cultures had the capability of accumulating calcium in
      vitro as detected by Alizarin red staining and generating dentin-like tissue in
      immunocompromised mice. These phenotypes were maintained even in cells at seven
      passages. Next, we examined if chromosome aberrations were induced by exposure of
      human dental pulp cells (designated here as D824 cells) at seven to nine passages
      to chemical agents with carcinogenic activity. Statistically significant
      increases in the frequencies of chromosome aberrations were induced in D824 cells
      treated with a direct-acting carcinogen, mitomycin C, for 3 h. Chromosome
      aberrations were also induced at statistically significant levels in D824 cells
      treated with an indirect-acting carcinogen, cyclophosphamide, for 2 h in the
      presence of exogenous metabolic activation with rat liver postmitochondrial
      supernatant. Cyclophosphamide failed to induce chromosome aberrations in the
      absence of exogenous metabolic activation. Although the reliability of chromosome
      aberration tests using human dental pulp cells remains to be validated by
      studying the ability of various other chemical agents with or without
      carcinogenic activity to induce chromosome aberrations, this chromosome
      aberration test system may be useful for carcinogenic risk assessment in the
      target cells.

PMID- 16998618
TI  - Cephalometric evaluation of anterior open-bite nonextraction treatment, using
      multiloop edgewise archwire therapy.
AB  - There are very few reports of extensive and detailed cephalometric investigations
      of nonextraction treatment changes for patients with anterior open bite. The
      purpose of this study was to evaluate changes in dentomaxillofacial morphology by
      way of lateral and oblique cephalograms of patients who had undergone multiloop
      edgewise archwire (MEAW) therapy for anterior open-bite correction. The subjects
      consisted of 21 Japanese female patients who received MEAW therapy without
      premolar extraction. The mean pre- and posttreatment ages were 16 years 9 months
      and 19 years, respectively. Lateral and oblique cephalograms were taken before
      and after treatment. Fifteen angular and 29 linear measurements were obtained
      from the lateral cephalograms; 17 angular and 20 linear measurements were
      obtained from the oblique cephalograms. Treatment changes were evaluated by the
      paired t-test. The upward and forward rotational changes of the mandible
      consequent to the use of the MEAWs and anterior vertical elastics were larger
      than the downward and backward rotational changes of the mandible, due to the
      extrusion of the posterior teeth by leveling and alignment. The uprighting and
      retrusion of the premolars and molars, and the extrusion, uprighting, and/or
      retrusion of the incisors and canines played important roles in the anterior open
      bite nonextraction treatment by dint of the MEAW technique.

PMID- 16998619
TI  - Ibuprofen as a pre-emptive analgesic is as effective as rofecoxib for mandibular
      third molar surgery.
AB  - The objective of this study was to compare the pre-emptive analgesic effect of
      rofecoxib, a cyclooxygenase (COX)-2 inhibitor, with a more traditional and
      commonly used analgesic, ibuprofen, for mandibular third molar surgery, utilizing
      a prospective, randomized, double-blind, placebo-controlled clinical trial. Fifty
      five healthy patients who were scheduled to undergo surgical removal of an
      impacted mandibular third molar as outpatients at one of two government dental
      clinics in Fiji were enrolled. The patients were divided randomly into three
      groups to receive 50 mg rofecoxib or 400 mg ibuprofen, or a placebo 1 h prior to
      surgery. A dose of 1000 mg paracetamol was offered as rescue medication.
      Participants recorded their pain intensity on a 10-cm visual analogue scale 1 h
      before and just prior to surgery and every 30 min for 6 h following surgery.
      There were no significant analgesic differences between rofecoxib and ibuprofen
      at any time intervals postoperatively. Ibuprofen was significantly better at
      reducing pain at all time intervals by comparison with the placebo. Rofecoxib
      provided significantly better pain relief compared with the placebo, except at
      60, 180, and 240 min postoperatively. Rescue medication use was significantly
      lower in the rofecoxib and ibuprofen groups by comparison with the placebo group;
      however, there was no significant difference between the two therapeutic groups.
      Rescue medication was used by 50%, 25%, and 94% of patients receiving rofecoxib,
      ibuprofen, and placebo, respectively. Ibuprofen, a commonly used over-the-counter
      analgesic, is as effective as rofecoxib for the relief of acute postoperative
      pain following third molar surgery when used pre-emptively.

PMID- 16998620
TI  - Expression of keratin 18 in the periderm cells of the lingual epithelium of fetal
      rats: visualization by fluorescence immunohistochemistry and differential
      interference contrast microscopy.
AB  - We examined the expression of keratin 18 (K18), by immunofluorescence staining,
      while monitoring morphological changes in the periderm on the lingual epithelium
      of rats by laser-scanning microscopy of epoxy resin-embedded, semi-ultrathin
      sections. We also examined differential interference contrast (DIC) images of the
      same sections to define the histology and morphology of the cells. It is
      difficult to visualize histological details of the fetal lingual epithelium of
      the rat on semi-ultrathin sections by light microscopy after immunohistochemical
      staining, because the histological structures in such sections cannot be
      distinguished by standard counterstaining. To solve this problem and to visualize
      keratin 18 (K18), we used a combination of immunofluorescence staining of semi
      ultrathin sections and corresponding differential contrast (DIC) images, obtained
      by laser-scanning microscopy.

PMID- 16998621
TI  - Molecular biology of hepatitis B virus: effect of nucleotide substitutions on the
      clinical features of chronic hepatitis B.
AB  - Hepatitis B virus (HBV) is a major cause of liver disease worldwide. It is
      covered with envelope (surface antigen) proteins with the nucleocapsid (core
      antigen) inside. In the nucleocapsid, there is an incomplete double-stranded DNA
      and a DNA polymerase. Four genes, S, C, X, and P, are encoded, and these
      partially overlap. Mutations have been reported in each gene and in their
      promoter regions, and these mutations can change the efficiency of HBV
      replication and the clinical course of patients. In this article, we review the
      relationship between the molecular biology of HBV and its clinical outcome.

PMID- 16998622
TI  - Compound overload of copper and iron in patients with Wilson's disease.
AB  - This review of the copper-iron interaction in Wilson's disease was mainly based
      on ten patients (three females and seven males) studied in our institutes because
      the genetic tests of ATP7B for Wilson's disease of primary copper toxicosis and
      HFE for hemochromatosis, the biochemical parameters of copper and iron, and
      morphological studies on biopsied liver specimens were complete. All patients had
      hypoceruloplasminemia and hepatic lesions compatible with Wilson's disease. One
      patient was homozygous and nine patients were compound heterozygous for the
      mutations in ATP7B, and all patients were free from the major mutation, C282Y, of
      HFE. The biochemical parameters of iron metabolism were not specific, except for
      serum ferritin concentration. Judging from the traditional criteria, seven
      patients had hyperferritinemia. Histochemical iron was stained in the livers of
      seven patients and histochemical copper was found in nine patients. Microanalysis
      was more sensitive than histochemistry, detecting copper and iron accumulation in
      the hepatocellular lipofuscin particles of all patients. Using an improved
      fixative, intralipofuscin distribution was found to be different between
      cuprothionein and iron complexes. Iron overload in Wilson's disease might be
      worsened after treatment because of the close relation to hypoceruloplasminemia,
      in which the iron efflux from the liver to the circulation is disturbed.

PMID- 16998623
TI  - The role of electron microscopy in the diagnosis of surgical pathology in the
      central nervous system.
AB  - Electron microscopy has played an important role in the diagnosis of surgical
      pathology and the establishment of new tumor entities and variants in the central
      nervous system. However, the use of ultrastructural analysis of brain tumors has
      decreased with the advent of immunohistochemistry. I present here my personal
      experiences and perspective on the role of electron microscopy in surgical
      neuropathology.

PMID- 16998624
TI  - The ultrastructural morphology of native hepatitis B virus.
AB  - Cell lines (2.2.15 cells) capable of supporting the replication of hepatitis B
      virus (HBV) DNA and intact viral particles have been established by HBV DNA
      transfection into HepG2 cells. The purpose of this study was to determine the
      ultrastructural morphology of native HBV particles without purification in the
      culture supernatants and in sera from patients. Electron microscopy (EM) and
      immunogold EM of the samples were carried out using polyclonal and monoclonal
      anti-hepatitis B surface antigen antibodies. HBV particles in the purified
      samples from the culture supernatants by density-gradient centrifugation were
      examined to compare the morphology with that of unpurified samples. EM and
      immunogold EM studies demonstrated the presence of Dane particles (41.8 nm in
      diameter), cobra-shaped (head diameter, 42.4 nm), and horn-shaped (head diameter,
      43.5 nm) particles in the culture supernatants and in the sera from two patients.
      The tail of the cobra-like particles had a diameter of 21.0 nm and a length of
      214 nm. The hornlike particles had a long branch 20.1 nm in diameter with a
      length of 189 nm, and a short branch 21.4 nm in diameter with a length of 112 nm.
      The ratio of Dane particles and cobra- and horn-shaped particles in the
      supernatants was 5 : 4 : 1. After ultracentrifugation, the cobra- and horn-shaped
      particles completely disappeared; there were only Dane particles together with
      spheres of 22 nm and filaments. In conclusion, this study showed for the first
      time that the native replicative form of HBV is cobra- and horn-shaped.

PMID- 16998625
TI  - Immunohistochemical and electron-microscopic observation of beta-cells in
      pancreatic islets of spontaneously diabetic Goto-Kakizaki rats.
AB  - The Goto-Kakizaki (GK) rat offers a genetic model of type 2 diabetes and displays
      profoundly defective insulin secretion leading to basal hyperglycemia. This
      animal is widely used for studying type 2 diabetes. However, the morphological
      characteristics of the pancreatic islets of Langerhans in GK rats are not fully
      understood. The present study sought to clarify this issue using
      immunohistochemical and electron microscopic techniques. GK rats were killed at
      7, 14, 21, and 35 weeks of age. Structural islet changes were not observed at 7
      weeks old. At 14 and 21 weeks of age, GK rats displayed histopathological islet
      changes. The general shape of islets became irregular, and immunoreaction of beta
      cells against antiinsulin appeared diffusely weakened. Electron microscopy
      revealed that the numbers of so-called beta-granules decreased and the numbers of
      immature granules increased. The Golgi apparatus of beta-cells was developed and
      the cisternae of rough endoplasmic reticulum were often dilated, indicating
      hyperfunction of the cells. However, at 35 weeks old, immunoreactivities of
      dispersed beta-cells into the exocrine portion recovered, and numbers of
      secretory granules increased again and features of the cell organelles did not
      display hyperfunction. These results suggest that insulin deficiency in GK rats
      is not caused by simple dysfunction and/or degeneration of beta-cells but rather
      by more complicated events within cells.

PMID- 16998626
TI  - Expression of FAK-related non-kinase (FRNK) coincides with morphological change
      in the early stage of cell adhesion.
AB  - Focal adhesion kinase (FAK), a protein tyrosine kinase, has recently been
      suggested to play a role in signal transduction through integrins. In fact, FAK
      is involved in cell proliferation and cell motility by performing signal
      transduction through integrins. FAK-related non-kinase (FRNK) has been found to
      be an inhibitor of FAK. As the expression level of FRNK in the cell is very low,
      the study of FRNK has been preferentially performed by gene overexpression, up to
      the present, and the role of constitutive FRNK in cells remains unclear. We
      hypothesized that FRNK is involved in the adhesion of cells to the extracellular
      matrix (ECM) and investigated the expression of FRNK by time kinetic analysis
      shortly after cell seeding. We found that FRNK expression was significantly
      increased in the cells during the early stage of cell adhesion to the ECM. These
      data indicated that FRNK plays an important role in cell adhesion during the very
      early stages of cell culture.

PMID- 16998627
TI  - Myofibroblasts in the stroma of metastatic pulmonary calcification in a patient
      with chronic renal failure.
AB  - We present a case of metastatic pulmonary calcification. Histologically,
      deposition of hematoxyphilic materials was seen along the alveolar and vessel
      walls. Fibrous tissues were also seen within the alveolar lumens, resulting in
      intra-alveolar fibrous pneumonia. Immunohistochemically, CD34-positive
      perivascular adventitial fibroblasts were seen in normal alveolar septa, whereas
      no myofibroblasts were observed. In contrast, perivascular adventitial
      fibroblasts were absent in the alveolar septa of the lesion of metastatic
      calcification, whereas many myofibroblasts were present in the fibrous tissue
      within alveolar lumens. No positive cells for TGF-(beta1) were observed in the
      lesion of metastatic calcification, but positive cells for PDGF-BB were focally
      seen in adveolar epithelial cells. Finally, many myofibroblasts appear in the
      alveolar lumens of metastatic pulmonary calcification, and we suggest that these
      myofibroblasts may be derived from CD34-positive perivascular adventitial
      fibroblasts and PDGF-BB may be involved in the pathogenesis of surrounding
      fibrosis.

PMID- 16998628
TI  - Immunohistochemical and ultrastructural investigation on cutaneous neuroendocrine
      carcinoma: report of a case and review of the literature.
AB  - We report a tumor in an 80-year-old man that was difficult to distinguish from
      other tumors, i.e., small cell carcinoma of the lung, PNET/Ewing tumor, malignant
      lymphoma, or malignant melanoma (amelanotic), and which was finally identified as
      cutaneous neuroendocrine carcinoma using immunohistochemical and ultrastructural
      methods. Autopsy did not show any tumors in the lungs, excluding the possibility
      of small cell carcinoma of the lung. Immunohistochemistry tests gave negative
      results for LCA, UCHL-1, CD3, and CD20, thereby excluding malignant lymphoma, and
      the negative results for S-100 protein and HMB-45 ruled out malignant melanoma.
      The possibility of PNET/Ewing sarcoma was also excluded because of negativity for
      CD99. In addition, the ultramicrostructure showed intercellular junctional
      complexes and neuroendocrine granules, indicating that the tumor had
      characteristics of both epithelial and neuroendocrine tissues. We therefore
      diagnosed the primary carcinoma of the skin as cutaneous neuroendocrine
      carcinoma.

PMID- 16998629
TI  - Comparative cytotoxicity of alachlor on RTG-2 trout and SH-SY5Y human cells.
AB  - The cytotoxic effects of the herbicide alachlor were compared on rainbow trout
      gonadal RTG-2 and human neuroblastoma SH-SY5Y cell lines. The end points
      evaluated in both cells after 24, 48, and 72 h of exposure were total protein
      content (PC), lysosomal function, and mitochondrial's integrity by mitochondrial
      succinate dehydrogenase (SDH) activity. After 24 h, cytoplasmic membrane
      integrity by cytosolic lactate dehydrogenase (LDH) leakage and LDH intracellular
      activity were also studied. In addition, acetylcholinesterase activity (AChE) was
      quantified in SH-SY5Y cells. The possible biotransformation of alachlor by RTG-2
      cells was investigated by analyzing the exposure culture medium by liquid
      chromatography-mass spectrometry. In RTG-2, EC50 values on PC, lysosomal
      function, and SDH activity after 24 h exposure ranged from 80 to 95 microM and
      decreased to approximately 40 microM for longer exposure time periods. SH-SY5Y
      cells were slightly more sensitive than RTG-2 cells, with EC50 values on PC and
      lysosomal function ranging from 87 to 75 microM at 24 h and decreasing to 47
      microM and 34 microM at 72 h, respectively. AChE activity was increased, being
      the most sensitive marker for SH-SY5Y with an EC50 of 20 microM at 24 h. The
      metabolic enzyme SDH was stimulated in SH-SY5Y and reduced in RTG-2 cells. At the
      studied conditions, no metabolites of alachlor were detected in RTG-2 cultures.
      In conclusion, the proposed battery approach is an effective screening tool for
      the safety assessment of environmental contaminants as a complement to fish and
      animal toxicity procedures.

PMID- 16998630
TI  - Growth stimulation and inhibition effects of 4-hydroxybenzoic acid and some
      related compounds on the freshwater green alga Pseudokirchneriella subcapitata.
AB  - 4-hydroxybenzoic acid (4-HBA) exhibited low algal toxicity with the 72-h median
      inhibition concentration (IC50) of 9.9 mmol/L in the standard growth inhibition
      test using the freshwater green alga Pseudokirchneriella subcapitata. In
      contrast, it stimulated the algal growth at lower concentrations ranging from 0.1
      to 1.0 mmol/L. Comparative studies with benzoic acid and 2- and 3-hydroxybenzoic
      acids (2-HBA and 3-HBA) indicated that 2-HBA was the most toxic, giving a 72-h
      IC50 of 0.172 mmol/L, and 4-HBA was the least toxic and that only 4-HBA had the
      pronounced growth stimulation activity. In a semicontinuous exposure to 4-HBA
      (0.15 and 0.3 mmol/L), algae maintained increased cell growth compared with
      controls during up to 10 times consecutive batch cultures, without any indication
      of adaptive responses to the growth enhancing effect of 4-HBA. Return to the
      clean standard medium of the exposed cells resulted in the quick recovery from
      the stimulant effect. Furthermore, 4-HBA (0.3 mmol/L) was found to diminish the
      toxicity of 2-HBA (<1.0 mmol/L). The presence of such compounds in the complex
      mixture might interact with other toxicants to alter the whole toxicity when
      assessed by the algal growth inhibition test. The effects of 4-HBA on P.
      subcapitata growth observed in the present study are not expected for planktonic
      algae in the aquatic environments, because known environmental concentrations are
      far below the effective concentration range.

PMID- 16998631
TI  - Concentration and emission sources of airborne metals in particulate matter in
      the industrial district of Medio Paraiba, state of Rio de Janeiro, Brazil.
AB  - Total suspended particles and 12 airborne metals were determined in 4 sampling
      sites in the industrial region of Medio Paraiba, Brazil. The geometrical means
      for the four sampling locals were (in units of microg/m3): 65.9 in Barra Mansa,
      57.3 in Jardim Paraiba (Volta Redonda), 41.7 in Resende, and 48.9 in Volta Grande
      (Volta Redonda). These values are lower than levels previously determined in
      urban and industrial locals of the Metropolitan Area of Rio de Janeiro. For
      metals, the higher concentrations were obtained for Ca, Zn, Al, Fe, and Mg. Ca,
      Zn, and Al levels are higher than those determined in other industrial areas.
      These three metals are used in steel manufacturing, the main economical activity
      of the region. Enrichment factors for Zn, Cu, Cd, and Pb are higher than 10,
      suggesting an industrial input. Statistical analysis show a high correlation
      among Ca, Mg, Zn, Cr, Al, Mn, and Fe, all of them used as raw materials in steel
      manufacturing and/or accumulated as industrial blast furnace slag and steelworks
      slag.

PMID- 16998632
TI  - Morphologic and growth responses in Chironomus tentans to arsenic exposure.
AB  - Laboratory bioassays consisting of sediments spiked with three concentrations
      (30, 130, and 260 microg g-1 As dry wt) of arsenic (As+3) were used to assess
      morphologic responses and growth in Chironomus tentans larvae. Chironomid larvae
      were raised in contaminated sediments from egg stage to emergence, and mouthpart
      abnormalities, larval length, and larval head width were used as end points to
      determine differences between metal-spiked and control specimens. C. tentans
      exhibited significantly higher mouthpart deformity proportions, smaller body
      sizes, smaller head widths, and slower development than control larvae. Our
      results demonstrate a dose-response relationship between As and mentum
      deformities in C. tentans. However, the proportion of deformed larvae did not
      increase with time in the treatment tanks. Results demonstrate that As induces
      mouthpart abnormalities at various concentrations. This research provides more
      support for the use of chironomid abnormalities as a tool for the assessment of
      heavy-metal pollution in aquatic systems.

PMID- 16998633
TI  - Morphofunctional evidence of changes in principal and mitochondria-rich cells in
      the epidermis of the frog Rana kl. esculenta living in a polluted habitat.
AB  - The epidermis of vertebrates is the body's principal barrier against environment
      and its possible contaminants. The presence of keratins, as well as specific
      detoxifying molecules or enzyme activities, in the various epidermis layers is
      believed to be involved in providing protection from harmful environmental
      influences. Anuran integument is poorly hornified and thus permeable to some
      endogenous and exogenous compounds and thus serves as a good bioindicator of
      overall environmental conditions. In the present investigation, we studied the
      epidermis of Rana kl. esculenta adult specimens collected at two different rice
      fields, relatively unpolluted and heavily polluted, respectively. Environmental
      pollution was assayed by chemical analysis performed on both sediments and
      animals. We evaluated the structural aspects of the epidermis at both light and
      electron microscopy levels and the pattern of keratinization by
      immunohistochemistry. Furthermore, we studied the activities of some enzymes
      (acid and alkaline phosphatase, nitric oxide synthase-related nicotinamide
      adenine dinucleotide phosphate dehydrogenase, glucose-6-phosphate dehydrogenase,
      catalase, nonspecific esterases, and succinic dehydrogenase) involved mainly in
      membrane transport, xenobiotics, and oxidative metabolism. Compared with
      controls, in polluted animals we found the following results: (1) an increase in
      pollutant levels (i.e., cadmium, mercury, and lead); (2) less keratinized
      superficial cells in the epidermis; and (3) changes in most enzyme activities in
      keratinocytes and mitochondria-rich cells (particularly glucose-6-phosphate
      dehydrogenase and esterases, both important to counteract oxidative and toxic
      stress). Taken as a whole, the present data indicate the morphofunctional
      plasticity of the frog epidermis in response to environmental contamination.

PMID- 16998634
TI  - Development of stable isotope dilution quantification liquid chromatography-mass
      spectrometry method for estimation of exposure levels of bisphenol A, 4-tert
      octylphenol, 4-nonylphenol, tetrabromobisphenol A, and pentachlorophenol in
      indoor air.
AB  - The potential risks to human health and reproduction of phenolic xenoestrogens,
      such as bisphenol A (BPA), 4-tert-octylphenol (OP), 4-nonylphenol (NP),
      tetrabromobisphenol A (TBBPA), and pentachlorophenol (PCP), have not been fully
      elucidated. It is possible that healthy humans are exposed to phenolic
      xenoestrogens in their daily lives. It is also possible that the source of human
      exposure to trace amounts of phenolic xenoestrogens is indoor air. Therefore, we
      have established an accurate, sensitive, and selective method for determining
      BPA, OP, NP, TBBPA, and PCP in air samples by using stable isotope dilution
      techniques using 13C12-BPA, 4-(1-methyl) octylphenol-d5 (m-OP-d5), 13C12-TBBPA,
      13C6-PCP, and liquid chromatography-mass spectrometry (LC-MS). Air sampling
      (71/min, 24 hours), using glass filters (GB-100R, 47 mm) and Empore SDB-XD
      filters (47 mm/0.5 mm, 3M, Tokyo, Japan) and subsequent extraction by washing
      were carried out. Then the extracted sample solution was subjected to LC-MS. The
      percentage recovery of these analytes ranged from 87.0% to 101.9% (SD 0.2% to
      4.6%, n=3) with correction using the stable isotope dilution quantification
      method. The quantification limit (signal-to-noise ratio, S/N>10) in the air
      samples was 0.1 ng/m3. Our findings suggest that the LC-MS method can detect low
      levels of phenolic xenoestrogens in air samples and that these trace levels of
      analytes exist in indoor air.

PMID- 16998635
TI  - Effects of contaminants on reproductive success of aquatic birds nesting at
      Edwards Air Force Base, California.
AB  - Contamination by organochlorine pesticides (OCs), polychlorinated biphenyls,
      metals, and trace elements at Edwards Air Force Base (EAFB), located in the
      Mojave Desert, could adversely affect nesting aquatic birds, especially at the
      sewage lagoons that comprise Piute Ponds. Estimates of avian reproduction, in
      conjunction with analyses of eggs and avian foods for contaminant residues, may
      indicate the potential for negative effects on avian populations. From 1996 to
      1999, we conducted studies at the Piute Ponds area of EAFB to evaluate the
      impacts of contaminants on nesting birds. Avian reproduction was evaluated in
      1999. Eggs were collected for chemical analyses in 1996 and 1999, and African
      clawed frogs (Xenopus laevis), a likely food source, were collected for chemical
      analyses in 1998. Avian species occupying the higher trophic levels--black
      crowned night-heron (Nycticorax nycticorax), white-faced ibis (Plegadis chihi),
      and American avocet (Recurvirostra americana)--generally bioaccumulated higher
      concentrations of contaminants in their eggs. Reproductive success and egg
      hatchability of night-herons and white-faced ibises in the Piute Ponds were
      similar to results observed at other western colonies. Deformities were observed
      in only one embryo in this study, but concentrations of contaminants evaluated in
      this ibis embryo were considered insufficient to have caused the deformities.
      Because clawed frogs, a primary prey item for night-herons at Piute Ponds, had no
      detectable levels of any OCs, it is likely that OCs found in night-heron eggs
      were acquired from the wintering grounds rather than from EAFB. The presence of
      isomers of dichlorodiphenyltrichloroethane (DDT) in ibis eggs indicated recent
      exposure, but invertebrates used for food by ibises were not sampled at Piute
      Ponds, and conclusions about the source of OCs in ibis eggs could not be made.
      Concentrations of contaminants in random and failed eggs of individual species
      were not different, and we concluded that contaminants did not cause the observed
      egg failures.

PMID- 16998636
TI  - Comparative developmental toxicity of nickel to Gastrophryne carolinensis, Bufo
      terrestris, and Xenopus laevis.
AB  - The early embryo-larval developmental toxicity of nickel (Ni) to 3 amphibian
      species, Xenopus laevis (South African clawed frog), Bufo terrestris (southern
      toad), and Gastrophryne carolinensis (eastern narrow-mouthed toad), was evaluated
      using a modified FETAX model. Studies were initiated from late blastulae stage
      (Nieuwkoop and Faber [NF] stage 10 or Gosner stage 12) and completed at a common
      embryological-based test termination point, which represented the completion of
      the major stages of organogenesis (NF stage 46 for Xenopus or Gosner stage 26 for
      the toads). Results indicated that, in terms of lethality, G. carolinensis was
      the most sensitive and X. laevis was the least sensitive of the species tested.
      The 4-d LC50 in X. laevis value was approximately 7.2- and 2.8-fold greater than
      the G. carolinensis and B. terrestris, respectively. In terms of malformation, X.
      laevis was the most sensitive and B. terrestris was the least sensitive of the
      species tested. The 7-d EC50 (malformation) in B. terrestris was 10.6- and 7.0
      fold greater than X. laevis or G. carolinensis, respectively. The chronic value
      (ChV) for growth in X. laevis was nearly 4.5-fold less than the ChV for growth
      determined for B. terrestris. As with the malformation endpoint, X. laevis was
      more sensitive than the other species, which were nearly equisensitive. Overall,
      the present study provides new data regarding the toxicity of Ni to larval
      amphibian species, which may be useful in the establishment of new aquatic life
      criteria for Ni.

PMID- 16998637
TI  - Detection system of Cryptosporidium parvum oocysts by brackish water benthic
      shellfish (Corbicula japonica) as a biological indicator in river water.
AB  - The brackish water benthic shellfish, Corbicula japonica, was experimentally
      exposed to Cryptosporidium parvum oocysts at 1.51x10(4)oocysts/clam/day for 7 or
      14 days. Oocysts were predominantly eliminated through the feces of Corbicula
      japonica in both cases by microscopic and PCR methods. The fecal excretion rates
      of oocysts within 4 days after the last exposure to Corbicula japonica were 87.6%
      for the 7-day exposure group and 86.0% for the 14-day exposure group. The tissue
      residue level of oocysts in the gastrointestinal tract 3 days after the last
      exposure was 2.7% of total exposed oocysts and that of 7 days was 1.1% for the 7
      day exposure case and 1.6 and 0.5% for the 14-day exposure case, respectively,
      maintaining infectivity to cultured cells (HCT-8) in vitro. At the same time,
      field tests of Corbicula japonica for collecting oocysts showed that this clam
      could certainly collect Cryptosporidium parvum oocysts in the natural river and,
      furthermore, the gene type of C. parvum could be also identified proving its
      effectiveness as a biological indicator. The present study showed that the
      brackish water benthic shellfish Corbicula japonica may be capable of gathering
      and preserving Cryptosporidium parvum oocysts to a considerable extent under the
      natural ecological conditions, and further suggests the effectiveness of
      Corbicula japonica as a practical and general bioindicator for estimates of river
      water contamination by oocysts of Cryptosporidium parvum.

PMID- 16998638
TI  - Efficacy of anal fistula plug in closure of Crohn's anorectal fistulas.
AB  - PURPOSE: The efficacy of Surgisis anal fistula plug in closure of Crohn's
      anorectal fistula was studied. METHODS: Patients with Crohn's anorectal fistulas
      were prospectively studied. Diagnosis was made by histologic, radiographic, or
      endoscopic criteria. Variables recorded were: number of fistula tracts (primary
      openings), presence of setons, and current antitumor necrosis factor therapy.
      Under general anesthesia and in prone jackknife position, patients underwent
      irrigation of the fistula tract by using hydrogen peroxide. Each primary opening
      was occluded by using a Surgisis anal fistula plug. Superficial tracts amenable
      to fistulotomy were excluded. RESULTS: Twenty consecutive patients were
      prospectively enrolled, comprising a total of 36 fistula tracts. At final follow
      up, all fistula tracts had been successfully closed in 16 of 20 patients, for an
      overall success rate of 80 percent. Thirty of 36 individual fistula tracts (83
      percent) were closed at final follow-up. Patients with single fistulas (with 1
      primary opening) were most likely to have successful closure using the anal
      fistula plug. Successful closure was not correlated with the presence of setons
      or antitumor necrosis factor therapy. CONCLUSIONS: Closure of Crohn's anorectal
      fistula tracts using Surgisis anal fistula plug is safe and successful in 80
      percent of patients and 83 percent of fistula tracts. Closure rates were higher
      with single tracts than complex fistulas with multiple primary openings.

PMID- 16998639
TI  - A novel method of endoscopic mucosal resection assisted by submucosal injection
      of autologous blood (blood patch EMR).
AB  - PURPOSE: Endoscopic mucosal resection assisted by submucosal injection of saline
      is a widely used procedure; however, it has three limitations: 1) it often is
      difficult to maintain a desirable level of tissue elevation after the injection;
      2) the saline has no efficacy in preventing hemorrhage; 3) nothing can protect
      the site of mucosal defect after endoscopic mucosal resection to prevent
      perforation. Blood, as a new medium for use in submucosal injection, may remedy
      these drawbacks. This is the first report of this technique. METHODS: From May to
      October 2004, 28 outpatients (8 females; median, 64 years) with 35 colorectal
      polyps (median, 5 mm in diameter; range, 1-30 mm) were enrolled in this study.
      Technique of the blood patch endoscopic mucosal resection: after autologous blood
      was injected into the submucosa under the lesion using a disposable 23-gauge
      needle, the lifted mucosa with the lesion was removed using a conventional
      snaring technique. The outcomes were prospectively studied. RESULTS: Although one
      lesion was not lifted by the submucosal injection because of the submucosal
      invasion of carcinoma, 33 of the other 34 lesions (97.1 percent) were
      successfully completed using the blood patch endoscopic mucosal resection. The
      clot covered the raw surface after the endoscopic mucosal resection without
      bleeding. No complications (including hemorrhage and perforation) were observed.
      The blood patch endoscopic mucosal resection did not disturb pathologic
      examination. CONCLUSIONS: Endoscopic mucosal resection assisted by submucosal
      injection of autologous blood can be performed safely, easily, and economically.
      Autologous blood is a promising medium for submucosal injection on endoscopic
      mucosal resection.

PMID- 16998640
TI  - On the dynamics of electrically-coupled neurons with inhibitory synapses.
AB  - We study the dynamics and bifurcations of noise-free neurons coupled by gap
      junctions and inhibitory synapses, using both delayed delta functions and alpha
      functions to model the latter. We focus on the case of two cells, as in the
      studies of Chow and Kopell (2000) and Lewis and Rinzel (2003), but also show that
      stable asynchronous splay states exist for globally coupled networks of N cells
      dominated by subthreshold electrical coupling. Our results agree with those of
      Lewis and Rinzel (2003) in the weak coupling range, but our Poincare map analysis
      yields more information about global behavior and domains of attraction, and we
      show that the explicit discontinuous maps derived using delayed delta functions
      compare well with the continuous history-dependent, implicitly-defined maps
      derived from alpha functions. We find that increased bias currents, super
      threshold electrical coupling and synaptic delays promote synchrony, while sub
      threshold electrical coupling and fast synapses promote asynchrony. We compare
      our analytical results with simulations of an ionic current model of spiking
      cells, and briefly discuss implications for stimulus response modes of locus
      coeruleus and for central pattern generators.

PMID- 16998641
TI  - Systems-level modeling of neuronal circuits for leech swimming.
AB  - This paper describes a mathematical model of the neuronal central pattern
      generator (CPG) that controls the rhythmic body motion of the swimming leech. The
      systems approach is employed to capture the neuronal dynamics essential for
      generating coordinated oscillations of cell membrane potentials by a simple CPG
      architecture with a minimal number of parameters. Based on input/output data from
      physiological experiments, dynamical components (neurons and synaptic
      interactions) are first modeled individually and then integrated into a chain of
      nonlinear oscillators to form a CPG. We show through numerical simulations that
      the values of a few parameters can be estimated within physiologically reasonable
      ranges to achieve good fit of the data with respect to the phase, amplitude, and
      period. This parameter estimation leads to predictions regarding the synaptic
      coupling strength and intrinsic period gradient along the nerve cord, the latter
      of which agrees qualitatively with experimental observations.

PMID- 16998642
TI  - Mechanisms of seizure propagation in a cortical model.
AB  - We consider a mathematical model of mesoscopic human cortical ictal electrical
      activity. We compare the model results with ictal electrocortical data recorded
      from three human subjects and show how the two agree. We determine that, in the
      model system, seizures result from increased connectivity between excitatory and
      inhibitory cell populations, or from decreased connectivity within either
      excitatory or inhibitory cell populations. We compare the model results with the
      disinhibition and 4-AP models of epilepsy and suggest how the model may guide the
      development of new anticonvulsant therapies.

PMID- 16998643
TI  - Non-parametric detection of temporal order across pairwise measurements of time
      delays.
AB  - Neuronal synchronization is often associated with small time delays, and these
      delays can change as a function of stimulus properties. Investigation of time
      delays can be cumbersome if the activity of a large number of neurons is recorded
      simultaneously and neuronal synchronization is measured in a pairwise manner
      (such as the cross-correlation histograms) because the number of pairwise
      measurements increases quadratically. Here, a non-parametric statistical test is
      proposed with which one can investigate (i) the consistency of the delays across
      a large number of pairwise measurements and (ii) the consistency of the changes
      in the time delays as a function of experimental conditions. The test can be
      classified as non-parametric because it takes into account only the directions of
      the delays and thus, does not make assumptions about the distributions and the
      variances of the measurement errors.

PMID- 16998644
TI  - An unusual case of musicogenic epilepsy in a patient with a left fronto-temporal
      tumour.

PMID- 16998645
TI  - Interobserver agreement and predictive value for outcome of two rating scales for
      the amount of extravasated blood after aneurysmal subarachnoid haemorrhage.
AB  - BACKGROUND: In patients with SAH the amount of extravasated blood on the initial
      CT scan is related with delayed cerebral ischemia and clinical outcome. We
      investigated the interobserver variation of the Hijdra and Fisher scales for the
      amount of extravasated blood and the predictive values of these scales for
      delayed cerebral ischemia and outcome. METHODS: For 132 patients admitted within
      48 hours after SAH three observers assessed the amount of blood on the initial CT
      scan by means of the Hijdra and Fisher scale. We analyzed interobserver agreement
      with kappa statistics and used multivariate logistic regression for the
      association with delayed cerebral ischemia and clinical outcome. RESULTS: The
      interobserver agreement of all three pairs of observers was good for the Hijdra
      scale (kappas for total sum scores ranging from 0.67 to 0.75) and mild to
      moderate for the Fisher scale (kappas ranging from 0.37 to 0.55). For the Hijdra
      scale the risk of DCI was higher for intermediate (OR 4.2; 95% CI 1.1-16.3) and
      large (OR 3.6; 95% CI 0.8-16.4) amounts of blood with small amount as reference.
      Fisher grade III (OR 1.0; 95% CI 0.2-5.2) and IV (OR 0.3; 95% CI 0.02-4.0) were
      not related with DCI. For the Hijdra scale and clinical outcome we found an
      increasing risk for poor outcome with intermediate (OR 3.9; 95% CI 1.0-15.9) and
      large (OR 10.7; 95% CI 2.3-50.1) amounts of blood. Such a relation was not found
      for Fisher grade III (OR 1.2; 95% CI 0.2-7.0) and IV (OR 0.2; 95% CI 0.01-3.4).
      CONCLUSIONS: For the Hijdra scale we found a distinct better interobserver
      agreement than for the Fisher score. Moreover, the Hijdra scale was an
      independent prognosticator for DCI and clinical outcome, which was not the case
      for the Fisher score.

PMID- 16998646
TI  - Apoptotic cascades as possible targets for inhibiting cell death in Huntington's
      disease.
AB  - Huntington's disease (HD) is a devastating autosomal dominant disorder
      characterized by progressive motor and neuropsychological symptoms. Evidence
      implicating the apoptotic cascades as a possible cause for the neurodegeneration
      seen in HD has directed researchers toward investigating therapeutic treatments
      targeting caspases and other proapoptotic factors. Cellular and murine models,
      which have demonstrated that caspase-mediated cleavage could be the cause for the
      neurodegeneration seen in HD, have evoked more research investigating the
      possible inhibition of apoptosis in HD. In particular, minocycline, a
      tetracycline-derived antibiotic that has been shown to increase survival in
      transgenic mouse models of HD, exhibits a neuroprotective feature in HD and
      demonstrates an anti-inflammatory as well as an anti-microbial effect by
      inhibiting microglial activation known to cause apoptosis.

PMID- 16998647
TI  - Simple versus complex assessment of white matter hyperintensities in relation to
      physical performance and cognition: the LADIS study.
AB  - BACKGROUND: White matter hyperintensities (WMH) on MRI are associated with
      disorders of gait and balance and with cognitive impairment. The most suitable
      method to assess WMH in relation to the clinical evaluation of disturbances in
      these areas has not yet been established. AIM: To compare a simple visual rating
      scale, a detailed visual rating scale and volumetric assessment of WMH with
      respect to their associations with clinical measures of physical performance and
      cognition. METHODS: Data were drawn from the multicentre, multinational LADIS
      study. Data of 574 subjects were available. MRI analysis included assessment of
      WMH using the simple Fazekas scale, the more complex Scheltens scale and a semi
      automated volumetric method. Disturbances of gait and balance and general
      cognitive function were assessed using the Short Physical Performance Battery
      (SPPB) and the Mini Mental State Examination (MMSE), respectively. RESULTS:
      Irrespective of the method of measuring WMH, subjects with disturbances of gait
      and balance (SPPB < or = 10) had more WMH than subjects with normal physical
      performance. Subjects with mild cognitive deficits (MMSE < or = 25) had more WMH
      than subjects with normal cognition. Correlations between clinical measures and
      WMH were equal across methods of WMH measurement (SPPB: Spearman r = -0.22, 
      0.25, -0.26, all p < 0.001; MMSE: Spearman r = -0.11, -0.10, -0.09, all p < 0.05,
      for Fazekas scale, Scheltens scale and volumetry, respectively). These
      associations remained significant and comparable after correcting for age, gender
      and education in multivariate linear regression analyses. CONCLUSION: Simple and
      complex measures of WMH yield comparable associations with measures of physical
      performance and cognition. This suggests that a simple visual rating scale may be
      sufficient, when analyzing relationships between clinical parameters and WMH in a
      clinical setting.

PMID- 16998648
TI  - CSF protein profiling using Multiplex Immuno-assay: A potential new diagnostic
      tool for leptomeningeal metastases.
AB  - OBJECTIVE: The diagnosis of leptomeningeal metastases (LM) is based on clinical
      symptoms, magnetic resonance imaging (MRI) of brain and spine and cytological
      analysis of cerebrospinal fluid (CSF). The clinical picture of LM is highly
      variable and both cytological CSF analysis and contrast-enhanced MRI are limited
      in sensitivity. More sensitive tools are needed to diagnose LM. We measured a
      profile of proteins involved in adhesion and inflammation in the CSF of LM and
      control patients and determined their potential diagnostic value for LM. PATIENTS
      AND METHODS: Using Multiplex Immuno-Assay (MIA), the CSF concentrations of nine
      soluble adhesion molecules, cyto- and chemokines were measured in patients with
      cytologically proven LM (n = 57) and control patients with a systemic malignancy
      (n = 20), aseptic/viral meningitis (n = 11) or other (non-)neurological diseases
      (n = 19). RESULTS: We found high CSF levels of soluble Vascular Cell Adhesion
      Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1),
      Interleukin-8 (IL-8), Pulmonary and Activation Regulated Chemokine (PARC),
      Interleukin-18 (IL-18) and Interferon-gamma inducible protein (IP-10) in patients
      with LM. The CSF protein profile in LM patients differed significantly from the
      profile found in control patients. Multivariate logistic regression and ROC
      analysis showed that the MIA-measured CSF protein profile has an additive
      discriminating value for LM above standard CSF parameters. A combination of total
      protein, glucose, IL-8, PARC and IP-10 CSF levels proved to be most
      discriminative between LM and non-LM patients. CONCLUSION: Our results warrant a
      prospective study to determine whether a CSF protein profile, including IL-8,
      PARC and IP-10 has diagnostic value compared with CSF cytology, the golden
      standard for LM.

PMID- 16998649
TI  - Utility of the Mattis dementia rating scale to assess the efficacy of
      rivastigmine in dementia associated with Parkinson's disease.
AB  - INTRODUCTION: The severe, cortical, cholinergic depletion accompanying
      Parkinson's disease (PD) is considered as a highly probable correlate of
      cognitive and behavioural dysfunction. Recent studies have demonstrated that
      cholinesterase inhibitors (notably rivastigmine) are beneficial in patients
      suffering from dementia associated with PD (PDD). However, the primary efficacy
      variables used in such work came from scales designed for Alzheimer's disease
      (AD), even though the cognitive symptoms in PD and AD dementia do not overlap
      completely. The aim of the present study (a double-blind, placebo-controlled
      clinical trial) was to determine the utility of the Mattis dementia rating scale 
      the most commonly used scale in PD patients - to assess the efficacy of a 24
      week rivastigmine treatment. METHODS: Twenty-eight patients with PD, who
      constituted a subgroup of patients enrolled to the EXPRESS study (Emre et al, N
      Engl J Med 2004) participated in this study. They suffered from mild to
      moderately severe dementia (MMSE scores above 10 and below 24), with an onset of
      cognitive symptoms occurring at least two years after the diagnosis of PD.
      Patients were randomly assigned to treatment with rivastigmine (3 to 12 mg per
      day) or placebo. The Mattis dementia rating scale was administered to patients
      from six centres in France at the baseline and end-point visits. RESULTS:
      Compared with placebo, a 24-week rivastigmine treatment led to a significant
      improvement in the overall score on the Mattis dementia rating scale (p = 0.031),
      with a trend towards a significant improvement in the "Attention" subscale score
      (p = 0.061). Correlation analysis showed that in the rivastigmine group,
      performance on the Mattis "Attention" and "Initiation" subscales appeared to
      contribute heavily to the improvement in the overall score. Moreover, the latter
      was also related to an improvement in activities of daily living and a reduction
      in behavioural disturbances. DISCUSSION: By using the Mattis dementia rating
      scale (which comprises items that are sensitive to executive dysfunction), the
      present study confirmed that rivastigmine has a beneficial effect on cognitive
      function in PDD. Despite our study's small sample size, the Mattis scale was able
      to detect this improvement and could thus be considered as an interesting outcome
      measure in further work.

PMID- 16998650
TI  - Combining short interval MRI in Alzheimer's disease: Implications for therapeutic
      trials.
AB  - Cerebral atrophy calculated from serial MRI is a marker of Alzheimer's disease
      (AD) progression, and a potential outcome measure for therapeutic trials.
      Reducing within-subject variability in cerebral atrophy rates by acquiring more
      than two serial scans could allow for shorter clinical trials requiring smaller
      patient numbers. Forty-six patients with AD and 23 controls each had up to 10
      serial MR brain scans over two years. Whole brain atrophy was calculated for each
      subject from every scan-pair. 708 volumetric MRI scans were acquired: 2199
      measures of atrophy were made for patients, and 1182 for controls. A linear mixed
      model was used to characterise between and within-individual variability. These
      results were used to investigate the power of combining multiple serial scans in
      treatment trials of varying lengths. In AD, the mean whole brain atrophy rate was
      2.23%/year (95% CI: 1.90-2.56%/year). The linear mixed model was shown to fit the
      data well and led to a formula (0.99(2) + (0.82/t)2) for the variance of atrophy
      rates calculated from two scans "t" years apart. Utilising five optimally timed
      scans with repeat scans at each visit reduced the component of atrophy rate
      variance attributable to within-subject variability by approximately 56%,
      equating to a approximately 40% sample size reduction (228 vs 387 patients per
      arm to detect 20% reduction in atrophy rate) in a six-month placebo-controlled
      trial. This benefit in terms of sample size is relatively reduced in longer
      trials, although adding extra scanning visits may have benefits when patient drop
      outs are accounted for. We conclude that sample sizes required in short interval
      therapeutic trials using cerebral atrophy as an outcome measure may be reduced if
      multiple serial MRI is performed.

PMID- 16998651
TI  - A 45-year history of acquired autoimmune neuromyotonia.

PMID- 16998652
TI  - Residual fatigue is independent of antecedent events and disease severity in
      Guillain-Barre syndrome.
AB  - The occurrence of severe fatigue after Guillain-Barre syndrome (GBS), and its
      relation with disease course, clinical characteristics, and antecedent infections
      was studied in 100 GBS patients. Severe fatigue, expressed as a mean Fatigue
      Severity Scale (FSS) score of 5.0 or more, was present in 60% of all patients. It
      was more frequently present in females and in patients over 50 years (p < 0.01).
      There was no significant relationship between fatigue severity and the level of
      functional disability at nadir, antecedent events or infections, clinical
      variables, and time to follow-up after GBS.

PMID- 16998653
TI  - [Lysis therapy vs. conservative therapy: randomised and prospective study on the
      treatment of acute central retinal artery occlusion (EAGLE study)].
AB  - In the prospective, randomised and multicenter EAGLE study, the therapeutic
      efficiency of local intra-arterial fibrinolysis (LIF) versus conservative
      treatment is being tested in patients with an acute central retinal artery
      occlusion (CRAO). The most important inclusion criteria are: (1) age between 18
      75 years, (2) CRAO not older than 20 h, and (3) visual acuity <0.32. The primary
      study endpoint is the visual acuity before and 1 month after therapy. The study
      was started in 2002. To August 2006, 63 of the 200 required patients have been
      included in the study at 17 medical centers in Germany, Switzerland and Austria.

PMID- 16998656
TI  - ?

PMID- 16998655
TI  - The most important recent advances in synapse research from my point of view--and
      what remains to be done.

PMID- 16998657
TI  - [Importance of anesthesia in multimodal oncologic therapeutical concepts].
AB  - Patients with malignant diseases are increasingly being treated with multimodal
      therapeutical concepts based on the three major modalities surgery, radiotherapy
      and chemotherapy. The perioperative period is crucial within this multimodal
      concept as the prognosis of patients may be directly influenced by perioperative
      measures. In addition, it is of major importance to avoid complications in the
      perioperative phase, as these might worsen the prognosis of the patient and in
      order to prevent a delay in the beginning of planned adjuvant therapies. These
      aspects demonstrate the important role of anesthesia in the treatment of patients
      with cancer. Further studies defining the relevance of anesthesiologic measures
      in oncologic patients are needed.

PMID- 16998658
TI  - [Clinical picture of spinal tumors].
AB  - Spinal tumors may present with symptoms such as pain and motor and sensory
      deficits. Sphincter dysfunction may also occur. The clinical picture depends upon
      the size and localization of the tumor in relation to the cross section and the
      height along the longitudinal axis of the spinal cord. Typical symptoms due to
      transverse damage of the spinal cord are complete lesion, Brown-Sequard syndrome,
      a lesion of the central spinal cord, and posterior cord syndrome. Tetraparesis,
      spastic, or flaccid paraparesis result from lesions at the cervical spine,
      thoracic spine, or below the first lumbar vertebral body, respectively.

PMID- 16998659
TI  - [Whole body MRI--diagnostic strategy of the future?].
AB  - Whole body magnetic resonance imaging (MRI) opens new opportunities in diagnostic
      radiology as systemic disease entities can be examined with high sensitivity.
      This can lead to a change of paradigm, so that not only organ-related but rather
      disease-specific MRI examination protocols can be applied which focus on the
      underlying pathophysiology of the disease. Whole body MRI has already been
      successfully used for several oncological and non-oncological indications. In
      addition, whole body MRI has broadened the discussion regarding its use for
      secondary prevention. Compared to computed tomography, MRI does not use
      radiation. Although whole body MRI is still in an early stage, the enormous
      medical and economical potential can be envisioned.

PMID- 16998660
TI  - [Management of complications after angularly stable locking proximal humerus
      plate fixation].
AB  - PURPOSE: In this prospective study, complications observed after angularly stable
      proximal humerus plate fixation (locking proximal humerus plate) were analysed by
      deriving specific therapies. PATIENTS: Fifty patients (median age 65 years, range
      25-84 years, 39 female, 11 male) with displaced proximal humerus fractures (seven
      single, 36 double, and seven triple fractures) were evaluated 3, 6, and 12 months
      after angularly stable plate fixation using a standard protocol. RESULTS: Age-
      and gender-matched median constant scores 12 months postoperatively showed for
      the three fracture types 86, 87, and 55 points and complication rates of 14, 19,
      and 100%, respectively. There were seven primary and seven secondary implant
      displacements, five humeral head necroses, four osseous malalignments, two
      nonunions, two deep infections, and one heterotopic ossification. Nine
      reoperations were required in six patients: implant removal (n=3),
      reosteosynthesis (n=2), revision because of nonunion (n=2), and deep infection
      (n=2). CONCLUSIONS: Differentiated analysis of complications and the development
      of specific prevention and therapeutic strategies considering surgical technique,
      implant, fracture morphology, and humeral head perfusion minimize the rate of
      complications observed after angularly stable locking proximal humerus plate
      fixation.

PMID- 16998661
TI  - [Local recurrence of prostate cancer: hormone therapy].
AB  - BACKGROUND: The majority of patients receive HT after biochemical progression
      despite primary therapy of prostate cancer with curative intent. It is difficult
      to differentiate at a low rise in PSA level, e.g., <or=1 ng/ml, between local or
      systemic recurrence. MATERIAL AND METHODS: The PSA doubling time (DT) is the most
      reliable surrogate parameter to decide if HT should be initiated. In practice,
      however, the trigger PSA is used instead. The latter is closely related to the
      timing of HT. A high PSA is a contraindication for local salvage therapy.
      Intermittent HT is apparently as effective as continuous HT and shortens the time
      of HT exposure. RESULTS: Traditional HT employs a LHRH agonist, however, the side
      effect profile is a disadvantage due to the long duration of this treatment,
      e.g., sarcopenia, osteopenia, or even cognitive impairment. The alternative is
      nontraditional HT: nonsteroidal antiandrogen (AA) alone such as bicalutamide 150
      mg or peripheral androgen blockade (AA plus 5alpha-reductase inhibitor).
      CONCLUSION: Even after a long duration of the latter HT the side effects are less
      pronounced (gynecomastia) and treatable. Particularly in patients with high-risk
      primary tumors [Gleason score 7(4+3)-10 or an initially high PSA], nontraditional
      HT may be followed by secondary HT.

PMID- 16998662
TI  - Andrea Verga (1811-1895).

PMID- 16998663
TI  - Spontaneous regression of a cystic cavum septum pellucidum.
AB  - A persistent cavum septum pellucidum (CSP) is present in approximately 0.73% of
      adults, although its incidence ranges from 0.14 to 18.9% depending on the
      detection method. Cystic CSP is even rarer. A cyst causing mass within the CSP
      can obstruct the intraventricular foramen, leading to blockage of CSF flow and
      possible hydrocephalus, often justifying surgical intervention. We describe
      spontaneous decompression of a cystic CSP in a 36-year-old man. Initial MRI
      showed a cystic CSP with lateral bowing of the septal walls to 1.9 cm. Follow-up
      MRI 15 months later demonstrated no lateral bowing, and the septal wall width was
      1.0 cm. This spontaneous decompression was not explained by the one previously
      described case report of cystic CSP regression.

PMID- 16998664
TI  - Umbilical CSF fistula: a rare complication of ventriculoperitoneal shunt.
AB  - An umbilical CSF fistula following a ventriculoperitoneal shunt is an extremely
      rare complication. We report a 28-year-old man who presented with leak of clear
      fluid from the umbilicus, one month after a ventriculo-peritoneal shunt revision.
      Shuntogram revealed communication between umbilicus and abdominal end of the
      catheter. He was managed successfully with shunt exteriorization, antimeningitic
      treatment, and later shunt re-insertion.

PMID- 16998667
TI  - The genetics of FAP and FAP-like syndromes.
AB  - The presence of multiple adenomatous polyps in the large bowel confers a high
      lifetime risk of colorectal cancer. Although many cases of classical familial
      adenomatous polyposis (> 100 polyps) can be accounted for by mutations in the
      adenomatous polyposis coli (APC) gene, a large group of patients remains with
      multiple (5-100) adenomas and in whom there is no detectable APC mutation.
      Recently two new genetic variants have been found to be associated with multiple
      colorectal adenomas and cancer, MYH/MUTYH on chromosome 1p and the HMPS/CRAC1
      locus on chromosome 15q13-q14. New information also continues to emerge regarding
      the less common hamartomatous polyposis conditions, Peutz-Jeghers syndrome and
      Juvenile Polyposis syndrome. In approximately half to two thirds of these
      families, germline genetic variants can now be uncovered. In this review we draw
      together some of the most recent information pertinent to the molecular
      pathogenesis of colorectal polyposis.

PMID- 16998666
TI  - The history of familial adenomatous polyposis.

PMID- 16998668
TI  - Familial adenomatous polyposis: The practical applications of clinical and
      molecular screening.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant condition mostly
      due to a mutation of the APC gene on the chromosome 5q. Carriers have an almost
      100% chance of developing colorectal cancer after having multiple (typically 100s
      to 1000s) of adenomatous polyps. It is usually readily identified through this
      phenotype of multiple adenomas. Correlations between the location of the family
      specific mutation on the APC gene and clinical manifestations of the disease are
      of some assistance in clinical management, though there is heterogeneity in
      clinical course even between family members with the same mutation. FAP is
      important to recognize, as there are disease-specific management implications
      with respect to offering mutational analysis of the APC (and perhaps other) genes
      for predictive testing of other family members, endoscopic diagnostic procedures,
      surveillance planning, and surgical management. Extra-colonic manifestations,
      including duodenal polyposis, desmoid disease and other tumours, can dominate
      clinical care after colectomy. The inheritable and lethal nature of the disease,
      together with the availability of effective treatment strategies, makes a
      sensitive clinical and psychosocial approach important to maximize compliance and
      good outcomes for all members of affected families.

PMID- 16998669
TI  - In which patients do I perform IRA, and why?

PMID- 16998673
TI  - Current ideas in desmoid tumours.
AB  - Desmoid tumours are rare neoplasms of fibroblastic origin which arise with
      disproportionate frequency in patients with familial adenomatous polyposis (FAP).
      They are thought to develop in about 10-25% of FAP patients and may be the
      leading cause of death amongst those who have undergone colectomy. Risk factors
      include trauma, having a distal germline APC mutation, having a family history of
      desmoids, and probably oestrogens. In very high-risk individuals there may be a
      case for delay of colectomy or chemoprophylaxis at the time of surgery. Desmoids
      are now known to be true neoplasms but with normal telomere length and telomerase
      activity. FAP-associated tumours seem to carry biallelic APC mutations, one of
      which lies in the distal part of the gene. Such loss of wild-type APC seems to
      occur relatively late in tumour development. It is likely that beta-catenin plays
      an important role in tumourigenesis. FAP-associated desmoids tend to arise in the
      abdomen or abdominal wall. CT scanning gives the best information on tumour
      anatomy whilst T2-weighted MRI indicates likely behaviour. Treatment may simply
      consist of observation. Otherwise, usual first-line therapy is with sulindac with
      or without an anti-oestrogen. Cytotoxic chemotherapy is an option in unresectable
      tumours. Surgery is a reasonable first-line treatment in abdominal wall tumours
      but is risky for intra-abdominal tumours and may necessitate massive small bowel
      resection. Desmoids are the greatest remaining challenge in the management of FAP
      and further research into their aetiology needs to be combined with multicentre
      clinical trials of new treatments in order to improve management of the disease.

PMID- 16998675
TI  - The current status of chemoprevention in FAP.

PMID- 16998672
TI  - Surveillance and management of upper gastrointestinal disease in Familial
      Adenomatous Polyposis.
AB  - Almost all patients affected by Familial Adenomatous polyposis (FAP) will develop
      foregut as well as hindgut polyps, and following prophylactic colectomy duodenal
      cancer constitutes one of the leading causes of death in screened populations.
      Without prophylactic colectomy, FAP patients predictably develop colorectal
      cancer, but the lifetime risk of upper gastrointestinal cancer is lower,
      estimated at approximately 5%. Management of the upper gastrointestinal cancer
      risk is one of the greatest challenges facing clinicians involved in the care of
      Polyposis families, and with improved survival following prophylactic colectomy,
      the burden of foregut disease (particularly duodenal adenomatosis) will increase.
      Until recently, the value of upper gastrointestinal surveillance in FAP
      populations has been contentious, but with improved understanding of the natural
      history coupled with developments in surgery, interventional endoscopy and
      medical therapy, treatment algorithms for duodenal adenomatosis in FAP are
      becoming clearer.

PMID- 16998670
TI  - Restorative proctocolectomy and ileal pouch-anal anastomosis for familial
      adenomatous polyposis revisited.
AB  - Since restorative proctocolectomy (RPC) with ileal-pouch anal anastomosis (IPAA)
      removes the entire diseased mucosa, it has become firmly established as the
      standard operative procedure of choice for familial adenomatous polyposis (FAP).
      Many technical controversies still persist, such as mesenteric lengthening
      techniques, close rectal wall proctectomy, endoanal mucosectomy vs. double
      stapled anastomosis, loop ileostomy omission and a laparoscopic approach. Despite
      the complexity of the operation, IPAA is safe (mortality: 0.5-1%), it carries an
      acceptable risk of non-life-threatening complications (10-25%), and it achieves
      good long-term functional outcome with excellent patient satisfaction (over 95%).
      In contrast to the high incidence in patients operated for ulcerative colitis
      (UC) (15-20%), the occurrence of pouchitis after IPAA seems to be rare in FAP
      patients (0-11%). Even after IPAA, FAP patients are still at risk of developing
      adenomas (and occasional adenocarcinomas), either in the anal canal (10-31%) or
      in the ileal pouch itself (8-62%), thus requiring lifelong endoscopic monitoring.
      IPAA operation does not jeopardise pregnancy and childbirth, but it does impair
      female fecundity and has a low risk of impairment of erection and ejaculation in
      young males. The latter can almost completely be avoided by a careful "close
      rectal wall" proctectomy technique. Some argue that low risk patients (e.g. <5
      rectal polyps) can be identified where ileorectal anastomosis (IRA) might be
      reasonable. We feel that the risk of rectal cancer after IRA means that IPAA
      should be recommended for the vast majority of FAP patients. We accept that in
      some very selected cases, based on clinical and genetics data (and perhaps
      influenced by patient choice regarding female fecundity), a stepwise surgical
      strategy with a primary IPA followed at a later age by a secondary proctectomy
      with IPAA could be proposed.

PMID- 16998677
TI  - Long-term results of microscopic lymphatic vessel-isolated vein anastomosis for
      secondary lymphedema of the lower extremities.
AB  - PURPOSE: To evaluate the effectiveness of microscopic lymphatic vessel-isolated
      vein anastomosis in patients with secondary obstructive lymphedema of a lower
      extremity, refractory to nonoperative management. METHODS: Nine women suffered
      from nonpitting edema of one or both legs (11 limbs) after radical hysterectomy
      with postoperative irradiation for uterine cancer. The indications for this
      operation were repeated cellulitis and severe nonpitting edema impairing limb
      function. Under microscopy of 3.2 on average, the identified lymphatic vessels
      were anastomosed to an isolated saphenous vein using the pull-through technique
      with modifications. RESULTS: The follow-up period ranged from 21 to 87 months and
      the operation achieved excellent reduction, of more than 5 cm, in six limbs; good
      reduction, of 2-5 cm, in two limbs; and poor reduction, of less than 2 cm, in
      three limbs. The frequency of cellulitis decreased from 2.4 infections per
      patient per year to 0.2 infections per patient per year. CONCLUSION: These
      results show that microscopic lymphatic vessel-isolated vein anastomosis is a
      minimally invasive operation, with good long-term effects, making it the
      treatment of choice for intractable secondary lymphedema of the lower extremities
      refractory to physiotherapy.

PMID- 16998678
TI  - Optimal timing for surgical treatment to prevent recurrence of spontaneous
      pneumothorax.
AB  - PURPOSE: Persistent air leakage and recurrence are the most common indications
      for the surgical treatment of spontaneous pneumothorax; however, the optimal
      timing for surgery is still unclear. METHODS: The subjects of this study were 90
      patients treated for either primary spontaneous pneumothorax (PSP; n = 58) or
      secondary spontaneous pneumothorax (SSP; n = 32). We compared the incidence of
      prolonged air leak, the rate of recurrence of pneumothorax, the time from the
      first episode of pneumothorax to recurrence, and the postoperative complications
      in the two groups. We also analyzed the recurrence rate after treatment with
      observation and tube drainage versus surgery. RESULTS: Seventy-three patients
      were treated with tube thoracostomy or oxygen therapy for the first episode of
      pneumothorax. Surgery was performed in 32 patients; for the first episode of
      pneumothorax in 17 and for the second or third episode in 15. Postoperative
      complications developed in six (18.7%) patients and 24 of 73 patients who did not
      undergo thoracotomy suffered recurrence. The incidence of a second episode was
      32.9% and the incidence of a third episode in the 18 patients who suffered
      recurrence after conservative treatment was 61.1%. None of the patients who
      underwent surgery suffered recurrence. CONCLUSIONS: Tube thoracostomy is still
      the treatment of choice for first-time spontaneous pneumothorax. However, because
      the incidence of a third episode of pneumothorax after conservative treatment is
      high, surgical treatment should always be considered for patients with
      recurrence. In short, surgical intervention is safe and effective and minimizes
      the chance of recurrence of both PSP and SSP.

PMID- 16998680
TI  - Lower esophageal sphincter- and vagus-preserving proximal partial gastrectomy for
      early cancer of the gastric cardia.
AB  - PURPOSE: Proximal gastrectomy and lymph node dissection are often performed for
      T1 cancer of the gastric cardia; however, direct esophagogastrostomy is
      frequently complicated by reflux esophagitis. We describe a simple technique for
      preventing esophageal reflux and discuss its results. METHODS: This technique is
      indicated for T1 cancer of the gastric cardia without lymphadenopathy. Partial
      resection, including the lesion, is performed, preserving the vagus nerve and
      lower esophageal sphincter (LES). Lymph node dissection is done around the left
      gastric, celiac, and splenic arteries. The esophagus is then anastomosed to the
      anterior wall in the center of the remnant stomach. RESULTS: We evaluated the
      results of this procedure in eight patients. X-ray films showed no esophageal
      reflux in either the supine or the right decubitus position. None of the patients
      complained of reflux or other dyscrasic symptoms, and none had any feeling of
      microgastria. One patient had some localized erosion near the anastomosis.
      CONCLUSIONS: This simple and safe technique does not result in post-gastrectomy
      syndrome or microgastria, and the risk of leaving cancer cells is minimal.

PMID- 16998679
TI  - Long-term outcome after resection of non-small cell lung carcinoma complicated by
      pneumoconiosis.
AB  - PURPOSE: Lung cancer resection in patients with respiratory complications is
      associated with a high surgical risk and the operative indications are usually
      serious. Consequently, the long-term results are unclear. We aimed to clarify the
      validity of surgery for non-small cell lung cancer (NSCLC) in patients with
      pneumoconiosis. METHODS: We reviewed the clinical and pathological data of 122
      patients undergoing resection of NSCLC with pneumoconiosis (n = 34: group A) or
      without pneumoconiosis (n = 88: group B) to assess treatment outcomes and
      prognostic factors. RESULTS: Among the treatment factors, intraoperative blood
      loss was significantly greater in group A (723.2 +/- 647.3 ml) than in group B
      (466.4 +/- 450.7 ml) (P = 0.0067), although the operative times (207 +/- 103.4
      min vs 196.1 +/- 53.5 min, respectively) and postoperative drainage period (8.3
      +/- 4.2 days vs 8.5 +/- 5.7 days, respectively) did not differ significantly
      between the two groups (P = 0.9466 and P = 0.6355, respectively). Among the
      postoperative complications, the incidence of hemorrhage was significantly higher
      in group A (29.4%) than in group B (7.9%) (P = 0.0022). The 5-year survival rates
      did not differ significantly between the two groups, (45.9% and 55.7% for groups
      A and B respectively) (P = 0.9424). CONCLUSIONS: The coexistence of
      pneumoconiosis does not adversely affect postoperative survival or the treatment
      of NSCLC, although it is associated with increased intraoperative blood loss and
      postoperative hemorrhage. Thus, if precautions are taken to minimize hemorrhage,
      surgery cannot be excluded as a treatment option for NSCLC in patients with
      pneumoconiosis.

PMID- 16998681
TI  - Value of carcinoembryonic antigen assay in predicting hepatic metastases, local
      recurrence, and survival after curative resection of colorectal cancer.
AB  - PURPOSE: We measured carcinoembryonic antigen (CEA) levels in peripheral and
      portal venous blood, and bile from patients with colorectal cancer, to determine
      its role in predicting hepatic metastases, local recurrence, and survival.
      METHODS: The subjects were 73 patients who underwent curative surgery for
      colorectal cancer. RESULTS: The median serum, bile, and portal CEA levels were
      significantly lower in 5-year survivors than in patients in whom hepatic
      metastases or recurrent disease subsequently developed. The CEA level in portal
      blood and bile was a good indicator of hepatic metastases, with sensitivity of
      92% and 100%, respectively. However, the accuracy of any CEA measurement for
      predicting hepatic metastases, local recurrence, or 5-year survival did not
      exceed 70%. CONCLUSIONS: None of these CEA measurements is accurate enough to be
      the basis of a management decision. Thus, we suggest that CEA measurement be used
      to assist in the prediction of a high risk of the development of hepatic
      secondaries and that these patients are followed up closely after curative
      resection.

PMID- 16998682
TI  - Histological features of human papilloma virus 16 and its association with the
      development and progression of anal squamous cell carcinoma.
AB  - PURPOSE: To investigate the development of anal squamous cell carcinoma (SCC) and
      the expression patterns of human papillomavirus (HPV). METHODS: We performed
      typing of HPV-DNA using a polymerase chain reaction (PCR), and amplified the
      Duchenne muscular dystrophy (DMD) genes simultaneously, to investigate the tumor
      DNA state. The expression patterns of HPV in the cancer cell nuclei was
      investigated by in situ hybridization (ISH) using HPV probes. RESULTS:
      Amplification of DMD genes was confirmed in 8 of 20 patients with anal SCC,
      suggesting that tumor DNA was preserved in these patients. In seven of these
      eight patients, only HPV16 was detected by both PCR and ISH, suggesting HPV16
      induced carcinogenesis. In two patients with carcinoma in situ (CIS), the cancer
      cells showed only a diffuse pattern (DP), and in two patients with invasive
      cancer, the cancer cell showed only an oligo-dot pattern (OP). In one patient
      with lesions ranging from CIS to invasive cancer, the histologic features varied
      in each area, from DP to OP. This change originated in the deep part of the
      microinvasive area. CONCLUSIONS: These findings show that HPV16 infection is
      closely involved in the development of anal SCC and suggest that the change in
      the genome occurs at the stage of microinvasive cancer.

PMID- 16998683
TI  - Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular
      carcinoma and intrahepatic cholangiocarcinoma.
AB  - PURPOSE: Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare
      primary hepatic neoplasm (PHN) with features of both hepatocellular and biliary
      differentiation. We compared the outcome of hepatic resection in patients with
      HCC-CC, those with hepatocellular carcinoma (HCC), and those with
      cholangiocarcinoma (ICC). METHODS: Between November 1994 and December 2003, 952
      patients underwent hepatic resection for a PHN. RESULTS: The incidence of HCC-CC
      was 3.5%. Hepatitis B surface antigen was positive in 51.2% of these patients and
      the HCV antibody was positive in 12.2%. Positive hepatitis serology was more
      common in the HCC group (66.7%). The prevalence of underlying liver cirrhosis was
      significantly lower in the ICC group (7.8%) than in the HCC (49%) and HCC-CC
      (41.5%) groups (P < 0.0001). The median overall survival periods after hepatic
      resection of HCC-CC, HCC, and ICC were 47.3, 71.7, and 21.5 months, respectively
      (P < 0.0001). The median disease-free survival (DFS) periods after hepatic
      resection for HCC-CC, HCC, and ICC were 23.4, 68.2, and 15.5 months, respectively
      (P < 0.0001). CONCLUSION: Patients with transitional type HCC-CC had
      significantly poorer survival rates than those with HCC, after hepatic resection.
      Therefore, a more aggressive treatment modality should be explored to improve the
      survival rate of these patients.

PMID- 16998684
TI  - Jejunal loop drainage versus direct pancreatic duct drainage after pancreatic
      head resection.
AB  - PURPOSE: Perioperative mortality after pancreatic head resection has fallen to
      below 5% in high-volume centers, but dehiscence of the pancreatojejunostomy
      remains a major concern. Despite various methods of protection, insufficiency
      rates still range from 6% to 19%. External drainage of pancreatic juice from the
      anastomotic site has shown promising results in the last decade. We compared the
      morbidity and mortality of two widely used drainage systems. METHODS: The
      subjects were 143 patients who underwent pancreatic head resection, followed by
      jejunal loop drainage with the top of the drain being placed between the
      pancreatojejunostomy and hepaticojejunostomy in 89, and by direct drainage of the
      pancreatic duct in 54. RESULTS: The median age was similar in both groups.
      Pancreatic fistula developed in 3 (5%) patients with a pancreatic drain and 6
      (7%) with a loop drain. Breakdown of the pancreatojejunostomy occurred in 1 (2%)
      patient with a pancreatic drain and 2 (2%) with a loop drain. The overall
      perioperative mortality was 0.7%. The surgical and medical complications and
      postoperative course were similar in the two groups. CONCLUSION: The choice of
      drainage system did not impact on the number or severity of postoperative
      complications or survival, indicating that loop drainage is as safe and effective
      as direct pancreatic duct drainage.

PMID- 16998685
TI  - Comparison of monopolar electrocoagulation, bipolar electrocoagulation,
      Ultracision, and Ligasure.
AB  - PURPOSE: Hemostasis is a fundamental principle of surgery. We compared the safety
      and efficacy of monopolar electrocoagulation (ME), bipolar electrocoagulation
      (BE), Ligasure (LS), a modern bipolar vessel sealing system, and Ultracision
      (UC), a system of ultrasound energy based shears. We also studied the healing
      process after their use. METHODS: We used each of the above methods to coagulate
      and divide the short gastric vessels of 16 white male New Zealand rabbits. The
      animals were killed after 3, 7, 14, or 21 days, and the coagulation sites and the
      adjacent gastric wall were examined histologically. RESULTS: LS and UC achieved
      complete hemostasis without any complications. Conversely, ME and BE often
      resulted in failed coagulation and perforation of the neighboring gastric wall
      from a side thermal injury. Histologically, LS demonstrated the mildest side
      thermal injury and the fastest healing process. We noted greater thermal injury
      and inflammatory response after UC than after LS on days 7 and 14; however, ME
      and BE caused the most severe lesions. CONCLUSIONS: LS and UC are clearly the
      safest and most efficient methods of coagulation, whereas ME and BE could cause
      serious clinical and histological complications. We found histological evidence
      that UC causes a slightly greater inflammatory response than LS, and the clinical
      implications of this warrant further investigation.

PMID- 16998686
TI  - Bizarre presentation of epigastric heteropagus: report of a case.
AB  - We report an unusual case of epigastric heteropagus in a female neonate. The
      parasite had a single lung as well as a liver, stomach, intestine, pancreas,
      ovaries, a single kidney, and a bladder. These visceral organs were located in
      the abdominal and pelvic space of the autosite, and the pelvic bone and lower
      legs of the parasite were fused with the respective organs in the autosite. The
      infant underwent operations to remove the central leg and some of the intra
      abdominal organs of the parasite, but she must still undergo further surgery to
      remove the genitourinary organs and pelvic bones of the parasite, and repair her
      very abducted and rotated right leg.

PMID- 16998687
TI  - Simultaneous bilateral spontaneous pneumothorax secondary to metastatic
      angiosarcoma of the scalp: report of a case.
AB  - Angiosarcoma is a highly malignant neoplasm, which most often develops on the
      scalp or face of elderly people. Common distant metastatic sites include the
      lung, liver, lymph nodes, and skin. We report a case of angiosarcoma manifesting
      as simultaneous bilateral spontaneous pneumothorax secondary to pulmonary
      metastases in an 86-year-old man. The pneumothorax preceded the diagnosis of
      angiosarcoma. Chest computed tomography showed multiple thin-walled cavitary
      metastatic pulmonary lesions, which increased in size as new lesions appeared
      over the clinical course of several months. This case suggests that a finding of
      simultaneous bilateral spontaneous pneumothorax may indicate a serious
      parenchymal lung disorder.

PMID- 16998688
TI  - Spontaneous arterial recanalization with magnetic resonance angiography evidence:
      report of a case.
AB  - A 27-year-old man was admitted to our hospital for investigation of severe
      claudication in his right foot. Based on the findings of magnetic resonance
      imaging (MRI) and magnetic resonance angiography (MRA), we diagnosed anatomic
      popliteal artery entrapment syndrome, which was causing a short popliteal artery
      occlusion. Moreover, a long posterior tibial artery occlusion and a peroneal
      artery lesion had developed as distal thromboembolic complications of the
      entrapment. Thus, we planned to perform in situ vein bypass graft for the
      popliteal occlusion and start thrombolytic treatment for the posterior tibial and
      peroneal lesions. While contemplating the operation, the patient showed a gradual
      clinical improvement over the next 2 months. A second MRA showed total arterial
      recanalization of the right posterior tibial and peroneal arteries, although the
      popliteal artery was still occluded. Spontaneous lower limb arterial
      recanalization is a rare phenomenon. To our knowledge, this is the first case of
      spontaneous arterial recanalization after a distal thromboembolic event caused by
      popliteal entrapment syndrome.

PMID- 16998689
TI  - Aortic valve myxoma mimicking vegetation: report of a case.
AB  - We report a case of cardiac myxoma of the aortic valve. To our knowledge, this
      represents only the seventh such case ever documented. A 61-year-old woman
      underwent an echocardiography to screen for hypertensive-diabetic cardiac
      complications, which showed a mass on her aortic valve. Although she had not
      experienced a fever, the mass closely resembled a vegetation, resulting in an
      initial diagnosis of infective endocarditis. We extirpated the mass and repaired
      the aortic valve with the patient under cardiopulmonary bypass. The postoperative
      course was uneventful. Histological examination confirmed that the mass was a
      myxoma.

PMID- 16998690
TI  - Successful treatment of multiple small-bowel perforations caused by
      cytomegalovirus in a patient with malignant lymphoma: report of a case.
AB  - We report the successful management of multiple small-bowel perforations caused
      by cytomegalovirus (CMV) infection in a 60-year-old man, 1 day after CHOP
      (cyclophosphamide/doxorubicin/vincristine/prednisone) therapy induction for
      malignant lymphoma. Emergency laparotomy was performed for perforative
      peritonitis, but we did not resect the lesions at this time. Instead, we
      exteriorized the small bowel and then irrigated the peritoneal cavity and
      intestinal tract. His white blood cell count was low, at 200 cells/microl, so
      this therapy was continued until it recovered. The intestine was highly
      edematous, but it improved after irrigation with peritoneal dialysis solution. In
      the second-stage procedure, we resected the small bowel with the perforations,
      and constructed a jejunostomy and colostomy, then closed the abdominal cavity.
      Although the patient needed central venous hyperalimentation, he had a favorable
      postoperative course and started treatment again for the malignant lymphoma.

PMID- 16998691
TI  - Granular cell tumor as an unusual cause of obstruction at the hepatic hilum:
      report of a case.
AB  - A diagnosis of malignancy is reasonably assumed when a lesion is found at the
      hilum or bile ducts in a patient with jaundice who has never undergone biliary
      surgery. Although benign tumors occasionally develop in this location,
      preoperative recognition is difficult and most are treated as malignant lesions.
      We illustrate this clinical scenario in this case report of a granular cell tumor
      (GCT) that developed at the biliary bifurcation, necessitating right hemi
      hepatectomy with extrahepatic biliary tree excision. We describe the clinical
      presentation, imaging findings, treatment, and histological findings of this
      tumor. Although rare, a GCT can develop at the hilum and mimic a malignant lesion
      such as cholangiocarcinoma (CC) radiologically. To our knowledge, this is the
      fourth report of a GCT at the hilum of the liver. However, the possibility of
      this tumor should be considered in the differential diagnosis of a lesion in this
      location.

PMID- 16998692
TI  - Hepatopulmonary fistula caused by alveolar echinococcosis: report of a case.
AB  - Alveolar echinococcosis is a parasitosis endemic to red fox habitats in the
      northern hemisphere. The liver is the most commonly affected organ, followed by
      the lungs. We report the case of an elderly woman with hepatic alveolar
      echinococcosis (HAE) complicated by a hepatopulmonary fistula. We performed a one
      stage operation for the hepatic and pulmonary lesions through the
      transdiaphragmatic route via a laparotomy. We report this case to emphasize that
      the first-line treatment for a hepatopulmonary fistula caused by HAE should be
      radical surgery, which results in relief of symptoms and a good outcome.

PMID- 16998693
TI  - Closure of duodenocutaneous fistula due to recurrent colon cancer with a pedicled
      jejunal seromuscular flap.
AB  - A new approach to closing a malignant enterocutaneous fistula is reported.
      Transverse colon cancer recurred around the superior mesenteric vein along with a
      duodenocutaneous fistula, thus causing severe dermatitis. The tumor was partially
      resected at the fascia level and the fistula measured 2.5 cm in diameter. A left
      rectus abdominis musculocutaneous flap failed to close the fistula because of
      graft necrosis. A jejunal flap measuring 8 cm in length was prepared by
      sacrificing about 15 cm of adjacent jejunum to create the pedicle. The mucosal
      layer of the flap was removed and the fistula was closed, then the tumor surface
      was covered. Two weeks later, the skin defect was covered with free skin
      grafting. The patient died of cancer 6 months after surgery, but there was no
      recurrence of the fistula.

PMID- 16998694
TI  - Comment on: a clinicopathological investigation of "tumor nodules" in colorectal
      cancer.

PMID- 16998695
TI  - Incentive for a shift from modern scientific medicine to integrative medicine.
AB  - Medicine has been evaluated in recent years both quantitatively and
      qualitatively. Contemporary medicine has been assumed to be conceptually based on
      modern science. However, there is a problem that quantity and quality are hard to
      evaluate using only scientific parameters. It is, therefore, the aim of this
      article to emphasize that the quantity and quality of medicine need to be
      evaluated not only from the standpoint of modern scientific medicine but also in
      terms of integrative medicine. Integrative medicine is postulated to be
      comprehensive in its fundamental doctrine, emphasizing a holistic approach
      including technical, artistic, social, religious, philosophical, and ethical
      elements. However, in evaluating carefully and seriously actual performance, it
      was noted that contemporary medicine has been giving greater emphasis to aspects
      of integrative medicine where increasing concern is paid to patients' personal
      preferences, as indicated by their quality of life. An incentive for a shift from
      exclusively scientific to integrative medicine, which started as early as the
      1970s, is revival emotion toward a prime modality of medicine.

PMID- 16998696
TI  - Present status and perspectives of bioartificial kidneys.
AB  - Currently, hemodialysis is not adequate as a renal replacement therapy because it
      provides intermittent treatment and does not provide the metabolic function of
      renal tubules. The next generation of artificial kidney should replace
      intermittent hemodialysis with continuous hemofiltration and provide the full
      metabolic function of renal tubules. The current decade has witnessed the
      development of bioartificial kidneys using artificial membranes and renal tubular
      epithelial cells. Active transport and metabolic functions were confirmed in the
      confluent monolayers of tubular cells on artificial membranes. Bioartificial
      kidneys have succeeded in improving the prognosis of patients with multiple organ
      dysfunction, presumably by lowering plasma cytokine levels in patients. For
      successful treatment of chronic renal failure using bioartificial kidneys, it is
      necessary to overcome some technical hurdles such as improving the
      antithrombogenic properties of the surface of artificial membranes and prolonging
      the function of renal tubule cells on an artificial membrane. Transfection of
      functional protein genes into renal tubule cells enables bioartificial tubule
      devices to increase their transport capacity and metabolic functions such as
      digoxin secretion and water transport. The development of wearable roller pumps
      is also essential for the clinical application of a continuous treatment system.

PMID- 16998697
TI  - Education and research using experimental pigs in a medical school.
AB  - Medium-sized animals such as miniature pigs are considered to be important for
      education and training in medical schools to master the skills required in
      surgical treatment. Much still remains to be done to establish total management
      for animal experiments using pigs. Improvement of the effective utilization of
      pigs is also required from the economical and ethical points of view. We have
      been providing a support system at a facility for experimental animals in a
      medical school for 3 years, and herein we introduce our personal experiments as
      an instructional lecture. Before starting surgical training using live pigs,
      sufficient education concerning animal ethics and dry laboratory training was
      completed. Four kinds of miniature pigs have been used as experimental animals;
      porcine rearing pens have been improved and a postoperative care system has been
      implemented. Moreover, staff at the center offer a preoperative service of
      anesthesia for surgical education, training, and research. Chronic experiments
      have increased to represent 35% and 48% of experiments using pigs in 2003 and
      2004, respectively. Experimental pigs have undergone secondary use after being
      killed to reduce the number of animals used in experiments. Sharing and reuse
      have allowed effective use of miniature pig tissues and cells for research, and
      have reduced the number of animals used. We recommend that researchers consider
      use of our total systems because they can improve the quality of medical
      education and research and facilitate effective use of tissues and cells by
      sharing and reuse among different departments.

PMID- 16998698
TI  - Suppressive effect of phosphodiesterase type 4 inhibition on systemic
      inflammatory responses after cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) induces excessive production of endogenous
      proinflammatory mediators such as cytokines and elastase, which are responsible
      for the subsequent development of systemic inflammatory response syndrome (SIRS).
      In this study, we investigated the protective effect of rolipram against SIRS
      after CPB. Rats were divided into three groups (n = 5 in each): control (C),
      rolipram (R), and sham (S). Rats in groups C and R underwent CPB for 60 min
      followed by 60 min of observation, while those in group S were observed for 120
      min without CPB. In group R, 40 microg/kg/min of rolipram was intravenously
      administered throughout the experiment. CD11b expression on neutrophils was
      analyzed using flow cytometry. Serum concentrations of tissue necrosis factor
      alpha (TNF-alpha), interleukin 1beta (IL-1beta), macrophage inflammatory protein
      2 (MIP-2), and elastase were also determined. CD11b expression at the end of the
      experiment was unchanged from the initial value in group R, whereas that in group
      C increased to almost double, and that in group S also showed a slight increase
      (P < 0.01). Serum TNF-alpha levels in groups R and S were lower than those
      observed in group C (P < 0.05). Serum IL-1beta and MIP-2 levels in groups C and R
      tended to be higher than those in group S, although the difference was not
      statistically significant. Regarding elastase, group R showed a significantly
      lower value than group C and a higher value than group S (P < 0.05).
      Phosphodiesterase type 4 inhibition seems to suppress CPB-induced SIRS through
      the regulation of proinflammatory mediators in this rat model.

PMID- 16998699
TI  - Midterm results for endovascular stent grafts via median sternotomy for distal
      aortic arch aneurysm.
AB  - Dislocation or perigraft leakage is a major problem during the follow-up period
      for endovascular stent graft (EVG) implantation via median sternotomy for distal
      aortic arch aneurysm. Anchoring sutures have been applied for the prevention of
      these complications. Here, we evaluate the midterm results and the efficacy of
      anchoring sutures. There were 21 male and 2 female patients enrolled in the study
      with an average age of 70 years (59-83). Aneurysm types were 21 true aneurysms
      (13 fusiform, 8 saccular), 1 chronic dissection, and 1 penetrating aortic ulcer.
      Total arch replacement was performed in two patients and aortocoronary bypass
      grafting was combined in four patients. Anchoring sutures to fix the EVG via
      median sternotomy were applied for 11 recent patients. The average follow-up
      period was 44 (22-79) months. There were no operative mortalities, but one case
      of paraplegia, one of stroke, and two of temporary spinal cord dysfunction.
      Complications related to EVG via median sternotomy occurred in five patients who
      had not received anchoring sutures, but the 11 patients with anchoring sutures
      showed no EVG-related complications. A chronic type B dissection revealed
      impending rupture due to false lumen infection 1 year after operation and repeat
      surgery was performed. Stent dislocation occurred in four patients, two of whom
      required repeat surgery via left thoracotomy due to endoleakage 3 and 4 years
      after surgery. One died from aneurismal rupture 5 years after surgery. One
      required emergency graft replacement because of graft perforation 5 years after
      surgery. The proportion of patients free from EVG-related events at 5 years after
      surgery was 75%. Anchoring sutures (P = 0.0155) and a large aneurysm of more than
      80 mm (P = 0.0190) were predictors of late EVG-related complications. There were
      five late deaths: two were from stroke, one from rupture, one from cancer, and
      one from multiple organ failure after repeat surgery. EVG shortens postoperative
      recovery with relatively lower mortality, but spinal cord injury is a
      complication occurring with a relatively high rate. Patients with large aneurysms
      are not good candidates for EVG implantation via median sternotomy Anchoring
      sutures to fix the EVG to the aortic wall should help prevent EVG-related events
      and improve the durability of EVG.

PMID- 16998700
TI  - Mechanism for cavitation of monoleaflet and bileaflet valves in an artificial
      heart.
AB  - It is possible that mechanical heart valves mounted in an artificial heart close
      much faster than those used for clinical valve replacement, resulting in the
      formation of cavitation bubbles. In this study, the mechanism for mechanical
      heart cavitation was investigated using the Medtronic Hall monoleaflet valve and
      the Sorin Bicarbon bileaflet valve mounted at the mitral position in an
      electrohydraulic total artificial heart. The valve-closing velocity was measured
      with a charge-coupled device (CCD) laser displacement sensor, and images of
      mechanical heart valve cavitation were recorded using a high-speed video camera.
      The valve-closing velocity of the Sorin Bicarbon bileaflet valve was lower than
      that of the Medtronic Hall monoleaflet valve. Most of the cavitation bubbles
      generated by the monoleaflet valve were observed near the valve stop; with the
      Sorin Bicarbon bileaflet valve, cavitation bubbles were concentrated along the
      leaflet tip. The cavitation density increased as the valve-closing velocity and
      the valve stop area increased. These results strongly indicate that squeeze flow
      holds the key to cavitation in the mechanical heart valve. From the perspective
      of squeeze flow, bileaflet valves with a low valve-closing velocity and a small
      valve stop area may cause less blood cell damage than monoleaflet valves.

PMID- 16998701
TI  - Evaluation of coagulant activity after mechanical heart valve replacement.
AB  - Long-term oral anticoagulant therapy is required for recipients of mechanical
      heart valves. In our hospital, the international normalized ratio of prothrombin
      time (PT-INR) has been set in the range 1.5-2.5 since October 2001. To evaluate
      whether coagulant activity is fully suppressed by this target range, coagulant
      activity was evaluated by measuring thrombin-antithrombin III complex (TAT)
      levels and valve-related complications were investigated retrospectively. Two
      hundred twenty-three patients who underwent mechanical valve replacement were
      enrolled in this study. PT-INR and TAT were measured at our outpatient clinic in
      March 2005 and valve-related complications since October 2001, when we started to
      control PT-INR in the range 1.5-2.5, were investigated. Under adequate warfarin
      control, there was no significant correlation between PT-INR and TAT, however
      nine patients who exhibited a PT-INR of less than 2.0 had high levels of TAT. And
      in atrial fibrillation (AF) patients after mitral valve replacement (MVR), the
      level of TAT was significantly high compared with sinus rhythm patients after
      atrial valve replacement. Valve-related complications were bleeding events at
      2.75% per patient year and thromboembolism at 0.32% per patient year. Attention
      to complications of thromboembolism is necessary when the PT-INR is less than
      2.0, especially in AF patients after MVR and in those with a thrombotic past
      history or high levels of TAT. The monitoring of TAT is useful in detecting
      potential coagulation factors and to determine the therapeutic range of warfarin
      that can normalize coagulant activity.

PMID- 16998702
TI  - Dynamic particle image velocimetry flow analysis of the flow field immediately
      downstream of bileaflet mechanical mitral prostheses.
AB  - New dynamic particle image velocimetry (PIV) technology was applied to the study
      of the flow field associated with prosthetic heart valves. Four bileaflet
      prostheses, the St. Jude Medical (SJM) valve, the On-X valve with straight
      leaflets, the Jyros (JR) valve, and the Edwards MIRA (MIRA) valve with curved
      leaflets, were tested in the mitral position under pulsatile flow conditions to
      find the effect of the leaflet shape and overall valve design on the flow field,
      particularly in terms of the turbulent stress distribution, which may influence
      hemolysis, platelet activation, and thrombus formation. Comparison of the time
      resolved flow fields associated with the opening, accelerating, peak, and closing
      phases of the diastolic flow revealed the effects of the leaflet shape and
      overall valve design on the flow field. Anatomically and antianatomically
      oriented bileaflet valves were also compared in the mitral position to study the
      effects of the orientation on the downstream flow field. The experimental program
      used a dynamic PIV system utilizing a high-speed, high-resolution video camera to
      map the true time-resolved velocity field inside the simulated ventricle. Based
      on the experimental data, the following general conclusions can be made. High
      resolution dynamic PIV can capture true chronological changes in the velocity and
      turbulence fields. In the vertical measuring plane that passes the centers of
      both the aortic and mitral valves (A-A section), bileaflet valves show clear and
      simple circulatory flow patterns when the valve is installed in the
      antianatomical orientation. The SJM, the On-X, and the MIRA valves maintain a
      relatively high velocity through the central orifice. The curved leaflets of the
      JR valve generate higher velocities with a divergent flow during the accelerating
      and peak flow phases when the valve is installed in the anatomical orientation.
      In the velocity field directly below the mitral valve and normal to the previous
      measuring plane (B-B section), where characteristic differences in valve design
      on the three-dimensional flow should be visible, the symmetrical divergent nature
      of the flow generated by the two inclined half-disks installed in the
      antianatomical orientation was evident. The SJM valve, with a central downward
      flow near the valve, is contrasted with the JR valve, which has a peripherally
      strong downward circulation with higher turbulent stresses. The On-X valve has a
      strong central downward flow attributable to its large opening angle and flared
      inlet shape. The MIRA valve also has a relatively strong downward central flow.
      The MIRA valve, however, diverts the flow three-dimensionally due to its
      peripherally curved leaflets.

PMID- 16998703
TI  - Changes in expression of genes related to cell proliferation in human mesenchymal
      stem cells during in vitro culture in comparison with cancer cells.
AB  - We investigated the expression levels of several genes related to cell
      proliferation in human mesenchymal stem cells (hMSCs) during in vitro culture for
      use in clinical applications. In this study, we focused on the relationship
      between hMSC proliferation and transforming growth factor beta (TGFbeta)
      signaling during in vitro culture. The proliferation rate of hMSCs gradually
      decreased and marked changes in hMSC morphology were not observed in 3 months of
      in vitro culture. The mRNA expressions of TGFbeta1, TGFbeta2, and TGFbeta
      receptor type I (TGFbetaRI) in hMSCs increased with the length of cell culture.
      There had been no change in the TGFbeta3, TGFbetaRII, and TGFbetaRIII mRNA
      expressions by the 12th passage from the primary culture (at about 3 months). The
      mRNA expression of Smad3 increased, but those of c-myc and nucleostemin decreased
      with the length of hMSC in vitro culture. In addition, the expression profiles of
      the genes that regulate cellular proliferation in hMSCs were significantly
      different from those of cancer cells. In conclusion, hMSCs derived from bone
      marrow seldom underwent spontaneous transformation during 1-2 months of in vitro
      culture for use in clinical applications. In hMSCs as well as in epithelial
      cells, growth might be controlled by the TGFbeta family signaling.

PMID- 16998704
TI  - Fabrication of transplantable human oral mucosal epithelial cell sheets using
      temperature-responsive culture inserts without feeder layer cells.
AB  - To exclude bacteria- or animal-derived factors from cultured fabrication of
      transplantable epithelial cell sheets, primary human oral mucosal epithelial
      cells were seeded on temperature-responsive culture inserts having submicron
      scale pores. Supplying culture medium containing human autologous serum to both
      apical and basal sides of human epithelial cells allows these cells to grow to
      confluence. These proliferating cells created stratified epithelial layers even
      when 3T3 feeder layers and fetal bovine serum were eliminated from culture.
      Normal keratin expression profiles were obtained with these cells, and basal and
      midlayer cells expressed p63, a putative stem/progenitor marker. These results
      suggest that temperature-responsive culture inserts can be useful in clinical
      settings that require the exclusion of xenogeneic factors.

PMID- 16998705
TI  - Design and assessment of the new APS dialyzer (APS-SA series).
AB  - Dialyzer performance seems to greatly depend on the hollow-fiber membrane
      performance, the morphology of the hollow-fiber membrane bundles (e.g., wave
      shaped hollow-fiber membrane bundles), and the design of the dialyzer housing.
      Consequently, we developed the APS dialyzer APS-SA series, equipped with wave
      shaped hollow-fiber membrane bundles as an optimal three-dimensional morphology
      along with new housings, to realize enhanced dialysis performance. Incorporation
      of a new type of housing, including a full baffle structure and a short taper
      section, and a new type of morphology for the hollow-fiber membrane bundles have
      been verified to allow the dialysate to diffuse uniformly along the full baffle
      panel around the circumference and to fully permeate into the core of the hollow
      fiber bundle. As a result, the APS-SA series has been proved to have achieved
      enhanced diffusion performance and increased clearance of small molecule solutes
      such as urea and creatinine, compared with conventional dialyzers. This series is
      expected to provide increased Kt/V values and dialysate-saving performance in
      future clinical use.

PMID- 16998706
TI  - Prevalence of pannus formation after aortic valve replacement: clinical aspects
      and surgical management.
AB  - Pannus formation after aortic valve replacement is not common, but obstruction
      due to chronic pannus is one of the most serious complications of valve
      replacement. The causes of pannus formation are still unknown and effective
      preventive methods have not been fully elucidated. We reviewed our clinical
      experience of all patients who underwent reoperation for prosthetic aortic valve
      obstruction due to pannus formation between 1973 and 2004. We compared the
      initial 18-year period of surgery, when the Bjork-Shiley tilting-disk valve was
      used, and the subsequent 13-year period of surgery, when the St. Jude Medical
      valve was used. Seven of a total of 390 patients (1.8%) required reoperation for
      prosthetic aortic valve obstruction due to pannus formation. All seven patients
      were women; four patients underwent resection of the pannus and three patients
      needed replacement of the valve. The frequency of pannus formation in the early
      group was 2.4% (6/253), whereas it was 0.73% (1/137) in the late group (P <
      0.05). Pannus was localized at the minor orifice of the Bjork-Shiley valve in the
      early group and turbulent transvalvular blood flow was considered to be one of
      the important factors triggering its growth. We also consider that small
      bileaflet valves have the possibility of promoting pannus formation and that the
      implantation of a larger prosthesis can contribute to reducing the occurrence of
      pannus.

PMID- 16998707
TI  - The level of ganglion clipping for hyperhidrosis.

PMID- 16998709
TI  - A model for foramen ovale puncture training: technical note.

PMID- 16998712
TI  - Preconditioning and neurotrophins: a model for brain adaptation to seizures,
      ischemia and other stressful stimuli.
AB  - The amino acid glutamate, the major excitatory neurotransmitter in the central
      nervous system, activates receptors coupled to calcium influx. Excessive
      activation of glutamate receptors in conditions such as severe epileptic seizures
      or stroke can kill neurons in a process called excitotoxicity. However, subtoxic
      levels of activation of the N-methyl-D-aspartate (NMDA) type of glutamate
      receptor elicit adaptive responses in neurons that enhance their ability to
      withstand more severe stress. A variety of stimuli induce adaptive responses to
      protect neurons. For example, sublethal ischemic episodes or a mild epileptic
      insult can protect neurons in a process referred to as tolerance. The molecular
      mechanisms that protect neurons by these different stressful stimuli are largely
      unknown but they share common features such as the transcription factor, nuclear
      factor kappa B (NF-kappaB), which is activated by ischemic and epileptic
      preconditioning as well as exposure to subtoxic NMDA concentrations. In this
      article, we describe stress-induced neuroprotective mechanisms highlighting the
      role of brain-derived neurotrophic factor (BDNF), a protein that plays a crucial
      role in neuronal survival and maintenance, neurogenesis and learning and memory.

PMID- 16998713
TI  - Preparation of tritiated oostatic peptides for study of radioactivity
      incorporation in flesh fly Neobellieria bullata.
AB  - A series of insect oostatic peptides containing 3,4-dehydroproline in the C
      terminal part or inside of the peptide chain was synthesized and tritiated by
      addition of (3)H2 to double bond of 3,4-dehydroproline residue. (3)H-label was
      introduced also into tyrosine residue of oostatic tetra- and pentapeptides by
      isotopic exchange of benzyl beta-hydrogens. In this way, three types of tritiated
      peptides were prepared, different in the radiolabeled amino acid position: [(3)H]
      Tyr-Asp-Pro-Ala-OH, H-Tyr-Asp-[(3)H] Pro-Ala-OH, [(3)H] Tyr-Asp-Pro-Ala-Pro-OH, H
      Tyr-Asp-[(3)H] Pro-Ala-Pro-OH, H-Tyr-Asp-Pro-Ala-[(3)H] Pro-OH, H-Tyr-Asp-Pro-Ala
      Pro(5)-[(3)H] Pro-OH and H-Asp-[(3)H] Pro-OH. These peptides made possible a
      highly sensitive comparative study on radioactivity incorporation into head and
      ovaries of the flesh fly Neobellieria bullata, which revealed this process to
      proceed differently. The reasons of the found differences are discussed.

PMID- 16998714
TI  - Suppression of myofibrillar proteolysis in chick skeletal muscles by alpha
      ketoisocaproate.
AB  - We previously reported that L-leucine suppresses myofibrillar proteolysis in
      chick skeletal muscles. In the current study, we compared the effects of L- and D
      enantiomers of leucine on myofibrillar proteolysis in skeletal muscle of chicks.
      We also assessed whether leucine itself or its metabolite, alpha-ketoisocaproate
      (alpha-KIC), mediates the effects of leucine. Food-deprived (24 h) chicks were
      orally administered 225 mg/100 g body weight L-leucine, D-leucine or alpha-KIC
      and were sacrificed after 2 h. L-Leucine administration had an obvious inhibitory
      effect on myofibrillar proteolysis (plasma N(tau)-methylhistidine concentration)
      in chicks while D-leucine and alpha-KIC were much more effective. We also
      examined the expression of the proteolytic-related genes (ubiquitin, proteasome,
      m-calpain and cathepsin B) by real-time PCR of cDNA in chick skeletal muscles.
      Ubiquitin mRNA expression was decreased by D-leucine and alpha-KIC but not L
      leucine. Proteasome and m-calpain mRNA expressions as well as cathepsin B mRNA
      expression were likewise decreased by L-leucine, D-leucine and alpha-KIC. These
      results indicate that D-leucine and alpha-KIC suppress proteolytic-related genes,
      resulting in an decrease in myofibrillar proteolysis while L-leucine is much less
      effective in skeletal muscle of chicks, may be explain by conversion of D-leucine
      to alpha-KIC.

PMID- 16998715
TI  - Virtual screening for finding natural inhibitor against cathepsin-L for SARS
      therapy.
AB  - Recently Simmons et al. reported a new mechanism for SARS virus entry into target
      cells, where MDL28170 was identified as an efficient inhibitor of CTSL-meditated
      substrate cleavage with IC(50) of 2.5 nmol/l. Based on the molecule fingerprint
      searching method, 11 natural molecules were found in the Traditional Chinese
      Medicines Database (TCMD). Molecular simulation indicates that the MOL376 (a
      compound derived from a Chinese medicine herb with the therapeutic efficacy on
      the human body such as relieving cough, removing the phlegm, and relieving
      asthma) has not only the highest binding energy with the receptor but also the
      good match in geometric conformation. It was observed through docking studies
      that the van der Waals interactions made substantial contributions to the
      affinity, and that the receptor active pocket was too large for MDL21870 but more
      suitable for MOL736. Accordingly, MOL736 might possibly become a promising lead
      compound for CTSL inhibition for SARS therapy.

PMID- 16998716
TI  - Taurine release in mouse brain stem slices under cell-damaging conditions.
AB  - Taurine has been thought to be essential for the development and survival of
      neural cells and to protect them under cell-damaging conditions. In the brain
      stem taurine regulates many vital functions, including cardiovascular control and
      arterial blood pressure. We have recently characterized the release of taurine in
      the adult and developing brain stem under normal conditions. Now we studied the
      properties of preloaded [3H]taurine release under various cell-damaging
      conditions (hypoxia, hypoglycemia, ischemia, the presence of metabolic poisons
      and free radicals) in slices prepared from the mouse brain stem from developing
      (7-day-old) and young adult (3-month-old) mice, using a superfusion system.
      Taurine release was greatly enhanced under these cell-damaging conditions, the
      only exception being the presence of free radicals in both age groups. The
      ischemia-induced release was characterized to consist of both Ca2+-dependent and 
      independent components. Moreover, the release was mediated by Na+-, Cl--dependent
      transporters operating outwards, particularly in the immature brain stem. Cl-
      channel antagonists reduced the release at both ages, indicating that a part of
      the release occurs through ion channels, and protein kinase C appeared to be
      involved. The release was also modulated by cyclic GMP second messenger systems,
      since inhibitors of soluble guanylyl cyclase and phosphodiesterases suppressed
      ischemic taurine release. The inhibition of phospholipases also reduced taurine
      release at both ages. This ischemia-induced taurine release could constitute an
      important mechanism against excitotoxicity, protecting the brain stem under cell
      damaging conditions.

PMID- 16998717
TI  - Multiple sclerosis: pharmacogenomics and personalised drug treatment.
AB  - Multiple sclerosis (MS) is a disorder of the central nervous system with an
      inflammatory and a neurodegenerative component. We do not yet have a definitive
      therapy for MS. Attempts to develop new treatments are long and costly and should
      be paralleled by studies aimed at increasing the therapeutic index of the
      existing treatments, interferon beta and glatiramer acetate. Pharmacogenetics and
      pharmacogenomics may be of use in this respect though their application may not
      be straightforward, particularly in MS.

PMID- 16998718
TI  - Combination therapy.
AB  - So far, off-label recommendation of a combination therapy is mainly based on
      phase II study evidence and on largely accepted expert opinions. Combination
      therapy represents a new, more global strategy, to increase the possible benefits
      with the combined use of already available disease-modifying therapies or with
      other new agents, having an acceptable theoretical rationale and a good safety
      and efficacy profile. The therapeutic strategies of the near future will try to
      select among different and individualised combinations of drugs, with distinct
      mechanisms of action, and possibly with synergistic activity, to maximise
      benefits and minimise risks. The combination approach is at present particularly
      recommended for more aggressive forms of multiple sclerosis (MS) and for non
      responders to available drugs, although the theoretical rationale and accumulated
      experience would suggest its use in all MS patients right from the beginning of
      the disease.

PMID- 16998719
TI  - Is there or is there not a place for anti-interferon antibodies in the decision
      making of multiple sclerosis treatment optimisation?
AB  - Several factors contribute to the fact that not all multiple sclerosis (MS)
      patients respond equally well to long-term interferon beta (IFNbeta) treatment,
      even if the initial response is adequate. Among these factors, anti-interferon
      neutralising antibodies (NAbs) may be included. There is increasing evidence that
      these antibodies have a clinical impact in MS treated patients, which is evident
      some months following the initiation of treatment with IFN?. Several efforts to
      reduce the concentration of NAbs, especially when they are in high titres and
      clinically active, have failed. However, the same efforts may be more effective
      if applied following early detection of the antibodies, thus leading to a
      continuation of the initially selected interferon treatment.

PMID- 16998720
TI  - Italian Multiple Sclerosis Database Network.
AB  - The Multiple Sclerosis Database Network (MSDN) is the first Italian multiple
      sclerosis (MS) registry. The preliminary results on the MSDN cohort demonstrated
      that the risk of disability progression, in a sample of 2090 MS patients, was
      reduced by about four- to five-fold in patients exposed to IFNbeta for more than
      4 years compared with patients exposed for up to 2 years. More recent results
      showed, in a subset of 1170 relapsing-remitting MS patients, of whom 918 were
      treated with IFNbeta and 252 were untreated, that IFNbeta-treated patients had a
      differential reduction in EDSS score change of -0.055 for each year of follow-up
      in comparison with the untreated group. These results provide significant
      information on the effectiveness of IFNbeta treatment on long-term disability
      progression in MS.

PMID- 16998721
TI  - Methodology of clinical trials in multiple sclerosis.
AB  - The scope of the paper is to summarise key issues in methodology used in clinical
      trials on multiple sclerosis (MS) treatment and help clinicians to better
      understand articles reporting the results of these trials. Relapsing ratio and
      disability progression based on the Expanded Disability Status Scale are
      currently used as clinical efficacy primary outcomes, but more global
      measurements should be used in future such as the MS Functional Composite. For
      magnetic resonance imaging (MRI) outcomes, new MRI composites and indexes are
      already available (Z4 score, conventional MRI-derived end-points) that, together
      with new MRI techniques (magnetisation- transfer MRI and proton resonance
      spectroscopy), offer more precise neuroimaging assessments of the disease. These
      efficacy measurements should be presented in articles as number needed to treat,
      which assists the reader to calculate and compare the treatments' power and
      safety.

PMID- 16998722
TI  - Treatment of multiple sclerosis with interferon beta in clinical practice: 2-year
      follow-up data from the South Italy Mobile MRI Project.
AB  - This follow-up study assessed the 2-year clinical and magnetic resonance imaging
      (MRI) outcomes of patients with multiple sclerosis (MS) originally enrolled in an
      MRI study conducted at eight centres in south Italy (the South Italy Mobile MRI
      Project). Of the 597 MS patients recruited at baseline, 391 returned for the
      follow-up study. Of these, 363 provided 2-year clinical and MRI follow-up data,
      and 215 were still undergoing treatment with one of four interferon beta
      regimens: Avonex, 30 mcg intramuscularly once weekly; Betaferon, 250 mcg
      subcutaneously (sc) every other day; Rebif 22 mcg sc three times weekly (tiw;
      Rebif 22); or Rebif 44 mcg sc tiw (Rebif 44). Over the 2-year follow-up period,
      patients receiving the higher dose of Rebif were more likely to remain free from
      relapses [odds ratio (OR) = 2.23] and from developing both new T2 (OR = 0.15) and
      new T1 black hole lesions (OR = 0.22), when compared with patients in the Avonex
      group. Despite some limitations in the trial design, the results from this follow
      up study provide helpful clinical and MRI data on the efficacy of interferon beta
      regimens in MS patients treated in the clinical setting.

PMID- 16998723
TI  - Interferon after 10 years in patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a life-long disease that typically affects young
      adults. The introduction of disease-modifying therapy has changed the clinical
      and social burden of the disease. Safety, tolerability and efficacy profiles of
      Interferon beta (IFNbeta) therapy in MS have been widely highlighted both in
      trial settings and in daily clinical practice. However, there is a relative lack
      of information on the long-term period: all pivotal trials must be considered
      short-term in a disease with an average duration of 30-40 years and post
      marketing studies suffer from some limitations. Moreover, current available
      IFNbeta preparations are only partially effective and are difficult to
      administer, which has led to poor patient compliance. Over the treatment period,
      a problem could be the development of neutralising antibodies (NAbs) against the
      drug, which have been related to lessening treatment benefits. Despite these
      restrictions, IFNbeta still remains the first choice treatment in MS.

PMID- 16998724
TI  - Epilepsy and polycystic ovary syndrome: where is the link?
AB  - Several reports in the literature describe an increased prevalence of polycystic
      ovary syndrome (PCOS) in women with epilepsy. The possible pathogenesis of the
      association between epilepsy and PCOS is not clear yet, and different hypotheses
      have been proposed: while some authors suggest that epilepsy may affect the
      hypothalamic control of reproductive function, others propose a pathogenic role
      of the antiepileptic drug valproate. In this article we review the literature on
      the subject, and propose a pathogenic theory in which both epilepsy and valproate
      play different and significant roles in inducing reproductive endocrine
      disturbances in women with seizures.

PMID- 16998725
TI  - Fertility in patients with multiple sclerosis: current knowledge and future
      perspectives.
AB  - The issue of fertility in patients with multiple sclerosis (MS) has not been
      exhaustively studied. Epidemiological data have suggested that spontaneous
      fecundity might be reduced; several endocrine and sexual disturbances potentially
      interfering with reproduction have been evidenced in MS patients of both sexes.
      Moreover, some medical treatments used in MS (e. g., mitoxantrone,
      cyclophosphamide) may exert detrimental effects on spermatozoa as well as on
      oocytes, leading to early impairment of fertility. This review illustrates the
      factors potentially interfering with fertility in MS and discusses the
      therapeutic tools that may be used to promote fertility in these patients. The
      safety of hormonal therapies in MS is also examined. The current applications of
      assisted reproductive technology (ART) are discussed, including in vitro
      fertilisation (IVF) techniques. Currently available methods to preserve fertility
      in patients that undergo cytotoxic treatments by means of sperm/oocyte
      cryostorage or by ovarian fragment cryopreservation and autografting are
      considered.

PMID- 16998726
TI  - Functional rehabilitation and brain tumour patients. A review of outcome.
AB  - The increasing prevalence of brain tumours and longer duration of survival
      achieved by recent advances in treatment prompt a critical analysis of the impact
      of functional rehabilitation on patients with brain tumours. In this review brain
      tumours and outcome of brain tumour patients are discussed from a rehabilitation
      perspective, taking into account not only life expectancy but also the direct and
      indirect causes of functional impairment. Results of functional rehabilitation
      and factors involved in its effectiveness are presented and analysed to serve as
      a basis to neurologists involved in the management of patients with brain
      tumours.

PMID- 16998727
TI  - Expression of multidrug resistance type 1 gene (MDR1) P-glycoprotein in
      intractable epilepsy with different aetiologies: a double-labelling and electron
      microscopy study.
AB  - The objective of this study was to analyse the clinical characteristics,
      pathological features and expression patterns of multiple drug resistance type 1
      (MDR1) and glial fibrillary acidic protein (GFAP) in intractable epilepsy
      patients with variable aetiologies and to analyse the relationships between the
      clinical and pathological findings. Twenty-six patients (15 males, 11 females,
      age range 4-25 years, mean age 22.92 years, SD 11.19 years) with intractable
      epilepsy were included in this study; the clinical characteristics were
      considered, and the pathological changes as well as expression of MDR1 and GFAP
      in surgically removed brain tissues of each subject were examined under light and
      electron microscopy. All patients presented a long-lasting, refractory epilepsy,
      mostly of the partial type, due to different causes, such as trauma, vascular
      injuries, encephalitis, cortical dysplasia, cavernous angioma and Sturge-Weber
      disease. Neuronal degenerative damage, reactive proliferation of astrocytes, as
      well as overexpression of GFAP and MDR1, appeared as common pathological features
      in all cases. The detection of MDR1 by electron microscopy allowed us to
      precisely define its cellular location in reactive astrocytes and to exclude the
      presence of the antigen in other cellular types. In all cases, pathological
      features, at both light and electron microscopy, were similar, independent of the
      different clinical presentation and aetiology.

PMID- 16998728
TI  - Two novel Italian CADASIL families from Central Italy with mutation CGC-TGC at
      codon 1006 in the exon 19 Notch3 gene.
AB  - Here we describe clinical, neuropsychological and neuroradiological findings in 6
      subjects belonging to two unrelated Italian cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) kindreds
      from the same geographic area who shared a common Arg1006Cys mutation. Subjects
      from Family A were virtually asymptomatic, and yet showed MRI pathological
      findings and a cluster of sub-clinical neuropsychological defects mainly centred
      on the visuospatial domain; patients from Family B had presented several
      clinically relevant episodes and showed a general cognitive impairment compatible
      with the clinical picture of vascular dementia. The present clinical observations
      are consistent with the hypothesis of a geographical clustering for CADASIL, and
      highlight that sub-clinical cognitive impairment may help to identify this
      syndrome in families presenting with only migraine.

PMID- 16998729
TI  - Human T-cell lymphotropic virus type I (HTLV-I) confirmed by PCR-Southern blot
      and sequencing analysis in a woman with tropical spastic paraparesis.
AB  - Human T-cell lymphotropic virus type I (HTLV-I) is a human retrovirus and the
      aetiological agent of a progressive neurological disease called tropical spastic
      paraparesis/HTLV-I-associated myelopathy (TSP/HAM), as confirmed by evidence
      accumulated in HTLV-I seroprevalence studies. TSP/HAM is rarely diagnosed in
      Italy, given the low prevalence of HTLV-I in the population. TSP/HAM begins
      insidiously in the fourth decade, mainly with spastic paraparesis of the lower
      extremities and positive Babinski reflex, as well as interfering with bowel and
      bladder functions. In this study we report the clinical, virological and haemato
      chemical data of a 54-year-old woman, born in the Ivory Cost, with symptoms
      suggestive of TSP. The presence of HTLV-I infection was demonstrated by the
      detection of antibodies in serum and in cerebrospinal fluid by immunoenzymatic
      assay and Western blot analysis. In addition, viral isolation was carried out in
      peripheral blood cells, and the presence of HTLV-I proviral DNA was confirmed by
      polymerase chain reaction/Southern blot and sequencing analysis. According to our
      results, HTLV-I testing might be useful when TSP/HAM is suspected.

PMID- 16998730
TI  - Pravastatin in vivo reduces mononuclear cell migration through endothelial
      monolayers.
AB  - The objective was to evaluate pravastatin modulation on peripheral blood
      mononuclear cell (PBMC) migration across endothelial monolayers. Eleven
      hypercholesterolaemic patients were treated with pravastatin 20 mg/day. At
      baseline (T0), after 40 days (T40) and after 6 months (T 6 months) of treatment
      total serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein,
      triglycerides, C-reactive protein, as well as tumour necrosis factor-alpha (TNF
      alpha) and metalloproteinases-9 plasma levels were evaluated. At the same time
      points the effect of pravastatin on migration of PBMCs through a monolayer of
      murine brain endothelial cells was studied both in basal conditions and after
      endothelial stimulation with recombinant mouse TNF-alpha 10 ng/ml for 24 h. Seven
      volunteers were used as healthy controls. Significant decreases in total
      cholesterol, LDL and triglycerides as well as inhibition of transmigration were
      observed. PBMCs transmigration in patients prior to pravastatin therapy was
      higher than in healthy controls. These results suggest that pravastatin could be
      of benefit in a spectrum of diseases characterised by extravasation of PBMCs into
      the central nervous system.

PMID- 16998731
TI  - The end of the central dogma of neurobiology: stem cells and neurogenesis in
      adult CNS.
AB  - Until the 1990s, neurologists were practising their profession under the doctrine
      established in the late 19th to early 20th century by the prominent histologist
      Ramon y Cajal: "Once the development was ended, the founts of growth and
      regeneration of the axons and dendrites dried up irrevocably. In the adult
      centers, the nerve paths are something fixed, ended, and immutable. Everything
      may die, nothing may be regenerated. It is for the science of the future to
      change, if possible, this harsh decree." Similarly, Giulio Bizzozero, the most
      prominent Italian histologist and mentor of Camillo Golgi, classified the tissues
      of the human body into "labile, stable and perennial". Among the latter were the
      nerve cells, believed to be unable to proliferate in the postnatal brain. This
      classification was taught until a few years ago to generations of medical
      students and biologists all over the world. We have investigated the historical,
      methodological and technical reasons why this "central dogma of neurology", so
      influential in clinical and experimental neurology, has lasted so long. We
      examined how this dogma was broken and who contributed, and the difficulties
      encountered by the "heretical" researchers who contributed to this goal,
      especially between the 1960s and the early 1990s, when at last neurogenesis in
      the adult brain could no longer be denied. Finally, we propose that the
      understanding of the mechanisms underlying various neurological diseases and the
      interpretations of clinical syndromes, as well as the design of new therapies,
      are being revolutionised by the breaking of this dogma and the discovery of the
      presence of neural stem cells in the adult brain.

PMID- 16998732
TI  - The spectrum of mutations for the diagnosis of vanishing white matter disease.
AB  - Vanishing white matter disease (VWM; MIM #603896), also known as childhood ataxia
      with central nervous system hypomyelination (CACH) syndrome, is an autosomal
      recessive transmitted leukoencephalopathy related to mutations in each of the 5
      genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5) encoding for the 5 subunits of
      eukaryotic translation initiation factor 2B (eIF2B), essential for protein
      synthesis. VWM is characterised by ataxia, spasticity, variable optic atrophy and
      intermittent episodes of acute regression of clinical and neurological status.
      Another key step in diagnosis, besides clinical picture and gene sequencing, is
      magnetic resonance imaging (MRI), which typically shows a progressive rarefaction
      of the brain white matter, and its replacement by cerebrospinal fluid (CSF). In
      the present paper we summarise the up-to-date knowledge about VWM and include the
      full list of known mutations.

PMID- 16998733
TI  - Isolated bilateral anterior optic neuritis following chickenpox in an
      immunocompetent adult.
AB  - Chickenpox may lead to several different neurological complications, but optic
      neuritis has rarely been described; in particular, only one case of isolated
      bilateral anterior optic neuritis (AON) in an immune-competent adult has so far
      been reported. We describe a second case of this type and consider similarities
      and differences between our patient and all other cases of AON following
      chickenpox. Then, we discuss the therapeutic role of steroids and advance the
      hypothesis of different pathogenetic pathways in immune-competent and immune
      compromised subjects.

PMID- 16998734
TI  - Bilateral posterior medullary and cervical stroke: a case report.
AB  - Spinal strokes are often localised in the anterior spinal artery territory,
      whereas an involvement of the posterior spinal arteries (PSA) is uncommon, and
      usually unilateral. Bilateral PSA stroke is exceptional. A 70-year-old woman,
      after a mild head trauma, presented with cervical pain, left hypoaesthesia and
      sensitive ataxia, which then extended to the right hemibody, including face. A
      Doppler ultrasound showed an only systolic flow signal in the left vertebral
      artery (VA). MR showed a bilateral infarction extending from the posterior
      medulla oblongata to C4 and a left hypoplasic VA with lack of visualisation of
      the V3 segment. This case was peculiar, implying a bilateral stroke in the PSA
      territory, possibly related to a left VA dissection, and in the presence of a
      dominant PSA, originating from the hypoplasic VA and of hyposupply of posterior
      radiculomedullary arteries and anastomoses.

PMID- 16998735
TI  - Meningitis following relapsing painful ophthalmoplegia in aspergillus sphenoidal
      sinusitis: a case report.
AB  - We report the case of a 58-year-old woman in whom relapsing painful
      ophthalmoplegia related to a mycetoma of the sphenoid sinus gave origin to
      meningitis with markedly depressed glucose levels in the cerebrospinal fluid.
      Surgical exeresis of the mycetoma allowed aetiological diagnosis (aspergillosis)
      and--together with antimycotic therapy--led to durable clinical response.

PMID- 16998736
TI  - Isolated oculomotor nerve palsy as the presenting clinical manifestation of a
      meningeal carcinomatosis: a case report.
AB  - We present a previously unreported case of isolated oculomotor nerve palsy as the
      inaugural clinical sign of meningeal carcinomatosis (MC). Gadolinium-enhanced
      magnetic resonance images (MRI) were unremarkable. Cerebrospinal fluid (CSF)
      analysis showed malignant cells consistent with a pulmonary adenocarcinoma; the
      chest CT revealed a small pulmonary mass in the upper right lobe. This case
      highlights the importance of considering MC in all patients who develop sudden
      oculomotor palsy; lumbar punctures should always be performed on patients with
      normal MRI when other possible causes of oculomotor palsy have been ruled out.

PMID- 16998737
TI  - Spontaneous bilateral carotid artery dissection and hereditary haemochromatosis:
      what relationship?

PMID- 16998739
TI  - Diagnosis and management of a massive true inferobasal ventricular aneurysm ante
      perforationem.

PMID- 16998740
TI  - Mechanisms of regional wall motion abnormalities in contrast-enhanced dobutamine
      stress echocardiography.
AB  - BACKGROUND: In the diagnosis of coronary artery disease (CAD) with Dobutamine
      Stress Echocardiography (DSE), regional wall motion abnormalities (RWMA) are
      assumed to indicate a perfusion deficit. METHODS AND RESULTS: For a more
      particular examination of RWMAs, we compared simultaneous echo-contrast
      (Optisone)-enhanced DSE (0-40 microg/kg Dobutamine, 16-segment- model) and MiBi
      SPECT in a prospective double-blinded study design in 69 non-selected consecutive
      patients (44 male, 25 female, age 64+/-12 years). Additionally, all patients were
      examined by coronary-angiography. The prevalence of significant CAD (stenosis
      >50% lumen diameter) was 52%. DSE had a sensitivity of 78% and a specificity of
      66% for the detection of significant CAD with a positive and negative predictive
      value of 72 and 73%, respectively. Among 28 patients with significant CAD and
      positive DSE study (true positive), 78% displayed a corresponding perfusion
      deficit in MiBi-SPECT. Among 11 patients with a positive DSE study but no current
      significant coronary stenosis (false positive), 82% showed stress-induced RWMAs
      in the inferior/posterior region, 73% displayed left ventricular hypertrophy, 54%
      resting-ECG abnormalities and 45% resting-RWMA (3 previous MI, 2 previous CABG
      surgery). Among 8 patients with negative DSE study but significant coronary
      stenosis (false negative), 75% had a stenosis of the LCX, 63% displayed resting-
      WMA, 63% displayed left bundle branch block or ST-segment depression, 50%
      displayed only peripheral coronary stenosis, and DSE visualization was suboptimal
      in 38%. CONCLUSION: This prospective study in non-selected patients shows that
      the majority of RWMAs in DSE are matched to a perfusion deficit detectable by
      nuclear imaging. Nevertheless, pre-existing cardiac abnormalities may also lead
      to stress-induced RWMA not associated with a perfusion deficit or mask a
      perfusion deficit upon DSE. Particularly in patients with LV hypertrophy, resting
      RWMA, bundle branch block or ST segment depression, the predictive value of DSE
      may, therefore, be limited.

PMID- 16998741
TI  - Hypoxemia from right-to-left shunting through a patent foramen ovale in right
      ventricular infarction: treatment by revascularization, preload reduction, and,
      finally, interventional PFO closure.

PMID- 16998742
TI  - Aortic valve rupture after blunt chest trauma.

PMID- 16998743
TI  - Slow pathway ablation in a 5-year-old boy with atrioventricular septal defect:
      value of cryoenergy application.

PMID- 16998744
TI  - Catheter ablation of atrial fibrillation: ongoing atrial fibrillation inside a
      single pulmonary vein after successful electrical disconnection and restoration
      of sinus rhythm in both atria.

PMID- 16998745
TI  - Radiofrequency ablation of right ventricular outflow tract tachycardia using a
      magnetic resonance 3D model for interactive catheter guidance.

PMID- 16998746
TI  - Chest pain due to sternotomy wire suture in a patient with revascularized
      coronary heart disease.

PMID- 16998747
TI  - Abstracts of the 9th Congress of the German Society for Biological Psychiatry, 12
      14 October 2006, Munich, Germany.

PMID- 16998748
TI  - Intravenous immunoglobulins in neurological diseases.

PMID- 16998749
TI  - Basic principles of intravenous immunoglobulin (IVIg) treatment.
AB  - The original rationale for the therapeutic application of immunoglobulins was
      prevention and treatment of infectious diseases. With the description of
      agammaglobulinemia, substitution therapy became the primary indication for the
      use of immunoglobulins. Limitations and side effects of the intramuscular
      administration of immunoglobulins led to the development of preparations for
      intravenous use (IVIg). In the early 1980s an immunomodulatory effect of IVIg was
      described. Since then, the efficacy of IVIg has been established in controlled
      trials for diseases like idiopathic thrombocytopenic purpura, Kawasaki disease,
      Guillain-Barre syndrome, dermatomyositis, and many others. There is a large body
      of evidence that IVIg can modulate an immune reaction at the level of T cells, B
      cells, and macrophages, interferes with antibody production and degradation,
      modulates the complement cascade, and has effects on the cytokine network.
      However, the precise mechanism of action is not yet clear.

PMID- 16998750
TI  - Epidemiology of neuroimmunological diseases.
AB  - This review gives an overview of various neuroimmunological diseases in terms of
      incidence and prevalence rates, age and sex distribution, and the frequency of
      subtypes, if applicable. The disorders selected for review are inflammatory
      muscle disorders (polymyositis, dermatomyositis and inclusion body myositis),
      myasthenia gravis, immune-mediated polyneuropathies (Guillain-Barre syndrome,
      chronic polyneuritis and vasculitic neuropathies), and multiple sclerosis.

PMID- 16998751
TI  - Role of IVIg in autoimmune, neuroinflammatory and neurodegenerative disorders of
      the central nervous system: present and future prospects.
AB  - INTRODUCTION: Although IVIg is highly effective in several autoimmune
      neuromuscular disorders (neuropathies, myopathies and neuromuscular junction
      disorders), its effectiveness in autoimmune or neuroinflammatory CNS diseases,
      with the exception of multiple sclerosis, has not been explored. Emerging data
      suggest that IVIg may have a role not only in certain antibody-mediated CNS
      diseases but also in some neurodegenerative disorders associated with
      "neuroinflammation" mediated by proinflammatory cytokines. METHODS: Data from a
      previously reported controlled study conducted in patients with stiff person
      syndrome (SPS) are presented as a paradigm of a CNS disorder associated with
      specific autoantibodies responding to IVIg. Emerging data using IVIg in various
      neuroinflammatory and neurodegenerative conditions such as Alzheimers disease,
      postpolio syndrome (PPS), fibrotic disorders, chronic painful conditions and
      narcoplepsy are summarized. RESULTS: On the basis of a double-blind placebo
      controlled trial conducted in SPS patients with high anti-GAD antibodies, IVIg
      was shown to be effective resulting in improvement of stiffness and heightened
      sensitivity scores and increasing the patients' ability to carry out daily
      activities. In SPS, IVIg also suppressed the anti-GAD antibodies titers probably
      via an anti-idiotypic effect. A controlled study in patients with PPS, showed
      reduction in cytokines in serum and CSF with concomitant improvement in the
      patients' strength and ability to carry out their daily activities. The effect of
      IVIg in a small number of patients with Alzheimer's disease was promising by
      reducing the ADAS-cog scores, suggesting a reversal of disease progression. IVIg
      has been shown to have an effect on tissue fibrosis and in certain subacute
      painful conditions by suppressing cytokines that mediate fibrosis or pain. In
      another uncontrolled study, IVIg reduced the number of cataplectic attacks in
      narcolepsy patients. CONCLUSIONS: IVIg is effective in anti-GAD-positive patients
      with SPS. Whether it is also effective in other GAD-positive CNS disorders such
      as epilepsies, cerebellar degenerations or Batten's disease need to be studied in
      control trials. Emerging data suggest that IVIg, by suppressing proinflammatory
      cytokines, may exert a beneficial effect in patients with Alzheimer's disease,
      postpolio syndrome, chronic pain syndromes, fibrotic disorders and narcolepsy.
      Controlled studies are being planned or conducted to substantiate the benefit of
      IVIg in neurodegenerative disorders.

PMID- 16998752
TI  - Intravenous immunoglobulin therapy in paraneoplastic neurological syndromes.
AB  - Combining clinical and immunological information, a neurological syndrome can now
      be diagnosed as a "definite" or "possible" paraneoplastic syndrome according to
      the newly suggested diagnostic criteria of the PNS Euronetwork. Differentiated
      diagnosis of a paraneoplastic syndrome is essential for differential therapy in
      patients. According to the response to IVIG therapy, paraneoplastic disorders may
      be subgrouped in group A, a clinical response is the rule (prototype Lambert
      Eaton myasthenic syndrome), and in group B, IVIG may be helpful in single
      patients and is indicated in specific clinical settings (prototype anti-Hu
      associated neurological syndromes). The mode of action of IVIG may range from
      direct anti-idiotype effect to indirect effects on the cellular part of the
      pathogenesis of paraneoplastic syndromes. Due to the therapeutic relevance, it is
      therefore important to diagnose a PND as early as possible, and start
      immunotherapy including IVIG immediately.

PMID- 16998753
TI  - Intravenous immunoglobulin treatment in vasculitis and connective tissue
      disorders.
AB  - Vasculitis syndromes and connective tissue disorders are heterogeneous and mostly
      rare multisystem disorders with various autoimmune mechanisms driving tissue
      inflammation and remodeling, ischemic and hemorrhagic tissue damage. While the
      nervous system can be affected by most of these diseases, the pathogenesis for
      neural involvement is often ambiguous and elusive for the clinician. Intravenous
      immunoglobulins (IVIG) have been used for the treatment of most of these
      disorders. However, a thorough review of the literature indicates that the role
      for IVIG has to be discussed for individual entities, has often only anecdotal
      evidence, and is particularly hard to define with respect to neurological
      manifestations. This review gathers the available evidence on the efficacy of
      IVIG in neurologically relevant rheumatic diseases, leading to recommendations
      for their clinical use.

PMID- 16998754
TI  - Intravenous immunoglobulins as therapeutic option in the treatment of multiple
      sclerosis.
AB  - Treatment of neurological disorders with intravenous immunoglobulin (IVIG) is an
      increasing feature of practice for an expanding range of indications. This
      article reviews the current literature regarding the role of IVIG treatment in
      multiple sclerosis (MS) and summarizes recommendations for the use of IVIG in
      different courses and clinical subsets of the disease. Principally based on the
      results of four randomized, double-blind, placebo-controlled trials (RCTs) and a
      corresponding meta-analysis, the amount of evidence for the efficacy of IVIG
      treatment is currently most convincing for the relapsing-remitting course of MS
      (RRMS); nevertheless, it lags clearly behind that for beta interferon due to
      smaller study sizes, partial deficits in study design and not established optimal
      dosage. This prompted the basis for a consensus statement in some countries to
      recommend IVIG as second-line treatment in RRMS, when other licensed therapies
      (i. e., beta interferon, glatiramer acetate) are individually not tolerated due
      to side effects or concomitant disease. Recent evidence indicates that IVIG is
      also effective in clinically isolated syndrome (CIS) and should be considered as
      a therapeutic option, particularly when licensed immunotherapy can not be
      offered. During an acute relapse additional IVIG administration to established
      steroid treatment showed no benefit. Despite promising experimental data on
      promotion of remyelination, fixed chronic deficits were not reversed or improved
      by long-term IVIG treatment either. Currently there is no indication for IVIG
      treatment in the chronic progressive disease stages, since a large and well
      designed RCT failed to show any beneficial effect in patients with secondary
      progressive MS (SPMS) and data derived from primary progressive MS (PPMS) are
      still pending. However, preliminary results of a so far unpublished RCT including
      patients with PPMS and SPMS suggest a strong trend towards a beneficial effect in
      PPMS. So far, IVIG is the only therapy investigated for reducing postpartum
      relapses, whereas immunomodulatory drugs are contraindicated during pregnancy and
      lactation period. Data evaluating the peripartal use of IVIG along with the
      positive results of the trials in RRMS justify postpartal IVIG treatment
      particularly for mothers, who choose to breastfeed, under consideration of the
      recommendations specified for the relapsing-remitting disease course. As recently
      shown IVIG administration right from the early weeks of pregnancy appears to be a
      promising strategy, but cannot be recommended from the viewpoint of evidence
      based medicine.

PMID- 16998755
TI  - Therapy of immune neuropathies with intravenous immunoglobulins.
AB  - Autoimmune-mediated disorders belong to the main causes of neuropathies
      worldwide. During recent years much progress has been achieved in the
      understanding of the underlying pathomechanisms, associated with implications for
      therapeutic approaches. Here we will briefly review the pathogenesis and discuss
      treatment options of the Guillain-Barre syndrome, chronic inflammatory
      demyelinating polyneuropathy, multifocal motor neuropathy, and neuropathies
      associated with paraproteinemias. In most of these disease entities intravenous
      immunoglobulins play a major role as effective and safe treatment options.

PMID- 16998756
TI  - Therapeutic options in autoimmune inflammatory myopathies (dermatomyositis,
      polymyositis, inclusion body myositis).
AB  - Polymyositis, dermatomyositis, and inclusion body myositis are idiopathic
      inflammatory myopathies of unknown etiology with autoimmune pathogenesis. For
      choosing an individual and efficient therapy, diagnostic assignment is an
      important factor. Therapeutic options in dermatomyositis and polymyositis include
      corticosteroids and immunosuppressives. Intravenous immunoglobulins are only
      needed in special cases. In inclusion body myositis, corticosteroids and
      immunosuppressives are not successful. At the moment intravenous immunoglobulins
      are the only therapeutic possibility.

PMID- 16998757
TI  - Rare indications of IVIG therapy in neurological diseases based on case reports
      and small studies.
AB  - IVIG treatment has been tried in several neurological diseases with presumed
      immunopathogenesis. Many of the rare neurological diseases seem to benefit from
      IVIG treatment; however, negative results have been rarely published. Despite the
      majority of positive results, a general use of IVIG cannot be recommended for
      these diseases. Beside the lack of controlled studies and the small numbers of
      reported cases, a publication bias has to be considered since negative study
      results are usually not reported. Therefore, at this stage treatment with IVIG
      should be used in conjunction with controlled therapy trials.

PMID- 16998758
TI  - Intravenous immunoglobulin therapy in neurological diseases during pregnancy.
AB  - Immunological changes during pregnancy influence the course of neurological
      autoimmune diseases in different ways. In case of pregnancy immunomodulatory
      standard therapies such as interferon-beta, glatiramer acetate,monoclonal
      antibodies and cytostatics mostly should be discontinued. In those cases
      intravenous immunoglobulin (IVIg) therapy might be an alternative. In some
      diseases, contemporary publications describe positive therapeutic effects on the
      course of disease during or after pregnancy.

PMID- 16998759
TI  - Adverse effects of treatment with intravenous immunoglobulins for neurological
      diseases.
AB  - Therapy with intravenous immunoglobulins (IVIg) is considered to be a safe
      treatment for a number of immune-mediated neurological diseases. Published data
      about prevalence of adverse effects range from 11 to 81%. The purpose of our
      study was to preserve a representative view on adverse effects by analysis of a
      large cohort of patients treated by IVIg. A recent prospective study reported
      42.7% adverse events. The majority of patients presented with minor adverse
      effects, mostly asymptomatic laboratory changes. Rash or mild headache occurred
      especially when IVIg was administered with an infusion flow higher than 10 g/h.
      Severe complications like deep vein thrombosis or others are rare. In addition to
      its efficacy, IVIg therapy appears to be a safe therapy in immune-mediated
      neurological diseases. Most patients show no or minor adverse effects. Patients
      with pre-existent disorders like heart or renal insufficiency or immobilized
      patients, however, may be at higher risk for complications.

PMID- 16998760
TI  - IVIG therapy in neurological disorders of childhood.
AB  - There is growing evidence that intravenous immunoglobulins (IVIG) are effective
      in some neuroimmunological disorders of childhood. This short review summarizes
      the evidence-based indications and recommendations of IVIG therapy in these
      disorders. Despite considerable efforts to define the role and mechanisms of
      IVIG, more clinical studies are needed to further explore the therapeutic
      potential of IVIG in childhood diseases of the nervous system and muscle.

PMID- 16998761
TI  - Socio-economic aspects of neuroimmunological diseases.
AB  - Neuroimmunological diseases often have a chronic course and a high socio-economic
      impact, as most of them occur in younger patients and result in progressing
      disability and loss of work force. Although for many conditions different
      treatment strategies are available no sufficient data exist to give a reasonable
      account on the cost effectiveness of individual therapies. Treatment decision
      should primarily be guided by evidence from high quality clinical studies and-if
      available-from direct head-to-head trials and cost-effectiveness analysis.

PMID- 16998762
TI  - Immunoglobulins--basic considerations.
AB  - Immunoglobulins (Igs) or antibodies (Abs) are the principal operators of the
      adaptive humoral immune response. For optimum functional activity they acquire an
      optimized structure for antigen (Ag) recognition, precipitation, agglutination,
      phagocytosis (IgG1/3 and IgA), cytotoxicity (IgG1/3), transport through mucosa
      (IgA and IgM) and placenta (IgG1/3), complement activation (IgG1/3 and IgM) and
      release of inflammatory mediators (IgE). A diversity with potentially up to
      10(15) different Ab specificities is generated during Ag-independent B cell
      development in the bone marrow by combinatorial V-D-J joining, creation of
      junctional diversity, and combinatorial association of L and H chains.
      Furthermore,Ab variety is created during Ag-dependent B cell maturation in
      peripheral lymphatic tissues by isotype class switching and somatic
      hypermutation. Two types of enzymes play a key role in Ab diverseness, i. e., the
      products of recombination-activating genes RAG1 and RAG2 and the affinity induced
      deaminase (AID). The prevailing adult-type B2 cells provide the basis for the
      acquired humoral immune response characterized by Ab production,Ag processing and
      presentation, immunological memory and tolerance along with the generation of the
      anti-idiotype network,whereas the fetal-type B1 cells may play a role in innate
      immunity and autoimmunity. Impairment of B cell immunity includes
      immunodeficiency (agammaglobulinemia), malignant transformation (leukemia,
      lymphoma, plasmocytoma) and immune dysregulation (allergy, autoimmunity). The
      diagnostic relevance of Abs comprises classical serology (immunoprecipitation,
      agglutination, complement binding, RIA, ELISA), immunocytochemistry and
      immunohistochemistry, immunofluorescence (microscopic and flow cytometric),
      cytotoxicity tests, immunoblots, immunospot assays and immunoabsorption (affinity
      chromatography). Therapeutic application of Abs (passive immunization) is
      directed against infections, intoxications, solid tumors, leukemias and
      lymphomas, graft rejection and graft-versus-host reaction, hemolytic anemia, and
      autoimmune diseases. The generation of genetically engineered monoclonal Abs
      (mAbs) has revolutionized the diagnostic and therapeutic potential of Abs in
      almost all disciplines of modern medicine.

PMID- 16998763
TI  - [Training in sports medicine for medical students--Evaluation of a practice
      oriented teaching concept].
AB  - INTRODUCTION: Education in Sports Medicine is offered heterogeneously in German
      medical schools. Efficacy and acceptance among medical students are unknown. The
      self-image of sports has changed from a traditional, competition-oriented way to
      adventure, entertainment, wellness and health. Therefore changes of our curricula
      to a practical oriented way of teaching are required. In this regard a new
      curriculum was developed. The main focus, besides an interdisciplinary class in
      sports medicine was to offer practical education in sports to the students.
      METHODS: Efficacy and acceptance of the class were evaluated using a
      questionnaire. 90 medical students (58 male, 32 female) were included into the
      study . RESULTS: The interdisciplinary topics of the class were graded
      positively. Most of the presentations were regarded as very useful for the future
      practice. Empathy and commitment of the professor were keystones to good scores.
      The "fun-factor" was the key for the success of the practical assignment.
      Practical training was regarded as fundamental for a sports medicine class.
      DISCUSSION: Evaluation of the new concept as well as a discussion of the current
      practice to teach sports medicine at medical school confirm the need of a more
      practical oriented education, in order to meet the requirements of sports
      medicine in a time with changing self image of sports.

PMID- 16998764
TI  - [A comparison of orthopaedic sports medicine education in Germany and the US].
AB  - INTRODUCTION: The international exchange of German doctors especially in the US
      makes it important to compare both educational systems. The goal of this article
      is to discuss the differences and similarities between the German and US American
      curricula for Orthopaedic Sports Medicine. METHODS: The German and US American
      curricula for Sports Medicine and their education and fellowship programs were
      compared. RESULTS: The title 'Specialist for Sports Medicine' can be obtained in
      both countries. In Germany the curriculum is not speciality specific but offers a
      general Sports Medicine education that can be obtained through courses or
      fellowships. In the US this title can be obtained in two different ways, either
      through the American Board of Family Medicine (ABFM), or the American Board of
      Orthopaedic Surgery (ABOS) and their respective fellowship programs. DISCUSSION:
      The Sports Medicine curriculum in Germany and in the US is different with a
      general Sports Medicine program in Germany and a specific Sports Orthopaedic
      program in the US.

PMID- 16998766
TI  - [Dynamic ultrasound examination of the shoulder of golf players].
AB  - Although golf is becoming popular it can result in injury, usually from overuse
      and from poor technique. The shoulder is a commonly affected site, with the lead
      shoulder (or the left shoulder in the right-handed golfer) vulnerable to injury.
      With this study we tried to figure out any hyperlaxity of the lead shoulder using
      ultrasonography. 33 golf-players were investigated by questionnaire, clinical
      examination and dynamic ultrasonography. Neither clinically nor by using
      ultrasonography hyperlaxity of the shoulder was found. Nevertheless hyperlaxity
      followed by secondary impingement should be considered.

PMID- 16998765
TI  - [Golf with total joint replacement of the hip and knee].
AB  - Playing golf after THR and TKR is discussed controversially by orthopedic
      surgeons and Data of 16 patients receiving 22 THR (18 m/4f, 12 r/10 l) and of 11
      patients receiving 12 TKR (9 m/3f, 6 r/6 l) were analysed using a questionnaire.
      The mean age of THR-/TKR-sportsmen was 65,7 (58 - 78)/67,8 (61-76) years. In THR
      /TKR-patients surgery was done 59 (12-226)/39 (12-105) month ago. The best
      handicap (hcp) in their carrier/one year before/one year after surgery was in THR
      15,7 (2-36)/18,5 (6-36)/17,7 (4-36), in TKR 18,4 (6-24)/22,1 (8-34)/20,3 (8-28).
      11/7 sportsmen with THR/TKR could preserve the level of hcp following surgery, in
      7/0 hcp became worse and in 4/5 hcp was even better. Patients with 21 THR and 12
      TKR had less pain while playing golf in the operated joint one year after
      compared to one year before surgery, 1 patient with THR suffered more pain.
      During follow-up 13 THR/10 TKR reported of no problems playing golf, 7 THR/2 TKR
      had moderate pain, 2 THR/0 TKR had severe pain, no patients was unable playing
      golf following the joint replacement. Golf can be recommended as sporting
      activity after successful THR and TKR.

PMID- 16998767
TI  - [Nordic pole walking injuries--nordic walking thumb as novel injury entity].
AB  - BACKGROUND: Nordic pole Walking (NW) as trend sport is associated with beneficial
      effects on the cardiovascular system. Data regarding the injury and overload
      injury rates are pending. METHODS: 137 athletes (74 % females, 53 +/- 12 years,
      weight 73 +/- 13 kg, height 169 +/- 11 cm) were prospectively ask using a two
      sided questionnaire. Mean NW experience was 212.8 weeks with 2.9 +/- 1.8
      hours/week. The overall exposure was 29 160 h. RESULTS: NW injury rate was
      0.926/1000 h. Falls were evident in 0.24/1000 h. The upper extremity was involved
      more frequently (0.549/1000 h) than the lower extremity (0.344/1000 h). The most
      severe injury was a concomitant shoulder dislocation and luxation of the proximal
      interphalangeal joint of the index finger after a fall. The most frequent injury
      in NW was a distorsion of the ulnar collateral ligament of the thumb (0.206/1000
      h) after fall. Shoulder injuries account for 0.171/1000 h with 0.069/1000 h
      shoulder dislocations. Distal radius fractures were rare as ankle sprains and
      shinspints (0.034/1000 h). Muscle injuries were encountered only at the
      gastrocnemius muscle (0.137/1000 h). No knee ligament injuries were noted. In 5%,
      NW injuries caused interruption of the performance, with all patients returning
      to sport within 4 weeks on the same level as before. DISCUSSION: Nordic Walking
      is safe. Most frequently, a Nordic walking thumb is encountered during a fall
      with the athlete holding on to the NW pole until the very last moment before the
      hand hits the ground with the pole handle as hypomochlium that forces the thumb
      into abduction and extension. Modifications of the grip construction as well as
      information of the athlete and behaviour changes may be preventive measures.

PMID- 16998768
TI  - [The use of sonography in muscular injuries of the lower leg].
AB  - BACKGROUND: Over one third of all sports related injuries affect the muscle
      tendon apparatus. Therefore an easy, quick and cost effective method for
      diagnosis and follow up is necessary. METHODS: We studied 50 patients with muscle
      strain injuries divided in two groups. The patients of group A received an
      elastic bandage, within the next 24 hours the first sonography of the affected
      limb was performed. The next check up was after 7 to 14 days and after 4 to 6
      weeks. The average duration of use was registered. The visual analogue scale
      (VAS) was used to register pain, and the reduction of activity and motion was
      classified in three grades. In the patients of group B a tape bandage was applied
      to the injured leg. The same schedule was used for these patients. In all
      patients a cooling therapy was started as soon as possible. The two groups of
      patients were checked regularly using ultrasonography and compared to each other
      due to the different parameter. RESULTS: In 36 patients a muscular injury was
      detected sonographically during the first check up. In 13 patients on day 7 to
      14, still a lesion was detectable. And in one patient 6 weeks after injury a
      lesion was still detectable. The 37 patients of group A reported an average of
      6.9 points on VAS on day one, after 7 to 14 days 3.3 points and 0.8 points after
      the last check up. The 13 patients of group B reported an average of 6.7 points
      on VAS on day one, after 7 to 14 days 3.8 points and 2.0 points after the last
      check up. CONCLUSIONS: The clinical symptoms show good correlation to the
      sonographic results.

PMID- 16998769
TI  - [Prevention of deep vein thrombosis in total knee replacement--current status of
      therapy in orthopedie and trauma departments in Germany].
AB  - INTRODUCTION: Symptomatic deep vein thrombosis is a serious complication after
      total knee arthroplasty, with a risk of about 4-5% despite prevention with
      herparin. Aim of the current study was to find out about the actual status of
      thrombosis prophylaxis in Germany after total knee replacement. MATERIAL AND
      METHODS: In a countrywide survey 470 German trauma and orthopaedic surgery
      departments were asked about their prophylactic procedures addressing deep vein
      thrombosis after total knee replacement. RESULTS: 98% perform prevention of
      thrombosis with low-molecular-weight heparin, 2% use unfractioned heparin. Low
      molecular-weight heparin is applicated in standard doses in 48% and in 44%
      according to patient's weight. In 82% the prophylaxis is begun the night before
      surgery. The therapy is carried out for 4.7 weeks in mean. 96% use graduated
      compressions stocking as additional therapeutic option. CONCLUSION: Our survey
      shows that most of the surgeons perform prevention of deep vein thrombosis
      according to the official guidelines.

PMID- 16998770
TI  - The evidence for the elimination of rubella and congenital rubella syndrome in
      the United States: a public health achievement.

PMID- 16998771
TI  - The epidemiological profile of rubella and congenital rubella syndrome in the
      United States, 1998-2004: the evidence for absence of endemic transmission.
AB  - In 1969, the United States established its national rubella vaccination program.
      With the success of the program, 32 years later, reports of rubella reached
      record low numbers. To assess the achievement of elimination of rubella and
      congenital rubella syndrome (CRS) in the United States, 7 epidemiological
      criteria were used. Rubella cases reported to the National Notifiable Diseases
      Surveillance System from 1998 through 2004 and CRS cases reported to the National
      Congenital Rubella Syndrome Registry from 1998 through 2004 were analyzed. During
      1998-2000, the median number of reported rubella cases was 272, whereas, during
      2001-2004, the median number reported was 13. The incidence of rubella decreased
      significantly, from 0.1/100,000 population in 1998 to 0.005/100,000 population in
      2004. Since 2001, 5 infants with CRS have been reported--3 were born in 2001, 1
      was born in 2003, and 1 was born in 2004. The epidemiological evidence strongly
      supports the claim that rubella is no longer endemic in the United States. To
      prevent future rubella outbreaks and CRS cases, current strategies must be
      maintained.

PMID- 16998772
TI  - Genetic analysis of rubella viruses found in the United States between 1966 and
      2004: evidence that indigenous rubella viruses have been eliminated.
AB  - Wild-type rubella viruses are genetically classified into 2 clades and 10
      intraclade genotypes, of which 3 are provisional. The genotypes of 118 viruses
      from the United States were determined by sequencing part of the E1 coding region
      of these viruses and comparing the resulting sequences with reference sequences
      for each genotype, using the Bayesian inference program MRBAYES. Three genotypes
      of rubella viruses were found in the United States too infrequently to be
      considered for indigenous transmission. A fourth genotype was found frequently
      until 1981, and a fifth genotype was found frequently until 1988, but neither was
      obtained from nonimported cases after 1988. A sixth genotype was found frequently
      during 1996-2000, likely because of multiple importations from neighboring
      countries. The results of the present genetic analysis of rubella viruses found
      in the United States are consistent with elimination of indigenous viruses by
      2001, the year when rubella was considered to be eliminated on the basis of
      epidemiological evidence.

PMID- 16998773
TI  - Has the United States population been adequately vaccinated to achieve rubella
      elimination?
AB  - Mathematical models indicate that elimination of rubella virus transmission
      requires maintenance of approximately 90% rubella immunity among children. To
      evaluate whether rubella vaccination coverage among US preschool and school-age
      children is at levels consistent with rubella elimination, we reviewed data from
      3 sources: (1) the Biologics Surveillance, which documents the net number of
      vaccine doses sold (1970-2004); (2) state immunization surveys of school entrants
      5-6 years of age (1980-2005); and (3) the National Immunization Survey of
      children 19-35 months of age (1995-2004). Vaccine biologics data show that the
      net number of rubella vaccine doses sold was at least equivalent to the number of
      children born each year during 1970-2004. The average coverage for school-entrant
      surveys among reporting states was >95% for 1980-2004. National coverage among
      children 19-35 months of age was > or =90% overall for each year during 1995
      2004. Three independent surveys suggest that childhood coverage with rubella
      containing vaccine has been at sufficiently high levels to achieve elimination of
      rubella virus transmission.

PMID- 16998774
TI  - Rubella immunity levels in the United States population: has the threshold of
      viral elimination been reached?
AB  - After the 1989-1991 rubella resurgence, rubella vaccination efforts targeted
      children and women of childbearing age. Utilizing National Health and Nutrition
      Examination Survey data collected during 1988-1994 and 1999-2004, we assessed
      whether US levels of rubella seropositivity are consistent with rubella
      elimination and whether changes are consistent with immunization efforts. Serum
      samples with rubella antibody levels > or =10 IU tested by rubella immunoglobulin
      G enzyme immunoassay were considered to be positive. In 1999-2004, the overall
      age-adjusted rubella seropositivity level was 91.3% (95% confidence interval
      [CI], 90.5%-92.1%), a significant increase from 88.1% (95% CI, 86.9%-89.1%) in
      1988-1994 (P<.001). Among children, seropositivity was highest in children 6-11
      years of age (96.2%), followed by adolescents 12-19 years of age (93.7%). Both
      groups showed significant increases in immunity levels, in comparison with those
      in 1988-1994 (P<.001). Among adults, seropositivity among women increased (from
      88.9% to 91.5%; P=.015), and there was no change among men (from 87.8% to 88.0%;
      P=.84). In 1999-2004, population rubella immunity levels were at or above the
      modeled threshold for elimination of rubella virus transmission. Increases in
      immunity levels are consistent with vaccination efforts.

PMID- 16998775
TI  - Adequacy of surveillance to detect endemic rubella transmission in the United
      States.
AB  - BACKGROUND: Reported rubella cases in the United States are at the lowest numbers
      since the introduction of vaccine, suggesting that endemic transmission may have
      been interrupted. It is necessary to validate that the observed absence of
      rubella is due to the disappearance of disease rather than a failure of rubella
      surveillance. METHODS: Adequate rubella surveillance to detect ongoing
      transmission is characterized by evidence that rubella investigations are being
      conducted, detection of importations, and lack of spread from confirmed cases. We
      reviewed rubella surveillance data and activities from 5 sources: (1) data
      reported to the national surveillance system; (2) a survey of health departments
      and public health laboratories, including questions regarding any links between
      measles and rubella surveillance; (3) enhanced rubella surveillance activities in
      California and in New York City; (4) sentinel surveillance along the US-Mexico
      border; and (5) case detection in 8 large health maintenance organizations
      (HMOs). RESULTS: During 2002-2004, 35 cases of rubella were reported to the
      national system, including 12 (34%) imported cases. The 39 programs that
      responded to our survey reported conducting 1482 investigations for rubella;
      according to another national survey, 1921 investigations were conducted for
      measles. Forty-one laboratories responded to our survey and reported conducting
      6428 tests for acute rubella. No previously undetected (or unreported) cases of
      rubella or congenital rubella syndrome were identified by our survey or reviews
      of surveillance in California, New York, and along the US-Mexico border, and no
      additional cases were detected in the HMO database. CONCLUSIONS: No previously
      unrecognized spread cases or outbreaks of rubella were detected. Surveillance in
      the United States is sufficiently sensitive to identify indigenous cases of
      rubella, if they were occurring, supporting the contention that rubella has been
      eliminated from the United States.

PMID- 16998776
TI  - Efforts at rubella elimination in the United States: the impact of hemispheric
      rubella control.
AB  - We examined rubella vaccination trends, rubella surveillance, and disease
      patterns for the Americas, Mexico, and the United States, to evaluate the impact
      of hemispheric rubella control on rubella elimination in the United States during
      1997-2004. In 1997, 130,375 rubella cases were reported in the Americas, with
      38,042 reported in Mexico. Over the next 7 years, a rubella control initiative
      resulted in the administration of approximately 110 million rubella-containing
      vaccine doses in Latin America, with 77.7 million doses administered within
      Mexico. By 2004, the number of reported rubella cases had declined to 3103 in the
      Americas and 698 in Mexico. Concurrently, the number of rubella cases in the
      United States fell from 817 during 1997-1999 to <25 cases/year from 2001 onward,
      with loss of seasonality and geographic clustering, despite no change in
      vaccination rates. Implementation of rubella control strategies in the Americas,
      particularly in Mexico, appears to have facilitated rubella elimination in the
      United States.

PMID- 16998777
TI  - The history of rubella and rubella vaccination leading to elimination.
AB  - Congenital rubella syndrome (CRS) was discovered in the 1940s, rubella virus was
      isolated in the early 1960s, and rubella vaccines became available by the end of
      the same decade. Systematic vaccination against rubella, usually in combination
      with measles, has eliminated both the congenital and acquired infection from some
      developed countries, most recently the United States, as is confirmed by the
      articles in this supplement. The present article summarizes the clinical syndrome
      of CRS, the process by which the vaccine was developed, and the history leading
      up to elimination, as well as the possible extension of elimination on a wider
      scale.

PMID- 16998778
TI  - Diagnoses and vascular risk factors in a cohort of 150 attendees at a Memory
      Clinic.

PMID- 16998779
TI  - The effects of preferred music on agitation of older people with dementia in
      Taiwan.

PMID- 16998780
TI  - The relationship between generalized anxiety disorder, depression and mortality
      in old age.
AB  - BACKGROUND: The association between depression and an increased risk of death in
      elderly persons has been established in both clinical and community studies. Co
      occurrence of depression and generalized anxiety has been shown to represent more
      severe and more chronic psychopathology. However, little is known about the
      relation between generalized anxiety disorder, mixed anxiety-depression
      (generalized anxiety disorder and depression) and excess mortality in the
      elderly. OBJECTIVE: To investigate whether generalized anxiety and mixed anxiety
      depression are associated with mortality. METHOD: Generalized anxiety disorder,
      mixed anxiety-depression and depression were assessed in 4051 older persons with
      a ten-year follow-up of community death registers. The mortality risk of
      generalized anxiety, depression and mixed anxiety-depression was calculated after
      adjustment for demographic variables, physical illness, functional disabilities
      and social vulnerability. RESULTS: In generalized anxiety disorder and mixed
      anxiety-depression no significant excess mortality was found. In depression a
      significant excess mortality was found in men [HR 1.44 (1.09-1.89)] but not in
      women [HR 1.04 (0.87-1.24)] after adjustment for the different variables.
      CONCLUSIONS: In elderly persons depression increases the risk of death in men.
      Neither generalized anxiety nor mixed anxiety-depression are associated with
      excess mortality. Generalized anxiety disorder may even predict less mortality in
      depressive elderly people. The relation between generalized anxiety disorder and
      its possibly protective effect on mortality has to be further explored.

PMID- 16998781
TI  - Screening for amnestic mild cognitive impairment and early Alzheimer's disease
      with M@T (Memory Alteration Test) in the primary care population.
AB  - OBJECTIVES: To design and validate a new screening test for amnestic Mild
      Cognitive Impairment (A-MCI) and early stage Alzheimer's disease (AD). METHODS:
      We develop a verbal episodic and semantic memory test: the Memory Alteration Test
      (M@T). Discriminative validity was assessed in a population sample of 400 aged
      individuals from primary care population centres in Barcelona, Spain, 50 patients
      with A-MCI according to Petersen et al. criteria, and 66 with early AD (Global
      Deterioration Scale-4 stage) according to the NINCDS-ADRDA criteria. RESULTS: The
      M@T is quick, 5-min, and easy to administer and to score. M@T mean scores were
      significantly different between all groups: 41.4 (SD = 4.9) in the primary care
      population, 31.5 (SD = 3.9) in the A-MCI group and 21.8 (SD = 4.9) in early AD. A
      cut-off score of 37 points had a sensitivity of 96% and a specificity of 79% for
      A-MCI diagnosis (AUC = 0.932). A cut-off score of 28 points had a sensitivity of
      92% and a specificity of 98% for early AD diagnosis (AUC = 0.99) and a
      sensitivity of 87 % and specificity of 82% to differentiate between A-MCI and AD
      patients. CONCLUSION: The M@T provides efficient and valid screening for A-MCI
      and early stage AD, and discriminates between A-MCI and early AD patients.

PMID- 16998782
TI  - Prevalence and risk factors for depressive symptoms among veterans home elders in
      Eastern Taiwan.
AB  - BACKGROUND: Depression in the elderly has become a serious health care issue
      worldwide. However, no studies have determined the prevalence and risk factors
      for depressive symptoms among a representative sample of veterans home elders in
      Taiwan. OBJECTIVES: To determine the prevalence and risk factors for depressive
      symptoms among veterans home elders in eastern Taiwan. METHOD: Elderly veterans
      (n = 947) were recruited from four veterans homes in eastern Taiwan. RESULTS: The
      prevalence of depressive tendency was 35.5%. Logistic regression analysis
      demonstrated that depressive status in this sample was significantly predicted by
      poorer functional status, dissatisfaction with living situation, poorer perceived
      health status, and lower education level. CONCLUSIONS: The risk factors for
      depressive symptoms identified in this study need to be considered when assessing
      the health of elderly veterans. In addition, strategies to improve elderly
      veterans' perception of health status, physical function and living situation
      should be considered in interventions to reduce their depressive symptoms.

PMID- 16998783
TI  - Factors related to potentially harmful behaviors towards disabled older people by
      family caregivers in Japan.
AB  - OBJECTIVE: The purpose of the present study was to examine factors related to
      potentially harmful behaviors (PHB) by family caregivers towards their older
      family members. METHODS: Four hundred and twelve pairs of disabled older adults
      and their family caregivers participated in the study. All of these disabled
      older adults were users of visiting nursing services under the public Long-Term
      Care insurance system, who resided in one of the eight catchment areas of
      visiting nursing services in Kyoto Prefecture, Japan. The caregivers were asked
      to complete questionnaires in relation to their PHB towards their older family
      members, caregiver burden, patient-caregiver kinship, behavioral disturbances of
      their older adult, age and sex. Visiting nurses obtained the following
      information regarding the older adults: the severity of dementia; the severity of
      physical impairment; age and sex. RESULTS: More than 30% of the caregivers
      admitted PHB towards their older family members. The most frequently reported PHB
      included verbal aggression (16.8%) and ignoring (13.6%). A logistic regression
      analysis revealed that adult children (OR = 2.69, 95%CI = 1.23-5.89, p = 0.013)
      and caregivers of disabled older people with behavioral disturbances (OR = 3.61,
      95%CI = 1.65-7.90, p < 0.01) were more likely to show PHB. CONCLUSIONS: In the
      present study, PHB towards the older people by family caregivers was associated
      with patients' behavioral disturbances and patient-caregiver kinship, i.e. an
      adult child as a caregiver. These findings should be taken into account when
      planning strategies to prevent PHB by family members.

PMID- 16998784
TI  - Health care funding levels and patient outcomes: a national study.
AB  - BACKGROUND: Health care funding levels differ significantly across geographic
      regions, but there is little correlation between regional funding levels and
      outcomes of elderly Medicare beneficiaries. Our goal was to determine whether
      this relationship holds true in a non-Medicare population cared for in a large
      integrated health care system with a capitated budget allocation system. METHODS:
      We explored the association between health care funding and risk-adjusted
      mortality in the 22 Veterans Affairs (VA) geographic Networks over a six-year
      time period. Allocations to Networks were adjusted for illness burden using
      Diagnostic Cost Groups. To test the association between funding and risk-adjusted
      three-year mortality, we ran logistic regressions with single-year patient
      cohorts, as well as hierarchical regressions on a six year longitudinal data set,
      clustering on VA Network. RESULTS: A 1000 dollar increase in funding per unit of
      patient illness burden was associated with a 2-8% reduction in three-year
      mortality in cross sectional regressions. However, in longitudinal hierarchical
      regressions clustering on Network, the significant effect of funding level was
      eliminated. CONCLUSIONS: When longitudinal data are used, the significant cross
      sectional effect of funding levels on mortality disappear. Thus, the factors
      driving differences in mortality are Network effects, although part of the
      Network effect may be due to past levels of funding. Our results provide a
      caution for cross sectional examinations of the association between regional
      health care funding levels and health outcomes.

PMID- 16998785
TI  - Atmospheric pressure ion/molecule reactions for the selective detection of
      nitroaromatic explosives using acetonitrile and air as reagents.
AB  - Acetonitrile vapor and air are useful reagents for the selective detection of
      nitroaromatic compounds using atmospheric pressure ion/molecule reactions.
      Reagent ions CH2CN- and CN- generated from acetonitrile, and O-*, OH- and OOH-
      produced from the oxygen in air, react with vapor-phase and condensed-phase
      nitroaromatics in the course of atmospheric pressure chemical ionization (APCI)
      and desorption atmospheric pressure chemical ionization (DAPCI), respectively.
      The homogeneous and the heterogeneous phase reactions both lead to the formation
      of the same anionic adducts. These adducts have characteristic fragmentation
      patterns upon collisional activation, which makes these two reagents valuable for
      the selective detection of particular nitroaromatics, including explosives
      present as components of complex mixtures. Complementary information is available
      from the two reagents because their different chemistry facilitates analyte
      identification. DAPCI is demonstrated to be a useful ambient detection method for
      nitroaromatic explosives absorbed on surfaces.

PMID- 16998786
TI  - Characterization of typical chemical background interferences in atmospheric
      pressure ionization liquid chromatography-mass spectrometry.
AB  - The structures and origins of typical chemical background noise ions in positive
      atmospheric pressure ionization liquid chromatography/mass spectrometry (API
      LC/MS) are investigated and summarized in this study. This was done by
      classifying chemical background ions using precursor and product ion scans on
      most abundant background ions to draw a family tree of the commonly occurring
      chemical background ions. The possible structures and the origins of the major
      chemical background noise are clearly revealed in the family trees. In agreement
      with some suggestions in the literature, the chemical background ions studied so
      far can be classified mainly as either ions of contaminants (or their degradation
      fragments) or cluster-related ones. A significant contribution from the
      contaminants (airborne, from tubing and/or solvents) from plasticizer additives
      (phthalates, phenyl phosphates, sebacates and adipates, etc.) and silicones is
      concluded. These ions of contaminants can also serve as nuclei for the clustering
      of HPLC solvent or additives, such as water and acetic acid, thereby leading to a
      second family of background ions. This study explains the persistence of some
      chemical background noise even under fairly strong declustering conditions in API
      LC/MS. One of the other interesting conclusions is that there is a clear
      difference in structures between the chemical background ions and the protonated
      analytes generated under atmospheric pressure ionization. This conclusion will
      contribute to the on-going research efforts to exclusively remove or reduce the
      interference of chemical background noise in API LC/MS.

PMID- 16998787
TI  - Impact of antinucleants on transdermal delivery of testosterone from a spray.
AB  - The goal was to explore whether the incorporation of antinucleant polymers into a
      testosterone spray formulation could stabilize a putative supersaturated state
      and improve the delivery of the drug across the skin. Several antinucleants were
      screened using differential scanning calorimetry (DSC) and two candidates showed
      particular promise: a cyclodextrin derivative (RAMEB) and a
      vinylpyrrolidone/vinyl acetate copolymer (Kollidon VA64). These agents also
      improved significantly the long-term stability of saturated solutions of the
      drug. Further, using the method of mixed cosolvents, it was possible to create,
      in the presence of 5% w/v antinucleant polymer, supersaturated ethanol/propylene
      glycol/water (4:1:1 v/v) solutions of the drug with degrees of saturation between
      1.4 and 2.6; however, these metastable systems existed only transiently under
      carefully controlled conditions and had reverted back to equilibrium solubilities
      of the drug within 6 h. When the same solutions were administered to hairless rat
      skin in vitro from mechanical sprays, no improvement in testosterone delivery,
      relative to a nonstabilized control, was observed. It appears, therefore, that
      the in situ crystallization process of the drug is more complex and incompletely
      understood (and cannot be predicted from DSC experiments). The complicated
      evaporation/volatilization process, which takes place when a spray is pulverized,
      requires better characterization before the use of supersaturation for
      testosterone delivery can be optimized.

PMID- 16998789
TI  - Increased risk of gastrointestinal lymphoma in carriers of the 657del5 NBS1 gene
      mutation.
AB  - The NBS1 gene mutation, 657del5, frequent in the Slavic populations of Central
      Europe, is found in most patients with Nijmegen breakage syndrome (NBS), a
      recessive autosomal disorder with a very high incidence of non-Hodgkin lymphoma
      (NHL). We have previously described 2 heterozygous 657del5 mutation carriers
      among 42 adult NHL probands from Central Poland. Here we report 6 additional
      carriers of the 657del5 mutation and 2 carriers of the pathogenic NBS1 R215W
      mutation, among 186 other NHL patients also from Central Poland. The 657del5
      carrier frequency in the pooled group of these 228 patients was significantly
      higher than in population controls (OR 5.85, 95% CI: 2.29-15.00, p = 0.0001).
      Interestingly, 4 of these carriers were found among 37 patients with
      gastrointestinal lymphoma (OR 19.52, 95% CI: 5.82-65.42, p = 0.0002). These
      findings imply that heterozygous NBS1 germline mutations may contribute
      significantly to the overall incidence of NHL, especially of the gastrointestinal
      tract, in Central Europe.

PMID- 16998790
TI  - Melanoma cells interfere with the interaction of dendritic cells with NK/LAK
      cells.
AB  - Dendritic cells (DCs) and natural killer (NK) cells are key players at the
      interface between innate resistance and acquired immunity. NK cells can induce DC
      maturation, a differentiation process whereby DCs respond to a environmental
      stimulus and acquire the ability of eliciting adaptive immunity. Conversely,
      maturing DCs promote NK functions in vivo and in vitro. This interplay has
      important consequences on the immune response to pathogens and possibly to
      neoplastic cells. Here, we show that B16 melanoma cells actively modulate the
      interaction between DCs derived from bone marrow precursors and NK/LAK cells
      propagated from the spleen of C57BL/6 mice. DCs increased in a dose-dependent
      manner the ability of NK/LAK cells to kill melanoma cells and to produce
      cytokines. This activatory cross-talk entailed the production of IL-18 by DCs and
      of IFN-gamma by NK/LAK cells. Melanoma cells were not a passive target of NK
      activity; they regulated the outcome of the interaction between DCs and NK/LAK
      cells, inhibiting the in vitro production of cytokines as effectively as the
      genetic deletion of IL-18 or IFN-gamma. Interference with the NK/DC interaction
      possibly represents a mechanism used by growing tumors to evade the immune
      response.

PMID- 16998791
TI  - Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer
      patients.
AB  - Among Asian countries, Pakistan has the highest rates of breast and ovarian
      cancer. To assess the contribution of the BRCA1 and BRCA2 germ line mutations to
      these high rates, we conducted the first study of 176 Pakistani breast and
      ovarian cancer patients, selected on family history and on age of diagnosis.
      Comprehensive BRCA mutation screening was performed using a range of techniques,
      including denaturing high-pressure liquid chromatography, single strand
      conformational polymorphism analysis and protein truncation test, followed by DNA
      sequencing. Thirty deleterious germ-line mutations were identified in the 176
      families (17.0%), including 23 in BRCA1 and 7 in BRCA2. Four mutations, 185delAG,
      185insA, S1503X and R1835X, were recurrent; these accounted for 52% of all
      identified BRCA1 mutations. Haplotype analyses suggested founder effects for 3 of
      these. The prevalence of BRCA1 or BRCA2 mutations was 42.8% for families with
      multiple cases of breast cancer, and was 50.0% for the breast/ovarian cancer
      families. The prevalence of mutations was 11.9% for single cases of early-onset
      breast cancer (< or =30 years) and was 9.0% for single cases of early-onset
      ovarian cancer (< or =45 years). Our findings show that BRCA mutations account
      for a substantial proportion of hereditary breast/ovarian cancer and early-onset
      breast and ovarian cancer cases in Pakistan.

PMID- 16998792
TI  - Food groups and risk of hepatocellular carcinoma: A multicenter case-control
      study in Italy.
AB  - The role of diet, except for alcohol drinking and aflatoxin contamination, in the
      etiology of hepatocellular carcinoma (HCC) is unclear. A hospital-based case
      control study was conducted in Italy in 1999-2002, including 185 incident,
      histologically-confirmed cases of HCC. Controls were 412 subjects admitted to
      hospitals for acute, nonneoplastic diseases unrelated to diet. Dietary habits
      were assessed using a validated food-frequency questionnaire. Odds ratios (ORs)
      and the corresponding 95% confidence intervals (CI) were computed using
      unconditional multiple logistic regression, adjusting for hepatitis B (HBV) and
      hepatitis C (HCV) virus infection and alcohol drinking. Energy adjustment was
      carried out by means of the residual model. A significant inverse relation was
      found between intakes of milk and yoghurt (OR = 0.28; 95% CI: 0.13-0.61), white
      meats (OR = 0.44; 95% CI: 0.20-0.95), eggs (OR = 0.31; 95% CI: 0.14-0.69), and
      fruits (OR = 0.48; 95% CI: 0.22-1.05) and HCC risk. The favourable effect of high
      intakes of milk and yoghurt, white meats, eggs and fruits was consistent across
      strata of HBV and HCV infections. The present study supports the hypothesis of a
      role of diet in HCC aetiology. Dietary modifications may be indicated in subjects
      at high-risk for HCC.

PMID- 16998793
TI  - Differential expression and activation of NF-kappaB family proteins during oral
      carcinogenesis: Role of high risk human papillomavirus infection.
AB  - Oral cancer is one of the most common cancers in India and south-east Asian
      region consisting of more than 50% of all malignant tumors. Along with many known
      risk factors, infection of Human Papillomavirus (HPV) has been associated with
      the development of oral cancer and is suggested to modulate host cell
      transcription. Reciprocally, cellular transcription factors, such as NF-kappaB
      and AP-1 are known to modulate the expression of viral and other genes involved
      in the development of cancer. In the absence of data on NF-kappaB in relation to
      HPV in oral cancer, we studied the DNA binding activity and expression pattern of
      NF-kappaB family of proteins in different stages of oral cancer and correlated
      with HPV infection that has been associated with better prognosis of the disease.
      A total of 110 fresh oral tissue biopsies were collected comprising 10 normal
      controls, 34 precancer and 66 oral cancer lesions prior to
      chemotherapy/radiotherapy. Diagnosis of HPV was done by both consensus and type
      specific PCR. Electrophoretic mobility shift assays, western blots and
      immunohistochemical analysis were performed to assess the binding activity and
      expression pattern of NF-kappaB family of proteins (p50, p65, p52, c-Rel, RelB
      and Bcl-3) in oral tissue biopsies. Twenty seven percent (18/66) of the oral
      cancer biopsies showed the presence of HPV infection exclusively of high risk HPV
      type 16, which was primarily associated with the well differentiated squamous
      cell carcinomas (WDSCC). We observed a high constitutive activation of NF-kappaB
      with concomitant upregulated expression of all the NF-kappaB members in oral
      cancer tissues. Expression of NF-kappaB components gradually increased as the
      severity of lesion increased from precancer to invasive cancer. NF-kappaB p50 was
      found to be the major DNA binding component, which is indicative of
      homodimerization of p50 subunits. Interestingly, in HPV16 infected oral cancers
      although p50 showed high binding activity, p65 also showed a partial involvement
      as evidenced in supershift assay. Both by western blotting and
      immunohistochemistry, a differential overexpression and nuclear localization of
      p50, p65 and partially of Bcl-3 were observed in HPV16 positive oral cancer
      patients that also showed an over-expression of p21. We therefore, demonstrate a
      constitutive activation and differential expression of NF-kappaB proteins, which
      change as a function of severity of oral lesions during development of oral
      cancer. The NF-kappaB DNA binding is primarily due to homodimerization of p50 but
      infection of high risk HPV promotes participation of p65 in NF-kappaB complex
      formation, leading to heterodimerization of p50/p65. We propose that the
      involvement of p65 in HPV infected oral cancer may be linked to improved
      differentiation and better prognosis of the disease when treated.

PMID- 16998794
TI  - ERBB3 kinase domain mutations are rare in lung, breast and colon carcinomas.

PMID- 16998795
TI  - Severe pulmonary metastasis in obese and diabetic mice.
AB  - Although obesity is known as a risk factor for several human cancers, the
      association of obesity with cancer recurrence and metastasis remains to be
      characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were
      intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number
      of experimental lung colonies was markedly promoted in these mice when compared
      with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable
      when cells were inoculated orthotopically. The use of B16-BL6 cells stably
      transfected with the luciferase gene revealed that the increased metastasis
      reflected a difference mainly within 6 hr after the intravenous inoculation of
      tumor cells. Administration of recombinant leptin in ob/ob mice abolished the
      increase in metastasis early on as well as the decrease in the splenic NK cell
      number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody
      abrogated the enhanced metastasis in db/db mice. These results demonstrate that
      metastasis is markedly promoted in diabetic and obese mice mainly because of
      decreased NK cell function during the early phase of metastasis.

PMID- 16998796
TI  - Targeting the exogenous htPAm gene on goat somatic cell beta-casein locus for
      transgenic goat production.
AB  - Combining gene targeting of animal somatic cells with nuclear transfer technique
      has provided a powerful method to produce transgenic animal mammary gland
      bioreactor. The objective of this study is to make an efficient and reproducible
      gene targeting in goat fetal fibroblasts by inserting the exogenous htPAm cDNA
      into the beta-casein locus with liposomes or electroporation so that htPAm
      protein might be produced in gene-targeted goat mammary gland. By gene-targeting
      technique, the exogenous htPAm gene was inserted to milk goat beta-casein gene
      sequences. Fetal fibroblasts were isolated from Day 35 fetuses of Guanzhong milk
      goats, and transfected with linear gene-targeting vector pGBC4htPAm using
      Lipefectamin-2000 and electoporation, respectively. Forty-eight gene-targeted
      cell colonies with homologous recombination were obtained, and three cell
      colonies were verified by DNA sequence analysis within the homologous
      recombination region. Using gene-targeted cell lines as donor cells for nuclear
      transfer, a total of 600 reconstructed embryos had been obtained, and 146
      developed cloned embryos were transferred to 16 recipient goats, and finally
      three goats showed pregnancy at Day 90.

PMID- 16998797
TI  - Effects of delayed excision of oviducts/ovaries on mouse oocytes and embryos.
AB  - To achieve the best and reproducible results of experiments, effects of delayed
      excision of oviducts/ovaries on mouse ovarian/ovulated oocytes and embryos have
      been studied. Oviducts/ovaries were excised at different times after death of
      mice and effects of the postmortem interval on ovarian/ovulated oocytes and
      embryos were analyzed. When oviduct excision was delayed 10 min, many ovulated
      oocytes lysed or underwent in vitro spontaneous activation, and this postmortem
      effect aggravated with the extension of postmortem interval and oocyte aging.
      Oocytes from different mouse strains responded differently to delayed oviduct
      removal. Delayed oviduct excision did not cause lysis of zygotes or embryos but
      compromised their developmental potential. When ovaries were excised at 30 min
      after death, percentages of atretic follicles increased while blastocyst cell
      number declined significantly after oocyte maturation in vitro. Preservation of
      oviducts in vitro, in intact or opened abdomen at different temperatures and
      histological analysis of oviducts from different treatments suggested that toxic
      substance(s) were secreted from the dying oviducts which induced oocyte lysis and
      spontaneous activation and both this effect itself and the sensitivity of oocytes
      to this effect was temperature dependent. It is concluded that a short delay of
      oviduct/ovary removal had marked detrimental effects on oocytes and embryos. This
      must be taken into account in experiments using oocytes or embryos from
      slaughtered animals. The data may also be important for estimation of the time of
      death in forensic medicine and for rescue of oocytes from deceased valuable or
      endangered mammals.

PMID- 16998798
TI  - Exogenous expression of claudin-5 induces barrier properties in cultured rat
      brain capillary endothelial cells.
AB  - Claudins are thought to be major components of tight junctions (TJs), and claudin
      5 and -12 are localized at TJs of the blood-brain barrier (BBB). Claudin-5
      deficient mice exhibit size-selective (<800 Da) opening of the BBB. The purpose
      of this study was to clarify the expression levels of claudin-5 and -12 in rat
      brain capillary endothelial cells, and to examine the ability of claudin-5 to
      form TJs in cultured rat brain capillary endothelial cells (TR-BBB). Expression
      of claudin-5 mRNA in rat brain capillary fraction was 751-fold greater than that
      of claudin-12. The level of claudin-5 mRNA in the rat brain capillary fraction
      (per total mRNA) was 35.6-fold greater than that in whole brain, while the level
      of claudin-12 mRNA was only 13.9% of that in whole brain, suggesting that
      expression of claudin-12 mRNA is not restricted to brain capillaries.
      Transfection of TR-BBB cells with the claudin-5 gene afforded TR-BBB/CLD5 cells,
      which showed no change in expression of claudin-12 or ZO-1, while the expressed
      claudin-5 was detected at the cell-cell boundaries. The permeability surface
      product of [(14)C]inulin at a TR-BBB/CLD5 cell monolayer was significantly
      smaller (P < 0.01) than that for the parental TR-BBB cells, and the values of the
      permeability coefficient (Pe) were 1.14 x 10(-3) and 11.6 x 10(-3) cm/min,
      respectively. These results indicate that claudin-5, but not claudin-12, is
      predominantly expressed in brain capillaries, and plays a key role in the
      appearance of barrier properties of brain capillary endothelial cells.

PMID- 16998799
TI  - Oligopeptides impairing the Myc-Max heterodimerization inhibit lung cancer cell
      proliferation by reducing Myc transcriptional activity.
AB  - Deregulated CMYC gene causes cell transformation and is often correlated with
      tumor progression and a worse clinical outcome of cancer patients. The
      transcription factor Myc functions by heterodimerizing with its partner, Max. As
      a strategy to inhibit Myc activity, we have synthesized three small peptides
      corresponding to segments of the leucine zipper (LZ) region of Max. The purpose
      of these peptides is to occupy the site of recognition between Myc and Max
      located in the LZ and inhibit-specific heterodimerization between these proteins.
      We have used the synthesized oligopeptides in two lung cancer cell lines with
      different levels of Myc expression. Results demonstrate that: (i) the three
      peptides resulted equally effective in competing the interaction between Myc and
      Max in vitro; (ii) they were efficiently internalized into the cells and
      significantly inhibited cell growth in the cells showing the highest Myc
      expression; (iii) one specific peptide, only nine aminoacids long, efficiently
      impaired the transcriptional activity of Myc in vivo, showing a more stable
      interaction with this protein. Our results are relevant to the development of
      novel anti-tumoral therapeutic strategies, directed to Myc-overexpressing tumors.

PMID- 16998800
TI  - The role of p63 in germ cell apoptosis in the developing testis.
AB  - The fetal and neonatal development of male germ cells (gonocytes) is a poorly
      understood but crucial process for establishing fertility. In rodents, gonocytes
      go through two phases of proliferation accompanied by apoptosis and separated by
      a quiescent period during the end of fetal development. P63 is a member of the
      P53 gene family that yields six isoforms. We detected only the p63 protein and no
      p53 and p73 in the nucleus of the gonocytes of mouse testes. We report for the
      first time the ontogeny of each p63 mRNA isoform during testis development. We
      observed a strong expression of p63gamma mRNA and protein when gonocytes are in
      the quiescent period. In vitro treatment with retinoic acid prevented gonocytes
      from entering the quiescent period and was correlated with a reduced production
      of p63gamma isoform mRNA. We investigated the function of p63 by studying the
      testicular phenotype of P63-null mice. P63 invalidation slightly, but
      significantly increased the number of gonocytes counted during the quiescent
      period. As P63-null animals die at birth we used an original organ culture that
      mimicked neonatal in vivo development to study further the testicular
      development. P63 invalidation resulted in a sharply increased number of gonocytes
      during the culture period due to a decrease in spontaneous apoptosis with no
      change in proliferation. P63 invalidation also caused abnormal morphologies in
      the germ cells that were also found in P63(+/-) adult male mice. Thus, p63
      appears as an important regulator of germ cell development.

PMID- 16998801
TI  - Prostaglandin E(2) protects human lung fibroblasts from cigarette smoke extract
      induced apoptosis via EP(2) receptor activation.
AB  - Prostaglandin E(2) (PGE(2)) has been shown to have a strong cytoprotective
      effect, inhibiting apoptosis. In the present study, we evaluated whether PGE(2)
      has a protective effect on cigarette smoke extract (CSE)-induced apoptosis in
      human lung fibroblasts. Apoptosis was assessed by various methods, including DNA
      content analysis. CSE (15%-20%) led to apoptosis and induced imbalance in favor
      of pro- over anti-apoptotic protein expression and activated caspases. PGE(2)
      blocked CSE-induced apoptosis and modulated the balance of pro- and anti
      apoptotic proteins and decreased the activation of caspases. This anti-apoptotic
      effect was mediated via EP(2) receptor activation as the EP(2) agonist butaprost
      mimicked PGE(2) activity and siRNA for the EP(2) receptor blocked it. An adenylyl
      cyclase inhibitor was found to abolish the PGE(2)-mediated cytoprotective effect.
      Correspondingly, c-AMP analogs blocked CSE-induced apoptosis. Consistently, the
      protein kinase A (PKA) inhibitor KT-5720 abolished PGE(2)-mediated protection.
      PGE(2) and butaprost phosphorylated Bad and KT-5720 blocked phosphorylation.
      These results suggest that PGE(2) inhibits CSE-induced apoptosis via EP(2)
      receptor activation and activation of PKA, which leads to an alteration in the
      balance between pro- and anti-apoptotic factors. Through such a mechanism, PGE(2)
      may alter survival of cells in the smoke-exposed lungs, thus affecting the
      pathogenesis of cigarette smoke-induced disease.

PMID- 16998802
TI  - Methotrexate-induced mucositis in mucin 2-deficient mice.
AB  - The mucin Muc2 or Mycin2 (Muc2), which is the main structural component of the
      protective mucus layer, has shown to be upregulated during chemotherapy-induced
      mucositis. As Muc2 has shown to have protective capacities, upregulation of Muc2
      may be a counter reaction of the intestine protecting against mucositis.
      Therefore, increasing Muc2 protein levels could be a therapeutic target in
      mucositis prevention or reduction. Our aim was to determine the role of Muc2 in
      chemotherapy-induced mucositis. Mucositis was induced in Muc2 knockout (Muc2(-/
      )) and wild type (Muc2(+/+)) mice by injecting methotrexate (MTX). Animals were
      weighed and sacrificed on Days 2-6 after MTX treatment and jejunal segments were
      analyzed. Before MTX treatment, the small intestine of Muc2(+/+) and Muc2(-/-)
      mice were similar with respect to epithelial morphology and proliferation.
      Moreover, sucrase-isomaltase and trefoil factor-3 protein expression levels were
      comparable between Muc2(+/+) and Muc2(-/-) mice. Up to Day 3 after MTX treatment,
      percentages of weight-loss did not differ. Thereafter, Muc2(+/+) mice showed a
      trend towards regaining weight, whereas Muc2(-/-) mice continued to lose weight.
      Surprisingly, MTX-induced intestinal damage of Muc2(-/-) and Muc2(+/+) mice was
      comparable. Prior to MTX-injection, tumor necrosis factor-alpha and interleukin
      10 mRNAs were upregulated in Muc2(-/-) mice, probably due to continuous exposure
      of the intestine to luminal antigens. Muc2 deficiency does not lead to an
      increase in chemotherapy-induced mucositis. A possible explanation is the
      mechanism by which Muc2 deficiency may trigger the immune system to release
      interleukin-10, an anti-inflammatory cytokine before MTX-treatment.

PMID- 16998803
TI  - Cyclophilin C-associated protein is up-regulated during wound healing.
AB  - Cyclophilin C-associated protein (CyCAP) is identified from macrophages. It
      locates in intracellular, membrane bound and extracellular, suggesting it has an
      important role, however both of its regulation and function have not been
      elucidated. The expression of CyCAP in skin and during wound healing is also
      unknown. We demonstrate that CyCAP is expressed in both dermal fibroblasts and
      keratinocytes. In the dermis, the majority of CyCAP protein is located
      intracellular in a filamentous protein form while a lesser amount is in the
      extracellular matrix (ECM). CyCAP gene and protein expression is increased 1 day
      after skin wound healing in both fetal and adult rats and remains elevated level
      up to 1 week in adult rats. Immunohistochemistry studies demonstrate that the
      increased CyCAP expression locates mainly to inflammatory cells, including
      macrophages, monocytes and lymphocytes during wound healing. Interferon-gamma
      increases CyCAP gene and protein expression in cultured rat fibroblasts. We also
      found that wound healing is slower and less collagen is expressed in skin of
      CyCAP null mice. These data are the first observations of CyCAP expression in
      skin and during wound repair. Our data indicates that CyCAP is regulated by
      IFNgamma and may function on immune defense in macrophages, lymphocytes, dermal
      fibroblasts and keratinocytes during wound healing.

PMID- 16998804
TI  - ERK1/2 regulates two sequential steps promoting monocyte survival to
      peroxynitrite.
AB  - Previous studies from our laboratory indicate that cytosolic phospholipase A(2)
      (cPLA(2))-released arachidonic acid promotes monocyte/macrophage survival in the
      presence of peroxynitrite. In particular, the lipid messenger is metabolised by 5
      lipoxygenase (5-LO) to 5-hydroxyeicosatetraenoic acid and causes the
      mitochondrial translocation of protein kinase Calpha (PKCalpha), an event
      associated with the cytosolic accumulation of Bad and Bax. Here we show that
      phosphorylation reactions driven by extracellular regulated kinase 1/2 (ERK1/2)
      critically regulate the activation/nuclear translocation of 5-LO. Inhibition of
      ERK1/2 was invariably associated with the cytosolic localisation of PKCalpha, the
      mitochondrial accumulation of Bad and Bax and with a rapid mitochondrial
      permeability transition-dependent necrosis. All these events were prevented by
      nanomolar concentrations of 5-hydroxyeicosatetraenoic acid. Hence, in addition to
      the previously characterised effects on cPLA(2), ERK1/2 critically regulates 5-LO
      activity in the absence of additional downstream targets in the survival
      signalling preventing peroxynitrite toxicity.

PMID- 16998805
TI  - Comparison of mice born after intracytoplasmic sperm injection with in vitro
      fertilization and natural mating.
AB  - The procedures of in vitro fertilization (IVF) and intracytoplasmic sperm
      injection (ICSI) are routinely used in modern medicine to overcome infertility
      and, in animal husbandry, to propagate lines with compromised fertility. However,
      there remains concern that manual selection and injection of whole sperm into
      oocytes could contribute to pre- and postnatal developmental defects. To address
      this, we have used gene expression profiling and immunophenotyping to
      characterize offspring generated by these procedures. We used gametes from
      glutathione peroxidase 1 knockout (Gpx1-/-) mice as a sensitized screen
      responsive to oxidative stress from artificial reproduction technologies (ART).
      There were no differences between IVF and ICSI derived offspring in gene
      expression patterns, and minor differences in hematopoietic parameters.
      Furthermore there were only minor differences between these IVF and ICSI pups and
      those derived from natural mating. These data demonstrate for the first time in
      that there is no significant phenotypic affects of ICSI when compared to IVF and
      we identified a relatively minor influence of the artificial fertilization
      methods on phenotype of offspring compared with natural mating. These
      observations would support the use of ICSI for derivation of mutant mouse lines
      and may be of some importance for the use of this technique in human ART.

PMID- 16998806
TI  - Absence of Bcl-2 expression favors response to the short-term administration of
      diethylstilbestrol diphosphate in prostate Cancer.
AB  - BACKGROUND: Neoadjuvant hormone therapy remains a controversial issue in spite of
      multiple studies having been performed. METHODS: We performed short-term (10
      days) treatment with diethylstilbestrol (DES) in 30 patients with stages T2 or T3
      prostate cancer (PCa). All the patients underwent needle core prostate biopsy
      before and radical prostatectomy within a month after the start of the endocrine
      therapy. The histological effects in PCa and the changes in morphological and
      clinical parameters and their association were elucidated. RESULTS: Serum PSA (P
      < 0.001), Ki-67 PI (P = 0.022), and AR (P = 0.002) expression decreased after the
      treatment. An obvious effect (Grade 1-3) of endocrine treatment was seen in 11 of
      30 patients and was associated with a prominent PSA decrease (P = 0.0274) and
      with older age (P = 0.0026). Pre-treatment specimens from a group without any
      effects of endocrine therapy had a higher frequency of Bcl-2 positivity (57.9%)
      compared to the group of Grade 1-3 effects (27.3%). Prostatectomy specimens
      presented with significantly higher AI in Bcl-2 negative cases (P = 0.0029) and
      pre treatment Bcl-2 was associated with a higher AI in Grade 1-3 patients (P =
      0.0393). CONCLUSIONS: Older age is a predictor of histological effects in short
      term hormone treatment of PCa. A lower Bcl-2 in biopsy specimens presented more
      frequently in the patients who experienced a prominent effect of endocrine
      therapy, and it was also useful to predict a significantly higher AI in Grade 1-3
      patients. Histological effects are also associated with the PSA decrease,
      reflecting the clinically meaningful shrinkage of tumors and a decrease of tumor
      burden.

PMID- 16998807
TI  - Modelling smoking history using a comprehensive smoking index: application to
      lung cancer.
AB  - The mathematical representation of smoking history is an important tool in
      analysis of epidemiological and clinical data. Hoffmann and colleagues recently
      proposed a single aggregate measure of smoking exposure that incorporates
      intensity, duration, and time since cessation. This comprehensive smoking index
      (CSI), which may be incorporated in any regression model, depends on a half-life
      (tau) and a lag (delta) parameters that have to be fixed a priori, or estimated
      by maximizing the fit. The CSI has not previously been used for analysis of
      cancer data. Following some preliminary results on smoking and lung cancer, the
      authors proposed a new version of the CSI for lung cancer. The aim of this study
      was to investigate the performance of the original and the new versions of the
      CSI in the analysis of three data sets from two case-control studies of lung
      cancer undertaken in Montreal, in 1979-1985 in males, and in 1996-2000 in both
      males and females. The estimates of tau and delta for both versions of the CSI
      were similar across data sets. The new version of the CSI fitted the three data
      sets systematically although moderately better than the original version, and at
      least as well as other representations of lifetime smoking history that used
      separate variables for time since cessation and cumulative amount of cigarettes
      smoked. The results suggest that the CSI may be an attractive and parsimonious
      alternative to conventional modelling of different aspects of smoking history for
      lung cancer.

PMID- 16998808
TI  - The homozygous P582S mutation in the oxygen-dependent degradation domain of HIF-1
      alpha is associated with increased risk for prostate cancer.
AB  - BACKGROUND: The heterodimeric transcription factor HIF-1 (hypoxia-inducible
      factor 1), consisting of a critically regulated HIF-1 alpha subunit and a
      constitutively expressed HIF-1 beta subunit, is a master regulator of genes
      involved in adaptation and survival under low-oxygen conditions. Increased levels
      of HIF-1 activity are associated with increased tumor aggressiveness, therapeutic
      resistance, and mortality. METHODS: We studied 402 prostate cancer patients for
      the presence of the 1772C > T (P582S) and 1790G > A (A588T) mutations within the
      oxygen-dependent domain of HIF-1 alpha. RESULTS: Homozygosity for the P582S
      mutation was fourfold greater among prostate cancer patients compared to controls
      (OR = 4.10 [C.I. 95% 1.11 < OR < 17.87], P = 0.018). The existence of this
      mutation in prostate cancer patients was not associated with any of the clinical
      or pathological characteristics of the disease. No significant differences were
      found between the frequencies of A588T mutation in prostate cancer patients and
      controls. CONCLUSIONS: Our data suggest that homozygous HIF1A P582S mutation
      confers significant susceptibility to prostate cancer.

PMID- 16998809
TI  - Stretch-activated signaling pathways responsible for early response gene
      expression in fetal lung epithelial cells.
AB  - High-tidal volume ventilation has been shown to increase the expression of
      several inflammation-associated genes prior to overt physiologic lung injury.
      Herein, using an in vitro stretch system, we investigated the mechanotransduction
      pathways involved in ventilation-induced expression of these early response genes
      (i.e., early growth response gene (Egr)1, heat-shock protein (HSP)70, and the pro
      inflammatory cytokines interleukin (IL)-1beta, IL-6, and MIP-2). Mechanical
      stretch of fetal lung epithelial cells activated various signaling pathways,
      resulting in transient or progressive increases in gene expression of the early
      response genes. The transient increase in Egr1 and IL-6 expression was mediated
      via p44/42 mitogen-activated protein kinase (p44/42 MAPK), while nuclear factor
      kappaB (NF-kappaB) was responsible for the sustained and progressive increase in
      expression of HSP70 and MIP-2. Blockage of Egr-1 expression did not affect the
      upregulation of IL-6, HSP70, MIP-2, and itself by stretch. Inhibition of calcium
      mobilization abolished stretch-induced p44/42 MAPK activation and NF-kappaB
      nuclear translocation as well as increased expression of all early response
      genes. Similar results were obtained with an inhibitor of Ras. These results
      suggest that mechanical stretch of fetal lung epithelial cells evokes a complex
      network of signaling molecules, which diverge downstream to regulate the temporal
      expression of a unique set of early response genes, but upstream converge at
      calcium. Thus, calcium mobilization may be a point of hierarchical integration of
      mechanotransduction in lung epithelial cells.

PMID- 16998810
TI  - SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity.
AB  - The tumor suppressor p53-related p73 shares significant amino-acid sequence
      identity with p53. Like p53, p73 recognizes canonical p53 DNA-binding sites and
      activates p53-responsive target genes and induces apoptosis. Moreover, SIRT1
      binds to p53 while repressing the expression of their target genes. Here, we
      report that SIRT1 also binds to p73 and suppresses p73-dependent transcriptional
      activity. SIRT1 in human cells reduces the transcriptional activity of p73, and
      partly inhibits apoptosis induced by p73. Furthermore, SIRT1 can deacetylate p73
      protein acetylation both in vivo and in vitro. Collectively, these data suggest
      that SIRT1 can modulate p73 activity via deacetylation.

PMID- 16998811
TI  - Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16(INK4A),
      p27(KIP1), p21(WAF1), Ki-67 expression patterns in gastric cancer.
AB  - Although the considerable progress against gastric cancer, it remains a complex
      lethal disease defined by peculiar histological and molecular features. The
      purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53,
      p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible
      correlations with clinicopathological factors. The expression patterns were
      examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type,
      and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in
      AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach
      cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic
      pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2
      was found in the intestinal-type and correlated with the risk of distant
      metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein
      may have a prognostic value in this type of cancer. Interestingly, a strong
      inverse correlation was observed between p27(KIP1) expression levels and the risk
      of advanced disease and metastasis (P < 0.05), and a positive correlation between
      the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05),
      confirming the traditionally accepted role for these tumor-suppressor genes in
      gastric cancer. Finally, a direct correlation was found between the expression
      levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was
      statistically significant (P < 0.05). Altogether, these data may help shed some
      additional light on the pathogenetic mechanisms related to the two main gastric
      cancer histotypes and their invasive potentials.

PMID- 16998812
TI  - Systematic replication study of reported genetic associations in prostate cancer:
      Strong support for genetic variation in the androgen pathway.
AB  - BACKGROUND: Association studies have become a common and popular method to
      identify genetic variants predisposing to complex diseases. Despite considerable
      efforts and initial promising findings, the field of prostate cancer genetics is
      characterized by inconclusive reports and no prostate cancer gene has yet been
      established. METHODS: We performed a literature review and identified 79
      different polymorphisms reported to influence prostate cancer risk. Of these, 46
      were selected and tested for association in a large Swedish population-based case
      control prostate cancer population. RESULTS: We observed significant (P < 0.05)
      confirmation for six polymorphisms located in five different genes. Three of them
      coded for key enzymes in the androgen biosynthesis and response pathway; the CAG
      repeat in the androgen receptor (AR) gene (P = 0.03), one SNP in the CYP17 gene
      (P = 0.04), two SNPs in the SRD5A2 gene (P = 0.02 and 0.02, respectively), a
      deletion of the GSTT1 gene (P = 0.006), and one SNP in the MSR1 gene, IVS5-59C >
      A, (P = 0.009). CONCLUSIONS: Notwithstanding the difficulties to replicate
      findings in genetic association studies, our results strongly support the
      importance of androgen pathway genes in prostate cancer etiology.

PMID- 16998813
TI  - Regulation of growth of prostate cancer cells selected in the presence of
      interleukin-6 by the anti-interleukin-6 antibody CNTO 328.
AB  - BACKGROUND: Interleukin-6 (IL-6) is a multifunctional regulator of cellular
      events in prostate cancer. LNCaP-IL-6+ cells selected in the presence of IL-6
      were taken for assessment of effects of the chimeric monoclonal anti-IL-6
      antibody CNTO 328. METHODS: Cell viability was assessed after treatment with CNTO
      328 by the ATP assay. Expression of Bcl-2 and Bax and activation of signaling
      pathways were evaluated by Western analysis. Nude mice were inoculated with LNCaP
      IL-6+ cells and treated with CNTO 328. The tumors were analyzed by
      immunohistochemistry for expression of Ki-67, tissue transglutaminase, and
      vascular endothelial growth factor. RESULTS: CNTO 328 caused a statistically
      significant inhibition of cell viability. The protein levels of Bcl-2 and the
      phosphorylation of ERK1/2 mitogen-activated protein kinases were decreased by the
      anti-IL-6 antibody. Treatment with CNTO 328 yielded an increase in the
      phosphorylation of signal transducers and activators of transcription factor 3.
      The mean tumor volume in animals inoculated with LNCaP-IL-6+ cells and treated
      with CNTO 328 was insignificantly lower than that in animals treated with the
      control antibody. There was a statistically significant decrease in the
      percentage of Ki-67-positive cells in CNTO 328-treated tumors. CONCLUSION: CNTO
      328 has a potential in prostate cancer therapy and could be further tested in
      various combination experimental treatments.

PMID- 16998814
TI  - Embryo quality and production efficiency of porcine parthenotes is improved by
      phytohemagglutinin.
AB  - In vitro production of porcine embryos has become routine in most laboratories
      but the yield and quality of the resultant blastocysts remain suboptimal.
      Phytohemagglutinin (PHA) is an N-acetylgalactosamine/galactose sugar-specific
      lectin with a wide variety of biological activities including mitogenesis,
      mediation of cell recognition, and agglutination of cells. This study was
      therefore, designed to investigate the effect of PHA on the preimplantation
      embryo development and quality of in vitro produced porcine parthenotes.
      Parthenogenetic presumptive diploid zygotes were produced in vitro by electrical
      activation and cultured in the absence or presence of PHA at different
      concentrations (0, 5, 10, 15, 20 microg/ml). There were no significant
      differences in the cleavage rate of porcine parthenotes in control and treatment
      groups at all tested concentrations of PHA (P < 0.05). However, supplementation
      of PHA at the concentration of 15 microg/ml significantly improved the blastocyst
      rate (68.9 +/- 1.5% vs. 43.1 +/- 4.1%), hatching rate (25.8 +/- 3.1% vs. 8.9 +/-
      2.0%), and total nuclei number (95.5 +/- 9.3 vs. 63.4 +/- 4.3) when compared to
      control group (P > 0.05). TUNEL labeling revealed that blastocysts in PHA group
      were less predisposed to biochemical apoptosis than in control group while total
      apoptosis and nuclear fragmentation remained unaltered. Real-time reverse
      transcription-polymerase chain reaction (RT-PCR) analysis further revealed that
      PHA decreased the expression ratio of BAX/BCL-XL and enhanced the relative
      abundance of IGF2 transcripts. Therefore, our study suggests that PHA improves
      the blastocyst yield and quality by enhancing blastocyst expansion, hatching, and
      total cell number and decreasing the apoptosis by positively modulating the
      expression of embryo survival related genes.

PMID- 16998815
TI  - Risks of hyperthermia associated with hot tub or spa use by pregnant women.
AB  - There are a limited number of human studies linking hot tub or spa use during
      early pregnancy to increased risks for neural tube defects (NTDs) or spontaneous
      abortion. However, these data can be considered in the context of human studies
      that have demonstrated an association between high maternal fever in early
      pregnancy and NTDs. In addition, there is a large volume of animal literature
      suggesting that, regardless of the heat source, an elevated core maternal
      temperature at or above the threshold of 2 degrees C over baseline, as well as
      timing and duration of exposure, are the critical factors in conferring risk.
      Therefore, the potential for hot tub or spa use to increase core maternal body
      temperature to risky levels and thus increase the risk for NTDs is likely. A
      woman who knows or who may not yet be aware that she is pregnant should be
      advised of the recommended limits of exposure. She should also be aware of the
      possible variability in hot tub or spa temperature readings and be able to
      accurately monitor maximum water temperature in the hot tub or spa so that her
      body temperature can be maintained below 38.9 degrees C.

PMID- 16998816
TI  - Wnt9b is the mutated gene involved in multifactorial nonsyndromic cleft lip with
      or without cleft palate in A/WySn mice, as confirmed by a genetic complementation
      test.
AB  - BACKGROUND: Nonsyndromic cleft lip (CL) with or without cleft palate (CLP) is a
      common human birth defect with complex genetic etiology. One of the unidentified
      genes maps to chromosome 17q21. A mouse strain, A/WySn, has CLP with complex
      genetic etiology that models the human defect, and 1 of its causative genes,
      clf1, maps to a region homologous to human 17q21. Extensive studies of the
      candidate region pointed to a novel insertion of an IAP transposon 3' from the
      gene Wnt9b as the clf1 mutation. Independently a recessive knockout mutation of
      Wnt9b (Wnt9b-) was reported to cause a lethal syndrome that includes some CLP.
      METHODS: A standard genetic test of allelism between clf1 and the Wnt9b- mutation
      was done. A total of 83 F1 embryos at gestation day 14 (GD 14) from Wnt9b-/+
      males crossed with A/WySn females, and 79 BC1 GD 14 embryos from F1 Wnt9b-/clf1
      males back-crossed to A/WySn females were observed for CL. Embryo genotypes at
      clf1 and Wnt9b were obtained from DNA markers. Genotypes for a second unlinked
      modifier locus from A/WySn, clf2, were similarly obtained. RESULTS: The compound
      mutant embryos (Wnt9b-/clf1) had high frequencies of CL: 27% in the F1 and 63% in
      the BC1. The clf2 modifier gene was found to have 3 alleles segregating in this
      study and to strongly influence the penetrance of CL in the compound mutant.
      CONCLUSIONS: The noncomplementation of clf1 and Wnt9b- confirms that clf1 is a
      mutation of the Wnt9b gene. The homologous human WNT9B gene and 3' conserved
      noncoding region should be examined for a role in human nonsyndromic CLP.

PMID- 16998817
TI  - Gestational stage sensitivity to ultrasound effect on postnatal growth and
      development of mice.
AB  - BACKGROUND: An experiment was conducted to find out whether ultrasound exposure
      leads to changes in postnatal growth and development in the mouse. METHODS: A
      total of 15 pregnant Swiss albino mice were exposed to diagnostic levels of
      ultrasound (3.5 MHz, 65 mW/cm2, I(SPTP) = 1 mW/cm2 Intensity(Spatial Peak
      Temporal Peak), I(SATA) = 240 mW/cm2 Intensity(Spatial Average-Temporal Average))
      for 30 min for a single day between days 10 and 18 of gestation (GD 10-18).
      Virgin female mice were placed with same age group males for mating in the ratio
      2 females : 1 male and examined the next morning for the presence of vaginal
      plug, a sign of successful copulation. The females with vaginal plugs were
      separated and labeled as 0-day pregnant. Maternal vaginal temperature was also
      measured. A sham exposed control group of 15 pregnant mice was maintained for
      comparison. All exposed as well as control animals were left to complete
      gestation and parturition. Their offspring were used in our further studies. They
      were monitored during early postnatal life for standard developmental markers,
      postnatal mortality, body weight, body length, head length, and head width, and
      growth restriction was recorded up to 6 weeks of age. RESULTS: An exposure to
      ultrasound induced nonsignificant deviations in the maternal vaginal temperature
      or developmental markers. Significant low birth weight was observed in the
      present study, after exposure at GD 11, 12, 14, and 16. However, 14 and 16 days
      postcoitus during the fetal period appears to be the most sensitive to the
      ultrasound effect, in view of the number of different effects as well as severity
      of most of the observed effects when exposed on these gestation days.
      CONCLUSIONS: The results indicate that diagnostic ultrasound can induce harmful
      effects on mouse growth and development when given at certain critical periods of
      gestation.

PMID- 16998818
TI  - Castration rapidly decreases local insulin-like growth factor-1 levels and
      inhibits its effects in the ventral prostate in mice.
AB  - BACKGROUND: The mechanisms by which castration induces prostate involution are
      largely unknown. METHODS: Early responses to castration in mouse ventral prostate
      (VP) were explored by quantitative microscopy, cDNA array expression,
      quantitative RT-PCR, and Western blot analysis. As several changes occurred in
      the insulin-like growth factor (IGF) system this was studied in more detail.
      Laser micro-dissection was used to localize sites of IGF-1 and IGF-1 receptor
      (IGF-R1) production. IGF-1 protein levels and IGF-R1 mediated signaling via
      insulin regulated substrate 1 and 2 (IRS-1 and 2) were examined. IGF-1 was
      injected into the VP in intact, and castrated mice and effects studied 1 day
      later. RESULTS: IGF-1 and IGF binding protein 2 (IGFBP-2) mRNA were rapidly
      reduced whereas IGFBP-3 and IGF-R1 mRNA were increased after castration. IGF-1
      was principally produced in the stromal compartment, while IGF-R1 was produced in
      both epithelial and stromal cells. IGF-1 and IRS-1 protein levels were decreased
      1 and 3 days after castration, respectively, while IRS-2 was unchanged.
      Inactivating phosphorylation of IRS-1 at serine 307 was increased 1 day after
      castration, and activating phosphorylation at tyrosine 612 was decreased 2 days
      later. These changes were accompanied by decreased cell proliferation and
      increased cell death in the glandular and vascular compartment. Local injection
      of IGF-1 increased vascular density and epithelial cell proliferation in intact
      mice, but had no effect in castrated animals. CONCLUSION: Decreased IGF-1 levels
      and action may mediate some of the key features of castration-induced prostate
      involution.

PMID- 16998819
TI  - Castration-induced epithelial cell death in human prostate tissue is related to
      locally reduced IGF-1 levels.
AB  - BACKGROUND: Castration rapidly reduces stroma insulin-like growth factor (IGF)-1
      synthesis and action in mouse prostate epithelium. We explore if similar changes
      are of importance for castration-induced prostate regression in humans. METHODS:
      Epithelial and surrounding stroma cells were micro-dissected from patient
      biopsies obtained before and shortly after castration. IGF-1 mRNA levels were
      quantified by RT-PCR and related to epithelial apoptosis and IGF-1, IGF-1
      receptor, and androgen receptor (AR) immunoreactivity. RESULTS: IGF-1 mRNA was
      principally produced in the stroma and IGF-R1 in the epithelium. Stroma IGF-1
      mRNA levels were significantly decreased after castration in non-malignant but
      not malignant tissue. Lack of stroma IGF-1 reduction after castration was
      associated with low stroma AR expression before therapy. Reduction of IGF-1 mRNA
      levels in the tumor stroma and/or epithelium was associated with epithelial
      apoptosis after therapy. CONCLUSIONS: Low AR expression and maintained stroma IGF
      1 synthesis may result in limited tumor cell death after castration therapy.

PMID- 16998821
TI  - Bayesian sensitivity analysis for unmeasured confounding in observational
      studies.
AB  - We consider Bayesian sensitivity analysis for unmeasured confounding in
      observational studies where the association between a binary exposure, binary
      response, measured confounders and a single binary unmeasured confounder can be
      formulated using logistic regression models. A model for unmeasured confounding
      is presented along with a family of prior distributions that model beliefs about
      a possible unknown unmeasured confounder. Simulation from the posterior
      distribution is accomplished using Markov chain Monte Carlo. Because the model
      for unmeasured confounding is not identifiable, standard large-sample theory for
      Bayesian analysis is not applicable. Consequently, the impact of different
      choices of prior distributions on the coverage probability of credible intervals
      is unknown. Using simulations, we investigate the coverage probability when
      averaged with respect to various distributions over the parameter space. The
      results indicate that credible intervals will have approximately nominal coverage
      probability, on average, when the prior distribution used for sensitivity
      analysis approximates the sampling distribution of model parameters in a
      hypothetical sequence of observational studies. We motivate the method in a study
      of the effectiveness of beta blocker therapy for treatment of heart failure.

PMID- 16998820
TI  - Relaxin becomes upregulated during prostate cancer progression to androgen
      independence and is negatively regulated by androgens.
AB  - BACKGROUND: Relaxin is a potent peptide hormone normally secreted by the
      prostate. This study characterized relaxin expression during prostate cancer
      progression to androgen independence (AI), and in response to androgens. METHODS:
      The prostate cancer cell line, LNCaP, was assayed by microarrays and confirmatory
      Northern analysis to assess changes in relaxin levels due to androgen treatment
      and in LNCaP xenografts following castration. Relaxin protein levels were
      examined by immunohistochemistry (IHC) in tissue microarrays of human prostate
      cancer samples following androgen ablation. RESULTS: Relaxin levels decreased in
      a time and concentration-dependent manner due to androgens in vitro, and
      increased in xenografts post-castration. Relaxin increased in radical
      prostatectomy specimens after 6 months of androgen ablation and in AI tumors, was
      highest in bone metastases. CONCLUSIONS: Relaxin is negatively regulated by
      androgens in vitro and in vivo, which correlates to clinical prostate cancer
      specimens following androgen ablation. The role of relaxin in angiogenesis and
      tissue remodeling suggests it may contribute to prostate cancer progression.

PMID- 16998822
TI  - Detrimental deletions: mitochondria, aging and Parkinson's disease.
AB  - As individuals enter their 80s, they are inevitably confronted with the problem
      of neuronal loss in the brain. The incidence of the common movement disorder
      'mild parkinsonian signs' (MPS) is approximately 50% over the age of 85 years. It
      has long been known that the loss of dopaminergic neurons in the substantia nigra
      pars compacta is a neuropathological hallmark of Parkinson's disease (PD).
      Recently, two papers present clear evidence for a high burden of mitochondrial
      DNA deletions within substantia nigra neurons in aged individuals and individuals
      with PD, pointing towards a common pathway inevitably leading to neuronal
      dysfunction and death.

PMID- 16998823
TI  - Searching for the regulators of human gene expression.
AB  - Many common human traits are believed to be a composite reflection of multiple
      genetic and non-genetic factors and the genetic contribution is consequently
      often difficult to characterise. Recent advances suggest that subtle variation in
      the regulation of gene expression may contribute to complex human traits. In two
      reports, Cheung and colleagues scale up human genetics analysis to an impressive
      level in a genome-wide search for the regulators of gene expression. They perform
      linkage analysis on expression profiles for over 3,500 genes and then employ the
      HapMap resource to take positive findings through to association studies at the
      genome-wide level. This work gives new insights into the complexities of gene
      regulation and the plausibility of genome-wide study design.

PMID- 16998824
TI  - Duplication, divergence and formation of novel protein topologies.
AB  - The rearrangement or permutation of protein substructures is an important mode of
      divergence. Recent work explored one possible underlying mechanism called
      permutation-by-duplication, which produces special forms of motif rearrangements
      called circular permutations. Permutation-by-duplication, involving gene
      duplication, fusion and truncation, can produce fully functional intermediate
      proteins and thus represents a feasible mechanism of protein evolution. In spite
      of this, circular permutations are relatively rare and we discuss possible
      reasons for their existence.

PMID- 16998825
TI  - Non-adaptive evolution of genome complexity.
AB  - Genome complexity is correlated with biological complexity. A recent paper by
      Michael Lynch proposes that evolution of complex genomic architecture was driven
      primarily by non-adaptive stochastic forces, rather than by adaptive evolution.1
      A general negative relationship between selection efficiency and genome
      complexity provides a strong support for this hypothesis. The broad capacity of
      this theory is both its appeal and source for criticism.

PMID- 16998827
TI  - Synthesis of peptide aldehydes.
AB  - The functionalization of peptides and proteins by aldehyde groups has become the
      subject of intensive research since the discovery of the inhibition properties of
      peptide aldehydes towards various enzymes. Furthermore, peptide aldehydes are of
      great interest for peptide backbone modification or ligation reactions. This
      review focuses upon their synthesis, which has been developed following two main
      strategies. The first strategy consists of prior synthesis of the peptide,
      followed by the introduction of the aldehyde function. The second possible
      strategy uses alpha-amino aldehydes as starting materials. After protection of
      the aldehyde, peptide elongation occurs. At the end of the synthesis, the
      aldehyde function can be unmasked.

PMID- 16998826
TI  - Rho GTPase activity zones and transient contractile arrays.
AB  - The Rho GTPases-Rho, Rac and Cdc42-act as molecular switches, cycling between an
      active GTP-bound state and an inactive GDP-bound state, to regulate the actin
      cytoskeleton. It has recently become apparent that the Rho GTPases can be
      activated in subcellular zones that appear semi-stable, yet are dynamically
      maintained. These Rho GTPase activity zones are associated with a variety of
      fundamental biological processes including symmetric and asymmetric cytokinesis
      and cellular wound repair. Here we review the basic features of Rho GTPase
      activity zones, suggest that these zones represent a fundamental signaling
      mechanism, and discuss the implications of zone properties from the perspective
      of both their function and how they are likely to be controlled.

PMID- 16998828
TI  - Of bears, frogs, meat, mice and men: complexity of factors affecting skeletal
      muscle mass and fat.
AB  - Extreme loss of skeletal muscle mass (atrophy) occurs in human muscles that are
      not used. In striking contrast, skeletal muscles do not rapidly waste away in
      hibernating mammals such as bears, or aestivating frogs, subjected to many months
      of inactivity and starvation. What factors regulate skeletal muscle mass and what
      mechanisms protect against muscle atrophy in some species? Severe atrophy also
      occurs with ageing and there is much clinical interest in reducing such loss of
      muscle mass and strength (sarcopenia). In the meat industry, a key aim is
      optimizing the control of skeletal muscle growth and meat quality. The impaired
      response of muscle to insulin resulting in diabetes, that is a consequence of the
      metabolic impact of increasing obesity and fat deposition in humans, is also of
      increasing clinical concern. Intensive research in these fields, combined with
      mouse models, is reviewed with respect to the molecular control of muscle growth
      (myogenesis) and atrophy/hypertrophy and fat deposition (adipogenesis) in
      skeletal muscle, with a focus on IGF-1/insulin signaling.

PMID- 16998829
TI  - Survival curve estimation for informatively coarsened discrete event-time data.
AB  - Interval-censored, or more generally, coarsened event-time data arise when study
      participants are observed at irregular time periods and experience the event of
      interest in between study observations. Such data are often analysed assuming non
      informative censoring, which can produce biased results if the assumption is
      wrong. This paper extends the standard approach for estimating survivor functions
      to allow informatively interval-censored data by incorporating various
      assumptions about the censoring mechanism into the model. We include a Bayesian
      extension in which final estimates are produced by mixing over a distribution of
      assumed censoring mechanisms. We illustrate these methods with a natural history
      study of HIV-infected individuals using assumptions elicited from an AIDS expert.

PMID- 16998830
TI  - Use of hormone replacement therapy before and after ovarian cancer diagnosis and
      ovarian cancer survival.
AB  - Use of hormone replacement therapy (HRT) has been hypothesized to affect survival
      of epithelial ovarian cancer (EOC). We studied 5-year survival in patients with
      invasive EOC and borderline ovarian tumors (BOT) according to HRT use before and
      after diagnosis in a prospective nation-wide cohort study of 799 women diagnosed
      with EOC (n = 649) and BOT (n = 150) aged 50-74 years in 1993-1995 in Sweden. Cox
      regression was used to obtain multivariate age-adjusted hazard ratios (HRs) and
      95% confidence intervals (CIs). Multivariate models included indicator variables
      for age, tumor stage, grade and histological subtype. After 5 years of follow-up,
      45% of the patients with EOC and 93% of the patients with BOT were alive. For
      women with BOT there were no associations between HRT-use pre- or postdiagnosis
      and survival. There was no overall difference in 5-year EOC survival according to
      use HRT before diagnosis (multivariate HR = 0.83, 95% CI = 0.65-1.08), except for
      serous EOC (HR = 0.69, 95% CI = 0.48-0.98). Analyses of different HRT
      preparations, duration and recency of use did not reveal any variations in
      pattern of survival. We observed a better survival for EOC-patients who used HRT
      after diagnosis (multivariate HR = 0.57, 95% CI = 0.42-0.78). We conclude that
      HRT-use prior to diagnosis of EOC does not affect 5-year survival, except for a
      possible survival advantage in serous EOC. Women using HRT after diagnosis had a
      better survival than women with no use, but we cannot rule out that this latter
      finding may reflect a subtle selection process.

PMID- 16998831
TI  - Tumor-stromal cell interaction under hypoxia increases the invasiveness of
      pancreatic cancer cells through the hepatocyte growth factor/c-Met pathway.
AB  - The hypoxic environment in tumor is reported to play an important role in
      pancreatic cancer progression. The interaction between stromal and cancer cells
      also contributes to the malignant behavior of pancreatic cancer. In the present
      study, we investigated whether hypoxic stimulation affects stromal as well as
      pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably
      elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast
      cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells,
      and invasiveness was thus further accelerated when the hypoxic PK8 cells were
      cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic
      conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased
      in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte
      growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met
      phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP
      activity and c-Met phosphorylation of PK8 cells were reduced by the removal of
      HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha
      expression was observed in surrounding stromal as well as pancreatic cancer
      cells, thus indicating hypoxia exists in both of cancer and stromal cells.
      Moreover, the stromal HGF expression was found to significantly correlate with
      not only the stromal HIF-1alpha expression but also the c-Met expression in
      cancer cells. These results indicate that the hypoxic environment within stromal
      as well as cancer cells activates the HGF/c-Met system, thereby contributing to
      the aggressive invasive features of pancreatic cancer.

PMID- 16998832
TI  - Enhanced expression of cholecystokinin-2 receptor promotes the progression of
      colon cancer through activation of focal adhesion kinase.
AB  - Focal adhesion kinase (FAK) is suggested to be intimately involved in the
      progression of malignancies. Our previous research has demonstrated that
      activation of cholecystokinin-2 receptor (CCK2R) by gastrin stimulates a rapid
      activation of FAK pathway in human colon cancer cells. The purpose of this study
      is to determine the role of CCK2R and FAK in the progression of colon cancer. In
      this study, matched tissue samples of primary colon cancer and adjacent normal
      colon mucosa from the same patient were collected from 45 patients with colon
      cancer undergoing surgical resection. The gastrin expression was detected using
      reverse transcription polymerase chain reaction (RT-PCR). The CCK2R expression
      was examined by in situ hybridization and RT-PCR. The expression of FAK and
      phosphorylated FAK at tyrosine 397 (phospho-FAK) were detected using
      immunohistochemistry and immunoblotting. Colo320 and SW787, 2 colon cancer cell
      lines with or without CCK2R expression, were recruited in this study. Antisense
      oligonucleotide of FAK was used to block the expression of FAK. Invasiveness and
      motility of colon cancer cells were detected by Boyden chamber. In this series,
      enhanced expression of gastrin, CCK2R, FAK and phospho-FAK were observed in colon
      cancer tissues. CCK2R expression correlated with expression of phospho-FAK.
      Coexpression of CCK2R and phospho-FAK associated with invasion and lymph node
      metastasis. Increased invasion and motility was induced by gastrin in Colo320
      cells. Overexpression of CCK2R by stable transfection of CCK2R plasmid amplified
      this increase and incubation with 1 microM L-365,260, a specific CCK2R
      antagonist, completely inhibited the effect of gastrin. FAK antisense largely
      blocked the increase of invasion and motility in Colo320 cells. Our data
      represent the evidence for the CCK2R regulating invasion and motility of colon
      cancer cells, and support a role of CCK2R in the progression of colon cancer. FAK
      play a critical role in this CCK2R-mediated effect.

PMID- 16998833
TI  - Soluble N-cadherin in human biological fluids.
AB  - Classical cadherins such as E-, P- and N-cadherin are transmembrane proteins that
      mediate cell-cell adhesion, and are important in embryogenesis, maintenance of
      tissue integrity and cancer. Proteolytic shedding of the extracellular domain
      results in the generation of soluble E-, P- or N-cadherin ectodomains.
      Circulating soluble E- and P-cadherin have been described in the serum, and
      elevated levels were detected in cancer patients when compared with healthy
      persons. Here we report the presence of soluble N-cadherin, a 90-kD protein
      fragment, in the serum of both healthy persons and cancer patients, using a
      direct ELISA and immunoprecipitation. A correlation was found between prostate
      specific antigen and soluble N-cadherin, and significantly elevated levels were
      detected in prostate cancer follow-up patients. The N-cadherin protein is neo
      expressed by carcinomas of the prostate, and is responsible for epithelial to
      fibroblastic transition. This is reflected by the higher concentrations of
      soluble N-cadherin in prostate cancer patients than in healthy persons.

PMID- 16998834
TI  - Endomesoderm specification in Caenorhabditis elegans and other nematodes.
AB  - The endomesoderm gene regulatory network (GRN) of C. elegans is a rich resource
      for studying the properties of cell-fate-specification pathways. This GRN
      contains both cell-autonomous and cell non-autonomous mechanisms, includes
      network motifs found in other GRNs, and ties maternal factors to terminal
      differentiation genes through a regulatory cascade. In most cases, upstream
      regulators and their direct downstream targets are known. With the availability
      of resources to study close and distant relatives of C. elegans, the molecular
      evolution of this network can now be examined. Within Caenorhabditis, components
      of the endomesoderm GRN are well conserved. A cursory examination of the
      preliminary genome sequences of two parasitic nematodes, Haemonchus contortus and
      Brugia malayi, suggests that evolution in this GRN is occurring most rapidly for
      the zygotic genes that specify blastomere identity.

PMID- 16998835
TI  - Pretreatment serum endostatin as a prognostic indicator in metastatic gastric
      carcinoma.
AB  - Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix
      protein collagen XVIII, and is generated by tumor-derived proteases. The presence
      of serum endostatin in patients with gastric cancer has not been reported. The
      authors assessed the serum levels of endostatin in patients with gastric
      carcinoma and evaluated their association with the levels of vascular endothelial
      growth factor (VEGF) and the clinical outcome. A total of 107 patients with
      gastric cancer were included in the study. Pretherapeutic serum levels of
      endostatin and VEGF were measured using an ELISA, and compared with those in 23
      healthy controls. The serum levels of endostatin and VEGF were higher in gastric
      cancer patients than in healthy controls (endostatin, 70.1 +/- 16.6 vs. 52.2 +/-
      6.2 ng/mL [p < 0.001]; VEGF, 55.1 +/- 7.6 vs. 32.1 +/- 2.4 ng/mL [p < 0.001];
      mean +/- SD). Serum endostatin levels were significantly associated with the
      presence of distant metastases (r = 0.556, p < 0.001) and VEGF levels (r = 0.335,
      p < 0.001), but not with the depth of tumor invasion, differentiation, or
      regional lymph node status. A serum endostatin level above the 75th percentile of
      the distribution for the patients (79.2 ng/mL) was associated with a poor outcome
      (last follow-up at 42 months; median survival time, 9 vs. 20 months [log-rank, p
      = 0.017]; median time to progression, 5 vs. 10 months [log-rank, p = 0.022]) in
      the patients with metastatic gastric cancer. The results suggest for the first
      time that an elevated serum level of endostatin at the diagnosis of metastatic
      gastric cancer could be predictive of a poor outcome.

PMID- 16998836
TI  - Bivariate random effect model using skew-normal distribution with application to
      HIV-RNA.
AB  - Correlated data arise in a longitudinal studies from epidemiological and clinical
      research. Random effects models are commonly used to model correlated data.
      Mostly in the longitudinal data setting we assume that the random effects and
      within subject errors are normally distributed. However, the normality assumption
      may not always give robust results, particularly if the data exhibit skewness. In
      this paper, we develop a Bayesian approach to bivariate mixed model and relax the
      normality assumption by using a multivariate skew-normal distribution.
      Specifically, we compare various potential models and illustrate the procedure
      using a real data set from HIV study.

PMID- 16998837
TI  - Extraneuronal roles of cyclin-dependent kinase 5.
AB  - Cyclin-dependent kinase 5 (Cdk5) is recognized as an essential molecule in the
      brain, where it regulates several neuronal activities, including cytoskeletal
      remodeling and synaptic transmission. While activity of Cdk5 has primarily been
      associated with neurons, there are now substantial data indicating that the
      kinase's activity and function are more general. An increasing body of evidence
      has established Cdk5 kinase activity, the presence of the Cdk5 activators, p35
      and p39, and Cdk5 functions in non-neuronal cells, including myocytes, pancreatic
      beta-cells, monocytic and neutrophilic leucocytes, glial cells and germ cells. In
      this review, we present the diverse roles of Cdk5 in several extraneuronal
      paradigms. The unique properties of each of the different cell types appear to
      involve distinct means of Cdk5 regulation and function. The potential mechanisms
      through which Cdk5 regulates extraneuronal cell activities such as exocytosis,
      gene transcription, wound healing and senescence are discussed.

PMID- 16998838
TI  - The rise, fall and renaissance of microsatellites in eukaryotic genomes.
AB  - Microsatellites are among the most versatile of genetic markers, being used in an
      impressive number of biological applications. However, the evolutionary dynamics
      of these markers remain a source of contention. Almost 20 years after the
      discovery of these ubiquitous simple sequences, new genomic data are clarifying
      our understanding of the structure, distribution and variability of
      microsatellites in genomes, especially for the eukaryotes. While these new data
      provide a great deal of descriptive information about the nature and abundance of
      microsatellite sequences within eukaryotic genomes, there have been few attempts
      to synthesise this information to develop a global concept of evolution. This
      review provides an up-to-date account of the mutational processes, biases and
      constraints believed to be involved in the evolution of microsatellites,
      particularly with respect to the creation and degeneration of microsatellites,
      which we assert may be broadly viewed as a life cycle. In addition, we identify
      areas of contention that require further research and propose some possible
      directions for future investigation.

PMID- 16998839
TI  - Checkpoints and restriction points in bacteria and eukaryotic cells.
AB  - Bacterial checkpoints, analogous to those proposed to exist in eukaryotic cells,
      offer insights into the definition of a checkpoint. Examination of bacterial
      "checkpoint" or arrest phenomena illustrate problems with a too-casual
      application of the checkpoint idea to eukaryotic phenomena. The question raised
      here is whether there are cellular processes that "check" whether a cellular
      process is completed. It is possible that many eukaryotic "checkpoints" may not
      have "checking" functions. Some of the ubiquitous checkpoint phenomena widely
      described may be merely the result of the inherent incompleteness of earlier
      events preventing the initiation of subsequent events.

PMID- 16998840
TI  - Prolactin in man: a tale of two promoters.
AB  - The pituitary hormone prolactin (PRL) is best known for its role in the
      regulation of lactation. Recent evidence furthermore indicates PRL is required
      for normal reproduction in rodents. Here, we report on the insertion of two
      transposon-like DNA sequences in the human prolactin gene, which together
      function as an alternative promoter directing extrapituitary PRL expression.
      Indeed, the transposable elements contain transcription factor binding sites that
      have been shown to mediate PRL transcription in human uterine decidualised
      endometrial cells and lymphocytes. We hypothesize that the transposon insertion
      event has resulted in divergent (pituitary versus extrapituitary) expression of
      prolactin in primates, and in differential actions of pituitary versus
      extrapituitary prolactin in lactation versus pregnancy respectively. Importantly,
      the TE insertion might provide a context for some of the conflicting results
      obtained in studies of PRL function in mice and man.

PMID- 16998842
TI  - F-actin involvement in guinea pig sperm motility.
AB  - Sperm motility is a must for natural fertilization to occur. During their travel
      through the epididymis, mammalian spermatozoa gradually acquire the ability to
      move. This is accomplished through a sliding movement of the outer doublet
      microtubules of the axoneme which is energized by the dynein ATPase. Within its
      complex structure, the mammalian sperm flagellum contains F-actin and thus, we
      decided to test in the guinea pig sperm flagellum the role of F-actin in
      motility. During maturation, capacitation, and the acrosome reaction, a gradual
      decrease of the relative concentration of F-actin was observed. Motility
      increased as spermatozoa became able to fertilize. Gelsolin, phalloidin, and KI
      inhibited sperm motility. Gelsolin canceled sperm motility within 20 min of
      treatment while 0.6 M KI had immediate effects. Phalloidin diminished hyperactive
      sperm motility slightly. All three compounds significantly increased the relative
      concentration of F-actin. Latrunculins are conventional drugs that destabilize
      the F-actin cytoskeleton. Latrunculin A (LAT A) did not affect sperm motility;
      but significantly increased F-actin relative concentration. The results suggested
      that in guinea pig spermatozoa, randomly severing F-actin filaments inhibits
      flagellar motility; while end filament alteration does not. Thus, specific
      filament regions seem to be important for sperm motility.

PMID- 16998843
TI  - Differential expression of oxygen-regulated genes in bovine blastocysts.
AB  - Low oxygen conditions (2%) during post-compaction culture of bovine blastocysts
      improve embryo quality, which is associated with a small yet significant increase
      in the expression of glucose transporter 1 (GLUT-1), suggesting a role of oxygen
      in embryo development mediated through oxygen-sensitive gene expression. However,
      bovine embryos to at least the blastocyst stage lack a key regulator of oxygen
      sensitive gene expression, hypoxia-inducible factor 1alpha (HIF1alpha). A second,
      less well-characterized protein (HIF2alpha) is, however, detectable from the 8
      cell stage of development. Here we use differential display to determine
      additional gene targets in bovine embryos in response to low oxygen conditions.
      While development to the blastocyst stage was unaffected by the oxygen
      concentration used during post-compaction culture, differential display
      identified oxygen-regulation of myotrophin and anaphase promoting complex 1
      expression, with significantly lower levels observed following culture under 20%
      oxygen than 2% oxygen. These results further support the hypothesis that the
      level of gene expression of specific transcripts by bovine embryos alters in
      response to changes in the oxygen environment post-compaction. Specifically, we
      have identified two oxygen-sensitive genes that are potentially regulated by HIF2
      in the bovine blastocyst.

PMID- 16998844
TI  - Changes of maternal transcripts in oocytes from persistent follicles in cattle.
AB  - A high incidence of early embryonic loss is associated with prolonged dominance
      of follicles. The objective of the present experiment was to determine if
      persistence of a follicle resulted in alterations in mRNA expression of important
      genes in the oocyte. Cows were assigned to four groups: growing follicles on day
      6 (G0h) or day 8 (G48h) and persistent follicles on day 13 (P0h) or day 15 (P48h)
      of the estrous cycle (estrus = day 0). All cows were super-stimulated on day 1-4.
      Cows in G48h, P0h, and P48h groups received 25 mg prostaglandin (PG) F2alpha on
      day 6. Cows in P0h and P48h groups received progesterone from CIDR-B devices on
      day 5 through 13. Ovaries of cows in G0h, G48h, P0h, and P48h groups were removed
      on day 6, 8, 13, and 15, respectively. Oocytes were aspirated immediately after
      colpotomy and denuded of cumulus cells. Quantitative real-time PCR was used to
      measure the mRNA abundances of 10 selected genes important for early
      embryogenesis in oocytes obtained from growing and persistent follicles. Relative
      abundances of MSY2, PARN, and YY1 mRNA (P < 0.05) were significantly lower in
      oocytes from persistent than from growing follicles. Oocytes from persistent
      follicles, however, had greater abundances of PAP and eIF-4E transcripts (P <
      0.05). The data indicate that persistence of a follicle leads to altered
      abundances of mRNA for genes important for regulation of transcription and
      protein translation in the oocyte, which could compromise development of early
      embryos in cows that ovulate a persistent follicle.

PMID- 16998845
TI  - Generation of viable fish from cryopreserved primordial germ cells.
AB  - An increasing number of wild fish species are in danger of extinction, often as a
      result of human activities. The cryopreservation of gametes and embryos has great
      potential for maintaining and restoring threatened species. The conservation of
      both paternal and maternal genetic information is essential. However, although
      this technique has been successfully applied to the spermatozoa of many fish
      species, reliable methods are lacking for the long-term preservation of fish eggs
      and embryos. Here, we describe a protocol for use with rainbow trout
      (Oncorhynchus mykiss) primordial germ cells (PGCs) and document the restoration
      of live fish from gametes derived from these cryopreserved progenitors. Genital
      ridges (GRs), which are embryonic tissues containing PGCs, were successfully
      cryopreserved in a medium containing 1.8 M ethylene glycol (EG). The thawed PGCs
      that were transplanted into the peritoneal cavities of allogenic trout hatchlings
      differentiated into mature spermatozoa and eggs in the recipient gonads.
      Furthermore, the fertilization of eggs derived from cryopreserved PGCs by
      cryopreserved spermatozoa resulted in the development of fertile F1 fish. This
      PGC cryopreservation technique represents a promising tool in efforts to save
      threatened fish species. Moreover, this approach has significant potential for
      maintaining domesticated fish strains carrying commercially valuable traits for
      aquaculture purposes.

PMID- 16998846
TI  - Sex-specific windows for high mRNA expression of DNA methyltransferases 1 and 3A
      and methyl-CpG-binding domain proteins 2 and 4 in human fetal gonads.
AB  - DNA methyltransferases (DNMTs) and 5-methyl-CpG-binding domain proteins (MBDs)
      are involved in the acquisition of parent-specific epigenetic modifications in
      human male and female germ cells. Reverse Northern blot analyses demonstrated sex
      specific differences in mRNA expression for the maintenance DNMT1 and the de novo
      DNMT3A in developing testis and ovary. In fetal testis DNMT1 and DNMT3A
      expression peaked in mitotically arrested spermatogonia around 21 weeks
      gestation. In fetal ovary transcriptional upregulation of DNMT1 and DNMT3A
      occurred during a very brief period at 16 weeks gestation, when the oocytes
      proceeded through meiotic prophase. Fetal gonads showed several fold higher
      DNMT3A expression levels than fetal brain and adult tissues. The most abundant
      DNMT3A isoform in fetal testis and ovary was DNMT3A2, whereas in all other
      analyzed tissues DNMT3A1 predominated. The catalytically inactive DNMT3A3 isoform
      was also present at relatively high levels in developing gonads and may perform a
      regulatory function(s). In both male and female fetal gonads expression of genes
      for MBD2 and MBD4, which may be implicated in chromatin remodeling of methylated
      genomic DNA sequences, was tightly linked to DNMT expression. We propose that the
      sex-specific time windows for concomitant upregulation of DNMT1, DNMT3A, MBD2,
      and MBD4 are associated with prenatal remethylation of the human male and female
      germ line.

PMID- 16998847
TI  - Computer-aided meiotic maturation assay (CAMMA) of zebrafish (danio rerio)
      oocytes in vitro.
AB  - We have developed a new technique called Computer-Aided Meiotic Maturation Assay
      (CAMMA) for imaging large arrays of zebrafish oocytes and automatically
      collecting image files at regular intervals during meiotic maturation. This novel
      method uses a transparency scanner interfaced to a computer with macro
      programming that automatically scans and archives the image files. Images are
      stacked and analyzed with ImageJ to quantify changes in optical density
      characteristic of zebrafish oocyte maturation. Major advantages of CAMMA include
      (1) ability to image very large arrays of oocytes and follow individual cells
      over time, (2) simultaneously image many treatment groups, (3) digitized images
      may be stacked, animated, and analyzed in programs such as ImageJ, NIH-Image, or
      ScionImage, and (4) CAMMA system is inexpensive, costing less than most
      microscopes used in traditional assays. We have used CAMMA to determine the dose
      response and time course of oocyte maturation induced by 17alpha
      hydroxyprogesterone (HP). Maximal decrease in optical density occurs around 5 hr
      after 0.1 micro g/ml HP (28.5 degrees C), approximately 3 hr after germinal
      vesicle migration (GVM) and dissolution (GVD). In addition to changes in optical
      density, GVD is accompanied by streaming of ooplasm to the animal pole to form a
      blastodisc. These dynamic changes are readily visualized by animating image
      stacks from CAMMA; thus, CAMMA provides a valuable source of time-lapse movies
      for those studying zebrafish oocyte maturation. The oocyte clearing documented by
      CAMMA is correlated to changes in size distribution of major yolk proteins upon
      SDS-PAGE, and, this in turn, is related to increased cyclin B(1) protein.

PMID- 16998848
TI  - Transcription profile in mouse four-cell, morula, and blastocyst: Genes
      implicated in compaction and blastocoel formation.
AB  - To gain insight into early embryo development, we utilized microarray technology
      to compare gene expression profiles in four-cell (4C), morula (MO), and
      blastocyst (BL) stage embryos. Differences in spot intensities were normalized,
      and grouped by using Avadis Prophetic software platform (version 3.3, Strand
      Genomics Ltd.) and categories were based on the PANTHER and gene ontology (GO)
      classification system. This technique identified 622 of 7,927 genes as being more
      highly expressed in MO when compared to 4C (P < 0.05); similarly, we identified
      654 of 9,299 genes as being more highly expressed in BL than in MO (P < 0.05).
      Upregulation of genes for cytoskeletal, cell adhesion, and cell junction proteins
      were identified in the MO as compared to the 4C stage embryos, this means they
      could be involved in the cell compaction necessary for the development to the MO.
      Genes thought to be involved in ion channels, membrane traffic, transfer/carrier
      proteins, and lipid metabolism were also identified as being expressed at a
      higher level in the BL stage embryos than in the MO. Real-time RT-PCR was
      performed to confirm differential expression of selected genes. The
      identification of the genes being expressed in here will provide insight into the
      complex gene regulatory networks effecting compaction and blastocoel formation.

PMID- 16998849
TI  - Impact of in vitro production techniques on the expression of X-linked genes in
      bovine (bos taurus) oocytes and pre-attachment embryos.
AB  - Our previous studies showed that expression patterns of X-linked genes in
      cultured cells are different from those of their tissues of origin. This
      investigation analyses the transcription pattern of the X-linked genes BIRC4,
      GAB3, MECP2, RPS4X, SLC25A6, and XIST in bovine in vitro matured oocytes and in
      vitro fertilized embryos, and their in vivo counterparts. In vitro-derived pools
      of mature oocytes and pre-attachment embryos were obtained by: (a) TCM-199/serum
      with bovine oviductal epithelial cells as co-culture, and (b) synthetic oviductal
      fluid/BSA. Pools of in vivo-derived morulae and blastocysts were provided by a
      commercial embryo transfer operation. Total RNA was extracted for quantification
      of gene-specific transcript levels using real-time quantitative PCR. Statistical
      analysis was performed using a mixed model factorial ANOVA with alpha = 0.05. The
      effect of the in vitro environmental conditions on X-linked gene transcription
      was most evident during the fourth cell cycle, at the period of activation of the
      embryonic genome, and seemed to be less pronounced at later developmental stages,
      with the exception of BIRC4. The levels of X-linked genes transcripts in in vivo
      derived embryos were lower relative to their in vitro counterparts for all genes
      tested. Finally, the pattern of expression of XIST in bovine oocytes and embryos
      was similar to that reported in humans. These results highlight the possibility
      that X-linked gene expression analysis is a useful tool to monitor the impact of
      reproductive biotechnologies on the developmental potential of embryos and aid in
      their improvement.

PMID- 16998850
TI  - Transferrin overexpression alters testicular function in aged mice.
AB  - Many studies have shown a correlation between transferrin (Tf) concentration and
      sperm yield in several mammalian species. We have used transgenic mice expressing
      human Tf (hTf) to investigate if overexpression of Tf increases the efficiency of
      mouse spermatogenesis. We demonstrated that a 36% increase of Tf does not
      ameliorate the efficiency of mouse spermatogenesis but on the contrary resulted
      in a 36% decrease of testis sperm reserves. Tf overexpression had no effect on
      testicular determination and development, however testicular function of these
      transgenic mice was affected in an age-dependent manner. At 16 months of age,
      testicular and epididymal weights were significantly reduced. While
      spermatogenesis was qualitatively normal, testicular functions were perturbed. In
      fact, testosterone rate after human chorionic gonadotropin (hCG) stimulation was
      lower in Tf overexpressing mice. Intratesticular concentration of estradiol
      17beta was increased and fluid accumulation after ligation of rete testis was
      more abundant in these transgenic mice. Surprisingly, we found that endogenous Tf
      levels were also increased in Tf overexpressing mice and we demonstrated for the
      first time that Tf may serve to upregulate its own expression in testis.
      Collectively, our data show that Tf overexpression has negative effects on
      testicular function and that Tf levels require strict regulation in the testis.

PMID- 16998851
TI  - Plasticity of epidermal adult stem cells derived from adult goat ear skin.
AB  - Here we report the isolation and characterization of pluripotent stem cells from
      adult goat skin. We found that these primary cells have the properties of
      embryonic stem cells (ESC), including the expression of appropriate immunological
      markers and the capability of forming embryoid bodies. The subcultured cells also
      show the characteristics of stem cells, such as the expression of CK19, beta(1
      )integrin, P63, and formation of holo-clones in culture. Therefore, we termed
      these cells epidermal adult stem cells (EpiASC), although their origin was not
      identified. We have shown that clones of individual EpiASC proliferate and
      differentiate in culture to produce neurons, cardiomyocytes, osteoblasts, and
      occytes. Further, we cultivated EpiASC on bioengineered dermis and denuded human
      amniotic membrane (HAM), to reconstruct artificial skin and corneal epithelium.
      We successfully transplanted those artificial tissues in goats with acute full
      thickness skin defect (AFTSD) and limbal stem cell deficiency (LSCD),
      respectively. Our results showed that indeed EpiASC reconstructed the skin (hair
      was observed in restored areas), and repaired the damaged cornea of goats with
      total LSCD. These data confirm that EpiASC can differentiate into different
      functional cell types in vivo or in vitro. Due to their high degree of inherent
      plasticity, and to their easy accessibility for collection from the skin, EpiASC
      are excellent candidate sources for diverse cell therapies.

PMID- 16998852
TI  - Safety of endobronchial biopsy in children with cystic fibrosis.
AB  - There is little found in the published literature regarding the use of
      endobronchial biopsy (EBB) in children with cystic fibrosis (CF). One concern
      over the use of the technique may relate to safety, in particular increased risk
      of bleeding from a hypertrophied bronchial circulation. The aim of this
      retrospective study was to compare the safety of EBB in children with CF and
      those with other conditions, the most frequent of which included primary ciliary
      dyskinesia and recurrent lower respiratory tract infections. Case notes of all
      children undergoing EBB in our institution between February 2003 and May 2004
      were reviewed. EBB was performed during 45 bronchoscopies in 42 CF patients (19
      males, group mean age 7.13 +/- 4.48 years) and in 39 controls (20 males, group
      mean age 6.59 +/- 4.48 years). There were no significant differences between
      disease groups in the number, type, or severity of complications occurring during
      or in the first 12 hr after the procedure. We conclude that EBB performed as part
      of fibreoptic bronchoscopy (FOB) under general anaesthesia can be performed
      safely in children with CF, when both bronchoscopist and anaesthetist are
      suitably experienced. Studies of such samples would allow us to determine the
      early pathological changes in the CF airway and possibly find new treatments to
      prevent the progression to bronchiectasis and end stage airway destruction.

PMID- 16998853
TI  - Pitfalls in non-therapeutic research in children.
AB  - Research has brought significant medical advances in modern times benefiting
      virtually all people. Children as a class should not be excluded from research
      studies. However, non-therapeutic research is potentially problematic in children
      because they must be afforded special protection from harm and exploitation by
      care-givers, researchers, and institutional review boards. An article in this
      month's journal provides an opportunity for a systematic analysis using the
      methodology provided by the United States Code of Federal Regulations. The
      research design of this particular study does not appear to stand up to the
      requirements of the Code.

PMID- 16998854
TI  - Molecular identities of human sperm proteins reactive with antibodies in sera of
      immunoinfertile women.
AB  - Antisperm antibodies (ASA) can cause infertility in both men and women. It is
      important to delineate the sperm antigens against which these ASA are directed.
      Sperm proteins were separated by 2D gel electrophoresis and transferred to
      nitrocellulose membrane and incubated with sera from fertile women or
      immunoinfertile women having ASA. The corresponding immunoreactive peptide spots
      were cored from the gel and analyzed by the two-dimensional (2D) gel
      electrophoresis/matrix-assisted laser desoprtion ionization-time of flight-mass
      spectrometry and liquid chromatography-mass spectrometry (MALDI-TOF-MS/LC-MS). A
      total of 68 spots belonging to 38 different proteins and their isomers were
      identified. Fourteen of these proteins and their isomers reacted with both the
      fertile and immunoinfertile sera. Twenty-four of these proteins reacted
      specifically only with the immunoinfertile sera and not with the fertile sera.
      Among them was a novel protein designated as a hypothetical protein FLJ32704
      (accession # Q96MA6). An immunodominant sequence (amino acid 151-159) of this
      protein was identified and a nonamer peptide based upon this sequence (IQTLG1TPR)
      was synthesized and examined for its immunoreactivity. This synthetic peptide
      reacted with 90% (36/40) of immunoinfertile sera and not with any of the fertile
      sera (0/40) in the enzyme-linked immnosorbent assay (ELISA). In conclusion, using
      the 2D gel electrophoresis/MALDI-TOF-MS/LC-MS procedure, we have identified
      several known and at least one novel antigen against which the antibodies are
      present in sera of immunoinfertile but not fertile women. Some of these antigens
      may find applications in specific diagonsis and treatment of
      infertility/immunoinfertility, and in the development of new generation of
      contraceptive modalities including contraceptive vaccines.

PMID- 16998855
TI  - Amino acids in oviduct and uterine fluid and blood plasma during the estrous
      cycle in the bovine.
AB  - Up to 40% of cattle embryos die within 3 weeks of fertilization while they are
      nutritionally dependent on the maternal environment provided by the oviduct and
      uterine fluids for their development and survival. Despite this dependence there
      is limited information on the composition of these fluids in cattle. Amino acids
      are essential for the normal growth and development of the early embryo, acting
      as precursors of proteins and nucleic acids and as energy sources, osmolytes and
      signaling molecules. The objective of this study was to measure and compare the
      amino acid concentrations of oviduct and uterine fluid and blood plasma on
      different days of the estrous cycle. Oviduct fluid was collected in situ from
      anaesthetised heifers on Days 0, 2, 3, 4 and 6 and uterine fluid on Days 6, 8 and
      14 of the estrous cycle and the concentrations of 19 amino acids determined.
      Glycine was the most abundant amino acid in both oviduct and uterine fluid.
      However, the concentrations of many amino acids differed between oviduct and
      uterus and many were present at higher concentrations in oviduct and uterine
      fluid than in blood plasma. Oviduct fluid concentrations of amino acids were not
      affected by day of cycle in contrast to uterine fluid for which there was a day
      of cycle effect on most of the amino acids. These results provide novel
      information on the amino acid concentrations in the maternal environment of the
      early cattle embryo and could form the basis for devising improved media for the
      production of embryos in vitro.

PMID- 16998856
TI  - Impact of proximity to comprehensive sickle cell center on utilization of
      healthcare services among children with sickle cell disease.
AB  - BACKGROUND: The impact of comprehensive care on utilization of healthcare
      services by children with sickle cell disease (SCD) has not been fully evaluated.
      We compared the medical care utilization and mortality in children less than 20
      years of age with SCD in four regions in the state of Tennessee with and without
      a comprehensive sickle cell center (CSCC). METHODS: Rates of hospitalizations,
      outpatient and emergency department (ED) visits, and deaths were measured in a
      cohort of children aged <20 years with SCD, enrolled in TennCare, from January
      1995 to December 2002. TennCare data linked to Tennessee vital records were used
      to define the population and identify the outcomes. The patients were classified
      into one of four regions based on their residential address on the day of their
      hospitalization or outpatient visit. RESULTS: The cohort consisted of 1,214
      children with 6,393 person-years of follow-up. Fifty-six percent of patients
      resided in the region with the CSCC. This region had the highest overall rates of
      hospitalization for all children (P < 0.001), while ED and outpatient visits were
      higher in other areas. The death rates ranged from 1.8 to 4.3 per 1,000 person
      years in the four regions and did not represent statistically significant
      differences. CONCLUSION: No clear pattern of improved utilization of medical care
      services were identified in relation to proximity of residence to a CSCC. This
      cohort was not large enough to detect small differences in death rates. In
      addition, other outcomes that incorporate quality of life measures may be more
      sensitive to differences in medical care.

PMID- 16998857
TI  - Oxidative stress reduces the muscarinic receptor function in the urinary bladder.
AB  - AIMS: Several pathophysiological conditions in the urinary bladder, for example,
      ischemia/reperfusion and inflammation are characterized by the formation of
      reactive oxygen species (ROS). The ROS are highly toxic because they can destroy
      proteins, DNA, and lipids. The aim of this study was to investigate the effect of
      oxidative stress on excitation-contraction coupling of detrusor smooth muscle.
      MATERIALS AND METHODS: Smooth muscle strips were dissected from pig urinary
      bladder and mounted in organ baths. Oxidative stress was mimicked by the addition
      of Cumene hydroperoxide (CHP), a lipophilic hydroperoxide, to the organ baths.
      Contractile responses to electrical field stimulation (EFS: 4-32 Hz), carbachol
      (10(-8)-3 x 10(-5) M), potassium (65.3 mM), and ATP (1 mM) were monitored before
      and after the addition of CHP. RESULTS: Responses of detrusor strips to EFS were
      for the greater part based on neurogenic stimulation and the release of
      acetylcholine. CHP diminished contractile responses to EFS and carbachol to the
      same extent. The pD(2) value of the carbachol concentration-response curve
      decreased significantly after exposure to 0.1 mM, 0.4 mM, 0.8 mM CHP. Furthermore
      the maximal effect obtained with carbachol was significantly reduced after 0.1
      mM, 0.4 mM, and 0.8 mM CHP treatment. Contractions induced by potassium and ATP
      were significantly less affected by oxidative stress compared to EFS- and
      carbachol-induced responses of comparable amplitude. CONCLUSIONS: The results of
      our study demonstrate that oxidative stress induced by CHP affects pig bladder
      contractility. The muscarinic receptor signaling system is severely damaged. L
      type calcium channels and the contractile system are less affected and
      cholinergic nerves remain largely unaffected.

PMID- 16998858
TI  - Preoperative erectile function is one predictor for post prostatectomy
      incontinence.
AB  - AIMS: The precise etiology of post prostatectomy incontinence (PPI) is not fully
      understood and risk factors are not yet comprehensively defined. It has been
      reported that sparing of the neurovascular bundle during prostatectomy improves
      postoperative erectile function, whereas the influence on urinary control is
      unclear. From daily clinical experience we made the impression that patients who
      are in the best shape have better erections and better continence. We therefore
      searched our database for a possible correlation between the preoperative
      erectile function and the incidence of PPI. PATIENTS AND METHODS: Four hundred
      three patients who underwent radical retropubic prostatectomy between January
      2000 and May 2003 were enrolled into this retrospective study. Data of 327
      patients (response rate 81%) at a median follow-up of 26 months were analyzed
      using the validated International Index of Erectile Function (IIEF 5), the
      validated Urinary Distress Inventory (UDI6) and a standardized urinary symptom
      inventory. Continence was defined as usage of no or one pad daily. Erectile
      Dysfunction (ED) was defined as none/mild or moderate/severe with an IIEF 5 score
      of 17 or more or less than 17, respectively. RESULTS: Univariate and mulitvariate
      logistic regression analysis including preoperative IIEF 5 scores, age and nerve
      sparing prostatectomy, identified preoperative erectile function as significant
      predictor for PPI (P = 0.024), whereas age (P = 0.759) and nerve sparing
      prostatectomy (P = 0.504) did not predict PPI. CONCLUSION: Erectile function is a
      predictor of PPI and should be recorded preoperatively.

PMID- 16998859
TI  - Clinical usefulness of urodynamic assessment for maintenance of bladder function
      in patients with spinal cord injury.
AB  - AIMS: The vast majority of spinal cord lesions cause neurogenic bladder
      disorders. Detrusor hyperreflexia presents a major risk factor for renal damage
      in these patients. We evaluated the long-term results of patients with spinal
      cord injury treated at our institution. METHODS: Eighty spinal cord injury
      patients (60 male, 20 female; mean age 29.6 years) with at least one follow-up
      visit a year for a minimum of five consecutive years, were included in this
      retrospective analysis. Follow-up included urodynamic evaluation, sonography of
      the upper and lower urinary tract, urine examination, and evaluation of renal
      function. Treatment modifications were based on the urodynamic findings. RESULTS:
      Mean follow-up was 67.3 months (range 60-103 months). At initial presentation, 51
      patients performed intermittent catheterization, 7 had indwelling catheters, 10
      utilized reflex voiding, 2 patients presented with a Brindley stimulator, 10
      patients used abdominal straining. At the end of our study, no patient had signs
      of renal damage. To achieve that goal, 8 patients underwent sphincterotomy, 3
      received a Brindley stimulator, 3 underwent bladder augmentation, one Kock pouch
      was performed, and 12 patients were treated with botulinum-A-toxin injections in
      the detrusor. Twenty-two patients received intravesical anticholinergic therapy.
      In merely three patients, treatment was not modified during the entire follow-up.
      CONCLUSIONS: In the long term, treatment strategy of neurogenic bladder
      dysfunction in patients with spinal cord injury had to be modified in almost all
      patients. 18.8% underwent surgery. For protection of the upper urinary tract and
      maintenance of continence, regular urodynamic follow-up is warranted.

PMID- 16998860
TI  - Long-term patient satisfaction following cadaveric pubovaginal sling incontinence
      surgery using the UDI and IIQ-7 questionnaires.
AB  - AIMS: The goal of any incontinence surgery is overall long-term patient
      satisfaction. The purpose of our study was to assess long-term patient
      satisfaction following cadaveric fascia lata pubovaginal sling surgery using the
      urogenital distress inventory (UDI) and the short form of the incontinence impact
      questionnaire (IIQ-7). MATERIALS AND METHODS: A total of 47 patients who
      underwent pubovaginal sling incontinence surgery with a minimum follow-up of 2
      years were sent by mail the UDI (total score = 300) and the IIQ-7 (total score =
      100). Thirty-seven responses (78.7%) were obtained, with a mean follow-up of 3.8
      years (range 2.0-6.2). RESULTS: Of the 37 patients who responded, the mean UDI
      score was 75.8 and the mean IIQ-7 score was 21.4. There was no difference in the
      mean IIQ-7 score for patients with more than 4 years follow-up as compared to the
      entire group (28.8, P = 0.22). In contrast, the mean UDI score for patients with
      more than 4 years follow-up was greater compared to the entire group (99.1, P =
      0.04). UDI subscale analysis revealed that patients mainly complained of both
      irritative and stress symptoms as opposed to obstructive/discomfort symptoms (P <
      0.01). Patients with pre-operative mixed incontinence had greater mean UDI and
      IIQ-7 scores compared to patients with pre-operative pure stress incontinence
      (96.7 vs. 58.0, P = 0.04; 32.5 vs. 11.9, P = 0.03). CONCLUSIONS: Overall long
      term scores assessing quality of life (IIQ-7) were good and those assessing
      symptom distress (UDI) were satisfactory following pubovaginal sling surgery.
      Patients with pre-operative mixed incontinence are at greatest risk for post
      operative dissatisfaction.

PMID- 16998861
TI  - Which questionnaire? A psychometric evaluation of three patient-based outcome
      measures used to assess surgery for stress urinary incontinence.
AB  - AIMS: The aim of the study was to further validate three patient-based outcome
      measures (PBOM) used to assess the outcome of surgery for stress urinary
      incontinence and to compare their psychometric properties with a view to
      determining the most appropriate measure for clinical use. METHODS: The work was
      embedded within a randomized controlled trial of laparoscopic and open
      colposuspension. The trial recruited 291 women from six centers. The three
      instruments compared were Bristol Female Lower Urinary Tract Symptom
      Questionnaire (BFLUTS), Kings Health Questionnaire (KHQ), and the Symptom
      Severity Index and Symptom Impact Index (SSI/SII). The International Consultation
      on Incontinence (ICI) ABC grading system of psychometric propertie's reliability,
      validity, and responsiveness was used to evaluate the instruments. RESULTS: From
      the analysis of the psychometric properties of the three instruments, the SSI/SII
      appeared to have the best psychometric profile; Grade A, BFLUTS was of grade A,
      and KHQ was of grade B. SSI/SII had a good degree of internal consistency
      (Cronbach's alpha 0.74-0.78). BFLUTS and KHQ both had domains in which the
      internal consistency was <0.7. The SSI domain of the SSI/SII was the only domain
      to correlate to the 1-hr pad test. All domains of the SSI/SII were able to
      distinguish those cured from not cured and it was most responsive to change.
      Unlike the KHQ, the SSI/SII had no significant ceiling or floor effects.
      CONCLUSIONS: This study has demonstrated that when instruments are used in
      different populations their psychometric properties may change. All three
      instruments analyzed had limitations when used as an outcome measure for surgery
      for stress urinary incontinence.

PMID- 16998862
TI  - The natural history of overactive bladder and stress urinary incontinence in
      older women in the community: a 3-year prospective cohort study.
AB  - AIMS: This is the first study designed to describe the natural history of stress
      urinary incontinence (SUI) and overactive bladder (OAB), using validated symptom
      syndrome severity scores developed for the purpose. METHODS: Two separate but
      related studies were involved, (i) a clinic sample (N = 2,052) from a randomised
      controlled trial (RCT) and (ii) a prospective cohort study (N = 12,750) with 3
      year follow-up. Subjects in both studies were women aged 40 or more living in the
      community, approached using similar postal questionnaires. Severity scores using
      standardised urinary symptoms were derived for SUI and OAB from weightings
      obtained from logistic regression models of symptoms in relation to urodynamic
      diagnosis. Symptom severity scores were plotted for baseline and 3 years of
      follow-up to demonstrate the natural history of the main categories of SUI and
      OAB. RESULTS: Overactive bladder and SUI syndrome severity scores showed good
      criterion validity in relation to relevant clinical measures and good test-retest
      reliability. OAB severity increased progressively with age including a period of
      accelerated increase in the 60s. In contrast, SUI severity showed two age-related
      peaks around age 60 and again at age 80. SUI severity also showed a more
      fluctuating pattern from year to year compared to OAB. CONCLUSIONS: Contrasting
      patterns of natural history for OAB and SUI syndromes were identified consistent
      with differences in the patterns of related co-morbidities. Further studies are
      needed to confirm these findings.

PMID- 16998863
TI  - Effects of 138-355, a beta3-adrenoceptor selective agonist, on relaxation of the
      human detrusor muscle in vitro.
AB  - AIMS: Beta-adrenoceptors are the predominant beta-adrenoceptor subtype present in
      the bladder and urethra. This study investigates the effects of 138-355, an
      active-metabolite of TT-138 and beta(3)-adrenoceptor agonist, on relaxation of
      the human detrusor in vitro. METHODS: Tumor-free tissue samples of human bladder
      muscle from 39 patients undergoing total cystectomy due to bladder cancer were
      obtained, and the mucosa and serosa were removed. Tissues were mounted in 5 or 10
      ml organ baths containing Krebs solution, which was gassed with 95% O(2) and 5%
      CO(2). Resting tension of 1 g was obtained. When the contraction had stabilized,
      increasing concentrations of beta adrenoceptor agonists (non-selective,
      isoprenaline; beta(2)-selective, clenbuterol; beta(3)-selective, 138-355 and
      BRL37344) and propiverine (a non-selective anti-muscarinic antagonist) were added
      cumulatively and concentration-relaxation curves (CRCs) were obtained. CRCs to
      138-355 were obtained in the absence and presence of SR59230A, a beta(3)
      selective antagonist, and antagonist affinity values (pA(2)) were calculated from
      the Schild plot. RESULTS: Isoproterenol, clenbuterol, 138-355 and BRL37344
      concentration-dependently relaxed isolated human urinary bladder strips with
      pEC(50) value being 6.76+/-0.17, 5.23+/-0.22, 5.80+/-0.26 and 5.90+/-0.28,
      respectively. Following antagonist assay, it was observed that concentration
      relaxation curves to 138-355 was competitively antagonized by beta(3)-
      adrenoceptor antagonist, SR59230A, with a pA(2) value of 7.01+/-0.45 and with a
      Schild slope of 0.72+/-0.07. CONCLUSIONS: Involvement of the beta(3)-adrenoceptor
      appears to be greater than that of the beta(3)-adrenoceptor for relaxations of
      the human bladder. The relaxation response of 138-355 appears to be mediated via
      the beta(3)-adrenoceptor stimulation.

PMID- 16998864
TI  - Glutathione peroxidase 1 and a high cellular glutathione concentration are
      essential for effective organic hydroperoxide detoxification in astrocytes.
AB  - Organic hydroperoxides are produced in the eicosanoid metabolism and by lipid
      peroxidation. To examine the contribution of glutathione peroxidase-1 (GPx1) and
      glutathione (GSH) in the disposal of organic hydroperoxides in brain astrocytes,
      primary astrocyte cultures from wild type or GPx1-deficient (GPx1(-/-)) mice were
      exposed to cumene hydroperoxide (CHP). After application of 100 microM CHP, the
      peroxide disappeared quickly from the incubation medium of wild type cells with a
      half-life of 9 min, whereas CHP clearance was strongly retarded in GPx1(-/-)
      astrocytes. Depletion of GSH by pre-incubation with buthionine sulfoximine (BSO)
      significantly slowed CHP clearance by wild type astrocytes, while almost
      completely preventing peroxide disposal by GPx1(-/-) cells. In contrast, the
      catalase inhibitor 3-aminotriazole (3AT) had no effect on CHP clearance.
      Application of CHP to wild type astrocytes was followed by a rapid and transient
      accumulation of GSSG, whereas in GPx1(-/-) cells no increase in the GSSG content
      was detected. Astrocytes from both mouse lines remained viable for up to 24 h
      following CHP exposure, however depletion of cellular GSH by pre-treatment with
      BSO compromised the viability of astrocytes, an effect that was stronger in GPx1(
      /-) than in wild type cells. This cell death was almost completely prevented by
      iron chelators, whereas pre-incubation with iron increased CHP toxicity. These
      novel data demonstrate that the toxicity of organic hydroperoxides in astrocytes
      is iron-mediated, and that an intact GSH system is required for the effective
      removal of organic hydroperoxides and for protection from these peroxides.

PMID- 16998865
TI  - Statins induce differentiation and cell death in neurons and astroglia.
AB  - Statins are potent inhibitors of the hydroxy-methyl-glutaryl-coenzyme A
      reductase, the rate limiting enzyme for cholesterol biosynthesis. Experimental
      and clinical studies with statins suggest that they have beneficial effects on
      neurodegenerative disorders. Thus, it was of interest to characterize the direct
      effects of statins on CNS neurons and glial cells. We have treated defined
      cultures of neurons and astrocytes of newborn rats with two lipophilic statins,
      atorvastatin and simvastatin, and analyzed their effects on morphology and
      survival. Treatment of astrocytes with statins induced a time- and dose-dependent
      stellation, followed by apoptosis. Similarly, statins elicited programmed cell
      death of cerebellar granule neurons but with a higher sensitivity. Analysis of
      different signaling cascades revealed that statins fail to influence classical
      pathways such as Akt or MAP kinases, known to be activated in CNS cells. In
      addition, astrocyte stellation triggered by statins resembled dibutryl-cyclic AMP
      (db-cAMP) induced morphological differentiation. However, in contrast to db-cAMP,
      statins induced upregulation of low-density lipoprotein receptors, without
      affecting GFAP expression, indicating separate underlying mechanisms. Analysis of
      the cholesterol biosynthetic pathway revealed that lack of mevalonate and of its
      downstream metabolites, mainly geranylgeranyl-pyrophosphate (GGPP), is
      responsible for the statin-induced apoptosis of neurons and astrocytes. Moreover,
      astrocytic stellation triggered by statins was inhibited by mevalonate and GGPP.
      Interestingly, neuronal cell death was significantly reduced in astrocyte/neuron
      co-cultures treated with statins. We postulate that under these conditions
      signals provided by astrocytes, e.g., isoprenoids play a key role in neuronal
      survival.

PMID- 16998866
TI  - Single and three-color flow cytometry assay for intracellular zinc ion
      availability in human lymphocytes with Zinpyr-1 and double immunofluorescence:
      relationship with metallothioneins.
AB  - BACKGROUND: : The amount of available intracellular zinc is pivotal to regulate
      many cellular processes, including oxidative stress response and apoptotic
      mechanisms. Therefore it is not surprising that zinc homeostasis and
      dyshomeostasis is involved in many physiological and pathological states,
      respectively. Cell permeable zinc probes allow intracellular applications with
      microscopy technology, but flow cytometry (FC) applications have been scarcely
      explored, albeit they can be suited to study zinc homeostasis in different cell
      types, including rare cells. METHODS: : We describe a FC method able to estimate
      intracellular zinc ion availability and the intracellular capability to activate
      a zinc signal after treatment with an NO-donor (AcOM-DEA/NO) in human PBMCs,
      using the fluorescent zinc-specific probe, Zinpyr-1 (ZP1), alone or in
      association with CD4-PE and CD8-Cychrome mAb. RESULTS: : This method was able to
      detect an increase/decrease of intracellular zinc available in human fresh
      cultured PBMC and in immune subsets using AcOM-DEA/NO or TPEN, respectively. ZP1
      mean fluorescence on gated histograms was sensitive to the amount of zinc added
      in the culture medium and significantly correlated to metallothioneins and total
      intracellular zinc. CONCLUSIONS: : FC applications using ZP1 may be a fast and
      useful tool to study zinc homeostasis in immune cells.

PMID- 16998867
TI  - Flow cytometry for assessment of the efficacy of siRNA.
AB  - BACKGROUND: Small interfering RNA (siRNA) has emerged as a powerful tool to study
      the loss-of-function phenotype by specifically silencing a target gene. The
      success of gene silencing depends on the choice of appropriate target sequence,
      and requires a rapid and sensitive assay for quantifying siRNA efficiency.
      Conventional assays include Western blotting and reverse transcription coupled
      with polymerase chain reaction. However, these methods are somewhat inaccurate
      owing to the variation in transfection efficiency. To avoid this, we have
      developed a flow cytometric method to provide a quantitative analysis of siRNA
      efficacy. METHODS: We constructed a novel vector pHyper1G, which can express
      enhanced green fluorescent protein (EGFP). It contains a H1 promoter, which can
      drive expression of short hairpin RNA (shRNA) directed against a target gene. The
      target gene was cloned into pDsRed1-N1. The resulting construct can express a
      fusion protein between target protein and DsRed. These vectors were co
      transfected into 293T cells. The transfected cells were analyzed by flow
      cytometry. The percentage of EGFP+, DsRed+ cells and the change in mean
      fluorescence intensity (MFI) of DsRed channel indicate changes in expression of
      target gene in a cell population, and hence the efficacy of the corresponding
      shRNA. In addition, the cells transfected with pHyper1G derivative were sorted,
      and analyzed for the activity of target gene. RESULTS: We designed an
      oligonucleotide duplex encoding shRNA against glucose-6-phosphate dehydrogenase
      (G6PD) gene, and cloned this into pHyper1G. The resulting vector pHyper1G101
      effectively knocked down the expression of G6PD-DsRed from pDsRed301, as shown by
      significant reduction in both the percentage of EGFP+, DsRed+ cells, and MFI.
      Changes in these parameters were consistent with decreases in protein level and
      activity of G6PD. Moreover, albeit at low suboptimal transfection efficiency,
      cells transfected with pHyper1G101 alone were successfully sorted for those
      expressing shRNA, and their G6PD activity was found to be suppressed. CONCLUSION:
      Flow cytometric analysis provides a reliable assessment of the efficiency of
      siRNA in a cell population. This method can be easily automated and used for
      screening of appropriate shRNAs against certain genes. Moreover, using the
      present system, we can deliberately sort for and analyze those cells expressing
      shRNA. This can be applied to the hard-to-transfect cell types, and greatly
      facilitates the analyses of gene silencing in these cells.

PMID- 16998868
TI  - Flow cytometric method for the assessment of the minimal inhibitory
      concentrations of antibacterial agents to Mycoplasma agalactiae.
AB  - In this study, flow cytometry was evaluated for the determination of the minimal
      inhibitory concentrations (MIC) of seven antibacterial agents (enrofloxacin,
      ciprofloxacin, gentamicin, streptomycin, chloramphenicol, oxytetracycline, and
      tylosin) on Mycoplasma (M.) agalactiae. Flow cytometry was able to detect M.
      agalactiae inhibition from 6 h postincubation, although it seems that definitive
      MIC values determined by flow cytometry were only possible at 12-h
      postincubation. However, the results obtained by the traditional method were only
      obtained at 24 h, when a visible change in the medium had occurred. At 24 h, both
      methods gave the same result for six antibacterial agents (enrofloxacin,
      ciprofloxacin, gentamicin, streptomycin, chloramphenicol, and oxytetracycline);
      whereas flow cytometry gave slightly higher MIC for tylosin. This was attributed
      to the fact that the M. agalactiae growth that had occurred in the tubes
      containing tylosin was not enough to visibly change the color of the medium.
      Futhermore, flow cytometry detected that inhibitory concentrations of
      oxytetracycline, chloramphenicol, and tylosin as judged at 24 h were not able to
      inhibit the M. agalactiae growth after 48 h. MIC values of enrofloxacin and
      ciprofloxacin were sufficient only to maintain the total counts per milliliter
      throughout the time matched samples, whereas higher concentrations of theses
      antibacterial agents reduced the total counts per milliliter over the course of
      the experiment. The main advantage of the flow cytometric method is that MIC
      results for M. agalactiae can be obtained in a shorter time than is possible with
      the traditional method. The method presented makes identification of resistant
      populations of M. agalactiae possible and, unlike the traditional method, allows
      the effect of each antibacterial agent to be determined in real-time at the
      single-cell level.

PMID- 16998869
TI  - High-throughput fluorescent screening of transgenic animals: phenotyping and
      haplotyping.
AB  - BACKGROUND: Methods for genotyping transgenic animals currently consist of
      extracting genomic DNA from blood or tissue followed by PCR or Southern blot
      analysis. These methods when used to screen large numbers of animals can be time
      consuming and expensive. Therefore, we developed a novel method that allows high
      throughput screening of phenotypic changes on leukocytes, resulting from the
      transgenic genotype. This technique allows investigators to quickly screen a
      large number of animals without the need to extract DNA from each one. Moreover,
      since blood is collected for the initial screening, putative homozygotes can be
      confirmed by conventional methods using the same blood samples. METHODS: We
      collected blood from wild-type alphagal positive and alphagal knockout mice and
      probed for the presence of Galalpha(1-->3)Gal (alphagal) epitopes. Also,
      alloantigen specific antibodies were used to determine the haplotype of our
      outbred mouse colony in order to develop an inbred line. RESULTS: alphagal
      epitopes were detected in wild-type but not alphagal knock-out samples. To
      validate these results, PCR was used to demonstrate the native alphagal gene in
      wild-type and the pGKneo construct in alphagal knock-out mice. Furthermore,
      haplotypes were determined and mice divided for backcrosses. CONCLUSIONS: This
      screening method is useful for both preliminary screening of transgenic mice and
      the development of an inbred mouse colony by rapid determination of MHC I
      haplotype. Here, we demonstrate the use of this technique and show how it can be
      a valuable tool, saving time and resources in both investigator effort and animal
      husbandry.

PMID- 16998870
TI  - Dynamic quantification of the tyrosine phosphorylation of the sperm surface
      proteins during capacitation.
AB  - BACKGROUND: Spermatozoa acquire active fertilizing competence only after
      deposition in the female tract and subsequent capacitation. Recent studies on the
      cellular location of major sperm phosphoproteins suggest that capacitation is
      associated with tyrosine phosphorylation of proteins exposed on the sperm
      surface. However, these changes have not yet been quantified objectively. A
      calcium influx seems to be required for the completion of tyrosine
      phosphorylation in some species; however, the exact temporal coordination between
      these processes is still poorly understood. METHODS: Flow cytometry was used to
      quantify the degree of phosphorylation of the sperm surface proteins by probing
      with fluorescein isothiocyanate-conjugated anti-phosphotyrosine (pY) antibody
      raised in mouse. Dynamic changes in other sperm parameters (calcium influx,
      membrane integrity, and spontaneous acrosome reaction) were assessed to analyze
      their temporal coordination. RESULTS: : The changes in specific phosphotyrosine
      (pY) fluorescence signal detected in live, nonpermeabilized boar cell suspensions
      were biphasic during incubation under capacitating conditions. After 120 min of
      incubation, the degree of pY fluorescence increased threefold, indicating the
      changes in proteins exposed on sperm surface. At the same time there was a
      gradual increase in cytosolic calcium ion levels with the maximal rate at 60 min
      of incubation. This rate slowed immediately before the onset of the massive rise
      in tyrosine phosphorylation and decreased by 90% after its completion. The
      integrity of plasma and acrosome membranes decreased only slowly, illustrating
      that the changes observed were not due to the process of spontaneous acrosome
      reaction. CONCLUSIONS: These data provide quantitative evidence for the
      appearance of tyrosine-phosphorylated proteins on the surface of live boar
      spermatozoa during capacitation. An exact temporal coordination exists between
      cytosolic calcium ion content and protein tyrosine phosphorylation under these
      conditions. This novel approach has the advantage of making possible a precise
      quantification and kinetic comparison of molecular processes in different cell
      subpopulations.

PMID- 16998871
TI  - Chip-on-beads: flow-cytometric evaluation of chromatin immunoprecipitation.
AB  - BACKGROUND: Chromatin immunoprecipitation (ChIP) is a widely used technique for
      the detection of in vivo DNA-protein interactions underlying epigenetic
      regulation. The standard readout of ChIP is based on semi-quantitative or
      quantitative PCR measurements; however, the development of alternative platforms
      with high throughput potentialities is expected to facilitate the introduction of
      this method into routine diagnostics. METHODS: We have established a flow
      cytometry-based alternative for the evaluation of ChIP data. The method is based
      on the capture of the products of a conventional PCR run to low cycle numbers, on
      microbeads. RESULTS: In vivo histone H4 acetylation and H3 lysine 4 methylation
      was detected at the promoter of the tissue transglutaminase type 2 gene. These
      results were confirmed by QPCR measurements. The levels of modifications
      decreased significantly upon apoptosis and were accompanied by the down
      regulation of TGM2 mRNA expression. CONCLUSIONS: This method that we named ChIP
      on-beads, a combination of flow cytometry and conventional PCR, is a reliable and
      efficient alternative in the quantitative analysis of ChIP results, especially
      promising when high throughput monitoring of epigenetic markers of diagnostic
      importance is required. The method is simple enough to be easily implemented in a
      routine flow-cytometric laboratory.

PMID- 16998872
TI  - Reactions of sulfenic acid with 2-mercaptoethanol: a mechanism for the inhibition
      of gastric (H+-K+)-adenosine triphosphate by omeprazole.
AB  - The reactions of omeprazole, a potent proton pump inhibitor (PPI) were
      investigated in the presence of 2-mercapotoethanol. Reactions were monitored in
      solutions buffered to pH values ranging 2.0-8.0 using differential pulse
      polarography (DPP) at the static mercury drop electrode (SMDE). The fast,
      sensitive and selective electrochemical technique facilitated successive
      recordings of voltammograms (peak current (nA) vs. peak potential (volts vs.
      Ag/AgCl)) for all analytes in situe, including the 2-mercaptoethanol. In acidic
      solutions and in the presence of 2-mercaptoethanol, omeprazole undergoes
      degradation into three compounds, the first is a cyclic sulfenamide (D+),
      previously believed to be the active inhibitor of the H+, K+-ATPase, the second
      is the omeprazole dimer, and the third is the disulfide believed to be the
      product of reaction between 2-mercaptoethanol and D+. The cyclic sulfenamide (D+)
      solution was found to be stable in solutions containing 2-mercaptoethanol having
      pH values: 2.0, 4.0, and 6.0. This finding proved conclusively that the cyclic
      sulfenamide is not reactive toward the 2-mercaptoethanol. In contrast to previous
      reports, the conversion of the sulfenic acid intermediate into D+ was found to be
      irreversible. Due to this irreversibility, D+ and sulfenic acid were not rapidly
      interconvertable. The present work suggests that the active inhibitor is the
      sulfenic acid.

PMID- 16998873
TI  - Antibody structure, instability, and formulation.
AB  - The number of therapeutic monoclonal antibody in development has increased
      tremendously over the last several years and this trend continues. At present
      there are more than 23 approved antibodies on the US market and an estimated 200
      or more are in development. Although antibodies share certain structural
      similarities, development of commercially viable antibody pharmaceuticals has not
      been straightforward because of their unique and somewhat unpredictable solution
      behavior. This article reviews the structure and function of antibodies and the
      mechanisms of physical and chemical instabilities. Various aspects of formulation
      development have been examined to identify the critical attributes for the
      stabilization of antibodies.

PMID- 16998874
TI  - A rapid, three-step process for the preformulation of a recombinant ricin toxin A
      chain vaccine.
AB  - A systematic, three-step approach was employed to develop a stable, optimized
      formulation of ricin toxin A-chain V76M/Y80A (rRTA) for use as a vaccine against
      ricin toxicity. The method first uses spectroscopic techniques to evaluate the
      stability of rRTA as a function of temperature and pH. To synthesize the data,
      empirical phase diagrams are generated to display the conditions under which the
      protein maintains particular conformational states. Following identification of
      optimal pH conditions, light scattering and fluorescence assays are employed to
      screen a wide variety of compounds for their abilities to stabilize rRTA. Once
      stabilizers were identified, the ability of rRTA to adsorb to aluminum salt
      adjuvants was evaluated. Desorption of the protein from the adjuvant was also
      analyzed. Using this approach, the optimal formulation conditions for rRTA were
      determined to be pH 6.0 utilizing glycerol as a stabilizer and Alhydrogel as an
      adjuvant. Such an approach has the potential to significantly reduce the time it
      takes to get vaccines into clinical testing.

PMID- 16998875
TI  - Characterisation of norovirus strains in rural Ghanaian children with acute
      diarrhoea.
AB  - The incidence of calicivirus infection in Ghana and many other African countries
      is not known. Thirteen (15.9%) of the 82 diarrhoeic stool samples tested for
      caliciviruses were positive for noroviruses (NoVs). NoVs were present in all age
      groups and were detected only during the diarrhoea peak that coincided with the
      peak rotavirus season. Ten (76.9%) of the NoV detected were genogroup II (GII)
      NoVs and the remaining three (23.1%) genogroup I (GI) NoVs. The predominant GII
      detected was GII-4 (60%, 6/10). Three of the GII NoVs were determined to be
      recombinants of GII-8/GII-14 as deduced from the sequencing of the region
      spanning the Orf1/2 junction. The GII genotypes formed four clusters with
      published GII sequences. The data shown enhances understanding of NoV diversity
      in Ghanaian children and demonstrate the global spread of distinct common
      genotypes to African countries.

PMID- 16998876
TI  - Loss of functional transforming growth factor (TGF)-beta type II receptor results
      in insensitivity to TGF-beta1-mediated apoptosis and Epstein-Barr virus
      reactivation.
AB  - Transforming growth factor (TGF)-beta1 induces not only cell growth inhibition or
      apoptosis but also Epstein-Barr virus (EBV) reactivation in some Burkitt's
      lymphoma (BL) cell lines. The purpose of this study was to define the role of TGF
      beta signaling molecules in response to TGF-beta1-mediated cell growth
      inhibition, apoptosis, and EBV reactivation in BL cell lines. First, we confirmed
      the effect of TGF-beta1 on the cell growth and EBV reactivation in six BL cell
      lines. TGF-beta1 induced cell growth inhibition and EBV reactivation in these
      cell lines but did not in Akata cells. To elucidate the mechanism of TGF-beta1
      unresponsiveness in Akata cells, we studied the expression of TGF-beta receptors
      and the intracellular signaling molecules Smads. All cell lines expressed TGF
      beta type I receptor, Smad2, Smad3, and Smad4. TGF-beta type II receptor (R-II)
      was expressed in all cell lines except Akata cells. Introduction of the TGF-beta
      R-II into Akata cells results in sensitivity to TGF-beta1-mediated growth
      inhibition, apoptosis, and EBV reactivation. In addition, to test a possibility
      to the transcriptional repression of the TGF-beta R-II gene in Akata cells, the
      effect of histone deacetylation (HDAC) inhibitor, trichostatin A (TSA) was
      examined. The expression of TGF-beta R-II in Akata cells was induced by TSA
      treatment. These results suggest that the lack of functional TGF-beta R-II
      impedes the progression of signals through TGF-beta1 and becomes a determinant of
      unresponsiveness to TGF-beta1-mediated growth inhibition and EBV reactivation.

PMID- 16998877
TI  - Thrombophlebitis and upper respiratory tract virus infection.
AB  - During an episode of thrombophlebitis, the 72-year-old correspondent came down
      with a common cold presumably, but not provenly, due to infection by one of the
      rhinoviruses. During the 96 hr period of coryza, all symptoms of thrombophlebitis
      vanished completely. There is experimental evidence that rhinovirus infections
      elicit cytokine production [Stockl et al. (1999): J Clin Invest 104: 957-965],
      and that IL-10 can assuage thrombosis in rats [Downing et al. (1998): J Immunol
      161: 1471-1476].

PMID- 16998878
TI  - Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART
      and HAART treated patients in Burkina Faso.
AB  - Non-B HIV subtypes have been estimated to account for 88% of HIV infections in
      the world. These subtypes are particularly relevant in view of the availability
      of antiretroviral (ARV) drugs, since subtype-specific mutations are associated
      with drug-resistance in developing countries. Therefore, the pol gene sequences
      in HIV-1 isolates were examined from the three distinct groups of 39 infected
      patients from Ouagadougou in Burkina Faso: 17 patients who had not received any
      antiretroviral therapy (ART); 16 patients received ART, and 6 HIV-infected
      children, from infected mothers, received a single Nevirapine dose prophylaxis
      during birth. HIV-1 pol sequencing was successful for 29 samples. As expected,
      all patients presented the common (non-B subtype) M36I polymorphism and 26/29
      (90%) the K20I mutation. Phylogenetic studies showed high predominance of
      recombinant HIV-1 strains: CRF06_cpx 16/29 (55.17%), CRF02_AG 9/29 (31.03%), A1
      2/29 (6.89%), G 1/29 (3.44%), and CRF09_cpx 1/29 (3.44%). Two twins showed, 6
      months after birth, a NNRTI-mutation (Y181C/Y). During the same period, the twin
      mother presented a different NNRTI-mutation (V106I), thus suggesting that the
      different blood drug concentration may determine a different drug-resistance
      pathway. Among 17 non-highly active antiretroviral therapy (HAART) patients, 3/17
      (17.64%) presented virus with reverse transcriptase (RT) mutations [V118I: 1/17
      patients (5.88%), V179E: 2/17 patients (11.76%)]. 10/17 (58.82%) presented virus
      with minor protease (PR) mutations [L63P: 5/17 patients (29.41%), V77I: 3/17
      patients (17.64%), L10I: 2/17 patients (11.76%)]. 4/17 patients did not show any
      PR and RT mutations (23.52%). Among six HAART-treated patients, 6/6 and 3/6 had
      M36I and L63LP protease minor subtypes, respectively; and only two (33.33%)
      presented virus with K103N mutation. The low prevalence of drug-resistant
      associated mutations in Burkina Faso is encouraging. However, further studies
      with a larger cohort with a high non-B subtype prevalence are necessary to
      optimize ART in developing countries.

PMID- 16998879
TI  - Peripheral insulin resistance during treatment of chronic hepatitis C with
      peguilated interferon plus ribavirin.
AB  - Patients with hepatitis C virus (HCV) infection present higher risk of developing
      type-2 diabetes mellitus (DM). However, the mechanism of this association and the
      role of antiviral treatment are still unclear. The objective of this study was to
      investigate the relationship between the use of peguilated interferon and the
      development of insulin resistance (IR) in these patients. METHODS: HOMA index was
      evaluated in 30 HCV-infected patients just before and during the first 6 months
      of treatment with peguilated interferon plus ribavirin. Anthropometrical
      parameters and glucose/cholesterol profile were also monitored. RESULTS: No
      changes in HOMA after 6 months of treatment were observed. Glucose levels
      decreased but not significantly (P = 0.059). Patients with higher HOMA index
      after 6 months of treatment also presented higher aminotransferase levels (P =
      0.03), higher fat index on computed tomography (P = 0.011), longer time of
      exposure to the virus (P = 0.021), and a positive smoking history when compared
      to non-insulin resistant patients (P = 0.045). There was no influence of fibrosis
      stage on liver biopsy in the insulin-resistance development. CONCLUSIONS: No
      changes in the IR were observed after 6 months of treatment. Insulin resistance
      is related to the abdominal fat and anthropometrical parameters rather than to
      the antiviral treatment.

PMID- 16998880
TI  - A chemiluminescent, magnetic particle-based immunoassay for the detection of
      hepatitis C virus core antigen in human serum or plasma.
AB  - Hepatitis C virus (HCV) exposure in blood donors is determined serologically by
      the detection of anti-HCV antibodies in serum or plasma. However, a "window"
      period of 30-70 days after exposure exists where specific antibodies to HCV
      antigens are not detected. The use of nucleic acid testing for the detection of
      HCV RNA or antigen testing for the detection of HCV core protein have resulted in
      dramatic reductions in the pre-seroconversion window period. In this study, an
      automated HCV core antigen detection test was developed. This magnetic
      microparticle-based assay utilizes anti-HCV core monoclonal antibody to capture
      antigen present in human serum or plasma. Captured antigen is then detected using
      an anti-HCV core monoclonal antibody conjugated with a chemiluminescent compound.
      The specificity of this assay was established at 99% upon testing a population of
      normal volunteer blood donors. Sensitivity was determined by testing 16
      commercially available HCV seroconversion panels representing genotypes 1a, 1b,
      2b, and 3a. In each panel tested, HCV core antigen was detected prior to anti-HCV
      antibody, resulting in a reduction of the window period by greater than 23 days
      on average, and greater than 34 days on panels initially NAT negative. In
      addition, HCV core antigen was detected in >97% of HCV RNA positive/antibody
      negative specimens, exhibiting sensitivity nearly equivalent to nucleic acid
      testing in the pre-seroconversion window period for the panels examined.

PMID- 16998881
TI  - Increased frequencies of CD8+ T lymphocytes recognizing wild-type p53-derived
      epitopes in peripheral blood correlate with presence of epitope loss tumor
      variants in patients with hepatocellular carcinoma.
AB  - Wild-type (WT) sequence p53 peptides are attractive candidates for broadly
      applicable cancer vaccines. The aim of this study was to evaluate the potential
      of a WT p53-based immunotherapeutic approach for patients with hepatocellular
      carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT
      p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the
      peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients.
      Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation
      was assessed by analysis of granzyme B and interferon-gamma mRNA transcription,
      using a quantitative real-time polymerase chain reaction assay. Tumor
      immunophenotyping was performed to evaluate the p53 status, the expression of
      major histocompatibility complex (MHC) and costimulatory molecules in freshly
      isolated tumor cells. HCC patients exhibited significantly higher frequencies of
      WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity,
      when compared with healthy controls. Increased frequencies of p53-specific CD8+ T
      cells and their activity correlated with selective HLA-A2 allele loss and reduced
      costimulatory molecule expression of tumor cells. Moreover, augmented numbers of
      p53-specific T cells coincided with high MHC class II expression in tumor cells
      but were inversely related to the T status of the tumor node metastasis staging
      system. Our results indicate the existence of natural immunosurveillance and
      tumor immune evasion, involving a T cell response against WT p53 tumor antigen in
      patients with HCC. These findings may have important implications for the future
      development of cancer vaccines.

PMID- 16998883
TI  - High and persistent excretion of hepatitis A virus in immunocompetent patients.
AB  - The duration and level of virus excretion in blood and faeces of patients with
      hepatitis A virus (HAV) infection were studied in relation to levels of alanine
      aminotransferase (ALT), disease severity and HAV genotype. Clinical data, blood
      and faeces were collected from 27 patients with acute hepatitis A (median age: 33
      years) for a maximum of 26 weeks. Single blood donations from 55 other patients
      with acute HAV (median age: 32 years) were also used. Virus loads were quantified
      by competitive nested RT-PCR. HAV was excreted in faeces for a median period of
      81 days after disease onset, with 50% of patients still excreting high levels at
      Day 36 (2 x 10(6) - 2 x 10(8) copies/ml faeces suspension). Viraemia was
      detected, but not quantifiable, for a median period of 42 days. In the first 10
      days of illness, higher ALT levels were correlated with higher viraemia levels.
      Comparison of patients infected with genotype 1a with those infected with type 1b
      did not differ significantly in terms of the duration of HAV excretion or
      jaundice. In conclusion, faecal excretion of HAV is at a high titre in the first
      month, perhaps making patients infectious for a longer period than assumed
      currently. Blood banks should be aware that viraemia may be present for more than
      1 month, and genotype did not affect the duration of virus excretion or jaundice.

PMID- 16998884
TI  - High prevalence of hepatitis C virus subtypes 4c and 4d in Malaga (Spain):
      phylogenetic and epidemiological analyses.
AB  - Hepatitis C virus (HCV) is a major aetiological agent of chronic hepatitis and it
      may lead to the development of liver cirrhosis and hepatocellular carcinoma. HCV
      has been classified into six clades as a result of high genetic variability. A
      commercial procedure to genotype HCV in 678 patients from Carlos Haya Regional
      University Hospital, Malaga was used to study the distribution of HCV genotypes
      in Malaga, southern Spain. A high prevalence of HCV-4 (10.2%) was found. This
      genotype is found more commonly in Egypt, Central Africa and the Middle East. The
      distribution of the different subtypes in the 69 patients with HCV-4 was as
      follows: 4.3% subtype 4e, 7.2% subtype 4a, 11.5% not subtypable, and 76.8%
      subtype 4c/4d. Of the 53 4c/4d patients, 69% were intravenous drug users and 31%
      non-intravenous drug users. In order to characterise further the HCV-4c/4d
      patients, sequences of the non-structural 5B gene (393 bp) were obtained from 36
      HCV-4c/4d-infected untreated patients. Phylogenetic tree topologies distinguished
      clearly the two subtypes: 11 patients were infected by subtype 4c and 25 by 4d.
      This phylogenetic analysis, reinforced by the epidemiological characteristics,
      suggests the extension of the HCV-4c and -4d subtypes in the area of Malaga among
      both intravenous drug users and non-intravenous drug users.

PMID- 16998885
TI  - Concurrent detection of human herpesvirus type 6 and measles-specific IgMs during
      acute exanthematic human parvovirus B19 infection.
AB  - A familial outbreak of human parvovirus B19 infection is described in which
      serological tests carried out routinely for determining the causal agent of
      febrile rashes of viral etiology failed to yield a definitive diagnosis.
      Concurrent detection of serum IgMs to parvovirus B19 and to heterologous viruses
      such as human herpesvirus type 6 (HHV-6) and measles virus complicated
      interpretation of the data. IgG avidity tests and investigation and testing for
      the presence of viral DNA in sera by PCR were required to confirm parvovirus B19.
      The study stresses the importance of avidity and PCR tests to obtain a firm
      diagnosis of febrile exanthematic viral diseases.

PMID- 16998886
TI  - Rapid diversification of measles virus genotypes circulating in Morocco during
      2004-2005 epidemics.
AB  - Measles virus strains circulating in six different regions in Morocco during 2004
      2005 were analysed. They were genotyped using two different methods: the recently
      developed method based on real-time PCR amplification and melting curve analyses,
      and the conventional method based on nucleic acid sequencing and phylogenetic
      analysis of 456 nucleotides of the 3'-region of the nucleoprotein (N) gene
      sequence. Five genotypes (A, B3.2, C2, D7 and D8) were shown to be circulating
      during this period. Previous studies on measles virus genotypes in Morocco (1998
      2003) showed that only the genotype C2 was present and was considered to be
      endemic. Sequence comparison of the 2004-2005 viruses with other measles strains
      suggests that measles strains belonging to genotype B3.2 were probably imported
      from West Africa, whereas those belonging to genotypes D7 and D8 were imported
      from Europe. These studies which identify the route of importation of measles are
      important for developing strategies for measles elimination in Morocco.

PMID- 16998887
TI  - Serum antibody decay in adults following natural respiratory syncytial virus
      infection.
AB  - Serum antibody decay following RSV infection in adults was examined to evaluate
      the durability of the immune response. Twenty subjects with RSV infection and 10
      subjects who remained RSV uninfected had blood samples obtained over 16-25 months
      analyzed by microneutralization assay and enzyme immunoassay. The mean titers of
      infected subjects rose approximately eightfold post-infection. The mean rate of
      antibody decline was -0.20 log 2 titer per month which led to a > or =fourfold
      drop in titer in 75% of subjects at 1 year. In contrast, titers of uninfected
      subjects were relatively stable. The partial immunity resulting from a boost in
      serum antibody following natural RSV infection in adults appears to be short
      lived.

PMID- 16998888
TI  - SARS-CoV nucleocapsid protein binds to hUbc9, a ubiquitin conjugating enzyme of
      the sumoylation system.
AB  - SARS-CoV is a newly identified coronavirus (CoV) that causes severe acute
      respiratory syndrome (SARS). The SARS-CoV nucleocapsid (N) protein is an
      important structural and functional protein. To identify cellular proteins that
      interact with the SARS-CoV N protein and to elucidate the possible involvement of
      N protein in SARS-CoV pathogenesis, a human lymphocyte cDNA library was screened
      using a yeast two-hybrid system assay. hUbc9, a ubiquitin conjugating enzyme of
      sumoylation system, was found to interact specifically with the N protein,
      implying the post-translational sumoylation of the N protein. Mapping studies
      localized the critical N sequences for this interaction to amino acids 170-210,
      which includes the SR-rich motif. However, the consensus motif of sumoylation
      GK(62)EE in the N protein is not responsible for binding to hUbc9. Mutations of
      hUbc9 at the enzyme active site C93A or C93S severely impair the interaction with
      the N protein. The two proteins were also shown to colocalize in the cytoplasm of
      the transfected 293T cells. This is the first report demonstrating the
      interaction of hUbc9 with a structural protein of plus-strand RNA viruses,
      indicating a new drug target for SARS-CoV.

PMID- 16998889
TI  - Co-circulation of genotype IA and new variant IB hepatitis A virus in outbreaks
      of acute hepatitis in Hungary--2003/2004.
AB  - Hepatitis A virus (HAV) is one of the most important causes of acute infectious
      hepatitis worldwide. In Hungary, the reported number of HAV infections has been
      decreasing in the last four decades, nevertheless, still, each year 500-800 new
      cases and multiple outbreaks occur, particularly in the northeast region of
      Hungary. In Hungary, serology is used routinely to establish the diagnosis of HAV
      infection without genetic analysis of HAV strains for molecular epidemiology. In
      this study, serum samples collected from symptomatic patients were tested by
      enzyme-immunoassay (anti-HAV-IgM ELISA) to establish the cause of three acute
      hepatitis A outbreaks (outbreak 1--from low prevalence region in Southwest
      Hungary in 2003 and outbreaks 2 and 3 from the endemic region in Northeast
      Hungary in 2004). Outbreak strains were characterized by reverse transcription
      polymerase chain reaction (RT-PCR) amplification of a 360 bp viral VP1/2A region,
      amplicon sequencing and phylogenetic analysis. Four, seven, and three sera from
      outbreaks 1, 2, and 3, respectively, were investigated by RT-PCR for HAV genome
      and HAV RNA was detected in 4 (100%), 4 (57%), and 2 (67%) samples. All strains
      belonged to genotype I HAV. Outbreak 1 was caused by the new variant subtype IB
      and outbreaks 2 and 3 caused by genetically identical subtype IA strains. The
      Hungarian IA and IB hepatitis A viruses had the highest nucleotide identity,
      98.4% and 99.0%, to IT-SCH-00 and IT-MAR-02 strains, respectively, detected in
      year 2000 and 2002 in Italy. Endemic subtype IA and probably imported new variant
      subtype IB HAV viruses was detected in outbreaks of hepatitis in Hungary that are
      closely related genetically to HAV strains in Italy.

PMID- 16998890
TI  - A natural inter-genotypic (2b/1b) recombinant of hepatitis C virus in the
      Philippines.
AB  - The prevalence study and the characterization of hepatitis C virus (HCV) was
      carried out in the Philippines and the sequence determination of the 5'
      untranslated region (5'-UTR)-Core and the NS5B regions of HCV was carried out in
      this study. An HCV strain (SE-03-07-1689) collected in Metro Manila, Philippines,
      belonged to discordant subtypes, 2b and 1b in 5'-UTR-Core and NS5B regions,
      respectively. The 9.3 kb sequence of this strain including the entire open
      reading frame was compared with those of the reference strains retrieved from the
      HCV sequences database (GenBank/EMBL/DDBJ) and indicated a recombination event.
      The computation of the sequence similarity mapped a crossover point within the
      NS3 region. This is the second report on the inter-genotype recombinant of HCV
      and the third when an intra-genotype recombinant is included. This recombinant
      strain, SE-03-07-1689, is designated tentatively as RF3_2b/1b according to the
      suggestions used for the other two HCV recombinants.

PMID- 16998891
TI  - Characterization of thromboxane A2 receptor signaling in developing rat
      oligodendrocytes: nuclear receptor localization and stimulation of myelin basic
      protein expression.
AB  - The present work investigates the role of thromboxane A(2) (TXA(2)) receptors in
      the development of oligodendrocytes (OLGs). The results demonstrate that the
      proteins of the TXA(2) signaling pathway, i.e., cyclooxygenase (COX-1), TXA(2)
      synthase (TS), and TXA(2) receptor (TPR) are expressed in the developing rat
      brain during myelination. Furthermore, culture of OLG progenitor cells (OPCs)
      revealed that the expression levels of these proteins as well as TXA(2) synthesis
      increase during OLG maturation. Separate studies established that activation of
      TPRs by the agonist U46619 increases intracellular calcium in both OPCs and OLGs
      as visualized by digital fluorescence imaging. Immunocytochemical staining
      demonstrated that TPRs are localized in the plasma membrane and perinuclear
      compartments in OPCs. However, during OLG differentiation, TPRs shift their
      localization pattern and also become associated with the nuclear compartment.
      This shift to nuclear localization was confirmed by biochemical analysis in
      cultured cells and by immunocytochemical analysis in developing rat brain.
      Finally, it was found that U46619 activation of TPRs in maturing OLGs resulted in
      enhanced myelin basic protein (MBP) expression. Alternatively, inhibition of
      endogenous TPR signaling led to reduced MBP expression. Furthermore, TPR-mediated
      MBP expression was found to be associated with increased transcription from the
      MBP promoter using a MBP-luciferase reporter. Collectively, these findings
      suggest a novel TPR signaling pathway in OLGs and a potential role for this
      signaling during OLG maturation and myelin production.

PMID- 16998892
TI  - Kaposi's sarcoma, human herpesvirus 8 infection and the potential role of
      promoter-arthropod bites in northern Sweden.

PMID- 16998893
TI  - Correlation of norovirus variants with epidemics of acute viral gastroenteritis
      in Hong Kong.
AB  - Norovirus (NV) (formerly called Norwalk-like virus) is the most common
      etiological agent of acute viral gastroenteritis outbreaks worldwide. Recent
      reports have shown that two new GII.4 variants caused epidemics in Europe. To
      investigate if it is also the case in Hong Kong, a molecular epidemiological
      study was undertaken between January 2002 and June 2005. During this period,
      there was a substantial increase in acute cases of gastroenteritis caused by NV.
      Phylogenetic analysis showed that GII.2 and GII.4 are the major circulating
      genotypes. Two new GII.4 variants (variants C and D) were identified in 2002 and
      2004, which quickly became the predominant strains. They were almost identical to
      the variants causing epidemics in Europe recently. Since geographically distinct
      areas were involved within a short period of time, it is possible that GII.4 has
      a particular propensity for causing pandemics.

PMID- 16998894
TI  - Comparison of multiplex PCR assays and conventional techniques for the diagnostic
      of respiratory virus infections in children admitted to hospital with an acute
      respiratory illness.
AB  - The performances of four multiplex PCR (m-PCR) were compared to direct
      immunofluorescence assay (DFA) and HuH7 cell culture for the detection of viruses
      in 263 children admitted to hospital with an acute respiratory illness. One
      hundred fifty (57.6%) nasal aspirates were found DFA-positive; 188 (72.3%) were
      found positive by both DFA and HuH7 cell culture, and 242 (92%) were PCR
      positive. The m-PCR detected 124 viruses which were not found by conventional
      methods: 68 rhinovirus, 17 human metapneumovirus, 15 respiratory syncytial virus
      (RSV), 8 parainfluenza virus (PIV), 5 coronavirus 229E, 3 OC43 and 3 NL63, 4
      enterovirus, 2 influenza virus B and C virus. The m-PCR were more sensitive, had
      the advantages of a shorter delay in specific diagnosis, and a lower cost than
      DFA and culture. Using these m-PCR, the prevalence of each virus was compared
      between in-patient and out-patient groups of children attending the emergency
      unit of the hospital. Nasal aspirates from 411 (91.5%) children were found
      positive by the PCRs. RSV, rhinovirus, and influenza virus were the most frequent
      viruses detected in this population, representing 43.6%, 31.8%, and 8.8% of the
      virus found, respectively, followed by human metapneumovirus (4.4%), coronavirus
      (3.4%), parainfluenza virus (3.2%), adenovirus (2.3%), and enterovirus (2.1%).
      RSVs were detected more significantly in the in-patient group than in the out
      patient group, and influenza viruses were detected more frequently in the out
      patient group than in the in-patient group. Moreover, the use of m-PCR pointed
      out the frequency of rhinovirus and mixed viral detections in these patients. In
      conclusion, according to the requirements of speed and low cost of the methods,
      and to achieve the highest rate of detection of respiratory viruses, the combined
      use of DFA and m-PCR is today likely to be the best way to improve diagnosis of
      respiratory illnesses in children.

PMID- 16998895
TI  - Genetic drift of parvovirus B19 is found in AIDS patients with persistent B19
      infection.
AB  - It is generally thought that parvovirus B19 is stable genetically. Consistently,
      genetic drift has not been found in patients with persistent B19 infection. In
      this report, longitudinal genetic changes in NS1 and VP1 gene of B19 isolates
      from three AIDS patients with persistent B19 infection were studied. One of the
      three patients was not treated with highly active anti-retroviral therapy
      (HAART). B19 viral DNA from these patients was amplified by polymerase chain
      reaction (PCR) and then sequenced directly. A single genetic change was found in
      the B19 isolate obtained from the patient not treated with HAART on Day 10 after
      intravenous immunoglobulin (IVIG) treatment. The nucleotide sequences of B19
      isolated from this patient, then remained unchanged over a period of 11 months.
      Analysis of NS1 clones derived from his longitudinal viral isolates showed the
      existence of quasi-species but genetic drift was not found. One of the other two
      patients treated with HAART experienced treatment failure; he was later treated
      with mega-HAART. In contrast to the genetic stability of B19 isolates from the
      patient not treated with HAART, multiple genetic changes were discovered in the
      viral isolates from the two other patients after HAART and mega-HAART,
      respectively. Through analysis of B19 clones, the frequency of clones containing
      these mutations confirmed the genetic drift. Nucleotide substitutions seen in VP2
      gene of isolates with genetic drift from both patients were all non-conserved,
      suggesting that they are positively selected.

PMID- 16998896
TI  - Characterization of HCV strains in an oncohematological pediatric department
      reveals little horizontal transmission but multiple introductions by un-screened
      blood products in the past.
AB  - Because several children were found infected with hepatitis C virus (HCV) at a
      pediatric oncohematological department in Vilnius, 474 children were tested for
      anti-HCV. Fifty-eight percent of 96 children treated with blood and plasma
      products manufactured before the introduction of anti-HCV screening of blood in
      Lithuania in 1994 were positive for anti-HCV versus 3.4% of those treated after
      1994. The possible route of transmission for 45 of these was investigated by
      phylogenetic analyses within the NS5B region. Children treated before 1995 were
      infected with a multiplicity of strains of different subtypes, predominantly 1b
      found in 21 cases, 3a in 5 cases, 2 in 3 cases, 1a in 1 case, and not subtypeable
      genotype 1 strains in 2 cases. Children who had received blood products after
      1994 were infected with only two subtypes, 1b in six and 3a in seven. Genetic
      analysis showed multiple introductions of HCV before 1995 and that horizontal
      spread between patients had occurred only to a minor extent at the department.
      However, two transmission chains involved children treated before 1995. Another
      chain involved five children treated after 1994. Since the most important risk
      factor for acquiring hepatitis C was blood products manufactured before the
      introduction of donor screening for anti-HCV, the spread between children would
      not have been revealed without molecular tools. These and the background strains
      provide the first reported sequence data on Lithuanian HCV strains. In general,
      these were shown to form autochthonous clades, except the 3a strains that were
      related to strains from the former USSR.

PMID- 16998897
TI  - Detection of HEV antigen as a novel marker for the diagnosis of hepatitis E.
AB  - Infection with hepatitis E virus (HEV) may be diagnosed by the presence of HEV
      RNA or anti-HEV antibodies. An enzyme immunoassay (EIA) was developed for the
      detection of antigen. Twenty-four monoclonal antibodies (mAbs) were produced. An
      indirect sandwich EIA was developed to detect HEV antigen using a combination of
      three mAbs as coating antibodies. Approximately 44.6% (33/74), 28.6% (50/175),
      and none (0/27) of sera positive for anti-HEV IgM alone, both anti-HEV IgM and
      IgG, and anti-HEV IgG alone also were positive for HEV antigen using this EIA.
      Forty-two HEV antibody-positive sera were tested for HEV RNA and antigen in
      parallel and the concordance was 81.0% (34/42). All PCR products were found to
      belong to HEV genotype 4. In order to evaluate the temporal relationship between
      HEV antigen positivity and HEV RNA, anti-HEV IgG and IgM, and ALT concentrations,
      macaques were infected with HEV genotypes 1 and 4 and serial samples were
      collected. The results showed that the antigen EIA can detect the capsid proteins
      of both genotypes. HEV antigen was detectable prior to ALT elevation and the
      appearance of anti-HEV antibodies in the infected monkeys and lasted for several
      weeks in all cases. HEV antigen became detectable in the serum at almost the same
      time as HEV RNA in feces but persisted for 4 weeks less than HEV RNA. This assay
      should be valuable for the diagnosis of acute hepatitis E, particularly in the
      window period prior to seroconversion to anti-HEV.

PMID- 16998898
TI  - Molecular epidemiology of norovirus infections in sporadic cases of viral
      gastroenteritis among children in Northern Italy.
AB  - Surveillance of norovirus infections in sporadic cases of pediatric
      gastroenteritis admitted to a main hospital in Northern Italy during a full-year
      period (2002) showed that noroviruses (10.4%) were the second most common
      causative viral agent, following rotaviruses (21.1%), and noroviruses (81%) were
      mostly implicated in mixed infections. The epidemic period of norovirus was
      September-December, with September and November as months of major prevalence
      (33.3 and 38.5%, respectively). Six distinct norovirus genotypes were detected
      (GI.7, GII.1, GII.2, GII.4, GII.7, GII, not assigned named GIIb), and the
      predominant genotype was GII.4. A "new GII.4 2002 variant" accounted for 82.9% of
      total strains. Since the severity of norovirus symptoms does not usually require
      admission to hospital, the burden of norovirus disease in the general children
      population may be much higher than that suggested by the present hospital-based
      investigation.

PMID- 16998899
TI  - Hesr1 knockout mice exhibit behavioral alterations through the dopaminergic
      nervous system.
AB  - The basic helix-loop-helix (bHLH) transcriptional factor Hesr1 gene (hairy and
      enhancer of split-related 1, also called Hey1/HRT1/CHF2/HERP2) has been
      identified and characterized as a member of the subfamily of hairy/Enhancer of
      split, and shown to be involved in cardiovascular and neural development. We
      report that HESR1 binds directly to a part of the 3' non-coding region of the
      human dopamine transporter (DAT1) gene and represses the endogenous DAT1 gene in
      HEK293 cells. To investigate functions of the HESR1 gene in the dopaminergic
      nervous system in vivo, we analyzed the expressions of dopamine-related genes in
      the postnatal day 0 whole brains of Hesr1 knockout mice by real-time RT-PCR
      analysis. Several dopamine-related genes, such as DAT, dopamine receptors D1, D2,
      D4, and D5, were significantly upregulated. Moreover, young adults of Hesr1
      knockout mice showed a decrease in spontaneous locomotor activity and a reduction
      in exploratory behavior or behavioral responses to novelty in the open-field, and
      elevated plus-maze tests. These results indicate that the HESR1 gene is related
      to neuropsychiatric disorders and behavioral traits through the dopaminergic
      nervous system.

PMID- 16998900
TI  - Positioned to inhibit: netrin-1 and netrin receptor expression after spinal cord
      injury.
AB  - Netrin-1 regulates axon extension during embryonic development and is expressed
      by neurons and myelinating oligodendrocytes in the adult CNS. To investigate the
      potential role of netrin-1 after spinal cord injury, we examined the expression
      of netrin-1 and netrin receptors after sagittal myelotomy in adult rats. This
      lesion targets spinal commissural projections, which respond to netrin-1 during
      development. Netrin-1 mRNA and protein levels were dramatically reduced at the
      site of injury and reduced expression persisted for at least 7 months. Neither
      netrin-1 protein nor mRNA was associated with the glial scar, but netrin-1 was
      expressed by neurons and oligodendrocytes immediately adjacent to the lesion. The
      post-injury distribution detected is similar to that reported for myelin
      associated inhibitors of axon regeneration, such as Nogo, and is distinct from
      the distribution of inhibitors associated with a glial scar. DCC and UNC-5
      homologue (UNC5H) expression also was reduced after injury. Although UNC5H levels
      recovered, DCC expression at the site of injury remained approximately 50% of pre
      injury values at 7 months. Increased UNC5H immunoreactivity was associated with
      fibers in the superficial layers of the dorsal horn and in fibers located in
      white matter adjacent to the lesion. The dominant expression of UNC5H on axons
      and neurons in the spinal cord after injury and the persistent expression of
      netrin-1 by oligodendrocytes surrounding the lesion are consistent with the
      hypothesis that netrin-1 is a myelin-associated inhibitor of axonal regeneration
      after spinal cord injury.

PMID- 16998901
TI  - Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain
      and behavioral deficit in vivo.
AB  - Accumulation of the beta-amyloid peptide (Abeta) in the brain is a major
      pathological hallmark of Alzheimer's disease (AD), leading to synaptic
      dysfunction, neuronal death, and memory impairment. The levels of neprilysin, a
      major Abeta-degrading enzyme, are decreased in AD brains and during aging.
      Because neprilysin cleaves Abeta in vivo, its down-regulation may contribute to
      the pathophysiology of AD. The aim of this study was to assess the consequences
      of neprilysin deficiency on accumulation of murine Abeta in brains and associated
      pathologies in vivo by investigating neprilysin-deficient mice on biochemical,
      morphological, and behavioral levels. Aged neprilysin-deficient mice expressed
      physiological amyloid precursor protein (APP) levels and exhibited elevated brain
      Abeta concentrations and amyloid-like deposits in addition to signs of neuronal
      degeneration in their brains. Behaviorally, neprilysin-deficient mice acquired a
      significantly weaker conditioned taste aversion that extinguished faster than the
      aversion of age-matched controls. Our data establish that, under physiological
      APP expression levels, neprilysin deficiency is associated with increased Abeta
      accumulation in the brain and leads to deposition of amyloid-like structures in
      vivo as well as with signs of AD-like pathology and with behavioral deficits.

PMID- 16998902
TI  - Ectopic expression of phospho-Smad2 in Alzheimer's disease: uncoupling of the
      transforming growth factor-beta pathway?
AB  - Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, has been
      widely suggested to play a role in the pathogenesis of Alzheimer's disease.
      Supporting this, levels of TGF-beta are elevated in the cerebrospinal fluid,
      sera, and brain of patients with Alzheimer's disease. Since TGF-beta is
      neuroprotective, whereas Alzheimer's disease is typified by neurodegeneration, we
      speculated that defects in TGF-beta signaling might abrogate its neuroprotective
      properties. Consistently with an increase in TGF-beta in Alzheimer's disease, we
      found significant increases in phospho-Smad2, a major downstream signaling
      molecule of TGF-beta, in hippocampal neurons of Alzheimer's disease compared with
      age-matched control patients. However, in contrast to an expected nuclear
      localization, phosphorylated Smad2 in Alzheimer's disease was predominantly, and
      ectopically, found in the neuronal cytoplasm, specifically colocalized with
      neurofibrillary tangles and granulovacuolar degeneration. Given that a nuclear
      localization is required to regulate the transcription of TGF-beta target genes
      to afford neuroprotection, the ectopic localization of phosphorylated Smad2
      suggests a defect in the Smad-mediated signaling pathway of TGF-beta in
      Alzheimer's disease and consequent loss of neuroprotective function.

PMID- 16998903
TI  - Astrocytes are more resistant than cerebral endothelial cells toward geno- and
      cytotoxicity mediated by short-term oxidative stress.
AB  - Evidence is accumulating that capillary endothelial cells (cEC) and astrocytes
      play a pivotal role in neuroprotection, in particular with respect to counteract
      oxidative injury. Furthermore, differences among both cell types in response to
      oxidative stress have been shown and astrocytes seem to be more tolerant in terms
      of cytotoxicity, however, no reports exist on oxidative stress mediated
      genotoxicity in astrocytes. We investigated genotoxic and cytotoxic effects of
      oxidative stress in astrocytes and cECs induced by hypoxia/reoxygenation or by
      the redox cycling quinone DMNQ. Additionally, the dependence of these effects on
      glucose availabilty was also studied. On exposure to Hy/Re or 10 muM DMNQ for 24
      hr, the frequency of micronucleated and apoptotic cells was significantly
      increasing, however, astrocytes proved to be more resistant to apoptosis
      induction, in particular on use of DMNQ. In astrocytes, the low background rates
      of necrotic cells were not affected and a significant necrosis induction was only
      detectable in cECs exposed to DMNQ for 24 hr. Short-term exposure to DMNQ (1 hr)
      had no effect in astrocytes but exerted significant geno- and cytotoxicity in
      cECs. Increasing the glucose concentration markedly reduced oxidative stress
      mediated geno- and cytotoxicity in astrocytes. Surprisingly, glucose deprivation
      (aglycemia) suppressed DMNQ induced micronucleus formation in astrocytes without
      affecting the frequency of apoptotic cells. Our results indicate that astrocytes
      are more resistant to oxidative stress than cECs, in particular regarding the
      potential to counteract genotoxicity as well as apoptosis induction mediated by a
      short term oxidative insult.

PMID- 16998904
TI  - Characterization of neuropeptide Y2 receptor protein expression in the mouse
      brain. I. Distribution in cell bodies and nerve terminals.
AB  - Neuropeptide Y (NPY), a 36-amino-acid peptide, mediates biological effects by
      activating Y1, Y2, Y5, and y6 receptors. NPY neurons innervate many brain
      regions, including the hypothalamus, where NPY is involved in regulation of a
      broad range of homeostatic functions. We examined, by immunohistochemistry with
      tyramide signal amplification, the expression of the NPY Y2 receptor (Y2R) in the
      mouse brain with a newly developed rabbit polyclonal antibody. Y2R
      immunoreactivity was specific with its absence in Y2R knockout (KO) mice and in
      adjacent sections following preadsorption with the immunogenic peptide (10(-5)
      M). Y2R-positive processes were located in many brain regions, including the
      olfactory bulb, some cortical areas, septum, basal forebrain, nucleus accumbens,
      amygdala, hippocampus, hypothalamus, substantia nigra compacta, locus coeruleus,
      and solitary tract nucleus. However, colchicine treatment was needed to detect
      Y2R-like immunoreactivity in cell bodies in many, but not all, areas. The densest
      distributions of cell bodies were located in the septum basal forebrain,
      including the bed nucleus, and amygdala, with lower density in the anterior
      olfactory nucleus, nucleus accumbens, caudal striatum, CA1, CA2, and CA3
      hippocampal fields, preoptic nuclei lateral hypothalamus, and A13 DA cells. The
      widespread distribution of Y2R-positive cell bodies and fibers suggests that NPY
      signaling through the Y2R is common in the mouse brain. Localization of the Y2R
      suggests that it is mostly presynaptic, a view supported by its frequent absence
      in cell bodies in the normal mouse and its dramatic increase in cell bodies of
      colchicine-treated mice.

PMID- 16998905
TI  - Chicken suprachiasmatic nuclei: II. Autoradiographic and immunohistochemical
      analysis.
AB  - The vertebrate circadian system is composed of multiple inputs, oscillators,
      pacemakers, and outputs. In birds, the pineal gland and retinae have been defined
      as pacemakers within this system. Evidence for a third, hypothalamic pacemaker is
      abundant. It has been presumed that this pacemaker is homologous to the mammalian
      suprachiasmatic nucleus (SCN). Two candidate structures have been referred to as
      the avian SCN--the medial SCN (mSCN) and the visual SCN (vSCN). Previously, we
      suggested that both structures are involved in a "suprachiasmatic complex." To
      further explore evidence for an avian SCN, the present study employed several
      classical techniques to assess intrinsic characteristics of the mSCN and vSCN in
      the chicken. First, analysis of mSCN and vSCN cytoarchitecture indicated that the
      mSCN is similar in location and cell population to the mammalian SCN, while the
      vSCN is more similar in terms of its shape. Second, intravitreal injections of
      tritiated proline were used to identify hypothalamic retinal terminals. The
      findings support previous studies identifying the vSCN as the primary
      retinorecipient hypothalamic structure in birds. Third, analysis of mSCN and vSCN
      chemoarchitecture suggests that both the mSCN and vSCN display similarity to the
      mammalian SCN, which displays significant interspecies variation. Finally, a
      unique astrocytic bridge between the mSCN and vSCN is demonstrated, suggesting
      that astrocytes play a role within the suprachiasmatic nuclei of birds, similar
      to the situation in mammals. Our previously presented working model of the avian
      suprachiasmatic complex is updated to include these data.

PMID- 16998906
TI  - Synaptic and nonsynaptic localization of GABAA receptors containing the alpha5
      subunit in the rat brain.
AB  - The alpha5 subunit of the GABA(A) receptors (GABA(A)Rs) has a restricted
      expression in the brain. Maximum expression of this subunit occurs in the
      hippocampus, cerebral cortex, and olfactory bulb. Hippocampal pyramidal cells
      show high expression of alpha5 subunit-containing GABA(A)Rs (alpha5-GABA(A)Rs)
      both in culture and in the intact brain. A large pool of alpha5-GABA(A)Rs is
      extrasynaptic and it has been proposed to be involved in the tonic GABAergic
      inhibition of the hippocampus. Nevertheless, there are no studies on the
      localization of the alpha5-GABA(A)Rs at the electron microscope (EM) level. By
      using both immunofluorescence of cultured hippocampal pyramidal cells and EM
      postembedding immunogold of the intact hippocampus we show that, in addition to
      the extrasynaptic pool, there is a pool of alpha5-GABA(A)Rs that concentrates at
      the GABAergic synapses in dendrites of hippocampal pyramidal cells. The results
      suggest that the synaptic alpha5-GABA(A)Rs might play a role in the phasic
      GABAergic inhibition of pyramidal neurons in hippocampus and cerebral cortex.

PMID- 16998907
TI  - Galanin receptor 1 is expressed in a subpopulation of glutamatergic interneurons
      in the dorsal horn of the rat spinal cord.
AB  - The 29/30 amino acid neuropeptide galanin has been implicated in pain processing
      at the spinal level and local dorsal horn neurons expressing the Gal(1) receptor
      may play a critical role. In order to determine the transmitter identity of these
      neurons, we used immunohistochemistry and antibodies against the Gal(1) receptor
      and the three vesicular glutamate transporters (VGLUTs), as well as in situ
      hybridization, to explore a possible glutamatergic phenotype. Gal(1) protein,
      which could not be demonstrated in Gal(1) knockout mice, colocalized with VGLUT2
      protein, but not with glutamate decarboxylase, in many nerve endings in lamina
      II. Moreover, Gal(1) and VGLUT2 transcripts were often found in the same cell
      bodies in laminae I-IV. Gal(1)-protein and galanin-peptide showed an overlapping
      distribution but were not colocalized. Gal(1) staining did not appear to be
      affected by dorsal rhizotomy. Taken together, these findings provide strong
      evidence that Gal(1) is a heteroreceptor expressed on excitatory glutamatergic
      dorsal horn interneurons. Activation of such Gal(1) receptors may thus decrease
      the inhibitory tone in the superficial dorsal horn, and possibly cause
      antinociception.

PMID- 16998909
TI  - Plasticity of synaptopodin and the spine apparatus organelle in the rat fascia
      dentata following entorhinal cortex lesion.
AB  - Synaptopodin is an actin-associated molecule essential for the formation of a
      spine apparatus in telencephalic spines. To study whether synaptopodin and the
      spine apparatus organelle are regulated under conditions of lesion-induced
      plasticity, synaptopodin and the spine apparatus were analyzed in granule cells
      of the rat fascia dentata following entorhinal denervation. Confocal microscopy
      was employed to quantify layer-specific changes in synaptopodin-immunoreactive
      puncta densities. Electron microscopy was used to quantify layer-specific changes
      in spine apparatus organelles. Within the denervated middle and outer molecular
      layers, the layers of deafferentation-induced spine loss, synaptogenesis, and
      spinogenesis, the density of synaptopodin puncta and the number of spine
      apparatuses decreased by 4 days postlesion and slowly recovered in parallel with
      spinogenesis by 180 days postlesion. Within the nondenervated inner molecular
      layer, the zone without deafferentation-induced spine loss, a rapid loss of
      synaptopodin puncta and spine apparatuses was also observed. In this layer, spine
      apparatus densities recovered by 14 days postlesion, in parallel with plastic
      remodeling at the synaptic level and the postlesional recovery of granule cell
      activity. These data demonstrate layer-specific changes in the distribution of
      synaptopodin and the spine apparatus organelle following partial denervation of
      granule cells: in the layer of spine loss, spine apparatus densities follow spine
      densities; in the layer of spine maintenance, however, spine apparatus densities
      appear to be regulated by other signals.

PMID- 16998910
TI  - Reactive astrogliosis induces astrocytic differentiation of adult neural
      stem/progenitor cells in vitro.
AB  - Neural stem cells reside in defined areas of the adult mammalian brain, including
      the dentate gyrus of the hippocampus. Rat neural stem/progenitor cells (NSPCs)
      isolated from this region retain their multipotency in vitro and in vivo after
      grafting into the adult brain. Recent studies have shown that endogenous or
      grafted NSPCs are activated after an injury and migrate toward lesioned areas. In
      these areas, reactive astrocytes are present and secrete numerous molecules and
      growth factors; however, it is not currently known whether reactive astrocytes
      can influence the lineage selection of NSPCs. We investigated whether reactive
      astrocytes could affect the differentiation, proliferation, and survival of adult
      NSPCs by modelling astrogliosis in vitro, using mechanical lesion of primary
      astrocytes. Initially, it was found that conditioned medium from lesioned
      astrocytes induced astrocytic differentiation of NSPCs without affecting neuronal
      or oligodendrocytic differentiation. In addition, NSPCs in coculture with
      lesioned astrocytes also displayed increased astrocytic differentiation and some
      of these NSPC-derived astrocytes participated in glial scar formation in vitro.
      When proliferation and survival of NSPCs were analyzed, no differential effects
      were observed between lesioned and nonlesioned astrocytes. To investigate the
      molecular mechanisms of the astrocyte-inducing activity, the expression of two
      potent inducers of astroglial differentiation, ciliary neurotrophic factor and
      leukemia inhibitory factor, was analyzed by Western blot and shown to be up
      regulated in conditioned medium from lesioned astrocytes. These results
      demonstrate that lesioned astrocytes can induce astroglial differentiation of
      NSPCs and provide a mechanism for astroglial differentiation of these cells
      following brain injury.

PMID- 16998912
TI  - A newly modified 595-nm pulsed dye laser with compression handpiece for the
      treatment of photodamaged skin.
AB  - BACKGROUND AND OBJECTIVES: The pulsed dye laser set the standard of care for the
      treatment of vascular lesions, and recent modifications have enabled improved
      efficacy with fewer side effects. An investigational high energy, variable pulse
      duration pulsed dye laser has been modified to treat both vascular and pigmented
      lesions associated with photoaging. Each laser pulse is comprised of a sequence
      of eight uniform micropulses, which evenly distribute the pulse energy,
      effectively increasing the purpura threshold at any given fluence. Pigmented
      lesions are treated with a compression handpiece (CHP) that removes competing
      vascular target from the field, and helps to prevent purpura. This pilot study
      was undertaken to determine the optimum laser settings, and to investigate the
      ability of this device to improve vascular and pigmented lesions associated with
      photoaging. STUDY DESIGN/MATERIALS AND METHODS: Twenty-four patients with
      photoaged skin and phototype I-III were enrolled in the study. Thirteen received
      treatment for vascular and pigmented lesions, and 11 subjects were treated for
      pigmented lesions alone. Subjects received one to three treatments at 3-4 weeks
      intervals, and underwent 3- and 12-week follow-up evaluation. The degree of
      improvement was assessed by subject evaluation as well as comparison of
      standardized digital photographs by three independent dermatologists. Background
      erythema was treated with a 12-mm spot size, at a fluence of 7 J/cm(2), and a
      pulse width of 10 ms. The cryogen cooling was set at 30 mseconds with a 30 ms
      delay. Individual telangiectasias were treated with a 5- or 7-mm spot size at
      fluences of 9-14 J/cm(2) and pulse widths of 6-20 mseconds. Pigmented lesions
      were treated using a 5- or 7-mm spot size, with energy of 9-15 J/cm(2) and a
      pulse width of 1.5-10 ms without cooling. The CHP had a 7-mm spot size, and
      fluences of 9-16 J/cm(2), and pulse widths of 1.5 or 3 ms were used in the
      treatment of pigmented lesions. RESULTS: The treatment was well tolerated without
      the use of topical anesthetic. All subjects noted improvement in the both
      vascular and pigmented lesions, and were satisfied with their outcomes.
      Objectively, there was moderate improvement in background erythema,
      telangiectasia, and pigmented lesions. Three subjects who were treated with sun
      tans developed transient hypopigmentation and two subjects developed a transient
      textural change following pulse stacking for the treatment of pigmented lesions
      with the conventional handpiece. Purpura was noted in all patients treated for
      pigment with the conventional handpiece at pulsewidths less than 6 mseconds, as
      compared to only one that was treated with the CHP. Three patients treated in
      rapid succession for vascular, and then pigmented lesions with the CHP exhibited
      purpura, which was prevented in future treatments with 1-2 minutes of topical ice
      cooling between passes. CONCLUSIONS: This novel 595-nm pulsed dye laser, with a
      modified pulse sequence and CHP, now has the versatility to safely treat both
      pigment and vascular changes associated with photoaging.

PMID- 16998911
TI  - Structural isoforms of the circadian neuropeptide PDF expressed in the optic
      lobes of the cricket Gryllus bimaculatus: immunocytochemical evidence from
      specific monoclonal antibodies.
AB  - Pigment-dispersing factor (PDF) is an 18-mer peptide that acts as a principal
      neurotransmitter of the insect circadian clock. Our previous study, utilizing
      anti-Uca beta-PDH polyclonal antibody (pAb) to immunolabel the optic lobe of the
      cricket Gryllus bimaculatus, suggested the existence of an alternative PDF-like
      peptide in the outer cells of the first neuropile, or lamina (La), which were
      much less immunoreactive than the inner cells of the second neuropile, the
      medulla (Me). To obtain structural information about such a PDF-like peptide, we
      prepared 10 anti-Gryllus PDF monoclonal (mAb) and pAb antibodies and analyzed
      their detailed epitope specificities. The PDFMe and PDFLa inner cells and their
      axonal projections were clearly immunoreactive to all these antibodies, revealing
      the widespread immunocytochemical organization of the PDF system in the optic
      lobe, as seen previously with anti-Uca beta-PDH pAb and anti-Gryllus PDF mAb, the
      epitope structures of which were also clarified in this study. The lamina outer
      cells, which we found lacked a target pdf mRNA, displayed specific
      immunoreactivities, indicating that the cells contain a distinct PDF-like peptide
      possessing both N- and C-terminal structures. These cells were not immunolabeled
      by some other monoclonal antibodies, however, implying that the PDFLa outer cells
      have a PDF isoform peptide devoid of Asn at positions 6 and 16. This isoform was
      also identified in a varicose arborization in the lamina. These results suggest
      not only the structure of the peptide, but also the possibility of additional
      functions of this novel PDF isoform.

PMID- 16998908
TI  - NTP-CERHR expert panel report on the reproductive and developmental toxicity of
      soy formula.

PMID- 16998913
TI  - Determination of characteristics of degenerative joint disease using optical
      coherence tomography and polarization sensitive optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that optical
      coherence tomography (OCT) could be used to delineate alterations in the
      microstructure of cartilage, and have suggested that changes in the polarization
      state of light as detected by OCT could provide information on the birefringence
      properties of articular cartilage as influenced by disease. In this study we have
      used both OCT and polarization sensitive optical coherence tomography (PS-OCT)
      technologies to evaluate normal and abnormal bovine articular cartilage according
      to established structural, organizational, and birefringent characteristics of
      degenerative joint disease (DJD) in order to determine if this technology can be
      used to differentiate various stages of DJD as a minimally invasive imaging tool.
      MATERIALS AND METHODS: Fresh bovine femoral-tibial joints were obtained from an
      abattoir, and 45 cartilage specimens were harvested from 8 tibial plateaus. Whole
      ex vivo specimens of normal and degenerative articular cartilage were imaged by
      both OCT and PS-OCT, then fixed and processed for histological evaluation. OCT/PS
      OCT images and corresponding histology sections of each specimen were scored
      according to a modified Mankin structural grading scale and compared. RESULTS:
      OCT and PS-OCT imaging allowed structural evaluation of intact articular
      cartilage along a 6 mm surface length to a depth of 2 mm with a transverse
      resolution of 12 microm and an axial resolution of 10 microm. The OCT and PS-OCT
      images demonstrated characteristic alterations in the structure of articular
      cartilage with a high correlation to histological evaluation (kappa = 0.776). The
      OCT images were able to demonstrate early to advanced structural changes of
      articular cartilage while the optical phase retardation images obtained by PS-OCT
      imaging were able to discriminate areas where disorganization of the cartilage
      matrix was present, however, these characteristics are much different than those
      reported where OCT images alone were used to characterize tissue birefringence.
      No evidence of differences in OCT or PS-OCT images were detected between
      specimens of similar structural characteristics where proteoglycan was judged
      present or absent by safranin-O Fast Green staining. CONCLUSIONS: The combined
      use of OCT and PS-OCT technologies to obtain images from a single system is able
      to demonstrate and discriminate between characteristics of very early stages of
      surface irregularities not previously reported for OCT imaging, to deep clefts
      and collagen matrix disorganization for tissue at depths of up to 2 mm with good
      correlation to histology. PS-OCT and accumulated optical phase retardation images
      of articular cartilage as constructed from alterations in Stokes vector
      parameters appear to give a valuable but different assessment of alterations in
      tissue birefringence and organization than have been reported for OCT images
      obtained with the use of polarized or non-polarized light sources. This is the
      first time that alterations in the polarization state of light reflected from
      within the tissue have been demonstrated to be consistent with changes observed
      in the orientation and organization of the collagen matrix in advanced stages of
      DJD. The degree of phase transformation of light reflected from within the tissue
      as determined by PS-OCT imaging does not appear to be altered by the presence or
      absence of proteoglycan.

PMID- 16998914
TI  - Controlling thermal damage of incisions using diamond, copper, and sapphire heat
      conducting templates with and without cooling.
AB  - INTRODUCTION: We investigated the reduction of thermal damage to the surrounding
      tissue when laser incisions were made with and without using thermal conducting
      templates at room temperature and cooled to 5 degrees C. STUDY DESIGN/MATERIALS
      AND METHODS: We used the Vanderbilt free-electron laser (FEL) at 5.4, 6.1, 6.45,
      and 7.7 microns. We also used a conventional continuous wave (CW) carbon dioxide
      laser at 10.6 microns. Incisions were made on 5x10 mm pieces of human breast skin
      (in vitro) and analyzed with histology. Computer morphometrics were used to
      measure the amount of thermal damage. RESULTS: All templates produced a
      statistically significant reduction in the thermal damage. Additionally, we
      showed that cooling the templates made a statistically significant greater
      reduction in the thermal damage. The cooled diamond template reduced the thermal
      damage from the FEL to 28% of the damage observed without a template. The same
      cooled template reduced the thermal damage from the CO(2) laser to 56% of the
      damage observed without a template. Lesser reductions were observed with the
      copper template and even less with the sapphire template. The sapphire template
      reduced the thermal damage to 39 and 67% of the damage observed without a
      template for the FEL and the CO(2) laser, respectively. CONCLUSION: These results
      indicate that unwanted lateral thermal damage from laser incisions can be reduced
      with cooled thermally conductive templates with the best results obtained with
      the diamond template, which is also the best thermal conductor.

PMID- 16998915
TI  - Distinct and gradient distributions of connexin26 and connexin30 in the cochlear
      sensory epithelium of guinea pigs.
AB  - Connexin26 (Cx26) and Cx30 are predominant isoforms of gap junction channels in
      the cochlea and play a critical role in hearing. In this study, the cellular
      distributions of Cx26 and Cx30 in the cochlear sensory epithelium of guinea pigs
      were examined by immunofluorescent staining and confocal microscopy in whole
      mounts of the cochlear sensory epithelium and dissociated cell preparations. The
      expression of Cx26 and Cx30 demonstrated a longitudinal gradient distribution in
      the epithelium and was reduced threefold from the cochlear apex to base. The
      reduction was more pronounced in the Deiters cells and pillar cells than in the
      Hensen cells. Cx26 was expressed in all types of supporting cells, but little
      Cx30 labeling was seen in the Hensen cells. Cx26 expression in the Hensen cells
      was concentrated mainly in the second and third rows, forming a distinct band
      along the sensory epithelium at its outer region. In the dissociated Deiters
      cells and pillar cells, Cx30 showed dense labeling at the cell bodies and
      processes in the reticular lamina. Cx26 labeling largely overlapped that of Cx30
      in these regions. Cx26 and Cx30 were also coexpressed in the gap junctional
      plaques between Claudius cells. Neither Cx26 nor Cx30 labeling was seen in the
      hair cells and spiral ganglion neurons. These observations demonstrate that Cx26
      and Cx30 have a longitudinal gradient distribution and distinct cellular
      expression in the auditory sensory epithelium. This further supports our previous
      reports that Cx26 and Cx30 can solely and concertedly perform different functions
      in the cochlea.

PMID- 16998916
TI  - Heme oxygenase and cyclooxygenase in the central nervous system: a functional
      interplay.
AB  - Heme oxygenase (HO) and cyclooxygenase (COX) are two hemeproteins involved in the
      regulation of several functions in the nervous system. Heme oxygenase is the
      enzyme responsible for the degradation of heme into ferrous iron, carbon monoxide
      (CO), and biliverdin, the latter being further reduced in bilirubin (BR) by
      biliverdin reductase. Heme oxygenase-derived CO is a gaseous neuromodulator and
      plays an important role in the synaptic plasticity, learning and memory
      processes, as well as in the regulation of hypothalamic neuropeptide release,
      whereas BR is an endogenous molecules with antioxidant and anti-nitrosative
      activities. Cyclooxygenase is considered a pro-inflammatory enzyme as free
      radicals and prostaglandins (PGs) are produced during its catalytic cycle.
      Although PGs are also involved in a variety of physiologic conditions including
      angiogenesis, hemostasis, or regulation of kidney function, upregulation of COX
      and increase in PGs levels are a common feature of neuroinflammation. In the
      brain, a functional interplay exists between HO and COX. Heme oxygenase regulates
      COX activity by reducing the intracellular heme content or by generating CO,
      which stimulates PGE(2) release. Increased levels of PGs, free radicals, and the
      associated oxidative stress serve in the brain as a trigger for the induction of
      HO isoforms which increases cellular antioxidant defenses to counteract oxidative
      damage. The importance of the interaction between HO and COX in the regulation of
      physiologic brain functions, and its relevance to neuroprotective or
      neurodegenerative mechanisms are discussed.

PMID- 16998917
TI  - Antiinflammatory but no neuroprotective effects of melatonin under clinical
      treatment conditions in rabbit models of bacterial meningitis.
AB  - Neuronal injury is frequent in bacterial meningitis, resulting in a high rate of
      death and neurological sequelae. In a search of potential neuroprotective
      strategies for treatment of bacterial meningitis, the antioxidant melatonin was
      neuroprotective in cell culture experiments and in a rabbit Streptococcus
      pneumoniae meningitis model, when treatment was started at the time of infection.
      In the present study, adjunctive melatonin treatment applied from the beginning
      of antibiotic therapy 12 hr after infection at a dose of 1.67 mg/kg/hr resulted
      in plasma concentrations of 451 +/- 198 ng/ml, cerebrospinal fluid (CSF)
      concentrations of 154 +/- 57 ng/ml and a CSF-to-plasma ratio of 0.38 +/- 0.19
      (mean +/- SD). Melatonin therapy had antiinflammatory effects but did not reduce
      neuronal injury in either a rabbit model of gram-positive Streptococcus
      pneumoniae or gram-negative Escherichia coli meningitis.

PMID- 16998919
TI  - Effects of stress and corticosterone on activity and plasticity in the amygdala.
AB  - The basolateral amygdala (BLA) has been repeatedly shown to mediate the effects
      of stress on memory-related processes. However, the way in which stress
      influences BLA itself has not been fully explored. We studied the effects of
      stress and corticosterone (CORT) on activity and plasticity in the BLA in the
      rat, using the electrophysiological procedure of long-term potentiation (LTP)
      induction in vivo. Rats were exposed to an acute elevated-platform stress or
      administered vehicle or 5 mg/kg, 10 mg/kg, or 25 mg/kg of CORT systemically,
      after which they were anesthetized and prepared for field potential recording in
      the BLA, in response to stimulation of the entorhinal cortex. The elevated
      platform stress enhanced baseline responses in BLA and plasma CORT but inhibited
      amygdalar LTP. Systemic injections of CORT enhanced baseline responses in BLA in
      a dose-dependent manner but did not influence amygdalar LTP. Posttetanic
      potentiation (PTP) was similarly reduced in CORT- and vehicle-injected groups,
      possibly because of an additional stress from the injection, thus implying that
      PTP and LTP in the amygdala differentially react to stress. These results suggest
      that the increase in amygdalar baseline activity following the exposure to stress
      may be mediated by the concomitant increase in plasma CORT. However, the
      suppression of amygdalar LTP is not a result of elevated levels of CORT,
      suggesting that activity and plasticity in the amygdala might be mediated by
      different mechanisms.

PMID- 16998918
TI  - Intravenous administration of glial cell line-derived neurotrophic factor gene
      modified human mesenchymal stem cells protects against injury in a cerebral
      ischemia model in the adult rat.
AB  - Intravenous administration of human mesenchymal stem cells (hMSCs) prepared from
      adult bone marrow has been reported to ameliorate functional deficits after
      cerebral artery occlusion in rats. Several hypotheses to account for these
      therapeutic effects have been suggested, and current thinking is that
      neuroprotection rather than neurogenesis is responsible. To enhance the
      therapeutic benefits of hMSCs potentially, we transfected hMSCs with the glial
      cell line-derived neurotrophic factor (GDNF) gene using a fiber-mutant F/RGD
      adenovirus vector and investigated whether GDNF gene-modified hMSCs (GDNF-hMSCs)
      could contribute to functional recovery in a rat permanent middle cerebral artery
      occlusion (MCAO) model. We induced MCAO by using intraluminal vascular occlusion,
      and GDNF-hMSCs were intravenously infused into the rats 3 hr later. MRI and
      behavioral analyses revealed that rats receiving GDNF-hMSCs or hMSCs exhibited
      increased recovery from ischemia compared with the control group, but the effect
      was greater in the GDNF-hMSC group. Thus, these results suggest that intravenous
      administration of hMSCs transfected with the GDNF gene using a fiber-mutant
      adenovirus vector may be useful in the cerebral ischemia and may represent a new
      strategy for the treatment of stroke.

PMID- 16998920
TI  - Electrical coupling, receptive fields, and relative rod/cone inputs of horizontal
      cells in the tiger salamander retina.
AB  - Light responses, dendritic/axonal morphology, receptive field diameters, patterns
      of dye coupling, and relative rod/cone inputs of various types of horizontal
      cells (HCs) were studied using intracellular recording and Lucifer
      yellow/neurobiotin dye injection methods in the flatmount tiger salamander
      retina. Three physiologically and morphologically distinct types of HC entities
      were identified. 1) The A-type HCs are somas that do not bear axons, with average
      (+/-SE) soma diameters of 20.01 +/- 0.59 microm, relatively sparse and thick
      dendrites, and they resemble the A-type HC in mammals. The average receptive
      field diameter of these cells is 529.6 +/- 10.87 microm and they receive inputs
      predominantly from cones. 2) The B-type HCs are broad-field somas that bear thin
      and long axons, with average soma diameters of 17.67 +/- 0.38 microm, thinner
      dendrites of higher density, and they resemble the B-type HC in mammals. The
      average receptive field diameter of these cells is 1,633.55 +/- 37.34 microm and
      they receive mixed inputs from rods and cones. 3) The B-type HC axon terminals
      are broad-field, coarse axon terminal processes and they resemble the B-type HC
      axon terminal in rabbits. The average receptive field diameter of these axon
      terminals is 1,291.67 +/- 24.02 microm and they receive mixed inputs from rods
      and cones. All these types of HC are dye-coupled with adjacent HCs of the same
      type. Additionally, B-type HCs and axon terminals are dye-coupled with
      subpopulations of bipolar cells whose axon terminals ramify in the proximal half
      of the inner plexiform layer, raising the possibility that these HCs may send
      feedforward antagonistic surround responses to depolarizing bipolar cells through
      electrical synapses.

PMID- 16998921
TI  - Cerebellar modulation of feeding-related neurons in rat dorsomedial hypothalamic
      nucleus.
AB  - Cerebellum has newly been implicated in many more nonsomatic functions other than
      motor control. Previous studies indicate that the cerebellum is involved in
      feeding regulation and that the gastric vagal nerves transmit short-term meal
      related visceral signals, including cholecystokinin (CCK), into the hypothalamus.
      Recently, the dorsomedial hypothalamic nucleus (DMN) has been thought to play an
      important role in feeding control. Here we investigate whether the inputs from
      cerebellar interpositus nucleus (IN) can reach and converge onto single DMN
      neurons with some feeding-related visceral signals, including gastric vagal
      inputs, CCK, and blood glucose, whose concentration is closely linked to food
      intake. Among the 259 DMN neurons recorded, 120 (46.3%) and 169 (65.3%) responded
      to the cerebellar IN and gastric vagal stimulations, respectively. Within the 120
      DMN neurons responsive to the cerebellar IN stimulation, 98 (81.7%) also
      responded to the gastric vagal stimulus, and a summation of the responses was
      observed further (n = 20), suggesting a convergence and interaction of cerebellar
      and gastric vagal inputs on the cells. Moreover, among the 98 cells receiving
      convergent inputs from cerebellar IN and gastric vagal nerves, 69 (70.4%) were
      identified to be glycemia sensitive, and 22 (68.8%) of the 32 tested neurons were
      also sensitive to systemic CCK. These results demonstrate that the DMN integrates
      somatic information forwarded by the cerebellar IN and visceral signals related
      to food intake, including gastric vagal, CCK and glycemia, and
      electrophysiologically reveal a novel cerebellohypothalamic IN-DMN pathway
      through which the cerebellum may actively participate in short-term feeding
      regulation.

PMID- 16998922
TI  - Staphylococcal alpha-toxin causes increased tracheal epithelial permeability.
AB  - Staphylococcus aureus is an important cause of pulmonary infections. The role of
      S. aureus alpha-toxin as a virulence factor is unclear. We hypothesized that
      airway epithelium is a target of S. aureus alpha-toxin and that exposure of
      airway epithelium to alpha-toxin results in damage to the airway epithelium. To
      examine the hypothesis that alpha-toxin is capable of independently producing
      airway epithelium damage as measured by permeability and morphometry, an isolated
      whole mouse trachea test apparatus was developed. In vitro epithelial
      permeability (P) was calculated and digital micrographs were analyzed
      morphometrically. Purified S. aureus alpha-toxin produced a significant increase
      in tracheal epithelial P (P < 0.05). Morphometric analysis revealed the ratio of
      adherent tracheal epithelium attached to the basement membrane divided by the
      total length of the basement membrane decreased in a dose-dependent manner with 1
      microg/ml alpha-toxin and 10 microg/ml alpha-toxin (P < 0.05). We developed a
      novel isolated whole mouse trachea test apparatus for the measurement of tracheal
      epithelium damage. Increased P and separation of the tracheal epithelium from the
      basement membrane occurred after S. aureus alpha-toxin exposure. We conclude that
      mammalian airway epithelium is a target of S. aureus alpha-toxin.

PMID- 16998923
TI  - Mucoid impaction: an unusual form of allergic bronchopulmonary aspergillosis in a
      patient with cystic fibrosis.
AB  - We reported a child with cystic fibrosis (CF) who developed mucoid impaction
      related to allergic bronchopulmonary aspergillosis (ABPA). This is the first
      reported case of mucoid impaction related to ABPA in CF described to date in the
      literature. The case was successfully treated by corticosteroids and itraconazole
      therapy, but relapsed 6 months later. During exacerbation therapy, cataract
      formation complicated the corticosteroid treatment. We want to emphasize that 6
      months therapy may be inadequate for the treatment of ABPA, and it is important
      to monitor for possible complications of corticosteroids therapy.

PMID- 16998924
TI  - Re: "Circulating levels of KL-6 in acute respiratory distress syndrome sepsis or
      traumatic brain injury in critically ill children" by Briassoulis et al. (Pediatr
      Pulmonol 2006; 41:790-795).

PMID- 16998925
TI  - Inspiratory muscle training in Morquio's syndrome: a case study.
AB  - We reported a case of MPS IV A presented with dyspnea on exertion and respiratory
      muscle weakness. The patient underwent inspiratory muscle training (IMT) using
      threshold loading for 18 weeks. After 6 weeks of initial IMT, aerobic exercise
      training consisting of walking was added to the treatment program. Inspiratory
      muscle strength increased 70%, and 6-minute walk test (6MWT) distance increased
      to 47 m. With the inclusion of aerobic exercise training, additional increases in
      inspiratory muscle strength (7%) and 6MWT distance (26.5 m) were obtained.
      Exertional dyspnea improved from severe to slight after 6 weeks of IMT, and to
      very slight after additional 12 weeks of combined aerobic training and IMT.
      Health-related quality of life improved especially in social function, emotional
      function, vitality, and physical role. In conclusion, inspiratory muscles can be
      trained with the improvement of muscle strength in a patient with Morquio's
      syndrome.

PMID- 16998926
TI  - Lung function measurements in a preterm animal model of respiratory failure:
      comparison of two different neonatal ventilators.
AB  - A variety of ventilators are used in the NICU. Ventilator and lung function
      measures are often applied in weaning protocols or as outcome variables. The
      effect of different ventilators on these measures has not been well studied. Our
      objective was to compare ventilator and lung function measurements in a chronic
      preterm animal model managed with two different neonatal ventilators. Timed
      baboon pregnancies exposed to antenatal steroids were delivered by C/S at 125
      days (term = 185 days). Infants were immediately intubated, given surfactant, and
      ventilated with low tidal volumes (4-6 ml/kg) for 6-14 days using well-defined
      protocols. One group was ventilated via InfantStar (IS) and the other by VIP-Bird
      (VIP). Physiologic and pulmonary function data were serially recorded with the
      VitalTrends plethysmography system. Between ventilator comparisons were made.
      InfantStar (IS) was used on 22 infants in 2002-03, VIP was used on 29 infants in
      2004-05. No differences were found for gestation, birth weight, gender, paO(2),
      paCO(2), FiO(2), arterial/alveolar ratio, dynamic compliance, inspiratory
      resistance, or tidal volumes. From 24 to 336 h, peak and mean airway pressure,
      ventilator rate, and ventilatory efficiency index (VEI: PIP x R x CO(2)/1,000)
      were significantly greater in the VIP group at multiple time points. VIP use was
      associated with a significant increase in expiratory airway resistance (Rexp -
      cmH(2)O/L/s) at all but one-time points studied. Compared to the IS, use of the
      VIP-Bird ventilator in surfactant treated immature baboons with RDS was
      associated with increased expiratory airway resistance and indices of impaired
      ventilation, but not oxygenation. Ventilator management in the NICU, especially
      weaning, may be affected by the specific ventilator in use.

PMID- 16998927
TI  - Use of the laryngeal mask airway in patients with severe muscular dystrophy who
      require sedation or anesthesia.
AB  - Severe muscular dystrophy (MD) has historically led to death in early adulthood,
      due to mainly cardiopulmonary complications. However, with newer methods of
      cardiac and respiratory management, survival has improved, and patients with MD
      are more frequently undergoing procedures requiring deep sedation or anesthesia.
      Respiratory management of these patients during procedures is challenging; safe
      and effective options for respiratory support are needed. In this report, we
      describe our experience using the laryngeal mask airway (LMA) to provide
      respiratory support during deep sedation or anesthesia for eight patients with
      severe MD during the following medical procedures: eight percutaneous endoscopic
      gastrostomy (PEG) placements, three lithotripsies, and placement of an
      implantable cardioverter-defibrillator. We also review the benefits and risks of
      the LMA in the context of other respiratory support options for people with MD,
      and the integral role of non-invasive positive pressure ventilation (NPPV) during
      induction of and recovery from deep sedation or general anesthesia.

PMID- 16998928
TI  - Immunocytochemical analysis of GABA-positive and calretinin-positive horizontal
      cells in the tiger salamander retina.
AB  - By using immunocytochemical techniques, we demonstrate that there are two
      distinct, nonoverlapping populations of horizontal cells (HCs) in the tiger
      salamander retina: GABA-positive cells account for about 72% and GABA-negative
      (calretinin-positive) cells account for 28% of the total HC somas. The calretinin
      positive HCs have relatively sparse and thick dendrites: soma diameter of 19.72
      +/- 0.29 microm, and soma density of 140 +/- 13 cells/mm(2), morphological
      features very much like the A-type HCs described in the accompanying article. The
      GABA-positive HCs have thinner dendritic and coarse axon-terminal-like processes
      of higher density: soma diameter of 18 +/- 0.18 microm, and soma density of 364
      +/- 18 cells/mm(2), features that very much resemble the B-type HCs and B-type HC
      axon terminals in the accompanying article. By using double and triple
      immunostaining techniques we found that only 18% of the non-GABAergic HC
      dendritic clusters contact rods, whereas the remaining 82% of the dendritic
      clusters contact cones. This is consistent with the physiological finding in the
      accompanying article that the A-type HCs are cone-dominated. On the other hand,
      32% of GABAergic HC dendrites contact rod pedicles and 68% contact cone pedicles,
      consistent with the physiological finding that B-type HCs and B-type HC axon
      terminals receive mixed rod/cone inputs. Detailed confocal microscope analysis
      shows that 4% rods, 6% principal double cones/single cones, and 100% accessory
      double cones contact calretinin-positive HCs, and 79% rods, 100% principal double
      cones, 14% accessory double cones, and 82% single cones contact GABAergic HCs.
      These results suggest that GABAergic and non-GABAergic HC input/output synapses
      differ and they may mediate different functional pathways in the outer retina.

PMID- 16998929
TI  - Cerebral oximetry improves detection of sickle cell patients at risk for
      nocturnal cerebral hypoxia.
AB  - We previously used cerebral oximetry to identify low cerebral venous oxygen
      saturation in waking children with sickle cell disease (SCD). Because arterial
      oxyhemoglobin desaturation is common during sleep in SCD patients, this study
      compared both waking and sleeping systemic arterial and cerebral venous
      oxygenation dynamics in children with and without SCD. Seventeen African-American
      (AA) children with homozygous SCD [8 (4-15) years; 29% male; normal transcranial
      Doppler velocities] were compared with a control cohort (CON) comprised of six
      healthy AA children [9 (4-16) years, 33% male]. Standard all-night
      polysomnographic recordings were performed, including measurement of arterial
      oxygen saturation by pulse oximetry (SpO(2)). Regional cerebral oxygen saturation
      (rSO(2)) was measured non-invasively with cerebral oximetry. Intra-cohort
      comparisons examined the influence of sleep on SpO(2) and rSO(2) in the subjects.
      Inter-cohort comparisons of SpO(2), rSO(2,) and the rSO(2)/SpO(2) ratio assessed
      the impact of SCD on systemic and cerebral oxygenation during wakefulness and
      sleep. Cohort differences in SpO(2) were not statistically significant in either
      wakefulness or sleep. However, only in the SCD cohort was the magnitude of SpO(2)
      change statistically significant (P = 0.002). In contrast, both waking and sleep
      rSO(2) cohort median values did differ significantly [awake: CON 76 (67-86) vs.
      SCD 62 (58-71), P = 0.01; sleep: CON 65 (60-77) vs. SCD 55 (48-61), P = 0.01)].
      The waking rSO(2)/SpO(2) ratio was also significantly lower in the SCD group [CON
      0.78 (0.68-0.88) vs. SCD of 0.66 (0.61-0.72); P = 0.015]. During sleep, the ratio
      was also significantly lower in the SCD group [CON 0.71 (0.66-0.81) vs. SCD 0.59
      (0.52-0.65); P = 0.011]. Our findings suggest that SCD patients may be at
      increased risk of cerebral hypoxia during both wakefulness and sleep.

PMID- 16998930
TI  - Passive respiratory mechanics measured during natural sleep in healthy term
      neonates and infants up to 8 weeks of life.
AB  - The single occlusion technique (SOT) is a simple and noninvasive technique for
      measurement of passive respiratory mechanics in infants. Reference values based
      on measurements of a large population of healthy infants performed outside
      specialized research laboratories are lacking. The aim of this study was to
      present reference values for passive respiratory mechanics based on a large
      population of healthy term neonates and infants measured during natural sleep in
      routine care. As part of the ongoing Wheezing Illnesses Study Leidsche Rijn
      (WHISTLER), the compliance (C(rs)) and resistance (R(rs)) of the respiratory
      system were measured in 450 healthy unsedated neonates and infants with a mean
      age of 4.6 +/- 1.3 weeks. Multivariable regression analysis, with gestational
      age, age at measurement, body size, sex, and ethnicity as possible predictors,
      was carried out to estimate prediction equations for mean C(rs) and R(rs) values.
      Technically acceptable lung function measurements could be performed in 328 (73%)
      neonates and infants. Median C(rs) was 39.5 (range 14.8-79.1) ml/kPa and median
      R(rs) was 7.4 (range 3.8-19.5) kPa/L/sec. The following regression equations for
      C(rs) and R(rs) were obtained: ln C(rs) = 1.677 + 1.3 x 10(-4) x birth weight (g)
      + 0.030 x birth length (cm) and ln R(rs) = 2.496-3.1 x 10(-6) x birth length(3)
      (cm(3)) - 0.114 x sex. We provided reference values for passive respiratory
      mechanics using the SOT in a large population of healthy term neonates and
      infants measured during natural sleep. These data provide a frame of reference
      for assessing the normality of SOT measurements performed in routine care.

PMID- 16998931
TI  - Correlation of immunophenotype with progression-free survival in patients with
      gastrointestinal stromal tumors treated with imatinib mesylate.
AB  - BACKGROUND: The therapy for gastrointestinal stromal tumor (GIST) has been
      revolutionized by imatinib mesylate (IM). It is unknown whether the levels of KIT
      expression or the presence of CD34, smooth muscle actin (SMA), desmin, or S-100
      protein predicts patient outcome from IM therapy. In the current study, the
      prognostic effects for KIT and other proteins (CD34, SMA, desmin, S-100) were
      analyzed in a series of GISTs in which protein expression was evaluated by
      immunohistochemical analysis (IHC). METHODS: The cases of 106 patients with GIST
      who were uniformly treated with IM at the study institution between December 15,
      2000, and January 13, 2002 were evaluated retrospectively. The association
      between KIT intensity, CD34, desmin, SMA, S-100 protein, and progression-free
      survival (PFS) was studied. Kaplan-Meier analysis and the Cox proportional
      hazards regression model were used for statistical analysis. RESULTS: The
      majority of tumors arose from the stomach (37%), small intestine (35%), and
      colorectum (14%). KIT expression as determined by IHC was categorized as weak
      (10%), intermediate (32%), or strong (58%). Patient tumors expressed CD34 (75%),
      SMA (56%), desmin (1%), and S-100 protein (32%). Patients whose GIST had weak,
      intermediate, or strong KIT expression were found to have an 18-month PFS rate of
      80%, 84%, and 69%, respectively (P = .30). The presence or absence of CD34, SMA,
      desmin, or S-100 protein did not appear to correlate with PFS after IM.
      CONCLUSIONS: Patients with the appropriate clinical presentation and KIT-positive
      GIST tumors appear to benefit from IM independent of the level of KIT or the
      expression of CD34, SMA, desmin, or S-100 protein by IHC.

PMID- 16998932
TI  - Extrapulmonary small cell cancer: a Canadian province's experience.
AB  - BACKGROUND: The objective of this study was to determine variables that correlate
      with the survival of patients with extrapulmonary small cell carcinoma (EPSCC).
      METHODS: Medical records of 101 eligible patients with EPSCC who were diagnosed
      in Saskatchewan from 1971 to 2002 were reviewed. Survival was calculated by using
      the Kaplan-Meier method. A logistic regression analysis with a backward
      elimination was carried out to determine prognostic variables that predicted
      mortality. RESULTS: The median patient age was 72 years (range, 24-100 years),
      and the male-to-female ratio was 1.4:1. The primary disease sites were as
      follows: breast, 9%; gastrointestinal, 20%; genitourinary, 18%; gynecologic, 11%;
      head and neck, 10%; thymus, 2%; and unknown primary site, 31%. Fifty-one patients
      had limited disease (LD), and 50 patients had extensive disease (ED). Patients
      with LD had a median overall survival of 34 months (range, 0.2-276 months)
      compared with 2 months (range, 0.1-108 months) in patients with ED (P < .0001).
      Among different primary sites, patients with gynecologic small cell cancer (SCC)
      had a median survival of 54.4 months, whereas patients with SCC of an unknown
      primary site had a survival of 2.5 months. Among various variables that were
      examined with respect to their prognostic importance, an abnormal white blood
      cell count (odds ratio [OR], 6.9; 95% confidence interval [95% CI], 3.4-14.1), an
      Eastern Cooperative Oncology Group performance status >2 (OR, 4.5; 95% CI, 2.1
      9.9), and ED (OR, 2.7; 95% CI, 1.4-5.0) were found to be correlated significantly
      with mortality. CONCLUSIONS: The gastrointestinal and genitourinary tracts were
      the 2 major sites involved by EPSCC in the current series. Survival varied
      according to the primary sites, and patients with gynecologic tumors had the best
      prognosis. An abnormal white blood cell count, a poor performance status, and
      disease extent were important factors in predicting survival.

PMID- 16998933
TI  - Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma.
AB  - BACKGROUND: Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm
      that develops in the presence of KS-associated herpesvirus (KSHV) and immune
      perturbation. In the current study, the authors compared CKS cases with age
      matched and sex-matched KSHV-seropositive controls without human immunodeficiency
      virus-1 infection and markers of viral control, blood counts, CD4-positive and
      CD8-positive lymphocytes, and serum beta-2-microglobulin and neopterin levels.
      METHODS: Viral loads were detected using real-time amplification of the KSHV-K6
      and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked
      immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected
      using immunofluorescence. Odds ratios (OR) and 95% confidence intervals (95% CI)
      were calculated using logistic regression adjusted for sex, age, and study site.
      RESULTS: Peripheral blood mononuclear cells (PBMC) KSHV DNA detection (P < or =
      .0001) and high KSHV lytic (>1:1745; P < or = .0001) and latent (>1:102,400; P =
      .03) antibody titers were found to be positively associated with CKS risk.
      Antibody titers were higher in cases with lesions compared with cases without
      lesions (P < or =.05). The detection of Epstein-Barr virus (EBV) DNA in PBMCs was
      not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS
      risk was found to be positively associated with reduced hematocrit (<37.4%; P =
      .03), hemoglobin (<12g/dL; P = .04), and lymphocytes (<1000 cells/microL; P =
      .004), including CD4-positive (+) cells (<457 cells/microL; P = .07) and CD8+
      cells (<213cells/microL; P = .04), and with increased monocytes (> or =638
      cells/microL; P = .009). Nonsignificant elevations of beta-2-microglobulin and
      neopterin were observed among cases regardless of disease burden (P > or = .08).
      In a multivariate model, the CKS risk was found to be associated with PBMC KSHV
      DNA (OR of 2.7; 95% CI, 1.4-5.3), a high KSHV lytic antibody titer (OR of 3.7;
      95% CI, 1.9-7.4), and low lymphocytes, particularly among those patients age <70
      years (OR of 8.0; 95% CI, 2.7-23.7). CONCLUSIONS: The findings of the current
      study appear to corroborate the specificity of KSHV and highlight the hematologic
      and immunologic correlates involved in the pathogenesis of CKS.

PMID- 16998934
TI  - Comprehensive classification of the auditory sensory projections in the brain of
      the fruit fly Drosophila melanogaster.
AB  - We established a comprehensive projection map of the auditory receptor cells
      (Johnston's organ neurons: JONs) from the antennae to the primary auditory center
      of the Drosophila brain. We found 477 +/- 24 cell bodies of JONs, which are
      arranged like a "bottomless bowl" within the auditory organ. The target of the
      JONs in the brain comprises five spatially segregated zones, each of which is
      contributed by bundles of JON axons that gradually branch out from the antennal
      nerve. Four zones are confined in the antennal mechanosensory and motor center,
      whereas one zone further extends over parts of the ventrolateral protocerebrum
      and the subesophageal ganglion. Single-cell labeling with the FLP-out technique
      revealed that most JONs innervate only a single zone, indicating that JONs can be
      categorized into five groups according to their target zones. Within each zone,
      JONs innervate various combinations of subareas. We classified these five zones
      into 19 subareas according to the branching patterns and terminal distributions
      of single JON axons. The groups of JONs that innervate particular zones or
      subareas of the primary auditory center have their cell bodies in characteristic
      locations of the Johnston's organ in the antenna, e.g., in concentric rings or in
      paired clusters. Such structural organization suggests that each JON group, and
      hence each zone of the primary auditory center, might sense different aspects of
      sensory signals.

PMID- 16998935
TI  - Ovarian small cell carcinoma of the hypercalcemic type in children and
      adolescents: a prognostically unfavorable but curable disease.
AB  - BACKGROUND: Ovarian small cell carcinoma of the hypercalcemic type is a rare
      neoplasm that is associated with a poor prognosis. The objective of the current
      study was to investigate the clinicopathologic features of this tumor and to
      develop preliminary diagnostic and therapeutic guidelines. METHODS: Between 1994
      and 2005, 11 girls (ages 9-22 years) who were registered on the German Maligne
      Keimzelltumoren studies and the Kiel Pediatric Tumor Registry were analyzed.
      Prior to histopathologic review, 8 patients had been misdiagnosed with either
      germ cell tumor or juvenile granulosa cell tumor. RESULTS: According to the
      International Federation of Gynecologic Oncology, 4 patients had Stage IA
      disease, 3 patients had Stage IC disease, and 4 patients had Stage III disease.
      After resection, 4 patients were followed without additional therapy, and all 4
      patients developed recurrent disease after 3 to 11 months. Seven patients
      received adjuvant chemotherapy during first-line treatment. One patient with
      Stage III disease received additional regional deep hyperthermia. During first
      line treatment, high-dose chemotherapy was received by 4 patients who achieved a
      complete response (CR) after conventional chemotherapy. All 4 of those patients
      remained in CR for 7 to 73 months, whereas the other 3 patients developed
      recurrent disease. Salvage treatment after recurrence or tumor progression
      consisted of surgery and chemotherapy. One patient received high-dose
      chemotherapy in 2nd CR and remained in 2nd CR. In total, 5 patients remained
      alive with no evidence of disease. CONCLUSIONS: Patients with ovarian small cell
      carcinoma of the hypercalcemic type require multiagent chemotherapy during first
      line treatment. High-dose chemotherapy may be used to consolidate the therapeutic
      success.

PMID- 16998936
TI  - In utero exposure to diethylstilbestrol (DES) does not increase genomic
      instability in normal or neoplastic breast epithelium.
AB  - BACKGROUND: In 1992, the National Cancer Institute (NCI) established the
      Continuation of Follow-Up of DES-Exposed Cohorts to study the long-term health
      effects of exposure to diethylstilbestrol (DES). Genetic effects on human breast
      tissue have not been examined. The authors investigated whether breast tissue of
      women exposed in utero to DES might exhibit the genetic abnormalities that
      characterize other DES-associated tumors. METHODS: Subjects enrolled in the NCI
      Cohort were queried about breast biopsies or breast cancer diagnoses. Available
      tissue blocks were obtained for invasive cancers (IC), in situ cancers (CIS), or
      atypical hyperplasia (AH). Exposure status was blinded, lesions were
      microdissected, and their DNA was analyzed for microsatellite instability (MI)
      and loss of heterozygosity (LOH), or allele imbalance (AI), at 20 markers on 9
      chromosome arms. RESULTS: From 31 subjects (22 exposed, 9 unexposed), 273 samples
      were analyzed (167 normal epithelium, 16 AH, 30 CIS, 60 IC). Exposed and
      unexposed subjects exhibited no differences in breast cancer risk factors or
      demographic characteristics, except for age at diagnosis (exposed vs. unexposed:
      43.2 vs. 48.8 years of age, P = .02). The authors found that MI was rare and that
      AI was common, with frequencies consistent with previous reports. The global age
      adjusted relative rate (RR) of AI was 1.3, 95% CI = 0.8-2.4. No statistically
      significant associations were observed after adjustment for risk factors or after
      stratification by histology or by chromosome arm. CONCLUSIONS: In utero DES
      exposure does not appear to significantly increase genomic instability in breast
      epithelium, as measured by MI and AI. Breast tissue may respond differently from
      that of the reproductive tract to in utero DES exposure. Consequences of in utero
      DES exposure on the breast may be mediated by proliferative effects of estrogen.

PMID- 16998937
TI  - Malignant phyllodes tumor of the female breast: association of primary therapy
      with cause-specific survival from the Surveillance, Epidemiology, and End Results
      (SEER) program.
AB  - BACKGROUND: Malignant phyllodes tumor is a rare and potentially aggressive breast
      neoplasm. Little information is available regarding the optimal management of
      these lesions and rarer still are data regarding survival. The current study used
      a large population database to determine prognostic factors that predict cause
      specific survival (CSS). METHODS: Data were obtained from the Surveillance,
      Epidemiology, and End Results Program (SEER) for the years 1983-2002. Women
      receiving resection for primary nonmetastatic malignant phyllodes tumor of the
      breast were included (n = 821). Analyses of patient, pathologic, and treatment
      characteristics were performed using univariate and multivariate Cox regression
      analyses for the CSS endpoint. RESULTS: With a median follow-up of 5.7 years, CSS
      was 91%, 89%, and 89%, at 5, 10, and 15 years, respectively. Mastectomy was
      performed in 428 women (52%) and wide excision or lumpectomy in 393 (48%). Women
      undergoing mastectomy were significantly older (P = .004) and had larger tumors
      (P = .009). Wide excision was associated with equivalent or improved CSS relative
      to mastectomy on univariate and multivariate analyses. Older age predicted for
      cause-specific mortality on multivariate analysis. Adjuvant radiotherapy (RT)
      predicted for worse CSS when implemented compared with surgery alone.
      CONCLUSIONS: Mastectomy was not found to provide a benefit in CSS compared with
      wide excision in malignant phyllodes tumor of the breast. Women undergoing wide
      excision had at the minimum similar cancer-specific mortality compared with those
      who received mastectomy. The role of adjuvant RT is uncertain and requires
      further investigation.

PMID- 16998938
TI  - Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a
      sensitive guaiac-based fecal occult blood test in detection of colorectal
      neoplasia.
AB  - BACKGROUND: Fecal immunochemical tests (FIT) are an advanced fecal occult blood
      test (FOBT) technology that reduces barriers to population screening by
      simplifying the logistics of stool-sampling. The current study was conducted to
      undertake a paired comparison of a sensitive guaiac FOBT (GFOBT; Hemoccult II
      Sensa, Beckman Coulter, Fullerton, CA) with a brush-sampling FIT (InSure;
      Enterix, North Ryde, NSW, Australia), to determine whether this FIT improves
      detection of significant neoplasia. METHODS: Individuals sampled consecutive
      stools, at home, with both FIT and GFOBT sampling devices while following dietary
      restrictions appropriate for GFOBT. Study populations included a screening cohort
      (n = 2351) and a symptomatic diagnostic group (n = 161). Paired comparison of
      positivity rates was undertaken in those found to have cancer and/or significant
      adenoma (high-grade dysplasia, villous change, > or =10 mm, serrated histology or
      > or =3 polyps), benign pathology, or no pathology. RESULTS: Combined results for
      both cohorts showed that the FIT returned a true-positive result significantly
      more often in cancer (n = 24; 87.5% vs. 54.2%) and in significant adenomas (n =
      61; 42.6% vs. 23.0%). Of all UICC Stage I cancers, the FIT was positive in 12 of
      13 compared with 4 of 13 with the GFOBT (P = .002). In analyses of just the
      screening cohort, the FIT remained significantly better at detecting cancers and
      significant adenomas; the false-positive rate for any neoplasia was marginally
      higher with the FIT than the GFOBT (3.4% vs. 2.5%; 95% CI of difference, 0-1.8%),
      whereas positive predictive values were 41.9% and 40.4%, respectively.
      CONCLUSIONS: This brush-sampling FIT is more sensitive for cancers and
      significant adenomas than a sensitive GFOBT. As such, it should deliver greater
      reductions in colorectal cancer mortality and incidence than the GFOBT.

PMID- 16998939
TI  - Comparative mapping of serotonin-immunoreactive neurons in the central nervous
      systems of nudibranch molluscs.
AB  - The serotonergic systems in nudibranch molluscs were compared by mapping the
      locations of serotonin-immunoreactive (5-HT-ir) neurons in 11 species
      representing all four suborders of the nudibranch clade: Dendronotoidea (Tritonia
      diomedea, Tochuina tetraquetra, Dendronotus iris, Dendronotus frondosus, and
      Melibe leonina), Aeolidoidea (Hermissenda crassicornis and Flabellina trophina),
      Arminoidea (Dirona albolineata, Janolus fuscus, and Armina californica), and
      Doridoidea (Triopha catalinae). A nomenclature is proposed to standardize reports
      of cell location in species with differing brain morphologies. Certain patterns
      of 5-HT immunoreactivity were found to be consistent for all species, such as the
      presence of 5-HT-ir neurons in the pedal and cerebral ganglia. Also, particular
      clusters of 5-HT-ir neurons in the anterior and posterior regions of the dorsal
      surface of the cerebral ganglion were always present. However, there were
      interspecies differences in the number of 5-HT-ir neurons in each cluster, and
      some clusters even exhibited strong intraspecies variability that was only weakly
      correlated with brain size. Phylogenetic analysis suggests that the presence of
      particular classes of 5-HT-ir neurons exhibits a great deal of homoplasy. The
      conserved features of the nudibranch serotonergic system presumably represent the
      shared ancestral structure, whereas the derived characters suggest substantial
      independent evolutionary changes in the number and presence of serotonergic
      neurons. Although a number of studies have demonstrated phylogenetic variability
      of peptidergic systems, this study suggests that serotonergic systems may also
      exhibit a high degree of homoplasy in some groups of organisms.

PMID- 16998940
TI  - JAK2 (V617F) as an acquired somatic mutation and a secondary genetic event
      associated with disease progression in familial myeloproliferative disorders.
AB  - BACKGROUND: A somatic gain-of-function mutation of the Janus kinase 2 (JAK2) gene
      has been identified in chronic myeloproliferative disorders, which appear to have
      a sporadic occurrence in most individuals. The authors studied the biologic
      significance of the JAK2 (V617F) mutation in familial myeloproliferative
      disorders. METHODS: Twenty pedigrees with familial chronic myeloproliferative
      disorders were identified through an investigation of family history in 264
      patients with sporadic myeloproliferative disorders. A quantitative real-time
      polymerase chain reaction (qRT-PCR)-based allelic discrimination assay was
      employed for the detection of the V617F mutation in circulating granulocytes and
      T lymphocytes. An analysis of X-chromosome inactivation pattern was performed in
      female patients. RESULTS: Fourteen families had homogeneous phenotypes, and 6
      families had mixed phenotypes. By using a qRT-PCR-based allelic discrimination
      assay, the JAK2 (V617F) mutation was detected in circulating granulocytes from 20
      of 31 patients, but the mutation was not detected in T lymphocytes. Granulocyte
      mutant alleles ranged from 2.1% to 91.5% and, on average, increased with time.
      Discordant distribution of the JAK2 (V617F) mutation was observed in siblings
      with polycythemia vera. The proportion of granulocytes that carried the JAK2
      (V617F) mutation was lower than the proportion of clonal granulocytes, as
      determined in an analysis of X-chromosome inactivation patterns in female
      patients. CONCLUSIONS: The current findings indicated that the JAK2 (V617F)
      mutation represents an acquired somatic mutation in patients with familial
      chronic myeloproliferative disorders and probably occurs as a secondary genetic
      event in the background of preexisting clonal hematopoiesis. Thus, a genetic
      predisposition to acquisition of JAK2 (V617F) is inherited in families with
      myeloproliferative disorders.

PMID- 16998941
TI  - Capillary physiology of human medulloblastoma: impact on chemotherapy.
AB  - BACKGROUND: Advances in the treatment of medulloblastoma have largely been
      attributed to the introduction of chemotherapy, although Phase III trials have
      shown advantages for chemotherapy only in subgroups. Because the efficacy of
      chemotherapy depends on tumor vascularization, the vascular physiology of human
      medulloblastomas was evaluated. METHODS: Seven patients with histologically
      proven medulloblastomas underwent measurements of capillary permeability and
      vascular plasma volume using contrast-enhanced dynamic computer tomography.
      Regional blood flow was measured in 5 patients using xenon computed tomography
      (CT). RESULTS: The capillary permeability-surface product for water-soluble
      compounds ranged from 1.7 +/- 5.5 to 17.6 +/- 12.3 muL/g/min with a mean of 10.5
      +/- 6.3 microL/g/min. The vascular plasma volume ranged from 0.02 +/- 0.021 to
      0.045 +/- 0.049 mL/g with a mean of 0.03 +/- 0.01 mL/g. The efflux rate ranged
      from 0.012 +/- 0.007 to 0.065 +/- 0.064 1/min with a mean of 0.039 +/- 0.020
      1/min. Regional tumoral blood flow showed a mean of 19.86 +/- 6.8 mL/100g/min as
      compared with normal cerebellum with 45.4 +/- 12.03 mL/100g/min (P < .005).
      CONCLUSIONS: The current study demonstrated a low capillary permeability and
      blood flow in medulloblastomas that could explain the limited response rates of
      partially resected tumors even after aggressive high-dose chemotherapy, as
      recently reported.

PMID- 16998942
TI  - Changes in surgical management resulting from case review at a breast cancer
      multidisciplinary tumor board.
AB  - BACKGROUND: The treatment of breast cancer requires a multidisciplinary approach,
      and patients are often referred to a multidisciplinary cancer clinic. The purpose
      of the current study was to evaluate the impact of this approach on the surgical
      management of breast cancer. METHODS: The medical records of 149 consecutive
      patients referred to a multidisciplinary breast cancer clinic over a 1-year
      period with a diagnosis of breast cancer were reviewed retrospectively for
      alterations in radiologic, pathologic, surgical, and medical interpretations and
      the effect that these alterations had on recommendations for surgical management.
      RESULTS: A review of the imaging studies resulted in changes in interpretations
      in 67 of the 149 patients studied (45%). This resulted in a change in surgical
      management in 11% of patients. Review of the pathology resulted in changes in the
      interpretation for 43 of the 149 patients (29%). Thirteen patients (9%) had
      surgical management changes made solely as a result of pathologic
      reinterpretation. In 51 patients (34%), a change in surgical management was
      recommended after discussion with the surgeons, medical oncologists, and
      radiation oncologists that was not based on reinterpretation of the radiologic or
      pathologic findings. Overall, a second evaluation of patients referred to a
      multidisciplinary tumor board led to changes in the recommendations for surgical
      management in 77 of 149 of those patients studied (52%). CONCLUSIONS: The changes
      in management stemmed from differences in mammographic interpretation, pathologic
      interpretation, and evaluation by medical and radiation oncologists and surgical
      breast specialists. Multidisciplinary review can provide patients with useful
      additional information when making difficult treatment decisions.

PMID- 16998944
TI  - Stop the press-or at least stop the medication.

PMID- 16998945
TI  - Use of beta-2 agonists and risk of hip/femur fracture: a population-based case
      control study.
AB  - INTRODUCTION: Administration of beta-2 agonists decreased bone mineral density in
      rats. But the association between bronchodilators and fracture risk has not been
      studied in humans. OBJECTIVES: To examine the association between use of beta-2
      agonists and risk of hip/femur fracture. METHODS: We conducted a population-based
      case-control study (6763 cases) in the Dutch PHARMO database. Current beta-2
      agonist use was compared to never use. We adjusted for severity of the underlying
      respiratory disease and disease and drug history. RESULTS: A hospitalisation for
      asthma/COPD in the year before index date increased risk of hip/femur fracture:
      crude OR 2.17 (95% CI, 1.41-3.34). Patients using higher doses of beta-2 agonists
      had increased risk of hip/femur fracture: crude OR 1.94 (95% CI, 1.41-2.66) for
      daily dosages of >or=1600 microg albuterol equivalent. The excess fracture risk
      reduced after adjustment for disease severity (1.46; 95% CI, 1.02-2.08) and after
      exclusion of oral glucocorticoid users (1.31; 95% CI, 0.80-2.15). Risk of
      hip/femur fracture was similar between users of beta-2 agonists, inhaled
      glucocorticoids and anticholinergics. CONCLUSION: We found increases in the risk
      of hip/femur fracture in patients using higher doses of beta-2 agonists. However,
      the excess risk of hip/femur fracture substantially reduced after exclusion of
      oral glucocorticoid users and after adjustment for the underlying disease. Risk
      of hip/femur fracture was similar between users of beta-2 agonists, inhaled
      glucocorticoids and anticholinergics. The severity of the underlying disease,
      rather than the use of beta-2 agonists, may play an important role in the
      aetiology of hip/femur fractures in patients using beta-2 agonists.

PMID- 16998947
TI  - Reporting adverse events in randomized controlled trials.
AB  - PURPOSE: How randomized controlled trial results are reported may minimize
      concerns and detection of adverse side effects. We aimed to describe the methods
      of reporting adverse events in these published trials. METHODS: Five frequently
      cited journals were investigated: Annals of Internal Medicine, British Medical
      Journal, JAMA, The Lancet, and the New England Journal of Medicine. For each
      journal, all randomized controlled trials conducted on the use of a medication
      were selected from January 2000 through June 2003. All issues of each journal
      were reviewed manually. Information retrieved included any mention of adverse
      events in the abstract, methods, results, or discussion section of the article;
      or inclusion of adverse events data in tables or figures. We also cataloged
      whether there was a separate subheading in the results section for reporting
      adverse events. Reports of trials that referred to methods described in a
      previous report were excluded. RESULTS: There were 521 eligible articles.
      Explicit mention of adverse events was in 328 (63%) of abstracts (range 47-66%),
      380 (73%) of methods (range 51-81%), 464 (89%) of results (range 80-95%), and 250
      (48%) of tables (range 31-49%). There was a separate subheading for adverse
      events in 240 (46%) (range 22-64%) of the eligible articles. CONCLUSION: There is
      variation among authors and journals as to the location of reporting adverse
      events and the means by which it is done. Authors and editors should include
      specific information on adverse events when reporting the results of randomized
      controlled trials. It would be ideal if there was more consistency among authors
      and journals as to how these adverse events are described.

PMID- 16998946
TI  - Effectiveness of two statin prescribing strategies with respect to adherence and
      cardiovascular outcomes: observational study.
AB  - BACKGROUND: There is considerable evidence that statins can reduce cardiovascular
      events. Currently high-risk patients are treated to a target cholesterol
      concentration. An alternative prescribing strategy (the 'fire-and-forget'
      approach) would instead deploy low-dose statins more widely. It has been
      suggested that for the same cost this approach might prevent more cardiovascular
      events. We have compared the treat-to-target and fire-and-forget statin
      prescribing strategies with respect to adherence and cardiovascular outcomes.
      METHODS: We used a population-based record-linkage database containing several
      data sets linked by a unique patient identifier. We identified two cohorts of
      patients. Patients in the treat-to-target cohort were prescribed a statin, and
      subsequent measurement of their cholesterol was followed by upward titration of
      their statin dose if necessary. Patients in the fire-and-forget cohort were
      prescribed a statin, but no further cholesterol measurement was observed during
      the follow-up period. FINDINGS: Adherence to statin treatment in patients treated
      to target was significantly better than in patients treated on a fire-and-forget
      basis (adjusted odds ratio 2.51, 95%CI 2.26-2.78). We found a lower
      cardiovascular disease (CVD) event rate in patients treated to target than in
      fire-and-forget patients (hazard ratio of CVD or cardiovascular death 0.41 (0.35
      0.48) even after adjustment was made for adherence and baseline CVD risk).
      INTERPRETATION: Our findings suggest that adherence to statins is worse in
      patients treated on a fire-and-forget basis than in patients treated to a target
      cholesterol concentration, and that this prescribing strategy is associated with
      worse cardiovascular outcomes.

PMID- 16998948
TI  - Preferences of cancer patients regarding the disclosure of bad news.
AB  - To understand patients' preferences regarding the disclosure of bad news is
      important in the clinical oncology setting. The aim of this study was to clarify
      descriptively the preferences of cancer patients. Five hundred and twenty-nine
      Japanese cancer outpatients were surveyed regarding their preferences regarding
      the disclosure of bad news, and several psychosocial and medical demographic
      variables were analyzed. In a descriptive analysis, more than 90% of the patients
      strongly preferred to discuss their current medical condition and treatment
      options with their physician and to have their physicians take the feelings of
      their family into consideration as well. While half of the patients preferred to
      receive information regarding their life expectancy, 30% preferred not to receive
      it. Multiple regression analyses indicated the preferences showing
      interindividual variations were associated with the level of education and the
      mental adjustment to cancer scores. A factor analysis revealed four preferences
      factors: method of disclosure of the bad news, provision of emotional support,
      provision of additional information, and setting. These four factors had good
      internal consistency reliability (Cronbach's alpha = 0.93-0.77). Providing
      emotional support, including the desire for the physician to show consideration
      for the patient's family, and understanding an individual's communication
      preferences may be useful for promoting patient-physician communication.

PMID- 16998949
TI  - Complete blindness after optic neuropathy induced by short-term linezolid
      treatment in a patient suffering from muscle dystrophy.
AB  - We present a case of severe optic neuropathy following linezolid treatment, which
      led to complete irreversible blindness, in a patient with progressive muscular
      dystrophy, treated with linezolid for 16 days for methicillin-resistant
      Staphylococcus aureus (MRSA) pneumonia. Interruption of antibiotic therapy did
      not lead to remission of ocular symptoms. Administration of linezolid may lead to
      severe neuropathy even in the case of short-term treatment.

PMID- 16998950
TI  - The impact of parental cancer on the adolescent: an analysis of the literature.
AB  - Research has revealed the impact of the diagnosis of cancer on an individual,
      their spouse, and their family. One dimension that has received little attention
      is the impact of the cancer diagnosis on the patient's adolescent. This article
      offers an analysis of descriptive studies, intervention studies, and databased
      book chapters, published between 1966 and 2006, that examined the impact of
      parental cancer on the adolescent. The results of 45 studies and three databased
      book chapters are organized around four themes: adolescents' (1) emotions and
      behaviors (2) perceptions and knowledge of parental cancer (3) changes in roles
      and (4) ways of coping. These themes will assist the reader in understanding the
      application of the knowledge gained from the analysis of the literature to
      directions for future research.

PMID- 16998951
TI  - Evaluating SPIO-labelled cell MR efficiency by three-dimensional quantitative T2*
      MRI.
AB  - An in vitro MR-assay for superparamagnetic iron oxide (SPIO) particle cell
      labelling assessment via three-dimensional quantitative T(2) (*) MR microscopy
      was proposed. On high-resolution images, and due to the high susceptibility
      difference between the particles and the surrounding medium, SPIO internalized in
      cells induces signal loss which may be counted and measured on T(2) (*) maps. The
      increase in both labelled cell percentage and the average perturbation volume
      with an added amount of iron in the incubation medium proved that intracellular
      iron uptake is dependent upon the initial concentration of incubation iron. It
      also proved that the observed increases in total cellular iron uptake measured by
      inductively coupled plasma optical emission spectroscopy are due to both an
      increase in the iron mass per cell and also an increase in labelled cell
      concentration. MR results were compared with Prussian blue staining histology.
      The sensitivity of the MR methodology was then used to distinguish labelling
      differences for two different types of particle coating. The MRI-assay we
      proposed is a compulsory tool to optimize labelling efficiency in order to
      improve in vivo cell detection. Key parameters for detection, such as the
      percentage of cell labelling, the effect on the image for a given amount of
      internalized iron and labelling distribution among a cell population, are easily
      obtained. The comparison of different contrast agents for labelling one cell
      type, the assessment of one type of contrast agent for labelling different cell
      types and/or the evaluation of labelling strategies, are possible without having
      recourse to classical methods, and provide improved accuracy, since the principle
      is based on intracellular relaxivity.

PMID- 16998952
TI  - Improved visualization of non-transmural scar using slice-selective inversion
      recovery delayed contrast-enhanced MRI: a preliminary report.
AB  - Delayed contrast-enhanced MRI (ce-MRI) pulse sequence is a promising modality for
      the assessment of myocardial viability. However, conventional ce-MRI using a non
      selective inversion recovery (IR) pulse can often yield poor edge definition or
      contrast-to-noise ratio (CNR) between the non-transmural scar and blood (i.e. the
      blood and scar appear isointense). Subtraction and multicontrast ce-MRI methods
      can be used to improve the CNR between the non-transmural scar and blood, but
      they require two image acquisitions. The authors have developed a single
      acquisition ce-MRI pulse sequence that utilizes a slice-selective IR pulse to
      generate bright-blood contrast using inflow effects for an improved edge
      definition between the non-transmural scar and blood. Six patients with
      myocardial infarction were imaged at 1.5 T using both non-selective and slice
      selective IR ce-MRI acquisitions with identical imaging parameters. The CNR
      between the non-transmural scar and normal myocardium was not different between
      the two acquisitions. The CNR between the blood and non-transmural scar (16.9 +/-
      12.3 versus 3.2 +/- 7.9; p < 0.001) was significantly higher for the slice
      selective IR acquisition than for the non-selective IR acquisition. This study
      demonstrates the feasibility of using a slice-selective IR pulse to improve the
      visualization of a non-transmural scar in ce-MRI, without increasing the
      acquisition time.

PMID- 16998953
TI  - Transverse relaxation in rat optic nerve.
AB  - In vitro investigations were performed to study the proton T(2) relaxation
      spectrum of rat optic nerve. Studies in which the nerve was incubated in a D(2)O
      based solution revealed that >98% of the spectrum originated from the water
      protons. The spectrum was found to consist of three components having relaxation
      times and sizes similar to those reported in the literature for peripheral nerve.
      Procedures were taken to confirm the existence of a third optic nerve component
      and that it was not an artifact of the long-lived water protons of the in vitro
      incubation solution. Evidence using paramagnetic agents in the incubation
      solution, which removed the two longest-lived nerve components from the spectrum,
      revealed the existence of a small fourth component (<10% of total) having a T(2)
      relaxation time similar to that of the intermediate-lived nerve component.
      Bathing the nerves in a 10 mM glutamate solution, glutamate known to result in
      cellular swelling in mammalian central nervous system (CNS), was found to
      increase the component size of the longest-lived nerve component, suggestive that
      this component may result from cellular water.

PMID- 16998954
TI  - Retrospective cine 3He ventilation imaging under spontaneous breathing
      conditions: a non-invasive protocol for small-animal lung function imaging.
AB  - A non-invasive and free-breathing hyperpolarized (HP) (3)He imaging protocol for
      small animals was implemented and validated on rats for lung function imaging.
      Animals were allowed to breathe a mixture of air and (3)He from a mask and a gas
      reservoir fitted to their heads. Radial imaging sequences were used, and MRI
      signal intensity changes were monitored for retrospective cine image
      reconstruction. The ventilation cycle of the animals was imaged with a 100 ms
      temporal resolution. The sliding window imaging technique was applied to
      reconstruct 5 ms time-shifted image series covering the complete breathing cycle.
      Image series were processed to extract quantitative ventilation parameters such
      as the gas arrival time. The reproducibility and the non-invasiveness of this
      ventilation imaging protocol were evaluated by multiple acquisitions on the same
      animals.

PMID- 16998955
TI  - New hope for RCC patients.

PMID- 16998956
TI  - STAR trial reports.

PMID- 16998957
TI  - Glivec and beyond.

PMID- 16998958
TI  - Joan Wright Goodman.

PMID- 16998959
TI  - Cancer in the young: the baseline.

PMID- 16998960
TI  - [In focus: adiposity]].

PMID- 16998962
TI  - [The 99th annual meeting of the Japanese Society of Animal Reproduction. Nagoya,
      Japan. September 7-9, 2006. Abstracts].

PMID- 16998961
TI  - [In focus: adiposity].

PMID- 16998963
TI  - Top-down vs. bottom-up effects in kelp forests.

PMID- 16998964
TI  - Stimulatory autoantibodies to the PDGF receptor in scleroderma.

PMID- 16998965
TI  - ACE inhibitors and major congenital malformations.

PMID- 16998966
TI  - Omalizumab for asthma.

PMID- 16998967
TI  - Obesity and public health law.

PMID- 16998968
TI  - Catheter ablation for chronic atrial fibrillation.

PMID- 16998970
TI  - Transcription and translation of RNA.

PMID- 16998969
TI  - DNA Commission of the International Society of Forensic Genetics (ISFG): an
      update of the recommendations on the use of Y-STRs in forensic analysis.
AB  - The DNA Commission of the International Society of Forensic Genetics (ISFG)
      regularly publishes guidelines and recommendations concerning the application of
      DNA polymorphisms to the problems of human identification. A previous
      recommendation published in 2001 has already addressed Y-chromosome
      polymorphisms, with particular emphasis on short tandem repeats (STRs). Since
      then, the use of Y-STRs has become very popular, and numerous new loci have been
      introduced. The current recommendations address important aspects to clarify
      problems regarding the nomenclature, the definition of loci and alleles,
      population genetics and reporting methods

PMID- 16998971
TI  - Gene therapy.

PMID- 16998972
TI  - T-cell activation.

PMID- 16998973
TI  - Screening a DNA library for specific clones.

PMID- 16998974
TI  - The structure of an antibody molecule.

PMID- 16998975
TI  - Gene activation by interferon.

PMID- 16998976
TI  - Illuminant and observer metamerism and the Hardy-Rand-Rittler color vision test
      editions.
AB  - A previous study identified a significant metamerism in the several editions of
      the Hardy-Rand-Rittller pseudoisochromatic plates (HRR) but did not proceed to
      quantify the consequences of that metamerism (Dain, 2004). Metamerism arises from
      two sources and is almost inevitable when a printed color vision test is
      reproduced in several editions. Metamerism has two consequences; these are
      illuminant/source-based changes in performance and changes in performance with
      observer (less well known) when assessing anomalous trichromats. This study
      addresses the effects of illuminant/source and observer metamerism on the fourth
      editions of HRR. Groups of colors intended to lie on a dichromat confusion line
      generally remain on a confusion line when the source id changed. The plates
      appear to be resistant to each form of metamerism, perhaps because the features
      of the spectral reflectance are similar for figure color and background gray. As
      a consequence, the clinician needs to be less concerned about using a non
      recommended source than was previously believed.

PMID- 16998977
TI  - Civil commitment in New York City: an analysis of practice.

PMID- 16998978
TI  - Analytical performance criteria. The need for an international sampling
      convention for inhalable dust in calm air.

PMID- 16998979
TI  - Substituted judgement and the right to refuse shock treatment in Washington: In
      re Schuoler.

PMID- 16998980
TI  - The health care agent: protecting the choices and interests of patients who lack
      capacity.

PMID- 16998981
TI  - 2006 Donald E. Cummings Memorial Award Lecture. Industrial Hygiene: the founders,
      the pioneers, and the next generation.

PMID- 16998982
TI  - [Tachykinin receptors--the role in gastrointestinal diseases].

PMID- 16998983
TI  - Globalization of the profession of industrial hygiene: development work, micro
      and small enterprises, and the informal economy.

PMID- 16998984
TI  - Ethical problems for physicians raised by AIDS and HIV infection: conflicting
      legal obligations of confidentiality and disclosure.

PMID- 16998985
TI  - Diacetyl emissions and airborne dust from butter flavorings used in microwave
      popcorn production.
AB  - In microwave popcorn workers, exposure to butter flavorings has been associated
      with fixed obstructive lung disease resembling bronchiolitis obliterans.
      Inhalation toxicology studies have shown severe respiratory effects in rats
      exposed to vapors from a paste butter flavoring, and to diacetyl, a diketone
      found in most butter flavorings. To gain a better understanding of worker
      exposures, we assessed diacetyl emissions and airborne dust levels from butter
      flavorings used by several microwave popcorn manufacturing companies. We heated
      bulk samples of 40 different butter flavorings (liquids, pastes, and powders) to
      approximately 50 degrees C and used gas chromatography, with a mass selective
      detector, to measure the relative abundance of volatile organic compounds
      emitted. Air sampling was conducted for diacetyl and for total and respirable
      dust during the mixing of powder, liquid, or paste flavorings with heated soybean
      oil at a microwave popcorn plant. To further examine the potential for
      respiratory exposures to powders, we measured dust generated during different
      simulated methods of manual handling of several powder butter flavorings. Powder
      flavorings were found to give off much lower diacetyl emissions than pastes or
      liquids. The mean diacetyl emissions from liquids and pastes were 64 and 26 times
      larger, respectively, than the mean of diacetyl emissions from powders. The
      median diacetyl emissions from liquids and pastes were 364 and 72 times larger,
      respectively, than the median of diacetyl emissions from powders. Fourteen of 16
      powders had diacetyl emissions that were lower than the diacetyl emissions from
      any liquid flavoring and from most paste flavorings. However, simulated handling
      of powder flavorings showed that a substantial amount of the airborne dust
      generated was of respirable size and could thus pose its own respiratory hazard.
      Companies that use butter flavorings should consider substituting flavorings with
      lower diacetyl emissions and the use of ventilation and enclosure engineering
      controls to minimize exposures. Until controls are fully implemented, companies
      should institute mandatory respiratory protection for all exposed workers.

PMID- 16998986
TI  - [Vasopressin receptors].

PMID- 16998987
TI  - Challenges of the new biotechnology.

PMID- 16998988
TI  - Particle characteristics in the reactor and pelletizing areas of carbon black
      production.
AB  - Physical and chemical characteristics of airborne particles (ultrafine, PM1,
      PM2.5, and PM10) in reactor and pelletizing areas during carbon black production
      were measured to assess process related sources of particles in work areas.
      Results from bagging areas within the same three facilities have been previously
      published. Particle number and mass concentration measurements were conducted in
      these work areas and at ambient comparison sites at each of the three carbon
      black plants. No elevated ultrafine particle number concentrations (UFP, <100 nm)
      with respect to ambient were determined in the work areas of Plant 1,
      intermittently elevated concentrations at Plant 2, and permanently elevated
      concentrations at Plant 3. The intermittently elevated UFP concentrations in the
      pelletizer and reactor areas of Plant 2 could be related to nearby traffic
      emissions. The ultrafine particle number concentrations at Plant 2 are comparable
      to those determined at urban traffic sites. Both work areas of Plant 3 showed
      elevated UFP concentrations in the pelletizer reactor and areas. In the case of
      the reactor, which was the only enclosed reactor area investigated among the
      three facilities, the source of the elevated UFP number concentration was most
      likely attributable to grease and oil fumes from maintenance activities, a
      conclusion supported by carbon fractionation analysis. The elevated UFP number
      concentrations in the pelletizing area in this same plant are related to leaks in
      the production line, which allowed particulate matter to escape to the
      surrounding areas. Absolute PM10 mass concentrations were all within normal
      ambient concentrations except for the pelletizing area in Plant 3, which showed
      continuous levels above ambient. One additional source contributing to peak level
      PM10 mass concentrations at Plant 2 was due to wind dispersion from a carbon
      black spill incident the day prior to measurements. It is concluded from these
      measurements that no carbon black is released in the reactor and pelletizing
      areas (as UFP or PM10) from the closed production lines under normal operating
      conditions.

PMID- 16998989
TI  - [Chronopharmacology].

PMID- 16998990
TI  - The debate on surrogate motherhood: the current situation, some arguments and
      issues; questions facing law and policy.

PMID- 16998991
TI  - Rating exposure control using Bayesian decision analysis.
AB  - A model is presented for applying Bayesian statistical techniques to the problem
      of determining, from the usual limited number of exposure measurements, whether
      the exposure profile for a similar exposure group can be considered a Category 0,
      1, 2, 3, or 4 exposure. The categories were adapted from the AIHA exposure
      category scheme and refer to (0) negligible or trivial exposure (i.e., the true X
      0.95 < or =1%OEL), (1) highly controlled (i.e., X 0.95 < or =10%OEL), (2) well
      controlled (i.e., X 0.95 < or =50%OEL), (3) controlled (i.e., X 0.95 < or
      =100%OEL), or (4) poorly controlled (i.e., X0.95 > or =1%OEL) exposures. Unlike
      conventional statistical methods applied to exposure data, Bayesian statistical
      techniques can be adapted to explicitly take into account professional judgment
      or other sources of information. The analysis output consists of a distribution
      (i.e., set) of decision probabilities: e.g., 1%, 80%, 12%, 5%, and 2% probability
      that the exposure profile is a Category 0, 1, 2, 3, or 4 exposure. By inspection
      of these decision probabilities, rather than the often difficult to interpret
      point estimates (e.g., the sample 95th percentile exposure) and confidence
      intervals, a risk manager can be better positioned to arrive at an effective
      (i.e., correct) and efficient decision. Bayesian decision methods are based on
      the concepts of prior, likelihood, and posterior distributions of decision
      probabilities. The prior decision distribution represents what an industrial
      hygienist knows about this type of operation, using professional judgment;
      company, industry, or trade organization experience; historical or surrogate
      exposure data; or exposure modeling predictions. The likelihood decision
      distribution represents the decision probabilities based on an analysis of only
      the current data. The posterior decision distribution is derived by
      mathematically combining the functions underlying the prior and likelihood
      decision distributions, and represents the final decision probabilities.
      Advantages of Bayesian decision analysis include: (a) decision probabilities are
      easier to understand by risk managers and employees; (b) prior data, professional
      judgment, or modeling information can be objectively incorporated into the
      decision-making process; (c) decisions can be made with greater certainty; (d)
      the decision analysis can be constrained to a more realistic "parameter space"
      (i.e., the range of plausible values for the true geometric mean and geometric
      standard deviation); and (e) fewer measurements are necessary whenever the prior
      distribution is well defined and the process is fairly stable. Furthermore,
      Bayesian decision analysis provides an obvious feedback mechanism that can be
      used by an industrial hygienist to improve professional judgment. For example, if
      the likelihood decision distribution is inconsistent with the prior decision
      distribution then it is likely that either a significant process change has
      occurred or the industrial hygienist's initial judgment was incorrect. In either
      case, the industrial hygienist should readjust his judgment regarding this
      operation.

PMID- 16998993
TI  - Policy watch. Focus on the men?

PMID- 16998992
TI  - Maternal duties during pregnancy: toward a conceptual framework.

PMID- 16998994
TI  - R (On the application of Quintavalle) v Secretary of State for Health.

PMID- 16998995
TI  - R (on the application of Quintavalle) v Human Fertilisation and Embryology
      Authority.

PMID- 16998996
TI  - Leeds Teaching Hospitals NHS Trust v A.

PMID- 16998997
TI  - U v W (Attorney General intervening).

PMID- 16998998
TI  - Rose v Secretary of State for Health and Human Fertilisation and Embryology
      Authority.

PMID- 16999000
TI  - Increases in bone turnover found among bariatric surgery patients.

PMID- 16998999
TI  - Oral agents for type 2 diabetes reduce HbA1c, are weight neutral.

PMID- 16999001
TI  - The pathophysiology of joint infections.

PMID- 16999002
TI  - [Revising the nomenclature in psychiatry].

PMID- 16999003
TI  - National Survey of Family Growth, Cycle 6: sample design, weighting, imputation,
      and variance estimation.
AB  - OBJECTIVES: Cycle 6 of the National Survey of Family Growth (NSFG) was conducted
      by the National Center for Health Statistics in 2002 and early 2003. This report
      describes how the sample was designed, shows response rates for various subgroups
      of men and women, describes how the sample weights were computed to make national
      estimates possible, shows how missing data were imputed for a limited set of key
      variables, and describes the proper ways to estimate sampling errors from the
      NSFG. The report includes both nontechnical summaries for readers who need only
      general information and more technical detail for readers who need an in-depth
      understanding of these topics. METHODS: The NSFG Cycle 6 was based on an
      independent, national probability sample of men and women 15-44 years of age. It
      was the first NSFG ever to include a national sample of men 15-44 as well as a
      sample of women. Fieldwork was carried out by the University of Michigan's
      Institute for Social Research (ISR) under a contract with NCHS. In-person, face
      to-face interviews were conducted by professional female interviewers using
      laptop computers. In all, 12,571 women and men-7,643 females and 4,928 males-were
      interviewed, the largest NSFG ever done. RESULTS: Analysis of NSFG Cycle 6 data
      requires the use of sampling weights and estimation of sampling errors that
      accounts for the complex sample design and estimation features of the survey.
      Examples of how to use several available software packages that incorporate
      complex design features in estimation, such as SAS, SUDAAN, and STATA, are
      presented.

PMID- 16999004
TI  - A novel dentifrice technology for advanced oral health protection: A review of
      technical and clinical data.
AB  - Throughout the world, dentifrices have played a key role in the practice of good
      oral hygiene and promotion of better oral health. In addition to providing
      general dental cleaning, toothpastes also have served as an excellent vehicle for
      the introduction of new agents that deliver therapeutic and cosmetic benefits.
      Key examples of using dentifrices to provide added benefits include the
      introduction in 1955 of the first fluoridated toothpaste clinically proven to
      fight caries (Crest Cavity Protection) and the launch of the first tartar-control
      dentifrice (Crest Tartar Control) in the mid-1980s. To continue expanding the
      health and esthetic benefits offered by a single dentifrice, a multitude of
      agents have been investigated over the past 3 decades. The focus of these
      investigations has been in the multibenefit segment, the most widely used among
      US consumers.

PMID- 16999005
TI  - Antigingivitis efficacy of a stabilized stannous fluoride/sodium
      hexametaphosphate dentifrice in subjects previously nonresponsive to a
      triclosan/copolymer dentifrice.
AB  - Antimicrobial agents, such as stannous fluoride and triclosan, have been
      incorporated into dentifrice formulations and shown to be effective in the
      prevention and reduction of gingivitis. However, not all subjects respond to
      treatment. The objective of this study was to assess the antigingivitis efficacy
      of a 0.454% stannous fluoride/sodium hexametaphosphate dentifrice among subjects
      who were identified as nonresponsive or minimally responsive to a sodium
      fluoride/triclosan/copolymer dentifrice. This was a 12-week, examiner-blind,
      single-center study. Forty-one subjects with no or minimal gingivitis response to
      6 months of use of a sodium fluoride/triclosan/copolymer dentifrice were enrolled
      in this study and 38 of them provided complete data. All subjects were provided
      with a 0.454% stannous fluoride/sodium hexametaphosphate dentifrice to use over
      the next 3 months (12 weeks). Subjects were instructed to brush twice daily for
      60 seconds using their assigned product. Toothbrushing was supervised for 3 days
      of each week. Clinical examinations using the Loe-Silness Gingival Index were
      performed at 6 and 12 weeks posttreatment. The 6-month scores after the use of
      the sodium fluoride/triclosan/copolymer dentifrice served as the baseline. After
      12 weeks of product use, participants had statistically significantly less
      gingivitis by 54% and statistically significantly less bleeding by 55% on average
      compared to baseline. No adverse oral soft tissue effects were reported in the
      study. This study demonstrated that the use of an experimental 0.454% stannous
      fluoride/sodium hexametaphosphate dentifrice over a 12-week period provides a
      statistically significant and clinically relevant effect in the control of
      gingivitis among subjects who previously did not respond to 6 months of use of a
      sodium fluoride/triclosan/copolymer dentifrice.

PMID- 16999006
TI  - Sustained antibacterial actions of a new stabilized stannous fluoride dentifrice
      containing sodium hexametaphosphate.
AB  - Stannous fluoride has been used as a chemotherapeutic agent for years to improve
      oral health. The benefits of stannous fluoride in controlling caries, plaque, and
      gingivitis are directly associated with its antimicrobial actions. Recently, a
      novel dentifrice was developed that combines stannous fluoride with an
      anticalculus agent, sodium hexa. metaphosphate. A series of independent
      evaluations were conducted to assess the long-lasting antimicrobial activity of
      stannous fluoride in the new stannous fluoride/sodium hexametaphosphate
      dentifrice: an in vitro Live/Dead assay; an in vivo Plaque Glycolysis and
      Regrowth Model study; a rapid in vitro salivary bacteria metabolic activity
      study; and a 12-hour in vivo tin-retention study. In the Live/Dead study, the new
      stannous fluoride/sodium hexametaphosphate dentifrice killed approximately 90% to
      99% of the salivary microbes 16 hours after a single exposure. Similarly, the
      stannous fluoride dentifrice produced statistically significant reductions in
      plaque acid production and plaque regrowth activity compared to plaque treated
      with a standard fluoride dentifrice at all time intervals measured after product
      exposure (15 and 45 minutes). Results from the final two studies collectively
      demonstrated the presence of total soluble tin, which serves as a marker for the
      active stannous fluoride, at levels above the minimum concentration for
      inhibition of salivary bacteria metabolic activity 12 hours posttreatment. These
      findings confirm the long-lasting antibacterial action of the new stannous
      fluoride dentifrice, which serves as a basis for its therapeutic benefits.

PMID- 16999007
TI  - Anticalculus efficacy and safety of a stabilized stannous fluoride/sodium
      hexametaphosphate dentifrice.
AB  - The purpose of this study was to assess the anticalculus efficacy and long-term
      safety of a new stannous fluoride dentifrice containing sodium hexametaphosphate.
      This trial was a randomized, double-blind, parallel-group, 6-month study where,
      after a prophylaxis, subjects brushed twice daily with either a stabilized 0.454%
      stannous fluoride/13% sodium hexametaphosphate dentifrice (Crest Pro-Health) or a
      marketed multibenefit triclosan/copolymer control dentifrice. Study subjects were
      known to form supragingival calculus and had previously demonstrated the ability
      to form at least 1.5 mm using the Volpe-Manhold Calculus Index over a 2-month
      pretest period. Comparisons between treatments for anticalculus efficacy were
      performed using analysis of covariance. Eighty subjects were randomized into one
      of two treatment groups after stratification on gender and baseline calculus
      scores and then monitored for calculus formation, soft tissue tolerance, and
      extrinsic stain. The mean calculus score for the stannous fluoride/sodium
      hexametaphosphate group was statistically significantly lower than that of the
      triclosan/copolymer group at both months 3 and 6 (P < .01). At month 3, the
      stannous fluoride/sodium hexametaphosphate group had an adjusted mean 54% lower
      than that of the triclosan/copolymer group. At month 6, the stannous
      fluoride/sodium hexametaphosphate group had an adjusted mean 56% lower than that
      of the triclosan/copolymer group. Both dentifrices were well tolerated and
      neither dentifrice group developed appreciable extrinsic stain over the 6-month
      trial period. Overall, the stannous fluoride/sodium hexametaphosphate dentifrice
      had superior anticalculus efficacy relative to the marketed triclosan/copolymer
      control and a comparable soft tissue safety and extrinsic stain profile.

PMID- 16999008
TI  - Desensitizing effect of a stabilized stannous fluoride/Sodium hexametaphosphate
      dentifrice.
AB  - Stannous fluoride (0.4%) has been incorporated into oral hygiene products to
      reduce dentinal hypersensitivity since the 1960s. The present study was designed
      to assess the desensitizing efficacy of a stabilized 0.454% stannous
      fluoride/sodium hexametaphosphate dentifrice compared to a sodium fluoride
      control dentifrice. This was a double-blind, parallel-group, randomized clinical
      trial conducted according to the American Dental Association Guidelines for the
      Acceptance of Products for the Treatment of Dentinal Hypersensitivity. Seventy
      seven subjects who met the entrance criteria were stratified based on age,
      gender, and air-sensitivity scores and randomly assigned to either the stabilized
      stannous fluoride/sodium hexametaphosphate dentifrice or the sodium fluoride
      control dentifrice. Subjects were instructed to brush twice daily for 8 weeks.
      Oral soft tissue examination and efficacy assessments including tactile (Yeaple
      probe) and thermal (Schiff Air Index) sensitivity were made at baseline, week 4,
      and week 8. The mean sensitivity score based on the Schiff Air Index for the
      experimental group was statistically significantly lower than that of the sodium
      fluoride control group, at both weeks 4 and 8 (P < .0001). The mean sensitivity
      score based on the Yeaple Probe Index for the stannous fluoride/sodium
      hexametaphosphate group was statistically significantly higher, indicating a
      reduction in sensitivity, than that of the sodium fluoride control group, at both
      weeks 4 and 8 (P < .0001). The results demonstrate that the stabilized stannous
      fluoride/sodium hexametaphosphate dentifrice provides clinically and
      statistically significant reductions in dentinal hypersensitivity when compared
      to the sodium fluoride control dentifrice.

PMID- 16999009
TI  - Anticaries potential of a stabilized stannous fluoride/sodium hexametaphosphate
      dentifrice.
AB  - The objective of this research was to evaluate the anticaries potential of
      stabilized stannous fluoride and sodium hexametaphosphate dentifrice using a
      series of laboratory studies. In a study of fluoride uptake into demineralized
      enamel, the stannous fluoride/sodium hexametaphosphate dentifrice exhibited
      fluoride uptake comparable to the clinically proven stannous fluoride and silica
      dentifrice. Under lesion progression pH-cycling conditions, the stabilized
      stannous fluoride/sodium hexametaphosphate dentifrice was shown to protect teeth
      against lesion initiation and progression almost completely, and was comparable
      to conventional, clinically proven dentifrices. This series of well-controlled
      and validated in vitro studies demonstrates the anticaries potential of the
      stabilized stannous fluoride/sodium hexametaphosphate dentifrice. These in vitro
      results suggest that the stabilized stannous fluoride/sodium hexametaphosphate
      dentifrice may provide enhanced anticaries performance relative to a sodium
      fluoride control dentifrice. These results are reflective of the clinical
      benefits previously reported for stabilized stannous fluoride/sodium
      hexametaphosphate dentifrices.

PMID- 16999011
TI  - On-site health care: a launching pad for DM initiatives?

PMID- 16999010
TI  - Extrinsic whitening effects of sodium hexametaphosphate--a review including a
      dentifrice with stabilized stannous fluoride.
AB  - The number of tooth whitening products available to patients has grown
      dramatically during recent years. While peroxide is the primary agent found in
      products that bleach and remove intrinsic sources of discoloration, various
      ingredients are incorporated in formulations to remove and inhibit extrinsic
      sources of tooth discoloration, ie, tooth stain. Recently, an advanced antitartar
      ingredient with extrinsic-stain-inhibiting benefits was introduced: sodium
      hexametaphosphate. This long-chain condensed phosphate, also known as
      polypyrophosphate, chemically removes existing stains and provides long-lasting
      inhibition of new-stain chromogen adsorption. Sodium hexametaphosphate was
      originally introduced in a sodium fluoride dentifrice formulation and was later
      marketed in a chewing gum delivery system. Recently, sodium hexametaphosphate was
      launched in another dentifrice formulation containing stabilized stannous
      fluoride (Crest Pro-Health). This article reviews published clinical and
      laboratory data demonstrating sodium hexametaphosphate's extrinsic whitening
      benefits in all three formulations.

PMID- 16999012
TI  - New diabetes DM program targets high-risk seniors with high-intensity
      intervention.
AB  - Alere Medical has teamed up with Joslin Diabetes Centers to create a diabetes
      program that developers believe includes the 'best of everything' DM has to offer
      today. The approach is now being piloted in a group of high-risk senior patients
      at Health Net of Arizona with the hope that it can soon be expanded to many more
      patients and populations.

PMID- 16999013
TI  - Hospital systems nurture employer relationships with new emphasis on prevention.
AB  - A Nashville, TN-based company is helping hospitals attract employers with
      predictive modeling and customized roadmaps aimed at reducing health care costs.
      Figuring strongly in the effort are wellness initiatives and DM-style approaches
      to management and prevention.

PMID- 16999014
TI  - Can reduced co-pays boost outcomes, lower costs in diabetic patients?
AB  - Maybe not immediately, but investigators at the University of Michigan think the
      long-term answer may well be "yes." And what's more, there may even be a positive
      impact on overall medical costs. Definitive answers should be forthcoming soon as
      a just-lanched pilot study will be examining both of these issues over the next
      two years.

PMID- 16999015
TI  - [New features in the recommendations of the Second Hungarian Therapeutic
      Consensus Conference].
AB  - The First Hungarian Therapeutic Consensus Conference took place on 3rd Nov. 2003
      with the participation of 9 medical societies. Over the past 2 years the results
      of new major studies have been published and the American ATP III has also
      updated its guidelines issued in 2004. Based on the above proposals, the Second
      Hungarian Therapeutic Consensus Conference held on 3rd Nov. 2005 partly confirmed
      its earlier suggestions, but made some changes as well. Within the high risk
      category the Conference optionally created a very high risk group from those
      patients who - in addition to their cardiovascular disease--have either diabetes
      or metabolic syndrome or acut coronaria syndrome or who are chain smokers. We
      have included - as a complement - into the asymptomatic high risk category such
      newly emerging risk factors, one of which already in itself means high risk:
      ankle/arm index < or = 0.9, GFR <60 ml/min, microalbuminuria (30-300 mg),
      preclinical atherosclerosis (plaque). Besides, 4 other risk factors were also
      categorised such as Lp/a (> or = 30 mg/dl), CRP (> or = 3mg/l), homocysteine (>
      or = 12 micromol), familiarity--atherogenic gene constellation, but only the
      presence of at least two of these verify high risk. In very high risk group the
      goals of 3.5 mmol/l and 1.8 mmol/l were determined as therapeutic option. The
      goal in obese patients--expressed earlier only in BMI--can now be equally
      determined by the abdominal circumference (94 cm for men, 80 cm for women
      respectively). ACE inhibitors were recommended earlier as a preventive therapy in
      case of dysfunction of the left ventricle, while at present they are suggested
      for all patients with cardiovascular disease. In the recent recommendations
      guidelines related to nutrition, smoking, exercise have also been included.

PMID- 16999016
TI  - [Hyperthyroidism].
AB  - Although the classical presentation of hyperthyroidism is known from the
      nineteenth century, the mindful evaluation of the clinical symptoms is
      indispensable for the practitioner physician. The clinical picture depends on the
      etiology of hyperthyroidism, the gender and age of the patient. The methods for
      the laboratory diagnosis of hyperthyroidism have outstanding accuracy, the
      supersensitive TSH, free thyroxine and triiodothyronine determinations are
      generally available. The etiology of hyperthyroidism was broadened by new
      diseases: gestational hyperthyroidism caused by human choriogonadotropin and the
      group of congenital non-autoimmune hyperthyroidism due to TSH receptor mutations
      were discovered. The iodine-induced hyperthyroidism, which is an everyday problem
      due to the widespread use of amiodarone treatment, is also better characterized.
      The role of different treatment modalities in the therapeutic algorithm was
      established, the part of surgery decreased. The optimal duration and dose of drug
      treatment in Graves' disease is still questionable in the lack of good evidence,
      nowadays one and half year of antithyroid treatment is generally recommended. The
      reduction of relapse rate below 50% after the discontinuation of antithyroid drug
      was unsuccessful, risk factors are the large goiter, elevated level of the TSH
      receptor antibodies, in certain studies the male gender and young age. Due to the
      high relapse rate, the radioiodine treatment is preferred, even as a primary
      therapy. In case of toxic adenoma, toxic multinodular goiter and congenital non
      autoimmune hyperthyroidism the medical treatment cannot result in permanent cure,
      therefore primary ablative treatment is required. The chances of patients with
      hyperthyroidism for the complete recovery are excellent, however, long time
      follow-up is necessary.

PMID- 16999017
TI  - [Radiochemotherapy of cervical carcinoma. (Necessity of dose reduction in
      chemotherapy)].
AB  - INTRODUCTION: The concurrent radiochemotherapy used in the treatment of high risk
      and locally advanced cervical cancer therapy seems to be standard practice.
      Studies carried out in 1999 and 2000, reported the results of five large-scale
      prospective randomized investigations using radiotherapy which showed progression
      free and overall survival rate increase compared to use of solely radiotherapy
      (Gynecology Oncology Group (GOG) 123, South West Oncology Group (SWOG) 8797,
      Radiotherapy Oncology Group (RTOG) 9001, Gynecology Oncology Group (GOG) 85,
      Gynecology Oncology Group (GOG) 120). OBJECTIVES: The aim of the investigation
      was to report our early findings of cervical cancer radiotherapy detailing the
      arising radiogen toxicity. METHOD: This is a report of a study carried out at the
      Oncoradiology Centre of Budapest, (between July 2002 and March 2005) on 66
      cervical cancer patients. In concurrent radiotherapy the total dose of high
      photon energy percutaneous radiotherapy (megavolt therapy) for the pelvic region
      was 50.4 Gy, in 1.8 Gy fractions and with the weekly dosage of 40 mg/m2 cisplatin
      prior to the radiotherapy. RESULTS: The planned cytostatic treatment could be
      carried out on 27 patients (41%) on five treatments. At the same time, the number
      of treatments on the other patients had to be reduced due to haematological
      toxicity in the following way: 4 treatments on 16 patients (24%), 3 treatments on
      7 patients (11%), 2 treatments on 10 patients (15%) and once on 6 patients (9%).
      Altogether it was necessary to reduce the dosage from the planned protocol, on 44
      patients (67%). The optimal radiotherapy time of 56 days as reported in the
      literature, was exceeded in 17 cases (26%) on account of the radiogen toxicity.
      CONCLUSIONS: On the basis of our own results it is not advisable to raise the
      cisplatin weekly dosage to above 20 mg/m2.

PMID- 16999018
TI  - [Anatomic correction of the congenitally corrected transposition of the great
      vessels by the first successful "double switch" operation in Hungary].
AB  - Congenitally corrected transposition of the great arteries is a rare defect
      characterized by discordant atrioventricular and ventriculoarterial connections.
      Symptoms result from one or a combination of associated cardiovascular
      malformations, including ventricular septal defect, pulmonary stenosis or
      atresia, tricuspid valve dysfunction, dextrocardia, hypoplastic left or right
      ventricle. Correcting exclusively the associated defects, leaving the morphologic
      right ventricle in systemic position, will determine the patient's life-long
      prognosis. Anatomic repair by double switch technique may improve survival of
      patients with congenitally corrected transposition of the great arteries by
      establishing the morphologic left ventricle in the systemic circulation. A 3-year
      old girl with congenitally corrected transposition of the great arteries,
      ventricular septal defect, hypoplastic right ventricle, and previous palliative
      procedure was corrected by double switch technique and patch closure of
      ventricular septal defect. The authors prefer the double switch procedure inspite
      of its many surgical challenges because it has very good long-term outcome. The
      more simple surgery namely the operation of only associated cardiac defects will
      involve the possibility of deterioration of right ventricular function.

PMID- 16999019
TI  - [Professor Ferenc Farago--his life and tragedy].

PMID- 16999020
TI  - [Peptic ulcer].

PMID- 16999021
TI  - [Renal cell cancer].

PMID- 16999022
TI  - Genetic basis of HIV-1 resistance and susceptibility: an approach to understand
      correlation between human genes and HIV-1 infection.
AB  - HIV infection is the serious medical and public health issue of present
      generation. By 2005, it has already infected a cumulative total of more than
      sixty million people worldwide and the number of HIV positive cases are rising
      day by day. India is currently estimated to have about 5.1 million infected
      persons with HIV-1 or AIDS (second only to South Africa) and this number could
      increase to 24 million in the next ten years. This pandemic situation of the AIDS
      stimulated a plethora of longitudinal cohort studies which are designed to
      document medical heterogeneity as well as to mitigate the factors that regulate
      the HIV-1 infection, disease progression and the immune defenses. In recent years
      these genetic studies have led to the discovery of various MHC and non MHC
      encoded genes, which directly or indirectly influence the susceptibility and
      resistance to HIV infection and AIDS. These genes and their mutated forms and
      their products which play a major role in determining the susceptibility or
      resistance to HIV-1 infection and AIDS. These genes have been categorized into
      MHC or non MHC encoded genes. The MHC encoded genes which determine HIV
      resistance or susceptibility are HLA-B57, HLA-B58, HLA-B27, HLA-Bw4 and HLA-A11
      in Southeast Asians. On the other hand, non MHC encoded genes are CCR5, CCR2,
      RANTES, CXCL12, CXCR6, CCL3L1, Interleukin-10 (IL-10), and interferon gamma. The
      site specific mutations in these genes determine the susceptibility or resistance
      to HIV-1 infection and AIDS. In future the study of host genes in relation to HIV
      1 infection may provide the researchers to develop newer chemotherapeutic
      approaches to prevent or cure HIV-1 infection effectively.

PMID- 16999023
TI  - Differential role of MAP kinase isoforms in malachite green transformed Syrian
      hamster embryo fibroblasts in culture.
AB  - Malachite green (MG) induces DNA damage and malignant transformation of Syrian
      hamster embryo (SHE) cells in primary culture. In the present study, we have
      studied the role of all the three isoforms of mitogen activated protein (MAP)
      kinases i.e. ERK (extracellular regulated kinase), JNK (JUN- N- terminal kinase)
      and p38 kinase during transformation of SHE cells by MG. The results showed that
      transformed cells were associated with a decreased expression of phosphoactive
      ERK and JNK and increased expression of p38 kinase as evident from the Western
      blot, immunofluorescence and flow cytometry studies. Also, a persistent nuclear
      localization of p38 kinase was observed in the transformed cells. The present
      study indicated that p38 kinase was present at higher levels and seemed to be
      associated with transformation, which suggested that inhibitors of p38 kinase
      could serve in general as potential agents for selective cancer therapy.

PMID- 16999024
TI  - Neuroprotective effect of BDNF in young and aged 6-OHDA treated rat model of
      Parkinson disease.
AB  - Brain derived neurotrophic factor (BDNF) has been shown to exert trophic effects
      on dopaminergic neurons against 6-hydroxydopamine (6-OHDA) in young rat. Since
      the degeneration of substantia nigra dopaminergic neurons that occurs in
      Parkinson's disease is more often than not confined to elderly individuals, it is
      of interest to determine whether the effects of BDNF against 6 hydroxydopamine (6
      OHDA) in young rats can be extended to aged animals. 6-hydroxydopamine was
      stereotaxically injected into the striatum of young (3-months) and aged (24
      months) rats, which were treated two hours earlier with BDNF. 6-OHDA results in
      almost complete destruction of substantia nigra pars compacta dopaminergic
      neurons. BDNF injection significantly changed apomorphine induced rotations from
      132 +/- 15 to 181 +/- 10, staircase test from 73 +/- 2% to 61 +/- 3%, initiation
      time from 7 +/- 2 to 12 +/- 1 sec, and disengage time from 80 +/- 7 to 90 +/- 5
      sec in young and aged animals, respectively. It is concluded that BDNF causes the
      limited behavior recovery of striatal DA systems from 6-OHDA toxicity in aged
      animals.

PMID- 16999025
TI  - Long term excessive Zn-supplementation promotes metabolic syndrome-X in Wistar
      rats fed sucrose and fat rich semisynthetic diet.
AB  - During the last two decades Zinc (Zn) as a micronutrient is being used
      indiscriminately in agricultural and husbandry practices and also in baby foods
      and multivitamin supplements with a view that Zn is non-toxic and promotes linear
      growth and body weight in the consumers. The long-term effect of increasing Zn
      load in the body has not been worked out so far. In this study, three groups of
      rats were fed on a semi-synthetic diet containing 20 mg (control, group-I), 40 mg
      (group-II) and 80 mg Zn /kg (group-III) diet respectively for 6 months. The
      results revealed that the gain in body weight increased in rats in Zn
      concentration dependent manner. The urine examined on weekly basis showed
      glucosuria in group-II on week 10 and in group-III on week 8 and thereafter. The
      arterial blood pressure was significantly higher in group-II and III than their
      control counter parts on monthly basis. Histochemical examination of skin
      revealed an increase in the number of adipocytes filled with triglycerides making
      a subcutaneous fatty tissue thicker in group-II and group-III than that of
      control group. The blood profile after 180 days of dietary treatment, displayed a
      significant rise in glucose, total lipids, cholesterol, triglycerides, LDL
      cholesterol, VLDL-cholesterol, insulin, cortisol and aldosterone whereas HDL
      cholesterol, T3, T4 and TSH showed a reduction in their levels in the blood
      serum. The tissue metal status showed an increase of Zn, Cu and Mg in the serum,
      a rise in Zn in liver, hair and abdominal muscles and fall in Cu and Mg
      concentrations in liver, hair and abdominal muscles. This data suggest that Zn in
      excess in diet when fed for longer periods of time induces metabolic syndrome-X.

PMID- 16999026
TI  - Effect of AC II, a herbal formulation on radiation-induced immunosuppression in
      mice.
AB  - A single dose of 6 Gy irradiation significantly reduced the total WBC count while
      in herbal formulation (AC II) treated groups it was found to be significantly
      increased. Similarly bone marrow cellularity and alpha-esterase positive cells,
      which were lowered by radiation, were partly restored in AC II treated groups.
      The data indicate that AC II can overcome the immunosuppression produced by
      irradiation.

PMID- 16999027
TI  - Immunostimulatory effect of Tinospora cordifolia Miers leaf extract in
      Oreochromis mossambicus.
AB  - Immunostimulatory effect of leaf extract of T. cordifolia on (i) specific
      immunity (antibody response), (ii) non-specific immunity (neutrophil activity)
      and (iii) disease resistance against Aeromonas hydrophila was investigated in O.
      mossambicus. Ethanol and petroleum ether extracts of the leaves were used. Both
      ethanol and petroleum ether extracts administered at doses of 0.8, 8 or 80 mg/kg
      body weight, prolonged the peak primary antibody titres upto one to three weeks.
      Ethanol extract at the dose of 8 mg/kg and petroleum ether extract at the doses
      of 0.8 or 8 mg/kg enhanced the secondary antibody response. All the doses of
      ethanol extract significantly enhanced neutrophil activity. Fish injected with
      petroleum ether or ethanol extract at a dose of 8 mg/kg were protected against
      experimental infection with virulent A. hydrophila. The results indicates the
      potential of T. cordifolia leaf extracts for use as an immunoprophylactic to
      prevent diseases in finfish aquaculture.

PMID- 16999028
TI  - Cumulative antioxidant defense against oxidative challenge in galactose-induced
      cataractogenesis in Wistar rats.
AB  - Natural dietary ingredients are known for their antioxidant activity. Of such,
      curcumin, the active principle of turmeric, at 0.01% in the diet proved as pro
      oxidative in galactose-induced cataract in vivo. The purpose of this study was to
      investigate the effect of vitamin E (VE), a well-known antioxidant, in
      combination with curcumin on the onset and maturation of galactose induced
      cataract. Periodic slit-lamp microscope examination indicated that in combination
      with vitamin-E, 0.01% curcumin (G-IV) delayed the onset and maturation of
      galactose-induced cataract. Biochemical analyses revealed that combined treatment
      of 0.01% curcumin and vitamin-E diet exhibited an efficient antioxidant effect,
      as it inhibited lipid peroxidation and contributed to a distinct rise in reduced
      glutathione content. The results indicate that natural dietary ingredients are
      effective in combination rather than the individual administration as they are
      complementing each other in reducing the risk of galactose induced cataract.

PMID- 16999029
TI  - Evaluation of herbal coccidiostat 'Coxynil' in broiler.
AB  - Anticoccidial efficacy of "Coxynil" a polyherbal preparation was tested against
      Eimeria tenella in broilers. Body weight of birds challenged with E. tenella in
      Coxynil treated groups was higher as compared to Coxynil untreated. Oocyst out
      put, lesion score, HI titres against New Castle disease virus were significantly
      higher in Coxynil supplemented groups in comparison to Coxynil un-supplemented
      groups. Examination of ceaca of the birds, revealed that the Coxynil interfered
      with life cycle of coccidia. The typical second generation schizonts were absent
      in ceacal section of Coxynil treated groups. The results indicate that Coxynil is
      effective herbal coccidiostat.

PMID- 16999030
TI  - Biochemical effects of Nigella sativa L seeds in diabetic rats.
AB  - Oral administration of ethanol extract of N. sativa seeds (300 mg/kg body
      weight/day) to streptozotocin induced diabetic rats for 30 days significantly
      reduced the elevated levels of blood glucose, lipids, plasma insulin and improved
      altered levels of lipid peroxidation products (TBARS and hydroperoxides) and
      antioxidant enzymes like catalase, superoxide dismutase, reduced glutathione and
      glutathione peroxidase in liver and kidney. The results confirm the antidiabetic
      activity of N. sativa seeds extract and suggest that because of its antioxidant
      effects its administration may be useful in controlling the diabetic
      complications in experimental diabetic rats.

PMID- 16999031
TI  - Prepatent detection of Fasciola gigantica infection in bovine calves using
      metacercarial antigen.
AB  - Metacercarial antigen of Fasciola gigantica was evaluated for early
      immunodiagnosis of experimental bovine fasciolosis using ELISA and Western blot.
      In ELISA, the experimental F. gigantica infection was detected as early as 2
      weeks post-infection (WPI). The gradual increasing trend of antibody level was
      observed from 2 to 7 WPI, followed by a plateau, which was maintained up to 14
      WPI. In Western blot, sera from experimentally infected calves recognized one
      distinct polypeptide of 21 kDa in fractionated metacercarial antigen as early as
      10th day post infection. From 2 WPI, more polypeptide bands were reacting.
      Recognition of these protein bands persisted till the end of the experiment (14
      WPI). Cattle sera collected from the field showed 34.5% seroprevalence of
      fasciolosis by ELISA using MAg. Comparative immunoblot studies of metacercarial
      antigen with anti-Gigantocotyle explanatum and anti-Paramphistomum epiclitum sera
      revealed that 21 and 25 kDa polypeptides of metacercarial antigen did not cross
      react with any of these sera and appear to be unique to F. gigantica and having
      the desirable qualities of early and specific immunodiagnosis.

PMID- 16999032
TI  - Bioactivity of marine organisms: part X--screening of some marine fauna from the
      Indian coasts.
AB  - Methanolic and chloroform-methanol extracts of 25 identified species of marine
      fauna have been screened for a wide range of biological activities. Of these, 2
      extracts exhibited diuretic activity, while antibacterial, antiviral, oxytocic
      and spasmolytic activities, were observed in 1 extract each.

PMID- 16999033
TI  - Efficient protocols for in vitro regeneration of Pennisetum glaucum (L) Br.
AB  - A system was developed for in vitro regeneration of Pennisetum glaucum through
      organogenesis and somatic embryogenesis. Mature embryo and leaf base explants of
      Pennisetum glaucum (L) Br. cv HH B60 (Poaceae) were cultured on Murashige and
      Skoog agar medium supplemented with 11.3 microM of 2,4-D for callus induction.
      Embryogenic calli were induced within eight weeks. Percentage of callus induction
      and somatic embryogenesis was significantly higher in mature embryo than leaf
      base explants. Maximum shoot regeneration was obtained via organogenesis on MS
      medium supplemented with 4.43 microM of BAP and 4.64 microM of kinetin from the
      calli of both the explants. The frequency of plant regeneration through somatic
      embryogenesis was comparatively lower than organogenesis. Regeneration frequency
      was higher in mature embryo explants than leaf base explants. The shoots
      regenerated via organogenesis were elongated and rooted efficiently on MS medium
      supplemented with IBA (0.49 microM). The rooted plantlets were hardened and
      transferred to soil.

PMID- 16999034
TI  - In vitro propagation of threatened terrestrial orchid, Malaxis khasiana Soland
      ex. Swartz through immature seed culture.
AB  - Rapid in vitro propagation of the terrestrial orchid, M. khasiana through
      immature seed culture was achieved. Immature seeds of 8-9 week after pollination
      (WAP) cultured on MS medium (2% sucrose) supplemented with 500 mgl(-1) casein
      hydrolysate and 1 microM N6-benzyladenine (BA) exhibited germination of 75% seeds
      after 107 days of culture and subsequently supported the development of PLBs.
      Subsequent culture on MS medium enriched with 6 microM of indole-3-acetic acid
      (IAA), 18 microM each of BA and kinetin induced multiple shoots and plantlets.
      Transfer of PLBs to MS medium with 0.1% activated charcoal (AC) facilitated rapid
      proliferation of PLBs, while AC at 0.2% favored shoot bud induction and rhizome
      enlargement. The plantlets, developed on medium with IAA, BA and kinetin, after
      hardening in vitro for 8-10 weeks were planted in community pots and transferred
      to poly-house. The plantlets showed 65% survival under field conditions.

PMID- 16999035
TI  - Catalytic and regulatory properties of sulphur metabolizing enzymes in
      cyanobacterium Synechococcus elongatus PCC 7942.
AB  - Synechococcus elongatus PCC 7942 was able to grow with several S sources. The
      sulphur metabolizing enzymes viz. ATP sulphurylase, cysteine synthase,
      thiosulphate reductase and L- and D-cysteine desulphydrases were regulated by
      sulphur sources, particularly by sulphur amino acids and organic sulphate esters.
      Sulphur starvation reduced ATP sulphurylase and cysteine synthase whereas reduced
      glutathione appreciated Cys degradation activity. With partially purified enzymes
      apparent Km values for sulphate, ATP, D- and L-Cys, thiosulphate, sulphide and O
      acetyl serine were in a range of 12-50 microM. p-Nitrophenyl sulphate inhibited
      ATP sulphurylase competitively. Met was a feedback inhibitor of several key
      enzymes.

PMID- 16999036
TI  - [Parasitic dead-end: update].
AB  - Parasitic dead-ends occur when a parasite is unable to establish a permanent
      interaction in an unnatural host. Although the likelihood of successful
      reproduction by the pathogenic agent is nul, parasitic dead-end heralds capture
      of new parasites and therefore expansion of the host range. Angiostrongyliasis
      due to A. cantonensis or A. costaricensis, anisakiasis, Ancylostoma caninum
      infection, gnathostomiasis and sparganosis are undoubtedly emerging zoonoses of
      particular medical interest. Prevention of these diseases relies on abstinence
      from eating raw meat from invertebrates or cold-blooded (poikilotherm)
      vertebrates (e.g. used in exotic dishes). These guidelines must be included in
      recommendations to travelers.

PMID- 16999037
TI  - [Therapeutic alternatives in case of failure of first-line treatment of
      intestinal helminthiasis in adults].
AB  - Development of antiparasite medications over the last 15 years has greatly
      reduced the number of treatment failures for intestinal helminthiasis.
      Benzimidazole derivatives, ivermectine, praziquantel and triclabendazole are easy
      to use, well tolerated and generally curative. First-line treatment are currently
      so reliable that failure should lead first to investigation of possible "false
      failure" causes such as misdiagnosis, poor identification of the parasite,
      inadequate or incorrect treatment, and repeat contamination, before concluding
      that genuine parasite resistance is involved and that alternative therapy is
      needed. Nitazoxanide is an alternative treatment for fascioliasis and teniasis.
      Albendazole can be beneficial for taeniasis and strongyloidiasis. Metronidazole
      can be effective for fascioliasis. Artemisinine derivatives are useful for
      schistosomiasis. Combined therapies are necessary for refractory ankylostomiasis.

PMID- 16999038
TI  - [Development of novel antihelminthic therapies].
AB  - Since existing medications are effective, easy-to-use and well tolerated,
      research in the treatment of helminthiasis in humans seems to be at a standstill.
      However this type of parasitic infection is still a major public-health concern
      and heavy socioeconomic burden in many countries. Despite observance of the first
      disturbing signs of resistance, release of new antihelminthics on the market
      (e.g. nitazoxanide and tribendimidine) remains slow. Treatment using drug
      combinations offers an alternative for therapeutic failure in some cases. Ongoing
      studies focusing on development of a vaccine, on adaptation of medications used
      in veterinary medicine or on the action of medicinal plants hold forth hope of
      finding effective new treatments.

PMID- 16999039
TI  - [Filariasis control: entry point for other helminthiasis control programs?].
AB  - Filariasis control programs are based on a decentralized drug distribution
      strategy known as "community-directed". This strategy could also be applied to
      the control of schistosomiasis and intestinal nematode infections. Integration of
      these control programs could be highly cost-effective. However, as a prerequisite
      for integration, it would be necessary to identify zones where these helminthic
      infections co-exist, specify the population categories that should receive each
      medication (ivermectin, albendazole, mebendazole, and praziquantel), check that
      combined administration of these drugs is safe and ensure that an integrated
      program would have no detrimental effect on the health care system and on the
      efficacy of ongoing programs.

PMID- 16999040
TI  - [National research center for AIDS and viral hepatitis: a novel and dynamic
      research facility].

PMID- 16999041
TI  - [Nutritional problems associated with human retrovirus infection in tropical
      zones and possible response strategies].

PMID- 16999042
TI  - [Severe opportunistic infections in HIV-positive adults in sub-Saharan Africa].
AB  - The threat for opportunistic diseases in HIV-infected adults in sub-Saharan
      Africa is characterized by a higher frequency of tuberculosis and invasive
      bacterial diseases than in Europe and by the presence of malaria. Since these
      three infections may occur early after the onset of immuno-deficiency, HIV
      infected patients with less than 200 CD4/mm3 are more likely to develop an
      infectious episode with severe morbidity in sub-Saharan Africa than in Europe.
      For this reason the WHO now recommends starting cotrimoxazole prophylaxis at 350
      and even 500 CD4/mml in sub-Saharan Africa. The question of whether
      antiretroviral treatment should also be initiated "earlier" in sub-Saharan Africa
      than in Europe has also been raised.

PMID- 16999043
TI  - [The French Red Cross: a network of care centers dedicated to HIV-AIDS].
AB  - The commitment of the French Red Cross Society to the fight against HIV/AIDS in
      Africa and Asia is based on day care centers (DCC) set up and operated within
      public hospitals. These outpatient facilities offer global care including
      clinical and biologic follow-up for patients undergoing anti-retroviral
      treatment. In most countries these DCC have become reference centers providing
      support for national decentralization policies. To reinforce the impact of their
      activities, centers offer regular educational programs and provide extensive
      training for medical personnel.

PMID- 16999044
TI  - [French sanitary cooperation in developing countries].
AB  - In the face of a worsening public health situation throughout the world, French
      know-how in the field of sanitary cooperation warrants a far more active
      commitment from our country. Instead there have been only a few initiatives and
      we are witnessing a programmed decline of our presence. The statement issued by
      the Economic and Social Council in 2006--the highlights of which will be
      presented at this meeting--strongly advocates a voluntary program to revive
      sanitary cooperation by encouraging civic-spirited young people to express
      international solidarity through public service in impoverished areas. By
      compensating the shortage of human resources in developing countries, this
      program would allow immediate implementation of measures to promote action,
      training and research not as a replacement operation but rather as a genuine
      partnership. Deployment of our public aid for development in the field of health
      care must not have a detrimental effect on the bilateral dimension of the
      relationship that indeed requires urgent strengthening. In addition tighter
      coordination of all parties involved in cooperation activities is needed to
      ensure greater efficiency and consistency. New funding sources (starting with the
      airline ticket tax) and greater mobilization of the European Union is necessary
      to ensure that developing countries have more financial resources to wage the
      "health-care battle". Reducing the "health-care gap" that cripples development
      and destabilizes societies must be the first priority of French Cooperation.

PMID- 16999045
TI  - Certificate Program for Otolaryngology Personnel (CPOP): A good solution for many
      practice challenges.

PMID- 16999046
TI  - Aberrant facial nerve.

PMID- 16999047
TI  - An unusually large choanal polyp that almost completely obstructed the
      oropharyngeal airway.

PMID- 16999048
TI  - Bilateral vocal fold polyps.

PMID- 16999049
TI  - Neoplasms metastatic to the thyroid gland.

PMID- 16999050
TI  - The submucosal fish bone.

PMID- 16999051
TI  - The 'normal' audiogram.

PMID- 16999052
TI  - Double swallow.

PMID- 16999053
TI  - Outpatient management of infected hardware in the oncology patient.

PMID- 16999054
TI  - Appeal theft.

PMID- 16999055
TI  - Long-term follow-up after gentamicin application via the Silverstein MicroWick in
      the treatment of Meniere's disease.
AB  - We conducted a retrospective study to evaluate the long-term effectiveness of
      gentamicin applied directly to the round window membrane via the Silverstein
      MicroWick system in patients with definite or probable Meniere's disease. The
      study population was made up of 69 patients who had received 3 drops of
      gentamicin 10 mg/ml three times daily; the duration of treatment was guided by
      objective data obtained from weekly electronystagmography and audiometry. Relief
      of vertigo was assessed by chart review and telephone interviews. After a minimum
      follow-up of 24 months, we found that vertiginous symptoms remained controlled in
      53 patients (76.8%) after one or more courses of drug therapy. A single course of
      treatmentwas successful in 41 patients (59.4%). We conclude that long-term
      control of vertigo can be achieved inpatients with Menere's disease by direct
      application of gentamicin to the round window membrane via the Silverstein
      MicroWick. This minimally invasive self-treatment technique was well tolerated
      and free of long-term complications.

PMID- 16999056
TI  - Pharmacokinetically enhanced amoxicillin/clavulanate (2,000/125 mg) in acute
      bacterial rhinosinusitis caused by Streptococcus pneumoniae, including penicillin
      resistant strains.
AB  - We evaluated the efficacy of a new pharmacokinetically enhanced formulation of
      amoxicillin/clavulanate (2,000/125 mg) twice daily for the treatment of acute
      bacterial rhinosinusitis (ABRS) caused by Streptococcus pneumoniae, particularly
      penicillin-resistant S pneumoniae (PRSP; penicillin minimum inhibitory
      concentrations [MICs]: > or = 2 microg/ml. A total of 2,482 patients received
      study medication (safety population). Of these, 2,324 were clinically evaluable
      (efficacy population), and 1,156 of them had at least one pathogen isolated at
      screening (bacteriology population). S pneumoniae was isolated from 371 patients
      in the bacteriology population, including 37 with PRSP. Follow-up in the
      bacteriology population on days 17 through 28 revealed that
      amoxicillin/clavulanate therapy was successful in 345 of 371 patients with S
      pneumoniae infection (93.0%) and in 36 of 37patients with PRSP infection (97.3%),
      including 7 of 8 patients (87.5%) whose amoxicillin/clavulanic acid MICs were 4/2
      microg/ml or higher. Pharmacokinetically enhanced amoxicillin/clavulanate was
      generally well tolerated, as only 2.2% of patients withdrew because of adverse
      events. This agent represents a valuable new therapeutic option for the empiric
      treatment of ABRS, particularly in areas where antimicrobial-resistant pathogens
      (including beta-lactamase-positive organisms) are prevalent, and for the
      treatment of patients who are at increased risk of infection with PRSP.

PMID- 16999057
TI  - Associations between fatigue and medication use in chronic rhinosinusitis.
AB  - We conducted a prospective study of 586 adults to determine if associations exist
      between fatigue symptom scores and three classes of medications prescribed for
      the treatment of chronic rhinosinusitis (CRS): prescription nonsedating
      antihistamines, topical nasal steroids, and antibiotics. Patients were assessed
      with the assistance of the Rhinosinusitis Symptom Inventory and Likert-scale
      fatigue symptom scores. On multivariate analysis and correcting or disease
      severity, we found that significantly higher fatigue symptom scores were
      associated with the use of nonsedating antihistamines (mean Likert score: 2.75
      vs. 2.27 for patients not taking a nonsedating antihistamine; p = 0.029). Higher
      fatigue scores were also associated with a greater number of antibiotic courses
      and more total weeks of antibiotic use (p < 0.001 in both cases). No association
      was seen between fatigue scores and the use of topical nasal steroids (mean
      Likert score: 2.65 vs. 2.24; p = 0.658). We recommend that long-term use of a
      nonsedating antihistamine be scrutinized in CRS patients who report symptoms of
      fatigue.

PMID- 16999058
TI  - Platelet-rich plasma in endoscopic sinus surgery.
AB  - The author designed a study to assess the healing properties of platelet-rich
      plasma (PRP) after endoscopic sinus surgery in 30 patients with bilateral and
      symmetrical chronic rhinosinusitis that was refractory to medical management. At
      the conclusion of each operation, PRP was introduced into the middle meatus of a
      randomly chosen side, while the other side was treated normally and served as a
      control. Patients were followed until both sides healed. After 13 operations,
      follow-up evaluations demonstrated no benefit to the use of PRP, and the study
      was terminated early. In general, both sides healed quickly and uneventfully as
      expected. There appears to be no advantage to the use of PRP in endoscopic sinus
      surgery.

PMID- 16999059
TI  - Office-based arytenoid palpation for diagnosis of disorders of bilateral vocal
      fold immobility.
AB  - Bilateral vocal fold immobility is an uncommon but serious condition with many
      causes. Accordingly, accurate diagnosis is essential in order to treat patients
      promptly and avoid long-term sequelae. Historically, diagnosis has been performed
      in the operating room with the patient under general anesthesia. We present the
      case of a patient who was diagnosed with bilateral vocal fold immobility by in
      office arytenoid palpation that required only topical anesthesia of the larynx.
      The patient subsequently underwent appropriate treatment. In our opinion, office
      based arytenoid palpation is a simple, safe, and accurate procedure for
      diagnosing bilateral vocal fold immobility.

PMID- 16999060
TI  - Free-text data entry by speech recognition software and its impact on clinical
      routine.
AB  - We conducted a study to evaluate speech recognition software in an
      otorhinolaryngology unit and to assess its impact on productivity prior to
      general implementation. Current speech recognition software (IBM ViaVoice,
      version 10) was implemented on a personal computer with a 2-GHz central
      processing unit, 256 MB of RAM, and a 30-GB hard disk drive, with and without add
      on professional vocabulary for otorhinolaryngology. This vocabulary was added by
      the automated analysis of an additional 12,257 documents from our department. We
      compared the word recognition error rates for three different text types and
      determined their impact on the amount of surgeon's time that was invested in the
      production of an error-free document. Although error rates without any
      professional vocabulary database were rather high (operation reports: 38.72%;
      consultation notes: 27.77%), the patient information was edited with a
      satisfactory result (10.65%). Best results were obtained with the specialty
      related vocabulary database added by the analysis of our own documents (operation
      reports: 5.45%; consultation notes: 5.21%). An increase in productivity compared
      with that of conventional transcription was found at an error rate of less than
      16%.

PMID- 16999061
TI  - Thyroidectomy for substernal goiter via a mediastinoscopic approach.
AB  - We report an unusual case in which a patient presented with a large posterior
      mediastinal goiter that extended to the level of the aorta. The goiter was
      resected through a standard Kocher neck incision with mediastinoscopic
      assistance. The large goiter was completely excised without the need for a
      sternotomy.

PMID- 16999062
TI  - Fibrin glue in thyroid and parathyroid surgery: is under-flap suction still
      necessary?
AB  - The introduction of fibrin sealants has brought into question the necessity of
      routinely placing suction drains. We conducted a retrospective study to determine
      whether fibrin sealants are comparable to traditional drains in terms of length
      of hospital stay and hematoma prevention. We evaluated 124 patients who had
      undergone thyroidectomy and 47 patients who had undergone parathyroidectomy. Of
      these, 22 thyroid surgery patients and 10 parathyroid surgery patients had their
      incisions closed without a drain after the application of fibrin glue. We found
      that the use of fibrin glue resulted in a statistically significant decrease in
      the length of hospital stay following both types of surgery (p = 0.033 and p =
      0.022, respectively). Two hematomas in the drain group required immediate
      surgical evacuation; in both of these patients, the suction was clotted and
      ineffective. One minor hematoma occurred in the fibrin glue group, and it was
      opened at the bedside 24 hours after surgery. We conclude that fibrin sealants
      offer a comparative advantage over under-flap suction in both thyroid and
      parathyroid surgery. Also, fibrin glue is less expensive, and its use obviates
      the discomfort felt by patients when a drain is removed.

PMID- 16999063
TI  - Primary carcinoid tumor of the parotid gland: A case report and review of the
      literature.
AB  - Salivary gland tumors account for 3 to 6% of all head and neck neoplasms in
      adults. Some 70 to 85% of these lesions are found in the parotid. Carcinoid
      tumors, which represent a distinct and relatively uncommon subset of
      neuroendocrine tumors, are most commonly found in the gastrointestinal tract,
      although in rare cases they are known to occur in extragastrointestinal
      locations, including the larynx, middle ear and pancreas. Malignancies of the
      parotid gland are uncommon (approximately 25% of parotid neoplasms), and to the
      best of our knowledge, a primary carcinoid tumor of the parotid has not been
      previously described in the literature. Reports of parotid carcinoid tumors
      during the past 30 years have described the presence of nonparotid primary
      carcinoid tumors (usually gastrointestinal) that had been diagnosed and treated
      several years prior to the presentation of the parotid lesion. Under such
      circumstances, the parotid lesion may be assumed to have been a metastatic rather
      than a primary carcinoid. This report documents what we believe is the first case
      of a primary carcinoid tumor of the parotid gland. We detail the clinical,
      surgical, radiologic, immunologic, and histochemical findings associated with its
      diagnosis, and we describe our management of this case. Although a primary
      carcinoid in this location is exquisitely rare, knowledge of such lesions is
      important because their management is substantially different from that of other
      parotid tumors. In particular, it is important to differentiate them from
      metastatic tumors from other sites.

PMID- 16999064
TI  - Spinal accessory nerve monitoring with clinical outcome measures.
AB  - We conducted a prospective study of 11 patients to (1) determine the feasibility
      of electrophysiologic monitoring of the spinal accessory nerve (SAN) during
      modified radical neck dissection, (2) determine whether a threshold increase in
      current is required to stimulate the SAN by comparing the amount of current on
      initial identification of the SAN and the amount of current after completion of
      the dissection prior to closure, and (3) determine whether clinical outcome
      measures of shoulder syndrome at 72 hours and 45 days postoperatively are
      affected by a threshold increase. We found that 3 of 11 patients (27.3%)
      experienced significant threshold increases (>0.4 mA) on completion of the
      dissection. Of 8 patients who completed a shoulder syndrome evaluation, 3 (37.5%)
      had scapular winging, mild to moderate pain, and less than 90% of shoulder
      abduction. Two of 3 patients with shoulder syndrome had a threshold increase on
      electrophysiologic monitoring. We conclude that electrophysiologic monitoring of
      the SAN is feasible. It did not identify a threshold increase in more than 70% of
      patients. Electrophysiologic integrity of the SAN did not completely correlate
      with clinical outcome measures for shoulder syndrome.

PMID- 16999065
TI  - [The ergonomic aspects of space vehicle manual motion control during re-entry].
AB  - In 1960s, the Russian space program spared no resources for extensive theoretical
      and empiric studies of manual control by vehicles during re-entry at the second
      and first space speeds by cosmonauts experiencing g-loads of up to 18 g. About
      6,000 static and 400 centrifuge experiments were performed, and if g-loads caused
      loss of vision the cosmonaut remained operational getting audible indication.
      Ergonomic characteristics of the control organs and indicators were high enough
      to guarantee accuracy despite the g-loads comparable with values under static
      conditions. The store of knowledge acquired in those studies does not lose
      significance for the present-day piloted space programs.

PMID- 16999066
TI  - [On medical screening of civilian candidates for cosmonauts by exposure to the
      head-to-pelvis acceleration profiles].
AB  - The subject of analysis was the data on +3 and +5 Gz tolerance of 130 civilian
      non-pilot applicants for cosmonauts (men and women, aged 23 to 55) gathered over
      the past 30 years. Length of the centrifuge arm was 7.25 meters and the total
      number of primary centrifuge runs was 309. For nearly every second of the
      applicants (46.7%) acceleration at +5 Gz was an ordeal causing distinct vascular
      or coronary decompensation. Thus, 29.7% exhibited various combinations of brief
      visual disturbances, tachycardia, tachypnea, and systolic arterial pressure in
      the shoulders; in 17%, visual disturbances and/or their precursors were combined
      with exaggerated cardio-vascular functional parameters, arrhythmia, and serious
      vegetative disorders. Most of those who had failed to endure the first
      centrifugation were unable to improve G tolerance during next runs; indeed, they
      showed negative G-tolerance dynamics. G intolerance grew in significance or was
      exacerbated by new disorders and their combinations. These results testify
      against exposure of non-pilot applicants for cosmonauts to +5 G, during the
      primary medical screening.

PMID- 16999067
TI  - [Magnetocardiographic markers of functional hemodynamic overloading of the right
      atrium].
AB  - Functional hemodynamic overloading of the right atrium can be caused by some of
      the dynamic factors in aviation and space flight. Our purpose was to disclose
      markers of the right atrium functional overloading in 6 normal males during the
      Stange test and Valsalva maneuver. Computerized magnetocardiography was fulfilled
      before (resting subjects), during and after (resting subjects) the breathing
      tests. Testing on a background of the flight dynamic factors resulted in a trend
      toward a more superficial Z-coordinate of the myocardium signal along the whole
      or a greater part of the atrial complex as compared with baseline measurements at
      rest. A supposition has been made that this Z coordinate alteration can be a
      marker of functional hemodynamic overloading of the right atrium associated with
      the breathing tests.

PMID- 16999068
TI  - [Immunoglobulin e and allergen-specific IgE antibodies in cosmonauts before and
      after long-duration missions on the International Space Station].
AB  - Immunoglobulins (IgG, IgA, IgM, IgE), specific IgE-antibodies, and interleukin-4
      (IL-4) were investigated in blood serum of nine cosmonauts before and after 128-
      to 195-day ISS missions. It was shown that long-duration space flight does not
      change significantly the content of serum immunoglobulins, allergen-specific IgE
      antibodies or IL-4. Analysis for probable ratios of the total IgE and IL-4
      contents in the pre- and post-flight periods did not reveal any linear
      correlation of these parameters.

PMID- 16999069
TI  - [Dynamics of operator's efficiency under the condition of long continuous vigil].
AB  - Chambered male test-subjects (n = 8) kept awake over 72 hours. Every one or two
      hours during the initial 67 hours they did a tracking test that took 10 to 15
      minutes. The test required intense tracking of rhythmic light spots with
      unpredictably varying frequency and pressing the button as the frequency changed.
      Time of latent reaction was determined. The variable was shown to extend with the
      confinement and fluctuate with the period of approx. 28 hours. Average values on
      the first sleepless night was longer than the ones on the previous day in all
      subjects with personal difference ranging from 7 to 37% and averaging 21%. That
      is, on the first night everyone was less efficient as compared with the previous
      day which could be excused by fatigue and natural variations in mental efficiency
      known to rise in the day and reduce in the night hours.

PMID- 16999070
TI  - [Dynamics of the structural recovery of the rat's tibia from suspension-produced
      osteopenia].
AB  - The qualitative histomorphometric techniques were used to study the dynamics of
      tibia structural recovery from osteopenia in 30 female rats previously suspended
      by tail for 30 days. The suspension was found to have caused osteopenia in the
      tibial proximal metaphysis that was fully gone only after 60 day; in other words,
      readaptation took twice as much time as the osteopenia development. This fact
      should be taken into consideration by designers of rehabilitative methods.

PMID- 16999071
TI  - [Functional insufficiency of the venous valve apparatus and venous return from
      the lower extremities in humans during the standing test].
AB  - The studies were performed with participation of 16 normal subjects with the US
      Doppler evidence of functional insufficiency of the deep vein valves in a lower
      extremity. Valve insufficiency was of the latent clinical form without symptoms
      of chronic venous insufficiency. Functioning of the contralateral leg venous
      valves was normal in all subjects. Linear velocities of blood flow in the femoral
      vein in both extremities in the horizontal and vertical position were compared.
      In the horizontal position, outflow from the deep vein with valve disfunction was
      1.5 times (p<0.01) higher comparing with the other leg as the control. In
      vertical subjects, outflow from the compromised vein was, on the contrary,
      reduced almost by half as compared with the healthy leg. These features of local
      phlebohemodynamics at the outlet of insufficient vein appear to determine the
      intensity of passive mechanic blood redistribution driven by the gravity.

PMID- 16999072
TI  - [Results of aromatherapeutic rehabilitation of women after extended exposure in
      altitude chamber for recompression treatment].
AB  - In recent years recreational diving has gained popularity among women. Occasional
      decompression sickness and pulmonary barotraumata are cured with the use of
      recompression tables. To evaluate factors in therapeutic recompression,
      experiment Rusalka-2004 (Mermaid) was performed with participation of a female
      crew "descended" at air pressure of 70 m H2O and maintained in hyperoxic (pO2 =
      0.45-0.5 kgs/cm2) heliox at 40-0 m H2O for four days. On "ascent" the crew was
      given a course of aroma rehabilitation. To assess effects of this therapy,
      entries in a dedicated questionnaire were made and the Spilberger-Khanin SAM
      (self-appraisal-activity-mood) test and a modification of the Dembau--Rubinshtein
      self-appraisal method were fulfilled on the daily basis. The best result was
      achieved in the subjects who were particularly favourable to this sensory
      stimulation and made own choice of scents of 100% natural essences.

PMID- 16999073
TI  - [The mathematical model of the blood circulation and external respiration
      functional state during high-pressure oxygenation or hyperoxia].
AB  - Based on the minimal energy uptake, the proposed mathematical model of blood
      circulation and external respiration functioning during high-pressure oxygenation
      or hyperoxia allows solution of the optimization task with restrictions dictated
      by adequate functioning of the two systems. Optimal levels of oxygen and carbon
      dioxide pressure in arterial and venous blood, minute blood volume and alveolar
      ventilation as a function of O2 partial pressure in inspired gas mixture were
      determined. Calculations are compared with experimentally derived values.

PMID- 16999074
TI  - [Air quality monitoring on the International Space Station].
AB  - Chemical contamination of air in space cabins occurs mainly due to permanent
      offgassing of equipment and materials, and leaks. Methods and means of
      qualitative and quantitative air monitoring on the ISS are powerful enough as for
      routine so emergency (e.g. local fire, toxic leak) air control. The ISS air
      quality has suited to the adopted standards and crew safety requirements. Yet,
      there is a broad field of action toward improvement of the space cabin air
      monitoring.

PMID- 16999076
TI  - [The acceleration of ultrastructure changes of synapses in somatosensory cortex
      of the rats at repeated simulation of weightlessness effects].
AB  - The electronmicroscopica/study of brain somatosensory cortex in the rats, exposed
      to postponed for a long time repeated lack of support load on hindlimbs by means
      of tail-suspension, has been revealed in hindlimb area of cortex the changes of
      ultrastructure of axodendritic synapses and neurons pointing out the acceleration
      of decrease in functional activity of synapses and neurons in 3-4 layers at
      postponed for a long time repeated simulation of weightlessness effects.

PMID- 16999075
TI  - [Ecological/hygienic and toxicological evaluation of combustion products of
      aviation kerosene and liquefied natural gas].
AB  - Products of kerosene combustion in the present-day aeroengines contain more than
      200 compounds of incomplete combustion, partial oxidation, and thermal
      decomposition of fuel and oil. Most of these are strong toxicants for humans.
      Increase of temperature in the turbine engine combustion chamber led to
      production of very toxic nitrogen oxides. In search for the ecologically safe and
      less toxic alternative attention of fuel engineers was drawn to liquefied natural
      gas which compares well and even excels kerosene in ecological, economic and many
      other respects.

PMID- 16999077
TI  - [Improvement of the reliability of air crew spatial orientation with the psycho
      educational methods].
AB  - A dedicated psycho-educational complex showed itself highly efficient when
      applied to 111 aviation cadets in order to improve the spatial orientation
      ability in future flights.

PMID- 16999078
TI  - [In-flight maintenance and repair of equipment of long-operating orbital
      stations].

PMID- 16999079
TI  - Energy diversity brings stability.

PMID- 16999080
TI  - Lead in water linked to coagulant.

PMID- 16999081
TI  - Easing Vietnam's arsenic crisis.

PMID- 16999082
TI  - Plasticizers go from breast milk to baby.

PMID- 16999083
TI  - Getting religious about air pollution.

PMID- 16999084
TI  - Dioxin diminishes in market meats.

PMID- 16999085
TI  - Fueling the future with citrus waste.

PMID- 16999086
TI  - Microbial fuel cells--challenges and applications.

PMID- 16999087
TI  - Microbial fuel cells: methodology and technology.
AB  - Microbial fuel cell (MFC) research is a rapidly evolving field that lacks
      established terminology and methods for the analysis of system performance. This
      makes it difficult for researchers to compare devices on an equivalent basis. The
      construction and analysis of MFCs requires knowledge of different scientific and
      engineering fields, ranging from microbiology and electrochemistry to materials
      and environmental engineering. Describing MFC systems therefore involves an
      understanding of these different scientific and engineering principles. In this
      paper, we provide a review of the different materials and methods used to
      construct MFCs, techniques used to analyze system performance, and
      recommendations on what information to include in MFC studies and the most useful
      ways to present results.

PMID- 16999088
TI  - Challenges and constraints of using oxygen cathodes in microbial fuel cells.
AB  - The performance of oxygen reduction catalysts (platinum, pyrolyzed iron(ll)
      phthalocyanine (pyr-FePc) and cobalt tetramethoxyphenylporphyrin (pyr-CoTMPP)) is
      discussed in light of their application in microbial fuel cells. It is
      demonstrated that the physical and chemical environment in microbial fuel cells
      severely affects the thermodynamics and the kinetics of the electrocatalytic
      oxygen reduction. The neutral pH in combination with low buffer capacities and
      low ionic concentrations strongly affect the cathode performance and limit the
      fuel cell power output. Thus, the limiting current density in galvanodyanamic
      polarization experiments decreases from 1.5 mA cm(-2) to 0.6 mA cm(-2) (pH 3.3,
      E(cathode) = 0 V) when the buffer concentration is decreased from 500 to 50 mM.
      The cathode limitations are superposed by the increasing internal resistance of
      the MFC that substantially contributes to the decrease of power output. For
      example, the maximum power output of a model MFC decreased by 35%, from 2.3 to
      1.5 mW, whereas the difference between the electrode potentials (deltaE =
      E(anode) - E(cathode)) decreased only by 10%. The increase of the catalyst load
      of pyr-FePc from 0.25 to 2 mg cm(-2) increased the cathodic current density from
      0.4 to 0.97 mA cm(-2) (pH 7, 50 mM phosphate buffer). The increase of the load of
      such inexpensive catalyst thus represents a suitable means to improve the cathode
      performance in microbial fuel cells. Due to the low concentration of protons in
      MFCs in comparison to relatively high alkali cation levels (ratio C(Na+,K+)/C(H+)
      = 5 x E5 in pH 7, 50 mM phosphate buffer) the transfer of alkali ions through the
      proton exchange membrane plays a major role in the charge-balancing ion flux from
      the anodic into the cathodic compartment. This leads to the formation of pH
      gradients between the anode and the cathode compartment.

PMID- 16999089
TI  - A bipolar membrane combined with ferric iron reduction as an efficient cathode
      system in microbial fuel cells.
AB  - There is a need for alternative catalysts for oxygen reduction in the cathodic
      compartment of a microbial fuel cell (MFC). In this study, we show that a bipolar
      membrane combined with ferric iron reduction on a graphite electrode is an
      efficient cathode system in MFCs. A flat plate MFC with graphite felt electrodes,
      a volume of 1.2 L and a projected surface area of 290 cm2 was operated in
      continuous mode. Ferric iron was reduced to ferrous iron in the cathodic
      compartment according to Fe(3+) + e(-) --> Fe2+ (E0 = +0.77 V vs NHE, normal
      hydrogen electrode). This reversible electron transfer reaction considerably
      reduced the cathode overpotential. The low catholyte pH required to keep ferric
      iron soluble was maintained by using a bipolar membrane instead of the commonly
      used cation exchange membrane. For the MFC with cathodic ferric iron reduction,
      the maximum power density was 0.86 W/m2 at a current density of 4.5 A/m2. The
      Coulombic efficiency and energy recovery were 80-95% and 18-29% respectively.

PMID- 16999090
TI  - Effects of membrane cation transport on pH and microbial fuel cell performance.
AB  - Due to the excellent proton conductivity of Nafion membranes in polymer
      electrolyte membrane fuel cells (PEMFCs), Nafion has been applied also in
      microbial fuel cells (MFCs). In literature, however, application of Nafion in
      MFCs has been associated with operational problems. Nafion transports cation
      species other than protons as well, and in MFCs concentrations of other cation
      species (Na+, K+, NH4+, Ca2+, and Mg2+) are typically 10(5) times higher than the
      proton concentration. The objective of this study, therefore, was to quantify
      membrane cation transport in an operating MFC and to evaluate the consequences of
      this transport for MFC application on wastewaters. We observed that during
      operation of an MFC mainly cation species other than protons were responsible for
      the transport of positive charge through the membrane, which resulted in
      accumulation of these cations and in increased conductivity in the cathode
      chamber. Furthermore, protons are consumed in the cathode reaction and,
      consequently, transport of cation species other than protons resulted in an
      increased pH in the cathode chamber and a decreased MFC performance. Membrane
      cation transport, therefore, needs to be considered in the development of future
      MFC systems.

PMID- 16999091
TI  - An upflow microbial fuel cell with an interior cathode: assessment of the
      internal resistance by impedance spectroscopy.
AB  - An upflow microbial fuel cell (UMFC) system with a U-shaped cathode inside the
      anode chamber was developed and produced a maximum volumetric power of 29.2 W/m3
      at a volumetric loading rate of 3.40 kg COD/(m3 day) and an operating temperature
      of 35 degrees C while feeding sucrose continuously. The Coulombic efficiency
      decreased from 51.0% to 10.6% with the increase in the volumetric loading rate
      from 0.57 to 4.29 kg COD/(m3 day). In addition, the lab-scale UMFC maintained
      soluble chemical oxygen demand (COD) removal efficiencies exceeding 90% and
      volatile fatty acid concentrations of approximately 40 mg/L, indicating efficient
      wastewater treatment. The analysis of impedance spectroscopy, generated by
      fitting experimental data into an equivalent circuit, revealed that at a
      volumetric loading rate of 3.40 kg COD/(m3 day) the overall internal resistance
      was 17.13 omega. This internal resistance was composed of electrolyte resistance
      (8.62 omega), charge-transfer resistance (7.05 omega), and diffusion resistance
      (1.46 omega). Electrolyte resistance dominated throughout the entire range of
      loading rates. In addition, impedance spectroscopy demonstrated that both the
      anodic and the cathodic charge-transfer resistances were important limiting
      factors. To further improve the power output of the UMFC, we must reduce the
      electrolyte resistance by optimizing reactor configuration, reduce the anode
      charge-transfer resistances by selecting superior anodic microbiota, and reduce
      the cathodic charge-transfer resistance by exploring sustainable and efficient
      catalysts.

PMID- 16999092
TI  - Microbial fuel cells for sulfide removal.
AB  - Thus far, microbial fuel cells (MFCs) have been used to convert carbon-based
      substrates to electricity. However, sulfur compounds are ubiquitously present in
      organic waste and wastewater. In this study, a MFC with a hexacyanoferrate
      cathodic electrolyte was used to convert dissolved sulfide to elemental sulfur.
      Two types of MFCs were used, a square type closed to the air and a tubular type
      in which the cathode compartment was open to the air. The square-type MFCs
      demonstrated a potential-dependent conversion of sulfide to sulfur. In the
      tubular system, up to 514 mg sulfide L(-1) net anodic compartment (NAC) day(-1)
      (241 mg L(-1) day(-1) total anodic compartment, TAC) was removed. The sulfide
      oxidation in the anodic compartment resulted in electricity generation with power
      outputs up to 101 mW L(-1) NAC (47 W m(-3) TAC). Microbial fuel cells were
      coupled to an anaerobic upflow anaerobic sludge blanket reactor, providing total
      removals of up to 98% and 46% of the sulfide and acetate, respectively. The MFCs
      were capable of simultaneously removing sulfate via sulfide. This demonstrates
      that digester effluents can be polished by a MFC for both residual carbon and
      sulfur compounds. The recovery of electrons from sulfides implies a recovery of
      energy otherwise lost in the methane digester.

PMID- 16999093
TI  - Critical assessment of chelant-enhanced metal phytoextraction.
AB  - Chelant-enhanced phytoextraction has received a lot of attention in the past
      decade. In theory, this technique could cleanse metal polluted soils by
      solubilizing contaminating metals, allowing them to be taken up by plants that
      would subsequently be removed from the site. We review the processes of metal
      solubilization, uptake by plants, and leaching during chelant-enhanced
      phytoextraction. A large excess of chelant is required to solubilize the target
      metal due to the co-solubilization of Ca and Fe. Chelated metals are taken up via
      the apoplastic pathway. Disruption of the Casparian Band is required to achieve
      the high shoot concentrations needed for phytoextraction. Therefore, adding
      chelants to a soil increases not only the total dissolved metal concentration but
      also changes the primary route of plant metal-uptake from the symplastic to the
      apoplastic pathway. Depending on metal, plant species, and chelant concentration,
      significant increases in metal uptake are likely. Soil solution chelate
      concentrations of at least several mM are required to induce appreciable shoot
      concentrations. A simple calculation reveals that at such soil solution
      concentrations plants will remove only a small fraction of the solubilized
      metals. Leaching, exacerbated by preferential flow processes, is unavoidable.
      Chelant-enhanced phytoextraction is therefore limited to areas where the
      connection with groundwater has been broken, orwhere leaching is unimportant.
      Chelant-enhanced phytoextraction may nonetheless have a role in enhancing the
      uptake of essential trace metals. Such a role warrants further investigations
      into the use of biodegradable chelants such as ethylenediaminedisuccinic acid
      (EDDS).

PMID- 16999094
TI  - Electrodialysis with bipolar membranes for sustainable development.
AB  - Electrodialysis with bipolar membranes (EDBM) is a kind of technology that
      integrates solvent and salt dissociation. It can realize salt conversion without
      second salt pollution or provide H+ and OH-/alkoxide ions in situ without salt
      introduction. Thus, it inherently possesses economical and environmental
      benefits. Moreover, its technological compatibility gives rise to new functions
      when it couples with other technologies, such as complexion, ion exchange,
      extraction, and adsorption. In view of the above peculiarities, EDBM has found
      many interesting applications in chemistry, food processing, biochemical
      industries, and environmental protection. However, its development has been
      restricted by such factors as lack of recognition of its contribution to
      industrial ecology, high membrane cost, insufficient research investment, and
      scarce operation experience. This paper compiles an introduction to this
      technology from the perspective of industrial ecology and conducts an extensive
      examination into EDBM applications. Its purpose is to gather synergic strength
      from academia, industry, and government to perfect EDBM for sustainable
      development.

PMID- 16999095
TI  - Exposure of churchgoers to airborne particles.
AB  - Particle mass and number measurements in a church indicate significant increases
      of indoor particle concentrations during the burning of incense. Generally,
      varying concentration regimes can be attributed to different "modes of indoor
      activity" and emission sources. While periods of candle burning are negligible
      concerning particle concentrations, increases by a factor of 6.9 and 9.1 during
      incense burning were observed for PM10 and PM1, respectively. At maximum, indoor
      PM10 shows an 8.1-fold increase in comparison to outdoor measurements. The
      increase of particles < 2 microm is significantly enhanced in comparison to
      larger particles. Due to a particle decay rate of 0.9 h(-1) post-service
      concentrations are elevated for a time span of approximately 24 h above indoor
      background concentrations.

PMID- 16999096
TI  - Wintertime organic aerosols in Christchurch and Auckland, New Zealand:
      contributions of residential wood and coal burning and petroleum utilization.
AB  - Wintertime PM10 samples from two New Zealand cities (Christchurch and Auckland)
      have been characterized using gas chromatography - mass spectrometry for biomass
      burning tracers, hopanes, n-alkanes, fatty acids, n-alkanols and sugars. The
      aerosol samples of Christchurch, which were heavily influenced by residential
      wood and coal burning, showed substantially higher ambient concentrations for
      most of the organic compounds than those of Auckland, where major sources of
      aerosols were vehicular emissions and sea-salt. Mass ratios between the biomass
      burning tracers studied were found to be significantly different (e.g., beta
      sitosterol to nssK+ ratios were more than three times higher in Christchurch than
      in Auckland), although levoglucosan to nssK+ ratios were similar at the both
      sites. We also estimated, for the first time using stereochemical configurations
      of hopanes, that 60% of fossil fuel emissions came from petroleum utilization
      with the remaining 40% being from coal burning in Christchurch. In contrast,
      contribution of coal burning was negligible in Auckland. Moreover, contributions
      of most biomass burning tracers to organic carbon (OC) were significantly higher
      in Christchurch than in Auckland. On the other hand, saccharides (excluding
      levoglucosan) and hopanes accounted for larger fractions of OC in Auckland. This
      study demonstrates that intensive wood and coal burning can significantly affect
      organic aerosol composition in an urban environment.

PMID- 16999097
TI  - Ozone-initiated secondary emission rates of aldehydes from indoor surfaces in
      four homes.
AB  - Field experiments were conducted in four homes during summerto quantify ozone
      induced secondary emission rates (SERs) of aldehydes on indoor surfaces. Four
      surfaces in each house were examined: living room carpet, living room wall,
      kitchen floor, and kitchen counter. Upon exposure to ozone for 3 h, formaldehyde
      and C3-C10 saturated aldehydes, especially nonanal, were emitted as products of
      ozone-surface reactions. Carpet in newer homes had higher SERs than carpet in
      older homes. For example, the nonanal SER from the living room carpet was 80
      microg m(-2) h(-1) in a 1 year old home, but only 8-20 microg m(-2) h(-1) in two
      homes that were greater than 10 years old. All kitchen countertops were very
      reactive and high SERs were observed, especially for nonanal. Product yields from
      countertops were consistent with the products of ozone reactions with oleic and
      linoleic esters, common in cooking oils. These findings suggest that carpet
      surfaces become depleted of reactants as they become oxidized over time. However,
      countertop surfaces, which are cleaned frequently or become covered in cooking
      oils, are continuously replenished with reactants. Over time, countertops may
      become the dominant contributor to indoor concentrations of secondary aldehydes.
      However, when total surface area is taken into account for the homes assessed,
      carpet is predicted to be the primary source of secondary emissions, even for
      older homes.

PMID- 16999098
TI  - TBT causes regime shift in shallow lakes.
AB  - Tributyltin (TBT) is an organotin compound used since the early 1960s as a
      biocide in boat antifouling paints. Its use has been linked to a host of negative
      effects in marine ecosystems including malformations and imposex in Mollusca and
      acute toxicity in many other aquatic animals. Yet, the consequences of TBT use in
      freshwaters are largely unknown. Here, for the first time we reveal that TBT may
      have caused hitherto unsuspected damage to freshwater ecosystems. Through an
      analysis of dated sediment cores collected from a system of recreationally
      boated, shallow lakes, we show that first evidence of TBT is associated with a
      dramatic loss of submerged vegetation and associated diverse animal communities.
      Cause and effect are difficult to unravel in our study. However, we hypothesize
      that TBT, through reducing populations of grazing organisms in lakes already
      affected by eutrophication, promoted the replacement of macrophytes by
      phytoplankton, ultimately leading to a regime shift in the ecosystem. Our
      findings may have parallels in freshwater ecosystems all over the world.

PMID- 16999099
TI  - Phthalate esters in human milk: concentration variations over a 6-month
      postpartum time.
AB  - The present study investigated the levels of phthalate esters in a total of 86
      human milk samples collected among 21 breast-feeding mothers over a 6-month
      postpartum time. Di(2-ethylhexyl) phthalate (DEHP) was the predominant ester with
      the arithmetic mean value of 222 ng g(-1) (range: 156-398 ng g(-1), 95%
      confidence limit), followed by dibutyl phthalate (DBP), 0.87 (range: 0.62-1.2) ng
      g(-1). Diethyl phthalate (DEP), with a mean of 0.31 ng g(-1), was detected in
      only a small number of samples. Weak correlations between lipid content and
      levels of phthalate esters were observed. The levels of phthalate esters in human
      milk fluctuated over the 6-month period; this may indicate a need for multiple
      sample collection, to calculate average concentrations over the feeding period.
      Multiple sample collection would provide a better estimate of the exposure of
      breast-fed infants to phthalate in human milk. For infants relying on breast
      feeding, the mean daily intake over the first 6-month period considering a 7 kg
      infant consuming 750 g of milk was estimated at 167 microg d(-1) for DEHP and
      less than 1 microg d(-1) for DBP and DEP. While the nutritional and social
      benefits of breast-feeding are well established, the potential transfer of
      phthalate esters from mothers to breast-fed infants should also be recognized.

PMID- 16999100
TI  - Consequences of treated water recycling as regards pharmaceuticals and drugs in
      surface and ground waters of a medium-sized Mediterranean catchment.
AB  - In Mediterranean regions where the population is rapidly growing, the risk of
      water resource contamination by wastewater is likely to increase. This is the
      case of the Herault watershed (south of France), where the presence of treated
      wastewater in surface and ground waters has been shown in a previous study. To
      assess the consequence of these wastewater contaminations as regards
      pharmaceuticals and other organic compounds, 16 common pharmaceuticals
      (amitryptilin, acetylsalicylic acid, carbamazepine, clenbuterol, diazepam,
      diclofenac, doxepin, gemfibrozil, ibuprofen, imipramine, ketoprofen, naproxen,
      nordiazepam, paracetamol, salbutamol, and terbutalin) as well as wastewater
      related pollutants (caffeine, gadolinium anomaly, and boron) were analyzed in
      wells pumped for potable water supply and in two wastewater treatment plant
      (WWTP) effluents. In addition, a monitoring along the Lergue River (the main
      tributary of the Herault River) was achieved to assess pharmaceutical behavior in
      surface waters. Pharmaceuticals and other wastewater-related contaminants are
      present in several reservoirs tapped for drinking water, confirming wastewater
      contamination; paracetamol, caffeine, and diclofenac are the most frequently
      detected. Paracetamol is present at rather high concentrations (up to 11 microg/L
      and 211 ng/L, respectively, in a wastewater effluent and in a drinking water
      sample). Though degradable in WWTP, caffeine is commonly encountered in surface
      waters and detected in highly polluted groundwater. On the contrary,
      acetylsalicylic acid concentrations are generally low despite a large consumption
      in France; this is related to its metabolism in humans and rapid degradation in
      the aquatic environment. The monitoring of pharmaceuticals along the Lergue River
      shows that dilution is sufficient to decrease pharmaceutical values.

PMID- 16999101
TI  - Spatial and annual variability in concentrations and sources of Escherichia coli
      in multiple watersheds.
AB  - Nonpoint source fecal contamination is a concern for drinking water supplies
      worldwide. In this study, 4812 E. coli isolates were classified to source.
      Results of this experiment show that the fecal coliform (FC) counts varied by
      year, month, and site, for each of the watersheds sampled. For both years, the
      lowest FC counts tended to be at the highest elevation sites followed by the
      drinking water intake sites at the lowest elevation. The highest FC counts tended
      to be at the mid-elevation sites on BX, Deer, and Duteau Creeks. The sources of
      E. coli varied significantly with stream for 2003 and 2004 (P < 0.001, df = 39),
      although the main sources of E. coli (avian, deer/elk, canine, rodent, bovine,
      and bear) tended to be similar between watersheds. The dominant sources of E.
      coli changed from 2003 (avian, deer/elk, and canine) to 2004 (avian, bovine, and
      rodent). It is important to look at the results of more than 1 year of source
      tracking data to get a better picture of the dominant sources within a watershed.
      Overall, wildlife was the largest contributor of E. coli to the watersheds in
      both 2003 (> 84%) and 2004 (> 73%).

PMID- 16999102
TI  - Accumulation of organochlorines and brominated flame retardants in the eggs and
      nestlings of great tits, Parus major.
AB  - Insectivorous birds may be very useful sentinels for local point-source
      contamination with persistent pollutants, such as polychlorinated biphenyls
      (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides
      (OCPs). Eggs have been used extensively to monitor lipophilic contaminants, as
      females can pass contaminants stored in their body tissues into their eggs.
      Concentrations and profiles in eggs therefore relate to contamination in the
      female. Because nestlings are raised on food items collected locally, it is
      expected that the body burden in nestlings would reflect their diet and local
      pollution levels better than eggs. In this study we compared the accumulation and
      the profile of PCBs, PBDEs, and OCPs in great tit (Parus major) eggs, nestlings
      (5-, 10-, and 15-days old), and their food in two study sites. Our results showed
      that concentrations in great tit eggs were 4 to 6 times higher than those in
      nestlings. Concentrations in nestling great tits corresponded with concentrations
      predicted by a bioenergetics-based model. Most of the persistent organic
      pollutants in 15-day old nestlings were still from maternal origin. The profile
      of these persistent pollutants in eggs and nestlings also gradually changed
      during development. With increasing age, the proportion of the most persistent
      compounds decreased. This study shows that most of the persistent pollutants in
      fully grown nestlings may still be from maternal origin. For nestlings to be
      suitable as indicators of local contamination, most of the POPs they accumulate
      should originate from dietary sources rather than from maternal transfer via the
      egg. Nestling birds may therefore not be good sentinels for local contamination
      with persistent pollutants.

PMID- 16999103
TI  - High-resolution depositional records of polycyclic aromatic hydrocarbons in the
      central continental shelf mud of the East China Sea.
AB  - A well-placed 210Pb-dated sediment core extracted from the distal mud in the
      central continental shelf of the East China Sea is used to reconstruct the high
      resolution atmospheric depositional record of polycyclic aromatic hydrocarbons
      (PAHs), believed to be transported mainly from China in the past 200 years due to
      the East Asian Monsoon. Total PAHs (TPAHs), based on the 16 USEPA priority PAHs,
      range from 27 in 1788 to 132 ng g(-1) in 2001. TPAH variation in the core
      reflects energy usage changes and follows closely the historical economic
      development in China. PAHs in the core are dominantly pyrogenic in source, i.e.,
      they are mainly from the incomplete combustion of coal and biomass burning.
      Several individual PAHs suggest that contribution from incomplete petroleum
      combustion has increased during recent years. Analysis of the 2 + 3 ring and the
      5 + 6 ring PAHs and principle component analysis provide more evidence in the
      change in the energy structure, especially after 1978 when China embarked on the
      "Reform and Open" Policy, indicating the transformation from an agricultural to
      an industrial economy of China. The historical profile of PAH distribution in the
      study area is obviously different from the United States and Europe due to their
      difference in energy structure and economic development stages.

PMID- 16999104
TI  - Trends in anthropogenic mercury emissions in China from 1995 to 2003.
AB  - We have developed multiple-year inventories of anthropogenic mercury emissions in
      China for 1995 through 2003. We estimate that total Hg emissions from all
      anthropogenic sources increased at an average annual rate of 2.9% during the
      period 1995-2003, reaching 696 (+/- 307) t in 2003, with a speciation split of
      395 t of Hg0, 230 t of Hg2+, and 70 t of Hg(p). Nonferrous metals smelting and
      coal combustion continue to be the two leading mercury sources in China, as
      nonferrous metals production and coal consumption keep increasing. Nonferrous
      metals smelting and coal combustion together contributed approximately 80% of
      total Hg emissions during the past decade. Hg emissions from coal combustion
      increased from 202 t in 1995 to 257 t in 2003 at an average annual rate of 3.0%.
      Among all of the coal consumption sectors, the power sector is the leading one in
      Hg emissions growth, up by 5.9% annually. Hg emissions from nonferrous metals
      smelting increased from 230 t in 1995 to 321 t in 2003 at an average annual rate
      of 4.2%. Although Hg emissions related to gold smelting decreased since 1996,
      other nonferrous metals such as zinc, lead, and copper contributed significant Hg
      growth at annual rates of 8.5%, 13.0%, and 6.9%, respectively. At provincial
      level, the trends of Hg emissions show significant variation. The uncertainty
      level decreased from +/- 78% (95% confidence interval) in the estimate of total
      emissions in 1995, to +/- 44% in 2003. This is primarily attributed to the
      decreased emissions from those Hg sources with the largest uncertainty in both
      activity levels and emission factors, such as artisanal gold smelting, mercury
      mining, and battery/fluorescent lamp production.

PMID- 16999105
TI  - Dispersion of heavy metals (metalloids) in soils from 800-year-old pollution
      (Mont-Lozere, France).
AB  - Numerous palaeo metallurgical sites (n = 70) characterized by slag presenting a
      homogeneous typology have been reported on the Mont-Lozere Massif (Southern
      France). These activities took place in the medieval period. The silicated slag
      matrix comprises mainly Pb (25%), Sb (0.4%), and several thousand parts per
      million of As, Cu, and Zn. Soil samples were collected in and around two sites,
      to understand the dispersion mechanism affecting the slag tailings through use of
      metal concentrations and lead isotopic compositions. The majority of polluted
      soil samples show high enrichment factors (EF) for Pb and Sb, slightly lower EFs
      for Cu, and much lower EFs for As and Zn. We show that this "old" metal pollution
      was physically dispersed, through erosion of workshop soils and slag tailings, in
      a restricted area (ca. 200 m down slope form the site). There is no evidence for
      massive leaching of slag metals by soil waters, except for Zn. Thus, the
      pollution is mainly due to the metal-making process, i.e., smoke-fallout, pieces
      of ore, the crackling of smelting ore outside the oven during reduction, and
      charcoal, etc. The lead isotopic compositions of the soils define a binary mixing
      trend between local granite or background soil and slag (which represent the
      workshop soil). Simple mass balance equations using either Pb isotopes or Pb
      concentrations suggest that between 40 and 100% of the total Pb in soils comes
      from the Medieval workshop pollution, leaving any later pollution negligible. The
      large number of sites on the Mont-Lozere means this medieval pollution is
      significant and poses a real environmental risk.

PMID- 16999106
TI  - Geographical stability of enterococcal antibiotic resistance profiles in Europe
      and its implications for the identification of fecal sources.
AB  - This manuscript describes the use of a recently developed microbial source
      tracking (MST) technique to determine sources of fecal bacteria (enterococci)
      from four separate European countries. The investigation aimed to evaluate
      whether the origin of bacterial populations from France, Spain, and Sweden (n =
      456) could be predicted using a library of antibiotic resistance patterns of
      enterococci of known origin assembled in the United Kingdom (n = 2739). Bacterial
      isolates were exposed to a battery of 31 antibiotic tests and classified into
      source groups using discriminant function analysis (DFA). Results showed that
      while on average 72% of the U.K. isolates could be correctly classified as
      originating from either municipal wastewater (MW), livestock, or wild birds, only
      43% of non-U.K. isolates could be successfully classified into the same source
      categories. The results suggested that patterns of resistance amongst isolates
      contained in the U.K. library were not representative of those found in the other
      locations and that it may not be possible to share libraries over large
      distances, such as those in this study. Future MST studies using antibiotic
      resistance analysis (ARA) in Europe may therefore require the assembly of
      watershed specific libraries, increasing the cost of such studies.

PMID- 16999107
TI  - Polychlorinated naphthalenes in Great lakes air: assessing spatial trends and
      combustion inputs using PUF disk passive air samplers.
AB  - Passive air samplers made from polyurethane foam (PUF) disks housed in stainless
      steel chambers were deployed over four seasons during 2002-2003, at 15 sites in
      the Laurentian Great lakes, to assess spatial and temporal trends of
      polychlorinated naphthalenes (PCNs). Sampling rates, determined using depuration
      compounds pre-spiked into the PUF disk prior to exposure, were, on average, 2.9
      +/- 1.1 m3 d(-1), consistent with previous studies employing these samplers. PCN
      air concentrations exhibited strong urban-rural differences-typically a few pg m(
      3) at rural sites and an order of magnitude higher at urban sites (Toronto, 12-31
      pg m(-3) and Chicago,13-52 pg m(-3)). The high concentrations at urban sites were
      attributed to continued emissions of historically used technical PCN.
      Contributions from combustion-derived PCNs seemed to be more important at rural
      locations where congeners 24 and 50, associated with wood and coal burning, were
      elevated. Congener 66/67, associated with incineration and other industrial
      thermal processes, was elevated at two sites and explained by nearby and/or
      upwind sources. Probability density maps were constructed for each site and for
      every integration period were shown to be a useful complement to seasonally
      integrated passive sampling data to resolve source-receptor relationship for PCNs
      and other pollutants.

PMID- 16999108
TI  - Statistically designed survey of polychlorinated dibenzo-p-dioxins,
      polychlorinated dibenzofurans, and co-planar polychlorinated biphenyls in U. S.
      meat and poultry, 2002-2003: results, trends, and implications.
AB  - To obtain information on dioxin levels in the human diet, the Food Safety and
      Inspection Service of the United States Department of Agriculture recently
      determined levels of dioxin-like compounds (dioxins/dibenzofurans/PCBs) in four
      major slaughter classes (steers and heifers, market hogs, young chickens, and
      young turkeys) that comprise over 90% of the meat and poultry production in the
      United States. The data were analyzed and compared to data from smaller surveys
      carried out from 1994 to 1996. These surveys were conducted by different
      laboratories nearly 10 years apart, so a direct comparison of the data was not
      straightforward. Three approaches were taken: (1) comparison with nondetects set
      to zero, (2) comparison with nondetects set to half the limit of detection, and
      (3) comparison applying the earlier surveys' limits of detection to the newer
      data. The data analyses indicated that dioxin levels appear to have declined in
      three of the four slaughter classes, with young chickens, market hogs, and young
      turkeys declining 20-80%, while any declines in cattle dioxin levels, if real,
      are less than those observed in the other slaughter classes. Further study is
      needed to examine factors that might explain the differences in dioxin levels and
      distribution profiles in the four slaughter classes. A small number of market hog
      and steers/ heifers samples had dioxin toxic equivalency levels (TEQs) greater
      than 2 pg/g lipid weight. Follow-up investigations for those samples indicated a
      common source for the market hog samples (a dioxin-contaminated mineral
      supplement), but no commonality was found for the steers/ heifers samples.

PMID- 16999109
TI  - PCBs, PCDD/Fs, and organochlorine pesticides in farmed Atlantic salmon from
      Maine, eastern Canada, and Norway, and wild salmon from Alaska.
AB  - Farmed Atlantic salmon (Salmo salar) from Maine and eastern Canada, wild Alaskan
      Chinook salmon (Oncorhynchus tshawytscha), and organically farmed Norwegian
      salmon samples were analyzed for the presence of polychlorinated biphenyls
      (PCBs), dioxin-like PCBs, polychlorinated dibenzo-p-dioxins (PCDDs), dibenzo-p
      furans (PCDFs), and chlorinated pesticides. PCDD and PCDF congeners were not
      detected in > 80% of the samples analyzed. Total PCB concentrations (7.2-29.5
      ng/g, wet weight, ww) in the farmed salmon were significantly higher than those
      in the wild Alaskan Chinook samples (3.9-8.1 ng/g, ww). Concentrations of PCBs,
      WHO PCB TEQs, and chlorinated pesticides varied significantly by region. PCB and
      WHO PCB TEQ concentrations in farmed salmon from eastern Canada were lower than
      those reported in samples collected two years earlier, possibly reflecting recent
      industry efforts to lower contaminant concentrations in feed. Organically farmed
      Norwegian salmon had the highest concentrations of PCBs (mean: 27 ng/g, ww) and
      WHO PCB TEQs (2.85 pg/g,ww); their TEQ values are in the higher range of those
      reported in farmed salmon from around the world. Removal of skin from salmon
      fillets resulted in highly variable reductions of lipids and contaminants, and in
      some skin-off samples, contaminant levels were higher, suggesting that skin
      removal does not protect the consumer from health risks associated with
      consumption of farmed salmon.

PMID- 16999110
TI  - Size distribution characteristics of elemental carbon emitted from Chinese
      vehicles: results of a tunnel study and atmospheric implications.
AB  - The size distribution characteristics of elemental carbon (EC) emissions from
      Chinese vehicles have not been previously described. In this study, we collected
      size-segregated aerosol samples using a 10-stage MOUDI sampler (0.056-18 microm)
      in the Zhujiang tunnel, a roadway tunnel in the urban area of Guangzhou, China.
      The samples were analyzed for EC, organic carbon (OC), and inorganic ions. Fine
      particles had an OC/EC ratio of 0.57, indicating a dominant contribution of EC
      from diesel vehicles. Both EC and OC showed a dominant accumulation mode with a
      mass median aerodynamic diameter (MMAD) of 0.42 microm. In comparison, studies
      available in the literature typically reported a much lower MMAD for EC
      (approximately 0.1 microm) in vehicular emissions in North America. A theoretical
      analysis indicated that the larger EC particles observed in this study could not
      have resulted from after-emission growth processes (i.e., water accretion,
      coagulation, and vapor condensation). This leaves operating conditions such as
      high engine loads and low combustion efficiencies, which are more prevalent in
      diesel-fueled Chinese vehicles, as a more plausible inherent reason for producing
      the larger EC agglomerates. While fresh 0.1 microm EC particles are unlikely to
      act as cloud condensation nuclei (CCN), calculations showed that EC particles as
      large as 0.42 microm are effective CCN at atmospherically relevant critical
      supersaturation values of less than 1%. As a result, fresh EC particles from
      Chinese vehicle emissions could readily undergo cloud processing and form
      internal mixtures with sulfate in the residue droplet mode particles. This
      prediction is consistent with observations that EC frequently showed a dominant
      droplet mode in urban atmospheres in this region. The internal mixing of EC with
      highly hygroscopic sulfate would facilitate its removal by wet deposition and
      shorten its lifetime in the atmosphere. In addition, the light-absorbing
      capabilities of EC particles could also be enhanced due to their internal mixing
      with sulfate. Numerical aerosol models need to take these factors into
      consideration for better predictions of the behaviors and effects of urban
      aerosols in China.

PMID- 16999111
TI  - Investigating ebullition in a sand column using dissolved gas analysis and
      reactive transport modeling.
AB  - Ebullition of gas bubbles through saturated sediments can enhance the migration
      of gases through the subsurface, affect the rate of biogeochemical processes, and
      potentially enhance the emission of important greenhouse gases to the atmosphere.
      To better understand the parameters controlling ebullition, methanogenic
      conditions were produced in a column experiment and ebullition through the column
      was monitored and quantified through dissolved gas analysis and reactive
      transport modeling. Dissolved gas analysis showed rapid transport of CH4
      vertically through the column at rates several times faster than the bromide
      tracer and the more soluble gas CO2, indicating that ebullition was the main
      transport mechanism for CH4. An empirically derived formulation describing
      ebullition was integrated into the reactive transport code MIN3P allowing this
      process to be investigated on the REV scale in a complex geochemical framework.
      The simulations provided insights into the parameters controlling ebullition and
      show that, over the duration of the experiment, 36% of the CH4 and 19% of the CO2
      produced were transported to the top of the column through ebullition.

PMID- 16999112
TI  - Sorption equilibrium of a wide spectrum of organic vapors in Leonardite humic
      acid: experimental setup and experimental data.
AB  - The environmental fate of volatile and semivolatile organic compounds is
      determined by their partitioning between air and soil constituents, in particular
      soil organic matter (SOM). While there are many studies on the partitioning of
      nonpolar compounds between water and SOM, data on sorption of polar compounds and
      data for sorption from the gas phase are rather limited. In this study,
      Leonardite humic acid/air partition coefficients for 188 polar and nonpolar
      organic compounds at temperatures between 5 and 75 degrees C and relative
      humidities between < 0.01% and 98% have been determined using a dynamic flow
      through technique. To the best of our knowledge, this is by far the largest and
      most diverse and consistent data set for sorption into humic material published
      so far. The major results are as follows: the relative humidity affected the
      experimental partition coefficients by up to a factor of 3; polar compounds
      generally sorbed more strongly than nonpolar compounds due to H-bonding (electron
      donor/ acceptor interactions) with the humic acid; no glass transitions in the
      range of 5-75 degrees C that would be relevant with respect to the sorption
      behavior of hydrated Leonardite humic acid were observed; our experimental data
      agree well with experimental partition coefficients from various literature
      sources.

PMID- 16999113
TI  - Sorption equilibrium of a wide spectrum of organic vapors in Leonardite humic
      acid: modeling of experimental data.
AB  - In a recent publication we presented experimental Leonardite humic acid/air
      partition coefficients for 188 polar and nonpolar organic compounds measured with
      one consistent method. In this paper these experimental data are evaluated with
      various model predictions. For the PcKocWIN model some major shortcomings become
      apparent. The octanol-based Karickhoff-model exhibits a good performance for the
      nonpolar compounds but not for the polar ones. A good description of the whole
      data set is achieved with a polyparameter linear free energy relationship (pp
      LFER) that explicitly accounts for the nonpolar (van der Waals and cavity
      formation) and polar (electron donor/acceptor) interactions between the sorbate
      molecule and the sorbent phase. With this pp-LFER model, most of the humic
      acid/air partition coefficients could be predicted within a factor of 2. The pp
      LFER model also successfully predicts organic-C/water partition coefficients
      (K(ioc)) collected from the literature when it is combined with a pp-LFER for
      air/water partition coefficients. This supports our earlier conclusion that the
      thermodynamic cycle is applicable in the humic acid/water/air system. Based on
      our experimental data, we present a pp-LFER-model for humic acid/air and humic
      acid/water partitioning at any ambient temperatures.

PMID- 16999114
TI  - Evidence for the aquatic binding of arsenate by natural organic matter-suspended
      Fe(III).
AB  - Dialysis experiments with arsenate and three different NOM samples amended with
      Fe(lll) showed evidence confirming the formation of aquatic arsenate-Fe(Ill)-NOM
      associations. A linear relationship was observed between the amount of complexed
      arsenate and the Fe(lll) content of the NOM. The dialysis results were consistent
      with complex formation through ferric iron cations acting as bridges between the
      negatively charged arsenate and NOM functional groups and/or a more colloidal
      association, in which the arsenate is bound by suspended Fe(lll)-NOM colloids.
      Sequential filtration experiments confirmed that a significant proportion of the
      iron present at all Fe/C ratios used in the dialysis experiments was colloidal in
      nature. These colloids may include larger NOM species that are coagulated by the
      presence of chelated Fe(lll) and/or NOM-stabilized ferric (oxy)hydroxide
      colloids, and thus, the solution-phase arsenate-Fe(Ill)-NOM associations are at
      least partially colloidal in nature.

PMID- 16999115
TI  - Pseudopolarographic determination of Cd2+ complexation in freshwater.
AB  - Pseudopolarography was used to detect Cd2+ complexes in samples collected at
      several locations along the Potomac River in June and September, 2004.
      Irrespective of site and sampling time, no weak inorganic Cd2+ species were
      present. However, up to two stable Cd(2+)-organic complexes were detected at each
      site. These unknown Cd2+ complexes were characterized by their half-wave
      potential (E1/2). The E1/2 values indicated certain Cd2+ complexes were common at
      different sites during each sampling but different complexes were observed in
      June and September. A Cd2+ chelate scale, generated from model ligands, was used
      to estimate the thermodynamic stability constants (K(THERM)) of the unknown
      complexes, which ranged from log K(THERM) = 21.5-32.0. Pseudopolarography did not
      recover all Cd2+ in the samples. This was partly attributed to highly stable Cd
      sulfide species; owing to the presence of acid volatile sulfide at concentrations
      greater than total dissolved Cd2+. These electrochemically inert species may be
      multinuclear Cd-sulfide clusters and/ or nanoparticles with K(THERM) values that
      exceed the detection window of pseudopolarography (log K(THERM) > 34.4).

PMID- 16999116
TI  - Biodegradation and product identification of [14C]hexabromocyclododecane in
      wastewater sludge and freshwater aquatic sediment.
AB  - In a previous study the biodegradation of hexabromocyclododecane (HBCD) was
      reported to occur under realistic environmental concentrations in soils and
      freshwater aquatic sediments with biotransformation half-lives ranging from
      approximately 2 days to 2 months. In this study we extend our knowledge as to the
      environmental behavior of HBCD with respect to the fate of the three major
      diastereomers of HBCD (alpha, beta, and gamma) as well as to the identification
      of major intermediate metabolites formed during degradation. Substantial
      biological transformation of the alpha-, beta-, and gamma-[14C]HBCD diastereomers
      was observed in wastewater (i.e., digester) sludge and in freshwater aquatic
      sediment microcosms prepared under aerobic and anaerobic conditions. Concomitant
      with the loss of [14C]HBCD in these matrixes there was a concurrent production of
      three [14C]products. Using a combination of high performance liquid
      chromatography atmospheric pressure photoionization mass spectrometry and gas
      chromatography electron impact ionization mass spectrometry these metabolites
      were identified as tetrabromocyclododecene, dibromocyclododecadiene, and
      cyclododecatriene. We propose that HBCD is sequentially debrominated via
      dihaloelimination where at each step there is the loss of two bromines from
      vicinal carbons with the subsequent formation of a double bond between the
      adjacent carbon atoms. These results demonstrate that microorganisms naturally
      occurring in aquatic sediments and anaerobic digester sludge mediate complete
      debromination of HBCD.

PMID- 16999117
TI  - Experimental and numerical iInvestigations of effects of silica colloids on
      transport of strontium in saturated sand columns.
AB  - Transport experiments with strontium were conducted using saturated sand columns
      in the presence and absence of silica colloids, and numerical modeling was
      performed with modeling results compared to experimental data. The experiments
      were aimed at testing the hypothesis that under certain chemical conditions
      colloids act as movement-retarding agents and yield a larger effective
      retardation factor for the migrating contaminant. Four individual experiments
      were conducted to identify conditions where the mobility of silica colloids is
      increased or decreased, and a similar set was conducted for strontium transport
      in the absence of colloids. Mobility of colloids was found to increase with
      decreasing ionic strength and increasing pH, with the ionic strength having the
      more significant impact. The reverse effect was obtained for strontium. Based on
      these results, two additional experiments were conducted where both colloids and
      strontium were injected at the column inlet. Results showed that under certain
      conditions of ionic strength and pH (I = 3.0 x 10(-2) M and pH = 4-5.4) colloids
      retarded the movement of strontium. The retardation effect was obtained in two
      experiments under slightly modified conditions, which confirms the role of
      colloids as retarding agents. Afinite difference numerical model was used to (a)
      simulate mobile breakthrough curves and compare to experimental data and (b)
      estimate the model parameters describing cotransport of strontium and colloids.
      The model accurately predicted arrival time and the overall shape of the
      breakthrough curves.

PMID- 16999118
TI  - Mechanistic characterization of adsorption and slow desorption of phenanthrene
      aged in soils.
AB  - Long-term adsorption of phenanthrene to soils was characterized in a silt-loam
      (LHS), a sandy soil (SBS), and a podzolized soil (CNS) by use of the Polanyi
      Manes model, a Langmuir-type model, and a black carbon-water distribution
      coefficient (K(BC)) at a relative aqueous concentration (C(e)/S(w)) of 0.002
      0.32. Aqueous desorption kinetic tests and temperature-programmed desorption
      (TPD) were also used to evaluate phenanthrene diffusivities and desorption
      activation energies. Adsorption contribution in soils was 48-70% after 30 days
      and 64-95% after 270 days. Significant increases in adsorption capacity with
      aging suggest that accessibility of phenanthrene to fractions of SBS soil matrix
      was controlled by sorptive diffusion at narrow meso- and micropore constrictions.
      Similar trends were not significant for LHS silt-loam or CNS podzol. Analysis of
      TPD profiles reveal desorption activation energies of 35-53 kJ/mol and
      diffusivities of 1.6 x 10(-7-)9.7 x 10(-8) cm2/s. TPD tests also indicate that
      the fraction of phenanthrene mass not diffusing from soils was located within
      micropores and narrow width mesopores with a corresponding volume of 1.83 x 10(-5
      )6.37 x 10(-5) cm3/g. These values were consistent with the modeled adsorption
      contributions, thus demonstrating the need for such complimentary analytical
      approach in the risk assessment of organic contaminants.

PMID- 16999119
TI  - Product study of the OH, NO3, and O3 initiated atmospheric photooxidation of
      propyl vinyl ether.
AB  - A product study is reported on the gas-phase reactions of OH and NO3 radicals and
      ozone with propyl vinyl ether (PVE). The experiments were performed in a 405 L
      borosilicate glass chamber in synthetic air at 298 +/- 3 K using long path in
      situ FTIR spectroscopy for the analysis of the reactants and products. In the
      presence of NO(x) (NO + NO2) the main products for the OH-radical initiated
      oxidation of PVE were propylformate and formaldehyde with molar formation yields
      of 78.6 +/- 8.8% and 75.9 +/- 8.4%, respectively. In the absence of NO(x)
      propylformate and formaldehyde were formed with molar formation yields of 63.0 +/
      9.0% and 61.3 +/- 6.3%, respectively. In the reaction of NO3 radicals with PVE
      propylformate 52.7 +/- 5.9% and formaldehyde 55.0 +/- 6.3% were again observed as
      major products. The ozonolysis of PVE led to the production of propylformate,
      formaldehyde, hydroxyperoxymethyl formate (HPMF; HC(O)OCH2OOH), and CO with molar
      formation yields of 89.0 +/- 11.4%, 12.9 +/- 4.0%, 13.0 +/- 3.4%, and 10.9 +/-
      2.6%, respectively. The formation yield of OH radicals in the ozonolysis of PVE
      was estimated to be 17 +/- 9%. Simple atmospheric degradation mechanisms are
      postulated to explain the formation of the observed products.

PMID- 16999120
TI  - Aquatic photochemistry of nitrofuran antibiotics.
AB  - The aquatic photochemical degradation of a class of pharmaceuticals known as the
      nitrofuran antibiotics (furaltadone, furazolidone, and nitrofurantoin) was
      investigated. Direct photolysis is the dominant photodegradation pathway for
      these compounds with the formation of a photostationary state between the syn and
      the anti isomers occurring during the first minutes of photolysis. The direct
      photolysis rate constant and quantum yield were calculated for each of the three
      nitrofurans. Reaction rate constants with reactive oxygen species (ROS), 102 and
      *OH, were also measured, and half-lives were calculated using environmentally
      relevant ROS concentrations. Half-lives calculated for reaction with 1O2 and *OH
      are in the ranges of 120-1900 and 74-82 h, respectively. When compared to the
      direct photolysis half-lives, 0.080-0.44 h in mid-summer at 45 degrees N
      latitude, it is clear that indirect photochemical processes cannot compete with
      direct photolysis. The major photodegradation product of the nitrofurans was
      found to be nitrofuraldehyde, which is also photolabile. Upon photolysis,
      nitrofuraldehyde produces NO, which is easily oxidized to nitrous acid. The acid
      produced further catalyzes the photodegradation of the parent nitrofuran
      antibiotics, leading to autocatalytic behavior. Natural waters were found to
      buffer the acid formation.

PMID- 16999121
TI  - Nucleophilic substitution of phosphorothionate ester pesticides with bisulfide
      (HS-) and polysulfides (S(n)2-).
AB  - The reactions of five organophosphorus insecticides (OPs) (chlorpyrifos-methyl,
      parathion-methyl, fenchlorphos, chlorpyrifos, and parathion) with
      hydrogensulfide/ bisulfide (H2S/HS-) and polysulfides (S(n)2-) were examined in
      well-defined aqueous solutions over a pH range from 5 to 9. The rates are first
      order in the concentration of the different reduced sulfur species. Experiments
      at 25 degrees C demonstrated that the reaction of the five OPs with the reduced
      sulfur species follows a SN2 mechanism. The activation parameters of the reaction
      of OPs with bisulfide were determined from the measured second-order rate
      constants over a temperature range of 5-60 degrees C. The determined second-order
      rate constants show that the reaction of an OP with polysulfides is from 15 to 50
      times faster than the reaction of the same OP with bisulfide. The dominant
      transformation products are desalkyl OPs, which indicate that the nucleophilic
      substitution of reduced sulfur species occurs at the carbon atom of the alkoxy
      groups. And also the results show that these reduced sulfur species are much
      better nucleophiles, and thus degrade these pesticides faster than the well
      studied base hydrolysis by OH-. When the determined second-order rate constants
      are multiplied with the concentration of HS- and S(n)2- reported in salt marshes
      and porewater of sediments, predicted half-lives show that abiotic degradation by
      sulfide species may be of comparable importance to microbially mediated
      degradation in anoxic environments.

PMID- 16999122
TI  - Kinetics of 1,4-dioxane biodegradation by monooxygenase-expressing bacteria.
AB  - 1,4-Dioxane is a probable human carcinogen, and an important emerging water
      contaminant. In this study, the biodegradation of dioxane by 20 bacterial
      isolates was evaluated, and 13 were found to be capable of transforming dioxane.
      Dioxane served as a growth substrate for Pseudonocardia dioxanivorans CB1190 and
      Pseudonocardia benzenivorans B5, with yields of 0.09 g protein g dioxane(-1) and
      0.03 g protein g dioxane(-1), respectively. Cometabolic transformation of dioxane
      was observed for monooxygenase-expressing strains that were induced with methane,
      propane, tetrahydrofuran, or toluene including Methylosinus trichosporium OB3b,
      Mycobacterium vaccae JOB5, Pseudonocardia K1, Pseudomonas mendocina KR1,
      Ralstonia pickettii PKO1, Burkholderia cepacia G4, and Rhodococcus RR1. Product
      toxicity resulted in incomplete dioxane degradation for many of the cometabolic
      reactions. Brief exposure to acetylene, a known monooxygenase inhibitor,
      prevented oxidation of dioxane in all cases, supporting the hypothesis that
      monooxygenase enzymes participated in the transformation of dioxane by these
      strains. Further, Escherichia coli TG1/pBS(Kan) containing recombinant plasmids
      derived from the toluene-2- and toluene-4-monooxygenases of G4, KR1 and PKO1 were
      also capable of cometabolic dioxane transformation. Dioxane oxidation rates
      measured at 50 mg/L ranged from 0.01 to 0.19 mg hr(-1) mg protein(-1) for the
      metabolic processes, 0.1-0.38 mg hr(-1) mg protein(-1) for cometabolism by the
      monooxygenase-induced strains, and 0.17-0.60 mg hr(-1) mg protein(-1) for the
      recombinant strains. Dioxane was not degraded by M. trichosporium OB3b expressing
      particulate methane monooxygenase, Pseudomonas putida mt-2 expressing a toluene
      side-chain monooxygenase, and PseudomonasJS150 and Pseudomonas putida F1
      expressing toluene-2,3-dioxygenases. This is the first study to definitively show
      the role of monooxygenases in dioxane degradation using several independent lines
      of evidence and to describe the kinetics of metabolic and cometabolic dioxane
      degradation.

PMID- 16999123
TI  - Influence of pH on the stereoselective degradation of the fungicides
      epoxiconazole and cyproconazole in soils.
AB  - Many pesticides are chiral and consist of two or more enantiomers/stereoisomers,
      which may differ in biological activity, toxicity, effects on nontarget
      organisms, and environmental fate. In the last few years, several racemic
      compounds have been substituted by enantiomer-enriched or single-isomer compounds
      ("chiral switch"). In this context, the stereoselective degradation in soils is
      an important part of a benefit-risk evaluation, but the understanding of the
      environmental factors affecting the chiral preferences is limited. In this study,
      the stereoselective degradation of the fungicides epoxiconazole and cyproconazole
      was investigated in different soils, selected to cover a wide range of soil
      properties. The fungicides were incubated under laboratory conditions and the
      degradation and configurational stability of the stereoisomers were followed over
      time using enantioselective GC-MS with a gamma-cyclodextrin derivative as chiral
      selector. In alkaline and slightly acidic soils, the degradation of epoxiconazole
      was clearly enantioselective, whereas in more acidic soils, both enantiomers were
      degraded at similar rates (overall half-lives 78-184 d). The enantioselectivity,
      expressed as ES = (k(i) - k(j))/ (k(i) + k(j)), ranged from -0.4 in alkaline
      soils (faster degradation of enantiomer j) to approximately 0 in acidic soils
      (non-enantioselective), and showed a reasonably linear correlation with the soil
      pH. The four stereoisomers of cyproconazole (overall half-lives 5-223 d) were
      also degraded at different rates in the various soils, but only the
      stereoselectivities between epimers showed some correlations with pH, whereas
      enantioselectivities did not. Both fungicides were configurationally stable in
      soils, i.e., no enantiomerization or epimerization was observed. Correlations
      between pH and ES have previously been reported for other pesticides (metalaxyl,
      dichlorprop, mecoprop), but the presence or absence of such correlations is not
      obviously linked to the pathways of degradation. It can be assumed that different
      microorganisms and enzymes are involved in the primary degradation of these
      compounds, but on which level soil pH has an influence on ES remains to be
      investigated.

PMID- 16999124
TI  - Polar pollutants entry into the water cycle by municipal wastewater: a European
      perspective.
AB  - The effluents of eight municipal wastewater treatment plants (WWTP) in Western
      Europe were analyzed by liquid-chromatography-mass spectrometry for the
      occurrence of 36 polar pollutants, comprising household and industrial chemicals,
      pharmaceuticals, and personal care products. In a long-term study of the
      effluents of three WWTP over 10 months, sulfophenyl carboxylates and ethylene
      diamino tetraacetate (EDTA) were detected above 10 microg/L on average, while
      benzotriazoles, benzothiazole-2-sulfonate, diclofenac, and carbamazepine showed
      mean concentrations of 1-10 microg/L, followed by some flame retardants,
      naphthalene disulfonates, and personal care products in the range of 0.1-1
      microg/L. Half of the determined compounds were not significantly removed in
      tertiary wastewater treatment. By dividing the effluent concentration of a
      compound by its relative removal in WWTP a water cycle spreading index (WCSI) was
      calculated for each compound. We propose that this index provides a measure for
      the potential of a polar compound to spread along a partially closed water cycle
      after discharge with municipal wastewater and to occur in raw waters used for
      drinking water production. Polar pollutants in surface water samples of different
      catchments showed increasing concentration for compounds with increasing WCSI.

PMID- 16999125
TI  - Biodegradation of short-chain n-alkanes in oil sands tailings under methanogenic
      conditions.
AB  - The biodegradation of a mixture of low molecular weight n-alkanes (C6, C7, C8,
      and C10) was assessed under methanogenic conditions using mature fine tailings
      (MFT) produced by the oil sands industry in Alberta, Canada. Microorganisms
      present in the MFT mineralized the added n-alkane mixture, producing 16.2 (+/-
      0.3) or 20.5 (+/- 0.1) mmol of methane in the headspace of microcosms spiked with
      0.2% or 0.5% w/v n-alkanes, respectively, during 29 weeks of incubation. The
      spiked n-alkanes biodegraded in the sequence C10 > C8 > C7 > C6. Degradation of
      100% C10, 97% C8, 74% C7, and 44% C6 occurred in a mixture of n-alkanes in the
      MFT spiked at 0.2% after 25 weeks of incubation. The same pattern of
      biodegradation was also observed in the MFT spiked with 0.5% n-alkanes.
      Stoichiometric calculations confirmed the mineralization of the degraded n
      alkanes to methane. This study showed that the short-chain n-alkanes, which
      comprise a significant portion of the unrecovered naphtha used in bitumen
      extraction and released into the settling basins, can be biodegraded into
      methane. These findings may influence decisions regarding extraction processes
      and long-term management of MFT, and they suggest that intrinsic, methanogenic
      metabolism of these n-alkanes may occur in other anoxic environments.

PMID- 16999126
TI  - Kinetics and products of photolysis and reaction with OH radicals of a series of
      aromatic carbonyl compounds.
AB  - We have investigated the photolysis and OH radical reactions of phthaldialdehyde,
      2-acetylbenzaldehyde, and 1,2diacetylbenzene, atmospheric reaction products of
      naphthalene and alkylnaphthalenes, and of phthalide, a photolysis product of
      phthaldialdehyde. Using a relative rate method with 1,2,4-trimethylbenzene and
      2,2,3,3-tetramethylbutane as reference compounds, measured rate constants for the
      gas-phase OH radical reactions (in units of 10(-12) cm3 molecule(-1) s(-1)) were
      as follows: phthaldialdehyde, 23 +/- 3; 2-acetylbenzaldehyde, 17 +/- 3; 1,2
      diacetylbenzene, < 1.2; and phthalide, < 0.8. Blacklamp irradiation showed that
      phthaldialdehyde and 2-acetylbenzaldehyde photolyze, and, combined with
      absorption spectra measured in n-hexane solution, average photolysis quantum
      yields of 0.19 and 0.21, respectively, were derived (290-400 nm). No evidence for
      photolysis of 1,2-diacetylbenzene or phthalide by blacklamps was obtained. The
      major atmospheric loss process of phthaldialdehyde and 2-acetylbenzaldehyde are
      estimated to be by photolysis, with photolysis lifetimes of 1.4-1.5 h for a 12-hr
      average NO2 photolysis rate of 0.312 min(-1). Phthalic anhydride was the major
      observed product from the OH radical-initiated reactions of all four compounds
      and was also formed from photolysis of phthaldialdehyde and 2-acetylbenzaldehyde.
      The major photolysis products observed were phthalide from phthaldialdehyde and 3
      methylphthalide from 2-acetylbenzaldehyde.

PMID- 16999127
TI  - Effect of organic co-contaminants on technetium and rhenium speciation and
      solubility under reducing conditions.
AB  - The chemical and biogeochemical reduction of pertechnetate (TcO4-) and perrhenate
      (ReO4-) have been compared alongside complexation of the reduced species by three
      anthropogenic ligands relevant to nuclear waste (ethylenediaminetetraacetic acid
      (EDTA), nitrilotriacetic acid (NTA), and isosaccharinic acid (ISA)). An HPLC size
      exclusion column coupled to ICP-MS was used to separate the species and quantify
      Tc and Re. During method development, ReO4- showed recalcitrance to direct
      chemical reduction by Sn(ll) under conditions that readily reduced TcO4- and
      resulted in Tc(IV)-organic complexes. In microcosm experiments of a silty loam
      soil containing Tc04-, ReO4-, and ISA (3.0 mM), EDTA (0.17 mM), or NTA (2.4 mM),
      anoxia developed to iron-reducing conditions during the 42 day experimental
      period. The majority of the TcO4- was reduced to particle-reactive Tc(IV) and
      removed from solution during nitrate reduction, but there was no chromatographic
      evidence of Tc(IV)-organic complexes in the porewater. Overall, the excess
      organic complexants added did not cause a measurable difference in the solubility
      of Tc(IV) over the control experiments in this organic-rich (12% organic carbon)
      soil. ReO4- did not undergo reduction, as shown by the constant porewater
      concentration and the chromatographic data, and thus Re does notfunction as an
      analogue forTc under environmental nitrate- and iron-reducing conditions.

PMID- 16999128
TI  - Modeling effects of mixtures of endocrine disrupting chemicals at the river
      catchment scale.
AB  - For endocrine disrupting chemicals in the environment, concerns arise primarily
      from the effects that may be induced in wildlife. A well studied example is
      estrogenic chemicals in the aquatic environment and their effects on fish.
      Directly measuring effects, in fieldwork studies, is an expensive and time
      consuming approach that is fraught with many difficulties, ranging from study
      design right through to data analysis and interpretation. An alternative approach
      would be to predict the scale of effect(s) using suitable modeling techniques. We
      have attempted to do this using estrogenic chemicals as an example. We chose this
      group of aquatic pollutants because of the current considerable interest in them
      and the wealth of biological data available on them. Using the established GREAT
      ER hydrological model,we have first predicted the concentrations and then the
      estrogenic effects on fish, of estrone, estradiol, ethinyl estradiol, and
      nonylphenol individually throughout an entire river catchment. We then show that
      knowledge of the biological responses of fish to mixtures of these chemicals can
      be used to predict the effect of environmentally realistic mixtures of them. To
      determine the degree of risk posed by this group of chemicals, it was necessary
      to take into account mixture effects: assessment on a chemical by chemical basis
      led to underestimations of the risk. Finally, we show that the approach can be
      used to predict how the risk will be affected by changes in the concentration of
      one chemical in the mixture. Although we have used only one endpoint
      (vitellogenin induction as an estrogenic response) and one group of similarly
      acting chemicals, we suggest that this general approach could prove extremely
      useful to regulatory authorities and other parties charged with protecting
      aquatic wildlife from adverse effects caused by chemicals in their environment.

PMID- 16999129
TI  - Biological reduction of nanoengineered iron(III) oxide sculptured thin films.
AB  - Sculptured thin films (STFs) are assemblies of nominally identical, parallel
      nanowires with tailored shapes such as chevrons and spirals. A series of
      iron(lll) STFs were produced with varied crystallinity (from hematite
      toferrihydrite) and nanowire shapes (slanted columnar, clockwise helical, and
      counterclockwise helical). When the dissimilatory metal-reducing bacterium
      Shewanella putrefaciens CN32 was used to measure their bioreducibility, it was
      found that bioreduction was controlled primarily by oxide crystallinity. STFs
      were characterized by scanning electron microscopy, atomic force microscopy, and
      grazing incidence small-angle X-ray scattering. Postbioreduction
      characterizations determined that mineralogy of the film materials did not
      change, but surface roughness generally increased. Changes caused by bioreduction
      were assessed in terms of both transmittance and reflectance of light incident
      normal to the STFs. The greatest optical changes were obtained with crystalline
      hematite films. These results underscore the feasibility of an STF-based fiber
      optic iron(lll) reduction sensor for in situ subsurface deployment.

PMID- 16999130
TI  - Donnan membrane approach: from equilibrium to dynamic speciation.
AB  - Metal ion toxicity is not simply related to the total concentration but to the
      free or labile metal ion concentration. One of the techniques that can measure
      the free metal ion concentration is the Donnan Membrane Technique (DMT). However,
      this method has limitations in terms of a relatively high detection limit (in
      relation to typical environmental concentrations) and a long equilibration time.
      We have therefore developed the Flux Donnan Membrane (FDM) Technique, which is a
      dynamic modification of the standard DMT with improved detection limits and a
      more rapid response. We show that experimental calibrations of metal ion
      transport in the FDM can be used to measure [M]free under conditions of either
      solution-controlled or membrane-controlled diffusive transport. The FDM was used
      to measure cobalt binding isotherms by a humic substance over a large range of
      free Co concentrations and pH.

PMID- 16999131
TI  - Chemical and physical properties of ultrafine diesel exhaust particles sampled
      downstream of a catalytic trap.
AB  - The chemical and physical properties of exhaust particles produced by a
      Caterpillar 3176 C-12 heavy duty diesel engine equipped with a catalytic trap
      (CRT) are reported. The engine was operated at 600 Nm and 1500 rpm, using fuels
      containing 15 and 49 ppm sulfur. A two-stage dilution tunnel designed to simulate
      the reactions that occur when hot combustion products mix with cooler atmospheric
      air was used. Particle size distributions were measured using a scanning mobility
      particle sizer (SMPS) and nano-scanning mobility particle sizer (nano SMPS); a
      nanomicro-orifice uniform deposit impactor (nano MOUDI) collected size-resolved
      samples for gravimetric and chemical analysis. A nanometer tandem differential
      mobility analyzer (nano TDMA) was used to measure the volatility and
      hygroscopicity of 4-15 nm particles. These measurements confirm that the
      particles consisted primarily of sulfates.

PMID- 16999132
TI  - Efficient destruction of pathogenic bacteria with NiO/SrBi2O4 under visible light
      irradiation.
AB  - The photocatalytic inactivation of pathogenic bacteria in water was investigated
      systematically with NiO/SrBi2O4 under visible light (lambda > 420 nm)
      irradiation. The catalyst was found to be highly effective in killing Escherichia
      coli, a Gram-negative bacterium, and Staphylococcus aureus, a Gram-positive
      bacterium. ESR studies revealed that *OH and O2*- were involved as the active
      species in the photocatalytic reaction. The decomposition process of the cell
      wall and the cell membrane was directly observed byTEM and further confirmed by
      the determination of potassium ion (K+) leakage from the killed bacteria. A
      possible cell damage mechanism by visible-light-driven NiO/SrBi2O4 is proposed.
      In addition, the effects of pH, methanol, and inorganic ions on bacterial
      photocatalytic inactivation were investigated. These results indicated that the
      electrostatic force interaction of bacteria-catalyst is crucial for high
      bactericidal efficiency.

PMID- 16999133
TI  - Fe(0) nanoparticles for nitrate reduction: stability, reactivity, and
      transformation.
AB  - The pyrophoric character of zerovalent iron nanoparticles and cumbersome handling
      of this material has been a drawback in practical applications, despite the
      expectation of an enhanced reactivity. We have been interested in how the iron
      nanoparticles can gain stability in air without significantly sacrificing
      reactivity. The freshly synthesized iron nanoparticles ignited spontaneously upon
      exposure to air. However, when exposed slowly to air, an approximately 5 nm
      coating of iron oxide was formed on the surface of particles. The oxide shell did
      not thicken for at least two months, indicating no sign of further corrosion of
      iron particles. The reactivity studies on nitrate reduction showed that the
      freshly synthesized iron reacted at the fastest rate. After formation of the
      oxide shell the rate constants decreased by ca. 50% of that of fresh iron, but
      were still higher than that of commercial grade micro- or milli-sized iron
      powder. Nitrate (50 ppm/350 mL) can be recharged 6 times into a bottle containing
      0.5 g of iron nanoparticles. The reduction rate of the second cycle was the
      fastest among the six cycles, which can be attributed to the increase of surface
      area and the fresh iron surfaces that were bared by the dissolution of oxidized
      iron species on the surface. The oxidized iron was transformed to crystalline
      magnetite (Fe3O4) in solution.

PMID- 16999134
TI  - Nickel stabilization efficiency of aluminate and ferrite spinels and their
      leaching behavior.
AB  - Stabilization efficiencies of spinel-based construction ceramics incorporating
      simulated nickel-laden waste sludge were evaluated and the leaching behavior of
      products investigated. To simulate the process of immobilization, nickel oxide
      was mixed alternatively with gamma-alumina, kaolinite, and hematite. These
      tailoring precursors are commonly used to prepare construction ceramics in the
      building industry. After sintering from 600 to 1480 degrees C at 3 h, the nickel
      aluminate spinel (NiAl204) and the nickel ferrite spinel (NiFe204) crystallized
      with the ferrite spinel formation commencing about 200-300 degrees C lower than
      for the aluminate spinel. All the precursors showed high nickel incorporation
      efficiencies when sintered at temperatures greater than 1250 degrees C. Prolonged
      leach tests (up to 26 days) of product phases were carried out using a pH 2.9
      acetic acid solution, and the spinel products were invariably superior to nickel
      oxide for immobilization over longer leaching periods. The leaching behavior of
      NiAl2O4 was consistent with congruent dissolution without significant
      reprecipitation, but for NiFe2O4, ferric hydroxide precipitation was evident. The
      major leaching reaction of sintered kaolinite-based products was the dissolution
      of cristobalite rather than NiAl2O4. This study demonstrated the feasibility of
      transforming nickel-laden sludge into spinel phases with the use of readily
      available and inexpensive ceramic raw materials, and the successful reduction of
      metal mobility under acidic environments.

PMID- 16999135
TI  - Comparative study on the regeneration of flue-gas desulfurizing agents by using
      conventional electrodialysis (ED) and bipolar membrane electrodialysis (BMED).
AB  - Piperazine is an ideal desulfurizing agent but the heat-stable salts formed in
      desulfurization have caused secondary pollution and waste of resources. In the
      previous paper, a method was reported to regenerate piperazine by using BMED. To
      find the variety of that regeneration process, we performed experiments on the
      regeneration of piperazine by using ED. In comparison, ED has higher piperazine
      yield and current efficiency, and much lower voltage drop and energy consumption.
      However, its process cost is higher than that of BMED due to an extra expenditure
      for the base and its tank and pumps. The process cost is estimated to be 0.96
      dollar/kg Pz for BMED and 1.14 dollar/kg Pz for ED. Notably, BMED has more
      environmental benefits and will be more economically attractive as the control on
      secondary pollution is strengthened and the bipolar membrane cost decreases.

PMID- 16999136
TI  - PM0.1 emissions during diesel trap regeneration.
AB  - A nanostructured spinel-type oxide catalyst (CoCr2O4) prepared by solution
      combustion synthesis was developed and deposited over a SiC wall-flow trap for
      diesel particulate removal. Bench tests proved that, after soot loading, the
      developed trap enables a faster and more complete regeneration at 550 degrees C
      than a commercial Pt-catalyst based trap or a noncatalyzed trap. On the other
      hand, secondary nanoparticle emission occurs during the fast regeneration
      promoted by the CoCr2O4-catalyzed trap. This is a likely consequence of oxidative
      fragmentation of the trapped soot agglomerates. This problem can be resolved by
      performing a "mild" regeneration at lower temperatures (e.g., 450 degrees C).

PMID- 16999137
TI  - Changes in solution color during phenol oxidation by Fenton reagent.
AB  - Fenton reaction is a highly effective treatment for degrading phenolic compounds
      in an aqueous solution. However, during phenol oxidation, the oxidized water
      takes on a dark brown color associated with increased toxicity. Then, although
      phenol can be completely removed, if the oxidation process is not carried out
      properly, the final wastewater will be brown in color and have higher toxicity,
      two parameters in which legislation imposes restrictions. This paper analyzes the
      development of the dark color observed in the solution under oxidation treatment
      and formulates a reaction mechanism to explain the color generation. The
      experiments were carried out following the batch-wise procedure, but with the
      solution pH being kept constant throughout the reaction at its optimum value for
      phenol removal, i.e., pH 3.0. It is checked experimentally that color is formed
      at the beginning of the reaction in less than five minutes, and follows the
      kinetic-path of a reaction intermediate. During the first steps of the reaction
      phenol is degraded to dihydroxylated rings (catechol, resorcinol, and
      hydroquinone). These aromatic intermediates generate higher colored compounds
      such as ortho- and parabenzoquinone. On the other hand the dihydroxylated rings
      can react with their own quinones to generate charge-transfer complexes
      (quinhydrone), compounds which take on a dark color at low concentrations.
      Moreover, when iron reacts with hydrogen peroxide, ferric ions are generated that
      can be coordinated to benzene rings to produce colored metal complexes. The
      observed color of the solution is not a fortuitous result depending on trace
      components of low significance, but depends directly on the main reaction
      intermediates, so it is concluded that observed color depends on the level of
      oxidation reached. The maximum color observable during oxidation treatment (A(o))
      depends only on initial phenol concentration and not on oxidant or catalyst
      doses.

PMID- 16999138
TI  - Transport and activity of Desulfitobacterium dichloroeliminans strain DCA1 during
      bioaugmentation of 1,2-DCA-contaminated groundwater.
AB  - The transport and activity of Desulfitobacterium dichloroeliminans strain DCA1 in
      1,2-dichloroethane (1,2-DCA)-contaminated groundwater have been evaluated through
      an in situ bioaugmentation test at an industrial site (Belgium). The migration of
      strain DCA1 was monitored from an injection well toward a monitoring well, and
      the effect of the imposed groundwater flow on its distribution was assessed by
      means of transport model MOCDENS3D. The results of the real-time PCR (16S rRNA
      gene) quantification downstream from the injection point were used to evaluate
      the bacterial distribution pattern simulated by MOCDENS3D. In the injection well,
      the 1,2-DCA concentration in the groundwater decreased from 939.8 to 0.9 microM
      in a 35 day time interval and in the presence of a sodium lactate solution.
      Moreover, analyses from the monitoring well showed that the cells were still
      active after transport through the aquifer, although biodegradation occurred to a
      lesser extent. This study showed that strain DCA1 can be successfully applied for
      the removal of 1,2-DCA under field conditions and that its limited retardation
      offers perspectives for large-scale cleanup processes of industrial sites.

PMID- 16999139
TI  - Saving energy and reducing emissions of both polycyclic aromatic hydrocarbons and
      particulate matter by adding bio-solution to emulsified diesel.
AB  - Development of emulsified diesel has been driven by the need to reduce emissions
      from diesel engines and to save energy. Emulsification technology and bio
      solution (NOE-7F) were used to produce emulsified diesel in this study. The
      experimental results indicated that there were no significant separation layers
      in W13 (13 wt % water + 87 wt % PDF), W16 (16 wt % water + 84 wt % PDF), W19 (19
      wt % water + 81 wt % PDF), E13 (13 wt % NOE-7F water + 87 wt % PDF), E16 (16 wt %
      NOE-7F water + 83 wt % PDF), and E19 (19 wt % NOE-7F water + 81 wt % PDF) after
      premium diesel fuel (PDF) was emulsified for more than 30 days. In addition,
      there was no significant increase in damage from using these six emulsified fuels
      after the operation of the diesel generator for more than one year. The energy
      saving and reduction of particulate matter (PM) and total polycyclic aromatic
      hydrocarbons (PAHs) for W13, W16, W19, E13, E16 and E19, respectively, were
      3.90%, 30.9%, 27.6%; 3.38%, 37.0%, 34.9%; 2.17%, 22.2%, 15.4%; 5.87%, 38.6%,
      49.3%; 5.88%, 57.8%, 58.0%; and 4.75%, 31.1%, 47.3%, compared with PDF. The above
      results revealed that the bio-solution (NOE-7F) had a catalytic effect which
      elevated the combustion efficiency and decreased pollutant emissions during the
      combustion process. Furthermore, bio-solution (NOE-7F) can stabilize the
      emulsified fuels and enhance energy saving. Thus, emulsified fuels are highly
      suitable for use as alternative fuels. Due to the increasing price of diesel,
      emulsified diesel containing NOE-7F has potential for commercial application.

PMID- 16999140
TI  - Direct volatilization of naphthalene to the atmosphere at a phytoremediation
      site.
AB  - Phytoremediation systems are known to reduce groundwater contamination by at
      least three major mechanisms: plant uptake, phytovolatilization, and enhanced
      rhizosphere bioremediation. The potential for such systems to enhance a fourth
      remediation pathway--direct surface volatilization of contaminants through the
      subsurface and into the atmosphere-has not yet been investigated in the field. A
      vertical flux chamber was used to measure direct surface volatilization of
      naphthalene over nine months at a creosote-contaminated site in Oneida,
      Tennessee, where a phytoremediation system of poplar trees was installed in 1997.
      A maximum flux of 23 microg m(-2) h(-1) was measured in August 2004, and
      naphthalene removal by the direct volatilization pathway is estimated to be 50 g
      yr(-1) at this site. Results suggest that direct volatilization fluxes are most
      strongly affected by the groundwater level (thickness of the saturated zone),
      soil moisture, and changes in atmospheric pressure. At this site, transpiration
      and canopy interception resulting from the phytoremediation system significantly
      reduce the saturated thickness, increasing the vertical concentration gradient of
      naphthalene in the groundwater and thus increasing the upward diffusive flux of
      naphthalene through the subsurface. The presence of the trees, therefore,
      promotes direct volatilization into the atmosphere. This research represents the
      first known measurement of naphthalene attenuation by the direct volatilization
      pathway.

PMID- 16999141
TI  - Arsenic removal from groundwater by household sand filters: comparative field
      study, model calculations, and health benefits.
AB  - Arsenic removal efficiencies of 43 household sand filters were studied in rural
      areas of the Red River Delta in Vietnam. Simultaneously, raw groundwater from the
      same households and additional 31 tubewells was sampled to investigate arsenic
      coprecipitation with hydrous ferric iron from solution, i.e., without contact to
      sand surfaces. From the groundwaters containing 10-382 microg/L As, < 0.1-48 mg/L
      Fe, < 0.01-3.7 mg/L P, and 0.05-3.3 mg/L Mn, similar average removal rates of 80%
      and 76% were found for the sand filter and coprecipitation experiments,
      respectively. The filtering process requires only a few minutes. Removal
      efficiencies of Fe, phosphate, and Mn were > 99%, 90%, and 71%, respectively. The
      concentration of dissolved iron in groundwater was the decisive factor for the
      removal of arsenic. Residual arsenic levels below 50 microg/L were achieved by
      90% of the studied sand filters, and 40% were even below 10 microg/L. Fe/As
      ratios of > or = 50 or > or = 250 were required to ensure arsenic removal to
      levels below 50 or 10 microg/L, respectively. Phosphate concentrations > 2.5 mg
      P/L slightly hampered the sand filter and coprecipitation efficiencies.
      Interestingly, the overall arsenic elimination was higher than predicted from
      model calculations based on sorption constants determined from coprecipitation
      experiments with artificial groundwater. This observation is assumed to result
      from As(lll) oxidation involving Mn, microorganisms, and possibly dissolved
      organic matter present in the natural groundwaters. Clear evidence of lowered
      arsenic burden for people consuming sand-filtered water is demonstrated from hair
      analyses. The investigated sand filters proved to operate fast and robust for a
      broad range of groundwater composition and are thus also a viable option for
      mitigation in other arsenic affected regions. An estimation conducted for
      Bangladesh indicates that a median residual level of 25 microg/L arsenic could be
      reached in 84% of the polluted groundwater. The easily observable removal of iron
      from the pumped water makes the effect of a sand filter immediately recognizable
      even to people who are not aware of the arsenic problem.

PMID- 16999142
TI  - Fuel oxidation efficiencies and exhaust composition in solid oxide fuel cells.
AB  - Solid oxide fuel cells (SOFCs) are electrochemical devices that rely on ion
      migration through a solid-state electrolyte to oxidize fuel and produce
      electricity. The present study employs Fourier transform infrared spectroscopy to
      quantify the exhaust of an SOFC operating with fuel flows of methane over Ni/YSZ
      cermet anodes and butane over Ni/YSZ and Cu/CeO2/YSZ cermet anodes. Data show
      that hydrocarbon fuels can participate in a variety of different reactions
      including direct electrochemical oxidation, various reforming processes, and
      surface-catalyzed carbon deposition. These findings have direct consequences for
      assessing the environmental impact of SOFCs in terms of the exhaust discharged
      from devices operating with common hydrocarbon fuel feeds. In the work presented
      below, a measure of fuel oxidation efficiency is found by comparing the partial
      pressure of CO2 (P(CO2)) in the SOFC exhaust to the partial pressure of CO
      (P(CO)). The fuel anode combination with the largest P(CO2)/P(CO) ratio is the
      C4H10 over Cu/CeO2 combination (0.628 +/- 0.016). The CH4 over Ni cell type has
      the second highest ratio (0.486 +/- 0.023). The C4H10 over Ni cell type gives a
      ratio of 0.224 +/- 0.001. Attempts to balance the carbon content of the fuel feed
      and exhaust lead to predictions of SOFC fuel oxidation mechanisms.

PMID- 16999143
TI  - New perspectives on perfluorochemical ecotoxicology: inhibition and induction of
      an efflux transporter in the marine mussel, Mytilus californianus.
AB  - The toxicological effects of perfluoroalkyl acids on the p-glycoprotein (p-gp)
      cellular efflux transporter were investigated using the marine mussel Mytilus
      californianus as a model system. Four of the perfluoroalkyl acids studied exhibit
      chemosensitizing behavior, significantly inhibiting p-gp transporter activity.
      The inhibitory potency is maximal for the longer chain acids perfluorononanoate
      (PFNA) and perfluorodecanoate (PFDA), with average IC50 values of 4.8 and 7.1
      microM, respectively. Results indicate that PFNA inhibits p-gp by an indirect
      mechanism, and this inhibition is reversible and accompanied by a rapid loss of
      PFNA from the tissue. In addition, PFNA induces expression of the p-gp
      transporter after a 2-h exposure, a stress response that may result in a
      metabolic cost to the organism. Given that most organisms, including humans,
      share efflux transporters as a first line of defense against toxicants, the
      results of this study may have broader implications for the ecotoxicology of
      perfluoroalkyl acids.

PMID- 16999144
TI  - Is there still a role for experimental surgery in the surgical sciences?
AB  - The firm opposition of public opinion and the reduction in public funding have
      remarkably curtailed the role of experimental surgery which several years ago was
      a key aspect of the activity of a surgical department. Experimental surgery in
      large animals has been virtually banned and experimental research in small
      animals requires the use of complex microsurgical techniques. In our opinion,
      experimental surgery is still useful in order to test new surgical devices and
      new drugs, especially in the field of transplant surgery. Another important
      function of experimental surgery is to facilitate the training of surgical
      residents in order to speed up the process of acquiring experience and expertise.
      Public opinion can be reassured because the legislation is very strict and
      safeguards the well-being of animals.

PMID- 16999145
TI  - Intraoperative identification and effective "blood patch" prevention of
      persistent air leak in lung resections.
AB  - Persistent air leak (PAL) is the most common complication after lung resection,
      requiring additional treatments and hospital stay. Intraoperative prevention of
      PAL is usually left to the surgeon's subjective judgement, with inconsistent
      results. The aim of the study was to establish systematic, reproducible
      quantification of air leaks at thoracotomy in order to identify those which are
      potentially persistent, to be preventively treated by intraoperative "blood
      patch" pneumo-stasis. In a consecutive series of 570 lung resections, parenchymal
      suture air tightness was tested intraoperatively at end-inspiratory pressure
      intervals from 15 to 35 cm H2O. Air leaks at 15 cm H2O (n=40) were considered too
      critical, while air escape beyond 30 cm H2O (n=437) was deemed quickly self
      sealing postoperatively; these conditions were managed by further surgery and
      standard chest tubes only, respectively. Air leaks between 16 and 30 cm H20
      (n=93) were assumed to be the main source of postoperative PAL and were
      preventively treated with 50 cc of blood left in the cavity for 3 hours after
      closing the thoracotomy. Chest tubes were set up so as to avoid tension
      pneumothorax or occult bleeding. No early or late major complications were
      related to the intraoperative "blood patch" procedure. The cumulative incidence
      of PAL was 1.4%, most of which (6/8) belonging to the group leaking air in the 16
      30 cm H2O pressure interval. In contrast, the PAL rate in the 437 patients
      reputed to be at low risk was 0.2%. The overall mean hospital stay was 7.2 days,
      the mean duration of chest tube duration 3.5 days, and the complication rate 15%.
      According to our retrospective data, air leaks occurring between 16 and 30 cm H2O
      of pressure in the intubated lung were identified as carrying the highest risk of
      becoming persistent postoperatively; intraoperative "blood patch" pneumo-stasis
      is a convenient and successful preventive method to minimize PAL occurrence in
      this group of patients.

PMID- 16999146
TI  - [Maximum gastric cancer diameter: prognostic factor or important clinical
      feature?].
AB  - Maximum tumor diameter (DMAX) is considered by many Authors as an im prognostic
      factor in gastric cancer (GC) correlated with tumor depth (pT). Aim of this
      retrospective study was to evaluate the prognostic value of DMAX and its
      predictive role of tumor stage in a series of 164 gastric cancer patients. One
      hundred and sixty-four patients underwent gastrectomy between January 1994 and
      December 2004. DMAX value was measured on resected specimens fixed in 10%
      formalin solution with cut-off of 40 mm. Tumors according to these measurements
      were classified in DMAX1 < or = mm and DMAX2 >40 mm. The prognostic significance
      of DMAX along with other factors was evaluated with log-rank test and Cox
      regression. The correlation between DMAX and other variables was calculated by
      Spearman test. Overall 5-year survival rate is 56.6%. DMAX resulted significantly
      linked to survival at univariate analysis (p = 0.0001). The Spearman correlation
      test showed that DMAX is strongly correlated with tumor stage (positive
      predictive value of 88.5%), pT, pN, residual of tumor and grading. Our results
      showed that patients with large tumor at an increased risk for tumor advancement
      and, therefore, DMAX could represent a useful parameter for selection of patients
      for neoadjuvant protocols.

PMID- 16999147
TI  - [Multimodal treatment in locally advanced esophageal cancer: a multicenter phase
      II study with neoadjuvant oxaliplatin, 5-fluorouracil, leucovorin and neoadjuvant
      radiotherapy: preliminary results].
AB  - The aim of the study was to evaluate the feasibility and efficacy of treatment
      with oxaliplatin, 5-fluorouracil and leucovorin concomitant with radiation
      therapy in locally advanced oesophageal cancer. Fifty-eight patients with
      previously untreated, histologically proven oesophageal cancer were enrolled.
      Downstaged patients underwent either surgery or received brachytherapy. We report
      the results obtained in the first 54 patients. The median age was 58 years. The
      diagnosis was squamous cell carcinoma/adenocarcinoma/poorly differentiated:
      45/8/1; clinical stage: T3N1M0 38 (70%), T4 10 (19%), M1a 6 (11%). Thirty-nine
      patients (72%) received the planned 8 weeks of chemotherapy and 45 completed the
      entire course of scheduled radiotherapy. Four (7%) toxic deaths were recorded, 2
      more patients died prematurely from massive oesophageal bleeding and 1 from
      progression of disease. We recorded 8 (15%) complete responses and 24 (44%)
      partial responses. Resection was complete (R0) in 24 (80% of resected patients,
      44% of treated patients). A complete pathological response was documented in 6
      patients (11% of those treated). Postoperative complications were recorded in 8
      (25%) patients, with 2 (6.2%) deaths. RO resection was accomplished in 44% of
      patients. Toxicity was moderate, but postoperative mortality was not negligible.
      Survival data are awaited before a phase III comparison with cisplatin-containing
      chemo-radiotherapy may be considered.

PMID- 16999148
TI  - [Incidental thyroid microcarcinoma in benign thyroid disease. Incidence in a
      total of 100 consecutive thyroidectomies].
AB  - Over the past few years, incidental thyroid microcarcinoma has become a frequent
      disease and its incidence in some reports is considerable. Discovering new cases
      depends on the extended indications for total thyroidectomy for benign disease,
      on progress in the field of diagnostic instruments (ultrasound, scintigram, fine
      needle biopsy for cytology, CT scan, MRI), and on the pathology examination of
      very thin slices of specimens. In spite of the high incidence reported in some
      autopsy series, suggesting that this tumour may have a good prognosis, some
      Authors report an overall incidence of up to 11% of local recurrence, metastasis
      or mortality. For all these reasons the surgical treatment of incidental thyroid
      microcarcinoma is still controversial. The aim of this study was to estimate the
      incidence and examine the clinical-pathological findings of incidental thyroid
      microcarcinoma in a series of 100 consecutive thyroidectomies and to evaluate
      whether complete removal of the gland should be adopted in all cases. In the
      present series the incidence of incidental thyroid microcarcinoma was 21.6%
      (19/88). Total thyroidectomy was considered the treatment of choice for diffuse
      benign disease and appeared to be necessary for both the diagnosis and treatment
      of incidental thyroid microcarcinoma.

PMID- 16999149
TI  - [Small bowel obstruction caused by postoperative adhesions: personal experience
      and review of the literature].
AB  - Small bowel obstruction due to postoperative adhesions still remains an important
      matter in terms of frequency, diagnostic and therapeutic commitment and costs.
      The Authors report on a series observed over 14 years consisting of 63 patients
      (71 cumulative hospital admissions). Surgery was required in 42 cases (59.2%), 23
      cases were treated in emergency and 19 cases after failure of conservative
      treatment. In 29 cases (69%) the surgical procedure was limited to adhesiolysis,
      whereas in 13 cases (31%) an intestinal resection was performed. During operation
      the mechanisms responsible for obstruction were: strangulation by an adhesive
      band (39.4%), angulation (34%), bowel loops and volvulus glued together (13.2% in
      each case). The operative mortality was 4.7% (2 cases). In 29 cases (40.8%),
      after medical treatment, the obstruction was completely resolved within a mean
      period of 4.15 days (range: 2-8). The results lead to the conclusion that
      diagnostic accuracy in cases of obstruction due to postoperative adhesions is
      still uncertain. The main aspects of treatment and surgical timing are left to
      the surgeon's personal experience. Medical treatment, however, should be the
      first therapeutic option and, in case of doubt, further diagnostic investigations
      are necessary (mainly CT) to identify those cases amenable to surgical treatment.

PMID- 16999150
TI  - [Diagnostic-therapeutic pathways as instruments of clinical management:
      experience at the S. Maria Hospital in Terni].
AB  - Diagnostic-therapeutic itineraries and treatment profiles are instruments of
      clinical management. The authors report on their experience with the experimental
      creation of such itineraries in thyroid nodular pathology. These are the fruit of
      collaboration between the management team, endocrinological surgeons, and the
      hospital computer staff. The drawing-up of guidelines in the hospital setting
      allows the systematic organisation of clinical activities to be accomplished in
      the health-care facility, quantifying costs for all diseases in order to be able
      to plan and implement changes in resources and staff utilisation. Application of
      the method, in addition, helps to develop a common language among hospital
      doctors and nurses, facilitates proper communication with patients, and ensures
      adequate patient information regarding the clinical itinerary the patient will
      have to take for his or her condition.

PMID- 16999151
TI  - [Management of infected vascular grafts. Are there any factors predictive of
      early clinical success?].
AB  - The aim of the study was to define mortality and limb loss rates and to identify
      factors predictive of early clinical success in the management of infected
      vascular grafts. Clinical data of 40 patients were reviewed, evaluating
      comorbidity factors, laboratory findings, ischaemic symptoms, graft material and
      time of onset of infections. Diabetes and chronic renal insufficiency were
      reported in 15% of cases, malignancy in 10%, pathological C-reactive protein in
      77.5% and leukocytosis in 60%. 52.5% of the patients presented with a disabling
      claudication, and 77.5% with an infected alloplastic graft. Early infection had
      developed in 57.5%. A total graft excision was performed in 72.5% of cases. Early
      complications were recorded in 32.5% of the patients, with a limb loss rate of
      22.5% and a mortality rate of 10%. Total graft excision is the treatment of first
      choice in patients with an infected vascular graft. Patients presenting with
      critical ischaemia and early septic complications will experience poor clinical
      results in terms of limb loss and mortality. Pathological blood levels of C
      reactive protein could help in the choice of treatment in unclear cases.

PMID- 16999152
TI  - [Empiric antibiotic therapy in the treatment of postoperative abdominal
      abscesses. Clinical and microbiological data].
AB  - Abdominal abscesses arising postoperatively constitute a serious problem,
      particularly in the field of oncological surgery. The aim of our study was to
      interpret clinical and microbiological data relating to a population of
      oncological patients, undergoing ultrasound-guided drainage for postoperative
      abdominal abscesses, so as to be able to better plan empiric antibiotic therapy.
      We therefore retrospectively analysed the data of 24 patients operated on for
      neoplastic pathologies and treated with ultrasound-guided percutaneous drainage
      for abdominal abscesses during the postoperative period. Microbiological and
      clinical data showed that abscesses located in the lower abdominal regions almost
      always present a polymicrobial growth, though abscesses in the upper regions are
      more frequent. Moreover, the antibiotic assay results prompted us to consider the
      use of beta-lactamines, quinolones and glycopeptides more favourably, in view of
      their greater efficacy against the microbes tested. Thus, the planning of empiric
      antibiotic therapy should be based above all on the anatomical-topographic
      location of the abdominal abscess and on the type of operation performed, with
      thorough assessment of the use of the above-mentioned antibiotics.

PMID- 16999153
TI  - [Laparoscopy in traumatic abdominal emergencies].
AB  - Over the past few years the laparoscopic technique has changed most of the
      concepts of traditional surgery and is today the standard approach in elective
      surgery for many pathologies requiring surgery. Unfortunately the same cannot be
      said for emergency surgery, though much progress has been made in this field,
      too. The Authors examine the most important abdominal diseases that can be
      diagnosed and, possibly, treated by the laparoscopic approach in the emergency
      setting, concluding that laparoscopic management of such conditions is a feasible
      proposition in many cases. Technological improvements and the development of new,
      more versatile surgical instruments will undoubtedly contribute to the
      increasingly widespread use of the laparoscopic approach also in emergency
      procedures.

PMID- 16999154
TI  - [Fecal incontinence: role of anal sphincter rehabilitation].
AB  - Fecal incontinence is a highly disabling symptom which causes the patient to
      gradually abandon all forms of social, family and working relationships.
      Rehabilitation was adopted initially in cases of surgical failure and considered
      as being only palliative. In our study we tested an original rehabilitation
      protocol for faecal incontinence which embraces 3 methods--physio-kinesitherapy,
      electrostimulation and biofeedback--in what we have called "anal sphincter
      functional rehabilitation". The study was conducted in 196 patients (61 M, 135 F)
      mean age 42.9 (range: 11-86), with faecal incontinence of varying aetiology. The
      3 methods were carried out simultaneously in 3 one-hour sessions a week. The
      protocol envisaged 15 consecutive sessions at the end of which a first assessment
      was made of the results achieved. Therapeutic success was achieved in 93.4% of
      cases. The results obtained with our protocol do not differ from those reported
      by other Authors and we can therefore state that functional rehabilitation of the
      anal sphincter is to be viewed not merely as a valid alternative to surgery, but
      as the therapy of choice for fecal incontinence.

PMID- 16999155
TI  - [Partial left lateral subcutaneous sphincterotomy for anal fissure: role and
      results].
AB  - This is a retrospective analysis of the results obtained with surgical treatment
      consisting in left lateral partial subcutaneous sphincterotomy for anal fissure.
      Fifty patients observed from January 2002 to June 2005 in our Coloproctology
      outpatients' department were recruited. Five patients (10%) did not undergo an
      operation and all 5 presented an acute anal fissure. Their treatment was
      conservative consisting in fibre ingestion, use of stool softeners, ointments,
      anti-inflammatory agents after opening the bowel, and a corticosteroid ointment.
      Forty-five patients (90%) were operated on. Twelve of these (26%) were operated
      on for an acute anal fissure after early failure of conservative therapy and
      demanded immediate surgical therapy; 14 (31%) of those operated on for acute anal
      fissure underwent a surgical procedure after at least a month of conservative
      treatment. The remaining 19 patients (42%) presented chronic anal fissures, with
      symptoms lasting more than 1 month and with sentinel haemorrhage, a hypertrophied
      anal papilla, and hardening of the edge of the fissures. Forty of the patients
      operated on (88%) presented a posterior anal fissure, 3 patients (6.5%) an
      anterior anal fissure and 2 patients (4.5%) synchronous anterior and posterior
      anal fissures. The surgical procedure carried out on all patients undergoing
      operation was a partial left lateral subcutaneous internal sphincterotomy using
      the closed technique according to Notoras under general anaesthesia. Follow-up
      was carried out 15 days and 2, 3 and 6 months postoperatively. The results were
      considered very good in 89% of the cases, while 5 patients (11%) complained of
      pain after opening the bowels, albeit of acceptable intensity and such as not to
      require another operation or significant pharmacological treatment. No
      complications were observed. The conclusion after the analysis of our experience
      is in agreement with the 8th recommendation, class I, recommendation grade A of
      the "The Standards Practice Task Force of the American Society of Colon and
      Rectal Surgeons" stating that "surgery may be appropriately offered without a
      trial of pharmacologic treatment after failure of conservative therapy" and that
      "in our experience can be proposed in those cases of acute anal fissure". In our
      experience, the 89% success rate and substantial patient satisfaction make this
      procedure more appropriate than medical treatment and alternative surgical
      treatments.

PMID- 16999156
TI  - [The Keel Mesh prosthesis: an innovative surgical device for a modern Bassini
      inguino-crural hernia operation without limits].
AB  - Accepting the therapeutic rational underlying laparoscopic and suprapubic
      laparotomy access, the same therapeutic goal is achieved through direct inguinal
      access. In this way, using just one prosthesis, inguinal-crural hernias of the
      Fruchaud pectineus orifice can be treated. The patented three-dimensional pre-cut
      Keel Mesh prosthesis made of polypropylene monofilament interwoven in a mesh, is
      tension-free and endowed with plastic memory. It is applied using a slightly
      modified Lichtenstein technique and is composed of two assembled elements (A and
      B-C) of different shapes and sizes. From May 2000 to December 2005, the Keel Mesh
      prosthesis was used in 358 surgical inguino-crural alloplasty operations
      according to Lichtenstein-De Pascale in 328 patients. Thirty patients were
      treated with bilateral allo-plasties. Coexistence of a crural hernia was found in
      13 male and 4 female patients (5%). At the present time all the patients who are
      entering into follow-up at different times show perfect compliance of the
      prosthesis with no relapses. The theoretical and practical considerations
      regarding the production of the Keel Mesh prosthesis and its easy application
      suggest it is an extremely valid, rational device for the initial and combined
      treatment of inguinal and crural hernia.

PMID- 16999157
TI  - A case of T-tube dislocation.
AB  - In environments where endoscopic retrograde cholangio-pancreatogram (ERCP)
      services may at time be limited or unavailable, the surgeon must also decide
      between the insertion of a conventional T-tube or primary choledochorrhaphy when
      it is operatively perceived that the common bile duct (CBD) has been adequately
      cleared. Where the hospital stay of the patients with a T-tube in situ is
      prolonged, there is a higher incidence of postoperative bacteraemia with a
      moderate morbidity from biliary leakage after T-tube withdrawal. We report here a
      case as well as methods designed to prevent tube dislocation and alternatives to
      T-tube insertion after choledochotomy, whether performed open or
      laparoscopically.

PMID- 16999158
TI  - [Ileal leiomyosarcoma presenting with an episode of acute massive intestinal
      bleeding].
AB  - The aim of this article was to present a case of gastrointestinal stromal tumour
      (GIST) presenting with acute intestinal bleeding. The Authors outline the
      histogenetic, clinical, diagnostic and prognostic profile of this pathology.
      Technical progress in immuno-histochemical and ultrastructural diagnostics has
      made possible to go beyond the old definition of gastrointestinal stromal tumours
      and identify several subgroups of such tumours on the basis of nervous and/or
      muscular phenotypic differentiation. The histopathological and structural variety
      of GIST accounts for their different clinical manifestations and variable and
      unpredictable biological behaviour. Histological criteria are by no means of
      absolute value: tumours considered benign on the basis of histology may present a
      malignant behaviour in the course of time, with the development of metastases and
      recurrences. In this regard, a number of predictive malignancy indices have been
      identified such as the patient's age, tumour size, presence of haemorrhage and
      necrotic areas, high mitotic index (> 5 mitoses/50 HFP), and kit-gene mutations.
      The Authors stress the diagnostic importance of 99m Tc-RBC scintigraphy in the
      case reported and agree with the literature as to the appropriate therapy,
      consisting in intestinal resection. The therapy of active GIST is essentially
      surgical and consists in resection of the intestinal tract affected by the
      tumour: lymphadenectomy must be performed only in case of need, because GIST
      metastasis preferably via the blood stream. As far as therapy is concerned, the
      demonstration of kit-gene mutation, expressed by the more aggressive forms, has
      made it possible to produce an inhibitor of protein tyrosine kinase Ber-Abl,
      which causes selective inhibition of cellular proliferation both in vitro and in
      vivo and induces apoptosis of Ber-Abl positive cell lines.

PMID- 16999159
TI  - A rare case of Bouveret's syndrome presenting with upper gastrointestinal
      bleeding.
AB  - We report a case of duodenal obstruction caused by a large gallstone wedged in
      the duodenal bulb (Bouveret's syndrome), presenting with acute upper
      gastrointestinal bleeding and successfully treated by surgery following a failed
      attempt at endoscopic retrieval of the stone. Haemorrhage is a very rare form of
      presentation. After an extensive review of the literature, the therapeutic
      options and surgical strategies (one-stage and two-stage procedure) are
      critically discussed.

PMID- 16999160
TI  - [Neuroendocrine tumors. A rare case of duodenal carcinoids].
AB  - The authors report their experience with a case of double duodenum carcinoid
      tumors occurring in a 59-year-old female patient. She presented with a one-year
      history of frequent abdominal painful episodes, associated with dyspepsia,
      emesis, pyrosis, eructation, skin flushing and easy strain. The laboratory
      examinations point out high hematic values of serotonin and gastrin, with a
      raising of urinary 5-HIAA. Preoperative endoscopic examinations showed the
      presence of 2 little sessile polypoid growths, placed in the duodenal bulb, one
      of this interested muscular tunic. The patient underwent Billroth I resection and
      was discharged on postoperative day 8. The authors after a little dissertation on
      that topic, go on to examine the current diagnostic and therapeutic
      possibilities. They confirm the elective role of surgical treatment of these rare
      tumors.

PMID- 16999162
TI  - Validity: from start-up to seasoned. Re-evaluate your practice to win over
      patients and earn new referrals.

PMID- 16999161
TI  - Giant recurrent fibromatosis of the breast: a case report. Clinical features and
      implications for treatment.
AB  - Fibromatosis of the breast is a benign but locally aggressive neoplasm, which has
      been described under various names including extra-abdominal desmoid tumour and
      aggressive fibromatosis. It is a rare condition, accounting for approximately
      0.2% of all solid tumours of the breast. Clinically and radiologically the lesion
      mimics breast cancer and the definitive diagnosis is provided by histology. A
      high risk of local recurrence is a characteristic of this disease. Radical
      excision of the tumour with clear histological margins decreases the likelihood
      of recurrence. The possible association between breast implants and mammary
      fibromatosis has been reported. In this study we report a case of giant
      fibromatosis of the breast observed in a young patient and its extensive
      recurrence, involving all quadrants of the breast, the pectoralis major muscle,
      the rectus abdominis muscle sheath and the costal layer. The main clinical and
      pathological characteristics of this rare disease are illustrated, emphasizing
      the difficulties encountered both in the diagnosis of the primary lesion and in
      the management of its giant recurrence, particularly as regards the possibility
      of obtaining a radical surgical excision and the option of performing breast
      reconstruction.

PMID- 16999163
TI  - The extreme cleaning makeover in dentistry. Interview by Lynne H Slim.

PMID- 16999164
TI  - Current status of tooth whitening: literature review.

PMID- 16999165
TI  - Rationale for the utilization of bonded nonmetal onlays as an alternative to PFM
      crowns.

PMID- 16999166
TI  - Antimicrobial host response therapy in periodontics: a modern way to manage
      disease.

PMID- 16999167
TI  - CAD/CAM use in the dental laboratory.

PMID- 16999168
TI  - Use of a self-etch, self-adhesive resin cement: clinical technique.

PMID- 16999169
TI  - The maxillary anterior/posterior curve of occlusion.

PMID- 16999171
TI  - My endodontic cookbook is lost: Michelangelo versus painting by numbers.

PMID- 16999170
TI  - The use of an antibacterial self-etching bonding agent in routine composite resin
      placement.

PMID- 16999172
TI  - Dread-free compound impressions in half the time.

PMID- 16999173
TI  - Snap-on smile: clinical applications.

PMID- 16999174
TI  - Minimal prep, minimal fuss: direct composite bonding.

PMID- 16999175
TI  - Aphthous ulcers: treatment and case report.

PMID- 16999176
TI  - Secrets to finding and keeping good staff.

PMID- 16999177
TI  - Implementing technology to its fullest advantage.

PMID- 16999178
TI  - Staff nurses as clinical leaders.

PMID- 16999179
TI  - Salute to American nurses.

PMID- 16999180
TI  - Basics of ostomy care.
AB  - Teaching the patient how to care for a new ostomy can be a challenging experience
      for the nurse. The patient with an ostomy needs encouragement, support, and
      counseling to learn how to integrate self-ostomy care into daily activities.
      Collaboratively, the WOCN and medical-surgical nurse can provide the patient and
      his or her family with a more comprehensive approach to ostomy teaching.

PMID- 16999181
TI  - A learning needs assessment of patients with COPD.

PMID- 16999182
TI  - How far do nurses walk?

PMID- 16999183
TI  - Care of the dying: a positive nursing student experience.

PMID- 16999184
TI  - Program for recovering nurses: an evaluation.

PMID- 16999185
TI  - An overview of lung cancer symptoms, pathophysiology, and treatment.

PMID- 16999186
TI  - Managing the pregnant employee.

PMID- 16999187
TI  - Update on depression and antidepressant medications.

PMID- 16999188
TI  - So, what do I put on this wound? Making sense of the wound dressing puzzle: part
      III.

PMID- 16999190
TI  - Prevention of breast cancer in African women.

PMID- 16999191
TI  - Estrogen metabolism and breast cancer risk--a review.
AB  - The standard paradigm providing a general mechanistic explanation for the
      association of cumulative, excessive estrogen exposure and breast cancer risk is
      that estrogen and perhaps progesterone affect the rate of cell division; and thus
      manifest their effect on the risk of breast cancer by causing proliferation of
      breast epithelial cells. Proliferating cells are susceptible to genetic errors
      during DNA replication which, if uncorrected, can ultimately lead to a malignant
      phenotype. This standard paradigm has recently been expanded to encompass
      emerging research data supporting a complementary genotoxic pathway mediated by
      the generation and redox cycling of reactive oxygen species through the metabolic
      effects of estrogen metabolites such 4- and 16a-hydroxy catechols. This paradigm
      shift is necessitated by evidence of estrogen-induced carcinogenesis in several
      animal and human models following exposure to these estrogen metabolites. This
      review examines some of the available evidence relating these estrogen
      metabolites to animal and human breast carcinogenesis.

PMID- 16999192
TI  - Poor pregnancy outcomes among adolescents in South Nyanza region of Kenya.
AB  - In this paper, we examine factors associated with poor pregnancy outcomes among
      teenagers in South Nyanza region of Kenya. The analysis is based on a recent WHO
      funded study on Adolescent safe motherhood in the region, which involved a survey
      of 1247 adolescents aged 12-19 and in-depth interviews with 39 of the adolescents
      who had experienced very early pregnancies or a pregnancy wastage. The indicators
      of poor pregnancy outcomes analysed include pregnancy wastage and pre-term
      delivery. A striking finding is the unusually high rate of pre-term deliveries,
      especially in cases of unintended pregnancies. Analysis of the qualitative data
      based on in-depth interviews sheds some light on possible explanations for the
      poor pregnancy outcomes observed among these adolescents. In particular, unsafe
      abortion attempts and poor maternal health-care emerge as important issues of
      concern.

PMID- 16999193
TI  - Attitude of health-care workers to HIV/AIDS.
AB  - The current 5% prevalence rate of HIV in Nigeria represents a significant
      population of people living with HIV/AIDS (PLWHA). Discrimination against PLWHA
      has profound impact on the care and support required for their optimal management
      particularly in resource-constrained settings. The study sought to assess the
      knowledge of health-care providers about HIV/AIDS, determine the potential for
      discrimination in the provision of services based on patients' HIV sero-status
      and review the factors that may contribute to such attitude. Self-administered
      semi-structured questionnaires were administered to respondents who were selected
      by multi-stage sampling technique. The questionnaires explored the respondents'
      knowledge about HIV and their attitude and practice regarding PLWHA. Three
      hundred and forty-five questionnaires were completed. Only 77.1% correctly
      identified breastfeeding as a source of HIV transmission; 5.2%and 2.6%
      respectively thought transmission was possible through mosquito bite and
      handshake. About 10% and 15% respectively among trained nurses and auxiliary
      nurses were unaware that HIV could be transmitted to the child during delivery.
      Some 13.9% and 12.7% of respondents respectively were unwilling to take vital
      signs and carry out physical examination on PLWHA. Compared to physicians,
      trained nurses and auxiliary nurses were more likely to deny services based on
      HIV sero-status. Negative attitude was more likely if the source of the HIV
      infection was from homosexual exposure or bisexual indiscretion. The health-care
      workers studied manifested certain attitudes that are potentially discriminatory
      of PLWHA. Well-coordinated continuing education of HIV/AIDS for all categories of
      health-care workers is recommended as a vital strategy in the crusade against the
      epidemic.

PMID- 16999194
TI  - The challenge of improving perinatal care in settings with limited resources.
      Observations of midwifery practices in Mozambique.
AB  - The aim of this study was to observe and analyse midwifery care routines related
      to asphyxia and hypothermia during the perinatal period and to investigate the
      effect of an in-service education program. A direct non-participant pre- and post
      intervention observation study of midwifery a performance during childbirth was
      conducted at a labour ward in Maputo. The observed groups consisted of 702 and
      616 midwifery-attended deliveries. Examination was also conducted of the
      partographs (702 vs. 616). The quality of midwifery care related to prevention
      and early detection of asphyxia and hypothermia was found to be inadequate and
      the intervention had no significant effect upon the midwives' performances. This
      could be attributed to the quality of the intervention itself or to failure of
      implementing managerial decisions such as transfer of partograph documentation
      from obstetricians to midwives. Change in professional performance does not
      automatically follow awareness of evidence-based midwifery practices, but
      requires behavioural change, which may be more difficult to achieve.

PMID- 16999195
TI  - Comparative study of the characteristics of family planning service users and non
      users in northwest Ethiopia.
AB  - Three hundred and forty-four (49.6%) family planning users and 350 (50.4%) non
      family planning users were included in a study to assess the factors that are
      associated with utilisation of family planning services at different levels of
      health institutions in northwest Ethiopia. Desire for (more) children was the
      most common reason (51.4%) for not using family planning services, followed by
      inadequate knowledge about family planning services (14.6%). A higher proportion
      of the non-users were illiterate, of lower parity, and had their last child under
      one year of age (P<0.05). In logistics regression analysis family planning was
      significantly lower in the illiterate. Positive husband's attitude had the
      strongest association (OR 9.3, 95% CI 4.6, 18.7) with family planning. In
      addition to programs that create demand for smaller well-spaced children, IEC and
      family planning services should target men and strong emphasis should be given to
      use of family planning methods in as early period after birth as possible.

PMID- 16999196
TI  - Histopathological types of breast cancer in Nigerian women: a 12-year review
      (1993-2004).
AB  - To determine the commonest histological types of breast cancer in Nigerian women
      in Edo State and the mean age at diagnosis, we reviewed the histological slides
      of breast cancer received in the pathology department of University of Benin
      Teaching Hospital over a twelve-year period (January 1993-December 2004). The
      clinical data was obtained from the original request form and case notes where
      necessary. The mean age of the patients was 45.7 (SD= 13.4, SEM = 0.7). Invasive
      ductal carcinoma (not otherwise specified) constituted the majority of breast
      cancer accounting for 75.5% while papillary carcinoma was the least common
      (2.7%). Ductal carcinoma in situ accounted for 6.6%. Breast cancer occur more on
      the left (53.3%) than the right (45.7%). Bilateral breast cancer was found in
      only 0.8% of the cases. The frequency of invasive breast cancer is still very
      high among Nigerian women. Late presentation possibly due to ignorance,
      alternative medicine and fear of surgery may account for this high prevalence.

PMID- 16999197
TI  - Rapid HIV testing and counselling in labour in a northern Nigerian setting.
AB  - Between April and August 2004, all pregnant women in labour at JUTH, were offered
      rapid HIV testing and counselling with opportunity to decline testing. HIV
      positive women were offered the standard nevirapine mono-therapy prophylaxis
      regimen (HIVNET 012). Four hundred and thirty (99.8%) of the 431 pregnant women
      who were offered rapid HIV testing and counselling, agreed to test. A sero
      conversion rate of 2.1% (5 of 235) was found among women who had previously
      tested negative for HIV during the index pregnancy. A seroprevalence rate of 9.6%
      (16 of 166) was found among women with unknown HIV status. One patient who had an
      indeterminate HIV status prior to labour tested positive in labour. Rapid HIV
      testing and counselling in labour is a useful practice in high prevalence
      settings since it detects a substantial number of HIV-infected women and HIV
      exposed babies that would otherwise have missed interventions to prevent MTCT.

PMID- 16999198
TI  - Teachers' attitude is not an impediment to adolescent sexuality education in
      Enugu, Nigeria.
AB  - Studies have shown that adolescents in Nigeria have poor knowledge of
      reproductive health issues and that there was a need to provide them with correct
      broad-based information on reproductive health as part of a nationally-approved
      school curriculum. However, the non-application of the curriculum on sexuality
      education in many secondary schools in Nigeria has been blamed on a negative
      attitude of teachers. This study was undertaken to determine the attitude of
      secondary school teachers in Enugu, South-eastern Nigeria, to adolescent
      sexuality education and to determine whether this depends on their socio
      demographic characteristics. A cross-sectional study of the attitude of teachers
      to adolescent sexuality education was done. A total of 249 teachers were studied.
      Their mean age was 38.7 years +/- 8.08 SD. Two hundred and ten teachers (84%)
      were females. Two hundred and twenty-four teachers (90%) were married and 168
      (67.5%) were of Roman Catholic faith. The awareness of reproductive health
      activities was high. There was a high proportion of respondents who approved of
      sexuality education for adolescents (77.5%) and an equally high proportion who
      believed that it was important (89%). One hundred and ninety-eight (79%) of the
      respondents were willing to teach sexuality education. The attitude to sexuality
      education was independent of religion, sex or marital status (p>0.05). It was
      concluded that secondary school teachers in Enugu urban were willing to offer
      sexuality education to adolescents under their care irrespective of their
      religion, sex or marital status. It is, therefore, recommended that teachers in
      Enugu be given the necessary special training in the teaching of sexuality
      education now and that sexuality education be officially incorporated into the
      school curriculum in Enugu, preferably as part of moral studies.

PMID- 16999199
TI  - An assessment of rural women's knowledge, constraints and perceptions on cervical
      cancer screening: the case of two districts in Zimbabwe.
AB  - This paper gives a sociological and anthropological insight into the rural
      women's perceptions and understanding of cervical symptomatology, screening and
      cancer. Qualitative data was collected through in-depth interviews and focus
      group discussions with women and health personnel. Quantitative data was obtained
      through questionnaires administered to 356 women from Mutoko and Shurugwi
      districts. The study revealed that cervical cancer is a disease that is of
      concern among health practitioners and women. 95.78% of the interviewed women had
      never gone for screening and had little knowledge about the various aspects of
      the disease in terms of causes, prevention and treatment. The study made four
      recommendations: the need for national screening policy and programme to be put
      in place, health education to women about cervical cancer, use of VIA in low
      resource settings and sensitisation of women about the availability of screening
      facilities in the districts where programmes are in place.

PMID- 16999200
TI  - Outcome of cardiopulmonary resuscitation in the intensive care units of a
      university hospital.
AB  - The purpose of this study is to evaluate the demographic characteristics of
      patients who suffered cardiac arrest in our ICUs and to identify those factors
      influencing outcome after resuscitation following cardiac arrest. We reviewed the
      records of all patients who underwent CPR in the two ICUs at the Georg-August
      University Hospital Goettingen, Germany from 1 January, 1999 to 31 December,
      2003. During the study period 169 patients underwent CPR and 80 of the 169
      patients survived to hospital discharge, giving a survival to hospital discharge
      rate of 47.3%. The initial monitored rhythm recorded at the time of arrest was
      asystole in 99 (58.6%) patients, ventricular tachycardia/fibrillation in 59
      (34.9%) and pulseless electrical activity in 7 (4.1%) patients. The respective
      survival rates were 46 (54.8%), 31 (36.9%) and 5 (6.0%) to hospital discharge. Of
      the 80 patients that survived to hospital discharge 75 (93.8%) achieved good
      cerebral recovery (CPC 1 or 2) and were alert and fully oriented on discharge; 4
      patients (5.0%) were severely disabled (CPC 3), while 1 (1.2%) remained
      unconscious and was reported dead five days after discharged to another local
      hospital. Illness severity as assessed by SAPS II score on admission was 38.8 +/-
      16.0. None of our patients with > 40 SAPS II score 24 hours after CPR survived to
      be discharged from the ICU. Our study showed that nearly half the patients that
      had cardiac arrest in our hospital ICUs had a favourable outcome despite initial
      rhythms that are traditionally associated with a poor outcome. This confirms that
      good results are achievable in these groups of patients.

PMID- 16999201
TI  - Corneal multiphoton microscopy and intratissue optical nanosurgery by nanojoule
      femtosecond near-infrared pulsed lasers.
AB  - Multiphoton microscopy including multiphoton autofluorescence imaging (MAI) and
      second-harmonic generation (SHG) is being used as a novel diagnostic tool to
      perform tissue nonlinear optical tomography with submicron resolution. The three
      dimensional corneal ultrastructure of whole depth has been viewed without any
      staining or mechanical slicing. Compared with photodisruptive surgical effects
      occurring at TW/cm2 light intensity, multiphoton imaging can be induced at MW-GW/
      cm2 photon intensity. The intratissue surgical effect including nanojoule (nJ)
      femtosecond laser ablation and flap generation was induced through multiphoton
      nonlinear absorption at a wavelength of 800 nm and ascertained by the
      histological outcomes. More interesting, the multiphoton microscopy based on
      nonlinear absorption of femtosecond laser pulses at the wavelength of 715-930 nm
      emitted from solid-state Ti:sapphire system is acting as a precise non-invasive
      monitoring tool to determine the interest of region, to visualize and verify the
      outcomes in in vivo intrastromal laser nanosurgery. Overall, these data suggest
      that multiphoton microscopy is a highly sensitive and promising technique for
      studying the morphometric and biomechanical properties of biological tissues and
      that the nJ ultrashort Lasers can be used as a ultra-precise nanoscalpel for
      performing intratissue surgery.

PMID- 16999202
TI  - Ciliary neurotrophic factor (CNTF) in the olfactory system of rats and mice.
AB  - The rodent olfactory system is a regarded model for the relationship between
      neurotrophic factors, their receptors, and their compound influence on the
      notable lifelong neuroplasticity occurring in this sensory system. It was known
      that high amounts of ciliary neurotrophic factor (CNTF), a hematopoietic
      cytokine, can be found in the olfactory bulb. In the awarded work, a detailed
      cellular characterization of CNTF-localization in the olfactory system was
      obtained. The results demonstrated CNTF-immunoreactivity in olfactory ensheathing
      cells, newborn interneurons in the olfactory bulb, and in a subpopulation of
      mature olfactory sensory neurons in the olfactory epithelium. Three-dimensional
      reconstructions of CNTF-immunoreactive axonal bulbar projections of these neurons
      revealed an ordered bilaterally symmetric pattern. This finding implies a
      potential connection between neuronal CNTF-expression in the olfactory epithelium
      and olfactory information processing.

PMID- 16999203
TI  - Detection of retroviruses in a calvaria of a young mouse.
AB  - During systematic examination of the development and growth of mouse calvariae,
      virus particles were detected electron microscopically. Mice, strain NMRI, were
      obtained from the breeder Harlan-Winkelmann (Borchem, Germany) and mated in the
      animal house. The area of the sagittal suture from day-18 foetuses and from
      different stages until day-26 pp as well as from adult mice was studied. In the
      calvaria of a day-21 pp mouse, type-C virus particles were found in the
      pericellular space of many, but not all osteogenic cells. The morphology of all
      viruses found resembled that of retroviruses; they were regular in size,
      spherical and showed a diameter of 100-120 nm. Budding of viruses from the
      osteocyte membrane occurred frequently. Also type-A particles were detected
      intracisternally within the rough endoplasmic reticulum. Budding of type-C virus
      particles, extracellular deposition of retroviruses and intracisternal formation
      of type-A particles occurred in the same cell. However, although examinations of
      22 different individual calvariae were done, only one obtained from a day-21 pp
      mice was virus-positive. Most probably, this observation is due to an endogenous
      virus production. Several mouse strains bear provirus DNA in their genome; the
      mode of activation of which is unknown. Reports in the literature are rare.
      Nevertheless, virus-infected material may influence experimental approaches and
      may be dangerous for the people who work with such material.

PMID- 16999204
TI  - A scanning electron microscopic study of nasal respiratory epithelium in pregnant
      rats.
AB  - Pregnancy is a very important period in mammals. Various morphological and
      functional changes can be observed. Some studies examining nasal epithelial
      structure deal with changes found in pregnancy. In this study, a total of 16
      adult female Sprague Dawley rats (8 control and 8 pregnant) were used. They were
      anesthetized with ketamine and sacrificed via cardiac perfusion with 2.5%
      glutaraldehyde solution (in 0.1 M sodium phosphate buffer, pH 7.4). The heads of
      the rats were bisected midsagittally and one half was completely passed through
      the routine histological procedures for SEM examination. On the apical surfaces
      of ciliated cells of pregnant rat respiratory epithelium disoriented cilia and
      cilia with dilated blebs at their free ends were observed. In addition, some
      masses of mucus due to hypersecretion were striking. Goblet cells appeared
      swollen and their apical surfaces showed microvilli varying considerably in
      length and number.

PMID- 16999205
TI  - Microvascular abnormalities in patients with rheumatoid arthritis.
AB  - Microvascular involvement represents one of the first apparent steps in many
      autoimmune diseases such as rheumatoid arthritis (RA). Early in the disease,
      peripheral microangiopathy may be easily recognized and studied by
      videocapillaroscopy. The aim of this study has been to observe the differences in
      labial microcirculation between healthy patients and patients suffering from RA.
      A total of 30 healthy patients and 30 patients suffering from RA were examined.
      The patients with conditions known to compromise microcirculation, such as
      diabetes, hypertension, or some pharmacological treatments were not included in
      the study. All the patients were non-smokers. Labial capillaroscopy was used to
      investigate the characteristics of microcirculation. Visibility, course,
      tortuosity, as well as the possible presence of microhemorrhages, the average
      caliber of the capillary loops and the number of visible capillary loops per
      square millimeter were evaluated for each patient. The investigation was simple,
      non-invasive, and repeatable for each patient. In patients suffering from RA, it
      was possible to observe a reduced caliber of capillaries, as well as greater
      elongated capillaries, in comparison to controls. This study shows that capillary
      alterations in patients suffering from RA occur in labial mucosa
      microcirculation; such evidence could be extremely important in the diagnosis of
      suspected RA.

PMID- 16999206
TI  - Three-dimensional characteristics of submandibular salivary gland of ageing rats:
      an HRSEM study.
AB  - The characteristics of the submandibular glands of ageing Wistar rats were
      studied using light and high-resolution scanning electron microscopy (HRSEM)
      methods. For light microscopy, the samples were fixed in Bouin solution and
      embedded in paraffin. Sections were stained with hematoxilin-eosin and Azo
      Carmin. For conventional scanning electron microscopy, the tissues were fixed in
      modified Karnovsky solution, and treated with NaOH solution for 3-4 days. The O-D
      O method was used for HRSEM. The samples were fixed in 2% osmium tetroxide,
      macerated in diluted osmium and dehydrated in an increasing series of ethanol.
      The samples were dried in a critical point dryer, coated with gold-palladium and
      examined in a Hitachi high-resolution scanning electron microscope, S-900. The
      results showed that submandibular glands with lobules are separated by connective
      tissue septum. The acinar formations and the ducts, revealing the serous and
      mucous cells were observed. After fracture in liquid nitrogen and treatment with
      NaOH solution to remove the cellular components, the original disposition of the
      collagen bundles fibers were revealed corresponding to the round, oval or
      irregular acinar and ductal structures. In the cytoplasm, organelles such as
      mitochondria, rough endoplasmic reticulum, Golgi apparatus and serous and mucous
      secretory granules were observed localized in the apical portion in three
      dimensional HRSEM images. The serous secretory granules presented different sizes
      and shapes showing the modifications which occurred in the ageing rats. The
      striated duct cells revealed the presence of the secretory cells and mitochondria
      in parallel disposition. The mitochondrial cristae were noted in three
      dimensional aspects. The lumen presented numerous cytoplasmic microprojections.
      The lumen of excretor ducts are covered by polygonal epithelial cells containing
      numerous microplicae.

PMID- 16999207
TI  - Ultramicroscopic study on the hair of newly found 15th century mummy in Daejeon,
      Korea.
AB  - Recent reports on the medieval mummies in Korea have been an invaluable source
      for the studies on the physical characteristics of medieval Koreans. Though the
      histological observations on the medieval mummy found in Korea were actively
      reported by researchers, it could not be said that all the queries on the mummies
      had been completely answered at the present time. In this study, we tried to add
      the novel data on the ultramicroscopic characteristics of the hair taken from the
      recently discovered 15th century mummy, the oldest one ever found in Korea. Even
      comparing with the hair from living individual, the hair of 15th century mummy
      showed very intact appearances during observation with electron microscope
      because the scales on the surface of the mummified hair were not damaged, which
      were not easily maintained even in living individuals. As to the cause of the
      excellent preservation of 15th century mummified hair, the presence of surface
      coat on the hair should be considered. That is, just like the complete sealing
      effect of lime-soil mixture barrier around the coffin, the presence of the
      surface coat including calcium and sodium might inhibit the water or fungal
      infiltrations into the hair shaft.

PMID- 16999208
TI  - Bilateral accessory thoracodorsal artery.
AB  - The subscapular artery arises from the third part of the axillary artery and
      gives off the circumflex scapular and the thoracodorsal arteries. Although
      anatomical variations of the axillary artery are very common, the existence of a
      unilateral accessory thoracodorsal artery has been described in the literature
      only once. There are no reports of bilateral accessory thoracodorsal artery, in
      the literature. In the present study, a bilateral accessory thoracodorsal artery,
      originating on either side of the third part of the axillary artery, is described
      in a 68-year-old female cadaver. All the other branches of the axillary artery
      had a typical origin, course, distribution and termination. This extremely rare
      anatomical variation apart from the anatomical importance also has clinical
      significance for surgeons in this area. Especially, during the dissection or
      mobilization of the latissimus dorsi that is partly used for coverage problems in
      many regions of the body and also in dynamic cardiomyoplasty, any iatrogenic
      injury of this accessory artery may result in ischemia and functional loss of the
      graft.

PMID- 16999209
TI  - Case report: description of a venous annulus of the external iliac vein.
AB  - This report describes a case of a venous annulus of the left external iliac vein.
      Above the inguinal ligament the external iliac vein divides into two branches,
      which are interlinked by a communicating branch, forming two loops. The first
      loop is situated around the external iliac artery, the second loop is found
      between the communicating branch and the common iliac vein. Although variations
      of the external iliac vein have already been reported, we could not find any
      description which would match to our observation.

PMID- 16999210
TI  - Complex renal vascular variation: a case report.
AB  - As the number of renal surgical interventions increase a better understanding of
      the anatomy of renal arteries and their branches gain in importance. Here we
      describe a common trunk from the right side of the aorta ramifying into
      suprarenal and two renal hilar arteries in a 40-year-old male cadaver detected
      during dissections performed in a routine gross anatomy course. The suprarenal
      branch is divided into several smaller branches to supply blood to the suprarenal
      gland. The superior renal hilar artery gave rise to the right testicular artery
      and an additional suprarenal artery. The inferior renal hilar artery gave rise to
      one more additional suprarenal artery. The superior renal hilar artery crossed
      the inferior renal hilar artery. On the same side renal veins were also doubled.
      For better outcome interesting variations such as in this case should be kept in
      mind before and during any interventions involving this region.

PMID- 16999211
TI  - Age-related changes in the anatomical landmarks of the osseous epipharynx.
AB  - We investigated age-related spatial relations of the osseous epipharynx--the
      region between the vomer and the anterior border of the great occipital foramen
      (basion) on 60 skulls of both sexes: 16 adult (age range 21-59 years), 19 aged
      (age range 60-86 years), and macerated occipital bones, sphenoid bones, and
      vomers in 25 specimens of children disarticulated skulls aged 1-15 years. We
      measured the distances basion-tuberculum pharyngeum, tuberculum pharyngeum-ala
      vomeris, tuberculum pharyngeum-crista choanalis vomeris, basion-crista choanalis
      vomeris, width of the pars basilaris at the level of the tuberculum pharyngeum,
      narrowest width of the pars basilaris, width at the level of pyramidal apexes;
      and width at the level of laminae mediates processus pterygoidei of the sphenoid
      bone. We found a statistically significant increase in the frontal and sagittal
      measurements of the osseous epipharynx increasing from childhood to adulthood,
      without further significant changes into old age. In the aged adult and skulls,
      the distance from the tuberculum pharyngeum to the basion was half the distance
      to the vomer, whereas in children the ratio of these distances was 1:3. The major
      difference in the bony landmarks of the osseous epipharynx between children and
      adults were the attachments of muscles, m. longus capitis and m. rectus capitis
      anterior. Whereas the most common morphological feature of the m. longus capitis
      attachment was a bony fossa lateral to the tuberculum pharyngeum, the muscle
      attached to a prominent crest in children. These previously unreported findings
      illustrate the role of muscle activity in the formation of osseous landmarks of
      the epipharynx.

PMID- 16999212
TI  - An unusual variation of the omohyoid muscle and review of literature.
AB  - The omohyoid muscle is important in radical neck dissection, as it is a landmark
      for this operation. Because it divides the anterior and posterior cervical
      triangles into smaller triangles and its particular relationship to the large
      cervical vessels, the presence of an anatomical variation of the omohyoid muscle
      is important. An unfamiliar muscle was found in the left anterior cervical region
      of a 57-year-old male cadaver. It was attached at its caudal end to the clavicle
      and coursed upward to the hyoid bone and a normal omohyoid muscle with its
      intermediate tendon was lateral to this muscle. Both the muscles joined together
      near the hyoid bone and both muscles attached to the hyoid bone with the same
      tendon. According to its origin and insertion, the unfamiliar muscle was
      considered to be the cleido-hyoideus muscle. In our case report, a variant of
      infrahyoid muscles is presented. Such an association constitutes an exceedingly
      rare condition.

PMID- 16999213
TI  - Anomalous muscle belly to the index finger.
AB  - An unusual variation of flexor digitorum superficialis was observed during the
      cadaver dissection. The flexor digitorum superficialis (FDS) had a normal origin
      and insertion, except to the index finger, where a muscle belly replaced the
      tendon of FDS. The unusual muscle belly originated as a continuation of FDS
      tendon in the carpal tunnel and inserted normally into the middle phalanx. A
      branch of the median nerve innervated the anomalous muscle belly. The anomalous
      muscle belly described here should be considered in the aetiology of carpal
      tunnel syndrome.

PMID- 16999214
TI  - A quantitative study on the sacrum of the dog.
AB  - The aim of this study was to record sacral bone morphometry that may help in
      selection of the implant type and proper size in sacroiliac separation. For this
      reason, sacral lengths and width, the length of each sacral vertebrae, distances
      between cranial and caudal articular processes, vertical and transversal
      diameters of the cranial endplate, sacral tuberositas and articular surface areas
      were obtained from 11 dogs. Additionally, the transverse and vertical diameters
      of the bony structure and sacral canal were measured from six cross-sections. The
      data of the study were determined to be representative of the sacral values for
      average-sized dogs, which was confirmed statistically. The highest value was the
      sacral width among the linear measurements. The ventral sacral length was longer
      than the dorsal sacral length. The total lateral area of the sacral wing was
      measured as 677.46 (142.1)mm2. The transverse diameters of the first sacral
      vertebra important for screw implantation were 46.02 (4.33)mm and 44.18 (5.29)mm
      in the first and second cross-sections, respectively.

PMID- 16999215
TI  - Normal endothelium.
AB  - In recent decades, it has become evident that the endothelium is by no means a
      passive inner lining of blood vessels. This 'organ' with a large surface
      (approximately 350 m2) and a comparatively small total mass (approximately 110 g)
      is actively involved in vital functions of the cardiovascular system, including
      regulation of perfusion, fluid and solute exchange, haemostasis and coagulation,
      inflammatory responses, vasculogenesis and angiogenesis. The present chapter
      focusses on two central aspects of endothelial structure and function: (1) the
      heterogeneity in endothelial properties between species, organs, vessel classes
      and even within individual vessels and (2) the composition and role of the
      molecular layer on the luminal surface of endothelial cells. The endothelial
      lining of blood vessels in different organs differs with respect to morphology
      and permeability and is classified as 'continuous', 'fenestrated' or
      'discontinuous'. Furthermore, the mediator release, antigen presentation or
      stress responses of endothelial cells vary between species, different organs and
      vessel classes. Finally there are relevant differences even between adjacent
      endothelial cells, with some cells exhibiting specific functional properties,
      e.g. as pacemaker cells for intercellular calcium signals. Organ-specific
      structural and functional properties of the endothelium are marked in the
      vascular beds of the lung and the brain. Pulmonary endothelium exhibits a high
      constitutive expression of adhesion molecules which may contribute to the
      margination of the large intravascular pool of leucocytes in the lung.
      Furthermore, the pulmonary microcirculation is less permeable to protein and
      water flux as compared to large pulmonary vessels. Endothelial cells of the blood
      brain barrier exhibit a specialised phenotype with no fenestrations, extensive
      tight junctions and sparse pinocytotic vesicular transport. This barrier allows a
      strict control of exchange of solutes and circulating cells between the plasma
      and the interstitial space. It was observed that average haematocrit levels in
      muscle capillaries are much lower as compared to systemic haematocrit, and that
      flow resistance of microvascular beds is higher than expected from in vitro
      studies of blood rheology. This evidence stimulated the concept of a substantial
      layer on the luminal endothelial surface (endothelial surface layer, ESL) with a
      thickness in the range of 0.5-1 microm. In comparison, the typical thickness of
      the glycocalyx directly anchored in the endothelial plasma membrane, as seen in
      electron micrographs, amounts to only about 50-100 microm. Therefore it is
      assumed that additional components, e.g. adsorbed plasma proteins or hyaluronan,
      are essential in constituting the ESL. Functional consequences of the ESL
      presence are not yet sufficiently understood and acknowledged. However, it is
      evident that the thick endothelial surface layer significantly impacts
      haemodynamic conditions, mechanical stresses acting on red cells in microvessels,
      oxygen transport, vascular control, coagulation, inflammation and
      atherosclerosis.

PMID- 16999216
TI  - Functional ultrastructure of the vascular endothelium: changes in various
      pathologies.
AB  - Biology has revealed that form follows function or function creates the organ.
      Translating this law at the cellular level, we may say that the ultrastructure
      follows function or function creates the ultrastructure. The vascular endothelium
      is an accurate illustration of this rule due to its numerous and many-sided
      functions carried out by highly specialised cells, structurally equipped for
      their tasks. Occupying a strategic position between the blood and tissues, the
      endothelial cell (EC) tightly monitors the transport of plasma molecules,
      employing bidirectional receptor-mediated and receptor-independent transcytosis
      and endocytosis, regulates the vascular tone, synthesises and secretes a large
      variety of factors, and is implicated in the regulation of cell cholesterol,
      lipid homeostasis, signal transduction, immunity, inflammation and haemostasis.
      Ultrastructurally, besides the common set of organelles, the characteristic
      features of the ECs are the particularly high number of vesicles (caveolae)
      endowed with numerous receptors, transendothelial channels, the specialised
      plasma membrane microdomains of distinct chemistry, and characteristic
      intercellular junctions. In addition, by virtue of their number (-6 x 10(13)),
      aggregated mass (-1 kg), large surface area (-7,000 m2) and distribution
      throughout the body, the ECs can perform all the assumed functions. The vascular
      endothelium, with its broad spectrum of paracrine, endocrine and autocrine
      functions, can be regarded as a multifunctional organ and chief governor of body
      homeostasis. The ECs exists in a high-risk position. The cells react
      progressively to aggressive factors, at first by modulation of the constitutive
      functions (permeability, synthesis), followed by EC dysfunction (loss, impairment
      or new functions); if the insults persist (in time or intensity), cell damage and
      death ultimately occur. In conclusion, the ECs are daring cells that have the
      functional-structural attributes to adapt to the ever-changing surrounding
      milieu, to use innate mechanisms to confront and defend against insults and to
      monitor and maintain the body's homeostasis.

PMID- 16999217
TI  - Development of the endothelium.
AB  - Our understanding of the regulation of vascular development has exploded over the
      past decade. Prior to this time, our knowledge of vascular development was
      primarily based on classic descriptive studies. The identification of stem cells,
      lineage markers, specific growth factors and their receptors, and signalling
      pathways has facilitated a rapid expansion in information regarding details of
      the mechanisms that govern development of the vascular system.

PMID- 16999218
TI  - Transport across the endothelium: regulation of endothelial permeability.
AB  - An important function of the endothelium is to regulate the transport of liquid
      and solutes across the semi-permeable vascular endothelial barrier. Two cellular
      pathways controlling endothelial barrier function have been identified. The
      transcellular pathway transports plasma proteins of the size of albumin or
      greater via the process of transcytosis in vesicle carriers originating from cell
      surface caveolae. Specific signalling cues are able to induce the internalisation
      of caveolae and their movement to the basal side of the endothelium. Caveolin-1,
      the primary structural protein required for the formation of caveolae, is also
      important in regulating vesicle trafficking through the cell by controlling the
      activity and localisation of signalling molecules that mediate vesicle fission,
      endocytosis, fusion and finally exocytosis. An important function of the
      transcytotic pathways is to regulate the delivery of albumin and immunoglobulins,
      thereby controlling tissue oncotic pressure and host-defence. The paracellular
      pathway induced during inflammation is formed by gaps between endothelial cells
      at the level of adherens and tight junctional complexes. Paracellular
      permeability is increased by second messenger signalling pathways involving Ca2+
      influx via activation of store-operated channels, protein kinase Calpha
      (PKCalpha), and Rho kinase that together participate in the stimulation of myosin
      light chain phosphorylation, actin-myosin contraction, and disruption of the
      junctions. In this review of the field, we discuss the current understanding of
      the signalling pathways regulating paracellular and transcellular endothelial
      permeability.

PMID- 16999219
TI  - Calcium signalling in the endothelium.
AB  - Elevations in cytosolic Ca2+ concentration are the usual initial response of
      endothelial cells to hormonal and chemical transmitters and to changes in
      physical parameters, and many endothelial functions are dependent upon changes in
      Ca2+ signals produced. Endothelial cell Ca2+ signalling shares similar features
      with other electrically non-excitable cell types, but has features unique to
      endothelial cells. This chapter discusses the major components of endothelial
      cell Ca2+ signalling.

PMID- 16999220
TI  - Eicosanoids and the vascular endothelium.
AB  - Cyclooxygenase (COX) enzymes catalyse the biotransformation of arachidonic acid
      to prostaglandins which subserve important functions in cardiovascular
      homeostasis. Prostacyclin (PGI2) and prostaglandin (PG)E2, dominant products of
      COX activityin macro- and microvascular endothelial cells, respectively, in
      vitro, modulate the interaction of blood cells with the vasculature and
      contribute to the regulation of blood pressure. COXs are the target for
      inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs--which include those
      selective for COX-2) and for aspirin. Modulation of the interaction between COX
      products of the vasculature and platelets underlies both the cardioprotection
      afforded by aspirin and the cardiovascular hazard which characterises specific
      inhibitors of COX-2.

PMID- 16999221
TI  - Nitric oxide and the vascular endothelium.
AB  - The vascular endothelium synthesises the vasodilator and anti-aggregatory
      mediator nitric oxide (NO) from L-arginine. This action is catalysed by the
      action of NO synthases, of which two forms are present in the endothelium.
      Endothelial (e)NOS is highly regulated, constitutively active and generates NO in
      response to shear stress and other physiological stimuli. Inducible (i)NOS is
      expressed in response to immunological stimuli, is transcriptionally regulated
      and, once activated, generates large amounts of NO that contribute to
      pathological conditions. The physiological actions of NO include the regulation
      of vascular tone and blood pressure, prevention of platelet aggregation and
      inhibition of vascular smooth muscle proliferation. Many of these actions are a
      result of the activation by NO of the soluble guanylate cyclase and consequent
      generation of cyclic guanosine monophosphate (cGMP). An additional target of NO
      is the cytochrome c oxidase, the terminal enzyme in the electron transport chain,
      which is inhibited by NO in a manner that is reversible and competitive with
      oxygen. The consequent reduction of cytochrome c oxidase leads to the release of
      superoxide anion. This may be an NO-regulated cell signalling system which, under
      certain circumstances, may lead to the formation of the powerful oxidant species,
      peroxynitrite, that is associated with a variety of vascular diseases.

PMID- 16999222
TI  - Angiotensin, bradykinin and the endothelium.
AB  - Angiotensins and kinins are endogenous peptides with diverse biological actions;
      as such, they represent current and future targets of therapeutic intervention.
      The field of angiotensin biology has changed significantly over the last 50
      years. Our original understanding of the crucial role of angiotensin II in the
      regulation of vascular tone and electrolyte homeostasis has been expanded to
      include the discovery of new angiotensins, their important role in cardiovascular
      inflammation and the development of clinically useful synthesis inhibitors and
      receptor antagonists. While less applied progress has been achieved in the kinin
      field, there are continuous discoveries in bradykinin physiology and in the
      complexity of kinin interactions with other proteins. The present review focuses
      on mechanisms and interactions of angiotensins and kinins that deal specifically
      with vascular endothelium.

PMID- 16999223
TI  - Endothelin.
AB  - In humans, the endothelins (ETs) comprise a family of three 21-amino-acid
      peptides, ET-1, ET-2 and ET-3. ET-1 is synthesised from a biologically inactive
      precursor, Big ET-1, by an unusual hydrolysis of the Trp21 -Val22 bond by the
      endothelin converting enzyme (ECE-1). In humans, there are four isoforms (ECE-1a
      d) derived from a single gene by the action of alternative promoters.
      Structurally, they differ only in the amino acid sequence of the extreme N
      terminus. A second enzyme, ECE-2, also exists as four isoforms and differs from
      ECE-1 in requiring an acidic pH for optimal activity. Human chymase can also
      cleave Big ET-1 to ET-1, which is cleaved, in turn, to the mature peptide as an
      alternative pathway. ET-1 is the principal isoform in the human cardiovascular
      system and remains one of the most potent constrictors of human vessels
      discovered. ET-1 is unusual in being released from a dual secretory pathway. The
      peptide is continuously released from vascular endothelial cells by the
      constitutive pathway, producing intense constriction of the underlying smooth
      muscle and contributing to the maintenance of endogenous vascular tone. ET-1 is
      also released from endothelial cell-specific storage granules (Weibel-Palade
      bodies) in response to external stimuli. ETs mediate their action by activating
      two G protein-coupled receptor sub-types, ETA and ET(B). Two therapeutic
      strategies have emerged to oppose the actions of ET-1, namely inhibition of the
      synthetic enzyme by combined ECE/neutral endopeptidase inhibitors such as SLV306,
      and receptor antagonists such as bosentan. The ET system is up-regulated in
      atherosclerosis, and ET antagonists may be of benefit in reducing blood pressure
      in essential hypertension. Bosentan, the first ET antagonist approved for
      clinical use, represents a significant new therapeutic strategy in the treatment
      of pulmonary arterial hypertension (PAH).

PMID- 16999224
TI  - Vascular endothelium and blood flow.
AB  - Major advances have been made over the last decade towards the elucidation of the
      molecular mechanisms involved in the endothelium-dependent regulation of vascular
      tone and blood flow. While the primary endothelium-derived vasodilator autacoid
      is nitric oxide, it is clear that epoxyeicosatrienoic acids and other endothelium
      derived hyperpolarising factors, as well as endothelin-1 and reactive oxygen
      species, play a significant role in the regulation of vascular tone and gene
      expression. This review is intended as an overview of the signalling mechanisms
      that link haemodynamic stimuli (such as shear stress and cyclic stretch) and
      endothelial cell perturbation to the activation of enzymes generating vasoactive
      autacoids.

PMID- 16999225
TI  - Biomechanical modulation of endothelial phenotype: implications for health and
      disease.
AB  - The functional phenotypic plasticity of the vascular endothelium relies on the
      ability of individual endothelial cells to integrate and transduce both humoral
      and biomechanical stimuli from their surrounding environments. Increasing
      evidence strongly suggests that biomechanical stimulation is a critical
      determinant of endothelial gene expression and the functional phenotypes
      displayed by these cells in several pathophysiological conditions. Herein we
      discuss the types of biomechanical forces that endothelial cells are constantly
      exposed to within the vasculature, explain how these biomechanical stimuli serve
      as regulators of endothelial function and discuss the increasing evidence that
      "atherosclerosis-protective" or "atherosclerosis-prone" haemodynamic environments
      can be important causative factors for atherogenesis via the differential
      regulation of endothelial transcriptional programmes.

PMID- 16999226
TI  - Leucocyte-endothelial interactions in health and disease.
AB  - The emigration of leucocytes into the tissue as a crucial step in the response to
      inflammatory signals has been acknowledged for more than 100 years. The
      endothelium does not only represent a mechanical barrier between blood and
      tissue, the circulatory system also connects different organ systems with each
      other, thus allowing the communication between remote systems. Leukocytes can
      function as messengers and messages at the same time. Failure or dysregulation of
      leucocyte-endothelial communication can severely affect the integrity of the
      organism. The interaction between leucocytes and the vascular endothelium has
      been recognised as an attractive target for the therapy of numerous disorders and
      diseases, including excessive inflammatory responses and autoimmune diseases,
      both associated with enormous consequences for patients and the health care
      system. There is promising evidence that the success rate of such treatments will
      increase as the understanding of the molecular mechanisms keeps improving. This
      chapter reviews the current knowledge about leucocyte-endothelial interaction. It
      will also display examples of both physiological and dysregulated leucocyte
      endothelial interactions and identify potential therapeutical approaches.

PMID- 16999227
TI  - Endothelial cell dysfunction, injury and death.
AB  - Vascular endothelial cells (ECs) perform a number of functions required to
      maintain homeostasis. Inflammation can cause EC injury and death which disrupt
      these processes and result in endothelial dysfunction. Three common mediators of
      EC injury in inflammation are macrophage-derived cytokines, such as tumour
      necrosis factor (TNF); neutrophil-generated reactive oxygen species (ROS) and
      cytolytic T lymphocytes (CTL). Here we describe the distinct but overlapping
      biochemical pathways of injury elicited by these different agents.

PMID- 16999228
TI  - Principles and therapeutic implications of angiogenesis, vasculogenesis and
      arteriogenesis.
AB  - The vasculature is the first organ to arise during development. Blood vessels run
      through virtually every organ in the body (except the avascular cornea and the
      cartilage), assuring metabolic homeostasis by supplying oxygen and nutrients and
      removing waste products. Not surprisingly therefore, vessels are critical for
      organ growth in the embryo and for repair of wounded tissue in the adult.
      Notably, however, an imbalance in angiogenesis (the growth of blood vessels)
      contributes to the pathogenesis of numerous malignant, inflammatory, ischaemic,
      infectious and immune disorders. During the last two decades, an explosive
      interest in angiogenesis research has generated the necessary insights to develop
      the first clinically approved anti-angiogenic agents for cancer and blindness.
      This novel treatment is likely to change the face of medicine in the next decade,
      as over 500 million people worldwide are estimated to benefit from pro- or anti
      angiogenesis treatment. In this following chapter, we discuss general key
      angiogenic mechanisms in health and disease, and highlight recent developments
      and perspectives of anti-angiogenic therapeutic strategies.

PMID- 16999229
TI  - The vascular endothelium in hypertension.
AB  - The vascular endothelium plays a fundamental role in the basal and dynamic
      regulation of the circulation. Thus, it has a crucial role in the pathogenesis of
      hypertension. A spectrum of vasoactive substances is synthesised in the
      endothelium; of these, nitric oxide (NO), prostacyclin (PGI2) and endothelin (ET)
      1 are the most important. There is a continuous basal release of NO determining
      the tone of peripheral blood vessels. Systemic inhibition of NO synthesis or
      scavenging of NO through oxidative stress causes an increase in arterial blood
      pressure. Also, the renin-angiotensin-aldosterone system has a major role in
      hypertension as it has a direct vasoconstrictor effect and important interactions
      with oxygen free radicals and NO. Prostacyclin, in contrast to NO, does not
      contribute to the maintenance of basal vascular tone of conduit arteries, but its
      effect on platelets is most important. ET acts as the natural counterpart to
      endothelium-derived NO and has an arterial blood pressure-raising effect in man.
      Anti-hypertensive therapy lowers blood pressure and may influence these different
      mediators, thus influencing endothelial function. In summary, due to its position
      between the blood pressure and smooth muscle cells responsible for peripheral
      resistance, the endothelium is thought to be both victim and offender in arterial
      hypertension. The delicate balance of endothelium-derived factors is disturbed in
      hypertension. Specific anti-hypertensive and anti-oxidant treatment is able to
      restore this balance.

PMID- 16999230
TI  - Vascular endothelium and atherosclerosis.
AB  - Atherosclerosis depends critically on altered behavior of the intrinsic cells of
      the artery wall, the endothelial cells and smooth muscle cells, and inflammatory
      leukocytes that join them in the arterial intima during the atherogenic process.
      The homeostatic properties of the normal endothelium contribute importantly to
      maintenance of aspects of arterial health including the appropriate regulation of
      blood flow, a basal anti-inflammatory state, promotion of fibrinolysis while
      opposing blood coagulation, and control of the balance of cellular proliferation
      and death. Alterations in these endothelial homeostatic mechanisms contribute
      critically to atherogenesis, the progression of this disease, and ist
      complications. Recent advances have highlighted novel molecular mechanisms that
      regulate the atheroprotective functions of normal endothelial cells that go awry
      during atherogenesis. Therapeutic strategies that alter the course of
      atherosclerosis may act by combating endothelial dysfunction.

PMID- 16999231
TI  - Endothelial cells and cancer.
AB  - Endothelial cells play a key role in the development and function of blood and
      lymph vessels. Excessive proliferation and transformation of endothelial cells
      lead to pathological angiogenesis/lymphangiogenesis or vascular malfunctions
      which are hallmarks of malignant disorders. There is emerging evidence that
      circulating endothelial progenitor cells (EPCs) also contribute significantly to
      these processes. Major progress has been achieved over the past few years in the
      identification of key molecules involved, and in targeting tumour angiogenesis
      for human therapy. Current research efforts are concentrated on deciphering the
      origin and functional properties of endothelium in various tumours, as well as
      endothelial neoplasms themselves. The aim of these studies is to investigate the
      molecular mechanisms regulating mobilisation of EPCs from bone marrow, and their
      homing and differentiation into mature endothelium in situ at sites of
      neovascularisation, as well as the role of viral oncogenes in regulating the
      plasticity and extending the life span of endothelial cells. Integrated
      understanding of the mechanisms regulating the properties and function of
      endothelial cells during tumourigenesis is resulting in the development of a
      number of exciting and bold approaches for the treatment of cancer.

PMID- 16999232
TI  - Gene therapy: role in myocardial protection.
AB  - Heart failure associated with coronary artery disease is a major cause of
      morbidity and mortality. Recent developments in the understanding of the
      molecular mechanisms of heart failure have led to the identification of novel
      therapeutic targets which, combined with the availability of efficient gene
      delivery vectors, offer the opportunity for the design of gene therapies for
      protection of the myocardium. Viral-based therapies have been developed to treat
      polygenic and complex diseases such as myocardial ischaemia, hypertension,
      atherosclerosis and restenosis. Some of these experimental therapies are now
      undergoing clinical evaluation in patients with cardiovascular diseases. In this
      review we will focus on the latest advances in the field of gene therapy for
      treatment of heart failure and their clinical application.

PMID- 16999233
TI  - [Leptospirosis].
AB  - Leptospirosis is the most common zoonosis worldwide, although most cases occur in
      tropical countries. Leptospira interrogans, a spirochete, is the causative agent.
      Rats are the main reservoir. Most patients present a mild clinical form of the
      disease, which consists of a self-limited febrile process, without jaundice.
      Nevertheless, about 10% of patients suffer severe infections, with intense
      jaundice. Typically the disease manifests in two phases: acute or leptospiremic
      and immune or leptospiuric, although in many patients the two phases are
      indistinguishable, and in mild cases the second one is frequently absent.
      Diagnosis is carried out by serology or culture of the microorganism. Treatment
      consists of antibiotics such as penicillin G, ceftriaxone, doxycycline or
      amoxicillin.

PMID- 16999234
TI  - [Markers of thyroid function (I). Assessment of glandular activity].
AB  - Thyroid hormones have a fundamental role in the metabolism, and are active in all
      organs and systems. Thyroid dysfunction (TD) is an important public health
      problem that concerns 10% of the general population. Diagnosis of TD is currently
      carried out on the basis of serum hormone levels determined by laboratory
      analysis. The results are classified into clinical (TSH and thyroid hormones out
      of normal range) and subclinical (isolated TSH disorder) dysfunction. The
      development of third generation assays in the TSH test represents a great step
      forward in the diagnosis of TD. However, the debate about the pathological
      significance of subclinical TD has intensified. There is as yet no agreement on
      the best approach for diagnosis and treatment of this common condition. It is
      currently impossible to know which subjects with subclinical TD will develop the
      typical complications of clinical dysfunction. In this setting, it is feasible
      that a number of subclinical hypothyroid subjects may in some cases be
      overtreated with thyroxin, while others remain undertreated with increased
      iatrogenic morbidity as a consequence.

PMID- 16999236
TI  - [Diagnostic performance of mammography in patients with clinically impercetible
      tumors. Analysis of 1005 tumors].
AB  - Breast cancer is an important public health problem. Early diagnosis is the only
      method of efficient secondary prevention in the control of the illness as it
      permits rapid and effective treatment. The objective of this study was to carry
      out a methodical analysis that would enable us to increase the diagnostic
      performance of the mammogram and to diminish the number of unnecessary surgical
      biopsies. MM: We selected impalpable mammary tumors in patients with radiological
      suspicion of breast cancer, on which surgical biopsy by harpoon had been
      practiced in the Lozano Blesa Hospital, Zaragoza, between October 1991 and
      January 2005. RESULTS: We analyzed a total of 1005 tumors in 965 patients, with
      an average age of 57 years. In our series of 1005 tumors, 40% were PVV.
      CONCLUSIONS: The diagnosis of radiological suspicion and the indication for
      biopsy or mammographic control are subjective and personal appreciations, but
      based on the systematic analysis of radiological signs of incipient tumors. This
      analysis enables us to establish a cut-off point to include the tumors in BIRADS.

PMID- 16999235
TI  - [Markers of thyroid function (II). Assessment of tissue action].
AB  - Advances in molecular medicine have increased our knowledge of the consequences
      of hormone action in target cells. We are currently able to determine to some
      extent the molecular thyroid hormone activity in different organs. The effects
      are related with a variety of factors, but their association with plasmatic
      hormone levels is only partially correlated. Recent advances indicate that there
      are several intermediate factors in thyroid tissue activity. The iodothyronine
      selenodeiodinases have a relevant role in this context. The clinical and
      biochemical methods currently available for thyroid function assessment do not
      permit us to explore many of these new elements. However, it is well known that
      thyroid hormones enhance the expression of a number of proteins, and some of
      these can be measured by simple methods. Accordingly, the plasmatic value of
      these proteins may be related with the effect of thyroid hormones in the target
      tissues, which is the result of thyroid function. The ability to determine the
      tissue activity of thyroid hormones will enable us to administrate the treatment
      dose more accurately, only to patients who require it, avoiding iatrogenism.

PMID- 16999237
TI  - [Case report article: ovulation and Diane-35, current perspectives in detection
      and control of fertility].
AB  - This is a case report article describing a patient receiving treatment for
      alopecia with Diane-35, in whom a recruited dominant follicle and a cumulus
      oophorus were detected by ultrasound. The current perspectives in the detection
      and control of fertility are discussed and subjected to critical analysis, with
      emphasis on some results concerning artificial birth control. The recognition of
      the ovulatory period through physiological changes, the detection of estrogeno-3
      glucuronide (E3G) and the luteinizing hormone (LH) is discussed. These methods
      increase the possibility of understanding the detection of the fertile phase in
      women, are simple to use, are not invasive, do not have secondary effects, and
      are not abortive.

PMID- 16999238
TI  - [Competence, heart, service. Medicine and christian love].

PMID- 16999239
TI  - Whole-cell sensing for a harmful bloom-forming microscopic alga by measuring
      antibody--antigen forces.
AB  - Aureococcus anophagefferens, a harmful bloom-forming alga responsible for brown
      tides in estuaries of the Middle Atlantic U.S., has been investigated by atomic
      force microscopy for the first time, using probes functionalized with a
      monoclonal antibody specific for the alga. The rupture force between a single
      monoclonal antibody and the surface of A. anophagefferens was experimentally
      found to be 246 +/- 11 pN at the load rate of 12 nN/s. Force histograms for A.
      anophagefferens and other similarly-sized algae are presented and analyzed. The
      results illustrate the effects of load rates, and demonstrate that force-distance
      measurements can be used to build biosensors with high signal-to-noise ratios for
      A. anophagefferens. The methods described in this paper can be used, in
      principle, to construct sensors with single-cell resolution for arbitrary cells
      for which monoclonal antibodies are available.

PMID- 16999240
TI  - Effect of pore size on the calculated pressure at biological cells pore wall.
AB  - A transient nonlinear finite-element program has been used to calculate the
      electric field distribution as a function of time for a spherical cell with a
      pore in a conducting medium during application of a subnanosecond rise time
      "step" wave, including the effects of dipolar saturation in the water-based
      cytoplasm and cell medium. The time-dependent pressure on the pore wall has been
      computed as a function of time as the system polarizes from the change of the
      energy in the electric field to the left (inside the pore) and to the right
      (inside the membrane) of the pore wall. The computations suggest that dipolar
      saturation, while significant, has little effect on the time-dependent electric
      field distribution but a substantial effect on the field-induced pore wall
      pressure. Also, the effect of pore size on both the computed electric field and
      field-induced pressure was studied. As the pore size increases, a collapse in
      both the electric field and field-induced pressure has been noticed. This
      suggests that as the pore size increases, the driving force for further opening
      the pore is not electrical.

PMID- 16999241
TI  - Application of the Taguchi method to the analysis of the deposition step in
      microarray production.
AB  - Every microarray experiment is affected by many possible sources of variability
      that may even corrupt biological evidence on analyzed sequences. We applied a
      "Taguchi method" strategy, based on the use of orthogonal arrays to optimize the
      deposition step of oligonucleotide sequences on glass slides. We chose three
      critical deposition parameters (humidity, surface, and buffer) at two levels
      each, in order to establish optimum settings. A L8 orthogonal array was used in
      order to monitor both the main effects and interactions on the deposition of a 25
      mer oligonucleotide hybridized to its fluorescent-labeled complementary. Signal
      background ratio and deposition homogeneity in terms of mean intensity and spot
      diameter were considered as significant outputs. An analysis of variance (ANOVA)
      was applied to raw data and to mean results for each slide and experimental run.
      Finally we calculated an overall evaluation coefficient to group together
      important outputs in one number. Environmental humidity and surface-buffer
      interaction were recognized as the most critical factors, for which a 50%
      humidity, associated to a chitosan-covered slide and a sodium phosphate + 25%
      dimethyl sulfoxide (DMSO) buffer gave best performances. Our results also
      suggested that Taguchi methods can be efficiently applied in optimization of
      microarray procedures.

PMID- 16999242
TI  - Principles and design of a novel magnetic force mechanical conditioning
      bioreactor for tissue engineering, stem cell conditioning, and dynamic in vitro
      screening.
AB  - Mechanical conditioning of cells and tissue constructs in bioreactors is an
      important factor in determining the properties of tissue being produced.
      Mechanical conditioning within a bioreactor environment, however, has proven
      difficult. This paper presents the theoretical basis, design, and initial results
      of a mechanical conditioning system for cell and tissue culture which is based on
      biocompatible magnetic micro- and nanoparticles acting as a remote stress
      mechanism without invasion of the sterile bioreactor environment.

PMID- 16999243
TI  - All-optical switching in Pharaonis phoborhodopsin protein molecules.
AB  - Low-power all-optical switching with pharaonis phoborhodopsin (ppR) protein is
      demonstrated based on nonlinear excited-state absorption at different
      wavelengths. A modulating pulsed 532-nm laser beam is shown to switch the
      transmission of a continuous-wave signal light beam at: 1) 390 nm; 2) 500 nm; 3)
      560 nm; and 4) 600 nm, respectively. Simulations based on the rate equation
      approach considering all seven states in the ppR photocycle are in good agreement
      with experimental results. It is shown that the switching characteristics at 560
      and 600 nm, respectively, can exhibit negative to positive switching. The
      switching characteristics at 500 nm can be inverted by increasing the signal beam
      intensity. The profile of switched signal beam is also sensitive to the
      modulating pulse frequency and signal beam intensity and wavelength. The
      switching characteristics are also shown to be sensitive to the lifetimes of
      ppR(M) and ppR(O) intermediates. The results show the applicability of ppR as a
      low-power wavelength tunable all-optical switch.

PMID- 16999244
TI  - Forming microstructured alkanethiol self-assembled monolayers on gold by laser
      ablation.
AB  - A process to form microstructured alkanethiol self-assembled monolayers (SAMs) on
      gold is described. It is well known that alkanethiols spontaneously form
      homogenous SAMs on gold surfaces. By means of laser ablation, the exposed areas
      of alkanethiol monolayers can be removed from the gold surface. Free gold is
      obtained which can react further with second and third thiols. By this technique,
      structured alkanethiol SAMs are obtained reliably and easily. In a rather narrow
      window of pulse intensities, in our example 120 MW/cm2 +/- 10% from a frequency
      doubled Nd: YVO4 laser with 6-ns pulsewidth operating at a repetition rate of 20
      kHz, ablation of alkanethiol monolayers is obtained without causing any damage to
      the gold substrate. Examples are presented where lines down to 10 microm in width
      were laser ablated into an SAM formed either from a hydrophilic or a hydrophobic
      alkanethiol and filled with a monolayer of a second alkanethiol of opposite
      hydrophilicity. The patterned structures were examined by optical and
      fluorescence microscopy as well as by lateral force microscopy. The presented
      method enables the preparation of microstructured SAMs on gold and probably on a
      wide variety of other substrates.

PMID- 16999245
TI  - Transient block of receptor may be a mechanism controlling unidirectional
      propagation of signaling.
AB  - In tissue development, juxtacrine signaling often propagates across cells,
      carrying and delivering temporal and spatial information for cells to make
      correct patterning. Observed complex and accurate tissue patterning indicates
      that signaling propagation via ligand-receptor interactions is precisely
      controlled. It is important and interesting to reveal the possible control
      mechanisms. The directionality of signaling in cells, which is a common issue for
      all intercellular signaling pathways, is a critical aspect. To understand the
      propagation of Notch signaling in presomitic mesoderm cells in the mouse, a novel
      method is used to build a multicellular model to simulate Notch signaling.
      Simulation reveals that the transient block of Notch by Notch induced Lfng and
      the delayed removal of the block by another Notch induced protein Hes7 may
      explain the observed unidirectional propagation of Notch signaling in these
      cells. Both mutation in and overexpression of lfng cause the same signaling
      profile in the tissue, due to the inappropriate timing of Notch signaling block
      by Lfng. The reverse Notch/Delta signaling quickly develops into reciprocating
      signaling among cells, causing irregular expression of cyclic genes. Irregular
      Notch signaling in cells would change their response to the positional
      information provided by the Fgf8 gradient, resulting in disordered and irregular
      somite segmentation. As Notch signaling is highly conserved, we hypothesize that
      the mechanism of controlling unidirectional propagation of signaling in cells by
      transient receptor block may exist in other tissues and in other vertebrates. Our
      simulation results also suggest that segmentation clock and unidirectional
      propagation may be inherently coupled in Notch signaling.

PMID- 16999246
TI  - Using carbon nanotubes to absorb low-concentration hydrogen sulfide in fluid.
AB  - Hydrogen sulfide is a colorless and flammable gas under room temperature. Usually
      hydrogen sulfide is considered to be toxic; however, the recent research revealed
      that hydrogen sulfide in the cardiovascular system plays the role of a vascular
      dilator. The physiological role of hydrogen sulfide depends on its in vivo level.
      As such, the measurement of hydrogen sulfide with nano-quantity resolution
      becomes an important subject. Existing methods generally require bulky samples
      and are invasive and offline. It will be significantly helpful to measure
      hydrogen sulfide with a small amount of tissue in a noninvasive method The first
      attempt was to take a blood or serum sample with a trace amount to examine the
      interaction between hydrogen sulfide and carbon nanotube. The carbon nanotube is
      chosen because of a known fact that hydrogen sulfide can be adsorbed by activated
      carbon. The carbon nanotube is an excellent activated carbon in this regard.
      Fluorescence intensity of the carbon nanotube with and without immersion of it in
      a hydrogen sulfide medium was examined in the study. It was found that the
      intensities increase as the concentrations of hydrogen sulfide increase.
      Furthermore, the concentration of 10 microM hydrogen sulfide in water was
      successfully measured.

PMID- 16999247
TI  - Biological crystallization of self-aligned iron oxide nanoparticles.
AB  - Crystal growth and magnetic behavior of iron oxide nanoparticles assembled with
      biomolecules have been investigated. The nanoparticles assembled with trypsin
      molecules exhibit superparamagnetism at room temperature with blocking
      temperature (approximately 80 K) significantly lower than those without trypsin
      (approximately 140 K). This is attributed to reduced magnetostatic couplings
      between particles due to increased distance between particles separated by
      trypsin molecules. Moreover, the synthesized nanoparticle-biomolecule assemblies
      consist of a unique one-dimensional self-assembled arrays of nanoparticles found
      by structural analysis using transmission electron microscopy. The moire fringes
      observed from the particle arrays indicate that the particles are aligned with
      slight misorientation of their crystallographic axes. Such an unusual formation
      of nanoparticle arrays may be relevant to specific ligand sites in trypsin
      molecules and the magnetostatic interparticle couplings.

PMID- 16999248
TI  - Light-induced in situ patterning of DNA-tagged biomolecules and nanoparticles.
AB  - We present an in situ method for the selective manipulation of DNA-tagged nano
      objects such as vesicles or gold colloids in aqueous solution, at neutral pH. The
      method makes use of the photosensitizer concept found in photodynamic therapy.
      Here, single-stranded DNA is immobilized onto a surface via the
      biotin/streptavidin linkage. If the streptavidin is fluorescently labeled,
      reactive species will be created during laser-induced photobleaching of the
      label. These reactive species can then completely or partly suppress the DNA
      hybridization and cause the removal of the streptavidin. The technique thereby
      enables a dynamic on-off control over surface density of immobilized DNA-tagged
      nano-objects. Furthermore, combining this in situ manipulation of DNA with
      prepatterning of single-stranded DNA in the micro and later in the nano range
      provides a means for the dynamic patterning required for applications in
      biosensing and nanotechnology.

PMID- 16999249
TI  - Auditory training.

PMID- 16999250
TI  - The need for and development of an adaptive Listening and Communication
      Enhancement (LACE) Program.
AB  - Auditory training has long been advocated to enhance communication but has never
      been time or cost-effective. This article describes the concepts underlying the
      development of a home-based, interactive adaptive computer program designed to
      engage the adult hearing-impaired listener in the hearing-aid-fitting process,
      provide listening strategies, build confidence, and address cognitive changes
      characteristic of the aging process. An investigation using a between-group,
      within-subject design with pre- and post-test objective and subjective measures
      was conducted at five clinical sites. Sixty-five subjects were randomly placed
      into two groups, one receiving LACE (Listening and Communication Enhancement)
      immediately following baseline testing and one serving as a control for one month
      and then receiving training as a crossover group. Results showed statistically
      significant improvements for the trained subjects on all but one of the outcome
      measures. Barriers facing the widespread implementation of home-based aural
      rehabilitation are discussed.

PMID- 16999251
TI  - The use of cortical auditory evoked potentials to evaluate neural encoding of
      speech sounds in adults.
AB  - There has been considerable recent interest in the use of cortical auditory
      evoked potentials (CAEPs) as an electrophysiological measure of human speech
      encoding in individuals with normal as well as impaired auditory systems. The
      development of such electrophysiological measures such as CAEPs is important
      because they can be used to evaluate the benefits of hearing aids and cochlear
      implants in infants, young children, and adults that cannot cooperate for
      behavioral speech discrimination testing. The current study determined whether
      CAEPs produced by seven different speech sounds, which together cover a broad
      range of frequencies across the speech spectrum, could be differentiated from
      each other based on response latency and amplitude measures. CAEPs were recorded
      from ten adults with normal hearing in response to speech stimuli presented at a
      conversational level (65 dB SPL) via a loudspeaker. Cortical responses were
      reliably elicited by each of the speech sounds in all participants. CAEPs
      produced by speech sounds dominated by high-frequency energy were significantly
      different in amplitude from CAEPs produced by sounds dominated by lower-frequency
      energy. Significant effects of stimulus duration were also observed, with shorter
      duration stimuli producing larger amplitudes and earlier latencies than longer
      duration stimuli. This research demonstrates that CAEPs can be reliably evoked by
      sounds that encompass the entire speech frequency range. Further, CAEP latencies
      and amplitudes may provide an objective indication that spectrally different
      speech sounds are encoded differently at the cortical level.

PMID- 16999252
TI  - Evaluation of a probe-tube insertion technique for measuring the real-ear-to
      coupler difference (RECD) in young infants.
AB  - A common strategy for measuring the real-ear response of the real-ear-to-coupler
      difference (RECD) in the pediatric population is to insert a probe-tube
      separately from the eartip. This strategy is at times difficult to implement
      while attempting to obtain the measurement from a young infant. An RECD probe
      tube insertion technique that involves connecting the probe-tube to an eartip
      with plastic film for simultaneous insertion was examined on 30 infants. Repeated
      measurements were completed on each infant to obtain within-session test-retest
      reliability data. Probe-tube insertion depth was also examined across
      participants to provide a guideline for the infant population. Findings indicate
      that reliable RECD values can be obtained in infants when the probe-tube is
      extended approximately two to four millimeters (mm) beyond the eartip or 11 mm
      from the entrance to the ear canal. Clinical implications of this work are
      discussed.

PMID- 16999253
TI  - Amplitude-modulated auditory steady-state responses in younger and older
      listeners.
AB  - The primary purpose of this investigation was to determine whether temporal
      coding in the auditory system was the same for younger and older listeners.
      Temporal coding was assessed by amplitude-modulated auditory steady-state
      responses (AM ASSRs) as a physiologic measure of phase-locking capability. The
      secondary purpose of this study was to determine whether AM ASSRs were related to
      behavioral speech understanding ability. AM ASSRs showed that the ability of the
      auditory system to phase lock to a temporally altered signal is dependent on
      modulation rate, carrier frequency, and age of the listener. Specifically, the
      interaction of frequency and age showed that younger listeners had more phase
      locking than old listeners at 500 Hz. The number of phase-locked responses for
      the 500 Hz carrier frequency was significantly correlated to word-recognition
      performance. In conclusion, the effect of aging on temporal processing, as
      measured by phase locking with AM ASSRs, was found for low-frequency stimuli
      where phase locking in the auditory system should be optimal. The exploration,
      and use, of electrophysiologic responses to measure auditory timing analysis in
      humans has the potential to facilitate the understanding of speech perception
      difficulties in older listeners.

PMID- 16999254
TI  - Efficacy of a new treatment maneuver for posterior canal benign paroxysmal
      positional vertigo.
AB  - Existing treatment maneuvers for posterior canal benign paroxysmal positional
      vertigo (PC-BPPV) include the Semont liberatory maneuver (SLM) and canalith
      repositioning maneuver (CRM). Independent investigations reveal that these
      maneuvers provide an excellent outcome for most patients. However, certain
      aspects of these maneuvers, such as hyperextension of the neck for CRM and brisk
      lateral motion for the SLM, are contraindicated for patients with vertebrobasilar
      insufficiency, cervical spondylosis, back problems, and so forth. A hybrid
      approach, the Gans repositioning maneuver (GRM) was developed for use with these
      patients. The purpose of this project was to assess efficacy of the GRM for
      treatment of PC-BPPV. Two-hundred seven participants were enrolled in this
      prospective study. All participants were treated with the GRM. Six different
      clinicians performed the treatments. Participants returned for follow-up at one
      week intervals until it was determined that the PC-BPPV was clear. On average,
      1.25 GRM treatments were required to resolve the PC-BPPV. The majority of the
      participants (80.2%) were cleared with one GRM treatment, and 95.6% were clear
      after two treatments. Recurrence rate was 5%. There was no difference in outcome
      based on clinician. The GRM is an efficacious treatment maneuver for PC-BPPV and
      may be preferential for use in patients with neck, back, hip, and/or mobility
      issues that contraindicate the use of SLM or CRM.

PMID- 16999255
TI  - Frequency-modulation (FM) technology as a method for improving speech perception
      in noise for individuals with multiple sclerosis.
AB  - Almost half of the population with multiple sclerosis (MS) complains of
      difficulty hearing, despite having essentially normal pure-tone thresholds. The
      purpose of the present investigation was to evaluate the effects of frequency
      modulation (FM) technology utilization on speech perception in noise for adults
      with and without MS. Sentence material was presented at a constant level of 65
      dBA Leq from a loudspeaker located at 0 degrees azimuth. The microphone of the FM
      transmitter was placed 7.5 cm from this loudspeaker. Multitalker babble was
      presented from four loudspeakers positioned at 45 degrees, 135 degrees, 225
      degrees, and 315 degrees azimuths. The starting presentation level for the babble
      was 55 dBA Leq, The level of the noise was increased systematically in 1 dB steps
      until the subject obtained 0% key words correct on the IEEE (Institute for
      Electrical and Electronic Engineers) sentences. Test results revealed significant
      differences between the unaided and aided conditions at several signal-to-noise
      ratios.

PMID- 16999256
TI  - Homogeneity of the 18 QuickSIN lists.

PMID- 16999257
TI  - Endotracheal education begets patient safety: methods of minimizing risks and
      nosocomial infections. Interview by Robert Neil.

PMID- 16999258
TI  - A year in the making.

PMID- 16999259
TI  - Integrating the supply chain.

PMID- 16999260
TI  - Assessing capital equipment needs for your organization.

PMID- 16999261
TI  - Automated scope test spots costly leaks.

PMID- 16999262
TI  - Save time and money with supply chain automation.

PMID- 16999263
TI  - Michigan hospitals focus on infection control initiatives.

PMID- 16999264
TI  - How are you tracking your instruments and equipment?

PMID- 16999265
TI  - Epidemiology and therapeutic aspects of burn injuries in Slovakia (1993-2003).
AB  - The authors analyze the epidemiology and trend of thermal injuries in Slovakia
      since 1990. The article includes statistics from both of the burn injury
      workplaces in Bratislava and Kosice. The article contains conclusions and
      proposals for preventive measures which have contributed to the decrease of
      thermal injuries in Slovakia since 2000.

PMID- 16999266
TI  - The use of artificial skin in plastic surgery and burns.
AB  - The use of artificial skin restores the depth and the elasticity of the skin,
      through restoration of the dermis, with no significant morbidity. Thus we have
      permanent release of contractures and a pleasing contour with satisfactory
      functional and cosmetic results. Still, these advantages must be weighed against
      the necessity for meticulous surgical technique and intensive post-operative
      care, the waiting period and the cost of the product.

PMID- 16999267
TI  - Our experience in the nutritional support of a burned child treated with integra.
AB  - Integra artificial skin was applied on 16% of TBSA after necrectomy on a 7-month
      old girl who was scalded on 26% of TBSA by her mother when she was cooking
      goulash. Nutritional parameters were monitored during the period of 25 days from
      the 1st necrectomy and application of Integra up to the first autotransplantation
      -in the period when the other burnt surfaces were almost healed. The average
      intake of proteins and energy to achieve normal levels of monitored nutritional
      parameters was lower than that recommended by calculations for similarly burnt
      children. Our observation is similar to that of King.

PMID- 16999268
TI  - Current trends in safety assurance for tissue grafts used in burn treatment.
AB  - The author presents a summary of current safety standards for allogeneic and
      xenogeneic biological skin grafts. The fundamental document relevant to
      allogeneic transplants, establishing the minimal level of safety guaranteed in
      European Union states, is the European Parliament and Council Directive
      (2004/23/EC) from March 31st 2004. This Directive determines that grafts will be
      prepared by a licensed or accredited tissue bank, and that this arrangement must
      be put in place by the member states within 2 years. In the Czech Republic
      licensing of tissue banks took place immediately after issuance of the Directive.
      Licensing was also a condition for product reimbursement by insurance companies.
      To gain a licence, tissue banks had to fulfil many safety criteria associated
      with screening of living or deceased donors for health suitability, providing
      traceability of the donor-recipient route, prevention of secondary and cross
      contamination during processing and storage of the harvested tissues, proof of
      product microbiology check up, and cold chain control. The Tissue Bank of the
      Faculty Hospital in Hradec Kralove is one of the two tissue banks that gained the
      broader type of 'multifunctional' licence and was granted registration number MTB
      006. Obtaining the licence was facilitated by completion of a new workplace
      project conceived as a combination of cryogenic and clean-room technology.
      Currently, this tissue bank prepares cryopreserved dermoepidermal and dermal
      grafts as well as amnion and chorioamnion grafts. All tissue banks will have to
      renew their licences again according to the conditions established by a new law
      about human tissues and cells which is currently in preparation. Neither the
      Directive of the European Parliament nor the Transplantation Law of the Czech
      Republic regulates the issue of xenografts. Since availability of allogeneic
      biological covers is limited, it is significant that the WHO perspective on the
      use of xenogeneic biological covers, as established in 2005, is positive. This
      attitude should also be taken in the Czech Republic. The directives of the
      European Union pertinent to medical devices of biological origins can be applied
      only to devitalized tissues--and moreover, the domestic pig is not on the risk
      animal list. The author presumes that to guarantee safe use of viable xenografts
      it is necessary to follow the general principles of quality control as applied in
      the workplace for many years, as well as general medicinal product safety
      principles, including strict veterinary control of breed of animals whose tissues
      are used for the preparation of xenografts.

PMID- 16999269
TI  - Cutometrical measurement confirms the efficacy of the composite skin grafting
      using allogeneic acellular dermis in burns.
AB  - Measurement of viscoelasticity of the skin using the device called cutometer
      seems to be a very precise and promising diagnostic method in different skin
      pathologies. However, only a very limited number of reports dealing with the use
      of cutometer in burns is available. The composite skin grafting using an
      allogeneic acellular dermis covered with a thin epidermal autologous graft is
      supposed to improve viscoelastic properties of grafted skin in full-thickness
      burns. Cutometer MPA 580 has been used for examination of healthy skin, healed
      and maturated autologous split-thickness skin grafts, and in two patiens 6 years
      after composite skin grafting using the allogeneic acellular dermis + thin
      autologous epidermal graft in one stage. Typical curves defined by values of R0
      R9 parameters are presented. These data document significantly better
      viscoelastic properties of composite skin grafts than those of conventional split
      thickness skin grafts after 6 years. Measurements of viscoelasticity of the skin,
      using a cutometer, will probably bring useful and precise data for evaluation of
      the reconstructed skin in burns. Significantly better properties of the composite
      skin graft were assessed clinically and measured by Cutometer MPA 580 6 years
      after surgery.

PMID- 16999270
TI  - Skin grafting options at the Burn and Reconstructive Surgery Department of the
      Faculty Hospital in Bratislava.
AB  - Replacement of devastated or severely damaged skin presents a key problem in the
      treatment of extensive deep burns in humans. The skin is an organ serving many
      functions, which can be replaced with skin transplants or temporary skin
      replacements only up to a certain extent. At the Burn and Reconstructive Surgery
      Department of the Faculty Hospital in Bratislava, located in Ruzinov, we have
      been concerned with the problem of skin replacement since its establishment in
      1987. In this article we review skin replacement options and our experience with
      indications and use of various types of skin substitutes, mainly of biological
      origin, such as allotransplants, xenotransplants and amnion.

PMID- 16999271
TI  - Military surgery at the turn of the century.
AB  - The authors present a summary of current postgraduate education status in the
      field of military clinical specializations with the focus on surgery and military
      surgery. Recent organizational changes in medical care within the Czech Army,
      along with changes associated with the new legal directives regulating the
      acquirement of professional and specialized medical qualification, will require a
      new approach to the training of surgeons and other physicians in the Czech
      Republic. This will involve new educational goals, adaptation of specialized
      curricula and introduction of systematic quality measurement methods of teaching
      and training.

PMID- 16999272
TI  - [Abdominal intercostal neuralgia: a forgotten cause of abdominal pain].
AB  - Four patients, 3 women aged 39, 36 and 58 and a man aged 51, had been
      experiencing recurring bouts of abdominal pain for periods varying from a few
      months to years. The pain could be provoked by palpation of a small circumscript
      area in the lower abdomen. A positive Carnett's sign (pain intensification during
      palpation while contracting the abdominal muscles by raising the head, whilst
      lying flat) may aid the diagnosis. An injection ofa local anaesthetic agent
      confirmed the diagnosis of nerve entrapment and appeared therapeutic in one
      patient. The other three patients experienced long-term relief following surgical
      nerve excision. Establishing a diagnosis in patients with abdominal cutaneous
      nerve entrapment syndrome is often delayed due to physicians being unaware of
      this condition. Most patients have to undergo numerous investigations including
      laparoscopies and explorative laparotomies, often to no avail. This syndrome
      should be considered in patients with chronic abdominal pain syndromes.

PMID- 16999273
TI  - [Plea for the retention of the Dutch National Medical Registration (LMR) to
      provide reliable information regarding public health and healthcare].
AB  - Since 1963, information on each hospital admission has been collected from all
      general and university hospitals in the Netherlands (the 'Landelijke Medische
      Registratie'; LMR). This information includes, among others, one main discharge
      diagnosis and up to nine secondary diagnoses made during admission, the duration
      of the hospital stay, death during admission, times of admission and discharge,
      type of specialist who treated the patient, operations and related therapeutic
      procedures. This information system is not biased by financial incentives and is
      therefore a good resource for epidemiological studies and drug-safety research.
      As of 2005, a new type of administration has been introduced that records
      diagnosis-therapy combinations for reimbursement purposes. Because the
      reimbursement of closely related diagnosis-therapy combinations may differ, the
      system is not only sensitive to fraud but will probably also jeopardise the
      validity of epidemiological research with such data. Therefore, the LMR system
      cannot be missed.

PMID- 16999274
TI  - [Advances in the surgical treatment of hypoplastic left-heart syndrome].
AB  - Hypoplastic left-heart syndrome is a congenital heart malformation that is
      classified as a univentricular disorder (hearts with only one functioning
      ventricle). Treatment was first developed in 1977, but a marked improvement in
      survival was not seen until the last decade. This was due primarily to a better
      understanding of how to surgically and medically manipulate the balance between
      pulmonary and systemic circulation. Special attention should be given to cerebral
      protection before, during and after surgery and to the follow-up of
      neurocognitive behaviour.

PMID- 16999275
TI  - [Rheumatic diseases as risk factors for cardiovascular disease].
AB  - Cardiovascular disease is the leading cause of death in patients with rheumatoid
      arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus
      (SLE). In addition to mortality, cardiovascular morbidity is also markedly
      increased in these patients, compared with the general population. The increased
      cardiovascular risk can be explained only partially by an increased prevalence of
      classical risk factors for cardiovascular disease; it also appears to be related
      to inflammation. Prospective intervention trials aimed at the modification of
      cardiovascular risk factors are needed to determine the impact of cardiovascular
      risk reduction in patients with rheumatic disease. In addition to SLE, RA and AS
      should be acknowledged as new risk factors for cardiovascular disease.

PMID- 16999276
TI  - [Late-onset hypogonadism in men: uncertain disease entity and reservations
      regarding treatment with testosterone].
AB  - Late-onset hypogonadism (LOH) is defined as insufficient testosterone levels in
      combination with associated psychological, somatovegetative and sexual symptoms
      in elderly men. Because the symptomatology of LOH is not specific, it is unclear
      whether LOH can be considered a clinically relevant entity. At this time,
      treatment of LOH with testosterone has been shown to have favourable effects on
      body composition only. The risks of treatment with testosterone appear to be
      minimal when absolute contraindications (prostate cancer) are observed, although
      long-term studies on the safety of testosterone therapy are lacking. Restraint in
      the diagnosis and treatment of LOH is therefore warranted.

PMID- 16999277
TI  - [Diagnostic image (289). A woman with the sensation that an internal air bubble
      comes up].
AB  - A 35-year-old woman was analysed because she had the recurrent sensation of an
      internal air bubble coming up. She was suffering from a gastric leiomyoma in the
      cardia-fundus area, which was removed laparoscopically.

PMID- 16999278
TI  - [Favourable results with surgical treatment in 43 children with hypoplastic left
      heart syndrome or similar disorders, 1999-2005].
AB  - OBJECTIVE: To describe the results of surgical treatment of hypoplastic left
      heart syndrome (HLHS) and HLHS-like disorders in the Amsterdam-Leiden Centre for
      Congenital Heart Disease, the Netherlands. DESIGN: Retrospective, descriptive.
      METHOD: Data were collected on 43 neonates with HLHS or similar disorders who
      underwent surgical treatment between December 1999 and December 2005. HLHS was
      present in 37 patients and 6 had disorders similar to HLHS (unbalanced
      atrioventricular septal defect, truncus arteriosus with hypoplastic left
      ventricle, double inlet left ventricle). Surgery was performed in 3 steps:
      Norwood operation shortly after birth (n = 43), bidirectional cavopulmonary
      anastomosis a few months later (n = 30) and total cavopulmonary connection at the
      age of 2-3 years (n = 10). During the Norwood operation, the first 21 patients
      received a modified Blalock shunt (between the right brachiocephalic artery and
      pulmonary artery), whereas the following 22 patients received a Sano shunt
      (between the right ventricle and pulmonary artery). RESULTS: Of the 43 patients,
      11 died: 7 within 30 days of the first operation, 2 between the first and second
      operation, and 2 between the second and third operation. Actuarial survival for
      the entire group is 74% (32/43). The mortality rate was lower with the Sano shunt
      (9%; 2/22) than with the modified Blalock shunt (43%; 9/21). Catheter
      interventions were necessary in 10 patients: 6 had balloon dilatation of the
      distal aortic arch and 4 had balloon dilatation/stent placement for narrowed
      pulmonary arteries. With a median follow-up of 22 months (range: 1-75), 2
      patients had marked neurological side effects. All 32 surviving patients were in
      good clinical condition.

PMID- 16999279
TI  - [A man with FIP1L1/PDGFRA-positive chronic eosinophilic leukemia].
AB  - A 39-year-old man was referred from Surinam to the Onze Lieve Vrouwe Gasthuis,
      Amsterdam, the Netherlands, for a right ventricular tumour, hypereosinophilia and
      mild thrombocytopenia. He appeared to have chronic eosinophilic leukaemia that
      was positive for the 'FIP1-like-1-platelet-derived growth factor receptor alpha'
      (FIP1L1-PDGFRA) gene. In addition, he had signs of a right ventricular thrombus
      that had existed for at least 6 months. The patient was treated with oral
      anticoagulants and the tyrosine kinase inhibitor imatinib. The latter therapy
      resulted in normalisation of leukocyte count and differential values. After 3
      months of therapy, the FIP1L1-PDGFRA fusion transcript was no longer detectable
      in peripheral blood. After 1 year of follow up, the patient was in complete
      haematological and molecular remission for chronic eosinophilic leukaemia. The
      cardiac mass remained unchanged, but caused no haemodynamic problems.

PMID- 16999280
TI  - [The syndrome of inappropriate antidiuretic hormone secretion (SIADH) during
      treatment with the antipsychotic agents haloperidol and quetiapine].
AB  - A 45-year-old man with paranoid schizophrenia repeatedly developed hyponatraemia
      due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), both
      after treatment with haloperidol and after taking quetiapine. This side effect
      did not occur subsequently during clozapine treatment. SIADH has been described
      in connection with almost all psychotropic drugs. Since the risk of developing
      SIADH is increased with increasing age, comorbid somatic disorders and
      polypharmacy, and the mean age of the psychiatric patient will further increase
      in the years to come, the physician should be alert to the risk factors and the
      clinical symptoms of disturbances in water balance; moreover, the proper
      differential diagnostic deliberations should be made. In case of increased risk,
      it is recommended to monitor the serum sodium during the first 2-4 weeks of
      pharmacotherapy.

PMID- 16999281
TI  - [Double-blind placebo-controlled cow's milk challenge for children in general
      hospitals].

PMID- 16999282
TI  - The new HPV vaccine--be sure you know the facts.

PMID- 16999283
TI  - You just can't trust the histories.

PMID- 16999284
TI  - Improving outcomes in renal disease.
AB  - CKD is a silent medical problem that requires laboratory analysis to make an
      early diagnosis. Early aggressive management of diabetes mellitus, hypertension,
      and dyslipidemia are vital. Awareness and management of the frequent
      complications also improve ESRD outcomes. Ongoing consultation with the
      nephrology team, including a renal dietitian, is important for delaying disease
      progression and improving patient quality of life.

PMID- 16999285
TI  - Practical approaches to screening for domestic violence.

PMID- 16999286
TI  - Depression--An independent risk factor for cardiovascular disease.

PMID- 16999287
TI  - DNA, race, and a new era in medicine.

PMID- 16999288
TI  - The management of clavicle fractures.

PMID- 16999289
TI  - Screening for osteoporosis.

PMID- 16999290
TI  - Patient information. Should I have a DEXA scan?

PMID- 16999291
TI  - Umbilical lesion appears in a woman with a history of sun exposure.

PMID- 16999292
TI  - Case of the Month. Lyme arthritis.

PMID- 16999293
TI  - Why do they wheeze?

PMID- 16999294
TI  - A 6-month-old boy with seizures.

PMID- 16999295
TI  - A brain tumor presenting as recurrent right upper lobe pneumonia.

PMID- 16999296
TI  - Aerosol delivery to children.

PMID- 16999297
TI  - The role of respiratory viruses in the pathogenesis of pediatric asthma.
AB  - The role of respiratory viral infection in the development of asthma remains
      unclear. A number of factors play crucial roles, including the type of virus, the
      severity of the disease, the time of the infection, and, most important, the host
      predisposition. On the other hand, there is little doubt that a strong
      association exists between viral respiratory infections and induction of wheezing
      illnesses and asthma exacerbations. The underlying mechanisms, although not fully
      clarified, are likely to be multifactorial, involving inflammation of the
      bronchial mucosa, which interacts under certain circumstances with allergic
      inflammation. In addition, repetitive infections play an important role in
      perpetuating inflammation and airway hyperresponsiveness, especially in the
      presence of atopy, leading from childhood asthma to a more persistent asthma
      phenotype.

PMID- 16999298
TI  - Environmental factors and childhood asthma.
AB  - Indoor allergens are potent triggers for acute and chronic pediatric asthma.
      Environmental control measures of these allergens should be considered first-line
      treatment measures. Allergen avoidance can produce changes in disease activity
      and symptoms that can be beneficial before any medical intervention is
      implemented. In addition to allergen avoidance, studies evaluating other
      exposures, such as endotoxin and diet, in the pathogenesis of asthma are in
      progress. Understanding the complex relationships between exposure and
      allergy/asthma development is vitally important to the development of potentially
      more effective primary and secondary prevention strategies.

PMID- 16999300
TI  - Asthma management: turning the mirror on ourselves.

PMID- 16999299
TI  - Managing asthma in the 21st century: role of pharmacogenetics.
AB  - As discussed above, pharmacogenetics offers the opportunity to ascertain
      associations between genetic variability and response (both salutary and adverse)
      to various asthma medications. Although there have been multiple asthma
      pharmacogenetic studies, the field of pharmacogenetics is still in its infancy.
      As this field advances, it is estimated that an increasing proportion of
      individual variation in responses to pharmacotherapy will be predictable based on
      associations with particular genetic polymorphisms or patterns of polymorphisms.
      These associations hold out the promise of being able to individualize
      pharmacotherapy by providing specific therapy to those most likely to respond,
      while avoiding therapy in those most likely to suffer adverse effects. Currently,
      only the pharmacogenetic effects of position 16 of the beta-adrenergic receptor
      appear to be of sufficient magnitude to affect asthma therapy, but further
      understanding of the mechanism of this association as well as prospective
      replication with long-acting beta-agonists is still required to bring
      pharmacogenetics into the clinical arena. Most other pharmacogenetic effects are
      likely to be of smaller magnitude or, as with 5-LO or CRHR1 polymorphisms, less
      common. Thus, ultimately, we most likely will use "panels" of polymorphisms to
      calculate the relative risk-benefit ratio of a particular therapeutic course for
      an individual patient. It is hoped that, within the next decade, pharmacogenetic
      information will allow us to treat those who can benefit most from particular
      asthma medications and to avoid toxicity by administering medications to those
      unlikely to experience toxicity. If pharmacogenetics fulfills its promise, then
      not only will we be able to administer corticosteroids and other therapies to
      pediatric patients with asthma who are most likely to respond or to those least
      likely to experience adverse effects but we also will be able to introduce or
      develop drugs for asthma that would otherwise have been held back due to
      potential toxicity in a subset of patients.

PMID- 16999301
TI  - Not lifting. Some patients really can walk.

PMID- 16999302
TI  - Doing things right. Are you committed to delivering high-quality care on every
      call?

PMID- 16999303
TI  - All abuzz. Angry bees ignite an unexpected MCI.

PMID- 16999304
TI  - Media relations for EMS managers.

PMID- 16999305
TI  - Leadership tips. Pennies: assess people's value before you let them go.

PMID- 16999306
TI  - Being a player. How NAEMT is positioning itself for the 21st century.

PMID- 16999308
TI  - Word on the street: part 2.

PMID- 16999307
TI  - Masters of the ordinary. For EMS, the fifth anniversary of 9/11 is less about
      major disasters than surviving day by day.

PMID- 16999309
TI  - The myth of the perfect model.

PMID- 16999310
TI  - Vehicle safety 2006. Part 3: Attitude adjustment.

PMID- 16999311
TI  - Views from the field. Interview by Raphael M Barishansky and Matthew R Streger.

PMID- 16999312
TI  - Primal quest Utah 2006.

PMID- 16999313
TI  - Demystifying the central line.
AB  - In the prehospital setting, you are most likely to encounter a PICC line, Port-A
      Cath or Hickman catheter. Others exist, but your chances of seeing them in the
      field are rare. The basic steps outlined in this article are an introduction to
      using central lines. I strongly recommend a handson session with a knowledgeable
      instructor who is intimately familiar with the use of these devices.

PMID- 16999314
TI  - Beyond the basics: geriatric care.

PMID- 16999315
TI  - Geriatric trauma.

PMID- 16999316
TI  - Taking EMS into tomorrow: part 5.

PMID- 16999317
TI  - Splenic arteriovenous fistula with infarcted spleen.
AB  - A 25-year-old woman developed epigastralgia and abdominal bruit in the left
      hypochondrium. Radiologic investigation included Doppler ultrasonography,
      angiography and computed tomography and revealed splenic artery aneurysm and
      arteriovenous fistula resulting in an almost totally infarcted spleen.

PMID- 16999318
TI  - MR imaging of the pelvic floor.
AB  - Pelvic floor disorders are a common clinical problem. Clinical evaluation
      frequently underestimates the extent of the disease. Fluoroscopic
      colpocystodefecography (CCD) is an established tool for diagnosing disorders of
      the rectum and recto- anal junction. It is however less performant when it comes
      to evaluate the complex pelvic floor mechanism in all its aspects. MR
      defecography allows to evaluate all the compartments of the pelvis without being
      invasive. This article describes the clinical setting, the MR technique and
      provides guidelines for interpretation of a MR defecography study.

PMID- 16999319
TI  - CT and MR imaging of gastrointestinal tuberculosis.
AB  - The purpose of this study was to describe the CT and MR imaging findings of
      tuberculosis of the gastrointestinal tract. Abdominal and pelvic CT scans and MRI
      studies of 6 patients with histopathological and microbiological proven
      intestinal tuberculosis were reviewed by two radiologists in consensus. Location
      and pattern of bowel wall involvement, signal intensities in relation to the
      normal bowel wall, pattern of enhancement and associated abdominal abnormalities
      were evaluated. Gastrointestinal tract tuberculosis may be limited to one bowel
      segment, with the cecum and ileocecal valve as the predominant site of disease,
      or may involve multiple bowel segments. Asymmetric thickening of the bowel wall
      is a common finding. Associated findings include pericecal and mesenteric fat
      stranding, regional lymphadenopathy showing peripheral, heterogeneous and/or
      homogeneous enhancement patterns and less commonly, tuberculous 'dry plastic'
      peritonitis. On magnetic resonance (MR) imaging, tuberculous bowel involvement
      results in intermediate decreased signal intensities on T1-weighted images, and
      intermediate increased, slight heterogeneous signal intensities on T2-weighted
      images. On contrast-enhanced images, slight heterogeneous enhancement is seen.

PMID- 16999321
TI  - Omental infarction in childhood.
AB  - We present a case of right-sided omental infarction in a child documented with
      ultrasound and multislice computed tomography and confirmed by surgery and
      pathologic examination. Omental infarction is a rare cause of right-sided acute
      abdominal pain in a child. Differential diagnosis includes appendicitis. With
      different imaging modalities a diagnosis can be made and avoid unnecessary
      appendectomy.

PMID- 16999320
TI  - Jaw fixation as the key to diagnosis of fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva is a very rare and disabling hereditary
      disorder of connective tissue characterised by symmetric congenital anomalies of
      the great toes and thumbs and by progressive heterotopic ossification of tendons,
      ligaments, fasciae and striated muscles. In this case we report a 17-year-old boy
      who presented with a painful swelling of the right mandibula with trismus.
      Multiple heterotopic soft tissue calcifications, severe scoliosis and typical
      anomalies of toes and thumbs on the radiographs were pathognomonic for
      fibrodysplasia ossificans progressiva.

PMID- 16999322
TI  - Giant splenic artery aneurysm presenting as unusual cause of obstructive
      jaundice.
AB  - Giant splenic aneurysms larger than 8 cm (GSAA) are rare and often asymptomatic
      but present an increased risk of dramatic rupture, a life-threatening
      complication. The management of these aneurysms is especially challenging. We
      probably report the first case of GSAA revealed by clinical mechanical jaundice
      due to direct compression of the biliary tree. The lesion was diagnosed during
      abdominal ultrasound in a 68-year-old patient but determination of the specific
      splenic origin and extensive anatomic preoperative evaluation were achieved by
      MDCT. The case illustrates the new high quality performances of MDCT in the
      evaluation of complex vascular abdominal situations and is presented with a brief
      review of the relevant literature.

PMID- 16999323
TI  - Imaging of soft tissue tumors: general imaging strategy and technical
      considerations.
AB  - This paper reviews the imaging strategy and protocol for detection, grading and
      staging, and posttherapeutic follow-up of soft tissue tumors (STT), used in our
      institution. The role of each imaging technique, with emphasis on magnetic
      resonance imaging, is highlighted.

PMID- 16999324
TI  - Imaging of lipomatous soft tissue tumors.
AB  - The purpose is to give an overview of the imaging features of benign and
      malignant lipomatous tumors. Imaging characteristics which are helpful in the
      differential diagnosis between benign and malignant subtypes are highlighted.

PMID- 16999325
TI  - Imaging of vascular soft tissue tumors.
AB  - Most tumors of the vascular system are benign, cutaneous or subcutaneous lesions
      that are usually readily diagnosed without significant differential diagnosis. On
      the other hand, lesions that arise in deep soft tissues have to be differentiated
      from malignant neoplasms. In these cases, further imaging work-up is necessary
      for local staging and planning therapy. Vascular lesions of intermediate
      malignancy and malignant vascular tumors are very rare and demonstrate
      nonspecific imaging findings. This manuscript aims to give a brief overview of
      vascular soft-tissue tumors and to discuss the imaging appearances.

PMID- 16999326
TI  - Imaging features of peripheral neurogenic tumors.
AB  - Peripheral nerve sheath tumors (PNST) include schwannoma, neurofibroma and
      malignant peripheral sheath tumors. All neurogenic tumors share the same imaging
      characteristics, including fusiform shape, low attenuation on CT, fascicular
      sign, split fat sign and associated muscle atrophy. The aim of this article is to
      give a comprehensive overview of peripheral nerve tumors and to discuss the
      imaging characteristics that distinguish these masses.

PMID- 16999327
TI  - Imaging of joint tumors.
AB  - The paper gives an overview of the present nosological classification and imaging
      features of synovial tumors and tumor-like conditions of joints. The merits of
      each imaging technique will be emphasized.

PMID- 16999328
TI  - Primary epiploic appendagitis: US and CT findings.

PMID- 16999329
TI  - Acute disseminating encephalomyelitis (ADEM).

PMID- 16999330
TI  - Clinicians on the front line: active management of depression and anxiety in
      primary care.
AB  - Primary-care practitioners confront myriad issue in managing their patients with
      depression and/or anxiety. Understanding the scope and epidemiology of these
      disorders is essential to understanding their shared characteristics. Do we
      always recognize these patients in practice? What are the barriers to diagnosis
      and treatment, and how can they overcome? What are the treatment options of these
      sometimes life-altering conditions, and how do we choose from among the many that
      exist?

PMID- 16999331
TI  - Individual health insurance market has lots of shoppers, few buyers.

PMID- 16999332
TI  - Long shifts for medical interns cause errors, injuries.

PMID- 16999333
TI  - PPAC to CMS: stop the 10-percent RVU cut.

PMID- 16999335
TI  - [Student evaluation of faculty teaching in molecular anatomy course at Nippon
      Medical School: results of a questionnaire survey].
AB  - For the purpose of improving education, the lecture and practices employed in the
      Molecular Anatomy Course were evaluated by students. The survey was performed
      with personal computer connected to a local area network and the results were
      readily exhibited on our website the following day. The total number of answers
      was 528 and the reply percentage was 31.2%. The average score (from 1: very bad
      to 5: very good) was 3.9, with a range of 3.2 to 4.8. Faculty teaching got better
      grades in the latter half of the period compared to those in the first half,
      particularly on "preparation" and "understanding". The correlation analysis
      showed a strong relationship between the understanding of the lecture and the
      orientation of practice. These findings suggest that constant evaluation by
      students during the whole period of the instruction is useful for improving the
      quality of education of our Anatomy Course.

PMID- 16999334
TI  - [Reexamination of the communicating branch between the sural and tibial nerves].
AB  - Reexamination of communicating branches between the sural and tibial nerves
      ventral to the calcanean tendon was carried out on 52 legs of 26 Japanese
      cadavers which were used for ordinary dissection practices at the Niigata
      University School of Medicine. Communicating branches were found in 7 out of 52
      dissections (13.5% of cases). In three of the 7 specimens, the communicating
      branch, the sural nerve and the tibial nerve with the deep crural fascia were
      removed from the legs and demonstrated by a modified Sihler's staining technique.
      Three types of communicating branches, Y, U and N, were distinguished on the
      basis of their shapes. In type Y, a medial branch from the sural nerve and a
      branch from the tibial nerve joined in Y-shape and become one terminal branch. In
      type U, the both branches formed a loop between the sural and tibial nerves. The
      type N communicating branch ran obliquely and medially to reach the tibial nerve
      distally. Only the Y type appeared in 5 specimens. Both the Y and U type and the
      Y and N types occurred in one specimen each. We assume that the communicating
      branch of the N type contains motor fibers which are derived from the sural nerve
      and innervate some plantar muscles, because this type is correspond to the
      communication type of some animals in which motor fibers have been demonstrated.
      Therefore, if the sural nerve biopsy is performed to examine a pure sensory
      nerve, removal of the more distal part of the sural nerve than a diverging point
      of a communicating branch is recommended. This study also indicated that the
      modified Sihler's staining technique is useful to examine distributions of
      cadaveric peripheral nerves after medical students' dissection course.

PMID- 16999336
TI  - [Is the incidence of schizophrenia declining?: an investigation of the
      examination rates in the psychiatric clinics of a medical school hospital and a
      general hospital].
AB  - PURPOSE: Some researchers in Europe, America and Oceania have recently reported
      that the incidence of schizophrenia is declining. We investigated changes in the
      proportion of schizophrenic patients to the total number of patients in two
      Japanese hospitals during the last decade. SUBJECTS AND METHODS: The subjects
      were patients who first consulted the psychiatric clinic of Jichi Medical School
      or the psychiatric clinic of Kamitsuga General Hospital between December 1993 and
      November 1994 or between December 2003 and November 2004. Both clinics accepted
      new patients without prior appointments. Patients were classified using ICD-10
      criteria (F0-F9, G40). The sex distribution of the patients and the mean age at
      first contact were compared for the two time periods. The proportion of
      schizophrenia (F2 in the ICD-10 criteria) to the total number of patients was
      compared for the two time periods after standardizing the populations with regard
      to age using the "1985 model population in Japan." RESULTS: A decade ago, 398
      patients first contacted the psychiatric clinic of the medical school hospital,
      compared with 958 patients in the recent investigation. A decade ago, 166
      patients first contacted the psychiatric clinic of the general hospital, compared
      with 407 patients in the recent investigation. No differences in the sex ratios
      of the two groups were noted. The mean age of the patients visiting the medical
      school significantly increased by 3.5 years (36.9 to 40.4 years), while that of
      the patients visiting the general hospital significantly increased by 10.0 years
      (46.2 to 56.2 years). The proportion of schizophrenia patients in the medical
      hospital decreased from 8.5% to 6.9%, while that in the general hospital
      decreased from 11.0% to 5.4%. Only the change in the proportion of schizophrenia
      patients at the general hospital was significant. CONCLUSION AND DISCUSSION: The
      facts that the mean age of first-contact patients has risen and that the number
      of first-contact patients has increased approximately 2.5-fold suggests a change
      in the composition of first-contact patients in the last decade. We have some
      reservations regarding the comparison of these two groups. Although the actual
      number of first-contact patients with schizophrenia increased in both clinics, we
      found that the proportions of schizophrenia patients decreased in both clinics
      after standardizing the populations with regard to age. This finding must be
      investigated in view of other factors, including the overall age distribution of
      first-contact patients, increases in the proportions of affective disorders and
      organic mental disorders, and so on.

PMID- 16999337
TI  - [Case with probable dementia with Lewy bodies, who shows reduplicative paramnesia
      and Capgras syndrome].
AB  - We report a case of probable dementia with Lewy bodies (DLB), showing
      reduplicative paramnesia (RP) and Capgras syndrome (CS). The patient, a right
      handed 60 year-old male, began to show progressive dementia. At the age of 65, he
      showed fluctuating cognitive impairment and recurrent visual hallucinations. His
      SPECT demonstrated hypoperfusion not in the medial temporal cortices, but in the
      parieto-occipital lobes, where the right hemisphere was dominantly hypoperfused.
      He was diagnosed with probable DLB. In addition to recurrent visual
      hallucinations, he showed a sense of self- (or others) transfiguration,
      consciousness of something non-existent (Leibhaftige Bewusstheit; Jaspers, K.),
      and fluctuating visuo-spacial impairment. At the age of 67, he gradually
      complained of his duplicative wives "sosie". Finally he went so far as to talk
      about a nameless phantom boarder. We considered that RP and CS of this case
      comprised a sense of self-(or others) transfiguration, misidentification of
      important persons and places, and productive symptoms such as consciousness of
      something non-existent (Leibhaftige Bewusstheit) and visual hallucinations. The
      above mentioned symptoms might be originated not only from the disturbance of
      visuospacial recognition, which involves the limbic system (especially amygdala),
      medial frontal cortex, and right hemisphere of the brain, but also from the
      disturbance of recursive consciousness, due to diffusely damaged brain regions
      with Lewy body pathology. (Authors' abstract)

PMID- 16999338
TI  - [Role of outpatient psychiatry in therapy of patients with eating disorder].
AB  - Eating disorders are common illness but the proportion of those in treatment is
      still low and their liability to abandon treatment is a constant danger. This is
      largely due to the pathology: in particular splitting and denial. Thus, the
      integration of various types of treatment is essential and the process of
      integration will be efficiently managed if a psychiatric clinic works as a center
      of the therapeutic network. Formerly, long-term in-patient treatment was regarded
      as the best choice for treating the patient thoroughly. Nowadays such treatment
      is not recommended due to the large cost involved in such treatment. Also,
      removing the patient from a community environment and confining them to an
      institution over a long period is now regarded as discouraging independence.
      Thus, the focus of treatment has shifted from in-patient to out-patient
      treatment. A new model for multi-disciplinary work is now needed because sharing
      patient information between professionals is more difficult at the outpatient
      clinic than on an in-patient ward with shared case notes. In order to make the
      treatment network functional, patients themselves are expected to possess a clear
      understanding of the illness and its treatment. The application of motivational
      enhancement theory is useful in this respect. It is the responsibility of
      psychiatric clinics to encourage the continuous improvement of patient motivation
      for treatment and to make patients tolerant towards changes in treatment
      settings.

PMID- 16999339
TI  - [Intensive psychiatric treatment system for bulimic patients by group therapy].
AB  - Concurrent bulimia nervosa/purging type and anorexia nervosa/binge-purging type
      including binge eating and purging behaviors are considered chronic types of
      eating disorders. The bulimic patients in this study had both these disorders.
      Psychiatric treatment for patients with eating disorders must focus on therapy of
      these bulimic patients, because bulimic patients are more prevalent in the
      psychiatric hospital and clinic, and they have more comorbid psychiatric
      disorders and more other addictive behaviors than other patients with eating
      disorders. We have devised an intensive psychiatric treatment system for bulimic
      patients by group therapy that consists of inpatient treatment, group therapy for
      parents and group rehabilitation. Inpatient treatment, called the Eating
      Disorders Education Program (EDEP), consists of group psychological education,
      group cognitive-behavioral therapy, group nutrition education, and group
      exercise. Group therapy for parents consists of psychological education and group
      meetings. Group rehabilitation consists of many group activities in a house named
      "Mimoza". Bulimic patients come to understand their own disorders and symptoms
      objectively and understand recovery from their disorders by the intensive
      treatment system. Bulimic patients generally recover very slowly from eating
      disorders, but our intensive psychiatric treatment system promotes rapid
      recovery.

PMID- 16999340
TI  - [Cognitive-behavioral therapy for treatment of social anxiety disorder].
AB  - There is good evidence for the effectiveness of exposure-based cognitive
      behavioral therapy (CBT) in the treatment of social anxiety disorder (SAD). In
      this article, the Clark's cognitive model of SAD is presented, followed by the
      description of general CBT strategies, such as the shift from internal to
      external attention and the correction of anticipatory/postevent processing.
      Typical schemata in SAD and comorbid avoidant personality disorder are then
      illustrated, along with schema-focused approaches. Finally, a four-step CBT for
      SAD is suggested.

PMID- 16999341
TI  - [Detection of PTCH gene mutations in odontogenic keratocysts by SSCP and DNA
      sequencing].
AB  - OBJECTIVE: To investigate PTCH gene mutations in odontogenic keratocysts (OKC).
      METHODS: PCR-SSCP and DNA sequencing were used to analyze the PTCH gene mutations
      in 12 OKCs, including 10 sporadic and 2 nevoid basal cell carcinoma syndrome
      (NBCCS) associated OKC. RESULTS: Four mutations were identified in 4 cysts, among
      which two germline mutations were associated with NBCCS and 2 somatic mutations
      were in 2 unrelated sporadic cases. In addition, eight previously reported
      polymorphisms in the PTCH gene were also found in 10 cases. CONCLUSION: The
      present study indicated that both sporadic and NBCCS-related OKCs could carry
      PTCH gene mutation. Thus, mutational inactivation of PTCH gene may play a
      significant role in the pathogenesis of OKC.

PMID- 16999342
TI  - [Effect of overdose fluoride on the expression of enamelin in rat mandibular
      incisor].
AB  - OBJECTIVE: To observe the effect of overdose fluoride on the expression of
      enamelin in rat mandibular incisor. METHODS: Twenty Wistar rats were divided
      randomly into two groups. Animals were maintained in standard environment with
      free access to food and distilled water (control group) or water added with 100
      mg/L F-(experimental group). The rats were killed in the eighth week. HE staining
      was used to observe the morphology of ameloblasts. Immunohistochemical staining
      was adopted to study the expressions of enamelin in rat incisor. RESULTS: The
      ameloblasts of the treated rat were arranged in multi-layer. The ameloblasts in
      group II were thinner than those in group I. The structure of enamel matrix was
      in disorder. The expressions of enamelin in ameloblasts and odontoblasts were
      obviously inhibited in group II (P < 0.01). CONCLUSION: The overdose fluoride
      inhibits the secretion of enamelin and leads to the abnormal development of
      enamel matrix.

PMID- 16999343
TI  - [Expression of human interleukin-1 receptor antagonist in the transfected
      chondrocytes of temporomandibular joint].
AB  - OBJECTIVE: To investigate the expression of the human interleukin-1 receptor
      antagonist (hIL-1ra) in the transfected chondrocytes of temporomandibular joint
      (TMJ). METHODS: Chondrocytes of TMJ in vitro were transfected by hIL-1ra gene via
      cationic liposome as a medium. The stable transfected cells were selected by
      G418. The proliferations of the transduced cell were examined with the growth
      curve, cell population doubling time. The protein expressing in different periods
      was detected by immunocytochemistry and enzyme-linked immunosorbent assay
      (ELISA). RESULTS: The proliferation suppression of gene transfected cells fell
      significantly with compared to normal cells. The expression of hIL-1ra was
      detected in the cell plasma and the cell culture supernatant. The highest
      expression of IL-1ra protein was at the time of 48 hours after gene transfection.
      The transiently transfected cells were secreted IL-1ra protein continuously 28
      days and the stably transduced cells were secreted IL-1ra protein till 72 days.
      CONCLUSION: This study showed that hIL-1ra protein expressed positively in the
      cell plasma and the culture supernatant after gene transfection within a certain
      periods.

PMID- 16999344
TI  - [Preparing of Al2O3/ZrO2 composite dental ceramics through isostatic pressing
      technology].
AB  - OBJECTIVE: To find out how to prepare high-density dental ceramics through
      isostatic pressing so that sintering shrinkage will be reduced. METHODS: To
      prepare Al2O3/ZrO2 composite powder first, then to mold through dry-pressing, and
      to shape the green-body through isostatic pressing. The green-bodies were
      sintered at the temperature of 1 400 degrees C and kept at the temperature for
      different period of time (2 h, 3 h, 4 h). After that, the density and fracture
      strength were measured and the microstructure observed by scanning electron
      microscope (SEM). RESULTS: The sample product's density, line-shrinkage, and
      fracture strength of ceramics was rising with the sintering time lengthened. The
      sample product kept under the temperature of 1 400 degrees C for 4 hours, the
      fracture strength was (497.27 +/- 78.45) MPa and glass phase distributed evenly
      in the ceramics and the grains were integrated owing to the glass phase. The
      longer the sintering time, the more even the microstructure was. CONCLUSION: The
      sintering quality and the efficiency were improved through isostatic pressing.

PMID- 16999345
TI  - [Cyclic fatigue of Vita mark II machinable ceramics under Hertzian's contact].
AB  - OBJECTIVE: To investigate the cyclic fatigue modes of Vita mark II machinable
      ceramics under Hertzian's contact. METHODS: Hertzian's contact technique (WC
      spheres r = 3.18 mm) was used to investigate the cyclic fatigue of Vita mark II
      machinable ceramic. All specimens were fatigued by cyclic loading in moist
      environment, furthermore, surviving strength was examined by three point test and
      morphology damage observation. RESULTS: In homogeneous Vita mark II machinable
      ceramics, two fatigue damage modes existed after cyclic loading with spheres
      under moist environment, including conventional tensile-driven cone cracking
      (brittle mode) and shear-driven microdamage accumulation (quasi-plastic mode).
      The latter generated radial cracks and deeply penetrating secondary cone crack.
      Initial strength degradation were caused by the cone cracks, subsequent and much
      more deleterious loss was caused by radial cracks. CONCLUSION: Cyclic fatigue
      modes of Vita mark II machinable ceramics includes brittle and quasi-plastic
      mode.

PMID- 16999346
TI  - [Use of calcium sulfate as internal matrix to repair furcal perforations].
AB  - OBJECTIVE: To evaluate the effect of internal matrix on sealing ability and
      furcal appearance of perforations repair with amalgam and resin. METHODS:
      Perforations created in the pulpal floor of human extracted molars were repaired
      as follows: Amalgam, amalgam plus calcium sulfate, light-cured resin, and resin
      plus calcium sulfate (15 teeth/group). The furcal appearance of samples was
      evaluated under an operating microscope after repair. With the leakage test
      device, coronal 1 mol/L glucose solution was forced toward the pulpal floor.
      Leakage was measured by the concentration of leaked glucose in bottom reservoir
      at 1, 2, 4, 7, 10, 15 and 20 days with enzymatic glucose oxidase method. RESULTS:
      No significant difference was found between group 1 and group 2 (P > 0.05).
      Leakage in group 4 was obviously lower than group 3 (P < 0.05) after the 7th day.
      CONCLUSION: Calcium sulfate significantly improved the sealing effect of resin
      and provided successful barriers against its overextension.

PMID- 16999347
TI  - [Clinical management of open apices teeth with mineral trioxide aggregate (MTA)
      as apical barrier in adults].
AB  - OBJECTIVE: To evaluate the clinical effect of treatment of open apices teeth with
      mineral trioxide aggregate (MTA) compared with apexification using Vitapex in the
      adult. METHODS: The root canals of 41 anterior teeth and premolars with single
      canal and open apices in adults were cleaned and shaped, and then disinfected
      with calcium hydroxide. The apical root canals of 21 teeth in experimental group
      were filled with MTA to create a 3-5 mm apical barrier. The remainder of the
      canals was filled with AH plus and Obtura II gutta-percha. The canals of 20 teeth
      in control were treated with Vitapex. The root canals were then filled with
      Obtura II gutta-percha when the apical barrier could be detected. The visit
      times, period and result of the treatment were recorded for all cases. RESULTS:
      Good result was achieved in the most cases in the experimental group. The
      postoperative X-ray films showed that the canals of 15 teeth were obturated well.
      6 teeth showed over-filling by 0.5-2 mm. The recalled patients declared their
      teeth to be asymptomatic except one. The recall radiographs indicated that the
      apical radiolucent areas of the teeth with pre-existing apical lesion decreased
      apparently or disappeared completely, except one tooth with large apical
      radiolucency. No new radiolucency was found around the roots. In the control
      group, the apexification of 11 teeth succeeded, and 9 failed. The average visit
      times was 3.5 in experimental group and 6.0 in control. The average period of the
      whole endodontic treatment was 11.8 days in experimental group and 306.8 in
      control. CONCLUSION: MTA is more effective and quicker than apexification in
      treatment of teeth with open apices in adults.

PMID- 16999348
TI  - [Application of the laser welding to preventing the break of the base plate
      caused by the increase of magnetic attachments].
AB  - OBJECTIVE: This study was intended to design a kind of resisting part dint of
      device in order to preventing the base plate break while being subjected to the
      dint when partial base plate dint concentrates because of the increase of the
      magnetic attachment to the original movable artificial teeth. METHODS: Ten
      patients who should increase magnetic attachment was adopted in the study, and we
      increased a kind of new designed partial cast base plate on the original base
      plate using laser welding technique, then designed magnetic attachment and
      artificial teeth. RESULTS: None of ten sufferers appeared the phenomenon of the
      break of the base plate. CONCLUSION: The application of the laser welding
      technique can prevent the break of the base plate when partial dint increase
      because of the increase of the magnetic attachments.

PMID- 16999349
TI  - [Correlation analysis on the malocclusion and articulation of skeletal angle III
      malocclusion in mixed dentition].
AB  - OBJECTIVE: To investigate the effects of skeletal Class III malocclusion in mixed
      dentition on speech articulation and to look for which factors lead to the speech
      errors. METHODS: Thirty-eight children with skeletal Angle Ill malocclusion in
      mixed dentition were selected as a sample group and 40 children with normal
      occlusion in mixed dentition as a control group. Two phoneticians evaluated their
      articulations and wrote down error phonemes respectively. The correlation
      analysis was undertaken between the number of errors and the measurements of
      patients' cephalometry. RESULTS: The number of errors were correlated
      significantly with overbite, UI-LI, OBJ (OB+OJ) and TD-PW. CONCLUSION: There is
      articulatory malfunction in the majority of skeletal Angle III malocclusion
      patients in mixed dentition. Articulatory malfunction is related to the position
      of incisors and the tongue.

PMID- 16999350
TI  - [Morphology of the soft palate in normal humans with digital cephalometry].
AB  - OBJECTIVE: To study the morphology of the soft palate in normal humans with
      digital radiography and to provide the references for therapy of the cleft.
      METHODS: 106 normal people were involved. The morphology of the soft palate was
      observed with digital cephalometry. RESULTS: All static images of soft palate
      could be divided into six types: Shuttle-shaped, crescent-shaped, strip-shaped, S
      shaped, hamulus-shaped and anomalous shaped. The dynamic image was knee-shaped.
      CONCLUSION: The morphology of the soft palate is varied.

PMID- 16999351
TI  - [Reliability evaluation for thirteen parameters describing anteroposterior apical
      base relationship in Angle Class II division 1 patients].
AB  - OBJECTIVE: To study 13 different cephalometric measurements of the
      anteroposterior jaw relationship in Angle Class II division 1 statistically and
      geometrically, and to discuss the effects of various factors on this
      relationship, and then to choose the most adequate measurements. METHODS: 120
      patients with skeletal malocclusion Angle Class II division 1 were selected. The
      samples consisted of 60 men and 60 women between 20 to 28 years of age. Lateral
      cephalometric radiograph for each patient was taken in natural head posture by
      the same operator. A wire plumb line and suspended weight recorded the true
      vertical on each radiograph. The subject was then asked to determine the self
      balanced position of the head. After determining the self-balanced neutral
      position, the subject was asked to look into his/her own eyes in the mirror. ANB
      angle, A-B plane angle, Wits appraisal, AF-BF distance, AXB angle, AB/SN4
      distance, AB/PP distance, AXD angle, AD/SN distance, SGn/AB angle, APDI, FABA
      angle, beta angle and AB/HP distance were measured. Coefficient correlations
      among measurements were tabulated to determine which combination would produce a
      higher value. Fuzzy grouping analysis was made. RESULTS: Statistically
      significant and highly correlated relationships was found among many measurements
      except Wits appraisal and SGn/AB angle. The thirteen measurements could be
      divided into five clusters. CONCLUSION: The cephalometric measurements except
      Wits appraisal and SGn/AB angle can be used to evaluate anteroposterior jaw
      relationship. The AB/SN4 distance is the most adequate measurements. ANB angle, A
      B plane angle, AF-BF distance, AXB angle, AB/PP distance, APDI, FABA angle and
      beta angle are similar in describing anteroposterior apical base relationship in
      Angle Class II division 1 patients.

PMID- 16999352
TI  - [Comparison of color character of VITA shade guide and the custom shade guide].
AB  - OBJECTIVE: To compare the color character of VITA shade guide and the custom
      shade guide with metal substrate. METHODS: Color of 9 sites of 5 series of VITA
      shade guides and custom shade guides with metal substrate were measured by means
      of PR-650 spectrophotometer. RESULTS: The color range of VITA shade guide were
      that L* was 56.86-73.86, a* was-1.29-3.69, b* was 7.09-21.94, and the
      transparence was 3.20-7.59. The color range of the custom shade guide was that L*
      was 60.59-78.54, a* was -1.09-4.99, b* was 7.60-22.35, and the transparence was
      0.23-10.98. L*, a* and b* of the custom shade guide with metal substrate were
      higher than VITA shade guide, and the transparence was differet. The color
      difference of homonymy shade tab between custom shade guide and VITA shade guide
      was larger than 1.5 NBS. CONCLUSION: There is color difference between VITA shade
      guide and custom shade guide. Metal substrate has effects on the color of cero
      metal prosthesis, and color selection in clinic should be carefully considered.

PMID- 16999353
TI  - [Clinic study of root resorption caused by edgewise appliance combined with flat
      bite plate treatment ].
AB  - OBJECTIVE: To study the root resorption caused by edgewise appliance combined
      with flat bite plate treatment. METHODS: 65 patients with edgewise technique and
      flat bite plate treatment were chosen. All patients were taken panoramic
      radiograph before flat bite plate treatment, immediately after flat bite plate
      treatment and 6 months after flat bite plate treatment. Root resorption grade of
      mandibular permanent incisors were analyzed. RESULTS: There were statistical
      difference in the root resorption grade of three groups (P < 0.05), but there was
      no statistical difference between male and female (P > 0.05). CONCLUSION: Flat
      bite plate can cause root resorption of mandibular permanent incisors, but the
      root resorption is slight.

PMID- 16999354
TI  - [Experimental study on ultrasound heating affecting the sensitivity of oral
      carcinoma to chemotherapy drugs].
AB  - OBJECTIVE: To explore the influence of chemosensitivity of Tca8113 cells by
      modified MTT assay after the animal model of Tca8113 were treated by the
      ultrasound hyperthermia. METHODS: The MTT assay of the BALB/C nu/nu mice model of
      Tca8113 cells treated by the ultrasound hyperthermia in vivo was performed.
      RESULTS: The chemosensitivity to the 9 kinds of drugs demonstrated no significant
      differences between the Tca8113 cells in the control group, the 39 degrees C
      treated group and the groups treated from 41 degrees C to 44 degrees C. But
      significant differences between the 40 degrees C-treated group and the 41 degrees
      C or 42 degrees C-treated group existed. In the heating-time grades test, there
      were no significant differences in the chemosensitivity to the 9 kinds of drugs
      between these three pairs of group (the control group and the 15 min-treated
      group, the 30 min-treated and the 45 min-treated group, the 60 min-treated and
      the 75 min-treated group). But there were significant differences between the 30
      min-treated or the 45 min-treated group and the 60 min-treated or the 75 min
      treated group. CONCLUSION: Ultrasound hyperthermia performed in 42 degrees C for
      30-45 min can improve the chemosensitivity of Tca8113 cells to some drugs
      significantly, which confirms the rationality of synchronous combination of
      hyperthermia and chemotherapy in the chemosensitivity point of view for the first
      time.

PMID- 16999355
TI  - [Shaping ability of multi-taper nickel-titanium files in simulated resin curved
      root canal].
AB  - OBJECTIVE: To compare the shaping ability of ISO standard stainless steel K files
      and multi-taper ProTaper nickel-titanium files in simulated resin curved root
      canals. METHODS Thirty simulated resin root canals were randomly divided into
      three groups and prepared by stainless steel K files, hand ProTaper, rotary
      ProTaper, respectively. The amount of material removed from inner and outer wall
      and canal width after canal preparation was measured, while the canal curvature
      before and after canal preparation and canals aberrations were recorded. RESULTS:
      The stainless steel K files removed more material than hand ProTaper and rotary
      ProTaper at the outer side of apex and inner side of curvature (P < 0.05). The
      mean degree of straightening in stainless steel K files group was significantly
      bigger than in ProTaper group (P < 0.05). The canals prepared by ProTaper had no
      evident aberration. CONCLUSION: The shaping ability of ProTaper is better than
      stainless steel K files.

PMID- 16999356
TI  - [Experimental study of the dental follicle's function in tooth root development].
AB  - OBJECTIVE: To study role of dental follicle in tooth root development. METHODS:
      Sixteen mandibular first molar dental germs from eight five-day postnatal Balb/c
      mice were divided into two groups randomly. Dental follicle of germs in one group
      was undetached and that of another group was removed. Subsequently, each of the
      germs was separately transplanted to back-muscles of adult nude mice. At seventh
      and fourteenth day after transplanting, the germs were collected, fixed,
      demineralized, dehydrated, and embedded in wax in sequence. Serial sections of 5
      microm thick were made following the routine methods, stained with haematoxylin
      eosin dying solution, and observed under a light microscope. RESULTS: All
      implantations were located in the back-muscles with abundant capillary
      vasculature. Under microscope, although all tooth germs could further develop
      after grafting, tooth germs without dental follicle developed slowly with small
      size and low calcification compared to those with dental follicle. Although
      position of Hertwig's epithelial root sheath of all germs seemed no changing,
      roots of the group with dental follicle could further develop and the roots
      develop toward the apical direction; this tendency couldn't be seen in the germs
      of another group. Inflammatory cells could be seen in and out of the pulp cavity
      of the two groups at 7th day after grafting, while no obvious inflammatory cell
      was observed at 14th day after grafting. CONCLUSION: Dental follicle play an
      important role in tooth root development. It probably can lead tooth root to
      develop in normal direction.

PMID- 16999357
TI  - [Effect of Yishenqinghuo compound on biological characteristics of rat bone
      marrow stromal cells].
AB  - OBJECTIVE: To evaluate the effect of Yishenqinghuo recipe on biological
      characteristic of rat bone marrow stromal cells (BMSCs) and search for the
      function and mechanism of this recipe in treatment of periodontitis. METHODS: 12-
      to 15-month-old SD rats were allocated into 5 groups. Group A: control group
      (with no periodontitis model, fed with the same dosage of saline as Group D);
      Group B: model group (with periodontitis model, fed with the same dosage of
      saline as Group D); Group C: high dosage group (with periodontitis model, fed
      with a high dosage of medicine); Group D: middle dosage group (with periodontitis
      model, fed with a middle dosage of medicine); and Group E: low dosage group (with
      periodontitis model, fed with a low dosage of medicine). Ten days later, serums
      were collected from all the five groups for in vitro cultivation of BMSCs.
      RESULTS: There was displayed a similarity in effect between the serum collected
      from Group C1 (serum collected 0.5 h after the last gavage of Group C) and that
      from Group A after the last gavage, the effect being the best in terms of
      proliferation of BMSCs. A comparison with the other groups had revealed a
      striking difference (P < 0.01), with Group B having turned out to be the worst.
      The serum from Group C2 (serum collected 1 h after the last gavage of Group C)
      after the last gavage could best enhance the generation and activity of ALP,
      having demonstrated a significant difference (P < 0.01) in comparison with the
      other groups. CONCLUSION: Yishenqinghuo recipe can improve the proliferation of
      BMSCs and facilitate the differentiation to osteoblast.

PMID- 16999359
TI  - [Tension-force induced cyclooxygenase-2 expression mediated by microfilament in
      human periodontal ligament fibroblast].
AB  - OBJECTIVE: To study the role of microfilament polymerization in
      menchanotransduction by human periodontal ligament fibroblast (hPDLFs). METHODS:
      In tension-force group, hPDLFs were treated by tension-force values of 18% for 8
      h, 16 h, 24 h. In tension-force and inhibitor group, the sample was treated with
      5 microg/mL cytochalasin B before using tension-forece. Each sample was collected
      and the expression of cyclooxygenase-2 was measured by using immunohistoche
      staining. RESULTS: In tension-force group, the expression of cyclooxygenase-2
      enhanced with the extension of loading time. In tension-force and inhibitor
      group, cyclooxygenase-2 expression was depressed and had no relation with loading
      time. CONCLUSION: Tension-force induced cyclooxygenase-2 expression is mediated
      by microfilament, disruption of the microfilament polymerization will destroy
      mechanotransduction in hPDLFs.

PMID- 16999358
TI  - [Isolation of bone marrow-derived rat osteoclast-like cells with the digestion of
      trypsin].
AB  - OBJECTIVE: To obtain highly enriched osteoclasts in vitro. METHODS: The bone
      marrow cells of 1-day, 12-day, 24-day and 36-day old Sprague-Dawley (SD) rats
      were separately cultured with the presence of 1,25-(OH)2D3 and dexamethasone, and
      the osteoclast-like cells were identified by Trap staining and scanning electron
      microscope observation and were purified by trypsin digestion. The count of Trap
      positive osteoclast-like cells was analyzed statistically. RESULTS: The
      osteoclast-like cells of each group were Trap positive cells and could form the
      bone absorption lacunas in vitro. The amounts of osteoclast-like cells were
      different statistically between the groups (P < 0.05) except between the groups
      of 1-day old and 12-day old (P > 0.05). Highly enriched osteoclast-like cells
      were harvested by the digestion of 0.25% trypsin and 0.02% EDTA. CONCLUSION: It's
      indicated that a large amount of highly enriched osteoclast-like cells could be
      obtained through the culture of bone marrow cells of 10-day and 12-day old SD
      rats with 1,25-(OH)2D3 and dexamethasone and the digestion of trypsin/EDTA.

PMID- 16999360
TI  - [Experimental studies on ectopic osteogenesis by seeding human mesenchymal stem
      cell on human natural bone derived scaffold materials].
AB  - OBJECTIVE: To investigate the ectopic osteogenesis potential of human natural
      bone derived material combined with human bone marrow mesenchymal stem cells
      (MSCs). METHODS: Cell-scaffold complexes were implanted subcutaneously into the
      left back of the nude mice, and human natural bone derived material were
      implanted into the right back as control group. The mice were killed respectively
      on the postoperative 2 weeks, 4 weeks and 8 weeks. The macroscopic,
      histopathological, alkaline phosphatase (ALP) activity assay methods were
      performed to assess the ectopic osteogenesis potential. RESULTS: The
      cartilaginous osteogenesis were observed in both deproteinated bone and
      decalcified bone, and the more new bone tissue formed gradually as the time went
      by after implantation. ALP activity become stronger followed with the time (P <
      0.05), and compared with the decalcified bone, deproteinated bone displayed
      stronger ALP activity (P < 0.05). CONCLUSION: The MSCs and human natural bone
      derived material can be used as good seed cells and scaffold materials
      respectively to construct tissue-engineered bone, and as the scaffold material,
      deproteinated bone has better osteogenesis ability than decalcifed bone.

PMID- 16999361
TI  - [Study of p16INK4/CDKN2 gene homozygous deletions and point mutation in squamous
      cell carcinoma of buccal mucosa].
AB  - OBJECTIVE: To explore the correlation between homozygous deletions and mutation
      of p16 gene and the carcinogenesis and progression of squamous cell carcinoma of
      buccal mucosa. METHODS: Thirty buccal cancers, 10 leukoplakias and 8 buccal
      mucosas were involved. DNA was extracted from the tissues. PCR was used to
      analyses homozygous deletion of p16 gene. PCR-SSCP-DNA sequencing was performed
      to detect the point mutation of p16 gene. Immunohistochemical techniques were
      used to detect the expression of P16 protein. RESULTS: Gene deletions and point
      mutations were not found in leukoplakia and normal buccal mucosa. Gene deletions
      were found in 7 samples out of 30 cases of squamous cell carcinoma of buccal
      mucosa (23.3%), while point mutations were found in 5 samples out of 30 cases of
      squamous cell carcinoma of buccal mucosa (16.7%). Sequencing analysis showed that
      5 cases point mutations were missense mutations, occurred on exon 2. Three cases
      occurred in the same point, codon 99 (GAT --> AAT). The result of
      immunohistochemical stains showed that 11 out of 12 cases gene inactivation did
      not expressed P16 protein. CONCLUSION: Homozygous deletion and point mutation of
      p16 were the main pattern of gene inactivation in squamous cell carcinoma of
      buccal mucosa. There was a closely correlation between p16 gene inactivation and
      the carcinogenesis of squamous cell carcinoma of buccal mucosa.

PMID- 16999362
TI  - [Association of root canal therapy difficulty with canal anatomic factors in
      mandibular permanent incisors].
AB  - OBJECTIVE: To investigate the association of root canal therapy difficulty with
      canal anatomic factors in Chinese mandibular permanent incisors. METHODS: Two
      hundred and ninety nine Chinese permanent incisors were included in this study.
      The following anatomic items of the root canal were observed: Root canal length,
      number of root canal, morphology, curvature, and calcification of pulp chamber
      and root canal. Based on the root canal therapy evaluation criteria, the root
      canal therapy difficult scores were assessed. The association of root canal
      therapy difficulty with canal anatomic factors was analyzed with logistic
      regression analysis. RESULTS: The root canal therapy difficulty grade I, grade II
      and grade Ill in Chinese mandibular permanent incisors were 29.4%, 20.1% and
      50.5%, respectively. The root canal therapy difficulty was significantly
      associated with the root canal length, number, calcification, and curvature (P <
      0.005). CONCLUSION: The root canal therapy difficulty in Chinese mandibular
      permanent incisor is significantly with root canal anatomy.

PMID- 16999363
TI  - [Homology analysis of the extended-V region of the surface proteins in different
      serotype Streptococcus mutans].
AB  - OBJECTIVE: To analysis the homology among the extended-V region of the surface
      proteins in different serotype Streptococcus mutans (c, f, d, g) and to find out
      it's significance in anti-caries vaccine. METHODS: The DNA of the bacteria
      (standarded serotype c, d, f, g and partial serotype c clinicals) was extracted
      and the extended-V region (SrV+, 1 384-2 514 bp) was amplified using polymerase
      chain reaction (PCR). Then the products were assessed using restriction fragment
      length polymorphism (RFLP) by endonuclease Dde I. The genotypings were sequenced
      and analysised using the program of BLAST on NCBI Gene Bank database. RESULTS:
      About 1.13 kb fragments were produced both in serotype c and f, the serotype d
      and g were failed. The RFLP results showed that five different patterns(A, B, C,
      D, E) among the 117 PCR products were reveled by Dde I. The ration of the
      genotypings A and B were the most among the strains, the C was lower, the D and E
      respectively was 1 and 3 strains per genotype. OMZ175 (serotype f) was belong to
      B genotype. Selected one of the A, B, C genotypings to sequenced and blasted.
      Then the results of the blastn showed that the identities of the gene sequence
      were 92%-98% between the serotype c and serotype f, part sequence of the serotype
      g was homology with the SrV+ of the serotype c, the protein sequence among
      serotype c, d, f, g were 77%-82%. CONCLUSION: It is reasonable to use some
      putative pipetides to study the anti-caries vaccine among the extended-V regions
      of the surface proteins in different serotype (c, d, f, g) in S. mutans.

PMID- 16999364
TI  - [Research of the surface oxide film on anodizing Ni-Cr porcelain alloy].
AB  - OBJECTIVE: To study the shape, thickness and oxide percentage of major metal
      element of oxide film on Ni-Cr porcelain alloy after anodizing pretreatment.
      METHODS: 10 samples were made and divided into 2 groups at random. Then after
      surface pretreatment, the oxide films of two samples of each group were analyzed
      using electronic scanning microscope. The rest 3 samples were measured by X-ray
      photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES). RESULTS:
      Lightly selective solution appeared because the different component parts of the
      alloy have dissimilar electrode, whose dissolve velocity were quite unlike. The
      sample's metal surface expanded, so the mechanical interlocking of porcelain and
      metal increased bond strength. The thickness of oxide film was 1.72 times of the
      control samples. The oxide percentage of major metal elements such as Cr, Ni and
      Mo were higher, especially Cr. It initially involved the formation of a thin
      oxide bound to the alloy and second, the ability of the formed oxide to saturate
      the porcelain, completing the chemical bond of porcelain to metal. CONCLUSION:
      The method of anodizing Ni-Cr porcelain alloy can easily control the forming of
      oxide film which was thin and its surface pattern was uniform. It is repeated and
      a good method of surface pretreatment before firing cycle.

PMID- 16999365
TI  - An eye on the future of rehab.

PMID- 16999366
TI  - A collaborative approach.

PMID- 16999368
TI  - Positron emission tomography in the staging of esophageal cancer.
AB  - Accurate staging of patients with esophageal cancer (EC) is essential for
      selection of appropriate treatment and to predict prognosis. In recent years,
      positron emission tomography using the positron emitting glucose analogue 18F-
      fluorodeoxyglucose (FDG-PET) has emerged as a particularly useful adjunct to
      anatomical imaging modalities as computed tomography (CT) and endoscopic
      ultrasonography (EUS). In the initial staging of EC the additional value of FDG
      PET is its ability to identify distant metastases (stage IV disease), excluding
      patients from unnecessary surgery. The combination of FDG-PET and endoscopic
      ultrasonography with fine-needle aspiration (EUS-FNA) has been suggested as the
      most effective strategy for preoperative EC staging.

PMID- 16999367
TI  - Endoscopic palliation of esophageal cancer.
AB  - Endoscopic palliation is the most suitable approach to improve quality of life in
      patients with esophageal cancer since diagnosis is often made at an advanced
      stage, when radical treatment is unfeasible. Endoscopy offers several techniques
      to palliate dysphagia either by stenting the stenosis or by reducing the tumor
      mass with thermoablation. A small number of randomized controlled trials is
      available to compare the efficacy of different techniques and the ideal
      palliation has not been defined as yet. Recently, the development of self
      expandable covered metal stents has rapidly gained ground in the endoscopy units
      throughout the world as a simple, single step procedure for palliation of
      dysphagia.

PMID- 16999369
TI  - Rehabilitation and quality of life in patients undergoing surgery for esophageal
      cancer.
AB  - The impact of esophageal cancer surgery, postoperatively as well as on quality of
      life (QoL) is still largely unknown. Clinical experience and the scarce existing
      literature concur that these patients show difficulty in returning to their
      original lifestyles and previous social activities, not just due to the
      difficulties common to all tumor pathologies but also for the specific dietary
      and digestive disturbances which characterize esophageal cancer therapy. As
      specific rehabilitation protocols are nonexistent in the literature, in this
      study a rehabilitation planning program, is proposed based on evaluation of
      postoperative and long-term problems which can be tackled with rehabilitation.

PMID- 16999370
TI  - Giant posterior mediastinal liposarcoma invading the esophagus: a case report.
AB  - Giant liposarcoma is an unusual variant of mediastinal tumors. The case of a 73
      year-old woman is reported. She presented with a posterior mediastinal tumor
      invading the third middle tract of the thoracic esophagus and the adventitia of
      the descending aorta, close to the posterior pericardium; a neoplastic thrombus
      2cm in size was located in the upper left pulmonary vein. The tumor was
      completely excised by left thoracotomy, in extracorporeal circulation. The
      postoperative course was uneventful and the patient received adjuvant
      chemotherapy. She is currently alive after 8 months, disease-free. The natural
      history, pathology, and prognosis of the disease are reviewed and management of
      such lesions is discussed.

PMID- 16999371
TI  - Sems (self expanding metal stents) in a patient with esophagogastric cancer and
      esophagorespiratory fistula (ERF).
AB  - Esophagorespiratory fistulas, especially in the upper third of the esophagus, are
      a complication of malignant esophageal tumors, whose management is difficult and
      prognosis is poor. Treatment is palliative and involves restoration of the
      ability to ingest food and prevention of aspiration by insertion of esophageal or
      tracheobronchial stents. In selected patients the insertion of a single stent may
      be insufficient for pallation therefore the placement of parallel stents may be
      indicated in patients with symptoms caused by malignant esophagorespiratory
      fistula. A case of esophagorespiratory fistula managed with insertion of parallel
      stents is presented.

PMID- 16999372
TI  - Role of artificial nutrition in patients undergoing surgery for esophageal
      cancer.
AB  - Malnourished cancer patients undergoing major surgical treatments are at a high
      risk of morbidity and mortality. As compared to patients affected by other
      tumors, the highest rate of malnutrition (78.9%) was found in those with
      esophageal cancer due to postoperative complications. The impact of perioperative
      nutritional support on outcome in esophageal cancer patients undergoing surgery
      is analyzed. Strategies that can be used to preserve or restore the nutritional
      condition in patients throughout treatment are illustrated. Oral supplementation,
      and enteral or parenteral nutrition are among several methods of support. Enteral
      option is to be preferred because the intestinal integrity is preserved, the risk
      of complications is reduced and costs are lower. Prevention or correction of
      nutrient depletion in severely malnourished esophageal cancer patients remarkably
      reduces or eliminates malnutrition-related morbidity and mortality. Therefore to
      identify and treat malnutrition is of the utmost importance.

PMID- 16999373
TI  - Adjuvant chemotherapy in esophageal cancer.
AB  - Esophageal cancer with high incidence and mortality rates plays a major clinical
      and social role. Adjuvant radiotherapy, chemotherapy and combined chemoradiation
      are used for esophageal cancer patients after esophagectomy. Outcomes of these
      approaches are analyzed in the literature. Three randomized clinical trials and
      three retrospective series were reviewed; they provided a representative pattern
      of available data. From their analysis some critical aspects emerged in relation
      to the statistical design of the few, now available randomized clinical trials.
      The number of patients enrolled is too low to verify minimal improvements in
      outcomes. Therefore, to-date there is not definite evidence in the literature
      supporting the role of adjuvant chemotherapy in patients undergoing surgery for
      esophageal cancer.

PMID- 16999374
TI  - Neoadjuvant therapy for esophageal cancer: surgical considerations.
AB  - Esophageal carcinoma is often diagnosed at an advanced, non resectable stage.
      Only early stages show a better prognosis. Surgical treatment represents the gold
      standard. The various surgical techniques do not seem to affect survival. Based
      on the severity of esophageal cancer and on poor outcome achievable with surgery
      alone, multimodality treatments are the most suitable. The possible negative
      impact on the complication rate after neoadjuvant therapy is still debated. Most
      randomized trials have not demonstrated as yet an improvement in prognosis in
      patients undergoing a three-modality treatment. However, patients with complete
      pathologic response after surgical resection were shown to have a better
      prognosis. In conclusion, additional randomized trials are required, aimed at
      evaluating all technical and therapeutic variables which affect prognosis.

PMID- 16999375
TI  - The role of surgical staging in esophageal carcinoma.
AB  - Given the overall poor prognosis of patients with esophageal carcinoma and
      considering the new therapeutic options, surgeons should accurately stage
      patients preoperatively to appropriately tailor their treatment. CT, MRI, PET and
      EUS are still inaccurate in evaluating local surgical resectability and in
      detecting abdominal and thoracic lymph node metastases. Minimally invasive
      surgical staging is a promising adjunct to esophageal cancer staging. The
      thoracoscopic and laparoscopic staging provide more accurate information for
      evaluating local invasion, lymph node and distant metastasis. The greater
      accuracy afforded by minimally invasive staging is essential for patients who
      should undergo radical surgical or multimodal treatment. According to data
      reported by many authors, it seems most useful to combine nonoperative staging
      procedures as CT/MRI and EUS with minimally invasive staging techniques.

PMID- 16999376
TI  - Dysphagia following treatment for esophageal cancer: rehabilitation strategies.
AB  - Dysphagia represents one of the first possible presenting symptoms of tumors of
      the esophagus and is one of the main consequences of surgical intervention
      performed on these tumors. Its treatment is based on accurate evaluation of the
      residual functional deficit (as well as of the possible pre-existing deglutition
      deficit) and on implementing both general and specific rehabilitation treatment.
      These interventions should be carried out by a team of professionals who work
      together in an integrated and coordinated approach to the global caregiving of
      patients undergoing esophagectomy, taking into consideration the diverse physical
      and psychological problems associated with tumor pathology and its treatment
      modality.

PMID- 16999377
TI  - Histopathological classification of esophageal carcinomas.
AB  - Esophageal carcinomas are steadily rising worldwide; they rank sixth among
      tumors. Adenocarcinoma is the most common histological type in Western countries
      while squamous carcinoma is more common in the developing countries. Both types
      are preceded by pre-neoplastic lesions rappresented by Barrett's esophagus for
      adenocarcinoma and low and high grade dysplasia for squamous carcinoma. Some
      continuity exists between dysplastic lesions and frankly invasive tumors.
      Moreover rare hystological types have been described. The surgical pathologist
      plays an important role in evaluating small endoscopic biopsies as well as in
      examining surgical specimens from esophagectomy. In the former case the role is
      exclusively diagnostic while in the latter surgical radicality, cancer stage and
      outcomes of neoadjuvant therapies are assessed. All these data are crucial not
      only for prognosis but also for therapy planning.

PMID- 16999378
TI  - Transhiatal esophagectomy (THE).
AB  - In Transhiatal Esophagectomy(THE) two approaches can be used by the surgeon:
      abdominal and cervical, without thoracotomy. A pioneer of this technique was
      Orringer, with the largest experience world-wide (1085 patients). THE is
      associated with a lower morbidity compared with the transthoracic approach, but
      much controversy exists on whether THE is a suitable operation for cancer,
      because it is not combined with en-bloc lymphadenectomy. However, overall, there
      are no statistical differences between the two. Frequently esophageal carcinoma
      is a systemic disease and thus, the biological behavior and the stage of tumor
      rather than the technique, play a major role.

PMID- 16999379
TI  - Sems (self expanding metal stents) in palliation of esophageal cancer dysphagia.
AB  - Symptomatic inoperable esophageal carcinoma represents a major clinical problem.
      With no treatment, swallowing deteriorates with a dramatic worsening of quality
      of life. At present, self-expanding metal stents (SEMS) are the most effective
      non surgical palliation in inoperable esophageal cancer. The different types of
      available SEMS, techniques, results and complications are discussed.

PMID- 16999380
TI  - Preoperative pulmonary risk assessment in esophagectomy.
AB  - Mortality rate after esophagectomy ranges from 2% to more than 25% and is related
      to preoperative and operative factors. Pulmonary complications are frequently
      seen after esophageal resection with a high mortality rate. The aim of
      preoperative pulmonary risk assessment is to identify patients who can undergo
      esophagectomy evaluating patient-related risk factors and their treatment.
      Preoperative pulmonary risk factors are smoking, respiratory diseases as COPD,
      elderly age and general condition. Careful medical history, physical examination
      and pulmonary function testing contribute to identify risk factors and strategies
      to reduce the risk of pulmonary complications.

PMID- 16999381
TI  - Language delays among foster children: implications for policy and practice.
AB  - This article highlights the centrality of language in early childhood development
      and the potential for language delays to negatively affect long-term outcomes in
      educational and social domains. Given the high rate of language delays in the
      foster care population, an emphasis should be placed on assessing language skills
      among children ages 6 and younger entering foster care. The authors describe
      several existing approaches to assessing language skills and discuss obstacles to
      the widespread implementation of systematic evaluation among foster children.
      Finally, the authors discuss the need for research and programming to establish
      evidence-based practices that encourage the remediation of language delays in
      this highly vulnerable population.

PMID- 16999382
TI  - Foster youth emancipating from care: caseworkers' reports on needs and services.
AB  - This article presents findings from a survey mailed to caseworkers, who answered
      questions about special needs, independent living skills, educational attainment,
      and services for 416 randomly selected foster youth in Illinois. A third of the
      adolescents had a mental health disorder, developmental disability, or other
      special need that their caseworkers believed would interfere with their ability
      to live independently. Additionally, urban youth were underserved relative to
      other youth. Youth with more behavior problems and educational and job skill
      deficits were less likely than other youth to continue to receive child welfare
      services past age 18, suggesting that services must be provided throughout
      adolescence to meet the needs of the most vulnerable clients.

PMID- 16999383
TI  - Enhancing the validity of foster care follow-up studies through multiple alumni
      location strategies.
AB  - While family-based placement prevention services, family reunification programs,
      subsidized guardianship, and aggressive adoption programs are reducing the
      numbers of children spending long periods of time in substitute care, a
      significant number of America's children will come of age in foster care.
      Agencies and policymakers should use research and evaluation to assess the
      effectiveness of foster care in nurturing healthy adults and to explore ways to
      improve services. Outcome studies that have focused on locating and interviewing
      young or middle-aged adults emancipated from foster care have been hampered by
      modest response rates, limiting the field's ability to evaluate the efficacy of
      foster care programs. This article describes a set of strategies that were used
      to achieve higher response rates in two recent follow-up studies.

PMID- 16999384
TI  - The potential for successful family foster care: conceptualizing competency
      domains for foster parents.
AB  - The potential to foster successfully starts with developing and supporting
      competency in 12 domains: providing a safe and secure environment, providing a
      nurturing environment, promoting educational attainment and success, meeting
      physical and mental healthcare needs, promoting social and emotional development,
      supporting diversity and children's cultural needs, supporting permanency
      planning, managing ambiguity and loss for the foster child and family, growing as
      a foster parent, managing the demands of fostering on personal and familial well
      being, supporting relationships between children and their families, and working
      as a team member. This article describes each domain and reviews relevant
      research to help guide the assessment of practicing and future foster parents.

PMID- 16999385
TI  - The economics of adoption of children from foster care.
AB  - Federal initiatives since 1996 have intensified the efforts of states to achieve
      adoption for children in foster care. For many waiting children, the path to
      adoption is long. The authors offer an economic analysis of adoption from foster
      care, with an emphasis on the reasons why achieving the goal of adoption for all
      waiting children may be so difficult. The authors then estimate the determinants
      of adoptions from foster care across the states using data for fiscal years 1996
      and 1997. Adoption assistance subsidy rates stand out as the most important
      determinant of adoptions from foster care, followed by use of alternatives (e.g.,
      intercountry adoption). Adoptive matching on the basis of race does not appear to
      prevent adoptions from foster care in the aggregate, leaving flaws in the
      matching process, such as a lack of information and difficulty using the
      Interstate Compact on the Placement of Children (ICPC), as a primary reason why
      children wait.

PMID- 16999386
TI  - Predictors of running away from family foster care.
AB  - Running away is a frequent but little studied phenomenon among adolescents in
      foster care. Repeated running from care often leads to premature discharge and
      homelessness for youth. This article uses cumulative risk theory in the context
      of normative adolescent development to investigate predicators of running away
      from foster care. Results indicate risks stemming from individual, foster home,
      and child welfare system sources, which offer some insight for prevention and
      intervention.

PMID- 16999387
TI  - Enhancing the safety of children in foster care and family support programs:
      automated critical incident reporting.
AB  - The Adoption and Safe Families Act of 1997 has made child safety an explicit
      focus in child welfare. The authors describe an automated critical incident
      reporting program designed for use in foster care and family-support programs.
      The program, which is based in Lotus Notes and uses e-mail to route incident
      reports from direct service staff to supervisors and administrators, facilitates
      timely clinical oversight and risk management and ensures the security of
      clients' protected health information. The authors present data collected using
      the program to illustrate how it can be used to monitor abuse and neglect
      allegations in a foster care program. A survey of users found that the program
      saved time, was easy to use, and helped manage critical incident reports.

PMID- 16999388
TI  - Behavioral health service use and costs among children in foster care.
AB  - This article compares behavioral health service use and cost for foster care
      versus nonfoster care children; children before, during, and after foster care
      placement; and successfully reunified versus nonsuccessfully reunified foster
      care children. Behavioral health service costs for children in foster care were
      higher than for children not in foster care. Children in foster care used more
      services during their foster care placement than before placement and after
      discharge. Nonsuccessfully reunified children received a significantly larger
      quantity of services than those successfully reunified.

PMID- 16999389
TI  - Extended calix[4]arene analogues by two P-CuI-P bridges and anion encapsulation.
AB  - Two novel extended calix[4]arene analogues by two P-Cu(I)-P bridges have been
      synthesized. The molecular structures and anion encapsulation ability for ClO4-
      and BF4- have been studied by X-ray analysis.

PMID- 16999390
TI  - New porphyrin-based metal-organic framework with high porosity: 2-D infinite 22.2
      A square-grid coordination network.
AB  - A new 2-D coordination network with 22.2-A square-grid coordination networks was
      prepared from a dicopper(II) tetraacetate [Cu2(AcO)4] as a linear linker motif
      and 5,10,15,20-tetra-4-pyridyl-21H,23H-porphine (H2TPyP) as a four-connected
      vertex, forming a regular high-porous structure. The characterization by N2
      adsorption indicated that this coordination network has uniform micropores and
      gas adsorption cavities.

PMID- 16999391
TI  - Steric control of a bridging ligand for high-nuclearity metallamacrocycle
      formation: a highly puckered 60-membered icosanuclear metalladiazamacrocycle.
AB  - A novel S4-symmetric icosanuclear manganese metalladiazamacrocycle was
      synthesized using a pentadentate ligand, N-3-phenyl-trans-2
      propenoylsalicylhydrazide (H3L), that has a rigid and bulky terminal N-acyl
      group. A 20 cyclic repeat of an--(Mn-N-N)--linkage resulted in a highly puckered
      diaza-bridged 60-membered icosanuclear metallamacrocycle. The steric interaction
      between the ligands in the cyclic system leads to five consecutive Mn(III)
      centers in a chemically different--(Mn(A)Mn(B)Mn(C)Mn(D)Mn(E))--environment, with
      the chiralities of the metal centers being in a rather complicated-
      (LambdaLambdaDeltaLambdaLambda)(DeltaDeltaLambdaDeltaDelta)--sequence.

PMID- 16999392
TI  - Cu(NO3)2.3H2O-mediated synthesis of 4'-(2-pyridyl)-2,2':6',2' '-terpyridine (L2)
      from N-(2-pyridylmethyl)pyridine-2-methylketimine (L1). A C-C bond-forming
      reaction and the structure of {[Cu(L2)(OH)(NO3)][Cu(L2)(NO3)2]}.2H2O.
AB  - N-(2-Pyridylmethyl)pyridine-2-methylketimine (L1) was synthesized from equimolar
      quantities of (2-pyridyl)methylamine and 2-acetylpyridine. Methanolic solution of
      L1 reacted readily with Cu(NO3)2.3H2O in air, affording green solid of
      composition {[Cu(L2)(OH)(NO3)][Cu(L2)(NO3)2]}.2H2O, where L2 is 4'-(2-pyridyl)
      2,2':6',2' '-terpyridine. Oxidation of the active methylene group of L1 to an
      imide and then condensation with 2-acetylpyridine involving a C-C bond-forming
      reaction, mediated by a Cu2+ ion, are the essential steps involved in the
      conversion of L1 to L2. L2 is isolated by extrusion of Cu2+ with EDTA(2-). The
      copper center in [Cu(L2)(OH)(NO3)] has a mer-N3O3 environment, and that in
      [Cu(L2)(NO3)2] has a distorted trigonal-bipyramidal geometry. Two H2O molecules
      held by C-H...O interactions are present in the predominantly hydrophobic
      channels of approximate cavity dimension 7.60 x 6.50 A created by aromatic rings
      through pi-pi interactions.

PMID- 16999393
TI  - Synthesis of the first rNHC (remote N-heterocyclic carbene) complexes with no
      heteroatom in the carbene carbon-containing ring.
AB  - Two cationic carbene complexes with no heteroatom in the ring containing the
      carbene carbon, trans-bromo(2-methyl-2,6-dihydroisoquinolin-6
      ylidene)bis(triphenylphosphine)palladium(II) triflate (3) and trans-chloro(1,2
      dimethyl-1,7-dihydroquinolin-7-ylidene)bis(triphenylphosphine)palladium(II)
      triflate (4), were synthesized by oxidative substitution of Pd(PPh3)4 with N
      methylated 6-bromoisoquinolinium and 7-chloro-2-methylquinolinium cations,
      respectively. Compound 3 was also prepared by methylation of neutral trans
      bromo(2-methylisoquinolin-6-yl)bis(triphenylphosphine)palladium(II) (5). All
      complexes were unambiguously characterized by NMR and X-ray crystallographic
      studies.

PMID- 16999394
TI  - Active-site models for iron hydrogenases: reduction chemistry of dinuclear iron
      complexes.
AB  - Reduction of Fe2(mu-S2C3H6)(CO)6 (1) in tetrahydrofuran with 1 equiv of
      decamethylcobaltocene (Cp*2Co) affords a tetranuclear dianion 2. The IR spectra
      of samples of 2 in solution and in the solid state exhibit a band at 1736 cm(-1),
      suggestive of the presence of a bridging carbonyl (CO) ligand. X-ray
      crystallography confirms that the structure of 2 consists of two Fe2 units
      bridged by a propanedithiolate moiety formulated as [Fe2(mu
      S2C3H6)(CO)5(SCH2CH2CH2-mu-S)Fe2(mu-CO)(CO)6](2-). One of the Fe2 units has a
      bridging CO ligand and six terminal CO ligands. The second subunit exhibits a
      bridging propanedithiolate moiety. One CO ligand has been replaced by a terminal
      thiolate ligand, replicating the basic architecture of Fe-only hydrogenases. The
      reduction reaction can be reversed by treatment of 2 with 2 equiv of
      [Cp2Fe][PF6], reforming complex 1 in near-quantitative yield. Complex 2 can also
      be oxidized by acids such as p-toluenesulfonic acid, regenerating complex 1 and
      forming H2.

PMID- 16999395
TI  - Self-assembly of the 2-His-1-carboxylate facial triad in mononuclear iron(II) and
      zinc(II) models of metalloenzyme active sites.
AB  - A synthetic strategy involving the use of sterically hindered N-donor and
      terphenylcarboxylate ligands has been used to prepare complexes of iron(II) and
      zinc(II) that feature N2(carboxylate) donors. X-ray crystallographic and NMR data
      show that the 2-His-1-carboxylate facial triad found in metalloenzyme active
      sites is closely modeled by the mononuclear complexes. In addition, by virtue of
      the flexibility of the ligands used, the geometries and coordination environments
      of the complexes display carboxylate binding mode differences such as those seen
      in the enzymes.

PMID- 16999396
TI  - Mononitrosyl iron complexes supported by sterically hindered carboxylate ligands.
AB  - Complexes that feature a single NO bound to Fe, as postulated in various
      carboxylate-rich metalloproteins, were prepared by mixing Fe(II) salts, NO, and
      the sterically encumbered 2,6-dimesitylbenzoate (Mes2ArCO2-). Among the compounds
      isolated are the potentially useful heterobimetallic synthon Tl(mu
      Mes2ArCO2)3Fe(NO) and a novel cubane Fe4(Mes2ArCO2)4(NO)4(mu3-OH)4 that forms in
      the presence of added H2O and features syn-[FeNO]2 units.

PMID- 16999397
TI  - electrochemical generation of a nonheme oxoiron(IV) complex.
AB  - The complex [Fe(IV)O(N4Py)]2+ (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2
      pyridyl)methylamine) has been prepared by bulk electrolysis in aqueous CH3CN and
      CH2Cl2, and its redox properties characterized. Bulk chronocoulometry and
      spectropotentiometry experiments in CH3CN show that [Fe(II)(N4Py)(NCCH3)]2+ can
      be oxidized quantitatively to its iron(III) derivative at an applied potential of
      +0.71 V vs ferrocene and then to the oxoiron(IV) complex (in the presence of
      added water) at potentials above +1.3 V. The E1/2 value for the Fe(IV/III) couple
      has been estimated to be +0.90 V from spectropotentiometric titrations in CH3CN
      and cyclic voltammetric measurements in CH2Cl2.

PMID- 16999399
TI  - Coordination modes in the formation of the ternary Am(III), Cm(III), and Eu(III)
      complexes with EDTA and NTA: TRLFS, 13C NMR, EXAFS, and thermodynamics of the
      complexation.
AB  - The formation and the structure of the ternary complexes of trivalent Am, Cm, and
      Eu with mixtures of EDTA+NTA (ethylenediamine tetraacetate and nitrilotriacetate)
      have been studied by time-resolved laser fluorescence spectroscopy, 13C NMR,
      extended X-ray absorption fine structure, and two-phase metal ion equilibrium
      distribution at 6.60 m (NaClO4) and a hydrogen ion concentration value (pcH)
      between 3.60 and 11.50. In the ternary complexes, EDTA binds via four
      carboxylates and two nitrogens, while the binding of the NTA varies with the
      hydrogen ion concentration, pcH, and the concentration ratios of the metal ion
      and the ligand. When the concentration ratios of the metal to ligand is low
      (1:1:1-1:1:2), two ternary complexes, M(EDTA)(NTAH)(3-) and M(EDTA)(NTA)(4-), are
      formed at pcH ca. 9.00 in which NTA binds via three carboxylates, via two
      carboxylates and one nitrogen, or via two carboxylates and a H2O. At higher
      ratios (1:1:20 and 1:10:10) and pcH's of ca. 9.00 and 11.50, one ternary complex,
      M(EDTA)(NTA)(4-), is formed in which NTA binds via three carboxylates and not via
      nitrogen. The two-phase equilibrium distribution studies at tracer concentrations
      of Am, Cm, and Eu have also confirmed the formation of the ternary complex
      M(EDTA)(NTA)(4-) at temperatures between 0 and 60 degrees C. The stability
      constants (log beta111) for these metal ions increase with increasing
      temperature. The endothermic enthalpy and positive entropy indicated a
      significant effect of cation dehydration in the formation of the ternary
      complexes at high ionic strength.

PMID- 16999398
TI  - Spectroscopic methods in bioinorganic chemistry: blue to green to red copper
      sites.
AB  - A wide variety of spectroscopic methods are now available that provide
      complimentary insights into the electronic structures of transition-metal
      complexes. Combined with calculations, these define key bonding interactions,
      enable the evaluation of reaction coordinates, and determine the origins of
      unique spectroscopic features/electronic structures that can activate metal
      centers for catalysis. This presentation will summarize the contributions of a
      range of spectroscopic methods combined with calculations in elucidating the
      electronic structure of an active site using the blue copper site as an example.
      The contribution of electronic structure to electron-transfer reactivity will be
      considered in terms of anisotropic covalency, electron-transfer pathways,
      reorganization energy, and protein contributions to the geometric and electronic
      structures of blue-copper-related active sites.

PMID- 16999400
TI  - Two-dimensional lanthanide heteropolyvanadates of manganese(IV) and nickel(IV)
      containing two types of heteropoly anions with 1:13 and 1:12 stoichiometry.
AB  - Reactions of 1:13 heteropoly anions [MV13O38](7-) (M = Mn, Ni) and lanthanide
      cations Ln3+ (Ln = La, Ce, or Pr) produce five isomorphic compounds, which are
      crystallized in the triclinic crystal system, space group P1, and formulated as
      [Ln6(H2O)25(MV12O38)(HMV13O38)].nH2O ((1) Ln = La, M = Mn, and n approximately
      31; (2) Ln = Ce, M = Mn, and n approximately 29; (3) Ln = Pr, M = Mn, and n
      approximately 31; (4) Ln = La, M = Ni, and n approximately 28; (5) Ln = Pr, M =
      Ni, and n approximately 33). These compounds are two-dimensional polymeric
      structures constructed by hydrated lanthanide cations and two types of heteropoly
      anions, [MV13O38](7-) and [MV12O38](12-). In contrast to the previous reported
      1:13 heteropoly anions, all with disordered structures, [MV13O38](7-) clusters in
      1-5 are non-disordered with a distinct mode. The second kind of anionic cluster
      [MV12O38](12-) with O(h) symmetry, which consists of 13 entire edge-sharing MO(6)
      (M = V, Mn or Ni) octahedra, has not been reported hitherto. The emergence of the
      new cluster may be correlated to the six capping lanthanide cations surrounding
      it with a stabilization effect. In this paper, the syntheses and structures of
      the five polymeric lanthanide heteropolyvanadates of manganese(IV) and nickel(IV)
      have been presented.

PMID- 16999401
TI  - Neutral Ru(II)-based emitting materials: a prototypical study on factors
      governing radiationless transition in phosphorescent metal complexes.
AB  - In addition to the metal-centered dd transition that is widely accepted as a
      dominant radiationless decay channel, other factors may also play important roles
      in governing the loss of phosphorescence efficiency for heavy-transition-metal
      complexes. To conduct our investigation, we synthesized two dicarbonylruthenium
      complexes with formulas [Ru(CO)2(BQ)2] (1) and [Ru(CO)2(DBQ)2] (2), for which the
      cyclometalated ligands BQ and DBQ denote benzo[h]quinoline and
      dibenzo[f,h]quinoxaline, respectively. Replacing one CO ligand with a P donor
      ligand such as PPh2Me and PPhMe2 caused one cyclometalated ligand to undergo a
      180 degrees rotation around the central metal atom, giving highly luminous metal
      complexes [Ru(CO)L(BQ)2] and [Ru(CO)L(DBQ)2], where L = PPh2Me and PPhMe2 (3-6),
      with emission peaks lambda(max) in the range of 571-656 nm measured in the fluid
      state at room temperature. It is notable that the S0-T1 energy gap for both 1 and
      2 is much higher than that of 3-6, but the corresponding phosphorescent spectral
      intensity is much weaker. Using these cyclometalated Ru metal complexes as a
      prototype, our experimental results and theoretical analysis draw attention to
      the fact that, for complexes 1 and 2, the weaker spin-orbit coupling present
      within these molecules reduces the T1-S0 interaction, from which the thermally
      activated radiationless deactivation may take place. This, in combination with
      the much smaller 3MLCT contribution than that observed in 3-6, rationalizes the
      lack of room-temperature emission for complexes 1 and 2.

PMID- 16999402
TI  - Synthesis, characterization, and solution properties of a novel cross-bridged
      cyclam manganese(IV) complex having two terminal hydroxo ligands.
AB  - A novel monomeric tetravalent manganese complex with the cross-bridged cyclam
      ligand 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (Me2EBC),
      [Mn(IV)(Me2EBC)(OH)2](PF6)2, was synthesized by oxidation of Mn(II)(Me2EBC)Cl2
      with H2O2 in the presence of NH4PF6)in aqueous solution. The X-ray crystal
      structure determination of this manganese(IV) compound revealed that it contains
      two rare terminal hydroxo ligands. EPR studies in dry acetonitrile at 77 K show
      two broad resonances at g = 1.96 and 3.41, indicating that the manganese(IV)
      exists as a high-spin d3 species. Resonance Raman (rR) spectra of this
      manganese(IV) species reveal that the dihydroxy moiety, Mn(IV)(OH)2, is also the
      dominant species in aqueous solution (pH < 7). pH titration provides two pK(a)
      values, 6.86(4) and 10.0(1), associated with stepwise removal of the last two
      oxygen-bound protons from [Mn(IV)(Me2EBC)(OH)2](2+). The cyclic voltammetry of
      this manganese(IV) complex in dry acetonitrile at 298 K demonstrates two
      reversible redox processes at +0.756 and -0.696 V (versus SHE) for the Mn4+/Mn3+
      and Mn3+/Mn2+ couples, respectively. This manganese(IV) complex is relatively
      stable in weak acidic aqueous solution but easily degrades in basic solution to
      manganese(III) derivatives with an 88 +/- 1% yield.

PMID- 16999403
TI  - Organic-inorganic hybrid compounds of Li with bisimidazole derivatives: Li ion
      binding study and topochemical properties.
AB  - The imidazole-based ligands, bis(imidazol-1-yl)methane (Bizm, 1a) and
      (pyrenyl)bis(imidazol-1-yl) methane (Pbizm,2a) were prepared. With LiClO4, these
      two compounds formed two novel organic-inorganic hybrid materials: a 3D network
      polymer Li(Bizm).ClO4 (1b) and a 1D chain polymer Li(Pbizm)2.ClO4 (2b). The
      intriguing topological and physiochemical characteristics of 1b and 2b are
      reported on the basis of the X-ray single-crystal structure analysis and Li ion
      binding studies.

PMID- 16999404
TI  - CH...pi interaction for rhenium-based rectangles: an interaction that is rarely
      designed into a host-guest pair.
AB  - Alkoxy- and thiolato-bridged Re(I) molecular rectangles [{(CO)3Re(mu
      ER)2Re(CO)3}2(mu-bpy)2] (ER = SC4H9, 1a; SC8H17, 1b; OC4H9, 2a; OC12H25, 2b; bpy
      = 4,4'-bipyridine) exhibit strong interactions with several planar aromatic
      molecules. The nature of their binding was studied by spectral techniques and
      verified by X-ray diffraction analysis. Standard absorption and fluorescence
      titrations showed that a relatively strong 1:1 interaction occurs between
      aromatic guests such as pyrene and these rectangles. The results of a single
      crystal X-ray diffraction analysis show that the recognition of 1 with a pyrene
      molecule is mainly due to CH...pi interactions and the face of the guest pyrene
      is located over the edges of the bpy linkers of 1. This is a fairly novel example
      of an interaction that is rarely designed into a host-guest pair. Furthermore,
      the interaction of 1 with Ag+ results in the self-organization of supramolecular
      arrays, as revealed by solid-state data.

PMID- 16999405
TI  - Novel Ti-O-Ti bonding species constructed in a metal-oxide cluster: reaction
      products of bis(oxalato)oxotitanate(IV) with the dimeric, 1,2-dititanium(IV)
      substituted Keggin polyoxotungstate.
AB  - The preparation and structural characterization of a novel Ti-O-Ti bonding
      complex constructed in a dilacunary alpha-Keggin polyoxometalate (POM),
      [[{Ti(ox)(H2O)}4(mu-O)3](alpha-PW10O37)](7-) (H2ox = oxalic acid) (1a), are
      described. The water-soluble, crystalline complex with a formula of
      K6H[1a].0.5KCl.10H2O (1p) was prepared as the bulk sample in 28.0% (0.51 g scale)
      yield in a 1:4 molar-ratio reaction of the dititanium(IV)-substituted, dimeric
      form of an alpha-Keggin POM, K10[(alpha-1,2-PW10Ti2O39)2].18H2O, with the
      titanium(IV) source K2[TiO(ox)2].2H2O in HCl-acidic solution (pH 0.08). Prior to
      formation of 1p, the KCl-free crystalline compound (1c) obtained was
      characterized with X-ray crystallography. The compound 1p was unequivocally
      characterized with complete elemental analysis, thermogravimetric and
      differential thermal analyses (TG/DTA), FTIR, and solution (31P, 183W, and 13C)
      NMR spectroscopy. The molecular structure of 1a was determined. The POM 1a in the
      solid state was composed of the four octahedral Ti groups (four guests), i.e.,
      the two Ti-O-Ti groups linked with the mu-O atom, incorporated to the two
      adjacent, octahedral vacant sites (two hosts) in the dilacunary Keggin POM. The
      formation of 1a, as well as the recently found POM [{Ti(ox)(H2O)}2(mu-O)](alpha
      PW11O39)](5-) (2a), was strongly dependent on the reaction with [TiO(ox)2](2-),
      i.e., the anionic titanium(IV) complex as the titanium(IV) source. The POM 1a is
      contrasted to most titanium(IV)-substituted POMs consisting of a combination of a
      monolacunary site (one host) and an octahedral Ti group (one guest) and also
      contrasted to 2a as a combination of a monolacunary site (one host) and two
      octahedral Ti groups or a Ti-O-Ti group (two guests).

PMID- 16999406
TI  - Spectroscopic and potentiometric characterization of oxovanadium(IV) complexes
      formed by 3-hydroxy-4-pyridinones. Rationalization of the influence of basicity
      and electronic structure of the ligand on the properties of V(IV)O species in
      aqueous solution.
AB  - Aqueous solution studies regarding the identification and characterization of
      complexes formed by the VIVO ion and 11 3-hydroxy-4-pyridinone derivatives have
      been performed using EPR and UV/vis spectroscopic techniques. For the three
      ligands (HL) adequately soluble in water (1-methyl-3-hydroxy-4-pyridinone, 1
      methyl-2-ethyl-3-hydroxy-4-pyridinone, and 1,2-diethyl-3-hydroxy-4-pyridinone),
      potentiometric titrations were performed; the results are consistent with the
      formation of [V(IV)OL]+, [V(IV)OL2], [V(IV)OL2H(-1)]-, [(V(IV)O)2L2H(-2)], and
      [V(IV)L3]+ species. Bis chelated complexes are characterized by a cis-trans
      isomerism, the trans isomer being strongly favored with respect to the cis
      arrangement. Tris chelated non-oxo V(IV) species were prepared in CH3COOH; their
      spectroscopic features point to a d(z2) ground state and a geometry intermediate
      between an octahedron and a trigonal prism, related to the steric requirements of
      the substituent on the carbon atom in position 2 of the pyridinone ring. Four new
      solid derivatives, [V(IV)O(1,2-diethyl-3-hydroxy-4-pyridinonato)2], [V(IV)O(1-(p
      tolyl)-2-ethyl-3-hydroxy-4-pyridinonato)2], [V(IV)O(1-(p-(n-butyl)phenyl)-2-ethyl
      3-hydroxy-4-pyridinonato)2], and [V(IV)O(1-(p-(n-hexyl)phenyl)-2-ethyl-3-hydroxy
      4-pyridinonato)2], were isolated and characterized; they exhibited a five
      coordinate geometry close to square-pyramid. A criterion for establishing the
      degree of distortion toward the trigonal-bipyramid on the basis of the electronic
      absorption spectra is provided. Relationships between the pKa of the -OH group in
      position 3 of the ring and (i) log K of mono and bis chelated complexes, (ii) pK
      of the water molecule in cis-[V(IV)OL2(H2O)], (iii) log K of tris chelated
      species [V(IV)L3]+, and (iv) 51V hyperfine coupling constant (Az) have been
      established and discussed for a number of pyrone, pyridinone, and catechol
      ligands. The results are rationalized by assuming for pyridinones an electronic
      structure intermediate between that of pyrones and catechols. The relationships
      are valuable to the understanding of the behavior of VIVO species in aqueous
      solution.

PMID- 16999407
TI  - Cadmium(II) and copper(II) complexes with imidazole-containing tripodal polyamine
      ligands: pH and anion effects on carbon dioxide fixation and assembling.
AB  - A new Cd(II) complex [Cd3(L)3(mu3-CO3)](ClO4)4.2CH3CN (1) with two-dimensional
      (2D) network structure was obtained by reaction of an imidazole-containing
      tripodal polyamine ligand N1-(2-aminoethyl)-N1-(2-imidazolethyl)-ethane-1,2
      diamine (L) with Cd(ClO4)2.6H2O at pH 9.0 in air. The carbonate anions (CO3(2-))
      are from the hydration of the atmospheric carbon dioxide, which is the same as in
      the previously reported Cu(II) complex [Cu3(L)3(mu3-CO3)](ClO4)4.3CH3CN (2).
      However, the coordination mode of CO3(2-) in 1 is mu3-eta2:eta2:eta2 while the
      one in 2 is mu3-eta1:eta1:eta1. One-dimensional (1D) chain Cd(II) and Cu(II)
      complexes [Cd(L)Cl]ClO4.H2O (3) and [Cu(L)(H2O)](ClO4)2 (4) without CO3(2-) were
      prepared by a similar method as that for 1 and 2 except for the different
      reaction pH, namely, 3 and 4 were obtained at pH 7 while 1 and 2 were obtained at
      pH 9. In addition, when Cu(NO3)2 was used to react with L at pH 9, a unique 1D
      double-stranded helical chain complex [Cu(L)Cl]NO3.1.25H2O (5) was obtained. The
      results revealed that the reaction pH and the counteranion have great impact on
      the carbon dioxide absorption and hydration as well as on the assembling and
      structure of the complexes. The magnetic property of complex 2 was investigated
      in the temperature range of 1.8-300 K, and weak ferromagnetic coupling among the
      mu3-eta1:eta1:eta1-CO3(2-) bridged Cu(II) atoms was observed.

PMID- 16999408
TI  - Syntheses and X-ray crystal structures of zirconium(IV) and hafnium(IV) complexes
      containing monovacant wells-Dawson and Keggin polyoxotungstates.
AB  - The syntheses and crystal structures of a series of zirconium(IV) and hafnium(IV)
      complexes with Dawson monovacant phosphotungstate [alpha2-P2W17O61](10-) and in
      situ-generated Keggin monovacant phosphotungstate [alpha-PW11O39](7-), which was
      obtained by a reaction of [alpha-PW12O40](3-) with Na2CO3, are described.
      K15H[Zr(alpha2-P2W17O61)2].25H2O (K-1), K16[Hf(alpha2-P2W17O61)2].19H2O (K-2),
      (Et2NH2)10[Zr(alpha-PW11O39)2].7H2O (Et2NH2-3), and (Et2NH2)10[Hf(alpha
      PW11O39)2].2H2O (Et2NH2-4), being afforded by reactions in aqueous solutions of
      monolacunary Dawson and Keggin polyoxotungstates with ZrCl2O.8H2O and HfCl2O.8H2O
      followed by exchanging countercations, were obtained as analytically pure,
      homogeneous colorless crystals. Single-crystal X-ray structure analyses revealed
      that the Zr(IV) and Hf(IV) ions are in a square antiprismatic coordination
      environment with eight oxygen atoms, four of them being provided from each of the
      two monovacant polyanion ligands. Although the total molecular shapes and the 8
      coordinate zirconium and hafnium centers of complexes 1-4 are identical, the
      bonding modes (bond lengths and bond angles) around the zirconium(IV) and
      hafnium(IV) centers were dependent on the monovacant structures of the polyanion
      ligands. Additionally, the characterization of complexes 1-4 was accomplished by
      elemental analysis, TG/DTA, FTIR, and solution (31P and 183W) NMR spectroscopy.

PMID- 16999409
TI  - Two mixed-valence vanadium(III,IV) phosphonoacetates with 16-ring channels:
      H2(DABCO)[V(IV)O(H2O)V(III)(OH)(O3PCH2CO2)2].2.5H2O and
      H2(PIP)[V(IVO)(H2O)V(III)(OH)(O3PCH2CO2)2].2.5H2O.
AB  - Two isostructural mixed-valence vanadium phosphonoacetates
      H2(DABCO)[V(IV)O(H2O)V(III)(OH)(O3PCH2CO2)2].2.5H2O (1) and
      H2(PIP)[V(IV)O(H2O)V(III)(OH)(O3PCH2CO2)2].2.5H2O (2) have been synthesized. They
      crystallize in the orthorhombic space group Pnna with a = 7.0479(10) A, b =
      15.307(2) A, and c = 17.537(3) A for 1 and a = 7.0465(9) A, b = 15.646(2) A, and
      c = 17.396(2) A for 2. X-ray single-crystal diffraction reveals that 1 and 2 have
      a three-dimensional open framework featuring 16-ring ellipsoid channels that are
      filled with doubly protonated 1,4-diazabicyclo[2,2,2]octanium/piperazinium
      cations and water molecules. According to the classification in metal-organic
      frameworks, 1 and 2 contain infinite (-O-V-)(infinity) chains that are cross
      linked by "metalloligand" [VO(H2O)(O3PCH2CO2)2](4-) into a 3-D net of the sra
      topology. The temperature dependence of the magnetic susceptibility of 1 shows
      that the chi(m)T value in the range of 60-320 K is constant of 1.105 cm3 K mol(
      1)/V2 unit, and upon further cooling, the chi(m)T value rapidly increases to 1.81
      cm3 K mol(-1) at 2 K. The corresponding effective magnetic moment (mu(eff))/V2
      unit varies from 2.97 mu(B) at 320 K to 3.80 mu(B) at 2 K. The magnetic data in
      the range of 2-320 K follow the Curie-Weiss law with C = 1.074 cm3 K mol(-1) and
      Theta= -1.34 K.

PMID- 16999410
TI  - Structural-electronic correlation in the first-order phase transition of [FeH2L2
      Me](ClO4)2 (H2L2-Me = bis[((2-methylimidazol-4-yl)methylidene)-3-
      aminopropyl]ethylenediamine).
AB  - The synthesis and detailed study of the new mononuclear spin crossover complex
      [Fe(II)H2L(2-Me)](ClO4)2 (where H2L(2-Me) = bis[((2-methylimidazol-4
      yl)methylidene)-3-aminopropyl]ethylenediamine) are reported. Variable-temperature
      magnetic susceptibility measurements show the occurrence of a steep spin
      crossover centered at 171.5 K with a hysteresis loop of ca. 5 K width
      (T(/2)(increasing) = 174 K and T(1/2)(decreasing) = 169 K, for increasing and
      decreasing temperatures, respectively). The crystal structure has been resolved
      for the high-spin (HS) and low-spin (LS) states at 200 and 123 K, respectively,
      revealing a crystallographic phase transition that occurs concomitantly to the
      spin crossover: at 200 K, the complex crystallizes in the monoclinic system,
      space group P2(1)/n, while the space group is P2(1) at 123 K. The mean Fe-N
      distances are shortened by 0.2 A, but the thermal spin crossover is accompanied
      by significant structural changes: the rearrangement of the central atom C12 of a
      six-membered chelate ring of [Fe(II)H2L(2-Me)]2+ to two positions (C12A and C12B)
      and, consequently, the lack of an inversion center at 123 K (P2(1) space group).
      Both HS and LS supramolecular structures involve all possible hydrogen bonds
      between imidazole and amine NH functions, and perchlorate anions; however, the HS
      supramolecular structure is a one-dimensional (1D) network, and the LS phase may
      better be described as a two-dimensional (2D) extended structure of A and B
      molecules. The structural phase transition of [FeH2L(2-Me)](ClO4)2 seems to
      trigger the steep and hysteretic spin crossover. Discontinuities in the
      temperature dependence of the Mossbauer parameters (isomer shift and quadrupole
      splitting) at the spin crossover temperature confirmed the occurrence of a
      structural phase transition. The experimental enthalpy and entropy variations
      were determined by differential scanning calorimetry (DSC) as 7.5 +/- 0.4 kJ/mol
      and 45 +/- 3 J K(-1) mol(-1), respectively. The regular solution theory was
      applied to the experimental data, yielding an interaction parameter of Gamma =
      3.36 kJ/mol, which is larger than 2RT(1/2), which fulfills the condition for
      observing hysteresis.

PMID- 16999411
TI  - Structural and electrochemical investigations of the high fluoride affinity of
      sterically hindered 1,8-bis(boryl)naphthalenes.
AB  - The reaction of 10-bromo-9-oxa-10-boraanthracene with the
      tetrakis(tetrahydrofuran)lithium salt of dimesityl-1,8-naphthalenediylborate in
      diethyl ether affords 1-(dimesitylboryl)-8-(10'-bora-9'-oxaanthryl)naphthalene
      (2). This diborane reacts with [Me3SiF2][S(NMe2)3)] to afford the anionic complex
      [2-mu2-F]-, which has been isolated as a [S(NMe2)3]+ salt. The cyclic
      voltammograms of diborane 2 as well as 1-(dimesitylboryl)-8-(10'-bora-9'
      thiaanthryl)naphthalene (1) exhibit two reversible reductions at E(1/2) = -2.200
      and -2.566 V (vs FcH/FcH+) for 1 and E(1/2) = -2.248 and -2.620 V (vs FcH/FcH+)
      for 2 corresponding to the sequential reduction of the two boron centers. These
      two waves simultaneously disappear upon fluoride addition, thus indicating the
      formation of fluoride chelate complexes [1-mu2-F]- and [2-mu2-F]-. To identify
      the origin of the high fluoride affinity displayed by these diboranes, the
      structures of 2 and [2-mu2-F]- have been studied experimentally and
      computationally. The crystallographic studies show that the structure of 2 is
      distorted, thus indicating the presence of important steric repulsions between
      the neighboring boryl moieties. By contrast, the structure of the anionic complex
      [2-mu2-F]- is much more sterically relaxed than that of 2, as indicated by a
      reduction of the B-B distance from 3.279(4) A in 2 to 2.922(7) A in [2-mu2-F]-.
      The structural results suggest that the high fluoride affinity displayed by 2
      results, at least in part, from the relief of steric repulsions induced by
      fluoride binding. Finally, the nature of the bonding as well as the strength of
      the interactions involved in the B-F-B bridge of [2-mu2-F]- has been studied
      using density functional theory calculations and Atoms-In-Molecules analyses.
      These calculations indicate that the enthalpic gain associated with the formation
      of two B-F bonds in [2-mu2-F]- only amounts to a fraction of the energy of a
      terminal B-F bond. These calculations also suggest that the relief of steric
      repulsions induced by fluoride binding in 2 may contribute to the high fluoride
      affinity of these types of molecules.

PMID- 16999412
TI  - Combined effects of diamines and carboxylate bridges on structural and magnetic
      properties of a series of polynuclear copper(II) complexes with 1,1
      cyclobutanedicarboxylic acid.
AB  - Six new copper(II) complexes of formula [Cu(mu-cbdca)(H2O)]n (1) (cbdca =
      cyclobutanedicarboxylate), [Cu2(mu-cbdca)2(mu-bipy)2]n (2) (bipy = 4,4'
      bipyridine), [Cu(mu-cbdca)(mu-bpe)]n (3) (bpe = 1,2-bis(4-pyridyl)ethane), [Cu(mu
      cbdca)(bpy)]2 (4) (bpy = 2,2'-bipyridine), [Cu(terpy)(ClO4)]2(mu-cbdca).H2O (5)
      (terpy = 2,2':6',2' '-terpyridine), and [Cu(cbdca)(phen) (H2O)].2H2O (6) (phen =
      1,10-phenanthroline) were obtained and structurally characterized by X-ray
      crystallography. Complex 1 is a two-dimensional network with a carboxylate
      bridging ligand in syn-anti (equatorial-equatorial) coordination mode. Complexes
      2 and 3 are formed by chains through syn-anti (equatorial-apical) carboxylate
      bridges, linked to one another by the corresponding amine giving two-dimensional
      nets. Complexes 4 and 5 are dinuclear, with the copper ions linked by two oxo
      (from two different carboxylate) bridging ligands in 4 and with only one
      carboxylate showing the unusual bis-unidentate mode in complex 5. Complex 6 is
      mononuclear, with the carboxylate linked to copper(II) in a chelated form.
      Intermolecular hydrogen bonds and pi-pi stacking interactions build an extended
      two-dimensional network. Magnetic susceptibility measurements of complexes 1-5 in
      the temperature range 2-300 K show the occurrence of weak ferromagnetic coupling
      for 1 and 4 (J = 4.76 and 4.44 cm(-1), respectively) and very weak
      antiferromagnetic coupling for 2, 3, and 5 (J = -0.94, -0.67, and -1.61 cm(-1),
      respectively). Structural features and magnetic values are compared with those
      reported for the similar copper(II) malonate and phenylmalonate complexes.

PMID- 16999413
TI  - Preparation and characterization of a family of Ru2 compounds bearing
      iodo/ethynyl substituents on the periphery.
AB  - A high-yield synthesis of mixed-bridging-ligand Ru2 compounds, Ru2(D(3,5
      Cl2Ph)F)(4-n)(OAc)nCl [n = 1 (1) and 2 (2)] was developed, where D(3,5-Cl2Ph)F is
      bis(3,5-dichlorophenyl)formamidinate. The acetate ligands in 1 and 2 can be
      quantitatively displaced with DMBA-I to yield Ru2(D(3,5-Cl2Ph)F)3(DMBA-I)Cl (3)
      and Ru2(D(3,5-Cl2Ph)F)2(DMBA-I)2Cl (4), respectively, where DMBA-I is N,N'
      dimethyl-4-iodobenzamidinate. When compound 2 was treated with 1 equiv of HDMBA
      I, a unique Ru2 compound containing three different types of bidentate bridging
      ligands, cis-Ru2(D(3,5-Cl2Ph)F)2(DMBA-I)(OAc)Cl (5), was obtained. Subsequent
      reactions between 3/4 and (trimethylsilyl)acetylene under Sonogashira coupling
      conditions resulted in Ru2(D(3,5-Cl2Ph)F)(4-n)(DMBA-C[triple bond]CSiMe3)nCl [n =
      1 (6) and 2 (8)] in excellent yields, which were converted to the corresponding
      bis(phenylacetylide) compounds Ru2(D(3,5-Cl2Ph)F)(4-n)(DMBA-C[triple
      bond]CSiMe3)n(C[triple bond]CPh)2 [n = 1 (7) and 2 (9)]. Structural studies of
      several compounds provided insights about the change in Ru2 coordination geometry
      upon the displacement of bridging and axial ligands. Voltammetric studies of
      these compounds revealed rich redox characteristics in all Ru2 compounds reported
      and a minimal electronic perturbation upon the peripheral Sonogashira
      modification.

PMID- 16999415
TI  - Mg(5.23)Sm(0.77)Sb4: an ordered superstructure derived from the Mg3Sb2 structure
      type.
AB  - The ternary polar intermetallic phase Mg(5.231(8))Sm(0.769(8))Sb4 has been
      obtained from solid-state reactions at 700-850 degrees C in sealed Ta or Nb
      containers when the synthetic conditions took into account its characteristic
      incongruent melting point. The compound crystallizes in the trigonal space group
      P3 (Z = 1) with a = 4.618(1) A and c = 14.902(6) A in a structure that derives
      from that of Mg3Sb2 (anti-La2O3 type). This composition appears to be near the
      lower limit of Sm content, and solutions with appreciably higher Sm contents are
      also stable [Mg(6-x)SmxSb4, x <or= 1]. The result provides the first example of a
      superstructure of a Mg3Sb2-like structure with a doubled c axis induced by
      ordering a mixture of the larger divalent Sm and Mg ions separately within
      alternate layers of octahedral sites. Still larger proportions of Sm also give
      rise to a second solid solution region in the parent Mg3Sb2 type structure
      (P3m1), Mg(3-y)SmySb4, 0 <or= y <or= 1. Retention of the same 3e- valence
      electron counts per antimony in all of these phases suggests that the compounds
      remain electron precise and Zintl phases. Analogous compounds with Ca, Sr, or Ba
      substitution have evidently not been investigated.

PMID- 16999414
TI  - Luminescent phosphine gold(I) thiolates: correlation between crystal structure
      and photoluminescent properties in [R3PAu{SC(OMe)=NC6H4NO2-4}] (R = Et, Cy, Ph)
      and [(Ph2P-R-PPh2){AuSC(OMe)=NC6H4NO2-4}2] (R = CH2, (CH2)2, (CH2)3, (CH2)4, Fc).
AB  - X-ray crystallography shows the gold atoms in [R3PAu{SC(OMe)=NC6H4NO2-4}] (R =
      Et, Cy, Ph; 1-3, respectively) and [(Ph2P-R-PPh2){AuSC(OMe)=NC6H4NO2-4}(2)] (R =
      CH2, (CH2)2, (CH2)3, (CH2)4, Fc; 4-8, respectively) are linearly coordinated by
      phosphorus and thiolate-sulfur; weak intramolecular Au...O interactions are
      featured in all structures. The smaller ethyl substituents in 1 allow for
      supramolecular association via Au...S and Au...Au interactions that are not found
      in 2 and 3, which contain larger phosphorus-bound Cy and Ph groups, respectively.
      Intramolecular Au...Au interactions are found in the dppm, dppe, dppp, and Fc
      structures but not in the dppp analogue, for which an anti conformation was
      found. The structures have been correlated with the results from photophysical
      study conducted in the solid state. Thus, photoexcitation of 1-7 with lambda >
      350 in the solid state and in solution produces green and blue luminescence,
      respectively. The spectra in each medium are remarkably similar to each other,
      and so the emission energy and excitation maxima observed for 1-7 appear to be
      independent of the nature of the ancillary phosphines, as well as the presence or
      absence of Au...Au interactions, either intermolecularly or intramolecularly.

PMID- 16999416
TI  - Mono- and polynuclear complexes of the model nucleobase 1-methylcytosine.
      Synthesis and characterization of cis-[(PMe2Ph)2Pt{(1-MeCy(-H)}]3(NO3)3 and cis
      [(PPh3)2Pt{1-MeCy(-H)}(1-MeCy)]NO3.
AB  - The hydroxo complex cis-[L2Pt(mu-OH)]2(NO3)2 (L = PMe2Ph), in various solvents,
      reacts with 1-methylcytosine (1-MeCy) to give as the final product the cyclic
      species cis-[L2Pt{1-MeCy(-H),N 3N 4}]3(NO3)3 (1) in high or quantitative yield. X
      ray analysis of 1 evidences a trinuclear species with the NH(2)-deprotonated
      nucleobases bridging symmetrically the metal centers through the N3 and N4
      donors. A multinuclear NMR study of the reaction in DMSO-d6 reveals the initial
      formation of the dinuclear species cis-[L2Pt{1-MeCy(-H),N 3N 4}]2(2+) (2), which
      quantitatively converts into 1 following a first-order kinetic law (at 50 degrees
      C, t(1/2) = 5 h). In chlorinated solvents, the deprotonation of the nucleobase
      affords as the major product (60-70%) the linkage isomer of 1, cis-[L2Pt{1-MeCy(
      H)}]3(3+) (3), in which three cytosinate ligands bridge unsymmetrically three cis
      L2Pt(2+) units. In solution, 3 slowly converts quantitatively into the
      thermodynamically more stable isomer 1. No polynuclear adducts were obtained with
      the hydroxo complex stabilized by PPh3. cis-[(PPh3)2Pt(mu-OH)]2(NO3)2 reacts with
      1-MeCy, in DMSO or CH2Cl2, to give the mononuclear species cis-[(PPh3)2Pt{1-MeCy(
      H)}(1-MeCy)](NO3) (4) containing one neutral and one NH2-deprotonated 1-MeCy
      molecule, coordinated to the same metal center at the N3 and N4 sites,
      respectively. X-ray analysis and NMR studies show an intramolecular H bond
      between the N4 amino group and the uncoordinated N3 atom of the two nucleobases.

PMID- 16999417
TI  - Syntheses and structural properties of rare earth carbodiimides.
AB  - Crystalline samples of rare earth carbodiimides were synthesized by solid-state
      metathesis reactions of rare earth trichlorides with lithium cyanamide in sealed
      silica ampules. Two distinct structures were determined by single-crystal X-ray
      diffraction. The structure determined for Sm2(CN2)3 [C2/m, Z = 2, a = 14.534(2)
      A, b = 3.8880(8) A, c = 5.2691(9) A, beta = 95.96(2) degrees , R1 = 0.0267, and
      wR2 = 0.0667] was assigned for RE2(CN2)3 compounds with RE = Y, Pr, Nd, Sm, Gd,
      Tb, Dy, Ho, and Er, and the structure determined for Lu2(CN2)3 [R32, Z = 3, a =
      6.2732(8) A, c = 14.681(2) A, R1 = 0.0208, and wR2 = 0.0526] was assigned for the
      smallest rare earth ions with RE = Tm, Yb, and Lu by powder X-ray diffraction.
      Both types of crystal structures are characterized by layers of [NCN](2-) ions
      whose arrangements can be derived from the motif of a closest packed layer of
      sticks. These layers alternate with layers of rare earth ions in a one-by-one
      sequence. Different tilting arrangements of the N-C-N-axes relative to the
      stacking directions (c) and different arrangements of RE3+ ions within metal atom
      layers account for the two distinct structures in which Sm3+ and Lu3+ ions adopt
      the coordination numbers 7 and 6, respectively.

PMID- 16999418
TI  - [CpNi(dithiolene)] (and diselenolene) neutral radical complexes.
AB  - Various preparations of the neutral radical [CpNi(dddt)] complex (dddt = 5,6
      dihydro-1,4-dithiin-2,3-dithiolate) were investigated with CpNi sources, [Cp2Ni],
      [Cp2Ni](BF4), [CpNi(CO)]2, and [CpNi(cod)](BF4), and dithiolene transfer sources,
      O=C(dddt), the naked dithiolate (dddt(2-)), the monoanion of square-planar Ni
      dithiolene complex (NBu4)[Ni(dddt)2], and the neutral complex [Ni(dddt)2]. The
      reaction of [CpNi(cod)](BF4) with (NBu4)[Ni(dddt)2] gave the highest yield for
      the preparation of [CpNi(dddt)] (86%). [CpNi(ddds)] (ddds = 5,6-dihydro-1,4
      dithiin-2,3-diselenolate), [CpNi(dsdt)] (dsdt = 5,6-dihydro-1,4-diselenin-2,3
      dithiolate), [CpNi(bdt)] (bdt = 1,2-benzenedithiolate), and [CpNi(bds)] (bds =
      1,2-benzenediselenolate) were synthesized by the reactions of [Cp2Ni] with the
      corresponding neutral Ni dithiolene complexes [Ni(ddds)2]2, [Ni(dsdt)2],
      [Ni(bdt)2], and [Ni(bds)2], respectively. The five, formally Ni(III), radical
      complexes oxidize and reduce reversibly. They exhibit, in the neutral state, a
      strong absorption in the NIR region, from 1000 nm in the dddt/ddds/dsdt series to
      720 nm in the bdt/bds series with epsilon values between 2500 and 5000 M(-1) cm(
      1). The molecular and solid state structures of the five complexes were
      determined by X-ray structure analyses. [CpNi(dddt)] and [CpNi(ddds)] are
      isostructural, while [CpNi(dsdt)] exhibits a closely related structure.
      Similarly, [CpNi(bdt)] and [CpNi(bds)] are also isostructural. Correlations
      between structural data and magnetic measurements show the presence of alternated
      spin chains in [CpNi(dddt)], [CpNi(ddds)], and [CpNi(dsdt)], while a remarkably
      strong antiferromagnetic interaction in [CpNi(bdt)] and [CpNi(bds)] is attributed
      to a Cp...Cp face-to-face sigma overlap, an original feature in organometallic
      radical complexes.

PMID- 16999419
TI  - BF2 complex of fluorinated dipyrrolyldiketone: a new class of efficient receptor
      for acetate anions.
AB  - The beta-fluorinated derivative (2b) of the 1,3-dipyrrolyl-1,3-propanedione BF2
      complex has been prepared from 3,4-difluoropyrrole and malonyl chloride, followed
      by treatment with BF3.OEt2. Despite the simple, acyclic, and neutral structure,
      2b exhibits efficient 1:1 binding for anions in CH2Cl2 using the bridging CH and
      pyrrole NH as interaction sites. The binding constant (Ka) of 2b for acetate
      (CH3CO(2-)), associating more effectively than anions such as F-, Cl-, Br-,
      H2PO(4-), and HSO(4-), is estimated to be 9.6 x 10(5) M(-1), approximately 9
      times larger than that of the beta-H derivative 2a (1.1 x 10(5) M(-1)). The UV
      vis and fluorescence spectral changes of 2b elucidate the effective recognition
      of an amino acid, such as phenylalanine, in the anionic form; this is also
      supported by CD spectral changes with mirror images by L- and D-isomers.
      Furthermore, in the solid state, BF2 complex 2b provides Cl- -bridged
      supramolecular networks and, in sharp contrast, deprotonated "anionic" self
      assembled structures by F- binding.

PMID- 16999420
TI  - Oblate deltahedra in dimetallaboranes: geometry and chemical bonding.
AB  - A new series of nonspherical and very oblate deltahedra, conveniently called the
      oblatocloso deltahedra, is found in dimetallaboranes among which the
      dirhenaboranes Cp2Re2B(n-2)H(n-2) (8 <or= n <or= 12) are the prototypes. The
      D(6h) hexagonal bipyramid is the first member of this series (n = 8). However,
      the higher members of the series are not bipyramids but are derivable from them
      by a number of diamond-square-diamond processes. A viable model for the skeletal
      bonding in the oblatocloso dimetallaboranes can be developed if the two metal
      vertices, typically degree 6 or 7 vertices, are assumed each to contribute five
      internal orbitals rather than the three internal orbitals assumed by the Wade
      Mingos rules. This leads to 2n + 4 actual skeletal electrons for an n vertex
      oblatocloso dimetallaborane rather than the Wadean 2n - 4 skeletal electrons. The
      surface bonding of an n vertex oblatocloso dimetallaborane then consists of n
      three-center two-electron bonds similar to that in corresponding isocloso
      metallaboranes thereby leaving four orbitals and four electrons for a metal-metal
      double bond inside the deltahedron. Removal of one or two boron vertices from
      oblatocloso deltahedra leads to oblatonido and oblatoarachno dimetallaboranes,
      respectively, having the same number of skeletal electrons as the oblatocloso
      deltahedra from which they are derived.

PMID- 16999421
TI  - Theoretical designs for neutral five-membered carbene analogues of the group 13
      elements: a new target for synthesis.
AB  - Potential energy surfaces for the chemical reactions of neutral five-membered
      group 13 carbenoids have been studied using density functional theory
      (B3LYP/LANL2DZ). Five five-membered group 13 carbenoid species, HCMeP(PhN)2X,
      where X = B, Al, Ga, In, and Tl, have been chosen as model reactants in this
      work. Also, three kinds of chemical reaction, C-H bond insertion, alkene
      cycloaddition, and dimerization, have been used to study the chemical
      reactivities of these group 13 carbenoids. Our present theoretical work predicts
      that the larger the angleNXN bond angle in the neutral five-membered group 13
      carbenoid, the smaller the singlet-triplet splitting, the lower the activation
      barrier, and, in turn, the more rapid are its various chemical reactions.
      Moreover, the theoretical investigations suggest that the relative carbenoidic
      reactivity decreases in the order B > Al > Ga > In > Tl. That is, the heavier the
      group 13 atom (X), the more stable is its carbenoid with respect to chemical
      reactions. As a result, we predict that the neutral five-membered group 13
      carbenoids (X = Al, Ga, In, and Tl) should be stable, readily synthesized, and
      isolated at room temperature. Furthermore, the neutral five-membered group 13
      carbenoid singlet-triplet energy splitting, as described in the configuration
      mixing model attributed to the work of Pross and Shaik, can be used as a
      diagnostic tool to predict their reactivities. The results obtained allow a
      number of predictions to be made.

PMID- 16999422
TI  - Diverse structures and dimensionalities in hybrid frameworks of strontium and
      lanthanum with isomeric dihydroxybenzoates.
AB  - Investigations of Sr and La derivatives of 2,3-, 2,4-, 3,5-, and 2,6
      dihydroxybenzoic acids have revealed that it is possible to obtain chain and
      layered structures of these materials. [Sr2(2,3-DHB)4(H2O)4].3H2O, I, and [Sr(2,4
      DHB)2(H2O)4].H2O, II, are both one-dimensional coordination polymers based on
      dimers; both the carboxylate and phenolic oxygens bond to the metal in I and only
      the carboxylate oxygens bond to the metal in II. [Sr(3,5-DHB)2(H2O)2].4H2O, III,
      has a one-dimensional chain structure with large channels and involves extended
      Sr-O-Sr connectivity. [Sr(CH3CO2)(2,4-DHB)(H2O)3].H2O, IV, also has a chain
      structure with extended Sr-O-Sr connectivity, but the chain structure is formed
      by bridging acetate units, unlike in III where the Dihydroxybenzoate (DHB) is the
      bridging unit. [Sr(2,6-DHB)2(H2O)2].0.5H2O, V, is a two-dimensional coordination
      polymer where both carboxylate and phenolic oxygens coordinate to the metal. A
      lanthanum compound with the composition [La(CH3CO2)2(2,4-DHB)H2O].0.18H2O, VI,
      with a one-dimensional chain structure with extended La-O-La connectivity, has
      been prepared. Besides these chain and layered structures, zero-dimensional
      dimers of rare-earth DHBs with the general formula [La(CH3CO2)2(DHB)(H2O)2], with
      3,5- (VII), 2,6- (VIII), and 2,3-dihydroxybenzoic acids (IX) have been
      synthesized. The diverse structures of the strontium and lanthanum DHBs are
      described. The study demonstrates that it is possible to obtain interesting
      structures of metal DHBs with different dimensionalities. The structures appear
      to be controlled largely by geometrical rather than electronic factors.

PMID- 16999423
TI  - Synthesis, crystal structure, and magnetic studies of one-dimensional cyano
      bridged Ln3+-Cr3+ complexes with bpy as a blocking ligand.
AB  - The reaction of Ln(NO3)3.aq with K3[Cr(CN)6] and 2,2'-bipyridine (bpy) in a
      water/ethanol solution led to two families of complexes: 4 one-dimensional (1D)
      complexes of the formula trans-[Cr(CN)4(mu-CN)2Ln(H2O)3(bpy)2]n.4nH2O.3.5nbpy
      (Ln3+ = La, Ce, Pr, and Nd) and 10 1D complexes of the formula trans-[Cr(CN)4(mu
      CN)2Ln(H2O)4(bpy)]n.3.5nH2O.1.5nbpy (Ln3+ = Nd, Sm, Eu, Tb, Dy, Ho, Er, Tm, Yb,
      and Lu). The structures for the fourteen complexes [LaCr]n (1), [CeCr]n (2),
      [PrCr]n (3), [NdCr]n (4), [NdCr]n (4'), [SmCr]n (5), [EuCr]n (6), [TbCr]n (7),
      [DyCr]n (8), [HoCr]n (9), [ErCr]n (10), [TmCr]n (11), [YbCr]n (12), and [LuCr]n
      (13) have been solved. Complexes 1-4 crystallize in the orthorhombic space group
      Pbam and are isomorphous; complexes 4'-13 crystallize in the triclinic space
      group PI and are isomorphous. The X-ray structural characterization of complexes
      1-4 shows the presence of a discrete decameric water cluster built around a
      cyclic hexameric core stabilized by the solid-state structure, which represents
      another new mode of association of water molecules. The Ln3+-Cr3+ magnetic
      interaction is negligible in 6 and 12, antiferromagnetic in 2, 4', 7, 8, 9, 10,
      and 11, and unresolved for 3. The complex 5 is a ferrimagnet because its magnetic
      studies suggest the onset of a very weak ferromagnetic three-dimensional
      ordering.

PMID- 16999424
TI  - Structural polarity induced by cooperative hydrogen bonding and lone-pair
      alignment in the molecular uranyl iodate Na2[UO2(IO3)4(H2O)].
AB  - Na2[UO2(IO3)4(H2O)] has been synthesized under mild hydrothermal conditions. Its
      structure consists of Na+ cations and [UO2(IO3)4(H2O)](2-) anions. The
      [UO2(IO3)4(H2O)](2-) anions are formed from the coordination of a nearly linear
      uranyl, UO2(2+), cation by four monodentate IO(3-) anions and a coordinating
      water molecule to yield a pentagonal bipyramidal environment around the uranium
      center. The water molecules form intermolecular hydrogen bonds with the terminal
      oxo atoms of neighboring [UO2(IO3)4(H2O)](2-) anions to yield one-dimensional
      chains that extend down the b axis. There are two crystallographically unique
      iodate anions in the structure of Na2[UO2(IO3)4(H2O)]. One of these anions is
      aligned so that the lone-pair of electrons is also directed along the b axis. The
      overall structure is therefore polar, owing to the cooperative alignment of both
      the hydrogen bonds and the lone-pair of electrons on iodate. The polarity of the
      monoclinic space group C2 (a = 11.3810(12) A, b = 8.0547(8) A, c = 7.6515(8) A,
      beta = 90.102(2) degrees , Z = 2, T = 193 K) found for this compound is
      consistent with the structure. Second-harmonic generation of 532 nm light from a
      1064 nm laser source yields a response of approximately 16x alpha-SiO2.

PMID- 16999425
TI  - Syntheses and structures of [M{In(SC{O}Ph)4}2] (M = Mg and Ca): single molecular
      precursors to MIn2S4 materials.
AB  - The compounds [Mg{In(SC{O}Ph)4}2] (1) and [Ca(H2O)x{In(SC{O}Ph)4}2].yH2O (x = 0,
      y = 1, 2 major product; x = 1, y = 0, 2a minor product; x = 2, y = 2, 2b minor
      product) have been synthesized by reacting InCl3 and M(SC{O}Ph)2 (M = Mg and Ca)
      prepared in situ in the molar ratio 1:2. The structures of 1, 2a, and 2b have
      been determined by X-ray crystallography. The structure of 1 consists of two
      tetrahedral [In(SC{O}Ph)4]- anions sandwiching the Mg(II) metal ions through six
      carbonyl O atoms. The coordination geometry at the Mg(II) metal atom is distorted
      octahedral with an O(6) donor set. The structures of 2a and 2b consist of two
      [In(SC{O}Ph)4]- anions sandwiching the Ca(II) metal ion through five and four
      carbonyl O atoms, and the octahedral coordination at the Ca(II) centers is
      completed by one and two aqua ligands, respectively. Two aqua ligands and two
      lattice water molecules form a H-bonded water chain in the channel created by
      [Ca{In(SC{O}Ph)4}2] molecules in the crystal structure of 2b. The thermal
      decomposition of 1 and 2 indicated the formation of the corresponding MIn2S4
      materials, and this was confirmed by X-ray powder diffraction patterns.

PMID- 16999426
TI  - Syntheses, structures, physical properties, and theoretical studies of CeMxOS (M
      = Cu, Ag; x approximately 0.8) and CeAgOS.
AB  - Black single crystals of the two nonstoichiometric cerium coinage-metal
      oxysulfide compounds CeCu(x)OS and CeAg(x)OS (x approximately 0.8) have been
      prepared by the reactions of Ce2S3 and CuO or Ag2O at 1223 or 1173 K,
      respectively. A black powder sample of CeAgOS has been prepared by the
      stoichiometric reaction of Ce2S3, CeO2, Ag2S, and Ag at 1073 K. These
      isostructural materials crystallize in the ZrSiCuAs structure type with two
      formula units in the tetragonal space group P4/nmm. Refined crystal structure
      results and chemical analyses provide evidence that the previously known
      anomalously small unit-cell volume of LnCuOS for Ln = Ce (Ln = rare-earth metal)
      is the result of Cu vacancies and the concomitant presence of both Ce3+ and Ce4+.
      Both CeCu(0.8)OS and CeAgOS are paramagnetic with mu(eff) values of 2.13(6) and
      2.10(1) mu(B), respectively. CeCu(0.8)OS is a p-type semiconductor with a thermal
      activation energy Ea = 0.22 eV, sigma(electrical) = 9.8(1) 10(-3) S/cm at 298 K,
      and an optical band gap Eg < 0.73 eV. CeAgOS has conductivity sigma(conductivity)
      = 0.16(4) S/cm and an optical band gap Eg = 0.71 eV at 298 K. Theoretical
      calculations with an on-site Coulomb repulsion parameter indicate that the Ce 4f
      states are fully spin-polarized and are not localized in CeCuOS, CeCu(0.75)OS, or
      CeAgOS. Calculated band gaps for CeCu(0.75)OS and CeAgOS are 0.6 and 0.8 eV,
      respectively.

PMID- 16999427
TI  - Electronic transitions in [Re6S8X6](4-) (X = Cl, Br, I): results from time
      dependent density functional theory and solid-state calculations.
AB  - Relativistic time-dependent density functional theory (TDDFT) calculations were
      performed on the excited states of the [Re6S8X6](4-) (X = Cl, Br, I) series. For
      all members of the series, the lowest excited states in the spectra do not
      correspond to a ligand-to-metal (or ligand-to-cluster) excitation but rather a
      cluster-cluster transition from the HOMO e(g) to antibonding t(1u) orbitals with
      only a modest admixture of Re-X sigma* character. These results lead to a re
      evaluation of the role of the axial ligand in these compounds. The calculated
      excitation energies reproduce the experimental absorption and emission spectra.
      This work also confirms previous TDDFT calculations on the emission energies.
      Results for discrete cluster ions are compared with those obtained from
      calculations in the solid state in Cs4[Re6S8X6].CsX (X = Cl, Br) and
      Cs4[Re6S8I6].2CsI. Significant differences are seen in the relatively higher
      energies of the antibonding t(1u) orbital in the solid-state case, and an
      inversion in the orbital character of the two allowed absorptions is calculated.
      The e(g) (HOMO)-to-a(2g) (LUMO) orbital energy differences corresponding to the
      emission transition are quite comparable for the solid state and discrete cluster
      calculations, and both overestimate the observed emission energy by the same
      margin.

PMID- 16999428
TI  - Bimetallic clusters of iron with palladium and platinum. Synthesis and structures
      of Fe2(CO)9[M(PBu(t)3)]2 (M = Pd or Pt) and Fe2(CO)8[Pt(PBu(t)3)]2(mu-H)2.
AB  - The reaction of Fe2(CO)9 with Pd(PBu(t)3)2 and Pt(PBu(t)3)2 yielded the Fe-Pd and
      Fe-Pt cluster complexes Fe2(CO)9[M(PBu(t)3)]2, M = Pd (8) or Pt (9). The
      structures of 8 and 9 are analogous and consist of nearly planar butterfly
      clusters of two palladium/platinum atoms in the wing-tip positions and two
      mutually bonded iron atoms, Fe-Fe = 2.9582(11) A in 8 and 2.9100 (9) A in 9.
      Compound 8 decomposes to form the mononuclear iron compound Fe(CO)4(PBu(t)3) (11)
      when heated at 68 degrees C. The reaction of Pt(PBu(t)3)2 with Fe2(CO)9 in the
      presence of hydrogen at 127 degrees C yielded the dihydrido complex
      Fe2(CO)8[Pt(PBu(t)3)]2(mu-H)2 (10). Compound 10 contains a closed Fe2Pt2
      tetrahedral cluster with hydrido ligands bridging two of the Fe-Pt bonds.
      Compounds 8, 9, and 10 were structurally characterized crystallographically.

PMID- 16999429
TI  - Chromogenic indicator for anion reporting based on an N-substituted
      oxoporphyrinogen.
AB  - 5,10,15,20-Tetrakis-3,5-di-tert-butyl-4-oxocyclohexadienylidene porphyrinogen and
      its di-N-benzylated derivative are solvatochromic dyes capable of binding anionic
      species. The influence of solvent polarity and hydrogen bonding on their
      electronic absorption spectra was observed. Hydrogen bonding by the porphyrinogen
      amine protons of acetone solvent molecules could be observed in the solid state.
      The acetone solvate of N21N23-dibenzyl-5,10,15,20-tetrakis-3,5-di-tert-butyl-4
      oxocyclohexadienylidene porphyrinogen crystallized under anhydrous conditions in
      the space group P with cell dimensions a = 12.1693(11) A, b = 17.5849(13) A, c =
      21.0965(17) A, alpha = 69.870(4) degrees , beta = 78.140(4) degrees , gamma =
      82.865(5) degrees . These porphyrinogens are capable of binding a variety of
      anions and can be used to distinguish fluoride chromogenically from the other
      halide anions. Solvatochromism was combined with anion binding in an attempt to
      provide more selective tests for anions. The anion binding properties were
      investigated using UV/vis spectrophotometry and 1H NMR spectroscopy.

PMID- 16999430
TI  - Influence of Hartree-Fock exchange on the calculated Mossbauer isomer shifts and
      quadrupole splittings in ferrocene derivatives using density functional theory.
AB  - Influence of molecular geometry, type of exchange-correlation functional, and
      contraction scheme of basis set applied at the iron nuclei have been tested in
      the calculation of 57Fe Mossbauer isomer shifts and quadrupole splittings for a
      wide range of ligand types, as well as oxidation and spin states, in inorganic
      and organometallic systems. It has been found that uncontraction of the s-part of
      Wachter's full-electron basis set at the iron nuclei does not appreciably improve
      the calculated isomer shifts. The observed correlations for all tested sets of
      geometries are close to each other and predominantly depend on the employed
      exchange-correlation functional with B3LYP functional being slightly better as
      compared to BPW91. Both hybrid (B3LYP) and pure (BPW91) exchange-correlation
      functionals are suitable for the calculation of isomer shifts in organometallic
      compounds. Surprisingly, it has been found that the hybrid B3LYP exchange
      correlation functional completely fails in accurate prediction of quadrupole
      splittings in ferrocenes, while performance of the pure BPW91 functional for the
      same systems was excellent. This observation has been explained on the basis of
      relationship between the amount of Hartree-Fock exchange involved in the applied
      exchange-correlation functional and the calculated HOMO-LUMO energy gap in
      ferrocenes. On the basis of this explanation, use of only pure exchange
      correlation functionals has been suggested for accurate prediction of Mossbauer
      spectra parameters in ferrocenes.

PMID- 16999431
TI  - Mono- and dinuclear oxovanadium(V)calixarene complexes and their activity as
      oxidation catalysts.
AB  - The background of the investigation is constituted by reactive moieties and
      intermediates playing relevant roles on the surfaces of vanadiumoxide-based
      catalysts during the oxygenation/dehydrogenation of organic substrates. With the
      aim of modeling such species, a series of mono- and dinuclear charged and
      uncharged vanadium oxo complexes containing p-tert-butylated calix[4]arene and
      calix[8]arene ligands (denoted H4B and H8B' ', respectively, in the protonated
      forms) has been synthesized and characterized: PPh4[O=VB] ((PPh41), O=VB(OAc)
      (2), PPh4[O2V2HB' '] (3), and [mu-O(O=V(OMe))2B(Me2)] (4), where superscripts OAc
      and Me2 indicate that one or two protons of H4B are substituted by these
      residues, respectively. These compounds were analyzed both in solution and by
      means of single-crystal X-ray crystallography; it turned out that the crystal
      structures are retained on dissolution (2 changed only from the paco to the cone
      structure). In the case of 4, it could be shown that the bulk product consists of
      a mixture of two isomers (4t and 4c) differing in the relative positions of the
      vanadium-bound methoxy groups. Subsequently, all compounds were tested as
      catalysts for the oxidation of alcohols with O2. It turned out that the two
      dinuclear complexes efficiently catalyze the oxidation of 1-phenyl-1-propargyl
      alcohol and fluorenol; in addition, they even show some activity with respect to
      the oxidation of dihydroanthracene. This may hint to a higher activity of
      dinuclear sites on the surfaces of heterogeneous catalysts as well.

PMID- 16999432
TI  - Structural diversity within analogous compounds: syntheses and studies of
      M(SCH2CH2NH2)Cl (M = Zn, Cd, Hg).
AB  - The novel complexes [Zn(L)Cl] (1), [Cd(L)Cl] (2), [Hg(L)Cl] (3),
      {[Hg(L)Cl].NaOH.2H2O} (3.NaOH.2H2O), and {[Hg3(HL)2Cl6].2H2O} (4) (L = 
      SCH2CH2NH2) were prepared and investigated by means of IR spectroscopy and single
      crystal X-ray diffraction. The crystal structures of 1, 2, and 3.NaOH.2H2O show
      chelating N,S-coordination of the cysteaminate ligand, bridging S, and terminally
      coordinating Cl. Apart from these common features, the coordination geometries
      and modes of intermolecular association are different. 1 forms a cyclic tetramer
      with a Zn4S4 ring, and 3.NaOH.2H2O contains one-dimensional [Hg(L)Cl]n chains
      with S-bridged Hg atoms. Zn and Hg atoms in 1 and 3.NaOH.2H2O are tetracoordinate
      with a distorted tetrahedral M(ClNS2) geometry (M = Zn, Hg). Each Cd atom of 2
      binds to three S atoms and vice versa, such that layers of distorted Cd3S3
      hexagons are formed. 2 is the first example for a compound exhibiting a group 12
      group 16 layer structure, which can be described as an analogue of a graphite
      layer. Additionally, each Cd atom binds to a chlorine atom and a nitrogen atom
      from a cysteaminate ligand resulting in pentacoordination with a distorted
      trigonal bipyramidal Cd(ClNS3) geometry. 4 contains two differently coordinate Hg
      atoms. One displays a distorted trans-octahedral Hg(Cl4S2) geometry, while the
      other is coordinated by four Cl atoms and one S atom and additionally forms a
      long Hg...Cl contact.

PMID- 16999433
TI  - Synthesis, photophysical, photochemical, and redox properties of nitrospiropyrans
      substituted with Ru or Os tris(bipyridine) complexes.
AB  - Photochromic nitrospiropyrans substituted with 2,2'-bipyridine (bpy),
      [Ru(bpy)3]2+, and [Os(bpy)3]2+ groups were synthesized, and their photophysical,
      photochemical, and redox properties investigated. Substitution of the spiropyran
      with the metal complex moiety results in strongly decreased efficiency of the
      ring-opening process as a result of energy transfer from the excited spiropyran
      to the metal center. The lowest excited triplet state of the spiropyran in its
      open merocyanine form is lower in energy than the excited triplet MLCT level of
      the [Ru(bpy)3]2+ moiety but higher in energy than for [Os(bpy)3]2+, resulting in
      energy transfer from the excited ruthenium center to the spiropyran but inversely
      in the osmium case. The open merocyanine form reduces and oxidizes
      electrochemically more easily than the closed nitrospiropyran. Like
      photoexcitation, electrochemical activation also causes opening of the spiropyran
      ring by first reducing the closed form and subsequently reoxidizing the
      corresponding radical anion in two well-resolved anodic steps. Interestingly, the
      substitution of the spiropyran with a Ru or Os metal center does not affect the
      efficiency of this electrochemically induced ring-opening process, different from
      the photochemical path.

PMID- 16999434
TI  - Syntheses, characterization, and catalytic ability in alkane oxygenation of
      chloro(dimethyl sulfoxide)ruthenium(II) complexes with tris(2-pyridylmethyl)amine
      and its derivatives.
AB  - New ruthenium(II) complexes having a tetradentate ligand such as tris(2
      pyridylmethyl)amine (TPA), tris[2-(5-methoxycarbonyl)pyridylmethyl]amine [5
      (MeOCO)3-TPA], tris(2-quinolylmethyl)amine (TQA), or bis(2
      pyridylmethyl)glycinate (BPG) have been prepared. The reaction of the ligand with
      [RuCl2(Me2SO)4] resulted in a mixture of trans and cis isomers of the
      chloro(dimethyl sulfoxide-kappaS)ruthenium(II) complexes containing a TPA or a
      BPG, whereas a trans(Cl,N(amino)) isomer was selectively obtained for 5-(MeOCO)3
      TPA and TQA. The trans and cis isomers of the [RuCl(TPA)(Me2SO)]+ complex were
      easily separated by fractional recrystallization. The molecular structures of
      trans- and cis(Cl,N(amino))-[RuCl(TPA)(Me2SO)]+ complexes and the
      trans(Cl,N(amino))-[RuCl{5-(MeOCO)3-TPA}(Me2SO)]+ complex have been determined by
      X-ray structural analyses. The reaction of TPA with [RuCl2(PhCN)4] gave a single
      isomer of the chloro(benzonitrile)ruthenium(II) complex, whereas the
      bis(benzonitrile)ruthenium(II) complex was obtained with BPG. The
      cis(Cl,N(amino))-[RuCl(TPA)(Me2SO)]+ complex is thermodynamically much less
      stable than the trans isomer and isomerizes in dimethyl sulfoxide at 65-100
      degrees C. Oxygenation of alkanes catalyzed by these ruthenium(II) complexes has
      been examined. The chloro(dimethyl sulfoxide-kappaS)ruthenium(II) complexes with
      TPA and its derivatives using m-chloroperbenzoic acid as a cooxidant showed high
      catalytic ability. Adamantane was efficiently and selectively oxidized to give 1
      adamantanol up to 88%. The chloro(dimethyl sulfoxide-kappaS)ruthenium(II) complex
      with 5-(MeOCO)3-TPA was found to be the most active catalyst among the complexes
      examined.

PMID- 16999435
TI  - Substituent effects on Gd(III)-based MRI contrast agents: optimizing the
      stability and selectivity of the complex and the number of coordinated water
      molecules.
AB  - Hydroxypyridinone (HOPO)-based Gd(III) complexes have previously been shown to
      exhibit high relaxivity, especially at the high magnetic fields that are
      clinically relevant for present and future clinical use. This is due to more than
      one coordinated water molecule exchanging rapidly with bulk solvent. These
      complexes, however, present poor water solubility. Heteropodal complexes which
      include a terephthalamide (TAM) moiety maintain the high relaxivity
      characteristics of the HOPO family and have been functionalized with solubilizing
      substituents of various charges. The charge of the substituent significantly
      affects the stability of the Gd(III) complex, with the most stable complex
      presenting a neutral charge. The solubilizing substituent also moderately affects
      the affinity of the complex for physiological anions, with the highest affinity
      observed for the positively charged complex. In any case, only two anions,
      phosphate and oxalate, measureably bind the Gd(III) complex with weak affinities
      that are comparable to other q = 1 complexes and much weaker than DO3A, q = 2
      based complexes. Furthermore, unlike poly(amino-carboxylate)-based complexes,
      HOPO-based Gd(III) complexes do not show any noticeable interaction with
      carbonates. The nature of the substituent can also favorably stabilize the
      coordination of a third water molecule on the Gd(III) center and lead to a nine
      coordinate ground state. Such complexes that attain q = 3 incorporate a
      substituent beta to the terminal amide of the TAM podand that is a hydrogen-bond
      acceptor, suggesting that the third water molecule is coordinated to the metal
      center through a hydrogen-bond network. These substituents include alcohols,
      primary amines, and acids. Moreover, the coordination of a third water molecule
      has been achieved without destabilizing the complex.

PMID- 16999436
TI  - Dioxotungsten 1,2-benzenedithiolate complex stabilized by NH...S hydrogen bonds.
AB  - Novel dioxo-tungsten(VI) bis(1,2-benzenedithiolate) complexes with neighboring
      amide groups, as models for tungsten enzymes, (NEt4)2[W(VI)O2{1,2-S(2)-3,6
      (RCONH)2C6H2}2] (R = CH3, t-Bu), were designed and synthesized. The presence of
      the NH...S hydrogen bond was confirmed through IR spectrometry and X-ray
      crystallographic analysis. In the W(VI)O2 complexes, the NH...S hydrogen bond
      trans to the oxo ligand is stronger than that cis to oxo. On the basis of
      comparisons with [W(VI)O2(1,2-S2C6H4)2](2-), the NH...S hydrogen bond positively
      shifted the W(VI)/W(V) redox potentials and depressed the reduction by benzoin or
      triphenylphosphine. These results suggest that the NH...S hydrogen bond
      stabilizes the oxo ligand through trans influence and regulates O-atom transfer
      in tungsten and molybdenum enzymes.

PMID- 16999438
TI  - Nanocluster formation and stabilization fundamental studies: investigating
      "solvent-only" stabilization en route to discovering stabilization by the
      traditionally weakly coordinating anion BF4- plus high dielectric constant
      solvents.
AB  - The nanocluster literature contains a wide variety of nanocluster stabilizing
      agents. In addition to the plethora of putative stabilizing additives, 12 claims
      appear of "solvent-only" stabilization of transition-metal nanoclusters-a
      hypothesis that is tested for the first time as part of the present studies. When
      the two main modes of nanocluster stabilization, electrostatic and steric are
      considered, "solvent-only" stabilization can only be steric (i.e., is not
      electrostatic). Solvent-only stabilization would, therefore, require that a
      strongly coordinated, perhaps even kinetically nonlabile, solvent be present on
      the nanocluster surface. Hence, an investigation has been conducted into
      potential sources for the stabilization of prototype Ir(0)n transition-metal
      nanoclusters prepared from [(1,5-COD)Ir(CH3CN)2][BF4] in five different solvents,
      with a special focus on the formulation and testing of alternative hypotheses
      regarding the true source of the nanocluster stabilization in putative solvent
      only stabilization conditions. Seven total hypotheses are tested with five being
      initially ruled out; they are, namely, stabilization by (i) trace chloride (ii),
      surface hydrides, (iii) scavenged charge, (iv) solvent oxidative addition
      reactions with the nanocluster surface, or (v) polymerized solvent. This led in
      turn to two additional main alternative hypotheses: (vi) nanocluster surface
      ligation by high-donor number solvents (i.e., in the absence of anions) and (vii)
      nanocluster stabilization by surface-coordination of the traditionally weakly
      coordinating anion BF(4-). Our results reveal a significant contribution to
      nanocluster stability from the traditionally weakly coordinating BF(4-) in high
      dielectric constant solvents, such as propylene carbonate. Literature claims of
      solvent-only nanocluster stabilization are not supported by our findings.
      Overall, DLVO (Derjaugin-Landau-Verwey-Overbeek) theory of colloidal stability is
      supported and found to apply to even traditionally weakly coordinating anions.

PMID- 16999437
TI  - Characterization of the particulate methane monooxygenase metal centers in
      multiple redox states by X-ray absorption spectroscopy.
AB  - The integral membrane enzyme particulate methane monooxygenase (pMMO) converts
      methane, the most inert hydrocarbon, to methanol under ambient conditions. The
      2.8-A resolution pMMO crystal structure revealed three metal sites: a mononuclear
      copper center, a dinuclear copper center, and a nonphysiological mononuclear zinc
      center. Although not found in the crystal structure, solution samples of pMMO
      also contain iron. We have used X-ray absorption spectroscopy to analyze the
      oxidation states and coordination environments of the pMMO metal centers in as
      isolated (pMMO(iso)), chemically reduced (pMMO(red)), and chemically oxidized
      (pMMO(ox)) samples. X-ray absorption near-edge spectra (XANES) indicate that
      pMMO(iso) contains both Cu(I) and Cu(II) and that the pMMO Cu centers can undergo
      redox chemistry. Extended X-ray absorption fine structure (EXAFS) analysis
      reveals a Cu-Cu interaction in all redox forms of the enzyme. The Cu-Cu distance
      increases from 2.51 to 2.65 A upon reduction, concomitant with an increase in the
      average Cu-O/N bond lengths. Appropriate Cu2 model complexes were used to refine
      and validate the EXAFS fitting protocols for pMMO(iso). Analysis of Fe EXAFS data
      combined with electron paramagnetic resonance (EPR) spectra indicates that Fe,
      present as Fe(III), is consistent with heme impurities. These findings are
      complementary to the crystallographic data and provide new insight into the
      oxidation states and possible electronic structures of the pMMO Cu ions.

PMID- 16999439
TI  - Crystal growth and structure determination of oxygen-deficient Sr6Co5O15.
AB  - Large single crystals of oxygen-deficient Sr6Co5O(15-delta) compounds, i.e.,
      Sr6Co5O14.70 and Sr6Co4.9Ni0.1O14.36, were obtained by using K2CO3 flux in the
      presence of additives of transition metal oxides. The single-crystal structure
      determination shows that the structures of Sr6Co5O14.70 and Sr6Co4.9Ni0.1O14.36
      crystallize in the space group R and can be described as one-dimensional face
      sharing CoO3 polyhedral chains and Sr cation chains. Unlike the other known 2H
      perovskite-related oxides in which the polyhedral chains consist of octahedra
      (Oh) and trigonal prism (TP), the structure of Sr6Co5O14.70 and
      Sr6Co4.9Ni0.1O14.36 contain Oh and intermediate polyhedra (IP) and can be
      attributed to a general structure formula A6A'2B3O(15-delta), which is closely
      related to the known A6A'B4O15 phases by shifting of a B atom and the O3 triangle
      along the c axis. Further study on O3 reveals that this oxygen position splits
      into two independent positions, corresponding to polyhedral geometry of IP and
      TP, respectively. Therefore, the polyhedral chain in the structure should be more
      precisely described as a random composite of the 4Oh + TP and 3Oh + 2IP. This
      model is used to interpret the magnetic properties, although not quantitatively.
      The 4-D structure analysis was also conducted for both Sr6Co5O14.70 and
      Sr6Co4.9Ni0.1O14.36 with a commensurate modulated structure in a 4-D superspace
      group, R3m(00gamma)0s, gamma = p/k = 3/5. By considering the same 4-D superspace
      group R3m(00gamma)0s but different t-phases, one can understand the structure
      relationship between Sr6Co5O14.70 and Sr6Rh5O15.

PMID- 16999440
TI  - Hollow PbWO4 nanospindles via a facile sonochemical route.
AB  - Novel nanosized lead tungstate (PbWO4) hollow spindles were successfully
      synthesized, for the first time, via a Pluronic P123- (EO20PO70EO20-) assisted
      sonochemical process. The triblock copolymer acted as a structure-directing agent
      and played a key role in the formation of the hollow spindles. An in situ micelle
      templating mechanism has been proposed for the possible formation mechanism of
      the hollow nanostructure. The optical properties of the final products were
      investigated. It is exciting that the as-prepared PbWO4 hollow structure shows
      extraordinarily high room-temperature photoluminescence intensity compared to the
      solid structures.

PMID- 16999441
TI  - Neutron diffraction studies of U4O9: comparison with EXAFS results.
AB  - Conradson et al. have analyzed X-ray absorption fine-structure spectra of the UO2
      U4O9 system and concluded that oxygen atoms are incorporated in U4O9 as oxo
      groups with U-O distances in the range 1.72-1.76 A. They also found that the
      uranium sublattice consists of an ordered portion and an additional
      'spectroscopically silent' glassy portion. We have carried out studies of
      powdered U4O9 by neutron diffraction which contradict these conclusions from
      EXAFS measurements. Our analysis shows that there are no U-O bonds shorter than
      2.2 A and that U4O9 is crystallographically ordered with no evidence of a glassy
      structure.

PMID- 16999442
TI  - Synthesis, structure, and biological activity of ferrocenyl carbohydrate
      conjugates.
AB  - Seven ferrocenyl carbohydrate conjugates were synthesized. Coupling reactions of
      monosaccharide derivatives with ferrocene carbonyl chloride produced {6-N-(methyl
      2,3,4-tri-O-acetyl-6-amino-6-deoxy-alpha-D-glucopyranoside)}-1-ferrocene
      carboxamide (3), {1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1-ferrocene
      carboxylate (4), and {6-O-(1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose)}-1
      ferrocene carboxylate (5). Similarly, 1,1'-bis(carbonyl chloride)ferrocene was
      coupled with the appropriate sugars to produce the disubstituted analogues bis{6
      N-(methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-alpha-D-glucopyranoside)}-1,1'
      ferrocene carboxamide (8), bis{1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1,1'
      ferrocene carboxylate (9), and bis{6-O-(1,2,3,4-tetra-O-acetyl-beta-D
      glucopyranose)}-1,1'-ferrocene carboxylate (10). {6-N-(Methyl-6-amino-6-deoxy
      alpha-D-glucopyranoside)}-1-ferrocene carboxamide monohydrate (12) was
      synthesized via amide coupling of an activated ferrocenyl ester with the
      corresponding carbohydrate. All compounds were characterized by elemental
      analysis, 1H NMR spectroscopy, and mass spectrometry. X-ray crystallography
      confirmed the solid-state structure of three ferrocenyl carbohydrate conjugates:
      2-N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-D-glucopyranose)-1-ferrocene
      carboxamide (1), 1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D-glucopyranose)-1
      ferrocene carboxylate (2), and 12. The above compounds, along with bis{2-N
      (1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-D-glucopyranose)}-1,1'-ferrocene
      carboxamide (6), bis{1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D-glucopyranose)}
      1,1'-ferrocene carboxylate (7), and 2-N-(2-amino-2-deoxy-D-glucopyranose)-1
      ferrocene carboxamide (11) were examined for cytotoxicity in cell lines (L1210
      and HTB-129) and for antimalarial activity in Plasmodium falciparum strains (D10,
      3D7, and K1, a chloroquine-resistant strain). In general, the compounds were
      nontoxic in the human cell line tested (HTB-129), and compounds 4, 7, and 9
      showed moderate antimalarial activity in one or more of the P. falciparum
      strains.

PMID- 16999443
TI  - Preferred bonding motif for indium aminoethanethiolate complexes: structural
      characterization of (Me2NCH2CH2S)2InX/SR (X = Cl, I; R = 4-MeC6H4, 4-MeOC6H4).
AB  - The metathesis reaction of InCl3 with Me2NCH2CH2SNa or the redox reaction of
      indium metal with elemental iodine and the disulfide (Me2NCH2CH2S)2 yield the
      indium bis(thiolate) complexes (Me2NCH2CH2S)2InX [X = Cl (3) and I (4)],
      respectively. Compounds 3 and 4 may be further reacted with the appropriate
      sodium thiolate salts to afford the heteroleptic tris(thiolate) complexes
      (Me2NCH2CH2S)2InSR [R = 4-MeC6H4 (5), 4-MeOC6H4 (6), and Pr (7)]. Reaction of 2,6
      Me2C6H3SNa with 4 affords (Me2NCH2CH2S)2InS(2,6-Me2C6H3) (8), while no reaction
      is observed with 3, suggesting a greater reactivity for 4. All isolated compounds
      were characterized by elemental analysis, melting point, and Fourier transform IR
      and 1H and 13C{1H} NMR spectroscopies. X-ray crystallographic analyses of 3-6
      show a bicyclic arrangement and a distorted trigonal-bipyramidal geometry for In
      in all cases. The two sulfur and one halogen (3 and 4) or three sulfur (5 and 6)
      atoms occupy equatorial positions, while the nitrogen atoms of the chelating
      (dimethylamino)ethanethiolate ligands occupy the axial positions. The metric
      parameters of the (Me2NCH2CH2S)2In framework were found to change minimally upon
      variation of the X/SR ligand, while the solubility of the corresponding compounds
      in organic solvents varied greatly. 1H NMR studies in D2O showed that 6 and 7
      react slowly with an excess of the tripeptide l-glutathione and that the rate of
      reaction is affected by the pendant thiolate ligand -SR.

PMID- 16999445
TI  - Molecular structures of arachno-heteroboranes with decaborane frameworks: two Cs
      symmetrical azacarba- and carbathiaboranes.
AB  - The gas-phase structure of 6,9-CSB8H12 has been determined by electron
      diffraction and ab initio calculations, and that of 6,9-CNB8H13 has also been
      calculated. The accuracy of each structure has been confirmed by 11B NMR
      calculations. The position of the sulfur atom is very close to that of the boron
      atom occupying the equivalent position in the parent molecule [B10H14](2-),
      reflecting the similarity of sizes of sulfur and boron atoms. The nitrogen and
      carbon atoms, on the other hand, lie much closer to the centers of the cages. The
      B8-X9-B10 angles increase from 98.7 degrees for X = S to 122.8 degrees for X = N.
      There are also large changes in relative lengths of bonds, with some bonds
      lengthening by up to 14.6 pm on introduction of a sulfur atom.

PMID- 16999444
TI  - Steric effects in the aerobic oxidation of pi-allylnickel(II) complexes with N
      heterocyclic carbenes.
AB  - Pi-allylchloro(NHC)nickel(II) complexes were synthesized and their reactions with
      O2 were studied. Ligand steric effects were found to determine the difference
      between rapid oxidation of the allyl group to produce bis-mu-hydroxonickel
      complexes and no observable reaction. The ability of the metal-NHC bond to rotate
      correlates with the ability of the complex to react with O2. In the limiting
      cases, conformationally restricted complexes are stable to O2 and complexes with
      rapid Ni-NHC bond rotation react rapidly with O2. Complexes with intermediate
      conformational flexibility were found to exhibit lesser reactivity with O2. On
      the basis of the observed inertness of complexes with saddle-shaped ligands to
      O2, we propose the adoption of a nonplanar geometry upon reaction with O2 to be
      required. The issue of conformational flexibility versus rigidity is expected to
      directly impact the catalytic behavior of metal-NHC complexes.

PMID- 16999446
TI  - Syntheses, spectroscopies and structures of molybdenum(VI) complexes with
      homocitrate.
AB  - Initial investigations into the possible role of homocitric acid in iron
      molybdenum cofactor (FeMo-co) of nitrogenase lead us to isolate and characterize
      two tetrameric molybdate(VI) species. The complexes K2(NH4)2[(MoO2)4O3(R,S
      Hhomocit)2].6H2O (1) and K5[(MoO2)4O3(R,S-Hhomocit)2]Cl.5H2O (2) (homocitric acid
      = H4homocit, C7H10O7) are prepared from the reactions of acyclic homocitric acid
      and molybdates, which represent the first synthetic structural examples of
      molybdenum homocitrate complexes. The homocitrate ligand trapped by tetranuclear
      molybdate coordinates to the molybdenum(VI) atom through alpha-alkoxy and alpha-,
      beta-carboxy groups. The physical properties, structural parameters, and their
      possible biological relevances are discussed.

PMID- 16999447
TI  - Organically directed iron sulfate chains: structural diversity based on hydrogen
      bonding interactions.
AB  - Six organically directed 1-D iron sulfates hydrated and hydrolyzed to different
      extents have been prepared hydrothermally. [C2H10N2]1.5[Fe(SO4)(3)].2H2O (I),
      [C2H10N2][Fe(SO4)2(OH)].H2O (II), [C6H18N2]0.5[Fe(SO4)2(H2O)2] (III), and
      [C6H18N2]0.5[Fe2(SO4)(H2O)4(OH)].H2O (V) possess the linear topological
      structures observed in ferrinatrite, sideronatrite, krohnkite, and copiapite
      minerals, respectively. [C4H12N2][Fe2(SO4)3(OH)2(H2O)2].H2O (IV) shows a novel
      linear structure that can be regarded as a hybrid of the tancoite and butlerite
      types. [C6N4H22]0.5[Fe(SO4)2(OH)].2H2O (VI) adopts a cis configuration, compared
      with II, to give a rare inorganic helical iron sulfate chain which is a new
      member of the organically directed transitional metal sulfates. The results
      reveal that the starting molar proportion of the reactants and the type of amines
      are critical for the structural motif. There is an obvious relationship between
      the constitution of chains and the type of amino groups, involving the amount of
      N-H...O hydrogen bonds.

PMID- 16999450
TI  - Therapeutic monitoring of antiepileptic drugs during pregnancy and in the
      postpartum period: is it useful?
AB  - As in all patient populations, epilepsy is common in pregnant women.
      Consequently, approximately 1 in 200 pregnancies is exposed to antiepileptic
      drugs (AEDs). Although exposure to AEDs in utero has been associated with an
      increased risk of major fetal malformations, most women with epilepsy require
      medication throughout pregnancy, since seizures themselves may be potentially
      harmful not only for the mother but also for the developing fetus. Physiological
      changes during pregnancy result in a reduction in the serum concentrations of
      most AEDs, particularly in late pregnancy. Changes in protein binding lead to a
      greater reduction in total than free (active) drug concentrations.
      Pharmacokinetic changes in pregnancy show interindividual variability and are not
      well understood for most newer AEDs. However, recent studies have shown that
      changes in lamotrigine clearance are particularly marked, with increases in each
      trimester and a significant fall in plasma concentrations, leading to consequent
      breakthrough seizures in some women. Concentrations may then rise precipitously
      after delivery, leading to symptoms of lamotrigine toxicity. Therapeutic drug
      monitoring could theoretically guide adjustment of AED dosage to achieve good
      seizure control while minimising fetal exposure, although there are several
      limitations to such monitoring. Firstly, there are wide interindividual
      variations in serum drug concentrations, with seizure control often correlating
      poorly with a given therapeutic range. Secondly, therapeutic ranges have not been
      well defined for newer AEDs and their measurement is often not always available.
      Thirdly, for highly protein-bound drugs, although measurement of free drug
      concentrations may more accurately reflect drug availability during pregnancy
      than total drug concentrations, assays for this are not always available and may
      be unreliable. Thus, it may be useful, prior to pregnancy, to establish the total
      and free drug concentrations required to achieve optimal seizure control in a
      given individual. Regular monitoring of AEDs has been advocated in each trimester
      and shortly after delivery, with adjustment of dosage to avoid seizure
      precipitation during pregnancy or symptoms of toxicity after birth. More frequent
      monitoring has been recommended for lamotrigine. However, aggressive drug
      monitoring of any AED has yet to be proven to be effective in improving seizure
      control or care. Furthermore, higher doses may be associated with a greater
      potential for teratogenicity and it is not yet known whether longer term adverse
      effects may be related to in utero exposure in the latter half of pregnancy.
      There is limited evidence about the relationship of maternal serum drug
      concentrations and teratogenicity. While there is a theoretical role for
      therapeutic drug monitoring in improving the risk-to-benefit ratio of AED therapy
      during pregnancy, there are many practical limitations. Future work is needed to
      clarify its role in improving seizure control during pregnancy and identifying
      serum drug concentrations that may be considered safe for fetal exposure.

PMID- 16999451
TI  - Melanin-concentrating hormone MCH1 receptor antagonists: a potential new approach
      to the treatment of depression and anxiety disorders.
AB  - Melanin-concentrating hormone (MCH) is a cyclic 19-amino-acid neuropeptide that
      has been considered to play a key role in the regulation of feeding and energy
      homeostasis. To date, two receptor subtypes for MCH (designated MCH(1) and
      MCH(2)) have been identified; the MCH(1) receptor has been proposed to mediate
      the physiological functions of MCH in rodents. In addition to the crucial roles
      of MCH in feeding behaviour, anatomical and neurochemical studies suggest that
      the MCH/MCH(1) system is involved in the regulation of emotion and stress
      responses. This assumption has been supported by a recent series of neurochemical
      and behavioural studies. Indeed, several lines of evidence show that MCH
      activates stress responses and induces depressive- and anxiety-like behaviours,
      while the blockade of MCH(1) receptors results in antidepressant and anxiolytic
      effects in various rodent models. Moreover, MCH may decrease reward activity
      while increasing hypothalamus-pituitary adrenal axis activity, both of which may
      underlie the neurochemical mechanisms of the depression and anxiety-like effects
      induced by MCH. The effects of MCH(1) receptor antagonists in animal models,
      together with their rapid onset of effect and lack of adverse CNS effects,
      suggest that they deserve further investigation as potential new treatments for
      depression and anxiety disorders.

PMID- 16999452
TI  - Migraine in children and adolescents: a guide to drug treatment.
AB  - Migraine is a common disorder in children and adolescents, with a prevalence of 5
      and 10%, respectively. Some patients may have recognisable factors that trigger
      or aggravate migraine attacks, such as flickering or bright lights, strong smells
      and noise, and where possible these should be avoided. It is also wise to
      maintain a lifestyle where children receive regular meals and get sufficient
      sleep. If used, acute pharmacological treatment should be given at the onset of
      an attack, followed by a rest or sleep. According to recent literature,
      paracetamol (acetaminophen) and ibuprofen can be recommended for the acute
      treatment of migraine attacks in children and adolescents, and sumatriptan nasal
      spray can be recommended for adolescents. The oral formulation of sumatriptan has
      not shown efficacy in paediatric patients, and the subcutaneous injection,
      although somewhat effective, is not an ideal formulation for this patient group.
      There are too few data on the efficacy of the other 'triptans' to recommend their
      use in children and adolescents. There are less data on the use of prophylactic
      drugs in paediatric patients. In systematic studies, only flunarizine, which is
      not available in many countries, and propranolol have been found to be effective.
      A pilot placebo-controlled study suggests that topiramate might also be
      effective. Several other agents are commonly used to prevent migraine attacks in
      children (e.g. amitriptyline, valproic acid [sodium valproate]) despite a lack of
      robust research into their efficacy.

PMID- 16999453
TI  - Use of neostigmine in the management of acute postoperative pain and labour pain:
      a review.
AB  - Neostigmine is a parasympathomimetic agent that has been recently investigated
      for use as an adjunct analgesic agent in the perioperative and peripartum period.
      A number of studies have investigated the intrathecal, epidural, caudal and intra
      articular routes of administration of this agent, as well as the addition of
      neostigmine to local anaesthetics used for brachial plexus block and intravenous
      regional anaesthesia. While the intrathecal administration of neostigmine
      produced useful analgesic effects in the postoperative period in some studies,
      the high incidence of adverse events, mainly nausea and vomiting, limit the
      clinical usefulness of this route of administration. Several studies investigated
      the postoperative analgesic effects of epidural neostigmine using a number of
      different regimens. Overall, this route of administration appeared to improve
      postoperative analgesia in most studies without increasing the incidence of
      adverse events, and merits further research. Neuraxial administration of
      neostigmine appears to be safe in the obstetric population, with no reported
      adverse effects in the mother or fetus. While intrathecal administration is
      limited by a high incidence of nausea and vomiting in this patient population,
      the epidural route appears more promising and requires further investigation. The
      addition of neostigmine to caudal local anaesthetics was associated with improved
      postoperative analgesia in a number of studies. A dose of 2 microg/kg proved to
      be effective in several studies but was associated with an increased incidence of
      vomiting in some studies. Intra-articular administration of neostigmine 500microg
      produced a useful analgesic effect in the postoperative period in several studies
      and was not associated with an increase in the incidence of adverse effects.
      Studies investigating the efficacy of adding neostigmine to the local
      anaesthetics used for brachial plexus block and intravenous regional anaesthesia
      reported conflicting results. Further studies are required to determine the place
      of the administration of neostigmine by these routes.

PMID- 16999456
TI  - Spectroscopic studies of fractal aggregates of silver nanospheres undergoing
      local restructuring.
AB  - We present an experimental spectroscopic study of large random colloidal
      aggregates of silver nanoparticles undergoing local restructuring. We argue that
      such well-known phenomena as strong fluctuation of local electromagnetic fields,
      appearance of "hot spots" and enhancement of nonlinear optical responses depend
      on the local structure on the scales of several nanosphere diameters, rather than
      the large-scale fractal geometry of the sample.

PMID- 16999455
TI  - Changes in metabolite ratios after treatment with rivastigmine in Alzheimer's
      disease: a nonrandomised controlled trial with magnetic resonance spectroscopy.
AB  - BACKGROUND: Alzheimer's disease is associated with abnormalities in the levels of
      some brain metabolites, including decreases in N-acetyl-aspartate (NAA) and
      increases in myo-inositol and choline levels. Cholinesterase inhibitors have
      proven modest effects on cognition in patients with mild or moderate Alzheimer's
      disease; however, there is little information on the effects of these drugs on
      metabolic parameters in the brain. Magnetic resonance spectroscopy (MRS) provides
      a method of determining changes in such parameters. OBJECTIVE: To assess the
      effect of rivastigmine on metabolite levels in different areas of the brain, and
      whether changes in metabolite levels correlate with clinical outcome, in patients
      with Alzheimer's disease compared with untreated patients with Alzheimer's
      disease. METHODS: Twenty-four consecutive patients with mild or moderate
      Alzheimer's disease were enrolled in the study and were treated with rivastigmine
      at a target dosage of 12 mg/day for 4 months. A comparison group of ten
      consecutive untreated patients with Alzheimer's disease with similar cognitive
      impairment to the treatment group were also enrolled. Each patient underwent
      assessment using the Mini-Mental State Examination (Spanish version), the Blessed
      Dementia Rating Scale, the Clinical Dementia Rating scale, the Interview for
      Deterioration in Daily living activities in Dementia, the Alzheimer's Disease
      Assessment Scale cognitive and noncognitive subscales, and single-voxel MRS of
      the frontal, parietal and occipital cortices of the brain to assess levels of
      brain metabolites (NAA, creatine, choline and myo-inositol) and their ratios to
      creatine. All assessments were performed at baseline and after 4 months of
      treatment with rivastigmine, and at baseline and 1 month later in the comparison
      group. RESULTS: Globally, although there was some mean improvement, no
      significant changes in the cognitive and noncognitive scale scores between
      baseline and post-treatment assessments were seen in patients who received
      rivastigmine. A significant increase in the NAA/creatine ratio in the frontal
      cortex (1.23 at baseline vs 1.3 after treatment; p = 0.026) and in the myo
      inositol/creatine ratio in the occipital cortex (0.61 vs 0.65; p = 0.009) was
      seen in rivastigmine-treated patients. No other significant changes in the
      metabolite levels or their ratios to creatine were seen in these patients. After
      correction for multiple comparisons, the significant effects disappeared. Only in
      the frontal cortex did the changes in metabolite ratios correlate with changes on
      the clinical scales. In the comparison group, no significant differences between
      the metabolite levels or ratios to creatine seen with the two scans were
      detected. CONCLUSION: Treatment with rivastigmine showed modest neuronal
      functional recovery in the frontal cortex only (being able to reverse disease
      related decreases in NAA/creatine ratio in this area but unable to affect the
      disease-related increase in myo-inositol/creatine ratio in any cortex). Since the
      modest clinical changes correlated with the small changes in the metabolite
      rates, MRS could be useful in monitoring response to current or future treatments
      for Alzheimer's disease.

PMID- 16999454
TI  - Children with schizophrenia: clinical picture and pharmacological treatment.
AB  - Awareness of childhood-onset schizophrenia is rapidly increasing, with a more
      precise definition now available of the clinical picture and early signs, the
      outcome and the treatment strategies. Premorbid developmental impairments,
      including language, motor and social deficits, are more frequent and more
      pronounced in earlier- than in later-onset forms of schizophrenia. This 'pan
      dysmaturation' is reported from the first months of life in more than half of the
      children who will develop childhood-onset schizophrenia, and it suggests a more
      severe and early disruption of brain development compared with the adolescent-
      and adult-onset disorder. The insidious onset in at least 75% of children, the
      high rates of premorbid problems and the hesitancy on the part of clinicians to
      make a diagnosis of schizophrenia in a child usually delay the recognition of the
      syndrome. Elementary auditory hallucinations are the most frequent positive
      symptom, while visual and tactile hallucinations are rarer. Delusions are less
      complex than in adolescents and are usually related to childhood themes. Negative
      symptoms are largely predominant, namely flat or inappropriate affect. A marked
      deterioration from the previous level of functioning is present in all these
      children, and an impaired outcome is reported in approximately 50-60% of them.
      The main diagnostic challenges are with differentiating childhood-onset
      schizophrenia from affective disorders (both depression and bipolar disorder)
      with psychotic symptoms, pervasive developmental disorders and severe personality
      disorders. Post-traumatic stress disorder and obsessive-compulsive disorder
      without insight may also be misdiagnosed as schizophrenia. Furthermore,
      approximately 10% of children from the community report nonpsychotic
      hallucinations or delusions. Finally, children with atypical psychotic features
      that do not strictly fit diagnostic criteria for schizophrenia have been
      described, and new labels have been proposed to categorise these clinical
      patterns, such as multidimensionally impaired disorder and multiple complex
      developmental disorder. In the context of a multimodal approach, including
      behavioral, social, scholastic and familial interventions, a pharmacological
      treatment is usually the core treatment. Available experience from the few
      controlled studies, open studies and case reports on pharmacotherapy in children
      with schizophrenia aged <12 years is critically analysed in this review, with
      particular reference to the use of atypical antipsychotics in clinical practice.
      To date, the major evidence supports the efficacy of risperidone and olanzapine,
      while clozapine seems an effective option in treatment-refractory cases.
      Published experience with newer atypical antipsychotics (quetiapine, ziprasidone,
      aripiprazole) is still lacking in this age range. Safety data (namely
      extrapyramidal symptoms, weight gain, hyperprolactinaemia, haematological adverse
      effects, seizures, hepatotoxicity, metabolic effects, neuroleptic malignant
      syndrome and cardiovascular effects) are reviewed and discussed, along with
      strategies for management.

PMID- 16999457
TI  - Infrared spectroscopy of hydrated sulfate dianions.
AB  - We report the first infrared spectra of multiply-charged anions in the gas phase.
      The spectra of SO(4) (2-)(H(2)O)(n), with n=3-24, show four main bands assigned
      to two vibrations of the dianionic core, the water bending mode, and solvent
      libration. The triply degenerate SO(4) (2-) antisymmetric stretch vibration
      probes the local solvent symmetry, while the solvent librational band is
      sensitive to the hydrogen bonding network. The spectra and accompanying
      electronic structure calculations indicate a highly symmetric structure for the
      n=6 cluster and closure of the first solvation shell at n=12.

PMID- 16999458
TI  - Vibrational anharmonicity effects in electronic tunneling through molecular
      bridges.
AB  - Effects of anharmonic bridge vibrations on electronic tunneling in donor-bridge
      acceptor complexes are studied using a model of anharmonic bridge vibration
      coupled nonlinearly to an electronic degree of freedom. An anharmonicity
      parameter is introduced, enabling to reproduce the standard harmonic model with
      linear coupling as a limiting case. The frequency of electronic tunneling
      oscillations between the donor and acceptor sites is shown to be sensitive to the
      nuclear anharmonicity, where stretching and compression modes have an opposite
      effect on the electronic frequency. This phenomenon, that cannot be accounted for
      within the harmonic approximation, is analyzed and explained.

PMID- 16999459
TI  - Formation of supramolecular permethrin/beta-cyclodextrin nanorods.
AB  - Molecular dynamics simulations along with scanning tunneling microscopy (STM)
      imaging demonstrate the formation of a novel type of nanorods, with a stable
      [permethrin(beta-CD)(2)](n) structure in which the host:guest ratio is 2:1 and
      n=21-27 giving a length of approximately 30.0-38.5 nm and an average diameter of
      approximately 1.5 nm, self-assembled from an inclusion complex composed of
      permethrin and biocompatible beta-cyclodextrin.

PMID- 16999460
TI  - Bias annealing: a method for obtaining transition paths de novo.
AB  - Computational studies of dynamics in complex systems require means for generating
      reactive trajectories with minimum knowledge about the processes of interest.
      Here, we introduce a method for generating transition paths when an existing one
      is not already available. Starting from biased paths obtained from steered
      molecular dynamics, we use a Monte Carlo procedure in the space of whole
      trajectories to shift gradually to sampling an ensemble of unbiased paths.
      Application to basin-to-basin hopping in a two-dimensional model system and
      nucleotide-flipping by a DNA repair protein demonstrates that the method can
      efficiently yield unbiased reactive trajectories even when the initial steered
      dynamics differ significantly. The relation of the method to others and the
      physical basis for its success are discussed.

PMID- 16999461
TI  - New evaluation of reconstructed spatial distribution function from radial
      distribution functions.
AB  - Although three dimensional (3D) solvation structure is much more informative than
      one dimensional structure, its evaluation is difficult experimentally and
      theoretically. In our previous Communication [Yokogawa et al., J. Chem. Phys.
      123, 211102 (2005)], we proposed a new method to present reconstructed spatial
      distribution function (RC-SDF) from a set of radial distribution functions
      (RDFs). In this article, we successfully extended the method more accurately with
      new basis sets. This new method was applied to two liquid solvation structures,
      methanol and dimethyl sulfoxide, as examples. Their RC-SDFs evaluated here
      clearly show that the former solvation structure is well defined while the latter
      one is broad, which agrees well with the SDFs calculated directly from molecular
      dynamics simulations. These results indicate that the method can reproduce well
      these 3D solvation structures in reasonable computational cost.

PMID- 16999462
TI  - On the enhanced sampling over energy barriers in molecular dynamics simulations.
AB  - We present here calculations of free energies of multidimensional systems using
      an efficient sampling method. The method uses a transformed potential energy
      surface, which allows an efficient sampling of both low and high energy spaces
      and accelerates transitions over barriers. It allows efficient sampling of the
      configuration space over and only over the desired energy range(s). It does not
      require predetermined or selected reaction coordinate(s). We apply this method to
      study the dynamics of slow barrier crossing processes in a disaccharide and a
      dipeptide system.

PMID- 16999463
TI  - Two-dimensional quantum propagation using wavelets in space and time.
AB  - A recent method for solving the time-dependent Schrodinger equation has been
      developed using expansions in compact-support wavelet bases in both space and
      time [H. Wang et al., J. Chem. Phys. 121, 7647 (2004)]. This method represents an
      exact quantum mixed time-frequency approach, with special initial temporal
      wavelets used to solve the initial value problem. The present work is a first
      extension of the method to multiple spatial dimensions applied to a simple two
      dimensional (2D) coupled anharmonic oscillator problem. A wavelet-discretized
      version of norm preservation for time-independent Hamiltonians discovered in the
      earlier one-dimensional investigation is verified to hold as well in 2D and, by
      implication, in higher numbers of spatial dimensions. The wavelet bases are not
      restricted to rectangular domains, a fact which is exploited here in a 2D
      adaptive version of the algorithm.

PMID- 16999464
TI  - An efficient sampling algorithm for variational Monte Carlo.
AB  - We propose a new algorithm for sampling the N-body density mid R:Psi(R)mid
      R:(2)R(3N)mid R:Psimid R:(2) in the variational Monte Carlo framework. This
      algorithm is based upon a modified Ricci-Ciccotti discretization of the Langevin
      dynamics in the phase space (R,P) improved by a Metropolis-Hastings accept/reject
      step. We show through some representative numerical examples (lithium, fluorine,
      and copper atoms and phenol molecule) that this algorithm is superior to the
      standard sampling algorithm based on the biased random walk (importance
      sampling).

PMID- 16999465
TI  - Approximate first passage time distribution for barrier crossing in a double well
      under fractional Gaussian noise.
AB  - The distribution of waiting times, f(t), between successive turnovers in the
      catalytic action of single molecules of the enzyme beta-galactosidase has
      recently been determined in closed form by Chaudhury and Cherayil [J. Chem. Phys.
      125, 024904 (2006)] using a one-dimensional generalized Langevin equation (GLE)
      formalism in combination with Kramers' flux-over-population approach to barrier
      crossing dynamics. The present paper provides an alternative derivation of f(t)
      that eschews this approach, which is strictly applicable only under conditions of
      local equilibrium. In this alternative derivation, a double well potential is
      incorporated into the GLE, along with a colored noise term representing protein
      conformational fluctuations, and the resulting equation transformed approximately
      to a Smoluchowski-type equation. f(t) is identified with the first passage time
      distribution for a particle to reach the barrier top starting from an equilibrium
      distribution of initial points, and is determined from the solution of the above
      equation using local boundary conditions. The use of such boundary conditions is
      necessitated by the absence of definite information about the precise nature of
      the boundary conditions applicable to stochastic processes governed by non
      Markovian dynamics. f(t) calculated in this way is found to have the same
      analytic structure as the distribution calculated by the flux-over-population
      method.

PMID- 16999466
TI  - Hamiltonian formalism for semiflexible molecules in Cartesian coordinates.
AB  - The article gives a concise description of Hamiltonian dynamics and thermal
      averages of semiflexible molecules in Cartesian coordinates. Using the concept of
      constrained inverse matrices introduced by Bott and Duffin [Trans. Am. Math. Soc.
      74, 99 (1953)] explicit expressions are derived for the constrained Hamiltonian,
      the corresponding equations of motion, and the momentum partition function. In
      this context Fixman-type corrections of constrained configurational averages are
      derived for different forms of the constraints. It is shown that the use of mass
      weighted coordinates leads to a nonbiased sampling of constrained configurational
      averages in Cartesian coordinates. The formalism allows moreover to define and to
      calculate effective masses arising in thermal velocity averages of atoms in
      semiflexible molecules. These effective masses are identical to the corresponding
      Sachs-Teller recoil masses, which are here generalized to the case of only
      partially rigid molecules.

PMID- 16999467
TI  - Two-electron distribution functions and short-range electron correlations of
      atoms and molecules by first principles T-matrix calculations.
AB  - The accurate first principles description of the correlations between electrons
      has been a topic of interest in molecular physics. We have reported in our
      previous paper [J. Chem. Phys. 123, 144112 (2005)] that the T matrix, which is
      the ladder diagrams up to the infinite order, can accurately represent the short
      range electron correlations while calculating the double ionization energy
      spectra of atoms and molecules. In this paper, we calculate the two-electron
      distribution functions of real systems (Ar, CO, CO(2), and C(2)H(2)) from the
      eigenvalue equation associated with the Bethe-Salpeter equation for the T matrix
      by beginning with the local density approximation of the density functional
      theory and the GW approximation. We found that when the interelectron distance is
      very small, the Coulomb hole appears between antiparallel spin electrons due to
      the short-range repulsive Coulomb interaction. The resulting two-electron
      distribution functions clearly show the Coulomb hole.

PMID- 16999468
TI  - Single vibronic level emission spectroscopic studies of the ground state energy
      levels and molecular structures of jet-cooled HGeBr, DGeBr, HGeI, and DGeI.
AB  - Single vibronic level dispersed fluorescence spectra of jet-cooled HGeBr, DGeBr,
      HGeI, and DGeI have been obtained by laser excitation of selected bands of the A
      (1)A(")-X (1)A(') electronic transition. The measured ground state vibrational
      intervals were assigned and fitted to anharmonicity expressions, which allowed
      the harmonic frequencies to be determined for both isotopomers. In some cases,
      lack of a suitable range of emission data necessitated that some of the
      anharmonicity constants and vibrational frequencies be estimated from those of
      HGeClDGeCl and the corresponding silylenes (HSiX). Harmonic force fields were
      obtained for both molecules, although only four of the six force constants could
      be determined. The ground state effective rotational constants and force field
      data were combined to calculate average (r(z)) and approximate equilibrium (r(e)
      (z)) structures. For HGeBr r(e) (z)(GeH)=1.593(9) A, r(e) (z)(GeBr)=2.325(21) A,
      and the bond angle was fixed at our CCSD(T)/aug-cc-pVTZ ab initio value of 93.6
      degrees . For HGeI we obtained r(e) (z)(GeH)=1.589(1) A, r(e) (z)(GeI)=2.525(5)
      A, and bond angle=93.2 degrees . Franck-Condon simulations of the emission
      spectra using ab initio Cartesian displacement coordinates reproduce the observed
      intensity distributions satisfactorily. The trends in structural parameters in
      the halogermylenes and halosilylenes can be readily understood based on the
      electronegativity of the halogen substituent.

PMID- 16999469
TI  - State-to-state rotational transitions in H2+H2 collisions at low temperatures.
AB  - We present quantum mechanical close-coupling calculations of collisions between
      two hydrogen molecules over a wide range of energies, extending from the
      ultracold limit to the superthermal region. The two most recently published
      potential energy surfaces for the H(2)-H(2) complex, the so-called Diep-Johnson
      (DJ) [J. Chem. Phys. 112, 4465 (2000); 113, 3480 (2000)] and Boothroyd-Martin
      Keogh-Peterson (BMKP) [J. Chem. Phys. 116, 666 (2002)] surfaces, are
      quantitatively evaluated and compared through the investigation of rotational
      transitions in H(2)+H(2) collisions within rigid rotor approximation. The BMKP
      surface is expected to be an improvement, approaching chemical accuracy, over all
      conformations of the potential energy surface compared to previous calculations
      of H(2)-H(2) interaction. We found significant differences in rotational
      excitation/deexcitation cross sections computed on the two surfaces in collisions
      between two para-H(2) molecules. The discrepancy persists over a large range of
      energies from the ultracold regime to thermal energies and occurs for several low
      lying initial rotational levels. Good agreement is found with experiment B. Mate
      et al., [J. Chem. Phys. 122, 064313 (2005)] for the lowest rotational excitation
      process, but only with the use of the DJ potential. Rate coefficients computed
      with the BMKP potential are an order of magnitude smaller.

PMID- 16999470
TI  - Photodetachment and photofragmentation pathways in the [(CO2)2(H2O)m]- cluster
      anions.
AB  - The mass-selected [(CO(2))(2)(H(2)O)(m)](-) cluster anions are studied using a
      combination of photoelectron imaging and photofragment mass spectroscopy at 355
      nm. Photoelectron imaging studies are carried out on the mass-selected parent
      cluster anions in the m=2-6 size range; photofragmentation results are presented
      for m=3-11. While the photoelectron images suggest possible coexistence of the
      CO(2) (-)(H(2)O)(m)CO(2) and (O(2)CCO(2))(-)(H(2)O)(m) parent cluster structures,
      particularly for m=2 and 3, only the CO(2) (-) based clusters are both required
      and sufficient to explain all fragmentation pathways for m>/=3. Three types of
      anionic photofragments are observed: CO(2) (-)(H(2)O)(k), O(-)(H(2)O)(k), and
      CO(3) (-)(H(2)O)(k), k</=m, with their yields varying depending on the parent
      cluster size. Of these, only CO(2) (-)(H(2)O)(k) can potentially result from
      (O(2)CCO(2))(-)(H(2)O)(m) parent structures, although an alternative mechanism,
      involving the dissociation and recombination of the CO(2) (-) cluster core, is
      possible as well. The O(-)(H(2)O)(k) and CO(3) (-)(H(2)O)(k) channels are
      believed to be triggered by the dissociation of the CO(2) (-) cluster core. In
      the CO(3) (-)(H(2)O)(k) channel, seen only in the range of m=3-6, the CO(2) (-)
      core dissociation is followed by an intracluster association of nascent O(-) with
      the solvent CO(2). This channel's absence in larger clusters (m>6) is attributed
      to hindrance from the H(2)O molecules.

PMID- 16999472
TI  - Coexistence of ferroelectricity and ferromagnetism in tantalum clusters.
AB  - The atomic and electronic structures of Ta(N) (N=2-23) clusters have been
      determined in the framework of pseudopotential density-functional calculations,
      based upon an unbiased global search with guided simulated annealing to an
      empirical potential. It is found that the ground-state structures of Ta(N) are
      very similar to those of Nb(N), showing no preference for the icosahedral growth.
      Also, a size- and structure-dependent ferroelectricity is found in these tantalum
      clusters. More importantly, it is found that the ferroelectricity and
      ferromagnetism can coexist in the homogeneous transition-metal cluster, offering
      a possibility to obtain a new type of "multiferroic" materials composed of the
      clusters. Finally, the far-infrared spectroscopy is suggested to be an efficient
      tool to distinguish the ferroelectric clusters.

PMID- 16999473
TI  - Near-resonant vibration-to-vibration energy transfer in the NO+-N2 collisions.
AB  - First principles model calculations of the vibration-to-vibration (VV) energy
      transfer (ET) processes NO(+)(nu=1)+N(2)(nu=n-1)-->NO(+)(nu=0)+N(2)(nu=n)+(28.64n
      14.67) cm(-1) and NO(+)(nu=n)+N(2)(nu=0)-->NO(+)(nu=n-1)+N(2)(nu=1)+(32.52(n
      1)+13.97) cm(-1) for n=1-3 in the 300-1000 K temperature range are performed. The
      VV ET probability is computed for three mechanisms: (1) The charge on NO(+)
      acting on the average polarizability of N(2) induces a dipole moment in N(2)
      which then interacts with the permanent dipole moment of NO(+) to mediate the
      energy transfer. (2) The charge on NO(+) acting on the anisotropic polarizability
      of N(2) induces a dipole moment in N(2) which then interacts with the permanent
      dipole moment of NO(+) to mediate the energy transfer. (3) The dipole moment of
      NO(+) interacts with the quadrupole moment of N(2) to mediate the energy
      transfer. Because the probability amplitudes of the second and third mechanisms
      add coherently the ET probability for these two mechanisms is given as a single
      number. The probability of energy transfer per collision is in the 5 x 10(-3)
      range. The results of this calculation are compared with the available
      experimental data. This calculation should help quantify the role of NO(+) in the
      energy budget of the upper atmosphere.

PMID- 16999471
TI  - C1s and O1s photoelectron satellite spectra of CO with symmetry-dependent
      vibrational excitations.
AB  - The photoelectron shake-up satellite spectra that accompany the C1s and O1s main
      lines of carbon monoxide have been studied by a combination of high-resolution x
      ray photoelectron spectroscopy and accurate ab initio calculations. The symmetry
      adapted cluster-expansion configuration-interaction general-R method
      satisfactorily reproduces the satellite spectra over a wide energy region, and
      the quantitative assignments are proposed for the 16 and 12 satellite bands for
      C1s and O1s spectra, respectively. Satellite peaks above the pi(-1)pi(*)
      transitions are mainly assigned to the Rydberg excitations accompanying the inner
      shell ionization. Many shake-up states, which interact strongly with three
      electron processes such as pi(-2)pi(*2) and n(-2)pi(*2), are calculated in the
      low-energy region, while the continuous Rydberg excitations are obtained with
      small intensities in the higher-energy region. The vibrational structures of low
      lying shake-up states have been examined for both C1s and O1s ionizations. The
      vibrational structures appear in the low-lying C1s satellite states, and the
      symmetry-dependent angular distributions for the satellite emission have enabled
      the Sigma and Pi symmetries to be resolved. On the other hand, the potential
      curves of the low-lying O1s shake-up states are predicted to be weakly bound or
      repulsive.

PMID- 16999474
TI  - Isomerization dynamics and thermodynamics of ionic argon clusters.
AB  - The dynamics and thermodynamics of small Ar(n) (+) clusters, n=3, 6, and 9, are
      investigated using molecular dynamics (MD) and exchange Monte Carlo (MC)
      simulations. A diatomic-in-molecule Hamiltonian provides an accurate model for
      the electronic ground state potential energy surface. The microcanonical caloric
      curves calculated from MD and MC methods are shown to agree with each other,
      provided that the rigorous conservation of angular momentum is accounted for in
      the phase space density of the MC simulations. The previously proposed projective
      partition of the kinetic energy is used to assist MD simulations in interpreting
      the cluster dynamics in terms of inertial, internal, and external modes. The
      thermal behavior is correlated with the nature of the charged core in the cluster
      by computing a dedicated charge localization order parameter. We also perform
      systematic quenches to establish a connection with the various isomers. We find
      that the Ar(3) (+) cluster is very stable in its linear ground state geometry up
      to about 300 K, and then isomerizes to a T-shaped isomer in which a quasineutral
      atom lies around a charged dimer. In Ar(6) (+) and Ar(9) (+), the covalent trimer
      core is solvated by neutral atoms, and the weakly bound solvent shell melts at
      much lower energies, occasionally leading to a tetramer or pentamer core with
      weakly charged extremities. At high energies the core itself becomes metastable
      and the cluster transforms into Ar(2) (+) solvated by a fluid of neutral argon
      atoms.

PMID- 16999475
TI  - 2-pyridone: The role of out-of-plane vibrations on the S1<-->S0 spectra and S1
      state reactivity.
AB  - The S(1)<-->S(0) vibronic spectra of supersonic jet-cooled 2-pyridone [pyridin-2
      one (2PY)] and its N-H deuterated isotopomer (d-2PY) have been recorded by two
      color resonant two-photon ionization, laser-induced fluorescence and emission,
      and fluorescence depletion spectroscopies. By combining these methods, the B
      origin of 2PY at 0(0) (0)+98 cm(-1) and the bands at +218 and +252 cm(-1) are
      identified as overtones of the S(1) state out-of-plane vibrations nu(1) (') and
      nu(2) ('), as are the analogous bands of d-2PY. Anharmonic double-minimum
      potentials are derived for the respective out-of-plane coordinates that predict
      further nu(1) (') and nu(2) (') overtones and combinations, reproducing
      approximately 80% of the vibronic bands up to 600 cm(-1) above the 0(0) (0) band.
      The fluorescence spectra excited at the electronic origins and the nu(1) (') and
      nu(2) (') out-of-plane overtone levels confirm these assignments. The S(1)
      nonplanar minima and S(1)<--S(0) out-of-plane progressions are in agreement with
      the determination of nonplanar vibrationally averaged geometries for the 0(0) (0)
      and 0(0) (0)+98 cm(-1) upper states by Held et al. [J. Chem. Phys. 95, 8732
      (1991)]. The fluorescence lifetimes of the S(1) state vibrations show strong mode
      dependence: Those of the out-of-plane levels decrease rapidly above 200 cm(-1)
      excess vibrational energy, while the in-plane vibrations nu(5) ('), nu(8) ('),
      and nu(9) (') have longer lifetimes, although they are above or interspersed with
      the "dark" out-of-plane states. This is interpreted in terms of an S(1) (') state
      reaction with a low barrier towards a conical intersection with a prefulvenic
      geometry. Out-of-plane vibrational states can directly surmount this barrier,
      whereas in-plane vibrations are much less efficient in this respect. Analysis of
      the fluorescence spectra allows to identify nine in-plane S(0) (') state
      fundamentals, overtones of the S(0) state nu(1) (") and nu(2) (") out-of-plane
      vibrations, and >30 other overtones and combination bands. The B3LYP6-311++G(d,p)
      calculated anharmonic wave numbers are in very good agreement with the observed
      fundamentals, overtones, and combinations, with a deviation Delta(rms)=1.3%.

PMID- 16999476
TI  - Determination of chiral asymmetries in the valence photoionization of camphor
      enantiomers by photoelectron imaging using tunable circularly polarized light.
AB  - An electron imaging technique has been used to study the full angular
      distribution of valence photoelectrons produced from enantiomerically pure
      molecular beams of camphor when these are photoionized with circularly polarized
      light. In addition to the familiar beta parameter, this provides a new chiral
      term, taking the form of an additional cosine function in the angular
      distribution which consequently displays a forward-backward electron ejection
      asymmetry. Several ionization channels have been studied using synchrotron
      radiation in the 8.85-26 eV photon energy range. With alternating left and right
      circularly polarized radiations the photoelectron circular dichroism (PECD) in
      the angular distribution can be measured and shows some strong dynamical
      variations with the photon energy, depending in sign and intensity on the ionized
      orbital. For all orbitals the measured PECD has a quite perfect antisymmetry when
      switching between R and S enantiomers, as expected from theory. In the HOMO(-1)
      channel the PECD chiral asymmetry curves show a double maxima reaching nearly 10%
      close to threshold, and peaking again at approximately 20% some 11 eV above
      threshold. This is attributed to a resonance that is also visible in the beta
      parameter curve. Newly optimized CMS-Xalpha photoionization dynamics calculations
      are also presented. They are in reasonably good agreement with the experimental
      data, including in the very challenging threshold regions. These calculations
      show that PECD in such randomly oriented samples can be understood in the
      electric dipole approximation and that, unlike the case pertaining in core-shell
      ionization-where a highly localized achiral initial orbital means that the
      dichroism arises purely as a final state scattering effect-in valence shell
      ionization there is a significant additional influence contributed by the initial
      orbital density.

PMID- 16999477
TI  - Infrared spectra of isotopic CO2-He complexes.
AB  - Infrared spectra of three isotopic forms of the weakly bound CO(2)-He van der
      Waals complex have been studied in the region of the CO(2) nu(3) fundamental band
      around 2300 cm(-1), using a tunable diode laser to probe a pulsed supersonic
      expansion. The complex is a T-shaped near-oblate asymmetric rotor, and it is
      found that (18)O isotopic substitution is sufficient to interchange the a and b
      inertial axes. For the symmetric isotopes, such as the normal species and the
      (16)O(13)C(16)O and (18)O(13)C(18)O forms studied here, half of the normal
      rotational levels of the complex are missing due to the effects of (16)O (or
      (18)O) interchange symmetry. However, for asymmetrically substituted ones, such
      as (16)O(13)C(18)O, all rotational levels are present. Moreover, for the
      asymmetric isotope, both a- and b-type transitions were observed, so that the
      spectrum was much richer. The CO(2)-He system is of interest both as a benchmark
      for intermolecular potential energy surface calculations, and because CO(2) is a
      valuable probe molecule for helium cluster spectroscopy.

PMID- 16999478
TI  - On the semiclassical initial value calculation of thermal rate coefficients for
      the N+N2 reaction.
AB  - In this paper we compare semiclassical initial value representation, conventional
      transition state theory with Wigner and Eckart tunneling correction, quantum
      reduced dimensionality, and quasiclassical thermal rate coefficients for N+N(2)
      exchange reaction.

PMID- 16999479
TI  - CH radical production from 248 nm photolysis or discharge-jet dissociation of
      CHBr3 probed by cavity ring-down absorption spectroscopy.
AB  - The A-X bands of the CH radical, produced in a 248 nm two-photon photolysis or in
      a supersonic jet discharge of CHBr(3), have been observed via cavity ring-down
      absorption spectroscopy. Bromoform is a well-known photolytic source of CH
      radicals, though no quantitative measurement of the CH production efficiency has
      yet been reported. The aim of the present work is to quantify the CH production
      from both photolysis and discharge of CHBr(3). In the case of photolysis, the
      range of pressure and laser fluences was carefully chosen to avoid postphotolysis
      reactions with the highly reactive CH radical. The CH production efficiency at
      248 nm has been measured to be Phi=N(CH)N(CHBr(3))=(5.0+/-2.5)10(-4) for a
      photolysis laser fluence of 44 mJ cm(-2) per pulse corresponding to a two-photon
      process only. In addition, the internal energy distribution of CH(X (2)Pi) has
      been obtained, and thermalized population distributions have been simulated,
      leading to an average vibrational temperature T(vib)=1800+/-50 K and a rotational
      temperature T(rot)=300+/-20 K. An alternative technique for producing the CH
      radical has been tested using discharge-induced dissociation of CHBr(3) in a
      supersonic expansion. The CH product was analyzed using the same cavity ring-down
      spectroscopy setup. The production of CH by discharge appears to be as efficient
      as the photolysis technique and leads to rotationally relaxed radicals.

PMID- 16999480
TI  - Ab initio potential energy surface, infrared spectra, and dynamics of the ion
      molecule complexes between Br- and H2, D2, and HD.
AB  - A three-dimensional potential energy surface (PES) for the Br(-)-H(2) complex is
      computed using the ab initio CCSD(T) method and an extended basis set. The PES
      has two equivalent minima at the linear geometries (equilibrium interfragment
      distance R(e)=3.34 A and interaction energy D(e)=670 cm(-1)) separated by the
      barrier at the T-shaped configuration (interfragment distance R(e)=4.03 A and
      barrier height of 610 cm(-1)). Ab initio points are fitted to a flexible
      analytical form and used in the variational rovibrational energy level
      calculations. Simulated infrared spectra of the Br(-)-H(2) and Br(-)-D(2)
      complexes in the monomer stretching excitation region are in good agreement with
      the measured ones. Nonstatistical intensity ratios of the complexes of para- and
      ortho-monomers are qualitatively explained by monomer ligand exchange reactions.
      Predissociation of the complexes containing vibrationally excited monomers is
      analyzed and shown to proceed through the near-resonant vibration-to-rotation
      energy transfer. For complexes involving Br(-) and the HD monomer, two
      energetically low-lying states are predicted, corresponding predominately to the
      Br(-)-DH and Br(-)-HD isomeric forms. The results demonstrate the close
      similarity of the bromide containing complexes to their analogs containing the
      chloride anion.

PMID- 16999481
TI  - Radical SBr: a challenge to spectroscopists?
AB  - A theoretical description of the electronic states of the SBr radical at a high
      level of correlation effects treatment is presented for the first time. Most of
      its potential energy curves have a repulsive nature, but a set of bound (2)Pi
      states should provide a means for the experimental characterization of this
      species. The ground state can support over 40 vibrational states, but transitions
      from the 2 (2)Pi state, with a very shallow well (four levels), should have
      intensities spread over a maximum around v(")=10; lower vibrational levels can
      only be accessed for transitions from two high-lying Rydberg states. A whole set
      of spectroscopic constants, including vibrationally averaged spin-orbit coupling
      constants, and radiative transition probabilities and lifetimes quantify the
      theoretical description, thus supplying reliable results to guide the
      experimental investigation of this species.

PMID- 16999482
TI  - Theoretical spectroscopy of the calcium dimer in the A 1Sigma(u)+, c3Pi(u), and
      a3Sigma(u)+ manifolds: an ab initio nonadiabatic treatment.
AB  - Nonadiabatic theory of molecular spectra of diatomic molecules is presented. It
      is shown that in the fully nonadiabatic framework, the rovibrational wave
      functions describing the nuclear motions in diatomic molecules can be obtained
      from a system of coupled differential equations. The rovibrational wave functions
      corresponding to various electronic states are coupled through the relativistic
      spin-orbit coupling interaction and through different radial and angular coupling
      terms, while the transition intensities can be written in terms of the ground
      state rovibrational wave function and bound rovibrational wave functions of all
      excited electronic states that are electric dipole connected with the ground
      state. This theory was applied in the nearly exact nonadiabatic calculations of
      energy levels, line positions, and intensities of the calcium dimer in the A
      (1)Sigma(u) (+)(1 (1)S+1 (1)D), c (3)Pi(u)(1 (3)P+1 (1)S), and a (3)Sigma(u)
      (+)(1 (3)P+1 (1)S) manifolds of states. The excited state potentials were
      computed using a combination of the linear response theory within the coupled
      cluster singles and doubles framework for the core-core and core-valence
      electronic correlations and of the full configuration interaction for the valence
      valence correlation, and corrected for the one-electron relativistic terms
      resulting from the first-order many-electron Breit theory. The electric
      transition dipole moment governing the A (1)Sigma(u) (+)<--X (1)Sigma(g) (+)
      transitions was obtained as the first residue of the frequency-dependent
      polarization propagator computed with the coupled-cluster method restricted to
      single and double excitations, while the spin-orbit and nonadiabatic coupling
      matrix elements were computed with the multireference configuration interaction
      wave functions restricted to single and double excitations. Our theoretical
      results explain semiquantitatively all the features of the observed Ca(2)
      spectrum in the A (1)Sigma(u) (+)(1 (1)S+1 (1)D), c (3)Pi(u)(1 (3)P+1 (1)S), and
      a (3)Sigma(u) (+)(1 (3)P+1 (1)S) manifolds of states.

PMID- 16999483
TI  - A clue to the diffuse structure in ultraviolet spectra of the GeCl2 A-X
      transition.
AB  - Geometries, harmonic vibrational frequencies, and relative electronic energies of
      the two low-lying electronic states of the GeCl(2) dimer have been calculated at
      the CIS(D) method with a cc-pVTZ basis set. Minima corresponding to three isomers
      on the ground-state potential energy surface have been characterized. The most
      stable dimer has a dissociation energy of 0.74 eV and has a trans-(GeCl(2))(2)
      structure. There is also a related, less stable, cis minimum. A third, C(i)
      symmetry, isomer has a binding energy of 0.31 eV. It is found that this C(i)
      isomer has substantial dipole transition strength to the first excited singlet
      state of the dimer with a vertical excitation energy of 3.33 eV. The transition
      energy (T(0)) between this C(i) isomer and the van der Waals complex on the
      singlet excited state is predicted to be 4.007 eV, or a 1104 cm(-1) blueshift
      with respect to that of the GeCl(2) A-X transition. This finding may explain the
      diffuse structure which has been observed in the ultraviolet laser-induced
      fluorescence spectra of GeCl(2).

PMID- 16999484
TI  - The molecular origins of nonlinear response in solute energy relaxation: the
      example of high-energy rotational relaxation.
AB  - A key step in solution-phase chemical reactions is often the removal of excess
      internal energy from the product. Yet, the way one typically studies this process
      is to follow the relaxation of a solute that has been excited into some
      distribution of excited states quite different from that produced by any reaction
      of interest. That the effects of these different excitations can frequently be
      ignored is a consequence of the near universality of linear-response behavior,
      the idea that relaxation dynamics is determined by the solvent fluctuations
      (which may not be all that different for different kinds of solute excitation).
      Nonetheless, there are some clear examples of linear-response breakdowns seen in
      solute relaxation, including a recent theoretical and experimental study of
      rapidly rotating diatomics in liquids. In this paper we use this rotational
      relaxation example to carry out a theoretical exploration of the conditions that
      lead to linear-response failure. Some features common to all of the linear
      response breakdowns studied to date, including our example, are that the initial
      solute preparation is far from equilibrium, that the subsequent relaxation
      promotes a significant rearrangement of the liquid structure, and that the
      nonequilibrium response is nonstationary. However, we show that none of these
      phenomena is enough to guarantee a nonlinear response. One also needs a
      sufficient separation between the solute time scale and that of the solvent
      geometry evolution. We illustrate these points by demonstrating precisely how our
      relaxation rate is tied to our liquid-structural evolution, how we can
      quantitatively account for the initial nonstationarity of our effective
      rotational friction, and how one can tune our rotational relaxation into and out
      of linear response.

PMID- 16999485
TI  - Depolarized light scattering versus optical Kerr effect spectroscopy of
      supercooled liquids: comparative analysis.
AB  - Recently, heterodyne-detected optical Kerr effect (HD-OKE) spectroscopy was used
      to study dynamics of supercooled molecular liquids. The studies revealed an
      apparently new physical phenomenon that had not been reported before from the
      related depolarized light scattering (DLS), namely, an intermediate power law
      (nearly logarithmic decay) of the response functions [H. Cang et al., J. Chem.
      Phys. 118, 2800 (2003)]. Conceptually, HD-OKE and DLS data reflect optical
      anisotropy fluctuations mainly due to molecular reorientation dynamics in time
      and frequency domains, respectively. The above-mentioned effects are revealed in
      the mesoscopic range less, similar1 GHz ( greater, similar100 ps), where no
      direct comparison of the techniques was reported. In this Communication, we
      attempt such a comparison of exemplifying HD-OKE literature data of the glass
      forming salol (phenyl salicylate), benzophenone, and liquid-crystal forming 4
      cyano-4(')-pentylbiphenyl with DLS data of the same systems that we measured down
      to ca. 200 MHz by a combined tandem Fabry-Perot interferometer plus tandem
      grating-monochromator technique. Generally, we find a satisfactory agreement,
      albeit in some cases with subtle differences at frequencies greater, similar10
      GHz. We conclude that, in the mesoscopic dynamic range, HD-OKE and DLS studies
      provide consistent and comparable information, and therefore their conclusions
      must agree. We argue that the intermediate power law of HD-OKE is in essence a
      manifestation of the excess wing of the corresponding frequency-domain data,
      known long since from broadband dielectric spectroscopy and anticipated from DLS
      studies of supercooled liquids.

PMID- 16999486
TI  - Determination of the nonlinear dielectric increment in the Cole-Davidson model.
AB  - The problem of the nonlinear dielectric relaxation of complex liquids is tackled
      in the context of the Cole-Davidson [J. Chem. Phys. 19, 1484 (1951)] model. By
      using an appropriate time derivative of noninteger order, an infinite hierarchy
      of differential-recurrence relations for the moments (expectation values of the
      Legendre polynomials) is obtained. The solution is established for the stationary
      regime of an ensemble of polar and symmetric-top molecules acted on by a strong
      dc bias electric field superimposed on a weak ac electric field. The results for
      the first three nonlinear harmonic components of the electric susceptibility are
      analytically established and illustrated with the help of Argand diagrams for the
      nonlinear dielectric increment and three-dimensional dispersion and absorption
      spectra for the second and the third harmonic components as a function of the
      anomalous exponent beta</=1, the value of which gives rise to skewed arcs (Argand
      plots) and asymmetric shapes (loss spectra) in the high-frequency domain.

PMID- 16999487
TI  - Size distribution of nuclei in a closed system.
AB  - Kinetic equations describing the formation of nuclei from a supersaturated vapor
      in a closed system are solved numerically to determine the size distribution of
      nuclei at various times. Depletion of vapor phase during phase transition process
      is taken into account. Evolution of the size distribution of nuclei is analyzed.
      Due to the decrease of the supersaturation of the vapor phase, a maximum appears
      in the size distribution of nuclei, which disappears at sufficiently long time.
      Supersaturation of the mother phase decreases to a value close to 1.

PMID- 16999488
TI  - Structure and phase behavior of Widom-Rowlinson model calculated from a
      nonuniform Ornstein-Zernike equation.
AB  - The second-order integral-equation formalism of [Attard J. Chem. Phys. 91, 3072
      (1989); 95, 4471 (1991)], applied previously to one-component hard spheres and
      Lennard-Jones fluids, as well as to their mixtures, is used to binary Widom
      Rowlinson mixtures. Comparison with Monte Carlo simulations of the pair
      correlation functions and of the demixing phase diagram shows that this method is
      also quite accurate in the case of highly nonadditive mixtures. Moreover, the
      results of the second-order theory are compared with previous theoretical
      predictions. Our interest is also in the calculation of the bridge functions,
      i.e., parts of the radial distribution functions either not included or simply
      approximated in the usual theories.

PMID- 16999489
TI  - Controlling and characterizing the coagulation of liquid aerosol droplets.
AB  - We demonstrate that optical tweezers can be used to control and characterize the
      coagulation and mixing state of aerosols. Liquid aerosol droplets of 2-14 mum in
      diameter are optically trapped and characterized by spontaneous and stimulated
      Raman scatterings, which together provide a unique signature of droplet size and
      composition. From the conventional bright field image, the size of the trapped
      droplet can be estimated and compared with that determined from stimulated Raman
      scattering, and the motion of the particle within the trapping plane can be
      recorded. A maximum of four droplets can be manipulated in tandem by forming
      multiple optical traps through rapid beam steering. The coagulation of two
      droplets can be studied directly by controlling two droplets. The limiting
      conditions under which optical forces and capillary forces dominate the aerosol
      coagulation event are explored by varying the relative optical trap strengths and
      characterizing the coagulation of different droplet sizes. Finally, we
      demonstrate that the coagulation of different aerosol components can be compared
      and the mixing state of the final coagulated droplet can be investigated. In
      particular, we compare the outcome of the coagulation of an aqueous sodium
      chloride aerosol droplet with a second aqueous droplet, with an ethanol droplet
      or with a decane droplet.

PMID- 16999490
TI  - Volumes of critical bubbles from the nucleation theorem.
AB  - A corollary of the nucleation theorem due to Kashchiev [Nucleation: Basic Theory
      with Applications (Butterworth-Heinemann, Oxford, 2000)] allows the volume V(*)
      of a critical bubble to be determined from nucleation rate measurements. The
      original derivation was limited to one-component, ideal gas bubbles with a vapor
      density much smaller than that of the ambient liquid. Here, an exact result is
      found for multicomponent, nonideal gas bubbles. Provided a weak density
      inequality holds, this result reduces to Kashchiev's simple form which thus has a
      much broader range of applicability than originally expected. Limited
      applications to droplets are also mentioned, and the utility of the p(T,x) form
      of the nucleation theorem as a sum rule is noted.

PMID- 16999491
TI  - Vibrational dynamics of DNA. I. Vibrational basis modes and couplings.
AB  - Carrying out density functional theory calculations of four DNA bases, base
      derivatives, Watson-Crick (WC) base pairs, and multiple-layer base pair stacks,
      we studied vibrational dynamics of delocalized modes with frequency ranging from
      1400 to 1800 cm(-1). These modes have been found to be highly sensitive to
      structure fluctuation and base pair conformation of DNA. By identifying eight
      fundamental basis modes, it is shown that the normal modes of base pairs and
      multilayer base pair stacks can be described by linear combinations of these
      vibrational basis modes. By using the Hessian matrix reconstruction method,
      vibrational coupling constants between the basis modes are determined for WC base
      pairs and multilayer systems and are found to be most strongly affected by the
      hydrogen bonding interaction between bases. It is also found that the propeller
      twist and buckle motions do not strongly affect vibrational couplings and basis
      mode frequencies. Numerically simulated IR spectra of guanine-cytosine and
      adenine-thymine bases pairs as well as of multilayer base pair stacks are
      presented and described in terms of coupled basis modes. It turns out that, due
      to the small interlayer base-base vibrational interactions, the IR absorption
      spectrum of multilayer base pair system does not strongly depend on the number of
      base pairs.

PMID- 16999492
TI  - Vibrational dynamics of DNA. II. Deuterium exchange effects and simulated IR
      absorption spectra.
AB  - In Paper I, we studied vibrational properties of normal bases, base derivatives,
      Watson-Crick base pairs, and multiple layer base pair stacks in the frequency
      range of 1400-1800 cm(-1). However, typical IR absorption spectra of single- and
      double-stranded DNA have been measured in D(2)O solution. Consequently, the more
      relevant bases and base pairs are those with deuterium atoms in replacement with
      labile amino hydrogen atoms. Thus, we have carried out density functional theory
      vibrational analyses of properly deuterated bases, base pairs, and stacked base
      pair systems. In the frequency range of interest, both aromatic ring deformation
      modes and carbonyl stretching modes appear to be strongly IR active. Basis mode
      frequencies and vibrational coupling constants are newly determined and used to
      numerically simulate IR absorption spectra. It turns out that the hydration
      effects on vibrational spectra are important. The numerically simulated
      vibrational spectra are directly compared with experiments. Also, the (18)O
      isotope exchange effect on the poly(dG):poly(dC) spectrum is quantitatively
      described. The present calculation results will be used to further simulate two
      dimensional IR photon echo spectra of DNA oligomers in the companion Paper III.

PMID- 16999493
TI  - Vibrational dynamics of DNA. III. Molecular dynamics simulations of DNA in water
      and theoretical calculations of the two-dimensional vibrational spectra.
AB  - A theoretical description of the vibrational excitons in DNA is presented by
      using the vibrational basis mode theory developed in Papers I and II. The
      parameters obtained from the density functional theory calculations, such as
      vibrational coupling constants and basis mode frequencies, are used to
      numerically simulate two-dimensional (2D) IR spectra of dG(n):dC(n) and
      dA(n):dT(n) double helices with n varying from 1 to 10. From the molecular
      dynamics simulations of dG(5)C(5) and dA(5)T(5) double helices in D(2)O solution,
      it is found that the thermally driven internal motions of these systems in an
      aqueous solution do not induce strong fluctuations of basis mode frequencies nor
      vibrational couplings. In order to construct the two-exciton Hamiltonian, the
      vibrational anharmonicities of eight basis modes are obtained by carrying out
      B3LYP6-31G(*) calculations for the nine basis modes. The simulated 2D IR spectra
      of dG(n):dC(n) double helix in D(2)O solution are directly compared with closely
      related experimental results. The 2D IR spectra of dG(n):dC(n) and dA(n):dT(n)
      are found to be weakly dependent on the number of base pairs. The present work
      demonstrates that the computational procedure combining quantum chemistry
      calculation and molecular dynamics simulation methods can be of use to predict 2D
      IR spectra of nucleic acids in solutions.

PMID- 16999495
TI  - Effect of quantum partial charges on the structure and dynamics of water in
      single-walled carbon nanotubes.
AB  - In this work, using quantum partial charges, computed from 6-31G(**)B3LYP density
      functional theory, in molecular dynamics simulations, we found that water inside
      (6,6) and (10,0) single-walled carbon nanotubes with similar diameters but with
      different chiralities has remarkably different structural and dynamical
      properties. Density functional calculations indicate that tubes with different
      chiralities have significantly different partial charges at the ends of tubes.
      The partial charges at the ends of a (10,0) tube are around 4.5 times higher than
      those of a (6,6) tube. Molecular dynamics simulations with the partial charges
      show different water dipole orientations. In the (10,0) tube, dipole vectors of
      water molecules at the end of the tube point towards the water reservoir
      resulting in the formation of an L defect in the center region. This is not
      observed in the (6,6) tube where dipole vectors of all the water molecules inside
      the tube point towards either the top or the bottom water reservoir. The water
      diffusion coefficient is found to increase in the presence of the partial
      charges. Water in the partially charged (10,0) tube has a lower diffusion
      coefficient compared to that of in the partially charged (6,6) tube.

PMID- 16999494
TI  - Molecular dynamics simulation of glycine zwitterion in aqueous solution.
AB  - A classical molecular dynamics method was used to study the modifications of the
      solution structure and the properties of glycine zwitterion in aqueous solution
      due to the increase of glycine zwitterion concentration and the incorporation of
      Na(+) and Cl(-) ions to the solution. The glycine zwitterion had fundamentally a
      hydrophilic behavior at infinite dilution, establishing around six hydrogen bonds
      with the water molecules that surrounded it, which formed a strong hydration
      layer. Because of the increase of glycine zwitterion concentration, the hydration
      structure became more compact and the quantity of water molecules bound to this
      molecule decreased. The Na(+) ion bound to the CO(2) group of glycine, while the
      Cl(-) ion bound mainly to the NH(3) group of this molecule. The integration of
      the ions to the hydration layer of the glycine zwitterion produced modifications
      in the orientational correlation between atoms of glycine zwitterion and water
      that surrounded them and an increase of the approaches between the glycine
      zwitterion molecules. The incorporation of ions to the solution also produced
      changes in the water-water orientational correlation. Decreases of the water
      water hydrogen bonds and diffusion coefficient of all molecules were observed
      when the glycine zwitterion concentration increased and when the ions were
      incorporated to the solution.

PMID- 16999496
TI  - Structure, dynamics, and electronic properties of lithium disilicate melt and
      glass.
AB  - Ab initio molecular dynamics simulations within the framework of density
      functional theory have been performed to study the structural, dynamic, and
      electronic properties of lithium disilicate melt and the glass derived from
      quenching the melt. It is found that lithium ions have a much higher diffusion
      coefficient and show different diffusion mechanisms than the network forming
      silicon and oxygen ions in the melt. The simulated lithium disilicate glass
      structure has 100% four coordinated silicon, close to theoretical nonbridging
      oxygen to bridging oxygen ratio (2:3), and Q(n) distributions of 20.8%, 58.4%,
      and 20.8% for n=2,3,4, respectively. In the melt there are considerable amounts
      (10%-15%) of silicon coordination defects; however, the average silicon
      coordination number remains about 4, similar to that in the glass. The lithium
      ion coordination number increases from 3.7 in the glass to 4.4 in the melt mainly
      due to the increase of bridging oxygen in the first coordination shell. The bond
      length and bond angle distributions, vibrational density of states, and static
      structure factors of the simulated glass were determined where the latter was
      found to be in good agreement with experimental measurement. Atomic charges were
      obtained based on Bader and Hirshfeld population analyses [Atoms in Molecule: A
      Quantum Theory (Oxford University Press, Oxford, 1990); Theor. Chim. Acta 44, 129
      (1977)]. The average Bader charges found in lithium disilicate glass were -1.729,
      3.419, and 0.915 for oxygen, silicon, and lithium, respectively. The
      corresponding Hirshfeld charges were -0.307, 0.550, and 0.229. The electronic
      densities of states of the melt and glass were calculated and compared with those
      of crystalline lithium disilicate.

PMID- 16999497
TI  - Topological characterization of crystallization of gold nanoclusters.
AB  - In this study we use a new topological structure measure to analyze the local
      environment of 923 atom gold clusters quenched from the melt, at various quench
      rates, by molecular dynamics. The crystallization and geometrical rearrangements
      of the core atoms upon freezing can be clearly observed using our structure
      measure which is based on planar graphs. Our results support the hypothesis that
      crystallization is initiated from the surface and proceeds into the cluster core.

PMID- 16999498
TI  - First-principles electronic transport calculations in finite elongated systems: a
      divide and conquer approach.
AB  - We present a first-principles method for the evaluation of the transmittance
      probability and the coherent conductance through elongated systems composed of a
      repeating molecular unit and terminated at both ends. Our method is based on a
      divide and conquer approach in which the Hamiltonian of the elongated system can
      be represented by a block tridiagonal matrix, and therefore can be readily
      inverted. This allows us to evaluate the transmittance and the conductance using
      first-principles electronic structure methods without explicitly performing
      calculations involving the entire system. A proof of concept model based on a
      trans-polyacetylene chain bridging two aluminum leads indicates that our divide
      and conquer approach is able to capture all the features appearing in the
      transmittance probability curves obtained by a full scale calculation.

PMID- 16999499
TI  - Photoinduced fluorescence intensity oscillation in a reaction-diffusion cell
      containing a colloidal quantum dot dispersion.
AB  - The nonlinear spontaneous oscillation of photoluminescence (PL) intensity in an
      ensemble of semiconductor quantum dots (QDs), which differs from the fluorescence
      intermittency of a single QD, is investigated. The PL intensity in a QD
      dispersion slowly oscillates with time under continuous illumination. The
      oscillatory behavior is found to vary with changing QD concentration, solvent
      viscosity, volume fraction of irradiated region, and irradiation intensity. On
      the basis of the Gray-Scott model [Chemical Oscillation and Instabilities: Non
      linear Chemical Kinetics (Clarendon, Oxford, 1994); J. Phys. Chem. 89, 22 (1985);
      Chem. Eng. Sci. 42, 307 (1987)], and its comparison with the experimental
      results, it is revealed that the following processes are important for PL
      oscillation: (1) mass transfer of QDs between the illuminated and dark regions,
      (2) autocatalytic formation of vacant sites on QD surfaces via photodesorption of
      ligand molecules, and (3) passivation of vacant sites via photoadsorption of
      water molecules.

PMID- 16999500
TI  - Reactive and nonreactive scattering of N2 from Ru(0001): a six-dimensional
      adiabatic study.
AB  - We have studied the dissociative chemisorption and scattering of N(2) on and from
      Ru(0001), using a six-dimensional quasiclassical trajectory method. The potential
      energy surface, which depends on all the molecular degrees of freedom, has been
      built applying a modified Shepard interpolation method to a data set of results
      from density functional theory, employing the RPBE generalized gradient
      approximation. The frozen surface and Born-Oppenheimer [Ann. Phys. (Leipzig) 84,
      457 (1927)] approximations were used, neglecting phonons and electron-hole pair
      excitations. Dissociative chemisorption probabilities are found to be very small
      even for translational energies much higher than the minimum reaction barrier, in
      good agreement with experiment. A comparison to previous low dimensional
      calculations shows the importance of taking into account the multidimensional
      effects of N(2) rotation and translation parallel to the surface. The new
      calculations strongly suggest a much smaller role of nonadiabatic effects than
      previously assumed on the basis of a comparison between low dimensional results
      and experiments [J. Chem. Phys. 115, 9028 (2001)]. Also in agreement with
      experiment, our theoretical results show a strong dependence of reaction on the
      initial vibrational state. Computed angular scattering distributions and parallel
      translation energy distributions are in good agreement with experiments on
      scattering, but the theory overestimates vibrational and rotational excitations
      in scattering.

PMID- 16999501
TI  - Water as a lubricant for graphite: a computer simulation study.
AB  - The phase state and shear behavior of water confined between parallel graphite
      sheets are studied using the grand canonical Monte Carlo technique and TIP4P
      model for water. In describing the water-graphite interaction, two orientation
      dependent potentials are tried. Both potentials are fitted to many-body
      polarizable model predictions for the binding energy and the equilibrium
      conformation of the water-graphite complex [K. Karapetian and K. D. Jordan in
      Water in Confining Geometries, edited by V. Buch and J. P. Devlin (Springer,
      Berlin, 2003), pp. 139-150]. Based on the simulation results, the property of
      water to serve as a lubricant between the rubbing surfaces of graphitic particles
      is associated, first, with the capillary condensation of water occurring in
      graphitic pores of monolayer width and, second, with the fact that the water
      monolayer compressed between graphite particles retains a liquidlike structure
      and offers only slight resistance to shear.

PMID- 16999502
TI  - Xe nuclear magnetic resonance line shapes in channels decorated with paramagnetic
      centers.
AB  - To make predictions of the Xe NMR line shapes for Xe in channels decorated with
      paramagnetic centers, we consider a model system using the O(2) molecule as the
      paramagnetic center. The previously calculated quantum mechanical Xe@O(2)
      hyperfine tensor for various configurations of Xe in the presence of O(2)
      provides a model for the hyperfine response of Xe atom to the presence of a
      paramagnetic center. The averaging is carried out using the same grand canonical
      Monte Carlo methodology as for calculating NMR line shapes for Xe in diamagnetic
      channels, modified to include the effects of the hyperfine tensor response. We
      explore the temperature dependence of the Xe line shapes, the dependence on the
      concentration, and the symmetry of distribution of embedded paramagnetic centers,
      on the orientation of the paramagnetic center axis with respect to the channel
      axis, and on the radial distance of the paramagnetic center from the axis of the
      channel. We predict Xe line shape signatures of the presence and orientation of
      paramagnetic centers and deduce which tensor elements provide measures of
      concentration and radial distance of paramagnetic centers from the channel axis.

PMID- 16999503
TI  - Adsorbate coverages and surface reactivity in methanol oxidation over Cu(110): An
      in situ photoelectron spectroscopy study.
AB  - The adsorbate species present during partial oxidation of methanol on a Cu(110)
      surface have been investigated in the 10(-5) mbar range with in situ x-ray
      photoelectron spectroscopy and rate measurements. Two reaction intermediates were
      identified, methoxy with a C 1s binding energy (BE) of 285.4 eV and formate with
      a C 1s BE of 287.7 eV. The c(2x2) overlayer formed under reaction conditions is
      assigned to formate. Two states of adsorbed oxygen were found characterized by O
      1s BE's of 529.6 and 528.9 eV, respectively. On the inactive surface present at
      low T around 300-350 K formate dominates while methoxy is almost absent. Ignition
      of the reaction correlates with a decreasing formate coverage. A large hysteresis
      of approximately 200 K occurs in T-cycling experiments whose correlation with
      adsorbate species was studied with varying oxygen and methanol partial pressures.
      The two branches of the hysteresis differ mainly in the amount of adsorbed
      oxygen, the methoxy species, and a carbonaceous species. Methoxy covers only a
      minor part of the catalytic surface reaching at most 20%. Above 650 K the surface
      is largely adsorbate-free.

PMID- 16999504
TI  - Two-component membrane material properties and domain formation from dissipative
      particle dynamics.
AB  - The material parameters (area stretch modulus and bending rigidity) of two
      component amphiphilic membranes are determined from dissipative particle dynamics
      simulations. The preferred area per molecule for each species is varied so as to
      produce homogeneous mixtures or nonhomogeneous mixtures that form domains. If the
      latter mixtures are composed of amphiphiles with the same tail length, but
      different preferred areas per molecule, their material parameters increase
      monotonically as a function of composition. By contrast, mixtures of amphiphiles
      that differ in both tail length and preferred area per molecule form both
      homogeneous and nonhomogeneous mixtures that both exhibit smaller values of their
      material properties compared to the corresponding pure systems. When the same
      nonhomogeneous mixtures of amphiphiles are assembled into planar membrane patches
      and vesicles, the resulting domain shapes are different when the bending
      rigidities of the domains are sufficiently different. Additionally, both bilayer
      and monolayer domains are observed in vesicles. We conclude that the evolution of
      the domain shapes is influenced by the high curvature of the vesicles in the
      simulation, a result that may be relevant for biological vesicle membranes.

PMID- 16999505
TI  - Direct simulations of flexible cylindrical fiber suspensions in finite Reynolds
      number flows.
AB  - Direct simulations of flexible cylindrical fiber suspensions in a finite Reynolds
      number flow are reported. The simulation method is based on a lattice Boltzmann
      equation and a flexible fiber model. A slender solid body is discretized into a
      chain of cylindrical segments contacting each other at the their ends through
      ball and socket joints that allow adjacent segments to rotate around the joints
      in three dimensional space. A constraint force is imposed at each joint. In
      general, motion and rotational matrices of each segment are functions of
      constraint forces. It is necessary to linearize the rotational matrices in forces
      and torques so that constraint forces could be solved using joint contacting
      conditions. Therefore, quaternion parameters as well as rotational matrix could
      be expanded in a power series of the length of time step up to a second order. A
      half leapfrog algorithm D. Fincham, [CCP5 Quarterly, 2, 6 (1981)] is modified to
      ensure the ball and socket joint conditions to be satisfied at each time step.
      The validation of the present flexible fiber method is tested by using a rigid
      particle method. It is shown that the computational results are consistent with
      the existing experimental and theoretical results at finite Reynolds number
      flows. With the present method, nonlinear inertial interactions between fluid and
      flexible filaments can be naturally studied. A few applications are included.

PMID- 16999506
TI  - A comparative study of the properties of polar and nonpolar
      solvent/solute/polystyrene solutions in microwave fields via molecular dynamics.
AB  - The influence of an applied microwave field on the dynamics of methylamine
      dichloromethane (DCM) mixtures bound within atactic polystyrene (a-PS) over a
      range of polymer densities from 30 to 94 wt % polymer was examined using
      atomistic molecular dynamics simulations. This study is an extension of previous
      studies on methylamine transport in relatively polar polystyrene solutions of
      methanol and dimethylformamide [M. J. Purdue et al., J. Chem. Phys. 124, 204904
      (2006)]. A direct comparison is made across the three types of polystyrene
      solutions. Consideration is given to both solvent and reagent transport within
      the polymer solutions under zero-field conditions and in an external
      electromagnetic field in the canonical ensemble (NVT) at 298.0 K. Various
      frequencies up to 10(4) GHz and a rms electric field intensity of 0.1 VA were
      applied. The simulation studies were validated by comparison of the simulated
      zero-field self-diffusion coefficients of DCM in a-PS with those obtained using
      pulsed-gradient spin-echo NMR spectrometry. Athermal effects of microwave fields
      on solute transport behavior within polymer solutions are discussed.

PMID- 16999507
TI  - Computer simulation of two new solid phases of water: Ice XIII and ice XIV.
AB  - NpT Monte Carlo simulations have been performed for two recently discovered solid
      phases of water which have been denoted as ice XIII and ice XIV C. G. Salzmann et
      al. [Science311, 1758 (2006)]. Several potential models of water were considered,
      namely, the traditional SPC/E, TIP4P, and TIP5P and the more recent TIP5P-E,
      TIP4P-Ew, TIP4P/Ice, and TIP4P/2005 models. Significant differences in density
      and oxygen-oxygen radial distribution functions are found between the predictions
      of the SPC/E, TIP5P, and the models of the TIP4P family. The models TIP4P/Ice and
      TIP4P/2005 provide the best estimates of the density.

PMID- 16999509
TI  - Relaxed core projector-augmented-wave method.
AB  - We extend the full-potential projector-augmented-wave method beyond the frozen
      core approximation, i.e., include the self-consistent optimization of the core
      charge density, in such a manner that the valence wave functions remain
      orthogonal to the core. The method consists of an on-the-fly repseudization of
      the all-electron problem, solving for the self-consistent core charge density
      within a spherical approximation. The key ideas in our procedure are to keep the
      projector functions fixed throughout the electronic minimization and to derive
      the new pseudopartial waves from these original projector functions, at each step
      of the electronic minimization procedure. Results of relaxed core calculations
      for atomic interconfigurational energies, structural energy differences between
      bulk phases of Fe, atomization energies of a subset of Pople's G2-1 set, and the
      Rh 3d surface core level shifts for the (log3 x log3)-Rh(111) surface at 1/3 CO
      coverage are presented.

PMID- 16999510
TI  - Orbital disproportionation and spin crossover as a pseudo Jahn-Teller effect.
AB  - It is shown that in systems with electronic half-closed-shell configurations of
      degenerate orbitals, e(2) and t(3) (which have totally symmetric charge
      distribution), ground state distortions from high-symmetry geometries may occur
      due to a strong pseudo Jahn-Teller effect (PJTE) in the excited states, resulting
      also in a novel phenomenon of PJT-induced spin crossover. There is no JTE neither
      in the ground state term nor in the excited terms (including degenerate terms) of
      these configurations but a strong PJT mixing between two excited states
      [((1)E+(1)A) [cross-filled circle] e and ((2)T(1)+(2)T(2)) [cross-filled circle]
      e in the e(2) and t(3) cases, respectively] pushes down the lower term to cross
      the ground state of the undistorted system and to form the global minimum with a
      distorted geometry. The analysis of the electronic structure of this distorted
      configuration shows that it is accompanied by orbital disproportionation: instead
      of proportional population of all degenerate orbitals by one electron each (as in
      the ground state of the undistorted system that follows Hund's rule), two
      electrons with opposite spins occupy one orbital, resulting in transformations of
      the type (e(theta);e(epsilon))-->(e(theta)e(theta)) for e(2) and (t(x);t(y);t(z))
      ->(t(x);t(x);t(z)) for t(3) systems. Since the two geometry configurations,
      undistorted and distorted, appertain to different electronic terms that have
      different spin states, the formation of the global minimum with the distorted
      configuration is accompanied by a spin crossover. Distinguished from the known
      spin-crossover phenomenon in some transition metal compounds, the two states with
      different spin in the PJT-induced spin crossover have also different nuclear
      configurations, undistorted and distorted, that coexist with a relatively small
      energy difference. The change of configuration reduces significantly the rate of
      relaxation between the two states; the relaxation is further reduced by the lower
      spin-orbital coupling in the light-atom systems as compared with transition metal
      compounds. This means that there may be systems for which the switch between the
      two states (in both directions) under perturbations may be observed as a single
      molecule phenomenon. Systems with half-closed-shell electronic configurations
      e(2) and t(3) are available in a variety of molecules from different classes,
      organic and inorganic; the theory is illustrated here by ab initio calculations
      for a series of molecular systems, including Si(3), Si(3)C, CuF(3), Na(3), Si(4),
      Na(4), Na(4) (-), and C(60) (3-), which are in agreement with the experimental
      data available.

PMID- 16999511
TI  - Efficient evaluation of short-range Hartree-Fock exchange in large molecules and
      periodic systems.
AB  - We present an efficient algorithm for the evaluation of short-range Hartree-Fock
      exchange energies and geometry gradients in Gaussian basis sets. Our method uses
      a hierarchy of screening levels to eliminate negligible two-electron integrals
      whose evaluation is the fundamental computational bottleneck of the procedure. By
      applying our screening technique to the Heyd-Scuseria-Ernzerhof [J. Chem. Phys.
      118, 8207 (2003)] short-range Coulomb hybrid density functional, we achieve a
      computational efficiency comparable with that of standard nonhybrid density
      functional calculations.

PMID- 16999512
TI  - Accuracy and efficiency of electronic energies from systematic molecular
      fragmentation.
AB  - A systematic method for approximating the ab initio electronic energy of
      molecules from the energies of molecular fragments is tested on a large sample of
      typical organic molecular structures. The detailed methods, including some
      additional refinements for molecular rings and long range interactions, are
      described. The accuracy and computational efficiency of the systematic hierarchy
      of methods are reported.

PMID- 16999513
TI  - Interpolation of multidimensional diabatic potential energy matrices.
AB  - A method for constructing diabatic potential energy matrices by interpolation of
      ab initio quantum chemistry data is described and tested. This approach is
      applicable to any number of interacting electronic states, and relies on a
      formalism and a computational procedure that are more general than those
      presented previously for the case of two electronic states. The method is tested
      against an analytic model for three interacting electronic states of NH(3) (+).

PMID- 16999514
TI  - Local CC2 electronic excitation energies for large molecules with density
      fitting.
AB  - A new local method for the computation of electronic excitation energies of
      singlet states in extended molecular systems is presented. It is based on the CC2
      model and local approximations to the wave functions. In the proposed method the
      singles excitations are treated nonlocally and local restrictions are imposed on
      doubles amplitudes only. The accuracy of the new method was tested by calculating
      several lowest excited states for 14 molecules and comparing them with canonical
      CC2 values. Deviations of the local excitation energies from the canonical
      reference values do not exceed 0.05 eV for all test molecules and all states in
      the lower energy range investigated in this work. The method uses the density
      fitting approximation for all two-electron integrals, which considerably
      simplifies the computational complexity of the individual diagrams. A combination
      of the local approximations and the powerful density-fitting technique leads to a
      low-scaling method, capable to treat molecular systems comprised of 100 atoms and
      more in a basis of a polarized double zeta quality. A test calculation for a
      system consisting of 127 atoms and 370 active electrons without symmetry is
      presented to show the efficiency of the new method.

PMID- 16999515
TI  - LANL2DZ basis sets recontracted in the framework of density functional theory.
AB  - In this paper we report recontracted LANL2DZ basis sets for first-row transition
      metals. The valence-electron shell basis functions were recontracted using the
      PWP86 generalized gradient approximation functional and the hybrid B3LYP one.
      Starting from the original LANL2DZ basis sets a cyclic method was used in order
      to optimize variationally the contraction coefficients, while the contraction
      scheme was held fixed at the original one of the LANL2DZ basis functions. The
      performance of the recontracted basis sets was analyzed by direct comparison
      between calculated and experimental excitation and ionization energies. Results
      reported here compared with those obtained using the original basis sets show
      clearly an improvement in the reproduction of the corresponding experimental
      gaps.

PMID- 16999516
TI  - Ab initio correlation functionals from second-order perturbation theory.
AB  - Orbital-dependent exchange-correlation functionals are not limited by the
      explicit dependence on the density and present an attractive alternative to
      conventional functionals. With the successful implementation of the exact orbital
      dependent exchange functional, the challenge lies in developing orbital-dependent
      approximations for the correlation functional. Ab initio many-body methods can
      provide such approximations. In particular, perturbation theory with the Kohn
      Sham model as the reference [Gorling and Levy, Phys. Rev. A 50, 196 (1994)]
      defines the exact correlation functional via an infinite perturbation series. The
      second-order term of these series gives the lowest-order approximation to the
      correlation functional. However, it has been suggested [Bartlett et al., J. Chem.
      Phys. 122, 034104 (2005)] that the Kohn-Sham Hamiltonian is not the optimal
      choice for the perturbation expansion and a different reference Hamiltonian may
      lead to an improved perturbation series and more accurate second-order
      approximation. Here, we demonstrate explicitly that the modified series can be
      used to define superior functional and potential. We present results of atomic
      and molecular calculations with both second-order functionals. Our results
      demonstrate that the modified functional offers a significantly improved
      description of the correlation effects as it does not suffer from convergence
      problems and results in energies and densities that are more accurate than those
      obtained with second-order Moller-Plesset perturbation theory or generalized
      gradient approximation functionals.

PMID- 16999517
TI  - Molecular tailoring approach for geometry optimization of large molecules: energy
      evaluation and parallelization strategies.
AB  - A linear-scaling scheme for estimating the electronic energy, gradients, and
      Hessian of a large molecule at ab initio level of theory based on fragment set
      cardinality is presented. With this proposition, a general, cardinality-guided
      molecular tailoring approach (CG-MTA) for ab initio geometry optimization of
      large molecules is implemented. The method employs energy gradients extracted
      from fragment wave functions, enabling computations otherwise impractical on PC
      hardware. Further, the method is readily amenable to large scale coarse-grain
      parallelization with minimal communication among nodes, resulting in a near
      linear speedup. CG-MTA is applied for density-functional-theory-based geometry
      optimization of a variety of molecules including alpha-tocopherol, taxol, gamma
      cyclodextrin, and two conformations of polyglycine. In the tests performed,
      energy and gradient estimates obtained from CG-MTA during optimization runs show
      an excellent agreement with those obtained from actual computation. Accuracy of
      the Hessian obtained employing CG-MTA provides good hope for the application of
      Hessian-based geometry optimization to large molecules.

PMID- 16999518
TI  - Parallel algorithm for the computation of the Hartree-Fock exchange matrix: gas
      phase and periodic parallel ONX.
AB  - In this paper we present an efficient parallelization of the ONX algorithm for
      linear computation of the Hartree-Fock exchange matrix [J. Chem. Phys. 106, 9708
      (1997)]. The method used is based on the equal time (ET) partitioning recently
      introduced [J. Chem. Phys. 118, 9128 (2003)] and [J. Chem. Phys. 121, 6608
      (2004)]. ET exploits the slow variation of the density matrix between self
      consistent-field iterations to achieve load balance. The method is presented and
      some benchmark calculations are discussed for gas phase and periodic systems with
      up to 128 processors. The current parallel ONX code is able to deliver up to 77%
      overall efficiency for a cluster of 50 water molecules on 128 processors (2.56
      processors per heavy atom) and up to 87% for a box of 64 water molecules (two
      processors per heavy atom) with periodic boundary conditions.

PMID- 16999519
TI  - The correlation-consistent composite approach: application to the G3/99 test set.
AB  - The correlation-consistent composite approach (ccCA), an ab initio composite
      technique for computing atomic and molecular energies, recently has been shown to
      successfully reproduce experimental data for a number of systems. The ccCA is
      applied to the G3/99 test set, which includes 223 enthalpies of formation, 88
      adiabatic ionization potentials, 58 adiabatic electron affinities, and 8
      adiabatic proton affinities. Improvements on the original ccCA formalism include
      replacing the small basis set quadratic configuration interaction computation
      with a coupled cluster computation, employing a correction for scalar
      relativistic effects, utilizing the tight-d forms of the second-row correlation
      consistent basis sets, and revisiting the basis set chosen for geometry
      optimization. With two types of complete basis set extrapolation of MP2 energies,
      ccCA results in an almost zero mean deviation for the G3/99 set (with a best
      value of -0.10 kcal mol(-1)), and a 0.96 kcal mol(-1) mean absolute deviation,
      which is equivalent to the accuracy of the G3X model chemistry. There are no
      optimized or empirical parameters included in the computation of ccCA energies.
      Except for a few systems to be discussed, ccCA performs as well as or better than
      Gn methods for most systems containing first-row atoms, while for systems
      containing second-row atoms, ccCA is an improvement over Gn model chemistries.

PMID- 16999520
TI  - Ground and electronically excited states of methyl hydroperoxide: comparison with
      hydrogen peroxide.
AB  - Equilibrium geometries of the ground states of hydrogen peroxide (H(2)O(2)) and
      methyl hydroperoxide (CH(3)OOH) have been obtained using quadratic configuration
      interaction methods with correlation-consistent basis sets. These results are
      compared with experiments and prior calculations. The dipole moments of the
      ground states of these two molecules have been calculated. The results illustrate
      the sensitivity of this quantity to molecular geometry. Several excited states of
      H(2)O(2) and CH(3)OOH were calculated using the equation-of-motion coupled
      cluster singles-and-doubles method. Aside from vertical excitation energies,
      excited state energies along the O-O, O-H, and C-O dissociation pathways were
      calculated. The results are expected to be of assistance in resolving
      discrepancies in the experimental interpretation of the UV absorption spectrum
      and photodissociation of CH(3)OOH.

PMID- 16999521
TI  - Quantum Monte Carlo calculations of the dissociation energy of the water dimer.
AB  - We report diffusion quantum Monte Carlo (DMC) calculations of the equilibrium
      dissociation energy D(e) of the water dimer. The dissociation energy measured
      experimentally, D(0), can be estimated from D(e) by adding a correction for
      vibrational effects. Using the measured dissociation energy and the modern value
      of the vibrational energy Mas et al., [J. Chem. Phys. 113, 6687 (2000)] leads to
      D(e)=5.00+/-0.7 kcal mol(-1), although the result Curtiss et al., [J. Chem. Phys.
      71, 2703 (1979)] D(e)=5.44+/-0.7 kcal mol(-1), which uses an earlier estimate of
      the vibrational energy, has been widely quoted. High-level coupled cluster
      calculations Klopper et al., [Phys. Chem. Chem. Phys. 2, 2227 (2000)] have
      yielded D(e)=5.02+/-0.05 kcal mol(-1). In an attempt to shed new light on this
      old problem, we have performed all-electron DMC calculations on the water monomer
      and dimer using Slater-Jastrow wave functions with both Hartree-Fock
      approximation (HF) and B3LYP density functional theory single-particle orbitals.
      We obtain equilibrium dissociation energies for the dimer of 5.02+/-0.18 kcal
      mol(-1) (HF orbitals) and 5.21+/-0.18 kcal mol(-1) (B3LYP orbitals), in good
      agreement with the coupled cluster results.

PMID- 16999522
TI  - Ab initio calculations on SCl2 and low-lying cationic states of SCl2+: Franck
      Condon simulation of the UV photoelectron spectrum of SCl2.
AB  - Geometry optimization calculations were carried out on the (approximate)X (1)A(1)
      state of SCl(2) and the (approximate)X(2)B(1), (approximate)A(2)B(2),
      (approximate)B(2)A(1), (approximate)C(2)A(1), (approximate)D(2)A(2), and
      (approximate)E (2)B(2) states of SCl(2) (+) at the restricted-spin coupled
      cluster single-double plus perturbative triple excitation [RCCSD(T)] level with
      basis sets of up to the augmented correlation-consistent polarized quintuple-zeta
      [aug-cc-pV(5+d)Z] quality. Effects of core electron correlation, basis set
      extension to the complete basis set limit, and relativistic contributions on
      computed minimum-energy geometrical parameters and/or relative electronic
      energies were also investigated. RCCSD(T) potential energy functions (PEFs) were
      calculated for the (approximate)X (1)A(1) state of SCl(2) and the low-lying
      states of SCl(2)(+) listed above employing the aug-cc-pV(5+d)Z basis set.
      Anharmonic vibrational wave functions of these neutral and cationic states of
      SCl(2), and Franck-Condon (FC) factors of the lowest four one-electron allowed
      neutral photoionizations were computed employing the RCCSD(T)aug-cc-pV(5+d)Z
      PEFs. Calculated FC factors with allowance for the Duschinsky rotation and
      anharmonicity were used to simulate the first four photoelectron (PE) bands of
      SCl(2). The agreement between simulated and observed He I PE spectra reported by
      Colton et al. [J. Electron Spectrosc. Relat. Phenom. 3, 345 (1974)] and Solouki
      et al. [Chem. Phys. Lett. 26, 20 (1974)] is excellent. However, our FC spectral
      simulations indicate that the first observed vibrational component in the first
      PE band of SCl(2) is a "hot" band arising from the
      SCl(2)(+)(approximate)X(2)B(1)(0,0,0)<--SCl(2)(approximate)X (1)A(1)(1,0,0)
      ionization. Consequently, the experimental adiabatic ionization energy of SCl(2)
      is revised to 9.55+/-0.01 eV, in excellent agreement with results obtained from
      state-of-the-art ab initio calculations in this work.

PMID- 16999523
TI  - Ab initio calculations on SF2 and its low-lying cationic states: anharmonic
      Franck-Condon simulation of the UV photoelectron spectrum of SF2.
AB  - Geometry optimization calculations were carried out on the (approximate)X(1)A(1)
      state of SF2 and the (approximate)X(2)B(1), (approximate)A(2)A(1),
      (approximate)B(2)B(2), (approximate)C(2)B(2), (approximate)D(2)A(1), and
      (approximate)E(2)A(2) states of SF2(+) employing the restricted-spin coupled
      cluster single-double plus perturbative triple excitation [RCCSD(T)] method and
      basis sets of up to the augmented correlation-consistent polarized quintuple-zeta
      [aug-cc-pV(5+d)Z] quality. Effects of core electron (S 2s(2)2p(6) and F 1s(2)
      electrons) correlation and basis set extension to the complete basis set limit on
      the computed minimum-energy geometries and relative electronic energies
      (adiabatic and vertical ionization energies) were investigated. RCCSD(T)
      potential energy functions (PEFs) were calculated for the (approximate)X(1)A(1)
      state of SF2 and the low-lying states of SF2(+) listed above employing the aug-cc
      pV(5+d)Z and aug-cc-pV5Z basis sets for S and F, respectively. Anharmonic
      vibrational wave functions of these neutral and cationic states of SF2, and
      Franck-Condon (FC) factors of the lowest four one-electron allowed neutral
      photoionizations were computed employing the RCCSD(T) PEFs. Calculated FC factors
      with allowance for Duschinsky rotation and anharmonicity were used to simulate
      the first four photoelectron bands of SF2. The agreement between the simulated
      and observed first bands in the He I photoelectron spectrum reported by de Leeuw
      et al. [Chem. Phys. 34, 287 (1978)] is excellent. Our calculations largely
      support assignments made by de Leeuw et al. on the higher ionization energy bands
      of SF2.

PMID- 16999524
TI  - Atmospheric reactions Cl+CH3-(CH2)n-OH (n=0-4): a kinetic and theoretical study.
AB  - The reactions of Cl with a series of linear alcohols: methanol (k1), ethanol
      (k2), 1-propanol (k3), 1-butanol (k4), and 1-pentanol (k5) were investigated as a
      function of temperature in the range of 264-382 K by laser photolysis-resonance
      fluorescence. The obtained kinetic data were used to derive the following
      Arrhenius expressions: k1=(3.55+/-0.22)x10(-10) exp[-(559+/-40)T], k2=(5.25+/
      0.52)x10(-11) exp[(190+/-68)T], k3=(2.63+/-0.21)x10(-11) exp[(525+/-51)T],
      k4=(3.12+/-0.31)x10(-11) exp[(548+/-65)T], and k5=(3.97+/-0.48)x10(-11)
      exp[(533+/-77)T] (in units of cm(3) molecule(-1) s(-1)). To our knowledge, these
      are the first absolute kinetic data reported for 1-butanol and 1-pentanol and
      also the first kinetic study as a function of temperature for these two
      compounds. Results, mechanism, and tropospheric implications are discussed and
      compared with the reported reactivity with OH radicals. Moreover, a theoretical
      insight into the mechanisms of these reactions has also been pursued through ab
      initio Moller-Plesset second-order perturbation treatment calculations with 6
      311G** basis sets. Optimized geometries and vibrational frequencies have been
      obtained for transition states and molecular complexes appearing along the
      different reaction pathways. Furthermore, molecular energies have been calculated
      at quadratic configuration interaction with single, double, and triple
      excitations level in order to get an estimation of the activation energies.

PMID- 16999525
TI  - Characterization of singlet ground and low-lying electronic excited states of
      phosphaethyne and isophosphaethyne.
AB  - The singlet ground ((approximate)X(1)Sigma1+) and excited (1Sigma-,1Delta) states
      of HCP and HPC have been systematically investigated using ab initio molecular
      electronic structure theory. For the ground state, geometries of the two linear
      stationary points have been optimized and physical properties have been predicted
      utilizing restricted self-consistent field theory, coupled cluster theory with
      single and double excitations (CCSD), CCSD with perturbative triple corrections
      [CCSD(T)], and CCSD with partial iterative triple excitations (CCSDT-3 and CC3).
      Physical properties computed for the global minimum ((approximate)X(1)Sigma+HCP)
      include harmonic vibrational frequencies with the cc-pV5Z CCSD(T) method of
      omega1=3344 cm(-1), omega2=689 cm(-1), and omega3=1298 cm(-1). Linear HPC, a
      stationary point of Hessian index 2, is predicted to lie 75.2 kcal mol(-1) above
      the global minimum HCP. The dissociation energy D0[HCP((approximate)X(1)Sigma+)-
      >H(2S)+CP(X2Sigma+)] of HCP is predicted to be 119.0 kcal mol(-1), which is very
      close to the experimental lower limit of 119.1 kcal mol(-1). Eight singlet
      excited states were examined and their physical properties were determined
      employing three equation-of-motion coupled cluster methods (EOM-CCSD, EOM-CCSDT
      3, and EOM-CC3). Four stationary points were located on the lowest-lying excited
      state potential energy surface, 1Sigma- -->1A", with excitation energies Te of
      101.4 kcal mol(-1) (1A"HCP), 104.6 kcal mol(-1)(1Sigma-HCP), 122.3 kcal mol(
      1)(1A" HPC), and 171.6 kcal mol(-1)(1Sigma-HPC) at the cc-pVQZ EOM-CCSDT-3 level
      of theory. The physical properties of the 1A" state with a predicted bond angle
      of 129.5 degrees compare well with the experimentally reported first singlet
      state ((approximate)A1A"). The excitation energy predicted for this excitation is
      T0=99.4 kcal mol(-1) (34 800 cm(-1),4.31 eV), in essentially perfect agreement
      with the experimental value of T0=99.3 kcal mol(-1)(34 746 cm(-1),4.308 eV). For
      the second lowest-lying excited singlet surface, 1Delta-->1A', four stationary
      points were found with Te values of 111.2 kcal mol(-1) (2(1)A' HCP), 112.4 kcal
      mol(-1) (1Delta HPC), 125.6 kcal mol(-1)(2(1)A' HCP), and 177.8 kcal mol(
      1)(1Delta HPC). The predicted CP bond length and frequencies of the 2(1)A' state
      with a bond angle of 89.8 degrees (1.707 A, 666 and 979 cm(-1)) compare
      reasonably well with those for the experimentally reported (approximate)C(1)A'
      state (1.69 A, 615 and 969 cm(-1)). However, the excitation energy and bond angle
      do not agree well: theoretical values of 108.7 kcal mol(-1) and 89.8 degrees
      versus experimental values of 115.1 kcal mol(-1) and 113 degrees. of 115.1 kcal
      mol(-1) and 113 degrees.

PMID- 16999527
TI  - Reactions of mixed silver-gold cluster cations AgmAun + (m+n=4,5,6) with CO:
      radiative association kinetics and density functional theory computations.
AB  - Near thermal energy reactive collisions of small mixed metal cluster cations
      Ag(m)Au(n) (+) (m+n=4, 5, and 6) with carbon monoxide have been studied in the
      room temperature Penning trap of a Fourier transform ion-cyclotron-resonance mass
      spectrometer as a function of cluster size and composition. The tetrameric
      species AgAu(3) (+) and Ag(2)Au(2) (+) are found to react dissociatively by way
      of Au or Ag atom loss, respectively, to form the cluster carbonyl AgAu(2)CO(+).
      In contrast, measurements on a selection of pentamers and hexamers show that CO
      is added with absolute rate constants that decrease with increasing silver
      content. Experimentally determined absolute rate constants for CO adsorption were
      analyzed using the radiative association kinetics model to obtain cluster cation
      CO binding energies ranging from 0.77 to 1.09 eV. High-level ab initio density
      functional theory (DFT) computations identifying the lowest-energy cluster
      isomers and the respective CO adsorption energies are in good agreement with the
      experimental findings clearly showing that CO binds in a "head-on" fashion to a
      gold atom in the mixed clusters. DFT exploration of reaction pathways in the case
      of Ag(2)Au(2) (+) suggests that exoergicities are high enough to access the
      minimum energy products for all reactive clusters probed.

PMID- 16999526
TI  - Geometric and electronic properties of endohedral Si @ C74.
AB  - The generalized gradient approximation based on density functional theory is used
      to analyze the geometric and electronic properties of Si @ C(74). It is found
      that among the five possible optimized geometries of Si @ C(74), the most
      favorable endohedral site of Si atom is under the center of a pentagon ring on
      the sigma(h) plane, i.e., Si @ C(74)-5, which is different from the center stable
      site for Si in C(74) calculated by the semiempirical molecular orbital
      calculations and molecular mechanics calculations, and it is also different from
      the stable site, i.e., under a [6, 6] bond along the C(2) axis on the sigma(h)
      plane in C(74) for metal atoms Ba, Ca, and Eu. The deformation charge density on
      the sigma(h) plane reveals that the Si-C bonds in Si @ C(74)-5 have covalent
      character, while the Mulliken charge analysis together with a longer Si-C bond
      length reveals that the Si-C bonds in Si @ C(74)-5 have ionic character.
      Therefore, we infer that Si-C bonds in Si @ C(74)-5 contain both covalent and
      ionic characters.

PMID- 16999528
TI  - Study of the molecular structure, ionization spectrum, and electronic wave
      function of 1,3-butadiene using electron momentum spectroscopy and benchmark
      Dyson orbital theories.
AB  - The scope of the present work is to reconcile electron momentum spectroscopy with
      elementary thermodynamics, and refute conclusions drawn by Saha et al. in J.
      Chem. Phys. 123, 124315 (2005) regarding fingerprints of the gauche
      conformational isomer of 1,3-butadiene in electron momentum distributions that
      were experimentally inferred from gas phase (e,2e) measurements on this compound
      [M. J. Brunger et al., J. Chem. Phys. 108, 1859 (1998)]. Our analysis is based on
      thorough calculations of one-electron and shake-up ionization spectra employing
      one-particle Green's function theory along with the benchmark third-order
      algebraic diagrammatic construction [ADC(3)] scheme. Accurate spherically
      averaged electron momentum distributions are correspondingly computed from the
      related Dyson orbitals. The ionization spectra and Dyson orbital momentum
      distributions that were computed for the trans-conformer of 1,3-butadiene alone
      are amply sufficient to quantitatively unravel the shape of all available
      experimental (e,2e) electron momentum distributions. A comparison of theoretical
      ADC(3) spectra for the s-trans and gauche energy minima with inner- and outer
      valence high-resolution photoelectron measurements employing a synchrotron
      radiation beam [D. M. P. Holland et al., J. Phys. B 29, 3091 (1996)] demonstrates
      that the gauche structure is incompatible with ionization experiments in high
      vacuum conditions and at standard temperatures. On the other hand, outer-valence
      Green's function calculations on the s-trans energy minimum form and approaching
      basis set completeness provide highly quantitative insights, within approximately
      0.2 eV accuracy, into the available experimental one-electron ionization
      energies. At last, analysis of the angular dependence of relative (e,2e)
      ionization intensities nicely confirms the presence of one rather intense pi(-2)
      pi(*+1) satellite at approximately 13.1 eV in the ionization spectrum of the s
      trans conformer.

PMID- 16999529
TI  - Rovibrational photoionization dynamics of methyl and its isotopomers studied by
      high-resolution photoionization and photoelectron spectroscopy.
AB  - High-resolution photoionization and pulsed-field-ionization zero-kinetic-energy
      photoelectron spectra of CH(3), CH(2)D, CHD(2), and CD(3) have been recorded in
      the vicinity of the first adiabatic ionization threshold following single-photon
      excitation from the ground neutral state using a narrow-bandwidth vacuum
      ultraviolet laser. The radicals were produced from the precursor molecules methyl
      bromide, methyl-iodide, dimethyl-thioether, acetone, and nitromethane by 193 nm
      excimer photolysis in a quartz capillary and were subsequently cooled to a
      rotational temperature T(rot) approximately equal to 30 K in a supersonic
      expansion. Nitromethane was identified as a particularly suitable photolytic
      precursor of methyl for studies by photoionization and threshold photoelectron
      spectroscopy. Thanks to the cold rotational temperature reached in the supersonic
      expansion, the rotational structure of the threshold ionization spectra could be
      resolved, and the photoionization dynamics investigated. Rydberg series
      converging on excited rotational levels of CH(3) (+) could be observed in the
      range of principal quantum number n=30-50, and both rotational autoionization and
      predissociation were identified as decay processes in the threshold region. The
      observed photoionization transitions can be understood in the realm of an orbital
      model for direct ionization but the intensity distributions can only be fully
      accounted for if the rotational channel interactions mediated by the quadrupole
      of the cation are considered. Improved values of the adiabatic ionization
      thresholds were derived for all isotopomers [CH(3): 79 356.2(15) cm(-1), CH(2)D:
      79 338.8(15) cm(-1), CHD(2): 79 319.1(15) cm(-1), and CD(3): 79 296.4(15) cm(
      1)].

PMID- 16999530
TI  - Improved results for the excited states of nitric oxide, including the B/C
      avoided crossing.
AB  - The potential energy surfaces of ten electronic states of nitric oxide (NO) have
      been reexamined computationally, with state energies calculated using ab initio
      multireference methods. Our wave function expansions of 10x10(6) configurations
      improve upon the results of de Vivie and Peyerimhoff [J. Chem. Phys. 89, 3028
      (1988)], who obtained excellent results from expansions of 16 000 configurations
      in 1988. We present results for the adiabatic properties r(e), B(e), T(e), and
      omega(e), demonstrating standard errors of 0.012 A, 0.026 cm(-1), 620 cm(-1), and
      41 cm(-1), respectively. Vertical excitation energies and oscillator strengths
      are also presented, as are potential energy surface curves, with special
      attention to the B/C avoided crossing. The technical issue of state-averaging
      effects is also discussed.

PMID- 16999531
TI  - The microwave spectrum of a two-top peptide mimetic: the N-acetyl alanine methyl
      ester molecule.
AB  - The rotational spectrum of N-acetyl alanine methyl ester, a derivative of the
      biomimetic, N-acetyl alanine N'-methyl amide or alanine dipeptide, has been
      measured using a mini Fourier transform spectrometer between 9 and 25 GHz as part
      of a project undertaken to determine the conformational structures of various
      peptide mimetics from the torsion-rotation parameters of low-barrier methyl tops.
      Torsion-rotation splittings from two of the three methyl tops capping the acetyl
      end of the -NH-C(=O)- and the methoxy end of -C(=O)-O- groups account for most of
      the observed lines. In addition to the AA state, two E states have been assigned
      and include an AE state having a torsional barrier of 396.45(7) cm(-1) (methoxy
      rotor) and an EA state having a barrier of 64.96(4) cm(-1) (acetyl rotor). The
      observed torsional barriers and rotational constants of alanine dipeptide and its
      methyl ester are compared with predictions from Moller-Plesset second-order
      perturbation theory (MP2) and density functional theory (DFT) in an effort to
      explore systematic errors at the two levels of theory. After accounting for zero
      point energy differences, the torsional barriers at the MP2/cc-pVTZ level are in
      excellent agreement with experiment for the acetyl and methoxy groups while DFT
      predictions range from 8% to 80% too high or low. DFT is found to consistently
      overestimate the overall molecular size while MP2 methods give structures that
      are undersized. Structural discrepancies of similar magnitude are evident in
      previous DFT results of crystalline peptides.

PMID- 16999532
TI  - Torsion-vibration coupling in methanol: the adiabatic approximation and
      intramolecular vibrational redistribution scaling.
AB  - The four-dimensional model Hamiltonian of Wang and Perry [J. Chem. Phys. 109,
      10795 (1998)] is used to compare the approximate adiabatic separation of the
      torsion and CH stretches in methanol to an exact solution of the same
      Hamiltonian. The adiabatic approximation accounts for the pattern of the energy
      levels in the lowest torsional states, including the inverted tunneling
      splittings, but does not account for the pattern of systematic two- and four-fold
      near degeneracies at high torsional excitation. In the adiabatic basis, the
      nonadiabatic couplings mix the torsional and vibrational degrees of freedom and
      hence are a source for intramolecular vibrational redistribution (IVR). These IVR
      matrix elements are found to decrease by only a factor of 2 or 3 with each higher
      coupling order, in agreement with the results of Pearman and Gruebele [Z. Phys.
      Chem. Munich 214, 1439 (2000)]. This gentle scaling behavior, which contrasts
      with a steeper falloff with coupling order in more rigid molecules, points to a
      more important role for direct high-order couplings in torsional molecules. In
      this model, the scaling behavior derives from a single coupling term that is low
      order in the torsional angular momentum in combination with one-dimensional
      torsional functions that include contributions from many torsional angular
      momenta.

PMID- 16999533
TI  - Temperature and density dependence of the light and heavy water ultraviolet
      absorption edge.
AB  - Characteristics of the ultraviolet absorption band edge of high-pressure light
      and heavy water are reported over the temperature range of 25-400 degrees C,
      extending into the supercritical regime. A gradual redshift in the absorption
      band edge of approximately 0.6 eV is observed with increasing temperature. This
      shift cannot be explained by vibrational hot band growth or changes in the degree
      of Rayleigh scattering with increasing temperature, and is ascribed to a shift of
      the electronic transition energy. The density dependence for the absorption edge
      in 400 degrees C supercritical water was also examined, and showed a surprising
      approximately 0.1 eV blueshift over a factor of 3.5 decrease in density. This
      shift may be due to a narrowing of the absorption spectrum with decreasing
      density. It is proposed that the previously reported "red tail" of the water
      absorption extending into the near ultraviolet and visible could be attributed to
      preresonant Rayleigh scattering, and that the true onset of liquid water
      absorption is approximately 5.8 eV at 25 degrees C.

PMID- 16999534
TI  - Theoretical modeling of postionization fragmentation of rare-gas trimer cations.
AB  - The dynamics of ionic rare-gas trimers (Ar(3) (+), Kr(3) (+), and Xe(3) (+))
      produced by a sudden ionization of neutral precursors is investigated
      theoretically with a hybrid classical-quantum method for solving the equations of
      motion governed by a Hamiltonian obtained from a previously tested diatomics-in
      molecules model. Initial conditions are selected with Monte Carlo sampling. Two
      possibilities for generating the initial electronic state are considered:
      diabatic (local) and adiabatic (delocalized). The dynamics generally leads to
      fragmentation, producing either monomer ions or dimer ions in a relatively short
      time; however, a large number of long-lived metastable trimer ions are also seen
      in some cases. We have analyzed the dynamics with respect to the fraction of
      monomer ions produced, the distribution of the kinetic energy of the products,
      and the distribution of fragmentation times of the trimers. Initial diabatic
      ionization is associated with much faster fragmentation than adiabatic
      ionization. Spin-orbit coupling plays an important role in the fragmentation
      dynamics.

PMID- 16999535
TI  - Stability of rare gas structure H clathrate hydrates.
AB  - Molecular dynamics simulations are used to study the stability of structure H
      (sH) clathrate hydrates with the rare gases Ne, Ar, Kr, and Xe. Simulations on a
      3 x 3 x 3 sH unit cell replica are performed at ambient pressure at 40 and 100 K
      temperatures. The small and medium (s+m) cages of the sH unit cell are assigned
      rare gas guest occupancies of 1 and for large (l) cages guest occupancies of 1-6
      are considered. Radial distribution functions for guest pairs with occupancies in
      the l-l, l-(s+m), and (s+m)-(s+m) cages are presented. The unit cell volumes and
      configurational energies are studied as a function of large cage occupancy for
      the rare gases. Free energy calculations are carried out to determine the
      stability of clathrates for large cage occupancies at 100 K and 1 bar and 20 kbar
      pressures. These studies show that the most stable argon clathrate has five
      guests in the large cages. For krypton and xenon the most stable configurations
      have three and two guests in the large cages, respectively.

PMID- 16999536
TI  - On the mutual diffusion properties of ethanol-water mixtures.
AB  - The structural organization, the number of hydrogen bonds (H bond), and the self-
      and mutual diffusion coefficients of ethanol-water mixtures were studied by
      molecular dynamics simulation. It was found that both the numbers of H bonds per
      water and per ethanol decrease as the mole fraction of ethanol increases. The
      composition dependences and the relationships between the self- and the mutual
      diffusion coefficients were further discussed. The self-diffusion coefficient of
      water has a large drop as the concentration of ethanol increases from 0 to 0.3
      and then it nearly keeps constant, while that of ethanol has a minimum around
      ethanol mole fraction of 0.5. The mutual diffusion coefficient could be divided
      into two parts, the kinematic factor and the thermodynamic factor. Both the
      kinematic and thermodynamic factors for ethanol-water mixtures were calculated.
      It was found that the change trend of mutual diffusion coefficients with the
      composition is mainly dependent on the thermodynamic factors.

PMID- 16999537
TI  - Self-consistent Ornstein-Zernike approximation for molecules with soft cores.
AB  - The self-consistent Ornstein-Zernike approximation (SCOZA) is an accurate liquid
      state theory. So far it has been tied to interactions composed of hard core
      repulsion and long-range attraction, whereas real molecules have soft core
      repulsion at short distances. In the present work, this is taken into account
      through the introduction of an effective hard core with a diameter that depends
      upon temperature only. It is found that the contribution to the configurational
      internal energy due to the repulsive reference fluid is of prime importance and
      must be included in the thermodynamic self-consistency requirement on which SCOZA
      is based. An approximate but accurate evaluation of this contribution relies on
      the virial theorem to gauge the amplitude of the pair distribution function close
      to the molecular surface. Finally, the SCOZA equation is transformed by which the
      problem is reformulated in terms of the usual SCOZA with fixed hard core
      reference system and temperature-dependent interaction.

PMID- 16999538
TI  - Phase behavior of dipolar fluids from a modified statistical associating fluid
      theory for potentials of variable range.
AB  - A statistical associating fluid theory for potentials of variable range to model
      dipolar fluids is presented. The new theory, termed the SAFT-VR+D equation (the
      statistical associating fluid theory for potentials of variable range plus
      dipole), explicitly accounts for dipolar interactions and their effect on the
      structure of the fluid. This is achieved through the use of the generalized mean
      spherical approximation (GMSA) to describe a reference fluid of dipolar square
      well segments. Isothermal-isobaric and Gibbs ensemble Monte Carlo simulations
      have been performed in order to test the new theoretical approach. Predictions
      for the thermodynamic properties and phase behavior of dipolar square-well
      monomer and chain fluids, in which one or more segments are dipolar, are
      considered and compared with new computer simulation data. The results show that
      the equation of state in general provides a good description of the phase
      behavior of dipolar monomer and chain fluids. Some deviations are seen between
      the simulation data and theoretical predictions for monomer fluids with large
      dipole moments and for molecules composed of segments with dipoles in different
      orientations. This is addressed through the replacement of the GMSA by the
      linearized exponential approximation.

PMID- 16999539
TI  - Vapor-liquid equilibrium of hexadecapolar fluids from a perturbation-based
      equation of state.
AB  - In this work a numerically tractable expression for the interaction potential
      between two point hexadecapoles with octahedral symmetry and a molecular-based
      equation of state derived by perturbation theory for hexadecapolar fluids are
      presented. The polar system is modeled by square-well particles with a point
      hexadecapole with octahedral symmetry at their centers. This equation of state is
      analytical in the state variables and in the potential parameters and allows us
      to study the effects of the hexadecapolar moment strength on the thermodynamic
      properties and liquid-vapor phase diagram. The equation presented here is applied
      to the thermodynamics of sulfur hexafluoride and gives very good predictions for
      the saturation pressures and the vapor-liquid phase diagram.

PMID- 16999540
TI  - Binary to unary transition problem in nucleation theory.
AB  - The limiting behavior in binary nucleation theory when one component vanishes is
      examined. Failure of the traditional continuum theory to predict the transition
      from binary to unary nucleation is due to breakdown of the continuum
      approximation. A semidiscrete model is constructed for the transition regime. For
      binary systems of arbitrary composition, a general formula that combines the semi
      discrete and continuum nucleation rates is proposed. Comparison with the exact
      solution calculated using a fully discrete matrix method shows good agreement.

PMID- 16999541
TI  - Multiexponential decay autocorrelation function in dynamic light scattering in
      near-critical ternary liquid mixture.
AB  - The dynamic structure factor of a ternary liquid mixture is calculated from the
      theory of thermodynamic fluctuations with the help of linearized hydrodynamic
      equations. The theoretical model allows evaluating and classifying the transport
      properties near a critical solution point of a ternary mixture. In the vicinity
      of the critical solution point, experimental dynamic light scattering
      measurements reveal two hydrodynamic relaxation modes with well-separated
      characteristic relaxation times. From the autocorrelation functions, we can
      determine two effective diffusivities D(1) and D(2). As theoretically predicted
      by a model developed in this work, one of these two modes can be associated with
      thermal diffusion and the other with mass diffusion. In the special case of an
      incompressible liquid mixture limit, D(1) and D(2) are decoupled, becoming
      thermodiffusion coefficient D(T) and mutual mass diffusion coefficient D(ij). A
      possible physical meaning of D(1) and D(2) for a ternary mixture is discussed.

PMID- 16999542
TI  - Shear dynamics of hydration layers.
AB  - Molecular dynamics (MD) simulations have been performed to investigate the shear
      dynamics of hydration layers of the thickness of D=0.61-2.44 nm confined between
      two mica surfaces. Emphases are placed on the external shear response and
      internal relaxation properties of aqueous films. For D=0.92-2.44 nm liquid phase,
      the shear responses are fluidic and similar to those observed in surface force
      balance experiments [U. Raviv and J. Klein, Science 297, 1540 (2002)]. However,
      for the bilayer ice (D=0.61 nm) [Y. S. Leng and P. T. Cummings, J. Chem. Phys.
      124, 74711 (2006)] significant shear enhancement and shear thinning over a wide
      range of shear rates in MD regime are observed. The rotational relaxation time of
      water molecules in this bilayer ice is found to be as high as 0.017 ms (10(-5)
      s). Extrapolating the shear rate to the inverse of this longest relaxation time,
      we obtain a very high shear viscosity for the bilayer ice, which is also observed
      quite recently for D< or =0.6+/-0.3 nm hydration layers [H. Sakuma et al., Phys.
      Rev. Lett. 96, 46104 (2006)]. We further investigate the boundary slip of water
      molecules and hydrated K(+) ions and concluded that no-slip boundary condition
      should hold for aqueous salt solution under extreme confinement between
      hydrophilic mica surfaces, provided that the confined film is of Newtonian fluid.

PMID- 16999543
TI  - First-principles theoretical analysis of silyl radical diffusion on silicon
      surfaces.
AB  - We report results from a detailed analysis of the fundamental radical precursor
      diffusion processes on silicon surfaces and discuss their implications for the
      surface smoothness of hydrogenated amorphous silicon (a-Si:H) thin films. The
      analysis is based on a synergistic combination of first-principles density
      functional theory (DFT) calculations of SiH(3) radical migration on the hydrogen
      terminated Si(001)-(2 x 1) surface with molecular-dynamics (MD) simulations of
      SiH(3) radical precursor migration on surfaces of a-Si:H films. Our DFT
      calculations yield activation energies for SiH(3) migration that range from 0.18
      to 0.89 eV depending on the local electronic environment on the Si(001)-(2 x 1):H
      surface. In particular, when no substantial surface relaxation (Si-Si bond
      breaking or formation) accompanies the hopping of the SiH(3) radical the
      activation barriers are highest, whereas hopping between nearest-neighbor
      overcoordinated surface Si atoms results in the lowest radical diffusion barrier
      of 0.18 eV; this low barrier is consistent with the activation barrier for SiH(3)
      migration through overcoordinated sites on the a-Si:H surface. Specifically, the
      analysis of the MD simulations of SiH(3) radical migration on a-Si:H surfaces
      yields an effective diffusion barrier of 0.16 eV, allowing for the rapid
      migration of the SiH(3) radical prior to its incorporation in surface valleys;
      rapid migration and subsequent incorporation constitute the two-step mechanism
      responsible for the smoothness of plasma deposited a-Si:H thin films.

PMID- 16999544
TI  - Motion of a branched polymer chain in confinement: a Monte Carlo study.
AB  - The aim of the study was a theoretical investigation of the polymer molecules
      located between two parallel and impenetrable surfaces which were also attractive
      for polymer segments. The chains were constructed of identical segments and were
      restricted to knots of a simple cubic lattice. Since the chains were at good
      solvent conditions the only interactions between the segments of the chain were
      the excluded volume. The properties of the model chains were determined by means
      of Monte Carlo simulations with a sampling algorithm based on the chain's local
      changes of conformation. The differences and similarities in the structure for
      different adsorption regimes and the size of the slit were shown and discussed.
      It was observed that at certain conditions the polymer chain was adsorbed at one
      of the confining surfaces, and then after a certain period of time it detached
      from this surface and approached the opposite wall; this switch was repeated many
      times. The influence of the strength of the adsorption, the size of the slit, and
      the chain's length on the frequency of these jumps were determined. The mechanism
      of the chain's motion during the switch was also shown.

PMID- 16999545
TI  - Perturbation theory of Phi-value analysis of two-state protein folding: relation
      between p fold and Phi values.
AB  - In protein folding, the transition state ensemble is defined as the set of
      conformations with p(fold)=12, where the p(fold) of a conformation is the
      probability that starting from this conformation the protein folds before it
      unfolds. Experimentally, this ensemble is probed by the Phi-value analysis, where
      Phi is the ratio of the changes in the logarithms of the folding rate and the
      equilibrium constant when the system is perturbed by a mutation. We show that for
      a two-state protein the Phi value can be expressed in terms of the perturbation
      and only the first two eigenfunctions of the evolution operator (e.g., a rate
      matrix) of the wild-type protein. The first eigenfunction is the equilibrium
      probability distribution while the second is proportional to p(fold), thus
      establishing a formal relation between p(fold) and Phi values. In addition to
      providing insight into the theoretical foundation of the Phi-value analysis, our
      results may prove practically useful in performing such analyses within the
      framework of models containing a large number of states.

PMID- 16999546
TI  - Molecular diffusion in liquid crystals and chiral discrimination. II. Model
      calculations.
AB  - We perform model calculations of the macroscopic diffusion coefficient for a
      solute moving in a chiral nematic (cholesteric) liquid crystal (LC) phase
      applying the methodology developed by Frezzato et al. [J. Chem. Phys. 122, 164904
      (2005)]. Three types of solutes with different features are studied: ellipsoid
      [roto-translational coupling (RTC) absent], bent rod (RTC present), and two-blade
      propeller (with RTC and chiral shape). For each prototype molecule we estimate
      the effect of cholesteric helix pitch and local order on the diffusion along the
      helix axis. For the ellipsoidal particle we find that translational diffusion is
      slowed down by rotation around the short axis. For the chiral solute we show that
      the enantiomer with shape chirality opposite to that of the LC phase is slowed
      down more than the other. This provides a proof of principle of the possibility
      of separating the two enantiomers via transport in a suitable chiral medium.

PMID- 16999547
TI  - Organic-inorganic telechelic molecules: solution properties from simulations.
AB  - We report molecular dynamics simulations for telechelic molecules composed of two
      polyhedral oligomeric silsesquioxane (POSS) cages connected by one hydrocarbon
      backbone dissolved in liquid normal hexane. Silsesquioxanes are novel hybrid
      organic-inorganic molecules that are useful as building blocks for the synthesis
      of nanostructured materials. By including POSS molecules within a polymeric
      material it is possible to modify mechanical properties such as resistance to
      heat and glass transition temperatures. Unfortunately, the molecular mechanisms
      responsible for these enhancements are at present not completely understood. In
      an effort to elucidate the molecular phenomena responsible for these effects, we
      have studied the conformation of telechelic POSS molecules in solution, as well
      as their self-diffusion coefficients, as a function of the length of the
      hydrocarbon backbone. We focus on molecules in which the radius of gyration of
      the alkane backbone is comparable to the size of the silsesquioxane cages. Our
      results indicate that the backbone has a significant influence on both the
      equilibrium and the transport properties of dissolved telechelic hybrid
      molecules. These observations are useful for developing strategies to direct the
      self-assembly of nanostructured materials.

PMID- 16999548
TI  - Unbinding of the streptavidin-biotin complex by atomic force microscopy: a hybrid
      simulation study.
AB  - A hybrid molecular simulation technique, which combines molecular dynamics and
      continuum mechanics, was used to study the single-molecule unbinding force of a
      streptavidin-biotin complex. The hybrid method enables atomistic simulations of
      unbinding events at the millisecond time scale of atomic force microscopy (AFM)
      experiments. The logarithmic relationship between the unbinding force of the
      streptavidin-biotin complex and the loading rate (the product of cantilever
      spring constant and pulling velocity) in AFM experiments was confirmed by hybrid
      simulations. The unbinding forces, cantilever and tip positions, locations of
      energy barriers, and unbinding pathway were analyzed. Hybrid simulation results
      from this work not only interpret unbinding AFM experiments but also provide
      detailed molecular information not available in AFM experiments.

PMID- 16999549
TI  - Time-convolutionless master equation for mesoscopic electron-phonon systems.
AB  - The time-convolutionless master equation for the electronic populations is
      derived for a generic electron-phonon Hamiltonian. The equation can be used in
      the regimes where the golden rule approach is not applicable. The equation is
      applied to study the electronic relaxation in several models with the finite
      number of normal modes. For such mesoscopic systems the relaxation behavior
      differs substantially from the simple exponential relaxation. In particular, the
      equation shows the appearance of the recurrence phenomena on a time scale
      determined by the slowest mode of the system. The formal results are quite
      general and can be used for a wide range of physical systems. Numerical results
      are presented for a two level system coupled to Ohmic and super-Ohmic baths, as
      well as for a model of charge-transfer dynamics between semiconducting organic
      polymers.

PMID- 16999550
TI  - Simulation of the gyroid phase in off-lattice models of pure diblock copolymer
      melts.
AB  - Particle-based molecular simulations of pure diblock copolymer (DBC) systems were
      performed in continuum space via dissipative particle dynamics and Monte Carlo
      methods for a bead-spring chain model. This model consisted of chains of soft
      repulsive particles often used with dissipative particle dynamics. The gyroid
      phase was successfully simulated in DBC melts at selected conditions provided
      that the simulation box size was commensurate with the gyroid lattice spacing.
      Simulations were concentrated at conditions where the gyroid phase is expected to
      be stable which allowed us to outline approximate phase boundaries. When more
      than one phase was observed by varying simulation box size, thermodynamic
      stability was discerned by comparing the Helmholtz free energy of the competing
      phases. For this purpose, chemical potentials were efficiently simulated via an
      expanded ensemble that gradually inserts/deletes a target chain to/from the
      system. These simulations employed a novel combination of Bennett's [J. Comput.
      Phys. 22, 245 (1976)] acceptance-ratio method to estimate free-energy differences
      and a recently proposed method to get biasing weights that maximize the number of
      times that the target chain is regrown. The analysis of the gyroid nodes revealed
      clear evidence of packing frustration in the form of an (entropically)
      unfavorably overstretching of chains, a phenomenon that has been suggested to
      provide the structural basis for the limited region of stability of the gyroid
      phase in the DBC phase diagram. Finally, the G phase and nodal chain stretching
      were also found in simulations with a completely different DBC particle-based
      model.

PMID- 16999551
TI  - Two-dimensional chiral model for liquid crystals, bent hard needles: a Monte
      Carlo simulation.
AB  - The liquid crystalline behavior of a two dimensional (2D) model of hard needles
      bent into a "zigzag shape" is studied. This model, originally designed to study
      two dimensional chiral segregation, also shows liquid crystalline behavior and
      has some anomalous features which are contrasted in relation to the following:
      (i) Most of the microscopical models used to study liquid crystals have a
      symmetry axis that coincides with a molecular axis; (ii) in three-dimensions,
      chiral molecules can form cholesteric instead of nematic phases; (iii) the
      smectic phase is usually found when attractions are present or at least when the
      molecules have finite volume. Despite the fact that the present 2D model does not
      have any of these characteristics, numerical evidence is found for the occurrence
      of nematic and smectic phases. Since these molecules are athermal, infinitely
      repulsive, and infinitesimally thin, the liquid crystalline characteristics are
      attributed to excluded volume effects. To determine the mesophases of the model,
      both nematic and smectic order parameters as well as distribution functions are
      computed.

PMID- 16999552
TI  - Universal scaling features of spectroscopic constants for diatomic systems.
AB  - Based on a new criterion that was proposed to search for the universality of
      spectroscopic constants for bound ground-state diatomics [R. H. Xie and P. S.
      Hsu, Phys. Rev. Lett. 96, 243201 (2006)], we have found universal scaling
      relations between spectroscopic constants of diatomic systems with s-, p-, and d
      type valence-shell constituents. Our study suggests a useful empirical approach
      for the prediction of molecular spectroscopic constants.

PMID- 16999553
TI  - Comment on "Quasirelativistic theory equivalent to fully relativistic theory" [J.
      Chem. Phys. 123, 241102 (2005)].
AB  - The connection between the exact quasirelativistic approach developed in the
      title reference [W. Kutzelnigg and W. Liu, J. Chem. Phys. 123, 241102 (2005)] and
      the method of elimination of the small component in matrix form developed
      previously by Dyall is explicitly worked out. An equation that links Hermitian
      and non-Hermitian formulations of the exact quasirelativistic theory is derived.
      Besides establishing a kinship between the existing formulations, the proposed
      equation can be employed for the derivation of new formulations of the exact
      quasirelativistic theory.

PMID- 16999555
TI  - Comment on "MMM1D: A method for calculating electrostatic interactions in one
      dimensional periodic geometries" [J. Chem. Phys. 123, 144103 (2005)].
AB  - This comment gives an alternative derivation of the MMM1D method reported by
      Arnold and Holm [J. Chem. Phys.123, 144103 (2005)]. Moreover, several errors in
      expressions presented in the cited paper are identified.

PMID- 16999558
TI  - [Spanish code of good practice for medicinal drug promotion: a deontological
      supervision unit].

PMID- 16999559
TI  - [Hospital pharmacy in Argentina].

PMID- 16999560
TI  - [Comparison of high-resolution liquid chromatography versus microparticle enzyme
      immunoassay for the measurement of sirolimus levels in renal transplantation].
AB  - OBJECTIVE: To compare sirolimus levels measured in whole blood using two
      analytical techniques: high-resolution liquid chromatography and microparticle
      enzyme immunoassay, and to evaluate whether hemoglobin, hematocrit, and time from
      kidney transplantation influence results obtained using the immune-enzymatic
      technique. METHOD: A retrospective, observational study in which all transplanted
      patients with at least one measurement of sirolimus levels using high-resolution
      liquid chromatography or microparticle enzyme immunoassay from October 2004 to
      May 2005 were consecutively included. For statistical comparisons simple linear
      regression, ANCOVA, intra-class correlation coefficient, and the method of
      agreement limits were all used. RESULTS: Ninety-one patients were assessed for a
      total of 307 measurements (median: 2, inter-quartile range: 1-4, range: 1-15) of
      sirolimus levels. The straight-line equation using the linear regression analysis
      was as follows: MEIA = 0.70 (95% CI: 0.39-1.01) + 1.14 (95% CI: 1.10-1.17) x
      HPLC/UV. The intra-class correlation coefficient between both measurements was
      0.955 (95% CI 0.944-0.964). Mean overestimation using enzyme immunoassay was
      24.8% +/- 19.4%. Difference in means between both measurements was 1.9 +/- 1.3
      ng/mL. Agreement limits were established between -0.8 ng/mL (95% CI: -1.05; 
      0.55) and +4.6 ng/mL (95% CI: 4.35; 4.85). Factors such as post-transplant time,
      hemoglobin, and hematocrit did not influence overestimates obtained using enzyme
      immunoassays. These results were not influenced by non-independence in
      measurements. CONCLUSIONS: Despite enzyme immunoassay overestimates in
      establishing sirolimus levels in whole blood, its correlation with chromatography
      is acceptable. Added to its benefits versus chromatographic techniques, this
      renders enzyme immunoassay a good alternative for the measurement of sirolimus
      levels in whole blood.

PMID- 16999561
TI  - [Effect of the concomitant administration of indomethacin or ibuprofen on
      amikacin pharmacokinetics in premature newborns].
AB  - OBJECTIVE: To evaluate whether the concomitant administration of ibuprofen or
      indomethacin plus amikacin may alter the latter drug s pharmacokinetic
      parameters, and hence amikacin plasma levels. METHOD: Retrospective cohort study
      performed by reviewing the medical records of premature children with persistent
      ductus arteriosus receiving amikacin and ibuprofen, or amikacin and indomethacin.
      They were divided up into three groups: group 1: treatment with amikacin went
      before indomethacin or ibuprofen; group 2: simultaneously treated with amikacin
      and indomethacin; group 3: simultaneously treated with amikacin and ibuprofen.
      Pharmacokinetic parameters, distribution volume, and amikacin clearance were
      measured using the PKS program (a non-linear regression method). Half life was
      determined from previous parameters. RESULTS: Twenty-eight patients were
      included. No statistically significant differences were found among
      pharmacokinetic parameters corresponding to each study group. CONCLUSIONS:
      Further studies are needed with a greater number of patients and currently
      recommended doses to assess the influence of indomethacin and ibuprofen in the
      pharmacokinetics of amikacin in premature children with persistent ductus
      arteriosus.

PMID- 16999562
TI  - [Identifying improvement opportunities in the management of hepatitis C].
AB  - OBJECTIVE: Hepatitis C represents a public health concern with more than 170
      million carriers. The goal of this study was to identify improvement
      opportunities in the management of hepatitis C, and the pharmaceutical actions
      performed for the prevention and solution of medication-related problems in
      patients seen at the Pharmaceutical Care Outpatient Unit. METHOD: A longitudinal
      study (January to October 2005) with patients monoinfected by hepatitis C virus
      receiving ribavirin and peginterferon alfa (2a or 2b). Data collection took place
      during the interview at the time of antiviral dispensation. Adverse reactions
      were classified according to CTCEA v3.0 criteria. Iaser methodology was used to
      identify patients with improvement opportunities regarding treatment. RESULTS: In
      all 109 patients and 201 improvement opportunities were identified.
      Pharmacotherapeutic morbidity was identified from adverse events (blood toxicity,
      pseudoflu syndrome, etc.) in 425 occasions; 388 pharmaceutical actions were
      performed, 41.23% to prevent adverse effects and 39.95% to provide patients or
      carers with information. CONCLUSIONS: In all, 99.01% of patients had safety
      problems. Pharmacotherapeutic morbidity from adverse effects was less common than
      reported in clinical trials of these drugs. Most pharmaceutical actions were
      preventive in nature. Iaser methodology allows to identify patients with
      improvement opportunities regarding hepatitis C treatment and the prevention of
      pharmacotherapeutic morbidity.

PMID- 16999563
TI  - [Prevalence and factors associated with preventable adverse drug events leading
      to hospital admission].
AB  - OBJECTIVE: To determine the prevalence of adverse drug events (ADEs) leading to
      hospital admission, and to assess those that were potentially preventable,
      identifying the drug classes involved, types of medication errors and the factors
      associated with the preventable ADEs. METHOD: An observational study, over a six
      month period on ADEs that lead or contributed to hospital admissions, carried out
      in 6 medical units of a university hospital. RESULTS: A total of 259 ADEs were
      detected of which 159 (61.4%) were assessed to be potentially preventable. The
      overall prevalence of admissions directly due to ADEs was of 6.7% (177) and to
      preventable ADEs of 4.7% (125). In addition, 82 ADEs that contributed to hospital
      admission were detected. Risk factors for preventable ADEs were patient age of 65
      74 (OR = 1.40) or = 75 years (OR = 2.70), self-medication (OR = 15.55),
      prescription in primary care (OR = 2,88) and the use of narrow therapeutic index
      drugs (OR = 2.40). The drug classes most frequently involved in preventable ADEs
      were NSAID and aspirin (32.5%), diuretics (15.3%), antihypertensives (9.1%) and
      digoxin (7.7%). Inadequate therapy monitoring (20.7%), prescription of an
      inappropriate drug (15.7%) or of an excessive dosage (12.0%), lack of preventive
      treatment (15.7%), non-adherence (10.6%) and inappropriate self-medication
      (10.1%) were the most commonly identified types of error. CONCLUSIONS: A high
      proportion (4.7%) of hospital admissions are caused by potentially preventable
      ADEs. Results obtained justified the need to adopt measures directed at improving
      surveillance and prescription quality, and educating patients in safe drug use,
      focusing especially on older patients and narrow therapeutic index drugs.

PMID- 16999564
TI  - [Simplified scale for medication adherence related problems in anti-retroviral
      therapy].
AB  - OBJECTIVE: The purpose is to describe an own-developed scale for medication
      adherence evaluation of HIV patients under antiretroviral therapy, and to compare
      it with other previously described methods. METHODS: The six-item scale was
      compared with a pharmacy record about the delivery of medication. Accordance
      between scale and a four-item Morisky-type scale (measure 1) and a percentage of
      doses taken as prescribed during the past two weeks (measure 2) was computed.
      RESULTS: The own-scale showed 93% sensitivity, 70% specificity, a likelihood
      ratio of 3.08 and good agreement compared with the pharmacy record (k = 0.62, p <
      0.001). Agreement between the scale and measure 1 and measure 2 was very weak (k
      = 0.12, p = 0.446 and k = 0.10, p = 0.273 respectively). 39.7% of patients was
      considered as adherent according with the own-scale and was observed correlation
      between adherence and clinical outcomes. CONCLUSION: The scale appears to be a
      valid instrument to check and detect adherence related problems compared with the
      pharmacy medication record. Easiness to use make feasible to consider as an
      adequate tool to detect non-adherent patients or patients with adherence related
      problems into the daily clinical practice.

PMID- 16999565
TI  - [Latex allergy].
AB  - OBJECTIVE: To review the etiology, diagnosis, prevention and treatment of latex
      allergy in the hospital setting, and to establish a list of potentially hazardous
      drugs. METHOD: A literature search was performed. A guide about latex-containing
      drugs (any component) was developed by contacting manufacturers. RESULTS: The
      most relevant factor for latex sensitization is exposure extent. Regarding
      diagnosis the medical history and skin testing are crucial; regarding secondary
      prevention, identifying the various at-risk groups. Immunotherapy is currently
      considered a valid option for the management of this condition. CONCLUSIONS: The
      development of a guide listing latex-containing drugs is essential for the
      primary prevention of allergic reactions to this substance in hospital.

PMID- 16999566
TI  - [Drug-related problems in the emergency department observation area of a third
      level hospital].
AB  - OBJECTIVE: The therapeutic armamentarium of developed countries has experienced a
      great advance; however, increased drug therapy not only provides benefits, as the
      inappropriate use of drugs results in relevant consequences for patients. METHOD:
      A 3-month, descriptive, cross-sectional, randomized study in 125 patients seen at
      the emergency department observation area of a third-level hospital to identify
      drug-related problems (DRPs). A hospital adaptation of Dader s method was used.
      RESULTS: A mean of 0.94 DRPs per patient was obtained. Major DRPs (mDRPs)
      represented 50% of all DRPs; 69.50% of DRPs were avoidable; 44% were moderate,
      38% mild, and 18% serious; 54.4% of patients were admitted to hospital, which
      originated in a mDRP in 25% of cases--this represents 50% of all patients with a
      mDRP. CONCLUSIONS: A significant portion of patients admitted to the observation
      area present there as a result of a DRP.

PMID- 16999567
TI  - [Readministration of drotrecogin alpha in a patient with Crohn's disease].

PMID- 16999568
TI  - [Inappropriate commercial presentation of selected drugs and associated
      overcost].

PMID- 16999569
TI  - [Drug-related problems in a patient with Cushing's disease].

PMID- 16999570
TI  - [Zoledronate-related maxillary osteonecrosis].

PMID- 16999571
TI  - Spike count correlation increases with length of time interval in the presence of
      trial-to-trial variation.
AB  - It has been observed that spike count correlation between two simultaneously
      recorded neurons often increases with the length of time interval examined. Under
      simple assumptions that are roughly consistent with much experimental data, we
      show that this phenomenon may be explained as being due to excess trial-to-trial
      variation. The resulting formula for the correlation is able to predict the
      observed correlation of two neurons recorded from primary visual cortex as a
      function of interval length.

PMID- 16999572
TI  - The spike-triggered average of the integrate-and-fire cell driven by gaussian
      white noise.
AB  - We compute the exact spike-triggered average (STA) of the voltage for the
      nonleaky integrate-and-fire (IF) cell in continuous time, driven by gaussian
      white noise. The computation is based on techniques from the theory of renewal
      processes and continuous-time hidden Markov processes (e.g., the backward and
      forward Fokker-Planck partial differential equations associated with first
      passage time densities). From the STA voltage, it is straightforward to derive
      the STA input current. The theory also gives an explicit asymptotic approximation
      for the STA of the leaky IF cell, valid in the low-noise regime sigma --> 0. We
      consider both the STA and the conditional average voltage given an observed spike
      "doublet" event, that is, two spikes separated by some fixed period of silence.
      In each case, we find that the STA as a function of time-preceding-spike, tau,
      has a square root singularity as tau approaches zero from below and scales
      linearly with the scale of injected noise current. We close by briefly examining
      the discrete-time case, where similar phenomena are observed.

PMID- 16999573
TI  - Low-dimensional maps encoding dynamics in entorhinal cortex and hippocampus.
AB  - Cells that produce intrinsic theta oscillations often contain the
      hyperpolarization-activated current I(h). In this article, we use models and
      dynamic clamp experiments to investigate the synchronization properties of two
      such cells (stellate cells of the entorhinal cortex and O-LM cells of the
      hippocampus) in networks with fast-spiking (FS) interneurons. The model we use
      for stellate cells and O-LM cells is the same, but the stellate cells are
      excitatory and the O-LM cells are inhibitory, with inhibitory postsynaptic
      potential considerably longer than those from FS interneurons. We use spike time
      response curve methods (STRC), expanding that technique to three-cell networks
      and giving two different ways in which the analysis of the three-cell network
      reduces to that of a two-cell network. We show that adding FS cells to a network
      of stellate cells can desynchronize the stellate cells, while adding them to a
      network of O-LM cells can synchronize the O-LM cells. These synchronization and
      desynchronization properties critically depend on I(h). The analysis of the
      deterministic system allows us to understand some effects of noise on the phase
      relationships in the stellate networks. The dynamic clamp experiments use
      biophysical stellate cells and in silico FS cells, with connections that mimic
      excitation or inhibition, the latter with decay times associated with FS cells or
      O-LM cells. The results obtained in the dynamic clamp experiments are in a good
      agreement with the analytical framework.

PMID- 16999574
TI  - Programmable logic construction kits for hyper-real-time neuronal modeling.
AB  - Programmable logic designs are presented that achieve exact integration of leaky
      integrate-and-fire soma and dynamical synapse neuronal models and incorporate
      spike-time dependent plasticity and axonal delays. Highly accurate numerical
      performance has been achieved by modifying simpler forward-Euler-based circuitry
      requiring minimal circuit allocation, which, as we show, behaves equivalently to
      exact integration. These designs have been implemented and simulated at the
      behavioral and physical device levels, demonstrating close agreement with both
      numerical and analytical results. By exploiting finely grained parallelism and
      single clock cycle numerical iteration, these designs achieve simulation speeds
      at least five orders of magnitude faster than the nervous system, termed here
      hyper-real-time operation, when deployed on commercially available field
      programmable gate array (FPGA) devices. Taken together, our designs form a
      programmable logic construction kit of commonly used neuronal model elements that
      supports the building of large and complex architectures of spiking neuron
      networks for real-time neuromorphic implementation, neurophysiological
      interfacing, or efficient parameter space investigations.

PMID- 16999575
TI  - Soft mixer assignment in a hierarchical generative model of natural scene
      statistics.
AB  - Gaussian scale mixture models offer a top-down description of signal generation
      that captures key bottom-up statistical characteristics of filter responses to
      images. However, the pattern of dependence among the filters for this class of
      models is prespecified. We propose a novel extension to the gaussian scale
      mixture model that learns the pattern of dependence from observed inputs and
      thereby induces a hierarchical representation of these inputs. Specifically, we
      propose that inputs are generated by gaussian variables (modeling local filter
      structure), multiplied by a mixer variable that is assigned probabilistically to
      each input from a set of possible mixers. We demonstrate inference of both
      components of the generative model, for synthesized data and for different
      classes of natural images, such as a generic ensemble and faces. For natural
      images, the mixer variable assignments show invariances resembling those of
      complex cells in visual cortex; the statistics of the gaussian components of the
      model are in accord with the outputs of divisive normalization models. We also
      show how our model helps interrelate a wide range of models of image statistics
      and cortical processing.

PMID- 16999576
TI  - The scaling of winner-takes-all accuracy with population size.
AB  - Empirical studies seem to support conflicting hypotheses with regard to the
      nature of the neural code. While some studies highlight the role of a distributed
      population code, others emphasize the possibility of a "single-best-cell"
      readout. One particularly interesting example of single-best-cell readout is
      provided by the winner-takes-all (WTA) approach. According to the WTA, every cell
      is characterized by one particular preferred stimulus, to which it responds
      maximally. The WTA estimate for the stimulus is defined as the preferred stimulus
      of the cell with the strongest response. From a theoretical point of view, not
      much is known about the efficiency of single-best-cell readout mechanisms, in
      contrast to the considerable existing theoretical knowledge on the efficiency of
      distributed population codes. In this work, we provide a basic theoretical
      framework for investigating single-best-cell readout mechanisms. We study the
      accuracy of the WTA readout. In particular, we are interested in how the WTA
      accuracy scales with the number of cells in the population. Using this framework,
      we show that for large neuronal populations, the WTA accuracy is dominated by the
      tail of the single-cell-response distribution. Furthermore, we find that although
      the WTA accuracy does improve when larger populations are considered, this
      improvement is extremely weak compared to other types of population codes. More
      precisely, we show that while the accuracy of a linear readout scales linearly
      with the population size, the accuracy of the WTA readout scales logarithmically
      with the number of cells in the population.

PMID- 16999577
TI  - An extended EM algorithm for joint feature extraction and classification in brain
      computer interfaces.
AB  - For many electroencephalogram (EEG)-based brain-computer interfaces (BCIs), a
      tedious and time-consuming training process is needed to set parameters. In BCI
      Competition 2005, reducing the training process was explicitly proposed as a
      task. Furthermore, an effective BCI system needs to be adaptive to dynamic
      variations of brain signals; that is, its parameters need to be adjusted online.
      In this article, we introduce an extended expectation maximization (EM)
      algorithm, where the extraction and classification of common spatial pattern
      (CSP) features are performed jointly and iteratively. In each iteration, the
      training data set is updated using all or part of the test data and the labels
      predicted in the previous iteration. Based on the updated training data set, the
      CSP features are reextracted and classified using a standard EM algorithm. Since
      the training data set is updated frequently, the initial training data set can be
      small (semi-supervised case) or null (unsupervised case). During the above
      iterations, the parameters of the Bayes classifier and the CSP transformation
      matrix are also updated concurrently. In online situations, we can still run the
      training process to adjust the system parameters using unlabeled data while a
      subject is using the BCI system. The effectiveness of the algorithm depends on
      the robustness of CSP feature to noise and iteration convergence, which are
      discussed in this article. Our proposed approach has been applied to data set IVa
      of BCI Competition 2005. The data analysis results show that we can obtain
      satisfying prediction accuracy using our algorithm in the semisupervised and
      unsupervised cases. The convergence of the algorithm and robustness of CSP
      feature are also demonstrated in our data analysis.

PMID- 16999578
TI  - On the consistency of Bayesian variable selection for high dimensional binary
      regression and classification.
AB  - Modern data mining and bioinformatics have presented an important playground for
      statistical learning techniques, where the number of input variables is possibly
      much larger than the sample size of the training data. In supervised learning,
      logistic regression or probit regression can be used to model a binary output and
      form perceptron classification rules based on Bayesian inference. We use a prior
      to select a limited number of candidate variables to enter the model, applying a
      popular method with selection indicators. We show that this approach can induce
      posterior estimates of the regression functions that are consistently estimating
      the truth, if the true regression model is sparse in the sense that the
      aggregated size of the regression coefficients are bounded. The estimated
      regression functions therefore can also produce consistent classifiers that are
      asymptotically optimal for predicting future binary outputs. These provide
      theoretical justifications for some recent empirical successes in microarray data
      analysis.

PMID- 16999579
TI  - A maximum likelihood approach to density estimation with semidefinite
      programming.
AB  - Density estimation plays an important and fundamental role in pattern
      recognition, machine learning, and statistics. In this article, we develop a
      parametric approach to univariate (or low-dimensional) density estimation based
      on semidefinite programming (SDP). Our density model is expressed as the product
      of a nonnegative polynomial and a base density such as normal distribution,
      exponential distribution, and uniform distribution. When the base density is
      specified, the maximum likelihood estimation of the polynomial is formulated as a
      variant of SDP that is solved in polynomial time with the interior point methods.
      Since the base density typically contains just one or two parameters, computation
      of the maximum likelihood estimate reduces to a one- or two-dimensional easy
      optimization problem with this use of SDP. Thus, the rigorous maximum likelihood
      estimate can be computed in our approach. Furthermore, such conditions as
      symmetry and unimodality of the density function can be easily handled within
      this framework. AIC is used to choose the best model. Through applications to
      several instances, we demonstrate flexibility of the model and performance of the
      proposed procedure. Combination with a mixture approach is also presented. The
      proposed approach has possible other applications beyond density estimation. This
      point is clarified through an application to the maximum likelihood estimation of
      the intensity function of a nonstationary Poisson process.

PMID- 16999580
TI  - Piecewise-linear neural networks and their relationship to rule extraction from
      data.
AB  - This article addresses the topic of extracting logical rules from data by means
      of artificial neural networks. The approach based on piecewise linear neural
      networks is revisited, which has already been used for the extraction of Boolean
      rules in the past, and it is shown that this approach can be important also for
      the extraction of fuzzy rules. Two important theoretical properties of piecewise
      linear neural networks are proved, allowing an elaboration of the basic ideas of
      the approach into several variants of an algorithm for the extraction of Boolean
      rules. That algorithm has already been used in two real-world applications.
      Finally, a connection to the extraction of rules of the Lukasiewicz logic is
      established, relying on recent results about rational McNaughton functions. Based
      on one of the constructive proofs of the McNaughton theorem, an algorithm is
      formulated that in principle allows extracting a particular kind of formulas of
      the Lukasiewicz predicate logic from piecewise-linear neural networks trained
      with rational data.

PMID- 16999581
TI  - Computation of madalines' sensitivity to input and weight perturbations.
AB  - The sensitivity of a neural network's output to its input and weight
      perturbations is an important measure for evaluating the network's performance.
      In this letter, we propose an approach to quantify the sensitivity of Madalines.
      The sensitivity is defined as the probability of output deviation due to input
      and weight perturbations with respect to overall input patterns. Based on the
      structural characteristics of Madalines, a bottom-up strategy is followed, along
      which the sensitivity of single neurons, that is, Adalines, is considered first
      and then the sensitivity of the entire Madaline network. By means of probability
      theory, an analytical formula is derived for the calculation of Adalines'
      sensitivity, and an algorithm is designed for the computation of Madalines'
      sensitivity. Computer simulations are run to verify the effectiveness of the
      formula and algorithm. The simulation results are in good agreement with the
      theoretical results.

PMID- 16999583
TI  - A cure for the Asian flu.

PMID- 16999584
TI  - Notes from a BWC Gadfly.

PMID- 16999585
TI  - Are regional hospital pharmacies prepared for public health emergencies?
AB  - INTRODUCTION: In the event of a major chemical, biological, radiological,
      nuclear, or explosive (CBRNE) attack or a natural disaster, large quantities of
      pharmaceuticals and medical supplies may be required with little or no warning.
      Pharmaceutical surge capacity for immediate response, before Strategic National
      Stockpile (SNS) supplies become available, remains a significant gap in emergency
      preparedness. To date, limited attempts have been made to assess collective
      regional hospital pharmaceutical response capabilities. In this project, we
      characterized the level of hospital pharmaceutical response preparedness in a
      major metropolitan region. METHODS: The Johns Hopkins Office of Critical Event
      Preparedness and Response (CEPAR) convened a collaborative partnership to assess
      hospital pharmaceutical response capabilities. A survey was developed to
      characterize pharmaceutical response preparedness to CBRNE threats. RESULTS: All
      22 acute care hospitals in the Maryland region were sent pharmaceutical response
      surveys, and responses were received from 86% (19/22). Within the past year, 84%
      (16/19) of hospitals had implemented an exercise with pharmacy participation.
      More than half of the hospitals expect to receive assistance from the SNS in 48
      hours or less. Seventy-four percent (14/19) of the hospitals reported an
      additional dedicated reserve supply for biological events, 74% (14/19) for
      chemical events, and 58% (11/19) for radiological events. CONCLUSION: Many
      hospitals in this metropolitan region have taken important steps toward enhancing
      pharmaceutical preparedness. However, hospitals generally remain underprepared
      for CBRNE threats and collectively have limited supplies of antibiotics to
      provide prophylaxis or treatment for hospital staff, their families, and patients
      in the event of a significant biological incident.

PMID- 16999586
TI  - Reducing mortality from anthrax bioterrorism: strategies for stockpiling and
      dispensing medical and pharmaceutical supplies.
AB  - A critical question in planning a response to bioterrorism is how antibiotics and
      medical supplies should be stockpiled and dispensed. The objective of this work
      was to evaluate the costs and benefits of alternative strategies for maintaining
      and dispensing local and regional inventories of antibiotics and medical supplies
      for responses to anthrax bioterrorism. We modeled the regional and local supply
      chain for antibiotics and medical supplies as well as local dispensing capacity.
      We found that mortality was highly dependent on the local dispensing capacity,
      the number of individuals requiring prophylaxis, adherence to prophylactic
      antibiotics, and delays in attack detection. For an attack exposing 250,000
      people and requiring the prophylaxis of 5 million people, expected mortality fell
      from 243,000 to 145,000 as the dispensing capacity increased from 14,000 to
      420,000 individuals per day. At low dispensing capacities (<14,000 individuals
      per day), nearly all exposed individuals died, regardless of the rate of
      adherence to prophylaxis, delays in attack detection, or availability of local
      inventories. No benefit was achieved by doubling local inventories at low
      dispensing capacities; however, at higher dispensing capacities, the cost
      effectiveness of doubling local inventories fell from 100,000 US dollars to
      20,000 US dollars/life year gained as the annual probability of an attack
      increased from 0.0002 to 0.001. We conclude that because of the reportedly rapid
      availability of regional inventories, the critical determinant of mortality
      following anthrax bioterrorism is local dispensing capacity. Bioterrorism
      preparedness efforts directed at improving local dispensing capacity are required
      before benefits can be reaped from enhancing local inventories.

PMID- 16999587
TI  - Trends in healthcare use in the New York City region following the Terrorist
      Attacks of 2001.
AB  - BACKGROUND: In 2001, terrorism led to emotional stress, disruptions in adherence
      to treatments and access to services, and exposure to environmental contaminants
      in New York City (NYC). METHODS: To describe healthcare use following the
      terrorist attacks of 2001, we examined insurance claims for January 2000 to March
      2002 among more than 2 million residents of the NYC region who were enrolled in
      the health plans of a large insurer, including overall use by care setting and
      use for selected conditions that may be associated with stress or other disaster
      consequences. For all enrollees and for those residing at varying distances from
      the World Trade Center (WTC), we compared observed use to expected use, based on
      comparable intervals in prior years and adjusted for seasonal and secular trends.
      RESULTS: Use declined across all care settings in the 3 weeks following September
      11. From October 1 to December 31, 2001, outpatient visits rose beyond expected
      both overall and for specific cardiovascular, gastrointestinal, and dermatologic
      conditions. Declines in overall mental health service use began immediately after
      September 11 and were sustained through March 2002. Changes in healthcare use
      were more marked among those residing within 10 miles of the WTC than those
      residing at greater distances. CONCLUSIONS: A transient decline in visits across
      all settings occurred immediately after September 11, followed by a sustained
      increase in demand for health care for conditions that may be associated with
      stress or other disaster consequences.

PMID- 16999588
TI  - The dual-use dilemma for the life sciences: perspectives, conundrums, and global
      solutions.
AB  - The term "dual-use" traditionally has been used to describe technologies that
      could have both civilian and military usage, but this term has at least three
      different dimensions that pose a dilemma for modern biology and its possible
      misuse for hostile purposes: (1) ostensibly civilian facilities that are in fact
      intended for military or terrorist bioweapons development and production; (2)
      equipment and agents that could be misappropriated and misused for biological
      weapons development and production; and (3) the generation and dissemination of
      scientific knowledge that could be misapplied for biological weapons development
      and production. These three different aspects of the "dual-use dilemma" are
      frequently confused--each demands a distinct approach within a "web of
      prevention" in order to reduce the future risk of bioterrorism and biowarfare.
      This article discusses the nature of the different perspectives and divergent
      approaches as a contribution to finding a scientifically acceptable global
      solution to the problem posed by the dual-use dilemma. We propose that: (1)
      facilities that are intended for bioweapons development and production should be
      primarily prevented by a strengthened Biological and Toxin Weapons Convention
      (BTWC) effectively implemented in all nation states, one that includes provisions
      for adequate transparency to improve confidence and a mechanism for thorough
      inspections when there is sufficient cause, and enhanced law enforcement
      activities involving international cooperation and sharing of critical
      intelligence information; (2) potentially dual-use equipment and agents should be
      available to legitimate users for peaceful purposes, but strengthened national
      biosafety and physical and personnel biosecurity controls in all nations together
      with effective export controls should be implemented to limit the potential for
      the misappropriation of such equipment and materials; and (3) information should
      be openly accessible by the global scientific community, but a culture of
      responsible conduct involving the breadth of the international life sciences
      communities should be adopted to protect the ongoing revolution in the life
      sciences from being hijacked for hostile misuse of the knowledge generated and
      communicated by life scientists.

PMID- 16999590
TI  - Use of the internet to enhance infectious disease surveillance and outbreak
      investigation.
AB  - Modernization of electronic communication systems to facilitate infectious
      disease surveillance and outbreak investigation became a priority after the 2001
      anthrax attacks. However, the extent to which communicable disease investigators
      are using web-based information resources, e-mail notifications, or secure
      information exchange systems to facilitate surveillance is unknown. To address
      this question, we conducted a survey in 2004 of state and local communicable
      disease investigators responsible for infectious disease surveillance and
      outbreak investigation in three states. The majority (70.7%) of the 297
      respondents accessed the Internet for information regarding infectious disease
      surveillance and outbreaks at least weekly. Most (74%) respondents who searched
      for information from the Centers for Disease Control and Prevention (CDC) website
      reported that they found what they were looking for 75-100% of the time, compared
      with 54% who found the information from their state health department websites 75
      100% of the time. One-third of respondents read e-mail notifications regarding
      outbreaks under investigation in their state less frequently than monthly; 34% of
      those enrolled in CDC's Epidemic Information Exchange (Epi-X) read e-mail
      notifications of new reports less frequently than monthly. Forty-seven (18%)
      respondents read ProMED-mail at least monthly, while 46% indicated they had never
      consulted MEDLINE/PubMed. Some progress has been made in use of the Internet to
      facilitate communication in infectious disease surveillance and outbreak
      investigation. Addressing barriers to access and usability of new information
      systems in conjunction with training and technical support could enhance
      infectious disease surveillance and timely investigation of outbreaks and
      bioterrorism events.

PMID- 16999589
TI  - Bioterrorism with zoonotic disease: public health preparedness lessons from a
      multiagency exercise.
AB  - Responding to agricultural bioterrorism with pathogenic agents that are
      communicable from animals to humans (zoonotic diseases) requires effective
      coordination of many organizations, both inside and outside of government. Action
      must be simultaneously taken to address public health concerns, respond to the
      agricultural dimensions of the event, and carry out the necessary law enforcement
      investigation. As part of a project focused on examining public health
      preparedness in Georgia, an exercise was carried out in July 2005 examining the
      intentional introduction of avian influenza (H5N1) in commercial poultry
      operations. The attack scenario, which was written to occur during an already
      severe human influenza season, enabled exploration of a range of issues
      associated with public health preparedness for major disease outbreaks including
      pandemic influenza, coordination of a multiagency response operation at multiple
      levels of government, and effective management of interdisciplinary response
      activities. The exercise is described and broader policy lessons regarding
      preparedness planning are discussed.

PMID- 16999591
TI  - Physician assistants and bioterrorism preparedness.
AB  - Despite the resources dedicated since 2001 to training health providers in
      emergency and bioterrorism preparedness and response, the literature on the
      participation of physician assistants (PAs) is very limited. The purpose of this
      pilot study was to explore the training level and experiences of PAs in the
      diagnosis and treatment of chemical, biological, radiological, nuclear, and
      explosive agents that could be used in a bioterrorism attack. The study
      population consisted of licensed PAs in 37 northern Texas counties. Data were
      collected through mailed and web-based surveys. Response rate was 36%. More than
      half of the respondents (58.6%) had not participated in bioterrorism preparedness
      and response training. Results also indicated that the level of training has not
      increased since September 11, 2001. However, most respondents were receptive to
      the idea of participating in both preparedness training and response efforts. It
      is recommended that state agencies increase training opportunities for PAs in
      bioterrorism preparedness and response.

PMID- 16999592
TI  - Risky business: planning for pandemic flu.

PMID- 16999593
TI  - Disease, disaster, and democracy: the public's stake in health emergency
      planning.

PMID- 16999594
TI  - Comments from the Center for Biosecurity of UPMC on the National Strategy for
      Pandemic Influenza: Implementation Plan.

PMID- 16999595
TI  - Recombinant antibodies: from the laboratory to the clinic.
AB  - The development of recombinant antibodies has facilitated the exploitation of the
      Ab-Ag interaction specificity for targeted therapies. A fully human antibody,
      with custom integrated designs, can be obtained in one-third the time, compared
      to development of antibodies by hybridoma technology. Recombinant antibodies can
      be tailored for specific applications, "armed" with cytotoxic agents in a
      controllable fashion, and used for extracellular and intracellular targeting.
      Multitargeted and combination therapies are rapidly evolving for the treatment of
      cancer. Antibody therapeutics, costly to develop and produce, have proven
      beneficial in the clinic.

PMID- 16999596
TI  - Regional yttrium-90 microsphere treatment of surgically unresectable and
      chemotherapy-refractory metastatic liver carcinoma.
AB  - PURPOSE: The aim of this prospective study was to assess the safety and tumor
      response of intra-arterial Y-90 microspheres for the treatment of surgically
      unresectable and chemotherapy-refractory liver metastases. MATERIALS AND METHODS:
      Forty-six (46) patients with metastatic cancer to the liver from various solid
      tumors, with tumor progression despite polychemotherapy, were included. All
      patients had baseline computed tomography (CT), 18-Fluoro-2-deoxy-D-glucose
      positron emission tomography (F-18 FDG-PET), hepatic angiography, and intra
      arterial Tc-99m macroaggregated albumin (MAA) scan for the assessment of
      extrahepatic aberrant perfusion and lung shunting fraction. Twenty-seven (27) and
      19 patients were treated with Y-90 glass- or resin-based microspheres (but not
      both), respectively, on a lobar basis and were monitored over 3 months after last
      treatment using dedicated attenuation corrected PET. For each patient, regions of
      interest (ROIs) were drawn along the liver edge to measure total liver standard
      uptake value (SUV) on axial images covering the entire liver for comparing pre-
      and post-treatment total liver SUV change. RESULTS: There was a significant
      decrement in total liver SUV after treatment by either glass- or resin-based
      microspheres (p = 0.0013 and 0.028, respectively). There was no significant
      difference in the amplitudes of the mean percentage reduction of tumor metabolism
      between these two agents (20% +/- 25% vs. 10% +/- 30% for glass- vs. resin-based
      microspheres; p = 0.38). None of the patients in the glass-based group developed
      complications, whereas 3 patients had complications related to hyperbilirubinemia
      (1 transient and 2 permanent) in the resin-based group. CONCLUSIONS: Results
      suggest that there is significant mean reduction of hepatic metastatic tumor load
      (metabolism), as evaluated objectively by PET after Y-90 microsphere, for the
      treatment of unresectable metastatic disease to the liver. The Y-90 therapy
      provides encouraging and safe results by arresting the progression of metastatic
      cancer to the liver with decreasing tumor metabolism.

PMID- 16999597
TI  - Induction of G2 arrest and apoptosis of raji cells by continuous low-dose beta
      irradiation with 188Re-perrhenate.
AB  - Continuous irradiation with exponentially reducing beta-rays induces cell death,
      known as apoptosis. The aim of this study was to investigate the G2 arrest and
      apoptosis caused by the beta-ray emitted by the radioisotope (188)Re. Doses of
      0.4 Gy (3.7 MBq), 4 Gy (37 MBq), and 40 Gy (370 MBq), were added to Blymphoma
      Raji cells, and cell viability, apoptosis, and DNA cell-cycle changes were
      assayed. (188)Re showed time- and dose-dependent effects on cell viability and on
      cell apoptosis and necrosis. At a (188)Re dose of 0.4 Gy, G(2) cell-cycle arrest
      was observed after 16 hours, and 4,6-diamidino-2-phenylindole (DAPI) staining
      indicated a slow, time-dependent increase in apoptotic bodies. At a (188)Re dose
      of 40 Gy, DNA fragmentation was observed at 2 hours, indicative of early damage
      in the nucleus. In summary, our results showed that continuous irradiation with
      low-dose beta-rays induced G(2) arrest and progressive apoptosis, which may be
      characteristic mechanisms of radionuclide therapy.

PMID- 16999598
TI  - Cytotoxicity of a novel fibroblast growth factor receptor targeted immunotoxin on
      a human ovarian teratocarcinoma cell line.
AB  - Basic fibroblast growth factor (bFGF) is an important tumor-associated growth
      factor that contributes to proliferation and angiogenesis of tumor. The high
      affinity receptor for bFGF, fibroblast growth factor receptor (FGFR), is found to
      be overexpressed in a number of tumor cells. For the purpose of exploring the
      significance of bFGF/FGFR in tumor-targeted therapy, a recombinant immunotoxin
      contained the N-terminal 389 residues of diphtheria toxin (DT), and the full
      length of human bFGF was designed, expressed, and purified. The bioactivity of
      the product was evaluated by testing the cytotoxicity on PA-1 cells (a human
      ovarian teratocarcinoma cell line with high-level expression of FGFR) in vitro.
      The immunotoxin showed a significant cytotoxicity on PA-1 cells (IC(50) 8 - 9
      ng/mL), and this effect could be antagonized by equine diphtheria antitoxin
      (DAT), bFGF, anti-bFGF monoclonal antibody (MAb), and anti- FGFR polyclonal
      antibody (PAb), respectively. Additionally, Chinese hamster ovary (CHO) cells and
      Hep-2 cells (a human epidermoid laryngocarcinoma cell line) with low expression
      of FGFR were tested to be resistant to the immunotoxin. The results indicated
      that FGFR might be an effective target for tumor therapy, and bFGF-mediated
      immunotoxin could be a potential candidate in the treatment of cancer.

PMID- 16999599
TI  - Particle-mediated cytokine gene therapy leads to antitumor and antimetastatic
      effects in mouse carcinoma models.
AB  - BACKGROUND: We investigated the effects of continuous cancer gene therapy
      including (antigen-presenting cell) (APC) engineering and local stimulation of
      the immune system. MATERIALS AND METHODS: Lewis lung carcinomas and B16
      melanomas, intradermally established on C57/Bl6 mice, were shot using a gene gun
      every 4th day with a combination of plasmids. The first therapy group received
      plasmids coding the genes for interleukin (IL)-12 and IL-2. The second therapy
      group was treated with plasmids coding for B7.1 interferon-gamma (IFN-gamma)/IL
      12 alternated by a plasmid coding IL-2. Control were mice without any therapy or
      treatment with the empty plasmid. RESULTS: Gene therapy led to reduced tumor
      sizes in the therapy groups of both models (significant for the Lewis lung
      carcinoma). We found an enhanced survival and reduced tumor growth rate in the
      therapy groups; however, the effects were not significant. IL- 12/IL-2 therapy
      was more effective, compared to B7.1/IFN-gamma/IL-12 and IL-2. Cytokine gene
      transfer let to a significantly lower metastasis rate in Lewis lung carcinoma.
      CONCLUSIONS: Continuous particle-mediated gene transfer is easy to handle and
      shows good results. Gene therapy combining the genes coding for IL-12 and IL-2
      was superior to additional IFN-gamma/B7.1. APC engineering does not appear to be
      sufficient in these poorly antigenic tumors.

PMID- 16999600
TI  - Evaluation of the cell death pathway and apoptosis-stunning effect relationship
      after low- and high-dose I-131 administrations in rat thyroid tissue.
AB  - OBJECTIVES: This study had two aims; (1) to describe the cell death pathway
      (apoptosis or necrosis) induced by a low and high dose of radioiodine (I-131) in
      rat thyroid tissue in in vivo conditions and (2) to determine the role of
      apoptosis in the development of "stunning effect" in the thyroid tissue with low
      and high doses of I-131 application. DESIGN: The experimental group consisted of
      18 rats; low and high I- 131 doses with a 1-week interval were administered to
      this group. At first, low doses were injected intraperitoneally (i.p.) (net
      injected dose was 51.54 +/- 8.6 microCi). After 1 week of the low-dose injection,
      high doses were also injected (net injected dose was 934.9 +/- 211.8 microCi).
      Thyroidal I-131 uptakes for both low- and high-dose applications were calculated
      by using a gamma camera after 24 hours of injections. Immediately after the
      uptake calculation, thyroid tissues were resected. A control group of 10 rats was
      also included in the study; in this group, I-131 was not administered. Thyroid
      tissues of this group rats were also resected. DNA was extracted from thyroid
      tissues, and damage was examined with the "DNA ladder by agaroz gel
      electrophoresis." RESULTS: Thyroidal I-131 uptakes were calculated as 11.3% +/-
      3.6% and 9.8% +/- 5.3% at the 24th hour after low- and high-dose I-131
      applications, respectively. When the low- and high-dose uptake values were
      compared for each rat; a significant relationship was not found between thyroidal
      uptakes and injected low and high doses of I-131. When the chromosome images were
      examined, there was healthy DNA appearance in 1 rat; in 4 rats, only necrotic
      hyperfragmentations were observed; in 9 rats, both apoptotic specific
      fragmentations and necrotic hyperfragmentations were observed; and in 4 rats,
      apoptosis, necrosis, and healthy DNA appearances were seen together. In none of
      the rats, specific fragmentations concordant only with apoptosis was found. When
      the thyroidal uptake alterations were taken into consideration, significant
      difference was not found between first and second uptake calculations (p = 0.28).
      No significant relationship was also observed between thyroidal uptake
      alterations and apoptosis-necrosis-healthy DNA findings. Additionally, when we
      take into consideration the DNA results of only 13 of the rats that had reduced
      thyroidal uptake, a significant relationship could also not be observed between
      reduced uptake and apoptotic, necrotic, or healthy tissue findings.
      Interestingly, apoptotic and necrotic tissue or only necrotic, tissue findings
      were observed in the other 5 rats which had increased thyroidal uptake.
      CONCLUSIONS: Following I-131 administration, two types of cell death--both
      apoptosis and necrosis findings--have been observed in most of the rats. We think
      that the decreased uptake values are because of the probable stunning effect in
      thyroid tissue. We also investigated whether the stunning effect is related to
      apoptosis. According to our results, it can be concluded that the stunning effect
      is not related to tissue damage, cell decrease, or cell death. Alternatively, we
      think that this can be related to a radiation-induced reduction of iodine
      uptake/metabolism or a modified iodine transport mechanism. For further in vivo
      studies, this experimental model using normal rat thyroid tissue may be useful in
      investigating the cell death pathways induced by I-131 and its probable roles in
      the development of the stunning phenomenon.

PMID- 16999601
TI  - Correlations of total pelvic spongiosa volume with both anthropometric parameters
      and computed tomography-based skeletal size measurements.
AB  - Patient-specific dosimetry within the field of molecular radiotherapy continues
      to pose a challenge owing to the difficulty in predicting marrow toxicity. This
      study examined the correlation between total pelvic spongiosa volume (TPSV) and
      independent variables, which include both readily measured or calculated
      anthropometric parameters (AP), and image-based skeletal measurements requiring
      computed tomography (CT) images or skeletal radiographs. Fourteen (14) patients
      (5 male and 9 female) undergoing total hip arthroplasty (THA) were subjected to
      modified pelvic CT scans. These scans were utilized to estimate TPSV, which was
      comprised of the volumes of spongiosa within the L5 vertebra, os coxae, sacrum,
      and both proximal femurs. The APs investigated included total body height (TBH),
      total body mass (TBM), body mass index (BMI), body surface area (BSA), maximum
      effective mass (MEM), lean body mass (LBM), and fat-free mass (FFM). Skeletal
      measurements were also obtained from the CT images of the pelvic region.
      Correlation coefficients (r) were obtained for TPSV and each set of APs as well
      as each set of skeletal measurements. Total body height (r = 0. 80) and os coxae
      height (r = 0.83) had the highest correlation coefficients of all the APS and
      skeletal measurements, respectively. FFM (r = 0.50), LBM (r = 0.42), TBM (r =
      0.11), and BSA (r = 0.11) did not correlate well with TPSV, which accounts for
      approximately 45% of total spongiosa seen throughout the skeleton at sites
      associated with active bone marrow. Skeletal height measurements appear to have a
      much higher correlation with TPSV than either their corresponding skeletal width
      measurements or parameters that are a function of an individual's TBM.

PMID- 16999602
TI  - In vitro screening for synergism of high-linear energy transfer 213Bi
      radiotherapy with other therapeutic agents for the treatment of B-cell chronic
      lymphocytic leukemia.
AB  - BACKGROUND: External beam radiotherapy and beta-radioimmunotherapy (RIT) are
      effective treatments for lymphoid malignancies. The development of RIT with alpha
      emitters is attractive, owing to the high (LET) nature and short path length of
      alpha particles allowing for higher tumor cell kill and lower toxicity to healthy
      tissues. OBJECTIVES: The aim of this study was to assess the response of B-Cell
      chronic lymphocytic leukemia (B-CLL) cells in vitro after treatment with
      chemotherapy (cisplatin, fludarabine, doxorubicin, or vincristine) or other
      pharmaceuticals (colchicine, simvastatin, or cyclosporin A) in combination with
      (60)Co-gamma or (213)Bi-alpha-irradiation. METHODS: (213)Bi was eluted from a
      (225)Ac generator. Apoptosis was scored by flow cytometric analysis of the cells
      stained with Annexin-V and 7 amino actinomycin D. Metabolic activity was assessed
      by a MTT assay. RESULTS: The response induced by alpha- irradiation is
      systematically higher than the response induced by gamma-irradiation. The
      combination of drug treatment with alpha-irradiation induced a systematic, higher
      response, compared to treatment with drugs alone, even for the highest
      concentrations used. For all the drugs used in this study, synergism or
      additivity was demonstrated for the combination of drugs and radiotherapy with a
      stronger effect for alpha-particles. CONCLUSIONS: The results of this in vitro
      study highlight a potential benefit of alpha-irradiation in combination with the
      drugs considered in this study.

PMID- 16999603
TI  - Abstracts from the Eleventh Conference on Cancer Therapy with Antibodies and
      Immunoconjugates. October 12-14, 2006. Parsippany, New Jersey, USA.

PMID- 16999607
TI  - Progressive increase of lithotripter output produces better in-vivo stone
      comminution.
AB  - BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) has become a first-line
      intervention for treatment of nephrolithiasis. However, few studies have examined
      the effects of modifications in the method of shockwave energy administration on
      comminution efficiency. We propose that a gradual increase in output voltage will
      produce superior stone fragmentation in comparison with a constant or a
      decreasing output voltage by optimizing the stress wave and cavitation erosion
      forces on renal calculi. MATERIALS AND METHODS: BegoStone phantoms were implanted
      in the renal pelvis of 11 pigs that underwent SWL at a pulse repetition rate of 1
      Hz. Animals in the increasing strategy group (N = 4) were subjected to 18, 20,
      and 22 kV for 600, 600, and 800 shocks, respectively. The second group (N = 4)
      received a decreasing strategy of 22, 20, and 18 kV for 800, 600, and 600 shocks,
      respectively. The third group (N = 3) received all 2000 shocks at 20 kV,
      mimicking the clinical protocol. RESULTS: A progressively decreasing strategy and
      constant output voltage produced a mean comminution efficiency, or percentage of
      stone fragments <2 mm, of 89.0% +/- 3.3% and 87.6% +/- 1.7%, respectively. The
      mean comminution efficiency was improved to 96.5% +/- 1.4% by using the
      increasing strategy (P = 0.01). CONCLUSIONS: A progressive increase in
      lithotripter output voltage during SWL can produce greater stone fragmentation
      than protocols employing constant or decreasing output voltage.

PMID- 16999608
TI  - Reducing shock number dramatically decreases lesion size in a juvenile kidney
      model.
AB  - BACKGROUND AND PURPOSE: Adult stone patients are treated with several thousand
      lithotripter shockwaves (SWs) in order to pulverize a kidney stone. This typical
      clinical dose assures that the stone will be fractured completely. However, this
      same dose induces damage to the kidney, especially pediatric-size kidneys. If
      increasing SW number is known to increase renal injury and functional impairment,
      will reducing SW number below typical treatment levels significantly decrease
      kidney damage and hemodynamic changes? MATERIALS AND METHODS: To address this
      question, one kidney in each of nine juvenile pigs (6-7 weeks old) was treated
      with 1000 SWs at 24 kV directed at a lower-pole calix with an unmodified HM-3
      lithotripter. Parenchymal-lesion size was determined by sectioning the entire
      kidney and quantitating the amount of hemorrhage in each slice. Renal function
      was determined before and after SW treatment by inulin clearance,
      paraaminohippurate (PAH) extraction, and PAH clearance. The resulting morphologic
      and functional changes were then compared with those of kidneys that had been
      treated with a typical clinical dose of 2000 SWs (data previously published; J Am
      Soc Nephrol 2000;11:310). Eleven pigs were utilized as sham-treated controls.
      RESULTS: Limiting SW number to 1000 significantly reduced the size of the lesion
      (by 95%) and reduced the degree of functional change (glomerular filtration rate
      by 38%, PAH extraction by 73%, renal plasma flow by 46%) compared with kidneys
      receiving 2000 SWs (an adult dose). CONCLUSIONS: These data support the idea that
      SW number should be reduced to the lowest number that fractures kidney stones in
      order to minimize renal injury and functional impairment.

PMID- 16999609
TI  - Controversial cases in endourology.

PMID- 16999610
TI  - Impacted upper-ureteral calculi >1 cm: blind access and totally tubeless
      percutaneous antegrade removal or retrograde approach?
AB  - PURPOSE: To compare blind access and totally tubeless percutaneous antegrade
      removal and pneumatic transurethral ureterolithotripsy for the management of
      impacted upper-ureteral calculi >1 cm. PATIENTS AND METHODS: Seventy patients (41
      male, 29 female) with impacted upper-ureteral calculi >1 cm were selected in
      randomized order for pneumatic transurethral ureterolithotripsy (35 patients) or
      blind access and totally tubeless percutaneous nephrolithotomy (PCNL) (35
      patients). Ultrasonography and intravenous urography were performed for all
      patients before surgery. After operation, plain films and ultrasonography were
      done. RESULTS: In the PCNL group, blind access was achieved from the lumbar notch
      area in all 35 patients, but in 3 patients, the exposure was not optimal for
      approaching the ureteropelvic junction (UPJ). So we injected contrast material
      into the collecting system, and, under fluoroscopic control, another access was
      achieved. In 33 patients (94.3%), intact removal of the stones was performed. In
      the other two patients, we fragmented the stones with the Swiss Lithoclast by an
      antegrade approach. The success rate thus was 100%. The mean operative time was
      38 minutes (range 25-48 minutes). In the transurethral lithotripsy group, 12
      stones (34.2%) migrated upward to the pelvis of kidney, and 5 stones (14.2%)
      fragmented incompletely. In these cases, a double- J stent was inserted, and SWL
      was performed. In follow-up, plain films and ultrasonography showed complete
      clearance in these patients. Eighteen calculi (51.4%) fragmented completely with
      the Lithoclast. The mean operative time in this group was 34 minutes (range 20-58
      minutes). CONCLUSION: In the presence of moderate to severe hydronephrosis, blind
      access and totally tubeless PCNL is an effective option for large, impacted upper
      ureteral calculi. Flexible ureteroscopy with laser lithotripsy is expensive and
      not readily available. Pneumatic transurethral ureterolithotripsy has a back
      pressure effect and pushes back the calculi to the kidney. Thus, this procedure
      does not have satisfactory results in the management of these calculi.

PMID- 16999611
TI  - Guidewire-assisted infundibular tilt: a technique for access into another calix
      during percutaneous nephrolithotomy.
AB  - Sometimes, during percutaneous nephrolithotomy, a stone fragment migrates into a
      parallel calix, necessitating a separate puncture. We describe a simple technique
      for removing such fragments. This technique is especially useful for patients who
      have moderate to severe hydronephrosis where the intercaliceal parenchyma is
      thin.

PMID- 16999612
TI  - Safe and novel technique for peritoneal access in urologic laparoscopy without
      prior insufflation.
AB  - BACKGROUND AND PURPOSE: Access to the peritoneum for transperitoneal laparoscopic
      surgery can be achieved using a variety of techniques, each of which has
      advantages and disadvantages as well as risks of complications. The endoscopic
      threaded imaging port (EndoTIP) is a metal, reusable, threaded visual-access
      cannula that is inserted by rotational rather than axial force. When the
      technique was described initially, capnoperitoneum was obtained prior to trocar
      insertion. We describe the results of our series using the EndoTIP port without
      prior capnoperitoneum. PATIENTS AND METHODS: All 165 patients who underwent
      urologic transperitoneal laparoscopic procedures using the EndoTIP performed by a
      single surgeon from October 2001 through June 2005 were reviewed. Twentyfive
      patients were morbidly obese, and 32 had had previous abdominal surgical
      procedures. All data regarding patient demographics, details of the procedures,
      and outcomes were obtained from a database developed for prospective data
      collection at our institution. RESULTS: There were no complications associated
      with peritoneal access or trocar insertion. The average time required to obtain
      capnoperitoneum was <1 minute. CONCLUSIONS: Insertion of the EndoTIP port without
      prior capnoperitoneum is a safe, quick, and reliable method for peritoneal access
      in laparoscopic surgery. By avoiding blind punctures of the abdominal cavity, the
      risk of complications during access is minimized. We believe this technique
      should be considered in preference to techniques where trocars are inserted
      blindly.

PMID- 16999613
TI  - Laparoscopic and open retroperitoneal lymph-node dissection for clinical stage I
      nonseminomatous germ-cell testis tumors.
AB  - BACKGROUND AND PURPOSE: Laparoscopic retroperitoneal lymph node dissection (L
      RPLND) has been reported as efficacious for staging of the retroperitoneum in
      patients with stage I nonseminomatous germ-cell testis tumors (NSGCT). However,
      reports are limited to a few centers, and this procedure has yet to be widely
      accepted as an alternative to open retroperitoneal lymph node dissection (O
      RPLND). Thus, we compared our contemporary open and laparoscopic experience with
      RPLND. PATIENTS AND METHODS: A retrospective chart review identified 28 patients
      who underwent either open (N = 6) or laparoscopic (N = 22) RPLND for clinical
      stage I NSGCT since 2000. Each patient received the appropriate modified template
      dissection. Perioperative demographic data, histologic nodal status, and
      recurrence data were evaluated. The mean follow-up was similar in the two groups.
      RESULTS: The mean operative time was not significantly different (313 minutes for
      L-RPLND v 284 minutes for O-RPLND). However, L-RPLND did have a significantly
      shorter hospitalization (1.2 v 8.5 days). Significantly more lymph nodes were
      removed with O-LPLND than with L-RPLND (mean 33 v 17). There was a single
      recurrence outside the modified template after both L-RPLND and O-RPLND and one
      within-the-template recurrence in the O-RPLND group. CONCLUSIONS: The L-RPLND is
      associated with less blood loss and a shorter hospital stay than O-RPLND, whereas
      the lymph-node yield of O-RPLND is greater. However, during the critical early
      follow-up period, the oncologic effectiveness and morbidity of L-RPLND for
      clinical stage I NSGCT appears similar to that of O-RPLND.

PMID- 16999614
TI  - Laparoscopic ureteroneocystostomy with vesicopsoas hitch: nonrefluxing ureteral
      reimplantation using cystoscopy-assisted submucosal tunneling.
AB  - PURPOSE: We described laparoscopic nonrefluxing ureteral reimplantation with a
      psoas hitch using a submucosal tunneling technique combined with cystoscopy.
      PATIENTS AND METHODS: We performed this operation on two female patients. The
      first patient had a right lower-ureteral stricture after a laparoscopy-assisted
      vaginal hysterectomy, and the second patient had a left distal-ureteral stricture
      after a left laparoscopic oophorectomy, which was performed for endometriosis. We
      performed laparoscopic intravesical ureteral reimplantations with a psoas hitch
      using submucosal tunneling after a submucosal injection of normal saline was
      provided under cystoscopy. RESULTS: The operative times were 325 and 280 minutes,
      respectively. The estimated blood loss was 300 mL in the first case and 120 mL in
      the second. The hospital stays were 5 and 3 days, respectively. There were no
      postoperative complications. Follow-up voiding cystourethrography and intravenous
      urography demonstrated normal compliance and function of the kidneys and ureters
      with no vesicoureteral reflux. CONCLUSIONS: Laparoscopic intravesical
      nonrefluxing ureteroneocystostomy with a psoas hitch is a safe and feasible
      procedure. Cystoscopic submucosal injection of normal saline during submucosal
      tunneling is beneficial.

PMID- 16999615
TI  - Case report: laparoscopic heminephrectomy in a horseshoe kidney using bipolar
      energy.
AB  - Aberrant vasculature, functional parenchyma in the isthmus, and abnormal location
      are all unique features of horseshoe kidney that present technical challenges to
      laparoscopic management of disease. A 52-year-old man presented with a large
      renal calculus in a poorly functioning left moiety of a horseshoe kidney and
      underwent laparoscopic heminephrectomy. The ismthus, which had 2.5 to 3.0 cm of
      functioning parenchyma, was divided using the PlasmaKinetic Superpulse Generator
      (Gyrus). No additional hemostatic measure was required. The total operative time
      was 140 minutes with an estimated blood loss of 160 mL. At follow-up, the right
      moiety and remaining isthmus exhibited normal function with no extravasation.

PMID- 16999616
TI  - Case report: laparoscopic Boari flap.
AB  - A Boari flap may be required to bridge long defects of the middle and lower
      ureter to the bladder. Laparoscopic construction of a Boari flap was performed in
      a patient with a ureteral stricture secondary to iatrogenic injury. The salient
      steps performed were spatulation of the transected ureteral end, fashioning of a
      Boari flap from the bladder, end-to-side anastomosis of the ureter to the flap,
      placement of a stent with the aid of a suction cannula, and closure of the flap
      over the stent. A Boari flap can be accomplished laparoscopically with minimal
      morbidity.

PMID- 16999617
TI  - High body mass index in muscular patients and flank position are risk factors for
      rhabdomyolysis: case report after laparoscopic live-donor nephrectomy.
AB  - BACKGROUND AND PURPOSE: Rhabdomyolysis is well known after traumatic crush
      injuries or ischemia involving muscles. Postoperatively, it most likely is
      secondary to surgical positioning and patient muscle mass. We report a case after
      laparoscopic live-donor nephrectomy. CASE REPORT: A muscular 35-year-old man
      underwent elective left laparoscopic live-donor nephrectomy in a 70 degrees flank
      position with four ports. He was in the right-side lying position with hip
      flexion (flank position) for approximately 4 hours. A kidney bridge had been
      placed between the iliac crest and the rib cage. Postoperatively, the patient had
      light-pinkish urine and low urine output. There was marked induration of the
      buttocks and significant pedal and scrotal edema. With judicious use of
      alkalinization and diuretics, the patient did not require dialysis, and renal
      function returned to base level by postoperative day 20. The recipient of the
      kidney had a normal postoperative course. CONCLUSION: Rhabdomyolysis is a
      syndrome of muscle necrosis and release of intracellular components into the
      circulation. Acute renal failure secondary to myoglobinuria is a common
      complication. We currently use little flexion of the table during donor
      nephrectomy and bring the table to a neutral position immediately after kidney
      retrieval. Postoperatively, one needs a high index of suspicion for
      rhabdomyolysis to avoid or at least promptly recognize this rare but potentially
      serious condition after any operation lasting >or=4 hours.

PMID- 16999618
TI  - Fast and safe closing of urethra during laparoscopic radical cystectomy.
AB  - PURPOSE: To present a simple alternative technique to close the membranous
      urethra during laparoscopic radical cystectomy. PATIENTS AND METHODS: A series of
      18 laparoscopy-assisted cystectomies were performed in our institute from
      November 2002 to May 2005. In order to prevent neoplastic-cell spillage, in 14 of
      these patients, the membranous urethra was closed with Hem-o-lok clips after
      careful dissection of the urethra and withdrawal of the bladder catheter.
      RESULTS: In all cases, one or two Hem-o-lok clips were easily, safely, and
      quickly positioned. The remaining length of the membranous urethra was sufficient
      for anastomosis with the neobladder if appropriate. In follow-up (mean 14
      months), no local recurrence has been recorded. CONCLUSION: The closing of the
      membranous urethra with Hem-o-lok clips during laparoscopy-assisted cystectomy is
      in our experience a simple, fast, safe, and effective alternative that should be
      considered when laparoscopic radical cystectomy is performed.

PMID- 16999619
TI  - Novel technique to prevent lymphocele recurrence after laparoscopic lymphocele
      fenestration in renal transplant patients.
AB  - PURPOSE: To describe the use of nonabsorbable polymer ligating (NPL) clips to
      prevent recurrence after laparoscopic lymphocele fenestration and to determine
      the efficacy and safety of this treatment in renal-transplant patients at our
      center. PATIENTS AND METHODS: From December 2000 to October 2005, nine patients
      with a mean age of 38.5 years (range 26-54 years) and symptomatic lymphoceles
      were treated laparoscopically among 144 renal-transplant patients. The overall
      incidence of symptomatic lymphocele was 6.2% (9/144). The mean time from
      transplantation to diagnosis was 55.5 days (range 20-98 days). Patient and
      lymphocele characteristics, complications, recurrence rate, and outcomes of this
      procedure were analyzed retrospectively. RESULTS: Laparoscopic treatment was
      successful in eight patients; the other was converted to open surgery. One
      patient sustained an allograft-ureteral injury. The mean operative time was 90.7
      minutes (range 75-120 minutes), and the mean postoperative stay was 4.1 days
      (range 1-7 days). Lymphocele recurrence was found in the first two patients after
      laparoscopic surgery without NPL clips. With a mean follow-up of 42.3 months
      (range 31-51 months), no recurrence was observed in patients in whom NPL clips
      were used to maintain the patency of the peritoneal window. No late laparoscopy
      related complications occurred. CONCLUSION: Laparoscopic lymphocele fenestration
      with NPL clips is a safe, technically easy, and efficacious procedure for the
      treatment of symptomatic lymphoceles after renal transplantion.

PMID- 16999620
TI  - Case reports: ureteroscopic removal of eroded staples in two patients with
      history of laparoscopic surgery.
AB  - Complications from laparoscopically placed staples are rare. We present two
      patients with ureteral obstruction secondary to eroded staples. Each patient had
      a remote history of laparoscopic abdominal or pelvic surgery and was treated with
      endoscopic removal and short-term ureteral stenting. The clinical presentation
      and management are discussed.

PMID- 16999621
TI  - Minimally invasive treatment of ureteropelvic junction obstruction: optimizing
      outcomes with concomitant cost reduction.
AB  - With the seemingly exponential increase in the use of minimally invasive
      techniques in urology, cost-benefit comparisons will continue to play a major
      part in establishing services and in improving those that already exist. The
      management of ureteropelvic junction obstruction is a focus of significant
      attention. An effective way of optimizing the economy of management is to
      understand the implications in terms of the success of each mode of treatment.
      Subsequently, costing models should be developed and applied in large-scale
      multicenter studies with the aid of health economists. The long-term benefits can
      then be assessed by also including patient's perceived quality of life. Economic
      assessment will not be enough to promote cost-effective practices. The take-up of
      any techniques will always be influenced not only by patient preference and
      surgeon expertise but also, perhaps ironically, by the way hospitals and surgeons
      are remunerated. In addition, the impact of the time taken to train a surgeon to
      carry out laparoscopic dismembered pyeloplasty competently may play a significant
      role. Until these issues are resolved, definitive recommendation for the
      treatment of ureteropelvic junction obstruction will continue to be made on an
      individual basis.

PMID- 16999622
TI  - Case report: relief of acute obstruction of the Detour subcutaneous pyelovesical
      bypass.
AB  - A 36-year-old patient was admitted to the emergency department with complaints of
      severe flank pain, nausea, vomiting, anuria, and general illness. Five months
      earlier, we had placed a subcutaneous pyelovesical prosthesis (Detour; Porges) of
      the ureter for treatment of a chronically dilated upper urinary tract in a
      solitary right kidney previously treated by double-J stenting. Ultrasonography of
      the right kidney revealed severe hydronephrosis. A percutaneous nephrostomy
      catheter was placed, and antegrade pyelography showed complete obstruction of the
      prosthesis. Urinalysis and culture demonstrated a Candida infection. A systemic
      antimycotic was administered, and fluid management was started. On the third day,
      diuresis appeared, and antegrade nephrostomography confirmed patency of the
      bypass.

PMID- 16999623
TI  - Use of Holmium:YAG laser to facilitate removal of intravesical foreign bodies.
AB  - BACKGROUND AND PURPOSE: Foreign bodies in the bladder present a challenge to the
      urologist. Previously, endoscopic extraction, with or without perineal
      urethrotomy, or open cystotomy were the only treatment choices. We describe a
      novel use of the Ho:YAG laser for the removal of intravesical foreign bodies. We
      further tested the laser on objects that have been reported in the literature to
      necessitate open cystotomy to determine their suitability for endoscopic removal.
      MATERIALS AND METHODS: The Ho:YAG laser is introduced through the cystoscope and
      used to cut large foreign bodies into a size that can be extracted through the
      urethra. We tested the Ho:YAG laser ex vivo on other objects that have been
      reported as intravesical foreign bodies. RESULTS: We removed a large complex
      foreign body with the laser that would otherwise have necessitated open
      cystotomy. No injury or sequela was observed. Many commonly reported intravesical
      foreign objects seem amenable to similar treatment. CONCLUSION: The Ho:YAG laser
      should be considered for use to facilitate removal of foreign bodies from the
      bladder.

PMID- 16999624
TI  - Percutaneous ultrasound-guided cryoablation of renal tumors using the CIVCO
      assist positioning system.
AB  - Cryoablation is emerging as an accepted treatment for small renal tumors.
      Percutaneous placement of cryoprobes using ultrasound guidance is an attractive
      option for patients with tumors easily seen with transabdominal ultrasonography;
      however, the placement of probes using hand-held devices is technically
      challenging. To improve the accuracy and ease of cryoprobe placement during
      percutaneous renal cryoablation, we describe the novel application of the CIVCO
      Assist positioning arm system during these complex procedures.

PMID- 16999625
TI  - Case report: Cowper's syringocele treated with Holmium:YAG laser.
AB  - A syringocele is a cystic dilation of Cowper's duct. We report on a 15-year-old
      boy with persistent dysuria attributable to a syringocele, which was treated by
      endoscopic unroofing with the holmium:YAG laser. The classification,
      pathophysiology, and management options of Cowper's syringocele are briefly
      reviewed.

PMID- 16999626
TI  - Laparoscopic urethrovesical anastomosis: a model to assess surgical competency.
AB  - PURPOSE: To create a model for the evaluation of resident competency and
      performance of laparoscopic skills in compliance with Accreditation Council for
      Graduate Medical Education (ACGME) outcome assessment guidelines for urology
      residency programs. MATERIALS AND METHODS: A model of laparoscopic interrupted
      urethrovesical anastomosis was developed using chicken skin from a local
      supermarket. Eight residents at various training levels utilized a simulator with
      a camera-operating assistant to practice placing interrupted stitches. The time
      necessary for completion of an anastomosis and the quality of the anastomosis
      were documented. RESULTS: The time required to recreate a simulated
      urethrovesical anastomosis by placing six interrupted stitches declined from an
      initial mean of 60.75 minutes to 20.5 minutes after each resident had performed
      20 anastomoses each. The mean improvement was 39.5 minutes, with one postgraduate
      year-3 resident demonstrating an improvement of 50 minutes. CONCLUSION: This
      model can be used by ACGME-certified urology residency programs to assess the
      laparoscopic skills of residents.

PMID- 16999627
TI  - Rapid communication: bipolar PlasmaKinetic transurethral resection of the
      prostate: reliable training vehicle for today's urology residents.
AB  - BACKGROUND AND PURPOSE: With the improvement of medical therapy and minimally
      invasive surgical treatments for benign prostatic hyperplasia, the number of
      transurethral resections of the prostate (TURPs) done in training is decreasing.
      With fewer TURPs being performed, proficiency in this basic urologic technique
      has decreased, causing longer resection times. This often leads to a higher risk
      of fluid absorption, water toxicity, and hyponatremia (TUR syndrome). We examined
      the safety of bipolar electrocautery TURP (saline TURP) with the Gyrus
      PlasmaKinetic system using normal saline as irrigant. PATIENTS AND METHODS:
      Twenty-one men aged 54 to 85 years (median 70.0 years) underwent saline Plasma-
      Kinetic TURP from June 2002 to August 2003. Serum sodium, chloride, hemoglobin,
      and hematocrit were measured 1 hour prior to and 1 hour after TURP. Resection
      time, tissue weights, hospital stay, and catheter time were recorded and
      analyzed. RESULTS: The median preresection and postresection sodium
      concentrations were 139.0 mEq/mL and 140.0 mEq/L, respectively (ranges 130-142
      mEq/L and 134-143 mEq/L). The corresponding chloride values were 106.5 mEq/L and
      109.0 mEq/L (ranges 102-114 mEq/L and 106-116 mEq/L), and the hemoglobin and
      hematocrit values were 13.4 g/dL and 40.1 g/dL (8.7-15.2 g/dL and 33.7-46.7 g/dL)
      and 12.0 g/dL and 36.6 g/dL (8.2-14.4 g/dL and 27.5-43.7 g/dL), respectively. The
      median resection time was 65 minutes (range 45-140 minutes), and the median
      resected tissue weight was 20 g (range 5-61 g). There was no statistically
      significant difference between the preresection and postresection sodium
      concentrations, and no patient exhibited any clinical sign of TUR syndrome.
      CONCLUSION: Gyrus PlasmaKinetic TURP using normal saline as the irrigant is a
      safe alternative to and is technically no different from traditional monopolar
      TURP. The system also provides the longer time needed to train urology residents
      without compromising patient safety.

PMID- 16999628
TI  - Focal prostate cryoablation: initial results show cancer control and potency
      preservation.
AB  - BACKGROUND: Focal prostate cryoablation is the less-than-complete ablation of the
      gland with ice. Known tumor is ablated aggressively, whereas contralateral
      prostate tissue and surrounding structures are spared. This method offers
      targeted local cancer control aiming at sexual potency and urinary continence
      preservation in patients whose prostate cancer is believed to be unilateral.
      PATIENTS AND METHODS: Patients who had a strong desire for preservation of sexual
      function and continence were informed of focal prostate cryoablation as an
      investigational treatment option for clinically organ-confined, unilateral tumor
      identified by color Doppler ultrasonography and confirmed by targeted and
      systematic biopsy. Only stage, not preoperative serum prostate specific antigen
      concentration (PSA) or tumor differentiation, was considered a potential
      contraindication. Thirty-one men with a mean age of 63 years underwent the
      procedure. Follow-up consisted of PSA measurement every 3 months for 1 year and
      every 6 months thereafter, with biopsies at 6 months and 1, 2, and 5 years and
      following any three consecutive PSA rises. Potency was determined with a patient
      questionnaire filled in without the physician present. RESULTS: At a mean follow
      up of 70 months, biochemical disease-free status, according to the ASTRO
      definition, was maintained by 92.8% of patients (26/28) and a 96.0% negative
      biopsy rate (24/25) was observed. The one biopsy-positive patient was
      subsequently treated with full-gland cryoablation and remains disease free.
      Potency was maintained by 48.1% of patients (13/27) and another 40.7% (11/27)
      were potent with oral pharmaceutical assistance, yielding a total potency
      preservation rate of 88.9%. No complications were observed. CONCLUSION: Focal
      cryoablation can provide biochemical and local control of prostate cancer while
      preserving potency and continence. Further investigation is needed.

PMID- 16999629
TI  - Erectile dysfunction after PlasmaKinetic vaporization of the prostate: incidence
      and risk factors.
AB  - PURPOSE: To determine the incidence of erectile dysfunction (ED) after
      PlasmaKinetic vaporization of the prostate (PKVP) using objective and subjective
      parameters and risk factors. PATIENTS AND METHODS: A total of 153 men completed a
      questionnaire detailing perceived sexual dysfunction and underwent nocturnal
      penile-tumescence testing using the RigiScan for three consecutive nights 3 or 4
      days preoperatively and 3 months postoperatively. The International Index of
      Erectile Function (IIEF)-5 scores were obtained preoperatively and
      postoperatively. Full details of each operation were recorded, including grams of
      tissue resected, operative time, any short-term complications, especially
      emphasizing capsular perforation, and concomitant diseases such as diabetes and
      hypertension. The association of risk factors with the development of ED after
      PKVP was assessed. Complete data were available for 103 men (67.3%). Their mean
      age was 62.1 years (range 48-83 years). RESULTS: Postoperatively, 11 patients
      (10.6%) were found to have ED. Patients who developed ED postoperatively had a
      lower IIEF-5 score and penile-tumescence parameters preoperatively (for all
      parameters, P < 0.0001). As risk factors, diabetes, capsular perforation, and an
      IIEF-5 score <21 were found to be significant. CONCLUSIONS: The incidence of ED
      after PKVP measured objectively was 10.6%. In the absence of the risk factors,
      PKVP is a safe therapeutic strategy with regard to sexual function.

PMID- 16999630
TI  - Endocytoscopy: novel endoscopic imaging technology for in-situ observation of
      bladder cancer cells.
AB  - BACKGROUND AND PURPOSE: Recent advances in endoscopy have enabled microscopic
      imaging of live bladdercancer cells in situ. The newly developed Endocystoscopy
      system (Olympus Medical Systems Co., Tokyo, Japan) is a flexible digital
      endoscope that has more than a 450-fold magnifying power on a video monitor.
      PATIENTS AND METHODS: This supermagnifying endoscope was used to evaluate bladder
      carcinoma in five patients through the working channel of a rigid cystoscope.
      RESULTS: The cell structure and nuclear morphology were imaged adequately
      compared with conventional hematoxylin and eosin staining of a biopsy specimen.
      The tumors were graded correctly in four of five cases. CONCLUSION: This novel
      technology appears to be useful for histologic diagnosis during endoscopic
      examinations, potentially allowing us to avoid a conventional biopsy.

PMID- 16999634
TI  - A content analysis of news coverage of the HPV vaccine by U.S. newspapers,
      January 2002-June 2005.
AB  - Genital Human Papillomavirus (HPV) is the most common sexually transmitted
      infection in the United States. Of the 100 HPV types, HPV type 16 and HPV type 18
      have been demonstrated to cause cervical cancer. Two pharmaceutical manufacturers
      have developed and tested HPV vaccines and are applying to the FDA for licensure.
      This research describes the content of HPV vaccine information contained in news
      articles. The Lexis-Nexis database was used to identify 25 articles on HPV that
      were published in 285 U.S. newspapers from January 1, 2003 to June 17, 2005. The
      coding schema captured information about the news event and source, as well as
      HPV and cervical cancer, transmission, vaccine, potential impact of the vaccine,
      and its relationship to PAP tests. The content analysis revealed that the news
      coverage of HPV vaccine provides information on the experimental status and
      efficacy of the vaccine, explains link between HPV and cervical cancer, and
      reports the manufacturers by name, as well as relies on them for a news source.
      Detailed information about HPV, however, was frequently missing which could lead
      to an incomplete picture or lack of understanding of the complexity of HPV and
      cervical cancer. As a major source of medical information, the media can be
      particularly important in educating policy makers and the general public about
      new scientific advances. Public health officials may wish to collaborate with
      journalists, health educators, healthcare providers, and women's health advocates
      to ensure that future educational initiatives explain the complexity of the
      association of HPV and cervical cancer and to stress the importance of continued
      cervical cancer screening.

PMID- 16999635
TI  - Studies of multiple sclerosis in communities concerned about environmental
      exposures.
AB  - Multiple sclerosis (MS) is an autoimmune disease that differentially affects
      women, people 30-60 years old, and Caucasians. Evidence indicates that it is a
      complex disease determined by both environmental factors and genetic
      susceptibility. People across the United States have expressed concern about
      perceived clusters of MS in their communities and the role of environmental
      exposures in the development of the disease. The Agency for Toxic Substances and
      Disease Registry (ATSDR) has funded several studies to address this issue,
      including a cluster investigation, several prevalence studies, and a case-control
      study. The cluster investigation illustrated that there are few data regarding
      the number of individuals with MS in the United States. Prevalence studies were
      conducted in Ohio, Missouri, and Texas to address this deficiency. The results
      support a regional difference in MS prevalence, although the reason for this
      difference is unclear. The results also underscore the need for additional
      epidemiological information about the distribution of MS in other areas of the
      United States and information on the underlying etiology of the disease. A case
      control study is currently being conducted to examine potential risk factors for
      MS, including the role of environmental exposures and genetic susceptibility.
      Future research on MS should focus on large-scale studies and include
      collaboration among researchers with varied fields of expertise, such as
      epidemiology, neurology, and genetics.

PMID- 16999636
TI  - Toward optimal health: Sandra R. Leiblum, PH.D. discusses sexual dysfunction in
      women. [Interview by Jodi R. Godfrey].

PMID- 16999637
TI  - Uterine fibroids: a review of health-related quality of life assessment.
AB  - OBJECTIVE: To summarize the literature describing the impact of uterine fibroids
      on health-related quality of life (HRQOL), the measures used to assess HRQOL, and
      related areas for future research. METHODS: A search of three electronic
      databases (MEDLINE, Embase, and Current Contents) was performed, and 40 papers
      were identified referencing leiomyoma or uterine fibroids and (health-related)
      quality of life (HRQOL). Studies including women with benign gynecological
      conditions other than uterine fibroids were also reviewed. RESULTS: The EQ-5D, SF
      36, and related generic measures are used to assess HRQOL in women with diverse
      gynecological conditions, including uterine fibroids. The UFS-QOL, a condition-
      specific measure, provides scores on symptom severity and six HRQOL dimensions.
      All instruments consistently demonstrate that HRQOL is considerably impaired in
      women with symptomatic uterine fibroids and that appropriate treatment can lead
      to improved QOL. CONCLUSIONS: The published data on HRQOL associated with uterine
      fibroids report significantly lower HRQOL scores for women with fibroids than for
      women without this disorder. Additional research is needed to confirm these
      findings and provide greater detail describing the specific domains most affected
      by uterine fibroids. These advances are necessary to effectively compare new
      treatment modalities vs. standard invasive therapies, such as hysterectomy.

PMID- 16999638
TI  - Device implant technique and consideration of body image: specific procedures for
      implantable cardioverter defibrillators in female patients.
AB  - OBJECTIVES: The purpose of this paper is to describe the psychological effects of
      implantable cardioverter defibrillator (ICD) implantation in female patients and
      to make clinical recommendations for providers to optimize health outcomes for
      women. BACKGROUND: Traditional ICD implantation produces visible scarring.
      Changes in physical appearance affect body image in all ICD recipients but may be
      more onerous in female ICD recipients. Electrophysiologists have described
      cosmetic approaches to device placement that appear promising and may warrant
      consideration in female patients. CONCLUSIONS: Active discussion and
      consideration of alternative device implant techniques are indicated in female
      patients. Female patients should also be given time to make preoperative
      decisions, and family members should be engaged in decision making. The
      investigation of cosmetic implants is noteworthy and could improve quality of
      life, adjustment, and psychological fitness of female ICD recipients.

PMID- 16999639
TI  - Obesity distribution and reproductive hormone levels in women: a report from the
      NHLBI-sponsored WISE Study.
AB  - PURPOSE: Relationships between body weight and disease are not straightforward.
      Central obesity appears to be a relatively greater cardiovascular risk factor
      than generalized obesity. The purpose of this study was to evaluate body mass
      index (BMI) and waist circumference and the association of obesity distribution
      with blood estrogen levels (estradiol, bioavailable estradiol, and estrone).
      METHODS: The study cohort consisted of 207 postmenopausal women enrolled in the
      Women's Ischemia Syndrome Evaluation (WISE) undergoing angiography for evaluation
      of suspected ischemia. RESULTS: Both BMI and waist circumference were positively
      associated with all three blood estrogen levels (p < 0.01), with the highest
      estrogen levels found in the obese women with large waists (p < 0.01). Results
      from regression analyses confirmed significant associations of BMI and waist
      circumference with the estrogen levels. CONCLUSIONS: These results demonstrate
      differing relationships between blood estrogen levels and obesity distribution in
      a cohort of postmenopausal women with chest pain undergoing coronary angiography.
      The differing levels by general and central obesity may help explain in part
      observed epidemiological relationships between obesity and disease.

PMID- 16999640
TI  - Healthy women with a family history of breast cancer: impact of a tailored
      genetic counseling intervention on risk perception, knowledge, and menopausal
      therapy decision making.
AB  - BACKGROUND: Women with a family history of breast cancer have several menopausal
      therapy options, including tamoxifen, hormone therapy (HT), alternative
      medications, or no treatment. This complex decision should be based on each
      woman's risk to develop breast cancer, menopausal symptoms, preferences, and
      risks for other conditions. The authors determined the effects of a personalized
      risk assessment and genetic counseling intervention on knowledge, risk
      perception, and decision making in a group of healthy women who had a first
      degree relative with breast cancer. METHODS: Forty-eight cancer-free menopausal
      women age > or =40 years who had at least one first-degree relative with breast
      cancer were randomized to a genetic counseling intervention or control.
      Intervention participants were given a personalized risk assessment for breast
      cancer, heart disease, osteoporosis, and uterine cancer based on family history
      and personal health data. Knowledge, risk perception, and medication usage were
      measured at baseline, 1 month, and 6 months. RESULTS: Knowledge was higher in the
      intervention group at both follow-up time points postintervention. Perceived risk
      for developing breast cancer was significantly lower and more accurate in the
      intervention group at 1 and 6 months postintervention than at baseline, as was
      perceived risk of developing heart disease. Although the counseling intervention
      did affect both knowledge and risk perception, overall, both groups were
      reluctant to take any form of menopausal therapy. CONCLUSIONS: A personalized
      risk assessment and genetic counseling intervention improves patient knowledge
      and risk perception; however, it is unclear that the intervention influenced
      menopausal treatment decisions.

PMID- 16999641
TI  - Escitalopram for perimenopausal depression: an open-label pilot study.
AB  - BACKGROUND: Women have a relatively high risk of experiencing depressive episodes
      during the perimenopause. Indications for and acceptance of hormone replacement
      therapy (HRT) are increasingly controversial, and serotonin reuptake inhibitor
      antidepressants are an attractive potential treatment option for both the mood
      and somatic symptoms of perimenopause. METHODS: This study is an open-label, 8
      week trial of escitalopram for perimenopausal depression and somatic symptoms
      associated with perimenopause. Twenty women received escitalopram and were
      serially assessed with the Hamilton Rating Scale for Depression (HAMD, 30-item),
      the Greene Climacteric Scale (GCS), and the Clinical Global Impression (CGI).
      RESULTS: There were significant differences between pretest and posttest scores
      for each measure, as demonstrated in an intent-to-treat analysis: GCS (p <
      0.0001), HAM-D30 (p < 0.0001), and CGI (p < 0.0001). Two subjects dropped out
      prior to the second visit because of drug side effects. In this study, benefits
      of treatment were observed in several domains of perimenopausal symptoms,
      including those representative of psychological, vasomotor, and somatic symptoms.
      The limitations of this study are small sample size and lack of placebo control.
      CONCLUSIONS: Larger, long-term, controlled trials of antidepressants are
      warranted for the treatment of perimenopausal depression and associated somatic
      symptoms.

PMID- 16999642
TI  - The prevalence and age-related characteristics of pain in a sample of women
      veterans receiving primary care.
AB  - BACKGROUND: Women veterans are a growing but understudied population believed to
      be at increased risk for pain problems. Because of risk factors and clinical
      observations, we hypothesized that women veterans might have a high prevalence of
      pain and, thus, sought to determine the prevalence of (and age-related variations
      in) pain and to characterize several key pain dimensions in a sample of women
      veterans. METHODS: Women with routine appointments at the VA Connecticut Women's
      Health Center were recruited for study. Participants completed a 59-item
      questionnaire that provided information about their demographic, clinical, and
      pain status, as well as use of health services. RESULTS: Of 236 women approached,
      213 (89%) completed the questionnaire. The mean age was 52 years, and most (78%)
      reported an ongoing pain problem. For those reporting pain, the mean duration of
      pain was 6 years, average pain intensity was 6.3 (range 1-10), and commonly
      endorsed pain sites included lower extremity (68%), low back (63%), and shoulder
      (48%). The most frequently endorsed treatment (by 80%) was analgesic medication
      use. Across the four age categories (20-35, 36-50, 51-65, and > or =66 years),
      pain prevalences were 64%, 89%, 83%, and 69%, respectively. Although pain
      intensity levels did not vary across age groups, older women (> or =66) reported
      using fewer pain treatments, including analgesic medications. Finally, those with
      (vs. those without) pain reported a greater number of medical and mental health
      visits in the preceding year. CONCLUSIONS: This study documented a significantly
      high prevalence of pain among a sample of women veterans receiving primary care
      in a VA women's health clinic.

PMID- 16999643
TI  - Reducing urinary tract infections among female clean room workers.
AB  - OBJECTIVES: A higher prevalence of urinary tract infection (UTI) was observed
      among clean room workers than among others in our previous study in 2001. We
      implemented intervention programs for reducing UTI and evaluated their effects 2
      years later. METHODS: We conducted an intervention study in four factories in the
      industrial park where the previous study was conducted and recruited participants
      from women workers who received annual health examinations at the clinic of the
      park. The intervention included health education programs during the new employee
      orientation and seasonal on-the-job training. We also implemented other measures,
      including placing posters in the workplace and disseminating knowledge of UTI
      prevention through e-mail and oral communications. One-on-one education was
      provided to workers who were found to have UTI in the previous study. RESULTS:
      All the 1666 qualified workers, including 1414 clean room workers and 252
      nonclean room workers, agreed to participate. We found a similar prevalence (both
      0.8%) of symptomatic UTIs (patients with clinical symptoms, such as voiding
      frequency, urgency, and burning sensation during voiding) in clean room and
      nonclean room workers. In the 366 participants who also participated in the
      previous study, we found a significant decrease in the prevalence of UTI (from
      9.8% to 1.6%) and significant increases in the prevalence of water intake and
      urine voiding, three times or more during a shift (p < 0.001 for all McNemar
      tests). CONCLUSIONS: The interventions had achieved behavior modification and
      decreases in the prevalence of UTI.

PMID- 16999644
TI  - The influence of gender on colorectal cancer stage: the state of Ohio, 1996-2001.
AB  - PURPOSE: The authors sought to determine if colorectal cancer stage at diagnosis
      varies by gender in the state of Ohio. METHODS: We conducted a retrospective
      cohort study. Included in the cohort were patients diagnosed with colorectal
      cancer from 1996 to 2001 who had their data reported to the State of Ohio Tumor
      Registry. We collected data on gender, stage of cancer, and three potential
      confounding variables: age, location of colon cancer, and race. The colorectal
      cancer was determined to be at one of four stages: (1) carcinoma in situ, (2)
      local disease, (3) regional disease, and (4) distant disease. In addition, we
      combined stages 1 and 2 to create a good prognosis category, and we combined
      stages 3 and 4 to create a bad prognosis category. RESULTS: Our cohort consisted
      of 27,041 patients [13,807 women (51%) and 13,234 men]. The women with colon
      cancer were significantly older and had more right-sided colon cancer, (p <
      0.05). With the use of logistic regression, the women were significantly less
      likely to have carcinoma in situ compared with the men (OR = 0.82, 95% CI 0.75
      0.89). The women also had a significant decrease in local disease (OR = 0.94, 95%
      CI 0.89-0.99). In contrast, the women showed significantly more regional disease
      than men (OR = 1.11, 95% CI 1.05-1.16). The women were less likely to have a good
      prognostic stage (OR = 0.89, 95% CI 0.85-0.94) and more likely to have a bad
      prognostic stage (OR = 1.12, 95% CI 1.07-1.18). CONCLUSIONS: In the State of Ohio
      from 1996 to 2001, women had more advanced colon cancer at diagnosis than men.

PMID- 16999646
TI  - Clinical and economic outcomes of pharmacist-managed antiepileptic drug therapy.
AB  - This study explores the associations between pharmacist-managed antiepileptic
      drug therapy in hospitalized Medicare patients and diagnoses indicating the need
      for these drugs. It also explores the following major heath care outcomes: death
      rate, hospital length of stay (LOS), Medicare charges, drug charges, laboratory
      charges, complications, and adverse drug reactions. Data were drawn from the 1998
      MedPAR and 1998 National Clinical Pharmacy Services databases. Pharmacist-managed
      antiepileptic drug therapy was evaluated in a study population of 9380 Medicare
      patients with diagnosed epilepsy or seizure disorders treated in 794 United
      States hospitals. This population was derived from the 38,311 hospitalized
      Medicare patients with epilepsy or seizure disorders (MedPAR). In hospitals
      without pharmacist-managed antiepileptic drug therapy, death rates were 120.61%
      higher, with 374 excess deaths (chi(2)=5.983, df=1, p=0.014, odds ratio
      [OR]=1.553, 95% confidence interval [CI] 1.102-2.189). Hospital LOS was 14.68%
      higher, with 8069 patient-days (Mann-Whitney U test [U]=3833132, p=0.0009); total
      Medicare charges were 11.19% higher, with 14,372,550 dollars in excess total
      charges (U=3644199, p=0.0003); per-patient drug charges were $115 +/- $92 higher
      (p=NS); laboratory charges were 32.24% higher, with 5,664,970 dollars in excess
      charges; and aspiration pneumonia rate was 54.61% higher (chi(2)=5.848, df=1,
      p=0.015, OR=1.233, 95% CI 1.081-1.901). Although the frequencies of other
      complications and adverse effects were higher, these differences were not
      statistically significant compared with hospitals with pharmacist-managed
      antiepileptic drug therapy. Clinical and economic outcomes were improved among
      hospitalized Medicare patients whose antiepileptic drug therapy was managed by
      pharmacists.

PMID- 16999647
TI  - Nonsteroidal antiinflammatory drugs and acute myocardial infarction in patients
      with no major risk factors.
AB  - STUDY OBJECTIVE: To assess the risk of long-term use of five nonsteroidal
      antiinflammatory drugs (NSAIDs)--rofecoxib, celecoxib, ibuprofen, naproxen, and
      diclofenac--in relation to acute myocardial infarction. DESIGN: Five separate
      nested case-control studies, one for each NSAID, designed to minimize important
      biases present in other observational studies. Setting. University-affiliated
      research program. Data Source. The United Kingdom General Practice Research
      Database (GPRD). MEASUREMENTS AND MAIN RESULTS: We identified all people in the
      GPRD aged 30-79 years who had a first recorded prescription for rofecoxib,
      celecoxib, ibuprofen, naproxen, or diclofenac after January 1, 1999. Cases of
      newly diagnosed, first-time acute myocardial infarction were then identified from
      the study population, along with matched control subjects. Relative risk
      estimates for acute myocardial infarction in patients with no recorded major
      clinical risk factors for acute myocardial infarction were determined for each
      NSAID according to receipt of 2-4, 5-9, 10-19, or 20 or more prescriptions
      compared with receipt of only 1 prescription. Results were adjusted for relevant
      variables possibly related to the risk for acute myocardial infarction. No
      material elevation of risk according to the number of prescriptions received for
      ibuprofen or naproxen was noted. However, a substantial increased risk similar to
      that found in clinical trials was noted in patients who received 10 or more
      prescriptions for rofecoxib, celecoxib, or diclofenac. CONCLUSION: Extensive use
      of rofecoxib, celecoxib, and diclofenac increases the risk of acute myocardial
      infarction, but similar use of ibuprofen and naproxen does not.

PMID- 16999648
TI  - Long-term safety of pioglitazone versus glyburide in patients with recently
      diagnosed type 2 diabetes mellitus.
AB  - STUDY OBJECTIVE: To evaluate the long-term safety and efficacy of glyburide
      versus pioglitazone in patients with a recent diagnosis of type 2 diabetes
      mellitus. DESIGN: Prospective, randomized, multicenter, double-blind trial with a
      16-week titration period and a 40-week maintenance period. SETTING: Sixty-five
      investigative sites in the United States and Puerto Rico. PATIENTS: Five hundred
      two subjects with a recent diagnosis of type 2 diabetes that was unsuccessfully
      treated with diet and exercise were randomly assigned to study treatment. Of the
      251 patients in each treatment group, 128 (51.0%) glyburide-treated patients and
      134 (53.4%) pioglitazone-treated patients completed the study. INTERVENTIONS:
      Dosages of randomly assigned glyburide and pioglitazone were titrated every 4
      weeks for 16 weeks in 5-mg/day and 15-mg/day increments, respectively, until a
      fasting plasma glucose level between 69 and 141 mg/dl was achieved. The optimized
      regimen was maintained during the subsequent 40-week double-blind phase.
      MEASUREMENTS AND MAIN RESULTS: At week 56, glyburide and pioglitazone improved
      glucose control comparably (change in hemoglobin A(1c) -2.02% and -2.07%,
      respectively, p=0.669). Withdrawal due to lack of efficacy or adverse events
      occurred more frequently with glyburide (20.8%) than pioglitazone (12.8%,
      p<0.032). Significantly higher percentages of glyburide- than pioglitazone
      treated patients had a hypoglycemic (24.3% vs 4.4%, p=0.0001) or cardiac (8.8% vs
      4.4%, p=0.0478) event. Edema (4.8% vs 7.9%, p=0.1443) and weight gain (4.4% vs
      4.0%, p=0.8238) did not differ significantly between the glyburide and
      pioglitazone groups. Only a few patients discontinued study drug because of
      weight gain (one glyburide, one pioglitazone), edema (one pioglitazone), or a
      cardiac event (two glyburide). CONCLUSION: With long-term treatment, both
      glyburide and pioglitazone resulted in comparable glycemic control; however,
      pioglitazone was associated with less hypoglycemia and fewer withdrawals due to
      lack of efficacy or adverse events.

PMID- 16999649
TI  - Effect of heliox on albuterol delivery by metered-dose inhaler in pediatric in
      vitro models of mechanical ventilation.
AB  - STUDY OBJECTIVE: To determine the effect of varying concentrations of heliox, a
      mixture of helium and oxygen, on albuterol delivery administered by metered-dose
      inhaler (MDI) in pediatric mechanically ventilated models. DESIGN: Prospective in
      vitro laboratory study. SETTING: University-affiliated research laboratory.
      MODELS: The lungs of a 10-kg infant and 30-kg child receiving humidified pressure
      regulated volume-controlled ventilation were simulated. The infant settings were
      an endotracheal tube (ETT) of 4.0 mm, tidal volume of 150 ml, positive end
      expiratory pressure of 2 cm H(2)O, rate of 20 breaths/minute, inspiratory time of
      0.7 second; the child settings were an ETT of 6.0 mm, tidal volume of 450 ml,
      positive end-expiratory pressure of 2 cm H(2)O, rate of 16 breaths/minute, and
      inspiratory time of 0.8 second. MEASUREMENTS AND MAIN RESULTS: Ten albuterol MDI
      canisters with chlorofluorocarbon propellants were each actuated once
      sequentially (total dose 1000 mug) with a commercially available aerosol holding
      chamber. Albuterol was collected onto a filter proximal to a lung simulator. The
      filter was rinsed, and concentrations were determined by high-performance liquid
      chromatography. In the infant model, heliox mixtures of 70:30, 60:40, and 50:50
      were compared with nitrogen:oxygen (N(2):O(2)) mixtures in the same ratios. The
      effect of the 70:30 mixtures was also explored in a child model. Each gas mixture
      was tested 5 times. At all three ratios, albuterol delivery to the end of the ETT
      was improved with heliox compared with N(2):O(2) (approximately 7% vs 3-4%,
      p<0.0001, one-way analysis of variance [ANOVA] with a Bonferroni correction for
      multiple comparisons). No significant difference was noted in mean percentage
      albuterol delivery among the varying ratios of heliox studied. By two-way ANOVA,
      significantly greater albuterol delivery was noted with 70:30 heliox compared
      with 70:30 N(2):O(2) (7-8% vs 3%, p<0.0001), with no significant difference
      between the infant and child model (p=0.21). The gas mixture, model, and
      interaction of the two explained 88% of the variability in mean percentage
      albuterol delivery. CONCLUSION: Heliox increased albuterol delivery administered
      by MDI to the end of the ETT in these in vitro pediatric models of mechanical
      ventilation. Further studies are needed to determine if the improved albuterol
      delivery with heliox enhances clinical response in infants and children needing
      mechanical ventilation.

PMID- 16999650
TI  - Life after the women's health initiative: evaluation of postmenopausal symptoms
      and use of alternative therapies after discontinuation of hormone therapy.
AB  - STUDY OBJECTIVE: To determine the number of women who have menopausal symptoms
      after discontinuing hormone therapy, to determine how many of these women
      subsequently require nonhormonal alternatives to manage their symptoms, and to
      assess the effectiveness of those therapies. DESIGN: One-year retrospective
      study. SETTING: Department of Family Medicine outpatient clinic at a university
      medical center. PATIENTS: From 378 postmenopausal women who discontinued hormone
      therapy between August 1, 2002, and August 31, 2003, we randomly selected 78
      using electronic medical records to provide a sample with a 95% confidence
      interval and a 10% margin of error. MEASUREMENTS AND MAIN RESULTS: Reasons why
      the women discontinued therapy and any nonhormonal alternative therapies that
      they may have used to manage subsequent menopausal symptoms were recorded. The
      primary investigator contacted the 78 women to complete a telephone survey. In
      most women, at least one menopausal symptom recurred. Vasomotor symptoms (hot
      flashes) were most common and occurred in 41 (53%) women. In addition, 59 (76%)
      women reported using nonhormonal alternative therapies, and 40 (68%) of this
      group deemed the alternatives helpful. CONCLUSION: We strongly believe that
      health care providers, including pharmacists, must continue to communicate with
      and educate women regarding treatment options for menopausal symptoms. Clinical
      pharmacists are ideally suited to contribute to ongoing research in this area.

PMID- 16999651
TI  - A practical approach to hyperglycemia management in the intensive care unit:
      evaluation of an intensive insulin infusion protocol.
AB  - STUDY OBJECTIVES: To evaluate the effectiveness and safety of maintaining a
      target blood glucose concentration of 91-130 mg/dl with a standardized, nurse
      managed, intensive insulin infusion protocol outside a study setting, and to
      determine if a statistically significant favorable effect on morbidity and
      mortality was achieved. DESIGN: Retrospective, observational, chart review.
      SETTING: Medical and surgical intensive care units (ICUs) in a community teaching
      hospital. PATIENTS: One hundred forty-three adult patients who received insulin
      infusions managed at the discretion of the physician over a 1-year period before
      initiation of the protocol (control group), and 70 patients who received insulin
      infusions over a 6-month period with infusion dosages titrated by using the
      protocol (protocol group). MEASUREMENTS AND MAIN RESULTS: Episodes of
      hypoglycemia, time within target range, mean blood glucose concentration,
      frequency of measurement, length of ICU stay, duration of mechanical ventilation,
      and overall mortality were collected. Hypoglycemic episodes were not
      significantly different between the groups. Blood glucose concentrations were
      within target range in 34% of all measurements in the protocol group compared
      with 23% in the control group (p<0.001, relative risk [RR] 1.48, 95% confidence
      interval [CI] 1.38-1.58). Once target range was reached on one measurement, 43%
      of concentrations remained in target range in the protocol group compared with
      29% in the control group (p<0.001, RR 1.47, 95% CI 1.38-1.56). Frequency of
      measurements was higher in the protocol group versus control group (p=0.01);
      however, clinical difference was minimal. Protocol group had lower overall
      mortality rate (27% [19/70] vs 32% [46/143], p=0.45), reduced mean ICU length of
      stay (16.7 +/- 10.6 vs 18.4 +/- 16.0 days, p=0.37), and less mechanical
      ventilation time (16.5 +/- 9.7 vs 17.0 +/- 15.0 days, p=0.79). CONCLUSION: The
      nurse-managed insulin infusion protocol improved glycemic control with minimal
      hypoglycemic episodes compared with baseline practice. A trend toward decreased
      mortality, ICU length of stay, sand days of mechanical ventilation was observed.
      When compared with other published protocols, our insulin protocol displays
      comparable effectiveness with the use of less-frequent blood glucose
      measurements.

PMID- 16999652
TI  - Management of diabetes mellitus in hospitalized patients: efficiency and
      effectiveness of sliding-scale insulin therapy.
AB  - STUDY OBJECTIVE: To determine the efficiency and effectiveness of current
      prescribing practices relative to short- and intermediate-acting insulins in the
      prevention or treatment of acute hyperglycemic episodes in hospitalized patients
      with diabetes mellitus or hyperglycemia, and to identify clinical findings that
      influence the effectiveness of insulin therapy in these patients. DESIGN:
      Retrospective observational study. SETTING: University-affiliated hospital.
      PATIENTS: Ninety consecutive adult inpatients who had orders placed for as-needed
      subcutaneous regular or lispro sliding-scale insulin. MEASUREMENTS AND MAIN
      RESULTS: Medical records were reviewed for patients' clinical characteristics and
      responses to administered insulin that were recorded during each of the first 5
      days of hospitalization in which sliding-scale insulin therapy was used. Despite
      the immediate or bedside availability of both computerized and manual means to
      record finger-stick blood glucose levels and insulin injections, uncertainties or
      missing information related to execution, timing, blood glucose levels, or
      insulin dose were present in approximately 30% of all anticipated points of care
      involving insulin. Ten episodes of hypoglycemia in six patients were associated
      with sliding-scale insulin. Appropriately timed, successive glucose measurements
      documented a decrement in elevated blood glucose values to within the target
      range of 90-130 mg/dl after 76 (12%) of 621 sliding-scale insulin injections.
      Glucose levels remained elevated, and insulin effects were therefore
      subtherapeutic after 523 injections (84%). Despite blood glucose levels that
      remained persistently elevated, corresponding adjustments in either the timing or
      the dose of insulin were made infrequently. Sliding-scale insulin regimens were
      never adjusted in 73 patients (81%). Through 5 days of therapy, the proportion of
      patients who attained good glycemic control ranged from 2-10% (mean 6%). The mode
      of overall glycemic control was poor, with 51-68% of patients in this category on
      any given day. Overall, treated diabetic and hyperglycemic patients were more
      likely to be poorly controlled than relatively well controlled. CONCLUSION: Our
      findings reveal outcomes associated with sliding-scale insulin that are widely
      variable, often ineffectual, and prone to deficiencies in monitoring,
      documentation, and prescribing soundness. Efforts to improve glycemic control in
      hospitalized patients are clearly needed.

PMID- 16999653
TI  - Effect of long-term tacrolimus immunosuppression on renal function in liver
      transplant recipients.
AB  - STUDY OBJECTIVES: To describe changes in renal function occurring after long-term
      treatment with tacrolimus in clinically stable liver transplant recipients, and
      to identify risk factors for a clinically significant decline in renal function
      in these patients. DESIGN: Retrospective cohort study. Setting. University
      medical center. Patients. Four hundred thirty-two patients aged 18 years or older
      who underwent liver transplantation between January 1, 1996, and December 31,
      2000, and received tacrolimus as part of their immunosuppressive treatment
      regimen. MEASUREMENTS AND MAIN RESULTS: Six hundred patients were identified from
      an electronic records review. Those who received multiorgan transplants, were not
      receiving their first liver transplant, or died during the hospitalization were
      excluded from the study. Outcomes measured were change in mean glomerular
      filtration rate (GFR) up to 5 years after transplantation, and proportion of
      patients with a decline in GFR of 30% or greater from baseline to the last
      recorded serum creatinine level. Covariates that affected this decline were
      identified using a logistic regression model. Patients were followed for a mean
      +/- SD of 3.7 +/- 2.0 years. Mean GFR showed a statistically significant decline
      from baseline to end of follow-up (67.7 +/- 25.6 vs 58.4 +/- 26.5 ml/min/1.73
      m(2), p<0.001). The GFR declined by 30% or more in 154 (35.6%) patients.
      Increasing age (odds ratio [OR] = 1.03, p=0.020), female sex (OR = 1.92,
      p=0.006), higher baseline GFR (OR = 1.03, p<0.001), and diagnosis of diabetes
      mellitus (OR = 1.74, p=0.059) were identified as predictors of this outcome.
      CONCLUSION: After the acute posttransplantation period, liver transplant
      recipients given long-term treatment with tacrolimus experienced only small
      changes in GFR over time. Patients with diabetes and women had the highest risk
      of experiencing a clinically significant decline in renal function.

PMID- 16999654
TI  - Incidence and economic implications of heparin-induced thrombocytopenia in
      medical patients receiving prophylaxis for venous thromboembolism.
AB  - STUDY OBJECTIVES: To determine the incidence of heparin-induced thrombocytopenia
      (HIT) in patients admitted to a medical service who were given unfractionated
      heparin (UFH) or low-molecular-weight heparin (LMWH) to prevent venous
      thromboembolism, the incremental cost of developing HIT, and the cost
      consequences of using LMWH to prevent venous thromboembolism in medical patients.
      DESIGN: Retrospective analysis with a nested case-control. SETTING: University
      affiliated tertiary-care hospital. PATIENTS: A total of 10,121 adult medical
      patients admitted between August 1, 2000, and November 2, 2004, received UFH or
      LMWH to prevent venous thromboembolism during their admission. From these,
      patients with immune-mediated HIT were identified and served as case patients,
      and 3-5 matched control patients were identified for each case patient.
      MEASUREMENTS AND MAIN RESULTS: The development of HIT was determined for patients
      who received LMWH and for patients who received UFH. Costs were compared between
      the patients with HIT and the matched control patients. The cost of using LMWH to
      prevent venous thromboembolism was compared with the cost of using UFH. In
      patients receiving UFH and those receiving LMWH, the incidence of HIT was 0.51%
      (43/8420) and 0.084% (1/1189), respectively (p=0.037), with an overall incidence
      of 0.43% (44/10,121). Admissions that included development of HIT incurred an
      average cost of 56,364 dollars compared with 15,231 dollars (p<0.001) for
      admissions without HIT. Using LMWH to prevent venous thromboembolism in medical
      patients cost 13.88 dollars less per patient than using UFH. CONCLUSIONS: For the
      prophylaxis of venous thromboembolism, LMWH was associated with a lower incidence
      of HIT than UFH in medical patients. An admission during which the patient
      develops HIT costs significantly more than an admission during which the patient
      does not develop HIT. Low-molecular-weight heparin is cost-effective for
      prevention of venous thromboembolism in medical patients.

PMID- 16999655
TI  - Anticoagulation-related outcomes in patients receiving warfarin after starting
      levofloxacin or gatifloxacin.
AB  - STUDY OBJECTIVE: To compare anticoagulation-related outcomes in patients
      receiving stable dosages of warfarin who started levofloxacin or gatifloxacin
      therapy. DESIGN: Retrospective medical record review. SETTING: Veterans Affairs
      medical center. PATIENTS: Of 92 patients receiving the same dosages of warfarin
      for at least 4 weeks before starting antibiotic therapy, 54 received levofloxacin
      between January and September 2003, and 38 received gatifloxacin between January
      and September 2004. MEASUREMENTS AND MAIN RESULTS: Data were obtained through the
      hospital's pharmacy, laboratory, and general patient databases and through
      electronic medical records. The INRs evaluated were prefluoroquinolone use,
      defined as the last INR measured before the start of antibiotic therapy (up to 4
      wks earlier), and postfluoroquinolone use, defined as any INR measured during
      antibiotic therapy through 1 week after discontinuation of the antibiotic.
      Analyzed outcomes included the percentage of patients with postfluoroquinolone
      INRs that were above 4, that exceeded the therapeutic goal, or that exceeded the
      goal by more than 1 point; INR changes of more than 0.5, 1, or 1.5 points above
      the INR before fluoroquinolone use; major or minor bleeding events; requirement
      for vitamin K administration; warfarin dosage reduction or withholding doses; and
      warfarin-related hospital, emergency, or urgent care admissions or visits. No
      significant differences were noted in baseline characteristics with regard to
      age, sex, prefluoroquinolone INR, or anticoagulation indications between the two
      groups. The percentage of patients with a postfluoroquinolone INR above 4 was 2%
      (1 of 54 patients) in the levofloxacin group versus 21% (8 of 38 patients) in the
      gatifloxacin group (p=0.003). The percentage of patients receiving vitamin K in
      the levofloxacin and gatifloxacin groups was 0% (0 of 54 patients) and 11% (4 of
      38, p=0.026), respectively. For the other anticoagulation-related outcomes, no
      significant differences were noted between the groups. CONCLUSION: Patients
      receiving warfarin who take gatifloxacin may be at higher risk for an INR above 4
      compared with those taking levofloxacin. Close monitoring of warfarin therapy
      while concomitantly receiving gatifloxacin is warranted.

PMID- 16999656
TI  - Oxygen therapeutics: oxygen delivery without blood.
AB  - Nearly 14 million units of packed red blood cells are transfused in the United
      States each year. According to the U.S. Department of Health and Human Services,
      in 1999, 6% of hospitals reported a shortage of blood, resulting in the
      cancellation or postponement of surgical procedures. The many limitations and
      risks of transfusions of packed red blood cells in critically ill patients have
      facilitated interest in developing alternative agents for oxygen delivery. Over
      the past few decades, safe and effective substitutes have been in development.
      However, no currently approved agent provides both oxygen transport and volume in
      place of packed red blood cells. Oxygen therapeutic products have several
      advantages compared with packed red blood cells, including a prolonged shelf
      life, lack of a cross-matching requirement, and minimal infectious risks or
      concerns about immunogenicity. Hemoglobin-based oxygen carriers and
      perfluorocarbons are being developed. Two products are undergoing clinical
      trials. Polyheme is undergoing a phase III study in trauma patients, and Hemopure
      is being evaluated in a phase II study in patients undergoing cardiopulmonary
      bypass surgery. A third product (Hemolink) was being evaluated in a phase III
      study in patients undergoing coronary artery bypass grafting surgery; however,
      the trial was suspended. In addition, several other hemoglobin-based oxygen
      carriers are in the preclinical stages. Oxygen therapeutics have several
      potential clinical applications in the management of perioperative blood loss,
      trauma, acute normovolemic hemodilution, traumatic brain injury, and blood
      requirements in patients who refuse or have contraindications to transfusions of
      red blood cells.

PMID- 16999657
TI  - Nesiritide: harmful or harmless?
AB  - Nesiritide is the recombinant form of human B-type (brain) natriuretic peptide
      (BNP), and its amino acid sequence is identical to that of endogenous human BNP.
      Administration of nesiritide results in venous and arterial vasodilation, as well
      as enhanced diuresis. Given the many limitations of therapies previously
      available for the treatment of acute decompensated heart failure, the
      anticipation was that nesiritide would offer a safer and more effective
      therapeutic option. Recently, two meta-analyses raised the question of safety
      with nesiritide therapy, specifically an increased risk of renal dysfunction and
      mortality. Although several studies generated information regarding the potential
      role of nesiritide in various settings, the questions raised by the meta-analyses
      are concerning. Our hope is that future clinical trials will address the concerns
      raised and provide a better understanding of the role of nesiritide in the
      management of acute decompensated heart failure. Until these data are available,
      nesiritide use should be limited.

PMID- 16999658
TI  - Use of low-molecular-weight heparin to bridge therapy in obese patients and in
      patients with renal dysfunction.
AB  - OBJECTIVE: To recommend strategies to bridge therapy with low-molecular-weight
      heparin (LMWH) in obese patients and in patients with renal dysfunction. METHODS:
      A MEDLINE search was performed of the literature from January 1966-November 2005.
      Published material dealing with bridging of anticoagulation therapy or short-term
      use of LMWH therapy in patients with renal dysfunction or obesity was reviewed.
      The manufacturers of enoxaparin, dalteparin, and tinzaparin were contacted for
      the references used to determine dosing recommendations. RESULTS: Although LMWH
      has been commonly used to bridge therapy, our search revealed no trials that
      specifically examined LMWH bridge therapy in obese patients or in patients with
      renal dysfunction. However, nine trials using LMWH in obese patients and 14
      trials using LMWH in patients with renal dysfunction were identified. When
      compared with normal-weight individuals, obese patients receiving enoxaparin and
      dalteparin based on total body weight did not demonstrate higher hemorrhage rates
      or antifactor Xa levels. Subtherapeutic antifactor Xa levels were more common
      with once-daily dosing of enoxaparin than with dosing every 12 hours. Enoxaparin
      accumulates in patients with a creatinine clearance of 30 ml/minute or less; in
      this population, enoxaparin dosage adjustments have been attempted. Tinzaparin
      does not accumulate in patients with a creatinine clearance of 20 ml/minute or
      greater after at least 10 days of dosing. CONCLUSION: Obese patients, weighing 90
      150 kg, receiving LMWH for bridge therapy should receive dosages based on total
      body weight. Unfractionated heparin is recommended in patients weighing more than
      150 kg; however, if LMWH is used, antifactor Xa levels should be monitored.
      Bridging with enoxaparin should be limited to patients with a creatinine
      clearance greater than 30 ml/minute. The use of enoxaparin 1 mg/kg once/day for
      patients with a creatinine clearance of 30 ml/minute or less is not recommended
      for anticoagulation bridge therapy. Tinzaparin may be considered for cross
      coverage of high-risk patients with recent or recurrent venous thromboembolism
      who have a creatinine clearance of at least 20 ml/minute.

PMID- 16999659
TI  - Carvedilol versus cardioselective beta-blockers for the treatment of hypertension
      in patients with type 2 diabetes mellitus.
AB  - Treatment with beta-blockers is recommended to achieve and maintain adequate
      blood pressure control in patients with hypertension, and these agents have been
      shown to decrease cardiovascular risk factors in patients with both hypertension
      and type 2 diabetes mellitus. However, beta-blocker therapy also may worsen
      glycemic and lipidemic control and may lead to microalbuminuria. A recent study
      showed a better metabolic profile with carvedilol than with metoprolol in
      patients with both type 2 diabetes and hypertension in the presence of renin
      angiotensin system blockade. This beneficial effect on metabolic components has
      been proposed as attributable to carvedilol's alpha-blocking effects or
      antioxidant properties. In this article, the pathophysiology of hypertension and
      type 2 diabetes and the association between them are reviewed, the pharmacologic
      properties of carvedilol are discussed, and clinical studies in the literature
      comparing carvedilol with selective beta-blockers in patients with both type 2
      diabetes and hypertension are identified and evaluated. This information should
      be useful to practitioners when selecting the optimum beta-blocker for treating
      hypertension in patients with type 2 diabetes.

PMID- 16999660
TI  - Illicit use of specific prescription stimulants among college students:
      prevalence, motives, and routes of administration.
AB  - OBJECTIVES: To explore the illicit use of specific prescription stimulants among
      college students and add to our understanding of reasons (motives) and routes of
      administration associated with illicit use of these drugs. METHODS: A random
      sample of 4580 college students self-administered a Web-based survey. The survey
      contained a variety of items pertaining to the illicit use of prescription
      stimulants. An extensive list of prescription stimulants was provided, and
      students were asked to select all the specific prescription stimulants that they
      had used illicitly. Items were also included to assess the motives and routes of
      administration associated with illicit use of prescription stimulants. RESULTS:
      Lifetime and past-year prevalence rates for illicit use of prescription
      stimulants were 8.3% (382 students) and 5.9% (269 students), respectively.
      Approximately three fourths (75.8%) of the 269 past-year illicit users of
      prescription stimulants reported using an amphetamine-dextroamphetamine
      combination agent (e.g., Adderall) in the past year, and approximately one fourth
      (24.5%) reported using methylphenidate (e.g., Ritalin, Concerta, Metadate,
      Methylin). Past-year illicit use of prescription stimulants was more than 3 times
      more likely among Caucasians (odds ratio [OR] 3.1, 95% confidence interval [CI]
      1.5-6.6) and Hispanics (OR 3.8, 95% CI 1.6-9.3) compared with African-Americans,
      and more than twice as likely among Caucasians (OR 2.1, 95% CI 1.3-3.4) and
      Hispanics (OR 2.6, 95% CI 1.4-5.1) compared with Asians. The most commonly
      reported motives for illicit use were to help with concentration (65.2%), help
      study (59.8%), and increase alertness (47.5%). Other motives included getting
      high (31.0%) and experimentation (29.9%). Nearly every illicit user (95.3%)
      reported oral administration, and 38.1% reported snorting prescription
      stimulants. CONCLUSION: Illicit use of amphetamine-dextroamphetamine is more
      prevalent than illicit use of methylphenidate formulations among college
      students.

PMID- 16999661
TI  - Workplace-based cardiovascular risk management by community pharmacists: impact
      on blood pressure, lipid levels, and weight.
AB  - STUDY OBJECTIVE: To assess the effectiveness of a community pharmacist-delivered
      cardiovascular case-management program by comparing body mass index (weight),
      systolic and diastolic blood pressure, and full lipid profile at the beginning of
      the program with these outcome measures at the end of the program. DESIGN:
      Retrospective data analysis using billing data submitted between July 1, 2001,
      and October 31, 2004, with a pre-post design in which subjects served as their
      own controls. SETTING: Manufacturing workplace in rural Iowa. PARTICIPANTS: Fifty
      six workers with risk factors for cardiovascular disease (mean age 40.67 yrs), 37
      had diabetes mellitus and 19 did not. INTERVENTION: During visits to the workers,
      pharmacists provided education about cardiovascular disease, identification of
      drug therapy problems, and importance of routine blood pressure, pulse, and
      weight measurements; they communicated with participants' physicians as needed.
      MEASUREMENTS AND MAIN RESULTS: The number of pharmacist visits/participant ranged
      from 1-13 (mean +/- SD 6.97 +/- 3.05). Outcome measures were weight, systolic and
      diastolic blood pressures, full lipid profiles (in patients with diabetes), and
      percentage of patients achieving treatment goal by the end of the 3 years.
      Statistically significant differences between the first and last visits were
      achieved for both systolic (124.12 +/- 11.07 and 120.36 +/- 14.39 mm Hg,
      respectively, p=0.016) and diastolic (80.4 +/- 9.01 and 77.43 +/- 9.14 mm Hg,
      respectively, p=0.019) blood pressure. The 19 patients without diabetes showed a
      statistically significant improvement in diastolic blood pressure (p=0.039), but
      the 37 patients with diabetes did not show a significant difference. A
      nonsignificant increase was seen in the percentage of patients with diabetes
      achieving low-density lipoprotein cholesterol (LDL) level goal between the first
      and last visits (p=0.06). CONCLUSION: A cardiovascular case-management program
      delivered in the workplace to middle-aged working adults by community pharmacists
      improved blood pressure and reduced LDL levels. The program was not effective,
      however, in weight reduction.

PMID- 16999662
TI  - Anticoagulation strategies for treatment of ischemic stroke and antiphospholipid
      syndrome: case report and review of the literature.
AB  - A 49-year-old Caucasian man with antiphospholipid syndrome who experienced an
      ischemic stroke required multidisciplinary decisions regarding acute and long
      term care. The patient first received warfarin and unfractionated heparin,
      followed by low-molecular-weight heparin. However, he developed complications
      from these drugs (warfarin-induced necrosis and heparin-induced
      thrombocytopenia), resulting in thigh necrosis and multiple additional cerebral
      and peripheral infarcts. His condition improved after warfarin and the heparins
      were discontinued, and a direct thrombin inhibitor, argatroban, was given
      intravenously for acute treatment. Argatroban is the only anticoagulant known to
      be safe in patients who experience an acute ischemic stroke in the setting of
      heparin-induced thrombocytopenia. For long-term anticoagulation, fondaparinux, an
      indirect, selective factor Xa inhibitor, was given subcutaneously. The patient
      received intravenous dexamethasone, later changed to azathioprine, for
      immunomodulatory treatment. He had significant improvement in his neurologic
      deficits without recurrent events over the next 18 months. Management of
      anticoagulation therapy in patients with antiphospholipid syndrome is complex and
      challenging, and therapeutic strategies need to be evaluated further.

PMID- 16999663
TI  - Plasmodium falciparum malaria associated with mefloquine failure in Gambia.
AB  - A 25-year-old Caucasian man developed Plasmodium falciparum malaria after
      traveling to Gambia, despite having received chemoprophylaxis with mefloquine.
      The patient was hospitalized after returning to the United States. He received a
      3-day course of atovaquone-proguanil and made a complete recovery. This case
      illustrates the potential role of pharmacists in the pharmaceutical care of
      travelers and underscores the importance of using current recommendations for
      preventing and treating malaria.

PMID- 16999664
TI  - Acute isoniazid toxicity and the need for adequate pyridoxine supplies.
AB  - A 25-year-old, 54-kg Hispanic man who had recently started multidrug therapy for
      pulmonary tuberculosis presented in status epilepticus after ingesting 9 g of
      isoniazid in a suicide attempt. Successful management of this patient required
      collaboration between several institutions to provide the large amount of
      necessary intravenous pyridoxine. Ultimately, this single overdose depleted the
      supply of intravenous pyridoxine for a significant region of the state of
      Nebraska. Isoniazid is commonly used to treat tuberculosis, but it is encountered
      relatively infrequently as the cause of an acute overdose. Severe isoniazid
      overdoses may present as seizure activity that is refractory to conventional
      antiepileptic therapy. Although intravenous pyridoxine is an effective antidote
      for isoniazid overdoses in patients presenting with status epilepticus, this
      agent has few indications and is typically stocked in limited quantities. In
      regions with large populations of patients who receive antituberculosis therapy,
      collaborative networks must be created to ensure that adequate supplies of
      intravenous pyridoxine (> or = 20 g) are available for effective treatment of
      isoniazid poisonings.

PMID- 16999665
TI  - Chemoprevention in prostate cancer.

PMID- 16999666
TI  - Doctors behaving badly?

PMID- 16999667
TI  - Clinical guidelines: what can we do to increase their use?

PMID- 16999668
TI  - Prisons: mental health institutions of the 21st century?

PMID- 16999669
TI  - Suicide in Australia: some good news.

PMID- 16999670
TI  - Diabetes guidelines: easier to preach than to practise?
AB  - OBJECTIVE: To review the management of glycaemia, blood pressure and serum lipids
      in a hospital outpatient diabetes clinic, the director of which co-authored the
      current national diabetes management guidelines. DESIGN: Retrospective audit.
      SETTING: Outpatient diabetes clinic in a tertiary referral teaching hospital,
      Sydney, NSW. STUDY POPULATION: 96 patients with type 1 diabetes (mean age, 44.4
      [SD, 12.8] years) and 509 patients with type 2 diabetes (mean age, 64.4 [SD,
      12.0] years) attending the clinic in 2003, who had undergone formal review of
      complications. MAIN OUTCOME MEASURES: Weight, height, control and treatment of
      glycaemia, blood pressure and serum lipids, and prevalence of diabetic
      microvascular complications. RESULTS: Glycated haemoglobin (HbA(1c)) was < 7% in
      13% of type 1 and 30% of type 2 diabetes patients, and > 8% in 47% and 34%,
      respectively. 35% of patients with type 1 diabetes and 71% of patients with type
      2 diabetes were treated with antihypertensive agents. Of these patients, 29% and
      24%, respectively, had blood pressure readings </= 130/80 mmHg. Among patients
      not treated with hypertensive agents, blood pressure readings were </= 130/80
      mmHg in 60% of type 1 and 38% of type 2 diabetes patients. About 30% of patients
      with type 1 diabetes and 50% of those with type 2 diabetes were being treated
      with lipid-lowering agents; of these, about 60% had low-density lipoprotein (LDL)
      cholesterol levels < 2.6 mmol/L. Among patients not treated with lipid-lowering
      agents, about 40% had LDL cholesterol levels < 2.6 mmol/L. Retinopathy was
      documented in 52% and 18%, and nephropathy in 9% and 36% of type 1 and type 2
      diabetes patients, respectively. CONCLUSIONS: Despite the demonstrated benefits
      of tight glucose, blood pressure and lipid control in reducing the risk of
      macrovascular and microvascular complications in type 1 and type 2 diabetes, our
      results suggest that treatment targets are not being met in a large proportion of
      patients attending a tertiary referral hospital. Responsible practice suggests
      that treatment targets and the current means to achieve them should both be
      examined.

PMID- 16999671
TI  - Implementing iron management clinical practice guidelines in patients with
      chronic kidney disease having dialysis.
AB  - OBJECTIVE: To evaluate the outcomes of and barriers to implementing standard
      guidelines (Caring for Australasians with renal impairment [CARI]), using iron
      management in patients having dialysis as an example. DESIGN AND SETTING: On-site
      review of iron management processes at six Australian dialysis units varying in
      size and locality. Patients' iron indices and haemoglobin levels were obtained
      from the Australian and New Zealand Dialysis and Transplant Registry.
      PARTICIPANTS: Patients with chronic kidney disease who were dependent on
      dialysis. MAIN OUTCOME MEASURES: Processes for assessing indices of iron stores
      and iron supplementation; comparison with target indices in the CARI guidelines.
      RESULTS: There was considerable variability among the units in achievement of
      haemoglobin and iron targets, with 25%-32% of patients achieving haemoglobin
      targets of 110-120 g/L, 30%-68% achieving ferritin targets of 300-800 microg/L,
      and 65%-73% achieving transferrin saturation targets of 20%-50%. Implementation
      barriers included lack of knowledge, lack of awareness of or trust in the CARI
      guideline, inability to implement the guideline, and inability to agree on a
      uniform unit protocol. Factors associated with achieving the CARI guideline
      targets included nurse-driven iron management protocols, use of an iron
      management decision aid, fewer nephrologists per dialysis unit, and a "proactive"
      (actively keeping iron levels within target range) rather than "reactive" (only
      reacting if iron levels are out of the range) protocol. CONCLUSIONS: Variability
      in achievement of iron targets, despite the availability of a clinical practice
      guideline, may be explained by variability in processes of care for achieving and
      maintaining adequate iron parameters.

PMID- 16999672
TI  - Suicide in the Northern Territory, 1981-2002.
AB  - OBJECTIVE: To examine trends in suicide in the Northern Territory between 1981
      and 2002, and demographic and other characteristics of people completing suicide
      in the Top End region in 2000-2002. DESIGN: Retrospective descriptive analysis of
      Australian Bureau of Statistics death registration data and data from the NT
      Coroner's Office. SETTING AND PARTICIPANTS: All residents of the NT who completed
      suicide between 1981 and 2002. MAIN OUTCOME MEASURES: Changes in the age-adjusted
      and age- and sex-specific rates of suicide in Indigenous and non-Indigenous NT
      residents over time; prior diagnosis of mental illness and use of alcohol or
      other drugs by those completing suicide. RESULTS: The age-adjusted suicide rate
      in the NT increased significantly between 1981 and 2002 (P < 0.001). Over this
      period, the rates among the Indigenous and non-Indigenous male populations
      increased by 800% (P < 0.05) and 30% (P > 0.05), respectively. Indigenous males
      aged under 45 years and non-Indigenous males aged 65 years and over were most at
      risk. In the Top End, a history of diagnosed mental illness was present in 49% of
      suicide cases, and misuse of alcohol or other drugs around the time of death was
      associated with 72% of suicide cases. CONCLUSION: Our study highlights the rising
      rate of suicide in the NT and suggests that suicide prevention initiatives need
      to specifically target Indigenous and non-Indigenous males in the age groups most
      at risk.

PMID- 16999673
TI  - Potential impact of AUSFTA on Australia's blood supply.
AB  - Australia is largely self-sufficient in its supply of safe, fresh blood products
      because of the goodwill of non-remunerated, volunteer donors, plus rigorous
      testing and processing standards. CSL Limited is the sole provider of plasma
      fractionation services in Australia, enjoying exclusive rights under the Plasma
      Fractionation Agreement with the Australian Government. In the Australia-United
      States Free Trade Agreement (AUSFTA), Australia agreed to review its current
      contract with CSL Limited, and to recommend to the states and territories that
      the process be opened up to overseas tender. Overseas tenders for off-shore
      fractionation services are likely to be highly competitive due to their low
      manufacturing costs and accumulated expertise. Off-shore fractionation could
      compromise the safety of Australia's blood supply through delays in processing
      and transportation, issues related to quality control, and even the siphoning of
      stock to overseas markets. This could compromise the long-term care of Australian
      patients and create a serious national security risk in the event of a terrorist
      attack or natural disaster. Australia's AUSFTA obligation to recommend changes
      does not equate to an obligation to actually proceed. The states and territories
      should carefully consider whether such changes would be in our national interest.
      The long-term security of the Australian people in the current security
      environment is dependent on continuance of an on-shore fractionation plant and
      appropriate back-up facilities.

PMID- 16999674
TI  - Should medical students be routinely offered BCG vaccination?
AB  - BCG vaccination is no longer routinely offered to all medical students in
      Victoria. Practices in Australia's 15 medical schools vary widely with respect to
      BCG vaccination and surveillance for tuberculosis (TB) infection during the
      medical course. Health care workers can be exposed to TB in Australian hospitals,
      but the risk is much higher if they undertake work in countries with a high
      prevalence of TB, such as during student electives. BCG vaccination is safe,
      cheap and protects 50% or more of recipients from active TB, including multidrug
      resistant TB. Protection is long-lasting, requires only a single dose, and there
      is new evidence that BCG may prevent primary infections, not just active disease.
      Although BCG vaccination interferes with the interpretation of the tuberculin
      skin test (TST), newer tests (QuantiFERON-TB Gold, T-SPOT.TB) are unaffected by
      BCG vaccination. We propose a standard approach for all Australian medical
      students that includes screening with TST and QuantiFERON-TB Gold/T-SPOT.TB at
      course entry, and recommending BCG vaccination for students who test negative,
      provided they have not previously received BCG vaccine.

PMID- 16999675
TI  - Inhalant misuse in youth: time for a coordinated response.
AB  - Early adolescence is associated with high rates of experimental inhalant misuse,
      but only a minority continue to inhale on a regular basis. Inhalant misuse is
      associated with a range of adverse outcomes, including reports of increased
      morbidity and mortality. Research into inhalant use among adolescents is lacking,
      with limited data available on long-term outcomes or evidence-based approaches to
      treatment. Legislative and supply-reduction strategies have been introduced by a
      number of states and territories over recent years, but direct funding for
      specific targeted interventions is lacking. Investment and commitment to a
      national research framework, as well as coordination of local services, is
      urgently required.

PMID- 16999676
TI  - Scurvy in an otherwise well young man.

PMID- 16999677
TI  - Infected atrial myxoma.

PMID- 16999678
TI  - 3. Drug hypersensitivity.
AB  - Most drug reactions are pharmacological reactions rather than hypersensitivity
      reactions. In assessing drug reactions, a detailed clinical history and careful
      documentation of reactions are most important. Elucidating the nature and time
      course (first versus subsequent exposure, immediate versus non-immediate) of a
      reaction can help to distinguish immune from non-immune hypersensitivity, as well
      as IgE-mediated from T cell-mediated allergy. Skin testing and in-vitro tests are
      of predictive value for only a limited group of IgE-mediated drug allergic
      reactions. Drug provocation challenges can be used to eliminate suspicion of a
      low-probability drug reaction, find a safe alternative to a proven or probable
      drug reaction, or as a means of desensitisation. If a patient taking an
      angiotensin-converting enzyme (ACE) inhibitor develops angioedema, the cause must
      be assumed to be the ACE inhibitor until proven otherwise.

PMID- 16999679
TI  - Latex allergy.

PMID- 16999680
TI  - A champion-driven pathway towards quality improvement in the medical management
      of osteoporotic fractures.

PMID- 16999681
TI  - Early medical abortion in Australia: more common than statistics suggest?

PMID- 16999682
TI  - Clinical trials of unapproved medicines in Australia.

PMID- 16999683
TI  - The repeating history of objections to the fortification of bread and alcohol:
      from iron filings to folic acid.

PMID- 16999684
TI  - Weight management in general practice: what do patients want?

PMID- 16999685
TI  - Production, purification and characterization of recombinant dengue multiepitope
      protein.
AB  - Dengue is an acute mosquito-borne viral disease of humankind. Dengue fever,
      dengue haemorrhagic fever and dengue shock syndrome have become global public
      health problems in recent years. rDME-G (recombinant dengue multiepitope protein
      that can specifically detect IgG) was produced in a 5-litre fermenter in
      Escherichia coli for use in diagnosis. The culture was induced with 1 mM
      isopropyl beta-D-thiogalactoside and cells were further grown for 4 h before
      harvesting. After fermentation, dry cell weight resulted in approx. 16.2 g/l. The
      rDME-G protein was purified from inclusion bodies using affinity chromatography.
      The final yield of purified rDME-G protein from fermentation resulted in approx.
      168 mg/l of pure biologically active rDME-G protein. The purity of rDME-G protein
      was checked by SDS/PAGE analysis and the reactivity of this protein was further
      determined by Western blotting. The purified protein was used to develop an in
      house dipstick ELISA and tested using a panel of 60 patient sera characterized
      using the commercially available tests for detection of dengue antibody. We
      compared our results with IgG-capture ELISA (Pan-Bio, Windsor, QLD, Australia)
      and rapid IC (immuno-chromatography) test (Pan-Bio). By using rDME-G protein as
      an antigen, in the dipstick ELISA, the results were in excellent agreement with
      commercial rapid IC test and IgG capture ELISA. These results show that the
      product has a promising potential to be used for diagnosis of dengue in both
      laboratory- and field-based detection systems with minimum cost and a high degree
      of sensitivity and specificity.

PMID- 16999686
TI  - Tax1-binding protein 1 is expressed in the retina and interacts with the GABA(C)
      receptor rho1 subunit.
AB  - Macromolecular signalling complexes that link neurotransmitter receptors to
      functionally and structurally associated proteins play an important role in the
      regulation of neurotransmission. Thus the identification of proteins binding to
      neurotransmitter receptors describes molecular mechanisms of synaptic signal
      transduction. To identify interacting proteins of GABA(C) (where GABA is gamma
      aminobutyric acid) receptors in the retina, we used antibodies specific for
      GABA(C) receptor rho1-3 subunits. Analysis of immunoprecipitated proteins by
      MALDI-TOF MS (matrix-assisted laser-desorption ionization-time-of-flight MS)
      identified the liver regeneration-related protein 2 that is identical with amino
      acids 253-813 of the Tax1BP1 (Tax1-binding protein 1). A C-terminal region of
      Tax1BP1 bound to an intracellular domain of the rho1 subunit, but not to other
      subunits of GABA(C), GABA(A) or glycine receptors. Confocal laser-scanning
      microscopy demonstrated co-localization of Tax1BP1 and rho1 in clusters at the
      cell membrane of transfected cells. Furthermore, Tax1BP1 and GABA(C) receptors
      were co-expressed in both synaptic layers of the retina, indicating that Tax1BP1
      is a component of GABA(C) receptor-containing signal complexes.

PMID- 16999687
TI  - Identification of a mitochondrial alcohol dehydrogenase in Schizosaccharomyces
      pombe: new insights into energy metabolism.
AB  - In the present study we have shown that mitochondria isolated from
      Schizosaccharomyces pombe exhibit antimycin A-sensitive oxygen uptake activity
      that is exclusively dependent on ethanol and is inhibited by trifluoroethanol, a
      potent inhibitor of ADH (alcohol dehydrogenase). Ethanol-dependent respiratory
      activity has, to our knowledge, not been reported in S. pombe mitochondria to
      date, which is surprising as it has been concluded previously that only one ADH
      gene, encoding a cytosolic enzyme, occurs in this yeast. Spectrophotometric
      enzyme assays reveal that ADH activity in isolated mitochondria is increased
      approximately 16-fold by Triton X-100, which demonstrates that the enzyme is
      located in the matrix. Using genetic knockouts, we show conclusively that the
      novel mitochondrial ADH is encoded by adh4 and, as such, is unrelated to ADH
      isoenzymes found in mitochondria of other yeasts. By performing a modular-kinetic
      analysis of mitochondrial electron transfer, we furthermore show how ethanol
      dependent respiratory activity (which involves oxidation of matrix-located NADH)
      compares with that observed when succinate or externally added NADH are used as
      substrates. This analysis reveals distinct kinetic differences between substrates
      which fully explain the lack of respiratory control generally observed during
      ethanol oxidation in yeast mitochondria.

PMID- 16999688
TI  - The relation between mitral annular calcification and mortality in patients
      undergoing diagnostic coronary angiography.
AB  - To determine whether the observed association between mitral annular
      calcification (MAC) and mortality is independent of the severity of coronary
      artery disease (CAD), we analyzed data from 134 male veterans (age 63 +/- 10
      years) followed for 5 years who had undergone diagnostic coronary angiography and
      transthoracic echocardiography within 6 months of each other. Echocardiograms
      were retrospectively reviewed for the presence of MAC. The relation of MAC to all
      cause mortality was analyzed using logistic regression, and odds ratios (OR) were
      calculated. MAC was present in 49 (37%) subjects. Over the 5-year follow-up
      period, 38 (28%) patients expired. Five-year survival was 80% for subjects
      without MAC and 56% for subjects with MAC (P = 0.003). MAC (OR = 3.16, 95%
      confidence interval [CI]= 1.43-6.96, P = 0.003), ejection fraction (OR = 0.76,
      95% CI = 0.59-0.97, P = 0.02), and left main CAD (OR = 2.70, 95% CI = 1.11-6.57,
      P = 0.02) were significantly associated with mortality in univariate analysis.
      After adjusting for left ventricular ejection fraction, number of obstructed
      coronary arteries and the presence of left main coronary artery stenosis, MAC
      significantly predicted death (OR = 2.48, 95% CI = 1.09-5.68, P = 0.03).
      Similarly, after adjusting for predictors of MAC, including ejection fraction,
      age, diabetes, peripheral vascular disease, and heart failure, MAC remained a
      significant predictor of death (OR = 2.38, 95% CI = 1.02-5.58, P = 0.04). MAC
      also predicted death independent of smoking status, hypertension, serum
      creatinine, low density lipoprotein cholesterol, high density lipoprotein
      cholesterol, and C-reactive protein levels (OR = 3.98, 95% CI = 1.68-9.40, P =
      0.001). MAC detected by two-dimensional echocardiography independently predicts
      mortality and may provide an easy-to-perform and inexpensive way to improve risk
      stratification.

PMID- 16999689
TI  - Left and right ventricular function is impaired in Behcet's disease.
AB  - OBJECTIVES: Subclinical cardiac involvement may occur in patients with Behcet's
      disease (BD). The purpose of our study was to assess the noninvasive parameters
      of biventricular function derived from Doppler tissue imaging (DTI) of the
      tricuspid and mitral annular motion in BD. METHODS: Twenty-one patients with BD
      and 20 control subjects were enrolled in this study. All subjects were selected
      to exclude those with cardiovascular risk factors. Standard echocardiography and
      pulsed DTI were obtained in every patient. RESULTS: Peak systolic (13.71 +/- 2.09
      vs 20.01 +/- 1.57, P < 0.001), peak early diastolic (11.26 +/- 2.52 vs 15.35 +/-
      2.06, P < 0.001) tricuspid annular velocities were significantly lower in
      patients than controls. Peak systolic (8.68 +/- 1.4 vs 12.25 +/- 1.7, P < 0.001),
      peak early diastolic (7.89 +/- 1.07 vs 9.94 +/- 1.12, P < 0.001), and peak end
      diastolic (8.30 +/- 1.32 vs 9.23 +/- 0.91, P = 0.013) lateral mitral annular
      velocities were significantly lower in patients than controls. CONCLUSIONS: We
      demonstrated that myocardial velocities, were affected in patients with BD.
      Therefore, we conclude that right and left ventricular function is impaired in
      patients with BD.

PMID- 16999690
TI  - Incidence of pericardial effusion in females stimulated in "in vitro
      fertilization" program.
AB  - AIMS: To evaluate the incidence of pericardial irritation in females after
      hormonal stimulation in in vitro fertilization program, and to set its clinical
      significance as a symptom of ovarian hyperstimulation syndrome (OHSS). PATIENTS:
      Thirty-nine females, aged 30 +/- 5 years (20-46), with a normal echo finding
      prior to hormonal stimulation. METHODS: Serial echocardiography: baseline A, in
      hCG application B, embryo-transfer C. RESULTS: Thirty-nine, 39, and 35
      echocardiography examinations were done on A, B, and C respectively. On B, in 7
      (17.9%) of 39 patients either new pericardial effusion "1," increased pericardial
      echogenicity "2," or both "3" were detected (4 patients, 2 patients, and 1
      patient, i.e., 10.3%, 5.1%, and 2.6% respectively.). On C, in 8 of 35 patients
      (22.8 %) abnormalities were detected: "1" in 2 patients (5.7 %), "2" in 1 patient
      (2.9 %), and "3" in 5 patients (14.2 %). No clinical symptoms related to these
      findings were present. No OHSS occurred in these patients. On the contrary,
      clinical OHSS developed later in 2 patients, classified as medium degree (1
      patient) and severe degree (1 patient)-both patients had negative echo during
      follow-up. CONCLUSION: Echocardiographic signs of mild pericardial irritation may
      appear also in patients with no clinical signs of OHSS. The incidence of these
      changes increases during stimulation procedure. Development of OHSS may not be
      preceded by the incidence of these warning signs. Consequently, routine
      echocardiographic examination during stimulation is not indicated, since
      significant pericardial effusion is rather a late sign of OHSS.

PMID- 16999691
TI  - Relationship between outflow obstruction and left ventricular functional
      impairment in hypertrophic cardiomyopathy: a Doppler echocardiographic study.
AB  - Left ventricular outflow tract (LVOT) obstruction is predictive of a worse
      outcome in hypertrophic cardiomyopathy (HCM). In a detailed Doppler
      echocardiographic study of 178 selected HCM patients, the group of patients (n =
      73) with the obstructive form (resting peak gradient > or = 30 mmHg) presented
      more hypertrophy and poorer systolic and diastolic left ventricular (LV)
      functions than the HCM group (n = 105) without obstruction. LVOT peak gradient
      was positively correlated with hypertrophy (P < 0.0001) and negatively to tissue
      Doppler mitral annulus systolic (P = 0.0001) and early diastolic (P < 0.0001)
      velocities. The gradient significantly correlated with E/Ea ratio (r = 0.67; P <
      0.0001). By multiple regression, LVOT gradient was related to E/Ea, LV maximal
      thickness and left atrial size. In comparison with patients without obstruction,
      patients with obstruction presented greater hypertrophy (P < 0.0001), lower
      systolic and early diastolic mitral annulus velocities (both P < 0.0001), higher
      E/Ea ratio (P < 0.0001) and higher global function index (P < 0.0001). In HCM,
      beyond the effects on hypertrophy, LVOT obstruction is an independent determinant
      of LV functional abnormalities.

PMID- 16999692
TI  - Detection of patency of internal mammary artery grafts to the left anterior
      descending artery by transthoracic Doppler echocardiography.
AB  - BACKGROUND: To determine whether a coronary artery bypass graft (CABG) is patent,
      we examined the flow of the left internal mammary artery (LIMA) to the left
      anterior descending artery (LAD) by transthoracic Doppler echocardiography
      (TTDE). PATIENTS AND METHODS: Eighty-seven patients with CABG (LIMA to distal
      LAD) were enrolled in the study. The flows from each subject were analyzed by
      three criteria: mosaic flow at the anastomosis site, distal anterograde flow
      (ante flow), and proximal retrograde flow (retro flow). RESULTS: On angiography,
      79 grafts were patent and eight were not. TTDE study of 79 patent grafts
      demonstrated mosaic, ante, and retro flow in 63 (79.7%), 74 (93.7%), and 35
      grafts (49.4%), respectively. The averaged diastolic peak velocity of ante flow
      was 26.3 +/- 11.0 cm/sec, significantly higher than that (4.8 +/- 7.1 cm/sec, P <
      or = 0.0001) in eight patients without patent grafts. These eight patients had no
      mosaic or retro flow and only three had ante flow. The accuracies to predict
      patency were 81.6%, 90.8%, and 49.4% for mosaic, ante, and retro flows,
      respectively. CONCLUSIONS: The existence of mosaic, retro, or sufficient ante
      flows strongly indicated the patency of LIMA to the LAD. When symptoms are
      possible to be derived from the occlusion of CABG to LAD, TTDE is a promising
      method to examine whether a LIMA to LAD bypass is patent.

PMID- 16999693
TI  - Tricuspid annular systolic velocity: a useful measurement in determining right
      ventricular systolic function regardless of pulmonary artery pressures.
AB  - Assessment of right ventricular (RV) systolic function can be somewhat difficult,
      particularly in pulmonary hypertension (PH). RV fractional area change (FAC) and
      tricuspid valve annular motion (TAPSE) although useful in the assessment of RV
      performance, their use can be sometimes limited and tedious. Thus, a quicker but
      yet reliable alternative is needed. Accordingly, we compared peak tricuspid
      annulus systolic (TA Sa) velocities derived from Doppler tissue imaging (DTI)
      with both RVFAC and TAPSE to estimate RV function in 52 patients (53 +/- 16
      years) with varying degrees of PH. In this group, mean was RVFAC 49 +/- 20, TAPSE
      was 2.3 +/- 0.7 cm, peak TA Sa velocity by DTI was 10.4 +/- 3.8 cm/s, left
      ventricular systolic function was 57 +/- 18%, and pulmonary artery systolic
      pressure was 47 +/- 28 mmHg. An excellent correlation was noted between TAPSE and
      RVFAC (r = 0.91, P < 0.001). Similar correlations were noted between peak TA Sa
      velocity and RVFAC (r = 0.84, P < 0.001) and between peak TA Sa velocity and
      TAPSE (r = 0.90, P < 0.001). A TA Sa >10.5 cm/s identified individuals with both
      a normal RV function and without significant PH. Therefore, we conclude that TA
      Sa velocity, an easily obtainable DTI measure, that has an excellent correlation
      with more time-consuming methods to assess RV systolic function regardless of the
      degree of PH should be routinely assessed during the initial evaluation and
      eventual follow-up of patients either at risk or with documented PH.

PMID- 16999694
TI  - Evaluation of the electrocardiographic criteria for left ventricular hypertrophy
      with use of three-dimensional echocardiography.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is a common condition that carries
      an increased risk of cardiovascular events. Use of ECG in detection of LVH is
      limited because of the reported low sensitivity. Conventional echocardiographic
      techniques used as the standard for estimating left ventricular (LV) mass have
      limitations related to the position of the image plane and shape of the
      ventricle. Three-dimensional echocardiography is free of these limitations and
      therefore is more accurate. We hypothesized that accuracy of ECG criteria for LVH
      would improve when LV mass was assessed by three-dimensional echocardiography.
      RESULTS: For most of the criteria, sensitivity, specificity and accuracy improved
      when LV mass was assessed by three-dimensional echocardiography. Two-dimensional
      echocardiography significantly overestimated LV mass as compared with the three
      dimensional method. CONCLUSIONS: Sensitivity, specificity, and accuracy of the
      ECG criteria improved when LV mass was estimated by three-dimensional
      echocardiography. This improvement may be attributed at least in part to superior
      accuracy of three-dimensional measurements.

PMID- 16999695
TI  - Real time three-dimensional transthoracic echocardiography for guiding Amplatzer
      septal occluder device deployment in patients with atrial septal defect.
AB  - BACKGROUND: Transcatheter Amplatzer septal occluder (ASO) device closure of
      atrial septal defects (ASDs) has traditionally been guided by two-dimensional
      transesophageal echocardiography (2D-TEE) and intracardiac echocardiography (ICE)
      modalities. Real time three-dimensional transthoracic echocardiography (RT3D-TTE)
      provides rotating images to define ASD and adjacent structures with potential as
      an alternative to 2D-TEE or ICE for guiding the device closure of ASD. Our aim
      was to assess the feasibility and effectiveness of RT3D-TTE in parasternal four
      chamber views to guide ASO device closure of ASD. METHODS AND RESULTS: From July
      2004 to August 2005, 59 patients underwent transcatheter ASO device closure of
      ASD. The first 30 patients underwent 2D-TEE guidance under general anesthesia and
      the remaining 29 patients underwent RT3D-TTE guidance with local anesthesia. All
      interventions were successfully completed without complications. The clinical
      characteristics and transcatheter closure variables of RT3D-TTE and 2D-TEE were
      compared. Echocardiographic visualization of ASD and ASO deployment was found to
      be adequate when using either methods. Catheterization laboratory time (39.1 +/-
      5.4 vs 78.8 +/- 14.1 minutes, P < 0.001) and interventional procedure length (7.6
      +/- 4.2 vs 15.3 +/- 2.9 minutes, P < 0.001) were shortened by using RT3D-TTE as
      compared with 2DE-TEE. There was no difference in the rate of closure following
      either method, assessed after a 6-month follow-up. The maximal diameter measured
      by RT3D-TTE and 2D-TEE was correlated well with a balloon-stretched ASD size (y =
      0.985x + 0.628, r = 0.924 vs y = 0.93x + 2.08, r = 0.885, respectively).
      CONCLUSION: RT3D-TTE may be a feasible, safe, and effective alternative to the
      standard practice of using 2D-TEE to guide ASO deployment.

PMID- 16999696
TI  - Echocardiographic evaluation of mitral valve repair by modified "edge to edge"
      technique.
AB  - The "edge to edge" or "double-orifice" technique is an alternative surgical
      option of mitral valve repair to treat mitral regurgitation. Echocardiography is
      very useful to evaluate the postoperative valve function, but since this
      technique is not frequently used, there is little experience about its
      echocardiographic features, which are different from those of the classic mitral
      valve repair. In this report, we present a patient who underwent this repair with
      a modified approach called "triple-orifice technique" and was evaluated by
      transthoracic and transesophageal echocardiography.

PMID- 16999697
TI  - Prosthetic valve thrombosis presenting as an acute embolic myocardial infarction
      in a pregnant patient: issues on anticoagulation regimens and thrombolytic
      therapy.
AB  - Mechanical valves are inherently thrombogenic and require meticulous
      anticoagulation. Pregnancy produces a hypercoagulable state and achieving
      adequate anticoagulation is difficult. We present a pregnant patient who had a
      nonobstructive thrombus of mechanical mitral valve causing embolic acute
      myocardial infarction. Issues surrounding management of anticoagulation and use
      of thrombolytic therapy during pregnancy are discussed. Education regarding the
      critical nature of adequate anticoagulation in these patients is important.

PMID- 16999698
TI  - Progress of untreated massive cardiac echinococcosis--echocardiographic follow
      up.
AB  - A 56-year-old man was admitted with chest pain and dyspnea. Echocardiographic
      evaluation revealed a giant cystic cardiac mass with multiple loculations at
      interventricular septum extended to inferoposterior region protruding inside the
      cavity. The patient refused surgical therapy. His complaints persisted without
      significant changes after 5 months. Second echocardiographic evaluation revealed
      conjugation of previous multiple cyst to gigantic intramyocardial cyst and
      minimal pericardial effusion. We intend to illustrate herein an unusual
      echocardiographic appearance and progress of an untreated massive "cardiac
      echinococcosis." If cardiac hydatid cyst is left untreated it may transform to
      large cavity with a high risk of rupture.

PMID- 16999699
TI  - Congenital partial pericardial defect and herniated right atrial appendage: a
      rare anomaly.
AB  - A congenital partial defect of the right-sided pericardium is a rare cardiac
      anomaly and it represents defective formation of the pleuropericardial membrane.
      Patients can be asymptomatic, but they may experience chest pain, myocardial
      ischemia, emboli, arrhythmia, and sudden death. In this report, we present an 8
      month-old boy with pericardial defect and right atrial appendage herniation. It
      was diagnosed by echocardiography and cardiac magnetic resonance imaging.

PMID- 16999700
TI  - Congenital right ventricular diverticulum associated with a ventricular septal
      defect: a rare echocardiographic finding.
AB  - A neonate presented on the first day of life with tachypnea and poor feeding. The
      infant's initial echocardiogram demonstrated outpouching of the lateral wall of
      the right ventricle (RV) associated with a large ventricular septal defect (VSD).
      At 9 days of age he was diagnosed with osteogenesis imperfecta (OI). Despite
      treatment with digoxin, diuretics, and captopril he required hospitalization
      twice during his first 2 months of life for congestive heart failure (CHF). The
      VSD was closed at three and one-half months of age without resection of the
      diverticulum and CHF symptoms resolved. At 26 months of age he is doing well
      despite the residual RV diverticulum. Congenital cardiac diverticula are rare
      forms of cardiac malformations and their echo-Doppler features are herein
      discussed.

PMID- 16999701
TI  - Transesophageal echocardiography through nasal way as a guide to percutaneous
      closure of patent foramen ovale.
AB  - Percutaneous device closure of patent foramen ovale (PFO) has become an effective
      and safe alternative to medical or surgery treatment. Transesophageal
      echocardiography (TEE), as commonly used to guide this procedure, has the
      limitation to require general anesthesia. Recently, intracardiac echocardiography
      (ICE) with AcuNav probe was used to guide percutaneous PFO closure. We report a
      42 year-old man with two previous cryptogenetic strokes in whom both diagnosis
      and guidance of PFO closure were performed by means of TEE using the AcuNav
      catheter introduced through nasal way (TEENW). This technique, that does not
      require general anesthesia, provided adequate and complete view of the Amplatzer
      procedure. TEENW might offer a feasible and equivalent echocardiographic
      alternative either to standard TEE or ICE as a guide to percutaneous PFO closure.

PMID- 16999702
TI  - Quantification of tricuspid regurgitation by live three-dimensional transthoracic
      echocardiographic measurements of vena contracta area.
AB  - We evaluated tricuspid regurgitation (TR) by multiple echocardiographic
      techniques in 93 consecutive patients who underwent standard two-dimensional (2D)
      and live three-dimensional (3D) transthoracic echocardiography (TTE). TR vena
      contracta (VC) area was obtained by 3D TTE by systematic and sequential cropping
      of the acquired 3D TTE dataset. Assessment of VC area by 3D TTE was compared to
      2D TTE measurements of the ratio of TR regurgitant jet area to right atrial area
      (RJA/RAA), RJA alone, VC width, and calculated VC area. VC area from 3D TTE
      closely correlated with RJA/RAA and RJA alone as determined from 2D TTE
      measurements. Live 3D TTE color Doppler measurements of VC area can be used for
      quantitative assessment of TR and offer incremental value for quantification of
      particularly severe regurgitant lesions.

PMID- 16999703
TI  - Cor triatriatum sinister: assessment by live/real time three-dimensional
      transthoracic echocardiography.
AB  - We report a 49-year-old morbidly obese female with a poor acoustic window in whom
      live/real time three-dimensional transthoracic echocardiography was able to make
      a confident diagnosis of cor triatriatum sinister. En face views of the membrane
      facilitated accurate assessment of the size and shape of the large nonobstructing
      opening in the membrane. Maximum dimensions of the opening were 3.06 x 1.03 cm
      and area was 2.3 cm(2).

PMID- 16999704
TI  - Incompetence of the internal jugular venous valve: spectrum of echo-Doppler
      appearances.
AB  - The echocardiographic literature contains very scant reference to incompetence of
      the valve in the internal jugular vein. However, we found frequent Doppler
      evidence of such incompetence, especially in patients with congestive failure.
      This incompetence manifests as a variety of color Doppler and pulsed Doppler
      patterns, illustrated here in 3 patients.

PMID- 16999705
TI  - Cardiac echinococcosis.

PMID- 16999706
TI  - Diagnosis of an anatomically and physiologically significant patent foramen
      ovale.

PMID- 16999708
TI  - Who are you in the schools?

PMID- 16999709
TI  - An overview of ethnicity and assessment of family history in primary care
      settings.
AB  - PURPOSE: To discuss the importance of and the nurse practitioner's (NP's) role in
      the assessment of ethnicity/family of origin in conducting a multigenerational
      family history in primary care settings. DATA SOURCES: A review of the literature
      on past research results addressing racial and ethnic disparities and current
      articles from scientific journals exploring the relationship between race and
      genetics. Web sites were from the National Institutes of Health, the Human Genome
      Research Institute, the National Cancer Institute, and the Health and Human
      Services Minority Health and Disparities report. CONCLUSIONS: The family history
      has received renewed interest due to the sequencing of the human genome. A
      multigenerational family history is an important first step in screening for a
      multitude of disorders impacted by genetic susceptibility, shared environments,
      and common behaviors. Assessment of the patient's ethnicity/family of origin is
      an integral part of the multigenerational family history, particularly in the
      diagnosis of chronic diseases and the assessment of risks for genetic disorders.
      The multigenerational family history is important in diagnosis, predictive
      genetic testing, disease prevention, and health promotion. Challenges facing NPs
      and the utilization of a multigenerational family history in the current U.S.
      health system include (a) training clinicians on the correct assessment and
      utilization of a multigenerational family history, (b) assessment of the
      subtleties of ethnicity and identifying multiple ethnic groups within a family,
      (c) collection of the family history in a manner that is sensitive to the
      cultural beliefs of individuals, and (d) avoidance of stereotyping. IMPLICATIONS
      FOR PRACTICE: Significant advances in genetics and genetic testing requires that
      NPs be well versed in collecting and interpreting a multigenerational family
      history to include assessment of the patient/family's ethnicity/family of origin.
      The ability to effectively conduct and evaluate the individual's and family's
      health risk through a multigenerational family history will be important in
      diagnosis, health promotion, disease prevention, and the determination for
      genetic counseling referral and predictive testing when appropriate. Assessment
      of risk and prevention of disease is also important in reducing health
      disparities.

PMID- 16999710
TI  - Medicare Part D: practical practice information for healthcare providers.
AB  - PURPOSE: To provide an overview of Medicare Part D and useful practice
      information for healthcare providers to help guide Medicare beneficiaries when
      choosing a Part D plan. DATA SOURCES: Documents written by the Centers for
      Medicare & Medicaid Services, Kaiser Family Foundation, and United States
      Department of Health & Human Services. CONCLUSIONS: Although Medicare Part D can
      provide assistance with prescription drug costs to Medicare beneficiaries, the
      transition to Medicare Part D in 2006 will be challenging for both beneficiaries
      and healthcare providers. It is important that both Medicare beneficiaries and
      healthcare providers understand the complex drug benefit to facilitate the
      transition to Medicare Part D. IMPLICATIONS FOR PRACTICE: It is likely that
      Medicare Part D formularies will require adjustments to many Medicare
      beneficiaries' medication regimens. Additionally, it is possible that there will
      be an increase in the number of prior authorizations and other requirements such
      as step therapy requests.

PMID- 16999711
TI  - Beta-blocker medication usage in older women after myocardial infarction.
AB  - PURPOSE: The purpose of this study was to assess demographic characteristics of
      women prescribed beta-blocker (beta-blocker) medication and compare to those not
      using beta-blocker medication, and to determine if there are differences in
      depression and fatigue among women who used beta-blockers compared to nonusers 6
      12 months after myocardial infarction (MI). DATA SOURCES: This was a descriptive
      cross-sectional study of 84 women (61 using beta-blockers and 23 not using beta
      blockers) aged 65 and older who were 6-12 months post-MI. Women had their height
      and weight measured and completed a Demographic Health Form, the Geriatric
      Depression Scale, and the Revised Piper Fatigue Scale (RPFS). CONCLUSIONS: While
      most of the women were taking beta-blockers after MI (74%), significantly fewer
      Black women were taking beta-blockers (chi(2) = 5.086, p = 0.032). Most of the
      beta-blocker users were overweight or obese. There were no significant
      differences in age, t(82) = 0.7, p = 0.486; body mass index, t(82) = 0.76, p =
      0.445; income, chi(2)(df = 2) = 3.219, p = 0.075; mean depression, t(82) = 1.648,
      p = 0.103; or fatigue scores, t(82) = 0.993, p = 0.324, between beta-blocker
      users and nonusers. More of those not taking beta-blockers reported fatigue with
      significantly higher fatigue in the affective meaning dimension of the RPFS,
      t(82) = 2.272, p = 0.03. IMPLICATIONS FOR PRACTICE: beta-Blocker medication
      continues to be underutilized in older women. Because no difference was noted in
      fatigue and depression in the two groups, these may mean that these side effects
      are not barriers in prescribing this medication post-MI. Nurse practitioners are
      in pivotal positions to monitor the ongoing physiological and psychological
      sequelae post-MI and implement interventions to improve their outcomes.

PMID- 16999712
TI  - Health behaviors in breast cancer survivors experiencing bone loss.
AB  - PURPOSE: To describe the baseline healthy lifestyle behaviors (dietary, calcium,
      vitamin D, caffeine and alcohol intake, smoking history, and physical activity)
      of postmenopausal breast cancer survivors (BCS); and to identify any relationship
      of healthy lifestyle behaviors with bone mineral density (BMD) at the forearm,
      total hip and spine, L1-L4. DATA SOURCES: Self-reported responses to a
      demographic and health status questionnaire, to a 3-day Diet Record, and to the 7
      Day Physical Activity Questionnaire-Adapted provided data for the lifestyle
      behaviors. Baseline BMD (g/cm(2)) was determined with dual-energy x-ray
      absorptiometry (DEXA). Height, weight, and body mass index (BMI) were also
      measured in each of the 249 postmenopausal BCS. CONCLUSIONS: There was an
      imbalance between consumed kilocalories and expenditure of energy. The majority
      of BCS were overweight or obese. They consumed less fruit and vegetable servings
      than recommended by the new 2005 U.S. Department of Agriculture's dietary
      guidelines, less dairy products, below average recommended grains and fiber, less
      protein and carbohydrate intake, and a slightly higher fat gram intake.
      Approximately, 43% did not take any supplemental calcium, with 46% taking less
      than 1000 mg a day. Likewise, 52.59% consumed less than 400 IU of vitamin D with
      both supplemental and dietary intake. This group of BCS consumed below accepted
      levels of caffeine and alcohol. Only 18 BCS continued to smoke. This group spent
      an average of 10.36 h in light (sedentary) activities on a daily basis. There
      were significant negative relationships with bone mass (g/cm(2)) at the total hip
      and daily intake of caffeine/mg and daily grams of alcohol. Weight and BMI both
      demonstrated a significant relationship with bone mass (g/cm(2)) at the total
      hip, spine L1-L4, and the forearm. IMPLICATIONS FOR PRACTICE: The healthcare
      provider must incorporate appropriate teaching strategies, intensive counseling,
      and coaching, along with a support mechanism, to enable BCS to understand the
      importance of a healthy diet, calcium, and vitamin D supplement, and a regular
      strength/weight program that will be integrated into their daily lifestyle. Early
      DEXA screens should be part of the protocol with BCS, and there is a particular
      need for forearm DEXA screens to be included in the treatment protocol for BCS.

PMID- 16999713
TI  - Reconsidering the effects of monosodium glutamate: a literature review.
AB  - PURPOSE: This article reviews the literature from the past 40 years of research
      related to monosodium glutamate (MSG) and its ability to trigger a migraine
      headache, induce an asthma exacerbation, or evoke a constellation of symptoms
      described as the "Chinese restaurant syndrome." DATA SOURCES: Literature
      retrieved by a search using PubMed, Medline, Lexis-Nexus, and Infotrac to review
      articles from the past 40 years. CONCLUSIONS: MSG has a widespread reputation for
      eliciting a variety of symptoms, ranging from headache to dry mouth to flushing.
      Since the first report of the so-called Chinese restaurant syndrome 40 years ago,
      clinical trials have failed to identify a consistent relationship between the
      consumption of MSG and the constellation of symptoms that comprise the syndrome.
      Furthermore, MSG has been described as a trigger for asthma and migraine headache
      exacerbations, but there are no consistent data to support this relationship.
      Although there have been reports of an MSG-sensitive subset of the population,
      this has not been demonstrated in placebo-controlled trials. IMPLICATIONS FOR
      PRACTICE: Despite a widespread belief that MSG can elicit a headache, among other
      symptoms, there are no consistent clinical data to support this claim. Findings
      from the literature indicate that there is no consistent evidence to suggest that
      individuals may be uniquely sensitive to MSG. Nurse practitioners should
      therefore concentrate their efforts on advising patients of the nutritional
      pitfalls of some Chinese restaurant meals and to seek more consistently
      documented etiologies for symptoms such as headache, xerostomia, or flushing.

PMID- 16999714
TI  - Evidence-based practice: review of clinical evidence on the efficacy of
      glucosamine and chondroitin in the treatment of osteoarthritis.
AB  - PURPOSE: To evaluate past and current evidence from randomized controlled trials
      on the efficacy of glucosamine sulfate (GS), glucosamine hydrochloride (GH), and
      chondroitin sulfate (CS) for the treatment of osteoarthritis (OA). DATA SOURCES:
      An extensive review of four meta-analyses and a review of the findings of the
      recently published Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)
      funded by the National Institutes of Health. FINDINGS: Review of previous studies
      on the efficacy of GS, GH, and CS in the treatment of OA showed inconclusive
      results because of weak research design. The GAIT attempted to provide clarity on
      the use of GH and CS in treating knee pain from OA by using a rigorous research
      design to elicit cause and effect. The GAIT results showed that GH and CS were
      not effective in reducing knee pain in the study group overall; however, these
      may be effective in combination for patients with moderate-to-severe knee pain.
      IMPLICATIONS FOR PRACTICE: There is now clinical evidence indicating that
      recommending GS, GH, and CS for the treatment of mild knee pain from OA is
      ineffective. Further research needs to be done to identify specific
      characteristics in patients that results in a positive response. Until the
      findings of the GAIT undergo further peer review, the results of the research
      needs to be interpreted with caution.

PMID- 16999715
TI  - Safety of live-virus vaccines for children with immune deficiency.
AB  - PURPOSE: Conduct an integrative literature review to evaluate the safety and
      effectiveness of live-virus vaccines, namely, the measles, mumps, rubella, and
      varicella vaccines, in children who are immune compromised by exogenous
      medication either posttransplant or while undergoing maintenance chemotherapy for
      leukemia. DATA SOURCES: Medline, MedlinePlus, EBSCO, PubMed, MD Consult, CINAHL,
      Clinical Pharmacology, ERIC, Biomedical Reference Collection-Basic, Health Source
      Consumer Edition, Health Source-Nursing/Academic Edition, Ovid, CANCERLIT, and
      the Cochrane Library Online. CONCLUSIONS: Because measles infection has a low
      incidence rate in the United States, it may be advisable not to vaccinate
      children who are immunocompromised and risk side effects of the vaccine. In
      contrast to measles infection, varicella has a higher incidence rate and poses a
      more imminent threat to those who are immunocompromised. Children who are
      immunosuppressed can receive the varicella vaccination; however, they should have
      regular titers drawn to confirm adequate protection against the disease and
      should receive boosters as deemed appropriate. IMPLICATIONS FOR PRACTICE: The
      number of solid organ transplant recipients is steadily increasing with more than
      600,000 solid organ transplantations worldwide since the first renal transplant
      in 1954. The steadily increasing numbers of pediatric patients surviving
      transplantation, coupled with increased life expectancy, accelerate the need for
      nurse practitioners to understand the management of these delicate patients
      following release from the transplant unit.

PMID- 16999717
TI  - Prevalence, consequences and prevention of childhood nutritional iron deficiency:
      a child public health perspective.
AB  - The true extent of nutritional iron deficiency (ID) in childhood is unclear
      because of uncertainty over its definition and the insensitivity of markers of
      ID. The major cause is likely to be the excessive and early use of cow's milk.
      Recent neurophysiological observations support the many field studies correlating
      ID with cognitive developmental delays. Prevention is best sought through
      supplementation of essential foods.

PMID- 16999718
TI  - Hospital admissions for acute painful crisis in Trinidad and Tobago. Are the
      British Committee for Standards in Haematology (BCSH) guidelines applicable?
AB  - We observed consecutive hospital admissions for acute painful crisis (APC) among
      adults with Sickle Cell Disease (SCD) over a 6-month period in Trinidad and
      Tobago. Episodes (111) of APC resulted in 82 admissions of 59 patients. The most
      common site for pain was the trunk. Patients ranged in age from 17 to 53 years
      (median: 25). Median length of hospital stay was 4 days. Total dose of Pethidine
      given per admission ranged from 100 to 1650 mg (median: 525). The mean dose of
      morphine was 70 mg. Six (7%) of patients were readmitted within 10 days of
      discharge. Twenty-five (30%) of patients had chest pain at presentation of whom
      10 (12%) had consolidation on chest X-ray, defining the acute chest syndrome
      (ACS). There was one death caused by biliary sepsis. The study revealed seemingly
      low opiate usage for in-hospital treatment of APC with acceptable rates of
      readmission. The BCSH 2003 guidelines seemed applicable apart for the choice and
      route of fluid for rehydration and opiate analgesia.

PMID- 16999719
TI  - Reticulocyte hemoglobin equivalent (Ret He) and assessment of iron-deficient
      states.
AB  - Direct measurement of the reticulocyte hemoglobin content provides useful
      information for the diagnosis and treatment of iron-deficient states. We have
      examined direct measurements of reticulocyte and red cell hemoglobin content on
      the Sysmex XE 2100 (Ret He and RBC He respectively) and the Bayer ADVIA 2120 (CHr
      and CH respectively) analyzers. Good agreement was found between Ret He and CHr
      (Y = 1.04X - 1.06; r2= 0.88) and between the RBC He and CH parameters (Y = 0.93X
      + 1; r2= 0.84 n = 200) in pediatric patients and in normal adults (Ret He and
      CHr; Y = 1.06X - 0.43; r2= 0.83; n = 126; RBC He and CH; Y = 0.94X + 1; r2= 0.87;
      n = 126). In 1500 blood samples from patients on chronic dialysis, Ret He was
      compared with traditional parameters for iron deficiency (serum iron <40
      microg/dl, Tsat <20%, ferritin <100 ng/ml, hemoglobin <11 g/dl) for identifying
      iron-deficient states. Receiver operator characteristic (ROC) curve analysis
      revealed values of the area under the curve for Ret He of 0.913 (P < 0.0001).
      With a Ret He cutoff level of 27.2 pg, iron deficiency could be diagnosed with a
      sensitivity of 93.3%, and a specificity of 83.2%. Ret He is a reliable marker of
      cellular hemoglobin content and can be used to identify the presence of iron
      deficient states.

PMID- 16999720
TI  - Recombinant factor VIIa: unregulated continuous use in patients with bleeding and
      coagulopathy does not alter mortality and outcome.
AB  - Recombinant factor VIIa (rFVIIa) is used in patients with hemophilia who had
      developed inhibitors. A hemostatic effect has been demonstrated following the
      administration of rFVIIa in patients after trauma and bleeding. Currently, there
      is no widely accepted guideline for off-label rFVIIa usage in bleeding patients.
      We planned to review the rFVIIa utilization practice in our institution and
      develop policies and guidelines for future rFVIIa use. We acquired the medical
      records of 55 patients who received rFVIIa at our institution during 2003-2004.
      Patient charts were reviewed regarding their rFVIIa administration and
      indications, dose and frequency, cost, pre-rFVIIa blood component usage,
      utilization of hematology services and outcome were analyzed. Underlying liver
      disease with coagulopathy was the commonest (47%) indication for rFVIIa use.
      Recombinant FVIIa was successful (69%) in correcting laboratory parameters of
      coagulopathy, but did not alter outcome. Twenty-six of the 55 patients (47%) died
      during the same admission from their underlying diseases. Apart from two trauma
      patients, no one died from bleeding. We conclude that unregulated continuous
      administration of rFVIIa in bleeding/coagulopathic patients did not alter
      outcome. Closer monitoring of rFVIIa usage, including hematology consultation and
      enforcement of pre-rFVIIa blood component usage would optimize cost
      effectiveness.

PMID- 16999721
TI  - The relation between plasminogen activator inhibitor activity and disease
      activation in acute myeloblastic leukaemia patients.
AB  - Coagulation and fibrinolytic abnormalities are common in patients with acute
      myeloblastic leukaemia (AML) like other forms of leukaemias. In this study, we
      investigated if total plasminogen activator inhibitor (PAI) activity, which is
      believed to increase in initial diagnosis and relapse in AML patients could be
      accepted as a relapse criterion or not. Total of 34 AML patients and 18 healthy
      volunteers were included in this study. The patients' diagnosis were based on
      clinical criteria as well as morphological, cytochemical, immunuphenotypic
      examinations of peripheral blood and bone marrow specimens. Total PAI activity
      was measured with Dade Behring Bericrom PAI reagent in BCS system. Total PAI
      activity was higher than 3.5 U/ml in 11 AML patients while it was normal (0.3-3.5
      U/ml) in control group (P < 0.01). There was no significant difference in total
      PAI activity between AML subgroups (P > 0.05). We found significant difference in
      total PAI activity between patients who have active disease and remission. In
      conclusion, the total PAI activity could be accepted as a relapse and an initial
      diagnosis criterion of AML patients during follow up.

PMID- 16999722
TI  - Littoral-cell angioma as a rare cause of splenomegaly.
AB  - We report the case of a littoral-cell angioma of the spleen, a recently described
      benign vascular tumour, whose imaging and pathological characteristics have been
      discussed only by a few authors. The diagnosis was made after elective
      splenectomy. The CT images, scintigraphy and histological specimens are
      presented, and differential diagnoses discussed.

PMID- 16999723
TI  - Inhaled nitrous oxide (Entonox) as a short acting sedative during bone marrow
      examination.
AB  - Bone marrow aspiration and biopsy is a procedure of central importance in the
      diagnosis of haematological disease and is one that can be safely performed in
      the outpatient clinic using only local anaesthesia. We evaluated the role of
      inhaled nitrous oxide (Entonox) as an adjuvant to local anaesthesia (LA) in
      patients requiring bone examination. We prospectively studied the role of Entonox
      in patients attending our outpatient department who required bone marrow
      examination. All patients received LA with injected 2% lignocaine but patients
      were then assigned to either LA alone or LA plus inhaled Entonox. Following the
      procedure patients were given a questionnaire and asked to score the discomfort
      associated with the procedure. Twenty-eight of 85 patients (33%) who received LA
      alone scored their pain as 3 (severe) compared with seven of 51 patients (14%)
      who received LA plus Entonox, P = 0.013. No adverse events were associated with
      Entonox use. Forty-three of the 51 patients who received Entonox stated that they
      would prefer to use this method of anaesthesia again. We conclude that inhaled
      Entonox is a useful adjuvant to local anaesthesia for patients undergoing bone
      marrow examination.

PMID- 16999724
TI  - Simplified sensitive method for the detection of B-cell clonality in lymphoid
      malignancies.
AB  - Molecular response and monitoring of minimal residual disease (MRD) is becoming
      an essential part of most protocols for treating leukemia and lymphoma patients.
      Detection of abnormal clones by PCR analysis of complementarity determining
      regions (CDRs) in immunoglobulin genes is currently standard practice for
      diagnosis, but is not widely used to monitor MRD because of the low sensitivity
      of assays that use consensus primers. Use of specific primers can improve the
      sensitivity of the assay, but is a cumbersome, expensive, and time-consuming
      process. We developed a simple and cost-effective approach to detect MRD in B
      cell malignancies that is usable in clinical laboratories. The new assay uses
      ligase chain reaction (LCR) to detect clonality. The sensitivity of the LCR assay
      is 1 per 500,000 cells, and it can detect all subclones that were present in the
      pretherapy diagnostic sample.

PMID- 16999725
TI  - Venous stasis and routine hematologic testing.
AB  - Prolonged venous stasis, as generated by a long tourniquet placement, produces
      spurious variations in several measurable analytes. To verify to what extent
      venous stasis influences routine hematologic testing, we assessed routine
      hematologic parameters, including hemoglobin, hematocrit, red blood cell count
      (RBC), main cell hemoglobin (MHC), main cell volume (MCV), platelet count (PLT),
      main platelet volume (MPV), white blood cell count (WBC) and WBC differential on
      the Advia 120 automated hematology analyzer in 30 healthy volunteers, either
      without venous stasis (no stasis) or after application of a 60 mmHg standardized
      external pressure by a sphygmomanometer, for 1 (1-min stasis) and 3 min (3-min
      stasis). Although the overall correlation between measures was globally
      acceptable, the mean values for paired samples were significantly different in
      all parameters tested, except MCV, MHC, PLT, MPV, eosinophils, basophils and
      large unstained cells after 1-min stasis and all parameters except MCV, MHC, MPV
      and basophils after 3-min venous stasis. As expected RBC, hemoglobin and
      hematocrit displayed a significant trend towards increase, whereas WBC and the
      WBC subpopulations were decreased. Difference between measurements by Bland and
      Altman plots exceeded the current analytical quality specifications for desirable
      bias for WBC, RBC, hemoglobin, hematocrit, lymphocytes and monocytes in samples
      collected after either 1- and 3-min stasis. These results provide clear evidence
      that venous stasis during venipuncture might produce spurious and clinically
      meaningful biases in the measurement of several hematologic parameters, prompting
      further considerations on the usefulness of adopting appropriate preventive
      measures for minimizing such influences.

PMID- 16999726
TI  - Unusual presentation of large B cell lymphoma: a case report and review of
      literature.
AB  - Diffuse large B cell lymphoma (DLBCL) is the largest subtype of non-Hodgkin's
      lymphomas (NHLs) and is characterized by relatively frequent extranodal
      presentation. In these cases, the most common extranodal localizations are
      stomach, CNS, bone, testis and liver. Simultaneous detection of multiple
      extranodal involvement at presentation is quite uncommon, with the majority of
      these cases characterized by gastric or intestinal disease localization.
      Retrospective analysis concerning multifocal extranodal NHLs never pointed out
      disease features such as those described here. We report a patient with an
      unusual presentation of DLBCL, characterized by adrenal and renal involvement,
      associated with symptoms and signs of the cold agglutinin disease and a
      hypercoagulable state. Subsequently, computed tomography (CT) and
      fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning disclosed a
      rapidly extensive spread to nodes and bones. Cytofluorimetric analysis of a renal
      specimen showed medium-to-large lympho-monocytoid elements positive for CD20 with
      monoclonal expression of immunoglobulin kappa light chain. Histopathological
      examination confirmed a renal CD20 positive DLBCL localization.

PMID- 16999727
TI  - A case representing coexistence of acute myeloblastic leukemia and
      dedifferentiated liposarcoma: the possible role of chemotherapy in triggering
      dedifferentiation.
AB  - Acute myelogenous leukemia (AML) is a hematological disorder that is
      characterized by an abnormal proliferation of immature myeloid cells.
      Dedifferentiated and well-differentiated liposarcomas are the two pathological
      subtypes of liposarcoma, based on the WHO classification. Transition from well
      differentiated to dedifferentiated liposarcoma is a well-recognized phenomenon.
      Well-differentiated tumors are known to have low malignancy grade. However, when
      dedifferentiation occurs, the tumor acquires the aggressive features of a fully
      malignant lesion. This process largely is believed to progress in a time
      dependant manner; however, time is not the only factor of importance. The
      potential roles of other factors in this transition are still unclear. To date,
      the coexistence of AML and liposarcoma has not been reported in the literature.
      In this paper, we report on a case of coexistence of AML and liposarcoma, and on
      the unusual behavior of a well-differentiated tumor after dedifferentiation
      occurs.

PMID- 16999728
TI  - Persistent pure red cell aplasia due to parvovirus B19 infection in a patient
      with Turner's syndrome.

PMID- 16999729
TI  - Abnormal expansion of naive B lymphocytes after unrelated cord blood
      transplantation--a case report.
AB  - A 33-year-old woman underwent unrelated cord blood transplantation (U-CBT) for
      myelodysplastic syndrome (MDS)-related secondary AML. She showed impressive
      increases in the number of CD19+ B cells in bone marrow and CD19+27-IgD+ B cells
      in peripheral blood from about 1 month to 3 months after U-CBT. The serum level
      of IL-6 temporarily increased after transplantation, and this increase seemed to
      be correlated with the expansion of CD19+ B cells. Although, compared with BMT,
      little is known about the kinetics of hematological and immunological
      reconstitution in U-CBT, there was initial B-cell recovery after CBT as some
      described. This B cell recovery may be associated with a high number of B-cell
      precursors present in cord blood (CB). The phenomenon of naive B lymphocyte
      expansion that we found might be associated with a high number of B-cell
      precursors present in CB.

PMID- 16999730
TI  - Delayed diagnosis of congenital factor IX deficiency (Christmas disease) in a
      girl with Turner's Syndrome.
AB  - Patients with Turner's syndrome are at risk of X-linked recessive disorders. We
      report a case of a young girl with Turner's syndrome with persistent mildly
      abnormal coagulation studies associated with a mild to moderate bleeding
      diathesis. The abnormalities were initially attributed to intrahepatic
      cholestasis and were partially responsive to vitamin K. After an interval of
      several years an episode of unexplained iron deficiency anaemia prompted re
      investigation of the mild coagulopathy. Disproportionate reduction in the factor
      IX concentration and restoration of haemostasis with factor IX concentrate lead
      to a revised provisional diagnosis of mild haemophilia B which was subsequently
      confirmed by sequencing the factor IX gene.

PMID- 16999731
TI  - Dual diagnoses of hereditary hyperferritinaemia-cataract syndrome and hereditary
      haemochromatosis.
AB  - A 30-year-old woman was found to have hyperferritinaemia after presenting with
      menorrhagia and lethargy. Serum iron studies did not confirm iron overload.
      Further investigations revealed two distinct genetic mutations of iron
      haemostasis--homozygosity for C282Y mutation of the HFE gene on chromosome 6 and
      heterozygosity for A40G mutation in the iron response element of ferritin light
      chain on chromosome 19. These mutations are responsible for the diseases
      hereditary haemochromatosis (autosomal recessive) and hereditary
      hyperferritinaemia-cataract syndrome (autosomal dominant) respectively. This is
      the first description of such a patient.

PMID- 16999732
TI  - Helicobacter pylori and cobalamin deficiency.

PMID- 16999734
TI  - Chromatin immunoprecipitation-mediated target identification proved aquaporin 5
      is regulated directly by estrogen in the uterus.
AB  - Estrogens play a central role in the reproduction of vertebrates and affect a
      variety of biological processes. The major target molecules of estrogens are
      nuclear estrogen receptors (ERs), which have been studied extensively at the
      molecular level. In contrast, our knowledge of the genes that are regulated
      directly by ERs remains limited, especially at the level of the whole organism
      rather than cultured cells. In order to identify genes that are regulated
      directly by ERs in vivo, we used estrogen treated mouse uterus and performed
      chromatin immunoprecipitation. Sequence analysis of a precipitated DNA fragment
      enabled alignment with the mouse genomic sequence and revealed that the promoter
      region of the gene encoding aquaporin 5 (AQP5) was precipitated with antibody
      against ER alpha. Quantitative PCR and DNA microarray analyses confirmed that
      AQP5 is activated soon after administration of estrogen. In addition, the
      promoter region of AQP5 contained a functional estrogen response element that was
      activated directly by estrogen. Although several AQP genes are expressed in the
      uterus, only direct activation of AQP5 could be detected following treatment with
      estrogen. This chromatin immunoprecipitation-mediated target identification may
      be applicable to the study of other transcription factor networks.

PMID- 16999735
TI  - Role of the cholinergic system in regulating survival of newborn neurons in the
      adult mouse dentate gyrus and olfactory bulb.
AB  - Neurogenesis in the subgranular zone of the hippocampal dentate gyrus and
      olfactory bulbs continues into adulthood and has been implicated in the cognitive
      function of the adult brain. The basal forebrain cholinergic system has been
      suggested to play a role in regulating neurogenesis as well as learning and
      memory in these regions. Herein, we report that highly polysialylated neural cell
      adhesion molecule (PSA-NCAM)-positive immature cells as well as neuronal nuclei
      (NeuN)-positive mature neurons in the dentate gyrus and olfactory bulb express
      multiple acetylcholine receptor subunits and make contact with cholinergic
      fibers. To examine the function of acetylcholine in neurogenesis, we used
      donepezil (Aricept), a potent and selective acetylcholinesterase inhibitor that
      improves cognitive impairment in Alzheimer's disease. Intraperitoneal
      administrations of donepezil significantly enhanced the survival of newborn
      neurons, but not proliferation of neural progenitor cells in the subgranular zone
      or the subventricular zone of normal mice. Moreover, donepezil treatment reversed
      the chronic stress-induced decrease in neurogenesis. Taken together, these
      results suggest that activation of the cholinergic system promotes survival of
      newborn neurons in the adult dentate gyrus and olfactory bulb under both normal
      and stressed conditions.

PMID- 16999736
TI  - The testes-specific bZip type transcription factor Tisp40 plays a role in ER
      stress responses and chromatin packaging during spermiogenesis.
AB  - We previously reported that the spermatid-specific transcription factor Tisp40
      functions through UPRE and CRE. To investigate Tisp40 function in vivo, we
      generated TISP40(-/-) mice. TISP40(-/-) mice were born at expected ratios, were
      healthy, and mutant males bred normally. However, the ER stress-response protein
      Grp78/BiP accumulated in the TISP40(-/-) testis and RAMP4 (Ribosome-associated
      membrane protein 4) mRNA level was up-regulated. Disruption of TISP40 caused ER
      stress and activation of caspase 12 but not caspase 9, leading to apoptosis of
      meiotic/postmeiotic germ cells. On the other hand, DAPI staining and electron
      microscopy revealed that epididymal sperm nuclei were abnormally relaxed in the
      TISP40(-/-) testis, a phenotype that was independent of the expression and
      maturation of transition proteins and protamines but due to abnormally retained
      histones. Histones localized to the cytoplasm as well as to the nucleus and were
      also retained in epididymal sperm. Histones H2A and H4 were dramatically up
      regulated and the acetylation of H2A, H2B and H4 was also enhanced in the TISP40(
      /-) testis. Taken together, we conclude that Tisp40 plays an important role in
      the unfolded protein response of the testis and in regulating the maturation of
      sperm head nuclei.

PMID- 16999737
TI  - New reporter system for Per1 and Bmal1 expressions revealed self-sustained
      circadian rhythms in peripheral tissues.
AB  - A new reporter system for monitoring expressions of two clock genes, Per1 and
      Bmal1, from a single tissue in culture was developed in mice. Reporters are
      Vargula hilgendorfii luciferase (VL) and firefly luciferase (FL), whose
      activities are increased in parallel with Per1 and Bmal1 expressions,
      respectively. Formal properties of the circadian system in transgenic mice are
      indistinguishable from those in wild-type animals. Circadian rhythms in Per1-VL
      and Bmal1-FL in the suprachiasmatic nucleus (SCN) were robust and anti-phasic,
      although they were phase delayed by 4-8 h as compared with circadian rhythms in
      respective transcript levels in vivo. In peripheral tissues such as liver,
      circadian rhythms in Bmal1-FL persisted for more than 3 weeks. In the course of
      prolonged culture, circadian rhythms apparently damped out, but were restored
      immediately by refreshment of the culture medium. Restoration of the circadian
      rhythm is unlikely to be due to resetting of desynchronized population
      oscillation, because peripheral circadian rhythms did not show a type 0 phase
      response curve (PRC) for medium refreshment, a requirement for instantaneous
      resetting of circadian oscillation. Long-term persistence of circadian
      oscillation in spite of external perturbations supports an idea that circadian
      oscillations in peripheral tissues are self-sustained.

PMID- 16999738
TI  - Ammonium transporter genes in the fission yeast Schizosaccharomyces pombe: role
      in ammonium uptake and a morphological transition.
AB  - Ammonium is an important source of nitrogen for many microorganisms, including
      yeast, and its availability also has substantial effects on the nitrogen
      metabolism and development of yeast cells. Three ammonium transporter genes of
      the fission yeast Schizosaccharomyces pombe, named amt1, amt2, and amt3, were
      identified on the basis of amino acid sequence similarity to members of the
      ammonium transporter/methylammonium permease (Amt/Mep) family. A series of
      strains were constructed that carry all combinations of amt deletion (amt delta)
      mutations, and tested for growth on low ammonium and resistance to the toxic
      ammonium analog methylammonium. The amt1 delta and amt2 delta single mutants had
      different growth defects, and the amt1 delta amt2 delta double mutant displayed a
      much more severe growth defect on < or = 5 mM ammonium. All single mutants
      exhibited methylammonium resistance but to different extents: amt2 delta was the
      most resistant and amt3 delta was the least. These results suggest that the amt
      genes encode functional transporters with distinct uptake properties. In response
      to ammonium limitation, the wild-type strain isogenic to the amt delta mutants
      underwent filamentous growth underneath the surface of solid medium. No such
      filamentous invasive growth, however, was observed for the amt1 delta mutant,
      indicating that Amt1 transporter is required for ammonium limitation-induced
      filamentous invasive growth.

PMID- 16999739
TI  - Interaction of SPIN90 with syndapin is implicated in clathrin-mediated endocytic
      pathway in fibroblasts.
AB  - SPIN90, a 90-kDa Nck-interacting protein with a SH3 domain, plays a role in
      sarcomere formation and myofibril assembly, and its phosphorylation is modulated
      by cell adhesion and Erk activation. Here we demonstrate that SPIN90 participates
      in receptor-mediated endocytic pathway in fibroblasts. We identified syndapin
      (synaptic dynamin-binding protein) as a SPIN90 interacting protein using yeast
      two-hybrid screening. SPIN90 directly binds the SH3 domain of syndapin via its
      proline rich domain in vitro and in vivo and also associates with clathrin. Over
      expression of SPIN90-full length in COS-7 cells inhibited transferrin uptake, a
      marker of endocytosis. Interestingly, SPIN90-PRD, a syndapin-binding domain,
      significantly inhibited endocytosis, and the inhibition was reversed by co
      expression of syndapin. Depleting SPIN90 through antibody microinjection or
      Knocking it down using siRNAs also significantly inhibited transferrin
      internalization. Moreover, early endosomal marker proteins (EEA1 and Rab5)
      appeared to closely associate or partially co-localize with SPIN90 in endosomes
      and an internalized FITC-dextran and Texas Red-EGF were found on the endosomes in
      association with SPIN90. Time-lapse video showed that GFP-SPIN90 travels with
      moving vesicles within living cells. Taken together, these findings suggest that
      SPIN90 is implicated in receptor-mediated endocytic pathway in fibroblasts.

PMID- 16999740
TI  - Sustained cell proliferation of renal epithelial cells in mice with inv mutation.
AB  - A tubule system is an important component of the nephron, which is the structural
      and functional unit of the kidney. Expansion of renal tubules results in renal
      cysts. Hereditary forms of renal cystic diseases suggest that tubular size is
      determined genetically. The inv was discovered as a mutant with renal cysts and
      situs inversus. Inv/inv, inv deltaC::GFP (inv deltaC) mouse was created by the
      introduction of the inv gene lacking the C-terminus (inv deltaC) into inv/inv
      mice. The mouse develops multiple renal cysts without situs abnormality, giving
      us an opportunity to study inv function in renal tubular structure maintenance.
      In the present study, we showed that inv suppresses cyst progression in a dose
      dependent manner and that the inv deltaC cystic kidneys showed increased cell
      proliferation and apoptosis. Cell cycle regulators for G1-S progression were
      activated in the cystic kidney. Furthermore, cDNA microarray and semiquantitative
      RT-PCR analysis showed that growth-related genes maintained a high level of
      expression in the cystic kidney at 4 weeks of age whereas they were decreased in
      control kidneys, suggesting that cells in inv deltaC kidney are still active in
      the cell cycle. One of the inv protein functions may provide a stop signal for
      renal epithelial cell proliferation.

PMID- 16999741
TI  - Dnmt3a2 targets endogenous Dnmt3L to ES cell chromatin and induces regional DNA
      methylation.
AB  - DNA methylation is involved in fundamental cellular processes such as silencing
      of genes and transposable elements, but the underlying mechanism of regulation of
      DNA methylation is largely unknown. DNA methyltransferase 3-like protein
      (Dnmt3L), a member of the Dnmt3 family of proteins, is required during the
      establishment of DNA methylation patterns in germ cells. Dnmt3L does not possess
      enzymatic activity. Rather, in vitro analysis indicates that Dnmt3L stimulates
      DNA methylation by both Dnmt3a and Dnmt3b through direct binding to these
      proteins. In the current study, we demonstrated that in vivo, Dnmt3L physically
      and functionally interacted with the Dnmt3 isoform Dnmt3a2. In wild-type
      embryonic stem (ES) cells, but not in cells lacking Dnmt3a, endogenous Dnmt3L was
      concentrated in chromatin foci. In ES cells deficient in both Dnmt3a and Dnmt3b,
      Dnmt3L was distributed diffusely throughout the nucleus and cytoplasm, and
      ectopic expression of Dnmt3a2, but not Dnmt3a or Dnmt3b, restored wild-type
      Dnmt3L localization. We showed that endogenous Dnmt3L physically interacted with
      Dnmt3a2, but not Dnmt3a or Dnmt3b, in ES cells and embryonic testes. We also
      found that specific CpG sites were demethylated upon depletion of either Dnmt3a
      or Dnmt3L, but not Dnmt3b, in ES cells. These results provide evidence for a
      physical and functional interaction between Dnmt3L and Dnmt3a2 in the nucleus. We
      propose that Dnmt3a2 recruits Dnmt3L to chromatin, and induces regional DNA
      methylation in germ cells.

PMID- 16999742
TI  - Guidelines for assigning authorship.

PMID- 16999743
TI  - Stimulant medications: a trade-off? The lived experience of adolescents with
      ADHD.
AB  - PURPOSE: The purpose of this study was to gain information and insight about
      prescription stimulant medication use among children and adolescents with
      attention deficit-hyperactivity disorder (ADHD) across developmental stages.
      DESIGN AND METHODS: Investigators conducted semistructured qualitative interviews
      with 15 college students with ADHD. Follow-up interviews confirmed and validated
      information obtained during initial interviews. RESULTS: Qualitative data
      analysis resulted in three global categories related to the use of prescription
      stimulant medication from childhood to late adolescence: (a) the early years, (b)
      "the trade-off," and (c) stimulant medications in college. PRACTICE IMPLICATIONS:
      Increased education about prescription stimulant medications and closer
      management is needed to reduce side effects and minimize the risks of misuse.

PMID- 16999744
TI  - Assessing emergency preparedness of families caring for young children with
      diabetes and other chronic illnesses.
AB  - PURPOSE: To help children with chronic illnesses and their caregivers assess
      emergency preparedness. CONCLUSIONS: Little work has been done to ascertain
      patient adherence levels to these recommendations. Additionally, little is known
      about the seeking patterns of healthcare providers and/or changes in
      interventions based on certain elements of emergency preparedness, such as the
      presence of medical alert identification and an emergency kit. PRACTICE
      IMPLICATIONS: Healthcare providers must discover their patients' level of
      emergency preparedness and facilitate the acquisition and implementation of
      elements of emergency preparedness that meet their patients' needs.

PMID- 16999745
TI  - Pouring rights contracts and childhood overweight: a critical theory perspective.
AB  - PURPOSE: To examine school environments, and in particular, pouring rights
      contracts and how they relate to childhood overweight from a critical theory
      perspective. CONCLUSIONS: Pouring rights contracts provide a profit to powerful
      mega-corporations at the expense of children's health. There is a need to move
      beyond a solely individual approach to addressing childhood overweight and
      involve a social ecology approach. This would involve a push for social change,
      including removal of soda machines from schools, and changing marketing practices
      targeted at children. PRACTICE IMPLICATIONS: Nurses are poised in community
      situations to actively effect social changes to improve health outcomes of our
      nation's most vulnerable people, but nurses must get involved.

PMID- 16999746
TI  - Recruitment and retention of Latino adolescents to a research study: lessons
      learned from a randomized clinical trial.
AB  - PURPOSE: To describe facilitators and barriers to participation and retention of
      Latino adolescents in a randomized clinical trial. DESIGN AND METHODS:
      Participants were part of a randomized clinical trial designed to reduce HIV
      sexual risk behavior among Latino youth. Responses from 106 randomly selected
      respondents from the 3-month follow-up were content analyzed. RESULTS: Four main
      facilitator patterns emerged: peer/family support, program incentives,
      commitment, and desire to help. Participation barriers included conflicts with
      other commitments, embarrassment, and lack of peer support. PRACTICE
      IMPLICATIONS: Recruitment and retention of Latino adolescents in research studies
      is critical to building a research base for nursing practice.

PMID- 16999747
TI  - Changes in CPR and ECC for pediatric nurses.

PMID- 16999748
TI  - A multidisciplinary approach to vascular access in children.

PMID- 16999749
TI  - What a difference a point makes! Scaling issues.

PMID- 16999750
TI  - Transitioning families to adult cystic fibrosis care.

PMID- 16999751
TI  - Immigration: changing needs and responses.

PMID- 16999752
TI  - A review of nearly two decades in an autologous blood programme: The rise and
      fall of activity.
AB  - Autologous blood donation (ABD) has been widely recommended. Data from one of the
      oldest hospital-based programmes in Canada describe both activities and
      drawbacks. Data were compared over the nearly two decades of activity that peaked
      in 1996. A 5-year review of recent activity showed that of the 2410 patients
      referred for consideration, 1823 (75.64%) were accepted into the programme.
      Surgical services requested 5825 units of autologous blood. Of these, 3147 units
      were donated by 1536 patients, 803 units were transfused in the operating room
      and 558 units were given postoperatively. In total, only 1361 units (43.25%) were
      transfused. The mean age of the patients was 58 years (median 61 years and mode
      69 years). The haemoglobin concentrations before donation were significantly
      higher, averaging 145.2 g L(-1) before donation and 114.9 g L(-1) immediately
      before surgery, whereas at the time of discharge, the haemoglobin concentration
      averaged 126.2 g L(-1) (P = 0.0001) in transfused patients. Data from this well
      established ABD programme indicate less than 50% overall utilization. The
      activity in the programme increased until 1996 following which it dropped
      progressively. The low haemoglobin concentration after surgery is of concern and
      should foster a transfusion algorithm for these patients.

PMID- 16999753
TI  - Autologous blood donation and subsequent blood use in patients undergoing total
      knee arthroplasty.
AB  - Autologous blood donation is designed to avoid complications from allogeneic
      blood, leaving units of blood in the general blood supply. It is unclear how
      efficient these programmes are in accomplishing these goals. It is unclear if
      autologous donation provokes increased need for any transfusion following surgery
      and whether it can be avoided in low-risk surgeries. Of 430 patients undergoing
      unilateral primary knee replacement arthroplasty over 12 months in our hospital,
      309 had autologous donations and 121 did not. Of the 121 patients who did not
      donate, 36% completed surgery without transfusion, whereas only 17% of those who
      had autologous donations did so (P < 0.05). Age less than 65 years, higher
      baseline and postoperative haemoglobin levels were associated with lower
      transfusion rates. Patients who had autologous donations were approximately four
      times more likely to be transfused. As the number of autologous units donated
      increased, transfusions following surgery increased. Autologous donation did
      reduce allogeneic blood transfusions. Therefore, autologous blood donation for
      unilateral total knee arthroplasty is associated with overall increased
      transfusion rates, but with reduced need for allogeneic blood, independent of
      other clinical factors associated with transfusion. Therefore, there is need for
      reconsideration of these programmes relative to specific surgeries.

PMID- 16999754
TI  - Efficacy, safety and user-friendliness of two devices for postoperative
      autologous shed red blood cell re-infusion in elective orthopaedic surgery
      patients: A randomized pilot study.
AB  - To determine the safety, efficacy and user-friendliness of two different
      postoperative autologous blood re-infusion systems, an open, randomized,
      controlled study was performed. Eligible consecutive primary and revision total
      hip and knee replacement patients were randomized for one of the two systems or
      for a control group in which shed blood was not re-infused. The nursing staff
      scored user-friendliness. Patients were monitored after re-infusion. In all three
      patient groups, a restrictive transfusion trigger was used. Sixty-nine of 70
      randomized patients were evaluated. Ease of use, efficacy and safety of both re
      infusion systems were comparable. There was no difference in allogeneic blood use
      between the groups. Thirty per cent of the patients re-infused with autologous
      blood developed a mainly mild, febrile transfusion reaction. No other adverse
      reactions were seen. Signs of coagulopathy after re-infusion were not found. In
      multivariate analysis, autologous re-infusion was an independent factor
      associated with a shorter hospital stay. Both postoperative autologous blood re
      infusion systems were of equal efficacy and safety. The contribution of
      autologous wound blood re-infusion to reduce allogeneic transfusions must be
      investigated in a larger study.

PMID- 16999755
TI  - Significant reduction in blood loss in patients undergoing minimal extracorporeal
      circulation.
AB  - Several recent studies have shown differences in blood loss and allogeneic
      transfusion requirements between on-pump and off-pump coronary artery bypass
      grafting (CABG). Recently a new concept, the mini-extracorporeal circulation, was
      introduced to minimize the side effects of extracorporeal circulation. Therefore,
      there are no data comparing the three techniques with special emphasis to blood
      loss and transfusion requirements. Two hundred and eighty-five patients
      undergoing first-time coronary artery bypass grafting were retrospectively
      matched for number of grafts, age and sex. Ninety-five patients underwent surgery
      with the off-pump CABG (OPCAB) technique, 97 patients using conventional CABG
      with cold cardioplegia (CCABG) and 93 patients with the mini-extracorporeal
      circuit with warm blood cardioplegia (MCABG). Blood loss for the CCABG group with
      a mean loss of 819 +/- 557 mL and the OPCAB group with a mean loss of 870 +/- 768
      mL was significant different compared to the MCABG group with a mean loss of 679
      +/- 290 mL. The use of units red blood cell units was significantly higher for
      CCABG group and OPCAB group compared to the MCABG group. On the day of operation
      the use of platelet concentrate was significantly higher for the CCABG group
      compared to MCABG group. As a consequence of improvements of several components
      of the mini heart lung machine, significantly less blood products are needed in
      MCABG patients. The expected reduced need for transfusion when the pump was
      completely avoided could not be confirmed in this single retrospective cohort
      study.

PMID- 16999756
TI  - Perioperative intravenous iron preserves iron stores and may hasten the recovery
      from post-operative anaemia after knee replacement surgery.
AB  - In unilateral total knee replacement (TKR), perioperative blood loss, low
      transfusion thresholds and short hospital stay result in patients being
      discharged with low haemoglobin (Hb). We assessed the effects of perioperative
      administration of intravenous iron, with or without erythropoietin, plus a
      restrictive transfusion threshold (Hb < 80 g L(-1)) both on transfusion rate and
      recovery from post-operative anaemia. TRK patients received iron sucrose (2 x 200
      mg per 48 h, iv) (Group IVI, n = 129). Patients with admission Hb < 130 g L(-1),
      also received erythropoietin (1 x 40 000 IU, sc) (Group EPO, n = 19).
      Perioperative clinical and laboratory data were obtained. Mean Hb loss was 36 g
      L(-1), but only seven patients were transfused (5%). Pre-operatively, 66 (45%)
      patients did not have enough stored iron to compensate Hb loss. At post-operative
      day 30, only 15% were anaemic, 70% of Hb loss and 92% of pre-operative Hb were
      recovered and ferritin increased by 73 microg L(-1) (P < 0.01), although
      erythropoietic response was higher in patients receiving erythropoietin (P <
      0.05). No adverse effects of iron sucrose or erythropoietin were witnessed. This
      protocol seems to reduce allogeneic blood transfusion rate and may hasten the
      recovery from post-operative anaemia in TKR patients, without depleting iron
      stores. Further studies are needed to ascertain which patients may benefit of
      extended intravenous iron and/or erythropoietin administration.

PMID- 16999757
TI  - Transfusion-related acute lung injury in the paediatric patient: Two case reports
      and a review of the literature.
AB  - Transfusion-related acute lung injury (TRALI) is increasingly recognized as a
      major complication of transfusion therapy; it was the leading cause of
      transfusion-related fatalities in the United States in 2003. Most cases of TRALI
      that have been reported are in adult patients. We present two cases of TRALI that
      occurred in children and review the existing literature of paediatric TRALI. The
      paediatric TRALI case reports highlight two laboratory findings that can help in
      the diagnosis of TRALI: transient leucopenia and an elevated pulmonary oedema
      fluid/plasma protein ratio. These two simple diagnostic tests can help rule out
      other diagnoses and add confidence to the clinical diagnosis of TRALI. Finally,
      our first case also highlights the potential danger of directed maternal blood
      donations, which may increase the risk of paediatric TRALI.

PMID- 16999758
TI  - Diagnosis of acute foetal distress does not preclude banking of umbilical cord
      blood units.
AB  - Clinical diagnosis of acute foetal distress (AFD) is based on several parameters
      such as abnormal foetal heart rate (FHR) pattern and/or meconium liquid staining
      (MLS). Standards for cord blood (CB) banking indicate that AFD should be
      considered as exclusion criteria for CB collection, but precise guidelines on how
      to proceed with CB collection in the presence of AFD signs during labour are not
      available. We evaluated whether the presence of FHR abnormality and/or MLS during
      labour 1) reduced the CB collection activity; 2) were associated with the
      infant's acidaemia or asphyxia and 3) deteriorated the biological characteristics
      of CB units. Thirty-three units of CB were evaluated for biological parameters,
      gas values and newborn's Apgar score. The results were compared with a control
      group of 33 consecutive units previously banked. No differences were observed
      between the two groups and all but one newborn showed normal Apgar score and
      absence of metabolic acidaemia. The results showed that 1) AFD reduced the CB
      collection activity by 10% each year; 2) the majority of CB units collected in
      the presence of abnormal FHR and/or meconium have biological characteristics
      eligible for banking; 3) FHR alterations or meconium in the presence of normal
      gas analysis do not represent certain diagnosis of AFD.

PMID- 16999759
TI  - FACS technology used in a new rapid bacterial detection method.
AB  - Culture methods for bacterial detection (BacT/ALERT or Pall eBDS) are currently
      implemented in blood donor screening procedures in many countries. Experience in
      the first years after implementation of these detection assays showed that
      although the analytical sensitivity was extremely high (about 1 CFU mL(-1)), the
      majority of these platelets were still transfused before a positive screening
      result was attained. Rapid technologies were developed to more effectively
      prevent transfusion-transmitted bacterial infection. In this study, a new rapid
      bacterial detection method based on fluorescence-activated cell sorting (FACS)
      technology was developed. Bacteria were stained with thiazole orange dye for 5
      min and measurement was taken immediately after staining. The entire process took
      only 30 min. Six transfusion-relevant bacteria strains were tested in a spiking
      study. Without pre-incubation in a special bacteria growth medium, analytical
      sensitivity ranged between 10(5) CFU mL(-1) (Klebsiella oxytoca and Serratia
      marcesens) and 10(3) CFU mL(-1) (Escherichia coli). Sensitivity could be improved
      to 10(1) CFU mL(-1) for all tested bacteria by adding a pre-incubation step (6 h
      at 37 degrees C). Although preliminary in nature, results of our study suggest
      that bacterial detection by FACS technology in conjunction with a pre-incubation
      step offers a sensitive alternative technology to culture methods. Additionally,
      it provides the benefit of a rapid test time and the opportunity of preventing
      bacterial transmitted infections more effectively.

PMID- 16999760
TI  - Differences in platelet growth factor release and leucocyte kinetics during
      autologous platelet gel formation.
AB  - Three commercial systems for whole blood separation were compared to obtain the
      buffy coat composed of platelet-rich plasma (BC-PRP) and leucocytes . These
      samples of the buffy coat were used to make a platelet gel (PG), which was used
      to measure platelet growth factor (PGF) release, to perform a white blood cell
      (WBC) count and to measure myeloperoxidase (MPO) release from WBCs. Aliquots of
      whole blood obtained from ten volunteers were distributed either to a blood cell
      separator (The Electa Cell-Separator, E-CS) or to a tabletop centrifuge
      (Gravitational Platelet Sequestration System, GPS) to prepare the BC-PRP. The
      third system combines the BC-PRP production by E-CS with a micro porous filter
      (Autologous Growth Factor filter, AGF) to enrich for the BC-PRP. Autologous
      thrombin was used to activate the BC-PRP and to prepare the PG and subsequently
      to degranulate the platelet concentrate. Platelet-derived growth factor-AB and
      transforming growth factor-beta1 were present in high levels after thrombin
      activation of the E-CS or GPS prepared samples. However, the AGF prepared samples
      released their growth factors before thrombin activation. The WBCs were
      significantly increased with each of the three systems. Contrary to the AGF, no
      leucocyte degranulation occurred with the E-CS or GPS prepared samples, based
      upon the low MPO concentrations in the BC-PRP. The three types of apparatus had
      different harvesting capacities for collecting the enriched platelets and the
      release of high concentrations of PGF. When the E-CS and GPS, but not the AGF,
      were used, low levels of MPO were maintained in the PG, which potentially
      contributes to antimicrobial properties of platelet gel at the site of
      application.

PMID- 16999761
TI  - Establishment of an HPA-1- to -16-typed platelet donor registry in China.
AB  - In order to determine gene frequencies of human platelet antigen (HPA) and
      establish a panel of accredited HPA-1a, -2a, -4a, -5a and -6a-negative donors as
      well as an HPA-typed platelet donor registry, a total of 1000 Chinese donors of
      Han nationality (500 from north China and 500 from south China) were typed for
      HPA-1 through -16 using a DNA-based polymerase chain reaction with sequence
      specific primers genotyping method. The gene frequencies of HPA-1b, -2b, -3b, 
      4b, -5b, -6bw, -10bw and -15b were 0.0060, 0.0485, 0.4055, 0.0045, 0.0140,
      0.0135, 0.0005 and 0.4680, respectively. The HPA-7bw, -8bw, -9bw, -11bw, -12bw, 
      13bw, -14bw and -16bw alleles were not found. The HPA-2b and -5b homozygous
      donors were detected at low frequencies. The HPA mismatch probabilities
      potentially leading to alloimmunization in random platelet transfusion vary with
      a region from 0.1% to 37% depending on the distribution patterns of common and
      less common alleles in each system. This study provides a useful HPA-typed
      plateletpheresis donor registry in China and could improve platelet antibody
      detection and HPA-matched platelet transfusion in alloimmune thrombocytopenic
      patients.

PMID- 16999762
TI  - Repeat ABO-incompatible platelet transfusions leading to haemolytic transfusion
      reaction.
AB  - A 65-year-old woman, blood group A RhD positive, who had completed her first
      course of induction chemotherapy for acute myeloid leukaemia was transfused with
      apheresis platelets over a number of days. On three occasions she received group
      O RhD positive units, which had been screened and found not to contain high-titre
      anti-A,B isoagglutinins. Following the third unit, she developed a haemolytic
      transfusion reaction and died soon thereafter. This has led to change in policy
      of the supplying centre in testing for high-titre anti-A,B isoagglutinins. Blood
      group O apheresis platelets and fresh-frozen plasma units are now labelled as
      high titre with a cut-off of 1/50 as compared to the previous cut-off of 1/100
      for anti-A,B isoagglutinins. A universal approach to testing donations for high
      titre anti-A,B isoagglutinins, better compliance of guidelines and monitoring of
      patients is necessary.

PMID- 16999763
TI  - The relationship between evidence and practice: some considerations in
      breastfeeding.

PMID- 16999764
TI  - Time to get serious about educating health professionals.

PMID- 16999765
TI  - Assessing learning needs for breastfeeding: setting the scene.
AB  - Breastfeeding has a major contribution to make to public health, yet the UK, like
      many other developed countries, has low rates of breastfeeding. A contributing
      factor is that practitioners are ill-prepared to support breastfeeding women.
      There is a mismatch between the care professionals provide and the support women
      desire. A national breastfeeding learning needs assessment (LNA) was carried out
      in England to provide a comprehensive picture of professional and practitioner
      learning needs and existing training opportunities and resources. The LNA
      comprised five elements, and sought the views of service users through consumer
      organizations and voluntary breastfeeding supporters. Two elements of the LNA are
      reported here. A search of RDLearning, a web-based national resource, provided
      details of existing accredited courses in the UK for practitioners. Ten short
      courses provided by higher education institutions were identified, along with a
      range of courses offered by voluntary and other organizations, such as the
      National Childbirth Trust and UNICEF Baby Friendly Initiative. Second, an e-mail
      survey of 28 key stakeholder organizations was undertaken, with a response rate
      of 68% (n = 18). All but one acknowledged that their members could benefit from
      further breastfeeding knowledge and expertise and were supportive of a national
      breastfeeding education initiative. The most popular forms of education provision
      were workshops and seminars, online and written information. The topic considered
      most important for all practitioners was the health outcomes of breastfeeding.
      Other contributions which stakeholder organizations felt they could make were the
      provision of information resources and setting up specialist interest groups.

PMID- 16999766
TI  - The education of health practitioners supporting breastfeeding women: time for
      critical reflection.
AB  - The protection, promotion and support of breastfeeding has now become a major
      international priority as emphasized in the Global Strategy for Infant and Young
      Child Feeding. Health practitioners, such as midwives, nurses and doctors, have a
      key role to play in providing support to breastfeeding women. This paper provides
      a critical discussion of educational requirements of health practitioners to
      equip them for their supportive role. The effective integration of embodied,
      vicarious, practice-based and theoretical knowledge requires opportunities for
      deep critical reflection. This approach should facilitate personal reflection and
      critical engagement with broader socio-political issues, thus allowing for
      collective understandings and change. Practitioners also need to understand
      breastfeeding as a biopsychosocial process that is dynamic, relational and
      changes over time. Recommendations are outlined with regards to multidisciplinary
      undergraduate education; mentorship schemes with knowledgeable role models
      supporting student practitioners; involvement of voluntary and peer supporters;
      post-registration education; setting of national standards for breastfeeding
      education; tailored education for specific groups; designated funding; and
      involvement of breastfeeding specialists.

PMID- 16999767
TI  - A training needs survey of doctors' breastfeeding support skills in England.
AB  - The study examined the training needs of paediatricians and general practitioners
      (GPs). Respondents rated their competence on 23 breastfeeding support skills,
      importance of update in the next 2 years, actual and potential helpfulness of
      different forms of professional updates, and accessibility in the next 2 years.
      The perception of organizational barriers to breastfeeding support and
      practitioners' knowledge of policies and guidance on breastfeeding were also
      examined. The sample comprised 120 paediatricians and 57 GPs. Response rates were
      estimated as between 4% and 29%, depending upon the method of recruitment.
      Although both groups rated themselves as fairly competent in most of the skill
      areas, they welcomed training in key areas of practice. Paediatricians identified
      more areas for update than GPs (t = 3.44; d.f. = 178; P < 0.00001). Those who
      believed that they were less competent in clinical skills were least likely to
      seek update (r = 0.35; P < 0.00001). Practical forms of training were most often
      welcomed. Only 47% of GPs and 62.5% of paediatricians had access to a local
      breastfeeding policy. There were evident gaps in knowledge on key aspects of
      public health policy, which could influence local practice; for example, 50.8% of
      GPs and 47.5% of paediatricians identified a younger age for introducing solids
      than the minimum according to current government guidance. Organizational
      barriers to breastfeeding support were experienced by all respondents.
      Recommendations include purposively targeting training to those least likely to
      seek training, and developing effective self-study and observational methods of
      learning. All training should be evaluated and implemented alongside
      breastfeeding policies and clinical leadership to improve the practice of all
      healthcare practitioners.

PMID- 16999768
TI  - 'Informal' learning to support breastfeeding: local problems and opportunities.
AB  - This study explored 'informal' learning opportunities in three health economies,
      both for National Health Service (NHS) staff and lay people wishing to promote
      and support breastfeeding and for new mothers wishing to breastfeed. The word
      'informal' indicates local learning opportunities that are not part of recognized
      academic or professional training courses. Semi-structured telephone interviews
      were conducted with 31 key informants, including health visitors, midwives,
      infant feeding advisers, Sure Start personnel, voluntary organization
      representatives, Strategic Health Authority representatives, senior nurses and
      trainers. The results were analysed thematically. In each site, there were
      regular training events for NHS staff to acquire or update knowledge and skills.
      Training was provided by a small number of enthusiasts. Midwives and health
      visitors were the groups who attend most frequently, although many find it
      difficult to make time. Although many training events were multidisciplinary, few
      doctors appeared to attend. Individual staff also used additional learning
      opportunities, e.g. other courses, conferences, web-based learning, and training
      by voluntary organizations. Services offered to lay people by the NHS, Sure Start
      and voluntary organizations included parentcraft, antenatal and post-natal
      classes, breastfeeding support groups, 'baby cafes' and telephone counselling.
      Interviewees' organizations did not have a specific breastfeeding strategy,
      although action groups were trying to take the agenda forward. Local
      opportunities were over-dependent on individual champions working in relative
      isolation, and support is needed from local health economies for the facilitation
      of coordination and networking.

PMID- 16999769
TI  - Addressing the learning deficit in breastfeeding: strategies for change.
AB  - This paper summarizes the findings of the learning needs assessment described in
      this issue. Limitations and strengths are discussed. The paper describes a
      national, multi-sectoral, multidisciplinary picture. Our respondents may over
      represent those with an interest in breastfeeding; if so, the true picture may be
      even more problematic than described here. Major deficits were identified in the
      knowledge and skills of practitioners from all backgrounds and all sectors. Many
      professionals report poor knowledge about breastfeeding and have low levels of
      confidence and clinical competence. Organizational constraints and barriers to
      effective education and practice include fragmentation of care and education,
      lack of facilities, and a low priority being given to breastfeeding. There is a
      range of current educational provision, although not all is fit for purpose.
      Voluntary organizations seem to have higher standards than do some current
      professional learning opportunities. Preferred methods of training include
      practical observation and mentorship, volunteer counsellor involvement in
      training programmes, as well as self-study and online opportunities.
      Recommendations include: a funded, mandatory, interagency and multidisciplinary
      approach; appropriate content; support at local and national levels;
      breastfeeding education to be included in clinical governance and audit
      mechanisms; and further research and evaluation to examine optimum ways of
      providing education and training. Organizational barriers could be addressed
      through a public health policy and evidence-based approach.

PMID- 16999770
TI  - Developing practice in breastfeeding.
AB  - This paper reports on an approach to practice development in breastfeeding as
      part of a national programme of work to address inequalities in maternal and
      child nutrition. The production and dissemination of evidence and guidelines is
      necessary but not sufficient on its own to effect change in practice,
      particularly when dealing with complex public health issues. In the case of
      breastfeeding, review evidence and national guidance have shown that multifaceted
      changes are essential if policy aspirations are to be realized. The objectives of
      the programme described here were to (1) inform and enable practice development
      in breastfeeding in low-income areas; (2) evaluate the impact of approaches used;
      and (3) develop robust approaches and appropriate material for use nationally. A
      conceptual framework was established, and a six-stage process is outlined. The
      recruitment of four sentinel sites across whole health economies, involving
      professionals and the voluntary sector, was an essential component of the
      programme. The strength of the model is that it provides a structured, cross
      sectoral approach to practice development in public health. A key challenge is to
      identify whose responsibility it is to resource practice development when a
      number of disciplines and sectors are involved. This question needs to be
      addressed if public health guidance is to be of sustained benefit.

PMID- 16999772
TI  - Conformational analysis of r207910, a new drug candidate for the treatment of
      tuberculosis, by a combined NMR and molecular modeling approach.
AB  - R207910 is an enantiomeric compound from a new class of antimycobacterial agents,
      the diarylquinolines [Science; 307:223 (2005)]. As enantiospecific interaction is
      required for biologic activity, we have undertaken a combined nuclear magnetic
      resonance and molecular modeling study to gain new insights into its conformation
      in solution and its absolute configuration. A conformational analysis using a
      Monte-Carlo method has been performed on each of the four possible stereomers of
      this compound leading to the identification of their most stable conformation.
      Additional ab initio calculation was performed with emphasis on the strength of
      the observed intramolecular hydrogen bond. Simultaneously, a complete structural
      identification has been carried out by a set of monodimensional and bidimensional
      (1)H-(13)C-NMR experiments. Determination of inter-proton distances has been
      achieved by a series of (1)H-(1)H ROESY NMR experiments with different mixing
      times followed by a volume quantification of the correlations peaks. These
      experimental data were compared with the theoretical distances obtained from the
      conformational analysis. The remarkable match shows that R207910 adopts one of
      the low-energy conformations predicted by molecular modeling and belongs to the
      (RS, SR) couple of diastereoisomers. A posteriori validation of our approach has
      been performed by X-ray structure determination that concluded for the RS
      configuration.

PMID- 16999773
TI  - Synthesis and reactivity of 6,7-dihydrogeranylazides: reagents for primary azide
      incorporation into peptides and subsequent staudinger ligation.
AB  - Protein farnesyltransferase (PFTase) catalyzes the attachment of a geranylazide
      moiety to a peptide substrate, N-dansyl-GCVIA. Because geranylazide is actually a
      mixture of isomeric, interconverting primary and secondary azides, incorporation
      of this isoprenoid into peptides can potentially result in a corresponding
      mixture of prenylated peptides. Here, we first examined the reactivity of geranyl
      azide in a model Staudinger reaction and determined that a mixture of products is
      formed. We then describe the synthesis of 6,7-dihydrogeranylazide diphosphate and
      demonstrate that this compound allows exclusive incorporation of a primary azide
      into a peptide. The resulting azide-containing peptide was derivatized with a
      triphenylphosphine-based reagent to generate an O-alkyl imidate-linked product.
      Finally, we show, using a series of model reactions, that the Staudinger ligation
      frequently produces small amounts of O-alkyl imidate products in addition to the
      major amide-linked products. Thus, the alkoxyimidates we have observed as the
      exclusive products in the reactions of peptides containing prenylated azides also
      appear to be a common type of product formed using other azide-containing
      reactants, although at greatly reduced levels. This method for chemical
      modification of the C-terminus of a protein should be useful for a variety of
      applications in protein chemistry.

PMID- 16999774
TI  - Identification and molecular diversity of T-superfamily conotoxins from Conus
      lividus and Conus litteratus.
AB  - The T-superfamily conotoxins comprise a large and diverse group of biologically
      active peptides and are widely distributed in venom ducts of all major feeding
      types of Conus. Six novel T-superfamily peptides from the two worm-hunting cone
      snail species of Conus lividus andConus. litteratus native to Hainan were
      identified and determined to share a common signal sequence as well as a
      conserved arrangement of cysteine residues (CC-CC). The predicted mature peptides
      consist of 11-15 amino acids only. Phylogenetic analyses of new conotoxins from
      C. lividus andC. litteratus in present study and published homologue T
      superfamily sequences from the other Conus species was systematically performed.
      Phylogenetic trees, residue substitutions to view evolutionary relationships of
      the precursors' signal, propeptide, and mature toxin regions were explored, as
      well as residue frequency component and cystine codon usage. Percent divergence
      of the amino acid sequences of the signal-region exhibited high conservation,
      whereas the sequences of the mature peptides ranged from high similarity to high
      divergence between inter- and intro-species. Notably, diversity of pro-peptide
      region was also high with intermediate percent divergence between that observed
      in signal and toxin-regions. Consensus hydrophobic residues Leu, Val, Ala, Ile
      and Pro of signal regions were abundant, whereas among propeptides, basic
      residues Arg and Lys and acidic residue Asp, addition of hydrophilic residues Thr
      and Ser were abundant. Residue frequency components were hypervariable in mature
      toxin region except for highly conservative cystine frame residues. The T
      superfamily conotoxins have been previously found mainly in piscivorous and
      molluscivorous cone snails. The newly identified six T-superfamily peptides
      described in this investigation exemplify the first to be found from
      vermivorousC. lividus andC. litteratus. The elucidated cDNAs of the six toxins
      will facilitate a better understanding of the relationship between structure and
      function as well as provide a framework for their further research and
      development.

PMID- 16999775
TI  - Selection of novel nickel-binding peptides from flagella displayed secondary
      peptide library.
AB  - Nickel (Ni) performs its biological or toxic functions in nickel-protein
      coordination form. Novel Ni-binding peptides were isolated from a random
      dodecapeptide library displayed on the flagella of Escherichia coli against
      immobilized ions. On the basis of isolated sequences rich in histidine residues,
      two secondary libraries were constructed respectively. By consequent selection,
      more Ni-chelating peptides were identified and the consensus motif RHXHR (where X
      was always H) was deduced. The result suggested that not only histidine, but also
      arginine, play an important role in Ni-binding. Furthermore, two selected clones
      (1035 and 2022) were chosen for further identification. They exhibited similar
      relative binding affinity, which was about nine times that of the original
      library derived clones and statistically much more significant than the positive
      control with polyhistidine insert. Free nickel ions could almost completely
      inhibit the binding of the clones 1035 and 2022 to immobilized nickel,
      implicating that the peptides were able to chelate nickel ions. These studies
      reveal that bacterial surface displayed peptide libraries may have promising
      future potential for the development of metal bioadsorbents. Furthermore, novel
      Ni-binding peptides may provide lead molecules for Ni-chelation and applications
      thereof.

PMID- 16999776
TI  - Examination of two independent kinetic assays for determining the inhibition of
      carbonic anhydrases I and II: structure-activity comparison of sulfamates and
      sulfamides.
AB  - Enzyme inhibition assays often require deviations from physiological conditions.
      For carbonic anhydrases, procedures involving native CO(2) and non-native
      substrates have been used. We compared a native and a non-native substrate in the
      context of inhibition of human carbonic anhydrases I and II by examining various
      sulfamate and sulfamide compounds in two kinetic assays: hydration of CO(2) and
      hydrolysis of 4-nitrophenylacetate. For carbonic anhydrase II, the two assays
      consistently generated similar K(i) values, with the relative difference between
      the assays never exceeding 2.5-fold. However, for carbonic anhydrase I there was
      more variability between the two assays, with K(i) values for three compounds
      differing by more than 2.5-fold, up to eightfold. In the CO(2) hydration assay,
      some sulfamates and sulfamides exhibited mixed kinetics or partial inhibition.
      Our results indicate that K(i) or K(d) values from carbonic anhydrase assays
      involving non-native substrates should be confirmed by assays that use CO(2) (or
      HCO), to establish pharmacological relevance. From structure-activity
      comparisons, the sulfamate is more effective than the sulfamide in inhibiting
      carbonic anhydrase I and II, but the sulfamate does not confer selectivity. In
      contrast, the sulfonamide confers selectivity for carbonic anhydrase I (10- to 30
      fold). Selectivity for carbonic anhydrase II occurred with the substituted
      fructose moiety, especially the d-enantiomer (>100-fold).

PMID- 16999777
TI  - Discovery of synthetic penaeidin activity against antibiotic-resistant fungi.
AB  - Penaeidins are antimicrobial peptides from shrimp that are constituted by
      divergent classes of peptide isoforms in an individual organism. Penaeidin
      sequence variation suggests functional diversity in the host and promises
      differential activities if applied to treat infections in humans. We have
      synthesized isoform 4 of penaeidin class 3 from the Atlantic shrimp, Litopenaeus
      setiferus, by native ligation using three peptide segments. Our synthesis
      approach led to the discovery of an irreversible side reaction that was
      successfully suppressed, a discovery, which has particular relevance to the
      synthesis of cysteine-rich peptides. The antimicrobial activity of full-length
      penaeidin and the N-terminal proline-rich domain of this isoform were compared
      with the corresponding peptides of penaeidin class 4 isoform 1 using a wide range
      of bacteria and fungi. New aspects of penaeidin function are reported that
      include activity against fungi of the phylum Basidiomycota (Cryptococcus
      strains), activity against fungi that are pathogenic to humans and effectiveness
      in the context of antibiotic resistance mechanisms (Cryptococcus and Candida
      spp.). The proline-rich domain of penaeidin class 4 shows the highest relative
      antimicrobial activity, while exhibiting no cytotoxicity to human monocytes, and
      therefore stands out as a potential peptide therapeutic.

PMID- 16999780
TI  - Do social information-processing models explain aggressive behaviour by children
      with mild intellectual disabilities in residential care?
AB  - BACKGROUND: This study aimed to examine whether the social information-processing
      model (SIP model) applies to aggressive behaviour by children with mild
      intellectual disabilities (MID). The response-decision element of SIP was
      expected to be unnecessary to explain aggressive behaviour in these children, and
      SIP was expected to mediate the relation between social schemata and aggressive
      behaviour. METHOD: SIP and aggressive behaviour of 130 10- to 14-year-old
      children with MID in residential care were assessed. The fit of various SIP
      models was tested with structural equation modelling. RESULTS: The response
      decision process was found not to be necessary to explain aggressive behaviour.
      Social schemata were indirectly related to aggressive behaviour with aggressive
      response generation as mediating variable. CONCLUSIONS: Implications for SIP
      theory and intervention are discussed.

PMID- 16999781
TI  - A review of the reliability and validity of Likert-type scales for people with
      intellectual disability.
AB  - BACKGROUND: Likert-type scales are increasingly being used among people with
      intellectual disability (ID). These scales offer an efficient method for
      capturing a wide range of variance in self-reported attitudes and behaviours.
      This review is an attempt to evaluate the reliability and validity of Likert-type
      scales in people with ID. METHODS: Fifty-one studies reporting response rates,
      response bias, reliability and validity of Likert-type scales among adolescents
      and adults with ID were reviewed. RESULTS: Low response rates were found among
      adolescents and adults with moderate to profound ID, when pictorial
      representations of response alternatives were not employed, and for Likert-type
      scales with self-descriptive statements. Response bias was evident, particularly
      among adolescents and adults with moderate to profound ID. Likert-type scales
      have better reliability and validity among adolescents and adults with borderline
      IQ or mild ID. Pretests and clarifying questions increase reliability and
      validity. CONCLUSIONS: Likert-type scales should include pictorial
      representations of response alternatives, a single set of one or two word
      response descriptors, clarifying questions, and pretests, and are best used with
      adolescents and adults with borderline IQ to mild ID.

PMID- 16999782
TI  - Social climate within secure inpatient services for people with intellectual
      disabilities.
AB  - BACKGROUND: The social climate of inpatient facilities is thought to be an
      important contributor to treatment outcome. However, little research has focused
      on this construct within secure forensic services for people with intellectual
      disabilities (ID). Therefore, the objective of this study was to investigate the
      social climate of two different types of secure units ('low' secure vs. 'medium'
      secure) contained within the same facility for offenders with ID. Two hypotheses
      were generated: (1) residents would rate the social climate of the whole facility
      in a more negative direction than staff, and (2) residents and staff would rate
      the social climate of the 'low' secure unit in a more positive direction than
      that of the 'medium' secure unit. METHOD: Using a 2 (factor 'Participant' = Staff
      or Resident) x 2 (factor 'Unit' = 'Low' or 'Medium' Secure Unit) between-subjects
      design, 18 residents and 37 staff members were recruited and completed the
      Correctional Institutions Environment Scale (CIES), a measure of social climate.
      RESULTS: Residents tended to rate the units in a more positive direction than
      staff on some sub-scales. Participants rated the 'low' secure unit in a more
      positive direction than the 'medium' secure unit on two sub-scales of the CIES.
      However, on selected sub-scales there were differences. The findings of this
      study suggest that the CIES may be a valid instrument for use within forensic
      services for people with ID, and further suggests that residents and staff have
      different perceptions of the shared social climate, which may have implications
      for service development.

PMID- 16999783
TI  - People with learning disabilities in 'out-of-area' residential placements: 1.
      Policy context.
AB  - BACKGROUND: A growing shortage of residential care for people with learning
      disabilities leads to placement funded by one authority in another authority's
      area. Such out-of-area placements are governed by guidance from different
      government departments in respect of different funding streams. METHOD: This
      paper presents an analysis of this guidance and shows that it is inconsistent and
      incomplete. RESULTS AND CONCLUSION: The guidance creates a framework of
      incentives for health and social services authorities that could lead to people
      being placed out-of-area against their own best interests, with negative
      consequences for them and for the 'receiving' authorities. A companion paper uses
      interview data to examine the reasons for and effects of out-of-area placement.

PMID- 16999784
TI  - People with learning disabilities in 'out-of-area' residential placements: 2.
      Reasons for and effects of placement.
AB  - BACKGROUND: Official guidance on out-of-area placements creates incentives that
      could lead to people being placed against their own best interests, with negative
      consequences for them and for the 'receiving' authorities. METHOD: Information
      was collected for 30 people through interviews with them, their families, home
      managers and care managers. Interviews concerned resident needs, reasons for
      placement, the homes, care management arrangements, resident quality of life and
      social inclusion. Information on care standards was abstracted from official
      records. RESULTS: The main reasons for out-of-area placement were insufficient
      local services of acceptable quality, financial incentives and loss of family
      contact through prior institutionalization. The effects varied, with the most
      disabled people experiencing worst outcomes. Some aspects were worse than
      comparison studies (choice, community involvement, number of homes meeting all
      the national minimum standards), some were the same (participation, family
      visiting and other contact), and one was better (visits to families). Variation
      was also evident in the involvement of social services staff from the placing
      authority and in ease of access to local healthcare resources. CONCLUSIONS:
      Social services and health authorities should develop services locally that can
      support people with the full range of individual needs. Perverse incentives
      should be removed, perhaps by increasing the application of direct payments and
      personalized budgets.

PMID- 16999787
TI  - Race, ethnicity, and culture in child development: contemporary research and
      future directions.
AB  - The editors of this special issue reflect on the current status and future
      directions of research on race, ethnicity, and culture in child development.
      Research in the special issue disentangles race, ethnicity, culture, and
      immigrant status, and identifies mediators of sociocultural variables on
      developmental outcomes. The special issue includes important research on normal
      development in context for ethnic and racial minority children, addresses racial
      and ethnic identity development, and considers intergroup processes. The
      methodological innovations as well as challenges of current research are
      highlighted. It is recommended that future research adhere to principles of
      cultural validity described in the text.

PMID- 16999788
TI  - The legacy of Child Development's 1990 special issue on minority children: an
      editorial retrospective.
AB  - Sixteen years have passed since the publication of Child Development's Special
      Issue on Minority Children. It is suggested that the most critical legacy of the
      special issue is the conceptual and ideological zeitgeist it fostered. The issue
      set culture and ecological context in the foreground of analyses, advanced a
      cultural-variant perspective, and further discredited the deficit perspective
      that long dominated the study of ethnic minority children and families. The
      special issue is also significant for its role in shaping post-1990 research
      agenda. In addition, it underscored the need for more nuanced articulations of
      what cultural or ethnic characteristics are of special relevance for
      understanding specific domains of development and the need for well-crafted
      methodological tools with which to test these ideas.

PMID- 16999789
TI  - Revisiting the 1990 special issue on minority children: an editorial perspective
      15 years later.
AB  - The 2006 Special Issue on Race, Ethnicity, and Culture in Child Development
      occurs 15 years after the 1990 Special Issue on Minority Children and marks
      roughly 50 years since the historic 1954 Brown v. Board of Education Supreme
      Court decision. This issue provides an assessment of how researchers have
      represented development of America's diverse youth. This commentary provides a
      perspective of the progress and needs inferred from the 1990 special issue. A
      consistent theme is the necessity to link research and developmental theorizing
      with the intentions of the Brown v. Board of Education decision, as the relevant
      integration is often left to legal scholars, Whiteness studies theorists, and a
      few child-development-focused researchers (e.g., Cross, 1991; Spencer, 2005).

PMID- 16999790
TI  - Racial-ethnic identity in mid-adolescence: content and change as predictors of
      academic achievement.
AB  - Three aspects of racial-ethnic identity (REI)-feeling connected to one's racial
      ethnic group (Connectedness), being aware that others may not value the in-group
      (Awareness of Racism), and feeling that one's in-group is characterized by
      academic attainment (Embedded Achievement)-were hypothesized to promote academic
      achievement. Youth randomly selected from 3 low-income, urban schools (n=98
      African American, n=41 Latino) reported on their REI 4 times over 2 school years.
      Hierarchical linear modeling shows a small increase in REI and the predicted REI
      grades relationship. Youth high in both REI Connectedness and Embedded
      Achievement attained better grade point average (GPA) at each point in time;
      youth high in REI Connectedness and Awareness of Racism at the beginning of 8th
      grade attained better GPA through 9th grade. Effects are not moderated by race
      ethnicity.

PMID- 16999791
TI  - Perceived discrimination and the adjustment of African American youths: a five
      year longitudinal analysis with contextual moderation effects.
AB  - Longitudinal links between perceived racial discrimination and later conduct
      problems and depressive symptoms were examined among 714 African American
      adolescents who were 10-12 years old at recruitment. Data were gathered 3 times
      over a 5-year period. Hypotheses were tested via latent curve modeling and
      multiple-group latent growth modeling. Increases in perceived discrimination were
      associated with increased conduct problems and depressive symptoms. This
      association was weaker when youths received nurturant-involved parenting,
      affiliated with prosocial friends, and performed well academically. For conduct
      problems, the association was stronger for boys than for girls; for depressive
      symptoms, no gender differences emerged. The findings thus identify contextual
      variables that moderate the contribution of perceived discrimination to African
      American youths' adjustment.

PMID- 16999792
TI  - Parental interactions with Latino infants: variation by country of origin and
      English proficiency.
AB  - This study examined variation in mother-infant interactions, father engagement,
      and infant cognition as a function of country of origin, socioeconomic status,
      and English language proficiency in a national sample of Latino infants (age 9
      months) born in the United States and living with both biological parents
      (N=1,099). Differences between Mexican-American infants, who had lower mother
      infant interaction scores and less father physical play than did the other Latino
      infants, were associated with differences in acculturation (both parents' English
      proficiency). Indicators of acculturation and paternal reports of happiness with
      partner were associated with paternal engagement. Indicators of acculturation
      were also related to mother-infant interactions. Infant cognitive scores were
      associated with maternal interaction but not father engagement, and maternal but
      not paternal mental health.

PMID- 16999793
TI  - Changing children's intergroup attitudes toward refugees: testing different
      models of extended contact.
AB  - The present research evaluated an intervention, derived from the "extended
      contact hypothesis," which aimed to change children's intergroup attitudes toward
      refugees. The study (n=253) tested 3 models of extended contact among 5- to 11
      year-old children: dual identity, common ingroup identity, and decategorization.
      Children read friendship stories based upon these models featuring in- and
      outgroup members. Outgroup attitudes were significantly more positive in the
      extended contact conditions, compared with the control, and this was mediated by
      "inclusion of other in self." The dual identity intervention was the most
      effective extended contact model at improving outgroup attitudes. The effect of
      condition on outgroup intended behavior was moderated by subgroup identity.
      Implications for theoretically based prejudice-reduction interventions among
      children are discussed.

PMID- 16999794
TI  - Neighborhood matters: racial socialization of African American children.
AB  - Differences in racial socialization practices and their effects were examined in
      a sample of 241 African American 1st graders (average age 6.59 years) living in
      an urban area. Child outcomes included cognitive development, receptive language
      skills, and child problem behavior. The cultural environment of the home was
      associated with higher cognitive scores for boys living in high negative social
      climate and low social capital neighborhoods and for girls living in high social
      capital neighborhoods. The positive association of promotion of mistrust and
      child behavior problems was magnified in neighborhoods that had low levels of
      social capital. A high negative social climate in the neighborhood attenuated the
      positive association between preparation for bias/promotion of mistrust and
      externalizing problems.

PMID- 16999795
TI  - Cultural variations in the socialization of young children's anger and shame.
AB  - Tamang and Brahman Nepali children have culturally specific emotion scripts that
      may reflect different emotion socialization experiences. To study emotion
      socialization, the child-adult interactions of 119 children (3-5 years old) were
      observed and 14 village elders were interviewed about child competence in Tamang
      and Brahman villages. Tamang rebuke the angry child but reason with and yield to
      the child who appears ashamed. Brahmans respond to child anger with reasoning and
      yielding but ignore shame. Tamang practices are consistent with their view that
      competent children are socially graceful and never angry. Brahman practices
      appear to be consistent with the privileges and duties of high caste status. The
      roles of cultural heritage, religious differences, and majority and minority
      status in emotion socialization are discussed.

PMID- 16999796
TI  - Relations between parent-child acculturation differences and adjustment within
      immigrant Chinese families.
AB  - The relations between parent and child acculturation and family and child
      adjustment were examined among 91 immigrant Chinese families in Canada with early
      adolescents (average age of 12). Acculturation was assessed in public (e.g.,
      language use) and private (e.g., values) domains separately in Chinese and
      Canadian cultures. With one exception, interactions between parent and child
      acculturation in Canadian domains were unrelated to adjustment (conflict
      intensity, depressive feelings, and achievement motivation). Interactions in
      Chinese domains were more clearly associated with adjustment. Specifically,
      mother-child interactions in Chinese public domains and father-child interactions
      in the Chinese private domain predicted adjustment. In all interactions, when
      parents were strongly orientated toward Chinese culture, lower levels of Chinese
      orientation among children were associated with lower adjustment.

PMID- 16999797
TI  - From American city to Japanese village: a cross-cultural investigation of
      implicit race attitudes.
AB  - This study examined the development of implicit race attitudes in American and
      Japanese children and adults. Implicit ingroup bias was present early in both
      populations, and remained stable at each age tested (age 6, 10, and adult).
      Similarity in magnitude and developmental course across these 2 populations
      suggests that implicit intergroup bias is an early-emerging and fundamental
      aspect of human social cognition. However, implicit race attitudes toward favored
      outgroups are more positive in older than in younger participants, indicating
      that "cultural prestige" enjoyed by a group moderates implicit bias as greater
      knowledge of group status is acquired. These results demonstrate (a) the ready
      presence, (b) early cultural invariance, and (c) subsequent cultural moderation
      of implicit attitudes toward own and other groups.

PMID- 16999798
TI  - Parental control in Latino families: an integrated review of the literature.
AB  - Using social information processing and cultural change models as explanatory
      frameworks, this article reviews the literature on Latino parental control and
      its implications for child development. It is argued that the use of parental
      control in Latino families may have motivational roots in cultural childrearing
      goals such as familismo (familism), respeto (respect), and educacion (moral
      education). Consideration of these underpinnings, in conjunction with
      psychological and methodological issues, helps to explain variability in the use
      of Latino parental control and its effect on child development. Recommendations
      for future research include refinement of control and acculturation instruments,
      and attention to both contextual and individual variables.

PMID- 16999799
TI  - Racial self-categorization in adolescence: multiracial development and social
      pathways.
AB  - Research on multiracial individuals is often cross-sectional, obscuring the fluid
      nature of multiracial self-categorization across time. Pathways of racial self
      identification are developed from a nationally representative sample of
      adolescents aged 14-18, measured again 5 years later. A significant proportion of
      multiracial adolescents change racial self-identification across time. Youth who
      ever report being multiracial are 4 times as likely to switch self-identification
      as to report consistent multiracial identities. Across this time, more
      multiracial adolescents either add a racial category (diversify) or subtract one
      (consolidate) than maintain consistent multiracial self-categorization.
      Exploratory multinomial analyses show few differences between these pathways on
      select psychological and social characteristics. Results lend quantitative
      support to qualitative studies indicating the fluidity of racial self
      categorization.

PMID- 16999800
TI  - A longitudinal investigation of personality and social adjustment among Chinese
      American and European American adolescents.
AB  - A 2-wave longitudinal study of personality in adolescence was conducted with data
      obtained at ages 12 and 17 years from approximately 60 European American and 60
      second-generation Chinese American youth. At Time 1 they completed the Children's
      Personality Questionnaire and at Time 2 they completed the High School
      Personality Questionnaire and self-report measures of high school grades,
      depression, and self-esteem. Chinese American and European American adolescents
      became more similar to each other over time through developmental and
      acculturative processes. Adolescents of both ethnicities increased in
      Extraversion and Independence. Despite this general trend, the Chinese American
      youth continued to report lower levels of Extraversion than European American
      youth. Extraversion and Anxiety predicted school grades for European Americans
      and psychological adjustment for Chinese Americans.

PMID- 16999801
TI  - Classroom contextual effects of race on children's peer nominations.
AB  - Black children generally receive poorer sociometric nominations compared with
      Whites. This effect is not fully understood because Black children rarely hold a
      classroom majority and teachers' race is rarely investigated. Research from a
      person-environment perspective suggests that the effects of children's race
      depend on the racial composition of the classroom and society's racial attitudes.
      Sociometric nominations were obtained from 1,268 5th graders, between 9 and 11
      years old (53% Black), across 57 classrooms (3-95% Black students). Half of the
      teachers were Black. The results indicated that ratings of Black children were
      more influenced by the racial context of classrooms than were ratings of White
      children. The implications of this study are discussed in relation to group
      dynamics and racial discrimination.

PMID- 16999802
TI  - Ethnic identity and the daily psychological well-being of adolescents from
      Mexican and Chinese backgrounds.
AB  - Protective effects of ethnic identity on daily psychological well-being were
      examined in a sample of 415 ninth graders from Mexican and Chinese backgrounds.
      Utilizing daily diary assessments and multilevel modeling, adolescents with a
      greater regard for their ethnic group exhibited greater levels of daily happiness
      and less daily anxiety averaged over the 2-week study period. Ethnic regard
      moderated the daily association between normative stressful demands and
      happiness, and between stressful demands and happiness experienced 1 day after
      stressors occurred. Moderating effects were significant even after controlling
      for self-esteem. Although no buffering effects of ethnic centrality were found,
      the results point to the positive influence of ethnic regard in the daily lives
      of adolescents from ethnic minority backgrounds.

PMID- 16999803
TI  - Social cognition in context: validating a cartoon-based attributional measure for
      urban girls.
AB  - Standard approaches to the development of psychological measures emphasize the
      role of the research team in identifying constructs, generating and retaining
      items, and establishing psychometric soundness. Although there are a number of
      strengths associated with these methods, the resulting measures may not be
      culturally sensitive to minority cultural groups. In order to address this need,
      the authors partnered with African American inner-city 3rd- and 4th-grade girls
      (predominantly 9- and 10-year-olds) to design and validate a cartoon-based
      hostile attributional bias measure that is developmentally and culturally
      sensitive. This paper illustrates how a partnership-based research model can be
      used to design measurement tools sensitive to the ways in which developmental
      processes are influenced by an urban, low-income, ecological context.

PMID- 16999804
TI  - Immigrant differences in school-age children's verbal trajectories: a look at
      four racial/ethnic groups.
AB  - This study explored inter- and intraindividual immigrant group differences in
      children's English verbal ability over ages 6-16 in 4 racial/ethnic groups-White
      Americans, Black Americans, Mexican Americans, and Puerto Ricans (N=2,136).
      Although all children's mean verbal scores increased with age, immigrant children
      (except for Black Americans) had lower scores than respective nonimmigrant
      children. In contrast, immigrant children (except for Mexican Americans) had more
      persistent verbal growth into adolescence than respective nonimmigrant children.
      Family resources moderately accounted for immigrant differences in children's
      mean verbal scores only. The findings support different theoretical models for
      understanding inter- and intraindividual immigrant differences in achievement.
      Mexican-American immigrants and Black American nonimmigrants were struggling and
      merit policy attention.

PMID- 16999805
TI  - Intergroup attitudes of European American children attending ethnically
      homogeneous schools.
AB  - Intergroup attitudes were assessed in European American 1st-grade (M=6.99 years,
      SD=0.32) and 4th-grade (M=10.01 years, SD=0.36) children (N=138) attending
      ethnically homogeneous schools to test hypotheses about racial biases and
      interracial friendships. An Ambiguous Situations Task and an Intergroup Contact
      Assessment were administered to all participants. Unlike previous findings with
      European American children attending heterogeneous schools, children rated
      minority perpetrators more negatively than majority perpetrators, and friendship
      as less likely when a minority than a majority perpetrator was portrayed. These
      findings suggest that intergroup contact contributes to racial bias in children's
      interpretations of peer dyadic encounters and to judgments about interracial
      friendships.

PMID- 16999806
TI  - Mothers' and fathers' racial socialization in African American families:
      implications for youth.
AB  - Mothers' and fathers' cultural socialization and bias preparation with older
      (M=13.9 years) and younger (M=10.31 years) siblings were studied in 162 two
      parent, African American families. Analyses examined whether parental warmth and
      offspring age and gender were linked to parental practices and whether parents'
      warmth, spouses' racial socialization, or youth age or gender moderated links
      between racial socialization and youth outcomes. Parental warmth was linked to
      parents' socialization. Mothers engaged in more socialization with older
      offspring, and fathers more with sons. Mothers' cultural socialization was
      positively related to youth ethnic identity and fathers' was negatively related
      to youth depression symptoms. Youth exhibited a lower locus of control when
      mothers were high but fathers were low in racial socialization.

PMID- 16999807
TI  - Longitudinal trajectories of ethnic identity among urban Black and Latino
      adolescents.
AB  - The current study modeled developmental trajectories of ethnic identity
      exploration and affirmation and belonging from middle to late adolescence (ages
      15-18) and examined how these trajectories varied according to ethnicity, gender,
      immigrant status, and perceived level of discrimination. The sample consisted of
      135 urban low-income Black and Latino adolescents (42% male, 34% Black, 66%
      Latino). Consistent with developmental theory, individual growth modeling
      identified an average quadratic trajectory of ethnic identity exploration
      characterized by decelerating levels of exploration after 10th grade. However,
      ethnicity and perceived discrimination by peers moderated this pattern. No
      uniform growth pattern in affirmation was found and Black and Latino adolescents
      displayed equally high levels of affirmation over time.

PMID- 16999808
TI  - The status model of racial identity development in African American adolescents:
      evidence of structure, trajectories, and well-being.
AB  - Although the identity formation model is widely used to assess adolescent ethnic
      identity development, the model propositions have rarely been tested. The
      existence of the identity statuses (diffuse, foreclosed, moratorium, achieved),
      the proposed developmental trajectories, and whether youth in the achieved status
      report higher levels of psychological well-being were examined among a
      longitudinal sample of 224 African American adolescents, aged 11-17. Cluster
      analyses were used to create 4 identity statuses consistent with the theoretical
      model at both time points. The findings indicate that some adolescents
      progressed, while others regressed or remained constant across time periods.
      Lastly, the results generally support the assumption that individuals in the
      achieved status had the highest levels of psychological well-being at both time
      periods.

PMID- 16999809
TI  - Contextual influences on Latino adolescent ethnic identity and academic outcomes.
AB  - This study examined the association between 3 components of ethnic identity
      (exploration, resolution, and affirmation) and factors related to family,
      neighborhood, and individual characteristics. The purpose was to identity factors
      that are positively associated with adolescent ethnic identity among a sample of
      187 Latino adolescents with a mean age of 14.61. The findings suggested that
      family ethnic socialization was directly associated with exploration and
      resolution, but not ethnic affirmation. Analyses with moderator variables
      suggested that associations between family ethnic socialization and ethnic
      affirmation varied based on parental behaviors and neighborhood characteristics.
      The results also suggested that ethnic affirmation, but not exploration or
      resolution, was positively associated with teacher reports of school performance.

PMID- 16999810
TI  - Unpacking immigration in youths' academic and occupational pathways.
AB  - This study sought to unpack how immigration is associated with youths'
      educational choices during the transition to college and adulthood. Surveys and
      school records were collected on 789 youth (ages 18-25) with Asian Pacific,
      Latino, African/Afro-Caribbean, and European backgrounds. The results indicated
      generational differences in educational choices, such that children of immigrants
      chose courses of study with higher math and science content than that of their
      peers with U.S.-born parents. Mediation analyses indicated that children of
      immigrants reported higher social and economic aspirations than did their peers,
      and their economic aspirations accounted for part of the generational difference
      in educational choices. Generational differences in educational choices were also
      mediated by verbal achievement test scores and perceived English skills.

PMID- 16999811
TI  - A window into different cultural worlds: young children's everyday activities in
      the United States, Brazil, and Kenya.
AB  - A powerful means to understand young children's normative development in context
      is to examine their everyday activities. The daily activities of 79 children (3
      years old) were observed, for 20 hr each, in their usual settings. Children were
      selected from 4 cultural groups: European American and African American
      (Greensboro, United States), Luo (Kisumu, Kenya), and European descent (Porto
      Alegre, Brazil), evenly divided by social class. Examining children's naturally
      occurring engagement in school-relevant activities, both in and out of child
      care, revealed the importance of ecological context. The variation in activities
      was not explainable simply by cultural group (including race within the United
      States) or social class, but by the intersection of culture and class. The
      developmental implications of these findings are discussed.

PMID- 16999812
TI  - The nature and correlates of Mexican-American adolescents' time with parents and
      peers.
AB  - Drawing on cultural-ecological and person-environment fit perspectives, this
      study examined links among Mexican-American adolescents' time with peers and
      parents, parents' cultural orientations, and adolescents' psychosocial adjustment
      and cultural orientations. Participants were 492 Mexican-American adolescents
      (Ms=15.7 and 12.8 years for older siblings and younger siblings) and their
      parents in 246 families. Family members described their family relationships,
      cultural orientations, and psychosocial functioning in home interviews, and time
      use data were collected during a series of nightly phone calls. Mexican-American
      adolescents spent the majority of their peer time with Mexican youth. Some
      support was found for the hypothesis that the mismatch between parents' cultural
      orientations and adolescents' peer involvement is linked to adolescents'
      psychosocial functioning.

PMID- 16999813
TI  - Developmental trajectories of personal and collective self-concept among American
      Indian adolescents.
AB  - Developmental trajectories of personal and collective self-concept were examined
      among American Indian adolescents. Personal self-concept (self-esteem) and
      collective self-concept (American Indian identity, Euro-American identity,
      community-mindedness) were assessed 6 times over 3 years in 4 cohorts of
      adolescents from 3 American Indian cultural groups (N=1,252). An accelerated
      longitudinal design was used to estimate developmental trajectories from 14 to 19
      years; parallel-process and covariate models were used to examine variation in
      trajectories. Both personal and collective self-concepts were generally positive
      and showed small gains; they were moderately related to one another and
      differentially related to cultural group, gender, and perceived social support.
      The findings highlight the complexity of self-concept for American Indian youth
      and the significance of both personal and collective identity.

PMID- 16999814
TI  - African American racial identity across the lifespan: identity status, identity
      content, and depressive symptoms.
AB  - Cluster analytic methods were used to create 4 theorized ethnic identity statuses
      (achieved, foreclosed, moratorium, and diffused) among 940 African American
      adolescents (13-17 years old), college students (18-23 years old), and adults (27
      78 years old). Evidence for the existence of 4 identity statuses was found across
      the 3 age groups. The distribution of individuals differed by age group, with the
      older participants disproportionately occupying the more mature statuses.
      Identity status was related to identity content such that achieved individuals
      reported higher levels of racial centrality and private regard. Finally, there
      was a significant interaction between developmental age group and identity status
      for depressive symptoms such that diffused college students reported higher
      symptoms than achieved college students. No status differences were found for the
      other 2 age groups.

PMID- 16999816
TI  - Progesterone receptor isoforms as a prognostic marker in human endometrial
      carcinoma.
AB  - The possible role of specific progesterone receptor (PR) isoforms (PRA and PRB)
      as predictive factors in endometrial carcinoma is unclear. The present study was
      undertaken to evaluate the clinical significance of intratumoral PR isoform
      status in patients with endometrioid endometrial carcinoma. We studied 103 cases
      of endometrioid endometrial carcinoma using immunohistochemistry. We correlated
      the findings with various clinicopathological parameters of the patients. PRA and
      PRB immunoreactivity was detected in 51/103 (48.5%) and 79/103 (76.7%) of
      carcinoma cases, respectively. A significant positive correlation was detected
      between the status of PRB immunoreactivity and the amount of PRB mRNA by real
      time reverse transcription-polymerase chain reaction (P = 0.012). PR isoform
      expression was significantly lower in the cases with higher histological grade (P
      = 0.0001 and P = 0.002, for PRA and PRB, respectively). Cases that were negative
      for either one or both PR isoforms were significantly associated with shorter
      disease-free and overall survival of the patients. The absence of either one or
      both of these two PR isoforms was detected in all nine patients who died
      (100.0%), whereas the absence of these immunoreactivities was detected only in 43
      of 94 (45.7%) patients who had lived during the same period. In addition,
      multivariate analysis demonstrated that an absence of PRA immunoreactivity was an
      independent risk factor in disease-free survival of the patients (P = 0.0258).
      The results of our study demonstrated that loss or absence of PR isoform
      expression determined by immunohistochemistry could become an important
      prognostic indicator in patients with endometrioid endometrial carcinoma.

PMID- 16999817
TI  - Downregulation of circadian clock genes in chronic myeloid leukemia: alternative
      methylation pattern of hPER3.
AB  - Disruption of circadian rhythm is believed to play a critical role in cancer
      development. To gain further insights into the roles of circadian genes in
      chronic myeloid leukemia (CML), we analyzed peripheral blood from 53 healthy
      individuals and 35 CML patients for the expression of the nine circadian genes.
      The expression levels of hPER1, hPER2, hPER3, hCRY1, hCRY2 and hBMAL1 were
      significantly impaired in both chronic phase and blastic crisis of CML cases
      compared with those in healthy individuals (P < 0.001). Methylation studies in
      the promoter areas of these six genes revealed that only the CpG sites of the
      hPER3 gene were methylated in all of the CML patients, and the methylated CpG
      frequencies differed significantly in patients at blastic crisis (8.24 +/- 0.73)
      or at chronic phase (4.48 +/- 0.48). The CpG sites of the hPER2 gene were also
      methylated in 40% of the CML patients. No mutation was found within the coding
      region of hPER3 in CML cases. Our results suggest that the downregulated hPER3
      expression in CML is correlated with the inactivation of hPER3 by methylation.

PMID- 16999818
TI  - Antivascular effects of TZT-1027 (Soblidotin) on murine Colon26 adenocarcinoma.
AB  - We investigated the ability of TZT-1027 (Soblidotin), a novel antimicrotubule
      agent, to induce antivascular effects, because most vascular targeting agents
      that selectively disrupt tumor vasculature also inhibit tubulin polymerization.
      Treatment with 10(-7) g/mL TZT-1027 rapidly disrupted the microtubule
      cytoskeleton in human umbilical vascular endothelial cells (HUVEC), and
      significantly enhanced vascular permeability in HUVEC monolayers. In addition,
      single intravenous administration of 2 mg/kg TZT-1027 to mice bearing Colon26
      tumors significantly reduced tumor perfusion and caused extravascular leakage of
      erythrocytes 1 h after administration. Subsequently, thrombus formation with
      deposition of fibrin and tumor necrosis was observed 3 and 24 h after
      administration, respectively. These results strongly suggest that TZT-1027
      possesses antivascular effects. TZT-1027 induced apoptosis not only in HUVEC but
      also in C26 cancer cells (cell line of Colon26 solid tumor) in vitro, suggesting
      it exerts direct cytotoxicity against tumor cells in addition to its antivascular
      effects. A single intravenous administration of 1, 2 and 4 mg/kg TZT-1027
      significantly prolonged the survival of mice with advanced-stage Colon26 tumors
      in a dose-dependent manner. Furthermore, TZT-1027 itself less markedly enhanced
      the permeability of normal vessels, but was additive with vascular endothelial
      growth factor, indicating the possibility that TZT-1027 selectively exerts its
      activity on tumor vessels. In summary, these results suggest that TZT-1027 exerts
      both an indirect antivascular effect and a direct cytotoxic effect, resulting in
      strong antitumor activity against advanced-stage tumors, and that TZT-1027 may be
      useful clinically for treating solid tumors.

PMID- 16999819
TI  - Matriptase activates stromelysin (MMP-3) and promotes tumor growth and
      angiogenesis.
AB  - Matriptase/MT-SP1, a type II membrane serine protease widely expressed in normal
      epithelial cells and human carcinoma cells, is thought to be involved in cancer
      progression. To clarify this possibility, we overexpressed exogenous matriptase
      in the human stomach cancer cell line AZ521. In vitro, the matriptase
      transfectant (Mat-AZ521) and the control transfectant (Mock-AZ521) showed a
      similar growth rate, although the saturation cell density was significantly
      higher with the Mat-AZ521. When implanted into nude mice subcutaneously or
      intraperitoneally, Mat-AZ521 cells grew faster and produced much larger solid
      tumors than Mock-AZ521 cells. The overexpression of matriptase in AZ521 cells
      shortened the survival time of tumor-bearing mice. Histological analysis showed
      that both the number and the size of blood vessels in tumor tissues were
      significantly higher in the Mat-AZ521 tumors than the Mock-AZ521 ones. Moreover,
      it was found that purified matriptase activated one of the important matrix
      metalloproteinases, stromelysin (MMP-3). These results suggest the possibility
      that the matriptase-dependent activation of MMP-3, as well as the direct activity
      of matriptase, promotes tumor growth and angiogenesis by enhancing extracellular
      matrix degradation in tumor cell microenvironments.

PMID- 16999820
TI  - Actin-binding protein filamin A is displayed on the surface of human
      neuroblastoma cells.
AB  - We previously reported the identification of natural human IgM antibodies, which
      recognize a M(r) 260 000 surface protein (NB-p260) and induce both complement
      mediated cytotoxicity and apoptosis of human neuroblastoma cells. NB-p260 was
      shown to belong to the family of filamin proteins. Filamin A is a high molecular
      weight actin-binding protein, previously thought to be only located
      intracellularly. Here we show that NB cells as well as three NB-unrelated human
      cell lines express filamin A also on the cell surface. Our findings suggest new
      biological functions for filamins, including a role as mediators in anti-NB IgM
      induced apoptosis, and they add to the growing body of evidence of the
      interaction of cytoskeletal proteins with the extracellular matrix.

PMID- 16999821
TI  - Site-directed mutagenesis of selected residues at the active site of aryl-alcohol
      oxidase, an H2O2-producing ligninolytic enzyme.
AB  - Aryl-alcohol oxidase provides H(2)O(2) for lignin biodegradation, a key process
      for carbon recycling in land ecosystems that is also of great biotechnological
      interest. However, little is known of the structural determinants of the
      catalytic activity of this fungal flavoenzyme, which oxidizes a variety of
      polyunsaturated alcohols. Different alcohol substrates were docked on the aryl
      alcohol oxidase molecular structure, and six amino acid residues surrounding the
      putative substrate-binding site were chosen for site-directed mutagenesis
      modification. Several Pleurotus eryngii aryl-alcohol oxidase variants were
      purified to homogeneity after heterologous expression in Emericella nidulans, and
      characterized in terms of their steady-state kinetic properties. Two histidine
      residues (His502 and His546) are strictly required for aryl-alcohol oxidase
      catalysis, as shown by the lack of activity of different variants. This fact,
      together with their location near the isoalloxazine ring of FAD, suggested a
      contribution to catalysis by alcohol activation, enabling its oxidation by flavin
      adenine dinucleotide (FAD). The presence of two aromatic residues (at positions
      92 and 501) is also required, as shown by the conserved activity of the Y92F and
      F501Y enzyme variants and the strongly impaired activity of Y92A and F501A. By
      contrast, a third aromatic residue (Tyr78) does not seem to be involved in
      catalysis. The kinetic and spectral properties of the Phe501 variants suggested
      that this residue could affect the FAD environment, modulating the catalytic rate
      of the enzyme. Finally, L315 affects the enzyme k(cat), although it is not
      located in the near vicinity of the cofactor. The present study provides the
      first evidence for the role of aryl-alcohol oxidase active site residues.

PMID- 16999822
TI  - Engineering and characterization of human manganese superoxide dismutase mutants
      with high activity and low product inhibition.
AB  - Human manganese superoxide dismutase is a mitochondrial metalloenzyme that is
      involved in protecting aerobic organisms against superoxide toxicity, and has
      been implicated in slowing tumor growth. Unfortunately, this enzyme exhibits
      strong product inhibition, which limits its potential biomedical applications.
      Previous efforts to alleviate human manganese superoxide dismutase product
      inhibition utilized rational protein design and site-directed mutagenesis. These
      efforts led to variants of human manganese superoxide dismutase at residue 143
      with dramatically reduced product inhibition, but also reduced catalytic activity
      and efficiency. Here, we report the use of a directed evolution approach to
      engineer two variants of the Q143A human manganese superoxide dismutase mutant
      enzyme with improved catalytic activity and efficiency. Two separate activity
      restoring mutations were found--C140S and N73S--that increase the catalytic
      efficiency of the parent Q143A human manganese superoxide dismutase enzyme by up
      to five-fold while maintaining low product inhibition. Interestingly, C140S is a
      context-dependent mutation, and the C140S-Q143A human manganese superoxide
      dismutase did not follow Michaelis-Menten kinetics. The re-engineered human
      manganese superoxide dismutase mutants should be useful for biomedical
      applications, and our kinetic and structural studies also provide new insights
      into the structure-function relationships of human manganese superoxide
      dismutase.

PMID- 16999823
TI  - Staphylococcus aureus protein A binding to von Willebrand factor A1 domain is
      mediated by conserved IgG binding regions.
AB  - Protein A (Spa) is a surface-associated protein of Staphylococcus aureus best
      known for its ability to bind to the Fc region of IgG. Spa also binds strongly to
      the Fab region of the immunoglobulins bearing V(H)3 heavy chains and to von
      Willebrand factor (vWF). Previous studies have suggested that the protein A-vWF
      interaction is important in S. aureus adherence to platelets under conditions of
      shear stress. We demonstrate that Spa expression is sufficient for adherence of
      bacteria to immobilized vWF under low fluid shear. The full length recombinant Ig
      binding region of protein A, Spa-EDABC, fused to glutathione-S-transferase (GST),
      bound recombinant vWF in a dose-dependent and saturable fashion with half maximal
      binding of about 30 nm in immunosorbent assays. Full length-Spa did not bind
      recombinant vWF A3 domain but displayed binding to recombinant vWF domains A1 and
      D'-D3 (half maximal binding at 100 nm and 250 nm, respectively). Each recombinant
      protein A Ig-binding domain bound to the A1 domain in a similar manner to the
      full length-Spa molecule (half maximal binding 100 nm). Amino acid substitutions
      were introduced in the GST-SpaD protein at sites known to be involved in IgG Fc
      or in V(H)3 Fab binding. Mutants altered in residues that recognized IgG Fc but
      not those that recognized V(H)3 Fab had reduced binding to vWF A1 and D'-D3. This
      indicated that both vWF regions recognized a region on helices I and II that
      overlapped the IgG Fc binding site.

PMID- 16999824
TI  - Inactivation of the group A Streptococcus regulator srv results in chromosome
      wide reduction of transcript levels, and changes in extracellular levels of Sic
      and SpeB.
AB  - Group A Streptococcus is characterized by the ability to cause a diverse number
      of human infections including pharyngitis, necrotizing fasciitis, toxic shock
      syndrome, and acute rheumatic fever, yet the regulation of streptococcal genes
      involved in disease processes and survival in the host is not completely
      understood. Genome scale analysis has revealed a complex regulatory network
      including 13 two-component regulatory systems and more than 100 additional
      putative regulators, the majority of which remain uncharacterized. Among these is
      the streptococcal regulator of virulence, Srv, the first Group A Streptococcus
      member of the Crp/Fnr family of transcriptional regulators. Previous work
      demonstrated that the loss of srv resulted in a significant decrease in Group A
      Streptococcus virulence. To begin to define the gene products influenced by Srv,
      we combined microarray and two-dimensional gel electrophoresis analysis. Loss of
      srv results in a chromosome wide reduction of gene transcription and changes in
      the production of the extracellular virulence factors Sic (streptococcal
      inhibitor of complement) and SpeB (cysteine proteinase). Sic levels are reduced
      in the srv mutant, whereas the extracellular concentration and activity of SpeB
      is increased. These data link Srv to the increasingly complex GAS regulatory
      network.

PMID- 16999825
TI  - Comparative PCR-based restriction fragment length polymorphism analysis of the
      plasmid gene orf3 of Chlamydia trachomatis and Chlamydia psittaci.
AB  - The BfaI digestion of PCR-based restriction fragment length polymorphism analysis
      of the plasmid orf3 of Chlamydia trachomatis and Chlamydia psittaci provided
      evidence for two distinct restriction patterns, respectively. The nucleotide
      sequences of orf3 genes confirmed these differences. Serum antibodies against
      recombinant C. psittaci protein (pgp3) encoded by orf3 were detected both in
      pigeons with C. psittaci infection and in a human patient with psittacosis.

PMID- 16999826
TI  - SecA2 is distinct from SecA in immunogenic specificity, subcellular distribution
      and requirement for membrane anchoring in Streptococcus parasanguis.
AB  - A secA2 gene is present in the genomes of a wide variety of Gram-positive
      bacteria. In Streptococcus parasanguis, a primary colonizer of the tooth surface,
      secA2 is involved in the secretion of a small group of proteins including the
      fimbrial adhesin, Fap1. Although the substrate specificity is different, SecA2 is
      predicted to be similar to SecA in structure and function based on the homology
      between these two proteins. In this study, polyclonal antibodies against SecA2
      and SecA did not cross-react with each other, indicating that these two proteins
      possessed distinct immunogenic epitopes. Fractionation analysis demonstrated that
      SecA2 was not evenly distributed between the cytoplasmic membrane and the
      cytoplasm as was noted for SecA. SecA2 was associated with the membrane in the
      wild type and in secA2 mutants with different regions deleted. The subcellular
      distribution of SecA2 was not dependent on secY2, suggesting that the membrane
      association is not through SecY2. These data suggested that SecA2 is distinct
      from SecA in many respects such as substrate specificity, immunogenic
      specificity, subcellular distribution and requirement for membrane anchoring.

PMID- 16999827
TI  - A transcriptome analysis of isoamyl alcohol-induced filamentation in yeast
      reveals a novel role for Gre2p as isovaleraldehyde reductase.
AB  - A transcriptome analysis was performed of Saccharomyces cerevisiae undergoing
      isoamyl alcohol-induced filament formation. In the crucial first 5 h of this
      process, only four mRNA species displayed strong and statistically significant
      increases in their levels of more than 10-fold. Two of these (YEL071w/DLD3 and
      YOL151w/GRE2) appear to play important roles in filamentation. The biochemical
      activities ascribed to these two genes (d-lactate dehydrogenase and methylglyoxal
      reductase, respectively) displayed similarly timed increases to those of their
      respective mRNAs. Mutants carrying dld3 mutations displayed reduced filamentation
      in 0.5% isoamyl alcohol and needed a higher concentration of isoamyl alcohol to
      effect more complete filament formation. Hence, DLD3 seems to be required for a
      full response to isoamyl alcohol, but is not absolutely essential for it. Mutants
      carrying gre2 mutations were derepressed for filament formation and formed large,
      invasive filaments even in the absence of isoamyl alcohol. These results indicate
      a previously unsuspected and novel role for the GRE2 gene product as a suppressor
      of filamentation by virtue of encoding isovaleraldehyde reductase activity.

PMID- 16999829
TI  - Unexpected twist: harnessing the energy in positive supercoils to control
      telomere resolution.
AB  - Negative DNA supercoiling is an important conformational property of bacterial
      DNA that plays a significant role in a wide variety of DNA transactions. In
      contrast, positive DNA supercoiling is a by-product of cellular processes that
      involve helical unwinding or movement of DNA by a fixed translocase, and has
      generally been considered a necessary evil requiring removal. We now report the
      first evidence suggesting a physiological role for positive supercoiling; this
      occurs in telomere resolution in the related Lyme disease and relapsing fever
      Borrelia spirochetes. Telomere resolution is the process whereby covalently
      closed hairpin telomeres are generated from replicative intermediates by the
      telomere resolvase, ResT. We observe a 20-fold and greater stimulation of the
      reaction by positive supercoiling, which facilitates formation of a previously
      unobserved reaction intermediate. Our data suggest the possibility that the free
      energy of positive supercoiling, a resource with no previously described cellular
      function, may be harnessed and utilized as a regulator of post-replication
      events.

PMID- 16999828
TI  - Levels of expression of complement regulatory proteins CD46, CD55 and CD59 on
      resting and activated human peripheral blood leucocytes.
AB  - The cell surface complement regulatory (CReg) proteins CD46, CD55 and CD59 are
      widely expressed on human lymphoid and non-lymphoid cells. This study aimed to
      compare systematically levels of CReg expression by different leucocyte subsets
      and to determine whether levels were increased following activation in vitro.
      Levels of each CReg protein were similar on freshly isolated monocytes and all
      major lymphocyte subsets, except that CD4(+) cells expressed significantly less
      CD46 than CD8(+) cells (P < 0.05) while the reverse was observed for CD55 (P <
      0.02). CD56(+) cells, predominantly natural killer cells, expressed significantly
      lower levels of CD59 than T cells (P < 0.02). CD45RO(+) cells had higher levels
      of surface CD46 and CD59, but lower levels of CD55, than CD45RO(-) cells (P <
      0.02); CD25(+) cells also expressed significantly less CD55 than CD25(-) cells (P
      < 0.002). Neutrophils expressed higher levels of CD59, but lower levels of CD55,
      than monocytes. Following activation with phytohaemagglutinin, CD46 was up
      regulated on all leucocyte subsets with the exception of CD56(+) cells. Both CD55
      and CD59 were also markedly up-regulated on monocytes, and CD55 expression was
      greater on CD8(+) than CD4(+) cells following activation (P < 0.02).
      Lipopolysaccharide treatment did not significantly alter B-cell expression of
      CReg proteins whereas CD55 and CD59, but not CD46, were significantly up
      regulated on monocytes (P < 0.02). These observations that CReg proteins are up
      regulated on certain activated leucocyte subsets indicate that levels would be
      increased following immune responses in vivo. This could enhance both protection
      against local complement activation at inflammatory sites and also the
      immunoregulatory properties of these leucocytes.

PMID- 16999830
TI  - Pre-replication assembly of E. coli replisome components.
AB  - The localization of SeqA, thymidylate synthase, DnaB (helicase) and the DNA
      polymerase components alpha and tau, has been studied by immunofluorescence
      microscopy. The origin has been labelled through GFP-LacI bound near oriC. SeqA
      was located in the cell centre for one replication factory (RF) and at 1/4 and
      3/4 positions in pre-divisional cells harbouring two RFs. The transition of
      central to 1/4 and 3/4 positions of SeqA appeared abrupt. Labelled thymidylate
      synthetase was found all over the cell, thus not supporting the notion of a dNTP
      synthesizing complex exclusively localized near the RF. More DnaB, alpha and tau
      foci were found than expected. We have hypothesized that extra foci arise at pre
      replication assembly sites, where the number of sites equals the number of
      origins, i.e. the number of future RFs. A reasonable agreement was found between
      predicted and found foci. In the case of multifork replication the number of foci
      appeared consistent with the assumption that three RFs are grouped into a higher
      order structure. The RF is probably separate from the foci containing SeqA and
      the hemi-methylated SeqA binding sites because these foci did not coincide
      significantly with DnaB as marker of the RF. Co-labelling of DnaB and oriC
      revealed limited colocalization, indicating that DnaB did not yet become
      associated with oriC at a pre-replication assembly site. DnaB and tau co-labelled
      in the cell centre, though not at presumed pre-replication assembly sites. By
      contrast, alpha and tau co-labelled consistently suggesting that they are already
      associated before replication starts.

PMID- 16999831
TI  - Roles for DNA supercoiling and the Fis protein in modulating expression of
      virulence genes during intracellular growth of Salmonella enterica serovar
      Typhimurium.
AB  - Adaptation of bacterial pathogens to an intracellular environment requires
      resetting of the expression levels of a wide range of both virulence and
      housekeeping genes. We investigated the possibility that changes in DNA
      supercoiling could modulate the expression of genes known to be important in the
      intracellular growth of the pathogen Salmonella enterica serovar Typhimurium. Our
      data show that DNA becomes relaxed when Salmonella grows in murine macrophage but
      not in epithelial cells, indicating that DNA supercoiling plays a role in
      discrimination between two types of intracellular environment. The ssrA
      regulatory gene within the SPI-2 pathogenicity island that is required for
      survival in macrophage was found to be upregulated by DNA relaxation. This
      enhancement of expression also required the Fis nucleoid-associated protein.
      Manipulating the level of the Fis protein modulated both the level of DNA
      supercoiling and ssrA transcription. We discuss a model of bacterial
      intracellular adaptation in which Fis and DNA supercoiling collaborate to fine
      tune virulence gene expression.

PMID- 16999832
TI  - A STE12 homologue of the homothallic ascomycete Sordaria macrospora interacts
      with the MADS box protein MCM1 and is required for ascosporogenesis.
AB  - The MADS box protein MCM1 controls diverse developmental processes and is
      essential for fruiting body formation in the homothallic ascomycete Sordaria
      macrospora. MADS box proteins derive their regulatory specificity from a wide
      range of different protein interactions. We have recently shown that the S.
      macrospora MCM1 is able to interact with the alpha-domain mating-type protein
      SMTA-1. To further evaluate the functional roles of MCM1, we used the yeast two
      hybrid approach to identify MCM1-interacting proteins. From this screen, we
      isolated a protein with a putative N-terminal homeodomain and C-terminal C2/H2
      Zn2+ finger domains. The protein is a member of the highly conserved fungal STE12
      transcription factor family of proteins and was therefore termed STE12.
      Furthermore, we demonstrate by means of two-hybrid and far western analysis that
      in addition to MCM1, the S. macrospora STE12 protein is able to interact with the
      mating-type protein SMTA-1. Unlike the situation in the closely related
      heterothallic ascomycete Neurospora crassa, deletion (Delta) of the ste12 gene in
      S. macrospora neither affects vegetative growth nor fruiting body formation.
      However, ascus and ascospore development are highly impaired by the Deltaste12
      mutation. Our data provide another example of the functional divergence within
      the fungal STE12 transcription factor family.

PMID- 16999833
TI  - Type IV pili-dependent gliding motility in the Gram-positive pathogen Clostridium
      perfringens and other Clostridia.
AB  - Bacteria can swim in liquid media by flagellar rotation and can move on surfaces
      via gliding or twitching motility. One type of gliding motility involves the
      extension, attachment and retraction of type IV pili (TFP), which pull the
      bacterium towards the site of attachment. TFP-dependent gliding motility has been
      seen in many Gram-negative bacteria but not in Gram-positive bacteria. Recently,
      the genome sequences of three strains of Clostridium perfringens have been
      completed and we identified gene products involved in producing TFP in each
      strain. Here we show that C. perfringens produces TFP and moves with an unusual
      form of gliding motility involving groups of densely packed cells moving away
      from the edge of a colony in curvilinear flares. Mutations introduced into the
      pilT and pilC genes of C. perfringens abolished motility and surface localization
      of TFP. Genes encoding TFP are also found in the genomes of all nine Clostridium
      species sequenced thus far and we demonstrated that Clostridium beijerinckii can
      move via gliding motility. It has recently been proposed that the Clostridia are
      the oldest Eubacterial class and the ubiquity of TFP in this class suggests that
      a Clostridia-like ancestor possessed TFP, which evolved into the forms seen in
      many Gram-negative species.

PMID- 16999834
TI  - Loss of Hfq activates the sigmaE-dependent envelope stress response in Salmonella
      enterica.
AB  - Ubiquitous RNA-binding protein Hfq mediates the regulatory activity of many small
      RNAs (sRNAs) in bacteria. To identify potential targets for Hfq-mediated
      regulation in Salmonella, we searched for lacZ translational fusions whose
      activity varied in the presence or absence of Hfq. Fusions downregulated by Hfq
      were more common than fusions showing the opposite response. Surprisingly, in a
      subset of isolates from the major class, the higher activity in the absence of
      Hfq was due to transcriptional activation by the alternative sigma factor RpoE
      (sigmaE). Activation of the sigmaE regulon normally results from envelope stress
      conditions that elicit proteolytic cleavage of the anti-sigmaE factor RseA. Using
      an epitope tagged variant of RseA, we found that RseA is cleaved at an increased
      rate in a strain lacking Hfq. This cleavage was dependent on the DegS protease
      and could be completely prevented upon expressing the hfq gene from an inducible
      promoter. Thus, loss of Hfq function appears to affect envelope biogenesis in a
      way that mimics a stress condition and thereby induces the sigmaE response
      constitutively. In a RseA mutant, activation of the sigmaE response causes Hfq
      dependent downregulation of outer membrane protein (OMP) genes including lamB,
      ompA, ompC and ompF. For ompA, downregulation results in part from sigmaE
      dependent accumulation of MicA (SraD), a small RNA recently shown to downregulate
      ompA transcript levels in stationary phase. We show that the micA gene is under
      sigmaE control, and that DegS-mediated sigmaE release is required for the
      accumulation of MicA RNA upon entry into stationary phase. A similar mechanism
      involving additional, still unidentified, sRNAs, might underlie the growth phase
      dependent regulation of other OMP mRNAs.

PMID- 16999835
TI  - The Group B Streptococcus NADH oxidase Nox-2 is involved in fatty acid
      biosynthesis during aerobic growth and contributes to virulence.
AB  - Numerous Streptococcaceae produce an H2O-forming NADH oxidase, Nox-2, which has
      been generally implicated in aerobic survival. We examined the roles of Nox-2 in
      Group B Streptococcus (GBS), a leading agent of neonatal infections. While nox2
      inactivation caused an aerobic growth arrest, no improvement was seen by addition
      of antioxidants to cultures, suggesting that this defect was not due to
      accumulation of toxic oxygen species. Using several approaches, we show that the
      observed inability of the nox2 mutant to grow aerobically is mainly due to an
      underlying defect in fatty acid (FA) biosynthesis: (i) the nox2 aerobic growth
      defect is fully and rapidly complemented by adding oleic acid to culture medium,
      and (ii) direct assimilation of this unsaturated FA in both wild type (WT) and
      nox2 GBS membranes is demonstrated and correlated with mutant growth rescue. We
      propose that NAD+ depletion in the nox2 mutant results in reduced acetyl-CoA
      production, which perturbs FA biosynthesis and hence blocks growth in aerobiosis.
      The nox2 aerobic growth defect was also complemented when GBS respiration
      metabolism was activated by exogenous haem and menaquinone. The membrane NADH
      oxidase activity generated by the functional respiratory chain thus compensates
      the cytoplasmic NADH oxidase deficiency. The nox2 mutant was attenuated for
      virulence, as assessed in lung, intraperitoneal and intravenous murine infection
      models. As the nox2 defect seems only to affect aerobic growth of GBS, its
      reduced virulence supports the suggestion that aerobic conditions and NADH
      oxidase activities are relevant to the GBS infection process.

PMID- 16999836
TI  - Dual function of the germinal centre kinase Don3 during mitosis and cytokinesis
      in Ustilago maydis.
AB  - Septum formation is a crucial step of cytokinesis in fungi. In the basidiomycete
      Ustilago maydis, the germinal centre kinase Don3 triggers initiation of a
      secondary septum necessary for cell separation after cytokinesis. Here we show
      that oligomerization of Don3 via a putative coiled-coil domain is critical for
      secondary septum formation. Within the Don3 sequence we detected a characteristic
      C-terminal sequence motif (T-motif), which determines the subcellular
      localization of Don3 but is not required for regulation of cell separation. This
      motif defines a novel family of fungal protein kinases including Sid1p, an
      essential component of the septation initiation network (SIN) in
      Schizosaccharomyces pombe. Using the yeast two-hybrid system we isolated the Don3
      interacting protein Dip1, which is similar to S. pombe Cdc14p, another member of
      the SIN. Remarkably, deletion of dip1 did not interfere with cytokinesis in U.
      maydis, but both dip1 and don3 mutants were affected in nuclear envelope
      breakdown (NEBD) during mitosis. This phenotype has already been described for
      mutants, which lack the small GTPase Ras3, the U. maydis homologue of the SIN
      component Spg1p. We propose that the Don3 kinase exerts a dual function in the
      regulation of cell separation and NEBD.

PMID- 16999837
TI  - Topology and maturation of filamentous haemagglutinin suggest a new model for two
      partner secretion.
AB  - Two-partner secretion (TPS) is the most widely distributed secretion pathway
      known. These systems export large exoproteins through highly conserved channel
      forming beta-barrel proteins. Filamentous haemagglutinin (FHA), expressed by
      Bordetella species, is the prototypical TPS family member. Here we show that the
      C-terminus of mature FHA, as opposed to the N-terminus as previously proposed, is
      exposed on the cell surface and is required for mediating adherence to cultured
      epithelial cells. We show that the C-terminus of the FHA pro-protein (FhaB) is
      required for FHA function in vitro and in vivo and we show that cleavage of FhaB
      to form FHA is not the mechanism by which FHA is released from the cell. Based on
      these data, we propose a new model for TPS. This model provides an explanation
      for the energetics of export of globular protein domains across membranes in the
      absence of ATP and it suggests a new mechanism for the control of protein
      folding.

PMID- 16999839
TI  - Breakthrough pain in opioid-treated chronic non-malignant pain patients referred
      to a multidisciplinary pain centre: a preliminary study.
AB  - BACKGROUND: Breakthrough pain (BTP) has not formerly been discussed as such in
      chronic non-malignant pain patients referred to pain centres and clinics. The
      purpose of the study was to investigate the prevalence, characteristics and
      mechanisms of BTP in opioid-treated chronic non-malignant pain patients referred
      to a pain centre and to assess the short-term effects of pain treatment. METHODS:
      Patients were assessed at referral (T(0)) and after a treatment period of 3
      months (T(3)) using the visual analogue scale (VAS) of the brief pain inventory
      (BPI) within somatic nociceptive, neuropathic and/or visceral pain conditions,
      the mini mental state examination (MMSE) and the hospital anxiety and depression
      scale (HADS). The main treatment intervention from T(0) to T(3) was to convert
      short-acting oral opioids to long-acting oral opioids and to discontinue on
      demand and parenteral use of opioids. RESULTS: Thirty-three patients were
      assessed at T(0) and 27 at T(3). The prevalence of BTP declined significantly
      from T(0) (90%) to T(3) (70.4%). Worst, least, average and current pain
      intensities as well as duration of BTP were significantly reduced from T(0) to
      T(3.) The majority of BTPs were exacerbation of background pain assumed to be of
      the same pain mechanisms. High average pain intensity (BPI) was significantly
      associated with high scores for both anxiety and depression (HADS). CONCLUSION:
      BTP in chronic non-malignant pain patients seems to be surprisingly frequent and
      severe. Stabilizing the opioid regimen seems to reduce pain intensity in general
      as well as the intensity and duration of BTP. Average pain intensity was
      associated with anxiety and depression.

PMID- 16999840
TI  - Haemodynamic and metabolic effects of resuscitation with Ringer's ethyl pyruvate
      in the acute phase of porcine endotoxaemic shock.
AB  - BACKGROUND: Ethyl pyruvate has been shown to possess anti-inflammatory and free
      radical scavenging properties. However, the haemodynamic effects of ethyl
      pyruvate have not been studied in detail. We investigated the systemic, regional
      and microcirculatory haemodynamic and metabolic effects of resuscitation with
      Ringer's ethyl pyruvate solution (REPS) vs. Ringer's acetate (RA) in an acute
      model of porcine endotoxaemic shock. METHODS: Fourteen anaesthetized pigs
      received an infusion of endotoxin that was increased stepwise over 30 min to a
      rate of 2.5 microg/kg/h. After 60 min of endotoxaemia, the animals were
      resuscitated with either ethyl pyruvate 40 mg/kg, given as REPS, or the
      equivalent volume of RA, administered over 10 min. Thereafter, an infusion of
      either ethyl pyruvate 40 mg/kg/h, given as REPS, or the equivalent volume of RA,
      was started, and the maintenance fluid was reduced so that the total amount of
      fluid given was kept constant. The experiment was terminated after 300 min of
      endotoxaemia. RESULTS: Endotoxin infusion led to a hypodynamic state that was
      reversed by fluid resuscitation after 60 min. Progressive deterioration ensued
      and, after 300 min, all animals were again hypodynamic. No differences in
      response to treatment were found between the groups with regard to systemic
      haemodynamics, renal artery or portal vein flow or microcirculatory flow in the
      liver, kidney, ileal serosa or mucosa. Metabolic acidosis and increased arterial
      blood lactate developed in both groups, but, in the REPS group, the base excess
      was significantly lower from 150 min and the anion gap was significantly higher
      at 150 and 210 min. CONCLUSION: We could not demonstrate any difference between
      REPS and RA for resuscitation in this model of acute porcine endotoxaemic shock.

PMID- 16999841
TI  - Epidemiology of intensive care unit (ICU)-acquired infections in a 14-month
      prospective cohort study in a single mixed Scandinavian university hospital ICU.
AB  - BACKGROUND: Our aim was to evaluate the epidemiology of intensive care unit (ICU)
      acquired infections in a prospective cohort study. METHODS: Patients with longer
      than a 48-h stay in an adult mixed medical-surgical ICU in a tertiary level
      teaching hospital were included. The incidence (per cent) and incidence density
      (per 1000 patient days) of ICU-acquired infections and the device-associated
      infection rates per 1000 device days were analysed prospectively in a 14-month
      study. RESULTS: Eighty (23.9%) of 335 patients, whose ICU stay was longer than 48
      h, acquired a total of 107 infections (1.3 per patient) during their ICU stay,
      with an infection rate of 48 per 1000 patient days. The most common infections
      were ventilator-associated pneumonia (VAP) [33.8% (18.8 per 1000 respiratory
      days)], other lower respiratory tract infections (LRTIs) (20%) and sinusitis
      (13.8%). The rate of central catheter-related (CRI) or primary bloodstream
      infections was 6.3% (2.2 per 1000 central venous catheter days), and the rate of
      urinary tract infections was 1.3% (0.5 per 1000 urinary catheter days). The first
      ICU infection was observed in 58.8% (47/80) of cases within 6 days after
      admission. The median time from admission to the diagnosis of an ICU-acquired
      infection was 4 days (25th-75th percentiles, 4.0-6.0) for VAP, 6.0 days (4.5-7.0)
      for LRTIs and 9.5 days (6.5-13.0) for CRIs. CONCLUSIONS: The rates of urinary
      tract infections and bloodstream infections were lower than reported previously,
      differentiating our results from the classic pattern of ICU-acquired infections,
      with the exception of the predominance of VAP.

PMID- 16999843
TI  - Abstracts of the 14th Conference of the International Society of Differentiation,
      Innsbruck, Austria, October 7-11, 2006.

PMID- 16999842
TI  - Increase of plasma fibrinogen levels and variability with age in a sample of
      middle aged healthy men.
AB  - According to predictions from the current theoretical models for ageing the
      heterogeneity of the population is increasing with increasing age. Although the
      direct observation of such changes in humans is extremely difficult, supporting
      evidence should be identifiable in key biomarkers associated with health and
      mortality. Using data from the Northwick Park Heart Study II of 3052 healthy
      middle-aged men (mean 56 years of age, range 49-69 years), with 5 annual measures
      of CHD risk factors, ageing effects were tested for plasma fibrinogen,
      cholesterol and triglycerides. Fibrinogen levels increased with age (p < 0.0001),
      while cholesterol showed a decrease, and triglycerides did not show any change
      with age. There was a significant increase in the variance of fibrinogen with age
      (p < 0.0007) but not for cholesterol or triglycerides. The raising effect on
      fibrinogen levels associated with the A allele of the FIBB - 455G>A promoter
      variant also decreased with age (p = 0.005). The age-associated changes observed
      in the fibrinogen variability and the association of phenotype to genotype are
      discussed in light of the evolutionary theory, and their implications are
      considered.

PMID- 16999846
TI  - Characterisation of dic(9;20)(p11-13;q11) in childhood B-cell precursor acute
      lymphoblastic leukaemia by tiling resolution array-based comparative genomic
      hybridisation reveals clustered breakpoints at 9p13.2 and 20q11.2.
AB  - Although the dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in
      paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL), occurring in
      approximately 2% of the cases, its molecular genetic consequences have not been
      elucidated. In the present study, high-resolution genome-wide array-based
      comparative genomic hybridisation (array-CGH) and fluorescence in situ
      hybridisation (FISH) were used to characterise the 9p and 20q breakpoints (BPs)
      in seven childhood BCP ALLs with dic(9;20), which was shown to be unbalanced in
      all of them, resulting in loss of 9p13.2-pter. Five of the cases had loss of
      20q11.2-qter, whereas two displayed gain of 20cen-pter. All BPs on 9p clustered
      in a 1.5 Mb segment of the sub-band 9p13.2; in three of the cases, the 20q BPs
      mapped to three adjacent clones covering a distance of 350 kb at 20q11.2. Thus,
      the aberration should be designated dic(9;20)(p13.2;q11.2). One of the ALLs,
      shown to have a complex dic(9;20), was further investigated by FISH, revealing a
      rearrangement of the haemapoietic cell kinase isoform p61 (HCK) gene at 20q11.
      The disruption of HCK may result in a fusion gene or in loss of function.
      Unfortunately, lack of material precluded further analyses of HCK. Thus, it
      remains to be elucidated whether dic(9;20)(p13.2;q11.2) leads to a chimaeric gene
      or whether the functionally important outcome is loss of 9p and 20q material.

PMID- 16999847
TI  - The molecular basis of quantitative fibrinogen disorders.
AB  - Hereditary fibrinogen disorders include type I deficiencies (afibrinogenemia and
      hypofibrinogenemia, i.e. quantitative defects), with low or unmeasurable levels
      of immunoreactive protein; and type II deficiencies (dysfibrinogenemia and
      hypodysfibrinogenemia, i.e. qualitative defects), showing normal or altered
      antigen levels associated with reduced coagulant activity. While
      dysfibrinogenemias are in most cases autosomal dominant disorders, type I
      deficiencies are generally inherited as autosomal recessive traits. Patients
      affected by congenital afibrinogenemia or severe hypofibrinogenemia may
      experience bleeding manifestations varying from mild to severe. This review
      focuses on the genetic bases of type I fibrinogen deficiencies, which are
      invariantly represented by mutations within the three fibrinogen genes (FGA, FGB,
      and FGG) coding for the three polypeptide chains Aalpha, Bbeta, and gamma. From
      the inspection of the mutational spectrum of these disorders, some conclusions
      can be drawn: (i) genetic defects are scattered throughout the three fibrinogen
      genes, with only few sites appearing to represent relative mutational hot spots;
      (ii) several different types of genetic lesions and pathogenic mechanisms have
      been described in affected individuals (including gross deletions, point
      mutations causing premature termination codons, missense mutations affecting
      fibrinogen assembly/secretion, and uniparental isodisomy associated with a large
      deletion); (iii) the possibility to express recombinant fibrinogen mutants in
      eukaryotic cells is rapidly shedding light into the molecular mechanisms
      responsible for physiologic and pathologic properties of the molecule; (iv)
      though mutation analysis of the fibrinogen cluster does not yield precise
      information for predicting genotype/phenotype correlations, it still provides a
      valuable tool for diagnosis confirmation, identification of potential carriers,
      and prenatal diagnosis.

PMID- 16999848
TI  - Are placebo-controlled trials ethical in areas where current guidelines recommend
      therapy? Yes.

PMID- 16999849
TI  - New light on an old story: von Willebrand factor binding to collagen.

PMID- 16999850
TI  - Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von
      Willebrand disease: an international, multicenter study.
AB  - OBJECTIVES: We undertook an international, multicenter study to describe the
      clinical picture and to estimate the bleeding risk in a group of obligatory
      carriers of type 3 von Willebrand disease (VWD). PATIENTS AND METHODS: Obligatory
      carriers (OC) of type 3 VWD were identified by the presence of offspring with
      type 3 VWD or by being an offspring of a type 3 patient. Normal controls were age
      and sex-matched with the obligatory carriers. A physician-administered
      standardized questionnaire was used to evaluate hemorrhagic symptoms at
      presentation. A score system ranging from 0 (no symptom) to 3 (hospitalization,
      replacement therapy, blood transfusion) was used to quantitate bleeding
      manifestations. Odds ratios were computed for each symptom. RESULTS: Ten centers
      participated to the study, enrolling a total of 35 type 3 VWD families, with 70
      OC. A total of 215 normal controls and 42 OC for type 1 VWD were also included.
      About 40% of type 3 OC had at least one bleeding symptom compared to 23% of
      normal controls and 81.8% of type 1 OC (P < 0.0001 by chi-squared test), showing
      that type 3 OC clearly represent a distinct population from type 1 OC. The
      clinical situations associated with an increase of bleeding risk in type 3 OC
      were epistaxis [odds ratio 3.6; 90% confidence intervals (CI) 1.84-21.5],
      cutaneous bleeding (odds ratio 5.5; 90% CI 2.5-14.1) and postsurgical bleeding
      (odds ratio 16.3; 90% CI 4.5-59). The severity of bleeding score correlated with
      the degree of factor (F) VIII reduction in plasma. CONCLUSIONS: OC for type 3 VWD
      represent a distinctive population from type 1 OC. These patients, however,
      present with more frequent bleeding symptoms in comparison to normal controls,
      especially in case of significantly low FVIII. Desmopressin and/or tranexamic
      acid might be useful to prevent or treat bleeding in these cases.

PMID- 16999851
TI  - Family history and inherited thrombophilia.
AB  - BACKGROUND: It is a common belief that patients with venous thrombosis and a
      positive family history for venous thromboembolism (VTE) have an increased
      likelihood of having an inherited thrombophilic defect. METHODS: We analyzed the
      relation between family history, qualified with three different methods, and
      thrombophilic status in 314 patients with proven VTE. A positive family history
      (one or more first-degree relatives with VTE) and a strongly positive family
      history (two or more first-degree relatives with VTE). In 118 of the patients a
      third, more precise method was analyzed: the family history score, which compares
      the observed and the expected number of first-degree family members with VTE.
      RESULTS: Patients with a positive or strongly positive family history had a
      slightly increased chance of having inherited thrombophilia compared to those
      without a positive family history. For positive family history this was 42% vs.
      negative 32%, likelihood ratio 1.3 (95% confidence interval; CI 0.9-2.1) and for
      strongly positive family history this was 46% vs. negative 34%, likelihood ratio
      1.6 (95% CI 0.7-3.3). The family history score correlated with the chance of
      having inherited thrombophilia [OR 1.23 per score point (95% CI 1.01-1.48)].
      However, even with this method the chance of having inherited thrombophilia is
      lower than 50% in 97% of the cases. CONCLUSIONS: Family history of VTE is not a
      precise tool in clinical practice to identify patients with inherited
      thrombophilia among patients with VTE. The family history score is more precise,
      but probably only useful for research purposes and not for daily practice.

PMID- 16999852
TI  - Thrombin induces GPIb-IX-mediated fibrin binding to alphaIIbbeta3 in a
      reconstituted Chinese hamster ovary cell model.
AB  - BACKGROUND: The interaction of thrombin with platelet glycoprotein (GP) Ib-IX-V
      has been recently suggested to induce fibrin-dependent platelet aggregation
      associated with signaling events. The approaches used to avoid the protease
      activated receptor (PAR) thrombin receptors in platelets have provided
      controversial conclusions regarding the precise mechanism and molecules involved
      in the response. OBJECTIVES: In the present study, we developed a cellular model
      to investigate the functional consequences following the binding of thrombin to
      GPIb-IX. METHODS: We used Chinese hamster ovary (CHO) cells stably expressing
      human alpha(IIb)beta(3) and/or GPIb-IX complexes (CHO-alpha(IIb)beta(3)-IbIX
      cells) to analyze the effect of thrombin on the binding of polymerizing fibrin by
      using fluorescein isothiocyanate-fibrinogen as precursor. RESULTS: Thrombin
      induces, in a dose-dependent manner, the binding of polymerizing fibrin to CHO
      alpha(IIb)beta(3)-IbIX cells. This response is not observed in cells expressing
      only one of the receptors, and it can be blocked by monoclonal antibodies against
      alpha(IIb)beta(3) and GPIbalpha. We show that the reaction is not due to simple
      cell trapping by the fibrin clot, and provide data supporting a role of a
      signaling pathway in which the 14-3-3zeta adaptor and calcium-calmodulin
      dependent events are involved. CONCLUSIONS: The present data support a
      significant role of GPIb-IX and alpha(IIb)beta(3) receptors in an alternative
      fibrin-mediated pathway of platelet activation induced by thrombin.

PMID- 16999853
TI  - Plasma levels of the growth arrest-specific gene 6 product (Gas6) and
      antiplatelet drug responsiveness in healthy subjects.

PMID- 16999856
TI  - A comprehensive review of 46 exercise treatment studies in fibromyalgia (1988
      2005).
AB  - The purpose of this review was to: (1) locate all exercise treatment studies of
      fibromyalgia (FM) patients from 1988 through 2005, (2) present in tabular format
      the key details of each study and (3) to provide a summary and evaluation of each
      study for exercise and health outcomes researchers. Exercise intervention studies
      in FM were retrieved through Cochrane Collaboration Reviews and key word searches
      of the medical literature, conference proceedings and bibliographies. Studies
      were reviewed for inclusion using a standardized process. A table summarizing
      subject characteristics, exercise mode, timing, duration, frequency, intensity,
      attrition and outcome variables was developed. Results, conclusions and comments
      were made for each study. Forty-six exercise treatment studies were found with a
      total of 3035 subjects. The strongest evidence was in support of aerobic exercise
      a treatment prescription for fitness and symptom and improvement. In general, the
      greatest effect and lowest attrition occurred in exercise programs that were of
      lower intensity than those of higher intensity. Exercise is a crucial part of
      treatment for people with FM. Increased health and fitness, along with symptom
      reduction, can be expected with exercise that is of appropriate intensity, self
      modified, and symptom-limited. Exercise and health outcomes researchers are
      encouraged to use the extant literature to develop effective health enhancing
      programs for people with FM and to target research to as yet understudied FM
      subpopulations, such as children, men, older adults, ethnic minorities and those
      with common comorbidities of osteoarthritis and obesity.

PMID- 16999857
TI  - ABCB1 genotypes and haplotypes in patients with dementia and age-matched non
      demented control patients.
AB  - Amyloid beta is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump
      at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene,
      encoding for P-gp, is highly polymorphic and this may result in a changed
      function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's
      disease. This study investigates to what extent ABCB1 Single Nucleotide
      Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon
      26) and inferred haplotypes exist in an elderly population and if these SNPs and
      haplotypes differ between patients with dementia and age-matched non-demented
      control patients. ABCB1 genotype, allele and haplotype frequencies were neither
      significantly different between patients with dementia and age-matched controls,
      nor between subgroups of different types of dementia nor age-matched controls.
      This study shows ABCB1 genotype frequencies to be comparable with described
      younger populations. To our knowledge this is the first study on ABCB1 genotypes
      in dementia. ABCB1 genotypes are presently not useful as a biomarker for
      dementia, as they were not significantly different between demented patients and
      age-matched control subjects.

PMID- 16999858
TI  - Four cycles of paclitaxel and carboplatin as adjuvant treatment in early-stage
      ovarian cancer: a six-year experience of the Hellenic Cooperative Oncology Group.
AB  - BACKGROUND: Surgery can cure a significant percentage of ovarian carcinoma
      confined to the pelvis. Nevertheless, there is still a 10-50% recurrence rate. We
      administered paclitaxel/carboplatin as adjuvant treatment in early-stage ovarian
      carcinoma. METHODS: Patients with stages Ia or Ib, Grade 2 or 3 and Ic to IIb
      (any grade) were included. Patients were treated with 4 cycles of Paclitaxel 175
      mg/m2 and Carboplatin [area under the curve (AUC) 6 (Calvert Formula)] every 3
      weeks. RESULTS: Sixty-nine patients with no residual disease following
      cytoreductive surgery and minimal or modified surgical staging were included in
      this analysis. Grade 3 or 4 neutropenia occurred in 29.9% of patients, while
      neutropenic fever was reported in 4.5%. Neurotoxicity (all Grade 1 or 2) was
      reported in 50% of cases. Median follow-up was 62 months. 5-year overall survival
      (OS) and relapse-free survival (RFS) were: 87% (95% confidence intervals [CI]: 78
      96) and 79% (95% CI: 69-89), respectively. Significantly fewer patients with
      stages Ic-IIb and tumor grade 2 or 3 achieved a 5-year RFS than patients with
      only one of these two factors (73% vs 92%, p = 0.03). CONCLUSION:
      Paclitaxel/Carboplatin chemotherapy is a safe and effective adjuvant treatment in
      early-stage ovarian carcinoma. Patients with stages Ic-IIb and tumor grade 2 or 3
      may benefit from more extensive treatment.

PMID- 16999859
TI  - Deep penetrating nevus: a case report and brief literature review.
AB  - BACKGROUND: Deep penetrating nevus (DPN) is a distinct variant of melanocytic
      nevus and remains a histopathologic challenge to pathologists because of its
      resemblance to blue nevus, malignant melanoma, pigmented Spitz nevus, and
      congenital melanocytic nevus. It often goes unrecognized due to its relative
      rarity. CASE PRESENTATION: Here we report a case of DPN of the left anterior leg
      in a 51-year old female. A brief review of the literature shows that these
      lesions have a distinct growth pattern and cellular morphology that can
      differentiate these lesions from other entities including malignant melanoma.
      CONCLUSION: It is important to recognize these features because DPN carries a
      better prognosis than malignant melanoma.

PMID- 16999860
TI  - Fast calculation of the quartet distance between trees of arbitrary degrees.
AB  - BACKGROUND: A number of algorithms have been developed for calculating the
      quartet distance between two evolutionary trees on the same set of species. The
      quartet distance is the number of quartets - sub-trees induced by four leaves -
      that differs between the trees. Mostly, these algorithms are restricted to work
      on binary trees, but recently we have developed algorithms that work on trees of
      arbitrary degree. RESULTS: We present a fast algorithm for computing the quartet
      distance between trees of arbitrary degree. Given input trees T and T', the
      algorithm runs in time O(n + /V/./V'/ min{id, id'}) and space O(n + /V/./V'/),
      where n is the number of leaves in the two trees, V and V are the non-leaf nodes
      in T and T', respectively, and id and id' are the maximal number of non-leaf
      nodes adjacent to a non-leaf node in T and T', respectively. The fastest
      algorithms previously published for arbitrary degree trees run in O(n3)
      (independent of the degree of the tree) and O(/V/./V'/.id.id'), respectively. We
      experimentally compare the algorithm with existing algorithms for computing the
      quartet distance for general trees. CONCLUSION: We present a new algorithm for
      computing the quartet distance between two trees of arbitrary degree. The new
      algorithm improves the asymptotic running time for computing the quartet
      distance, compared to previous methods, and experimental results indicate that
      the new method also performs significantly better in practice.

PMID- 16999861
TI  - Correlates of HCV seropositivity among familial contacts of HCV positive
      patients.
AB  - BACKGROUND: Determinants of intrafamilial HCV transmission are still being
      debated. The aim of this study is to investigate the correlates of HCV
      seropositivity among familial contacts of HCV positive patients in Italy.
      METHODS: A cross-sectional study was conducted with 175 HCV positive patients
      (index cases), recruited from Policlinico Gemelli in Rome as well as other
      hospitals in Central Italy between 1995 and 2000 (40% female, mean age 57 +/-
      15.2 years), and 259 familial contacts. Differences in proportions of qualitative
      variables were tested with non-parametric tests (chi2, Yates correction, Fisher
      exact test), and a p value < 0.05 was considered significant. A multivariate
      analysis was conducted using logistic regression in order to verify which
      variables statistically have an influence on HCV positivity in contact
      individuals. RESULTS: Seropositivity for HCV was found in 8.9% of the contacts.
      From the univariate analysis, risk factors significantly associated to HCV
      positivity in the contacts were: intravenous drug addiction (p = 0.004) and
      intercourse with drug addicts (p = 0.005). The only variables associated
      significantly and independently to HCV seropositivity in patients' contacts were
      intercourse with drug addicts (OR = 19.28; 95% CI: 2.01 - 184.94), the retirement
      status from work (OR = 3.76; 95% CI: 1.17 - 11.98), the time of the relationship
      (OR = 1.06; 95% CI: 1.00 - 1.11) and tattoos (OR = 7.68; 95% CI: 1.00 - 60.20).
      CONCLUSION: The present study confirms that having intercourse with a drug addict
      is the most significant risk factor for intrafamilial HCV transmission. The
      association with retirement status from work could be related to both a long-term
      relationship with an index case and past exposure to common risk factors.

PMID- 16999862
TI  - The screening power of methylenetetrahydrofolate reductase C677T polymorphism
      versus plasma homocysteine concentration in patients with stenosis of the
      internal carotid artery.
AB  - BACKGROUND: Hyperhomocysteinemia is an important and independent risk factor for
      vascular disease. About 35% of patients with stroke and 47% of patients with
      peripheral arterial disease have elevated plasma homocysteine (HCY)
      concentrations. The relationship between plasma HCY and the
      methylentetrahydrofolate reductase (MTHFR) C677T polymorphism is still unclear,
      especially in regard to screening/diagnostic power. METHODS: This case-control
      study was performed on 96 patients, who underwent surgery due to asymptomatic or
      symptomatic high grade stenosis of the internal carotid artery (ICA), and 96
      healthy age and sex-matched, controls. Plasma HCY concentration was determined
      using a commercial kit for fully automated analysis (AxSYM, Abbott). The C677T
      polymorphism of the MTHFR-gene was assessed by PCR. RESULTS: The mean plasma HCY
      concentration was significantly higher in the group with stenosis of ICA compared
      to the controls, 12.43 +/- 6.96 microM and 10.16 +/- 3.16 microM, respectively,
      (p < 0.05). An HCY plasma concentration of 1.5 SD above the mean value of the
      control group, was defined as cut-off for a pathological versus physiological
      plasma concentration. The sensitivity and specificity of HCY was 0.27 and 0.94,
      respectively. The positive predictive value was 0.82. There was no significant
      difference in the frequency of the MTHFR 677 CT and TT genotype between patients
      and controls (47% vs. 47% and 8.3% vs. 11.4%, respectively). Carriers of the T
      allele (CT and TT genotypes) have significantly higher plasma HCY concentrations
      than CC patients, 14.1 +/- 7.6 microM and 10.29 +/- 5.2 microM, respectively, p <
      0.05. Sensitivity and specificity of the MTHFR C677T polymorphism (T-allele) were
      0.56 and 0.40, respectively. The positive predictive value was 0.48. There was no
      significant difference in plasma HCY or genotype frequency of the MTHFR C677T
      polymorphism between asymptomatic and symptomatic patients. CONCLUSION: Our study
      shows that in a population with a given pretest disease probability of 50%, the
      determination of plasma HCY concentration, with a positive predictive value of
      0.82, is more suitable for screening of patients at risk than analysis of the
      MTHFR C677T polymorphism.

PMID- 16999863
TI  - The role of body mass index and diabetes in the development of acute organ
      failure and subsequent mortality in an observational cohort.
AB  - INTRODUCTION: Several studies have shown a correlation between body mass index
      (BMI) and both the development of critical illness and adverse outcomes in
      critically ill patients. The goal of our study was to examine this relationship
      prospectively with particular attention to the influence of concomitant diabetes
      mellitus (DM). METHODS: We analyzed data from 15,408 participants in the
      Atherosclerosis Risk in Communities (ARIC) study for this analysis. BMI and the
      presence of DM were defined at baseline. We defined 'acute organ failure' as
      those subjects who met a standard definition with diagnostic codes abstracted
      from hospitalization records. Outcomes assessed included the following: risk of
      the development of acute organ failure within three years of the baseline
      examination; in-hospital death while ill with acute organ failure; and death at
      three years among all subjects and among those with acute organ failure. RESULTS:
      At baseline, participants with a BMI of at least 30 were more likely than those
      in lower BMI categories to have DM (22.4% versus 7.9%, p < 0.01). Overall, BMI
      was not a significant predictor of developing acute organ failure. The risk for
      developing acute organ failure was increased among subjects with DM in comparison
      with those without DM (2.4% versus 0.7%, p < 0.01). Among subjects with organ
      failure, both in-hospital mortality (46.5% versus 12.2%, p < 0.01) and 3-year
      mortality (51.2% versus 21.1%, p < 0.01) was higher in subjects with DM.
      CONCLUSION: Our findings suggest that obesity by itself is not a significant
      predictor of either acute organ failure or death during or after acute organ
      failure in this cohort. However, the presence of DM, which is related to obesity,
      is a strong predictor of both acute organ failure and death after acute organ
      failure.

PMID- 16999864
TI  - Individual freedom versus collective responsibility: an ethicist's perspective.
AB  - Philosophical theories of collective action have produced a number of alternative
      accounts of the rationality and morality of self-interest and altruism. These
      have obvious applications to communicable disease control, the avoidance of
      antibiotic resistance, the responsibility of healthcare professionals to patients
      with serious communicable diseases, and the sharing of personal data in
      epidemiological research.

PMID- 16999865
TI  - Psycho-social and environmental correlates of location-specific physical activity
      among 9- and 15- year-old Norwegian boys and girls: the European Youth Heart
      Study.
AB  - OBJECTIVE: Little is known about the existence of independent location- or
      context specific forms of physical activity. This study sought to identify
      location-specific forms of physical activity in a sample of 9 and 15 years-olds
      Norwegian boys and girls, and examined their associations to psycho-social and
      environmental factors. METHODS: A cross-sectional study of 9 and 15-year-olds (N
      = 760; 379 boys and 381 girls) was conducted in which participants responded to a
      computer-based questionnaire (PEACH) tapping potentially location specific forms
      of physical activity as well as psycho-social and environmental correlates.
      RESULTS: Exploratory factor analysis indicated that the nine and fifteen year
      olds self-reported their physical activity as located in three separate and
      specific contexts: a) school commuting, b) informal games play at school and c)
      organized sport, structured exercise and games play in leisure time. Dependent of
      location, psycho-social and environmental correlates explained between 15 and 55
      percent of the variance in physical activity. The impact of peer support,
      enjoyment and perceived competence in physical activity generalized across the
      three locations. Enjoyment of physical education classes, parental support and
      teacher support, in contrast, confined to particular location-specific forms of
      physical activity. Generally, behavioural beliefs and environmental factors
      represented marginal correlates of all location-specific forms of activity.
      CONCLUSION: Young peoples' physical activity was identified as taking place in
      multiply genuine locations, and the psychosocial correlates of their physical
      activity seem to some extent to be location specific. Results may inform
      intervention efforts suggesting that targeting specific sets of psycho-social
      factors may prove efficient across physical activity locations, gender and age
      groups. Others, in contrast may prove effective in facilitating location specific
      physical activity, in which age may come to moderate the efficiency of
      intervention efforts.

PMID- 16999866
TI  - Prevention of an additional surgery for regional lymphadenectomy in melanoma:
      rapid intraoperative immunostaining of sentinel lymph node imprint smears.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy is performed at many institutions
      and is considered a standard of care in the management of cutaneous melanoma. The
      discriminatory immunostaining pattern with the 'MCW Melanoma Cocktail' (a mixture
      of MART-1 {1:500}, Melan- A {1:100}, and Tyrosinase {1:50} monoclonal antibodies)
      allows intraoperative immunocytochemical evaluation of imprint smears of SLNs for
      melanoma metastases. Cohesive cells of benign capsular melanocytic nevi that were
      also immunoreactive with the cocktail do not exfoliate easily for imprint smear
      detection. METHODS: We prospectively evaluated 73 lymph nodes (70 SLN & 3 non
      SLN) from 41 cases (mean 1.8, 1 to 4 SLNs/case) of cutaneous melanoma using a
      rapid 17-minute immunostaining previously published protocol. The results were
      compared with permanent sections also immunostained with 'the cocktail'. RESULTS:
      19.5%, 8/41 cases (12%, 9/73 lymph nodes) were positive for melanoma metastases
      on permanent sections immunostained with the 'MCW melanoma cocktail'. Melanoma
      metastases in 87.5% (7/8) of these cases were also detected in rapidly
      immunostained imprint smears, with 100% specificity and 90% sensitivity. None of
      the 7 SLNs from 7 cases with capsular nevi showed false positive results.
      CONCLUSION: Melanoma metastases could be detected in imprint smears immunostained
      with 'MCW Melanoma Cocktail' utilizing a rapid intraoperative protocol. The
      cohesive cells of the capsular nevi do not readily exfoliate and do not lead to
      false positive interpretation. In a majority of positive cases, a regional
      lymphadenectomy could have been completed during the same surgery for SLN biopsy
      and wide excision of primary melanoma site, potentially eliminating the need for
      an additional surgery.

PMID- 16999867
TI  - Possible involvement of integrin-mediated signalling in oocyte activation:
      evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and
      cortical granule exocytosis in mouse oocytes.
AB  - BACKGROUND: Mammalian sperm-oocyte interaction at fertilization involves several
      combined interactions between integrins on the oocyte and integrin ligands
      (disintegrins) on the sperm. Recent research has indicated the ability of
      peptides containing the RGD sequence that characterized several sperm
      disintegrins, to induce intracellular Ca2+ transients and to initiate
      parthenogenetic development in amphibian and bovine oocytes. In the present
      study, we investigate the hypothesis that an integrin-associated signalling may
      participate in oocyte activation signalling by determining the ability of a
      cyclic RGD-containing peptide to stimulate the activation of protein kinase C
      (PKC) and the exocytosis of cortical granules in mouse oocytes. METHODS: An In
      Vitro-Fertilization assay (IVF) was carried in order to test the condition under
      which a peptide containing the RGD sequence, cyclo(Arg-Gly-Asp-D-Phe-Val), was
      able to inhibit sperm fusion with zona-free mouse oocytes at metaphase II stage.
      PKC activity was determined by means of an assay based on the ability of cell
      lysates to phosphorylate MARKS peptide, a specific PKC substrate. Loss of
      cortical granules was evaluated by measuring density in the oocyte cortex of
      cortical granules stained with LCA-biotin/Texas red-streptavidin. In all the
      experiments, effects of a control peptide containing a non RGD sequence,
      cyclo(Arg-Ala-Asp-D-Phe-Val), were evaluated. RESULTS: The IVF assay revealed
      that the fusion rate declined significantly when insemination was carried out in
      the presence of cyclic RGD peptide at concentrations > or = 250 microM (P < 0.05,
      Student-Newman-Keuls Method). When the peptide was applied to the oocytes at
      these concentrations, a dose-dependent increase of PKC activity was observed, in
      association with a loss of cortical granules ranging from 38+/-2.5 % to 52+/-5.4
      %. Evaluation of meiotic status revealed that cyclic RGD peptide was ineffective
      in inducing meiosis resumption under conditions used in the present study.
      CONCLUSION: The presents results provide evidence that a cyclic RGD peptide
      highly effective in inhibiting sperm-oocyte interaction stimulates in mouse
      oocytes the activation of PKC and the exocytosis of cortical granules. These data
      support the view that RGD-binding receptors may function as signalling receptors
      giving rise integrated signalling not sufficient for a full oocyte activation
      response. This study may contribute to the understanding of possible negative
      effects of skipping gamete interaction in IVF techniques.

PMID- 16999868
TI  - Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of
      heterosexual Italian HIV-1 exposed uninfected individuals.
AB  - Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1
      seronegative (exposed seronegative, ESN). The mechanisms underlying this
      resistance remain still unclear, although a multifactorial pathogenesis can be
      hypothesised. Although several genetic factors have been related to HIV-1
      resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion,
      i.e. CCR5-Delta32 allele) is presently considered the most relevant one. In the
      present study we analysed the genotype at CCR5 locus of 30 Italian ESN
      individuals (case group) who referred multiple unprotected heterosexual
      intercourse with HIV-1 seropositive partner(s), for at least two years. One
      hundred and twenty HIV-1 infected patients and 120 individuals representative of
      the general population were included as control groups. Twenty percent of ESN
      individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1
      seropositive and 10% of individuals from the general population, respectively.
      None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence
      analysis of the entire open reading frame of CCR5 was performed in all ESN
      subjects and no polymorphisms or mutations were identified. Moreover, we
      determined the distribution of C77G variant in CD45 gene, which has been
      previously related to HIV-1 infection susceptibility. The frequency of the C77G
      variant showed no significant difference between ESN subjects and the two control
      groups. In conclusion, our data show a significantly higher frequency of CCR5
      Delta 32 heterozygous genotype (p = 0.04) among the Italian heterosexual ESN
      individuals compared to HIV-1 seropositive patients, suggesting a partial
      protective role of CCR5-Delta 32 heterozygosity in this cohort.

PMID- 16999869
TI  - Prevention for those who have freedom of choice--or among the choice-disabled:
      confronting equity in the AIDS epidemic.
AB  - With the exception of post-exposure prophylaxis for reported rape, no preventive
      strategy addresses the choice disabled - those who might like to benefit from
      AIDS prevention but who are unable to do so because they do not have the power to
      make and to act on prevention decisions. In southern African countries, where one
      in every three has been forced to have sex by the age of 18 years, a very large
      proportion of the population is choice disabled. This group is at higher risk of
      HIV infection and unable to respond to AIDS prevention programmes; they represent
      a reservoir of infection. Reduction of sexual violence would probably decrease
      HIV transmission directly, but also indirectly as more people can respond to
      existing AIDS prevention programmes.

PMID- 16999870
TI  - Alternative protocol to initiate high-frequency oscillatory ventilation: an
      experimental study.
AB  - INTRODUCTION: The objective was to study the effects of a novel lung volume
      optimization procedure (LVOP) using high-frequency oscillatory ventilation (HFOV)
      upon gas exchange, the transpulmonary pressure (TPP), and hemodynamics in a
      porcine model of surfactant depletion. METHODS: With institutional review board
      approval, the hemodynamics, blood gas analysis, TPP, and pulmonary shunt fraction
      were obtained in six anesthetized pigs before and after saline lung lavage.
      Measurements were acquired during pressure-controlled ventilation (PCV) prior to
      and after lung damage, and during a LVOP with HFOV. The LVOP comprised a
      recruitment maneuver with a continuous distending pressure (CDP) of 45 mbar for
      2.5 minutes, and a stepwise decrease of the CDP (5 mbar every 5 minute) from 45
      to 20 mbar. The TPP level was identified during the decrease in CDP, which
      assured a change of the PaO2/FIO2 ratio < 25% compared with maximum lung
      recruitment at CDP of 45 mbar (CDP45). Data are presented as the median (25th
      75th percentile); differences between measurements are determined by Friedman
      repeated-measures analysis on ranks and multiple comparisons (Tukey's test). The
      level of significance was set at P < 0.05. RESULTS: The PaO2/FiO2 ratio increased
      from 99.1 (56.2-128) Torr at PCV post-lavage to 621 (619.4-660.3) Torr at CDP45
      (CDP45) (P < 0.031). The pulmonary shunt fraction decreased from 51.8% (49-55%)
      at PCV post-lavage to 1.03% (0.4-3%) at CDP45 (P < 0.05). The cardiac output and
      stroke volume decreased at CDP45 (P < 0.05) compared with PCV, whereas the heart
      rate, mean arterial pressure, and intrathoracic blood volume remained unchanged.
      A TPP of 25.5 (17-32) mbar was required to preserve a difference in PaO2/FIO2
      ratio < 25% related to CDP45; this TPP was achieved at a CDP of 35 (25-40) mbar.
      CONCLUSION: This HFOV protocol is easy to perform, and allows a fast
      determination of an adequate TPP level that preserves oxygenation. Systemic
      hemodynamics, as a measure of safety, showed no relevant deterioration throughout
      the procedure.

PMID- 16999871
TI  - Knowledge transfer & exchange through social networks: building foundations for a
      community of practice within tobacco control.
AB  - BACKGROUND: Health services and population health innovations advance when
      knowledge transfer and exchange (KTE) occurs among researchers, practitioners,
      policy-makers and consumers using high-quality evidence. However, few KTE models
      have been evaluated in practice. Communities of practice (CoP) - voluntary, self
      organizing, and focused groups of individuals and organizations - may provide one
      option. This paper outlines an approach to lay the foundation for a CoP within
      the area of Web-assisted tobacco interventions (WATI). The objectives of the
      study were to provide a data-driven foundation to inform decisions about
      organizing a CoP within the geographically diverse, multi-disciplinary WATI group
      using evaluation and social network methodologies. METHODS: A single-group design
      was employed using a survey of expectations, knowledge, and interpersonal WATI
      related relationships administered prior to a meeting of the WATI group followed
      by a 3-week post-meeting Web survey to assess short-term impact on learning and
      networking outcomes. RESULTS: Twenty-three of 27 WATI attendees (85%) from
      diverse disciplinary and practice backgrounds completed the baseline survey, with
      21 (91%) of those participants completing the three-week follow-up. Participants
      had modest expectations of the meeting at baseline. A social network map produced
      from the data illustrated a centralized, yet sparse network comprising of
      interdisciplinary teams with little trans-sectoral collaboration. Three-week
      follow-up survey results showed that participants had made new network
      connections and had actively engaged in KTE activities with WATI members outside
      their original network. CONCLUSION: Data illustrating both the shape and size of
      the WATI network as well as member's interests and commitment to KTE, when shared
      and used to frame action steps, can positively influence the motivation to
      collaborate and create communities of practice. Guiding KTE planning through
      blending data and theory can create more informed transdisciplinary and trans
      sectoral collaboration environments.

PMID- 16999872
TI  - Role of the unique N-terminal domain of CtBP2 in determining the subcellular
      localisation of CtBP family proteins.
AB  - BACKGROUND: CtBP1 and CtBP2 are transcriptional co-repressors that modulate the
      activity of a large number of transcriptional repressors via the recruitment of
      chromatin modifiers. Many CtBP-regulated proteins are involved in pathways
      associated with tumorigenesis, including TGF-beta and Wnt signalling pathways and
      cell cycle regulators such as RB/p130 and HDM2, as well as adenovirus E1A. CtBP1
      and CtBP2 are highly similar proteins, although evidence is emerging that their
      activity can be differentially regulated, particularly through the control of
      their subcellular localisation. CtBP2s from diverse species contain a unique N
      terminus, absent in CtBP1 that plays a key role in controlling the nuclear
      cytoplasmic distribution of the protein. RESULTS: Here we show that amino acids
      (a.a.) 4-14 of CtBP2 direct CtBP2 into an almost exclusively nuclear distribution
      in cell lines of diverse origins. Whilst this sequence contains similarity to
      known nuclear localisation motifs, it cannot drive nuclear localisation of a
      heterologous protein, but rather has been shown to function as a p300
      acetyltransferase-dependent nuclear retention sequence. Here we define the region
      of CtBP2 required to co-operate with a.a. 4-14 to promote CtBP2 nuclear
      accumulation as being within a.a. 1-119. In addition, we show that a.a. 120-445
      of CtBP2 can also promote CtBP2 nuclear accumulation, independently of a.a. 4-14.
      Finally, CtBP1 and CtBP2 can form heterodimers, and we show that the interaction
      with CtBP2 is one mechanism whereby CtBP1 can be recruited to the nucleus.
      CONCLUSION: Together, these findings represent key distinctions in the regulation
      of the functions of CtBP family members that may have important implications as
      to their roles in development, and cell differentiation and survival.

PMID- 16999873
TI  - Mutual obligation, shared responsibility agreements & indigenous health strategy.
AB  - Since 2004 the Howard Coalition government has implemented a new policy framework
      and administrative arrangements as part of its program of reform in Indigenous
      affairs. In this paper I will describe both the parameters of this reform program
      and review the processes established to support the implementation of national
      Indigenous health strategy. In particular, I will consider both the shift from a
      policy framework based on 'self-determination' to one based on 'mutual
      obligation', and the implementation of Shared Responsibility Agreements (SRAs)
      that are based on the latter principle. I will use the example of the Mulan SRA
      to illustrate the difficulties in articulating the 'new arrangements' with
      current approaches to Indigenous health planning and strategy implementation. I
      conclude that 'new arrangements' pose a number of problems for Indigenous health
      planning and strategy that need to be addressed.

PMID- 16999874
TI  - Understanding environmental influences on nutrition and physical activity
      behaviors: where should we look and what should we count?
AB  - Research interest in the influence of environmental factors on nutrition and
      physical activity behaviors has surged internationally in recent years. This is
      evident from a rapidly expanding literature and facilitated by advances in
      methodological and analytical approaches to assessing multiple levels of
      influence on health behaviors. However, a number of conceptual challenges
      complicate research endeavours in this field. The purpose of this paper is to
      provide a 'state of the science' overview of evidence regarding environmental
      influences on nutrition and physical activity behaviors. We focus particularly on
      a number of key conceptual and methodological issues, including: a consideration
      of how the environment is defined; the selection and operationalization of
      environmental exposures; and the importance of integrating existing understanding
      of individual influences on behavior with the emerging data on the role of the
      environment. We draw on examples from the published literature including our own
      research studies to illustrate these issues. We conclude by proposing a research
      agenda to progress understanding of the influences of the environment on
      population nutrition and physical activity behaviors.

PMID- 16999875
TI  - Understanding the dynamics of Ebola epidemics.
AB  - Ebola is a highly lethal virus, which has caused at least 14 confirmed outbreaks
      in Africa between 1976 and 2006. Using data from two epidemics [in Democratic
      Republic of Congo (DRC) in 1995 and in Uganda in 2000], we built a mathematical
      model for the spread of Ebola haemorrhagic fever epidemics taking into account
      transmission in different epidemiological settings. We estimated the basic
      reproduction number (R0) to be 2.7 (95% CI 1.9-2.8) for the 1995 epidemic in DRC,
      and 2.7 (95% CI 2.5-4.1) for the 2000 epidemic in Uganda. For each epidemic, we
      quantified transmission in different settings (illness in the community,
      hospitalization, and traditional burial) and simulated various epidemic scenarios
      to explore the impact of control interventions on a potential epidemic. A key
      parameter was the rapid institution of control measures. For both epidemic
      profiles identified, increasing hospitalization rate reduced the predicted
      epidemic size.

PMID- 16999876
TI  - Short report: analysis of clonal relationship among Shigella sonnei isolates
      circulating in Argentina.
AB  - Thirty-five isolates of Shigella sonnei from patients with diarrhoea in three
      geographic regions of Argentina were examined for genetic diversity by pulsed
      field gel electrophoresis (PFGE) and plasmid profile. PFGE of XbaI and BlnI DNA
      digests confirmed the occurrence of outbreaks in two regions caused by two
      separate predominant clones of S. sonnei. The third region was characterized by
      three circulating clones, one of which was possibly associated with an outbreak.
      Similar plasmids were found in distinct clones and in one outbreak clone five
      different plasmid profiles were identified. Antimicrobial resistance of the
      isolates varied from fully susceptible to the agents tested, to resistance to
      cotrimoxazole, ampicillin and ciprofloxacin. Antibiotic resistance did not
      correlate with plasmid content. This information will form the basis for active
      surveillance of shigellosis in Argentina and elsewhere in the region through the
      PulseNet International Network.

PMID- 16999877
TI  - Hepatitis A virus infection in people of South Asian origin in England and Wales:
      analysis of laboratory reports between 1992 and 2004.
AB  - The aim of the study was to determine whether rates of hepatitis A infection are
      higher in people of South Asian origin compared to the general population, to
      look for evidence of spread to the general population, and to identify ways to
      improve preventive strategies. Routine laboratory reports of hepatitis A
      infection in England and Wales in 1992-2004 were analysed. Study participants
      were patients with confirmed hepatitis A infection reported to the Health
      Protection Agency by the diagnosing laboratory. Nam Pehchan software was used to
      identify patients of South Asian ethnicity. Main outcome measures were comparison
      of incidence of hepatitis A in South Asian and non-South Asian groups, by age and
      region. Rates of infection were significantly higher in the South Asian group
      compared to the non-South Asian group (rate ratio 2.68, 95% confidence interval
      2.07-3.47). Patients in the South Asian group had a younger age distribution.
      Travel was an important risk factor with 85% of those of South Asian origin
      acquiring their infection abroad, most frequently in the Indian subcontinent,
      compared to less than one third of those in other groups. Health-care
      professionals should ensure that all travellers to high-risk countries are
      protected by hepatitis A vaccination. Targeted information campaigns may be
      indicated in regions of the United Kingdom for people in South Asian minority
      ethnic groups.

PMID- 16999878
TI  - Obsessive-compulsive disorder, tics and anxiety in 6-year-old twins.
AB  - BACKGROUND: Previous reports of genetic influences on obsessive-compulsive
      disorder (OCD) symptoms have suggested moderate heritability. Family history
      studies of co-morbidity have found familial aggregation with tics, especially for
      early-onset OCD, and familial aggregation with anxiety disorders. METHOD:
      Heritability of OCD and familial aggregation of OCD, tics and anxiety disorders
      were investigated in a community sample of 6-year-old twins using a two-phase
      design in which 4662 twin pairs were sampled and 854 pairs were assessed in the
      second phase by maternal-informant diagnostic interview using DSM-IV criteria.
      RESULTS: In the multivariate model combined additive genetic and common
      environmental effects were estimated as 47% for sub-threshold OCD, and the model
      was unable to distinguish these sources of familial aggregation. There were
      strong familial aggregations between sub-threshold OCD and tics and between sub
      threshold OCD and other anxiety disorders (80% and 97% respectively), although
      again specific sources could not be distinguished. CONCLUSIONS: The findings are
      consistent with the hypothesis of a tic-related early-onset OCD phenotype, but
      also with the hypothesis of an anxiety-related early-onset OCD phenotype.

PMID- 16999879
TI  - The use of complementary and alternative medicine in the general population:
      results from a longitudinal community study.
AB  - BACKGROUND: Many patients with psychological or physical problems are interested
      in non-medical approaches. The reasons for the growing popularity of
      complementary and alternative medicine (CAM) are not well understood considering
      that evidence of the effectiveness of conventional therapies is greater than ever
      before. We have examined data from the Zurich Study to determine trends and
      predictors of CAM use in Switzerland. METHOD: The Zurich Study is a longitudinal
      community study that was started in 1979 with a sample of 591 participants born
      in 1958 and 1959. In 1999, the last of six interview waves with face-to-face
      interviews was conducted. CAM use was analyzed with data from interviews in 1993
      and 1999. Polytomous logistic regression analysis focused on the personal,
      demographic and sociocultural background of CAM users. RESULTS: CAM use in the
      last 12 months was reported by 21.9% of the participants in 1993 and by 29.5% in
      1999. CAM use among those exhibiting either physical or psychological problems
      was in the ratio of two to one. There was a trend from alternative variants of
      CAM (homeopathy) to complementary ones (massage, osteopathy, acupuncture). The
      vast majority of CAM use was in addition to conventional therapies. Predictors of
      CAM use were, among others, attribution of physical complaints to stress and
      other psychological variables, very low education level in parents, and lacking
      political interest. CONCLUSIONS: Besides the sociocultural background,
      characteristics such as the psychological attribution style play an important
      role in CAM use. CAM use in Switzerland is mainly of a complementary rather than
      an alternative nature.

PMID- 16999880
TI  - Childhood adversities and risk for suicidal ideation and attempts: a longitudinal
      population-based study.
AB  - BACKGROUND: Developmental adversities may be risk factors for adult suicidal
      behavior, but this relationship has rarely been studied prospectively. The
      present study examined the association between childhood adversities and new
      onset suicidal ideation and attempts in an adult population-based sample. METHOD:
      The study used a large community mental health survey (the Netherlands Mental
      Health Survey and Incidence Study; n=7076, age range 18-64 years). Logistic
      regression analyses were used to evaluate the relationship between childhood
      adversities and new onset of suicidal ideation and attempts over 3 years of
      longitudinal follow-up. RESULTS: During the study period 85 new cases of suicidal
      ideation and 39 new onset suicide attempts were observed. The incidence rate for
      new suicide ideation was 0.67% per year and the incidence rate for new suicide
      attempts was 0.28% per year. Childhood neglect, psychological abuse and physical
      abuse were strongly associated with new onset suicidal ideation and suicide
      attempts. Odds ratios (ORs) ranged from 2.80 to 4.66 for new onset suicidal
      ideation and from 3.60 to 5.43 for new onset suicide attempts. The total number
      of adversities reported had a strong graded relationship to new onset suicidal
      ideation and attempts. These associations remained significant after controlling
      for the effects of mental disorders. CONCLUSIONS: Childhood abuse and multiple
      adversities are strongly associated with future suicidal behavior and the mental
      disorders assessed in the present study do not fully account for this effect. A
      comprehensive understanding of suicidal behavior must take childhood adversities
      into account.

PMID- 16999882
TI  - [The global disease control--a race against time].

PMID- 16999883
TI  - [Global burden of disease--a race against time].
AB  - Low-income communities will within the next decades undergo rapid changes. The
      burden of non-communicable diseases (NCDs), such as diabetes, cardio-vascular
      disease and cancer, will comprise an increasing proportion of the total disease
      burden. The results of projections indicate that the already constrained health
      systems will face a double burden of disease, in which HIV/AIDS and other common
      infectious diseases will co-exist with the new NCDs. In order for preventive
      measures directed towards NCD to be cost-effective, these have to be implemented
      within the next 10-20 years.

PMID- 16999884
TI  - [Global health--the ethical responsibility of the pharmaceutical industry].
AB  - Health is a global concern and all stakeholders in society--including the
      pharmaceutical industry--have an ethical responsibility to contribute to promote
      health. At Novo Nordisk, we have decided to focus on defeating diabetes since
      this is the area where the company can make the biggest difference. Financial
      viability goes hand in hand with environmental and social responsibility, not
      only in the external stakeholder dialogue, but also in the quest for attraction
      and retention of the best possible staff. Examples of the ethical obligations of
      a pharmaceutical company are presented, as are classical dilemmas faced by the
      industry.

PMID- 16999885
TI  - [International health research: priorities and commitment].
AB  - Of the global budget for health research, only 10% is spent on the disease burden
      of 90% of the world's population. Investments for international health research
      are lacking, hampering health for the poor. Effective vaccines against the world
      killers HIV, malaria and tuberculosis still do not exist. However, in order to
      understand the obstacles to implementing existing effective interventions,
      scaling up research for new drugs and vaccines must be accompanied by research in
      health systems, to understand the obstacles to implement existing effective
      interventions. The task demands political and private sector commitment.

PMID- 16999886
TI  - [There are too many chefs in Africa].
AB  - Available interventions could prevent 6 out of 10 million deaths in children
      younger than 5 years of age every year. The health sector and donor agencies bear
      responsibility for not using these interventions. The UN's Millennium Development
      Goals are a step in the right direction towards a focused approach. The poor and
      illiterates are most seriously affected by a low quality of care. The hospital
      sector suffered unreasonably in the 1980's and now has to fight a vicious circle
      of mistrust, low quality, collapsed administrative and professional institutions
      and lack of financing. New and old interventions should be evaluated constantly
      to maximise efficiency.

PMID- 16999887
TI  - [Development assistance in the health area--a global perspective].
AB  - Countries like Mozambique and Tanzania have shown that some of the poorest
      countries in the world can make significant health gains with relatively limited
      additional financial resources. The global health development efforts are focused
      on the three health-related Millennium Development Goals, which have inspired the
      launch of important new Global Health Partnerships. The more focused global
      health development effort, matched with increased investments in health
      development, raises the prospective of further health gains in the coming years.

PMID- 16999888
TI  - [Denmark's global responsibility--the Danish development assistance policy].

PMID- 16999889
TI  - [Health effects of migration].
AB  - Migration may have a negative impact on the health status of migrants due to the
      multiple physical and psychosocial strains affecting them during the entire
      process of migration. Being exposed to these strains and suffering different
      kinds of losses might lead to stress and increase in risk behaviour among
      migrants, thereby impacting negatively on their somatic and mental health. The
      negative health effects of migration are mediated by the individual's resources
      e.g. social support.

PMID- 16999890
TI  - [Access to health care for migrants].
AB  - Migrants include a broad category of individuals moving from one place to
      another, either forced or voluntarily. Ethnicity and migration are interacting
      concepts which may act as determinants for migrants' health and access to health
      care. This access to health care may be measured by studying utilisation patterns
      or clinical outcomes like morbidity and mortality. Migrants' access to health
      care may be affected by several factors relating to formal and informal barriers.
      Informal barriers include economic and legal restrictions. Formal barriers
      include language and psychological and sociocultural factors.

PMID- 16999891
TI  - [Access to health care for undocumented immigrants. Rights and practice].
AB  - The purpose of this article is to illuminate undocumented immigrants' right to
      access to health care and their access in practice. Undocumented immigrants have
      a right to equal access to health care. Access to more than emergency health care
      in Denmark is dependent on immigration status. Medical doctors' duty to treat
      does not apply to non-emergency health needs, and the options existing in this
      situation remain ambiguous. In practice, undocumented immigrants in Denmark are
      able to receive more than emergency health care through unofficial networks of
      health care providers.

PMID- 16999892
TI  - [Undergraduate and postgraduate education in international health].
AB  - The aim of this article is to provide information about possibilities for medical
      students and doctors to obtain knowledge about international health. Increasing
      globalisation requires knowledge about international health in such way that
      Danish doctors are able to diagnose and treat patients, regardless of the
      patient's nationality and ethnic background. Denmark has a global responsibility
      towards low and middle income countries to increase the standard of health.
      Increased knowledge and research in these countries is important both at an
      undergraduate and postgraduate level.

PMID- 16999893
TI  - [International health at home: bringing the experiences back home with you].
AB  - International Health research conducted under extreme conditions in low-income
      countries may lead to a better understanding of epidemics in high-income
      countries, by questioning assumptions which are important in these countries.
      Examples are given of how observations in Guinea-Bissau have led to
      reinterpretation of the decline in measles mortality, of the polio model, and of
      the impact of stopping vaccinations after eradication in the industrialised
      countries.

PMID- 16999894
TI  - [Global transition in health].
AB  - Global epidemiological transition reflected in changed patterns of death and
      diseases was first described by Omran; decreasing death and disease rates from
      infectious diseases, particularly in children and the young, are followed by
      decreased fertility rate and increased longevity, and by degenerative, and man
      made diseases in ageing populations. Omran could not foresee the HIV/AIDS
      pandemic or the dramatic fall in longevity and fertility in, for example, Russia.
      But his model remains of value for health planners and politicians. We advocate
      for research in the interplay between diseases, populations and systems in a
      world in fast transition.

PMID- 16999895
TI  - [International nutrition and health].
AB  - Malnutrition is the major underlying determinant of global disease and death.
      Maternal undernutrition and the premature introduction of complementary foods
      with low energy-nutrient density lead to low birth weight, impaired growth and
      intellectual development, and high mortality due to infectious diseases. More
      than 5 million of the 10 million annual child deaths are due to underlying
      undernutrition. As a result of rural-urban migration and access to refined sugar
      and fat, overnutrition and chronic diseases are also becoming an increasing
      problem among the poor.

PMID- 16999896
TI  - [Child and adolescent health in a European perspective--a new WHO-strategy].
AB  - In general, children and adolescents in the WHO European Region have better
      nutrition, health and development today than ever before. However, there are
      striking inequalities in health status across the 52 countries in the Region with
      over ten-fold differences in infant and child mortality rates. Inequalities are
      also growing within countries, and several health threats are emerging. To
      prevent this, the WHO Regional Office for Europe has developed a European
      strategy for child and adolescent health and development. The strategy, and its
      tool kit for implementation, aims to assist Member States in formulating their
      own policies and programmes.

PMID- 16999897
TI  - [International child health].
AB  - International child health has improved. Better healthcare strategies, like IMCI,
      have contributed implementing basic interventions: vaccinations, nutrition
      supplement, oral rehydration and antibiotics. But 11 million children still die
      every year before they turn five, most from infectious diseases and neonatal
      complications, over half associated with malnutrition. Conditions we could
      prevent and treat. One of UN's Millennium Development Goals is to reduce child
      mortality. However child health is more than mortality and morbidity indicators,
      it includes growth and development.

PMID- 16999898
TI  - [Global mental health].
AB  - Mental disorders contribute significantly to the Global Burden of Disease. Four
      out of the ten diseases with the highest burden are psychiatric. About 25% of all
      individuals develop one or more psychiatric and behavioural disorders during
      their lifetime. Unipolar depression ranges as the leading mental disorder with
      respect to Disability Adjusted Life Years. The major psychiatric disorders like
      schizophrenia and depression are found in all cultures and result in significant
      disability. The cost of mental disorders worldwide needs to be more generally
      recognized.

PMID- 16999899
TI  - [Metabolic syndrome in a global perspective. Significance for public health].
AB  - The term "metabolic syndrome" refers to the clustering of a number of
      cardiovascular risk factors (obesity, hypertension, dyslipidemia and
      hyperglycemia) believed to be related to insulin resistance. The prevalence of
      each of these diseases as well as the metabolic syndrome is increasing world
      wide. Obesity, hypertension, dyslipidemia and diabetes are no longer diseases of
      the wealthy. By 2025, three out of four people with diabetes will be living in
      3rd world countries, and similar trends are likely for the other components of
      the syndrome. Preventive action is urgently needed, and studies in China and
      India have proven to be effective.

PMID- 16999900
TI  - [HIV/AIDS spread and influence on other health-related Millennium Development
      Goals].
AB  - HIV/AIDS is threatening the development of countries with high HIV prevalence.
      This article analyses the impact of HIV/AIDS on the Millennium Development Goals
      for Health. The analysis is based on a literature survey on the impact of HIV on
      child health, maternal mortality, tuberculosis and malaria. We find a strong
      correlation between HIV and child mortality and HIV and TB. We conclude that, in
      order to reach the Millennium Development Goals, health strategies must include a
      comprehensive and coordinated approach to fight major health problems including
      improved resource allocation.

PMID- 16999901
TI  - [Trends in global antibiotic resistance].
AB  - Antibiotic resistance is an increasing problem world wide, although in some areas
      the increase in resistance is slow, as in the Nordic countries. Multiresistant
      staphylococci, Enterobaceriaceae and Mycobacterium tuberculosis are already
      causing increased morbidity, mortality and huge costs in health budgets. New
      effective antibiotics will not be available for the next 10-15 years, since the
      pharmaceutical industry has lost interest in antibiotics. The major determinant
      in this field, in order to save the activity of the known antibiotics, is the
      control of antibiotic use.

PMID- 16999902
TI  - [Acute pesticide poisoning--a global public health problem].
AB  - Following the intensification of agriculture and the promotion of agro-chemicals
      in low and middle income countries, acute pesticide poisoning has become a major
      public health problem with more than 300,000 deaths each year around the world.
      The easy availability of highly toxic pesticides in the homes of farming
      communities has made pesticides a preferred choice for suicide with an extremely
      high case fatality. Similarly, the extensive use of pesticides exposes the
      community to both long-term and acute occupational health problems. A concerted
      effort is urgently needed to address this problem.

PMID- 16999903
TI  - [Gender differences in response to preventive health care interventions. Do we
      have to treat girls and boys differently to treat them equally?].
AB  - In spite of well-recognised differences in morbidity patterns among boys and
      girls, differences in their response to common interventions like vaccinations
      have rarely been considered. Our research in vaccinations and vitamin A
      supplementation has suggested sex differences in the response to these
      interventions. If these observations reflect a general pattern, it may be that,
      in order to be treated equally, boys and girls should be treated differently.

PMID- 16999904
TI  - [Consequences of collective violence with special focus on gender perspective].
AB  - There is increasing focus on the gender perspective related to the consequences
      of collective violence. Women run a greater risk of being victims of sexual
      violence, but few studies have focused on gender differences with respect to
      physical violence, sexual violations and the impact on health. Further research
      is needed on these issues as well as research on the identification of evidence
      based interventions.

PMID- 16999905
TI  - [Possibility for the health sector to actively contribute to peace-making and
      peace-keeping].
AB  - Conflict is one of the leading causes of death, disease and suffering. In the
      past, physicians mainly contributed to peace processes through humanitarian
      relief of suffering. Physicians can also play an active role in the prevention of
      violent conflict and in rehabilitation in post-conflict societies. This article
      is a brief overview of current knowledge about the active role which health
      personnel can play in peace processes. This is described in more detail in
      international scientific journals under the terms ''Peace through Health'' and
      ''Health as a Bridge to Peace''.

PMID- 16999906
TI  - [Armed conflict and access to emergency treatment in the occupied West Bank of
      Palestine--secondary publication].
AB  - Research on the health consequences of armed conflicts is still in its infancy.
      Systematic medical data collection among emergency department contacts at three
      hospitals in the occupied West Bank of Palestine showed that patients delayed by
      the Israeli occupation were more likely to be admitted to hospital than other
      patients. The occupation of Palestine has resulted in severe restriction to the
      civil population's freedom of movement that influences access to health care,
      among a number of other serious problems. This presents a serious violation of
      the Geneva Conventions.

PMID- 16999911
TI  - [Doping preparations use among patients in general practice].

PMID- 16999912
TI  - [Neurological aspects of stuttering].
AB  - Stuttering is characterised by repetitions, prolongations and pausing while
      speaking. Researchers have looked for many explanations. However, the cause of
      stuttering remains unknown. In recent years, structural abnormalities in the
      speech-related structures of the central nervous system have been brought into
      focus as a cause of stuttering. Research has shown signs of a lateral hemisphere
      asymmetry, abnormalities in the basal ganglia, dysfunction in the supplementary
      motor area and/or a dysfunction in the coordination of the cerebellum. This
      article is a review of this part of the literature.

PMID- 16999913
TI  - [Subclinical hypothyroidism--a condition that must be treated?].
AB  - Subclinical hypothyroidism, defined as serum thyrotropin above the upper
      reference limit with normal estimates of free thyroxin in serum, has a prevalence
      in Denmark of 2%. Several investigations have shown that patients with
      subclinical hypothyroidism have subtle symptoms and signs of mild thyroid
      failure. Whether these patients require treatment or not is a controversial issue
      due to a lack of convincing evidence regarding the beneficial effects of hormone
      replacement, especially in patients with serum TSH <10 mU/L. However, when it
      comes to treatment of pregnant or fertile women planning pregnancy, no doubt
      prevails, as normal thyroid function is important for optimal pregnancy outcome.

PMID- 16999914
TI  - [Taxanes in metastatic breast cancer. An analysis of a systematic Cochrane
      review].

PMID- 16999915
TI  - [Use of anabolic androgenic steroids, growth hormone and erythropoietin by
      patients in general practice].
AB  - INTRODUCTION: The goal of this study was to investigate the use and side effects
      of anabolic androgenic steroids (AASs), growth hormone (GH), erythropoietin (EPO)
      and other enhancing drugs by patients in general practice. MATERIALS AND METHODS:
      In a questionnaire, 702 general practitioners (GPs) in Denmark were asked to
      estimate the number of their patients who within the preceding year had admitted
      to using or were highly suspected of having used AASs, GH, EPO or other enhancing
      drugs. In addition, they were asked to describe the possible side effects of
      their use. RESULTS: Of 571 eligible GPs, 119 had within the preceding year
      treated patients who had admitted to or were highly suspected of having used
      AASs, GH, EPO or other enhancing drugs. 182 users were reported by the GPs during
      that period; 180 (99%) were males, and 156 (86%) were between 20 and 40 years of
      age. 125 of the patients (69%) had admitted the use to the GP; AASs had been used
      by 123 patients (98%). EPO was not reported in any case, but GH had been used by
      9 patients (7%). 127 (70%) of the patients had experienced side effects, and 87
      (49%) had contacted the GP due to these side effects. CONCLUSION: The use and
      side effects of AAS are commonly reported in general practice, whereas the use
      and side effects of GH and EPO seem to be uncommon. Their use is mainly by men
      under 40 years of age. The use of AAS is often connected with dermatological and
      musculoskeletal side effects. It is recommended also to consider possible use of
      AASs when consulted by a patient with unexplained symptoms of cardiovascular
      disease, psychological or sexual dysfunction, gynaecomastia or liver dysfunction.

PMID- 16999916
TI  - [Waste of resources as a result of cancelled or delayed diagnostic imaging of
      hospitalized patients].
AB  - INTRODUCTION: When diagnostic imaging is cancelled on short notice or an
      examination is delayed, the Imaging Department suffers a loss. Based on voluntary
      reporting of such events, we have estimated the total expenditure involved.
      MATERIALS AND METHODS: For one year an orderly reported cases in which, when he
      arrived to fetch an inpatient, the latter was no longer in the ward or was not
      ready. From this study material we estimated the waste of time for the staff and
      the total price of cancelled or delayed examinations, spread over various
      categories. This sum is related to the estimated cost of one preventive measure:
      letting the orderly check in the hospital's electronic administrative system
      whether the patient is still in the ward indicated. RESULTS: A total of 436
      cancelled or delayed examinations were reported in 2004. In 249 cases the
      examination was cancelled, and since the recorded total number of cancellations
      was 1,435, we estimate the total number of cancelled or delayed exams to be
      approximately 2,500 (1,435 x 436/249). The estimated total waste of time is 66
      weeks (1(1/2) years' work). The estimated price of the cancelled or delayed
      examinations is 2.4 million Danish kroner. When we relate the savings if the
      problem is solved to the cost of prevention, we find that it would be clearly
      profitable to address fluoroscopy and CT scanning. Conversely, addressing bone X
      rays would generate a loss. CONCLUSION: We conclude that there is a very large
      waste of resources caused by cancelled or delayed imaging examinations.

PMID- 16999917
TI  - [Selective screening for hepatitis B in pregnant women in Denmark].
AB  - INTRODUCTION: The objective of this study was to evaluate the implementation of
      the present Danish selective screening strategy for possible hepatitis B
      infection in pregnant women who themselves or whose partners originate from
      medium- or high-endemic hepatitis B areas of the world. We also investigated
      whether children of hepatitis B carriers were treated with immunoglobulin and
      vaccination. MATERIALS AND METHODS: We did a retrospective study of 1,924 birth
      notification forms of women who had delivered between 1 January and 30 June 2000
      in Frederiksborg County, Denmark. Women were selected who had foreign-sounding
      names. The hospital case notes were examined to determine the women's countries
      of origin and their hepatitis B screening status. We then contacted the
      Department of Clinical Immunology of each hospital and the Danish State Serum
      Institute to double-check the women's screening status. RESULTS: The study
      included 210 women, who made up nearly 11% of this cohort. Sixty-eight (32%) of
      the women had been tested according to the guidelines. One woman was a hepatitis
      B carrier. Her child had received immunoglobulin and vaccination within 24 hours
      of birth. CONCLUSION: This study indicates that a selective antenatal screening
      program for hepatitis B is difficult to implement in daily clinical practice. The
      fact that only one third of this well-defined risk group had been tested for
      hepatitis B emphasizes the need for a universal antenatal screening program.

PMID- 16999918
TI  - [Port-a-cath insertion].

PMID- 16999919
TI  - [Patient injuries in response to anaesthetic procedures: cases evaluated by the
      Danish Patient Insurance Association--secondary publication].
AB  - We investigated the Danish Patient Insurance Association files of patients, who
      were given financial compensation, because of an injury caused by an anaesthetic
      procedure. In the six-year-period 1996-2002, 374 patients were compensated in
      total 8.0 million euros for an injury caused by an anaesthetic procedure. Some
      anaesthetic complications may result in severe disability, whereby the financial
      compensation to the suffering patients is high. We estimate that approximately
      0.2 per 1,000 of all patients receiving anaesthesia may develop complications
      that entitle them to financial compensation.

PMID- 16999920
TI  - [Noninferiority and equivalence randomized trials: lessons and reservations-
      secondary publication].
AB  - A noninferiority trial seeks to determine, whether a new intervention is not
      inferior to a reference intervention within a prespecified noninferiority
      interval (-Delta to 0) for the primary outcome. An equivalence trial aims to
      determine whether two interventions have a similar effect within a prespecified
      interval (-Delta to +Delta). These trials are controversial and difficult to
      grasp and very often poorly reported and conducted. Any claims regarding efficacy
      of new treatments, based on these trials, should be interpreted with caution, and
      it should be noted that Delta is often far too large to be clinically meaningful.

PMID- 16999921
TI  - [Perirectal, retroperitoneal, intraperitoneal and mediastinal gas after stapled
      haemorrhoidopexy].
AB  - We describe a case of perirectal, retroperitoneal, intraperitoneal and
      mediastinal gas after stapled haemorrhoidopexy. A previously healthy man aged 38
      suffered after the operation from abdominal pain and scrotal emphysema.
      Anorectoscopy revealed a technical failure, as the staple line was found 6-7 cm
      orally to the dentate line. The patient was successfully treated with intravenous
      antibiotics and oxygen and recovered without further surgery. In case of alarm
      symptoms such as abdominal pain or fever after stapled haemorrhoidopexy, a plain
      abdominal X-ray should be done to verify or exclude retroperitoneal gas.

PMID- 16999927
TI  - Geographic variability in alcohol-related crashes in response to legalized Sunday
      packaged alcohol sales in New Mexico.
AB  - On July 1, 1995 the state of New Mexico lifted its ban on Sunday packaged alcohol
      sales. Legislation lifting the ban included a local option allowing individual
      communities within the state to hold an election to reinstitute the ban on Sunday
      packaged alcohol sales. Previous research has shown a clear statewide increase in
      alcohol-related crash and crash fatality rates after the ban was lifted. The goal
      of this study is to measure county-level variability in changes in alcohol
      related crash rates while adjusting for county socio-demographic characteristics,
      spatial patterns in crash rates and temporal trends in alcohol-related crash
      rates. Bayesian hierarchical binomial regression models were fit to the observed
      quarterly crash counts for all counties between July 1, 1990 and June 30, 2000.
      Results show marked variability in the impact of legalized Sunday packaged
      alcohol sales on alcohol-related crash rates. Relative risks of an alcohol
      related crash for the post-repeal versus pre-repeal period vary across counties
      from 1.04 to 1.90. Counties with older population suffered a greater negative
      impact of legalized Sunday packaged alcohol sales. Counties with communities that
      quickly passed the local option to re-ban packaged sales on Sundays were able to
      mitigate most of the deleterious impact of increased alcohol availability that
      was observed across the state.

PMID- 16999928
TI  - Re-introducing bacteria in mosquitoes--a method for determination of mosquito
      feeding preferences based on coloured sugar solutions.
AB  - In this study, sugar-feeding was investigated as a possible means of re
      introducing bacteria into mosquito midguts with the aim of identifying bacteria
      that are suitable for creating paratransgenic mosquitoes. In a paratransgenic
      approach, bacteria are utilised to deliver effector molecules capable of
      inhibiting pathogen development in the midgut of the vector. To determine if
      mosquitoes discriminate between sterile sugar solutions and sugar solutions with
      bacteria, a method for screening mosquito feeding preferences was developed. This
      method was tested for Aedes aegypti, Anopheles arabiensis and An. gambiae s.s.
      mosquitoes and is based on a dual-choice test of solutions labelled with food
      dyes. Three different tests (dye/colour detection, sugar detection and sugar
      concentration detection) were performed to evaluate the method, after which
      bacteria previously isolated from mosquitoes were used in the experiments. It was
      shown that mosquitoes do not discriminate between sugar solutions with or without
      these bacteria indicating that sugar-feeding is a possible means to introduce
      bacteria into mosquitoes. Furthermore, two different setups of the method were
      used, enabling us to differentiate between tactile/taste and olfactory responses.
      The method described in this paper is easy to use, cost-effective and allows
      broad screening of mosquito sugar-feeding preferences.

PMID- 16999929
TI  - Protective immunity induced by phage displayed mitochondrial related peptides of
      Schistosoma japonicum.
AB  - New antigens and strategies are necessary for vaccine development against
      schistosomiasis japonica. Using a pool of 43 high titred anti-SWA sera from
      individuals residing in an Schistosoma japonicum endemic area of China, we have
      cloned a S. japonicum gene by cDNA library screening. The recombinant Sj338
      protein has 44-46% identity to a mitochondrial precursor receptor protein of
      humans and rats. Immunization of mice with the recombinant Sj338 conferred 27-32%
      (p<0.01) reduction in worm burdens following cercarial challenge. In an effort to
      identify protective epitopes in Sj338 and increase the level of protection, we
      screened a random 12-mer peptide library constructed in M13 using a polyspecific
      anti-Sj338 rabbit serum. After five rounds of biopanning, we identified 30
      reactive clones consisting of 11 distinct peptide sequences. These clones shared
      limited primary sequence homology with the recombinant Sj338 protein. Anti-sera
      raised against these phage clones recognized recombinant Sj338 and SWAP by
      Western blot. In murine vaccination experiments using whole recombinant phage
      without adjuvant, four of these clones demonstrated worm reductions of 11.6-25.1%
      (p=ns - 0.05) compared to M13 vaccinated animals. Animals vaccinated with all
      four of these phage demonstrated 34.2% (p<0.01) worm reduction compared to
      controls vaccinated with M13 clone. These data suggest that mimotope peptides are
      potential vaccine candidates for S. japonicum.

PMID- 16999930
TI  - Musculoskeletal problems in Iranian hand-woven carpet industry: guidelines for
      workstation design.
AB  - Long hours of static work with awkward posture at traditionally designed looms
      can cause high prevalence of musculoskeletal disorders (MSDs) among carpet
      weavers. A comprehensive study was conducted in this industry with the objectives
      of determination of MSDs symptoms prevalence; identification of major factors
      associated with MSDs symptoms in carpet weaving occupation; and development of
      guidelines for weaving workstation design. In the present paper, this ergonomics
      study is presented. The study consisted of two phases. In the first phase, MSDs
      symptoms in nine Iranian provinces were surveyed by questionnaire among 1439
      randomly selected weavers. Working posture and weaving workstations were
      ergonomically assessed as well. The results of this phase revealed that symptoms
      from the musculoskeletal system occurred in high rate among weavers with the
      prevalence significantly higher than that of the general Iranian population
      (P<0.001). It was found that the majority of ergonomics shortcomings originated
      from ill-designed weaving workstation. Based on the findings, some general
      guidelines for workstation design were presented. In the second phase,
      considering the general guidelines, an adjustable workstation was designed and
      constructed. To develop quantitative guidelines for optimizing workstation set
      up, in the laboratory, nine sets of experimental conditions were tested, and
      working posture and weavers' perceptions were measured. The results of this lab
      work showed that working posture was acceptable for both the researchers and the
      weavers when the weaving height was adjusted 20 cm above the elbow height and a
      high seat with forward slope was used. By combining the results of the two
      phases, guidelines for weaving workstation design were presented. In this
      ergonomics-oriented workstation, loom is vertical. Seat, loom and weaving heights
      are adjustable. There is enough leg room under the loom. The seat with 10 degrees
      forward slope is adjusted 15 cm above the popliteal height of the weaver. Weaving
      height is set at 20 cm above the elbow height. It is believed that the
      recommended workstation improves working posture and results in reduced postural
      stress on weavers' bodies and, consequently, reduced prevalence of MSDs symptoms.

PMID- 16999931
TI  - Mapping of user interfaces on electronic appliances.
AB  - The purpose of this study was to investigate mapping of user interfaces on
      consumer electronic appliances. A digital clock with five different interface
      modes was chosen for the experiment. Forty elderly subjects (above 65 years) and
      40 middle-aged subjects (45-64 years) participated in the study. Every subject
      had to complete three different tasks, namely time setting, alarm time setting
      and date setting. The researchers investigated what problems were encountered
      when performing these tasks and collected data such as operational time, the
      number of total inputs, subjective estimation and interview information. The
      findings of this study indicated that the interface modes had significant effects
      on operational time, the number of total inputs and subjective estimation.
      Finally, the study confirms that when the spatial relationship between buttons
      and display contents are clearly indicated, the operation is easier to complete.

PMID- 16999932
TI  - Characterization and in vitro evaluation of spherulites as sequestering vesicles
      with potential application in drug detoxification.
AB  - The aim of the present investigation was to prepare and characterize lecithin
      spherulites as parenteral drug sequestering agents with potential application in
      the treatment of drug overdose and chemical poisoning. The spherulites
      (approximately 200 nm) obtained by controlled hydration and shearing of lipid
      alcohol mixtures, revealed unexpected differences in the physical properties of
      the bilayer when compared to liposomes. Differential scanning calorimetry, 31
      phosphorus nuclear magnetic resonance, and pH-sensitive pyranine steady-state
      fluorescence studies indicated that although spherulites retained the typical
      bilayer conformation, the arrangement of the phospholipid molecules was perturbed
      relative to native liposome bilayer. The loosened packing of the phospholipids in
      bilayers was strongly supported by the relative ease with which spherulites lost
      the established pH-gradient. This permeability problem was overcome via
      incorporation of cholesterol in the bilayer. Subsequently, albumin/buffer
      components were encapsulated in these spherulites and the drug sequestration
      potential for detoxification application was examined. Citrate pH-gradient
      spherulites accumulated 75% of external haloperidol while those loaded with
      approximately 20% (w/w) albumin were able to take up 45% of haloperidol and 91
      95% of taxanes (docetaxel and paclitaxel). In cytotoxicity studies, the
      competitive internalization of docetaxel by albumin-loaded spherulites resulted
      in an increase of the IC50 value for the free drug. Thus, the spherulite
      technology could be a versatile approach for actively sequestering toxins in the
      blood and for reducing the adverse effects by altering the pharmacokinetics and
      biodistribution of overdosed drugs.

PMID- 16999933
TI  - Configuration of influenza hemagglutinin fusion peptide monomers and oligomers in
      membranes.
AB  - The 20 N-terminal residues of the HA2 subunit of influenza hemagglutinin (HA),
      known as the fusion peptide, play a crucial role in membrane fusion. Molecular
      dynamics simulations with implicit solvation are employed here to study the
      structure and orientation of the fusion peptide in membranes. As a monomer the
      alpha-helical peptide adopts a shallow, slightly tilted orientation along the
      lipid tail-head group interface. The average angle of the peptide with respect to
      membrane plane is 12.4 degrees . We find that the kinked structure proposed on
      the basis of NMR data is not stable in our model because of the high energy cost
      related to the membrane insertion of polar groups. Because hemagglutinin-mediated
      membrane fusion is promoted by low pH, we examined the effect of protonation of
      the Glu and Asp residues. The configurations of the protonated peptides were
      slightly deeper in the membrane but at similar angles. Finally, because HA is a
      trimer, we modeled helical fusion peptide trimers. We find that oligomerization
      affects the insertion depth of the peptide and its orientation with respect to
      the membrane: a trimer exhibits equally favorable configurations in which some or
      all of the helices in the bundle insert obliquely deep into the membrane.

PMID- 16999934
TI  - Effect of heme oxygenase-1 on the vulnerability of astrocytes and neurons to
      hemoglobin.
AB  - The heme oxygenase (HO) enzymes catalyze the rate-limiting step of heme
      breakdown. Prior studies have demonstrated that the vulnerability of neurons and
      astrocytes to hemoglobin is modified in cells lacking HO-2, the constitutive
      isoform. The present study assessed the effect of the inducible isoform, HO-1.
      Wild-type astrocytes treated for 3-5 days with 3-30 microM hemoglobin sustained
      no loss of viability, as quantified by LDH and MTT assays. The same treatment
      resulted in death of 25-50% of HO-1 knockout astrocytes, and a 4-fold increase in
      protein oxidation. Cell injury was attenuated by transfer of the HO-1 gene, but
      not by bilirubin, the antioxidant heme breakdown product. Conversely, neuronal
      protein oxidation and cell death after hemoglobin exposure were similar in wild
      type and HO-1 knockout cultures. These results suggest that HO-1 induction
      protects astrocytes from the oxidative toxicity of Hb, but has no effect on
      neuronal injury.

PMID- 16999935
TI  - COPI-mediated retrograde transport is required for efficient gamma-secretase
      cleavage of the amyloid precursor protein.
AB  - Sequential cleavage of the amyloid precursor protein (APP) by beta- and gamma
      secretases results in the production of beta-amyloid peptide, which is a key
      determinant in Alzheimer's disease. Since several putative locations for gamma
      secretase cleavage have been identified along the secretory pathway, trafficking
      of APP may be of importance for beta-amyloid peptide production. Here we have
      studied the role of retrograde transport in APP processing. We found that APP
      interacts with the beta subunit of the coatomer protein I (COPI) complex, which
      is involved in retrograde transport. In line with a role of retrograde
      trafficking in APP transport, inhibition of COPI-dependent transport altered APP
      trafficking, decreased APP cell surface expression, and coincided with a profound
      reduction in gamma-secretase cleavage. These results suggest that COPI-dependent
      retrograde transport is important for APP processing and influences production of
      beta-amyloid peptide.

PMID- 16999937
TI  - Cryptotanshinone from Salvia miltiorrhiza BUNGE has an inhibitory effect on TNF
      alpha-induced matrix metalloproteinase-9 production and HASMC migration via down
      regulated NF-kappaB and AP-1.
AB  - Matrix metalloproteinases (MMP-9 and MMP-2) production and smooth muscle cell
      (SMC) migration may play key roles in the phathogenesis of neointima formation
      and atherosclerosis. Especially inducible MMP-9 expression was directly involved
      in the cancer cell invasion and SMC migration through vascular wall. In this
      study, we reveal that cryptotanshinone (CT) purified from Salvia miltiorrhiza
      BUNGE had an inhibitory effect on MMP-9 production and migration of human aortic
      smooth muscle cells treated with TNF-alpha in a dose-dependent manner. The down
      regulation of transcription of MMP-9 mRNA was evidenced by RT-PCR and MMP-9
      promoter assay using luciferase reporter gene. Eletrophoretic mobility shift
      assay showed NF-kappaB and AP-1 nuclear translocations were suppressed. In
      addition, Western blot analysis indicated that extracellular signal regulated
      kinase 1 and 2, p38 and JNK MAP kinase signaling pathways were inhibited. From
      the results, it is suggested that CT has anti-atherosclerosis and anti-neointimal
      formation activity.

PMID- 16999936
TI  - APOBEC-1 and AID are nucleo-cytoplasmic trafficking proteins but APOBEC3G cannot
      traffic.
AB  - Human APOBEC3G (hA3G) is a member of the APOBEC-1 related protein (ARP) family of
      cytidine deaminases. hA3G functions as a natural defense against endogenous
      retrotransposons and a multitude of retroviruses, most notably human
      immunodeficiency virus type 1 (HIV-1). Nothing is known about the cellular
      function of hA3G, however, upon HIV-1 infection hA3G functions as an antiviral
      factor by mutating viral single-stranded DNA during reverse transcription.
      Whereas homologous deaminases such as APOBEC-1 and AID act on RNA and DNA,
      respectively, in the cell nucleus, hA3G mutagenic activity appears to be
      restricted to the cytoplasm. We demonstrate that hA3G is not a nucleo-cytoplasmic
      shuttling protein like APOBEC-1 and AID, but is strongly retained in the
      cytoplasm through a mechanism that involves both the N and C-terminal regions of
      the protein.

PMID- 16999938
TI  - 20 years of NF-kappaB.

PMID- 16999939
TI  - Resveratrol modulates phorbol ester-induced pro-inflammatory signal transduction
      pathways in mouse skin in vivo: NF-kappaB and AP-1 as prime targets.
AB  - Functional abnormalities of intracellular signaling network cause the disruption
      in homeostasis maintained by critical cellular components, thereby accelerating
      premalignant and malignant transformation. Multiple lines of evidence suggest
      that an elevated expression of cyclooxygenase-2 (COX-2) is causally linked to
      tumorigenesis. The exposure to oxidative/pro-inflammatory stimuli turns on
      signaling arrays mediated by diverse classes of kinases and transcription
      factors, which may lead to aberrant expression of COX-2. We have attempted to
      unravel the signal transduction pathways involved in elevated COX-2 expression in
      mouse skin stimulated with a prototype tumor promoter 12-O-tetradecanoylphorbol
      13-acetate (TPA) and its modulation by resveratrol, a phytoalexin known to exert
      potential chemopreventive effects. Our study revealed that topical application of
      TPA induced COX-2 expression in mouse skin via activation of nuclear factor
      kappaB (NF-kappaB), which is regulated by upstream IkappaB kinase (IKK) or
      differentially by mitogen-activated protein (MAP) kinases. Besides NF-kappaB, the
      p38 MAP kinase-mediated activation of activator protein-1 (AP-1) has also been
      attributed to TPA-induced COX-2 expression in mouse skin. Among the MAP kinases,
      extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase have been
      shown to regulate TPA-induced NF-kappaB activation, while p38 MAP kinase and c
      Jun-N-terminal kinase are preferentially involved in TPA-induced activation of AP
      1 in mouse skin in vivo. This commentary focuses on resveratrol modulation of
      intracellular signaling pathways involved in aberrant COX-2 expression in TPA
      stimulated mouse skin to delineate molecular mechanisms underlying antitumor
      promoting effects of resveratrol.

PMID- 16999940
TI  - Protection of nigral cell death by bilateral subthalamic nucleus stimulation.
AB  - In Parkinson disease (PD), the subthalamic nucleus (STN) becomes hyperactive
      (disinhibited), which is reported to cause excitotoxic damage to midbrain
      dopaminergic neurons. Here, we examined whether silencing of the hyperactive STN
      by chronic bilateral deep brain stimulation (DBS) increased the survival of
      midbrain dopaminergic neurons in a rat model of PD. High-precision design-based
      stereologic examination of the total number of neurons and tyrosine tydroxylase
      (TH) immunoreactive neurons in the substantia nigra pars compacta revealed that
      STN DBS resulted in a significant survival of these neurons. These data provide
      the first evidence in vivo that bilateral STN DBS is useful for protecting
      midbrain dopaminergic neurons from cell death in PD.

PMID- 16999941
TI  - Genetic influence on neurogenesis in the dentate gyrus of two strains of adult
      mice.
AB  - Previous studies have suggested that there is a genetic influence on the
      regulation of cell proliferation and survival within the hippocampus. However,
      the links between perturbations in neurogenesis and genomic control remain
      unclear. Here, we examined the impact of mouse strain on four parameters of the
      neurogenic program, proliferation, migration, differentiation and survival in the
      dentate gyrus of the hippocampus as a means of determining whether allelic
      variation of two independently derived mouse strains, FVB/NJ and C57BL/6J,
      modulates basal adult murine dentate gyrus neurogenesis. New cells were labeled
      with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU) and their identity was
      determined immunocytochemically with various phenotypic markers. Consistent with
      previous studies in other strains of mice, we observed a strain-dependent
      difference in hippocampal proliferation. Hippocampal cell proliferation in FVB/NJ
      mice was reduced as compared to animals of the C57BL/6J strain. In contrast, the
      number of surviving cells in C57BL/6J mice was not significantly different from
      FVB/NJ mice. Regardless of mouse strain, the majority of surviving BrdU-labeled
      cells migrated into the granule cell layer and was of a neuronal phenotype.
      However, fewer surviving cells were located within the granule cell layer of
      FVB/NJ mice as compared to C57BL/6J mice. Overall, regardless of strain, no
      significant differences in the relative ratio of neurogenesis versus gliagenesis
      were observed. These results suggest that genetic background primarily influences
      newborn cell proliferation and migration, but not differentiation or survival.

PMID- 16999942
TI  - Is high-spatial frequency information used in the early stages of face detection?
AB  - The present study examined the role of high-spatial frequency information in
      early face processing, as indexed by the N170 face-sensitive ERP component.
      Participants detected 4 versions of famous faces, including full spectrum faces,
      and bandpass filtered faces containing predominantly high-spatial frequencies,
      low-spatial frequencies or both. The power spectra of all stimuli were balanced
      by superimposing the faces onto a visual noise background that included the
      spatial frequency information that was missing in filtered faces, e.g., high
      spatial frequency faces were presented on a high- and low-spatial frequency
      background. An additional condition comprising of filtered visual noise only was
      also created to ensure that any observed effects were related to the processing
      of faces and not simply due to variations between spatial frequency information.
      Both behavioral and electrophysiological results replicated previous findings of
      a low-spatial frequency advantage for face processing. However, our results also
      show that faces containing both high and low-spatial frequency information are
      detected faster and more accurately than faces containing predominantly low
      spatial frequencies. Furthermore, this advantage occurred with an enhanced
      amplitude of the N170. Together, these findings refute the suggestion that high
      spatial frequencies are redundant in face perception.

PMID- 16999943
TI  - Mortality patterns among industrial workers exposed to chloroprene and other
      substances. I. General mortality patterns.
AB  - We conducted an historical cohort study to investigate the mortality experience
      of industrial workers potentially exposed to chloroprene (CD) and other
      substances, including vinyl chloride (VC), with emphasis on cancer mortality,
      including respiratory system (RSC) and liver. In 1999, the International Agency
      for Research on Cancer (IARC) classified CD as a possible carcinogen (Group 2B);
      VC was classified in 1987 as a known human carcinogen (Group 1). Subjects were
      12,430 workers ever employed at one of two U.S. industrial sites (Louisville, KY
      (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown, Northern
      Ireland (n=4849) and Grenoble, France (n=717)), with earliest CD production dates
      ranging from 1942 (L) to 1969 (P). Two sites (L and M) synthesized CD with the
      acetylene process that produced VC exposures. We determined vital status through
      2000 for 95% of subjects and cause of death for 95% of the deaths. Historical
      exposures for individual workers were estimated quantitatively for CD and VC.
      Workers ever exposed to CD ranged from 92.3% (M) to 100% (G); to VC from 5.5% (M)
      to 22.7% (L). We computed standardized mortality ratios (SMRs) (using national
      and regional standard populations) in relation to selected demographic, work
      history and exposure factors. We used worker pay type (white or blue collar) as a
      rough surrogate for lifetime smoking history. For the combined cohort, SMRs (95%
      CIs) for all causes combined, all cancers combined, RSC and liver cancer were,
      respectively, 0.72 (0.69-0.74), 0.73 (0.68-0.78), 0.75 (0.67-0.84) and 0.72 (0.43
      1.13). Site-specific (L, M, P and G, respectively) SMRs were: for all cancers
      combined: 0.75 (0.69-0.80), 0.68 (0.56-0.80), 0.68 (0.47-0.95) and 0.59 (0.36
      0.91); for RSC: 0.75 (0.66-0.85), 0.79 (0.58-1.05), 0.62 (0.32-1.09) and 0.85
      (0.41-1.56); for liver cancer: 0.90 (0.53-1.44) (17 deaths), 0.24 (0.01-1.34) (1
      death), 0.0 (0-2.39) (no deaths) and 0.56 (0.01-3.12) (1 death). Among all
      workers ever exposed to CD, SMRs were: for all cancers combined: 0.71 (0.66
      0.76); for RSC: 0.75 (0.67-0.84); for liver cancer: 0.71 (0.42-1.14). We also
      observed no increased mortality risks among cohort subgroups defined by race,
      gender, worker pay type, worker service type (short/long term), time period, year
      of hire, age at hire, duration of employment, the time since first employment,
      and CD or VC exposure status (never/ever exposed). In summary, our study has many
      strengths and is the most definitive study of the human carcinogenic potential of
      exposure to CD conducted to date. We conclude that persons exposed to chloroprene
      or vinyl chloride at the levels encountered in the four study sites did not have
      elevated risks of mortality from any of the causes of death examined, including
      all cancers combined and lung and liver cancer, the cancer sites of a priori
      interest. This conclusion is corroborated by our detailed analyses of mortality
      in relation to qualitative and quantitative exposures to CD and VC at each of the
      four study sites, reported in our companion paper (Marsh et al., submitted for
      publication).

PMID- 16999944
TI  - Low concentrations mono-butyl phthalate stimulates steroidogenesis by
      facilitating steroidogenic acute regulatory protein expression in mouse Leydig
      tumor cells (MLTC-1).
AB  - Di-n-butyl phthalate (DBP) is one of the most dominant phthalate esters and is
      widely distributed environmental contaminant. Although previous studies have
      demonstrated that DBP led to a variety of male reproductive abnormalities similar
      to those caused by androgen receptor antagonists, DBP and its active metabolite,
      mono-butyl phthalate (MBP), have been demonstrated no affinity for the androgen
      receptor, but rather exert anti-androgenic effect by altering testosterone
      biosynthesis. Furthermore, all these results were obtained from very high
      administrations of DBP or MBP. The purpose of this study was to determine the
      onset and the site of action of relatively low concentration of MBP on
      steroidogenesis in vitro. The mouse Leydig tumor cells (MLTC-1) was employed as a
      cellular model to investigate the effect of MBP on steroidogenesis. Various
      concentrations of MBP (1, 10, 100 and 1000nmol/l) and its solvent dimethyl
      sulfoxide (DMSO) were added to the medium for 24h followed by stimulation of some
      compounds such as human chorionic gonadotrophin (hCG), cholera toxin (CT),
      forskolin, cAMP analog 8-Br-cAMP, 22(R)-hydroxycholesterol (22R-HC) and
      pregnenolone. Progesterone in the medium and amounts of intracellular cAMP were
      measured by RIA. Expression of steroidogenic acute regulatory protein (StAR) was
      monitored by real-time PCR and Western blotting. The results revealed that the
      increases of progesterone production in the presence of hCG, CT, forskolin and 8
      Br-cAMP were augmented by MBP. In contrast, the levels of intracellular cAMP
      exhibited no statistical significance when MLTC-1 cells were treated as above.
      These results implied that the site in the steroid biosynthesis pathway affected
      by MBP occurs after PKA activation in MLTC-1 cells. Moreover, supplementing the
      medium with 22R-HC and pregnenolone as progesterone precursors for P450 side
      chain cleavage enzyme (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta
      HSD), respectively, resulted in no rise in progesterone production, making clear
      that MBP did not influence the P450scc and 3beta-HSD but on the rate-limiting
      step, cholesterol transportation into mitochondria. In fact, the above results
      were confirmed by the upgraded StAR expression in MBP-treated cells. These data
      support that MBP promotes steroid hormone production by facilitating StAR
      expression in MLTC-1 cells.

PMID- 16999945
TI  - Accumulation and metabolism of the anticancer flavonoid 5,7-dimethoxyflavone
      compared to its unmethylated analog chrysin in the Atlantic killifish.
AB  - The use of dietary flavonoids as potential chemopreventive agents is a concept of
      increasing interest. Recent findings indicate that methylated flavones have the
      advantage of increased metabolic stability. One such compound, the naturally
      occurring 5,7-dimethoxyflavone (5,7-DMF), has been shown to be a potential
      chemopreventive agent in human cancer originating from the liver, mouth,
      esophagus and lung. As bioavailability is a key issue for potential in vivo
      effects, the tissue accumulation and biliary elimination of 5,7-DMF and its non
      methylated analog chrysin were examined in a small fish model (Fundulus
      heteroclitus). The fish were exposed to 5,7-DMF, chrysin or vehicle control
      (DMSO<0.01%) in seawater for 8h. Toxicity was not observed at the 5microM
      exposure level. Tissues and bile were harvested and analyzed by HPLC and LC/MS
      for quantitation and identification of parent compound and metabolites. 5,7-DMF
      accumulated 20-fold to 100-fold in all tissues examined, with the highest
      accumulation in liver and brain, whereas chrysin was barely detectable in any
      tissues except the liver. The bile of chrysin-exposed fish contained very low
      concentrations of unchanged chrysin but high concentrations of two glucuronic
      acid conjugates. In the bile of 5,7-DMF-exposed fish, the parent compound was
      detectable in significant amounts along with glucuronic acid conjugates of O
      demethylated 5,7-DMF. In conclusion, our study demonstrated high tissue
      accumulation and limited metabolism of 5,7-DMF compared to chrysin in vivo,
      making this flavone a promising chemopreventive molecule.

PMID- 16999946
TI  - Reduction of C-reactive protein by a single 80 mg of simvastatin in patients with
      unstable angina.
AB  - BACKGROUND: Increased concentrations of C-reactive protein (CRP) became widely
      accepted as a risk factor of the higher incidence of coronary events, and rapid
      lowering CRP by administration of drugs may produce early benefit to the coronary
      endothelium in patients with coronary heart disease and reduce angina and
      coronary events after revascularization. Limited information has been available,
      however, with respect to evaluating a potential effect of a single high-dose
      simvastatin on CRP in patients with unstable angina (UA) within 48 h. We
      investigated whether a rapid CRP reduction can be achieved by a single 80 mg of
      simvastatin therapy in patients with UA given immediately on admission. METHODS:
      Forty-two patients with rest chest pain were randomly assigned to a single
      placebo or 80 mg of simvastatin given at the time of admission plus standard
      therapy. Blood samples were also drawn at the time of admission, and 48 h later
      for measuring serum CRP concentrations. RESULTS: We found that 80 mg of
      simvastatin induced significant reductions in serum median CRP concentrations and
      in mean CRP concentrations 48 h later following administration of simvastatin
      (25.4% and 32.7%, p<0.001, respectively). CONCLUSIONS: A single high-dose
      simvastatin, given in the early time on admission, is an effective therapy for
      controlling inflammatory response in patients with UA, and the benefit to the
      vascular endothelium might occur quickly by reduction of CRP concentrations in
      this high-risk subgroup.

PMID- 16999947
TI  - Improved method for analysis of glycosaminoglycans in glycosaminoglycan/protein
      mixtures: application in Cohn-Oncley fractions of human plasma.
AB  - BACKGROUND: Glycosaminoglycans are found in human tissues including plasma. They
      encompass chondroitin sulphates, heparan sulphate/heparin, hyaluronic acid, and
      keratan sulphate. Glycosaminoglycans, in particular heparan sulphate and heparin,
      are strongly associated with plasma proteins, so that their purification results
      quite difficult. METHODS: In order to study the distribution of
      glycosaminoglycans in plasma subfractions, we developed a novel method that
      allows their identification even if they were still associated with proteins or
      peptides. Plasma was fractionated following the procedure of Cohn-Oncley, and
      each fraction was treated with proteases. After centrifugation,
      glycosaminoglycan/protein complexes in the supernatant were analysed using a
      modified cellulose acetate electrophoresis which allowed identification of
      glycosaminoglycans in mixtures of glycosaminoglycans/proteins. RESULTS:
      Chondroitin sulphate was recovered in cryoprecipitate and in all Cohn-Oncley
      fractions. Glycosaminoglycans belonging to the class of heparan sulphate/heparin,
      however, were recovered in the cryoprecipitate and in fractions I and IV-1, and,
      in smaller amount, in fraction II+III. CONCLUSIONS: Since the largest amount of
      plasma proteins is partitioned in Factions II+III and V, these results
      demonstrate that heparan sulphate/heparin are not randomly distributed in Cohn
      Oncley fractions and are associated with certain plasma proteins. This
      association might play a role in the physiological function of heparan
      sulphate/heparin, regulating hemostasis and atherogenesis.

PMID- 16999948
TI  - Individual single tube genotyping and DNA pooling by allele-specific PCR to
      uncover associations of polymorphisms with complex diseases.
AB  - BACKGROUND: The genotyping for the study of the SNPs in different complex
      diseases require a great number of patients. In this sense, the determination of
      allele frequencies and genotypes requires a rapid and economical procedure.
      METHODS: The genotype has been carried out by allele-specific PCR in single tube
      with the discrimination of the products of PCR by its T(m). For this purpose a GC
      tail was added to 5' extreme of the specific primer. The allele frequencies were
      also calculated by DNA pooling and QRT-PCR using allele-specific primers.
      RESULTS: The use of the genotyping in single tube through allele-specific PCR and
      melting curves has led us to the accurate genotype of three polymorphisms of vdr
      (cdx-2), osteoprotegerin (A-163G) and ppar-gamma (C-681G) genes in 225
      postmenopausal women to be associated to osteoporosis. Only the cdx-2
      polymorphism was associated with a reduced bone mineral density (BMD). These data
      were similar to those obtained when the allele frequencies were calculated using
      QRT-PCR in DNA pools. CONCLUSIONS: Individual genotyping with allele-specific PCR
      in single tube and melting curve analysis is a fast, trustworthy and economic
      method to study any SNP. We propose the following approach to determine the
      possible association of SNPs with complex and multifactorial diseases like
      osteoporosis, in which hundreds of individuals should be analyzed: construct
      control and problem groups, make DNA pools, and calculate pooled allelic
      frequencies. Genotyping each individual further permits to determine the
      genotypic distribution when differences in allelic frequencies are observed, thus
      allowing more complex statistical analyses (including other variables like age,
      weight, etc.).

PMID- 16999949
TI  - Serum prolidase activity and oxidative status in Helicobacter pylori infection.
AB  - OBJECTIVES: During the course of Helicobacter pylori infection, increased
      oxidative stress plays an important role in the pathogenesis of gastroduodenal
      mucosal inflammation, which can cause gastric mucosal atrophy that characterized
      by the replacement of the gastric mucosal glands by collagen fibers. In the
      present study, we aimed to determine serum prolidase activity and oxidative
      status, and to find out if there is any association between serum prolidase
      activity and oxidative status in H. pylori infection. DESIGN AND METHODS: Forty
      H. pylori-positive and 32 H. pylori-negative subjects were enrolled. Serum
      prolidase activity was measured spectrophotometrically. Oxidative status was
      determined using total antioxidant capacity and total oxidant status measurement
      and calculation of oxidative stress index. RESULTS: Total antioxidant capacity
      level was lower in H. pylori-positive group than H. pylori-negative group
      (p<0.001), whereas total oxidant status, oxidative stress index and prolidase
      activity were higher (all p<0.05). Significant correlation was observed between
      serum prolidase activity, and total antioxidant capacity, total oxidant status
      and oxidative stress index (p<0.01, r=-0.367; p<0.05, r=0.283; p<0.01, r=0.379;
      respectively) in H. pylori-positive subjects. CONCLUSION: H. pylori infection may
      be associated with increased oxidative stress and increased serum prolidase
      activity. Increased oxidative stress seems to be associated with increased serum
      prolidase activity and this association may help to provide a better
      understanding about the pathogenesis of H. pylori infection.

PMID- 16999950
TI  - The effect of atorvastatin therapy on lecithin:cholesterol acyltransferase,
      cholesteryl ester transfer protein and the antioxidant paraoxonase.
AB  - OBJECTIVES: The aim of our study was to examine the influence of atorvastatin on
      lipid parameters, particularly on HDL, and on the activity of LCAT and CETP and
      how they affect the activity of the HDL-associated antioxidant enzyme
      paraoxonase. DESIGN AND METHODS: Thirty-three patients with types II.a and II.b
      primary hyperlipoproteinemia were enrolled into our study. The patients received
      atorvastatin, 20 mg daily, for 3 months. We measured the serum paraoxonase
      activity and concentration, oxidized LDL, LCAT and CETP activities. RESULTS:
      Atorvastatin significantly reduced the levels of cholesterol, triglyceride, LDL-C
      and apoB, while it did not influence the levels of HDL-C and apo A-I. The
      increases in serum PON-specific activity, PON/HDL ratio and LCAT activity were
      significant, while oxLDL and CETP activities were significantly decreased.
      CONCLUSION: Atorvastatin may influence the composition and function of HDL,
      thereby possibly increasing the activity of paraoxonase and preventing
      atherosclerosis.

PMID- 16999951
TI  - HO-1 and VGEF gene expression in human arteries with advanced atherosclerosis.
AB  - OBJECTIVES: Both heme oxygenase-1 (HO-1) and vascular endothelial growth factor
      (VEGF) have been shown to be involved in the progression of atherosclerosis. The
      relationship between HO-1 and VEGF gene expression and their proteins in
      endothelial cells from human atherosclerotic arterial specimens was investigated.
      DESIGN AND METHODS: The study included seventeen human arterial specimens with
      early and six specimens with advanced atherosclerotic lesions. Ten specimens were
      obtained from healthy young adults undergoing arterial reconstruction for trauma
      and were considered as non-atherosclerotic control. HO-1 and VEGF expressions as
      well as HO activity and VEGF protein content were measured in isolated
      endothelial cells (ECs). RESULTS: HO-1 expression and activity (5.3+/-2.1 nmol
      bilirubin/mg protein/h) were only present in ECs from advanced atherosclerotic
      lesions. VEGF expression was more strongly expressed in ECs from advanced lesion
      compared with early lesions and was absent in healthy arteries. VEGF protein
      (1.35+/-0.69 ng/mg) was only detected in advanced lesions. A significant positive
      correlation (r=0.9, p<0.01) exists between HO activity and VEGF protein content
      in ECs of advanced lesions. CONCLUSIONS: This study demonstrated that HO-1
      expression and activity in ECs are present only in advanced atherosclerosis
      whereas, VEGF expression is present in early as well as in advanced
      atherosclerosis and the degree of its expression increases with severity of
      atherosclerosis. This study suggests an association between HO activity and VEGF
      protein in human ECs from advanced atherosclerotic lesions.

PMID- 16999952
TI  - Improved early stroke detection: wavelet-based perception enhancement of
      computerized tomography exams.
AB  - Nonenhanced computerized tomography (CT) exams were used to detect acute stroke
      by notification of hypodense area. Infarction perception improvement by data
      denoising and local contrast enhancement in multi-scale domain was proposed. The
      wavelet-based image processing method enhanced the subtlest signs of hypodensity,
      which were often invisible in standard CT scan review. Thus improved detection
      efficiency of perceptual ischemic changes was investigated. Data processing
      became more effective by initial segmentation of brain tissue and extraction of
      regions susceptible to tissue density changes. The new method was experimentally
      verified. Sensitivity of stroke diagnosis increased to 56.3% in comparison to
      12.5% of standard CT scan preview.

PMID- 16999953
TI  - Global analysis of hematopoietic and vascular endothelial gene expression by
      tissue specific microarray profiling in zebrafish.
AB  - In this study, we utilize fluorescent activated cell sorting (FACS) of cells from
      transgenic zebrafish coupled with microarray analysis to globally analyze
      expression of cell type specific genes. We find that it is possible to isolate
      cell populations from Tg(fli1:egfp)(y1) zebrafish embryos that are enriched in
      vascular, hematopoietic and pharyngeal arch cell types. Microarray analysis of
      GFP+ versus GFP- cells isolated from Tg(fli1:egfp)(y1) embryos identifies genes
      expressed in hematopoietic, vascular and pharyngeal arch tissue, consistent with
      the expression of the fli1:egfp transgene in these cell types. Comparison of
      expression profiles from GFP+ cells isolated from embryos at two different time
      points reveals that genes expressed in different fli1+ cell types display
      distinct temporal expression profiles. We also demonstrate the utility of this
      approach for gene discovery by identifying numerous previously uncharacterized
      genes that we find are expressed in fli1:egfp-positive cells, including new
      markers of blood, endothelial and pharyngeal arch cell types. In parallel, we
      have developed a database to allow easy access to both our microarray and in situ
      results. Our results demonstrate that this is a robust approach for
      identification of cell type specific genes as well as for global analysis of cell
      type specific gene expression in zebrafish embryos.

PMID- 16999955
TI  - VIP is a transcriptional target of Nurr1 in dopaminergic cells.
AB  - The orphan nuclear receptor Nurr1 is required for the development of the ventral
      mesencephalic dopaminergic neurons. These are the same neurons that are
      invariantly lost in patients with Parkinson's disease. Nurr1 mRNA expression is
      not confined to the developing midbrain, and yet Nurr1 appears to be essential
      for either the maturation of progenitors into fully post-mitotic dopaminergic
      neurons and/or once formed, their survival. The function of Nurr1 in the
      transactivation of gene(s) important for neuronal development and/or maintenance
      is uncharacterized. To characterize potential downstream target genes of Nurr1,
      we sought to identify mRNAs that are differentially affected by Nurr1 expression.
      Using a dopaminergic cell line in which Nurr1 content was tightly regulated,
      differential display analysis identified transcripts altered by Nurr1 expression,
      including the mRNA encoding vasoactive intestinal peptide (VIP). Herein, we
      demonstrate that Nurr1 regulates VIP mRNA and protein levels, and transactivates
      the VIP promoter through Nurr1-responsive cis elements. In addition, dopaminergic
      cells release and utilize VIP to mediate survival when challenged with paraquat.
      Nurr1 regulation of VIP is also demonstrated in vivo as loss of Nurr1 function
      results in diminished VIP mRNA levels within the developing midbrain.

PMID- 16999956
TI  - Assessment of ovarian reserve by using the follicle-stimulating hormone isoform
      distribution pattern to predict the outcome of in vitro fertilization.
AB  - Changes in FSH isoforms occur at temporally specific times during the menstrual
      cycle and reproductive lifespan. Changes in ratio in FSH isoforms may provide a
      sensitive test of ovarian reserve before IVF.

PMID- 16999957
TI  - Isolation and expression analysis of multiple isoforms of putative farnesoic acid
      O-methyltransferase in several crustacean species.
AB  - Farnesoic acid O-methyltransferase (FaMeT) is the enzyme responsible for the
      conversion of farnesoic acid (FA) to methyl farnesoate (MF) in the final step of
      MF synthesis. Multiple isoforms of putative FaMeT were isolated from six
      crustacean species belonging to the families Portunidae, Penaeidae, Scyllaridae
      and Parastacidae. The portunid crabs Portunus pelagicus and Scylla serrata code
      for three forms: short, intermediate and long. Two isoforms (short and long) were
      isolated from the penaeid prawns Penaeus monodon and Fenneropenaeus merguiensis.
      Two isoforms were also identified in the scyllarid Thenus orientalis and
      parastacid Cherax quadricarinatus. Putative FaMeT sequences were also amplified
      from the genomic DNA of P. pelagicus and compared to the putative FaMeT
      transcripts expressed. Each putative FaMeT cDNA isoform was represented in the
      genomic DNA, indicative of a multi-gene family. Various tissues from P. pelagicus
      were individually screened for putative FaMeT expression using PCR and fragment
      analysis. Each tissue type expressed all three isoforms of putative FaMeT
      irrespective of sex or moult stage. Protein domain analysis revealed the presence
      of a deduced casein kinase II phosphorylation site present only in the long
      isoform of putative FaMeT.

PMID- 16999958
TI  - Effects of artificial social stimuli on the reproductive schedule and hormone
      levels of yellow-eyed penguins (Megadyptes antipodes).
AB  - The effects of social stimuli on avian reproductive behaviors such as breeding
      schedules and courtship behaviors are well known due to numerous field studies.
      However, studies that have simultaneously examined the effects of social stimuli
      on reproductive behavior and the mediating endocrine mechanisms have been largely
      restricted to captive populations, which may not be representative of free-living
      populations. This study, conducted over two breeding seasons, aimed to
      simultaneously measure the effects of experimentally increasing auditory stimuli
      on the breeding schedule and endocrinology (levels of total androgen, estradiol,
      progesterone and prolactin) on free-living yellow-eyed penguins (Megadyptes
      antipodes). The yellow-eyed penguin is the least colonial of all penguins,
      nesting far apart from each other under dense vegetation, and, therefore, is
      presumed to experience much lower levels of social stimuli than other penguins.
      Egg laying was significantly more synchronous and tended to be earlier when birds
      were exposed to playbacks of the calls of conspecifics in 1 year of the study. We
      also found that levels of total androgen and estradiol of males in 1 year, and
      prolactin in another year, were proportionally higher among treated birds
      compared control birds that received no artificial auditory stimuli. These
      results show that even among supposedly solitary nesters, social stimuli could
      still play a role in influencing reproductive behavior and physiology. For the
      first time in free-living seabirds, we have demonstrated that behavioral
      responses to increased social stimuli are associated with hormonal changes.

PMID- 16999959
TI  - Laser cylindrical excision for cervical adenocarcinoma in situ.

PMID- 16999960
TI  - Levonorgestrel-releasing intrauterine system vs. transcervical endometrial
      resection for dysfunctional uterine bleeding.
AB  - OBJECTIVE: To compare the acceptability, efficacy, adverse effects, and user
      satisfaction of a levonorgestrel intrauterine system (LNG-IUS) and transcervical
      resection of the endometrium (TCRE) for the treatment of dysfunctional uterine
      bleeding. METHOD: Of 50 women with a pictoral blood loss assessment chart (PBAC)
      score of 100 or greater, 25 had a LNG-IUS inserted (Mirena; Schering, Berlin,
      Germany) and 25 underwent TCRE. Procedure-related complications, PBAC score,
      hemoglobin levels, adverse effects, and rates of acceptability and satisfaction
      were recorded at 3-month intervals for a period of 12 months. RESULTS: At the end
      of 1 year there were a 97% and a 94% reduction in menstrual blood loss in the LNG
      IUS and TCRE groups, respectively, and hemoglobin concentration had increased by
      5.5% in the LNG-IUS group and 5.2% in the TCRE group. Adverse effects were
      similar in both groups except for systemic effects, which were seen only in the
      LNG-IUS group. Satisfaction rates were about 80% in the 2 groups. CONCLUSION:
      Both treatments were found to be equally effective but LNG-IUS placement requires
      less operator skill and entails no operative hazards, and the device provides
      effective contraception.

PMID- 16999961
TI  - Legal abortion for mental health indications.
AB  - Where legal systems allow therapeutic abortion to preserve women's mental health,
      practitioners often lack access to mental health professionals for making
      critical diagnoses or prognoses that pregnancy or childcare endangers patients'
      mental health. Practitioners themselves must then make clinical assessments of
      the impact on their patients of continued pregnancy or childcare. The law
      requires only that practitioners make assessments in good faith, and by credible
      criteria. Mental disorder includes psychological distress or mental suffering due
      to unwanted pregnancy and responsibility for childcare, or, for instance,
      anticipated serious fetal impairment. Account should be taken of factors that
      make patients vulnerable to distress, such as personal or family mental health
      history, factors that may precipitate mental distress, such as loss of personal
      relationships, and factors that may maintain distress, such as poor education and
      marginal social status. Some characteristics of patients may operate as both
      precipitating and maintaining factors, such as poverty and lack of social
      support.

PMID- 16999962
TI  - Ethical issues in transnational "mail order" oocyte donation.
AB  - The rising demand for donor oocytes in developed countries has led to what is
      referred to as transnational or international oocyte donation, or the outsourcing
      of oocyte donation to poorer countries. In a further twist, frozen sperm from a
      recipient's partner can also be mailed to a foreign clinic to fertilize donor
      oocytes, and the resulting embryos are mailed back, cryopreserved, for transfer
      to the recipient. Among the numerous ethical concerns raised by this practice of
      mail order oocyte donation, the most obvious are that underprivileged women from
      poorer countries are often exploited; fertility physicians from richer counties
      abdicate responsibility for the welfare of donors; and responsibility could
      become an issue of contention if transmission of disease to the oocyte recipient
      or congenital defects in offspring born from such oocyte donation were to occur.
      Moreover, savings from utilizing donors from poorer countries ought to be shared
      with oocyte recipients.

PMID- 16999964
TI  - Chromosomal and cardiac anomalies in fetuses with intracardiac echogenic foci.
AB  - OBJECTIVE: To evaluate the prevalence of intracardiac echogenic foci (ICEF) and
      the association between ICEF and chromosomal and cardiac anomalies in Brazilian
      women. METHODS: In a cross-sectional observational study, 373 of the 23,360
      genetic sonograms performed at a private maternal-fetal medicine clinic over 5
      years showed intracardiac echogenic foci (ICEF). These 373 sonograms were
      reviewed for chromosomal and cardiac anomalies and associations were analyzed
      using the chi(2) test or the Fisher exact test. P<0.05 was considered
      significant. RESULTS: The prevalence of ICEF was 1.7%. Cardiac anomalies were
      detected in 10 sonograms (2.7%) and chromosomal anomalies in 14 (3.7%). There
      were cardiac defects in 6 (1.7%) of the 359 euploid fetuses with isolated ICEF.
      Of the 373 women who had fetuses with ICEF, 295 were younger than 35 years and 78
      were 35 years or older. There were 6 fetuses (2.1%) with aneuploidy in the
      younger group and 8 (10.3%) in the older group. CONCLUSION: The prevalence of
      ICEF was 1.7%, and there was an association between cardiac and chromosomal
      anomalies. Women carrying fetuses with ICEF should be offered fetal
      echocardiography and karyotyping.

PMID- 16999965
TI  - Intracerebral hemorrhage in postpartum cerebral angiopathy associated with the
      use of isometheptene.

PMID- 16999966
TI  - Pulse oxygen saturation in healthy newborns at term in Cusco, Peru.

PMID- 16999967
TI  - Chemical stability of reversed phase high performance liquid chromatography
      silica under sodium hydroxide regeneration conditions.
AB  - Chromatographic sorbents used within the purification of peptide or protein based
      active pharmaceutical ingredients (APIs) are commonly subjected to caustic
      regeneration procedures, so-called CIP treatments. While polymeric materials
      remain unaffected by this treatment, silica-based sorbents are at an intrinsic
      risk of dissolution under high pH conditions, such as, e.g. 0.1M NaOH. It is
      common misconception that silica-based materials simply cannot be subjected to
      alkaline conditions above pH 9. Moreover, most studies covering the chemical
      stability of HPLC sorbents above pH 9 have been limited to the chromatographic
      conditions used for the separations themselves. Such studies have used buffered
      mobile phases up to pH 11 or 12. Very little focus has been put on the stability
      of the stationary phases when subjected to shorter but harsher pH conditions
      required for regeneration purposes, such as 0.1M NaOH (pH 13). Knowledge about
      the amount of so-called leachables, degradation products originating from the
      stationary phase, is of growing importance for the registration of
      pharmaceuticals for human use and is addressed in this work. This study compares
      the chemical stability of different commercially available reversed phase silica
      materials (C18) that are used in industrial scale preparative HPLC. The silica
      materials were subjected to NaOH regeneration conditions and it is shown that
      some materials are able to withstand 0.1M NaOH conditions without significant
      harm. It is demonstrated that contaminants present in the effluent in the range
      of 10-50 microg/mL can lead to significant contamination of API product fraction.

PMID- 16999968
TI  - Determination of oxygenated polycyclic aromatic hydrocarbons in particulate
      matter using high-performance liquid chromatography-tandem mass spectrometry.
AB  - A high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS)
      method with a rapid and simple sample preparation was optimized and validated for
      the determination of phenanthrene-9,10-dione, chrysene-5,6-dione, benzo[a]pyrene
      1,6-dione, benzo[a]pyrene-3,6-dione, benzo[a]pyrene-4,5-dione, benzo[a]pyrene
      6,12-dione, benzo[a]pyrene-7,8-dione, benzo[a]pyrene-11,12-dione and 6-oxo-7-oxa
      benzo[a]pyrene in particulate matter. The mass spectrometer was operated in the
      multiple reaction monitoring (MRM) mode leading to high sensitivity and
      selectivity. The limits of quantification (S/N=10) ranged from ca. 0.1 pg/microl
      to ca. 5.8 pg/microl and matrix dependent recoveries varied between 49 and 92%.
      The applicability of the LC-MS/MS method was shown by the analysis of particulate
      matter (PM(2.5)) collected during the course of 2005 in the Munich area, Germany.
      All oxy-PAHs determined exhibited higher mean and peak concentrations in the
      winter months compared to the concentration levels in the warmer season.

PMID- 16999969
TI  - Molecularly imprinted polymers for triazine herbicides prepared by multi-step
      swelling and polymerization method. Their application to the determination of
      methylthiotriazine herbicides in river water.
AB  - Uniformly-sized, molecularly imprinted polymers (MIPs) for atrazine, ametryn and
      irgarol were prepared by a multi-step swelling and polymerization method using
      ethylene glycol dimethacrylate as a cross-linker and methacrylic acid (MAA), 2
      (trifluoromethyl) acrylic acid (TFMAA) or 4-vinylpyridine either as a functional
      monomer or not. The MIP for atrazine prepared using MAA showed good molecular
      recognition abilities for chlorotriazine herbicides, while the MIPs for ametryn
      and irgarol prepared using TFMAA showed excellent molecular recognition abilities
      for methylthiotriazine herbicides. A restricted access media-molecularly
      imprinted polymer (RAM-MIP) for irgarol was prepared followed by in situ
      hydrophilic surface modification using glycerol dimethacrylate and glycerol
      monomethacrylate as hydrophilic monomers. The RAM-MIP was applied to selective
      pretreatment and enrichment of methylthiotriazine herbicides, simetryn, ametryn
      and prometryn, in river water, followed by their separation and UV detection via
      column-switching HPLC. The calibration graphs of these compounds showed good
      linearity in the range of 50-500 pg/mL (r > 0.999) with a 100 mL loading of a
      river water sample. The quantitation limits of simetryn, ametryn and prometryn
      were 50 pg/mL, and the detection limits were 25 pg/mL. The recoveries of
      simetryn, ametryn and prometryn at 50 pg/mL were 101%, 95.6% and 95.1%,
      respectively. This method was successfully applied for the simultaneous
      determination of simetryn, ametryn and prometryn in river water.

PMID- 16999970
TI  - Development of high-performance liquid chromatographic fingerprint for the
      quality control of Rheum tanguticum Maxim. ex Balf.
AB  - A novel, accurate and valid fingerprint method was developed by using high
      performance liquid chromatography-photodiode array detection (HPLC-DAD) to
      control the quality of Rheum tanguticum Maxim. ex Balf. By comprehensively
      comparing chromatograms of all samples, our result revealed that the
      chromatographic fingerprint we developed combining similarity evaluation could
      efficiently identify and distinguish raw materials of R. tanguticum from
      different sources. Besides, 21 characteristic peaks in chromatogram of R.
      tanguticum were unambiguously confirmed by comparison of reference compounds
      based on their retention time (t(R)) and UV spectra.

PMID- 16999971
TI  - Improved glucuronide hydrolysis in the determination of urinary 1-hydroxypyrene.
AB  - The efficiency of the glucuronide hydrolysis in the determination of urinary 1
      hydroxypyrene was investigated as a function of the reaction conditions. A
      significant improvement could be obtained by increasing the enzyme concentration
      described in the literature.

PMID- 16999972
TI  - Determination of chlorinated volatile organic compounds in water and municipal
      wastewater using headspace-solid phase microextraction-gas chromatography.
AB  - The aim of this work was to develop a fast and simple analytical method for the
      determination of 14 chlorinated volatile organic compounds (VOCs) in water and
      wastewater samples. Headspace-solid-phase microextraction (HS-SPME) and gas
      chromatography (GC) were used for the determination of the VOCs. The extraction
      parameters were investigated in order to optimize the HS-SPME-GC method. The
      quality parameters of the method were also investigated.

PMID- 16999973
TI  - Enantioseparation of palonosetron hydrochloride by micellar electrokinetic
      chromatography with sodium cholate as chiral selector.
AB  - The enantioseparation of four stereoisomers of palonosetron hydrochloride by
      micellar electrokinetic chromatography using sodium cholate as chiral surfactant
      was described. Sodium cholate was shown to be effective in separating
      palonosetron hydrochloride stereoisomers. For method optimization, several
      parameters such as sodium cholate concentration, buffer pH and concentration, the
      types and concentration of organic modifiers and applied voltage, on the
      enantioseparation were evaluated and the optimum conditions were obtained as
      follows: 30 mM borate buffer (pH 9.40) containing 70 mM sodium cholate and 20%
      (v/v) methanol with an applied voltage of 20 kV. Under these conditions, baseline
      separation of palonosetron hydrochloride stereoisomers was achieved within 18
      min.

PMID- 16999974
TI  - New screening method for basic compounds in urine by on-line extraction-high
      performance liquid chromatography with photodiode-array detection.
AB  - A fully automated, qualitative screening HPLC method for the identification of
      basic compounds in urine has been developed. A 1-ml volume of urine was extracted
      by on-line extraction and separated on two coupled strong cation-exchange (SCX)
      columns (2 x LunaSCX, 150 mm x 4.6 mm, 5 microm) under isocratic conditions. The
      mobile phase consisted of a mixture of potassium dihydrogenphosphate buffer (pH
      2.3) and acetonitrile. The use of photodiode-array detection (DAD, lambda = 190
      800 nm) gave access to a library of approximately 2600 toxicologically relevant
      compounds. The validated method is reliable, simple and in addition successfully
      proven with the analysis of real biological specimen for the routine use.

PMID- 16999975
TI  - Non-derivatized analysis of methiin and alliin in vegetables by capillary
      electrophoresis.
AB  - Methiin and alliin are important components of flavors or the precursors of
      flavors and odors of Allium vegetables. Moreover, they are thought to be
      beneficial to health. A non-derivative method was developed to analyze these
      compounds in vegetables by capillary electrophoresis. These compounds in the
      extracts of Allium and Brassica vegetables were detected indirectly at 225 nm.
      The analysis of each sample required less than 25 min, and the linear detection
      range was 5-5000 mg/l. This method was simple compared to the other published
      methods using high performance liquid chromatography. Moreover, it was possible
      to detect the peak of pyruvate simultaneously with methiin and alliin using this
      method. The presence of pyruvate peak is a useful indicator if the blanching of
      the samples has been insufficient.

PMID- 16999976
TI  - Solution NMR structure of the junction between tropomyosin molecules:
      implications for actin binding and regulation.
AB  - Tropomyosin is a coiled-coil protein that binds head-to-tail along the length of
      actin filaments in eukaryotic cells, stabilizing them and providing protection
      from severing proteins. Tropomyosin cooperatively regulates actin's interaction
      with myosin and mediates the Ca2+ -dependent regulation of contraction by
      troponin in striated muscles. The N-terminal and C-terminal ends are critical
      functional determinants that form an "overlap complex". Here we report the
      solution NMR structure of an overlap complex formed of model peptides. In the
      complex, the chains of the C-terminal coiled coil spread apart to allow insertion
      of 11 residues of the N-terminal coiled coil into the resulting cleft. The plane
      of the N-terminal coiled coil is rotated 90 degrees relative to the plane of the
      C terminus. A consequence of the geometry is that the orientation of postulated
      periodic actin binding sites on the coiled-coil surface is retained from one
      molecule to the next along the actin filament when the overlap complex is modeled
      into the X-ray structure of tropomyosin determined at 7 Angstroms. Nuclear
      relaxation NMR data reveal flexibility of the junction, which may function to
      optimize binding along the helical actin filament and to allow mobility of
      tropomyosin on the filament surface as it switches between regulatory states.

PMID- 16999977
TI  - IGF-1 protects intestinal epithelial cells from oxidative stress-induced
      apoptosis.
AB  - BACKGROUND: Reactive oxygen species (ROS) are involved in the pathogenesis of
      necrotizing enterocolitis (NEC) in premature infants. We have recently found that
      activation of multiple cellular signaling transduction pathways occurs during ROS
      induced intestinal cell apoptosis; the phosphatidylinositol 3-kinase (PI3-K)
      pathway plays an anti-apoptotic role during this process. Insulin-like growth
      factor (IGF)-1 activates PI3-K pathway to promote cell survival; however, the
      effects of IGF-1 treatment during gut injury are not clearly defined. The purpose
      of this study was to determine whether IGF-1 protects intestinal cells from ROS
      induced apoptosis. MATERIALS AND METHODS: Rat intestinal epithelial (RIE)-1 cells
      were treated with either IGF-1 (100 nm), hydrogen peroxide (H2O2; 500 microm), or
      combination. Western blotting was performed to assess phosphorylation of Akt, a
      downstream effector of PI3-K. Cell Death Detection ELISA, DCHF, and JC-1 assays
      were performed to demonstrate protective effects of IGF-1. Wortmannin, an
      inhibitor of PI3-K, was used to show PI3-K-dependent mechanism of action for IGF
      1. RESULTS: H2O2 treatment resulted in increased intestinal epithelial cell
      apoptosis with intracellular ROS generation and mitochondrial membrane
      depolarization; IGF-1 pre-treatment attenuated this response without affecting
      ROS production. H2O2-induced phosphorylation of Akt was further increased with
      IGF-1 treatment; wortmannin abolished these effects in RIE-1 cells. CONCLUSIONS:
      PI3-K pathway is activated during ROS-induced intestinal epithelial cell injury;
      IGF-1 exerted an anti-apoptotic effect during this response by PI3-K activation.
      A better understanding of the exact role of IGF-1-mediated activation of PI3-K
      may allow us to facilitate the development of novel therapy against NEC.

PMID- 16999978
TI  - Home anticoagulation testing: predictors of rural patient interest.
AB  - BACKGROUND: Home anticoagulation testing (HAT) may be useful for rural patients
      who cannot attend an anticoagulation service clinic (ASC). Interest in HAT is
      unknown and was the focus of this study. MATERIALS AND METHODS: Anticoagulated
      patients from two clinics, the ASC and vascular surgery clinic (VSC) were
      surveyed and compared for demographics, anticoagulation knowledge and opinions,
      and HAT interest. Logistic regression was performed, using the entire patient
      cohort, to identify factors associated with HAT interest. RESULTS: There were 211
      (141 ASC, 70 VSC) patients surveyed. Differences between the ASC and VSC patients
      included education level (13.2 versus 12.1 years; P = 0.02), time spent testing
      (60.5 +/- 33.5 versus 46.4 +/- 20.7 min; P = 0.001), use of fingerstick testing
      (90% versus 2.9%; P < 0.001), and knowledge of the potential interaction of
      warfarin with medications or diet (79% versus 59% P = 0.003). HAT interest was
      similar (62.1% ASC versus 50% VSC; P = 0.14). Factors associated with HAT
      interest included employment [odds ratio (OR) 2.9, 95% confidence interval (CI)
      1.2-6.7], knowledge of potential interactions between medications and warfarin
      (OR 3.9, 95% CI 1.9-8.1), and a willingness to check international normalized
      ratio values more frequently if recommended (OR 2.4, 95% CI 1.2-4.6). Patients
      who received family help with medications appeared less interested in HAT (OR
      0.29, 95% CI 0.12-0.68). CONCLUSIONS: A slight majority of surveyed rural
      patients conveyed interest in HAT. Working patients and those assuming more
      responsibility for international normalized ratio control may be more interested
      in HAT. A possible association between anticoagulation knowledge and increased
      HAT interest was seen and should be further studied.

PMID- 16999980
TI  - Sex determines the neurofunctional predictors of visual word learning.
AB  - This study used functional MRI and an artificial language training paradigm to
      explore sex differences in the processing of a new writing system and how sex
      determines the optimal neural resource recruitment for visual word learning.
      Results indicated that males and females achieved equal learning outcome, and
      their learning curve followed a similar power function. They also showed similar
      overall activation in the fusiform cortex, a region that has been associated with
      visual word processing. Despite the absence of sex differences in averaged
      behavioral performance and neural activation, males and females were found to
      have different neural predictors of visual word learning. As predicted, left
      lateralized fusiform activation predicted visual word learning for males, but not
      for females, whereas bilateral fusiform activation predicted visual word learning
      for females, but not males. These results suggest that male and female brains
      operate differently to achieve the best performance in visual word learning. The
      individual-differences approach adopted in the present study provides a new and
      useful perspective to sex differences.

PMID- 16999979
TI  - Inhibition of spontaneous mutagenesis by vanillin and cinnamaldehyde in
      Escherichia coli: Dependence on recombinational repair.
AB  - Vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutagens that effectively
      inhibit both induced and spontaneous mutations. We have shown previously that VAN
      and CIN reduced the spontaneous mutant frequency in Salmonella TA104 (hisG428,
      rfa, DeltauvrB, pKM101) by approximately 50% and that both compounds
      significantly reduced mutations at GC sites but not at AT sites. Previous studies
      have suggested that VAN and CIN may reduce mutations in bacterial model systems
      by modulating DNA repair pathways, particularly by enhancing recombinational
      repair. To further explore the basis for inhibition of spontaneous mutation by
      VAN and CIN, we have determined the effects of these compounds on survival and
      mutant frequency in five Escherichia coli strains derived from the wild-type
      strain NR9102 with different DNA repair backgrounds. At nontoxic doses, both VAN
      and CIN significantly reduced mutant frequency in the wild-type strain NR9102, in
      the nucleotide excision repair-deficient strain NR11634 (uvrB), and in the
      recombination-proficient but SOS-deficient strain NR11475 (recA430). In contrast,
      in the recombination-deficient and SOS-deficient strain NR11317 (recA56), both
      VAN and CIN not only failed to inhibit the spontaneous mutant frequency but
      actually increased the mutant frequency. In the mismatch repair-defective strain
      NR9319 (mutL), only CIN was antimutagenic. Our results show that the
      antimutagenicity of VAN and CIN against spontaneous mutation required the RecA
      recombination function but was independent of the SOS and nucleotide excision
      repair pathways. Thus, we propose the counterintuitive notion that these
      antimutagens actually produce a type of DNA damage that elicits recombinational
      repair (but not mismatch, SOS, or nucleotide excision repair), which then repairs
      not only the damage induced by VAN and CIN but also other DNA damage-resulting in
      an antimutagenic effect on spontaneous mutation.

PMID- 16999981
TI  - Things that go bump in the right: the effect of unimanual activity on rightward
      collisions.
AB  - Patients with right parietal damage and spatial neglect ignore the leftward
      features of their environment - causing them to bump into the left-side of
      doorways. In contrast, the normal population shows a mild attentional bias
      towards the left. Self-report measures show more collisions to the right in
      everyday settings. We sought to obtain a quantitative measure of lateralised
      bumping in a laboratory setting. Participants (n=276) walked through a narrow
      doorway and the experimenter recorded collisions. To investigate the association
      between bumping and paper-and-pencil tests of pseudoneglect, a line bisection
      task was administered. Unilateral activation of the hemispheres has been found to
      ameliorate the effects of spatial neglect. We investigated the effect of
      activation by asking participants to move their left-, right- or both-hands as
      they walked. In the both hands condition, which acted as a baseline, there were
      more right bumps than left bumps. The rightward bias was exasperated when the
      left hand moved, presumably because this movement activated the right hemisphere.
      In contrast, there were more left bumps when the right hand moved. The results
      demonstrate that bumping is not random and that we collide with the right side
      more often. Biases in bumping, however, were not related to biases in line
      bisection. The effect of hand-movement demonstrates that bumping is brought about
      by an imbalance of activation between the hemispheres.

PMID- 16999982
TI  - The good, the bad and the ugly: Australian snake taxonomists and a history of the
      taxonomy of Australia's venomous snakes.
AB  - The Australian snake fauna is unique in harbouring more venomous species than non
      venomous ones. Although taxonomic research on the elapid snakes of Australia goes
      back to the late 18th century, in stark contrast to other developed regions of
      the world (e.g. the continental USA), Australian snake taxonomy is very much in
      its infancy. Despite this, or perhaps because of this, the taxonomy of Australian
      snakes has been extraordinarily controversial, and many of the taxonomists
      involved correspondingly colourful. In this review, we explore the sometimes
      tortured history of the taxonomic exploration of the venomous snake fauna of
      Australia, looking at some of the more colourful and notable contributors and
      highlighting systematic pitfalls that persist even today.

PMID- 16999983
TI  - The envelope gene is a cytopathic determinant of CCR5 tropic HIV-1.
AB  - Late stage AIDS associated CCR5 tropic HIV-1 clones (R5-AIDS HIV-1) exhibit
      greater cytopathic effects (CPE) than earlier isolates from the same patients. In
      this study, envelopes from a series of three biological clones derived from the
      same patient were evaluated as a cytopathic determinant of R5-AIDS HIV-1 for
      thymocytes. In a single round of replication in thymocytes, the AIDS associated
      clone mediated greater initiation of reverse transcription. This enhancement was
      not due to broadened coreceptor tropism, as all clones studied were exclusively
      R5 tropic. The full-length R5-AIDS env mediated greater infectivity than R5 pre
      AIDS env when used to pseudotype a reporter virus. R5-AIDS env pseudotypes were
      more resistant to TAK-779 and showed more rapid infection kinetics but similar
      resistance to a CD4 blocking mAb. We conclude that the enhanced thymic
      replication and CPE shown by the R5-AIDS clone is due to enhanced efficiency of
      Env-mediated entry via CCR5.

PMID- 16999984
TI  - Analysis of the roles of E6 binding to E6TP1 and nuclear localization in the
      human papillomavirus type 31 life cycle.
AB  - The E6 oncoproteins of high-risk human papillomaviruses provide important
      functions not only for malignant transformation but also in the productive viral
      life cycle. E6 proteins have been shown to bind to a number of cellular factors,
      but only a limited number of analyses have investigated the effects of these
      interactions on the viral life cycle. In this study, we investigated the
      consequences of HPV 31 E6 binding to E6TP1, a putative Rap1 GAP protein. HPV 16
      E6 has been shown to bind as well as induce the rapid turnover of E6TP1, and
      similar effects were observed with HPV 31 E6. Mutation of amino acid 128 in HPV
      31 E6 was found to abrogate the ability to bind and degrade E6TP1 but did not
      alter binding to another alpha-helical domain protein, E6AP. When HPV 31 genomes
      containing mutations at amino acid 128 were transfected into human keratinocytes,
      the viral DNAs were not stably maintained as episomes indicating the importance
      of this residue for pathogenesis. Many E6 binding partners including E6TP1 are
      cytoplasmic proteins, but E6 has been also reported to be localized to the
      nucleus. We therefore investigated the importance of E6 localization to the
      nucleus in the viral life cycle. Using a fusion of E6 to Green Fluorescent
      Protein, we mapped one component of the nuclear localization sequences to
      residues 121 to 124 of HPV 31 E6. Mutation of these residues in the context of
      the HPV 31 genome abrogated the ability for episomes to be stably maintained and
      impaired the ability to extend the life span of cells. These studies identify two
      activities of HPV 31 E6 that are important for its function in the viral life
      cycle and for extension of cell life span.

PMID- 16999985
TI  - Variation in enamel development of South African fossil hominids.
AB  - Dental tissues provide important insights into aspects of hominid palaeobiology
      that are otherwise difficult to obtain from studies of the bony skeleton. Tooth
      enamel is formed by ameloblasts, which demonstrate daily secretory rhythms
      developing tissue-specific structures known as cross striations, and longer
      period markings called striae of Retzius. These enamel features were studied in
      the molars of two well known South African hominid species, Australopithecus
      africanus and Paranthropus robustus. Using newly developed portable confocal
      microscopy, we have obtained cross striation periodicities (number of cross
      striations between adjacent striae) for the largest sample of hominid teeth
      reported to date. These data indicate a mean periodicity of seven days in these
      small-bodied hominids. Important differences were observed in the inferred
      mechanisms of enamel development between these taxa. Ameloblasts maintain high
      rates of differentiation throughout cervical enamel development in P. robustus
      but not in A. africanus. In our sample, there were fewer lateral striae of
      Retzius in P. robustus than in A. africanus. In a molar of P. robustus, lateral
      enamel formed in a much shorter time than cuspal enamel, and the opposite was
      observed in two molars of A. africanus. In spite of the greater occlusal area and
      enamel thickness of the molars of both fossil species compared with modern
      humans, the total crown formation time of these three fossil molars was shorter
      than the corresponding tooth type in modern humans. Our results provide support
      for previous conclusions that molar crown formation time was short in Plio
      Pleistocene hominids, and strongly suggest the presence of different mechanisms
      of amelogenesis, and thus tooth development, in these taxa.

PMID- 16999986
TI  - Protective role of aminoguanidine on gentamicin-induced acute renal failure in
      rats.
AB  - The toxicity of aminoglycosides including gentamicin (GEN), the most widely used
      drug in this category, is believed to be related to the generation of reactive
      oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective
      antioxidant and its free radical scavenger effects may protect GEN-induced acute
      renal failure (ARF). Therefore, this study was focused on investigating the
      possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo
      rat model. We investigated the effects of AG on GEN-induced changes in renal
      tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione
      peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities;
      glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN)
      levels. Morphological changes in the kidney were also examined using light
      microscopy. GEN administration to control group rats increased renal MDA and NO
      levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG
      administration with GEN injection resulted in significantly decreased MDA, NO
      generation and increased GSH-Px, SOD, CAT activities and GSH content when
      compared with GEN alone. Serum levels of Cr and BUN significantly increased as a
      result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels.
      Morphological changes in the kidney, including tubular necrosis, intracellular
      edema, glomerular and basement membrane alterations were evaluated qualitatively.
      Both biochemical findings and histopathological evidence showed that
      administration of AG reduced the GEN-induced kidney damage. We propose that AG
      acts in the kidney as a potent scavenger of free radicals to prevent the toxic
      effects of GEN both at the biochemical and histological level.

PMID- 16999987
TI  - Ernst Wynder: a remembrance.
AB  - Ernst Wynder, founder and president of the American Health Foundation, was my
      employer, mentor, and colleague for nearly 25 years. This brief remembrance
      provides some experiences and perspectives that influenced my career as a cancer
      epidemiologist.

PMID- 16999988
TI  - Selection of developmentally competent oocytes through brilliant cresyl blue
      stain enhances blastocyst development rate after bovine nuclear transfer.
AB  - The aim of the present investigation was to study the effect of oocyte selection
      on the efficiency of bovine nuclear transfer in terms of increased blastocyst
      production. For this purpose, prior to in vitro maturation (IVM), oocytes were
      selected for their developmental competence on the basis of glucose-6-phosphate
      dehydrogenase (G6PDH) activity indicated by brilliant cresyl blue (BCB) staining.
      It has been hypothesized that growing oocytes have a higher level of active G6PDH
      in comparison to the mature oocytes. Compact cumulus oocyte complexes (COCs) were
      recovered from slaughterhouse-collected bovine ovaries and classified either as
      control group, which were placed immediately into culture without exposure to BCB
      stain, or treatment group, which were stained with BCB for 90min before culture.
      Treated oocytes were then divided into BCB- (colourless cytoplasm, increased
      G6PDH) and BCB+ (coloured cytoplasm, low G6PDH) based on their ability to
      metabolize the stain. After IVM, oocytes were subjected to nuclear transfer
      procedure for the production of cloned embryos which were then cultured for a
      period of 8 days to determine the blastocyst rate. The BCB+ oocytes yielded a
      significantly higher blastocyst rate (39%) than the control (21%) or BCB- oocytes
      (4%). These results show that the staining of bovine cumulus-oocyte complexes
      with BCB before in vitro maturation could be used to select developmentally
      competent oocytes for nuclear transfer. In addition, G6PDH activity could prove
      to be a useful marker for determining the oocyte quality in future.

PMID- 16999989
TI  - A study of syntactic processing in aphasia I: behavioral (psycholinguistic)
      aspects.
AB  - This paper presents the results of a study of syntactically based comprehension
      in aphasic patients. We studied 42 patients with aphasia secondary to left
      hemisphere strokes and 25 control participants. We measured off-line, end-of
      sentence, performance (accuracy and reaction time) in two tasks that require
      comprehension--enactment and sentence-picture matching--and in grammaticality
      judgment, with whole sentence auditory presentation. We also used sentence
      picture matching and grammaticality judgment as tasks in two self-paced listening
      studies with the same patients to measure on-line performance. In each task and
      presentation format, we presented sentences that tested the ability to assign and
      interpret three structural contrasts chosen to examine different basic syntactic
      operations: actives and passives, subject and object extracted relative clauses,
      and reflexive pronouns and matched sentences without these elements. We examined
      these behavioral data to determine patterns of impairment in individual patients
      and in groups of patients, using correlational analyses, factor analyses, and
      analyses of variance. The results showed that almost no individual patients had
      stable deficits referable to the ability to interpret individual syntactic
      structures, that a variety of structural features contributed to sentence
      processing complexity both on-line and off-line, that correct responses were
      associated with normal on-line and errors with abnormal performance, and that the
      major determinant of performance is a factor that affected performance on all
      sentence types. The results indicate that the major cause of aphasic impairments
      of syntactically based comprehension are intermittent reductions in the
      processing capacity available for syntactic, interpretive, and task-related
      operations.

PMID- 16999990
TI  - Frequency of stuttering during challenging and supportive virtual reality job
      interviews.
AB  - This paper seeks to demonstrate the possibility of manipulating the frequency of
      stuttering using virtual reality environments (VREs). If stuttering manifests
      itself in VREs similarly to the way it manifests itself in real world
      interactions, then VREs can provide a controlled, safe, and confidential method
      for treatment practice and generalization. Though many researchers and clinicians
      recognize the need for generalization activities in the treatment of stuttering,
      achieving generalization in a clinical setting poses challenges to client
      confidentiality, safety, and the efficient use of a professionals' time. Virtual
      reality (VR) technology may allow professionals the opportunity to enhance and
      assess treatment generalization while protecting the safety and confidentiality
      of their clients. In this study, we developed a VR job interview environment
      which allowed experimental control over communication style and gender of
      interviewers. In this first trial, persons who stutter (PWS) experienced both
      challenging and supportive VR job interview conditions. The percentage of
      stuttered syllables was calculated for both interviews for each participant. Self
      reported ratings of communication apprehension and confidence were also obtained,
      and were not significantly correlated with stuttering severity. Results indicated
      that interviewer communication style affected the amount of stuttering produced
      by participants, with more stuttering observed during challenging virtual
      interviews. Additionally, the amount of stuttering observed during the VR job
      interviews was significantly, positively correlated with the amount of stuttering
      observed during an interview with the investigator prior to VR exposure.
      Participants' subjective reports of the VR experience indicate reactions similar
      to those they report experiencing in the real world. Possible implications for
      the use of VR in the assessment and treatment of stuttering are discussed.
      EDUCATIONAL OBJECTIVES: After reading this article, the reader will be able to
      (1) list some of the challenges to treatment generalization; (2) describe how
      virtual reality technology can assist in alleviating some of these challenges;
      (3) describe how the frequency of stuttering varies across two different virtual
      environments.

PMID- 16999991
TI  - Neuronal macroautophagy: from development to degeneration.
AB  - Macroautophagy, a lysosomal pathway responsible for the turnover of organelles
      and long-lived proteins, has been regarded mainly as an inducible process in
      neurons, which is mobilized in states of stress and injury. New studies show,
      however, that macroautophagy is also constitutively active in healthy neurons and
      is vital to cell survival. Neurons in the brain, unlike cells in the periphery,
      are protected from large-scale autophagy induction because they can use several
      different energy sources optimally, receive additional nutrients and neurotrophin
      support from glial cells, and benefit from hypothalamic regulation of peripheral
      nutrient supplies. Due to its exceptional efficiency, constitutive autophagy in
      healthy neurons proceeds in the absence of easily detectable autophagic vacuole
      intermediates. These intermediates can accumulate rapidly, however, when late
      steps in the autophagic process are blocked. Autophagic vacuoles also accumulate
      abnormally in affected neurons of several major neurodegenerative diseases,
      including Alzheimer's disease and Parkinson's disease, where they have been
      linked to various aspects of disease pathogenesis including neuronal cell death.
      The build-up of autophagic vacuoles in these neurological disorders and others
      may reflect either heightened autophagy induction, impairment in later digestive
      steps in the autophagy pathway, or both. Determining the basis for AV
      accumulation is critical for understanding the pathogenic significance of
      autophagy in a given pathologic state and for designing possible therapies based
      on modulating autophagy. In this review, we discuss the special features of
      autophagy regulation in the brain, its suspected roles in neurodevelopment and
      plasticity, and recent progress toward understanding how dysfunctional autophagy
      contributes to neurodegenerative disease.

PMID- 16999992
TI  - Nutrient control of macroautophagy in mammalian cells.
AB  - A growing number of evidences indicate a strict causality between the reduction
      of autophagic functionality and aging. In this context the preservation of a
      proper autophagic response is of paramount importance to preserve the cellular
      processes in aging cell. Nutrients availability, especially for amino acids, is
      the most physiological key regulator of macroautophagy. In mammalian cells the
      knowledge of the mechanism and the underlying regulation of macroautophagy has
      been greatly improved in recent years and we focus on the role of nutrients, in
      particular on their involvement in preventing cellular aging through the
      modulation of autophagy. This review covers the main features of macroautophagy
      regulation by nutrients, in particular amino acids as well as glucose and
      vitamins, and its mechanisms, focusing primarily on the mammalian hepatocyte,
      which has been extensively utilized to dissect signaling pathways underlying the
      regulation of macroautophagy.

PMID- 16999993
TI  - Spin-labelling study of interactions of ovalbumin with multilamellar liposomes
      and specific anti-ovalbumin antibodies.
AB  - Ovalbumin (OVA) has been used continuously as the model antigen in numerous
      studies of immune reactions and antigen processing, very often encapsulated into
      liposomes. The purpose of this work was to study the possible interactions of
      spin-labelled OVA and lipids in liposomal membranes using electron spin resonance
      (ESR) spectroscopy. OVA was covalently spin-labelled with 4-maleimido-2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO-maleimide), characterized and encapsulated
      into multilamellar, negatively charged liposomes. ESR spectra of this liposomal
      preparation gave evidence for the interaction of OVA with the lipid bilayers.
      Such an interaction was also evidenced by the ESR spectra of liposomal
      preparation containing OVA, where liposomes were spin-labelled with n-doxyl
      stearic acids. The spin-labelled OVA retains its property to bind specific anti
      OVA antibodies, as shown by ESR spectroscopy, but also in ELISA for specific anti
      OVA IgG.

PMID- 16999994
TI  - Three-dimensional (3-D) imaging of chondrocytes in articular cartilage: growth
      associated changes in cell organization.
AB  - Three-dimensional (3-D) imaging and analysis techniques can be used to assess the
      organization of cells in biological tissues, providing key insights into the role
      of cell arrangement in growth, homeostasis, and degeneration. The objective of
      the present study was to use such methods to assess the growth-related changes in
      cell organization of articular cartilage from different sites in the bovine knee.
      Three-dimensional images of fetal, calf, and adult cartilage were obtained and
      processed to identify cell nuclei. The density of cells was lower with growth and
      with increasing depth from the articular surface. The cell organization, assessed
      by the angle to the nearest neighboring cell, also varied with growth, and
      reflected the classical organization of cells in adult tissue, with neighboring
      cells arranged horizontally in the superficial zone (average angle of 20 degrees)
      and vertically in the deep zone (60 degrees). In all other regions and growth
      stages of cartilage, the angle was approximately 32 degrees, indicative of an
      isotropic organization. On the contrary, the nearest neighbor distance did not
      vary significantly with growth or depth. Together, these results indicate that
      cartilage growth is associated with distinctive 3-D arrangements of groups of
      chondrocytes.

PMID- 16999995
TI  - Synthesis and characterization of chitosan-g-poly(ethylene glycol)-folate as a
      non-viral carrier for tumor-targeted gene delivery.
AB  - Poor water solubility and low transfection efficiency of chitosan are major
      drawbacks for its use as a gene delivery carrier. PEGylation can increase its
      solubility, and folate conjugation may improve gene transfection efficiency due
      to promoted uptake of folate receptor-bearing tumor cells. The aim of this study
      was to synthesize and characterize folate-poly(ethylene glycol)-grafted chitosan
      (FA-PEG-Chi) for targeted plasmid DNA delivery to tumor cells. Gel
      electrophoresis study showed strong DNA binding ability of modified chitosan. The
      pH(50) values, defined as the pH when the transmittance of a polymer solution at
      600 nm has reached 50% of the original value, suggested that the water solubility
      of PEGylated chitosan had improved significantly. Regression analysis of pH(50)
      value as a function of substitution degree of PEG yielded an almost linear
      correlation for PEG-Chi and FA-PEG-Chi. The solubility of PEGylated chitosan
      decreased slightly by further conjugation of folic acid due to the relatively
      more hydrophobic nature of folic acid when compared to PEG. In addition, the
      chitosan-based DNA complexes did not induce remarkable cytotoxicity against HEK
      293 cells. FA-PEG-Chi can be a promising gene carrier due to its solubility in
      physiological pH, efficiency in condensing DNA, low cytotoxicity and targeting
      ability.

PMID- 16999996
TI  - Free and bound intracellular calmodulin measurements in cardiac myocytes.
AB  - Calmodulin (CaM) is a ubiquitous Ca2+ binding protein and Ca2+-CaM activates many
      cellular targets and functions. While much of CaM is thought to be protein bound,
      quantitative data in cardiac myocytes is lacking regarding CaM location,
      [CaM]free and CaM redistribution during changes in [Ca2+]i. Here, we demonstrated
      that in adult rabbit cardiac myocytes, CaM is highly concentrated at Z-lines
      (confirmed by Di-8-ANEPPS staining of transverse tubules) using three different
      approaches: immunocytochemistry (endogenous CaM), Alexa Fluor 488 conjugate CaM
      (F-CaM) in both permeabilized cells (exogenous CaM) and in patch clamped intact
      cells (via pipette dialysis). Using 100 nM [CaM]free we washed F-CaM into
      permeabilized myocytes and saw a two-phase (fast and slow) CaM binding curve with
      a plateau after 40 min of F-CaM wash-in. We also measured myocyte [CaM]free using
      two modified null-point titration methods, finding [CaM]free to be 50-75 nM
      (which is only 1% of total [CaM]). Higher [Ca2+]i increased CaM binding
      especially in the nucleus and at Z-lines and significantly slowed F-CaM
      dissociation rate when F-CaM was washed out of permeabilized myocytes.
      Additionally, in both permeabilized and intact myocytes, CaM moved into the
      nucleus when [Ca2+]i was elevated, and this was reversible. We conclude that
      [CaM]free is very low in myocytes even at resting [Ca2+]i, indicating intense
      competition of CaM targets for free CaM. Bound CaM is relatively concentrated at
      Z-lines at rest but translocates significantly to the nucleus upon elevation of
      [Ca2+]i, which may influence activation of different targets and cellular
      functions.

PMID- 16999997
TI  - Altered Ca2+ handling of smooth muscle cells in aorta of apolipoprotein E
      deficient mice before development of atherosclerotic lesions.
AB  - To study the effect of hypercholesterolemia on vascular smooth muscle cell (VSMC)
      function, atherosclerosis-prone but plaque-free endothelium-denuded aortic rings
      (width 2mm) from C57Bl6 Wild Type (WT) and apolipoprotein E-deficient (apoE(-/-))
      mice (age 4 months) were mounted in a myograph and loaded with Fura-2 AM to
      simultaneously measure free Ca(2+) ([Ca(2+)](i)) and force development. In
      comparison with WT, apoE(-/-) mice displayed higher basal [Ca(2+)](i). Moreover,
      the time constant of the second phase of the biphasic high K(+)-induced
      [Ca(2+)](i) response was significantly increased in apoE(-/-) compared to WT
      mice. This phase was abolished by treatment with cyclopiazonic acid (CPA),
      depleting sarcoplasmic reticulum (SR). Further investigation of SR dependent
      [Ca(2+)](i) handling with CPA and caffeine revealed no alteration of maximal
      SERCA or ryanodine receptor function. Inositol (1,4,5)-triphosphate receptor
      (IP(3)R)-mediated [Ca(2+)](i) release was, however, significantly increased in
      apoE(-/-) mice compared to WT mice as established with phenylephrine and ATP. In
      Ca(2+)-free conditions the ATP-induced [Ca(2+)](i) was not altered. The ATP
      induced store-operated Ca(2+) entry was, however, significantly increased in
      apoE(-/-) compared to WT mice. The results demonstrate that basal [Ca(2+)](i)
      levels and IP(3)R-mediated store-operated [Ca(2+)](i) release over the plasma
      membrane were elevated in hypercholesterolemic but plaque-free apoE(-/-) mice.

PMID- 16999998
TI  - Therapeutic responses in childhood acute lymphoblastic leukemia (ALL) and
      haplotypes of gamma glutamyl hydrolase (GGH) gene.

PMID- 16999999
TI  - Histone H2A as a transfection agent in crayfish hematopoietic tissue cells.
AB  - We report a novel and highly efficient dsRNA transfection system based on one of
      the nuclear proteins, namely, histone H2A. RT-PCR semi-quantitative analysis of
      silencing target gene shows that the transfection efficiency of histone H2A is
      higher than Effectene or liposome-based transfection systems. Importantly, the
      high efficiency of histone H2A was associated with very low toxicity to the
      transfected crayfish hematopoietic tissue (Hpt) cells. The non-toxicity,
      effectiveness and specificity of histone H2A as a transfection agent provides a
      cheap, simple, highly efficient and reproducible gene delivery system,
      particularly for the sensitive cell cultures of crustacean animals such as
      crayfish and shrimp.

PMID- 17000000
TI  - Genetic analysis of the complement factor H related 5 gene in haemolytic uraemic
      syndrome.
AB  - Several mutations in the CFH gene have been described in non-Shiga-toxin
      associated haemolytic uraemic syndrome (non-Stx-HUS), a rare syndrome
      characterized by haemolytic anaemia, thrombocytopenia and acute renal failure.
      Mutations in genes encoding other complement regulatory proteins, membrane
      cofactor protein (CD46) and complement factor I (CFI), were also involved in the
      pathogenesis of the disease. Anyway, mutations in the three genes account for no
      more than 50% of cases of non-Stx-HUS. Human complement factor H related 5
      (CFHR5) is a recently characterised member of the human complement factor H (CFH)
      family that has been found as a component of immune deposits in human kidney with
      sclerotic lesions from different causes. CFHR5 possesses cofactor activity and
      has been proposed to play a role in complement regulation in the glomerulus. We
      screened CFHR5 gene for variations potentially involved in the aetiology of HUS.
      Forty-five patients with HUS and 80 controls were analysed. Altogether, 5 genetic
      variants in CFHR5 were found in overall 9/45 HUS patients and in 4/80 controls.
      Statistical analysis showed that allelic variants in CFHR5 were prefentially
      associated with HUS. Based on these data, we conclude that, though not causative,
      CFHR5 genetic alterations may play a secondary role in the pathogenesis of HUS.

PMID- 17000001
TI  - An apparent paradox: chemokine receptor agonists can be used for anti
      inflammatory therapy.
AB  - Inflammation plays an important role in a wide range of human diseases.
      Chemokines are a group of proteins which control the migration and activation of
      the immune cells involved in all aspects of the inflammatory response. Chemokines
      bind to specific receptors of the seven-transmembrane spanning type on target
      leukocytes and also bind to cell-surface glycosaminoglycans (GAG). Leukocytes
      express a range of chemokine receptors which can cross-desensitise each other,
      potentially allowing a single chemokine receptor agonist to desensitise all the
      chemokine receptors on a cell. If an appropriate single receptor agonist is
      engineered to be non-chemotactic itself, then a treated cell will lose the
      potential to migrate in response to chemokines towards any developing site of
      inflammation. A non-GAG-binding but receptor agonistic form of the chemokine CCL7
      can inhibit leukocyte recruitment in response to a diverse range of chemokines in
      vitro and in vivo. We hypothesise that this modified chemokine mediates its
      effect by inducing homologous and heterologous receptor desensitisation and
      further propose that other suitable candidates could include agonistic chemokine
      receptor-specific antibodies or small molecule chemokine receptor agonists.
      Hence, an appropriate chemokine receptor agonist could be used to inhibit
      multiple chemokine receptors, thereby producing a powerful and robust anti
      inflammatory effect. This review considers the mechanisms leading to chemokine
      receptor desensitisation and discusses the potential to develop a new class of
      anti-inflammatory agents based on targeted stimulation of chemokine receptors.

PMID- 17000002
TI  - A humanized monoclonal antibody against interleukin-2 that can inactivate the
      cytokine/receptor complex.
AB  - Inhibition of the interleukin-2 (IL-2) pathway has potent immunosuppressive
      activity in humans as is evident from the broad therapeutic utility of
      cyclosporine, rapamycin, tacrolimus, and monoclonal antibodies blocking the high
      affinity subunit of the IL-2 receptor (CD25). Here we describe a humanized
      antibody, MT204, interfering with IL-2 signaling by a novel mechanism. Although
      MT204 did not prevent IL-2 from binding to CD25, it potently antagonized
      downstream signaling events of IL-2 at sub-nanomolar concentrations, such as
      STAT3 tyrosine phosphorylation, expression of CD124, production of gamma
      interferon and cell proliferation. While MT204 and the anti-CD25 mAb daclizumab
      were equally effective in inhibiting autocrine growth of human CD4(+) T cells,
      MT204 was far superior in preventing proliferation of NKL lymphoma cells,
      production of gamma-interferon by natural killer (NK) cells and proliferation of
      primary NK cells. MT204 has potential as a novel immunosuppressive and anti
      proliferative therapy with an apparently broader spectrum of activities than anti
      CD25 antibodies.

PMID- 17000003
TI  - Comment on: Acute cytomegalovirus infection and venous thrombosis: role of
      antiphospholipid antibodies.

PMID- 17000004
TI  - Mycobacterium bovis-mediated induction of human beta-defensin-2 in epithelial
      cells is controlled by intracellular calcium and p38MAPK.
AB  - Induction of human beta defensin-2 (HBD-2) by mycobacteria has been reported.
      However, the molecular mechanism(s) by which mycobacteria up-regulates HBD-2 gene
      expression in epithelial cells remains poorly understood. In this work, we
      provide evidence that the induction of HBD-2 mRNA in response to Mycobacterium
      bovis bacillus Calmette-Guerin (BCG) was inhibited in a dose-dependent manner by
      pretreatment with a cell-permeable BAPTA-AM, which chelates intracellular
      calcium. Our data also demonstrate that HBD-2 mRNA induction by M. bovis in A549
      lung epithelial cells requires activation of calmodulin. Interestingly, HBD-2
      mRNA expression in response to M. bovis BCG was attenuated by pretreatment with
      SB203580 (an inhibitor of p38 mitogen-activated protein kinase [MAPK]), but not
      by an inhibitor of extracellular signal-regulated kinase (ERK): PD98059.
      Furthermore, we found that a second p38 MAPK inhibitor (SB202190) significantly
      blocked M. bovis BCG-mediated HBD-2 induction in A549 lung epithelial cells.
      Together, these data suggest that M. bovis BCG induces HBD-2 mRNA expression in
      A549 lung epithelial cells at least in part mediated through intracellular
      calcium flux as well as activation of signaling protein of p38MAPK, but not ERK.

PMID- 17000005
TI  - Immunoglobulin E: role in asthma and allergic disease: lessons from the clinic.
AB  - The role of immunoglobulin E (IgE) in allergic asthmatic disease is well
      established. Allergen-specific IgE binds to its cognate receptors, thus
      triggering a series of cellular events. These events include presentation of
      antigen by dendritic cells and the degranulation of mast cells and basophils to
      release numerous factors that play an integral part in potentiating the disease
      symptoms. Studies in the mouse indicate that a reduction in IgE levels could lead
      to significant attenuation of the allergic inflammatory response associated with
      diseases such as asthma, making IgE a target for the development of new
      therapeutic agents. Omalizumab (Xolair), a recombinant humanised monoclonal anti
      IgE antibody that blocks the interaction of IgE with its receptors, is the first
      anti-IgE agent to undergo clinical development. Several clinical studies have
      been performed in adults and children with moderate-to-severe allergic asthma to
      evaluate the efficacy and safety of this agent, but which have also enabled an
      insight into the role of IgE in human disease. IgE plays a significant role in a
      number of allergic conditions including allergic rhinitis and allergies to
      various substances. Recent data suggests that local IgE production may occur in
      mucosal tissues and that locally significant concentrations of IgE, not reflected
      by serum IgE concentrations, indicate that it may play a role in non-atopic as
      well as atopic disease.

PMID- 17000006
TI  - Ion conducting polymer microelectrodes for interfacing with neural networks.
AB  - We have examined the stimulation and recording properties of conjugated polymer
      microelectrode arrays as interfaces with neural networks of dissociated cortical
      cells. In particular the stimulation properties were investigated as a means of
      supplying a neural network with information. The stimulation efficiency at low
      stimulation voltages was evaluated and referenced to bare indium tin oxide (ITO)
      electrodes. The polymer electrodes were electrochemically polymerized from a
      blend of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) and
      ethylenedioxythiophene (EDOT) onto ITO microelectrodes. Dissociated cortical
      cells were then plated on the electrodes and cultivated to form neural networks.
      Polymer electrode stimulation evoked a much greater response from the network
      than stimulation from ITO electrodes. Neural interfaces using polymer electrodes
      could be maintained for several months.

PMID- 17000007
TI  - Trial-by-trial estimation of amplitude and latency variability in neuronal spike
      trains.
AB  - The rate function underlying single-trial spike trains can vary from trial to
      trial. We propose to estimate the amplitude and latency variability in single
      trial neuronal spike trains on a trial-by-trial basis. The firing rate over a
      trial is modeled by a family of rate profiles with trial-invariant waveform and
      trial-dependent amplitude scaling factors and latency shifts. Using a Bayesian
      inference framework we derive an iterative fixed-point algorithm from which the
      single-trial amplitude scaling factors and latency shifts are estimated. We test
      the performance of the algorithm on simulated data and then apply it to actual
      neuronal recordings from the sensorimotor cortex of the monkey.

PMID- 17000008
TI  - Semiconductor ultra-violet light-emitting diodes for flash photolysis.
AB  - 'Caged' compounds are biological molecules that are rendered inactive by a
      protecting (cage) group. Photocleaving of chemical bonds associated with the cage
      species with intense UV light results in the release of the active molecules.
      This technique, called flash photolysis, allows for real-time study of
      interacting biological molecules and typically involves the use of high intensity
      lasers or flash lamps to deliver the UV pulse to the biological specimen
      [Callaway EM, Katz LC. Photostimulation using caged glutamate reveals functional
      circuitry in living brain slices. Proc Natl Acad Sci USA 1993;90(16):7661-5;
      Parpura V, Haydon PG. "Uncaging" using optical fibers to deliver UV light
      directly to the sample. Croat Med J 1999;40(3):340-5; Denk W. Pulsing mercury arc
      lamps for uncaging and fast imaging. J Neurosci Methods 1997;72(1):39-42]. Here,
      we introduce compact, custom-designed semiconductor UV light-emitting diodes
      (LEDs) as a viable and efficient source for performing flash photolysis studies,
      focusing specifically on the application of these devices for uncaging
      neurotransmitters locally onto neurons cultured on artificial substrates. The
      illumination design feature incorporated in these devices allows for direct
      placement of the UV source in immediate proximity with the neuron of interest and
      provides a means for optical triggering of activity in the neuronal culture.

PMID- 17000009
TI  - Polymorphism in the serotonin transporter gene and moderators of prolactin
      response to meta-chlorophenylpiperazine in African-American cocaine abusers and
      controls.
AB  - Serotonin (5-HT) function is altered in several psychiatric disorders, including
      cocaine dependence (CD), and its role in impulsive-aggressive behaviors has been
      widely studied. However, the relationship between psychopathological and
      behavioral dimensions and mechanisms of 5-HT alterations remains unclear. We
      investigated the relationship of a polymorphism in the 5' promoter region of the
      serotonin transporter gene (5-HTTLPR) with prolactin (PRL) response to meta
      chlorophenylpiperazine (m-CPP) in a sample of 68 African-American individuals, 35
      CD subjects and 33 controls. We also examined whether measures of impulsivity,
      hostility and sensation seeking influenced the relationship between the 5-HTTLPR
      polymorphism and PRL response to m-CPP in this sample. Individuals with the SS
      genotype showed significantly heightened PRL response to the challenge compared
      with the LL and LS genotypes. No influence of gender or substance abuse condition
      was observed. Hostility was associated with blunted PRL response in the total
      sample. Cocaine abuse was the most significant moderator of DeltaPRL (peak PRL
      baseline PRL), and the interaction of genetic, behavioral and psychopathological
      measures helped predict most of the observed DeltaPRL (62.5%). Although these
      results need replication, variation in the 5-HTTLPR gene appears to influence
      measures of 5-HT function and interact with disease state and personality
      dimensions to account for 5-HT disturbances in African-American populations.

PMID- 17000010
TI  - The missing link: chemokine receptors and tissue matrix breakdown in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a pulmonary inflammatory disease
      that is caused by cigarette smoke. The main characteristic of COPD is the
      continued inflammation caused by the sustained influx of macrophages and
      neutrophils into the lung. Recent studies have shed light on how these cells are
      attracted during acute and chronic inflammation of the lung. The factors involved
      might be both a biomarker and a therapeutic target in COPD.

PMID- 17000011
TI  - How important is protein kinase C in mu-opioid receptor desensitization and
      morphine tolerance?
AB  - The repeated administration of opiate drugs such as morphine results in the
      development of tolerance to their analgesic, rewarding (euphoric) and respiratory
      depressant effects; thus, to obtain the same level of response with subsequent
      administrations, a greater dose must be used. Tolerance can limit the clinical
      efficacy of opiate drugs and enhance the social problems that are inherent in
      recreational opioid abuse. Surprisingly, the mechanism (or mechanisms) underlying
      the development of morphine tolerance remains controversial. Here, we propose
      that protein kinase C could have a crucial role in the desensitization of mu
      opioid receptors by morphine and that this cellular process could contribute to
      the development and maintenance of morphine tolerance in vivo.

PMID- 17000012
TI  - Rapid detection, serotyping and quantitation of dengue viruses by TaqMan real
      time one-step RT-PCR.
AB  - The use of the polymerase chain reaction (PCR) in molecular diagnosis is now
      accepted worldwide and has become an essential tool in the research laboratory.
      In the laboratory, a rapid detection, serotyping and quantitation, one-step real
      time RT-PCR assay was developed for dengue virus using TaqMan probes. In this
      assay, a set of forward and reverse primers were designed targeting the serotype
      conserved region at the NS5 gene, at the same time flanking a variable region for
      all four serotypes which were used to design the serotype-specific TaqMan probes.
      This multiplex one-step RT-PCR assay was evaluated using 376 samples collected
      during the year 2003. These groups included RNA from prototype dengue virus (1
      4), RNA from acute serum from which dengue virus was isolated, RNA from tissue
      culture supernatants of dengue virus isolated, RNA from seronegative acute
      samples (which were culture and IgM negative) and RNA from samples of dengue IgM
      positive sera. The specificity of this assay was also evaluated using a panel of
      sera which were positive for other common tropical disease agents including
      herpes simplex virus, cytomegalovirus, measles virus, varicella-zoster virus,
      rubella virus, mumps virus, WWF, West Nile virus, Japanese encephalitis virus, S.
      typhi, Legionella, Leptospira, Chlamydia, and Mycoplasma. The sensitivity,
      specificity and real-time PCR efficiency of this assay were 89.54%, 100% and
      91.5%, respectively.

PMID- 17000013
TI  - Lipoprotein receptors in Alzheimer's disease.
AB  - Lipoprotein receptors have important roles in pathological processes that lead to
      Alzheimer's disease (AD). Previously, they were believed to act mainly by
      modulating the neuronal metabolism of cholesterol and apolipoprotein E, major
      risk factors for spontaneous AD. However, recent findings point towards an
      unexpected new function for lipoprotein receptors in regulation of intracellular
      transport and processing of the amyloid precursor protein (APP) to give amyloid
      beta peptide, the principal component of senile plaques. Here, we will discuss
      how lipoprotein receptors might modulate distinct steps in neuronal trafficking
      of APP, and how an intricate balance between opposing receptor activities might
      be a crucial determinant of APP processing, and of onset and progression of
      neurodegeneration.

PMID- 17000014
TI  - Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal
      stress responses.
AB  - Diets rich in vegetables and fruits are associated with reduced risk of several
      major diseases, including neurodegenerative disorders. Although some beneficial
      phytochemicals might function solely as antioxidants, it is becoming clear that
      many of the beneficial chemicals in vegetables and fruits evolved as toxins (to
      dissuade insects and other predators) that, at subtoxic doses, activate adaptive
      cellular stress-response pathways in a variety of cells including neurons.
      Examples of such 'preconditioning' or 'neurohormesis' pathways include those
      involving cell-survival signaling kinases, the transcription factors NRF2 and
      CREB, and histone deacetylases of the sirtuin family. In these ways,
      neurohormetic phytochemicals such as resveratrol, sulforaphanes and curcumin
      might protect neurons against injury and disease by stimulating the production of
      antioxidant enzymes, neurotrophic factors, protein chaperones and other proteins
      that help cells to withstand stress. Thus, as we discuss in this review, highly
      conserved longevity and survival pathways in neurons are the targets of many
      phytochemicals.

PMID- 17000015
TI  - Sex differences in oxytocin and vasopressin: implications for autism spectrum
      disorders?
AB  - Autism spectrum disorders (ASD) are male-biased and characterized by deficits in
      social behavior and social communication, excessive anxiety or hyperreactivity to
      stressful experiences, and a tendency toward repetitiveness. The purpose of this
      review is to consider evidence for a role for two sexually dimorphic
      neuropeptides, oxytocin (OT) and arginine vasopressin (VP), in these features of
      ASD. Both VP and OT play a role in normal development. VP is androgen-dependent
      and of particular importance to male behavior. Excess VP or disruptions in the VP
      system could contribute to the male vulnerability to ASD. Alternatively,
      protective processes mediated via OT or the OT receptor might help to explain the
      relatively rare occurrence of ASD in females. Disruptions in either OT or VP or
      their receptors could result from genetic variation or epigenetic modifications
      of gene expression, especially during early development. Deficits in other
      developmental growth factors, such as reelin, which may in turn regulate or be
      regulated by OT or VP, are additional candidates for a role in ASD.

PMID- 17000016
TI  - Dopamine transporter and D2 receptor binding densities in mice prone or resistant
      to chronic high fat diet-induced obesity.
AB  - This study examined the density of dopamine transporter (DAT) and D2 receptors in
      the brains of chronic high-fat diet-induced obese (cDIO), obese-resistant (cDR)
      and low-fat-fed (LF) control mice. Significantly decreased DAT densities were
      observed in cDR mice compared to cDIO and LF mice, primarily in the nucleus
      accumbens, striatal and hypothalamic regions. D2 receptor density was
      significantly lower in the rostral part of caudate putamen in cDIO mice compared
      to cDR and LF mice.

PMID- 17000017
TI  - Harnessing phage and ribosome display for antibody optimisation.
AB  - Therapeutic antibodies have become a major driving force for the
      biopharmaceutical industry; therefore, the discovery and development of safe and
      efficacious antibody leads have become competitive processes. Phage and ribosome
      display are ideal tools for the generation of such molecules and have already
      delivered an approved drug as well as a multitude of clinical candidates. Because
      they are capable of searching billions of antibody variants in tailored
      combinatorial libraries, they are particularly applicable to potency
      optimisation. In conjunction with targeted, random or semi-rational mutagenesis
      strategies, they deliver large panels of potent antibody leads. This review
      introduces the two technologies, compares them with respect to their use in
      antibody optimisation and highlights how they can be exploited for the successful
      and efficient generation of putative drug candidates.

PMID- 17000018
TI  - Just a phase they're going through: the complex interaction of intrinsic high
      threshold bursting and gap junctions in the generation of thalamic alpha and
      theta rhythms.
AB  - Rhythms in the alpha frequency band (8-13 Hz) are a defining feature of the human
      EEG during relaxed wakefulness and are known to be influenced by the thalamus. In
      the early stages of sleep and in several neurological and psychiatric conditions
      alpha rhythms are replaced by slower activity in the theta (3-7 Hz) band. Of
      particular interest is how these alpha and theta rhythms are generated at the
      cellular level. Recently we identified a subset of thalamocortical (TC) neurons
      in the lateral geniculate nucleus (LGN) which exhibit rhythmic high-threshold (>
      55 mV) bursting at approximately 2-13 Hz and which are interconnected by gap
      junctions (GJs). These cells combine to generate a locally synchronized continuum
      of alpha and theta oscillations, thus providing direct evidence that the thalamus
      can act as an independent pacemaker of alpha and theta rhythms. Interestingly, GJ
      coupled pairs of TC neurons can exhibit both in-phase and anti-phase synchrony
      and will often spontaneously alternate between these two states. This dictates
      that the local field oscillation amplitude is not simply linked to the extent of
      cell recruitment into a single synchronized neuronal assembly but also to the
      degree of destructive interference between dynamic, spatially overlapping,
      competing anti-phase groups of continuously bursting neurons. Thus, the waxing
      and waning of thalamic alpha/theta rhythms should not be assumed to reflect a
      wholesale increase and reduction, respectively, in underlying neuronal synchrony.
      We argue that these network dynamics might have important consequences for
      relating changes in the amplitude of EEG alpha and theta rhythms to the activity
      of thalamic networks.

PMID- 17000019
TI  - Engineering a novel, stable dimeric streptavidin with lower isoelectric point.
AB  - We have engineered a soluble, stable two-chain dimeric streptavidin (TCD) in
      Escherchia coli. Examination of the three-dimensional structure of streptavidin
      aided by empirical binding free-energy calculations helped us to select mutations
      at subunit interfaces that dissociate the native tetramer and stabilize the
      desired dimer. We chose positions W120, L124, V125 and H127 and mutated them to
      120D/124D/125D/127D (TCD-1); 120D/124N/125S/127D (TCD-2); and 120D/124D/125S/127D
      (TCD-3). The H127D mutation creates electrostatic repulsion that disrupts the
      dimer-dimer interface, but leaves it very hydrophobic. Therefore, W120, L124 and
      V125 were mutated to hydrophilic residues to increase dimer solubility. Among the
      three candidates, TCD-2 gave the best result: a stable, active dimer with K(d)
      for biotin of approximately 1x10(-7)M after purification by gel-filtration
      chromatography. The experimental results confirm the possibility of rational
      engineering of low-pI dimeric streptavidins. Reduced-size streptavidin mutants
      with a net negative charge may be more suitable than antibodies or wild-type
      streptavidin for the targeting step in radioimmunotherapy because they should
      clear faster from the bloodstream and the kidney.

PMID- 17000020
TI  - [Comparison between the terminal motor pudendal nerve terminal motor latency, the
      localization of the perineal neuralgia and the result of infiltrations. Analysis
      of 53 patients].
AB  - AIM: The aim is to study the value of the pudendal nerve terminal motor latency
      (PNTML) testing, in respect to the painful side in patients with pudenda
      neuralgia, and to determine whether a possible increased latency in the painful
      side is predictive of a good result with the infiltration. METHOD: This
      retrospective study included 53 outpatients (42 women, mean age 62) with
      suffering from pudendal neuralgia, who were seen between 2000 and 2004. The mean
      duration of the pain was 30+/-47 months. The PNTMPNL was measured by the Saint
      Mark hospital technique, by the same operator. The following criteria have been
      were defined: significant increased latency greater than above 6 ms, significant
      difference of 2 ms in latency between 2 sides from 2 ms, and side of the
      infiltration corresponding to the side of the neuralgia. The infiltrations were
      performed either by perineal (30 cases) or transgluteal (8 cases) way. The
      results on pain were have been considered as good when a substantial reduction of
      the pain was observed for 6 months or more. Statistical analysis involved was
      done by the exact Fischer's test to seek for a possible relation between
      variables. RESULTS: Of 53 patients (42 women, 11 men, mean age 62) suffered from
      a with perineal neuralgia. The duration of the neuralgia was 30+/-47 months. It
      was bilateral in 10 cases and unilateral in 43 cases. In 43 patients with When
      the pain was unilateral pain, PNTML we find that the MDLPN was increased in both
      sides in 39.5% of the population, in the painful side in 14% and in the side
      opposite side of the to pain in 11%. In 10 patients with the neuralgia was
      bilateral pain, in 10 patients. Among then, 4 had a bilateral increase of the
      latency, one patient had an increase only on the right side, and another one an
      increase only on the left side. We did not find any correlation between the
      increased of the PNTML TMPNL and, either neither the duration of the neuralgia
      nor the result of the infiltrations, whatever the method way of the infiltration.
      CONCLUSION: The PNTML can be increased whether it corresponds or not to an
      entrapment of the pudendal nerve. Thus, the management of perineal pain is based
      mainly, from us, on clinical findings.

PMID- 17000021
TI  - No independent role of the -1123 G>C and+2740 A>G variants in the association of
      PTPN22 with type 1 diabetes and juvenile idiopathic arthritis in two Caucasian
      populations.
AB  - INTRODUCTION: The PTPN22 is a negative regulator of the T cell response. Its
      +1858C>T (R620W) polymorphism has been shown to associate with a risk for
      multiple autoimmune diseases, including type 1 diabetes (T1D) and juvenile
      idiopathic arthritis (JIA). The minor (susceptibility) allele is absent in Asian
      populations, but a recent study suggested an independent involvement of another
      polymorphism located within the promoter -1123 nucleotides relative to the
      translational start site. AIMS: We aimed to analyse the association of three
      PTPN22 polymorphisms in two distinct Caucasian populations, the Czechs (with T1D
      and with JIA) and Azeri (with T1D). METHODS: The single nucleotide polymorphisms
      (SNP) at positions -1123 (rs2488457), +1858 (rs2476601, the R620W substitution),
      and +2740 (rs1217412) were genotyped using TaqMan assays in 372 subjects with
      childhood-onset T1D, 130 subjects with JIA, and 400 control subjects of Czech
      origin, and in 160 subjects with T1D and 271 healthy controls of Azeri origin.
      RESULTS: In the Czechs, all three SNPs were in a tight linkage disequlibrium,
      while in the Azeri, the linkage disequlibrium was limited to between the promoter
      and 3'-UTR polymorphism, D'(-1123, +2740)=0.99, r(2)=0.72. Haplotype
      reconstruction via the expectation-maximization algorithm showed in both
      populations that only the haplotype containing the minor (W) allele at codon 620
      was associated with T1D (OR=2.26, 95% CI 1.68-3.02 in Czechs, OR=14.8, 95% CI 2.0
      651 in Azeri) or JIA (OR=2.43, 95% CI 1.66-3.56 in Czechs). The haplotypes having
      the wild-type (R) allele at codon 620 and minor alleles at -1123 and/or +2740
      were neutral as to the risk of autoimmune conditions in both populations.
      CONCLUSIONS: In two different Caucasian populations, the Czechs and the Azeri, no
      independent contribution can be detected either of the -1123 promoter SNP or the
      +2740 3'-UTR SNP, and only the minor allele at PTPN22 codon 620 contributes to
      the risk of autoimmunity.

PMID- 17000022
TI  - Characteristics of undiagnosed diabetes in community-dwelling French elderly: the
      3C study.
AB  - We aimed to assess clinical and socio-demographic characteristics of undiagnosed
      diabetes, including glucose control, in French community-living elderly people.
      Diagnosed and undiagnosed diabetes, impaired fasting glucose (IFG) and
      characteristics of subjects were assessed by interview, clinical examination and
      fasting blood glucose measures at the baseline visit of the Three-City (3C) study
      including 9294 people over 65 in three urban areas in France. In the Bordeaux
      sample, HbA1c was measured in diabetic and IFG subjects and in a sub-sample of
      non-diabetic subjects. The proportion of diagnosed diabetes, undiagnosed diabetes
      and IFG was, respectively, 8.2%, 1.4% and 3.6%. Diabetic and IFG subjects were
      more likely to be men, to suffer from hypertension and to be overweight. They
      were less likely to have a high income and more likely to have a lower
      educational level. These factors were unrelated to knowledge of diabetic status.
      In the Bordeaux sub-sample, 19.6% of the diagnosed diabetic subjects and 16.1% of
      those undiagnosed had an HbA1c greater than 8%. Prevalence of ischemic heart
      disease was more common in diagnosed than in undiagnosed diabetic subjects
      (P=.021). A significant number of undiagnosed elderly had poor glucose control
      suggesting a potential benefit for diabetes screening in the elderly.

PMID- 17000023
TI  - Linking palaeoenvironmental data and models to understand the past and to predict
      the future.
AB  - Complex, process-based dynamic models are used to attempt to mimic the intrinsic
      variability of the natural environment, ecosystem functioning and, ultimately, to
      predict future change. Palaeoecological data provide the means for understanding
      past ecosystem change and are the main source of information for validating long
      term model behaviour. As global ecosystems become increasingly stressed by, for
      example, climate change, human activities and invasive species, there is an even
      greater need to learn from the past and to strengthen links between models and
      palaeoecological data. Using examples from terrestrial and aquatic ecosystems, we
      suggest that better interactions between modellers and palaeoecologists can help
      understand the complexity of past changes. With increased synergy between the two
      approaches, there will be a better understanding of past and present
      environmental change and, hence, an improvement in our ability to predict future
      changes.

PMID- 17000024
TI  - The G-protein regulatory (GPR) motif-containing Leu-Gly-Asn-enriched protein
      (LGN) and Gialpha3 influence cortical positioning of the mitotic spindle poles at
      metaphase in symmetrically dividing mammalian cells.
AB  - We addressed the role of the G-protein regulatory (GPR) motif-containing Leu-Gly
      Asn-enriched protein (LGN) and G-proteins (Gialpha3) in the positioning of the
      spindle pole during mammalian cell division. Immunocytochemistry indicated that
      both LGN and Gialpha3 co-localized at the spindle pole and at the midbody and the
      cell cortex during the different phases of mitosis. In marked contrast to the
      positioning of the spindle pole at metaphase midway between the cell cortex and
      the metaphase plate, the spindle pole was juxtaposed with the cell cortex at
      metaphase following increased expression of Gialpha3 and LGN. This repositioning
      of the spindle pole required the interaction of LGN with Gialpha. The influence
      of LGN and Gialpha3 on the cortical positioning of the spindle pole likely
      reflects either stronger pulling forces on the spindle pole exerted from the cell
      cortex or increased pushing forces exerted on the spindle pole from the mitotic
      spindle indicating that these events are regulated by GPR motif-containing
      proteins and G-proteins independent of asymmetry.

PMID- 17000025
TI  - Biological function of laminin-5 and pathogenic impact of its deficiency.
AB  - The basement membrane glycoprotein laminin-5 is a key component of the anchoring
      complex connecting keratinocytes to the underlying dermis. It is secreted by
      keratinocytes as a cross-shaped heterotrimer of alpha3, beta3 and gamma2 chains
      and serves as a ligand of various transmembrane receptors, thereby regulating
      keratinocyte adhesion, motility and proliferation. In intact skin, laminin-5
      provides essential links to both the hemidesmosomal alpha6beta4 integrin and the
      collagen type VII molecules which form the anchoring fibrils inserting into the
      dermis. If the basement membrane is injured, laminin-5 production increases
      rapidly. It then serves as a scaffold for cell migration, initiates the formation
      of hemidesmosomes and accelerates basement membrane restoration at the dermal
      epidermal junction. Mutations of the laminin-5 genes or auto-antibodies against
      one of the subunits of laminin-5 may lead to a significant lack of this molecule
      in the epidermal basement membrane zone. The major contributions of laminin-5 to
      the resistance of the epidermis against frictional stress but also for basement
      membrane regeneration and repair of damaged skin are reflected by the phenotype
      of Herlitz junctional epidermolysis bullosa, which is caused by an inherited
      absence of functional laminin-5. This lethal disease becomes manifest in
      widespread blistering of skin and mucous membranes, impaired wound healing and
      chronic erosions containing exuberant granulation tissue. Here, we discuss
      current understanding of the biological functions of laminin-5, the pathogenic
      impact of its deficiency and implications on molecular approaches towards a
      therapy of junctional epidermolysis bullosa.

PMID- 17000026
TI  - Induction characteristics and response of photosynthetic quantum conversion to
      changes in irradiance in mulberry plants.
AB  - A study was conducted, using rapid time course of chlorophyll (Chl) fluorescence
      parameters, and light-response curves of Chl fluorescence parameters, to
      determine the induction requirements and response of photosystem II (PSII)
      photochemistry and non-photochemical reactions after changes in irradiance in
      greenhouse mulberry plants. The induction of PSII photochemistry rapidly
      approached to steady state after leaves were treated from darkness to low
      irradiance (LI). When irradiance of leaves changed from darkness to high
      irradiance (HI), a biphasic induction was observed. A slight photoinhibition
      occurred in the leaves exposed to sunlight coming to the greenhouse, whereas a
      chronic photoinhibition occurred in the leaves fully exposed to sunlight outside
      the greenhouse. The chronic photoinhibition was demonstrated by sustained
      reduction of maximal quantum yield of PSII photochemistry (Fv/Fm). Moreover, the
      leaves of mulberry plants in greenhouse were sensitive to abrupt changes in
      irradiance and the sensitivity of leaves suffered in a short-term (1h) high light
      treatment was reduced, based on the changes in photosynthetic quantum conversion.
      These results demonstrated an inducible response of photosynthetic quantum
      conversion to changes in irradiance in mulberry.

PMID- 17000027
TI  - Expression of rice acyl-CoA oxidase isoenzymes in response to wounding.
AB  - To elucidate the role of acyl-CoA oxidase (ACX; EC 1.3.3.6) in plants, the
      expression patterns of rice ACXs in response to wounding were characterized.
      Three isogenes of ACX were identified in the rice genome. The deduced proteins of
      OsACX1, OsACX2 and OsACX3 consist of 669, 699 and 685 amino acid residues,
      respectively. The results from reverse transcriptase-PCR indicate that OsACX1 is
      expressed in leaves, stems, and roots, but was barely detectable in germinating
      seeds. OsACX2 was expressed predominantly in seeds. Only OsACX1 was upregulated
      by wounding, both locally and systemically. The expression of OsACX2 and OsACX3
      remained unchanged. It is suggested that OsACX2 is involved in providing
      germinating seeds with sugar and energy, while OsACX1 plays a role in the
      synthesis of jasmonic acid in response to wounding.

PMID- 17000028
TI  - "Just three more bites": an observational analysis of parents' socialization of
      children's eating at mealtime.
AB  - The objective of this study was to describe comprehensively the structure and
      process of the childhood mealtime environment. A socioeconomically diverse sample
      of 142 families of kindergarteners (52% females) was observed at dinnertime using
      a focused-narrative observational system. Eighty-five percent of parents tried to
      get children to eat more, 83% of children ate more than they might otherwise
      have, with 38% eating moderately to substantially more. Boys were prompted to eat
      as often as girls and children were prompted to eat as many times in single- as
      in two-parent households. Children were very rarely restricted in their mealtime
      intake. High-SES parents used reasoning, praise, and food rewards significantly
      more often than low-SES families. Mothers used different strategies than fathers:
      fathers used pressure tactics with boys and mothers praised girls for eating.
      Future research should examine the meanings children ascribe to their parents'
      communications about food intake and how perceived parental messages influence
      the development of long-term dietary patterns. Interpreted alongside the evidence
      for children's energy self-regulation and the risk of disruption of these innate
      processes, it may be that parents are inadvertently socializing their children to
      eat past their internal hunger/satiety cues. These data reinforce current
      recommendations that parents should provide nutritious foods and children, not
      parents, should decide what and how much of these foods they eat.

PMID- 17000029
TI  - Two families of antimicrobial peptides with multiple functions from skin of
      rufous-spotted torrent frog, Amolops loloensis.
AB  - There are around 27 species of Amolops amphibian distributed in South-east of
      Asia. Seven antimicrobial peptides (AMPs) belonging to two different families
      were purified from skin of rufous-spotted torrent frog, Amolops loloensis, and
      designated brevinins-ALa, b, c, and d, and temporins-ALa, b, and c. The brevinins
      AL family which is structurally related to brevinins-1 from skin secretions of
      the European frog, Rana brevipoda, is composed of 24 amino acids and has an intra
      disulfide bridge at the C-terminus. The temporins-AL family, composed of 13 or 16
      amino acid residues, is related with temporins from the skin secretions of R.
      temporaria. The findings of this study will facilitate the solutions to the
      taxonomic questions of the ranid genus Amolops and Staurois. In the work of this
      paper, both brevinins-ALb and temporin-Ma induced mast cell degranulation and
      histamine release, and had cytotoxic activity toward solid tumor cell line
      HepG(2). Brevinins-ALb also exerted strong hemolytic activity while temporin-Ma
      had no such activity.

PMID- 17000030
TI  - Effect of beta-lactotensin on acute stress and fear memory.
AB  - beta-Lactotensin (beta-LT) is a bioactive peptide derived from bovine milk beta
      lactoglobulin and is a natural ligand for neurotensin receptors. We examined the
      effect of beta-LT on restraint stress and fear memory in mice. Mice subjected to
      acute restraint stress exhibited a decreased number of head-dips and increased
      head-dip latency compared to non-stressed controls in the hole-board test,
      reflecting increased stress-induced behaviors. However, prior administration of
      beta-LT improved the behaviors caused by stress. The anti-stress effect of beta
      LT was blocked by levocabastine, a neurotensin receptor subtype 2 (NTR2)
      antagonist. In the fear-conditioning test, the duration of freezing responses by
      cued fear conditioning was significantly reduced in mice administered beta-LT
      compared with control mice. These results suggest that beta-LT has an anti-stress
      effect and promotes the extinction of fear memory, which may be mediated by NTR2.

PMID- 17000031
TI  - Synthesis and cytotoxic evaluation of a series of resveratrol derivatives
      modified in C2 position.
AB  - Eleven C2-substituted derivatives of resveratrol (trans-3,4',5
      trihydroxystilbene, RES) were prepared by partial synthesis from RES and
      evaluated for their cytotoxic activities against a human nasopharyngeal
      epidermoid tumor cell line KB. Among them, compounds 2 and 3 were more active
      than 5-fluorouracil (5-FU), an anticancer drug, and compound 5f exhibited similar
      activity to 5-FU. On the basis of the biological results, structure-activity
      relationships were discussed.

PMID- 17000032
TI  - Design, synthesis and activity against Toxoplasma gondii, Plasmodium spp., and
      Mycobacterium tuberculosis of new 6-fluoroquinolones.
AB  - This paper reports on the rational design of a series of new 6-fluoroquinolones
      by QSAR analysis against Toxoplasma (T.) gondii, their synthesis, their
      biological evaluation against T. gondii and Plasmodium (P.) spp., and their
      effect on Mycobacterium (M.) tuberculosis DNA gyrase and growth inhibition. Of
      the 12 computer-designed 8-ethyl(or methoxy)- and 5-ethyl-8-methoxy-6
      fluoroquinolones predicted to be active against T. gondii, we succeeded in the
      synthesis of four 6-fluoro-8-methoxy-quinolones. The four 6-fluoro-8-methoxy
      quinolones are active on T. gondii but only one is as active as predicted. One of
      these four compounds appears to be an antiparasitical drug of great potential
      with inhibitory activities comparable to or higher than that of trovafloxacin,
      gatifloxacin, and moxifloxacin. They also inhibit DNA supercoiling by M.
      tuberculosis gyrase with an efficiency comparable to that of the most active
      quinolones but are poor inhibitors of M. tuberculosis growth.

PMID- 17000033
TI  - Synthesis and antimicrobial activity of new bromine-rich pyrrole derivatives
      related to monodeoxypyoluteorin.
AB  - The synthesis and antimicrobial activity of new pyrrole derivatives structurally
      related to monodeoxypyoluteorin are described. The insertion of a keto or
      methylene spacer between the phenol group and the pyrroloyl moiety of brominated
      2-(2'-hydroxybenzoyl)pyrroles leads to a decrease of the antibacterial activity.

PMID- 17000034
TI  - Dietary abscisic acid ameliorates glucose tolerance and obesity-related
      inflammation in db/db mice fed high-fat diets.
AB  - BACKGROUND & AIMS: Despite their efficacy in improving insulin sensitivity,
      thiazolidinediones (TZDs) are associated with a number of side effects (i.e.
      weight gain, hepatotoxicity, congestive heart failure) that have limited their
      use by millions of diabetic patients. We have investigated whether abscisic acid
      (ABA), a naturally occurring phytochemical with structural similarities to TZDs,
      could be used as an alternative to TZDs to improve glucose homeostasis. METHODS:
      We first examined whether ABA, similar to TZDs, activates PPARgamma in vitro. We
      next determined the lowest effective dose of dietary ABA (100 mg/kg) and assessed
      its effect on glucose tolerance, obesity-related inflammation, and mRNA
      expression of PPARgamma and its responsive genes in white adipose tissue (WAT) of
      db/db mice fed high-fat diets. RESULTS: We found that ABA induced transactivation
      of PPARgamma in 3T3-L1 pre-adipocytes in vitro. Dietary ABA-supplementation for
      36 days decreased fasting blood glucose concentrations, ameliorated glucose
      tolerance, and increased mRNA expression of PPARgamma and its responsive genes
      (i.e., adiponectin, aP2, and CD36) in WAT. We also found that adipocyte
      hypertrophy, tumor necrosis factor-alpha (TNF-alpha) expression, and macrophage
      infiltration in WAT were significantly attenuated in ABA-fed mice. CONCLUSIONS:
      These findings suggest that ABA could be used as a nutritional intervention
      against type II diabetes and obesity-related inflammation.

PMID- 17000035
TI  - Recombinant M. smegmatis vaccine targeted delivering IL-12/GLS into macrophages
      can induce specific cellular immunity against M. tuberculosis in BALB/c mice.
AB  - In the present study, we constructed a viable therapeutic vaccine of recombinant
      M. smegmatis mediated IL-12/GLS (granulysin) gene transfer into murine
      macrophages to exert the immunotherapy effects on the Mycobacterium tuberculosis
      infection. We tested this recombinant therapeutic vaccine in an in vivo study to
      determine its capability of stimulating host specific immune responses against M.
      tuberculosis. BALB/c mice intranasally immunized with the therapeutic vaccine
      developed an efficient Th1 protective immune response against M. tuberculosis
      which was equal to that of the BCG strain. Inoculation intranasally with this
      viable vaccine induced high level of serum IFN-gamma, IL-12 and IgG2a. The viable
      vaccine was capable of inducing purified protein derivative (PPD) antigen
      specific splenocytes proliferation and IFN-gamma production from T cells in
      spleens of the immunized mice. In addition, intranasally inoculation with the
      viable vaccine can induce PPD antigen-specific sIgA production in the broncho
      alveolar lavage fluid (BALF) of the immunized mice. No change of IL-4 level was
      found in all groups. The therapeutic mechanism of this viable vaccine against M.
      tuberculosis infection observed here appeared to be a result of the specific Th1
      immune response activated by mycobacterium antigen from M. smegmatis and the
      expression of sIL-12/GLS in alveolar macrophages via the M. smegmatis-mediated
      gene transfer method. This research demonstrates that the therapeutic gene can be
      introduced into a host by viable mycobacteria works to induce the host specific
      immune response against M. tuberculosis infection in vivo. Since this therapeutic
      vaccine can strongly induce specific Th1 responses against M. tuberculosis in
      BALB/c mice and has no obviously harmfulness to the host simultaneously, the
      recombinant vaccine might be a potential candidate therapeutic vaccine against
      tuberculosis.

PMID- 17000036
TI  - Monitoring temperatures in the vaccine cold chain in Bolivia.
AB  - This study monitored vaccine cold chain temperatures during routine DTP-HB-Hib
      vaccine shipments from central stores to 11 communities in 3 provinces of
      Bolivia. In all 11 monitored shipments, vaccines were exposed to freezing
      temperatures at one or more points. In each of the shipments, temperatures below
      0 degrees C were recorded for 2-50% of the monitoring period. Freezing occurred
      at almost every level of the cold chain distribution system, especially during
      district and health center storage and during transport to the province and
      district levels. Seven of the 11 shipments were exposed to temperatures above 8
      degrees C, although none were exposed to excessive heat longer than 1.3% of the
      total monitoring period.

PMID- 17000037
TI  - Halogenated organic contaminants and mercury in northern fulmars (Fulmarus
      glacialis): levels, relationships to dietary descriptors and blood to liver
      comparison.
AB  - The northern fulmar (Fulmarus glacialis) is an interesting candidate for the
      study of patterns and levels of halogenated organic contaminants (HOCs) since
      they accumulate high levels of certain HOCs. In the present study we
      characterized a suite of established and novel HOCs in northern fulmars breeding
      on Bjornoya in the Norwegian Arctic. A comparison between blood and liver HOC
      levels was made, and the levels were related to the ratios of heavier to lighter
      stable isotopes of nitrogen (15)N/(14)N (delta(15)N) and carbon (13)C/(12)C
      (delta(13)C) in muscle. A significant difference in congener patterns between
      blood and liver was found. The delta(13)C was not related to HOCs, neither in
      liver nor in blood. Weak correlations were found between delta(15)N and liver HOC
      levels. The 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) in
      northern fulmars were well above thresholds for reproductive effects in seabirds.

PMID- 17000038
TI  - Partitioning and source diagnostics of polycyclic aromatic hydrocarbons in rivers
      in Tianjin, China.
AB  - Water, suspended particulate matter (SPM), and sediment samples were collected
      from ten rivers in Tianjin and analyzed for 16 polycyclic aromatic hydrocarbons
      (PAHs), dissolved organic carbon (DOC), particulate organic carbon (POC) in SPM
      and total organic carbon (TOC) in sediment. The behavior and fate of PAHs
      influenced by these parameters were examined. Generally, organic carbon was the
      primary factor controlling the behavior of the 16 PAH species. Partitioning of
      PAHs between SPM and water phase was studied, and K(OC) for some PAH species were
      found to be significantly higher than the predicted values. The source of PAHs
      contamination was diagnosed by using PAH isomer ratios. Coal combustion was
      identified to be a long-term and prevailing contamination source for sediment,
      while sewage/wastewater source could reasonably explain a short-term PAHs
      contamination of SPM.

PMID- 17000039
TI  - Trace metal distribution in sediments of the Pearl River Estuary and the
      surrounding coastal area, South China.
AB  - Surface sediments and sediment cores collected at the Pearl River Estuary (PRE)
      and its surrounding coastal area were analysed for total metal concentrations,
      chemical partitioning, and Pb isotopic compositions. The distribution of Cu, Cr,
      Pb, and Zn demonstrated a typical diffusion pattern from the land to the
      direction of the sea. Two hotspots of trace metal contamination were located at
      the mixed zone between freshwater and marine waters. The enrichment of metals in
      the sediments could be attributed to the deposition of the dissolved and
      particulate trace metals in the water column at the estuarine area. The similar
      Pb isotopic signatures of the sediments at the PRE and its surrounding coastal
      area offered strong evidence that the PRE was a major source of trace metals to
      the adjacent coastal area. Slightly lower (206)Pb/(207)Pb ratios in the coastal
      sediments may indicate other inputs of Pb in addition to the PRE sources,
      including the inputs from Hong Kong and other parts of the region.

PMID- 17000040
TI  - Sequestration of a fluorinated analog of 2,4-dichlorophenol and metabolic
      products by L. minor as evidenced by 19F NMR.
AB  - Fate of halogenated phenols in plants was investigated using nuclear magnetic
      resonance (NMR) to identify and quantify contaminants and their metabolites.
      Metabolites of 4-chloro-2-fluorophenol (4-Cl-2-FP), as well as the parent
      compound, were detected in acetonitrile extracts using 19F NMR after various
      exposure periods. Several fluorinated metabolites with chemical shifts
      approximately 3.5 ppm from the parent compound were present in plant extracts.
      Metabolites isolated in extracts were tentatively identified as fluorinated
      chlorophenol conjugates through examination of signal-splitting patterns and
      relative chemical shifts. Signal intensity was used to quantify contaminant and
      metabolite accumulation within plant tissues. The quantity of 4-Cl-2-F
      metabolites increased with time and mass balance closures of 90-110% were
      achieved. In addition, solid phase 19F NMR was used to identify 4-Cl-2-FP which
      was chemically bound to plant material. This work used 19F NMR for developing a
      time series description of contaminant accumulation and transformation in aquatic
      plant systems.

PMID- 17000041
TI  - TOL plasmid transfer during bacterial conjugation in vitro and rhizoremediation
      of oil compounds in vivo.
AB  - Molecular profiling methods for horizontal transfer of aromatics-degrading
      plasmids were developed and applied during rhizoremediation in vivo and
      conjugations in vitro. pWW0 was conjugated from Pseudomonas to Rhizobium. The
      xylE gene was detected both in Rhizobium galegae bv. officinalis and bv.
      orientalis, but it was neither stably maintained in orientalis nor functional in
      officinalis. TOL plasmids were a major group of catabolic plasmids among the
      bacterial strains isolated from the oil-contaminated rhizosphere of Galega
      orientalis. A new finding was that some Pseudomonas migulae and Pseudomonas
      oryzihabitans strains harbored a TOL plasmid with both pWW0- and pDK1-type xylE
      gene. P. oryzihabitans 29 had received the archetypal TOL plasmid pWW0 from
      Pseudomonas putida PaW85. As an application for environmental biotechnology, the
      biodegradation potential of oil-polluted soil and the success of bioremediation
      could be estimated by monitoring changes not only in the type and amount but also
      in transfer of degradation plasmids.

PMID- 17000043
TI  - Oxidative destabilization of dissolved organics and E. coli in domestic
      wastewater through immobilized cell reactor system.
AB  - Domestic wastewater contains a considerable amount of pathogenic organisms
      besides non-biodegradable organics. The conventional technologies followed for
      the treatment of domestic wastewater are less efficient in removing pathogenic
      organisms despite substantial removal of dissolved organics. The focal theme of
      the present investigation was to use a chemo-autotrophic activated carbon
      oxidation (CAACO) system, an immobilized cell reactor using chemoautotrophs
      (Bacillus sp.) for the treatment of domestic wastewater. The oxidation of
      organics and Escherichia coli in wastewater is controlled by the parameters space
      time, O(2)/COD, bed height and cod loading. The scheme comprised of anaerobic
      treatment, sand filtration and CAACO treatment removed BOD. COD, Total organic
      carbon (TOC), dissolved protein, total Kjeldhal nitrogen (TKN) and bacterial
      count (most probable number (MPN)) by 81%, 92%, 84%, 94%, 93% and 99.9997%,
      respectively. The low concentration of E. coli in the CAACO-treated wastewater
      was completely eliminated through UV irradiation in 3 min at 254 nm.

PMID- 17000042
TI  - Mis-specified and non-robust mortality risk models for nasopharyngeal cancer in
      the National Cancer Institute formaldehyde worker cohort study.
AB  - An IARC (International Agency for Research on Cancer) working group categorized
      formaldehyde as a human carcinogen (Group 1) in 2004. A major component of the
      epidemiologic evidence evaluated by IARC to reach this decision was the analysis
      published by Hauptmann et al. [Hauptmann, M., Lubin, J. H., Stewart, P. A.,
      Hayes, R. B., Blair, A. 2004. Mortality from solid cancers among workers in
      formaldehyde industries. Am. J. Epidemiol. 159, 1117-1130.] of the National
      Cancer Institute (NCI) historical cohort comprising industrial workers exposed to
      formaldehyde in 10 U.S. plants. The NCI authors emphasized the relationship found
      between highest formaldehyde peak exposure and death from nasopharyngeal cancer
      (NPC). We performed two additional types of re-analyses of the NCI cohort data
      with focus on peak exposure and NPC mortality. The analyses were aimed at (1)
      investigating whether the model specification chosen by Hauptmann et al. (2004)
      was appropriate (interaction assessment) and (2) exploring the degree of
      instability of the risk estimates for NPC in relation to highest peak exposure
      (sensitivity analysis). Hauptmann et al. (2004) failed to account for an
      important interaction structure between plant group and the exposure variable
      that prohibits a generalization of formaldehyde effects within the NCI cohort
      and, in particular, beyond the NCI cohort. In addition, our sensitivity analysis
      demonstrates considerable uncertainties in the risk estimates and points
      convincingly to instability problems particularly related to Plant 1. Even a
      simple sensitivity model taking only one additional death into account produced a
      variation of the risk estimates beyond the instability conveyed by standard
      confidence intervals. The results of our current reanalysis of the NCI study do
      not support NCI's suggestion of a causal association with formaldehyde exposure
      and nasopharyngeal cancer. The decision by the IARC working group to reclassify
      formaldehyde as a Group 1 substance was clearly premature considering: (1) the
      missing evidence of an NPC excess from the large British and NIOSH cohort
      studies; (2) the absence of an association with formaldehyde and NPC in the
      independent and expanded study of Plant 1; and (3) the mis-specified and non
      robust internal analysis of the NCI cohort study brought to light in our current
      re-analysis. Thus, the 2004 IARC decision to reclassify formaldehyde as a Group 1
      substance should be reconsidered.

PMID- 17000044
TI  - Kinetic and equilibrium isotherm studies for the adsorptive removal of Brilliant
      Green dye from aqueous solution by rice husk ash.
AB  - The present study deals with the adsorption of Brilliant Green (BG) on rice husk
      ash (RHA). RHA is a solid waste obtained from the particulate collection
      equipment attached to the flue gas lines of rice husk fired boilers. Batch
      studies were performed to evaluate the influences of various experimental
      parameters like initial pH (pH0), contact time, adsorbent dose and initial
      concentration (C0) on the removal of BG. Optimum conditions for BG removal were
      found to be pH0 approximately 3.0, adsorbent dose approximately 6 g L(-1) of
      solution and equilibrium time approximately 5 h for the C0 range of 50-300 mg L(
      1). Adsorption of BG followed pseudo-second-order kinetics. Intra-particle
      diffusion does not seem to control the BG removal process. Equilibrium isotherms
      for the adsorption of BG on RHA were analyzed by Freundlich, Langmuir, Redlich
      Peterson (R-P), Dubnin-Radushkevich (D-R), and Temkin isotherm models using a non
      linear regression technique. Langmuir and R-P isotherms were found to best
      represent the data for BG adsorption onto RHA. Adsorption of BG on RHA is
      favourably influenced by an increase in the temperature of the operation. Values
      of the change in entropy (DeltaS0) and heat of adsorption (DeltaH0) for BG
      adsorption on RHA were positive. The high negative value of change in Gibbs free
      energy (DeltaG0) indicates the feasible and spontaneous adsorption of BG on RHA.

PMID- 17000045
TI  - Advanced prostate cancer: at last a role for medical oncologists.

PMID- 17000046
TI  - Lack of association of two chromosome 10q24 SNPs with Alzheimer's disease.
AB  - Several groups have reported evidence of linkage on chromosome 10 to late-onset
      Alzheimer's disease (LOAD). In a recent scan of single nucleotide polymorphisms
      (SNPs) on chromosome 10, significant associations between the rs498055 and
      rs4417206 SNPs and risk of LOAD were observed. We examined the association of
      these two SNPs with LOAD risk in a large Caucasian American cohort comprising
      about 2000 cases and controls. Neither SNP revealed significant association with
      LOAD risk or age-at-onset.

PMID- 17000047
TI  - Serotonin 2A receptor gene is associated with personality traits, but not to
      disorder, in patients with borderline personality disorder.
AB  - Borderline personality disorder (BPD) is a chronic, disabling, and high-risk
      mental disorder characterized by a pervasive pattern of instability in regulation
      of emotion, interpersonal relationships, self-image, and impulse control
      beginning in early adulthood. BPD affects about 1%-2% of the general population
      and has a high mortality rate as a result of suicide and impulsive behaviour. The
      serotonin 2A receptor gene (HTR2A) is considered a candidate gene for BPD because
      multiple lines of evidence suggest that it plays an important role in suicide,
      impulsivity and emotional liability. To test for an association between HTR2A and
      BPD, we genotyped four polymorphisms, rs6313 (T102C), rs4941573, rs2296972 and
      rs6314 (His452Tyr), in 111 Caucasian patients with BPD and 287 Caucasian healthy
      controls. The program UNPHASED was used to compare allele and haplotype
      frequencies between cases and controls. We did not find a significant association
      between HTR2A and BPD based on allele, genotype or haplotype analyses. However,
      there were significant associations between HTR2A and personality traits in the
      BPD patients. The C allele of rs6313 and the A allele of rs4941573 associated
      with a higher Extraversion score. Our results suggest that the serotonin 2A
      receptor gene may not play a major role in the aetiology of borderline
      personality disorder, but may have a role in personality traits.

PMID- 17000048
TI  - Different roles of dopamine receptor subtypes in footshock stress-induced
      enhancement of morphine conditioned place preference.
AB  - The present study investigated the involvement of dopamine mechanism in the
      effect of intermittent footshock stress on the morphine-induced place preference.
      A single intermittent footshock session significantly enhanced the place
      preference induced by 3.0mg/kg morphine. This enhancing effect was inhibited by
      selective D(1) receptor antagonist SCH23390 and selective D(2) receptor
      antagonist sulpiride pretreatment 20min before footshock session, suggesting
      dopamine D(1) and D(2) receptors are required for the development of intermittent
      footshock stress-induced enhancement of morphine-associated place preference.
      However, different from D(1) and D(2) receptors this enhancing effect was blocked
      by stimulation of dopamine D(3) receptor with selective D(3) receptor agonist 7
      OH-DPAT pretreatment 20min before footshock session which suggest dopamine D(3)
      receptor play a negative mediation effect on the intermittent footshock stress
      induced this enhancement. These results indicate that dopamine D(1), D(2), and
      D(3) receptor subtypes play different roles in footshock stress-induced
      enhancement of morphine conditioned place preference.

PMID- 17000049
TI  - Insertional polymorphism of endogenous retrovirus HERV-K115 in schizophrenia.
AB  - Retroviruses are implicated in the pathogenesis of schizophrenia. Human
      endogenous retrovirus type K115 (HERV-K115) is a full-length, potentially
      transcriptional retrovirus and is also polymorphic. We investigated the frequency
      of HERV-K115 in Japanese schizophrenia patients and healthy controls. No
      difference was found in the frequency between patients and controls (8.4% versus
      9.4%, respectively). However, a marginal difference was observed in age at onset
      between the HERV-K positive and negative patients (p=0.057). The HERV-K115
      insertion appeared to be more frequent in patients with younger onset than those
      with later onset. These results preliminarily suggest that HERV-K115 may not be
      associated with schizophrenia in general, but that it could play a partial role
      in early precipitation of the disease.

PMID- 17000050
TI  - Recreational use of Psoralens to fortify skin tanning.

PMID- 17000051
TI  - Characterization strategies for the functional assessment of the cutaneous
      lesion.
AB  - Assessment of wound healing is a complex task, especially when the lesion is
      associated to significant (full thickness) loss of the skin. The clinical
      observation, essentially subjective and highly dependent on the observer's
      experience, creates difficulties in the comparison of results. Scoring scales
      were introduced in the clinical practice to create comparable semi-quantitative
      data and promote better management of resources, but its usefulness in a clinical
      perspective is still limited. New non-invasive biometric methodologies, although
      infrequently used, have opened new possibilities. While complementing the
      clinical observation and contributing to therapeutic decisions and prognosis,
      they may also help to look further into the pathophysiological mechanisms of
      scarring drugs rehabilitation. Following previous work in this arena, the authors
      review, the state-of-the-art of cutaneous wound healing clinical and biometric
      follow up, proposing a diagnosis correlation for the most relevant descriptors
      found in both strategies in order to fully characterise the different stages of
      the healing process.

PMID- 17000052
TI  - Electric field-induced changes in membrane proteins charge movement currents.
AB  - Our previous study showed that thermal effects induced by Joule heating did not
      play the pivotal role in damage of membrane proteins when cell membranes were
      shocked by a pulsed membrane potential up to 500 mV. Our analytical study of ion
      channel currents further indicated that a brief electric shock may cause protein
      conformational damage in the channel gating system, resulting in a reduction in
      the number of limiting gating charge particles. In this paper, we present the
      results of our study into electric shock-induced changes in the intramembrane
      charge movement currents. We found that a brief electric shock may significantly
      alter the characteristics of the charge movement currents of the membrane
      proteins, including reducing the magnitudes of two components Q(beta) and
      Q(gamma), broadening the hump shape of Q(gamma), and increasing its time delay.
      This study suggests that a brief intensive electric shock may cause proteins to
      structurally alter, reducing the amount of movable charge particles and therefore
      decreasing the protein functions. These results indicate that electro-coupled
      structural damage in membrane proteins is an important mechanism involved in
      electrical injury, especially in a field range not sufficient to cause thermal
      damage.

PMID- 17000053
TI  - The effect of N-methyl-D-aspartate receptor blockade on acetylcholine efflux in
      the dorsomedial striatum during response reversal learning.
AB  - Separate experiments found that activation of N-methyl-d-aspartate (NMDA)
      receptors or increased acetylcholine (ACh) efflux in the rat dorsomedial striatum
      is critical for learning when conditions require a shift in strategies.
      Increasing evidence indicates that NMDA receptor activity affects cholinergic
      efflux in the basal ganglia. The present studies determined whether NMDA receptor
      blockade in the dorsomedial striatum with dl-2-amino-5-phosphonopentanoic acid
      (AP-5) affects dorsomedial striatal ACh output in a resting condition, as well as
      during response reversal learning. Experiment 1 investigated the effects of AP-5
      (12.5, 25 or 50 muM) infused into the dorsomedial striatum on ACh output in a
      resting condition. AP-5 infusion at 25 and 50 muM led to a 20% and 40% decrease
      in dorsomedial striatal ACh output, respectively. AP-5 (12.5 muM) infusion did
      not change dorsomedial striatal ACh output from basal levels. Experiment 2
      determined whether dorsomedial striatal ACh efflux increases during response
      reversal learning and whether AP-5, at a dose that does not affect basal levels,
      modifies response reversal learning and ACh efflux. Following acquisition of a
      response discrimination, rats had microdialysis probes bilaterally inserted into
      the dorsomedial striatum prior to the reversal learning test. After baseline
      samples, rats received a response reversal learning test for 30 min. Control rats
      rapidly improved in the reversal learning session while simultaneously exhibiting
      an approximately 40% increase in ACh output compared with baseline levels. AP-5
      (12.5 muM) treatment during testing significantly impaired response reversal
      learning while concomitantly blocking an increase in ACh output. These findings
      suggest that NMDA receptor activation in the dorsomedial striatum may facilitate
      a shift in response patterns, in part, by increasing ACh efflux.

PMID- 17000054
TI  - The role of extracellular calcium in exo- and endocytosis of synaptic vesicles at
      the frog motor nerve terminals.
AB  - In the present study we combined FM 1-43 imaging and electrophysiological
      recording of miniature end-plate currents (MEPCs) to determine the role of
      extracellular calcium in synaptic vesicle exo- and endocytosis at the frog motor
      nerve terminals. We replaced extracellular Ca2+ ions with other bivalent cations
      (Sr2+, Ba2+, Cd2+, Mg2+) or used a calcium-free solution and monitored
      fluorescent staining of the nerve terminals in the presence of caffeine, which
      promotes the release of Ca2+ from intracellular stores. Caffeine has induced FM1
      43 internalization only in the presence of bivalent cations in the external
      solution. The exposure of the neuromuscular junction to caffeine in a calcium
      free solution caused a reversible failure of FM 1-43 loading and an increase in
      the nerve terminal width. This effect of a calcium-free solution was not due to a
      decrease in exocytosis, because caffeine-induced FM1-43 unloading from the
      previously loaded nerve terminals, as well as a degree of the MEPCs frequency
      increase, was unchanged. We conclude that the presence of Ca2+ or other bivalent
      cations in extracellular space is necessary for endocytosis but not for
      exocytosis of synaptic vesicles, while transmitter release is promoted by efflux
      of Ca2+ from intracellular stores. The effect of extracellular Ca2+ on
      endocytosis might be driven by the non-specific interactions with membrane
      lipids.

PMID- 17000055
TI  - Sustained activation of Src-family tyrosine kinases by ischemia: a potential
      mechanism mediating extracellular signal-regulated kinase cascades in hippocampal
      dentate gyrus.
AB  - In the present report, we investigated the association between the sustained
      activation of Src family tyrosine kinases (primarily Src kinase) with the
      biphasic phosphorylation of extracellular signal-regulated kinase (ERK) induced
      by ischemia in the rat hippocampal CA3/dentate gyrus subfield. Post-ischemia
      reperfusion resulted in the phosphorylation of ERK in a Ras-dependent manner;
      down-regulation of NMDA receptors or Src family protein kinases by ketamine or 4
      amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2) potently
      antagonized the activation of ERK, indicating that NMDA receptors and Src family
      tyrosine kinases are essential for the up-regulation of ERK activity following
      ischemic stimuli. Additionally, an ischemia-induced association between RKIP and
      Raf-1 resulted in the inhibition of the ERK signaling cascade through an
      inhibition of Src-mediated Raf-1 phosphorylation at Tyr340/341 residues. This
      ischemia-induced inhibition of ERK was not associated with other downstream
      pathways involving Raf-1 phosphorylation at Ser 259 elicited by protein kinase B
      (Akt). Dissociation of Raf-1 from RKIP by 24 h reperfusion or (4S)-3-[(E)-but-2
      enoyl]-4-benzyl-2-oxazolidinone (locostatin) influenced the second phase of ERK
      activation elicited by the Src-Raf cassette. We propose that, following ischemia,
      the Src family tyrosine kinases are critical for modulation of the
      Ras/Raf/MEK/ERK cascade, in which RKIP is involved in biphasic phosphorylation of
      ERK via a blockade of Src-Raf cascades.

PMID- 17000056
TI  - Sleep does not enhance the recovery of deprived eye responses in developing
      visual cortex.
AB  - Monocular deprivation (MD) during a critical period of visual development
      triggers a rapid remodeling of cortical responses in favor of the open eye. We
      have previously shown that this process is enhanced by sleep and is inhibited
      when the sleeping cortex is reversibly inactivated. A related but distinct form
      of cortical plasticity is evoked when the originally deprived eye (ODE) is
      reopened, and the non-deprived eye is closed during the critical period (reverse
      monocular deprivation (RMD)). Recent studies suggest that different mechanisms
      regulate the initial loss of deprived eye responses following MD and the recovery
      of deprived eye responses following RMD. In this study we investigated whether
      sleep also enhances RMD plasticity in critical period cats. Using polysomnography
      combined with microelectrode recordings and intrinsic signal optical imaging in
      visual cortex we show that sleep does not enhance the recovery of ODE responses
      following RMD. These findings add to the growing evidence that different forms of
      plasticity in vivo are regulated by distinct mechanisms and that sleep has
      divergent roles upon different types of experience-dependent cortical plasticity.

PMID- 17000057
TI  - Childhood acute lymphoblastic leukemia is triggered by the introduction of
      immunization against diphtheria.
AB  - BACKGROUND: Childhood acute lymphoblastic leukemia has prenatal origin.
      Leukemogenic translocations originating during fetal life are insufficient for
      overt leukemia. Transgenic TEL-AML1 mice have failed to develop leukemia.
      Additional postnatal events are required for full leukemogenesis. The significant
      peak-age (2-5 years) first appeared after 1940 in Great Britain. Since then,
      childhood leukemia has almost unchangeable incidence. In 1940 the introduction of
      immunization against diphtheria on a national scale was begun in Great Britain.
      HYPOTHESIS: Childhood acute lymphoblastic leukemia is triggered by vaccination
      against diphtheria. TESTING THE HYPOTHESIS: Epidemiological survey for leukemia
      cases among "exemptors" and unvaccinated cases among ALL children should be done.
      Simultaneously, the transgenic TEL-AML1 mice should be vaccinated with the
      diphtheritic toxoid. IMPLICATIONS OF THE HYPOTHESIS: If there is no leukemia
      among the "exemptors", no unvaccinated among ALL, and some mice develop leukemia
      upon vaccination childhood leukemia will be prevented by massive neonatal
      screening for leukemogenic genetics and/or with a new vaccination schedule.

PMID- 17000058
TI  - Creation of a local 'fever' using an infrared lamp to cure a tooth abscess.

PMID- 17000059
TI  - Father Carlo Gnocchi as the founder of global human rehabilitation in Italy:
      Historical evidence supporting a medical hypothesis.

PMID- 17000060
TI  - Management of neonatal abstinence syndrome in neonates born to opioid maintained
      women.
AB  - Neonates born to opioid-maintained mothers are at risk of developing neonatal
      abstinence syndrome (NAS), which often requires pharmacological treatment. This
      study examined the effect of opioid maintenance treatment on the incidence and
      timing of NAS, and compared two different NAS treatments (phenobarbital versus
      morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers
      were included in this study. The mothers received methadone (n=22), slow-release
      oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective
      of maintenance treatment, all neonates showed APGAR scores comparable to infants
      of non-opioid dependent mothers. No difference was found between the three
      maintenance groups regarding neonatal weight, length or head circumference. Sixty
      percent (n=32) of neonates required treatment for NAS [68% in the methadone
      maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in
      the buprenorphine-maintained group (n=3)]. The mean duration from birth to
      requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for
      the buprenorphine-maintained group and 58 h for the methadone-maintained group.
      In neonates requiring NAS treatment, those receiving morphine required a
      significantly shorter mean duration of treatment (9.9 days) versus those treated
      with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is
      preferable for neonates suffering NAS due to opioid withdrawal.

PMID- 17000061
TI  - Antimicrobial susceptibility patterns of thermotolerant Campylobacter strains
      isolated from food animals in Ethiopia.
AB  - Thermotolerant Campylobacter spp. are frequent causes of diarrhoea in humans
      worldwide mostly originating from poultry. It has been suggested that extensive
      veterinary use of antibiotics is largely responsible for resistance in human
      isolates. During a 4-month period from January to April 2004, 192 Campylobacter
      spp. were isolated from fecal samples of 485 healthy food animals. The in vitro
      susceptibility to 12 antibiotics was determined by the agar disk diffusion
      method. Among the 192 Campylobacter spp. isolated, 135 (70.3%) were identified to
      be C. jejuni, 51 (26.6%) were C. coli and 6 (3.1%) were C. lari. C. jejuni was
      the most prevalent species in chickens (80.8%) versus 16.2% C. coli and 3.0% C.
      lari. All isolates found in pigs were C. coli. All strains were sensitive to
      chloramphenicol and ciprofloxacin and all were resistant to cephalothin. More
      than 90% of the strains were sensitive to clindamycin, erythromycin, gentamicin,
      nalidixic acid, norfloxacin, streptomycin and tetracycline. Resistance was found
      against ampicillin in 20% and trimethoprim-sulphamethoxazole in 37.5%. Resistance
      was not statistically different among C. jejuni, C. coli and C. lari (p>0.05).
      Multidrug resistance to two or more drugs was detected in 14.5% of strains. In
      conclusion, the study showed that antimicrobial resistance is found only at
      relatively low frequencies for most antimicrobial agents tested except for
      ampicillin and trimethoprim-sulphamethoxazole. The low percentages of resistance
      to most antimicrobial agents tested in this study may be the result of low/no
      usage of these agents as a growth promoters or treatment in the Ethiopian animal
      farm setting. The detection of multidrug resistant isolates may pose a threat to
      humans and further limits therapeutic options.

PMID- 17000062
TI  - Follicle deviation and diurnal variation in circulating hormone concentrations in
      mares.
AB  - The temporal relationships between follicle deviation and systemic hormone
      concentrations were studied in mares. Blood samples were obtained at 01:00,
      07:00, 13:00, and 19:00 h from nine mares throughout an interovulatory interval.
      Diurnal variation in progesterone occurred on Days 4-12 and in LH on Days 4 and
      5; the lowest concentration for both hormones was at 13:00 h. Ultrasonically
      observed deviation in the ovulatory follicular wave began on Day 15.7+/-0.5
      (ovulation=Day 0). An increase (P<0.002) in LH began on Day 14 before the
      beginning of deviation, and an increase (P<0.05) in estradiol began at the
      beginning of deviation. Testosterone concentrations began to increase (P<0.05) 2
      days after the beginning of deviation and reached maximum 1 day before the next
      ovulation. The beginning of deviation was encompassed by a decline (P<0.003) in
      cortisol concentrations, and the concentrations remained low during the
      preovulatory period.

PMID- 17000063
TI  - A prospective analysis of alcohol consumption and onset of perimenopause.
AB  - OBJECTIVES: We prospectively assessed the association between alcohol consumption
      and onset of perimenopause in women of late reproductive age using data from the
      Harvard Study of Moods and Cycles. Specific types of alcoholic beverages - red
      wine, white wine, beer, and liquor - were evaluated. METHODS: Among 502 women
      aged 36-45 years residing in seven Boston communities, we assessed self-reported
      perimenopausal symptoms over a 5-year period. The onset of perimenopause was
      defined using changes in menstrual characteristics. We administered a
      semiquantitative food frequency questionnaire at enrollment to measure regular
      alcohol consumption during the past year. Hazard ratios (HRs) and 95% confidence
      intervals were derived from Cox regression models. RESULTS: No association was
      found between total alcohol consumption and time to perimenopause. Compared with
      women consuming <1 alcoholic drink per month, HRs for those drinking red wine in
      quantities of 1-3 glasses per month, 1 glass per week, or >or=2 glasses per week
      were all below 1.0, after accounting for other sources of alcohol. Among never
      smokers, the inverse association with red wine was stronger and a positive
      association was observed with liquor consumption although numbers were small. No
      associations were observed with white wine or beer. CONCLUSION: While there was
      no association between total alcohol consumption and onset of perimenopause,
      there was some suggestion of an inverse association between red wine and risk of
      perimenopause, particularly among never smokers.

PMID- 17000064
TI  - Blood or plasma to skin distribution of drugs: a linear free energy analysis.
AB  - Data on distribution coefficients from blood or plasma to rat skin and rabbit
      skin have been compiled. From previous work on blood/plasma to brain or to muscle
      it is apparent that distributions from blood and plasma can be combined, and we
      show that it is possible to combine data on distribution to rat skin and rabbit
      skin. The combined set of blood/plasma distribution to rat and rabbit skin for 59
      compounds, as logPskin, can be correlated through a linear free energy equation
      with a correlation coefficient of 0.856 and a standard deviation of 0.26 log
      units. The predictive capability of the equation has been assessed through
      training and test sets, and it is shown that the S.D. value of 0.26 log units is
      a good estimate of the predictive ability. The equation for logPskin has been
      compared to equations for a large number of possible model processes, using two
      mathematical methods. It is shown that there is no process amongst those we have
      examined that has any advantage over the present in silico linear free energy
      equation for the estimation of further values of logPskin.

PMID- 17000065
TI  - Formulation and characterization of amphotericin B-chitosan-dextran sulfate
      nanoparticles.
AB  - A new nanoparticulate delivery system for amphotericin B (AmB) has been developed
      by means of the polyelectrolyte complexation technique. Two opposite charged
      polymers were used to form nanoparticles through electrostatic interaction,
      chitosan (CH) as a positively charged polymer and dextran sulfate (DS) as a
      polymer with a negative charge, together with zinc sulfate as a crosslinking and
      hardening agent. The AmB nanoparticles obtained possessed a mean particle size of
      600-800 nm with a polydispersity index of 0.2, indicating a narrow size
      distribution. The measured zeta potential of the nanoparticle surface was
      approximately -32 mV indicating a strong negative charge at the particle's
      surface. Scanning electron microscopy revealed spherical particles with a smooth
      surface. Drug association efficacy of up to 65% was achieved. Dissolution studies
      demonstrated a fast release behavior suggesting that AmB exhibits only moderate
      interaction with the weakly crosslinked polymers of the nanoparticles. Although,
      electronic absorbance spectra showed that the aggregation state of AmB was
      modified within the nanoparticles, a reduction of nephrotoxicity was observed in
      an in vivo renal toxicity study.

PMID- 17000066
TI  - Morphology control of polylactide microspheres enclosing irinotecan hydrochloride
      with polylactide based polymer surfactant for reduction of initial burst.
AB  - We introduced newly biodegradable polymer surfactant to poly(D,L-lactide)
      microspheres for exhibiting precisely controlled release rate of antitumor agent.
      We newly designed biodegradable polymer surfactant, poly(ethyleneoxide
      monooleate)-block-poly(D,L-lactide); (MOPEO-PLA), which has a biocompatible, oil
      soluble and compatible with polylactide matrices. Polylactide (PLA) microspheres
      with MOPEO-PLA enclosing Irinotecan hydrochloride (CPT-11) was successfully
      fabricated by solvent evaporation method via O/O emulsion. The surface morphology
      was strongly affected to MOPEO-PLA content in PLA microspheres; the wrinkles on
      microsphere surface were decreased with increasing MOPEO-PLA content. It was
      found from DSC scans that Tg of PLA drastically decreased with introducing MOPEO
      PLA, indicating that MOPEO-PLA miscible with PLA. MOPEO-PLA, played as a
      plasticizer, made the surface smoothed. The rate of release in a short duration
      was minimum value at adding 20 wt.% of MOPEO-PLA. This result was due to the
      smaller surface area of PLA microspheres with smoothed surface.

PMID- 17000067
TI  - Effect of coupling of albumin onto surface of PEG liposome on its in vivo
      disposition.
AB  - To evaluate the effect of coupling of albumin onto the surface of poly(ethylene
      glycol)-modified liposome (PEG liposome) on the in vivo disposition of liposome,
      pharmacokinetics and tissue distribution were examined after intravenous
      administration of rat serum albumin-modified PEG (RSA/PEG) liposome into rats.
      RSA/PEG liposome showed longer blood-circulating property than PEG liposome and
      the hepatic clearance for RSA/PEG liposome was significantly smaller than that
      for PEG liposome. Single-pass liver perfusion experiments also showed that the
      hepatic disposition of RSA/PEG liposome was much less than that of PEG liposome
      and that pre-treatment of liver with trypsin did not significantly reduce the
      hepatic disposition of RSA/PEG liposome, suggesting that RSA/PEG liposome could
      avoid the hepatic uptake via the receptor-mediated endocytosis. To unravel the
      mechanism behind the less affinity of RSA/PEG liposome to the liver, serum
      proteins associated on their surface were quantitatively and qualitatively
      assessed. The results showed that the coupling of albumin onto PEG liposome
      significantly reduced the total amount of serum proteins associated onto the
      surface, and SDS-PAGE revealed that the decrease in the association with
      liposomes for several serum proteins, which might have opsonic activity. From
      these findings, introduction of serum albumin onto PEG liposome could be useful
      to develop a new nanoparticulate formulation with a better pharmacokinetic
      property.

PMID- 17000068
TI  - Temozolomide/PLGA microparticles and antitumor activity against glioma C6 cancer
      cells in vitro.
AB  - The purpose of the present study was to develop implantable poly(D,L-lactide-co
      glycolide) (PLGA) microparticles for continuous delivery of intact 3,4-dihydro-3
      methyl-4-oxoimidazo[5,1-d]-as-tetrazine-8-carboxamide (temozolomide, TM) for
      about a 1-month period and to evaluate its cytotoxicity against Glioma C6 cancer
      cells. The emulsifying-solvent evaporation process has been used to form TM
      loaded PLGA microparticles. The influences of several preparation parameters,
      such as initial drug loading, polymer concentration, and stirring rate were
      investigated. Scanning electron microscopy (SEM) showed that such microparticles
      had a smooth surface and a spherical geometry, i.e. microspheres. The
      differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD)
      results indicated that TM trapped in the microparticles existed in an amorphous
      or disordered-crystalline status in the polymer matrix. The release profiles of
      TM from microparticles resulted in biphasic patterns. After an initial burst, a
      continuous drug release was observed for up to 1 month. Finally, a cytotoxicity
      test was performed using Glioma C6 cancer cells to investigate the cytotoxicity
      of TM delivered from PLGA microparticles. It has been found that the cytotoxicity
      of TM to Glioma C6 cancer cells is enhanced when TM is delivered from PLGA
      polymeric carrier and, PLGA only did not affect the growth of the cells.
      Meanwhile, the cytotoxic activity of TM powder disappeared within 12h.

PMID- 17000069
TI  - Evaluation of the flora of northern Mexico for in vitro antimicrobial and
      antituberculosis activity.
AB  - The aim of the present study was to evaluate the potential antimicrobial activity
      of 14 plants used in northeast Mexico for the treatment of respiratory diseases,
      against drug-sensitive and drug-resistant strains of Streptococcus pneumoniae,
      Staphylococcus aureus, Haemophilus influenzae type b and Mycobacterium
      tuberculosis. Forty-eight organic and aqueous extracts were tested against these
      bacterial strains using a broth microdilution test. No aqueous extracts showed
      antimicrobial activity, whereas most of the organic extracts presented
      antimicrobial activity against at least one of the drug-resistant microorganisms
      tested. Methanol-based extracts from the roots and leaves of Leucophyllum
      frutescens and ethyl ether extract from the roots of Chrysanctinia mexicana
      showed the greatest antimicrobial activity against the drug-resistant strain of
      Mycobacterium tuberculosis; the minimal inhibitory concentration (MIC) were 62.5,
      125 and 62.5 microg/mL, respectively; methanol-based extract from the leaves of
      Cordia boissieri showed the best antimicrobial activity against the drug
      resistant strain of Staphylococcus aureus (MIC 250 microg/mL); the hexane-based
      extract from the fruits of Schinus molle showed considerable antimicrobial
      activity against the drug-resistant strain of Streptococcus pneumoniae (MIC 62.5
      microg/mL). This study supports that selecting plants by ethnobotanical criteria
      enhances the possibility of finding species with activity against resistant
      microorganisms.

PMID- 17000070
TI  - Effects and mechanisms of total glucosides of paeony on adjuvant arthritis in
      rats.
AB  - Total glucosides of paeony (TGP) is the major active constituent of Paeonia
      lactiflora Pall. The present study was carried out to investigate the effects of
      TGP on adjuvant arthritis (AA) of rat and its possible mechanisms. AA was induced
      by metatarsal footpad injection with complete Freund's adjuvant in male Sprague
      Dawley rats. The secondary inflammatory reaction was evaluated by hind paw
      swelling, polyarthritis index. Activity of interleukin-1 (IL-1) was detected by
      Con A-induced thymocytes proliferation of C57BL/6J mice assay. The tumor necrosis
      factor alpha (TNFalpha), prostaglandin E(2) (PGE(2)) and cyclic adenosine
      monophosphate (cAMP) levels in synoviocytes were assessed by radioimmunoassay
      (RIA). PGE(2) receptors, EP2 and EP4, were analyzed by Western blot analysis. The
      level of IL-6 was measured by ELISA. Intragastric administration of TGP (50,100
      mg/kg) significantly decreased secondary inflammatory reaction in AA rats.
      Suppressing the activity of IL-1 and TNFalpha, decreased PGE(2) and increased
      cAMP levels in synoviocytes of AA rats were observed after administration of TGP.
      In the immunoblot analysis, TGP could up-regulate the expression of EP2 and EP4.
      These results showed TGP significantly inhibited the progression of AA, and the
      inhibitory effects might be associated with its ability to mediate the level of
      cAMP and inhibit the production of IL-1, TNFalpha, IL-6 and PGE(2) from activated
      synoviocytes.

PMID- 17000071
TI  - Increasing conclusiveness of metabonomic studies by chem-informatic preprocessing
      of capillary electrophoretic data on urinary nucleoside profiles.
AB  - Nowadays, bioinformatics offers advanced tools and procedures of data mining
      aimed at finding consistent patterns or systematic relationships between
      variables. Numerous metabolites concentrations can readily be determined in a
      given biological system by high-throughput analytical methods. However, such row
      analytical data comprise noninformative components due to many disturbances
      normally occurring in analysis of biological samples. To eliminate those unwanted
      original analytical data components advanced chemometric data preprocessing
      methods might be of help. Here, such methods are applied to electrophoretic
      nucleoside profiles in urine samples of cancer patients and healthy volunteers.
      The electrophoretic nucleoside profiles were obtained under following conditions:
      100 mM borate, 72.5 mM phosphate, 160 mM SDS, pH 6.7; 25 kV voltage, 30 degrees C
      temperature; untreated fused silica capillary 70 cm effective length, 50 microm
      I.D. Different most advanced preprocessing tools were applied for baseline
      correction, denoising and alignment of electrophoretic data. That approach was
      compared to standard procedure of electrophoretic peak integration. The best
      results of preprocessing were obtained after application of the so-called
      correlation optimized warping (COW) to align the data. The principal component
      analysis (PCA) of preprocessed data provides a clearly better consistency of the
      nucleoside electrophoretic profiles with health status of subjects than PCA of
      peak areas of original data (without preprocessing).

PMID- 17000072
TI  - Differential regulation of the neuronal isoform of nitric oxide synthase in the
      superior colliculus and dorsal lateral geniculate nucleus of the adult rat brain
      following eye enucleation.
AB  - Nitric oxide has been shown to play various physiological and pathological roles
      in the visual system. We studied here the expression of the neuronal isoform of
      nitric oxide synthase in the rat superior colliculus and in the dorsal lateral
      geniculate nucleus after unilateral enucleation, by means of
      immunohistochemistry, immunoblotting, and real-time PCR. Immunohistochemistry
      revealed an increase of nitric oxide synthase-positive neurons in specific layers
      of the superior colliculus and in the dorsal lateral geniculate nucleus between 1
      and 30 days post-lesion. Immunoblotting analyses confirmed that the neuronal
      isoform of nitric oxide synthase is upregulated in the superior colliculus and in
      the dorsal lateral geniculate nucleus after retinal removal. Diaminofluorescein
      histochemistry suggested that nitric oxide production was increased in both
      deafferented retinorecipient areas. Our real-time PCR results indicated that
      nitric oxide synthase transcript levels in the superior colliculus were not
      significantly altered after monocular enucleation, although an upregulation of
      the enzyme transcription was detected into the deafferented dorsal lateral
      geniculate nucleus. These findings indicated that neuronal nitric oxide synthase
      may undergo different forms of regulation in the adult deafferented visual
      system.

PMID- 17000073
TI  - Cultural influences on the physician-patient encounter: The case of shared
      treatment decision-making.
AB  - OBJECTIVE: In this paper we discuss the influence of culture on the process of
      treatment decision-making, and in particular, shared treatment decision-making in
      the physician-patient encounter. We explore two key issues: (1) the meaning of
      culture and the ways that it can affect treatment decision-making; (2) cultural
      issues and assumptions underlying the development and use of treatment decision
      aids. METHODS: This is a conceptual paper. Based on our knowledge and reading of
      the key literature in the treatment decision-making field, we looked for written
      examples where cultural influences were taken into account when discussing the
      physician-patient encounter and when designing instruments (decision aids) to
      help patients participate in making decisions. RESULTS: Our assessment of the
      situation is that to date, and with some recent exceptions, research in the above
      areas has not been culturally sensitive. CONCLUSION: We suggest that more
      research attention should be focused on exploring potential cultural variations
      in the meaning of and preferences for shared decision-making as well as on the
      applicability across cultural groups of decision aids developed to facilitate
      patient participation in treatment decision-making with physicians. PRACTICE
      IMPLICATIONS: Both patients and physicians need to be aware of the cultural
      assumptions underlying the development and use of decision aids and assess their
      cultural sensitivity to the needs and preferences of patients in diverse cultural
      groups.

PMID- 17000074
TI  - To know or not to know: a review of behaviour and suicidal ideation in
      preclinical Huntington's disease.
AB  - OBJECTIVE: At present, the problems associated with suicidal ideation and suicide
      in Huntington's disease (HD), worldwide, are much the same as 2 decades ago. This
      study seeks to investigate the psychological complications of predictive testing
      in HD at risk populations. METHODS: The key problems of predictive testing, fear
      of acquiring carrier status, psychological consequences, autonomy, and rights to
      know are discussed. RESULTS: This review (1) describes psychological affect and
      problems of persons facing the decision to test for HD, (2) discusses suicidal
      ideation, behaviour, and catastrophic events associated with predictive testing,
      (3) assesses ethical questions raised in the genetic counselling, (4) questions
      whether counsellors should promote or advocate predictive testing, and finally
      (5) discusses what professionalism actually is in genetic counselling.
      CONCLUSION: The need for professional counselling, using a well designed
      protocol, and the importance of focusing on the suicide risk of participants in
      predictive testing programs are emphasized. PRACTICE IMPLICATIONS: The counsellor
      has an obligation to provide adequate information. The professionals should not
      promote nor advocate presymptomatic DNA-testing. Depression, hopelessness,
      anxiety, emotional distress, suicidal tendencies, and social dysfunction grading
      should be considered in predictive testing of HD.

PMID- 17000075
TI  - The effects of the type of anesthesia on outcomes of lower extremity
      infrainguinal bypass.
AB  - OBJECTIVE: Three main types of anesthesia are used for infrainguinal bypass:
      general endotracheal anesthesia (GETA), spinal anesthesia (SA), and epidural
      anesthesia (EA). We analyzed a large clinical database to determine whether the
      type of anesthesia had any effect on clinical outcomes in lower extremity bypass.
      METHODS: This study is an analysis of a prospectively collected database by the
      National Surgical Quality Improvement Program (NSQIP) of the Veterans Affairs
      Medical Centers. All patients from 1995 to 2003 in the NSQIP database who
      underwent infrainguinal arterial bypass were identified via Current Procedural
      Terminology codes. The 30-day morbidity and mortality outcomes for various types
      of anesthesia were compared by using univariate analysis and multivariate
      logistic regression to control for confounders. RESULTS: The NSQIP database
      identified 14,788 patients (GETA, 9757 patients; SA, 2848 patients; EA, 2183
      patients) who underwent a lower extremity infrainguinal arterial bypass during
      the study period. Almost all patients (99%) were men, and the mean age was 65.8
      years. The type of anesthesia significantly affected graft failure at 30 days.
      Compared with SA, the odds of graft failure were higher for GETA (odds ratio,
      1.43; 95% confidence interval [CI], 1.16-1.77; P = .001). There was no
      statistically significant difference in 30-day graft failure between EA and SA.
      Regarding cardiac events, defined as postoperative myocardial infarction or
      cardiac arrest, patients with normal functional status (activities of daily
      living independence) and no history of congestive heart failure or stroke did
      worse with GETA than with SA (odds ratio, 1.8; 95% CI, 1.32-2.48; P < .0001).
      There was no statistically significant difference between EA and SA in the
      incidence of cardiac events. GETA, when compared with SA and EA, was associated
      with more cases of postoperative pneumonia (odds ratio: 2.2 [95% CI, 1.1-4.4; P =
      .034]. There was no significant difference between EA and SA with regard to
      postoperative pneumonia. Compared with SA, GETA was associated with an increased
      odds of returning to the operating room (odds ratio, 1.40; 95% CI, 1.20-1.64; P <
      .001), as was EA (odds ratio, 1.17; 95% CI, 1.05-1.31; P = .005). GETA was
      associated with a longer surgical length of stay on univariate analysis, but not
      after controlling for confounders. There was no significant difference in 30-day
      mortality among the three groups with univariate or multivariate analyses.
      CONCLUSIONS: Although GETA is the most common type of anesthesia used in
      infrainguinal bypasses, our results suggest that it is not the best strategy,
      because it is associated with significantly worse morbidity than regional
      techniques.

PMID- 17000076
TI  - Outcome of common iliac arteries after straight aortic tube-graft placement
      during elective repair of infrarenal abdominal aortic aneurysms.
AB  - PURPOSE: To determine the relative rates of common iliac artery (CIA) expansion
      after elective straight aortic tube-graft replacement of infrarenal abdominal
      aortic aneurysms (AAA). METHODS: Five participating centers in this 2004 study
      entered patients they had managed by an aortoaortic tube graft for elective AAA
      repair. The procedures took place between January 1995 and December 2003.
      Postoperative computed tomography (CT) scans were obtained for all patients in
      2004 to assess changes in CIA diameter. Measurements on preoperative and
      postoperative CT scans were all made at the same level using the same technique.
      RESULTS: Entered in the study were 147 patients (138 men, 9 women) with a mean
      age of 68 years. Mean follow-up from aortic surgery to verification of CIA
      diameter on the postoperative CT scan was 4.8 years. Mean preoperative CIA
      diameter was 13.6 mm vs 15.2 mm postoperatively. No patient developed occlusive
      iliac artery disease during follow-up. Three patients (2%) required repeat
      surgery during follow-up for a CIA aneurysm. The 147 patients were divided into
      three groups based on preoperative CIA diameter shown in CT scan: group A (n =
      59, 40.1%), both CIA were of normal diameter; group B (n = 53, 36.1%), ectasia
      (diameter between 12 and 18 mm) of at least one CIA; group C (n = 35, 23.8%), an
      aneurysm (diameter >18 mm) of at least one CIA. CIA diameter increased by a mean
      of 1 mm (9.4%) over 5.5 years in group A vs 1.7 mm (12.1%) over 4.3 years in
      group B and 2.3 mm (12.7%) over 4.2 years in group C. The three patients who
      required repeat surgery for a CIA aneurysm during follow-up were all in group C.
      Four variables were associated with aneurysmal change in CIA: initial CIA
      diameter, celiac aorta diameter on the preoperative CT scan, a coexisting
      aneurysm site, and the follow-up duration. CONCLUSIONS: Tube-graft placement
      during AAA surgery is justified even for moderate CIA dilatation (<18 mm). CIA
      aneurysms with a preoperative diameter > or =25 mm enlarge more rapidly and
      warrant insertion of a bifurcated graft during the same surgical session as AAA
      repair. The evolutive potential of CIA between 18 mm and 25 mm in diameter
      justifies a bifurcated graft when the celiac aorta diameter is >25 mm or the
      patient's life expectancy is > or =8 years.

PMID- 17000077
TI  - State-of-the-art treatment of chronic leg ulcers: A randomized controlled trial
      comparing vacuum-assisted closure (V.A.C.) with modern wound dressings.
AB  - BACKGROUND: Current treatment modalities for chronic leg ulcers are time
      consuming, expensive, and only moderately successful. Recent data suggest that
      creating a subatmospheric pressure by vacuum-assisted closure (V.A.C., KCI
      Concepts, San Antonio, Texas) therapy supports the wound healing process.
      METHODS: The efficacy of vacuum-assisted closure in the treatment of chronic leg
      ulcers was prospectively studied in a randomized controlled trial in which 60
      hospitalized patients with chronic leg ulcers were randomly assigned to either
      treatment by V.A.C. or therapy with conventional wound care techniques. The
      primary outcome measure was the time to complete healing (days). Statistical
      analysis was performed on the intention-to-treat basis. RESULTS: The median time
      to complete healing was 29 days (95% confidence interval [CI], 25.5 to 32.5) in
      the V.A.C. group compared with 45 days (95% CI, 36.2 to 53.8) in the control
      group (P = .0001). Further, wound bed preparation during V.A.C. therapy was also
      significantly shorter at 7 days (95% CI 5.7 to 8.3) than during conventional
      wound care at 17 days (95% CI, 10 to 24, P = .005). The costs of conventional
      wound care were higher than those of V.A.C. Both groups showed a significant
      increase in quality of life at the end of therapy and a significant decrease in
      pain scores at the end of follow-up. CONCLUSIONS: V.A.C. therapy should be
      considered as the treatment of choice for chronic leg ulcers owing to its
      significant advantages in the time to complete healing and wound bed preparation
      time compared with conventional wound care. Particularly during the preparation
      stage, V.A.C. therapy appears to be superior to conventional wound care
      techniques.

PMID- 17000078
TI  - Deception strategies in children: examination of forced choice recognition and
      verbal learning and memory techniques.
AB  - Thirty-five children ages 6-12 years were asked to complete two alternate forms
      of the Hopkins Verbal Learning Test-Revised (HVLT-R), once with the instruction
      to feign cognitive impairment and once instructed to do their best. They were
      also asked to complete the Test of Memory Malingering (TOMM). Regardless of
      condition, children performed comparably to adult norms on the TOMM, obtaining a
      score of 45 or above on Trial 2. Regarding the HVLT-R, differences emerged only
      when children were initially told to "do their best," followed by a subsequent
      trial in which they were told feign impairment. Within this group of
      participants, children demonstrated significantly lower levels of learning across
      trials and fewer words recalled in comparison to when they were instructed to do
      their best. In contrast, no reliable differences on the HVLT-R were observed
      among children who were initially told to feign impairment and subsequently told
      to do their best. These results suggest that the elicitation of "feigned"
      impairment within this age group on the HVLT-R requires the initial provision of
      an opportunity for optimal performance.

PMID- 17000079
TI  - In vitro effects of dexamethasone on mouse ovarian function and pre-implantation
      embryo development.
AB  - The effect of dexamethasone (5-80 microg/ml) on ovarian function and embryo
      development was studied in mice. The follicle bio-assay revealed no effects of
      DEX up to 40 microg/ml on folliculogenesis and oogenesis, whereas 80 microg/ml
      hampered follicle differentiation and oocyte maturation. Androgen, estrogen and
      progestin secretion patterns were strongly impaired at all doses levels. However,
      the ovulation-induced progesterone increase indicating that the steroid pathway
      was activated in presence of DEX. Applying the oil-free mouse embryo assay no
      alteration of DEX on the first cleavage stages were observed whereas blastocyst
      rate decreased from 20 microg/ml DEX onwards, and hatching capacity was already
      impaired in presence of 10 microg/ml DEX. In conclusion, steroidogenesis was
      affected from 5 microg/ml onwards and the minimum effective inhibitory dose was
      set at 10 microg/ml for early embryo development. Based on these in vitro
      findings, physiological or therapeutic levels of glucocorticosteroids are
      unlikely to affect female fertility.

PMID- 17000080
TI  - Clinical review of three types of platysma myocutaneous flap.
AB  - This study evaluated the survival rates of three types of platysma myocutaneous
      flap: transverse flap, vertical flap that preserved the facial artery and vein
      and vertical flap that sacrificed the facial artery and vein. Modified radical or
      supraomohyoid neck dissection was also performed in all patients. Out of 54
      patients, transverse and vertical flaps were used for 12 and 42 cases,
      respectively. In 42 cases of vertical flaps, 26 cases preserved the facial artery
      and vein, 16 cases sacrificed them. Ten cases of the transverse flaps survived
      and two cases had partial necrosis. In the 26 cases of vertical flaps that
      preserved the facial artery and vein, 23 cases survived and three cases had
      partial necrosis. With the 16 cases of vertical flaps that sacrificed the facial
      artery and vein, 10 cases survived, four cases had partial necrosis and two cases
      had total necrosis. The flap survival rates were 83.3, 88.5 and 62.5%,
      respectively, in the transverse, vertical flap preserving the facial vessels and
      vertical flap that sacrificed them. The survival rates of transverse and vertical
      platysma myocutaneous flaps preserving the facial artery and vein were higher
      than vertical flap that sacrificed the facial artery and vein.

PMID- 17000081
TI  - Metabolic correlates of epileptic spikes in cerebral cavernous angiomas.
AB  - BACKGROUND: Cerebral cavernous angiomas (CCA) are frequently associated with
      focal intractable epilepsy. Epileptogenicity is usually attributed to hemosiderin
      deposits. Combined recording of electroencephalogram (EEG) and functional
      magnetic resonance imaging (fMRI) is a new method to investigate epileptic
      discharges. METHODS: We used EEG-fMRI to identify BOLD responses to interictal
      spikes in patients with CCA. Responses were analyzed in the lesional and
      perilesional area, and at distance. RESULTS: Eight patients were scanned, all
      with temporal lobe epilepsy and spikes. One patient had bilateral spikes,
      analyzed separately, and three studies with less than two spikes were excluded.
      All six studies analyzed showed BOLD responses. No response was found in the
      lesion itself or immediate periphery, and the raw fMRI signal showed signal loss
      in lesional and perilesional areas in all patients. Responses were close to the
      perilesional area in 2/6 studies. All patients showed responses at a distance
      from the lesions. CONCLUSIONS: Despite susceptibility artifacts caused by iron
      deposits, we demonstrated EEG-fMRI responses involving the perilesional areas in
      33% of studies. We also demonstrated diffuse rather than focal responses, in
      accordance with previous studies in lesional and non-lesional temporal lobe
      epilepsy, confirming the frequent distant effect of epileptic spikes.

PMID- 17000082
TI  - Dietary glucosylceramide improves skin barrier function in hairless mice.
AB  - BACKGROUND: Sphingolipids are known to play an important role in both water
      retention and epidermal permeability barrier function in mammalian stratum
      corneum. However, little is known about the effects on epidermal function of
      orally administered sphingolipids. OBJECTIVE: We examined the effect of dietary
      glucosylceramide (GluCer) on the maintenance and recovery of epidermal barrier
      function. METHODS: Hairless mice were fed a particular diet (HR-AD) for 4 weeks
      to induce chronic skin perturbation. Subsequently, a normal diet supplemented
      with GluCer (from rice bran and germ) was provided for the next 4 weeks.
      Transepidermal water loss (TEWL) and stratum corneum flexibility were measured
      throughout this recovery phase. Additional hairless mice were fed a diet with or
      without a maize-extracted GluCer supplement for 5 weeks, then their skin was
      acutely perturbed with repeated tape-stripping, and the TEWL was measured.
      RESULTS: Although skin functions were generally lower following chronic
      perturbation, in GluCer-fed mice the TEWL was significantly reduced at 2 weeks
      and the stratum corneum flexibility was increased at 3 weeks compared to
      controls. Following acute barrier perturbation by tape-stripping, mice an HR-AD
      fed a GluCer diet exhibited enhanced recovery compared with the control diet
      group. CONCLUSION: These results demonstrate that in hairless mice skin barrier
      functions impaired by chronic or acute perturbations were improved by dietary
      GluCer. The oral administration of GluCer may be useful for the preservation and
      recovery of epidermal barrier functions an HR-AD.

PMID- 17000083
TI  - Immunocyto- and histochemical profiling of nucleostemin expression: marker of
      epidermal stem cells?
AB  - BACKGROUND AND OBJECTIVE: Because the nucleolar protein nucleostemin is present
      in bone marrow and neuronal stem cells and malignancies originating thereof we
      monitored its expression in frozen sections from normal human epidermis, basal
      cell carcinomas, cultured keratinocytes and cells of the squamous carcinoma line
      FaDu. In addition, probing the value of this protein as a marker of epidermal
      stem cells was an aim of this study. MATERIALS AND METHODS: To further
      characterize cell features we added analysis of expression of keratins 10 or 19
      as markers of terminal differentiation and Ki67 as marker of proliferating cells
      as well as three adhesion/growth-regulatory galectins. RESULTS:
      Immunohistochemical monitoring revealed expression of nucleostemin in cells of
      both Ki67-positive and -negative nuclei regardless of the K10-expression status.
      Cultured keratinocytes were positive, when they were prepared from hair follicles
      and cultured in the presence of feeder cells. A small population of these
      nucleostemin-positive cells also expressed galectin-1 but not galectins-3 and -9
      in their nucleoli. Part of these cells also expressed keratin 19. FaDu cells were
      strongly positive, illustrating expression in malignant cells which require no
      feeder layer. Of note, the number of galectin-1-positive nucleoli was reduced in
      the course of culture. CONCLUSION: Nucleostemin positivity cannot be considered
      as marker for stem cells in skin sections. In cultured cells, nucleostemin is
      expressed in a distinct population of the epidermal cells from hair follicle kept
      in the presence of a feeder layer, intimating an association of nucleostemin
      expression with this type of epithelio-mesenchymal interaction which is not
      essential during propagation of malignant cells.

PMID- 17000084
TI  - Characterisation of the main clones of Streptococcus pyogenes carrying the ermA
      (subclass TR) gene in Spain.
AB  - Seventy-four Streptococcus pyogenes isolates showing the macrolide-lincosamide
      streptogramin B (MLS(B)) resistance phenotype carrying the ermA gene (72 of which
      showed the inducible resistance phenotype) were obtained between 1999 and 2004.
      Seven different sequence types (STs) and emm types were detected: emm22/ST46
      (n=33); emm77/ST63 (n=22); emm73/ST331 (n=10); emm94/ST89 (n=6); and one isolate
      each of emm28/ST52, emm11/ST403 and emm4/ST38. All ST46 isolates were susceptible
      to tetracycline and almost all reacted against the T12 type (all agglutinated
      into the T-pattern 3/12/13/B3264). Resistance to tetracycline was observed in all
      ST63 (tetO+) and ST89 (tetM+) isolates. Most of the ST63 isolates reacted against
      the T28 type (all agglutinated into the T-pattern 9/13/28). The 74 isolates were
      grouped into eight pulsed-field gel electrophoresis pulsotypes (one cluster for
      each emm/ST type, except for emm77/ST63).

PMID- 17000085
TI  - Antibiotic resistance of urinary tract pathogens and evaluation of empirical
      treatment in Turkish children with urinary tract infections.
AB  - The changing pattern of antimicrobial resistance in the causative microorganisms
      of urinary tract infection (UTI) in childhood is a growing problem. The aims of
      this study were to assess the resistance patterns of urinary isolates to commonly
      used antimicrobials and to evaluate the options for empirical treatment of UTI. A
      prospective cross-sectional analysis of bacteria isolated from children with UTI
      was performed between January 2003 and January 2004. Resistance to antibiotics
      was analysed in three age groups: Group I, < or =12 months; Group II, 13-60
      months; and Group III, >60 months. A total of 165 urinary pathogens were isolated
      from 131 patients. Mean patient age was 63.7+/-49.8 months. The most common
      causative agent was Escherichia coli (87% of cases) followed by Klebsiella
      pneumoniae (10%). Resistance to ampicillin (74.2%) and co-trimoxazole (61.3%) was
      significant in all isolates. Nitrofurantoin was the most active agent against E.
      coli (2.2% resistant isolates), followed by amikacin (4.9%), ceftriaxone (7.5%)
      and ciprofloxacin (12%). None of the isolates from Group I patients were
      resistant to ciprofloxacin and a low resistance rate (7.1%) was noted for
      amikacin. In Group II patients, none of the isolates were resistant to amikacin,
      and ceftriaxone was the second most suitable antibiotic (resistance rate 2.2%).
      In Group III patients, the lowest resistance rate was against nitrofurantoin
      (2.7%). In conclusion, we observed that the use of ampicillin and co-trimoxazole
      as a single agent for empirical treatment of a suspected UTI would not cover the
      majority of urinary pathogens in our region. Whilst amikacin, with a negligible
      resistance rate, was suitable in all age groups, gentamicin might still be useful
      as an empirical treatment of UTI in children aged >1 year. Nitrofurantoin could
      be included as a reasonable alternative in the empirical treatment of lower UTI
      in older children.

PMID- 17000086
TI  - Nosocomial spread of QnrA-mediated quinolone resistance in Enterobacter
      sakazakii.

PMID- 17000087
TI  - Genetic stability of class 1 integron-borne blaGES-type genes under short-term in
      vitro antibiotic stress.

PMID- 17000088
TI  - The neural correlates of habituation of response to startling tactile stimuli
      presented in a functional magnetic resonance imaging environment.
AB  - Functional magnetic resonance imaging (fMRI) provides a means of identifying
      neural circuitry associated with startle and its modulation in humans. Twelve
      subjects who demonstrated eyeblink startle in the laboratory were recruited for
      an fMRI study in which they were scanned while presented with two identical runs
      consisting of alternating blocks of no stimuli and startling tactile stimuli.
      Together, behavioral and imaging data are consistent with a pattern of general
      cortical and thalamic activation induced by startling stimuli that shows
      habituation both across and within runs. From Run 1 to Run 2, both the eyeblink
      amplitude and the fMRI signal decreased. Within Run 1, there was a graded
      decrease in eyeblink amplitude and whole-brain fMRI signal across blocks of
      startling stimuli. A similar graded decrease was observed in the thalamus signal,
      as well. Thus, startling tactile stimuli initially induce widespread cortical and
      thalamic activity, perhaps mediated by the reticular activating system. The
      activity then habituates in a graded fashion with repeated presentations of the
      stimuli.

PMID- 17000089
TI  - Novel transmucosal absorption enhancers obtained by aminoalkylation of chitosan.
AB  - Literature data suggest that quaternized chitosans have a transmucosal drug
      absorption enhancing property depending on their MW, quaternization degree and
      other structural features. With the purpose of preparing novel effective
      promoters, a chitosan (Ch) from crab shell (ChC; viscometric MW, 800 kDa;
      deacetylation: 90%, IR; 84%, NMR) and one from shrimp shell (ChS; viscometric MW,
      590 kDa; deacetylation: 90%, IR; 82%, NMR) were reacted with 2-diethylaminoethyl
      chloride (DEAE-Cl) and novel derivatives containing different percentages of
      pendant quaternary ammonium groups were obtained. NMR analysis, based on HSQC,
      COSY, TOCSY and ROESY maps, indicated that three partially substituted N,O-[N,N
      diethylaminomethyl(diethyldimethylene ammonium)(n)]methyl chitosans, coded N(+)
      ChS-2 (degree of substitution, DS=40%; n=1.6), N(+)-ChS-4 (DS=132%; n=2.5), and
      N(+)-ChC-4 (DS=85%; n=1.7) resulted from the reaction, depending on whether the
      DEAE-Cl/Ch repeating unit molar ratio, was 2:1 or 4:1. The effects of the
      derivatives on the permeability of rhodamine 123 (Rh-123), hydrophobic, marker of
      the transcellular absorption route, and of fluorescein sodium (NaFlu), polar,
      marker of the paracellular route, across excised porcine cheek epithelium were
      assessed, using Franz type diffusion cells. Rh-123 permeability was enhanced by
      N(+)-ChS-4 (enhancement ratio, ER=8.4) and by N(+)-ChC-4 (ER=3.9), whereas N(+)
      ChS-2 was ineffective. NaFlu permeability was enhanced by N(+)-ChS-2 (ER=7.2),
      N(+)-ChS-4 (ER=7.4) and N(+)-ChC-4 (ER=6.6). In conclusion, the three
      derivatives, whichever their DS, promote paracellular transport, while
      transcellular transport is substantially accelerated only by the most substituted
      one.

PMID- 17000090
TI  - Degradable gene carriers based on oligomerized polyamines.
AB  - The focus of this work was to develop potentially biodegradable, polycationic
      gene carriers possessing high efficiency for gene delivery and being essentially
      non-toxic. A library of 37 soluble polycations was synthesized by oligomerization
      of low molecular weight oligoamines with three different crosslinkers, dithiobis
      succinimidyl proprionate, dimethyl dithiobis-propionamidate, and hexanediol
      diacrylate. The types of oligoamine and crosslinker influenced biophysical
      properties such as DNA binding, hemolytic and endosomolytic membrane activity,
      transfection efficiency and cytotoxicity of the gene carrier. Degradability of
      polymers based on reductive cleavage of disulfide bonds or ester hydrolysis was
      demonstrated. Within the library, oligoethylenimine (800 Da)-based polymers
      showed the highest gene transfer efficiencies and exceeded the golden standard
      linear polyethylenimine (22 kDa) in terms of activity/toxicity profile.

PMID- 17000091
TI  - Effects of paclitaxel, docetaxel and their combinations on subcutaneous lymphomas
      in inbred Sprague-Dawley/Cub rats.
AB  - We investigated, whether the effects on paclitaxel, docetaxel or their
      combinations on T-cell lymphomas in Sprague-Dawley/Cub rats were mainly caused by
      their different efficiency or combination of different mechanism of action, or
      limited by metabolic inactivation by P450 enzymes or drug efflux caused by P
      glycoprotein (P-gp). Docetaxel most effectively prolonged the survival of rats
      and the time of lymphoma appearance, inhibited their intravital size and weight
      after sacrifice. Paclitaxel was poorly effective and combined administration had
      intermediate effects. Blood levels of both drugs were similar. Repeated
      administration of paclitaxel, but not docetaxel, decreased its area under
      concentration, but the effect disappeared 6h after dosing and was not sufficient
      to explain lower effects of paclitaxel. The faster metabolism of docetaxel than
      paclitaxel in vitro did not limit its higher efficiency and repeated
      administration of paclitaxel did not induce its metabolism to decrease its blood
      levels sufficiently. Likewise, undetectable expression of P-gp protein in tumours
      could not explain lower effects of paclitaxel, which is a better substrate of P
      gp. Docetaxel was three-fold more effective than paclitaxel against P388D1
      lymphoma cell line, used as a model of the T-cell lymphoma and combined action
      was dominated by the effects of docetaxel. Thus, docetaxel was effective against
      T-cell lymphomas and may be a potential anticancer drug in similar indications.

PMID- 17000092
TI  - Dynamic knowledge validation and verification for CBR teledermatology system.
AB  - OBJECTIVE: Case-based reasoning has been of great importance in the development
      of many decision support applications. However, relatively little effort has gone
      into investigating how new knowledge can be validated. Knowledge validation is
      important in dealing with imperfect data collected over time, because
      inconsistencies in data do occur and adversely affect the performance of a
      diagnostic system. METHODS: This paper consists of two parts. First, it describes
      methods that enable the domain expert, who may not be familiar with machine
      learning, to interactively validate knowledge base of a Web-based teledermatology
      system. The validation techniques involve decision tree classification and formal
      concept analysis. Second, it describes techniques to discover unusual
      relationships hidden in the dataset for building and updating a comprehensive
      knowledge base, because the diagnostic performance of the system is highly
      dependent on the content thereof. Therefore, in order to classify different kinds
      of diseases, it is desirable to have a knowledge base that covers common as well
      as uncommon diagnoses. RESULTS AND CONCLUSION: Evaluation results show that the
      knowledge validation techniques are effective in keeping the knowledge base
      consistent, and that the query refinement techniques are useful in improving the
      comprehensiveness of the case base.

PMID- 17000093
TI  - Death and decay in the trees of Mango (Mangifera indica L.).
AB  - Death and decay of trees of Mango (Mangifera indica L.) var. Kesar due to fungal
      infection was studied histologically. Fungal infection in the trees was observed
      due to various reasons like mechanical injuries in the stem, pruning of the
      branches, through the inflorescences, attack of Ambrosia beetle and termites. In
      the initial stage, fungal spores get settled on the flowers due to presence of
      nectar, followed by their germination and entry of the hypha into peduncle, which
      gradually spreads into younger branches. The inflorescences were first attacked
      by Fusarium moniliformis followed by other fungi like Alternaria, Chetomium sp.,
      Aspregillus ellipticus, Aspregillus niger, etc. Fungal mycelia gradually invade
      the xylem tissues from the top of the branches and spread basipetally ultimately
      causing death of the infected branches. During monsoon, the crevices on the
      surface of bark of the healthy plants supported the growth of fungi like
      Pleurotus, Auricularia, Xyleria, Daldinia sp., and Polyporous sp. The removal of
      bark from such infected trees revealed minute holes on the surface of the woody
      cylinder made by Ambrosia beetles. During wet season fungal mycelia makes an easy
      entry into the xylem through the wounded portion of the stem or pruned branches.
      Initial entry of the hyphae into xylem was seen through the ray cells. Then the
      hyphae enter into the lumen of axial elements lining the ray cells through pits
      and intracellular spaces. The vessel elements located in the xylem (transition
      zone) between healthy and infected portion were filled with tyloses while axial
      and ray parenchyma showed heavy accumulation of tannin contents. On the other
      hand, the infected xylem was also found devoid of reserve metabolites while in
      normal trees, axial and ray parenchyma showed heavy accumulation of starch
      grains.

PMID- 17000094
TI  - Profiling of prostanoids in zebrafish embryonic development.
AB  - Prostanoids (PG) play important roles in vascular, pulmonary, reproductive and
      renal physiology. Little is known about their roles in the embryonic development.
      Using the oviparous zebrafish embryo as a model, we determined the temporal
      expression of PGs synthesized from exogenous prostaglandin H(2). Prostaglandin
      E(2) is the major PG throughout first 120 h post-fertilization (hpf), whereas
      prostaglandin F(2)(alpha) is at a lower but also a constant level. Reverse
      transcription-polymerase chain reaction (RT-PCR) showed that transcripts of
      cytosolic and membrane-bound PGE synthases were evident during the 120 hpf
      period. Compared with thromboxane A(2), the level of prostacyclin (PGI(2))is
      higher at first 24 hpf, the stage before the formation of blood vessel. RT-PCR
      showed that transcript of prostacyclin synthase appeared at 7 hpf whereas
      thromboxane synthase appeared at 48 hpf, suggesting that PGI(2) has additional
      functions besides hemostasis. Interestingly, level of prostaglandin D(2) (PGD(2))
      followed an exponential decay over 120 hpf with a rate constant of 0.048 h(-1)
      and transcript of lipocalin-type PGD synthase was expressed at a higher level at
      early stage of development, suggesting that PGD(2) is highly regulated during
      embryogenesis.

PMID- 17000095
TI  - Parental smoking and lung function: misclassification due to background exposure
      to passive smoking.
AB  - We evaluated the role played by background exposure (i.e. exposure to
      Environmental Tobacco Smoke, ETS, from sources other than parental smoking) when
      evaluating the effect of parental smoking on lung function of adolescents. We
      performed a cross-sectional survey (937 adolescents) in the Lazio Region. Data
      were collected by a questionnaire, lung function tests and urinary cotinine to
      creatinine ratios (CCR) were measured. We found that 62.1% of subjects were
      exposed to current parental smoke. Among the 355 adolescents not exposed to
      parental smoke, a total of 92 (25.9%) had CCR levels greater than the median
      value of the distribution (17.3 ng/mg). Subjects with smoking parents had higher
      FVC and significant lower FEV(1)/FVC ratios than subjects without smoking
      parents. When "Background" ETS exposure was removed from the unexposed group by
      separately studying those without parental exposure but with CCR>17.3, results
      showed a reduction in lung function due to parental smoking which is greater
      compared to the previous model. Our study adds further evidence regarding the
      detrimental effect of ETS on lung function of adolescents. Negative results on
      the effect of parental smoking on lung function should be revisited if background
      exposure has not been considered in the analysis.

PMID- 17000096
TI  - The effect of bronchodilators and oxygen alone and in combination on self-paced
      exercise performance in stable COPD.
AB  - Both oxygen therapy and bronchodilators reduce exertional breathlessness and
      improve exercise tolerance in patients with stable chronic obstructive pulmonary
      disease (COPD). However their relative effectiveness and the value of their
      combined use on exercise performance has not been assessed. The effects of 5 mg
      of salbutamol plus 500 microg ipratropium bromide nebulisation followed by a 6
      min walking test while breathing O(2) were studied in a randomised, single-blind,
      placebo controlled, crossover trial in 28 patients with severe or very severe
      COPD, breathless on exertion and with oxygen saturation < or = 89% at rest or on
      exercise. Bronchodilator reversibility was minimal. The 6-min walking distance
      increased from 356 (128)m to 377 (117)m after the bronchodilator (P<0.05), to 406
      (109)m after supplementary oxygen but without bronchodilators (P 0.011 versus
      bronchodilators/air and 0.001 versus placebo/air), and to 430 (109)m after the
      combination of oxygen and the bronchodilators (P<0.0001 versus placebo/air and
      bronchodilators/air; P=0.014 versus placebo/oxygen). End-exercise dyspnea only
      fell significantly when oxygen and bronchodilator were combined. In severe or
      very severe COPD patients with relatively fixed airway obstruction
      bronchodilators enhance exercise performance obtained with oxygen. Clinically
      relevant improvement is possible when therapies with a different mechanism of
      action are combined.

PMID- 17000097
TI  - Elevated BALF concentrations of alpha- and beta-defensins in patients with
      pulmonary alveolar proteinosis.
AB  - Defensins are endogenous antibiotics and regulators of inflammation, immunity and
      wound repair. Their concentrations are substantially increased in bronchoalveolar
      lavage fluid (BALF) of patients with infectious lung diseases. alpha-defensin
      (HAD) levels are also elevated in patients with idiopathic pulmonary fibrosis
      (IPF) and correlated with the decline in pulmonary function tests, suggesting the
      association of defensins with the pathogenesis of interstitial lung diseases. The
      aim of this study was to determine the profile of defensins in interstitial lung
      diseases. Serum and BALF levels of HAD and beta-defensin 1 and 2 (HBD-1, and -2)
      were measured by radioimmunoassay in 63 patients with interstitial lung diseases,
      including idiopathic pulmonary alveolar proteinosis (PAP), IPF, nonspecific
      interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) and
      pulmonary sarcoidosis, and in 9 healthy volunteers as controls. Levels of HAD in
      BALF of patients with PAP were significantly higher than those in controls and
      patients with COP and sarcoidosis. Serum levels of HAD in all groups were
      significantly higher than those in controls. Levels of HBD-1 and -2 in BALF of
      patients with PAP were extremely high in all subjects. Serum levels of HBD-1 were
      higher in all patient groups, with the exception of those with PAP, and those of
      HBD-2 were also higher in patients with IPF and sarcoidosis, compared with
      controls. BALF of PAP patients, but not IPF patients and controls, expressed
      antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus.
      Our findings suggest different kinetics of HAD and HBD-1 and -2 in serum and BALF
      of interstitial lung diseases and that these antimicrobial peptides in the airway
      lumen may contribute to prevention of bacterial airway infections in PAP.

PMID- 17000098
TI  - Survey of early discharge schemes from the 2003 UK National COPD Audit.
AB  - BACKGROUND: Early discharge for patients with acute exacerbations of chronic
      obstructive pulmonary disease (AECOPD) has been shown to be effective by clinical
      trials. To evaluate its implementation and efficacy in clinical practice, data
      concerning early discharge schemes (EDS) from the 2003 National COPD Audit were
      collected and analysed. METHODS: All acute Trusts in the UK were surveyed in
      Autumn 2003 by two means: one a questionnaire relating to organisation of care
      and second an audit of 40 clinical cases admitted with AECOPD. RESULTS: Data were
      available for both organisation of care and clinical activity for 233 units, of
      which 103 (44%) had EDS. Models of care included admission prevention in the
      accident and emergency department (5%), rapid discharge in <48h (27%), assisted
      discharge occurring 2 days or more after admission (24%) and combinations of
      these (12%). There was wide variation in organisation of care overall. 30% of
      patients in units with EDS were discharged early from hospital. Units with EDS
      had an average LOS 1-day shorter with no increase in readmission rate (32% vs.
      32%) as for those without an EDS and no increase in mortality. CONCLUSIONS: There
      is wide variation in the availability of EDS for AECOPD in the UK, with
      increasing implementation of schemes. Thirty percent of patients can effectively
      be put into EDS which is higher than the figure of 25% from randomised controlled
      trials (RCTs). Mortality and readmission rates are the same as for units where no
      EDS is available and similar to results reported in RCTs. EDS therefore appears
      to be effective in routine clinical practice.

PMID- 17000099
TI  - Toward continuous glucose monitoring with planar modified biosensors and
      microdialysis. Study of temperature, oxygen dependence and in vivo experiment.
AB  - Glucose biosensors based on the use of planar screen-printed electrodes modified
      with an electrochemical mediator and with glucose oxidase have been optimised for
      their application in the continuous glucose monitoring in diabetic patients. A
      full study of their operative stability and temperature dependence has been
      accomplished, thus giving useful information for in vivo applications. The effect
      of dissolved oxygen concentration in the working solution was also studied in
      order to evaluate its effect on the linearity of the sensors. Glucose monitoring
      performed with serum samples was performed to evaluate the effect of matrix
      components on operative stability and demonstrated an efficient behaviour for 72
      h of continuous monitoring. Finally, these studies led to a sensor capable of
      detecting glucose at concentrations as low as 0.04 mM and with a good linearity
      up to 2.0 mM (at 37 degrees C) with an operative stability of ca. 72 h, thus
      demonstrating the possible application of these sensors for continuous glucose
      monitoring in conjunction with a microdialysis probe. Moreover, preliminary in
      vivo experiments for ca. 20 h have demonstrated the feasibility of this system.

PMID- 17000100
TI  - Electrochemical impedance spectroscopy for study of amyloid beta-peptide
      interactions with (-) nicotine ditartrate and (-) cotinine.
AB  - Immobilization of amyloid beta (Abeta) (1-40) peptide on Au-colloid modified gold
      electrodes has been studied. Colloidal Au was self-assembled onto gold electrodes
      through the thiol groups of 1,6-hexanedithiol monolayer. Next, buffered aqueous
      solution of Abeta (1-40) peptide existing in the beta-sheet structure in the
      acidic media was dropped on the electrode surface. Each step of electrode
      modification has been confirmed with cyclic voltammetry (CV) and electrochemical
      impedance spectroscopy (EIS). The changes of the resistance of the layer with
      deposited Abeta (1-40) peptide, occurred under stimulation by different
      concentration of (-) nicotine ditartrate and (-) cotinine were measured with EIS
      and were used for the calculation of association constants. The gentle measuring
      conditions applied in electrochemical impedance spectroscopy, together with
      suitable environment for biomolecules immobilization created by Au-colloid, might
      be recommended as the analytical tool for assessing the effectiveness of
      potential drugs used in Alzheimer's disease (AD) therapy.

PMID- 17000101
TI  - Metabolism and excretion of anabolic steroids in doping control--new steroids and
      new insights.
AB  - The use of anabolic steroids in sports is prohibited by the World Anti-Doping
      Agency. Until the 1990s, anabolic steroids were solely manufactured by
      pharmaceutical companies, albeit sometimes on demand from national sports
      agencies as part of their doping program. Recently the list of prohibited
      anabolic steroids in sports has grown due to the addition of numerous steroids
      that have been introduced on the market by non-pharmaceutical companies.
      Moreover, several designer steroids, specifically developed to circumvent doping
      control, have also been detected. Because anabolic steroids are most often
      intensively subjected to phase I metabolism and seldom excreted unchanged,
      excretion studies need to be performed in order to detect their misuse. This
      review attempts to summarise the results of excretion studies of recent additions
      to the list of prohibited steroids in sports. Additionally an update and insight
      on new aspects for "older" steroids with respect to doping control is given.

PMID- 17000102
TI  - Inhibitors of Plasmepsin II-potential antimalarial agents.
AB  - In order to overcome the problem of drug resistance in malaria, it appears wise
      to concentrate drug discovery efforts toward new structural classes and new
      mechanisms of action. We report our results, targeting Plasmepsin II, a
      Plasmodium falciparum aspartic protease active in hemoglobin degradation, a
      parasite specific catabolic pathway. The results show that the new structural
      class is not only inhibiting PMII in vitro but is also active in a P. falciparum
      infected human red blood cell assay.

PMID- 17000103
TI  - NC-100717: a versatile RGD peptide scaffold for angiogenesis imaging.
AB  - Targeting the molecular pathways associated with angiogenesis offers great
      potential in detecting disease pathology using in vivo imaging technologies.
      Initiation of angiogenesis requires activation and migration of endothelial cells
      in order for neovascularization to proceed. Endothelial cells associate with the
      extracellular matrix through specific interactions with a variety of cell
      adhesion receptors known as integrins. Peptides containing the tripeptide
      sequence RGD are known to bind with high affinity to the alphavbeta3 and
      alphavbeta5 integrins associated with angiogenesis. We present herein the
      synthesis and in vitro binding affinity of the RGD-containing peptide NC-100717
      and a range of molecular probes derived from this intermediate.

PMID- 17000104
TI  - Fish venom (Pterios volitans) peptide reduces tumor burden and ameliorates
      oxidative stress in Ehrlich's ascites carcinoma xenografted mice.
AB  - The present study was carried out to assess the effect of Pterios volitans venom
      (mixture of peptides) on Ehrlich's ascites carcinoma (EAC) and its influence on
      antioxidant status in the liver. Among six groups of albino mice, three were
      treated with sublethal doses of venom, along with the standard drug, 5
      fluorouracil. In EAC-bearing mice, mean life span and antioxidants were
      significantly decreased, whereas, body weight, tumor volume, viable tumor cell
      count, lipid peroxidation and expression of proliferating cell nuclear antigen
      were significantly increased. These changes were brought back to near normal in
      treatment groups. The findings are further confirmed by histopathological
      observations.

PMID- 17000105
TI  - Synthesis and SAR of 2-(4-fluorophenyl)-3-pyrimidin-4-ylimidazo[1,2-a]pyridine
      derivatives as anticoccidial agents.
AB  - Compounds 10a-10d and 10i are very potent inhibitors of Eimeria tenella cGMP
      dependent protein kinase (0.081-0.32 nM) and are very efficacious antiparasitic
      agents in vivo when administered to chickens at 12.5-25 ppm levels in the feed.

PMID- 17000106
TI  - Characterization of ATP-independent ERK inhibitors identified through in silico
      analysis of the active ERK2 structure.
AB  - The extracellular signal-regulated kinases (ERK1 and ERK2) are important
      mediators of cell proliferation. Constitutive activation of the ERK proteins
      plays a critical role in the proliferation of many human cancers. Taking
      advantage of recently identified substrate docking domains on ERK2, we have used
      computer-aided drug design (CADD) to identify novel low molecular weight
      compounds that interact with ERK2 in an ATP-independent manner and disrupt
      substrate-specific interactions. In the current study, a CADD screen of the 3D
      structure of active phosphorylated ERK2 protein was used to identify inhibitory
      compounds. We tested 13 compounds identified by the CADD screen in ERK-specific
      phosphorylation, cell proliferation, and binding assays. Of the 13 compounds
      tested, 4 compounds strongly inhibited ERK-mediated phosphorylation of ribosomal
      S6 kinase-1 (Rsk-1) and/or the transcription factor Elk-1 and inhibited the
      proliferation of HeLa cervical carcinoma cells with IC(50) values in the 2-10
      microM range. These studies demonstrate that CADD can be used to identify lead
      compounds for development of novel non-ATP-dependent inhibitors selective for
      active ERK and its interactions with substrates involved in cancer cell
      proliferation.

PMID- 17000107
TI  - Design, synthesis, and preliminary biological evaluation of novel ethyl 1-(2'
      hydroxy-3'-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate.
AB  - We synthesized a series of novel small molecules, ethyl 1-(2'-hydroxy-3'
      aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate derivatives 3a-3o, by the reaction
      of ethyl 3-aryl-1H-pyrazole-5-carboxylate with 2-aryloxymethylepoxide in the
      presence of potassium carbonate at refluxing in acetonitrile in moderate or
      excellent yields. We investigated the effects of all the compounds on A549 cell
      growth. The results showed that 15 compounds could suppress A549 lung cancer cell
      growth. Among them, compound 3i was the most effective small molecule in
      inhibiting A549 cell growth. Compound 3f might most effectively induce A549 cell
      differentiation. Compound 3g remarkably induced cellular vacuolation.

PMID- 17000108
TI  - Synthesis and evaluation of some lipidic aminoalcohols and diamines as
      immunomodulators.
AB  - Lymphoproliferation inhibition and cytotoxicity of a number of lipidic
      aminoacids, aminoalcohols and diamines were evaluated as a preliminary screening
      to select potential immunomodulators. The four most potent/less toxic compounds
      were submitted to delayed hypersensibility (DTH) assays to define the best to be
      evaluated further Graft-vs-Host, NO production and other immunoevaluation
      (CD4(+), CD45, CD8, CD11b, I-Ek, and NK cells) assays, to establish their
      immunomodulation potential for being further considered as auxiliary agents for
      vaccination against some parasitic infections. Compounds 5d, 6d, 6f, 7a, and 9a,
      fairly inhibited the lymphoproliferation (71.6-79.5%, at 3.2-2.4 nM), while the
      aminoalcohol derivative 6f and the diamine 7a gave the most promising results in
      the DTH assays. Diamine derivative 8b induced nitrite production on normal
      macrophages, whereas compounds 6f and 7a induced nitrite production on LPS pre
      stimulated macrophages. These two last compounds have been selected to follow in
      vivo vaccination assays.

PMID- 17000109
TI  - Synthesis and anti-HIV properties of new hydroxyquinoline-polyamine conjugates on
      cells infected by HIV-1 LAV and HIV-1 BaL viral strains.
AB  - To find new derivatives that block different virus strains entry in cells bearing
      specific surface receptors represent an interesting challenge for medicinal
      chemists. Here, we report the synthesis and the anti-HIV properties of a new
      series of analogues based on the introduction of quinoline moiety on various
      polyamine backbones, including polyazamacrocycles. Three compounds 7, 8, and 10
      of this series were found active on PBMCs cells infected by HIV-1 LAV or by HIV-1
      BaL, in contrast the well-known reference compound 1a (AMD 3100) was found only
      active on HIV-1 LAV strain.

PMID- 17000110
TI  - Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of
      5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-chloro-5
      fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to human isoform II.
AB  - The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the
      acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4
      thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic
      anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of
      the two compounds binds in the canonic manner to the zinc ion and interacts with
      Thr199, Glu106, and Thr200. The substituted phenyl tail of the second inhibitor
      was positioned in the hydrophobic part of the binding pocket, at van der Waals
      distance from Phe131, Val 135, Val141, Leu198, Pro202, and Leu204. These
      structures may help in the design of better inhibitors of these widespread zinc
      containing enzymes.

PMID- 17000111
TI  - Discovery of potent and selective inhibitors of 11beta-HSD1 for the treatment of
      metabolic syndrome.
AB  - High throughput screening efforts have identified a novel class of
      dichloroaniline amide 11beta-HSD1 inhibitors. SAR studies initiated from
      dichloroaniline 4 focused on retaining the potency and selectivity profile of the
      lead.

PMID- 17000112
TI  - Universal polyethylene glycol linkers for attaching receptor ligands to quantum
      dots.
AB  - Biologically active small molecule derivatives that can be conjugated to quantum
      dots have the promise of revolutionizing fluorescent imaging in biology. In order
      to achieve this several technical hurdles have to be surmounted, one of which is
      non-specific adsorption of quantum dots to cell membranes. Pegylating quantum
      dots has been shown to eliminate non-specific binding. Consequently it is
      necessary to develop a universal synthetic methodology to attach small molecule
      ligands to polyethylene glycol. These pegylated small molecules may then be
      conjugated to the surfaces of quantum dots. Ideally this universal strategy
      should be adaptable and be applicable to PEG chains of varying lengths. This
      paper describes the development of one such methodology and the synthesis of a
      pegylated derivative of the known 5HT(2) agonist 1-(2-aminopropyl)-2,5-dimethoxy
      benzene. This compound was tested and found to be an agonist for the 5HT(2A) and
      5HT(2C) receptor having EC(50) values of 250 and 50 nM, respectively.

PMID- 17000113
TI  - HPGe virtual point detector for radioactive disk sources.
AB  - Validity of the model of a virtual point detector (implying existence of a point
      where all interactions virtually occur) was confirmed for measurements of
      radioactive disk sources with HPGe detectors. The existing correlation of the
      count rates with the distance between the virtual plain detector and the detector
      face makes it possible to inter- and extrapolate calibration curves for disk
      radioactive sources for use at different source-detector face distances. The
      dependence of the distance between the virtual plane detector and the detector
      face on the photon energy was studied for sources of various radii.

PMID- 17000114
TI  - Ventricular myocardial band concept and ventricular resynchronization device
      therapy: Crossing the roads?

PMID- 17000115
TI  - Percutaneous radiofrequency thermal ablation of primary and metastatic lung
      tumors.
AB  - OBJECTIVE: Primary lung cancer is the leading cause of death from cancer. For
      patients with inoperable lung cancer, percutaneous radiofrequency thermal
      ablation (RFA) under CT-guidance represents a minimally invasive treatment. It
      can also be applied in combination with radiation therapy and chemotherapy.
      MATERIALS AND METHODS: In a period of 18 months, RFA under CT-guidance 27
      ablations were applied on 22 patients, 14 patients with primary lung cancer and 8
      patients with metastatic lung tumor. There were 15 men and 7 women ranging in age
      between 48 and 79 years. All patients were not surgical candidates either due to
      the advanced stage or due to comorbid diseases, while five denied surgery. The
      lesions' size was no bigger than 6 cm (range 1-6 cm) with an average of 3.8 cm.
      The diagnosis of all treated lesions was obtained with percutaneous biopsy under
      CT guidance. The procedure was performed under local anesthesia. RESULTS: There
      were no major complications observed, but a small pneumothorax and a minor
      hemoptysis in four cases, all conservatively treated. All patients were
      hospitalized for 24h. Follow-up was initially done in 1, 3, 6 and 12 months after
      RFA and it was accomplished by personal interview or by telephone call up to
      December 2005. Median progression free intervals were 26.4 months for primary
      lung cancer and 29.2 months for metastatic tumor. CONCLUSION: RFA is a minimally
      invasive technique that can be used as a palliative treatment in nonsurgical
      candidates with primary or metastatic lung tumor with a low morbidity and
      mortality.

PMID- 17000116
TI  - Regulation and expression of endothelin-1 (ET-1) and ET-receptors in rat
      epithelial cells of renal and intestinal origin.
AB  - The hormone endothelin-1 (ET-1) is involved in many functions of the kidney and
      intestine. In addition to its vasoactive and proliferative effects, ET-1 is
      involved in the maintenance of water and salt balance, and in drug excretion by
      influencing the activity of different transporters in the epithelial cells of
      these two organs. To study ET-1 function and its role in pathophysiological
      processes in epithelial cells in vitro, we investigated ET-1 and ET-receptor
      expression and inducibility of ET-1 excretion by cytokines in three rat cell
      lines of intestinal (IEC-6) and renal (NRK-52E and GERP) origin.
      Immunocytochemistry showed that all three cell lines express ET-1 and the ET-A
      and ET-B receptor. ET-1 was expressed intracellularly, and also the ET-A receptor
      showed a punctate intracellular staining pattern. The ET-B receptor was localized
      in the membrane, which was confirmed by Western blot analysis. Real-time RT-PCR
      and ELISA showed that exposure of IEC-6 cells to the cytokines, interleukin-1beta
      (IL-1beta) and tumor necrosis factor-alpha (TNFalpha), induced ET-1 mRNA
      expression and excretion, while IL-2 was ineffective. In NRK-52E cells, IL-1beta
      and TNFalpha induced ET-1 excretion as well. In GERP cells, adequate measurement
      of cytokine effects on ET-1 excretion was not possible, since ET-1 excretion
      under non-stimulated conditions was around the lowest level of detection. In
      conclusion, we showed ET-1 and ET-receptor expression, and inducibility of ET-1
      by cytokines in IEC-6, NRK-52E, and GERP cells. These rat intestinal and renal
      cell lines appear to be suitable for further characterisation of ET-1 function
      and its role in pathophysiological processes in epithelial cells.

PMID- 17000117
TI  - Interaction of Vimang (Mangifera indica L. extract) with Fe(III) improves its
      antioxidant and cytoprotecting activity.
AB  - A standard aqueous stem bark extract from selected species of Mangifera indica L.
      (Anacardiaceae)--Vimang, whose major polyphenolic component is mangiferin,
      displays potent in vitro and in vivo antioxidant activity. The present study
      provides evidence that the Vimang-Fe(III) mixture is more effective at scavenging
      2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals, as well as in
      protecting against t-butyl hydroperoxide-induced mitochondrial lipid peroxidation
      and hypoxia/reoxygenation-induced hepatocytes injury, compared to Vimang alone.
      Voltammetric assays demonstrated that Vimang, in line with the high mangiferin
      content of the extract, behaves electrochemically like mangiferin, as well as
      interacts with Fe(III) in close similarity with mangiferin's interaction with the
      cation. These results justify the high efficiency of Vimang as an agent
      protecting from iron-induced oxidative damage. We propose Vimang as a potential
      therapy against the deleterious action of reactive oxygen species generated
      during iron-overload, such as that occurring in diseases like beta-thalassemia,
      Friedreich's ataxia and haemochromatosis.

PMID- 17000119
TI  - Between session reproducibility and between subject variability of diffusion MR
      and tractography measures.
AB  - As diffusion tractography is increasingly used to generate quantitative measures
      to address clinical questions, it is important to characterise the inter-session
      reproducibility and inter-subject variability of these measures. Here, we assess
      the reproducibility and variability of diffusion tractography measures using
      diffusion data from 8 subjects scanned 3 times. We used probabilistic
      tractography to define the cingulum bundle, pyramidal tracts, optic radiations
      and genu of the corpus callosum in each individual data set using three different
      methods of seed definition. Measures of mean fractional anisotropy (FA) and mean
      diffusivity (MD) along the tracts were more reproducible than measures of tract
      volume. Further, tracts defined using a two region of interest (ROI) approach
      were more reproducible than those defined using manually placed seed masks alone.
      For mean FA taken from tracts defined using the two ROI approach, inter-session
      coefficients of variation (CV) were all below 5% and inter-subject CVs were below
      10%; for mean MD inter-session, CVs were all below 3% and inter-subject CVs were
      below 8%. We use the variability measures found here to calculate the sample
      sizes required to detect changes in FA, MD or tract volume of a given size,
      either between groups of subjects or within subjects over time. Finally, we
      compare tractography results using 60 diffusion encoding directions to those
      found using a subset of 12 directions; the number of diffusion directions did not
      have a significant effect on reproducibility, but tracts derived using fewer
      directions were consistently smaller than those derived using 60 direction data.
      We suggest that 12 direction data are sufficient for reproducibly defining the
      core of large bundles but may be less sensitive to smaller pathways.

PMID- 17000118
TI  - Reactive oxygen species modulate the differentiation of neurons in clonal
      cortical cultures.
AB  - Reactive oxygen species (ROS) are important regulators of intracellular
      signaling. We examined the expression of ROS during rat brain development and
      explored their role in differentiation using cortical cultures. High levels of
      ROS were found in newborn neurons. Neurons produced ROS, not connected with cell
      death, throughout embryogenesis and postnatal stages. By P20, ROS-producing cells
      were found only in neurogenic regions. Cells with low levels of ROS, isolated
      from E15 brains by FACS, differentiated into neurons, oligodendrocytes, and
      astrocytes in clonal cultures. Neurons produced high ROS early in culture and
      later differentiated into two types: large pyramidal-like neurons that fired no
      or only a single action potential and smaller neurons that expressed nuclear
      calretinin and fired repeated action potentials. Antioxidant treatment did not
      alter neuron number but increased the ratio of small to large neurons. These
      findings suggest that modulation of ROS levels influences multiple aspects of
      neuronal differentiation.

PMID- 17000120
TI  - Dynamic neuroimaging of retinal light responses using fast intrinsic optical
      signals.
AB  - Transient intrinsic optical responses associated with neural activation offer an
      attractive strategy for dynamic imaging of neural activity, and may provide a
      noninvasive methodology for imaging of retinal function. Here we demonstrate the
      feasibility of near infrared imaging of fast intrinsic optical changes in
      isolated frog retina activated by visible light. Using a photodiode detector in a
      transmitted light geometry, we routinely measured dynamic transmitted optical
      responses in single passes, at the level of one part in 10(4) of background
      light. Rapid CCD image sequences acquired with transmitted light (bright field)
      illumination disclosed larger fractional responses and showed evidence of
      multiple response components with both negative- and positive-going signals with
      different timecourses. Dark field imaging further enhanced the contrast and
      sensitivity of optical measures of neural activation. High-resolution imaging
      disclosed optical responses in single pixels often exceeding 5%, of background
      light, allowing dynamic imaging at the resolution of single cells, in single
      passes. Fast optical signals are closely related to identified response
      components of the electroretinogram. Optical responses showed complex but
      consistent spatial organization from frame to frame. Our experimental results and
      theoretical analysis suggest that the optical responses may result from dynamic
      volume changes corresponding to ion and water flow across the cell membrane,
      directly associated with the electrophysiological response.

PMID- 17000121
TI  - Regulation of class-switch recombination and plasma cell differentiation by
      phosphatidylinositol 3-kinase signaling.
AB  - Class-switch recombination (CSR) is essential for humoral immunity. However, the
      regulation of CSR is not completely understood. Here we demonstrate that
      phosphatidylinositol 3-kinase (PI3K) actively suppressed the onset and frequency
      of CSR in primary B cells. Consistently, mice lacking the lipid phosphatase,
      PTEN, in B cells exhibited a hyper-IgM condition due to impaired CSR, which could
      be restored in vitro by specific inhibition of PI3Kdelta. Inhibition of CSR by
      PI3K was partially dependent on the transcription factor, BLIMP1, linking plasma
      cell commitment and cessation of CSR. PI3K-dependent activation of the serine
      threonine kinase, Akt, suppressed CSR, in part, through the inactivation of the
      Forkhead Box family (Foxo) of transcription factors. Reduced PI3K signaling
      enhanced the expression of AID (activation-induced cytidine deaminase) and
      accelerated CSR. However, ectopic expression of AID could not fully overcome
      inhibition of CSR by PI3K, suggesting that PI3K regulates both the expression and
      function of AID.

PMID- 17000122
TI  - Toll-like receptor recognition regulates immunodominance in an antimicrobial CD4+
      T cell response.
AB  - Although Toll-like Receptors (TLRs) play a major function in innate recognition
      of pathogens, their role in antigen processing and presentation in vivo is poorly
      understood. Here we establish that Toxoplasma gondii profilin, a TLR11 ligand
      present in the parasite, is an immunodominant antigen in the CD4(+) T cell
      response to the pathogen. The immunogenicity of profilin was entirely dependent
      on both TLR11 recognition and signaling through the adaptor myeloid
      differentiation factor 88 (MyD88). Selective responsiveness to this parasite
      protein was regulated at the level of antigen presentation by dendritic cells
      (DC) and required both TLR signaling and major histocompatibility complex (MHC)
      class II recognition acting in cis. These findings support a major influence of
      TLR recognition in antigen presentation by DC in vivo and establish a mechanism
      by which TLR ligand association regulates the immunogenicity of microbial
      antigens.

PMID- 17000123
TI  - Antibiotic resistance in Propionibacterium acnes. Microbiological and clinical
      aspects.

PMID- 17000124
TI  - Band 3 (AE1, SLC4A1)-mediated transport of stilbenedisulfonates. I: Functional
      identification of the proton-activated stilbenedisulfonate influx site.
AB  - Stilbenedisulfonates (SD) bind to a "primary" SD (PSD) site on the outer membrane
      surface of band 3, and inhibit anion exchange (AE) allosterically. Yet, evidence
      [Membr. Biochem. 2 (1979) 297] suggests that SD can be transported by band 3,
      thus raising questions about the relative locations of the transport and SD
      binding sites. A "second" class of DBDS (4,4'-dibenzamido-2,2'
      stilbenedisulfonate) binding sites has been discovered, which is activated by
      protons (pK approximately 5.0), and is located on the membrane domain of band 3
      [Biochem. J. 388 (2005) 343]. Here we show that the "second" class of DBDS
      binding sites, not the PSD site, lies on the SD transport pathway. We compare the
      pH dependence of DBDS influx to DBDS binding using: (a) control cells, (b) cells
      selectively crosslinked at the PSD site by treatment with 300 microM BS3
      (bis(sulfosuccinimidyl)suberate), and (c) cells with DIDS (4,4'-diisothiocyanato
      2,2'-stilbenedisulfonate) bound covalently to the PSD site. DBDS binds to the
      "second" class of sites on band 3 in all three types of cells. DBDS does not bind
      to the PSD sites of BS3- or DIDS-modified cells. Proton-activated DBDS influx was
      observed using control and BS3-modified cells, but not when using DIDS-modified
      cells. The results with DIDS suggest that the PSD site and the transport site
      overlap. However, this interpretation is disproved by experiments with BS3
      modified cells, where the PSD site is blocked, yet DBDS transport and binding to
      the "second" class of sites both take place.

PMID- 17000125
TI  - Band 3 (AE1, SLC4A1)-mediated transport of stilbenedisulfonates. III: Role of
      solute and protein structure in proton-activated stilbenedisulfonate influx.
AB  - DBDS (4,4'-dibenzamido-2,2'-stilbenedisulfonate) influx into magnesium resealed
      ghosts (MRSG) occurs over the anion/proton co-transport pH range (pK
      approximately 5.0). Here, factors are studied which may influence the pH
      dependence of DBDS transport. Accumulation of various stilbenedisulfonate (SD)
      molecules was studied and found to be correlated with the hydrophobicity of the R
      groups (Hansch factor), not protonation of the sulfonates. The role of proton
      binding to glutamate 681 was found not to be part of the rate-limiting step in
      DBDS uptake by MRSG. Finally, the pH dependence of changes in quaternary
      structure/conformational state was investigated using an assay involving photo
      crosslinking of band 3 subunits in the presence of DASD (4,4'-diazido-2,2'
      stilbenedisulfonate). Lowering the pH promoted intersubunit crosslinking by DASD,
      with a pK value of 4.75+/-1.0. This value is comparable to the pK for DBDS
      binding to the "second" class of sites on control band 3 (pK = 5.01+/-0.16), and
      to DBDS influx into control MRSG (pK values between 4.57+/-0.15 and 4.7+/-0.1).
      Susceptibility to photo-crosslinking was reversed by raising the pH prior to
      initiation of the reaction. Significantly, no photo-crosslinking was observed
      between pH 6.0 and 8.0, where band 3 subunits are known to exist as stable dimers
      and tetramers. We conclude that intersubunit photo-crosslinking does not simply
      involve random collision between photo-activated DASD and band 3. Rather, proton
      binding to band 3 either alters the conformation at the interface between
      subunits of pre-existing tetramers, or it promotes self-association of stable
      dimers to a "novel" tetrameric conformational state.

PMID- 17000127
TI  - Interferon and ribavirin treatment results of patients with HBV-HCV co-infection
      cured of childhood malignancies.
AB  - OBJECTIVES: We aimed to investigate the virological and clinical characteristics
      and the results of combination therapy in six oncology patients with hepatitis B
      virus (HBV)-hepatitis C virus (HCV) co-infection. METHOD: Six patients (five male
      and one female; age range 8-14 years), diagnosed with HBV-HCV infections during
      follow-up at the oncology outpatient clinic during 2000-2001 were included in the
      study. They had received an average of 25.8 units of blood by transfusion per
      patient during their treatment for malignancies. Positive serological HBV
      indicators were determined 20-40 months after the end of chemotherapy. HCV RNA
      positivity was determined together with HBV at an average of 3.3 months after
      hepatitis B infection. Patients received interferon-alpha-2b and ribavirin for 12
      months. RESULTS: Both HBV DNA and HCV RNA became negative, and anti-HBe became
      positive in one patient. One patient had decreased HBV DNA levels and negative
      HCV RNA and HBeAg, but HBeAg became positive again at 18-months following
      treatment. Another patient had decreased serum HBV DNA and HCV RNA levels with
      normal ALT levels at the end of treatment; however, two months after therapy was
      ceased these values returned to pretreatment levels. CONCLUSION: We observed that
      combined treatment is effective in HBV-HCV infection. The effectiveness of
      combined treatment should be researched with larger groups of co-infected
      patients.

PMID- 17000128
TI  - [Drug addiction: A link between sexuality and maternal desire].
AB  - If addictions lead to a strategy in order to delay the access to adult sexuality,
      addiction to heroin satisfies some needs which annihilate one's own sexual
      desire. This investment in addiction reduces fertility because of the difficulty
      of drug-addict women to care of their body. A specific taking charge with the
      help of drug substitutes can lead to the introduction of a sponsorship for the
      future parents.

PMID- 17000129
TI  - Effect of material properties of composite restoration on the strength of the
      restoration-dentine interface due to polymerization shrinkage, thermal and
      occlusal loading.
AB  - The purpose of this investigation was to adopt an analytical approach to analyse
      stresses at the restoration-dentine interface caused by polymerization shrinkage,
      occlusal and thermal loading with the primary focus on evaluating the effect of
      the material properties of the composite restoration on the strength of the
      interface. Some essential simplifications were employed to derive an explicit
      analytical solution. The results confirm previous findings that interfacial
      stresses due to polymerization shrinkage are increased with the higher modulus of
      elasticity of the restoration, while Poisson's ratio of the restorative material
      has a very small influence on these stresses. Occlusal loading resulted in much
      lower interfacial stresses when compared to shrinkage and thermal loads. The
      obtained results were in a good agreement with other numerical and clinical
      studies. From the modelling analysis it was found that the majority of
      commercially available composite restorative materials are expected to create
      significant interfacial stresses when subjected to cold temperatures. In
      addition, it was shown that there is a considerable potential for interfacial
      stresses to be minimised by an appropriate selection of thermo-mechanical
      properties of the restorative material especially with the new finding on the
      negative temperature variation effect.

PMID- 17000130
TI  - Regulation of acetylcholinesterase expression by calcium signaling during calcium
      ionophore A23187- and thapsigargin-induced apoptosis.
AB  - We have recently reported that acetylcholinesterase expression was induced during
      apoptosis in various cell types. In the current study we provide evidence to
      suggest that the induction of acetylcholinesterase expression during apoptosis is
      regulated by the mobilization of intracellular Ca(2+). During apoptosis,
      treatment of HeLa and MDA-MB-435s cells with the calcium ionophore A23187
      resulted in a significant increase in acetylcholinesterase mRNA and protein
      levels. Chelation of intracellular Ca(2+) by BAPTA-AM (1,2-bis-(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester), an
      intracellular Ca(2+) chelator, inhibited acetylcholinesterase expression. A23187
      also enhanced the stability of acetylcholinesterase mRNA and increased the
      activity of acetylcholinesterase promoter, effects that were blocked by BAPTA-AM.
      Perturbations of cellular Ca(2+) homeostasis by thapsigargin resulted in the
      increase of acetylcholinesterase expression as well as acetylcholinesterase
      promoter activity during thapsigargin induced apoptosis in HeLa and MDA-MB-435s
      cells, effects that were also inhibited by BAPTA-AM. We further demonstrated that
      the transactivation of the human acetylcholinesterase promoter by A23187 and
      thapsigargin was partially mediated by a CCAAT motif within the -1270 to -1248
      fragment of the human acetylcholinesterase promoter. This motif was able to bind
      to CCAAT binding factor (CBF/NF-Y). These results strongly suggest that cytosolic
      Ca(2+) plays a key role in acetylcholinesterase regulation during apoptosis
      induced by A23187 and thapsigargin.

PMID- 17000131
TI  - Metformin does not prevent DNA damage in lymphocytes despite its antioxidant
      properties against cumene hydroperoxide-induced oxidative stress.
AB  - Metformin (1-(diaminomethylidene)-3,3-dimethyl-guanidine), which is the most
      commonly prescribed oral antihyperglycaemic drug in the world, was reported to
      have several antioxidant properties such as the inhibition of advanced glycation
      end-products. In addition to its use in the treatment of diabetes, it has been
      suggested that metformin may be a promising anti-aging agent. The present work
      was aimed at assessing the possible protective effects of metformin against DNA
      damage induction by oxidative stress in vitro. The effects of metformin were
      compared with those of N-acetylcysteine (NAC). For this purpose, peripheral blood
      lymphocytes from aged (n=10) and young (n=10) individuals were pre-incubated with
      various concentrations of metformin (10-50microM), followed by incubation with
      15microM cumene hydroperoxide (CumOOH) for 48h, under conditions of low oxidant
      level, which do not induce cell death. Protection against oxidative DNA damage
      was evaluated by use of the Comet assay and the cytokinesis-block micronucleus
      technique. Changes in the levels of malondialdehyde+4-hydroxy-alkenals, an index
      of oxidative stress, were also measured in lymphocytes. At concentrations ranging
      from 10microM to 50microM, metformin did not protect the lymphocytes from DNA
      damage, while 50microM NAC possessed an effective protective effect against
      CumOOH-induced DNA damage. Furthermore, NAC, but not metformin, inhibited DNA
      fragmentation induced by CumOOH. In contrast to the lack of protection against
      oxidative damage in lymphocyte cultures, metformin significantly protected the
      cells from lipid peroxidation in both age groups, although not as effective as
      NAC in preventing the peroxidative damage at the highest doses. Within the
      limitations of this study, the results indicate that pharmacological
      concentrations of metformin are unable to protect against DNA damage induced by a
      pro-oxidant stimulus in cultured human lymphocytes, despite its antioxidant
      properties.

PMID- 17000132
TI  - Comment on gas phase infrared spectrum and ab initio calculations of
      phosphorus(III) thiocyanide, SPCN.
AB  - We show that two of the three bands assigned to SPCN are assignable to cyanogen
      and that the bands assigned to SPCl are done so in error, with the 712 cm(-1)
      band in the spectrum of Allaf and Odeh assignable to HCN. There is no evidence
      for either ClPS or SPCN in the spectra shown. Finally low resolution IR
      spectroscopy by itself, whilst useful in assisting in the identification of
      pyrolysis products does not provide unambiguous identification and requires
      support by rigorous computation, band modelling and correct use of the
      literature. None of these are evidenced in the present paper of Allaf and Odeh
      nor indeed in the work that was the subject of our previous criticism and re
      analysis.

PMID- 17000133
TI  - Attention-deficit hyperactivity disorder involves differential cortical
      processing in a visual spatial attention paradigm.
AB  - OBJECTIVE: Inattention is undoubtedly one of the main characteristics of
      Attention-deficit hyperactivity disorder (ADHD). Nevertheless, a growing corpus
      of evidence shows that not all attentional processes are affected in this
      condition. This study aimed to explore the distribution of attentional resources
      in children with ADHD via a spatially shifted double-oddball visual task.
      METHODS: We recorded event-related potentials (ERPs) for all visual stimuli.
      Subjects were instructed to allocate attention in a specific area of visual space
      while ignoring all stimuli presented outside. Ten male children (age: 9-14; mean
      = 11.6 +/- 2.1) who met DSM-IV criteria for the ADHD combined subtype
      participated in the study, along with ten age- and sex-matched healthy controls
      (9-14; mean = 11.2 +/- 2.3). RESULTS: ADHD subjects showed late differential
      cortical responses to initially suppressed irrelevant stimuli. The amplitude of
      early N1-P1 components were mainly modulated by stimulus location and showed no
      significant differences between groups, but a late P300-like positivity was
      clearly evoked in the ADHD group by peripheral stimuli. CONCLUSIONS: These
      results suggest that ADHD may not compromise the early attentional spatial filter
      but rather entails a different distribution of attentional resources at later
      stages of cortical processing. Perhaps these differences may be attributable to
      individual differences in attentional mechanisms. SIGNIFICANCE: ADHD may not
      affect initial focusing of visual attention but rather the allocation of
      processing resources in later stages.

PMID- 17000134
TI  - A profile of sports science research (1983-2003).
AB  - A majority of sports science research is undertaken in universities and dedicated
      research centres, such as institutes of sport. Reviews of literature analysing
      and categorising research have been carried out, but categories identified have
      been limited to research design and data gathering techniques. Hence there is a
      need to include categories such as discipline, subjects and targeted sport. A
      study was conducted using document analysis method to gather data that described
      and categorised performance-based sports science research projects in Australian
      universities and institutes of sport. An instrument was designed that could be
      used by researchers to analyse and profile research in the area of sports
      science. The instrument contained six categories: targeted sport, primary study
      area, participant type, research setting, methodology and data gathering
      techniques. Research documents analysed consisted of 725 original unpublished
      research reports/theses. Results showed that over two-thirds of research projects
      were targeted to specific sports and, of this group, nearly half involved four
      sports: cycling, rowing, athletics and swimming. Overall, physiology was the most
      researched scientific discipline. The most frequently used research method was
      experimental design, and the most frequently used data gathering technique was
      physiological (performance) measures. Two-thirds of research was conducted in
      laboratory settings, and nearly half of the research was conducted with elite or
      sub-elite athletes as participants/subjects. The findings of this study provide
      an overall synopsis of performance-based sports science research conducted in
      Australia over the last 20 years, and should be of considerable importance in the
      ongoing development of sports science research policy in Australia.

PMID- 17000135
TI  - Knowledge acquisition and development of accurate rules for predicting protein
      stability changes.
AB  - Knowing the mechanisms by which protein stability change is one of the most
      important and valuable tasks in molecular biology. The conventional methods of
      predicting protein stability changes mainly focus on improving prediction
      accuracy. However, it is desirable to extract domain knowledge from large
      databases that is beneficial to accurate prediction of the protein stability
      change. This paper presents an interpretable prediction tree method (named
      iPTREE) that produces explanatory rules to explore hidden knowledge accompanied
      with high prediction accuracy and consequently analyzes the factors influencing
      the protein stability changes. To evaluate iPTREE and the knowledge upon protein
      stability changes, a thermodynamic dataset consisting of 1615 mutants led by
      single point mutation from ProTherm is adopted. Being as a predictor for protein
      stability changes, the rule-based approach can achieve a prediction accuracy of
      87%, which is better than other methods based on artificial neural networks (ANN)
      and support vector machines (SVM). Besides, these methods lack the ability in
      biological knowledge discovery. The human-interpretable rules produced by iPTREE
      reveal that temperature is a factor of concern in predicting protein stability
      changes. For example, one of interpretable rules with high support is as follows:
      if the introduced residue type is Alanine and temperature is between 4 degrees C
      and 40 degrees C, then the stability change will be negative (destabilizing). The
      present study demonstrates that iPTREE can easily be used in the application of
      protein stability changes where one requires more understandable knowledge.

PMID- 17000136
TI  - Gene therapy based on gemcitabine chemosensitization suppresses pancreatic tumor
      growth.
AB  - Excepting surgical resection, there is no efficient treatment against pancreatic
      cancer. The chemotherapeutic agent gemcitabine improves the patient's clinical
      status but survival is not prolonged. The aim of this study was to design a new
      strategy to render gemcitabine more efficient in the treatment of pancreatic
      cancer using gene therapy. We have generated a fusion gene (DCK::UMK) combining
      deoxycytidine kinase (DCK) and uridine monophosphate kinase (UMK), which converts
      gemcitabine into its toxic phosphorylated metabolite. Antitumor effects of
      DCK::UMK gene expression were tested in vitro and in vivo in an orthotopic
      transplantable model of pancreatic cancer established in hamsters. DCK::UMK
      sensitizes pancreatic cancer cells to gemcitabine by reducing dramatically both
      in vitro cell viability and in vivo tumor volume. We found that in vivo
      expression of DCK::UMK resulted in an antitumor bystander effect due to apoptosis
      of untransduced cells. In vivo intratumoral gene transfer of DCK::UMK using the
      synthetic carrier PEI induced a potent tumor regression. Taken together, the
      results show that the fusion gene DCK::UMK sensitizes pancreatic cancer cells to
      gemcitabine treatment to induce cell death by apoptosis and tumor regression.
      Intratumoral delivery of the DCK::UMK gene in combination with gemcitabine might
      be of high interest for pancreatic cancer management.

PMID- 17000138
TI  - Nucleotide usage, synonymous substitution pattern, and past recombination in
      genomes of Streptococcus pyogenes.
AB  - We examined (1) five variables summarizing nucleotide usage at synonymous sites;
      (2) pairwise patterns of nucleotide substitution among five genomes of
      Streptococcus pyogenes in order to examine the extent to which these variables
      are associated with past recombination events. Predicted prophage genes of
      MGAS10394 were characterized by an average pattern of nucleotide usage at
      synonymous sites that was distinct from that seen at most other genes. Ribosomal
      protein genes also showed a distinctive pattern, but one that differed from
      prophage genes in several key respects. The six most anomalous genes with respect
      to synonymous substitution in pairwise comparisons among the genomes included
      four prophage genes; these six genes were characterized by unusually high values
      of d(S), suggesting that these genes had different evolutionary histories from
      those of the other shared genes in the genome. This hypothesis was supported by
      phylogenetic analyses, which revealed phylogenies inconsistent with that of the
      majority of genes. Eighty-nine genes outside prophage regions were found to
      resemble prophage genes with respect to nucleotide content and the pattern of
      synonymous substitution, suggesting that these genes may have been involved in
      horizontal gene transfers. Although prophage genes do show distinctive patterns
      of nucleotide composition, the results indicated that those patterns were not in
      themselves sufficient to distinguish all known prophage genes from other genes.
      On the other hand, nucleotide content, when suitably measured, can form one of a
      set of biological indicators that can be used to identify candidate genes for
      horizontal gene transfer.

PMID- 17000137
TI  - Involving communities in the design of clinical trial protocols: the BAN Study in
      Lilongwe, Malawi.
AB  - OBJECTIVE: To learn the attitudes and concerns of the local community on
      participating in research, infant feeding practices, and maternal nutrition in
      order to inform the design of a clinical trial in Lilongwe, Malawi on the safety
      and efficacy of antiretroviral and nutrition interventions to reduce postnatal
      transmission of HIV. DESIGN: Formative research methods were used, including semi
      structured interviews, focus group discussions, home observations, and taste
      trials. Data were collected, analyzed, and incorporated into the protocol within
      3 months. RESULTS: Participants were supportive of the clinical trial, although
      their overall understanding of research was limited. Mothers agreed that infants'
      blood could be drawn by venipuncture, yet concern was raised about the amount of
      blood proposed to be collected from both infants and mothers. Data demonstrated
      that rapid breastfeeding cessation would be difficult and malnutrition could be a
      risk if infants were weaned early. Mothers selected a maternal supplement
      suitable for use in the clinical trial. CONCLUSIONS: The protocol was rapidly
      modified to achieve cultural acceptability while maintaining study objectives.
      Without the formative research, several significant areas would have been
      undetected and may have jeopardized the implementation of the trial. Additional
      research was carried out to develop a meaningful informed consent process, the
      amount of blood collected was reduced to acceptable levels, and the protocol was
      modified to reduce the risk of malnutrition. Researchers who conduct clinical
      trials are encouraged to incorporate formative research into their protocol
      design to ensure participant understanding of the research, to safeguard
      participants, and to increase feasibility and acceptance of the clinical research
      in the community.

PMID- 17000139
TI  - Quantification of fluorotelomer-based chemicals in mammalian matrices by
      monitoring perfluoroalkyl chain fragments with GC/MS.
AB  - Perfluorocarboxylic acids (PFCAs), namely perfluorooctanoic acid (PFOA) and
      perfluorononanoic acid (PFNA), have been identified as persistent,
      bioaccumulative and potentially toxic compounds. The structural analog, 8-2
      fluorotelomer alcohol (8-2 fTOH) is considered the probable precursor of these
      stable metabolites. Because simultaneous quantification is needed for volatile
      and non-volatile perfluorinated chemicals (PFCs) in complex matrices, a GC/MS
      method was developed and tested based on selected ion monitoring of
      perfluorinated alkyl parent chain fragment ions. Although the method requires a
      derivatization step, combined GC/MS analysis of PFCA-me's and FTOHs increases
      analytical efficiency and decreases sample analysis time. The method instrument
      detection limits are between 7.1 and 24.5 ng/mL extract (MTBE), and the method
      quantification limits are below 50 ng/mL serum or ng/g liver for all PFCs
      investigated. Recoveries from mouse serum and liver homogenates, which were
      spiked with FTOHs and PFCAs at levels of 25 and 200 ng/mL or ng/g, ranged from 81
      to 101%. Finally, the utility of the method was demonstrated by dosing male CD-1
      mice with 30 mg/kg-BW of 8-2 fTOH and quantifying PFCs 6h post-treatment. The
      advantages of this method are (1) the simultaneous detection of both volatile and
      non-volatile fluorotelomer-based chemicals in complex matrices, such as mammalian
      tissues, (2) as a confirmatory method to LC-MS/MS, and (3) as an alternative
      method of analysis for laboratories without access to LC-MS/MS.

PMID- 17000140
TI  - Separation of pectin methylesterases and polygalacturonases on monolithic
      columns.
AB  - The most abundant isoforms of tomato pectin methylesterase (PME; EC 3.1.1.11;
      M(r) 26 kDa), polygalacturonase (PG; EC 3.2.1.15; PG1 with M(r) 82 kDa) and a
      basic protein with M(r) 42 kDa and unknown function were isolated from fresh
      tomato fruit by a fast chromatographic procedure on a Convective Interaction
      Media (CIM) short monolithic disk column bearing carboxymethyl (CM) groups. The
      extraction of the targeted enzymes with 1.2M NaCl solution was followed by
      precipitation with ammonium sulfate at 60% of saturation, solubilisation of the
      pellet in 0.5M NaCl and fractionation using a linear gradient from 0 to 700 mM
      NaCl. Among six fractions five had PME activity and four had PG activity, while
      one fraction containing a pure protein with M(r) 42 kDa with neither of these
      activities. Two concentrated fractions, one with PG and one with PME were further
      purified. A linear gradient from 0 to 500 mM NaCl with 20% CH(3)CN in the mobile
      phase was used for the PG fraction and two CM disks and a linear gradient from 0
      to 200 mM NaCl were used for the PME fraction as a greater capacity was necessary
      in this case. From 4 kg of fresh tomato flesh we obtained 22 mg of purified PME,
      1.8 mg of purified, active PG1, 13.5mg of additional basic protein and a fraction
      with PG2 contaminated by a PME isoform. Carboxymethyl CIM disk short monolithic
      columns are convenient for semi-preparative and analytical work with tomato fruit
      pectolytic enzymes.

PMID- 17000141
TI  - Functional MRI of the newborn.
AB  - In order to provide accurate prognosis and developmental intervention to
      newborns, new methods of assessing cerebral functions are needed. The non
      invasive technique of functional magnetic resonance imaging (fMRI) can be
      considered as the leading technique for functional exploration of the infant's
      brain. Several studies have previously applied fMRI in both healthy and diseased
      newborns with different sensory and cognitive tasks. In this chapter, the
      methodological issues that are proper to the use of fMRI in the newborn are
      detailed. In addition, an overview of the major findings of previous fMRI studies
      is provided, with a focus on notable differences from those in adult subjects.
      More specifically, the functional responses and the localization of cortical
      activations in healthy and diseased newborns are discussed. We expect a rapid
      expansion of this field and the establishment of fMRI as a valid clinical
      diagnostic tool in the newborn.

PMID- 17000142
TI  - Current noise in transport of hydrophobic ions through lipid bilayer membranes
      including diffusion polarization in the aqueous phase.
AB  - An exact treatment of the current noise spectrum produced by transport of
      hydrophobic ions through membranes is presented, including the coupling of the
      diffusion processes through both the aqueous phase and the membrane. Both the
      equilibrium and the steady state noise spectra are computed. The theory contains
      previous results as limiting cases. The structure of the spectra is discussed
      with emphasis upon how noise measurements can be used to estimate kinetic
      parameters, especially the rate of desorption from the membrane. For this
      restricted model there is no low frequency divergence in the non-equilibrium
      current noise, i.e., for the model treated there is no 1/f noise.

PMID- 17000143
TI  - Noise-current generated by carrier-mediated ion transport at non-equilibrium.
AB  - The measured spectral intensity Sj(f) of noise-current generated by carrier
      mediated ion transport on bilayer membranes agrees under equilibrium and
      nonequilibrium conditions with the theoretically predicted behavior. It is shown
      that the shot noise intensity due to this ion transport mechanism yields a
      frequency independent level of Sj(f) at higher frequencies. The intensity of the
      shot noise contribution decreases with increasing voltage. Both experimentally
      and theoretically it could be shown that at nonequilibrium the Nyquist-theorem
      can no longer be applied for a description of the spectral intensity. Especially,
      the low frequency tail of Sj(f) is not proportional to the mean macroscopic
      steady state conductance. The transition of Sj(f) between the low and high
      frequency limit occurs in a frequency range which is related to the relaxation
      time constants of the transport system. In contrary to voltage jump current
      relaxation experiments where two relaxation times are predicted the theory
      predicts for the noise analysis a third relaxation time constant of a non-zero
      contribution to Sj(f). Besides the measurement of Sj(f) the corresponding
      autocorrelation function was determined. Comparison of both methods of noise
      analysis shows that for the carrier-mediated ion transport the determination of
      the autocorrelation function is the less appropriate approach due to principal
      methodical difficulties.

PMID- 17000144
TI  - Voltage dependencies of slow (ms) chemical relaxations.
AB  - The exponential-relaxation rates (rate constant k) of relatively slow (ms)
      chemical reactions may change with applied potential. Three general cases are
      described which, by their dependencies on an externally applied voltage, should
      be experimentally separable. They are processes due to (1) permanent dipoles
      entirely in the field - - (d In k)/d V proportional, variant V(2); (2) surface
      charge change - - (d In k)/d V proportional, variant V; and (3) charge transport 
      - dk/d V proportional, variant V (or a delay proportional to 1/V. The general
      analysis presented may be useful in analyzing biological electrical processes.

PMID- 17000145
TI  - Current fluctuations in discrete transport systems far from equilibrium.
      Breakdown of the fluctuation dissipation theorem.
AB  - A recently developed theoretical approach to transport fluctuations around stable
      steady states in discrete biological transport systems is used in order to
      investigate general fluctuation properties at nonequilibrium. An expression for
      the complex frequency dependent admittance at nonequilibrium is derived by
      calculation of the linear current response of the transport systems to small
      disturbances in the applied external voltage. It is shown that the Nyquist or
      fluctuation dissipation theorem, by which at equilibrium the macroscopic
      admittance or linear response can be expressed in terms of fluctuation properties
      of the system, breaks down at nonequilibrium. The spectral density of current
      fluctuations is decomposed into one term containing the macroscopic admittance
      and a second term which is bilinear in current. This second term is generated by
      microscopic disturbances, which cannot be excited by external macroscopic
      perturbations. At special examples it is demonstrated that this second term is
      decisive for the occurrence of excess noise e.g. the 1/f(2)-Iorentzian noise
      generated by the opening and closing of nerve channels in biological membranes.

PMID- 17000146
TI  - Dichroism and polarized fluorescence of chlorophyll a, chlorophyll c and
      bacteriochlorophyll a dissolved in liquid crystals.
AB  - Three photosynthetic pigments were studied: chlorophyll a, chlorophyll c and
      bacteriochlorcphyll a in nematic liquid crystal matrixes. The polarized
      absorption and fluorescence spectra as a function of the electric field have been
      measured. From the polarized components of the absorption A( parallel) and A(
      perpendicular) of the pigments in liquid crystals two reduced components A(x) and
      A(y) are calculated (x and y are the direction of the axis which is going through
      the second, fourth pyrrol rings, and the first, third rings, respectively). From
      these results the orientation of chlorophylls in liquid crystals and the
      configuration of the transition moments in the skeleton of the pigment molecules
      were determined.

PMID- 17000147
TI  - A 13C NMR spin-lattice relaxation study of the interaction of myelin proteins
      with lipid vesicles.
AB  - Natural abundance 13C nuclear magnetic spin-lattice relaxation times have been
      measured for bovine brain phosphatidylserine vesicles with and without bound
      proteins. The relaxation times were lower than published values for the
      corresponding nuclei in egg phosphatidylcholine, but showed the same trend, with
      relaxation times increasing along the acyl chains away from the polar headgroup.
      These times were inversely related to the degree of saturation of the lipid.
      Cytochrome c caused insignificant changes in the lipid acyl chain relaxation
      rates but reduced the resonance intensities, in agreement with Brown and Wuthrich
      (Biochem. Biophys. Acta 468 (1977) 389). In contrast, the basic protein from
      bovine myelin did not affect the intensities but reduced the relaxation times for
      13C nuclei near the bilayer centre, and for nuclei near carbon-carbon double
      bonds. These proteins also dramatically broadened the serine headgroup carboxyl
      resonance. It appears, in accord with other recent evidence, that the basic
      protein does penetrate the hydrophobic region of the bilayer (possibly to the
      centre), producing quantitatively similar changes in the relaxation rates to
      proteolipid protein, an integral membrane protein.

PMID- 17000148
TI  - Electrochemical behaviour of proteins at graphite electrodes. II.
      Electrooxidation of amino acids.
AB  - Electrochemical oxidation of L,alpha-amino acids at a paraffin-wax impregnated
      spectroscopic graphite electrode (WISGE) was studied by means of linear sweep,
      cyclic, phase-sensitive alternating current and differential pulse voltammetric
      techniques. It was found that out of the amino acids usually occurring in
      proteins only tyrosine, tryptophan, histidine, cystine, cysteine and methionine
      were oxidized at the WISGE. At relatively low concentrations of amino acids (up
      to ca. 2 x 10(-4) M) the electrode process in which the amino acids are oxidized
      at the WISGE has the characteristics of an irreversible reaction controlled by
      diffusion. Coulometric measurements showed that oxidation of tyrosine and
      tryptophan at the WISGE, i.e. of amino acids which are responsible for the
      oxidizability of proteins at graphite electrodes, is a two-electron process. At
      higher concentrations of tyrosine-and tryptophan (above ca. 2 x 10(-4) M)
      adsorption of the oxidation product of these amino adds was demonstrated.

PMID- 17000149
TI  - Evaluation of cooperativity for phase transitions in two- and three-dimensional
      systems.
AB  - Use of the so-called "cooperative unit" (readily obtainable from the midpoint
      slope of phase transition curves) is discussed for the determination of cluster
      sizes and cooperative interaction energies. This quantity has been commonly
      employed in a rather empirical way since its correct interpretation is known only
      for some special cases (linear systems, all-or-none transitions). It is shown in
      the framework of a lattice model (Ising model) that the cooperative unit may be
      interpreted in terms of correlation functions and that it defines an average
      cluster corresponding to the patch size as obtained from scattering experiments.
      Relations between the cooperative unit and a cooperativity parameter are given
      for various lattices. Different types of transition curves are discussed using a
      simple analytical formalism, the quasichemical approximation. Some important
      nonideality effects are investigated which may lead to a "smearing-out" of first
      order transitions.

PMID- 17000150
TI  - Aggregation of chlorophylls in monolayers. Part IV. The reorganisation of
      chlorophyll a in multilayer array.
AB  - The nature of the interaction between the chlorophyll a molecules in multilayer
      arrays obtained by the Langmuir-Blodgett technique is examined by electronic and
      infrared spectroscopies. Following the deposition of the multilayers, we observed
      a blue shift with time in the electronic spectra. This effect is monitored by
      infrared spectroscopy. The intensity of the coordinated ketone band is decreased
      while the intensity of the free ketone band is increased. These modifications are
      explained by the reorganization of the chlorophyll a molecules from an organized
      to a less organized one. The influence of H2O, D2O and SO2 vapors on the
      chlorophyll a multilayers give some informations on the role of water molecules
      in the aggregation of chlorophyll a in this ordered system. From these
      observations, a model is proposed for the multilayer arrangement implying two
      molecules of water per molecule of chlorophyll a.

PMID- 17000151
TI  - Analysis of various indefinite self-associations of the AK type.
AB  - Although we and others have developed equations to analyze for some indefinite
      self-associations that might be encountered, it is felt in some cases that these
      models, known as the sequential, equal equilibrium constant (SEK) models, might
      overestimate the size of aggregates encountered at higher solute concentrations.
      Thus, Garland and Christian proposed two attenuated equilibrium constant (AK)
      models that might overcome this problem. Their methods were restricted to ideal
      solutions and to osmometric procedures. We have removed these restrictions, and
      we have developed equations for analyzing four AK models that might be
      encountered. Various tests to aid in distinguishing these models are presented.
      These procedures have been tested with two simulated examples of a Type III AK
      indefinite self-association.

PMID- 17000152
TI  - Effects of dielectric saturation on planar electric double layers in salt
      solutions.
AB  - The effects of dielectric saturation on planar electric double layers in salt
      solutions are examined by solving the Poisson-Boltzmann equation analytically
      where the dielectric constant is given as a function of the electric
      displacement. The activity and the distribution of small ions, the surface
      potential and the Donnan potential are calculated. The salt exclusion parameter
      and the Donnan potential decrease while the surface potential increases as a
      result of the dielectric saturation. The electrostatic entropy is affected
      considerably by the dielectric saturation while the electrostatic energy is
      little influenced. Generally, the effects of dielectric saturation on the
      distribution of small ions and the thermodynamic properties are enhanced by the
      addition of salt.

PMID- 17000153
TI  - Statistical-mechanical theory of passive transport through partially sieving or
      leaky membranes.
AB  - The basic equations for multicomponent transport through partially sieving or
      leaky membranes are discussed from a statistical-mechanical viewpoint. They have
      the same mathematical form as the corresponding equations for open membranes, but
      differ in a discontinuous way from the equations for semipermeable membranes
      (since a "leak" in a semipermeable membrane constitutes a discontinuous or
      singular perturbation). Partially sieving membranes can be made to mimic
      semipermeable behavior through the introduction of characteristic time scales.
      They may approximate semipermeable behavior at short times, but always deviate at
      longer times.

PMID- 17000154
TI  - Metachromasy of crystal violet in the presence of poly(alpha-L-glutamic acid) and
      the bound-dye spectra determined by the principal/component-analysis method.
AB  - In order to study quantitatively the metachromatic behaviour of crystal violet
      (CV) in the presence of poly (alpha-L-glutamic acid), (poly (Glu)), four sets of
      the absorption spectra of the poly(Glu)-CV system were analyzed by the extended
      principal-component-analysis (PCA) method. Two classes of CV-Glu complexes, i.e.,
      the bound-CV species, are present in poly(Glu) regardless of its helical and
      random-coiled conformations over a wide range of the mixing ratios of Glu
      residues to CV (P/D). The spectra of the bound CV in a low P/D range < 100
      (complex I), extracted by the PCA method, are conformation-dependent showing
      three absorption bands at 506, ca. 550, and 610-620 nm. The spectra of the bound
      CV in a high P/D range > 100 (complex II) are closely related to, but not
      identical with, the free CV. The molar fractions of free CV and complexes I and
      II, evaluated in the P/D range of 0-150, indicate that CV binds more to the
      random-coiled poly(Glu) than to the helical one. Metachromasy of CV results from
      a complicated interplay of an unbound and two differently bound species.

PMID- 17000155
TI  - Concentration-dependent migration in gel chromatography of reversibly
      polymerizing solutes: the osmotic behavior of polyacrylamide gels.
AB  - The osmotic behavior of gels derived from polyacrylamide has been measured in
      order to establish the validity of assuming linear concentration dependence of
      bead shrinkage upon osmotic pressure in quantitative studies of reversibly
      associating solutes by gel chromatography on Bio-Gel. The concentration
      dependence of elution volume predicted with due allowance for this osmotic
      shrinkage yields theoretical curves that provide good descriptions of
      experimental results obtained in chromatography of alpha-chymotrypsin on Bio-Gel
      P-30 equilibrated with acetate-chloride buffer, pH 3-86, 10.20; and also of
      bacterial alpha-amylase on Bio-Gel P-150 equilibrated with 0.10 M NaCl-0.015 M
      calcium acetate-0.010 M EDTA, pH 7.0. For the former system the osmotic effect
      has negligible consequences on the quantitative interpretation of the results.
      With the alpha-amylase system, however, consideration of the osmotic effect is
      necessary to obtain even a qualitative indication of the existence of the monomer
      dimer equilibrium.

PMID- 17000156
TI  - A theory of the interaction between electrical double layers.
AB  - A generalization of the Poisson-Boltzmann approach to the repulsive electrostatic
      force between similar electrical double layers is presented. It is based on the
      integral equation formalism of the statistical mechanical theories of fluids and
      it is shown that the Poisson-Boltzmann result follows from a well-defined and
      improvable set of approximations.

PMID- 17000157
TI  - Transference numbers, polyion mobilities, and charge fractions in aqueous
      solutions of lithium, sodium, and potassium dextransulfate.
AB  - Results of Hittorf type transference number measurements are reported for aqueous
      solutions of lithium, sodium, and potassium dextransulfate (DS) in the
      concentration range 0.008-0.09 moles of sulfate groups per liter. The results for
      the polyion transference number are combined with equivalent conductance
      measurements reported earlier to calculate the polyion equivalent conductance,
      and the polyion charge fraction based on Wall's method. Our results show that the
      transference number of this high charge density polyion is larger than unity over
      the entire concentration range studied, and decreases monotonously with
      increasing concentration. The calculated charge fraction f of the polyion
      increases with increasing concentration, and at any concentration/decreases in
      the order LiDS > NaDS > KDS. A comparison between the conclusions derived from
      these transport experiments and from both mean and single ion activity
      measurements in dextransulfate solutions shows the considerable uncertainties
      involved in either of these methods, and emphasizes the need for the application
      of a variety of techniques, including spectroscopic techniques, to determine
      differential ion binding by polyions.

PMID- 17000158
TI  - Dielectric behavior of linear polyelectrolytes.
AB  - The dipolar correlation function for a system of counterions diffusing on the
      surface of a polyelectrolyte cylinder is computed. Repulsive coulombic
      interactions between the counterions are taken into account. Lateral dissociation
      and reassociation to the cylinder is treated microscopically. Numerical
      calculations needed to obtain quantitative results for the long time behavior are
      presented. The model dependence on its parameters is interpreted with special
      emphasis on parameter values typical of DNA.

PMID- 17000159
TI  - The binding of divalent metal ions to polyelectrolytes in mixed counterion
      systems. I. The dye spectrophotometric method.
AB  - The dye spectrophotometric method for the measurement of the activity of divalent
      metal ions in polyelectrolyte solutions containing added electrolytes is
      discussed. The method is applied to mixtures containing the dextransulfate
      polyanion, NaCl, and MgCl2 or Ca2. A two wavelength ratio method as applied to
      polyelectrolyte solutions is compared to the standard method which makes use of
      the previous determination of the dye-metal ion formation constant. The ratio
      method is found to be a convenient and reliable method which is not influenced by
      decomposition of the dye or by statistical errors in the extrapolation procedure.
      The activity coefficients as determined by the two wavelength dye
      spectrophotometric method are compared to results of Donnan exclusion
      measurements, and of EMF measurements using a calcium ion selective electrode.
      The results of the spectrophotometric method are equal to those of the two other
      methods within the limits of error in the latter. The spectrophotometric
      measurements can extend to much lower ion activaties than the other two methods,
      and can be done in the presence of a large excess of added electrolyte, yielding
      results of considerably improved precision when compared to Donnan and EMF
      methods.

PMID- 17000160
TI  - The binding of divalent metal ions to polyelectrolytes in mixed counterion
      systems. II. Dextransulfate-Mg2+ and dextransulfate-Ca2+ in solutions containing
      added NaCl or KCl.
AB  - Measurements of magnesium and calcium ion activities in solutions of the
      polyelectrolyte dextransulfate, with added sodium chloride or potassium chloride
      are presented. A two wavelength dye spectrophotometric method is used.
      Dextransulfate concentrations Cp (expressed as moles sulfate ion/litre) vary
      between 0.001 and 0.007, total ionic strengths between 0.005 and 0.08 mole/XXX.
      Divalent metal ion concentrations are varied between 0 and 1.2 Cp. The results
      for the metal ion activities are expressed in the form of parameters theta2 =
      C2/Cp (C(2bp) = bound divalent metal ion concentration) and K2 = theta2/(C2-C2b).
      For each divalent/univalent counterion pair the values obtained for theta2 and K2
      as a function of C2,Cp, and ionic strength are compared to predictions of the
      "two variable theory" developed for these mixed counterion systems by Manning.
      This comparison shows that the observed decrease in theta2 with increasing ionic
      strength at fixed C2 and Cp is generally well predicted by the two variable
      theory. The extent of divalent ion binding at a given C2, Cp, and ionic strength
      is largest for the Ca/Na counterion combination, and lowest for the Mg/K
      combination.

PMID- 17000161
TI  - Spectrophotometric determination of reaction stoichiometry and equilibrium
      constants of metallochromic indicators. I. General calculational method.
AB  - A calculational method is developed for spectrophotometric determination of
      stoichiometrics and individual equilibrium constants in the complexing of metal
      ions with metallochromic indicators. Implicit expressions are developed for the
      calculation of all parameters necessary to describe mixtures of 1 : 1, 1 : 2 and
      2 : 1 metal-indicator complexes. The analysis of titration curves entails a
      series of one-variable best-fit determinations based on mass action and
      conservation laws; this reduction in the number of degrees of freedom in the
      curve-fitting procedure yields greater resolution of the complexing parameters
      than is allowed by conventional methods. Since a common application of
      metallochromic indicators is to the determination of metal-binding properties of
      biological molecules, accurate description of metal-indicator complexing is vital
      for investigation of the regulatory roles of metal ions in biological events.

PMID- 17000162
TI  - Spectrophotometric determination of reaction stoichiometry and equilibrium
      constants of metallochromic indicators. II. The Ca2+-arsenazo III complexes.
AB  - The analytical method described in the preceding article was applied to
      spectrophotometric Ca2+-titrations of the metallochromic indicator arsenazo III
      (Ar). At various reactant concentrations it was determined that Ar forms 1:1,1:2
      and 2 : 1 complexes with calcium. The equilibrium constants and extinction
      coefficients at 602 nm were determined. Corrected to zero ionic strength at 293 K
      and pH 7.0, the reactions Ca + Ar = CaAr, CaAr + Ar = CaAr2 and CaAr + Ca = Ca2Ar
      are associated with dissociation equilibrium constants k(11) = 1.6 x 10(-6)M, K12
      = 3.2 x 10(-4)M and K21 = 5.8 x 10(-3)M. respectively. The extinction coefficient
      of unbound indicator is (602) = 9.6 (+/-0.3) x 10(3) cm(-1) M(-1). Arscnazo III
      complexes with monovalent ions like Na+ and K+ : at zero ionic strength, the
      dissociation constant of the Na+-Ar complex is about 0.1 M.

PMID- 17000163
TI  - On the inactivity of thiol-subtilisin. The role of the intramolecular electric
      field.
AB  - Based on computed proton affinities for several model systems, the energetics of
      proton transfer and the acidity of the catalytic triads Cys-His-Asn (papain). Cys
      His-Asp (thiol-subtilisin) and Ser-His-Asp (subtilisin) are discussed. It is
      shown that in papain the ion-pair Cys--HisH+ exists owing to the intramolecular
      electric field, and that a similar situation is found in thiol-subtilisin. but
      not in subtilisin. Assuming similar reaction mechanisms for papain and thiol
      subtilisin - i.e. proton transfer from HisH+ to the NH group of the scissile
      peptide bond - the inactivity of thil-subtilisin towards proteins is explained by
      the much greater basicity of His in the complex His-Asp- than in His-Asn. In
      order for this explanation to be consistent, it is tentatively concluded that the
      catalytic mechanism of the serine proteases is different from that of the cystein
      proteases, and involves direct transfer of the serine proton to the leaving group
      in the acylation step.

PMID- 17000164
TI  - Interaction of the ruthenium red cation with nucleic acid double helices.
AB  - The hexapositive complex cation ruthenium red very effectively stabilizes DNA and
      RNA double helices against thermal denaturation. In the presence of nucleic acid
      helices, this symmetric cation acquires an extrinsic CD spectrum near the
      wavelength of the dye's maximum absorbance. Competition experiments with single
      stranded polyd(T) show this induced CD to be the result of selective binding to
      helical sites. The preferential affinity of ruthenium red for double helical
      binding sites is so great that it brings about biphasic absorbance- temperature
      profiles of polyd(A-T) at low [cation]: [polynucleotide phosphate]. The visible
      CD signal and fraction of helix melting at the upper transition increases with
      ruthenium red concentration until approximate charge neutrality is reached. These
      interactions, which have been studied in detail with the poly(U-U) helix as well
      as polyd(A-T), are likely largely electrostatic, since sufficient [NaCl]
      eliminates the bipliasic melting of polyd(A-T), renders the ultraviolet
      absorbance of poly (U) insensitive to ruthenium red, and abolishes the induced CD
      effects. The bipliasic melting of polyd(A-T) at intermediate [dye] is attributed
      to saturation of remaining double helical segments by cation migration from newly
      melted regions- Furthermore, virtually no change was observed in the induced CD
      upon melting through the first transition, whereas the effect is destroyed upon
      inciting through the second transition. A quantitative treatment of the data is
      used to obtain binding site size and association constant for the complex. The
      induced effect may prove useful in the exploration of exposed nucleic acid
      helical structure in such complex particles as nucleosomes or ribosomes.

PMID- 17000165
TI  - The equilibrium constants and enthalpy changes for the esterification of glycine
      by ethanol in water and ethanol- water mixtures.
AB  - Equilibrium constants, defined on the basis of the moles of all reactants and
      products including water, were found to be 4.6, 1.0 and 0.8 for the
      esterification of the glycinc cation at 20 degrees in a dilute aqueous sytem, and
      systems having 0.5 : 1 and 1 : 1 molar ratios of ethanol to water, respectively.
      When corrections were made for deviations from ideality a value of 5 +/- 1 was
      obtained for all three systems. Enthalpy changes were determined calorimetrically
      for the dilute aqueous and equimolar ethanol-water systems, and in each case was
      close to 1 kcal mole(-). The entropy change was calculated as 6 cal mole(-1) deg(
      1).DeltaG(0') for the hydrolysis of the glycine ethyl ester cation at 20 degrees
      and pH 7 was calculated as -7.5 kcal mole(-1).

PMID- 17000166
TI  - Relation between differential pulse voltammetric oxidation of polyriboinosinic
      acid and its structure.
AB  - Electrooxidation of poly (I) at a paraffin wax-impregnated spectroscopic graphite
      electrode was studied by means of differential pulse voltammetry. It was found
      that the transition of single-stranded poly (I) to its multistranded form,
      induced by increasing the ionic strength of neutral medium, is accompanied by a
      lowering of the oxidation current of poly (I). The marked lowering of the
      oxidation current is also observable as a consequence of the formation of double
      stranded complex of poly (I). poly (C). The voltammetry at carbon electrodes
      provides for the study of poly(I) structure in principle identical information as
      optical methods.

PMID- 17000167
TI  - Mathematical modeling and computer simulation of isoelectric focusing with
      electrochemically defined ampholytes.
AB  - A mathematical model of isoelectric focusing at the steady state has been
      developed for an M-component system of electrochemically defined ampholytes. The
      model is formulated from fundamental principles describing the components'
      chemical equilibria, mass transfer resulting from diffusion and electromigration,
      and electroneutrality. The model consists of ordinary differential equations
      coupled with a system of algebraic equations. The model is implemented on a
      digital computer using FORTRAN-based simulation software. Computer simulation
      data are presented for several two-component systems showing the effects of
      varying the isoelectric points and dissociation constants of the constituents.

PMID- 17000168
TI  - The average number of distinct sites visited by a one-dimensional random walker
      and its application to isotope exchange in polypeptides.
AB  - The average number of distinct sites visited by a random walker moving with
      arbitrary transition probability on a one-dimensional lattice is calculated.
      Asymptotic forms of this quantity for both asymmetric and symmetric random walks
      are determined, and an exact solution for the latter case is also given for any
      number of steps. The average number of sites visited is then analyzed for
      intermediate numbers of steps by introducing an exponent. This approach is
      applied to explain the results of isotope exchange experiments in polypeptides,
      and applications of asymmetric random walks to other biological problems are
      briefly discussed.

PMID- 17000169
TI  - Interaction of some charged amphiphilic drugs with phosphatidylcholine vesicles.
      A spin label study of surface potential effects.
AB  - Adsorptions of amphiphilic drugs (propranolol, alprenolol, metoprolol and
      tetracaine) to phosphalidylcholine vesicles in media of different pH and NaCl
      concentrations have been studied. A positively charged spin label amphiphile, N,N
      di-methyl-N-nonyl-N-tempoylammoniumbromide, was used to follow the variation in
      the surface potential by ESR. Competition experiments between the probe molecule
      and the drugs were carried out. A spin-labeled analogue of propranolol was also
      employed. We have analysed the results in terms of the theory for the diffuse
      double layer (Gouy-Chapman) and treated various equilibrium models. A weak,
      specific adsorption of chloride ions was introduced. For the charged forms of the
      drugs simulations of the experiments by numerical solution of the system of
      equations in a satisfactory way furnished intrinsic binding constants,
      independent of surface potential effects. The common electrostatic surface
      potential is mainly ruling the competition, and not the number of surface
      vacancies.

PMID- 17000170
TI  - Dielectric behavior of polyelectrolytes II. The cylinder.
AB  - The dipolar correlation function for a system of coupterions diffusing on the
      surface of a polyelectrolyte cylinder is computed. The influence of screened
      coulombic repulsions on the dielectric increment is determined. Dissociation and
      reassociation of the counterions to the cylinder is treated microscopically and
      the coupled bulk diffusion is solved in the presence of the Poisson-Boltzmann
      potential. It is found that the correlation function contains a small, fast
      decaying, molecular weight independent part arising from diffusion around the
      cylinder and a large, slowly decaying, molecular weight dependent part arising
      from diffusion along the cylinder axis. The dissociation-reassociation kinetics
      can play a large, possible dominant, role in determining the relaxation rates.

PMID- 17000171
TI  - A laser-temperature-jump method for the study of the rate of transfer of
      hydrophobic ions and carriers across the interface of thin lipid membranes.
AB  - The first application of a laser-temperature-jump apparatus for the study of ion
      transport through planar (artificial) lipid membranes is described. The
      relaxation of the electric current is detected, either continuously at a constant
      applied voltage or discontinuously by a series of short voltage pulses. The
      second technique, a combined voltage- and temperature-jump method, is especially
      appropriate to investigate the kinetics of the adsorption/desorption process of
      hydrophobic ions and neutral carriers of cations at the membrane interface and to
      separate this phenomenon from the diffusion process through the unstirred aqueous
      layers adjacent to the membrane. The aim is to determine the rate-limiting step
      of transport. The permeation rate of the hydrophobic anion 2,4,6
      trinitrophenolate is limited by the inner membrane barrier. For tetraphenylberate
      the rate constant of translocation across the inner barrier and that of
      desorption from the membrane into water are found to be of comparable magnitude.
      The membrane permeability of the neutral macrocyclic ion carrier enniatin B is
      strongly interface limited by its comparatively small rate of desorption into
      water. These results show that the frequently used a priori assumption of
      partition equilibrium at the membrane interfaces during transport is not
      justified.

PMID- 17000172
TI  - Polarization of the ion atmosphere of a charged cylinder.
AB  - The dipole moment is calculated for an electric-field-induced polarization of a
      Debye-Huckel ion atmosphere surrounding a charged rod. If L is the length of a
      thin rod. Q is its linear charge density, Z is charge of the salt ion in
      solution, and k is the Debye-Huckel shielding parameter, then for KL less,
      similar 10, the calculated polarizability is proportional to
      Z(2)Q(2)L(1.8)/K(1.2). Comparison with experimental data for DNA shows that the
      ion atmosphere dipole is of the correct magnitude and is consistent with observed
      variations with Z, Q, L and k.

PMID- 17000173
TI  - Stabilization effect of protons and divalent cations on membrane structures of
      lipids.
AB  - Ordered-fluid phase transitions of methylphosphatidic and phosphatidic acid
      bilayers are discussed theoretically to explain comprehensively various observed
      data in the presence of Ca2+ or protons. It is shown that the observed data can
      be explained reasonably by taking account of the interaction among neighboring
      head-groups with the aid of Ca2+ or protons. As a result, a quantitative
      explanation is given for the dependence of the phase-transition temperature on pH
      as well as Ca2+ concentration with the coexistence of monovalent cations. The
      dependence of the cooperativity of the transition on pH and monovalent cation
      concentration is also well explained. It is also pointed out that in the ordered
      fluid phase transitions, a hysteresis metastable state and phase separation can
      be expected to appear under some conditions.

PMID- 17000174
TI  - Dielectric properties of spherical macroion suspensions. I. Study on monodisperse
      polystyrene latex.
AB  - Dielectric properties of polystyrene latex suspended in aqueous media are
      investigated with special attention to the effect of volume fraction of the latex
      and salt concentration. The experimental data show the existence of two
      dispersions, one in the low-frequency range from 10(3) to 10(5) Hz. and the other
      in the high-frequcncy range from 10(5) to 10(7) Hz. In the salt-free system. both
      dispersions are of the Debye type and their relaxation limes arc insensitive to
      the volume fraction. Addition of H2SO4 to the suspension enlarges the magnitude
      of the low-frequency dispersion and reduces that of the high-frequency
      dispersion. whereas it does not affect the relaxation times. In the mixture of
      two species of counterions, e.g. H+ and Na(+), the low-frequency dispersion
      deviates from the Debye type. while the high-frequency dispersion docs not. From
      these facts, the high- and low-frequency dispersions are thought to be due to the
      radial and tangential components of the displacement current at the surface of
      the latex. The latter process is consistent with the Schwarz theory of the
      dielectric dispersion of colloidal suspensions.

PMID- 17000175
TI  - A dye spectrophotometric method for binding studies of Zn2+ and Mn2+ by
      biopolyelectrolytes.
AB  - A dual-wavelength dye spectrophotometric method is reported for measuring zinc
      and manganese activities using the dyes tetramethylmurexide (TMMX) and murexide
      (MX) respectively. The method is applied to the measurement of the activities of
      these metal ions in solutions of the polyelectrolyte dextransulfate with added
      sodium chloride. Polyion concentrations, Cp (expressed as moles sulfate ion litre
      ) of 0.001 and 0.002 are studied at total ionic strengths 0.005, 0.0075, 0.01,
      0.02 and 0.03 mole/1. Divalent metal ion concentrations are varied between 0 and
      1.0 Cp. The results for the metal ion activities are expressed in the form of
      binding isotherms, theta2 versus C2/Cp (theta2 = C2b/Cp; C2b = bound divalent
      metal ion concentration) and Scatchard plots, K2 versus theta2/(C2-C2b), at
      different ionic strengths. The experimental data are correlated with the "two
      variable theory" eveloped for these mixed counterion systems by Manning. This
      comparison shows that the observed decrease in theta2 and K2 with ionic strength
      at fixed C2 and Cp is generally well predicted by the two-variable theory. Both
      Zn and Mn bind to the same extent to dextransulfate. This observation, and the
      reasonable agreement of the data with the "two-variable theory" may be
      interpreted as indicating a delocalized form of binding of these metal ions to
      the polymer.

PMID- 17000176
TI  - Single channel gating events in tracer flux experiments I. Theory.
AB  - Tracer ion flux measurements are a commonly used method for studying ion
      transport through membranes of cellular systems, where the rate of ion flow is
      determined by gating processes which control the opening and closing of
      transmembrane channels. Due to recent advances in the theoretical analysis of
      tracer flux from or into closed membrane structures (CMS), the mechanism of
      gating reactions can, in principle, be derived from flux data. A physically well
      founded analysis is presented for the dependence of the total tracer ion content
      of a collection of CMS on the gating processes. For functionally uncoupled gating
      units a mean single channel flux contribution [equation, see text] can be
      defined, where k is the intrinsic single channel flux coefficient, t the time
      over which flux is measured, and p(tau,t) is the probability that a given channel
      was open for a total period tau during t. This quantity reflects the mean time
      course of the tracer content due to flux through a single channel. Expressions
      for <e(-kt)> are derived that explicitly take into account a distribution in the
      lifetime of open channels. On the basis of the results, kinetic and thermodynamic
      parameters of multiphasic gating reactions can be determined from the time course
      of the overall tracer content in a colleciion of CMS.

PMID- 17000177
TI  - The release of monovalent counterions by addition of divalent countemons to
      aqueous solutions of maleic acid copolymer.
AB  - Divalent cation binding and the release of monovalent cations accompanying the
      cation binding were experimentally studied by ion-selective electrode methods in
      aqueous solutions of copolymer of maleic acid and ethyl vinyl ether. It was found
      that in the process of Ca2+ addition, all the Ca2+ added was bound to polyions
      and the initially condensed Na+ was released in proportion to the concentration
      of the added Ca2+ up to the critical concentration of added Ca2+ at which the
      condensation of Ca2+ ceases. Values of the structural charge density parameter
      xi(s), were determined from the end-points of condensation of Ca2+. The process
      of Na+ release by adding Ca2+ was analyzed on the basis of the counterion
      condensation theory by using these xi(s) values. In addition, the relationship
      between the activity coefficient gamma-- of Ca2+ and degree of neutralization
      alpha in salt-free solutions was obtained from the Manning theory. Agreement
      between the calculated and experimental values was excellent in both cases.

PMID- 17000178
TI  - The release of monovalent counterions by addition of divalent counterions in
      coulombic interaction system of polyions (II).
AB  - In this work, the increase in activity. Deltaa+ of a monovalent counterion (Na+)
      resulting from the addition or a divalent ion (Cu2+) was experimentally
      investigated in sulfate or sulfonate polyelectrolyte solutions. It was found that
      in the case of polyvinylsulfonate, a+ was expressed by Deltaa+ = Delta(C++ -a++).
      where C(++) and a(++) represent the molar concentration and activity of added
      Cu2+ respectively, while in the case of dextran sulfate, the expression or
      Deltaa+ became Deltaa+ =2Delta(C++-a++). Considering that interactions between
      these cations and sulfate or sulfonale groups are Durely electrostatic, these
      results were analyzed in relation to the conformation of the polyelectrolytes.

PMID- 17000179
TI  - Dependence on ionic strength of charge-induced coil-helix transition of sodium
      poly(L-glutamate) in aqueous solution.
AB  - Helix contents of sodium poly(L-glutamate) in aqueous NaCl solutions were
      estimated as functions of the degree of ionizalion, alpha. and the salt
      concentration by CD measurement. The helix content increases with increasing salt
      concentration but this helix stabilization decreases with decreasing alpha and at
      alpha<0.25 the helix conformation is destabilized by salt addition. The alpha
      dependence of the helix stabilization was qualitatively interpreted by Manning's
      theory in which electrostatic interactions between charges on alternatively
      arrayed coil and helix segments in a simplified polymer model were incorporated.

PMID- 17000180
TI  - Ionophore-catalyzed cation transport between phospholipid inverted micelles
      manifest in DNMR.
AB  - Studies of hyperfine shifts of lipid 31P resonances due to hydrated phospholipid
      inverted micelles in benzene are presented. Systems with distinct resonances from
      micelles containing no paramagnetic ions, and from micelles containing a single
      praseodymium(III) or a single europium(III) ion (and three nitrate counterions)
      have been generated. The addition of an ionophoric antibiotic from Streptomyces
      lasaliensis, lasalocid-A (X537A). causes both resonances to broaden and. with
      further additions, coalesce and eventually resharpen as a single line. Dilution
      of only the ionophore reverses these spectral changes. This is interpreted as a
      manifestation of dynamic NMR (DNMR. exchange broadening): i.e., that the
      ionophore catalyzes the equilibrium exchange of metal ions from micelle to
      micelle to the point where it becomes fast on the NMR time scale. This exchange
      is inhibited by protons or other competitive metal ions. We have simulated the
      spectra with a total lineshape analysis program and have thus extracted the
      average preexchange lifetimes for various concentrations of the antibiotic. We
      find a reasonably good first-order dependence on lasalocid-A concentration in
      each of several different experiments. This is in contrast to the higher order
      concentration dependences often observed by others using different techniques
      employing bilayer membranes. We favor a diffusional carrier mechanism involving
      surface aggregates of lasalocid-A for our process. This leads to the implication
      that a higher order concentration dependence found for a bilayer system arises
      from a different mechanism. The ionophore valinomycin does not catalyze rapid
      exchange in our system.

PMID- 17000181
TI  - Mathematical model for transient isoelectric focusing of simple ampholytes.
AB  - A mathematical model describing transient processes in isoelectric focusing (IEF)
      of L biprotic ampholytes is presented. The model is a generalization of our
      previous research on steady slate in IEF and consists of L nonlinear partial
      differential equations coupled with 2L+2 algebraic equations. Constraints imposed
      by the mode of operation, viz., constant current. voltage or power, are
      described. Due to the nonlinearity of the equations, analysis of the model
      requires computer simulation. Model equations suitable for computer
      implementation are derived.

PMID- 17000182
TI  - Assessing dietary intake: new ideas and better approaches.

PMID- 17000184
TI  - Improving taste sensation in patients who have undergone chemotherapy or
      radiation therapy.

PMID- 17000185
TI  - Do food frequency questionnaires have too many limitations?

PMID- 17000186
TI  - Getting that First Job: Tips for the Interview.

PMID- 17000187
TI  - Using the dietary reference intakes to assess intakes of groups: pitfalls to
      avoid.

PMID- 17000188
TI  - The food propensity questionnaire: concept, development, and validation for use
      as a covariate in a model to estimate usual food intake.
AB  - OBJECTIVE: Twenty-four-hour recalls capture rich information on food consumption,
      but suffer from inadequately measuring usual intakes of episodically consumed
      foods. We explore using food frequency questionnaire (FFQ) data as covariates in
      a statistical model to estimate individual usual intakes of episodically consumed
      foods and their distributions and describe the development of the Food Propensity
      Questionnaire, an FFQ introduced in the 2003-2004 National Health and Nutrition
      Examination Survey. DESIGN: We analyzed data from 965 adult participants in the
      Eating at America's Table Study who completed four 24-hour recalls and an FFQ. We
      assessed whether or not increasing FFQ-reported frequency was associated with
      both number of 24-hour recall consumption days and amounts reported. RESULTS: For
      52 of 56 food groups (93%), and 218 of 230 individual foods (95%), there were
      significant monotonically increasing relationships between FFQ frequency and 24
      hour recall probability of consumption. For 47 of 56 food groups (84%) and 55 of
      230 (24%) individual foods, there were significant positive correlations between
      FFQ frequencies and consumption-day mean intake. CONCLUSIONS: We found strong and
      consistent relationships between reported FFQ frequency of food and food-group
      consumption and probability of consumption on 24-hour recalls. This supports the
      premise that frequency data may offer important covariate information in
      supplementing multiple recalls for estimating usual intake of food groups.

PMID- 17000189
TI  - Effects of a stanol-enriched diet on plasma cholesterol and triglycerides in
      patients treated with statins.
AB  - BACKGROUND: Plant stanols have been recommended in combination with
      individualized dietary interventions to reduce plasma cholesterol concentrations.
      It is unclear whether plant stanols in combination with dietary guidance in
      patients already using optimal doses of statins will further reduce fasting and
      postprandial lipids compared with standard care. STUDY DESIGN: This single-blind,
      randomized study investigated the effect of plant stanols in margarines, combined
      with a lipid-lowering dietary intervention, in patients already on lipid-lowering
      medications at maximal doses not reaching their target lipid levels. Nutrition
      education was based on the stages of change theory. The control group (which
      served as the standard care control group) was also taking optimal doses of
      statins. This group received a margarine without plant stanols and a leaflet with
      Dutch nutrition guidelines. Fasting lipids were measured once in venous samples
      and postprandial lipemia was assessed by self-measured triglycerides in an
      outpatient setting. All subjects were given a capillary triglyceride measuring
      device (Accutrend GCT, Roche Diagnostics, Mannheim, Germany) and were instructed
      to measure their capillary triglycerides at six fixed time-points throughout the
      day on three different days. The mean area under the triglyceride curve
      represented total daylong triglyceridemia, which has been shown to reflect
      postprandial triglyceridemia. Twenty patients were included, 11 in the
      intervention group and 9 in the control group. RESULTS: In the plant stanol
      group, low-density lipoprotein cholesterol decreased significantly by 15.6%
      compared with a reduction of only 7.7% in the control group. The daylong
      triglyceridemia was similar in both groups at the beginning and at the end of the
      study, and no change was observed by the intervention. CONCLUSION: Intensive
      dietary intervention with addition of plant stanols results in clinically
      relevant reduction of low-density lipoprotein cholesterol in patients optimally
      treated with statins, compared with similar patients on statins receiving only
      standard care. The use of a plant stanol-enriched margarine did not decrease
      postprandial triglyceridemia in these patients.

PMID- 17000190
TI  - A new statistical method for estimating the usual intake of episodically consumed
      foods with application to their distribution.
AB  - OBJECTIVE: We propose a new statistical method that uses information from two 24
      hour recalls to estimate usual intake of episodically consumed foods. STATISTICAL
      ANALYSES PERFORMED: The method developed at the National Cancer Institute (NCI)
      accommodates the large number of nonconsumption days that occur with foods by
      separating the probability of consumption from the consumption-day amount, using
      a two-part model. Covariates, such as sex, age, race, or information from a food
      frequency questionnaire, may supplement the information from two or more 24-hour
      recalls using correlated mixed model regression. The model allows for correlation
      between the probability of consuming a food on a single day and the consumption
      day amount. Percentiles of the distribution of usual intake are computed from the
      estimated model parameters. RESULTS: The Eating at America's Table Study data are
      used to illustrate the method to estimate the distribution of usual intake for
      whole grains and dark-green vegetables for men and women and the distribution of
      usual intakes of whole grains by educational level among men. A simulation study
      indicates that the NCI method leads to substantial improvement over existing
      methods for estimating the distribution of usual intake of foods. CONCLUSIONS:
      The NCI method provides distinct advantages over previously proposed methods by
      accounting for the correlation between probability of consumption and amount
      consumed and by incorporating covariate information. Researchers interested in
      estimating the distribution of usual intakes of foods for a population or
      subpopulation are advised to work with a statistician and incorporate the NCI
      method in analyses.

PMID- 17000191
TI  - Development of a new instrument for evaluating individuals' dietary intakes.
AB  - OBJECTIVE: With the aim of developing a new dietary instrument for assessing an
      individual's usual intakes, we evaluated a hand-held personal digital assistant
      with camera and mobile telephone card, called Wellnavi (Matsushita Electric
      Works, Ltd, Osaka, Japan). SUBJECTS/SETTING: Twenty-eight college students
      majoring in food and nutrition in Okayama University of Japan voluntarily
      participated in this study. DESIGN: Applying a cross-sectional study design,
      participants were asked to keep 1-day weighed food records. Digital images of all
      recorded foods were obtained simultaneously and sent to registered dietitians by
      a mobile telephone card. The following day, a 24-hour recall was obtained. These
      procedures were repeated after 6 months. Participants' opinions about the three
      methods were determined using a questionnaire. STATISTICAL ANALYSIS: Differences
      in estimated median nutrient intake among the three methods were compared by
      Wilcoxon matched-pairs signed rank test. Relationships among the nutrient
      estimates by each method were evaluated using Spearman rank correlation
      coefficients. RESULTS: We found no significant differences between the Wellnavi
      method when compared with food records for most nutrients, except zinc,
      manganese, vitamin E, saturated fatty acid, polyunsaturated fatty acid, and
      dietary fiber. The median correlation coefficients for the nutrient estimates
      were 0.66 between the Wellnavi method and the food records. The survey showed
      that 57.1% of subjects considered the Wellnavi method the least burdensome of the
      three methods and the least time consuming (16 minutes) to record daily diet.
      About half of participants indicated that they would be willing to use the
      Wellnavi for 1 month to record their diet. CONCLUSIONS: This study suggests that
      a hand-held digital assistant may be a valid and convenient instrument for
      evaluating dietary intake.

PMID- 17000192
TI  - A diet quality index for American preschoolers based on current dietary intake
      recommendations and an indicator of energy balance.
AB  - OBJECTIVE: Based on current dietary intake recommendations and a recommendation
      to limit sedentary activity in preschoolers, an overall diet quality index for
      preschoolers (RC-DQI) incorporating a component for energy balance to measure
      adequacy of nutrition for growth, development, and disease prevention was
      developed. DESIGN/SUBJECTS: The newly developed index was used in nationally
      representative samples of 2- to 5-year-olds in the US Department of Agriculture
      Continuing Survey of Food Intakes by Individuals 1994-96 and 1998 (n=5,437).
      Index components included added sugar, total fat, polyunsaturated fatty acids,
      total and whole grains, fruits, vegetables, excess fruit juice, dairy, iron, and
      an interaction term of total daily energy intake and sedentary behavior
      (television time). Points were allocated to reflect deficient or excessive
      intakes. STATISTICAL ANALYSIS PERFORMED: Means and standard errors were used to
      describe food intakes and RC-DQI scores. Ability to differentiate diets was
      ascertained using mean intakes of food groups/nutrients followed by a
      nonparametric test of trends across ordered groups. Correlation coefficients
      measured dependence among RC-DQI components, nutrients, and overall energy
      intakes. Component scores of the highest and lowest quartile of RC-DQI were
      compared. RESULTS: Mean RC-DQI score was 64 points (range=28 to 93). Increasing
      RC-DQI scores were associated with improved diet quality. Children in the lowest
      RC-DQI quartile scored lower in all components. CONCLUSIONS: The RC-DQI
      successfully differentiated diets by level of diet quality. Increasing scores
      were associated with decreasing consumption of added sugar and juices, and
      increasing intakes of fiber, essential fatty acids, fruits, and vegetables. The
      RC-DQI can be used to determine diet quality in groups of preschool-age children.

PMID- 17000193
TI  - Correlates of fat intake behaviors in participants in the eating for a healthy
      life study.
AB  - OBJECTIVE: This study identified socioeconomic correlates of total dietary fat
      intake in the Eating for a Healthy Life Study, a community-based dietary
      intervention study involving religious organizations. SUBJECTS/DESIGN: To create
      our sampling frame for the Eating for a Healthy Life Study, a pool of religious
      organizations was identified from a list of religious faith organizations
      provided by the Church Council of Greater Seattle. Individual members were
      randomly selected from recruited religious organizations to complete a telephone
      administered, baseline, cross-sectional survey. There were 2,507 respondents who
      were eligible, consenting participants. Dietary behavior was assessed using a
      modified version of the Fat- and Fiber-Related Diet Behavior Questionnaire.
      Socioeconomic status was assessed using individual demographic variables. MAIN
      OUTCOME MEASURES: Fat-related behaviors indicated by fat summary score and stage
      of change. STATISTICAL ANALYSES: A multivariable linear regression model was used
      to examine the association of individual demographic variables with the Fat- and
      Fiber-Related Diet Behavior Questionnaire-derived measure of dietary fat intake.
      The same individual variables were used in a multivariable logistic regression
      model of dietary stage of change. RESULTS: Age, race, sex, education, and self
      assessed health status were found to be statistically significant correlates of
      fat intake. Variables associated with stage of dietary fat change included sex,
      education, and religious organization cohesion. CONCLUSIONS: Demographic variance
      is an important factor in understanding dietary fat intake.

PMID- 17000194
TI  - A novel dysphagia diet improves the nutrient intake of institutionalized elders.
AB  - OBJECTIVES: Dysphagia affects 35% to 60% of the institutionalized elderly
      population. This study aimed at evaluating the nutrient intake of frail
      institutionalized elderly persons with dysphagia and to assess the impact of
      Sainte-Anne's Hospital Advanced Nutritional Care program on dietary intake and
      weight. DESIGN: A 12-week intervention study. SUBJECTS/SETTING: Ninety-three
      individuals residing in a Montreal, Canada, long-term care facility who were aged
      at least 65 years were evaluated. Seventeen subjects with a body mass index (BMI;
      calculated as kg/m(2)) <24 or weight loss >7.5% within 3 months and with
      dysphagia were included. INTERVENTION: The treated group (n=8; aged 82.5+/-4.41
      years, weight 55.9+/-12.1 kg, BMI 22.4+/-3.93) received Sainte-Anne's Hospital
      reshaped minced- or pureed-texture foods with thickened beverages where required.
      The control group (n=9; aged 84.6+/-3.81 years, weight 54.3+/-7.49 kg, BMI 21.2+/
      2.31) maintained traditional nourishment. MAIN OUTCOME MEASURES: Macronutrient
      and micronutrient intake, weight, and BMI were measured at baseline, 6 weeks, and
      12 weeks. STATISTICS: Student t tests were performed to evaluate change within
      and between groups. RESULTS: The treatment and control groups were similar at
      baseline, having a mean age of 82.5+/-4.41 years vs 84.6+/-3.81 years and BMI of
      22.4+/-3.93 vs 21.2+/-2.31, respectively. The average weight in the treated group
      increased compared to the control group (3.90+/-2.30 vs -0.79+/-4.18 kg; P=0.02).
      Similarly, the treated group presented an increased intake of energy, proteins,
      fats, total saturated fats, monounsaturated fats, potassium, magnesium, calcium,
      phosphorus, zinc, vitamin B-2, and vitamin D compared to control subjects
      (P<0.05). CONCLUSION: Institutionalized elderly patients with dysphagia can eat
      better and increase body weight via a diversified, modified in texture, and
      appealing oral diet that meets their nutrition needs.

PMID- 17000195
TI  - School vending machine use and fast-food restaurant use are associated with sugar
      sweetened beverage intake in youth.
AB  - OBJECTIVE: To examine associations between use of school vending machines and
      fast-food restaurants and youth intake of sugar-sweetened beverages. DESIGN: A
      cross-sectional observational study. SUBJECTS/SETTING: From a group randomized
      obesity intervention, we analyzed baseline data from 1,474 students in 10
      Massachusetts middle schools with vending machines that sold soda and/or other
      sweetened drinks. MAIN OUTCOME MEASURES: Daily sugar-sweetened beverage
      consumption (regular soda, fruit drinks, and iced tea), purchases from school
      vending machines, and visits to fast-food restaurants in the preceding 7 days
      were estimated by self-report. STATISTICAL ANALYSES PERFORMED: Chi(2) and
      nonparametric tests were performed on unadjusted data; multivariable models
      adjusted for sex, grade, body mass index, and race/ethnicity, and accounted for
      clustering within schools. RESULTS: Among 646 students who reported using school
      vending machines, 456 (71%) reported purchasing sugar-sweetened beverages.
      Overall, 977 students (66%) reported eating at a fast-food restaurant. Sugar
      sweetened beverage intakes averaged 1.2 servings per day. In adjusted models,
      relative to no vending machine purchases, servings per day increased by 0.21 for
      one to three purchases per week (P=0.0057), and 0.71 with four or more purchases
      (P<0.0001). Relative to no fast-food restaurant visits, sugar-sweetened beverage
      servings per day increased by 0.13 with one visit per week (P=0.07), 0.49 with
      two to three visits (P=0.0013), and by 1.64 with four or more visits (P=0.0016).
      CONCLUSIONS: Among students who use school vending machines, more report buying
      sugar-sweetened beverages than any other product category examined. Both school
      vending machine and fast-food restaurant use are associated with overall sugar
      sweetened beverage intake. Reduction in added dietary sugars may be attainable by
      reducing use of these sources or changing product availability.

PMID- 17000196
TI  - Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for
      effective dietary management.
AB  - Dietary fructose induces abdominal symptoms in patients with fructose
      malabsorption, but there are no published guidelines on its dietary management.
      The objective was to retrospectively evaluate a potentially successful diet
      therapy in patients with irritable bowel syndrome and fructose malabsorption.
      Tables detailing the content of fructose and fructans in foods were constructed.
      A dietary strategy comprising avoidance of foods containing substantial free
      fructose and short-chain fructans, limitation of the total dietary fructose load,
      encouragement of foods in which glucose was balanced with fructose, and co
      ingestion of free glucose to balance excess free fructose was devised. Sixty-two
      consecutively referred patients with irritable bowel syndrome and fructose
      malabsorption on breath hydrogen testing underwent dietary instruction. Dietary
      adherence and effect on abdominal symptoms were evaluated via telephone interview
      2 to 40 months (median 14 months) later. Response to the diet was defined as
      improvement of all symptoms by at least 5 points on a -10- to 10-point scale.
      Forty-eight patients (77%) adhered to the diet always or frequently. Forty-six
      (74%) of all patients responded positively in all abdominal symptoms. Positive
      response overall was significantly better in those adherent than nonadherent (85%
      vs 36%; P<0.01), as was improvement in individual symptoms (P<0.01 for all
      symptoms). This comprehensive fructose malabsorption dietary therapy achieves a
      high level of sustained adherence and good symptomatic response.

PMID- 17000197
TI  - Statistical methods for estimating usual intake of nutrients and foods: a review
      of the theory.
AB  - Although 24-hour recalls are frequently used in dietary assessment, intake on a
      single day is a poor estimator of long-term usual intake. Statistical modeling
      mitigates this limitation more effectively than averaging multiple 24-hour
      recalls per respondent. In this article, we describe the statistical theory that
      underlies the four major modeling methods developed to date, then review the
      strengths and limitations of each method. We focus on the problem of estimating
      the distribution of usual intake for a population from 24-hour recall data,
      giving special attention to the problems inherent in modeling usual intake for
      foods or food groups that a proportion of the population does not consume every
      day (ie, episodically consumed foods). All four statistical methods share a
      common framework. Differences between the methods arise from different
      assumptions about the measurement characteristics of 24-hour recalls and from the
      fact that more recently developed methods build upon their predecessor(s). These
      differences can result in estimated usual intake distributions that differ from
      one another. We also demonstrate the need for an improved method for estimating
      usual intake distributions for episodically consumed foods.

PMID- 17000198
TI  - Insurance coverage for obesity treatment.
AB  - Recent work demonstrates the benefits of weight loss from intensive lifestyle
      modification. One barrier to counseling may be lack of reimbursement. We sought
      to quantify the obesity coverage policies of insurers in Pennsylvania. A three
      page questionnaire was sent to eligible Pennsylvania health plans. Respondents
      included company medical directors and administrators from other departments,
      including public relations, provider relations, disease management, and
      utilization review. The questionnaire inquired about major treatment modalities
      for obesity, including details of coverage. Sixteen of 19 eligible plans (84%)
      responded. All plans provided some coverage for bariatric surgery. Nine out of 16
      companies (56%) stated that they covered individual dietary counseling, but only
      five paid for intensive counseling. Less than 50% of plans reimbursed other forms
      of lifestyle modification or weight loss medication. Surgery was covered
      significantly more often than all other treatment modalities (P<0.02 for all
      comparisons). No differences in reimbursement were found by plan type or by
      number of enrollees. Insurance reimbursement for obesity in Pennsylvania does not
      consistently reflect recent evidence for the benefits of lifestyle modification.
      Given the increasing evidence for the clinical and cost-effectiveness of
      nonsurgical weight loss therapy, coverage policies may begin to change.

PMID- 17000199
TI  - Body mass index, sex, interview protocol, and children's accuracy for reporting
      kilocalories observed eaten at school meals.
AB  - This pilot study investigated body mass index (BMI; calculated as kg/m(2)), sex,
      interview protocol, and children's accuracy for reporting kilocalories. Forty 4th
      grade children (20 low-BMI: >or=5th and <50th percentiles, 10 boys, 15 African
      American; 20 high-BMI: >or=85th percentile, 10 boys, 15 African American) were
      observed eating school meals (breakfast, lunch) and interviewed either that
      evening about the prior 24 hours or the next morning about the previous day, with
      10 low-BMI (5 boys) and 10 high-BMI (5 boys) children per interview protocol.
      Five kilocalorie variables were analyzed using separate four-factor (BMI group,
      sex, race, interview protocol) analyses of variance. No effects were found for
      reported or matched kilocalories. More kilocalories were observed (P<0.02) and
      omitted (P<0.05) by high-BMI than low-BMI children. For intruded kilocalories,
      means were smaller (better) for high-BMI girls than high-BMI boys, but larger for
      low-BMI girls than low-BMI boys (interaction P<0.04); low-BMI girls intruded the
      most while high-BMI girls intruded the least. For interview protocol, omitted and
      intruded kilocalories were higher (worse), although not significantly so (P
      values <0.11), for interviews about the previous day than the prior 24 hours.
      These results illuminate relations of BMI, sex, interview protocol, and
      children's reporting accuracy, and are consistent with results concerning BMI and
      sex from studies with adults.

PMID- 17000200
TI  - Visual plate waste in hospitalized patients: length of stay and diet order.
AB  - The purpose of this pilot research was to investigate the effect of diet order,
      sex, diagnosis, and length of stay on visual lunch plate waste in hospitalized
      patients. Information on 346 patients was collected using the computer program
      CBORD Diet Office. Visual plate waste during lunch was measured and analyzed for
      4 consecutive days. Neither sex nor diagnosis at admittance was associated with
      visual plate waste. However, the odds of visual plate waste increased by 14.1%
      for every day a patient was admitted. In patients receiving a diabetic diet
      order, odds of visual plate waste decreased by 61.2%, indicating there was
      reduction in plate waste. Conversely, in patients receiving altered consistency
      diet orders, odds of visual plate waste increased by 344%, signifying a rise in
      plate waste. Due to an increase of visual plate waste associated with long length
      of stay and altered consistency diet orders, registered dietitians working in
      acute-care facilities need to develop strategies to create cost-effective,
      nutritionally balanced, altered consistency diets that would enhance patient
      acceptance and consumption of food.

PMID- 17000201
TI  - Can self-reported dieting and dietary restraint identify underreporters of energy
      intake in dietary surveys?
AB  - Underreporting is endemic in most dietary studies and ways to reliably identify
      individuals who may underreport energy intake are needed. Whether questions on
      self-reported dieting and dietary restraint, in addition to weight status, would
      identify individuals who may underreport energy intakes was examined in a United
      Kingdom representative survey. Mean daily energy intake was calculated from the 7
      day dietary record of 668 men and 826 women. Reported physical activity was used
      to assign each subject's activity level and to calculate estimated energy
      requirements from published equations. Underreporting was calculated as estimated
      energy requirements minus energy intake with adjustment for daily variation. The
      Dutch Eating Behavior Questionnaire assessed dietary restraint. Underreporting
      was higher in men and women reporting current dieting than nondieters (P<0.001)
      and higher in high-restrained (P<0.001) than low-restrained. When stratified by
      body mass index category, in men these associations were only significant in the
      overweight (P<0.001). Dieting was associated with greater underreporting in both
      lean (P<0.01) and overweight women (P<0.001). Underreporting was higher in lean
      high-restrained women than low-restrained (P=0.02), but similar in overweight
      women regardless of restraint score. Questions to assess dietary restraint and
      current dieting may be useful tools to identify and evaluate underreporting at an
      individual level in dietary surveys.

PMID- 17000202
TI  - Sex differences in dieting trends, eating habits, and nutrition beliefs of a
      group of midwestern college students.
AB  - The influence of sex on dietary trends, eating habits, and nutrition self
      assessment and beliefs of a group of college students at a large Midwestern
      university was investigated. A questionnaire was completed by 105 male and 181
      female undergraduate students. Men had significantly higher (P<0.0001) height,
      weight, and body mass index values. Significantly higher percentages of women
      than men had tried a low-fat diet (P=0.0075) and a low-carbohydrate diet
      (P=0.0285). Significantly lower percentages of women than men had never tried a
      diet (P=0.0173). Significantly higher percentages of women than men reported
      gaining nutrition knowledge from family (P=0.0033) and magazines/newspapers
      (P=0.0345). Significantly higher percentages of women than men agreed that they
      had too much sugar in their diets (P=0.0157), that it is important to limit
      carbohydrate consumption (P=0.0077), that it is important to limit the amount of
      fat consumed to lose weight (P=0.0194), and that they needed to lose weight
      (P<0.0001). It is important to eat a variety of foods for good health according
      to 94.4% of subjects. Sex differences existed in these college students with
      regard to anthropometric measurements, certain choices of diets, some sources of
      nutrition knowledge, and some nutrition beliefs.

PMID- 17000203
TI  - Dietetics students possess negative attitudes toward obesity similar to
      nondietetics students.
AB  - This study explored attitudes toward obesity between dietetics and nondietetics
      majors at Ohio University and their relationship with dietary intake and body
      composition. A convenience sample comprised of 76 female dietetics (n=38) and
      nondietetics (n=38) majors was assessed for attitudes toward obesity using a
      validated Fat Phobia Scale. Dietary intake and percent body fat were measured
      using a food frequency questionnaire and air displacement plethysmography,
      respectively. Results show that both groups were well matched with respect to
      age, weight, and percent body fat. The two groups were similar with respect to
      negative attitudes toward obesity and these perceptions were comparable to norms
      reported in previous studies. However, there were intriguing, but subtle,
      differences in the rating of adjectives comprising the Fat Phobia Scale and in
      dietary intake between the groups. Together, these results suggest that dietetics
      students are no more or less susceptible to negative attitudes toward obesity
      than their peers.

PMID- 17000204
TI  - Electronic health record: where does nutrition fit in?

PMID- 17000205
TI  - Cutaneous vasculitis during selective serotonin reuptake inhibitor therapy.

PMID- 17000206
TI  - My personal philosophy for academic medicine.

PMID- 17000207
TI  - Metabolic syndrome and risk of cardiovascular disease: a meta-analysis.
AB  - PURPOSE: The use of different definitions of the metabolic syndrome has led to
      inconsistent results on the association between the metabolic syndrome and risk
      of cardiovascular disease. We examined the association between the metabolic
      syndrome and risk of cardiovascular disease. METHODS: A MEDLINE search (1966
      April 2005) was conducted to identify prospective studies that examined the
      association between the metabolic syndrome and risk of cardiovascular disease.
      Information on sample size, participant characteristics, metabolic syndrome
      definition, follow-up duration, and endpoint assessment was abstracted. RESULTS:
      Data from 21 studies met the inclusion criteria and were included. Individuals
      with the metabolic syndrome, compared to those without, had an increased
      mortality from all causes (relative risk [RR] 1.35; 95% confidence interval [CI],
      1.17-1.56) and cardiovascular disease (RR 1.74; 95% CI, 1.29-2.35); as well as an
      increased incidence of cardiovascular disease (RR 1.53; 95% CI, 1.26-1.87),
      coronary heart disease (RR 1.52; 95% CI, 1.37-1.69) and stroke (RR 1.76; 95% CI,
      1.37-2.25). The relative risk of cardiovascular disease associated with the
      metabolic syndrome was higher in women compared with men and higher in studies
      that used the World Health Organization definition compared with studies that
      used the Adult Treatment Panel III definition. CONCLUSION: This analysis strongly
      suggests that the metabolic syndrome is an important risk factor for
      cardiovascular disease incidence and mortality, as well as all-cause mortality.
      The detection, prevention, and treatment of the underlying risk factors of the
      metabolic syndrome should become an important approach for the reduction of the
      cardiovascular disease burden in the general population.

PMID- 17000208
TI  - Allergy immunotherapy for primary care physicians.
AB  - Allergic diseases affect a large proportion of the population of the United
      States. Although there are many effective pharmacologic therapies available, only
      allergen-specific immunotherapy has been shown to have significant and long
      lasting therapeutic and immunomodulatory effects for the management of allergic
      rhinitis, allergic asthma, and venom hypersensitivity. Allergen immunotherapy
      requires a build-up phase as the dose of the vaccine is increased until a
      therapeutic (maintenance) level is achieved. This maintenance dose is usually
      continued for 3 to 5 years. Most patients tolerate immunotherapy well, but local
      reactions are not uncommon. Immunotherapy should only be administered in a
      physician's office because some patients may experience systemic anaphylactic
      reactions requiring immediate therapy. Even with newer therapies on the horizon,
      allergen immunotherapy will continue to have an important role in the treatment
      of allergic diseases.

PMID- 17000209
TI  - An atypical complication of atypical pneumonia.

PMID- 17000210
TI  - Trouble below the surface.

PMID- 17000211
TI  - The tarnished tongue.

PMID- 17000212
TI  - Pain and a purple lesion.

PMID- 17000213
TI  - The heart remembers.

PMID- 17000214
TI  - COPD?

PMID- 17000215
TI  - Acute, severe noncardiac conditions in patients with acute myocardial infarction.
AB  - PURPOSE: The study's purpose was to determine the prevalence and prognostic
      importance of acute, severe, noncardiac conditions present at the time of an
      acute myocardial infarction (AMI). METHODS: We identified consecutive patients
      with AMI who were discharged from Yale-New Haven Hospital between January 1,
      1997, and June 30, 2000. Acute, noncardiac conditions that were present at
      admission were abstracted from patient records and graded by severity (imminent
      threat to life; other significant condition that would warrant admission). We
      examined the prognostic importance of these conditions on hospital mortality in
      multivariable logistic models. The study included 1145 patients with AMI, of whom
      8.5% (n=97) presented with an acute, life-threatening, noncardiac condition at
      admission and 19.5% (n=223) presented with another significant noncardiac
      condition. RESULTS: Hospital mortality was 25.8% and 9.0%, respectively, for
      patients who presented with life-threatening and other significant noncardiac
      conditions, compared with 4.6% for patients without either of these conditions.
      In multivariable analysis, life-threatening noncardiac conditions were associated
      with increased hospital mortality after adjusting for demographic factors,
      medical history, clinical presentation, cardiac severity, and initial therapy
      (odds ratio 2.5; 95% confidence interval [CI], 1.2-5.2). No increased hospital
      mortality risk was found for other significant noncardiac conditions in the risk
      adjusted analyses (odds ratio 1.0; 95% CI, 0.5-1.7). CONCLUSIONS: A subgroup of
      patients with AMI presented with a life-threatening noncardiac condition, which
      was associated with a marked increase in the risk of death during the
      hospitalization. Despite the excessive mortality risk associated with concomitant
      noncardiac conditions, this subset of patients with AMI are poorly described in
      current literature.

PMID- 17000216
TI  - Pulmonary embolism in patients with chronic obstructive pulmonary disease or
      congestive heart failure.
AB  - BACKGROUND: The diagnosis of pulmonary embolism (PE) is often unreliable in
      patients with chronic obstructive pulmonary disease (COPD) or congestive heart
      failure (CHF). SUBJECTS AND METHODS: Registro Informatizado de la Enfermedad
      TromboEmbolica (RIETE) is an ongoing registry of consecutive patients with acute
      venous thromboembolism. In this study, the clinical characteristics, laboratory
      findings, and clinical outcomes of all enrolled patients with acute PE, with or
      without underlying cardiopulmonary diseases, were compared and contrasted. In
      addition, the performance of 2 clinical models for the diagnosis of PE was
      retrospectively evaluated. RESULTS: As of January 2005, 4444 patients with
      symptomatic PE have been enrolled in RIETE. Of those, 632 patients (14%) had COPD
      and 422 (9.5%) had CHF. Significant differences were found in clinical
      presentation and 3-month outcomes among the 3 groups. With the Geneva model,
      there was a lower percentage of PE patients with COPD (relative risk [RR] 0.82;
      95% confidence interval [CI], 0.66-1.02) or CHF (RR 0.73; 95% CI, 0.56-0.95) who
      fell into the low pretest probability category, compared with patients with
      neither. Besides, the percentage of patients with high probability of PE was
      similar among the 3 patient groups. The frequency of COPD (61%) and CHF (72%)
      patients with a high pretest probability for PE increased when using the Pisa
      score, but the percentage of COPD patients into the high probability group was
      lower (RR 0.60; 95% CI, 0.51-0.71). CONCLUSIONS: Significant differences exist in
      PE patients with and without underlying cardiopulmonary diseases. The performance
      of the 2 clinical prediction models varied according to the presence or absence
      of underlying COPD or CHF.

PMID- 17000217
TI  - Antibiotic therapy and 48-hour mortality for patients with pneumonia.
AB  - PURPOSE: Although numerous articles have demonstrated that recommended empiric
      antimicrobial regimens are associated with decreased mortality at 30 days, there
      is controversy over whether appropriate antibiotic selection has a beneficial
      impact on mortality within the first 48 to 96 hours after admission. Our aim was
      to determine whether the use of guideline-concordant antibiotic therapy is
      associated with decreased mortality within the first 48 hours after admission for
      patients with pneumonia. METHODS: A retrospective cohort study was conducted at
      two tertiary teaching hospitals in San Antonio, Texas. A propensity score was
      used to balance the covariates associated with the use of guideline-concordant
      antimicrobial therapy. A multivariable logistic regression model was used to
      assess the association between mortality within 48 hours and the use of guideline
      concordant antibiotic therapy, after adjusting for potential confounders
      including the propensity score. RESULTS: Information was obtained on 787 patients
      with community-acquired pneumonia. The median age was 60 years, 79% were male,
      and 20% were initially admitted to the intensive care unit. At presentation 52%
      of subjects were low risk, 34% were moderate risk, and 14% were high risk. Within
      the first 48 hours, 20 patients died. After adjustment for potential confounders,
      the use of guideline-concordant antimicrobial therapy (odds ratio 0.37, 95%
      confidence interval, 0.14-0.95) was significantly associated with decreased
      mortality at 48 hours after admission. CONCLUSION: Using initial empiric
      guideline-concordant antimicrobial therapy is associated with decreased mortality
      at 48 hours. Further research needs to investigate methods to ensure that
      patients with community-acquired pneumonia are treated with appropriate
      antimicrobial therapies.

PMID- 17000218
TI  - Impact of guideline-concordant empiric antibiotic therapy in community-acquired
      pneumonia.
AB  - PURPOSE: We evaluated the impact of guideline-concordant empiric antibiotic
      therapy on time to clinical stability, time to switch therapy, length of hospital
      stay, and mortality among patients with community-acquired pneumonia. METHODS:
      This is a retrospective cohort study of all adult community-acquired pneumonia
      patients managed at 5 community hospitals from November 1, 1999 to April 30,
      2000. Patients were stratified into guideline-concordant and discordant groups as
      defined by the 2001 American Thoracic Society and the 2003 Infectious Diseases
      Society of America guidelines. Time to clinical stability, time to switch
      therapy, length of hospital stay, and in-hospital mortality were evaluated in per
      protocol and intention-to-treat stepwise regression models that included the
      outcome as the dependent variable, guideline-concordant antibiotic therapy as the
      independent variable, and Pneumonia Severity Index score as a covariate. RESULTS:
      Of the 631 evaluable patients, 357 (57%) received guideline-concordant empiric
      antibiotic therapy. Groups were similar with respect to age, sex, comorbidities,
      severity of illness, and processes of care. Guideline-concordant antibiotic
      therapy was associated with a significant decrease in time to switch therapy (P <
      or =.01), length of hospital stay (P < or =.01), and in-hospital mortality
      (P=.04) for both per-protocol and intention-to-treat analyses. In addition,
      guideline-concordant antibiotic therapy was associated with a significant
      decrease in time to clinical stability for intention-to-treat analysis only
      (P=.03). CONCLUSIONS: Among hospitalized community-acquired patients, guideline
      concordant antibiotic therapy is associated with improved in-hospital survival
      and shorter time to clinical stability, time to switch therapy, and length of
      hospital stay.

PMID- 17000219
TI  - Pneumonia during pregnancy.
AB  - BACKGROUND: We determined the incidence, clinical course, risk factors, and
      outcomes of community-acquired pneumonia complicating pregnancy. METHODS: A
      prospective study was performed of pregnant and nonpregnant patients in the same
      age range who presented to any of 6 hospitals in Edmonton, Alberta, with signs
      and symptoms of pneumonia together with an acute infiltrate evident on chest
      radiography compatible with pneumonia. RESULTS: There were 28 patients with
      pneumonia during pregnancy, for an incidence of 1.1 per 1000 deliveries, whereas
      there were 333 nonpregnant females in the 20- to 40-year age group with
      pneumonia, for an incidence of 1.3 per 1000. No significant differences in signs
      and symptoms were present between the two groups. Asthma requiring treatment was
      present in 46.4% of the pregnant patients, compared with 17.1% of the nonpregnant
      patients. No maternal or fetal deaths were noted except an abortion at 10 weeks
      of gestation. No anomaly was detected among newborns. Two patients had preterm
      deliveries. CONCLUSIONS: Pneumonia is well tolerated during pregnancy. Asthma may
      be a predisposing factor for pneumonia in this group of patients.

PMID- 17000220
TI  - Thoracic empyema in patients with community-acquired pneumonia.
AB  - PURPOSE: The objective of this study was to update the incidence and natural
      history of empyema in patients admitted to hospital with community-acquired
      pneumonia (CAP). METHODS: A prospective population-based study of 3675 patients
      with a diagnosis of CAP was carried out. Patients were classified as "definite
      empyema" based on one or more of the following criteria: presence of
      microorganisms in pleural fluid Gram stain or culture, pleural pH less than 7.2
      associated with radiographic features of empyema, or frank pus in the pleural
      space at the time of thoroscopy. All others were classified as either "suspected
      empyema" or CAP. We then compared characteristics and outcomes between subgroups.
      RESULTS: A diagnosis of empyema was made in 47 patients (1.3%) by the attending
      physician; 24 patients (0.7%) met criteria for definite cases. Few clinical,
      laboratory, or radiographic features were useful in differentiating patients with
      definite empyema. The most commonly isolated pathogen from pleural fluid of
      patients with definite empyema was Streptococcus milleri group (50%). The in
      hospital mortality rate for patients with definite empyema was 4.2%. CONCLUSION:
      In the 21st century, empyema is an uncommon complication of CAP with an incidence
      of 0.7%. The S. milleri group has emerged as the most common causative microbial
      pathogen. The diagnosis remains difficult, although outcomes have improved from
      that previously reported.

PMID- 17000221
TI  - Risk factors for work disability in severe adult asthma.
AB  - PURPOSE: We aimed to elucidate the prevalence of and risk factors for work
      disability in severe adult asthma and to evaluate the impact of work disability
      on downstream health outcomes. METHODS: We used data from a prospective cohort
      study of 465 adults with severe asthma. Structured telephone interviews
      ascertained asthma status and employment history. A job exposure matrix (JEM) was
      used to characterize the likelihood of workplace exposure to "asthmagens."
      RESULTS: The prevalence of asthma-related complete work disability was 14% among
      working-age adults with severe asthma (95% confidence interval, 11%-18%). Among
      those who were currently employed, the prevalence of partial work disability was
      38% (95% confidence interval, 31%-45%). Sociodemographic (P = .027) and medical
      factors (P = .020) were related to the risk of complete work disability. Both
      sociodemographic characteristics (P = .06) and work exposures based on the JEM (P
      = .012) were related to partial work disability. In additional models, poorer
      asthma severity, physical health status, and mental health status were all
      associated with a higher risk of complete and partial work disability.
      CONCLUSIONS: Work disability is common among adults with severe asthma. There are
      three sets of risk factors for work disability that are potentially modifiable:
      smoking, workplace exposures, and asthma severity.

PMID- 17000222
TI  - Withdrawing implantable defibrillator shock therapy in terminally ill patients.
AB  - PURPOSE: The purpose of this study is to review a multidisciplinary strategy used
      to identify patients with terminal illnesses and initiate withdrawal of
      implantable cardioverter defibrillator (ICD) shock therapy as part of a
      comprehensive comfort care approach. With indications for ICDs increasing, more
      patients are receiving devices. Once protected from an arrhythmic death, these
      patients may develop other terminal diseases such as cancer or congestive heart
      failure. It is appropriate to withdraw defibrillator shock therapy when such
      patients desire only comfort care. METHODS: The charts of ICD patients who had
      died were reviewed. Two groups emerged: Group 1 (20) included patients whose
      defibrillator was turned off through the comprehensive comfort care approach.
      Group 2 (43) included patients whose clinical course was so rapid that the
      defibrillator was not turned off. Pacing therapy was not withdrawn in either
      group. RESULTS: Defibrillator discharges, cause of death, and time from ICD
      discharge to death were compared. Group 2 patients died more acutely than Group
      1. Group 1 experienced fewer shocks prior to death when compared to Group 2.
      Comparing pacemaker dependent and non-dependent patients, there was no difference
      in the time between therapy discontinuation and death. CONCLUSION: This is the
      largest study to date to review the characteristics of patients with ICDs and
      terminal illness. Only one-third of terminally ill patients with ICDs were able
      to have shock therapy withdrawn as part of a comfort care strategy. These
      patients experienced fewer shocks in the final days of their illness.

PMID- 17000223
TI  - TLR9-based immunotherapy for allergic disease.
AB  - A significant amount of data generated over the last few years supports the
      contention that Toll-like receptor (TLR) 9-based immunotherapy is effective in
      the prevention and treatment of animal models of allergic disorders. We will
      review here our experience with two distinct therapeutic strategies: TLR9-based
      immunomodulation and TLR9-based vaccination. Immunomodulation of allergic
      inflammation by TLR9 ligand (TLR9-L) is transient. It prevents both the early and
      late phases of the allergic reaction in experimental models of allergic asthma,
      rhinitis, and conjunctivitis. It also reverses ongoing allergic inflammation.
      Indoleamine 2.3-dioxygenase, the rate-limiting enzyme of tryptophan, is induced
      by TLR9-L and mediates, in part, these anti-inflammatory effects. TLR9-based
      immunomodulation is independent of allergens and, therefore, has a potential
      therapeutic advantage in a broad spectrum of allergic patients. On the other
      hand, TLR9-based vaccination therapy is an allergen-specific mode of
      immunotherapy, which provides long-term inhibition of allergen-specific
      hypersensitivities. Current clinical trials with TLR9-based immunotherapy
      demonstrate high immunogenic and therapeutic efficacy, as well as improved safety
      when compared with conventional allergen desensitization. Thus, if proven
      efficient, therapeutic strategies with TLR9-L may revolutionize the current
      treatment of allergic diseases.

PMID- 17000224
TI  - Predictors of long-term mortality in patients with ventilator-associated
      pneumonia.
AB  - PURPOSE: To determine the long-term outcome of ventilator-associated pneumonia
      (VAP) and identify factors associated with increased mortality. METHODS: We
      retrospectively studied 671 patients with VAP admitted to an intensive care unit
      between 1994 and 2000. We determined long-term and out-of-hospital mortality for
      these patients. RESULTS: The in-hospital mortality was 42.3%; 19.8% of patients
      had concomitant bacteremia, the mortality was 59.7% versus 38.0% for those
      without bacteremia (P <.001). The factors associated with increased hospital
      mortality by univariable analysis were: diagnosis on admission, the need of
      vasopressors during the stay in the intensive care unit, not undergoing a
      tracheostomy, the absence of fever, the presence of concomitant bacteremia, and
      renal failure or the need for dialysis. Patients transferred from an outside
      hospital and patients with normal serum bicarbonate, serum total bilirubin <2
      mg/dL, and platelets >120x4> 10(3)/microL had a lower in-hospital mortality. All
      of these factors except bilirubin level, platelet count, transfer from outside
      hospital, and serum bicarbonate remained significant on multivariable analysis.
      The estimated mortality at 1, 3 and 5 years is 25.9% (95% confidence interval
      [CI], 20.2-30.1%), 33.6% (95% CI, 27.4-39.2%) and 44.7% (95% CI, 38.1-50.6%),
      respectively. CONCLUSIONS: VAP is associated with a high rate of hospital and
      long-term mortality. The presence of bacteremia is associated with a high
      mortality. The 5-year estimated mortality of the survivors is less than 50%.

PMID- 17000225
TI  - Deep venous thrombosis and pulmonary embolism in hospitalized patients with
      sickle cell disease.
AB  - BACKGROUND: As would be expected with a hypercoagulable state, pulmonary embolism
      (PE) occurs in sickle cell disease (SCD). Its frequency, however, is
      undetermined, largely because of difficulties in distinguishing it from
      thrombosis in situ. The prevalence of deep venous thrombosis (DVT) is also
      undetermined in patients with SCD. Knowing the prevalence of DVT would be an
      important step in the overall assessment of the risk of PE in these patients.
      METHODS: Data from the National Hospital Discharge Survey were assessed. RESULTS:
      In patients <age 40 years, 7000 of 1,581,000 (0.44%) with SCD had a discharge
      diagnosis of PE compared with 59,000 of 48,611,000 (0.12%) of African Americans
      without SCD. The prevalence of DVT was similar in patients < age 40 with SCD,
      7000 of 1,581,000 (0.44%) and in African Americans who did not have SCD, 193,000
      of 48,611,000 (0.40%). CONCLUSION: The high prevalence of apparent PE in patients
      with SCD, compared with non-SCD African-American patients of the same age and the
      comparable prevalence of DVT in both groups are compatible with the concept that
      thrombosis in situ might be present in many. On the other hand, the data suggest
      that PE is not rare in patients with SCD. This suggests that PE might be an
      etiologic factor in patients with SCD who develop respiratory symptoms. In such
      patients, an imaging procedure might be appropriate.

PMID- 17000226
TI  - Melatonin reduces night blood pressure in patients with nocturnal hypertension.
AB  - PURPOSE: Nocturnal hypertension is associated with a high risk of morbidity and
      mortality. A blunted nocturnal surge in melatonin excretion has been described in
      nondipping hypertensive patients. We therefore studied the potency of melatonin
      to reduce nighttime blood pressure (BP) in treated hypertensive patients with
      nocturnal hypertension. PATIENTS AND METHODS: Thirty-eight treated hypertensive
      patients (22 males, mean age 64+/-11 years) with confirmed nocturnal hypertension
      (mean nighttime systolic BP >125 mm Hg), according to repeated 24-hour ambulatory
      blood pressure monitoring (ABPM), were randomized in a double-blind fashion to
      receive either controlled release (CR)-melatonin 2 mg or placebo 2 hours before
      bedtime for 4 weeks. A 24-hour ABPM was then performed. RESULTS: Melatonin
      treatment reduced nocturnal systolic BP significantly from 136+/-9 to 130+/-10 mm
      Hg (P=.011), and diastolic BP from 72+/-11 to 69+/-9 mm Hg (P=.002), whereas
      placebo had no effect on nocturnal BP. The reduction in nocturnal systolic BP was
      significantly greater with melatonin than with placebo (P=.01), and was most
      prominent between 2:00 AM and 5:00 AM (P=.002). CONCLUSIONS: Evening CR-melatonin
      2 mg treatment for 4 weeks significantly reduced nocturnal systolic BP in
      patients with nocturnal hypertension. Thus, an addition of melatonin 2 mg at
      night to stable antihypertensive treatment may improve nocturnal BP control in
      treated patients with nocturnal hypertension.

PMID- 17000227
TI  - Overview of current learning theories for medical educators.

PMID- 17000228
TI  - Ovarian cyst torsion and extreme ovarian stimulation in a premenopausal patient
      treated with tamoxifen for ductal carcinoma in situ of the breast.
AB  - Tamoxifen is increasingly used in adjuvant endocrine therapy for postsurgery
      breast cancer patients and in chemoprevention for high-risk patients. We present
      a case of bilateral ovarian cyst development with consecutive unilateral cyst
      torsion and elevated serum estradiol in a premenopausal patient treated with
      tamoxifen after breast-conserving surgery.

PMID- 17000230
TI  - Announcement of inappropriate acts in the publication process.

PMID- 17000231
TI  - Quality improvement in gynecologic surgery: the new frontier.
AB  - The continual and disproportionate increase in health care costs without showing
      improvement has regulatory organizations and purchasers of surgical care
      demanding comparative documentation of surgical quality and outcomes. Support for
      implementing performance standards is derived from 2 risk-adjusted national
      surgical quality improvement programs which documented substantial decreases in
      perioperative morbidity and mortality. These dramatic improvements in patient
      outcomes and corresponding decreases in health care costs are transitioning to
      "pay-for-performance" for surgical disciplines. With the requisite budget-neutral
      environment, quality incentive payments will be offset by reduced reimbursement
      for substandard performances. For specialties that have not developed specific
      performance metrics, the implications are substantial. Therefore, the gynecologic
      surgical community has an exigent need to develop standards and methods to assess
      quality within our discipline that are specialty specific, equitable and risk
      adjusted.

PMID- 17000232
TI  - Four-dimensional ultrasonography of a true knot of the umbilical cord.
AB  - We describe the prenatal diagnosis of a true knot of the umbilical cord using the
      "hanging noose" sign. Changes in the tension of the knot, which are related to
      fetal movements, were studied with 4-dimensional ultrasonography.

PMID- 17000233
TI  - The use of progestational agents for preterm birth: lessons from a mouse model.
AB  - OBJECTIVE: On the basis of the recent Maternal Fetal Medicine Unit Networks
      clinical trial, the American College of Obstetricians and Gynecologists supports
      the administration of 17-alpha hydroxyprogesterone caproate to high-risk
      patients. Because inflammation/infection is believed to be a contributing factor
      in many cases of preterm birth, it is imperative to understand the effect of 17
      alpha hydroxyprogesterone caproate treatment in this clinical situation. STUDY
      DESIGN: Using a mouse model of localized intrauterine inflammation, we
      investigated the ability of progestational agents to prevent preterm birth. On
      gestational day 15 (E15), dams were assigned randomly to treatment with 17-alpha
      hydroxyprogesterone caproate, medroxyprogesterone acetate, or vehicle before
      intrauterine infusion of lipopolysaccharide. All dams were monitored for
      morbidity and preterm birth. Three separate sets of experiments were performed to
      assess different outcomes at 6, 24, and 96 hours. At 6 and 24 hours, C-reactive
      protein, interleukin-6, and interleukin-10 levels were measured in maternal serum
      by enzyme-linked immunosorbent assay. RESULTS: Pretreatment with 17-alpha
      hydroxyprogesterone caproate or medroxyprogesterone acetate before intrauterine
      lipopolysaccharide treatment significantly decreased the preterm birth rate,
      compared with lipopolysaccharide treatment alone. Medroxyprogesterone acetate
      treatment was more effective than 17-alpha hydroxyprogesterone caproate treatment
      in the prevention of preterm birth and resulted in live pups at term. Treatment
      with 17-alpha hydroxyprogesterone caproate was associated with significant
      maternal morbidity. CONCLUSION: In the setting of intrauterine inflammation,
      progestational agents decrease the preterm birth rate but can result in maternal
      morbidity. 17-Alpha hydroxyprogesterone caproate should not be used in patients
      who are suspected of having subclinical infection and/or acute preterm labor. The
      mechanisms by which progestational agents inhibit preterm birth warrants further
      investigations so that the use of this drug to appropriate populations could be
      pursued without undue fetal or maternal harm.

PMID- 17000234
TI  - Progesterone reduces lipopolysaccharide induced interleukin-6 secretion in
      fetoplacental chorionic arteries, fractionated cord blood, and maternal
      mononuclear cells.
AB  - OBJECTIVE: The purpose of this study was to characterize effect of progesterone
      (P4) on interleukin-6 (IL-6) production by fetoplacental artery explants, fetal
      granulocytes, and fetal and maternal mononuclear cells. STUDY DESIGN: Arteries
      and cord blood were obtained from 5 term pregnancies undergoing repeat cesarean
      section. Maternal blood was obtained from another 6 women at 16 to 20 weeks'
      gestation. Tissues were fractionated by dissection or Histopaque gradient.
      Specimens were incubated in physiologic media then exposed to lipopolysaccharide
      (LPS) or P4 alone, or pretreated with P4 and then exposed to LPS. Samples were
      evaluated for IL-6 by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Arteries and fetal and maternal mononuclear cells exposed to LPS increased IL-6
      secretion by 9-, 27-, and 29-fold, respectively. P4 pretreatment blocked LPS
      induction of IL-6. Fetal granulocytes did not increase IL-6 production in
      response to LPS exposure. CONCLUSION: LPS induces IL-6 in arteries and fetal and
      maternal mononuclear cells. P4 pretreatment significantly blocks this effect in
      these cell populations, suggesting possible targets for anti-inflammatory actions
      of P4 in prevention of preterm birth.

PMID- 17000235
TI  - The Alabama preterm birth study: corticosteroids and neonatal outcomes in 23- to
      32-week newborns with various markers of intrauterine infection.
AB  - OBJECTIVE: Intrauterine inflammation/infection is cited as a contraindication to
      the use of corticosteroids (CS). Our goal was to determine if CS given prenatally
      to enhance fetal maturity were harmful to infants with various indications of
      intrauterine infection. STUDY DESIGN: This was a retrospective analysis of data
      obtained from 457 consecutively enrolled infants delivered between 23 and 32
      weeks. Cultures and a histologic examination of the placenta, and cord blood
      interleukin (IL)-6 levels were obtained. Neonatal outcomes included
      periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH),
      respiratory distress syndrome (RDS), chronic lung disease (CLD), necrotizing
      enterocolitis (NEC), systemic inflammatory response syndrome (SIRS), and infant
      death. RESULTS: Of the 457 pregnancies, 57.6% had a positive placental culture,
      49.8% had histologic chorioamnionitis/funisitis, 28.8% had elevated cord IL-6
      levels, and 12.5% had clinical chorioamnionitis. With intrauterine
      infection/inflammation, none of the neonatal outcomes were significantly worse if
      mothers were treated with CS. For those with histologic
      chorioamnionitis/funisitis, of the outcomes historically improved with CS, RDS
      (59.9 vs 72.2% P = .16), IVH (9.7 vs 14.7% P = .38), and neonatal death (9.9 vs
      11.1% P = .82) all occurred less frequently with CS treatment, but differences
      were not significant. Similar results were seen for women with a positive
      placental culture. For women with an elevated IL-6, RDS was significantly reduced
      (59.4 vs 84.2 %, P = .045). Neonatal SIRS was significantly reduced with CS in
      women with histologic chorioamnionitis/funisitis (39.7 vs 65.7%, P = .005),
      positive placental cultures (32.7 vs 56.3%, P = .01), and elevated IL-6 levels
      (42.7 vs 73.7%, P = .02). CONCLUSION: In women with intrauterine
      infection/inflammation, CS use was not associated with significant worsening in
      any neonatal outcome, and was associated with significant reductions in RDS and
      SIRS. These data suggest that CS use may not be contraindicated in the presence
      of intrauterine inflammation/infection.

PMID- 17000236
TI  - A rapid MMP-8 bedside test for the detection of intra-amniotic inflammation
      identifies patients at risk for imminent preterm delivery.
AB  - OBJECTIVE: Matrix metalloproteinase-8 (MMP-8) is an enzyme that is released
      during neutrophil activation. MMP-8 amniotic fluid concentrations are elevated
      not only in patients with intra-amniotic infection, but also in patients with
      negative amniotic fluid cultures who deliver preterm neonates. The objective of
      this study was to determine whether the results of a rapid MMP-8 bedside test
      predict imminent preterm delivery. This test can be performed in 15 minutes and
      without laboratory equipment. STUDY DESIGN: Amniotic fluid was retrieved from 331
      patients admitted with increased preterm uterine contractions and intact
      membranes who met the inclusion criteria. Amniotic fluid was processed for
      microbial cultures, Gram stain, glucose concentration, and white blood cell
      count. Amniotic fluid samples were stored, and the MMP-8 rapid test was performed
      after delivery. End points included spontaneous preterm delivery within 48 hours,
      7 days, and 14 days. Diagnostic indices, predictive values, and likelihood ratios
      were calculated. RESULTS: The prevalence of spontaneous preterm delivery within
      48 hours, 7 days, and 14 days was 11.6% (38/327), 20.2% (66/327), and 24.5%
      (80/327), respectively (4 patients with augmentation of labor were excluded). A
      positive MMP-8 rapid test had a positive predictive value of 70% (23/33) for the
      identification of patients who delivered spontaneously within 48 hours, and 94%
      (31/33) for patients who were delivered within 7 days and 14 days (likelihood
      ratios: 17.5 [95% CI, 9-33.9], 61.3 [95% CI, 15.1-250], and 50 [95% CI, 12-196],
      respectively). CONCLUSION: The MMP-8 rapid test can identify patients at risk for
      preterm delivery within 7 days and 14 days. Moreover, a positive MMP-8 rapid test
      result can identify patients with intra-amniotic infection/inflammation with a
      high sensitivity and specificity. This rapid test will give clinicians a fast and
      accurate assessment of the inflammatory status of the amniotic cavity and allow
      for better identification of patients at risk for impending preterm delivery.

PMID- 17000237
TI  - Postnatal inflammatory rat model for cerebral palsy: too different from humans.
AB  - OBJECTIVE: In humans, cerebral palsy (CP) may originate from inflammation during
      the second and third trimesters of gestation when preoligodendrocytes (Pre-OL)
      are most vulnerable to an inflammatory insult. We studied a postnatal CP model to
      evaluate injury that would correlate with presence of Pre-OL in human pregnancy.
      STUDY DESIGN: On postnatal (P) days 2, 3, 4, 5 and 6, pups were treated with
      (lipopolysaccharide [LPS]) (n = 7; 30, 30, 60, 60, 120 microg/Kg) or saline (n =
      7). Neonates were tested for motor and cognitive development. Adult offspring
      performed beam walking and rotarod for motor activity. White matter damage was
      assessed with immunohistochemical Pre-OL markers (CNP, PLP). Statistical analysis
      included Mann-Whitney U and analysis of variance. RESULTS: LPS-treated animals
      performed negative geotaxis (P = .009) and surface righting (P = .01) earlier
      than controls. No differences were observed for other neonatal tests. Adult LPS
      treated offspring performed better in tests of motor control: rotarod (P = .01)
      and beam walking (P = .02). Pre-OL markers were altered in LPS-treated animals at
      both P22 (CNP and PLP increased in LPS, P < .01 and P < .001, respectively) and
      12 weeks (CNP and PLP decreased in LPS, P < .0001 and P < .03, respectively).
      CONCLUSION: Neonatal exposure to LPS induced white matter damage in the brain,
      accelerated neurodevelopment and motor tasks in adulthood. These are similar to
      findings from a postnatal hypoxic model suggesting that in the rodent, targeting
      the Pre-OL does not result in a CP phenotype.

PMID- 17000238
TI  - Maternal N-acetylcysteine suppresses fetal inflammatory cytokine responses to
      maternal lipopolysaccharide.
AB  - OBJECTIVE: Evidence suggests that maternal infections may induce fetal
      inflammatory responses. Because cytokine actions may be mediated by oxidative
      stress, we determined whether N-acetylcysteine, an antioxidant, can blunt fetal
      inflammatory responses to maternal lipopolysaccharide. STUDY DESIGN: Sprague
      Dawley near-term rats (n = 16) received intraperitoneal lipopolysaccharide (100
      microg/kg) at 30 minutes and saline solution or N-acetylcysteine (300 mg/kg) at
      150 minutes. An additional group received N-acetylcysteine before and after
      lipopolysaccharide administration. At 6 hours, rats were killed, and fetal and
      maternal blood cytokines were determined. RESULTS: After maternal
      lipopolysaccharide administration, fetal blood interleukin-6 markedly increased
      (3 +/- 2 to 1265 +/- 574 pg/mL); N-acetylcysteine that was given before or before
      and after lipopolysaccharide administration reduced fetal interleukin-6 response
      to control levels. A similar trend was observed for interleukin-1beta. No effect
      of N-acetylcysteine on fetal interleukin-10 levels was observed. CONCLUSION:
      Maternal N-acetylcysteine inhibits fetal cytokine responses to maternal
      lipopolysaccharide, even when given 2 hours after lipopolysaccharide injection.
      These results suggest that N-acetylcysteine may protect the fetus from sequelae
      of maternal inflammation.

PMID- 17000239
TI  - Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated
      preterm birth: an alternate tocolytic approach.
AB  - OBJECTIVE: We examined the hypotheses that vaginal indomethacin is more effective
      for prolonging gestation, and mediates its tocolytic actions via changes in
      cervical matrix metalloproteinase (MMP) activity, compared to oral. STUDY DESIGN:
      Pregnant rabbits induced with mifepristone received oral or vaginal indomethacin;
      or oral or vaginal vehicle once daily for 2 days. Premature delivery, fetal
      ductus arteriosus, and cervical MMP activity were assessed. RESULTS: Vaginal
      indomethacin delayed delivery >72 hours in 100% of the rabbits, extending
      gestation to 28.2 +/- 0.5 (P < .01) versus 26.4 +/- 0.3, 25.8 +/- 0.5, and 26.5
      +/- 0.3 days, for vaginal placebo, oral indomethacin, and oral vehicle,
      respectively. Fetal ductus arteriosus was patent in all groups. Vaginal
      indomethacin decreased MMP-1, -8, and -9 activities and increased TIMP-1 levels
      in the cervix. CONCLUSION: Vaginal indomethacin is more effective than oral for
      prolonging gestation in the rabbit. Its tocolytic effects may be mediated, in
      part, by alterations in cervical MMP activity.

PMID- 17000240
TI  - Characterization of differential gene expression profiles in diabetic embryopathy
      using DNA microarray analysis.
AB  - OBJECTIVE: The molecular mechanisms by which maternal diabetes impairs
      embryogenesis are not established. This study aimed to determine the
      developmental genes and molecular pathways that are involved in diabetic
      embryopathy, by comparing gene expression profiles in the yolk sacs between the
      embryos of diabetic and control rats by using DNA microarray analysis. STUDY
      DESIGN: Diabetes was induced in female rats by injecting streptozotocin (65
      mg/kg) intravenously. Glucose levels were controlled by subcutaneously implanting
      insulin pellets. The female rats were mated with normal male rats. At gestation
      day 4, the insulin pellets were removed from a group of animals, making them
      hyperglycemic. The animals with insulin pellets served as controls. At
      gestational day 12, embryos were explanted, and yolk sacs were collected. Total
      RNA, free of DNA contamination, was extracted from the yolk sacs. Complementary
      DNA probes were synthesized, labeled with Cy3 and Cy5 fluorescent dyes, and used
      to hybridize rat oligo-array containing 10,000 genes. Data were analyzed by using
      1-sample t test on log2 ratios, with P < .05 representing a significant
      difference. The changes in expression levels of important genes were verified
      with the use of a real-time polymerase chain reaction (PCR). RESULTS: Five
      microarray experiments produced consistent results. A total of 101 genes were
      found to be differentially expressed between the embryos of diabetic and control
      rats. Analyses that used PathwayAssist (Ariadne Genomics, Rockville, MD) revealed
      a number of potential signaling pathways and genes involved in insulin signaling
      and stress response (insulin 2, insulin-binding protein 1, GST pi1), cell growth
      (GAP43, CSF1R, HGF), calcium signaling (calbindin 3, CBP A6), and PKC signaling
      (PKCBP beta15, FABP5), in concert with prior biochemical and molecular findings.
      CONCLUSION: These observations show significant alterations in expression of
      developmental and stress response genes in diabetic embryopathy, and demonstrate,
      for the first time, that the yolk sac cells express insulin during early
      development. In addition, these data also demonstrate that hyperglycemia induces
      altered gene expression, resulting in aberrant cell signaling, morphogenesis, and
      embryopathy.

PMID- 17000241
TI  - Glyburide for the management of gestational diabetes: risk factors predictive of
      failure and associated pregnancy outcomes.
AB  - OBJECTIVE: The purpose of this study was to identify characteristics that may
      predict failure of glyburide therapy for the management of A2 gestational
      diabetes, and to evaluate whether those that fail are at increased risk for
      adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort of
      gestational diabetics requiring medical therapy (A2DM) treated between January
      2002 and July 2005. RESULTS: Of the 235 gestational diabetics identified, 79% of
      the 101 A2DMs were successfully treated with glyburide as first-line therapy.
      Those that failed had a higher mean glucose value on glucose challenge test (GCT)
      (200.5 +/- 57.3 vs 176.6 +/- 33.8 mg/dL, P = .019) and were more likely to have a
      GCT > or = 200 mg/dL (45 vs 22%, P = .043). Only GCT and GCT > or = 200 mg/dL
      were predictive of failure. Those successfully managed with glyburide had
      increased NICU admissions, primarily for hypoglycemia and respiratory distress,
      which resolved prior to discharge. There was no difference in birth weight,
      cesarean delivery, macrosomia, or shoulder dystocia. CONCLUSION: Predicting
      glyburide failure is difficult, but failure does not appear to be associated with
      increased adverse pregnancy outcomes.

PMID- 17000242
TI  - Bone density changes in women who receive thromboprophylaxis in pregnancy.
AB  - OBJECTIVE: The purpose of this study was to compare unfractionated heparin
      therapy to the low molecular weight heparin, enoxaparin sodium, and their effects
      on bone mineral density over the course of pregnancy. STUDY DESIGN: Pregnant
      patients whose condition required thromboprophylaxis were recruited in this
      prospective randomized controlled trial and were assigned to receive either
      unfractionated heparin therapy or low molecular weight heparin therapy. Bone
      mineral density was measured by dual energy x-ray absorptiometry at the proximal
      femur on enrollment and again shortly after delivery. RESULTS: One hundred twenty
      women were enrolled, and 98 women completed the study. There was no difference in
      the change in bone mineral density at the femoral neck (P = .054) or total
      proximal femur (P = .584) between groups. Only 1 of 40 patients (2.5%) who
      received unfractionated heparin therapy and 1 of 49 patients (2.0%) who received
      low molecular weight heparin therapy (P = 1.0) experienced bone loss of > or =
      10% at the femoral neck. CONCLUSION: In this study, the incidence of clinically
      significant bone loss (> or = 10%) in the femur in women who received
      thromboprophylaxis in pregnancy is approximately 2% to 2.5% and appears to be
      similar, regardless of whether the patient receives low molecular weight heparin
      therapy or unfractionated heparin therapy.

PMID- 17000243
TI  - Prevalence of factor V Leiden, prothrombin and methylene tetrahydrofolate
      reductase mutations in women with adverse pregnancy outcomes in Lebanon.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of factor V
      Leiden, prothrombin, and methylene tetrahydrofolate reductase gene mutations in
      women with adverse pregnancy outcome compared with women who had uneventful
      pregnancies. STUDY DESIGN: Between 2003 and 2005, pregnant women with > or = 1
      unexplained second trimester abortion, > or = 1 intrauterine fetal death, severe
      preeclampsia, or severe intrauterine growth restriction (study subjects) were
      compared with control subjects (uneventful pregnancy) for the frequency of the
      mutations. RESULTS: The cases of 91 patients in each arm were analyzed. Obstetric
      complications were second trimester abortions (16.5%), intrauterine fetal death
      (53.8%), preeclampsia (8.8%), and severe intrauterine growth restriction (20.9%).
      Study subjects were more likely to be older and multiparous compared with control
      subjects. The 2 groups showed no difference in the incidence of smoking or family
      history of thrombosis, but study subjects were more likely to have a positive
      family history of obstetric complications. The prevalence of factor V Leiden
      (12.1% vs 18.7%; P = .304), prothrombin (7.7% vs 5.5%; P = .765), methylene
      tetrahydrofolate reductase gene mutations (53.8% vs 65.9%; P = .130), and > 1
      mutation (11.0% vs 17.6%; P = .290) was not significantly different between study
      subjects and control subjects. CONCLUSION: Factor V Leiden, prothrombin, and
      methylene tetrahydrofolate reductase gene mutations did not seem to play a
      significant role in adverse pregnancy outcome in our population.

PMID- 17000244
TI  - The Maternal-Fetal Medicine Units Cesarean Registry: safety and efficacy of a
      trial of labor in preterm pregnancy after a prior cesarean delivery.
AB  - OBJECTIVE: This study was undertaken to compare success rates of vaginal birth
      after cesarean (VBAC) delivery, and uterine rupture as well as maternal/perinatal
      outcomes between women with preterm and term pregnancies undergoing trial of
      labor (TOL), and to compare maternal and neonatal morbidities in those women with
      preterm pregnancies undergoing a TOL versus repeat cesarean delivery without
      labor (RCD). STUDY DESIGN: Prospective 4-year observational study of women with a
      singleton gestation and a prior cesarean delivery at 19 academic centers.
      Clinical characteristics, maternal complications and VBAC delivery success for
      those with a preterm (24(0)-36(6) weeks) TOL, preterm RCD and term TOL (> or = 37
      weeks) were analyzed. RESULTS: Among 3119 preterm pregnancies with prior cesarean
      delivery, 2338 (75%) underwent a TOL. 15,331 women undergoing TOL at term were
      also analyzed as a control group. TOL success rates for preterm and term
      pregnancies were similar (72.8% vs 73.3%, P = .64). Rates of uterine rupture
      (0.34% vs 0.74%, P = .03) and dehiscence (0.26% vs 0.67%, P = .02) were lower in
      preterm compared with term TOL. Thromboembolic disease, coagulopathy and
      transfusion were more common in women undergoing a preterm TOL than those at
      term. Among women undergoing a preterm TOL, rates of uterine dehiscence,
      coagulopathy, transfusion, and endometritis were similar to those having a
      preterm RCD. After controlling for gestational age at delivery and race, neonatal
      outcomes such as Neonatal Intensive Care Unit (NICU) admission, intraventricular
      hemorrhage, sepsis, and ventilatory support were similar in both groups except
      for a higher rate of respiratory distress syndrome in those delivered after a
      TOL. CONCLUSION: The likelihood of VBAC success after TOL in preterm pregnancies
      is comparable to term gestations, with a lower risk of uterine rupture. Perinatal
      outcomes are similar with preterm TOL and RCD. TOL should be considered as an
      option for women undergoing preterm delivery with a history of prior cesarean
      delivery.

PMID- 17000245
TI  - The MFMU Cesarean Registry: impact of fetal size on trial of labor success for
      patients with previous cesarean for dystocia.
AB  - OBJECTIVE: The purpose of this study was to determine the influence of change in
      infant birth weight between pregnancies on the outcome of a trial of labor for
      women whose first cesarean delivery was performed for dystocia. STUDY DESIGN:
      Secondary analysis of 7081 patients with 1 previous cesarean delivery and no
      other deliveries after 20 weeks' gestation, undergoing a trial of labor with a
      singleton gestation. Cases were classified as dystocia if the listed indication
      for the cesarean delivery in the first pregnancy was failed induction, cephalo
      pelvic disproportion, failure to progress, or failed forceps or vacuum. Outcomes
      of the trial of labor were correlated with fetal size relative to birth weight in
      the initial pregnancy for those women whose initial cesarean delivery was for
      dystocia and those with other indications. RESULTS: For the cohort being studied
      (n = 7081), dystocia was the indication for the first cesarean delivery for 3182
      (44.9%). Trial of labor resulted in vaginal delivery for 54% of patients whose
      first cesarean delivery was performed for dystocia, compared with 67% for those
      with other indications (P < .01). For those whose first cesarean delivery was for
      dystocia, trial of labor success was correlated with birth weight differences
      between the pregnancies, with only 38% delivering vaginally if the trial of labor
      birth weight exceeded the initial pregnancy birth weight by more than 500 g.
      Using logistic regression and adjusting for other potential confounding factors,
      the odds of success decreased by 3.8% for each increase of 100 g in birth weight
      in the trial of labor relative to the first birth weight. CONCLUSION: For women
      with previous cesarean delivery for dystocia, increasing birth weight in the
      subsequent trial of labor relative to the first birth weight diminishes the
      chances of successful vaginal delivery.

PMID- 17000246
TI  - Vaginal birth after cesarean delivery in twin gestations: a large, nationwide
      sample of deliveries.
AB  - OBJECTIVE: The purpose of this study was to assess the maternal morbidity
      associated with attempted vaginal birth after cesarean (VBAC) in twin gestations
      using a large, nationwide sample of deliveries. STUDY DESIGN: Data for this study
      were obtained from an administrative dataset, the Nationwide Inpatient Sample, a
      representative sample of discharges from non-Federal hospitals, for the years
      1993 to 2002. Patients admitted nonemergently for the delivery of twin gestations
      who had a history of previous cesarean delivery were selected. Patients that
      either delivered vaginally or who had discharge codes that indicated labor before
      cesarean delivery were defined as the trial of labor group, while patients who
      had a cesarean delivery without discharge codes that indicated labor were defined
      as the elective cesarean group. Various complications of delivery were analyzed
      for each group. RESULTS: We identified 4705 women who underwent an elective
      cesarean delivery and 1850 women who underwent a trial of labor. For women who
      had a trial of labor, 836 (45.2%) delivered vaginally. The rate of uterine
      rupture was higher in the trial of labor group than in the elective cesarean
      group (0.9% vs 0.1%, P < .001), and the rate of wound complications was lower
      (0.6% vs 1.3%, P < .02). The rates of other complications including hysterectomy,
      transfusion, major postpartum infection, thromboembolism, uterine dehiscence, and
      pelvic hematoma were not significantly different between the 2 groups.
      CONCLUSION: Our study showed a significantly higher rate of uterine rupture in
      the trial of labor group that is similar to the rates reported for trial of labor
      after cesarean in singleton pregnancies.

PMID- 17000247
TI  - Can uterine rupture in patients attempting vaginal birth after cesarean delivery
      be predicted?
AB  - OBJECTIVE: This study was undertaken to use multivariable methods to develop
      clinical predictive models for the occurrence of uterine rupture by using both
      antepartum and early intrapartum factors. STUDY DESIGN: This was a planned
      secondary analysis from a multicenter case-control study of uterine rupture among
      women attempting vaginal birth after cesarean (VBAC) delivery. Multivariable
      methods were used to develop 2 separate clinical predictive indices--one that
      used only prelabor factors and the other that used both prelabor and early labor
      factors. These indices were also assessed with the use of Receiver operating
      characteristic curves. RESULTS: We identified 134 cases of uterine rupture and
      665 noncases. No single individual factor is sufficiently sensitive or specific
      for clinical prediction of uterine rupture. Likewise, the 2 clinical predictive
      indices were neither sufficiently sensitive nor specific for clinical use
      (receiver operating characteristic curve [area under the curve] 0.67 and 0.70,
      respectively). CONCLUSION: Uterine rupture cannot be predicted with either
      individual or combinations of clinical factors. This has important clinical and
      medical-legal implications.

PMID- 17000248
TI  - Antenatal noninvasive treatment of patients at risk for alloimmune
      thrombocytopenia without a history of intracranial hemorrhage.
AB  - OBJECTIVE: The purpose of this study was to evaluate noninvasive management of
      alloimmune thrombocytopenia that included only the blind administration of
      immunoglobulin. STUDY DESIGN: Seventeen women with 30 pregnancies that were at
      risk of neonatal alloimmune thrombocytopenia were included. Except for 6 cases,
      in which the women refused treatment, 24 pregnancies were managed by the weekly
      administration of intravenous immunoglobulin without monitoring platelet count.
      RESULTS: The mean platelet count at birth after intravenous immunoglobulin
      treatment was 118,000/microL, compared with 25,000/microL among the 17 first
      affected infants and 24,000/microL among the 6 infants whose mothers refused
      treatment (P < .05). Only 8% of the treated fetuses had platelet counts of
      <30,000/microL at birth, compared with 70% of the untreated infants (P < .05).
      None of the treated and nontreated fetuses had an intracranial hemorrhage.
      CONCLUSION: Noninvasive management of alloimmune thrombocytopenia that consists
      of only immunoglobulin administration is highly effective and seems safe in women
      without a history of fetal/neonatal intracranial hemorrhage.

PMID- 17000249
TI  - Anti-D in Rh positive pregnancies.
AB  - OBJECTIVE: The purpose of this study was to review the clinical outcomes of anti
      D isoimmunization in a series of women who typed Rh positive or Rh weak positive.
      STUDY DESIGN: This was a review of The Ohio State University Medical Center Fetal
      Therapy Program Database. RESULTS: Of 1068 pregnancies affected by anti-D, 5
      pregnancies (0.47%) occurred in 4 women between 1994 and 2004, who were
      serologically typed as Rh positive or Rh weak positive. All 5 pregnancies
      delivered at term. All newborns were confirmed affected either by a positive
      direct antiglobulin test (DAT) or were Rh positive. Newborns were not anemic at
      birth and subsequently did not require transfusion. No newborns were treated for
      jaundice. All newborns were discharged home with their mothers. CONCLUSION: Anti
      D hemolytic disease of the fetus and newborn (HDFN) is a rare complication of Rh
      positive and Rh weak positive pregnancies. Although the potential for severe HDFN
      exists in this clinical scenario, our experience suggests that in Rh positive or
      Rh weak positive pregnancies with anti-D isoimmunization, clinical HDFN is mild.
      Nonetheless, Rh positive or Rh weak positive patients with anti-D should be
      monitored for potentially significant HDFN.

PMID- 17000250
TI  - Diagnostic accuracy of noninvasive fetal Rh genotyping from maternal blood--a
      meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to determine the reported diagnostic
      accuracy, the validity, and the current limitations of fetal Rh genotyping from
      peripheral maternal blood based on the existing English-written publications.
      STUDY DESIGN: A search of the English literature describing fetal RhD
      determination from maternal blood was conducted. From each study, we determined
      the number of samples tested, fetal RhD genotype, the source of the fetal DNA
      (maternal plasma, serum, or fetal cells), gestational age, and confirmation of
      fetal Rh type. The presence of alloimmunization and exclusions of tested samples
      were noted. For the meta-analysis we calculated composite estimates using 2
      random effects models, weighted GLM and Bayesian. Sensitivity, specificity,
      positive and negative predictive values were calculated. RESULTS: We identified
      37 English-written publications that included 44 protocols reporting noninvasive
      Rh genotyping using fetal DNA obtained from maternal blood on a total of 3261
      samples. A total of 183 (183/3261, 5.6%) samples were excluded from the meta
      analysis. The overall diagnostic accuracy after exclusions was 94.8%. The
      gestational ages ranged between 8 and 42 weeks gestation. Maternal serum and
      plasma were found to be the best source for accurate diagnosis of fetal RhD type
      in 394/410 (96.1%) and 2293/2377 (96.5%), respectively. There were 719/783
      (91.8%) alloimmunized patients that were correctly diagnosed. There were 16
      studies that reported 100% diagnostic accuracy in their fetal RhD genotyping.
      CONCLUSION: The diagnostic accuracy of noninvasive fetal Rh determination using
      maternal peripheral blood is 94.8%. Its use can be applicable to Rh prophylaxis
      and to the management of Rh alloimmunized pregnancies. Improvements of the
      technique and further study of structure and rearrangements of the RhD gene may
      improve accuracy of testing and enable large-scale, risk-free fetal RhD
      genotyping using maternal blood.

PMID- 17000251
TI  - Impact of the recent randomized trials on the use of progesterone to prevent
      preterm birth: a 2005 follow-up survey.
AB  - OBJECTIVE: The purpose of this study was to determine whether current attitudes
      regarding the use of progesterone to prevent preterm birth have changed since our
      last survey in 2003. STUDY DESIGN: We mailed a 20 question survey to 1264 board
      certified Maternal-Fetal Medicine specialists in the United States between
      February and March of 2005 asking about their use and attitudes regarding
      progesterone to prevent preterm birth. RESULTS: Five hundred and seventy-two
      surveys were returned (response rate of 45%). In 2005, 67% of respondents used
      progesterone to prevent SPTB, compared to 38% in 2003 (P < .001). Among users,
      38% recommended progesterone for indications other than previous SPTB. Users were
      more concerned about lack of insurance coverage compared to nonusers but nonusers
      were more concerned about safety, efficacy, need for more data, and long-term
      neonatal effects. CONCLUSION: Although the use of progesterone to prevent PTB has
      increased significantly since our last survey, there remain a substantial number
      of nonusers. Among users, many are using it for indications not yet proven in
      clinical trials. Current nonusers have higher levels of concerns compared to
      nonusers in the first survey and their major concern is the need for more data.

PMID- 17000252
TI  - Acute and chronic respiratory diseases in pregnancy: associations with placental
      abruption.
AB  - OBJECTIVE: This study was undertaken to examine the associations between maternal
      respiratory diseases and placental abruption. STUDY DESIGN: A population-based,
      retrospective cohort study was conducted to examine the associations between
      maternal respiratory diseases and abruption in the United States. Data on women
      who delivered singleton births (n = 37,314,022) were derived from the National
      Hospital Discharge Survey for the years 1993 to 2003. International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
      codes were used to identify pregnant women hospitalized for acute upper
      respiratory diseases, viral and bacterial pneumonia, acute bronchitis, and acute
      bronchiolitis, chronic bronchitis, asthma, and abruption. Relative risk (RR) and
      95% CI were derived from multivariable logistic regression models to evaluate the
      associations after adjusting for maternal age, race, marital status, smoking,
      cocaine use, adequacy of prenatal care, maternal insurance status, geographic
      location, and year of birth (although data on smoking and cocaine use are likely
      underreported). RESULTS: The rate of abruption was 9.7 per 1,000 singleton
      births. The overall rate for acute respiratory conditions was 2.2 per 1000
      pregnancies. Acute upper respiratory diseases (RR 3.2, 95% CI 3.0-3.4) and
      viral/bacterial pneumonia (RR 2.2, 95% CI 1.9-2.4) were associated with
      abruption. The rate of chronic respiratory conditions was 9.0 per 1,000
      pregnancies. Chronic bronchitis was strongly associated with abruption (RR 31.8,
      95% CI 29.6-34.3), but the association between asthma and abruption was modest
      (RR 1.1, 95% CI 1.0-1.2). Stratified analysis by maternal race showed that asthma
      was associated with abruption among black women but not white women. CONCLUSION:
      Pregnancies complicated by acute and chronic respiratory diseases requiring
      hospitalization are associated with placental abruption.

PMID- 17000253
TI  - Inclusion and exclusion criteria of preterm premature rupture of membranes.

PMID- 17000255
TI  - Evidence-based surgery for cesarean delivery--the historic perspective.

PMID- 17000257
TI  - Evidence-based surgery for cesarean delivery.

PMID- 17000260
TI  - Proper place of laparoscopy in the management of IBS patients.

PMID- 17000261
TI  - Uterine artery embolization versus hysterectomy in the treatment of symptomatic
      uterine fibroids (EMMY trial).

PMID- 17000263
TI  - Occiput posterior fetal head position: not just vacuum assisted deliveries but
      primary prevention.

PMID- 17000267
TI  - Current problems in surgery: gastric cancer.

PMID- 17000269
TI  - Ischemic heart disease: dental management considerations.
AB  - Ischemic heart disease (IHD) is a common problem. Thus, most dental professionals
      who treat adults see patients with IHD on a daily basis. Fortunately, most
      patients are either too young to have clinical stigmata of IHD or have the
      disease well controlled. However, for those patients prone to angina or a
      myocardial infarction, dental care providers must be prepared to recognize and
      manage the risks so untoward events are prevented or their impact mitigated. This
      article presents information useful for assessing risks and planning the delivery
      of safe dental care to those with IHD.

PMID- 17000270
TI  - Valvular heart disease and heart failure: dental management considerations.
AB  - Approximately 5 million people are diagnosed with valvular heart disease in the
      United States each year. Many of these will present to the general dentist for
      routine dental care. The dentist must then understand the implications of this
      disease process to treat these patients safely and effectively. Of course
      patients with pathologic valve disease are managed in close consultation with
      their physicians. Even so, a dentist with knowledge of the disease process, as
      well as its diagnosis and treatment, has greater confidence when treating these
      patients. This article summarizes issues related to valvular heart disease and
      heart failure and provides guidance to dentists treating patients with such
      conditions.

PMID- 17000271
TI  - Dental management of patients with obstructive pulmonary diseases.
AB  - Many dental patients have obstructive pulmonary disease, such as chronic
      bronchitis, emphysema, and bronchial asthma. These diseases have different
      etiologies but may have overlapping signs and symptoms. Diagnosis and treatment
      are becoming more sophisticated so that morbidity and mortality are improving.
      Most dental patients with these morbidity and mortality are improving. Most
      dental patients with these disease can be treated safely with only minor
      adjustments to procedures. Cigarette smoking is a common risk factor that dental
      health care providers can address with a simple program called the five A's.

PMID- 17000272
TI  - Management of the dental patient with renal disease.
AB  - The kidneys are essential organs responsible for a multitude of bodily functions.
      One of the most important roles involves the regulations of intravascular volume
      and concentration of fluids in the body by producing urine. In addition, the
      kidneys are involved in regulation of blood pressure, detoxification of harmful
      substances, secretion of hormones, the control of acid/base balance and
      concentration of several electrolytes, and many other functions. This article
      provides the dental practitioner with a review of the renal system, associated
      pathology, and how one must alter their management to provide effective and safe
      treatment.

PMID- 17000273
TI  - Dental management of patients with hypertension.
AB  - About 50 million people in the United States have hypertension. Many
      epidemiologists feels it is the number one public health problem in developed
      countries. Although asymptomatic early on, untreated hypertension leads to
      cardiovascular disease, strokes, renal failure, and blindness. Dentists no doubt
      treat patients with hypertension and its sequelae in their practice. This article
      summarizes the current thinking on the diagnosis and treatment of this condition,
      emphasizing dental implications. The article presents common oral and systemic
      side effects of antihypertensive medications, and discusses how dentists can help
      treat hypertension through the fabrication of devices useful in reducing
      obstructive sleep apnea.

PMID- 17000274
TI  - Dental management of patients with end-stage liver disease.
AB  - This article presents a review of end-stage chronic liver disease (cirrhosis)
      with emphasis on the clinical presentation, diagnosis, and complications of
      cirrhosis, along with their medical and surgical management and prognosis. This
      article also discusses the evaluation and management of the dental patients with
      cirrhosis, including the implications decreased hepatic function has on drugs
      commonly used in dental treatment.

PMID- 17000275
TI  - Dental management of patients with diabetes.
AB  - Diabetes is a disease of metabolism resulting from impaired insulin secretion,
      varying degrees of insulin resistance, or both. Management of the diabetic dental
      patients must take into consideration the impact of dental disease and dental
      treatment on the management of diabetes as well as an appreciation for the
      comorbidities that accompany long-standing diabetes. Those comorbidities include
      obesity, hypertension, and dyslipidemia. Central to the management of diabetes is
      the intensive regulation of plasma glucose along with management of comorbidities
      comprising the "metabolic syndrome." Management of the diabetic dental patient
      should focus on periodontal health and the delivery of comprehensive dental care
      with minimal disruption of metabolic homeostasis and recognition of diabetic
      comorbidities.

PMID- 17000276
TI  - Management of dental patients with seizure disorders.
AB  - Dental practitioners from time to time must treat patients with epilepsy or
      similar seizure disorders. This article describes the various classification for
      epilepsy, explains how such disorders are evaluated and diagnosed, discusses
      management methods, and addresses related issues for special populations, such as
      pregnant women and elderly. In addition, the article offers information about
      what special steps dentists should take in treating such epileptic patients and
      others vulnerable to seizures and in preparing offices and staff for the
      possibility that a patient will have a seizure in the office. In general, a
      patient with severe, poorly controlled epilepsy should be treated in a hospital.
      Otherwise, a well-controlled patient should easily be treated in the office.

PMID- 17000277
TI  - Dental management of patients with stroke or Alzheimer's disease.
AB  - Dentists are caring for an older population with significant comorbidities. It is
      necessary to be familiar with a patient's medical history and medications and how
      they may affect the care provided. This article focuses on patients with history
      of strokes or Alzheimer's disease.

PMID- 17000278
TI  - HIV-positive patients: dental management considerations.
AB  - HIV infection in humans occurs primarily by mucosal infection during unprotected
      sexual activity or inoculation during intravenous drug use. HIV infection causes
      a progressive deterioration of protective cell-medicated immunity, specifically
      due the destruction of thymus-derived lymphocytes, called T-cell, during viral
      replication. Highly active antiretroviral therapy (HAART) reduces HIV viral
      replication and improves immune function against opportunistic infections, but it
      does not offer a cure for disease. Dental professionals should be able to
      recognize those with HIV infection by identifying the oral manifestations of
      fungal, viral, and bacterial infections or neoplasms that occur with
      immunodeficiency. Dental care providers should understand the adverse effects of
      HAART and communicate the importance of good oral health in managing disease.

PMID- 17000279
TI  - Dental management of patients with bone marrow and solid organ transplantation.
AB  - With advances in transplant science, an increasing number of people are
      undergoing and surviving hematopoietic stem cell and solid organ transplantation.
      Those transplant recipients are also living longer. This means that many dentists
      nowadays will occasionally treat patients who are anticipating or who have
      received a transplant. Dentists thus should be knowledgeable about issues related
      to this population. The dentist's role is important because transplant patients
      are especially vulnerable to infection, which can stem from poor oral and dental
      hygiene. This article provides dentists with an overview of transplant science
      and guidance for dentists treating transplant patients.

PMID- 17000280
TI  - Pregnancy: physiologic changes and considerations for dental patients.
AB  - Human gestation is a period of dynamic physiologic changes designed to support
      the development fetus. Systems affected include the respiratory,
      gastrointestinal, circulatory, and musculoskeletal. These alterations influence
      the patient's general health and make her prone to develop complications unique
      to pregnancy. Such complications include pre-eclampsia, gestation diabetes, and
      pregnancy tumors. The fetus's development is also affected by its mother's
      health, social habits, and medication usage. To protect both the mother and
      unborn child, dental professional may need to incorporate maternal counseling,
      treatment modifications, or changes to their customary medication repertoire.

PMID- 17000281
TI  - Left ventricular encasement after pneumonectomy: case report.

PMID- 17000282
TI  - Presidential address 2003.

PMID- 17000283
TI  - Our destination and our destiny: real endoscopic cardiac surgery.

PMID- 17000284
TI  - Surgical treatment of tumors of the proximal stomach with involvement of the
      distal esophagus: a 26-year experience with Siewert type III tumors.
AB  - OBJECTIVE: A paucity of outcome data exists regarding patients with proximal
      stomach cancer involving the distal esophagus (Siewert type III tumors). This is
      especially true with regard to long-term survival rates after surgical
      intervention. METHODS: Medical records were reviewed of all patients who
      underwent total gastrectomy and distal esophagectomy with Roux-en-Y
      esophagojejunostomy for Siewert type III tumors from January 1975 through
      December 2000. RESULTS: There were 116 patients (93 men and 23 women). The median
      age was 66 years (range, 22-87 years). Pathologic stage was 0 (carcinoma in situ)
      in 1 patient, IB in 13 patients, II in 17 patients, IIIA in 34 patients, IIIB in
      10 patients, and IV in 41 patients. Complete resection was achieved in 69 (59.5%)
      patients. Eleven (9.5%) patients were treated with neoadjuvant therapy, 49
      (42.2%) received adjuvant therapy, and 6 (5.2%) received intraoperative
      radiation. Follow-up was complete in 114 (98.3%) patients, ranging from 1 to 281
      months (median, 14 months). Operative mortality was 5.2%. Complications occurred
      in 51 (43.9%) patients. Clinically significant anastomotic leaks occurred in 15
      (12.9%) patients. Median hospitalization was 13 days (range, 8-70 days). Median
      follow-up was 14 months (range, 1-281 months). Overall median survival was 434
      days, with 1-, 5-, and 10-year survivals of 56.2%, 19.0%, and 13.5%,
      respectively. The only factor associated with increased hospital mortality was
      anastomotic leakage (P = .002). Incomplete resection, increased tumor stage and
      grade, and splenic involvement significantly worsened long-term survival.
      CONCLUSIONS: Total gastrectomy and distal esophagectomy for Siewert type III
      tumors is associated with reasonable mortality and significant morbidity.
      Although often palliative, surgical intervention can provide long-term survival,
      especially in patients with completely resected, early-stage, low-grade tumors.

PMID- 17000285
TI  - Positron emission tomography predicts survival in malignant pleural mesothelioma.
AB  - OBJECTIVES: Recent studies suggest that standard uptake value on
      fluorodeoxyglucose positron emission tomography scan can predict mediastinal
      lymph node status in malignant pleural mesothelioma. Because mediastinal nodal
      metastasis is known to be associated with poor prognosis, we hypothesized that
      standard uptake value on fluorodeoxyglucose positron emission tomography might
      independently predict survival. METHODS: Patients with pathologically proven
      mesothelioma underwent fluorodeoxyglucose positron emission tomography scanning.
      Patients fasted and received a minimum of 10 mCi of F18-fluorodeoxyglucose. Whole
      body emission studies were acquired, followed by whole-body transmission scans
      with iterative reconstruction. On the basis of the maximal chi-square method, a
      standard uptake value of 10 was chosen to classify patients as low versus high
      standard uptake value. Survival probabilities for both standard uptake value
      groups were estimated by the Kaplan-Meier method. A Cox proportional hazards
      model assessed the joint influence of standard uptake value, histology, and stage
      on survival. RESULTS: From 1998 to 2005, 137 patients with malignant pleural
      mesothelioma underwent positron emission tomography scans. The median follow-up
      for all surviving patients was 24 months. Median survivals were 9 and 21 months
      for the high and low standard uptake value groups, respectively (P = .02). In a
      multivariable analysis, high standard uptake value tumors were associated with a
      1.9 times greater risk of death than low standard uptake value tumors (P < .01).
      Mixed histology carried a 2.9 times greater risk of death than epithelioid
      histology (P < .01), and stages III and IV had a 1.8 times greater risk of death
      than stages I and II (P = .05). CONCLUSIONS: Standard uptake value greater than
      10, mixed histology, and stages III and IV are poor risk factors in malignant
      pleural mesothelioma. These findings suggest that fluorodeoxyglucose positron
      emission tomography can be used to stratify patients for treatment and clinical
      trials.

PMID- 17000286
TI  - Radical sublobar resection for small-sized non-small cell lung cancer: a
      multicenter study.
AB  - OBJECTIVE: At present, even when early-stage, small-sized non-small cell lung
      cancers are being increasingly detected, lesser resection has not become the
      treatment of choice. We sought to compare sublobar resection (segmentectomy or
      wedge resection) with lobar resection to test which one is the appropriate
      procedure for such lesions. METHODS: From 1992 to 2001, a nonrandomized study was
      performed in 3 institutes for patients with a peripheral cT1N0M0 non-small cell
      lung cancer of 2 cm or less who were able to tolerate a lobectomy. The results of
      the sublobar resection group enrolled preoperatively (n = 305) were compared with
      those of the lobar resection group (n = 262). RESULTS: Except for distribution of
      tumor location, there were no significant differences in any variable, patient
      characteristics, curability, pathologic stage, morbidity, or recurrence rate.
      Median follow-up was more than 5 years. Disease-free and overall survivals were
      similar in both groups with 5-year survivals of 85.9% and 89.6% for the sublobar
      resection group and 83.4% and 89.1% for the lobar resection group, respectively.
      Multivariate analysis confirmed that the recurrence rate and prognosis associated
      with sublobar resection were not inferior to those obtained with lobar resection.
      Postoperative lung function was significantly better in patients who underwent
      sublobar resection. CONCLUSIONS: Sublobar resection should be considered as an
      alternative for stage IA non-small cell lung cancers 2 cm or less, even in low
      risk patients. These results could lay the foundation for starting randomized
      controlled trials anew, which would bring great changes of lung cancer surgery in
      this era of early detection of lung cancer.

PMID- 17000287
TI  - Endoscopic robotic mitral valve surgery.
AB  - OBJECTIVE: To determine the safety and efficacy of endoscopic mitral valve
      surgery using robotic instruments through the lateral right chest. METHODS: We
      conducted a retrospective review of 127 patients taken to the operating room for
      endoscopic robotic mitral surgery from December 2002 through November 2005. Mean
      age was 54 +/- 13 years and 58% were male. Mitral regurgitation was 4+ in 121
      patients, 3+ in 4 patients, and 2+ in 2 patients. Nineteen (15%) patients had a
      left ventricular ejection fraction of 0.50 or less. Surgical approach was through
      4 right chest ports with femoral perfusion and endoaortic balloon occlusion. Mean
      follow-up was 13.7 +/- 8.9 months and was 100% complete. Echocardiographic follow
      up was available on 98 patients with a mean of 8.4 +/- 8.1 months. RESULTS: The
      mitral procedure was completed endoscopically in 121 (95%) patients. Mitral valve
      repair was performed in 114 patients and mitral valve replacement in 7 patients.
      Two patients required reoperation on the mitral valve. There was 1 (0.8%)
      hospital death and 1 late death. Echocardiographic follow-up in 98 survivors of
      endoscopic mitral repair revealed 0-1+ regurgitation in 95 (96.9%) and 2+ in 3
      (3.1%) patients. CONCLUSIONS: Totally endoscopic mitral surgery can be performed
      safely with robotic instrumentation. A right lateral configuration of the robotic
      system allows excellent visualization of the valve with minimal distortion and
      permits two surgical personnel to participate actively in valve instrumentation.
      In selected patients with mitral valve disease, this surgical approach might
      promote higher rates of valve repair.

PMID- 17000288
TI  - Treatment of postoperative sternal dehiscence with mediastinitis: twenty-four
      year use of a single method.
AB  - OBJECTIVE: Postoperative deep sternal wound infection with dehiscence carries a
      high mortality rate, a high morbidity rate, and a poor cure rate. We developed a
      standard protocol of care to treat this complication, achieving primary closure
      and cure of the infection. METHODS: From January 1, 1981, through May 31, 2005
      (24 years 5 months), we treated 114 patients with dehiscence and mediastinitis.
      The diagnosis was made from 4 to 56 days (mean, 14.5 days) after surgery. Mean
      age was 64.3 years (range, 38-84 years); 79 (69%) were obese, and 48 (42%) had
      diabetes. Ten had previous attempts (1-4) of repair with other methods. Treatment
      entailed (1) debridement without removal of bone, (2) bilateral dissection of
      skin and subcutaneous tissue as one layer, (3) implantation of a staggered double
      tube irrigation-suction system posterior and another one anterior to the sternum,
      (4) lateral reinforcement of the sternum and reclosure with a double wire, and
      (5) a single-layer closure of the subcutaneous tissue and skin. RESULTS: Of 114
      patients, 109 (96%) had mediastinitis, positive for Staphylococcus species in 101
      (92.6%). The cure rate was 98% (112/114); hospital stay was 14 days (range, 12-16
      days), with no deaths. CONCLUSIONS: Use of this standard protocol is effective
      and highly recommended. It spares the sternum, cures the infection, and leaves
      the patient physically functional without the use of soft tissue flaps.

PMID- 17000289
TI  - Temporal disparity in the induction of matrix metalloproteinases and tissue
      inhibitors of metalloproteinases after thoracic aortic aneurysm formation.
AB  - BACKGROUND: An important component of matrix remodeling during thoracic aortic
      aneurysm progression is the balance between matrix metalloproteinases and their
      endogenous inhibitors (tissue inhibitors of metalloproteinases). However, whether
      and to what degree matrix metalloproteinase/tissue inhibitor of
      metalloproteinases profiles change over time with an evolving thoracic aortic
      aneurysm remains unclear. METHODS: Descending thoracic aortic aneurysms were
      induced in mice (FVB strain, 15 minutes of 0.5 mol/L CaCl2 exposure) and followed
      for 24 hours, 72 hours, 1 week, 2 weeks, 4 weeks, or 8 weeks (each group, n =
      13). Thoracic aortic aneurysm size was determined by means of video micrometry,
      and immunoblotting was used to measure aortic matrix metalloproteinase 2, 8, 9,
      and 12 and tissue inhibitor of metalloproteinases 1 and 4 levels (expressed as a
      percentage of control values, n = 13). RESULTS: Increased aortic diameter was
      detected by 72 hours and reached a maximal size at 4 weeks (135% +/- 4% increase
      from baseline, P < .05), which is consistent with thoracic aortic aneurysm
      progression. Active matrix metalloproteinase 8 (collagenase) levels increased at
      72 hours (178% +/- 49%, P < .05 from control), and active matrix
      metalloproteinase 12 (elastase) levels increased by 24 hours (138% +/- 11%, P <
      .05), whereas active matrix metalloproteinase 2 levels increased at 72 hours and
      1 week after thoracic aortic aneurysm induction (72 hours: 158% +/- 12%, 1 week:
      162% +/- 19%; P < .05). At 1 week after thoracic aortic aneurysm induction,
      active matrix metalloproteinase 9 and 12 levels decrease (matrix
      metalloproteinase 9: 55% +/- 5%; matrix metalloproteinase 12: 63% +/- 5%; P <
      .05); however, matrix metalloproteinase 9 and 12 levels were increased from these
      values at 4 and 8 weeks (P < .05). Tissue inhibitor of metalloproteinases 1
      levels were decreased at 1 week (52% +/- 15%, P < .05) and later returned to
      control values, whereas tissue inhibitor of metalloproteinases 4 levels increased
      at the late thoracic aortic aneurysm time points (4 weeks: 278% +/- 46%; 8 weeks:
      213% +/- 40%; P < .05). CONCLUSIONS: These findings show 2 phases of matrix
      metalloproteinase abundance during murine thoracic aortic aneurysm formation. The
      late tissue inhibitor of metalloproteinases 4 increase might explain prevention
      of further aortic dilation past 4 weeks. Unique matrix metalloproteinase/tissue
      inhibitor of metalloproteinases temporal relationships occurred during the
      natural history of thoracic aortic aneurysm progression that might hold both
      diagnostic and therapeutic relevance.

PMID- 17000290
TI  - Apicoaortic valved conduit: potential for progress?
AB  - OBJECTIVE: The number of elderly patients who require aortic valve replacement is
      growing, as is the increase of complicating factors, such as previous coronary
      bypass grafting and atherosclerotic disease of the ascending aorta. An uncommon
      surgical option to aortic valve replacement is the apicoaortic valved conduit. In
      this article the techniques and outcomes of 13 cases of apicoaortic valved
      conduit insertions in high-risk patients are described. METHODS: From 2002
      through 2005, 13 patients (mean age, 75 +/- 8.7 years; 8 men) with severe
      calcific aortic stenosis had insertions of an apicoaortic valved conduit because
      of a porcelain aorta (n = 4), previous coronary bypass grafting (n = 6), or both
      (n = 3). The off-pump technique was used in 9 patients, and a heparinized
      miniextracorporeal circulation system was used in 4 patients. Follow-up time was
      6 to 33 months. RESULTS: Mean intensive care stay was 2 +/- 2.7 days, and mean
      hospital stay was 12 +/- 8 days. The 30-day mortality was 15% (2 patients;
      postoperative days 3 and 28, both caused by myocardial infarction). Mortality
      later than 30 days postoperatively was 23% (3 patients; postoperative day 45
      caused by bilateral pulmonary bleeding because of pneumonia, postoperative day 56
      caused by myocardial infarction, and postoperative day 81 caused by pneumonia).
      The remaining 8 patients were doing well, all in New York Heart Association class
      I or II at follow-up, with echocardiography showing a low gradient over the
      valved conduit. CONCLUSIONS: The apicoaortic valved conduit in high-risk patients
      undergoing aortic valve replacement remains a feasible option, with a substantial
      potential for technical development and progress.

PMID- 17000291
TI  - The effect of diabetes mellitus on patients undergoing coronary surgery: a risk
      adjusted analysis.
AB  - BACKGROUND: Surgical case-mix is seriously worsening, and the results of surgical
      revascularization on high-risk cohorts should be continuously evaluated. This
      study investigates the influence of diabetes mellitus on the short and midterm
      outcome in the modern era of coronary surgery. METHODS AND RESULTS: Patients who
      underwent first-time coronary artery bypass grafting from April 1996 to October
      2003 were classified into diabetic and nondiabetic groups. Data were
      prospectively collected and retrospectively analyzed. A total of 5259 patients
      were studied, and of these 877 (17%) were diabetic. Patients with diabetes were
      more likely to be female, have a higher body mass index, be in an advanced New
      York Heart Association class and Canadian Cardiovascular Society class, have a
      history of congestive heart failure, have a poor ejection fraction, renal
      failure, and more extensive coronary artery disease than the nondiabetic group (P
      < .001 for all). In-hospital mortality was 2.2% and 1% for diabetic and
      nondiabetic patients, respectively; however, diabetes was not found to be an
      independent risk factor for in-hospital mortality (odds ratio = 1.63; 95%
      confidence interval 0.92-2.88; P = .089). Postoperative complications were
      comparable in the two groups, with only renal, neurologic, and gastrointestinal
      complications significantly associated with diabetes (all P < or = .05). There
      was no association between diabetes mellitus and postoperative infective
      complications. Diabetes remained an independent predictor of 5-year mortality
      (hazard ratio 1.55; 95% confidence interval 1.22-1.96; P < .001) and of lower 5
      year cardiac-related event-free survival. CONCLUSION: Despite a worsening cohort,
      diabetic patients could be surgically revascularized with low morbidity and
      mortality, comparable with control patients. The negative effect of diabetes
      mellitus on the longer-term mortality and morbidity remains a problem.

PMID- 17000292
TI  - Different patterns of aortic wall elasticity in patients with Marfan syndrome: a
      noninvasive follow-up study.
AB  - OBJECTIVE: Aortic complications determine the life expectancy of most patients
      with Marfan syndrome. To find out whether there is heterogenous aortic
      involvement among patients and, if there is, to characterize aortic patterns and
      response to long-term beta-blocker therapy, we investigated aortic elastic
      properties before and during beta-blocker treatment. METHODS: In 46 patients with
      Marfan syndrome (age, 17.4 +/- 11.1 years) and 46 healthy control subjects,
      ascending and descending aortic elastic parameters were determined noninvasively
      before and after 39 +/- 16 months of beta-blocker treatment with atenolol.
      RESULTS: Aortic diameters and distensibility distinguished Marfan patients and
      controls with a sensitivity of 85% and a specificity of 87%. Cluster analysis
      revealed 4 patterns of aortic phenotypic expression: (1) reduced ascending aortic
      elasticity (46% of patients), (2) diminished ascending and descending aortic
      elasticity (17%), (3) minimal alterations of ascending and descending aortic
      elasticity (20%), and (4) reduced descending aortic elasticity (17%). During
      follow-up, aortic elastic properties improved in 21 (70%) of 30 patients and
      deteriorated in 9 (30%) irrespective of beta-blocker dosage. Improvement was
      observed in 100% of patients (n = 7; age, 5.3 +/- 4.2 years) with end-diastolic
      aortic root diameters between 20 and 30 mm and in 61% of patients (14/23; age,
      20.5 +/- 10.0 years) with root diameters between 30 and 52 mm. CONCLUSIONS:
      Aortic elastic parameters distinguish between patients with Marfan syndrome and
      healthy controls and show the pattern of regional aortic involvement. Improvement
      or deterioration during follow-up can influence therapeutic decisions to prevent
      aortic dissection and rupture. Young age, small root diameter, and high
      distensibility are favorable prognostic factors.

PMID- 17000293
TI  - Proteomics of cerebral injury in a neonatal model of cardiopulmonary bypass with
      deep hypothermic circulatory arrest.
AB  - OBJECTIVE: Concern over neurologic injury limits safe duration of deep
      hypothermic circulatory arrest (DHCA) in surgery for congenital cardiac disease.
      Proteomics is a novel and powerful technique to study global protein changes in a
      given protein system. Using a neonatal model of cardiopulmonary bypass with DHCA,
      we sought to characterize the protein changes associated with DHCA brain injury.
      METHODS: Ten neonatal piglets were randomized to cardiopulmonary bypass with DHCA
      or sham operation. DHCA animals underwent induction of bypass (100 mL x kg(-1) x
      min(-1)), cooling to 18 degrees C, then DHCA for 60 minutes. Animals were
      rewarmed to normothermia, weaned from bypass, and harvested after 30 minutes off
      bypass. Sham animals underwent sternotomy without further instrumentation. Plasma
      samples were taken before bypass and before harvest. Proteins differentially
      expressed in the cerebral neocortex between the 2 groups were determined by 2
      dimensional differential gel electrophoresis using fluorescent cyanine dyes and
      mass spectrometry. A second group of 4 piglets were similarly randomized and,
      after the experiment, tissues underwent perfusion-fixation for histologic
      examination. RESULTS: Cardiopulmonary bypass with DHCA caused extensive
      histologic and ultrastructural cerebral injury. Proteomic analysis of cerebral
      cortex found 10 protein spots to be differentially expressed; 9 were identified
      by mass spectrometry to represent 6 proteins, including apolipoprotein A-1,
      neurofilament-M protein, and enolase. Decreased expression of plasma
      apolipoprotein A-1 was found in DHCA. CONCLUSIONS: The acute protein changes
      associated with cerebral injury in a neonatal model of cardiopulmonary bypass
      with DHCA have been characterized. These may direct further research aimed at
      attenuating injury seen from cardiopulmonary bypass with DHCA.

PMID- 17000294
TI  - Can pulmonary conduit dysfunction and failure be reduced in infants and children
      less than age 2 years at initial implantation?
AB  - OBJECTIVES: We sought to examine risk factors for pulmonary conduit failure or
      dysfunction in infants less than age 2 years at initial implantation. METHODS:
      From 2002 to 2005, 241 children at 17 institutions were discharged alive after
      initial pulmonary conduit insertion. Initial conduit type was pulmonary allograft
      in 37%, aortic allograft in 29%, bovine jugular venous valved conduit in 25%,
      porcine heterograft in 2%, and decellularized allograft in 7%. Parametric hazard
      analysis determined time-related prevalence and associated risk factors for
      pulmonary conduit intervention and explantation. Serial echocardiographic
      measurements after conduit implant were analyzed by mixed regression models.
      RESULTS: There were 89 first conduit-related interventions after discharge and 37
      initial conduit explants were performed. First conduit intervention occurred at a
      constant rate, with a prevalence of 58% at 3 years from initial implant.
      Pulmonary conduit explantation (30% at 3 years) was characterized by an early
      rising risk, suggesting that catheter-based intervention effectively blunts this
      early initial risk. Common risk-factors for first conduit intervention and
      explantation were smaller conduit Z-score and younger age at initial conduit
      implant, and the presence of pulmonary arborization abnormalities or stenoses.
      Pulmonary conduit peak gradient and regurgitation progressed nonlinearly in all
      patients over time. Gradient progressed more rapidly in children with aortic
      allografts and when initial conduit Z-score was less than +1 or more than +3.
      Pulmonary conduit regurgitation also progressed more rapidly in children with
      initial conduit Z-score greater than +3 and in those without jugular venous
      valved conduits, especially aortic allografts. CONCLUSIONS: Pulmonary conduit
      durability and hemodynamic function in patients undergoing initial conduit
      insertion at less than age 2 years can be improved by using pulmonary conduits
      with Z-scores between +1 and +3.

PMID- 17000295
TI  - Brain oxygen and metabolism during circulatory arrest with intermittent brief
      periods of low-flow cardiopulmonary bypass in newborn piglets.
AB  - OBJECTIVE: We performed this study to determine whether brief intermittent
      periods of low-flow cardiopulmonary bypass during deep hypothermic circulatory
      arrest would improve cortical metabolic status and prolong the "safe" time of
      deep hypothermic circulatory arrest. METHODS: After a 2-hour baseline, newborn
      piglets were placed on cardiopulmonary bypass and cooled to 18 degrees C. The
      animals were then subjected to 80 minutes of deep hypothermic circulatory arrest
      interrupted by 5-minute periods of low-flow cardiopulmonary bypass at either 20
      mL x kg(-1) x min(-1) (LF-20) or 80 mL x kg(-1) x min(-1) (LF-80) during 20, 40,
      60, and 80 minutes of deep hypothermic circulatory arrest. All animals were
      rewarmed, separated from cardiopulmonary bypass, and maintained for 2 hours
      (recovery). The oxygen pressure in the cerebral cortex was measured by the
      quenching of phosphorescence. The extracellular dopamine level in the striatum
      was determined by microdialysis. Results are means +/- SD. RESULTS: Prebypass
      oxygen pressure in the cerebral cortex was 65 +/- 7 mm Hg. During the first 20
      minutes of deep hypothermic circulatory arrest, cortical oxygen pressure
      decreased to 1.3 +/- 0.4 mm Hg. Four successive intermittent periods of LF-20
      increased cortical oxygen pressure to 6.9 +/- 1.2 mm Hg, 6.6 +/- 1.9 mm Hg, 5.3
      +/- 1.6 mm Hg, and 3.1 +/- 1.2 mm Hg. During the intermittent periods of LF-80,
      cortical oxygen pressure increased to 21.1 +/- 5.3 mm Hg, 20.6 +/- 3.7 mm Hg,
      19.5 +/- 3.95 mm Hg, and 20.8 +/- 5.5 mm Hg. A significant increase in
      extracellular dopamine occurred after 45 minutes of deep hypothermic circulatory
      arrest alone, whereas in the groups of LF-20 and LF-80, the increase in dopamine
      did not occur until 52.5 and 60 minutes of deep hypothermic circulatory arrest,
      respectively. CONCLUSIONS: The protective effect of intermittent periods of low
      flow cardiopulmonary bypass during deep hypothermic circulatory arrest is
      dependent on the flow rate. We observed that a flow rate of 80 mL x kg(-1) x min(
      1) improved brain oxygenation and prevented an increase in extracellular dopamine
      release.

PMID- 17000296
TI  - Intermediate-term outcomes of the arterial switch operation for transposition of
      great arteries in neonates: alive but well?
AB  - OBJECTIVES: This interprovincial inception cohort study outlines the operative
      and intermediate outcomes of all neonates at a single institution with a broad
      referral area who underwent the arterial switch operation for transposition of
      great arteries, including complex types. Predictors of outcome are explored.
      METHODS: A total of 88 consecutive neonates underwent the arterial switch
      operation between 1996 and 2004 with full-flow (150 mg/kg/min) cardiopulmonary
      bypass with selective deep hypothermic circulatory arrest. Overall and event-free
      survivals were calculated. Health and neurodevelopment (Bayley Scales of Infant
      Development II) were assessed at 18 to 24 months of age. Univariate and
      multivariate analyses, sensitivity, and specificity were determined to identify
      preoperative, intraoperative, and postoperative factors associated with mental
      and/or motor delay. RESULTS: There was 1 operative mortality (1.1%). At the
      average 4-year follow-up, survival was 98.9% and freedom from reintervention was
      93.2%. Eighty-five children were assessed. Three were excluded because of
      unrelated postoperative diagnoses. For the remaining 82, mean scores were 89 +/-
      17 (49-118) for mental skills and 92 +/- 15 (49-125) for motor skills. Anatomic
      complexity, cardiopulmonary bypass, and deep hypothermic circulatory arrest times
      were not associated with developmental outcome. Preoperative variables of low
      gestational age and high preoperative lactate correctly classified 84.1% of
      mentally and/or motor-delayed children. CONCLUSION: Transposition of great
      arteries, including complex types, can be corrected with low surgical risk and
      good intermediate survival; however, neurodevelopmental outcome is a concern.
      These data suggest that although anatomic complexity may not affect late outcome,
      there may be potentially modifiable preoperative factors that can be optimized to
      improve developmental outcomes.

PMID- 17000297
TI  - Efficacy and safety of right and left atrial ablations on the beating heart with
      irrigated bipolar radiofrequency energy: a long-term animal study.
AB  - OBJECTIVE: The Cox maze procedure is the most effective surgical treatment for
      atrial fibrillation; however, its complexity has limited its clinical utility.
      The purpose of this study was to simplify the procedure by using an irrigated
      bipolar radiofrequency ablation device on the beating heart without
      cardiopulmonary bypass. METHODS: Six domestic pigs underwent median sternotomy.
      The pulmonary veins were circumferentially ablated. Electrical isolation was
      confirmed by pacing. Eight lesions were performed epicardially, and three lesions
      were performed through purse-string sutures with one of the jaws of the device
      introduced into the right atrium. After 30 days, magnetic resonance imaging was
      performed to assess atrial function, pulmonary vein anatomy, and coronary artery
      patency. Cholinergic stimulation and burst pacing were administered to induce
      atrial fibrillation. Histologic assessment of the heart was performed after the
      animal was killed. RESULTS: A modified Cox maze procedure was successfully
      performed with the irrigated bipolar radiofrequency device with no deaths. In
      every instance, the pulmonary veins were electrically isolated. Cholinergic
      stimulation with burst pacing failed to produce atrial fibrillation. Imaging
      studies revealed tricuspid regurgitation without evidence of pulmonary vein
      stenosis, coronary artery stenosis, or intra-atrial thrombus. Total atrial
      ejection fraction was 16.9% +/- 7.5%, a significant reduction. Histologically,
      99% of the lesions were transmural, and there was no evidence of coronary sinus
      injury. CONCLUSION: Lesions on both the right and left atria can be created
      successfully on the beating heart with irrigated bipolar radiofrequency. The
      great majority of lesions with this device were transmural. This device should
      not be used on valvular tissue.

PMID- 17000298
TI  - Drug-eluting stents versus arterial myocardial revascularization in patients with
      diabetes mellitus.
AB  - OBJECTIVE: The introduction of drug-eluting stents significantly reduced
      restenosis and reinterventions in patients undergoing percutaneous coronary
      interventions. This study compares results of Cypher stenting with those of
      surgical arterial revascularization in patients with diabetes mellitus. METHODS:
      From May 2002 through May 2005, 523 consecutive diabetic patients underwent
      myocardial revascularization: 244 underwent percutaneous coronary interventions
      incorporating drug-eluting stents, and 279 were treated surgically. All single
      vessel patients in the surgical group were treated with the left internal
      thoracic artery, and most multivessel patients were treated with 2 internal
      thoracic arteries. After propensity score matching, 2 groups (93 patients each)
      were used to compare the 2 revascularization modalities. RESULTS: The number of
      coronary vessels treated per patient was higher in the surgical group (2.72 vs
      1.75, P < .001). Follow-up ranged between 6 and 42 months (mean, 19 months).
      Overall mortality (early and late) was 3.2% in the surgical group and 2.2% in the
      Cypher group (P = .65). Two-year angina-free survival and reintervention-free
      survival (Kaplan-Meier) of the surgical group were 88% and 95%, respectively,
      compared with 47.8% (P = .001) and 83.6% (P = .01), respectively, in the
      percutaneous coronary intervention group. Cox proportional hazards modeling
      revealed assignment to the Cypher group to be the only predictor of
      reintervention (odds ratio, 3.86; 95% confidence interval, 1.25-11.9). Assignment
      to the Cypher group (hazard ratio, 5.92; 95% confidence interval, 2.96-11.87) and
      insulin treatment (hazard ratio, 2.06; 95% confidence interval, 1.06-4.02) were
      independent predictors of angina recurrence. CONCLUSIONS: The midterm clinical
      outcome of diabetic patients who underwent surgical arterial revascularization is
      better than that of patients undergoing percutaneous coronary intervention
      treated with drug-eluting stents.

PMID- 17000299
TI  - Mesothelium regeneration on acellular bovine pericardia loaded with an angiogenic
      agent (ginsenoside Rg1) successfully reduces postsurgical pericardial adhesions.
AB  - OBJECTIVE: Our objective was to reduce postsurgical pericardial adhesions with
      porous acellular bovine pericardia loaded with ginsenoside Rg1, an angiogenic
      agent isolated from Panax ginseng (the Acellular/Rg1 patch). METHODS: The
      acellular/Rg1 patch was used as a substitute to repair a defect created in the
      pericardium of a rabbit model. A commercially available expanded
      polytetrafluoroethylene patch, the cellular pericardium (the cellular patch), and
      the acellular pericardium without loading Rg1 (the acellular patch) were used as
      controls. The implanted samples were retrieved at 1 and 3 months after surgery (n
      = 5 per group at each time point). RESULTS: It was found that each side of the
      implanted patch could be remesothelialized provided that regeneration of neo
      tissue fibrils occurred initially on its surfaces. Because remesothelialization
      did not take place on the surfaces of the expanded polytetrafluoroethylene and
      cellular patches, moderate to severe adhesions to the lung and epicardium were
      clearly observed. As compared with the cellular patch, the acellular patch
      significantly reduced postsurgical pericardial adhesions, especially on its lung
      side, as a result of remesothelialization. In the presence of Rg1, a faster
      remesothelialization was observed on each side of the acellular/Rg1 patch.
      Therefore, the acellular/Rg1 patch was free of any adhesions to the lung;
      however, there was still a filmy adhesion to the epicardium observed in 3 of the
      5 studied animals at 3 months after surgery, due to incomplete
      remesothelialization. CONCLUSIONS: The acellular/Rg1 patch effectively repaired
      pericardial defects in rabbits and successfully reduced the formation of
      pericardial adhesions.

PMID- 17000300
TI  - Myocardial protection in the failing heart: I. Effect of cardioplegia and the
      beating state under simulated left ventricular restoration.
AB  - OBJECTIVE: Heart failure was induced by cardiac pacing to evaluate myocardial
      flow distribution of the open ventricle during delivery of either cardioplegia or
      in the beating state during simulated left ventricular restoration. METHODS:
      Studies included 5 (pacing-induced) failing pig hearts and 6 control hearts.
      Pacing-induced cardiac failure reduced fractional shortening by approximately
      22%, increased left ventricular end-diastolic diameter by 34%, caused pulmonary
      hypertension (mean blood pressure increased from 12 to 35 mm Hg), and led to
      significant ascites. Global and regional coronary blood flow were measured with
      microspheres during cardiopulmonary bypass at 80 mm Hg perfusion pressure in
      either vented (collapsed) or open (exposure by traction for left ventricular
      restoration) left ventricles during continuous perfusion under either beating
      heart or cardioplegic conditions. RESULTS: In control hearts, venting and
      exposure ventriculotomy did not affect flow. In failing hearts decompressed by
      venting, coronary flow was lower during the beating and cardioplegic delivery
      than during control conditions at the same perfusion pressure of 80 mm Hg. Mean
      cardioplegic flow during ventricular decompression by venting exceeded beating
      flow by 97%. Conversely, traction to increase the ventricular radius during
      exposure ventriculotomy reduced endocardial cardioplegic coronary blood flow by
      64% (from 0.97 to 0.59 mL/[min x g]), whereas the beating state raised
      endocardial flow by 95% (from 0.40 to 0.78 mL/[min x g]). Changing ventricular
      shape changed coronary vascular resistance in failing hearts during beating or
      cardioplegic delivery. CONCLUSIONS: Coronary blood flow alterations occurred only
      in failing hearts when geometry was changed from closed to open state. The
      beating method provided more endocardial flow than cardioplegic delivery during
      ventricular exposure for restoration. Vascular remodeling raised coronary
      vascular resistance in failing hearts, thereby requiring higher pressure for
      similar blood flows.

PMID- 17000301
TI  - Myocardial protection in the failing heart: II. Effect of pulsatile cardioplegic
      perfusion under simulated left ventricular restoration.
AB  - OBJECTIVE: The open ventricle was studied in pacing-induced experimental heart
      failure to determine the extent of coronary perfusion and distribution during
      either continuous or pulsatile cardioplegic perfusion compared with whole blood
      in the beating heart. METHODS: In 5 animals that underwent pacing-induced heart
      failure and in 6 control swine, regional coronary blood flows were measured on
      bypass in the open left ventricle (simulating exposure for left ventricle
      restoration) during (1) beating, (2) nonpulsatile cardioplegia, and (3) pulsatile
      cardioplegia modalities. Mean perfusion pressure was maintained at 80 mm Hg.
      RESULTS: Flow magnitude and distribution differed in control and failing hearts
      in the open left ventricle. In control hearts, transmural and endocardial
      cardioplegic flow of nonpulsatile and pulsatile flow (which were similar to each
      other) exceeded beating flow by 63% and 70%, respectively, in the open left
      ventricle condition. Transmural and subendocardial vascular resistance increased
      in failing hearts during cardioplegic delivery, resulting in lower subendocardial
      flow under nonpulsatile conditions for the same perfusion pressure. In failing
      hearts, subendocardial perfusion conditions did not change in the beating state
      (0.89 vs 0.78 mL/min/g in control and failing open beating states, respectively),
      but nonpulsatile cardioplegic flow was significantly reduced by 154%, and became
      lower than beating flow by 32.2% (0.78 vs 0.59 mL/min/g). Conversely, pulsatile
      cardioplegic delivery improved endocardial flow in the open failing hearts, as
      cardioplegic perfusion with pulsatility exceeded beating flow by 41%. In heart
      failure, pulsatility from either the beating heart, which causes extrinsic
      compression of coronary vessels, or intrinsic vessel distension during pulsatile
      cardioplegic perfusion preserved endocardial perfusion better than nonpulsatile
      cardioplegia at the same perfusion pressure. CONCLUSION: In the failing open
      ventricle (simulated geometry during ventricular restoration), subendocardial
      blood flow was maintained in the beating state, but decreased significantly from
      control values during nonpulsatile cardioplegic perfusion. Conversely, pulsatile
      cardioplegic delivery improved subendocardial perfusion of the open failing
      ventricle. These findings of improved subendocardial perfusion during pulsatile
      delivery (either during beating or cardioplegic perfusion) compared with
      nonpulsatile cardioplegic delivery may have important implications for myocardial
      protection in failing hearts.

PMID- 17000302
TI  - A combination of omental flap and growth factor therapy induces arteriogenesis
      and increases myocardial perfusion in chronic myocardial ischemia: evolving
      concept of biologic coronary artery bypass grafting.
AB  - OBJECTIVE: The purpose of this study was to evaluate the therapeutic efficacy of
      the combined growth factor therapy with an omental flap in a rabbit model of
      chronic myocardial ischemia. METHODS: Chronic ischemia was created in rabbits by
      placing a constrictor on the left circumflex artery. Four weeks later the animals
      were divided into 3 groups: group FG, in which a gelatin hydrogel sheet
      incorporating 100 microg of basic fibroblast growth factor was placed over the
      left circumflex region followed by covering with the omental flap including the
      intact gastroepiploic artery; group F, in which only the basic fibroblast growth
      factor sheet was placed; and group N, in which no treatment was done. RESULTS:
      Cine magnetic resonance imaging analysis showed a greater percentage wall
      thickening in the left circumflex region in group FG than in other groups (group
      FG, 49.2% +/- 4.5%; group F, 41.2% +/- 3.8%; group N, 32.1% +/- 2.5%, P =.035,
      group FG vs group F). A colored microsphere assay showed higher perfusion in the
      left circumflex region in group FG than in group F. Perfusion in the left
      circumflex region was decreased after clamping the gastroepiploic artery pedicle
      in group FG (before clamping, 2.83 +/- 0.72 mL x min(-1) x g(-1); after clamping,
      1.93 +/- 0.59 mL x min(-1) x g(-1); P < .01). In vivo angiography via
      gastroepiploic artery showed direct "to-and-fro" visible collaterals between the
      gastroepiploic and occluded left circumflex coronary arteries in group FG.
      CONCLUSION: The combined growth factor therapy with an omental flap induced
      arteriogenesis and provided additional perfusion via the gastroepiploic artery to
      ameliorate regional dysfunction in the chronically ischemic myocardium.

PMID- 17000303
TI  - Strain-related regional alterations of calcium-handling proteins in myocardial
      remodeling.
AB  - BACKGROUND: Cardiac remodeling has been shown to have deleterious effects at both
      the global and local levels. The objective of this study is to investigate the
      role of strain in the initiation of structural and functional changes of
      myocardial tissue and its relation to alteration of calcium-handling proteins
      during cardiac remodeling after myocardial infarction. METHODS: Sixteen
      sonomicrometry transducers were placed in the left ventricular free wall of 9
      sheep to measure the regional strain in the infarct, adjacent, and remote
      myocardial regions. Hemodynamic, echocardiographic, and sonomicrometry data were
      collected before myocardial infarction, after infarction, and 2, 6, and 8 weeks
      after infarction. Regional myocardial tissues were collected for calcium-handling
      proteins at the end study. RESULTS: At time of termination, end-systolic strains
      in 3 regionally distinct zones (remote, adjacent, and infarct) of myocardium were
      measured to be -14.65 +/- 1.13, -5.11 +/- 0.60 (P < or = .05), and 0.92 +/- 0.56
      (P < or = .05), respectively. The regional end-systolic strain correlated
      strongly with the abundance of 2 major calcium-handling proteins: sarcoplasmic
      reticulum Ca2+ adenosine triphosphatase subtype 2a (r2 = 0.68, P < or = .05) and
      phospholamban (r2 = 0.50, P < or = .05). A lesser degree of correlation was
      observed between the systolic strain and the abundance of sodium/calcium
      exchanger type 1 protein (r2 = 0.17, P < or = .05). CONCLUSIONS: Regional strain
      differences can be defined in the different myocardial regions during
      postinfarction cardiac remodeling. These differences in regional strain drive
      regionally distinct alterations in calcium-handling protein expression.

PMID- 17000304
TI  - Aprotinin use in thoracic aortic surgery: safety and outcomes.
AB  - OBJECTIVES: Previous studies of aprotinin use in thoracic aortic surgery, limited
      in size and design, reported minimal information regarding outcomes other than
      blood loss and transfusion. The evaluation of impact of aprotinin on surgical
      outcomes in a large sample is needed. METHODS: Patients at Yale New Haven
      Hospital undergoing thoracic aortic surgery (aneurysm repair, dissections,
      penetrating ulcers, intramural hematomas) between 1995 and 2003 were considered
      for inclusion. Each patient receiving aprotinin was matched to a control per
      preoperative profile (age, gender, urgency of surgery, dissection/location of
      aortic disease). Data (surgical specifics, demographic variables, comorbidities,
      disease location-related variables, preoperative medications, intraoperative
      medications, surgical/operative data) were abstracted from the records of
      successfully matched aprotinin-treated patients and controls (n = 168).
      Comparison and determination of success of matching were performed using
      bivariate analyses. Outcome variables were compared using statistical tests for
      paired data. Supplementary unpaired and regression analyses were also performed.
      RESULTS: Baseline demographics of groups were similar, although controls had
      reduced history of aortic disease, but greater intraoperative use of lysine
      analogs (P < .05). Aprotinin significantly reduced platelet transfusion (P <
      .05). Paired bivariate analyses showed a tendency toward reduced ventilation
      time, pulmonary complications, and permanent arrhythmias (P < .05) associated
      with aprotinin. Supplementary analyses were supportive only for pulmonary
      complications and permanent arrhythmias. CONCLUSIONS: The current evaluation
      substantiates previous reports that aprotinin may be safe to use and likely to
      improve some outcomes of thoracic aortic surgery. However, further studies for
      rare safety and efficacy end points are warranted.

PMID- 17000305
TI  - Grafted skeletal myoblast sheets attenuate myocardial remodeling in pacing
      induced canine heart failure model.
AB  - OBJECTIVE: To overcome problems related to the intramyocardial injection of
      cells, including cell loss and a limited graft area, we developed a cell delivery
      system that uses tissue-engineered myoblast grafts grown as sheets. Here, we
      assessed the feasibility and efficacy of our method in a canine dilated
      cardiomyopathy model. METHODS: Skeletal myoblasts were incubated on temperature
      responsive culture dishes, and the sheets of cells were detached by decreasing
      the temperature. Twelve dogs were given continuous ventricular pacing at 230
      beats/min for 4 weeks; then the myoblast sheets (n = 5) were grafted onto the
      left ventricular wall or a sham operation was performed (n = 7). The number of
      cells was adjusted to 1.5 approximately 2.5 x 10(6) cells per graft, and each dog
      received approximately 20 grafts. RESULTS: The cell sheets were easily grafted
      onto a large area of the left ventricular surface, and there were no serious
      sequelae. Four weeks after graft implantation, echocardiography demonstrated that
      the left ventricular ejection fraction (graft, 26.0% +/- 5.6%; control, 19.5% +/-
      6.8%; P < .05) and fractional shortening (graft, 17.9% +/- 3.6%; control, 7.8% +/
      2.1%; P < .05) were significantly ameliorated with reduced left ventricular
      dilatation (graft, 7.3 +/- 1.3 cm2; control, 10.2 +/- 0.4 cm2; P < .05) and
      increased wall thickness (graft, 5.6 +/- 0.7 mm; control, 4.4 +/- 0.6 mm; P <
      .05). Histologic evidence indicated the grafted myoblasts had survived,
      accompanied by a significant reduction in fibrosis and apoptosis, and a
      significant increase in proliferation. CONCLUSIONS: Grafting of skeletal myoblast
      sheets attenuated cardiac remodeling and improved cardiac performance. This novel
      method was feasible and effective in a large animal model, suggesting an
      innovative and promising strategy for treating patients with end-stage dilated
      cardiomyopathy.

PMID- 17000306
TI  - Pharmacologic relaxation of vein grafts is beneficial compared with pressure
      distention caused by upregulation of endothelial nitric oxide synthase and nitric
      oxide production.
AB  - OBJECTIVE: Pressure distention of veins during preparation for bypass surgery is
      believed to impair vascular integrity and reduce graft patency. We previously
      suggested a combination of pharmacologic vasodilatators as an alternative to
      distention. Vascular homeostasis is largely regulated by nitric oxide. We
      investigated the role of distention in comparison with pharmacologic
      vasorelaxation in the regulation of nitric oxide synthases, nitric oxide
      bioavailability, and vascular reactivity in vein grafts. METHODS: In a porcine
      model the internal jugular vein from either side received pressure distention or
      the combination of vasodilators (alpha-adrenergic antagonist, phenoxybenzamine,
      10 micromol/L; Rho-kinase inhibitor, HA-1077 [fasudil], 50 mumol/L; calcium
      blocker, nicardipine, 1 micromol/L) and then was grafted into the carotid artery.
      Regulation of nitric oxide synthase, as well as nitrate and nitrite levels, were
      examined in vein grafts after 2 weeks of implantation. RESULTS: Distention of
      jugular veins resulted in reduction of vasoconstriction in response to
      depolarization and agonist stimulation. Arterial grafting doubled inducible
      nitric oxide synthase expression in both grafts but caused a pronounced
      upregulation of endothelial nitric oxide synthase protein (by 57.3% +/- 5%) only
      in drug-treated grafts, whereas in distended grafts the endothelial nitric oxide
      synthase level was decreased by 27.5% +/- 2.7%. The downregulated endothelial
      nitric oxide synthase level in the distended grafts was accompanied by a 45.2% +/
      3.1% reduction of phospho-endothelial nitric oxide synthase Ser1177 levels and
      by a significant reduction in nitric oxide synthase activity (12.1% +/- 1.2%) and
      nitrate production (48.9% +/- 5.6%) in comparison with that seen in drug-treated
      grafts. CONCLUSIONS: Pharmacologic preparation of the vein grafts results in
      upregulation of endothelial nitric oxide synthase and increased nitric oxide
      production in the vein grafts after arterial implantation. This might provide
      greater clinical benefit than conventional pressure-distention methods.

PMID- 17000307
TI  - Retrograde cerebral perfusion with intermittent pressure augmentation provides
      adequate neuroprotection: diffusion- and perfusion-weighted magnetic resonance
      imaging study in an experimental canine model.
AB  - OBJECTIVE: Diffusion- and perfusion-weighted magnetic resonance imaging can
      identify ischemic brain injury in the hyperacute stage. For neuroprotection
      during thoracic aortic surgery, we developed a novel retrograde cerebral
      perfusion with intermittent pressure augmentation. The purpose of this study was
      to assess the efficiency of this novel method for neuroprotection in real time by
      using diffusion- and perfusion-weighted magnetic resonance imaging. METHODS:
      Sixteen beagle dogs were randomly divided into 4 groups: the antegrade selective
      cerebral perfusion group (n = 4; antegrade selective cerebral perfusion at a flow
      rate of 10 mL x kg(-1) x min(-1)); the intermittent retrograde cerebral perfusion
      group (n = 4; retrograde cerebral perfusion at a baseline pressure of 15 mm Hg
      with intermittent pressure augmentation to 45 mm Hg every 30 seconds); the
      conventional retrograde cerebral perfusion group (n = 4; conventional retrograde
      cerebral perfusion at a fixed pressure of 25 mm Hg); and the circulatory arrest
      group (n = 4; only circulatory arrest). Diffusion- and perfusion-weighted
      magnetic resonance images were acquired during each session of cerebral
      perfusion. Regions of interest were defined, and the apparent diffusion
      coefficient and relative regional cerebral blood volume were calculated in these
      regions of interest. Finally, the brain was evaluated for its histopathologic
      damage score. RESULTS: The best apparent diffusion coefficient values were
      observed in the intermittent retrograde cerebral perfusion group in all the
      regions of interest, although the relative regional cerebral blood volume values
      were mostly lower than those in the antegrade selective cerebral perfusion group.
      The total Histopathologic Damage Score (0, normal; 32, worst) in the intermittent
      retrograde cerebral perfusion group (8.0 +/- 0.6) was significantly lower than
      that in the conventional retrograde cerebral perfusion (17.5 +/- 1.7; P < .01)
      and circulatory arrest (25 +/- 1.0; P < 0.01) groups and was equivalent to that
      in the antegrade selective cerebral perfusion group (7.8 +/- 0.8; P = .9).
      CONCLUSION: Intermittent retrograde cerebral perfusion provides adequate
      neuroprotection by allowing high apparent diffusion coefficient values to be
      maintained.

PMID- 17000308
TI  - Nonviral gene transfer of hepatocyte growth factor attenuates neurologic injury
      after spinal cord ischemia in rabbits.
AB  - OBJECTIVE: Paraplegia caused by spinal cord ischemia remains a serious
      complication after surgical repair of thoracoabdminal aortic aneurysms.
      Hepatocyte growth factor is a potent angiogenic and neurotrophic factor. We
      sought to investigate the neuroprotective effect of gene transfer of hepatocyte
      growth factor on spinal cord ischemia in rabbits. METHODS: Human hepatocyte
      growth factor expression plasmid was combined with hemagglutinating virus of
      Japan envelope vector. Hemagglutinating virus of Japan envelope vector containing
      the hepatocyte growth factor gene was injected intrathecally into the
      experimental rabbits, whereas control vector or saline was given to the control
      animals. Five days later, spinal cord ischemia was induced by means of infrarenal
      aortic occlusion for 30 minutes. Hind-limb motor function was assessed during a
      14-day recovery period with Tarlov criteria. RESULTS: Human hepatocyte growth
      factor was detected in the cerebrospinal fluid 3 days after gene transfer, and
      the level peaked on day 5. Compared with the control animals, hepatocyte growth
      factor gene transfer significantly increased the capillary density in the gray
      matter and decreased the spinal cord edema. All rabbits pretreated with saline or
      control vector had hind-limb paraplegia (Tarlov score = 0) 14 days after spinal
      cord ischemia. However, previous transfection of the hepatocyte growth factor
      gene remarkably enhanced the Tarlov scores, and 8 of the 9 rabbits showed normal
      motor function (Tarlov score = 5) after a 14-day recovery period. Histologic
      examination showed that the intact motor neurons were preserved to a much greater
      extent in the rabbits transfected with the hepatocyte growth factor gene.
      CONCLUSION: Gene transfer of hepatocyte growth factor attenuates neurologic
      injury after spinal cord ischemia.

PMID- 17000309
TI  - Aprotinin improves cerebral protection: evidence from a survival porcine model.
AB  - OBJECTIVE: Aprotinin is a serine protease inhibitor used during cardiac surgery
      to reduce blood loss and preserve platelet function. It has also been shown to
      reduce leukocyte activation during and after cardiopulmonary bypass. The goal of
      the study was to test the hypothesis that aprotinin could reduce cerebral injury
      after low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest.
      METHODS: Sixteen piglets (mean weight, 13.6 +/- 1.3 kg) were randomly assigned to
      receive aprotinin or placebo (8 animals per group) before a 120-minute period of
      deep hypothermic circulatory arrest (15 degrees C) or 25 mL x kg(-1) x min(-1)
      low-flow cardiopulmonary bypass (25 degrees C or 34 degrees C). Piglets had a
      cranial window placed over the parietal cerebral cortex for direct examination of
      the microcirculation by means of intravital microscopy. Rhodamine-stained
      leukocytes were observed in postcapillary venules, with analysis for adhesion and
      rolling. Plasma was labeled with fluorescein isothiocyanate-dextran for
      assessment of functional capillary density. Neurologic and histologic scores were
      used as the primary outcome measures. RESULTS: During rewarming, the mean number
      of both rolling and adherent leukocytes was significantly lower after aprotinin
      administration (P < .05). At 5 and 15 minutes of rewarming, functional capillary
      density recovered faster with aprotinin treatment (P < .05). Functional outcome
      (neurologic deficit score) on postoperative day 1 was significantly improved in
      aprotinin-treated piglets (P < .05). CONCLUSIONS: Aprotinin reduces inflammation
      and improves neurologic outcome after a prolonged period of deep hypothermic
      circulatory arrest or low-flow cardiopulmonary bypass.

PMID- 17000310
TI  - Extended use of extracorporeal membrane oxygenation after lung transplantation.
AB  - OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) for severe graft failure
      after lung transplantation is accepted immediately postoperatively; extending its
      use is controversial. We evaluated our post-lung transplant ECMO experience,
      which included extended indication, to (1) determine its prevalence, risk
      factors, indications, and timing, (2) compare complications and outcomes of these
      patients with those not requiring it, and (3) identify risk factors, including
      indications, for mortality. METHODS: From February 1990 to October 2005, 474
      patients underwent lung transplantation; postoperative ECMO support was
      instituted for severe graft failure 23 times in 22 patients (4.0%). Indications
      for ECMO and its timing were obtained by reviewing medical records and survival
      by systematic follow-up. RESULTS: No factor evaluated predicted severe graft
      failure leading to ECMO. The most common indication for ECMO was early graft
      failure (13 patients); however, it was also used for pneumonia or sepsis (6) and
      acute rejection (4). ECMO was initiated at a median arterial oxygen
      tension/inspired oxygen fraction of 59 at a median of 2 days postoperatively and
      was maintained for a median of 4 days. The most common complications were renal
      failure (57%) and bleeding (43%). ECMO was effective in salvaging patients with
      rejection and early graft failure (survival at 1, 3, 6, and 12 months: 62%, 54%,
      49%, and 41%), but ineffective for pneumonia or sepsis (survival at these
      intervals: 9%, 4%, 4%, and 3%). CONCLUSIONS: ECMO can be extended beyond early
      severe graft failure to acute rejection and can be considered after the immediate
      postoperative period. Survival after ECMO in patients with pneumonia or sepsis is
      poor.

PMID- 17000311
TI  - Late-stage, nonanastomotic rupture of double-velour Dacron graft after descending
      aortic replacement.

PMID- 17000312
TI  - Complex reconstruction of the thoracic aorta using a novel stent graft/graft
      prosthesis.

PMID- 17000313
TI  - A rare case of acute necrotizing eosinophilic myocarditis: bridge to recovery
      with ventricular assist device support.

PMID- 17000314
TI  - Left internal thoracic artery patch aortoplasty for repair of coarctation of the
      aorta.

PMID- 17000315
TI  - Challenges in early cardiothoracic surgery: aortic homograft transplantation in
      coarctation, a 44-year follow-up.

PMID- 17000316
TI  - Repair of anomalous right and circumflex coronary arteries arising from the
      pulmonary artery.

PMID- 17000317
TI  - Bronchogenic cyst: unexpected finding in a large aneurysm of the pars membranacea
      septi.

PMID- 17000318
TI  - Coronary artery bypass grafting and biventricular pacing efficacy: do past trials
      dictate a change in future practice?

PMID- 17000319
TI  - Mediastinal paraganglioma: utility of preoperative cardiac magnetic resonance
      imaging.

PMID- 17000320
TI  - Telescoping bronchial anastomosis for extended sleeve lobectomy.

PMID- 17000321
TI  - Simultaneous heart valve replacement and reconstruction of the radiation-damaged
      chest wall with a delayed vertical rectus abdominis myocutaneous flap.

PMID- 17000322
TI  - Combined bronchial sleeve resection and repair of partial anomalous pulmonary
      venous return.

PMID- 17000323
TI  - Primary pulmonary plasmacytoma with immunoglobulin G/lambda light chain
      monoclonal gammopathy.

PMID- 17000324
TI  - Large chondrosarcoma of the rib invading the mediastinum and the spine.

PMID- 17000326
TI  - Candidate gene association analysis of thoracic aortic aneurysm and dissection.

PMID- 17000327
TI  - Placement of the Impella Recover LD microaxial blood pump through a bioprosthesis
      is technically feasible.

PMID- 17000328
TI  - Off-pump pulmonary valve implantation.

PMID- 17000330
TI  - Tracheal stents in patients with malignancy.

PMID- 17000333
TI  - Parkinson's disease: background, diagnosis, and initial management.
AB  - Parkinson's disease is a common neurodegenerative disorder associated with aging.
      After essential tremor, it is the most common movement disorder of the elderly.
      Parkinson's disease is the most common disabling movement disorder. This article
      reviews the major clinical features, differential diagnosis, approach to
      diagnosis, and initial management of Parkinson's disease.

PMID- 17000334
TI  - Medical management of advanced Parkinson's disease.
AB  - The management of advancing Parkinson's disease (PD) is a daunting task,
      complicated by dynamic medication responses, side effects, and treatment
      refractory symptoms in an aging patient population. The motor and nonmotor
      complications of advancing PD are reviewed, and practical treatment strategies
      are provided. Careful assessment in the context of the known natural history of
      advancing PD and rational treatment choices can create significant improvement in
      the lives of patients who have advancing PD.

PMID- 17000335
TI  - Cognitive, affective, and psychiatric features of Parkinson's disease.
AB  - Nonmotor symptoms, including cognitive deterioration and dementia, depression and
      apathy, and psychosis, are common in Parkinson's disease. Their presence is
      associated with a tremendous burden for the patient and family members. This
      article reviews the pathophysiololgy, risks, impact, major features, diagnosis,
      and treatment of these symptoms in Parkinson's disease.

PMID- 17000336
TI  - Postural control, gait, and dopamine functions in parkinsonian movement
      disorders.
AB  - Balance impairments and falls, which are common in patients who have parkinsonian
      movement disorders, are a serious threat to the health of these individuals.
      However, the underlying mechanisms cannot be fully explained by presynaptic
      dopaminergic denervation, because balance impairment is at least responsive to L
      dopa therapy. This article reviews the latest clinically relevant literature
      relating postural control, gait, and dopamine in patients who have parkinsonian
      movement disorders.

PMID- 17000337
TI  - Surgical treatment of movement disorders.
AB  - A substantial body of evidence has accumulated regarding the efficacy and safety
      of neurosurgery for Parkinson's disease, essential tremor, and dystonia. Surgery
      for movement disorders (thalamotomy, pallidotomy, and subthalamic nucleotomy or
      subthalamotomy) was largely ablative (lesion-based). Given the safety and anatomy
      preservation advantage, long-term electrical stimulation of these same targets
      (thalamus, globus pallidus, and subthalamic nucleus) is discussed as the
      treatment of choice. High-frequency deep brain stimulation procedures replicate
      the effects of ablative interventions, but do not require making a destructive
      brain lesion. This article outlines patient eligibility for surgery, targeting
      techniques, intraoperative findings, and potential complications and discusses
      the outcomes expected for each of the major interventions for which clinical
      trial data are available.

PMID- 17000338
TI  - Parkinsonian syndromes.
AB  - The term parkinsonian syndromes refers to a group of disorders whose clinical
      features overlap those of idiopathic Parkinson's disease. The four major entities
      include three important neurodegenerations, multiple system atrophy, progressive
      supranuclear palsy, and corticobasal degeneration, and a lacunar cerebrovascular
      disorder, vascular parkinsonism. This article reviews the epidemiology,
      pathology, clinical features, diagnosis, and management of these disorders.

PMID- 17000339
TI  - Essential tremor.
AB  - Essential tremor (ET) is among the most common neurologic disorders. The
      traditional view of this disorder as a benign, monosymptomatic, familial
      condition is being replaced by a more complex view of ET as perhaps a family of
      diseases with etiologic, clinical, and pathologic heterogeneity. This article
      discusses the major clinical features of ET and approaches to its diagnosis and
      treatment.

PMID- 17000340
TI  - Ataxias.
AB  - Gait disorders in elderly individuals are a major cause of falls and their
      attendant morbidities. Ataxia is one of the neurologic components of fall risk,
      as are inattention or confusion, visual impairment, vestibular impairment,
      subcortical white matter disease, parkinsonism, weakness, sensory loss,
      orthostasis or arrhythmia with alterations in blood pressure, pain, medication
      use, and environmental hazards. Ataxia in the geriatric population has many
      causes. Correctly identifying them can improve clinicians' ability to offer
      treatment and management strategies to patients and their families. The goals
      should be safe mobility and preserved activities of daily living.

PMID- 17000341
TI  - Geriatric chorea.
AB  - The differential diagnosis, diagnostic evaluation, and treatment of late-onset
      chorea are reviewed. Late-onset chorea is rare and has a heterogeneous causation.
      A systematic approach to geriatric chorea greatly enhances a correct diagnosis.
      An accurate diagnosis is important because many causes of chorea are treatable or
      or, when heritable, may have significant implications for subsequent generations.
      Most late-onset chorea is either nonlimiting, requiring no treatment, has a
      spontaneous remission, or responds to medication. In a minority of patients,
      chorea is medically refractory or manifestation of an untreatable disorder.

PMID- 17000342
TI  - Dystonia.
AB  - Dystonia is a disorder of involuntary sustained muscle contractions. It is
      commonly classified by age of onset, distribution of involved body regions, and
      etiology. The pathophysiolgy of this condition is complex and imperfectly
      understood. This article reviews the epidemiology, genetics, clinical features,
      and approach to diagnosis and treatment of dystonia.

PMID- 17000343
TI  - Tardive syndromes in the elderly.
AB  - Tardive syndromes are characterized by abnormal involuntary movements that occur
      after prolonged exposure to drugs that block dopamine receptors. The prevalence
      and incidence of tardive syndromes are much higher in elderly individuals, and
      the number of elderly patients receiving antipsychotics has been increasing. This
      article summarizes the clinical phenomenology, pathophysiology, epidemiology, and
      treatment of these disorders in elderly individuals.

PMID- 17000344
TI  - Normal pressure hydrocephalus.
AB  - Normal pressure hydrocephalus (NPH) is a reversible disorder characterized by
      gait impairment, subcortical dementia, and urinary urgency and incontinence
      associated with impaired cerebrospinal fluid circulation and ventriculomegaly.
      Treatment with shunt surgery is most likely to increase mobility, and may also
      improve dementia and urinary symptoms. An international, independent study group
      recently published guidelines for the diagnosis and management of idiopathic NPH.
      This article helps geriatricians identify patients who might have NPH, and care
      for these patients after shunt placement.

PMID- 17000345
TI  - Hospice through the eyes of a radiation oncologist.

PMID- 17000346
TI  - Stability and compatibility of a meperidine-clonidine mixture in portable pump
      reservoirs for the management of cancer pain syndromes.

PMID- 17000347
TI  - Symptom distress and quality-of-life assessment at the end of life: the role of
      proxy response.
AB  - This study sought to advance understanding of the relationships among proxy and
      patient reports of symptom distress and quality of life (QOL). English-speaking
      adults (n=86), their nurses (n=86), and family caregivers (n=49) from 11
      hospice/palliative care organizations completed the Memorial Symptom Assessment
      Scale (MSAS) and McGill Quality of Life Questionnaire (MQOL) at
      hospice/palliative care enrollment, at 1 week, 2 weeks, then monthly until death
      or discharge. Patients and proxies provided similar average reports of symptom
      distress, both physical and psychological, but MSAS correlations were generally
      poor. MQOL correlations were higher for nurse-patient than for patient-caregiver
      dyads. Based on small differences between ratings but only moderate levels of
      correlation, proxy response appears to be a fair substitute for patient response,
      suggesting that symptom and QOL reports should be obtained from all available
      respondents throughout the course of clinical care or research in the
      hospice/palliative care setting.

PMID- 17000348
TI  - Fatigue and depression in cancer patients undergoing chemotherapy: an emotion
      approach.
AB  - Fatigue and depressive symptoms are common in cancer patients, but the nature of
      the relationship between the two remains unclear. We examined the degree to which
      two dimensions of emotion assessed as psychological factors (i.e., arousal and
      valence) predicted changes in fatigue and depressive symptoms over four cycles of
      chemotherapy in cancer patients who participated in a randomized clinical trial.
      Among 549 patients enrolled in the study, 525 provided data from a minimum of two
      treatments and were included in the multilevel modeling analyses. Multilevel
      models were used to identify significant predictors of initial levels and changes
      of fatigue and depressive symptoms and to determine the relationship between
      fatigue and depressive symptoms independent of other predictors proposed in this
      study. Multiple factors, including age, gender, and cancer site, predicted the
      initial levels. More importantly, the two dimensions of psychological factors
      significantly predicted changes in fatigue and depressive symptoms, in similar
      patterns but to different degrees. Specifically, changes in fatigue depended more
      on the valence dimension, whereas changes in depressive symptoms depended on both
      the valence and arousal dimensions. Theoretical and practical implications of the
      current findings are discussed and suggestions for interventions to alleviate
      fatigue and depressive symptoms in cancer patients are proposed.

PMID- 17000349
TI  - The prevalence of concern about weight loss and change in eating habits in people
      with advanced cancer.
AB  - Weight loss and anorexia are commonly reported symptoms in people with advanced
      cancer. Little is known about patient experience of these phenomena, in
      particular whether they find them of concern. In this study, the prevalence of
      weight loss and eating-related concern was evaluated in patients with advanced
      cancer receiving specialist palliative homecare. The survey was a component of a
      larger study exploring the potential for helping patients and their families live
      with weight loss and change in eating habits. Patients were under the care of two
      specialist palliative homecare teams in the south of England in 2003. The
      questionnaire was distributed to the total eligible caseload of 233 patients with
      advanced cancer. The response rate was 85%. More than three-quarters of the 199
      patients who returned the questionnaires reported weight loss (79%) and/or eating
      less (76%). Excluding the 32 patients (16%) who had sought help from a family
      member or friend to complete the questionnaires, more than half (52%) reported
      concern about weight loss and/or eating. Concern about weight loss or eating was
      found irrespective of proximity to death. Weight loss and eating-related concerns
      are commonly experienced by people with advanced cancer receiving palliative
      homecare. Further work is needed to establish if concerns are amenable to
      interventions that translate into meaningful outcomes for patients and their
      families.

PMID- 17000350
TI  - Personality, neuroticism, and coping towards the end of life.
AB  - The influence of personality characteristics on how patients cope with various
      challenges at the end of life has not been extensively studied. In order to
      examine the association between end-of-life experience and neuroticism (defined
      within the personality literature as a trait tendency to experience psychological
      distress), a measure of neuroticism was administered to a cohort of dying cancer
      patients. Various other measures of physical, psychological, and existential
      distress were also measured to explore their possible connection to patient
      personality style. The personality characteristic neuroticism demonstrated a
      significant relationship with several end-of-life sources of distress, including
      depression, anxiety, sense of dignity, quality of life (rating and satisfaction),
      hopelessness, concentration, and outlook on the future. Neuroticism appears to
      have a significant association with the dying experience. This association is
      expressed across the psychological, existential and, to a lesser extent, physical
      and social domains of end-of-life distress. This may help clinicians identify
      vulnerable individuals who are most likely to have poorer adjustments and may
      benefit from earlier targeted interventional approaches. Exploring the
      relationship between various facets of personality and end-of-life distress, and
      mapping this information against optimal therapeutic responses, remains the
      challenge for future research broaching this intriguing and largely ignored area
      of palliative care.

PMID- 17000351
TI  - The addiction behaviors checklist: validation of a new clinician-based measure of
      inappropriate opioid use in chronic pain.
AB  - This study introduces the Addiction Behaviors Checklist (ABC), which is a brief
      (20-item) instrument designed to track behaviors characteristic of addiction
      related to prescription opioid medications in chronic pain populations. Items are
      focused on observable behaviors noted both during and between clinic visits. One
      hundred thirty-six consecutive veterans in a multidisciplinary Veterans Affairs
      Chronic Pain Clinic who were receiving long-term opioid medication treatment were
      included in this study. This study represents one of the first to follow a sample
      of chronic pain patients on opioid therapy over time, using a structured
      assessment tool to evaluate and track behaviors suggestive of addiction.
      Interrater reliability and concurrent validity data are presented, as well as a
      cut-off score for use in determining inappropriate medication use. The
      psychometric findings support the ABC as a viable assessment tool that can
      increase a provider's confidence in determinations of appropriate vs.
      inappropriate opioid use.

PMID- 17000352
TI  - Management of phantom pain with a textile, electromagnetically-acting stump
      liner: a randomized, double-blind, crossover study.
AB  - The treatment of phantom pain is frequently dissatisfying. We wanted to find out
      whether an electromagnetically shielding stump stocking interwoven with metal
      (medipro(R)Liner RELAX [medi Bayreuth, Bayreuth, Germany]) could have a positive
      effect on phantom pain. A double-blind, randomized, crossover trial in a total of
      30 leg amputees compared the experimental (=verum) silicon liner (VL) fitted to
      the amputation stump with a dummy (=placebo) liner (PL). Each liner was worn for
      two weeks after a two-week baseline period. Daily documentation focused on
      phantom pain, quality of sleep and improvement of well-being. Twenty-seven of 30
      patients completed the 6-week study, and 22 documentations proved valid. On a 0
      10 numeric rating scale (NRS), the median pain intensity before treatment was 4,
      and the median of maximum pain was 6. VL versus PL reduced pain significantly
      more often (P=0.008), the odds ratio being 5.95. The degree of pain reduction was
      likewise highly significant (<0.001). Wilcoxon's matched-pairs signed-rank test
      for the medians of daily maximum pain showed a significant reduction for both PL
      (P < 0.001) and VL (P <0.001) as compared to baseline, with VL being highly
      superior again (P < 0.001) versus PL. The experimental device also led to
      significant amelioration of general well-being (P = 0.037) with an odds ratio of
      3.85, and an improvement in the quality of sleep, which was not significantly
      different than PL (P = 0.223). In this study, the influence of a silicon liner
      with electromagnetically protecting properties on phantom pain was highly
      significant. The mechanisms underlying this effect are unclear. Possibilities
      include reduction of ectopic neuroma activity, shielding from possible
      electromagnetic weather impulses (sferics), or analgesic effects of changes in
      the electromagnetic field. PET or fMRI examination with or without a shielding
      silicon liner might help to elucidate this observation further.

PMID- 17000353
TI  - A survey of perceptions with pain management in Spanish inpatients.
AB  - The aim of this study was to document the satisfaction with pain management in a
      Spanish inpatient population and its relationship with pain ratings. Two hundred
      fifty inpatients of four departments were interviewed: Surgery, Orthopedics,
      Gynecology, and Internal Medicine. A 32-item questionnaire was used, and the main
      variables evaluated were pain severity, dissatisfaction with pain management and
      caregivers, and patient expectations regarding pain relief. Relationships among
      the variables were analyzed by means of Spearman's correlation between item
      scores and regression analysis. Median satisfaction scores were consistent with
      "very satisfied." Mean (SD) worst pain during the past 24 hours was 68.8 (27.5)
      on a 100 mm visual analogue scale. "Dissatisfaction with Pain Management"
      correlated positively with "Dissatisfaction with Medical Staff" (0.42), and
      inversely with "Pain Now" (-0.41) and "Expected Pain Relief" (-0.38). Regression
      analysis showed that "Dissatisfaction with Pain Management" was dependent on
      "Pain Now," "Least Pain," and "Dissatisfaction with Medical Staff," with
      statistically significant beta weight values of 0.277, 0.197, and 0.280,
      respectively. The study shows that patients were highly satisfied with pain
      management, even when they were in pain. Moreover, it establishes that patient
      dissatisfaction with treatment was highly related to the satisfaction with
      caregivers and pain intensity.

PMID- 17000354
TI  - Nociceptin levels in the cerebrospinal fluid of chronic pain patients with or
      without intrathecal administration of morphine.
AB  - The neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the
      opioid-like receptor ORL-1 and is thought to be involved in pain transmission and
      modulation. Human studies have not yet defined its role in pain patients. The
      aims of this study were 1) to verify the presence of N/OFQ in the cerebrospinal
      fluid (CSF) of human controls and patients with chronic noncancer pain, including
      those treated with intrathecally administered morphine, and 2) to determine
      whether pain or treatment with long-term intrathecal morphine influences its
      levels. The CSF of 27 patients (nine controls and 18 with chronic noncancer pain,
      of whom 12 were treated chronically with intrathecally administered morphine and
      six were opioid naive) was analyzed, blindly, with radioimmunoassay methods.
      N/OFQ was detected in all patients. Mean CSF concentrations were lowest in the
      morphine-treated group and highest in the untreated chronic pain patients
      (12.06+/-1.19 and 57.41+/-10.06 fmol/ml, respectively), and the difference
      between the morphine-treated group and controls was statistically significant
      (44.72+/-13.56 fmol/ml, P<0.05). The presence of N/OFQ peptide in human CSF may
      correlate with biological activities that are influenced by different pain states
      and long-term intrathecal-morphine treatment. Further studies should verify
      whether the determination of this peptide CSF level may provide information on
      opioid treatment efficacy and on the presence of opioid tolerance.

PMID- 17000355
TI  - Methodological challenges in measuring quality care at the end of life in the
      long-term care environment.
AB  - Understanding what constitutes quality end-of-life care from the perspective of
      the patient, their family, and health care professionals has been a priority for
      many researchers in the past few decades. Literature in this area has helped
      describe many of the barriers to measuring the quality of care in various
      environments, such as the hospital, hospice, and home. However, much of the work
      to date in defining the domains of quality care at the end of life has not been
      conducted within the long-term care environment. This environment is expected to
      provide care to an increasing number of dying persons with the concurrent aging
      of the population in many Western countries and demand for more formal services.
      In this review, the methodological issues involved in measuring quality care at
      the end of life are examined, with specific attention given to the challenges
      encountered in the long-term care environment.

PMID- 17000358
TI  - Prognostic value of myocardial perfusion contrast echocardiography in patients
      with suggested or known ischemic heart disease.
AB  - OBJECTIVE: We sought to determine the prognostic value of myocardial contrast
      echocardiography (MCE) in patients with known or suggested coronary artery
      disease compared with technetium-99m sestamibi single photon emission computed
      tomography (SPECT)-myocardial perfusion imaging (MPI). BACKGROUND: The prognostic
      value of SPECT-MPI is well established for patients with coronary artery disease.
      It is less well defined by MCE. METHODS: In all, 51 consecutive patients with
      suggested coronary artery disease prospectively underwent MCE and SPECT-MPI at
      baseline and after dipyridamole infusion. MCE and SPECT-MPI were independently
      analyzed for myocardial perfusion. Cardiac events during the follow-up period
      were determined, and event-free survival was calculated for MCE and SPECT-MPI
      techniques separately. RESULTS: MCE (log rank P < .005) and SPECT-MPI (log rank P
      < .05) demonstrated equivalent event-free survival. The negative predictive value
      for events for both MCE and SPECT-MPI was 100%. CONCLUSION: MCE accurately
      classifies patients at risk for cardiac events and provides prognostic
      information comparable with validated SPECT-MPI techniques.

PMID- 17000359
TI  - Prediction of transmural extent of infarction with contrast echocardiographically
      derived index of myocardial blood flow and myocardial blood volume fraction:
      comparison with contrast-enhanced magnetic resonance imaging.
AB  - BACKGROUND: We sought to determine the accuracy of myocardial contrast
      echocardiography (MCE)-derived index of myocardial blood flow and myocardial
      blood volume fraction (MBVF) in predicting transmural extent of infarction and
      wall-motion recovery. METHODS: Low and high mechanical index MCE and contrast
      enhanced magnetic resonance imaging were performed 5 to 7 days after successful
      percutaneous revascularization in 30 patients with acute myocardial infarction
      and regional wall-motion change was assessed 3 months later. The index of
      myocardial blood flow was calculated as A x beta (dB/s) using the equation y = A
      (1 - e(-beta t)), which fits the replenishment curve of low mechanical index MCE.
      The MBVF (mL/100 g myocardium) was calculated as 100 x 10(relative contrast
      intensity [CI]/10), using the relative CI by subtracting the cavity CI from the
      adjacent transmural CI using high mechanical index MCE. The contrast-enhanced
      magnetic resonance imaging-derived transmural extent of delayed hyperenhancement
      (DE) in 16 segments were measured and compared with corresponding MCE data.
      RESULTS: Among 480 segments, 382 measurable segments were subdivided into 5
      groups as follows: no DE, 1% to 25% DE, 26% to 50% DE, 51% to 75% DE, and 76% to
      100% DE. An increment of the extent of DE was significantly related to a
      decrement of A x beta (P < .001) and MBVF (P < .001). The optimal cut-off MBVF
      for predicting greater than 50% DE was 1.92 mL (sensitivity 82%, specificity 73%,
      P < .01), and persistently dysfunctional motion was 1.81 mL (sensitivity 74%,
      specificity 75%, P < .01). CONCLUSION: The MCE-derived A x beta and MBVF can be
      effective predictors of transmural extent of infarction and wall-motion recovery
      in the reperfused acute myocardial infarction.

PMID- 17000360
TI  - Transthoracic coronary flow velocity reserve assessment: comparison between
      adenosine and dobutamine.
AB  - OBJECTIVE: We sought to compare coronary flow velocity reserve (CFVR) with
      adenosine and dobutamine in patients scheduled for noninvasive evaluation of
      coronary artery disease. BACKGROUND: Assessment of CFVR in the distal part of the
      left anterior descending coronary artery (LAD) by Doppler transthoracic
      echocardiography (TTE) is usually performed with adenosine in various settings.
      CFVR can also be determined during dobutamine stress echocardiography (DSE), but
      it has not been established whether TTE CFVR with dobutamine is equivalent to
      CFVR with adenosine. METHODS: In all, 47 consecutive stable patients in sinus
      rhythm (28 men, 64 +/- 12 years, left ventricular ejection fraction 55 +/- 5%)
      were prospectively studied. Coronary flow velocity was measured in the distal
      part of the LAD by TTE, at rest and during continuous infusion of 0.14 mg/kg/min
      of adenosine over 2 minutes, and during DSE performed immediately after the
      adenosine test, using a multifrequency transducer, on a modified parasternal
      view. CFVR with adenosine was calculated as hyperemic to basal peak flow
      velocity. CFVR with DSE was obtained by calculating peak diastolic flow velocity
      divided by baseline diastolic flow velocity. RESULTS: Adequate recording of CFVR
      with adenosine and dobutamine was possible in 43 (91%) and 41 (87%) patients,
      respectively. CFVR was 2.5 +/- 0.7 with adenosine compared with 2.4 +/- 0.7 with
      dobutamine (P = .7). A good linear correlation was observed between the two tests
      (r = 0.81, P < .0001). In patients with dobutamine-induced wall-motion
      abnormalities in the LAD territory (n = 8), CFVR was similar during dobutamine
      and adenosine infusion (1.6 +/- 0.3 vs 1.5 +/- 0.2, respectively, P = .7).
      Coronary angiography was available in 12 patients (LAD stenosis: 55 +/- 10%
      quantitative coronary angiography, with a range from 40%-75%). The correlation
      between CFVR values was also good in this subgroup of patients (r = 0.87, P <
      .0001). CONCLUSION: TTE CFVR with dobutamine is comparable to CFVR with adenosine
      in patients with a wide range of LAD diseases. Dobutamine could be a good
      alternative to adenosine for TTE CFVR assessment, particularly in patients with a
      contraindication to adenosine or scheduled for DSE.

PMID- 17000361
TI  - Prognostic value of mitral regurgitation assessment during exercise
      echocardiography in patients with known or suspected coronary artery disease.
AB  - BACKGROUND: Although mitral regurgitation (MR) may be assessed during exercise
      echocardiography (EE) there are no data regarding its value for predicting
      outcome in large series of patients. We sought to determine whether the
      predictive value of EE is maintained over clinical variables and resting
      echocardiography when the latter included information on MR, and to verify
      whether postexercise MR may improve the value of EE for predicting outcome.
      METHODS: In all, 1916 patients (mean age +/- 1SD = 62 +/- 11 years; mean left
      ventricular ejection fraction +/- 1SD = 56 +/- 11) referred for EE were followed
      up for 1.9 +/- 1.4 years. RESULTS: There were 87 cardiac events before
      revascularization: 67 events occurred in 948 patients with abnormal EE and 20
      events occurred in 968 patients with normal EE (P < .0001), whereas there were 24
      events in the 218 patients with moderate or higher resting MR and 63 events in
      the 1698 patients with no or mild MR (P < .0001). Previous myocardial infarction,
      resting MR, peak double product, and peak left ventricular ejection fraction were
      independently associated to hard events (chi2 model = 144, P < .0001). The same
      variables were associated to cardiac death (chi2 model = 141, P < .0001).
      Predictors of cardiac events in patients with abnormal EE were resting MR,
      resting wall-motion score index, metabolic equivalents, peak double product, and
      MR worsening (incremental P value of MR worsening = .03). Predictors of cardiac
      death were resting MR, peak double product, peak left ventricular ejection
      fraction, and MR worsening (incremental P value of MR worsening = .03).
      CONCLUSIONS: EE maintains its higher prognostic value over resting
      echocardiography even when the latter incorporates information on resting MR. MR
      worsening provides significant incremental prognostic information in patients
      with abnormal EE.

PMID- 17000362
TI  - Acute improvement in myocardial function assessed by myocardial strain and strain
      rate after aortic valve replacement for aortic stenosis.
AB  - OBJECTIVES: We investigated whether Doppler tissue imaging (tissue velocity,
      strain, and strain rate) could be useful to detect subtle left ventricular (LV)
      dysfunction in patients with aortic stenosis and changes in regional myocardial
      function after aortic valve replacement (AVR). METHODS: We studied 34 patients
      (age 69.2 +/- 10.4 years) with severe aortic stenosis, 21 of whom underwent AVR.
      Tissue velocity, systolic strain, strain rate, time to peak strain, and time to
      peak systolic and diastolic strain rates of basal and midsegments were measured
      in the apical 4-, 3-, and 2-chamber views before and 2 weeks after AVR. RESULTS:
      Strain and systolic strain rate showed the best correlation with LV ejection
      fraction (r = 0.80 and r = 0.70, respectively, both P < .0001). Early and late
      diastolic strain rates showed significant correlations with LV mass index (r =
      0.45, P < .01; and r = 0.64, P < .0001, respectively) and time to peak strain, to
      peak systolic strain rate, and to peak early diastolic strain rate with aortic
      pressure gradient (r = 0.45, P < .01; r = 0.44, P < .01; and r = 0.56, P < .001,
      respectively) before AVR. Although LV mass index and LV systolic function did not
      change significantly after 2 weeks (LV mass index, 137 +/- 54 vs 125 +/- 36 g/m2;
      LV ejection fraction, 60 vs 58%, both P = not significant), peak strain and
      strain rates increased (P < .001) and time to peak strain and strain rate
      shortened after AVR (P < .001). Tissue velocities did not change significantly
      after AVR. CONCLUSIONS: Strain and strain rate parameters seemed to relate to LV
      function and aortic stenosis severity. Further, they seemed to be superior to
      tissue velocity and conventional echocardiography in detecting subtle changes in
      myocardial function after AVR before LV mass and LV function showed improvement.

PMID- 17000363
TI  - Hemodynamic change in transmitral gradient during Valsalva maneuver and its
      relation with left atrial function, functional capacity, and pulmonary artery
      pressure in patients with mitral stenosis in sinus rhythm.
AB  - BACKGROUND: The hemodynamic factors contributing to the clinical symptomatology
      in patients with mitral stenosis (MS) have been under investigation. The
      objective of this study was to evaluate the use of the Valsalva maneuver in
      patients with MS and whether there is an association between the degree of the
      hemodynamic changes in transmitral gradient (TG) in response to Valsalva maneuver
      and functional status, systolic pulmonary artery pressure, and left atrial
      function in patients with MS in sinus rhythm. METHODS: The study prospectively
      evaluated 42 patients (37 female, mean age 40 +/- 10 years) with a diagnosis of
      pure MS in sinus rhythm. Patients were divided into 3 groups according to their
      New York Heart Association (NYHA) functional class. In all, 12 patients were in
      NYHA functional class I, 17 patients in class II, and 13 patients in class III.
      TG, including the mitral peak, mean, and late filling gradients, were calculated
      by the modified Bernoulli equation at rest and during the strain phase of
      Valsalva maneuver. The percentage changes in all TG in response to Valsalva were
      calculated. Traditional echocardiographic parameters for atrial function were
      also measured. RESULTS: We found that, in patients who were more symptomatic
      according to NYHA classification, a reduction in TG in response to Valsalva
      maneuver was blunted and associated with higher systolic pulmonary artery
      pressure compared with those who were asymptomatic or had mild symptoms. Patients
      in NYHA class III decreased mitral mean pressure gradient by only 13.5%,
      significantly less (P < .001) than those in classes I (53.9%) and II (41.7%).
      However, despite the fact that left atrial ejection fraction was low in all
      patients, it was not associated with functional status in patients with MS.
      CONCLUSION: This study, for the first time, suggests that echocardiographically
      determined changes in TG in response to the Valsalva maneuver may provide an
      objective, noninvasive means of evaluating patients with MS.

PMID- 17000364
TI  - Gestational diabetes: a condition of early diastolic abnormalities in young
      women.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is not merely a temporary
      condition, but a harbinger of type 2 diabetes mellitus, hypertension, and
      atherosclerotic disease. We examined the effect of GDM on cardiac diastolic
      function. METHODS: Diastolic function was evaluated by serial Doppler
      echocardiography with pulsed tissue Doppler imaging in 13 patients with GDM and
      13 healthy pregnant women (control group) during the third trimester of pregnancy
      and after 8 weeks postpartum. Diagnostic criteria for GDM were those as
      recommended by the American Diabetes Association. Exclusion criteria were any
      disease or condition that could interfere with diastolic function. Measurements
      at both times in each group were compared by paired t tests and changes of
      patients with diabetes were compared with those in control patients by unpaired t
      tests. RESULTS: There were no differences in age, left ventricular mass, or
      systolic function between groups. The Doppler parameters that showed significant
      difference between groups were higher atrial contraction wave (A wave) (P = .008)
      and lower rapid filling wave (E)/A ratio (P = .006) in diabetic group, on both
      occasions. Tissue Doppler parameters showed a significant decrease in Em (P =
      .002) and early mitral annulus velocity (Em)/late mitral annulus velocity (Am) (P
      = .008) in diabetic group on both occasions, and the Am wave remained increased
      only in the diabetic group at postpartum. CONCLUSIONS: Patients with GDM showed a
      different diastolic function profile, suggesting a mild degree of diastolic
      abnormality. The persistence of some abnormalities postpartum corroborates our
      hypothesis of an early cardiovascular involvement in this group, enhancing the
      need of a close cardiovascular follow-up of these patients.

PMID- 17000365
TI  - QRS duration alone misses cardiac dyssynchrony in a substantial proportion of
      patients with chronic heart failure.
AB  - BACKGROUND: The primary determinate for the indication of cardiac
      resynchronization therapy in symptomatic chronic heart failure currently is a
      prolonged QRS duration. This is based on the premise that a prolonged QRS
      duration is a marker of left ventricular (LV) dyssynchrony. Tissue
      synchronization imaging (TSI) is an emerging technology that uses tissue Doppler
      velocities to determine the time to peak velocity of regions of the ventricular
      myocardium. OBJECTIVES: Our objectives were to determine the prevalence of
      dyssynchrony in a cardiomyopathic population referred for echocardiography
      irrespective of QRS duration, to validate the novel technique of TSI in
      evaluation of mechanical LV dyssynchrony and to determine the accuracy of QRS
      duration in predicting significant LV dyssynchrony. METHODS: A total of 100
      patients with significant LV dysfunction (Simpson's ejection fraction < or = 35%)
      referred for echocardiography underwent TSI. Dyssynchrony was defined as a
      difference in time to peak contraction of greater than 105 milliseconds between
      opposing ventricular segments. RESULTS: Overall, 61 patients (61%) demonstrated
      significant dyssynchrony, whereas 52% had a QRS duration of greater than 120
      milliseconds. Among those with a prolonged QRS duration, significant dyssynchrony
      was evident in 30 (58%). However, dyssynchrony was also common among those with a
      narrow QRS duration (<120 milliseconds) (31 patients [65%]). Of the 61 patients
      with dyssynchrony, 31 (51%) would have been missed if QRS criteria were used
      alone. CONCLUSIONS: A substantial proportion of patients have dyssynchrony by
      TSI, but do not have a prolonged QRS duration. These patients may benefit from
      cardiac resynchronization therapy but on traditional criteria would be excluded
      from the therapy. Expanding the criteria for cardiac resynchronization therapy to
      include echocardiographic parameters may extend the benefit of this technology to
      a greater population in need.

PMID- 17000366
TI  - Quantitative measures of right ventricular dysfunction by echocardiography in the
      diagnosis of acute nonmassive pulmonary embolism.
AB  - BACKGROUND: Transthoracic echocardiography (TTE) is used in the risk assessment
      of patients with pulmonary embolism (PE), but the incremental diagnostic
      information from quantitative measures of right ventricular (RV) size, pressure,
      and function by TTE has yet to be fully evaluated. METHODS: In 300 consecutive
      patients with suspected first nonmassive PE, TTE and ventilation/perfusion
      scintigraphy were performed. RESULTS: Among measures of RV anatomy, RV pressure
      estimates, and estimates of global and regional RV function with significant
      diagnostic information in a logistic regression analysis, the acceleration time
      of RV outflow less than 89 milliseconds, the ratio of RV to left ventricular
      diameter greater than 0.78, RV outflow tract fractional shortening less than 35%,
      and signs of RV strain on electrocardiogram had independent, incremental
      diagnostic information (area under the receiver operating characteristics curve =
      0.81). If D-dimer greater than 4.1 mmol/L was included, the area under the curve
      increased to 0.88. The negative and positive predictive values if any 2 of 3
      factors in the final model were present were 88% and 70%, respectively.
      CONCLUSION: TTE is able to identify differential diagnoses and enhance pretest
      probability of PE significantly. TTE could therefore be considered as an integral
      part of the initial diagnostic workup of patients suspected of PE, especially if
      definitive diagnostic imaging has limited availability.

PMID- 17000367
TI  - Sequence of echocardiographic changes during development of right ventricular
      failure in rat.
AB  - BACKGROUND: The temporal relations between the onset of echocardiographic changes
      and clinical diagnosis of right ventricular (RV) failure are unresolved. We have
      characterized such relations in a rat monocrotaline (MCT) model of RV failure.
      METHODS: Eight-week-old male Wistar rats were injected with MCT (60 mg/kg) or
      vehicle and underwent serial echocardiography. RV free-wall thickness (RVWT),
      pulmonary artery acceleration time normalized to cycle length (PAAT/CL), RV end
      diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion
      (TAPSE) were measured. RESULTS: Significant differences in echocardiographic
      parameters between MCT-treated and control rats were found as early as 14 days
      before RV failure for RVWT, 10 days for PAAT/CL, and 7 days for RVEDD and TAPSE.
      The time intervals between the onset of changes in RVWT, PAAT/CL, RVEDD, and
      TAPSE and diagnosis of RV failure were 11.3 +/- 0.8, 10.9 +/- 0.7, 6.5 +/- 0.5,
      and 5.4 +/- 0.7 days, respectively. The sequence of echocardiographic changes was
      consistent in all animals during development of RV failure. CONCLUSIONS:
      Pulmonary hypertension (assessed by PAAT/CL) and RV free-wall thickening
      (characterized by RVWT) precede RV dilation and RV systolic dysfunction (measured
      by RVEDD and TAPSE, respectively). Echocardiographic analysis permits accurate
      determination of the stage of disease development in MCT-induced RV failure.

PMID- 17000368
TI  - Myocardial adaptation to short-term high-intensity exercise in highly trained
      athletes.
AB  - We aimed to clarify the myocardial adaptation to short-term high-intensity
      exercise among trained athletes. We screened 17 participants in the 2004 World
      Indoor Rowing Championships before and after a 2000-m sprint. Echocardiography
      included standard measurements and tissue Doppler-derived strain (epsilon),
      strain rate, and 2-dimensionally derived speckle-tracking imaging for left
      ventricular (LV) torsion. LV volumes and ejection fraction were unchanged after
      exercise. There was a reduction in early and an increase in late diastolic
      filling velocities and a decrease in the flow propagation velocity. Annular
      systolic velocities, slope of the systolic acceleration, septal and lateral
      epsilon, and speckle tracking-derived torsion were increased. The increased LV
      torsion was a result of increased basal and apical rotation. Right ventricular
      apical epsilon decreased. In conclusion, maximal intensity short-duration
      exercise was associated with attenuation of LV diastolic function, augmentation
      of LV systolic function, and a reduction in apical right ventricular
      contractility.

PMID- 17000369
TI  - Use of hand-held ultrasound by a nonsonographer clinician to measure carotid
      intima-media thickness.
AB  - OBJECTIVE: We sought to evaluate the accuracy of carotid intima-media thickness
      (CIMT) measurements by a nonsonographer clinician using hand-held ultrasound
      (HHU). BACKGROUND: Use of a HHU for point-of-care CIMT measurement has not been
      tested previously. METHODS: Participants underwent reference ultrasound and HHU
      studies. HHU validity was tested by an expert sonographer. Nonsonographer
      clinician accuracy using the HHU was tested against the expert sonographer. CIMT
      bioequivalence was tested with .5 pixel limits. RESULTS: The 75 participants were
      (mean [SD]) 55 [7] years old. CIMT values were bioequivalent (0.714 [0.029] vs
      0.685 [0.029] mm, phase I; 0.697 [0.015] vs 0.687 [0.015] mm, phase II; P(two 1
      sided t test) < .05). Agreement was 80% for CIMT classifications (intraclass
      correlation coefficient = 0.451, P < .001) and 90% for plaque presence
      (intraclass correlation coefficient = 0.797, P < .001). CONCLUSIONS: CIMT
      measured by HHU was bioequivalent to a reference ultrasound system, when used by
      an expert sonographer or nonsonographer clinician. Clinical classifications by
      CIMT quartile and plaque presence were similar. HHU may be suitable for office
      based atherosclerosis screening.

PMID- 17000370
TI  - Floating heart metastasis.
AB  - Renal-cell carcinoma accounts for 2 percent of all cancers and a third of the
      patients who undergo resection of localized disease will have a recurrence. We
      report a case of a 58-year-old man with a right atrial mass protruding into right
      ventricle arising from the inferior vena cava, found by echocardiography, which
      was subsequently proved to be a recurrence of renal-cell carcinoma 25 years after
      radical left nephrectomy. This pattern of late recurrence is rare and suggests
      that this tumor's aggressive nature contributed to the degree of heart invasion
      and the patient's rapid death.

PMID- 17000371
TI  - Left ventricular diverticulum with contractile function in an unusual site.
AB  - The diverticulum of the left ventricular cavity is a rare congenital
      malformation. Various imaging modalities such as echocardiography, computed
      tomography, magnetic resonance imaging, and left ventriculography might be used
      for anatomic and functional properties of this abnormality. This report presents
      the case of a 48-year-old man with a contractile left ventricular diverticulum in
      the left ventricular outflow tract area and the evaluation with real-time
      multiplane and 3-dimensional transthoracic echocardiography.

PMID- 17000372
TI  - Extreme redundancy of the valve of the fossa ovalis with right heart hypoplasia
      in a neonate with trisomy 18.
AB  - Infants with trisomy 18 often have important cardiovascular malformations. We
      describe an infant with trisomy 18 who had extreme redundancy of the flap valve
      of the fossa ovalis along with right heart hypoplasia.

PMID- 17000373
TI  - Right ventricular metastasis of uterine squamous cell carcinoma.
AB  - This imaging case report demonstrates abnormal right ventricular masses of
      primarily unknown origin. The woman was admitted because of right heart failure
      symptoms. Echocardiography showed the masses exclusively related to the right
      ventricular endomyocardium and extending through the entire length and breadth of
      the ventricle. Systolic function was normal without evidence of outflow tract
      obstruction. The patient died in 3 days because of multisystem failure. Autopsy
      findings confirmed metastasis on the right ventricle and histopathology
      demonstrated the infrequent finding of metastasis from uterine squamous cell
      carcinoma, which had been operated on 5 years before.

PMID- 17000374
TI  - Pseudodyskinesis--a novel mechanism for abnormal motion of the heart's
      diaphragmatic wall.
AB  - We report a case of pseudodyskinesis, where there is dyssynchronous contraction
      of the heart's diaphragmatic wall despite normal wall thickening. This finding
      has previously been reported in a small group of patients with liver disease, and
      has been attributed to elevation of the diaphragm as a result of hepatomegaly and
      ascites. Our case demonstrates similar findings in a patient without liver
      disease, in whom the diaphragm was elevated secondary to volume loss in the
      chest. Our case supports the assertion that diaphragmatic elevation, regardless
      of cause, is indeed responsible for this probably common echocardiographic
      finding.

PMID- 17000375
TI  - Twenty-five-year-old man with a giant left ventricular mass.
AB  - We report a rare case of a massive 7- x 3.25-cm thrombus in the left ventricle of
      a 25-year-old man. He presented with a subacute febrile illness for 1 month with
      a sudden worsening respiratory distress and chest pain. His initial evaluation in
      the emergency department diagnosed an interstitial lung process. Two-dimensional
      echocardiography demonstrated a previously undiagnosed cardiomyopathy and a
      massive left ventricular thrombus.

PMID- 17000376
TI  - Detection of heart transplant rejection in adults by echocardiographic diastolic
      indices: a systematic review of the literature.
AB  - BACKGROUND: Diastolic dysfunction is often used as a marker of allograft
      rejection in patients with cardiac transplantation. However, the strength of
      evidence to support this approach needs to be determined. METHODS: We sought to
      review and evaluate the quality of the published data about the use of diastolic
      indices (DI) to predict a rejection episode. A MEDLINE search was performed to
      identify English-language articles published from 1967 to 2005 that used DI to
      predict rejection episodes. The references of each retrieved article were scanned
      to identify additional relevant articles. Studies showing the correlation between
      echocardiography findings and biopsy results were included. Articles were
      abstracted using a standardized instrument designed by the authors. Quality was
      assessed using standardized criteria. Discrepancies were adjudicated by
      consensus. RESULTS: Nineteen studies met the inclusion criteria. Quality of
      studies varied widely. Thirteen studies explicitly stated having an independent
      blind comparison with a reference standard, 4 studies presented reproducibility
      information, no studies presented likelihood ratios, and only 11 of them provided
      sensitivity and specificity. Left ventricular diastolic indices evaluated
      included inflow Doppler early diastolic (E) wave pressure half-time (sensitivity
      23%-87%, specificity 76%-98%) and isovolumetric relaxation time (sensitivity 28%
      85%, specificity 80%-98%), as well as tissue Doppler early diastolic (E') wave
      (sensitivity 69%-76% and specificity 59%-88%) and late diastolic (A') wave
      (sensitivity 67%-82%, specificity 49%-53%). CONCLUSION: Because of inconsistent
      quality of the studies and low sensitivities, the current literature does not
      support the use of DI by echocardiography as a screening test in the prediction
      of allograft rejection in the heart transplantation population. Larger controlled
      studies incorporating newer DI such as tissue Doppler are needed.

PMID- 17000377
TI  - Response to comments on our article "Measurement of cardiac time intervals by
      Doppler tissue M-mode imaging of the anterior mitral leaflet".

PMID- 17000383
TI  - Pre-liver transplantation locoregional adjuvant therapy for hepatocellular
      carcinoma as a strategy to improve longterm survival.
AB  - BACKGROUND: Preorthotopic liver transplantation locoregional therapy (LRT) for
      hepatocellular carcinoma (HCC) reduces drop-out rates in patients awaiting
      orthotopic liver transplantation (OLT). In this study, we investigated the
      efficacy of LRT as a strategy to improve longterm survival after transplantation.
      STUDY DESIGN: A retrospective analysis of prospectively collected data identified
      100 patients with HCC who underwent OLT between 1985 and 2005. Of these, 46
      received LRT in the form of transarterial chemoembolization, radiofrequency
      ablation, percutaneous ethanol injection, or a combination of these. RESULTS: The
      1-, 3-, and 5-year survivals, regardless of LRT, were 81.3%, 66.1%, and 61.3%,
      respectively. Demographic data and waiting time for OLT were similar between LRT
      and untreated groups. Pre-OLT radiologic stage was comparable (LRT: 2.11 +/- 0.74
      versus Untreated: 2.39 +/- 0.94; p = 0.16). At the time of transplantation, the
      LRT group had notable tumor downstaging (1.50 +/- 1.34 versus 2.49 +/- 1.17; p =
      0.008). The LRT group had better 5-year survival (82.4% versus 51.8%; p = 0.01),
      but this improvement was observed in patients with HCC stages II, III, and IV
      (77.6% versus 37.4%; p = 0.016). Sixteen LRT patients, and none untreated,
      revealed complete tumor necrosis with no viable tumor cells on explant pathology
      (pT0). These patients did not experience any longterm recurrence, in contrast to
      those with similar pre-OLT tumors. CONCLUSIONS: OLT is a viable treatment option
      for primary HCC. LRT substantially downstages the primary tumor and improves
      longterm survival in patients with advanced disease. Complete tumor necrosis with
      LRT is associated with excellent longterm recurrence-free survival.

PMID- 17000384
TI  - Incisional hernia after liver transplantation.
AB  - BACKGROUND: Incisional hernia is a potential complication of orthotopic liver
      transplantation (OLT), with various options for repair. STUDY DESIGN: We
      conducted a retrospective review of a series of adult patients with incisional
      hernias after OLT to identify risk factors and to compare methods of repair.
      RESULTS: Incisional hernia repair was performed in 44 of 959 patients (4.6%) who
      underwent OLT from 1999 to 2005. Mean age at time of OLT was 53 years, and 73%
      were men. One or more complications of OLT occurred in 33 patients (75%) and
      included reoperation for bile leak or hemoperitoneum (34%), pulmonary problems
      (27%), early acute rejection (7%), and severe ascites and retransplantation (5%
      each). Incisional hernia was diagnosed at 419 days (range 62 to 1,524 days) and
      repaired at 471 days (range 109 to 1,581 days) after OLT. Presentation included
      pain or discomfort (78%) and incarceration or strangulation (5%); 17% were
      asymptomatic. Herniorrhaphy techniques included fascial repair with onlay
      polypropylene mesh reinforcement (n=25, 57%); fascial repair only (n=15, 34%); or
      inlay mesh sewn to fascial edges (n=4, 9%). Complications of repair included
      recurrence in seven patients (16%) and wound infection and seroma in one patient
      each. Recurrence occurred in five patients with primary repair and two with mesh
      techniques (33% versus 6%, p=0.04). CONCLUSIONS: Incisional hernia is a late
      complication of OLT for which male gender and early post-OLT complications are
      risk factors. Repair is safe when undertaken after acute problems have resolved
      and is best accomplished using mesh reinforcement of autologous tissue.

PMID- 17000385
TI  - Prognostic value and clinical relevance of the 6th Edition 2002 American Joint
      Committee on Cancer staging system in patients with resectable hepatocellular
      carcinoma.
AB  - BACKGROUND: A simplified American Joint Committee on Cancer (AJCC) TNM staging
      system for hepatocellular carcinoma (HCC) (the 6th edition) was proposed in 2002.
      In this study, we validated the prognostic value of the staging system in a
      patient cohort undergoing hepatic resection with longterm followup. STUDY DESIGN:
      From a prospective database, the study cohort consisted of 440 patients who
      underwent curative hepatic resection for HCC between July 1991 and January 1999.
      Median followup time was 66 months. Multivariate analysis was performed to
      identify the independent prognostic factors related to postoperative survival.
      Patients were staged according to both the 5th edition (TNM-5) and 6th edition
      (TNM-6) AJCC TNM staging criteria. RESULTS: The independent prognostic factors
      included major vascular invasion, microvascular invasion, surgical margin < 1 cm,
      indocyanine green retention rate at 15 minutes > 10%, multiple tumors, tumor
      rupture, male, and serum aspartate aminotransferase > 90 U/L. The breakdown by
      TNM-5 staging: I, 27 (6.1%); II, 108 (24.5%); III, 218 (49.5%); and IVA, 87
      (19.8%) and by TNM-6 staging: I, 120 (27.3%); II, 170 (38.6%); and III, 150
      (34.1%). When stratified according to the TNM-5 system, difference in survival
      was notable between stages II and IIIA (p < 0.001), between stages IIIA and IVA
      (p < 0.001), but not between stages I and II (p > 0.05). When stratified
      according to the TNM-6 system, difference in survival was considerable between
      stages I and II (p < 0.01), stages II and III (p < 0.001), and stages I and III
      (p < 0.001). CONCLUSIONS: Overall, the TNM-6 staging system appears to provide a
      reliable prognostic classification of HCC patients and is simpler to use than the
      TNM-5 staging system.

PMID- 17000386
TI  - Hepatectomy enables prolonged survival in select patients with isolated
      noncolorectal liver metastasis.
AB  - OBJECTIVE: This study was done to determine the benefit of undergoing liver
      resection for noncolorectal metastasis. METHODS: A single-institution
      retrospective review of all patients (n = 95) who underwent hepatic resection for
      a noncolorectal liver metastasis from 1990 to 2005 was performed. Primary
      outcomes measure was months of patient survival after liver resection. RESULTS:
      Median patient age was 58 years (range 19 to 83 years). There were 37 men (38.9%)
      and 58 women (61.1%). The 30-day postoperative mortality rate was 2.1%, and
      postoperative complications developed in 15.8% of patients. Mean hospital stay
      was 7 days (range 4 to 25 days). Median time of survival from date of liver
      resection was 36 months, and 5-year survival rate was 34.9%. Primary tumor sites
      were identified as foregut or gastrointestinal in 16.8% and nongastrointestinal
      in 83.2%. Patients with a nonforegut primary tumor had a median survival time
      twice as long as those with foregut primaries (49 months versus 20 months, p <
      0.001). Multiple liver metastases were an independent prognostic factor for worse
      outcomes with a hazard ratio of 3.3 (p = 0.007). No treatment-dependent variables
      (initial treatment modality, extent of liver resection, margins, complications)
      were found on multivariable analysis to be important prognostic factors.
      CONCLUSIONS: In select patients with any of a variety of malignancies metastatic
      to the liver, prolonged survival can result from liver resection, especially in
      those with a single, resectable tumor from a nongastrointestinal primary site.

PMID- 17000387
TI  - Cost effectiveness of laparoscopic versus open mesh hernia operation: results of
      a Department of Veterans Affairs randomized clinical trial.
AB  - BACKGROUND: Evidence comparing laparoscopic versus open hernia repair has varied
      with time and with changes in techniques used. Cost effectiveness is an important
      consideration when evidence for predominance of one surgical technique is
      lacking. Current cost estimates of hernia repair are not available. STUDY DESIGN:
      This study is a cost effectiveness analysis within a randomized controlled trial
      comparing open (OPEN) versus laparoscopic (LAP) hernia repair using mesh at 14
      Department of Veterans Affairs medical centers, with 2-year followup for each
      patient. Between January 1999 and November 2001, 2,164 men with inguinal hernia
      were randomized and 1,983 had an operation; 1,395 patients (708 OPEN and 687 LAP)
      with outpatient hernia operations were included in the cost effectiveness
      analysis. Outcomes included surgical and postoperative costs, quality adjusted
      life years (QALY), and incremental cost per QALY gained or the incremental cost
      effectiveness ratio (ICER). RESULTS: Over 2 years, LAP cost an average of $638
      more than OPEN. QALYs at 2 years were similar, resulting in $45,899 per QALY
      gained (95% CI: -$669,045, $722,457). The probability that LAP is cost effective
      at the $50,000 per QALY level (slightly more costly but more effective), was 51%.
      For unilateral primary and unilateral recurrent hernia repair, the probabilities
      that LAP is cost effective at the $50,000 per QALY level were 64% and 81%,
      respectively. For bilateral hernia repair, OPEN was less costly and more
      effective. CONCLUSIONS: Overall, laparoscopic hernia repair is not cost effective
      compared with open repair. For patients with unilateral (primary or recurrent)
      hernia, laparoscopic repair is a cost effective treatment option.

PMID- 17000388
TI  - Tension-free repair versus watchful waiting for men with asymptomatic or
      minimally symptomatic inguinal hernias: a cost-effectiveness analysis.
AB  - BACKGROUND: Watchful waiting (WW) has been shown to be an acceptable option in
      men with asymptomatic or minimally symptomatic inguinal hernias when clinical and
      patient-reported outcomes are considered. Although WW is likely to be less costly
      initially when compared with tension-free repair (TFR) because of the cost of the
      operation, it is not clear whether WW remains the least costly option when longer
      term costs are considered. STUDY DESIGN: We conducted a cost-effectiveness
      analysis of a randomized controlled trial at six community and academic centers.
      We examined costs, quality-adjusted life-years (QALY), and cost-effectiveness at
      2 years of followup. Costs were assessed by applying Medicare reimbursement rates
      to patients' health-care use, which was obtained by contacting patients' health
      care providers. Quality of life was assessed using the Short Form-36 version 2
      health-related quality-of-life survey. Of the 724 men randomized, 641 were
      available for the economic analysis: 317 were randomized to TFR and 324 were
      randomized to watchful waiting. RESULTS: At 2 years, TFR patients had $1,831
      higher mean costs than WW patients (95% CI, $409-$3,044), with 0.031 higher QALY
      (95% CI, 0.001-0.058). The cost per additional QALY for TFR patients was $59,065
      (95% CI, $1,358-$322,765). The probability that TFR was cost-effective at the
      $50,000 per QALY level was 40%. CONCLUSION: At 2 years, WW was a cost-effective
      treatment option for men with minimal or no hernia symptoms.

PMID- 17000389
TI  - Locoregional recurrence after mastectomy: incidence and outcomes.
AB  - BACKGROUND: Locoregional recurrences (LRR) after mastectomy may be ominous
      events, but incidence and outcomes data are limited by heterogeneous study
      populations and the time period studied. We sought to evaluate the rate of LRR at
      a single institution in the era of multimodality therapy, identify predictors for
      isolated LRR, and examine treatment strategies and outcomes of postmastectomy
      patients with isolated LRR. STUDY DESIGN: In a prospective database, we
      identified 1,057 patients who underwent mastectomy for invasive cancer at
      Memorial Sloan-Kettering Cancer Center from 1995 to 1999. Predictive factors for
      isolated LRR were determined by univariate and multivariate analyses. Treatments
      and outcomes of patients with isolated LRR were reviewed. All patients with at
      least 2 years of followup were included. Median followup was 6 years. RESULTS:
      Overall, LRR developed in 93 of 1,057 (8.8%) patients. Thirty-four (3.2%) had
      synchronous distant metastases. Distant recurrences developed in thirty-one
      (2.9%) during the followup period (median followup, 6 years). Twenty-eight
      patients with LRR (2.6%) remained free of distant disease during the study
      period. Multivariate analysis showed age less than 35 years, lymphovascular
      invasion, and multicentricity as major predictors for isolated LRR. In the 28
      patients with isolated LRR, 24 had recurrence in the chest wall, 2 in the axilla,
      and 2 in more than 1 local site. Seventy-eight percent (22 of 28) of patients
      were rendered disease free with surgery (15 of 22), radiotherapy (13 of 22),
      chemotherapy (6 of 22), or hormones (9 of 22). CONCLUSIONS: Despite widespread
      use of adjuvant therapies during the study period, we found an LRR rate after
      mastectomy of 9%. But for patients presenting with LRR without evidence of
      distant disease, aggressive multimodality therapy is warranted because many of
      these patients can be rendered disease free.

PMID- 17000390
TI  - Comparative analysis of sentinel lymph node operation in male and female breast
      cancer patients.
AB  - BACKGROUND: Male breast cancer accounts for < 1% of breast cancers. Sentinel
      lymph node (SLN) operation is commonly used in the evaluation of female breast
      cancer patients. The purpose of this study was to determine whether SLN operation
      is as feasible and accurate in male patients compared with female patients. STUDY
      DESIGN: Between 1999 and 2005, 30 men and 2,784 women underwent SLN operation.
      Clinical and pathologic data were reviewed and statistical analysis performed.
      RESULTS: Men presented at an older age (p = 0.005) and with larger tumors than
      women (p = 0.04). The SLN was identified in 100% of men and in 98.3% of women (p
      = NS). The mean number of SLNs harvested was 3.5 in men and 3.0 in women (p =
      NS). The incidence of positive SLNs was higher in men (37.0% versus 22.3%),
      although this did not reach statistical significance (p = 0.1). In patients with
      a positive SLN there were additional non-SLNs positive in 62.5% of men, compared
      with 20.7% in women (p = 0.01). The median size of the largest lymph node
      metastasis was 10 mm in men and 3 mm in women (p = 0.03). CONCLUSIONS: SLN
      operation in clinically node-negative men is feasible and accurate. Male breast
      cancer patients present at an older age and with larger tumors than female breast
      cancer patients. Male patients have higher nodal tumor burden reflected in a
      larger size of nodal metastasis and increased risk of harboring additional
      disease in axillary lymph nodes when the SLN is positive. Intraoperative SLN
      evaluation should be considered in the surgical management of male breast cancer.

PMID- 17000391
TI  - Bacterial adherence to surgical sutures: can antibacterial-coated sutures reduce
      the risk of microbial contamination?
AB  - BACKGROUND: Surgical site infections are associated with severe morbidity and
      mortality. The role of surgical sutures in the etiology of surgical site
      infection has been the objective of discussion for decades. This study used a
      standardized in vitro microbiologic model to assess bacterial adherence and the
      antibacterial activity of a triclosan-coated polyglactin 910 (braided) suture
      against selected Gram-positive and Gram-negative clinical isolates that may
      infect surgical wounds. STUDY DESIGN: Standardized cultures (2.0 log(10) colony
      forming units/mL and 5.0 log(10) colony forming units/mL of three clinical
      strains, Staphyllococcus aureus (methicillin-resistant S aureus [MRSA]), S
      epidermidis (biofilm-positive) and Escherichia coli (extended-spectrum beta
      lactamase [ESBL]-producer) were inoculated to triclosan-coated and noncoated
      polyglactin 910 sutures to evaluate comparative adherence of bacterial isolates
      to the antibacterial coated and noncoated surgical sutures; to assess the impact
      of serum proteins (bovine serum albumin) on antibacterial activity of triclosan
      coated suture; and to document the duration of antibacterial activity of the
      triclosan-coated material. Selected suture samples were prepared for scanning
      electron microscopy to demonstrate bacterial adherence. RESULTS: Substantial (p <
      0.01) reductions in both Gram-positive and Gram-negative bacterial adherence were
      observed on triclosan-coated sutures compared with noncoated material.
      Pretreatment of surgical sutures with 20% BSA did not diminish antibacterial
      activity of the triclosan-coated braided device compared with noncoated suture (p
      < 0.01), and antibacterial activity was documented to persist for at least 96
      hours compared with controls (p < 0.01). CONCLUSIONS: The in vitro model
      demonstrated a considerable reduction (p < 0.01) in Gram-positive and Gram
      negative bacterial adherence to a triclosan-coated braided suture, which was
      associated with decreased microbial viability (p < 0.001). Because bacterial
      contamination of suture material within a surgical wound may increase the
      virulence of a surgical site infection, treating the suture with triclosan
      provides an effective strategy for reducing perioperative surgical morbidity.

PMID- 17000392
TI  - Midline abdominal wall closure: a new prophylactic mesh concept.
AB  - BACKGROUND: Despite intense research efforts, incisional hernias continue to be a
      problem in patients who undergo laparotomy. This study was designed to reinforce
      the midline laparotomy closure by including a new prosthetic design between the
      edges of the surgical wound. STUDY DESIGN: A midline incision was made in New
      Zealand white rabbits and closed by inserting a polypropylene strip, T-shaped in
      cross-section, between the incisional borders. The T was placed upside down such
      that the horizontal arm of the T, whose surface is coated with extra-low pore
      size expanded polytetrafluoroethylene, made contact with the visceral peritoneum.
      The mesh was secured by a mass polypropylene 3/0 running suture. Surgery outcomes
      in these animals were compared with those in which the surgical wound was closed
      by simple suture and with control, nonoperated animals. RESULTS: The T-mesh
      induced an increased amount of scar tissue at the midline, where neoformed
      recipient tissue appeared around the polypropylene mesh filaments. The expanded
      polytetrafluoroethylene lamina became appropriately mesothelialized. Compared
      with the simple suture, the T-mesh provided a significant gain in biomechanical
      strength at postoperative week 6 (43.99+/-4.17 Newtons and 56.96+/-10.94 Newtons,
      respectively, p < 0.05). At 6 months, the strength of the reinforced wound even
      surpassed, although not significantly, that of the control intact abdominal wall
      (82.25+/-7.60 Newtons versus 79.55+/-11.46 Newtons). Data were expressed as mean
      +/- standard deviation. CONCLUSIONS: The use of a nonabsorbable biomaterial for
      midline laparotomy closure significantly improves its biomechanical resistance.
      Used in high-risk patients or even prophylactically, this technique could reduce
      the incidence of incisional hernia.

PMID- 17000393
TI  - Outcomes after ruptured abdominal aortic aneurysms: the "halo effect" of trauma
      center designation.
AB  - BACKGROUND: Trauma centers have an array of services available around the clock
      that help reduce mortality in injured patients. Having such services available
      can benefit patients other than those who are injured. We set out to determine
      whether patients hospitalized with ruptured abdominal aortic aneurysms experience
      lower morbidity and mortality at regional trauma centers than at other acute care
      hospitals. STUDY DESIGN: We conducted a retrospective cohort study with the
      exposure being care at a trauma center and outcomes either mortality or organ
      failure. We evaluated all patients 40 to 84 years of age with a diagnosis of a
      ruptured abdominal aortic aneurysm who underwent operation during 2001 in 20 US
      states with organized systems of trauma care. We determined the relative risk of
      either death or organ failure at regional trauma centers compared with
      nondesignated centers. RESULTS: Of 2,450 patients hospitalized for ruptured
      abdominal aortic aneurysm, 867 (35%) hospitalizations occurred at regional trauma
      centers. At trauma centers, 41.4% of patients died before hospital discharge,
      compared with 45.2% of patients at nondesignated hospitals (odds ratio [OR],
      0.85; 95% CI, 0.71-1.02). After adjusting for payor, hospital beds, annual
      hospital admissions, annual inpatient operations, affiliation with a vascular
      surgery fellowship, and comorbid illnesses, the likelihood of death or organ
      failure was lower at trauma centers (OR, 0.72; 95% CI, 0.55-0.93). CONCLUSIONS:
      Care at regional trauma centers after operative repair of ruptured abdominal
      aortic aneurysm is associated with improved outcomes. We postulate that these
      benefits reflect the ability of both vascular and general surgeons to immediately
      mobilize resources for care of the patient requiring urgent operative
      intervention. The beneficial effects of trauma center designation might extend
      beyond caring for the critically injured.

PMID- 17000394
TI  - Incidence and management of seroma after arteriovenous graft placement.
AB  - BACKGROUND: Perigraft seromas are rare complications of insertion of PTFE
      hemodialysis grafts. They are often difficult to treat and recurrence is common.
      This study evaluates the incidence, potential etiologic variables, and management
      strategies for seromas after prosthetic arteriovenous graft (AVG) placement.
      STUDY DESIGN: A retrospective analysis of all patients undergoing AVG placement
      between August 2002 and December 2005 was performed to identify all patients
      diagnosed with seroma requiring surgical intervention. Multiple variables were
      analyzed to determine potential risk factors for seroma formation and outcomes of
      various forms of surgical management. RESULTS: In this interval, 535 AVG were
      inserted in 427 patients. Ten patients presented with a seroma and underwent
      surgical treatment. Overall incidence of seroma formation was 1.7%. There was no
      significant difference in seroma formation based on gender, age, diabetes, lower
      extremity versus upper extremity placement, or loop forearm versus straight
      forearm grafts. A statistically significant difference was found between upper
      arm (p = 0.007) and lower arm grafts (p = 0.04), with upper arm grafts more prone
      to seroma formation. Patients undergoing bypass of the seromatous segment of
      graft have not had a recurrence, compared with those who were simply evacuated
      and have had a mean patency of 402 days. CONCLUSIONS: Seroma complications after
      AVG insertion are higher in patients with upper arm grafts. To minimize this
      complication, meticulous operative technique is required. If a seroma develops,
      the graft might still be salvageable with aggressive management, including bypass
      of the involved segment.

PMID- 17000395
TI  - Femoral vessel injuries: analysis of factors predictive of outcomes.
AB  - BACKGROUND: Femoral vessel injuries are the most common vascular injuries treated
      in a Level I trauma center. No studies have identified risk factors for survival
      and complications. STUDY DESIGN: We performed a retrospective, 132-month study
      that included univariate and multivariate analyses. RESULTS: We studied 204
      patients with 298 vessel injuries: 204 were arterial, 94 were venous. Mean age
      (+/- SD) was 29+/-13 years and mean Injury Severity Score (+/- SD) was 17+/-8.
      There were 176 (86%) penetrating injuries and 28 (14%) blunt injuries. Arterial
      repairs included: reverse saphenous vein graft bypass, 108 (53%); primary repair,
      53 (26%); PTFE, 21 (10.2%); ligation, 13 (6.4%); and vein patch, 9 (4.4%). Venous
      repairs included: ligation, 49 (52%); primary repair, 41 (44%); and bypass, 4
      (4%). Fasciotomies included: calf, 56 (27%); thigh, 25 (12%); traumatic
      amputations, 6 (3%); and delayed amputations, 0. Overall survival rate was 91%
      (186 of 204), and adjusted survival was 95% (excluding emergency department
      thoracotomy deaths). There were 1 or more complications in 47 (23%), including
      wound infection, 31 (15%); venous thrombosis, 6 (3%); bleeding, 5 (2.5%); ARDS, 4
      (2%); and arterial thrombosis, 1 (0.5%). Predictors of mortality were age>45
      years, Injury Severity Score>25, common femoral artery injury, associated venous
      and abdominal injury, hypotension, hypothermia, and acidosis; coagulopathy in the
      operating room and the need for PTFE repair also predicted outcomes. Predictors
      of postoperative complications were intraoperative hypotension, arterial intimal
      injury, bony fracture, and thoracic injury. CONCLUSIONS: Although survival and
      limb salvage rates are high for femoral vessel injuries, these injuries incur
      high complication rates. Independent predictors for mortality are: Injury
      Severity Score > 25, Glasgow Coma Scale 28, presence of coagulopathy in the
      operating room, presence of two or more vascular signs, and age > 45 years.

PMID- 17000396
TI  - Role of rectosigmoidectomy and stripping of pelvic peritoneum in outcomes of
      patients with advanced ovarian cancer.
AB  - BACKGROUND: The peritoneum of the cul-de-sac is frequently affected in advanced
      ovarian cancer patients. Stripping of the pelvic peritoneum (SoP) combined with
      rectosigmoidectomy (RS) in patients with confluent tumor are safe techniques that
      can eradicate macroscopic disease. We evaluated the therapeutic value of this
      maximal surgical effort in advanced ovarian cancer. STUDY DESIGN: Data from all
      consecutive patients with stages IIIC and IV epithelial ovarian cancer, primarily
      operated on from 1994 through 1998, were collected and analyzed using the chi
      square test, Cox regression analysis, and Kaplan-Meier curves including log-rank
      test. RESULTS: Two hundred forty-four eligible patients were identified; 209
      patients had tumor involving the peritoneum of the cul-de-sac. For this subgroup,
      those who were managed with stripping of the peritoneum (SoP, n=77) or
      rectosigmoidectomy (RS, N=57) had improved 5-year overall survivals relative to
      those who were not (n=75). (SoP=37% versus RS=39% versus neither=6%; p < 0.0001).
      In the subgroup of patients with cul-de-sac involvement optimally cytoreduced, we
      noted a survival benefit for those who were managed with a maximal pelvic
      surgical effort (5-year overall survival, 38% [SoP] versus 38% [RS] versus 15%
      [neither]; p=0.02). When evaluating patients with no macroscopic residual
      disease, a survival advantage for patients managed with RS compared with SoP was
      observed (5-year overall survival, 89% (RS) versus 50% (RS); p=0.04).
      CONCLUSIONS: Surgical resection of cul-de-sac disease by SoP and RS is associated
      with improved survival in ovarian cancer patients. Tumor resection with en bloc
      RS may be preferable to allowing microscopic or infiltrative residual tumor.

PMID- 17000397
TI  - Bowel resection at the time of primary debulking for epithelial ovarian
      carcinoma: outcomes in patients treated with platinum and taxane-based
      chemotherapy.
AB  - BACKGROUND: Our goal was to determine the morbidity, disease-free survival, and
      overall survival of patients with bowel resection at primary cytoreductive
      surgery for advanced epithelial ovarian carcinoma in the era of platinum and
      taxane chemotherapy. STUDY DESIGN: We performed a retrospective study of patients
      undergoing bowel resection at the time of primary cytoreduction for advanced
      epithelial ovarian carcinoma, who subsequently received platinum and taxane
      chemotherapy, from 1996 to 2001. Data collected included demographics, stage,
      histology, debulking status, surgical morbidity, recurrence, and survival.
      Survival analysis and comparisons were performed using the Kaplan-Meier method
      and log-rank test. RESULTS: Of 48 patients (45 stage III; 3 stage IV), 25
      patients (52%) were optimally debulked to < 1 cm of residual disease; the
      remaining 23 patients had residual disease > 1 cm. Four-year disease-free
      survival in the optimally debulked group was 24% versus 12% in the suboptimally
      debulked group (p=0.009). Four-year overall survival was 81% in the optimally
      debulked group versus 54% in the suboptimally debulked group (p=0.162). Five
      patients (10%) experienced a major postoperative complication including stroke,
      small bowel obstruction, anastomotic leak, entercutaneous fistula, and pelvic
      abscess. Two perioperative deaths occurred in the suboptimally debulked group.
      CONCLUSIONS: Patients with advanced epithelial ovarian carcinoma who undergo
      bowel resection as part of optimal cytoreduction and receive platinum and taxane
      chemotherapy have improved disease-free survival and a trend toward improved
      overall survival. Bowel resection at the time of primary cytoreductive surgery is
      associated with acceptable perioperative morbidity.

PMID- 17000398
TI  - Impact of obesity in the critically ill trauma patient: a prospective study.
AB  - BACKGROUND: Obesity has risen at an epidemic rate over the past 20 years in the
      US. To our knowledge, there is an absence of data evaluating the impact of
      obesity in the critically ill trauma patient. METHODS: Prospective data were
      collected on 1,167 patients admitted to the ICU over a 2-year period. Obesity was
      defined as a body mass index (calculated as weight [kg]/height [m(2)]) of 30 or
      higher. Outcomes analyzed included infection rate, hospital and ICU length of
      stay, and mortality. Multiple logistic regression was used to evaluate outcomes
      between obese and nonobese patients for infection (infection versus noninfection)
      and mortality (deceased versus not deceased). Continuous outcomes such as
      hospital and ICU lengths of stay were evaluated using multiple linear regression
      analyses. RESULTS: Sixty-two of 1,167 (5.3%) patients were obese. The majority
      (71%) of injuries in the study cohort were blunt. Although the majority of
      patients were men (76%), women (10% versus 4%) were more likely to be obese (p <
      0.001). Obese patients had a more than twofold increase in risk of acquiring a
      bloodstream, urinary tract, or respiratory infection, or being admitted to the
      ICU (p < 0.001), after statistically controlling for age and Injury Severity
      Score. When controlling for diabetes, gender, obesity, age, COPD, and Injury
      Severity Score, obese patients were 7.1 times (95% CI, 2.06-8.9) more likely to
      die in the hospital. CONCLUSIONS: Obesity is associated with a substantial
      increase in morbidity and mortality in the critically ill trauma patient. Future
      studies are warranted in both the prevention of infection and intensive care
      management of the obese trauma patient.

PMID- 17000399
TI  - Obesity increases risk of organ failure after severe trauma.
AB  - BACKGROUND: Obesity is an independent risk factor for a variety of diseases,
      including postinjury morbidity and mortality. Obesity is associated with a
      proinflammatory state that could affect the postinjury inflammatory response and
      increase risk of organ dysfunction. The purpose of this study was to determine
      the relationship between obesity and postinjury multiple organ failure (MOF).
      STUDY DESIGN: A prospective observational study of patients at risk for
      postinjury MOF. Inclusion criteria were age older than 15 years, Injury Severity
      Score > 15, ICU admission within 24 hours of injury, and survival longer than 48
      hours after injury. Isolated head injuries were excluded. Organ dysfunction was
      assessed using the Denver multiple organ failure score. RESULTS: Data were
      collected on 716 severely injured patients, 70% were men and 83% were victims of
      blunt trauma. There was no relationship between body mass index and injury
      severity or the amount of blood transfused within 12 hours of injury. Postinjury
      MOF was observed in 123 of 564 (22%) nonobese patients and 56 of 152 (37%) obese
      patients. Obesity was independently associated with MOF (odds ratio, 1.8; 95% CI,
      1.2-2.7) after adjusting for patient age, injury severity, and amount of blood
      transfused during resuscitation. In this study population, obesity was also
      associated with increased length of ICU and hospital stay but not death.
      CONCLUSIONS: Obese patients are at increased risk of postinjury MOF. Study of the
      obesity-related inflammatory profile could provide additional insight into the
      pathogenesis of organ dysfunction and identify therapeutic targets for both obese
      and nonobese patients. Increased morbidity and length of stay in obese trauma
      patients implies greater resource allocation for this population.

PMID- 17000400
TI  - Impact of Acinetobacter infection on the mortality of burn patients.
AB  - BACKGROUND: Acinetobacter calcoaceticus-baumannii complex (Acb) is recognized as
      an important cause of nosocomial infections. Although Acb can be associated with
      multidrug resistance, its impact on mortality in burn patients has not been fully
      elucidated. STUDY DESIGN: In a retrospective cohort study assessing medical
      records and microbiology laboratory data at a US military tertiary care burn
      center, we evaluated all patients admitted to the burn center between January
      2003 and November 2005. Data collected included age, severity of burn,
      comorbidities, length of stay, and survival to hospital discharge. In addition,
      microbiology data were reviewed to determine which patients were infected with
      Acb during this time frame. These data were then used to compare patients
      infected with Acb to patients not infected. Multivariate analysis using logistic
      regression was performed to determine which patient characteristics were
      associated with increased mortality. RESULTS: There were 802 patients included in
      the study. Fifty-nine patients met the case definition for infection. An
      additional 52 patients were found to be colonized with Acb. Patients with Acb
      infection had more severe burns and comorbidities, and had longer lengths of stay
      compared with patients without Acb or those with Acb colonization. Mortality in
      infected patients was higher compared with those without infection (relative risk
      = 2.86, p = 0.001). On multivariate analysis, infection with Acb was not
      statistically associated with mortality. CONCLUSIONS: Multidrug-resistant Acb is
      a common cause of nosocomial infection in the burn patient population. Despite
      this, it does not independently affect mortality.

PMID- 17000401
TI  - Evolution to video-assisted thoracic surgery lobectomy after training: initial
      results of the first 30 patients.
AB  - BACKGROUND: In early-stage lung cancer, evidence is accumulating for the benefits
      of lobectomy by video-assisted thoracic surgery (VATS) over open lobectomy. Few
      thoracic training programs offer sufficient experience in this technically
      demanding procedure. This article describes the evolution of a new graduate's
      practice from open thoracotomy to VATS lobectomy. STUDY DESIGN: Our model
      involves a transition in technique from posterolateral thoracotomy to muscle
      sparing thoracotomy and, ultimately, to VATS lobectomy. This approach was
      evaluated by examining outcomes of open thoracotomy patients before VATS
      lobectomy and outcomes of the initial 30 VATS patients. Data were collected
      prospectively. RESULTS: Before undertaking VATS lobectomy, 94 major pulmonary
      resections were performed by thoracotomy. Mortality was 1.2% for lobectomy and 0%
      for pneumonectomy. Use of the muscle-sparing thoracotomy increased from 17% of
      patients in the first half to 70% in the latter half of this group. For the first
      30 VATS lobectomy patients, the mean operative time was 168 minutes. Median blood
      loss was 200 mL. Conversion rate to open thoracotomy was 13.3%. Mortality was
      3.3% and morbidity was 26.7%. After short-term followup (mean followup 16
      months), overall survival for stage I lung cancer was 96%. CONCLUSIONS: With our
      approach, new graduates of thoracic surgery programs can safely transition to
      VATS lobectomy. Gaining experience with the lateral muscle-sparing thoracotomy is
      an important step in the transition, as it offers similar operative exposure.
      Longterm disease-free and overall survival data are needed to evaluate our
      oncologic efficacy with this approach.

PMID- 17000402
TI  - Association of race and gender with general surgeons' annual incomes.
AB  - BACKGROUND: Specialty, work effort, and gender have been shown to be associated
      with physicians' annual incomes. Although female plastic, oral, and
      cardiothoracic surgeons have been shown to have lower incomes than their male
      counterparts, differences in incomes attributable to gender or race among general
      surgeons have not been evaluated. STUDY DESIGN: We used survey responses
      collected during the 1990s from 771 actively practicing general surgeons and
      linear regression modeling to determine the association of race and gender with
      general surgeons' annual incomes after controlling for work effort, provider
      characteristics, and practice characteristics. RESULTS: Compared with Caucasian
      men, both African-American male and Caucasian female general surgeons reported
      having fewer patient visits (10% fewer and 17% fewer, respectively), but working
      more annual hours (14% more and 6.7% more, respectively). Caucasian women were
      more likely than the other groups to be nonpractice-owner employees. African
      American men and Caucasian women were less likely than their Caucasian male
      counterparts to be board certified. After adjustment for work effort, provider
      characteristics, and practice characteristics, African-American men's mean annual
      income was $248,048, or $49,205 (17%) lower than that for Caucasian men (95% CI:
      $129,645 lower to $31,236 higher, p=0.2); Caucasian women's was $233,397, or
      $63,856 (21%) lower (95% CI: $120,367 to $7,345 lower, p=0.03). CONCLUSIONS:
      During the 1990s, among Caucasian general surgeons, female gender was associated
      with considerably lower annual incomes; among male general surgeons, African
      American race was associated with lower annual incomes, but not substantially so.
      These findings warrant additional exploration to ensure that income differences
      among physicians are not unjustly determined by race or gender.

PMID- 17000403
TI  - Surgeons managing conflict: a framework for understanding the challenge.

PMID- 17000404
TI  - The escaped worm.

PMID- 17000405
TI  - Recurrent attacks of acute pancreatitis from Ascaris in the common bile duct.

PMID- 17000406
TI  - A 30-year odyssey with the umbilical vein graft.

PMID- 17000408
TI  - Obviate.

PMID- 17000407
TI  - Ultrasonography in surgical residency.

PMID- 17000409
TI  - Human immunodeficiency virus-positive patient with bilateral corneal endothelial
      deposits.
AB  - BACKGROUND: Ocular disorders associated with the human immunodeficiency virus are
      numerous as are ocular side effects from medications used to treat all of the
      manifestations of the virus. This report presents a unique case of bilateral,
      peripheral, and corneal endothelial deposits that may be a result of either the
      human immunodeficiency virus or the medication rifabutin. Rifabutin was the only
      medication prescribed that is known to cause endothelial deposits. Rifabutin is
      part of a multidrug therapy to prevent or treat Mycobacterium avium complex, a
      common pulmonary disease of immunocompromised individuals. CASE REPORT: A 69-year
      old man with a 20-year history of being human immunodeficiency virus-positive
      presented with bilateral, asymptomatic, peripheral, and corneal endothelial
      deposits of unknown etiology. Literature research suggested that the deposits did
      not appear like cytomegalovirus retinitis-related deposits but rather a variant
      of rifabutin-associated deposits. CONCLUSIONS: These rifabutin-associated
      deposits differed from known rifabutin-associated deposits previously reported in
      the literature. These deposits have increased in pigmentation and density 5 years
      after the patient discontinued the drug. This case may represent another
      variation of rifabutin-associated endothelial deposits. Knowledge of human
      immunodeficiency virus and all the associated ocular findings (owing to both the
      condition and its treatment) is important, because the length of time patients
      are living with human immunodeficiency virus is increasing.

PMID- 17000410
TI  - Rapid growth of pterygium after photorefractive keratectomy.
AB  - BACKGROUND: A pterygium is a fibrovascular overgrowth of degenerative conjunctiva
      over the limbus onto the cornea. The risk factors for pterygium development
      include exposure to ultraviolet (UV) light, dust, wind, heat, dryness, and smoke.
      As far as we are aware, rapid growth of pterygium secondary to photorefractive
      keratectomy (PRK) has not been reported previously. CASE REPORT: A 49-year-old
      man presented with blurring vision in the left eye. The patient had undergone PRK
      in both eyes at another surgical center 11 months prior. Examination found a
      pterygium extending 3 mm over the corneal midline and covering 60% to 70% of the
      cornea. Information regarding the extent of the pterygium in the left eye was
      limited; however, preoperative drawings showed a moderate extension of about a 3
      mm encroachment into the nasal cornea. However, the patient stated that the 2
      sides "looked similar" before PRK and that the right side remained "pretty small"
      after surgery. CONCLUSION: Several growth factors have been detected in the
      cornea during the recovery from PRK surgery. Those growth factors might have the
      potential to exacerbate the growth of a pterygium. Further studies are needed to
      draw any conclusion regarding the consequence of PRK surgery on the growth of a
      pterygium so patients can be better informed and managed. As eye care providers,
      we should be aware of the potential that rapid growth of a pterygium may occur
      after PRK.

PMID- 17000411
TI  - Therapeutic options for the management of early neurotrophic keratopathy: a case
      report and review.
AB  - BACKGROUND: Neurotrophic keratopathy is caused by the loss of corneal sensation
      secondary to impaired trigeminal nerve function. Timely and appropriate action is
      required in the management of this condition to prevent serious complications
      such as corneal ulceration, perforation, and loss of vision. The role of
      immunomodulating agents such as cyclosporine as a therapeutic option and a review
      of several future treatment modalities are discussed. CASE REPORT: A 46-year-old
      black woman with a noted history of recurrent herpes simplex virus-1 keratitis
      and secondary neurotrophic keratopathy in the left eye was examined. She reported
      that another physician had treated her for this condition over the last 6 months.
      Her treatment regimen consisted of a bandage contact lens, antibiotic solution,
      and artificial tears. Best-corrected visual acuities were 20/20 in the right eye
      and 20/25 in the left eye. Biomicroscopy evaluation found punctate keratitis in
      both eyes and neurotrophic keratopathy with an area of pinpoint epithelial defect
      in the left eye. Restasis (0.05% cyclosporine ophthalmic emulsion; Allergan,
      Irvine, California) bid was added to her medical regimen. Within 4 weeks of
      starting Restasis therapy, the epithelial defect had resolved, and she was
      advised to discontinue both the bandage lens and antibiotic solution. She was
      ultimately discharged on a continued regimen of Restasis twice a day and
      lubricating drops as needed with scheduled follow-up every 3 months. CONCLUSION:
      Management of neurotrophic keratopathy requires decisive action. Early treatment
      intervention is important to help avoid severe complications. The use of
      immunomodulating agents (topical cyclosporine) in the early stage of management
      should be considered.

PMID- 17000412
TI  - A prospective study of the EYEPORT vision training system.
AB  - BACKGROUND: The purpose of this study was to determine if vision training with
      the EYEPORT system affects vision and reading performance. (Subsequent to this
      study, the "E.Y.E." has been renamed "EYEPORT") METHODS: College students with
      normal vision (n = 31) participated in a blind, crossover study to assess within
      subject and between-group effects of EYEPORT training. Half the subjects
      initially underwent training (10 minutes per day, 6 days a week for 3 weeks), and
      then crossed over to the no-train control condition (3 weeks); the other half
      underwent the reverse sequence. Vision and reading performance were assessed at
      baseline, 3 weeks, and 6 weeks. RESULTS: Multivariate analyses (Hotelling's T2)
      found small improvements in vergence and accommodative facility, reading
      performance, and stereopsis response time after EYEPORT training (P < 0.025).
      Enhancements in reading performance and vergence facility were still present 3
      weeks after cessation of training (P < 0.001). CONCLUSIONS: The EYEPORT training
      system shows potential to enhance visual performance and reading ability. Studies
      are underway to assess its efficacy in symptomatic populations.

PMID- 17000414
TI  - Health care for children and youth in the United States: annual report on
      patterns of coverage, utilization, quality, and expenditures by a county level of
      urban influence.
AB  - OBJECTIVE: To examine child and hospital demographics and children's health care
      coverage, use, expenditures, and quality by a county-level measure of urban
      influence. METHODS: Two national health care databases serve as the sources of
      data for this report: the 2002 Medical Expenditure Panel Survey (MEPS) and the
      2002 Nationwide Inpatient Sample (NIS) and State Inpatient Databases (SID) from
      the Healthcare Cost and Utilization Project (HCUP). In both data sets, county
      urbanicity is defined by use of a collapsed version of the 2003 Urban Influence
      Codes, to distinguish among children residing in and hospitals located in large
      metropolitan (metro) counties, small metro counties, micropolitan counties, and
      noncore counties. RESULTS: Demographics. In large metro counties, greater
      percentages of the child population are Hispanic or black non-Hispanic than in
      small metro, micropolitan, and noncore counties; in micropolitan and noncore
      counties, higher proportions of children are below 200% of the federal poverty
      level than in large metro and small metro counties. Noncore areas have a greater
      percentage of children in fair or poor health compared with those in small metro
      and micropolitan counties. Most hospitals are located in large and small metro
      areas, and large metro areas have a higher proportion of teaching hospitals
      compared with other areas. Health care. In general, there were no overall
      differences by place of residence in the proportion of children with and without
      insurance, although differences emerged in subpopulations within Urban Influence
      Code types. Hispanic children residing in large metro counties were more likely
      to be uninsured than those in small metro counties. Overall, the proportion of
      children with at least one dental visit was larger in small metro areas compared
      with both large metro and noncore areas. The proportion of children with
      medicines prescribed was generally lower in large metro areas compared with all
      other areas both overall and among subpopulations of children. Children in
      noncore areas were more likely to have a hospital inpatient stay and any
      emergency department use compared with children in large metro areas. Children in
      large metro counties had longer average inpatient stays and a higher hospital
      inpatient charge per day compared with children in all other counties. Although
      most hospitalizations for children from large metro areas occurred in large metro
      areas, over half of hospitalizations for noncore children occurred outside of
      noncore counties. Further, children from noncore counties appear to be
      hospitalized for ambulatory sensitive conditions more than children from all
      other areas. CONCLUSIONS: County-level data analyses performed using a collapsed
      version of the Urban Influence Codes with MEPS and HCUP data shed additional
      light on the health care patterns for children that were not previously evident
      when only the dichotomous metropolitan/nonmetropolitan geographic schema was
      used.

PMID- 17000415
TI  - Rural areas and children's health care coverage, use, expenditures, and quality:
      policy implications.

PMID- 17000416
TI  - 2006 George Armstrong Lecture: Who's worrying about the children--and what are
      they doing about it?

PMID- 17000417
TI  - 2006 Ambulatory Pediatric Association presidential address. Sustainable,
      renewable educational "energy".

PMID- 17000418
TI  - Early middle ear effusion and school achievement at age seven years.
AB  - OBJECTIVE: This study tested the hypothesis that children with early persistent
      middle ear effusion (MEE) are at risk for later deficits in academic performance.
      METHODS: We recruited 698 newborns and monitored them for MEE every 2 to 4 weeks
      at home until age 3 years. At age 7 years, it was possible to obtain school data
      for 226 children. Tests included the Iowa Tests of Basic Skills or the Stanford
      Achievement tests, the Woodcock Reading Mastery Tests, and the Woodcock-Johnson
      Tests of Achievement. RESULTS: There was no significant relationship between
      early MEE and measures of school achievement as shown by correlations or multiple
      regression. Differences between extreme MEE groups were not significant. School
      achievement was strongly associated with ethnicity, home environment, and
      socioeconomic status. CONCLUSIONS: Early persistent MEE does not appear to affect
      achievement in school at age 7 years.

PMID- 17000419
TI  - Predicting children's blood lead levels from exposure to school drinking water in
      Seattle, Washington, USA.
AB  - OBJECTIVE: Lead exposure through drinking water is of increasing interest with
      little known about its potential childhood health impact. In 2004, school testing
      in Seattle, Washington, found lead concentrations in drinking water that exceeded
      national guidelines (>20 ppb). On the basis of these data, we estimated potential
      blood lead levels (BLLs) in elementary school children to better understand the
      potential health risks posed by these exposures. METHODS: We used the US
      Environmental Protection Agency Integrated Uptake Biokinetic Model for Lead in
      Children to predict geometric mean BLLs. We modeled typical-case and worst-case
      scenarios for children in 71 elementary schools on the basis of drinking water
      lead concentrations results from 2004. RESULTS: The estimated geometric mean BLLs
      under a typical scenario for each school ranged from 1.6 to 2.5 microg/dL. The
      worst-case scenario predicted geometric mean BLLs ranging from 1.7 to 5.0
      microg/dL. All modeling yielded predicted BLLs well below the Centers for Disease
      Control and Prevention's public health goal of <10 microg/dL. CONCLUSIONS: Our
      modeling suggests drinking water exposures up to 10-15 times the Environmental
      Protection Agency guideline are unlikely to result in BLLs exceeding the current
      guidelines of the Centers for Disease Control and Prevention in the absence of
      other significant exposure sources. In Seattle, elevated school drinking water
      lead concentrations are not a significant source of lead exposure in school-age
      children. Further characterization of drinking water impacts are merited only if
      younger-age children are consuming water or if water lead concentrations are
      higher than those in this study.

PMID- 17000420
TI  - Children's visits to providers of complementary and alternative medicine in San
      Diego.
AB  - OBJECTIVE: Increased attention has been focused on the growing use of
      complementary and alternative medicine (CAM); however, few studies have included
      children in the general US population. The present study investigated children's
      visits to CAM providers and factors associated with these visits. METHODS:
      Analysis of cross-sectional data from the 2001 United Way Outcomes and Community
      Impact Program telephone survey, a representative sample of households in San
      Diego County, California. We selected households with children younger than 19
      years of age (N = 1104). Parents reported on children's CAM visits in the past
      year. RESULTS: Approximately 23% of parents reported that their child saw a CAM
      provider in the past 12 months. CAM care was sought for sick and routine care.
      Children of white parents had greater odds of having a CAM visit in the past year
      compared with children whose parents were Hispanic (adjusted odds ratio 1.71, 95%
      confidence interval [95% CI] 1.11-2.63). Children whose parents were college
      graduates had a greater likelihood of seeing a CAM provider than children of
      parents with high school education (adjusted odds ratio = 1.82, 95% CI 1.19
      2.79). Children who were insured were also more likely to have CAM visits than
      uninsured children (adjusted odds ratio = 2.32, 95% CI 1.04-5.21). CONCLUSIONS:
      Visits to CAM providers were much more common among children in the general San
      Diego population compared with 1996 national estimates. Pediatric health care
      providers should remain aware that their patients may be using CAM so they can
      provide coordinated care.

PMID- 17000422
TI  - Raman spectroscopic studies on the interaction between counterion and polyion.
AB  - The interaction between alkali metal ions and the polyacrylate ion was
      investigated by means of Raman spectroscopy. in comparison with the Raman spectra
      of propionate salts. The Raman bands due to the metal-oxygen bond were not
      apparent and no significant difference was observed among the Raman spectra of
      several univalent salts of polyacrylate. except in the case of the lithium salt.
      The apparent degree of dissociation of lithium polyacrylate, as determined from
      the relative intensity of a specific band characteristic of the carboxylate ion,
      was lower than those of the other alkali metal salts. It is concluded from the
      Raman data that the electrostatic interaction between counterions and a polyion
      is not specifically modified by forces of a nonionic nature. Moreover, it is
      pointed out that the local conformation of polyacrylate changes gradually with
      the degree of neutralization, but that the change is not like a conformational
      transition between globular and random coil forms.

PMID- 17000421
TI  - Relationship of childhood behavior disorders to weight gain from childhood into
      adulthood.
AB  - OBJECTIVE: Obesity and behavior disorders are important conditions that affect
      the health of children and adolescents; some evidence suggests that they are
      associated. However, these relationships have not been studied longitudinally
      from childhood to adulthood. We investigated childhood to adulthood weight change
      associated with attention-deficit and disruptive behavior disorders. METHODS: We
      analyzed data from a prospective cohort study in which 655 individuals observed
      before age 16.6 years, and assessed in 1983 (when aged 9.1 to 16.6 years), 1985
      1986 (when 11.1 to 20.8 years), 1991-1994 (when 16.6 to 26.9 years), and 2001
      2003 (when 27.7 to 38.3 years). Attention-deficit/hyperactivity disorder,
      oppositional defiant disorder, and conduct disorder (collectively, "disruptive
      disorders") were assessed by trained interviewers who used the Diagnostic
      Interview Schedule for Children. We evaluated the association of disruptive
      disorders (assessed when youth were <16.6 years) with longitudinal body mass
      index (BMI) z scores from childhood to adulthood using linear mixed-effects
      models. RESULTS: Female subjects with disruptive disorders were estimated, at all
      ages, to have mean BMI z scores 0.23 (95% confidence interval, 0.03-0.44) units
      higher than female subjects without disruptive disorders. Male subjects with
      disruptive disorders were estimated, at all ages, to have mean BMI z scores 0.20
      (95% confidence interval, 0.00-0.39) units higher than male subjects without
      disruptive disorders. For male and female subjects, annual BMI z-score change was
      statistically unrelated to disruptive disorder history. CONCLUSIONS: Disruptive
      disorders were associated with elevated weight status that was maintained from
      childhood into adulthood. These findings suggest that associations between
      behavior disorders and increased weight begin early in childhood and may have
      lifelong health effects.

PMID- 17000423
TI  - Steady-state fluorescence polarization in planar lipid membranes. Experimental
      and theoretical analysis of the fluorophores 8-anilino-1-naphthalenesulfonate,
      1,6-Diphenyl-1,3,5-hexatriene, dansyllysine-valinomycin and n-(9-anthroyloxy)
      fatty acids.
AB  - In continuation of earlier work, the steady-state fluorescence polarization in a
      globally oriented system of planar lipid membranes was analyzed experimentally
      and theoretically for the fluorophores 8-anilino-1-naphthalenesulfonate, 1,6
      diphenyl-1,3, 5-hexatriene, dansyllysine-valinomycin and n-(9-anthroyloxy) fatty
      acids. The theoretical analyses of experiments were mainly done in terms of the
      mean orientation of transition moments with respect to the membrane normal, an
      angle describing the region of hindered rotational diffusion and the coefficients
      of rotational diffusion perpendicular to the membrane and around the membrane
      normal. The nonvanishing angle between the moments of absorption and emission was
      taken into account. In the case of n-(9-anthroyloxy) fatty acids it was found
      that the orientational disorder increases significantly with the depth of the
      fluorophore within the membrane. In order to compare with recent results from
      time-dependent fluorescent polarization in globally isotropic membrane
      suspensions and with 2H-NMR experiments, the second moment ('order parameter') of
      the steady-state orientational distribution of absorption dipoles was calculated.
      For all fluorophores the theoretical analysis indicates a preferred orientation
      of absorption moments within the membrane plane.

PMID- 17000424
TI  - Thermochemistry of aqueous solutions of alkylated nucleic acid bases. IV.
      Enthalpies of hydration of 5-alkyluracils.
AB  - Enthalpies of sublimation, DeltaH degrees (subl) and of solution in water, DeltaH
      degrees (sol) were determined for a series of crystalline 1,3-dimethyl-uracil
      derivatives substituted at the C5-ring carbon atom with alkyl groups (
      C(n)H(2n+1), n = 2-4) and some of their C(5.6)-cyclooligomethylene analogues (
      (CH2)(n)-, n = 3-5). From these data. enthalpies of hydration DeltaH degrees
      (hydr)= DeltaH degrees (sol) - DeltaH degrees (subl) were calculated and
      corrected for energies of cavity formation in pure liquid water in order to
      obtain enthalpies of interaction, DeltaH degrees (int) of the solutes with their
      hydration shells. The latter are discussed together with the recalculated DeltaH
      degrees (int) for variously methylated uracils, obtained previously according to
      a simplified correction procedure, in terms of perturbations in the energy and
      scheme of hydration of the diketopyrimidine ring brought about by alkyl
      substitution. It was found that each -CH2-group added with an alkyl substitution
      contributes favorably about -20 kJ mol(-1) toDeltaH degrees (int). This
      contribution is partially cancelled by the unfavorable contribution to DeltaH
      degrees (int) connected with removal of some water molecules bound in the first
      and subsequent hydration layers by an alkyl substituent. This is particularly
      evident on substitution at the polar side of the diketopyrimidine ring on which
      water molecules are expected to be bound specifically.

PMID- 17000425
TI  - Mass-spectrometric investigations on hydration of nucleic acid components in
      vacuum.
AB  - Association reactions between water and alkylated uracils. occurring under field
      ionization conditions in a mass spectrometer at the tungsten point emitter
      surface, were studied at several temperatures. The origin of peaks observed in
      the mass spectra at m/e ratios corresponding to M+H and M+H-H2O were attributed
      to M-H2O and M-(H2O)2 hydrates, respectively, hydrogen-bonded via carbonyl groups
      of the diketopyrimidines (M) investigated. The appearance of these ions is
      explained in terms of the field-ionization mechanism of the neutral hydrates
      involving intramolecular H+ transfer and concomitant release of the OH+ radical.
      Measurements of the relative peak intensities allowed the calculation of apparent
      equilibrium constants. K(ass). for the association reactions, and hence the
      respective van't Hoff enthalpies of hydrat'on. The latter are discussed in
      connection with the available quantum-mechanical hydration energies for specific
      groups of respective canonical nucleic acid bases and experimental enthalpies of
      hydration of alkylated uracils with water. Specific hydration is estimated to
      contribute about 15-20% to the total enthalpy of interaction of the solutes with
      their hydration shells.

PMID- 17000426
TI  - The viscosity increment for ellipsoids of revolution. Some observations on the
      Simha formula.
AB  - Outstanding uncertainties in the widely employed Simha (J. Phys. Chem. 44 (1940)
      25) function for the viscosity increment r of macromolecules as modelled by
      axially symmetric ellipsoids are resolved. A simple development of the analysis
      also reveals an interesting relationship between nu and the translational
      frictional property of macromolecules.

PMID- 17000427
TI  - Heavy metal-nucleotide interactions. 15. Reactions of calf thymus DNA with the
      electrophiles methylmercury(II) nitrate, cis-dichlorodiammineplatinum(II), and
      trans-dichlorodiammineplatinum(II) studied using Raman difference spectroscopy.
      Evidence for the formation of c-DNA upon metalation.
AB  - This study details the reactions of the electrophiles CH3Hg(NO3), cis
      [PtCl2(NH3)2] (cis-DDP) and trans-[PtCl2(NH3)2] (trans-DDP) with calf thymus DNA
      using Raman and Raman difference spectroscopy. The order of CH3Hg(II) binding to
      calf thymus DNA is G > T > C > A. The electrophilic attack of cis- and trans-DDP
      on calf thymus DNA produces different orders of binding: cis-DDP-G>C
      approximately AT, trans-DDP-G approximately C approximately AT. The reaction of
      CH3Hg(II) with DNA results in a decrease in the percentage of B-form DNA. whereas
      the reactions of cis- and trans-DDP with DNA decrease the percentage of B-DNA and
      cause the formation of C-DNA structure.

PMID- 17000428
TI  - Determination of microscopic ionization constants and microscopic stacking
      equilibrium quotients of adenylyl(3' --> 5')adenosine.
AB  - Using the basic ionization constants for a pair of isomers, m1ApA and Apm1A, and
      the measured values for the overlapping pK values of ApA, the microscopic
      ionization constants and intramolecular stacking quotients for the monoprotonated
      ApA were estimated. The results indicate that, in contrast to the case of GpG,
      ApA did not exhibit preferential protonation on either site of 3'- and 5'-linked
      nucleoside bases and neither enhanced nor diminished stacking was observed for
      ApA and ApA as compared to ApA.

PMID- 17000429
TI  - Site binding as a local equilibrium. Mn2+ binding to poly(acrylic acid) as a
      function of the degree of ionization.
AB  - Mn2+ binding to poly(acrylic acid) at different degrees of ionization, alpha, has
      been studied from the frequency dependence of the water protons' relaxation rates
      T1(-1) and T2(-1). Site binding is treated as an equilibrium with the
      concentration of free ions at the immediate vicinity (CIV) of the polyion. The
      CIV is calculated as the solution of the Poisson-Boltzmann equation at the
      surface of the cylindrical polyion. A single value of K is shown to fit the
      results at all values of alpha. The amount of site binding is higher than the
      total amount of condensed divalent counterions predicted for a finite polyion
      concentration in the presence of monovalent counterions by Manning's theory.

PMID- 17000430
TI  - Activation enthalpy of diffusion for well fractionated dextrans in aqueous
      solutions.
AB  - Interdiffusion coefficients have been determined for seven well defined dextran
      fractions in aqueous solutions at 20, 25, 30 and 35 degrees C. For dextrans with
      number average molecular weights (Mn) greater than about 20 000, a plot of the
      apparent activation energy of diffusion (ED) against Mn is given by: ED = 2.763 x
      10(-5) Mn + 3.38. Similarly, for weigh molecular weight (Mw): ED = 1.889 x 10(-5)
      Mw + 3.61. The extrapolated ED values (3.38 and 3.61) are in reasonably good
      agreement with published data for the activation energy of self-diffusion for
      water.

PMID- 17000431
TI  - Intramolecular alpha-helix-beta-structure-random coil transition in polypeptides.
      I. Equilibrium case.
AB  - The present paper is devoted to the study of the conformational transition of
      polypeptides which are capable of forming alpha-helix, beta-structure and random
      coil conformations with the finite homogeneous chain model. The experimental
      results on the surfactant-induced conformational change of poly(L-lysine) can be
      well described by the present model assuming cooperative binding of the
      surfactant ions to the polypeptide side groups.

PMID- 17000432
TI  - Intramolecular alpha-helix-beta-structure-random coil transition in polypeptides.
      II. Dynamic case.
AB  - The conformational changes of polypeptides which are capable of forming the alpha
      helix. beta-structure and random coil (or the unordered) conformations are
      discussed. The kinetics of this system are studied as the time evolution of the
      probabilities describing the conformational states of the system. The time
      behavior of the average numbers of the alpha-helix and the beta-structure reveals
      the existence of intermediate states which are not found and not stable at
      equilibrium. These intermediates make the kinetics of this system more complex.
      Such situations can occur in protein folding and unfolding processes in such a
      way that a conformation absent in the tertiary structure appears in the
      intermediate stages and disappears finally, and the time course of the reaction
      is described by the sum of two or more exponential terms, in other words, the
      protein folding and unfolding processes display multiphasic kinetics. These
      intermediates, which are formed by short-range interactions, may usually be
      destroyed but sometimes can be stabilized by medium- and long-range interactions
      and remain stable for a fairly long time in the process of renaturation in real
      proteins.

PMID- 17000433
TI  - The random walk description for isotope exchange in a polypeptide.
AB  - Isotope exchange in a polypeptide is considered from the point of view in which
      the boundary point between helix and coil regions of a polypeptide behaves like a
      weakly asymmetric random walker. We assume that the boundary point is reflected
      completely at the ends of a polypeptide. The equilibrium fraction of helix region
      is obtained under this assumption, and this is also confirmed by computer
      simulation. The experimental results of isotope exchange can be explained in this
      situation. On the other hand. the rate constant of exchange of a residue given by
      experiments can also be explained by another assumption, as considered before (M.
      Fujiwara and N. Saito, Polym. J. 9 (1977) 625.), in which the nucleations of coil
      states take place in the helix region. Which of the two is of major importance is
      left to further studies.

PMID- 17000434
TI  - The effect of the propagation coefficient on size distribution in micellar
      systems.
AB  - In this study the effect of the propagation coefficient on the molar distribution
      function in a modified shell model for micellar systems was examined. The
      sharpness of the micelle size distribution boundary was found to depend less on
      the degree of polymerization, n, than on the propagation coefficient, P. Although
      Kegeles (J. Phys. Chem. 83 (1979) 1728) has reported a marked sharpening of the
      distribution boundary when P = 2.0. we found the boundary to be fairly broad at
      this point. However, as values of the propagation coefficient were increased from
      3 to 10, the micelle distribution boundary became increasingly sharp. The
      possibility of such a change in the reaction boundary arising from a structural
      transition, accompanied by a change in the rate of dissociation of monomer from
      the shell, is also discussed.

PMID- 17000435
TI  - Simulation of convoluted and exact emission anisotropy decay profiles.
AB  - We have Simulated the convolution of the emission anisotropy decay function with
      both a delta-pulse excitation function (exact solution) and a pulse function of
      either Gaussian or other functional form. It can be readily shown that
      convolution with a pulse of finite width leads to lower r0 values (anisotropy at
      time zero). Especially in the case of short-lived fluorescence, it can be
      demonstrated that the convoluted anisotropy lags behind the exact anisotropy
      leading to longer apparent rotational correlation times. Contour plots of r
      corrections as a function of both fluorescence lifetime and rotational
      correlation time were constructed for two different pulse profiles. Inspection of
      these contour diagrams can lead to an estimate of the relative error involved,
      when anisotropy data are not deconvoluted.

PMID- 17000436
TI  - Ion binding or condensation to polyelectrolytes? A detailed comparison, on the
      example of sodium heparinate.
AB  - A modified Poisson-Boltzmann treatment is applied to aqueous solutions of sodium
      heparinate, in the presence of added salts (NaCl, LiCl, KCl, CaCl2). The results
      show that 23Na-NMR line widths for the counterions are determined nearly
      exclusively by Na+ in the immediate vicinity of the linear polyelectrolyte.
      Hence, two-state treatments, despite their crude character, can reproduce such
      experimental data rather well.

PMID- 17000437
TI  - Conformational flexibility of membrane proteins in electric fields. I.
      Ultraviolet absorbance and light scattering of bacteriorhodopsin in purple
      membranes.
AB  - Bacteriorhodopsin of halobacterial purple membranes exhibits conformational
      flexibility in high electric field pulses (1-30 x 10(5) V m(-1), 1-100 micros).
      High-field electric dichroism data of purple membrane suspensions indicate two
      kinetically different structural transitions within the protein; involving a
      rapid (approximately 1 micros) concerted change in the orientation of both
      retinal and tyrosine and/or tryptophan side chains concomitant with alterations
      in the local protein environment of these chromophores. as well as slower changes
      (approximately 100 micros) of the microenvironment of aromatic amino acid
      residues concomitant with pK changes in at least two types of proton-binding
      sites. Light scattering data are consistent with the maintenance of the random
      distribution of the membrane discs within the short duration of the applied
      electric fields. The kinetics of the electro-optic signals and the steep
      dependence of the relaxation amplitudes on the electric field strength suggest a
      saturable induced-dipole mechanism and a rather large reaction dipole moment of
      1.1 x 10(-25) C m ( = 3.3 x 10(4) debye) per cooperative unit at E = 1.3 x 10(5)
      V m(-1), which is indicative of appreciable cooperativity in the probably
      unidirectional transversal displacement of ionic groups on the surfaces of and
      within the bacteriorhodopsin proteins of the membrane lattice. The electro-optic
      data of bacteriorhodopsin are suggestive of a possibly general, induced-dipole
      mechanism for electric field-dependent structural changes in membrane transport
      proteins such as the gating proteins in excitable membranes or the ATP
      synthetases.

PMID- 17000438
TI  - Aggregation of chlorophylls in monolayers. V. The effect of water on chlorophyll
      a and chlorophyll b in mono and multilayer arrays.
AB  - The nature of the interactions between water molecules and monolayers and
      multilayers of chlorophyll a (Chl a), and monolayers and multilayers of Chl b.
      obtained by the Langmuir-Blodgett technique, is examined by infrared
      spectroscopy. Following deposition of the monolayer or multilayer of Chl a or Chl
      b onto a plate, repetitive scans showed some modifications in the infrared
      spectra which are interpreted as a reorganization of the molecules as some water
      molecules leave the array. Drying the sample further modifies the spectra, which
      indicates the departure of more tenacious water molecules. Putting the sample in
      a moist atmosphere does not restore the original spectrum. This is an indication
      of a nonreversibie reorganization in the chlorophyll array. The spectra of the
      monolayer of chlorophyll are much more complicated than those of the multilayer,
      owing to the nonintegrating effect of the monolayer, which reveals the perturbing
      effect of the different dielectric milieux on each functional group. On the basis
      of the analysis of the spectra and the information gathered from the surface
      pressure isotherms, a model is proposed for the monolayer arrangement at the
      air/water interface which implies two set of dimers of water per molecule of
      chlorophyll. One pair of dimers constitutes the water of the first kind and is
      composed of vapor-like dimers. This kind of water is situated between the
      porphyrin planes of chlorophyll molecules and is easily removed from the
      monolayer. The second pair of dimers is composed of water of the second and third
      kinds situated between the Mg atom of the chlorophyll molecules and the water of
      the subphase. The second kind of water is closest to the Mg atom and is the most
      difficult one to remove. The third kind of water is closest to the surface and
      its mobility is intermediate between that of water of the first kind and that of
      water of the second kind. Comparing the infrared spectra of a freshly prepared
      monolayers of Chl a with the resonance Raman spectra of intact chloroplasts (M.
      Lutz, Biochim. Biophys. Acta 460 (1977) 408), we notice great similarities. This
      is an indication that the model we propose for the monolayer of Chl a could play
      an important role in the chloroplast.

PMID- 17000439
TI  - 'Steady/equilibrium approximation' in relaxation and fluctuation. II.
      Mathematical theory of approximations in first-order reaction.
AB  - A mathematical theory of the steady/equilibrium approximation for first-order
      reactions is presented. This gives the theoretical basis for the methods of
      simplifying the complex first-order reactions described in the preceding work The
      steady/equilibrium relation holds on every fast component after a proper
      inducation period T degrees T degrees is either of O(1) or less, or nearly of
      O(1/epsilon) depending on the reaction scheme and on the initial condition but is
      always less than O(1/epsilon) (as in the preceding paper [1], we use the symbol
      O(1) to denote a positive number of the order of unity). In the open group, the
      determinant of the submatrix M(p), representing the interconversion between the
      fast components in the group and their dissipation, is of O(1). The concentration
      of the fast components in the open group can thus be expressed as a linear
      combination of those components neighboring the group after the establishment of
      a steady/equilibrium relation, and can be eliminated from the reaction scheme
      leaving the pathway through them. On the other hand, in the closed group the
      determinant of Mp is of O(epsilon) or less and the components in the group are in
      quasi equilibrium with each other after T degrees . They are eliminated from the
      reaction scheme leaving the sum of the components in the closed group as a slow
      component.

PMID- 17000440
TI  - Generalized finite element solution to one-dimensional flux problems.
AB  - A finite element numerical solution to the general one-dimensional flow equation
      is derived in a form that provides a convenient and general means to simulate a
      wide variety of one-dimensional flow techniques of interest to biological
      scientists, e.g., ultracentrifugation, electrophoresis, chromatography, etc.
      Diverse physical models defined in terms of column geometry, solute interactions,
      and the dependence of transport parameters on column position, time, or
      concentrations of one or more solutes, can be accommodated. A particularly useful
      aspect of the formulation is that a wide variety of boundary conditions can be
      simply applied to the end result, without rederivation of the solution for each
      new case. The numerical solution is expressed as matrix equations that are
      sufficiently general so that incorporation of particular models can be effected
      by substitution of appropriate quantities into the final result.

PMID- 17000441
TI  - Correlation between the antitumor activity of a polysaccharide schizophyllan and
      its triple-helical conformation in dilute aqueous solution.
AB  - Eight samples of a polysaccharide schizophyllan ranging in weight-average
      molecular weight Mw (in water) from 5 x 10(3) to 1.3 x 10(5) were prepared and
      their antitumor activity (expressed in terms of the tumor inhibition ratio)
      against Sarcoma 180 ascites, intrinsic viscosities [eta], and gel-filtration
      chromatograms in aqueous solution were determined. The tumor inhibition ratio was
      essentially unity for samples with Mw higher than 9 x 10(4), but reduced to zero
      or even to a negative value when Mw was lower than 10(4). The [eta] data combined
      with the chromatographic data showed that above Mw approximately 9 x 10(4) the
      predominant species of schizophyllan in aqueous solution is the previously found
      rigid triple helix, whereas below Mw approximately 9 x 10(4) both triple helices
      and single chains coexist in the solution and the fraction of triple helices
      decreases monotonically to zero as Mw is decreased to 5 x 10(3). From these
      findings it was concluded that the antitumor potency of schizophyllan in water is
      related to the amount of triple helices relative to that of single chains.

PMID- 17000442
TI  - Application of capsule endoscopy in small intestine diseases: analysis of 28
      cases in Kaohsiung Medical University Hospital.
AB  - Capsule endoscopy (CE) is used to diagnose small intestine disease. Many studies
      have shown a better lesion detection rate in obscure gastrointestinal (GI)
      bleeding than with other surveyed techniques. Our study investigates the
      diagnostic value of CE in patients with suspicious small intestine diseases.
      Between October 2004 and January 2006, patients who had suspected small intestine
      disease underwent CE in Kaohsiung Medical University Hospital. Presenting
      symptoms included obscure GI bleeding, abdominal pain, diarrhea, microcytic
      anemia, and other indications. CE results were analyzed as a proportion of total
      lesion detection rate and also with regard to obscure GI bleeding and abdominal
      pain for analysis. A total of 28 patients, including 12 males and 16 females,
      were enrolled for CE examination. Overall, small intestine lesions were detected
      in 20 cases (71.4%), with negative findings in eight cases. For obscure GI
      bleeding, the total lesion detection rate was 85.7% (12 of 14 patients) but the
      diagnostic rate was only 35.7% (five of 14 cases). In patients with abdominal
      pain, four of seven (57.1%) had small intestine lesions. In conclusion, CE survey
      has a good lesion detection rate for small intestine disease, especially for
      patients with obscure GI bleeding, and is helpful in the diagnosis of unexplained
      abdominal pain.

PMID- 17000443
TI  - Appendicitis in children younger than 3 years of age: an 18-year experience.
AB  - Appendicitis in children younger than 3 years of age has always been of concern
      due to its low incidence and high perforation rate. In this study, we analyzed
      our experience and evaluated the factors contributing to the delay in diagnosis.
      During the last 18 years, there were nine children younger than 3 years of age
      who presented with appendicitis. Four of these patients visited our emergency
      department within 48 hours after the onset of symptoms, while the symptoms had
      already persisted for more than 48 hours in the remaining five patients before
      their arrival in our emergency department. Perforated appendicitis was found in
      all children. Once the perforation had occurred for more than 2 days, complaints
      of fever, abdominal distention, and diarrhea were common. Compared to patients
      with symptoms for less than 2 days, those with symptoms for more than 2 days were
      younger and had higher serum C-reactive protein levels, significantly longer
      operation time, duration of postoperative ileus and length of hospital stay (LOS)
      (p = 0.026, 0.014, 0.018, and 0.014, respectively). No mortality was noted in the
      entire series, but seven of the nine patients had one or more complications,
      which may have prolonged LOS; anemia and wound infections were the two most
      common problems. Since delayed diagnosis is common, a thorough understanding of
      the clinical course of perforated appendicitis is important. Fever, diarrhea, and
      abdominal distention seem to be late manifestations. Prolonged LOS, operation
      time, and postoperative complications may be reduced if the operation is
      performed earlier.

PMID- 17000444
TI  - Functional performance of Alzheimer's disease and vascular dementia in southern
      Taiwan.
AB  - This study investigated the functional performance of two major subtypes of
      dementia, Alzheimer's disease (AD) and vascular dementia (VaD), by the Functional
      Independence Measure (FIM), and to understand the need for assistance in
      performing activities of daily living. The subjects comprised 64 AD and 21 VaD
      patients who were recruited from two epidemiologic studies of dementia with a
      total of 3,931 community residents aged 65 years and above in southern Taiwan.
      The results showed that the severity of dementia was similar between the two
      groups. The mean score for AD was 82.7 and for VaD was 56.5 for total FIM (p <
      0.05), 61.6 and 41.7 for the motor dimension (p < 0.05), and 21.1 and 15.7 for
      the cognitive dimension (p < 0.05). There were significant differences (p < 0.01)
      between AD and VaD in six FIM items and borderline or marginal significance (p <
      0.05) in most of the FIM items. For AD patients, stairs, lower dressing, bathing,
      and tub/shower transfer were the most difficult items in the motor dimension, and
      it was memory in the cognitive dimension. For VaD patients, bathing, upper and
      lower dressing, and grooming were the most difficult items in the motor
      dimension, and it was problem solving in the cognitive dimension. VaD patients
      were more dependent on all FIM items and required more assistance than AD
      patients. The functional performances of dementia patients were significantly
      associated with dementia severity and subtypes, together accounting for 40% of
      the variability in total FIM. In conclusion, most dementia patients are dependent
      in daily activities and different types and severity of dementia lead to
      different disability profiles; individualized care is, therefore, most
      appropriate.

PMID- 17000445
TI  - Reproducibility of peripapillary retinal nerve fiber layer and macular retinal
      thickness measurements using optical coherence tomography.
AB  - We investigated the interoperator reproducibility of peripapillary retinal nerve
      fiber layer (RNFL) and macular retinal thickness measurements using optical
      coherence tomography (OCT) in healthy Taiwanese eyes. In this study, OCT-3 was
      used by three trained and experienced operators to measure peripapillary RNFL and
      macular retinal thickness in a randomly chosen single eye from each normal
      subject. Mean thickness levels and the differences in thickness measurements
      among the three operators were calculated and compared. The eyes of 39 subjects
      (24 females and 15 males) were enrolled. The mean age of the subjects was 30.4 +/
      16.1 years (range, 11-46 years). The mean pupil diameter after pupillary
      dilation was 7.4 +/- 0.6mm (range, 6-9 mm). Comparing peripapillary RNFL and
      macular retinal thickness measurements after pupillary dilation, there were no
      significant differences in: superior, inferior, temporal, and nasal peripapillary
      areas; 6 mm total macular volume and foveal thickness; and 1, 3 and 6 mm
      perifoveal areas among the three operators. In this study, OCT thickness
      measurements showed good interoperator reproducibility among three trained and
      experienced operators.

PMID- 17000446
TI  - Acute pulmonary embolism following laparoscopic ovariectomy: a case report.
AB  - Laparoscopic surgery is usually considered to be less invasive when compared to
      traditional laparotomy, and is regarded as a relatively low-risk procedure for
      postoperative complications because of the reduced surgical stress and earlier
      mobilization. However, we describe a 47-year-old woman who presented with acute
      respiratory distress, drowsy consciousness, and circulatory collapse shortly
      after gynecologic laparoscopic ovariectomy for removing an ovarian teratoma at a
      local hospital. After resuscitation, the patient was transferred to our emergency
      department. Immediate bedside electrocardiographic and echocardiographic
      examination results led to acute pulmonary embolism being quickly diagnosed. The
      patient received subsequent intensive care with smooth course. Although pulmonary
      embolism is rare after laparoscopic surgery, early detection and quick treatment
      are important in the management of this life-threatening complication and offer
      good prognosis. The risk of pulmonary embolism after gynecologic laparoscopic
      surgery remains unclear. Therefore, the decision to provide prophylaxis is up to
      the individual physician, and should take into consideration the patient's
      individual risk factors and comorbidities.

PMID- 17000447
TI  - Successful localization and surgical removal of ingested sewing needles under
      mini C-arm fluoroscopy: a case report.
AB  - Foreign body ingestion is common, but ingestion of multiple sewing needles is
      rare. Most ingested sharp metallic bodies pass through the digestive tract
      spontaneously and patients can be managed conservatively. Sometimes, however,
      perforation develops and surgical treatment is necessary. It is hard to localize
      ingested sewing needles because they tend to scatter widely in the digestive
      tract and are impalpable manually. We report a psychiatric patient who ingested
      six sewing needles: one intact needle was found at the larynx, one had penetrated
      into the stomach, one was in the duodenum, one was in the cecum, one was broken
      into two pieces, and the final needle was broken into three pieces. All of the
      broken fragments were in the colon. The needle at the larynx was removed by a
      laryngoscope. Subsequently, we used mini C-arm fluoroscopy to localize the
      remaining needles and successfully removed all of them intraoperatively.

PMID- 17000448
TI  - Neurofibroma of the lingual nerve: a case report.
AB  - A neurofibroma of the lingual nerve is a rare clinical finding, the most common
      lesion site of a lingual neurofibroma being the tongue. In most situations, it is
      difficult to determine the precise nerve origins. Herein, we report a case of
      lingual nerve neurofibroma that presented as a submandibular mass, mimicking a
      submandibular gland tumor or solitary lymphadenopathy. Complete surgical excision
      of such a lesion for histopathologic examination provides a better treatment and
      final diagnosis. For a patient presenting with neurofibromatosis and a
      submandibular mass, a neurofibroma of nerve origin should be considered in the
      differential diagnosis.

PMID- 17000449
TI  - Retropharyngeal schwannoma excised through a transoral approach: a case report.
AB  - The contents of the retropharyngeal space are limited to fat and retropharyngeal
      nodes. Primary tumors originating from the retropharyngeal space are rare. More
      than 25% of schwannomas are found in the head and neck region, and they are
      rarely found in the retropharyngeal space. Here, we report the case of a 44-year
      old woman with a schwannoma confined to the left retropharyngeal space, who
      presented with snoring and a mild lump in the throat sensation. Physical
      examination revealed anterior bulging of the left oropharyngeal wall, with intact
      mucosa. Magnetic resonance imaging showed a well-defined, encapsulated tumor in
      the left retropharyngeal space with bright signal intensity on T2-weighted images
      and low signal intensity on T1-weighted images, which was strongly enhanced after
      gadolinium administration. The tumor was removed through a transoral approach,
      resulting in a short postoperative recovery time without complications. The
      pathologic diagnosis was schwannoma. The patient has been well and free of tumor
      recurrence for 2 years. From anatomic and physiologic viewpoints, excision
      through a transoral approach is a good choice for a confined retropharyngeal
      schwannoma.

PMID- 17000450
TI  - Treatment of mandibular prognathism.
AB  - Mandibular prognathism (MP) or skeletal Class III malocclusion with a prognathic
      mandible is one of the most severe maxillofacial deformities. Facial growth
      modification can be an effective method of resolving skeletal Class III jaw
      discrepancies in growing children with dentofacial orthopedic appliances
      including the chincup, face mask, maxillary protraction combined with chincup
      traction and the Frankel functional regulator III appliance. Orthognathic surgery
      in conjunction with orthodontic treatment is required for the correction of adult
      MP. The two most commonly applied surgical procedures to correct MP are sagittal
      split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy. Both
      procedures are suitable for patients in whom a desirable occlusal relationship
      can be obtained with a setback of the mandible, and each has its own advantages
      and disadvantages. In bilateral SSRO, the intentional ostectomy of the posterior
      part of the distal segment can offer long-term positioned stability. This may be
      attributable to reduction of tension in the pterygomasseteric sling that applies
      force in the posterior mandible. While various environmental factors have been
      found to contribute to the development of MP, heredity plays a substantial role.
      The relative contributions of genetic and environmental components in the
      etiology of MP are unclear. The recent identification of the genetic
      susceptibilities to MP constitutes the first step toward understanding the
      molecular pathogenesis of MP. Further studies in molecular biology are needed to
      identify the gene-environment interactions associated with the phenotypic
      diversity of MP and the heterogenic developmental mechanisms thought to be
      responsible for them.

PMID- 17000451
TI  - Comparison of primary wound closure versus open wound management in perforated
      appendicitis.
AB  - BACKGROUND/PURPOSE: Open wound management has long been the most common practice
      after appendectomy for perforated appendicitis. Primary closure, however, has
      recently been advocated to reduce cost and morbidity. The aim of this study was
      to compare the results of open wound management and primary wound closure in
      adult patients (age, > or =15 years) with perforated appendicitis. METHODS:
      Hospital records of 390 patients (age, > or =15 years) who underwent appendectomy
      between January 2002 and December 2004 were reviewed to identify surgical wound
      infection (SWI) and pathologic diagnosis. Perforated appendicitis was the
      indication for appendectomy in 65 of these patients. The incision wounds in these
      65 patients were closed primarily in 41 and left open at the end of the operation
      in 24. The duration of symptoms, white blood cell count, operative time,
      incidence of SWI, length of stay (LOS) and readmission rate were compared between
      patients with these two different methods of wound management. RESULTS: Patients
      whose wounds were closed primarily had a higher incidence of SWI (43.9% vs. 4.2%,
      p < 0.001) and longer LOS (10 days vs. 7.9 days, p = 0.044). The readmission rate
      was also higher for patients whose wounds were closed primarily; however, this
      difference was not significant. CONCLUSION: Open wound management may be
      preferable to primary wound closure for perforated appendicitis in adults because
      of a lower incidence of SWI and a shorter LOS. Randomized clinical trials,
      however, are needed to establish these findings.

PMID- 17000452
TI  - Pilocarpine hydrochloride for the treatment of xerostomia in patients with
      Sjogren's syndrome in Taiwan--a double-blind, placebo-controlled trial.
AB  - BACKGROUND/PURPOSE: Sjogren's syndrome (SS) is characterized by diminished
      exocrine secretions with the resultant symptoms of dry mouth and dry eye. As
      genetic predisposition and ethnicity may alter the effectiveness of drug
      treatment, evaluation of the efficacy and safety of the secretagogue pilocarpine
      hydrochloride in the treatment of xerostomia in patients with SS in different
      populations is needed. METHODS: Forty-four patients with SS were enrolled in this
      double-blind, placebo-controlled trial. Patients were randomized to receive 5 mg
      pilocarpine (Salagen) or placebo tablet four times daily for 12 weeks. Global
      evaluation and subjective responses of patients were assessed by questionnaires
      with visual analog scales and categorical checkboxes. Saliva production was also
      measured by modified Saxon's test. RESULTS: Pilocarpine treatment significantly
      improved global assessment of dry mouth, symptoms associated with dry mouth
      (mouth comfort, ability to sleep and ability to speak), and saliva production
      compared to placebo. The drug was well tolerated and the most common adverse
      effect was sweating (5/23, 21.7%) resulting from the muscarinic agonist action of
      the drug. No serious drug-related adverse effect was found in this study.
      CONCLUSION: The results of this study suggest that therapy with 5 mg pilocarpine
      four times daily is effective, safe and well tolerated for the relief of oral
      symptoms in patients with SS in Taiwan.

PMID- 17000453
TI  - Poor renal outcome of antineutrophil cytoplasmic antibody negative Pauci-immune
      glomerulonephritis in Taiwanese.
AB  - BACKGROUND/PURPOSE: Pauci-immune glomerulonephritis (GN) is an important cause of
      crescentic GN, acute renal failure and mortality. However, data are limited on
      the clinical presentation and outcome in antineutrophil cytoplasmic antibody
      (ANCA) negative patients, especially in Asians. METHODS: This retrospective study
      analyzed medical records and pathology slides of patients who received renal
      biopsy between February 1998 and October 2004. Enzyme-linked immunosorbent assay
      was used routinely for ANCA testing in all patients. RESULTS: Among 637 patients
      with biopsy-proven GN included in this study, 88 (13.8%) had glomerular crescent
      formation. Among them, pauci-immune crescentic glomerulonephritis (PICGN) (42
      patients, 47.2%) and lupus nephritis (25 patients, 28.4%) were the most common
      pathologic diagnoses. Lupus patients were younger (p = 0.028), while PICGN
      patients had more chronic lesions (p < 0.001), extensive glomerular crescents (p
      < 0.001), less severe proteinuria (p < 0.001) and poorer renal survival (p =
      0.0017). Among the PICGN patients, 62.5% had a positive ANCA test, 80% had
      myeloperoxidase-ANCA and 20% had proteinase-3-ANCA. Subgroup analysis showed that
      ANCA negativity was associated with less crescent formation (p < 0.001) but more
      chronic glomerular lesions (p < 0.001) and a trend toward worse renal outcome (p
      = 0.055). CONCLUSION: This study illustrates the necessity for pathologic
      diagnosis of pauci-immune GN despite ANCA negativity. The poor prognosis
      associated with ANCA negativity in this study may be partly due to delayed
      diagnosis since these patients frequently lacked systemic involvement.

PMID- 17000454
TI  - Surgical outcome of aortopulmonary window repair in early infancy.
AB  - BACKGROUND/PURPOSE: Aortopulmonary window (APW) is a rare congenital heart
      disease and surgical correction is advised as early as possible. However, few
      studies have focused on infants. This study sought to define the clinical
      features and outcomes in patients who underwent surgical repair of APW in early
      infancy. METHODS: Between 1983 and 2004, there were 14 patients (0.15%) with APW
      out of 9414 patients with congenital heart disease. Ten underwent surgical repair
      of APW when they were younger than 4 months of age and constituted the study
      population. RESULTS: There were four patients with type I APW, three with type II
      and three with type III. Concomitant cardiovascular anomalies were present in all
      patients, mainly aortic arch anomalies (80%, including right aortic arch,
      interrupted aortic arch [IAA] and severe coarctation of the aorta [CoA]).
      Patients were further grouped according to the presence (n = 5) or absence (n =
      5) of IAA or severe CoA. All patients underwent surgical repair of APW with
      various techniques, including direct ligation, division and patch or flap
      closure. There was one early postoperative death. None of the survivors died
      during a median follow-up of 34 months (range, 8-116 months). Patients with IAA
      or severe CoA had longer intubation time, intensive care unit stay and hospital
      stay. Early reintervention was required only in patients with IAA or severe CoA
      (n = 3, 60%). Among them, two had significant residuals and both had type III
      APW. CONCLUSION: Long-term outcomes are generally good in patients with APW who
      have undergone surgical correction in early infancy. However, associated IAA or
      severe CoA may predict a prolonged hospital course and an increased risk of early
      reintervention. In patients with type III APW requiring early reintervention,
      significant hemodynamic residuals may be common even after reintervention.

PMID- 17000455
TI  - Effects of physician specialty on use of antidiabetes drugs, process and outcomes
      of diabetes care in a medical center.
AB  - BACKGROUND/PURPOSE: Physician characteristics might determine the quality of
      diabetes care. This study evaluated the effects of physician specialty on the use
      of antidiabetes drugs, process and outcomes of diabetes care. METHODS: In 2002,
      12,023 diabetes patients visited outpatient clinics more than four times at
      National Taiwan University Hospital. One-tenth of the patients were randomly
      sampled out. A retrospective chart review was conducted for those who were
      regularly cared for by endocrinologists (EN), other specialists in internal
      medicine (IM) and family medicine (FM) physicians. The use of antidiabetes drugs
      was assessed. Effects of physician specialty on the process or outcome indicators
      were analyzed by logistic or linear regression, accordingly. RESULTS: A total of
      875 diabetes patients (477 men, 398 women) with a mean age of 62.3 +/- 12.7 years
      were recruited. EN patients had the highest rate of being prescribed insulin,
      metformin or nonsulfonylurea insulin secretagogues, and the lowest rate of being
      given sulfonylureas. EN patients showed a significantly better adherence to
      glucose checkup, glycosylated hemoglobin A1C measures and urinalysis than IM
      patients. EN patients also showed better adherence to glucose checkup and
      urinalysis than FM patients. EN patients had the lowest mean fasting plasma
      glucose (FPG) and lowest mean postprandial plasma glucose (PPG). The difference
      in PPG between EN and IM patients and the difference in FPG between EN and FM
      patients were persistently significant following adjustment by patient and
      physician characteristics. CONCLUSION: The use of antidiabetes drugs differed
      among patients cared for by EN, internists or generalists. Physician specialty
      had significant effects on the process and outcomes of diabetes care.

PMID- 17000456
TI  - Relationship between Mandarin speech reception thresholds and pure-tone
      thresholds in the geriatric population.
AB  - BACKGROUND/PURPOSE: In the geriatric population, the reliability of pure-tone
      threshold (PTT) is sometimes poorer than that in young adults because of various
      reasons. This study assessed the relationship between Mandarin speech reception
      thresholds (SRTs) and PTTs in the aged and developed SRT as a measure for
      corroborating PTT. METHODS: This prospective study enrolled 46 consecutive
      subjects over 60 years of age. The results of SRT and PTT were collected from one
      ear randomly selected from each subject. Simple linear and multiple regressions
      were used to determine the correlation and linear regression coefficients between
      SRTs and PTTs at various frequencies. RESULTS: In the simple regression analysis,
      the correlation coefficient was highest at 1000 Hz (r = 0.949) and 500 Hz (r =
      0.922), followed by 250 Hz (r = 0.850) and 2000 Hz (r = 0.792). In the multiple
      regression model with SRT as the dependent variable and PTTs as predictor
      variables, the resultant multiple correlation coefficient R was 0.967, while R2
      was 0.936. In this model, PTTs at the frequencies of 500 Hz and 1000 Hz
      contributed significantly to the variance in SRTs with p values of 0.029 and <
      0.001, respectively. These results demonstrated that the Mandarin SRT is strongly
      associated with PTTs at the frequencies of 500 Hz and 1000 Hz. CONCLUSION: This
      study established the agreement between Mandarin SRTs and PTTs in the low tone
      area of speech frequencies in the geriatric population. In clinical settings, SRT
      test can be rapidly and easily performed and is relatively inexpensive. It is a
      vital indicator of the accuracy of PTT measurement.

PMID- 17000457
TI  - Takotsubo cardiomyopathy--transient left ventricular apical ballooning mimicking
      acute myocardial infarction.
AB  - Takotsubo cardiomyopathy is characterized by transient left ventricular
      dysfunction with clinical symptoms of chest pain, electrocardiographic changes of
      ST-segment elevation or T wave inversion, which mimics acute myocardial
      infarction in patients without angiographically significant coronary artery
      stenosis. We report a 75-year-old woman with a history of chest tightness who
      presented with typical pictures of takotsubo cardiomyopathy. Acute myocardial
      infarction was initially diagnosed based on the electrocardiographic changes and
      elevated troponin. Apical akinesis and ballooning with basal hyperkinesis were
      noted during left ventriculography. Coronary angiography, however, did not show
      significant coronary artery stenosis. Electrocardiography was normal 3 months
      later. Follow-up echocardiography did not show any wall motion abnormality. This
      patient remained well without chest pain or dyspnea over 24 months of follow-up.
      Optimal medical management of takotsubo cardiomyopathy remains unclear. This
      patient received diltiazem to prevent possible coronary artery spasm. The
      prognosis of this syndrome seems to be favorable except for occasional mortality
      due to left ventricular rupture or ventricular arrhythmia. Recurrence of this
      syndrome is rare.

PMID- 17000458
TI  - Late-onset congestive heart failure with multiple carotid-jugular fistulae and
      pseudoaneurysm after penetration injury.
AB  - Trauma-acquired multiple arteriovenous fistulae with late-onset congestive heart
      failure has not been documented. We describe a 29-year-old man who presented with
      progressive congestive heart failure 25 years after a penetrating trauma to the
      left side of the neck. The neck duplex showed a large shunt between the carotid
      artery and internal jugular vein. Arteriography showed three high-flow
      arteriovenous fistulae between these two vessels. Magnetic resonance angiography
      (MRA) showed a carotid pseudoaneurysm originating from three different loci of
      the carotid artery with a large aneurysm-venous communication between the
      pseudoaneurysm and the internal jugular vein. Reconstruction of contrast MRA
      showed three different arteriovenous fistulae, leading to the decision to perform
      aneurysmectomy, carotid artery repair and jugular vein patch angioplasty. The
      favorable outcome of this case illustrates that surgery is a reasonable
      alternative when an endovascular approach is not feasible in patients with trauma
      acquired arteriovenous fistulae.

PMID- 17000459
TI  - Thrombolytic therapy in acute cerebral infarction complicating diagnostic cardiac
      catheterization.
AB  - Diagnostic and interventional percutaneous coronary catheterization is associated
      with stroke. Many of such strokes are asymptomatic, but some are devastating.
      Once the diagnosis of acute cerebral infarction is confirmed, thrombolytic
      therapy should be administrated within the time window of 3 hours. We report a 61
      year-old woman who suffered from an acute cerebral infarction during diagnostic
      cardiac catheterization for unstable angina, which manifested as sudden onset of
      global aphasia, right hemiplegia and gaze preponderance to the left side.
      Computed tomography of the head performed immediately after recognition of the
      symptoms showed a hyperdense middle cerebral artery (MCA) sign. Following prompt
      recognition and diagnosis, intravenous thrombolytic therapy was administered 2
      hours after symptom onset. The patient had a favorable outcome. Initially,
      National Institutes of Health Stroke Scale score was 21, and 24 hours later it
      improved to 9. The hyperdense MCA lesion had resolved on the 24-hour follow-up
      scan. This case illustrates the clinical benefit of thrombolytic therapy in the
      setting of acute stroke associated with cardiac catheterization.

PMID- 17000460
TI  - Homozygous SLC25A13 mutation in a Taiwanese patient with adult-onset
      citrullinemia complicated with steatosis and hepatocellular carcinoma.
AB  - Citrullinemia is a metabolic disorder characterized by elevated plasma
      concentrations of citrulline and ammonia. Adult-onset citrullinemia (type II,
      CTLN2) has been attributed to citrin deficiency caused by mutations in the
      SLC25A13 gene. CTLN2 is associated with a high incidence of hepatocellular
      carcinoma (HCC) in Japanese. We report a 48-year-old Taiwanese man with
      citrullinemia, who was in good health until the age of 34 when he had repeated
      episodes of consciousness disturbance. Hyperammonia (201 micromol/L) was found
      during an episode of coma. Liver function and electrolyte levels were normal at
      that time. Serologic markers of viral hepatitis B and C were negative. Analysis
      of genomic DNA extracted from peripheral blood leukocytes showed homozygous
      851del4 mutation in exon 9 of the SLC25A13 gene on chromosome 7q21.3. Fourteen
      years after disease onset, at the age of 48, he was admitted due to an episode of
      coma. Abdominal sonography and computed tomography showed a 2.5 cm tumor in the
      left lobe of the liver, without evidence of liver cirrhosis. Wedge resection of
      the tumor was performed and grade 2 HCC was diagnosed. The nontumor part of the
      resected specimen showed chronic persistent hepatitis with moderate steatosis.
      The results in this case support that both citrin deficiency and steatohepatitis
      may contribute to hepatocarcinogenesis.

PMID- 17000461
TI  - Fatal Klebsiella pneumoniae meningitis and emphysematous brain abscess after
      endoscopic variceal ligation in a patient with liver cirrhosis and diabetes
      mellitus.
AB  - Procedure-related bacterial infections may complicate esophageal variceal
      ligation in cirrhosis patients. Here, we report a 58-year-old man with underlying
      diabetes and liver cirrhosis who developed Klebsiella pneumoniae meningitis and
      brain abscess with gas formation in brain parenchyma and ventricles after this
      procedure. Despite administration of appropriate antimicrobial therapy, he became
      comatose on the 3rd day of acute illness and died on the 4th day of
      hospitalization. This case highlights the indication for antimicrobial
      prophylaxis in cirrhotic patients with gastrointestinal bleeding, and the need
      for early and heightened awareness of central nervous system infections in
      cirrhotic patients with hepatic encephalopathy.

PMID- 17000462
TI  - Isolated hand weakness in cortical infarctions.
AB  - Isolated hand weakness due to stroke is infrequently observed, and often
      misdiagnosed as peripheral lesions. This study investigated the clinical and
      radiologic profiles in such patients. Five men and one woman were studied. All
      patients underwent cranial magnetic resonance imaging (MRI) to confirm the
      diagnosis. Four patients had uniform weakness and the other two had either
      differential radial or ulnar weakness, respectively. MRI showed acute infarctions
      involving the hand knob area of the primary motor cortex (M1) in five patients
      and the postcentral gyrus sparing the precentral gyrus in one patient. Two
      patients with uniform digit weakness had additional involvement of the inferior
      parietal lobule. These findings suggest that isolated or predominant hand
      weakness in patients with cerebral infarctions is not necessarily caused by
      lesions in the M1 knob area, and that the control center of hand movement is not
      limited to the knob area alone.

PMID- 17000463
TI  - Ecstasy poisoning in a toddler.

PMID- 17000465
TI  - The neurotoxin, MPP+, induces hyperphosphorylation of Tau, in the presence of
      alpha-Synuclein, in SH-SY5Y neuroblastoma cells.
AB  - Alzheimer's disease (AD) is characterized, in part, by intracellular
      neurofibrillary tangles composed of hyperphosphorylated filamentous aggregates of
      the microtubule-associated protein, Tau. Such hyperphosphorylated Tau is also
      found in Lewy bodies (LBs), and cytoplasmic inclusion bodies in certain forms of
      Parkinson's disease (PD). Further, LBs also contain aggregates of alpha-synuclein
      (alpha-Syn), also a microtubule-associated protein, which has been linked to the
      genesis of PD. To investigate a specific correlation between Tau phosphorylation
      and alpha-Syn, we generated a SH-SY5Y cell line that stably expresses human wild
      type alpha-Syn. Protein expression levels in the stably transfected cell line
      (SHalpha-Syn) were within the physiological range of alpha-Syn expression found
      in Substantia nigra. We show here, in the MPP+ (1-methyl-4-phenylpyridinium ion)
      cell model of parkinsonism, a time- and dose-dependent increase in the
      hyperphosphorylation of Tau at pSer396/404 (PHF-1-reactive Tau, p-Tau),
      concomitant with increased accumulation of alpha-Syn, upon treatment of cells
      with the neurotoxin. This increase in p-Tau was strictly dependent on the
      presence of alphaSyn, since in transfected cells not expressing any alpha-Syn,
      MPP+ failed to induce an increase in PHF-1-reactive Tau. The production of p-Tau
      caused increased cytotoxicity as indexed by reduced cell viability. Moreover, in
      the absence of alpha-Syn, the cells were more resistant to MPP+ -induced cell
      death. The increased levels of both p-Tau and alpha-Syn led to diminished levels
      of these proteins associated with the cytoskeleton, which was accompanied by
      enhanced presence of the proteins in the cytoskeletal-free fractions. These data
      indicate that alpha-Syn and p-Tau modulate the pathogenicity of one another,
      suggesting a novel convergent mechanism of neurodegeneration.

PMID- 17000466
TI  - Neurochemical and behavioural characterisation of alkoxyamphetamine derivatives
      in rats.
AB  - The clinical utility of amphetamine and amphetamine analogues has been
      jeopardized by a number of side effects and toxicity, partly due to complex
      mechanisms of action. While some of the analogues have been individually
      characterised, there is still need for comparative studies, in particularly on
      their efficacy to release dopamine and 5-hydroxytryptamine, further enlightening
      some of the synaptic mechanisms conveying their actions. Thus, we have compared
      four alkoxyamphetamine derivatives, i.e., p-methoxyamphetamine; p
      methoxymethamphetamine; methylenedioxyamphetamine, methylenedioxymethamphetamine,
      using methamphetamine, and D-amphetamine, as reference substances, on rotational
      behaviour and releasing mechanisms studied with in vivo microdialysis in rats.
      All alkoxylated-derivatives produced a long-lasting rotational behaviour at 10
      mg/kg s.c., but the reference substances produced a strong rotation already at 2
      mg/kg s.c. in 6-hydroxydopamine-lesioned rats. At the concentration of 100
      micromolar, the alkoxylated-derivatives were equipotent to evoke dopamine and 5
      hydroxytryptamine release in rat neostriatum, while D-amphetamine and
      methamphetamine were more efficient on dopamine release. Pre-treatment with
      methamphetamine or the alkoxylated-derivatives produced a remarkable decrease of
      the effect of K+ -depolarisation on both dopamine and 5-hydroxytryptamine
      release. The insertion of a methoxy or a methylenedioxy group on the benzene ring
      of D-amphetamine or methamphetamine, or N-methylation of the D-amphetamine
      molecule alters the selectivity of the compounds. The efficacy of the alkoxylated
      derivatives on dopamine and 5-hydroxytryptamine release was similar, but
      stimulated less dopamine release and produced less rotational behaviour than D
      amphetamine and methamphetamine. The lower efficacy of K+ -depolarisation
      following pre-treatments with the derivatives suggests an impairment of
      releasable monoamine stores. The present observations can enlighten the
      mechanisms of action of drugs showing a high risk for abuse among young
      populations.

PMID- 17000467
TI  - EGCG protects HT-22 cells against glutamate-induced oxidative stress.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. Many
      health promoting effects of EGCG have been reported based on its antioxidative
      and gene modulation properties, but no study has demonstrated a protective effect
      of EGCG against glutamate-induced neuronal damage. Excessive glutamate
      stimulation on neuronal cells leads to accumulation of reactive oxygen species
      (ROS) which ultimately contribute to cell death in stroke, trauma and other
      neurodegenerative disorders. In this study, mouse hippocampal cell line, HT-22,
      was used to determine the effect of EGCG on glutamate neurotoxicity. It was found
      that EGCG protected HT-22 cells against glutamate neurotoxicity when administered
      10 h after glutamate incubation. The protective action of EGCG is mainly due to
      its antioxidative effect.

PMID- 17000468
TI  - Dopamine D2 agonists, bromocriptine and quinpirole, increase MPP+ -induced
      toxicity in PC12 cells.
AB  - Dopaminergic cell loss in the mesencephalic substantia nigra is the hallmark of
      Parkinson's disease and may be associated with abnormal oxidative metabolic
      activity. However, the delicate balance underlying dopamine decline and oxidative
      stress is still a matter of debate. The aim of this study was to analyze the
      possible modulation of D2 agonists and antagonists on MPP+ (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridinium ion) -induced cellular death in differentiated and
      undifferentiated PC12 cells. Using colorimetric assays, western blots and reverse
      transcriptase-PCR, we demonstrated that two D2 agonists, bromocriptine and
      quinpirole, consistently increased MPP+ -induced cytotoxicity in both
      differentiated and undifferentiated PC12 cells, whereas D2 antagonists do not
      modulate cell death. However, this increase in cellular death was reversed when
      bromocriptine or quinpirole were used in presence of D2 antagonists. On the other
      hand, 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine (GBR
      12909), a potent inhibitor of the dopamine transporter, partially reversed MPP+ 
      induced cellular death and completely abolished the increase of cellular death
      induced by bromocriptine. Dopamine agonists and antagonists also modulate the
      expression of the dopamine transporter in PC12 cells; in particular,
      bromocriptine may alter MPP+ uptake by increasing DAT expression We also show
      that, in our cellular paradigm, D2 receptor mRNA levels are more abundant that D3
      mRNA levels and MPP+ and /or bromocriptine could not modulate D2 gene expression
      while D3 gene expression clearly decrease after MPP+ and /or bromocriptine
      treatment.

PMID- 17000469
TI  - Overexpression of GRK2 in Alzheimer disease and in a chronic hypoperfusion rat
      model is an early marker of brain mitochondrial lesions.
AB  - Heterotrimeric guanine nucleotide-binding (G) protein-coupled receptor kinases
      (GRKs) are cytosolic proteins that are known to contribute to the adaptation of
      the heptahelical G protein-coupled receptors (GPCRs) and to regulate downstream
      signals through these receptors. GPCRs mediate the action of messengers that are
      key modulators of cardiac and vascular cell function, such as growth and
      differentiation. GRKs are members of a multigene family, which are classified
      into three subfamilies and are found in cardiac, vascular and cerebral tissues.
      Increasing evidence strongly supports the hypothesis that vascular damage is an
      early contributor to the development of Alzheimer disease (AD) and/or other
      pathology that can mimic human AD. Based on this hypothesis, and since kinases of
      this family are known to regulate numerous receptor functions both in the brain,
      myocardium and elsewhere, we explored cellular and subcellular localization by
      immunoreactivity of G protein-coupled receptor kinase 2 (GRK2), also known as
      beta-adrenergic receptor kinase-1(betaARK1), in the early pathogenesis of AD and
      in ischemia reperfusion injury models of brain hypoperfusion. In the present
      study, we used the two-vessel carotid artery occlusion model, namely the 2-VO
      system that results in chronic brain hypoperfusion (CBH) and mimics mild
      cognitive impairment (MCI) and vascular changes in AD pathology. Our findings
      demonstrate the early overexpression of GRK2 member kinase in the
      cerebrovasculature, especially endothelial cells (EC) following CBH, as well as
      in select cells from human AD tissue. We found a significant increase in GRK2
      immunoreactivity in the EC of AD patients and after CBH, which preceded any
      amyloid deposition. Since GRK2 activity is associated with certain compensatory
      changes in brain cellular compartments and in ischemic cardiac tissue, our
      findings suggest that chronic hypoperfusion initiates oxidative stress in these
      conditions and appears to be the main initiating injury stimulus for disruption
      of brain and cerebrovascular homeostasis and metabolism.

PMID- 17000470
TI  - A prospective assessment of porphyrins in autistic disorders: a potential marker
      for heavy metal exposure.
AB  - Autism was recently associated with a urinary porphyrin pattern indicative of
      mercury toxicity in a large cohort of French children. The IRB of the Institute
      for Chronic Illnesses approved the present study. A total of 37 consecutive
      American patients (> or = 7 years-old) with autism spectrum disorders (ASDs)
      (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-DSM IV),
      born from 1983-1998, that presented to the Genetic Centers of America for
      outpatient genetic evaluations were prospectively examined for urinary prophryin
      levels (LabCorp, Inc.) from June 2005-June 2006. Imaging and laboratory testing
      were conducted on each patient to rule-out other causal factors for their ASDs.
      As controls, age-, sex-, and race-matched neurotypical ASD siblings were
      examined. An apparent dose-response effect was observed between autism severity
      and increased urinary coproporphyrins. Patients with non-chelated autism (2.25
      fold, 83% had levels > 2 SD above the control mean) and non-chelated ASDs (2
      fold, 58% had levels > 2 SD above the control mean), but not patients with non
      chelated pervasive developmental delay-not otherwise specified (PDD-NOS) or
      Asperger's disorder (1.4-fold, 46% had levels > 2 SD above the control mean), had
      significantly increased median coproporphyrin levels versus controls. A
      significant increase (1.7-fold) in median coproporphyrin levels was observed
      among non-chelated ASD patients versus chelated ASD patients. Porphyrins should
      be routinely clinically measured in ASDs, and potential ASD treatments should
      consider monitoring porphyrin levels. Additional research should be conducted to
      evaluate the potential role for mercury exposure in some ASDs.

PMID- 17000472
TI  - Improving teamwork climate in operating theatres: the shift from
      multiprofessionalismto interprofessionalism.
AB  - A multi-faceted, longitudinal and prospective collaborative inquiry was initiated
      in December 2002 with one half of the cohort of operating theatre personnel in a
      large, acute UK hospital serving a mainly rural population. The same intervention
      was introduced in January 2004 to the other half of the cohort. The project aims
      to improve patient safety through a structured educational intervention focussed
      upon changing teamwork practices. This article reports one critical element of
      the larger project - changing teamwork climate as a necessary precursor to
      establishing an interprofessional teamwork culture. The aggregate of individual,
      unidirectional attitude changes across a large cohort constitutes a change in
      climate. This shift challenges the conventional culture of multiprofessionalism,
      where uniprofessional identification (the "silo" mentality) is traditionally
      strong.

PMID- 17000473
TI  - Towards safer interprofessional communication: constructing a model of "utility"
      from preoperative team briefings.
AB  - "Improved team communication" is broadly advocated in the discourse on safety but
      rarely supported by a precise understanding of the relationship between specific
      communication practices and concrete improvements in collaborative work
      processes. We sought to improve such understanding by analyzing the discourse
      arising from structured preoperative team briefings among surgeons, nurses, and
      anesthesiologists prior to general surgery procedures. Analysis of observers'
      fieldnotes from 302 briefings yielded a two-part model of communicative
      "utility", defined as the visible impact of communication on team awareness and
      behavior. "Informational utility" occurred when team awareness or knowledge was
      improved by provision of new information, explicit confirmation, reminders, or
      education. "Functional utility" represented direct communication - work
      connections: many briefings identified problems, prompting decision-making and
      follow-up actions. The crux of the model is an elaboration of the causal pathway
      between a specific communication practice (the team briefing), intermediary
      processes such as enhanced knowledge and purposeful action, and the quality and
      safety of collaborative care processes. Modeling this pathway is a critical step
      in promoting change, as it renders visible both the latent dangers present in
      current team communication systems and the specific ways in which altered
      communication patterns can impact team awareness and behaviors.

PMID- 17000474
TI  - The complexity of measuring interprofessional teamwork in the operating theatre.
AB  - Surgery depends on interprofessional teamwork, which is becoming increasingly
      specialized. If surgery is to become a highly reliable system, it must adapt and
      professionals must learn from, and share, tested models of interprofessional
      teamwork. Trainers also need valid measures of teamwork to assess individual and
      team performance. However, measurement and assessment of interprofessional
      teamwork is lacking and interprofessional team training is scarce in the surgical
      domain. This paper addresses the complexity of measuring interprofessional
      teamwork in the operating theatre. It focuses mainly on the design and properties
      of observational assessment tools. The report and analysis serves to inform the
      researcher or clinician of the issues to consider when designing or choosing from
      alternative measures of team performance for training or assessment.

PMID- 17000475
TI  - Educating interprofessional learners for quality, safety and systems improvement.
AB  - Most health professionals in training, as well as those in practice, lack the
      knowledge and skills they need to play an effective role in systems improvement.
      Until very recently, these competencies were not included in formal (or informal)
      educational curricula. Interprofessional collaboration - another core competency
      needed for successful systems improvement - is also inadequately taught and
      learned. Achieving Competence Today (ACT) was designed as a new model for
      interprofessional education for quality, safety and health systems improvement.
      The core of ACT is a four-module active learning course during which learners
      from different disciplines work together to develop a Quality Improvement Project
      to address a quality or safety problem in their own practice system. In this
      paper we describe the ACT program and curriculum model, discuss our strategies
      for maximizing ACT's interprofessional potential, and make recommendations for
      the future.

PMID- 17000476
TI  - Improving patient safety by using interprofessional simulation training in health
      professional education.
AB  - Modern medicine is complex. Reports and surveys demonstrate that patient safety
      is a major problem. Health educators focus on professional knowledge and less on
      how to improve patient care and safety. The ability to act as part of a team,
      fostering communication, co-operation and leadership is seldom found in health
      education. This paper reports the findings from pilot testing a simulated
      training program in interprofessional student teams. Four teams each comprising
      one medical, nursing, and intensive nursing student (n = 12), were exposed to two
      simulation scenarios twice. Focus groups were used to evaluate the program. The
      findings suggest that the students were satisfied with the program, but some of
      the videos and simulation exercises could be more realistic and more in
      accordance with each other. Generally they wanted more interprofessional team
      training, and had learned a lot about their own team performance, personal
      reactions and lack of certain competencies. Involving students in
      interprofessional team training seem to be more likely to enhance their learning
      process. The students' struggles with roles, competence and team skills underline
      the need for more focus on combining professional knowledge learning with team
      training.

PMID- 17000477
TI  - Bridging the "system's" gap between interprofessional care and patient safety:
      sociological insights.
AB  - This paper is based on the premise that a systemic approach is the crucial link
      between patient safety and interprofessional care. It is argued that there has
      been little concern with regard to the need for a critical assessment and
      development of a systems' theoretical model able to envisage the broad approach
      of delivery of health care that patient safety initiatives require. Based on a
      medical sociology approach, the paper analyzes four forces that threaten a well
      sustained development of research and problem-solving strategic proposals that
      are to be derived from the intersection of patient safety and interprofessional
      care, namely: (i) the absence of explicit theoretical models in empirical
      research work in both fields; (ii) the a-critical acceptance of an ideologically
      limited biomedical paradigm in the actual systemic definitions of the clinical
      model; (iii) a fragmentation of the underlying system concept that is unable to
      include all of the actors of the system; and, (iv) the need to go beyond the non
      maleficence principle and include the remaining three bioethical principles in
      medical care. The paper concludes with the proposal of developing theoretically
      grounded empirical interprofessional research that allows the crucial inclusion
      of social sciences in the systemic approach.

PMID- 17000478
TI  - Can the patient be on our team? An operational approach to patient involvement in
      interprofessional approaches to safe care.
AB  - This discussion paper brings together the concept of patient-centred practice
      with interprofessional working and the spectrum of preventive and restorative
      approaches to patient safety. I explore what might be involved in putting
      patients at the heart of a team-based approach to the prevention and management
      of potential clinical errors in their own care; and use the current literature to
      explore areas where interprofessional practice-based interventions may help to
      improve quality of care in ways that can prevent or minimize patient risk. I
      argue that involving patients in safety issues will only happen when staff are
      motivated by real rather than hypothetical needs, and will largely involve
      actions taken at an interpersonal level during routine health care. The paper
      describes a spectrum of practical approaches that can be implemented by teams and
      organizations, ranging from whole population prevention strategies to the
      learning that can be gained from avoidable deaths. It explores concrete examples
      of the ways in which individual patients might be included in a team approach to
      self protection, and addresses underpinning principles of effective
      interprofessional working which are needed to make such approaches effective.

PMID- 17000479
TI  - Domestic violence fatality review teams: an interprofessional model to reduce
      deaths.
AB  - In an effort to reduce injuries and prevent deaths from violence,
      interprofessional domestic violence fatality review teams (DVFRT) have developed
      across the United States and globally to study factors that contribute to
      intimate partner injury and deaths. Drawing upon knowledge from the disciplines
      of health, education, criminal justice, social services, and policy, these teams
      review and analyze domestic violence homicide cases to uncover basic knowledge
      about causes, factors that increase or decrease the risk for death and injury,
      and specific ways to prevent further injury and death. Through interprofessional
      collective recommendations and cooperative actions, these teams are developing
      promising practices and systems' changes that offer better services, learning,
      and interventions to reduce injury and death from domestic violence.

PMID- 17000480
TI  - Reflections on safety and interprofessional care: some conceptual approaches.

PMID- 17000481
TI  - From one to many.

PMID- 17000482
TI  - MOSES: Multidisciplinary Obstetric Simulated Emergency Scenarios.

PMID- 17000483
TI  - Educating for healthcare quality improvement in an interprofessional learning
      environment: a New Zealand initiative.

PMID- 17000484
TI  - An interprofessional medication risk assessment program.

PMID- 17000485
TI  - Using a simulated chaotic home environment for preparing nursing and social work
      students for interdisciplinary care delivery in a Scottish context.

PMID- 17000490
TI  - The Term Breech Trial: are the clinical guidelines justified by the evidence?

PMID- 17000491
TI  - Loss of libido in postmenopausal women.

PMID- 17000492
TI  - Systematic reviews of qualitative evidence: what are the experiences of women
      with endometriosis?
AB  - Just as systematic reviews of quantitative research have developed over the last
      two decades, the use of a systematic review is also superseding narrative non
      systematic reviews in qualitative research in an attempt to bring rigour to
      reviewing research evidence. Qualitative research is concerned with the
      subjective world and the way in which people interpret and make sense of the
      reality of their lives. This paper describes procedures for conducting a
      systematic review on qualitative research, and the methods for assessing the
      quality of qualitative research papers, using published qualitative research on
      endometriosis as an example to demonstrate these. The conclusion from the
      systematic review carried out is that the values and methods utilised for a
      systematic review can usefully be applied to qualitative research. The review of
      endometriosis research revealed that despite the impact of endometriosis on the
      lives of women sufferers, little qualitative research has been conducted, and
      much of that which exists lacks rigour in a number of key areas.

PMID- 17000493
TI  - How competent are obstetric and gynaecology trainees in managing maternal cardiac
      arrests?
AB  - The recent Confidential Enquiry (2000-2002) has emphasised 'emergency drills for
      maternal resuscitation should be regularly practised in clinical areas in all
      maternity units'. It was therefore planned to assess the knowledge of airway
      management and ventilation among obstetrics and gynaecology trainees in the
      Yorkshire Deanery (Training Region). Questionnaires were given to trainees
      attending the Modular Training Programme and were collected on the same day. A
      total of 71 questionnaires were collected which represents 62% of the 113
      trainees in Yorkshire region. Replies were received from 39 registrars, 27 Senior
      House Officers (SHO), four Senior SHOs (SSHO) and one clinical fellow. MRCOG Part
      1 was passed by 52% and 36% of trainees had MRCOG Part 2. A total of 69% of
      trainees did not know that chin lift opens the airway in some 70 - 80% of
      patients; 50% of trainees were not aware why jaw thrust is preferred over chin
      lift; 76% of the trainees knew the most common cause of airway obstruction in a
      patient with an altered level of consciousness--the tongue falls back and
      obstructs the pharynx ('swallowing the tongue'). Knowledge of the main cause of
      airway obstruction was good among obstetrics and gynaecology trainees, but their
      understanding of how to manage this was found to be relatively poor. Attendance
      at a local Basic Life Support course should be compulsory for obstetric and
      gynaecology trainees early in their career.

PMID- 17000494
TI  - Scuba diving and pregnancy: can we determine safe limits?
AB  - No human data, investigating the effects on the fetus of diving, have been
      published since 1989. We investigated any potential link between diving while
      pregnant and fetal abnormalities by evaluating field data from retrospective
      study No.1 (1990/2) and prospective study No.2 (1996/2000). Some 129 women
      reported 157 pregnancies over 1,465 dives. Latest gestational age reported while
      diving was 35 weeks. One respondent reported 92 dives during a single pregnancy,
      with two dives to 65 m in the 1st trimester. In study No.2 >90% of women ceased
      diving in the 1st trimester, compared with 65% in the earlier study. Overall, the
      women did not conduct enough dives per pregnancy, therefore no significant
      correlation between diving and fetal abnormalities could be established. These
      data indicate women are increasingly observing the diving industry recommendation
      and refraining from diving while pregnant. Field studies are not likely to be
      useful, or the way forward, for future diving and pregnancy research. Differences
      in placental circulation between humans and other animals limit the applicability
      of animal research for pregnancy and diving studies. It is unlikely that the
      effect of scuba diving on the unborn human fetus will be established.

PMID- 17000495
TI  - A comparative study of pregnant women attending a tertiary obstetric unit and a
      district general hospital with a previous history of postnatal depression.
AB  - The aim of this study was to compare pregnant women with a previous history of
      postnatal depression, attending a Tertiary Obstetric Unit in Belfast and a
      District General Hospital in Newry. Women with a previous history of postnatal
      depression recorded at booking for their most current pregnancy were studied
      between January 2001 and May 2002. A total of 443 women (6.6%) in Belfast had a
      history of postnatal depression, compared with 113 women (6%) in Newry. The most
      common age range was 31 - 35 years in both centres. Some 69% of women in Belfast
      compared with 81% of women in Newry were given treatment. Fluoxetine was the
      commonly prescribed drug for each centre. During this subsequent pregnancy, 19
      women (4.3%) in Belfast and five women (4.4%) in Newry remained on
      antidepressants. There was one woman in each centre who took an overdose during
      this pregnancy. More women in Newry were given treatment. During the subsequent
      pregnancy, the percentages of women from each unit requiring antidepressant
      therapy were similar.

PMID- 17000496
TI  - Incidence of and factors associated with meconium staining of the amniotic fluid
      in a Nigerian University Teaching Hospital.
AB  - This study was conducted to determine the incidence of meconium staining of the
      amniotic fluid (MSAF) and its associated factors in a Nigerian teaching hospital.
      Perinatal data on 80 consecutive live, singleton infants of booked mothers born
      through meconium-stained liquor from March - June 2003 were analysed and compared
      with babies born through clear liquor. The incidence of MSAF was 20.4% for 393
      deliveries. The rate increased with gestational age: no case was found below 37
      weeks (p = 0.001). Primiparity, prolonged rupture of fetal membranes and
      obstructed labour were more often associated with MSAF (p = 0.005, p = 0.0013 and
      p = 0.0000002, respectively) as were tachycardia or bradycardia and low Apgar
      scores (p = 0.0000001 and p = 0.046, respectively). It is concluded that meconium
      staining is common. It is related to gestational maturity and stressful
      peripartum conditions and associated with adverse symptomatology in the fetus and
      newborn.

PMID- 17000497
TI  - Comparison between subjective and objective assessments of the cervix before
      induction of labour.
AB  - The aim of the study was to compare the pre-induction cervical assessment by
      Bishop's score with the transvaginal ultrasound cervical length as predictors of
      the induction-delivery interval (IDI) and the success of induction. This
      prospective study included 104 women with singleton pregnancies who were booked
      for induction of labour at term over a period of 3 years. Transvaginal ultrasound
      measurement of the cervical length and Bishop's Score were performed by different
      operators. Data were collected on parity, gestational age, methods of induction,
      Bishop's score, ultrasound cervical length measurements, IDI and mode of
      delivery. A total of 87 women (83.7%) delivered vaginally and 17 (16.3%)
      delivered by caesarean section. Linear regression models demonstrated that
      ultrasound cervical length was a better indicator of IDI than Bishop's score. The
      adjusted R2 for the regression including ultrasound cervical length was 0.87
      compared with a value of 0.67 for the model including Bishop's score. Although
      logistic regression analysis confirmed that cervical effacement was the best
      component of Bishop's score to predict the mode of delivery, ultrasound cervical
      length assessment provided better prediction. Receiver operating characteristic
      curve showed that the optimised cut-off value for prediction of vaginal delivery
      was < or =3.4 cm for the cervical length and >5 for the Bishop's score. At those
      optimised cut-off values the cervical length predicted vaginal delivery with
      sensitivity of 62.1% (95% CI [51%, 72.3%]) and specificity of 100% (95% CI
      [80.5%, 100%]) while the Bishop's score predicted vaginal delivery with a
      sensitivity of 23% (95% CI [14.6%, 33.2%]) and specificity of 88.2% (95% CI
      [63.5%, 98.5%]). Further analysis showed that ultrasound cervical length has a
      higher sensitivity in prediction of vaginal delivery in multiparous than
      nulliparous women (85.1% compared with 35%) at a cut-off value of < or =3.4 cm.
      On the other hand, it has a higher sensitivity in nulliparous comparable with
      multiparous women (85.3% compared with 30%) in prediction of IDI at a cut-off
      value of >3.5 cm. In conclusion, transvaginal ultrasound cervical length
      assessment is better than Bishop's score in predicting the IDI and the success of
      induction of labour.

PMID- 17000498
TI  - A comparison of complications of pregnancy and delivery in morbidly obese and non
      obese women.
AB  - Morbid obesity in pregnancy is a growing problem and is having an impact on
      morbidity, mortality as well as significantly increasing antenatal and intra
      partum costs of pregnancy care. The incidence of morbid obesity in pregnancy in
      our unit was 7.5% during the study period and this was associated with
      statistically significant increased maternal and perinatal morbidity. It also led
      to increased costs because of multidisciplinary management of the pregnancies,
      increased investigations and hospital stay when compared with normal weight
      pregnant women. Looking after morbidly obese pregnant women is an expensive
      undertaking, as the cost of the care of one morbidly obese pregnant woman and her
      baby is several times that of the normal weight woman. Health planners need to
      factor in these costs which are set to escalate given the predicted increase in
      the obese population in the UK.

PMID- 17000499
TI  - Perinatal outcome with HELLP/partial HELLP complicating hypertensive disorders of
      pregnancy. An Indian rural experience.
AB  - A total of 615 women with hypertensive disorders during pregnancy were the study
      subjects. Of these, 145 (23.58%) women had HELLP or partial HELLP (only one or
      two of the three components H,EL, LP). Overall, eight (1.3%), i.e. five out of
      399 primigravida (1.2%) and three of the 216 multigravida (1.3%), had complete
      HELLP and the remaining 137 (22.2%) had partial HELLP. Of the 399 primigravida
      with hypertensive disorders, 107 (26.5%) had partial HELLP, statistically
      significantly more (p<0.002) than the 30 out of the 216 (13.8%) multigravida. In
      210 (44.6%) out of 470 women with hypertension without HELLP/partial HELLP,
      labour was induced and the perinatal mortality rate (PMR) was 138.9 (58.06 in
      term and 363.63 in pre-term cases), and in the other 260 women in whom labour was
      not induced, PMR was 96.15 (in term cases 74.07 and in pre-term 120). Among the
      women with HELLP/partial HELLP (145), out of the 64 women in whom labour was
      induced, the PMR was 359.37 (235.29 in term and 500 in pre-term) and of those in
      whom labour was not induced (81), PMR was 209.87 (106 in term cases and 352.94 in
      pre-term). All the eight women with the full HELLP syndrome had labour induced,
      the PMR in these cases was 500. Overall, in women with HELLP/partial HELLP, the
      PMR was 275.8 and in the remainder with hypertensive disorders without
      HELLP/partial HELLP, it was 114.89.

PMID- 17000500
TI  - Labour management: an appraisal of the role of false labour and latent phase on
      the delivery mode.
AB  - Achieving normal vaginal delivery requires an orderly transition from early
      labour to an established active labour. We analysed retrospectively the outcome
      of labour and the delivery mode based on the diagnosis of labour from the first
      examination of 3,130 parturients. A total of 1,847 (59.1%) delivered mothers had
      the first vaginal examination performed by the senior house officer (SHO). The
      majority (74.4%) of the mothers presented in established labour (cervical
      dilatation > or =4 cm), 25.6% in early labour, while 11.3% in latent phase.
      Patients who presented in established labour had a statistically significant
      higher spontaneous vertex delivery (SVD) rate (Pearson chi2 = 29.74, p = 0.000).
      A total of 62 parturients (17.5%) who presented in the latent phase and 204
      (29.1%) in early labour had an unfavourable delivery mode; 46 had a caesarean
      section. There was a significant correlation between delivery mode and prolonged
      latent phase (Pearson correlation coefficient R = -0.066, p = 0.000). Linear
      regression analysis showed that the total number of VEs was the most significant
      predictor of the delivery mode of SVD (Regression beta-coefficient = 0.278, t =
      10.37, p = 0.000). Early admissions in labour and a prolonged (abnormal) latent
      phase are significant predictors of difficult mode of delivery (poor labour
      outcome). We suggest that the first vaginal examination should be undertaken by
      the most experienced medical personal present at admission.

PMID- 17000501
TI  - Knowledge and use of the partograph among healthcare personnel at the peripheral
      maternity centres in Nigeria.
AB  - In an attempt to evaluate the contributory factors to the high frequency of
      referred cases in obstructed labour at the State's referral hospital, a
      questionnaire-based survey of 396 maternity care-providers from 66 randomly
      selected peripheral delivery units in Ogun State, Nigeria was conducted over a 2
      month period, to evaluate their knowledge and use of the partograph. The majority
      of the personnel were nurses/midwives (45.5%) and community health extension
      workers (CHEW) (42.7%). Of the 216 personnel (54.5%) who were aware of the
      partograph, 36 (16.7%), 119 (55.5%) and 61 (28.2%) demonstrated poor, fair and
      good levels of knowledge, respectively. No junior CHEW had a satisfactory
      knowledge of the partograph. Only 39 (9.8%) of all the personnel routinely
      employed the partograph for labour management and almost half of these
      individuals had a poor level of knowledge. Efforts to limit the frequency of
      referred cases of established obstructed labour to the State's referral hospital
      should include training of care-providers at the peripheral delivery units,
      especially junior personnel in the effective use of the partograph, in addition
      to employing quality assurance measures to check inappropriate use.

PMID- 17000502
TI  - Maternal mortality from eclampsia.

PMID- 17000503
TI  - Maternal mortality: barriers to care at the health facility--health workers
      perspective.

PMID- 17000504
TI  - Misoprostol (alone) in second trimester terminations of pregnancy: as effective
      as Gemeprost?
AB  - Gemeprost (Cervagem) has been used widely compared with Misoprostol (Cytotec)
      alone in second trimester pregnancy termination. This prospective randomised
      trial was to evaluate the efficacy of intravaginal Misoprostol (alone) and
      Gemeprost in second trimester termination of pregnancy. A total of 54 women with
      27 on each arm were involved. A total of 25 patients (92.6%) in the Misoprostol
      group and 22 patients (81.5%) in the Gemeprost group delivered within 48 h. The
      Misoprostol group delivered earlier, although average number of tablets required
      were similar. The side-effects were not significant between the two groups in
      fact, but there was more pyrexia in the Gemeprost group (p = 0.004). Misoprostol
      in second trimester termination of pregnancy is clinically as effective and less
      costly than the standard regimen of Gemeprost.

PMID- 17000505
TI  - Secular trends in menarcheal age among Ghanaian women in Accra.
AB  - The Women's Health Study of Accra is a population-based cross-sectional survey
      that was conducted between March and September 2003 to assess the burden of
      disease in women in Accra. In addition to data relating to general health and
      living conditions, data on age at first menstruation was collected during the
      survey. A retrospective cohort analysis of the reported age at menarche was
      conducted using data from 2,644 women aged between 18 and 100 years. The median
      age of first menstruation of the entire cohort was 15.5 years and the median age
      of first menstruation among those aged <20 was 14.5 years. There was a
      statistically significant difference in median age at menstruation among the
      different age and socioeconomic groups. Multiple linear regression showed a
      significant decline of 0.2 years per decade in the mean age at menarche among
      Ghanaian women.

PMID- 17000506
TI  - Knowledge, attitude and practice of natural family planning methods in a
      population with poor utilisation of modern contraceptives.
AB  - Sub-Saharan Africa has one of the highest fertility rates in the world, which is
      further promoted by the low utilisation of modern contraceptive methods. Yet,
      many communities claim to have traditional methods of family planning that pre
      date the introduction of modern contraceptives, implying that contraception is a
      culturally acceptable norm. It was therefore postulated that the study population
      would have a high level of awareness and practice of natural methods of family
      planning. We aimed to obtain an insight into the extent and correctness of
      knowledge about natural family planning methods, and its practice as a guide to
      the general acceptance of contraception as a concept. Pre-tested structured
      questionnaires were administered to women of childbearing age in households
      properly numbered for primary healthcare activities. The level of awareness of
      natural family planning methods was significantly less than awareness for modern
      methods of contraception. The awareness rate for rhythm method, lactational
      amenorrhoea method and coitus interruptus was 50.7%, 42.1% and 36.1%,
      respectively. For all three national family planning methods, there is a steady
      decline between awareness, correct description of method and utilisation, a
      difference that was statistically significant in all cases. The sociodemographic
      factors of the responders had varying influence on utilisation of all three
      natural family planning methods studied. Rural dwellers practised the lactational
      amenorrhoea method significantly more often than urban dwellers. Significantly
      more Muslims than Christians with four children or more practised coitus
      interruptus or the rhythm method, while the use of lactational amenorrhoea method
      was significantly increased with the number of living children in both religious
      groups. There is a relatively low level of awareness of natural family planning
      methods in the study population, poor utilisation and wrong use of methods.
      Therefore, improving the correct level of information on natural family planning
      methods is likely to improve the use of both natural family planning and modern
      contraceptive methods.

PMID- 17000507
TI  - Cerebral malaria in pregnancy.

PMID- 17000508
TI  - A pregnant woman with genetic variants of butyrylcholinesterase and inflammatory
      bowel disease.

PMID- 17000509
TI  - Placenta praevia percreta with bladder invasion: an increasing obstetric
      catastrophe in modern practice.

PMID- 17000510
TI  - Primary psoas abscess following spontaneous vaginal delivery.

PMID- 17000511
TI  - Intrauterine infection of non-presenting twin: a rare occurrence.

PMID- 17000512
TI  - A case of stroke in pregnancy: the optimum management of such patients remains a
      challenge.

PMID- 17000513
TI  - Spontaneous cervical surgical emphysema and pneumomediastinum: a rare
      complication of childbirth.

PMID- 17000514
TI  - Luteoma of pregnancy.

PMID- 17000515
TI  - Spontaneous rupture of an ovarian teratoma discovered during an emergency
      Caesarean section.

PMID- 17000516
TI  - Ovarian cyst, cervical cyst or fundal fibroid.

PMID- 17000517
TI  - Ultrasound diagnosis of uterine dehiscence following mifepristone/misoprostol
      regime in early second trimester termination.

PMID- 17000518
TI  - Isolated one-sided cerebellar agenesis following an attempted medical termination
      of pregnancy.

PMID- 17000519
TI  - Successful microwave endometrial ablation (MEA) in uterus didelphys.

PMID- 17000520
TI  - Acute alopecia due to metformin treatment for polycystic ovarian syndrome.

PMID- 17000521
TI  - Boric acid for refractory Candida glabrata vaginitis.

PMID- 17000522
TI  - Respiratory distress caused by a unilateral hydrothorax as only manifestation of
      ovarian hyperstimulation syndrome.

PMID- 17000523
TI  - Ovarian pregnancy successfully treated with methotrexate.

PMID- 17000524
TI  - Management of menopausal symptoms associated with papillary carcinoma of thyroid.

PMID- 17000525
TI  - A benign solitary uterine leiomyoma on the pelvic peritoneum detected long after
      the hysterectomy for fibroids.

PMID- 17000527
TI  - Effect of hypothermia on blood-brain barrier permeability following traumatic
      brain injury in chronically ethanol-treated rats.
AB  - The objective of this study was to investigate the effect of hypothermia on the
      blood-brain barrier (BBB) disruption caused by traumatic brain injury (TBI) in
      chronically ethanol-treated rats. BBB permeability was measured using Evans blue
      (EB) dye. Arterial blood pressure levels of animals in hypothermic groups
      decreased significantly. The EB dye extravasation into the brain significantly
      increased in hypothermia and at 6 and 24 h after TBI. In ethanol-treated rats
      that were subjected to TBI, hypothermia led to a significant decrease in EB dye
      content in the brain at 24 h but not at 6 h after TBI when compared with TBI
      alone.

PMID- 17000528
TI  - Motor unit number estimation in cases with Carpal Tunnel Syndrome.
AB  - Degenerative or destructive processes result in the loss of whole motor neurons
      or in the peripheral axon portion. Loss of motor axons or neurons, and conduction
      blocks, are the basis of the weakness seen in most patients with neurogenic
      disease. The severity of the clinical deficit is directly associated with the
      number of the motor neurons or/and axons lost or blocked. So, it is important to
      find out the number of the functional motor units while evaluating neuromuscular
      disease. In neurological practice, motor unit number estimation studies are made
      in many diseases, especially in anterior horn disease. Entrapment neuropathies
      are one of these diseases. This study utilized motor unit number estimate testing
      in 50 patients with carpal tunnel syndrome and 34 controls without any systemic
      disease. The authors compared the results of these two groups and found
      statistical significance ( p < .0001).

PMID- 17000529
TI  - Neurocognitive differential diagnosis of dementing diseases: Alzheimer's
      Dementia, Vascular Dementia, Frontotemporal Dementia, and Major Depressive
      Disorder.
AB  - Similarities in presentation of Dementia of Alzheimer's Type, Vascular Dementia,
      Frontotemporal Dementia, and Major Depressive Disorder, pose differential
      diagnosis challenges. The current study identifies specific neuropsychological
      patterns of scores for Dementia of Alzheimer's Type, Vascular Dementia,
      Frontotemporal Dementia, and Major Depressive Disorder. Neuropsychological
      domains directly assessed in the study included: immediate memory, delayed
      memory, confrontational naming, verbal fluency, attention, concentration, and
      executive functioning. The results reveal specific neuropsychological comparative
      profiles for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal
      Dementia, and Major Depressive Disorder. The identification of these profiles
      will assist in the differential diagnosis of these disorders and aid in patient
      treatment.

PMID- 17000530
TI  - Acetylcholinesterase activity changes on visceral organs of VMH lesion-induced
      obese rats.
AB  - It is accepted that the tone of the parasympathetic nervous system increases
      after VMH lesion, whereas the sympathetic tone decreases. To reinforce
      investigations over outcomes from disturbances of the hypothalamic neuronal
      systems on peripheral autonomic nerve activity this study determined the
      acetylcholinesterase (AchE) activity in visceral organs, known as vagal targets,
      from VMH-lesioned obese rats. It was found that AchE activity was significantly
      increased in liver, pancreas, and stomach from these animals. However, it was not
      changed in kidneys, being decreased in spleen. The results suggest that AchE
      activity is enhanced in vagus innervated tissues to following up the unbalance of
      the autonomic nervous system as observed in VMH lesion-induced obesity.

PMID- 17000531
TI  - Triorthocresyl phosphate-induced neuronal losses in lumbar spinal cord of hens-
      an immunohistochemistry and ultrastructure study.
AB  - To investigate the neuronal losses of hens' spinal cords in the model of
      organophosphate-induced delayed neuropathy (OPIDN) and to analyze the impact of
      apoptosis on the pathogenesis of OPIDN. Adult hens were challenged with
      triorthocresyl phosphate (TOCP) at a single dose (750 mg/kg). Neuronal losses in
      the 3rd lumbar spinal cord (L3) were assessed by light-microscopy and electron
      microscopy methods at different days post exposure, respectively. The typical
      OPIDN signs were seen in the TOCP-exposed hens at about 9th day. The number of
      large nerve cells declined gradually. And these cells were verified as neurons by
      immunostained with neuronal marker NeuN. The expression of FasL reached proximal
      at about 9th day, decreased from 14th day. Neurons in TOCP exposed groups
      displayed degenerative morphologies in electronic microscopy. Some neurons showed
      apoptotic-like ultrastructure profiles at 5th day. The nuclear membrane was
      complete with chromatin condensed to the margins of nuclear membrane like a
      crescent-shaped body. Mitochondria morphologic changes appeared early (5 d)
      following exposure to TOCP, and developed in a time-dependent fashion. Apoptosis
      might be involved in the development of OPIDN, and play a role in the
      pathogenesis of OPIDN.

PMID- 17000532
TI  - Practical methods for the clinical assessment of information processing speed.
AB  - The rate at which individuals are capable of processing information is considered
      a sensitive indicator of brain dysfunction, particularly among clinical
      populations whose neurocognitive impairments generally are considered relatively
      mild in nature. Assessment of information processing speed often is confounded,
      however, by comorbid impairments in other constructs of neurocognition, including
      attentional capacity, visuospatial perception, language, immediate memory, and
      motor speed/coordination. This investigation examined the effect of controlling
      for various potential confounders on the strength of associations among several
      potential measures of information processing speed. Participants were 64 patients
      diagnosed with clinically definite multiple sclerosis. Analysis indicated
      consistent significant and positive associations among measures of processing
      speed, which generally persisted despite simultaneous statistical control of
      potential confounding factors. Results imply that examined confounding variables
      are similarly related to the measures of processing speed. Therefore, any of the
      measures of information processing speed considered in this study may be used as
      a proxy for the more direct measure of this construct derived from the Sternberg
      Memory Scanning Test.

PMID- 17000533
TI  - Calcium action on the membrane currents possessing the properties of mechano
      electric transducer currents in inner hair cells of the Guinea-pig cochlea.
AB  - In free-standing hair bundle, depolarization to +80 mV evoked a stable outward
      current and repolarization to -80 mV evoked a transient inward current
      attributable to the opening of mechano-electric transducer channels. The study
      investigated the Ca2+ dependence of this transducer-like membrane current in
      isolated inner hair cells of guinea-pig cochlea. The amplitude of outward
      currents increased and the rate of inward current decay, corresponding to
      adaptation kinetics, decreasing as the extracellular Ca2+ concentrations
      lessened, whereas the amplitude of outward current decreased and an adaptation
      accelerated as the extracellular Ca2+ elevated. Treatment with the cAMP agonist,
      8-bromo-cAMP, induced an effect similar to that caused by elevating the
      extracellular Ca2+.

PMID- 17000534
TI  - A preliminary study: validity and reliability of Turkish translation of migraine
      disability assessment (MIDAS) questionnaire in Turkish patients with chronic
      tension type headache.
AB  - We have tested Turkish version of the Migraine Disability Assessment (MIDAS)
      questionnaire in patients with tension type headache. Thirty-two patients who had
      a tension type headache were included. Turkish version of the MIDAS questionnaire
      was applied to all patients. Additionally, the patients were asked to keep a 90
      day diary. The day diary and the MIDAS questionnaire were compared at the end of
      the study period. We found that cronbach's alpha 0.82 and had good reliability.
      Our findings suggest that the MIDAS questionnaire that was originally designed
      for patients with migraine may be used in patients with chronic tension type
      headache.

PMID- 17000535
TI  - Visual function and execution of microsaccades related to reading skills, in
      cerebral palsied children.
AB  - This article investigates the ability of cerebral palsied (CP) children to
      execute microsaccades. One-hundred and five congenitally CP school aged children
      (6 to 15 years old), without severe mental retardation, were classified into
      three groups: those with spastic quadriplegi, spastic diplegics, and spastic
      hemiplegics on the basis of: (1) patient anamnesis, (2) IQ estimation, (3)
      evaluation of the microsaccadic skills with the Developmental Eye Movement test
      (DEM). Their performance in these tests was compared with a control group from
      the general pediatric population. IQ of the CP children ranged between 70 and
      100; the microsaccadic skills were severely affected: only 19% of the CP children
      had normal function, 20.9% of the CP children appeared with a pure oculomotor
      problem, 32.4% of the CP children had a visual-perceptual problem, and 27.7% of
      the CP children had a combined oculomotor and visual perceptual problem. CP
      children, in the absence of severe mental retardation, have disturbed visual
      skills and visual perception that usually leads to reading difficulties. It is
      also suggested that microsaccadic skills of CP children is an identifiable factor
      compounding the adverse effects of mental retardation on reading skills.

PMID- 17000537
TI  - Modeling brominated trihalomethane compounds in drinking water at a treatment
      plant in Beaumont, Texas.
AB  - The premise of this study is that the presence of bromide has a substantial
      effect on both the speciation and total formation of trihalomethane (THM).
      Consequently, models of water containing substantial bromide concentrations
      require refinement because they are only calibrated with raw water with high
      humic acid content. This study investigates and reports efforts on such
      refinement. The objectives of work reported in this paper are to formulate and
      validate a new correlative model that is based on physical principles and
      incorporates high levels of bromide that affect THM formation using raw water
      rich in both humic and fulvic acid. Two types of THM precursors are considered in
      the model discussed in this paper: (1) activated aromatic groups, which are more
      reactive with chlorine than with bromine, and (2) aliphatic groups, which are
      more reactive with bromine than with chlorine. Aliphatic and aromatic carbons are
      incorporated in the model by the inclusion of pertinent variables such as C/N and
      Br/Cl2 in the algorithm. The model also includes NH4+. This variable affects
      chlorine consumption that, in turn, potentially affects THM formation. For the
      first time ever, organic carbon to organic nitrogen and bromide to chlorine
      ratios is also used as variables potentially affecting THM formation when
      treating drinking water. The THM model formulated in this paper is an empirical
      model based on scientific principles and not simply a regression equation. The
      formulated model is pronounced valid based on a validation effort that employs a
      portion of an EPA database that was not used for model formulation.

PMID- 17000536
TI  - Spectral analysis of EEG in normal and sulfite oxidase deficient rats under
      sulfite administration.
AB  - This article investigated the possible neurotoxic effect of sulfite in normal and
      sulfite oxidase (SOX) deficients rats by evaluating EEG spectral analysis. Rats
      were divided into four groups: control (C), sulfite treated (25 mg/kg) (ST), SOX
      deficient (SD), and sulfite treated SOX deficient (STSD) groups. The qEEG
      spectral analyses of two spectral parameters including power and relative power
      were performed. The mean power of SD group was found to be increased compared to
      the all other groups and returned to control levels after sulfite administration.
      The power of the four frequency bands (delta, theta, alpha, beta) of the SD group
      corresponds to the mean power. EEG relative power increased in the delta band
      with concomitant decreases in power measured in the alpha frequency range. It was
      concluded that exogenous administration of sulfite affected the brain electrical
      activity in SOX deficiency, and improved neuroprotection.

PMID- 17000538
TI  - Modeling spatial variation of brominates trihalomethane in a water distribution
      system of Ontario, Canada.
AB  - Conventional approaches to characterize and model the formation of
      trihalomethanes (THM) species in the distribution system use either residence
      time or water temperature. A significant deviation of THM levels were observed at
      the beginning and the end of a selected distribution system in Ontario, which may
      be because the consumption rate of residual chlorine is not constant in the
      distribution system. The approach developed in this study incorporates water
      temperature and proceeds with a trend and decomposition modeling method to
      incorporate the traveled distance and to explain the seasonal THM variation in
      the distribution system. The model has been tested and verified using a database
      from the Bettravia distribution system in Ontario, Canada. The deviations at the
      extremes of the distribution system were minimized due to the modeling technique
      used to develop the model and by including more factors that affect THM formation
      in the distribution system. The agreement between predicted and measured THM
      values at the beginning and the end of the distribution system is pronounced. The
      model presented in this paper is a robust tool that may be used by SDWAA to
      evaluate regulatory options and justify potential regulations regarding THM
      levels of the drinking water distribution system.

PMID- 17000539
TI  - Summer exposure assessment of Cu and Zn in drinking water in Shanghai, China.
AB  - Daily exposures to chemicals in drinking water are of importance in risk
      assessment to human health. However, exposure assessment of chemicals in drinking
      water has seldom been performed in China. Until now, no such a detailed exposure
      assessment was reported in China. The aim of the present paper is to describe the
      scenes of daily exposure to Cu and Zn in drinking water by the population of
      Shanghai, China in the summer of 2003. A total of 163 volunteers and/or homes
      were selected to be statistically representative of the population of Shanghai,
      China. The Modified Consumption Habit Exposure Model (CHEM) method combined with
      the measurement of metals concentrations in stagnant water and actual ingested
      water was used to describe the daily exposure. The Consumption Habit Exposure
      Model method results showed that water consumption ranged from 1.7 to 2.2 L/day,
      varied with different age, gender and work location groups. Chemical results
      showed that the average Cu and Zn concentrations in stagnant water were much
      higher than those in actual ingested water (13.5 microg/L and 1.55 mg/L vs. 10.8
      microg/L and 0.29 mg/L). Exposure assessment results also showed that volunteers
      had the highest exposure from the time of after breakfast to before dinner, and
      had the lowest exposure during the 15 minutes before sleeping. It was also showed
      that there were few volunteers directly exposed to stagnant water, although six
      hours stagnant time can be reached in most of the homes in Shanghai in the
      morning. The mean daily exposures to Cu and Zn were 0.36 microg/kg/day and 0.01
      mg/kg/day. Daily intakes of Cu and Zn from drinking water by Shanghai people were
      1.8% and 4.4% of the World Health Organization recommendations for minimum total
      intakes of Cu and Zn for adults, respectively.

PMID- 17000540
TI  - Evaluation of pathogenic indicator bacteria in structural best management
      practices.
AB  - This study evaluated the bacteria removal efficiency, re-suspension and
      survivability within two structural Best Management Practices (BMPs) called
      Vortechs installed at two different sites in Providence, Rhode Island. Twelve
      rain storms were sampled during years 2004 and 2005. Five pathogenic indicator
      bacteria, E. coli, enterococci, fecal streptococci, total coliform, fecal
      coliform, were analyzed. Results showed that Vortechs was effective in partial
      removal of pathogenic indicator bacteria (PIB, 39-86%), however, the PIB
      concentrations after Vortechs treatment were still significantly high, which
      could limit the use of receiving waters and raise concerns for public health. The
      indicator bacteria concentrations in the sump water were 1.2-2.6 times higher
      than that contributed by the incoming stormwater. This result suggests some
      bacteria were re-suspended from the sediments within the Vortechs. Low bacterial
      survivability of bacteria was found in the sump water at both sampling sites;
      however, much lower bacteria concentrations were detected at Site 2, suggesting a
      higher bacteria contamination from highway runoff.

PMID- 17000541
TI  - Soybean-derived biofuels and home heating fuels.
AB  - It is environmentally enticing to consider replacing or blending petroleum
      derived heating fuels with biofuels for many reasons. Major considerations
      include the soaring worldwide price of petroleum products, especially home
      heating oil, the toxicity of the petroleum-derived fuels and the environmental
      damage that leaking petroleum tanks afford. For these reasons, it has been
      suggested that domestic renewable energy sources be considered as replacements,
      or at the least, as blending stocks for home heating fuels. If recycled soy
      restaurant cooking oils could be employed for this purpose, this would represent
      an environmental advantage. Renewable plant sources of energy tend to be less
      toxic than their petroleum counterparts. This is an important consideration when
      tank leakage occurs. Home fuel oil storage tanks practically always contain some
      bottom water. This water environment has a pH value that factors into heating
      fuel stability. Therefore, the question is: would the biofuel help or exacerbate
      fuel stability and furnace maintenance issues?

PMID- 17000542
TI  - Rhizosphere microbial activity during phytoremediation of diesel-contaminated
      soil.
AB  - To know microbial activity and diesel-removal efficiency influencing through
      plant roots, we examined the effect of the rhizosphere on phytoremediation of
      diesel-contaminated soils by alfalfa (Medicago sativa L.). Pots were treated with
      and without diesel and allowed to stabilize for 7 weeks, at which time four
      experimental/control groups were prepared: (1) planted diesel-contaminated soil,
      (2) unplanted diesel-contaminated soil, (3) planted uncontaminated soil, and (4)
      unplanted uncontaminated soil. Samples of rhizosphere and bulk soils were
      separately taken from all planted pots. After 7 weeks of alfalfa growth from
      seeds, the removal efficiencies in rhizosphere and bulk soil samples were 82.5%
      and 36.5 approximately 59.4%, respectively. The total microbial activity was
      highest in diesel-contaminated rhizosphere soils. Significantly more culturable
      soil bacteria and hydrocarbon-degraders were found in diesel-contaminated
      rhizosphere soil versus unplanted and uncontaminated bulk soil, with a greater
      increase seen in hydrocarbon-degraders (172-fold) versus general soil bacteria
      (14-fold). DGGE (Denaturing Gel Gradient Electrophoresis) analysis revealed that
      the bacterial community structure was most highly influenced by the combined
      presence of diesel contamination and plant roots (39.13% similarity compared to
      the control), but that diesel contamination alone had a higher influence (42.31%
      similarity compared to the control) than the rhizosphere (50.00% similarity
      compared to the control). Sequence analysis and BLAST searches revealed that all
      samples were dominated by members of alpha -, gamma -, delta - and epsilon 
      proteobacteria, and Chloroflexi. The rhizosphere samples additionally contained
      novel dominant members of alpha -proteobacteria and Cytophaga-Flexibacter
      Bacteroides, while the diesel samples contained additional dominant alpha 
      proteobacteria and the rhizosphere plus diesel samples contained other epsilon 
      proteobacteria. Collectively, these findings indicate that the presence of plant
      roots (i.e., a rhizosphere) had a greater effect on bacterial activity in diesel
      contamination than did the absence of diesel contamination, whereas diesel
      contamination had a greater effect on bacterial community structure. These novel
      findings provide new insight into the mechanisms of phytoremediation.

PMID- 17000543
TI  - Enhancing electrokinetic remediation of cadmium- contaminated soils with stepwise
      moving anode method.
AB  - This paper proposed an innovative approach by stepwise moving anode towards
      cathode to enhance the cadmium (Cd) removal from soil during the process of
      electrokinetic (EK) remediation. Fixed anode tests and moving anode tests were
      carried out for 60 hours to compare their performances. The anode-cathode spacing
      was 21 cm. Constant voltage grade of 1.0 V cm(-1) was applied in this study. The
      parameters included pH, electrical conductivity, current, Cd concentration and
      speciation distributions, energy consumptions, etc. It was found that the pH
      values in the moving anode tests were relatively lower than those of the fixed
      tests. In the moving anode test, the removal efficiency of Cd in the soils at the
      fraction of S4 was enhanced by 54.9% compared with that of the fixed anode tests.
      After 60 hours of treatment, approximately 80% of the spiked soils (100.63 mg x
      kg(-1) of Cd) in the system were successfully remedied in the moving anode tests;
      and the mean removal efficiency was 73% for actual field-contaminated soil (54.26
      mg x kg(-1) of Cd). It is effective to remedy actual contaminated soils. In
      addition, the cumulative energy consumptions were 59.29 kWhm(-3) and 31.52 kWhm(
      3) for the fixed and moving tests, respectively. The results revealed that the Cd
      removal efficiency was improved by the moving anode method. Moreover, less energy
      was consumed in the moving test. The proposed approach does not need to introduce
      extra chemicals nor adjust the pH in the system to enhance the Cd removal by EK
      remediation. The basic idea proposed in this paper provides a novel and
      environmental friendly method to enhance the EK remediation of heavy metals
      contaminated soils.

PMID- 17000544
TI  - Phosphorus removal characteristics in hydroxyapatite crystallization using
      converter slag.
AB  - This study was performed to investigate the phosphorus removal characteristics in
      hydroxyapatite (HAP) crystallization using converter slag as a seed crystal and
      the usefulness of a slag column reactor system. The effects of alkalinity, and
      the isomorphic-substitutable presence of ionic magnesium, fluoride, and iron on
      HAP crystallization seeded with converter slag, were examined using a batch
      reactor system. The phosphorus removal efficiencies of the batch reactor system
      were found to increase with increases in the iron and fluoride ion
      concentrations, and to decrease with increases in the alkalinity and magnesium
      ion concentration. A column reactor system for HAP crystallization using
      converter slag was found to achieve high, stable levels of phosphorus
      elimination: the average PO4-P removal efficiency over 414 days of operation was
      90.4%, in which the effluent phosphorus concentration was maintained at less than
      0.5 mg/L under the appropriate phosphorus crystallization conditions. The X-ray
      diffraction (XRD) patterns and Fourier transform infrared (FTIR) spectra of the
      crystalline material deposited on the seed particles exhibited peaks consistent
      with HAP. Scanning electron micrograph (SEM) images showed that finely
      distributed crystalline material was formed on the surfaces of the seed
      particles. Energy dispersive X-ray spectroscopy (EDS) mapping analysis revealed
      that the molar Ca/P composition ratio of the crystalline material was 1.72.

PMID- 17000545
TI  - Environmental contamination assessment of the surroundings of the ex
      ferrochromium smelter Dugi Rat, Croatia.
AB  - The objective of this study was to chemically characterize the soil samples
      affected by the dust emission and slag dumping from ferrochromium smelter, as
      well as uptake of metals by vegetation growing on that soil. There were 38
      samples collected altogether, including unpolluted background soil samples,
      polluted soil samples taken in the vicinity of the factory, slag material, bottom
      and fly ash. Grass material was also taken from both polluted and unpolluted
      soil. All samples were analyzed with energy dispersive X-ray fluorescence
      (EDXRF). The results showed (especially for chromium and manganese) metal
      concentrations in soil samples taken in the vicinity of the factory increased up
      to 56 times in relation to normal background soil concentrations. Slag material,
      fly and bottom ash were highly enriched with chromium, manganese and nickel.
      There was a significant chromium uptake by vegetation growing on the contaminated
      soil.

PMID- 17000546
TI  - Dynamic response of denitrifying poly-P accumulating organisms batch culture to
      increased nitrite concentration as electron acceptor.
AB  - Despite the fact that, in practice, enhanced biological phosphorus removal (EBPR)
      is often combined with biological nitrogen removal (BNR), the feasibility of
      nitrite (an intermediate in BNR) utilization, by denitrifying poly-P accumulating
      organisms (DPAO) is still unclear. In this study, the effect of nitrite on the
      EBPR was evaluated by investigating the dynamic response of DPAO to the gradual
      change of electron acceptor from nitrate to nitrite in an anaerobic/anoxic
      sequencing batch reactor (SBR). Under the nitrate condition, excellent EBPR was
      achieved, characterized by the DPAO biomass dominating in the sludge (51%-72% of
      VSS). Of the DPAO, 34% was the DPAOnitrate that could only use nitrate as
      electron acceptor, and 66% was the DPAOnitrite that could use nitrate/nitrite as
      electron acceptor. Nitrite in excess of 12 mg N/L had inhibition effect on the
      anoxic phosphorus uptake. As the electron acceptor changed, EBPR degraded slowly
      due to the gradual exclusion of the DPAOnitrate out of the reactor. The
      DPAOnitrite, therefore, became the single type of DPAO under the nitrite
      condition, and finally occupied only 33%-49% of the total sludge of VSS.
      Simultaneously, glycogen accumulating organisms (GAO), the competitor to the DPAO
      for substrate in the anaerobic phase, was significantly enhanced and grew to
      dominance in the reactor (46-62% of VSS). Also, the periodical exposure of sludge
      to the increased nitrite concentration elevated the inhibition level of nitrite
      for the anoxic phosphorus uptake (80 mg N/L). More attention should be paid to
      nitrite accumulation at full-scale wastewater treatment plants from the
      perspective of the stability of EBPR performance.

PMID- 17000547
TI  - Toxicants accumulation rates and effects in Mytilus trossulus and Nereis
      diversicolor exposed separately or together to cadmium and PAHs.
AB  - Two invertebrates, Mytilus trossulus and Nereis diversicolor, were exposed in
      aquaria to cadmium (50 microg L(-1)) and a mixture of three- to six-ring PAHs (2
      microg L(-1) each) for 2 weeks. Organisms of two species were reared in separate
      tanks or together in the same one. Concentrations of Cd, PAHs and activities of
      selected biomarkers: catalase (CAT), glutathione S-transferase (GST) and
      acetylcholinesterase (AChE) were measured within 2 weeks of exposure. When reared
      separately, higher accumulation rates for cadmium were measured in mussels (16.4
      microg day(-1) g(-1) d.w. lipid-free tissue) than in polychaeta (0.7 microg Cd g(
      1) d.w day(-1)). When co-exposed, a difference in bioaccumulation was maintained
      but the accumulation rate in N. diversicolor increased to 1.0 microg Cd g(-1)
      d.w. day(-1) and decreased to 9.6 microg Cd g(-1) d.w. day(-1) in M. trossulus.
      On the contrary, faster bioaccumulation rates of PAHs were seen in polychaeta
      than in mussels when exposed separately (19.3 vs 4.5 microg PAHs day(-1) g(-1)
      lipid weight) than together (12.0 vs 3.1 microg PAHs g(-1) l.w. day(-1)).
      Substantial changes in the bioaccumulation patterns of the different M. trossulus
      organs were observed when both species were reared together. Biochemical
      responses indicated no effect of the accumulated contaminants on AChE,
      enhancement of CAT in both species and depletion of GST in Mytilus. The observed
      differences are discussed in terms of different bioavailability of contaminants,
      route of uptake and detoxification mechanism, under the two modes of exposure.

PMID- 17000548
TI  - Biosorption potential of the macrofungus Ganoderma carnosum for removal of
      lead(II) ions from aqueous solutions.
AB  - This paper reports the utilization of a macro-fungus Ganoderma carnosum as a
      biosorbent material for the removal of lead(II) ions from aqueous solutions. The
      biosorption potential of G. carnosum was investigated by batch experiments. The
      influences of physico-chemical parameters like pH, biosorbent dosage, contact
      time and initial metal ion concentration were evaluated. The biosorption
      equilibrium was attained in 10 minutes. Equilibrium biosorption data were
      analyzed by the Freundlich, Langmuir and Dubinin-Radushkevich (D-R) isotherm
      models. Maximum biosorption capacity of biosorbent was found to be 22.79 mg g(-1)
      (1.10 x 10(-4) mol g(-1)) at the pH value of 5.0. The biosorbent was regenerated
      using 10 mM HCl solution, with up to 96% recovery, and reused four times in
      biosorption-desorption cycles successively. Biosorption efficiency of G. carnosum
      was also examined in a real effluent. The mechanism of the biosorption was
      investigated with FTIR, SEM and EDAX analysis and the findings suggested that the
      biosorption process involved in ion exchange as dominant mechanism as well as
      complexation. The ion exchange mechanism was also confirmed by the mean free
      energy value obtained from D-R isotherm model.

PMID- 17000549
TI  - Accumulation of some metals in muscles of five fish species from lower Nitra
      river.
AB  - This paper reports the results of accumulated selected metals concentrations (Fe,
      Mn, Zn, Cu, Ni, Co, Cr, Pb, Cd, Hg and meHg) in the muscle of five common Slovak
      fish species (Chub-Leuciscus cephalus, Common carp-Cyprinus carpio, Prussian carp
      Carassius gibelio, Roach-Rutilus rutilus, and Wels catfish-Silurus glanis).
      Furthermore, correlations among the selected metals and order of metal
      accumulation in the fish muscle were determined. The concentrations of metals
      (mg/kg wet weight basis) ranged as follows: Fe 3.70-21.10; Mn 0.27-1.50; Zn 3.72
      42.82; Cu 0.26-1.82; Ni 0.02-0.29; Co 0.06-0.28; Cr 0.09-0.28; Pb 0.08-34.59; Cd
      0.06-2.76, Hg 0.34-3.64 and meHg 0.08-1.20. The level of lead and mercury
      exceeded the maximum allowed concentration in Slovakia by the Codex Alimentarius
      for safe human consumption (0.2 and 0.5 mg/kg, respectively) in the majority of
      samples (94.6 and 82.1%, respectively). Content of Cd (0.88 +/- 0.76 mg/kg wet
      weight) in the fish muscle exceeded maximum allowed levels (0.05 mg/kg) in all
      samples. An average, the order of metal concentrations in the fish muscle was: Fe
      > Zn > Pb > Cd > Hg > Cu > Mn > meHg > Ni > Cr > Co.

PMID- 17000550
TI  - A hydrogen peroxide/ microwave advanced oxidation process for sewage sludge
      treatment.
AB  - This study focused on the efficacy of the microwave/hydrogen peroxide advanced
      oxidation process (MW/H2O2-AOP) on the secondary sludge treatment. The results
      indicated that at temperatures of 80 degrees C and above, essentially all of the
      chemical oxygen demand (COD) was solubilized by the combined MW/H2O2-AOP. This
      process also solubilized nutrients (nitrogen, phosphorus and metals) from sludge
      which can be extracted for other purposes, such as struvite crystallization.
      Based on a stoichiometric molar ratio of 1:1:1 for Mg:NH3:PO4, ammonia was found
      to be the limiting nutrient without any H2O2 addition in the process at all
      temperatures. With the addition of H2O2, ortho-phosphate became the limiting
      nutrient. In all treatments, magnesium was non-limiting, thus magnesium addition
      is not required for subsequent struvite crystallization. The MW/H2O2-AOP also
      enhanced the pasteurization or sterilization of sludge. The MW/H2O2-AOP provides
      novel sludge management options for the wastewater industry, not only in
      solubilization of carbon for further methane production, but also in nutrients
      extraction for crystallization for use as fertilizer.

PMID- 17000551
TI  - Historical assessments and comparisons of benthic communities and physical
      habitat in two agricultural streams in California's San Joaquin watershed.
AB  - This study was designed to assess trends in physical habitat and benthic
      communities (macroinvertebrates) annually in two agricultural streams (Del Puerto
      Creek and Salt Slough) in California's San Joaquin Valley from 2001 to 2005,
      determine the relationship between benthic communities and both water quality and
      physical habitat from both streams over the 5-year period, and compare benthic
      communities and physical habitat in both streams from 2001 to 2005. Physical
      habitat, measured with 10 metrics and a total score, was reported to be fairly
      stable over 5 years in Del Puerto Creek but somewhat variable in Salt Slough.
      Benthic communities, measured with 18 metrics, were reported to be marginally
      variable over time in Del Puerto Creek but fairly stable in Salt Slough. Rank
      correlation analysis for both water bodies combined showed that channel
      alteration, embeddedness, riparian buffer, and velocity/depth/diversity were the
      most important physical habitat metrics influencing the various benthic metrics.
      Correlations of water quality parameters and benthic community metrics for both
      water bodies combined showed that turbidity, dissolved oxygen, and conductivity
      were the most important water quality parameters influencing the different
      benthic metrics. A comparison of physical habitat metrics (including total score)
      for both water bodies over the 5-year period showed that habitat metrics were
      more positive in Del Puerto Creek when compared to Salt Slough. A comparison of
      benthic metrics in both water bodies showed that approximately one-third of the
      metrics were significantly different between the two water bodies. Generally, the
      more positive benthic metric scores were reported in Del Puerto Creek, which
      suggests that the communities in this creek are more robust than Salt Slough.

PMID- 17000552
TI  - Man-caused uranium contamination of biosphere objects in the territory of
      Kyrgyzstan.
AB  - The paper presents data on uranium content in water, soils and plants in the
      territories of the largest uranium geochemical provinces of Kyrgyzstan where
      uranium mining and production complexes functioned and operated until the 1960s.
      The migration of uranium and its contamination of the biosphere are discussed.
      The paper provides recommendations on using natural phytomeliorants that would
      discriminate uranium, fix the ground, reduce the risk of mudflows formation and
      the degree of uranium contamination of the territory, and also facilitate the
      recovery of the disturbed natural mountainous ecosystems.

PMID- 17000553
TI  - Standardization of p-creatinine assays and use of lean body mass allow improved
      prediction of calculated glomerular filtration rate in adults: a new equation.
AB  - OBJECTIVE: To evaluate the Cockcroft-Gault (CG) equation, using various body
      weight expressions, and the Sawyer equation in predicting glomerular filtration
      rate (GFR) using an enzymatic and zero-calibrated Jaffe plasma-creatinine assay,
      and to derive a new robust equation in adults. MATERIAL AND METHODS: The CG
      weight measures included total, ideal and adjusted body weight (ABW; lowest of
      total and ideal) and two lean body mass (LBM) expressions, while the Sawyer
      equation is based primarily on LBM. Iohexol clearance was used to measure GFR.
      One derivation set (n = 436; enzymatic assay) was used to evaluate and bias
      adjust existing equations when indicated, and to derive a new equation based on
      plasma-creatinine, age, gender and the body weight measure yielding the best
      adjusted R2. All equations were then validated in a separate set (n = 414; Jaffe
      assay). RESULTS: The existing equations all performed similarly in both sets.
      Prediction errors of equations based on LBM showed no correlation with BMI. The
      CGABW and Sawyer equations performed best. The new equation with LBM yielded the
      highest adjusted R2. In the combined set (n = 850), its accuracy (86 %/98 % of
      estimates within 30 %/50 % of measured GFR) was significantly better than for the
      CGABW (79 %/95 %) and Sawyer equations (79 %/93 %) (p<0.001) for each 30 mL/min
      GFR subgroup within +/-30 % and +/-50 %, except within +/-30 % >120 mL/min.
      Prediction error did not correlate with BMI, age or gender. CONCLUSION: A new
      creatinine-based equation derived in a mainly Caucasian patient sample is a
      better predictor of GFR than CG-type equations irrespective of the body weight
      measure used or, if bias-adjusted, when using zero-calibrated creatinine assays.

PMID- 17000554
TI  - Relationship between PTEN gene expression and differentiation of human glioma.
AB  - OBJECTIVE: To investigate the relationship between PTEN gene expression and
      differentiation of glioma. MATERIAL AND METHODS: The quantitative real-time
      reverse transcription-polymerase chain reaction (RT-PCR) method was applied to
      detect PTEN mRNA levels in glioma tissues. Tumor-adjacent normal tissues and
      benign brain tumors were used as controls. Relative PTEN mRNA levels were
      determined as the ratio of PTEN and GAPDH, which were correlated with the
      clinical-pathological results. RESULTS: PTEN mRNA levels were significantly lower
      in the glioma tissues than in the benign brain tumors and tumor-adjacent normal
      tissues, whereas there were no statistical differences between benign brain tumor
      and the tumor-adjacent normal tissues. According to the pathological
      examinations, PTEN mRNA levels were higher in the high differential glioma than
      the low differential glioma. CONCLUSIONS: PTEN gene expression was suppressed in
      the glioma, which is related to the clinical-pathological results. It is
      suggested that determination of PTEN mRNA levels by RT-PCR could be a novel
      marker of disease classification.

PMID- 17000555
TI  - High-dose, short-term, anti-inflammatory treatment with dexamethasone reduces
      growth and augments the effects of 5-fluorouracil on dimethyl-alpha
      benzanthracene-induced mammary tumors in rats.
AB  - OBJECTIVE: To evaluate the effects of dexamethasone (DXM) alone or in combination
      with 5-fluorouracil (5-FU) on dimethyl-alpha-benzanthracene (DMBA)-induced
      mammary tumors in rats. MATERIAL AND METHODS: Female Sprague-Dawley rats were
      divided into 4 groups receiving: 1) saline (controls), 2) DXM (3 mg/kg), 3) 5-FU
      (1.5 mg/kg) and 4) DXM and 5-FU combined. The drugs were given i.p. every day for
      4 days. Interstitial fluid pressure (Pif) and tumor growth were determined in all
      tumors on days 1, 5 and 7 using the "wick-in-the needle" technique and by
      external size measurements, respectively. Vessel density and inflammatory cell
      infiltration of tumor tissue were analyzed by immunohistochemistry. RESULTS: DXM
      treatment significantly retarded tumor growth and reduced Pif. Treatment with a
      combination of DXM and 5-FU reduced tumor size significantly more than any of the
      agents alone (p<0.01-0.001). Enhanced uptake of 5-FU by DXM treatment was
      demonstrated by microdialysis. There were no differences in the density of CD31
      positive vessels after DXM or 5-FU treatment, but inflammatory cell infiltration
      of tumor tissue was significantly reduced after DXM treatment. CONCLUSIONS: Our
      data suggest that DXM may be beneficial as an adjuvant to chemotherapy in the
      treatment of mammary cancer by increasing the uptake of 5-FU in the tumor.

PMID- 17000556
TI  - Pleural injury and pleurisy-induced progelatinase B/proMMP-9 is associated with
      markers of neutrophil degranulation.
AB  - OBJECTIVE: Progelatinase B/proMMP-9 has recently been identified as an indicator
      of pleural inflammation, presumably originating from granulocytes. The aim of
      this study was to verify the origin of progelatinase B by simultaneous estimation
      of specific markers of neutrophil recruitment and activation in pleural effusions
      following induced pleurisy and pleural injury. MATERIAL AND METHODS: Sixty-three
      samples of pleural fluid from patients undergoing therapeutic talc pleurodesis (n
      = 8) and explorative thoracoscopy (n = 3) collected before and at different time
      intervals after the intervention were analyzed for progelatinase B and neutrophil
      gelatinase-associated lipocalin (NGAL)-gelatinase complex by substrate
      electrophoresis, for myeloperoxidase (MPO) and interleukin-8 (IL-8) by
      immunoadsorbent sandwich assay, as well as for leukocyte count, C-reactive
      protein (CRP) and total protein (TP). RESULTS: A significant increase in free and
      NGAL-complexed progelatinase B, MPO and IL-8 was recorded within 48 h following
      treatment in all subjects. Progelatinase B was strongly correlated with NGAL
      gelatinase complex (r = 0.88, p = 0.001), MPO (r = 0.81, p = 0.001), neutrophil
      count (r = 0.75, p = 0.01) and IL-8 (r = 0.71, p = 0.001), but not with CRP and
      TP. CONCLUSIONS: The results support the neutrophil origin of the proenzyme,
      which confirms progelatinase B as an indicator of a local inflammatory reaction.
      Quantifying the inflammatory reaction may be helpful in the evaluation of both
      the technical variants of therapeutic pleurodesis and finer discrimination of
      paraneoplastic effusions.

PMID- 17000557
TI  - Effects of oxidized low- and high-density lipoproteins on gene expression of
      human macrophages.
AB  - OBJECTIVE: Oxidized low-density lipoprotein (ox-LDL) is a major factor in foam
      cell formation, whereas the role of oxidized high-density lipoprotein (ox-HDL) in
      this process is not known. The objective of the present study was to examine the
      effects of ox-LDL and ox-HDL on the gene expression of cultured human
      macrophages. MATERIAL AND METHODS: Gene expression of human macrophages was
      studied after incubation for 1 day and 3 days with native and oxidized LDL and
      HDL using cDNA expression array. Expression of granulocyte-macrophage colony
      stimulating factor 1, which was constantly up-regulated by ox-LDL and down
      regulated by ox-HDL after 1- and 3 days of incubation in cDNA microarray
      experiments, was verified by quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR). RESULTS: Genes that showed altered expression were divided
      into six groups; 1) lipid metabolism, 2) inflammation, growth and hemostasis, 3)
      matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases, 4)
      enzymes, 5) structural and binding proteins and 6) annexins. CONCLUSIONS: The
      microarray method was found to be applicable in analyzing changes in gene
      expression induced by oxidized lipoproteins in cultured human macrophages. Our
      results reflect different functional roles of ox-LDL and ox-HDL in foam cell
      formation.

PMID- 17000558
TI  - External dose rates in radioiodine treatment of benign goitre: estimation versus
      direct measurement.
AB  - OBJECTIVE: According to European recommendations, the external dose rate (ED) in
      radioiodine-treated goitre patients can be determined by estimating from
      calculation of the residual activity (RA) in the patient based on radioiodine
      uptake measurements or by measuring ED directly. In the European guidelines,
      "Radiation Protection 97", it is assumed that an RA of 600 MBq (131)I causes an
      ED of 30 microSv/h at a distance of 1 m. This implies a slope of 0.05
      microSv/h/MBq for the ratio ED/RA relationship, but, theoretically, this ratio is
      higher, at 0.07, a difference that is due to measurement in air versus in a
      scattering medium. We sought to investigate what the true ratio might be.
      MATERIAL AND METHODS: Sixty-six patients scheduled for radioiodine treatment of
      benign goitre (mean size 102 mL, range 20-440), who received (131)I orally (mean
      984 MBq, range 173-3700) were examined. After 24 h and 96 h iodine uptake
      percentage we examined 7269 patients scheduled for radioiodine treatment of
      benign goitre (mean size 1042 mL, range 20-440) who received (131)I orally (mean
      101,100 MBq, range 180-3700). After 24 h and 96 h, the iodine uptake was
      determined, RA calculated and ED measured using a hand-held dosimeter. RESULTS:
      At 24 and 96 h, we observed a slope ratio of 0.103 microSv/h/MBq (95 % CI:
      0.09564-0.111) and 0.101 microSv/h/MBq (95 % CI: 0.0915-0.11107), respectively,
      for the ED/RA relationship. None of the confidence intervals included the value
      0.05 microSv/h/MBq, reflecting that the observed slopes differed significantly
      from the expected slope (p < 0.001). Consequently, an RA of 600 MBq typically
      causes an ED of 60 and not 30 microSv/h, and therefore dose rates based on
      radioiodine uptake measurements and established assumptions were only about half
      as high as the directly measured values. We noticed that with an RA roughly below
      450 MBq, the anticipated slope of 0.05 microSv/h/MBq is within the prediction
      interval of our claimed ratio, therefore we cannot rebut the anticipated slope
      for lower doses. CONCLUSIONS: Dose-rate estimates based on radioiodine uptake
      measurements and established assumptions were only about half as high as the
      directly measured values in patients receiving doses higher than the widely
      accepted limits for outpatient treatment. This finding may have substantial
      implications for us, in that it makes a considerable difference whether the
      radiation precautions are taken to limit doses to the patient's surroundings and
      for deciding if a patient may or may not be regarded as an outpatient, as well as
      for the safe discharge of an inpatient from hospital.

PMID- 17000559
TI  - Evidence for systemic oxidative stress in tobacco chewers.
AB  - OBJECTIVE: To evaluate erythrocyte malondialdehyde (MDA) levels and activities of
      superoxide dismutase (SOD) and glutathione reductase (GR) in tobacco chewers, in
      view of possible oxidative stress in oral smokeless tobacco. MATERIAL AND
      METHODS: Sixty healthy male tobacco chewers, aged 30.6+/-4.7 years with a 3 to 10
      year (7.37+/-2.1) history of tobacco chewing, were included in the study. Thirty
      two healthy male volunteers, aged 26.5+/-4.8 years, served as controls. All the
      participants were from the same community and of similar dietary habits. RESULTS:
      The erythrocyte MDA level and activities of erythrocyte SOD and GR were
      estimated. There was a significant duration- (tobacco chewing) dependent increase
      in erythrocyte MDA levels along with a significant duration- (tobacco chewing)
      dependent decrease in erythrocyte SOD and GR activity. CONCLUSION: Oral smokeless
      tobacco causes a duration-dependent increase in oxidative stress.

PMID- 17000560
TI  - Interaction between Chlamydia pneumoniae seropositivity, inflammation and risk
      factors for atherosclerosis in patients with severe coronary stenosis.
AB  - OBJECTIVE: To investigate whether Chlamydia pneumoniae (Cpn) seropositivity in
      patients with suspected coronary artery disease (CAD) (n = 81) is associated with
      increases in markers of inflammation, the severity of coronary atherosclerosis,
      and traditional risk factors for cardiovascular events. MATERIAL AND METHODS: The
      severity of coronary atherosclerosis was ranked by Gensini score. Inflammation
      and endothelial dysfunction were evaluated using white blood cell counts and
      levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, tumour necrosis
      factor-alpha (TNF-alpha), interleukins 1beta and 6 (IL-1beta, IL-6), soluble
      intercellular adhesion molecule-1 (sICAM-1), E-selectin and oxidized LDL (oxLDL),
      and these were compared between Cpn-seropositive and seronegative individuals.
      RESULTS: IgA and IgG Cpn seropositivity were significantly associated with the
      presence of CAD (p = 0.005) and were independent predictive factors for the
      severity of coronary atherosclerosis (p = 0.005). Elevated levels of IL-6 (p =
      0.027) and triglyceride (p = 0.038) and low levels of high-density lipoprotein
      cholesterol (HDL-C) (p = 0.038) were significantly predicted by Cpn IgA and IgG
      seropositivity. CONCLUSIONS: Seropositivity for Cpn is a risk factor for patients
      with significant angiographically documented coronary stenosis. Additionally, Cpn
      seropositivity was significantly associated with dyslipidemia and elevated IL-6,
      known risk factors for CAD. These observations indicate that Cpn infection may be
      one entry point to the causal or contributory pathways that lead to
      atherosclerosis and its clinical manifestations.

PMID- 17000561
TI  - Systemic and local cytokine patterns during total hip surgery.
AB  - OBJECTIVE: Increased levels of inflammatory cytokines have been described in
      musculoskeletal injury. Total hip replacement is major musculoskeletal surgery,
      and in the present study this operation was used to investigate systemic and
      local cytokine patterns during musculoskeletal trauma. MATERIAL AND METHODS:
      Blood was sampled before, during and after surgery in 10 patients given total hip
      replacement. Samples of arterial blood and local blood from the femoral canal
      were analysed for proinflammatory and anti-inflammatory cytokines. RESULTS:
      Surgery induced significant increases in arterial and local levels of interleukin
      6 (IL-6) (p = 0.000, respectively) with the highest levels at 4 h after
      operation. There were significantly higher local levels of IL-6 than arterial
      levels. Interleukin 1beta (IL-1beta) was not significantly influenced by surgery
      at any time (p = 0.800 and 0.300 for local and arterial levels, respectively),
      nor was tumour necrosis factor alpha (TNFalpha) (p = 0.375 and 0.547 for local
      and arterial levels, respectively). Local levels were higher than arterial levels
      for IL-1beta and for TNFalpha. At the end of the operation, local levels of
      interleukin 10 (IL-10) were significantly reduced (p = 0.036), while surgery did
      not influence the arterial levels of IL-10 (p = 0.235). There were no significant
      differences in local and arterial levels of IL-10 (p = 0.558). CONCLUSIONS: The
      study indicates that a major musculoskeletal operation on otherwise healthy
      patients is associated with fairly modest reactions of inflammation, both
      systemically and locally.

PMID- 17000563
TI  - Policy Interpretation Network on Children's Health and Environment.
AB  - AIM: The main objective of PINCHE is to provide policy recommendations aiming at
      protecting children's health and environment based on completed scientific
      research. The project focused on four themes: indoor and outdoor air pollutants,
      carcinogens, neurotoxicants, and noise. The data were evaluated in workpackages
      on exposure assessment, epidemiology, toxicology, and risk and health impact
      assessment. The data were analysed according to a framework of questions. The
      workpackage on socioeconomic factors studied the influence of socioeconomic
      status on exposures and on health effects. In the workpackage on science-policy
      interface, recommendations on how to improve children's environmental health were
      formulated. RESULTS: The policy recommendations resulting from the analysis were
      grouped according to relevant policy levels: European Commission or the European
      Parliament, member states and other stakeholders at regional or local level.
      These recommendations are general guidelines for taking action. Regional
      differences and variation must be reflected when policy is actually implemented.
      In addition, recommendations related to education and personal behaviour are
      presented in the reports. CONCLUSIONS: The policy recommendations are important
      input for policy advisers, policy makers and public health authorities at all
      policy levels. The recommendations are also of direct relevance to interest
      groups, such as environmental NGOs including child health and advocacy groups.
      The policy recommendations for each policy level were prioritized. High
      priorities were given to reduce exposure to environmental tobacco smoke,
      transport related air pollution, indoor air and mercury.

PMID- 17000564
TI  - Paediatric environmental health history taking: why bother?
AB  - Environmental health history taking is often not part of standard medical history
      taking for clinical physicians. During recent years attention has been placed on
      home environments and asthma and allergies, high caloric intake and obesity and
      type 2 diabetes mellitus, yet environmental health history taking still remains
      relatively uncharted terrain for the clinical physicians of today. While the
      reasons for this are certainly varied, ignorance of environmental influences,
      ignorance of environmental pollutants, politics and prejudices will certainly
      play a role. We suggest a simple manner of environmental health history taking,
      and discuss the importance of the subject in our modern-day clinical practice.

PMID- 17000566
TI  - Children's environmental health: why should social disparities be considered?
AB  - BACKGROUND/METHODS: The aim of workpackage 5 'Environmental exposures and
      children's health: impact of socioeconomic factors' in the EU-funded network
      PINCHE (Policy Interpretation Network on Children's Health and Environment) was
      to review and interpret the current knowledge of social inequalities in
      environmental exposures and children's health. Socioeconomic factors may impact
      on children's environmental health in two ways: 1) environmental exposures may
      differ according to socioeconomic status; 2) given a certain level of harmful
      environmental exposure, socioeconomic factors may modify the health effects by
      influencing the susceptibility characteristics of children. RESULTS: There is a
      lack of information to evaluate and quantify the effect of socioeconomic factors
      on environmental exposures and children's health in Europe. In most circumstances
      there seems to be an inverse social gradient with increased burden concerning
      exposures and health outcomes in children of lower social status. CONCLUSIONS:
      There is a need to improve research on social inequalities in children's health
      and environment. Because of the complexity, integrated approaches and a
      combination of different intervention measures and policies are necessary to
      reduce environmental exposure and adverse health effects in children.
      Paediatricians may contribute to improvement of children's environmental health
      by risk communication and health advocacy at community and governmental level.

PMID- 17000565
TI  - Today's epidemics in children: possible relations to environmental pollution and
      suggested preventive measures.
AB  - BACKGROUND: Facts and hypotheses on the relationship between some children's
      diseases or disorders and external stressors during the developmental stage of a
      child, both prenatally and postnatally are described in literature. In this paper
      the following changes in patterns and causes of the main childhood illnesses are
      summarized and recommendations for actions are made. Prematurity. Intra-uterine
      growth restriction. Testicular dysgenesis syndrome. Type I and Type II diabetes.
      Asthma, atopy and hay fever. Autism. Attention deficit hyperactivity disorder
      (ADHD). Learning disabilities. Cancer. Obesity. Hearing problems. RESULTS:
      Literature provides a growing amount of information on changing patterns in
      childhood diseases. CONCLUSIONS: The following recommendations for action are
      formulated: Immediate research on endocrine disrupters in relation to
      prematurity. Diabetes: avoid Maillard Compounds in liquid baby food and in food
      in general: promote breastfeeding. Asthma: avoid exposure to smoking, the use of
      chemical household products, dioxin and dioxin-like chemicals, and avoid air
      pollution with high levels of particulate matter, especially around conception,
      during pregnancy and in the first years of life. Autism: more research on
      incidence and causes. ADHD and learning disabilities: more research on prevalence
      and causes. Preventions: 1) preconception counselling to avoid potentially
      harmful substances; 2) controlling and further lowering levels of polychlorinated
      biphenyls, lead and methyl mercury. Cancer: promote breastfeeding, carry out
      research into effects of foetal exposure to internal fission-product
      radionuclides. Obesity: stop smoking in pregnancy, avoid parental obesity, longer
      night sleep. Hearing problems: lower noise levels in discotheques, promote the
      day-evening-night level to avoid noise (longer night sleep).

PMID- 17000567
TI  - PINCHE's policy recommendations on noise: how to prevent noise from adversely
      affecting children.
AB  - BACKGROUND: Noise can have auditory and non-auditory effects on children. Very
      few noise episodes affect children's hearing instantaneously; most effects are
      long-term and cumulative. Describing the risks of noise on children's health and
      well-being in a life-course perspective can illustrate the prospects of
      cumulative effects. CONCLUSION: The policy recommendations the Policy
      Interpretation Network on Children's Health and Environment (PINCHE) prepared for
      each age group or setting are described here.

PMID- 17000568
TI  - Children's health and mercury exposure.
AB  - The reason why mercury is dangerous is that once released into the environment it
      cannot be removed and is rapidly transformed by microorganisms into organic
      compounds that tend to bioaccumulate and biomagnify in animals. The principal
      organic compound is methylmercury (MeHg). The primary route of exposure to MeHg
      for humans is consumption of fish. The safe dose (reference dose, RfD) of MeHg
      that can be consumed without neurotoxicological consequences is 0.1 microg per kg
      b.w./day. According to available data, the whole population of certain European
      countries or people who consume large quantities of fish are exposed to doses of
      MeHg that exceed the RfD. Given this level of mercury exposure, in order to avoid
      or reduce the expected neurotoxic consequences on foetuses we propose the
      following strategy: 1) At present the most reasonable solution for pregnant women
      (and small children) is to reduce substantially or completely avoid fish intake.
      2) In the medium term the European Community should evaluate the technical and
      economic feasibility of breeding uncontaminated fish in order to reduce the
      drawbacks of banning fish consumption. 3) In the long term there is no
      alternative to substantially reducing mercury emissions worldwide.

PMID- 17000569
TI  - Lead neurotoxicity in children: is prenatal exposure more important than
      postnatal exposure?
AB  - Numerous studies indicate that low-level lead poisoning causes mild mental
      retardation and low IQ scores in children. The general mean lead intake in the
      adult European population corresponds to a reassuring 14% (0.5-56%) of the
      tolerable daily intake: at this low level of exposure only few children (less
      than 10%) have blood lead levels (PbB) higher than 10 microg/dl, previously
      considered the PbB of concern. In more recent years data now suggest that even
      when 'the lifetime average blood lead concentration' is below 10 microg/dl an
      inverse association exists with intelligence quotient (IQ) scores. Two-thirds (45
      75%) of lead in blood, however, comes from long-term tissue stores and this is
      especially true for newborn infants and pregnant women. Several data suggest that
      for lead the main toxic event is prenatal exposure: therefore we should focus our
      attention on maternal lead stores and whenever possible avoid their mobilization
      during pregnancy. In this regard we should design appropriate studies to confirm
      whether dietary supplementations can reduce bone resorption and lead mobilization
      during pregnancy. The hypothesis that the amount of maternal bone lead stores is
      the relevant parameter for predicting the level of neurotoxicity of this metal
      gives some optimism for the future: if we study children whose mothers never
      underwent high environmental pollution (born after the withdrawal of lead from
      gasoline) and hence have relatively low bone lead stores we could find that, at
      the population level, lead has little influence on children IQ scores.

PMID- 17000570
TI  - Cadmium and children: exposure and health effects.
AB  - Cadmium exposure and accumulation in the body start at young age. Exposure routes
      in children are mainly via food, environmental tobacco smoke and house dust.
      Excretion from the body is limited. Cadmium accumulation in the kidney is
      responsible for effects such as nephrotoxicity and osteoporosis which are
      observed at adult age. Cadmium exposure through inhalation is also associated
      with lung cancer in adulthood. Although transfer to the neonate through the
      placenta and through breast milk is limited, teratogenic and developmental
      effects were observed in experimental animals. The database on human studies
      involving children is limited, yet effects on motoric and perceptual behaviour in
      children have been associated with elevated in utero cadmium exposure. In school
      age children urinary cadmium levels were associated with immune suppressive
      effects. More studies are needed to confirm these results. Experimental data in
      vitro and in animals refer to effects of cadmium on the hypothalamus-pituitary
      axis at different levels. This may lead to disorders of the endocrine and/or
      immune system. Cadmium exposure at early age should be limited as much as
      possible to prevent direct effects on children and to prevent accumulation of
      cadmium which may have serious health effects only becoming manifest at older
      age.

PMID- 17000571
TI  - The effects of PCBs and dioxins on child health.
AB  - BACKGROUND/EXPOSURE: Dioxins and PCBs are highly persistent and highly toxic
      environmental pollutants which at present are derived mainly from waste
      incineration and food contamination. They are widespread in nature and pollute
      human food, including breast milk so that basically all children in Europe are
      exposed to measurable levels. RESULTS/TOXICITY IN CHILDREN: The toxicity of
      dioxins and PCBs are well described both from animal studies and from a number of
      human epidemiological studies including several large cohort studies. Especially
      developmental exposure has been shown to affect endocrine and cognitive systems
      negatively. Measurable outcomes include reduced IQ and changed behaviour.
      Foetotoxic effects with reduced birth weight and increased congenital anomalies
      such as cleft lip have also been described. Exposure to PCBs and dioxins must be
      considered also in the context of multiple exposure to several toxins
      simultaneously or sequentially. CONCLUSION/SUGGESTED ACTION: Some measures aimed
      at reducing exposure to dioxins have been partly successful in that the dioxin
      content of breast milk is going down. However, further steps to reduce exposure
      must be taken. We suggest legislative measures for reducing the re-entry of
      especially PCBs from waste into the environment. Individual pre-conception
      counselling is recommended in order to reduce developmental exposure and its
      consequences. Biomonitoring of the substances themselves in breast milk and foods
      is recommended as well as monitoring possible endocrine effects.

PMID- 17000572
TI  - Children's exposure to polybrominated diphenyl ethers.
AB  - BACKGROUND: Polybrominated biphenyl ethers (PBDEs), a class of brominated flame
      retardants, are frequently used in consumer products. PBDEs levels in
      environmental and human samples have increased in recent decades. Children are
      exposed to PBDEs through diet, mainly through fish, meat and milk. Total dietary
      exposure of children in Europe was calculated to be 2-3 ng/kg b.w./day. For
      nursing infants the main source of PBDE exposure is breast milk; exposure levels
      are around 15 ng/kg b.w./day. PBDE exposure levels in North America are 10 to a
      100 times higher. Because of their persistence and their similarity to
      polychlorinated biphenyls (PCBs), concern has been raised about the effects of
      PBDEs on human health. Exposure to penta- and octa-BDE led to learning impairment
      and impaired motor behaviour in rodents. Exposure to penta-, octa- and also deca
      BDE caused effects on thyroid homeostasis in animals. CONCLUSIONS: The EU has
      banned the production and use of penta- and octa-BDE since 2004; however,
      exposure will continue during the coming decades. Based upon current
      toxicological evidence, human exposure to deca-BDEs is not expected to lead to
      health effects, but data on exposure to deca-BDE and data on toxicity of deca-BDE
      are scarce. Therefore, monitoring studies and toxicity studies on deca-BDEs and
      other BDEs should continue.

PMID- 17000573
TI  - Adverse health effects of children's exposure to pesticides: what do we really
      know and what can be done about it.
AB  - Children may be exposed to pesticides in several ways, such as by transplacental
      transfer during foetal life, by intake of contaminated breast milk and other
      nutrients, or by contact with contaminated subjects and areas in the environment
      such as pets treated with insecticides, house dust, carpets and chemically
      treated lawns and gardens. Exposure early in life, and particularly during
      periods of rapid development, such as during foetal life and infancy, may have
      severe effects on child health and development by elevating the risk of
      congenital malformations, cancer, malabsorption, immunological dysfunction,
      endocrine disease, and neurobehavioural deficiencies. As pesticides can also
      interfere with parental reproductive health, exposure of parents may have
      consequences for the offspring leading to reduced chance of male birth and
      increased risk of childhood cancer. CONCLUSIONS: Current knowledge about
      tolerable levels and consequences of toxic exposure to pesticides during human
      development is rather scarce. Owing to the high risk of exposure to pesticides,
      particularly in less developed countries, further elucidation by well-controlled
      epidemiological studies in this field it is urgently needed. The Policy
      Interpretation Network on Children's Health and Environment (PINCHE), which is
      financed by the EU DG research has suggested actions against pesticide exposure.
      They have been presented and discussed in this paper. Several suggestions of
      PINCHE concerning action needed regarding pesticides were presented in the paper.

PMID- 17000574
TI  - Ionizing radiation and children's health: conclusions.

PMID- 17000575
TI  - Environmental tobacco smoke exposure and children's health.
AB  - Almost half of the child population is involuntarily exposed to environmental
      tobacco smoke (ETS). The ETS exposure gives rise to an excessive risk of several
      diseases in infancy and childhood, including sudden infant death syndrome, upper
      and lower respiratory infections, asthma and middle ear diseases. It is also
      linked to cancer, and behavioural problems and neurocognitive deficits in
      children. CONCLUSIONS: Protecting children from ETS exposure is a complex and
      important issue. The best improvement in children's health is to be gained when
      parents stop smoking or, when that is not possible, they stop smoking in their
      children's environment. Paediatricians, because of their authority, and their
      frequent and regular contact with parents, play a leading role in protecting
      children from ETS exposure. An ideal approach to help parents to stop smoking
      seems to be initial minimal-contact advice provided by their paediatrician with
      feedback and supplemental printed materials, leading to greater intensity and
      duration of follow-up home visits.

PMID- 17000576
TI  - Air pollution: a threat to the health of our children.
AB  - BACKGROUND/METHODS: Current air pollution levels pose a threat to the health of
      children starting from conception. The scientific evidence is presented for
      mortality, morbidity, and sub-clinical effects. The first section deals with
      exposure data, the following sections with the evidence of health effects from
      epidemiology and toxicology leading to recommendations. RESULTS: Improved air
      quality reduces the number of infants' deaths as well as disease and pain.
      CONCLUSIONS: Medical doctors have a responsibility to know the facts and to
      advise their patients. Doctors when visiting their patients' homes should be
      aware of the possibly grave impact of the indoor environment for the respiratory
      health of their patients. They should recognize and advise the parents on
      problems associated with environmental tobacco smoke, poor ventilation, mould
      growth, and maintenance of heating installations. With regard to outdoor air
      pollution, doctors could serve as role models and also advise their patients and
      parents on environmentally friendly behaviour. Such behaviour not only calls for
      personal commitment but also for the right infrastructure to be provided (e.g.
      public transport, district heating). Doctors should be proactive in the community
      and in their country as advocates for a healthier environment for our children.

PMID- 17000577
TI  - Exposure to multiple environmental agents and their effect.
AB  - INTRODUCTION: All children are exposed to multiple physical, chemical and
      biological challenges that can result in adverse health effects before and after
      birth. In this context, the danger of multiple exposures cannot be assessed from
      a single-chemical approach as used in classical toxicology. AIM: To open up a
      'negotiation space' for the problem of multiple exposure to environmental
      stressors, defined as any physical, chemical or biological entity that can induce
      an adverse response. In this context, two further questions obtain: to what
      extent can synergistic risks be assessed, and how far could potential adverse
      effects be prevented by enhanced regulation? METHODS: A discussion of two general
      approaches is taken: 1) the investigation of mixtures such as smoking or air
      pollution without specifying the individual agents, and 2) the investigation of
      individual substances with a focus on possible interactions in the context of
      dose to receptor. RESULTS: Although mixtures of compounds can have effects, it
      may not be possible to ascribe causation to a single compound. Furthermore,
      cumulative low-dose insult can, in some circumstances, be more toxic than a
      single high-dose exposure, e.g. endocrine disruptive effects of a combination of
      PCBs and dioxins which disrupt the thyroid hormone status; this tends to
      contradict elements of classical toxicology, . These cumulative insults may
      further combine with heavy metals and can disrupt the heme synthesis. It is
      possible that groups of pollutants could be used to test their cumulative
      capacity to multiple stress-susceptible receptor targets as is done in smoking
      and air pollution. This methodology could be used for further groups of potential
      pollutants, for example those associated with cleaning products, or cosmetics.
      Testing individual substances with a focus on interactions means that not only
      chemicals but also concurrent diseases should be taken into account. We suggest
      that the enhanced regulation of potential multiple stressors falls into two
      discrete categories. The first comprises a more precautionary approach (as
      demonstrated by the banning of chemicals such as some brominated flame retardants
      in Europe). The second comprises a more 'permissive' liberal approach involving
      the initial study of an individual compound, and subsequent interrogation of that
      compound in combination with another (as demonstrated by lowering the
      carcinogenicity of aflatoxin by vaccination against hepatitis B). CONCLUSIONS: It
      is necessary to define and study groups of multiple stressors as in US EPA's
      Framework for Cumulative Risk Assessment (U.S. EPA 2003). Recent increased
      knowledge of the greater sensitivity of the unborn baby, the infant and the
      child, has led to general recognition that a higher degree of precaution is now
      needed in regulating for multiple stressors on the young. The more liberal
      permissive approach proceeding from established effects of the individual
      exposures is becoming less acceptable now that we know that there is much we do
      not understand about chronic effects of stressors during the early development
      phases. Conflicts over which approach to take may have to be resolved through
      engagement and negotiation with a wide community of stakeholders. This "community
      of interest" may include fundamental research scientists, practicing clinical
      paediatricians, patient groups, and others concerned with the health and
      wellbeing of infants and children.

PMID- 17000578
TI  - Policy and science in children's health and environment: recommendations from the
      PINCHE project.
AB  - BACKGROUND: Policy recommendations result from the discussions and analysis of
      the present situation in environment and health. Such analysis was performed in
      PINCHE. This led to recommendations based on the scientific literature. In the
      field of children's environmental health the policy process will follow more or
      less fixed rules, but this process is still at an early level of development. The
      link between science and policy still faces many challenges. Scientific
      assessment of environmental risk must recognize and tackle the problems of data
      sets, variability of human and environmental systems, the range, spatial and
      temporal diffusion of potential health effects and many biases and confounding
      factors. RESULTS: The PINCHE network recommends a general improvement of the
      supporting scientific fields in environment and health. Assessments from
      epidemiology or toxicology should play a key role in influencing science-policy
      decisions in programmes that are intended to inform the public policy process.
      Scientific committees at a local level could play a role. The relation between
      health and environment needs to be better incorporated in training and education.
      There is a need for harmonization of data production and use. The priorities in
      PINCHE focus on the most important issues. A classification of low, medium or
      high priority for action was used to describe a range of different environmental
      stressors. CONCLUSIONS: PINCHE provided recommendations to reduce exposure for
      children. Exposure reduction is not always linked to improved health in the short
      term, but it will reduce the body burden of accumulating chemicals in children. A
      strategic choice is reduction of exposure of children to compounds by changing
      production techniques or by increasing the distance of child specific settings to
      sources. The contribution of all players in the production, distribution and use
      of scientific knowledge in the field of children's environmental health is
      necessary.

PMID- 17000579
TI  - Is endometrial monitoring required with the use of long-term unopposed vaginal
      estrogen?

PMID- 17000580
TI  - Lessons from RUTH.
AB  - The Raloxifene Use for The Heart (RUTH) trial was designed to investigate
      possible cardioprotective effects of raloxifene in elderly women with coronary
      artery disease (CAD) or at risk for CAD. While RUTH results demonstrated a
      neutral effect on CAD risk during 5.6 years of follow-up, they also open a debate
      whether primary prevention of fractures or breast cancer by raloxifene is
      justified in view of the serious adverse events which were recorded in this
      trial. Furthermore, the absolute numbers of saved events (breast cancer and
      clinical vertebral fractures) or added events (stroke and venous thromboembolism)
      were in the order of only 1 case per 1,000 treated women/year, a figure which
      should be evaluated on a pharmacoeconomic scale as well.

PMID- 17000581
TI  - Hormone replacement therapy in women with past history of endometriosis.
AB  - Endometriosis is a common clinical condition and its treatment will often lead to
      an estrogen deficiency status. As most of these patients are young, they will
      need to consider hormone replacement therapy. Endometriosis is a hormone
      dependent disease and estrogen replacement can be associated with a risk of
      recurrence or malignant transformation. Only a few studies have addressed this
      problem. With the use of hormone replacement therapy (HRT), there is an
      increased, although undefined, risk of recurrence of endometriosis, especially in
      known severe cases and in obese patients. Unopposed estrogen appears to carry a
      higher risk than combined preparations. Delay in starting HRT after pelvic
      clearance is not of any benefit. After radical surgery for severe endometriosis,
      women often have much to gain from HRT, particularly in the early years. Benefits
      of HRT in terms of control of menopausal symptoms, prevention of urogenital
      atrophy and loss of libido and bone protection are of particular importance. HRT
      may still have a role in prevention of cardiovascular disease in early menopause,
      but this remains unproven. Although there is no firm evidence, continuous
      combined preparations or tibolone would appear to be the optimum choice.

PMID- 17000582
TI  - Factors associated with the use of complementary medicine and non-pharmacological
      interventions in symptomatic menopausal women.
AB  - BACKGROUND: Hormone replacement therapy is now thought to have serious adverse
      effects; consequently, many menopausal women are seeking to use complementary and
      alternative medicine (CAM), including non-pharmacological interventions (NPI), to
      alleviate symptoms. The prevalence and perceived effectiveness of CAM and NPI for
      ameliorating menopausal symptoms are not widely known and factors likely to
      predict CAM and NPI utilization for menopausal symptom management have not been
      comprehensively documented. OBJECTIVES: The objectives of this study were to (1)
      determine the prevalence of using CAM and NPI for menopausal symptoms; (2)
      describe the perceived effectiveness of CAM and NPI for symptom management; and
      (3) investigate lifestyle and demographic factors associated with CAM/NPI use
      among menopausal women with vasomotor symptoms. METHODS: Women aged 46-55 years
      were recruited via six socioeconomically diverse general practices. Participants
      completed a postal questionnaire that contained items relating to demographics,
      lifestyle factors, weight, height, exercise behavior, menopausal status,
      vasomotor symptoms and utilization and perceived effectiveness of a range of
      CAM/NPI for symptom management. RESULTS: Of 1,206 women who responded, 563 (47%)
      were symptomatic. The most commonly used CAM/NPI for symptom management were
      diet/nutrition (44.3%), exercise/yoga (41.5%), relaxation/stress management
      (27.4%) and homeopathic/naturopathic remedies (25.4%). Of women who used these
      interventions, large proportions reported them to be helpful. The characteristics
      that were independently associated with use of CAM/NPI were White ethnicity,
      being physically active, and not smoking. CONCLUSIONS: Many menopausal
      symptomatic women are using a wide range of CAM/NPI and report these to be
      effective, particularly those who are white, physically active and do not smoke.

PMID- 17000583
TI  - Risk communication in consultations about hormone therapy in the menopause:
      concordance in risk assessment and framing due to the context.
AB  - BACKGROUND: It is important for the physician and the patient to have a mutual
      understanding of the possible consequences of different treatment alternatives in
      order to achieve a partnership in decision-making. OBJECTIVE: The aim of this
      study was to explore to which degree first-time consultations for discussion of
      climacteric discomfort achieved shared understanding of the risks and benefits
      associated with hormone therapy in the menopausal transition. METHODS: Analysis
      of structure and content of transcribed consultations (n = 20), and follow-up
      interviews of the women (n = 19 pairs of consultations and interviews), from
      first-time visits for discussion of climacteric discomfort and/or HT with five
      physicians at three different outpatient clinics of gynecology in Sweden.
      RESULTS: Four distinctively different interpretations of risk, depending on
      whether or not benefits were discussed in the same context, emerged from the
      analysis. On average, five advantages (range 0-11) and two (0-3) disadvantages
      were mentioned during the consultations. In the interviews, the women expressed
      on average four advantages (0-7) and one disadvantage (0-3). There were major
      variations between advantages and disadvantages expressed in the consultation and
      the following interview. CONCLUSION: Even though the consultations scored high in
      patient involvement, the information in most consultations was not structured in
      a way that made it possible to achieve a shared or an informed decision-taking.

PMID- 17000584
TI  - Factors affecting sexuality in older Australian women: sexual interest, sexual
      arousal, relationships and sexual distress in older Australian women.
AB  - OBJECTIVE: To investigate the sexual behavior, sexual relationships, sexual
      satisfaction, sexual dysfunction and sexual distress in a population of older
      urban Australian women. METHOD: In 2004, 474 women participating in the
      Longitudinal Assessment of Ageing in Women (LAW) Study completed a series of
      questionnaires about sexuality. They included the Short Personal Experiences
      Questionnaire (SPEQ), Relationship Assessment Scale (RAS), Female Sexual Distress
      Scale (FSDS), questions concerning past sexual abuse based on the Sex in
      Australia Study, and questions comparing present and past sexual interest and
      activity. RESULTS: The percentage of women with partners ranged from 83.3% in the
      40 - 49-year age group to 46.4% women in the 70 - 79-year age group. The sexual
      ability of partners diminished markedly with age, with only 4.8% of the partners
      using medication to enable erections. Only 2.5% of women reported low
      relationship satisfaction. The incidence of sexual distress was also low, being
      reported by only 5.7% of women. Younger women and women with partners had higher
      levels of distress than older women. Indifference to sexual frequency rose from
      26.7% in women aged 40 - 49 years to 72.3% in the 70 - 79-year age group. Past
      sexual abuse was recalled by 22.7% of women and 11.6% recalled multiple episodes
      of abuse. Women who recalled abuse had lower scores for satisfaction with sexual
      frequency. CONCLUSIONS: It appears from this study that there is a wide range of
      sexual experience amongst aging women, from never having had a sexual partner, to
      having solitary sex, to having a relationship with or without sex into the
      seventh decade. As women age, they experience a decrease in sexual activity,
      interest in sex, and distress about sex. This may be associated with the loss of
      intimate relationships as part of separation, divorce or bereavement. Decreased
      sexual activity with aging may be interpreted as a biological phenomenon (part of
      the aging process) or as sexual dysfunction, or it may be the result of adapting
      to changed circumstances.

PMID- 17000585
TI  - The dilemma of menopause and hormone replacement--a challenge for women and
      health-care providers: knowledge of menopause and hormone therapy in Spanish
      menopausal women.
AB  - BACKGROUND: An important goal in menopause research is to develop knowledge and
      identify interventions that strive to promote, maintain and enhance well-being
      for women. OBJECTIVE: To evaluate the knowledge of postmenopausal Spanish women
      about menopause and their knowledge of and trust in hormone replacement therapy
      (HRT) and to identify their sources of information and how those data are related
      to compliance with their prescription. STUDY DESIGN: A total of 270 symptomatic
      postmenopausal women were personally interviewed using a structured
      questionnaire, which was designed to collect information on their familiarity
      with medical menopause studies, the menopause and the effects of HRT, their
      knowledge of alternative therapies, and to identify their sources of information.
      RESULTS: The most well-known menopausal complaints were hot flushes, sweats,
      irregular menstruation, cessation of menstruation, irritability and mood changes.
      Following suggestions of other symptoms by the interviewer, other complaints such
      as vaginal dryness, insomnia and depression/anxiety were also mentioned. HRT and
      phytoestrogens were recognized as treatments for the climacteric by most of the
      women. A woman's decision to seek treatment was initiated in 77% of cases by the
      gynecologist, in 12% by the general practitioner, in 3% by friends/family and in
      3% by books/magazines. The most frequent responses of women to the onset of
      menopausal symptoms were to talk with their partner (39%), to discuss it with
      their gynecologist (33%) or with their general practitioner (14%) and to talk
      with their friends/family or to read books/magazines (10%). CONCLUSIONS:
      Vasomotor symptoms are recognized as the main complaint during the climacteric
      and HRT and phytoestrogens as the main therapies. Gynecologists play an important
      role in assuring compliance with therapies related to the menopause.

PMID- 17000586
TI  - Effects of low- or high-dose hormone therapy on fasting and post-methionine
      homocysteine levels in postmenopausal women.
AB  - OBJECTIVE: To evaluate the effect of two different hormone therapy (HT) doses on
      fasting and post-methionine homocysteine levels, an independent risk factor for
      cardiovascular and thromboembolic diseases. METHODS: Forty-eight women in natural
      postmenopause randomly received calcium 1 mg/day (control group; n = 12) or
      calcium plus low dose (1 mg estradiol plus 0.5 mg norethisterone; n = 18) or high
      dose (2 mg estradiol plus 1 mg norethisterone; n = 18) HT in a 6-month
      randomized, controlled, prospective study. RESULTS: Folate levels did not vary in
      any group, while levels of vitamin B12 significantly decreased after low- (-12.2
      +/- 6.6%; p < 0.04) or high-dose HT (-13.9 +/- 6.1%; p < 0.01). Fasting
      homocysteine was reduced by either HT dose in a way that was inversely related to
      pretreatment homocysteine levels (-0.675x; r = 0.644; p < 0.0001). Modification
      of post-load homocysteine increase was influenced by the HT dose and inversely
      related to the homocysteine response to methionine observed at baseline. The
      regression slope observed with the low-dose HT (-1.637x; r = 0.57; p < 0.02) was
      significantly steeper (p < 0.001) than that observed with the high-dose HT (
      0.304x; r = 0.554; p < 0.03) dose. CONCLUSIONS: Low- or high-dose HT similarly
      influences fasting homocysteine levels. Low-dose HT seems to be more effective
      than high-dose HT in reducing the post-methionine homocysteine increase.

PMID- 17000587
TI  - Response to commentaries on retention of the ovaries and long-term survival after
      hysterectomy.

PMID- 17000589
TI  - An atypical presentation of visual hallucinatory experiences following prolonged
      blindness.
AB  - We report a patient with long-standing blindness experiencing both simple and
      complex visual hallucinations secondary to a cortical arteriovenous malformation
      (AVM). The hallucinations were located in the right visual field corresponding to
      the contra-lateral site of cortical damage. This case contributes to our
      understanding of neurophysiological mechanisms underlying visual hallucinations
      and ongoing research investigating the phenomenology of hallucinations with
      respect to the cause and localization of neural damage.

PMID- 17000588
TI  - Ipsilesional attentional-approach neglect or crossover effect.
AB  - Patients with ipsilateral neglect (IN) bisect lines toward contralesional space.
      It has been posited that IN might be induced by an attempt at compensation, as
      part of the crossover effect, where patients with an ipsilesional bias when
      bisecting long lines, cross over and develop a contralesional bias on short lines
      or as a release of an approach (grasp) behavior that might be attentional or
      intentional. To test these alternative hypotheses we had a patient with IN from a
      right medial frontal lesion bisect lines that contained no cue, a left-sided cue,
      a right-sided cue, and bilateral cues. If this patient had ipsilateral neglect
      (IN) because of a crossover effect or compensation, right-sided cues should have
      influenced bisection more than left-sided cues. We, however, found that only left
      sided cues induced a significant change (left-sided deviation) providing support
      for the attentional-approach (grasp) hypothesis. Further support of this
      contralesional attentional grasp hypothesis comes from the observation that this
      patient also had ipsilesional extinction to simultaneous stimuli.

PMID- 17000590
TI  - Acute and long-term VNS effects on pain perception in a case of treatment
      resistant depression.
AB  - Vagus Nerve Stimulation (VNS) is approved by the FDA for treatment of both
      epilepsy and depression. Recent work has shown that VNS acutely affects pain
      perception in humans, actually increasing pain sensitivity momentarily while the
      device is firing. It is unclear how this acutely increased sensitivity might
      change over time with treatment and how it might relate to longer-term
      therapeutic effects of VNS on pain. We describe a patient with treatment
      resistant depression and a history of severe lumbar degenerative disease with
      resultant chronic low back pain. His depression and pain symptoms both seemed to
      respond to VNS. He eventually stopped all medications and remained depression and
      pain free for 35 months with no change in his device settings. Sixty-six months
      after VNS implantation and 64 months after his initial clinical antidepressant
      response, under single-blind conditions, we performed quantitative sensory
      testing with laboratory thermal pain procedures during acute VNS-on and -off
      conditions. Interestingly, despite a significant and profound anti-nociceptive
      clinical response for the previous 35 months, he had significant increases in
      painfulness ratings while the VNS device was actively firing compared with device
      off conditions. This case suggests that VNS-induced acute increases in pain
      sensitivity can coexist with a clinical anti-nociceptive response. If the acutely
      increased sensitivity sets the stage for the slower chronic anti-pain effects,
      the increased acute sensitivity does not disappear. Acute and chronic effects of
      VNS on pain perception merit further research.

PMID- 17000591
TI  - Progressive oculo-orofacial-speech apraxia (POOSA).
AB  - A loss of speech can be related to disorders of the motor units (paresis),
      language deficits (aphasia), or speech programming deficits (apraxia of speech).
      Although apraxia of speech has been reported to be associated with degenerative
      diseases, we observed a patient with a unique constellation of signs that
      included apraxia of speech, oculo-orofacial apraxia and a supranuclear
      ophthalmoplegia in the absence of extrapyramidal (Parkinsonian) signs. Post
      mortem examination revealed a loss of neurons in the frontal and temporal
      regions, but there was also a marked loss of neurons and astrogliosis in the
      caudate, claustrum, globus pallidus, substantia nigra, and loss of axons in the
      anterior cerebral peduncles. This patient's clinical presentation and the
      pathological correlates suggest that he might have suffered with a distinct
      disorder we call progressive oculo-orofacial-speech apraxia or POOSA.

PMID- 17000592
TI  - The effect of auditory stressors on cognitive flexibility.
AB  - Stress is known to activate the noradrenergic system which may have a modulatory
      influence on cognitive flexibility. We investigated whether an auditory stressor
      would thus affect performance on cognitive flexibility. A task utilizing
      cognitive flexibility and two memory tasks were presented in both stressful and
      non-stressful condition. In the stressful condition performance was impaired for
      the cognitive flexibility task but not for the memory tasks, arguing against the
      stressor serving as a general distracter. These findings suggest that stress
      caused by an auditory stressor may negatively impact performance on more complex
      tasks requiring a rapid search of the semantic and lexical associative networks.

PMID- 17000593
TI  - Dysfunction of a structurally normal motor pathway in a brain injury patient as
      revealed by multimodal integrated techniques.
AB  - We report on a patient with left hemiparesis and peripersonal neglect after post
      traumatic left frontal hemorrhage, who underwent fMRI, TMS and TCD to identify
      the functional abnormalities that account for his neurological symptoms, in the
      absence of any detectable lesion affecting right motor areas.

PMID- 17000595
TI  - The scale for emotional blunting in patients with frontotemporal dementia.
AB  - Emotional blunting may underlie many of the behavioral features of frontotemporal
      dementia (FTD). The Scale for Emotional Blunting (SEB) was evaluated in 12
      patients with early FTD, 12 patients with Alzheimer's disease (AD), and 12 normal
      controls. There were overall group differences on the SEB, and the FTD patients
      had greater emotional blunting than the AD patients. The SEB had good inter-rater
      reliability and a sensitivity of 92%, and a specificity of 83.5% for FTD. These
      findings suggest that the SEB may be a good instrument for the early detection
      and quantification of emotional blunting in patient with FTD.

PMID- 17000596
TI  - Decision-making after traumatic brain injury in children: a preliminary study.
AB  - Decision-making under conditions of uncertainty was studied in 11 children with
      moderate to severe post-acute traumatic brain injury (TBI) using a modification
      of the Iowa Gambling Task (Bechara et al., 1994). We hypothesized that decision
      making would be compromised in children with TBI. The results revealed that when
      divided into subgroups by lesion location, children with lesions in the amygdala
      (AM) were impaired on modified gambling task performance, but children with
      ventromedial (VM) lesions did not appear to be impaired on the task. These
      results are in contrast to studies of decision-making in adults with focal
      lesions of vascular etiology.

PMID- 17000597
TI  - Acquired dyslexia after stroke in the prereading stage: a single case treatment
      study with f MRI.
AB  - The authors report a treatment study of a child (CK) who suffered a left
      hemisphere stroke at age 6.3 years, a few months before beginning school. Despite
      complete recovery of spoken language abilities, CK failed to acquire written
      language abilities. Neurolinguistic assessment 2 years after the stroke revealed
      marked impairments in working memory, deficits in acquiring a sublexical reading
      strategy, and a very rudimentary orthographic network. Functional imaging
      demonstrated activation in posterior language areas during reading of familiar
      words while the attempt to read unfamiliar words activated peri- and
      contralesional structures of the anterior language areas. It was assumed that
      despite sufficient neural plasticity, the acquisition of a sublexical reading
      strategy was prevented by severe working memory deficits. Therefore, a specific
      treatment intervention was developed, choosing a compensatory strategy for
      reading remediation. Reading development was monitored over three months before
      and three months after an intensive training was conducted. Data showed
      significant gains in reading performance only after the specific intervention.
      These gains remained stable in a catamnesis 2 years later.

PMID- 17000598
TI  - Community action research: an introduction.

PMID- 17000599
TI  - Issues facing the dissemination of prevention programs: three decades of research
      on the adolescent diversion project.
AB  - This paper argues that the issues facing effective prevention programs when they
      embark on dissemination, implementation, and routinization have been largely
      ignored by the field. Through the example of the Adolescent Diversion Program,
      these issues are illustrated and discussed. Four sequential longitudinal
      experimental studies are summarized as a context for the discussion of
      dissemination issues. In each case, the alternative preventive program is
      demonstrated to be more effective than traditional approaches. Challenges to
      widespread implementation of effective prevention programs are then discussed
      with a call for the field to add such issues to its scientific agenda.

PMID- 17000600
TI  - Assessment of home-based behavior modification programs for autistic children:
      reliability and validity of the behavioral summarized evaluation.
AB  - Since the publication of Lovaas' (1987) impressive findings, there has been a
      proliferation of home-based behavior modification programs for autistic children.
      Parents and other paraprofessionals often play key roles in the implementation
      and monitoring of these programs. The Behavioral Summarized Evaluation (BSE) was
      developed for professionals and paraprofessionals to use in assessing the
      severity of autistic symptoms over the course of treatment. This paper examined
      the psychometric properties of the BSE (inter-item consistency, factorial
      composition, convergent validity, and sensitivity to parents' perceptions of
      symptom change over time) when used by parents of autistic youngsters undergoing
      home-based intervention. Recommendations for future research are presented.

PMID- 17000601
TI  - The tools to understand: community as co-researcher on culture-specific
      protective factors for Alaska Natives.
AB  - A collaborative research process engaging Alaska Native communities in the study
      of protective factors in Alaska Native sobriety and the design of a preventative
      intervention using its findings is described. Study 1 was discovery oriented
      qualitative research whose objectives were identification of protective factors
      and development of a heuristic model. Study 2 involved quantitative survey
      methods to develop and test ameasure of protective factors identified by the
      qualitative study. Empirical data from these studies is presented, and the role
      of Alaska Native co-researchers who did not possess specialist research training
      is described in the design and implementation of the study, interpretation of
      findings, and design of the intervention model and tools. Benefits that emerged
      from co-researcher involvement in this process, to the community and to the co
      researchers themselves, are described.

PMID- 17000602
TI  - An evaluation of the effects of neighborhood mobilization on community problems.
AB  - This research examines the outcomes of actions taken by members of a residential
      neighborhood association to revitalize a neighborhood and to make it a safer and
      more secure place to live. This urban neighborhood association initiated a major
      planning process in cooperation with city officials. Residents overwhelmingly
      adopted the plan that included the creation of mini-neighborhoods with a series
      of gates to moderate traffic flow, increase neighborliness, and reduce crime. An
      analysis of official data from police crime reports shows that crime was
      significantly reduced in the neighborhood after the street changes. This
      reduction in crime was maintained even five years later. Telephone interviews
      with neighborhood residents indicated that they perceived reductions in traffic,
      crime, noise and drug offenses for at least five years after the changes. Even
      though neighborhood cohesion did not increase, it appears that the actions
      instigated and promoted by neighborhood association members enhanced the quality
      of life for neighborhood residents.

PMID- 17000603
TI  - Literacy for the community, by the community.
AB  - Literacy is a significant challenge in the U.S. and its territories, especially
      in low income communities where use of English language is non-standard.
      Wedeveloped the Actual Community Empowerment (ACE) Reading program for students
      at risk in such communities. ACE is a small-group tutoring program to support
      fluency, word recognition and decoding, and comprehension at the best pace of
      learning for individual, struggling readers. It has several variations (e.g., for
      different ages, different uses of technology), depending on local needs and
      resources. The program has been successfully implemented in 40 locations from
      Philadelphia to Pohnpei, with a 95% success rate for significant reading
      improvement. ACE tutors are community paraprofessionals or school students with
      backgrounds similar to the children who receive tutoring. In the first major
      section of this paper, the ACE Reading Program is described and empirical
      research demonstrating the benefits of the program for students' literacy is
      reviewed. The second major section presents preliminary qualitative research
      evidence that paraprofessional tutors progress through recognizable stages toward
      increased professionalism. Recommendations for future research are provided.

PMID- 17000604
TI  - The community service self-efficacy scale: further evidence on reliability and
      validity.
AB  - The Community Service Self-Efficacy Scale (CSSES) measures". . . the individual's
      confidence in his or her own ability to make clinically significant contributions
      to the community through service" (Reeb et al., p. 48). Three studies reported in
      this article replicate and extend past CSSES research. With regard to
      reliability, results replicate past research in demonstrating internal
      consistency and temporal consistency. Convergent validity was demonstrated by the
      finding that, as hypothesized, the CSSES correlated moderately with a measure of
      general self-efficacy. As hypothesized, the correlation between the CSSES and a
      measure of social desirability was low in magnitude and non-significant,
      demonstrating discriminant validity. Regarding gender differences, females tended
      to score somewhat higher than males on the CSSES. With respect to construct
      validity, CSSES scores changed in the hypothesized direction in response to an
      intervention. While past CSSES research focused on college students, one study
      reported in this paper shows that the CSSES is useful in studying adolescents,
      including those with psychosocial adjustment problems.

PMID- 17000605
TI  - Community elder-care in Tasmania: examining whether caregivers believe they "make
      a-difference" in an urban and rural island.
AB  - Adult caregivers (n = 184;Mage = 43.9 years old) working at a non-profit,
      eldercare program at five geographically diverse sites located in the self
      contained, island state of Tasmania, Australia, completed a set of self-report
      measures. Results across the five sites indicated that respondents experienced a
      relatively strong sense of self-efficacy toward making a difference in their
      local community. However, there were significant differences (controlling for
      social desirability) when comparing caregivers from rural northern (n = 45) with
      urban southern (n = 139) communities, with rural caregivers claiming stronger
      sense of common mission with others, reciprocal responsibility to help others,
      and caregiver satisfaction, plus lower disharmony with other members and
      caregiver stress in helping the elderly than urban caregivers. Implications
      suggest that community self-efficacy may be high among eldercare staff, but their
      sense of community and caregiving perceptions may reflect geographic differences,
      especially in Tasmania.

PMID- 17000606
TI  - Becoming better health care providers: outcomes of a primary care service
      learning project in medical school.
AB  - Medical educators have begun to embrace service-learning as a method for teaching
      medical students to be more socially responsible, patient-oriented practitioners.
      However, research documenting the learning outcomes of service-learning in
      medical education is limited. In this paper, written documents generated through
      evaluation of a mandatory, structured community service-learning experience were
      analyzed qualitatively to discover the diverse learning outcomes among 24
      students who participated in the experience. Preliminary findings indicate that
      students developed skills and attitudes directly related to competencies of
      concern in most U.S. medical programs. These preliminary findings may help other
      programs articulate learning outcomes for their service-learning programs.
      Further, these preliminary findings may stimulate more systematic research
      (qualitative and quantitative) in this area.

PMID- 17000607
TI  - Student outcomes associated with service-learning in a culturally relevant high
      school program.
AB  - The Hawaiian Studies Program (HSP) integrates the learning of Hawaiian culture
      with more traditional secondary curriculum in science, social studies, and
      English. Students also participate in weekly community service-learning sessions.
      Fifty-five HSP students and 29 peers (who were not involved in the program),
      completed a survey measuring: students' connection to, pride in, and
      responsibility for their community; civic attitudes; and career knowledge and
      preparedness. HSP teachers, community members, and students were also interviewed
      about program outcomes. Compared to other peers, HSP students tended to report
      feeling more connected to their community and school and to agree that they had
      career-related skills. Participants believed that service- learning contributed
      to these outcomes by making connections between school and community life and by
      exposing students to a variety of careers.

PMID- 17000608
TI  - Factors associated with effective contraceptive use among a sample of Latina
      women.
AB  - Unintended pregnancy disproportionately affects Latina women. One factor
      contributing to unintended pregnancy among Latinas is the low rate of
      contraceptive use. This study examined correlates of effective contraceptive use
      among a sample of Latina women (n=202) at increased risk for HIV. In addition to
      traditional intrapersonal variables (i.e., perceived risk of pregnancy,
      motivation to avoid pregnancy), the present study examined the role of the male
      partner and relationship factors (i.e., relationship commitment, duration,
      pregnancy prevention decision-making) on contraceptive use. Participants were
      recruited from clinics and community locations in East Los Angeles and
      administered a 60-minute in-person interview. Multivariate logistic regression
      was used to compare women who consistently used effective contraceptives (36%) to
      women using no method or an ineffective method. Women in relationships of 1 to 2
      years were nearly 3 times more likely to use an effective contraceptive compared
      to women in relationships of less than 1 year (odds ratio (OR)=2.7, 95% CI 1.1,
      6.7). Women were more than twice as likely to use an effective method if they
      reported a high level of involvement in decision-making about whether to use
      contraception (OR=2.3, 95% CI 1.1, 4.7) or had discussed contraception with their
      partner (OR=2.4, 95% CI 1.03, 5.6). This study provides additional information
      about the importance of male partners and relationship factors in contraceptive
      use among Latina women. Efforts to prevent unintended pregnancy need to address
      the role of relationship factors in the sexual risk and protective behaviors of
      Latinas.

PMID- 17000609
TI  - Introducing HPV triage into the English cervical cancer screening program:
      consequences for participation.
AB  - OBJECTIVE: To predict the likely impact of adding human papillomavirus (HPV)
      triage for minor abnormalities on participation in the English cervical cancer
      screening program. METHOD: Contingent valuations of the existing Pap program and
      a possible HPV-augmented screening program, obtained from questionnaires
      completed by 1141 women in east-central England. RESULTS: The value of
      participating in Pap screening was negatively associated with age, positively
      associated with educational level, and positively associated with the level of
      household income. Higher levels of worry about cervical cancer were associated
      with higher valuations of screening. Adding HPV-based triage to the Pap program
      lowered the value of screening participation for only two women, whereas for the
      sample as a whole, it increased the average valuation by about 47 percent.
      Supposedly-negative characteristics of HPV testing, when described, were expected
      to trigger psychosocial concerns in respondents and thereby give rise to
      significant decreases in valuations of participating in a Pap-plus-HPV program.
      For most women, however, such information changed their valuations of
      participation in screening little, if at all. CONCLUSIONS: Accepting the
      proposition that higher contingent valuations indicate stronger behavioural
      preferences, our results offer insubstantial grounds for believing that the
      inclusion of HPV triage would detrimentally affect participation in Pap screening
      for cervical cancer.

PMID- 17000610
TI  - Women, mental health and health-related quality of life in coronary patients.
AB  - OBJECTIVE: To establish clusters of Health-Related Quality of Life (HRQL) in a
      population of patients hospitalised for suspected Coronary Heart Disease (CHD),
      and to examine the relationship between mental health and other sociodemographic
      and clinical variables associated with worse HRQL. METHODS: We conducted a cross
      sectional study of 185 patients admitted to the Cardiology Service. We used the
      General Health Questionnaire (GHQ-28) to assess the mental status, and the SF-36
      to assess Health Related Quality Life (HRQL). Using the patients' scores obtained
      from the SF-36, we performed a cluster analysis and used a logistic model for the
      analysis of the variables associated with HRQL clusters. RESULTS: We identified
      two HRQL clusters: good quality of life, for which the patients scored highest in
      all the dimensions of SF-36, and worse quality of life, for which patients had
      lower scores in all dimensions. The variables associated with the worse quality
      of life group were: female gender, previous history of Coronary Heart Disease
      (CHD), and poor mental health. CONCLUSIONS: Being female, having poor mental
      health and a previous history of CHD were identified as representing a vulnerable
      group with worse HRQL.

PMID- 17000611
TI  - Health-promoting behaviors through pregnancy, maternity leave, and return to
      work: effects of role spillover and other correlates.
AB  - Women's health-promoting behavior changes and their correlates across the
      transition to motherhood and return to work are insufficiently understood. The
      purpose of this study was to describe and compare women's health-promoting
      behaviors, particularly physical activity (PA), across these transitions. A
      prospective, observational design was employed to assess 243 female healthcare
      workers from 3 sites with regard to health-promoting behaviors, and their
      demographic (e.g., age, parity) and psychosocial (i.e., work-family role
      spillover) correlates. Forty-two participants were recruited while pregnant and
      re-assessed during maternity leave and upon return to work, and compared to 201
      non-pregnant participants. No significant changes in health-promoting behaviors
      were observed from pregnancy through the postpartum. Pregnant participants
      reported better nutrition than comparison participants (p=.001), and were more
      likely to check their pulse when exercising (p=.004). During pregnancy, health
      promoting behaviors were related to parental status, with first-time mothers
      engaging in more positive behaviors. Correlates of PA during maternity leave and
      return to work included family income and exercise history. Positive family-to
      work spillover was significantly greater among pregnant women than among
      comparison participants (p<.001), and positive work-to-family spillover was
      related to greater PA upon return to work (p<.01). This study reveals little
      variability in health-promoting behaviors from the prenatal to the postpartum
      period. Both demographic and psychosocial factors have effects on health
      promoting behaviors, and we must look to these correlates to promote increased
      PA.

PMID- 17000612
TI  - Cultural similarities and differences between a sample of Black/African and
      colored women in South Africa: convergence of risk related to substance use,
      sexual behavior, and violence.
AB  - South Africa is one of the six southern African countries where the HIV levels
      for childbearing women are 20% or higher. We conducted two focus groups aimed at
      developing an understanding of the intersections of substance abuse, sexual
      behavior, and violence affecting the lives of women of color in Cape Town, South
      Africa. Both Colored and Black/African participants reported using cannabis,
      methaqualone, and alcohol, although they differed on other drugs used.
      Black/African women also used heroin, and crack cocaine, whereas Colored women
      used methamphetamines. For participants in both groups, relationships with men
      affected sexual and substance use risk behaviors. Although the Black/African
      women did not trust men to use condoms, the Colored women in the study believed
      that almost all men use condoms. Both groups of women reported high rates of
      violence, with Colored participants reporting more gang violence and woman-on
      woman violence compared with Black/African participants. The paper discusses
      these issues, as well as the implications for adapting a culturally specific,
      brief woman-focused HIV prevention intervention for the South African context.

PMID- 17000613
TI  - Women's reactions to HPV diagnosis: insights from in-depth interviews.
AB  - Research links certain types of the human papillomavirus (HPV) to subsequent
      development of cervical cancer. Women (n=52) recently diagnosed with HPV
      following an abnormal Pap smear participated in in-depth interviews to explore
      their knowledge of HPV, their emotional responses to diagnosis, and the extent of
      their disclosure of their HPV diagnosis to others. Women had many knowledge
      deficits about HPV. Emotions related primarily to stigma, fear, self-blame,
      powerlessness, and anger. Most women disclosed their disease to significant
      others, usually to a sexual partner. Women's lack of accurate knowledge may
      contribute to the array of emotions they experience. Whereas education about HPV
      may reduce the potency of these emotions, information alone may be inadequate for
      achieving optimal patient care. Health care providers can be important in
      treating the emotional elements associated with diagnosis as well as the
      condition itself.

PMID- 17000616
TI  - The feminization of bereavement among community-dwelling older adults.
AB  - We examined gender differences in frequency and sociodemographic predictors of
      spousal, non-spousal family, and friendship bereavement events among community
      dwelling older adults using data from the UAB Study of Aging. Analysis involved a
      30-month observation period of 893 subjects. There were significant differences
      between women and men for all types of loss. Significant differences were also
      found in the sociodemographic predictors of loss between and within gender
      categories. This study revealed the extent to which older women
      disproportionately bear the burden of loss and points to the need for greater
      attention to bereavement as a women's issue.

PMID- 17000614
TI  - Pregnancy attitudes and contraceptive plans among women entering jail.
AB  - Unplanned pregnancies are an important and costly public health problem. Women
      entering jail are at particularly high risk for unplanned pregnancies when they
      leave jail, given the high rates of poverty, substance abuse and sexually
      transmitted infections (STIs) in this population, all of which are associated
      with unplanned pregnancies. Attitudes toward pregnancy vary substantially,
      influencing openness of incarcerated women to starting a birth control method.
      This study was conducted as part of a Title X service evaluation and examined
      varying attitudes towards pregnancy and associated plans to use contraceptives.
      The current study included 223 women entering jail who were, under 36 years of
      age, fertile, sexually active with men, and not planning to become pregnant in
      the near future. Nearly half of the women had negative pregnancy attitudes (PAs),
      indicating that they did not want to become pregnant, while 41.3% endorsed
      ambivalent PAs. Compared to those with ambivalent PAs, those with Negative PAs
      were more likely to report a previous unplanned pregnancy (90.6% vs. 75.4%), a
      previous pregnancy termination (40.0% vs. 22.8%), and recent consistent use of
      contraceptives (37.0% vs. 21.7%). Women with negative PAs were significantly more
      likely to want to start or to continue a birth control method compared to those
      with ambivalent PAs (66% vs. 47%). Tailoring services to women's specific
      pregnancy attitudes during periods of incarceration may aid in preventing
      unplanned pregnancies in populations of high-risk women.

PMID- 17000617
TI  - Gender differences in body esteem among older adults.
AB  - Ninety-five adults aged 60-91 completed measures of Body-as-Object Esteem (BOE)
      (i.e., appearance) and Body-as-Process Esteem (BPE) (i.e., function) to explore
      gender differences in body esteem among older adults. As hypothesized, a
      significant age by gender interaction revealed that men become more disparaging
      of the appearance and function of their bodies in their last decades of life,
      while women do not. Level of physical disability was negatively correlated with
      BOE, particularly for disabled women. Furthermore, as is seen across the
      lifespan, self-esteem is a significant predictor of BOE. Disabled participants
      who were older than 74 years had disproportionately low BPE scores and similarly
      poor global self-esteem. Whether working with older adults or studying body
      esteem in this population, it is vital that both dimensions of body esteem are
      assessed along with the impact of disability status, gender, self-esteem, and
      age.

PMID- 17000618
TI  - Aging and creating families: Never-married heterosexual women over forty.
AB  - An examination of women over age forty who had never married was conducted. The
      women completed a structured questionnaire about their aging and their self
      esteem was assessed with a standard measure. The participants were women from
      across the United States. Descriptive analyses of the data were ordered with
      ecological systems theory and findings revealed that the women are self
      satisfied, socially productive and well adjusted with their single status and
      that singleness runs in their families. These women have defined what family
      means for them as they age-family of origin and close friendships. This
      description may be helpful in understanding this group as a social force and as
      role models for young women as they age.

PMID- 17000619
TI  - The Red Hat Society: Exploring the role of play, liminality, and communitas in
      older women's lives.
AB  - There is an extensive literature on play. Yet, the role of play in older adults'
      lives has received limited attention. Strikingly absent is research on play and
      older women. Missing from the literature is how older women use play as a liminal
      context for social interaction and communitas. This is odd because by 2030 one in
      four American women will be over the age of sixty-five. The primary purpose of
      this study is to explore the roles of play, liminality, and communitas in older
      women's lives. The focus is the Red Hat Society, a social group for women over
      age 50 that fosters play and fun. Using qualitative interviews with focus groups
      and participant observation of a regional Red Hat Society event, the study
      highlights some of the strengths and weaknesses of current conceptualizations of
      play, liminality, and communitas.

PMID- 17000620
TI  - Self-management of a chronic illness: An exploratory study on the role of
      spirituality among older African American women.
AB  - Living with a chronic illness is an experience characterized by changes in self
      management behavior. Few studies have addressed the role of spirituality in the
      self-management of a chronic illness among older African American women. The
      purpose of this exploratory study was to understand the role of spirituality in
      the self-management of chronic illness. Data from a sample of 10 African American
      women were collected from semi-structured interviews and analyzed for common
      themes through narrative analysis. Four themes emerge from the linkage of
      spirituality and self-management. Understanding this experience will assist
      public health providers in creating culturally appropriate health education
      interventions.

PMID- 17000622
TI  - Exploring the knowledge, attitudes, beliefs, and communication preferences of the
      general public regarding HPV: findings from CDC focus group research and
      implications for practice.
AB  - Genital human papillomavirus (HPV) infection is the most common sexually
      transmitted virus in the United States, causing genital warts, cervical cell
      abnormalities, and cervical cancer in women. To inform HPV education efforts, 35
      focus groups were conducted with members of the general public, stratified by
      gender, race/ethnicity, and urban/rural location. Focus groups explored
      participants' knowledge, attitudes, and beliefs about HPV and a hypothetical HPV
      vaccine as well as their communication preferences for HPV-related educational
      messages. Audience awareness and knowledge of HPV were low across all groups.
      This, along with an apparent STD-associated stigma, served as barriers to
      participants' hypothetical acceptance of a future vaccine. Although information
      about HPV's high prevalence and link to cervical cancer motivated participants to
      learn more about HPV, it also produced audience fear and anxiety. This research
      suggests that HPV- and HPV-vaccine-related education efforts must be approached
      with extreme caution. Other practical implications are discussed.

PMID- 17000623
TI  - Expert consensus document on arterial stiffness: methodological issues and
      clinical applications.
AB  - In recent years, great emphasis has been placed on the role of arterial stiffness
      in the development of cardiovascular diseases. Indeed, the assessment of arterial
      stiffness is increasingly used in the clinical assessment of patients. Although
      several papers have previously addressed the methodological issues concerning the
      various indices of arterial stiffness currently available, and their clinical
      applications, clinicians and researchers still report difficulties in selecting
      the most appropriate methodology for their specific use. This paper summarizes
      the proceedings of several meetings of the European Network for Non-invasive
      Investigation of Large Arteries and is aimed at providing an updated and
      practical overview of the most relevant methodological aspects and clinical
      applications in this area.

PMID- 17000624
TI  - Incidence of syncope after ICD implantation: low or high?

PMID- 17000625
TI  - Redefinition of myocardial infarction: new challenges and opportunities.

PMID- 17000626
TI  - Spontaneous electrocardiographic fluctuations in Brugada syndrome: does it
      matter?

PMID- 17000627
TI  - Inadvertent grafting of the posterior cardiac vein during coronary artery bypass
      graft surgery.

PMID- 17000628
TI  - Right ventricular involvement in Takotsubo cardiomyopathy.
AB  - AIMS: The aim of our study is to assess the incidence and clinical significance
      of right ventricular (RV) involvement in Takotsubo cardiomyopathy (TTC). METHODS
      AND RESULTS: Between February 2002 and December 2005, 47 patients with TTC
      underwent cardiovascular magnetic resonance (CMR) at our institutions. 13
      patients with delayed initial CMR were excluded. In the remaining 34 patients (32
      women), RV wall motion abnormalities (WMAs) were present in nine (26%). Left
      ventricular ejection fraction (LVEF) was significantly lower in patients with RV
      involvement (40 +/- 6 vs. 48 +/- 10%, P = 0.04). The most frequently affected RV
      segments were the apico-lateral (89%), the antero-lateral (67%), and the inferior
      segment (67%). All RV WMA improved or disappeared in eight of nine patients who
      underwent a follow-up CMR study. Pleural effusion was more common in patients
      with RV involvement (67 vs. 8%, P < 0.001) and was predictive of RV dysfunction
      (sensitivity 67% and specificity 92%). Significant or bilateral pleural effusions
      were seen exclusively in patients with RV involvement. CONCLUSION: RV involvement
      is common in TTC and seems to be associated with a more severe impairment in LV
      systolic function. It may be suspected by the presence of pleural effusion.

PMID- 17000629
TI  - Is admission hyperglycaemia in non-diabetic patients with acute myocardial
      infarction a surrogate for previously undiagnosed abnormal glucose tolerance?
AB  - AIMS: To investigate whether admission hyperglycaemia in non-diabetic patients
      with acute myocardial infarction (AMI) is a surrogate for previously undiagnosed
      abnormal glucose tolerance. METHODS AND RESULTS: Two hundred non-diabetic
      patients with AMI were divided into three groups: 81 patients with admission
      glucose < 7.8 mmol/L (group 1), 83 patients with admission glucose > or = 7.8
      mmol/L and < 11.1 mmol/L (group 2), and 36 patients with admission glucose > or =
      11.1 mmol/L (group 3). Abnormal glucose tolerance, diabetes, or impaired glucose
      tolerance (IGT) was diagnosed by oral glucose tolerance test (OGTT). OGTT
      identified diabetes in 53 patients (27%) and IGT in 78 patients (39%). When the
      fasting glucose criteria were applied, however, only 14 patients (7%) were
      diagnosed as having diabetes. The prevalence of abnormal glucose tolerance was
      similar among the three groups: 67% in group 1, 63% in group 2, and 69% in group
      3 (P = 0.74). The relation of fasting glucose (r2 = 0.50, P < 0.001) and HbA1c
      (r2 = 0.34, P < 0.001) to 2-h post-load glucose was significant, but the relation
      of admission glucose to 2-h post-load glucose was not significant (r2 = 0.02, P =
      0.08). Multivariable analysis showed that fasting glucose and HbA1c were
      independent predictors of abnormal glucose tolerance, but admission glucose was
      not. CONCLUSION: Admission hyperglycaemia in non-diabetic patients with AMI does
      not represent previously undiagnosed abnormal glucose tolerance. Fasting glucose
      and HbA1c, rather than admission glucose, may be useful to predict abnormal
      glucose tolerance. However, these parameters lacked sensitivity. OGTT should be
      considered in all non-diabetic patients with AMI.

PMID- 17000630
TI  - The association of impaired myocardial perfusion and monocytosis with late
      recovery of left ventricular function following primary percutaneous coronary
      intervention.

PMID- 17000631
TI  - EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart
      failure patients: description of population.
AB  - AIMS: The objective of the EuroHeart Failure Survey II (EHFS II) was to assess
      patient characteristics, aetiology, treatment, and outcome of acute heart failure
      (AHF) in Europe in relation to the guidelines on the diagnosis and treatment of
      AHF published by the European Society of Cardiology. METHODS AND RESULTS:
      Patients hospitalized for AHF were recruited by 133 centres in 30 European
      countries. Three thousand five hundred and eighty patients were entered into the
      database by the end of August 2005. Mean age was 70 years, and 61% of patients
      were male. New-onset AHF (de novo AHF) was diagnosed in 37%, of which 42% was due
      to acute coronary syndromes (ACS). Clinical classification according to the
      guidelines divided AHF patients into (i) decompensated HF (65%), (ii) pulmonary
      oedema (16%), (iii) HF and hypertension (11%), (iv) cardiogenic shock (4%), and
      (v) right HF (3%). Coronary heart disease, hypertension, and atrial fibrillation
      were the most common underlying conditions. Arrhythmias, valvular dysfunction,
      and ACS were each present as precipitating factor in one-third of cases.
      Preserved left ventricular ejection fraction (> or =45%) was observed in 34%.
      Valvular disorders were common, especially mitral regurgitation (MR) which was
      reported on echocardiography in 80% of patients. Median length of stay was 9
      days, and in-hospital mortality 6.7%. At discharge, 80% of patients were on
      angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers,
      whereas 61% were taking beta-blocker medication. CONCLUSION: Decompensated HF is
      the most common clinical presentation of AHF patients. More than one-third of AHF
      patients do not have a previous history of HF, and new-onset HF is often caused
      by ACS. Preserved systolic function is found in a substantial proportion of the
      patients. The prevalence of valvular dysfunction is strikingly high and
      contributes to the clinical presentation. The EHFS II on AHF verified that the
      use of evidence-based HF medication was well adopted to clinical practice.

PMID- 17000632
TI  - High heart rate: a cardiovascular risk factor?

PMID- 17000633
TI  - Which is the best parameter of submaximal cardiopulmonary exercise testing?

PMID- 17000634
TI  - UKPACE: to die, or not to die ... is that the question?

PMID- 17000635
TI  - Novel rectangular biphasic and monophasic waveforms delivered by a radiofrequency
      powered defibrillator compared with conventional capacitor-based waveforms in
      transvenous cardioversion of atrial fibrillation.
AB  - AIMS: To investigate the feasibility and efficacy of novel low-tilt biphasic
      waveforms in transvenous cardioversion of atrial fibrillation (AF), delivered by
      a radiofrequency-powered defibrillator. METHODS AND RESULTS: The investigation
      was performed in three phases in an animal model of AF: a feasibility and
      efficacy study (in 10 adult Large White Landrace swine), comparison with low-tilt
      monophasic and standard capacitor-based waveforms, and an assessment of
      sequential shocks delivered over several pathways (in 15 adult Suffolk sheep).
      Defibrillation electrodes were positioned transvenously under fluoroscopic
      control in the high lateral right atrium and distal coronary sinus. When multiple
      defibrillation pathways were tested, a third electrode was also attached to the
      lower interatrial septum. The electrodes were then connected to a radiofrequency
      (RF)-powered defibrillator or a standard defibrillator. After confirmation of
      successful induction of sustained AF, defibrillation was attempted. Percentage
      success was calculated from the effects of all shocks delivered to all the
      animals within each set of experiments. Of the low-tilt (RF) biphasic waveforms
      delivered during internal atrial cardioversion, 100% success was achieved with a
      6/6 ms 100/-50 V waveform (1.45+/-0.01 J). This waveform was similar in efficacy
      to low-tilt (RF) monophasic waveforms (88 vs. 92% success, 1.58+/-0.01 vs. 2.67+/
      0.03 J; P=NS; delivered energy 41% lower) and superior to equivalent voltage
      standard monophasic (50% success, 0.67+/-0.00 J; P<0.001) and biphasic waveforms
      (72% success, 0.69+/-0.00 J; P=0.03). Sequential shocks delivered over dual
      pathways did not improve the efficacy of low-tilt biphasic waveforms. CONCLUSION:
      A low-tilt biphasic waveform from a RF-powered defibrillator (6/6 ms 100/-50 V)
      is more efficacious than standard monophasic or biphasic waveforms (equivalent
      voltage) and is similar in efficacy to low-tilt monophasic waveforms.

PMID- 17000636
TI  - Nanoliter high throughput quantitative PCR.
AB  - Understanding biological complexity arising from patterns of gene expression
      requires accurate and precise measurement of RNA levels across large numbers of
      genes simultaneously. Real time PCR (RT-PCR) in a microtiter plate is the
      preferred method for quantitative transcriptional analysis but scaling RT-PCR to
      higher throughputs in this fluidic format is intrinsically limited by cost and
      logistic considerations. Hybridization microarrays measure the transcription of
      many thousands of genes simultaneously yet are limited by low sensitivity,
      dynamic range, accuracy and sample throughput. The hybrid approach described here
      combines the superior accuracy, precision and dynamic range of RT-PCR with the
      parallelism of a microarray in an array of 3072 real time, 33 nl polymerase chain
      reactions (RT-PCRs) the size of a microscope slide. RT-PCR is demonstrated with
      an accuracy and precision equivalent to the same assay in a 384-well microplate
      but in a 64-fold smaller reaction volume, a 24-fold higher analytical throughput
      and a workflow compatible with standard microplate protocols.

PMID- 17000637
TI  - Advancing uracil-excision based cloning towards an ideal technique for cloning
      PCR fragments.
AB  - The largely unused uracil-excision molecular cloning technique has excellent
      features in most aspects compared to other modern cloning techniques. Its
      application has, however, been hampered by incompatibility with proof-reading DNA
      polymerases. We have advanced the technique by identifying PfuCx as a compatible
      proof-reading DNA polymerase and by developing an improved vector design
      strategy. The original features of the technique, namely simplicity, speed, high
      efficiency and low cost are thus combined with high fidelity as well as a
      transparent, simple and flexible vector design. A comprehensive set of vectors
      has been constructed covering a wide range of different applications and their
      functionality has been confirmed.

PMID- 17000638
TI  - A DNA biochip for on-the-spot multiplexed pathogen identification.
AB  - Miniaturized integrated DNA analysis systems have largely been based on a multi
      chamber design with microfluidic control to process the sample sequentially from
      one module to another. This microchip design in connection with optics involved
      hinders the deployment of this technology for point-of-care applications. In this
      work, we demonstrate the implementation of sample preparation, DNA amplification,
      and electrochemical detection in a single silicon and glass-based microchamber
      and its application for the multiplexed detection of Escherichia coli and
      Bacillus subtilis cells. The microdevice has a thin-film heater and temperature
      sensor patterned on the silicon substrate. An array of indium tin oxide (ITO)
      electrodes was constructed within the microchamber as the transduction element.
      Oligonucleotide probes specific to the target amplicons are individually
      positioned at each ITO surface by electrochemical copolymerization of pyrrole and
      pyrrole-probe conjugate. These immobilized probes were stable to the thermal
      cycling process and were highly selective. The DNA-based identification of the
      two model pathogens involved a number of steps including a thermal lysis step,
      magnetic particle-based isolation of the target genomes, asymmetric PCR, and
      electrochemical sequence-specific detection using silver-enhanced gold
      nanoparticles. The microchamber platform described here offers a cost-effective
      and sample-to-answer technology for on-site monitoring of multiple pathogens.

PMID- 17000639
TI  - Replication fork blockage by transcription factor-DNA complexes in Escherichia
      coli.
AB  - All organisms require mechanisms that resuscitate replication forks when they
      break down, reflecting the complex intracellular environments within which DNA
      replication occurs. Here we show that as few as three lac repressor-operator
      complexes block Escherichia coli replication forks in vitro regardless of the
      topological state of the DNA. Blockage with tandem repressor-operator complexes
      was also observed in vivo, demonstrating that replisomes have a limited ability
      to translocate through high affinity protein-DNA complexes. However, cells could
      tolerate tandem repressor-bound operators within the chromosome that were
      sufficient to block all forks in vitro. This discrepancy between in vitro and in
      vivo observations was at least partly explained by the ability of RecA, RecBCD
      and RecG to abrogate the effects of repressor-operator complexes on cell
      viability. However, neither RuvABC nor RecF were needed for normal cell growth in
      the face of such complexes. Holliday junction resolution by RuvABC and
      facilitated loading of RecA by RecF were not therefore critical for tolerance of
      protein-DNA blocks. We conclude that there is a trade-off between efficient
      genome duplication and other aspects of DNA metabolism such as transcriptional
      control, and that recombination enzymes, either directly or indirectly, provide
      the means to tolerate such conflicts.

PMID- 17000640
TI  - Solution structure and functional importance of a conserved RNA hairpin of eel
      LINE UnaL2.
AB  - The eel long interspersed element (LINE) UnaL2 and its partner short interspersed
      element (SINE) share a conserved 3' tail that is critical for their
      retrotransposition. The predicted secondary structure of the conserved 3' tail of
      UnaL2 RNA contains a stem region with a putative internal loop. Deletion of the
      putative internal loop region abolishes UnaL2 mobilization, indicating that this
      putative internal loop is required for UnaL2 retrotransposition; the exact role
      of the putative internal loop in retrotransposition, however, has not been
      elucidated. To establish a structure-based foundation on which to address the
      issue of the putative internal loop function in retrotransposition, we used NMR
      to determine the solution structure of a 36 nt RNA derived from the 3' conserved
      tail of UnaL2. The region forms a compact structure containing a single bulged
      cytidine and a U-U mismatch. The bulge and mismatch region have conformational
      flexibility and molecular dynamics simulation indicate that the entire stem of
      the 3' conserved tail RNA can anisotropically fluctuate at the bulge and mismatch
      region. Our structural and mutational analyses suggest that stem flexibility
      contributes to UnaL2 function and that the bulged cytidine and the U-U mismatch
      are required for efficient retrotransposition.

PMID- 17000641
TI  - Capturing genomic signatures of DNA sequence variation using a standard anonymous
      microarray platform.
AB  - Comparative genomics, using the model organism approach, has provided powerful
      insights into the structure and evolution of whole genomes. Unfortunately, only a
      small fraction of Earth's biodiversity will have its genome sequenced in the
      foreseeable future. Most wild organisms have radically different life histories
      and evolutionary genomics than current model systems. A novel technique is needed
      to expand comparative genomics to a wider range of organisms. Here, we describe a
      novel approach using an anonymous DNA microarray platform that gathers genomic
      samples of sequence variation from any organism. Oligonucleotide probe sequences
      placed on a custom 44 K array were 25 bp long and designed using a simple set of
      criteria to maximize their complexity and dispersion in sequence probability
      space. Using whole genomic samples from three known genomes (mouse, rat and
      human) and one unknown (Gonystylus bancanus), we demonstrate and validate its
      power, reliability, transitivity and sensitivity. Using two separate statistical
      analyses, a large numbers of genomic 'indicator' probes were discovered. The
      construction of a genomic signature database based upon this technique would
      allow virtual comparisons and simple queries could generate optimal subsets of
      markers to be used in large-scale assays, using simple downstream techniques.
      Biologists from a wide range of fields, studying almost any organism, could
      efficiently perform genomic comparisons, at potentially any phylogenetic level
      after performing a small number of standardized DNA microarray hybridizations.
      Possibilities for refining and expanding the approach are discussed.

PMID- 17000643
TI  - Expanding the subproteome of the inner mitochondria using protein separation
      technologies: one- and two-dimensional liquid chromatography and two-dimensional
      gel electrophoresis.
AB  - Currently no single proteomics technology has sufficient analytical power to
      allow for the detection of an entire proteome of an organelle, cell, or tissue.
      One approach that can be used to expand proteome coverage is the use of multiple
      separation technologies especially if there is minimal overlap in the proteins
      observed by the different methods. Using the inner mitochondrial membrane
      subproteome as a model proteome, we compared for the first time the ability of
      three protein separation methods (two-dimensional liquid chromatography using the
      ProteomeLab PF 2D Protein Fractionation System from Beckman Coulter, one
      dimensional reversed phase high performance liquid chromatography, and two
      dimensional gel electrophoresis) to determine the relative overlap in protein
      separation for these technologies. Data from these different methods indicated
      that a strikingly low number of proteins overlapped with less than 24% of
      proteins common between any two technologies and only 7% common among all three
      methods. Utilizing the three technologies allowed the creation of a composite
      database totaling 348 non-redundant proteins. 82% of these proteins had not been
      observed previously in proteomics studies of this subproteome, whereas 44% had
      not been identified in proteomics studies of intact mitochondria. Each protein
      separation method was found to successfully resolve a unique subset of proteins
      with the liquid chromatography methods being more suited for the analysis of
      transmembrane domain proteins and novel protein discovery. We also demonstrated
      that both the one- and two-dimensional LC allowed for the separation of the alpha
      subunit of F1F0 ATP synthase that differed due to a change in pI or
      hydrophobicity.

PMID- 17000644
TI  - Distinct and overlapping sets of SUMO-1 and SUMO-2 target proteins revealed by
      quantitative proteomics.
AB  - The small ubiquitin-like modifier (SUMO) family in vertebrates includes three
      different family members that are conjugated as post-translational modifications
      to target proteins. SUMO-2 and -3 are nearly identical but differ substantially
      from SUMO-1. We used quantitative proteomics to investigate the target protein
      preferences of SUMO-1 and SUMO-2. HeLa cells were established that stably express
      His6-SUMO-1 or His6-SUMO-2. These cell lines and control HeLa cells were labeled
      with stable arginine isotopes, and His6-SUMOs were enriched from lysates using
      immobilized metal affinity chromatography. 53 SUMO-conjugated proteins were
      identified, including 44 novel SUMO targets. 25 proteins were preferentially
      conjugated to SUMO-1, 19 were preferentially conjugated to SUMO-2, and nine
      proteins were conjugated to both SUMO-1 and SUMO-2. SART1 was confirmed by
      immunoblotting to have both SUMO-1- and SUMO-2-linked forms at similar levels.
      SUMO-1 and SUMO-2 are thus shown to have distinct and overlapping sets of target
      proteins, indicating that SUMO-1 and SUMO-2 may have both redundant and non
      redundant cellular functions. Interestingly, 14 of the 25 SUMO-1-conjugated
      proteins contain zinc fingers. Although both SUMO family members play roles in
      many cellular processes, our data show that sumoylation is strongly associated
      with transcription because nearly one-third of the identified target proteins are
      putative transcriptional regulators.

PMID- 17000645
TI  - Proteome analysis of plant-virus interactome: comprehensive data for virus
      multiplication inside their hosts.
AB  - Known host-parasite molecular interactions are widespread among parasite
      families, but these interactions have to be particularly large considering that
      viruses generally encode few proteins. Although some particular virus-host
      interactions are well described, no global study has yet shown multiple and
      simultaneous interactions in a host-parasite biological system. To prove that
      these multiple interactions occur in biological conditions, the complexes formed
      by a plant virus (rice yellow mottle virus) and the proteins of its natural host
      (rice) were extracted and purified from infected tissue sample. Remarkably mass
      spectrometry permitted the identification of a large number of proteins from the
      complexes that are involved in different functions not encoded by the virus but
      probably essential for its biological life cycle. This recruiting of proteins was
      strongly confirmed by the repetition of experiments using different pairs of
      virus-host and the use of high salt concentration to extract the complexes. We
      mainly identified proteins involved in plant defense, metabolism, translation,
      and protein synthesis and some proteins involved in transport. This study
      demonstrates that viruses are able to recruit many proteins from their hosts to
      ensure their development. Among different pairs of virus-host, similar protein
      functions were identified suggesting a particular importance of these proteins
      for viruses. The identification of particular paralog proteins among multigenic
      families suggests the high specificity of the recruiting for some protein
      functions.

PMID- 17000646
TI  - Leukaemia inhibitory factor and interleukin 11 levels in uterine flushings of
      infertile patients with endometriosis.
AB  - BACKGROUND: Exact aetiology of infertility in stage I/II endometriosis patients
      is not known. Interleukin 11 (IL-11) and leukaemia-inhibitory factor (LIF) are
      factors associated with implantation window in human eutopic endometrium. We
      decided to test whether there is an altered secretion of these factors, which
      could explain receptivity defect in patients with minimal endometriosis. METHODS:
      Uterine flushing and endometrial samples were collected 7-9 days after ovulation
      (implantation window) from infertile patients with stage I/II endometriosis (n =
      14) and fertile, endometriosis-free controls (n = 21). IL-11 and LIF were
      assessed in uterine flushings in eutopic endometria in all patients by enzyme
      linked immunosorbent assay (ELISA). In eutopic endometrium, semiquantitative RT
      PCR was performed for LIF and IL-11 mRNA expressions. RESULTS: No statistically
      significant differences were found in uterine flushing in women with and without
      endometriosis with regard to IL-11 levels (0.0 pg/ml versus 0.0 pg/ml) and LIF
      (25.53 pg/ml versus 36.26 pg/ml). These results were confirmed by the results of
      RT-PCR, where there were also no differences between studied groups. CONCLUSIONS:
      There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic
      endometrium in infertile women with endometriosis.

PMID- 17000647
TI  - Both GnRH agonist and continuous oral progestin treatments reduce the expression
      of the tyrosine kinase receptor B and mu-opioid receptor in deep infiltrating
      endometriosis.
AB  - BACKGROUND: Deep infiltrating endometriosis (DIE) is commonly associated with
      severe pain. The pain can be managed successfully with GnRH agonists or
      continuous progestins. The precise molecular mechanism by which DIE causes pain
      or why hormonal treatment is effective, however, remains unclear. We recently
      identified three potential candidate genes that might be involved in DIE pain
      pathways: tyrosine kinase receptor B (TrKB), mu-opioid receptor (MOR) and
      serotonin transporter (5HTT). We hypothesized that if these three genes were
      involved in DIE-associated pain, their expression levels would probably be
      modulated by GnRH agonist or progestin. In this study, we compared mRNA
      expression levels of TrKB, MOR and 5HTT in DIE among patients pre-operatively
      treated with GnRH agonist, progestin or without pre-operative medical treatments.
      METHODS: The expression levels of TrKB, MOR and 5HTT mRNA in DIE were determined
      using laser capture microdissection and real-time RT-PCR techniques. RESULTS: The
      expression levels of TrKB in epithelial cells and MOR in stromal cells from DIE
      were significantly decreased in patients with pre-operative GnRH agonist or
      progestin. There was no significant difference in 5HTT expression levels among
      untreated, GnRH agonist- and progestin-treated patients. CONCLUSION: The
      expression levels of TrKB and MOR genes in DIE appeared to be modulated by GnRH
      agonist or progestin. However, the functional roles of TrKB and MOR in DIE remain
      to be clarified.

PMID- 17000648
TI  - Time to pregnancy and multiple births.
AB  - BACKGROUND: Mothers of multiples are alleged to be more fecund than mothers of
      singletons. Some authors have suggested monitoring twinning rates for assessing
      temporal changes in a population's reproductive health. METHODS: Using a nested
      case-control design, we estimated the odds of a multiple birth in relation to
      fecundity in the US Collaborative Perinatal Project inclusive of 8546 pregnant
      women who reported a known time-to-pregnancy (TTP) upon enrolment in the cohort,
      1959-1966. Case mothers comprised 81 women giving birth to twins/triplets;
      control mothers comprised 243 women giving birth to singletons matched to case
      mothers on maternal age at a ratio of 3:1. The odds ratio (OR) for a multiple
      birth within 6 months of trying adjusting for maternal age and prior pregnancies
      was estimated using logistic regression. Discrete time Cox regression analysis
      was also utilized to estimate the fecundability OR. RESULTS: Women with a TTP of
      <or=6 months were more likely to have a multiple birth than women reporting a TTP
      of >6 months [OR=1.95; 95% confidence interval (95% CI)=1.09-3.51]. Excluding
      pregnancies after 13+ months resulted in a loss of precision (OR=2.14; 95%
      CI=0.90-5.04). CONCLUSIONS: These data support higher fecundity among mothers of
      multiples than mothers of singletons.

PMID- 17000649
TI  - Cryptozoospermia with normal testicular function after allogeneic stem cell
      transplantation: a case report.
AB  - One of the most frequent consequences of allogeneic haemopoietic stem cell
      transplantation (allo-SCT) in both males and females is gonadal insufficiency. We
      report the case of a 27-year-old myelodysplastic male who developed azoospermia
      after allogeneic transplantation of haemopoietic stem cells from his HLA
      identical sister. Post-transplant azoospermia was alternated with intermittent
      severe oligospermia. The patient had a normal endocrine pattern and evidence of
      mild chronic graft-versus-host disease (cGVHD). Normal intratesticular
      spermatogenesis was revealed by bilateral fine needle aspiration (FNA) cytology.
      Inflammation was evident at semen analysis, but no infection was detected by
      microbiological examination and sperm culture. These findings, together with the
      re-appearance of sperm cells at semen analysis after a low-dose immunosuppressive
      treatment, suggested the presence of cGVHD of the urogenital tract, causing a
      reversible obstruction of the spermatic tract and cryptozoospermia. This is the
      first case report documenting a severe impairment of sperm count because of a
      reversible obstruction of the seminal tract, likely caused by cGVHD, in a long
      term survivor of allo-SCT with normal endocrine pattern. An important practical
      consequence of this case report is the fact that azoospermia was cured using low
      dose immunosuppressive therapy, and this allowed us to avoid expensive
      stimulatory treatments with gonadotrophins, which remain, however, ineffective if
      the obstruction of spermatic tracts is not removed. A spontaneous uncomplicated
      pregnancy occurred in the partner of the patient 3 months after the
      corticosteroid treatment withdrawal.

PMID- 17000650
TI  - Parental desire and acceptability of spermatogonial stem cell cryopreservation in
      boys with cancer.
AB  - BACKGROUND: In the near future, a substantial proportion of adults will be
      childhood cancer survivors. The cryopreservation and transplantation of
      spermatogonial stem cells (SSCs) is currently successful in animals; application
      in humans seems likely in the near future. Cryopreserving SSCs might become an
      important issue in childhood cancer. Because this might require testicular
      biopsies or hemicastration, parental desire/acceptability for SSC collection was
      enquired for. METHODS: Three hundred eighteen parents of boys surviving at least
      2 years after the diagnosis of cancer were asked about collecting SSCs by biopsy
      or hemicastration and collecting sperm by masturbation or electrostimulation.
      Opinions were assessed as if at the time of diagnosis and at the present time.
      RESULTS: Sixty-three per cent of parents responded. At diagnosis, SSC collection
      by means of biopsy was approved by 61%, hemicastration by 33% and collecting
      sperm by 70% (P < 0.013). The acceptability of performing hemicastration was
      significantly lower than all other forms of SSC/sperm collection. No differences
      were observed between parents' present opinion and opinion at diagnosis. No
      differences related to treatment intensity, presumed negative fertility effects
      and pubertal state were found. CONCLUSIONS: Infertility is a major topic for
      parents. For prepubertal boys, the collection of SSCs might be a great relief in
      respect of the fertility issue. Collecting SSCs by biopsy is desired and accepted
      by the majority of parents; hemicastration is accepted by one-third of parents.
      The translation of SSC cryopreservation and transplantation from animal models to
      humans is eagerly awaited.

PMID- 17000651
TI  - Cryopreservation of intact human ovary with its vascular pedicle.
AB  - BACKGROUND: The aim of this study was to assess the immediate post-thawing injury
      to the human ovary that was cryopreserved either as a whole with its vascular
      pedicle or as ovarian cortical strips. MATERIALS AND METHODS: Bilateral
      oophorectomy was performed in two women (46 and 44 years old) undergoing vaginal
      hysterectomy and laparoscopic hysterectomy, respectively. Both women agreed to
      donate their ovaries for experimental research. In both patients, one of the
      harvested ovaries was sectioned and cryopreserved (by slow freezing) as ovarian
      cortical strips of 1.0 x 1.0 x 5.0 mm(3) each. The other ovary was cryopreserved
      intact with its vascular pedicle. After thawing 7 days later, follicular
      viability, histology, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      digoxigenin nick-end labelling (TUNEL) assay (to detect apoptosis) and
      immunoperoxidase staining (to define Bcl-2 and p53 protein expression profiles)
      of the ovarian tissue were performed. Tissues from non-cryopreserved ovaries
      served as control specimens (two cases). RESULTS: The overall viability of the
      primordial follicles was 75 and 78% in intact cryopreserved-thawed (C-T) ovaries
      and 81 and 83% in ovarian cortical strips in the 46- and 44-year-old patients,
      respectively. Comparable primordial follicle counts, absence of features of
      necrosis, mean values of apoptosis and weak Bcl-2 and p53 protein expressions
      were observed both in the intact C-T ovary and in the C-T ovarian cortical
      strips. CONCLUSIONS: Cryoperfusion and cryopreservation of entire human ovary can
      be achieved with the maintenance of excellent viability of the superficial and
      the deeper tissues using a slow-freezing protocol. Cryopreservation injury is
      associated neither with significant alteration in the expression pattern of Bcl-2
      and p53 proteins in the ovarian tissues nor with significant follicular damage.

PMID- 17000652
TI  - Estrogenic regulation of host immunity against an estrogen receptor-negative
      human breast cancer.
AB  - PURPOSE: The risk of developing breast cancer is positively correlated with
      exposure to increased levels of estrogen and/or an increased duration of estrogen
      exposure. Many different mechanisms have been proposed to explain the association
      of estrogens with breast cancer risk; however, the well-documented immune
      modulatory properties of estrogen have received little attention. In part, this
      is due to a lack of suitable models for studying this relationship. EXPERIMENTAL
      DESIGN: We have developed an animal model using estrogen receptor (ER)-negative
      human breast cancer cell line, MDA-MB-468, xenografted into severe combined
      immunodeficient (SCID) mice. We also generated the ER-alpha knockout (ER-alphaKO)
      mice on the SCID background and then tested the ability of 17beta-estradiol to
      stimulate growth of xenografted ER-negative human breast cancer tumors in wild
      type and ER-alphaKO SCID mice. We quantified vascularization of tumors,
      macrophage recruitment to the tumor site by immunocytochemistry, and inflammatory
      cytokine production. RESULTS: We show that estrogen treatment of C57BL/6/SCID
      mice promotes the growth of xenografted ER-negative tumors in wild-type mice and
      this estrogen-induced tumor growth is abrogated in ER-alphaKO mice. Tumor
      neovascularization of estrogen-treated mice was unchanged versus control;
      however, estrogen treatment of the C57BL/6/SCID host suppressed macrophage
      recruitment to and inflammatory cytokine production at the tumor site.
      CONCLUSIONS: These data are consistent with estrogen modulation of the
      inflammatory response as a contributing factor in estrogen-stimulated growth of
      an ER-negative tumor. This effect on the host innate immune response was mediated
      by ER-alpha.

PMID- 17000654
TI  - The impact of genetics on sarcoma diagnosis: an evolving science.

PMID- 17000655
TI  - Challenges of chemosensitivity testing.

PMID- 17000656
TI  - Tumor hypoxia imaging.

PMID- 17000657
TI  - Studying human regulatory T cells in vivo.

PMID- 17000658
TI  - The epidermal growth factor receptor pathway: a model for targeted therapy.
AB  - The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase
      receptor that is frequently expressed in epithelial tumors. The EGFR was the
      first receptor to be proposed as a target for cancer therapy, and after 2 decades
      of intensive research, there are several anti-EGFR agents available in the
      clinic. Recent advances in our understanding in the mechanisms of receptor
      activation and function, discovery of primary and secondary EGFR somatic
      mutations, as well as a new generation of anti-EGFR agents provide new leads on
      the clinical targeting of this receptor and may serve as a model for strategies
      aimed at targeting other receptors.

PMID- 17000659
TI  - A new generation of mouse models of cancer for translational research.

PMID- 17000660
TI  - The use of targeted mouse models for preclinical testing of novel cancer
      therapeutics.
AB  - The use of genetically engineered cancer-prone mice as relevant surrogates for
      patients during the development of pertinent clinical applications is an unproven
      expectation that awaits direct demonstration. Despite the generally disappointing
      findings using tumor xenografts and certain early transgenic cancer models to
      predict therapeutic efficacy in patients, the dramatic progress of mouse models
      in recent years engenders optimism that the newest generation of mouse models
      will provide a higher standard of predictive utility in the process of drug
      development.

PMID- 17000661
TI  - Mouse models of brain tumors and their applications in preclinical trials.
AB  - Primary brain tumors, including gliomas and medulloblastomas, often represent the
      most devastating and difficult-to-treat tumors, and are thought to arise from
      glial cells and/or their precursors or the external granule cell layer,
      respectively. The majority of genetic alterations characteristic of the human
      brain tumors are thought to occur in genes encoding proteins involved in signal
      transduction or cell cycle regulation. Accurate recapitulation of these genetic
      alterations using genetically engineered mouse models allows for in vivo modeling
      of brain tumors with similar histopathology, etiology, and biology. These mouse
      models, in turn, increase our understanding of brain tumor initiation, formation,
      progression, and metastasis, providing an experimental system to discover novel
      therapeutic targets and test various therapeutic agents.

PMID- 17000662
TI  - A mouse model system to genetically dissect the molecular mechanisms regulating
      tumorigenesis.
AB  - The vast majority of human tumors are of epithelial origin and result from the
      accumulation of mutations that alter the function of pathways that control
      critical cellular processes, including proliferation, checkpoint regulation, and
      apoptosis. Authentically replicating these events in animal models is critical to
      understanding the biology of cancer and for testing the feasibility of novel
      therapies. We developed a mouse model that recapitulates the steps of epithelial
      tumor progression of multiple tissue types (kidney, breast, ovarian surface, and
      prostate epithelia), which takes advantage of the power of mouse genetics, and
      that allows for biochemical analysis, genetic selection, and screening. Moreover,
      this model enables functional interrogation of far more complex tumor genotypes,
      both of the tumor cells themselves, and of the cells in the tumor
      microenvironment. This is a crucial advantage, as human tumors result from
      multiple compound mutations, most of which are difficult to achieve through
      standard mutant mouse technology. We have applied this model to establish the
      role of apoptosis in epithelial solid tumor progression and in treatment
      response, which has provided novel opportunities for cancer therapies in humans.

PMID- 17000663
TI  - Mouse modeling in oncologic preclinical and translational research.
AB  - Through scientific and technological advancements, our ability to manipulate the
      mouse genome has allowed us to evaluate the effect of specific genetic
      alterations on in vivo tumorigenesis. This has allowed and will allow us to
      define molecular pathways describing the processes of tumor initiation, invasion,
      and progression to metastatic disease. Additionally, these models may serve as an
      excellent platform for the identification of novel molecular targets for therapy
      as well as to evaluate the efficacy of targeted therapies. Ultimately this will
      translate from preclinical mouse model trials to the development of clinical
      trials and protocols for cancer patients. Here we review the usefulness of mouse
      modeling in oncologic translational research.

PMID- 17000664
TI  - Using genetically engineered mouse models of cancer to aid drug development: an
      industry perspective.
AB  - Recent developments in the generation and characterization of genetically
      engineered mouse models of human cancer have resulted in notable improvements in
      these models as platforms for preclinical target validation and experimental
      therapeutics. In this review, we enumerate the criteria used to assess the
      accuracy of various models with respect to human disease and provide some
      examples of their prognostic and therapeutic utility, focusing on models for
      cancers that affect the largest populations. Technological advancements that
      allow greater exploitation of genetically engineered mouse models, such as RNA
      interference in vivo, are described in the context of target and drug validation.
      Finally, this review discusses stratagems for, and obstacles to, the application
      of these models in the drug development process.

PMID- 17000665
TI  - Approval summary: nelarabine for the treatment of T-cell lymphoblastic
      leukemia/lymphoma.
AB  - PURPOSE: To describe the clinical studies, chemistry manufacturing and controls,
      and clinical pharmacology and toxicology that led to Food and Drug Administration
      approval of nelarabine (Arranon) for the treatment of T-cell acute lymphoblastic
      leukemia/lymphoblastic lymphoma. EXPERIMENTAL DESIGN: Two phase 2 trials, one
      conducted in pediatric patients and the other in adult patients, were reviewed.
      The i.v. dose and schedule of nelarabine in the pediatric and adult studies was
      650 mg/m2/d daily for 5 days and 1,500 mg/m2 on days 1, 3, and 5, respectively.
      Treatments were repeated every 21 days. Study end points were the rates of
      complete response (CR) and CR with incomplete hematologic or bone marrow recovery
      (CR*). RESULTS: The pediatric efficacy population consisted of 39 patients who
      had relapsed or had been refractory to two or more induction regimens. CR to
      nelarabine treatment was observed in 5 (13%) patients and CR+CR* was observed in
      9 (23%) patients. The adult efficacy population consisted of 28 patients. CR to
      nelarabine treatment was observed in 5 (18%) patients and CR+CR* was observed in
      6 (21%) patients. Neurologic toxicity was dose limiting for both pediatric and
      adult patients. Other severe toxicities included laboratory abnormalities in
      pediatric patients and gastrointestinal and pulmonary toxicities in adults.
      CONCLUSIONS: On October 28, 2005, the Food and Drug Administration granted
      accelerated approval for nelarabine for treatment of patients with relapsed or
      refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma after at
      least two prior regimens. This use is based on the induction of CRs. The
      applicant will conduct postmarketing clinical trials to show clinical benefit
      (e.g., survival prolongation).

PMID- 17000666
TI  - Protein kinase C as a therapeutic target.

PMID- 17000667
TI  - Curcumin inhibits neurotensin-mediated interleukin-8 production and migration of
      HCT116 human colon cancer cells.
AB  - PURPOSE: Neurotensin, a gut tridecapeptide, acts as a potent cellular mitogen for
      various colorectal and pancreatic cancers that possess high-affinity neurotensin
      receptors. Cytokine/chemokine proteins are increasingly recognized as important
      local factors that play a role in the metastasis and invasion of multiple
      cancers. The purpose of this study was to (a) determine the effect of neurotensin
      on cytokine/chemokine gene expression and cell migration in human cancer cells
      and (b) assess the effect of curcumin, a natural dietary product, on neurotensin
      mediated processes. EXPERIMENTAL DESIGN: The human colorectal cancer, HCT116, was
      treated with neurotensin, with or without curcumin, and interleukin (IL)-8
      expression and protein secretion was measured. Signaling pathways, which
      contribute to the effects of neurotensin, were assessed. Finally, the effect of
      curcumin on neurotensin-mediated HCT116 cell migration was analyzed. RESULTS: We
      show that neurotensin, acting through the native high-affinity neurotensin
      receptor, induced IL-8 expression in human colorectal cancer cells in a time- and
      dose-dependent fashion. This stimulation involves Ca2+-dependent protein kinase
      C, extracellular signal-regulated kinase-dependent activator protein-1, and
      extracellular signal-regulated kinase-independent nuclear factor-kappaB pathways.
      Curcumin inhibited neurotensin-mediated activator protein-1 and nuclear factor
      kappaB activation and Ca2+ mobilization. Moreover, curcumin blocked neurotensin
      stimulated IL-8 gene induction and protein secretion and, at a low concentration
      (i.e., 10 micromol/L), blocked neurotensin-stimulated colon cancer cell
      migration. CONCLUSIONS: Neurotensin-mediated induction of tumor cell IL-8
      expression and secretion may contribute to the procarcinogenic effects of
      neurotensin on gastrointestinal cancers. Furthermore, a potential mechanism for
      the chemopreventive and chemotherapeutic effects of curcumin on colon cancers may
      be through the inhibition of gastrointestinal hormone (e.g., neurotensin)-induced
      chemokine expression and cell migration.

PMID- 17000668
TI  - EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with
      gastrointestinal location and absence of melanocytic differentiation.
AB  - PURPOSE: Clear cell sarcoma (CCS) usually arises in the lower extremities of
      young adults and is typically associated with a t(12;22) translocation resulting
      in the fusion of EWS (EWSR1) with ATF1, a gene encoding a member of the cyclic
      AMP-responsive element binding protein (CREB) family of transcription factors.
      CCS arising in the gastrointestinal tract is rare and its pathologic and
      molecular features are not well defined. EXPERIMENTAL DESIGN: We report a novel
      variant fusion of EWS to CREB1, a gene at 2q32 encoding another CREB family
      member highly related to ATF1, detected in three women with gastrointestinal CCS.
      All three cases contained an identical EWS-CREB1 fusion transcript that was shown
      by reverse transcription-PCR. In two of the cases tested, EWS gene rearrangement
      was also confirmed by fluorescence in situ hybridization and the EWS-CREB1
      genomic junction fragments were isolated by long-range DNA PCR. RESULTS:
      Morphologically, all three tumors lacked melanin pigmentation. By
      immunohistochemistry, there was a strong and diffuse S100 protein reactivity,
      whereas all melanocytic markers were negative. Ultrastructurally, two of the
      cases lacked melanosomes. The melanocyte-specific transcript of MITF was absent
      in two cases, and only weakly expressed in the third case. The Affymetrix gene
      expression data available in one case showed lower expression of the melanocytic
      genes MITF, TYR, and TYRP1, compared with four EWS-ATF1-positive CCSs of non
      gastrointestinal origin. CONCLUSIONS: EWS-CREB1 may define a novel subset of CCS
      that occurs preferentially in the gastrointestinal tract and shows little or no
      melanocytic differentiation. Thus, evidence of melanocytic lineage or
      differentiation is not a necessary feature of sarcomas with gene fusions
      involving CREB family members.

PMID- 17000669
TI  - Overexpression of cyclase-associated protein 2 in multistage
      hepatocarcinogenesis.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) associated with chronic liver disease is
      known to show an obvious multistage process of tumor progression. We previously
      identified heat shock protein 70 as a molecular marker of early HCC during
      investigation of expression profiling in multistage hepatocarcinogenesis. In this
      report, we examined cyclase-associated protein 2 (CAP2), which is also listed as
      an up-regulated gene in early HCC. EXPERIMENTAL DESIGN: We measured the level of
      CAP2 mRNA by real-time quantitative PCR. We raised a polyclonal antibody against
      CAP2 and we confirmed the expression of CAP2 by immunoblotting and
      immunohistochemistry in HCC cell lines and HCC tissues. RESULTS: According to
      real-time quantitative PCR, the level of CAP2 mRNA was up-regulated in early HCC
      when compared with noncancerous liver tissue, and it was further up-regulated in
      progressed HCC. We raised a polyclonal antibody against CAP2, which showed a
      single 53-kDa band of strong intensity in the human HCC cell lines and HCC
      tissues but only a weak band in the noncancerous liver tissues in Western blot
      analysis. Immunohistochemical examination of CAP2 revealed its significant
      overexpression in early HCC when compared with noncancerous and precancerous
      lesions and in progressed HCC when compared with early HCC. CONCLUSION: Our
      findings show that CAP2 is up-regulated in HCC when compared with noncancerous
      and precancerous lesions. This is the first report that proves that CAP2 is up
      regulated in human cancers and that this is possibly related to multistage
      hepatocarcinogenesis.

PMID- 17000670
TI  - Twist overexpression correlates with hepatocellular carcinoma metastasis through
      induction of epithelial-mesenchymal transition.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is a rapidly growing tumor associated
      with a high propensity for vascular invasion and metastasis. Epithelial
      mesenchymal transition (EMT) is a key event in the tumor invasion process.
      Recently, Twist has been identified to play an important role in EMT-mediated
      metastasis through the regulation of E-cadherin expression. However, the actual
      role of Twist in tumor invasiveness remains unclear. The purpose of this study is
      to investigate the expression and possible role of Twist in HCC. EXPERIMENTAL
      DESIGN: We evaluated Twist and E-cadherin expression in HCC tissue microarray of
      paired primary and metastatic HCC by immunohistochemical staining. The role of
      Twist in EMT-mediated invasiveness was also evaluated in vitro in HCC cell lines.
      RESULTS: We first showed that overexpression of Twist was correlated with HCC
      metastasis (P=0.001) and its expression was negatively correlated with E-cadherin
      expression (P=0.001, r=-0.443) by tissue microarray. A significant increase of
      Twist at the mRNA level was also found in metastatic HCC cell lines MHCC-97H,
      MHCC-97L, and H2M when compared with nonmetastatic Huh-7, H2P, and PLC cell
      lines. The MHCC-97H cell line, which has a higher metastatic ability, was found
      to have a higher level of Twist than MHCC-97L. Accompanied with increased Twist
      expression in the metastatic HCC cell lines when compared with the nonmetastatic
      primary ones, we found decreased E-cadherin mRNA expression in the metastatic HCC
      cell lines. By ectopic transfection of Twist into PLC cells, Twist was able to
      suppress E-cadherin expression and induce EMT changes, which was correlated with
      increased HCC cell invasiveness. CONCLUSION: This study shows that Twist
      overexpression was correlated with HCC metastasis through induction of EMT
      changes and HCC cell invasiveness.

PMID- 17000671
TI  - Novel thioredoxin inhibitors paradoxically increase hypoxia-inducible factor
      alpha expression but decrease functional transcriptional activity, DNA binding,
      and degradation.
AB  - PURPOSE: Hypoxia-inducible factor-alpha (HIF-alpha) is a transcription factor
      that regulates the response to hypoxia. HIF-alpha protein is found at high levels
      in many cancers, and the redox protein thioredoxin-1 (Trx-1) increases both
      aerobic and hypoxia-induced HIF-alpha. Therefore, Trx-1 and HIF-alpha are
      attractive molecular targets for novel cancer therapeutics. EXPERIMENTAL DESIGN:
      We investigated whether two novel anticancer drugs AJM290 and AW464 (quinols),
      which inhibit Trx-1 function, can inhibit the HIF pathway. RESULTS: Treatment of
      several cancer cell lines with AJM290 or AW464 prevented the hypoxia-induced
      increase of vascular endothelial growth factor (VEGF) at subtoxic concentrations.
      AJM290 and AW464 also decreased VEGF in pVHL mutant renal cell carcinoma cells
      that constitutively overexpress HIF-alpha protein. They surprisingly up-regulated
      HIF-alpha expression in breast cancer cell lines in normoxia and hypoxia as well
      as in pVHL mutant cells. In the MDA-MB-468 breast cancer cell line, the compounds
      inhibited RNA and protein expression of the HIF-alpha target genes, carbonic
      anhydrase IX, VEGF, and BNIP3, concordantly with HIF-alpha up-regulation. Both
      compounds specifically inhibited HIF-alpha-dependent induction of hypoxia
      regulatory element-luciferase and HIF-1alpha hypoxia regulatory element-DNA
      binding. To analyze the HIF-1alpha domain inhibited by AJM290, we transfected
      cells with plasmids expressing a fusion protein of Gal linked to HIF-1alpha or
      HIF-1alpha COOH-terminal transactivation domain (CAD) with a Gal4-responsive
      luciferase reporter gene. AJM290 inhibited both the full-length HIF-1alpha and
      HIF-1alpha CAD transcriptional activity. CONCLUSIONS: AJM290 and AW464 are
      inhibitors of HIF-1alpha CAD transcription activity and DNA binding, but they
      also inhibit degradation of HIF, in contrast to other Trx inhibitors.

PMID- 17000672
TI  - Snail and slug play distinct roles during breast carcinoma progression.
AB  - PURPOSE: Carcinoma progression is linked to a partially dedifferentiated
      epithelial cell phenotype. As previously suggested, this regulation could involve
      transcription factors, Snail and Slug, known to promote epithelial-mesenchymal
      transitions during development. Here, we investigate the role of Snail and Slug
      in human breast cancer progression. EXPERIMENTAL DESIGN: We analyzed Snail, Slug,
      and E-cadherin RNA expression levels and protein localization in large numbers of
      transformed cell lines and breast carcinomas, examined the correlation with tumor
      histologic features, and described, at the cellular level, Snail and Slug
      localization in carcinomas using combined in situ hybridization and
      immunolocalization. RESULTS: In contrast with transformed cell lines, Slug was
      found to colocalize with E-cadherin at the cellular level in normal mammary
      epithelial cells and all tested carcinomas. Snail also colocalized at the
      cellular level with E-cadherin in tumors expressing high levels of Snail RNA. In
      addition, Snail was significantly expressed in tumor stroma, varying with tumors.
      Slug and Snail genes were significantly overexpressed in tumors associated with
      lymph node metastasis. Finally, the presence of semidifferentiated tubules within
      ductal carcinomas was linked to Slug expression levels similar to or above normal
      breast samples. CONCLUSIONS: These results suggest that Snail or Slug expression
      in carcinoma cells does not generally preclude significant E-cadherin expression.
      They emphasize a link between Snail, Slug, and lymph node metastasis in a large
      sampling of mammary carcinomas, and suggest a role for Slug in the maintenance of
      semidifferentiated structures. Snail and Slug proteins seem to support distinct
      tumor invasion modes and could provide new therapeutic targets.

PMID- 17000673
TI  - HATH1 expression in mucinous cancers of the colorectum and related lesions.
AB  - PURPOSE: Mucinous cancers and signet ring carcinomas are distinct classes of
      colon cancers characterized by their production of copious quantities of
      intestinal goblet cell mucin, MUC2. Deletion of transcription factor HATH1
      ablates the biogenesis of goblet cells in developing mouse intestine, and forced
      expression of HATH1 results in elevated expression of MUC2 in colon cancer cells.
      The aim of this study was to assess the possible role of HATH1 in the development
      of mucinous cancers and signet ring carcinomas. EXPERIMENTAL DESIGN:
      Immunohistochemistry and confocal microscopy was used to examine HATH1 expression
      and subcellular distribution in normal colon and small intestine, mucinous
      cancers, signet ring carcinomas, and nonmucinous cancers and in precursor
      lesions, including hyperplastic polyps, serrated adenomas, tubular adenomas, and
      villous adenomas. We also analyzed the transactivation of MUC2 promoter/reporter
      constructs by a HATH1 expression vector. RESULTS: HATH1 expression transactivated
      MUC2 promoter/reporter constructs, an activity that was significantly inhibited
      by mutation of putative HATH1-binding sites. HATH1 was expressed in the nuclei of
      goblet cells and in the cytoplasm and nuclei of enteroendocrine cells of the
      colon. In the small intestine, only cytoplasmic expression of HATH1 in
      enteroendocrine cells was detected. HATH1 was found to be strongly expressed in
      the nuclei of hyperplastic polyps, serrated adenomas, villous adenomas, mucinous
      cancers, and signet ring carcinomas but repressed in nonmucinous cancers and
      tubular adenomas. CONCLUSIONS: This study confirms the importance of HATH1 for
      the development of intestinal secretory cells. The results further suggest that
      HATH1 is an important factor in the up-regulation of MUC2 expression that occurs
      in mucinous cancers and signet ring carcinomas. In addition, the expression of
      HATH1 in hyperplastic polyps, serrated adenomas, and villous adenomas lends
      support to the hypothesis that these neoplasms are frequent precursors in
      mucinous cancer and signet ring carcinoma development.

PMID- 17000674
TI  - S100P is an early developmental marker of pancreatic carcinogenesis.
AB  - PURPOSE: Our goal was to clarify the involvement and clinical significance of
      S100P in pancreatic carcinogenesis. EXPERIMENTAL DESIGN: We examined S100P
      expression in 45 bulk pancreatic tissues; in microdissected cells, including
      invasive ductal carcinoma (IDC) cells (20 sections), pancreatic intraepithelial
      neoplasia (PanIN) cells (12 sections), intraductal papillary mucinous neoplasm
      (IPMN) cells (19 sections), and normal epithelial cells (11 sections); and in
      pancreatic juice samples from 99 patients with pancreatic diseases (32 cancer, 35
      IPMN, and 32 chronic pancreatitis samples). We used quantitative real-time
      reverse transcription-PCR with gene-specific priming to measure S100P in these
      various types of samples. RESULTS: In bulk tissue analyses, pancreatic cancer and
      IPMN expressed significantly higher levels of S100P than did nonneoplastic
      pancreas (P<0.017 and P=0.0013, respectively). Microdissection analyses revealed
      that IPMN expressed significantly higher levels of S100P than did IDC (P<0.0001)
      and PanIN (P=0.0031), although S100P expression did not differ between IDC and
      PanIN (P=0.077). In pancreatic juice analyses, cancer and IPMN juice expressed
      significantly higher levels of S100P than did pancreatitis juice (both P<0.0001).
      Receiver operating characteristic curve analyses revealed that measurement of
      S100P in pancreatic juice was useful for discriminating neoplastic disease from
      chronic pancreatitis (area under the curve=0.837; 95% confidence interval, 0.749
      0.903). CONCLUSION: S100P may be an early developmental marker of pancreatic
      carcinogenesis, and measurement of S100P in pancreatic juice may be useful for
      early detection of pancreatic cancer or screening of early pancreatic
      carcinogenesis.

PMID- 17000675
TI  - S100A11, a putative tumor suppressor gene, is overexpressed in pancreatic
      carcinogenesis.
AB  - PURPOSE: Recent microarray analyses revealed that expression of S100A11 is up
      regulated in pancreatic cancer. The aim of the present study was to evaluate the
      association of S100A11 with pancreatic carcinogenesis. EXPERIMENTAL DESIGN: We
      measured S100A11 mRNA expression in various clinical samples related to
      pancreatic cancer and its precursor lesions, intraductal papillary mucinous
      neoplasm (IPMN) and pancreatic intraepithelial neoplasia, by quantitative reverse
      transcription-PCR. RESULTS: Levels of S100A11 were significantly higher in
      pancreatic cancer (n=22) and IPMN (n=18) bulk tissues than in nonneoplastic bulk
      tissues (n=22; P<0.0001 for both). Levels of S100A11 did not differ between
      pancreatic cancer and IPMN bulk tissues. In microdissection analyses, however,
      IPMN cells (n=21) expressed significantly higher levels of S100A11 than did
      cancer cells (n=23; P=0.003). The median level of S100A11 expression was higher
      in pancreatic intraepithelial neoplasia cells (n=6) than in cancer cells. In
      pancreatic juice analyses, cancer-related (n=24; P=0.004) and IPMN-related (n=18;
      P=0.001) juice expressed significantly higher levels of S100A11 than did chronic
      pancreatitis-related juice (n=23). CONCLUSIONS: The present data suggest that
      expression of S100A11, a putative tumor suppressor gene, is increased in the
      early stage of pancreatic carcinogenesis and decreased during subsequent
      progression to cancer. Analysis of the S100A11 level in pancreatic juice may be
      an effective tool for screening of patients with high-risk lesions that could
      progress to pancreatic cancer or detecting early-stage pancreatic cancer.

PMID- 17000676
TI  - Prevalence of FOXP3+ regulatory T cells increases during the progression of
      pancreatic ductal adenocarcinoma and its premalignant lesions.
AB  - PURPOSE: Antitumor immune response changes drastically during the progression of
      cancers. Established cancers often escape from the host immune system, although
      specific immune surveillance operates in the early stages of tumorigenesis in
      murine models. CD4+CD25+ regulatory T cells (TR) play a central role in self
      tolerance and suppress effective antitumor immune responses. The aim of this
      study was to investigate the clinical significance and roles of TR in the
      progression and multistep carcinogenesis of pancreatic ductal adenocarcinoma.
      EXPERIMENTAL DESIGN: We raised anti-FOXP3 antibodies and used them in
      immunohistochemical studies of the prevalence of FOXP3+CD4+CD25+ TR in the CD4+ T
      cells, which infiltrated in tissue and draining lymph nodes of 198 pancreatic
      ductal adenocarcinomas, their premalignant lesions (84 lesions of pancreatic
      intraepithelial neoplasias and 51 intraductal papillary-mucinous neoplasms), and
      15 nonneoplastic pancreatic lesions. RESULTS: The prevalence of TR was
      significantly increased in the ductal adenocarcinomas compared with that in the
      stroma of nonneoplastic inflammation (P<0.0001). The increased prevalence of T(R)
      was significantly correlated with certain clinicopathologic factors. A better
      prognosis was observed in patients with a low prevalence of T(R), and this was
      independent of other survival factors (P<0.0001). Infiltration of intraepithelial
      CD8+TIA-1+ cytotoxic T cells in pancreatic ducts was marked in low-grade
      premalignant lesions but diminished during the progression of both pancreatic
      intraepithelial neoplasias and intraductal papillary-mucinous neoplasms.
      Conversely, the prevalence of TR increased significantly during the progression
      of premalignant lesions. CONCLUSIONS: T(R) play a role in controlling the immune
      response against pancreatic ductal carcinoma from the premalignant stage to
      established cancer. In pancreatic ductal carcinoma, a high prevalence of TR seems
      to be a marker of poor prognosis.

PMID- 17000677
TI  - Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography
      in head and neck cancer.
AB  - PURPOSE: Advanced head and neck cancer shows hypoxia that results in biological
      changes to make the tumor cells more aggressive and less responsive to treatment
      resulting in poor survival. [F-18] fluoromisonidazole (FMISO) positron emission
      tomography (PET) has the ability to noninvasively quantify regional hypoxia. We
      investigated the prognostic effect of pretherapy FMISO-PET on survival in head
      and neck cancer. EXPERIMENTAL DESIGN: Seventy-three patients with head and neck
      cancer had pretherapy FMISO-PET and 53 also had fluorodeoxyglucose (FDG) PET
      under a research protocol from April 1994 to April 2004. RESULTS: Significant
      hypoxia was identified in 58 patients (79%). The mean FMISO tumor/bloodmax
      (T/Bmax) was 1.6 and the mean hypoxic volume (HV) was 40.2 mL. There were 28
      deaths in the follow-up period. Mean FDG standard uptake value (SUV)max was 10.8.
      The median time for follow-up was 72 weeks. In a univariate analysis, T/Bmax
      (P=0.002), HV (P=0.04), and the presence of nodes (P=0.01) were strong
      independent predictors. In a multivariate analysis, including FDG SUVmax, no
      variable was predictive at P<0.05. When FDG SUVmax was removed from the model
      (resulting in n=73 with 28 events), nodal status and T/Bmax (or HV) were both
      highly predictive (P=0.02, 0.006 for node and T/Bmax, respectively; P=0.02 and
      0.001 for node and HV, respectively). CONCLUSIONS: Pretherapy FMISO uptake shows
      a strong trend to be an independent prognostic measure in head and neck cancer.

PMID- 17000678
TI  - Cancer-testis antigens: expression and correlation with survival in human
      urothelial carcinoma.
AB  - PURPOSE: Vaccination against human cancer is a promising therapeutic approach but
      the optimal antigen or antigens remain undefined. Cancer-testis antigens (CTA), a
      family of tumor-associated antigens, have both potent immunogenicity and
      restricted expression patterns in normal adult tissues, highly desirable
      characteristics for targets of anticancer vaccines. These antigens were evaluated
      for both the degree of expression and prognostic value in cancer of the
      urothelium. EXPERIMENTAL DESIGN: The expression patterns of nine CTAs (NY-ESO-1,
      LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7, CT10, and GAGE) were examined
      by immunohistochemistry and reverse transcription-PCR in a panel of high-grade
      urothelial carcinomas of the urinary bladder. Also assessed were correlations
      between the expression of CTAs by immunohistochemistry and both disease-free and
      overall survival. RESULTS: At least one CTA was expressed in 77% of samples and
      61% of these tumors expressed more than one CTA. Additionally, patients with CT10
      positive tumors had an improved disease-free survival (P=0.008) and overall
      survival (P=0.037) compared with patients with CT10-negative tumors. CONCLUSIONS:
      These findings establish CTAs as potential prognostic markers and as target
      candidates for vaccine development for patients with urothelial carcinoma.

PMID- 17000679
TI  - Matrix metalloproteinase polymorphisms and survival in stage I non-small cell
      lung cancer.
AB  - PURPOSE: The matrix metalloproteinases (MMP) are a family of enzymes that can
      degrade extracellular matrix and facilitate invasion through the basement
      membrane. Several polymorphisms in MMP-1, MMP-2, MMP-3, and MMP-12 have been
      described, some of which lead to differential transcription. We hypothesized that
      polymorphisms in these MMP genes may be associated with survival outcomes in
      early-stage non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We evaluated
      the relationship between MMP-1, MMP-2, MMP-3, and MMP-12 polymorphisms and both
      recurrence-free survival (RFS) and overall survival (OS) among 382 patients with
      stage I NSCLC. Analyses of genotype associations with survival outcomes were done
      using Cox proportional hazards models and Kaplan-Meier methods and the log-rank
      test. RESULTS: Patients carrying the variant G allele of the MMP-12 1082A/G
      polymorphism had significantly worse outcomes [crude hazard ratio (HR) for OS
      1.74; 95% confidence interval (95% CI), 1.18-2.58, P=0.006; crude HR for RFS,
      1.53; 95% CI, 1.05-2.23, P=0.03]. After adjusting for age, sex, stage, pack-years
      of smoking, and histologic subtype, the MMP-12 1082A/G polymorphism remained
      significantly associated with survival outcomes [adjusted HR (AHR) for OS, 1.94;
      95% CI, 1.28-2.97, P=0.002; AHR for RFS, 1.61; 95% CI, 1.07-2.41, P=0.02]. None
      of the other MMP polymorphisms was significantly associated with survival.
      CONCLUSIONS: Our results show that patients with stage I NSCLC carrying the
      variant G allele of the MMP-12 1082A/G polymorphism have worse survival.

PMID- 17000680
TI  - In vitro drug sensitivity predicts response and survival after individualized
      sensitivity-directed chemotherapy in metastatic melanoma: a multicenter phase II
      trial of the Dermatologic Cooperative Oncology Group.
AB  - PURPOSE: In vitro sensitivity assays are promising tools to predict the
      individual outcome of different chemotherapy regimens. However, a direct
      association between in vitro and in vivo chemosensitivity has to be shown by
      clinical studies. This multicenter phase II trial was aimed to investigate the
      efficacy of a sensitivity-directed, first-line chemotherapy in metastasized
      melanoma patients, and to prove an association between in vitro sensitivity and
      therapy outcome. PATIENTS AND METHODS: The primary study end point was objective
      response; secondary end points were safety, overall survival, and progression
      free survival. Viable tumor cells obtained from metastatic lesions were tested
      for chemosensitivity to seven single drugs and five drug combinations using an
      ATP-based luminescence viability assay. RESULTS: Out of 82 recruited patients
      (intention-to-treat), 57 received assay-directed chemotherapy and 53 were
      evaluable for all study end points (per protocol). The drug combinations used
      were gemcitabine+treosulfan, paclitaxel+cisplatin, paclitaxel+doxorubicin, and
      gemcitabine+cisplatin. The per protocol population could be divided into 22 (42%)
      chemosensitive and 31 (58%) chemoresistant patients by an arbitrary
      chemosensitivity index. Objective response was 36.4% in chemosensitive patients
      compared with 16.1% in chemoresistant patients (P=0.114); progression arrest
      (complete response+partial response+stable disease) was 59.1% versus 22.6%
      (P=0.01). Chemosensitive patients showed an increased overall survival of 14.6
      months compared with 7.4 months in chemoresistant patients (P=0.041). CONCLUSION:
      In vitro chemosensitivity testing may be worthy of further exploration to see if
      it could be a useful tool to predict the outcome of melanoma patients treated
      with a sensitivity-directed chemotherapy. Therefore, these preliminary results
      will be evaluated by a planned phase III trial using a randomized, standard
      regimen controlled setting.

PMID- 17000681
TI  - Photofrin uptake in the tumor and normal tissues of patients receiving
      intraperitoneal photodynamic therapy.
AB  - PURPOSE: A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown
      in a previous report limited efficacy and significant acute, but not chronic,
      toxicity. A secondary aim of this trial and the subject of this report is to
      determine Photofrin uptake in tumor and normal tissues. EXPERIMENTAL DESIGN:
      Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery.
      Photofrin uptake was measured by spectroflurometric analysis of drug extracted
      from tumor and normal tissues removed at surgery. Differences in drug uptake
      among these tissues were statistically considered using mixed-effects models.
      RESULTS: Photofrin concentration was measured in 301 samples collected from 58 of
      100 patients enrolled on the trial. In normal tissues, drug uptake significantly
      (P<0.0001) differed as a function of seven different tissue types. In the
      toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level
      was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large
      and small intestine, respectively. In tumors, drug uptake significantly
      (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin
      level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel
      cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon
      cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small
      bowel cancers showed significantly higher Photofrin uptake than full-thickness
      large and/or small intestine. However, the ratio of mean drug level in tumor
      versus intestine was modest (<or=2.31). CONCLUSIONS: Some selectivity is found in
      Photofrin uptake between tumor and normal tissues of the peritoneal cavity, but
      absolute differences in drug uptake relative to toxicity-limiting normal tissues
      (intestine) are small. This narrow differential in drug selectivity likely
      contributes to a narrow window in therapeutic application, which has been
      previously reported.

PMID- 17000682
TI  - A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in
      patients with advanced solid tumors.
AB  - PURPOSE: PI-88 is a mixture of highly sulfated oligosaccharides that inhibits
      heparanase, an extracellular matrix endoglycosidase, and the binding of
      angiogenic growth factors to heparan sulfate. This agent showed potent inhibition
      of placental blood vessel angiogenesis as well as growth inhibition in multiple
      xenograft models, thus forming the basis for this study. EXPERIMENTAL DESIGN:
      This study evaluated the toxicity and pharmacokinetics of PI-88 (80-315 mg) when
      administered s.c. daily for 4 consecutive days bimonthly (part 1) or weekly (part
      2). RESULTS: Forty-two patients [median age, 53 years (range, 19-78 years);
      median performance status, 1] with a range of advanced solid tumors received a
      total of 232 courses. The maximum tolerated dose was 250 mg/d. Dose-limiting
      toxicity consisted of thrombocytopenia and pulmonary embolism. Other toxicity was
      generally mild and included prolongation of the activated partial thromboplastin
      time and injection site echymosis. The pharmacokinetics were linear with dose.
      Intrapatient variability was low and interpatient variability was moderate. Both
      AUC and C(max) correlated with the percent increase in activated partial
      thromboplastin time, showing that this pharmacodynamic end point can be used as a
      surrogate for drug exposure. No association between PI-88 administration and
      vascular endothelial growth factor or basic fibroblast growth factor levels was
      observed. One patient with melanoma had a partial response, which was maintained
      for >50 months, and 9 patients had stable disease for >or=6 months. CONCLUSION:
      The recommended dose of PI-88 administered for 4 consecutive days bimonthly or
      weekly is 250 mg/d. PI-88 was generally well tolerated. Evidence of efficacy in
      melanoma supports further evaluation of PI-88 in phase II trials.

PMID- 17000683
TI  - Population pharmacokinetic-pharmacodynamic model for neutropenia with patient
      subgroup identification: comparison across anticancer drugs.
AB  - PURPOSE: Cancer chemotherapy, although based on body surface area, often causes
      unpredictable myelosuppression, especially severe neutropenia. The aim of this
      study was to evaluate qualitatively and quantitatively the influence of patient
      specific characteristics on the neutrophil concentration-time course, to identify
      patient subgroups, and to compare covariates on system-related pharmacodynamic
      variable between drugs. EXPERIMENTAL DESIGN: Drug and neutrophil concentration,
      demographic, and clinical chemistry data of several trials with docetaxel (637
      patients), paclitaxel (45 patients), etoposide (71 patients), or topotecan (191
      patients) were included in the covariate analysis of a physiology-based
      pharmacokinetic-pharmacodynamic neutropenia model. Comparisons of covariate
      relations across drugs were made. RESULTS: A population model incorporating four
      to five relevant patient factors for each drug to explain variability in the
      degree and duration of neutropenia has been developed. Sex, previous anticancer
      therapy, performance status, height, binding partners, or liver enzymes
      influenced system-related variables and alpha1-acid glycoprotein, albumin,
      bilirubin, concomitant cytotoxic agents, or administration route changed drug
      specific variables. Overall, female and pretreated patients had a lower baseline
      neutrophil concentration. Across-drug comparison revealed that several covariates
      (e.g., age) had minor (clinically irrelevant) influences but consistently shifted
      the pharmacodynamic variable in the same direction. CONCLUSIONS: These
      mechanistic models, including patient characteristics that influence drug
      specific parameters, form the rationale basis for more tailored dosing of
      individual patients or subgroups to minimize the risk of infection and thus might
      contribute to a more successful therapy. In addition, nonsignificant or
      clinically irrelevant relations on system-related parameters suggest that these
      covariates could be negligible in clinical trails and daily use.

PMID- 17000684
TI  - Increased prevalence of dihydropyrimidine dehydrogenase deficiency in African
      Americans compared with Caucasians.
AB  - PURPOSE: African-American patients with colorectal cancer were observed to have
      increased 5-fluorouracil (5-FU)-associated toxicity (leukopenia and anemia) and
      decreased overall survival compared with Caucasian patients. One potential source
      for this disparity may be differences in 5-FU metabolism. Dihydropyrimidine
      dehydrogenase (DPD), the initial and rate-limiting enzyme of 5-FU catabolism, has
      previously been shown to have significant interpatient variability in activity.
      Several studies have linked reduced DPD activity to the development of 5-FU
      toxicity. Although the distribution of DPD enzyme activity and the frequency of
      DPD deficiency have been well characterized in the Caucasian population, the
      distribution of DPD enzyme activity and the frequency of DPD deficiency in the
      African-American population are unknown. EXPERIMENTAL DESIGN: Healthy African
      American (n=149) and Caucasian (n=109) volunteers were evaluated for DPD
      deficiency using both the [2-(13)C]uracil breath test and peripheral blood
      mononuclear cell DPD radioassay. RESULTS: African-Americans showed significantly
      reduced peripheral blood mononuclear cell DPD enzyme activity compared with
      Caucasians (0.26+/-0.07 and 0.29+/-0.07 nmol/min/mg, respectively; P=0.002). The
      prevalence of DPD deficiency was 3-fold higher in African-Americans compared with
      Caucasians (8.0% and 2.8%, respectively; P=0.07). African-American women showed
      the highest prevalence of DPD deficiency compared with African-American men,
      Caucasian women, and Caucasian men (12.3%, 4.0%, 3.5%, and 1.9%, respectively).
      CONCLUSION: These results indicate that African-Americans, particularly African
      American women, have significantly reduced DPD enzyme activity compared with
      Caucasians, which may predispose this population to more 5-FU toxicity.

PMID- 17000685
TI  - Pharmacogenetics of capecitabine in advanced breast cancer patients.
AB  - PURPOSE: Germinal gene polymorphisms can explain a part of the interpatient
      pharmacodynamic variability of anticancer drugs, particularly fluoropyrimidines.
      Genes for which polymorphisms may potentially influence pharmacodynamics of
      fluoropyrimidines, including capecitabine, are thymidylate synthase (TS),
      methylenetetrahydrofolate reductase (MTHFR), and dihydropyrimidine dehydrogenase
      (DPD). EXPERIMENTAL DESIGN: The aim of this prospective pilot study was to
      analyze the effect of TS, MTHFR, and DPD gene polymorphisms on toxicity and
      efficacy in advanced breast cancer patients receiving capecitabine as
      monotherapy. Germinal polymorphisms of TS (6 bp deletion in the 3' region and 28
      bp repeats, including G>C mutation in the 5' region), MTHFR (677C>T and 1298A>C),
      and DPD (IVS14+1G>A) were determined in 105 consecutive patients. RESULTS: A
      trend toward a higher global toxicity grade 3 and 4 was observed in patients
      homozygous for the TS 3RG allele compared with patients heterozygous for the 3RG
      allele or patients not carrying the 3RG allele (50% versus 19% versus 13%
      respectively, P=0.064). The sole patient bearing the DPD IVS14+1G>A mutation
      (heterozygous) deceased from hematologic toxicity. The median response duration
      was 5.8 months (95% confidence interval, 4.3-7.2). Duration of response was
      significantly shortened in patients homozygous for the 3RG allele compared with
      others (P=0.037). CONCLUSIONS: The present data suggest that 3RG3RG breast cancer
      patients are not good candidates for capecitabine therapy. In addition, attention
      should be paid to DPD deficiency in breast cancer patients receiving
      capecitabine. These preliminary data require further confirmation on a larger
      number of patients.

PMID- 17000686
TI  - Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube,
      or primary peritoneal cancer.
AB  - PURPOSE: This open-label study assessed the safety and immunogenicity of two
      doses and two routes of the anti-idiotypic monoclonal antibody abagovomab
      (formerly ACA125) in patients with epithelial ovarian, fallopian tube, or primary
      peritoneal cancer. EXPERIMENTAL DESIGN: Eligible patients from the three
      participating institutions were any stage at diagnosis, had relapsed, and had
      complete or partial response to additional chemotherapy. Patients were randomized
      to receive abagovomab at 2.0 versus 0.2 mg and i.m. versus s.c. for four
      immunizations every 2 weeks and then monthly for two additional immunizations.
      Planned evaluation included interval physical examinations and laboratory
      assessments with immune assessment, including HLA typing, human anti-mouse
      antibody, ELISA, and enzyme-linked immunospot. Patients were required to remain
      on study until week 10 (the first post-baseline Ab3 determination) to be
      considered for immunologic assessment. The primary end points were safety and
      immunogenicity primarily determined by Ab3 response. RESULTS: Forty-two patients
      received at least one vaccination and were eligible for safety analysis. Thirty
      three patients were available for Ab3 analysis (removed for progression of
      disease, 6; withdrawal of consent, 2; unrelated adverse event, 1). The most
      common adverse events were self-limited pain at injection site, myalgia, and
      fever. No hematologic or nonhematologic toxicity grade>2 related to immunization
      was seen. Ab3 was detectable in all patients (median, 236,794 ng/mL); none of
      route of administration (P=0.6268), dose (P=0.4602), or cohort (P=0.4944) was
      statistically significant in terms of effect on maximum post-baseline Ab3 titer.
      Human anti-mouse antibody was not detectable at baseline but was present in all
      patients at week 16 (range, 488-45,000 ng/mL). CONCLUSIONS: Immunization with
      abagovomab is well tolerated and induced robust Ab3 responses at the two doses
      and routes tested. A phase III randomized study with abagovomab (2.0 mg s.c.) is
      warranted.

PMID- 17000687
TI  - Adjuvanticity of plasmid DNA encoding cytokines fused to immunoglobulin Fc
      domains.
AB  - PURPOSE: Plasmid DNAs encoding cytokines enhance immune responses to vaccination
      in models of infectious diseases and cancer. We compared DNA adjuvants for their
      ability to enhance immunity against a poorly immunogenic self-antigen expressed
      by cancer. EXPERIMENTAL DESIGN: DNAs encoding cytokines that affect T cells
      [interleukin (IL)-2, IL-12, IL-15, IL-18, IL-21, and the chemokine CCL21] and
      antigen-presenting cells [granulocyte macrophage colony-stimulating factor (GM
      CSF)] were compared in mouse models as adjuvants to enhance CD8+ T-cell responses
      and tumor immunity. A DNA vaccine against a self-antigen, gp100, expressed by
      melanoma was used in combination with DNA encoding cytokines and cytokines fused
      to the Fc domain of mouse IgG1 (Ig). RESULTS: We found that (a) cytokine DNAs
      generally increased CD8+ T-cell responses against gp100; (b) ligation to Fc
      domains further enhanced T-cell responses; (c) adjuvant effects were sensitive to
      timing of DNA injection; (d) the most efficacious individual adjuvants for
      improving tumor-free survival were IL-12/Ig, IL-15/Ig, IL-21/Ig, GM-CSF/Ig, and
      CCL21; and (e) combinations of IL-2/Ig+IL-12/Ig, IL-2/Ig+IL-15/Ig, IL-12/Ig+IL
      15/Ig, and IL-12/Ig+IL-21/Ig were most active; and (f) increased adjuvanticity of
      cytokine/Ig fusion DNAs was not related to higher tissue levels or greater
      stability. CONCLUSIONS: These observations support the potential of cytokine DNA
      adjuvants for immunization against self-antigens expressed by cancer, the
      importance of timing, and the enhancement of immune responses by Fc domains
      through mechanisms unrelated to increased half-life.

PMID- 17000688
TI  - Human regulatory T cells control xenogeneic graft-versus-host disease induced by
      autologous T cells in RAG2-/-gammac-/- immunodeficient mice.
AB  - PURPOSE: Effective prevention of graft-versus-host disease (GvHD) is a major
      challenge to improve the safety of allogeneic stem cell transplantation for
      leukemia treatment. In murine transplantation models, administration of naturally
      occurring CD4+CD25+ regulatory T cells (Treg) can prevent GvHD. Toward
      understanding the role of human Treg in stem cell transplantation, we studied
      their capacity to modulate T-cell-dependent xenogeneic (x)-GvHD in a new model
      where x-GvHD is induced in RAG2-/-gammac-/- mice by i.v. administration of human
      peripheral blood mononuclear cells (PBMC). EXPERIMENTAL DESIGN: Human PBMC,
      depleted of or supplemented with autologous CD25+ Tregs, were administered in
      mice at different doses. The development of x-GvHD, in vivo expansion of human T
      cells, and secretion of human cytokines were monitored at weekly intervals.
      RESULTS: Depletion of CD25+ cells from human PBMC significantly exacerbated x
      GvHD and accelerated its lethality. In contrast, coadministration of Treg
      enriched CD25+ cell fractions with autologous PBMC significantly reduced the
      lethality of x-GvHD. Treg administration significantly inhibited the explosive
      expansion of effector CD4+ and CD8+ T cells. Interestingly, protection from x
      GvHD after Treg administration was associated with a significant increase in
      plasma levels of interleukin-10 and IFN-gamma, suggesting the de novo development
      of TR1 cells. CONCLUSIONS: These results show, for the first time, the potent in
      vivo capacity of naturally occurring human Tregs to control GvHD-inducing
      autologous T cells, and indicate that this xenogeneic in vivo model may provide a
      suitable platform to further explore the in vivo mechanisms of T-cell down
      regulation by naturally occurring human Tregs.

PMID- 17000689
TI  - The thalidomide analogue, CC-4047, induces apoptosis signaling and growth arrest
      in childhood acute lymphoblastic leukemia cells in vitro and in vivo.
AB  - PURPOSE: Thalidomide and its analogues have shown promise in the treatment of
      multiple myeloma but their therapeutic potential has not been evaluated in models
      of acute lymphoblastic leukemia (ALL). EXPERIMENTAL DESIGN: We assessed the
      effects of the thalidomide analogue, CC-4047, on the growth and apoptosis
      signaling of human B cell precursor (BCP) ALL cell lines and freshly obtained
      childhood BCP-ALL cells grown with or without stromal cells. In addition, we
      studied the effects of CC-4047 on the progression and dissemination of
      xenotransplanted human BCP-ALL cells in nonobese diabetic/severe combined
      immunodeficiency mice. RESULTS: CC-4047 reduced the proliferation of human BCP
      ALL cell lines in vitro. In contrast with the antileukemic effect of cytarabin,
      this was more pronounced when cell lines or freshly obtained childhood BCP-ALL
      cells were cocultured with stromal cells. CC-4047 induced the cleavage of caspase
      3, caspase-9, and poly(ADP-ribose) polymerase in stroma-cocultured BCP-ALL cells.
      The inhibition of tumor growth, caspase-3 cleavage, and reduced microvessel
      density was observed in nonobese diabetic/severe combined immunodeficiency mice
      inoculated s.c. with childhood BCP-ALL cells upon CC-4047 treatment. After i.v.
      BCP-ALL xenotransplantation, CC-4047 reduced splenic dissemination. CONCLUSIONS:
      The thalidomide analogue, CC-4047, displays profound cytostatic effects on stroma
      supported human ALL cells both in vitro and in vivo.

PMID- 17000690
TI  - The Ras inhibitor farnesylthiosalicylic acid as a potential therapy for
      neurofibromatosis type 1.
AB  - PURPOSE: Farnesylthiosalicylic acid (FTS) is a Ras inhibitor that dislodges all
      active Ras isoforms from the membrane. We assessed the ability of FTS to reverse
      the transformed phenotype of neurofibromatosis type 1 (NF1)-associated tumor cell
      lines of malignant peripheral nerve sheath tumor (MPNST). EXPERIMENTAL DESIGN:
      nf1 mutations were genotyped, allelic losses were analyzed, and neurofibromin
      expression levels were determined in MPNST cell lines ST88-14, S265P21, and 90-8.
      The effects of FTS on GTP-bound Ras (Ras-GTP) and its prominent downstream
      targets, as well as on cell morphology, anchorage-dependent and anchorage
      independent growth, and tumor growth in mice, were assessed. RESULTS: The MPNST
      cell lines were biallelic, NF1 inactive, and neurofibromin deficient. We show
      that FTS treatment shortened the relatively long duration of Ras activation and
      signaling to extracellular signal-regulated kinase, Akt, and RalA in all NF1
      deficient MPNST cell lines (NF1 cells) to that observed in a non-NF1, normally
      expressing neurofibromin MPNST cell line. These effects of FTS led to lower
      steady-state levels of Ras-GTP and its activated targets. Both anchorage
      dependent and anchorage-independent growth of NF1 cells were dose dependently
      inhibited by FTS, and the inhibition correlated positively with Ras-GTP levels.
      NF1 cells were found to possess strong actin stress fibers, and this phenotype
      was also corrected by FTS. NF1 tumor growth in a nude mouse model was inhibited
      by oral FTS. CONCLUSIONS: FTS treatment of NF1 cells normalized Ras-GTP levels,
      resulting in reversal of the transformed phenotype and inhibition of tumor
      growth. FTS may therefore be considered as a potential drug for the treatment of
      NF1.

PMID- 17000691
TI  - In vivo efficacy of STX213, a second-generation steroid sulfatase inhibitor, for
      hormone-dependent breast cancer therapy.
AB  - PURPOSE: Steroid sulfatase (STS) inhibitors that can decrease or prevent the
      biosynthesis of estrogenic steroids via the sulfatase route may play an important
      role in the treatment of breast cancer. We compare the in vivo efficacy of two
      potent STS inhibitors, STX64 and STX213, in a xenograft breast cancer model.
      EXPERIMENTAL DESIGN: MCF-7 cells stably expressing STS cDNA (MCF-7STS) were
      generated. Ovariectomized MF-1 female nude mice receiving s.c. injections of
      estradiol sulfate (E2S) and bearing both MCF-7STS and wild-type MCF-7 (MCF-7WT)
      tumors were orally treated with STX64 and STX213. Treatment was given for 49 days
      followed by a recovery period of 35 days in which animals received only E2S. Mice
      were weighed, and tumor measurements were taken weekly. RESULTS: STX64 and STX213
      exhibited potent STS inhibition in vivo. However, STX213 showed a greater
      duration of activity. In vehicle-treated nude mice receiving E2S, tumor volumes
      increased 5.5-fold for MCF-7WT and 3.8-fold for MCF-7STS after 49 days compared
      with day 0. MCF-7WT tumor growth was reduced by 56% by STX213 over the dosing
      period, and subsequent growth was retarded during the recovery period. All
      treatments fully inhibited growth of MCF-7STS tumors, and recovery of these
      tumors was significantly retarded (P<0.01). All compounds completely inhibited
      liver and tumor STS activity. Additionally, STS mRNA expression in the MCF-7STS
      tumors directly correlated with the corresponding STS enzyme activity.
      CONCLUSIONS: This study indicates that STS inhibitors attenuate hormone-dependent
      human breast cancer growth and therefore offer a potentially novel treatment for
      this condition.

PMID- 17000692
TI  - Human neural stem cells target experimental intracranial medulloblastoma and
      deliver a therapeutic gene leading to tumor regression.
AB  - PURPOSE: Medulloblastoma, a malignant pediatric brain tumor, is incurable in
      about one third of patients despite multimodal treatments. In addition, current
      therapies can lead to long-term disabilities. Based on studies of the extensive
      tropism of neural stem cells (NSC) toward malignant gliomas and the secretion of
      growth factors common to glioma and medulloblastoma, we hypothesized that NSCs
      could target medulloblastoma and be used as a cellular therapeutic delivery
      system. EXPERIMENTAL DESIGN: The migratory ability of HB1.F3 cells (an
      immortalized, clonal human NSC line) to medulloblastoma was studied both in vitro
      and in vivo. As proof-of-concept, we used HB1.F3 cells engineered to secrete the
      prodrug activating enzyme cytosine deaminase. We investigated the potential of
      human NSCs to deliver a therapeutic gene and reduce tumor growth. RESULTS: The
      migratory capacity of HB1.F3 cells was confirmed by an in vitro migration assay,
      and corroborated in vivo by injecting chloromethylbenzamido-Dil-labeled HB1.F3
      cells into the hemisphere contralateral to established medulloblastoma in nude
      mice. In vitro studies showed the therapeutic efficacy of HB1.F3-CD on Daoy cells
      in coculture experiments. In vitro therapeutic studies were conducted in which
      animals bearing intracranial medulloblastoma were injected ipsilaterally with
      HB1.F3-CD cells followed by systemic 5-flourocytosine treatment. Histologic
      analyses showed that human NSCs migrate to the tumor bed and its boundary,
      resulting in a 76% reduction of tumor volume in the treatment group (P<0.01).
      CONCLUSION: These studies show for the first time the potential of human NSCs as
      an effective delivery system to target and disseminate therapeutic agents to
      medulloblastoma.

PMID- 17000693
TI  - Benzethonium chloride: a novel anticancer agent identified by using a cell-based
      small-molecule screen.
AB  - PURPOSE: This study aims to identify a novel therapeutic agent for head and neck
      cancer and to evaluate its antitumor efficacy. EXPERIMENTAL DESIGN: A cell-based
      and phenotype-driven high-throughput screening of approximately 2,400
      biologically active or clinically used compounds was done using a tetrazolium
      based assay on FaDu (hypopharyngeal squamous cancer) and NIH 3T3 (untransformed
      mouse embryonic fibroblast) cells, with secondary screening done on C666-1
      (nasopharyngeal cancer) and GM05757 (primary normal human fibroblast) lines. The
      "hit" compound was assayed for efficacy in combination with standard therapeutics
      on a panel of human cancer cell lines. Furthermore, its mode of action (using
      transmission electron microscopy and flow cytometry) and its in vivo efficacy
      (using xenograft models) were evaluated. RESULTS: Benzethonium chloride was
      identified as a novel cancer-specific compound. For benzethonium (48-hour
      incubation), the dose required to reduce cell viability by 50% was 3.8 micromol/L
      in FaDu, 42.2 micromol/L in NIH 3T3, 5.3 micromol/L in C666-1, and 17.0
      micromol/L in GM05757. In vitro, this compound did not interfere with the effects
      of cisplatin, 5-fluorouracil, or gamma-irradiation. Benzethonium chloride induced
      apoptosis and activated caspases after 12 hours. Loss of mitochondrial membrane
      potential (DeltaPsiM) preceded cytosolic Ca2+ increase and cell death. In vivo,
      benzethonium chloride ablated the tumor-forming ability of FaDu cells, delayed
      the growth of xenograft tumors, and combined additively with local tumor
      radiation therapy. Evaluation of benzethonium chloride on the National Cancer
      Institute/NIH Developmental Therapeutics Program 60 human cancer cell lines
      revealed broad-range antitumor activity. CONCLUSIONS: This high-throughput
      screening identified a novel antimicrobial compound with significant broad
      spectrum anticancer activity.

PMID- 17000694
TI  - Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell
      lines in vitro and in vivo.
AB  - PURPOSE: The histone deacetylase inhibitor, suberoylanilide hydroxamic acid
      (SAHA), has multiple antitumor effects against a variety of human cancers.
      EXPERIMENTAL DESIGN: We treated several anaplastic and papillary thyroid cancer
      cell lines with SAHA to determine if it could inhibit the growth of these cells
      in vitro and in vivo. RESULTS: SAHA effectively inhibited 50% clonal growth of
      the anaplastic thyroid cancer cell lines, ARO and FRO, and the papillary thyroid
      cancer cell line, BHP 7-13, at 1.3x10(-7) to 5x10(-7) mol/L, doses that are
      achievable in patients. In concert with growth inhibition, SAHA down-regulated
      the expression of cyclin D1 and up-regulated levels of p21WAF1. Annexin V and
      cleavage of poly(ADP)ribose polymerase were both increased by exposure of the
      thyroid cancer cells to SAHA. Expression of the death receptor 5 (DR5) gene was
      also increased by SAHA, but the combination of the DR5 ligand, tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL), with SAHA had little effect
      compared with SAHA alone. Of note, the combination of paclitaxel, doxorubicin, or
      paraplatin with SAHA enhanced cell killing of the thyroid cancer cells. In
      addition, murine studies showed that SAHA administered daily by i.p. injection at
      100 mg/kg inhibited the growth of human thyroid tumor cells. CONCLUSION: Our data
      indicate that SAHA is a plausible adjuvant therapy for thyroid cancers.

PMID- 17000696
TI  - Bispecific antibody pretargeting of tumor neovasculature for improved systemic
      radiotherapy of solid tumors.
AB  - PURPOSE: Extra domain B (ED-B) fibronectin is a specific tumor matrix marker for
      targeting angiogenesis in solid tumors. In this study, the radiotherapeutic
      potential of the directly radioiodinated divalent anti-ED-B antibody fragment,
      L19 small immunoprotein (L19-SIP; 75,000 Da), was compared with a pretargeting
      approach using the bispecific antibody AP39xm679 (bsMAb; 75,000 Da). EXPERIMENTAL
      DESIGN: The bsMAb was prepared by coupling an anti-ED-B single-chain Fv (AP39) to
      the Fab' of the murine antibody m679, which binds to the small peptidic hapten
      histamine-succinyl-glycine (HSG). As an effector molecule for the pretargeting
      approach, the 111In-labeled HSG-DOTA complex was injected 25 or 41 hours after
      the bsMAb. The kinetics of both the iodinated bsMAb and the pretargeted 111In
      labeled HSG hapten were investigated in mice bearing human glioblastoma
      xenografts (U251) and compared with the kinetics and tumor accumulation of
      radioiodinated L19-SIP. 111In and 125I were used as surrogate marker for the
      therapeutic radioisotopes 90Y/177Lu and 131I, respectively. RESULTS: Tumor uptake
      of the pretargeted 111In-labeled peptide was significantly higher than 125I-L19
      SIP over 7 days. At the calculated maximally tolerated dose for each agent (with
      the kidney being the dose-limiting organ for pretargeting and the bone marrow for
      direct targeting), a mouse tumor dose of 146 Gy could be given by pretargeting
      versus 45 Gy delivered by the direct approach. CONCLUSIONS: These data suggest
      that pretargeting of ED-B with AP39xm679 and subsequent injection of the 90Y
      hapten-peptide would improve the therapeutic efficacy in solid tumors by >3-fold
      compared with directly radiolabeled 131I-L19-SIP.

PMID- 17000695
TI  - Interleukin 6, a nuclear factor-kappaB target, predicts resistance to docetaxel
      in hormone-independent prostate cancer and nuclear factor-kappaB inhibition by PS
      1145 enhances docetaxel antitumor activity.
AB  - PURPOSE: To investigate whether nuclear factor kappaB (NF-kappaB)/interleukin 6
      (IL-6) was linked to docetaxel response in human prostate cancer cell lines, and
      whether inhibition of NF-kappaB sensitized tumor cells to docetaxel. We also
      aimed to correlate IL-6 (as a surrogate marker of NF-kappaB) and docetaxel
      response in hormone-independent prostate cancer (HIPC) patients. EXPERIMENTAL
      DESIGN: Hormone-dependent (LNCaP) and hormone-independent (PC-3 and DU-145)
      prostate cancer cell lines were exposed to docetaxel alone or combined with the
      NF-kappaB inhibitor PS-1145 (an inhibitor of IkappaB kinase-2). Effects of dose,
      exposure time, and schedule dependence were assessed. Activation of NF-kappaB was
      assayed by electrophoresis mobility shift assay and luciferase reporter assay, IL
      6 levels by ELISA, and cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Cell cycle and apoptosis were assessed by
      fluorescence-activated cell sorting analysis. Apoptosis was also measured by
      detection of cleavage of poly(ADP-ribose) polymerase. In patients with metastatic
      HIPC receiving docetaxel-based chemotherapy, IL-6 serum levels were assayed
      before chemotherapy and every 3 to 4 weeks thereafter. RESULTS: PC-3 and DU-145
      cells had higher NF-kappaB activity, secreted more IL-6, and were more resistant
      to docetaxel than LNCaP cells. NF-kappaB activity was induced by docetaxel.
      Cotreatment with docetaxel and PS-1145 prevented docetaxel-induced NF-kappaB
      activation, reduced IL-6 production, and increased docetaxel effects on cell
      viability in PC-3 and DU-145 cells but not in LNCaP. Synergism with docetaxel and
      PS-1145, as assayed by median-effect principle, was observed in DU-145 and PC-3.
      In HIPC patients, pretreatment IL-6 serum levels correlated to prostate-specific
      antigen (PSA) response: median IL-6 level was 10.8+/-9.5 pg/mL in PSA responders
      versus 36.7+/-20.8 pg/mL (P=0.006) in nonresponders. A PSA response was also
      linked to a decline in IL-6 levels during treatment. Median overall survival was
      6.8 months in patients with high IL-6 versus 16.6 months in those with low IL-6
      (P=0.0007). On multivariate analysis, pretreatment IL-6 (P=0.05) was an
      independent prognostic factor for time to disease progression and survival.
      CONCLUSIONS: Inhibition of NF-kappaB emerges as an attractive strategy to enhance
      docetaxel response in prostate cancer. The interest of this view is further
      supported by a significant association between high IL-6 in sera of HIPC patients
      and decreased response to docetaxel.

PMID- 17000697
TI  - Polymorphisms of FAS and FAS ligand genes involved in the death pathway and risk
      and progression of squamous cell carcinoma of the head and neck.
AB  - PURPOSE: Alteration of the FAS/FAS ligand (FASLG) pathway regulating cell death
      may lead to cancer development, but the effects of functional promoter
      polymorphisms of the FAS and FASLG genes on risk of squamous cell carcinoma of
      the head and neck (SCCHN) are unknown. DESIGN: We genotyped the FAS -1377 G>A,
      FAS -670 A>G, FASLG -844 C>T, and FASLG IVS2nt -124 A>G polymorphisms in 721 case
      patients with SCCHN and 1,234 cancer-free non-Hispanic White control subjects
      frequency-matched by age and sex. Multivariate logistic regression was used to
      assess the adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS:
      Compared with the FAS -1377 GG and -670 AA genotypes, the FAS -1377 AA and -670
      (GG+AG) genotypes were associated with an increased risk of SCCHN (OR, 2.23; 95%
      CI, 1.07-4.64 and OR, 1.24; 95% CI, 1.01-1.52, respectively), whereas no risk of
      SCCHN was associated with any of the FASLG genotypes. When we used the combined
      FAS -1377 (GG+AG)/-670 AA genotypes as the reference, we found that the
      individuals carrying the FAS -1377 AA/-670 (GG+AG) had the highest risk (OR,
      2.69; 95% CI, 1.24-5.83), whereas individuals carrying genotypes other than FAS 
      1377 (GG+AG)/-670 AA had a higher risk of SCCHN (OR, 1.24; 95% CI, 1.01-1.52).
      Furthermore, the elevated risk was particularly evident for pharyngeal cancer
      with the larger tumors without regional lymph metastasis (OR, 1.77; 95% CI, 1.07
      2.94). CONCLUSIONS: The FAS (but not FASLG) polymorphisms seem to contribute to
      risk of developing SCCHN, particularly the pharyngeal cancer in non-Hispanic
      Whites. However, potential selection bias warrants future population-based
      studies to verify the findings.

PMID- 17000698
TI  - Aromatase inhibitors and postmenopausal breast cancer patients with tamoxifen
      induced endometrial pathology.

PMID- 17000699
TI  - Clearance mechanism of a mannosylated antibody-enzyme fusion protein used in
      experimental cancer therapy.
AB  - MFECP1 is a mannosylated antibody-enzyme fusion protein used in antibody-directed
      enzyme prodrug therapy (ADEPT). The antibody selectively targets tumor cells and
      the targeted enzyme converts a prodrug into a toxic drug. MFECP1 is obtained from
      expression in the yeast Pichia pastoris and produced to clinical grade. The P.
      pastoris-derived mannosylation of the fusion protein aids rapid normal tissue
      clearance required for successful ADEPT. The work presented provides evidence
      that MFECP1 is cleared by the endocytic and phagocytic mannose receptor (MR),
      which is known to bind to mannose-terminating glycans. MR-transfected fibroblast
      cells internalize MFECP1 as revealed by flow cytometry and confocal microscopy.
      Immunofluorescence microscopy shows that in vivo clearance in mice occurs
      predominantly by MR on liver sinusoidal endothelial cells, although MR is also
      expressed on adjacent Kupffer cells. In the spleen, MFECP1 is taken up by MR
      expressing macrophages residing in the red pulp and not by dendritic cells which
      are found in the marginal zone and white pulp. Clearance can be inhibited in vivo
      by the MR inhibitor mannan as shown by increased enzyme activities in blood. The
      work improves understanding of interactions of MFECP1 with normal tissue, shows
      that glycosylation can be exploited in the design of recombinant anticancer
      therapeutics and opens the ways for optimizing pharmacokinetics of mannosylated
      recombinant therapeutics.

PMID- 17000700
TI  - A case of resected huge ileocolonic mesenteric liposarcoma which responded to pre
      operative chemotherapy using doxorubicin, cisplatin and ifosfamide.
AB  - Primary mesenteric liposarcoma is a rare entity that has been reported only 14
      times in English literature. The treatment strategy for mesenteric liposarcoma
      is, if no distant metastases are detected, surgical resection with a wide
      surgical margin, often followed by radiation and/or adjuvant chemotherapy for
      high-risk patients. However, the efficacy of pre-operative chemotherapy is
      unknown. If the tumor is shrunk by pre-operative chemotherapy, we could achieve
      complete surgical resection, which is difficult when the tumor is too large or is
      invading neighboring organs. We herein describe a case of huge mesenteric
      liposarcoma that showed significant tumor shrinkage by pre-operative chemotherapy
      using doxorubicin, cisplatin and ifosfamide, allowing a margin-negative
      operation.

PMID- 17000701
TI  - A whole MEN1 gene deletion flanked by Alu repeats in a family with multiple
      endocrine neoplasia type 1.
AB  - Multiple endocrine neoplasia type 1 is an autosomal dominant cancer syndrome
      characterized by pituitary, parathyroid and enteropancreatic endocrine tumors,
      which is caused by germline mutations of the tumor suppressor gene MEN1. In the
      case reported here, the patient had family with this disease whose germline MEN1
      mutation was undetectable by conventional sequencing analysis. Further
      investigations involving polymorphism analyses, gene dose assay and nucleotide
      sequencing identified a large germline deletion of approximately 29 kilobase
      pairs spanning the whole MEN1 gene. The deletion was flanked by Alu repetitive
      sequences, suggesting unequal homologous recombination as the deletion mechanism.
      The polymorphism linkage data suggested that an asymptomatic son of the proband
      did not carry the family mutation. More direct evidence was obtained by gene dose
      assay and deletion-specific polymerase chain reaction, which demonstrated the
      normal MEN1 gene dosage and the absence of the deletion breakpoints in this
      asymptomatic subject and thus definitely excluded the possibility of disease
      predisposition.

PMID- 17000702
TI  - Clinical presentations and outcomes of surgical treatment of follicular variant
      of the papillary thyroid carcinomas.
AB  - BACKGROUND: The follicular variant of papillary thyroid carcinoma (FVPTC)
      presents with biological and morphological features similar to papillary thyroid
      carcinoma. Pre-operative diagnosis of FVPTC and its clinical course is important
      in identifying appropriate surgical procedures. METHODS: This study enrolled 85
      patients, 68 females (mean age 41.4+/-13.7 years) and 17 males (mean age 50.1+/
      12.3 years) with papillary thyroid carcinomas diagnosed as FVPTC. From the
      patient database at Chang Gung Medical Center (CGMC), 170 pure papillary thyroid
      carcinoma cases and 85 with minimally invasive follicular thyroid carcinomas of
      gender- and age-matched patients were randomly selected as control groups. All
      patients were categorized into high- and low-risk groups according to AMES
      criteria. RESULTS: Of the three groups, 7.1% (follicular), 11.8% (FVPTC) and
      34.1% (pure papillary thyroid carcinoma) of patients presented with lymph node or
      soft tissue invasion (P=0.0001). Additionally, 29.4, 11.8 and 2.4% of patients
      with follicular carcinoma, FVPTC and pure papillary thyroid carcinoma,
      respectively, presented with distant metastases at the time of diagnosis. Of the
      85 FVPTC cases, 75 underwent pre-operative fine needle aspiration cytology (FNAC)
      examination at CGMC. Only 11 cases were diagnosed pre-operatively with papillary
      thyroid carcinomas. Kaplan-Meier survival curves for these three groups
      demonstrated that follicular thyroid carcinoma had a prognosis worse than both
      papillary thyroid carcinomas. CONCLUSIONS: Most FVPTC cases were diagnosed as
      follicular neoplasm via pre-operative FNAC. In this study, FVPTC patients had a
      high ratio of distant metastases, few lymph node metastases and soft tissue
      invasion. Aggressive treatment was indicated for the high-risk FVPTC patients.

PMID- 17000703
TI  - C-terminal truncation and Parkinson's disease-associated mutations down-regulate
      the protein serine/threonine kinase activity of PTEN-induced kinase-1.
AB  - The Parkinson's disease (PD) causative PINK1 gene encodes a mitochondrial protein
      kinase called PTEN-induced kinase 1 (PINK1). The autosomal recessive pattern of
      inheritance of PINK1 mutations suggests that PINK1 is neuroprotective and
      therefore loss of PINK1 function causes PD. Indeed, overexpression of PINK1
      protects neuroblastoma cells from undergoing neurotoxin-induced apoptosis. As a
      protein kinase, PINK1 presumably exerts its neuroprotective effect by
      phosphorylating specific mitochondrial proteins and in turn modulating their
      functions. Towards elucidation of the neuroprotective mechanism of PINK1, we
      employed the baculovirus-infected insect cell system to express the recombinant
      protein consisting of the PINK1 kinase domain either alone [PINK1(KD)] or with
      the PINK1 C-terminal tail [PINK1(KD+T)]. Both recombinant enzymes preferentially
      phosphorylate the artificial substrate histone H1 exclusively at serine and
      threonine residues, demonstrating that PINK1 is indeed a protein serine/threonine
      kinase. Introduction of the PD-associated mutations, G386A and G409V
      significantly reduces PINK1(KD) kinase activity. Since Gly-386 and Gly-409 reside
      in the conserved activation segment of the kinase domain, the results suggest
      that the activation segment is a regulatory switch governing PINK1 kinase
      activity. We also demonstrate that PINK1(KD+T) is approximately 6-fold more
      active than PINK1(KD). Thus, in addition to the activation segment, the C
      terminal tail also contains regulatory motifs capable of governing PINK1 kinase
      activity. Finally, the availability of active recombinant PINK1 proteins permits
      future studies to search for mitochondrial proteins that are preferentially
      phosphorylated by PINK1. As these proteins are likely physiological substrates of
      PINK1, their identification will shed light on the mechanism of pathogenesis of
      PD.

PMID- 17000704
TI  - Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests
      functional redundancy.
AB  - The 22q11 deletion syndrome (22q11DS) is characterized by abnormal development of
      the pharyngeal apparatus. Mouse genetic studies have identified Tbx1 as a key
      gene in the etiology of the syndrome, in part, via interaction with the
      fibroblast growth factor (Fgf) genes. Three murine Fgfs, Fgf3, Fgf8 and Fgf10 are
      coexpressed in different combinations with Tbx1. They are all strongly
      downregulated in Tbx1-/- embryos, implicating epistatic interactions. Supporting
      this, Tbx1 and Fgf8 have been shown to genetically interact in the development of
      the fourth pharyngeal arch artery (PAA) and Fgf10 was identified to be a direct
      downstream target of Tbx1. To dissect the epistatic relationships of these genes
      during embryonic development and the molecular pathogenesis of the Tbx1 mutant
      phenotype, we generated Fgf10+/-;Tbx1+/- and Fgf3-/-;Tbx1+/- mice. Despite strong
      hypotheses that Fgf10 is the key gene downstream of Tbx1 in the development of
      the anterior heart field, we do not find evidence for genetic interaction between
      Tbx1 and Fgf10. Also, the Fgf3-/-;Tbx1+/- mutant mice do not show an additive
      phenotype. Furthermore, more severe defects do not occur in Fgf8+/-;Tbx1+/-
      mutants by crossing in the Fgf3 null allele. There is a possible additive effect
      only in PAA remodeling in the Fgf10+/-;Tbx1+/-;Fgf8+/- embryos. Our findings
      underscore the importance of potential functional redundancy with additional Fgfs
      in the development of the pharyngeal apparatus and cardiovascular system via
      Tbx1. This redundancy should be considered when looking at individual FGF genes
      as modifiers of 22q11DS.

PMID- 17000706
TI  - Search for low penetrance alleles for colorectal cancer through a scan of 1467
      non-synonymous SNPs in 2575 cases and 2707 controls with validation by kin-cohort
      analysis of 14 704 first-degree relatives.
AB  - To identify low penetrance susceptibility alleles for colorectal cancer (CRC), we
      genotyped 1467 non-synonymous SNPs mapping to 871 candidate cancer genes in 2575
      cases and 2707 controls. nsSNP selection was biased towards those predicted to be
      functionally deleterious. One SNP AKAP9 M463I remained significantly associated
      with CRC risk after stringent adjustment for multiple testing. Further SNPs
      associated with CRC risk included several previously reported to be associated
      with cancer risk including ATM F858L [OR=1.48; 95% confidence interval (CI): 1.06
      2.07] and P1054R (OR=1.42; 95% CI: 1.14-1.77) and MTHFR A222V (OR=0.82; 95% CI:
      0.69-0.97). To validate associations, we performed a kin-cohort analysis on the
      14 704 first-degree relatives of cases for each SNP associated at the 5% level in
      the case-control analysis employing the marginal maximum likelihood method to
      infer genotypes of relatives. Our observations support the hypothesis that
      inherited predisposition to CRC is in part mediated through polymorphic variation
      and identify a number of SNPs defining inter-individual susceptibility. We have
      made data from this analysis publicly available at
      http://www.icr.ac.uk/research/research_sections/cancer_genetics/cancer_genetics_t
      ams/molecular_and_population_genetics/software_and_databases/index.shtml in order
      to facilitate the identification of low penetrance CRC susceptibility alleles
      through pooled analyses.

PMID- 17000705
TI  - CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related
      maculopathy: AREDS and CHS cohorts and meta-analyses.
AB  - Age-related maculopathy (ARM) is an important cause of visual impairment in the
      elderly population. It is of crucial importance to identify genetic factors and
      their interactions with environmental exposures for this disorder. This study was
      aimed at investigating the CFH, ELOVL4, PLEKHA1 and LOC387715 genes in
      independent cohorts collected using different ascertainment schemes. The study
      used a case-control design with subjects originally recruited through the
      Cardiovascular Health Study (CHS) and the Age-Related Eye Disease Study (AREDS).
      CFH was significantly associated with ARM in both cohorts (P</=0.00001). A meta
      analysis confirmed that the risk allele in the heterozygous or homozygous state
      (OR, 2.4 and 6.2; 95% CI, 2.2-2.7 and 5.4-7.2, respectively) confers
      susceptibility. LOC387715 was also significantly associated with ARM in both
      cohorts (P</=0.00001) and a meta-analysis confirmed that the risk allele in the
      heterozygous and homozygous state (OR, 2.5 and 7.3; 95% CI, 2.2-2.9 and 5.7-9.4,
      respectively) confers susceptibility. Both CFH and LOC387715 showed an allele
      dose effect on the ARM risk, individuals homozygous at either locus were at more
      than two-fold risk compared to those heterozygous. PLEKHA1, which is closely
      linked to LOC387715, was significantly associated with ARM status in the AREDS
      cohort, but not the CHS cohort and ELOVL4 was not significantly associated with
      ARM in either cohort. Joint action of CFH and LOC387715 was best described by
      independent multiplicative effect without significant interaction in both
      cohorts. Interaction of both genes with cigarette smoking was insignificant in
      both cohorts. This study provides additional support for the CFH and LOC387715
      genes in ARM susceptibility via the evaluation of cohorts that had different
      ascertainment schemes regarding ARM status and through the meta-analyses.

PMID- 17000707
TI  - Evidence for unique association signals in SLE at the CD28-CTLA4-ICOS locus in a
      family-based study.
AB  - CD28, CTLA4 (cytotoxic T lymphocyte-associated protein 4) and ICOS (inducible T
      cell co-stimulator) are good candidate genes for systemic lupus erythematosus
      (SLE) because of their role in regulating T cell activation. CTLA4 inhibits CD28
      mediated T cell activation. CTLA4 is expressed on CD4+ and CD8+ activated T
      cells, and also B cells, but CD28 and ICOS are largely restricted to T cells. An
      interval encompassing the CD28-CTLA4-ICOS locus on chromosome 2q33 was linked to
      lupus in two genome-wide linkage scans. This large family-based association study
      in 532 UK SLE families represents the first high-density genetic screen of 80
      SNPs at this locus. There are seven haplotype blocks across the locus. In CTLA4,
      the strongest signal comes from two variants, located 2.1 kb downstream from the
      3'-UTR. These polymorphisms, rs231726 (SNP 43) and rs231726 (SNP 44), are in
      complete linkage disequilibrium (LD) (r(2)=1) and are associated with SLE
      P=0.0008 (GH) and P=0.01 (family-based association test). There is also a signal
      in the distal 3' flanking region of CTLA4/ICOS promoter (P=0.003). There was no
      confirmation of published associations for SLE in the promoter or coding region
      of CTLA4. These SLE risk alleles are more distal than those identified in Graves'
      disease and are in LD with Graves' disease protective alleles identified in both
      of these regions of CTLA4 (Ueda et al. 2003). These factors suggest an SLE
      specific pattern of association. The functional consequences of the associated
      polymorphisms are likely to influence CTLA4 expression, although it is possible
      that genetically modulated ICOS expression is involved in SLE susceptibility.

PMID- 17000708
TI  - FGF19 is a target for FOXC1 regulation in ciliary body-derived cells.
AB  - The forkhead C1 (FOXC1) transcription factor is involved in the development and
      regulation of several organs, including the eye, where FOXC1 alterations cause
      iris, trabecular meshwork and corneal anomalies. Using nickel agarose chromatin
      enrichment with human anterior segment cells, we previously identified the
      fibroblast growth factor 19 (FGF19) locus as a gene potentially regulated by
      FOXC1. Here, we demonstrate that FGF19 is a direct target of FOXC1 in the eye.
      FOXC1 positively regulates FGF19 expression in corneal and periocular mesenchymal
      cells in cell culture and in zebrafish embryos. Through the FGFR4 tyrosine
      kinase, FGF19 promotes MAPK phosphorylation in the developing and mature cornea.
      During development, loss of either FOXC1 or FGF19 results in complementary, but
      distinct, anterior segment dysgeneses. This study reveals an important role for
      FOXC1 in the direct regulation of the FGF19-FGFR4-MAPK pathway to promote both
      the development and maintenance of anterior segment structures within the eye.

PMID- 17000709
TI  - Make it boring: letter to the Journal of Public Health.

PMID- 17000710
TI  - Patient characteristics and hospital quality for colorectal cancer surgery.
AB  - OBJECTIVE: To assess associations of patient characteristics with quality-related
      characteristics of the hospitals where they were treated for colorectal cancer
      and the role of these associations in disparities in treatment quality affecting
      vulnerable patient groups or variations across health plans. SETTING: Population
      based cancer registry in California. PARTICIPANTS: A total of 38 237 patients
      diagnosed with stage I-III (non-metastatic) colorectal cancer in California
      between 1994 and 1998. METHODS: Registry data were linked with hospital discharge
      abstracts, US census data, and Medicare enrollment data. The associations of
      patients' sociodemographic, clinical, and geographic covariates with treatment at
      high-volume institutions were assessed with logistic regression. The associations
      of patients' covariates with the risk-adjusted 30-day mortality rates of the
      hospitals where they received surgery were tested with linear regression.
      RESULTS: Patients with more advanced tumor stage or more extensive comorbidity,
      those of Hispanic or Asian race/ethnicity, and those from less affluent
      communities were less likely to undergo surgery at high-volume institutions and
      were treated at hospitals with higher risk-adjusted 30-day postoperative
      mortality rates than those who were less severely ill, white, or more affluent,
      respectively (all P < 0.05). Black patients also received surgery at hospitals
      with above-average mortality. Among patients 65 years and older, Medicare managed
      care enrollees underwent surgery in higher-volume hospitals than Medicare fee-for
      service enrollees, and there was substantial variation in hospital volume and
      adjusted hospital mortality among Medicare managed-care plans. CONCLUSION:
      Improving access of sicker, poorer, and minority patients to high-quality
      hospitals for cancer surgery may improve their outcomes. Further study of
      processes affecting hospital referral is warranted.

PMID- 17000711
TI  - Trampoline injuries.
AB  - OBJECTIVE: To describe the mechanism, location and types of injury for all
      patients treated for trampoline-associated injuries at St Olav's University
      Hospital, Trondheim, Norway, from March 2001to October 2004. MATERIALS AND
      METHODS: Patients were identified from a National Injury Surveillance System. All
      patients were asked to complete a standard questionnaire at their first visit at
      the hospital. Most data were recorded prospectively, but data on the mechanism of
      injury, the number of participants on the trampoline at the time of injury, adult
      supervision and whether the activity occurred at school or in another organised
      setting were collected retrospectively. RESULTS: A total of 556 patients, 56%
      male and 44% female, were included. The mean age of patients was 11 (range 1-62)
      years. 77% of the injuries occurred on the body of the trampoline, including
      falls on to the mat, collisions with another jumper, falls on to the frame or the
      springs, and performing a somersault, whereas 22% of the people fell off the
      trampoline. In 74% of the cases, more than two people were on the trampoline,
      with as many as nine trampolinists noted at the time of injury. For children <11
      years, 22% had adult supervision when the injury occurred. The most common types
      of injuries were fractures (36%) and injury to ligaments (36%). Injuries to the
      extremities predominated (79%), and the lower extremities were the most commonly
      injured part of the body (44%). A ligament injury in the ankle was the most often
      reported diagnosis (20%), followed by an overstretching of ligaments in the neck
      (8%) and a fracture of the elbow (7%). Regarding cervical injuries, two patients
      had cervical fractures and one patient had an atlantoaxial subluxation. Three
      patients with fractures in the elbow region reported an ulnar nerve neuropathy.
      13% of the patients were hospitalised for a mean of 2.2 days. CONCLUSION:
      Trampolining can cause serious injuries, especially in the neck and elbow areas
      of young children. The use of a trampoline is a high-risk activity. However, a
      ban is not supported. The importance of having safety guidelines for the use of
      trampolines is emphasised.

PMID- 17000712
TI  - Influences of palatal side design and finishing on the wearability and retention
      of mouthguards.
AB  - OBJECTIVES: To examine the influences of design and finishing on mouthguard
      wearability and retention. MATERIALS AND METHODS: 17 students at the Dental
      Technician Institute at Osaka University School of Dentistry, Osaka, Japan,
      participated in this study after providing informed consent. For each student, a
      single-layer custom-made mouthguard was fabricated from a 3.8-mm-thick ethylene
      vinyl acetate sheet using a standardised procedure to obtain a precise fit. Each
      mouthguard was modified by changing the margin location and shape through five
      consecutive steps. At each step, questionnaires with a visual analogue scale
      regarding wearability (comfort, breathing, speaking, swallowing, lip closure,
      temporomandibular joint fatigue and swallowing) and retention were completed by
      subjects after wearing the mouthguard for 5 min. Statistical analyses were
      carried out among the steps using Wilcoxon's signed-rank test with a significance
      level of p<0.05. RESULTS: Significant improvements were found for comfort,
      breathing, speaking and swallowing by trimming the palatal margin to the cervical
      area, smooth finishing and occlusal adjustment of the mouthguard (p<0.01). No
      significant differences were found for retention throughout the procedure.
      CONCLUSIONS: Within the limitations of this experimental study, design and
      finishing at the palatal side appear to have significant influences on mouthguard
      wearability, but not retention.

PMID- 17000713
TI  - Can patients with McArdle's disease run?
AB  - Patients with McArdle's disease commonly adopt a sedentary lifestyle. This
      sedentary behaviour, however, usually worsens the limited exercise capacity of
      these patients. Although eccentric muscle work can be associated with
      rhabdomyolysis, supervised eccentric training with gradually increasing loads has
      important advantages compared with conventional concentric work, particularly for
      patients with a poor cardiorespiratory system. We report the beneficial effects
      (particularly, increased VO(2peak) (from 14.6 to 30.8 ml/kg/min) and increased
      gross muscle efficiency (from 13.8% to 17.2%)) induced by a supervised aerobic
      training programme of 7 months duration including 3-4 running sessions (< or =60
      min/session) per week in a 38-year-old patient. These preliminary data suggest
      the potential therapeutic value of this type of exercise in these patients.

PMID- 17000714
TI  - Muscle-specific creatine kinase gene polymorphism and running economy responses
      to an 18-week 5000-m training programme.
AB  - OBJECTIVE: To investigate the association between muscle-specific creatine kinase
      (CKMM) gene polymorphism and the effects of endurance training on running
      economy. METHODS: 102 biologically unrelated male volunteers from northern China
      performed a 5000-m running programme, with an intensity of 95-105% ventilatory
      threshold. The protocol was undertaken three times per week and lasted for 18
      weeks. Running economy indexes were determined by making the participants run on
      a treadmill before and after the protocol, and the A/G polymorphism in the 3'
      untranslated region of CKMM was detected by polymerase chain reaction-restricted
      fragment length polymorphism (NcoI restriction enzyme). RESULTS: Three expected
      genotypes for CKMM-NcoI (AA, AG and GG) were observed in the participants. After
      training, all running economy indexes declined markedly. Change in steady-state
      consumption of oxygen, change in steady-state consumption of oxygen by mean body
      weight, change in steady-state consumption of oxygen by mean lean body weight and
      change in ventilatory volume in AG groups were larger than those in AA and GG
      groups. CONCLUSIONS: The findings indicate that the CKMM gene polymorphism may
      contribute to individual running economy responses to endurance training.

PMID- 17000716
TI  - Tongue to palate contact during speech in subjects with and without a tongue
      thrust.
AB  - The aims of this study were to determine the location and movements of the tongue
      on the palate during pronunciation of Persian consonants and selected words in
      subjects with and without a tongue thrust (TT). Ten patients with a TT and 10
      control subjects, 9-13 years of age, matched for age, gender, ethnicity, type and
      severity of malocclusion, with no history of orthodontic treatment, surgery, or
      systemic disease were selected. Maxillary alginate impressions were taken to
      construct upper removable appliances with 12 electrodes. Fine wires connected the
      electrodes to a specially designed electropalatovision (EPU) device. The
      removable appliance was inserted in the upper arch and then the Persian
      consonants and some selected words were pronounced by both groups. An
      electromechanical marker was included on each electrode which showed the tongue
      movements on the palate. Tongue movements, the quantity of the tongue contacts,
      and the location of the tongue were compared using t- and Chi-square tests. In
      the TT group, the tongue had more contact with the palate on six electrodes (P <
      0.001). When pronouncing the consonants, the tongue made contact anteriorly on
      the palate in the TT group. The quantity of tongue contacts with the palate was
      similar in both groups. During pronunciation of selected words, the contact
      points of the tongue to the palate were similar in both groups.

PMID- 17000715
TI  - Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review.
AB  - Lung cancer is the most common malignancy in the Western world, and the main risk
      factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk
      associated with environmental factors. The glutathione S-transferase theta 1 gene
      (GSTT1) is a particularly attractive candidate for lung cancer susceptibility
      because of its involvement in the metabolism of polycyclic aromatic hydrocarbons
      found in tobacco smoke and of other chemicals, pesticides, and industrial
      solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10
      20%) than among Asians (50-60%). The authors present a meta- and a pooled
      analysis of case-control, genotype-based studies that examined the association
      between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for
      the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled
      analysis). No association was observed between GSTT1 deletion and lung cancer for
      Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12);
      for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In
      the pooled analysis, the odds ratios were not significant for either Asians (OR =
      0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No
      significant interaction was observed between GSTT1 and smoking on lung cancer,
      whereas GSTT1 appeared to modulate occupational-related lung cancer.

PMID- 17000717
TI  - Long-term follow-up of orthodontically treated deep bite patients.
AB  - The aim of this study was to evaluate the long-term stability of corrected deep
      bite and mandibular anterior crowding in a sample of 62 subjects (30 patients and
      32 controls). The patients began treatment at a mean age of 12.2 years (SD 1.56).
      The treatment consisted of non-extraction and fixed appliances in 23 subjects and
      functional appliances in seven. The treatment group was compared with the control
      group with normal molar occlusion, normal overjet and overbite, no crowding, and
      without an orthodontic treatment need. The registrations were made on four
      occasions: before treatment (T1), after treatment (T2), and at two long-term
      follow-ups (T3 and T4). Four registrations were also made in the control group.
      All measurements were undertaken on plaster models and lateral cephalograms.
      Treatment was found to have normalized the overbite and overjet and to have
      eliminated the space deficiency in the mandibular anterior region. At T4, there
      was a minor relapse in overbite in the treatment group (mean 0.8 mm). In the
      control group, the overbite underwent reverse development (bite opening by 0.7
      mm) during the same period. The available mandibular incisor space, however, was 
      0.9 mm in the treatment group and -1.8 mm in the control group. The long-term
      stability of the treatment results was thus good.

PMID- 17000718
TI  - p53-independent induction of rat hepatic Mdm2 following administration of
      phenobarbital and pregnenolone 16alpha-carbonitrile.
AB  - Murine double minute 2 (Mdm2) negatively regulates p53 by mediating its
      ubiquitination and proteosomal degradation, and Mdm2 is recognized as a proto
      oncogene. In the present study, hepatic gene expression patterns induced by
      phenobarbital (PB; 100 mg/kg) and pregnenolone 16alpha-carbonitrile (PCN, 100
      mg/kg) were evaluated in male and female Sprague-Dawley rats using Affymetrix Rat
      Genome U34A gene arrays. In addition to changes in the hepatic expression of well
      characterized drug-metabolizing enzymes, an increase in Mdm2 mRNA was observed
      with both compounds after single or repeat dosing (5 days). However, gene array
      analyses did not reveal changes in other p53-dependent genes, suggesting that
      induction of Mdm2 occurred in a p53-independent manner. Real-time polymerase
      chain reaction confirmed the microarray results, as PB increased Mdm2 mRNA
      approximately twofold after single or repeat doses in male and female rats. PCN
      treatment increased Mdm2 mRNA levels up to 5- and 12-fold in male and female
      rats, respectively, after 5 days of dosing. Hepatic Mdm2 protein levels were
      increased, and immunohistochemical evaluation of rat liver demonstrated nuclear
      localization of Mdm2, suggesting an interaction with p53. Consequently, p53
      protein levels were also decreased by approximately 35 and 50% after 5 days of PB
      and PCN treatment, respectively. In direct contrast to rats, PB and PCN (100
      mg/kg) did not induce Mdm2 mRNA in mouse liver after 5 days of dosing. Finally,
      although Mdm2 in mice and humans is reported to migrate electrophoretically as
      two proteins with molecular weights of 76 and 90 kDa, rat Mdm2 protein was
      detected primarily as a 120-kDa species. Follow-up experiments indicated that rat
      hepatic Mdm2 was subject to posttranslational modification with small ubiquitin
      modifying (SUMO) proteins. Although the molecular mechanisms controlling Mdm2
      induction by PB and PCN in rats have not yet been determined, these results
      suggest that early effects on cell cycle regulation, response to DNA damage or
      cell transformation may contribute to liver tumor development.

PMID- 17000719
TI  - Concerted evolution of duplicated control regions within an ostracod
      mitochondrial genome.
AB  - The luminescent marine ostracod Vargula hilgendorfii comprises distinct
      populations around the Japanese islands. Its mitochondrial DNA is unusual, with
      duplicated control regions (CRs; CR#1 and CR#2). We determined the sequences of
      ostracod CRs in 7 different populations. The sequences of CR#1 and CR#2 within
      any population were extremely similar, above 99.7%; moreover, their derived
      evolutionary tree indicates that the pairs of CRs have evolved in concert within
      each mitochondrial genome. These results suggest that an exact replication
      mechanism controls the concerted evolution of CRs.

PMID- 17000720
TI  - Helicobacter pylori VacA toxin promotes bacterial intracellular survival in
      gastric epithelial cells.
AB  - Helicobacter pylori colonizes the gastric epithelium of at least 50% of the
      world's human population, playing a causative role in the development of chronic
      gastritis, peptic ulcers, and gastric adenocarcinoma. Current evidence indicates
      that H. pylori can invade epithelial cells in the gastric mucosa. However,
      relatively little is known about the biology of H. pylori invasion and survival
      in host cells. Here, we analyze both the nature of and the mechanisms responsible
      for the formation of H. pylori's intracellular niche. We show that in AGS cells
      infected with H. pylori, bacterium-containing vacuoles originate through the
      fusion of late endocytic organelles. This process is mediated by the VacA
      dependent retention of the small GTPase Rab7. In addition, functional
      interactions between Rab7 and its downstream effector, Rab-interacting lysosomal
      protein (RILP), are necessary for the formation of the bacterial compartment
      since expression of mutant forms of RILP or Rab7 that fail to bind each other
      impaired the formation of this unique bacterial niche. Moreover, the VacA
      mediated sequestration of active Rab7 disrupts the full maturation of vacuoles as
      assessed by the lack of both colocalization with cathepsin D and degradation of
      internalized cargo in the H. pylori-containing vacuole. Based on these findings,
      we propose that the VacA-dependent isolation of the H. pylori-containing vacuole
      from bactericidal components of the lysosomal pathway promotes bacterial survival
      and contributes to the persistence of infection.

PMID- 17000721
TI  - Antibodies enhance interaction of Vibrio cholerae with intestinal M-like cells.
AB  - Intestinal M cells bear a receptor for secretory immunoglobulin A (IgA) (sIgA)
      facing the lumen of the epithelial surfaces. Cells bearing this receptor are also
      found throughout an experimental monolayer consisting of polarized Caco-2 cells,
      a colon adenocarcinoma cell line. The presence of antibodies (mainly sIgA) in the
      lumen of the small intestine led us to explore the participation of the sIgA
      receptor and antibodies in the interaction of Caco-2-associated M-like cells with
      the mucosal pathogen Vibrio cholerae. Here, we demonstrate that sIgA antibodies
      isolated from pooled healthy human colostrums, as well as IgG from pooled healthy
      human serum, can recognize V. cholerae. Furthermore, opsonization enhances M-like
      cell transcytosis of V. cholerae strains. We also show that the cholera toxin
      (CT) receptor ganglioside GM(1) colocalizes with the sIgA receptor in cells of
      the epithelial monolayer. Both sIgA and IgG antibodies compete for the attachment
      of soluble CT subunit B to immobilized GM(1). Our results indicate that in this
      in vitro model system of intestinal epithelia, human sIgA and IgG contribute to
      the uptake of V. cholerae by M-like cells, probably through an interaction with
      GM(1). Our results support previous findings of others showing that sIgA can act
      as an endogenous adjuvant and that sIgA is important for the antigen-sampling
      function of M cells.

PMID- 17000722
TI  - Should we inhibit type I interferons in sepsis?

PMID- 17000723
TI  - Potential source of Francisella tularensis live vaccine strain attenuation
      determined by genome comparison.
AB  - Francisella tularensis is a bacterial pathogen that causes the zoonotic disease
      tularemia and is important to biodefense. Currently, the only vaccine known to
      confer protection against tularemia is a specific live vaccine strain (designated
      LVS) derived from a virulent isolate of Francisella tularensis subsp. holarctica.
      The origin and source of attenuation of this strain are not known. To assist with
      the design of a defined live vaccine strain, we sought to determine the genetic
      basis of the attenuation of LVS. This analysis relied primarily on the comparison
      between the genome of LVS and Francisella tularensis holarctica strain FSC200,
      which differ by only 0.08% of their nucleotide sequences. Under the assumption
      that the attenuation was due to a loss of function(s), only coding regions were
      examined in this comparison. To complement this analysis, the coding regions of
      two slightly more distantly related Francisella tularensis strains were also
      compared against the LVS coding regions. Thirty-five genes show unique sequence
      variations predicted to alter the protein sequence in LVS compared to the other
      Francisella tularensis strains. Due to these polymorphisms, the functions of 15
      of these genes are very likely lost or impaired. Seven of these genes were
      demonstrated to be under stronger selective constraints, suggesting that they are
      the most probable to be the source of LVS attenuation and useful for a newly
      defined vaccine.

PMID- 17000724
TI  - Leishmania chagasi T-cell antigens identified through a double library screen.
AB  - Control of human visceral leishmaniasis in regions where it is endemic is
      hampered in part by limited accessibility to medical care and emerging drug
      resistance. There is no available protective vaccine. Leishmania spp. protozoa
      express multiple antigens recognized by the vertebrate immune system. Since there
      is not one immunodominant epitope recognized by most hosts, strategies must be
      developed to optimize selection of antigens for prevention and immunodiagnosis.
      For this reason, we generated a cDNA library from the intracellular amastigote
      form of Leishmania chagasi, the cause of South American visceral leishmaniasis.
      We employed a two-step expression screen of the library to systematically
      identify T-cell antigens and T-dependent B-cell antigens. The first step was
      aimed at identifying the largest possible number of clones producing an epitope
      containing polypeptide by screening with a pool of sera from Brazilians with
      documented visceral leishmaniasis. After removal of clones encoding heat shock
      proteins, positive clones underwent a second-step screen for their ability to
      cause proliferation and gamma interferon responses in T cells from immune mice.
      Six unique clones were selected from the second screen for further analysis. The
      corresponding antigens were derived from glutamine synthetase, a transitional
      endoplasmic reticulum ATPase, elongation factor 1gamma, kinesin K39, repetitive
      protein A2, and a hypothetical conserved protein. Humans naturally infected with
      L. chagasi mounted both cellular and antibody responses to these proteins.
      Preparations containing multiple antigens may be optimal for immunodiagnosis and
      protective vaccines.

PMID- 17000725
TI  - The frequency of BDCA3-positive dendritic cells is increased in the peripheral
      circulation of Kenyan children with severe malaria.
AB  - The ability of Plasmodium falciparum-infected erythrocytes to adhere to host
      endothelial cells via receptor molecules such as ICAM-1 and CD36 is considered a
      hallmark for the development of severe malaria syndromes. These molecules are
      also expressed on leukocytes such as dendritic cells. Dendritic cells are antigen
      presenting cells that are crucial for the initiation of adaptive immune
      responses. In many human diseases, their frequency and function is perturbed. We
      analyzed the frequency of peripheral blood dendritic cell subsets and the plasma
      concentrations of interleukin-10 (IL-10) and IL-12 in Kenyan children with severe
      malaria and during convalescence and related these parameters to the adhesion
      phenotype of the acute parasite isolates. The frequency of CD1c(+) dendritic
      cells in children with acute malaria was comparable to that in healthy controls,
      but the frequency of BDCA3(+) dendritic cells was significantly increased.
      Analysis of the adhesion phenotypes of parasite isolates revealed that adhesion
      to ICAM-1 was associated with the frequency of peripheral blood CD1c(+) dendritic
      cells, whereas the adhesion of infected erythrocytes to CD36 correlated with high
      concentrations of IL-10 and low concentrations of IL-12 in plasma.

PMID- 17000726
TI  - Mac-1+ cells are the predominant subset in the early hepatic lesions of mice
      infected with Francisella tularensis.
AB  - The cell composition of early hepatic lesions of experimental murine tularemia
      has not been characterized with specific markers. The appearance of multiple
      granulomatous-necrotic lesions in the liver correlates with a marked increase in
      the levels of serum alanine transferase and lactate dehydrogenase. Francisella
      tularensis, detected by specific antibodies, can be first noted by day 1 and
      becomes associated with the lesions by 5 days postinoculation. These lesions
      become necrotic, with some evidence of in situ apoptosis. The lesions do not
      contain B, T, or NK cells. Rather, the lesions are largely composed of two
      subpopulations of Mac-1(+) cells that are associated with the bacteria. Gr-1(+)
      Mac-1(+) immature myeloid cells and major histocompatibility complex class II
      positive (MHC-II(+)) Mac-1(+) macrophages were the most abundant cell phenotypes
      found in the granuloma and are likely major contributors in controlling the
      infection in its early stages. Our findings have shown that there is an early
      development of hepatic lesions where F. tularensis colocalizes with both Gr-1(+)
      Mac-1(+) and MHC-II(+) Mac-1(+) cells.

PMID- 17000727
TI  - Role of inducible nitric oxide synthase and NADPH oxidase in early control of
      Burkholderia pseudomallei infection in mice.
AB  - Infection with the soil bacterium Burkholderia pseudomallei can result in a
      variety of clinical outcomes, including asymptomatic infection. The initial
      immune defense mechanisms which might contribute to the various outcomes after
      environmental contact with B. pseudomallei are largely unknown. We have
      previously shown that relatively resistant C57BL/6 mice can restrict bacterial B.
      pseudomallei growth more efficiently within 1 day after infection than highly
      susceptible BALB/c mice. By using this model, our study aimed to investigate the
      role of macrophage-mediated effector mechanisms during early B. pseudomallei
      infection. Depletion of macrophages revealed an essential role of these cells in
      the early control of infection in BALB/c and C57BL/6 mice. Strikingly, the
      comparison of the anti-B. pseudomallei activity of bone marrow-derived
      macrophages (BMM) from C57BL/6 and BALB/c mice revealed an enhanced bactericidal
      activity of C57BL/6 BMM, particularly after gamma interferon (IFN-gamma)
      stimulation. In vitro experiments with C57BL/6 gp91phox-/- BMM showed an impaired
      intracellular killing of B. pseudomallei compared to experiments with wild-type
      cells, although C57BL/6 gp91phox-/- cells still exhibited substantial killing
      activity. The anti-B. pseudomallei activity of C57BL/6 iNOS-/- BMM was not
      impaired. C57BL/6 gp91phox-/- mice lacking a functional NADPH oxidase were more
      susceptible to infection, whereas C57BL/6 mice lacking inducible nitric oxide
      synthase (iNOS) did not show increased susceptibility but were slightly more
      resistant during the early phase of infection. Thus, our data suggest that IFN
      gamma-mediated but iNOS-independent anti-B. pseudomallei mechanisms of
      macrophages might contribute to the enhanced resistance of C57BL/6 mice compared
      to that of BALB/c mice in the early phase of infection.

PMID- 17000728
TI  - Borrelia burgdorferi complement regulator-acquiring surface protein 1 of the Lyme
      disease spirochetes is expressed in humans and induces antibody responses
      restricted to nondenatured structural determinants.
AB  - Borrelia burgdorferi complement regulator-acquiring surface protein 1 (CRASP-1),
      the dominant factor H and FHL-1-binding protein of the Lyme disease spirochete B.
      burgdorferi, is implicated in pathogen persistence and was recently reported to
      be nonimmunogenic in humans. Here we show that serum samples from Lyme disease
      patients contain antibodies with exclusive specificity for nondenatured
      structural determinants of CRASP-1.

PMID- 17000729
TI  - Identification of MglA-regulated genes reveals novel virulence factors in
      Francisella tularensis.
AB  - The facultative intracellular bacterium Francisella tularensis causes the
      zoonotic disease tularemia. F. tularensis resides within host macrophages in
      vivo, and this ability is essential for pathogenesis. The transcription factor
      MglA is required for the expression of several Francisella genes that are
      necessary for replication in macrophages and for virulence in mice. We
      hypothesized that the identification of MglA-regulated genes in the Francisella
      genome by transcriptional profiling of wild-type and mglA mutant bacteria would
      lead to the discovery of new virulence factors utilized by F. tularensis. A total
      of 102 MglA-regulated genes were identified, the majority of which were
      positively regulated, including all of the Francisella pathogenicity island (FPI)
      genes. We mutated novel MglA-regulated genes and tested the mutants for their
      ability to replicate and induce cytotoxicity in macrophages and to grow in mice.
      Mutations in MglA-regulated genes within the FPI (pdpB and cds2) as well as
      outside the FPI (FTT0989, oppB, and FTT1209c) were either attenuated or
      hypervirulent in macrophages compared to the wild-type strain. All of these
      mutants exhibited decreased fitness in vivo in competition experiments with wild
      type bacteria. We have identified five new Francisella virulence genes, and our
      results suggest that characterizations of additional MglA-regulated genes will
      yield further insights into the pathogenesis of this bacterium.

PMID- 17000730
TI  - Differential role of CbpA and PspA in modulation of in vitro CXC chemokine
      responses of respiratory epithelial cells to infection with Streptococcus
      pneumoniae.
AB  - Respiratory epithelial cells play an active part in the host response to
      respiratory pathogens, such as Streptococcus pneumoniae, by releasing chemokines
      responsible for neutrophil recruitment. In order to investigate the role of
      specific pneumococcal virulence factors in eliciting CXC chemokine responses,
      type II pneumocytes (A549) and nasopharyngeal cells (Detroit-562) were infected
      with S. pneumoniae D39 or mutants lacking choline-binding protein A (CbpA),
      pneumococcal surface protein A (PspA), or specific domains thereof. In response
      to wild-type D39, both A549 and Detroit-562 cells showed a significant increase
      in CXC chemokine mRNA and interleukin-8 protein. This response was increased
      twofold when a cbpA deletion mutant (DeltaCbpA) was used, suggesting that CbpA
      inhibits CXC chemokine induction. All three N-terminal domains of CbpA are
      required for this effect, as in-frame deletion of the respective region of cbpA
      had the same effect on the CXC chemokine response as deletion of cbpA altogether.
      Infection with a pspA deletion mutant (DeltaPspA) led to a twofold decrease in
      the CXC chemokine response of A549 but not Detroit-562 cells, compared to
      infection with D39 at 2 h. Thus, PspA appears to have the ability to stimulate
      early CXC chemokine release from A549 cells. Deletion of the region of pspA
      encoding the first N-terminal alpha-helical domain reduced the ability of S.
      pneumoniae to elicit a chemokine response to the same degree as deletion of pspA
      altogether. Thus, the N termini of CbpA and PspA exert differential effects on
      CXC chemokine induction in epithelial cells infected with S. pneumoniae.

PMID- 17000731
TI  - Pulse wave velocity and proteins regulating vascular calcification and bone
      mineralization in patients treated with peritoneal dialysis.

PMID- 17000732
TI  - Disseminated zygomycosis presenting as thyroid abscess in a renal allograft
      recipient.

PMID- 17000733
TI  - Long-term survival rates in haemodialysis patients treated with strict volume
      control.
AB  - METHODS: We analysed the survival of 218 patients (132 male, 86 female, age 48 +/
      15 years) who were treated in our dialysis units since we adopted the strategy
      of strict volume control without antihypertensive drugs. The mean observation
      period was 47 +/- 34 (6-140) months. Follow-up was ended because of death (57
      patients), transfer to another center (35 patients), continous ambulatory
      peritoneal dialysis (CAPD) (15 patients) or transplantation (23 patients), while
      88 were still under our treatment at the time of writing. RESULTS: Blood pressure
      (BP) decreased from a mean of 150 +/- 31/89 +/- 16 at the start to 121 +/- 14/75
      +/- 8 mmHg at the end of observation (P < 0.001). Only nine patients needed a
      drug (enalapril) to reach this goal. Cardiothoracic index (CTI) dropped from 0.50
      +/- 0.06 to 0.46 +/- 0.05 (P < 0.001). Interdialytic weight gain decreased from
      1440 +/- 360 to 930 +/- 240 g/day (P < 0.001). Mortality rate was 68, 2 per 1000
      patient-years, better than in most published series. There was a striking
      influence of age, but also of CTI and systolic BP on survival rate. Patients with
      CTI > or = 0.48 showed mortality 3.8 times higher than CTI < 0.48 (log rank P <
      0.001). Consequently, the mean CTI of the deceased patients was much higher
      (0.50) than the average of the group (0.46) while their mean BP (123 +/- 16/75 +/
      9 mmHg) was not significantly different from the other patients. We found no
      increased mortality at low-normal pressure levels (systolic BP between 100 and
      130 mmHg), but mortality was increased in small groups of patients whose
      pressures were lower or higher than these values. Thus, the curve, relating
      mortality to blood pressure was shifted markedly to the left. CONCLUSIONS: These
      results strongly suggest that the strategy of 'volume control', also when applied
      with conventional dialysis times, normalizes BP and increases survival of
      dialysis patients. Cardiomegaly, as evidenced on the chest X-ray despite normal
      BP, had a strong negative influence on survival. The large majority of the
      patients had low-normal BP after long periods of treatment and showed the lowest
      mortality, favouring the view that target BP should be lower than advised by most
      authors.

PMID- 17000734
TI  - Comparison of early renal function parameters for the prediction of 5-year graft
      survival after kidney transplantation.
AB  - BACKGROUND: Early graft function (EGF) has an enduring effect on the subsequent
      course after kidney transplantation. This study compares quantitative parameters
      of EGF for the prediction of graft survival. METHODS: We involved 300 consecutive
      transplant recipients from deceased donors from 1989 to 2005. Urine output during
      24 h post-transplant (UO), and serum creatinine after 1 week (Cr7) were taken for
      explanatory variables. We generated Kaplan-Meier (K-M) estimates of graft
      survival, by quintiles of the explanatory variable. Cox regression was applied to
      control for various recipient factors. RESULTS: K-M survival estimates indicate a
      threshold effect of UO and Cr7, which can dissect the risk of graft failure. The
      thresholds referring to the 2nd quintile correspond to a UO >630 ml and a Cr7
      <2.5 mg/dl and were associated with a proportional hazard ratio of 0.52 (95% CI
      0.33-0.84) and 0.34 (95% CI 0.18-0.65), respectively. Combining both of the
      parameters predicted a 5-year graft survival probability >90%, according to a
      hazard ratio of 0.21 (95% CI 0.09-0.46). Requirement of dialysis post-transplant
      lost its discriminatory power and was not a significant explanatory variable in
      the multivariate analysis. CONCLUSION: Routine parameters for monitoring of EGF
      display a threshold effect allowing accurate prediction of 5-year graft survival
      at the earliest point in time. The quantitative threshold levels for an optimum
      discriminatory power require validation in a larger, preferably multicentre
      database.

PMID- 17000735
TI  - Advanced computing for systems biology.
AB  - Systems biology is based on computational modelling and simulation of large
      networks of interacting components. Models may be intended to capture processes,
      mechanisms, components and interactions at different levels of fidelity. Input
      data are often large and geographically disperse, and may require the computation
      to be moved to the data, not vice versa. In addition, complex system-level
      problems require collaboration across institutions and disciplines. Grid
      computing can offer robust, scaleable solutions for distributed data, compute and
      expertise. We illustrate some of the range of computational and data requirements
      in systems biology with three case studies: one requiring large computation but
      small data (orthologue mapping in comparative genomics), a second involving
      complex terabyte data (the Visible Cell project) and a third that is both
      computationally and data-intensive (simulations at multiple temporal and spatial
      scales). Authentication, authorisation and audit systems are currently not well
      scalable and may present bottlenecks for distributed collaboration particularly
      where outcomes may be commercialised. Challenges remain in providing lightweight
      standards to facilitate the penetration of robust, scalable grid-type computing
      into diverse user communities to meet the evolving demands of systems biology.

PMID- 17000737
TI  - First VanD-Type vancomycin-resistant Enterococcus raffinosus isolate.

PMID- 17000738
TI  - Mutational analysis of class A and class B penicillin-binding proteins in
      Streptococcus gordonii.
AB  - High-molecular-weight (HMW) penicillin-binding proteins (PBPs) are divided into
      class A and class B PBPs, which are bifunctional
      transpeptidases/transglycosylases and monofunctional transpeptidases,
      respectively. We determined the sequences for the HMW PBP genes of Streptococcus
      gordonii, a gingivo-dental commensal related to Streptococcus pneumoniae. Five
      HMW PBPs were identified, including three class A (PBPs 1A, 1B, and 2A) and two
      class B (PBPs 2B and 2X) PBPs, by homology with those of S. pneumoniae and by
      radiolabeling with [3H]penicillin. Single and double deletions of each of them
      were achieved by allelic replacement. All could be deleted, except for PBP 2X,
      which was essential. Morphological alterations occurred after deletion of PBP 1A
      (lozenge shape), PBP 2A (separation defect and chaining), and PBP 2B (aberrant
      septation and premature lysis) but not PBP 1B. The muropeptide cross-link
      patterns remained similar in all strains, indicating that cross-linkage for one
      missing PBP could be replaced by others. However, PBP 1A mutants presented
      shorter glycan chains (by 30%) and a relative decrease (25%) in one monomer stem
      peptide. Growth rate and viability under aeration, hyperosmolarity, and
      penicillin exposure were affected primarily in PBP 2B-deleted mutants. In
      contrast, chain-forming PBP 2A-deleted mutants withstood better aeration,
      probably because they formed clusters that impaired oxygen diffusion. Double
      deletion could be generated with any PBP combination and resulted in more-altered
      mutants. Thus, single deletion of four of the five HMW genes had a detectable
      effect on the bacterial morphology and/or physiology, and only PBP 1B seemed
      redundant a priori.

PMID- 17000739
TI  - Molecular epidemiology of VIM-4 metallo-beta-lactamase-producing Pseudomonas sp.
      isolates in Hungary.
AB  - VIM metallo-beta-lactamase-producing serotype O11 or O12 Pseudomonas aeruginosa
      isolates infecting or colonizing 19 patients from seven hospitals in Hungary were
      characterized between October 2003 and November 2005. Macrorestriction analysis
      revealed the involvement of hospitals from three different towns in northwest
      Hungary in an outbreak caused by VIM-4-producing P. aeruginosa.

PMID- 17000740
TI  - Prevalence of Trichomonas vaginalis isolates with resistance to metronidazole and
      tinidazole.
AB  - Clinical isolates of Trichomonas vaginalis were obtained from women consecutively
      enrolled in a study of partner notification. Testing of susceptibility to
      metronidazole and tinidazole was performed. Resistance to metronidazole and
      tinidazole was present in 17/178 (9.6%) and 1/178 (0.56%) strains, respectively.
      In vitro resistance was poorly correlated with clinical response to treatment.

PMID- 17000741
TI  - Mutations in penicillin-binding protein (PBP) genes and in non-PBP genes during
      selection of penicillin-resistant Streptococcus gordonii.
AB  - Penicillin resistance in Streptococcus spp. involves multiple mutations in both
      penicillin-binding proteins (PBPs) and non-PBP genes. Here, we studied the
      development of penicillin resistance in the oral commensal Streptococcus
      gordonii. Cyclic exposure of bacteria to twofold-increasing penicillin
      concentrations selected for a progressive 250- to 500-fold MIC increase (from
      0.008 to between 2 and 4 microg/ml). The major MIC increase (> or = 35-fold) was
      related to non-PBP mutations, whereas PBP mutations accounted only for a 4- to 8
      fold additional increase. PBP mutations occurred in class B PBPs 2X and 2B, which
      carry a transpeptidase domain, but not in class A PBP 1A, 1B, or 2A, which carry
      an additional transglycosylase domain. Therefore, we tested whether inactivation
      of class A PBPs affected resistance development in spite of the absence of
      mutations. Deletion of PBP 1A or 2A profoundly slowed down resistance development
      but only moderately affected resistance in already highly resistant mutants (MIC
      = 2 to 4 microg/ml). Thus, class A PBPs might facilitate early development of
      resistance by stabilizing penicillin-altered peptidoglycan via
      transglycosylation, whereas they might be less indispensable in highly resistant
      mutants which have reestablished a penicillin-insensitive cell wall-building
      machinery. The contribution of PBP and non-PBP mutations alone could be
      individualized in DNA transformation. Both PBP and non-PBP mutations conferred
      some level of intrinsic resistance, but combining the mutations synergized them
      to ensure high-level resistance (> or = 2 microg/ml). The results underline the
      complexity of penicillin resistance development and suggest that inhibition of
      transglycosylase might be an as yet underestimated way to interfere with early
      resistance development.

PMID- 17000742
TI  - Analysis of antibiotic resistance genes in multidrug-resistant Acinetobacter sp.
      isolates from military and civilian patients treated at the Walter Reed Army
      Medical Center.
AB  - Military medical facilities treating patients injured in Iraq and Afghanistan
      have identified a large number of multidrug-resistant (MDR) Acinetobacter
      baumannii isolates. In order to anticipate the impact of these pathogens on
      patient care, we analyzed the antibiotic resistance genes responsible for the MDR
      phenotype in Acinetobacter sp. isolates collected from patients at the Walter
      Reed Army Medical Center (WRAMC). Susceptibility testing, PCR amplification of
      the genetic determinants of resistance, and clonality were determined. Seventy
      five unique patient isolates were included in this study: 53% were from
      bloodstream infections, 89% were resistant to at least three classes of
      antibiotics, and 15% were resistant to all nine antibiotics tested. Thirty-seven
      percent of the isolates were recovered from patients nosocomially infected or
      colonized at the WRAMC. Sixteen unique resistance genes or gene families and four
      mobile genetic elements were detected. In addition, this is the first report of
      bla(OXA-58)-like and bla(PER)-like genes in the U.S. MDR A. baumannii isolates
      with at least eight identified resistance determinants were recovered from 49 of
      the 75 patients. Molecular typing revealed multiple clones, with eight major
      clonal types being nosocomially acquired and with more than 60% of the isolates
      being related to three pan-European types. This report gives a "snapshot" of the
      complex genetic background responsible for antimicrobial resistance in
      Acinetobacter spp. from the WRAMC. Identifying genes associated with the MDR
      phenotype and defining patterns of transmission serve as a starting point for
      devising strategies to limit the clinical impact of these serious infections.

PMID- 17000743
TI  - Deferasirox, an iron-chelating agent, as salvage therapy for rhinocerebral
      mucormycosis.

PMID- 17000744
TI  - Molecular analysis of a chromosome-carried erm(B) gene and its flanking insertion
      points in Lactobacillus johnsonii G41.
AB  - An erm(B) gene carried on the Lactobacillus johnsonii G41 chromosome and the
      upstream and downstream regions were fully sequenced. Apparently, a 1,495-bp
      segment of pRE25 from Enterococcus faecalis carrying the erm(B) gene became
      inserted, by an unknown mechanism, into the L. johnsonii chromosome.

PMID- 17000745
TI  - General catalytic deficiency of hepatitis C virus RNA polymerase with an S282T
      mutation and mutually exclusive resistance towards 2'-modified nucleotide
      analogues.
AB  - The hepatitis C virus (HCV) RNA-dependent RNA polymerase NS5B is an important
      target for antiviral therapies. NS5B is able to initiate viral RNA synthesis de
      novo and then switch to a fast and processive RNA elongation synthesis mode. The
      nucleotide analogue 2'-C-methyl CTP (2'-C-Me-CTP) is the active metabolite of
      NM283, a drug currently in clinical phase II trials. The resistance mutation
      S282T can be selected in HCV replicon studies. Likewise, 2'-O-Me nucleotides are
      active both against the purified polymerase and in replicon studies. We have
      determined the molecular mechanism by which the S282T mutation confers resistance
      to 2'-modified nucleotide analogues. 2'-C-Me-CTP is no longer incorporated during
      the initiation step of RNA synthesis and is discriminated 21-fold during RNA
      elongation by the NS5B S282T mutant. Strikingly, 2'-O-methyl CTP sensitivity does
      not change during initiation, but the analogue is no longer incorporated during
      elongation. This mutually exclusive resistance mechanism suggests not only that
      "2'-conformer" analogues target distinct steps in RNA synthesis but also that
      these analogues have interesting potential in combination therapies. In addition,
      the presence of the S282T mutation induces a general cost in terms of polymerase
      efficiency that may translate to decreased viral fitness: natural nucleotides
      become 5- to 20-fold less efficiently incorporated into RNA by the NS5B S282T
      mutant. As in the case for human immunodeficiency virus, our results might
      provide a mechanistic basis for the rational combination of drugs for low-fitness
      viruses.

PMID- 17000746
TI  - Treatment and prevention of Staphylococcus epidermidis experimental biomaterial
      associated infection by bactericidal peptide 2.
AB  - Biomaterial-associated infections (BAI) are the major cause of failure of
      indwelling medical devices and are predominantly caused by staphylococci,
      especially Staphylococcus epidermidis. We investigated the in vitro microbicidal
      activity of the synthetic antimicrobial peptide bactericidal peptide 2 (BP2) and
      its efficacy in a murine model of S. epidermidis BAI. BP2 showed potent
      microbicidal activity at micromolar concentrations against a broad spectrum of
      microorganisms, including antibiotic-resistant bacteria. The staphylocidal
      activity of BP2 was not affected by physiological salt concentrations and was
      only slightly affected by the presence of human plasma. In the BAI model,
      injection of BP2 (5 mg/kg of body weight) 1 h after challenge with S. epidermidis
      resulted in an 80% reduction in the number of culture-positive implants and a 100
      fold reduction in survival of S. epidermidis in peri-implant tissue at 24 h
      postchallenge. When BP2 was injected along implants 3 h prior to bacterial
      challenge, the median numbers of CFU cultured from biomaterial implants and peri
      implant tissue were reduced by 85% and 90%, respectively. In conclusion, BP2 has
      potent, broad-spectrum in vitro microbicidal activity and showed potent in vivo
      activity in a murine model of S. epidermidis biomaterial-associated infection.

PMID- 17000747
TI  - Resistance mechanisms in an in vitro-selected amoxicillin-resistant strain of
      Helicobacter pylori.
AB  - We investigated the beta-lactam resistance mechanism(s) of an in vitro-selected
      amoxicillin-resistant Helicobacter pylori strain (AmoxR). Our results
      demonstrated that resistance is due to a combination of amino acid substitutions
      in penicillin binding protein 1 (PBP1), HopB, and HopC identified in AmoxR,
      resulting in decreased affinity of PBP1 for amoxicillin and decreased
      accumulation of penicillin.

PMID- 17000748
TI  - Long-term treatment with lopinavir-ritonavir induces a reduction in peripheral
      adipose depots in mice.
AB  - Highly active antiretroviral therapy (HAART) of human immunodeficiency virus
      infected patients is associated with adverse effects, such as lipodystrophy and
      hyperlipidemia. The lipodystrophic syndrome is characterized by a peripheral
      lipoatrophy and/or fat accumulation in the abdomen and neck. In order to get
      insights into the physiopathological mechanisms underlying this syndrome, we
      treated mice with protease inhibitors (PIs) over a long period of time. Although
      atazanavir-treated mice presented the same circulating triglyceride concentration
      as control mice, lopinavir-ritonavir-treated mice rapidly became
      hypertriglyceridemic, with triglyceride levels of 200 mg/dl, whereas control and
      atazanavir-treated animals had triglyceride levels of 80 mg/dl. These results
      obtained with mice reproduce the metabolic disorder observed in humans. White
      adipose tissue (WAT) was analyzed after 8 weeks of treatment. Compared to the
      control or atazanavir treatment, lopinavir-ritonavir treatment induced a
      significant 25% weight reduction in the peripheral inguinal WAT depot. By
      contrast, the profound epididymal WAT depot was not affected. This effect was
      associated with a 5.5-fold increase in SREBP-1c gene expression only in the
      inguinal depot. Our results demonstrate that the long-term treatment of mice with
      PIs constitutes an interesting experimental model with which some aspects of the
      lipoatrophy induced by HAART in humans may be studied.

PMID- 17000749
TI  - PromoterExplorer: an effective promoter identification method based on the
      AdaBoost algorithm.
AB  - MOTIVATION: Promoter prediction is important for the analysis of gene
      regulations. Although a number of promoter prediction algorithms have been
      reported in literature, significant improvement in prediction accuracy remains a
      challenge. In this paper, an effective promoter identification algorithm, which
      is called PromoterExplorer, is proposed. In our approach, we analyze the
      different roles of various features, that is, local distribution of pentamers,
      positional CpG island features and digitized DNA sequence, and then combine them
      to build a high-dimensional input vector. A cascade AdaBoost-based learning
      procedure is adopted to select the most 'informative' or 'discriminating'
      features to build a sequence of weak classifiers, which are combined to form a
      strong classifier so as to achieve a better performance. The cascade structure
      used for identification can also reduce the false positive. RESULTS:
      PromoterExplorer is tested based on large-scale DNA sequences from different
      databases, including the EPD, DBTSS, GenBank and human chromosome 22.
      Experimental results show that consistent and promising performance can be
      achieved.

PMID- 17000750
TI  - Software for dynamic analysis of tracer-based metabolomic data: estimation of
      metabolic fluxes and their statistical analysis.
AB  - MOTIVATION: Metabolic flux analysis of biochemical reaction networks using
      isotope tracers requires software tools that can analyze the dynamics of isotopic
      isomer (isotopomer) accumulation in metabolites and reveal the underlying kinetic
      mechanisms of metabolism regulation. Since existing tools are restricted by the
      isotopic steady state and remain disconnected from the underlying kinetic
      mechanisms, we have recently developed a novel approach for the analysis of
      tracer-based metabolomic data that meets these requirements. The present
      contribution describes the last step of this development: implementation of (i)
      the algorithms for the determination of the kinetic parameters and respective
      metabolic fluxes consistent with the experimental data and (ii) statistical
      analysis of both fluxes and parameters, thereby lending it a practical
      application. RESULTS: The C++ applications package for dynamic isotopomer
      distribution data analysis was supplemented by (i) five distinct methods for
      resolving a large system of differential equations; (ii) the 'simulated
      annealing' algorithm adopted to estimate the set of parameters and metabolic
      fluxes, which corresponds to the global minimum of the difference between the
      computed and measured isotopomer distributions; and (iii) the algorithms for
      statistical analysis of the estimated parameters and fluxes, which use the
      covariance matrix evaluation, as well as Monte Carlo simulations. An example of
      using this tool for the analysis of (13)C distribution in the metabolites of
      glucose degradation pathways has demonstrated the evaluation of optimal set of
      parameters and fluxes consistent with the experimental pattern, their range and
      statistical significance, and also the advantages of using dynamic rather than
      the usual steady-state method of analysis. AVAILABILITY: Software is available
      free from http://www.bq.ub.es/bioqint/selivanov.htm

PMID- 17000751
TI  - GATHER: a systems approach to interpreting genomic signatures.
AB  - MOTIVATION: Understanding the full meaning of the biology captured in molecular
      profiles, within the context of the entire biological system, cannot be achieved
      with a simple examination of the individual genes in the signature. To facilitate
      such an understanding, we have developed GATHER, a tool that integrates various
      forms of available data to elucidate biological context within molecular
      signatures produced from high-throughput post-genomic assays. RESULTS: Analyzing
      the Rb/E2F tumor suppressor pathway, we show that GATHER identifies critical
      features of the pathway. We further show that GATHER identifies common biology in
      a series of otherwise unrelated gene expression signatures that each predict
      breast cancer outcome. We quantify the performance of GATHER and find that it
      successfully predicts 90% of the functions over a broad range of gene groups. We
      believe that GATHER provides an essential tool for extracting the full value from
      molecular signatures generated from genome-scale analyses. AVAILABILITY: GATHER
      is available at http://gather.genome.duke.edu/

PMID- 17000752
TI  - Peptide length-based prediction of peptide-MHC class II binding.
AB  - MOTIVATION: Algorithms for predicting peptide-MHC class II binding are typically
      similar, if not identical, to methods for predicting peptide-MHC class I binding
      despite known differences between the two scenarios. We investigate whether
      representing one of these differences, the greater range of peptide lengths
      binding MHC class II, improves the performance of these algorithms. RESULTS: A
      non-linear relationship between peptide length and peptide-MHC class II binding
      affinity was identified in the data available for several MHC class II alleles.
      Peptide length was incorporated into existing prediction algorithms using one of
      several modifications: using regression to pre-process the data, using peptide
      length as an additional variable within the algorithm, or representing register
      shifting in longer peptides. For several datasets and at least two algorithms
      these modifications consistently improved prediction accuracy. AVAILABILITY:
      http://malthus.micro.med.umich.edu/Bioinformatics

PMID- 17000753
TI  - Modelling interaction sites in protein domains with interaction profile hidden
      Markov models.
AB  - MOTIVATION: Due to the growing number of completely sequenced genomes, functional
      annotation of proteins becomes a more and more important issue. Here, we describe
      a method for the prediction of sites within protein domains, which are part of
      protein-ligand interactions. As recently demonstrated, these sites are not
      trivial to detect because of a varying degree of conservation of their location
      and type within a domain family. RESULTS: The developed method for the prediction
      of protein-ligand interaction sites is based on a newly defined interaction
      profile hidden Markov model (ipHMM) topology that takes structural and sequence
      data into account. It is based on a homology search via a posterior decoding
      algorithm that yields probabilities for interacting sequence positions and
      inherits the efficiency and the power of the profile hidden Markov model (pHMM)
      methodology. The algorithm enhances the quality of interaction site predictions
      and is a suitable tool for large scale studies, which was already demonstrated
      for pHMMs. AVAILABILITY: The MATLAB-files are available on request from the first
      author.

PMID- 17000754
TI  - Small interfering RNA screens reveal enhanced cisplatin cytotoxicity in tumor
      cells having both BRCA network and TP53 disruptions.
AB  - RNA interference technology allows the systematic genetic analysis of the
      molecular alterations in cancer cells and how these alterations affect response
      to therapies. Here we used small interfering RNA (siRNA) screens to identify
      genes that enhance the cytotoxicity (enhancers) of established anticancer
      chemotherapeutics. Hits identified in drug enhancer screens of cisplatin,
      gemcitabine, and paclitaxel were largely unique to the drug being tested and
      could be linked to the drug's mechanism of action. Hits identified by screening
      of a genome-scale siRNA library for cisplatin enhancers in TP53-deficient HeLa
      cells were significantly enriched for genes with annotated functions in DNA
      damage repair as well as poorly characterized genes likely having novel functions
      in this process. We followed up on a subset of the hits from the cisplatin
      enhancer screen and validated a number of enhancers whose products interact with
      BRCA1 and/or BRCA2. TP53(+/-) matched-pair cell lines were used to determine if
      knockdown of BRCA1, BRCA2, or validated hits that associate with BRCA1 and BRCA2
      selectively enhances cisplatin cytotoxicity in TP53-deficient cells. Silencing of
      BRCA1, BRCA2, or BRCA1/2-associated genes enhanced cisplatin cytotoxicity
      approximately 4- to 7-fold more in TP53-deficient cells than in matched TP53 wild
      type cells. Thus, tumor cells having disruptions in BRCA1/2 network genes and
      TP53 together are more sensitive to cisplatin than cells with either disruption
      alone.

PMID- 17000755
TI  - Evolutionarily conserved role of nucleostemin: controlling proliferation of
      stem/progenitor cells during early vertebrate development.
AB  - Nucleostemin (NS) is a putative GTPase expressed preferentially in the nucleoli
      of neuronal and embryonic stem cells and several cancer cell lines. Transfection
      and knockdown studies indicated that NS controls the proliferation of these cells
      by interacting with the p53 tumor suppressor protein and regulating its activity.
      To assess the physiological role of NS in vivo, we generated a mutant mouse line
      with a specific gene trap event that inactivates the NS allele. The corresponding
      NS(-/-) embryos died around embryonic day 4. Analyses of NS mutant blastocysts
      indicated that NS is not required to maintain pluripotency, nucleolar integrity,
      or survival of the embryonic stem cells. However, the homozygous mutant
      blastocysts failed to enter S phase even in the absence of functional p53.
      Haploid insufficiency of NS in mouse embryonic fibroblasts leads to decreased
      cell proliferation. NS also functions in early amphibian development to control
      cell proliferation of neural progenitor cells. Our results show that NS has a
      unique ability, derived from an ancestral function, to control the proliferation
      rate of stem/progenitor cells in vivo independently of p53.

PMID- 17000756
TI  - Regulation of p53 localization and activity by Ubc13.
AB  - The abundance and activity of p53 are regulated largely by ubiquitin ligases.
      Here we demonstrate a previously undisclosed regulation of p53 localization and
      activity by Ubc13, an E2 ubiquitin-conjugating enzyme. While increasing p53
      stability, Ubc13 decreases p53 transcriptional activity and increases its
      localization to the cytoplasm, changes that require its ubiquitin-conjugating
      activity. Ubc13 elicits K63-dependent ubiquitination of p53, which attenuates
      Hdm2-induced polyubiquitination of p53. Ubc13 association with p53 requires an
      intact C-terminal domain of p53 and is markedly stronger with a p53 mutant that
      cannot tetramerize. Expression of Ubc13 in vivo increases the pool of monomeric
      p53, indicating that Ubc13 affects tetramerization of p53. Significantly, wild
      type but not mutant Ubc13 is associated with polysomes and enriches p53 within
      this fraction. In response to DNA damage, Ubc13 is no longer capable of
      facilitating p53 monomerization, in part due to a decrease in its own levels
      which is p53 dependent. Our findings point to a newly discerned mechanism
      important in the regulation of p53 organization, localization, and activity by
      Ubc13.

PMID- 17000757
TI  - Nuclear localization signal and protein context both mediate importin alpha
      specificity of nuclear import substrates.
AB  - The "classical" nuclear protein import pathway depends on importin alpha and
      importin beta. Importin alpha binds nuclear localization signal (NLS)-bearing
      proteins and functions as an adapter to access the importin beta-dependent import
      pathway. In humans, only one importin beta is known to interact with importin
      alpha, while six alpha importins have been described. Various experimental
      approaches provided evidence that several substrates are transported specifically
      by particular alpha importins. Whether the NLS is sufficient to mediate importin
      alpha specificity is unclear. To address this question, we exchanged the NLSs of
      two well-characterized import substrates, the seven-bladed propeller protein
      RCC1, preferentially transported into the nucleus by importin alpha3, and the
      less specifically imported substrate nucleoplasmin. In vitro binding studies and
      nuclear import assays revealed that both NLS and protein context contribute to
      the specificity of importin alpha binding and transport.

PMID- 17000758
TI  - Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine
      nucleotide exchange factor Dbs.
AB  - Dbs is a Rho-specific guanine nucleotide exchange factor (RhoGEF) with in vitro
      exchange activity specific for RhoA and Cdc42. Like many RhoGEF family members,
      the in vivo exchange activity of Dbs is restricted in a cell-specific manner.
      Here we report the characterization of a novel scaffold protein (designated cell
      cycle progression protein 1 [Ccpg1]) that interacts with Dbs and modulates its in
      vivo exchange specificity. When coexpressed in mammalian cells, Ccpg1 binds to
      the Dbl homology/pleckstrin homology domain tandem motif of Dbs and inhibits its
      exchange activity toward RhoA, but not Cdc42. Expression of Ccpg1 correlates with
      the ability of Dbs to activate endogenous RhoA in cultured cells, and suppression
      of endogenous Ccpg1 expression potentiates Dbs exchange activity toward RhoA. The
      isolated Dbs binding domain of Ccpg1 is not sufficient to suppress Dbs exchange
      activity on RhoA, thus suggesting a regulatory interaction. Ccpg1 mediates
      recruitment of endogenous Src kinase into Dbs-containing complexes and interacts
      with the Rho family member Cdc42. Collectively, our studies suggest that Ccpg1
      represents a new class of regulatory scaffold protein that can function as both
      an assembly platform for Rho protein signaling complexes and a regulatory protein
      which can restrict the substrate utilization of a promiscuous RhoGEF family
      member.

PMID- 17000759
TI  - Induction of gene silencing by hairpin RNA expression in Tetrahymena thermophila
      reveals a second small RNA pathway.
AB  - Unlike in other eukaryotes, in which it causes gene silencing, RNA interference
      (RNAi) has been linked to programmed DNA deletion in the ciliate Tetrahymena
      thermophila. Here we have developed an efficient method to inducibly express
      double-stranded RNA hairpins and demonstrated that they cause gene silencing
      through targeted mRNA degradation in all phases of the life cycle, including
      growth, starvation, and mating. This technique offers a new tool for gene
      silencing in this model organism. Induction of RNA hairpins causes dramatic
      upregulation of Dicer and Argonaute family genes, revealing a system capable of
      rapidly responding to double-stranded RNA. These hairpins are processed into 23-
      to 24-nucleotide (nt) small RNAs, which are distinctly different from the 28- to
      30-nt small RNAs known to be associated with DNA deletion. Thus, two different
      small RNA pathways appear to be responsible for gene silencing and DNA deletion.
      Surprisingly, expression of the RNA hairpin also causes targeted DNA deletion
      during conjugation, although at low efficiencies, which suggests a possible
      crossover of these two molecular paths.

PMID- 17000761
TI  - The microphthalmia-associated transcription factor Mitf interacts with beta
      catenin to determine target gene expression.
AB  - Commitment to the melanocyte lineage is characterized by the onset of expression
      of the microphthalmia-associated transcription factor (Mitf). This transcription
      factor plays a fundamental role in melanocyte development and maintenance and
      seems to be crucial for the survival of malignant melanocytes. Furthermore, Mitf
      has been shown to be involved in cell cycle regulation and to play important
      functions in self-renewal and maintenance of melanocyte stem cells. Although
      little is known about how Mitf regulates these various processes, one possibility
      is that Mitf interacts with other regulators. Here we show that Mitf can interact
      directly with beta-catenin, the key mediator of the canonical Wnt signaling
      pathway. The Wnt signaling pathway plays a critical role in melanocyte
      development and is intimately involved in triggering melanocyte stem cell
      proliferation. Significantly, constitutive activation of this pathway is a
      feature of a number of cancers including malignant melanoma. Here we show that
      Mitf can redirect beta-catenin transcriptional activity away from canonical Wnt
      signaling-regulated genes toward Mitf-specific target promoters to activate
      transcription. Thus, by a feedback mechanism, Mitf can diversify the output of
      canonical Wnt signaling to enhance the repertoire of genes regulated by beta
      catenin. Our results reveal a novel mechanism by which Wnt signaling and beta
      catenin activate gene expression, with significant implications for our
      understanding of both melanocyte development and melanoma.

PMID- 17000762
TI  - Efficient incorporation of multiple selenocysteines involves an inefficient
      decoding step serving as a potential translational checkpoint and ribosome
      bottleneck.
AB  - Selenocysteine is incorporated into proteins via "recoding" of UGA from a stop
      codon to a sense codon, a process that requires specific secondary structures in
      the 3' untranslated region, termed selenocysteine incorporation sequence (SECIS)
      elements, and the protein factors that they recruit. Whereas most selenoprotein
      mRNAs contain a single UGA codon and a single SECIS element, selenoprotein P
      genes encode multiple UGAs and two SECIS elements. We have identified
      evolutionary adaptations in selenoprotein P genes that contribute to the
      efficiency of incorporating multiple selenocysteine residues in this protein. The
      first is a conserved, inefficiently decoded UGA codon in the N-terminal region,
      which appears to serve both as a checkpoint for the presence of factors required
      for selenocysteine incorporation and as a "bottleneck," slowing down the progress
      of elongating ribosomes. The second adaptation involves the presence of introns
      downstream of this inefficiently decoded UGA which confer the potential for
      nonsense-mediated decay when factors required for selenocysteine incorporation
      are limiting. Third, the two SECIS elements in selenoprotein P mRNA function with
      differing efficiencies, affecting both the rate and the efficiency of decoding
      different UGAs. The implications for how these factors contribute to the decoding
      of multiple selenocysteine residues are discussed.

PMID- 17000760
TI  - LZTS2 is a novel beta-catenin-interacting protein and regulates the nuclear
      export of beta-catenin.
AB  - Beta-catenin plays multiple roles in cell-cell adhesion and Wnt signal
      transduction. Through the Wnt signal, the cellular level of beta-catenin is
      constitutively regulated by the multicomponent destruction complex containing
      glycogen synthase kinase 3beta, axin, and adenomatous polyposis coli. Here, we
      present multiple lines of evidence to demonstrate that LZTS2 (lucine zipper tumor
      suppressor 2) interacts with beta-catenin, represses the transactivation of beta
      catenin, and affects the subcellular localization of beta-catenin. The LZTS2 gene
      is located at 10q24.3, which is frequently lost in a variety of human tumors. A
      functional nuclear export signal (NES) was identified in the C terminus of the
      protein (amino acids 631 to 641). Appending this motif to green fluorescent
      protein (GFP) induced nuclear exclusion of the GFP fusion protein. However,
      introducing point mutations in either one or two leucine residues of this NES
      sequence abolished the nuclear exclusion of the LZTS2 protein. The nuclear export
      of LZTS2 can be blocked by leptomycin B (LMB), an inhibitor of the CRM1/exportin
      alpha pathway. Intriguingly, beta-catenin colocalizes with LZTS2 in the cytoplasm
      of cells in the absence of LMB but in the nuclei of cells in the presence of LMB.
      Increasing the LZTS2 protein in cells reduces the level of nuclear beta-catenin
      in SW480 cells. Taken together, these data demonstrate that LZTS2 is a beta
      catenin-interacting protein that can modulate beta-catenin signaling and
      localization.

PMID- 17000763
TI  - Nucleostemin delays cellular senescence and negatively regulates TRF1 protein
      stability.
AB  - Nucleostemin (NS) encodes a nucleolar GTP-binding protein highly enriched in the
      stem cells and cancer cells. To determine its biological activity in vivo, we
      generated NS loss- and gain-of-function mouse models. The embryogenesis of
      homozygous NS-null (NS(-/-)) mice was aborted before the blastula stage. Although
      the growth and fertility of heterozygous NS-null (NS(+/-)) mice appeared normal,
      NS(+/-) mouse embryonic fibroblasts (MEFs) had fewer NS proteins, a lower
      population growth rate, and higher percentages of senescent cells from passage 5
      (P5) to P7 than their wild-type littermates. Conversely, transgenic
      overexpression of NS could rescue the NS(-/-) embryo in a dose-dependent manner,
      increase the population growth rate, and reduce the senescent percentage of MEFs.
      Cell cycle analyses revealed increased pre-G1 percentages in the late-passage
      NS(+/-) MEF cultures compared to the wild-type cultures. We demonstrated that NS
      could interact with telomeric repeat-binding factor 1 (TRF1) and enhance the
      degradation but not the ubiquitination of the TRF1 protein, which negatively
      regulates telomere length and is essential for early embryogenesis. This work
      demonstrates the roles of NS in establishing early embryogenesis and delaying
      cellular senescence of MEFs and reveals a mechanism of a NS-regulated degradation
      of TRF1.

PMID- 17000764
TI  - Dimerization of the I kappa B kinase-binding domain of NEMO is required for tumor
      necrosis factor alpha-induced NF-kappa B activity.
AB  - Previous studies have demonstrated that peptides corresponding to a six-amino
      acid NEMO-binding domain from the C terminus of IkappaB kinase alpha (IKKalpha)
      and IKKbeta can disrupt the IKK complex and block NF-kappaB activation. We have
      now mapped and characterized the corresponding amino-terminal IKK-binding domain
      (IBD) of NEMO. Peptides corresponding to the IBD were efficiently recruited to
      the IKK complex but displayed only a weak inhibitory potential on cytokine
      induced NF-kappaB activity. This is most likely due to the formation of sodium
      dodecyl sulfate- and urea-resistant NEMO dimers through a dimerization domain at
      the amino terminus of NEMO that overlaps with the region responsible for binding
      to IKKs. Mutational analysis revealed different alpha-helical subdomains within
      an amino-terminal coiled-coil region are important for NEMO dimerization and
      IKKbeta binding. Furthermore, NEMO dimerization is required for the tumor
      necrosis factor alpha-induced NF-kappaB activation, even when interaction with
      the IKKs is unaffected. Hence, our data provide novel insights into the role of
      the amino terminus of NEMO for the architecture of the IKK complex and its
      activation.

PMID- 17000765
TI  - The Ral/exocyst effector complex counters c-Jun N-terminal kinase-dependent
      apoptosis in Drosophila melanogaster.
AB  - Ral GTPase activity is a crucial cell-autonomous factor supporting tumor
      initiation and progression. To decipher pathways impacted by Ral, we have
      generated null and hypomorph alleles of the Drosophila melanogaster Ral gene. Ral
      null animals were not viable. Reduced Ral expression in cells of the sensory
      organ lineage had no effect on cell division but led to postmitotic cell-specific
      apoptosis. Genetic epistasis and immunofluorescence in differentiating sensory
      organs suggested that Ral activity suppresses c-Jun N-terminal kinase (JNK)
      activation and induces p38 mitogen-activated protein (MAP) kinase activation.
      HPK1/GCK-like kinase (HGK), a MAP kinase kinase kinase kinase that can drive JNK
      activation, was found as an exocyst-associated protein in vivo. The exocyst is a
      Ral effector, and the epistasis between mutants of Ral and of msn, the fly
      ortholog of HGK, suggest the functional relevance of an exocyst/HGK interaction.
      Genetic analysis also showed that the exocyst is required for the execution of
      Ral function in apoptosis. We conclude that in Drosophila Ral counters apoptotic
      programs to support cell fate determination by acting as a negative regulator of
      JNK activity and a positive activator of p38 MAP kinase. We propose that the
      exocyst complex is Ral executioner in the JNK pathway and that a cascade from Ral
      to the exocyst to HGK would be a molecular basis of Ral action on JNK.

PMID- 17000766
TI  - The Hsp90 cochaperone p23 is essential for perinatal survival.
AB  - The functions of molecular chaperones have been extensively investigated
      biochemically in vitro and genetically in bacteria and yeast. We have embarked on
      a functional genomic analysis of the Hsp90 chaperone machine in the mouse by
      disrupting the p23 gene using a gene trap approach. p23 is an Hsp90 cochaperone
      that is thought to stabilize Hsp90-substrate complexes and, independently, to act
      as the cytosolic prostaglandin E2 synthase. Gene deletions in budding and fission
      yeasts and knock-down experiments with the worm have not revealed any clear in
      vivo requirements for p23. We find that p23 is not essential for overall prenatal
      development and morphogenesis of the mouse, which parallels the observation that
      it is dispensable for proliferation in yeast. In contrast, p23 is absolutely
      necessary for perinatal survival. Apart from an incompletely formed skin barrier,
      the lungs of p23 null embryos display underdeveloped airspaces and substantially
      reduced expression of surfactant genes. Correlating with the known function of
      glucocorticoids in promoting lung maturation and the role of p23 in the assembly
      of a hormone-responsive glucocorticoid receptor-Hsp90 complex, p23 null
      fibroblast cells have a defective glucocorticoid response. Thus, p23 contributes
      a nonredundant, temporally restricted, and tissue-specific function during mouse
      development.

PMID- 17000767
TI  - Ribosomal protein S6 gene haploinsufficiency is associated with activation of a
      p53-dependent checkpoint during gastrulation.
AB  - Nascent ribosome biogenesis is required during cell growth. To gain insight into
      the importance of this process during mouse oogenesis and embryonic development,
      we deleted one allele of the ribosomal protein S6 gene in growing oocytes and
      generated S6-heterozygous embryos. Oogenesis and embryonic development until
      embryonic day 5.5 (E5.5) were normal. However, inhibition of entry into M phase
      of the cell cycle and apoptosis became evident post-E5.5 and led to
      perigastrulation lethality. Genetic inactivation of p53 bypassed this checkpoint
      and prolonged development until E12.5, when the embryos died, showing decreased
      expression of D-type cyclins, diminished fetal liver erythropoiesis, and
      placental defects. Thus, a p53-dependent checkpoint is activated during
      gastrulation in response to ribosome insufficiency to prevent improper execution
      of the developmental program.

PMID- 17000768
TI  - A gene-specific requirement for FACT during transcription is related to the
      chromatin organization of the transcribed region.
AB  - The FACT complex stimulates transcription elongation on nucleosomal templates. In
      vivo experiments also involve FACT in the reassembly of nucleosomes traversed by
      RNA polymerase II. Since several features of chromatin organization vary
      throughout the genome, we wondered whether FACT is equally required for all
      genes. We show in this study that the in vivo depletion of Spt16, one of the
      subunits of Saccharomyces cerevisiae FACT, strongly affects transcription of
      three genes, GAL1, PHO5, and Kluyveromyces lactis LAC4, which exhibit positioned
      nucleosomes at their transcribed regions. In contrast, showing a random
      nucleosome structure, YAT1 and Escherichia coli lacZ are only mildly influenced
      by Spt16 depletion. We also show that the effect of Spt16 depletion on GAL1
      expression is suppressed by a histone mutation and that the insertion of a GAL1
      fragment, which allows the positioning of two nucleosomes, at the 5' end of YAT1
      makes the resulting transcription unit sensitive to Spt16 depletion. These
      results indicate that FACT requirement for transcription depends on the chromatin
      organization of the 5' end of the transcribed region.

PMID- 17000769
TI  - Recruitment of the nucleotide excision repair endonuclease XPG to sites of UV
      induced dna damage depends on functional TFIIH.
AB  - The structure-specific endonuclease XPG is an indispensable core protein of the
      nucleotide excision repair (NER) machinery. XPG cleaves the DNA strand at the 3'
      side of the DNA damage. XPG binding stabilizes the NER preincision complex and is
      essential for the 5' incision by the ERCC1/XPF endonuclease. We have studied the
      dynamic role of XPG in its different cellular functions in living cells. We have
      created mammalian cell lines that lack functional endogenous XPG and stably
      express enhanced green fluorescent protein (eGFP)-tagged XPG. Life cell imaging
      shows that in undamaged cells XPG-eGFP is uniformly distributed throughout the
      cell nucleus, diffuses freely, and is not stably associated with other nuclear
      proteins. XPG is recruited to UV-damaged DNA with a half-life of 200 s and is
      bound for 4 min in NER complexes. Recruitment requires functional TFIIH, although
      some TFIIH mutants allow slow XPG recruitment. Remarkably, binding of XPG to
      damaged DNA does not require the DDB2 protein, which is thought to enhance damage
      recognition by NER factor XPC. Together, our data present a comprehensive view of
      the in vivo behavior of a protein that is involved in a complex chromatin
      associated process.

PMID- 17000770
TI  - Normal establishment of epithelial tight junctions in mice and cultured cells
      lacking expression of ZO-3, a tight-junction MAGUK protein.
AB  - ZO-1, ZO-2, and ZO-3 are closely related MAGUK family proteins that localize at
      the cytoplasmic surface of tight junctions (TJs). ZO-1 and ZO-2 are expressed in
      both epithelia and endothelia, whereas ZO-3 is exclusively expressed in
      epithelia. In spite of intensive studies of these TJ MAGUKs, our knowledge of
      their functions in vivo, especially those of ZO-3, is still fragmentary. Here, we
      have generated mice, as well as F9 teratocarcinoma cell lines, that do not
      express ZO-3 by homologous recombination. Unexpectedly, ZO-3(-/-) mice were
      viable and fertile, and rigorous phenotypic analyses identified no significant
      abnormalities. Moreover, ZO-3-deficient F9 teratocarcinoma cells differentiated
      normally into visceral endoderm epithelium-like cells in the presence of retinoic
      acid. These cells had a normal epithelial appearance, and the molecular
      architecture of their TJs did not appear to be affected, except that TJ
      localization of ZO-2 was upregulated. Suppression of ZO-2 expression by RNA
      interference in ZO-3(-/-) cells, however, did not affect the architecture of TJs.
      Furthermore, the speed with which TJs formed after a Ca(2+) switch was
      indistinguishable between wild-type and ZO-3(-/-) cells. These findings indicate
      that ZO-3 is dispensable in vivo in terms of individual viability, epithelial
      differentiation, and the establishment of TJs, at least in the laboratory
      environment.

PMID- 17000771
TI  - Upf1/Upf2 regulation of 3' untranslated region splice variants of AUF1 links
      nonsense-mediated and A+U-rich element-mediated mRNA decay.
AB  - AUF1 is an RNA-binding protein that targets mRNAs containing A+U-rich elements
      (AREs) for rapid cytoplasmic turnover. Alternative pre-mRNA splicing produces
      five variants of AUF1 mRNA that differ in the composition of their 3'
      untranslated regions (3'-UTRs). Previous work suggested that this heterogeneity
      in 3'-UTR sequence could regulate AUF1 expression by two potential mechanisms.
      First, AUF1 may regulate its own expression by binding to AREs in 3'-UTR splice
      variants that retain intron 9. The second potential mechanism, and the focus of
      this report, is regulation of a subset of 3'-UTR splice variants by the nonsense
      mediated mRNA decay (NMD) pathway. Two of the five AUF1 mRNA 3'-UTR variants
      position the translational termination codon more than 50 nucleotides upstream of
      an exon-exon junction, creating a potential triggering signal for NMD in
      mammalian cells. Disruption of cellular NMD pathways by RNA interference-mediated
      knockdown of Upf1/Rent1 or Upf2/Rent2 or transfection of a dominant-negative Upf1
      mutant specifically enhanced expression of these two candidate NMD substrate
      mRNAs in cells, involving stabilization of each transcript. Ribonucleoprotein
      immunoprecipitation experiments revealed that both Upf1 and Upf2 can associate
      with an NMD-sensitive AUF1 mRNA 3'-UTR variant in cells. Finally, quantitation of
      AUF1 mRNA 3'-UTR splice variants during murine embryonic development showed that
      the expression of NMD-sensitive AUF1 mRNAs is specifically enhanced as
      development proceeds, contributing to dynamic changes in AUF1 3'-UTR structures
      during embryogenesis. Together, these studies provide the first evidence of
      linkage between the nonsense- and ARE-mediated mRNA decay pathways, which may
      constitute a new mechanism regulating the expression of ARE-containing mRNAs.

PMID- 17000772
TI  - Chromatin structure and transcription of the R1- and R2-inserted rRNA genes of
      Drosophila melanogaster.
AB  - About half of the rRNA gene units (rDNA units) of Drosophila melanogaster are
      inserted by the retrotransposable elements R1 and R2. Because transcripts to R1
      and R2 were difficult to detect on blots and electron microscopic observations of
      rRNA synthesis suggested that only uninserted rDNA units were transcribed, it has
      long been postulated that inserted rDNA units are in a repressed (inactive)
      chromatin structure. Studies described here suggest that inserted and uninserted
      units are equally accessible to DNase I and micrococcal nuclease and contain
      similar levels of histone H3 and H4 acetylation and H3K9 methylation. These
      studies have low sensitivity, because psoralen cross-linking suggested few
      (estimated <10%) of the rDNA units of any type are transcriptionally active.
      Nuclear run-on experiments revealed that R1-inserted and R2-inserted units are
      activated for transcription at about 1/5 and 1/10, respectively, the rate of
      uninserted units. Most transcription complexes of the inserted units terminate
      within the elements, thus explaining why previous molecular and electron
      microscopic methods indicated inserted units are seldom transcribed. The
      accumulating data suggest that all units within small regions of the rDNA loci
      are activated for transcription, with most control over R1 and R2 activity
      involving steps downstream of transcription initiation.

PMID- 17000773
TI  - Activation of alpha-tropomyosin exon 2 is regulated by the SR protein 9G8 and
      heterogeneous nuclear ribonucleoproteins H and F.
AB  - The inclusion of exons 2 and 3 of alpha-tropomyosin is governed through tissue
      specific alternative splicing. These exons are mutually exclusive, with exon 2
      included in smooth muscle cells and exon 3 included in nearly all other cell
      types. Several cis-acting sequences contribute to this splicing decision: the
      branchpoints and pyrimidine tracts upstream of both exons, UGC-repeat elements
      flanking exon 3, and a series of purine-rich enhancers in exon 2. Previous work
      showed that proteins rich in serine-arginine (SR) dipeptides act through the exon
      2 enhancers, but the specific proteins responsible for such activation remained
      unknown. Here we show that a 35-kDa member of the SR protein family, 9G8, can
      activate the splicing of alpha-tropomyosin exon 2. Using RNA affinity
      chromatography and cross-linking competition assays, we also demonstrate that the
      heterogeneous nuclear ribonucleoproteins (hnRNPs) H and F bind to and compete for
      the same elements. Overexpression of hnRNPs H and F blocked 9G8-mediated splicing
      both in vivo and in vitro, and small interfering RNA-directed depletion of H and
      F led to an increase in exon 2 splicing. These data suggest that the activation
      of exon 2 is dependent on the antagonistic activities of 9G8 and hnRNPs H and F.

PMID- 17000774
TI  - A novel cyclic AMP-dependent Epac-Rit signaling pathway contributes to PACAP38
      mediated neuronal differentiation.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP38) stimulation results
      in the activation of G(s)alpha protein-coupled receptors to regulate neuronal
      differentiation in a cyclic AMP (cAMP)-dependent manner. These pathways involve
      protein kinase A (PKA)-dependent processes, but a growing body of evidence
      indicates that cAMP also regulates cellular functions through PKA-independent
      signaling cascades. Here we show that the Rit small GTPase is regulated by
      PACAP38 in a cAMP-dependent but PKA-independent fashion. Rit activation results
      from stimulation of the cAMP-activated guanine nucleotide exchange factor Epac
      but does not appear to rely upon the activation of Rap GTPases, the accepted
      cellular Epac substrates. Although RNA interference studies demonstrated that
      Epac is required for PACAP38-mediated Rit activation, neither Epac1 nor Epac2
      activates Rit directly, indicating that Epac signals to Rit through a novel
      mechanism in which Rap signaling is not essential. Loss-of-function analysis
      demonstrated that Rit makes an important contribution to PACAP38-mediated
      neuronal differentiation. Surprisingly, although Rit is required for sustained
      extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein
      kinase signaling following nerve growth factor stimulation of pheochromocytoma 6
      (PC6) cells, Rit silencing selectively suppressed PACAP38-elicited activation of
      p38, without obvious effects on ERK signaling in the same cells. Moreover, the
      ability of PACAP38 to stimulate CREB-dependent transcription and to promote
      neurite outgrowth was inhibited by Rit knockdown. Together, these studies
      identify an unsuspected connection between cAMP and Rit signaling pathways and
      imply that Rit can function downstream of G(s)alpha/cAMP/Epac in a novel signal
      transduction pathway necessary for PACAP38-mediated neuronal differentiation and
      CREB signaling.

PMID- 17000775
TI  - An arc of unpaired "hinge bases" facilitates information exchange among
      functional centers of the ribosome.
AB  - Information must be shared and functions coordinated among the spatially distinct
      functional centers of the ribosome. To address these issues, a yeast-based
      genetic system enabling generation of stable strains expressing only mutant forms
      of rRNA was devised. The B1a bridge (helix 38) has been implicated in the subtle
      modulation of numerous ribosomal functions. Base-specific mutations were
      introduced into helix 38 at sites affecting the B1a bridge and where it contacts
      the aminoacyl-tRNA (aa-tRNA) D-loop. Both sets of mutants promoted increased
      affinities for aa-tRNA but had different effects in their responses to two A-site
      specific drugs and on suppression nonsense codons. Structural analyses revealed
      an arc of nucleotides in 25S rRNA that link the B1a bridge, the
      peptidyltransferase center, the GTPase-associated center, and the sarcin/ricin
      loop. We propose that a series of regularly spaced "hinge bases" provide fulcrums
      around which rigid helices can reorient themselves depending on the occupancy
      status of the A-site.

PMID- 17000776
TI  - Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing
      histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis.
AB  - The antiapoptotic transcription factor NF-kappaB is constitutively activated in
      many cancers and is important for cytokine-mediated progression and metastatic
      movement of tumors. Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis
      suppressor gene whose mechanisms of action are poorly understood. In this report,
      we demonstrate that BRMS1 decreases the transactivation potential of RelA/p65 and
      ameliorates the expression of NF-kappaB-regulated antiapoptotic gene products.
      BRMS1 immunoprecipitates with the RelA/p65 subunit of NF-kappaB with protein
      protein interactions occurring at the C terminus region of the rel homology
      domain but not at its known transactivation domains. Moreover, BRMS1 functions as
      a corepressor by promoting binding of HDAC1 to RelA/p65, where it deacetylates
      lysine K310 on RelA/p65, which suppresses RelA/p65 transcriptional activity.
      Selective small interfering RNA knockdown of BRMS1 confirms that chromatin-bound
      BRMS1 is required for deacetylation of RelA/p65, while enhancing chromatin
      occupancy of HDAC1 onto the NF-kappaB-regulated promoters cIAP2 and Bfl-1/A1. We
      observed in cells lacking BRMS1 a dramatic increase in cell viability after the
      loss of attachment from the extracellular matrix. Collectively, these results
      suggest that BRMS1 suppresses metastasis through its ability to function as a
      transcriptional corepressor of antiapoptotic genes regulated by NF-kappaB.

PMID- 17000777
TI  - APPL1 associates with TrkA and GIPC1 and is required for nerve growth factor
      mediated signal transduction.
AB  - The neurotrophin receptor TrkA plays critical roles in the nervous system by
      recruiting signaling molecules that activate pathways required for the growth and
      survival of neurons. Here, we report APPL1 as a TrkA-associated protein. APPL1
      and TrkA co-immunoprecipitated in sympathetic neurons. We have identified two
      routes through which this association can occur. APPL1 was isolated as a binding
      partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass
      spectrometry. The PDZ domain of GIPC1 directly engaged the C-terminal sequence of
      APPL1. This interaction provides a means through which APPL1 may be recruited to
      TrkA. In addition, the APPL1 PTB domain bound to TrkA, indicating that APPL1 may
      associate with TrkA independently of GIPC1. Isolation of endosomal fractions by
      high-resolution centrifugation determined that APPL1, GIPC1, and phosphorylated
      TrkA are enriched in the same fractions. Reduction of APPL1 or GIPC1 protein
      levels suppressed nerve growth factor (NGF)-dependent MEK, extracellular signal
      regulated kinase, and Akt activation and neurite outgrowth in PC12 cells.
      Together, these results indicate that GIPC1 and APPL1 play a role in TrkA
      function and suggest that a population of endosomes bearing a complex of APPL1,
      GIPC1, and activated TrkA may transmit NGF signals.

PMID- 17000778
TI  - The Bad guy cooperates with good cop p53: Bad is transcriptionally up-regulated
      by p53 and forms a Bad/p53 complex at the mitochondria to induce apoptosis.
AB  - Although the regulation of several Bcl-2 family molecules, including Puma, Noxa,
      Bax, and Bid, by p53 has been studied intensively, the interplay between Bad (Bcl
      2 antagonist of cell death) and p53 has not yet been reported thus far. Here, we
      report that p53 activates Bad transcription and expression through binding to a
      short conserved sequence located approximately 6.6 kb upstream of the translation
      start point. We also demonstrate that Bad physically interacts with cytoplasmic
      p53, thereby preventing p53 from entering the nucleus and resulting in reduced
      transcription of Bad. Moreover, Bad is able to direct p53 to the mitochondria and
      forms a p53/Bad complex at the mitochondria. Two lines of evidences support this
      hypothesis: first, when mitochondria purified from p53-deficient H1299 cells are
      incubated with p53 and either wild-type (wt) Bad or mutant Bad (this mutant binds
      p53 yet is unable to migrate to mitochondria), p53 can be detected only in
      mitochondria incubated with wt Bad and not in those incubated with mutant Bad;
      second, knockdown of Bad expression reduces mitochondrial localization of p53.
      The mitochondrial p53/Bad complex promotes apoptosis via activation and
      oligomerization of Bak. Elimination of Bad expression by RNA interference notably
      attenuates apoptosis induced by etoposide. Hence, our collective data provide the
      first evidence that Bad plays dual roles in both p53 transcription-dependent and 
      independent pathways.

PMID- 17000780
TI  - Renal outcome of neonatal renal venous thrombosis: review of 28 patients and
      effectiveness of fibrinolytics and heparin in 10 patients.
AB  - OBJECTIVES: Neonatal renal venous thrombosis is a rare disorder that can result
      in severe renal damage. To evaluate the experience over 10 years and review the
      effectiveness of fibrinolytic and/or heparin therapy, chart reviews were
      performed for newborns with renal venous thrombosis. PATIENTS, INTERVENTIONS, AND
      OUTCOME MEASURES: Twenty-eight newborns with renal venous thrombosis were treated
      at Children's Hospitals and Clinics of Minnesota and Fairview University Medical
      Center from 1991 to 2001. RESULTS: Unilateral involvement was noted in 25
      neonates (89%) and bilateral involvement in 3 (11%). Unilateral renal venous
      thrombosis affected mostly term infants, whereas 2 of 3 infants with bilateral
      renal venous thrombosis were <32 weeks' gestational age (birth weight: 745-1505
      g). One mother had antiphospholipid syndrome. Of 11 neonates evaluated for
      congenital thrombophilia, 1 had the factor V Leiden mutation. Ten neonates
      received either unfractionated or low molecular weight heparin for 3 days to 7
      months. Three infants with unilateral renal venous thrombosis treated with
      heparin alone did not seem to benefit from such therapy. Seven neonates were
      treated with fibrinolytics and unfractionated heparin (4 neonates with unilateral
      renal venous thrombosis and 3 with bilateral renal venous thrombosis). Treatment
      with fibrinolytics did not result in restoration of renal function in the 4
      neonates with unilateral renal venous thrombosis but was associated with return
      of almost normal function in the 2 neonates with bilateral renal venous
      thrombosis who received fibrinolytics immediately after renal venous thrombosis
      diagnosis. Two neonates treated with fibrinolytics suffered bleeding
      complications at the area of adrenal hemorrhage. Two neonates (not treated for
      renal venous thrombosis) died as a result of underlying disease. CONCLUSIONS:
      Most neonatal renal venous thrombosis is unilateral and does not respond to
      fibrinolytic therapy and heparin. The use of fibrinolytics may prevent chronic
      renal failure in neonates with bilateral renal venous thrombosis if begun within
      24 hours of diagnosis. Fibrinolytic therapy, however, is associated with a risk
      of bleeding, specifically if there is an associated adrenal hemorrhage.

PMID- 17000781
TI  - Shorter time to diagnosis and improved stage at presentation in Swiss patients
      with retinoblastoma treated from 1963 to 2004.
AB  - OBJECTIVES: Retinoblastoma is the most frequent intraocular malignancy in
      children. Early diagnosis is essential for globe salvage and patient survival.
      The aim of our study was to determine how time to diagnosis of retinoblastoma has
      evolved over a 40-year period in Switzerland. METHOD AND PATIENTS: A
      retrospective study of 139 Swiss patients with retinoblastoma was performed
      comparing 3 periods: (1) 1963-1983; (2) 1984-1993; and (3) 1994-2004. Factors
      taken into account were gender, laterality of retinoblastoma, age at first
      symptoms, type and first observer of symptoms, time to diagnosis, age at
      diagnosis, disease stage, and family history. RESULTS: Thirty-seven patients
      (26.6%) were treated in period 1, 44 (31.7%) in period 2, and 58 (41.7%) in
      period 3. Overall, the diagnostic interval decreased in a significant way from
      6.97 months in period 1 to 3.58 in period 2 and to 2.25 in period 3. When looking
      separately at unilateral and bilateral disease, the decrease of the diagnostic
      interval remained statistically significant in unilateral retinoblastoma; there
      was also a significant reduction in the number of patients with advanced group E
      disease (Murphree classification) (61.5% in period 1, 46.7% in period 2, 22.2% in
      period 3). In bilateral disease, the same observations were made to a lesser
      extent. However, there were no cases with group E disease in 10 patients with
      positive family history. Leukocoria (48.2%) and strabismus (20.1%) were the 2
      most frequent symptoms throughout the 3 periods. The only factors that
      statistically influenced the chances of having a diagnosis of group E disease
      were the diagnostic interval and period of diagnosis. CONCLUSIONS: Progress has
      been made in the diagnosis of retinoblastoma in Switzerland, notably in
      unilateral disease. Improvement to a lesser extent has also been observed in
      bilateral cases but without statistical significance. Greater effort is needed to
      teach physicians-in-training to recognize the importance of ocular symptoms and
      refer patients earlier.

PMID- 17000782
TI  - Management and outcomes of double aortic arch in 81 patients.
AB  - OBJECTIVES: Double aortic arch is a common form of complete vascular ring,
      encircling both the trachea and esophagus, resulting in noncardiac morbidity. We
      sought to describe management and outcomes in a large single institution clinical
      series. PATIENTS AND METHODS: We reviewed the medical charts of all of the
      patients diagnosed with double aortic arch at age <18 years. Data regarding
      clinical presentation, anatomy, management, and outcomes were abstracted.
      RESULTS: We identified 81 patients (67% males) born between 1964 and 2005 and
      presenting at a median age of 5 months (range: birth to 10.3 years). Respiratory
      symptoms were present in 91%, including stridor in 77%. Gastrointestinal symptoms
      were present in 40%, with choking with feeds being most common. The dominant
      branch of the double aortic arch was right in 72%. Associated cardiac anomalies
      were present in 18%, with noncardiac anomalies in 7%. Repair was performed in 79
      patients at a median age of 6 months. There were 2 deaths after surgical repair
      with no late deaths, with Kaplan-Meier survival estimates of 96% at 5 years.
      Postoperative complications included chylothorax in 9%. Only 1 patient required
      reoperation. The most common symptoms at most recent follow-up were respiratory
      (54%) followed by gastrointestinal symptoms (6%). Postoperative tracheal stenosis
      was documented in 14%, with tracheomalacia in 7%. There were no late reoperations
      and no evidence of aortic arch obstruction. CONCLUSIONS: Outcomes are excellent
      after repair of double aortic arch, although persistent respiratory symptoms are
      frequent and probably associated with previous compression-related maldevelopment
      of the trachea and major airways.

PMID- 17000779
TI  - Mediator modulates Gli3-dependent Sonic hedgehog signaling.
AB  - The physiological and pathological manifestations of Sonic hedgehog (Shh)
      signaling arise from the specification of unique transcriptional programs
      dependent upon key nuclear effectors of the Ci/Gli family of transcription
      factors. However, the underlying mechanism by which Gli proteins regulate target
      gene transcription in the nucleus remains poorly understood. Here, we identify
      and characterize a physical and functional interaction between Gli3 and the MED12
      subunit within the RNA polymerase II transcriptional Mediator. We show that Gli3
      binds to MED12 and intact Mediator both in vitro and in vivo through a Gli3
      transactivation domain (MBD; MED12/Mediator-binding domain) whose activity
      derives from concerted functional interactions with both Mediator and the histone
      acetyltransferase CBP. Analysis of MBD truncation mutants revealed an excellent
      correlation between the in vivo activation strength of an MBD derivative and its
      ability to bind MED12 and intact Mediator in vitro, indicative of a critical
      functional interaction between the Gli3 MBD and the MED12 interface in Mediator.
      Disruption of the Gli3-MED12 interaction through dominant-negative interference
      inhibited, while RNA interference-mediated MED12 depletion enhanced, both MBD
      transactivation function and Gli3 target gene induction in response to Shh
      signaling. We propose that activated Gli3 physically targets the MED12 interface
      within Mediator in order to functionally reverse Mediator-dependent suppression
      of Shh target gene transcription. These findings thus link MED12 to the
      modulation of Gli3-dependent Shh signaling and further implicate Mediator in a
      broad range of developmental and pathological processes driven by Shh signal
      transduction.

PMID- 17000783
TI  - Diffuse pneumocephalus in neonatal Citrobacter meningitis.
AB  - Pneumocephalus, intracranial air or gas collection, associated with neonatal
      meningitis is extremely rare. We report the first case in the United States and
      the second case in the world of intracranial gas accumulation in a neonate with
      Citrobacter koseri meningitis. The clinical presentation was acute with
      pneumocephalus demonstrated by cranial sonography and computed tomography. The
      clinical course was fatal despite the prompt administration of antibiotics.

PMID- 17000784
TI  - Severe hyperphosphatemia and hypocalcemic tetany after oral laxative
      administration in a 3-month-old infant.
AB  - A 3-month-old infant presented to the pediatric emergency department with
      respiratory distress and tetany after ingestion of a phosphate-containing oral
      laxative. The initial phosphorus level was 38.3 mg/dL. With aggressive fluid
      resuscitation and intravenous calcium administration, the infant completely
      recovered. Although the risks of phosphate-containing enemas are well described,
      life-threatening hyperphosphatemia can also result from administration of
      phosphate-containing oral laxatives. Aggressive fluid hydration is the mainstay
      of treatment. Intravenous calcium administration may be necessary to avoid
      hemodynamic collapse despite the theoretical possibility of metastatic
      calcifications. Physicians should be alerted to the possibility of phosphate
      toxicity and hypocalcemic tetany in young children when treated with over-the
      counter laxatives. Caregivers should be advised not to administer over-the
      counter laxatives to infants without physician supervision.

PMID- 17000785
TI  - The impact of gender on in-hospital mortality and morbidity after isolated aortic
      valve replacement.
AB  - The objective of our retrospective investigation was to examine the influence of
      gender on in-hospital mortality and morbidity after isolated aortic valve
      replacement (AVR). Between January 1993 and June 2002, 2212 patients (782
      females, 1430 males) underwent AVR. Propensity matching was used to adjust for
      numerous differences in baseline characteristics and perioperative variables
      between groups. Unadjusted in-hospital mortality was higher in females (27 [3.5%]
      females versus 23 [1.6%] males; P = 0.005). An analysis using 1:1 matching by
      propensity score did not find a significant difference in in-hospital mortality
      [OR (95% confidence intervals), 1.0 [0.4, 2.6]; P = 0.99) or overall morbidity
      (1.4 [0.7, 2.5]; P = 0.29) between groups. Further analyses, including
      classification of women and men into quintile groups by propensity scores and
      logistic regression models with propensity score adjustment, found that females
      were at increased risk for cardiac morbidity [OR (95% CI), 3.4 [1.1, 10.8]; P =
      0.038), but not mortality (0.9 [0.3, 2.5]; P = 0.88) nor other morbidities. These
      results suggest that there is no greater than a 2.5-fold increase in risk for
      females compared with males undergoing AVR. Female gender, however, may impart
      increased risk for cardiac morbidity after AVR.

PMID- 17000786
TI  - Clonidine attenuated early proinflammatory response in T-cell subsets after
      cardiac surgery.
AB  - T-cells play a central role in the immune response to injury. Cardiac surgery is
      associated with significant risk of systemic inflammatory response syndrome and
      subsequent unbalanced induction of proinflammatory cytokines. As clonidine has
      immunomodulating properties via reducing sympathetic activity, this study
      involved the analysis of T-cell function in the early postoperative period in
      patients undergoing coronary artery bypass graft surgery. Forty patients
      undergoing cardiac surgery were randomly allocated to one of the following
      groups: clonidine group (n = 20) [clonidine 1 microg kg(-1) h(-1)] and placebo
      group (n = 20). Study medication was started after induction of anesthesia and
      maintained until 6 h after surgery. Blood samples to determine Th1 and Th2 cells
      and cytotoxic lymphocytes (Tc1 and Tc2 cells) were drawn preoperatively, on
      admission to the intensive care unit, 6 and 12 h postoperatively as well as on
      the morning of days 1 and 2 after surgery. In the clonidine group significantly
      lower levels of Th1/Th2 ratios as well as Tc1/Tc2 ratios were found 6 h
      postoperatively compared to the placebo group (P < 0.05). Clonidine changed the
      ratio of T-lymphocyte subpopulations in peripheral blood in favor of a
      proinflammatory response, which might be favorable for maintaining immune balance
      after surgery.

PMID- 17000787
TI  - Pharmacologic evidence for the involvement of central and peripheral opioid
      receptors in the cardioprotective effects of fentanyl.
AB  - BACKGROUND: We investigated the involvement of central and peripheral opioid
      receptors (OR) in the cardioprotective effects of fentanyl (FENT) in a model of
      myocardial ischemia/reperfusion injury associated with pharmacologically induced
      sympathetic overactivity in anesthetized rabbits. METHODS: Central sympathetic
      stimulation was achieved through intracerebroventricular injection of l-glutamate
      in animals submitted to 35 min of coronary occlusion followed by 120 min of
      reperfusion. Rabbits received naloxone HCl intracerebroventricularly or naloxone
      methiodide IV, a quaternary compound that does not cross the blood-brain barrier,
      5 min before FENT treatment (5 or 50 microg/kg, IV). RESULTS: Infarct area was
      reduced only by FENT 50 (from 51% +/- 2% to 24% +/- 2%). This protective effect
      was abolished by peripheral (42% +/- 4%), but not central, OR blockade (32% +/-
      3%). The number of premature ventricular complexes during the ischemic period (54
      +/- 3) was reduced by FENT 50 (19 +/- 7), an effect blunted by central (40 +/- 3)
      but not peripheral (18 +/- 7) blockade of OR. During reperfusion, the number of
      premature ventricular complexes (134 +/- 50) was reduced to 9 +/- 5 by FENT 50
      and was prevented by central (42 +/- 4) as well as peripheral (20 +/- 11) OR
      blockade. The mortality rate (50%) and incidence of ventricular tachycardia (55%)
      were completely abolished by FENT 50. CONCLUSIONS: We conclude that fentanyl's
      effects for limiting myocardial ischemic injury are mediated via peripheral ORs
      while opioid's antiarrhythmic actions are mediated via central OR agonism.

PMID- 17000789
TI  - A comparison of fenoldopam with dopamine and sodium nitroprusside in patients
      undergoing cross-clamping of the abdominal aorta.
AB  - Fenoldopam, a selective dopamine-1-receptor agonist, decreases arterial blood
      pressure rapidly, with a brief duration of action similar to sodium nitroprusside
      (SNP), but in contrast to SNP, it increases renal blood flow. We compared the
      hemodynamic and renal effects of fenoldopam in patients undergoing abdominal
      aortic surgery requiring cross-clamping of the aorta with another therapeutic
      option, dopamine and SNP. Fenoldopam or 2 mcg x kg(-1) x min(-1) of dopamine and
      SNP was infused before incision in 60 randomly selected patients in a double
      blind fashion. Hemodynamic variables were recorded before incision, immediately
      before clamping the aorta, 5 min after cross-clamp release and upon completion of
      surgery. Urine output, serum creatinine, and creatinine clearance were measured
      intraoperatively and postoperatively. Characteristics were compared between
      groups using two-sample rank sum test for continuous variables and Fisher's exact
      test for discrete variables. The occurrence of severe hypotension, maximum
      systolic blood pressure, and need for additional antihypertensive drugs were not
      different between the groups. Most intraoperative hemodynamic variables and all
      indices of renal function did not differ according to treatment. Therefore,
      fenoldopam has no therapeutic advantage compared with similar therapies in
      patients undergoing major vascular surgery involving cross-clamping of the aorta.

PMID- 17000788
TI  - Kappa-opioid receptor antagonism improves recovery from myocardial stunning in
      chronically instrumented dogs.
AB  - We tested the hypothesis that the selective kappa-opioid receptor antagonist nor
      binaltorphimine (nor-BNI) improves recovery from myocardial stunning. Ten dogs
      were chronically instrumented for measurement of heart rate, left atrial, aortic
      and left ventricular pressure (LVP), and the maximum rate of LVP increase (LV
      dP/dt(max)) and decrease (LV dP/dt(max)), coronary blood flow velocity and
      myocardial wall-thickening fraction. Regional myocardial blood flow was
      determined with fluorescent microspheres. Catecholamine plasma levels were
      measured by high-performance liquid chromatography, and beta-endorphin and
      dynorphin plasma levels by radioimmunoassay. An occluder around the left anterior
      descending artery (LAD) allowed induction of a reversible LAD-ischemia. Animals
      underwent two experiments in a randomized crossover fashion on separate days: (a)
      10 min LAD-occlusion (control experiment), (b) second ischemic episode 24 h after
      nor-BNI (2.5 mg/kg IV) (intervention). Dogs receiving nor-BNI showed an increase
      in wall-thickening fraction, LV dP/dt(max) and LV dP/dt(min) before ischemia and
      during the whole reperfusion (P < 0.05 versus control experiment). After nor-BNI
      pretreatment, dynorphin levels increased after induction of ischemia to a peak
      level of 15.1 +/- 3.6 pg/mL (P < 0.05 versus control experiment). The increase in
      plasma beta-endorphin during ischemia and early reperfusion was attenuated after
      nor-BNI. Compared with the control experiment, nor-BNI left global hemodynamics,
      regional myocardial blood flow, and catecholamine levels unchanged. In
      conclusion, nor-BNI improves recovery from myocardial stunning after regional
      myocardial ischemia in chronically instrumented dogs.

PMID- 17000790
TI  - The impact of tissue factor pathway inhibitor on coagulation kinetics determined
      by thrombelastography.
AB  - BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a 40-kDa, endogenous
      protein that inhibits tissue factor (TF)-initiated coagulation by bonding with
      activated factor X (FXa). The TFPI/FXa complex then subsequently binds with
      TF/activated factor VII (FVIIa) complex, ultimately inhibiting thrombin
      generation. Heparin administration causes endothelial release of TFPI
      concentrations up to sixfold normal values. Thrombelastography (TEG) is often
      used to monitor hemostasis in the perioperative period, and TFPI could
      potentially affect the diagnostic interpretation of TEG-based data, given its
      inhibition of both common and TF coagulation pathways. Thus, in this study we
      characterized the effect of TFPI on coagulation kinetics via TEG. METHODS: Whole
      blood, Factor VII-deficient plasma, and normal plasma were exposed in vitro to
      various concentrations of TFPI, after which unmodified, celite-activated, and TF
      activated TEG were performed. RESULTS: The addition of 87.5 ng/mL TFPI (twice
      normal concentration) was required to prolong clot propagation in whole blood,
      with propagation and strength only significantly affected by the addition of 175
      ng/mL concentrations. Experiments with Factor VII-deficient plasma demonstrated
      that TFPI-mediated suppression of coagulation kinetics at these concentrations
      was secondary to FXa inhibition. Celite activation markedly attenuated TFPI
      mediated effects on coagulation kinetics, whereas TF activation accentuated TFPI
      mediated prolongation of clot initiation and diminution of propagation.
      CONCLUSIONS: In settings involving heparin administration (e.g., cardiopulmonary
      bypass), TFPI-mediated inhibition of coagulation should be considered during TEG
      based hemostatic monitoring.

PMID- 17000791
TI  - Modeling ischemia-induced dyssynchronous myocardial contraction.
AB  - Left ventricular (LV) contraction dyssynchrony is not easily quantified. We
      previously described a model for quantifying LV dyssynchrony that referenced
      regional amplitude and phase angles to global LV systole using esmolol-induced
      regional dyskinesis. We tested the hypothesis that our sine wave model and phase
      angle analysis of regional dyssynchrony in a canine model could also assess
      dyssynchrony of contraction during regional ischemia. Hence we compared
      intracoronary esmolol and matched regional ischemia in 10 anesthetized open-chest
      dogs. Regional and total LV volumes (conductance catheter), piezoelectric crystal
      shortening, and LV pressures were measured before, during, and after esmolol
      induced apical dyskinesis and matched regional ischemia. We defined regional
      phase angle of contraction (alpha) as the relative distance, measured in degrees,
      that regional minimal volume differed from global end-systole. We also compared
      maximal stroke volume (SV), observed effective SV (that portion of regional SV
      contributing to total SV for each treatment), and calculated effective SV (total
      regional SV x cosine alpha). Dobutamine infusion increased homogeneity of
      regional alpha relative to baseline. Both esmolol and ischemia significantly
      delayed (P < 0.05) apical contraction as quantified by increased alpha (12.4
      degrees +/- 28.1 degrees to 27.4 degrees +/- 30.4 degrees and 54.2 degrees +/-
      32.6 degrees , respectively) (mean +/- sd) and decreased regional effective SV
      (4.7 +/- 2.5 mL to 3.6 +/- 2.2 mL and 4 +/- 2.5 mL, respectively) relative to
      baseline. Our study indicates that intracoronary esmolol and ischemia induced
      qualitatively similar mechanical effects on myocardial function and that a sine
      wave model to estimate regional effective SV is a sensitive method to detect and
      quantify regional dyssynchrony induced by ischemia. Potentially, phase angle and
      regional amplitude analyses may prove to be effective measures to identify and
      quantify the beneficial effects of resynchronization therapies on myocardial
      function.

PMID- 17000792
TI  - An unusual echodensity in the ascending aorta: transesophageal echocardiographic
      visualization of a protruding coronary stent.

PMID- 17000793
TI  - Laparoscopic surgery in a patient with Fontan physiology.
AB  - Laparoscopic surgery represents a significant advance in surgical technique, but
      a number of physiologic sequelae result from positioning and insufflation. These
      physiologic changes may be more significant in patients with complex congenital
      heart disease. We present the anesthetic management of a patient with Fontan
      physiology who successfully underwent two separate laparoscopic procedures.

PMID- 17000794
TI  - Don't confuse the anesthetic with the anesthesiologist!

PMID- 17000795
TI  - Sedation and anesthesia protocols used for magnetic resonance imaging studies in
      infants: provider and pharmacologic considerations.
AB  - Most studies report the efficacy of only a single drug to achieve sedation in a
      broad age range of children. In clinical practice, a variety of sedative and
      anesthetic regimes are monitored by nurses and physicians. In this study we
      report the efficacy of a tiered approach to monitoring and sedation in infants.
      Two-hundred-fifty-eight infants who required magnetic resonance imaging (MRI)
      studies received either oral chloral hydrate (n = 102) or bolus doses of IV
      pentobarbital (n = 67) monitored by nurses or IV propofol infusion (n = 68)
      titrated by physicians. Fewer cardiorespiratory events were observed in the
      chloral hydrate group (2.9%) compared to pentobarbital (13.4%) and propofol
      groups (13.6%); P < 0.05, propofol versus chloral hydrate. Infants who received
      propofol were ready to begin MRI scanning earlier (mean 9.1 +/- 6.7 min) than
      infants who received oral chloral hydrate (mean 23.5 +/- 13.4 min; P < 0.05). The
      time to discharge was longest in the pentobarbital (mean 80.3 +/- 39.2 min) and
      shortest in the propofol group (mean 53.9 +/- 30.1 min; P < 0.05). Infants in the
      chloral hydrate group moved more frequently (22.5%) during MRI scanning (with
      four sedation failures of 102) compared to 12.2% in the pentobarbital group and
      1.4% in the propofol group (P < 0.001).

PMID- 17000796
TI  - The incidence and risk factors for hypotension during emergent decompressive
      craniotomy in children with traumatic brain injury.
AB  - We conducted a retrospective cohort study in children <13 yr with traumatic brain
      injury (TBI) at a Level 1 pediatric trauma center to describe risk factors for
      intraoperative hypotension (IH) during emergent decompressive craniotomy. Between
      1994 and 2004, 108 children underwent emergent decompressive craniotomy for TBI.
      Overall, 56 (52%) patients had IH. Independent risk factors for IH were each 10
      mL estimated blood loss/kg (ARR 1.15 95% CI 1.08-1.22), each mm of computed
      tomography (CT) midline shift (ARR 1.04 95%CI 1.01-1.07), each 10 mL of CT lesion
      volume (ARR 1.03 95%CI 1.01-1.05), and emergency department (ED) hypotension (5/5
      patients with ED hypotension had IH). CT midline shift > or =4 mm predicted IH
      (ARR 1.67 95% CI 1.06-2.63), independent of blood loss. IH occurred frequently
      during emergent decompressive craniotomy in children with TBI. ED hypotension,
      blood loss, CT lesion volume, and CT midline shift predicted IH.
      Anesthesiologists can expect children with preoperative CT midline shift > or =4
      mm to have IH during this procedure.

PMID- 17000797
TI  - Epidural lidocaine induces dose-dependent neurologic injury in rats.
AB  - Although epidural lidocaine administered as a bolus has been shown to cause
      little neurotoxicity, local anesthetics are often administered repetitively or
      continuously into the epidural space, and in high doses may induce neurologic
      injury. We investigated whether epidural lidocaine is neurotoxic when a large
      dose is continuously administered in rats, and whether the functional impairment
      and histologic damage is dose dependent. In Experiment 1, 13 rats received a 120
      min epidural infusion (at 5 microL/min) of saline or 2% lidocaine. Four days
      after infusion, rats given 2% lidocaine developed significantly more prolonged
      tail-flick latencies and showed more apparent morphologic damage than those given
      saline. In Experiment 2, 41 rats were randomly divided into 5 groups to receive
      an epidural infusion of saline for 120 min or 5% lidocaine for 15, 30, 60, or 120
      min at a rate of 5 muL/min. Rats given 5% lidocaine for 120 min developed a
      significant increase in tail-flick latency. Paw pressure thresholds did not
      change in any group. Nerve injury scores for rats given 5% lidocaine for 30, 60,
      and 120 min were significantly higher than those for rats given saline.
      Significant difference in damage in nerve roots was also observed among rats
      given the anesthetic for different durations of time; nerve injury scores with
      120-min infusion were higher than with 15- and 30-min infusions, and injury with
      60-min infusion was greater than with 15-min infusion. In conclusion, these
      results suggest that epidural lidocaine causes dose-dependent neurotoxicity after
      continuous infusion in rats.

PMID- 17000798
TI  - Anesthetic properties of a propofol microemulsion in dogs.
AB  - Microemulsions of propofol with nanometer droplet diameter are alternatives to
      soybean macroemulsions for inducing anesthesia, and may have important
      advantages. We used a propofol (10 mg/mL) microemulsion (particle diameter 24.5
      +/- 0.5 nm) and a commercial macroemulsion to induce anesthesia in dogs (n = 10)
      using a randomized, crossover design separated by a 7-day rest interval. The end
      points were loss of leg withdrawal after a toe pinch and changes in vital signs.
      Venous blood samples were acquired at multiple times to measure plasma propofol
      concentrations and indices of erythrocytes, leukocytes, and coagulation. All dogs
      were rendered insensitive to pain followed by successful recovery without
      noticeable complications. Comparing indices between microemulsion and
      macroemulsion formulations, no differences were noted with respect to dose (10.3
      +/- 1.2 and 9.7 +/- 1.6 mg/kg, respectively, P = 0.39), time to induction (1.0 +/
      0.1 and 1.0 +/- 0.2 min, P = 0.39), time to recovery (17.4 +/- 4.6 and 18.2 +/-
      3.8 min, P = 0.70), heart rate (P = 0.62), arterial blood pressure (P = 0.81),
      respiratory rate (P = 0.60), hemogram variables, prothrombin time (P = 0.89),
      activated partial thromboplastin time (P = 0.76), fibrinogen concentration (P =
      0.52), platelet concentration (P = 0.55), or plasma propofol concentrations (P =
      0.20). Induction with a propofol microemulsion or macroemulsion did not
      significantly vary with respect to vital signs, the hemogram, clotting variables,
      and plasma propofol concentrations.

PMID- 17000799
TI  - Model-based detection of endobronchial intubation.
AB  - To detect endobronchial intubation (EBI) noninvasively in real time, we developed
      a novel, automated, lumped model-based approach. The model uses routinely
      monitored airway pressure and flow as inputs. The specificity of the method in
      detecting EBI was determined by testing events of stiff chest wall (SCW) in the
      absence of EBI. EBI was induced in 10 anesthetized, paralyzed, and mechanically
      ventilated mongrel dogs (19-45 kg) by advancing the endotracheal tube into the
      right mainstem bronchus. The event of SCW was created by wrapping a pressure cuff
      around the chest. Airway pressure and flow were continuously recorded at the
      mouth, and respiratory impedance was estimated from these signals. Model
      parameters were iteratively identified until the root mean square error between
      the respiratory and model-predicted impedance was minimum. The change in model
      parameters during EBI from baseline was analyzed. In nine of 10 cases, it was
      determined that during EBI, the model's compliance element (C1) decreased > or
      =50% and model's resistance element (R2) changed < or =10-fold from baseline.
      Testing this rule on 40 cases of SCW, four false positives were obtained. During
      SCW, R1 and R2 increased, whereas C2 decreased significantly from baseline. This
      preliminary study is a promising step toward noninvasive, real-time detection of
      EBI to aid clinicians in decision making.

PMID- 17000800
TI  - The discriminant power of simultaneous monitoring of spontaneous
      electroencephalogram and evoked potentials as a predictor of different clinical
      states of general anesthesia.
AB  - Spontaneous or evoked electrical brain activity is increasingly used to monitor
      general anesthesia. Previous studies investigated the variables from spontaneous
      electroencephalogram (EEG), acoustic (AEP), or somatosensory evoked potentials
      (SSEP). But, by monitoring them separately, the available information from
      simultaneous gathering could be missed. We investigated whether the combination
      of simultaneous information from EEG, AEP, and SSEP shows a more discriminant
      power to differentiate between anesthesia states than from information derived
      from each measurement alone. Therefore, we assessed changes of 30 EEG, 21 SSEP,
      and 29 AEP variables recorded from 59 patients during four clinical states of
      general anesthesia: "awake," "light anesthesia," "surgical anesthesia," and "deep
      surgical anesthesia." The single and combined discriminant powers of EEG, AEP,
      and SSEP variables as predictors of these states were investigated by
      discriminant analysis. EEG variables showed a higher discriminant power than AEP
      or SSEP variables: 85%, 46%, and 32% correctly classified cases, respectively.
      The frequency of correctly classified cases increased to 90% and 91% with
      information from EEG + AEP and EEG + AEP + SSEP, respectively. Thus, future
      anesthesia monitoring should consider combined information simultaneously
      distributed on different electrophysiological measurements, rather than single
      variables or their combination from EEG or AEP or SSEP.

PMID- 17000801
TI  - The contribution of remifentanil to middle latency auditory evoked potentials
      during induction of propofol anesthesia.
AB  - There is a debate regarding whether opioids, as a component of general
      anesthesia, are adequately reflected in the assessment of anesthesia based on
      derivatives of the electroencephalogram. To test the hypothesis of a possible
      quantitative contribution of remifentanil on middle latency auditory evoked
      potentials, we studied its interaction with propofol anesthesia in 45
      unpremedicated male patients undergoing elective lower limb orthopedic surgery.
      They were allocated randomly to three groups. The first two groups received
      remifentanil either with a high (8 ng mL(-1)) or a low (3 ng mL(-1) target
      concentration using target-controlled infusion (TCI). The third group received
      spinal anesthesia instead of remifentanil. Anesthesia was induced by a stepwise
      increase in propofol concentration using TCI. The auditory evoked potential index
      (AEPex) and calculated propofol effect site concentrations were determined at
      loss of consciousness and the reaction to laryngeal mask airway insertion was
      noted. The propofol infusion was then converted to a closed-loop TCI using an
      AEPex value of 40 as the target. We found no significant contribution of
      remifentanil alone on the auditory evoked response, whereas increasing
      concentrations of remifentanil led to a significant decrease of the calculated
      propofol effect site concentrations (P = 0.023) necessary for unconsciousness.
      Prediction probability for AEPex was inversely related to the remifentanil
      concentration and was best for the control group, which received propofol alone.
      These results support previous findings of a quantitative interaction between
      remifentanil and propofol for loss of consciousness but question the specific
      contribution of remifentanil to auditory evoked potentials.

PMID- 17000802
TI  - An anesthesia information system designed to provide physician-specific feedback
      improves timely administration of prophylactic antibiotics.
AB  - Surgical site infections are a frequent cause of morbidity and mortality and add
      significantly to the cost of care. One component of the national Surgical
      Infection Prevention (SIP) program is to ensure timely administration of
      prophylactic antibiotics, a key factor to reduce postoperative infection. Our
      anesthesia department decided to assume the responsibility for timing and
      administration of antibiotic prophylaxis and we initiated a multitiered approach
      to remind the anesthesiologist to administer the prophylactic antibiotics. We
      used our anesthesia clinical information system to implement practice guidelines
      for timely antibiotic administration and to generate reports from the database to
      provide specific feedback to individual care providers with the goal of ensuring
      that patients receive antibiotic prophylaxis within 1 h of incision. Before the
      initiation of this project, 69% of eligible patients received antibiotics within
      60 min of the incision. After the program began, there was a steady increase in
      compliance to 92% 1 yr later. Provider-specific feedback increases compliance
      with practice guidelines related to timely administration of prophylactic
      antibiotics. Anesthesia information systems hold promise for implementing and
      monitoring new practice guidelines and the anesthesiologist may play a key role
      in influencing surgical outcomes by ensuring appropriate therapy that may not be
      directly related to anesthesia care.

PMID- 17000803
TI  - A computer evaluation of ventilation performance in a negative-pressure operating
      theater.
AB  - BACKGROUND: A negative-pressure operating theater is required to limit the spread
      of respiratory diseases in patients with severe acute respiratory syndrome,
      tuberculosis, avian influenza, or similar infectious diseases. In Hong Kong, we
      converted a conventional operating theater into a negative-pressure operating
      theater that has been in service for more than a year. In this article, we
      introduce its ventilation design and evaluate the airflow performance in relation
      to different combinations of medical lamp configurations and modes of launching
      infectious particles into the room air. METHODS: We used a computational fluid
      dynamics technique for the numerical analysis. RESULTS: Our analyses showed that
      the airflow performance in the negative-pressure operating theater was
      satisfactory and comparable to the original positive-pressure design. The airflow
      pattern effectively controlled the dispersion of infectious particles. Our
      calculations demonstrated that the airflow contained the dispersion of infectious
      particles released from the patient sufficiently to protect the surgical team,
      and vice versa. CONCLUSIONS: Computational fluid dynamics can be used to assess
      airflow in a negative-pressure operating room and model the dispersion of
      infectious particles from the patient.

PMID- 17000804
TI  - Economic, educational, and policy perspectives on the preincision operating room
      period.

PMID- 17000805
TI  - Task analysis of the preincision surgical period: an independent observer-based
      study of 1558 cases.
AB  - Intense production pressure has focused on the preincision period (from patient
      on-table to incision) as an important component of overall operating room
      efficiency. We conducted a prospective study in which trained independent
      observers measured the performance of anesthesiologists, surgeons, and nursing
      staff to determine anesthesia release time (ART, patient-on-table until release
      for surgical preparation) and surgical preparation time (SPT, start surgical
      preparation to incision) and the factors, including delays, that affect their
      duration. We enrolled 1558 patients undergoing elective surgery in a tertiary
      medical center. The mean ART was 21 +/- 16 min. Mean SPT was 22 +/- 13 min, and
      mean case length was 207 +/- 123 min. Significant variation was seen in both ART
      (range, 1-115 min) and SPT (range, 1-130 min). Multivariate regression analysis
      revealed ASA physical status, age, level of resident training, invasive
      monitoring, case length, and case number in the room were all positive predictors
      of ART duration (P < 0.05). In contrast, gender, body mass index, number of
      anesthesia personnel concurrently in the room, and number of rooms covered per
      anesthesia attending were not predictors for ART (P > 0.05). Delays affected both
      ART and SPT and were encountered in 24.5% of all procedures (surgery 66.8%,
      anesthesiology 21.7%, and logistical 11.5%). For operating room scheduling
      purposes, we conclude that assigning a constant fixed duration for anesthetic
      induction is inappropriate and will result in creating erroneous administrative
      expectations.

PMID- 17000806
TI  - Task analysis of the preincision period in a pediatric operating suite: an
      independent observer-based study of 656 cases.
AB  - We designed this cross-sectional investigation to assess anesthesia release time
      (ART = patient-on-table until release for surgical preparation) and surgical
      preparation time (start of surgical preparation to incision) of children
      undergoing anesthesia and surgery (n = 656). Data collected by trained
      independent observers included variables such as age, ASA physical status,
      anesthetic technique, and placement of invasive monitoring. We found that mean
      ART was 11.0 +/- 9.7 min and the mean surgical preparation time was 11.1 +/- 10.0
      min. Also, ART ranged from 7 +/- 7 min (for mask anesthesia) to 52 +/- 18 min
      (general anesthesia/endotracheal tube and invasive hemodynamic monitoring). The
      percentage of ART of the total case length was 15% +/- 7%, with a wide
      variability depending on the total case length. We also found that there is a
      significant variability in ART as a function of the surgical service involved
      (analysis of variance; P = 0.0001), ASA physical status (P = 0.0001), and age.
      For example, younger children had a significantly longer ART as compared with
      older children (P = 0.001). Room coverage ratio by the attending anesthesiologist
      and training level of the anesthesia resident did not impact ART (P = not
      significant). We conclude that ART in children undergoing surgery is highly
      variable and is a function of factors such as the surgical service involved, age
      of the child, and ASA physical status of the child. These factors should be
      considered when scheduling a surgical case.

PMID- 17000807
TI  - Resident teaching versus the operating room schedule: an independent observer
      based study of 1558 cases.
AB  - Efforts to improve operating room efficiency may threaten clinician training.
      Therefore, we designed a prospective, observational study to determine the actual
      time spent teaching anesthesiology residents during the interval from patient-on
      table to skin incision and to determine whether anesthesia teaching in the peri
      induction period increases the time to surgical incision. This study was
      conducted in an inpatient operating room suite of a tertiary academic medical
      center. Of 1558 cases examined, 75% had an element of teaching (mean percent
      teaching per case = 46.4). A 33% decrease in teaching occurs when the attending
      anesthesiologist concurrently directed care in 2 rooms (P < 0.001). The percent
      teaching significantly increased as a function of ASA physical status
      classification and time of day of surgical case (P = 0.001). Teaching accounted
      for a mean increase of time to incision of 4.5 +/- 3.2 min, but represented only
      3% of the mean surgical case length (207 +/- 132 min). We conclude that teaching
      occurs in the majority of cases in the operating room and although it contributes
      to increased time to incision, this increase is insignificant compared with the
      time required to complete the surgical procedure.

PMID- 17000808
TI  - Can the attending anesthesiologist accurately predict the duration of anesthesia
      induction?
AB  - In a prospective, observational study, the attending anesthesiologists'
      prediction of anesthesia release time (ART) of the patient to the surgical team
      was highly correlated with actual ART (r = 0.77; P < or = 0.001). However, this
      was true only in the aggregate (n = 1265 patients). Indeed, offsetting degrees of
      under- and over-predicting (24% each) reduced accuracy to only 53% per individual
      case. For example, under-prediction was associated with ASA physical status IV, a
      regional anesthetic technique, age >65 yr, and the use of invasive hemodynamic
      monitoring (P = 0.006). In fact, as the degree of case difficulty increased, the
      correlation coefficient between predicted and actual ART decreased, indicating a
      poor predictive value with more difficult inductions (r = 0.82 to r = 0.44; P <
      or = 0.004). We conclude that knowledge of the presence of specific factors that
      lead to inaccurate predictions of time required for induction of anesthesia may
      enhance the accuracy of the operating room schedule.

PMID- 17000809
TI  - The incidence and outcome of perioperative pulmonary aspiration in a university
      hospital: a 4-year retrospective analysis.
AB  - We evaluated the current incidence and outcome of perioperative pulmonary
      aspiration (PPA) in the nonobstetric adult population at a tertiary university
      medical center. A 4-yr retrospective analysis (January 2001-December 2004) was
      conducted using both quality improvement data and the hospital-wide medical
      archive recording system. PPA was defined as either detection of nonrespiratory
      secretions from the tracheobronchial tree or development of new pulmonary
      symptoms and/or new abnormalities in chest radiographs within 24 hr
      postoperatively. Of 99,441 anesthetics, 14 cases had confirmed PPA. Seven of them
      (50%) occurred in connection with gastroesophageal procedures. All patients had
      one or more predisposing risk factors for PPA. PPA occurred under general
      anesthesia in 10 patients and under monitored anesthesia care in 4 patients. In
      general anesthesia cases, the aspiration was recognized immediately after
      induction in 5 patients and occurred during changing of the endotracheal tubes in
      5. The PPA was detected during the surgical procedures in all the monitored
      anesthesia care cases. Six patients with confirmed PPA developed pulmonary
      complications, of which, one died. Ten of 14 (70%) cases of PPA were the result
      of improper anesthesia technique. The current incidence of PPA is 1 of 7103, with
      morbidity 1 of 16,573 and mortality 1 of 99,441.

PMID- 17000810
TI  - Cerebral metabolism assessed with microdialysis in uncontrolled hemorrhagic shock
      after penetrating liver trauma.
AB  - In a porcine model of uncontrolled hemorrhagic shock, we evaluated the effects of
      fluid resuscitation versus arginine vasopressin (AVP) combined with hypertonic
      hyperoncotic hydroxyethyl starch solution (HHS) on cerebral perfusion pressure
      (CPP) and on cerebral metabolism using intracerebral microdialysis. Sixteen
      anesthetized pigs were subjected to uncontrolled liver bleeding until hemodynamic
      decompensation, followed by resuscitation using either fluid (n = 8) or AVP/HHS
      (n = 8). Thirty minutes after drug administration, bleeding was controlled by
      manual compression, and colloid and crystalloid solutions were administered in
      both groups. All surviving animals were observed for one hour. After hemodynamic
      decompensation, fluid resuscitation resulted in a smaller increase of CPP than
      did AVP/HHS (mean +/- sem; 24 +/- 5 vs 45 +/- 7 mm Hg; P < 0.01). Mean (+/- sem)
      cerebral venous partial pressure of oxygen was significantly decreased (P < 0.01)
      5 min after fluid compared with 5 min after AVP/HHS administration (36 +/- 3 vs
      64 +/- 4 torr). Cerebral metabolism was comparable in both groups. In conclusion,
      AVP/HHS proved to be superior to fluid in the initial phase of therapy with
      respect to CPP and cerebral oxygenation, but was comparable to fluid regarding
      cerebral metabolism and secondary cell damage in surviving animals.

PMID- 17000811
TI  - Dexmedetomidine does not increase the incidence of intracarotid shunting in
      patients undergoing awake carotid endarterectomy.
AB  - Systemic administration of dexmedetomidine (DEX) decreases cerebral bloodflow
      (CBF) via direct alpha-2-mediated constriction of cerebral blood vessels and
      indirectly via its effect on the intrinsic neural pathway modulating vascular
      smooth muscle. Reduction in CBF without a concomitant decrease in cerebral
      metabolic rate has raised concerns that DEX may limit adequate cerebral
      oxygenation of brain tissue in patients with already compromised cerebral
      circulation (e.g., carotid endarterectomy [CEA]). In this study, we established
      the incidence of intraarterial shunting used as a sign of inadequate oxygen
      delivery in a consecutive series of 123 awake CEA performed in our institution
      using DEX as a primary sedative. Data were prospectively recorded in 151 patients
      who underwent CEA during the study period. Eighteen patients were sedated with
      midazolam and fentanyl (M/F) for medical or logistical reasons. Patients thought
      to be at risk of an intraoperative stroke were treated with a prophylactic
      intraarterial shunt. These patients, as well as those who required general
      anesthesia, were excluded from the final analysis. Five patients (4.3%) in the
      DEX group required intraarterial shunts. The incidence of shunting in patient
      undergoing awake CEA in our institution is 10% (historical control). No patients
      developed a stroke or other serious complications. It appears that the use of DEX
      as a primary sedative drug for CEA does not increase the incidence of
      intraarterial shunts.

PMID- 17000812
TI  - Suprasternal Doppler estimation of cardiac output: standard versus sequential
      combined spinal epidural anesthesia for cesarean delivery.
AB  - BACKGROUND: Sequential (Seq) combined spinal epidural (CSE) may provide better
      cardiovascular stability than standard (Std) CSE for cesarean delivery. We
      compared the cardiovascular stability of both techniques using suprasternal
      Doppler. METHODS: Healthy women (n = 40) scheduled for elective cesarean delivery
      were randomized into two groups; Std or Seq CSE. Serial measures of cardiac
      output indices, including minute distance, stroke distance, stroke volume, peak
      velocity, and corrected flow time, were recorded before and after intravascular
      fluid administration and after CSE. Women received either hyperbaric bupivacaine
      10 mg (Std) or 5 mg (Seq) with intrathecal fentanyl 15 microg. An epidural top-up
      with bupivacaine 0.5% w/v (5 mL at 20 min in the Std group and 10 mL at 15 min
      followed by 5 mL at 25 min in the Seq group) was given if predefined sensory
      targets were not met. Data were collected every 5 min after intrathecal
      injection. Hypotension was treated with ephedrine. Statistical analyses included
      repeated measures analysis of variance, analysis of covariance and Student's t
      test. P < 0.05 denoted significance. RESULTS: Results showed no difference in
      cardiac output, minute distance, stroke distance, stroke volume, peak velocity,
      or corrected flow time between groups over the first 20 min after spinal
      injection. For whole measurement periods, mean lowest values for these same
      measures showed no group differences. CONCLUSION: We therefore found no benefit
      in terms of cardiovascular stability of Seq to Std CSE for elective cesarean
      delivery in the healthy pregnant population.

PMID- 17000813
TI  - Difficult intubation in thyroid surgery: myth or reality?
AB  - Thyroid surgery is considered to be a risk factor for difficult airway
      management. We prospectively studied 324 consecutive patients undergoing thyroid
      surgery to investigate the incidence of difficult intubation as evaluated by the
      intubation difficulty scale as well as other specific predictive factors. The
      overall incidence of difficult intubation was 11.1% (95% CI: 7.6-14.5). Median
      intubation difficulty scale was 0 (25th-75th percentile: 0; 2.7). In three
      predefined groups (no echographic goiter, clinically palpable goiter, and
      impalpable goiter), difficult intubation occurred in 10% (95% CI: 4.8-17.4), 13%
      (95% CI: 6.5-18.4), and 11% (95% CI: 4.7-16.8) of patients, respectively, with no
      statistical difference among the groups. Specific predictive criteria (palpable
      goiter, endothoracic goiter, airway deformation, airway compression, or thyroid
      malignancy) were not associated with an increased rate of difficult intubation.
      Classical predictive criteria (mouth opening <35 mm, Mallampati III or IV, short
      neck, neck mobility <80 degrees , thyromental distance <65 mm, and a retrognathic
      mandible) were significantly reliable in the univariate analysis as risk factors
      for difficult intubation.

PMID- 17000814
TI  - Thawing procedures and the time course of clotting factor activity in fresh
      frozen plasma: a controlled laboratory investigation.
AB  - BACKGROUND: In this study, we evaluated the effects of the thawing process of 2
      commercially available devices on the activity of clotting factors, inhibitors
      and activation markers of the hemostatic system in fresh-frozen plasma (FFP). In
      an experimental procedure, FFP was thawed under running warm water at 42 degrees
      C. METHODS: Plasma of 20 healthy donors was sampled, separated, and distributed
      in 3 plasma bags. Within 2 h after sampling plasma bags was frozen at a
      temperature of -30 degrees C to -40 degrees C and stored for at least 8 wk. After
      sampling (baseline) as well as immediately and 1, 2, 4, and 6 h after thawing,
      the activity of FV, FVII, FVIII, fibrinogen, fibrin monomers (FM), d-dimers (DD),
      alpha2-antiplasmin (alpha2-AP), and protein S (PS) was determined from each
      plasma bag. RESULTS: From 1 h to 6 h after thawing, no significant differences in
      the activity of the investigated coagulation markers dependent on the thawing
      procedure were found. However, immediately after thawing and independent of the
      thawing procedure, the activity of FVII was significantly decreased (P < 0.01),
      whereas FM were significantly increased (P = 0.001). CONCLUSION: The thawing
      procedures studied exhibited no significant influence on activity and stability
      of the investigated markers of coagulation over the study period. The decreased
      activity of FVII and the clinical significance of the increase in FM require
      further research.

PMID- 17000815
TI  - Integrating the science of consciousness and anesthesia.
AB  - The nature and mechanism of human consciousness is emerging as one of the most
      important scientific and philosophical questions of the 21st century. Disregarded
      as a subject of serious inquiry throughout most of the 20th century, it has now
      regained legitimacy as a scientific endeavor. The investigation of consciousness
      and the mechanisms of general anesthesia have begun to converge. In the present
      article I provide an introduction to the study of consciousness, describe the
      neural correlates of consciousness that may be targets of general anesthetics,
      and suggest an integrated approach to the science of consciousness and
      anesthesia.

PMID- 17000816
TI  - Malignant hyperthermia in China.
AB  - Malignant hyperthermia has rarely been reported in China. We report the first
      case of malignant hyperthermia, verified by caffeine-halothane contracture test
      and genetic testing, in a Chinese patient.

PMID- 17000817
TI  - Fulminant liver failure after radical prostatectomy in the hyperlordotic
      position.
AB  - In the hyperlordotic position, the patient's hips are above the feet and head.
      This position has previously been associated with partial vena caval occlusion,
      increased venous pressures, and spinal cord infarction. We describe a case of
      fulminant hepatic failure after radical retropubic prostatectomy performed in the
      hyperlordotic position.

PMID- 17000818
TI  - A comparison of intrathecal morphine/fentanyl and patient-controlled analgesia
      with patient-controlled analgesia alone for analgesia after liver resection.
AB  - Continuous epidural anesthesia and analgesia may be considered in liver
      resection, but is often avoided because of the potential development of
      coagulopathies and the risk of epidural hematoma. In this prospective,
      randomized, double-blind study we compared postoperative morphine consumption via
      patient-controlled analgesia after liver surgery between two groups of patients:
      patients receiving a preoperative dose of intrathecal morphine (0.5 mg) and
      fentanyl (15 microg) (treatment group) and patients receiving a sham intrathecal
      injection (placebo group). Forty patients scheduled for major liver resection (>
      or = two segments) were enrolled. The primary outcome measure was patient
      controlled analgesia morphine consumption. Secondary outcomes were evaluation of
      pain at rest and with movement, scored on a visual analog scale with assessment
      of sedation, nausea, pruritus, and respiratory frequency. Outcome measures were
      recorded at 6, 12, 18, 24, and 48 h postspinal anesthesia or simulation. Patients
      in the placebo group consumed approximately three times more morphine during each
      time interval than patients in the treatment group (at 48 h: 124 +/- 30 vs 47 +/-
      21 mg, P < 0.0001). Pain evaluation on the visual analog scale was lower for the
      first 18 h in the treatment group. There was no difference in the incidence of
      side effects in both groups. Intrathecal morphine (0.5 mg) and fentanyl (15
      microg) given before liver surgery significantly decreased postoperative morphine
      consumption compared to placebo without any increase in side effects.

PMID- 17000819
TI  - The associations between severity of early postoperative pain, chronic
      postsurgical pain and plasma concentration of stable nitric oxide products after
      breast surgery.
AB  - In this study, we compared the effects of two analgesic regimens on perioperative
      nitric oxide index (NOx) and the likelihood of subsequent development of chronic
      postsurgical pain (CPSP) after breast surgery and sought to determine the
      association among early postoperative pain, NOx, and the likelihood of subsequent
      development of CPSP. Twenty-nine consecutive ASA I or II patients undergoing
      breast surgery with axillary clearance were randomly allocated to one of two
      groups. Patients in group S (n = 15) received a standard intraoperative and
      postoperative analgesic regimen (morphine sulfate, diclofenac, dextropropoxyphene
      hydrochloride + acetaminophen prn). Patients in group N (n = 14) received a
      continuous paravertebral block (for 48 h) and acetaminophen and parecoxib
      (followed by celecoxib up to 5 days). Visual analog scale pain scores at rest and
      on arm movement were recorded regularly until the fifth postoperative day. A
      telephone interview was conducted 10 wk postoperatively. The McGill Pain
      Questionnaire was used to characterize pain. NOx was estimated preoperatively, at
      the end of surgery, 30 min and 2, 4, 12, 24, 48 h postoperatively. Twelve (80%)
      patients in group S and no patient in group N developed CPSP (P = 0.009).
      Compared with patients with a pain rating index > or =1 (n = 18) 10 wk
      postoperatively, patients with a pain rating index = 0 (n = 11) had lesser visual
      analog scale pain scores on movement at each postoperative time point from 30 min
      until 96 h postoperatively (P < 0.005) and at rest 30 min (0.6 +/- 1.5 versus
      30.2 +/- 26.8; P = 0.004), 4 h (2.3 +/- 7.5 versus 19.0 +/- 25.8; P = 0.013), 8 h
      (4.4 +/- 10.2 versus 21.4 +/- 27.0; P = 0.03) and 12 h (0.7 +/- 1.2 versus 15.4
      +/- 27.0; P = 0.035) postoperatively. NOx values were greater in group N compared
      with group S 48 h postoperatively (40.6 +/- 20.1 versus 26.4 +/- 13.5; P = 0.04).

PMID- 17000820
TI  - An evaluation of the efficacy of aspirin and benzydamine hydrochloride gargle for
      attenuating postoperative sore throat: a prospective, randomized, single-blind
      study.
AB  - Postoperative sore throat (POST), although a minor complication, remains a source
      of postoperative morbidity. We compared the efficacy of dispersible aspirin
      gargle to benzydamine hydrochloride (a topical nonsteroidal anti inflammatory
      drug) gargles for prevention of POST. We enrolled 60 consecutive female patients,
      16-60 yr of age, ASA physical status I or II, undergoing elective modified
      radical mastectomy under general anesthesia in this prospective, randomized,
      placebo-controlled, single-blind study. Patients were randomly divided into 3
      groups of 20 subjects each: Group 1 (C) mineral water; Group 2 (AS) tab aspirin
      350 mg; and Group 3 (BH) 15 mL of benzydamine hydrochloride (0.15%). All the
      medications were made into 30 mL of solution. Patients were asked to gargle this
      mixture for 30 s, 5 min before induction of anesthesia. Grading of POST was done
      at 0, 2, 4, and 24 h postoperatively on a 4-point scale (0-3). Aspirin gargles
      reduced the incidence of POST for 4 h whereas benzydamine hydrochloride gargles
      reduced POST for 24 h. POST was more severe in the control group at 0 and 2 h (P
      < 0.05). Aspirin and benzydamine hydrochloride gargles significantly reduced the
      incidence and severity of POST (P < 0.05).

PMID- 17000821
TI  - The characteristics of intravenous adenosine-induced antinociception in a rabbit
      model of acute nociceptive pain: a comparative study with remifentanil.
AB  - BACKGROUND: Adenosine and remifentanil are potent IV analgesics with ultrashort
      half-lives. The antinociceptive effect of IV adenosine has not been clearly
      characterized. We compared the antinociceptive effects of adenosine and
      remifentanil in rabbits. METHODS: Sixteen rabbits, placed on a sling allowing
      reasonably free movement, received IV adenosine (400 microg x kg(-1) x min(-1))
      or remifentanil (0.4 microg x kg(-1) x min(-1)) over 240 min. RESULTS: Both drugs
      produced profound antinociception, as assessed by the number of animals
      unresponsive to clamping the forepaw and the electrical stimulation threshold of
      escape movement. With remifentanil, the antinociceptive effect increased rapidly,
      reaching its peak at 60 min, and then began to decline despite continued
      infusion. After stopping the infusion, it decreased rapidly and disappeared
      within 30 min. The vasodilating effect of IV adenosine was immediate in onset and
      ultrashort in duration. The antinociceptive effect of adenosine increased slowly
      but progressively during the infusion, reaching its peak only when the infusion
      ended. Then it decreased slowly over the following 360 min after terminating the
      infusion. CONCLUSION: Remifentanil had a rapid onset and short duration of
      action, and probably showed signs of tolerance development, whereas the
      antinocieptive effect of adenosine was slow in onset and long-lasting, despite
      its ultrashort plasma half-life and the immediate on-off profiles of its
      vasodilating effect.

PMID- 17000822
TI  - A genetic association study of the functional A118G polymorphism of the human mu
      opioid receptor gene in patients with acute and chronic pain.
AB  - In this prospective, observational study we explored whether A118G single
      nucleotide polymorphism in the human mu-opioid receptor (MOR) gene could explain
      the inter-individual differences in opioid analgesic requirements in patients
      with acute postoperative pain and chronic pain. The frequency of the wild-type
      A118 MOR (major) and variant G118 MOR (minor) alleles in the subjects with
      chronic, noncancer pain (n = 121) and opioid-naive subjects with acute
      postoperative pain (n = 101), serving as the control group, were examined. The
      relationships among the A118G MOR genotype, opioid requirements, and the
      numerical pain score were analyzed in both groups. The frequency of the minor
      allele was significantly lower in the subjects with chronic pain when compared
      with the group with acute postoperative pain (0.079 versus 0.158; P = 0.009 by
      chi2 test). No statistically significant association was observed between the
      presence of A118G MOR polymorphism and the average postoperative pain score or
      the doses of morphine used in the immediate postoperative period. In the high
      quartile, opioid utilization, chronic pain patients, the homozygotic carriers of
      the major allele required significantly higher opioid dose than did the carriers
      of the minor allele. The results indicate that although the presence of the minor
      allele does not appear to affect opioid analgesic use in acute postoperative
      pain, the minor allele is less common in chronic pain patients, especially in
      those requiring higher doses of opioid analgesics.

PMID- 17000824
TI  - An analysis of postoperative epidural analgesia failure by computed tomography
      epidurography.
AB  - In this prospective study involving 125 patients, we analyzed epidural analgesia
      failure after major abdominal surgery using computed tomography (CT)
      epidurographies to compare the incidence of dislodgement of epidural catheters
      and leakage of solution from the epidural space between two groups of patients:
      patients with successful or failed epidural analgesia. Our hypothesis was that
      the incidence of dislodgement and leakage should be low when epidural analgesia
      is successful. A thoracic epidural catheter was inserted before general
      anesthesia and secured by subcutaneous tunneling. Bupivacaine (0.25%) was
      administered during surgery followed by continuous epidural analgesia with 0.125%
      bupivacaine (10 mL/h) and morphine (0.25 mg/h) for 48 h. Failure was defined as a
      visual analog scale pain score at rest more than 30 mm and/or interruption of
      epidural analgesia before 48 h for any reason. When failure was not due to
      unintentionally withdrawn, kinked catheters or adverse events (n = 11), a CT scan
      with contrast injection was performed. Control CT scans were also performed in
      patients with adequate analgesia (i.e., the success group). The incidence of
      failure was 24.8% (n = 31). CT scans in the failure group (n = 20) showed seven
      patients with catheters outside the epidural space, nine with normal
      distribution, one with unilateral spread, and three with leakage of solution
      outside the epidural space. In the success group, CT scans (n = 19) showed 11
      patients with normal distribution, five with unilateral spread, and three with
      leakage. We conclude that the major cause of epidural analgesia failure was
      dislodgment of the catheter. CT scans were mostly useful for detecting leakage of
      injectate, which may be the early phase of dislodgment.

PMID- 17000823
TI  - A comparison of neuraxial block versus general anesthesia for elective total hip
      replacement: a meta-analysis.
AB  - BACKGROUND: A recent meta-analysis showed that compared with general anesthesia
      (GA), neuraxial block reduced many serious complications in patients undergoing
      various types of surgeries. It is not known whether this finding from studying
      heterogeneous patient groups is applicable to a particular surgical patient
      population. We performed the present meta-analysis to determine whether
      anesthesia choice affected the outcome after elective total hip replacement
      (THR). METHODS: Medline (1966 to August 2005), MD Consult (1966 to August 2005),
      BIOSIS (1969 to August 2005), and EMBASE (1969 to August 2005) databases were
      searched. Randomized and quasi randomized studies comparing GA and neuraxial
      (spinal or epidural) block for elective THR were included in this analysis.
      RESULTS: Ten independent trials, involving 330 patients under GA and 348 patients
      under neuraxial block, were identified and analyzed. Pooled results from five
      trials showed that neuraxial block significantly decreased the incidence of
      radiographically diagnosed deep venous thrombosis or pulmonary embolism. The odds
      ratio (OR) for deep venous thrombosis was 0.27 with 95% confidence interval (CI)
      0.17-0.42. The OR for pulmonary embolism was 0.26 with 95% CI 0.12-0.56.
      Neuraxial block also decreased the operative time by 7.1 min/case (95% CI 2.3
      11.9 min) and intraoperative blood loss by 275 mL/case (95% CI 180-371 mL). Data
      from three trials showed that patients under neuraxial block for THR were less
      likely to require blood transfusion than were patients under GA (21/177 = 12% vs
      62/188 = 33% of patients transfused, P < 0.001 by z-test). The OR for this
      comparison was 0.26. However, the CIs were wide and compatible with both no
      effect and a nine-tenths reduction (95% CI 0.06-1.05). CONCLUSIONS: Patients
      undergoing elective THR under neuraxial anesthesia seem to have better outcomes
      than those under GA.

PMID- 17000825
TI  - Ultrasound-guided intercostal nerve cryoablation.
AB  - Ultrasound technology has advanced regional anesthesia and pain management, by
      improving accuracy and reducing complication rates. We have successfully
      performed cryoablation of intercostal nerves with ultrasound guidance with no
      complications. Four patients with postthoracotomy pain syndrome had pain relief
      for at least 1 mo after selective cryoablation of intercostal nerves at the mid
      axillary line. Visualizing the pleura during the procedure is the greatest
      benefit of using ultrasonography, especially in thin patients whose intercostal
      groove to pleural distance may be <0.5 cm. Although further studies are needed,
      we feel that this new technique should reduce the risk of pneumothorax as well as
      improve the success of cryoablation.

PMID- 17000826
TI  - Bleeding complications from femoral and sciatic nerve catheters in patients
      receiving low molecular weight heparin.
AB  - After knee replacement surgery, the use of continuous local anesthetic infusions
      in femoral and sciatic peripheral nerve catheters is an effective analgesic
      option. Limited data are available concerning the safety of peripheral nerve
      infusions in patients receiving low molecular weight heparin thromboprophylaxis.
      We report three cases of bleeding at femoral and sciatic catheter sites in
      patients receiving a single daily dose of enoxaparin (40 mg). In all cases, some
      bleeding was noticed before catheter removal; in one case involving catheter
      removal 3 h after enoxaparin administration, massive thigh swelling occurred.
      Physical therapy and discharge from the hospital were delayed in two cases but no
      other complications were seen. More data are needed to determine if it is
      necessary to use the same guidelines for managing peripheral nerve infusion
      catheters in patients receiving enoxaparin as with epidurals and other types of
      central nerve catheter infusions.

PMID- 17000827
TI  - In defense of the peripheral nerve stimulation technique.

PMID- 17000828
TI  - Improved design of level 1 air detection system.

PMID- 17000829
TI  - Tracheobronchomalacia-like lung collapse during three separate trials of general
      anesthesia.

PMID- 17000830
TI  - Supplemental intravenous crystalloid administration and risk of surgical wound
      infection.

PMID- 17000831
TI  - A new technique for removal of endotracheal tube.

PMID- 17000832
TI  - Anesthetic management of radiofrequency ablation of mediastinal metastatic lymph
      nodes adjacent to the trachea.

PMID- 17000833
TI  - A simple method to apply continuous positive airway pressure during the use of a
      Univent tube.

PMID- 17000834
TI  - Glidescope video laryngoscope is useful in exchanging endotracheal tubes.

PMID- 17000835
TI  - November 2005 Food and Drug Administration Alert: risk of electromagnetic
      interference with medical telemetry systems operating in the 460-470 MHz
      frequency bands.

PMID- 17000836
TI  - Size 1 ProSeal laryngeal mask airway in neonates.

PMID- 17000837
TI  - Local anesthetic effect on liver function.

PMID- 17000838
TI  - Safety of the posterior approach to the brachial plexus.

PMID- 17000839
TI  - Persisting neurological symptoms after uncomplicated intrathecal bupivacaine.

PMID- 17000840
TI  - The "double bubble" sign for successful infraclavicular brachial plexus blockade.

PMID- 17000841
TI  - Supplying sub-100% oxygen gas mixtures during monitored anesthesia care:
      respiratory monitoring and use of a venturi device.

PMID- 17000842
TI  - BIS and the electromyogram.

PMID- 17000843
TI  - Propofol infusion syndrome--a fatal case at a low infusion rate.

PMID- 17000844
TI  - Preventing operating room fire: an alternate approach.

PMID- 17000845
TI  - Transient urinary incontinence after subarachnoid anesthesia with 0.5% heavy
      bupivacaine.

PMID- 17000846
TI  - Laryngeal mask airway and tonsillectomy.

PMID- 17000847
TI  - Blink reflex for trigeminal nerve block or blind local anesthetic infiltration.

PMID- 17000848
TI  - Renal protection with isoflurane.

PMID- 17000849
TI  - The effect of different arrangements of T-piece parts on oxygenation of patients
      with tracheostomy.

PMID- 17000850
TI  - Disposable breathing circuit tubing as a safety sleeve.

PMID- 17000851
TI  - Percutaneous dilational tracheostomy kit: an aid to submental intubation.

PMID- 17000852
TI  - Reproducibility of the corticotropin stimulation test in septic shock.

PMID- 17000853
TI  - Another defect in right-angle double connector resulting in high peak inspiratory
      pressure during one lung anesthesia: a simple and practical approach for rapid
      detection.

PMID- 17000854
TI  - General versus regional: why either/or?

PMID- 17000855
TI  - What is the correct temperature management of the febrile patient?

PMID- 17000856
TI  - Dental mirror is a relief for difficult endotracheal intubation.

PMID- 17000857
TI  - The caterpillar technique for removal of a tight ring.

PMID- 17000858
TI  - Respiratory failure after lumbar epidural anesthesia in a patient with
      uncontrolled hyperthyroidism.

PMID- 17000859
TI  - Postoperative renal failure after aprotinin infusion and spine operations.

PMID- 17000860
TI  - A simple technique to avoid traumatic nasal intubation.

PMID- 17000861
TI  - Neurotoxicity of domoic Acid in cerebellar granule neurons in a genetic model of
      glutathione deficiency.
AB  - This study investigated the role of cellular antioxidant defense mechanisms in
      modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule
      neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine
      ligase (Gclm). Glutamate-cysteine ligase (Glc) catalyzes the first and rate
      limiting step in glutathione (GSH) biosynthesis. CGNs from Gclm (-/-) mice have
      very low levels of GSH and are 10-fold more sensitive to DomA-induced toxicity
      than CGNs from Gclm (+/+) mice. GSH ethyl ester decreased, whereas the Gcl
      inhibitor buthionine sulfoximine increased DomA toxicity. Antagonists of alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors and of N
      methyl-D-aspartate (NMDA) receptors blocked DomA toxicity, and NMDA receptors
      were activated by DomA-induced l-glutamate release. The differential
      susceptibility of CGNs to DomA toxicity was not due to a differential expression
      of ionotropic glutamate receptors, as evidenced by similar calcium responses and
      L-glutamate release in the two genotypes. A calcium chelator and several
      antioxidants antagonized DomA-induced toxicity. DomA caused a rapid decrease in
      cellular GSH, which preceded toxicity, and the decrease was primarily due to DomA
      induced GSH efflux. DomA also caused an increase in oxidative stress as indicated
      by increases in reactive oxygen species and lipid peroxidation, which was
      subsequent to GSH efflux. Astrocytes from both genotypes were resistant to DomA
      toxicity and presented a diminished calcium response to DomA and a lack of DomA
      induced L-glutamate release. Because polymorphisms in the GCLM gene in humans are
      associated with low GSH levels, such individuals, as well as others with genetic
      conditions or environmental exposures that lead to GSH deficiency, may be more
      susceptible to DomA-induced neurotoxicity.

PMID- 17000862
TI  - Baffled by bafilomycin: an anticancer agent that induces hypoxia-inducible factor
      1alpha expression.
AB  - In an article presented in this issue of Molecular Pharmacology, Lim et al. (p.
      1856) investigate the anticancer effect of bafilomycin, an inhibitor of the
      vacuolar ATPase. The authors report that bafilomycin inhibits cell cycle
      progression and tumor growth by inducing the expression of hypoxia-inducible
      factor (HIF) 1alpha and the cyclin-dependent kinase inhibitor p21(CIP1), a
      surprising result because HIF-1alpha overexpression is associated with tumor
      growth and angiogenesis in preclinical models and with increased patient
      mortality in clinical studies. However, the authors demonstrate that bafilomycin
      induced HIF-1alpha expression leads to increased CIP1 gene expression but does
      not lead to increased expression of other HIF-1-regulated genes that promote
      tumor progression.

PMID- 17000863
TI  - Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and
      Phe340(6.52) with superpotent N-benzyl phenethylamine agonists.
AB  - Experiments were conducted to examine the molecular basis for the high affinity
      and potency of a new class of 5-HT(2A) receptor agonists, N-benzyl
      phenethylamines. Competition binding assays at several serotonin receptors
      confirmed that an N-arylmethyl substitution was necessary for affinity increases
      up to 300-fold over simple N-alkyl homologs, as well as enhanced selectivity for
      5-HT(2A) versus 5-HT(2C) and 5-HT(1A) receptors. PI hydrolysis functional assays
      confirmed that these N-benzyl phenethylamines are potent and highly efficacious
      agonists at the rat 5-HT(2A) receptor. Virtual docking of these compounds into a
      human 5-HT(2A) receptor homology model indicated that the N-benzyl moiety might
      be interacting with Phe339((6.51)), whereas the phenethylamine portion was likely
      to be interacting with Phe340((6.52)). Experiments in h5-HT(2A) receptors with
      Phe339((6.51))L and Phe340((6.52))L mutations seem to support this hypothesis.
      Dramatic detrimental effects on affinity, potency, and intrinsic activity were
      observed with the Phe339((6.51))L mutation for all N-benzyl analogs, whereas most
      N-unsubstituted phenethylamines and traditional agonists were only weakly
      affected, if at all. Consistent with other published studies, the Phe340((6.52))L
      mutation detrimentally affected affinity, potency, and intrinsic activity of
      nearly all compounds tested, although a strong change in intrinsic activity was
      not seen with most N-aryl analogs. These data further validate the topology of
      our h5-HT(2A) receptor homology model. It is noteworthy that this study is the
      first to identify a hitherto unrecognized role for residue 6.51 in agonist
      activation of a serotonin G protein-coupled receptor (GPCR), whereas most
      previous reports have suggested a varied and sometimes contradictory role in
      homologous GPCRs.

PMID- 17000864
TI  - The H+-linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic
      target for high-risk neuroblastoma.
AB  - Neuroblastomas produce high amounts of lactic acid and upregulate the H(+)-linked
      monocarboxylate transporter isoform 1 (MCT1/SLC16A1). We found elevated MCT1 mRNA
      levels in fresh neuroblastoma biopsy samples that correlated positively with risk
      of fatal disease and amplification of the "proto-oncogenic" transcription factor
      MYCN. We further investigated MCT as a potential therapeutic target in vitro. The
      neuroblastoma cell lines evaluated were Sk-N-SH, CHP134, IMR32, and NGP. All
      lines exhibited decreased intracellular pH at low tumor-like extracellular pH.
      Lonidamine or exogenous lactate further lowered intracellular pH. Immediate early
      lowering of intracellular pH with lonidamine or lactate at extracellular pH 6.5
      correlated positively with diminished cell viability within 48 h. These findings
      indicate that MCT1 is a potential therapeutic target and that neuroblastoma
      therapy may be enhanced by therapeutic strategies to inhibit or overwhelm MCT.
      Additional experiments indicated that the mechanism of cell death by lonidamine
      or exogenous lactate is similar to that obtained using alpha-cyano-4-OH
      cinnamate, a well established MCT inhibitor. Because lactate production is also
      high in melanoma and many other tumor types, MCT inhibitors may have broad
      application in cancer treatment. Such treatment would have selectivity by virtue
      of the acidic milieu surrounding tumors, because MCT is increasingly active as
      extracellular pH decreases below 7.0 and lactic acid production increases.

PMID- 17000865
TI  - A Leishmania amazonensis ZIP family iron transporter is essential for parasite
      replication within macrophage phagolysosomes.
AB  - Infection of mammalian hosts with Leishmania amazonensis depends on the
      remarkable ability of these parasites to replicate within macrophage
      phagolysosomes. A critical adaptation for survival in this harsh environment is
      an efficient mechanism for gaining access to iron. In this study, we identify and
      characterize LIT1, a novel L. amazonensis membrane protein with extensive
      similarity to IRT1, a ZIP family ferrous iron transporter from Arabidopsis
      thaliana. The ability of LIT1 to promote iron transport was demonstrated after
      expression in yeast and in L. amazonensis LIT1-null amastigotes. Endogenous LIT1
      was only detectable in amastigotes replicating intracellularly, and its
      intracellular expression was accelerated under conditions predicted to result in
      iron deprivation. Although L. amazonensis lacking LIT1 grew normally in axenic
      culture and had no defects differentiating into infective forms, replication
      within macrophages was abolished. Consistent with an essential role for LIT1 in
      intracellular growth as amastigotes, Deltalit1 parasites were avirulent. After
      inoculation into highly susceptible mice, no lesions were detected, even after
      extensive periods of time. Despite the absence of pathology, viable Deltalit1
      parasites were recovered from the original sites of inoculation, indicating that
      L. amazonensis can persist in vivo independently of the ability to grow in
      macrophages. Our findings highlight the essential role played by intracellular
      iron acquisition in Leishmania virulence and identify this pathway as a promising
      target for therapeutic intervention.

PMID- 17000866
TI  - Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS
      induced trafficking of TLRs to lipid rafts.
AB  - Carbon monoxide (CO), a byproduct of heme catabolism by heme oxygenase (HO),
      confers potent antiinflammatory effects. Here we demonstrate that CO derived from
      HO-1 inhibited Toll-like receptor (TLR) 2, 4, 5, and 9 signaling, but not TLR3
      dependent signaling, in macrophages. Ligand-mediated receptor trafficking to
      lipid rafts represents an early event in signal initiation of immune cells.
      Trafficking of TLR4 to lipid rafts in response to LPS was reactive oxygen species
      (ROS) dependent because it was inhibited by diphenylene iodonium, an inhibitor of
      NADPH oxidase, and in gp91(phox)-deficient macrophages. CO selectively inhibited
      ligand-induced recruitment of TLR4 to lipid rafts, which was also associated with
      the inhibition of ligand-induced ROS production in macrophages. TLR3 did not
      translocate to lipid rafts by polyinosine-polycytidylic acid (poly(I:C)). CO had
      no effect on poly(I:C)-induced ROS production and TLR3 signaling. The inhibitory
      effect of CO on TLR-induced cytokine production was abolished in gp91(phox)
      deficient macrophages, also indicating a role for NADPH oxidase. CO attenuated
      LPS-induced NADPH oxidase activity in vitro, potentially by binding to
      gp91(phox). Thus, CO negatively controlled TLR signaling pathways by inhibiting
      translocation of TLR to lipid rafts through suppression of NADPH oxidase
      dependent ROS generation.

PMID- 17000867
TI  - Characterization of the defective interaction between a subset of natural killer
      cells and dendritic cells in HIV-1 infection.
AB  - In this study, we demonstrate that the in vitro interactions between a
      CD56(neg)/CD16(pos) (CD56(neg)) subset of natural killer (NK) cells and
      autologous dendritic cells (DCs) from HIV-1-infected viremic but not aviremic
      individuals are markedly impaired and likely interfere with the development of an
      effective immune response. Among the defective interactions are abnormalities in
      the process of reciprocal NK-DC activation and maturation as well as a defect in
      the NK cell-mediated editing or elimination of immature DCs (iDCs). Notably, the
      lysis of mature DCs (mDCs) by autologous NK cells was highly impaired even after
      the complete masking of major histocompatibility complex I molecules, suggesting
      that the defective elimination of autologous iDCs is at the level of activating
      NK cell receptors. In this regard, the markedly impaired expression/secretion and
      function of NKp30 and TNF-related apoptosis-inducing ligand, particularly among
      the CD56(neg) NK cell subset, largely accounts for the highly defective NK cell
      mediated lysis of autologous iDCs. Moreover, mDCs generated from HIV-1 viremic
      but not aviremic patients are substantially impaired in their ability to secrete
      interleukin (IL)-10 and -12 and to prime the proliferation of neighboring
      autologous NK cells, which, in turn, fail to secrete adequate amounts of
      interferon-gamma.

PMID- 17000868
TI  - Synergy between the pre-T cell receptor and Notch: cementing the alphabeta
      lineage choice.
AB  - Notch1 signaling suppresses B cell development and promotes T lineage commitment
      in thymus-seeding hematopoietic progenitors. Notch1 is also activated in early T
      cell progenitors, but the functions of these later Notch signals have not been
      clearly defined. Recent studies reveal that Notch signaling is not essential for
      pre-T cell receptor (TCR) expression or gammadelta lineage choice. Rather, pre
      TCR signaling enhances progenitor competitiveness for limiting Notch ligands,
      leading to preferential expansion of TCRbeta-bearing progenitors.

PMID- 17000869
TI  - Chewing the fat on natural killer T cell development.
AB  - Natural killer T cells (NKT cells) are selected in the thymus by self-glycolipid
      antigens presented by CD1d molecules. It is currently thought that one specific
      component of the lysosomal processing pathway, which leads to the production of
      isoglobotrihexosylceramide (iGb3), is essential for normal NKT cell development.
      New evidence now shows that NKT cell development can be disrupted by a diverse
      range of mutations that interfere with different elements of the lysosomal
      processing and degradation of glycolipids. This suggests that lysosomal storage
      diseases (LSDs) in general, rather than one specific defect, can disrupt CD1d
      antigen presentation, leading to impaired development of NKT cells.

PMID- 17000872
TI  - The power of music.

PMID- 17000870
TI  - Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade.
AB  - The programmed death (PD)-1-PD-1 ligand (PD-L) pathway, which is part of the B7
      CD28 family, consists of the PD-1 receptor and its two ligands PD-L1 and PD-L2.
      Engagement of PD-1 by its ligands inhibits immune responses, and recent work has
      shown that PD-1 is highly expressed on exhausted T cells during chronic
      lymphocytic choriomeningitis virus (LCMV) infection in mice. Blockade of this
      pathway reinvigorates the exhausted T cells, allowing them to expand and produce
      effector cytokines, raising the issue of whether this pathway has been exploited
      by a variety of viruses during chronic infection. New studies now extend these
      observations to HIV infection and human disease.

PMID- 17000873
TI  - For catch bonds, it all hinges on the interdomain region.
AB  - Tensile mechanical force was long assumed to increase the detachment rates of
      biological adhesive bonds (Bell, 1978). However, in the last few years, several
      receptor-ligand pairs were shown to form "catch bonds," whose lifetimes are
      enhanced by moderate amounts of force. These include the bacterial adhesive
      protein FimH binding to its ligand mannose (Thomas et al., 2002; Thomas et al.,
      2006), blood cell adhesion proteins P- and L-selectin binding to sialyl Lewis X
      (sLe(X))-containing ligands (Marshall et al., 2003; Evans et al., 2004;
      Sarangapani et al., 2004), and the myosin-actin motor protein interaction (Guo
      and Guilford, 2006). The structural mechanism behind this counterintuitive force
      enhanced catch bond behavior is of great interest.

PMID- 17000874
TI  - Autoinhibition regulates the motility of the C. elegans intraflagellar transport
      motor OSM-3.
AB  - OSM-3 is a Kinesin-2 family member from Caenorhabditis elegans that is involved
      in intraflagellar transport (IFT), a process essential for the construction and
      maintenance of sensory cilia. In this study, using a single-molecule fluorescence
      assay, we show that bacterially expressed OSM-3 in solution does not move
      processively (multiple steps along a microtubule without dissociation) and
      displays low microtubule-stimulated adenosine triphosphatase (ATPase) activity.
      However, a point mutation (G444E) in a predicted hinge region of OSM-3's coiled
      coil stalk as well as a deletion of that hinge activate ATPase activity and
      induce robust processive movement. These hinge mutations also cause a
      conformational change in OSM-3, causing it to adopt a more extended conformation.
      The motility of wild-type OSM-3 also can be activated by attaching the motor to
      beads in an optical trap, a situation that may mimic attachment to IFT cargo. Our
      results suggest that OSM-3 motility is repressed by an intramolecular interaction
      that involves folding about a central hinge and that IFT cargo binding relieves
      this autoinhibition in vivo. Interestingly, the G444E allele in C. elegans
      produces similar ciliary defects to an osm-3-null mutation, suggesting that
      autoinhibition is important for OSM-3's biological function.

PMID- 17000875
TI  - SUSP1 antagonizes formation of highly SUMO2/3-conjugated species.
AB  - Small ubiquitin-related modifier (SUMO) processing and deconjugation are mediated
      by sentrin-specific proteases/ubiquitin-like proteases (SENP/Ulps). We show that
      SUMO-specific protease 1 (SUSP1), a mammalian SENP/Ulp, localizes within the
      nucleoplasm. SUSP1 depletion within cell lines expressing enhanced green
      fluorescent protein (EGFP) fusions to individual SUMO paralogues caused
      redistribution of EGFP-SUMO2 and -SUMO3, particularly into promyelocytic leukemia
      (PML) bodies. Further analysis suggested that this change resulted primarily from
      a deficit of SUMO2/3-deconjugation activity. Under these circumstances, PML
      bodies became enlarged and increased in number. We did not observe a comparable
      redistribution of EGFP-SUMO1. We have investigated the specificity of SUSP1 using
      vinyl sulfone inhibitors and model substrates. We found that SUSP1 has a strong
      paralogue bias toward SUMO2/3 and that it acts preferentially on substrates
      containing three or more SUMO2/3 moieties. Together, our findings argue that
      SUSP1 may play a specialized role in dismantling highly conjugated SUMO2 and -3
      species that is critical for PML body maintenance.

PMID- 17000876
TI  - Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin
      3.
AB  - Misfolded proteins of the endoplasmic reticulum undergo retrotranslocation to
      enter the cytosol where they are degraded by the proteasome. Retrotranslocation
      of many substrates requires an ATPase complex consisting of the p97 ATPase and a
      dimeric cofactor, Ufd1-Npl4. We report that efficient elimination of misfolded ER
      proteins also involves ataxin-3 (atx3), a p97-associated deubiquitinating enzyme
      mutated in type-3 spinocerebellar ataxia. Overexpression of an atx3 mutant
      defective in deubiquitination inhibits the degradation of misfolded ER proteins
      and triggers ER stress. Misfolded polypeptides stabilized by mutant atx3 are
      accumulated in part as polyubiquitinated form, suggesting an involvement of its
      deubiquitinating activity in ER-associated protein degradation regulation. We
      demonstrate that atx3 transiently associates with the ER membrane via p97 and the
      recently identified Derlin-VIMP complex, and its release from the membrane
      appears to be governed by both the p97 ATPase cycle and its own deubiquitinating
      activity. We present evidence that atx3 may promote p97-associated
      deubiquitination to facilitate the transfer of polypeptides from p97 to the
      proteasome.

PMID- 17000877
TI  - Exomer: A coat complex for transport of select membrane proteins from the trans
      Golgi network to the plasma membrane in yeast.
AB  - A yeast plasma membrane protein, Chs3p, transits to the mother-bud neck from a
      reservoir comprising the trans-Golgi network (TGN) and endosomal system. Two
      TGN/endosomal peripheral proteins, Chs5p and Chs6p, and three Chs6p paralogues
      form a complex that is required for the TGN to cell surface transport of Chs3p.
      The role of these peripheral proteins has not been clear, and we now provide
      evidence that they create a coat complex required for the capture of membrane
      proteins en route to the cell surface. Sec7p, a Golgi protein required for
      general membrane traffic and functioning as a nucleotide exchange factor for the
      guanosine triphosphate (GTP)-binding protein Arf1p, is required to recruit Chs5p
      to the TGN surface in vivo. Recombinant forms of Chs5p, Chs6p, and the Chs6p
      paralogues expressed in baculovirus form a complex of approximately 1 MD that
      binds synthetic liposomes in a reaction requiring acidic phospholipids, Arf1p,
      and the nonhydrolyzable GTPgammaS. The complex remains bound to liposomes
      centrifuged on a sucrose density gradient. Thin section electron microscopy
      reveals a spiky coat structure on liposomes incubated with the full complex,
      Arf1p, and GTPgammaS. We termed the novel coat exomer for its role in exocytosis
      from the TGN to the cell surface. Unlike other coats (e.g., coat protein complex
      I, II, and clathrin/adaptor protein complex), the exomer does not form buds or
      vesicles on liposomes.

PMID- 17000878
TI  - A novel role for phagocytosis-like uptake in herpes simplex virus entry.
AB  - It is becoming increasingly clear that herpesviruses can exploit the endocytic
      pathway to infect cells, yet several important features of this process remain
      poorly defined. Using herpes simplex virus-1 (HSV-1) as a model, we demonstrate
      that endocytosis of the virions mimic many features of phagocytosis. During
      entry, HSV-1 virions associated with plasma membrane protrusions followed by a
      phagocytosis-like uptake involving rearrangement of actin cytoskeleton and
      trafficking of the virions in large phagosome-like vesicles. RhoA GTPase was
      activated during this process and the mode of entry was cell type-specific.
      Clathrin-coated vesicles had no detectable role in virion trafficking as Eps15
      dominant-negative mutants failed to affect HSV-1 uptake. Binding and fusion of
      the virion envelope with the phagosomal membrane is likely facilitated by
      clustering of nectin-1 (or HVEM) in phagosomes, which was observed in infected
      cells. Collectively, our data suggests a novel mode of uptake by which the virus
      can infect both professional and nonprofessional phagocytes.

PMID- 17000879
TI  - Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte
      invasion by the malaria parasite.
AB  - Apicomplexan pathogens are obligate intracellular parasites. To enter cells, they
      must bind with high affinity to host cell receptors and then uncouple these
      interactions to complete invasion. Merozoites of Plasmodium falciparum, the
      parasite responsible for the most dangerous form of malaria, invade erythrocytes
      using a family of adhesins called Duffy binding ligand-erythrocyte binding
      proteins (DBL-EBPs). The best-characterized P. falciparum DBL-EBP is erythrocyte
      binding antigen 175 (EBA-175), which binds erythrocyte surface glycophorin A. We
      report that EBA-175 is shed from the merozoite at around the point of invasion.
      Shedding occurs by proteolytic cleavage within the transmembrane domain (TMD) at
      a site that is conserved across the DBL-EBP family. We show that EBA-175 is
      cleaved by PfROM4, a rhomboid protease that localizes to the merozoite plasma
      membrane, but not by other rhomboids tested. Mutations within the EBA-175 TMD
      that abolish cleavage by PfROM4 prevent parasite growth. Our results identify a
      crucial role for intramembrane proteolysis in the life cycle of this pathogen.

PMID- 17000880
TI  - Mechanism of transport of IFT particles in C. elegans cilia by the concerted
      action of kinesin-II and OSM-3 motors.
AB  - The assembly and function of cilia on Caenorhabditis elegans neurons depends on
      the action of two kinesin-2 motors, heterotrimeric kinesin-II and homodimeric OSM
      3-kinesin, which cooperate to move the same intraflagellar transport (IFT)
      particles along microtubule (MT) doublets. Using competitive in vitro MT gliding
      assays, we show that purified kinesin-II and OSM-3 cooperate to generate movement
      similar to that seen along the cilium in the absence of any additional regulatory
      factors. Quantitative modeling suggests that this could reflect an alternating
      action mechanism, in which the motors take turns to move along MTs, or a
      mechanical competition, in which the motors function in a concerted fashion to
      move along MTs with the slow motor exerting drag on the fast motor and vice
      versa. In vivo transport assays performed in Bardet-Biedl syndrome (BBS) protein
      and IFT motor mutants favor a mechanical competition model for motor coordination
      in which the IFT motors exert a BBS protein-dependent tension on IFT particles,
      which controls the IFT pathway that builds the cilium foundation.

PMID- 17000881
TI  - An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis.
AB  - Establishment of angiogenic circuits that orchestrate blood vessel development
      and remodeling requires an exquisite balance between the activities of pro- and
      antiangiogenic factors. However, the logic that permits complex signal
      integration by vascular endothelium is poorly understood. We demonstrate that a
      "neuropeptide," neurokinin-B (NK-B), reversibly inhibits endothelial cell
      vascular network assembly and opposes angiogenesis in the chicken chorioallantoic
      membrane. Disruption of endogenous NK-B signaling promoted angiogenesis.
      Mechanistic analyses defined a multicomponent pathway in which NK-B signaling
      converges upon cellular processes essential for angiogenesis. NK-B-mediated
      ablation of Ca2+ oscillations and elevation of 3'-5' [corrected] cyclic adenosine
      monophosphate (cAMP) reduced cellular proliferation, migration, and vascular
      endothelial growth factor receptor expression and induced the antiangiogenic
      protein calreticulin. Whereas NK-B initiated certain responses, other activities
      required additional stimuli that increase cAMP. Although NK-B is a
      neurotransmitter/ neuromodulator and NK-B overexpression characterizes the
      pregnancy-associated disorder preeclampsia, NK-B had not been linked to vascular
      remodeling. These results establish a conserved mechanism in which NK-B
      instigates multiple activities that collectively oppose vascular remodeling.

PMID- 17000882
TI  - NCAM promotes assembly and activity-dependent remodeling of the postsynaptic
      signaling complex.
AB  - The neural cell adhesion molecule (NCAM) regulates synapse formation and synaptic
      strength via mechanisms that have remained unknown. We show that NCAM associates
      with the postsynaptic spectrin-based scaffold, cross-linking NCAM with the N
      methyl-d-aspartate (NMDA) receptor and Ca2+/calmodulin-dependent protein kinase
      II alpha (CaMKIIalpha) in a manner not firmly or directly linked to PSD95 and
      alpha-actinin. Clustering of NCAM promotes formation of detergent-insoluble
      complexes enriched in postsynaptic proteins and resembling postsynaptic
      densities. Disruption of the NCAM-spectrin complex decreases the size of
      postsynaptic densities and reduces synaptic targeting of NCAM-spectrin-associated
      postsynaptic proteins, including spectrin, NMDA receptors, and CaMKIIalpha.
      Degeneration of the spectrin scaffold in NCAM-deficient neurons results in an
      inability to recruit CaMKIIalpha to synapses after NMDA receptor activation,
      which is a critical process in NMDA receptor-dependent long-term potentiation.
      The combined observations indicate that NCAM promotes assembly of the spectrin
      based postsynaptic signaling complex, which is required for activity-associated,
      long-lasting changes in synaptic strength. Its abnormal function may contribute
      to the etiology of neuropsychiatric disorders associated with mutations in or
      abnormal expression of NCAM.

PMID- 17000884
TI  - Secondary prevention of venous thromboembolic events in patients with active
      cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180
      day period.
AB  - This study evaluated enoxaparin alone versus initial enoxaparin followed by
      warfarin in secondary prevention of venous thromboembolic events in adults with
      active malignancy. Cancer patients (n = 122) with acute symptomatic venous
      thromboembolic events were randomly allocated to receive subcutaneous enoxaparin
      1.0 mg/kg every 12 hours for 5 days, followed by 1.0 mg/kg daily (group 1a) or
      1.5 mg/kg daily (group 1b) for 175 days, or subcutaneous enoxaparin 1.0 mg/kg
      every 12 hours for at least 5 days and until a stable international normalized
      ratio of 2 to 3 was achieved on oral warfarin begun on day 2 and continued to day
      180 (group 2). There were no significant differences in major and minor bleeding
      rates between treatment groups. No bleeding events were intracranial or fatal.
      Enoxaparin treatment was feasible, generally well tolerated, and effective for a
      180-day period in the secondary prevention of venous thromboembolic events in
      patients with active malignancy.

PMID- 17000883
TI  - Flow-enhanced adhesion regulated by a selectin interdomain hinge.
AB  - L-selectin requires a threshold shear to enable leukocytes to tether to and roll
      on vascular surfaces. Transport mechanisms govern flow-enhanced tethering,
      whereas force governs flow-enhanced rolling by prolonging the lifetimes of L
      selectin-ligand complexes (catch bonds). Using selectin crystal structures,
      molecular dynamics simulations, site-directed mutagenesis, single-molecule force
      and kinetics experiments, Monte Carlo modeling, and flow chamber adhesion
      studies, we show that eliminating a hydrogen bond to increase the flexibility of
      an interdomain hinge in L-selectin reduced the shear threshold for adhesion via
      two mechanisms. One affects the on-rate by increasing tethering through greater
      rotational diffusion. The other affects the off-rate by strengthening rolling
      through augmented catch bonds with longer lifetimes at smaller forces. By forcing
      open the hinge angle, ligand may slide across its interface with L-selectin to
      promote rebinding, thereby providing a mechanism for catch bonds. Thus,
      allosteric changes remote from the ligand-binding interface regulate both bond
      formation and dissociation.

PMID- 17000885
TI  - Classification and characterization of hereditary types 2A, 2B, 2C, 2D, 2E, 2M,
      2N, and 2U (unclassifiable) von Willebrand disease.
AB  - All variants of type 2 von Willebrand disease (VWD) patients, except 2N, show a
      defective von Willebrand factor (VWF) protein (on cross immunoelectrophoresis or
      multimeric analysis), decreased ratios for VWF:RCo/Ag and VWF:CB/Ag and prolonged
      bleeding time. The bleeding time is normal and FVIII:C levels are clearly lower
      than VWF:Ag in type 2N VWD. High resolution multimeric analysis of VWF in plasma
      demonstrates that proteolysis of VWF is increased in type 2A and 2B VWD with
      increased triplet structure of each visuable band (not present in types 2M and
      2U), and that proteolysis of VWF is minimal in type 2C, 2D, and 2E variants that
      show aberrant multimeric structure of individual oligomers. VWD 2B differs from
      2A by normal VWF in platelets, and increased ristocetine-induced platelet
      aggregation (RIPA). RIPA, which very likely reflects the VWF content of
      platelets, is normal in mild, decreased in moderate, and absent in severe type 2A
      VWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D, variable in 2E, and
      normal in 2N. VWD 2M is usually mild and characterized by decreased VWF:RCo and
      RIPA, a normal or near normal VWF multimeric pattern in a low resolution agarose
      gel. VWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically
      featured by low VWF:RCo and RIPA with the relative lack of high large VWF
      multimers. VWD type 2C is recessive and shows a characteristic multimeric pattern
      with a lack of high molecular weight multimers, the presence of one single-banded
      multimers instead of triplets caused by homozygosity or double hereozygosity for
      a mutation in the multimerization part of VWF gene. Autosomal dominant type 2D is
      rare and characterized by the lack of high molecular weight multimers and the
      presence of a characteristic intervening subband between individual oligimers due
      to mutation in the dimerization part of the VWF gene. In VWD type 2E, the large
      VWF multimers are missing and the pattern of the individual multimers shows only
      one clearly identifiable band, and there is no intervening band and no marked
      increase in the smallest oligomer. 2E appears to be less well defined, is usually
      autosomal dominant, and accounts for about one third of patients with 2A in a
      large cohort of VWD patients.

PMID- 17000886
TI  - Low frequency of phlebographic deep vein thrombosis after laparoscopic
      cholecystectomy--a pilot study.
AB  - To investigate the rate of deep vein thrombosis (DVT) after laparoscopic surgery,
      50 patients underwent bilateral phlebography 7-11 days after laparoscopic
      cholecystectomy (LC). All received thromboembolism prophylaxis, either low
      molecular weight heparin (LMWH) or dextran. Three patients were converted to open
      cholecystectomy. D-dimer was investigated preoperatively, on day 1 and on the day
      of phlebography. One asymptomatic DVT was found. One phlebogram was incomplete.
      Seven phlebograms were not optimal but of sufficient quality to rule out DVT. The
      frequency of DVT was thus 1 of 49 or 2.0% (95% confidence interval, 0-6.0%). No
      anticoagulants were prescribed after discharge. No patient developed late
      thromboembolic complications. D-dimer values increased significantly at day 1 and
      were further increased at the time of phlebography. The frequency of
      phlebographical DVTs thus seems to be low despite prophylaxis of questionable
      efficacy. The D-dimer values, however, suggest that the effects of LC on
      coagulation/fibrinolysis have a duration of longer than 1 week.

PMID- 17000887
TI  - Stromelysin-1 5A/6A and eNOS T-786C polymorphisms, MTHFR C677T and A1298C
      mutations, and cigarette-cannabis smoking: a pilot, hypothesis-generating study
      of gene-environment pathophysiological associations with Buerger's disease.
AB  - Buerger's disease (BD) etiologies are poorly understood. Beyond smoking
      cessation, medical-surgical treatments have limited success. We hypothesized that
      mutations associated with arterial vasospasm (stromelysin-1 5A/6A, eNOS T-786C)
      and C677T-A1298C methylene tetrahydrofolate reductase (MTHFR) interacted with
      cigarette-cannabis smoking, reducing vasodilatory nitric oxide (NO), promoting
      arterial spasm-thrombosis. Of 21 smoking BD patients (14 men [2 siblings], 7
      women; 20 white, 1 African-American), compared to 21 age-gender-race matched
      healthy controls, 5A/6A stromelysin- 1 homozygosity was present in 7 of 21 (33%)
      BD cases versus 5 of 21 (24%) controls (risk ratio 1.4; 95% confidence interval
      [CI] 0.5-3.7), and eNOS T-786C homozygosity was present in 3 of 21 (14%) BD cases
      versus 1 of 21 (5%) controls (risk ratio 3.0; 95% CI 0.3-26.6). C677T MTHFR
      homozygosity or compound C677T-A1298C heterozygosity was present in 7 of 21 cases
      (33%) versus 11 of 21 controls (52%) (risk ratio 0.6; 95% CI 0.3-1.3). In 18
      patients who stopped and 3 who continued smoking, all stromelysin-1 5A/6A and/or
      eNOS heterozygotes-homozygotes, superficial phlebitis, lower limb gangrenous
      ulcers, and intractable ischemic rest pain with arterial occlusion progressed
      despite conventional medical therapy, threatening amputation. In 15 patients, to
      increase vasodilatory NO via endothelial NO synthase, l-arginine (15 g/day) was
      given, along with folic acid (5 mg), vitamin B6 (100 mg), and B12 (2000 mg/day)
      to optimize homocysteine metabolism and reduce asymmetric dimethylarginine, a NO
      synthase inhibitor. Unexpectedly quickly and strikingly, within 8 weeks to 8
      months receiving l-arginine-folic acid, 11 of 15 treated patients improved with
      uniform pain reduction, ulcer healing, and in 5, full recovery of previously
      absent peripheral pulses. In smokers homo/heterozygous for stromelysin-1 5A/6A
      and eNOS T-786C mutations, we speculate that the development and severity of BD
      are related to a gene-environment vasospastic interaction with reduced NO
      mediated vasodilatation. Increasing NO production by l-arginine while optimizing
      homocysteine metabolism by folic acid-B6-B12 may have therapeutic benefit.
      Further blinded, placebo-controlled studies are needed to determine whether our
      observations can be generalized to larger BD cohorts.

PMID- 17000888
TI  - Control of edema in hypertensive subjects treated with calcium antagonist
      (nifedipine) or angiotensin-converting enzyme inhibitors with Pycnogenol.
AB  - The presence of edema in different phases and stages of essential hypertension
      may be due to antihypertensive treatment. Some drugs may cause edema by inducing
      vasodilatation, increasing the capillary exchange surface and capillary
      filtration. Pycnogenol has an important anti-edema effect in diabetic
      microangiopathy and chronic venous insufficiency. This 8-week study evaluated
      capillary filtration in 2 comparable treatment groups with hypertension treated
      with a calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitor
      to define its efficacy in preventing edema caused by antihypertensives. A
      significant decrease in filtration was observed in the Pycnogenol groups.
      Pycnogenol controls this type of edema, it helps to prevent and limit long-term
      damage in the microcirculation in hypertensive patients, and allows the dose of
      anti-hypertensive drugs to be reduced in most patients.

PMID- 17000889
TI  - The use of a surgical patch coated with human coagulation factors in surgical
      routine: a multicenter postauthorization surveillance.
AB  - Local hemostyptic agents are of great value to significantly reduce bleeding
      complications and various devices have become available for clinical use. The aim
      of this multicenter postauthorization surveillance was to study the surgeons'
      expectations regarding efficacy and safety of the surgical patch coated with
      human coagulation factors (TachoSil) under routine clinical conditions. A total
      of 408 patients had been included in this trial and the patients had to have an
      expected increased bleeding risk either due to patient related hemorrhagic risk
      factors or operations associated with an expected increase of bleeding
      complications. The main types of surgical interventions were operations on the
      liver (26%), vascular system (16%), gastrointestinal tract (10%), heart (8%),
      kidney (7%), thorax (7%), spleen (4%), and pancreas (4%). Other operations (18%)
      were reported in the fields of neurosurgery, urology, gynecology, dermatology,
      and on the thyroid gland. Based on subjective assessments the results have shown
      that TachoSil has met the surgeons' expectations to be efficacious and safe as a
      hemostatic treatment in a broad variety of surgical interventions. The observed
      benefits far exceed the frequencies of complications and many of the observed
      benefits easily translate into cost savings. In almost 50% of the cases the
      surgeons thought that the use of the topical hemostat TachoSil may have led to
      savings in blood component therapy. The savings of intra- and postoperative
      transfusions may lead to less frequent transfusion-related adverse effects and
      the lower probability of postoperative complications is of clinical importance.
      In particular, it is worth mentioning that based on the surgeons' assessment, the
      use of TachoSil may have helped to save the organ in 17% of the cases. Thus,
      these clinically relevant benefits may offer opportunities for improvements of
      hemostasis in patients at risk for bleeding complications and may facilitate the
      management of excessive bleeding.

PMID- 17000890
TI  - Circulated activated platelets and increased platelet reactivity in patients with
      Behcet's disease.
AB  - Behcet's disease (BD) is a multisystem disorder. Venous as well as arterial
      thrombosis is a common complication of BD but exact pathogenetic mechanism of the
      thrombotic tendency is not well known. This study aimed to evaluate circulating
      activated platelets and platelet reactivity in Behcet's patients. Twenty-two
      Behcet's patients (4 female, 18 male; mean age 38.6 +/- 10.9 years) and 20
      control subjects (8 female, 12 male; mean age 38.8 +/- 9.4 years) were included.
      Those patients who had hypertension, hyperlipidemia, peripheral or coronary
      artery disease, hepatic or renal function abnormality, and who were using aspirin
      and other platelet-active drugs were excluded. Platelet activity and reactivity
      to adenosine diphosphate (ADP) were measured by whole blood flow cytometry. We
      assessed markers of platelet degranulation (P-selectin; CD62P) and the activated
      glycoprotein IIb/IIIa receptor (PAC1 binding to fibrinogen binding site) before
      and after stimulation with ADP. Platelet P-selectin expression was not
      significantly different between patients and control subjects both at baseline
      (p=0.420) and after stimulation (p=0.56). Baseline (p=0.001) and ADP-stimulated
      (p=0.003) PAC1 binding was significantly higher in Behcet's patients than in the
      control group. Clinical activity has no effect on P-selectin expression and PAC1
      binding. There is evidence of platelet activity and hyperreactivity in patients
      with BD and this may contribute to a prothrombotic state. In addition to aspirin,
      other antiplatelet drugs may be useful in the prevention and treatment of
      thrombosis in Behcet's patients.

PMID- 17000891
TI  - Unfractionated heparin reduces the anti-platelet effects of abciximab but not
      eptifibatide during PCI.
AB  - In 29 patients undergoing percutaneous coronary intervention (PCI), we obtained
      blood samples at baseline, 10 minutes after standard weight-based abciximab
      (n=15) or double-bolus eptifibatide (n=14) and 5 minutes after unfractionated
      heparin (UFH; 70 U/kg bolus). The median percent inhibition was significantly
      higher in the eptifibatide group compared with the abciximab group both before
      (96.5% [94-100] vs. 85% [77-89.5] [adenosine diphosphate; ADP]; 89.5% [84-95] vs.
      59% [37.5-76.5] [thrombin receptor agonist peptide; TRAP], p<0.001 for both) and
      after UFH (95% [93-100] vs. 79% [68.8-87.5] [ADP]; 82% [77-93] vs. 51% [34.5
      71.3] [TRAP], p<0.001 for both). Addition of UFH significantly reduced platelet
      inhibition in the abciximab group (85% [77-89.5] vs. 79% [68.8-87.5] [ADP]; 59%
      [37.5-76.5] vs. 51% [34.5-71.3] [TRAP], p<0.05 for both) but not in the
      eptifibatide group (96.5% [94-100] vs. 95% [93-100] [ADP]; 89.5% [84-95] vs. 82%
      [77-93] [TRAP], p=ns for both). Eptifibatide achieved superior platelet
      inhibition before but especially after UFH compared with abciximab.

PMID- 17000892
TI  - Cbfa-1 (Runx-2) and osteocalcin expression by human osteoblasts in heparin
      osteoporosis in vitro.
AB  - Heparin may cause adverse effects on bone formation following long-term
      application. The exact pathomechanism is unclear, but in vitro data suggest an
      impaired osteoblast function. The transcription axis of Cbfa-1 (Runx-2) and
      osteocalcin is crucial in maintaining an equilibrium of bone formation and
      resorption in vivo. We used a human osteoblast cell culture model to further
      investigate the effect of heparin (low-molecular-weight heparin, dalteparin) on
      the expression of these two regulators of osteoblast differentiation. At high
      doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1
      expression in vitro. Our data support the hypothesis of a direct inhibition of
      osteoblast function underlying heparin osteoporosis.

PMID- 17000893
TI  - Estimated annual costs of prophylaxis and treatment of venous thromboembolic
      events associated with major orthopedic surgery in France.
AB  - Venous Thromboembolism (VTE) remains a major complication following orthopedic
      surgery despite heparin prophylaxis. Clinical consequences associated with this
      complication are deep vein thrombosis (DVT), pulmonary embolism, and long-term
      consequences of DVT, especially Postthrombotic syndrome (PTS). The purpose of the
      present study was to estimate the annual direct costs of VTE following major
      orthopedic surgery of the lower limb in France. This cost of illness study was
      performed by using available information from health system databases (1999) and
      literature and specific surveys (2002). Direct costs were calculated by using
      estimates of the number of patients with major orthopedic surgery in France
      during one year. Patients presenting with VTE were identified from the national
      disease-related group inpatient database. Additional resource consumption was
      identified by comparison with disease-related groups without the VTE
      complications. Ambulatory care costs after hospitalization, for recurrences and
      PTS, were estimated from specific surveys of general practitioners and venous
      disease specialists. Total annual costs of VTE associated with major orthopedic
      surgery for the French Sickness Fund were estimated to be approximately 60
      million euros over 1 year with 28 million euros for inpatient care and 30 million
      euros for recurrences and PTS.

PMID- 17000894
TI  - Spectrum of bleeding in acquired factor V inhibitor: a summary of 33 cases.
AB  - Coagulation factor V (FV) is an essential component of the prothrombinase
      complex, which activates the zymogen prothrombin to thrombin. Acquired FV
      inhibitor is rare and clinical symptoms are quite variable. The aim of this study
      was to summarize the spectrum of the bleeding presentation of acquired FV
      deficiency and characterize the underlying causes of the clinical symptoms. This
      study was designed as a descriptive retrospective and 30 case reports were
      included for further analysis. At least 33 cases of acquired FV inhibitor were
      investigated. Most patients have a presentation of bleeding and most of those are
      from hematuria and bleeding at surgical sites. Seven cases of asymptomatic
      acquired FV inhibitor were also detected. A total of 39.4% (19 of 33) of those
      cases with acquired FV inhibitor have an unknown cause. For those with known
      etiologies, chemical and drug-induced causes are the most common (30.8%).

PMID- 17000895
TI  - Chronic refractory idiopathic thrombocytopenic purpura (ITP) and anti-CD20
      monoclonal antibody: a case report.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder
      characterized by accelerated and premature destruction of platelets by
      reticuloendothelial system. CD20, a trans-membrane B-cell-specific antigen, is a
      potential target for treatment of certain malignant and nonmalignant plasma cell
      disorders including refractory ITP. Rituximab is a genetically engineered human
      anti-CD20 monoclonal antibody, which is approved for the treatment of low-grade
      non-Hodgkin's lymphoma. Recent clinical reports suggest that rituximab may be
      useful in treating certain patients with chronic refractory ITP. A 59-year-old
      woman with refractory ITP was placed on rituximab (four weekly doses of 375
      mg/m(2)) and her condition and platelet count were observed for 18 months. There
      was a gradual increase in platelet count and she was symptom free in this period
      and no side effects of the drug were reported. Anti-CD20 antibodies are likely to
      be used in the treatment of refractory ITP cases, but further studies about
      treatment schedule and criteria for patient selection should be done.

PMID- 17000896
TI  - TGF-beta1 and endothelial/tissue injury with high-dose intravenous iron therapy
      in renal failure: evidence or perception?

PMID- 17000899
TI  - Human monocyte-derived dendritic cells express TLR9 and react directly to the CpG
      A oligonucleotide D19.
AB  - Oligodeoxynucleotides (ODNs) containing unmethylated CpG exhibit their
      immunostimulatory activities by binding to TLR. Here, we show that human monocyte
      derived dendritic cells (moDC) contain TLR9 protein, surprisingly, in amounts
      comparable with plasmacytoid DC (pDC). Immature moDC but not mature moDC nor
      monocytes captured CpG-ODNs. moDC stimulation with the CpG-A ODN D19 up-regulated
      CD83, CD86, and HLA-DR. Without CD40 ligand costimulation, full maturation was
      not achieved. D19-stimulated moDC primed allogeneic CD4(+)-T cells for
      proliferation and differentiation into IFN-gamma-secreting Th1 cells. Neither IL
      12 nor IL-6 or TNF-alpha was involved. Microarray analysis pointed to a
      participation of Type I IFNs. In fact, D19-stimulated moDC secreted considerable
      amounts of IFN-alpha. This indicates that moDC themselves sense viral and
      bacterial DNA and do not need help from pDC.

PMID- 17000900
TI  - Inhibitors of DNA methylation and histone deacetylation independently relieve
      AML1/ETO-mediated lysozyme repression.
AB  - The human lysozyme (LZM) gene is highly methylated in LZM-nonexpressor immature
      myeloid and in nonmyeloid cells and unmethylated only in LZM-expressing cells.
      Extended methylation analyses of the CpG-poor 5' flanking region and of the exon
      4 CpG island (both containing Alu elements) of the LZM gene were now performed.
      Marked demethylation was noted after treatment of AML1/ETO-positive Kasumi-1
      cells with the DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5
      azaCdR), not associated with cellular differentiation. LZM mRNA in Kasumi-1, but
      not in several AML1/ETO-negative myeloid cell lines, was specifically and
      independently up-regulated upon treatment with 5-azaCdR and, to a lesser extent,
      with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA). Increased
      chromatin accessibility within the 5' LZM gene was observed concomitantly with 5
      azaCdR-induced demethylation. In contrast, TSA treatment had no effect on
      chromatin accessibility, but, as shown by chromatin immunoprecipitation, resulted
      in increased acetylation of histones H3 and H4. Repression of LZM transcription
      is mediated by conditional AML1/ETO expression in an inducible cell line model (U
      937), and is reversed by siRNA "knock-down" of AML1/ETO in Kasumi-1 cells (Dunne
      et al., Oncogene 25: 2006). Antagonization of LZM repression following
      conditional expression of AML1/ETO was achieved by TSA. In conclusion, we
      demonstrate complex interactions between DNA methylation and histone
      modifications in mediating LZM repression, which implicate AML1/ETO as one
      component involved in local chromatin remodeling. Interestingly, inhibitors of
      DNMTs and HDACs independently relieve repression of this CpG-poor gene in
      AML1/ETO-positive cells.

PMID- 17000902
TI  - The global structures of a wild-type and poorly functional plant luteoviral mRNA
      pseudoknot are essentially identical.
AB  - The helical junction region of a -1 frameshift stimulating hairpin-type mRNA
      pseudoknot from sugarcane yellow leaf virus (ScYLV) is characterized by a novel
      C27.(G7-C14) loop 2-stem 1 minor groove base triple, which is stacked on a
      C8+.(G12-C28) loop 1-stem 2 major groove base triple. Substitution of C27 with
      adenosine reduces frameshifting efficiency to a level just twofold above the slip
      site alone. Here, we show that the global structure of the C27A ScYLV RNA is
      nearly indistinguishable from the wild-type counterpart, despite the fact that
      the helical junction region is altered and incorporates the anticipated
      isostructural A27.(G7-C14) minor groove base triple. This interaction mediates a
      2.3-A displacement of C8+ driven by an A27 N6-C8+ O2 hydrogen bond as part of an
      A(n-1).C+.G-Cn base quadruple. The helical junction regions of the C27A ScYLV and
      the beet western yellows virus (BWYV) pseudoknots are essentially superimposable,
      the latter of which contains an analogous A25.(G7-C14) minor groove base triple.
      These results reveal that the global ground-state structure is not strongly
      correlated with frameshift stimulation and point to a reduced thermodynamic
      stability and/or enhanced kinetic lability that derives from an altered helical
      junction architecture in the C27A ScYLV RNA as a significant determinant for
      setting frameshifting efficiencies in plant luteoviral mRNA pseudoknots.

PMID- 17000901
TI  - The solution structure of REF2-I reveals interdomain interactions and regions
      involved in binding mRNA export factors and RNA.
AB  - The RNA binding and export factor (REF) family of mRNA export adaptors are found
      in several nuclear protein complexes including the spliceosome, TREX, and exon
      junction complexes. They bind RNA, interact with the helicase UAP56/DDX39, and
      are thought to bridge the interaction between the export factor TAP/NXF1 and
      mRNA. REF2-I consists of three domains, with the RNA recognition motif (RRM)
      domain positioned in the middle. Here we dissect the interdomain interactions of
      REF2-I and present the solution structure of a functionally competent double
      domain (NM; residues 1-155). The N-terminal domain comprises a transient helix (N
      helix) linked to the RRM by a flexible arm that includes an Arg-rich region. The
      N-helix, which is required for REF2-I function in vivo, overlaps the highly
      conserved REF-N motif and, together with the adjacent Arg-rich region, interacts
      transiently with the RRM. RNA interacts with REF2-I through arginine-rich regions
      in its N- and C-terminal domains, but we show that it also interacts weakly with
      the RRM. The mode of interaction is unusual for an RRM since it involves loops L1
      and L5. NMR signal mapping and biochemical analysis with NM indicate that DDX39
      and TAP interact with both the N and RRM domains of REF2-I and show that binding
      of these proteins and RNA will favor an open conformation for the two domains.
      The proximity of the RNA, TAP, and DDX39 binding sites on REF2-I suggests their
      binding may be mutually exclusive, which would lead to successive ligand binding
      events in the course of mRNA export.

PMID- 17000903
TI  - RNA aptamers binding the double-stranded RNA-binding domain.
AB  - Specific RNA recognition of proteins containing the double-strand RNA-binding
      domain (dsRBD) is essential for several biological pathways such as ADAR-mediated
      adenosine deamination, localization of RNAs by Staufen, or RNA cleavage by RNAse
      III. Structural analysis has demonstrated the lack of base-specific interactions
      of dsRBDs with either a perfect RNA duplex or an RNA hairpin. We therefore asked
      whether in vitro selections performed in parallel with individual dsRBDs could
      yield RNAs that are specifically recognized by the dsRBD on which they were
      selected . To this end, SELEX experiments were performed using either the second
      dsRBD of the RNA-editing enzyme ADAR1 or the second dsRBD of Xlrbpa, a homolog of
      TRBP that is involved in RISC formation. Several RNA families with high binding
      capacities for dsRBDs were isolated from either SELEX experiment, but no
      discrimination of these RNAs by different dsRBDs could be detected. The selected
      RNAs are highly structured, and binding regions map to two neighboring stem-loops
      that presumably form stacked helices and are interrupted by mismatches and
      bulges. Despite the lack of selective binding of SELEX RNAs to individual dsRBDS,
      selected RNAs can efficiently interfere with RNA editing in vivo.

PMID- 17000904
TI  - Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory
      activation of cells in atherosclerosis.
AB  - BACKGROUND: Noninvasive imaging of adhesion molecules such as vascular cell
      adhesion molecule-1 (VCAM-1) may identify early stages of inflammation in
      atherosclerosis. We hypothesized that a novel, second-generation VCAM-1-targeted
      agent with enhanced affinity had sufficient sensitivity to enable real-time
      detection of VCAM-1 expression in experimental atherosclerosis in vivo, to
      quantify pharmacotherapy-induced reductions in VCAM-1 expression, and to identify
      activated cells in human plaques. METHODS AND RESULTS: In vivo phage display in
      apolipoprotein E-deficient mice identified a linear peptide affinity ligand,
      VHPKQHR, homologous to very late antigen-4, a known ligand for VCAM-1. This
      peptide was developed into a multivalent agent detectable by MRI and optical
      imaging (denoted VINP-28 for VCAM-1 internalizing nanoparticle 28, with 20 times
      higher affinity than previously reported for VNP). In vitro, VINP-28 targeted all
      cell types expressing VCAM-1. In vivo, MRI and optical imaging in apolipoprotein
      E-deficient mice (n=28) after injection with VINP-28 or saline revealed signal
      enhancement in the aortic root of mice receiving VINP-28 (P<0.05). VINP-28
      colocalized with endothelial cells and other VCAM-1-expressing cells, eg,
      macrophages, and was spatially distinct compared with untargeted control
      nanoparticles. Atheromata of atorvastatin-treated mice showed reduced VINP-28
      deposition and VCAM-1 expression. VINP-28 enhanced early lesions in juvenile mice
      and resected human carotid artery plaques. CONCLUSIONS: VINP-28 allows
      noninvasive imaging of VCAM-1-expressing endothelial cells and macrophages in
      atherosclerosis and spatial monitoring of anti-VCAM-1 pharmacotherapy in vivo and
      identifies inflammatory cells in human atheromata. This clinically translatable
      agent could noninvasively detect inflammation in early, subclinical
      atherosclerosis.

PMID- 17000905
TI  - Systemic tumor necrosis factor-related apoptosis-inducing ligand delivery shows
      antiatherosclerotic activity in apolipoprotein E-null diabetic mice.
AB  - BACKGROUND: Although in vitro studies have suggested that tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) might be involved in vascular biology,
      its potential role in the pathogenesis and/or treatment of atherosclerosis has
      not been investigated. METHODS AND RESULTS: Both recombinant human TRAIL and an
      adeno-associated virus vector expressing human TRAIL were used to deliver TRAIL
      in apolipoprotein E (apoE)-null mice in which diabetes mellitus was induced by
      destruction of islet cells with streptozotocin. Diabetes in apoE-null mice was
      associated with a significant increase in atherosclerotic plaque area and
      complexity in the aorta as assessed by a marked increase in interstitial
      collagen, cellular proliferation, and macrophage infiltration and a focal loss of
      endothelial coverage. Repeated intraperitoneal injections of recombinant human
      TRAIL and a single intravenous injection of adeno-associated virus-human TRAIL
      significantly attenuated the development of atherosclerotic plaques in apoE-null
      animals. TRAIL also markedly affected the cellular composition of plaque lesions
      by inducing apoptosis of infiltrating macrophages and increasing the vascular
      smooth muscle cell content. Moreover, TRAIL promoted the in vitro migration of
      cultured human aortic vascular smooth muscle cells but not of monocytes or
      macrophages. Conversely, TRAIL selectively induced apoptosis of human cultured
      macrophages but not of vascular smooth muscle cells. CONCLUSIONS: Overall, data
      from the present study indicate that atherosclerosis in diabetic apoE-null mice
      is ameliorated by systemic TRAIL administration and that adeno-associated virus
      mediated TRAIL gene delivery might represent an innovative method for the therapy
      of diabetic vascular diseases.

PMID- 17000906
TI  - Dimethyl sulfoxide inhibits tissue factor expression, thrombus formation, and
      vascular smooth muscle cell activation: a potential treatment strategy for drug
      eluting stents.
AB  - BACKGROUND: Subacute stent thrombosis is a major clinical concern, and the search
      for new molecules to cover stents remains important. Dimethyl sulfoxide (DMSO) is
      used for preservation of hematopoietic progenitor cells and is infused into
      patients undergoing bone marrow transplantation. Despite its intravenous
      application, the impact of DMSO on vascular cells has not been assessed. METHODS
      AND RESULTS: In human endothelial cells, monocytes, and vascular smooth muscle
      cells (VSMC), DMSO inhibited tissue factor (TF) expression and activity in
      response to tumor necrosis factor-alpha or thrombin in a concentration-dependent
      manner. DMSO did not exert any toxic effects as assessed by phase-contrast
      microscopy, trypan blue exclusion, and lactate dehydrogenase release. Real-time
      polymerase chain reaction revealed that inhibition of TF expression occurred at
      the mRNA level. This effect was mediated by reduced activation of the mitogen
      activated protein kinases c-Jun terminal NH2 kinase (51+/-6%; P=0.0005) and p38
      (50+/-3%; P<0.0001) but not p44/42 (P=NS). In contrast to TF, DMSO did not affect
      expression of TF pathway inhibitor or plasminogen activator inhibitor-1. In vivo,
      DMSO treatment suppressed TF activity (41%; P<0.002) and prevented thrombotic
      occlusion in a mouse carotid artery photochemical injury model. DMSO also
      inhibited VSMC proliferation (70%; P=0.005) and migration (77%; P=0.0001) in a
      concentration-dependent manner; moreover, it prevented rapamycin and paclitaxel
      induced upregulation of TF expression. CONCLUSIONS: DMSO suppresses TF expression
      and activity, as well as thrombus formation; in addition, it inhibits VSMC
      proliferation and migration. Given its routine use in modern clinical practice,
      we propose DMSO as a novel strategy for coating drug-eluting stents and treating
      acute coronary syndromes.

PMID- 17000907
TI  - Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart
      disease in the Framingham Heart Study.
AB  - BACKGROUND: Bilirubin is an antioxidant that suppresses lipid oxidation and
      retards atherosclerosis formation. An inverse association between serum bilirubin
      and coronary heart disease has been reported. Linkage studies have identified a
      major locus at the chromosome 2q telomere that affects bilirubin concentrations.
      A candidate gene in the linkage region encodes hepatic bilirubin uridine
      diphosphate-glucuronosyltransferase (UGT1A1). The insertion of a TA in the TATAA
      box of the gene, an allele designated UGT1A1*28, decreases gene transcription.
      Individuals homozygous for UGT1A1*28 (genotype 7/7) have increased serum
      bilirubin levels compared with carriers of the 6 allele. To date, no significant
      association between UGT1A1*28 and cardiovascular disease (CVD) events has been
      reported. We performed an association study in the Framingham Heart Study
      population to investigate whether UGT1A1*28 is associated with the risk of CVD
      events. METHODS AND RESULTS: The study population included 1780 unrelated
      individuals from the Offspring cohort (49% males, mean age 36 years at entry) who
      had been followed up for 24 years. Individuals with genotype 7/7 had
      significantly higher bilirubin levels (mean+/-SD 1.14+/-0.44 mg/dL) than those
      with genotypes 6/6 and 6/7 (mean+/-SD 0.69+/-0.27 mg/dL, P<0.01). Using the Cox
      proportional hazards model, we found significant associations between the
      UGT1A1*28 allele and decreased risk of CVD. Individuals with genotype 7/7
      (population frequency of 11%) had approximately one third the risk for CVD and
      coronary heart disease as carriers of the 6 allele, which resulted in a hazard
      ratio (95% confidence interval) of 0.36 (0.18 to 0.74) and 0.30 (0.12 to 0.74),
      respectively. CONCLUSIONS: Homozygote UGT1A1*28 allele carriers with higher serum
      bilirubin concentrations exhibit a strong association with lower risk of CVD.

PMID- 17000908
TI  - Real-time 2-photon imaging of mitochondrial function in perfused rat hearts
      subjected to ischemia/reperfusion.
AB  - BACKGROUND: Mitochondria play pivotal roles in cell death; the loss of
      mitochondrial membrane potential (delta psi(m)) is the earliest event that
      commits the cell to death. Here, we report novel real-time imaging of delta
      psi(m) in individual cardiomyocytes within perfused rat hearts using 2-photon
      laser-scanning microscopy, which has unique advantages over conventional confocal
      microscopy: greater tissue penetration and lower tissue toxicity. METHODS AND
      RESULTS: The Langendorff-perfused rat heart was loaded with a fluorescent
      indicator of delta psi(m), tetramethylrhodamine ethyl ester. Tetramethylrhodamine
      ethyl ester was excited with an 810-nm line of a Ti:sapphire laser, and its
      fluorescence in the heart cells was successfully visualized up to approximately
      50 microm from the epicardial surface. Taking advantage of this system, we
      monitored the spatiotemporal changes of delta psi(m) in response to
      ischemia/reperfusion at the subcellular level. No-flow ischemia caused
      progressive delta psi(m) loss and a more prominent delta psi(m) loss on
      reperfusion. During ischemia/reperfusion, cells maintained a constant delta
      psi(m) for the cell-to-cell specific period of latency, followed by a rapid,
      complete, and irreversible delta psi(m) loss, and this process did not affect the
      neighboring cells. Within a cell, delta psi(m) loss was initiated in a particular
      area of mitochondria and rapidly propagated along the longitudinal axis. These
      spatiotemporal changes in delta psi(m) resulted in marked cellular and
      subcellular heterogeneity of mitochondrial function. Ischemic preconditioning
      reduced the number of cells undergoing delta psi(m) loss, whereas cyclosporin A
      partially inhibited delta psi(m) loss in each cell. CONCLUSIONS: Investigation of
      cellular responses in the natural environment will increase knowledge of
      ischemia/reperfusion injury and provide deeper insights into
      antiischemia/reperfusion therapy that targets mitochondria.

PMID- 17000909
TI  - Family history and the risk of sudden cardiac death as a manifestation of an
      acute coronary event.
AB  - BACKGROUND: Observational studies have suggested that a parental history of
      sudden death increases one's risk of dying suddenly. This study tested the
      hypothesis that a family history of sudden cardiac death (SCD) is a risk factor
      for SCD caused by an acute coronary event. METHODS AND RESULTS: A retrospective
      case-control study included (1) consecutive victims of SCD (n=138) whose deaths
      were verified to be due to an acute coronary event without a history of prior
      myocardial infarction at medicolegal autopsy, (2) consecutive patients surviving
      an acute myocardial infarction (AMI; n=254), and (3) healthy control subjects
      (n=470). Family history of AMI and SCD among the first-degree relatives was
      ascertained in each study group. The incidence of SCD in the 1223 first-degree
      relatives of SCD victims was higher (5.2%) than that in the 2326 relatives of AMI
      survivors (3.3%; odds ration [OR] 1.6, 95% confidence interval [CI] 1.2 to 2.2,
      P<0.01) or the 3748 relatives of controls (OR 2.2; 95% CI 1.6 to 3.0, P<0.001).
      The history of SCD in 2 or more first-degree relatives was also higher (10.9%)
      among SCD victims than among AMI survivors (3.5%; OR 3.3, 95% CI 1.4 to 7.8,
      P<0.01) or controls (1.1%; OR 11.3, 95% CI 4.0 to 31.8, P<0.001). The family
      history of AMI did not differ between the SCD and AMI groups. Male gender and
      current smoking were the only coronary risk factors that were more prevalent
      among SCD victims than among AMI survivors (P<0.001 for both). CONCLUSIONS:
      Subjects with a family history of SCD have an increased risk of dying suddenly
      during an acute coronary event.

PMID- 17000910
TI  - Randomized trial of atorvastatin for reduction of postoperative atrial
      fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3
      (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery)
      study.
AB  - BACKGROUND: Atrial fibrillation (AF) after cardiac surgery is associated with
      increased risk of complications, length of stay, and cost of care. Observational
      evidence suggests that patients who have undergone previous statin therapy have a
      lower incidence of postoperative AF. We tested this observation in a randomized,
      controlled trial. METHODS AND RESULTS: Two hundred patients undergoing elective
      cardiac surgery with cardiopulmonary bypass, without previous statin treatment or
      history of AF, were enrolled. Patients were randomized to atorvastatin (40 mg/d,
      n=101) or placebo (n=99) starting 7 days before operation. The primary end point
      was incidence of postoperative AF; secondary end points were length of stay, 30
      day major adverse cardiac and cerebrovascular events, and postoperative C
      reactive protein (CRP) variations. Atorvastatin significantly reduced the
      incidence of AF versus placebo (35% versus 57%, P=0.003). Accordingly, length of
      stay was longer in the placebo versus atorvastatin arm (6.9+/-1.4 versus 6.3+/
      1.2 days, P=0.001). Peak CRP levels were lower in patients without AF (P=0.01),
      irrespective of randomization assignment. Multivariable analysis showed that
      atorvastatin treatment conferred a 61% reduction in risk of AF (odds ratio 0.39,
      95% confidence interval 0.18 to 0.85, P=0.017), whereas high postoperative CRP
      levels were associated with increased risk (odds ratio 2.0, 95% confidence
      interval 1.2 to 7.0, P=0.01). The incidence of major adverse cardiac and
      cerebrovascular events at 30 days was similar in the 2 arms. CONCLUSIONS:
      Treatment with atorvastatin 40 mg/d, initiated 7 days before surgery,
      significantly reduces the incidence of postoperative AF after elective cardiac
      surgery with cardiopulmonary bypass and shortens hospital stay. These results may
      influence practice patterns with regard to adjuvant pharmacological therapy
      before cardiac surgery.

PMID- 17000911
TI  - Reduction in the incidence of acute myocardial infarction associated with a
      citywide smoking ordinance.
AB  - BACKGROUND: Secondhand smoke exposure increases the risk of acute myocardial
      infarction (AMI). One study (Helena, Mont) examined the issue and found a
      decrease in AMI associated with a smoke-free ordinance. We sought to determine
      the impact of a smoke-free ordinance on AMI admission rates in another
      geographically isolated community (Pueblo, Colo). METHODS AND RESULTS: We
      assessed AMI hospitalizations in Pueblo during a 3-year period, 1.5 years before
      and 1.5 years after implementation of a smoke-free ordinance. We compared the AMI
      hospitalization rates among individuals residing within city limits, the area
      where the ordinance applied, versus those outside city limits. We also compared
      AMI rates during this time period with another geographically isolated but
      proximal community, El Paso County, Colo, that did not have an ordinance. A total
      of 855 patients were hospitalized with a diagnosis of primary AMI in Pueblo
      between January 1, 2002, and December 31, 2004. A reduction in AMI
      hospitalizations was observed in the period after the ordinance among Pueblo city
      limit residents (relative risk [RR]=0.73, 95% confidence interval [CI] 0.63 to
      0.85). No significant changes in AMI rates were observed among residents outside
      city limits (RR=0.85, 95% CI 0.63 to 1.16) or in El Paso County during the same
      period (RR=0.97, 95% CI 0.89 to 1.06). The reduction in AMI rate within Pueblo
      differed significantly from changes in the external control group (El Paso
      County) even after adjustment for seasonal trends (P<0.001). CONCLUSIONS: A
      public ordinance reducing exposure to secondhand smoke was associated with a
      decrease in AMI hospitalizations in Pueblo, Colo, which supports previous data
      from a smaller study.

PMID- 17000912
TI  - Relationship between postoperative cardiac troponin I levels and outcome of
      cardiac surgery.
AB  - BACKGROUND: Cardiac surgery may be associated with significant perioperative and
      postoperative morbidity and mortality. Underlying pathology, surgical technique,
      and postoperative complications may all influence outcome. These factors may be
      reflected as a rise in postoperative troponin levels. Interpretation of troponin
      levels in this setting may therefore be complex. This study assessed the
      prognostic significance of such measurements, taking into account potential
      confounding variables. METHODS AND RESULTS: One-thousand three hundred sixty-five
      patients undergoing cardiac surgery underwent measurement of cardiac troponin I
      (cTnI) at 2 and 24 hours after surgery. The relationship of these measurements to
      subsequent mortality was established. After taking into account all other
      variables, cTnI levels measured at 24 hours were independently predictive of
      mortality at 30 days (odds ratio [OR] 1.14 per 10 microg/L, 95% confidence
      interval [CI] 1.05 to 1.24, P=0.002), 1 year (OR 1.10 per 10 microg/L, 95% CI
      1.03 to 1.18, P=0.006), and 3 years (OR 1.07 per 10 microg/L, 95% CI 1.00 to
      1.15, P=0.04). Cardiac TnI levels in the highest quartile at 24 hours were
      associated with a particularly poor outcome. CONCLUSIONS: cTnI levels measured 24
      hours after cardiac surgery predict short-, medium-, and long-term mortality and
      remain independently predictive when adjusted for all other potentially
      confounding variables, including operation complexity.

PMID- 17000913
TI  - Images in cardiovascular medicine. Giant compressive aneurysm of the left auricle
      in a 1-day-old neonate.

PMID- 17000914
TI  - Images in cardiovascular medicine. The case of a disappearing left atrial
      appendage thrombus: direct visualization of left atrial thrombus migration,
      captured by echocardiography, in a patient with atrial fibrillation, resulting in
      a stroke.

PMID- 17000915
TI  - Images in cardiovascular medicine. Directly to the heart.

PMID- 17000916
TI  - Letter by Thalhammer et al regarding article, "External carotid artery-internal
      jugular vein fistula: a complication of internal jugular cannulation".

PMID- 17000917
TI  - Pulmonary hypertension: deserving of attention.

PMID- 17000918
TI  - Small-molecule glycoprotein IIb/IIIa antagonists and bleeding risk in women: too
      much of a good thing?

PMID- 17000919
TI  - Low-level environmental exposure to lead unmasked as silent killer.

PMID- 17000920
TI  - Endothelin-1 and the pulmonary vascular response to altitude: a new therapeutic
      target?

PMID- 17000921
TI  - Pulmonary arterial hypertension.

PMID- 17000922
TI  - Positive association between plasma fibrinogen level and incident hypertension
      among men: population-based cohort study.
AB  - Elevated plasma fibrinogen is implicated in cardiovascular disease. However, it
      is not clear whether fibrinogen levels predict the development of hypertension.
      We examined the relationship between plasma fibrinogen level and hypertension in
      a population-based cohort study of 3654 participants (mean age: 61.5 years;
      range: 49 to 84 years) at the baseline examination (1992-1994) in the Blue
      Mountains region, west of Sydney, Australia, who were examined 5 years (1997
      1999) later. Main outcomes of interest were prevalent hypertension (systolic
      blood pressure >or=140 mm Hg, diastolic blood pressure >or=90 mm Hg, or a
      combination of self-reported hypertension diagnosis and use of antihypertensive
      medications) at baseline (n=2212/3180) and 5-year incidence of hypertension among
      baseline normotensive individuals (n=361/637). Elevated plasma fibrinogen level
      was positively associated with prevalent hypertension both among men and women
      and positively associated with 5-year incident hypertension among men,
      independent of several cardiovascular risk factors. Multivariable odds ratio (95%
      CI) of 5-year incident hypertension comparing tertile 3 of plasma fibrinogen
      (>or=3.9 g/L) with tertile 1 (<or=3.2 g/L) was 1.95 (1.03 to 3.68; P
      trend=0.040). This prospective association, however, was not observed in women
      (odds ratio; 95% CI) comparing tertile 3 versus tertile 1 of plasma fibrinogen
      (1.00; 0.54 to 1.86; P trend=0.986). Subgroup analyses stratified by smoking,
      body mass index, diabetes, and blood pressure categories supported this male
      gender-specific pattern of association. These data provide prospective
      epidemiological evidence of an essential link between plasma fibrinogen level and
      incident hypertension among men but not among women, a finding consistent with
      that observed in the Atherosclerosis Risk in Communities Study.

PMID- 17000923
TI  - Importance of salt in determining blood pressure in children: meta-analysis of
      controlled trials.
AB  - To assess the effect of reducing salt intake on blood pressure in children, we
      carried out a meta-analysis of controlled trials. Trials were included if
      participants were children (< or = 18 years), and duration of salt reduction must
      have been for > or = 2 weeks. Mean effect size was calculated using a fixed
      effect model, because there was no significant heterogeneity. Ten trials of
      children and adolescents with 966 participants were included (median age: 13
      years; range: 8 to 16 years; median duration: 4 weeks; range: 2 weeks to 3
      years). Salt intake was reduced by 42% (interquartile range [IQR]: 7% to 58%).
      There were significant reductions in blood pressure: systolic: -1.17 mm Hg (95%
      CI: -1.78 to -0.56 mm Hg; P<0.001); diastolic: -1.29 mm Hg (95% CI: -1.94 to 
      0.65 mm Hg; P<0.0001). Three trials of infants with 551 participants were
      included (median duration: 20 weeks; range: 8 weeks to 6 months). Salt intake was
      reduced by 54% (IQR: 51% to 79%). There was a significant reduction in systolic
      blood pressure: -2.47 mm Hg (95% CI: -4.00 to -0.94 mm Hg; P<0.01). This is the
      first meta-analysis of salt reduction in children, and it demonstrates that a
      modest reduction in salt intake causes immediate falls in blood pressure and, if
      continued, may well lessen the subsequent rise in blood pressure with age. This
      would result in major reductions in cardiovascular disease. These results in
      conjunction with other evidence provide strong support for a reduction in salt
      intake in children.

PMID- 17000924
TI  - Renal function in primary aldosteronism.

PMID- 17000926
TI  - A new hormone therapy with drospirenone and NO production in postmenopausal
      women.

PMID- 17000927
TI  - Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin
      converting enzyme 2, and neprilysin in a family study.
AB  - The renin-angiotensin system is a key regulator of blood pressure (BP), with
      inhibitors of angiotensin-converting enzyme (ACE) used clinically to treat
      hypertension and other cardiovascular conditions. ACE2 is a newly identified
      member of this system, which converts angiotensin II to angiotensin, and of which
      the occurrence in plasma has not been investigated. The aim of this study was to
      determine the heritability of circulating ACE, ACE2, and neprilysin (NEP), which
      may also be a regulator of BP, in a family study, and to determine covariates
      that contribute to the variation in plasma activity. ACE, ACE2, and NEP
      activities were measured in plasma from 534 subjects in the Leeds Family Study
      using selective fluorogenic substrates. Genetic factors accounted for 24.5%, 67%,
      and 22.7% of the phenotypic variation in circulating ACE, ACE2, and NEP,
      respectively. ACE insertion/deletion polymorphism and other measured covariates
      accounted for 23.8% of variance in circulating ACE. High-density lipoprotein
      cholesterol was a significant determinant of circulating ACE2. Measured
      covariates accounted for 17.3% of variation in circulating NEP. ACE and NEP were
      associated with systolic and diastolic BP in univariate analyses; however, only
      ACE was independently associated with systolic and diastolic BP after accounting
      for covariates and shared childhood household.

PMID- 17000928
TI  - Angiotensin II stimulates endothelial NO synthase phosphorylation in thoracic
      aorta of mice with abdominal aortic banding via type 2 receptor.
AB  - Abdominal aortic banding in mice induces upregulation of angiotensin II (Ang II)
      type 2 (AT2) receptors in the pressure-overloaded thoracic aorta. To clarify
      mechanisms underlying the vascular AT2 receptor-dependent NO production, we
      measured aortic levels of endothelial NO synthase (eNOS), eNOS phosphorylated at
      Ser633 and Ser1177, protein kinase B (Akt), and Akt phosphorylated at Ser473 in
      thoracic aortas of mice after banding. Total eNOS, both forms of phosphorylated
      eNOS, Akt, and phosphorylated Akt levels, as well as cGMP contents, were
      significantly increased 4 days after banding. The administration of PD123319 (an
      AT2 receptor antagonist) or icatibant (a bradykinin B2 receptor antagonist)
      abolished the banding-induced upregulation of both forms of phosphorylated eNOS,
      as well as elevation of cGMP, but did not affect the upregulation of eNOS, Akt,
      and phosphorylated Akt. In the in vitro experiments using aortic rings prepared
      from banded mice, Ang II produced significant increases in both forms of
      phosphorylated eNOS, as well as cGMP, and these effects were blocked by PD123319
      and icatibant. Ang II-induced eNOS phosphorylation and cGMP elevation in aortic
      rings were inhibited by protein kinase A (PKA) inhibitors H89 and KT5720 but not
      by phosphatidylinositol 3-kinase inhibitors wortmannin and LY24002. The
      contractile response to Ang II was attenuated in aortic rings from banded mice
      via AT2 receptor, and this attenuation was blocked by PKA inhibitors. These
      results suggest that the activation of AT2 receptor by Ang II induces
      phosphorylation of eNOS at Ser633 and Ser1177 via a PKA-mediated signaling
      pathway, resulting in sustained activation of eNOS.

PMID- 17000929
TI  - Genome-wide scan for premature hypertension supports linkage to chromosome 2 in a
      large Kyrgyz family.
AB  - We report a genome-wide scan for susceptibility loci to hypertension in a single
      Kyrgyz family where 10 of the affected relatives developed hypertension before
      the age of 35 years, and some members have suffered stroke. The early onset of
      disease and the geographic isolation of the Kyrgyz population are both expected
      to select for an increased influence of genetic factors in hypertension. We
      genotyped 44 individuals from this Krygyz family with 374 microsatellite markers,
      covering a 10-centimorgan map. Nonparametric analysis suggests that affected
      status is linked to loci in the chromosome 2q23 to q37 genomic interval, whereas
      2-point parametric analysis returned a logarithm of odds score of 2.67 for marker
      D2S2330 (2q24.3). Multipoint linkage analysis substantiated the evidence for a
      hypertension susceptibility allele in the chromosome 2q23 to q36 region. Fine
      mapping and haplotype analysis implicate that the genetic lesion resides between
      markers D2S2380 (166.5 cM) and D2S335 (175.9 cM). This finding supports other
      recent studies of early onset hypertension suggesting that the region 2q24.3 to
      q31.1 encompasses a novel locus for premature hypertension.

PMID- 17000930
TI  - Predictors of angiotensin-converting enzyme inhibitor-induced reduction of
      urinary albumin excretion in nondiabetic patients.
AB  - Urinary albumin excretion is a predictor for cardiovascular mortality and
      morbidity. We investigated which parameters determine baseline urinary albumin
      excretion in nondiabetic subjects, without renal disease. In addition, we
      evaluated the parameters that predict the albuminuria-lowering efficacy of an
      angiotensin-converting enzyme inhibitor. In this substudy of the Prevention of
      Renal and Vascular Endstage Disease Intervention Trial, 384 microalbuminuric
      patients were included. Patient and biochemical characteristics were obtained at
      baseline and after 3 months of double-blinded, randomized treatment (fosinopril
      20 mg or placebo). Mean age was 51.1+/-11.5 years, and 65.6% were male. Median
      urinary albumin excretion was 22.2 mg per 24 hours. At baseline, mean arterial
      pressure (beta(standardized)=0.161; P=0.006), urinary sodium excretion
      (beta(standardized)=0.154; P=0.011), and estimated renal function were
      independently associated with albumin excretion. In these predominantly
      normotensive to prehypertensive subjects, fosinopril reduced albumin excretion by
      18.5% versus a 6.1% increase on placebo after 3 months (P<0.001). Fosinopril use
      and blood pressure reduction independently predicted the change in urinary
      albumin excretion. Baseline urinary albumin excretion independently predicted the
      antialbuminuric effect of fosinopril (beta(standardized)=-0.303; P<0.001). In
      conclusion, at baseline, sodium intake and blood pressure were positively
      associated with urinary albumin excretion. Fosinopril reduced albuminuria more
      than might be expected from its blood pressure-lowering effect alone, and this
      effect was more outspoken in subjects with higher baseline albumin excretion.
      Based on our data, we hypothesize that angiotensin-converting enzyme inhibition
      may result in superior cardiovascular protection when compared with other blood
      pressure-lowering agents in subjects with higher baseline levels of albuminuria.

PMID- 17000931
TI  - Chronic low-dose angiotensin II infusion increases venomotor tone by neurogenic
      mechanisms.
AB  - The purpose of this study was to identify changes in venomotor tone in the
      chronic low-dose angiotensin II (Ang II) model of hypertension and to establish
      the contribution of sympathetic nerve activation to these venomotor tone changes.
      Male Sprague-Dawley rats were acclimatized to a 0.4% or 2.0% NaCl diet for 7 days
      and then catheterized to allow chronic and repeated measures of arterial
      pressure, central venous pressure, and mean circulatory filling pressure (MCFP),
      an index of venous smooth muscle tone, in conscious undisturbed rats. After 4
      days of recovery and a 3-day control period, an Ang II or physiological saline
      filled osmotic minipump was implanted subcutaneously to deliver Ang II (150 ng/kg
      per minute) or vehicle control for 14 days. MCFP was measured in duplicate before
      and after acute ganglionic blockade with hexamethonium (30 mg/kg i.v.) on control
      day 2 and Ang II infusion on days 1, 3, 7, and 14. Blood volume was also measured
      on these days and was unchanged for the duration of the study in all of the
      groups. Arterial pressure was increased for the duration of Ang II infusion in
      rats on both 0.4% and 2% NaCl diets, but the increase was significantly greater
      in the 2% NaCl group and completely abolished by hexamethonium. MCFP was
      significantly increased for the entire Ang II infusion period only in rats fed 2%
      NaCl, and this increase was completely abolished by hexamethonium. We conclude
      that the combination of chronic low-dose Ang II infusion and high dietary salt
      intake engages the sympathetic nervous system to increase venomotor tone.

PMID- 17000932
TI  - Mechanisms of sympathetic activation in obesity-related hypertension.

PMID- 17000933
TI  - Medroxyprogesterone acetate but not drospirenone ablates the protective function
      of 17 beta-estradiol in aldosterone salt-treated rats.
AB  - Controversial results obtained from human and animal studies on the prevention of
      heart disease by estrogens and progestins warrant a better understanding of
      nuclear hormone receptor function and interaction. To address this issue and
      taking into account that effects of synthetic progestins are not only referable
      to action through the progesterone receptor but may also be mediated by other
      steroid receptors, we characterized cardiovascular function and inflammatory gene
      expression in aldosterone salt-treated rats on long-term administration of 17beta
      estradiol, medroxyprogesterone acetate, and drospirenone, a new progestogen
      exhibiting antimineralocorticoid activity. The complex pattern of cardiovascular
      injury in ovariectomized Wistar rats induced by chronic aldosterone infusion plus
      a high-salt diet was significantly attenuated in sham-ovariectomized rats and by
      coadministration of 17beta-estradiol in ovariectomized animals after 8 weeks of
      continuous treatment. The beneficial role of 17beta-estradiol on blood pressure,
      cardiac hypertrophy, vascular osteopontin expression, perivascular fibrosis, and
      impaired NO-dependent relaxation of isolated aortic rings was completely
      abrogated by coadministration of medroxyprogesterone acetate. In contrast,
      drospirenone was either neutral or additive to 17beta-estradiol in protecting
      against aldosterone salt-induced cardiovascular injury and inflammation. The
      current results support the hypothesis of complex interactions among estrogen,
      progesterone, glucocorticoid, androgen, and mineralocorticoid receptor signaling
      in cardiovascular injury and inflammation. Novel progestins, such as
      drospirenone, confer superior effects compared with medroxyprogesterone acetate
      in a model of aldosterone-induced heart disease because of its
      antimineralocorticoid properties.

PMID- 17000934
TI  - Improving medication adherence: challenges for physicians, payers, and policy
      makers.

PMID- 17000935
TI  - Amyloidosis and the heart: a comprehensive review.
AB  - Infiltration of the heart from insoluble protein deposits in amyloidosis often
      results in restrictive cardiomyopathy that manifests late in its course with
      heart failure and conduction abnormalities. While the rare primary amyloidosis
      related heart disease has been well characterized, senile amyloidosis occurring
      in the seventh decade of life most frequently affects the heart. Early diagnosis
      of cardiac amyloidosis may improve outcomes but requires heightened suspicion and
      a systematic clinical approach to evaluation. Demonstration of tissue
      infiltration of biopsy specimens using special stains, followed by
      immunohistochemical studies and genetic testing, is essential in defining the
      specific protein involved. The therapeutic strategy depends on the
      characterization of the type of amyloid protein and extent of disease and may
      include chemotherapy, stem cell transplantation, and liver transplantation. Heart
      transplantation is controversial and is generally performed only at isolated
      centers.

PMID- 17000936
TI  - The effect of early, intensive statin therapy on acute coronary syndrome: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: In addition to well-established secondary prevention benefits for
      atherosclerotic coronary artery disease, 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitors (statins) are hypothesized to have short-term
      benefit in acute coronary syndrome (ACS), yet the data are inconsistent, with
      some trials underpowered to demonstrate therapeutic benefit. Our objective was to
      determine the effects of early, intensive statin therapy for ACS. DATA SOURCES:
      Studies found in the PubMed, MEDLINE, EMBASE, BIOSIS, SciSearch, PASCAL, and
      International Pharmaceutical Abstracts (IPA) databases and the Cochrane
      Controlled Trials Register published between January 1974 and May 2006. STUDY
      SELECTION: Randomized controlled trials of statins begun within 14 days of
      hospitalization for ACS were included. DATA EXTRACTION: Two investigators
      independently abstracted study quality, characteristics, and outcomes. DATA
      SYNTHESIS: Thirteen randomized controlled trials published before May 2006 were
      available, involving 17 963 adults (median number of patients, 135; median follow
      up, 6 months). Early, intensive statin therapy for ACS decreased the rate of
      death and cardiovascular events over 2 years of follow-up (hazard ratio, 0.81
      [95% confidence interval, 0.77-0.87]) (Q(3) = 58.54; P<.001; I(2) = 95%).
      Survival curves revealed that this benefit begins to occur between 4 and 12
      months, achieving statistical significance by 12 months. There was no evidence of
      publication bias, and sensitivity analyses did not identify a dominating study or
      study characteristic. CONCLUSIONS: Early, intensive statin therapy reduces death
      and cardiovascular events after 4 months of treatment. The validity of this
      finding would be strengthened by an analysis of individual patient data.

PMID- 17000937
TI  - The care transitions intervention: results of a randomized controlled trial.
AB  - BACKGROUND: Patients with complex care needs who require care across different
      health care settings are vulnerable to experiencing serious quality problems. A
      care transitions intervention designed to encourage patients and their caregivers
      to assert a more active role during care transitions may reduce rehospitalization
      rates. METHODS: Randomized controlled trial. Between September 1, 2002, and
      August 31, 2003, patients were identified at the time of hospitalization and were
      randomized to receive the intervention or usual care. The setting was a large
      integrated delivery system located in Colorado. Subjects (N = 750) included
      community-dwelling adults 65 years or older admitted to the study hospital with 1
      of 11 selected conditions. Intervention patients received (1) tools to promote
      cross-site communication, (2) encouragement to take a more active role in their
      care and to assert their preferences, and (3) continuity across settings and
      guidance from a "transition coach." Rates of rehospitalization were measured at
      30, 90, and 180 days. RESULTS: Intervention patients had lower rehospitalization
      rates at 30 days (8.3 vs 11.9, P = .048) and at 90 days (16.7 vs 22.5, P = .04)
      than control subjects. Intervention patients had lower rehospitalization rates
      for the same condition that precipitated the index hospitalization at 90 days
      (5.3 vs 9.8, P = .04) and at 180 days (8.6 vs 13.9, P = .046) than controls. The
      mean hospital costs were lower for intervention patients ($2058) vs controls
      ($2546) at 180 days (log-transformed P = .049). CONCLUSION: Coaching chronically
      ill older patients and their caregivers to ensure that their needs are met during
      care transitions may reduce the rates of subsequent rehospitalization.

PMID- 17000938
TI  - Cost-related medication nonadherence among elderly and disabled medicare
      beneficiaries: a national survey 1 year before the medicare drug benefit.
AB  - BACKGROUND: Prior to implementation of the Medicare drug benefit, we estimated
      the prevalence of cost-related medication nonadherence (CRN) among Medicare
      enrollees, including elderly and nonelderly disabled beneficiaries. METHODS: In
      the fall of 2004, detailed measures of CRN (skipping or reducing doses or not
      filling prescriptions because of cost) were added to the Medicare Current
      Beneficiary Survey. We examined the prevalence of CRN nationally and by Medicare
      eligibility subgroups (elderly vs nonelderly disabled beneficiaries), drug
      coverage status, socioeconomic status, self-rated health, and number of chronic
      medical conditions. RESULTS: In a national sample of 13 835 noninstitutionalized
      Medicare enrollees, 29% of the disabled and 13% of the elderly beneficiaries
      reported CRN; those in fair to poor health with multiple comorbidities and
      without coverage were most at risk. Among the disabled enrollees with 4 or more
      morbidities, 52% (95% confidence interval [CI], 43.3%-60.3%) without drug
      coverage skipped prescriptions or doses compared with 26% (95% CI, 17.7%-34.8%)
      with Medicaid drug coverage. Those with partial drug coverage through Medigap
      policies or Medicare health maintenance organizations reported intermediate rates
      of CRN. The adjusted odds ratio of CRN among disabled enrollees in poor (vs good)
      health was 3.9 (95% CI, 1.7-9.2), whereas for those with 4 or more (vs <4)
      comorbidities, the odds ratio of CRN was 2.7 (95% CI, 1.7-4.1). CONCLUSIONS: One
      year before Medicare Part D implementation, Medicare beneficiaries reported high
      rates of CRN. Rates are highest among nonelderly disabled beneficiaries, but
      among both elderly and disabled beneficiaries, CRN is exacerbated by poor health,
      multiple morbidities, and limited drug coverage. Given the high cost sharing
      under Part D, it is important to closely monitor CRN in high-risk subgroups.

PMID- 17000939
TI  - Effect of medication nonadherence on hospitalization and mortality among patients
      with diabetes mellitus.
AB  - BACKGROUND: Medication nonadherence may reduce the effectiveness of therapies. To
      our knowledge, the association between medication nonadherence and mortality
      remains unexplored outside the context of clinical trials. METHODS: A
      retrospective cohort study of 11 532 patients with diabetes mellitus in a managed
      care organization. Medication adherence was calculated as the proportion of days
      covered for filled prescriptions of oral hypoglycemics, antihypertensives, and
      statin medications. The primary outcomes of interest were all-cause
      hospitalization and all-cause mortality. Multivariable regression analyses were
      performed to assess the independent association between medication adherence and
      outcomes. RESULTS: Nonadherent patients (proportion of days covered, <80%;
      prevalence, 21.3%) were younger and had fewer comorbidities compared with
      adherent patients. During follow-up, nonadherent patients had higher glycosylated
      hemoglobin, systolic and diastolic blood pressure, and low-density lipoprotein
      cholesterol levels. In unadjusted analyses, nonadherent patients had higher all
      cause hospitalization (23.2% vs 19.2%, P<.001) and higher all-cause mortality
      (5.9% vs 4.0%, P<.001). In multivariable analyses, medication nonadherence
      remained significantly associated with increased risks for all-cause
      hospitalization (odds ratio, 1.58; 95% confidence interval, 1.38-1.81; P<.001)
      and for all-cause mortality (odds ratio, 1.81; 95% confidence interval, 1.46
      2.23; P<.001). The findings were consistent across patient subgroups and using
      different cutoffs for the proportion of days covered. CONCLUSIONS: Medication
      nonadherence is prevalent among patients with diabetes mellitus and is associated
      with adverse outcomes. Interventions are needed to increase medication adherence
      so that patients can realize the full benefit of prescribed therapies.

PMID- 17000940
TI  - Impact of medication therapy discontinuation on mortality after myocardial
      infarction.
AB  - BACKGROUND: Nonadherence to medications is common, but the determinants and
      consequences are poorly defined. The objectives of this study were to identify
      patient and myocardial infarction (MI) treatment factors associated with
      medication therapy discontinuation and to assess the impact of medication
      discontinuation 1 month after MI on 12-month mortality. METHODS: This was a
      multicenter prospective cohort of patients with MI enrolled in the Prospective
      Registry Evaluating Myocardial Infarction: Event and Recovery study. The outcomes
      were use of aspirin, beta-blockers, and statins at 1 month after MI
      hospitalization among patients discharged with all 3 medications as well as 12
      month mortality. RESULTS: Of 1521 patients discharged with all 3 medications, 184
      discontinued use of all 3 medications, 56 discontinued use of 2 medications, 272
      discontinued use of 1 medication, and 1009 continued taking all 3 medications at
      1 month. In multivariable analyses, patients not graduating from high school
      (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.20-2.60) were more likely
      to discontinue use of all medications. The effect of increasing age on medication
      therapy discontinuation was greater for females (OR, 1.77; 95% CI, 1.34-2.34)
      than males (OR, 1.23; 95% CI, 1.02-1.47). Patients who discontinued use of all
      medications at 1 month had lower 1-year survival (88.5% vs 97.7%; log-rank
      P<.001) compared with patients who continued to take 1 or more medication(s). In
      multivariable survival analysis, medication therapy discontinuation was
      independently associated with higher mortality (hazards ratio, 3.81; 95% CI, 1.88
      7.72). Results were consistent when evaluating discontinuation of use of aspirin,
      beta-blockers, and statins separately. CONCLUSIONS: Medication therapy
      discontinuation after MI is common and occurs early after discharge. Patients who
      discontinue taking evidence-based medications are at increased mortality risk.
      These findings suggest the need to improve the transition of care from the
      hospital to outpatient setting to ensure that patients continue to take
      medications that have mortality benefit.

PMID- 17000941
TI  - Improved therapeutic monitoring with several interventions: a randomized trial.
AB  - BACKGROUND: Medication errors are frequently related to failure to appropriately
      select medications or adjust for laboratory parameters. Differences between
      guideline recommendations and actual frequency of therapeutic laboratory
      monitoring are substantial. This study evaluated interventions to improve
      laboratory monitoring at initiation of medication therapy. METHODS: This cluster
      randomized trial compared 3 interventions to usual care for 10 medications in 15
      primary care clinics in a health maintenance organization with an electronic
      medical record system. Eligible patients, identified from electronic databases,
      had not received recommended laboratory monitoring within 5 days after new
      dispensing of a study medication. Interventions were an electronic medical record
      reminder to the prescribing health care professional, an automated voice message
      to the patient, and a pharmacy team outreach to the patient. Primary outcome was
      completion of all recommended baseline laboratory monitoring. RESULTS: A total of
      961 patients participated in the study. At 25 days, 95 (48.5%) of 196 patients in
      the electronic medical record reminder group, 177 (66.3%) of 267 in the automated
      voice message group, 214 (82.0%) of 261 in the pharmacy team outreach group, and
      53 (22.4%) of 237 in the usual care group had completed all recommended baseline
      laboratory monitoring (P<.001). After adjustments, the hazard ratios for
      completing laboratory monitoring compared with usual care were 2.5 (95%
      confidence interval, 1.8-3.5) for electronic medical record reminder, 4.1 (95%
      confidence interval, 3.0-5.6) for automated voice message, and 6.7 (95%
      confidence interval, 4.9-9.0) for pharmacy team outreach. CONCLUSIONS: All 3
      interventions were effective in increasing laboratory monitoring when initiating
      new medications in primary care. Further work is necessary to determine if these
      interventions improve patient outcomes.

PMID- 17000942
TI  - Physician communication when prescribing new medications.
AB  - BACKGROUND: Communication about taking a new medication is critical to proper use
      of drug therapy and to patient adherence. Despite ample evidence that medications
      are not taken as prescribed, few investigations have detailed the elements of
      communication about new medication therapy. This article describes and assesses
      the quality of physician communication with patients about newly prescribed
      medications. METHODS: This was an observational study that combined patient and
      physician surveys with transcribed audiotaped office visits from 185 outpatient
      encounters with 16 family physicians, 18 internists, and 11 cardiologists in 2
      Sacramento, Calif, health care systems between January and November 1999, in
      which 243 new medications were prescribed. We measured the quality of physician
      communication when prescribing new medications. RESULTS: Physicians stated the
      specific medication name for 74% of new prescriptions and explained the purpose
      of the medication for 87%. Adverse effects were addressed for 35% of medications
      and how long to take the medication for 34%. Physicians explicitly instructed 55%
      of patients about the number of tablets to take and explained the frequency or
      timing of dosing 58% of the time. Physicians fulfilled a mean of 3.1 of 5
      expected elements of communication when initiating new prescriptions. They
      counseled the most about psychiatric medications, fulfilling a mean of 3.7, 3.5,
      and 3.4, pulmonary, and cardiovascular elements, respectively. CONCLUSIONS: When
      initiating new medications, physicians often fail to communicate critical
      elements of medication use. This might contribute to misunderstandings about
      medication directions or necessity and, in turn, lead to patient failure to take
      medications as directed.

PMID- 17000943
TI  - Improved adherence and less toxicity with rifampin vs isoniazid for treatment of
      latent tuberculosis: a retrospective study.
AB  - BACKGROUND: Treatment of latent tuberculosis infection (LTBI) is an important
      aspect of tuberculosis control in the United States, but the effectiveness of
      this strategy is compromised by poor adherence to the recommended 9-month
      isoniazid regimen. In this study, we compared treatment completion and clinically
      recognized adverse drug reactions in patients prescribed 9 months of isoniazid
      therapy or 4 months of rifampin therapy for LTBI. METHODS: Retrospective chart
      review of patients who received LTBI treatment at a public health clinic.
      RESULTS: A total of 770 patients were prescribed 9 months of isoniazid therapy,
      and 1379 patients were prescribed 4 months of rifampin therapy. The percentages
      of patients who completed 80% or more of their prescribed treatment were 52.6%
      and 71.6% in the isoniazid and rifampin groups, respectively (P<.001). In
      multivariate logistic regression analysis, treatment regimen was independently
      associated with treatment completion (adjusted odds ratio for treatment
      completion, 2.88 for rifampin group vs isoniazid group; 95% confidence interval,
      2.27-3.66). Clinically recognized adverse reactions resulting in permanent
      treatment discontinuation occurred in 4.6% and 1.9% of patients in the isoniazid
      and rifampin groups, respectively (P<.001). Clinically recognized hepatotoxicity
      was more common in the isoniazid group (1.8%) than in the rifampin group (0.08%,
      P<.001). CONCLUSIONS: Compared with a 9-month isoniazid regimen, a 4-month
      rifampin regimen was associated with a higher percentage of patients completing
      treatment and a lower percentage of patients with clinically recognized adverse
      reactions. Additional studies are warranted to determine efficacy and
      effectiveness of rifampin therapy for LTBI.

PMID- 17000944
TI  - Diabetes mellitus and the risk of cancer: results from a large-scale population
      based cohort study in Japan.
AB  - BACKGROUND: An association between diabetes mellitus (DM) and cancer has long
      been speculated, but no conclusive evidence has been obtained. METHODS: We
      prospectively examined the association between a history of DM and subsequent
      risk of cancer in the Japan Public Health Center-Based Prospective Study. A total
      of 97 771 general Japanese persons (46 548 men and 51 223 women) aged 40 to 69
      years who responded to the baseline questionnaire, from January 1990 to December
      1994, were followed up for cancer incidence through December 31, 2003. At
      baseline, 6.7% of men and 3.1% of women had a history of DM. RESULTS: A total of
      6462 cases of newly diagnosed cancer were identified. In men, a 27% increase in
      the risk of total cancer incidence was observed in those with a history of DM (n
      = 3907 [366 with DM]; hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.14
      1.42). The HR was especially high for those with cancer of the liver (n = 312 [52
      with DM]; HR, 2.24; 95% CI, 1.64-3.04), pancreas (n = 118 [16 with DM]; HR, 1.85;
      95% CI, 1.07-3.20), and kidney (n = 99 [13 with DM]; HR, 1.92; 95% CI, 1.06
      3.46). We also observed a moderately increased risk of colon cancer (n = 491 [46
      with DM]; HR, 1.36; 95% CI, 1.00-1.85) and of stomach cancer with borderline
      significance (n = 977 [87 with DM]; HR, 1.23; 95% CI, 0.98-1.54). In women, a
      borderline significant increase in risk was observed for the incidence of total
      cancer (n = 2555 [104 with DM]; HR, 1.21; 95% CI, 0.99-1.47), while statistical
      significance was observed for the incidence of stomach cancer (n = 362 [20 with
      DM]; HR, 1.61; 95% CI, 1.02-2.54) and liver cancer (n = 120 [10 with DM]; HR,
      1.94; 95% CI, 1.00-3.73) and borderline significance was observed for the
      incidence of ovarian cancer (n = 74 [5 with DM]; HR, 2.42; 95% CI, 0.96-6.09).
      CONCLUSION: Patients with DM drawn from the general Japanese population may be at
      increased risk of total cancer and of cancer in specific sites.

PMID- 17000945
TI  - Adverse psychological and coronary risk profiles in young patients with coronary
      artery disease and benefits of formal cardiac rehabilitation.
AB  - BACKGROUND: Recent data indicate that young patients with coronary artery disease
      (CAD) have a poor long-term prognosis. Although the benefits of formal cardiac
      rehabilitation and exercise training programs are well established, most of these
      data come from middle-aged and older patients. METHODS: We assessed baseline
      behavioral data, quality of life, and risk profiles in 635 consecutive patients
      with CAD before and after cardiac rehabilitation and exercise training, and
      specifically assessed data in 104 young patients (mean +/- SD age, 48 +/- 6
      years; range, 22-54 years) compared with 260 elderly patients (mean +/- SD age,
      75 +/- 3 years; range, 70-85 years). RESULTS: Compared with older patients, young
      patients had higher body mass indexes (12.2%, P<.001), total cholesterol-high
      density lipoprotein ratio (14.6%, P<.01), and triglycerides level (27.2%, P<.01),
      and a lower high-density lipoprotein cholesterol level (-8.8%, P=.045). Young
      patients also had higher scores for anxiety and hostility (51.5% and 94.4%,
      respectively; P<.001 for both), a considerably higher prevalence of anxiety
      (27.9% vs 13.5%; P<.01) and hostility (12.5% vs 4.6%; P<.01) symptoms, and
      slightly more depression symptoms (23.1% vs 18.8%) compared with elderly
      patients. Following cardiac rehabilitation and exercise training, young patients
      had improvements in body mass index (-1.7%, P<.01), percentage body fat (-4.4%,
      P<.001), high-density lipoprotein cholesterol level (10.2%, P<.001), high
      sensitivity C-reactive protein level (-33.3%, P<.01), peak oxygen consumption
      (11.3%, P<.001), resting heart rate (-4.5%, P=.01), and resting systolic pressure
      (-2.3%, P=.049), and marked improvements in scores for depression (-58.5%),
      anxiety (-46.0%), hostility (-45.7%), somatization (-33.8%), and quality of life
      (15.8%) (P<.001 for all). Young patients also had greater than 50% to greater
      than 80% reductions in the prevalence of anxiety (P<.001), hostility (P<.01), and
      depression (P<.001). CONCLUSION: These data demonstrate the adverse psychological
      and CAD risk profiles that are present in young patients with CAD following major
      CAD events, and are consistent with substantial benefit of formal cardiac
      rehabilitation and exercise training programs in younger adults.

PMID- 17000946
TI  - Cardiovascular disease risk factors in chronic kidney disease: overall burden and
      rates of treatment and control.
AB  - BACKGROUND: Mild to moderate chronic kidney disease (CKD) is associated with
      increased risk for cardiovascular disease. The burden of cardiovascular disease
      risk factors in this setting is not well described. METHODS: We compared the age-
      and sex-adjusted prevalence of cardiovascular disease risk factors and their
      treatment and control among persons with and without CKD in 3258 Framingham
      offspring cohort members who attended the seventh examination cycle (1998-2001).
      Glomerular filtration rate (GFR) was estimated using the simplified Modification
      of Diet in Renal Disease Study equation. We defined CKD as a GFR of less than 59
      mL/min per 1.73 m(2) in women and less than 64 mL/min per 1.73 m(2) in men.
      RESULTS: Those with CKD were older, more likely to be obese (33.5% vs 29.3%;
      P=.02), and more likely to have low levels of high-density lipoprotein
      cholesterol (45.2% vs 29.4%; P<.001) and high triglyceride levels (39.9% vs
      29.8%; P<.001). Those with CKD had a higher prevalence of hypertension (71.2% vs
      42.7%; P<.001) and hypertension treatment (86.0% vs 72.5%; P<.001), but were less
      likely to achieve optimal blood pressure control (27.0% vs 45.5%; P<.001).
      Participants with CKD had a higher prevalence of elevated low-density lipoprotein
      cholesterol levels (60.5% vs 44.7%; P=.06) and lipid-lowering therapy (57.1% vs
      42.6%; P=.09), although this was not statistically significant. A greater
      proportion of individuals with CKD than those without had diabetes (23.5% vs
      11.9%; P=.02) and were receiving diabetes treatment (63.6% vs 46.9%; P=.05), but
      were less likely to achieve a hemoglobin A(1c) level of less than 7% (43.8% vs
      59.4%; P=.03). CONCLUSIONS: Chronic kidney disease is associated with a
      significant burden of cardiovascular disease risk factors in the community. The
      diagnosis of CKD should alert the practitioner to look for potentially modifiable
      cardiovascular risk factors.

PMID- 17000947
TI  - Long-term survival in elderly patients hospitalized for heart failure: 14-year
      follow-up from a prospective randomized trial.
AB  - BACKGROUND: The growing heart failure epidemic imposes a substantial burden on
      the US health care system. The ability to accurately assess prognosis would allow
      clinicians to triage patients to appropriate therapy and to plan the intensity of
      care following hospital discharge. METHODS: A cohort of 282 elderly (mean +/- SD
      age, 79.2 +/- 6.1 years) patients with heart failure were followed for up to 14
      years after enrollment in a prospective randomized multidisciplinary disease
      management trial conducted from 1990 through 1994. Kaplan-Meier survival curves
      were constructed to assess the probability of survival during the follow-up
      period. A Cox proportional hazards model was developed to identify independent
      predictors of long-term survival. C statistics were calculated to assess the
      utility of the model for predicting mortality at 6 months, 1 year, and 5 years.
      RESULTS: During the 14-year follow-up period, 269 patients (95%) died and the
      median survival was 894 days. Cox analysis identified 7 variables that were
      independent predictors of shorter survival time: older age (hazard ratio [HR],
      1.14 per 5 years; 95% confidence interval [CI], 1.03-1.26), serum sodium level
      less than 135 mEq/L (HR, 1.67; 95% CI, 1.19-2.32), coronary artery disease (HR
      1.51; 95% CI, 1.16-1.95), dementia (HR, 2.02; 95% CI, 1.13-3.61), peripheral
      vascular disease (HR, 1.74; 95% CI, 1.20-2.52), systolic blood pressure (HR, 0.95
      per 10 mm Hg; 95% CI, 0.92-0.98), and serum urea nitrogen level (HR, 1.20 per 10
      mg/dL [3.57 mmol/L]; 95% CI, 1.12-1.29). C statistics for the model were 0.84,
      0.79, and 0.75 at 6 months, 1 year, and 5 years, respectively. A risk score for
      mortality was developed using the 7 independent predictor variables. One-year
      mortality rates among patients with 0 to 1 (n = 89), 2 to 3 (n = 153), and 4 or
      more (n = 37) risk factors were 9.0%, 22.2%, and 73.0%, respectively (P<.001).
      CONCLUSIONS: Among elderly patients hospitalized with heart failure, median
      survival is about 2.5 years. However, there is considerable heterogeneity in
      survival, with 25% of patients dying within 1 year and 25% surviving for more
      than 5 years. A simple 7-item risk score, based on data readily available at the
      time of admission, provides a reliable estimate of prognosis.

PMID- 17000948
TI  - A meta-analysis of controlled clinical studies with diacerein in the treatment of
      osteoarthritis.
AB  - BACKGROUND: This systematic meta-analysis on randomized controlled trials with
      diacerein was performed to provide an evidence-based assessment of its
      symptomatic efficacy in the treatment of osteoarthritis. METHODS: Electronic
      databases were searched for randomized controlled trials with diacerein. A manual
      review of the literature, abstracts, and posters was also conducted. Unpublished
      final reports were obtained from the manufacturer. Only studies performed in knee
      and/or hip osteoarthritis were chosen for review. Study inclusion, quality
      scoring, and data extraction were performed by 2 reviewers independently.
      Objectives for analysis comprised pain, function, escape medication use, global
      efficacy, and safety ratings by patients and investigators. Specific study
      periods, such as the active treatment period and the treatment-free follow-up
      period (when present), were analyzed. Statistical analyses were based on the
      intention-to-treat principle as far as possible, and acknowledged tests were used
      for data analysis. RESULTS: A total of 23 studies were identified, 19 of which
      were included. Diacerein was significantly superior to placebo during the active
      treatment phase (Glass score, 1.50 [95% confidence interval, 0.80-2.20]). Both
      diacerein and nonsteroidal anti-inflammatory drugs (NSAIDs) were similarly
      efficacious during the treatment period; however, diacerein, but not NSAIDs,
      showed a carryover effect, persisting up to 3 months after treatment, with a
      significant analgesic-sparing effect during the follow-up period (Glass score,
      2.06 [95% confidence interval, 0.66-3.46]). Tolerability assessment revealed no
      differences between diacerein and NSAIDs, although the latter showed more severe
      events. CONCLUSION: This systematic meta-analysis provides evidence for the
      symptomatic efficacy of diacerein in the treatment of knee and hip
      osteoarthritis, with reasonable tolerability.

PMID- 17000949
TI  - Ethnic differences among patients with cutaneous melanoma.
AB  - BACKGROUND: Melanoma incidence continues to increase in whites, but little is
      known about melanoma in minority populations. Surveillance, Epidemiology, and End
      Results (SEER) data were used to examine the incidence, manifestations, and
      survival in patients with melanoma with respect to race/ethnicity. METHODS: A
      SEER search (1992-2002) for primary invasive cutaneous melanoma cases identified
      48 143 whites, 932 Hispanics, 394 Asian/Pacific islanders, 251 African Americans,
      and 52 American Indians. Multivariate analyses were performed to evaluate the
      relationship between race/ethnicity and clinicopathologic factors; associations
      between race/ethnicity and survival were examined using the Cox proportional
      hazards model. RESULTS: Based on our cohort of patients, the average annual age
      adjusted melanoma incidence per 100 000 persons was 18.4 for whites compared with
      2.3, 0.8, 1.6, and 1.0 for Hispanics, African Americans, American Indians, and
      Asians, respectively. Lower extremity and acral lentiginous melanomas were more
      common among minorities. Overall 5-year survival was 72.2% to 81.1% for
      minorities compared with 89.6% for whites. A 1.96- to 3.01-fold greater risk of
      disease-specific mortality persisted in minorities compared with whites after
      adjusting for age, sex, and region. In addition, Hispanics (odds ratio [OR],
      3.6), African Americans (OR, 4.2), American Indians (OR, 3.4), and Asians (OR,
      2.4) were more likely to present with stage IV melanoma than were whites. African
      Americans had a 1.48-fold higher rate of risk-adjusted, stage-specific mortality
      compared with whites. CONCLUSIONS: Melanoma is a public health concern for all
      ethnic populations. Differences in disease stage at presentation contributes to
      disparities in survival. Understanding melanoma in minority populations may lead
      to early detection and ultimately save lives.

PMID- 17000950
TI  - Menthol cigarettes, smoking cessation, atherosclerosis, and pulmonary function:
      the Coronary Artery Risk Development in Young Adults (CARDIA) Study.
AB  - BACKGROUND: African American smokers are more likely to experience tobacco
      related morbidity and mortality than European American smokers, and higher rates
      of menthol cigarette smoking may contribute to these disparities. METHODS: We
      prospectively measured cumulative exposure to menthol and nonmenthol cigarettes
      and smoking cessation behavior (1985-2000), coronary calcification (2000), and 10
      year change in pulmonary function (1985-1995) in African American and European
      American smokers recruited in 1985 for the Coronary Artery Risk Development in
      Young Adults Study. RESULTS: We identified 1535 smokers in 1985 (972 menthol and
      563 nonmenthol); 89% of African Americans preferred menthol vs 29% of European
      Americans (P<.001). After adjustment for ethnicity, demographics, and social
      factors, we found nonsignificant trends in menthol smokers toward lower cessation
      (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.49-1.02; P = .06) and
      recent quit attempt (OR, 0.77; 95% CI, 0.56-1.06; P = .11) rates and a
      significant increase in the risk of relapse (OR, 1.89; 95% CI, 1.17-3.05; P =
      .009). Per pack-year of exposure, however, we found no differences from menthol
      in tobacco-related coronary calcification (adjusted OR, 1.27; 95% CI, 1.01-1.60
      for menthol cigarettes and 1.33; 95% CI, 1.06-1.68 for nonmenthol cigarettes per
      10-pack-year increase; P = .75 for comparison) or 10-year pulmonary function
      decline (adjusted excess decline in forced expiratory volume in 1 second, 84 mL;
      95% CI, 32-137 for menthol cigarettes and 80 mL; 95% CI, 30-129 for nonmenthol
      cigarettes, per 10-pack-year increase; P = .88 for comparison). CONCLUSION:
      Menthol and nonmenthol cigarettes seem to be equally harmful per cigarette smoked
      in terms of atherosclerosis and pulmonary function decline, but menthol
      cigarettes may be harder to quit smoking.

PMID- 17000951
TI  - Erythropoietin resistance during androgen deficiency.

PMID- 17000952
TI  - Neurology patient page. Facing reality: the cost of Alzheimer dementia--who will
      pay?

PMID- 17000953
TI  - Benign and malignant pathology in neurofibromatosis type 1.

PMID- 17000954
TI  - How much can we learn from long-term extension trials in multiple sclerosis?

PMID- 17000955
TI  - Spontaneous cervical artery dissection: is there a gender innuendo?

PMID- 17000956
TI  - Is "compassionate use" compassionate?: rFVIIa for intracerebral hemorrhage.

PMID- 17000957
TI  - Survey of training programs' means for promoting neurology and attracting
      trainees.
AB  - OBJECTIVE: To determine neurology training opportunities available to medical
      students and to define factors that influence program choice. METHODS: All
      neurology residency program directors and a random sample of residents were
      surveyed. Resident questions related to application, interview, and training
      experience. Directors' questions focused on ways their department generated
      interest in clinical neurosciences. RESULTS: Medical schools introduce students
      to clinical neurology primarily through required clerkships. Contact time
      averages less than 4 weeks and emphasizes inpatient encounters. Preceptorships
      with neurology faculty do not exist at almost 40% of schools and only 14% have
      neuroscience tracks. Nearly all residency applicants matched their first or
      second choice. The majority declined at least one interview and 39% failed to
      rank at least one site they visited. When choosing where to apply, the programs'
      reputation and geographic considerations were paramount. When making a rank list,
      interactions with faculty and residents at interview were most important.
      Residents generally reported satisfaction with their programs and attribute
      morale to supportive relationships with faculty and residents. CONCLUSIONS:
      Neurology programs may be able to enhance students' impression of neurology
      through changes in their clinical experience and development of venues for more
      meaningful relationships with faculty. Attention to the residents' personal needs
      may increase the likelihood of matching the best available candidates and
      ensuring their satisfaction.

PMID- 17000958
TI  - Severe tongue protrusion dystonia: clinical syndromes and possible treatment.
AB  - We describe intermittent or sustained severe involuntary tongue protrusion in
      patients with a dystonic syndrome. Speech, swallowing, and breathing difficulties
      can be severe enough to be life threatening. Causes include neuroacanthocytosis,
      pantothenate kinase-associated neurodegeneration, Lesch-Nyhan syndrome, and
      postanoxic and tardive dystonia. The pathophysiology of intermittent severe
      tongue protrusion remains unknown. Tongue protrusion dystonia is often
      unresponsive to oral drugs but may benefit from botulinum toxin injections into
      the genioglossus muscle. Bilateral deep brain pallidal stimulation was beneficial
      in two cases.

PMID- 17000959
TI  - Long-term subcutaneous interferon beta-1a therapy in patients with relapsing
      remitting MS.
AB  - OBJECTIVE: To conduct systematic long-term follow-up (LTFU) of patients in the
      Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in
      Multiple Sclerosis (PRISMS) study to provide up to 8 years of safety, clinical
      and MRI outcomes on subcutaneous (s.c.) interferon (IFN) beta-1a in relapsing
      remitting multiple sclerosis (RRMS). METHODS: The original cohort of 560 patients
      was randomized to IFNbeta-1a, 44 or 22 microg three times weekly (TIW) or to
      placebo; after 2 years, patients on placebo were rerandomized to active treatment
      and the blinded study continued for a further 4 years. The LTFU visit was
      scheduled 7 to 8 years after baseline. RESULTS: LTFU was attended by 68.2% of the
      original PRISMS study cohort (382/560 patients). 72.0% (275/382) were still
      receiving IFNbeta-1a s.c. TIW. Patients originally randomized to IFNbeta-1a 44
      microg s.c. TIW showed lower Expanded Disability Status Scale progression,
      relapse rate and T2 burden of disease up to 8 years compared with those in the
      late treatment group. Brain parenchymal volume did not show differences by
      treatment group. Overall, 19.7% of patients progressed to secondary progressive
      MS between baseline and LTFU (75/381). No new safety concerns were identified and
      treatment was generally well tolerated. CONCLUSIONS: Despite the limitations
      inherent in any long-term study (for example, potential differences between
      returning and nonreturning patients), these results indicate that patients with
      relapsing-remitting multiple sclerosis can experience sustained benefit over many
      years from early interferon beta-1a subcutaneous therapy three times weekly
      compared with patients whose treatment is delayed. This effect was more apparent
      in the patients receiving the higher dose.

PMID- 17000960
TI  - Is late-onset multiple sclerosis associated with a worse outcome?
AB  - OBJECTIVE: To describe the characteristics of late-onset multiple sclerosis (MS)
      (LOMS, 50+ years) vs adult-onset MS (AOMS, 16 to <50 years) and examine prognosis
      and associated risk factors. METHODS: Patients with definite MS, onset prior to
      July 1988, registered with a BCMS clinic before July 1998, with at least one
      Expanded Disability Status Scale (EDSS) score, were selected from the
      longitudinal population-based British Columbian (BC) MS database. Clinical and
      demographic characteristics were compared between LO and AOMS. Progression was
      measured as time to reach sustained EDSS 6 and potential risk factors examined
      were sex, disease course (primary progressive [PP] vs relapsing [R]), and onset
      symptoms. RESULTS: Of those eligible (n = 2,837), LOMS comprised 132 (4.7%), with
      PPMS predominating (54.5% vs 10.6% in AOMS, p < 0.0005). Motor onset symptoms
      were more prevalent in LOMS and sensory and optic neuropathy more prevalent in
      AOMS (p < 0.0005). AOMS averaged 27.7 years (95% CI: 26.3 to 29.1) to EDSS 6 from
      onset vs 16.9 years (95% CI: 9.0 to 24.8) in LOMS, p < 0.0005. However, AOMS was
      associated with a younger age at EDSS 6 (58.4 years [95% CI: 57.1 to 59.6] vs
      71.2 years [95% CI: 65.2 to 77.3] in LOMS, p < 0.0005). There were no differences
      in progression between AO or LO for those with PPMS (p = 0.373) or R-MS (p =
      0.438), although considerable variation was observed. CONCLUSIONS: Late-onset
      multiple sclerosis (LOMS) is not necessarily associated with a worse outcome:
      first, progression in the primary progressive or relapsing patients differed
      little between late-onset vs adult-onset; secondly, those with LOMS were older
      when reaching Expanded Disability Status Scale 6. The disease course has a far
      greater implication for disease prognosis than the presence of LOMS.

PMID- 17000961
TI  - Neocortical neuronal, synaptic, and glial loss in multiple sclerosis.
AB  - BACKGROUND: Recent pathologic investigations have shown that neocortical lesions
      are frequent in multiple sclerosis (MS). Structural MRI has shown that
      neocortical atrophy occurs early and can be substantial, but the specific
      substrate for this atrophy has not been defined quantitatively. OBJECTIVE: To
      investigate cortical thickness as well as neuronal, glial, and synaptic densities
      in MS. METHODS: We studied brain samples from 22 patients with MS and 17 control
      subjects. Neocortical lesions and cortical thickness were assessed on sections
      stained for myelin basic protein. Neuronal, glial, and synaptic densities were
      measured in type I leukocortical lesions, nonlesional neocortex, and non-MS
      control cortex. Immunoautoradiography was used to quantify synaptic densities.
      RESULTS: Neocortical lesions were common in patients with MS. Subpial type III
      (44%) and leukocortical type I (38%) lesions were more abundant than
      intracortical type II (18%) lesions. An overall relative neocortical thinning of
      10% (p = 0.016) was estimated for the patients. Within the type I lesions, we
      found evidence for substantial cell (glial, 36%, p = 0.001; neuronal, 10%, p =
      0.032) and synaptic (47% decrease in synaptophysin, p = 0.001) loss. Nonlesional
      neocortex did not show significant relative changes in neuronal, glial, or
      synaptic density. CONCLUSIONS: Neocortical neuronal and glial degeneration is
      significant in multiple sclerosis. Synaptic loss was particularly striking in the
      neocortical lesions, which should make a major independent contribution to the
      expression of pathology. New therapies should be directed toward limiting this
      damage.

PMID- 17000962
TI  - Baseline MRI predicts future attacks and disability in clinically isolated
      syndromes.
AB  - OBJECTIVE: To determine the relation between baseline MRI and both conversion to
      multiple sclerosis (MS) and development of disability in a cohort of patients
      with clinically isolated syndromes (CIS). METHODS: From 1995 to 1998, 175
      consecutive patients with CIS underwent brain MRI within 3 months of their first
      attack and again 12 months and 5 years later. We studied the number and location
      of lesions at baseline and development of new T2 lesions. We also analyzed
      conversion to MS and development of disability (Expanded Disability Status Scale
      [EDSS] > or = 3.0). RESULTS: We included 156 patients with CIS followed for a
      median of 7 years. Compared to the reference group with 0 Barkhof criteria at
      baseline MRI, patients with one or two Barkhof criteria showed an adjusted hazard
      ratio (HR) of 6.1 (2.2 to 16.6) and patients with three to four Barkhof criteria
      of 17.0 (6.7 to 43) for conversion to MS and differentiated patients with low,
      medium, and high conversion risk. EDSS at year 5 correlated with baseline number
      of Barkhof criteria (r = 0.46, p < 0.0001). When categorizing by number of
      baseline lesions, similar results were seen. Patients with a baseline MRI with
      three to four Barkhof criteria had an adjusted HR of 3.9 (1.1 to 13.6) for
      reaching EDSS > or = 3.0. Only 10% of the latter had disability at year 5, but
      40% reached this at 8 years. CONCLUSIONS: Baseline MRI determines the risk for
      converting to clinically definite multiple sclerosis and correlates with
      disability at 5 years. The proportion of patients developing disability is low
      during the first 5 years but rapidly increases shortly after.

PMID- 17000963
TI  - Evidence of publication bias in reporting acute stroke clinical trials.
AB  - OBJECTIVE: To ascertain the extent of publication bias in the reporting of acute
      stroke clinical trials. METHODS: We identified controlled acute ischemic stroke
      clinical trials reported in English over a 45-year period from 1955 to 1999
      through systematic search of MEDLINE, the Cochrane Controlled Stroke Trials
      Register, and additional databases. We analyzed trial methodology, quality,
      outcome, study sponsorship, and timing of publication to identify various forms
      of publication bias, including nonpublication bias, abbreviated publication bias,
      and time-lag bias. RESULTS: One hundred seventy-eight acute ischemic stroke
      trials, enrolling 73,949 subjects, evaluated 75 agents or nonpharmacologic
      interventions. A greater proportion of harmful outcomes in unpublished studies (n
      = 4) compared with published trials (0.75 vs 0.06, p < 0.0001) and underreporting
      of smaller, nonbeneficial studies in acute stroke suggest nonpublication bias.
      Although a definite time-lag bias was not evident, nonbeneficial studies were
      slower to proceed from enrollment completion to publication (2.3 vs 2.0 years, p
      = 0.207), with an even longer delay for nonbeneficial corporate pharmaceutical
      sponsored trials (2.8 vs 2.1 years, p = 0.086), despite superior trial report
      quality scores for corporate-sponsored studies when compared with
      nonprofit/governmental studies (mean 69.2 +/- 95% CI 3.9 vs 53.4 +/- 95% CI 9.2,
      p < 0.005). CONCLUSION: Publication bias is evident in the acute stroke research
      literature, supporting the need for prospective trial registration.

PMID- 17000964
TI  - Early MRI and outcomes of untreated patients with mild or improving ischemic
      stroke.
AB  - OBJECTIVE: To determine the frequency of early neurologic deterioration with
      infarct expansion (ENDIE) and poor outcomes among ischemic stroke patients not
      treated with reperfusion therapies because of rapidly improving or mild symptoms
      (RIMS) and to study the predictive value of hyperacute MRI in these patients.
      METHODS: We identified consecutive patients with symptoms of acute stroke
      undergoing multimodal MRI within 6 hours of onset without evidence of hemorrhage
      on imaging. Medical records were reviewed for evidence of early neurologic
      deterioration within 48 hours. All deteriorating patients had repeat MRI to
      ascertain causes of worsening. Poor outcome was defined as a discharge modified
      Rankin Scale (mRS) score of > or = 3. RESULTS: We identified 74 patients with
      stroke symptoms < or = 6 hours from onset. Forty had RIMS, and 39 did not receive
      reperfusion therapies because of RIMS. Among these 39, 4 experienced ENDIE, and 8
      were discharged with mRS score of > or = 3. Eight of the 39 patients had large
      vessel occlusions on MR angiography. Three of 8 patients with large-vessel
      occlusion as against only one of 31 patients without occlusion had ENDIE (odds
      ratio [OR] 18, 95% CI 1.6 to 209, p = 0.02). Four of 8 patients with large-vessel
      occlusion as against 4 of 31 patients without occlusion had a discharge mRS score
      of > or = 3 (OR 7, 95% CI 1.2 to 38, p = 0.04). CONCLUSIONS: About 10% of
      patients eligible for acute reperfusion therapy excluded on the basis of mild or
      rapidly improving symptoms show early neurologic deterioration with infarct
      expansion within 48 hours, and about 20% show poor outcome at discharge.
      Persisting large-vessel occlusion substantially increases the risk of early
      worsening and poor functional outcome.

PMID- 17000965
TI  - Cross-sectional association between homocysteine and motor function in the
      elderly.
AB  - OBJECTIVE: To determine if there is a cross-sectional association between
      homocysteine (tHcy) level and measures of gait and balance in elderly subjects.
      METHODS: We studied 3,609 noninstitutionalized subjects aged 65 to 85 years from
      the Dijon (France) center of the Three-City Study. tHcy concentration was
      measured from fasting blood samples. Motor function was assessed by measuring
      walking speed and by using a modified version of the Tinetti scale. RESULTS:
      After adjustment for confounders, mean maximum walking speed (MWS) decreased with
      increasing tHcy levels (p = 0.001). The odds ratio (OR) (95% CI) for having a MWS
      below the 40th percentile was 1.9 (1.4 to 2.5) in subjects with tHcy levels in
      the upper quintile compared with those in the lowest quintile. Compared with
      subjects in the lowest tHcy quintile, the OR for having a modified Tinetti score
      below 16 ranged from 1.0 (0.8 to 1.4) in the second quintile to 1.9 (1.3 to 2.6)
      in the upper quintile (p < 0.0001). CONCLUSIONS: Elevated homocysteine
      concentrations are associated with worse motor performances in the elderly. These
      findings support the hypothesis of a vascular contribution to motor function.

PMID- 17000966
TI  - Cerebral vasospasm in idiopathic thunderclap headache.

PMID- 17000967
TI  - High-frequency chest wall oscillation in ALS: an exploratory randomized,
      controlled trial.
AB  - OBJECTIVES: To evaluate changes in respiratory function in patients with ALS
      after using high-frequency chest wall oscillation (HFCWO). METHODS: This was a 12
      week randomized, controlled trial of HFCWO in patients with probable or definite
      ALS, an Amyotrophic Lateral Sclerosis Functional Rating Scale respiratory
      subscale score < or = 11 and > or = 5, and forced vital capacity (FVC) > or = 40%
      predicted. RESULTS: We enrolled 46 patients (58.0 +/- 9.8 years; 21 men, 25
      women); 22 used HFCWO and 24 were untreated. Thirty-five completed the trial: 19
      used HFCWO and 16 untreated. HFCWO users had less breathlessness (p = 0.021) and
      coughed more at night (p = 0.048) at 12 weeks compared to baseline. At 12 weeks,
      HFCWO users reported a decline in breathlessness (p = 0.048); nonusers reported
      more noise when breathing (p = 0.027). There were no significant differences in
      FVC change, peak expiratory flow, capnography, oxygen saturation, fatigue, or
      transitional dyspnea index. When patients with FVC between 40 and 70% predicted
      were analyzed, FVC showed a significant mean decrease in untreated patients but
      not in HFCWO patients; HFCWO patients had significantly less increased fatigue
      and breathlessness. Satisfaction with HFCWO was 79%. CONCLUSION: High-frequency
      chest wall oscillation was well tolerated, considered helpful by a majority of
      patients, and decreased symptoms of breathlessness. In patients with impaired
      breathing, high-frequency chest wall oscillation decreased fatigue and showed a
      trend toward slowing the decline of forced vital capacity.

PMID- 17000968
TI  - Sudden death after air travel in a patient with colloid cyst.

PMID- 17000969
TI  - Age, gender, and education norms on the CERAD neuropsychological battery in the
      oldest old.
AB  - OBJECTIVE: To evaluate the performance of nondemented subjects 85 years and older
      on the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
      neuropsychological battery, and to assess its relationship with sociodemographic
      variables. METHODS: We studied 196 subjects enrolled in an Alzheimer's Disease
      Research Center study who had a complete CERAD neuropsychological assessment. We
      used multiple regression analysis to predict performance on the
      neuropsychological tests from age, education, and sex. Eight representative
      hypothetical individuals were created (for example, an 87-year-old man, with high
      education). For each test, estimates of performance at the 10th, 25th, 50th, and
      75th percentiles were reported for the eight representative hypothetical
      individuals. RESULTS: Mean age was 89.2 years (SD = 3.2), mean years of education
      was 14.9 (SD = 3.2), and 66% of the sample were women. For 11 of the 14
      neuropsychological tests, there was a significant multiple regression model using
      education, age, and sex as predictors. Neither the models nor the predictors used
      individually were significant for Delayed Recall, Savings, or correct
      Recognition. Among the significant results, seven had education as the strongest
      predictor. Lower age and higher education were associated with better
      performance. Women performed better than men in three of four tests with
      significant results for sex. CONCLUSIONS: In a sample of oldest old whose primary
      language is English, neuropsychological testing is influenced mainly by education
      and age. Cutoff scores based on younger populations and applied to the oldest old
      might lead to increased false-positive misclassifications.

PMID- 17000970
TI  - Brain mechanisms of successful compensation during learning in Alzheimer disease.
AB  - OBJECTIVE: To determine whether patients with Alzheimer disease (AD) compensate
      for neuropathologic changes when performing a mnemonic task by recruiting 1) the
      same brain regions as age-matched, healthy controls, but to a greater extent; 2)
      additional brain regions not activated by controls; or 3) both. METHODS: Twelve
      patients with mild probable AD and 12 healthy age- and education-matched controls
      participated in an fMRI study of successful encoding and retrieval of
      visuospatial paired associates. To ensure successful performance in both groups,
      participants were given multiple attempts to learn associations between two and
      three object locations. RESULTS: The pattern of brain activity in patients with
      AD performing an easy version of the task was indistinguishable from that of
      controls performing a harder version of the task. Increased activation in left
      medial and right lateral prefrontal cortices was found in patients with AD
      compared to controls during encoding of two object locations, but not when this
      level of encoding in patients was compared with encoding of three object
      locations in controls. CONCLUSIONS: There was no evidence of neural plasticity in
      the form of recruitment of novel brain regions in patients with Alzheimer
      disease. Data supported greater recruitment of the same brain regions as age
      matched controls as a means of compensating for neuropathology and associated
      cognitive impairment in Alzheimer disease.

PMID- 17000971
TI  - Sleep deprivation increases cortical excitability in epilepsy: syndrome-specific
      effects.
AB  - OBJECTIVE: To use transcranial magnetic stimulation (TMS) to investigate the
      hypothesis that sleep deprivation increases cortical excitability in people with
      epilepsy. METHODS: We performed paired pulse TMS stimulation, using a number of
      interstimulus intervals (ISIs) on each hemisphere of 30 patients with untreated
      newly diagnosed epilepsy (15 idiopathic generalized epilepsy [IGE] and 15 focal
      epilepsy) and on the dominant hemisphere of 13 healthy control subjects, before
      and after sleep deprivation. RESULTS: Both hemispheres in patients with IGE and
      the hemisphere ipsilateral to the EEG seizure focus in those with focal epilepsy
      showed an increase in cortical excitability following sleep deprivation at a
      number of ISIs. This change in excitability was most prominent in the patients
      with IGE. Although there were minor changes after sleep deprivation in control
      subjects and the contralateral hemisphere in the focal epilepsy group seen at the
      250-millisecond ISI, it was less than in the other groups. CONCLUSIONS: Sleep
      deprivation increases cortical excitability in epilepsy; the pattern of change is
      syndrome dependent.

PMID- 17000972
TI  - Volumetric MRI differences in treatment-naive vs chronically treated children
      with ADHD.
AB  - OBJECTIVE: To determine if there are differences in the volume of the caudate and
      anterior cingulate cortex (ACC) between children with attention deficit
      hyperactivity disorder (ADHD) and controls, and if such differences are related
      to the subjects' history of stimulant treatment. METHODS: We performed a case
      control study in an academic medical center. Twenty-one healthy controls, 16
      children with ADHD, combined type with a history of stimulant treatment, and 14
      children with ADHD, combined type treatment naive, underwent structural MRI. All
      children with ADHD were medication-free at the time of the MRI. Regional
      hemispheric volumes (in cm3) of caudate and anterior cingulate cortex were
      determined. RESULTS: There were significant differences bilaterally on caudate
      volume for both ADHD groups vs controls, with no difference between the ADHD
      groups on either side. In contrast, the right ACC was significantly smaller for
      the ADHD-treatment naive (ADHD/TN) group compared to the ADHD-treated (ADHD/Rx)
      and control group. The volume of left ACC approached significance contrast
      between ADHD/RX and ADHD/TN. There were no differences found between the ADHD/Rx
      and controls on the ACC volumes bilaterally. CONCLUSIONS: The results from this
      study indicate a relationship of previous treatment history with caudate and
      anterior cingulate volumetric changes in children with attention deficit
      hyperactivity disorder-combined type.

PMID- 17000973
TI  - Migrainous vertigo: prevalence and impact on quality of life.
AB  - OBJECTIVE: To investigate the epidemiology of migrainous vertigo (MV) in the
      general population by assessing prevalence, clinical features, comorbid
      conditions, quality of life, and health care utilization. METHODS: We screened a
      representative sample of the adult population in Germany (n = 4,869) for moderate
      or severe dizziness/vertigo and followed up with validated neurotologic telephone
      interviews (n = 1,003). Diagnostic criteria for MV were as follows: 1) recurrent
      vestibular vertigo; 2) migraine according to the International Headache Society;
      3) migrainous symptoms during at least two vertiginous attacks (migrainous
      headache, photophobia, phonophobia, or aura symptoms); and 4) vertigo not
      attributed to another disorder. In a concurrent validation study (n = 61) the
      interviews had a sensitivity of 84% and a specificity of 94% for vestibular
      vertigo and 81% and 100% for migraine. RESULTS: The lifetime prevalence of MV was
      0.98% (95% CI 0.70 to 1.37), the 12-month prevalence 0.89% (95% CI 0.62 to 1.27).
      Spontaneous rotational vertigo was reported by 67% of participants with MV while
      24% had positional vertigo. Twenty-four percent always experienced headaches with
      their vertigo. Logistic regression analysis comparing participants with MV with
      dizziness-free migraineurs showed an independent association with coronary heart
      disease but not with sex, age, migrainous aura, education, stroke, hypertension,
      hyperlipidemia, body mass index, or depression. Age-adjusted health-related
      quality of life scores (SF-8 Health Survey) were consistently lower in
      participants with MV compared to dizziness-free controls. Two thirds of
      participants with MV had consulted a doctor but only 20% of these were diagnosed
      with MV. CONCLUSIONS: Migrainous vertigo is relatively common but underdiagnosed
      in the general population and has considerable personal and healthcare impact.

PMID- 17000974
TI  - First seizure presentation: do multiple seizures within 24 hours predict
      recurrence?
AB  - We compared clinical features and prognosis of 72 adults with a first-ever
      seizure presentation comprising multiple discrete seizures within 24 hours to 425
      patients presenting with a single seizure. Those presenting with multiple
      seizures were no more likely to have seizure recurrence, irrespective of etiology
      or treatment. Hence, a presentation with multiple seizures within 24 hours should
      be regarded as a single event, in keeping with the International League Against
      Epilepsy recommendations.

PMID- 17000975
TI  - Gender differences in spontaneous cervical artery dissection.
AB  - We analyzed sex differences in 696 patients with spontaneous cervical artery
      dissection. There were more men (n = 399; p < 0.0001), and men showed a higher
      frequency of hypertension (31% vs 15%; p < 0.0001). Women were younger (42.5 +/-
      9.9 vs 47.5 +/- 9.3 years; p < 0.0001), had more often multiple dissections (18
      vs 10%; p = 0.001), migraine (47 vs 20%; p < 0.0001), and tinnitus (16 vs 8%; p =
      0.001). Outcome and mortality were similar in both sexes.

PMID- 17000976
TI  - Myocardial injury in patients with intracerebral hemorrhage treated with
      recombinant factor VIIa.
AB  - We report myocardial injury in 20 recombinant factor VIIa (rFVIIa) treated and
      110 nontreated patients with intracerebral hemorrhage. Patients were treated or
      received standard medical management. All received EKG and cardiac enzyme
      testing. Elevated troponin occurred in 20% treated vs 3% nontreated (p = 0.02).
      Myocardial infarction occurred in 10% vs 1% (p = 0.01). We found a significant
      increase in myocardial injury in rFVIIa treated patients.

PMID- 17000978
TI  - No indication of brain reorganization after unilateral ischemic lesions of the
      auditory cortex.
AB  - We used magnetoencephalography to study contralesional auditory reorganization in
      three men with chronic unilateral ischemic lesions of the auditory cortex.
      Although no response was found over the lesioned hemisphere, processing in the
      unaffected hemisphere was indistinguishable vs healthy controls. In contrast to
      sensorimotor and language systems, the auditory system seems to lack
      contralateral reorganization, presumably because patients are typically not aware
      of hearing deficits and thus do not perform training.

PMID- 17000977
TI  - Changes of brachial flow-mediated vasodilation in different ischemic stroke
      subtypes.
AB  - The relationship between endothelial dysfunction and stroke subtypes is unclear.
      We prospectively measured brachial flow-mediated vasodilation (FMD) in 143
      patients with acute ischemic stroke and 40 controls. The overall stroke patients
      had impaired FMD, but only lacunar infarction had significantly impaired FMD vs
      the controls. Impaired FMD was an independent predictor for lacunar infarction.
      Ischemic stroke is associated with endothelial dysfunction, which is more
      conspicuous in lacunar infarction.

PMID- 17000979
TI  - Multiple sclerosis with and without CSF bands: clinically indistinguishable but
      immunogenetically distinct.
AB  - We sought to determine whether Swedish patients with multiple sclerosis (MS) with
      and without oligoclonal bands (OCBs) in the CSF constitute distinct
      subpopulations, clinically and immunogenetically. Our findings indicate that OCB
      negative MS shares the same clinical features as OCB-positive MS regarding female
      predominance, age at onset, proportion of primary progressive cases, rate of MRI
      positivity, and disease severity. Our HLA-DRB1 genotyping results suggest,
      however, that OCB-positive and OCB-negative MS are immunogenetically distinct.

PMID- 17000980
TI  - Leukoencephalopathy induced by levamisole alone for the treatment of recurrent
      aphthous ulcers.
AB  - We report imaging and clinical findings of leukoencephalopathy occurring after
      levamisole. The lesions were hypoattenuating on CT and appeared as multifocal
      oval or elliptical foci in the white matter or along the subependymal veins on
      MRI. Most lesions resolve after prompt withdrawal of levamisole. Detailed history
      taking is important for diagnosing levamisole-induced leukoencephalopathy because
      multiple sclerosis and acute disseminated encephalomyelitis cannot be
      differentiated by neuroimaging findings alone.

PMID- 17000981
TI  - Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies.
AB  - We report five of 38 patients with stiff person syndrome (SPS), who also had
      cerebellar disease, gait ataxia, dysarthria, and oculomotor dysfunction (SPS
      Cer). Cerebellar manifestations either preceded SPS or occurred concurrently.
      Brain MRI was normal. The intrathecal production of glutamic acid decarboxylase
      antibodies was elevated. Gamma-aminobutyric acid-enhancing drugs and
      immunotherapies improved only the stiffness. SPS-Cer is a distinct subset of SPS
      causing a more severe and complex clinical phenotype.

PMID- 17000982
TI  - CSF neurofilament levels: a potential prognostic marker in Guillain-Barre
      syndrome.
AB  - Long-term morbidity from Guillain-Barre syndrome (GBS) is caused by axonal
      damage. This prospective study demonstrated that neurofilaments (NfHs), a
      biomarker for axonal damage, were of prognostic value in GBS. CSF NfH levels
      correlated with the F score and Medical Research Council summed score and were
      higher in patients with neurophysiologic evidence of axonal degeneration compared
      to those without. Pathologically high CSF NfH levels (>0.73 ng/mL) predicted
      worse motor and functional outcome.

PMID- 17000983
TI  - The challenge of diagnosing ALS in patients with prior poliomyelitis.
AB  - Four patients with postpolio syndrome (PPS) developed ALS. Weakness and atrophy
      started from previously unaffected extremities but, contrary to PPS, spread to
      all muscles leading to death within 0.4 to 8 (mean 3.9) years. Upper motor neuron
      signs were absent in the atrophic limbs. Abundant spontaneous activity and group
      atrophy in newly affected muscles were prominent. ALS can rarely occur in the
      postpolio population starting de novo rather than as evolution of PPS.

PMID- 17000984
TI  - Hypokalemic paralysis due to Gitelman syndrome: a family study.
AB  - Hypokalemic paralysis is rarely seen as the presenting feature in patients with
      Gitelman syndrome. We report a Chinese man who presented with periodic paralysis,
      in whom molecular analysis revealed compound heterozygous inheritance of three
      mutations of the thiazide-sensitive sodium chloride cotransporter. Family history
      revealed intrafamilial variation in phenotypes. Gitelman syndrome should be
      considered as a cause of hypokalemic paralysis, and molecular analysis may help
      establish the diagnosis.

PMID- 17000985
TI  - Botulinum toxin injection for congenital muscular torticollis presenting in
      children and adults.
AB  - Congenital muscular torticollis may present in late childhood or adulthood with
      cervical contractures, limited range of motion, pain, and muscular hypertrophy.
      Seven of eight pediatric and adult patients with congenital muscular torticollis
      were injected with botulinum toxin type A. Only two patients had a modest benefit
      with improved range of motion. Early recognition and treatment of congenital
      muscular torticollis is crucial to prevent subsequent contractures and other
      complications.

PMID- 17000986
TI  - Movement-related cortical activation in familial Parkinson disease.
AB  - We sought to determine whether or not first-degree relatives of patients with
      familial Parkinson disease (FDRs) present impaired movement-related cortical
      activity. We studied 10 familial Parkinson disease subjects, 10 FDRs, and 10
      controls and analyzed event-related mu desynchronization (ERD) and beta
      synchronization. Forty percent FDRs presented reduced premovement mu ERD latency,
      suggesting that premovement cortical activation is impaired in FDRs.

PMID- 17000987
TI  - Subdural hematoma in spontaneous CSF hypovolemia.
AB  - Of 67 consecutive patients with spontaneous CSF hypovolemia (SCH), 11 (16.4%) had
      subdural hematoma (SDH). Patients with SDH were older (p = 0.005), more likely to
      be male (p = 0.035), and displayed longer time to diagnosis of SCH (p = 0.019)
      than those without SDH. All patients with SDH showed the findings of pseudo
      subarachnoid hemorrhage on CT and responded favorably to epidural blood patches
      and neurosurgical drainage.

PMID- 17000988
TI  - Pathologic and physiologic function in the subcortical band of double cortex.
AB  - Double cortex is a neuronal migration disorder, associated with impaired
      cognitive function and seizures, and characterized by a subcortical band of
      neurons. Using functional MRI, we assessed the involvement of the subcortical
      band in language function and with interictal discharges. In both girls assessed,
      language-associated activation was in typical cortical areas, as well as in parts
      of the subcortical band. Interictal discharges were associated with deactivation
      in the subcortical band. This suggests involvement of the subcortical neurons in
      physiologic and pathologic functions.

PMID- 17000989
TI  - A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic
      deletions in SCN1A.
AB  - We examined cases of severe myoclonic epilepsy of infancy (SMEI) for exon
      deletions or duplications within the sodium channel SCN1A gene by multiplex
      ligation-dependent probe amplification. Two of 13 patients (15%) who fulfilled
      the strict clinical definition of SMEI but without SCN1A coding or splicing
      mutations had exonic deletions of SCN1A.

PMID- 17000990
TI  - Peripheral arterial embolism during thrombolysis for stroke.

PMID- 17000991
TI  - Baclofen-induced sexual dysfunction.

PMID- 17000992
TI  - Obstacles to primary stroke prevention in children with sickle cell disease.

PMID- 17000993
TI  - Frequency of migraine attacks following stroke starts to decrease before PFO
      closure.

PMID- 17000994
TI  - Autonomy and ars moriendi.

PMID- 17000995
TI  - Left insular stroke is associated with adverse cardiac outcome.

PMID- 17000996
TI  - Continuous positive airway pressure as treatment for catathrenia (nocturnal
      groaning).

PMID- 17000997
TI  - IM interferon beta-1a delays definite multiple sclerosis 5 years after a first
      demyelinating event.

PMID- 17000998
TI  - Monoclonal antibodies from plants: a new speed record.

PMID- 17000999
TI  - Increased sensitivity after repeated stimulation of residual spatial channels in
      blindsight.
AB  - Lesions of the occipital cortex result in areas of cortical blindness affecting
      the corresponding regions of the patient's visual field. The traditional view is
      that, aside from some spontaneous recovery in the first few months after the
      damage, when acute effects have subsided the areas of blindness are absolute and
      permanent. It has been found, however, that within such field defects some
      residual visual capacities may persist in the absence of acknowledged awareness
      by the subject (blindsight type 1) or impaired awareness (type 2). Neuronal
      pathways mediating blindsight have a specific and narrow spatial and temporal
      bandwidth. A group of cortically blind patients (n = 12) carried out a daily
      detection "training" task over a 3-month period, discriminating grating visual
      stimuli optimally configured for blindsight from homogeneous luminance-matched
      stimuli. No feedback was given during the training. Assessment of training was by
      psychophysical measurements carried out before and after training and included
      detection of a range of spatial frequencies (0.5-7 cycles per degree), contrast
      detection at 1 cycle per degree, clinical perimetry, and subjective estimates of
      visual field defect. The results show that repeated stimulation by appropriate
      visual stimuli can result in improvements in visual sensitivities in the very
      depths of the field defect.

PMID- 17001000
TI  - The age incidence of chronic myeloid leukemia can be explained by a one-mutation
      model.
AB  - Chronic myeloid leukemia (CML) is associated with the Philadelphia chromosome,
      which arises by a reciprocal translocation between chromosomes 9 and 22 and
      harbors the BCR-ABL fusion oncogene. It is unknown whether any other mutations
      are needed for the chronic phase of the disease. The CML incidence increases as a
      function of age with an exponent of approximately 3. A slope of 3 could indicate
      that there are two mutations, in addition to the Philadelphia translocation, that
      have not yet been discovered. In this work, we explore an alternative hypothesis:
      We study a model of cancer initiation requiring only a single mutation. A mutated
      cell has a net reproductive advantage over normal cells and, therefore, might
      give rise to clonal expansion. The cancer is detected with a probability that is
      proportional to the size of the mutated cell clone. This model has three waiting
      times: (i) the time until a mutated cell is produced, (ii) the time of clonal
      expansion, and (iii) the time until the clone is detected. Surprisingly, this
      simple process can give rise to cancer incidence curves with exponents up to 3.
      Therefore, the CML incidence data are consistent with the hypothesis that the
      Philadelphia translocation alone is sufficient to cause chronic phase CML.

PMID- 17001001
TI  - Formation of functional centromeric chromatin is specified epigenetically in
      Candida albicans.
AB  - In the pathogenic yeast Candida albicans, the 3-kb centromeric DNA regions (CEN)
      of each of the eight chromosomes have different and unique DNA sequences. The
      centromeric histone CaCse4p (CENP-A homolog) occurs only within these 3-kb CEN
      regions to form specialized centromeric chromatin. Centromere activity was
      maintained on small chromosome fragments derived in vivo by homologous
      recombination of a native chromosome with linear DNA fragments containing a
      telomere and a selectable marker. An in vivo derived 85-kb truncated chromosome
      containing the 3-kb CEN7 locus on 69 kb of chromosome 7 DNA was stably and
      autonomously maintained in mitosis, indicating that preexisting active CEN
      chromatin remains functional through many generations. This same 85-kb chromosome
      fragment, isolated as naked DNA (devoid of chromatin proteins) from C. albicans
      and reintroduced back into C. albicans cells by standard DNA transformation
      techniques, was unable to reform functional CEN chromatin and was mitotically
      unstable. Comparison of active and inactive CEN chromatin digested with
      micrococcal nuclease revealed that periodic nucleosome arrays are disrupted at
      active centromeres. Chromatin immunoprecipitation with antibodies against CaCse4p
      confirmed that CEN7 introduced into C. albicans cells as naked DNA did not
      recruit CaCse4p or induce its spread to a duplicate region only 7 kb away from
      active CEN7 chromatin. These results indicate that CaCse4p recruitment and
      centromere activation are epigenetically specified and maintained in C. albicans.

PMID- 17001002
TI  - Asymmetric phospholipid distribution drives in vitro reconstituted SNARE
      dependent membrane fusion.
AB  - Insulin-stimulated glucose uptake requires the fusion of GLUT4 transporter
      containing vesicles with the plasma membrane, a process that depends on the SNARE
      (soluble N-ethylmaleimide-sensitive fusion factor attachment receptor) proteins
      VAMP2 (vesicle-associated membrane protein 2) and syntaxin 4 (Stx4)/SNAP23
      (soluble N-ethylmaleimide-sensitive fusion factor attachment protein 23).
      Efficient SNARE-dependent fusion has been shown in many settings in vivo to
      require the generation of both phosphatidylinositol-4,5-bisphosphate (PIP2) and
      phosphatidic acid (PA). Addition of PA to Stx4/SNAP23 vesicles markedly enhanced
      the fusion rate, whereas its addition to VAMP2 vesicles was inhibitory. In
      contrast, addition of PIP2 to Stx4/SNAP23 vesicles inhibited the fusion reaction,
      and its addition to VAMP2 vesicles was stimulatory. The optimal distribution of
      phospholipids was found to trigger the progression from the hemifused state to
      full fusion. These findings reveal an unanticipated dependence of SNARE complex
      mediated fusion on asymmetrically distributed acidic phospholipids and provide
      mechanistic insights into the roles of phospholipase D and PIP kinases in the
      late stages of regulated exocytosis.

PMID- 17001003
TI  - The ferroelectric and cubic phases in BaTiO3 ferroelectrics are also
      antiferroelectric.
AB  - Using quantum mechanics (QM, Density Functional Theory) we show that all four
      phases of barium titanate (BaTiO(3)) have local Ti distortions toward 111 (an
      octahedral face). The stable rhombohedral phase has all distortions in phase
      (ferroelectric, FE), whereas higher temperature phases have antiferroelectric
      coupling (AFE) in one, two, or three dimensions (orthorhombic, tetragonal,
      cubic). This FE-AFE model from QM explains such puzzling aspects of these systems
      as the allowed Raman excitation observed for the cubic phase, the distortions
      toward 111 observed in the cubic phase using x-ray fine structure, the small
      transition entropies, the heavily damped soft phonon modes, and the strong
      diffuse x-ray scattering in all but the rhombohedral phase. In addition, we
      expect to see additional weak Bragg peaks at the face centers of the reciprocal
      lattice for the cubic phase. Similar FE-AFE descriptions are expected to occur
      for other FE materials. Accounting for this FE-AFE nature of these phases is
      expected to be important in accurately simulating the domain wall structures,
      energetics, and dynamics, which in turn may lead to the design of improved
      materials.

PMID- 17001004
TI  - Aging may be a conditional strategic choice and not an inevitable outcome for
      bacteria.
AB  - Aging is known in all organisms that have different somatic and reproductive
      cells or in unicellular organisms that divide asymmetrically. Bacteria that
      divide symmetrically were believed to be immune to natural aging. The
      demonstration of functionally asymmetric division and aging in Escherichia coli
      recently has challenged this belief and led to the suggestion that aging might be
      inevitable for all life forms. We modeled the effects of symmetric and asymmetric
      division in bacteria to examine selective advantages of the alternative
      strategies of division. Aging of cell components was modeled by using a modified
      Leslie matrix framework. The model suggests that asymmetric division accompanied
      by aging and death of some cells results in a higher growth rate but a reduced
      growth yield. Symmetric division with or without gradual replacement of the old
      components, on the other hand, slows down the growth rate but may increase growth
      yield over a wide range of conditions. Thus, aging and immortality can be
      selected under different sets of conditions, and this selection may also lead to
      a tradeoff between growth rate and growth yield.

PMID- 17001005
TI  - Deterministic hydrodynamics: taking blood apart.
AB  - We show the fractionation of whole blood components and isolation of blood plasma
      with no dilution by using a continuous-flow deterministic array that separates
      blood components by their hydrodynamic size, independent of their mass. We use
      the technology we developed of deterministic arrays which separate white blood
      cells, red blood cells, and platelets from blood plasma at flow velocities of
      1,000 microm/sec and volume rates up to 1 microl/min. We verified by flow
      cytometry that an array using focused injection removed 100% of the lymphocytes
      and monocytes from the main red blood cell and platelet stream. Using a second
      design, we demonstrated the separation of blood plasma from the blood cells
      (white, red, and platelets) with virtually no dilution of the plasma and no
      cellular contamination of the plasma.

PMID- 17001006
TI  - Prediction of protein orientation upon immobilization on biological and
      nonbiological surfaces.
AB  - We report on a rapid simulation method for predicting protein orientation on a
      surface based on electrostatic interactions. New methods for predicting protein
      immobilization are needed because of the increasing use of biosensors and protein
      microarrays, two technologies that use protein immobilization onto a solid
      support, and because the orientation of an immobilized protein is important for
      its function. The proposed simulation model is based on the premise that the
      protein interacts with the electric field generated by the surface, and this
      interaction defines the orientation of attachment. Results of this model are in
      agreement with experimental observations of immobilization of mitochondrial
      creatine kinase and type I hexokinase on biological membranes. The advantages of
      our method are that it can be applied to any protein with a known structure; it
      does not require modeling of the surface at atomic resolution and can be run
      relatively quickly on readily available computing resources. Finally, we also
      propose an orientation of membrane-bound cytochrome c, a protein for which the
      membrane orientation has not been unequivocally determined.

PMID- 17001007
TI  - Genome-wide functional analysis of human cell-cycle regulators.
AB  - Human cells have evolved complex signaling networks to coordinate the cell cycle.
      A detailed understanding of the global regulation of this fundamental process
      requires comprehensive identification of the genes and pathways involved in the
      various stages of cell-cycle progression. To this end, we report a genome-wide
      analysis of the human cell cycle, cell size, and proliferation by targeting >95%
      of the protein-coding genes in the human genome using small interfering RNAs
      (siRNAs). Analysis of >2 million images, acquired by quantitative fluorescence
      microscopy, showed that depletion of 1,152 genes strongly affected cell-cycle
      progression. These genes clustered into eight distinct phenotypic categories
      based on phase of arrest, nuclear area, and nuclear morphology. Phase-specific
      networks were built by interrogating knowledge-based and physical interaction
      databases with identified genes. Genome-wide analysis of cell-cycle regulators
      revealed a number of kinase, phosphatase, and proteolytic proteins and also
      suggests that processes thought to regulate G(1)-S phase progression like
      receptor-mediated signaling, nutrient status, and translation also play important
      roles in the regulation of G(2)/M phase transition. Moreover, 15 genes that are
      integral to TNF/NF-kappaB signaling were found to regulate G(2)/M, a previously
      unanticipated role for this pathway. These analyses provide systems-level insight
      into both known and novel genes as well as pathways that regulate cell-cycle
      progression, a number of which may provide new therapeutic approaches for the
      treatment of cancer.

PMID- 17001008
TI  - Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and
      spermiogenesis.
AB  - Besides the established central role of poly(ADP-ribose) polymerase-1 (Parp-1)
      and Parp-2 in the maintenance of genomic integrity, accumulating evidence
      indicates that poly(ADP-ribosyl)ation may modulate epigenetic modifications under
      physiological conditions. Here, we provide in vivo evidence for the pleiotropic
      involvement of Parp-2 in both meiotic and postmeiotic processes. We show that
      Parp-2-deficient mice exhibit severely impaired spermatogenesis, with a defect in
      prophase of meiosis I characterized by massive apoptosis at pachytene and
      metaphase I stages. Although Parp-2(-/-) spermatocytes exhibit normal telomere
      dynamics and normal chromosome synapsis, they display defective meiotic sex
      chromosome inactivation associated with derailed regulation of histone
      acetylation and methylation and up-regulated X- and Y-linked gene expression.
      Furthermore, a drastically reduced number of crossover-associated Mlh1 foci are
      associated with chromosome missegregation at metaphase I. Moreover, Parp-2(-/-)
      spermatids are severely compromised in differentiation and exhibit a marked delay
      in nuclear elongation. Altogether, our findings indicate that, in addition to its
      well known role in DNA repair, Parp-2 exerts essential functions during meiosis I
      and haploid gamete differentiation.

PMID- 17001009
TI  - Identification of class I MHC-associated phosphopeptides as targets for cancer
      immunotherapy.
AB  - Alterations in phosphorylation of cellular proteins are a hallmark of malignant
      transformation. Degradation of these phosphoproteins could generate cancer
      specific class I MHC-associated phosphopeptides recognizable by CD8+ T
      lymphocytes. In a comparative analysis of phosphopeptides presented on the
      surface of melanoma, ovarian carcinoma, and B lymphoblastoid cells, we find 5 of
      36 that are restricted to the solid tumors and common to both cancers.
      Differential presentation of these peptides can result from differential
      phosphorylation of the source proteins. Recognition of the peptides on cancer
      cells by phosphopeptide-specific CD8+ T lymphocytes validates the potential of
      these phosphopeptides as immunotherapeutic targets.

PMID- 17001010
TI  - The surface oxidation potential of human neuromelanin reveals a spherical
      architecture with a pheomelanin core and a eumelanin surface.
AB  - Neuromelanin (NM) isolated from the substantia nigra region of the human brain
      was studied by scanning probe and photoelectron emission microscopies. Atomic
      force microscopy reveals that NM granules are comprised of spherical structures
      with a diameter of approximately 30 nm, similar to that observed for Sepia
      cuttlefish, bovine eye, and human eye and hair melanosomes. Photoelectron
      microscopy images were collected at specific wavelengths of UV light between 248
      and 413 nm, using the spontaneous-emission output from the Duke OK-4 free
      electron laser. Analysis of the data establishes a threshold photoionization
      potential for NM of 4.5 +/- 0.2 eV, which corresponds to an oxidation potential
      of -0.1 +/- 0.2 V vs. the normal hydrogen electrode (NHE). The oxidation
      potential of NM is within experimental error of the oxidation potential measured
      for human eumelanosomes (-0.2 +/- 0.2 V vs. NHE), despite the presence of a
      significant fraction of the red pigment, pheomelanin, which is characterized by a
      higher oxidation potential (+0.5 +/- 0.2 V vs. NHE). Published kinetic studies on
      the early chemical steps of melanogenesis show that in the case of pigments
      containing a mixture of pheomelanin and eumelanin, of which NM is an example,
      pheomelanin formation occurs first with eumelanin formation predominantly
      occurring only after cysteine levels are depleted. Such a kinetic model would
      predict a structural motif with pheomelanin at the core and eumelanin at the
      surface, which is consistent with the measured surface oxidation potential of the
      approximately 30-nm constituents of NM granules.

PMID- 17001011
TI  - Measurement of the mechanical properties of isolated tectorial membrane using
      atomic force microscopy.
AB  - The tectorial membrane (TM) is an extracellular matrix situated over the sensory
      cells of the cochlea. Its strategic location, together with the results of recent
      TM-specific mutation studies, suggests that it has an important role in the
      mechanism by which the cochlea transduces mechanical energy into neural
      excitation. A detailed characterization of TM mechanical properties is
      fundamental to understanding its role in cochlear mechanics. In this work, the
      mechanical properties of the TM are characterized in the radial and longitudinal
      directions using nano- and microindentation experiments conducted by using atomic
      force spectroscopy. We find that the stiffness in the main body region and in the
      spiral limbus attachment zone does not change significantly along the length of
      the cochlea. The main body of the TM is the softest region, whereas the spiral
      limbus attachment zone is stiffer, with the two areas having averaged Young's
      modulus values of 37 +/- 3 and 135 +/- 14 kPa, respectively. By contrast, we find
      that the stiffness of the TM in the region above the outer hair cells (OHCs)
      increases by one order of magnitude in the longitudinal direction, from 24 +/- 4
      kPa in the apical region to 210 +/- 15 kPa at the basilar end of the TM. Scanning
      electron microscopy analysis shows differences in the collagen fiber arrangements
      in the OHC zone of the TM that correspond to the observed variations in
      mechanical properties. The longitudinal increase in TM stiffness is similar to
      that found for the OHC stereocilia, which supports the existence of mechanical
      coupling between these two structures.

PMID- 17001012
TI  - A northern glacial refugium for bank voles (Clethrionomys glareolus).
AB  - There is controversy and uncertainty on how far north there were glacial refugia
      for temperate species during the Pleistocene glaciations and in the extent of the
      contribution of such refugia to present-day populations. We examined these issues
      using phylogeographic analysis of a European woodland mammal, the bank vole
      (Clethrionomys glareolus). A Bayesian coalescence analysis indicates that a bank
      vole population survived the height of the last glaciation (approximately 25,000
      10,000 years B.P.) in the vicinity of the Carpathians, a major central European
      mountain chain well north of the Mediterranean areas typically regarded as
      glacial refugia for temperate species. Parameter estimates from the fitted
      isolation with migration model show that the divergence of the Carpathian
      population started at least 22,000 years ago, and it was likely followed by only
      negligible immigration from adjacent regions, suggesting the persistence of bank
      voles in the Carpathians through the height of the last glaciation. On the
      contrary, there is clear evidence for gene flow out of the Carpathians,
      demonstrating the contribution of the Carpathian population to the colonization
      of Europe after the Pleistocene. These findings are consistent with data from
      animal and plant fossils recovered in the Carpathians and provide the clearest
      phylogeographic evidence to date of a northern glacial refugium for temperate
      species in Europe.

PMID- 17001013
TI  - Hormonal activity of AIMP1/p43 for glucose homeostasis.
AB  - AIMP1/p43 is known as a cytokine working in the control of angiogenesis,
      inflammation, and wound healing. Here we report its enrichment in pancreatic
      alpha cells and glucagon-like hormonal activity. AIMP1 is secreted from the
      pancreas upon glucose starvation. Exogenous infusion of AIMP1 increased plasma
      levels of glucose, glucagon, and fatty acid, and AIMP1-deficient mice showed
      reduced plasma glucose levels compared with the wild-type mice under fasting
      conditions. Thus, AIMP1 plays a glucagon-like role in glucose homeostasis.

PMID- 17001014
TI  - Three restricted forms of Epstein-Barr virus latency counteracting apoptosis in c
      myc-expressing Burkitt lymphoma cells.
AB  - Epstein-Barr virus (EBV), a human herpesvirus, transforms B cell growth in vitro
      through expressing six virus-coded Epstein-Barr nuclear antigens (EBNAs) and two
      latent membrane proteins (LMPs). In many EBV-associated tumors, however, viral
      antigen expression is more restricted, and the aetiological role of the virus is
      unclear. For example, endemic Burkitt lymphoma (BL) classically presents as a
      monoclonal, c-myc-translocation-positive tumor in which every cell carries EBV as
      an EBNA1-only (Latency I) infection; such homogeneity among EBV-positive cells,
      and the lack of EBV-negative comparators, hampers attempts to understand EBV's
      role in BL pathogenesis. Here, we describe an endemic BL that was unusually
      heterogeneous at the single-cell level and, in early passage culture, yielded a
      range of cellular clones, all with the same c-myc translocation but differing in
      EBV status. Rare EBV-negative cells were isolated alongside EBV-positive cells
      displaying one of three forms of restricted latency: (i) conventional Latency I
      expressing EBNA1 only from a WT virus genome, (ii) Wp-restricted latency
      expressing EBNAs 1, 3A, 3B, 3C, and -LP only from an EBNA2-deleted genome, and
      (iii) a previously undescribed EBNA2(+)/LMP1(-) latency in which all six EBNAs
      are expressed again in the absence of the LMPs. Interclonal comparisons showed
      that each form of EBV infection was associated with a specific degree of
      protection from apoptosis. Our work suggests that EBV acts as an antiapoptotic
      rather than a growth-promoting agent in BL by selecting among three
      transcriptional programs, all of which, unlike the full virus growth-transforming
      program, remain compatible with high c-myc expression.

PMID- 17001015
TI  - Preferential transfer of the complete glycan is determined by the
      oligosaccharyltransferase complex and not by the catalytic subunit.
AB  - Most eukaryotic cells show a strong preference for the transfer in vivo and in
      vitro of the largest dolichol-P-P-linked glycan (Glc(3)Man(9)GlcNAc(2)) to
      protein chains over that of biosynthetic intermediates that lack the full
      complement of glucose units. The oligosaccharyltransferase (OST) is a multimeric
      complex containing eight different proteins, one of which (Stt3p) is the
      catalytic subunit. Trypanosomatid protozoa lack an OST complex and express only
      this last protein. Contrary to the OST complex from most eukaryotic cells, the
      Stt3p subunit of these parasites transfers in cell-free assays glycans with Man(7
      9)GlcNAc(2) and Glc(1-3)Man(9)GlcNAc(2) compositions at the same rate. We have
      replaced Saccharomyces cerevisiae Stt3p by the Trypanosoma cruzi homologue and
      found that the complex that is formed preferentially transfers the complete
      glycan both in vivo and in vitro. Thus, preference for Glc(3)Man(9)GlcNAc(2) is a
      feature that is determined by the complex and not by the catalytic subunit.

PMID- 17001016
TI  - Detoxification of superoxide without production of H2O2: antioxidant activity of
      superoxide reductase complexed with ferrocyanide.
AB  - The superoxide radical O(2)(-.) is a toxic by-product of oxygen metabolism. Two
      O(2)(-.) detoxifying enzymes have been described so far, superoxide dismutase and
      superoxide reductase (SOR), both forming H2O2 as a reaction product. Recently,
      the SOR active site, a ferrous iron in a [Fe(2+) (N-His)(4) (S-Cys)]
      pentacoordination, was shown to have the ability to form a complex with the
      organometallic compound ferrocyanide. Here, we have investigated in detail the
      reactivity of the SOR-ferrocyanide complex with O(2)(-.) by pulse and gamma-ray
      radiolysis, infrared, and UV-visible spectroscopies. The complex reacts very
      efficiently with O(2)(-.). However, the presence of the ferrocyanide adduct
      markedly modifies the reaction mechanism of SOR, with the formation of transient
      intermediates different from those observed for SOR alone. A one-electron redox
      chemistry appears to be carried out by the ferrocyanide moiety of the complex,
      whereas the SOR iron site remains in the reduced state. Surprisingly, the toxic
      H2O2 species is no longer the reaction product. Accordingly, in vivo experiments
      showed that formation of the SOR-ferrocyanide complex increased the antioxidant
      capabilities of SOR expressed in an Escherichia coli sodA sodB recA mutant
      strain. Altogether, these data describe an unprecedented O(2)(-.) detoxification
      activity, catalyzed by the SOR-ferrocyanide complex, which does not conduct to
      the production of the toxic H2O2 species.

PMID- 17001017
TI  - A theory for the atmospheric energy spectrum: depth-limited temperature anomalies
      at the tropopause.
AB  - The horizontal spectra of atmospheric wind and temperature at the tropopause have
      a steep -3 slope at synoptic scales, but transition to -5/3 at wavelengths of the
      order of 500-1,000 km [Nastrom, G. D. & Gage, K. S. (1985) J. Atmos. Sci. 42, 950
      960]. Here we demonstrate that a model that assumes zero potential vorticity and
      constant stratification N over a finite-depth H in the troposphere exhibits the
      same type of spectra. In this model, temperature perturbations generated at the
      planetary scale excite a direct cascade of energy with a slope of -3 at large
      scales, -5/3 at small scales, and a transition near horizontal wavenumber k(t) =
      f/NH, where f is the Coriolis parameter. Ballpark atmospheric estimates for N, f,
      and H give a transition wavenumber near that observed, and numerical simulations
      of the previously undescribed model verify the expected behavior. Despite its
      simplicity, the model is consistent with a number of perplexing features in the
      observations and demonstrates that a complete theory for mesoscale dynamics must
      take temperature advection at boundaries into account.

PMID- 17001019
TI  - Major ongoing stroke trials.

PMID- 17001018
TI  - Global temperature change.
AB  - Global surface temperature has increased approximately 0.2 degrees C per decade
      in the past 30 years, similar to the warming rate predicted in the 1980s in
      initial global climate model simulations with transient greenhouse gas changes.
      Warming is larger in the Western Equatorial Pacific than in the Eastern
      Equatorial Pacific over the past century, and we suggest that the increased West
      East temperature gradient may have increased the likelihood of strong El Ninos,
      such as those of 1983 and 1998. Comparison of measured sea surface temperatures
      in the Western Pacific with paleoclimate data suggests that this critical ocean
      region, and probably the planet as a whole, is approximately as warm now as at
      the Holocene maximum and within approximately 1 degrees C of the maximum
      temperature of the past million years. We conclude that global warming of more
      than approximately 1 degrees C, relative to 2000, will constitute "dangerous"
      climate change as judged from likely effects on sea level and extermination of
      species.

PMID- 17001020
TI  - Structural neuroimaging in geriatric psychiatry.

PMID- 17001021
TI  - Structural neuroimaging research methods in geriatric depression.
AB  - Geriatric depression consists of complex and heterogeneous behaviors unlikely to
      be caused by a single brain lesion. However, there is evidence that abnormalities
      in specific brain structures and their interconnections confer vulnerability to
      the development of late-life depression. Structural magnetic resonance imaging
      methods can be used to identify and quantify brain abnormalities predisposing to
      geriatric depression and in prediction of treatment response. This article
      reviews several techniques, including morphometric approaches, study of white
      matter hyperintensities, diffusion tensor imaging, magnetization transfer
      imaging, t2 relaxography, and spectroscopy, that have been used to examine these
      brain abnormalities with a focus on the type of information obtained by each
      method as well as each method's limitations. The authors argue that the available
      methods provide complementary information and that, when combined judiciously,
      can increase the knowledge gained from neuroimaging findings and conceptually
      advance the field of geriatric depression.

PMID- 17001022
TI  - The relationship between frontal gray matter volume and cognition varies across
      the healthy adult lifespan.
AB  - OBJECTIVE: Age-associated decline in gray matter brain volume and cognitive
      function in healthy adults has been reported in the literature. The goal of the
      current study is to examine the relationship between age-related changes in
      regional gray matter volumes and cognitive function in a large, cross-sectional
      sample of healthy adults across the lifespan. METHODS: Magnetic resonance imaging
      and cognitive assessment were conducted on 148 adults aged 21-76 years. Multiple
      regression analyses examining the effect of age were performed on magnetic
      resonance image-derived gray matter brain volumes and standardized cognitive
      summary scores of attention and executive function. Regression was also performed
      to test the effect of age, gray matter volumes, and their interaction on the
      prediction of cognitive performance. RESULTS: Age significantly predicted
      performance on tests of attention (F [1, 146]=50.97, p <0.01, R2=0.26) and
      executive function (F [1, 146]=126.19, p <0.01, R2=0.46) and gray matter volumes
      for frontal subregions (lateral, medial, orbital), hippocampus, amygdala, and
      putamen (F [2, 145]=45.34-23.96, p <0.01-0.02). Lateral frontal (beta=-1.53, t=
      2.16, df=131, p <0.03) and orbital frontal (beta=1.24, t=2.08, df=131, p <0.04)
      regions significantly predicted performance on tests of attention. Lateral
      frontal (beta=-1.69, t=-2.83, df=131, p <0.01) and the interaction between age
      and lateral frontal volume (beta=3.76, t=2.49, df=131, p <0.02) significantly
      predicted executive function. CONCLUSIONS: The findings confirm age-associated
      decline in cognitive function and gray matter volumes, particularly in anterior
      cortical brain regions. Furthermore, the association between lateral frontal gray
      matter volume and the ability to successfully plan, organize, and execute
      strategies varies as a function of age across the healthy adult lifespan.

PMID- 17001023
TI  - White matter hyperintensities rather than lacunar infarcts are associated with
      depressive symptoms in older people: the LADIS study.
AB  - OBJECTIVE: Both white matter hyperintensities (WMH) and lacunar infarcts have
      been associated with the development of depression in older subjects, although
      the relative importance of the two and the influence of lesion location and
      concomitant vascular disease are unclear. This study investigates the
      relationship between location and burden of WMH and lacunes on depressive
      features in older people. METHOD: In a pan-European multicenter study of 626
      older subjects, the authors examined the relationship between regional magnetic
      resonance imaging white matter hyperintensities, number of lacunar infarcts,
      depressive symptoms as assessed by the 15-item geriatric depression scale (GDS),
      cognitive status (Mini-Mental Status Examination), hypertension, and self
      perceived health quality of life (QoL). RESULTS: The authors found depressive
      symptoms to be correlated with WMH rating in the frontal (N=626; Spearman's
      rho=0.161, p <0.001) and temporal (rho=0.14, p <0.001) but not occipitoparietal
      region (rho=0.07, p=0.07). Basal ganglia lacunes were only weakly correlated with
      GDS (rho=0.09, p=0.03), and lacunes in other regions showed no association. In a
      ordinal logistic regression model (controlling for QoL, Mini-Mental Status
      Examination, age, and with an interaction between WMH and hypertension), temporal
      WMH in the absence of hypertension independently predicted GDS, whereas neither
      history of stroke nor number of lacunar infarcts did. The authors compared left-
      versus right-sided WMH and found no effect of laterality on depressive symptoms.
      CONCLUSIONS: The results suggest that in this population of nondisabled older
      people, WMH have a greater influence on depressive symptoms than infarcts.

PMID- 17001024
TI  - Progression of white matter hyperintensities in Alzheimer disease, dementia with
      lewy bodies, and Parkinson disease dementia: a comparison with normal aging.
AB  - OBJECTIVE: The objective of this study was to investigate cross-sectional and
      longitudinal white matter hyperintensity (WMH) changes in older subjects with
      clinically diagnosed dementia. METHODS: Fluid-attenuated inversion recovery
      images were acquired one year apart in subjects with dementia with Lewy bodies
      (DLB), Parkinson disease dementia (PDD), Alzheimer disease (AD), and also healthy
      elderly comparison subjects. WMH volume was quantified using an automated
      technique. RESULTS: Baseline WMH (as a percent of brain volume) was significantly
      greater compared with healthy subjects (N=33, geometric mean WMH: 0.4%) in
      subjects with AD (N=23 [1.3%], analysis of variance post hoc p <0.001) but not
      PDD (N=13 [0.6%]) or DLB (N=14 [0.4%]). Increase in WMH volume (as a percent of
      brain volume) was not significantly different (Kruskal-Wallis p=0.4) between
      groups (AD median change: 0.08%; DLB: 0.025%; PDD: 0.07%, healthy: 0.02%).
      Severity of baseline WMH, rather than diagnosis or severity of dementia, was a
      significant predictor of lesion progression. Rate of change of WMH had no
      association with change in global cognitive performance. CONCLUSIONS: Significant
      WMH progression occurs in degenerative dementias with rates influenced by
      severity of lesions at baseline rather than dementia type or cognitive decline.

PMID- 17001025
TI  - Sleep: a marker of physical and mental health in the elderly.
AB  - OBJECTIVE: The objective of this study was to determine the occurrence and
      recognition of common sleep-related problems and their relationship to health
      related quality-of-life measures in the elderly. METHOD: A total of 1,503
      participants with a mean age of 75.5 (+/- 6.8, range: 62-100) years from 11
      primary care sites serving primarily elderly patients were interviewed. Subjects
      completed a five-item sleep questionnaire and the SF-12. A Physical Component
      Summary (PCS-12) and Mental Component Summary (MCS-12) score was calculated. A
      systematic medical chart review was conducted to determine whether sleep problems
      were identified by the healthcare providers. RESULTS: A total of 68.9% of
      patients reported at least one sleep complaint and 40% had two or more.
      Participants most commonly endorsed (45%) that they had "difficulty falling
      asleep, staying asleep, or being able to sleep." The number and type of sleep
      problems endorsed was associated with both physical and mental health quality-of
      life status. Excessive daytime sleepiness was the best predictor of poor mental
      and physical health-related quality of life. Even when all five sleep questions
      were endorsed, a sleep complaint was only reported in the chart 19.2% of the
      time. CONCLUSIONS: When elicited, sleep complaints predicted the general physical
      and mental health-related quality-of-life status in elderly populations with
      comorbid medical and mental illnesses. Yet, questions regarding sleep are not an
      integral component of most clinical evaluations. Given the growing evidence of a
      relationship between sleep and health, identification of sleep disorders could
      lead to improved management of common age-related chronic illnesses and quality
      of life of elderly patients.

PMID- 17001026
TI  - Geriatric heart failure, depression, and nursing home admission: an observational
      study using propensity score analysis.
AB  - OBJECTIVE: Heart failure (HF) and depression are both common in older adults, and
      the presence of depression is known to worsen HF outcomes. For community-dwelling
      older adults, admission to a nursing home (NH) is associated with loss of
      independent living and poor outcomes. The objective of this study was to examine
      the effect of depression on NH admission for older adults with HF. METHODS: Using
      the 2001-2003 National Hospital Discharge Survey datasets, the authors identified
      all community-dwelling older adults who were discharged alive with a primary
      discharge diagnosis of HF. The authors then identified those with a secondary
      diagnosis of depression. Using a multivariable logistic regression model, the
      authors then determined probability or propensity to have depression for each
      patient. The authors used propensity scores for depression to match all 680
      depressed patients with 2,040 nondepressed patients. Finally, the authors
      estimated the association between depression and NH admission using bivariate and
      multivariable logistic regression analyses. RESULTS: Patients had a mean (+/-
      standard deviation) age of 79 (+/- 8) years, 72% were women, and 9% were blacks.
      Compared with 17% nondepressed patients, 25% depressed patients were discharged
      to a NH. Depression was associated with 50% increased risk of NH admission
      (unadjusted relative risk [RR]: 1.50; 95% confidence interval [CI]: 1.28-1.74).
      The association became somewhat stronger after multivariable adjustment for
      various demographic and care covariates (adjusted RR: 1.60; 95% CI: 1.35-1.68).
      CONCLUSION: In ambulatory older adults hospitalized with HF, a secondary
      diagnosis of depression was associated with a significant increased risk of NH
      admission.

PMID- 17001027
TI  - Depression in assisted living is common and related to physical burden.
AB  - OBJECTIVE: The objective of this study was to obtain a direct estimate of the
      prevalence of depression, its associated factors, and rates of treatment among
      residents of assisted living (AL) facilities in central Maryland. METHOD: One
      hundred ninety-six AL residents were recruited from 22 (10 large and 12 small)
      randomly selected AL facilities in the city of Baltimore and seven Maryland
      counties. Chart review, staff and family history, comprehensive in-person
      resident evaluation, and the Cornell Scale for Depression in Dementia (CSDD) were
      administered by an experienced team of geriatric psychiatry clinicians. Those
      scoring >7 on the CSDD, a cut point repeatedly associated with poor outcomes,
      were considered clinically depressed. RESULTS: Participants had an average age of
      86 years, most were female and widowed, and 68% met consensus criteria for
      dementia. Twenty-four percent (47 of 196) of the sample was depressed. In
      bivariate analyses, depression was significantly related to medical comorbidity,
      need for activities of daily living (ADLs) assistance, more days spent in bed,
      and less participation in organized activities. After controlling for pertinent
      covariates in a regression model, only need for ADL assistance remained
      significantly associated with depression. Forty-three percent of those currently
      depressed were receiving antidepressants and were more likely to receive them if
      they lived in a large AL facility. Sixty percent of depressed residents had no
      regular source of psychiatric care. CONCLUSIONS: In the first clinical study
      implemented by geriatric psychiatry professionals in AL, depression was found to
      be common, undertreated, and related to physical burden. AL is a rapidly growing
      segment of long-term care and represents an important setting in which to find
      and treat serious depression.

PMID- 17001028
TI  - Gender disparities in the treatment of late-life depression: qualitative and
      quantitative findings from the IMPACT trial.
AB  - OBJECTIVES: The objectives of this study were to examine gender differences in
      recruitment, depression presentation, and depression treatment history in a large
      effectiveness trial; and to use qualitative data to generate hypotheses about
      reasons for observed gender differences. METHODS: Data from IMPACT, a multisite
      trial of a disease management program for late-life depression in primary care
      were used to examine gender differences quantitatively. Qualitative interviews
      were conducted with 30 key informants from IMPACT (referring physicians,
      depression care managers, and study recruiters) to learn more about challenges in
      recruiting and treating depressed older men and then analyzed thematically.
      RESULTS: Compared with older women, older men were significantly less likely to
      be referred to IMPACT, to endorse core depressive symptoms, and to have received
      prior depression treatment. Gender differences in prior depression treatment
      persisted after adjustment for covariates. Qualitative themes identified as
      important contributors to gender disparities included 1) how men experience and
      express their depression, 2) traditional masculine values, and 3) the stigma of
      chronic mental illness. CONCLUSION: This study provides further evidence of the
      gender gap in depression care, identifies possible contributing factors, and
      suggests avenues for future research.

PMID- 17001029
TI  - Cognitive impairment of acute onset in the Consortium to Investigate Vascular
      Impairment of Cognition (CIVIC) study: occurrence, correlates, and outcomes.
AB  - OBJECTIVE: Having demonstrated that dementia of acute onset represents a distinct
      syndrome with distinct outcomes, the authors investigated whether similar
      attributes describe cognitive impairment of acute onset (CIAO). METHODS: The
      authors conducted a secondary analysis of the Consortium to Investigate Vascular
      Impairment of Cognition study. RESULTS: Ninety patients met our criteria for
      CIAO. Compared with cognitive impairment of gradual onset, CIAO was associated
      with vascular features (odds ratio [OR]: 12.3, 95% confidence interval [CI]: 3.2
      47.9), dementias other than Alzheimer disease (OR: 6.5, 95% CI: 2.1-20.8), and
      decreased survival (hazard ratio: 2.8, 95% CI: 1.6-4.6). CONCLUSIONS: Patients
      with CIAO are clinically identifiable and have distinct outcomes.

PMID- 17001030
TI  - Crystal structures of the DNA-binding domain of Escherichia coli proline
      utilization A flavoprotein and analysis of the role of Lys9 in DNA recognition.
AB  - PutA (proline utilization A) from Escherichia coli is a 1320-amino-acid residue
      protein that is both a bifunctional proline catabolic enzyme and an autogenous
      transcriptional repressor. Here, we report the first crystal structure of a PutA
      DNA-binding domain along with functional analysis of a mutant PutA defective in
      DNA binding. Crystals were grown using a polypeptide corresponding to residues 1
      52 of E. coli PutA (PutA52). The 2.1 Angstrom resolution structure of PutA52
      mutant Lys9Met was determined using Se-Met MAD phasing, and the structure of
      native PutA52 was solved at 1.9 Angstrom resolution using molecular replacement.
      Residues 3-46 form a ribbon-helix-helix (RHH) substructure, thus establishing
      PutA as the largest protein to contain an RHH domain. The PutA RHH domain forms
      the intertwined dimer with tightly packed hydrophobic core that is characteristic
      of the RHH family. The structures were used to examine the three-dimensional
      context of residues conserved in PutA RHH domains. Homology modeling suggests
      that Lys9 and Thr5 contact DNA bases through the major groove, while Arg15,
      Thr28, and His30 may interact with the phosphate backbone. Lys9 is shown to be
      essential for specific recognition of put control DNA using gel shift analysis of
      the Lys9Met mutant of full-length PutA. Lys9 is disordered in the PutA52
      structure, which implies an induced-fit binding mechanism in which the side chain
      of Lys9 becomes ordered through interaction with DNA. These results provide new
      insights into the structural basis of DNA recognition by PutA and reveal three
      dimensional structural details of the PutA dimer interface.

PMID- 17001031
TI  - A fast method for the determination of fractional contributions to solvation in
      proteins.
AB  - A fast method for the calculation of residue contributions to protein solvation
      is presented. The approach uses the exposed polar and apolar surface of protein
      residues and has been parametrized from the fractional contributions to solvation
      determined from linear response theory coupled to molecular dynamics simulations.
      Application of the method to a large subset of proteins taken from the Protein
      Data Bank allowed us to compute the expected fractional solvation of residues.
      This information is used to discuss when a residue or a group of residues
      presents an uncommon solvation profile.

PMID- 17001032
TI  - Prediction of residues in discontinuous B-cell epitopes using protein 3D
      structures.
AB  - Discovery of discontinuous B-cell epitopes is a major challenge in vaccine
      design. Previous epitope prediction methods have mostly been based on protein
      sequences and are not very effective. Here, we present DiscoTope, a novel method
      for discontinuous epitope prediction that uses protein three-dimensional
      structural data. The method is based on amino acid statistics, spatial
      information, and surface accessibility in a compiled data set of discontinuous
      epitopes determined by X-ray crystallography of antibody/antigen protein
      complexes. DiscoTope is the first method to focus explicitly on discontinuous
      epitopes. We show that the new structure-based method has a better performance
      for predicting residues of discontinuous epitopes than methods based solely on
      sequence information, and that it can successfully predict epitope residues that
      have been identified by different techniques. DiscoTope detects 15.5% of residues
      located in discontinuous epitopes with a specificity of 95%. At this level of
      specificity, the conventional Parker hydrophilicity scale for predicting linear B
      cell epitopes identifies only 11.0% of residues located in discontinuous
      epitopes. Predictions by the DiscoTope method can guide experimental epitope
      mapping in both rational vaccine design and development of diagnostic tools, and
      may lead to more efficient epitope identification.

PMID- 17001033
TI  - Stabilization of a binary protein complex by intein-mediated cyclization.
AB  - The study of protein-protein interactions can be hampered by the instability of
      one or more of the protein complex components. In this study, we showed that
      intein-mediated cyclization can be used to engineer an artificial intramolecular
      cyclic protein complex between two interacting proteins: the largely unstable LIM
      only protein 4 (LMO4) and an unstructured domain of LIM domain binding protein 1
      (ldb1). The X-ray structure of the cyclic complex is identical to noncyclized
      versions of the complex. Chemical and thermal denaturation assays using intrinsic
      tryptophan fluorescence and dynamic light scattering were used to compare the
      relative stabilities of the cyclized complex, the intermolecular (or free)
      complex, and two linear versions of the intramolecular complex (in which the
      interacting domains of LMO4 and ldb1 were fused, via a flexible linker, in either
      orientation). In terms of resistance to denaturation, the cyclic complex is the
      most stable variant and the intermolecular complex is the least stable; however,
      the two linear intramolecular variants show significant differences in stability.
      These differences appear to be related to the relative contact order (the average
      distance in sequence between residues that make contacts within a structure) of
      key binding residues at the interface of the two proteins. Thus, the restriction
      of the more stable component of a complex may enhance stability to a greater
      extent than restraining less stable components.

PMID- 17001034
TI  - Folding and misfolding mechanisms of the p53 DNA binding domain at physiological
      temperature.
AB  - p53 modulates a large number of cellular response pathways and is critical for
      the prevention of cancer. Wild-type p53, as well as tumorigenic mutants, exhibits
      the singular property of spontaneously losing DNA binding activity at 37 degrees
      C. To understand the molecular basis for this effect, we examine the folding
      mechanism of the p53 DNA binding domain (DBD) at elevated temperatures. Folding
      kinetics do not change appreciably from 5 degrees C to 35 degrees C. DBD
      therefore folds by the same two-channel mechanism at physiological temperature as
      it does at 10 degrees C. Unfolding rates, however, accelerate by 10,000-fold.
      Elevated temperatures thus dramatically increase the frequency of cycling between
      folded and unfolded states. The results suggest that function is lost because a
      fraction of molecules become trapped in misfolded conformations with each folding
      unfolding cycle. In addition, at 37 degrees C, the equilibrium stabilities of the
      off-pathway species are predicted to rival that of the native state, particularly
      in the case of destabilized mutants. We propose that it is the presence of these
      misfolded species, which can aggregate in vitro and may be degraded in the cell,
      that leads to p53 inactivation.

PMID- 17001035
TI  - The crystal structure of the E. coli stress protein YciF.
AB  - YciF is a protein that is up-regulated when bacteria experience stress
      conditions, and is highly conserved in a range of bacterial species. YciF has no
      known structure or biochemical function. To learn more about its potential
      molecular function and its role in the bacterial stress response, we solved the
      crystal structure of YciF at 2.0 Angstrom resolution by the multiple wavelength
      anomalous diffraction (MAD) technique. YciF is a dimer in solution, and forms a
      homodimer in the crystal asymmetric unit. The two monomers form a dimer with a
      molecular twofold axis, with a significant burial of solvent-accessible surface
      area. The protein is an all-alpha protein composed of five helices: a four-helix
      bundle, and a short additional helix at the dimer interface. The protein is
      structurally similar to portions of the diiron-containing proteins, rubrerythrin
      and the Bacillus anthracis Dlp-2.

PMID- 17001036
TI  - Determination of the human type I interferon receptor binding site on human
      interferon-alpha2 by cross saturation and an NMR-based model of the complex.
AB  - Type I interferons (IFNs) are a family of homologous helical cytokines that
      exhibit pleiotropic effects on a wide variety of cell types, including antiviral
      activity and antibacterial, antiprozoal, immunomodulatory, and cell growth
      regulatory functions. Consequently, IFNs are the human proteins most widely used
      in the treatment of several kinds of cancer, hepatitis C, and multiple sclerosis.
      All type I IFNs bind to a cell surface receptor consisting of two subunits,
      IFNAR1 and IFNAR2, associating upon binding of interferon. The structure of the
      extracellular domain of IFNAR2 (R2-EC) was solved recently. Here we study the
      complex and the binding interface of IFNalpha2 with R2-EC using multidimensional
      NMR techniques. NMR shows that IFNalpha2 does not undergo significant structural
      changes upon binding to its receptor, suggesting a lock-and-key mechanism for
      binding. Cross saturation experiments were used to determine the receptor binding
      site upon IFNalpha2. The NMR data and previously published mutagenesis data were
      used to derive a docking model of the complex with an RMSD of 1 Angstrom, and its
      well-defined orientation between IFNalpha2 and R2-EC and the structural quality
      greatly improve upon previously suggested models. The relative ligand-receptor
      orientation is believed to be important for interferon signaling and possibly one
      of the parameters that distinguish the different IFN I subtypes. This structural
      information provides important insight into interferon signaling processes and
      may allow improvement in the development of therapeutically used IFNs and IFN
      like molecules.

PMID- 17001037
TI  - Insights into the architecture of the Ure2p yeast protein assemblies from helical
      twisted fibrils.
AB  - The protein Ure2 from baker's yeast is associated with a heritable and
      transmissible phenotypic change in the yeast Saccharomyces cerevisiae. Such prion
      properties are thought to arise from the fact that Ure2p is able to self-assemble
      into insoluble fibrils. Assemblies of Ure2p are composed of full-length proteins
      in which the structure of the globular, functional, C-terminal domain is
      retained. We have carried out structural studies on full-length, wild-type Ure2p
      fibrils with a regularly twisted morphology. Using electron microscopy and cryo
      electron microscopy with image analysis we show high-resolution images of the
      twisted filaments revealing details within the fibrillar structure. We examine
      these details in light of recent proposed models and discuss how this new
      information contributes to an understanding of the architecture of Ure2p yeast
      prion fibrils.

PMID- 17001038
TI  - NMR characterizations of an amyloidogenic conformational ensemble of the PI3K SH3
      domain.
AB  - Amyloid formation is associated with structural changes of native polypeptides to
      monomeric intermediate states and their self-assembly into insoluble aggregates.
      Characterizations of the amyloidogenic intermediate state are, therefore, of
      great importance in understanding the early stage of amyloidogenesis. Here, we
      present NMR investigations of the structural and dynamic properties of the acid
      unfolded amyloidogenic intermediate state of the phosphatidylinositol 3-kinase
      (PI3K) SH3 domain--a model peptide. The monomeric amyloidogenic state of the SH3
      domain studied at pH 2.0 (35 degrees C) was shown to be substantially disordered
      with no secondary structural preferences. (15)N NMR relaxation experiments
      indicated that the unfolded polypeptide is highly flexible on a subnanosecond
      timescale when observed under the amyloidogenic condition (pH 2.0, 35 degrees C).
      However, more restricted motions were detected in residues located primarily in
      the beta-strands as well as in a loop in the native fold. In addition, nonnative
      long-range interactions were observed between the residues with the reduced
      flexibility by paramagnetic relaxation enhancement (PRE) experiments. These
      indicate that the acid-unfolded state of the SH3 domain adopts a partly folded
      conformation through nonnative long-range contacts between the dynamically
      restricted residues at the amyloid-forming condition.

PMID- 17001039
TI  - A Consensus Data Mining secondary structure prediction by combining GOR V and
      Fragment Database Mining.
AB  - The major aim of tertiary structure prediction is to obtain protein models with
      the highest possible accuracy. Fold recognition, homology modeling, and de novo
      prediction methods typically use predicted secondary structures as input, and all
      of these methods may significantly benefit from more accurate secondary structure
      predictions. Although there are many different secondary structure prediction
      methods available in the literature, their cross-validated prediction accuracy is
      generally <80%. In order to increase the prediction accuracy, we developed a
      novel hybrid algorithm called Consensus Data Mining (CDM) that combines our two
      previous successful methods: (1) Fragment Database Mining (FDM), which exploits
      the Protein Data Bank structures, and (2) GOR V, which is based on information
      theory, Bayesian statistics, and multiple sequence alignments (MSA). In CDM, the
      target sequence is dissected into smaller fragments that are compared with
      fragments obtained from related sequences in the PDB. For fragments with a
      sequence identity above a certain sequence identity threshold, the FDM method is
      applied for the prediction. The remainder of the fragments are predicted by GOR
      V. The results of the CDM are provided as a function of the upper sequence
      identities of aligned fragments and the sequence identity threshold. We observe
      that the value 50% is the optimum sequence identity threshold, and that the
      accuracy of the CDM method measured by Q(3) ranges from 67.5% to 93.2%, depending
      on the availability of known structural fragments with sufficiently high sequence
      identity. As the Protein Data Bank grows, it is anticipated that this consensus
      method will improve because it will rely more upon the structural fragments.

PMID- 17001040
TI  - Finding the way--meeting the needs of adults with childhood-acquired illnesses.

PMID- 17001041
TI  - HIV/TB co-infections rising.

PMID- 17001042
TI  - Canada falters on promise of AIDS drugs for Africa.

PMID- 17001043
TI  - Microbicide update.

PMID- 17001044
TI  - "Damage control" surgery techniques used on soldiers.

PMID- 17001045
TI  - Changing family practice.

PMID- 17001046
TI  - UK needs 10,000 more therapists.

PMID- 17001047
TI  - Government health care outlays fall below OECD average.

PMID- 17001048
TI  - How should developing countries manage diabetes?

PMID- 17001049
TI  - Recurrent meningitis in a child due to an occult spinal lesion.

PMID- 17001050
TI  - Atraumatic fracture of proximal first phalanx.

PMID- 17001051
TI  - Gastroenteric duplication cyst.

PMID- 17001052
TI  - Bowen disease.

PMID- 17001053
TI  - Highlights of the National Advisory Committee on Immunization statement on
      influenza for the 2006-2007 season.

PMID- 17001054
TI  - Proton pump inhibitor use and risk of community-acquired Clostridium difficile
      associated disease defined by prescription for oral vancomycin therapy.
AB  - BACKGROUND: The association between the use of proton pump inhibitors and the
      risk of Clostridium difficile-associated disease (CDAD) is controversial. In this
      study we re-examined a previously reported association between the use of proton
      pump inhibitors and the development of community-acquired CDAD, this time using
      an alternative case definition of the disease. METHODS: We performed a case
      control study of community-acquired CDAD using a United Kingdom clinical research
      database. Patients receiving oral vancomycin therapy were identified as having
      CDAD, the only indication for this drug. Each case subject was matched with up to
      10 control subjects. Neither the cases nor the controls had been admitted to
      hospital in the year before the date of the vancomycin prescription (index date).
      Conditional logistic regression analysis was used to adjust for key covariates.
      RESULTS: We identified 317 cases of community-acquired CDAD treated with oral
      vancomycin therapy and 3167 matched control subjects. Exposure to a proton pump
      inhibitor in the 90 days before the index date was associated with an increased
      risk of CDAD (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.3-5.2).
      Antibiotic exposure in the 90 days before the index date was also a significant
      risk factor for community-acquired CDAD (OR 8.2, 95% CI 6.1- 11.0), even though
      45% of the case subjects had not received a prescription for an antibiotic during
      that period. Certain comorbidities, in particular renal failure, inflammatory
      bowel disease and malignant disease, as well as prior methicillin-resistant
      Staphylococcus aureus infection, were also associated with an increased risk.
      INTERPRETATION: Proton pump inhibitor use was associated with an increased risk
      of community-acquired CDAD, when cases were defined by receipt of prescription
      for oral vancomycin therapy. Prior antibiotic exposure was also a significant
      risk factor, but a significant proportion of the patients with community-acquired
      CDAD had no such exposure.

PMID- 17001055
TI  - The impact of physician training and experience on the survival of patients with
      active tuberculosis.
AB  - BACKGROUND: Physician training and experience may be important factors
      influencing treatment outcomes of patients with tuberculosis. We conducted an
      analysis to evaluate physician and patient characteristics and their association
      with the rate of death among tuberculosis patients. METHODS: We retrospectively
      reviewed all reported cases of active tuberculosis in Toronto between July 1,
      1999, and June 30, 2002. We obtained extensive clinical data on cases as well as
      information on the training and clinical experience of treating physicians. We
      subsequently identified factors associated with patient mortality in a survival
      analysis. RESULTS: In a multivariable Cox regression analysis involving 1154
      patients, factors associated with all-cause mortality included patient age (in
      years) (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.04-1.07, p <
      0.001), use of directly observed therapy (HR 0.22, CI 0.13-0.39, p < 0.001),
      receipt of care from a physician experienced with tuberculosis (per case managed
      per year) (HR 0.98, CI 0.97-0.99; p = 0.01) and admission to hospital during the
      course of treatment (HR 15.44, CI 7.06-33.76, p < 0.001). Factors that were not
      associated with patient survival included whether the physician graduated from a
      foreign medical school, the physician's medical specialty and the number of years
      in clinical practice. INTERPRETATION: Physician experience with tuberculosis and
      use of directly observed therapy positively influenced the survival of patients
      with active tuberculosis in our setting.

PMID- 17001056
TI  - Proton pump inhibitors and the risk of Clostridium difficile-associated disease:
      further evidence from the community.

PMID- 17001057
TI  - Physician experience, public health and the management of tuberculosis.

PMID- 17001058
TI  - Advancing interdisciplinary health research: a synergism not to be denied.

PMID- 17001059
TI  - A meeting of minds: interdisciplinary research in the health sciences in Canada.
AB  - Brought together by the newly formed Canadian Academy of Health Sciences (CAHS),
      recognized national leaders in the 6 health sciences disciplines consider the
      environment for conducting interdisciplinary health research (IDHR) in Canada.
      Based on first-hand knowledge and thoughtful reflection, the authors argue that
      although much progress has been made in support of IDHR in Canada, the practical
      experience of researchers does not always bear this out. This article examines
      government, industry and academia to identify the cultural and structural
      characteristics that demand, promote or prevent IDHR in each sector. At its heart
      is the question, How can universities best support and enhance IDHR, not only for
      the benefit of science, but also to meet the growing needs of industry and
      government for intellectual capital? Focusing on the predominant health sciences
      disciplines, the authors define IDHR as a team of researchers, solidly grounded
      in their respective disciplines, who come together around an important and
      challenging health issue, the research question for which is determined by a
      shared understanding in an interactive and iterative process. In addition, they
      suggest that IDHR is directly linked to translational research, which is the
      application of basic science to clinical practice and the generation of
      scientific questions through clinical observation. This analysis of academic,
      industry and government sectors is not intended to offer rigorous data on the
      current state of IDHR in Canada. Rather, the goal is to stimulate research-policy
      dialogue by suggesting a number of immediate measures that can help promote IDHR
      in Canada. Recommended measures to support IDHR are aimed at better resourcing
      and recognition (by universities and granting agencies), along with novel
      approaches to training, such as government-and industry-based studentships. In
      addition, we recommend that professional organizations reconsider their policies
      on publication and governance. Although intended to maintain professional scopes
      of practice, these policies also serve to entrench disciplinary boundaries in
      research. We conclude by suggesting a number of research questions for a more
      rigorous assessment of the climate for IDHR in Canada. We call for an inventory
      and comparative analysis of academic centres, institutes and consortiums in
      Canada that strive to facilitate IDHR; an examination of the impact of
      professional organizations on health research, and on IDHR in particular; and a
      systematic review of research training opportunities that promote IDHR, with a
      view to identifying and replicating proven models.

PMID- 17001060
TI  - Health benefits of physical activity.

PMID- 17001061
TI  - An economical cure.

PMID- 17001062
TI  - REAP: an extended agenda for the clinical interview.

PMID- 17001063
TI  - Health benefits of physical activity.

PMID- 17001064
TI  - Health benefits of physical activity.

PMID- 17001065
TI  - Health benefits of physical activity.

PMID- 17001067
TI  - Statin and cancer risks: from tasseomancy of epidemiologic studies to meta
      analyses.

PMID- 17001068
TI  - Multicenter phase II study of bortezomib in patients with relapsed or refractory
      mantle cell lymphoma.
AB  - PURPOSE: Evaluate response rate, duration of response (DOR), time-to-progression
      (TTP), overall survival (OS), and safety of bortezomib treatment in patients with
      relapsed or refractory mantle cell lymphoma (MCL). PATIENTS AND METHODS:
      Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 of a 21-day
      cycle, for up to 17 cycles. Response and progression were determined using
      International Workshop Response Criteria, both using data from independent
      radiology review and by the investigators. Primary efficacy analyses were based
      on data from independent radiology review. RESULTS: In total, 155 patients were
      treated. Median number of prior therapies was one (range, one to three). Response
      rate in 141 assessable patients was 33% including 8% complete response
      (CR)/unconfirmed CR. Median DOR was 9.2 months. Median TTP was 6.2 months.
      Results by investigator assessments were similar. Median OS has not been reached
      after a median follow-up of 13.4 months. The safety profile of bortezomib was
      similar to previous experience in relapsed multiple myeloma. The most common
      adverse events grade 3 or higher were peripheral neuropathy (13%), fatigue (12%),
      and thrombocytopenia (11%). Death from causes that were considered to be
      treatment related was reported for 3% of patients. CONCLUSION: These results
      confirm the activity of bortezomib in relapsed or refractory MCL, with
      predictable and manageable toxicities. Bortezomib provides significant clinical
      activity in terms of durable and complete responses, and may therefore represent
      a new treatment option for this population with usually very poor outcome.
      Studies of bortezomib-based combinations in MCL are ongoing.

PMID- 17001069
TI  - Case-control comparison of at-home to total hospital care for autologous stem
      cell transplantation for hematologic malignancies.
AB  - PURPOSE: One of the most significant limitations of at-home autologous stem-cell
      transplantation (ASCT) is the necessity for hospital readmission. We developed an
      at-home ASCT program in which prophylactic ceftriaxone and treatment of febrile
      neutropenia with piperacillin and tazobactam was introduced to minimize the
      readmission rate. PATIENTS AND METHODS: Between November 2000 and February 2005,
      178 consecutive patients underwent ASCT for a hematologic malignancy. Of these,
      50 patients fulfilled the requirements for at-home ASCT. Results were compared
      with those observed in a control group of 50 patients individually matched to the
      group of patients treated at home for age, sex, diagnosis, stage of disease,
      conditioning, and source of stem cells. RESULTS: Febrile neutropenia occurred in
      fewer patients in the at-home group as compared with the hospitalized group (76%
      v 96%: P = .008), and duration of fever was also shorter in the at-home group
      (median, 2 and 6 days, respectively; range, 1 to 11 and 1 to 20 days,
      respectively; P = .00003). Hospital readmission in the at-home group was required
      in only four cases (8%). This resulted in a reduction of 18.6 days of
      hospitalization per patient. Likewise, total median charges were approximately
      half in the at-home group as compared with the in-hospital group (3,345 euro v
      6,250 euro, respectively; P < .00001). CONCLUSION: Results of at-home ASCT with
      prophylactic administration of ceftriaxone and domiciliary treatment of febrile
      neutropenia with piperacillin and tazobactam are highly satisfactory and
      significantly cheaper compared with those obtained with conventional in-hospital
      ASCT.

PMID- 17001070
TI  - Statins and cancer risk: a literature-based meta-analysis and meta-regression
      analysis of 35 randomized controlled trials.
AB  - PURPOSE: A growing body of literature suggests that statins may have
      chemopreventive potential against cancer. Our aim was to examine the strength of
      this association through a detailed meta-analysis and meta-regression analysis of
      randomized controlled trials (RCTs). METHODS: A comprehensive search for trials
      published up to 2005 was performed, reviews of each study were conducted, and
      data were abstracted. Before meta-analysis, the studies were evaluated for
      publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95%
      CIs were calculated using the random- and fixed-effects models. Subgroup,
      sensitivity, and meta-regression analyses were also conducted. RESULTS: Thirty
      five RCTs of statins for cardiovascular outcomes contributed to the analysis (n =
      109,143). The degree of variability between trials was consistent with what would
      be expected to occur by chance alone. Statin use was not associated with a
      substantially increased or decreased overall risk of cancer (RR = 0.99; 95% CI,
      0.94 to 1.04). Similarly, statin use did not significantly affect respiratory
      cancer risk (RR = 0.95; 95% CI, 0.83 to 1.09). However, the meta-regression
      analysis indicated that age of study participants modified the association
      between statin use and cancer risk (P = .003). CONCLUSION: Our findings do not
      support a protective effect of statins against cancer. However, this conclusion
      is limited by the relatively short follow-up periods (4.5 years on average) of
      the studies analyzed. Thus, it is important to continue monitoring the long-term
      safety profiles of statins. Until then, physicians need to be vigilant in
      ensuring that statin use remains restricted to the approved indications.

PMID- 17001071
TI  - Phase II trial evaluating the palliative benefit of second-line zoledronic acid
      in breast cancer patients with either a skeletal-related event or progressive
      bone metastases despite first-line bisphosphonate therapy.
AB  - PURPOSE: This study evaluated whether additional palliative benefits could be
      derived from the second-line use of the more potent bisphosphonate zoledronic
      acid in metastatic breast cancer patients with either progressive bone metastases
      or skeletal-related events (SRE), despite first-line therapy with either
      pamidronate or clodronate. PATIENTS AND METHODS: This prospective study evaluated
      the impact of second-line zoledronic acid on pain, quality of life, and markers
      of bone turnover (for example, urinary N-telopeptide [NTX]). Patients received
      monthly zoledronic acid (4 mg) for 3 months. Study evaluations were made weekly
      during the first month and again at week 8. No changes in chemotherapy or
      endocrine therapy were allowed in the month before or after commencing study
      treatment. RESULTS: Thirty-one women completed this study. By week 8, patients
      had experienced significant improvements in pain control (P < .001). There was a
      downward trend in urinary NTX levels over the same time period (P = .008).
      Overall, there was a trend towards a positive correlation between improvement in
      pain control and reduction in week one urinary NTX relative to baseline
      (Spearman's rho r = 0.27; P = .15). CONCLUSION: This is the first study to
      demonstrate that patients with either progressive bone metastases or SREs while
      on clodronate or pamidronate can have relevant palliative benefits with a switch
      to the more potent bisphosphonate zoledronic acid. This is reflected by
      significant improvements in pain control and bone turnover markers. If confirmed
      in randomized trials, these findings have major implications to the use of
      bisphosphonates in both the metastatic and adjuvant settings.

PMID- 17001072
TI  - RNA-binding motif protein 15 binds to the RNA transport element RTE and provides
      a direct link to the NXF1 export pathway.
AB  - Retroviruses/retroelements provide tools enabling the identification and
      dissection of basic steps for post-transcriptional regulation of cellular mRNAs.
      The RNA transport element (RTE) identified in mouse retrotransposons is
      functionally equivalent to constitutive transport element of Type D retroviruses,
      yet does not bind directly to the mRNA export receptor NXF1. Here, we report that
      the RNA-binding motif protein 15 (RBM15) recognizes RTE directly and specifically
      in vitro and stimulates export and expression of RTE-containing reporter mRNAs in
      vivo. Tethering of RBM15 to a reporter mRNA showed that RBM15 acts by promoting
      mRNA export from the nucleus. We also found that RBM15 binds to NXF1 and the two
      proteins cooperate in stimulating RTE-mediated mRNA export and expression. Thus,
      RBM15 is a novel mRNA export factor and is part of the NXF1 pathway. We propose
      that RTE evolved as a high affinity RBM15 ligand to provide a splicing
      independent link to NXF1, thereby ensuring efficient nuclear export and
      expression of retrotransposon transcripts.

PMID- 17001073
TI  - The 19-amino acid cassette of cyclooxygenase-2 mediates entry of the protein into
      the endoplasmic reticulum-associated degradation system.
AB  - Cyclooxygenase (COX) isoforms catalyze the committed step in prostaglandin
      biosynthesis. The primary structures of COX-1 and COX-2 are very similar except
      that COX-2 has a 19-amino acid (19-AA) segment of unknown function located just
      inside its C terminus. Here we provide evidence that the major role of the 19-AA
      cassette is to mediate entry of COX-2 into the ER-associated degradation system
      that transports ER proteins to the cytoplasm. COX-1 is constitutively expressed
      in many cells, whereas COX-2 is usually expressed inducibly and transiently. In
      murine NIH/3T3 fibroblasts, we find that COX-2 protein is degraded with a half
      life (t(1/2)) of about 2 h, whereas COX-1 is reasonably stable (t(1/2) > 12 h);
      COX-2 degradation is retarded by 26 S proteasome inhibitors. Similarly, COX-1
      expressed heterologously in HEK293 cells is quite stable (t(1/2) > 24 h), whereas
      COX-2 expressed heterologously is degraded with a t(1/2) of approximately 5 h,
      and its degradation is slowed by proteasome inhibitors. A deletion mutant of COX
      2 was prepared lacking 18 residues of the 19-AA cassette. This mutant retains
      native COX-2 activity but, unlike native COX-2, is stable in HEK293 cells.
      Conversely, inserting the COX-2 19-AA cassette near the C terminus of COX-1
      yields a mutant ins594-612 COX-1 that is unstable (t(1/2) approximately 3 h).
      Mutation of Asn-594, an N-glycosylation site at the beginning of the 19-AA
      cassette, stabilizes both COX-2 and ins594-612 COX-1; nonetheless, COX mutants
      that are glycosylated at Asn-594 but lack the remainder of the 19-amino acid
      cassette (i.e. del597-612 COX-2 and ins594-596 COX-1) are stable. Thus, although
      glycosylation of Asn-594 is necessary for COX-2 degradation, at least part of the
      remainder of the 19-AA insert is also required. Finally, kifunensine, a
      mannosidase inhibitor that can block entry of ER proteins into the ER-associated
      degradation system, retards COX-2 degradation.

PMID- 17001074
TI  - Mass spectrometric analysis of glycine receptor-associated gephyrin splice
      variants.
AB  - Gephyrin is an ubiquitously expressed protein that, in the nervous system, is
      essential for synaptic anchoring of glycine receptors (GlyRs) and major GABAA
      receptor subtypes. The binding of gephyrin to the GlyR depends on an amphipathic
      motif within the large intracellular loop of the GlyRbeta subunit. The mouse
      gephyrin gene consists of 30 exons. Ten of these exons, encoding cassettes of 5
      40 amino acids, are subject to alternative splicing (C1-C7, C4'-C6'). Since one
      of the cassettes, C5', has recently been reported to exclude GlyRs from GABAergic
      synapses, we investigated which cassettes are found in gephyrin associated with
      the GlyR. Gephyrin variants were purified from rat spinal cord, brain, and liver
      by binding to the glutathione S-transferase-tagged GlyRbeta loop or copurified
      with native GlyR from spinal cord by affinity chromatography and analyzed by mass
      spectrometry. In addition to C2 and C6', already known to be prominent, C4 was
      found to be abundant in gephyrin from all tissues examined. The nonneuronal
      cassette C3 was easily detected in liver but not in GlyR-associated gephyrin from
      spinal cord. C5 was present in brain and spinal cord polypeptides, whereas C5'
      was coisolated mainly from liver. Notably C5'-containing gephyrin bound to the
      GlyRbeta loop, inconsistent with its proposed selectivity for GABAA receptors.
      Our data show that GlyR-associated gephyrin, lacking C3, but enriched in C4
      without C5, differs from other neuronal and nonneuronal gephyrin isoforms.

PMID- 17001075
TI  - Structural characterization of Spo0E-like protein-aspartic acid phosphatases that
      regulate sporulation in bacilli.
AB  - Spore formation is an extreme response of many bacterial species to starvation.
      In the case of pathogenic species of Bacillus and Clostridium, it is also a
      component of disease transmission. Entry into the pathway of sporulation in
      Bacillus subtilis and its relatives is controlled by an expanded two-component
      system in which starvation signals lead to the activation of sensor kinases and
      phosphorylation of the master sporulation response regulator Spo0A. Accumulation
      of threshold concentrations of Spo0A approximately P heralds the commitment to
      sporulation. Countering the activities of the sensor kinases are phosphatases
      such as Spo0E, which dephosphorylate Spo0A approximately P and inhibit
      sporulation. Spo0E-like protein-aspartic acid-phosphate phosphatases, consisting
      of 50-90 residues, are conserved in sporeforming bacteria and unrelated in
      sequence to proteins of known structure. Here we determined the structures of the
      Spo0A approximately P phosphatases BA1655 and BA5174 from Bacillus anthracis
      using nuclear magnetic resonance spectroscopy. Each is composed of two anti
      parallel alpha-helices flanked by flexible regions at the termini. The signature
      SQELD motif (SRDLD in BA1655) is situated in the middle of helix alpha2 with its
      polar residues projecting outward. BA5174 is a monomer, whereas BA1655 is a
      dimer. The four-helix bundle structure in the dimer is reminiscent of the
      phosphotransferase Spo0B and the chemotaxis phosphatase CheZ, although in
      contrast to these systems, the subunits in BA1655 are in head-to-tail rather than
      head-to-head apposition. The implications of the structures for interactions
      between the phosphatases and their substrate Spo0A approximately P are discussed.

PMID- 17001076
TI  - Interaction of the membrane-bound GlnK-AmtB complex with the master regulator of
      nitrogen metabolism TnrA in Bacillus subtilis.
AB  - PII proteins are widespread and highly conserved signal transduction proteins
      occurring in bacteria, Archaea, and plants and play pivotal roles in controlling
      nitrogen assimilatory metabolism. This study reports on biochemical properties of
      the PII-homologue GlnK (originally termed NrgB) in Bacillus subtilis (BsGlnK).
      Like other PII proteins, the native BsGlnK protein has a trimeric structure and
      readily binds ATP in the absence of divalent cations, whereas 2-oxoglutarate is
      only weakly bound. In contrast to other PII-like proteins, Mg2+ severely affects
      its ATP-binding properties. BsGlnK forms a tight complex with the membrane-bound
      ammonium transporter AmtB (NrgA), from which it can be relieved by millimolar
      concentrations of ATP. Immunoprecipitation and co-localization experiments
      identified a novel interaction between the BsGlnK-AmtB complex and the major
      transcription factor of nitrogen metabolism, TnrA. In vitro in the absence of
      ATP, TnrA is completely tethered to membrane (AmtB)-bound GlnK, whereas in
      extracts from BsGlnK- or AmtB-deficient cells, TnrA is entirely soluble. The
      presence of 4 mm ATP leads to concomitant solubilization of BsGlnK and TnrA. This
      ATP-dependent membrane re-localization of TnrA by BsGlnK/AmtB may present a novel
      mechanism to control the global nitrogen-responsive transcription regulator TnrA
      in B. subtilis under certain physiological conditions.

PMID- 17001077
TI  - slc26a3 (dra)-deficient mice display chloride-losing diarrhea, enhanced colonic
      proliferation, and distinct up-regulation of ion transporters in the colon.
AB  - Mutations in the SLC26A3 (DRA (down-regulated in adenoma)) gene constitute the
      molecular etiology of congenital chloride-losing diarrhea in humans. To ascertain
      its role in intestinal physiology, gene targeting was used to prepare mice
      lacking slc26a3. slc26a3-deficient animals displayed postpartum lethality at low
      penetrance. Surviving dra-deficient mice exhibited high chloride content
      diarrhea, volume depletion, and growth retardation. In addition, the large
      intestinal loops were distended, with colonic mucosa exhibiting an aberrant
      growth pattern and the colonic crypt proliferative zone being greatly expanded in
      slc26a3-null mice. Apical membrane chloride/base exchange activity was sharply
      reduced, and luminal content was more acidic in slc26a3-null mouse colon. The
      epithelial cells in the colon displayed unique adaptive regulation of ion
      transporters; NHE3 expression was enhanced in the proximal and distal colon,
      whereas colonic H,K-ATPase and the epithelial sodium channel showed massive up
      regulation in the distal colon. Plasma aldosterone was increased in slc26a3-null
      mice. We conclude that slc26a3 is the major apical chloride/base exchanger and is
      essential for the absorption of chloride in the colon. In addition, slc26a3
      regulates colonic crypt proliferation. Deletion of slc26a3 results in chloride
      rich diarrhea and is associated with compensatory adaptive up-regulation of ion
      absorbing transporters.

PMID- 17001078
TI  - Surface charge interactions of the FMN module govern catalysis by nitric-oxide
      synthase.
AB  - The FMN module of nitric-oxide synthase (NOS) plays a pivotal role by
      transferring NADPH-derived electrons to the enzyme heme for use in oxygen
      activation. The process may involve a swinging mechanism in which the same face
      of the FMN module accepts and provides electrons during catalysis. Crystal
      structure shows that this face of the FMN module is electronegative, whereas the
      complementary interacting surface is electropositive, implying that charge
      interactions enable function. We used site-directed mutagenesis to investigate
      the roles of six electronegative surface residues of the FMN module in electron
      transfer and catalysis in neuronal NOS. Results are interpreted in light of
      crystal structures of NOS and related flavoproteins. Neutralizing or reversing
      the negative charge of each residue altered the NO synthesis, NADPH oxidase, and
      cytochrome c reductase activities of neuronal NOS and also altered heme
      reduction. The largest effects occurred at the NOS-specific charged residue
      Glu(762). Together, the results suggest that electrostatic interactions of the
      FMN module help to regulate electron transfer and to minimize flavin autoxidation
      and the generation of reactive oxygen species during NOS catalysis.

PMID- 17001079
TI  - P2X5 subunit assembly requires scaffolding by the second transmembrane domain and
      a conserved aspartate.
AB  - Functional homomeric and heteromeric ATP-gated P2X receptor channels have been
      shown to display a characteristic trimeric architecture. Of the seven different
      isoforms (designated P2X(1)-P2X(7)), P2X(5) occurs in humans primarily as a non
      functional variant lacking the C-terminal end of the ectodomain and the outer
      half of the second transmembrane domain. We show that this truncated variant,
      which results from the splice-skipping of exon 10, is prone to subunit
      aggregation because the residual transmembrane domain 2 is too short to insert
      into the membrane. Alleviation of the negative hydrophobic mismatch by the
      addition of a stretch of moderately hydrophobic residues enabled formation of a
      second membrane-spanning domain and strictly parallel homotrimerization.
      Systematic mutagenesis identified only one transmembrane domain 2 residue,
      Asp(355), which supported homotrimerization in a side chain-specific manner. Our
      results indicate that transmembrane domain 2 formation contributes 2-fold to
      hP2X(5) homotrimerization by tethering the end of the ectodomain to the membrane,
      thereby topologically restricting conformational mobility, and by intramembrane
      positioning of Asp(355). While transmembrane domain 2 appears to favor assembly
      by enabling productive subunit interactions in the ectodomain, Asp(355) seems to
      assist by simultaneously driving intramembrane helix interactions. Overall, these
      results indicate a complex interplay between topology, helix-helix interactions,
      and oligomerization to achieve a correctly folded structure.

PMID- 17001080
TI  - The location of asparagine-linked glycans on West Nile virions controls their
      interactions with CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin).
AB  - Mammalian cell-derived West Nile virus preferentially infects cells expressing
      the C-type lectin CD209L (dendritic cellspecific ICAM-3 grabbing nonintegrin
      related protein; liver- and lymph node-specific ICAM-3 grabbing nonintegrin) but
      not cells expressing CD209 (dendritic cell-specific ICAM-3 grabbing nonintegrin).
      In contrast, Dengue virus infection is enhanced in cells expressing either
      attachment factor. The West Nile virus envelope (E) protein contains a single N
      linked glycosylation site at residue 154, whereas Dengue virus E contains sites
      at residues 153 and 67. We introduced a glycosylation site at position 67 into
      West Nile virus E. Reporter virus particles pseudotyped with this E protein
      infected cells using either CD209 or CD209L. We also introduced glycosylation
      sites at several novel positions. All sites allowed CD209L-mediated infection,
      but only a subset promoted CD209 use. As seen for other viruses, mannose-rich
      glycans on West Nile virus were required for its interactions with CD209.
      Surprisingly, however, mannose-rich glycans were not required for CD209L-mediated
      infection. Complex glycans, particularly N-acetylglucosamine-terminated
      structures, were able to mediate reporter virus particle interactions with
      CD209L. We propose that CD209L recognizes glycosylated flaviviruses with broad
      specificity, whereas CD209 is selective for flaviviruses bearing mannose-rich
      glycans. The location of the N-linked glycosylation sites on a virion determines
      the types of glycans incorporated, thus controlling viral tropism for CD209
      expressing cells.

PMID- 17001081
TI  - Identification of an hexapeptide that binds to a surface pocket in cyclin A and
      inhibits the catalytic activity of the complex cyclin-dependent kinase 2-cyclin
      A.
AB  - The protein-protein complexes formed between different cyclins and cyclin
      dependent kinases (CDKs) are central to cell cycle regulation. These complexes
      represent interesting points of chemical intervention for the development of
      antineoplastic molecules. Here we describe the identification of an all d-amino
      acid hexapeptide, termed NBI1, that inhibits the kinase activity of the cyclin
      dependent kinase 2 (cdk2)-cyclin A complex through selective binding to cyclin A.
      The mechanism of inhibition is non-competitive for ATP and non-competitive for
      protein substrates. In contrast to the existing CDKs peptide inhibitors, the
      hexapeptide NBI1 interferes with the formation of the cdk2-cyclin A complex.
      Furthermore, a cell-permeable derivative of NBI1 induces apoptosis and inhibits
      proliferation of tumor cell lines. Thus, the NBI1-binding site on cyclin A may
      represent a new target site for the selective inhibition of activity cdk2-cyclin
      A complex.

PMID- 17001082
TI  - The Rab4A effector protein Rabip4 is involved in migration of NIH 3T3
      fibroblasts.
AB  - The small GTP-binding protein Rab4 has been involved in the recycling of
      alphavbeta3 integrins in response to platelet-derived growth factor (PDGF)
      stimulation suggesting a role for Rab4 in cell adhesion and migration. In this
      study, we explored the role of Rabip4 and Rabip4', two Rab4 effector proteins, in
      migration of NIH 3T3 fibroblasts. In these cells, Rabip4 and Rabip4',
      collectively named Rabip4s, were partially co-localized with the early endosomal
      marker EEA1. PDGF treatment re-distributed endogenous Rabip4s toward the cell
      periphery where they colocalized with F-actin. In cells expressing green
      fluorescent protein (GFP)-Rabip4 or GFP-Rabip4', constitutive appearance of GFP
      Rabip4s at the cell periphery was accompanied by local increase in cortical F
      actin in membrane ruffles at the leading edge. The expression of GFP-Rabip4
      induced an increased migration compared with control cells expressing GFP alone,
      even in the absence of PDGF stimulation. On the contrary, in cells expressing a
      mutated form of Rabip4s unable to interact with Rab4, lack of typical leading
      edge was observed. Furthermore, PDGF treatment did not stimulate the migration of
      these cells. Furthermore, down-regulation of the expression of Rabip4s inhibited
      PDGF-stimulated cell migration. Endogenous Rabip4s were localized with alphav
      integrins at the leading edge following PDGF treatment, whereas in cells
      expressing GFP-Rabip4s, alphav integrins, together with GFP-Rabip4s, were
      constitutively localized at the leading edge. In contrast, reduction in Rabip4s
      expression levels using small interfering RNA was associated with impaired PDGF
      induced translocation of alphav integrins toward the leading edge. Taken
      together, our data provide evidence that Rabip4s, possibly via their interaction
      with Rab4, regulate integrin trafficking and are involved in the migration of NIH
      3T3 fibroblasts.

PMID- 17001083
TI  - The mitochondrial citrate/isocitrate carrier plays a regulatory role in glucose
      stimulated insulin secretion.
AB  - Glucose-stimulated insulin secretion (GSIS) is mediated in part by glucose
      metabolism-driven increases in ATP/ADP ratio, but by-products of mitochondrial
      glucose metabolism also play an important role. Here we investigate the role of
      the mitochondrial citrate/isocitrate carrier (CIC) in regulation of GSIS.
      Inhibition of CIC activity in INS-1-derived 832/13 cells or primary rat islets by
      the substrate analogue 1,2,3-benzenetricarboxylate (BTC) resulted in potent
      inhibition of GSIS, involving both first and second phase secretion. A
      recombinant adenovirus containing a CIC-specific siRNA (Ad-siCIC) dose
      dependently reduced CIC expression in 832/13 cells and caused parallel inhibitory
      effects on citrate accumulation in the cytosol. Ad-siCIC treatment did not affect
      glucose utilization, glucose oxidation, or ATP/ADP ratio but did inhibit glucose
      incorporation into fatty acids and glucose-induced increases in NADPH/NADP+ ratio
      relative to cells treated with a control siRNA virus (Ad-siControl). Ad-siCIC
      also inhibited GSIS in 832/13 cells, whereas overexpression of CIC enhanced GSIS
      and raised cytosolic citrate levels. In normal rat islets, Ad-siCIC treatment
      also suppressed CIC mRNA levels and inhibited GSIS. We conclude that export of
      citrate and/or isocitrate from the mitochondria to the cytosol is an important
      step in control of GSIS.

PMID- 17001084
TI  - A tail of multiple calcium-sensing domains.

PMID- 17001085
TI  - Intra- and intersubunit cooperativity in activation of BK channels by Ca2+.
AB  - The activation of BK channels by Ca(2+) is highly cooperative, with small changes
      in intracellular Ca(2+) concentration having large effects on open probability
      (Po). Here we examine the mechanism of cooperative activation of BK channels by
      Ca(2+). Each of the four subunits of BK channels has a large intracellular COOH
      terminus with two different high-affinity Ca(2+) sensors: an RCK1 sensor
      (D362/D367) located on the RCK1 (regulator of conductance of K(+)) domain and a
      Ca-bowl sensor located on or after the RCK2 domain. To determine interactions
      among these Ca(2+) sensors, we examine channels with eight different
      configurations of functional high-affinity Ca(2+) sensors on the four subunits.
      We find that the RCK1 sensor and Ca bowl contribute about equally to Ca(2+)
      activation of the channel when there is only one high-affinity Ca(2+) sensor per
      subunit. We also find that an RCK1 sensor and a Ca bowl on the same subunit are
      much more effective in increasing Po than when they are on different subunits,
      indicating positive intrasubunit cooperativity. If it is assumed that BK channels
      have a gating ring similar to MthK channels with alternating RCK1 and RCK2
      domains and that the Ca(2+) sensors act at the flexible (rather than fixed)
      interfaces between RCK domains, then a comparison of the distribution of Ca(2+)
      sensors with the observed responses suggest that the interface between RCK1 and
      RCK2 domains on the same subunit is flexible. On this basis, intrasubunit
      cooperativity arises because two high-affinity Ca(2+) sensors acting across a
      flexible interface are more effective in opening the channel than when acting at
      separate interfaces. An allosteric model incorporating intrasubunit cooperativity
      nested within intersubunit cooperativity could approximate the Po vs. Ca(2+)
      response for eight possible subunit configurations of the high-affinity Ca(2+)
      sensors as well as for three additional configurations from a previous study.

PMID- 17001086
TI  - Contributions of stretch activation to length-dependent contraction in murine
      myocardium.
AB  - The steep relationship between systolic force production and end diastolic volume
      (Frank-Starling relationship) in myocardium is a potentially important mechanism
      by which the work capacity of the heart varies on a beat-to-beat basis, but the
      molecular basis for the effects of myocardial fiber length on cardiac work are
      still not well understood. Recent studies have suggested that an intrinsic
      property of myocardium, stretch activation, contributes to force generation
      during systolic ejection in myocardium. To examine the role of stretch activation
      in length dependence of activation we recorded the force responses of murine
      skinned myocardium to sudden stretches of 1% of muscle length at both short (1.90
      microm) and long (2.25 microm) sarcomere lengths (SL). Maximal Ca(2+)-activated
      force and Ca(2+) sensitivity of force were greater at longer SL, such that more
      force was produced at a given Ca(2+) concentration. Sudden stretch of myocardium
      during an otherwise isometric contraction resulted in a concomitant increase in
      force that quickly decayed to a minimum and was followed by a delayed development
      of force, i.e., stretch activation, to levels greater than prestretch force. At
      both maximal and submaximal activations, increased SL significantly reduced the
      initial rate of force decay following stretch; at submaximal activations (but not
      at maximal) the rate of delayed force development was accelerated. This
      combination of mechanical effects of increased SL would be expected to increase
      force generation during systolic ejection in vivo and prolong the period of
      ejection. These results suggest that sarcomere length dependence of stretch
      activation contributes to the steepness of the Frank-Starling relationship in
      living myocardium.

PMID- 17001088
TI  - Implementation of semi-automated cloning and prokaryotic expression screening:
      the impact of SPINE.
AB  - The implementation of high-throughput (HTP) cloning and expression screening in
      Escherichia coli by 14 laboratories in the Structural Proteomics In Europe
      (SPINE) consortium is described. Cloning efficiencies of greater than 80% have
      been achieved for the three non-ligation-based cloning techniques used, namely
      Gateway, ligation-indendent cloning of PCR products (LIC-PCR) and In-Fusion, with
      LIC-PCR emerging as the most cost-effective. On average, two constructs have been
      made for each of the approximately 1700 protein targets selected by SPINE for
      protein production. Overall, HTP expression screening in E. coli has yielded 32%
      soluble constructs, with at least one for 70% of the targets. In addition to the
      implementation of HTP cloning and expression screening, the development of two
      novel technologies is described, namely library-based screening for soluble
      constructs and parallel small-scale high-density fermentation.

PMID- 17001087
TI  - Cyclic nucleotide-gated ion channels in rod photoreceptors are protected from
      retinoid inhibition.
AB  - In vertebrate rods, photoisomerization of the 11-cis retinal chromophore of
      rhodopsin to the all-trans conformation initiates a biochemical cascade that
      closes cGMP-gated channels and hyperpolarizes the cell. All-trans retinal is
      reduced to retinol and then removed to the pigment epithelium. The pigment
      epithelium supplies fresh 11-cis retinal to regenerate rhodopsin. The recent
      discovery that tens of nanomolar retinal inhibits cloned cGMP-gated channels at
      low [cGMP] raised the question of whether retinoid traffic across the plasma
      membrane of the rod might participate in the signaling of light. Native channels
      in excised patches from rods were very sensitive to retinoid inhibition.
      Perfusion of intact rods with exogenous 9- or 11-cis retinal closed cGMP-gated
      channels but required higher than expected concentrations. Channels reopened
      after perfusing the rod with cellular retinoid binding protein II. PDE activity,
      flash response kinetics, and relative sensitivity were unchanged, ruling out
      pharmacological activation of the phototransduction cascade. Bleaching of
      rhodopsin to create all-trans retinal and retinol inside the rod did not produce
      any measurable channel inhibition. Exposure of a bleached rod to 9- or 11-cis
      retinal did not elicit channel inhibition during the period of rhodopsin
      regeneration. Microspectrophotometric measurements showed that exogenous 9- or 11
      cis retinal rapidly cross the plasma membrane of bleached rods and regenerate
      their rhodopsin. Although dark-adapted rods could also take up large quantities
      of 9-cis retinal, which they converted to retinol, the time course was slow.
      Apparently cGMP-gated channels in intact rods are protected from the inhibitory
      effects of retinoids that cross the plasma membrane by a large-capacity buffer.
      Opsin, with its chromophore binding pocket occupied (rhodopsin) or vacant, may be
      an important component. Exceptionally high retinoid levels, e.g., associated with
      some retinal degenerations, could overcome the buffer, however, and impair
      sensitivity or delay the recovery after exposure to bright light.

PMID- 17001089
TI  - Eukaryotic expression: developments for structural proteomics.
AB  - The production of sufficient quantities of protein is an essential prelude to a
      structure determination, but for many viral and human proteins this cannot be
      achieved using prokaryotic expression systems. Groups in the Structural
      Proteomics In Europe (SPINE) consortium have developed and implemented high
      throughput (HTP) methodologies for cloning, expression screening and protein
      production in eukaryotic systems. Studies focused on three systems: yeast (Pichia
      pastoris and Saccharomyces cerevisiae), baculovirus-infected insect cells and
      transient expression in mammalian cells. Suitable vectors for HTP cloning are
      described and results from their use in expression screening and protein
      production pipelines are reported. Strategies for co-expression, selenomethionine
      labelling (in all three eukaryotic systems) and control of glycosylation (for
      secreted proteins in mammalian cells) are assessed.

PMID- 17001090
TI  - The impact of protein characterization in structural proteomics.
AB  - Protein characterization plays a role in two key aspects of structural
      proteomics. The first is the quality assessment of the produced protein
      preparations. Obtaining well diffracting crystals is one of the major bottlenecks
      in the structure-determination pipeline. Often, this is caused by the poor
      quality of the protein preparation used for crystallization trials. Hence, it is
      essential to perform an extensive quality assessment of the protein preparations
      prior to crystallization and to use the results in the evaluation of the process.
      Here, a protein-production and crystallization strategy is proposed with
      threshold values for protein purity (95%) and monodispersity (85%) below which a
      further optimization of the protein-production process is strongly recommended.
      The second aspect is the determination of protein characteristics such as
      domains, oligomeric state, post-translational modifications and protein-protein
      and protein-ligand interactions. In this paper, applications and new developments
      of protein-characterization methods using MS, fluorescence spectroscopy, static
      light scattering, analytical ultracentrifugation and small-angle X-ray scattering
      within the EC Structural Proteomics in Europe contract are described. Examples of
      the application of the various methods are given.

PMID- 17001091
TI  - SPINE high-throughput crystallization, crystal imaging and recognition
      techniques: current state, performance analysis, new technologies and future
      aspects.
AB  - This paper reviews the developments in high-throughput and nanolitre-scale
      protein crystallography technologies within the remit of workpackage 4 of the
      Structural Proteomics In Europe (SPINE) project since the project's inception in
      October 2002. By surveying the uptake, use and experience of new technologies by
      SPINE partners across Europe, a picture emerges of highly successful adoption of
      novel working methods revolutionizing this area of structural biology. Finally, a
      forward view is taken of how crystallization methodologies may develop in the
      future.

PMID- 17001092
TI  - NMR in the SPINE Structural Proteomics project.
AB  - This paper describes the developments, role and contributions of the NMR
      spectroscopy groups in the Structural Proteomics In Europe (SPINE) consortium.
      Focusing on the development of high-throughput (HTP) pipelines for NMR structure
      determinations of proteins, all aspects from sample preparation, data
      acquisition, data processing, data analysis to structure determination have been
      improved with respect to sensitivity, automation, speed, robustness and
      validation. Specific highlights are protonless (13)C-direct detection methods and
      inferential structure determinations (ISD). In addition to technological
      improvements, these methods have been applied to deliver over 60 NMR structures
      of proteins, among which are five that failed to crystallize. The inclusion of
      NMR spectroscopy in structural proteomics pipelines improves the success rate for
      protein structure determinations.

PMID- 17001093
TI  - High-throughput sample handling and data collection at synchrotrons: embedding
      the ESRF into the high-throughput gene-to-structure pipeline.
AB  - An automatic data-collection system has been implemented and installed on seven
      insertion-device beamlines and a bending-magnet beamline at the ESRF (European
      Synchrotron Radiation Facility) as part of the SPINE (Structural Proteomics In
      Europe) development of an automated structure-determination pipeline. The system
      allows remote interaction with beamline-control systems and automatic sample
      mounting, alignment, characterization, data collection and processing. Reports of
      all actions taken are available for inspection via database modules and web
      services.

PMID- 17001094
TI  - SPINE workshop on automated X-ray analysis: a progress report.
AB  - The Structural Proteomics In Europe (SPINE) consortium contained a workpackage to
      address the automated X-ray analysis of macromolecules. The aim of this
      workpackage was to increase the throughput of three-dimensional structures while
      maintaining the high quality of conventional analyses. SPINE was able to bring
      together developers of software with users from the partner laboratories. Here,
      the results of a workshop organized by the consortium to evaluate software
      developed in the member laboratories against a set of bacterial targets are
      described. The major emphasis was on molecular-replacement suites, where
      automation was most advanced. Data processing and analysis, use of experimental
      phases and model construction were also addressed, albeit at a lower level.

PMID- 17001095
TI  - SPINE bioinformatics and data-management aspects of high-throughput structural
      biology.
AB  - SPINE (Structural Proteomics In Europe) was established in 2002 as an integrated
      research project to develop new methods and technologies for high-throughput
      structural biology. Development areas were broken down into workpackages and this
      article gives an overview of ongoing activity in the bioinformatics workpackage.
      Developments cover target selection, target registration, wet and dry laboratory
      data management and structure annotation as they pertain to high-throughput
      studies. Some individual projects and developments are discussed in detail, while
      those that are covered elsewhere in this issue are treated more briefly. In
      particular, this overview focuses on the infrastructure of the software that
      allows the experimentalist to move projects through different areas that are
      crucial to high-throughput studies, leading to the collation of large data sets
      which are managed and eventually archived and/or deposited.

PMID- 17001097
TI  - First steps towards effective methods in exploiting high-throughput technologies
      for the determination of human protein structures of high biomedical value.
AB  - The EC 'Structural Proteomics In Europe' contract is aimed specifically at the
      atomic resolution structure determination of human protein targets closely linked
      to health, with a focus on cancer (kinesins, kinases, proteins from the ubiquitin
      pathway), neurological development and neurodegenerative diseases and immune
      recognition. Despite the challenging nature of the analysis of such targets,
      approximately 170 structures have been determined to date. Here, the impact of
      high-throughput technologies, such as parallel expression of multiple constructs,
      the use of standardized refolding protocols and optimized crystallization screens
      or the use of mass spectrometry to assist sample preparation, on the structural
      biology of mammalian protein targets is illustrated through selected examples.

PMID- 17001096
TI  - Application of the use of high-throughput technologies to the determination of
      protein structures of bacterial and viral pathogens.
AB  - The Structural Proteomics In Europe (SPINE) programme is aimed at the development
      and implementation of high-throughput technologies for the efficient structure
      determination of proteins of biomedical importance, such as those of bacterial
      and viral pathogens linked to human health. Despite the challenging nature of
      some of these targets, 175 novel pathogen protein structures (approximately 220
      including complexes) have been determined to date. Here the impact of several
      technologies on the structural determination of proteins from human pathogens is
      illustrated with selected examples, including the parallel expression of multiple
      constructs, the use of standardized refolding protocols and optimized
      crystallization screens.

PMID- 17001098
TI  - Recombinant protein expression and solubility screening in Escherichia coli: a
      comparative study.
AB  - Producing soluble proteins in Escherichia coli is still a major bottleneck for
      structural proteomics. Therefore, screening for soluble expression on a small
      scale is an attractive way of identifying constructs that are likely to be
      amenable to structural analysis. A variety of expression-screening methods have
      been developed within the Structural Proteomics In Europe (SPINE) consortium and
      to assist the further refinement of such approaches, eight laboratories
      participating in the network have benchmarked their protocols. For this study,
      the solubility profiles of a common set of 96 His(6)-tagged proteins were
      assessed by expression screening in E. coli. The level of soluble expression for
      each target was scored according to estimated protein yield. By reference to a
      subset of the proteins, it is demonstrated that the small-scale result can
      provide a useful indicator of the amount of soluble protein likely to be produced
      on a large scale (i.e. sufficient for structural studies). In general, there was
      agreement between the different groups as to which targets were not soluble and
      which were the most soluble. However, for a large number of the targets there
      were wide discrepancies in the results reported from the different screening
      methods, which is correlated with variations in the procedures and the range of
      parameters explored. Given finite resources, it appears that the question of how
      to most effectively explore ;expression space' is similar to several other multi
      parameter problems faced by crystallographers, such as crystallization.

PMID- 17001099
TI  - GRETA, a new multifermenter system for structural genomics and process
      optimization.
AB  - As part of the Structural Proteomics In Europe (SPINE) project, the automated
      multifermenter system GRETA has been developed with structural genomics as a
      major application. GRETA comprises 6-24 parallel fermentation chambers, each with
      individual control of fermentation parameters such as temperature, stirring, pH,
      dissolved oxygen concentration and feed profiles. Six human proteins were used to
      optimize the GRETA fermentation processes and to compare these processes with
      typical baffled-flask protocols used in structural genomics projects. The
      optimized GRETA processes allows several times more protein to be produced per
      litre of culture with limited manual intervention and constitutes a potentially
      useful alternative both for scale-up production in structural proteomic projects
      and for fermentation-process optimization.

PMID- 17001100
TI  - Co-expression of protein complexes in prokaryotic and eukaryotic hosts:
      experimental procedures, database tracking and case studies.
AB  - Structure determination and functional characterization of macromolecular
      complexes requires the purification of the different subunits in large quantities
      and their assembly into a functional entity. Although isolation and structure
      determination of endogenous complexes has been reported, much progress has to be
      made to make this technology easily accessible. Co-expression of subunits within
      hosts such as Escherichia coli and insect cells has become more and more
      amenable, even at the level of high-throughput projects. As part of SPINE
      (Structural Proteomics In Europe), several laboratories have investigated the use
      co-expression techniques for their projects, trying to extend from the common
      binary expression to the more complicated multi-expression systems. A new system
      for multi-expression in E. coli and a database system dedicated to handle co
      expression data are described. Results are also reported from various case
      studies investigating different methods for performing co-expression in E. coli
      and insect cells.

PMID- 17001101
TI  - A time- and cost-efficient system for high-level protein production in mammalian
      cells.
AB  - Most proteins for structural biology studies are produced by high-level
      expression in Escherichia coli. However, prokaryotic based expression systems
      fail to generate correctly folded functional forms of many proteins and hence a
      variety of eukaryotic based expression systems have been developed. Of these,
      yeast and baculovirus-infected insect cells currently represent the expression
      systems of choice for structural biologists. Here, protocols for a simple, fast
      and affordable method for transient protein expression in mammalian cells are
      reported. The results demonstrate that it combines several features necessary for
      the production of suitable samples for structural biology, in particular protein
      crystallography, namely high protein yield, straightforward purification,
      selenomethionine incorporation and control of N-linked glycosylation. The system
      is suitable for use in conventional laboratories or can be implemented in a
      medium- or high-throughput pipeline.

PMID- 17001102
TI  - Automation of sample mounting for macromolecular crystallography.
AB  - A standard sample holder and vial for cryocooled macromolecular crystals has been
      defined for use with robotic sample changers. This SPINE standard sample holder
      is a modified version, with added features and specifications, of sample holders
      in common use. In particular, the SPINE standard meets the precision required for
      automatic sample exchange and includes a cap that is identified by a two
      dimensional datamatrix code as well as an optional vial. At the ESRF, the sample
      holder standard is in use with the EMBL/ESRF/BM14 robotic sample changer (SC3)
      which is installed on eight beamlines. The SC3 can hold up to 50 crystals stored
      in five baskets. A datamatrix reader in the SC3 ensures safe management of the
      sample flow and facilitates fully automatic screening and characterization of
      samples. Tools for handling and transporting 50 samples in a dry shipping dewar
      have been developed. In addition to the SC3, the SPINE sample holder is currently
      compatible with a number of other robotic sample changers.

PMID- 17001103
TI  - Honing the in silico toolkit for detecting protein disorder.
AB  - Not all proteins form well defined three-dimensional structures in their native
      states. Some amino-acid sequences appear to strongly favour the disordered state,
      whereas some can apparently transition between disordered and ordered states
      under the influence of changes in the biological environment, thereby playing an
      important role in processes such as signalling. Although important biologically,
      for the structural biologist disordered regions of proteins can be disastrous
      even preventing successful structure determination. The accurate prediction of
      disorder is therefore important, not least for directing the design of expression
      constructs so as to maximize the chances of successful structure determination.
      Such design criteria have become integral to the construct-design strategies of
      laboratories within the Structural Proteomics In Europe (SPINE) consortium. This
      paper assesses the current state of the art in disorder prediction in terms of
      prediction reliability and considers how best to use these methods to guide
      construct design. Finally, it presents a brief discussion as to how methods of
      prediction might be improved in the future.

PMID- 17001104
TI  - Application of high-throughput technologies to a structural proteomics-type
      analysis of Bacillus anthracis.
AB  - A collaborative project between two Structural Proteomics In Europe (SPINE)
      partner laboratories, York and Oxford, aimed at high-throughput (HTP) structure
      determination of proteins from Bacillus anthracis, the aetiological agent of
      anthrax and a biomedically important target, is described. Based upon a target
      selection strategy combining ;low-hanging fruit' and more challenging targets,
      this work has contributed to the body of knowledge of B. anthracis, established
      and developed HTP cloning and expression technologies and tested HTP pipelines.
      Both centres developed ligation-independent cloning (LIC) and expression systems,
      employing custom LIC-PCR, Gateway and In-Fusion technologies, used in combination
      with parallel protein purification and robotic nanolitre crystallization
      screening. Overall, 42 structures have been solved by X-ray crystallography, plus
      two by NMR through collaboration between York and the SPINE partner in Utrecht.
      Three biologically important protein structures, BA4899, BA1655 and BA3998,
      involved in tRNA modification, sporulation control and carbohydrate metabolism,
      respectively, are highlighted. Target analysis by biophysical clustering based on
      pI and hydropathy has provided useful information for future target-selection
      strategies. The technological developments and lessons learned from this project
      are discussed. The success rate of protein expression and structure solution is
      at least in keeping with that achieved in structural genomics programs.

PMID- 17001105
TI  - Structural genomics of the Epstein-Barr virus.
AB  - Epstein-Barr virus is a herpesvirus that causes infectious mononucleosis,
      carcinomas and immunoproliferative disease. Its genome encodes 86 proteins, which
      provided targets for a structural genomics project. After updating the annotation
      of the genome, 23 open reading frames were chosen for expression in Escherichia
      coli, initially selecting for those with known enzyme activity and then
      supplementing this set based on a series of predicted properties, in particular
      secondary structure. The major obstacle turned out to be poor expression and low
      solubility. Surprisingly, this could not be overcome by modifications of the
      constructs, changes of expression temperature or strain or renaturation. Of the
      eight soluble proteins, five were crystallized using robotic nanolitre-drop
      crystallization trials, which led to four solved structures. Although these
      results depended on individual treatment rather than standardized protocols, a
      high-throughput miniaturized crystallization screening protocol was a key
      component of success with these difficult proteins.

PMID- 17001106
TI  - Growth hormone (GH) effects on central fat accumulation in adult Japanese GH
      deficient patients: 6-month fixed-dose effects persist during second 6-month
      individualized-dose phase.
AB  - Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced
      abdominal obesity, which is associated with increased risk of cardiovascular
      complications. We investigated the effects of GH treatment in 27 adult Japanese
      GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD.
      Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a
      double-blind design and the dose was then individualized for each patient
      according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA)
      data were evaluated for percentages of trunk fat, total body fat and lean body
      mass. Serum IGF-I and lipid concentrations were determined at a central
      laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6
      and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day,
      respectively. With the reductions in dose when individualized between weeks 24
      and 48, mean serum IGF-I level was reduced and excessively high values, observed
      in AO patients on the fixed GH dose, were no longer seen. The decrease from
      baseline in trunk fat was similar at week 24 (-3.8 +/- 3.3%, p<0.001) and week 48
      (-3.1 +/- 3.7%, p<0.001), and the difference between changes was not significant.
      Total cholesterol was decreased from baseline by -24 +/- 28 mg/dl (p<0.001) at
      week 24 and -17 +/- 28 mg/dl (p = 0.007) at week 48. Two patients had elevated
      HbA1c levels: one continued GH treatment after a dose reduction and the other
      discontinued due to persistent impaired glucose tolerance. Therefore, excessively
      high IGF-I levels can be avoided by individualized dosing during long-term GH
      treatment. Individualized dosing maintains the decrease in abdominal fat in adult
      Japanese GHD patients and should reduce the cardiovascular risk.

PMID- 17001107
TI  - Predictive value of TSH receptor antibody measurement in Graves' disease is
      independent on the TSH receptor (human or porcine) but depends on the generation
      of the assay used.

PMID- 17001108
TI  - Estrogen receptor alpha regulates insulin sensitivity through IRS-1 tyrosine
      phosphorylation in mature 3T3-L1 adipocytes.
AB  - There are many clinical and experimental reports demonstrating that estrogens and
      insulin interact when affecting their target organs. Estrogen receptors consist
      of two isoforms, estrogen receptors-alpha (ER-alpha) and -beta (ER-beta), but
      their roles in insulin-induced glucose uptake in mature adipose tissue have yet
      to be clarified. To evaluate the roles of ER-alpha, expressed predominantly in
      adipocytes, we have investigated the effects of estradiol (E2), an ER-alpha
      selective agonist (PPT), and its selective antagonist (MPP) on glucose uptake and
      insulin action in 3T3-L1 adipocytes. 3T3-L1 adipocytes were exposed to E2 or PPT
      and/or MPP at different concentrations. The cells were then subjected to 2-deoxy
      D-glucose transport assay, western blot analysis, or RT-PCR analysis. Treatment
      of these cells with E2 or PPT resulted in biphasic effects on glucose transport,
      that is high (10(-5) M or 3 x 10(-6) M each) and low (10(-8) M) doses produced
      inhibition and stimulation, respectively. The favorable effect observed at 10(-8)
      M of E2 was diminished by treatment with MPP. Western bolt analysis revealed that
      these effects of E2, PPT and MPP paralleled the level of IRS-1 tyrosine
      phosphorylation. However, IRS-1 serine phosphorylation, suppressor of cytokine
      signaling (SOCS)-1,-2,-3 and protein tyrosine phosphatase 1B (PTP1B) expression
      did not change compared to control subjects. Our data clearly show that ER-alpha
      contributes to insulin stimulated glucose uptake through regulation of the
      tyrosine phosphorylation of IRS-1 protein.

PMID- 17001109
TI  - Unique treatment policy for well-differentiated thyroid cancer in Japan: results
      of a questionnaire distributed to members of the Japanese Society of Thyroid
      Surgery and the International Association of Endocrine Surgeons.
AB  - Although surgery has been the mainstay of treatment for patients with well
      differentiated thyroid cancer, the extents of thyroid resection and lymph node
      dissection adopted in Japan differ from those in other countries. Furthermore,
      regarding the indications for postoperative radiation therapy and hormonal
      therapy, and treatment modalities for cancer recurrence, there are marked
      discrepancies between Japan and other countries. A questionnaire survey was thus
      conducted among domestic and overseas thyroid surgeons to ascertain the actual
      treatment policy for well-differentiated thyroid cancer in Japan and various
      foreign countries. For small papillary carcinomas of 2.0 cm or less (T1), thyroid
      resection was more extensive in foreign countries than in Japan, although the
      extent of lymph node dissection was limited in the former. For large papillary
      carcinomas exceeding 3.0 cm (T2), on the other hand, total thyroidectomy was the
      treatment of first choice for all overseas respondents, but of only 20% in Japan,
      despite lymph node dissection being more extensive in Japan than in other
      countries. Overseas surgeons were much more likely to favor postoperative TSH
      suppression therapy and high-dose (131)I therapy. For recurrence following
      surgery for papillary thyroid cancer, both domestic and overseas respondents
      indicated surgical resection to be the most common treatment option, and favored
      high-dose (131)I therapy as well. In Japan, however, high-dose (131)I therapy is
      available only in a few institutions. Such limited indications for high-dose
      (131)I therapy in Japan may reflect a discrepancy in the frequency of total
      thyroidectomy, a prerequisite for postoperative high-dose (131)I therapy, between
      Japan and other countries. This is the first questionnaire study conducted in
      both Japan and other countries in relation to treatment modalities for thyroid
      cancer. The results reveal that there is a clear disparity in treatment policies
      between Japan and foreign countries.

PMID- 17001111
TI  - Effect of levothyroxine on total lipid profiles as assessed by analytical
      capillary isotachophoresis in a patient with hypothyroidism.
AB  - The patient was a 51-year-old Japanese female who had been diagnosed with
      hyperlipidemia. At the first medical examination, her serum levels of total
      cholesterol (TC) and triglyceride (TG) were 482 and 205 mg/dl, respectively.
      Since hyperlipidemia was not improved by pravastatin, atorvastatin or niceritrol,
      and since the levels of thyroid-stimulating hormone (TSH) and free T4 were 730
      IU/ml and 0.3 ng/dl, respectively, the patient was diagnosed as secondary
      hyperlipidemia with hypothyroidism. A method for the charge isolation of
      lipoproteins using capillary isotachophoresis (cITP) is proposed as a clinical
      application because it allows us to quantitatively measure electronegative low
      density lipoprotein cholesterol (LDL-C), a potent marker of coronary heart
      disease. After 5 months of treatment with levothyroxine, Serum TC and LDL-C
      levels drastically decreased without statin treatment and high-density
      lipoprotein cholesterol (HDL-C) increased. In the lipoprotein profiles as
      assessed by cITP after treatment with levothyroxin, all HDL-C subfractions were
      increased and fast-migrating LDL/electronegative LDL appeared to be greatly
      reduced after treatment, while the area under the non-modified LDL peak was
      increased. The cITP analysis was able to obtain more information about coronary
      risk factors and may be clinically useful for evaluating the effect of treatment
      with levothyroxine in patients with hypothyroidism and secondary hyperlipidemia.

PMID- 17001110
TI  - The N131S mutation in the von Hippel-Lindau gene in a Japanese family with
      pheochromocytoma and hemangioblastomas.
AB  - von Hippel-Lindau (VHL) disease (VHLD) is a hereditary autosomal dominant
      syndrome that causes various benign and malignant tumors. VHLD is caused by
      mutations in the VHL tumor suppressor gene. Here, we report a mutation in the VHL
      gene in a Japanese family with VHLD type 2A, characterized by pheochromocytoma
      (PHE), and hemangioblastomas (HAB) in both the retina and thoracic spinal cord
      but without renal cell carcinoma (RCC). We identified a heterozygous A to G point
      mutation at the second base of codon 131 of the VHL protein (pVHL). This mutation
      was predicted to convert codon 131 from asparagine to serine (N131S). Although
      most mutations in VHLD type 2A have been detected in the alpha domain of pVHL,
      the present mutated amino acid was located at the region encoding the beta domain
      of pVHL. Previous patients with the N131K or N131T mutation in pVHL developed
      VHLD type 2B with RCC or VHLD type 1 without PHE, respectively. We also
      identified somatic loss of heterozygosity (LOH) at chromosome 3p25-26 in the
      adrenal tumor of the patient. The results of our study suggest that not only the
      location of mutation but also the altered amino acid may be critical for
      determining the clinical phenotype of VHLD. LOH was associated with the
      development of PHE in a patient with the N131S mutation in pVHL.

PMID- 17001112
TI  - IGF binding protein-5 synthesis is regulated by testosterone through
      transcriptional mechanisms in androgen responsive cells.
AB  - We found that androgen and IGF-I up-regulated IGFBP-5 mRNA in androgen-responsive
      normal human fibroblast, which was blocked by co-treatment with 5,6-dichloro-1
      beta-D-ribofuranosyl-benzimidazole, but not cycloheximide. IGFBP-5 promoter
      activity was stimulated by androgen. Nuclear run-on assay revealed that IGFBP-5
      transcripts were increased in response to androgen, which was not enhanced by co
      addition of IGF-I. These results collectively indicate that IGFBP-5 synthesis is
      regulated by androgen through transcriptional mechanisms in androgen responsive
      cells.

PMID- 17001113
TI  - Clonidine induced endothelium-dependent tonic contraction in circular muscle of
      the rat hepatic portal vein.
AB  - Clonidine, an alpha2-agonist, has been shown to be useful in the treatment of
      hepatic portal hypertension in cirrhosis. The mechanism has been attributed to a
      clonidine-induced decrease in sympathetic activity. While clonidine has been
      shown to stimulate the alpha2-adrenoceptors of blood vessels, there is limited
      knowledge of the effects of clonidine on the circular muscle of the hepatic
      portal vein which regulates its blood flow. To investigate clonidine-induced
      contraction of the circular muscle of the hepatic portal vein and to clarify the
      possible role of the endothelium in the contraction, we examined the effects of
      clonidine on the isometric contraction of endothelium-intact and -removed ring
      preparations of the rat hepatic portal vein. In endothelium-intact preparations,
      clonidine caused a concentration-dependent increase in the amplitude of
      contractions. Inhibition of NO synthesis with Nomega-nitro-L-arginine (L-NNA)
      elevated the resting tone, and increased the amplitude of the clonidine-induced
      contractions. Inhibition of cyclooxygenase by diclofenac did not change the
      amplitude of the clonidine-induced contractions observed both in the presence and
      absence of L-NNA. Application of a single concentration of clonidine induced a
      clear increase in amplitude of both twitch and tonic contractions. Twitch and
      tonic contractions induced by clonidine were inhibited by yohimbine. When the
      endothelium was damaged by sodium deoxycholate, tonic contractions induced by
      clonidine were completely suppressed, whereas the increase in twitch contractions
      was not influenced by chemical damage of the endothelium. Neither SKF-96365, a
      nonselective cation channel blocker, nor superoxide dismutase, a free radical
      scavenger, in the presence of catalase, changed the tonic contraction induced by
      clonidine. These results indicate that stimulation of alpha2-adrenoceptors
      enhanced twitch contractions and induced tonic contractions in the circular
      muscle of the rat hepatic portal vein, especially in the absence of NO. The
      latter, but not the former, occurs through an endothelium-dependent pathway.

PMID- 17001114
TI  - Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused
      mesenterial bed.
AB  - Anthocyanins, which are responsible for a variety of bright colors (including
      red, blue, and purple) in fruits, vegetables, and flowers, are consumed as
      dietary polyphenols. Anthocyanin-containing fruits are thought to decrease
      coronary heart disease and are used in anti-diabetic preparations. Diabetes is
      associated with a variety of cardiovascular complications that may be mediated by
      endothelial dysfunction, and so this study was designed mainly to characterize
      the influence of a synthesized anthocyanidin derivative (HK-008) over
      acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from
      rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the
      glucose level as effectively as the same dose of glibenclamide. The aortic
      relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was
      greatly inhibited by glibenclamide (10 microM), and also significantly inhibited
      by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused,
      preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10
      microM), and this enhancement was significantly attenuated by indomethacin (10
      microM). The ACh-induced mesenteric relaxation was impaired by an increase in
      oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1
      U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly
      suppressed by HK-008 (10 microM). These results suggest that HK-008 increases
      endothelium-induced relaxation by suppressing oxidative stress or modulating
      prostanoids signaling. This compound may therefore be useful against certain
      cardiovascular disorders.

PMID- 17001115
TI  - Comparison of multichannel electrogastrograms obtained with the use of three
      different electrode types.
AB  - The goal of the study was to establish if the conductive area size of recording
      electrodes affects the quality of a multichannel electrogastrogram. In twelve
      volunteers (9F, 3M, median age 24 years, range 22-28) on three separate days
      fasted and postprandial four-channel electrogastrograms were registered in
      randomized order with Red Dot class Ag/AgCl electrodes of a type: ;2222'
      (conductive area/total area: 2.00/10.24 cm2, ;2271' 2.54/29.64 cm2, or ;2660'
      11.64/11.64 cm2 (total surface conductive!), and subsequently analyzed with a
      dedicated software. In the case of type 2271 and 2660 the between-electrode
      electrical conductivity improved at the end of the recording relative to the
      basal measurement, whereas type 2222 yielded a stable between-electrode
      electrical conductivity throughout the examination. Despite the differences in
      either the conductive area size or its construction, the analysis of variance on
      parameters describing quantitatively the multichannel electrogastrogram did not
      reveal a superiority of any from among the electrodes tested. Type 2271 was,
      however, rated the less handy among the three electrodes. Multichannel surface
      electrogastrography seems to be technically feasible with any type of high
      quality electrodes, therefore small dimensions and easy handling may favor the
      choice of a particular type for this examination.

PMID- 17001116
TI  - Effect of critical care medicine fellows on patient outcome in the intensive care
      unit.
AB  - BACKGROUND: The impact that physician trainees have on patient outcomes in
      academic adult medical/surgical intensive care units (ICUs) has not been
      adequately assessed. METHOD: All admissions to adult ICUs within the Calgary
      Health Region over a three-year period when a critical care medicine fellow
      (CCMF) was on service were compared to when an attending physician was alone on
      service. Primary outcomes were ICU and in-hospital mortality and length of stay
      (LOS). RESULTS: CCMFs and attending physicians admitted 3,341 patients, while
      attending physicians alone admitted 3,224 patients. There was no difference in
      ICU or in-hospital mortality between the two groups; regression analysis
      determined CCMFs did not affect patient LOS. CONCLUSION: In teaching hospitals
      with adult mixed medical/surgical ICUs, CCMFs do not have an effect on patient
      outcome or LOS. Improved patient outcomes at academic institutions previously
      attributed to the presence of CCMFs may instead be due to institution and patient
      related factors.

PMID- 17001117
TI  - A multilevel analysis of the relationships between selected examinee
      characteristics and United States Medical Licensing Examination Step 2 Clinical
      Knowledge performance: revisiting old findings and asking new questions.
AB  - BACKGROUND: This study examines: (1) the relationships between examinee
      characteristics and United States Medical Licensing Examination Step 2 Clinical
      Knowledge (CK) performance; (2) the effect of gender and examination timing (time
      per item) on the relationship between Steps 1 and 2 CK; and (3) the effect of
      school characteristics on the relationships between examinee characteristics and
      Step 2 CK performance. METHOD: A series of hierarchical linear models (examinees
      nested-in-schools) predicting Step 2 CK scores was fit to the data set. The
      sample included 54,487 examinees from 114 U.S. Liaison Committee on Medical
      Education-accredited medical schools. RESULTS: Consistent with past examinee
      level research, women generally outperformed men on Step 2 CK, and examinees who
      received more time per item generally outperformed examinees who received less
      time per item. Step 1 score was generally more strongly associated with Step 2 CK
      performance for men and for examinees who received less time per item. School
      level characteristics (size, average Step 1 performance) influenced the
      relationship between Steps 1 and 2 CK. CONCLUSION: Both examinee-level and school
      level characteristics are important for understanding Step 2 CK performance.

PMID- 17001118
TI  - Modeling longitudinal performances on the United States Medical Licensing
      Examination and the impact of sociodemographic covariates: an application of
      survival data analysis.
AB  - BACKGROUND: This study models time to passing United States Medical Licensing
      Examination (USMLE) for the computer-based testing (CBT) start-up cohort using
      the Cox Proportional Hazards Model. METHOD: The number of days it took to pass
      Step 3 was treated as the dependent variable in the model. Covariates were: (1)
      gender; (2) native language (English or other); (3) medical school location
      (United States or other); and (4) citizenship (United States or other). RESULTS:
      Examinees were .59 times as likely to pass USMLE if they were trained abroad.
      Additionally, examinees who reported having English as their primary language and
      U.S. citizenship were more likely to ultimately pass USMLE. Finally, though
      gender was also associated with passing USMLE, its practical significance was
      very small. CONCLUSION: Cox regression provides a useful tool for modeling
      performances in a continuous delivery model. Findings suggest that passing the
      USMLE sequence tends to be associated with native English-speaking USMGs who also
      hold U.S. citizenship.

PMID- 17001119
TI  - Educational commission for foreign medical graduates certification and specialty
      board certification among graduates of the Caribbean medical schools.
AB  - BACKGROUND: To determine the variability among Caribbean medical schools in the
      performance of their students against markers of quality. METHOD: The Educational
      Commission for Foreign Medical Graduates (ECFMG) database and the American
      Medical Association (AMA) Masterfile were linked. Analyses were restricted to
      ECFMG applicants, from 1980 to 2000, who attended the 12 Caribbean medical
      schools that produced 200 or more U.S. International Medical School Graduates
      (USIMGs). RESULTS: The schools produced 17,049 USIMG (48% of all USIMGs) and
      5,840 non-USIMG (5% of all non-USIMGs) applicants for ECFMG certification. By
      school, the ECFMG certification rate ranged from 28% to 86% for USIMGs and from
      27% to 82% for non-USIMGs. Specialty Board certification for graduates of these
      schools also varied widely. CONCLUSIONS: Medical schools in the Caribbean play an
      increasingly important role in supplying the U.S. workforce. There is
      considerable variability among them, both in the numbers of physicians they
      produce and the performance of their students against indicators of quality such
      as ECFMG and specialty Board certification.

PMID- 17001120
TI  - A comparison of the characteristics and examination performances of U.S. and non
      U.S. citizen international medical graduates who sought Educational Commission
      for Foreign Medical Graduates certification: 1995-2004.
AB  - BACKGROUND: International medical graduates (IMGs) make up a substantial part of
      the U.S. physician workforce. Unfortunately, little is known about the
      demographic and performance characteristics of these doctors, especially over
      time. METHOD: Educational Commission for Foreign Medical Graduates (ECFMG)
      applicants from 1995-2004 were studied. The characteristics and examination
      performances of U.S. citizen and non-U.S. citizen IMGs were contrasted. RESULTS:
      ECFMG applications from U.S. citizen IMGs have been increasing. Compared to non
      U.S. citizen IMGs, these individuals perform less well on some of the
      certification examinations, especially in the last 5 years, but are more likely
      to eventually achieve certification. Based on those medical students/graduates
      who took the examinations, the performance of U.S. citizen IMGs varied
      considerably from one medical school to another. CONCLUSION: The composition of
      the pool of ECFMG-certified IMGs available for graduate medical education has
      changed over the past 10 years. Shifts in the characteristics and abilities of
      IMGs are likely to have some future impact on health care delivery in the United
      States.

PMID- 17001121
TI  - Medical students' clinical reasoning skills as a function of basic science
      achievement and clinical competency measures: a structural equation model.
AB  - BACKGROUND: The purpose of this study was to investigate the fit of a
      hypothesized model of medical students' diagnostic or clinical reasoning skills
      based on their aptitude for medical school, basic science achievement, and
      clinical competency measures. METHOD: A total of 589 medical students who
      received their MD from 1994 to 2002 participated in this study. Confirmatory
      factor analysis was used to evaluate the fit of theoretical models of clinical
      reasoning using measures of basic science and clinical knowledge. RESULTS: The
      results provided support for a three-factor model of medical student performance
      (Bentler's Comparative Fit Index = .905, standardized root mean squared residual
      = .054, root mean squared error of approximation = .105). The clinical reasoning
      skills of medical students were influenced by an independent relationship between
      latent variables of basic science achievement and clinical competency.
      CONCLUSION: The findings support a theoretical model of diagnostic or clinical
      reasoning that treats the basic science and clinical knowledge of medical
      students as distinct domains.

PMID- 17001122
TI  - The value of basic science in clinical diagnosis.
AB  - BACKGROUND: The role of basic science knowledge in clinical diagnosis is unclear.
      There has been no experimental demonstration of its value in helping students
      recall and organize clinical information. This study examines how causal
      knowledge may lead to better recall and diagnostic skill over time. METHOD:
      Undergraduate medical students learned either four neurological or rheumatic
      disorders. One group learned a basic science explanation for the symptoms. The
      other learned epidemiological information. Both were then tested with the same
      set of clinical cases immediately after learning and one week later. RESULTS: On
      immediate test, there was no difference in accuracy (70% for both groups).
      However, one week later, performance in the epidemiology group dropped to 51%;
      the basic science group only dropped to 62%. CONCLUSIONS: Basic science knowledge
      relating causal knowledge to disease symptoms can improve diagnostic accuracy
      after a delay.

PMID- 17001123
TI  - Literature and medicine: a problem of assessment.
AB  - BACKGROUND: "Literature and medicine" is increasingly common in medical schools
      but not within medical education research. This absence may relate to it not
      being problematizable in the quantitative way in which this psychometrically
      oriented community tends to conceptualize research questions. METHOD: Databases
      were searched using relevant keywords. Articles were evaluated using
      methodologies appropriate to their fields. The resulting information was
      structured around a framework of construct-appropriate assessment methods.
      RESULTS: Literature and medicine is intended to develop skills as potential proxy
      outcomes for important constructs. Proposed tools to assess these skills are
      difficult to evaluate using the field's traditional quantitative framework.
      Methodologies derived from the qualitative tradition offer alternative assessment
      methods. CONCLUSION: The medical education research community should take on the
      challenges presented by literature and medicine. Otherwise, we run the risk that
      the current evaluation system will prevent important constructs from being
      effectively taught and assessed.

PMID- 17001124
TI  - Impact of the United States Medical Licensing Examination Step 2 Clinical Skills
      exam on medical school clinical skills assessment.
AB  - BACKGROUND: Medical schools face a new responsibility to prepare students for the
      United States Medical Licensing Exam Step 2 Clinical Skills (CS) exam. METHOD: We
      conducted semistructured interviews with 25 leaders of medical school clinical
      skills assessments to explore purposes of in-house assessment and the impact of
      the Step 2 CS exam. Interviews were coded to identify major themes. RESULTS:
      Competency assessment, student and curricular feedback, and preparation for the
      licensing exam emerged as major purposes of in-house exams. Participants asserted
      that in-house exams assessed faculty-identified competencies, although not all
      schools had defined competencies. Limited resources made balancing formative and
      summative assessment goals problematic for some schools. Curricular feedback was
      general but valued. All schools, even those that disagreed with aspects of the
      licensing exam, acknowledged their roles in preparing students for the Step 2 CS.
      CONCLUSION: An external licensing requirement engenders debate and motivates
      changes in clinical skills assessment and, in some cases, curricula.

PMID- 17001125
TI  - Medical education: what would the shamans and witches think?

PMID- 17001126
TI  - Fixing healthcare from the inside: teaching residents to heal broken delivery
      processes as they heal sick patients.
AB  - There is a marked gap between the potential of medical science to treat illness
      and injury and the performance of the health care system in which hard-working,
      intelligent, well-trained people put that science to work. Care is available to
      too few, and costs and risks of injury are too high. This is avoidable.
      Experience in Boston, Pittsburgh, Salt Lake City, Seattle, and elsewhere
      indicates that quality can be raised-while risks and costs are dramatically
      reduced-by applying lessons from the highest-performing industrial organizations
      to designing, operating, and improving health care processes. What are these
      lessons? Improve sick processes with the same approaches used to treat patients.
      Specify "normal." When problems in quality, safety, efficiency, responsiveness,
      and the like occur, quickly determine exactly what is abnormal and determine what
      might be causing them. Develop a "treatment plan"-process changes that will
      eliminate or counteract the causal factors. Run the process (or a facsimile) with
      a modified, watching for gaps between actual and expected outcomes. When gaps
      occur, do a new work-up, diagnosis, treatment plan, and test. Lessons in
      designing, operating, and improving processes can be taught just as medical
      expertise is developed. Teach basic frameworks didactically; then, provide hands
      on experience in applying those principles to real problems. Start with simple
      well-bounded situations that can be practiced frequently, with rapid feedback and
      close mentoring before advancing to more complex, less well bounded situations
      that occur less frequently and provide less immediate feedback between action and
      outcome. Incorporate development of process improvement skills into residency
      training so that deepening expertise within specialties is complemented by
      greater skill at integrating functional knowledge into well-integrated care
      processes.

PMID- 17001127
TI  - Assessing the underlying structure of the United States Medical Licensing
      Examination Step 2 test of clinical skills using confirmatory factor analysis.
AB  - BACKGROUND: The purpose of the present study was to assess the fit of three
      factor analytic (FA) models with a representative set of United States Medical
      Licensing Examination (USMLE) Step 2 Clinical Skills (CS) cases and examinees
      based on substantive considerations. METHOD: Checklist, patient note,
      communication and interpersonal skills, as well as spoken English proficiency
      data were collected from 387 examinees on a set of four USMLE Step 2 CS cases.
      The fit of skills-based, case-based, and hybrid models was assessed. RESULTS:
      Findings show that a skills-based model best accounted for performance on the set
      of four CS cases. CONCLUSION: Results of this study provide evidence to support
      the structural aspect of validity. The proficiency set used by examinees when
      performing on the Step 2 CS cases is consistent with the scoring rubric employed
      and the blueprint used in form assembly. These findings will be discussed in
      light of past research in this area.

PMID- 17001128
TI  - Relationships among subcomponents of the USMLE Step 2 Clinical Skills
      Examination, the Step 1, and the Step 2 Clinical Knowledge Examinations.
AB  - BACKGROUND: This research examined relationships between and among scores from
      the United States Medical Licensing Examination (USMLE) Step 1, Step 2 Clinical
      Knowledge (CK), and subcomponents of the Step 2 Clinical Skills (CS) examination.
      METHOD: Correlations and failure rates were produced for first-time takers who
      tested during the first year of Step 2 CS Examination administration (June 2004
      to July 2005). RESULTS: True-score correlations were high between patient note
      (PN) and data gathering (DG), moderate between communication and interpersonal
      skills and DG, and low between the remaining score pairs. There was little
      overlap between examinees failing Step 2 CK and the different components of Step
      2 CS. CONCLUSION: Results suggest that combining DG and PN scores into a single
      composite score is reasonable and that relatively little redundancy exists
      between Step 2 CK and CS scores.

PMID- 17001129
TI  - Competing professionalism values among community-based family physicians.
AB  - BACKGROUND: Professionalism has received considerable attention in recent years,
      mostly within academic settings. Little attention has been given to the
      perspectives of practicing physicians on professionalism. This study was designed
      to determine whether prevailing definitions of and guidelines for professionalism
      accurately reflect the perspectives and experiences of practicing community-based
      family physicians. METHOD: Eighteen practicing family physicians in Seattle were
      recruited from nonacademic settings to participate in focus groups during 2003.
      Transcripts were analyzed for content themes related to professionalism. RESULTS:
      Analysis revealed several tensions among values that the physician participants
      described balancing in their practices. Balancing organizational expectations and
      individual physician or patient values was a major source of tension.
      CONCLUSIONS: Practicing family physicians describe various tensions as they
      attempt to balance their own values with competing values of their patients, the
      organizations for which many work, and stated values of their profession. Such
      tensions among values have seldom been described in past literature and should be
      considered in designing medical curricula at all levels.

PMID- 17001130
TI  - Evaluation of learning outcomes in Web-based continuing medical education.
AB  - BACKGROUND: There has been significant growth in use of Web-based continuing
      medical education (CME) by physicians. A number of evaluation and metareview
      studies have examined the effectiveness of Web-based CME to varying degrees. One
      of the main limitations of this literature has been the lack of systematic
      evaluation across different clinical subject matter areas using standardized Web
      based CME learning formats. METHOD: One group of pretest-postest designs were
      used to evaluate knowledge and self-reported confidence change across multiple
      Web-based courses using a standardized instructional format but comprising
      distinct clinical subject matter. Participants also completed a participant
      satisfaction survey and a self-reported retrospective skill/ability change
      survey. RESULTS: The majority of courses evaluated demonstrated significant pre
      to post knowledge and confidence effect size change, as well as significant self
      reported retrospective practice change. CONCLUSIONS: A Web-based CME
      instructional format comprising multimedia-enhanced learning tutorials
      supplemented by asynchronous computer-mediated conferencing for case-based
      discussions was found to be effective in enhancing knowledge, confidence, and
      self-reported practice change outcomes across a variety of clinical subject
      matter areas.

PMID- 17001131
TI  - Working off the record: physicians' and nurses' transformations of electronic
      patient record-based patient information.
AB  - BACKGROUND: Electronic patient records (EPRs) are increasingly being used in
      health care, but little is known about how EPR-based patient information is used
      in daily care activities, nor about its potential influence on novice training.
      METHOD: Seventy-two physicians and nurses participated in an eight-month study on
      a single pediatric ward. Eighty hours of nonparticipant observations and 20
      interviews were conducted. Data were analyzed using constructivist grounded
      theory and visual rhetoric. RESULTS: Three main features of participant
      interactions with EPR-based information were identified: (1) EPR-based
      information was routinely transformed into paper documents; (2) these
      transformations were organized by profession-specific guiding principles; and (3)
      transformation strategies were learned through an informal curriculum.
      CONCLUSIONS: This study describes how and why health care professionals work
      around EPR-based patient information, and suggests that an EPR's visual
      organization may be incompatible with professional activities. The study
      addresses the socializing implications of these activities, and highlights their
      educational potential.

PMID- 17001132
TI  - Early introduction of clinical skills improves medical student comfort at the
      start of third-year clerkships.
AB  - BACKGROUND: To determine whether introducing clinical skills during the second
      year of medical school, via a competency-based College system approach, improves
      comfort level for medical students entering third-year clinical rotations.
      METHOD: From 2003-2005, two cohorts of third-year medical students at the
      University of Washington were surveyed on their comfort level in the categories
      of history taking, physical examination, communication, and patient care.
      RESULTS: The cohort of students exposed to the College system reported a
      statistically significant greater comfort level in half of the measured areas,
      and in at least one area within each general category. No area of study showed a
      statistically significant decline. CONCLUSION: A competency-based College system
      improves medical student comfort in core clinical skills at the start of the
      third year curriculum.

PMID- 17001133
TI  - Do students do what they write and write what they do? The match between the
      patient encounter and patient note.
AB  - BACKGROUND: Patient notes are used for a variety of purposes in health care.
      Medical students are taught the structure of patient notes early in training.
      Review of patient notes are then used to assess synthesis and integration of
      patient information. It is critical that the information in the note accurately
      and completely represents the student-patient encounter. METHOD: The authors
      reviewed videotapes of students in three standardized-patient based scenarios and
      compared what occurred during the physical examination with the subsequent
      documentation in the patient note. RESULTS: In all, 207 encounter-note pairs were
      reviewed. Only 8 (4%) of the notes completely and accurately represented what
      occurred during the encounter. Problems with underdocumentation,
      overdocumentation, and inaccurate documentation of physical findings were seen
      for all three patient scenarios. CONCLUSIONS: These findings highlight the need
      to teach and assess both data gathering skills and written documentation of
      findings in medical training.

PMID- 17001134
TI  - Procedural and interpretive skills of medical students: experiences and attitudes
      of third-year students.
AB  - BACKGROUND: Recent data do not exist on medical students' performance of and
      attitudes toward procedural and interpretive skills deemed important by medical
      educators. METHOD: A total of 171 medical students at seven medical schools were
      surveyed regarding frequency of performance, self-confidence, and perceived
      importance of 21 procedural and interpretive skills. RESULTS: Of the 122
      responding students (71% response rate), a majority had never performed lumbar
      puncture, thoracentesis, paracentesis, or blood culture, and students reported
      lowest self-confidence in these skills. At least one-quarter of students had
      never performed phlebotomy, peripheral intravenous catheter insertion, or
      arterial blood sampling. Students perceived all 21 skills as important to learn
      and perform during medical school. CONCLUSION: Through the third year of medical
      school, a majority of students had never performed important procedures, and a
      substantial minority had not performed basic procedures. Students had low self
      confidence in skills they rarely performed, but perceived all skills surveyed as
      important.

PMID- 17001135
TI  - Are discharge summaries teachable? The effects of a discharge summary curriculum
      on the quality of discharge summaries in an internal medicine residency program.
AB  - BACKGROUND: Interns are often required to dictate discharge summaries without
      formal training. We investigated the impact of a curriculum aimed at improving
      the quality (i.e., complete, organized, succinct, internally consistent, and
      readable) of interns' discharge summaries. METHOD: Fifty-nine medicine interns
      were randomized to a: (1) control group; (2) discharge summary curriculum; or (3)
      curriculum plus individualized feedback. Pre- and post-intervention, seven
      discharge summaries were graded using a 9-item instrument. T-tests, analysis of
      covariance, and effect sizes assessed group differences. RESULTS: There were
      multiple, significant within-group improvements for the intervention groups and
      between group differences post-intervention. The average effect size was large
      when the curriculum plus feedback group was compared to the control group (.70)
      and moderate when compared to the curriculum only group (.36). CONCLUSIONS:
      Interns who received instruction on discharge summary skills improved the quality
      and of their discharge summaries. Adding feedback to the curriculum provided more
      benefit.

PMID- 17001136
TI  - Psychometric characteristics and response times for content-parallel extended
      matching and one-best-answer items in relation to number of options.
AB  - BACKGROUND: This study investigated the impact of item format and number of
      options on the psychometric characteristics (p values and biserials) and response
      times for multiple-choice questions (MCQs) appearing on Step 2 of the United
      States Medical Licensing Examination. METHOD: In all, 192 MCQ items were used in
      the study. Each item was presented in two formats: in a two-item extended
      matching set and as an independent item. For the extended matching format, there
      were two versions: a base version that included all options (10 to 26) and an 8
      option version. For the independent-item format, there were three versions: a
      base version that included all options, and 8-option and 5-option versions
      created by a group of physicians that selected options without information about
      examinee performance. All items were embedded in unscored sections of the 2005-06
      Step 2 test forms. RESULTS: Versions of items with more options were harder and
      required more testing time; no differences in item discrimination were observed.
      Mean response times for items presented in the extended-matching format were
      lower than for those presented as independent items, primarily because of shorter
      response times for the second item presented in a set. CONCLUSION: Use of the
      extended-matching format and smaller numbers of options per item (and more items)
      should result in more efficient use of testing time and greater score precision
      per unit of testing time.

PMID- 17001137
TI  - Use of the mini-clinical evaluation exercise to rate examinee performance on a
      multiple-station clinical skills examination: a validity study.
AB  - BACKGROUND: Multivariate generalizability analysis was used to investigate the
      performance of a commonly used clinical evaluation tool. METHOD: Practicing
      physicians were trained to use the mini-Clinical Skills Examination (CEX) rating
      form to rate performances from the United States Medical Licensing Examination
      Step 2 Clinical Skills examination. RESULTS: Differences in rater stringency made
      the greatest contribution to measurement error; more raters rating each examinee,
      even on fewer occasions, could enhance score stability. Substantial correlated
      error across the competencies suggests that decisions about one scale unduly
      influence those on others. CONCLUSIONS: Given the appearance of a halo effect
      across competencies, score interpretations that assume assessment of distinct
      dimensions of clinical performance should be made with caution. If the intention
      is to produce a single composite score by combining results across competencies,
      the presence of these effects may be less critical.

PMID- 17001138
TI  - Effects of case characteristics on encounter time in a high-stakes standardized
      patient examination.
AB  - BACKGROUND: Data from national surveys indicate that patient characteristics
      could influence the time spent by physicians interviewing and assessing patients.
      The purposes of this investigation were to gather information regarding the
      relationship between encounter time and case characteristics for simulated
      clinical encounters and to provide evidence that the time provided to gather data
      was adequate. Timing data was extracted from United States Medical Licensing
      Examination Step 2 Clinical Skills. METHOD: To test the relative effects of case
      characteristics on encounter time, an analysis of variance was conducted with
      encounter time as the dependent variable and case characteristics as the
      independent variables. RESULTS: Mean encounter times were computed based on the
      case characteristics. Station format (history only, history and physical
      examination, telephone cases) predicted the most variance in encounter time
      (16%). CONCLUSIONS: The extent to which examination content is balanced from
      administration to administration ensures a mix of cases that provides adequate
      time limits for examinees.

PMID- 17001139
TI  - American Indians and Alaska Natives: how do they find their path to medical
      school?
AB  - BACKGROUND: American Indians and Alaska Natives (AI/ANs) remain underrepresented
      in the medical profession. This study sought to understand the supports and
      barriers that AI/AN students encountered on their path to successful medical
      school entry. METHOD: The research team analyzed qualitative semistructured, one
      on-one, confidential interviews with 10 AI/AN medical students to identify
      salient support and barrier themes. RESULTS: Supports and barriers clustered in
      eight categories: educational experiences, competing career options and
      priorities, health care experiences, financial factors, cultural connections,
      family and friends, spirituality, and discrimination. Some of the most notable
      findings of this study include the following: (1) students reported financial
      barriers severe enough to constrain participation in the medical school
      application process, and (2) spirituality played an important role as students
      pursued a medical career. CONCLUSION: Promoting AI/AN participation in medical
      careers can be facilitated with strategies appropriate to the academic,
      financial, and cultural needs of AI/AN students.

PMID- 17001140
TI  - Medical school admissions: enhancing the reliability and validity of an
      autobiographical screening tool.
AB  - BACKGROUND: Most medical school applicants are screened out preinterview. Some
      cognitive scores available preinterview and some noncognitive scores available at
      interview demonstrate reasonable reliability and predictive validity. A reliable
      preinterview noncognitive measure would relax dependence upon screening based
      entirely on cognitive tendencies. METHOD: In 2005, applicants interviewing at
      McMaster University's Michael G. DeGroote School of Medicine completed an
      offsite, noninvigilated, Autobiographical Submission (ABS) preinterview and
      another onsite, invigilated, ABS at interview. Traditional and new ABS scoring
      methods were compared, with raters either evaluating all ABS questions for each
      candidate in turn (vertical scoring-traditional method) or evaluating all
      candidates for each question in turn (horizontal scoring-new method). RESULTS:
      The new scoring method revealed lower internal consistency and higher interrater
      reliability relative to the traditional method. More importantly, the new scoring
      method correlated better with the Multiple Mini-Interview (MMI) relative to the
      traditional method. CONCLUSIONS: The new ABS scoring method revealed greater
      interrater reliability and predictive capacity, thus increasing its potential as
      a screen for noncognitive characteristics.

PMID- 17001141
TI  - The Professionalism Mini-evaluation Exercise: a preliminary investigation.
AB  - BACKGROUND: As the evaluation of professional behaviors has been identified as an
      area for development, the Professionalism Mini-Evaluation Exercise (P-MEX) was
      developed using the mini-Clinical Examination Exercise (mini-CEX) format. METHOD:
      From a set of 142 observable behaviors reflective of professionalism identified
      at a McGill workshop, 24 were converted into an evaluation instrument modeled on
      the mini-CEX. This instrument, designed for use in multiple settings, was tested
      on clinical clerks in medicine, surgery, obstetrics and gynecology, psychiatry,
      and pediatrics. In all, 211 forms were completed on 74 students by 47 evaluators.
      RESULTS: Results indicate content and construct validity. Exploratory factor
      analysis yielded 4 factors: doctor-patient relationship skills, reflective
      skills, time management, and interprofessional relationship skills. A decision
      study showed confidence intervals sufficiently narrow for many measurement
      purposes with as few as 8 observations. Four items frequently marked below
      expectations may be identifiers for "problem" students. CONCLUSION: This
      preliminary study suggests that the P-MEX is a feasible format for evaluating
      professionalism in clinical training.

PMID- 17001142
TI  - Performance outcomes associated with medical school community service.
AB  - BACKGROUND: Providing medical students with community service opportunities
      during medical school is believed to foster altruism. Little is known whether
      voluntary community service is associated with students' academic and clinical
      skill performance. This study examined the relationship between students'
      volunteer community service hours during medical school and their medical school
      academic performance, measures of clinical skills, and residency performance.
      METHOD: Subjects were 2001 and 2002 graduates of the institution. Performance
      measures were: United States Medical Licensing Examination (USMLE) Step 2 score,
      grade point average, fourth-year clinical skills examination scores, and two
      types of residency director assessments. Associations between performance
      measures and community service hour categories were analyzed using descriptive
      statistics, chi-square, and t-tests. RESULTS: Students in the highest service
      group (>/=18.5 hours) had significantly higher grade point averages, USMLE Step 2
      scores, and scores on both residency director assessment when compared to
      students with no community service hours. CONCLUSIONS: Community service
      involvement in medical school appears associated with medical school academic and
      residency performances.

PMID- 17001143
TI  - Medical student professionalism: are we measuring the right behaviors? A
      comparison of professional lapses by students and physicians.
AB  - BACKGROUND: Examining the relationship between unprofessional behaviors observed
      in medical students and those manifested by physicians is important in
      determining whether medical school faculty are observing and reporting behaviors
      relevant to medical practice. METHOD: This study compares the relationship
      between unprofessional behaviors identified in students at our medical school
      through Early Concern Notes, and behaviors for which physicians were sanctioned
      by our state medical board. RESULTS: The majority of reports in both groups were
      related to lapses in professional responsibility and integrity, and the specific
      behaviors identified in the groups were similar. A smaller number of reports in
      both groups were related to pursuit of excellence or personal interactions.
      CONCLUSION: There are common features to the professional shortcomings seen in
      students at our medical school and practicing physicians in our state. These
      similarities add credibility to our faculty's observations, and reinforce the
      relevance of monitoring such behaviors in future physicians.

PMID- 17001144
TI  - Impact of a teaching scholars program.
AB  - BACKGROUND: Researchers employ various approaches to evaluate teaching scholars
      programs (TSPs). We interviewed secondary beneficiaries of the TSP. METHOD:
      During an interview, TSP graduates identified individuals and/or groups whom they
      felt were affected as a result of their TSP participation. At least one
      individual from each type of these identified beneficiaries was interviewed.
      Quantitative results were summarized descriptively and qualitative comments coded
      through a consensus process. RESULTS: Thirty-six (88%) of TSP participants were
      interviewed. From their responses, 50 beneficiaries were interviewed. Sixty-eight
      percent of beneficiaries identified that, as a result of TSP, the scholars became
      better teachers and educational scholars and enhanced educational scholarship,
      programs, teaching, mentoring, and leadership in departments. Eighty-nine percent
      identified educational projects emanating from their contact with the scholar.
      CONCLUSION: Beneficiaries validated that the TSP produced better teachers and
      scholars. The impact in scholarship validated the importance of completing a
      project as part of the TSP. TSP also enhanced networking and educational
      resources for departments.

PMID- 17001145
TI  - A longitudinal study of internal medicine residents' retention of advanced
      cardiac life support skills.
AB  - BACKGROUND: Internal medicine residents must be competent in Advanced Cardiac
      Life Support (ACLS) for board certification. Traditional ACLS courses have
      limited ability to enable residents to achieve and maintain skills. Educational
      programs featuring reliable measurements and improved retention of skills would
      be useful for residency education. METHOD: We developed a training program using
      a medical simulator, small-group teaching and deliberate practice. Residents
      received traditional ACLS education and subsequently participated in four two
      hour educational sessions using the simulator. Resident performance in six
      simulated ACLS scenarios was assessed using a standardized checklist. RESULTS:
      After the program, resident ACLS skill improved significantly. The cohort was
      followed prospectively for 14 months and the skills did not decay. CONCLUSIONS:
      Use of a simulation-based educational program enabled us to achieve and maintain
      high levels of resident performance in simulated ACLS events. Given the
      limitations of traditional methods to train, assess and maintain competence,
      simulation technology can be a useful adjunct in high-quality ACLS education.

PMID- 17001146
TI  - Comparing traditional and computer-based training methods for standardized
      patients.
AB  - BACKGROUND: The use of computer-based training programs in medicine is
      widespread. To date, however, there has been little or no research conducted to
      explore how these self-delivered educational programs can be applied to the
      training of standardized patients (SPs). The purpose of this study was to compare
      a traditional SP training technique with one that was based on computer-based
      delivery of case materials and checklist-based scoring criteria. METHOD: Ten SPs
      were trained to portray 1 of 5 cases. The SPs were paired by case and then
      randomly assigned to either an experimental (computer-based training) or control
      (traditional trainer-based training) group. Forty medical students completed a 5
      station clinical skills assessment where they encountered both computer- and
      trainer-trained SPs. Portrayal fidelity and documentation accuracy was assessed
      via videotape review of the individual encounters. RESULTS: With reference to
      checklist scoring discrepancies, documentation accuracy was significantly greater
      for those SPs who were trained using the computer-based delivery method.
      Likewise, based on a summary measure of portrayal fidelity, the performances of
      traditionally trained SPs were quite realistic but, nevertheless, less dependable
      than those for the computer-trained group. CONCLUSION: The use of computer
      assisted educational programs to train SPs is effective and can lead to
      performance fidelity gains as well as improved accuracy with respect to the
      documentation of history taking and physical examination skills.

PMID- 17001147
TI  - Teaching foundational physical examination skills: study results comparing lay
      teaching associates and physician instructors.
AB  - BACKGROUND: The purpose of this pilot study was to determine differences in the
      physical exam skills of first-year medical students learning physical exam
      exclusively from standardized physical examination teaching associates (SPETAs)
      or physician faculty. METHOD: In all, 144 first-year medical students were
      randomized to receive SPETA or physician-led physical examination instruction.
      Students participated in an OSCE assessment immediately following the end of the
      curriculum block. RESULTS: SPETA-trained students performed equivalently to
      physician faculty trained students across all stations with a mean of 82.9%
      versus 81.2% (p = .226). Students taught by SPETAs performed significantly better
      on the abdominal OSCE with a mean score of 88.8%, while physician faculty taught
      students had a mean score of 85.4% (p = .03). CONCLUSION: Findings from this
      study suggest that SPETAs can effectively teach foundational physical examination
      skills to medical students at a similar and sometimes better performance level as
      physician faculty.

PMID- 17001148
TI  - Which U.S. medical graduates plan to become specialty-board certified? Analysis
      of the 1997-2004 national association of American Medical Colleges Graduation
      Questionnaire database.
AB  - BACKGROUND: Predictors of U.S. allopathic medical-school graduates' board
      certification plans have not been characterized. METHOD: Using multivariable
      logistic regression, graduates' responses to 11 questions on the 1997-2004
      Association of American Medical Colleges Graduation Questionnaire were analyzed
      to identify independent predictors of plans for specialty-board certification.
      RESULTS: The proportion of 108,408 graduates planning specialty-board
      certification decreased from 97.3% in 1997 to 88.4% in 2004. Among 101,805
      (93.9%) graduates with complete data, graduates who were Hispanic, rated their
      clinical clerkships, quality of medical education, and confidence in clinical
      skills more highly, had any debt, and planned "University-faculty" careers were
      more likely to plan becoming board certified. Females, Asians/Pacific Islanders,
      and graduates who planned to practice in underserved areas, planned "other"
      nonclinical-practice careers, and graduated with MD/other (non-PhD) degrees were
      less likely to plan becoming board certified. CONCLUSION: Specialty-board
      certification does not appear to be among the professional goals for a growing
      proportion of U.S. medical graduates.

PMID- 17001150
TI  - Patterns of stromal invasion in ovarian serous tumors of low malignant potential
      (borderline tumors): a reevaluation of the concept of stromal microinvasion.
AB  - Stromal-epithelial patterns of invasion in serous tumors of the ovary have been
      subclassified as destructive and nondestructive. By definition, well
      differentiated serous tumors featuring destructive stromal invasion are
      classified as low-grade serous carcinomas whereas those with either no stromal
      invasion or stromal microinvasion are classified as serous tumors of low
      malignant potential (S-LMP). The histologic features of stromal microinvasion in
      ovarian S-LMP have been addressed in a variety of studies, but controversy
      persists regarding diagnostic criteria and prognostic significance, particularly
      in patients with high-stage disease. In addition, a subset of otherwise typical S
      LMP has patterns of invasion that are not classic destructive invasion and do not
      meet the current diagnostic criteria for stromal microinvasion because of either
      qualitative features or size restrictions. To further evaluate the full
      histologic spectrum of stromal-epithelial patterns of invasion in otherwise
      typical S-LMP, we examined a series of 60 ovarian S-LMP (34 FIGO stage I; 26 FIGO
      stages II, III, and IV) with stromal-epithelial alterations not meeting criteria
      for classic destructive invasion. This group of cases included those meeting the
      definition of microinvasion and a subset that would be excluded based on size
      measurements or unusual qualitative features, but did not exhibit significant
      stromal reaction. Five patterns of invasion were identified: individual
      eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching
      papillae, inverted macropapillae, and micropapillae. Individual, discrete
      aggregates of invasive epithelium ranged from 1 to 12 mm (mean, 1.4 mm) in
      greatest linear dimension as measured by conventional methods. The number of
      discrete foci ranged from 1 to greater than 10; in 7 tumors (12%), the invasive
      foci were diffusely scattered throughout the stroma without discrete aggregates.
      These stromal-epithelial alterations were associated with disease progression
      and/or death due to disease in 9 of 50 (18%) patients with follow-up (mean, 92.5
      mo) and were covariant with other adverse prognostic features (invasive implants,
      nodular lymph node aggregates, high stage, and unresectable disease). Disease
      progression was most strongly linked to the presence of micropapillae, but the
      majority of patients with adverse outcome had the more common, classic stromal
      epithelial patterns associated with microinvasion (ie, individual cells, cell
      clusters, and simple papillae). Neither size of the largest contiguous aggregate
      nor extent of stromal involvement correlated with outcome. Classic microinvasion
      disproportionately occurred in patients presenting during pregnancy (P<0.0001),
      and was not associated with adverse outcome in that setting, but follow-up was
      limited. Based on the cumulative outcome data, the presence of stromal-epithelial
      patterns of invasion distinct from classic destructive invasion in otherwise
      typical S-LMP stratifies patients at long-term risk for disease progression, but
      does not warrant a diagnosis of carcinoma or a change in current management
      schemes. Maintaining classification as a serous tumor of low malignant potential
      (serous borderline tumor) with stromal invasion seems appropriate even in the
      presence of diffuse stromal involvement or discrete aggregates measuring greater
      than 3 (or 5) mm. As the stromal-epithelial alteration featuring micropapillae
      may represent a comparatively higher-risk lesion with a clinical course analogous
      to that of low-grade serous carcinoma, pathologists should identify this specific
      stromal-epithelial pattern in the diagnostic report until sufficient data is
      acquired to form more definitive conclusions regarding its prognosis.

PMID- 17001151
TI  - Incidental carcinomas in prophylactic specimens in BRCA1 and BRCA2 germ-line
      mutation carriers, with emphasis on fallopian tube lesions: report of 6 cases and
      review of the literature.
AB  - The identification of germ-line mutations in 2 genes (BRCA1 and BRCA2)
      responsible for the majority of hereditary ovarian cancers has led an increasing
      number of women carriers of these mutations to undergo prophylactic oophorectomy
      (PO) to reduce their risk of subsequent ovarian carcinoma. A large number of
      unexpected, clinically occult neoplasms are thus being discovered. Up to December
      2004, the Medical Genetics Service of the National Cancer Institute in Milan,
      Italy, has tested 756 probands from breast and/or ovarian cancer families for
      BRCA1 and BRCA2 germ-line mutations. Molecular screening of family members led to
      the identification of 344 female carriers of BRCA1 (239) or BRCA2 (105) germ-line
      mutations. Of the 186 potentially eligible women (37 of whom had tested positive
      for BRCA1 and 13 for BRCA2 mutation), 50 (26.8%) chose to undergo PO. Six
      clinically occult primary gynecologic malignancies (2 stage IIIC serous
      carcinomas of the ovary, 3 in situ serous carcinomas of the fallopian tube, and 1
      stage IIB invasive serous carcinoma of the fallopian tube) and 1 occult ovarian
      metastasis from breast carcinoma were identified in the PO specimens of 7 women
      (all BRCA1 mutated). Four of the patients with occult primary gynecologic cancers
      are alive without disease 129, 87, 38, and 7 months after PO, respectively. One
      of the 2 patients with primary ovarian cancer and the single patient with tubal
      invasive carcinoma are alive with recurrent disease 83 and 20 months after PO,
      respectively. In addition, one of the patients whose PO specimen did not show any
      malignancy presented with stage IIIC tubal carcinoma 77 months after PO. The
      relatively high number of tubal neoplasms found at PO in this group of patients
      underlines the linkage between mutation and the risk of developing tubal cancer,
      and stresses the need to include removal of the entire tubes at the time of PO
      and of thoroughly evaluating the specimens at the microscopic level. The
      upstaging of all 3 invasive carcinomas after staging surgery, and the late
      recurrence and persistence of 2 of them despite treatment indicate that small
      size of the tumors should not preclude therapy.

PMID- 17001152
TI  - Immunohistochemical staining of precursor forms of prostate-specific antigen
      (proPSA) in metastatic prostate cancer.
AB  - Precursors of prostate-specific antigen (proPSA) have been previously shown to be
      more concentrated in prostate cancer tissue. This study characterizes the
      immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer
      compared with prostate specific antigen (PSA) and prostatic acid phosphatase
      (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate
      carcinoma and control tissues, was used. IHS, using monoclonal antibodies against
      proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA),
      native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were
      specific for both benign and malignant prostatic glandular tissue. IHS with [-5/
      7]pPSA showed the least number of cases with negative staining (3%), and the most
      number of cases with moderate or strong staining (76%). In the 60 cases where all
      4 stains could be evaluated, none of them were negative for proPSA and positive
      for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed
      IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and
      PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases
      showing positivity for the marker. Even cases that were negative for PSA and PAP,
      were reactive for proPSA. Such enhanced detection is particularly important in
      poorly differentiated carcinomas involving metastatic sites where prostate
      carcinoma is a consideration. A panel of markers, including proPSA, should be
      performed when metastatic prostate carcinoma is in the differential diagnosis.

PMID- 17001153
TI  - The clear cell variant of solid pseudopapillary tumor of the pancreas: a
      previously unrecognized pancreatic neoplasm.
AB  - Solid pseudopapillary tumor is a rare but distinctive pancreatic neoplasm whose
      cell phenotype remains a mystery. We report 3 cases of a previously undescribed
      variant of solid pseudopapillary tumor of the pancreas composed almost entirely
      of multivacuolated clear cells (>90%). The cytoplasmic vacuoles did not contain
      glycogen, mucin, or lipid but seemed to be formed by dilatation of the
      endoplasmic reticulum and mitochondria. The tumors displayed prominent trabeculae
      and a solid growth pattern but lacked the characteristic pseudopapillary pattern
      of the classical solid pseudopapillary tumor. In contrast, the clinical features,
      gross characteristics, and immunoprofile were similar to those of classical solid
      pseudopapillary tumor. Two of the patients were young adult females with well
      demarcated tumors involving the body and tail of the pancreas. Tumor cells showed
      immunoreactivity for vimentin, CD10, CD56, synaptophysin, and nuclear
      accumulation of beta catenin. In 2 patients, 1 male and 1 female, the tumors were
      discovered incidentally. Despite vascular invasion in one of the tumors all 3
      patients are disease free after distal pancreatectomy. Clues to distinguish the
      clear cell variant of solid pseudopapillary tumor from endocrine pancreatic tumor
      composed of clear cells, clear and foamy cell variants of ductal carcinoma,
      metastatic renal cell carcinoma, serous cystadenoma and ectopic adrenocortical
      nodules are provided.

PMID- 17001154
TI  - Solid and pseudopapillary tumor of the pancreas--review and new insights into
      pathogenesis.
AB  - Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms that occur
      mostly in young women. Despite of a low malignant potential, 10% to 15% of the
      cases have aggressive behavior with metastatic dissemination possibly leading to
      death. To date, no pathological factor can reliably predict the outcome of these
      tumours. Galectin-3, a major actor in the carcinogenesis of pancreatic ductal
      adenocarcinoma, has not been investigated in SPT. The presence of progesterone
      receptors is frequently reported in SPT, whereas that of estrogen receptor (ER)
      is unclear. We studied 5 cases of SPT consisting of 4 pancreatic tumors and 1
      metastatic case. The morphological distinctive feature of metastatic nodules was
      the presence of polygonal or spindle cells with pleiomorphic nuclei and high
      mitotic count exhibiting a diffuse, infiltrative growth pattern. We found a
      strong expression of galectin-3 in all SPTs, whereas, interestingly, it was lower
      in metastatic nodules. Conversely, no galectin-3 expression was found in normal
      pancreatic endocrine cells or in neuroendocrine tumors. We suggest therefore that
      galectin-3 is a useful marker to distinguish SPT from neuroendocrine tumor, and
      also indicator of behavior because its low expression is associated with
      metastatic spreading. Moreover, the presence of galectin-3 in both SPT and
      pancreatic ducts rises the hypothesis of a posible ductal origin of these tumors.
      Specific antibodies for anti-ERalpha and anti-ERbeta demonstrated a strong
      expression of ERbeta whereas ERalpha was not detected. In conclusion, the present
      study brings the first evidence of the involvement of galectin-3 in SPT but also
      brought up clues which allowed to reconcile previously conflicting results on the
      presence of ER.

PMID- 17001155
TI  - Microsatellite instability in nasopharyngeal and lymphoepithelial carcinomas of
      the head and neck.
AB  - Lymphoepithelial carcinoma (LEC) is a descriptive diagnosis for an
      undifferentiated carcinoma that has a typical morphologic appearance of large
      vesicular cells with prominent nucleoli and infiltrating lymphocytes. Tumors with
      this histopathologic appearance in the head and neck can be categorized as either
      those that occur in endemic areas, such as Southeast Asia and are associated with
      Epstein-Barr virus (EBV) infection, or those that occur in other countries and
      are less commonly associated with EBV. The molecular changes in endemic EBV
      related LEC have been fairly well studied and include both alterations in tumor
      suppressor genes and 1 report of high levels of microsatellite instability. In
      nonendemic LECs arising in western countries, there is very little data related
      to molecular mutational profiles. In this study, we examined 19 cases of LEC from
      the United States for evidence of microsatellite instability at the DNA level and
      for alterations in the DNA mismatch repair (MMR) system at the
      immunohistochemical staining level. Only 3/19 cases showed high-level
      microsatellite instability and only 1 of these showed an alteration in the DNA
      MMR protein expression hMLH1. These data suggest that alterations in DNA MMR
      system are not a common mechanism of tumorigenesis in LEC of the head and neck in
      a nonendemic country.

PMID- 17001156
TI  - Pleomorphic giant cell adenocarcinoma of the prostate: report of 6 cases.
AB  - Pleomorphic tumors with giant cells have been described in a variety of primary
      sites. However, only a few cases have been described among prostatic carcinomas
      with only 1 on diagnostic biopsy material. Five cases were retrieved from the
      consultation files of one of the authors. One of the cases was retrieved from the
      surgical pathology files at our institute. Patient ranged in age from 59 to 76
      years (mean=65.8 y). The diagnosis was made on needle biopsy (n=3), urethral
      biopsy (n=1), transurethral resection (n=1), or radical prostatectomy (n=1). In
      all cases, giant, bizarre, anaplastic cells were present. In 4 of the cases,
      marked pleomorphism occupied 5% of the specimen, with 20% and 70% bizarre giant
      cells in the other 2 cases. In one case, the bizarre cells had atypical mitotic
      figures, with other cases showing no mitoses in the markedly pleomorphic cells.
      In addition to the pleomorphic giant cell component, multiple coexistent
      histologic components were seen including Gleason score 9 conventional prostate
      cancer (n=6), small cell carcinoma (n=1), squamous carcinoma (n=1), and prominent
      ductal adenocarcinoma differentiation with intraductal spread (n=1).
      Immunohistochemically, 4 cases were for negative for prostate-specific antigen in
      the giant cells, 1 had 5% staining, and the other had 50% positivity in the giant
      cells. Staining for prostate-specific antigen in the conventional prostate
      carcinoma component was 1%, 5%, 20%, 50%, 100%, and 100%. The bizarre giant cells
      were strongly positive for cytokeratins AE1/AE3 and/or Cam 5.2 (n=3). Two cases
      had a history of conventional prostate cancer 4 years before the giant cell
      component, 1 treated with Lupron and the other with radiation. Follow-up after
      diagnosis of the giant cell component: Case 1: dead in 1 year of disease; Case 2:
      progressive metastases in 2 years; Case 3: alive at 1 year with disease; Case 4:
      large perineal recurrence after brachytherapy at 3 years; Case 5: radical
      prostatectomy with extraprostatic extension and seminal vesicle invasion; and
      Case 6: alive at 3 months, free of disease. Conventional prostate cancer, even
      when very high grade, typically consists of cells with relatively uniform nuclei.
      Our study expands the histology described in prostate cancer to include in very
      rare cases with prominent pleomorphism and bizarre giant cells. This giant cell
      component heralds a particularly aggressive clinical outcome.

PMID- 17001157
TI  - Primary testicular lesions are associated with testicular germ cell tumors of
      adult men.
AB  - The present study aims to establish the nature and frequency of testicular
      lesions in the parenchyma adjacent to testicular germ cell tumors (TGCT) to
      improve understanding of the factors involved in the development of testicular
      cancer. Fifty-three cases of TGCT that were fixed in both neutral-buffered
      formalin and Bouin solution, allowing for the nuclear characterization of Sertoli
      cells (SCs), were included in this study. In each case, at least 3 sections of
      different areas of preserved parenchyma surrounding the TGCT were studied. We
      found Leydig cell hyperplasia, microlithiasis, angiopathy, adenomatous
      hyperplasia of the rete testis, SC nodules, SC dysgenesis and involution, SC-only
      tubules, tubular atrophy, adluminal compartment lesions, hypospermatogenesis
      associated with spermatocyte sloughing, spermatogonial maturation arrest, and
      hypertrophic and multinucleated spermatogonia. These lesions were found in
      regions both adjacent and far away from the tumoral mass, and abnormal
      seminiferous tubules were found intermingled with those showing complete
      spermatogenesis, suggesting that these lesions are primary and existed before the
      development of the tumor. Our study suggests that SCs might play a more important
      role in the development of testicular tumors than previously thought. Our data
      supports the hypothesis that there is an abnormal differentiation of SCs, caused
      either by genetic anomalies or by environmental agents during fetal life. This
      abnormal SC differentiation may cause not only primary spermatogenesis failure
      and spermatogenesis arrest at different levels, but may also contribute to the
      poor differentiation of gonocytes into spermatogonia. The abnormal gonocyte
      differentiation might favor the development of dysplastic germ cells that may
      later transform into intratubular germ cell neoplasia, unclassified type.

PMID- 17001158
TI  - Hyalinizing trabecular adenoma of the thyroid revisited: a histologic and
      immunohistochemical study of thyroid lesions with prominent trabecular
      architecture and sclerosis.
AB  - BACKGROUND: Since its description, hyalinizing trabecular adenoma (HTA) of the
      thyroid has been a controversial entity. Some have considered it a unique entity,
      some have considered it a variant of papillary carcinoma (PC), and still others
      have considered it a nonspecific pattern that may be seen with a variety of
      thyroid lesions. Complicating the matter, studies demonstrating metastases have
      shown entities that do not appear to be HTAs as originally described, and
      molecular studies showing changes of PC have used methods that are not specific.
      This study reviews our experience with thyroid lesions that showed at least some
      histologic features of HTA and presents the immunohistochemical findings for
      these lesions using antibodies employed for the diagnosis of PC. DESIGN: Our
      files were reviewed for all thyroid resection reports describing lesions with
      hyalinized or sclerotic stroma and a trabecular architecture within the diagnosis
      or diagnostic comment. All cases were reviewed and classified as either HTA or as
      different lesions based upon histologic features. Immunohistochemistry with
      antibodies to HBME1, CK19 and p63 was performed with all lesions and with a
      series of controls. RESULTS: Eighteen thyroid lesions with prominent sclerosis or
      hyalinization and trabecular architecture were identified. Only 4 of these were
      found to completely match the histologic and cytologic descriptions of HTA by HE
      review. The other cases showed histologic features more compatible with other
      diagnoses including cellular adenomatoid nodule (5), follicular adenoma (4),
      follicular variant of PC (FVPC) (3), and epithelial neoplasm with features of
      FVPC (2). All HTAs lacked immunoreactivity for HBME1, CK19 and p63. All cases
      deemed to be adenomatoid nodules, follicular adenomas and epithelial neoplasms
      showed no immunoreactivity for HBME1 and CK19 and, of these, only a single AN
      showed immunoreactivity for p63. Cases deemed to be FVPCs showed diffuse
      immunoreactivity for HBME1 and CK19 and 1 reacted with antibodies to p63. Of
      control PCs and other thyroid lesions, reactivity for HBME1, CK19, and p63 was
      observed in 8/8, 7/7, and 7/8 and 3/27, 7/27, and 7/27 cases, respectively.
      CONCLUSIONS: A sclerotic or hyalinized stroma with a trabecular growth pattern
      may be seen in a number of different thyroid lesions and, when seen, is usually a
      focal feature of a lesion other than HTA. Immunohistochemistry may be of
      assistance as cases of FVPC with prominent hyalinization and trabeculation will
      show immunoreactivity for HBME1 and CK19, whereas HTAs and other thyroid lesions
      with hyalinization and trabeculation will not.

PMID- 17001159
TI  - Gastrointestinal involvement in mantle cell lymphoma: a prospective clinic,
      endoscopic, and pathologic study.
AB  - The frequency of gastrointestinal (GI) tract involvement in mantle cell lymphoma
      (MCL) at diagnosis is reported to be below 30%. To investigate the actual
      frequency of GI involvement by MCL, upper and lower endoscopy was prospectively
      performed on 13 untreated MCL patients at diagnosis. Multiple biopsies from
      endoscopically normal and abnormal gastric and colonic mucosa were studied with
      immunohistochemistry (IHC) for CD20, CD5, and cyclin D1, as well as fluorescence
      in situ hybridization (FISH) for t(11;14) and polymerase chain reaction (PCR) for
      immunoglobulin heavy chain gene. Abnormal mucosa was identified in 38% of cases
      by upper endoscopy (mainly mild nonspecific gastritis) and in 54% of cases by
      lower endoscopy (mostly micropolyps). Histologically, infiltration by MCL was
      demonstrated in the stomach in 77% of cases and in the colon in 77% of cases. As
      a whole, 92% of patients showed upper or lower GI tract infiltration by MCL.
      Histologic evidence of MCL involvement was present in all cases with
      endoscopically abnormal mucosa, but it was also observed in two-thirds of cases
      with endoscopically unremarkable mucosa. Positive cyclin D1 IHC was seen in all
      instances displaying CD20 and CD5-positive lymphoid infiltrates, whereas t(11;14)
      was demonstrated by FISH in 63.5% and PCR was clonal in 64% of those instances.
      In conclusion, the great majority of MCL patients showed GI tract involvement at
      the time of diagnosis, not uncommonly in the form of minute lymphoid infiltrates.
      IHC for cyclin D1 was significantly more sensitive than FISH t(11;14) or PCR for
      immunoglobulin heavy chain gene to confirm MCL in this setting.

PMID- 17001160
TI  - A working group classification of focal prostate atrophy lesions.
AB  - Focal atrophy is extremely common in prostate specimens. Although there are
      distinct histologic variants, the terminology is currently nonstandardized and no
      formal classification has been tested for interobserver reliability. This lack of
      standardization hampers the ability to study the biologic and clinical
      significance of these lesions. After informal and formal meetings by a number of
      the authors, focal atrophy lesions were categorized into 4 distinct subtypes as
      follows: (i) simple atrophy, (ii) simple atrophy with cyst formation, (iii)
      postatrophic hyperplasia, and (iv) partial atrophy. In phase 1 of the study,
      pathologists with varying levels of experience in prostate pathology were invited
      to view via the Internet a set of "training" images with associated descriptions
      of lesions considered typical of each subtype. In phase 2 of the study, each
      participant provided diagnoses on a series of 140 distinct "test" images that
      were viewed over the Internet. These test images consisted of the 4 subtypes of
      atrophy and images of normal epithelium, high grade prostatic intraepithelial
      neoplasia, and carcinoma. The diagnoses for each image from each pathologist were
      compared with a set of "standard" diagnoses and the kappa statistic was computed.
      Thirty-four pathologists completed both phases of the study. The interobserver
      reliability (median kappa) for classification of lesions as normal, cancer,
      prostatic intraepithelial neoplasia, or focal atrophy was 0.97. The median kappa
      for the classification of atrophy lesions into the 4 subtypes was 0.80. The
      median percent agreement with the standard diagnosis for the atrophy subtypes
      were: simple 60.6%, simple with cyst formation 100%; postatrophic hyperplasia
      87.5%; partial atrophy 93.9%. The lower percentage for simple atrophy reflected a
      propensity to diagnose some of these as simple atrophy with cyst formation. Seven
      pathologists completed the phase 2 analysis a second time, and their
      intraobserver reproducibility was excellent. Three of 4 pathologists with low
      agreement with the standard diagnosis for simple atrophy improved their scores
      after repeating the analysis after re-examination of the "training set" of
      images. In conclusion, these criteria for variants of focal prostate atrophy may
      facilitate studies to examine the relation between various patterns of prostate
      atrophy and prostate cancer.

PMID- 17001161
TI  - Evaluation of ERBB2 gene status and chromosome 17 anomalies in male breast
      cancer.
AB  - Male breast cancer (MBC) is an uncommon neoplasm that shares several biologic
      characteristics with its female counterpart. In the latter, abnormalities in the
      expression and/or copy number of the ERBB2 gene are present in 10% to 30% of
      invasive carcinoma and behave as poor prognostic markers. ERBB2 abnormalities
      have also been reported in MBC, yet at lower frequency, but their prognostic
      significance remains controversial. Furthermore, no study has addressed the
      impact of chromosome 17 abnormalities in MBC survival. In this study, the ERBB2
      gene status (overexpression and amplification) and chromosome 17 numerical
      abnormalities were investigated in a series of 50 archival cases of MBC. The
      results, together with patient's age, histologic grade, pathologic stage, and
      estrogen receptor status were correlated with overall survival. ERBB2-protein
      overexpression was present in 7 cases (14%), ERBB2-gene amplification in 4 (8%),
      and aneuploidy of chromosome 17 in 12 cases (33.3%). The pathologic stage, ERBB2
      overexpression and ERBB2 amplification were significantly correlated with overall
      survival (P=0.002, 0.016, and 0.009, respectively). No correlation was observed
      between chromosome 17 aneuploidy and overall survival. Therefore, despite their
      low incidence in MBC, expression abnormalities of ERBB2 behave, together with the
      pathologic stage of the tumor, as predictors of overall survival, akin to what
      has been reported for its female counterpart.

PMID- 17001162
TI  - Sarcomatoid basal cell carcinoma--predilection for osteosarcomatous
      differentiation: a series of 11 cases.
AB  - Primary cutaneous carcinomas rarely show heterologous malignant mesenchymal
      differentiation. We report 11 cases of sarcomatoid basal cell carcinoma (BCC)
      with osteosarcomatous differentiation. The patients (7 men and 4 women) ranged in
      age from 61 to 92 years (median 75 y). The tumors presented as exophytic nodules
      (0.3 to 7 cm) on the head (n=6), upper limb (n=3), and lower limb (n=2). All
      lesions were completely excised. Seven patients were alive without evidence of
      disease (follow-up interval 5 to 24 mo) and 1 patient died of unrelated causes at
      7 months without evidence of disease. On histology, the tumors were dermal in
      location with 2 cases showing focal subcutaneous involvement. Ten tumors were
      well-circumscribed and 1 tumor showed focally infiltrative edges. Ten tumors
      revealed conventional BCC associated with varying proportions of osteosarcomatous
      and undifferentiated sarcomatous stroma. Transition from neoplastic epithelial to
      mesenchymal cells was seen in 8 cases. One case showed a purely osteoclastic
      giant cell rich malignant mesenchyme, interpreted as representing early stages of
      osteosarcomatous transformation. Previously unreported in sarcomatoid BCC, the
      mesenchymal component of another two cases displayed predominant malignant giant
      cell tumor like areas and 1 further case disclosed areas reminiscent of
      telangiectatic osteosarcoma. Pancytokeratins (AE1/3 and MNF116) and smooth muscle
      actin stained occasional undifferentiated sarcomatous cells in 2 and 3 tumors,
      respectively. MNF116 and EMA were focally positive in osteosarcomatous tumor
      cells of 1 case. Although the follow-up interval is short, our data suggest an
      excellent prognosis for polypoid and exophytic sarcomatoid BCC after complete
      surgical resection.

PMID- 17001164
TI  - Sarcomatoid carcinoma of the prostate: a study of 42 cases.
AB  - Sarcomatoid carcinoma of the prostate is a rare type of prostatic cancer. With
      the exception of 1 study, the morphologic features and patient outcomes have been
      reported only in relatively small case series and individual reports. We examined
      transurethral resection, needle biopsy, and radical prostatectomy specimens from
      42 patients with sarcomatoid carcinoma of the prostate, all of which were
      received in consultation. Clinical information on 32 patients was obtainable.
      Five patients were lost to follow-up and information on the 5 remaining patients
      could not be obtained. Prior prostatic adenocarcinoma: The majority of patients
      (n=21; 66%) had a prior history of acinar adenocarcinoma of the prostate. Of the
      14 men with available data, reported Gleason scores were 6 (n=7), 8 (n=4), and 10
      (n=3). Of the remaining patients for whom this information was known, 11 patients
      presented with de novo sarcomatoid carcinoma. The time between the original
      diagnosis of acinar adenocarcinoma and diagnosis of sarcomatoid carcinoma ranged
      from 6 months to 16 years (mean 6.8 y). Concurrent adenocarcinoma: The majority
      of patients demonstrated a concurrent high grade acinar carcinoma of Gleason
      score 7 (n=3), 8 (n=9), 9 (n=10), and 10 (n=10). A subset of patients contained
      an admixed ductal adenocarcinoma (n=4), small cell carcinoma (n=3), squamous cell
      carcinoma (n=3), or other unusual pattern of prostate carcinoma (n=3). In 1 case,
      the diagnosis was based on immunohistochemical evidence of epithelial
      differentiation along with the history of prior adenocarcinoma. Morphology of the
      sarcomatoid component: The percentage of sarcomatoid growth ranged from 5% to 99%
      (mean 65%). Bizarre atypia with giant cells was present in 55% of cases. Admixed
      heterologous elements were identified in 10 cases (29%), including
      osteosarcomatous (n=7), chondrosarcomatous (n=5), and rhabdomyosarcomatous (n=2)
      elements. Of the 12 cases with received immunostains of the sarcomatoid
      component, 5/7 cases were at least focally positive for cytokeratin, 1/1 case was
      focally positive for Cam5.2, and 3/6 cases were focally positive for prostate
      acid phosphatase. The sarcomatoid component did not demonstrate immunoreactivity
      for prostate-specific antigen in 8 cases. PROGNOSIS: approximately half of all
      patients developed metastatic disease either at time of presentation or
      subsequently. Of patients with meaningful follow-up, 6/7 died within 1 year of
      the diagnosis of sarcomatoid carcinoma; 20 were alive yet with very short follow
      up (median 1 y; mean 2.3 y). Kaplan-Meier analysis revealed that the actuarial
      risk of death at 1 year after diagnosis of sarcomatoid carcinoma was 20%. No
      correlation was identified between patient survival and morphologic features,
      before radiation or hormone therapy, or concurrent high-grade prostate cancer.
      Sarcomatoid carcinoma demonstrates diverse spindle and epithelial cell
      morphologies. The sarcomatoid component often has heterologous elements and, in 1
      case, no epithelial component was seen on hematoxylin and eosin-stained sections.
      The epithelial component is typically high-grade acinar adenocarcinoma, yet other
      aggressive tumor subtypes such as ductal adenocarcinoma and small cell carcinoma
      may also be seen. Sarcomatoid carcinoma is an aggressive form of prostate cancer,
      the prognosis of which is dismal regardless of other histologic or clinical
      findings.

PMID- 17001163
TI  - Epidermal growth factor receptor mutation in lung cancer are linked to
      bronchioloalveolar differentiation.
AB  - In lung cancer, an association was made between drastic clinical response to
      epidermal growth factor receptor (EGFR) inhibitors and the presence of somatic
      mutations within the tyrosine kinase domain of the EGFR. In some cases, patients
      with partial response or disease stabilization do not always have EGFR-mutated
      tumors. To go further in the characterization of the EGF pathway, we screened
      EGFR, ERBB2, ERBB3, KRAS, BRAF, and PIK3CA for mutations in 2 groups of White
      patients with nonsmall cell lung cancer (45 cancers from women and 46 cancers
      from men). Associations between TP53 mutations, clinicopathologic parameters, and
      EGF pathway molecular alterations were analyzed. All mutations were exclusive and
      essentially found in EGFR and KRAS. We demonstrated that EGFR mutations were
      linked to female sex, absence of smoking, late age at diagnosis, and
      adenocarcinoma (ADC) with bronchioloalveolar (BAC) features. Moreover, in
      invasive ADC with BAC component, microdissection assays showed that mutations
      were retrieved in both tumor subtypes suggesting that EGFR mutations appear early
      in lung carcinogenesis. On the contrary, KRAS mutations correlated with smoking,
      younger age at diagnosis, and ADC subtype regardless of BAC differentiation.
      These results suggest the existence of distinct carcinogenesis pathways both
      leading to disruption of EGF regulation and targeted either by tobacco
      carcinogens or by unidentified toxic. The identification of BAC features in ADC
      helps clustering patients that are more likely to fit the EGFR-mutated group.

PMID- 17001165
TI  - Alveolar soft-part sarcoma of the urinary bladder with urethral recurrence: a
      unique case with emphasis on differential diagnoses and diagnostic utility of an
      immunohistochemical panel including TFE3.
AB  - Alveolar soft-part sarcoma (ASPS) is a rare, clinically, morphologically,
      ultrastructurally, and cytogenetically distinctive malignant mesenchymal tumor
      that most classically occurs in the extremities of adolescents and young adults,
      but has also been described in a number of unusual sites. The molecular signature
      of ASPS is a specific der(17)t(X;17)(p11.2;q25) translocation, which results in
      the fusion of TFE3 transcription factor gene (from Xp11) with ASPL at 17q25. The
      ASPL-TFE3 fusion protein encoded by the fusion transcript can be detected
      immunohistochemically with commercially available antibodies to the carboxy
      terminus of TFE3. Herein, we report a unique case of ASPS presenting in the
      bladder with subsequent urethral recurrence in a 25-year-old woman. We emphasize
      the differential diagnoses engendered by ASPS including common, not-so-common,
      and rare tumors involving the urinary bladder that have a nested architecture,
      and both clear and eosinophilic cytoplasm, and demonstrate the utility of a broad
      immunohistochemistry panel including TFE3 for diagnosis.

PMID- 17001166
TI  - Formation of the 12q14-q15 amplicon precedes the development of a well
      differentiated liposarcoma arising from a nonchondroid pulmonary hamartoma.
AB  - Pulmonary hamartoma is a benign neoplasm that rarely recurs or undergoes
      malignant transformation. Herein, we report a 48-year-old woman with a history of
      an incomplete excised nonchondroid pulmonary hamartoma presenting as an indolent
      tumor recurrence. Excision of the tumor revealed a well-differentiated
      liposarcoma arising from the hamartomatous component. Fluorescence in situ
      hybridation analysis for HMGA2 and MDM2 was performed on both hamartomatous and
      liposarcomatous component. MDM2 and HMGA2 amplification were found in a subset of
      stromal cells in the hamartomatous component and in most cells of the well
      differentiated liposarcoma. No rearrangement HMGA2 was found in the pulmonary
      hamartoma component. These findings suggest that the formation of the 12q14-q15
      chromosome amplicon, the characteristic cytogenetic finding of well
      differentiated liposarcomas and the structural genomic component of the
      supernumerary ring and giant rod chromosomes, occurred before the morphologic
      changes characteristic of these malignant adipose tissue tumors and likely
      represents a very early molecular event in their development.

PMID- 17001167
TI  - Diabetic (lymphocytic) mastopathy with exuberant lymphohistiocytic and
      granulomatous response: a case report with review of the literature.
AB  - We report a case of a 66-year-old woman who presented with multiple painless
      masses in both breasts. Prior bilateral biopsies were diagnosed as Rosai-Dorfman
      disease (Sinus Histiocytosis with Massive Lymphadenopathy). A recent lumpectomy
      specimen revealed a gray-white smooth cut surface with a discrete masslike
      lesion. The histopathology demonstrated a fibrotic breast parenchyma with foci of
      dense fibrosis and scattered inconspicuous breast epithelium surrounded by
      lymphocytes that formed aggregates and follicles with germinal centers. The
      inflammation was in a periductal, perilobular, and perivascular distribution. In
      addition, an exuberant inflammatory response with histiocytes and fibroblasts was
      present. This inflammatory response focally surrounded areas of fat necrosis and
      formed noncaseating granulomas with rare multinucleated giant cells. This process
      had infiltrative, ill-defined edges and involved the subcutaneous tissues. The
      overlying epidermis was normal. The final diagnosis was diabetic mastopathy with
      an exuberant lymphohistiocytic response. The differential diagnosis included
      Rosai-Dorfman disease, inflammatory myofibroblastic tumor, granulomatous
      mastitis, sclerosing lipogranulomatous response/sclerosing lipogranuloma, lupus
      panniculitis, and rheumatoid nodules. Immunohistochemical studies and flow
      cytometry confirmed the polyclonal nature of the lymphoid infiltrate. After the
      histologic evaluation, we inquired if the patient had a history of diabetes
      mellitus, and learned that she did have type 2 noninsulin-dependent diabetes
      mellitus. In conclusion, we report a case of diabetic mastopathy that presents
      with bilateral tumorlike masses and an unusual exuberant lymphohistiocytic
      response with granuloma formation. The pathologist may not be provided with a
      history of diabetes mellitus, but the characteristic fibrosis, lymphocytic
      ductitis/lobulitis, and sclerosing lobulitis with perilobular and perivascular
      lymphocytic infiltrates should provide clues for an accurate diagnosis, even when
      an exuberant and an unusual lymphohistiocytic response is present. A timely
      accurate diagnosis can help limit repeat surgeries in this vulnerable group of
      patients.

PMID- 17001168
TI  - Perineurioma versus fibroblastic polyp of the colon.

PMID- 17001169
TI  - Cytokeratin 14 is not a specific marker for renal oncocytomas.

PMID- 17001170
TI  - Anaplastic nephrogenic rest.

PMID- 17001171
TI  - A new familial GIST identified.

PMID- 17001172
TI  - New approaches to primary brain tumor treatment.
AB  - Primary brain tumors represent over 100 different tumor types with widely
      divergent biologies and clinical outcomes, but these neoplasms frequently pose
      similar challenges to neuro-oncologists. Malignant gliomas are the most common
      type of primary intrinsic brain tumor in adults and remain extremely lethal.
      Current standard-of-care therapies for these cancers include surgery, radiation
      and palliative cytotoxics, which have significant side-effects and limited
      efficacy. Advances in our understanding of the molecular underpinnings of cancer
      have led to targeted molecular therapies that may permit improvement in
      therapeutic efficacy and reduced toxicity; these therapies, however, still face
      many challenges. Signal transduction pathways that are inappropriately regulated
      in brain cancers include growth factors and their receptors (e.g. epidermal
      growth factor receptor, vascular endothelial growth factor receptor and platelet
      derived growth factor receptor), which regulate cellular interactions with the
      microenvironment and intracellular oncogenic pathways. Low-molecular-weight
      inhibitors have been developed to target many kinases and may have advantages in
      terms of delivery. Monoclonal antibodies may have greater specificity, but face
      delivery restrictions. Preferential tumor delivery of chemotherapies, conjugated
      toxins and radioisotopes has been achieved through convection-enhanced delivery,
      intratumoral implants and intra-arterial infusion. Despite these advances, few
      molecularly targeted therapies have demonstrated significant antineoplastic
      activity for a broad range of patients, possibly due to tumor and patient
      heterogeneity. Improved functional neuropathology and imaging may permit
      identification of patient subgroups for which clinical responses may be enriched.
      It is probable, however, that targeted therapies will be most effective in
      combination either with one another or with cytotoxic therapies. In this study,
      we review the current state of new therapies for malignant gliomas.

PMID- 17001173
TI  - Cyclopentenone: a special moiety for anticancer drug design.
AB  - The conjugate cyclopent-en-one chemical group is a special moiety for anticancer
      drugs. Studies on cyclopentenone prostaglandins, clavulones and other compounds
      have revealed its mechanism of action and a wide spectrum of intracellular
      targets, ranging from nuclear factors to mitochondria. The introduction of the
      cyclopentenone moiety into molecules, such as jasmonates and chalcones, has been
      shown to boost their anticancer potential. In this work, reviewing pertinent up
      to-date literature, we have pointed out potentially effective cyclopentenone
      bearing compounds for anticancer clinical research and inspiring relationships
      for future drug design. In particular, it appears that the addition of
      cyclopentenone groups to target-orienting molecules, in order to inactivate
      specific proteins in cells, could be a helpful general strategy for the
      development of novel therapeutic molecules.

PMID- 17001174
TI  - Why there will never be an alternative cancer cure.

PMID- 17001175
TI  - In-vitro toxicity of Ukrain against human Ewing tumor cell lines.
AB  - Ukrain is advertised by the manufacturer as a drug for alternative cancer cures
      with high activity against progressive Ewing tumors. Using the MTT assay, we
      compared the cytotoxicity of Ukrain with the cytotoxicity of N,N',N''
      triethylenethiophosphoramide (thioTEPA), Chelidonium majus L. alkaloids,
      doxorubicin, cyclophosphamide and etoposide against four human Ewing tumor cell
      lines. In addition, we studied the cytotoxicity of thioTEPA combined with C.
      majus L. alkaloids after 48, 72 and 96 h. All compounds reduced the growth of
      Ewing tumor cell lines in a dose-dependent manner. The concentrations that
      reduced cell growth by 50% ranged between 6.2 and 31.1 micromol/l for Ukrain, 1.9
      and 26.1 micromol/l for C. majus L. extract, and 1.7 and 448 micromol/l for
      thioTEPA. The sensitivity profile of Ukrain was comparable to that of the C.
      majus L. alkaloids, and different from that of thioTEPA, cyclophosphamide,
      etoposide and doxorubicin. Overall, doxorubicin was the most cytotoxic drug
      followed by cyclophosphamide. Ukrain and the C. majus L. alkaloids were slightly
      more cytotoxic than etoposide, while thioTEPA showed the lowest cytotoxicity. Co
      exposure of thioTEPA with C. majus L. alkaloids resulted in additive but not in
      synergistic cytotoxicity. The in-vitro results indicate that the cytotoxicity of
      Ukrain against Ewing tumors is comparable to that of etoposide. While the latter
      can be used on the basis of broad clinical experience and known risk-benefit
      ratio, Ukrain for the present might be considered as a candidate for subsequent
      drug development by xenograft studies followed by systematic clinical trials.

PMID- 17001176
TI  - Antisense-mediated melanoma inhibitor of apoptosis protein downregulation
      sensitizes G361 melanoma cells to cisplatin.
AB  - Malignant melanoma is an aggressive form of skin cancer that is highly resistant
      to conventional therapies. The melanoma inhibitor of apoptosis protein is a
      potent inhibitor of apoptosis and is overexpressed in melanoma cells, but
      undetectable in most normal tissues including melanocytes. We designed 20-mer
      phosphorothioate antisense oligonucleotides complementary to five putatively
      single-stranded sites on the melanoma inhibitor of apoptosis protein mRNA and
      investigated their ability to sensitize G361 melanoma cells to cisplatin.
      Inhibition of melanoma inhibitor of apoptosis protein mRNA and protein expression
      were measured by real-time polymerase chain reaction and immunoblotting. Cell
      viability and apoptosis were quantitated by colorimetric viability assays and by
      annexin V staining, respectively. Oligonucleotide M706 was identified as the most
      efficient antisense sequence which downregulated melanoma inhibitor of apoptosis
      protein mRNA and protein levels in G361 cells by 68 and 78%, respectively. The
      specificity of target downregulation was confirmed using scrambled sequence
      control oligonucleotides that only marginally decreased melanoma inhibitor of
      apoptosis protein expression. Whereas downregulation of melanoma inhibitor of
      apoptosis protein moderately inhibited cell growth by 26%, in combination with
      cisplatin, this resulted in a supra-additive effect with almost 57% reduction in
      G361 cell viability compared with cisplatin alone (17%) (P<0.05). Cell death was
      mainly due to apoptosis as demonstrated by a 3- to 4-fold increase in annexin V
      positive cells and typical morphological changes compared with controls. In
      summary, we describe a new antisense oligonucleotide that efficiently
      downregulates melanoma inhibitor of apoptosis protein expression and sensitizes
      melanoma cells to cisplatin.

PMID- 17001177
TI  - Anticancer drugs induce mdr1 gene expression in recurrent ovarian cancer.
AB  - Ovarian cancer is currently the most lethal gynecologic malignancy in Europe and
      the US. Platin analogues and paclitaxel demonstrate high remission rates, but
      unfortunately the efficacy of cytostatic agents is limited by the development of
      multidrug resistance (mdr). Clinical paclitaxel resistance is often associated
      with mdr1 overexpression. In a recent study, we introduced a highly specific
      quantitative real-time reverse transcriptase polymerase chain reaction for the
      quantification of mdr1 transcripts. In the present study, we demonstrate that
      primary tumor cells from patients with recurrent ovarian cancer overexpress mdr1.
      To evaluate mdr1 expression, we collected tumor cells from 77 ovarian cancer
      patients (13 chemotherapy-naive ovarian cancer, 64 recurrent ovarian cancer).
      Cancer cells were aspirated from 49 solid specimens (63%) and 28 ascitic fluids
      (37%). Subsequently, cancer cells were exposed in 221 short-term cultures either
      to blank medium (control) or to a single anticancer drug, cisplatin, doxorubicin
      or paclitaxel. The drug concentrations applied referred to clinical relevant
      doses. mdr1 mRNA expression was significantly higher in specimens from recurrent
      ovarian cancer incubated in paclitaxel than in specimens from chemotherapy-naive
      ovarian cancer. No significant differences were detectable between the mean value
      of mdr1 mRNA expression in tumor specimens from recurrent ovarian cancer
      incubated in cisplatin or doxorubicin. Differences within the untreated patients
      group were also not statistically significant. The result of this study confirms
      clinical observations, as well as in-vitro studies based on tumor cell lines,
      that paclitaxel resistance is correlated with mdr1 overexpression.

PMID- 17001178
TI  - RP101 improves the efficacy of chemotherapy in pancreas carcinoma cell lines and
      pancreatic cancer patients.
AB  - RP101 [(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU)], which supports apoptosis and
      prevents the acquisition of chemoresistance, was tested in cultured human
      pancreatic tumor cells. RP101 downregulated uridine phosphorylase, a marker of
      poor prognosis, and APEX1, which is involved in DNA repair, and repressed Stat3
      and its target vascular endothelial growth factor. Furthermore, RP101 activated
      antitumor immunity as demonstrated by enhanced cytolytic activity of NK-92
      natural killer cells. This was concomitant with an enhanced expression of
      lymphotoxins alpha and beta, natural killer cell transcript 4, tumor necrosis
      factor LIGHT/TNFSF-14, and intercellular adhesion molecule-1 in pancreas
      carcinoma cells. These results encouraged us to investigate the effect of RP101
      in pancreas cancer patients. Here, we present data from two RP101 combination
      therapy schemes. In a first pilot study, 13 patients in stage III and VI of the
      disease were treated with gemcitabine +cisplatin+RP101. RP101 co-treatment
      enhanced remissions, survival and time to progression. Seventy-seven percent of
      the patients lived or have lived longer than 1 year, and 23% have lived more than
      2 years. Median survival was 447 days, time to progression 280 days and the
      response rate 33%. A second study with 21 patients in similar stages of disease,
      treated with RP101+gemcitabine alone, confirmed the results of the pilot study.
      Eighty-three percent of the presently evaluable patients live or lived 0.5 years
      or longer and 33% 1 year or longer. Considering both studies, the tumor control
      was 94%. The data indicate that acquisition of chemoresistance was prevented and
      the antitumor efficacy of standard chemotherapy was improved. To our knowledge,
      RP101 co-treatment is more efficient than any other regimen published.

PMID- 17001179
TI  - Feasibility and usefulness of high-dose chemotherapy (high-dose ifosfamide,
      carboplatin and etoposide) combined with peripheral blood stem cell
      transplantation for male germ cell tumor: a single-institute experience.
AB  - Although the usefulness of high-dose chemotherapy with peripheral blood stem cell
      transplantation for advanced germ cell tumor is still under evaluation in phase
      III randomized controlled studies, this approach is currently used as one
      treatment option for relapsed or advanced male germ cell tumor. Clinical outcomes
      of high-dose chemotherapy for a single institute from Japan are presented herein.
      We administered 63 courses of high-dose ifosfamide, carboplatin and etoposide
      chemotherapy (1250 mg/m carboplatin; 1500 mg/m etoposide; 7.5 g/m ifosfamide) to
      34 men with germ cell tumors. Of these, 27 patients underwent high-dose
      ifosfamide, carboplatin and etoposide as first-line therapy after 2-3 courses of
      conventional bleomycin, etoposide and cisplatin chemotherapy, and seven patients
      underwent high-dose ifosfamide, carboplatin and etoposide for relapsed germ cell
      tumor. Peripheral blood stem cells were harvested during previous chemotherapy
      and sufficient CD34 cells were harvested for transplantation. Although all
      patients experienced grade 4 hemotoxicity, leukocyte counts recovered to above
      1000/mul within 8-11 days after peripheral blood stem cell transplantation. No
      treatment-related deaths occurred. After a mean follow-up of 45 months (range 12
      118 months), 23 of 34 patients (67.6%) remained disease-free. High-dose
      ifosfamide, carboplatin and etoposide could be performed safely, and could offer
      an effective means of treating advanced or refractory germ cell tumors in men.

PMID- 17001180
TI  - A phase II study of an oxaliplatin/vinorelbine/5-fluorouracil combination in
      patients with anthracycline-pretreated and taxane-pretreated metastatic breast
      cancer.
AB  - The aim of this phase II study was to evaluate safety and efficacy of an
      oxaliplatin/vinorelbine/5-fluorouracil (FON) combination in anthracycline and
      taxane-pretreated metastatic breast cancer patients. The following treatment was
      given: on day 1 of a 21-day cycle, oxaliplatin 130 mg/m (2-h intravenous
      infusion); on days 1 and 5, vinorelbine [dose level (DL) 1: 17.5 mg/m; DL2: 22
      mg/m]; on days 1-5, continuous infusion 5-fluorouracil (DL1: 600 mg/m/day; DL2:
      750 mg/m/day). Forty-seven patients were treated (DL1: 43; DL2: 4). Median age
      was 54 years; 68% had liver metastases, 53% were taxane refractory/resistant and
      38% were anthracycline refractory/resistant. Patients received a median of six
      treatment cycles. Of 46 eligible patients, 16 had partial response; the overall
      response rate was 34.8% (95% confidence interval 21.3-50.3%), 11 had stable
      disease lasting more than 4 months. Median follow-up was 13.0 months, median time
      to progression 5.7 months and estimated overall survival 18.8 months. DL2 was too
      toxic with three patients having grade 3-4 toxicity, including one death. At DL1,
      26 patients (60%) experienced grade 3-4 neutropenia (six febrile neutropenia) and
      eight had grade 3 oxaliplatin-specific peripheral neuropathy after a median of
      646.4 mg/m oxaliplatin (range 124-1619 mg/m). Oxaliplatin (130 mg/m, day
      1)/vinorelbine (17.5 mg/m, days 1,5)/5-fluorouracil (600 mg/m/day, days 1-5)
      demonstrate encouraging activity and a manageable safety profile in anthracycline
      and taxane-pretreated metastatic breast cancer patients.

PMID- 17001181
TI  - Dose-escalated abarelix in androgen-independent prostate cancer: a phase I study.
AB  - Follicle-stimulating hormone has been shown to be a mitogen in preclinical models
      of androgen-independent prostate cancer and abarelix has been previously shown to
      significantly reduce follicle-stimulating hormone levels in patients when
      administered monthly. Consequently, we evaluated the safety of more frequent
      (biweekly) dosing of abarelix and characterized the effect of this dosing
      schedule on serum follicle-stimulating hormone levels in men with prostate cancer
      that is progressing despite luteinizing hormone-releasing hormone agonist
      therapy. Twenty-one patients with prostate cancer progressing on gonadotropin
      releasing hormone agonist therapy discontinued the gonadotropin-releasing hormone
      agonist and received abarelix-depot 100 mg by intramuscular injection every 2
      weeks for up to 12 weeks. Safety profile and effect on serum follicle-stimulating
      hormone were the primary end-points, while prostate-specific antigen response was
      a secondary end-point. Abarelix therapy was generally well tolerated. One patient
      experienced an acute immediate allergic reaction. The mean follicle-stimulating
      hormone serum concentration declined from 3.5 mIU/ml (95% confidence interval:
      2.7-4.3) to 2.0 mIU/ml (95% confidence interval: 1.3-2.6) on day 57 and to 2.0
      mIU/ml (95% confidence interval: 0.9-3.0) on day 85 (P=0.008 in a Kruskal-Wallis
      test), but no patient's follicle-stimulating hormone has reached the lower limit
      of quantitation (below 0.15 mIU/ml). No patient met criteria for prostate
      specific antigen response. At the end of 12 weeks of therapy, three (14.3%)
      patients had no change in prostate-specific antigen levels on days 57 and 85
      compared with baseline. Twelve patients (57%) had stable disease throughout
      treatment defined as percent change from baseline within -50 to 50% at a given
      time-point confirmed by a second measurement at least 4 weeks later. Treatment
      with biweekly abarelix in patients with androgen-independent prostate cancer is
      feasible with no unexpected toxicity, but fails to completely suppress serum
      follicle-stimulating hormone levels or produce prostate-specific antigen
      responses.

PMID- 17001182
TI  - Alternating intravenous and oral vinorelbine plus epirubicin with pegfilgrastim
      as neoadjuvant treatment of locally advanced breast cancer.
AB  - In order to downstage locally advanced breast cancer, neoadjuvant chemotherapy
      consisting of intravenous vinorelbine 25 mg/m plus epirubicin 75 mg/m given on
      day 1 and oral vinorelbine 60 mg/m on day 8 was administered every 3 weeks for
      four courses. On day 2, all patients received a single subcutaneous injection of
      pegfilgrastim (6 mg). From March 2004 to June 2005, 22 patients were enrolled.
      Patients characteristics were: median age, 53 years (range: 39-70 years);
      postmenopausal, 7/22; clinical TNM stage, T2 (n=14), T3 (n=8), N0 (n=17) and N1
      (n=5). The median number of courses was four (range: two to six courses) with
      full dose intensity. National Cancer Institute grade 3 haematological toxicities
      observed were neutropenia in 9% of patients, anaemia in 13% of patients and
      thrombocytopenia in 9% of patients; no toxicity grade 4 occurred. Two patients
      (9%) registered grade 2 polyneuropathy; no cardiac failure was observed.
      Conservative surgery was performed in 14 patients (63%). All patients were
      evaluable for response: complete pathological response was documented in three
      patients (13.6%); three patients (13.6%) obtained more than 75% of tumour size
      reduction; 11 other patients (50%) had 50% of tumour size reduction; stable
      disease was observed in five patients (22.7%). The present findings indicate that
      vinorelbine in combination with epirubicin is an effective and safe treatment in
      locally advanced breast cancer: this regimen obtained more than 50% of tumour
      size reduction in 77% of patients; the use of pegfilgrastim allowed full dose
      intensity. Oral vinorelbine on day 8 offers greater convenience to the patient by
      reducing the need for intravenous injection and the time spent in hospital.

PMID- 17001183
TI  - Etoposide pharmacokinetics in children treated for acute myeloid leukemia.
AB  - We studied the pharmacokinetics of etoposide in 45 children treated for newly
      diagnosed acute myeloid leukemia. Etoposide, 100 mg/m body surface area/24 h, was
      administered by 96-h continuous intravenous infusion. Concomitantly, the children
      received cytarabine 200 mg/m/24 h by intravenous infusion and 6-thioguanine 100
      mg/m twice daily orally. Median total body clearance in children 0.5-1.8 (n=4)
      and 2.3-17.7 years old (n=36) without Down's syndrome was 17.1 and 17.6 ml/min/m,
      respectively (P=0.96). Five children with Down's syndrome had a median clearance
      of 13.6 ml/min/m (P=0.067 compared with non-Down's syndrome children). Eighteen
      of the children received a second identical treatment course 3-4 weeks later;
      there was a significant correlation between individual clearance values
      (rho=0.56; P=0.017). We found no significant correlation between etoposide
      pharmacokinetics and the remission rate or the relapse rate. In conclusion, our
      findings indicate that special dose-calculation guidelines for infants above 3
      months old are not substantiated by age-dependent pharmacokinetics of etoposide.
      Down's syndrome children might be candidates for dose reduction if our data are
      confirmed in larger numbers of patients. Low course-to-course variability
      indicates that pharmacokinetically guided dosing of etoposide might be clinically
      relevant, if larger studies can demonstrate that this approach decreases toxicity
      or increases response rates.

PMID- 17001184
TI  - Peripheral neuropathy exacerbation associated with topical 5-fluorouracil.
AB  - Peripheral neuropathy secondary to 5-flourouracil and capecitabine (Xeloda) has
      been reported. We report the first case of exacerbation of peripheral neuropathy
      related to topical 5-flourouracil (Efudex). A 70-year-old Caucasian male with a
      history of actinic keratosis for 15 years was treated intermittently with topical
      application of 5-flourouracil. He also developed sensory peripheral neuropathy
      around the same time, but extensive work-up disclosed no clear etiology. In early
      2005, he developed an exacerbation of his peripheral neuropathy following a 21
      day course of topical 5-flourouracil for actinic keratosis, especially pain and
      parasthesias. Dihydropyrimidine dehydrogenase activity was evaluated in the
      peripheral mononuclear cells both by radioassay and by [2-C] uracil breath test.
      Dihydropyrimidine dehydrogenase activity was within the normal range by both
      methods. Stopping topical 5-flourouracil resolved the symptoms to baseline.
      Instead of topical 5-flourouracil, topical imiquimod was used which did not
      exacerbate his neuropathy. He was not re-challenged with topical 5-flourouracil.
      Topical 5-flourouracil has been known to cause mainly dermatological adverse
      effects, but systemic effects because of absorption are possible, especially in
      dihydropyrimidine dehydrogenase-deficient patients. As our patient had no other
      cause responsible for his neuropathy, the onset of symptoms coincided
      historically with topical application of 5-flourouracil and the 5-flourouracil
      usage preceded an exacerbation of sensory symptoms, we conclude that this drug
      was responsible for his polyneuropathy.

PMID- 17001185
TI  - Once-daily intravenous busulfan in children prior to stem cell transplantation:
      study of pharmacokinetics and early clinical outcomes.
AB  - We studied the pharmacokinetics and clinical outcome of a new once-daily
      intravenous area under the curve-targeted dosing scheme for busulfan based on
      body surface area. Eighteen children undergoing busulfan-based conditioning for
      allogeneic stem cell transplantation were enrolled. The age of the children
      ranged from 0.5 to 16 years. For all children, the starting dose was 80 mg/m.
      Unlimited dose adjustment was allowed to reach the target area under the curve
      (3800 micromol/l . min). This target area under the curve was determined on the
      basis of a previous study in our hospital. Pharmacokinetic studies were performed
      after the first dose. The median area under the curve on day 1 was 2616 (range
      1781-5040) micromol/l . min at a dose of 80 mg/m. This resulted in a median dose
      increment to 114 (range 62-168) mg/m to reach the target area under the curve. In
      only one patient, the dose was decreased. Donor engraftment was established in 14
      out of 18 patients (78%). Two of the four patients were successfully
      retransplanted. Relapse occurred in two patients (one died, one received
      additional treatment). Fourteen patients survived with a median follow-up of 1.6
      years (1.0-2.2 years). The disease-free survival was 66% (12 of 18 patients).
      Despite the high systemic peak levels, there was no new unexpected or unusual
      toxicity. Moderate veno-occlusive disease was seen in one patient only. We
      conclude that intravenous busulfan in children administered once daily is safe,
      convenient and feasible, and can be dosed surface-based, independent of age.
      There was very limited (liver) toxicity, but the rejection rate was relative
      high, which can be probably overcome by a higher exposure to busulfan. Future
      investigations should be aimed at further optimizing the target area under the
      curve of intravenous busulfan for specific patient groups.

PMID- 17001187
TI  - Concentrations of mitomycin C in rabbit corneal tissue and aqueous humor after
      topical administration.
AB  - PURPOSE: To study the aqueous and corneal pharmacokinetics of mitomycin C (MMC)
      after single topical administration to the central cornea and to evaluate the
      effects of different concentrations and different application times on the
      aqueous concentration of MMC. METHODS: Mechanical epithelium debridement of the
      central 7.5 mm of the cornea was performed in New Zealand white rabbits, and a
      sponge soaked in 0.02% MMC solution was placed on the denuded corneal stroma for
      2 minutes. Aqueous fluid and central corneal tissues samples were taken at 0.5,
      1, 2, and 3 hours thereafter. MMC concentration of the samples was analyzed by
      high-performance liquid chromatography and evaluated at different exposure times
      (range: 15-120 seconds) and concentrations of applied MMC (range: 0.005%-0.04%).
      RESULTS: Peak corneal concentration was 3.728 +/- 2.547 microg/g at 30 minutes
      after topical administration. Maximum aqueous concentration was 0.380 +/- 0.038
      microg/mL at 1 hour after topical application. The aqueous concentration of MMC
      increased in a dose-dependent manner with increasing exposure time and
      application concentration. Aqueous MMC concentration increased at a higher rate
      with change of applied concentration than with exposure time. CONCLUSION: Good
      penetration of MMC through central bare cornea may be noxious to endothelial
      cells. Reducing concentration or decreasing exposure time seems a good modality
      to reduce potential MMC toxicity.

PMID- 17001188
TI  - Expression of Wnt and MMP in epithelial cells during corneal wound healing.
AB  - PURPOSE: To study the expression of Wnt during corneal wound healing and to
      understand the signaling mechanism involved. METHODS: Rat cornea was demarcated
      on the central area by 4-mm trepine, and the epithelium within this area was
      removed by scalpel. The epithelium was scraped and isolated to extract RNA. To
      determine the proliferation of corneal epithelial cells, corneoscleral rims from
      human donors were treated with dispase II for 15 minutes, and epithelial cells
      were isolated. Cells were plated on a 3T3 feeder cells layer. The proliferation
      of corneal epithelial cells was evaluated by colony-forming efficiency. RESULTS:
      Wnt 5b and 7a were rapidly induced in wounded cornea, and Wnt 7a promoted
      proliferation of corneal epithelial cells. In addition, matrix metalloproteinase
      (MMP)-12 was expressed in wounded rat corneal epithelium. Transcription of MMP-12
      was responsive to Wnt/beta-catenin signaling. Function blockade of MMP-12 delayed
      Wnt 7a-induced cell proliferation. CONCLUSION: These results indicate that Wnt
      proteins and MMP-12 regulate the proliferation of corneal epithelial cells and
      that Wnt signaling contributes to the resurfacing of defective areas during
      corneal wound healing.

PMID- 17001189
TI  - Expression of 1-cys peroxiredoxin in the corneal wound-healing process.
AB  - PURPOSE: To study the regulation by mitomycin C (MMC) of 1-cys peroxiredoxin
      (Prx) expression during the corneal wound-healing process and its induction
      pathway in cultured bovine keratocytes (BKs). METHODS: Rat corneas were excised
      at 4 hours, 12 hours, 1 day, 3 days, and 7 days after photorefractive keratectomy
      (PRK). Expression of 1-cys Prx in the corneas was examined by Northern blot and
      immunoblot analyses. Cultured BKs were exposed to 0.02% MMC for 5 minutes and
      maintained under normal culture conditions for different time periods.
      Subsequently, levels of 1-cys Prx and extracellular signal-regulated kinase
      (ERK)1/2 expression were measured by immunoblot analysis using polyclonal 1-cys
      Prx, ERK1/2, or phospho-ERK1/2 antibodies. To inhibit ERK1/2 activation, the BKs
      were pretreated with 50 micromol/mL PD98059 for 1 hour before MMC exposure and
      incubated in complete medium with or without PD98059 for 24 hours. MMC-induced
      cytotoxicity was determined by colorimetric cell-counting kit-8 assay. RESULTS:
      Increased levels of 1-cys Prx expression were seen in wounded rat corneas at 12
      hours after injury and reached the highest level between 1 and 3 days, during
      which time active proliferation occurred. Induction of 1-cys Prx expression was
      obvious in proliferating BKs stimulated by growth factors. MMC treatment in
      cultured BKs resulted in increased expression of 1-cys Prx and phospho-ERK1/2 in
      a time-dependent manner. Treatment with 50 micromol/mL PD98059 significantly
      inhibited the active ERK1/2 and 1-cys Prx expression induced by MMC, leading to
      synergistic cytotoxicity in the BKs. CONCLUSION: 1-Cys Prx may function as an
      important enzyme in cell proliferation during the postinjury corneal wound
      healing process. Furthermore, the induction of 1-cys Prx expression through the
      ERK1/2 signaling pathway may contribute to cellular defense against cytotoxic
      agents, thus playing an important role in cell survival.

PMID- 17001190
TI  - Cellular senescence as a stress response.
AB  - PURPOSE: This review discusses cellular senescence, the state in which normal
      cells do not respond to growth stimuli, and shows characteristic alterations in
      their cytologic and biochemical properties and their gene expression profiles.
      METHODS AND RESULTS: Cellular senescence is elicited by various stresses. It was
      recently shown that the stress-induced mitogen-activated protein kinase p38 has a
      pivotal role in inducing cellular senescence. This finding provided biochemical
      evidence to support the notion that cellular senescence is a kind of stress
      response. CONCLUSION: Stress responses are typically found in cells and organisms
      surviving unfavorable environmental conditions. It can be argued that cellular
      senescence is an adaptive process that maintains the cell's viability by reducing
      the energy consumed for reproduction (ie, cell division) and differentiation
      related activities.

PMID- 17001191
TI  - In vivo and in vitro inhibitory effect of amniotic extraction on
      neovascularization.
AB  - PURPOSE: To prepare amniotic extraction (AE) and to test its antiangiogenic
      effect in vivo and in vitro. METHODS: AE was prepared and diluted to 50, 100, and
      200 microg/mL concentrations. Alkali burn-induced corneal neovascularization (NV)
      was produced and topically treated with different concentrations of AE or 0.1%
      dexamethasone for 7 days. Normal saline was used as a control. Corneal NV was
      visualized by heart perfusion of Chinese ink and quantified as the percentage of
      corneal NV area to the whole corneal area. Human umbilical vein endothelial cells
      (HUVECs) were primarily cultured. The effects of AE on proliferation and tube
      formation of HUVECs were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) method and in vitro angiogenesis assay. Pigment
      epithelium-derived factor (PEDF) in AE was detected by Western blot. RESULTS:
      Relative corneal NV area in the control group was 56.6% +/- 9.9%, which was
      significantly reduced by 50 microg/mL AE (47.6% +/- 6.9%; P = 0.043) and 200
      microg/mL AE (34.3% +/- 7.8%; P < 0.001) and by 0.1% dexamethasone (21.1% +/-
      1.8%; P < 0.001). HUVEC cell proliferation was significantly decreased after
      treatment with AE at concentrations of 50 and 100 microg/mL compared with control
      (P = 0.036 and 0.001, respectively). The tube formation was significantly
      suppressed by 100 microg/mL AE (70.03% +/- 4.35%) compared with control (100% +/-
      4.84%; P = 0.002). No expression of PEDF was detected in AE. CONCLUSION: AE
      inhibits NV induced by alkali burn. This effect may be elicited at least in part
      through the inhibiting activity of blood vessel endothelial cells and is not
      associated with PEDF.

PMID- 17001192
TI  - Recurrence of lattice corneal dystrophy caused by incomplete removal of stroma
      after deep lamellar keratoplasty.
AB  - PURPOSE: To report clinical and histopathological characteristics of
      postoperative amyloidosis recurrence in a patient with lattice corneal dystrophy
      (LCD) type I. METHODS: The clinical manifestation of recurrent amyloidosis in the
      residual stroma was delineated in a patient with LCD type I after deep lamellar
      keratoplasty (DLKP) for 6.5 years. Complete removal of the residual recipient
      stroma and regrafting of a new cryopreserved donor button were accomplished by a
      secondary DLKP. The primary DLKP donor graft and the underlying residual stroma
      of the recipient obtained by the secondary DLKP were examined for analysis of
      histopathologic and ultrastructural changes. RESULTS: A tongue-shaped retained
      stroma with linear opacity was observed underneath the primary DLKP donor graft.
      The retained stromal layer was thoroughly detached from Descemet membrane,
      removed, and followed by grafting a new cryopreserved button. The primary donor
      button exhibited a normal epithelium, fewer keratocytes, an intact Descemet
      membrane, and mild positive Congo red staining in the middle layer of the stroma.
      The total retained recipient stroma removed by the secondary DLKP measured
      approximately 20 mum in thickness, showing thick and massive amyloid
      accumulation. The surface of the removed residual stroma toward Descemet membrane
      showed collagen fibers in an interwoven fashion without bundle structure under a
      scanning electron microscope. CONCLUSION: Incomplete removal of the recipient
      stroma by DLKP can lead to the recurrence of amyloidosis in the residual stroma
      in patients with LCD. Clinical and histologic findings in the primary graft and
      in the residual recipient stroma implicate stromal genesis of recurrence of LCD
      after DLKP.

PMID- 17001193
TI  - Mechanisms of giant papillary formation in vernal keratoconjunctivitis.
AB  - PURPOSE: Tissue remodeling, known to accompany exacerbation of bronchial asthma
      (BA) and characterized by thickening of reticular basement membrane, increased
      fibrosis, and angiogenesis, is believed to be an important mechanism in giant
      papillary formation in vernal keratoconjunctivitis (VKC). This study was
      conducted to confirm the difference of tissue remodeling between BA and VKC and
      to determine the most relevant factor for VKC exacerbation. METHODS:
      Histopathologic analysis of conjunctival specimens from 6 patients with VKC and 4
      normal controls was performed. Immunohistochemistry tests for collagen types 1,
      3, and 5, fibronectin, laminin (a marker of the basement membrane of the
      epithelium or vessels), fibroblast (prolyl 4-hydroxylase), and alpha-smooth
      muscle actin (alpha-SMA) were performed. Morphometric analysis evaluated
      immunoreactive areas for collagens and fibronectin and the number of cell nuclei
      in VKC papillae and normal control specimens. RESULTS: In histopathologic
      sections of VKC papillae, mononuclear cells were mainly observed in the central
      region and granulocytes preferentially in the peripheral stroma.
      Immunohistochemistry showed increased vascularity and existence of fibroblasts
      and alpha-SMA-positive cells in VKC papillae. Morphometric analysis showed that
      the number of cell nuclei in VKC papillae was 7.3 times higher versus in normal
      controls (P < 0.05). Furthermore, the immunoreactive area for fibronectin was 4.5
      times larger versus in normal controls (P < 0.05), although collagens were not
      significantly different between the 2 groups. CONCLUSION: Giant papillary
      formation in VKC is thought to occur in relation to tissue remodeling. However,
      the most relevant factor for the exacerbation of VKC seems to be inflammation
      rather than fibrosis.

PMID- 17001194
TI  - Immunological characteristics of amniotic epithelium.
AB  - We review recent experimental evidence of the immunosuppressive and immunogenic
      potential of amniotic epithelial cells. Since cryopreserved amniotic membrane
      (AM) has been used in clinical applications, much research has focused on the
      beneficial effects of amniotic stromal matrix rather than on the function of
      viable amniotic cells. However, viable human amniotic epithelial cells (HAECs)
      have been shown to elicit beneficial effects on secretion of anti-inflammatory
      factors. Topical application of culture supernatant from HAECs leads to profound
      suppression of suture-induced neovascularization in cornea and fewer major
      histocompatibility complex (MHC) class II antigen-presenting cells (APCs) in
      inflamed cornea after thermal cautery. Furthermore, expression of interleukin
      (IL)-1beta mRNA was suppressed in cauterized cornea. These results suggest that
      HAECs are a source of soluble anti-inflammatory factors that suppress corneal
      inflammation. However, viable amniotic epithelial cells display antigenicity and
      immunogenicity as allografts. Fresh allogeneic amniotic epithelium (AE) expresses
      MHC class I antigens and sensitizes recipients when placed in the eye, although
      long-term memory of allo-specific delayed hypersensitivity (DH) was not acquired.
      Allogeneic AE was clearly vulnerable to acute immune rejection in specifically
      sensitized recipients and recipients of repeated AE transplantation. We therefore
      suggest that immunogenicity of AE should not be ignored, and use of AM from
      different donor placentas should be emphasized when repeated AM transplantation
      is required in patients clinically.

PMID- 17001195
TI  - Optical quality of the cornea after overnight orthokeratology.
AB  - PURPOSE: To review changes in the optical quality of the cornea induced by
      overnight orthokeratology for myopia. METHODS: Sixty-four eyes of 39 patients who
      underwent overnight orthokeratology for myopia were prospectively examined.
      Inclusion criteria were uncorrected visual acuity of 20/20 or better after
      treatment and a minimum follow-up of 3 months. To quantitatively assess changes
      in corneal regular and irregular astigmatism, videokeratography data were
      decomposed into spherical component, regular astigmatism, asymmetry, and higher
      order irregularity using Fourier analysis. In addition, corneal wavefront
      aberrations were calculated by expanding anterior corneal height data from
      videokeratography into a set of orthogonal Zernike polynomials. RESULTS: Although
      orthokeratology significantly reduced manifest refraction and improved
      uncorrected visual acuity, the asymmetry component, which is one of the features
      of irregular astigmatism, increased significantly from 0.35 +/- 0.22 to 0.64 +/-
      0.40 D after treatment (P < 0.0001, paired t test). The increases in the
      asymmetry component significantly correlated with the amount of myopic correction
      (Pearson correlation coefficient, R = 0.40, P = 0.0009). Furthermore, the root
      mean-square of third-order (coma-like) and fourth-order (spherical-like)
      aberrations significantly increased after orthokeratology (P < 0.0001, paired t
      test), and these increases showed significant positive correlations with the
      amount of myopic correction (Pearson correlation coefficient, R = 0.452, P =
      0.0001 and R = 0.381, P = 0.0017, respectively). CONCLUSION: Corneal irregular
      astigmatism and higher-order aberrations significantly increased even in
      clinically successful orthokeratology, and the increases correlated with the
      magnitude of myopic correction. A large myopic correction by orthokeratology
      should be avoided to not decrease corneal optical quality.

PMID- 17001196
TI  - Effect of oral valaciclovir on herpetic keratitis.
AB  - PURPOSE: To examine the efficacy of valaciclovir (VACV) oral formulation as an
      alternative to topical treatments in a case of herpetic keratitis. METHODS: The
      patient was a 61-year-old man who presented with dendritic keratitis in his left
      eye. After recognizing his difficulty in using eye ointment, we prescribed oral
      VACV 500 mg tablets twice daily for 7 days. We also describe our experiments with
      orally administered VACV in a mouse model of this disease. In this study, 143
      Balb/c mice were inoculated with herpes simplex virus type 1 (HSV)-1 in each eye
      and treated with oral VACV 50 or 100 mg/kg twice daily, oral acyclovir (ACV) 50
      mg/kg 5 times/d, 3% ACV eye ointment (ACV-O) 5 times/d, 3% ACV eye drops 5
      times/d, or control for 5 days. RESULTS: After 7 days, the patient's lesion was
      observed healed. Corrected left visual acuity was also improved, and HSV DNA was
      below detectable level. In the mouse study, slit-lamp examination on days 3, 4,
      5, and 7 revealed that all 5 ACV and VACV treatment groups were significantly
      more effective in improving symptoms of herpetic epithelial keratitis versus
      control (P < 0.05). Moreover, VACV 100 mg/kg was superior to other treatments.
      Viral titers in mouse eyeball and trigeminal ganglia were lowest in the VACV 100
      mg/kg group versus other treatment groups. CONCLUSION: Our case example suggests
      that when frequent application, blurred vision, and foreign body sensation after
      ACV-O application cause difficulty for patients to follow treatment, oral VACV
      might be an effective and safe option for patients with herpetic keratitis.

PMID- 17001197
TI  - Phospholipids and their degrading enzyme in the tears of soft contact lens
      wearers.
AB  - PURPOSE: Low tear phospholipids levels are associated with tear film instability
      in soft contact lens wearers. We assayed levels of phospholipids and their
      degrading enzyme secretory phospholipase A2 (sPLA2) both in tears and deposited
      on contact lenses composed of 2 hydrophilic materials after 1 day of routine use.
      METHODS: Polymacon (Medalist; FDA group 1, low water/nonionic) and Etafilcon A
      (One Day Acuvue; group 4, high water/ionic) contact lenses were worn for 12 hours
      by 16 experienced contact lens wearers. Phospholipids in tear fluids and
      deposited on contact lenses were estimated by phosphorus determination with
      ammonium molybdate through enzymatic digestion. Double-antibody sandwich ELISA
      was used to determine group IIa sPLA2 concentrations, and sPLA2 activity was
      assayed using 1,2-diheptanoyl thio-phosphatidylcholine as substrate. RESULTS:
      Phospholipids concentrations in tears with Polymacon and Etafilcon A were 186 +/-
      39 and 162 +/- 33 microg/mL, respectively. The latter concentration was
      significantly lower than that observed in the same subjects when not wearing
      contact lenses (P = 0.0023). In tears, both group IIa sPLA2 concentrations and
      enzymatic activity remained unchanged, regardless of lens wearing. However,
      Etafilcon A (0.57 +/- 0.09 microg/lens) showed more group IIa sPLA2 deposition
      than Polymacon (0.01 +/- 0.01 microg/lens; P < 0.001). Furthermore, group IIa
      sPLA2 deposited on Etafilcon A but not on Polymacon lenses retained its enzymatic
      activity. CONCLUSION: Significant differences of group IIa sPLA2 deposition were
      found in the 2 lenses tested. Such deposition might induce phospholipid
      hydrolysis in tears and thereby promote tear film instability in hydrophilic
      contact lens wearers.

PMID- 17001198
TI  - Ocular surface tissue morphogenesis in normal and disease states revealed by
      genetically modified mice.
AB  - Many transgenic and knockout mice exhibit pathogenic processes resembling human
      ocular surface diseases. Thus, the clinical manifestations of mouse lines can
      provide clues for identifying heritable human diseases of unknown etiology.
      However, mouse lines using conventional techniques of transgenesis and gene
      targeting often exhibit embryonic lethality and congenital defects, which
      preclude the use of such mouse models to study acquired ocular surface tissue
      diseases. These difficulties can be in part overcome by preparing mouse lines of
      inducible transgene expression, tissue-specific gene ablation, and inducible
      tissue-specific gene ablation. Conditional transgenic mouse lines live normally
      until administration of doxycycline and hormones that induce expression of the
      transgene and ablation of gene of interest. Toward this goal, we prepared 2
      groups of genetically modified mouse lines: (1) transgenesis using keratocan
      promoter was used to create Kera-rtTA mice (doxycycline-inducible mice) and Cre
      LoxP system (ie, Kera-Cre mice; conditional gene ablation in neural crest cell
      lineage and adult stromal keratocyte) and Kera-CrePR mice (RU-486 inducible); and
      (2) knock-in strategies were used to create Krt12-rtTA mice (doxycycline
      inducible), Krt12-Cre mice (conditional ablation in corneal epithelium), and
      Krt12rtTA-tet-O-Cre mice (doxycycline-inducible corneal epithelium-specific gene
      ablation). Using these mouse lines, we showed that transforming growth factor
      (TGF)-beta2 is essential for eye morphogenesis, TGF-alpha is a morphogen for
      eyelid formation, and lumican is a matrikine that has multiple regulatory
      functions on cell activities (eg, migration proliferation and gene expression)
      besides serving as a regulatory molecule of collagen fibrillogenesis. These mouse
      lines can also be used as models for development of therapeutic treatment
      regimens of ocular surface diseases using gene therapy and stem cell strategies.

PMID- 17001199
TI  - Corneal stromal and endothelial cell precursors.
AB  - PURPOSE: To isolate precursors of human corneal stromal and endothelial cells in
      vitro and to compare the distribution of rabbit corneal endothelial cell
      precursors in the central and peripheral regions of the cornea. METHODS: Sphere
      forming cells were isolated from human corneal stromal and endothelial cells by a
      reaggregation-free neurosphere assay. To promote differentiation of the cells,
      the isolated sphere colonies were plated in wells with a medium containing fetal
      bovine serum. Expression of various proteins was examined in the sphere colonies
      and their progeny by immunocytochemistry and reverse-transcriptase polymerase
      chain reaction (RT-PCR). Corneal endothelium and Descemet membrane of rabbits
      were demarcated into peripheral (6.0-10.0 mm in diameter) and central (6.0 mm in
      diameter) regions. Precursor cells were isolated from these 2 regions by sphere
      forming assay, and the number of sphere colonies and size of spheres were
      compared in the central and peripheral regions. RESULTS: Human corneal stromal
      and endothelial cells formed sphere-shaped colonies that expressed mesenchymal
      and neural markers. The rate of sphere formation in the peripheral region of
      rabbit corneal endothelium was significantly higher than that in the central
      cornea. CONCLUSION: Adult human corneal stroma contains precursor cells that have
      a strong propensity to differentiate into mesenchymal fibroblasts, but these
      cells can also differentiate into neuronal lineage. Adult human corneal
      endothelium contains precursors with a propensity to differentiate into corneal
      endothelial cells, but these cells can also produce neuronal and mesenchymal cell
      proteins. The peripheral endothelium of rabbit cornea contains more precursors
      than the central region.

PMID- 17001200
TI  - The brilliant beauty of the eye: light reflex from the cornea and tear film.
AB  - PURPOSE: Light reflex from the cornea and tear film as contributors to beautiful
      eyes ("eye sparkling") are reviewed. METHODS: A systematic literature review was
      conducted using "Purkinje-Sanson image," "corneal light reflex," "corneal
      topography," "corneal wavefront aberration," and "tear interference image" as
      search terms. RESULTS: Articles on corneal surface regularity and stability and
      tear interferometry of the precorneal tear lipid layer were reviewed. PS-1 image,
      that is light reflex from the cornea and tear film, is widely used in practical
      ophthalmic examination. CONCLUSION: To achieve a brilliant beauty of the eye
      ("eye sparkling"), it is important that the tear film (aqueous layer) surface is
      smooth and stable with adequate tear volume and that the tear lipid layer is
      present in adequate thickness.

PMID- 17001201
TI  - Anatomy and histopathology of the human lacrimal gland.
AB  - PURPOSE: To review the anatomy and histopathologic changes of the human main
      lacrimal gland. METHODS: Samples of lacrimal gland including palpebral lobes and
      orbital lobes were taken in autopsies, and the relationship between
      histopathologic changes and age and sex, as well as histopathologic differences
      between palpebral and orbital lobes of the lacrimal gland, were studied using
      light microscopy. RESULTS: Various histopathologic changes were observed in the
      human main lacrimal gland as follows: acinar atrophy; periacinar fibrosis;
      periductal fibrosis; interlobular ductal dilatation; interlobular ductal
      proliferation; lymphocytic infiltration; and fatty infiltration. Several
      histopathologic differences exist between the palpebral and orbital lobes. There
      were statistically significant correlations between age and diffuse fibrosis,
      diffuse atrophy, and periductal fibrosis in the orbital lobes of women. Diffuse
      fibrosis and diffuse atrophy in orbital lobes were more frequently observed in
      women than in men. CONCLUSION: It is speculated that periductal fibrosis is
      related to a decrease of tear flow with age and that interlobular ductal
      dilatation in palpebral lobes may be caused by stenosis of the excretory duct in
      conjunctival fornix. However, the mechanisms of these histopathologic changes in
      the human main lacrimal gland are not yet clear.

PMID- 17001202
TI  - Isolation of human corneal endothelial cell precursors and construction of cell
      sheets by precursors.
AB  - PURPOSE: To review recently published experimental data on human corneal
      endothelium (CE) precursors. METHODS: A sphere-forming assay was used for the
      isolation of human CE precursors from human donor corneas and cultured human CE.
      CE morphology derived from precursors was compared with that from cultured human
      CE. RESULTS: Human CE from donor corneas formed primary and secondary sphere
      colonies and expressed neural and mesenchymal proteins. The progeny of these
      colonies had a human-CE-like hexagonal shape and showed transport activity,
      suggesting that the isolated spheres were indeed precursors of human CE. Similar
      precursors were isolated from cultured human CE, which provided further evidence
      that the sphere-forming assay facilitates the mass production of human CE
      precursors. Cultured human CE obtained in this manner had a regular hexagonal
      morphology in contrast to passaged, cultured human CE. CONCLUSION: The sphere
      forming assay may become a powerful tool for the regeneration of human CE by
      precursor injection and the construction of cultured CE sheets.

PMID- 17001203
TI  - Coronary revascularization and medical management of coronary artery disease:
      changing paradigms and perceptions.

PMID- 17001204
TI  - Cardiovascular risk prediction systems have to be adapted and updated to current
      national conditions.

PMID- 17001205
TI  - Recommendations for participation in leisure-time physical activity and
      competitive sports of patients with arrhythmias and potentially arrhythmogenic
      conditions. Part II: ventricular arrhythmias, channelopathies and implantable
      defibrillators.
AB  - This consensus paper on behalf of the Study Group on Sports Cardiology of the
      European Society of Cardiology follows a previous one on guidelines for sports
      participation in competitive and recreational athletes with supraventricular
      arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias
      is especially relevant when some form of ventricular rhythm disorder is
      documented, or when the patient is diagnosed to have inherited a pro
      arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained
      ventricular tachycardia may be a hallmark of underlying pathology and increased
      risk. Their finding should prompt a thorough cardiac evaluation, including both
      imaging modalities and electrophysiological techniques. This should allow
      distinguishing idiopathic rhythm disorders from underlying disease that carries a
      more ominous prognosis. Recommendations on sports participation in inherited
      arrhythmogenic conditions and asymptomatic gene carriers are also discussed:
      congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome,
      catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right
      ventricular cardiomyopathy and other familial electrical disease of unknown
      origin. If an implantable cardioverter defibrillator is indicated, it is no
      substitute for the guidelines relating to the underlying pathology. Moreover,
      some particular recommendations for patients/athletes with an implantable
      cardioverter defibrillator are to be observed.

PMID- 17001206
TI  - ESC study group of sports cardiology position paper on adverse cardiovascular
      effects of doping in athletes.
AB  - The use of doping substances and methods is extensive not only among elite
      athletes, but also among amateur and recreational athletes. Many types of drugs
      are used by athletes to enhance performance, to reduce anxiety, to increase
      muscle mass, to reduce weight or to mask the use of other drugs during testing.
      However, the abuse of doping substances and methods has been associated with the
      occurrence of numerous health side-effects. The adverse effects depend on the
      type of the consumed drug, as well as the amount and duration of intake and the
      sensitivity of the body, since there is a large inter-individual variability in
      responses to a drug. Usually the doses used in sports are much higher than those
      used for therapeutic purposes and the use of several drugs in combination is
      frequent, leading to higher risk of side-effects. Among biomedical side-effects
      of doping, the cardiovascular ones are the most deleterious. Myocardial
      infarction, hyperlipidemia, hypertension, thrombosis, arrythmogenesis, heart
      failure and sudden cardiac death have been noted following drug abuse. This paper
      reviews the literature on the adverse cardiovascular effects after abuse of
      prohibited substances and methods in athletes, aiming to inform physicians,
      trainers and athletes and to discourage individuals from using drugs during
      sports.

PMID- 17001207
TI  - Job stress and major coronary events: results from the Job Stress, Absenteeism
      and Coronary Heart Disease in Europe study.
AB  - AIMS: The intention of this study is to investigate the relationship of the
      demands/control/strain model with hard coronary events in an epidemiological,
      prospective, multicenter, European study. METHODS AND RESULTS: Six cohorts
      (Brussels, Ghent, Lille, Barcelona, Goteborg and Malmo) from four European
      countries (Belgium, France, Spain and Sweden) consisting of 21 111 middle-aged
      male subjects participated between 1993 and 1996 in the baseline survey of the
      Job Stress, Absenteeism and Coronary Heart Disease in Europe (JACE) study. The
      Karasek strain model of psychological demands (five items)/control (nine items)
      was used. During a mean follow-up of 40 months 185 acute coronary events or
      coronary deaths were observed. Age-adjusted hazard ratios (HRs) for developing an
      acute coronary event were 1.46 [CI 95% confidence interval (1.08-1.97)] for high
      against low psychological demands and 1.53 (95% CI 1.0-2.35) for strained (high
      demands plus low control) against relaxed (low demands plus high control) groups.
      After adjustment for standard cardiovascular risk factors the HR for developing a
      coronary event for those above or equal to the median against those below the
      median of psychological demands was 1.46 (95% CI 1.08-1.97) whereas the HR for
      strained against relaxed groups is 1.46 (95% CI 0.96-2.25). Sensitivity analyses
      confirmed the robustness of the results. CONCLUSION: In this European,
      multicenter, prospective, epidemiological study the Karasek job strain model was
      an independent predictor of acute coronary events, with the psychological demands
      scale emerging as the important component.

PMID- 17001208
TI  - Endothelial progenitor cells: a new target for the prevention of cardiovascular
      diseases.
AB  - Endothelial progenitor cells (EPCs) are circulating precursor cells that have
      been implicated recently in vascular and cardiac regeneration. There is an
      ongoing discussion on the immunocytological definition of EPCs, based on various
      surface markers, and currently different cell types are included in the term
      'EPC'. This review summarizes the mechanisms that influence function, survival,
      mobilization and differentiation of EPCs. Furthermore, there are several reports
      on the clinical use of EPCs for the treatment of cardiovascular diseases. We have
      focused specifically on the influence of physical activity on EPC function.

PMID- 17001209
TI  - How to improve screening in first-degree relatives of patients with premature
      coronary heart disease.
AB  - BACKGROUND: Guidelines on the prevention of cardiovascular disease recommend
      screening in close relatives of patients with premature coronary heart disease
      (CHD). This family history puts them at increased risk for CHD, independent of
      other major risk factors, but screening for CHD risk factors in these relatives
      is not widely practiced in Europe. This demonstration project examined how to
      improve screening of close relatives of patients with premature CHD in daily
      practice. METHODS: A controlled study design was used. Four hospitals were
      compared in a pre-test as to the actual screening of relatives of patients with
      premature CHD. Then they were arranged in pairs and randomly assigned to the
      Usual care (U) or Intervention group (I). An information and health education
      program--involving patients, relatives and family doctors--was developed in I to
      improve screening by the family doctor. RESULTS: The pre-test confirmed that
      screening of relatives of patients with premature CHD is poorly practiced in the
      four regions; no significant differences between I and U were observed. The
      screening of relatives during the study period reached 63.9% in I compared to
      25.4% in U. This difference between I and U was present in siblings and
      offspring. The cardiovascular risk profile of the relatives of I was not optimal
      and needed improvement. CONCLUSION: Screening of first-degree relatives of
      patients with premature CHD can be significantly improved through a health
      education program. This is the first and necessary step to improve the management
      of risk factors in these people, who are at increased risk for CHD.

PMID- 17001210
TI  - Awareness, knowledge, and perception of heart disease among adolescents.
AB  - BACKGROUND: Perceptions of cardiovascular risk among adolescents have not been
      studied recently. The rise in unattended risk factors and the obesity pandemic
      have created calculable cardiovascular disease risk in the adolescent population.
      DESIGN: We sought to assess the awareness, level of knowledge, and perception of
      cardiovascular disease in an adolescent population. METHODS: We administered a
      survey designed to collect data on demographics, beliefs regarding risk factor
      importance, perceived future risk and other knowledge-based assessment questions
      about cardiovascular disease. RESULTS: Students, n=873, (45.4% male, mean age
      15.6 years) in grades 9-12, from four Michigan high schools completed the survey
      unassisted. Accidents were rated as the greatest perceived lifetime health risk
      (39.1%). A minority (16.6%) of respondents selected cardiovascular disease as the
      greatest lifetime risk placing it behind accidents and cancer. When asked to
      identify the greatest cause of death for each sex, 42.3% of respondents correctly
      recognized cardiovascular disease for men and 14.0% correctly recognized
      cardiovascular disease for women in the United States, P<0.0001. Forty percent of
      respondents incorrectly chose a substance abuse/use behavior, other than
      cigarettes, as the most important cardiovascular disease risk behavior.
      CONCLUSIONS: Our findings suggest that adolescents lack knowledge regarding the
      risk of cardiovascular disease and do not perceive themselves at risk for
      cardiovascular disease. These data will be useful in designing future preventive
      strategies and interventions aimed at this target population.

PMID- 17001211
TI  - Patients' beliefs about the causes of heart disease: relationships with risk
      factors, sex and socio-economic status.
AB  - BACKGROUND: Patients' beliefs about the causes of their heart disease (causal
      attributions) are important to effective medical communication, psychological
      adaptation, and adherence to advice. We assessed the extent to which causal
      attributions relate to risk factors, sex and socio-economic status in men and
      women diagnosed with acute coronary syndrome. DESIGN: We conducted an interview
      and questionnaire study of 171 acute coronary syndrome patients assessed within 5
      days of admission to three hospitals in the London area. METHOD: Patients rated
      beliefs in the role of 16 factors in causing their heart disease. Associations
      between attributions and risk factors were assessed, and differences in beliefs
      by sex and socio-economic status (defined by educational attainment) analysed.
      RESULTS: The most common attributions were to stress, smoking, high blood
      pressure, chance or bad luck, and heredity. Attributions were strongly associated
      with risk factors: 90% of smokers attributed heart disease to smoking, compared
      with 0% never smokers; 90.4% of hypertensives attributed heart disease to high
      blood pressure, 72.2% of patients with a positive family history to heredity, 85%
      of obese patients to being overweight, and 49% of sedentary patients to lack of
      exercise. Attributions to stress were related both to current mood and reports of
      recent life stress. There were few sex differences, but higher socio-economic
      status patients were more likely to attribute heart disease to heredity and
      genetic factors. CONCLUSIONS: Causal beliefs about heart disease are strongly
      associated with risk factors. Effective communication about modifiable risk
      factors may influence causal beliefs and stimulate lifestyle change, thereby
      promoting secondary prevention.

PMID- 17001212
TI  - The SCORE risk model applied to recent population surveys in Norway compared to
      observed mortality in the general population.
AB  - AIMS: To compare the predictions of the Systematic Coronary Risk Evaluation
      (SCORE) high- and low-risk functions applied to a recent population study with
      observed cardiovascular disease (CVD) mortality estimated from annual official
      mortality statistics in Norway. METHODS: Data were obtained from large
      epidemiological surveys conducted in five Norwegian counties in 2000-2003.
      RESULTS: A total of 32 251 men and women were investigated (aged 30-31, 40-41, 45
      46, and 59-61). For men aged >or=59, more than 75% qualified for preventive
      treatment by having a 10-year risk >or=5%. Few women and practically no men
      younger than 46 years can be considered at high risk according to the SCORE risk
      prediction models. For men, the high-risk function overestimated and the low-risk
      model underestimated the CVD mortality as compared to the 10-year risks
      calculated from official mortality statistics (1999-2003). For women, however,
      both functions underestimated mortality in young individuals, whereas in the
      elderly an overestimation was observed. CONCLUSIONS: The risk predictions
      depended strongly on age and gender. The SCORE high-risk function overestimates
      the risk of fatal CVD for men in Norway, and before implementation in clinical
      practice, proper adjustments to national levels are required.

PMID- 17001213
TI  - Relationship of classical and non-classical risk factors with genetic variants
      relevant to coronary heart disease.
AB  - BACKGROUND: In addition to the well established cardiovascular risk factors,
      evidence suggests a possible role of genetic and non-classical risk factors in
      the development and progression of atherothrombosis. We aimed to determine the
      relationship of classical and non-classical cardiovascular risk factors with
      candidate gene polymorphisms potentially involved in cardiovascular risk in the
      general Mediterranean population. DESIGN: Cross-sectional study. METHODS: We have
      determined the prevalence of classical (lipid profile, blood pressure, glycaemia,
      diabetes, smoking, body mass index, menopause and family history of coronary
      heart disease) and non-classical cardiovascular risk factors (infectious
      processes, homocysteinaemia, oxidative status, C-reactive protein, lipoprotein
      (a) and fibrinogen) in a population-based study. We analysed the relationship of
      these risk factors with the following five gene polymorphisms potentially
      involved in cardiovascular risk: ATP-binding cassette transporter A1-R219K,
      Peroxisome proliferator-activated receptor (PPAR)-alpha-L162V, Lipoprotein lipase
      (LPL)-HindIII, Paraoxonase (PON)1-Q192R, and Tumour necrosis factor (TNF)-alpha-G
      308A. RESULTS: We found PPAR-alpha-V and LPL-H alleles to be associated with
      decreased high-density lipoprotein-cholesterol (HDL-c) concentration and with
      increased total cholesterol : HDL-c and triglyceride : HDL-c ratios. Regarding
      the non-classical risk factors, C-reactive protein concentration was higher for
      the PPAR-alpha-V allele. A higher oxidative status was shown in homozygotes for
      LPL-H and TNF-alpha-G alleles, although the latter also had lower
      homocysteinaemia. CONCLUSIONS: Three of the genetic variants analysed, PPAR-alpha
      L162V, LPL-HindIII, and TNF-alpha-G-308A, were associated with non-classical risk
      factors, specifically lipid profile, inflammation, and oxidative status.

PMID- 17001214
TI  - Distribution of lifestyle and emerging risk factors by 10-year risk for coronary
      heart disease.
AB  - BACKGROUND: The Framingham risk score has been used for coronary heart disease
      (CHD) risk assessment. Recently, additional risk factors not included in the
      Framingham algorithm have received much attention and may help improve risk
      assessment. We examined the distributions of lifestyle and emerging risk factors
      by 10-year risk of CHD. METHODS: We calculated 10-year CHD risk (<10%, 10-20%,
      and >20%) for 8355 participants in the National Health and Nutrition Examination
      Survey (NHANES) 1999-2002 using the Framingham risk score as modified by the
      National Cholesterol Education Program Adult Treatment Panel III guidelines. We
      examined the prevalence of lifestyle risk factors [body mass index (BMI) and
      waist circumference] and various emerging risk factors [C-reactive protein (CRP),
      white blood cell count, fibrinogen, homocysteine, glycosylated hemoglobin, and
      albuminuria] as well as prevalence of high CHD risk by levels of these risk
      factors. RESULTS: All examined CHD risk factors were significantly associated
      with increasing 10-year CHD risk among men and women. Odds of being in the
      highest CHD risk group were greater at higher levels of examined risk factors.
      Means for most risk factors were slightly higher for women than the means for
      men. Sizeable proportions of participants with lower 10-year CHD risk had high
      levels of lifestyle and emerging risk factors: 60.8% were overweight, 33.8% had
      high CRP concentrations, 24.1% had serum fibrinogen >400 mg/dl and 6% had an
      albumin/creatinine ratio >/=30. CONCLUSIONS: Lifestyle and emerging risk factors,
      in addition to those included in the Framingham risk score, may be important in
      CHD risk assessment.

PMID- 17001215
TI  - Burden of ischaemic heart disease and cerebrovascular diseases in Serbia without
      Kosovo and Metohia, 2000.
AB  - BACKGROUND: To provide estimates of cardiovascular disease burden to guide future
      health strategies and interventions and enable improvements in health and
      performance of the health care system to be monitored. DESIGN: A descriptive
      study. METHODS: The study was performed in Serbia without Kosovo and Metohia for
      the year 2000. Disability-adjusted life years (DALY) was used to provide a
      comprehensive assessment of premature mortality (years of life lost; YLL) and
      disability attributable (years lived with disability; YLD) to ischaemic heart
      disease (IHD) and cerebrovascular diseases, and to estimate the attributable and
      avoidable burden of these diseases caused by smoking, hypertension,
      overweight/obesity, physical inactivity, alcohol consumption and an inadequate
      consumption of fruit and vegetables. RESULTS: IHD was responsible for 150 889
      DALY (16.28/1000 population), and cerebrovascular diseases were responsible for
      136 090 DALY (14.49/1000 population). There were considerably more YLL for both
      IHD and stroke than YLD. For both diseases DALY rates increased with ageing in
      men and women. The risk factors most responsible for IHD and stroke burden were
      smoking, physical inactivity, hypertension and overweight/obesity. Sex and age
      differences were present in the burden attributable to various risk factors.
      CONCLUSION: Despite limitations the DALY estimates represent a useful measure of
      the size of the health problem. The DALY and related estimates for cardiovascular
      disease can be used as a guide for the prevention of IHD and stroke as well as
      the evaluation of future health gains by reducing population exposure to
      lifestyle and related risk factors.

PMID- 17001216
TI  - Contribution of changes in risk factors to the decline of coronary heart disease
      mortality in Australia over three decades.
AB  - BACKGROUND: Coronary heart disease has been a major cause of mortality in
      Australian adults, but the rate has declined by 83% from the 1968 peak by the
      year 2000. The study objective is to determine the contribution of changes in
      population risk factors - mean serum cholesterol and diastolic blood pressure and
      tobacco smoking prevalence - to the decline in coronary heart disease mortality
      in Australia over three decades. METHODS: Coronary heart disease deaths
      (International Classification of Disease-9, 410-414) and population by year, age
      group and sex were obtained from the Australian Bureau of Statistics. Risk factor
      levels were obtained from population surveys and estimated average annual changes
      by period were used to calculate average annual 'attributable' proportional
      declines in CHD mortality by period (age 35-64 years). RESULTS: Over the period
      1968-2000, 74% of male decline and 81% of the female decline in coronary heart
      disease mortality rate was accounted for by the combined effect of reductions in
      the three risk factors. In males 36% of the decline was contributed by reductions
      in diastolic blood pressure, 22% by cholesterol and 16% by smoking. For females
      56% was from diastolic blood pressure reduction, 20% from cholesterol and 5% from
      smoking. Effects of reductions in serum cholesterol on coronary heart disease
      mortality occurred mainly in the 1970s. Declines in diastolic blood pressure had
      effects on coronary heart disease mortality over the three decades, and declines
      in tobacco smoking had a significant effect in males in the 1980s. CONCLUSION:
      Most of the spectacular decline in coronary heart disease mortality over the last
      three decades in Australia can be ascribed to reductions in population risk
      factors from primary and secondary prevention.

PMID- 17001217
TI  - Prevalence and impact of cardiovascular risk factors in Bucaramanga, Colombia:
      results from the Countrywide Integrated Noncommunicable Disease Intervention
      Programme (CINDI/CARMEN) baseline survey.
AB  - BACKGROUND: Although cardiovascular diseases are the main cause of death in the
      region, there are few data on the prevalence of cardiovascular risk factors in
      Latin American. We studied the distribution and impact of cardiovascular risk
      factors in Bucaramanga, Colombia. METHODS: We conducted a cross-sectional study
      in a random sample of 2989 subjects 15-64 years old. Population attributable
      risks were estimated from Framingham risk scores. RESULTS: Smoking prevalence was
      16.2% (men 26.3%; women 10.5%). Hypertension prevalence was 9.9% in women and
      8.8% in men, but reached 50% in those 60-64 years old. After adjustment for body
      mass index, men were more likely to be hypertensive, but only if under 40 years
      old. Obesity was more frequent in women (15.7%) than in men (8.7%), even after
      age-adjustment. About 46% of the participants were overweight or obese. Women
      also had higher prevalence of high total cholesterol (19.7 versus 15.7%) and high
      low-density lipoprotein-cholesterol (23.9 versus 19.5%), but lower prevalence of
      low high-density lipoprotein (HDL)-cholesterol (22.2 versus 37.6%). Only low-HDL
      prevalence was significantly different after body mass index and age-adjustment.
      The prevalence of diabetes was similar in men and women (4%), but age and body
      mass index-adjusted impaired fasting glucose prevalence was 60% higher in women.
      Population attributable risks were larger and similar for high total cholesterol,
      hypertension, and large waist-to-hip ratio (19%). CONCLUSIONS: Women had higher
      prevalence of all risk factors with the exception of smoking and low-HDL.
      Reduction in cholesterol levels, blood pressure and obesity is a priority to
      control the ongoing epidemic of cardiovascular diseases in this population.

PMID- 17001218
TI  - Gap between guidelines and practice: attainment of treatment targets in patients
      with primary hypercholesterolemia starting statin therapy. Results of the 4E
      Registry (Efficacy Calculation and Measurement of Cardiovascular and
      Cerebrovascular Events Including Physicians' Experience and Evaluation).
AB  - BACKGROUND: The aim of this study was to determine the achievement of National
      Cholesterol Education Program Adult Treatment Panel III goals in patients with
      primary hypercholesterolemia starting statin therapy in clinical practice.
      METHODS AND RESULTS: Data were collected by 4401 physicians in private practice
      on 52 848 patients aged 35-65 years (46.3% women, 53.7% men). 56.1% of patients
      had no manifested atherosclerosis (primary prevention) among whom 34.9% of men
      and 0.5% of women had a 10-year coronary heart disease risk over 20% (high-risk)
      as calculated using the Prospective Cardiovascular Munster study (PROCAM)
      algorithm. After 6 weeks of statins, only 6.9% of these high-risk men and 4.6% of
      these high-risk women reached their low-density lipoprotein (LDL) cholesterol
      target of 2.6 mmol/l or below (100 mg/dl). Even after 9 months, only 8.0% of
      these men and 6.2% of these women achieved their LDL target. No fewer than 57.3%
      of treated women had a coronary risk below 10%, and 18.8% of women were already
      at target before statins were prescribed. Of patients 43.9% had manifest
      atherosclerosis (secondary prevention). After 6 weeks of therapy, only 12.9% of
      the women and 16.3% of the men in this secondary prevention group reached LDL
      target levels of 2.6 mmol/l or below. Even after 9 months, only 21.3% of men and
      17.3% of women with manifest atherosclerosis reached target LDL. CONCLUSIONS:
      Most high-risk patients do not achieve LDL targets. Overtreatment of low-risk
      groups is also very common.

PMID- 17001219
TI  - Prevalence and characteristics of impaired glucose metabolism in patients
      referred to comprehensive cardiac rehabilitation: the DANSUK study.
AB  - BACKGROUND: Lifestyle and pharmacological interventions can delay the progression
      of impaired glucose tolerance (IGT) to type 2 diabetes (T2DM), and there is
      growing evidence that earlier detection of T2DM and intensified risk factor
      management may result in improved cardiovascular morbidity and mortality. We
      studied the prevalence of impaired glucose metabolism (T2DM, IGT and impaired
      fasting glucose; IFG) in patients referred to cardiac rehabilitation, and further
      studied whether we could identify groups in which an oral glucose tolerance test
      (OGTT) need not be performed. METHODS: As part of a cardiac rehabilitation trial,
      201 patients participated. Patients without a diagnosis of T2DM (N=159) underwent
      an OGTT 3 months after inclusion. RESULTS: Forty-two patients (21%) had known
      T2DM at enrolment. Based on the OGTT, 26 patients (13%) had unrecognized T2DM, 36
      (18%) had IGT and 19 (9%) were diagnosed with isolated IFG according to the World
      Health Organization definition. Using fasting plasma glucose alone, 19% of the
      patients with unrecognized T2DM and two-thirds of patients with IGT would be
      misclassified. Using IFG as a means to detect IGT showed a sensitivity of only
      33% and a positive predictive value of 39%. CONCLUSION: More than 60% of the
      patients (123/201) referred to cardiac rehabilitation had impaired glucose
      metabolism and 18% of the screened patients (29/159) would be misclassified if an
      OGTT was omitted. IFG and IGT did not identify the same patients or the same
      cardiovascular risk profile. An OGTT test should therefore be considered a
      constituent part of routine care management in cardiac rehabilitation settings.

PMID- 17001220
TI  - Modelling dairy intake on the development of acute coronary syndromes: the
      CARDIO2000 study.
AB  - BACKGROUND: Dairy consumption may be associated with a small but worthwhile
      reduction in cardiovascular disease risk, but results from epidemiological
      studies are inconsistent. The aim of the present study was to evaluate the
      association between dairy consumption and the prevalence of a first, non-fatal
      event of an acute coronary syndrome, in a Greek sample. DESIGN: Seven hundred
      male and 148 female patients with first event of an acute coronary syndrome and
      1078 population-based controls, age and sex matched, were randomly selected.
      METHODS: Detailed information regarding their medical records, alcohol intake,
      physical activity and smoking habits was recorded. Nutritional habits were
      evaluated with a semi-quantitative food-frequency questionnaire. Multiple
      logistic regression analysis estimated the odds ratio of having acute coronary
      syndrome by level of dairy intake, after taking into account the effect of
      several confounders. RESULTS: An inverse relationship was observed between dairy
      products consumption and odds of having acute coronary syndrome. One portion
      increase in weekly dairy products intake was associated with 12% lower likelihood
      of having acute coronary syndrome, after controlling for various potential
      confounders (P<0.001). Cut-off analysis showed that 7.4 portions per week are the
      optimal consumption that benefits people from having acute coronary syndrome.
      CONCLUSIONS: Dairy consumption seems to offer significant protection against
      coronary heart disease, irrespective of various clinical, lifestyle and other
      characteristics of the participants.

PMID- 17001221
TI  - A single weekly bout of exercise may reduce cardiovascular mortality: how little
      pain for cardiac gain? 'The HUNT study, Norway'.
AB  - BACKGROUND: The observation that exercise training reduces cardiovascular
      mortality is robust and consistent, but the amount and intensity of exercise that
      is required for risk reduction is not yet resolved. METHODS: We studied the
      association between the amount and intensity of exercise and cardiovascular
      mortality in 27 143 men and 28 929 women who were free from known cardiovascular
      disease at the beginning of follow-up between 1984 and 1986. The relative risk of
      death was calculated as the rate of death among participants within a given
      physical activity category compared with the rate of death in the reference
      category (no physical activity). We used Cox regression analysis to adjust for
      age and other potentially confounding factors. RESULTS: After 16 years (SD 4
      years) of follow-up, 2946 men (10.8%) and 2486 women (8.6%) had died from
      ischaemic heart disease or stroke. A single weekly bout of exercise of high
      intensity reduced the risk of cardiovascular death, both in men [relative risk
      (RR) 0.61, 95% confidence interval (CI) 0.49-0.75], and women (RR 0.49, 95% CI
      0.27-0.89), compared with those who reported no activity. There was no additional
      benefit from increasing the duration or the number of exercise sessions per week.
      The risk reduction related to exercise increased with increasing age in men, but
      not in women. CONCLUSION: These results challenge the current recommendation that
      expenditure of at least 1000 kcal per week is required to achieve exercise
      induced protection against premature cardiovascular mortality.

PMID- 17001222
TI  - Habitual aerobic exercise is associated with smaller femoral artery intima-media
      thickness with age in healthy men and women.
AB  - BACKGROUND: Femoral artery intima-media thickness (IMT), an independent predictor
      of atherosclerotic disease risk, increases with age in sedentary adults. It is
      not known whether regular aerobic exercise modulates femoral IMT with ageing.
      METHODS AND RESULTS: Study 1: Femoral IMT was measured in 173 sedentary,
      moderately active, and endurance-trained young (20-39 years), middle-aged (40-59
      years) and older (60-79 years) men. IMT increased with age in all activity groups
      (P<0.001). However, IMT was 20-27% smaller in age-matched, endurance-trained
      compared with sedentary men (P<0.001), and the age-associated increase in IMT was
      33% smaller in endurance-trained compared with sedentary men (+0.32 versus +0.45
      mm). There was a trend for the IMT to be smaller in moderately active compared
      with sedentary older men, and the age-associated increase in IMT was 37% smaller
      in moderately active than sedentary men (+0.28 mm). Study 2: Among 74
      premenopausal and postmenopausal sedentary or endurance-trained women, IMT was
      higher (P<0.001) in postmenopausal compared with premenopausal women regardless
      of activity status. However, IMT was 15% smaller in endurance-trained compared
      with sedentary postmenopausal women (P<0.001), and the premenopausal to
      postmenopausal difference in IMT was approximately 45% smaller in endurance
      trained compared with sedentary women (+0.13 versus +0.23 mm). CONCLUSIONS:
      Femoral IMT increases with age even in habitually exercising adults. However, the
      age-associated increase and absolute level of IMT are smaller in middle-aged and
      older adults who perform regular aerobic-endurance exercise, and may contribute
      to their lower incidence of atherosclerotic disease.

PMID- 17001223
TI  - Effect of physical training on exercise capacity, gas exchange and N-terminal pro
      brain natriuretic peptide levels in patients with chronic heart failure.
AB  - BACKGROUND: Decreased exercise capacity is the main factor restricting the daily
      life of patients with chronic heart failure. N-terminal pro-brain natriuretic
      peptide (NT pro-BNP) is strongly related to the severity of and is an independent
      predictor of outcome in chronic heart failure. DESIGN: The study aimed to
      evaluate the effect of exercise training on functional capacity and on changes in
      NT pro-BNP levels and to assess the effect of exercise training on quality of
      life. MATERIALS AND METHODS: Sixty patients (45 men/15 women, mean age 52.7
      years; +/-5.3 SD), with stable heart failure (45 ischaemic/hypertensive and 15
      idiopathic patients), in New York Heart Association (NYHA) functional class II
      (n=35) to III (n=25), with an ejection fraction less than 40%, were randomly
      assigned to a training (n=30) and a control group (n=30). The training group (30
      patients) performed 3 months of supervised physical training programme using a
      bicycle ergometer for 30 min three times a week at a load corresponding to 60-70%
      of their oxygen consumption (VO2) peak. The control group did not change their
      previous physical activity. A graded maximal exercise test with respiratory gas
      analysis and an endurance test with constant workload corresponding to 85% of the
      peak oxygen load at the baseline and after 3 months were performed, and at the
      same times NT pro-BNP levels were measured. RESULTS: The exercise capacity
      increased from 15.8 (+/-2.3 SD) to 29.9 (+/-2.1 SD) min (P<0.0001) and the peak
      VO2 tended to improve from 14.5 (+/-1.4 SD) to 17.7 (+/-2.6 SD) ml/kg per min
      (P<0.0001) during the supervised training period. VO2 at the anaerobic threshold
      increased from 12.9 (+/-1.0 SD) to 15.5 (+/-1.7 SD) ml/kg per min (P<0.0001). NT
      pro-BNP levels decreased from 3376 (+/-3133 SD) to 1434 (+/-1673 SD) pg/ml
      (P=0.043). The positive training effects were associated with an improvement in
      the NYHA functional class. CONCLUSION: Physical training of moderate intensity
      significantly improves the exercise capacity and neurohormonal modulation in
      patients with chronic heart failure. This is associated with an alleviation of
      symptoms and improvement in quality of life.

PMID- 17001224
TI  - Moderate exercise training improves functional capacity, quality of life, and
      endothelium-dependent vasodilation in chronic heart failure patients with
      implantable cardioverter defibrillators and cardiac resynchronization therapy.
AB  - BACKGROUND: The objective of this study was to determine the effects of a
      moderate exercise training program on functional capacity, quality of life, and
      hospital readmission rate in chronic heart failure patients with implantable
      cardioverter defibrillators and cardiac resynchronization therapy. METHODS AND
      RESULTS: We studied 52 men (mean age 55+/-10 years, ejection fraction 31+/-7%) in
      chronic heart failure II (n=29) and III (n=23) NYHA functional class with
      ischemic cardiomyopathy who received implantable cardioverter defibrillators with
      or without cardiac resynchronization therapy. Patients were randomized into two
      groups. Group T (n=30 patients, 15 implantable cardioverter defibrillator, 15
      implantable cardioverter defibrillator+cardiac resynchronization therapy)
      underwent a supervised exercise training program at 60% of peak VO2 three times a
      week for 8 weeks. Group C (n=22 patients, 12 implantable cardioverter
      defibrillator, 10 implantable cardioverter defibrillator+cardiac
      resynchronization therapy) avoided physical training. At 8 weeks, only trained
      patients had improvements in peak VO2 (P<0.01 versus C), endothelium-dependent
      dilatation of the brachial artery (P<0.001 versus C) and quality of life (P<0.001
      versus C). Among trained patients, those with cardiac resynchronization therapy
      had greater improvements in peak VO2 and quality of life. During the follow-up
      (24+/-6 months), eight controls had sustained ventricular tachycardia requiring
      hospital readmission, while no trained patients had adverse events (log rank
      8.56; P<0.001). The improvement in peak VO2 was correlated with the improvement
      in endothelium-dependent dilatation (r=0.65). CONCLUSION: Moderate exercise
      training is safe and has beneficial effects after implantable cardioverter
      defibrillator implantation, especially when cardiac resynchronization therapy is
      present. These effects are associated with improvement in quality of life and
      outcome.

PMID- 17001225
TI  - Both T-786C and G894T polymorphism of endothelial nitric oxide synthase affect in
      vitro endothelium-dependent relaxation of internal mammary artery rings from
      patients with coronary artery disease.
AB  - OBJECTIVES: Polymorphisms of endothelial nitric oxide synthase (eNOS) gene in the
      promoter (T-786C) and exon 7 (G894T) have been suggested to attenuate endothelial
      function. As it is unknown whether these polymorphisms, on top of classical risk
      factors, further deteriorate endothelium-dependent vasomotion, we aimed to
      elucidate the impact of both polymorphisms on the ex-vivo vasomotor function of
      left internal mammary artery rings from patients with coronary artery disease
      (CAD) undergoing coronary bypass surgery (CABG). METHODS: Mammary artery rings
      from 51 consecutive patients with CAD were obtained during elective CABG.
      Endothelium-dependent ring relaxation was measured in vitro in an organ chamber
      using acetylcholine (10 to 3 x 10 mol/l). Polymorphisms were determined by
      polymerase chain reaction restriction length polymorphism. RESULTS: Thirty-three
      per cent of patients were positive for the T-786C polymorphism, 25% for the G894T
      polymorphism, and 18% carried mutated alleles in both loci. Maximal acetylcholine
      induced ring relaxation was 46.7+/-3.2% in T-786C, 59.6+/-4.2% in G894T, and
      66.7+/-7.4% in T-786C/G894T compared with 94.9+/-2.0% in wild-type subjects
      (P<0.05 versus T-786C, G894T, T-786C/G894T). Patients positive for an eNOS
      polymorphism with more than three cardiovascular risk factors displayed a further
      attenuation of acetylcholine-mediated relaxation (45+/-6 %) compared with having
      up to three risk factors (59+/-3%, P<0.05). CONCLUSION: In patients with CAD, in
      vitro assessed endothelium-dependent relaxation of mammary arteries was
      significantly impaired in those positive for the T-786C or the G894T eNOS
      polymorphism. These results suggest that the presence of either one of the eNOS
      polymorphisms deteriorated endothelium-dependent vasodilatory capacity of large
      conduit vessels on top of classical risk factors in patients with CAD.

PMID- 17001226
TI  - Attempt to eliminate health inequalities in Poland arising at the time of
      political and economic transformation: Polish 400 Cities Project.
AB  - AIM: Epidemiological data show that citizens of small towns and villages have
      presented worse trends in cardiovascular mortality during the political, social
      and economic transformation in Poland during past 15 years than citizens of large
      towns. To try to eliminate these inequalities the Polish 400 Cities Project
      (P400CP), a large educational and interventional project, was prepared. The
      project consists of two arms: medical and social interventions. MATERIAL AND
      METHODS: The main aim of the medical screening intervention in P400CP is to
      increase detection and control of cardiovascular risk factors in inhabitants of
      418 small cities (<8000 inhabitants) and surrounding villages, particularly in
      men and people of lower education. In 2003 and 2004 the P400CP covered 123
      cities. All together, 36 696 subjects aged between 18 and 98 years were examined.
      In all participants, blood pressure (BP), anthropometric measurements, laboratory
      tests and questionnaire interviews were performed. The social arm of P400CP is
      one of multi-level educational intervention. Modern techniques of social
      psychology and marketing were involved to increase participation in
      interventions. RESULTS: Only 12.5% of all subjects had normal BP, cholesterol
      (<190 mg/dl) and glucose (<100 mg/dl in whole capillary blood) levels. During the
      first screening visit 65.5% of all examined subjects had BP>/=140 mmHg or >/=90
      mmHg. The fasting glucose level was increased in 19% of women and 26% of men.
      Almost two-third of all subjects had a total cholesterol level above the norm.
      CONCLUSIONS: The prevalence of cardiovascular risk factors in participants of the
      screening programme P400CP in small towns in Poland was very high. High
      prevalence and low control of risk factors in participants of the P400CP confirm
      the decision to target this programme at citizens of small towns and villages.

PMID- 17001227
TI  - Factors impeding the implementation of cardiovascular prevention guidelines:
      findings from a survey conducted by the European Society of Cardiology.
AB  - BACKGROUND: Cardiovascular disease mortality remains high in Europe and many
      patients have elevated risk factors, despite evidence-based targets and treatment
      guidelines. This survey examined barriers to implementing cardiovascular risk
      reduction guidelines. DESIGN: We conducted a semi-structured market research
      survey of physicians. METHODS: The survey was conducted in six European countries
      among cardiologists and primary care physicians. In total, 67 questions were
      used: 35 had multiple choice answers (prompted) and 32 allowed any answer
      (unprompted). Respondents were working full-time in patient care (>or=3 years
      experience) and were in a position to initiate cardiovascular drug treatment.
      RESULTS: Of the 220 respondents (155 primary care physicians, 65 cardiologists),
      most (85%) based assessment of cardiovascular risk on all risk factors,
      reflecting a global approach to risk, rather than considering risk factors
      individually. A majority (62%) used subjective assessments for establishing
      global risk rather than guidelines or risk calculators. The most common
      unprompted barrier to guideline implementation was patient compliance (36%) and a
      lack of time (23%), and when prompted, the most important was government health
      policy (40%). The most common unprompted suggestion for improving implementation
      were financial opportunities (24%) and clear and easy to use guidelines (23%),
      while when prompted the most important change required was the development of
      simpler guidelines (46%). CONCLUSIONS: Although a majority of physicians are
      aware of the need to look at a combination of cardiovascular disease risk
      factors, less than half use guidelines or risk calculators to determine total
      risk. It is recommended that guidelines need to be simpler and easier to use and
      supplemented with (patient friendly) risk calculators.

PMID- 17001228
TI  - Short-term effects of atmospheric temperature and humidity on morbidity from
      acute coronary syndromes in free of air pollution rural Greece.
AB  - STUDY OBJECTIVE: An evaluation of the effect of ambient temperature on morbidity
      from acute coronary syndromes (ACS) while avoiding confounding by air pollution.
      DESIGN: An ecological study in rural Greece. METHODS: Daily admissions to
      hospital because of ACS were recorded for 1 year and analysed versus daily
      temperature and humidity. RESULTS: For a 1 degrees C decrease in temperature
      there was a 1.6% (95% confidence interval 0.9-2.2%) increase in admissions. This
      effect was more prominent in the elderly. No difference was detected according to
      sex or type of ACS. CONCLUSION: It is important to implement measures against
      cold in coronary heart disease prevention, irrespective of air pollution.

PMID- 17001229
TI  - Urban air pollution increases plasma fibrinogen and plasminogen activator
      inhibitor-1 levels in susceptible patients.
AB  - BACKGROUND: The cardiovascular effects on fibrinolytic activity by urban air
      pollution are still unknown. METHODS: Paired fasting blood samples during high
      and low air pollution days in Taipei were taken from a panel of 49 patients with
      coronary heart disease or multiple risk factors to study their fibrinolytic and
      inflammatory response to urban air pollution. Paired t-tests and mixed-effects
      models were used to determine the air pollution effects. RESULTS: Patients'
      plasma plasminogen activator inhibitor-1 levels were significantly increased when
      hourly concentrations of particulate matter with diameters less than 10 microm
      (PM10) were greater than 100 microg/m during the period 0800 to 1800 h.
      CONCLUSION: Urban air pollution has an adverse effect on plasma fibrinolytic
      function in a susceptible population.

PMID- 17001231
TI  - Moderate or vigorous exercise? Which best helps prolong life?

PMID- 17001232
TI  - Left ventricular remodelling in outflow tract obstructive lesions during fetal
      life.
AB  - OBJECTIVE: Left ventricular (LV) remodelling in prenatally diagnosed LV outflow
      tract obstructive lesions such as aortic stenosis and aortic coarctation is
      important for prenatal counselling and postnatal management. The purpose of this
      study was to document the spectrum and the progression of different LV
      remodelling patterns and to identify prenatal markers of hypoplastic left heart
      syndrome (HLHS). METHODS: We studied 29 fetuses with LV outflow tract
      obstruction: 13 with isolated aortic stenosis, 14 with isolated aortic
      coarctation and two with combined aortic stenosis and aortic coarctation.
      Echocardiographic evaluation was performed 4 and 8 weeks after the first
      observation and at birth. RESULTS: None of the fetuses had HLHS (LV end-diastolic
      diameter z score higher than -2) at first prenatal echocardiography (24.5 + or -
      3.6 weeks). Fetuses were divided into two groups: group A (n = 25) with a LV end
      diastolic volume at birth > 20 ml/m(2); group B (n = 4) with a LV end-diastolic
      volume at birth < 20 ml/m(2) (LV hypoplasia). At first echocardiographic
      evaluation, the two groups showed a significantly different aorta to pulmonary
      ratio (0.44 + or - 0.08 vs. 0.86 + or - 0.14; P < 0.001); other LV
      echocardiographic features were not significantly different. The growth of the
      mitral (0.10 + or - 0.02 vs. 0.43 + or - 0.28 mm/week; P < 0.02) and aortic
      annulus (0.08 + or - 0.01 vs. 0.26 + or - 0.14 mm/week; P < 0.05) was
      significantly slower in group B. CONCLUSIONS: Our data suggest that LV outflow
      tract obstruction can progressively evolve in HLHS during pregnancy. A smaller
      aorta to pulmonary ratio was the only significant difference at initial
      echocardiographic evaluation in the two groups. Moreover, serial
      echocardiographic examinations are necessary to recognize fetuses at risk for
      HLHS caused by a subnormal growth rate of the mitral and aortic annulus.

PMID- 17001233
TI  - Clinical outcome of patients undergoing low aggressive angioplasty combined with
      brachytherapy and short-term dual antiplatelet therapy for in-stent restenosis.
AB  - OBJECTIVE: The impact of vessel injury on the outcome of patients undergoing
      percutaneous coronary intervention combined with brachytherapy for in-stent
      restenosis is under investigation. We report our clinical experience adopting a
      low aggressive balloon angioplasty technique, to limit vessel trauma, associated
      with brachytherapy and short-term dual antiplatelet therapy. METHODS: Forty-nine
      consecutive patients, undergoing percutaneous coronary intervention with
      brachytherapy for symptomatic in-stent restenosis, were prospectively observed
      for a median time of 21 + or - 8 months. Clinical follow-up included anginal
      status, death, myocardial infarction and repeat revascularization; only patients
      with evidence of ischaemia repeated coronary angiography. Low aggressive
      angioplasty consisted in the use of a conventional balloon with a balloon to
      artery ratio < or = 1, avoiding high inflation pressures and the use of other
      devices. Dual antiplatelet therapy was continued for 3-6 months. RESULTS: Early
      angiographic result was good and the need for additional stent implantation was
      low (3.9%). At follow-up, we did not observe death, acute myocardial infarction
      or stent thrombosis, but 10 patients repeated coronary angiography for recurrence
      of ischaemia: disease progression was present in two cases (4.1%). Restenosis
      emerged in the remaining eight patients (16.3%): two cases showed restenosis
      within the target lesion segment, one case within the injured segment, one case
      within the radiated segment, and four cases at the edges. The consequent new
      revascularization was surgical in three patients and percutaneous in seven
      patients. CONCLUSIONS: Our data suggest that low aggressive angioplasty followed
      by brachytherapy and short-term dual antiplatelet therapy for in-stent restenosis
      is related to a good outcome, with a low restenosis rate and without stent
      thrombosis.

PMID- 17001234
TI  - Contrast-induced nephropathy in urgent coronary interventions.
AB  - OBJECTIVES: Patients submitted to urgent percutaneous coronary interventions
      (PCIs) are quite often at high risk for contrast-induced nephropathy (CIN) since
      they exhibit several predisposing factors such as electrical and haemodynamic
      instability together with the lack of time to undergo adequate prophylaxis. This
      was a not blinded, non-randomized study whose aims were (i) to evaluate the
      incidence of CIN after urgent PCI in a high-volume cardiovascular referral
      practice (patients with acute myocardial infarction or with acute coronary
      syndromes enrolled in a single centre), and (ii) to assess the prognostic
      implications of CIN during hospitalization and at 1-month follow-up. METHODS:
      Between 1 October 2003 and 1 April 2004, 194 consecutive patients undergoing
      urgent coronary angiography and PCIs at our catheterization laboratory were
      enrolled in the study: 67 patients (34.5%) received the iso-osmolar contrast
      medium iodixanol (group A) and 127 patients (65.5%) received the hypo-osmolar
      contrast medium iopromid (group B). RESULTS: The overall incidence of CIN was
      10.82%. Patients of group A showed a higher incidence of CIN than patients of
      group B (22.3 vs. 4.7%, P < 0.05). On univariate logistic analysis, age, pre
      existing renal insufficiency, intra-aortic balloon pump (an indirect indicator of
      haemodynamic instability), dyslipidaemia, and postprocedural hypotension were
      risk indicators for the development of CIN after primary PCI. On multivariate
      logistic analysis, age and postprocedural hypotension remained significant
      independent correlates of CIN. CONCLUSIONS: In emergency PCIs, CIN is a frequent
      complication mainly related to haemodynamic instability and pre-existing renal
      dysfunction. Since CIN is associated with a high in-hospital mortality rate, our
      data stress the need for the development and validation of new preventive
      strategies for renal protection during emergency PCIs.

PMID- 17001235
TI  - Detection of increased left ventricular filling pressure by pulsed tissue Doppler
      in cardiac amyloidosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the incremental diagnostic role
      of tissue Doppler in primary cardiac amyloidosis (CA). METHODS: Eleven patients
      with CA at diagnosis and 11 healthy controls, matched for sex and age, underwent
      standard Doppler echocardiography and pulsed tissue Doppler of the left
      ventricular (LV) lateral annulus, in the apical four-chamber view. The ratio of
      early transmitral flow velocity to early diastolic mitral annular velocity
      (E/E(m) ratio) was derived as an index of LV filling pressure. RESULTS: The two
      groups were comparable for body mass index, blood pressure, heart rate and
      standard Doppler diastolic measurements. Patients with CA had a significantly
      higher sum of wall thickness (SWT) and LV mass, a lower E(m) peak velocity (P <
      0.002) and a higher E/E(m) ratio (P < 0.001) than controls. By dividing CA
      patients according to the transmitral E/A ratio, patients with an E/A ratio < 1
      (abnormal relaxation) (n = 5) and patients with an E/A ratio > 1 (likely
      pseudonormal/restrictive pattern) (n = 6) did not show any difference in the
      E/E(m) ratio (14.5 + or - 7.1 vs. 15.1 + or - 6.4, P = NS). In the overall
      population, the E/E(m) ratio was related to SWT (r = 0.84, P < 0.0001) and LV
      mass index (r = 0.72, P < 0.0001). After adjusting for age and heart rate by
      separate multivariate models, SWT (beta = 0.78, P < 0.0001; cumulative r(2) =
      0.63, SE = 3.38, P < 0.0001) and LV mass index (beta = 0.71, P < 0.0001;
      cumulative r(2) = 0.53, SE = 3.80, P < 0.002) were both independently associated
      with the E/E(m) ratio. CONCLUSIONS: Pulsed tissue Doppler is able to detect early
      myocardial diastolic impairment in CA. The E/E(m) ratio is very useful in
      diagnosing increased LV filling pressure, regardless of the transmitral pattern,
      and may, therefore, be helpful in the clinical management of these patients.

PMID- 17001236
TI  - Transoesophageal echocardiographic evaluation of pulmonary vein anatomy in
      patients undergoing ostial radiofrequency catheter ablation for atrial
      fibrillation: a comparison with magnetic resonance angiography.
AB  - OBJECTIVE: A detailed definition of pulmonary vein (PV) anatomy is of great
      importance in patients undergoing radiofrequency catheter ablation for atrial
      fibrillation. In fact, it is known that variations in the number and anatomy of
      the PV ostia are more frequent than thought. The aim of this study was to assess
      the usefulness of transoesophageal echocardiography (TOE) in defining the exact
      PV anatomy by comparing it with magnetic resonance angiography (MRA), which is
      proven to be very accurate. METHODS: Forty-five consecutive patients (39 male, 6
      female, mean age 50 + or - 6 years) affected by drug-refractory atrial
      fibrillation underwent radiofrequency catheter ablation. They were all studied
      with MRA and then with TOE in order to exclude intra-atrial thrombi and to assess
      PV anatomy. RESULTS: TOE visualised the superior PVs in 100% of cases and the
      right and left inferior PVs in 98% and 94% of cases, respectively. Only 19
      patients (42%) showed typical PV anatomy, with two left and two right distinct PV
      ostia. In 14 patients (31%), one or two intermediate right PVs and in 12 patients
      (27%) a common left trunk were detected. The concordance with MRA was high (95%).
      CONCLUSIONS: TOE is accurate in assessing PV anatomy and in showing anatomic
      variations in the PV ostia compared with MRA. Anomalous pulmonary venous drainage
      is more frequent than expected. TOE can provide functional Doppler information,
      thus being particularly useful in the follow-up after radiofrequency catheter
      ablation.

PMID- 17001237
TI  - Coronary flow velocity pattern assessed by transthoracic Doppler echocardiography
      predicts adverse clinical events and myocardial recovery after successful primary
      angioplasty.
AB  - BACKGROUND: Doppler guidewire studies demonstrated that specific velocity
      patterns in the left anterior descending coronary artery (LAD) after primary
      percutaneous coronary intervention (PCI) predict myocardial recovery and clinical
      outcome. The present study assessed whether similar results can be achieved by
      transthoracic Doppler echocardiography (TTDE). METHODS: Coronary flow velocities
      of LAD were evaluated by TTDE in 35 consecutive patients with anterior acute
      myocardial infarction who were treated with successful primary PCI plus stenting,
      performed within 6 h after the onset of symptoms or within 6-12 h if there was
      evidence of continuing ischaemia. Coronary-flow velocity of the LAD was achieved
      after 12 h and within 48 h after the PCI; TTDE standard examination was repeated
      after 2 months of follow-up. RESULTS: Three patterns were found: (i) 'pattern A'
      with good antegrade systolic flow and slow diastolic deceleration rate (63.7%);
      (ii) 'pattern B' with reduced or absent systolic flow and rapid diastolic
      deceleration rate (9.1%); and (iii) 'pattern C' with protosystolic retrograde
      flow and rapid diastolic deceleration rate (27.2%). The clinical characteristics
      and echocardiographic data were compared: wall-motion-score-index (WMSI),
      ejection fraction, end-diastolic volume (EDV) after PCI (T1) and after 2 months
      (T2). Patients with pattern A demonstrated recovery of contractile function (WMSI
      T1 1.48 + or - 0.42/WMSI-T2 1.29 + or - 0.29, P < 0.05) and better clinical
      outcome; patients with patterns B and C ran into ventricular remodelling (EDV-T1
      89 + or - 6.3 ml/EDV-T2 123 + or - 25 ml, P = 0.002) and more early and late
      complications. CONCLUSIONS: TTDE is a reliable method to achieve coronary flow
      velocities in LAD after an anterior acute myocardial infarction and it could be
      useful to evaluate no-reflow phenomenon at bedside and thus clinical outcome.

PMID- 17001238
TI  - Operator volume and outcomes of primary angioplasty for acute myocardial
      infarction in a single high-volume centre.
AB  - OBJECTIVE: The guidelines for the management of ST-elevation myocardial
      infarction (STEMI) state the minimum operator volume for percutaneous coronary
      interventions (PCIs), without strong evidence of a relationship between operator
      volume and outcomes of primary angioplasty, at variance with elective practice.
      We sought to investigate the effect of operator volume on primary PCI for STEMI.
      METHODS: Three hundred and thirty-one consecutive STEMI patients were treated
      over 19 months with primary PCI in a high-volume centre without on-site cardiac
      surgery. Three skilled operators, with very different volumes of interventional
      practice, performed the PCI procedures around-the-clock. RESULTS: Operators were
      divided into very high (A), intermediate high (B) and low high volume (C).
      Demographic, clinical, angiographic, and procedural characteristics of the
      patient population did not differ among operators, with the exception of three
      vessel disease (P = 0.016), circumflex infarct-related artery (P = 0.002),
      mechanical support (P = 0.02), use of abciximab (P = 0.003) for operator C, use
      of tirofiban for operator B (P = 0.02), and type of stent for operator A (P =
      0.0004). Similarly, no differences were observed among operators in in-hospital
      outcomes (death, a composite of major adverse cardiovascular events, ST-segment
      resolution, thrombolysis in myocardial infarction flow grade 3, length of
      hospitalization) and haemorrhagic complications. CONCLUSIONS: Our data show that
      there is not a significant relationship between operator volume over the
      threshold indicated by the guidelines, and both primary PCI early outcomes and
      complications in STEMI, and suggest that expertise and experience of the whole
      professional team rather than just of the individual operator play a major role.

PMID- 17001239
TI  - Unusual location in the left ventricular outflow tract and atypical symptoms of
      cardiac papillary fibroelastoma.
AB  - Cardiac papillary fibroelastoma, though potentially fatal, are rare benign
      tumours. Therefore, high index of suspicion is needed in order to identify these
      lesions and to limit complications at surgery or during long-term oral
      anticoagulation if the patient is not a surgical candidate. We present a case
      report of unusual location and presentation, highlighting the pathological
      findings. A 55-year-old white male, without risk factors for ischaemic
      cardiomyopathy, presented several episodes of chest pain. Nine years previously,
      the patient had had a convulsive attack without any organic neurological finding
      and was treated with different anticonvulsive drugs for five years.
      Echocardiography showed a mobile mass in the left ventricular outflow tract. The
      patient underwent surgical excision of the mass, which was later identified as
      cardiac papillary fibroelastoma.

PMID- 17001240
TI  - Very late thrombosis of a drug-eluting stent deployed during primary angioplasty
      for ST-elevation myocardial infarction.
AB  - Drug-eluting stents, despite being very effective in reducing restenosis after
      percutaneous coronary interventions, are associated with a low but definite risk
      of late thrombotic occlusion with adverse clinical events. To date, the incidence
      and overall risk of late thrombosis of drug-eluting stents after primary
      percutaneous coronary interventions for ST-elevation myocardial infarction are
      not well defined because of the relative paucity of evidence-based data. We
      report the case of an angiographically confirmed paclitaxel-eluting stent
      thrombosis, occurring 20 months after successful primary percutaneous coronary
      intervention in a 41-year-old woman. To the best of our knowledge, this is the
      most delayed case of paclitaxel-eluting stent thrombosis described so far.

PMID- 17001241
TI  - Transcatheter treatment of perimembranous ventricular septal defect, secundum
      atrial septal defect and patent ductus arteriosus in a child.
AB  - A 4-year-old child with patent ductus arteriosus, perimembranous ventricular
      septal defect and ostium secundum atrial septal defect was successfully treated
      with the use of a simultaneous transcatheter for all of the anomalies present.
      The patent ductus arteriosus was closed first by using a coil, then the
      perimembranous ventricular septal defect was closed by using a 10-mm Amplatzer
      eccentric device. Finally, a 10-mm Amplatzer atrial septal defect device was
      implanted to treat the atrial septal defect.

PMID- 17001242
TI  - Left ventricular pseudoaneurysm protruding outside the chest wall.

PMID- 17001243
TI  - Correction of deformities in children using the Taylor spatial frame.
AB  - The Taylor spatial frame is a unique external fixator. Despite its growing
      popularity, few reports on its use have been published. We evaluated the
      effectiveness of the Taylor spatial frame in the treatment of various deformities
      in 31 children and adolescents. All but one patient were anatomically corrected.
      Complications included superficial pin tract infection (45%), three fractures of
      the femoral regenerate, transient peroneal palsy, and injury to the genicular
      artery. Despite many challenging problems, our results compared favorably with
      the results achieved by others. We believe that the Taylor spatial frame is a
      very capable and accurate fixator for the precise correction of complex
      deformities.

PMID- 17001244
TI  - Percutaneous osteotomy for deformity correction in adolescents with severe
      slipped capital femoral epiphysis.
AB  - Various methods of performing proximal femoral realignment in adolescents with
      severe slipped capital femoral epiphysis exist. We report the technique and early
      results of a percutaneous, opening wedge subtrochanteric femoral osteotomy using
      an external fixator for correcting multiplanar deformities in such patients. Nine
      adolescents with severe slipped capital femoral epiphysis underwent a
      percutaneous osteotomy at an average age of 14.5 years. Mean operative blood loss
      was 61 ml, with 2 days of inpatient stay and 129 days of external fixation time.
      At an average follow-up of 23 months, hip flexion improved from 74 to 106
      degrees, internal rotation from -5 to +17 degrees, external rotation from 71 to
      41 degrees and abduction from 29 to 36 degrees. Radiographs revealed an
      improvement in anteroposterior head shaft angle from 112 to 134 degrees and
      lateral head shaft angle from 72 to 15 degrees. One patient had transient
      chondrolysis. No fixation-related problems, deep infection, avascular necrosis or
      refracture occurred. On the basis of our preliminary results, this percutaneous
      technique offers several advantages over currently available methods for surgical
      correction of severe slipped capital femoral epiphysis deformities.

PMID- 17001245
TI  - Predicting the loss of knee flexion during limb lengthening using inherent muscle
      length.
AB  - Limb lengthening procedures can be associated with loss of range of knee
      movement, although the amount of knee flexion lost varies markedly between
      patients. The exact aetiology of this problem is not fully understood. This study
      investigates whether the amount of joint range that is lost during limb
      lengthening might be affected by the inherent passive compliance and length of
      the patients' soft tissues determined preoperatively. A simple mathematical model
      has been developed to calculate the inherent length and 'spare' length of the
      hamstring and quadriceps muscle groups in 28 patients undergoing limb lengthening
      procedures. The range of knee motion was recorded preoperatively and loss of
      movement recorded during follow-up. The results show a strong correlation between
      predicted 'spare' length of quadriceps and loss of knee flexion. An association
      was noted between loss of knee extension and the straight leg raise and
      correlation of knee extension and the spare length of the hamstrings. The
      straight leg raise test, and calculation of spare quadriceps length using our
      formula, as part of the preoperative assessment, can help predict which patient
      is at risk of a reduced range of motion of the knee.

PMID- 17001246
TI  - Complications associated with multiple, sequential osteotomies for children with
      cerebral palsy.
AB  - Children with cerebral palsy often require multiple, major reconstructive
      procedures. The purpose of this study was to evaluate whether multiple, major
      surgeries could be performed in a single setting with an acceptable complication
      rate. The medical records of 94 patients with a diagnosis of cerebral palsy
      operated on between the dates of 1993 and 1997 were reviewed. Patients were
      followed for a mean of 44.9+/-1.92 months. The average number of procedures per
      surgical session was 3.63+/-0.09 and the most common procedure performed was
      osteotomy of the proximal femur. The major complication rate was 24.4%. This
      institution's experience indicates that performance of multiple major bony
      procedures in one session is complicated but safe, and can be done with
      acceptable blood loss, infection rates and recurrence rates in a modern,
      multidisciplinary setting dedicated to the care of severely disabled children.

PMID- 17001247
TI  - Botulinum toxin injection site localization for the tibialis posterior muscle.
AB  - Thirty-one cadaveric lower limbs were dissected to identify the innervation of
      the tibialis posterior muscle to aid localization of the injection site for
      botulinum toxin for the treatment of an equinovarus deformity. A posterior
      midline surface-anatomy axis was defined from the level of the head of the fibula
      proximally to the intermalleolar axis distally. The nerve to tibialis posterior
      branched from the tibial trunk 13.4% down this axis and entered the muscle 22.1%
      along the same axis, within 1 cm of the midline. We also report the use of
      ultrasound for muscle localization at the level of the anatomically defined motor
      point.

PMID- 17001248
TI  - The role of ultrasound in differentiating septic arthritis from transient
      synovitis of the hip in children.
AB  - A total of 154 children admitted with septic arthritis (n=81) or transient
      synovitis (n=73) were studied retrospectively. Ultrasound findings for 127
      patients were correlated with the final diagnosis. Sensitivity, specificity and
      positive predictive value of ultrasound for the diagnosis of pediatric septic hip
      were 86.4, 89.7 and 87.9%, respectively. Unsatisfactory outcome occurred more
      significantly in children, for whom treatment was initiated more than 4 days
      after the onset of symptoms and those who had a false-negative ultrasound study.
      Ultrasound cannot be used safely to distinguish between pediatric septic hip and
      transient synovitis. It may be a method of value to detect minimal hip effusion.
      A predictive algorithm using clinical, laboratory and ultrasound findings could
      be beneficial.

PMID- 17001249
TI  - Case report: biceps tenosynovial rice bodies.
AB  - Here we report the first documented case of rice body formation within the biceps
      tenosynovium in a patient with juvenile rheumatoid arthritis. We discuss the
      pathophysiology and the clinical and radiographic findings and correlate these to
      prior case studies. Lastly, we suggest that limited awareness is a barrier in
      achieving a timely diagnosis and appropriate management.

PMID- 17001250
TI  - Key pinch force in children.
AB  - The key pinch force in a group of 262 healthy children between 5 and 12 years was
      measured. A clear correlation was observed between age and key pinch strength.
      The differences between the left and right hand grips and between girls and boys
      were not significant.

PMID- 17001251
TI  - Acceptance of angulation in the non-operative treatment of paediatric forearm
      fractures.
AB  - Forearm fractures are the most common injury in paediatric traumatology. The
      unique properties of the juvenile skeleton make it possible to cope well with
      traumatic deformities such as angulation, apposition and displacement. While we
      make use of these properties, the exact mechanism and degree of healing remains
      obscure. Different types of forearm fractures require specific treatment options,
      each with its limitations. A meta-analysis of recent literature was carried out,
      and together with the opinions of 18 international experts an effort was made to
      provide insight into the limits of acceptance of angular deformation in the non
      operative treatment of paediatric forearm fractures. With this information we
      constructed graphs (age versus angulation) for each of the eight types of
      paediatric forearm fractures. In the absence of proper trials, it is our opinion
      that the presented Isala graphs can provide useful support in the decision-making
      process of acceptance of angular deformities in paediatric forearm fractures.

PMID- 17001252
TI  - Long-term prognosis of Salter-Harris type 2 injuries of the distal femoral
      physis.
AB  - The objective of this study was to assess long-term sequelae of Salter-Harris
      type 2 injuries on growth of the distal femoral physis. A retrospective study of
      20 patients with Salter-Harris type 2 distal femoral injuries, who were managed
      between 1994 and 2003, was carried out. The average period of follow-up was 4
      years and 2 months. Mean age of fracture was 11 years (range 8-15 years). We
      classified radiologically these fractures into three types according to initial
      displacement on anteroposterior and lateral radiographs (type 1=less than 2 mm;
      type 2=more than 2 mm, contact between fragments; type 3=no contact). Further
      subdivision into A and B was made according to the absence or presence of
      metaphyseal comminution. Clinical and radiological outcomes were evaluated at
      latest follow-up. Two patients with type 1 injuries were treated conservatively,
      with no complication. All type 2 and 3 fractures (18) were reduced under general
      anesthesia. At latest follow-up, 14 patients (70%) sustained a complication due
      to either epiphysiodesis (12), femoral over-lengthening (1) or associated loss of
      knee motion (5). Seven out of the 12 epiphysiodeses were initial type B injuries.
      All type 3 fractures ended with complications. The prognosis of these fractures,
      often caused by a high-energy trauma, can be severe. Additional subdivision of
      Salter-Harris type 2 distal femoral physeal injuries is proposed to warn the
      clinician on specific fracture patterns with higher complication risk. Greater
      awareness of the numerous growth problems that may occur is needed in type 2B, in
      which the germinal layer of the physeal cells is damaged.

PMID- 17001253
TI  - Subtrochanteric femoral fractures due to simple bone cysts in children.
AB  - Seven children were treated surgically as a result of a pathologic fracture
      through a simple bone cyst in the subtrochanteric region of the proximal femur.
      Average age at surgery was 10.6 years. Six children were treated primarily. One
      child was operated for a refracture through a persistent cyst and malunion of a
      previous fracture that had been treated nonoperatively. Surgery included
      curettage of cysts in all patients. The cysts were filled with autologous bone
      graft in five patients and Osteoset bone substitute in two patients. The fracture
      was stabilized using a blade plate in three patients, a screw and side plate in
      three patients and an external fixator in one. At average follow-up of 4.7 years,
      all fractures had healed uneventfully. The cyst was fully obliterated in five
      patients and partially obliterated in two patients. One patient had a relative
      lengthening of 2 cm on the affected side. All patients were asymptomatic, fully
      active and had full range of motion.

PMID- 17001254
TI  - Measurement of tissue hardness: can this be a method of diagnosing compartment
      syndrome noninvasively in children?
AB  - In order to assess the feasibility of using the measurement of tissue hardness as
      a method of diagnosing compartment syndrome noninvasively in children, a simple
      hand-held device to measure tissue hardness was fabricated. The relationship
      between hardness and compartmental pressure was studied in an experimental model
      and in three fresh amputated lower limbs. Normal tissue hardness of the forearm
      was measured in 189 children and 20 adults to identify the factors that influence
      normal tissue hardness. The reproducibility of measurement of tissue hardness was
      assessed on the experimental model, on the amputated limbs and in normal
      individuals. Experimental data from this study suggest that there is a nonlinear
      relationship between intracompartmental pressure and tissue hardness. The study
      also shows that tissue hardness can be measured reproducibly in the forearm of
      children with the device. Several factors influence tissue hardness such as the
      age of the child, the site of measurement on the limb, the hand dominance and
      active muscle contraction. These factors may affect the specificity of this
      measure as a screening tool for diagnosing compartment syndrome. Further
      refinement of the measuring device and well designed clinical trials are needed
      to establish whether compartmental syndrome can be diagnosed reliably by
      measuring tissue hardness noninvasively.

PMID- 17001255
TI  - Focal fibrocartilaginous dysplasia in the humerus.
AB  - Focal fibrocartilaginous dysplasia is an uncommon, benign bone lesion that causes
      deformity of the long bones in young children. It has most commonly been
      encountered in the proximal tibia, and very rarely in the long bones of the upper
      limb, that is, the proximal humerus, distal radius, ulna and proximal phalanx.
      Only one case of focal fibrocartilaginous dysplasia of the proximal humerus has
      been reported previously. The present study reports two such additional cases
      that were diagnosed in late childhood. The clinical presentation and radiographic
      findings are described with an emphasis on the natural evolution of the disease.
      Limb-length discrepancy is anticipated in these children in the long-term follow
      up and, therefore, surgical intervention should be considered in treatment.

PMID- 17001256
TI  - Radial dysplasia with localized cutis aplasia congenita.

PMID- 17001258
TI  - The value and challenges of improving adherence to antiretroviral therapy for
      human immunodeficiency virus.

PMID- 17001259
TI  - Clinical and economic outcomes of nonadherence to highly active antiretroviral
      therapy in patients with human immunodeficiency virus.
AB  - BACKGROUND: Nonadherence with highly active antiretroviral therapy (HAART) is
      common in typical human immunodeficiency virus (HIV) patient care settings, but
      the consequences have not been well described. This study aimed to quantify the
      clinical and economic effects of nonadherence and estimate the cost-effectiveness
      of improving adherence in treatment-naive HIV patients. METHODS: A Markov model
      was developed to project quality-adjusted life expectancy and direct medical
      costs for patients on an initial once-daily regimen of efavirenz, lamivudine, and
      stavudine XR. The model compared 2 adherence scenarios: "ideal" (based on
      clinical trials) and "typical" (based on observational studies in actual
      practice). Disease progression was a function of viral load, CD4 count, and
      adherence. Data on HIV natural history, treatment benefits, costs, and utilities
      were derived from the literature. RESULTS: With typical adherence, patients lose
      1.2 quality-adjusted life years (QALYs) that could be gained with ideal
      adherence. Improving adherence to ideal levels is cost-effective at 29,400 US
      dollars/QALY gained. As much as 1,600 US dollars/y per patient could be spent on
      an intervention to improve adherence to ideal levels, and the incremental cost
      effectiveness would remain less than 50,000 US dollars/QALY gained. A cost
      effectiveness ratio of 50,000 US dollars/QALY is a commonly accepted minimum
      standard for cost-effective medical interventions in the United States, although
      many experts believe this standard has drifted upwards over time. CONCLUSIONS:
      Typical adherence with HAART reduces quality-adjusted life expectancy by 12%
      compared with ideal adherence. Interventions to improve adherence appear to be a
      highly cost-effective use of resources.

PMID- 17001260
TI  - The effect of medicare health maintenance organizations on hospitalization rates
      for ambulatory care-sensitive conditions.
AB  - OBJECTIVE: The objective of this study was to estimate the effect of Medicare
      Health Maintenance Organization (HMO) enrollment on hospitalization rates and
      total inpatient days for ambulatory care-sensitive conditions (ACSCs) after
      controlling for selection. RESEARCH DESIGN: Simultaneous equations using a
      discrete factor selection model are used to estimate the probability of HMO
      enrollment, hospitalization rates, and total inpatient days for ACSCs. SUBJECTS:
      Enrollment data on Medicare beneficiaries in California were linked to hospital
      discharge data from the California Office of Statewide Health Planning and
      Development for January through December 1996. The following beneficiaries were
      excluded: 1) end-stage renal disease, 2) under 65 years of age, 3) not covered by
      both Medicare Part A and Part B, 4) switched between HMOs and fee-for-service
      (FFS), and 5) switched between HMOs. The sample was stratified by age, gender,
      race, county, disability, Medicaid eligibility, HMO status, and death. A 2%
      random sample from the 4 California counties with the largest Medicare enrollment
      yielded 10,448 HMO enrollees and 11,803 FFS beneficiaries. RESULTS: Using a
      discrete factor selection model, we estimated the rate of ACSC hospitalizations
      among FFS beneficiaries would decline from 51.2 to 44.2 per 1000 if all FFS
      beneficiaries joined an HMO. Similarly, the mean total inpatient days for ACSC
      hospitalizations would be reduced from 7.5 days to 5.1 days if all FFS
      beneficiaries joined an HMO. CONCLUSIONS: After controlling for selection,
      Medicare HMO enrollees have lower hospitalization rates and fewer total inpatient
      days for 15 ACSCs than Medicare FFS beneficiaries. These findings suggest
      selection of healthier beneficiaries into HMOs does not completely explain their
      lower rates of ACSC hospitalization.

PMID- 17001261
TI  - The impact of seeing physicians new to a patient on the response to screening
      reminders.
AB  - BACKGROUND: A large insurer in Hawaii mails annual reminders to its members
      regarding recommended health screenings. This study examined the associations
      between the characteristics of physicians visited after the reminders were sent
      and the health screenings received for breast, cervical, and colorectal cancers,
      and for diabetes and cholesterol. METHODS: The study population included members
      identified as needing health screenings from 2000 to 2003 based on age and gender
      criteria. The study used a longitudinal design focusing on the 12 months after
      reminders were sent. Data were analyzed using logistic regression examining
      physician visits, other health services, and receipt of health screenings by 1
      month intervals subsequent to the reminder mailings. RESULTS: In adjusted,
      multivariable models, members who saw physicians they had not seen in the past
      year had odds ratios for obtaining health screenings 6 to 8 times higher than
      members who only saw previously visited physicians. This enhanced response
      occurred among members receiving their first, second, and third (or subsequent)
      annual reminder letter. The more physicians that were visited and who were new to
      the members, the more likely the members were to obtain health screenings.
      CONCLUSIONS: Members seeing physicians they had not seen in the past year had
      significantly higher screening rates than the members only seeing physicians they
      had previously visited. The results suggest that healthcare screening may receive
      less attention at repeat visits with a physician than at visits with a physician
      who is new to a member.

PMID- 17001262
TI  - Immigrant perceptions of discrimination in health care: the California Health
      Interview Survey 2003.
AB  - BACKGROUND: U.S. healthcare disparities may be in part the result of differential
      experiences of discrimination in health care. Previous research about
      discrimination has focused on race/ethnicity. Because immigrants are clustered in
      certain racial and ethnic groups, failure to consider immigration status could
      distort race/ethnicity effects. OBJECTIVES: We examined whether foreign-born
      persons are more likely to report discrimination in healthcare than U.S.-born
      persons in the same race/ethnic group, whether the immigration effect varies by
      race/ethnicity, and whether the immigration effect is "explained" by
      sociodemographic factors. RESEARCH DESIGN: The authors conducted a cross
      sectional analysis of the 2003 California Health Interview Survey consisting of
      42,044 adult respondents. Logistic regression models use replicate weights to
      adjust for nonresponse and complex survey design. OUTCOME MEASURE: The outcome
      measure of this study was respondent reports that there was a time when they
      would have gotten better medical care if they had belonged to a different race or
      ethnic group. RESULTS: Seven percent of blacks and Latinos and 4% of Asians
      reported healthcare discrimination within the past 5 years. Immigrants were more
      likely to report discrimination than U.S.-born persons adjusting for
      race/ethnicity. For Asians, only the foreign-born were more likely than whites to
      report discrimination. For Latinos, increased perceptions of discrimination were
      attributable to sociodemographic factors for the U.S.-born but not for the
      foreign-born. Speaking a language other than English at home increased
      discrimination reports regardless of birthplace; private insurance was protective
      for the U.S.-born only. CONCLUSIONS: Immigration status should be included in
      studies of healthcare disparities because nativity is a key determinant of
      discrimination experiences for Asians and Latinos.

PMID- 17001263
TI  - Data sources for measuring comorbidity: a comparison of hospital records and
      medicare claims for cancer patients.
AB  - BACKGROUND: Identifying appropriate comorbidity data sources is a key
      consideration in health services and outcomes research. OBJECTIVE: Using cancer
      patients as an example, we compared comorbid conditions identified: 1) on the
      discharge facesheet versus full hospital medical record and 2) in the hospital
      record versus Medicare claims, both precancer diagnosis and associated with a
      cancer treatment-related index hospitalization. METHODS: We used data from 1995
      Surveillance, Epidemiology and End Results patterns of care studies for 1,382
      patients. Comorbid conditions were ascertained from the hospital record
      associated with the most definitive cancer treatment and Medicare claims. We
      calculated the prevalence for and assessed concordances among 12 conditions
      derived from the hospital record facesheet; full hospital record; Medicare claims
      precancer diagnosis, with and without a rule-out algorithm applied; and Medicare
      claims associated with an index hospitalization. RESULTS: The proportion of
      patients with one or more comorbid conditions varied by data source, from 21% for
      the facesheet to 85% for prediagnosis Medicare claims without the rule-out
      algorithm. Condition prevalences were substantially lower for the facesheet
      compared with the full hospital record. For prediagnosis Medicare claims,
      condition prevalences were more than 1.7 times greater in the absence of an
      algorithm to screen for rule-out diagnoses. Measures assessing concordance
      between the full hospital record and prediagnosis Medicare claims (rule-out
      algorithm applied) showed modest agreement. CONCLUSIONS: The hospital record and
      Medicare claims are complementary data sources for identifying comorbid
      conditions. Comorbidity is greatly underascertained when derived only from the
      facesheet of the hospital record. Investigators using Part B Medicare claims to
      measure comorbidity should remove conditions that are listed for purposes of
      generating bills but are not true comorbidities.

PMID- 17001264
TI  - Care outcomes in long-term care facilities in British Columbia, Canada. Does
      ownership matter?
AB  - OBJECTIVES: This study investigated whether for-profit (FP) versus not-for-profit
      (NP) ownership of long-term care facilities resulted in a difference in hospital
      admission and mortality rates among facility residents in British Columbia,
      Canada. RESEARCH DESIGN: This retrospective cohort study used administrative data
      on all residents of British Columbia long-term care facilities between April 1,
      1996, and August 1, 1999 (n = 43,065). Hospitalizations were examined for 6
      diagnoses (falls, pneumonia, anemia, dehydration, urinary tract infection, and
      decubitus ulcers and/or gangrene), which are considered to be reflective of
      facility quality of care. In addition to FP versus NP status, facilities were
      divided into ownership subgroups to investigate outcomes by differences in
      governance and operational structures. RESULTS: We found that, overall, FP
      facilities demonstrated higher adjusted hospitalization rates for pneumonia,
      anemia, and dehydration and no difference for falls, urinary tract infections, or
      DCU/gangrene. FP facilities demonstrated higher adjusted hospitalization rates
      compared with NP facilities attached to a hospital, amalgamated to a regional
      health authority, or that were multisite. This effect was not present when
      comparing FP facilities to NP single-site facilities. There was no difference in
      mortality rates in FP versus NP facilities. CONCLUSIONS: The higher adjusted
      hospitalization rates in FP versus NP facilities is consistent with previous
      research from U.S. authors. However, the superior performance by the NP sector is
      driven by NP-owned facilities connected to a hospital or health authority, or
      that had more than one site of operation.

PMID- 17001265
TI  - The quality of pharmacologic care for adults in the United States.
AB  - BACKGROUND: Despite rising annual expenditures for prescription drugs, little
      systematic information is available concerning the quality of pharmacologic care
      for adults in the United States. We evaluated how frequently appropriate
      pharmacologic care is ordered in a national sample of U.S. residents. METHODS:
      The RAND/UCLA Modified Delphi process was used to select quality-of-care
      indicators for adults across 30 chronic and acute conditions and preventive care.
      One hundred thirty-three pharmacologic quality-of-care indicators were
      identified. We interviewed a random sample of adults living in 12 metropolitan
      areas in the United States by telephone and received consent to obtain copies of
      their medical records for the most recent 2-year period. We abstracted patient
      medical records and evaluated 4 domains of the prescribing process that
      encompassed the entire pharmacologic care experience: appropriate medication
      prescribing (underuse), avoidance of inappropriate medications (overuse),
      medication monitoring, and medication education and documentation. A total of
      3,457 participants were eligible for at least 1 quality indicator, and 10,739
      eligible events were evaluated. We constructed aggregate scores and studied
      whether patient, insurance, and community factors impact quality. RESULTS:
      Participants received 61.9% of recommended pharmacologic care overall (95%
      confidence interval 60.3-63.5%). Performance was lowest in education and
      documentation (46.2%); medication monitoring (54.7%) and underuse of appropriate
      medications (62.6%) performance were higher. Performance was best for avoiding
      inappropriate medications (83.5%). Patient race and health services utilization
      were associated with modest quality differences, while insurance status was not.
      CONCLUSIONS: Significant deficits in the quality of pharmacologic care were seen
      for adults in the United States, with large shortfalls associated with underuse
      of appropriate medications. Strategies to measure and improve pharmacologic care
      quality ought to be considered, especially as we initiate a prescription drug
      benefit for seniors.

PMID- 17001266
TI  - Productivity and turnover in PCPs: the role of staff participation in decision
      making.
AB  - BACKGROUND: Efforts to redesign primary care practices are beginning to address
      how decisions are made in the practice setting. This study contributes to these
      efforts by examining associations between staff participation in decision-making,
      productivity, and turnover in primary care practices. The study is informed by
      organizational theories of participation that emphasize cognitive and affective
      influences on employee output and behavior. METHODS: This research used data
      collected from primary care practices involved in a national initiative sponsored
      by the Robert Wood Johnson Foundation. Cross-sectional survey data on
      organizational structures and attributes among 49 practices were analyzed.
      Regression analysis was used to examine associations among practice productivity,
      staff participation in decision-making, and formal structures such as staff
      meetings. Associations between staff turnover and participative decision-making
      were also examined. RESULTS: Staff participation in decisions regarding quality
      improvement, practice change, and clinical operations was positively associated
      with practice productivity, whereas formal structures such as staff meetings were
      not. In addition, higher levels of participation in decision-making were
      associated with reduced turnover among nonclinicians and administrative staff.
      CONCLUSION: Examination of organizational features is increasingly recognized as
      a key to improving primary care performance. Study findings suggest that one
      important strategy may be implementation of a participative model emphasizing
      greater staff involvement in practice decisions. This may enhance information
      sharing, work satisfaction, and commitment to organizational decisions, all of
      which can lead to beneficial outcomes such as increased productivity and
      stability in primary care practices.

PMID- 17001267
TI  - Validity of cancer registry medicaid status against enrollment files:
      implications for population-based studies of cancer outcomes.
AB  - BACKGROUND: Poor access to or inadequate health insurance contributes to
      disparities in cancer incidence and mortality. Cancer registry "payer source"
      data is collected by many cancer registries in the United States and has been
      used to compare cancer outcomes across insurance types. OBJECTIVES: We evaluated
      the validity of cancer registry data on patient Medicaid status against
      enrollment data from Medi-Cal, California's Medicaid program. METHODS: Data from
      the statewide California Cancer Registry for persons under age 65 years diagnosed
      with 1) any cancer in 1998 and 1999 or 2) with invasive cervical cancer between
      1996 and 1999 were obtained and linked probabilistically to Medi-Cal enrollment
      files. We compared registry Medicaid status, determined from payer source
      information, against linkage results and used crosstabulations to calculate
      sensitivity, specificity, and positive predictive value. These measures were
      compared across different hospital and patient characteristics and cancer types.
      RESULTS: Cancer registry Medicaid status data had poor sensitivity (48%), good
      specificity (98%), and moderate positive predictive value (77%). Measures of
      validity did not vary substantially by cancer type, stage, patient age, sex,
      vital status, race/ethnicity, socioeconomic status, or diagnosing hospital size.
      Registry data undercounted the number of Medicaid patients by 52% and incorrectly
      assigned Medicaid as a payer to approximately 2% of patients. CONCLUSIONS: As a
      result of the poor validity of cancer registry Medicaid status data, caution
      should be used when interpreting cancer outcomes by insurance type calculated
      from registry payer source data. Linkage of registry data to Medicaid enrollment
      files represents a more accurate means of identifying Medicaid insurance status.

PMID- 17001268
TI  - Transforming the SF-36 to account for death in longitudinal studies with three
      year follow-up.
AB  - BACKGROUND: Analyses of longitudinal health-related quality of life data often
      exclude participants who die, which limits the generalizability of the results.
      Methods to incorporate death as a valid score in the Medical Outcomes Study Short
      Form (SF-36) have been suggested but need to be evaluated in other populations.
      OBJECTIVES: We sought to apply a method of transforming the SF-36 Physical
      Component Score (PCS) to include death. A transformation to estimate the
      probability of being "healthy" in 3 years, based on the current PCS value, will
      be developed and validated. SUBJECTS: Women in the Australian Longitudinal Study
      on Women's Health (ALSWH), ages 70-75 years at Survey 1 in 1996 (n = 12,432),
      were followed-up at 3 yearly intervals for 6 years. RESULTS: The transformation
      derived from the ALSWH data provides evidence that the methodology for
      transforming the PCS to account for deaths is sound. The 3-year equation provided
      good estimates of the probability of being healthy in 3 years and the method
      allowed deaths to be included in an analysis of changes in health over time.
      CONCLUSIONS: For longitudinal studies involving the SF-36 in which subjects have
      died, we support the recommendation that both the PCS and its transformed value
      which includes deaths should be analyzed to examine the influence of deaths on
      the study conclusions. Using study data to derive empirical parameters for the
      transformations may be appropriate for studies with follow-up intervals of other
      lengths.

PMID- 17001269
TI  - How finger tapping practice enhances efficiency of motor control.
AB  - Maximum-speed movements have been suggested to put maximum neural control demands
      on the primary motor cortex; hence, we are asking how primary motor cortex
      function changes to enable enhanced maximum movement rates induced by long
      lasting practice. Cortical function was assessed by recording task-related
      spectral electroencephalogram alpha-power. Low-resolution brain electromagnetic
      tomography was used to localize intracortical neuronal sources. The main result
      is a decrease in neural activity in the left hemisphere (ipsilateral to trained
      hand) from pretraining to posttraining, whereas right hemispheric activity
      remained constant across training. This likely reflects the initially limited
      capacity of the right hemisphere to control demanding left-hand movements, but
      also highlights its ability to become more efficient with training, indicated by
      reduced involvement of the left primary motor cortex after training.

PMID- 17001270
TI  - Colour recognition at large visual eccentricities in normal observers and
      patients with low vision.
AB  - When we look at our spatial environment we have the feeling that the whole visual
      field is coloured, yet the density of cone photoreceptors decreases considerably
      as eccentricity increases. We investigated colour perception
      (coloured/noncoloured), colour naming and whether colour helps object recognition
      at eccentricities varying from 0 degrees to 80 degrees in healthy observers and
      patients with low vision. We found that colours can be perceived and even
      identified above chance at very large eccentricities (60 degrees). When asked to
      categorize coloured and grey level objects as edible/nonedible, both healthy
      observers and patients with low vision showed better performance for coloured
      edible objects at 50 degrees suggesting that colour is used for object
      recognition in conditions of degraded form perception.

PMID- 17001271
TI  - Mitogen-activated protein kinase signaling is essential for activity-dependent
      dendritic protein synthesis.
AB  - The expression of long-lasting synaptic plasticity requires synthesis of new
      proteins. A critical locus for protein synthesis to support synaptic plasticity
      is the dendrites. Previous studies demonstrate that synaptic activity activates
      dendritic protein synthesis. The mechanism by which synaptic activity stimulates
      protein synthesis in dendrites is, however, poorly understood. This study is to
      determine the role of the mitogen-activated protein kinase signaling pathway in
      activity-dependent dendritic protein synthesis. Using a green fluorescent protein
      reporter with CaMKII 5' and 3'untranslated regions, we show that dendritic
      synthesis of the green fluorescent protein induced by N-methyl-D-aspartate
      stimulation is abolished by U0126, a specific inhibitor of mitogen-activated
      protein kinase signaling. Our results suggest an important role of the mitogen
      activated protein kinase signaling in dendritic protein synthesis induced by N
      methyl-D-aspartate receptor activation.

PMID- 17001272
TI  - Polyguanosine motif increases cellular oligonucleotide uptake in the brain
      cortex.
AB  - Cellular uptake and localization of fluorescein isothiocyanate-labelled or biotin
      labelled CpG-oligonucleotides (oligonucleotides containing unmethylated CpG
      dinucleotides within specific flanking bases) with or without 3'-end continuous
      guanosines (polyG motif) were studied in the rat cortex. Twenty minutes after
      intracerebral microinjection, labelled CpG-oligonucleotide accumulated in both
      nuclear and cytoplasmic compartments of neuronal and nonneuronal cells localized
      near the injection site. In the brain, polyG motif significantly increased the
      cellular uptake of phosphodiester CpG-oligonucleotide (P < 0.05) but not
      phosphothioate CpG-oligonucleotide (P > 0.05). These data not only provide in
      vivo evidence for the local uptake and distribution of oligonucleotides in the
      brain cortex but also indicate that phosphodiester CpG-oligonucleotides
      containing a 3'-end polyG motif show an increased cellular uptake and thus might
      be promising alternate analogues for application to the brain.

PMID- 17001273
TI  - Functional magnetic resonance imaging and magnetoencephalography differences
      associated with APOEepsilon4 in young healthy adults.
AB  - Functional neural alterations are present in middle-aged to late-aged healthy
      individuals carrying the epsilon4 allele of the apolipoprotein E (APOEepsilon4)
      gene, a known risk factor for Alzheimer's disease. Neural activity was measured
      in young adults with and without the epsilon4 allele (APOEepsilon4+ and
      APOEepsilon4-) by functional magnetic resonance imaging and
      magnetoencephalography while performing a visual working memory task on two
      separate days. Greater activity was observed in frontal areas and cingulate gyri
      in APOEepsilon4+ participants by both functional magnetic resonance imaging and
      magnetoencephalography with regional blood oxygenation level-dependent responses
      correlating with increased theta band power. The findings suggest that the
      presence of the APOEepsilon4 allele has physiological consequences before aging
      that may contribute to risk for Alzheimer's disease.

PMID- 17001274
TI  - Role of the inferior frontal cortex in coping with distracting emotions.
AB  - The role of inferior frontal cortex in coping with emotional distracters
      presented concurrently with a working memory task was investigated using event
      related functional magnetic resonance imaging. The study yielded two main
      findings: (i) processing of emotional distracters was associated with enhanced
      functional coupling between the amygdala and the inferior frontal cortex and (ii)
      the inferior frontal cortex showed a left-lateralized activation pattern
      discriminating successful from unsuccessful trials in the presence of emotional
      distraction. These findings provide evidence that coping with emotional
      distraction entails interactions between brain regions responsible for detection
      and inhibition of emotional distraction, and identified a hemispheric
      specialization in the inferior frontal cortex in controlling the impact of
      distracting emotions on cognitive performance (left hemisphere) vs. controlling
      the subjective feeling of being distracted (right hemisphere).

PMID- 17001275
TI  - Rapid targeting followed by sustained deployment of visual spatial attention.
AB  - We investigated preparatory attention processes when a spatial discrimination was
      required at a cued location, by measuring electroencephalography following a
      central symbolic cue to deploy spatial attention. Electroencephalography activity
      in response to the cue revealed three cue-related activations: an early-onset
      positivity following the P1 at posterior scalp sites contralateral to the cued
      location, followed by cue-related frontal scalp activity and later-onset
      sustained activity at posterior scalp sites contralateral to the cued location.
      The early contralateral positivity may reflect rapid targeting of the cued
      location. Our results also extend the findings of cue-related frontal activity
      followed by posterior activity contralateral to the cued location, found with
      nonspatial feature discriminations, to a task requiring a spatial discrimination.

PMID- 17001276
TI  - Specificity of experience-dependent pitch representation in the brainstem.
AB  - Crosslanguage comparisons of brainstem-evoked potentials have revealed experience
      dependent plasticity in pitch representation for curvilinear f0 contours
      representative of Mandarin tones. To assess the tolerance limits of this
      experience-dependent selectivity, we evaluated cross-linguistically (Chinese,
      English) the pitch strength and tracking accuracy of linear rising and falling f0
      ramps representative of Mandarin tones 2 and 4. No crosslanguage differences in
      pitch strength or accuracy were observed for either tone, indicating that stimuli
      with linear rising/falling ramps elicit homogeneous pitch representations at the
      level of the brainstem regardless of language experience. We conclude that pitch
      extraction at the brainstem level is critically dependent on specific dimensions
      of pitch contours that native speakers have been exposed to in natural speech
      contexts.

PMID- 17001277
TI  - A role for the inferior colliculus in multisensory speech integration.
AB  - Multisensory integration can occur at relatively low levels within the central
      nervous system. Recent evidence suggests that multisensory audio-visual
      integration for speech may have a subcortical component, as acoustic processing
      in the human brainstem is influenced by lipreading during speech perception.
      Here, stimuli depicting the McGurk illusion (a demonstration of auditory-visual
      integration using speech stimuli) were presented to a 12-year-old child (FX) with
      a circumscribed unilateral lesion of the right inferior colliculus. When McGurk
      type stimuli were presented in the contralesional hemifield, illusory perception
      reflecting bimodal integration was significantly reduced compared with the
      ipsilesional hemifield and a group of age-matched controls. These data suggest a
      functional role for the inferior colliculus in the audio-visual integration of
      speech stimuli.

PMID- 17001278
TI  - A GABAergic component in the commissure of the inferior colliculus in rat.
AB  - The commissure of the inferior colliculus is significant as the final point of
      interconnection between homologous structures on the two sides of the auditory
      pathway at the subcortical level. The presence of excitatory fibres is well
      established in this tract, but the existence of an inhibitory component is
      controversial. Using rats, we injected biotinylated dextran amine into the
      inferior colliculus on one side to retrogradely label cells projecting through
      the commissure from the contralateral inferior colliculus. Immunocytochemistry
      for gamma-amino-n-butyric acid in neighbouring semithin sections revealed that
      20% of biotinylated dextran amine cell profiles were also labelled for gamma
      amino-n-butyric acid. We conclude that monosynaptic inhibitory connections
      contribute to the inhibition observed in the contralateral inferior colliculus in
      functional studies of the commissural projection.

PMID- 17001279
TI  - The role of spinal nuclear factor-kappa B in spinal hyperexcitability.
AB  - In behavioral experiments, inhibition of nuclear factor-kappaB activation by
      systemic administration of the IkappaB kinase inhibitor S1627 has been shown to
      attenuate inflammatory and neuropathic pain. Here, we specifically investigated
      with electrophysiological recordings in anesthetized rats whether spinal
      application of S1627 influences hyperexcitability of dorsal horn neurons during
      an acute knee joint inflammation. Spinal application of S1627 before and early
      during development of inflammation totally prevented spinal hyperexcitability
      suggesting an important role of spinal nuclear factor-kappaB in this process.
      During established inflammation, however, S1627 did not reduce the responses of
      neurons to mechanical stimulation of the inflamed knee within 2.5 h after spinal
      administration, thus suggesting that spinal hyperexcitability is not maintained
      by continuous nuclear factor-kappaB activation.

PMID- 17001280
TI  - Chronic activation of spinal adenosine A1 receptors results in hypersensitivity.
AB  - Spinally administered adenosine reduces hypersensitivity in animals and humans
      with nerve injury, but also causes transient pain in humans and reduces tonic
      inhibition in spinal neurons. Nerve injury results in increased tonic spinal cord
      adenosine A1 receptor activation, consistent with a role for adenosine to
      generate hypersensitivity. Here, we demonstrate that chronic intrathecal
      adenosine induces hypersensitivity in normal animals and that chronic blockade of
      spinal adenosine A1 receptors by the A1 antagonist 8-cyclopentyl-1,3
      dipropylxanthine partially prevents nerve injury-induced hypersensitivity. In
      contrast, chronic blockade of spinal adenosine A1 receptors failed to reduce
      increased tonic G-protein signaling in the spinal cord after nerve injury. These
      data support a role for chronic adenosine A1 receptor stimulation after nerve
      injury to result in hypersensitivity.

PMID- 17001281
TI  - Limbic neurogenesis/plasticity in the R6/2 mouse model of Huntington's disease.
AB  - Huntington's disease is an inherited neurodegenerative condition characterized by
      movement disorders, and mood and cognitive disturbance. Mammalian neurogenesis
      persists into adulthood in the subventricular zone and dentate gyrus of the
      hippocampus. Neurogenesis is abnormal in the dentate gyrus in the R6/2 transgenic
      mouse model of Huntington's disease. We have now found that the number of
      immature neurons (doublecortin-positive cells) is markedly reduced in the
      piriform and insular cortex but not in the temporal germinal layer or caudal
      subventricular zone of R6/2 mice. Furthermore, numbers of such cells were
      unaltered in response to seizures in both wild-type and R6/2 mice. These results
      support the possibility that impaired neurogenesis and/or plasticity could
      contribute to cognitive and psychiatric impairments in Huntington's disease.

PMID- 17001282
TI  - Cannabinoid self-administration increases dopamine release in the nucleus
      accumbens.
AB  - In the present study, dopamine release was monitored during cannabinoid self
      administration in rats to achieve a detailed understanding of the way in which
      dopamine mediates the reinforcing effects of cannabinoids. Extracellular dopamine
      levels were measured in the shell of the nucleus accumbens of either Lister
      Hooded or Long Evans rats trained to self-administer the cannabinoid CB1 receptor
      agonist WIN 55,212-2. A significant relationship between extracellular dopamine
      levels and bar-pressing rates was observed in both strains, as the dopamine
      content appreciably increased in respect to basal values during cannabinoid
      intake. Importantly, dopamine was not modified when trained rats were shifted to
      vehicle self-administration suggesting that an enhanced activity of the
      mesolimbic dopamine pathway underlies cannabinoid-taking behaviour.

PMID- 17001283
TI  - Dopamine-2 receptors in the arcuate nucleus modulate cocaine-seeking behavior.
AB  - Beta-endorphin is an endogenous opioid peptide, implicated in the behavioral
      effects of drugs of abuse. It is synthesized in the arcuate nucleus and secreted
      into the nucleus accumbens. In the present study, we examined the interaction
      between arcuate nucleus dopaminergic cells and accumbal beta-endorphin, during
      cocaine exposure. Using microdialysis, we found that blockade of arcuate dopamine
      2 receptors with a selective antagonist significantly attenuated cocaine-induced
      increases of beta-endorphin levels in the nucleus accumbens. Moreover, rats
      chronically exposed to cocaine using the self-administration paradigm displayed
      extinction-like behavior following blockade of dopamine-2 receptors. These
      findings indicate that dopaminergic neurons in the arcuate nucleus may induce the
      secretion of beta-endorphin in the nucleus accumbens, and that they are
      implicated in the cocaine reward pathway.

PMID- 17001284
TI  - The effect of the number of possible words on word completion: a
      magnetoencephalographic study.
AB  - We examined the effect of the number of possible words in a word completion task
      on left superior temporal activity using magnetoencephalography. If this area is
      involved in access to phonological word representations, as assumed in dual-route
      models of reading, its activation for word fragments having many possible words
      (Many condition) would be greater than for fragments with one possible word
      (Single condition). Left superior temporal activity did not differ in strength
      between the conditions, while behavioral data suggested multiple accesses in the
      Many condition. Activation was shorter in the Many than in the Single condition,
      probably owing to bigram frequency difference. These results are inconsistent
      with the view that the left superior temporal area is related to lexical-route
      processing.

PMID- 17001285
TI  - Brain dynamic mechanisms of scale effect in visual spatial attention.
AB  - The dynamic mechanisms of the early event-related potential scale effect of
      different attentive regions in the brain was studied. The paradigm of this
      experiment is the precue-target visual search paradigm by event-related potential
      technique. The results showed that the reaction time was shortened with the
      reduction of cue scale, a cue to how big the search area would be, and fixed
      target stimulus, while the amplitudes of P1 and N1 components of event-related
      potentials increased. These results not only provided the electrophysiological
      evidences that supported the zoom-lens theory, but also indicated that the zoom
      lens effect happened at the early selected attention period. The results also
      showed that there existed two kinds of separation in the P2 effect.

PMID- 17001286
TI  - Brain potentials associated with outcome expectation and outcome evaluation.
AB  - Feedback-related negativity is a negative deflection in brain potentials
      associated with feedback indicating monetary losses or response errors. Feedback
      related negativity is studied primarily in paradigms in which participants
      experience negative outcomes that appear to be contingent upon their previous
      choices. This study investigated whether feedback-related negativity can be
      elicited by a randomly assigned cue indicating potential monetary loss. The
      expected loss or win can be materialized or averted depending on participants'
      performance in a subsequent game. Compared with the win cue, the loss cue
      elicited a weak but significant feedback-related negativity-like effect. It is
      suggested that the anterior cingulate cortex, which generates feedback-related
      negativity, may function as a pre-warning system that alerts the brain to get
      ready for future events.

PMID- 17001287
TI  - Effect of cue-target interval on the N2pc.
AB  - The N2pc component of the event-related potential occurs when participants must
      select and process a lateralized visual target, often in the presence of one or
      more distractors. The goal of this research was to determine whether the N2pc
      reflects unique processing related to the treatment of the target or whether it
      reflects processing related to the presence of a distractor. The selection cue
      for the target was presented 100 ms earlier, at the same time as, or 100 ms later
      than the target itself. An earlier cue allowed earlier spatial selection, leading
      to less interference from the distractor. The results indicated that the offset
      of the N2pc was delayed when more interference from the distractor was expected.

PMID- 17001288
TI  - Pharmacogenetics of HIV therapy.
AB  - Drug treatment in HIV disease is characterized by variable responses, in terms of
      both efficacy and toxicity. Both genetic and environmental factors are important
      determinants of this variability, although the relative contributions are unclear
      and likely to vary with different drugs. Many of the antiretrovirals are
      metabolized by polymorphically expressed enzymes (cytochrome P450, CYP450;
      glucuronyl transferase, GT) and/or transported by drug transporters (ABC and SLC
      families). Initial studies of antiretroviral efficacy have therefore focused on
      these genes. For example, it has recently been shown that a CYP2B6 genetic
      variant predicts higher plasma efavirenz exposure and possibly increased central
      nervous system toxicity. A large number of studies on ABCB1 genetics with
      antiretrovirals have also been undertaken; however, as in other therapeutic
      areas, the data have been contradictory, and currently, no firm conclusions can
      be reached on the effect of ABCB1 variability as a determinant of efficacy.
      Indeed, this highlights the need for validation of initial association studies in
      pharmacogenetic research. By contrast, the clearest association between genetic
      variants and response relates to the hypersensitivity reaction that occurs with
      abacavir. The identification that the major histocompatibility complex haplotype
      57.1 acts as a strong genetic predisposing factor can be regarded as a prime
      example of how fundamental research can be translated into a pharmacogenetic
      test. Nevirapine hypersensitivity has also been related to an HLA gene (HLA
      DRB1*0101) but the predictive value does not appear to be sufficient to implement
      in clinical practice. Much more work needs to be done to define the genetic
      factors determining response to antiretroviral agents. These studies need to be
      sufficiently powered and utilize a modern genotyping strategy. Most importantly,
      the phenotype needs to be carefully characterized. We also need to disseminate
      this information: a pivotal resource for this can be found at www.HIV
      pharmacogenomics.org.

PMID- 17001289
TI  - An empirical evaluation of multifarious outcomes in pharmacogenetics: beta-2
      adrenoceptor gene polymorphisms in asthma treatment.
AB  - OBJECTIVE: Pharmacogenetics promises to individualize therapeutics. Concerns,
      however, exist about the lack of replication of discoveries. Selective use of
      different endpoints, times of assessment, types of interventions and genetic
      groups across studies may lead to spurious results. Here, we examined the
      variability of definitions of endpoints and analyses reported across studies
      addressing the association of the Arg16Gly and/or Gln27Glu polymorphisms of the
      beta2-adrenergic receptor gene with clinical response to beta2-agonist therapy in
      asthma. METHODS: We systematically calculated the number and type of endpoints
      and analyses reported across studies and recorded the appraisal of their
      statistical significance. RESULTS: Across 21 studies, the total number of probed
      and reported associations was 487 when the multiple endpoints and types of
      comparisons presented by multiple comparisons were considered (337 for Arg16Gly,
      98 for Gln27Glu and 52 for their haplotypes): 465 (95%) were probed only once;
      only six associations were probed twice and two associations were probed five
      times, for the same endpoint, time of assessment, type of interventions and
      genetic group. Most studies (17/21) claimed at least one significant association.
      Overall, however, 243/487 (49.9%) probed and reported associations were not
      statistically significant, 120 (24.6%) were of unspecified statistical
      significance, 86 (17.7%) were statistically significant only for specific
      selected genetic contrasts and only 38 (7.8%) were genuinely statistically
      significant for the comparison between all available genetic groups. CONCLUSIONS:
      The multifarious outcomes in this literature are inconsistent across studies and
      susceptible to selective reporting. The lack of standardization hinders the
      evaluation of replication validity for reported discoveries.

PMID- 17001290
TI  - Gene-gene interactions of IL13 and IL4RA variants in immediate allergic reactions
      to betalactam antibiotics.
AB  - OBJECTIVES: Immediate reactions - particularly anaphylactic ones - to betalactams
      are the most common adverse reactions to antibiotics mediated by a specific
      immunologic mechanism. The genetic risk factors influencing these mechanisms are
      poorly known. We aimed to evaluate the association between immediate allergic
      reactions to betalactams and the polymorphisms of IL13 (R130Q and -1055C>T
      variants) and IL4RA (I50V, S478P, and Q551R variants). METHODS: We determined
      these gene variants in 210 patients and 265 age-paired and gender-paired control
      subjects from Italy. RESULTS: The combination of the less frequent allele of the
      IL13 R130Q polymorphism with any of the predominant homozygous genotypes of the
      three polymorphisms of IL4RA was more significantly associated with the risk of
      betalactam allergy (P=0.0006, 0.0077, and 0.0041, respectively) than any
      polymorphism considered alone (P=0.1745, 0.0268, 0.1812, 0.0152, respectively).
      The same associations were observed with serum IgE levels (IL13/IL4RA variant
      combinations: P=0.0009, 0.0007, 0.0020, respectively and each variant: P=0.0201,
      0.0021, 0.0531, and 0.0417, respectively). The combination of IL4RA variants with
      -1055 C>T polymorphism produced similar associations. CONCLUSION: Our data
      suggest that these combinations of IL13 and IL4RA variants are predictors of
      immediate allergic reactions to betalactams through a mechanism related to IgE
      production.

PMID- 17001291
TI  - A common polymorphism in the SCN1A gene associates with phenytoin serum levels at
      maintenance dose.
AB  - OBJECTIVES: A broad range of phenytoin doses is used in clinical practice, with
      the final 'maintenance' dose normally determined by trial and error. A common
      functional polymorphism in the SCN1A gene (one of the genes encoding the drug
      target) has been previously associated with maximum dose of phenytoin used
      clinically, and also maximum dose of carbamazepine, another antiepileptic drug
      with the same drug target. METHODS: We have related variation at the SCN1A IVS5
      91 G>A polymorphism to maximum dose and to maintenance dose of phenytoin in 168
      patients with epilepsy treated with phenytoin. We also related genotype to
      phenytoin serum levels at maximum dose and at maintenance dose of phenytoin. We
      genotyped the polymorphism using an Applied Biosystems Taqman assay. RESULTS: The
      polymorphism is associated with phenytoin serum concentration at maintenance dose
      (P=0.03). In a reduced cohort of 71 patients receiving phenytoin monotherapy this
      association is also significant (P=0.03). Neither association remains significant
      after Bonferroni correction for multiple testing. CONCLUSIONS: These results are
      not a replication of the original study. They do, however, support the hypothesis
      that this polymorphism influences the clinical use of phenytoin. They also
      demonstrate the utility of using multiple phenotypes in pharmacogenetics studies,
      particularly when attempting to separate pharmacokinetic and pharmacodynamic
      effects. As the SCN1A polymorphism affects phenytoin pharmacodynamics, it is
      particularly useful to obtain data on serum levels in addition to dose because
      association of a pharmacodynamic variant may be stronger with serum levels than
      dose as the serum level may eliminate or reduce pharmacokinetic variability.

PMID- 17001292
TI  - The TNF/ADAM 17 system: implication of an ADAM 17 haplotype in the clinical
      response to infliximab in Crohn's disease.
AB  - Infliximab, a chimeric anti-tumour necrosis factor (TNF)-alpha antibody induces a
      clinical response in 70% of Crohn's disease patients and the response to
      infliximab therapy could be partially determined by genetic factors. The
      implication of both transmembrane and soluble forms of the TNF-alpha in the
      mechanism of action of infliximab has been demonstrated. The aim of our work was
      first to perform a complete study of TNF variants role in the response to
      infliximab in Crohn's disease. Secondly, considering the role of ADAM 17 in TNF
      alpha shedding, the ADAM 17 locus was also studied. The response to infliximab
      was evaluated in 222 Caucasian Crohn's disease patients with a luminal (n=160) or
      fistulizing (n=62) form of the disease. Clinical and biological response
      evaluation was based on the Crohn's Disease Activity Index score and C-reactive
      protein level evolutions, respectively. The entire TNF gene was sequenced on the
      complete cohort. Twelve single nucleotide polymorphisms spanning the ADAM 17
      locus were studied and haplotypes rebuilt. A clinical response was observed in
      64% of the patients and biological response in 77.1% of patients. No association
      was found between the TNF gene and the response to infliximab. One haplotype in
      the ADAM 17 region was associated with a clinical response to infliximab in CD
      patients (adjusted P=0.045). In conclusion, our results exclude, with a
      reasonable power, an implication of the TNF gene in the response to infliximab in
      Crohn's disease, but reveal a potential role of the ADAM 17 gene in this
      response.

PMID- 17001293
TI  - Highly variable mRNA expression and splicing of L-type voltage-dependent calcium
      channel alpha subunit 1C in human heart tissues.
AB  - OBJECTIVES: The voltage-dependent L-type calcium channel alpha-subunit 1c
      (Cav1.2, CACNA1C) undergoes extensive mRNA splicing, leading to numerous isoforms
      with different functions. L-type calcium channel blockers are used in the
      treatment of hypertension and arrhythmias, but response varies between
      individuals. We have studied the interindividual variability in mRNA expression
      and splicing of CACNA1C, in 65 heart tissue samples, taken from heart transplant
      recipients. METHODS: Splice variants were measured quantitatively by polymerase
      chain reaction in 12 splicing loci of CACNA1C mRNA. To search for functional cis
      acting polymorphisms, we determined allelic expression ratios for total CACNA1C
      mRNA and several splice variants using marker single nucleotide polymorphisms in
      exon 4 and exon 30. RESULTS: Total CACNA1C mRNA levels varied approximately 50
      fold. Substantial splicing occurred in six loci generating two or more splice
      variants, some with known functional differences. Splice patterns varied broadly
      between individuals. Two heart tissues expressed predominantly the
      dihydropyridine-sensitive smooth muscle isoform of CACNA1C (containing exon 8),
      rather than the cardiac isoform (containing exon 8a). Lack of significant allelic
      expression imbalance, observed with total mRNA and several splice variants,
      argued against CACNA1C polymorphisms as a cause of variability. Taken together,
      highly variable splicing can cause profound phenotypic variations of CACNA1C
      function, potentially associated with disease susceptibility and response to L
      type calcium channel blockers.

PMID- 17001294
TI  - Inflammation and apoptosis genes and the risk of restenosis after percutaneous
      coronary intervention.
AB  - OBJECTIVES: Genetic factors appear to be important in the development of
      restenosis after percutaneous coronary intervention, as well as in the process of
      inflammation, a pivotal factor in restenosis. Caspase-1, interleukin-1-receptor
      and protein tyrosine phosphatase nonreceptor type 22 are important mediators in
      the inflammatory response and caspase-1 also in apoptosis. Therefore, we examined
      whether polymorphisms in these candidate genes are related to the risk of
      developing restenosis after percutaneous coronary intervention. METHODS: The
      GENetic DEterminants of Restenosis-project is a multicenter prospective follow-up
      study. The 5352G/A (L235L) caspase-1-polymorphism, the 7464C/G (A124G)
      interleukin-1r-polymorphism and the 1858C/T (R620W) protein tyrosine phosphatase
      nonreceptor type 22-polymorphism were genotyped. To examine the functional effect
      of the caspase-1 polymorphism, mature plasma interleukin-1beta levels were
      measured by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated
      whole blood from a subpopulation of patients. RESULTS: A total of 3104 patients,
      age 62.1+/-10.7 years, were included after successful percutaneous coronary
      intervention. A significant association between the 5352AA genotype of the
      caspase-1 gene and target vessel revascularization (relative risk 2.2, 95%
      confidence interval 1.32-3.76) was observed after correcting for clinical
      variables. Angiographic analysis of a subgroup of patients (N=478) also showed an
      increased risk for developing restenosis for patients having the 5352GA/AA
      genotype (P=0.001). The results were corroborated, although they were not
      statistically significant, by somewhat higher mature interleukin-1beta levels in
      patients with the 5352AA genotype. CONCLUSIONS: The present study shows that
      patients with the 5352AA genotype in the caspase-1 gene are at increased risk of
      developing restenosis. If confirmed by other studies, screening patients for this
      genotype can lead to better risk stratification and provide indications for
      improving individual treatment; for instance, by providing a new target for drug
      eluting stents.

PMID- 17001295
TI  - Impaired expression of CYP2D6 in intermediate metabolizers carrying the *41
      allele caused by the intronic SNP 2988G>A: evidence for modulation of splicing
      events.
AB  - We investigated the molecular basis for low expression and activity of CYP2D6
      associated with the CYP2D6*41 allele in about 10-15% of Caucasians with
      intermediate metabolizer phenotype. With respect to two previously described
      polymorphisms in the promoter (-1584C>G) and in intron 6 (2988G>A; c.985+39G>A),
      the three most frequent functional alleles have the distinct haplotypes
      2D6*1[CG], 2D6*2[GG] and 2D6*41[CA], respectively. Reporter gene analyses in
      transiently transfected HepG2 and Huh7 hepatoma cells did not indicate changes in
      transcription rate by these polymorphisms. By reverse-transcription polymerase
      chain reaction analysis of liver RNA of genotyped patients, however, we
      discovered that the 2988G>A change was associated with increased levels of a
      nonfunctional splice variant lacking exon 6. Quantification by denaturing high
      performance liquid chromatography revealed up to 7.3-fold increased levels of the
      splice variant and up to 2.9-fold less functional transcript in carriers of
      2D6*41, in good concordance with concomitant changes in immunoquantified CYP2D6
      protein. Recombinant expression of the entire genomic sequence coding for 2D6*41,
      2D6*2 and 2D6*1 alleles but lacking the upstream region in COS-1 and Huh7 cell
      lines resulted in two-fold to five-fold reduced levels of CYP2D6 mRNA containing
      exon 6, apoprotein and enzyme activity of 2D6*41. These experiments establish the
      causal relationship between the intron 6 single-nucleotide polymorphism 2988G>A
      and the low expression phenotype associated with allele 2D6*41. These data
      improve the CYP2D6 genotype-phenotype relationship and they demonstrate that
      major phenotype changes occurring in large population subgroups can be caused by
      intronic polymorphisms outside of splice site consensus sequences.

PMID- 17001296
TI  - A silent mutation (2939G>A, exon 6; CYP2D6*59) leading to impaired expression and
      function of CYP2D6.
AB  - We analyzed CYP2D6 in two individuals characterized by impaired sparteine
      oxidation (intermediate metabolizer phenotype) and genotype 2D62/4 (1661G>C;
      2850C>T; 4180G>C) usually associated with normal function. Full genomic
      sequencing and haplotype analysis confirmed the previously identified silent
      mutation 2939G>A in exon 6 (former allele variant 2D62J, now termed 2D659), as
      well as an additional novel 2291G>A change in intron 4. Transient expression in
      Huh7 hepatoma cells of the entire CYP2D6 gene of constructs carrying either both
      or only the 2939G>A change resulted in about three-fold reduced levels of mRNA,
      immunoreactive 2D6 protein and propafenone hydroxylase activity. These data
      demonstrate profound effects of a silent mutation on expression and function of
      CYP2D6, resulting in impaired drug oxidation phenotype. The 2939G>A single
      nucleotide polymorphism in exon 6 was present heterozygously in two individuals
      out of 308 (0.65%), corresponding to an allele frequency of 0.3%. Genotyping for
      this mutation thus improves phenotype-genotype correlation for CYP2D6 and may
      help to predict adverse drug treatment events.

PMID- 17001297
TI  - Three new combination oral contraceptives: Seasonique, Loestrin 24 Fe, and Yaz.

PMID- 17001298
TI  - A once-daily combination tablet (Atripla) for HIV.

PMID- 17001299
TI  - A second dose of varicella vaccine.

PMID- 17001300
TI  - Na+-K+-ATPase is involved in the sustained ACh-induced hyperpolarization of
      endothelial cells from rat aorta.
AB  - BACKGROUND AND PURPOSE: Inhibition of Na(+)-K(+)-ATPase is known to attenuate
      endothelium-dependent relaxation in many arteries. The purpose of this study was
      to evaluate the role of Na(+)-K(+)-ATPase in the regulation of endothelial
      membrane potential at rest and during stimulation by ACh. EXPERIMENTAL APPROACH:
      Membrane potential was recorded from the endothelium of rat aorta using the
      perforated patch-clamp technique. KEY RESULTS: Superfusion with K(+)-free
      solution produced a depolarization of about 11 mV from the resting value of 
      42.9+/-0.9 mV. Reintroduction of 4.7 mM K(+) transiently hyperpolarized
      endothelial cells to -52.4+/-1.8 mV and the membrane potential recovered within
      10 min. Ouabain 500 microM depolarized endothelium by about 11 mV and inhibited
      the hyperpolarization induced by K(+) reintroduction into the K(+)-free solution.
      However, 500 nM ouabain did not affect the resting membrane potential or the
      hyperpolarization induced by K(+) reintroduction. Pre-exposure to ouabain 500
      microM, but not 500 nM, attenuated the sustained component of hyperpolarization
      to ACh without affecting the amplitude of the transient peak hyperpolarization.
      In K(+)-free solution, the amplitude of peak hyperpolarization to ACh was
      increased, while the sustained component of hyperpolarization was attenuated.
      CONCLUSIONS AND IMPLICATIONS: These results indicate that electrogenic Na(+)-K(+)
      ATPase partially contributes to the sustained hyperpolarization of endothelial
      cells from rat aorta in response to ACh. They also suggest that the alpha1, but
      not alpha2 or alpha3 isoforms, is involved in ACh-mediated hyperpolarization.

PMID- 17001301
TI  - Inhibition by alpha-tetrahydrodeoxycorticosterone (THDOC) of pre-sympathetic
      parvocellular neurones in the paraventricular nucleus of rat hypothalamus.
AB  - BACKGROUND AND PURPOSE: alpha-tetrahydrodeoxycorticosterone (THDOC) is an
      endogenous neuroactive steroid which increases in plasma and brain concentration
      during stress. It has both positive and negative modulatory effects on GABA
      activated GABAA currents, dependent upon the dose. We investigated the effects of
      THDOC on spinally-projecting "pre-sympathetic" neurones in the parvocellular
      subnucleus of the hypothalamic paraventricular nucleus (PVN), to determine
      whether it activates or inhibits these neurones, and by what mechanism.
      EXPERIMENTAL APPROACH: Rat spinally-projecting (parvocellular) PVN neurones were
      identified by retrograde labelling and the action of THDOC investigated with
      three modes of patch-clamp: cell-attached action current, whole-cell voltage
      clamp and cell-attached single-channel recording. KEY RESULTS: In cell-attached
      patch mode, parvocellular neurones fired action potentials spontaneously with an
      average frequency of 3.6 +/- 1.1 Hz. Bath application of THDOC reduced this with
      an EC50 of 67 nM (95% confidence limits: 54 to 84 nM), Hill coefficient 0.8 +/-
      0.04, n = 5. In whole-cell patch-clamp mode, pressure ejection of GABA evoked
      inward currents. These were clearly GABAA currents, since they were inhibited by
      the GABAA receptor antagonist bicuculline, and reversed near the chloride
      equilibrium potential. THDOC significantly potentiated GABAA currents (1 microM
      THDOC: 148 +/- 15% of control, n = 5, p < or = 0.05, ANOVA). Single-channel
      analysis showed no differences in conductance or corrected mean open times in the
      presence of 1 microM THDOC. CONCLUSIONS AND IMPLICATIONS: THDOC inhibited
      parvocellular neuronal activity without showing any evidence of the bidirectional
      activity demonstrated previously with cultured hypothalamic neurones. Our data
      are consistent with the hypothesis that THDOC acts by potentiating the post
      synaptic activity of endogenously released GABA.

PMID- 17001302
TI  - Tails of the unexpected - an atypical receptor for the chemokine RANTES/CCL5
      expressed in brain.
AB  - Chemokines and their receptors play a central role in the trafficking of
      leukocytes within the body, a process which is amenable to antagonism by small
      molecules and which holds promise as a treatment for clinically important
      diseases. In the issue of the British Journal of Pharmacology accompanying this
      commentary, Ignatov and colleagues describe an unexpected role for the chemokine
      RANTES/CCL5, namely an ability to signal via the orphan G protein-coupled
      receptor named GPR75. This receptor bears little homology to other chemokine
      receptors, most strikingly within the putative intracellular domains, with the
      third loop and C-terminal tail dwarfing those of other known chemokine receptors.
      This most likely accounts for the atypical pertussis toxin-insensitive signalling
      induced by RANTES. Intriguingly, this signalling is neuro-protective, inducing
      the survival of a hippocampal cell line following insult with the neurotoxic
      amyloid-beta peptide. Since this peptide is implicated in the pathogenesis of
      Alzheimer's disease, it may be that exploitation of this signalling pathway
      presents itself as a future therapeutic treatment.

PMID- 17001303
TI  - RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in
      cells transfected with G protein-coupled receptor 75.
AB  - BACKGROUND AND PURPOSE: RANTES is an inflammatory chemokine with a critical role
      in T-lymphocyte activation and proliferation. Its effects are mediated through G
      protein-coupled heptahelical receptors (GPCRs). We show for the first time that
      RANTES activates the orphan G protein-coupled receptor 75 (GPR75). EXPERIMENTAL
      APPROACH: To identify a ligand for GPR75 we have used three different and
      independent methods, namely luciferase assay, bioluminescence assay and IP3
      accumulation assay. KEY RESULTS: Treatment of cells expressing GPR75 with
      subnanomolar concentrations of RANTES led to stimulation of the luciferase
      activity in a reporter-gene assay, an increase in inositol trisphosphate, and
      intracellular Ca2+. The latter effect was blocked by the phospholipase-C
      inhibitor (PLC) U73122 indicating that Gq proteins mediate GPR75 signaling.
      RANTES enhanced the phosphorylation of AKT and mitogen-activated protein kinase
      (MAPK) in GPR75-transfected cells and this effect was blocked by the PLC
      inhibitor U73122 and the phosphatidylinositol 3-kinase (PI3K) inhibitor,
      wortmannin. The hippocampal cell line HT22, which expresses GPR75 endogenously,
      but not the other known RANTES receptors, was used to study the effects of RANTES
      and GPR75 on neuronal survival. Treatment of HT22 cells with RANTES significantly
      reduced the neurotoxicity of amyloid-beta peptides, by activating PLC and PI3K.
      CONCLUSIONS AND IMPLICATIONS: This demonstrate clearly and undoubtedly the
      ability of RANTES to act on GPR75. Defects in the RANTES/GPR75-signaling pathway
      may contribute to neuroinflammatory and neurodegenerative processes as observed
      in Alzheimer's disease.

PMID- 17001304
TI  - A key role for the subunit SUR2B in the preferential activation of vascular KATP
      channels by isoflurane.
AB  - BACKGROUND AND PURPOSE: It has been postulated that isoflurane, a volatile
      anaesthetic, produces vasodilatation through activation of ATP-sensitive K+
      (KATP) channels. However, there is no direct evidence for the activation of
      vascular KATP channels by isoflurane. This study was conducted to examine the
      effect of isoflurane on vascular KATP channels and compare it with that on
      cardiac KATP channels. EXPERIMENTAL APPROACH: Effects of isoflurane on KATP
      channels were examined in aortic smooth muscle cells and cardiomyocytes of the
      mouse using patch clamp techniques. Effects of the anaesthetic on the KATP
      channels with different combinations of the inward rectifier pore subunits
      (Kir6.1 and Kir6.2) and sulphonylurea receptor subunits (SUR2A and SUR2B)
      reconstituted in a heterologous expression system were also examined. KEY
      RESULTS: Isoflurane increased the coronary flow in Langendorff-perfused mouse
      hearts in a concentration-dependent manner, which was abolished by 10 microM
      glibenclamide. In enzymically-dissociated aortic smooth muscle cells, isoflurane
      evoked a glibenclamide-sensitive current (i.e. KATP current). In isolated mouse
      ventricular cells, however, isoflurane failed to evoke the KATP current unless
      the KATP current was preactivated by the K+ channel opener pinacidil. Although
      isoflurane readily activated the Kir6.1/SUR2B channels (vascular type), the
      volatile anesthetic could not activate the Kir6.2/SUR2A channels (cardiac type)
      expressed in HEK293 cells. Isoflurane activated a glibenclamide-sensitive current
      in HEK293 cells expressing Kir6.2/SUR2B channels. CONCLUSION AND IMPLICATIONS:
      Isoflurane activates KATP channels in vascular smooth muscle cells and produces
      coronary vasodilation in mouse hearts. SUR2B may be important for the activation
      of vascular-type KATP channels by isoflurane.

PMID- 17001305
TI  - The insulin receptor is essential for virus-induced tumorigenesis of Kaposi's
      sarcoma.
AB  - Kaposi sarcoma (KS), a multifocal neoplasm of the skin that can spread to
      visceral organs, is the most prevalent malignant tumor in acquired immuno
      deficiency syndrome (AIDS) patients. KS-associated herpesvirus (KSHV or HHV8) is
      considered the primary etiological factor of this malignancy, as well as of
      primary effusion lymphoma and multicentric Castleman's disease. KS lesions are
      characterized by proliferating spindle cells of endothelial cell (EC) origin. The
      action of the insulin-like growth factor (IGF) system has been implicated in many
      malignancies, and recent data have demonstrated that the IGF-I receptor (IGF-IR)
      is required for in vitro growth of the KS-derived KSIMM cell line. To examine
      whether the IGF pathway is also involved in KSHV-mediated transformation of ECs,
      we examined the expression and function of the IGF system in KSHV-infected,
      immortalized dermal microvascular EC (E-DMVEC). The expression of the insulin
      receptor (IR) was strongly induced in latently infected E-DMVEC, whereas the
      expression levels of the IGF-IR remained unchanged. Gene knockdown of IR, but not
      IGF-IR, prevented the characteristic focus formation seen in KSHV-infected E
      DMVEC. Similarly, treatment with the IR-specific small-molecule inhibitor HNMPA
      (AM(3)) inhibited postconfluent growth. These data suggest a role for the IR, but
      not the IGF-IR, in KSHV-induced transformation of vascular ECs.

PMID- 17001306
TI  - Novel role of WD40 and SOCS box protein-2 in steady-state distribution of
      granulocyte colony-stimulating factor receptor and G-CSF-controlled proliferation
      and differentiation signaling.
AB  - Signals induced by granulocyte colony-stimulating factor (G-CSF), the major
      cytokine involved in neutrophil development, are tightly controlled by ligand
      induced receptor internalization. Truncated G-CSF receptors (G-CSF-Rs) that fail
      to internalize show sustained proliferation and defective differentiation
      signaling. Steady-state forward routing also determines cell surface levels of
      cytokine receptors, but mechanisms controlling this are poorly understood. Here,
      we show that WD40 and suppressor of cytokine signaling (SOCS) box protein-2 (Wsb
      2), an SOCS box-containing WD40 protein with currently unknown function, binds to
      the COOH-terminal region of G-CSF-R. Removal of this region did not affect
      internalization, yet resulted in increased membrane expression of G-CSF-R and
      enhanced proliferation signaling at the expense of differentiation induction.
      Conversely, Wsb-2 binding to the G-CSF-R reduced its cell surface expression and
      inhibited proliferation signaling. These effects depended on the SOCS box
      involved in ubiquitylation and on cytosolic lysines of G-CSF-R and imply a major
      role for ubiquitylation through the G-CSF-R C-terminus in forward routing of the
      receptor. Importantly, the Wsb-2 gene is commonly disrupted by virus integrations
      in mouse leukemia. We conclude that control of forward routing of G-CSF-R is
      essential for a balanced response of myeloid progenitors to G-CSF and suggest
      that disturbance of this balance may contribute to myeloid leukemia.

PMID- 17001307
TI  - Identification of an histone H3 acetylated/K4-methylated-bound intragenic
      enhancer regulatory for urokinase receptor expression.
AB  - The transcriptionally regulated urokinase-type plasminogen activator receptor (u
      PAR) contributes to cancer progression. Although previous studies have identified
      multiple 5' regulatory elements, these cis motifs cannot fully account for u-PAR
      expression prompting a search for hitherto uncharacterized regulatory elements.
      DNase I hypersensitivity and chromatin immunoprecipitation assays using u-PAR
      expressing colon cancer cells indicated a hypersensitive region (+665/+2068) in
      intron 1 enriched with acetylated histone 3 (H3) and H3 methylated at lysine 4,
      markers of regulatory regions. The +665/+2068 region increased transcription from
      a u-PAR-promoter in an orientation- and distance-independent manner fulfilling
      the criteria of an enhancer. Optimal stimulation of the u-PAR promoter by phorbol
      ester required this enhancer. Systematic truncations combined with DNase I
      footprinting revealed two protected regions (+1060/+1099 and +1123/+1134) with
      deletion of the latter practically abolishing enhancer activity. The +1123/+1134
      region harbored non-consensus activator protein-1 and Ets1 binding sites bound
      with c-Jun (and/or the related JunD/JunB) and c-Fos (and/or the related FosB/Fra
      1/Fra-2) as revealed with chromatin immunoprecipitation. Further, nuclear extract
      from resected colon cancers showed elevated protein binding to a +1123/+1134
      spanning probe coordinate with elevated u-PAR protein. Thus, we have defined a
      novel intragenic enhancer in the u-PAR gene required for constitutive and
      inducible expression.

PMID- 17001308
TI  - Transforming function of the LSM1 oncogene in human breast cancers with the 8p11
      12 amplicon.
AB  - Amplification of the 8p11-12 region occurs in 15-20% of breast cancers, but the
      driving oncogene at this locus has yet to be definitively identified. We mapped
      the 8p11-12 amplicon in breast cancer cell lines and primary human breast cancers
      and identified the candidate oncogene human Sm-like protein (hLsm1, LSM1) based
      on increases in copy number and expression level relative to human mammary
      epithelial cells. To examine the oncogenic role of LSM1, we overexpressed this
      gene in MCF10A mammary epithelial cells and inhibited its production in the SUM44
      breast cancer cell line, which has a natural amplification and overexpression of
      LSM1. Our data confirmed that LSM1 is an oncogene from the 8p11-12 amplicon by
      showing that hLsm1 overexpression induced growth factor-independent proliferation
      and soft agar colony formation in MCF10A cells, and hLsm1 inhibition in SUM44
      cells dramatically reduced soft agar growth. Little is known about hLsm1 function
      other than its involvement in mRNA degradation; therefore, we used expression
      microarray analysis to investigate how hLsm1 affects cell transformation in
      MCF10A and SUM44 cells. We identified numerous genes altered following hLsm1
      overexpression common to SUM44 breast cancer cells that play important roles in
      cell cycle regulation, cell proliferation and other cancer-promoting processes.
      Future work will continue to characterize these important changes to achieve a
      more complete understanding of the mechanism of hLsm1's effect on cancer
      progression.

PMID- 17001309
TI  - Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia.
AB  - We and others have shown that the dysregulation of DNA repair pathways can
      contribute to the phenomenon of hypoxia-induced genetic instability within the
      tumor microenvironment. Several studies have revealed that the recombinational
      repair genes, RAD51 and BRCA1, and the DNA mismatch repair genes, MLH1 and MSH2,
      are decreased in expression in response to hypoxic stress, prompting interest in
      elucidating the mechanistic basis for these responses. Here we report that the
      downregulation of RAD51 by hypoxia is specifically mediated by repressive
      E2F4/p130 complexes that bind to a single E2F site in the proximal promoter of
      the gene. Intriguingly, this E2F site is conserved in the promoter of the BRCA1
      gene, which is also regulated by a similar mechanism in hypoxia. Mechanistically,
      we have found that hypoxia induces substantial p130 dephosphorylation and nuclear
      accumulation, leading to the formation of E2F4/p130 complexes and increased
      occupancy of E2F4 and p130 at the RAD51 and BRCA1 promoters. These findings
      reveal a coordinated transcriptional program mediated by the formation of
      repressive E2F4/p130 complexes that represents an integral response to hypoxic
      stress. In addition, this co-regulation of key factors within the homology
      dependent DNA repair pathway provides a further basis for understanding genetic
      instability in tumors and may guide the design of new therapeutic strategies for
      cancer.

PMID- 17001310
TI  - Heparin-binding EGF-like growth factor is an early response gene to chemotherapy
      and contributes to chemotherapy resistance.
AB  - We have shown that one of the principle mechanisms of chemotherapy resistance
      involves the activation of nuclear factor kappa-B (NF-kappaB). In an effort to
      identify NF-kappaB-regulated chemotherapy response genes, we performed a
      microarray assay and observed that heparin-binding EGF-like growth factor (HB
      EGF) was significantly upregulated by SN38 (a strong inducer of NF-kappaB
      activity) in colon cancer cells. Further studies revealed that HB-EGF was rapidly
      induced following a variety of chemotherapy treatments. Using RNA interference,
      we demonstrated that the chemotherapy-induced HB-EGF was largely dependent on
      activator protein-1 (AP-1) and NF-kappaB activation. Constitutive HB-EGF
      expression rescued AP-1/NF-kappaB small interfering RNA (siRNA) cells from
      chemotherapy-induced apoptosis. Meanwhile, we found that the enzymatic shedding
      of HB-EGF was also regulated by chemotherapy treatment, resulting in the elevated
      release of soluble HB-EGF from the cellular membrane. Induction of HB-EGF
      expression and ectodomain shedding synergistically led to robust epidermal growth
      factor receptor (EGFR) phosphorylation, whereas inhibition of HB-EGF expression
      by use of the HB-EGF inhibitor (CRM197) or siRNA resulted in the suppression of
      chemotherapy-induced EGFR phosphorylation. These results suggest that the
      chemotherapy-induced EGFR activation is regulated by HB-EGF. Finally, we
      demonstrated that overexpression of HB-EGF led to apoptotic resistance to
      chemotherapy, whereas suppression of HB-EGF expression by siRNA resulted in a
      dramatic increase in cell death. In summary, our study suggests that chemotherapy
      induced HB-EGF activation represents a critical mechanism of inducible
      chemotherapy resistance. Therefore, therapeutic intervention aimed at inhibiting
      HB-EGF activity may be useful in cancer prevention and treatments.

PMID- 17001311
TI  - Chromosomes with delayed replication timing lead to checkpoint activation,
      delayed recruitment of Aurora B and chromosome instability.
AB  - Certain chromosome rearrangements display a significant delay in chromosome
      replication timing (DRT) that is associated with a subsequent delay in mitotic
      chromosome condensation (DMC). DRT/DMC chromosomes are common in tumor cells in
      vitro and in vivo and occur frequently in cells exposed to ionizing radiation. A
      hallmark for these chromosomes is the delayed phosphorylation of serine 10 of
      histone H3 during mitosis. The chromosome passenger complex, consisting of
      multiple proteins including Aurora B kinase and INCENP is thought to be
      responsible for H3 phosphorylation, chromosome condensation and the subsequent
      segregation of chromosomes. In this report, we show that chromosomes with DRT/DMC
      contain phosphorylated Chk1, consistent with activation of the S-M phase
      checkpoint. Furthermore, we show that INCENP is recruited to the DRT/DMC
      chromosomes during all phases of mitosis. In contrast, Aurora B kinase is absent
      on DRT/DMC chromosomes when these chromosomes lack serine 10 phosphorylation of
      H3. We also show that mitotic arrest deficient 2 (Mad2), a member of the spindle
      assembly checkpoint, is present on DRT/DMC chromosomes at a time when the
      normally condensed chromosomes show no Mad2 staining, indicating that DRT/DMC
      activates the spindle assembly checkpoint. Finally, cells with DRT/DMC
      chromosomes have centrosome amplification, abnormal spindle assembly,
      endoreduplication and significant chromosome instability.

PMID- 17001312
TI  - Expression of SOCS1 and SOCS3 genes is differentially regulated in breast cancer
      cells in response to proinflammatory cytokine and growth factor signals.
AB  - DNA-hypermethylation of SOCS genes in breast, ovarian, squamous cell and
      hepatocellular carcinoma has led to speculation that silencing of SOCS1 and SOCS3
      genes might promote oncogenic transformation of epithelial tissues. To examine
      whether transcriptional silencing of SOCS genes is a common feature of human
      carcinoma, we have investigated regulation of SOCS genes expression by IFNgamma,
      IGF-1 and ionizing radiation, in a normal human mammary epithelial cell line
      (AG11134), two breast-cancer cell lines (MCF-7, HCC1937) and three prostate
      cancer cell lines. Compared to normal breast cells, we observe a high level
      constitutive expression of SOCS2, SOCS3, SOCS5, SOCS6, SOCS7, CIS and/or SOCS1
      genes in the human cancer cells. In MCF-7 and HCC1937 breast-cancer cells,
      transcription of SOCS1 is dramatically up-regulated by IFNgamma and/or ionizing
      radiation while SOCS3 is transiently down-regulated by IFNgamma and IGF-1,
      suggesting that SOCS genes are not silenced in these cells by the epigenetic
      mechanism of DNA-hypermethylation. We further show that the kinetics of SOCS1
      mediated feedback inhibition of IFNgamma signaling is comparable to normal breast
      cells, indicating that the SOCS1 protein in breast-cancer cells is functional. We
      provide direct evidence that STAT3 pathways are constitutively activated in MCF-7
      and HCC1937 cells and may drive the aberrant persistent activation of SOCS genes
      in breast-cancer cells. Our data therefore suggest that elevated expression of
      SOCS genes is a specific lesion of breast-cancer cells that may confer resistance
      to proinflammatory cytokines and trophic factors, by shutting down STAT1/STAT5
      signaling that mediate essential functions in the mammary gland.

PMID- 17001313
TI  - Silencing mammalian target of rapamycin signaling by small interfering RNA
      enhances rapamycin-induced autophagy in malignant glioma cells.
AB  - The mammalian target of rapamycin (mTOR) plays a central role in regulating the
      proliferation of malignant glioma cells, and mTOR-specific inhibitors such as
      rapamycin analogs are considered as promising therapy for malignant gliomas.
      However, the efficacy of mTOR inhibitors alone in the treatment of patients with
      malignant gliomas is only modest, potentially because these agents rather than
      acting as mTOR kinase inhibitors instead interfere with the function of only
      mTOR/raptor (regulatory-associated protein of mTOR) complex and thus do not
      perturb all mTOR functions. The purpose of this study was to determine whether
      global inhibition of the mTOR molecule enhances the antitumor effect of rapamycin
      on malignant glioma cells. We showed that rapamycin induced autophagy and that
      inhibition of autophagy by small interfering RNA (siRNA) directed against
      autophagy-related gene Beclin 1 attenuated the cytotoxicity of rapamycin in
      rapamycin-sensitive tumor cells, indicating that the autophagy was a primary
      mediator of rapamycin's antitumor effect rather than a protective response.
      Exogenous expression of an mTOR mutant interfering with its kinase activity
      markedly enhanced the incidence of rapamycin-induced autophagy. Moreover,
      silencing of mTOR with siRNA augmented the inhibitory effect of rapamycin on
      tumor cell viability by stimulating autophagy. Importantly, not only rapamycin
      sensitive malignant glioma cells with PTEN mutations but also rapamycin-resistant
      malignant glioma cells with wild-type PTEN were sensitized to rapamycin by mTOR
      siRNA. These results indicate that rapamycin-induced autophagy is one of the
      agent's antitumor effects and that silencing or inhibiting mTOR kinase activity
      could enhance the effectiveness of rapamycin.

PMID- 17001314
TI  - Rapamycin induces feedback activation of Akt signaling through an IGF-1R
      dependent mechanism.
AB  - Rapamycin and several analogs, such as CCI-779 and RAD001, are currently
      undergoing clinical evaluation as anticancer agents. In this study, we show that
      inhibition of mammalian target of rapamycin (mTOR) signaling by rapamycin leads
      to an increase of Akt phosphorylation in Rh30 and RD human rhabdomyosarcoma cell
      lines and xenografts, and insulin-like growth factor (IGF)-II-treated C2C12 mouse
      myoblasts and IGF-II-overexpressing Chinese hamster ovary cells. RNA interference
      mediated knockdown of S6K1 also results in an increase of Akt phosphorylation.
      These data suggest that mTOR/S6K1 inhibition either by rapamycin or small
      interfering RNA (siRNA) triggers a negative feedback loop, resulting in the
      activation of Akt signaling. We next sought to investigate the mechanism of this
      negative feedback regulation from mTOR to Akt. Suppression of insulin receptor
      substrate (IRS)-1 and tuberous sclerosis complex-1 by siRNAs failed to abrogate
      rapamycin-induced upregulation of Akt phosphorylation in both Rh30 and RD cells.
      However, pretreatment with h7C10 antibody directed against insulin-like growth
      factor-1 receptor (IGF-1R) led to a blockade of rapamycin-induced Akt activation.
      Combined mTOR and IGF-1R inhibition with rapamycin and h7C10 antibody,
      respectively, resulted in additive inhibition of cell growth and survival. These
      data suggest that rapamycin mediates Akt activation through an IGF-1R-dependent
      mechanism. Thus, combining an mTOR inhibitor and an IGF-1R antibody/inhibitor may
      be an appropriate strategy to enhance mTOR-targeted anticancer therapy.

PMID- 17001315
TI  - p53 downregulates expression of the G1/S cell cycle phosphatase Cdc25A.
AB  - Overexpression of Cdc25A phosphatase is often observed in cancer and results in
      poor prognosis. Cdc25A mainly dephosphorylates and thereby activates Cyclin
      dependent kinase 2 and thus induces progression in the cell cycle from G(1) to S
      phase. Here, we demonstrate that the tumor suppressor p53 downregulates
      expression from the Cdc25A gene. In a p53-inducible cell system, Cdc25A
      expression on the mRNA and protein level is downregulated upon p53 expression.
      Promoter-reporter assays show that this regulation is dependent on the Cdc25A
      promoter. Mutant p53 fails to reduce Cdc25A transcription. In contrast to p53,
      neither p63 nor p73 can repress Cdc25A transcription. The Cdc25A promoter
      displays no p53 binding site, and p53 does not bind directly to the promoter DNA
      as shown by chromatin immunoprecipitation assays. Previously, the contribution of
      p53 to G(1)/S arrest has been mostly linked to activating the expression of the
      Cdk inhibitor p21(WAF1/CIP1). By downregulating Cdc25A expression, p53 may impair
      transition from G(1) to S phase independently of p21(WAF1/CIP1). Therefore, the
      data suggest that, as long as p53 is intact, Cdc25A transcriptional
      downregulation might play a role in cancer prevention.

PMID- 17001316
TI  - PHC3, a component of the hPRC-H complex, associates with E2F6 during G0 and is
      lost in osteosarcoma tumors.
AB  - Polyhomeotic-like 3 (PHC3) is a ubiquitously expressed member of the polycomb
      gene family and part of the human polycomb complex hPRC-H. We found that in
      normal cells PHC3 associated with both hPRC-H complex components and with the
      transcription factor E2F6. In differentiating and confluent cells, PHC3 and E2F6
      showed nuclear colocalization in a punctate pattern that resembled the binding of
      polycomb bodies to heterochromatin. This punctate pattern was not seen in
      proliferating cells suggesting that PHC3 may be part of an E2F6-polycomb complex
      that has been shown to occupy and silence target promoters in G(0). Previous loss
      of heterozygosity (LoH) analyses had shown that the region containing PHC3
      underwent frequent LoH in primary human osteosarcoma tumors. When we examined
      normal bone and human osteosarcoma tumors, we found loss of PHC3 expression in 36
      of 56 osteosarcoma tumors. Sequence analysis revealed that PHC3 was mutated in
      nine of 15 primary osteosarcoma tumors. These findings suggest that loss of PHC3
      may favor tumorigenesis by potentially disrupting the ability of cells to remain
      in G(0).

PMID- 17001317
TI  - Using array-comparative genomic hybridization to define molecular portraits of
      primary breast cancers.
AB  - We analysed 148 primary breast cancers using BAC-arrays containing 287 clones
      representing cancer-related gene/loci to obtain genomic molecular portraits.
      Gains were detected in 136 tumors (91.9%) and losses in 123 tumors (83.1%). Eight
      tumors (5.4%) did not have any genomic aberrations in the 281 clones analysed.
      Common (more than 15% of the samples) gains were observed at 8q11-qtel, 1q21
      qtel, 17q11-q12 and 11q13, whereas common losses were observed at 16q12-qtel,
      11ptel-p15.5, 1p36-ptel, 17p11.2-p12 and 8ptel-p22. Patients with tumors
      registering either less than 5% (median value) or less than 11% (third quartile)
      total copy number changes had a better overall survival (log-rank test: P=0.0417
      and P=0.0375, respectively). Unsupervised hierarchical clustering based on copy
      number changes identified four clusters. Women with tumors from the cluster with
      amplification of three regions containing known breast oncogenes (11q13, 17q12
      and 20q13) had a worse prognosis. The good prognosis group (Nottingham Prognostic
      Index (NPI) <or=3.4) tumors had frequent loss of 16q24-qtel. Genes significantly
      associated with estrogen receptor (ER), Grade and NPI were used to build k
      nearest neighbor (KNN) classifiers that predicted ER, Grade and NPI status in the
      test set with an average misclassification rate of 24.7, 25.7 and 35.7%,
      respectively. These data raise the prospect of generating a molecular taxonomy of
      breast cancer based on copy number profiling using tumor DNA, which may be more
      generally applicable than expression microarray analysis.

PMID- 17001318
TI  - The kinase-inhibitory domain of p21-activated kinase 1 (PAK1) inhibits cell cycle
      progression independent of PAK1 kinase activity.
AB  - p21-activated kinase 1 (PAK1) is a mediator of downstream signaling from the
      small GTPases Rac and Cdc42. In its inactive state, PAK1 forms a homodimer where
      two kinases inhibit each other in trans. The kinase inhibitory domain (KID) of
      one molecule of PAK1 binds to the kinase domain of its counterpart and keeps it
      inactive. Therefore, the isolated KID of PAK1 has been widely used to
      specifically inhibit and study PAK function. Here, we show that the isolated KID
      induced a cell cycle arrest with accumulation of cells in the G1 phase of the
      cell cycle with an inhibition of cyclin D1 and D2 expression. This cell cycle
      arrest required the intact KID and was also induced by a mutated KID unable to
      block PAK1 kinase activity. Furthermore, the KID-induced cell cycle arrest could
      not be rescued by the expression of a constitutively active PAK1-T423E mutant,
      concluding that this arrest occurs independently of PAK1 kinase activity. Our
      results suggest that PAK1 through its KID inhibits cyclin D expression and
      thereby enforces a cell cycle arrest. Our results also call for serious
      precaution in the use of KID to study PAK function.

PMID- 17001319
TI  - HRPAP20: a novel calmodulin-binding protein that increases breast cancer cell
      invasion.
AB  - We previously reported the identification of HRPAP20 (hormone-regulated
      proliferation-associated protein 20), a novel hormone-regulated, proliferation
      associated protein. In tumor cell lines, constitutive HRPAP20 expression enhanced
      proliferation and suppressed apoptosis, characteristics frequently associated
      with malignant progression. Here, we report that highly invasive breast cancer
      cell lines and human breast tumor specimens express elevated HRPAP20, which in
      transfection experiments in MCF-7 and MDA-MB-231 cells, increased invasion.
      Results from mechanistic studies revealed that HRPAP20 bound to calmodulin (CaM)
      via a conserved CaM-binding motif. Transfection of MCF-7 breast cancer cells with
      HRPAP20 harboring a mutated CaM-binding motif (HRPAP20K73A) inhibited its
      interaction with CaM and failed to increase invasion. Other experiments revealed
      that transfection with HRPAP20, but not HRPAP20K73A, increased secretion of
      matrix metalloproteinase-9 (MMP-9). Moreover, knockdown of HRPAP20 with small
      interfering RNA in MCF-7/HRPAP20 transfectants and wild-type MDA-MB-231 cells
      reduced invasion and inhibited secretion of MMP-9. Together these observations
      suggest that HRPAP20 may be an important regulator of breast tumor cell invasion
      by a CaM-mediated mechanism that leads to increased MMP-9 secretion. We conclude
      that dysregulation of HRPAP20 expression in tumor cells may contribute to the
      observed phenotypic changes associated with breast cancer progression.

PMID- 17001320
TI  - Identification of novel VHL targets that are associated with the development of
      renal cell carcinoma.
AB  - von Hippel-Lindau (VHL) disease is a dominantly inherited family cancer syndrome
      characterized by the development of retinal and central nervous system
      haemangioblastomas, renal cell carcinoma (RCC) and phaeochromocytoma. Specific
      germline VHL mutations may predispose to haemangioblastomas, RCC and
      phaeochromocytoma to a varying extent. Although dysregulation of the hypoxia
      inducible transcription factor-2 and JunB have been linked to the development of
      RCC and phaeochromocytoma, respectively, the precise basis for genotype-phenotype
      correlations in VHL disease have not been defined. To gain insights into the
      pathogenesis of RCC in VHL disease we compared gene expression microarray
      profiles in a RCC cell line expressing a Type 1 or Type 2B mutant pVHL (RCC
      associated) to those of a Type 2A or 2C mutant (not associated with RCC). We
      identified 19 differentially expressed novel VHL target genes linked to RCC
      development. Eight targets were studied in detail by quantitative real-time
      polymerase chain reaction (three downregulated and five upregulated by wild-type
      VHL) and for six genes the effect of VHL inactivation was mimicked by hypoxia
      (but hypoxic-induction of smooth muscle alpha-actin 2 was specific for a RCC cell
      line). The potential role of four RCC-associated VHL target genes was assessed in
      vitro. NB thymosin beta (TMSNB) and proteinase-activated receptor 2 (PAR2) (both
      downregulated by wt pVHL) increased cell growth and motility in a RCC cell line,
      but aldehyde dehydrogenase (ALDH)1 and ALDH7 had no effect. These findings
      implicate TMSNB and PAR2 candidate oncogenes in the pathogenesis of VHL
      associated RCC.

PMID- 17001321
TI  - Interleukin-18 is a critical factor for vascular endothelial growth factor
      enhanced migration in human gastric cancer cell lines.
AB  - Cell migration and angiogenesis are key steps in tumor metastasis. However, the
      mechanism of migration regulated by vascular endothelial growth factor (VEGF), a
      potent regulator of angiogenesis, is not completely understood. This study
      examined the relationship between VEGF and migration, along with the mechanism
      involved in the VEGF-regulated migration of human gastric cancer cells. The level
      of cell migration was increased by recombinant human (rh)VEGF-165 in the VEGF
      receptor-2-expressing SNU-601 cells. Interleukin (IL)-18 is associated with the
      malignant progression of tumors. Accordingly, this study examined the effect of
      IL-18 on the migration of cancer cells in order to identify the factors involved
      in VEGF-enhanced migration. Inhibiting IL-18 markedly reduced the level of VEGF
      enhanced migration, and IL-18 increased cell migration directly through
      filamentous-actin polymerization and tensin downregulation. It was confirmed that
      rhVEGF-165 increased IL-18 production significantly. An antioxidant and an
      extracellular signal-regulated kinase (ERK)1/2-specific inhibitor blocked rhVEGF
      165-enhanced IL-18 production. Accordingly, rhVEGF-165 increased the generation
      of region of interest (ROI) and activated the ERK1/2 pathway. These results
      suggest that rhVEGF-165 enhances IL-18 production via the generation of ROI and
      ERK1/2 phosphorylation, which results in the increased migration of gastric
      cancer cells.

PMID- 17001322
TI  - Peripapillary atrophy in elderly Chinese in rural and urban Beijing.
AB  - PURPOSE: To determine peripapillary atrophy in elderly Chinese in an urban and
      rural regions of Beijing. METHODS: The Beijing Eye Study a population-based,
      cross-sectional cohort study, included 4,439 subjects out of 5,324 subjects who
      were asked to participate (response rate 83.4%). Mean age was 56.2+/-10.6 years
      (range, 40-101 years). Colour optic disc photographs (30 degrees ) were
      morphometrically examined. Peripapillary atrophy was divided into alpha zone and
      beta zone. RESULTS: Optic disc photographs were available for 4,027 (90.7%)
      subjects. Alpha zone and beta zone, respectively, were present in 2,867 (71.2%)
      subjects and 802 (19.9%) subjects, respectively, measuring 0.52+/-0.64 mm(2) and
      measuring 0.46+/-1.82 mm(2). Both zones were significantly widest and found
      significantly (P<0.001) most often in the temporal peripapillary region, followed
      by the temporal inferior region, the temporal superior region, and finally the
      nasal region. Size of both zones was significantly correlated with optic disc
      size (P<0.001), age (P<0.001), and myopic refractive error (P<0.001). Both zones
      increased significantly with decreasing uncorrected visual acuity (P<0.001) and
      decreasing best-corrected visual acuity (P<0.001). They did not vary
      significantly (P=0.10; and P=0.78) between male and female subjects. In
      multivariate analysis, the relationships between both zones and age, myopic
      refractive error, disc size, and uncorrected and best-corrected visual acuity
      remained statistically significant (P<0.001). CONCLUSIONS: Alpha zone and beta
      zone of peripapillary atrophy, respectively, occur in about 70 and 20%,
      respectively, of elderly Chinese. As peripapillary atrophy changes in
      glaucomatous optic neuropathy, these normative data may be helpful for glaucoma
      detection.

PMID- 17001323
TI  - En face optical coherence tomography of macular holes in high myopia.

PMID- 17001324
TI  - Light, dark, and melatonin: emerging evidence for the importance of melatonin in
      ocular physiology.
AB  - Melatonin is a hormone, which is mainly produced by the pineal gland, a vestigial
      eye. Rather than the rods and cones, it is a newly discovered subgroup of
      photosensitive retinal ganglion cells, which is responsible for mediating the
      light-dark cycles, thus regulating melatonin's secretion. One of the correlates
      of the circadian rhythm of melatonin release is the habitual sleep pattern.
      Patients with circadian rhythm sleep disorders, including some blind patients
      with no light-induced suppression of melatonin, benefit from melatonin treatment.
      Melatonin is synthesized in the retina, lens, ciliary body as well as other parts
      of the body. In this review, we discuss the physiological roles of melatonin in
      the eye, as well as the potential therapeutic avenues currently under study.

PMID- 17001325
TI  - Evidence for oxidative stress in lens epithelial cells in pseudoexfoliation
      syndrome.
AB  - PURPOSE: To investigate the oxidative status in lens epithelial cells of patients
      with pseudoexfoliation (PEX) syndrome. METHODS: Lens capsule samples obtained
      during cataract surgery of patients with PEX syndrome and normal age-matched
      control subjects were examined for changes in the levels of glutathione (GSH),
      glutathione disulphide (GSSG), protein concentration, and lipid peroxidation.
      Concentrations of GSH, GSSG, lipid peroxidation, and protein concentration were
      determined by specific fluorescent assays. RESULTS: This study shows a 2.2- and
      2.0-fold decrease in GSH and GSSG levels, respectively, in PEX lens epithelial
      lens compared with non-PEX lens epithelial cells, as well as a 2.5-fold increase
      in lipid peroxidation product malondialdehyde (MDA) levels. CONCLUSION: The
      increased MDA and decreased GSH levels indicate high oxidative stress. On the
      other hand, GSSG usually increases in cases of high-oxidative stress, but this is
      not always the case, as it may not always accumulate in cells. Our findings
      suggest a role for oxidative stress in the pathogenesis and the progression of
      PEX syndrome.

PMID- 17001326
TI  - A review of glaucoma treatment in Scotland 1994-2004.
AB  - OBJECTIVE: This study evaluated the changing trends in glaucoma management in
      Scotland between 1994 and 2004. METHODS: A retrospective analysis of national
      health statistics in Scotland from 1994 to 2004. The Scottish morbidity record
      was used to collect information on all episodes of trabeculectomy. Data on number
      of prescriptions were gathered for individual drugs and also for groups of active
      ingredient. The population likely to have glaucoma (PLG) was calculated from
      estimates of prevalence in individuals aged 40 years and older, based on
      published epidemiological studies. The outcome measures were trabeculectomy
      rates, corrected for population likely to be at risk of glaucoma (PLG), and
      prescribing volume and cost for glaucoma medications. RESULTS: Trabeculectomy
      rates have fallen by 67% from 46 per 1,000 PLG in 1994 to 15.4 per 1,000 PLG in
      2004. Over the same time period, the population likely to be at risk of glaucoma
      (PLG) increased by 16.6%. The cost of prescribing has increased by 122% over 11
      years compared with an increase in number of items per 1,000 PLG by 27.5%. In
      1994, beta-blockers accounted for 65.2% of prescribed drugs but by 2004 this had
      dropped to 33%. Since their introduction, the prescribing of prostaglandin
      analogues has increased rapidly and in 2004, they accounted for 39.4% of
      prescribed drugs. CONCLUSION: The increasing use of prostaglandin analogues has
      led to an increase in prescribing rates and a rapid increase in cost. At the same
      time, prescribing of beta-blockers has declined and trabeculectomy rates have
      fallen.

PMID- 17001327
TI  - Concentration of haemodynamic and inflammatory related cytokines in diabetic
      retinopathy.
AB  - AIM: There are changes in blood flow during the clinical stages of diabetic
      retinopathy with increasing leukostasis and secondary elaboration of cytokines.
      This study evaluated the vitreous concentrations of haemodynamic-related
      (endothelin-1 (ET-1) and nitric oxide (NO)), inflammatory and anti-inflammatory
      (interleukin-1 receptor antagonist, IL-1 Ra) cytokines in the diabetic patients
      (with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic
      retinopathy (PDR)), compared them with those of control patients (full thickness
      macular hole, FTMH) and correlated to macular structural indices. METHOD:
      Vitreous samples from five FTMH patients representing normal controls were
      analysed together with the vitreous samples of 15 patients with NPDR and five
      with PDR. The vitreous concentrations of nitrite (total NO), ET-1, and
      prostacyclin was determined using ELISA kits (R&D Systems, Minneapolis, MN, USA)
      according to the manufacturer's instructions. A sandwich luminescent immunoassay
      technique was used to determine IL-1beta and IL-1 Ra concentrations. RESULTS: In
      the different clinical groups, there were no differences in the vitreous NO and
      prostacyclin concentrations. In NPDR, the median ET-1 concentration (0.7 pg/ml SD
      +/-0.8 pg/ml) was significantly reduced (P<0.05), compared to PDR (6.35 pg/ml SD
      +/-0.6 pg/ml) and FTMH (3.6 pg/ml SD +/-0.14 pg/ml). Its concentration also
      positively correlated with foveal thickness and macular volume (P<0.05) in
      patients with NPDR and macular oedema. IL-1 beta was detected in PDR, and
      diabetic patients demonstrated a lower concentration of the anti-inflammatory
      cytokine IL-1 Ra. CONCLUSION: Reduced concentrations of ET-1 in NPDR may reflect
      the haemodynamic changes of NPDR. The IL-1 Ra concentration suggests a change in
      the anti-inflammatory environment of the diabetic retina.

PMID- 17001328
TI  - Spontaneous globe luxation and floppy eyelid syndrome in a patient with
      Hashimoto's disease.

PMID- 17001329
TI  - Duane syndrome associated with the Cat Eye syndrome: a case report.

PMID- 17001330
TI  - Fighting animal rights terrorism.

PMID- 17001332
TI  - Keeping the memories flowing.

PMID- 17001333
TI  - Turning by asymmetric actin.

PMID- 17001334
TI  - Hooking up new synapses.

PMID- 17001335
TI  - Intercellular miscommunication in polyglutamine pathogenesis.

PMID- 17001336
TI  - Walk the line: parietal neurons respect category boundaries.

PMID- 17001338
TI  - A genetics pioneer focused on child health challenges.

PMID- 17001339
TI  - From genes to behavior in developmental dyslexia.
AB  - All four genes thus far linked to developmental dyslexia participate in brain
      development, and abnormalities in brain development are increasingly reported in
      dyslexia. Comparable abnormalities induced in young rodent brains cause auditory
      and cognitive deficits, underscoring the potential relevance of these brain
      changes to dyslexia. Our perspective on dyslexia is that some of the brain
      changes cause phonological processing abnormalities as well as auditory
      processing abnormalities; the latter, we speculate, resolve in a proportion of
      individuals during development, but contribute early on to the phonological
      disorder in dyslexia. Thus, we propose a tentative pathway between a genetic
      effect, developmental brain changes, and perceptual and cognitive deficits
      associated with dyslexia.

PMID- 17001340
TI  - Time to give up on a single explanation for autism.
AB  - We argue that there will be no single (genetic or cognitive) cause for the
      diverse symptoms defining autism. We present recent evidence of behavioral
      fractionation of social impairment, communication difficulties and rigid and
      repetitive behaviors. Twin data suggest largely nonoverlapping genes acting on
      each of these traits. At the cognitive level, too, attempts at a single
      explanation for the symptoms of autism have failed. Implications for research and
      treatment are discussed.

PMID- 17001341
TI  - Fragile X syndrome and autism at the intersection of genetic and neural networks.
AB  - Autism, an entirely behavioral diagnosis with no largely understood etiologies
      and no population-wide biomarkers, contrasts with fragile X syndrome (FXS), a
      single-gene disorder with definite alterations of gene expression and neuronal
      morphology. Nevertheless, the behavioral overlap between autism and FXS suggests
      some overlapping mechanisms. Understanding how the single-gene alteration in FXS
      plays out within complex genetic and neural network processes may suggest targets
      for autism research and illustrate strategies for relating autism to more
      singular genetic syndromes.

PMID- 17001342
TI  - What developmental disorders can tell us about the nature and origins of
      language.
AB  - Few areas in the cognitive sciences evoke more controversy than language
      evolution, due in part to the difficulty in gathering relevant empirical data.
      The study of developmental disorders is well placed to provide important new
      clues, but has been hampered by a lack of consensus on the aims and
      interpretation of the research project. We suggest that the application of the
      Darwinian principle of 'descent with modification' can help to reconcile much
      apparently inconsistent data. We close by illustrating how systematic analyses
      within and between disorders, suitably informed by evolutionary theory-and
      ideally facilitated by the creation of an open-access database-could provide new
      insights into language evolution.

PMID- 17001343
TI  - Sinorhizobium meliloti nifA mutant induces different gene expression profile from
      wild type in Alfalfa nodules.
AB  - Several studies have demonstrated that the Rhizobium nifA gene is an activator of
      nitrogen fixation acting in nodule bacteria. To understand the effects of the
      Sinorhizobium meliloti nifA gene on Alfalfa, the cDNA-AFLP technique was employed
      to study the changes in gene expression in nifA mutant nodules. Among the
      approximately 3,000 transcript-derived fragments, 37 had differential expression
      levels. These expression levels were subsequently confirmed by reverse Northern
      blot and RT-polymerase chain reaction. Sequence analyses revealed that 21 cDNA
      fragments corresponded to genes involved in signal communication, protein
      degradation, nutrient metabolism, cell growth and development.

PMID- 17001344
TI  - Cytochrome P450 1A2 is a target antigen in hepatitic graft-versus-host disease.

PMID- 17001345
TI  - The use of granulocyte colony-stimulating factor in volunteer blood and marrow
      registry donors.

PMID- 17001346
TI  - Impact on the cytomegalovirus (CMV) viral load by CMV-specific T-cell immunity in
      recipients of allogeneic stem cell transplantation.
AB  - Patients experience cytomegalovirus (CMV) reactivation after stem cell
      transplantation (SCT) and need repeated courses of pre-emptive therapy. Analysis
      of CMV-specific immunity might help to assess the need for antiviral therapy.
      Forty-eight patients were studied during the first 3 months after SCT. Peripheral
      blood lymphocytes were stimulated by CMV antigen, and interferon (INF)-gamma
      production by CD3+ and CD4+ T cells was analysed. Results were correlated to
      transplant factors and CMV disease. Patients with INF-gamma production by CD3+
      cells at 4 weeks after SCT had lower peak viral loads than patients with no such
      production (P=0.03). There was a similar tendency as regards CD4+ cells (P=0.09).
      Patients who underwent reduced-intensity conditioning (RIC) more frequently had
      CD3+ (48%) and CD4+ immunity (56%) 4 weeks after SCT compared with patients who
      received myeloablative conditioning (CD3+ 25%; CD4+ 35%). There was no effect of
      stem cell source, donor type or acute graft-versus-host disease. Three of 48
      patients developed CMV disease and none of them had detectable INF-gamma
      production. CMV-specific T-cell response is associated with a lower rate of CMV
      replication. RIC results in improved T-cell reconstitution. Recovery of CMV
      specific immunity might be delayed in patients with CMV disease. These
      observations suggest that detection of CMV-specific T-cells is useful in
      assessing the immunity against CMV.

PMID- 17001349
TI  - Oncogenic BRAF regulates beta-Trcp expression and NF-kappaB activity in human
      melanoma cells.
AB  - Mutational activation of BRAF is a frequent event in human malignant melanomas
      suggesting that BRAF-dependent signaling is conducive to melanoma cell growth and
      survival. Previously published work reported that melanoma cells exhibit
      constitutive anti-apoptotic nuclear factor kappaB (NF-kappaB) transcription
      factor activation triggered by proteolysis of its inhibitor IkappaB. IkappaB
      degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK)
      complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin
      ligase. Here, we report that melanocytes expressing a conditionally oncogenic
      form of BRAF(V600E) exhibit enhanced beta-Trcp expression, increased IKK activity
      and a concomitant increase in the rate of IkappaBalpha degradation. Conversely,
      inhibition of BRAF signaling using either a broad-spectrum Raf inhibitor (BAY 43
      9006) or by selective knock-down of BRAF(V600E) expression by RNA interference in
      human melanoma cells leads to decreased IKK activity and beta-Trcp expression,
      stabilization of IkappaB, inhibition of NF-kappaB transcriptional activity and
      sensitization of these cells to apoptosis. Taken together, these data support a
      model in which mutational activation of BRAF in human melanomas contributes to
      constitutive induction of NF-kappaB activity and to increased survival of
      melanoma cells.

PMID- 17001352
TI  - Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues
      for associations with human leukocyte class I and II antigens.
AB  - Clozapine-induced agranulocytosis (CA) is still among the least understood
      adverse drug reactions in psychopharmacology. In particular, its genetic
      background is far from being clarified. Within the framework of a case-control
      study, we performed human leukocyte antigen (HLA) genotyping and haplotype
      analyses in 42 non-Jewish Caucasian schizophrenic patients (N=42) suffering from
      CA and 75 non-Jewish Caucasian schizophrenic patients treated with clozapine
      without developing CA. While controlling for age (P<0.0001) and sex (P=0.835),
      testing of the alleles from both HLA-loci resulted in borderline results for Cw2
      (P=0.085, odds ratio (OR)=0.36, 95% confidence interval (CI): 0.08-1.23), Cw7
      (P=0.058, OR=2.0, 95% CI: 0.87-4.63) and DRB5*0201 (P=0.005, adjusted OR=22.15).
      For haplotype analysis, we obtained significant association results with CA for
      the two-locus haplotypes HLA-Cw-B (P=0.022) and HLA-DRB5-DRB4 (P=0.050), and for
      the three-locus haplotype HLA-Cw-B-DRB5 (P=0.030). The complex nature of CA
      implies that many genes might play a role, but currently, only HLA associations
      with CA are identified as clinically relevant.

PMID- 17001353
TI  - IMPDH1 promoter mutations in a patient exhibiting azathioprine resistance.
AB  - Around 9% of inflammatory bowel disease (IBD) patients are resistant to
      azathioprine. We hypothesized that these patients may carry mutations within
      inosine-5'-monophosphate dehydrogenase (IMPDH). To test this hypothesis, we
      screened 20 azathioprine-resistant patients for variations in the two IMPDH genes
      (IMPDH1 and IMPDH2) using dHPLC and DNA sequencing. A 9 bp insertion within the
      IMPDH1 P3 promoter was found in a patient exhibiting severe azathioprine
      resistance. The insertion is predicted to abolish a cAMP-response element (CRE)
      and was found to significantly reduce IMPDH1 P3 promoter activity in a luciferase
      reporter gene assay (P-value <0.001). This in vitro assay suggests the variant
      promoter has altered function in vivo and consequently may have contributed to
      the thiopurine resistance observed in this patient. The absence of functional
      variants within the other patients indicates that if IMPDH genetic variability
      contributes to azathioprine resistance it does so infrequently.

PMID- 17001354
TI  - [Cancer research new era].

PMID- 17001355
TI  - [Bone metastases].
AB  - Bone metastases represent a devastating clinical problem in the most frequent
      neoplasies, especially in multiple myeloma, tumours breast, prostate and lung.
      The consequences include pain which is refractory to conventional analgesics,
      osteolysis often leading to bone-marrow compression and pathological fractures,
      and metabolic disorders. Recent advances in diagnosis using imaging techniques as
      well as different biochemical techniques have helped accurate diagnosis and
      follow-up. The increase in survival has improved through a multimodal approach
      combining, inhibition of osteolysis, with prophylactic orthopaedic surgery and
      radiation therapy. Recent advances in basic research have determined the
      molecular metastatic that can predict its proclivity to metastasize. Basic
      research will improve understanding of the basic mechanisms and lead to the
      clarification of molecular targets that will help in the development of medicines
      capable of preventing, decreasing or blocking the metastatic process.

PMID- 17001356
TI  - [Reversion of atracurium and vecuronium residual nondepolarising neuromuscular
      blockade with low doses of neostigmine].
AB  - OBJECTIVES: To assess the effectiveness of low doses of neostigmine in the
      reversion of residual non-polarising neuromuscular blockade (RNMB). MATERIAL AND
      METHODS: The work involved one hundred and nineteen adult patients, ASA I-III,
      anaesthetised with fentanyl, thiopental, O2-N2O-isoflurane and atracurium (n=62)
      or vecuronium (n=57). RNMB was monitored with continuous electromyography of
      adductor pollicis with TOF stimulation. When TOF-Ratio (TR) < 75%, neostigmine
      0.035, 0.03, 0.025 or 0.02 mg/kg (and atropine 0.0175, 0.015, 0.0125 or 0.01
      mg/kg) were administrated based on the degree of NMB (0-1, 2, 3 or 4) to TOF
      stimulation respectively, registering the time to achieve TR > 75% and secondary
      effects. RESULTS: Both groups were homogeneous. Twenty-five point eight percent
      (25.8%) (group A) and 21.1% (group V) presented TR>75% at the end of surgery,
      while 11.3% and 19.2% showed TR < 75% with 0-1 responses, 6.5% and 11.5% 2
      responses, 4.8% and 7.6% 3 responses, and 51.6% and 50% 4 responses to TOF
      stimulation in groups A or V respectively. All patients who received neostigmine
      presented TR > 75% in 10.5+/-7 (group A) and 10.3+/-6.4 min. (group V). A
      predominance of secondary effects in the atracurium group was observed (p=0.027),
      basically due to excessive salivation, nausea and vomiting. There were no cases
      of RNMB. CONCLUSIONS: The reversion of the residual neuromuscular blockade of
      atracurium or vecuronium with low doses of neostigmine and atropine adjusted to
      the degree of RNMB is effective even in deep blockades, reducing the risk of
      secondary effects.

PMID- 17001357
TI  - [Clinical profile and impact of the unscheduled return to Emergency Department by
      elders].
AB  - BACKGROUND: The characteristics of patients aged 65 years and over that return to
      the Emergency Department (ED) have not been sufficiently analysed. The aim of
      this study is to determine the differentiating elements of the elderly that
      return to ED and evaluate the impact on them of such a return. METHODS:
      Descriptive study where the unit of analysis is the unscheduled return to ED. The
      analysis of data begins with a description of the entire sample. After that,
      comparisons are made between the elderly and patients aged under 65 years that
      return, and between the elderly that return and those that do not return. The
      significance level for comparison tests is p< or =0.05. RESULTS: Sixty-one per
      cent of the reasons for the first visit by the elderly was because of
      neurological alterations (p<0,001). Only 22% of them had been attended by senior
      doctors on their first visit (p=0,001). When they returned to ED, 63% of them
      were admitted to hospital; in contrast to 28% of younger patients (p<0,001).
      CONCLUSIONS: There are differences between the elderly patients that return and
      those who do not, and also with respect to young adults. The impact of return on
      this group of patients is reflected in the high rates of admission to hospital.
      An adaptation of resources to the special needs of this type of user in ED would
      be advisable.

PMID- 17001358
TI  - [Hormones used as ergogenics: present state of the question].
AB  - Sporting competition in our society has become the spectacle that mobilises and
      brings together the greatest number of people throughout the world, with the
      corresponding cultural and economic influence that this implies. As a result, the
      desire for athletic prowess has led sportspersons to undergo intense training
      programs and to consume substances that improve their performance, at times
      having recourse to doping techniques. At present, doping is the result of a
      combination of social, individual, physiological and cultural factors, which
      affect not only professional, but also amateur sportspeople. In order for the
      control and eradication of doping to be efficient, it is necessary to understand
      the problem and the substances that are most employed, amongst which special
      mention is merited by hormonal substances due to the complexity of detecting them
      and their possible repercussions on health.

PMID- 17001359
TI  - [Urinary incontinence].
AB  - Urinary incontinence, understood as any involuntary loss of urine, constitutes an
      important medical and social problem. It can be classified as stress urinary
      incontinence, urgent urinary incontinence or mixed urinary incontinence. The
      proportions of these three types of urinary incontinence are difficult to
      establish and vary notably between sources, but they might be about 40, 33 and
      20% respectively. Its diagnosis requires a correct clinical history and physical
      exploration, together with some complementary explorations. The first therapeutic
      step consists of hygienic-dietary measures and behaviour modification techniques.
      Pharmacological treatment is specific for each type of urinary incontinence,
      using anticholinergics and inhibitors of serotonin reuptake. Finally, different
      surgical techniques have a role in cases where conservative treatments fail or
      when dealing with severe urinary incontinence.

PMID- 17001360
TI  - [Interaction between medicines and medicinal plants].
AB  - In recent years there has been a notable increase in the consumption of medicinal
      plants in Spanish society. This might be due to the fact that in some cases they
      have shown themselves to be efficient in treating certain pathologies and to the
      erroneous perception that these products are innocuous. Medicinal plants behave
      as authentic medicines since the chemical substances of which they are formed can
      have a biological activity in humans. For this reason, their joint administration
      with "conventional medicines" can produce variations in the magnitude of the
      effect. This type of interaction, just like those produced between two or more
      medicines, can produce pharmacokinetic mechanisms if they affect the processes of
      absorption, distribution, metabolism and excretion, or pharmacodynamic mechanisms
      if they affect the result of the pharmacological action. In the medical
      literature there are few articles and notifications of cases concerning the
      adverse effects and interactions that affect medicinal plants, which probably
      reflects an under-notification of these phenomena. If we add to this the lack of
      experimental data and controlled studies, perception of their prevalence is
      difficult or nearly impossible. This article sets out, in an order that will be
      explained later, the findings of an exhaustive review of the medical literature
      with the aim of making its existence known to the reader, without going into
      other considerations, such as the degree of evidence for example, which will be
      the subject of forthcoming articles.

PMID- 17001361
TI  - [Law courts and clinical documentation].
AB  - Background. Until 2004, requests for clinical documentation proceeding from the
      Judicial Administration on Specialist Care of Pamplona were received in six
      different centres and were processed independently, with different procedures,
      and documents were even sent in duplicate, with the resulting work load. This
      article describes the procedure for processing requests for documentation
      proceeding from the Law Courts and analyses the requests received. Methods. A
      circuit was set up to channel the judicial requests that arrived at the
      Specialist Health Care Centres of Pamplona and at the Juridical Regime Service of
      the Health System of Navarra-Osasunbidea, and a Higher Technician in Health
      Documentation was contracted to centralise these requests. A proceedings protocol
      was established to unify criteria and speed up the process, and a database was
      designed to register the proceedings. Results. In the course of 2004, 210
      requests for documentation by legal requirement were received. Of these, 24 were
      claims of patrimonial responsibility and 13 were requested by lawyers with the
      patient's authorisation. The most frequent jurisdictional order was penal
      (43.33%). Ninety-three point one five percent (93.15%) of the requests proceeded
      from law courts in the autonomous community of Navarra. The centre that received
      the greatest number of requests was the "Principe de Viana" Consultation Centre
      (33.73%).The most frequently requested documentation was a copy of reports (109)
      and a copy of the complete clinical record (39). On two occasions the original
      clinical record was required. The average time of response was 6.6 days.
      Conclusions. The centralisation of administration has brought greater agility to
      the process and homogeneity in the criteria of processing. Less time is involved
      in preparing and dispatching the documentation, the dispatch of duplicate
      documents is avoided, the work load has been reduced and the dispersal of
      documentation is avoided, a situation that guarantees greater privacy for the
      patient.

PMID- 17001362
TI  - [Intra-articular dislocation of patella].
AB  - The case of a patient aged 73 years who, following an accidental fall on a
      staircase, suffered an acute intraarticular dislocation in the left knee-cap is
      presented. This exceptional dislocation presented incarceration of the proximal
      kneecap pole in the femoral intercondylar groove. A reduction was carried out
      under general anaesthetic due to pain and muscular contraction in the attempts at
      reduction without anaesthetic. We made a surgical check that ruled out associated
      lesions to the extensor apparatus, soft parts, joint structures and osteophytes.
      The patient presented advanced arthrosis, above all femoral-patellar. Following
      two weeks of immobilisation, the patient restarted mobility. There has been no
      relapse or other type of complication.

PMID- 17001363
TI  - [Negative pressure pulmonary edema: 3 case reports].
AB  - Negative pressure pulmonary edema is a complication, described since 1977, caused
      by upper airway obstruction in both children and adults. Although its
      aetiopathogeny is multifactorial, especially outstanding is excessive negative
      intrathoracic pressure caused by the forced spontaneous inspiration of a patient
      against a closed glottis, that causes high arteriole and capillary fluid
      pressures that favor transudation into the alveolar space The resulting pulmonary
      edema can appear a few minutes after the obstruction of the airway or in a
      deferred way after several hours. The clinical manifestations are potentially
      serious, but normally respond well to treatment with supplemental oxygen,
      positive pressure mechanical ventilation and diuretics. Diagnostic suspicion is
      important for acting promptly. We report three clinical cases with acute negative
      pressure pulmonary edema.

PMID- 17001364
TI  - [Spontaneous pneumomediastinum].
AB  - Spontaneous pneumomediastinum (defined by the presence of free air in the
      mediastinum) is an infrequent entity that is presented in the absence of diseases
      or precipitating factors. It generally affects young and healthy males. Thoracic
      pain, dyspnea, or both, are the most frequent symptoms. Other signs and symptoms
      are subcutaneous emphysema and Hamman's sign. Simple radiography of the thorax
      allows for the diagnosis in a high percentage of patients. Conservative treatment
      is indicated in these patients and has a favourable prognosis. Relapses are
      infrequent.

PMID- 17001365
TI  - Gain-guided solitons in dispersion-managed fiber lasers with large net cavity
      dispersion.
AB  - Gain-guided solitons are experimentally observed in dispersion-managed fiber
      lasers with large net positive group-velocity dispersion. It is shown that
      formation of the soliton is a robust feature of the lasers. Numerical simulations
      also confirmed the experimental results.

PMID- 17001366
TI  - Optical inclinometer based on a single long-period fiber grating combined with a
      fused taper.
AB  - A new concept to measure rotation angles based on a fiber-optic modal Mach
      Zehnder interferometer is demonstrated by using a nonadiabatic taper cascaded
      with a long-period fiber grating. Information about the magnitude of the rotation
      angle can be obtained from the measurement of the interference pattern
      visibility, and under certain conditions it is also possible to obtain the sign
      of the rotation angle from the induced phase variation in the fiber
      interferometer.

PMID- 17001367
TI  - Intensity noise reduction in a multiwavelength distributed Bragg reflector fiber
      laser.
AB  - Noise reduction in a multiwavelength distributed Bragg reflector fiber laser was
      demonstrated. A 20 dB reduction of in-phase intensity noise was achieved by using
      negative feedback to modulate the drive current of the laser pump diode.
      Strategies for reducing antiphase noise components are discussed.

PMID- 17001368
TI  - Bismuth-doped-glass optical fibers--a new active medium for lasers and
      amplifiers.
AB  - Optical fibers with bismuth-doped silicate and germanate glass cores were
      fabricated by the modified chemical vapor deposition technique (solution and
      vapor-phase Bi incorporation). The fibers revealed an efficient luminescence with
      a maximum in the 1050-1200 nm spectral range, FWHM up to 200 nm, and a lifetime
      of the order of 1 ms.

PMID- 17001369
TI  - Generation of radially polarized mode in Yb fiber laser by using a dual conical
      prism.
AB  - For the first time to our knowledge, a radially polarized beam is generated in an
      Yb-doped multimode double-clad fiber laser by using an intracavity dual conical
      prism. Up to 6.2 mW of output power is obtained from a 2 m long gain fiber with
      7.4% slope efficiency. This research opens a new window to obtaining a radially
      polarized beam directly from an active fiber.

PMID- 17001370
TI  - Improving accuracy by subpixel smoothing in the finite-difference time domain.
AB  - Finite-difference time-domain (FDTD) methods suffer from reduced accuracy when
      modeling discontinuous dielectric materials, due to the inhererent discretization
      (pixelization). We show that accuracy can be significantly improved by using a
      subpixel smoothing of the dielectric function, but only if the smoothing scheme
      is properly designed. We develop such a scheme based on a simple criterion taken
      from perturbation theory and compare it with other published FDTD smoothing
      methods. In addition to consistently achieving the smallest errors, our scheme is
      the only one that attains quadratic convergence with resolution for arbitrarily
      sloped interfaces. Finally, we discuss additional difficulties that arise for
      sharp dielectric corners.

PMID- 17001371
TI  - Buffered Fourier domain mode locking: Unidirectional swept laser sources for
      optical coherence tomography imaging at 370,000 lines/s.
AB  - We describe buffered Fourier domain mode locking (FDML), a technique for
      tailoring the output and multiplying the sweep rate of FDML lasers. Buffered FDML
      can be used to create unidirectional wavelength sweeps from the normal
      bidirectional sweeps in an FDML laser without sacrificing sweep rate. We also
      investigate the role of the laser source in dynamic range versus sensitivity
      performance in optical coherence tomography (OCT) imaging. Unidirectional sweep
      rates of 370 kHz over a 100 nm range at a center wavelength of 1300 nm are
      achieved. High-speed, swept-source OCT is demonstrated at record speeds of up to
      370,000 axial scans per second.

PMID- 17001372
TI  - Imaging theory of an aplanatic system with a stratified medium based on the
      method for a vector coherent transfer function.
AB  - A simple formalism relating image fields to object fields, similar to that of the
      scalar and paraxial case, is presented for an aplanatic system obeying the sine
      condition, which shows that the vector plane-wave spectrum of image fields is
      equal to the product of the vector coherent transfer function due to the x- and y
      polarized point electric field source and the scalar spectrum of the
      corresponding transverse object fields. Utilizing this formula and dyadic Green's
      function, a rigorous imaging theory of an aplanatic system for the point electric
      current source through a stratified medium is readily developed.

PMID- 17001373
TI  - Low-order aberration sensitivity of an optical vortex coronagraph.
AB  - We describe a high-contrast imaging technique capable of directly measuring light
      from a terrestrial planet by using a vortex mask of topological charge m = 5. We
      demonstrate that this technique is relatively insensitive to low-order
      aberrations and compare its performance to that of a band-limited Lyot
      coronagraph.

PMID- 17001374
TI  - Hybrid division of aperture/division of a focal-plane polarimeter for real-time
      polarization imagery without an instantaneous field-of-view error.
AB  - The direct, instantaneous measurement of the Stokes parameters of optical
      radiation is not possible using only a single detector. To infer the Stokes
      parameters in an image, the optical intensity must be modulated in time, space,
      or spectral characteristics and multiple measurements must be made on a pixel-by
      pixel basis across the scene. Most existing imaging polarimetry strategies
      generally suffer from either spatial or temporal misregistration. Those
      strategies that do not suffer from misregistration have severe restrictions
      placed on the spectral properties of the illumination and/or optical system. A
      hybrid polarimeter is proposed that can be used for broadband imaging
      applications that, in principle, can be made without any temporal or spatial
      misalignment and that does not require detailed knowledge of the spectral
      properties of the radiation. The strategy uses arrays of microlenses and
      micropolarizers to create a high-resolution spatial array of nonimaging division
      of aperture polarimeters.

PMID- 17001375
TI  - Ultrafast laser waveguide writing: Lithium niobate and the role of circular
      polarization and picosecond pulse width.
AB  - For the first time to our knowledge, ultrafast laser writing has generated room
      temperature stable guided-wave optics in bulk lithium niobate for the
      telecommunication spectrum. Among a seven-dimensional parameter space for
      waveguide optimization, two frequently overlooked parameters, pulse duration and
      polarization, were found to be key in overcoming undesired nonlinear optical
      responses imposed by this material. Single-mode waveguides were best formed with
      circularly polarized light having a relatively long pulse duration of
      approximately 1.0 ps. The waveguides were highly polarization dependent and
      guided in both telecommunication bands near 1300 and 1550 nm, exhibiting losses
      as low as 0.7 dB/cm.

PMID- 17001376
TI  - Comment on "Generation of 10(11) contrast 50 TW laser pulses".
AB  - We argue for a different physical interpretation of the results given in the
      recent Letter by Chvykov et al. [Opt. Lett.31, 1456 (2006)] in which a double
      nonlinear crystal scheme for cross-polarized wave generation is analyzed. We
      discuss the most important factors that explain the origin of the two-crystal
      scheme's increased efficiency, namely, the Kerr lensing effect and a Gouy phase
      shift. The position and orientation of the second crystal relative to the first
      one are unambiguously defined; related effects are illustrated by already
      published works on the subject.

PMID- 17001378
TI  - Simultaneous fluorometry and phosphorometry of Langendorff perfused rat heart: ex
      vivo animal studies.
AB  - Fluorescence imaging of intrinsic fluorophores of tissue is a powerful method to
      assess metabolic changes at the cellular and intracellular levels. At the same
      time, exogenous phosphorescent probes can be used to accurately measure
      intravascular tissue oxygenation. Heart failure is the leading cause of death in
      America. A rat heart can potentially model the human heart to study failures or
      other abnormalities optically. We report simultaneous fluorescence and
      phosphorescence measurements performed on a rat heart. We have used two different
      optical systems to acquire fluorescence signals of flavoprotein and nicotinamide
      adenine dinucleotide--the two intrinsic fluorophores of mitochondria--and the
      phosphorescence signal of an intravascular oxygen probe to extract intracellular
      and intravascular metabolism loads, respectively.

PMID- 17001379
TI  - Photoacoustic detection of metastatic melanoma cells in the human circulatory
      system.
AB  - Detection of disseminating tumor cells among patients suffering from various
      types and stages of cancer can function as an early warning system, alerting the
      physician of the metastatic spread or recurrence of the disease. Early detection
      of such cells can result in preventative treatment of the disease, while late
      stage detection can serve as an indicator of the effectiveness of
      chemotherapeutics. The prognostic value of exposing disseminating tumor cells
      poses an urgent need for an efficient, accurate screening method for metastatic
      cells. We propose a system for the detection of metastatic circulating tumor
      cells based on the thermoelastic properties of melanoma. The method employs
      photoacoustic excitation coupled with a detection system capable of determining
      the presence of disseminating cells within the circulatory system in vitro.
      Detection trials consisting of tissue phantoms and a human melanoma cell line
      resulted in a detection threshold of the order of ten individual cells, thus
      validating the effectiveness of the proposed mechanism. Results imply the
      potential to assay simple blood draws, from healthy and metastatic patients, for
      the presence of cancerous melanoma providing an unprecedented method for routine
      cancer screening.

PMID- 17001380
TI  - Real-time flow imaging by removing texture pattern artifacts in spectral-domain
      optical Doppler tomography.
AB  - We present a new, simple method to suppress texture pattern artifacts induced by
      the optical heterogeneity of tissues to improve the performance of flow imaging
      for real-time phase-resolved optical Doppler tomography. The method performs
      transverse scanning of the probe beam in the forward and then reverse directions,
      and it takes average of the spatial phase changes between them to obtain the
      final velocity image. It relies on the fact that the phase changes between
      successive axial scans due to the optical heterogeneity of the sample are time
      independent, while those due to the moving particles are time dependent. We
      experimentally demonstrate this method by real-time imaging of a flow phantom.

PMID- 17001381
TI  - Surface plasmon interferometric microscopy for three-dimensional imaging of
      dynamic processes.
AB  - A method, which we named surface plasmon interferometric microscopy, for real
      time displaying of the dynamic evolution of the refractive index (RI) of a sample
      in three-dimensions is demonstrated experimentally. The Fourier fringe analysis
      technique is employed to get the phase variations of the samples by demodulating
      the interference patterns captured by a CCD camera, and the 3D RI distribution
      can be obtained through numerical interpolation from the relation between the
      phase and the RI of the samples. Our method may provide an interesting way to
      monitor fast dynamics of physical, biological, and chemical processes in real
      time.

PMID- 17001382
TI  - Spectral broadening in Raman fiber lasers.
AB  - We present an analytical theory based on wave kinetic equations that describes a
      Raman fiber laser (RFL) generation spectrum. It is shown both theoretically and
      experimentally that the quasi-degenerate four-wave mixing between different
      longitudinal modes is the main broadening mechanism in the one-stage RFL at high
      powers. The shape and power dependence of the intracavity Stokes wave spectrum
      are in excellent quantitative agreement with predictions of the theory.

PMID- 17001383
TI  - Oblique interaction of spatial dark-soliton stripes in nonlocal media.
AB  - We report what we believe to be the first experimental observation of a large
      spatial lateral shift in the interaction of obliquely oriented spatial dark
      soliton stripes. We demonstrate by numerical simulations that this new effect can
      be attributed to the specific features of optical media with a nonlocal nonlinear
      response.

PMID- 17001384
TI  - Finite-dimensional model for defect-trapped light in planar periodic nonlinear
      structures.
AB  - We study the dynamics of 2D gap solitons (GSs) in Bragg resonant nonlinear
      (photonic) gratings in the presence of localized defects. Previous work [Stud.
      Appl. Math.115, 209 (2005)] explains the mechanism of trapping the GS-carried
      energy at a defect via a resonant energy transfer from the GS into defect modes.
      We derive a finite-dimensional model that describes the evolution of the defect
      trapped state as an interaction of linear defect modes and show that this model
      approximates the full dynamics very well in the regime when moderate amounts of
      GS energy are trapped.

PMID- 17001385
TI  - Microlens array diffuser for a light-emitting diode backlight system.
AB  - Microlens array (MLA) diffusers for light-emitting diode (LED) backlight systems
      have been developed. A high fill-factor photoresist mold for the MLA was
      fabricated using three-dimensional diffuser lithography, and the patterns were
      transferred to a nickel master mold for UV-curable polymer replication. The
      fabricated microlens had various paraboloidal profiles, and its aspect ratio was
      controlled from 1.0 to 2.1. The MLA diffuser showed a batwing radiation pattern
      with a radiation angle of 150 degrees. The fabricated MLA diffuser may greatly
      enhance the color-mixing characteristics of LED backlight systems and help reduce
      the number of LEDs required.

PMID- 17001386
TI  - Unique optical properties of anisotropic helical structures in a Fabry-Perot
      cavity.
AB  - Anisotropic helical structures in Fabry-Perot (FP) cavities are shown to exhibit
      unique properties. The FP peaks are unpolarized, consisting of doublets
      corresponding to Bloch-Lyaponov eigenwaves with increased splitting as the local
      anisotropy increases and as they become closer to the photonic bandgap. The Bragg
      type selective reflection peak existing in a free-cavity sample is inhibited when
      the helical medium is inside a cavity, and it has no effect on the cavity modes.
      Hence the unique characteristics are obtained even with a single period of the
      helix, and consequently thin films of helical liquid crystals can be used to
      build fast tunable polarization insensitive FP filters.

PMID- 17001387
TI  - Enhancement of surface plasmons in an Ag aggregate by optical gain in a
      dielectric medium.
AB  - We have observed the compensation of loss in a metal by a gain in a dielectric
      medium in the mixture of an Ag aggregate and a Rhodamine 6G dye. The demonstrated
      sixfold enhancement of the Rayleigh scattering is the evidence of the enhancement
      of the surface-plasmon resonance. The reported experimental observation
      facilitates many applications of nanoplasmonics.

PMID- 17001388
TI  - Can two planar sources with the same sets of Stokes parameters generate beams
      with different degrees of polarization?
AB  - It is shown that two stochastic electromagnetic beams that propagate from the
      source plane z = 0 into the half-space z > 0 may have different degrees of
      polarization throughout the half-space, even though they have the same sets of
      Stokes parameters in the source plane. This fact is due to a possible difference
      in the coherence properties of the field in that plane, but other reasons are
      also possible. The result is illustrated by an example.

PMID- 17001389
TI  - Complete far-field asymptotic series for free fields.
AB  - The closed form of the complete far-field asymptotic series is provided for the
      scalar and electromagnetic monochromatic fields in free space whose angular
      spectrum is smooth over the sphere of directions. The first few terms of this
      series are also shown to give corrections to the Fraunhofer diffraction formula.
      The application of this series is illustrated with two examples corresponding to
      a highly focused radially polarized field and to the scalar diffraction from a
      circular aperture.

PMID- 17001390
TI  - Synthetic aperture laser optical feedback imaging using galvanometric scanning.
AB  - We describe a new one-dimensional synthetic aperture imaging laser radar (ladar)
      using the resonant sensitivity of a microchip laser to frequency-shifted optical
      feedback and galvanometric scanning of the target under investigation. In our
      experiment, the laser is both the source and the detector, providing optical
      amplification with self-aligned heterodyne detection. By using galvanometric
      scanning, we achieve an along-track spatial resolution better than the
      diffraction limit.

PMID- 17001391
TI  - Simultaneous forward- and backward-hemisphere elastic-light-scattering patterns
      of respirable-size aerosols.
AB  - Two-dimensional angular optical scattering (TAOS) patterns of aerosols are
      measured simultaneously from the forward hemisphere 15 degrees < theta < 90
      degrees as well as the backward hemisphere 90 degrees < theta < 165 degrees
      (detecting 63% of the 4pi sr of scattered light) by using an ellipsoidal
      reflector and an intensified CCD detector. TAOS patterns were obtained from
      polystyrene-latex spheres (individuals and aggregates) and from single Bacillus
      subtilis spores. These information-rich patterns, measured with a single laser
      pulse for individual particles on the fly, suggest that forward-TAOS and backward
      TAOS measurements may be used for rapid classification of single aerosol
      particles.

PMID- 17001392
TI  - Characterization of frequency-tripled nanosecond pulsed Ti:sapphire laser
      injection seeded by a frequency-scanning cw Ti:sapphire laser by use of
      optogalvanic spectroscopy of silicon atoms.
AB  - The performance of a narrow-linewidth nanosecond pulsed deep-UV coherent light
      source consisting of a frequency-tripled nanosecond pulsed Ti:sapphire laser
      injection seeded by a frequency-scanning cw Ti:sapphire laser has been
      characterized by using optogalvanic spectroscopy of silicon atoms as a
      diagnostic. The envelope of the optogalvanic spectrum indicates the pure Doppler
      broadening of silicon atoms, which was estimated to be as broad as 4 GHz, without
      the broadening effect from the laser linewidth itself.

PMID- 17001393
TI  - Doppler-free saturated-absorption spectroscopy of CO2 at 4.3 microm by means of a
      distributed feedback quantum cascade laser.
AB  - We report the application of a cw distributed feedback quantum cascade laser to
      Lamb-dip spectroscopy of CO2 at 4.3 microm. With the laser operating in the free
      running mode, we observed the sub-Doppler profile of the P(28) line of the
      (0,1(1),0)->(0,1(1),1) hot band by implementing a pump-probe scheme and using
      wavelength modulation spectroscopy for highly sensitive detection of saturated
      absorption signals. We investigated the main limitations to the observation of a
      narrow resonance, with particular attention to the effect of the laser current
      noise. We determined the intrinsic laser emission width, which was found to be
      approximately 3.4 MHz (FWHM) for an observation time of approximately 200 ms.

PMID- 17001394
TI  - Pulse duration measurements of grazing-incidence-pumped high repetition rate Ni
      like Ag and Cd transient soft x-ray lasers.
AB  - We have measured the pulse duration of gain-saturated 13.9 nm Ni-like Ag and 13.2
      nm Ni-like Cd transient collisional lasers excited by grazing-incidence-pumping
      for several pumping conditions. High-resolution streak-camera measurements
      yielded FWHM pulse durations close to 5 ps for both lasers under optimum pumping
      conditions. The very high brightness and short pulse duration of these new high
      repetition tabletop soft x-ray lasers make them an attractive source for dynamic
      applications.

PMID- 17001395
TI  - Fiber-laser frequency combs with subhertz relative linewidths.
AB  - We investigate the comb linewidths of self-referenced, fiber-laser-based
      frequency combs by measuring the heterodyne beat signal between two independent
      frequency combs that are phase locked to a common cw optical reference. We
      demonstrate that the optical comb lines can exhibit instrument-limited, subhertz
      relative linewidths across the comb spectra from 1200 to 1720 nm with a residual
      integrated optical phase jitter of approximately 1 rad in a 60 mHz to 500 kHz
      bandwidth. The projected relative pulse timing jitter is approximately 1 fs. This
      performance approaches that of Ti:sapphire frequency combs.

PMID- 17001396
TI  - Temporal resolution limits of time-to-frequency transformations.
AB  - Time-to-frequency converters are devices that transfer the intensity of a light
      pulse to its spectrum. The two architectures of these converters are studied: a
      dispersive line followed by a phase modulator and a single time lens operating in
      the spectral Fraunhofer regime. These two configurations are shown not to be
      equivalent in general: the first one provides an incoherent time-to-frequency
      mapping, whereas the second depends on the degree of coherence of the pulse. In
      this case, the recorded spectrum is the intensity of a partially coherent
      residually dispersed pulse, and the spectral Fraunhofer condition is the
      requirement of negligible residual dispersion. Converters operated outside the
      spectral Fraunhofer limit can achieve a subpicosecond resolution with moderate
      time-lens phase factors. Their use for pulse characterization is briefly
      analyzed.

PMID- 17001397
TI  - A swash-backwash model of the single epidemic wave.
AB  - While there is a large literature on the form of epidemic waves in the time
      domain, models of their structure and shape in the spatial domain remain poorly
      developed. This paper concentrates on the changing spatial distribution of an
      epidemic wave over time and presents a simple method for identifying the leading
      and trailing edges of the spatial advance and retreat of such waves. Analysis of
      edge characteristics is used to (a) disaggregate waves into 'swash' and
      'backwash' stages, (b) measure the phase transitions of areas from susceptible,
      S, through infective, I, to recovered, R, status (S --> I --> R) as dimensionless
      integrals and (c) estimate a spatial version of the basic reproduction number,
      R(0). The methods used are illustrated by application to measles waves in Iceland
      over a 60-year period from 1915 to 1974. Extensions of the methods for use with
      more complex waves are possible through modifying the threshold values used to
      define the start and end points of an event.

PMID- 17001398
TI  - Capsule endoscopy: specifics for enhanced performance--Part II.

PMID- 17001399
TI  - The life, achievements and legacy of a great Canadian investigator: Professor
      Boris Petrovich Babkin (1877-1950).
AB  - The present paper reviews the life and achievements of Professor Boris Petrovich
      Babkin (MD DSc LLD). History is only worth writing about if it teaches us about
      the future; therefore, this historical review concludes by describing what
      today's and future gastrointestinal physiologists could learn from Dr Babkin's
      life. Dr Babkin was born in Russia in 1877. He graduated with an MD degree from
      the Military Medical Academy in St Petersburg, Russia, in 1904. Not being
      attracted to clinical practice, and after some hesitation concerning whether he
      would continue in history or basic science of medicine, he entered the laboratory
      of Professor Ivan Petrovich Pavlov. Although he maintained an interest in
      history, in Pavlov's exciting environment he became fully committed to physiology
      of the gastrointestinal system. He advanced quickly in Russia and was Professor
      of Physiology at the University of Odessa. In 1922, he was critical of the
      Bolshevik revolution, and after a short imprisonment, he was ordered to leave
      Russia. He was invited with his family by Professor EH Starling (the discoverer
      of secretin) to his department at University College, London, England. Two years
      later, he was offered a professorship in Canada at Dalhousie University, Halifax,
      Nova Scotia. After contributing there for four years, he joined McGill
      University, Montreal, Quebec, in 1928 as Research Professor. He remained there
      for the rest of his career. Between 1940 and 1941, he chaired the Department, and
      following retirement, he remained as Research Professor. At the invitation of the
      world-famous neurosurgeon, Wilder Penfield, Dr Babkin continued as Research
      Fellow in the Department of Neurosurgery until his death in 1950 at age 73. His
      major achievements were related to establishing the concept of brain-gut-brain
      interaction and the influence of this on motility, as well as on interface of
      multiple different cells, nerves and hormones on secretory function. He had a
      major role in the rediscovery of gastrin. He established a famous school of
      gastrointestinal physiologists at McGill University. He supported his trainees
      and helped them establish their careers. He received many honors: a DSc in
      London, England, and an LLD from Dalhousie University. Most importantly, he was
      the recipient of the Friedenwald Medal of the American Gastroenterological
      Association for lifelong contributions to the field. Dr Babkin taught us his
      philosophical aspect of approaching physiology, his devotion to his disciples and
      his overall kindness. Most importantly, he has proven that one can achieve
      international recognition by publishing mainly in Canadian journals. He is an
      example to follow.

PMID- 17001400
TI  - Elderly patients are at greater risk of cytopenia during antiviral therapy for
      hepatitis C.
AB  - The results of antiviral therapy for hepatitis C virus (HCV) have improved
      recently with the use of pegylated interferon (PEG-IFN)/ribavirin (RBV)
      combination therapy. At this point, most patients with chronic HCV remain
      untreated. Thus, it is anticipated that therapy will be more appealing and
      prescribed more broadly than in the past, including in patients considered
      marginal. AIM: To examine the effects of PEG-IFN-based antiviral therapy in
      elderly patients with chronic HCV. METHODS: The charts of patients treated with
      chronic HCV were reviewed. Patients were defined as elderly if they were 60 years
      of age or older. The control group consisted of patients younger than 60 years of
      age who were matched to the treated elderly patients based on sex, treating
      physician, prescribed treatment and intended prescribed treatment duration. The
      data recorded included end of treatment response, sustained virological response
      (SVR), adverse events, dose modification and withdrawal of therapy. RESULTS:
      Thirty of 147 (20.4%) elderly patients attending a hepatitis C clinic were
      treated. The average age of the elderly patients was 65+/-4 years. Forty-three
      per cent were men and 57% were women. Ten per cent received IFN monotherapy, 70%
      received a combination of IFN/RBV therapy and 20% received a combination of PEG
      IFN/RBV therapy. The overall response rates in the elderly patients compared with
      the younger patients was 46.7% versus 65.8% (P=0.11) for end of treatment
      response and 33.3% versus 51.2% (P=0.13) for SVR. The rate of dose modification
      was 50% in the elderly patients compared with 29% in the control group (P=0.08).
      Therapy was discontinued in 53% of the elderly compared with 34% of younger
      patients (P=0.17). The younger patients reported more side effects than elderly
      patients; although, there were more laboratory abnormalities (anemia,
      thrombocytopenia and neutropenia) in the elderly patients during therapy than in
      the younger group (0.93 per patient versus 0.49 per patient, P=0.01). CONCLUSION:
      Elderly patients with chronic HCV can be treated successfully. However, they are
      more at risk to develop cytopenias while on treatment. In such patients, the
      close monitoring of blood counts is necessary. Larger studies are needed to
      confirm these findings and to determine whether SVR differs in this population.

PMID- 17001401
TI  - The utility of serum receptor-binding cancer antigen expressed on SiSo cells in
      gastrointestinal tract cancers.
AB  - BACKGROUND: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a
      novel tumour marker that has been described in various kinds of cancer. The
      majority of observations include immunohistochemical studies; however, there are
      not enough data about the utility of this antigen as a serum tumour marker and
      its tumour specificity. AIM: To measure the serum levels of RCAS1 in patients
      with gastrointestinal (GI) tract cancers and compare them with other GI tract
      tumour markers. PATIENTS AND METHODS: Sera collected from patients with GI
      cancers (14 esophagus, 32 gastric and 36 colon) and from healthy volunteers (30
      individuals) were analyzed for RCAS1 and compared with carcinoembryonic antigen
      (CEA) and cancer antigen 19-9. The relationship between serum RCAS1, tumour stage
      and tumour grade was also evaluated. RESULTS: Mean serum RCAS1 level was higher
      in patients with GI tract cancers compared with the control group (P=0.001).
      Among GI tract cancers, RCAS1 had lowest and highest sensitivity for esophagus
      and colon cancer diagnosis, respectively. Serum RCAS1 had a higher sensitivity
      for malignancy, except in the colon, and lower specificity in all groups compared
      with CEA. In comparison with cancer antigen 19-9, serum RCAS1 was more sensitive
      but less specific for all GI cancer groups. Mean serum RCAS1 levels were not
      statistically significant among histopathological tumour types (P>0.05). Although
      serum RCAS1 levels were significantly higher in cases with lymph node involvement
      compared with lymph node-negative cases (P=0.009), there was no difference
      between cases with and without serosal involvement, vascular invasion and distant
      metastasis; no correlation was found between tumour size and RCAS1 levels.
      CONCLUSIONS: RCAS1 may be used and combined with CEA as a tumour marker in GI
      tract cancers.

PMID- 17001402
TI  - The effect of information level and coping style on pain and anxiety in needle
      liver biopsy.
AB  - Biopsy of the liver is an important diagnostic procedure. The procedure is
      invasive and may be painful for patients. Sedative drugs are not used because the
      associated drop in blood pressure mimics hemorrhage, a major complication of the
      procedure. Cognitive and behavioural techniques have been used to decrease stress
      in patients undergoing other medical procedures. In the present study, it is
      postulated that providing procedural and sensory information may reduce patient
      anxiety levels. Patient coping styles were evaluated and anxiety and pain levels
      were assessed by using a visual analogue scale. Subjects were randomly assigned
      to one of two groups. The control group received basic information about the
      procedure. The experimental group received the same basic information followed by
      more detailed educational information. Subjects also filled out the Krantz Health
      Opinion Survey, a short questionnaire used to classify coping styles as either
      information-seeking or information-avoiding. Seventy-five subjects (38 control
      and 37 experimental) with similar demographics were included in the present
      study. No significant differences were found in anxiety levels or pain levels 30
      min and 6 h post-biopsy. There was also no significant difference between groups
      once coping style was added into the analysis. The study failed to show any
      advantage in providing additional information to subjects before liver biopsy,
      regardless of coping style.

PMID- 17001404
TI  - Unravelling single metalloprotein electron transfer by scanning probe techniques.
AB  - This review is intended to account for the experimental and theoretical
      achievements obtained in a period of about 15 years on the investigation of the
      electron transport through single redox metalloproteins by scanning probe
      techniques. A highly focussed research effort has been deployed by the scientists
      active in this particular field towards measuring and interpreting electronic
      current signals flowing via blue copper, redox metalloproteins (e.g. azurin). The
      field has taken a remarkable advantage of the use of electrochemically assisted
      scanning tunnelling microscope (EC-STM) which has allowed to probe single
      molecule signals under full control of all the potential values involved in the
      experiments. This experimental activity has both triggered more comprehensive
      theoretical interpretations and has been, in its turn, stimulated by
      theoreticians to test always new predictions. The authors hope to have succeeded
      in providing the reader with a valuable appraisal of this fascinating field.

PMID- 17001405
TI  - Towards chemical accuracy for the thermodynamics of large molecules: new hybrid
      density functionals including non-local correlation effects.
AB  - Two hybrid density functionals that include a second-order perturbation
      correction for non-local correlation effects are tested for the full G3/05 test
      set. Very large AO basis sets including core-polarization/correlation functions
      have been employed that yield for the first time results quite close to the basis
      set limit for this set. The B2-PLYP functional and the new mPW2-PLYP approach
      with a modified exchange part give by far the lowest MAD over the whole G3/05 set
      ever reported for a DFT method (2.5 and 2.1 kcal mol(-1), respectively). The big
      improvement compared to common density functionals is further demonstrated by the
      reduction of the maximum and minimum errors (outliers) and by much smaller errors
      for complicated molecular systems.

PMID- 17001406
TI  - Induced hyper-valence of carbon in metal:fluorocarbon complexes.
AB  - Charge-transfer in combination with geometric features induces a pentavalent
      state of the carbon atom in metastable super-fluorinated alkali-metal compounds,
      M:C2F7 (M = K to Cs).

PMID- 17001407
TI  - Studying electron transfer through alkanethiol self-assembled monolayers on a
      hanging mercury drop electrode using potentiometric measurements.
AB  - A new approach based on measuring the change of the open-circuit potential (OCP)
      of a hanging mercury drop electrode (HMDE), modified with alkanethiols of
      different chain length conducted in a solution containing a mixture of
      Ru(NH3)6(2+) and Ru(NH3)6(3+) is used for studying electron transfer across the
      monolayer. Following the time dependence of the OCP allowed the extraction of the
      kinetic parameters, such as the charge transfer resistance (R(ct)) and the
      electron transfer rate constant (k(et)), for different alkanethiol monolayers. An
      electron tunneling coefficient, beta, of 0.9 A(-1) was calculated for the
      monolayers on Hg.

PMID- 17001408
TI  - Molecular dynamics simulations of peptide carboxylate hydration.
AB  - Aqueous solvation of carboxylate groups, as present in the glycine zwitterion and
      the dipeptide aspartylalanine, is studied employing a force-field that includes
      distributed multipole electrostatics and induction contributions (Amoebapro: P.
      Ren and J. W. Ponder, J. Comput. Chem., 2002, 23, 1497; P. Ren and J. W. Ponder,
      J. Phys. Chem. B, 2003, 107, 5933; J. W. Ponder and D. A. Case, Adv. Protein
      Chem., 2003, 66, 27). Radial and orientation distribution functions, as well as
      hydration numbers, are calculated and compared with existing simulation data
      derived from Car-Parrinello molecular dynamics (CPMD), and also distributed
      charge force-fields. Connections are also made with experimental data for
      solvation of carboxylates in water. Our findings show that Amoebapro yields
      carboxylate solvation properties in very good agreement with CPMD results,
      significantly closer agreement than can be obtained from traditional force
      fields. We also demonstrate that the influence of solvation on the conformation
      of the dipeptide is markedly different using Amoebapro compared with the other
      force-fields.

PMID- 17001409
TI  - An ab initio investigation of the O(3P)-H2(1sigma(g)+) van der Waals well.
AB  - We report an ab initio study of the van der Waals region of the O(3P)-H2
      potential energy surface based on RCCSD(T) calculations with an aug-cc-pVQZ basis
      supplemented by bond functions. In addition, an open-shell implementation of
      symmetry-adapted perturbation theory (SAPT) is used to corroborate the RCCSD(T)
      calculations and to investigate the relative magnitudes of the various
      contributions to the van der Waals interaction. We also investigate the effect of
      the spin-orbit coupling on the position and depth of the van der Waals well. We
      predict the van der Waals minimum to occur in perpendicular geometry, and located
      at a closer distance than a secondary well in colinear geometry. The potentials
      obtained in the present study confirm the previous calculations of Alexander [M.
      H. Alexander, J. Chem. Phys., 1998, 108, 4467], but disagree with the earlier
      work of Harding and co-workers [Z. Li, V. A. Apkarian and L. B. Harding, J. Chem.
      Phys., 1997, 106, 942] as well as with recently refitted surfaces of Brandao and
      coworkers [J. Brandao, C. Mogo and B. C. Silva, J. Chem. Phys., 2004, 121, 8861].
      Inclusion of spin-orbit coupling reduces the depth of the van der Waals minimum
      without causing a change in its position.

PMID- 17001410
TI  - Theoretical study on stabilities of multiple hydrogen bonded dimers.
AB  - A series of self-constituted multiple hydrogen bonded (MHB) complexes has been
      investigated systematically by density functional theory (PBE1PBE /6-31G**), the
      Morokuma energy decomposition method (HF/6-31G**) and MP2 (6-31G** and 6
      311++G**) calculation. We have discovered that (i) for doubly hydrogen bonded
      (DHB) complexes, both the interaction energy and stability increase with the
      charge transfer energy; (ii) for quadruple hydrogen bonded (QHB) complexes,
      cooperativity is the most important factor determining stability of the complex:
      stronger cooperative energy correlates well with larger interaction energy and
      thus more stable complex and vice versa; (iii) correlation energy plays an
      important role in intermolecular interactions. The correlation energy, mainly
      consisting of dispersive energy, also exhibits cooperativity in MHB dimers:
      positive for M-aadd and generally negative for other complexes.

PMID- 17001411
TI  - Ammonium ions in alkali metal halide crystals: tunnelling and spin relaxation.
AB  - We have used low energy inelastic neutron scattering spectroscopy to examine the
      tunnelling spectroscopy of the ammonium ion in the (NH4)0.02Rb(x)K(0.98-x)I
      system. The concentration of different species were varied as x increased, this
      was followed systematically and the first consistent assignment scheme for these
      features is given. Differences were also found for the relaxation rate of the
      spin temperature inversions that could be generated in these species. At a
      critical concentration--about x = 0.04 mole fraction--the relaxation rates of the
      species changed dramatically.

PMID- 17001412
TI  - Mass-analyzed threshold ionization spectroscopy of pyridine. Structural
      distortion in the first excited state.
AB  - For the first time, vibrational spectra of the pyridine cation in the electronic
      ground state have been measured via several intermediate states (0(0), 16b0(2),
      16b0(4), 6a0(1), 6b(1), 16a0(1), 10a0(1) and 12(1)) by Mass-Analyzed Threshold
      Ionization (MATI) spectroscopy. From the MATI spectra, the adiabatic ionization
      energy of pyridine has been determined to be 74,185 +/- 6 cm(-1) (9.1978 +/-
      0.0008 eV). Several vibronic modes in the ionic ground state could be assigned
      for the first time. An intensity gain of vibrations having b1 symmetry could be
      observed by activating the ion ground state. Also, a breakdown of the "delta nu =
      0 propensity rule" for the excitation via the 16b(2) and 16b(4) states of the
      first excited states are displayed in the recorded spectra. In conjunction with
      ab initio calculations these observations can be explained by a strong
      geometrical distortion along the 16b vibration in the first excited state,
      leading to a "boat distortion".

PMID- 17001413
TI  - Intra- vs. intermolecular hydrogen bonding: dimers of alpha-hydroxyesters with
      methanol.
AB  - Intermolecular hydrogen bonding competes with an intramolecular hydrogen bond
      when methanol binds to an alpha-hydroxyester. Disruption of the intramolecular
      OH...O=C contact in favour of a cooperative OH...OH...O=C sequence is evidenced
      by FTIR spectroscopy for the addition of methanol to the esters methyl glycolate,
      methyl lactate and methyl alpha-hydroxyisobutyrate in seeded supersonic jet
      expansions. Comparison of the OH stretching modes with quantum-chemical harmonic
      frequency calculations and 18O labelling of methanol unambiguously prove the
      insertion of methanol into the intramolecular hydrogen bond. This is in marked
      contrast to UV/IR hole burning studies of the homologous system methyl lactate:
      (+/-)-2-naphthyl-1-ethanol, where only addition complexes were found and the
      intramolecular hydrogen bond was conserved. This switch in hydrogen bond pattern
      from aliphatic to aromatic heterodimers is thought to reflect not only a kinetic
      propensity but also a thermodynamic preference for addition complexes when
      dispersion forces become more important in aromatic systems.

PMID- 17001414
TI  - Adsorption of polycyclic aromatic hydrocarbons at the air-water interface:
      molecular dynamics simulations and experimental atmospheric observations.
AB  - Adsorption of benzene, naphthalene, anthracene, and phenanthrene at the aqueous
      surface is investigated by means of molecular dynamics simulations. Potentials of
      mean force, i.e., free energy profiles obtained when moving the studied molecules
      across an aqueous slab were evaluated. In all cases, deep surface free energy
      minima, corresponding to orders of magnitude of surface enhancement of the
      aromatic molecule, were located. This enhancement, which increases with the size
      of the solute, points to the importance of the aqueous surface for the chemistry
      of polycyclic aromatic hydrocarbons (PAHs). Supporting evidence in the
      atmospheric environment related to the heterogeneous chemistry of PAHs on water
      droplets and planar surfaces is summarized. There is good agreement between the
      hydration free energies computed from MD calculations and the experimentally
      determined values. Data pertaining to the importance of the air-water interface
      in the adsorption and transport of PAHs on micron sized water droplets are
      described. The relevant data on adsorption and reaction (ozonation and
      photochemical) at the air-water interface of planar surfaces and droplets are
      also summarized.

PMID- 17001415
TI  - The uptake of O3 by myristic acid-oleic acid mixed particles: evidence for solid
      surface layers.
AB  - The oleic acid ozonolysis in mixed oleic and myristic acid particles was studied
      in a flow tube reactor using single particle mass spectrometry. The change in
      reactivity was investigated as a function of the myristic acid concentration in
      these 2 micron particles. For pure oleic acid aerosol, the reactive ozone uptake
      coefficient, gamma, was found to be 3.4 (+/-0.3) x 10(-4) after taking secondary
      reactions into account. At the myristic acid crystallization point, where only
      2.5% of the particle is in the solid phase, the uptake coefficient was reduced to
      9.7 (+/-1.0) x 10(-5). This dramatic drop in the uptake coefficient is explained
      by the presence of a crystalline monolayer of myristic acid, through which ozone
      diffusion is reduced by several orders of magnitude, relative to liquid oleic
      acid. Scanning electron microscope images of the mixed particles confirm that the
      particle surface is crystalline when the myristic acid mole fraction exceeds
      0.125. The findings of these experiments illustrate that particle morphology is
      important to understanding the reactivity of species in a mixed particle. The
      decay of myristic acid during the course of ozonolysis is explained in terms of a
      reaction with stabilized Criegee intermediates, which attack the acidic groups of
      the oleic and myristic acids with equal rate constants.

PMID- 17001416
TI  - Impedance spectroscopy of reduced monoclinic zirconia.
AB  - Zirconia doped with low-valent cations (e.g. Y3+ or Ca2+) exhibits an
      exceptionally high ionic conductivity, making them ideal candidates for various
      electrochemical applications including solid oxide fuel cells (SOFC) and oxygen
      sensors. It is nevertheless important to study the undoped, monoclinic ZrO2 as a
      model system to construct a comprehensive picture of the electrical behaviour. In
      pure zirconia a residual number of anion vacancies remains because of
      contaminants in the material as well as the thermodynamic disorder equilibrium,
      but electronic conduction may also contribute to the observed conductivity.
      Reduction of zirconia in hydrogen leads to the adsorption of hydrogen and to the
      formation of oxygen vacancies, with their concentration affected by various
      parameters (e.g. reduction temperature and time, surface area, and water vapour
      pressure). However, there is still little known about the reactivities of defect
      species and their effect on the ionic and electronic conduction. Thus, we applied
      electrochemical impedance spectroscopy to investigate the electric performance of
      pure monoclinic zirconia with different surface areas in both oxidizing and
      reducing atmospheres. A novel equivalent circuit model including parallel ionic
      and electronic conduction has previously been developed for titania and is used
      herein to decouple the conduction processes. The concentration of defects and
      their formation energies were measured using volumetric oxygen titration and
      temperature programmed oxidation/desorption.

PMID- 17001417
TI  - Controlling rheumatic heart disease in developing countries.

PMID- 17001418
TI  - Some in vitro and in vivo cardiovascular effects of Hypoxis hemerocallidea Fisch
      & CA Mey (Hypoxidaceae) corm (African potato) aqueous extract in experimental
      animal models.
AB  - This study was undertaken to investigate some cardiovascular effects of Hypoxis
      hemerocallidea Fisch & CA Mey (Hypoxidaceae) corm (African potato) aqueous
      extract in experimental animal paradigms. The effect of the corm aqueous extract
      (APE) on myocardial contractile performance was evaluated on guinea-pig isolated
      atrial muscle strips in vitro; whereas the antihypertensive (hypotensive) effect
      of the plant extract was examined in hypertensive Dahl salt-sensitive rats in
      vivo. APE (25-400 mg/ml) produced concentration-dependent, significant (p < 0.05
      0.001) negative inotropic and negative chronotropic effects on guinea-pig
      isolated electrically driven left, and spontaneously beating right atrial muscle
      preparations, respectively. Moreover, APE reduced or abolished, in a
      concentrationdependent manner, the positive inotropic and chronotropic responses
      of guinea-pig isolated atrial muscle strips induced by noradrenaline (NA, 1-100
      microM) and calcium (Ca2+, 5-40 mM). The negative inotropic and chronotropic
      effects of APE on guinea-pig atrial muscle strips were not modified by exogenous
      administration of atropine (ATR, 7.5 x 10(-7)-2.5 - 10(-6) M) to the bath fluid.
      APE also significantly reduced (p < 0.05-0.001) or abolished in a concentration
      dependent manner, the rhythmic, spontaneous, myogenic contractions of portal
      veins isolated from rats. Furthermore, APE caused dose-related transient but
      significant (p < 0.05-0.001) reductions in the systemic arterial blood pressure
      and heart rates of the hypertensive rats used. Although the exact mechanisms of
      the cardiodepressant and the transient hypotensive (antihypertensive) actions of
      APE could not be established in the present study, we exclude the involvement of
      the cholinergic system; since the extract's cardiovascular effects were resistant
      to atropine pretreatment. However, the results of this laboratory animal study
      indicated that APE caused bradycardia and brief hypotension in the mammalian
      experimental models used. These observations tend to suggest that the herb may be
      used as a natural supplementary remedy in some cases of cardiac dysfunctions and
      in essential hypertension. The findings of this experimental animal study lend
      pharmacological support to the folkloric, anecdotal uses of the African potato in
      the management and/or control of certain cardiac dysfunctions and essential
      hypertension in some rural communities of southern Africa.

PMID- 17001419
TI  - A model for determining baseline morphometrics of the capillary bed in skeletal
      muscle.
AB  - Changes in capillary diameter (CD) have been used to detect the effect of
      pharmacological interventions, physical treatments and ischaemic reperfusion
      injury in skin and muscle. For comparison, CDs within similar structures in the
      untreated limb of the same subject have been used as the control, with the
      assumption that CDs are the same in both limbs. This study employs light
      microscopic morphometry (LMM) to explore this premise, investigates the
      repeatability of LMM and determines the number of CDs that should be measured to
      produce a reliable result. Muscle biopsies were obtained from the left (L) and
      right (R) vastus lateralis of four rabbits and the left and right tibialis
      anterior of three vervet monkeys. Thin (1-micro m) resin sections were prepared
      for LMM examination and CDs were measured using computerised image analysis. To
      determine the repeatability of measurement, two specimens were re-measured on
      five occasions at monthly intervals. The mean CD of each biopsy from L and R
      limbs were compared and the number of measurements necessary to produce a result
      with less than a 3% difference was determined. A minimum of 58 and a maximum of
      175 CDs were measured from each specimen. Repeated measurement of the same
      biopsies showed a non-significant mean difference of less than 2% in CD means
      between the first measurement and each of the four subsequent measurements. There
      was a non-significant difference of 3.7% in CD means between R and L limbs in one
      animal, in which less than 70 CDs were measured on each side. When 100 CDs or
      more were measured, the difference was always less than 2.3%. When grouped, the
      difference in CD means between L and R limbs was 0.5% in rabbits and 2.0% in
      vervet monkeys. The results confirm that firstly, CD data derived from a muscle
      in an untreated limb can be used as a control for experiment-mediated changes of
      CD in the other; secondly, LMM appears to be a reliable means of measuring CD;
      and thirdly, while fewer measurements may suffice, ideally 75-100 CDs are needed
      to provide a dependable result.

PMID- 17001420
TI  - An experience with cardiopulmonary bypass in HIV-infected patients.
AB  - Having noted the good clinical status of some HIV patients who were referred for
      but refused surgery, we undertook surgery with the aim of determining outcome,
      risk-to-benefit ratio and, if possible, the effect of surgery with
      cardiopulmonary bypass (CPB) on the progression of their HIV disease.
      Antiretroviral drugs (ARVD) were not available to these patients. The records of
      49 patients, 17 males and 32 females, aged between 17 and 67 years, undergoing
      surgery with cardiopulmonary bypass over a nine-year period, were reviewed. Forty
      eight of these underwent cardiac surgery and one aortic dissection repair. Four
      HIV-infected patients underwent surgery with good early outcome. Thereafter an
      absolute CD4 cell count greater than 400/microl (normal 550*1 955/microl) and the
      absence of the stigmata of AIDS in patients fulfilling the normal criteria for
      surgery allowed cardiac surgery using CPB. Fifty operations were performed. Three
      patients with CD4 counts of 37, 868 and 1 245/microl died early, giving a 30-day
      mortality of 6% for 50 procedures. Six patients with active infective
      endocarditis (IE) underwent emergency surgery. Three of these, one with a pre-
      and two with only post-operative counts all below 250/microl, died within three
      months. Sixteen complications occurred in the remaining 46 patients (34.7%). Pre
      operative CD4 cell counts taken in 42 patients averaged 685/microl. Pre- and post
      operative counts known in eight showed variations, as did repeated counts in
      those awaiting surgery. Forty-one patients left hospital in the New York Heart
      Association (NYHA) class I, five in class II and one in class III. Prior to
      surgery, the majority (38) were in class III and seven were in class IV. Follow
      up ranging from two to 70 months averaged 23.1 months. Eight late deaths
      occurred, three related to AIDS. We found surgery to be worthwhile in selected
      HIV-infected patients. Early outcome paralleled that in the uninfected, giving a
      low risk-to-benefit ratio. Emergency surgery in those with active infective
      endocarditis and marked immune compromise met with high mortality. It is
      essential in our population to test and stage all patients for HIV. We could not
      show that CPB accelerated progression to AIDS. This experience and the present
      availability of ARVDs would enable us to review our selection criteria for
      surgery.

PMID- 17001421
TI  - Salt intake in an urban, developing South African community.
AB  - INTRODUCTION: Present guidelines for the diagnosis and management of hypertension
      indicate that a reduction in sodium (Na(+)) intake levels and an increase in
      potassium (K(+)) intake levels are critical components of blood pressure (BP)
      control. Whether this is being successfully implemented in urban, developing
      communities in South Africa is uncertain. AIMS: The first was to assess how mean
      24-hour urinary Na(+) and K(+) excretion rates, used as an index of salt intake,
      compared against recommended daily allowances (RDA) for Na(+) and K(+) intake in
      an urban, developing South African community. The second was to determine the
      relationship between hypertension awareness and treatment, and 24- hour urinary
      Na(+) and K(+)excretion rates in this community. METHODS: Four hundred and thirty
      eight subjects living in metropolitan areas of Johannesburg, of whom 291 had
      complete 24-hour urine collections and BP measurements, obtained on three
      separate occasions, were randomly recruited. Thirty-one per cent of the sample of
      291 subjects were hypertensive (either receiving therapy or with an average BP
      measured on three separate occasions > or =140/90 mmHg). Sixty-seven per cent of
      hypertensives were aware of their hypertension and were being treated for it. On
      average, 82% of subjects had 24-hour Na+ excretion values above the RDA for Na(+)
      intake of 65 mmol/day. All subjects had 24- hour K(+) excretion rates below the
      RDA for K(+) intake (120 mmol/day). The mean value for 24-hour urinary Na(+) and
      K(+) excretion rates (mmol/24 hours) in patients who were aware of their
      hypertension and receiving treatment for it (n = 61; Na(+) = 112 +/- 54, K(+) =
      32 +/- 16) was similar to that of patients who were unaware of their hypertension
      (n = 30; Na(+) = 102 +/- 49, K(+) = 28 +/- 13), or to normotensives (n = 200;
      Na(+) = 117 +/- 56, K(+) = 33 +/- 17). Hypertension awareness and treatment were
      not associated with electrolyte excretion rates either when considered alone or
      after adjusting for age, gender, body mass index, alcohol and tobacco intake, the
      presence of diabetes mellitus and the type of antihypertensive therapy
      (multivariate regression analysis). Moreover, the proportion of patients who were
      aware of their hypertension, were receiving treatment for it, and who had 24-hour
      Na(+) excretion values above the RDA for Na(+) intake (80%) was similar to the
      proportion noted in those who were unaware of their hypertension (73%), and to
      normotensives (84%). CONCLUSIONS: The lack of relationship between either
      hypertension awareness and treatment, and Na(+) and K(+) intake levels suggests
      that current recommendations for a reduced Na(+) and increased K(+) intake in
      hypertensives do not translate into clinical practice in urban, developing
      communities of South Africa.

PMID- 17001423
TI  - New simulation-technology training for interventionalists in South Africa:
      Baroque Medical and Abbott Vascular Satellite Institute.

PMID- 17001422
TI  - Blood pressure-measuring devices in rural South Africa: an audit conducted by the
      SASPI team in the Agincourt field site.
AB  - BACKGROUND: Cardiovascular disease is an important cause of morbidity and
      mortality in South Africa. The Southern Africa Stroke Prevention Initiative
      (SASPI) found a high prevalence of stroke in the rural Agincourt subdistrict,
      Limpopo province. Hypertension is the commonest vascular risk factor in our
      population and it is essential that primary care services be adequately equipped
      to detect and treat hypertension. The aim of this study was to assess the number,
      accuracy and working condition of blood pressure measuring devices (BMD) in the
      clinics that serve the field site, and to assess the clinic sisters' perceptions
      of the availability of antihypertensive medication and aspirin. METHODS: In each
      of the clinics serving the site we assessed the BMDs and cuffs using the
      following criteria: general condition, bladder size, state of rubber components,
      operation of the inlet valve and control of valve operation. The legibility of
      the gauge, level and condition of the mercury, and the condition of the glass
      tube were checked when relevant. The performance of the BMD was then assessed
      both with the cuff used in the clinic and with a new functioning cuff, against an
      accurate mercury sphygmomanometer. By interviewing the clinic sister we could
      assess the availability of antihypertensive medication and aspirin, as well as
      the state of the drug delivery system. RESULTS: All BMDs were mercury
      sphygmomanometers. Four clinics had one BMD each, one clinic had two, and one
      clinic had four. In one clinic the device was not functional at all until the
      study cuff was used. None of the clinics had spare cuffs and only one clinic had
      access to a large cuff. Nine out of 10 (90%) cuffs tested had unsatisfactory
      valve function, and none was of the size recommended by the guidelines. Although
      the condition of the mercury was only considered satisfactory in 40% of BMDs,
      once a new cuff had been fitted to the BMDs all of them were accurate to within 4
      mmHg between 50 and 250 mmHg. Fifty per cent of clinic sisters felt they always
      had sufficient stock of hydrochlorothiazide and alpha-methyldopa, but the supply
      of more expensive medication was less reliable. Only one clinic always had
      sufficient aspirin. CONCLUSION: Although none of the primary care clinics had
      fully functioning BMDs, almost all the defects related to malfunctioning and
      inappropriately sized cuffs, which would be inexpensive to repair or replace. A
      procedure for routine servicing or replacement of both BMDs and cuffs is needed,
      as well as optimisation of medication delivery to remote areas.

PMID- 17001424
TI  - Late complication after closure of a ventricular septal rupture.

PMID- 17001425
TI  - Improving endothelial function and reducing remodeling post-MI are key to
      perindopril benefits in coronary artery disease.

PMID- 17001426
TI  - High-dose atorvastatin therapy achieves 25% reduction in CV events in TNT
      substudy of diabetic patients.

PMID- 17001427
TI  - Moxonidine well tolerated and effective in the treatment of viscerally obese, non
      controlled hypertensive patients.

PMID- 17001428
TI  - Telmisartan provides superior BP reduction from morning to morning compared to
      other leading ARBs.

PMID- 17001429
TI  - Acute coronary syndromes: clearing up controversies in clopidogrel use.

PMID- 17001430
TI  - Abdominal obesity and cardiovascular risk: does waist circumference tell the
      story?

PMID- 17001431
TI  - Simvastatin effectively reduced all triglyceride-rich liporoteins (VLDL and LDL)
      in type 2 diabetes using VAP analysis.

PMID- 17001432
TI  - SA Hypertension Guidelines set minimum standards for medical aid schemes.

PMID- 17001433
TI  - Tight glycaemic control using soluble insulin benefits critically ill patients
      during hospitalisation.

PMID- 17001434
TI  - Synagis now registered for the prevention of RSV disease in children with CHD.

PMID- 17001435
TI  - Pfizer launches Inspra for heart failure.

PMID- 17001436
TI  - Reliability, validity and responsiveness of the German Short Musculoskeletal
      Function Assessment Questionnaire in patients undergoing surgical or conservative
      inpatient treatment.
AB  - OBJECTIVE: The patient-based evaluation of outcome is gaining increased
      importance. The aim of the study was to demonstrate the reliability, validity and
      responsiveness of the German version of the Short Musculoskeletal Function
      Assessment Questionnaire (SMFA-D) in patients undergoing surgical or conservative
      treatment. METHODS: Three hundred and thirty-two patients suffering from
      osteoarthritis of the hip or knee, rheumatoid arthritis or rotator cuff tear
      undergoing surgical or medical inpatient treatment were followed up for 12 month.
      Patients underwent both SMFA-D and other assessments and clinical as well as
      radiological examinations. Reliability, validity and responsiveness of the SMFA-D
      were evaluated. RESULTS: Values of the SMFA-D subscales, Function index (M 22-49,
      SD 12-20, range 0-96) and Bother index (M 29-52, SD 15-23, range 0-100), showed a
      normal distribution. Internal consistency (0.88-0.97) and retest reliability
      (0.71-0.96) coefficients were satisfactory to excellent. In most cases, the SMFA
      D correlated significantly with function tests, physicians' function ratings,
      patients' pain ratings and other quality-of-life questionnaires in all patient
      subgroups. The results support both the construct and criterion validity of the
      measure. Different patient groups and subgroups could be discriminated with the
      SMFA-D scales. The standardized response means of SMFA-D subscales were in
      surgical patients better than in conservatively treated patients and comparable
      to those of the SF-36 Physical Component Summary scale. CONCLUSIONS: The German
      version of SMFA is a reliable, valid and responsive questionnaire in patients
      with osteoarthritis of the hip or knee, rheumatoid arthritis or rotator cuff tear
      undergoing surgical or medical inpatient treatment. Thus, the use of the SMFA-D
      in these patients can be recommended.

PMID- 17001437
TI  - A patient-based questionnaire to assess outcomes of foot surgery: validation in
      the context of surgery for hallux valgus.
AB  - BACKGROUND: A patient-based outcome measure with good measurement properties is
      urgently needed for use in clinical trials of foot surgery. METHODS: We evaluated
      an existing foot pain and disability questionnaire (the Manchester Foot Pain and
      Disability Questionnaire) for its suitability as an outcome measure in the
      context of hallux valgus corrective surgery. Interviews with patients led to
      initial changes, resulting in 20 candidate questionnaire items with five response
      categories each. These were tested in a prospective study of 100 patients
      (representing 138 foot operations) undergoing hallux valgus corrective surgery.
      Analysis of underlying factor structure, dimensionality, internal reliability,
      construct validity and responsiveness of the questionnaire items in relation to
      (i) SF-36 general health survey and (ii) American Orthopaedic Foot & Ankle
      Society (AOFAS) hallux clinical scale resulted in a final 16 item questionnaire
      (the 'Manchester-Oxford Foot Questionnaire' (MOXFQ)), consisting of three
      domains/scales: 'Walking/standing' (seven items), 'Pain' (five items) and 'Social
      interaction' (four items) each having good measurement properties. All three
      domains were unidimensional. CONCLUSIONS: The new 16-item MOXFQ has good
      measurement properties in the context of outcomes assessment of surgery for
      hallux valgus. Future studies should assess the MOXFQ in the context of surgery
      for other foot and ankle conditions.

PMID- 17001438
TI  - Factor analysis techniques for assessing sufficient unidimensionality of cancer
      related fatigue.
AB  - BACKGROUND: Fatigue is the most common unrelieved symptom experienced by people
      with cancer. The purpose of this study was to examine whether cancer-related
      fatigue (CRF) can be summarized using a single score, that is, whether CRF is
      sufficiently unidimensional for measurement approaches that require or assume
      unidimensionality. We evaluated this question using factor analysis techniques
      including the theory-driven bi-factor model. METHODS: Five hundred and fifty five
      cancer patients from the Chicago metropolitan area completed a 72-item fatigue
      item bank, covering a range of fatigue-related concerns including intensity,
      frequency and interference with physical, mental, and social activities.
      Dimensionality was assessed using exploratory and confirmatory factor analysis
      (CFA) techniques. RESULTS: Exploratory factor analysis (EFA) techniques
      identified from 1 to 17 factors. The bi-factor model suggested that CRF was
      sufficiently unidimensional. CONCLUSIONS: CRF can be considered sufficiently
      unidimensional for applications that require unidimensionality. One such
      application, item response theory (IRT), will facilitate the development of short
      form and computer-adaptive testing. This may further enable practical and
      accurate clinical assessment of CRF.

PMID- 17001440
TI  - Defining pelvic factors in sphincter-preservation of low rectal cancer with a
      three-dimensional digital model of pelvis.
AB  - PURPOSE: Surgeons often can contribute failure of sphincter-preserving procedure
      to a limitation of pelvis anatomy; however, they cannot determine definitely
      which anatomic diameter or spatial factor actually affected the success of the
      procedure. METHODS: Colorectal surgeons, radiologists, and research fellows
      collaborated closely to establish a three-dimensional digital model of the pelvis
      with spiral computerized tomography scanning data of patients with rectal cancer.
      Retrospective analysis on data of 97 patients with low rectal cancer was
      performed with this model to identify geometric factors that might affect a
      successful sphincter preservation procedure for low rectal cancer. RESULTS: A
      digital pelvic model was established. Multivariate analysis demonstrated that
      distance from the anal verge, body mass index, and pelvic factors affected the
      success of sphincter preservation. Sphincter preservation was more likely to
      succeed when the distance from anal verge was > or =5 cm and body mass index was
      <25 kg/m(2). Shorter diameter from the upper pubis to the sacrococcyx, distance
      of sacrococcyx, and excessive curvature of the sacrum predicted failure of
      sphincter preservation in certain cases. CONCLUSIONS: Pelvic diameters could
      affect the success of sphincter preservation for low rectal cancer patients
      besides the distance from anal verge and body mass index.

PMID- 17001441
TI  - Day-case laparoscopic cholecystectomy: treatment of choice for selected patients?
AB  - BACKGROUND: The authors report their 7-year experience with day-case laparoscopic
      cholecystectomy (LC) to determine its applicability, safety, and cost
      effectiveness. METHODS: Of 920 consecutive patients who underwent elective LC
      over a 7-year period, 567 (62%) were scheduled for day-case surgery. The median
      age of the patients was 48 years (range, 16-74 years), and the male/female ratio
      was 148/419. The selection criteria required an American Society of
      Anesthesiologists (ASA) grade of 1 or 2, absence of morbid obesity, low risk of
      common bile duct stones, adult company at home, and residence within 100 km of
      the hospital. The LC procedure was performed using a standard four-cannula
      technique. Propofol-opiate-rocuron-sevoflurane anesthesia, prophylactic
      antiemetics, and preemptive analgesia were administered in all cases. RESULTS:
      The mean length of the operation was 56 +/- 18 min. There was no hospital
      mortality, and 7 (1.2%) of 567 patients required conversion to open
      cholecystectomy. Approximately 356 (63%) of the 567 patients were discharged home
      on the same day as the operation, whereas 211 patients (37%) were admitted
      overnight after the operation because of social reasons (13.7%), surgeon
      preference (15.2%), nausea and/or pain (15.2%), operation late in the afternoon
      (14.2%), or patient preference (41.7%). There were no serious complications. A
      total of 22 patients visited the emergency unit, and 7 patients required
      readmission, giving a readmission rate of 2%. The overall postoperative morbidity
      rate was 6% (n = 22), with morbidities including retained stones (n = 2), bile
      leakage (n = 1), and pneumonia (n = 1). The mean procedural cost to the hospital
      was 1,836 euros for day-case LC, as compared with 2,712 euros for an inpatient
      operation. CONCLUSIONS: For selected patients, day-case LC is feasible and safe,
      providing a substantial reduction in hospital costs.

PMID- 17001442
TI  - Strength of tissue attachment to mesh after ventral hernia repair with synthetic
      composite mesh in a porcine model.
AB  - BACKGROUND: A prospective animal study involving 12 female swine aimed to measure
      the strength of tissue attachment to composite mesh at various time points after
      laparoscopic ventral hernia repair in a porcine model. METHODS: Each animal had
      two 10 x 16-cm sheets of polypropylene/expanded polytetrafluoroethylene (ePTFE)
      composite mesh laparoscopically affixed to the abdominal wall with a helical
      tacking device. No transfascial sutures were used. The animals were euthanized 2,
      4, 6, and 12 weeks after surgery, and abdominal walls were resected en bloc with
      the patches. Each patch was cut into 2 x 7-cm strips, and each strip was
      independently analyzed. The strength of the tissue attachment to the mesh was
      measured using a servohydraulic tensile testing frame. The abdominal wall was
      peeled from the mesh, and the transverse, or "lap-shear" force was recorded. Data
      are reported as mean force in pounds. RESULTS: The mean lap-shear force was 0.83
      +/- 0.06 lbs at 2 weeks, 1.06 +/- 0.07 lbs at 4 weeks, 0.88 +/- 0.08 lbs at 6
      weeks, and 1.13 +/- 0.07 lbs at 12 weeks. The mean force was higher at 12 weeks
      than at 2 weeks (p < 0.05). No other periods were significantly different from
      any other. CONCLUSIONS: The findings demonstrate that the majority of tissue
      ingrowth and strength has occurred by 2 weeks after laparoscopic placement of a
      composite hernia prosthesis. Strength very gradually increases until 12 weeks
      after surgery. This has clinical implications for human ventral hernia repair.
      Further study is needed to evaluate the necessity of transfascial sutures for
      securing polypropylene-based prostheses to the abdominal wall during ventral
      hernia repair.

PMID- 17001443
TI  - Totally laparoscopic management of choledochal cysts using a four-hole method.
AB  - BACKGROUND: Choledochal cyst is a rare benign disease of the biliary tract.
      However, once diagnosed, it must be excised with the gallbladder because of the
      risk for cancer developing in the biliary tree, including the gallbladder. This
      report introduces a new surgical technique for totally laparoscopic excision of
      choledochal cyst and hepaticojejunostomy using a four-hole method. METHODS:
      Between October 2003 and May 2005, the authors performed totally laparoscopic
      choledochal cyst excision for 12 patients. All the patients except one were
      women, and the mean age was 37.3 years (range, 17-62 years). According to the
      Todani classification, there were five type Ia cases, four type Ic cases, and
      three type IV cases. Choledochal cyst excision and Roux-en-Y hepaticojejunostomy
      were performed laparoscopically using the four-port technique. RESULTS: The mean
      operation time was 228 min (range, 150-330 min). No operative or postoperative
      transfusion was required. An oral diet was started on postoperative day 3. The
      average length of hospital stay was 5.8 days. There was no major complication
      associated with anastomosis leakage or obstruction. No patient had an adverse
      response, as determined by clinical or laboratory evaluation during a 2- to 19
      month follow-up period. CONCLUSIONS: Considering that choledochal cyst is common
      among young women, who are especially interested in cosmetic results in addition
      to complete resolution of medical problems, the laparoscopic management of
      choledochal cyst may be an attractive treatment option.

PMID- 17001444
TI  - Anatomic landmarks: their usefulness in safe laparoscopic cholecystectomy.
AB  - The incidence of bile duct injury in laparoscopic cholecystectomy is 0.3% to
      1.0%. This is higher than the incidence reported for open cholecystectomy (i.e.,
      0.1-0.2%), and the surgeons all over the world are relentlessly trying to find
      the ways and means to lower this incidence. Various operating strategies,
      techniques, and instrumentations such as the 0 degrees telescope, intraoperative
      cholangiogram, hydrodissection, and peanut gauze dissection have been claimed by
      various authors to minimize the risk of bile duct injury during cholecystectomy.
      However, the surgical fraternity agrees that there has been no substitute for
      meticulous dissection and display of various vital structures near the common
      bile duct. The authors describe seven anatomic landmarks encountered during
      laparoscopic cholecystectomy that assist in safe dissection to prevent bile duct
      and vascular injury. On the basis of their experience, they believe that if
      surgeons adhere to these landmarks, excellent results can be achieved.

PMID- 17001445
TI  - The lasso technique for laparoscopic distal pancreatectomy.
AB  - BACKGROUND: Laparoscopic distal pancreatectomy with or without splenectomy is
      becoming an acceptable alternative to open resection for selected pancreatic
      lesions. One of the difficulties with this approach is manipulating the pancreas
      with laparoscopic instruments to avoid unnecessary injury to the pancreas, and
      yet obtain adequate margins. The described technique accomplishes these goals.
      METHODS: Data from all patients who underwent laparoscopic distal pancreatectomy
      (always with splenectomy) were reviewed for age, gender, laparoscopic completion
      of the resection, postoperative complications, length of hospital stay, and
      pathology. The essential component of the technique is use of a Penrose drain
      around the neck or proximal body of the pancreas as a "lasso" for atraumatic
      manipulation. This technique is described in detail. RESULTS: A total of 11
      patients have undergone laparoscopic distal pancreatectomy with splenectomy using
      the lasso technique. Two patients (18%) underwent conversion to an open
      laparotomy: the because of bleeding from the pancreatic parenchyma and the other
      due to local invasion of a pancreatic adenocarcinoma. The average operating time
      was 162 +/- 39 min, and the median length of hospital stay was 3 days. There were
      two (18%) pancreatic leaks, both of which were treated conservatively with
      resolution. Pathologic examination, found six cystic neoplasms, two
      neuroendocrine tumors, two masses of chronic pancreatitis, and one
      adenocarcinoma. CONCLUSIONS: The lasso technique simplifies intraoperative
      manipulation of the pancreas during laparoscopic distal pancreatectomy. It allows
      for safe manipulation of the pancreas and may expand the indications for the
      laparoscopic approach to pancreatic resection.

PMID- 17001446
TI  - Variation in proton affinity of the guanidino group between free and blocked
      arginine.
AB  - In this paper, the analog of arginine residues in peptides was synthesized and
      characterized by ESI-MS/MS (electrospray ionization with tandem mass
      spectrometry), (31)P NMR, (1)H NMR, IR and high-resolution mass spectrometry.
      When the Todd reaction activity of the guanidino group in free arginine and the
      arginine peptide analog were compared, it was found that the proton affinity of
      the guanidino group was decreased when both the N- and the C-terminal were
      blocked. As a result, the guanidino group of arginine residues in peptides could
      be phosphorylated under the Todd reaction condition, but not the free arginine.
      This result was further proved by the theoretical calculation of their proton
      affinity.

PMID- 17001447
TI  - AtGRP7 is involved in the regulation of abscisic acid and stress responses in
      Arabidopsis.
AB  - The Arabidopsis AtGRP7 gene, encoding a glycine-rich RNA-binding protein, has
      been shown to be involved in the regulation of a circadian-regulated negative
      feedback loop. However, little is known about the role of AtGRP7 in mediating
      abscisic acid (ABA) and stress responses. Here, we show that AtGRP7 plays a role
      in both. AtGRP7 was repressed by ABA, high salt and mannitol. Disruption of
      AtGRP7 by T-DNA insertion led to hypersensitive responses to ABA in both seed
      germination and root growth assays. The atgrp7-1 mutant was also hypersensitive
      to osmotic stress conditions, such as high salt and high concentrations of
      mannitol. In addition, the atgrp7-1 mutant plants accumulated significantly
      higher transcript levels of two ABA-and stress-inducible genes, RD29A and RAB18,
      compared with the wild-type plants. Taken together, these results suggest that
      AtGRP7 is involved in the regulation of ABA and stress responses.

PMID- 17001448
TI  - Osteoblast differentiation of NIH3T3 fibroblasts is associated with changes in
      the IGF-I/IGFBP expression pattern.
AB  - Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) are
      essential regulators for osteoblast proliferation and differentiation. It has
      been reported that Dexamethasone (Dex), an active glucocorticoid (GC) analogue,
      synergizes the stimulatory effect of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))
      on osteoblast differentiation in the mouse fibroblastic cell line NIH3T3. I
      investigated whether this stimulatory effect is associated with changes in the
      expression pattern of the IGF/IGFBP system. Quantitative real-time PCR technology
      was used to quantify the gene expression levels of the IGF-system during
      osteoblast differentiation and in response to 1,25(OH)(2)D(3) or Dex alone under
      serum-containing and serum-free culture conditions. Interestingly, NIH3T3 was
      shown to express high mRNA levels of IGF-I, IGF-II and IGFBP-5, and low levels of
      both IGFBP-2 and-6. During osteoblast differentiation (days 6-12), IGF-I mRNA was
      repressed by more than 60%, while the transcript of IGFBP-5 was markedly up
      regulated, by more than 50-fold. Similarly, treatment with Dex alone resulted in
      a dose-and time-dependent increase in the expression of IGFBP-5 and a decrease in
      IGF-I mRNA. Treatment with 1,25(OH)(2)D(3) alone increased the mRNA levels of IGF
      I and IGFBP-6 by around 4-and 7-fold, respectively, in a dose-and time-dependent
      manner. In conclusion, my data demonstrated that osteoblast differentiation of
      NIH3T3 is associated with changes in the expression pattern of IGFs/IGFBPs, which
      are regulated by glucocorticoid in the presence of 1,25(OH)(2)D(3). Modulation of
      the IGF/IGFBP levels by glucocorticoid might suggest important roles for the IGF
      system in mediating the osteoblast differentiation of the NIH3T3 cell line.

PMID- 17001449
TI  - Protein kinase A dependent phosphorylation activates Mg2+ efflux in the
      basolateral region of the liver.
AB  - Isolated hepatocytes in physiological [Na(+)]( 0 ) tightly maintain [Mg(2+)]( i
      ). Upon beta-adrenergic stimulation or in the presence of permeable cAMP,
      hepatocytes release 5-10% (1-3 mM Mg(2+)) of their total Mg(2+) content. However,
      isolated basolateral liver plasma membranes (bLPM), release Mg(2+) in the
      presence of [Na(+)]( o ) even in the absence of catecholamine stimulation. The
      data indicate that a physiological brake for Mg(2+) efflux is present in the
      hepatocyte and is removed upon cellular signaling. In contrast, this regulation
      "brake" is absent in purified bLPM thus rendering them fully active. The present
      study was carried out to reconstruct the missing regulatory component. Activation
      of Mg(2+) extrusion in intact cells is consistent with cAMP dependent
      phosphorylation of the transporter or a regulatory protein. Treatment of bLPM
      with a non-specific phosphatase such as alkaline phosphatase (AP), decreased
      Mg(2+) efflux by 70% compared to untreated bLPM. When AP-treated bLPM were loaded
      with protein kinase A (PKA), and stimulated with permeable cAMP, Mg(2+) transport
      fully recovered. These data suggest that phosphorylation of the Na(+)/Mg(2+)
      exchanger or a nearby protein activates the Mg(2+) transport mechanism in
      hepatocytes.

PMID- 17001450
TI  - Characterization of a novel low-molecular-mass dual specificity phosphatase-4
      (LDP-4) expressed in brain.
AB  - Dual-specificity phosphatases (DSPs), which dephosphorylate proteins at Ser/Thr
      as well as Tyr residues, are thought to be involved in critical signaling events
      such as control of MAP kinases (MAPKs). We have isolated the cDNA for a novel DSP
      and termed it low molecular mass DSP-4 (LDP-4). LDP-4 is composed of 211 amino
      acids with a predicted molecular mass of 23.9-kDa. Northern blot analysis using
      various mouse tissues showed that the LDP-4 transcript was expressed exclusively
      in brain. In situ hybridization showed that brain expression of LDP-4 was
      ubiquitous except for the hippocampus. When expressed in COS-7 cells, FLAG-tagged
      LDP-4 protein was present within the nucleus and Golgi apparatus. LDP-4
      expression did not reduce phosphorylation levels of MAPKs, but rather evoked
      activation of JNK and p38.

PMID- 17001451
TI  - FABPs as determinants of myocellular and hepatic fuel metabolism.
AB  - In vitro experiments and expression patterns have long suggested important roles
      for the genetically related cytosolic fatty acid binding proteins (FABPs) in
      lipid metabolism. However, evidence for such roles in vivo has become available
      only recently from genetic manipulation of FABP expression in mice. Here, we
      summarize the fuel-metabolic phenotypes of mice lacking the genes encoding heart
      type FABP (H-/- mice) or liver-type FABP (L-/- mice). Cytosolic extracts from H-/
      heart and skeletal muscle and from L-/- liver showed massively reduced binding
      of long chain fatty acids (LCFA) and, in case of L-/- liver, also of LCFA-CoA.
      Uptake, oxidation, and esterification LCFA, when measured in vivo and/or ex vivo,
      were markedly reduced in H-/- heart and muscle and in L-/- liver. The reduced
      LCFA oxidation in H-/- heart and L-/- liver was not due to reduced activity of
      PPARa, a fatty acid-sensitive transcription factor that determines the lipid
      oxidative capacity in these organs. In H-/- mice, mechanisms of compensation were
      partially studied and included a redistribution of muscle mitochondria as well as
      increases of cardiac and skeletal muscle glucose uptakes and of hepatic
      ketogenesis. In skeletal muscle, the altered glucose uptake included decreased
      basal but increased insulin-dependent components. Metabolic compensation was only
      partial, however, since the H-/- mice showed decreased exercise tolerance. In
      conclusion, the recent studies established H- and L-FABP as major determinants of
      regional LCFA utilization; therefore the H-/- and L-/- mice are attractive models
      for studying principles of fuel selection and metabolic homeostasis.

PMID- 17001452
TI  - Fatty acid-dependent expression of the muscle FABP gene - comparative analysis of
      gene control in functionally related, but evolutionary distant animal systems.
AB  - The heart is the most fatty acid-dependent muscle in mammals, but flight muscles
      of birds and insects encounter even higher rates of fatty acid oxidation. The
      amount of the muscle fatty acid binding protein (H-FABP) found in these muscle
      reflects their metabolic activities, and increased fatty acid metabolism in
      endurance exercise increases FABP expression further. We have studied the
      mechanism of fatty acid-dependent expression of the H-FABP gene, taking advantage
      of the comparative analysis of gene control in functionally related, but
      evolutionary distant animal systems, i.e., rat heart and locust flight muscle.
      Luciferase reporter genes with a full-length promoter ( approximately 1 kb) from
      either the locust or the rat were strongly expressed in L6 myoblasts, and the
      expression of both constructs was markedly increased by fatty acid treatment.
      Because of its stronger induction by fatty acids and the absence of other
      vertebrate transcription factor binding sites, the locust promoter was
      advantageous for the identification of a fatty acid response element (FARE), an
      inverted repeat of a hexanucleotide half site reminiscent of steroid hormone
      receptor binding sites (IR-3). All mammalian H-FABP promoters contain similar
      sequences, however in reverse orientation (everted repeats, ER-3). Deletion of
      the FARE eliminated the fatty acid inducibility completely for the locust
      promoter, but only partly for its mammalian analogue, perhaps because of
      additional factors or more complex interactions. In gel shift studies, the
      element binds nuclear proteins from both rat cells and locust flight muscle,
      further attesting to the far-reaching conservation of this mechanism. Two
      individual proteins bind to the element, with full binding requiring the presence
      of free fatty acid. Antibodies to PPARs failed to induce a supershift of the
      protein-DNA complex, indicating that other transcription factors are responsible
      for the fatty acid-mediated induction of gene expression of H-FABP.

PMID- 17001453
TI  - Amyand's hernia: a report of 18 consecutive patients over a 15-year period.
AB  - AIM: The presence of a vermiform appendix in an inguinal hernia sac is termed
      Amyand's hernia. It may present as a tender inguinal or inguino-scrotal swelling
      and is often misdiagnosed as an incarcerated or strangulated hernia. The purpose
      of this study was to review the management of Amyand's hernia at a single
      institution since 1991. MATERIAL AND METHODS: A retrospective analysis was
      undertaken of 18 consecutive patients with an Amyand's hernia operated upon at
      our institution from 1991 to 2005. Patients' demographics, treatment and
      postoperative outcome were analysed. RESULTS: There were 17 men and one woman.
      Their median age was 42 years. None of the patients was diagnosed preoperatively.
      The commonest presenting symptom was painful inguinal or inguino-scrotal swelling
      (83%). All patients, therefore, underwent emergency surgery with a presumptive
      diagnosis of either incarcerated or strangulated inguinal hernia. Operative
      findings included 11 normal appendices, four inflamed appendices and three
      perforated appendices in the inguinal hernial sac. Patients with a normal
      appendix (n = 11) had a mesh hernia repair without an appendicectomy. The rest of
      the patients (n = 7) with an abnormal appendix underwent emergency open
      appendicectomy followed by Bassini's sutured hernia repair. One patient died in
      the postoperative period of pneumonia. Only one recurrent hernia has been
      detected, with a median follow-up time of 6.4 years. CONCLUSION: The inflammatory
      status of the appendix determines the type of hernia repair and the surgical
      approach. Incidental appendicectomy in the case of a normal appendix is not
      favoured.

PMID- 17001454
TI  - Chronic perforation of the urinary bladder by self-inserted foreign body.
AB  - We report on a 14-year-old girl with pyelonephritis, secondary to a foreign body,
      in her urinary bladder. A self-inserted pencil led to stone formation and bladder
      perforation at two sites. Eighteen months after insertion, the pencil was removed
      by suprapubic cystotomy.

PMID- 17001455
TI  - Optimizing pelvic organ prolapse research.
AB  - For many years, researchers on this field have suffered from the lack of an
      efficient method for describing pelvic organ prolapse. Struggling to solve this
      problem, the International Continence Society has proposed a pelvic organ
      prolapse quantification (POP-Q) system [Bump RC, Mattiasson A, Bo K, Brubaker LP,
      DeLancey JO, Klarskov P, Shull B, Smith ARB, Am J Obstet Gynecol, 175(1):1956
      1962, 1996], which was validated as a precise and reproducible technique for
      describing pelvic organ position. However, even though very precise at describing
      pelvic organ position, our critic to this system is its limited ability to
      quantify the prolapse itself, since it still classifies prolapse into four
      grades, almost the same way as Baden and Walker did in 1972. As a result, the
      same grade can include a wide prolapse intensity range. The objective of this
      paper is to propose a method that makes POP research more efficient by directly
      measuring prolapse as a continuous variable that requires lesser number of
      subjects in order to achieve statistical significance.

PMID- 17001456
TI  - Pyometra and recurrent prolapse after Le Fort colpocleisis.
AB  - The Le Fort colpocleisis is a surgical option for advanced pelvic organ prolapse
      in elderly and infirm women who no longer desire coital function. It is thought
      that the creation of adequate lateral drainage channels will prevent the
      occurrence of a pyometra. The author describes the occurrence of a pyometra,
      despite adequate vaginal channels, necessitating hysterectomy. A 78-year-old
      woman presented with a 3-year history of purulent vaginal discharge that began
      shortly after an uncomplicated Le Fort colpocleisis. She also complained of
      recurrent symptomatic prolapse. Radiologic evaluation revealed a pyometra, which
      was confirmed at the time of laparotomy. At the time of hysterectomy, she
      benefitted from total colpocleisis, vaginectomy, and levator plication. The
      approach to recurrent prolapse after Le Fort colpocleisis is discussed. The
      occurrence of pyometra despite adequate drainage should affect how patients
      undergoing obliterative procedures for pelvic organ prolapse are counseled.

PMID- 17001457
TI  - Abstracts from the 27th Annual American Urogynecologic Society Scientific
      Meeting. 19-21 October 19-21, 2006. Palm Springs, California, USA.

PMID- 17001461
TI  - Treatment of neuroendocrine tumors with somatostatin analogs.
AB  - Neuroendocrine tumors constitute a group of hormone producing tumors originating
      from neuroendocrine cells in different organs. Most tumors have a low
      proliferation index measured by Ki67 and the progression of the tumor is slow.
      However, many patients suffer from endocrine symptoms induced by the hormones
      produced and released by the tumor cells. For some patients these symptoms can be
      life- threatening as in midgut carcinoid patients suffering from carcinoid crises
      with extensive flushes and hypotension or in patients with severe diarrhea
      induced by tumors producing vasointestinal polypeptide. In many other patients
      the hormone-induced symptoms interfere with the ability to carry out ordinary
      daily activities. The introduction of somatostatin analogs in the treatment of
      these hormone related symptoms has made it possible to control most of them and
      has added significantly to the quality of life for this group of patients.
      Unfortunately, the clinical inhibitory effect on tumor growth has not been very
      good with only 5-10% of the patients showing an objective response. However,
      stabilization of tumor growth may be achieved in a significant number of
      patients. In the future, the hope is that development of new somatostatin analogs
      with broader receptor-binding profiles will give us new analogs which are more
      efficient with regard to their antiproliferative effect. This possibility will be
      studied in future trials.

PMID- 17001462
TI  - Somatostatin receptor imaging for neuroendocrine tumors.
AB  - Tumors and metastases that express the somatostatin receptor subtypes sst2 sst3
      or sst5 can be visualized in vivo after injection of radiolabeled octapeptide
      somatostatin analogs, like (111)In-pentetreotide. (111)In-pentetreotide
      scintigraphy also allows for more accurate staging of the disease by
      demonstrating tumor sites, which were not shown by conventional imaging. (111)In
      pentetreotide scintigraphy may also detect resectable tumors that would have
      remained unrecognized using conventional radiological imaging techniques; it may
      prevent surgery with curative intent in those patients whose tumors have
      metastasized to a greater extend than could be detected with conventional
      radiological imaging and it may be used to select patients for treatment with the
      currently available octapeptide somatostatin analogs or with tumor targeted
      radioactive treatment with radiolabelled somatostatin analogs. (111)In
      pentetreotide scintigraphy has also been used to select patients with pituitary
      tumors for medical treatment with octapeptide analogs, but its clinical
      usefulness for this purpose seems to be limited. It further allows scar tissue to
      be differentiated from tumor recurrence after the pituitary surgery or
      radiotherapy. However, a large variety of lesions in and around the pituitary
      region also express somatostatin receptors and, therefore, can be visualized by
      (111)In-pentetreotide scintigraphy.

PMID- 17001463
TI  - Familial neuroendocrine tumor syndromes: from genetics to clinical practice.
AB  - Thanks to recent developments in molecular biology and cancer genetics, genetic
      testing has become widely available and useful in several kinds of familial tumor
      syndrome. However, the impact of genetic testing on medical management is not
      always straightforward. Clinicians have to consider the psychological impact and
      ethical complexities of communicating hereditary cancer risk information to
      families. This review notes some points on genetic counseling before and after
      genetic testing for familial neuroendocrine tumor syndromes.

PMID- 17001464
TI  - Pituitary pathology in patients with Carney Complex: growth-hormone producing
      hyperplasia or tumors and their association with other abnormalities.
AB  - First described in the mid 80's, Carney Complex (CNC) is a rare, dominantly
      heritable disorder with features overlapping those of McCune-Albright syndrome
      (MAS) and other multiple endocrine neoplasia (MEN) syndromes like MEN type 1 (MEN
      1). Pituitary tumors have been described in a number of patients with CNC; they
      present with elevated growth hormone (GH) levels and mild hyperprolactinemia.
      However, most patients with CNC have mild hypersomatomammotropinemia starting in
      adolescence; this is similar to the situation in MAS patients: in both disorders,
      pituitary hyperplasia appears to precede tumor development. Familial pituitary
      tumor syndromes such as CNC provide an important insight into the genetics and
      molecular pathology of pituitary and other endocrine tumors. Our understanding of
      these conditions is expanding rapidly due to the identification of the causative
      genes and the availability of murine disease models. The present report reviews
      the clinical findings related to pituitary tumor development among patients with
      CNC and provides an update on murine models of the complex.

PMID- 17001465
TI  - Current concepts in neuroendocrine cancer metabolism.
AB  - Neuroendocrine (NE) cancers occur in multiple anatomic locations and range in
      prognosis from indolent to aggressive. In addition, adenocarcinomas can express
      gene products associated with NE cells, referred to as NE differentiation (NED),
      which correlates with poor prognosis and aggressive disease. Several metabolites
      and peptides produced by NE cells have been discovered that engage in cellular
      signaling and have autocrine and paracrine effects on cancer cell proliferation.
      This review focuses on the current knowledge of small molecule metabolism in NE
      cancers involving the synthesis of biogenic amine, polyamine, and amino acid
      neurotransmitters. Systems biology-directed approaches to NE cancer metabolism
      using gene expression profiling, liquid chromatography/mass spectrometry (LC/MS)
      and nuclear magnetic resonance (NMR) are also discussed. Furthermore, knowledge
      of metabolic and signaling pathways in NE cancers has led to the successful
      implementation of therapeutic regimens in cell culture and animal models of NE
      carcinogenesis.

PMID- 17001467
TI  - Intravenous glutamine supplementation to head trauma patients leaves cerebral
      glutamate concentration unaffected.
AB  - OBJECTIVE: There is reluctance to use glutamine-containing i.v. nutrition for
      neurosurgical patients, as this may result in elevated intracerebral glutamate
      levels, which are thought to be associated with neuronal injury and cell
      swelling, causing an increase in ICP and an unfavourable outcome. As general ICU
      patients benefit from i.v. glutamine supplementation in terms of reduced
      mortality and morbidity, neurosurgical patients might also be candidates for such
      treatment, if the possible relation between i.v. glutamine supplementation and a
      possible increase in cerebral glutamate could be sorted out. DESIGN AND SETTING:
      The study protocol had a crossover design with a 24h treatment period and a 24h
      placebo period in random order. Treatment was a glutamine containing dipeptide, L
      alanyl-L-glutamine 200mg/ml, for 20h; placebo was saline. The rate of infusion
      was 0.125ml/kg/h, which is equal to 0.34g/kg of glutamine over the 20h period.
      Microdialysate was collected for analysis in 120min portions. The flow through
      the microdialysis catheter was 0.3microl/min. SUBJECTS: Patients with severe head
      trauma (GCS<or=8; n=15) on routine monitoring, including intracerebral
      microdialysis, were randomly assigned to treatment followed by placebo or placebo
      followed by treatment. MEASUREMENTS AND RESULTS: Glutamine infusion increased
      plasma glutamine concentration by 30%, but not plasma glutamate concentration.
      Intracerebral glutamate was unaffected in median values and in all individual
      patients. CONCLUSION: Intravenous glutamine in clinically relevant doses leaves
      cerebral glutamate unaffected. This opens the possibility of evaluating the
      effects of i.[Symbol: see text]v. glutamine supplementation upon outcome for
      neurosurgical ICU patients.

PMID- 17001466
TI  - Genes involved in neuroendocrine tumor biology.
AB  - The fascinating, but often unpredictable, biology of neuroendocrine tumors (NETs)
      make the management of these malignancies a real challenge. The more recent
      development of high-throughput genomic and proteomic techniques, have opened a
      window to an increased knowledge of the biology of NETs. This review will discuss
      genes thought to play a role in the context of NE tumor biology, with
      particularly attention to those that may be potential new diagnostic and
      prognostic markers, as well as therapeutic targets. NETs constitute a
      heterogeneous group of neoplasm that may arise in virtually every topographic
      localization in the body, as a consequence of malignant transformation of various
      types of NE cells. Since NETs arising in the gastroenteropancreatic (GEP) or
      bronchopulmonary system are by far the most common, this review focuses on these
      entities, but lines are drawn to other NETs as well. Although large-scale gene
      expression analysis undoubtly have raised interesting new hypothesis concerning
      genes thought to play a role in tumor biology, discrepancies observed between
      studies and various platforms used, emphasizes the need to not only standardize
      the way microarray data are reported, but also to introduce standards in sample
      taking, processing and study design. In addition, the recognition of the
      complexity of the human proteome, with regard to generation of multiple isoforms
      from one gene, has created additional challenges. However,some goals have been
      reached already, as new knowledge has been translated into development of novel
      promising therapeutics.

PMID- 17001468
TI  - Glucocorticoid signalling affects pancreatic development through both direct and
      indirect effects.
AB  - AIMS/HYPOTHESIS: Beta cell development is sensitive to glucocorticoid levels.
      Although direct effects of glucocorticoids on pancreatic precursors have been
      shown to control beta cell mass expansion, indirect effects of these hormones on
      pancreatic development remain unexplored. This issue was addressed in mice
      lacking the glucocorticoid receptor (GR) in the whole organism. MATERIALS AND
      METHODS: The pancreatic phenotype of GR(null/null) mice was studied at fetal ages
      (embryonic day [E]) E15.5 and E18 by immunohistochemistry and beta cell fraction
      measurements. To distinguish between direct and indirect effects, mutant E15.5
      fetal pancreata were grafted under the kidney capsule of immunodeficient mice and
      analysed after 1 week. RESULTS: E18 GR(null/null) fetuses had smaller digestive
      tracts and tiny pancreata. Massive pancreatic disorganisation and apoptosis were
      observed despite the presence of all cell types. E15.5 GR(null/null) mutants were
      indistinguishable from wild-type regarding pancreatic size, tissue structure and
      organisation, beta cell fraction and production of exocrine transcription factor
      Ptf1a, neurogenin 3 and Pdx-1. Grafting E15.5 GR(null/null) pancreata into a GR
      expressing environment rescued the increased apoptosis and mature islets were
      observed, suggesting that GR(null/null) pancreatic cell death can be attributed
      to indirect effects of glucocorticoids on this tissue. Heterozygous GR(+/null)
      mutants with reduced GR numbers showed no apoptosis but increased beta cell
      fraction at E18 and the adult age, strengthening the importance of an accurate GR
      dosage on beta cell mass expansion. CONCLUSIONS/INTERPRETATION: Our results
      provide evidence for GR involvement in pancreatic tissue organisation and
      survival through indirect effects. GR does not appear necessary for early phases,
      but its accurate dosage is critical to modulate beta cell mass expansion at later
      fetal stages, presumably through direct effects.

PMID- 17001469
TI  - Predictors, consequences and costs of diabetes-related lower extremity amputation
      complicating type 2 diabetes: the Fremantle Diabetes Study.
AB  - AIMS/HYPOTHESIS: The aims of this study were to assess the incidence, predictors,
      consequences, and inpatient cost of lower extremity amputation (LEA) in a
      community-based cohort of type 2 diabetic patients. METHODS: Between 1993 and
      1996, 1,294 patients with type 2 diabetes were recruited to the longitudinal,
      observational Fremantle Diabetes Study. LEAs and mortality from cardiac causes
      were monitored until 30 June 2005. Inpatient costs (in Australian dollars in year
      2000), derived using a case-mix approach, were available for the period from 1
      July 1993 to 30 June 2000. RESULTS: During follow-up 44 patients without LEA at
      baseline had a first-ever diabetes-related LEA, an incidence of 3.8 per 1,000
      patient-years. Independent predictors of first-ever LEA included foot ulceration
      (hazard ratio [95% CI]: 5.56 [1.24-25.01]), an ankle brachial index < or =0.90
      (2.21 [1.11-4.42]), HbA(1c) (increase of 1%: 1.30 [1.10-1.54]) and neuropathy
      (2.65 [1.30-5.44]). The risk of cardiac death was significantly increased in
      patients with LEA at baseline, although this was not an independent risk factor.
      The median (interquartile range) inpatient cost per LEA admission was 12,485
      Australian dollars (6,037 Australian dollars-24,415 Australian dollars), with a
      median length of stay of 24 (10-43) days. CONCLUSIONS/INTERPRETATION: First-ever
      LEAs in type 2 patients were associated with poor glycaemic control, foot
      ulceration and evidence of microvascular and macrovascular disease. Patients with
      LEA were at increased risk of cardiac death. LEAs contribute disproportionately
      to diabetes-related inpatient costs.

PMID- 17001470
TI  - Upregulation of adiponectin receptor 1 and 2 mRNA and protein in adipose tissue
      and adipocytes in insulin-resistant women with polycystic ovary syndrome.
AB  - AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is a multifaceted metabolic
      disease linked with insulin resistance (IR) and obesity. Adiponectin, which is
      lower in IR states, exerts its glucose-lowering and anti-inflammatory effects by
      activating two receptors, ADIPOR1 and ADIPOR2. There are no data on the relative
      expression of these receptors in adipose tissue of PCOS women. METHODS: We
      investigated the expression of adiponectin receptors from corresponding s.c. and
      omental (o.m.) adipose tissue in women with PCOS compared with matched non-PCOS
      women. As there is a disturbance in the steroid milieu in PCOS women, we also
      assessed the effects of testosterone and oestradiol on adiponectin receptors
      using adipocytes and adipocyte explants. Real-time RT-PCR and western blotting
      were used to assess the relative adiponectin receptor mRNA expression and protein
      production, respectively. Biochemical measurements were performed in our
      hospital's laboratory. RESULTS: We are the first to describe adiponectin receptor
      expression and production, in corresponding s.c. and o.m. human adipose tissues
      at the mRNA and protein level. We demonstrate the upregulation of mRNA expression
      and protein production of adiponectin receptors in women with PCOS, in s.c. and
      o.m. adipose tissue. Treatment of adipose tissue explants and adipocytes with
      testosterone and oestradiol induced the expression of adiponectin receptor mRNA
      and protein. There was a significant positive association between ADIPOR1/R2
      expression and homeostasis model assessment, testosterone, oestradiol and
      triglycerides and a negative relationship with sex hormone-binding globulin.
      CONCLUSIONS/INTERPRETATION: The precise reason for the upregulation of
      adiponectin receptors seen in PCOS women, a pro-diabetic state, is unknown, but
      it appears that sex steroids may play a role in their regulation in adipose
      tissue.

PMID- 17001471
TI  - Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as
      monotherapy in patients with type 2 diabetes mellitus.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess the efficacy and safety of
      sitagliptin (MK-0431) as monotherapy in patients with type 2 diabetes mellitus
      and inadequate glycaemic control (HbA(1c) > or =7% and < or =10%) on exercise and
      diet. METHODS: A total of 521 patients aged 27-76 years with a mean baseline
      HbA(1c) of 8.1% were randomised in a 1:2:2 ratio to treatment with placebo,
      sitagliptin 100 mg once daily, or sitagliptin 200 mg once daily, for 18 weeks.
      The efficacy analysis was based on an all-patients-treated population using an
      analysis of covariance, excluding data obtained after glycaemic rescue. RESULTS:
      After 18 weeks, HbA(1c) was significantly reduced with sitagliptin 100 mg and 200
      mg compared with placebo (placebo-subtracted HbA(1c) reduction: -0.60% and 
      0.48%, respectively). Sitagliptin also significantly decreased fasting plasma
      glucose relative to placebo. Patients with higher baseline HbA(1c) (> or =9%)
      experienced greater placebo-subtracted HbA(1c) reductions with sitagliptin (
      1.20% for 100 mg and -1.04% for 200 mg) than those with HbA(1c) <8% (-0.44% and 
      0.33%, respectively) or > or =8% to 8.9% (-0.61% and -0.39%, respectively).
      Homeostasis model assessment beta cell function index and fasting
      proinsulin:insulin ratio, markers of insulin secretion and beta cell function,
      were significantly improved with sitagliptin. The incidence of hypoglycaemia and
      gastrointestinal adverse experiences was not significantly different between
      sitagliptin and placebo. Sitagliptin had a neutral effect on body weight.
      CONCLUSIONS/INTERPRETATION: Sitagliptin significantly improved glycaemic control
      and was well tolerated in patients with type 2 diabetes mellitus who had
      inadequate glycaemic control on exercise and diet.

PMID- 17001472
TI  - The chemokine (C-X-C motif) receptor 4 inhibitor AMD3100 accelerates blood flow
      restoration in diabetic mice.
AB  - AIMS/HYPOTHESIS: Bone marrow cell mobilisation potently induces vascular growth
      in ischaemic tissue, possibly by mobilising endothelial cell progenitors. Thus,
      mobilising agents might not be therapeutic when endothelial cell progenitors are
      dysfunctional, as in diabetes mellitus. Local injection of autologous endothelial
      cell progenitors also stimulates vascular growth in ischaemic tissue, but
      endothelial cell progenitors from people with multiple cardiovascular risk
      factors and from obese diabetic mice are marginally therapeutic or inhibitory. We
      sought to identify possible strategies to improve vascularisation in patients
      with diabetes mellitus by determining if (1) mobilisation accelerates
      neovascularisation in diabetic animals, and (2) mobilised cells from a non
      diabetic source accelerate vascularisation in diabetic animals. METHODS: We
      tested whether systemic administration of the chemokine (C-X-C motif) receptor 4
      inhibitor AMD3100 or local injection of human CD34(+) circulating cells mobilised
      by AMD3100 could speed or enhance blood flow restoration in ischaemic limbs of
      diabetic mice. The small-molecule-mobilising drug AMD3100 was selected because
      mobilisation and apheresis can be done on the same day. RESULTS: Systemic
      administration of AMD3100 and local injection of cells mobilised by AMD3100
      greatly accelerated the restoration of blood flow to ischaemic limbs of diabetic
      mice. CD34(+) cells mobilised by AMD3100 appeared to be more potent growth
      stimulators than their unmobilised counterparts. CONCLUSIONS/INTERPRETATION:
      Unlike other mobilising agents requiring multi-day mobilisation, AMD3100 enables
      mobilised donors to undergo mobilisation and apheresis on the same day. The
      combination of excellent therapeutic benefits as well as ease of use indicates
      that AMD3100 could be a powerful tool to ameliorate tissue ischaemia in the
      diabetic environment.

PMID- 17001473
TI  - Genetic basis of murine responses to hyperoxia-induced lung injury.
AB  - To evaluate the effect of genetic background on oxygen (O2) toxicity, nine
      genetically diverse mouse strains (129/SvIm, A/J, BALB/cJ, BTBR+(T)/tf/tf,
      CAST/Ei, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ) were exposed to more than 99% O2
      for 72 h. Immediately following the hyperoxic challenge, the mouse strains
      demonstrated distinct pathophysiologic responses. The BALB/cJ and CAST/Ei
      strains, which were the only strains to demonstrate mortality from the hyperoxic
      challenges, were also the only strains to display significant neutrophil
      infiltration into their lower respiratory tract. In addition, the O2-challenged
      BALB/cJ and CAST/Ei mice were among six strains (A/J, BALB/cJ, CAST/Ei,
      BTBR+(T)/tf/tf, DBA/2J, and C3H/HeJ) that had significantly increased interleukin
      6 concentrations in the whole lung lavage fluid and were among all but one strain
      that had large increases in lung permeability compared with air-exposed controls.
      In contrast, the DBA/2J strain was the only strain not to have any significant
      alterations in lung permeability following hyperoxic challenge. The expression of
      the extracellular matrix proteins, including collagens I, III, and IV,
      fibronectin I, and tenascin C, also varied markedly among the mouse strains, as
      did the activities of total superoxide dismutase (SOD) and manganese-SOD (Mn-SOD
      or SOD2). These data suggest that the response to O2 depends, in part, on the
      genetic background and that some of the strains analyzed can be used to identify
      specific loci and genes underlying the response to O2.

PMID- 17001474
TI  - [A novel questionnaire to assess activity in patients after hip arthroplasties].
AB  - BACKGROUND: Until now, the activity of the lower limb could only be exactly
      measured with expensive electronic pedometers. The aim of this study was to
      develop a feasible questionnaire to measure the activity of patients after
      arthroplasty. METHODS: The "Daily Activity Questionnaire" (DAQ) was developed in
      several steps and the evaluation was carried out in three groups of patients with
      osteoarthritis of the hip (160 patients and 855 investigated days). The
      psychometric characteristics were verified. RESULTS: The retest reliability (ICC)
      of the DAQ is in a range comparable to the electronic pedometer StepWatch. The
      testing of the criterion validity showed high correlations between the StepWatch
      and the DAQ (r=0.743). CONCLUSION: Because of its high correlations to the load
      changes actually performed, the DAQ is especially suited to answer arthroplasty
      related questions. In all patient groups, projected load changes between 1.8 and
      2.4 million per year were found, which by far exceed the generally accepted test
      standards for endoprostheses.

PMID- 17001475
TI  - An experimental comparison of respiration measuring techniques in fermenters and
      shake flasks: exhaust gas analyzer vs. RAMOS device vs. respirometer.
AB  - Respiration measurement is applied as a universal tool to determine the activity
      of biological systems. The measurement techniques are difficult to compare, due
      to the vast variety of devices and analytical procedures commonly in use. They
      are used in fields as different as microbiology, gene engineering, toxicology,
      and industrial process monitoring to observe the physiological activity of living
      systems in environments as diverse as fermenters, shake flasks, lakes and sewage
      plants. A method is introduced to determine accuracy, quantitation limit, range
      and precision of different respiration measurement devices. Corynebacterium
      glutamicum cultures were used to compare an exhaust gas analyzer (EGA), a RAMOS
      device (respiration measurement in shake flasks) and a respirometer. With all
      measuring devices it was possible to determine the general culture
      characteristics. The EGA and the RAMOS device produced almost identical results.
      The scatter of the respirometer was noticeably higher. The EGA is the technique
      of choice, if the reaction volume is high or a short reaction time is required.
      The possibility to monitor cultures simultaneously makes the RAMOS device an
      indispensable tool for media and strain development. If online monitoring is not
      compulsive, the respiration of the investigated microbial system extremely low,
      or the sample size small, a respirometer is recommended.

PMID- 17001477
TI  - Multiplex PCR for the detection of toxigenic cyanobacteria in dietary supplements
      produced for human consumption.
AB  - The production of food supplements containing cyanobacteria is a growing
      worldwide industry. While there have been several reports of health benefits that
      can be gained from the consumption of these supplements, there have also been a
      growing number of studies showing the presence of toxins some of which (for
      example microcystins) are known to affect human health. In this paper, we report
      a multiplex polymerase chain reaction (PCR) technique that can be used to
      identify microcystin contamination in dietary supplements produced for human
      consumption. This method involves a PCR reaction containing three primer pairs,
      the first of which is used to amplify a 220-bp fragment of 16s rDNA specific to
      Microcystis, the most common microcystin-producing cyanobacterium. The second
      primer pair is used to amplify a 300-bp fragment of the mcyA gene, linked to
      microcystin biosynthesis in Anabaena, Microcystis, and Planktothrix. A third
      primer pair, used as a positive control, results in the amplification of a 650-bp
      fragment from the phycocyanin operon common to all cyanobacteria. This technique
      was found to be useful for detecting the presence of toxigenic Microcystis in all
      dietary supplements produced from the nontoxic cyanobacterium Aphanizomenon flos
      aquae.

PMID- 17001476
TI  - Seeing red primes tomato: evidence for comparable priming from colour and colour
      name primes to semantically related word targets.
AB  - There is ample evidence that an independent processing stream exists that
      subserves the perception and appreciation of colour. Neurophysiological research
      has identified separate brain mechanisms for the processing of wavelength and
      colour, and neuropsychological studies have revealed selective colour disorders,
      such as achromatopsia, colour agnosia, and colour anomia. The aim of the present
      study is to investigate whether the perception of colour may, despite its
      independent processing, influence other cognitive functions. Specifically, we
      investigate the possibility that the perception of a colour influences higher
      order processes such as the activation of semantically related concepts. We
      designed an associative priming task involving a colour prime (e.g. a red patch
      or the word RED) and a lexical decision response to a semantically related
      ('tomato' vs. 'timato') or unrelated ('grass' vs. 'griss') word target. The
      results of this experiment indicate that there is comparable facilitation of
      accessing colour-related semantics through the perception of a colour or the
      reading of a colour name. This suggests that colour has a direct effect on higher
      order level, cognitive processing. These results are discussed in terms of
      current models of colour processing.

PMID- 17001479
TI  - Localized Castleman's disease associated with systemic AA amyloidosis. Regression
      of amyloid deposits after tumor removal.

PMID- 17001478
TI  - RNAi-based tuning of cell cycling in Drosophila S2 cells--effects on recombinant
      protein yield.
AB  - We have demonstrated the RNA interference-based interruption of cellular
      controllers to increase recombinant protein yield in Drosophila Schneider 2 (S2)
      cell culture. Double-stranded RNA (dsRNA) was enzymatically synthesized in vitro
      and transfected into stable cell lines expressing green fluorescent protein (GFP)
      under an inducible promoter. Components of cell cycling (CycE and ago) were
      silenced with dsRNA homologous to a 700-nucleotide section of their respective
      mRNA transcripts. Silencing ago and CycE resulted in increases in product yield
      of up to 1.8-fold and 4-fold, respectively, relative to a control transfected
      with nuclease-free water. It is surprising to note that nearly complete silencing
      of CycE resulted in no significant change in GFP fluorescence after 24 h, and a
      decrease in fluorescence after 72 h. By partially silencing CycE, however, we
      were able to retain 80% of the cells in G1 (48-h sample) and increase GFP
      synthesis by fourfold. Implications for protein synthesis processing are
      discussed.

PMID- 17001480
TI  - The significance of the hemochromatosis genetic variants in multiple myeloma in
      comparison to that of myelodysplastic syndrome.
AB  - The clinical experience of the significant difference in iron metabolism between
      multiple myeloma and myelodysplasia prompted us to analyse patients according to
      mutation frequency in the hemochromatosis gene (HFE) known to participate in the
      regulation of iron metabolism. HFE genotyping results were also evaluated in view
      of the clinical data in multiple myeloma (MM) patients. 49 patients with MM were
      compared to 61 patients with myelodysplastic syndrome (MDS) concerning the
      incidence of two genetic variants of the HFE gene (C282Y and H63D) identified
      with PCR-RFLP. Data of serum iron, transferrin saturation, consumed blood units
      and initial white blood cell counts (WBC) were analysed in relation to the HFE
      genotype status. 30 out of the 61 MDS patients (49%) and only 9 out of the 49 MM
      patients (20%) were positive for either HFE variant. Serum iron and transferrin
      saturation levels were all normal in MM and elevated in MDS patients. The initial
      WBC were significantly lower in the minority of MM patients who were at the same
      time heterozygous for the HFE gene variants. We found significant differences in
      the frequencies of the HFE genetic variants between MDS and MM patients with
      strong correlation to their iron metabolism. The low WBC in HFE positive MM
      patients unrelated to bone marrow infiltration rate might raise the suspicion of
      co-existent myelodysplasia.

PMID- 17001481
TI  - Perineal lipomas associated with anorectal malformations.
AB  - Newborns with anorectal malformations may have associated perineal lipomas. These
      lesions are rare but may make the repair of the anorectal malformation more
      complex. Knowledge about the functional consequences of these lesions is scanty.
      The purpose of this study was to review the experience of anorectal malformations
      with perineal lipomas in two Scandinavian paediatric surgical centres. Six
      patients with perineal lipomas and anorectal malformation treated in the two
      centres from 1991 to 2005 were retrospectively reviewed. Bowel function was
      evaluated in patients more than 4 years old. Three girls and three boys (age 4
      months to 14 years) with anorectal malformations and perineal lipoma were
      included in the study. The boys all had high anorectal malformations with
      rectourethral or rectovesical fistulas. Two girls had a rectovestibular fistula
      and one girl had a cloaca. All patients had perineal lipomas, in one associated
      with an anterior meningocele. The lipomas were excised at time of anorectal
      reconstruction. One of the patients still has a colostomy, and two colostomies
      were recently closed. The bowel function was evaluated in three patients. Two
      patients have an ACE stoma to control constipation and soiling and one is soiling
      despite regular washouts. In conclusion, perineal lipomas associated with
      anorectal malformations are rare but may distort sphincter anatomy. Excision is
      best performed at time of anorectal reconstruction. Although our experience is
      limited, bowel function seems to be compromised by these lesions.

PMID- 17001482
TI  - Acute diverticulitis after Duhamel-Martin procedure for total colonic
      Hirschsprung's disease.
AB  - A 28-year-old man with a history of total colonic Hirschsprung's disease treated
      with a Duhamel-Martin procedure in infancy, presented with signs and symptoms of
      acute colonic diverticulitis. Flexible sigmoidoscopy demonstrated a 20 cm
      jejunocolonic anastomosis, consistent with his previous operation in childhood,
      with a large diverticulum at the proximal end of the anastomosis containing fecal
      concretions. The patient returned one month later after a course of antibiotics
      for definitive resection of the diverticulum. Intra-operative colonoscopy
      localized three large diverticula and resection of the involved segment was
      performed. The case is presented as an adult complication of total colonic
      Hirschsprung's disease treated with childhood resection and reconstruction.

PMID- 17001483
TI  - The epidemiology of pediatric falls from heights.

PMID- 17001484
TI  - The leaking pancreatic duct in childhood chronic pancreatitis.
AB  - The leaking pancreatic duct in childhood chronic pancreatitis presents with
      ascites and pleural effusion and is a potentially lethal condition. Seven
      children with this condition were seen in the period 2003-2006. The correct
      diagnosis was not entertained till a raised serum amylase was discovered. The
      diagnosis was confirmed by very high levels of amylase in the aspirated abdominal
      or pleural fluid. Computerized tomogram was the most useful imaging study and
      demonstrated a dilated pancreatic duct. All children were operated within 6 days
      of diagnosis by a Puestow's procedure in six and peripancreatic drainage in one.
      Six children made a prompt and lasting recovery after a Puestow's procedure while
      one child, also suffering from metastatic neuroblastoma, died in the immediate
      post operative period after peripancreatic drainage. We recommend prompt and
      definitive surgical management of this potentially lethal condition.

PMID- 17001485
TI  - Minimal access surgery for sigmoid volvulus in children.
AB  - A 12-year-old boy presented with large-bowel obstruction due to sigmoid volvulus.
      Temporary relief was achieved with rectal tube decompression. Elective
      laparoscopic-assisted sigmoid colectomy was performed. Post-operative recovery
      was uneventful. The patient remained well with no recurrence after 4 years of
      follow-up. Laparoscopic-assisted sigmoid colectomy may be the procedure of choice
      for selected children with sigmoid volvulus.

PMID- 17001486
TI  - Electrical stimulation and biofeedback exercise of pelvic floor muscle for
      children with faecal incontinence after surgery for anorectal malformation.
AB  - We report our experience of electrical stimulation and biofeedback exercise of
      pelvic floor muscle for children with faecal incontinence after surgery for
      anorectal malformation (ARM). Electrical stimulation and biofeedback exercise of
      pelvic floor muscle were performed on children with post-operative faecal soiling
      following repair of intermediate or high type ARM. Children under the age of 5
      years or with learning difficulties were excluded. They had 6 months supervised
      programme in the Department of Physiotherapy followed by 6 months home based
      programme. Bowel management including toilet training, dietary advice,
      medications and enemas were started before the pelvic floor muscle exercise and
      continued throughout the programme. Soiling frequency rank, Rintala continence
      score, sphincter muscle electromyography (EMG) and anorectal manometry were
      assessed before and after the programme. Wilcoxon signed rank test was performed
      for statistical analysis. From March 2001 to May 2006, 17 children were referred
      to the programme. Twelve patients (M:F = 10:2; age = 5-17 years) completed the
      programme. There was a trend of improvement in Rintala score at sixth month (p =
      0.206) and at the end of programme (p = 0.061). Faecal soiling was significantly
      improved at sixth month (p = 0.01) and at the end of the programme (p = 0.004).
      Mean sphincter muscle EMG before treatment was 1.699 microV. Mean EMG at sixth
      month and after the programme was 3.308 microV (p = 0.034) and 3.309 microV (p =
      0.002) respectively. After the programme, there was a mean increase in anal
      sphincter squeeze pressure of 29.9 mmHg (p = 0.007). Electrical stimulation and
      biofeedback exercise of pelvic floor muscle is an effective adjunct for the
      treatment of faecal incontinence in children following surgery for anorectal
      malformation.

PMID- 17001487
TI  - Functional outcome in correction of perineal fistula in boys with anoplasty
      versus posterior sagittal anorectoplasty.
AB  - Optimal surgical therapy for low anorectal anomalies remains controversial. We
      compared functional outcome after correction of perineal fistula in boys with
      either anoplasty (AP) or limited posterior sagittal anorectoplasty (PSARP).
      Thirty-nine boys from two centres treated for perineal fistula with either AP (n
      = 24) or PSARP (n = 15) from 1996 to 2001 underwent prospective follow-up for
      functional outcome. In order to minimize heterogeneity of the study groups, only
      boys with perineal fistula were included. Functional outcome was assessed using a
      validated bowel function score (maximum score 20). Day and night time wetting as
      well as the age at potty training were also recorded. An independent nurse
      specialist interviewed caregivers. AP and PSARP groups were comparable regarding
      age, associated malformations and frequency of sacral dysplasia. No significant
      differences between the groups were observed in the overall median bowel function
      score, AP 18 (11-20) versus PSARP 18 (11-20), or in the age at potty training, AP
      32 (14-66) versus PSARP 36 (18-60). Covering colostomy was employed significantly
      (P < 0.05) more often with PSARP (10/15) than with AP (1/24). Surgery for local
      complications was carried out significantly (P < 0.05) more often after PSARP
      (5/15) than after AP (2/24). Two patients in both groups required a temporary
      salvage colostomy. Overall functional outcome is comparable after AP and PSARP
      for perineal fistula in boys. As a more straightforward procedure AP is safer and
      less prone to complications avoiding the need for covering colostomy.

PMID- 17001488
TI  - Vagal neural crest contribution to the chick embryo cloaca.
AB  - Intrinsic innervation of the developing chick cloaca is provided by the enteric
      nervous system, a network of neurons and glia that lies within its walls. The
      enteric nervous system originates from neural crest cells that migrate from the
      vagal and sacral regions of the neural tube during the early stages of
      development. Abnormal cloacal development can cause a number of anorectal
      anomalies including persistent cloaca. Our study aimed to investigate the
      contribution of vagal neural crest cells to the total population of enteric
      neurons and glia within the chick embryo cloaca, using quail-chick chimeras.
      Chicken embryos were incubated until the 10-12 somite stage (ss). The vagal
      neural tube, corresponding to somites 1-7, was then microsurgically ablated in
      ovo and isochronic and isotopic quail grafts were performed. The eggs were then
      reincubated until embryos were harvested at E12. Whole embryos were fixed in
      Bouin's fluid, embedded in paraffin wax and sectioned. Immunohistochemistry was
      carried out using the HNK-1 antibody to label all neural crest cells, and the
      quail-specific antibody, QCPN, to label quail cells. QCPN-immunoreactive cells
      were seen to make up a large proportion of enteric neurons and glia within the
      walls of the embryonic cloaca. HNK-1 labelled all neural crest cells in the
      myenteric and submucosal plexuses as well as the sacral crest-derived nerve of
      Remak, while QCPN-positive cells were evident in both plexuses but mostly in the
      submucosal plexus, where they appeared to make up the majority of neurons.
      Results show that the chick embryo cloaca is primarily innervated by vagal neural
      crest cells. Further studies to investigate the contribution of sacral neural
      crest cells to the same region will give further insight into the development of
      the enteric nervous system within the embryonic cloaca.

PMID- 17001489
TI  - Enteric nervous system and developmental abnormalities in childhood.
AB  - ENS consists of a complex network of neurons, organised in several plexuses,
      which interact by means of numerous neurotransmitters. It is capable of
      modulating the intestinal motility, exocrine and endocrine secretions,
      microcirculation and immune and inflammatory responses within the
      gastrointestinal tract, independent of the central nervous system. Though the
      embryological development of various plexuses are completed by mid-way of
      gestation, the maturation of neurons and nerve plexuses appear to continue well
      after birth. Therefore, any histological or functional abnormalities related to
      the gastrointestinal function must be investigated with the ongoing maturational
      processes in mind.

PMID- 17001490
TI  - Cdk9 is an essential kinase in Drosophila that is required for heat shock gene
      expression, histone methylation and elongation factor recruitment.
AB  - Phosphorylation of the large RNA Polymerase II subunit C-terminal domain (CTD) is
      believed to be important in promoter clearance and for recruiting protein factors
      that function in messenger RNA synthesis and processing. P-TEFb is a protein
      kinase that targets the (CTD). The goal of this study was to identify chromatin
      modifications and associations that require P-TEFb activity in vivo. We knocked
      down the catalytic subunit of P-TEFb, Cdk9, in Drosophila melanogaster using RNA
      interference. Cdk9 knockdown flies die during metamorphosis. Phosphorylation at
      serine 2 and serine 5 of the CTD heptad repeat were both dramatically reduced in
      knockdown larvae. Hsp 70 mRNA induction by heat shock was attenuated in Cdk9
      knockdown larvae. Both mono- and trimethylation of histone H3 at lysine 4 were
      dramatically reduced, suggesting a link between CTD phosphorylation and histone
      methylation in transcribed chromatin in vivo. Levels of the chromo helicase
      protein CHD1 were reduced in Cdk9 knockdown chromosomes, suggesting that CHD1 is
      targeted to chromosomes through P-TEFb-dependent histone methylation.
      Dimethylation of histone H3 at lysine 36 was significantly reduced in knockdown
      larvae, implicating CTD phosphorylation in the regulation of this chromatin
      modification. Binding of the RNA Polymerase II elongation factor ELL was reduced
      in knockdown chromosomes, suggesting that ELL is recruited to active polymerase
      via CTD phosphorylation.

PMID- 17001492
TI  - Evaluation of a 12-week home-based walking intervention for breast cancer
      survivors.
AB  - GOALS OF WORK: To evaluate a 12-week home-based walking intervention among breast
      cancer survivors and to quantify changes in physical activity (PA) behaviors,
      body weight, and body composition in response to the intervention. PATIENTS AND
      METHODS: Breast cancer survivors that were in the posttreatment period were
      randomized to intervention (n=23) or wait-list usual care (n=13). PA was assessed
      by self-report, and in a study subsample (n=23), by an accelerometer. Intention
      to treat principles were employed to estimate the intervention effect on PA
      behaviors, body weight, and body composition. Intervention adherence was
      calculated as the proportion of exercise sessions completed relative to the
      number of exercise sessions recommended, as reported each week on walking logs.
      MAIN RESULTS: Thirty-four of 36 women randomized (94%) completed the study.
      Average intervention adherence over 12 weeks was 94%. Intervention participants
      reported a significantly greater increase in walking for exercise [+11.9
      metabolic equivalent (MET)-h/week] over time than did usual care participants
      (+1.7 MET-h/week, p=0.01). Objective measures of activity also indicated that
      intervention participants increased their activity levels over time as compared
      to usual care participants [i.e., counts/min/day and steps/day (p< or =0.04)]. No
      significant changes in body weight or composition were observed. CONCLUSION: We
      found that a 12-week home-based walking intervention was safe and effective for
      increasing short-term PA levels in breast cancer survivors. Future studies are
      needed to assess the ability of brief interventions to facilitate the maintenance
      of increased activity levels and to produce favorable quality of life and risk
      factor outcomes.

PMID- 17001493
TI  - Colour vision and visual ecology of the blue-spotted maskray, Dasyatis kuhlii
      Muller & Henle, 1814.
AB  - Relatively little is known about the physical structure and ecological
      adaptations of elasmobranch sensory systems. In particular, elasmobranch vision
      has been poorly studied compared to the other senses. Virtually nothing is known
      about whether elasmobranchs possess multiple cone types, and therefore the
      potential for colour vision, or how the spectral tuning of their visual pigments
      is adapted to their different lifestyles. In this study, we measured the spectral
      absorption of the rod and cone visual pigments of the blue-spotted maskray,
      Dasyatis kuhlii, using microspectrophotometry. D. kuhlii possesses a rod visual
      pigment with a wavelength of maximum absorbance (lambda(max)) at 497 nm and three
      spectrally distinct cone types with lambda(max) values at 476, 498 and 552 nm.
      Measurements of the spectral transmittance of the ocular media reveal that
      wavelengths below 380 nm do not reach the retina, indicating that D. kuhlii is
      relatively insensitive to ultraviolet radiation. Topographic analysis of retinal
      ganglion cell distribution reveals an area of increased neuronal density in the
      dorsal retina. Based on peak cell densities and using measurements of lens focal
      length made using laser ray tracing and sections of frozen eyes, the estimated
      spatial resolving power of D. kuhlii is 4.10 cycles per degree.

PMID- 17001495
TI  - Functional analysis of members of the isoflavone and isoflavanone O
      methyltransferase enzyme families from the model legume Medicago truncatula.
AB  - Previous studies have identified two distinct O-methyltransferases (OMTs)
      implicated in isoflavonoid biosynthesis in Medicago species, a 7-OMT methylating
      the A-ring 7-hydroxyl of the isoflavone daidzein and a 4'-OMT methylating the B
      ring 4'-hydroxyl of 2,7,4'-trihydroxyisoflavanone. Genes related to these OMTs
      from the model legume Medicago truncatula cluster as separate branches of the
      type I plant small molecule OMT family. To better understand the possible
      functions of these related OMTs in secondary metabolism in M. truncatula, seven
      of the OMTs were expressed in E. coli, purified, and their in vitro substrate
      preferences determined. Many of the enzymes display promiscuous activities, and
      some exhibit dual regio-specificity for the 4' and 7-hydroxyl moieties of the
      isoflavonoid nucleus. Protein structure homology modeling was used to help
      rationalize these catalytic activities. Transcripts encoding the different OMT
      genes exhibited differential tissue-specific and infection- or elicitor-induced
      expression, but not always in parallel with changes in expression of confirmed
      genes of the isoflavonoid pathway. The results are discussed in relation to the
      potential in vivo functions of these OMTs based on our current understanding of
      the phytochemistry of M. truncatula, and the difficulties associated with gene
      annotation in plant secondary metabolism.

PMID- 17001494
TI  - Imaging membrane potential in dendrites and axons of single neurons.
AB  - This review focuses on the use of imaging techniques to record electrical
      signaling in the fine processes of neurons such as dendrites and axons. Voltage
      imaging began with the use and development of externally applied voltage
      sensitive dyes. With the introduction of internally applied dyes and advances in
      detection technology, it is now possible to record supra-threshold action
      potential responses, as well as sub-threshold synaptic potentials, in fine
      neuronal processes including dendritic spines. The development of genetically
      coded sensors, as well as variants of laser scanning microscopy such as second
      harmonic generation, offers promise for further advances in this field. Through
      the use and further development of these methods, optical imaging of membrane
      potential will continue to be a valuable tool for investigators wishing to
      explore the electrical events underlying single neuronal computation.

PMID- 17001496
TI  - Molecular dissection of the interaction between the transcriptional activator
      ZmMRP-1 and the promoter of BETL-1.
AB  - The interaction between the transfer cell specific transcriptional activator
      ZmMRP-1 and the promoter of the transfer cell specific gene BETL-1 constitutes an
      exceptionally robust system. Reporter constructs containing the BETL-1 promoter
      are virtually silent in a variety of cell types, from maize leaves to yeast. The
      introduction of ZmMRP-1 in co-transformation assays leads to the transactivation
      of the reporter construct by up to two orders of magnitude. In this work we have
      investigated the molecular basis of this interaction. We found that the BETL-1
      promoter includes four potential targets for ZmMRP-1 binding, consisting of a 12
      bp motif containing two repeats. Co-transformation assays and electrophoretic
      mobility shift experiments identified the sequence TATCTCTATCTC as the preferred
      one for the interaction with the transcription factor. Identification of similar
      sequences in other transfer cell specific promoters lead us to propose as a
      transfer cell box a sequence related to those identified in the BETL-1 promoter,
      positioned 50-100 bp upstream the TATA box.

PMID- 17001497
TI  - Expressed sequence tags from loblolly pine embryos reveal similarities with
      angiosperm embryogenesis.
AB  - The process of embryogenesis in gymnosperms differs in significant ways from the
      more widely studied process in angiosperms. To further our understanding of
      embryogenesis in gymnosperms, we have generated Expressed Sequence Tags (ESTs)
      from four cDNA libraries constructed from un-normalized, normalized, and
      subtracted RNA populations of zygotic and somatic embryos of loblolly pine (Pinus
      taeda L.). A total of 68,721 ESTs were generated from 68,131 cDNA clones.
      Following clustering and assembly, these sequences collapsed into 5,274 contigs
      and 6,880 singleton sequences for a total of 12,154 non-redundant sequences.
      Searches of a non-identical amino acid database revealed a putative homolog for
      9,189 sequences, leaving 2,965 sequences with no known function. More extensive
      searches of additional plant sequence data sets revealed a putative homolog for
      all but 1,388 (11.4%) of the sequences. Using gene ontologies, a known function
      could be assigned for 5,495 of the 12,154 total non-redundant sequences with
      13,633 associations in total assigned. When compared to approximately 72,000
      sequences in a collated P. taeda transcript assembly derived from >245,000 ESTs
      derived from root, xylem, stem, needles, pollen cone, and shoot ESTs, 3,458
      (28.5%) of the non-redundant embryo sequences were unique and thereby provide a
      valuable addition to development of a complete loblolly pine transcriptome. To
      assess similarities between angiosperm and gymnosperm embryo development, we
      examined our EST collection for putative homologs of angiosperm genes implicated
      in embryogenesis. Out of 108 angiosperm embryogenesis-related genes, homologs
      were present for 83 of these genes suggesting that pine contains similar genes
      for embryogenesis and that our RNA sampling methods were successful. We also
      identified sequences from the pine embryo transcriptome that have no known
      function and may contribute to the programming of gene expression and embryo
      development.

PMID- 17001499
TI  - Nephropathology quiz page : Month/Year. Diagnosis: birefringent crystals
      consistent with chronic gouty nephritis.

PMID- 17001498
TI  - Anaemia correction in predialysis elderly patients: influence of the
      antihypertensive therapy on darbepoietin dose.
AB  - Anaemia and hypertension are common in patients with chronic renal insufficiency.
      The correction of anaemia with erythropoiesis stimulating agents (ESA) can
      improve survival and decrease the decline of renal function. Angiotensin
      converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (AIIRA)
      can also slow the progression of renal failure, but the blockade of the renin
      angiotensin system can worsen anaemia. The aim of our study was to assess the
      impact of antihypertensive therapy (ACEI plus AIIRA) in the requirements of
      darbepoietin in a group of elderly predialysis patients. We included 71 patients
      (m = 39, f = 32), mean age of 76.3 years with a mean creatinine clearance of 17.5
      ml/min. Patients were divided in two groups according to their antihypertensive
      therapy: G-I patients under ACEI or AIIRA therapy and G-II normotensive patients
      or hypertensive patients under antihypertensive drugs other than ACEI or AIIRA.
      The groups were compared regarding demographic, nutritional, biochemical and
      inflammatory parameters. We also compared the mean darbepoietin dose. In GI the
      mean dose of darbepoietin was higher than in GII (0.543 vs. 0.325 microg/kg/week,
      P = 0.032). We did not find any difference regarding other parameters analysed.
      We conclude that ACEI and AIIRA can increase the needs of darbepoietin in
      predialysis elderly patients. However, when formally indicated to treat
      hypertension in a specific patient, they should not be switched to another
      antihypertensive agent. Instead, in such cases, higher doses of ESA should be
      used, if necessary.

PMID- 17001500
TI  - Construction and characterization of a novel maltose inducible expression vector
      in Bacillus subtilis.
AB  - A maltose-inducible expression vector in Bacillus subtilis has been developed and
      characterized. The vector permitted beta-galactosidase expression at a high level
      (maximum activity, 8.16 U/ml) when induced and its expression was markedly
      repressed by glucose. Using this vector, we successfully expressed the other two
      genes, bioA and vgb. This thus provided a potential expression system for cloned
      genes in B. subtilis.

PMID- 17001501
TI  - Characterization of matrix metalloproteinase expressed by human embryonic kidney
      cells.
AB  - There is little information available on the proteases expressed by human
      embryonic kidney (HEK) cells, which are often used for expression of recombinant
      proteins and production of adenovirus vector. The expression profile of proteases
      in HEK cell line was investigated using zymography, mRNA analysis, western
      blotting and protein array. The major protease was gelatinase A [or matrix
      metalloproteinase (MMP)-2]. Beside, other MMPs, such as MMP-1, -2, -3, -8, -9, 
      10, -13 and membrane type (MT) 1- and 3-MMP, as well as tissue inhibitors of
      metalloproteinase (TIMP)-1, -2 and -3, were also expressed by HEK cells.
      Characterization of MMP and TIMP profiles expressed by HEK cells provides the
      basis for degradation control of recombinant protein and adenovirus vector during
      culture and purification processes.

PMID- 17001502
TI  - Total intravenous anesthesia/target-controlled infusion and auditory-evoked
      potentials in day surgery mammoplasty.
AB  - Total intravenous anesthesia and the new parameter for administering the most
      recent drugs, target-controlled infusion, as well as the introduction of new
      short half-life molecules that do not accumulate have made anesthesia in day
      surgery safer. In this study, the use of auditory-evoked potentials monitoring
      made it possible to determine the target plasma concentration of propofol that
      induces a narcosis sufficiently deep and strictly necessary for effectiveness,
      thus minimizing the anesthesiologic risk linked to the use and the dosing of the
      drug, reducing the hospitalization time, and decreasing the side effects for
      patients undergoing day surgery mammoplasty.

PMID- 17001505
TI  - Ecological data in Integrated Coastal Zone Management: case study of Posidonia
      oceanica meadows along the Corsican coastline (Mediterranean Sea).
AB  - Integrated Coastal Zone Management (ICZM) contributes towards maximizing the
      benefits provided by the coastal zone and minimizing conflicts and the harmful
      effects of activities upon each other. The coastal zone includes highly
      productive and biologically diverse ecosystems, but ecological data (including
      structure and processes) seem to be neglected. The purpose of this article is to
      present a case study of Posidonia oceanica meadows (seagrass beds) along the
      Corsican coastline (Mediterranean Sea) in order to exemplify the usefulness of
      ecological data to Integrated Costal Management programs. We will try to
      determine how the use of organisms could be enhanced. These investigations show
      the undoubted success of the Corsican Posidonia oceanica protection program, with
      a detailed description of the ICZM that precisely presents each component (e.g.,
      mapping, assessment of water quality, implementation of a system to aid decision
      making concerning the installation of new aquaculture units). This experience on
      the Corsican coasts could be used as an example in order to transfer to other
      locations in the Mediterranean Sea and/or to other target species.

PMID- 17001506
TI  - Use of remote-trip cameras for wildlife surveys and evaluating the effectiveness
      of conservation activities at a nature reserve in Sichuan province, China.
AB  - Monitoring the effectiveness of management activities within reserves is always a
      complicated task. When the focus of management activities is mammals, it is
      difficult to monitor their populations in a way that is rapid, effective, and
      inexpensive. We report on a mammal survey of a reserve in southwest China using
      remote-trip cameras. We surveyed 329 locations over 2 field seasons in 2002 and
      2003. Sixteen species of mammals were detected with these cameras, with four
      species documented for the first time. After accounting for variation due to
      slope, aspect, elevation, and habitat type, the distribution of six species was
      positively associated with the location of conservation stations and/or
      patrolling routes. Species of medium-sized mammals are excellent candidates for
      monitoring programs based on these cameras, due to their relative abundance,
      sufficient size to be detected by the camera units, and sensitivity to human
      activity. The distribution of mammals relative to management efforts is a
      relatively rapid means to assess reserve effectiveness. The repeat use of the
      cameras as part of a monitoring plan should provide a quantifiable measure of
      reserve effectiveness.

PMID- 17001507
TI  - Perceptions of prescribed burning in a local forest community in Victoria,
      Australia.
AB  - The general perceptions of prescribed burning were elicited from forest users for
      an area that has been subject to this form of land management for at least 20
      years. The largest group consisted of local residents living in and around the
      Wombat State Forest with two smaller groups of students from a nearby university
      campus and local professional land managers. A questionnaire was given to each
      participant in order to explore how the forest was used, to determine the level
      of knowledge of burning in the targeted forest and Victoria and the perception of
      the appearance, effectiveness of protection, and accessibility to the forest
      after prescribed burning. Generally all groups had similar responses with
      community members having stronger views on the effectiveness and practicalities
      of prescribed burning, whereas students were more neutral in their opinions. All
      participants claimed knowledge of prescribed burning activities within Victoria,
      but fewer had experience of planned fires in the Wombat State Forest. All groups
      agreed that areas that had not been recently burned had a better appearance than
      those that had, but this result may have included a range of value judgments.
      Land managers had a greater understanding of the ecological importance of season
      and timing of burning; however, some students and community members were equally
      knowledgeable. Prescribed burning did not impede access to the forest, nor did
      smoke from prescribed burns pose any great problem. The majority of the
      participants felt that the amount of prescribed burning done in the forest was
      adequate for engendering a feeling of protection to life and property, yet many
      were still suspicious of this management practice. These initial findings
      indicate several areas in which further research would be useful including the
      efficacy of education programs for community members and improved communication
      of burn plans by land managers.

PMID- 17001508
TI  - A system dynamics model for the environmental management of the Sepetiba Bay
      Watershed, Brazil.
AB  - In the recent past, the Sepetiba Bay watershed, located in the Rio de Janeiro
      State, Brazil has experienced rapid industrial development and population growth,
      as well as an increase in water pollution and environmental degradation. To
      analyze the complex interrelationships among the agents affecting the Sepetibza
      Bay environment, a system dynamics model was developed. The model builds on
      extensive studies conducted for the watershed, and simulates different hypotheses
      of economic growth and of demographic expansion. Thus, it can be used as a
      decision support tool for the identification of investment priorities and policy
      analyses under various scenarios. In order to provide a comprehensive approach to
      the environmental management of the Sepetiba Bay watershed, the model had to
      consider only the most relevant aspects of the behavior and the key interactions
      among agents operating in the watershed. In this article, the model's structure
      is presented together with some of its main results.

PMID- 17001509
TI  - Visitor evaluations of management actions at a highly impacted Appalachian Trail
      camping area.
AB  - Protected area management involves balancing environmental and social objectives.
      This is particularly difficult at high-use/high-impact recreation sites, because
      resource protection objectives may require substantial site management or visitor
      regulation. This study examined visitors' reactions to both of these types of
      actions at Annapolis Rocks, Maryland, a popular Appalachian Trail camping area.
      We surveyed visitors before and after implementation of camping policies that
      included shifting camping to designated newly constructed campsites and
      prohibiting campfires. Survey results reveal that visitors were more satisfied
      with all social and environmental indicators after the changes were enacted. An
      Importance-Performance analysis also determined that management actions improved
      conditions for factors of greatest concern to campers prior to the changes.
      Posttreatment visitors were least satisfied with factors related to reduced
      freedom and to some characteristics of the constructed campsites. Although there
      was evidence of visitor displacement, the camping changes met management goals by
      protecting the camping area's natural resources and improving social conditions.

PMID- 17001510
TI  - Comparison of angiogenic factor levels in tumor drainage and peripheral venous
      blood from colorectal cancer patients.
AB  - BACKGROUND: The main objective of this study was to determine whether there was a
      correlation in the levels of various angiogenesis-related factors between the
      tumor drainage and peripheral venous blood and whether appraisal of angiogenic
      factor levels in the tumor drainage venous blood could provide better prognostic
      information for patients with colorectal cancer than assessment of the peripheral
      venous blood. METHODS: Plasma levels of vascular endothelial growth factor
      (VEGF), basic fibroblast growth factor, and endostatin were measured and compared
      in both tumor drainage and peripheral venous blood from 52 patients with
      colorectal cancer. Plasma levels of angiogenesis-related factors were also
      correlated with tumor stage and clinical outcomes. RESULTS: The plasma endostatin
      level was significantly higher in peripheral blood than in tumor drainage venous
      blood (P < .001). The plasma VEGF level was significantly correlated with plasma
      endostatin levels (P = .028 in tumor drainage venous blood and P = .002 in
      peripheral venous blood). In both tumor drainage and peripheral venous blood, the
      VEGF level (but not the basic fibroblast growth factor or endostatin level) was
      significantly correlated with tumor stage and disease recurrence. However, in
      multivariate analysis, only plasma VEGF level in tumor drainage venous blood
      remained an independent predictor of disease recurrence. CONCLUSIONS: The plasma
      VEGF level in tumor drainage venous blood provided better prognostic information
      than that in peripheral venous blood. The plasma endostatin level was
      paradoxically significantly higher in peripheral than in tumor drainage blood,
      and this strongly suggests additional sources of endostatin in peripheral blood.

PMID- 17001512
TI  - Clinical and experimental approaches to the pathophysiology of interleukin-18 in
      cancer progression.
AB  - Interleukin-18 (IL-18, interferon [IFN]-gamma-inducing factor) is a
      proinflammatory cytokine converted to a biologically active molecule by
      interleukin (IL)-1beta converting enzyme (caspase-1). A wide range of normal and
      cancer cell types can produce and respond to IL-18 through a specific receptor
      (IL-18R) belonging to the toll-like receptor family. The activity of IL-18 is
      regulated by IL-18-binding protein (IL-18bp), a secreted protein possessing the
      ability to neutralize IL-18 and whose blood level is affected by renal function
      and is induced by IFNgamma. IL-18 plays a central role in inflammation and immune
      response, contributing to the pathogenesis and pathophysiology of infectious and
      inflammatory diseases. Because immune-stimulating effects of IL-18 have
      antineoplastic properties, IL-18 has been proposed as a novel adjuvant therapy
      against cancer. However, IL-18 increases in the blood of the majority of cancer
      patients and has been associated with disease progression and, in some cancer
      types, with metastatic recurrence risk and poor clinical outcome and survival.
      Under experimental conditions, cancer cells can also escape immune recognition,
      increase their adherence to the microvascular wall and even induce production of
      angiogenic and tumor growth-stimulating factors via IL-18-dependent mechanism.
      This is particularly visible in melanoma cells. Thus, the role of IL-18 in cancer
      progression and metastasis remains controversial. This review examines the
      clinical correlations and biological effects of IL-18 during cancer development
      and highlights recent experimental insights into prometastatic and proangiogenic
      effects of IL-18 and the use of IL-18bp against cancer progression.

PMID- 17001513
TI  - The mesenchyme in cancer therapy as a target tumor component, effector cell
      modality and cytokine expression vehicle.
AB  - Tissues and organs harbor a component of supportive mesenchymal stroma. The organ
      stroma is vital for normal functioning since it expresses factors instructing
      growth and differentiation along with molecules that restrain these processes.
      Similarly, the growth of tumors is strictly dependent on the tumor stroma. This
      review first discusses the possibility of developing tools to block the
      propagation of the tumor-associated stroma, that may halt tumor progression. It
      further describes how the tropism of mesenchymal stroma to tumor sites may be
      utilized to cause regression of the cancerous tissue. Mesenchyme can be
      genetically modified to overexpress specific regulatory molecules with known
      effects on specific tumors, such as interferon beta, studied in the context of
      melanoma and glioma and activin A, a transforming growth factor beta cytokine,
      examined in multiple myeloma. These studies point to the possibility that
      genetically modified mesenchymal cells may be used as a therapeutic modality for
      incurable human diseases. It is proposed that further development of methods of
      tumor stroma targeting, or alternatively the use of stromal mesenchyme as a cell
      or cell/gene therapy modalities, may yield novel clinical tools for the treatment
      of human cancers.

PMID- 17001514
TI  - Aberrant right hepatic sectoral duct injury following laparoscopic
      cholecystectomy: evaluation and treatment of a diagnostic dilemma.

PMID- 17001515
TI  - Double reactivity against actin and alpha-actinin defines a severe form of
      autoimmune hepatitis type 1.
AB  - Anti-filamentous actin antibodies characterize autoimmune hepatitis type 1 (AIH
      1). Recently, the binding domain of alpha-actinin on actin was shown to be a
      predominant epitope. To test this reactivity, an anti-alpha-actinin enzyme-linked
      immunosorbent assay was developed, and positivity confirmed by Western blot. Anti
      alpha-actinin antibody was found in 21/50 (42%) of AIH-1 patients, compared with
      52/401 (12.9%) of liver disease control patients, and with 6/200 (6%) of blood
      donors. Anti-filamentous and anti-alpha-actinin activities were found
      specifically together in 66% of anti-filamentous-positive AIH-1 patients. This
      combination of specificities reflected clinical and histological disease
      activity, short duration and absence of treatment. Finally, using an actin-alpha
      actinin complex assay, the binding of anti-filamentous actin to alpha-actinin
      binding domain on actin was demonstrated, as well as that of anti-alpha-actinin
      on the actin-binding domain of alpha-actinin. Thus, the frequent combination of
      anti-filamentous and anti-alpha-actinin antibodies seems to be the hallmark of
      activity in AIH-1.

PMID- 17001516
TI  - "It's like being in a labyrinth:" Hispanic immigrants' perceptions of depression
      and attitudes toward treatments.
AB  - This study aimed to describe Hispanic immigrants' perceptions of depression and
      attitudes toward treatments and to examine how demographics, acculturation,
      clinical factors, and past service use were associated with their perceptions and
      attitudes. A convenience sample of 95 Hispanic immigrant patients was presented a
      vignette depicting an individual with major depression. Structured interviews
      that included standardized instruments and open-ended questions were used to
      query patients about their views of depression and its treatments. Findings
      showed that Hispanic immigrants perceived depression as a serious condition
      caused by interpersonal and social factors. Consistent with existing literature,
      most patients endorsed positive attitudes toward depression treatments yet
      reported apprehensions toward antidepressants. Demographic factors,
      acculturation, depressive symptoms, and past mental health service use were
      related to patients' views of depression and attitudes toward care. This study
      emphasizes the need to incorporate Hispanic immigrants' perceptions and attitudes
      into depression treatments.

PMID- 17001517
TI  - A lipoxygenase inhibitor in breast cancer brain metastases.
AB  - The complication of multiple brain metastases in breast cancer patients is a life
      threatening condition with limited success following standard therapies. The
      arachidonate lipoxygenase pathway appears to play a role in brain tumor growth as
      well as inhibition of apoptosis in in-vitro studies. The down regulation of these
      arachidonate lipoxygenase growth stimulating products therefore appeared to be a
      worthwhile consideration for testing in brain metastases not responding to
      standard therapy. Boswellia serrata, a lipoxygenase inhibitor was applied for
      this inhibition. Multiple brain metastases were successfully reversed using this
      method in a breast cancer patient who had not shown improvement after standard
      therapy. The results suggest a potential new area of therapy for breast cancer
      patients with brain metastases that may be useful as an adjuvant to our standard
      therapy.

PMID- 17001518
TI  - Enhancement of pituitary adenoma cell invasion and adhesion is mediated by
      discoidin domain receptor-1.
AB  - The discoidin domain receptor-1 (DDR1) tyrosine kinases are a family of cell
      surface receptors that bind to several types of collagen and facilitate cell
      adhesion that is known association with several cancers. However, no previous
      study has examined the expression and function of DDR1 in pituitary adenoma.
      Tissue microarray analysis of DDR1 expression levels in 52 pituitary adenoma
      tissues revealed that DDR1 expression was significantly related to hormonal
      background (Kruskal-Wallis test; P < 0.0001). To further elucidate the function
      of DDR1 in pituitary adenoma, we developed DDR1 over- and under-expressing cell
      lines using DDR1 clone transfection and short interfering ribonucleic acids
      (siRNA)-based DDR1 gene silencing, respectively, in a human pituitary adenoma
      cell line (HP-75). Real-time reverse transcription-polymerase chain reaction (RT
      PCR) and Western blotting confirmed that expression of both DDR1 isoforms (DDR1a
      and DDR1b) was elevated by clone transfection and diminished by siRNA. Matrigel
      invasion assays revealed that cell invasion was increased in HP-75 cells over
      expressing DDR1 and decreased in cells under-expressing DDR1. Consistent with
      this, zymography revealed that the activation levels of matrix metalloproteinase
      (MMP)-2 and -9 were increased and decreased in cells over- and under-expressing
      DDR1, respectively. Examination of in vitro cell adhesion to collagen types I,
      II, III, and IV with respect to MMP-2 and -9 expression revealed that DDR1
      regulated cell adhesion to collagen type I, which was responsible for
      accelerating secretion of MMP-2 and -9 in DDR1 over-expressing cells. Taken
      together, these results strongly suggest that DDR1 mediates cell invasion-related
      signaling between collagen type I and MMP-2 and -9 in pituitary adenoma cells.

PMID- 17001519
TI  - Prognostic factors for anaplastic astrocytomas.
AB  - Anaplastic astrocytomas (WHO grade III) constitute about 10% of all gliomas.
      Definitive data on predictive and prognostic factors are lacking for these
      neoplasms that are considered the most enigmatic entity among the whole spectrum
      of astrocytic tumors because of their unclear biologic behavior and variable
      clinical outcome. Currently, only few factors have been identified as useful for
      prognosis of anaplastic astrocytoma: age and Karnofsky Performance Status.
      Attempts have been made to identify biological prognostic factors for response to
      therapy and clinical outcome, as well as potential targets for new therapies.
      Potential prognostic biomarkers concern tumor suppressor genes on chromosome 9q
      that are involved in the RB1 pathway; PTEN, the PI3k/Akt/p70s6k cascade, survivin
      gene, Formylpeptide receptor, minichromosome maintenance protein 3 and genes on
      chromosome 7. Furthermore, some angiogenic factors (e.g. hypoxia-inducible factor
      1alpha, vascular endothelial growth factor and scatter factor/hepatocyte growth
      factor) and the methylation status of O6-methylguanine-DNA methyltransferase gene
      (one of the main effectors of DNA repair system) are emerging novel putative
      determinants of prognosis. Moreover, recent studies on magnetic resonance imaging
      characteristics give prognostic significance to the presence of necrosis and
      enhancement. The state of the art pictured here underlie the recent interest on
      gene expression profile to identify aberrations useful to understand the biologic
      behavior of astrocytic tumors. Our knowledge in this field is still limited, and
      remains an issue of great concern.

PMID- 17001520
TI  - Disseminated medulloblastoma.

PMID- 17001521
TI  - Mothers' beliefs about knowledge, child development, and parenting strategies:
      expanding the goals of parenting programs.
AB  - This study examined the relationship between mothers' beliefs about knowledge
      (epistemology) and conceptions of child development and parent-child
      communication strategies. One hundred twenty mothers of preschool-aged children
      completed the Ways of Knowing measure and Parent Communication Strategies
      Interview; a subset of 38 also completed the Concepts of Development
      Questionnaire. Analyses revealed that mothers with more complex understanding of
      knowledge have less categorical and more multi-faceted conceptions of child
      development and are more likely to endorse parenting strategies that are less
      authoritarian and more cognitively challenging for children. EDITOR'S STRATEGIC
      IMPLICATIONS: Prevention programs designed to promote constructive parenting
      should foster parents' epistemological development (which guide beliefs and
      practices) rather than dwell on individual parent behaviors. The authors continue
      to develop the promising practice of tailoring interventions on the basis of
      parents' personal belief systems (see also Burns & Bond, 2004).

PMID- 17001522
TI  - Mapping and measuring social disparities in premature mortality: the impact of
      census tract poverty within and across Boston neighborhoods, 1999-2001.
AB  - The identification and documentation of health disparities are important
      functions of public health surveillance. These disparities, typically falling
      along lines defined by gender, race/ethnicity, and social class, are often made
      visible in urban settings as geographic disparities in health between
      neighborhoods. Recognizing that premature mortality is a powerful indicator of
      disparities in both health status and access to health care that can readily be
      monitored using routinely available public health surveillance data, we undertook
      a systematic analysis of spatial variation in premature mortality in Boston (1999
      2001) across neighborhoods and sub-neighborhoods in relation to census tract (CT)
      poverty. Using a multilevel model based framework, we estimated that the
      incidence of premature mortality was 1.39 times higher (95% credible interval
      1.09-1.78) among persons living in the most economically deprived CTs (>/=20%
      below poverty) compared to those in the least impoverished tracts (<5% below
      poverty). We present maps of model-based standardized mortality ratios that show
      substantial within-neighborhood variation in premature mortality and a sizeable
      decrease in spatial variation after adjustment for CT poverty. Additionally, we
      present maps of model-based direct standardized rates that can more readily be
      compared to externally published rates and targets, as well as maps of the
      population attributable fraction that show that in some of Boston's poorest
      neighborhoods, the proportion of excess deaths associated with CT poverty reaches
      25-30%. We recommend that these methods be incorporated into routine analyses of
      public health surveillance data to highlight continuing social disparities in
      premature mortality.

PMID- 17001523
TI  - Effects of a monoclonal anti-alphavbeta3 integrin antibody on blood vessels - a
      pharmacodynamic study.
AB  - PURPOSE: The integrin alphavbeta3 is an adhesion molecule expressed by
      proliferating endothelial cells and antibodies blocking this integrin inhibit
      angiogenesis in preclinical models. MEDI-522 is a second generation humanized
      anti-alphavbeta3 antibody designed for antiangiogenic therapy. The purpose of
      this study was to examine potential effects of this agent on blood vessels.
      EXPERIMENTAL DESIGN: In a phase I dose escalation study, MEDI-522 was
      administered by weekly infusions to 25 adult patients with advanced solid organ
      malignancies. As a surrogate angiogenesis assay, a wound was created by punch
      biopsy of the arm skin. This wound site was re-biopsied after a 7-day interval.
      Dual-label immunofluorescence experiments followed by computer-assisted image
      analysis were conducted to analyze the vasculature. RESULTS: Sequential
      pretreatment and 4-week treatment skin biopsy pairs were available on 4 patients,
      who had received 6 or 10 mg/kg of MEDI-522. MEDI-522 was detected in the dermal
      blood vessels as well as the dermal interstitium both in intact and wounded skin
      sites following treatment. No statistically significant difference was found
      between pretreatment and treatment samples of skin for vascular area, endothelial
      cell proliferation and apoptosis, or beta3 integrin levels. Phosphorylated focal
      adhesion kinase (pFAK) was significantly diminished in skin wound vessels during
      MEDI-522 treatment compared to the pretreatment samples. CONCLUSIONS: MEDI-522
      was detectable both in quiescent and in angiogenically active skin blood vessels
      as well as in the dermal interstitial space. The levels of pFAK were reduced
      during MEDI-522 treatment, suggesting a modulating effect on this signaling
      molecule.

PMID- 17001524
TI  - Applying a theory of change approach to interagency planning in child mental
      health.
AB  - This paper describes the use of a theory of change approach to community-based
      cross-agency service planning for children with serious emotional disturbance and
      their families. Public agency planners in Contra Costa County, California used
      the theory of change approach to organize service planning for a population of
      youth who had been arrested and involved with juvenile probation. The theory of
      change process described in this paper links community outcomes with planned
      activities with the assumptions or principles that underlie the community
      planning efforts. When complete, a theory of change logic model can serve as a
      guide for implementation, ensuring that community plans for service delivery
      remain true to their intent. The theory of change development process includes
      twelve stages and is based on a step-by-step approach. Theory of change logic
      models establish a context for articulating a community's shared beliefs and
      prompt local stakeholders to establish logical connections between the population
      to be served, expected results, and strategies intended to achieve those results.

PMID- 17001525
TI  - Positive emotion, negative emotion, and emotion control in the externalizing
      problems of school-aged children.
AB  - The present study examined the role of emotion and emotion control in children's
      externalizing problems. Third- to sixth-grade children were administered a self
      report measure of positive emotion, negative emotion, and emotion control. Peer-
      and teacher-reported adjustment problems were assessed. Structural equations
      modeling revealed that negative emotion, especially anger, was important in
      externalizing problems. Less positive emotion was associated with more
      externalizing problems. However, when negative emotion was examined in a more
      differentiated manner (anger, sadness and fear), the effect of positive emotion
      was diminished. Anger consistently emerged as a significant predictor of behavior
      problems. No interaction between either positive emotion and emotion control or
      negative emotion and emotion control was significant. Results showed main effects
      of each emotion component, with small interaction effects. Methodological and
      conceptual implications of the findings from the present study are discussed.

PMID- 17001526
TI  - Are there gender-specific pathways from early adolescence psychological distress
      symptoms toward the development of substance use and abnormal eating behavior?
AB  - The aim of the present longitudinal community study was to test whether
      psychological distress at 13 years of age predicted reported substance use
      problems in boys and abnormal eating behavior in girls 2 years later. The sample
      consisted of 500 male and 576 female students. The use of substances was
      evaluated using a semi-structured interview, psychological distress with the
      General Health Questionnaire (GHQ) and eating psychopathology with the Eating
      Attitudes Test (EAT-40), and the Bulimic Investigatory Test Edinburgh (BITE).
      Controlling the effect of initial substance use problems, psychological distress
      predicted later reported substance use problems in males. Girls with an initial
      score above the cut-off point on the GHQ were two times more likely to be at risk
      of having an eating disorder 2 years later. Therefore, psychological distress
      might take different developmental pathways in males and females, leading toward
      eating problems in the latter versus substance use in the former.

PMID- 17001527
TI  - Sleep disturbances and correlates of children with autism spectrum disorders.
AB  - This study examined sleep patterns, sleep problems, and their correlates in
      children with autism spectrum disorders (ASD). Subjects consisted of 167 ASD
      children, including 108 with autistic disorder, 27 with Asperger's syndrome, and
      32 with other diagnoses of ASD. Mean age was 8.8 years (SD = 4.2), 86% were boys.
      Parents completed a self-administered child sleep questionnaire. Results showed
      that average night sleep duration was 8.9 h (SD = 1.8), 16% of children shared a
      bed with parent. About 86% of children had at least one sleep problem almost
      every day, including 54% with bedtime resistance, 56% with insomnia, 53% with
      parasomnias, 25% with sleep disordered breathing, 45% with morning rise problems,
      and 31% with daytime sleepiness. Multivariate logistic regression analyses
      indicated that younger age, hypersensitivity, co-sleeping, epilepsy, attention
      deficit/hyperactivity disorder (ADHD), asthma, bedtime ritual, medication use,
      and family history of sleep problems were related to sleep problems. Comorbid
      epilepsy, insomnia, and parasomnias were associated with increased risk for
      daytime sleepiness. Results suggest that both dyssomnias and parasomnias are very
      prevalent in children with ASD. Although multiple child and family factors are
      associated with sleep problems, other comorbid disorders of autism may play a
      major role.

PMID- 17001528
TI  - Medical education for social justice: Paulo Freire revisited.
AB  - Although social justice is an integral component of medical professionalism,
      there is little discussion in medical education about how to teach it to future
      physicians. Using adult learning theory and the work of Brazilian educator Paulo
      Freire, medical educators can teach a socially-conscious professionalism through
      educational content and teaching strategies. Such teaching can model non
      hierarchical relationships to learners, which can translate to their clinical
      interactions with patients. Freirian teaching can additionally foster
      professionalism in both teachers and learners by ensuring that they are involved
      citizens in their local, national and international communities.

PMID- 17001529
TI  - Words and wards: a model of reflective writing and its uses in medical education.
AB  - Personal, creative writing as a process for reflection on patient care and
      socialization into medicine ("reflective writing") has important potential uses
      in educating medical students and residents. Based on the authors' experiences
      with a range of writing activities in academic medical settings, this article
      sets forth a conceptual model for considering the processes and effects of such
      writing. The first phase (writing) is individual and solitary, consisting of
      personal reflection and creation. Here, introspection and imagination guide
      learners from loss of certainty to reclaiming a personal voice; identifying the
      patient's voice; acknowledging simultaneously valid yet often conflicting
      perspectives; and recognizing and responding to the range of emotions triggered
      in patient care. The next phase (small-group reading and discussion) is public
      and communal, where sharing one's writing results in acknowledging vulnerability,
      risk-taking, and self-disclosure. Listening to others' writing becomes an
      exercise in mindfulness and presence, including witnessing suffering and
      confusion experienced by others. Specific pedagogical goals in three arenas
      professional development, patient care and practitioner well-being - are linked
      to the writing/reading/listening process. The intent of presenting this model is
      to help frame future intellectual inquiry and investigation into this innovative
      pedagogical modality.

PMID- 17001530
TI  - Efficacy and mechanisms of alpha-solasonine-and alpha-solamargine-induced
      cytolysis on two strains of Trypanosoma cruzi.
AB  - Two genetically diverse strains of Trypanosoma cruzi were tested in vitro for
      susceptibility to the solanum-derived triglycoside alkaloids solasonine and
      solamargine. Cytolytic assays were performed on epimastigotes (EMs) and
      bloodstream form trypomastigotes (BSFs) lifecycle stages by using serial
      dilutions of each alkaloid. Each alkaloid effectively lysed both lifecycle
      stages, although solasonine routinely required higher concentrations to induce
      similar results. EMs demonstrated greater resistance to cytolysis than BSFs at
      equal concentrations of either alkaloid. No significant resistance could be
      correlated to parasite strain. The reported synergistic cytolytic effects
      observed upon compounding solasonine and solamargine together were also tested.
      We failed to identify any cytolytic synergism in cultures of EMs or BSFs. The
      role of rhamnose-binding proteins (RBPs) in mediating cytolysis was investigated
      through competitive inhibition experiments. The addition of exogenous L: 
      rhamnose to the media failed to reduce parasite attrition independent of the
      parasite lifecycle stage. Based on these results, we suggest the mechanisms
      involved in cytolysis of T. cruzi by solasonine and solamargine are largely
      independent of rhamnose receptor-specific interactions. We propose that attrition
      likely involves less-specific carbohydrate interactions, which lead to the
      formation and intercalation of sterol complexes into the parasite plasma
      membrane.

PMID- 17001531
TI  - Volatile emissions from Aesculus hippocastanum induced by mining of larval stages
      of Cameraria ohridella influence oviposition by conspecific females.
AB  - Larval stages of the horse chestnut leafminer Cameraria ohridella can completely
      destroy the surface of horse chestnut leaves, Aesculus hippocastanum. This study
      investigated the effect of the degree of leaf browning caused by the insect's
      larvae on olfactory detection, aggregation, and oviposition of C. ohridella
      adults. The influence of A. hippocastanum flower scent on oviposition of the
      first generation was also evaluated. Utilizing gas chromatography coupled with
      parallel detection by mass spectrometry and electroantennography (GC-MS/EAD),
      more than 30 compounds eliciting responses from antennae of C. ohridella were
      detected. Oviposition and mining by C. ohridella caused significant changes in
      the profile of leaf volatiles of A. hippocastanum. After oviposition and
      subsequent mining by early larval stages (L1-L3), substances such as
      benzaldehyde, 1,8-cineole, benzyl alcohol, 2-phenylethanol, methyl salicylate,
      (E)-beta-caryophyllene, and (E,E)-alpha-farnesene were emitted in addition to the
      compounds emitted by uninfested leaves. Insects were able to detect these
      compounds. The emitted amount of these substances increased with progressive
      larval development. During late larval stages (L4, L5) and severe loss of green
      leaf area, (E,E)-2,4-hexadienal, (E/Z)-linalool oxide (furanoid), nonanal, and
      decanal were also released by leaves. These alterations of the profile of
      volatiles caused modifications in aggregation of C. ohridella on leaves. In
      choice tests, leaves in early infestation stages showed no significant effect on
      aggregation, whereas insects avoided leaves in late infestation stages. Further
      choice tests with leaves treated with single compounds led to the identification
      of substances mediating an increase or decrease in oviposition.

PMID- 17001532
TI  - Intraspecific competition, growth, chemistry, and susceptibility to voles in
      seedlings of Betula pendula.
AB  - We studied the effects of the intensity of intraspecific competition, as
      indicated by seedling density, and competitive success within populations, as
      indicated by seedling size, on the secondary chemistry of the stems of silver
      birch seedlings and their palatability to field voles. We found that the size of
      seedlings and their total phenolic concentrations were inversely related to stand
      density. Voles, however, did not discriminate between seedlings grown at the
      densities studied. Variation in competitive success was associated with several
      phenomena. Seedling size was positively related to the concentrations of several
      secondary compounds and to vole preferences, but negatively related to nitrogen
      concentration. We suggest that the ecological consequences of variation in
      seedling size cannot be predicted without knowledge of the mechanism behind the
      variation.

PMID- 17001533
TI  - Developmental trajectories in cottonwood phytochemistry.
AB  - We examined the hypothesis that ecologically important phytochemical traits
      differ predictably among various developmental zones of trees (i.e., mature and
      juvenile zones of individual trees and juvenile ramets that sprout from roots)
      and that the slope of this phytochemical gradient represents a "developmental
      trajectory." We focused on Populus fremontii (Fremont cottonwood), P.
      angustifolia (narrowleaf cottonwood), and their natural hybrids. Two major
      patterns emerged. First, within narrowleaf and hybrids, concentrations of
      important phytochemicals (condensed tannins and phenolic glycosides) differ
      greatly and predictably between developmental zones. Second, developmental
      trajectories differ greatly among these cottonwood species and their hybrids:
      Fremont exhibits a flat trajectory, narrowleaf a steep trajectory, and hybrids an
      intermediate trajectory, suggesting an additive genetic component and an
      ontogenetic basis to this phytochemical variation. Because diverse herbivorous
      species respond to the phytochemistry of their host plants, we predict that the
      developmental trajectories of plants play a major role in mediating ecological
      interactions and structuring communities, and that biodiversity in a stand of
      trees is determined by both interplant genetic diversity and intraplant
      ontogenetic diversity.

PMID- 17001534
TI  - Production and predator-induced release of volatile chemicals by the plant bug
      Lygus hesperus.
AB  - Both sexes of adult western tarnished plant bug, Lygus hesperus Knight
      (Heteroptera: Miridae), released three volatile chemicals in relatively large
      amounts when attacked by ants (Pogonomyrmex rugosus and Solenopsis xyloni) or
      when grabbed by forceps, as determined by solid-phase microextraction (SPME) and
      gas chromatography-mass spectrometry (GC-MS). The relative amounts of the
      volatile compounds, hexyl butyrate, (E)-4-oxo-2-hexenal, and (E)-2-hexenyl
      butyrate, absorbed by SPME as a percentage of the largest were 100%, 44%, and 4%,
      respectively, from females, and 83%, 37%, and 3% from males. Both ant species
      were repelled by the defensive discharges (confirmed by SPME) when the ants
      attacked L. hesperus adults. Sexually mature L. hesperus were individually
      extracted in pentane to quantify the mean amounts of hexyl butyrate (14.9
      microg/female; 10.3 microg/male), (E)-4-oxo-2-hexenal (2.7 microg/female; 3.1
      microg/male), and (E)-2-hexenyl butyrate (1.2 microg/female; 0.6 microg/male).
      (E)-4-Oxo-2-hexenal was unstable in solvent when in contact with a macerated
      adult, but relatively stable when the solution was decanted within minutes. The
      production of the three major volatile components began soon after the emergence
      of the adult and amounts increased for about 5-10 d with little or no increase
      thereafter. Minor additional constituents were cross-correlated in many cases
      with the three major ones. A cost of defensive secretion is suggested for females
      but not for males, because heavier females produced more volatile compounds than
      lighter females. The initial discharge percentage, defined as the proportion of
      volatile compounds initially present that is discharged to defend against
      predation was estimated at about 50% in males and 70% in females. Newly eclosed
      adults did not produce volatile chemicals until 2 d after molting.

PMID- 17001535
TI  - The impact of government decentralization on county health spending for the
      uninsured in California.
AB  - We analyze Program Realignment, California's 1991 policy of decentralizing
      control of health, mental health, and social services, from the state to the
      counties. Drawing from the economics literature on intergovernmental transfers
      and using data constructed for this study, we analyze the impact of Realignment
      on uninsured health spending. We find a change in the pattern of spending on
      indigent health services by counties following decentralization. Our results
      suggest, however, that county-level governments maintain a level of commitment to
      social-service spending that recent studies indicate may be lacking at the state
      level.

PMID- 17001536
TI  - Surgical management of mediastinal lesions.
AB  - Mediastinal tumors and cysts are relatively uncommon lesions requiring histologic
      confirmation. This retrospective study reports the experience of our department
      in the diagnosis and treatment of mediastinal lesions. Mediastinal lesions that
      were surgically treated in 200 patients aged 6-84 years, during a period of 28
      years, were included in this series. Sixty patients had an apparently non
      resectable lesion or lymphadenopathy of the anterior superior mediastinum. They
      had an anterior mediastinotomy and biopsy of the mediastinal lesion. No
      perioperative deaths were recorded in those patients. There were recorded 5
      (8.3%) complications. Histological diagnosis was established in all patients:
      lymphoma (n = 21), metastatic carcinoma (n = 16), thymic lesions (n = 10), germ
      cell tumor (n = 3), other lesions (n = 10). The remainder 140 patients underwent
      a resection of the mediastinal lesion. One (0.7%) perioperative death and 21
      (15%) complications were recorded. The histological diagnosis of the excised
      lesions was: thymic lesions (n = 60), neural tumors (n = 21), thyroid lesions (n
      = 14), bronchial cysts (n = 12), pericardial cysts (n = 10), germ cell tumors (n
      = 6), other lesions (n = 17). Our results are compared favorably with those
      reported in international literature. Surgery is the management of choice for
      patients with mediastinal lesions. It allows for establishing certain
      histological diagnosis and curative excision of the lesion, when it is necessary,
      with low operative risk.

PMID- 17001537
TI  - [Assessment of sleep with polysomnography in patients with interstitial lung
      disease].
AB  - In our study we aimed to examine the sleep structure, oxygenation and breathing
      pattern in interstitial lung disease (ILD) patients. We also aimed to determine
      whether relevance between the advanced disease and the sleep disorders exists and
      whether polysomnography is necessary in those patients. A total of 37 patients
      were examined in the study and whole night standard polysomnography was performed
      to all. Polysomnography results revealed that, total sleep time, time spent in
      NREM sleep stage III and IV, and in REM sleep were decreased. The patients had
      poor sleep efficiency and they spent more time as wake after sleep onset (WASO).
      Severe oxygen desaturations were detected during sleep and statistically
      significant positive correlations were found between mean awake O2 saturation and
      mean and lowest sleep O2 saturations. Clinical, Radiological and Physiological
      (CRP) scoring system was used to assess the disease stage, whether advanced or
      not, and statistically significant negative correlations were found between CRP
      score and awake and sleep O2 saturations. Obstructive sleep apnea syndrome (OSAS)
      was diagnosed in 24 (64.9%) patients. In those patients it was found that not the
      apneas but the hypopneas predominate. No difference was found among body mass
      indices (BMI) between the patients with and without OSAS. As a result it was
      concluded that a sleep study should be considered as part of the overall
      assessment in managing patients with ILD, and is especially indicated if there is
      incipient pulmonary hypertension, cor pulmonale and nocturnal arrhythmia despite
      normal awake blood gas tensions and symptoms as snoring and excessive day time
      sleepiness.

PMID- 17001538
TI  - [The effects of water-pipe, cigarette and passive smoking on mucociliary
      clearance].
AB  - We aimed to determine the effects of water-pipe smoking on lung mucociliary
      clearance system using radioaerosol ventilation scintigraphy and compare with
      cigarette and passive smoking and determine the level of exposure to tobacco
      smoke by measuring urinary cotinine in each group. Volunteer water-pipe only and
      cigarette only smokers from various cafes in Izmir city and passive smokers as
      control group were included in the study after exclusion and inclusion criteria.
      The ages, type of smoking, duration and daily amount of tobacco smoked and the
      medical histories of the volunteers were noted down. The pulmonary function tests
      (PFT), technetium-99m inhalation scintigraphy and urinary cotinine measurement
      with enzyme immunoassay (EIA) and were performed for each participant. Twenty
      water-pipe smokers, 23 cigarette smokers and 15 passive smokers were included
      into the study. There were no statistically significant differences among the
      mean ages, BMI and PFT parameters of all participants in study and control
      groups. Mucociliary clearance rates in terms of retention ratio after 1 hour and
      radioactivity half-life for each lung was lowest in the water-pipe smokers
      compared to others. Mucociliary clearance rate also decreased in the cigarette
      smokers compared to passive smokers. The differences in the mucociliary clearance
      rates among groups were statistically significant (p < 0.05). Urinary cotinine
      levels were highest in the cigarette smokers and higher in water-pipe smokers
      compared to passive smokers as statistically significant. As a conclusion
      mucociliary clearance rates decrease with tobacco smoking, being more prominent
      in water-pipe smokers in our study.

PMID- 17001539
TI  - [Comparison of computed tomography and magnetic resonance imaging to diagnose
      brain metastasis in non-small cell lung cancer].
AB  - To investigate the value of simultaneously obtained brain computed tomography
      (CT) and magnetic resonance imaging (MRI) to diagnose brain metastasis in non
      small cell lung cancer (NSCLC) patients with or without neurological symptoms.
      Sixty-two patients (58 male, 4 female) who were admitted to Yedikule Chest
      Hospital and Thoracic Surgery Center between January 2000-December 2003 and whom
      were diagnosed with NSCLC were included in the study. Ages of patients varied
      between 40-85 (61 +/- 11). All patients had hemogram and routine blood chemistry
      as well as chest X-ray, thorax CT, brain CT, brain MRI, FOB and a complete
      neurological exam. Brain metastasis were detected in 22 of 62 (35.5%) patients by
      using brain MRI and 16 (72.7%) of these hadn't had any neurological symptoms or
      signs. The difference to detect the brain metastasis between brain MRI and CT was
      statistically significant (p < 0.01). Nine of the 22 cases (14.5%) who were found
      to have brain metastasis by using MRI were stage I. While brain CT showed
      solitary brain metastasis in five patients, 4 (80%) of them were found to have
      multiple metastases when MRI studies were used. We concluded that, in an attempt
      to make correct staging and treatment of NSCLC and hence to investigate the brain
      metastasis in NSCLC patients including early stage ones, brain MRI is superior to
      brain CT study.

PMID- 17001540
TI  - [Factors affecting the prognosis in patients with primary lung cancer and brain
      metastases].
AB  - Brain metastases are frequent features during the course of patients with lung
      carcinoma. The aim of this study was to investigate prognostic factors for
      patients with brain metastasis from lung cancer. Eighty-eight patients with brain
      metastasis from lung cancer were enrolled in the study. Eighty-two of cases were
      male, six were female and the mean age was 57.5 +/- 10.4 years. The most common
      symptoms were headache (32.9%) and dizziness (32.9%). Fifty-two (59.1%) patients
      had solitary brain metastasis and the most frequent metastasing site was parietal
      lobe (34.1%). The median survival times were 3 months after diagnosis of lung
      carcinoma and 1.5 months after diagnosis of brain metastasis. Although the
      absence of brain metastasis at the moment of diagnosis, metachronous metastasis,
      central localization of the tumour, chemotherapy administration and surgical
      treatment of brain metastasis are good prognostic factors affecting survival
      after the diagnosis of lung carcinoma, the positive factors affecting survival
      after brain metastasis are central localization of tumour, chemotherapy
      administration and surgical treatment of brain metastasis. In conclusion,
      performing the combination of cranial radiotherapy, chemotherapy, surgical
      therapy and supporting therapy should be evaluated in all appropriate patients
      with brain metastasis from lung cancer.

PMID- 17001541
TI  - Risk factors and recurrence patterns in 203 patients with hemoptysis.
AB  - Management of hemoptysis requires prompt diagnosis and patient stabilization
      especially in massive hemoptysis as a potentially life-threatening condition.
      This retrospective study was designed to determine the etiologic distribution of
      hemoptysis, the role of the fiberoptic bronchoscopy (FOB) as a diagnostic tool,
      and to clarify potential risk factors for massive hemoptysis and recurrences. A
      total of 203 patients (181 male, 22 female) with hemoptysis admitted to our
      hospital were evaluated retrospectively. Tuberculosis was the leading cause of
      hemoptysis (n = 89; 43.8%) followed by lung cancer (21.7%) and chronic bronchitis
      (n = 11; 5.5%). FOB plays an essential role for localization of bleeding and
      diagnosis, although no bronchoscopic abnormality was found in our 31 patients
      (15.3%). Twenty-nine of the patients (14.3%) had recurrent hemoptysis and
      hemoptysis lasting longer than five days was found as a risk factor for
      recurrences (p = 0.02). Having lung cancer was an independent negative risk
      factor for recurrent hemoptysis using multivariate analysis (n = 44; p = 0.034).
      Twenty two of the patients (10.8%) had severe hemoptysis and managed medically.
      In our study, tuberculosis, lung cancer and heavy cigarette smoking were revealed
      as independent predictors of massive hemoptysis (p = 0.016, 0.001, 0.041
      respectively). Hemoptysis is a common respiratory symptom that always requires
      investigation by using FOB and radiography in order to determine exact site of
      bleeding and etiology. Hemoptysis continuing more than five days and lung cancer
      diagnosis may indicate recurrent bleeding and need more attention.

PMID- 17001542
TI  - [Microbiological results of bronchoalveolar lavage that was performed for
      opportunistic pulmonary infections].
AB  - Between 2001-2002; in 62 cases, 33 (53%) male, 29 (47%) female, mean age 51.4 +/-
      18.1 years) bronchoalveolar lavage (BAL) was performed for diagnosis of
      opportunistic pulmonary infection and specimens were evaluated for results of
      microbiological examinations. There was hematological malignancy in 18 (29%) and
      solid organ malignancy in 13 (21%) cases. Thirty-one (50%) cases were
      immunocompromised for reasons other than malignancy. By endoscopic evaluation
      endobronchial lesion was seen in 2 (3%) cases, indirect tumor signs were seen in
      2 (3%) cases and signs of infection were seen in 11 (18%) cases. Forty-even (76%)
      cases were endoscopically normal. Acid-fast bacilli (AFB) direct examination was
      positive in 3 (5%) cases. In 4 (6%) cases mycobacterial culture was positive,
      Mycobacterium tuberculosis-polymerase chain reaction (PCR) was also positive in
      these four cases. Examination of gram-stained smears for bacteria was associated
      with infection in 14 (23%) cases. Bacteriologic cultures were positive for single
      potential pathogen in 10 (16%) cases, and for mixed pathogens in 7 (11%) cases
      for a total number of 17 (27%). Fungal cultures were positive in 3 (5%) cases all
      of which had hematological malignancy. As a result in 24 (39%) cases
      microbiological agent of infection is determined: in four mycobacteria, in 17
      bacteria other than mycobacteria and in three fungi.

PMID- 17001543
TI  - Chlamydia and Mycoplasma serology in respiratory tract infections of children.
AB  - One of the challenges in planning the treatment of respiratory tract infection in
      children is identifying the causative agent. The objective of the present study
      was to investigate the incidence of Mycoplasma and Chlamydia in the etiology of
      respiratory tract infections of children. The present study included 100
      children, three months to 12 years of age, admitted to the outpatient department
      of pediatrics with such respiratory symptoms as fever, cough and respiratory
      distress. Following a detailed clinical history and physical examination,
      complete blood count, erythrocyte sedimentation rate, peripheral blood smear and
      chest X-ray were obtained from each patient. At admission, IgG and IgM for
      Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia
      psittaci were determined serologically. Positive antibody titer was found for
      Chlamydia and Mycoplasma in 18 (18%) of the patients. It was found that 2% of the
      patients had acute C. pneumoniae infection. When the subjects who had infections
      in the past or had re-infection were also considered; 6% were infected with C.
      pneumoniae, 3% with C. trachomatis, 1% with C. psittaci and 8% with M.
      pneumoniae. The presence of eosinophilia (> or = 4%) or the presence of siblings
      in the house were considered as factors favoring Chlamydial infections. High
      antibody titers for M. pneumoniae and C. pneumoniae were found more frequently
      after the age of two. Patients older than two years should be evaluated carefully
      for antibiotic treatments against atypical agents in pediatric lower respiratory
      tract infections.

PMID- 17001544
TI  - [The value of SF-36 questionnaire for the measurement of life quality in chronic
      obstructive pulmonary disease].
AB  - This study was performed in chronic obstructive pulmonary disease (COPD) patients
      to compare the SF-36 questionnaire with pulmonary function tests and non
      functional parameters. Fourty-five COPD patients diagnosed according to GOLD 2004
      criteria were included in the study. The stable patients were evaluated by
      spirometry, static lung volumes, diffusion capacity, 6 MWD, BORG scale, MMRC
      dyspnea measurement and SF-36 life questionnaire performed on the same day. The
      mean age of the patients was 66 +/- 10 years and the female/male ratio was 4/41.
      The mean FEV1/FVC ratio was 0.49 (moderate COPD n = 18, severe COPD n = 27). The
      RV/TLC ratio was 0.52. Walking distance was less than normal, with a mean of 375
      +/- 119 m. All the SF-36 scale except pain index are low compared to normal.
      General health perceptions, physical functioning, role physical, role emotional,
      social functioning, energy and mental health index are as follows: 47 +/- 24, 50
      +/- 30, 35 +/- 38, 49 +/- 37, 63 +/- 33, 49 +/- 20, 59 +/- 20, respectively. When
      the general health scale compared with FVC and FEV1 revealed moderate correlation
      was found (r = 0.56, r = 0.55, respectively). Physical functioning compared with
      FVC, FEV1, RV/TLC and IC revealed moderate correlation (r = 0.62, r = 0.67, r = 
      0.54, r = 0.65, respectively). General health and physical functioning scales
      correlated with the non-functional parameters (MMRC, 6 MWD) (r = -0.51, r = 0.53,
      r = -0.61, r = 0.64 respectively). The SF-36 general quality of life
      questionnaire is a useful measurement instrument for the evaluation of
      therapeutic efficiency and follow up of COPD patients.

PMID- 17001545
TI  - [Thoracic findings in neurofibromatosis].
AB  - Neurofibromatosis type 1 (von Recklinghausen' disease) is an autosomal dominant
      hereditary syndrome. It is characterized with multiple light brown (cafe-au-lait)
      spots, Lisch nodules and neurofibromas. Thorax and lungs are affected in various
      forms. Four cases with symptoms of thoracic involvement were investigated in our
      clinic. Mean age was 46. All cases had dyspnoea and cough; two of them had chest
      pain. Skin lesions of neurofibromatosis type 1 (NF 1) were pathologically
      confirmed in all cases. Moreover, case 3 had diffuse interstitial fibrosis and
      honeycomb pattern. Case 2 had thorax deformity, kyphoscoliosis and intrathoracic
      benign mass. Case 1 had two neurofibrosarcoma masses on the right hemithorax.
      Case 4 had multiple intrathoracic neurofibromas. Cases 1 and 3 died within two
      years after diagnosis due to malignancy and respiratory failure, respectively.
      Cases 2 and 4 are still under our control.

PMID- 17001546
TI  - Endobronchial hamartoma removed by flexible fiberoptic bronchoscopy via
      electrocautery.
AB  - Hamartomas are the most common benign tumors of the lung. It is most common
      peripherally in the parenchyma as solitary nodule or endobronchial lesion.
      Endobronchial form may cause obstruction of airway, atelectasis and recurrent
      pneumonia. Endobronchial hamartomas may be treated by surgical intervention or
      bronchoscopic excision (with rigid or flexible procedures). We are presenting a
      case of endobronchial hamartoma successfully treated with bronchoscopic
      electrocautery without a need for surgical removal.

PMID- 17001548
TI  - Pulmonary embolism in a patient with Klippel-Trenaunay-Weber syndrome.
AB  - Klippel-Trenaunay-Weber syndrome (KTWS) is a congenital disorder characterized by
      cutaneous capillary malformations, venous-lymphatic anomalies, hypertrophy of
      soft tissue and bone in the area of increased vascularity and arteriovenous
      fistulas with shunting. In this article we report the case of a 25 year old man
      with KTWS who had multiple surgical operations because of arteriovenous
      malformations. He admitted with pulmonary embolism attack to the hospital
      although he was taking prophylactic heparin treatment. We evaluate the risk of
      pulmonary embolism in patients with KTWS, being aware of the risk of deep venous
      thrombosis in progress of the disease and the importance of early diagnosis in
      prognosis.

PMID- 17001547
TI  - [Sinonasal NK/T-cell lymphoma mimicking Wegener's granulomatosis: a case report].
AB  - In Western population, sinonasal malignant lymphoma is rare and constitutes 1.5%
      of all non-Hodgkin lymphoma (NHL) and 2.2% of extranodal lymphomas. Wegener's
      granulomatosis (WG) is the necrotizing vasculitis of small arteries and veins. WG
      is characterized by granulomatous vasculitis and involves the upper and lower
      respiratory tract together with glomerulonephritis. But there are some forms of
      WG named limited WG that involves the upper respiratory tract only without
      glomerulonephritis and even seronegative without renal involvement. Herein, we
      present a typical WG with isolated sinonasal tract involvement with clinical, and
      radiological findings with the final diagnosis of NK/T-cell angiocentric lymphoma
      by the repeated biopsies. Since both diseases have same clinical and radiological
      findings differential diagnosis may be difficult.

PMID- 17001549
TI  - [Unusual foreign body aspiration].
AB  - Tracheobronchial foreign body aspiration in adults is rare when compared to
      children. In this case report, 76 year old female patient who aspirated a screw
      of tracheostomy cannula which was taken out by fiberoptic bronchoscopy (FOB) was
      presented. This case showed us that education of patients about stoma care is
      important. The FOB can be used safely to get foreign body from distal airways.

PMID- 17001550
TI  - [Inflammatory bowel disease and lung].
AB  - Ulcerative colitis and Crohn's disease are associated with a variety of systemic
      manifestations. Pulmonary disease has been described much less frequently than
      other organ systems, yet more than 400 cases have been reported. Lung and
      gastrointestinal system are originated from primitive gut and they have same
      pathogenetic changes in these patients. Major patterns of pulmonary disease
      associated with inflammatory bowel disease (IBD) are pleuritis, airway disease,
      interstitial lung disease, necrobiotic nodules, pulmonary eosinophilia,
      thromboembolic disease, vasculitis, granulomatous lung disease, etc. Colectomy
      may aggravate respiratory symptoms. Drug induced disease must be kept in mind in
      patients taking sulfasalazine, mesalamine, methotrexate, and anti-TNF-alpha.
      Latent pulmonary abnormalities are evident either at pulmonary function tests or
      induced sputum or bronchoalveolar lavage, have been also reported in patients
      with inflammatory bowel disease in the absence of clinical evidence of airway
      disease. The treatment of IBD related respiratory involvement depends on the
      specific pattern of involvement, if left untreated, especially in airway disease,
      puts the patient at risk of developing irreversible destruction of the air
      passage. A high degree of suspicion is necessary to detect early the respiratory
      disease in association with any form of bowel disease.

PMID- 17001551
TI  - Unexpectedly high prevalence of narcolepsy in Sivas.

PMID- 17001552
TI  - Pregnancy-associated rhinitis.
AB  - Previous studies overestimated the incidence of pregnancy-associated rhinitis
      because it is a poorly defined clinical condition. The objective of this study
      was to assess the incidence of this unique type of rhinitis using up-to-date
      strict criteria. This prospective study included 109 primigravida parturients who
      were interviewed using a structured questionnaire and underwent detailed
      rhinoscopy. Pregnancy-associated rhinitis was defined as nasal obstruction
      symptom and rhinorrhea appearing during pregnancy, lasting for at least 2 months,
      and disappearing postpartum. The incidence of rhinitis associated with pregnancy
      at the time of delivery was 9%. No correlation was found between symptoms and
      signs. Pregnancy-associated rhinitis is an infrequent clinical entity. It may be
      related to hormonal changes and possibly altered sensation of nasal airflow.

PMID- 17001553
TI  - Role of human placental efflux transporter P-glycoprotein in the transfer of
      buprenorphine, levo-alpha-acetylmethadol, and paclitaxel.
AB  - This study examines the role of placental P-glycoprotein (P-gp) in the transfer
      of buprenorphine (BUP) and L-alpha-acetylmethadol (LAAM) across the dually
      perfused human placental lobule. BUP (10 ng/mL) and LAAM (35 ng/mL) were perfused
      in the maternal-to-fetal direction. The following kinetic parameters were
      determined: fetal transfer rate (TR (f)), maternal clearance (Cl (m)), and
      clearance index (Cl (index)). The opiates were perfused in the presence of P-gp
      inhibitor GF120918 (experimental group) and in its absence (control group). The
      kinetic parameters for the control group were set at 100% and were as follows for
      LAAM in the experimental group: TR (f), 123 +/- 20%, Cl (m) 116 +/- 23%, and Cl
      (index) 123 +/- 22% ( P < 0.05). The corresponding parameters for BUP were not
      different from controls. The data indicate that LAAM, but not BUP, is extruded by
      the efflux transporter P-gp. Therefore, it is reasonable to assume that the
      activity of P-gp could be one of the factors affecting the extent of fetal
      exposure to LAAM during pregnancy.

PMID- 17001554
TI  - Extra-amniotic saline infusion increases cesarean risk versus other induction
      methods and spontaneous labor.
AB  - Extra-amniotic saline infusion (EASI) via a Foley catheter has been thought to be
      comparable in efficacy to other induction and cervical ripening methods. This
      study examines the risk of cesarean delivery associated with EASI compared with
      spontaneous labor and other methods of cervical ripening. A retrospective cohort
      study based upon deliveries at Bellevue Hospital Center from August 2000 to
      December 2002 was conducted. Three groups were identified: EASI, other methods of
      induction such as prostaglandins and oxytocin administration, and spontaneous
      labor. Pairwise comparisons were performed using analysis of variance and
      multivariate logistic regression analysis to control for confounding variables.
      There were 625 charts evaluated: including 171 with EASI, 190 with other
      induction methods, and 264 with spontaneous labor. The rates of cesarean section
      were 33.9%, 17.9%, and 7.2%, respectively. When compared with spontaneous labor,
      there was a higher risk of cesarean delivery for subjects induced with other
      methods (adjusted odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.5;
      P < 0.001), and for those induced with EASI (adjusted OR, 5.5; 95% CI, 3.1 to
      9.9; P < 0.001). When EASI was compared with other methods of induction, the risk
      of cesarean delivery was still increased (adjusted OR, 2.3; 95% CI, 1.4 to 3.8; P
      = 0.001). EASI is associated with an increased risk of cesarean delivery compared
      with spontaneous labor and other methods of cervical ripening.

PMID- 17001555
TI  - Shoulder dystocia at noninstrumental vaginal delivery.
AB  - This study examines the relationship between episiotomy and the occurrence of
      shoulder dystocia among noninstrumental vaginal deliveries. Analysis of data from
      a retrospective database was used to study noninstrumental vaginal deliveries in
      New Jersey during the years 1996 to 2001. The episiotomy group and nonepisiotomy
      group were analyzed separately using univariate and multivariate analysis. Among
      358,664 deliveries, rate of shoulder dystocia was 1.0% (n = 3596). Thirty-five
      percent of deliveries were assisted by episiotomy. Rate of dystocia was 1.42%
      with the use of episiotomy, and 0.81% when episiotomy was not used. This
      increased rate with episiotomy was noted across all of the racial groups, all
      birthweight categories, and all of the risk factor subgroups analyzed. There was
      a gradual decrease in the use of episiotomy from 37.30 to 26.03% without a
      corresponding increase in the rate of dystocia. Among noninstrumental deliveries,
      the rate of shoulder dystocia is higher in the episiotomy group. Decrease in the
      use of episiotomy has not resulted in an increase in the occurrence of dystocia.

PMID- 17001556
TI  - High-frequency oscillatory ventilation in term and near-term infants with acute
      respiratory failure: early rescue use.
AB  - This study describes a high-frequency oscillatory ventilation (HFOV) protocol for
      term and near-term infants with acute respiratory failure (ARF) and reports
      results of its prospective application. Neonates, with gestational age >or= 34
      weeks, were managed with HFOV, if required, on conventional ventilation (CV), a
      fraction of inspired oxygen (F IO(2)) 0.5, and a mean airway pressure > 10 cm H
      (2)O to maintain adequate oxygenation or a peak inspiratory pressure > 24 cm H
      (2)O to maintain tidal volume between 5 and 7 mL/kg of body weight. Seventy-seven
      infants (gestational age, 37 +/- 2,3 weeks), received HFOV after a mean duration
      of CV of 7.5 +/- 9.7 hours. Arterial blood gases, oxygenation index (OI), and
      alveolar-arterial difference in partial pressure of oxygen (P AO(2) - Pa O(2))
      were recorded prospectively before and during HFOV. There were a rapid and
      sustained decreases in mean airway pressure (MAP), F IO(2), OI, and P AO(2) - Pa
      O(2) during HFOV ( P <or= 0.01). Seventy infants (91%) were weaned successfully
      from HFOV. Seven infants (P AO(2) - Pa O(2) prior to HFOV, 601 +/- 89 mm Hg) were
      classified as having experienced treatment failure and died from their underlying
      disease. Treatment failure was associated with lack of improvement in P AO(2) -
      Pa O(2) at 1 hour of HFOV ( P < 0.01). Early rescue intervention with HFOV is an
      effective protocol for term and near-term infants with ARF. Failure to improve P
      AO(2) - Pa O(2) rapidly on HFOV is associated with HFOV failure. Randomized
      controlled trials are needed to identify benefits of HFOV versus conventional
      modes of mechanical ventilation.

PMID- 17001557
TI  - [Molecular diagnostic and targeted therapy--"Barking dogs are going to bite":
      presentations from the 42nd Annual Meeting of the American Society of Clinical
      Oncology, Atlanta 2006].
AB  - This years ASCO-meeting reinforced the trend of the recent years to get off from
      empirical treatment concepts to tailored and individualized diagnostics and
      therapy. However, the basis for an individual therapy is a specific molecular
      diagnostic which can be reflected in the analysis of hormonal receptor, HER-1,
      HER-2 and topoisomerase IIalpha in breast cancer. All these markers are not only
      able to prognosticate the course of disease but they also can predict the success
      of specific treatment approaches. Trastuzumab is standard therapy in HER-2
      positive breast cancer both in the adjuvant and palliative setting. But new
      therapeutic agents, as e. g. lapatinib, are promising in the treatment of HER-2
      positive breast cancer even if trastuzumab is failing. Otherwise it might
      possibly be an alternative option but adequate clinical results have to be
      awaited. The targeted inactivation of EGFR-related signal transduction pathways
      by e. g. gefitinib did not show a substantial improvement neither as a single
      agent nor in combination with endocrine treatment. However, the appropriate
      subgroup which might benefit from this therapy has to be defined even if
      molecular data suggest that patients with ER positive and PR negative breast
      cancer might be such a group. The increasing knowledge in terms of the biology of
      bone metastasis led to the development of new treatment options as e. g.
      denosumab, a humanized monoclonal antibody for RANK ligand. Two adjuvant
      cytotoxic treatment trials revealed that taxanes improve the prognosis of node
      positive breast cancer and should be administered sequentially. The advantage of
      switching to an aromatase inhibitor after two to three years of tamoxifen in
      endocrine treatment of postmenopausal patients is proved by two clinical trials
      (IES, ARNO) which could demonstrate a survival benefit. In conclusion it seems to
      be evident that new targeted therapy options are effective and will set new
      standards for the treatment of breast cancer patients in the near future. The
      presentation for the ovarian cancer focused on the addition of a third cytotoxic
      agent to carboplatin and paclitaxel as the standard therapy for the primary
      treatment of ovarian cancer. New data of Bevacizumab in the treatment of primary
      and recurrent ovarian cancer were presented. However, this is not yet a standard
      treatment for all patients and needs further investigations within large,
      multicentre, randomised trials. The lymphonodectomy as part of the primary
      therapy of the endometrial cancer seems to be a benefit at least in patients with
      advanced disease or high risk stage I tumours. The adjuvant therapy of uterine
      sarcomas is still not yet very well investigated and clear. A trial which
      recruited 12 years demonstrated a benefit in overall survival which has to be
      interpreted with caution. In this year again there have been registered an
      increasing number of interesting contributions from Germany, which also received
      international attention.

PMID- 17001558
TI  - [Cervical cancer screening of HIV-positive women: is a prolongation of the
      screening interval meaningful?].
AB  - OBJECTIVE: Cervical cancer screening guidelines stated recently that the
      screening interval of healthy women can be extended up to 3 years. Can those
      recommendations be applied for high risk populations? MATERIAL AND METHODS: In a
      prospective setting 305 HIV-positive women have been enrolled in this analysis
      between September 2000 and December 2003. Patients have been characterized
      according to HPV (human papilloma virus) prevalence, CIN (cervical
      intraepithelial neoplasia) incidence and CD4 cell count. RESULTS: 41 % of all HIV
      positive women were HPV positive (oncogene subtypes). In patients with diminished
      CD4 cells the HPV prevalence increased to 60 % (54/90). CIN was found in 27 %
      (83/305) women. CIN was more frequent by HPV-positive women with a CD4 cell count
      < 200 mm (3) (52 %, 38/72). The CIN incidence was also high in HIV-positive women
      with negative HPV infection and diminished CD4 cell count (39 %, 7/18 vs.7 %,
      11/161). CONCLUSIONS: The current cervical cancer screening guidelines are not
      helpful in HIV-positive women. The CIN incidence is significantly higher as in
      the HIV-positive population. For this reason this high risk population as e. g.
      HIV-infected women need an intensive care of diagnostic tools and short screening
      intervals to detect CIN.

PMID- 17001559
TI  - [Diagnostic and preoperative staging of endometrial carcinoma with transvaginal
      sonography--a review].
AB  - Endometrial carcinoma is the most common malignant tumor of the female genital
      tract. The major non-invasive diagnostic method is ultrasound. Endometrial
      thickness (double layer) is measured by transvaginal sonography. The cut-off
      value in patients with postmenopausal bleeding is still controversial, although
      in patients with endometrial thickness below 4 mm (or 5 mm respectively),
      malignancy can be excluded with high probability. If the endometrium measures
      more than 4 mm (or more than 5 mm respectively) or the patient presents with
      continuous bleeding, hysteroscopy and curettage should be performed in order to
      obtain histologic diagnosis. Sonographic findings like structure and demarcation
      of the endometrium increase diagnostic specificity only when combined with the
      measurement of endometrial thickness. Measuring the fluid within the uterine
      cavity does not seem to be useful in differentiating malignant from benign
      disorders. The extent of surgery depends on the preoperative estimation of the
      tumor stage which is particularly important for elder patients with increased
      morbidity. Transvaginal sonography has not been widely accepted to predict the
      depth of myometrial invasion or cervical infiltration. Although promising studies
      exist, additional examinations have to be done in order to determine the role of
      transvaginal sonography beside other methods (CT, MRT). This article on
      transvaginal ultrasound reviews current data on the method's capacity to identify
      endometrial cancer and to diagnose the depth of invasion.

PMID- 17001560
TI  - [Clinical impact of locoregional hyperthermia in gynecological oncology].
AB  - In the last decade progress in gynecological oncology has been achieved mainly by
      new cytotoxic drugs and advances in radiation technology. For example, the use of
      taxanes in the primary therapy of ovarian cancers and of combined radio
      chemotherapy in cervical cancer has led to significant prolongations of survival.
      However, in case of relapse most gynaecological malignancies are associated with
      very poor prognosis. Efficacy of local and systemic therapy can be increased by
      combining radiotherapy and/or chemotherapy with locoregional hyperthermia (LRH).
      Increasing the temperature of the target tissue up to 41-43 degrees C leads to
      local hyperaemia and the tumor tissue becomes more responsive to cytotoxic
      interventions. In several prospective randomized studies the combination between
      LRH and radiotherapy was superior to radiotherapy alone in terms of local control
      (e. g. chest wall recurrence in breast cancer) and has led to longer overall
      survival in advanced cervical cancer. Platinum derivatives and other cytotoxic
      drugs have shown synergistic effects with LRH and the combination of both has
      elicited high response rates in recurrent cervical cancer. In phase-II-clinical
      trials the newly developed liposomal anthracyclines demonstrated synergistic
      effects with LRH in patients with refractory ovarian cancer. Our own experience
      has shown that adding LRH to radio- and/or chemotherapy is well tolerated by the
      patients. Despite of the fact, that the available data are still preliminary, the
      inclusion of LRH into multimodal cancer therapy concepts appears to be very
      promising. Well-designed comparative studies are still needed to evaluate the
      role of hyperthermia as an adjunct to conventional cancer therapy.

PMID- 17001561
TI  - [Maggot therapy in gynecology].
AB  - Ancient societies recognised beneficial effects of certain fly larvae on wound
      healing. Nowadays, biosurgery with living maggots has proven very useful in the
      therapy of infected, necrotic, acute and chronic wounds. The larvae cause a rapid
      and selective wound debridement, a disinfective effect and rapid formation of
      granulation tissue and epithelium. In our hospital, we gathered experience in
      wounds caused by gynecological surgery. Here, maggot therapy has been used in
      locations--e. g. perineal--which are difficult to provide with hydrocolloid wound
      dressings. Maggots can clear wounds of staphylococci and streptococci
      populations, are successful in wounds caused by radiation therapy and can be used
      after chemotherapy. Patient acceptance is very high and psychological stress has
      been rare. Maggot therapy is a cheap, safe and highly effective treatment of
      wounds. Therefore, we want to encourage the use of biosurgery in suitable wounds.

PMID- 17001562
TI  - Different T-cell receptor (TCR) zeta chain expression in cervical cancer and its
      precursor lesions.
AB  - OBJECTIVE: Cervical cancer is associated with infection of epithelial cells with
      the human papillomavirus (HPV) type 16 and HPV18. A functional signalling
      machinery in T-cells is required in order to successfully fight and eradicate
      HPV16+ transformed epithelial cells. One of the key signalling molecules
      associated with the T-cell receptor (TCR) is the homodimeric zeta chain molecule.
      MATERIAL AND METHODS: 28 formalin fixed und paraffin embedded samples of cervical
      tissue with cervical intraepithelial lesions CIN I (n = 3), CIN III (n = 7),
      invasive cervical carcinoma (CC) (n = 13) and normal cervical tissue (n = 5) has
      been evaluated for HPV-PCR und zeta chain immunohistochemistry. For
      immunohistochemistry a monoclonal IgG1 anti TZR zeta chain-antibody (mAb) has
      been used (clone 6B 10.2, Santa Cruz, Heidelberg, Germany). According to the
      performed Western-Blot analysis on peripheral blood monocytes (PBMCs) the used
      mAb has specifically recognized TCR zeta chains. RESULTS: We show reduced protein
      zeta chain expression associated with invasive cervical cancer, but not with pre
      invasive HPV16-positive lesions or HPV16-negative normal cervix tissue.
      CONCLUSIONS: Thus, reduced TCR zeta chain expression is not necessarily linked to
      a chronic viral infection, nor to the presence of transformed cells, but rather
      to the stromal invasion of the cancer lesion.

PMID- 17001563
TI  - [Squamous cell carcinoma in neovagina at Mayer-Rokitansky-Kuster-Hauser
      syndrome].
AB  - Carcinoma of the vagina is a rare entity of cancer, also a primary carcinoma of
      the neovagina in patients with vaginal agenesia is of rare occurrence. CASE
      REPORT: We report on a 48-year-old female patient with a squamous cell carcinoma
      in neovagina after Mayer-Rokitansky-Kuester-Hauser-syndrome. Neovagina was
      constructed by method of Vecchietti 28 years before. Operative treatment
      consisted of anterior exenteration with construction of a modified Mainz-1-pouch.
      There were no complications intra- or postoperative. Microscopic findings showed
      a G2-differentiated invasive squamous cell carcinoma of the neovagina at stage
      FIGO III with an infiltration of urethra and the bladder neck. The tumor could be
      resected completely, no infestation of lymph nodes was observed. In the further
      process the aftercare is planned. In a systematic literature review 19 female
      patients with a primary carcinoma of neovagina after agenesia of vagina could be
      identified. CONCLUSIONS: Female patients with a neovagina require a regular
      gynaecologic examination in order not to survey a malignant transformation
      although a malignoma in neovagina is rare. A possible therapy option is the
      radical operation, there are no data of long-term prognosis at present.

PMID- 17001564
TI  - An evaluation of emergency sclerotherapy of varices in randomized trials: looking
      the needle in the eye.
AB  - BACKGROUND: The role of sclerotherapy for acute variceal bleeding is challenged
      by vasoactive drugs and by ligation. AIM: A meta-analysis was performed to
      evaluate whether sclerotherapy remains a gold standard in acute variceal
      bleeding. METHODS: Sclerotherapy was evaluated across four randomized trial
      groups: (a) combined with vasoconstrictors vs. vasoconstrictors alone (five
      trials, with 400 patients); (b) vs. vasoconstrictors alone (15 trials, with 1296
      patients); (c) vs. combination of vasoconstrictors and sclerotherapy (eight
      trials, with 1026 patients); (d) vs. ligation (12 trials, with 1309 patients). We
      used the risk difference (absolute risk reduction) as our main effect measure.
      RESULTS: The efficacy of acute sclerotherapy was highest vs. ligation at 95 %,
      with a small advantage for ligation (an overtube was used in eight trials) of 2.5
      % (95 % CI 0.4 % to 4.6 %) ( P = 0.018), but no survival difference. Efficacy of
      sclerotherapy combined with vasoconstrictors vs. vasoconstrictors alone was 86 %,
      whereas it was 83 % for sclerotherapy vs. vasoconstrictors alone. In both these
      groups sclerotherapy was superior for control of bleeding at, respectively, 16.3
      % (95 % CI 8.7 % to 23.9 % ( P = 0.0001) and 5.9 % (95 % CI, 1.5 % to 10.3 %) ( P
      = 0.008), with increased survival in the latter. In the combination group of
      sclerotherapy with vasoconstrictors, the efficacy of sclerotherapy alone was 69
      %, with the combination superior in controlling bleeding, at 13.2 % (95 % CI, 8.4
      % to 18.1 %) ( P < 0.0001) but with no survival difference. CONCLUSION: This
      comparison of sclerotherapy across trials demonstrates a problem in defining its
      real efficacy. The conclusive evidence for substituting banding ligation or the
      combination of vasoconstrictors with sclerotherapy as better therapeutic
      approaches has not been provided in randomized trials. Sclerotherapy can remain a
      gold standard in variceal bleeding but there is scope for further studies of
      ligation and vasoactive drugs.

PMID- 17001566
TI  - Conservative treatment versus endoscopic sphincterotomy in the initial management
      of acute cholecystitis in elderly patients at high surgical risk.
AB  - BACKGROUND AND STUDY AIMS: Surgery in elderly patients with acute cholecystitis
      is quite a high-risk procedure. The recent finding that activated pancreatic
      enzyme is present in sterile bile from the acutely inflamed gallbladder suggests
      that obstruction at the level of the common channel is a possible precipitating
      factor. It was therefore hypothesized that an initial endoscopic sphincterotomy
      in patients with acute cholecystitis might improve the clinical course. PATIENTS
      AND METHODS: A prospective unselected series of 105 patients over 65 years of age
      (52 men, 53 women; mean age 78) suffering from acute cholecystitis were initially
      treated on a random basis with either conservative methods or endoscopic
      sphincterotomy. Within the first 72 h after the onset of symptoms, all 52
      patients in the endoscopic sphincterotomy group were managed by endoscopic
      retrograde cholangiopancreatography (ERCP), combined with endoscopic
      sphincterotomy in 50 cases. The main study parameter was the need for emergency
      cholecystectomy within the first week after admission. RESULTS: Biliary sepsis
      requiring emergency surgery occurred in 15 patients in the conservatively treated
      group, in contrast with none of the 52 patients in the endoscopic sphincterotomy
      group ( P < 0.001). Iatrogenic complications after endoscopic sphincterotomy
      occurred in three patients, one of whom required surgery, while two were managed
      by conservative means. The clinical course improved, avoiding the need for
      emergency cholecystectomy and other interventions, in 48 patients in the
      endoscopic sphincterotomy group and in 36 patients in the conservatively treated
      group ( P < 0.01). CONCLUSIONS: The clinical course after endoscopic
      sphincterotomy improved in the majority of elderly patients suffering from acute
      cholecystitis, suggesting that early relief of obstruction at the level of the
      common channel reduces the risk of developing biliary sepsis. The majority of
      these patients can undergo surgery electively or can receive further conservative
      treatment.

PMID- 17001567
TI  - Two-stage treatment with preoperative endoscopic retrograde
      cholangiopancreatography (ERCP) compared with single-stage treatment with
      intraoperative ERCP for patients with symptomatic cholelithiasis with possible
      choledocholithiasis.
AB  - BACKGROUND AND STUDY AIMS: An ideal treatment for choledocholithiasis in the
      laparoscopic era has not been established. The objective of this study was to
      elucidate whether a treatment strategy of performing intraoperative endoscopic
      retrograde cholangiopancreatography (ERCP) during laparascopic cholecystectomy
      (when choledocholithiasis is confirmed by intraoperative cholangiography) is
      better for patients with suspected common bile duct stones than the current
      strategy (preoperative ERCP followed by laparoscopic cholecystectomy). PATIENTS
      AND METHODS: This was a prospective randomized study to evaluate which of these
      two approaches was most benefit- and cost-effective for patients with
      intermediate risk of choledocholithiasis. Patients underwent either preoperative
      ERCP followed by a laparoscopic cholecystectomy a few weeks later (the
      "preoperative ERCP" group) or intraoperative ERCP (the "intraoperative ERCP"
      group). Intraoperative ERCP was performed using the rendezvous technique.
      RESULTS: There were 64 patients in the preoperative ERCP group and 59 patients in
      the intraoperative ERCP group. The demographic and clinical characteristics of
      the two groups were similar, except that the bilirubin and gamma-glutamyl
      transferase (GGT) levels and the number of patients treated on an inpatient basis
      were higher in the preoperative ERCP group. Success rates were similar (96.6 % in
      the preoperative ERCP group vs. 90.2 % in the intraoperative ERCP group in the
      per-protocol study). Total morbidity, post-ERCP morbidity, and post-ERCP acute
      pancreatitis rates were higher in the preoperative ERCP group, but there were no
      differences between the two groups in the frequency of residual common bile duct
      stones, the conversion rate to open cholecystectomy, or surgical morbidity. The
      length of hospital stay and costs were lower in the intraoperative ERCP group
      despite the longer surgical times in this group. Univariate analysis did not find
      any relationship between morbidity and total bilirubin or GGT. Logistic
      regression analysis confirmed that morbidity was related only to the treatment
      group and the time spent in the operating room: the relative risk (RR) was 4.37
      for morbidity and 1.015 for the time spent in the operating room); the RR for
      papillotomy was 5.49. CONCLUSIONS: Both treatment approaches were equally
      effective but the intraoperative ERCP group had less morbidity, a shorter
      hospital stay, and reduced costs. The lower morbidity in the intraoperative ERCP
      group resulted from the lower rate of papillotomy and lower rates of post-ERCP
      pancreatitis and cholecystitis. Total morbidity was principally related to the
      type of treatment approach used.

PMID- 17001568
TI  - Similar performance but higher cholecystitis rate with covered biliary stents:
      results from a prospective multicenter evaluation.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic biliary stenting is now a well-established
      treatment method in patients with unresectable malignant biliary obstruction.
      Despite advances with metal stents, the problem of stent occlusion has not yet
      been resolved. Covered metal stents could reduce the occlusion rate by preventing
      tumor ingrowth, but have not been well evaluated. A prospective multicenter study
      was therefore conducted to evaluate the efficacy and disadvantages of covered
      Wallstents. PATIENTS AND METHODS: Covered Wallstents were implanted
      endoscopically in 62 patients with inoperable distal malignant biliary
      obstruction. Complications, stent patency, and patient survival were analyzed.
      RESULTS: Stent insertion was achieved in 61 of the 62 patients (98.4 %).
      Procedure-related complications were observed in four patients, consisting of
      minor pancreatitis (n = 2) and abdominal pain due to stent expansion (n = 2).
      There was no procedure-related mortality. Seven patients died too early for
      proper assessment, so that a total of 54 patients were ultimately evaluated.
      Stent dysfunction occurred in 17 of the 54 patients (31.5 %). The reasons for
      dysfunction were proximal tumor overgrowth (n = 5), migration (n = 3), lithiasis
      or food impaction (n = 3), cholangitis without the need for a repeat biliary
      intervention (n = 5), and unknown (n = 1). The median period of stent patency was
      142 days. No tumor ingrowth was observed. Acute cholecystitis was diagnosed in
      five patients (10 %) and was responsible for one death. Three stents were
      successfully removed. CONCLUSIONS: Covered biliary metal stents are effective for
      the drainage of distal malignant biliary obstruction, with a dysfunction rate
      apparently similar to that of uncovered stents. However, the risk of acute
      cholecystitis appears to be a major concern with this type of stent in patients
      with gallbladder in situ. Further comparative studies are needed.

PMID- 17001569
TI  - Troponin T after endoscopic retrograde cholangiopancreatography: no evidence of
      harm.
AB  - BACKGROUND AND STUDY AIMS: It is well recognized that myocardial ischemia can
      occur during endoscopic retrograde cholangiopancreatography (ERCP). Acute
      arrhythmias and ST segment changes have been reported by a number of authors, but
      the longer-term sequelae with regard to permanent myocardial damage are not
      known. The aim of this study was to determine the presence or absence of
      significant injury to the heart muscle. PATIENTS AND METHODS: Sixty-two patients
      undergoing therapeutic ERCP were assessed clinically and with electrocardiography
      (ECG) for the presence of ischemic heart disease before the procedure. Extensive
      intraprocedural monitoring was carried out, postprocedural ECGs were recorded,
      and serum troponin T levels were measured. The ECGs were evaluated blindly by a
      single cardiologist. RESULTS: In 61 of the 62 patients, no changes were observed
      between the ECGs before and after the procedure. One patient had postprocedural T
      wave inversion but a normal troponin T level, excluding myocardial damage. One
      patient with mild renal insufficiency and treated heart failure had borderline
      troponin T elevation (0.05 microg/l) but no ECG changes. No complications of ERCP
      occurred. CONCLUSIONS: Whilst ECG and rhythm changes indicating transient
      myocardial ischemia do occur during ERCP, there is no evidence that myocardial
      damage takes place as a consequence of this.

PMID- 17001570
TI  - Hemodynamic efficacy of the new resolution clip device in comparison with high
      volume injection therapy in spurting bleeding: a prospective experimental trial
      using the compactEASIE simulator.
AB  - BACKGROUND AND STUDY AIMS: Peptic ulcers are the most frequent cause of
      gastrointestinal bleeding. The use of hemoclips has become established as an
      effective form of treatment in addition to injection therapy. However, hemoclips
      have not previously been compared with injection therapy in an experimental
      setting using objective parameters. MATERIALS AND METHODS: In a prospective,
      randomized, and controlled trial, the disposable Resolution hemoclip device
      (Boston Scientific, n = 40) was compared with conventional injection therapy (n =
      40) in an experimental setting, using the compactEASIE simulator equipped with an
      upper gastrointestinal organ package to simulate bleeding. Four investigators
      with different levels of endoscopic experience participated in the study. On a
      randomized basis, each investigator treated 20 bleeding sites either by applying
      one clip (n = 10) or by carrying out high-volume four-quadrant injection (4 x 10
      ml saline) of a spurting vessel. The efficacy of the hemostasis was assessed by
      continuous measurement of pressure within the afferent vessel before and after
      clip application or injection therapy and calculating the relative reduction in
      the vessel's diameter with each treatment method. The system pressure was
      recorded 1 min before and 1 min after treatment. The ease of application of each
      method was rated by the endoscopist and by the assisting nurse using a visual
      analogue scale (0 - 100, with 100 being best). RESULTS: All of the 40
      hemoclipping and injection treatments were carried out successfully. Both methods
      led to a significant increase in peak pressure (Resolution clip 71.8 +/- 66.8 mm
      Hg, P < 0.001; injection 71.9 +/- 53.8 mm Hg, P < 0.001), representing a
      significant relative reduction in the vessel diameter. There were no significant
      differences in peak pressure between the two treatments ( P = 0.995). The mean
      increase in pressure during the first minute after the intervention (clip 49.3 +/
      67.0 mm Hg vs. injection 19.9 +/- 41.6 mm Hg) was significantly greater with the
      hemoclipping procedure ( P = 0.021). More experienced investigators achieved a
      greater increase in system pressure, but the difference was not significant. The
      assessments of the ease of application by the assistants (84 +/- 13) and
      endoscopists (86 +/- 16) did not show any significant differences ( P = 0.402)
      for the clipping device. CONCLUSIONS: No significant differences between the two
      treatment methods were detected with regard to the immediate efficacy of
      hemostasis. However, long-term hemostasis was better with hemoclipping. The
      endoscopist's level of experience also appears to play a role, particularly when
      hemoclips are used.

PMID- 17001572
TI  - A new method of diagnosing gastric intestinal metaplasia: narrow-band imaging
      with magnifying endoscopy.
AB  - BACKGROUND AND STUDY AIMS: With endoscopy, there is a high rate of interobserver
      variability in the identification of gastric intestinal metaplasia, and the
      endoscopic findings correlate poorly with the histological findings. Previous
      studies by our group investigating the use of a narrow-band imaging system with
      magnifying endoscopy (NBI-ME) in the gastric mucosa suggested that the appearance
      of a light blue crest (LBC) on the epithelial surface may be a distinctive
      endoscopic finding associated with the presence of intestinal metaplasia. The aim
      of the present study was to clarify the value of NBI-ME for diagnosing gastric
      intestinal metaplasia. PATIENTS AND METHODS: The LBC was defined as a fine, blue
      white line on the crests of the epithelial surface/gyri. To investigate the
      histology underlying the appearance of LBC, 44 biopsy specimens were obtained
      from regions containing LBC and 44 from non-LBC mucosa in 34 patients with
      atrophic gastritis. Three endoscopists then carried out NBI-ME in 107 consecutive
      patients to validate the diagnostic accuracy of the novel endoscopic technique.
      The degree of correlation between the LBC grading and the histological parameters
      of intestinal metaplasia was then assessed. RESULTS: The LBC grading correlated
      with cells that were positive for CD10 ( P = 0.0001) and Alcian blue ( P =
      0.036). The appearance of LBC correlated with histological evidence of intestinal
      metaplasia with a sensitivity of 89 % (95 % CI, 83 - 96 %), a specificity of 93 %
      (95 % CI, 88 - 97 %), a positive predictive value of 91 % (95 % CI, 85 - 96 %), a
      negative predictive value of 92 % (95 % CI, 87 - 97 %), and an accuracy of 91 %
      (95 % CI, 88 - 95 %). CONCLUSIONS: In narrow-band imaging with magnifying
      endoscopy, observation of a light blue crest on the epithelial surface in the
      gastric mucosa is a highly accurate sign of the presence of histological
      intestinal metaplasia.

PMID- 17001571
TI  - Nonendoscopic transnasal placement of a wireless capsule for esophageal pH
      monitoring: feasibility, safety, and efficacy of a manometry-guided procedure.
AB  - BACKGROUND AND STUDY AIMS: The aim of the study was to evaluate the safety,
      feasibility, and efficacy of transnasal placement of the Medtronic Bravo capsule
      for wireless esophageal pH monitoring. PATIENTS AND METHODS: Forty patients with
      symptomatic gastroesophageal reflux disease were prospectively evaluated. All
      patients underwent upper gastrointestinal endoscopy and esophageal manometry. The
      Bravo capsule was then introduced transnasally and released 5 cm above the upper
      margin of the lower esophageal sphincter. Serial radiographs were performed
      weekly until capsule release. RESULTS: Of the 40 patients who were evaluated, 38
      (95 %) were eligible to undergo the procedure. Transnasal placement proved
      impossible in one patient (2.5 %). Overall, a total of 39 procedures were
      performed in 38 patients (the procedure was repeated in one patient because of
      accidental intragastric fixation). Esophageal placement was successful in 36/39
      procedures (92.3 %). The mean duration of the procedure was 10 minutes (range 5 -
      16 minutes). Adverse events were noted in five of the 39 procedures (12.8 %),
      mild epistaxis in two patients (5.1 %) and pharyngeal irritation in three
      patients (7.7 %). After the procedure, a slight "foreign body" sensation was
      reported by 20 of the 36 patients (55.5 %) who had undergone successful
      esophageal placement; two patients (5.5 %) experienced severe retrosternal pain
      necessitating endoscopic removal of the capsule. At the end of the study, 34 of
      the 38 patients (89.5 %) stated that they would be willing to undergo the test
      again if necessary. CONCLUSIONS: Transnasal placement of the Bravo pH capsule is
      safe, well tolerated, does not require sedation, and avoids endoscopy and its
      complications.

PMID- 17001573
TI  - Potential impact of EUS-FNA staging of proximal lymph nodes in patients with
      distal esophageal carcinoma.
AB  - BACKGROUND AND STUDY AIMS: Distal esophageal carcinomas can be resected using
      transthoracic esophagectomy or transhiatal esophagectomy. Accurate diagnosis of
      subcarinal and supracarinal lymph-node metastases is important for selecting the
      surgical strategy. The impact of endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA) on the preoperative diagnosis of subcarinal and supracarinal
      lymph-node metastases in patients with distal esophageal carcinoma was therefore
      investigated. PATIENTS AND METHODS: Patients with a resectable distal esophageal
      carcinoma and subcarinal and/or supracarinal lymph nodes visualized on
      preoperative EUS were prospectively included. The lymph nodes were sampled using
      EUS-FNA, and if they were found to have metastases, transthoracic resection was
      offered; by contrast, patients without metastases were offered a transhiatal
      resection. RESULTS: Lymph-node metastases were found with EUS-FNA in 11 of the 48
      patients included (23 %). Thirteen patients had suspicious nodes on EUS, in four
      of whom (31 %) the diagnosis was changed into nonmalignant nodes with FNA. Thirty
      five patients had nonsuspicious nodes on EUS, in three of whom (9 %) the FNA
      procedure revealed malignant cells. CONCLUSIONS: EUS with the addition of the FNA
      procedure has a significant impact on decision-making in patients with esophageal
      carcinoma in whom transhiatal esophagectomy would otherwise be planned.

PMID- 17001574
TI  - Clinical relevance of colonic lesions in cirrhotic patients with portal
      hypertension.
AB  - BACKGROUND AND STUDY AIMS: This prospective study was conducted in order to
      evaluate whether the colonic lesions previously described in cirrhotic patients
      may be of clinical relevance. PATIENTS AND METHODS: Eighty-five patients with
      cirrhosis of the liver, but without colonic or systemic diseases unrelated to the
      liver disease, underwent colonoscopy and were followed up for at least 2 years.
      RESULTS: Colonic varices were observed in 31 % of the patients, portal
      hypertensive colopathy (PHC; defined as diffuse hyperemia, edema, spider
      angiomas, and spontaneous bleeding of the colonic mucosa) in 54 %, and normal
      colonic findings in 18 %. Colonic varices and PHC were present simultaneously in
      27 % of the patients. Previous sclerotherapy or band ligation treatment for
      esophageal varices had been carried out in 27 % and 23 % of the patients,
      respectively. Portal hypertensive gastropathy was observed in 42 % of the
      patients. Polyps were found in 12 % of the cirrhotic patients and cancer in 3 %.
      All of the patients were followed up for at least 2 years; 34 % of them developed
      upper gastrointestinal hemorrhage (81 % from esophageal varices, 19 % from the
      stomach), while only 6 % developed lower gastrointestinal bleeding. CONCLUSIONS:
      Colonic lesions are frequent in cirrhotic patients, but statistical analysis
      showed that these lesions are not specific for the disease and do not correlate
      with the etiology and degree of cirrhosis, with the endoscopic treatment of
      esophageal varices, or with the risk of bleeding from the lower gastrointestinal
      tract.

PMID- 17001575
TI  - The role of simeticone in small-bowel preparation for capsule endoscopy.
AB  - BACKGROUND AND STUDY AIMS: Capsule endoscopy is a new diagnostic method allowing
      painless visualization of the entire small bowel. However, there is as yet no
      standardized protocol for bowel preparation before the examination. The aim of
      this study was to assess the effectiveness of simeticone in reducing bowel gas
      bubbles in patients undergoing capsule endoscopy. PATIENTS AND METHODS: A
      randomized, prospective, and controlled study was conducted, including 56
      patients, from March to October 2004. The patients were randomly allocated to
      groups receiving either simeticone or no simeticone, on the basis of a computer
      generated random number table. Patients in the simeticone group (n = 28) received
      300 mg simeticone for bowel preparation 20 min before capsule endoscopy, while
      patients in the non-simeticone group (n = 28) received no medication for bowel
      preparation. Two experienced endoscopists assessed and graded the visibility of
      the mucosa and intraluminal gas bubbles in a single-blinded fashion. RESULTS: The
      visibility of the mucosa in the proximal small bowel in patients who received
      preparation with simeticone was considered to be better, with fewer intraluminal
      bubbles, than in those without bowel preparation ( P < 0.025). Interobserver
      agreement was excellent ( R > or = 0.8, P < 0.05). No adverse effects of
      simeticone were observed. CONCLUSIONS: Simeticone administration before capsule
      endoscopy improves the visualization of the mucosa in the proximal small
      intestine.

PMID- 17001576
TI  - Autologous fibrin sealant (Vivostat) for mesh fixation in laparoscopic
      transabdominal preperitoneal hernia repair.
AB  - BACKGROUND AND STUDY AIMS: The use of fibrin glue derived from humans or animals
      has been reported as an alternative method of mesh fixation, instead of staples,
      in inguinal hernia repair. However, fibrin sealants involve the potential risks
      of virus transmission or immunological reactions to foreign proteins. This risk
      could be avoided by using autologous fibrin derived from the patient. A
      feasibility study on the use of autologous fibrin was therefore carried out in
      patients undergoing laparoscopic transabdominal inguinal hernia repair. PATIENTS
      AND METHODS: In a series of 10 patients undergoing laparoscopic transabdominal
      inguinal hernia repair, autologous fibrin was produced from 120 ml of the
      patient's blood during the hernia repair. The process took an average of 20 min.
      The perioperative and postoperative results were compared with those in a control
      group of 20 patients in whom conventional fibrin was used. RESULTS: Producing and
      applying the autologous fibrin was uncomplicated. No differences in the outcome
      were observed between the two groups. One patient in the conventional fibrin
      group developed a seroma. None of the patients reported persistent pain. No
      recurrences were observed after a mean follow-up period of 9 months (range 6 - 12
      months) in the conventional fibrin group and 7 months (range 6 - 8 months) in the
      autologous fibrin group. CONCLUSIONS: This feasibility study suggests that
      autologous fibrin sealant allowed adequate mesh fixation that did not differ from
      that in a control group in whom conventional fibrin glue was used. Autologous
      fibrin may be an interesting alternative for a variety of laparoscopic and
      endoscopic applications.

PMID- 17001577
TI  - Treatment of hepatolithiasis by endoscopic chemoembolization of the left hepatic
      duct.

PMID- 17001580
TI  - Bowel preparation with oral sodium phosphate and renal disease.

PMID- 17001581
TI  - Post-insertion tailoring of plastic biliary stents: a novel technique.

PMID- 17001582
TI  - Endoscopic ultrasound-guided rescue of an uncovered self-expanding metallic stent
      causing biliary obstruction.

PMID- 17001583
TI  - Complication of endoscopic ultrasound-guided celiac plexus neurolysis.

PMID- 17001584
TI  - Successful endoscopic therapy of intrahepatic bile leaks following hepatic
      gunshot injury: report of two cases.

PMID- 17001585
TI  - Health status of older immigrants to Canada.
AB  - Using the 2000/2001 Canadian Community Health Survey (CCHS), this paper examines
      the health status of the older (aged immigrant population relative to that of non
      immigrants in order to identify areas where their health statuses diverge. First,
      we compare the health status of older immigrants (foreign-born) aged 55 and over
      in Canada to the Canadian-born in terms of age and gender using multiple measures
      of health status including self-assessed health. Second, we identify the factors
      associated with health status using the determinants of health framework. In both
      cases, the key questions are whether differences in health status exist and
      whether they are explained primarily by socio-economic, socio-demographic, or
      lifestyle factors that may point to problems with the Canadian health care
      system. Findings indicate that there is a relative comparability in the health
      status of older immigrants, even after controlling for age.

PMID- 17001586
TI  - Editorial: neglecting elders in the workplace: civil society organizations,
      ageism, and mandatory retirement.

PMID- 17001588
TI  - Relationship between self-report and performance measures of function: a
      systematic review.
AB  - The authors conducted a systematic review of studies examining correlations
      between assessments of function obtained using self-report and those obtained
      using performance-based measures for community-dwelling older adults. METHODS:
      Articles for this review were identified using electronic searching in MEDLINE,
      CINHAL, and AGELINE and hand-searching techniques. Two reviewers selected the
      studies that met the inclusion criteria, extracted the data, and assessed the
      methodological quality of the data. RESULTS: Seventeen studies met the inclusion
      criteria for review. Correlations between self-report and performance ranged from
      -0.72 to 0.60. Sixty per cent of the studies compared self-report instruments
      measuring disability with performance measures addressing functional limitations.
      In studies that assessed the same functional tasks and functional limitations
      using the two methods, the correlation varied between 0.60 and 0.86. CONCLUSION:
      When the construct measured by the two methods was the same, the correlations
      were moderate to large and, therefore, measurement of functional limitations by
      self-report or performance probably reflected a similar assessment of function.

PMID- 17001589
TI  - A literature review of randomized controlled trials of the organization of care
      at the end of life.
AB  - We searched nine electronic databases for randomized controlled trials (RCTs)
      about care at the end of life and found 23 RCTs. We assessed their quality using
      the criteria of the Cochrane Collaboration. The RCTs researched three themes: (a)
      the effect of providing palliative care through dedicated community teams on
      quality of life, on the management of symptoms, on satisfaction with care, on the
      duration of the palliative period, and on place of death; (b) the effects of
      specific palliative care interventions-advanced planning of care for the end of
      life, patient-held records, providing quality-of-life data to patients and
      physicians, grief education for relatives, palliative care education for nurses,
      and palliative care for patients with dementia; and (c) the costs of palliative
      compared to conventional care. We identify difficulties in conducting research on
      palliative care and solutions and discuss future possible research themes.

PMID- 17001590
TI  - Access to bathtub grab bars: evidence of a policy gap.
AB  - This paper examines access to bathtub grab bars in privately and publicly owned
      apartment buildings and explores the profile of seniors who have access to
      bathtub grab bars. Results indicate that bathtub grab bars were significantly
      more prevalent in apartments that were publicly owned (91.3%) as compared to
      privately owned (37.8%) (p < 0.05). Results of a logistic regression for
      participants residing in non-universal-access buildings indicated that seniors
      were more likely to have grab bars in their bathtubs if they were older, were in
      poor health, had had a fall in the previous year, or used a mobility aid. Among
      those who did not have bathtub grab bars, 33 per cent reported fear of falling
      while bathing, 20 per cent reported difficulty bathing, and 23 per cent were
      found to have impaired balance. Findings are discussed in light of policy
      implications for universal access to grab bars, with apartment buildings being a
      logical place to start.

PMID- 17001593
TI  - Abstracts of the 57th Annual Meeting of the American Association for the Study of
      Liver Diseases, October 27-31, 2006, Boston, Massachusetts, USA.

PMID- 17001591
TI  - Rural and urban Canadians with dementia: use of health care services.
AB  - The purpose of this research was to examine the characteristics of older
      Canadians with dementia (compared to those without dementia), their use of health
      care services, and the impact of place (rural/urban) on use of services. Andersen
      and Newman's Behavioural Model of Health Services Use (1973) guided the study. A
      cross-sectional design used data from the Canadian Community Health Survey (CCHS)
      Cycle 1.1 (N=49,995 older Canadians; those with dementia=313). Results indicated
      that among Canadian females between the ages of 50 and 64, those with dementia
      were more likely than those without dementia to live in rural areas. Among
      females 80 years of age and over, those with dementia had higher levels of
      education and income than those without dementia. In addition, a higher
      proportion of white than of visible minority Canadians was afflicted with
      dementia. The results further suggest that Canadians with dementia primarily
      required support services and that they were more likely than persons without
      dementia to report that their health care needs were unmet. It is recommended
      that publicly funded national home care programs be expanded to ensure that the
      supportive services needed by this population are available.

PMID- 17001595
TI  - Enamine-based aldol organocatalysis in water: are they really "all wet"?

PMID- 17001596
TI  - Single gold atoms in heterogeneous catalysis: selective 1,3-butadiene
      hydrogenation over Au/ZrO2.

PMID- 17001597
TI  - Rational design of bioorganometallic foldamers: a potential model for parallel
      beta-helical peptides.

PMID- 17001598
TI  - Stereoselective synthesis of superambrox: stereoselective type III intramolecular
      ene reaction and OH-assisted Ru-catalyzed isomerization.

PMID- 17001599
TI  - Massively parallel dip-pen nanolithography with 55 000-pen two-dimensional
      arrays.

PMID- 17001600
TI  - Characterization of bovine seminal plasma by proteomics.
AB  - Previous investigations of bovine seminal plasma (BSP) have revealed the
      identities of the three major proteins, BSP-PDC109, BSP-A3 and BSP-30 kDa, which
      together constitute about half of the total protein, as well as about 30 of the
      minor proteins. Analyses of BSP by 2-DE have revealed about 250 protein spots,
      suggesting that much of the BSP proteome remains undescribed. In this study, BSP
      has been analyzed by 2-D LC-based and SDS-PAGE-based proteomic methods. Ninety
      nine proteins were identified, including 49 minor proteins that have not
      previously been described in seminal plasma of any species.

PMID- 17001601
TI  - In vivo detection of secreted proteins from wounded skin using capillary
      ultrafiltration probes and mass spectrometric proteomics.
AB  - The identification of in vivo secreted proteins is a major challenge in systems
      biology. Here we report a novel technique using capillary ultrafiltration (CUF)
      probes to identify the secreted proteins involved in wound healing. CUF probes,
      which use semipermeable membrane hollow fibers to continuously capture secreted
      proteins, were used to sample skin wound fluids. To identify low-abundance
      proteins, we digested the CUF probe-collected wound fluid with trypsin and then
      directly subjected it to MS without using 2-DE separation. Two protein fragments
      with masses of 1565.7 and 1694.8 Da were identified by MS as peptides of thymosin
      beta10 and beta4, respectively. This is the first identification of thymosin
      beta10 as an in vivo constituent of the skin wound fluid. The LKKTETQ peptide, a
      common actin-binding domain of thymosin beta4 and beta10, significantly enhanced
      skin wound healing in vitro and in vivo. Our data suggest that the enhancement of
      wound healing by LKKTETQ may be mediated by purinergic receptors. The technique
      of using CUF probes linked to mass spectrometric proteomics represents a powerful
      method to identify in vivo secreted proteins, and may be applicable for
      identification of proteins relevant in various human diseases.

PMID- 17001602
TI  - Hypophosphorylation of the architectural chromatin protein DEK in death-receptor
      induced apoptosis revealed by the isotope coded protein label proteomic platform.
AB  - During apoptosis nuclear morphology changes dramatically due to alterations of
      chromatin architecture and cleavage of structural nuclear proteins. To
      characterize early events in apoptotic nuclear dismantling we have performed a
      proteomic study of apoptotic nuclei. To this end we have combined a cell-free
      apoptosis system with a proteomic platform based on the differential isotopic
      labeling of primary amines with N-nicotinoyloxy-succinimide. We exploited the
      ability of this system to produce nuclei arrested at different stages of
      apoptosis to analyze proteome alterations which occur prior to or at a low level
      of caspase activation. We show that the majority of proteins affected at the
      onset of apoptosis are involved in chromatin architecture and RNA metabolism.
      Among them is DEK, an architectural chromatin protein which is linked to
      autoimmune disorders. The proteomic analysis points to the occurrence of multiple
      PTMs in early apoptotic nuclei. This is confirmed by showing that the level of
      phosphorylation of DEK is decreased following apoptosis induction. These results
      suggest the unexpected existence of an early crosstalk between cytoplasm and
      nucleus during apoptosis. They further establish a previously unrecognized link
      between DEK and cell death, which will prove useful in the elucidation of the
      physiological function of this protein.

PMID- 17001603
TI  - Proteomic analysis of the E2F1 response in p53-negative cancer cells: new aspects
      in the regulation of cell survival and death.
AB  - E2F1 is an essential transcription factor that regulates cell-cycle progression
      and apoptosis. Overexpression of E2F1 sensitizes neoplastic cells to apoptosis
      and leads to tumor growth suppression, making it an interesting target for
      anticancer therapy. Use of E2F1 as a therapeutic, however, requires a detailed
      knowledge of the mechanisms by which it controls cellular proliferation and
      apoptosis, and of other potential E2F1 activities. In this study, a differential
      proteome analysis was performed to identify proteins associated with E2F1
      activity in inducible p53-deficient Saos-2ERE2F1 osteosarcoma cells. 2-DE
      revealed a distinct protein profile at 32 h after E2F1 activation. Thirty-three
      proteins were reproducibly identified as either up-regulated or down-regulated.
      Proteins were identified by MALDI-MS. They included hitherto unknown E2F1 target
      proteins of cytoskeletal origin, chaperones, enzymes, proteasomal proteins, and
      several heterogeneous nuclear ribonucleoproteins, suggesting its role in the ER
      stress response, protein degradation, and modulation of pre-mRNA splicing.
      Protein analysis-derived results were verified by Western blot using
      representative protein candidates. Thirteen identified proteins were the products
      of genes known to be cancer related. Thus, proteome analysis provides new
      information about the complexity of E2F1 activities in human cancer cells that
      may be considered when using E2F1 as a drug.

PMID- 17001604
TI  - Proteomic analysis of acute promyelocytic leukemia: PML-RARalpha leads to
      decreased phosphorylation of OP18 at serine 63.
AB  - In the present study, we employed 2-DE to characterize the effect of the acute
      promyelocytic leukemia (APL)-specific PML-RARalpha fusion protein on the
      proteome. Differentially expressed proteins, a number of which are related to the
      cell cycle function, including oncoprotein18 (OP18), heat shock protein70,
      glucose-regulated protein75, and peptidyl-prolyl isomerase, were identified by
      MS. Subsequent bioinformatic pathway discovery revealed an integrated network
      constituting SMARCB1, MYC, and TP53-regulated pathways. The data from the DNA
      microarray and proteomic experiments demonstrated the correlation between the
      translocation and higher expression of OP18 at mRNA and protein levels. Transient
      cotransfection assay revealed that PML-RARalpha is a potent activator of OP18
      promoter and this transcriptional activation is retinoic acid sensitive. PML
      RARalpha induction also leads to decreased phosphorylation on Ser63 residue of
      OP18, which is okadaic acid sensitive suggesting the involvement of a phosphatase
      pathway. Overexpression of a constitutively phosphorylated Ser63 mutant of OP18
      in PML-RARalpha expressing APL patient, PR9, and NB4 cells led to a G2/M-phase
      arrest in contrast to a phosphorylation-deficient Ser63 mutant and untransfected
      control. Taken together, our results demonstrate the significance of decreased
      Ser63 phosphorylation of OP18 in PML-RARalpha-mediated effects on cell cycle.

PMID- 17001605
TI  - Proteomics for the analysis of the Candida albicans biofilm lifestyle.
AB  - Candida albicans is an opportunistic pathogenic fungus capable of causing
      infections in immunocompromised patients. Candidiasis is often associated with
      the formation of biofilms on the surface of inert or biological materials.
      Biofilms are structured microbial communities attached to a surface and encased
      within a matrix of exopolymeric substance (EPS). At present, very little is known
      about the changes in protein profiles that occur during the transition from the
      planktonic to the biofilm mode of growth. Here, we report the use of proteomics
      for the comparative analysis of subcellular fractions obtained from C. albicans
      biofilm and planktonic cultures, including cell surface-associated proteins and
      secreted components present in liquid culture supernatants (for planktonic
      cultures) and EPS (for biofilms). The analysis revealed a high degree of
      similarity between the protein profiles associated with the planktonic and
      biofilm extracts, and led to the identification of several differentially
      expressed protein spots. Among the differentially expressed proteins, there was a
      preponderance of metabolic enzymes that have been described as cell surface
      proteins and immunodominant antigens. Proteins found in the biofilm matrix
      included a few predicted to form part of the secretome, and also many secretion
      signal-less proteins. These observations contribute to our understanding of the
      C. albicans biofilm lifestyle.

PMID- 17001607
TI  - Oxygen status of lung granulomas in Mycobacterium tuberculosis-infected mice.
AB  - It is often assumed that Mycobacterium tuberculosis (Mtb)-induced granulomatous
      lesions, particularly those undergoing central caseation, are anoxic, and that
      the survival of Mtb in these lesions requires the integrity of its non-oxidative
      respiratory pathways. Using the hypoxia marker pimonidazole, we now provide
      immunohistochemical evidence that in the most frequently used animal model system
      of inbred mice Mtb-induced granulomas, even after more than one year of aerogenic
      infection, are not severely hypoxic. In contrast, chronic aerosol infection with
      M. avium strain TMC724 was associated with hypoxia surrounding necrotizing
      granuloma centres. Direct measurements of oxygen tension with a flexible
      microelectrode in mouse lungs chronically infected with Mtb disclosed a wide
      range of oxygen partial pressures in different parts of the lungs which, however,
      rarely approached the anoxic conditions consistently found in necrotizing
      tumours. We further show that an Mtb mutant, defective in nitrate reductase
      (narG) necessary for survival under anaerobic conditions in vitro, can persist in
      the lungs of chronically infected mice to a similar extent as wild-type Mtb.
      These findings have important implications for the use of the mouse model of Mtb
      infection in developing eradication chemotherapy and for evaluating putative
      mechanisms of chronic persistence and latency of Mtb.

PMID- 17001608
TI  - Synthesis of a functional C2-symmetrical bidentate diphenylphosphonite DIOP
      derivative and its conversion into the corresponding pi-acidic
      bis(pentafluorophenyl) and bis(p-tetrafluoropyridyl) compounds.
AB  - The reaction of a C2-symmetric diiodo compound, 1,4-dideoxy-1,4-diiodo-2,3,-O
      isopropyliden-L-threitole, with [K([18]crown-6)]P(CN)2 led to the generation of a
      corresponding bidentate dicyanophosphorus derivative. The in situ reaction with
      excess methanol and phenol yielded the corresponding bidentate dimethyl- and
      diphenylphosphonites, respectively. The isolated liquids were characterized by
      multinuclear NMR spectroscopy, elemental analysis, and mass spectrometry. The
      bidentate diphenylphosphonite ligand (a diphenoxyphosphane derivative) represents
      one of the very few functional bidentate phosphane derivatives: a DIOP [(2,2
      dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene)]bis(diphenylphosphane)
      modification, in which the phenyl groups at the phosphorus atoms are replaced by
      functional phenoxy groups. Treatment of the bidentate diphenylphosphonite
      derivative with C6F5MgBr and p-C5NF4MgBr allowed the isolation and full
      characterization of the comparable bidentate bis(pentafluorophenyl) and bis(p
      tetrafluoropyridyl)phosphanes. The ligand properties of the novel bidentate
      ligand systems were evaluated through the synthesis and vibrational investigation
      of their tetracarbonyl-molybdenum and cyclopentadienyl-iron complexes. The pi
      acidity of the synthesized ligands increases in the order methoxy-<phenoxy
      <pentafluorophenyl-<p-tetrafluoropyridyl phosphane.

PMID- 17001609
TI  - Syntheses, structures, and anion-binding properties of two novel
      calix[2]benzo[4]pyrroles.
AB  - Calix[2]benzo[4]pyrrole m-6 and p-6, each containing two dipyrromethane moieties
      and two m-phenylene or p-phenylene units, respectively, were readily synthesised
      from pyrrole, 1,3- and 1,4-bis(1,1'-dimethylhydroxymethyl)benzene, (m-4 and p-4,
      respectively) and acetone. Macrocycles m-6 and p-6 were tested as receptors for a
      selection of anions, such as acetate, dihydrogenphosphate and fluoride. The X-ray
      structures of m-6 and p-6 and those of the complexes m-6F(-), m-6Cl(-) and m
      6CH(3)COO(-) (with an nBu(4)N(+) counterion) were also determined.

PMID- 17001610
TI  - Anion-binding properties of the tripyrrolemethane group: a combined experimental
      and theoretical study.
AB  - Tripyrrolemethane- and bistripyrrolemethane-containing systems were recently
      reported to be efficient and selective hosts for anions. Nevertheless, the basic
      intrinsic properties of tripyrrolemethane as a ligand for anions have not yet
      been explored. Here we report the study of the anion-binding properties of the
      tripyrrolemethane group. We applied a combined experimental and theoretical
      approach to determine the affinity of the tripyrrolemethane system for different
      anions in the gas phase, in solution and in the crystalline state. In the
      crystal, the tripyrrolemethane group forms a number of different complexes with
      the bromide ion, some involving the participation of more than one ligand
      species. Despite the very similar basicity of fluoride and dihydrogen phosphate,
      the tripyrrolemethane ligand exhibits a clear preference for the fluoride anion
      in solution, which indicates an anion-binding system and not merely
      deprotonation. Although the affinity of the tripyrrolemethane ligand for other
      ions was negligible in solution, gas-phase studies show that complexation with
      larger halide ions is favoured over complexation with fluoride.

PMID- 17001611
TI  - Enantioselective palladium-catalyzed total synthesis of vitamin e by employing a
      domino Wacker-Heck reaction.
AB  - An enantioselective total synthesis of vitamin E in which a novel palladium
      catalyzed domino reaction was employed as the key step is described. This
      reaction allows the formation of the chiral chroman framework and the concurrent
      introduction of part of the side chain of vitamin E. The sequence comprises an
      enantioselective Wacker cyclization and a subsequent Heck reaction. Accordingly,
      reaction of alkenylphenol 12 with methyl vinyl ketone (13) in the presence of
      catalytic amounts of Pd(OTFA)(2) (TFA = trifluoroacetate), the enantiopure ligand
      (S,S)-Bn-BOXAX (8 b; Bn = benzyl, BOXAX = 2,2'-bis(oxazolyl)-1,1'-binaphthyl, and
      p-benzoquinone (9) as an oxidant gives access to chiral chroman 10 with an
      enantioselectivity of 97 % ee in 84 % yield. Chroman 10 is then converted into 24
      by an aldol condensation reaction with (3R)-3,7-dimethyloctanal (11). Subsequent
      1,2-addition of methyllithium, elimination of water, and hydrogenation yields
      vitamin E.

PMID- 17001612
TI  - Diacetyldiamidoximeester of pentamidine, a prodrug for treatment of protozoal
      diseases: synthesis, in vitro and in vivo biotransformation.
AB  - Pentamidine is an effective antimicrobial agent. To increase its poor oral
      bioavailability due to the strong basic amidine functionality, the less basic O
      acetylamidoxime prodrug, the diacetyldiamidoximeester, was used, which has
      greatly improved lipophilicity. The objectives of this investigation were the
      synthesis of all potential metabolites of the double prodrug, the conformational
      analysis of its structure, and to study the in vitro and in vivo
      biotransformation by ester cleavage and N-reduction to pentamidine via four
      intermediate metabolites. The biotransformation of diacetyldiamidoximeester to
      pentamidine involving the reduction of the amidoxime function and the ester
      cleavage could be demonstrated. The kinetic parameters were determined.
      Amidoximes were efficiently metabolized by several enzyme systems located in
      microsomes and mitochondria of different organs including the final formation of
      the active metabolite pentamidine. The formation of pentamidine after oral
      administration of the diacetyldiamidoximeester to rats could be demonstrated as
      well.

PMID- 17001613
TI  - Monitoring the ligand binding mode by proton NMR chemical shift differences.

PMID- 17001614
TI  - Granulatoside A, a starfish steroid glycoside, enhances PC12 cell neuritogenesis
      induced by nerve growth factor through an activation of MAP kinase.

PMID- 17001615
TI  - Cell surface characterization of Yarrowia lipolytica IMUFRJ 50682.
AB  - In the present work, the surface characteristics of a wild-type strain of
      Yarrowia lipolytica (IMUFRJ50682) were investigated. Six different methods to
      characterize cell surfaces--adhesion to polystyrene; hydrophobic interaction
      chromatography (HIC); microbial adhesion to solvents (MATS) test; zeta potential;
      microbial adhesion to hydrocarbons (MATH) test; and contact angle measurement
      (CAM)--were employed to explain the cell surface behaviour of Y. lipolytica
      (IMUFRJ50682). This Y. lipolytica strain presents significant differences at the
      cell surface compared with another Y. lipolytica strain (W29) previously reported
      in the literature. The main difference is related to the higher cell adhesion to
      non-polar solvents. The proteins present on the cell wall of Y. lipolytica
      IMUFRJ50682 seem to play an important role in these particular surface
      characteristics because of the consistent reduction of this yeast hydrophobic
      character after the action of pronase on its cell wall.

PMID- 17001616
TI  - Application of PCR-DGGE to analyse the yeast population dynamics in slurry
      reactors during degradation of polycyclic aromatic hydrocarbons in weathered oil.
AB  - Slurry-phase reactors have been used to investigate the biodegradation
      feasibility of polycyclic aromatic hydrocarbons (PAHs) in weathered crude oil, by
      mixed culture containing five PAHs-degrading yeast strains. Yeasts were isolated
      from the oily soil by enrichment culture, using phenanthrene as a sole carbon
      source, and identified based on the 26S ribosomal DNA (rDNA) sequence. Yeast
      strains belonged to the genera Candida, Pichia, Rhodotorula and Sporidiobolus.
      The experiment was carried out for a period of 6 weeks at room temperature with a
      solid : liquid ratio of 50% w/w. The results showed that high removal efficiency
      was obtained for all PAHs, including low molecular weight (LMW) and high
      molecular weight (HMW) compounds (89.3-98.6% and 66.3-89.4% within 6 weeks,
      respectively). The higher removal efficiency for HMW-PAHs obtained in this work
      suggested that yeast strains mixture could play an important role to reclaim oil
      contaminated sites. Denaturing gradient gel electrophoresis (DGGE) of polymerase
      chain reaction (PCR)-amplified 26S rRNA genes was used to follow the changes of
      yeast populations during the slurry reactor process. The results of DGGE
      indicated that Candida maltosa-like and Pichia guilliermondii were the dominant
      species but Rhodotorula dairenensis appeared as a weak band and Sporidiobolus
      salmonicolor and Pichia anomala disappeared during the study. Moreover, the
      results showed that all of the five strains, including the two belonging to the
      same genus, could be differentiated from each other in the DGGE profile.

PMID- 17001618
TI  - Combined use of two transcriptional reporters improves signalling assays for G
      protein-coupled receptors in fission yeast.
AB  - The biochemical and genetic tractability of yeasts make them ideal hosts for the
      analysis of signalling from G protein-coupled receptors (GPCRs). Selected
      modifications to the strains allow the introduction of non-yeast components,
      while signal-dependent expression of reporter genes provides growth selection or
      enzyme read-out as assays for signalling. One issue with such systems is reporter
      expression in the absence of stimulation, usually because of spontaneous
      activation of intracellular signalling components and/or incomplete repression of
      the signal-dependent promoter. This limits the difference between reporter
      activity in the presence and absence of stimulation, often referred to as the
      signal:background ratio. In an effort to extend the applicability of the yeast
      system, we generated a Schizosaccharomyces pombe strain containing pheromone
      dependent reporters for both growth selection and beta-galactosidase production.
      Simultaneous use of the two reporters provided several advantages over strains
      expressing only one reporter, particularly when coupled to the use of a
      competitive inhibitor of the nutritional reporter. For example, the beta
      galactosidase signal:background ratio following stimulation with 10(-6) M P
      factor increased from 35 for a strain containing a single lacZ reporter to almost
      2500 for the double reporter. The sensitivity of the system was also improved,
      with higher signal:background ratios allowing detection of lower concentrations
      of P-factor. Although we have used Sz. pombe and focused on GPCR-based induction
      of beta-galactosidase, the principles described can be applied to other yeasts,
      different signalling pathways and alternative reporters.

PMID- 17001619
TI  - Acute insulin response is an independent predictor of type 2 diabetes mellitus in
      individuals with both normal fasting and 2-h plasma glucose concentrations.
AB  - BACKGROUND: Earlier prospective studies have identified insulin action and
      secretion as predictors of T2DM in populations with normal glucose tolerance
      (NGT) and impaired glucose tolerance (IGT) (2-h OGTT < 7.8 and 7.8-11 mmol/L,
      respectively). Fasting plasma glucose (FPG), an additional and recently modified
      (normal <5.6 mmol/L) diagnostic criterion is associated with insulin secretion.
      We wanted to establish whether insulin secretion persists as an independent
      predictor of T2DM in individuals with no clinical evidence of impaired glucose
      regulation based on FPG and 2-h plasma glucose concentrations. METHODS: Insulin
      action (M, euglycemic-hyperinsulinemic clamp), insulin secretion (acute insulin
      response (AIR), IVGTT), and adiposity (%Fat, DXA or densitometry) were compared
      at baseline in 358 Pima Indians (232M/126F, 18-44 years old) with normal glucose
      regulation of whom 61 (35M/26F) developed diabetes (DIAB) during a median follow
      up time of 7.6 years. RESULTS: In proportional-hazard analysis, % Fat (HR = 1.52,
      p = 0.03), M (HR = 0.51, p = 0.04) and AIR (HR = 0.64, p = 0.003) predicted the
      development of diabetes after adjustment for age and sex. In regression analysis
      adjusting for age, sex, %Fat and M at baseline, the non-diabetic group (NON-DM)
      had a higher AIR (p = 0.0002) than the DIAB group; the positive association of
      AIR with adiposity observed in the NON-DM group was absent in the DIAB group.
      Cumulative incidence rates (12y) for diabetes were highest (48%) in subjects with
      both M and AIR below the population median and lowest (11%) in subjects with both
      M and AIR above the population median. CONCLUSION: AIR can predict diabetes prior
      to the current clinical indicators of impaired glucose regulation.

PMID- 17001621
TI  - A novel type of deletion in the CDKN2A gene identified in a melanoma-prone
      family.
AB  - Linkage to the CDKN2A locus has been demonstrated in approximately 50% of
      families with hereditary malignant melanoma but only a subgroup of these harbor
      identified mutations. We here report a Norwegian melanoma-prone family with a
      novel large germline deletion removing 13707 bps of the CDKN2A gene, including
      exon 1alpha and approximately half of exon 2. Our finding is the first reported
      large CDKN2A germline deletion with a breakpoint located within an exon. This
      type of deletion is not detectable through the direct exon sequencing and may
      also escape identification by use of multiplex ligation-dependent probe
      amplification (MLPA) analysis. Here, the defect was identified through detection
      of a truncated p14(ARF) mRNA and loss of p16(INK4a) mRNA expression from the
      affected allele. Our finding suggests that atypical, large deletions in the
      CDKN2A gene may explain linkage to the 9p21 chromosome band without identified
      gene mutations among melanoma-prone families. Thus, it illustrates the need to
      include p14(ARF)- and p16(INK4a) transcript analysis when searching for unknown
      mutations within the CDKN2A locus in melanoma-prone families. Similar deletions
      with atypical breakpoints may affect other genes involved in cancer disposition,
      and the need to examine gene transcripts in high-risk families with no mutation
      identified through conventional testing should be considered.

PMID- 17001622
TI  - Characterization of the breast cancer associated ATM 7271T>G (V2424G) mutation by
      gene expression profiling.
AB  - Mutations in ATM are responsible for the autosomal recessive disorder ataxia
      telangiectasia. Heterozygous mutations in ATM have been associated with an
      elevated risk of breast cancer. We previously reported one breast cancer family
      in which ATM 7271T>G (V2424G) segregated with disease, and apparently acted in a
      dominant negative manner. We now report the screening of 782 multiple-case breast
      cancer families that identified two additional index cases with ATM 7271T>G.
      Phylogenetic sequence analysis showed that V2424 is a highly conserved residue,
      and that the 2424G variant is likely to interfere with function. To elucidate the
      consequences of this mutation, we expression profiled wild-type, heterozygous,
      and homozygous lymphoblastoid cell lines (LCLs) from Scottish and Australian
      families using an oligonucleotide microarray. Cluster analysis revealed 77 genes
      that were differentially expressed in homozygous and heterozygous V2424G cells
      (compared to wild-type) and 11 genes differentially expressed in the homozygous
      cells. We also evaluated the profiles of LCLs after exposure to ionizing
      radiation (IR) and identified 77 genes that were differentially expressed in wild
      type cells, but not in homozygous or heterozygous V2424G cells. We validated the
      expression differences by RT-PCR in additional heterozygous V2424G LCLs from
      another breast cancer family. We found no consistent cytotoxicity or abrogation
      of ATM kinase activity after IR in seven heterozygous V2424G LCLs, compared to
      wild-type LCLs, but did find an increase in the number of chromosomal
      aberrations. These data suggest that the V2424G missense mutation acts largely as
      a dominant negative in terms of the associated expression profiles.

PMID- 17001623
TI  - Impact of trisomy 8 on expression of genes located on chromosome 8 in different
      AML subgroups.
AB  - Trisomy 8 is the most frequently observed trisomy in acute myeloid leukemia (AML)
      occurring as a sole karyotype abnormality or in addition to other chromosome
      aberrations. It was the aim of this study to analyze the impact of trisomy 8 on
      the expression of genes located on chromosome 8 in distinct AML subgroups
      characterized by different chromosome abnormalities in addition to trisomy 8.
      Gene expression analyses were performed on a total of 567 AML cases comprising
      the following subgroups: +8 sole, +8 within a complex aberrant karyotype, +8 in
      addition to t(15;17), inv(16), t(8;21), 11q23/MLL, or other abnormalities, AML
      with normal karyotype and the before mentioned subgroups without trisomy 8. A
      significant higher mean expression of genes located on chromosome 8 was observed
      in subgroups with +8 in comparison to their respective control groups. A varying
      number of significantly higher expressed genes was identified in all comparisons.
      No gene was significantly overexpressed in all comparisons, and no distinct gene
      expression pattern was identified allowing the identification of cases with
      trisomy 8. In conclusion, the gain of chromosome 8 leads to a higher expression
      of genes located on chromosome 8. However, no consistent pattern of genes was
      identified, which shows a higher expression in all AML subtypes with trisomy 8.
      These data suggest that trisomy 8 rather provides a platform for a higher
      expression of chromosome 8 genes which are individually up-regulated by the
      respective primary genetic abnormalities. Therefore, trisomy 8 in AML determines
      no specific disease characteristic but is a disease modulating secondary event.

PMID- 17001624
TI  - Optimization of ethanol production from starch by an amylolytic nuclear petite
      Saccharomyces cerevisiae strain.
AB  - Ethanol fermentation characteristics of the 100% respiratory-deficient nuclear
      petite amylolytic Saccharomyces cerevisiae NPB-G strain was investigated in both
      shake-flask and controlled bioreactor cultivation conditions, and comparison with
      the earlier reported results revealed 54.6% increase in ethanol yield. Efforts to
      improve the starch utilization rate by increasing the selection pressure or
      supplying the fermentation medium with glucose did not prevent the observed
      decrease in time-dependent amylolytic activity. Response surface methodology
      (RSM) was then used as a statistical tool to optimize the initial yeast extract
      and starch contents of the medium, which resulted in a substantial increase in
      the stability of the expression plasmid in both the respiratory-deficient NPB-G
      and the parental respiratory-sufficient WTPB-G strains, with concomitant
      improvement in their amylolytic potentials. High ethanol yields on substrate
      values of the bioreactor cultures, which were very close to the theoretical
      yield, indicated that the amylolytic respiratory-deficient NPB-G strain was
      effective in the direct fermentation of starch into ethanol.

PMID- 17001625
TI  - Is it going to be SIN?: a European Society of Gene Therapy commentary. Phasing
      out the clinical use of non self-inactivating murine leukemia virus vectors:
      initiative on hold.
AB  - Insertional mutagenesis resulting in a leukaemia-like lymphoproliferative
      disease, as observed in the X-SCID (severe combined immunodeficiency) clinical
      trial using a gamma-retroviral vector that transferred a functional copy of the
      defective gene into hematopoietic precursor cells of affected children, sparked a
      debate about a ban on conventional gamma-retroviral vectors. This commentary
      summarizes the relevant data on this topic and concludes that there is no
      preclinical or clinical evidence as yet that SIN vectors, which self-inactivate
      the retroviral long terminal repeats (LTRs), will indeed show an improved safety
      profile. Conventional murine leukaemia virus (MLV) vectors can thus be used
      further in clinical gene therapy trials but require a thorough case-by-case risk
      benefit analysis.

PMID- 17001626
TI  - The Journal of Gene Medicine European Society of Gene Therapy Young Investigator
      Award 2006.

PMID- 17001627
TI  - Symptom severity and lifetime and prospective health service use among military
      veterans evaluated for PTSD.
AB  - We used structural equation modeling with 174 treatment-seeking military trauma
      survivors evaluated for posttraumatic stress disorder (PTSD) at a VA Medical
      Center PTSD clinic to examine relationships among lifetime mental health service
      use, PTSD symptom severity and medical problems (from self-report), as well as
      prospective (1-year) mental health and medical care use visit counts extracted
      from medical records. We discovered an adequate statistical fit to a hypothesized
      model of previous and prospective health service use, and current PTSD severity
      and health-related problems. Previous inpatient mental health treatment was
      significantly related to PTSD severity and prospective outpatient mental health
      use. However, PTSD severity was unrelated to prospective use of mental health or
      medical services. Health problems were related to prospective medical service
      use. Clinical and administrative implications in predicting health care use among
      trauma survivors are discussed.

PMID- 17001628
TI  - Demographic and clinical characteristics of motor vehicle accident victims in the
      community general health outpatient clinic: a comparison of PTSD and non-PTSD
      subjects.
AB  - Motor vehicle accidents (MVAs) are the leading cause of posttraumatic stress
      disorder (PTSD) in the general population, often with enduring symptomatology.
      This study details epidemiological and clinical features that characterize PTSD
      among MVA victims living in a nonhospitalized community setting long after the
      MVA event, and includes exploration of premorbid and peritraumatic factors. MVA
      victims (n=60; 23 males, 37 females) identified from the registry of a community
      general health outpatient clinic during a 7-year period were administered an
      extensive structured battery of epidemiological, diagnostic and clinical ratings.
      Results indicated that 30 subjects (50%; 12 males, 18 females) had MVA-related
      PTSD (MVAR-PTSD). Among those with PTSD, 16 individuals exhibited PTSD in partial
      remission, and six, in full remission. There were no significant demographic or
      occupational function differences between PTSD and non-PTSD groups. The most
      common comorbid conditions with MVAR-PTSD were social phobia (20%), generalized
      anxiety disorder (7.8%) and obsessive-compulsive disorder (0.5%). Previous MVA's
      were not predictive of PTSD. Subjects with MVAR-PTSD scored worse on the
      Clinician-Administered Posttraumatic Stress Disorder Scale, Part 2 (CAPS-2),
      Impact of Event Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating
      Scale, Impulsivity Scale, and Toronto Alexithymia Rating Scale. Study
      observations indicate a relatively high rate of PTSD following an MVA in a
      community-based sample. The relatively high rate of partially remitted MVAR-PTSD
      (N=16) underscores the importance of subsyndromal forms of illness. Alexithymia
      may be an adaptive method of coping with event stress. The development of PTSD
      appears not to be associated with the severity of MVA-related physical injury.

PMID- 17001629
TI  - Saccharomyces cerevisiae S288C genome annotation: a working hypothesis.
AB  - The S. cerevisiae genome is the most well-characterized eukaryotic genome and one
      of the simplest in terms of identifying open reading frames (ORFs), yet its
      primary annotation has been updated continually in the decade since its initial
      release in 1996 (Goffeau et al., 1996). The Saccharomyces Genome Database (SGD;
      www.yeastgenome.org) (Hirschman et al., 2006), the community-designated
      repository for this reference genome, strives to ensure that the S. cerevisiae
      annotation is as accurate and useful as possible. At SGD, the S. cerevisiae
      genome sequence and annotation are treated as a working hypothesis, which must be
      repeatedly tested and refined. In this paper, in celebration of the tenth
      anniversary of the completion of the S. cerevisiae genome sequence, we discuss
      the ways in which the S. cerevisiae sequence and annotation have changed,
      consider the multiple sources of experimental and comparative data on which these
      changes are based, and describe our methods for evaluating, incorporating and
      documenting these new data.

PMID- 17001630
TI  - Alginate microparticles as novel carrier for oral insulin delivery.
AB  - Alginate microparticles produced by emulsification/internal gelation were
      investigated as a promising carrier for insulin delivery. The procedure involves
      the dispersion of alginate solution containing insulin protein, into a water
      immiscible phase. Gelation is triggered in situ by instantaneous release of ionic
      calcium from carbonate complex via gentle pH adjustment. Particle size is
      controlled through the emulsification parameters, yielding insulin-loaded
      microparticles. Particle recovery was compared using several washing protocols.
      Recovery strategies are proposed and the influence on particle mean size,
      morphology, recovery yield (RY), encapsulation efficiency, insulin release
      profile, and structural integrity of released insulin were evaluated. Spherical
      micron-sized particles loaded with insulin were produced. The recovery process
      was optimized, improving yield, and ensuring removal of residual oil from the
      particle surface. The optimum recovery strategy consisted in successive washing
      with a mixture of acetone/hexane/isopropanol coupled with centrifugation. This
      strategy led to small spherical particles with an encapsulation efficiency of 80%
      and a RY around 70%. In vitro release studies showed that alginate itself was not
      able to suppress insulin release in acidic media; however, this strategy
      preserves the secondary structure of insulin. Particles had a mean size lower
      than the critical diameter necessary to be orally absorbed through the intestinal
      mucosa followed by their passage to systemic circulation and thus can be
      considered as a promising technology for insulin delivery.

PMID- 17001631
TI  - Degradation of phenol by aerobic granules and isolated yeast Candida tropicalis.
AB  - Aerobic granules effectively degrade phenol at high concentrations. This work
      cultivated aerobic granules that can degrade phenol at a constant rate of 49 mg
      phenol/g x VSS/h up to 1,000 mg/L of phenol. Fluorescent staining and confocal
      laser scanning microscopy (CLSM) tests demonstrated that an active biomass was
      accumulated at the granule outer layer. A strain with maximum ability to degrade
      phenol and a high tolerance to phenol toxicity isolated from the granules was
      identified as Candida tropicalis via 18S rRNA sequencing. This strain degrades
      phenol at a maximum rate of 390 mg-phenol/g x VSS/h at pH 6 and 30 degrees C,
      whereas inhibitory effects existed at concentrations >1,000 mg/L. The Haldane
      kinetic model elucidates the growth and phenol biodegradation kinetics of the C.
      tropicalis. The fluorescence in situ hybridization (FISH) and CLSM test suggested
      that the Candida strain was primarily distributed throughout the surface layer of
      granule; hence, achieving a near constant reaction rate over a wide range of
      phenol concentration. The mass transfer barrier provided by granule matrix did
      not determine the reaction rates for the present phenol-degrading granule.

PMID- 17001632
TI  - Biodegradable cationic polyester as an efficient carrier for gene delivery to
      neonatal cardiomyocytes.
AB  - Viral-mediated gene delivery has been explored for the treatment and protection
      of cardiomyocytes, but so far there is only one report using cationic polymer for
      gene delivery to cardiomyocytes in spite of many advantages of polymer-mediated
      gene delivery. In this study, a cationic poly(beta-amino ester) (PDMA) with a
      degradable backbone and cleavable side chains was synthesized by Michael addition
      reaction. The toxicity of PDMA to neonatal mouse cardiomyocytes (NMCMs) was
      significantly lower than that of polyethyleneimine (PEI). PDMA formed stable
      polyplexes with pEGFP. The dissociation of the polyplexes could be triggered by
      PDMA degradation, and the dissociation time was tunable via the polymer/pEGFP
      ratio. In vitro transfection showed that PDMA was an effective and low toxic gene
      delivery carrier for NMCMs. The PDMA/pEGFP polyplexes transfected EGFP gene to
      NMCMs with about 28% efficiency and caused little death. In contrast, a
      significant portion of cardiomyocytes cultured with PEI/pEGFP died.

PMID- 17001633
TI  - Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat
      hippocampus.
AB  - Astroglia are integral components of synapse formation and maturation during
      development. Less is known about how astroglia might influence synaptogenesis in
      the mature brain. Preparation of mature hippocampal slices results in synapse
      loss followed by recuperative synaptogenesis during subsequent maintenance in
      vitro. Hence, this model system was used to discern whether perisynaptic
      astroglial processes are similarly plastic, associating more or less with
      recently formed synapses in mature brain slices. Perisynaptic astroglia was
      quantified through serial section electron microscopy in perfusion-fixed or
      sliced hippocampus from adult male Long-Evans rats that were 65-75 days old.
      Fewer synapses had perisynaptic astroglia in the recovered hippocampal slices
      (42.4% +/- 3.4%) than in the intact hippocampus (62.2% +/- 2.6%), yet synapses
      were larger when perisynaptic astroglia was present (0.055 +/- 0.003 microm2)
      than when it was absent (0.036 +/- 0.004 microm2) in both conditions.
      Importantly, the length of the synaptic perimeter surrounded by perisynaptic
      astroglia and the distance between neighboring synapses was not proportional to
      synapse size. Instead, larger synapses had longer astroglia-free perimeters where
      substances could escape from or enter into the synaptic clefts. Thus, smaller
      presumably newer synapses as well as established larger synapses have equal
      access to extracellular glutamate and secreted astroglial factors, which may
      facilitate recuperative synaptogenesis. These findings suggest that as synapses
      enlarge and release more neurotransmitter, they attract astroglial processes to a
      discrete portion of their perimeters, further enhancing synaptic efficacy without
      limiting the potential for cross talk with neighboring synapses in the mature rat
      hippocampus.

PMID- 17001634
TI  - Molecular analysis of successful cell line selection in transfected GS-NS0
      myeloma cells.
AB  - The production of recombinant proteins from mammalian cells is now an essential
      part of biotechnology. However, despite this importance, the detailed
      characteristics of good producing cell lines remain largely unknown. The
      industrially important GS-NS0 mammalian expression system is able to produce
      large amounts of protein from relatively few copies of recombinant genes. This
      makes GS-NS0 cell lines ideal candidates to study the consequence of recombinant
      plasmid transfection in mammalian cells. This study investigated the molecular
      features of a panel of 17 randomly chosen GS-NS0 cell lines engineered to produce
      a recombinant antibody. The research analysed antibody production via enzyme
      linked immunosorbent assay (ELISA), and investigated the molecular features of
      the transfectants by Northern, Southern and copy number analysis. The cell lines
      generated produced a range of antibody concentrations. In addition, for
      transfectants defined as producers of recombinant antibody there was a positive
      correlation between specific productivity and heavy chain mRNA expression. The
      use of Northern and Southern analysis allowed determination of the functional
      integrity of the transfected plasmid. Over 50% of the transfectants studied had
      molecular defects at the level of mRNA and/or cDNA. Cell lines were identified
      with suspected defects in the regulatory regions of transfected genes in addition
      to cell lines which lacked recombinant genes. Also, "false-positive" cell lines
      were generated which were able to overcome the GS selection pressure without
      producing any recombinant antibody. This article discusses these findings in
      relation to vector design.

PMID- 17001635
TI  - The thoracodorsal artery perforator flap with a vascularized scapular segment for
      reconstruction of a composite lower extremity defect.
AB  - High-energy trauma resulting in a composite defect of the lower extremity
      confronts the microvascular surgeon with more difficulties than do free flap
      reconstruction elsewhere in the body, since the choice of distant recipient
      vessels is particularly difficult. Combining principles of perforator flap
      surgery with those of composite tissue transfer, we designed a thoracodorsal
      artery perforator flap with a vascularized bone segment from the scapula for
      reconstruction of a composite lower extremity defect in a patient following a
      paragliding accident. This is the first report on the application of a composite
      thoracodorsal artery perforator flap with vascularized scapula in lower extremity
      reconstruction. Among its multiple advantages, such as preservation of latissimus
      dorsi function, it is a good tool for one-stage reconstruction of traumatic
      composite lower extremity defects because its low donor site morbidity and long
      vascular pedicle enables anastomosis placement outside the zone of injury.

PMID- 17001636
TI  - Kidney transplantation in the rat: a modified technique using hydrodissection.
AB  - Here, hydrodissection was compared with the conventional blunt instrumental
      dissection approach in a rat model of orthotopic kidney transplantation. Forty
      male Fisher and Lewis rats were used as kidney donors and recipients,
      respectively. After recipient nephrectomy, left kidney grafts were implanted
      orthotopically using standard microsurgical techniques. Two different methods of
      dissection of the graft and recipient vessels were used. In method A, the
      dissection was performed using blunt dissection with cotton-tipped sticks and
      jeweler's forceps (n = 20), and in method B, dissection was performed using water
      dissection technique (n = 20). Hydrodissection displayed the correct plane of
      dissection, reduced the operating time, and reduced the overall complication (P <
      0.001) and vasospasm (P < 0.05) rates. This is the first report of the use of
      hydrodissection in experimental transplantation. This atraumatic dissection
      technique does not require any special instruments, is fast, safe, demands less
      surgical skills, and may be useful in other transplantation models.

PMID- 17001637
TI  - Microsurgical reconstruction of chest wall defect after necrotizing fasciitis.
AB  - Chest wall necrotizing fasciitis is a rare and often fatal infection that usually
      requires extensive debridements and reconstructive procedures. We describe the
      therapeutical course of an uncommon case of perforating thoracic wound
      complicated with necrotizing fasciitis, with consecutive debridements and a
      resultant full-thickness subscapular defect. We agree that free flaps, although
      seldom required, must be considered when treating more complex defects.
      Latissimus dorsi free-flap was enough for pleural reconstruction and wall
      stabilization. There are no previous references in the literature to primary
      chest wall fasciitis treated successfully with microsurgical reconstruction.

PMID- 17001638
TI  - Intraspinal grafting procedures: spinal cord effects induced in the adult rat: a
      clinical, histopathological, and immunohistochemical study.
AB  - OBJECTIVE: Intraspinal grafting procedures using peripheral nerve grafts (PNG) or
      collagen guidance channels (CGC) have been recently used to treat brachial plexus
      injuries in humans and spinal cord injuries in animals. This study examined the
      effects of these procedures in the adult rat. METHODS: In adult rats, we
      performed an avulsion of left C5, C6, and C7 nerve roots, followed by a myelotomy
      of the left ventrolateral aspect of the spinal cord between C5 and C6. The rats
      were subsequently assigned to one of three groups: group A (n = 10), no
      additional procedure; group B (n = 10), implantation of a PNG following
      myelotomy; group C (n = 10), implantation of a CGC. Clinical evaluation was
      postoperatively assessed. Rats were euthanized at day 6 or 21. Spinal cord
      lesions induced by surgery were assessed by measuring depth and rostrocaudal
      extent. Reactive astrogliosis, as a reaction to neuroglial damage, was assessed
      by revealing the glial fibrillary acidic protein with immunochemistry method.
      RESULTS: No animal showed persistent neurological deficit at day 21. The depth
      and rostrocaudal extent of tissue damage was comparable in all groups at days 6
      and 21. At day 6, the astrocytic reaction observed at the myelotomy/implantation
      site was statistically stronger in group C (CGC). At day 21, the astrocytic
      reaction became identical in all groups. CONCLUSION: This study shows that
      grafting a PNG or a CGC into the spinal cord does not create significant
      additional iatrogenic effects and can be used in repair strategies to treat nerve
      root avulsions or spinal cord injuries.

PMID- 17001639
TI  - Microsurgical reconstruction of brachial artery injuries in displaced
      supracondylar fracture humerus in children.
AB  - Between March 2000 and March 2005, 840 children with grade III supracondylar
      humeral fractures presented for treatment, consecutively at our hospital. One
      hundred twenty had absent or diminished (detected by Doppler but not palpable)
      radial pulse on initial examination. Eighty-nine of these 120 children recovered
      pulse (palpable) after closed reduction and percutaneous pinning of the fracture.
      The remaining 31 children had persistent absent radial pulse. Twenty-two of the
      31 children had median nerve signs. Each of these 31 children was explored. The
      intraoperative findings were intact median nerve in all cases (neuropraxia),
      traumatic aneurysm with thrombus formation in 17 cases, complete injury of the
      brachial artery in 8 cases (loss of continuity), thrombosis in 3 cases, partial
      tear in 2 cases, and brachial artery entrapment in the fracture site in 1 case.
      Microsurgical reconstruction of the 31 brachial arteries was done as the
      following: reversed vein graft for 8 cases, excision and repair in 17 cases,
      partial repair in 2 cases, thrombectomy in 3 cases, and release of the brachial
      artery from the fracture site in 1 case. The average follow up was 26 months
      range (6-60) months. All children had excellent to good functional and cosmetic
      outcome except one who had Volkman's ischemic contracture, treated later by free
      functioning gracilis muscle transfer.

PMID- 17001640
TI  - Mathematical explanation of the buckling of the vessels after twisting of the
      microanastomosis.
AB  - BACKGROUND: To obtain free flap success, microvascular anastomosis must be
      perfectly constructed. External compression, twisting (torsion) of the
      anastomosis site, tension on the anastomosis site, and kinking of the pedicle
      must be avoided. Few experimental studies report the patency rates of rat vessels
      after twisting (torsion) of the microanastomosis: these results recently opened a
      discussion for the maximal angle of torsion, which can be impressed to a vessel
      in order to have the best patency rates. MATERIALS AND METHODS: To describe
      specifically the changing of shape of the vessels after the twisting of the
      microanastomosis, we extrapolate, to our experimental model (constituted by the
      femoral vessels of Wistar rats), the mathematical formula that engineers use to
      calculate the torsion of a beam when a torsion force is applied. The mathematical
      model used is the shell theory. Then, with a computer program using MATLAB, we
      could obtain the representation of these shapes at any degree of torsion.
      RESULTS: If a small load is applied to the vessels, it maintains its straight
      geometry. However, as soon as the load exceeds a critical value, which is a
      function of the vessel geometry and its mechanical characteristics, it snaps
      suddenly to a different equilibrium configuration. This phenomenon is called
      "buckling." When buckling occurs, wave-like deformations appear on the wall of
      the vessels. We calculate, in our experimental rat model, the critical twisting
      angle that induces buckling: maintaining a constant length of dissection of 25
      mm, a minimum twisting angle of 360 degrees + 161 degrees, or 105 degrees, is
      required, respectively, for the femoral artery or vein, to have the buckling
      phenomenon and the appearance of two waves and decreased section area.
      CONCLUSIONS: In surgical practice, with the parameters of our experimental Wistar
      rats model (vessel diameter, length of dissection), it is fundamental to be below
      105 degrees of torsion angle for the vein microanastomosis, in order to decrease
      its risk of failure.

PMID- 17001641
TI  - Culture media optimization for growth and phycoerythrin production from
      Porphyridium purpureum.
AB  - Porphyridium spp. is a red micro alga and is gaining importance as a source of
      valuable products viz., phycobiliproteins (PB), sulfated exopolysaccharides, and
      polyunsaturated fatty acids with potential applications in the food and
      pharmaceutical industries. In the present study, the effects of the major media
      constituents of Porphyridium species were studied using response surface
      methodology (RSM) on biomass yield, total PB and the production of phycoerythrin
      (PE). A second order polynomial can be used to predict the PB and PE production
      in terms of the independent variables. The independent variables such as the
      concentrations of sodium chloride, magnesium sulfate, sodium nitrate, and
      dipotassium hydrogen phosphate influenced the total PB and PE production. The
      optimum conditions showed that total PB was 4.8% at the concentration of sodium
      chloride 26.1 g/L, magnesium sulfate 5.23 g/L, sodium nitrate 1.56 g/L, and
      dipotassium hydrogen phosphate 0.034 g/L. In case of optimum PE production
      (3.3%), the corresponding values are 29.62, 6.11, 1.59, and 0.076 g/L,
      respectively. PE production depends greatly on the concentrations of chloride,
      nitrate, and sulfate as well as phosphate of which the former possess the maximum
      effect.

PMID- 17001642
TI  - Single base-pair substitutions in exon-intron junctions of human genes: nature,
      distribution, and consequences for mRNA splicing.
AB  - Although single base-pair substitutions in splice junctions constitute at least
      10% of all mutations causing human inherited disease, the factors that determine
      their phenotypic consequences at the RNA level remain to be fully elucidated.
      Employing a neural network for splice-site recognition, we performed a meta
      analysis of 478 disease-associated splicing mutations, in 38 different genes, for
      which detailed laboratory-based mRNA phenotype assessment had been performed.
      Inspection of the +/-50-bp DNA sequence context of the mutations revealed that
      exon skipping was the preferred phenotype when the immediate vicinity of the
      affected exon-intron junctions was devoid of alternative splice-sites. By
      contrast, in the presence of at least one such motif, cryptic splice-site
      utilization, became more prevalent. This association was, however, confined to
      donor splice-sites. Outside the obligate dinucleotide, the spatial distribution
      of pathological mutations was found to differ significantly from that of SNPs.
      Whereas disease-associated lesions clustered at positions -1 and +3 to +6 for
      donor sites and -3 for acceptor sites, SNPs were found to be almost evenly
      distributed over all sequence positions considered. When all putative missense
      mutations in the vicinity of splice-sites were extracted from the Human Gene
      Mutation Database for the 38 studied genes, a significantly higher proportion of
      changes at donor sites (37/152; 24.3%) than at acceptor splice-sites (1/142;
      0.7%) was found to reduce the neural network signal emitted by the respective
      splice-site. Based upon these findings, we estimate that some 1.6% of disease
      causing missense substitutions in human genes are likely to affect the mRNA
      splicing phenotype. Taken together, our results are consistent with correct donor
      splice-site recognition being a key step in exon recognition.

PMID- 17001643
TI  - Intrinsically unstructured N-terminal domain of bZIP transcription factor HY5.
AB  - The Arabidopsis HY5 protein is a basic leucine zipper (bZIP) transcription factor
      that promotes photomorphogenesis. HY5 binds directly to the promoters of light
      responsible element containing the G-box and thus regulates their transcriptional
      activity. The level and activity of HY5 are negatively regulated, in a light
      dependent manner, by interaction with the COP1 protein, which targets HY5 for
      proteasome-mediated degradation in the nucleus. Despite its essential roles in
      plant development, no structural information exists for HY5. In this article, we
      report the first structural and biophysical characterization of HY5. Using
      limited proteolysis in combination with mass spectrometry, circular dichroism,
      and nuclear magnetic resonance spectroscopy, we have deduced that the N-terminal
      77 amino acids of HY5 form a premolten globular structure, while amino acids 78
      110, which constitute the basic region (BR) of the protein, exist in a molten
      globule state. Our studies also revealed that the overall structural features of
      full-length HY5 are dominated largely by the disordered N-terminal domain,
      despite the existence of a bZIP domain at its C-terminus. We propose that HY5 is
      a member of the intrinsically unstructured protein (IUP) family, and that HY5
      functions as an unstructured protein and benefits from being the same, in vivo.

PMID- 17001644
TI  - Crosslinking of discrete self-assembled collagen threads: Effects on mechanical
      strength and cell-matrix interactions.
AB  - Bundles of threads extruded from type I collagen have been researched extensively
      as scaffolds to promote the repair and regeneration of torn tendons and
      ligaments. The success of these scaffolds has been limited by insufficient tissue
      ingrowth from the wound margin, which may be inhibited by the chemical or
      physical crosslinking treatment used to increase the mechanical properties and
      decrease the degradation rate of these scaffolds. Recently, self-assembled
      collagen threads extruded from solutions of type I collagen molecules were shown
      to possess ultimate tensile strengths and structural properties comparable to
      native tendon fibers; however the tissue response to these threads has yet to be
      determined. The goal of this study was to investigate the effects of various
      crosslinking techniques on the mechanical properties as well as the in vitro rate
      of new tissue ingrowth on these threads. Our findings indicate that the physical
      crosslinking techniques, dehydrothermal (DHT) or ultraviolet light (UV), most
      significantly improve the mechanical strengths of the threads, but most
      significantly decrease the rate of cell migration. In contrast, carbodiimide
      (EDC) crosslinking achieved sub-optimal strength generation, but demonstrated
      improved cell migration rates. Future studies will investigate the design of
      threads with surface biochemistries that maximize tissue ingrowth while
      maintaining the mechanical stability of the scaffold.

PMID- 17001645
TI  - iNOS-mediated generation of reactive oxygen and nitrogen species by biomaterial
      adherent neutrophils.
AB  - Infection due to implanted cardiovascular biomaterials is a serious complication
      initiated by bacterial adhesion to the surface of the implant. The release of
      reactive oxygen species by neutrophils, particularly superoxide anion, is a well
      known bactericidal mechanism. Additionally, nitric oxide (NO) has also been
      identified as an important cytotoxic mediator in acute and chronic inflammatory
      responses with enhanced NO production by upregulation of inducible nitric oxide
      synthase (iNOS). The interaction of NO and superoxide anion will result in the
      formation of peroxynitrite (OONO-), a potent cytotoxic oxidant. In this study, we
      have shown that biomaterial-induced neutrophil activation does not cause
      upregulation of iNOS and activation of iNOS-mediated pathways. However, NO and O2
      production does occur over time upon adhesion to a biomaterial and is modulated
      by biomaterial surface chemistry. With no stimulus, the polyethylene oxide
      modified polyurethane induced greater neutrophil activation than did the control
      as indicated by the increased production of NO and O2- over time. Adherent
      stimulated neutrophils generally produced lower amounts of NO over time in
      comparison with unstimulated cells. Furthermore, there is no evidence of
      peroxynitrite activity in unstimulated neutrophils adherent to the Elasthane 80A.
      However, upon stimulation with adherent Staphylococcus epidermidis, peroxynitrite
      formation did occur. Our results suggest that bactericidal mechanisms in
      neutrophils involving NO generation (NOS pathway) are further compromised than O2
      producing pathways (NADPH oxidase) upon exposure to biomaterials, resulting in a
      diminished microbial killing capacity, which can increase the probability of
      device-centered infections.

PMID- 17001646
TI  - Crystal structure of uncleaved L-aspartate-alpha-decarboxylase from Mycobacterium
      tuberculosis.
AB  - L-aspartate-alpha-decarboxylase (ADC) is a critical regulatory enzyme in the
      pantothenate biosynthetic pathway and belongs to a small class of self-cleaving
      and pyruvoyl-dependent amino acid decarboxylases. The expression level of ADC in
      Mycobacterium tuberculosis (Mtb) was confirmed by cDNA analysis, immunoblotting
      with an anti-ADC polyclonal antibody using whole cell lysate and immunoelectron
      microscopy. The recombinant ADC proenzyme from Mycobacterium tuberculosis
      (MtbADC) was overexpressed in E. coli and the protein structure was determined at
      2.99 A resolution. The proteins fold into the double-psi beta-barrel structure.
      The subunits of the two tetramers (there are eight ADC molecules in the
      asymmetric unit) form pseudo fourfold rotational symmetry, similar to the E. coli
      ADC proenzyme structure. As pantothenate is synthesized in microorganisms,
      plants, and fungi but not in animals, structure elucidation of Mtb ADC is of
      substantial interest for structure-based drug development.

PMID- 17001647
TI  - Docking of human interleukin-15 to its specific receptor alpha chain: correlation
      between molecular modeling and mutagenesis experimental data.
AB  - A structural model of the sushi domain of IL-15Ralpha was first obtained by
      homology modeling to study its interactions with IL-15 by means of molecular
      modeling, peptide scanning, and site-directed mutagenesis. From these
      experimental data, a putative interacting surface of IL-15Ralpha with a
      previously published IL-15 model was inferred: Leu25, Leu44, and Glu46 of IL-15
      and Arg35 of IL-15Ralpha were found to be key interfacial residues and were
      subsequently used as filters for the construction of docking solutions. Human IL
      15/IL-15Ralpha complexes were constructed in two stages, with a preliminary
      docking procedure, treating the two partners as rigid bodies and using these
      filters. In this first stage, two classes of docking solutions were
      characterized. From a topological point of view, each solution could be derived
      from the other by reverse orientation of one partner in relation to the other. In
      a second stage, several further energy refinements clearly favored one solution.
      Moreover, this unique docking solution was confirmed by molecular modeling of IL
      15 mutants previously built and tested in our laboratory. Finally, this complex
      model, which is a useful tool to study the IL-15/IL-15Ralpha interface, was
      topologically compared to IL-2/IL-2Ralpha complexes (previous model in the
      literature and recent crystal structure).

PMID- 17001648
TI  - Synthesis and characterization of biocompatible Fe3O4 nanoparticles.
AB  - In this study, magnetite (Fe3O4) nanoparticles with a size range of 8-20 nm were
      prepared by the modified controlled chemical coprecipitation method from the
      solution of ferrous/ferric mixed salt-solution in alkaline medium. In the
      process, two kinds of surfactant (sodium oleate and polyethylene glycol) were
      studied; then, sodium oleate was chosen as the apt surfactant to attain
      ultrafine, nearly spherical and well-dispersed (water-base) Fe3O4 nanoparticles,
      which had well magnetic properties. The size and size distribution of
      nanoparticles were determined by particle size analyzer. And the magnetite
      nanoparticles was characterized by X-ray powder diffraction (XRD) analysis,
      transmission electron microscopy (TEM), electron diffraction (ED) photography,
      Fourier transform infrared spectrometer (FT-IR), and vibrating-sample
      magnetometer (VSM). Also the effect of many parameters on the Fe3O4 nanoparticles
      was studied, such as reaction temperature, pH of the solution, stirring rate and
      concentration of sodium oleate. And the 5-dimethylthiazol-2-yl-2,5-
      diphenyltetrazolium bromide (MTT) assay was performed to evaluate the
      biocompatibility of magnetite nanoparticles. The results showed that the Fe3O4
      nanoparticles coated by sodium oleate had a better biocompatibility, better
      magnetic properties, easier washing, lower cost, and better dispersion than the
      magnetite nanoparticles coated by PEG.

PMID- 17001649
TI  - Thermal-mechanical study of functionally graded dental implants with the finite
      element method.
AB  - This article investigates the thermal-mechanical performance of
      hydroxyapatite/titanium (HA/Ti) functionally graded (FG) dental implants with the
      three-dimensional finite element method. The stresses induced by occlusal force
      for the present HA/Ti FG implant are calculated to compare with the corresponding
      stresses for the titanium dental implant. Thermal-mechanical effect of
      temperature variation due to daily oral activity is also studied. The HA/Ti FG
      dental implant performance is evaluated against the maximum von Mises stress,
      which is the general performance indicator, the first principal/tensile stress
      for mechanical failure of implant-bone-bond and the third principal/compressive
      stress for bone absorption. Simulation results indicate that under the influence
      of occlusal force only, the FG implants with different HA fraction along the
      implant length perform almost equally well, while the titanium implant sustains
      much higher von Mises stress. However, when thermal stress is also considered,
      the FG implant having HA fraction exponential index of m = 2 with temperature
      decrease of 20 degrees C yields the highest first principal and von Mises
      stresses among all the FG and titanium implants.

PMID- 17001650
TI  - Human gingival fibroblast response to electropolished NiTi surfaces.
AB  - In the present study the in vitro biocompatibility of electropolished NiTi sheets
      is investigated. The assessment of cytotoxic effects due to potential Ni leaching
      from metal sheets was performed in direct contact with primary human fibroblast
      cultures using the 5-bromo-2'-deoxyuridine cell proliferation assay and
      morphologic studies via light microscopy and scanning electron microscopy. To
      assess toxic effects related to Ni-ions release, cells cultured in the presence
      of increasing concentrations of Ni(2+) (NiSO(4).6H(2)O) served as positive
      controls. It is shown that while the addition of NiSO(4) caused severe
      proliferation decrease (approximately 80%) and morphologic damage at a
      concentration of 50 mg/L Ni(2+) no negative effects were observed in fibroblasts
      cultured in the presence of electropolished NiTi sheets. The results are
      discussed in terms of surface topography effects on the biocompatibility of NiTi
      shape memory alloys.

PMID- 17001651
TI  - Hemostatic properties of glucosamine-based materials.
AB  - Glucosamine- and N-acetyl glucosamine-containing polymers are being used in an
      increasing number of biomedical applications, including in products for surface
      (topical) hemostasis. The studies presented here investigate the relationship
      between the structure (conformation) and function (activation of hemostasis) of
      glucosamine-based materials. Several polymer systems were studied, including
      fibers isolated from a microalgal source containing poly-N-acetyl glucosamine
      polymers that are organized in a parallel, hydrogen-bonded tertiary structure and
      can be chemically modified to an antiparallel orientation; and gel formulation
      derivatives of the microalgal fibers consisting of partially deacetylated (F2
      gel) and fully deacetylated (F3 gel) polymers. Comparison of the properties of
      the poly-N-acetyl glucosamine fiber-derived materials with chitin, chitosan, and
      commercial chitosan-based products are presented. Several studies were performed
      with the glucosamine-based materials, including (1) an analysis of the ability of
      materials to activate platelets and turnover of the intrinsic coagulation
      cascade, (2) an examination of the viscoelastic properties of mixtures of
      platelet-rich plasma and the glucosamine-based materials via thromboelastography,
      and (3) scanning electron microscopic studies to examine the morphology of the
      glucosamine-based materials. The results presented demonstrate that hemostatic
      responses to the glucosamine-based materials studied are highly dependent on
      their chemical nature and tertiary/quaternary structure. The unique natural
      microalgal fibers were found to have strongly prohemostatic activity compared to
      the other materials studied.

PMID- 17001652
TI  - Computational and experimental approaches for assessing the interactions between
      the model calycin beta-lactoglobulin and two antibacterial fluoroquinolones.
AB  - Norfloxacin and levofloxacin, two fluoroquinolones of different bulk, rigidity
      and hydrophobicity taken as model ligands, were docked to one apo and two holo
      crystallographic structures of bovine beta-lactoglobulin (BLG) using different
      computational approaches. BLG is a member of the lipocalin superfamily.
      Lipocalins show a typical b-barrel structure encompassing an internal cavity
      where small hydrophobic molecules are usually bound. Our studies allowed the
      identification of two putative binding sites in addition to the calyx. The rigid
      docking approximation resulted in strong repulsive forces when the ligands were
      docked into the calyx of the apo form. On the contrary, hindrance was not
      experienced in flexible docking protocols whether on the apo or on the holo BLG
      forms, due to allowance for side chain rearrangement. K(i) between 10(-7) and 10(
      6) M were estimated for norfloxacin at pH 7.4, smaller than 10(-5) M for
      levofloxacin. Spectroscopic and electrophoretic techniques experimentally
      validated the occurrence of an interaction between norfloxacin and BLG. Changes
      in chemical shift and dynamic parameters were observed between the (19)F NMR
      spectra of the complex and of the ligand. A K(i) (ca 10(-7) M) comparable with
      the docking results was estimated through a NMR relaxation titration.
      Stabilization against unfolding was demonstrated by denaturant gradient gel
      electrophoresis on the complex versus apo BLG. NMR experimental evidence points
      to a very loose interaction for ofloxacin, the racemic mixture containing
      levofloxacin. Furthermore, we were able to calculate in silico K(i)'s comparable
      to the published experimental values for the complexes of palmitic and retinoic
      acid with BLG.

PMID- 17001653
TI  - Factors affecting the structure and properties of an injectable self-setting
      calcium phosphate foam.
AB  - One of the main challenges in the investigation on calcium phosphate cements
      (CPC) lies in the introduction of macroporosity, without loosing the self-setting
      ability and injectability, characteristic of the cement-type materials. The
      benefits of macroporosity are related to the enhancement of bone regeneration
      mechanisms, such as angiogenesis and tissue ingrowth. In this work, the
      feasibility to obtain self-setting injectable macroporous hydroxyapatite foams by
      the incorporation of a protein-based foaming agent to a CPC is demonstrated.
      Albumen is combined with an alpha-tricalcium phosphate [Ca3(PO4)2, alpha-TCP]
      paste, which hydrolyzes to a calcium deficient hydroxyapatite during the setting
      reaction. A systematic study is presented, where the effect of different
      processing parameters is analyzed in terms of porosity, setting properties,
      injectability, and compressive strength. Self-setting foams with porosities up to
      70%, which maintain their porous structure after injection, are obtained. These
      injectable foams can be used both for direct in vivo applications and for the
      fabrication of low temperature tissue engineering scaffolds.

PMID- 17001654
TI  - Histological assessment of titanium and polypropylene fiber mesh implantation
      with and without fibrin tissue glue.
AB  - Polypropylene (PP) and titanium (Ti) meshes are well-known surgical implants that
      provoke a relative low foreign body reaction. Firm stabilization of the implant
      is important to prevent migration and subsequent failure of the operation. Fibrin
      tissue glues are commercially available adhesives and are widely accepted and
      applied in the medical field for hemorrhage, surgical bleeding, support of wound
      healing, wound and tissue gluing, sealing, and closure but also as antiadhesive
      agent in certain applications. The objective of this study was to evaluate the
      additional histological effect of fibrin glue application combined with two
      different types of meshes. Six pieces of mesh of each were subcutaneously
      implanted for 3, 6, and 12 weeks, with and without fibrin glue. After excision,
      processing, and staining, light microscopic analysis was performed on the
      sections, using subjective histological description and histomorphometry. Capsule
      quality, capsule thickness, interstitial quality, and total score were evaluated.
      To compare the samples with glue and without glue, analysis of variance (ANOVA)
      tests were carried out. No complications were observed. In general, the glue
      remnants remained visible at 3 and 6 weeks of implantation, accompanied by an
      inflammatory reaction and macrophage activity. At 12 weeks, all samples showed
      good tissue integration without evidence of glue. Evidently, the samples with
      glue demonstrated a prolonged inflammatory response and were surrounded by
      fibrous tissue capsules that were significantly thicker compared with the samples
      without glue (p < 0.05).

PMID- 17001655
TI  - Relationship of solvent to the photopolymerization process, properties, and
      structure in model dentin adhesives.
AB  - The ratio of the double-bond content of monomer to polymer, i.e. degree of
      conversion (DC) has been used frequently as a convenient means of comparing the
      behavior and properties of dental composites and adhesives. The purpose of this
      investigation was to study the relationship of photopolymerization processes,
      bulk properties, and structure using model dentin adhesives cured in the presence
      of different ethanol content as an example. There was little difference in the DC
      of model BisGMA-based adhesives cured in the presence of ethanol concentrations
      ranging from 0 to 40 wt %, but there were substantial differences in the
      mechanical properties. Ultimate tensile strength (UTS) and modulus of elasticity
      decreased with an increase in ethanol content. Polymer structure was revealed by
      thermal behavior in the glass transition temperature (Tg) region; these
      measurements were obtained by modulated temperature differential scanning
      calorimetry (MTDSC) technology, which removes the competing irreversible effects
      associated with release of volatiles and residual curing. Glass transition
      temperature of model adhesives decreased substantially with an increase in
      ethanol content. The DC based on the quantity of remaining double bond has been
      used extensively to characterize and provide a relative assessment of the quality
      of dentin adhesives and dental composites. Since polymers differing in linearity,
      and therefore crosslink density, may have a similar degree of conversion, the
      measurement of monomer/polymer conversion does not necessarily provide complete
      representation of the quality or durability of the polymer structure.

PMID- 17001656
TI  - One step synthesis of silver nanorods by autoreduction of aqueous silver ions
      with hydroxyapatite: An inorganic-inorganic hybrid nanocomposite.
AB  - In this report, a novel method for the synthesis of silver nanoparticles on the
      surface of hydroxyapatite is described. Hydroxyapatite crystals are synthesized
      from acid mineralized solution, a byproduct of bone glue industries, by a simple
      chemical precipitation method, which results in the formation of hydroxyapatite
      nanocrystals. The reduction of silver ions occurs by the electron transfer from
      the hydroxyl groups on the surface of hydroxyapatite. This results in the
      formation of silver nanorods and needle shaped nanoparticles that are bound on
      the surface of hydroxyapatite, and the observed silver nanocrystals show
      anisotropic structure. Thus, hydroxyapatite crystals can be used as a new class
      of inorganic scaffolds for the synthesis of nanomaterials with implications in
      designing inorganic-inorganic hybrid nanocomposites for different applications.

PMID- 17001657
TI  - Amelogenin gene splice products A+4 and A-4 implanted in soft tissue determine
      the reorientation of CD45-positive cells to an osteo-chondrogenic lineage.
AB  - Several molecules such as bone morphogenetic protein-7, bone sialoprotein (BSP),
      or amelogenin gene splice products (A+4 or A-4) have been shown to induce
      reparative dentin formation in a rat model. However, at the moment, the origin
      and the mechanism of differentiation of the pulp cells stimulated by the
      bioactive molecules remain poorly understood. The present investigation was
      undertaken to validate an ectopic oral mucosal mouse model to evaluate the
      effects of amelogenin gene splice product implantation in a non-mineralizing
      tissue. Agarose beads, alone or coated with amelogenin gene splice products, were
      implanted in the mucosa of the cheeks in mouse. An immunohistochemical
      characterization of the recruited cells was undertaken for 3 days, 8 days, and 30
      days after the implantation. The results showed that the implantation of agarose
      beads in mucosa induced the recruitment of inflammatory CD45 positive cells. When
      the beads were coated with amelogenin gene splice products (A+4 or A-4), the
      expression of osteo-chondrogenic markers (RP59, Sox9, or BSP) was also observed.
      However, no mineralization nodule was observed, even after 30 days of
      implantation. The present investigation suggests that amelognin gene splice
      products have the capacity of recruiting among inflammatory cell mesenchymal
      progenitors that eventually differentiate into osteo-chondrogenic cells.
      Altogether, the results obtained in the pulp model and the present data suggest
      the existence of different pathways of cell recruitment and differentiation in
      different cellular environments.

PMID- 17001659
TI  - BMP and LIF signaling coordinately regulate lineage restriction of radial glia in
      the developing forebrain.
AB  - The earliest radial glia are neural stem cells that guide neural cell migration
      away from ventricular zones. Subsequently, radial glia become lineage restricted
      during development before they differentiate into more mature cell types in the
      CNS. We have previously shown that subpopulations of radial glial cells express
      markers for glial and neuronal restricted precursors (GRPs and NRPs) in
      expression patterns that are temporally and spatially regulated during CNS
      development. To characterize further the mechanism of this regulation in rat
      forebrain, we tested whether secreted factors that are present during development
      effect lineage restriction of radial glia. We show here that in radial glial
      cultures LIF/CNTF up-regulates, whereas BMP2 down-regulates GRP antigens
      recognized by monoclonal antibodies A2B5/4D4. These activities combined with
      secretion of BMPs dorsally and LIF/CNTF from the choroid plexus provide an
      explanation for the graded distribution pattern of A2B5/4D4 in dorso-lateral
      ventricular regions in vivo. The regulation by LIF/CNTF of A2B5/4D4 is mediated
      through the JAK-STAT pathway. BMP2 promotes expression on radial glial cells of
      the NRP marker polysialic acid most likely by regulating N-CAM expression itself,
      as well as at least one polysialyl transferase responsible for synthesis of
      polysialic acid on N-CAM. Taken together, these results suggest that generation
      of lineage-restricted precursors is coordinately regulated by gradients of the
      secreted factors BMPs and LIF/CNTF during development of dorsal forebrain.

PMID- 17001660
TI  - In vitro characterization of SLV308 (7-[4-methyl-1-piperazinyl]-2(3H)
      benzoxazolone, monohydrochloride): a novel partial dopamine D2 and D3 receptor
      agonist and serotonin 5-HT1A receptor agonist.
AB  - Present Parkinson's disease treatment strategies are far from ideal for a variety
      of reasons; it has therefore been suggested that partial dopamine receptor
      agonism might be a potential therapeutic approach with potentially fewer side
      effects. In the present study, we describe the in vitro characterization of the
      nonergot ligand SLV308 (7-[4-methyl-1-piperazinyl]-2(3H)
      benzoxazolonemonohydrochloride). SLV308 binds to dopamine D(2), D(3), and D(4)
      receptors and 5-HT(1) (A) receptors and is a partial agonist at dopamine D(2) and
      D(3) receptors and a full agonist at serotonin 5-HT(1) (A) receptors. At cloned
      human dopamine D(2,L) receptors, SLV308 acted as a potent but partial D(2)
      receptor agonist (pEC(50) = 8.0 and pA(2) = 8.4) with an efficacy of 50% on
      forskolin stimulated cAMP accumulation. At human recombinant dopamine D(3)
      receptors, SLV308 acted as a partial agonist in the induction of [(35)S]GTPgammaS
      binding (intrinsic activity of 67%; pEC(50) = 9.2) and antagonized the dopamine
      induction of [(35)S]GTPgammaS binding (pA(2) = 9.0). SLV308 acted as a full 5
      HT(1) (A) receptor agonist on forskolin induced cAMP accumulation at cloned human
      5-HT(1) (A) receptors but with low potency (pEC(50) = 6.3). In rat striatal
      slices SLV308 concentration-dependently attenuated forskolin stimulated
      accumulation of cAMP, as expected for a dopamine D(2) and D(3) receptor agonist.
      SLV308 antagonized the inhibitory effect of quinpirole on K(+)-stimulated [(3)H]
      dopamine release from rat striatal slices (pA(2) = 8.5). In the same paradigm,
      SLV308 had antagonist properties in the presence of quinpirole (pA(2) = 8.5), but
      the partial D(2) agonist terguride had much stronger antagonistic properties. In
      conclusion, SLV308 combines high potency partial agonism at dopamine D(2) and
      D(3) receptors with full efficacy low potency serotonin 5-HT(1) (A) receptor
      agonism and is worthy of profiling in in vivo models of Parkinson's disease.

PMID- 17001661
TI  - Racial disparity in survival among patients with advanced/recurrent endometrial
      adenocarcinoma: a Gynecologic Oncology Group study.
AB  - BACKGROUND: Previous studies have reported shorter survival of black women
      compared with white women who had advanced/recurrent endometrial cancer. It has
      been suggested that this may reflect racially based differences in treatment.
      METHODS: The authors retrospectively reviewed data from 169 black women and 982
      white women with International Federation of Gynecologic Oncology (FIGO) Stage
      III, Stage IV, or recurrent endometrial carcinoma who were participants in 1 of 4
      Gynecologic Oncology Group randomized treatment trials of doxorubicin alone or
      combined with paclitaxel and/or cisplatin. Demographic, histologic, treatment,
      and outcome data were analyzed to estimate survival, and between-group
      comparisons were performed. RESULTS: The pooled data revealed that black women
      were more likely to have papillary serous histology (P < .001), Stage IV disease
      (P < .001), and higher tumor grade (P < .001) compared with white women, and
      survival was worse among black women than among white women (median survival,
      10.6 months vs. 12.2 months, respectively; P < .001). A Cox proportional hazards
      regression analysis that was adjusted for performance status, disease stage,
      tumor histology, tumor grade, and treatment demonstrated worse survival for black
      women (hazards ratio, 1.26, 95% confidence interval, 1.06-1.51; P = .010).
      CONCLUSIONS: The data from a large group of women with advanced/recurrent
      endometrial cancer suggested that a racial disparity in survival persists,
      despite the finding that black women and white women received similar treatment.
      Although the causes of racial disparity in endometrial cancer remain to be
      elucidated, socioeconomic, biologic, and cultural factors should be investigated
      to identify the etiologic origins of this multifactorial healthcare problem.

PMID- 17001662
TI  - Significant regional variation in adequacy of lymph node assessment and survival
      in gastric cancer.
AB  - BACKGROUND: Lymph node (LN) status is a major determinant of prognosis and
      treatment of gastric adenocarcinoma. The 1997 American Joint Commission on
      Cancer/Union Internationale Contre le Cancer guidelines were revised, requiring
      examination of > or =15 LN for staging. METHODS: We investigated compliance with
      these guidelines and the correlation with overall survival (OS) by analyzing
      10,807 resected gastric cancers in the Surveillance, Epidemiology and End Results
      (SEER) database, 1988-2002. Kaplan-Meier survival curves were constructed;
      survival was compared by using Cox proportional hazards. RESULTS: Overall, 29% of
      cases had > or =15 LN examined. After 1997, the median number of LN assessed
      increased from 9 to 10 (P < .0001). Factors predictive of adequate LN assessment
      (ALNA) were higher stage, worse grade, age <74 years, later year of diagnosis,
      nonwhite race, more extensive surgery, female sex, and SEER region. Differences
      in the rate of ALNA between regions were noted, ranging from 19.7-53% (P <
      .0001). Of T1N0 patients, 19% had ALNA. Improved OS was predicted by earlier
      stage, lower grade, marital status, Asian race, younger age, T-stage, female sex,
      SEER region, and ALNA. Median OS was highest in the region with the best ALNA
      rate and worst in the region with the lowest (33 mos vs. 17 mos, P < .0001).
      Inadequate LN assessment led to poorer survival at every stage (P < .001).
      CONCLUSION: The overwhelming majority of patients have an inadequate LN
      assessment. ALNA was associated with improved OS, with significant variation
      across regions. Understaging due to inadequate LN assessment may affect
      eligibility for adjuvant therapy. Education is required to improve LN retrieval.

PMID- 17001663
TI  - "Open y" technique in vessel diameter discrepancy.
AB  - For the last 20 years, free tissue transfers have increasingly become the
      mainstay of plastic surgery. Size discrepancy between the vessels during tissue
      transfers are frequently encountered in clinical practice, and this may
      potentially be an important factor in the patency of anastomosis. In our clinic,
      we first studied a rat model and a fresh sheep cadaver to improve the diameter
      discrepancy in microvascular anastomosis with "open y" technique. At the end of
      our research, we progressed to success, and the open y technique was applied to
      nine patients in our clinic with a diameter discrepancy in microvascular
      anastomosis. After finding the bifurcation of vessels (artery, vein, or a vein
      graft) that are prepared for anastomosis, a distal cut of 2-3 mm was made for the
      anastomosis, which is considered to increase the diameter. Both legs of the
      resultant "y"-shaped vessel were united after inserting the microscissors from
      one leg and exiting from the other. Performing an end-to-end anastomosis between
      the vessels, we obtain an increase in the diameter. By using this method, we
      eliminated the diameter discrepancy in microvascular anastomosis in nine patients
      in our clinic. There was not any flap loss. To increase the usage of this
      technique, when we come across a problem of size discrepancy, it is important to
      use the open y technique, both to the recipient vessels, donor vessels, and to
      the vein grafts. Owing to its high prevalence and the ease of application, we are
      convinced that this is a suitable technique in appropriate cases.

PMID- 17001664
TI  - The Eighth Congress of the European Federation of Societies for Microsurgery.

PMID- 17001665
TI  - Craniofacial and dental phenotype of Smith-Magenis syndrome.
AB  - The aim of this study was to assess and characterize dental and craniofacial
      findings in individuals with a confirmed diagnosis of Smith-Magenis syndrome
      (SMS). Extraoral and intraoral examination including dental and craniofacial
      radiographs and three-dimensional facial photoimaging were performed for 15 cases
      between ages 4 and 19 years old. Tooth agenesis (13/15 cases) affecting primarily
      the mandibular second premolars and taurodontism (13/15 cases) were common
      findings. Dilaceration of the tooth roots was present in one-third of the cases.
      At least one dental anomaly was present in each case. These findings occur with
      greater frequency than in the general population (P < 0.001). An age-related
      increase in decayed and restored teeth was found. Poorer oral hygiene, increased
      dental plaque, and increased gingival inflammation progressed from childhood to
      teenage years. Radiographic findings suggest the prognathic appearance is not
      caused by excessive mandibular growth. Other findings including protrusion of the
      mandibular anterior teeth, increased bony chin size, and macroglossia were noted,
      which may contribute to the prognathic appearance. The high prevalence of dental
      anomalies (>90%) further expands the phenotype and indicates that dental
      evaluation may aid in the diagnosis of SMS.

PMID- 17001666
TI  - Facial and Oral Structures: Molecular Perspectives. Proceedings of the 13th
      Annual Robert J. Gorlin Conference on Dysmorphology, October 22-23, 2005,
      Minneapolis, Minnesota, USA.

PMID- 17001667
TI  - SIX3 mutations with holoprosencephaly.
AB  - Here, we report six Brazilian patients with holoprosencephaly caused by SIX3
      mutations. Missense mutations were more common than frameshift mutations.
      Comparison of patients with missense versus frameshift mutations was essentially
      unremarkable. Our cases suggest that SIX3 mutations result in a more severe
      phenotype than other gene mutations for holoprosencephaly. One patient had a
      double SIX3 mutation, which has not been reported previously. In our SIX3
      mutations, three were transmitted by the paternal side, two were transmitted by
      the maternal side, and one was a de novo event. Mutations in normal parents with
      severe involvement of their offspring does not allow prediction of phenotypic
      severity, which makes genetic counseling difficult.

PMID- 17001668
TI  - PTCH mutations in four Brazilian patients with holoprosencephaly and in one with
      holoprosencephaly-like features and normal MRI.
AB  - We report five Brazilian probands with PATCHED (PTCH) mutations and highly
      variable phenotypes with holoprosencephaly in four cases and holoprosencephaly
      like facial features with a normal MRI in a fifth case. Three of our mutations
      were novel: Ala443Gly, Val751Gly, and Val908Gly. Two patients had the same
      mutation (Val908Gly), but were phenotypically different: alobar
      holoprosencephaly, absent nasal septum, and midline cleft lip-palate in one case,
      and lobar holoprosencephaly, macrocephaly, hypertelorism, clefting of the nose,
      severe microphthalmia, and a single maxillary central incisor in the other. One
      of our patients had a Thr1052Met mutation, holoprosencephaly-like facial
      features, and a normal MRI. Ming et al. [(2002); Hum Genet 110:297-301] reported
      an identical mutation, but with alobar holoprosencephaly.

PMID- 17001669
TI  - Holoprosencephaly-like phenotype: clinical and genetic perspectives.
AB  - We report 22 patients with normal neuropsychological development and a
      holoprosencephaly-like (HPE-like) phenotype screened for SHH, SIX3, TGIF, and
      GLI2. These patients were divided into two groups: (1) 6 patients with SHH and
      GLI2 mutations and (2) 16 patients with no detectable mutations. We discuss the
      phenotypic manifestations, evolution of the phenotype, and neuroimaging in the
      two groups. Conclusions about the HPE-like phenotype include (1) initial
      appearance as an unusually wide, and very severe unilateral cleft lip-palate in
      some cases; (2) variability with the expression of minor anomalies in some cases,
      such as single maxillary central incisor; (3) identifiable mutations in some
      cases and absence of mutations in others; (4) essentially normal MRI in the most
      cases (pituitary tumor in two cases and choroid fissure cyst in one case in Group
      1; empty sella turcica in one case in Group 2); (5) intelligence within the
      normal range; and (6) familial aggregation in some instances. Implications
      include (1) thorough examination of family members for minor anomalies; (2) MRI
      and developmental assessment for the proband; and (3) molecular analysis.

PMID- 17001670
TI  - Single maxillary central incisor, holoprosencephaly, and holoprosencephaly-like
      phenotype.
AB  - Three patients--one with alobar holoprosencephaly and two with a
      holoprosencephaly-like phenotype--are reported with no identifiable mutations. In
      each case, one parent had a single maxillary central incisor (SMCI). We briefly
      review the holoprosencephaly-like phenotype and present a table of 25 conditions
      with SMCI.

PMID- 17001671
TI  - Contiguous gene syndrome of holoprosencephaly and hypotrichosis simplex:
      association with an 18p11.3 deletion.
AB  - We report a patient with a unique combination of features, including
      microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic
      pituitary gland; hypothyroidism; alopecia universalis; single maxillary central
      incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and
      scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10).
      The constellation of anomalies appears to represent a contiguous gene syndrome
      caused, at least in part, by deletion of TGIF and the gene responsible for
      hereditary hypotrichosis simplex. The phenotype of our patient differs other
      reported patients with del(18p). Possible explanations include (1) the effects of
      a different deleted region, (2) a positional effect caused by a gene close by, or
      (3) by interruption of a different gene resulting from chromosomal translocation.

PMID- 17001672
TI  - A newly recognized polyosteolysis/hyperostosis syndrome.
AB  - We report a newly recognized bone disorder consisting of polyostotic expansile
      osteolysis affecting long bones and iliac bones; hyperostosis of the skull,
      thoracic cage, and medial portion of both clavicles; pectus carinatum;
      gigantiform synovial masses of the elbows and knees; atrial septal defect;
      cardiomegaly; unilateral cryptorchidism; and mental deficiency. Affected bones
      can be grouped into four general types of skeletal pathology: (1) expansile
      osteolysis, (2) osteolysis without expansion, (3) expansion without osteolysis,
      and (4) hyperostosis. Some bones remained unaffected. We have named the condition
      "polyosteolysis/hyperostosis syndrome." It is clearly at variance with any
      previously reported bone disorder, including familial expansile osteolysis,
      juvenile Paget disease, and McCune-Albright syndrome (and polyostotic fibrous
      dysplasia). Because our patient shared some features in common with juvenile
      Paget disease, we thought that mutational analysis of TNFRSF11B was indicated,
      even though our patient had some manifestations not found in juvenile Paget
      disease. Direct sequencing failed to identify a TNFRSF11B mutation. Because the
      parents of our propositus were first cousins suggests that
      polyosteolysis/hyperostosis syndrome may possibly have autosomal recessive
      inheritance.

PMID- 17001673
TI  - Transcriptome profiling in clinical breast cancer: from 3D culture models to
      prognostic signatures.
AB  - Early detection has been one of the most effective strategies to control the
      growing cancer burden. The power of earlier detection has been demonstrated by
      the impact of pap-smear, mammography, and PSA tests on cancer patient treatment
      and survival. These tests benefit patients independent of their genetic
      background or race. However, in many cases, we are still losing the battle
      against cancer because patients that initially presented with low-grade disease
      progress rapidly to aggressive forms of the disease. As of yet, we have limited
      means to predict a particular patient's fate or to specifically treat subtypes of
      cancer. A combination of earlier detection and targeted therapy, based on
      information from transcriptome analysis, could be a powerful ally in this battle.
      The theme of this review article is to briefly summarize innovative strategies
      using three-dimensional (3D) cell cultures of human mammary epithelial cells to
      predict clinical outcome in breast cancer. This strategy has the potential to
      further enhance our understanding of breast cancer biology and to contribute to
      the identification of biologically significant bio-markers that are also useful
      drug targets.

PMID- 17001674
TI  - A role of novel serpin maspin in tumor progression: the divergence revealed
      through efforts to converge.
AB  - Maspin, a 42 kDa protein, belongs to the serine protease inhibitor (serpin)
      superfamily and is more closely related to the ovalbumin-like serpin subfamily
      (ov-serpins). More than a decade after the discovery of the maspin gene, our
      pursuit of the molecular mechanisms of maspin revealed a significant divergence
      of maspin from other serpins. This review article summarizes recent advances in
      the identification of maspin-binding proteins and the potential underlying
      molecular mechanisms of maspin in tumor progression. Specifically, the molecular
      interactions of maspin with the cell surface-associated pro-urokinase-type
      plasminogen activator (pro-uPA) and intracellular histone deacetylase 1 (HDAC1)
      are highlighted. Our new evidence suggests a new paradigm that maspin acts as a
      serpin-like molecule to inhibit serine protease-like targets. From an evolution
      point of view, the uniquely important function of maspin in development and tumor
      progression is likely due to its ancestral sequence code, and accordingly, its
      novel "meta"-serpin structure. It is reasonable to hypothesize that the
      conservation of a serine protease-like catalytic center in many molecules
      requires the co-existence of endogenous antagonists. The unique inhibitory
      interaction of maspin with both HDAC1 and pro-uPA might not be substituted by
      other serpins that have evolved to acquire higher target specificities. Thus,
      tumor suppressive maspin offers a unique therapeutic opportunity.

PMID- 17001675
TI  - Discovering innate immunity genes using differential display: a story of RNA
      helicases.
AB  - In this review we discuss the current literature for RNA helicases in response to
      RNA virus infection. We show the use of Differential Display Reverse
      Transcription PCR methodology (DD) to analyze virus-host interactions and we
      present current findings in dengue virus-induced gene expression of RNA
      helicases.

PMID- 17001676
TI  - Linkage between EGFR family receptors and nuclear factor kappaB (NF-kappaB)
      signaling in breast cancer.
AB  - In the United States there are 225,000 new cases of invasive breast cancer
      annually, and at least 50,000 women are diagnosed with ductal carcinoma in situ
      (DCIS). Breast cancer is a collection of disorders of mammary epithelial cells
      with distinct pathological characteristics and diverse clinical manifestations.
      Breast cancers are divided broadly into four classes by the level of the
      biomarkers HER2 (erbB2/neu) and the estrogen receptor (ER). Histologic grade is
      also an important modifier of breast cancer taxonomy and behavior. Broadly
      speaking, breast cancer can be divided into those that are HER2-positive,
      containing cancers that are both ER-positive and negative, cancers that are ER
      positive and divided into high-grade and low-grade tumors, and the remaining but
      important class of cancers that are both ER-negative and HER2-negative. These
      last cancers are called basal-like and were first recognized as a distinct group
      by gene expression arrays. Nuclear factor kappaB (NF-kappaB) is family of
      multifunctional transcription factors that when activated generate pleotrophic
      changes in target cells. Elevated levels of active NF-kappaB are detected in many
      human diseases including breast cancers. High-level active NF-kappaB is detected
      in specific subclasses of breast cancers briefly described above, predominantly
      in ER-negative and epidermal growth factor family receptor (EGFR) overexpressing
      breast cancers (predominantly HER2 amplified cancers). This article is focused on
      the role of NF-kappaB activation initiated by the EGFR family receptors in
      subclasses of breast cancer. The combined influence of EGFR family receptors and
      NF-kappaB signaling on the transformation of ER-negative human mammary epithelial
      cell is illustrated.

PMID- 17001677
TI  - From differential display to DNA microarrays--a personal account.
AB  - This article is a tribute to Dr. Arthur Pardee, one of the most innovative and
      brilliant scientists of our time, on the occasion of his 85th birthday. In this
      partially perspective and partially review piece, I look back how fate, by twist
      and turn, has led me eventually to his lab at Harvard where we worked out the
      Differential Display technology from scratch, how the method has revolutionized
      the field of gene expression analysis and where DD is taking us in the "era" of
      DNA microarrays.

PMID- 17001678
TI  - Pediatric perspective on prenatal counseling for myelomeningocele.
AB  - BACKGROUND: Over the past 35 years, advances in the prenatal diagnosis of spina
      bifida using ultrasound and laboratory testing have increased the number of
      patients seeking prenatal counseling. METHODS: Traditionally, this counseling has
      been provided by practitioners with little direct experience in the care of
      individuals with spina bifida across their life span. RESULTS: Physicians
      experienced in the care of children with spina bifida are able to provide
      information that is not available from other sources. CONCLUSIONS: This review
      provides a broad overview of many of the issues encountered during prenatal
      counseling sessions and emphasizes the additional value of the pediatric
      perspective during the process of informed decision making or preparation for an
      the birth of an affected child.

PMID- 17001679
TI  - Lessons learned from Art Pardee in cell cycle, science, and life.
AB  - This essay is written to honor Dr Art Pardee's 85th birthday (July 13, 2006). In
      this essay, I have summarized the lessons I learned from Art and the cell-cycle
      research I performed in Art's laboratory during my postdoctoral training period.
      I have also summarized some research from my own laboratory that has been
      inspired by the lessons I learned from Art, including the interactions between
      cell cycle and cell death regulators and discovery of novel polyphenol- and
      copper-based proteasome inhibitors. Finally, I have discussed the potential use
      of these proteasome inhibitors in cancer prevention and treatment.

PMID- 17001680
TI  - Galactosemia: the good, the bad, and the unknown.
AB  - Alpha-D-galactose is metabolized in species ranging from E. coli to mammals
      predominantly via a series of sequential reactions collectively known as the
      Leloir pathway. Deficiency of any one of these enzymes in humans results in a
      form of the inherited metabolic disorder, galactosemia, although the symptoms and
      severity depend upon the enzyme impaired, and the degree of functional deficiency
      (Tyfield and Walter, 2002, The Metabolic and Molecular Bases of Inherited
      Disease. New York: McGraw Hill.). Studies of these enzymes, and the disorders
      associated with their loss, have led to a much deeper appreciation of the
      intricate and interwoven levels of regulation that govern their normal function.
      These insights have further identified likely mediators of outcome severity in
      patients, and have enabled a rational approach to the development of novel
      strategies of intervention.

PMID- 17001681
TI  - An architectural perspective of cell-cycle control at the G1/S phase cell-cycle
      transition.
AB  - A prominent role for the execution of cell cycle and growth regulatory mechanisms
      within the three-dimensional context of nuclear architecture is becoming
      increasingly evident. Signaling pathways and regulatory networks that govern
      activation and suppression of genes controlling proliferation are functionally
      integrated for the organization and assembly of transcriptional machinery in
      nuclear microenvironments. The transcriptional activation of histone genes at the
      G1/S phase transition (S-point) is temporarily, functionally, and spatially
      distinct from transcriptional mechanisms at the restriction point (R-point). The
      spatial distinction in R-point versus S-point control is the localization of
      clustered histone gene loci at cajal bodies, which is modulated during the cell
      cycle. Histone nuclear factor P (HiNF-P), the principal factor mediating H4
      histone gene transcription, is the final link in the signaling cascade that is
      initiated with growth factor dependent induction of cyclin E/CDK2 kinase activity
      at the R-point and culminates in the NPAT-mediated activation of histone H4 genes
      through HiNF-P at the G1/S phase cell-cycle transition.

PMID- 17001682
TI  - The discovery of mRNA interferases: implication in bacterial physiology and
      application to biotechnology.
AB  - Escherichia coli contains a large number of suicide or toxin genes, whose
      expression leads to cell growth arrest and eventual cell death. This raises
      intriguing questions as to why E. coli contains so many toxin genes and what are
      their roles in bacterial physiology. Among these, MazF has been shown to be a
      sequence-specific endoribonuclease, which cleaves mRNAs at ACA sequences to
      completely inhibit protein synthesis. MazF is therefore called mRNA interferase.
      A number of other mRNA interferases with different cleavage specificities have
      been discovered not only in E. coli, but also in other bacteria including
      Mycobacterium tuberculosis. Induction of MazF in the cell leads to cellular
      dormancy termed quasi-dormancy. In spite of complete cell growth inhibition,
      cells in the quasi-dormant state are fully capable of energy metabolism, amino
      acids and nucleic acids biosynthesis and RNA and protein synthesis. The quasi
      dormancy may be implicated in cell survival under stress conditions and may play
      a major role in pathogenicity of M. tuberculosis. The quasi-dormant cells provide
      an intriguing novel biotechnological system producing only a protein of interest
      in a high yield. MazF causing Bak-dependent programmed cell death in mammalian
      cells may be used as a tool for gene therapy against cancer and AIDS. The
      discovery of a novel way to interfere with mRNA function by mRNA interferases
      opens a wide variety of avenues in basic as well as applied and clinical
      sciences.

PMID- 17001683
TI  - The deuterostome ancestor.
AB  - Hemichordates, the phylum of bilateral animals closest to chordates, can
      illuminate the evolutionary origins of various chordate traits to determine
      whether these were already present in a shared ancestor (the deuterostome
      ancestor) or were evolved within the chordate line. We find that an
      anteroposterior map of gene expression domains, representing 42 genes of neural
      patterning, is closely similar in hemichordates and chordates, though it is
      restricted to the neural ectoderm in chordates whereas in hemichordates, which
      have a diffuse nervous system, it encircles the whole body. This map allows an
      accurate alignment of the anterioposterior axes of members of the two groups. We
      propose that this map dates back at least to the deuterostome ancestor. The map
      of dorsoventral expression domains, organized along a Bmp-Chordin developmental
      axis, is also similar in the two groups in terms of many gene expression domains
      and for the placement of the gill slits, heart, and post-anal tail. The two
      groups, however, differ in two major respects along this axis. The nervous system
      and epidermis are not segregated into distinct territories in hemichordates, as
      they are in chordates, and furthermore, the mouth is on the Chordin side in
      hemichordates but the Bmp side in chordates. The dorsoventral dimension has
      undergone extensive modification in the chordate line, including centralization
      of the nervous system, segregation of epidermis, derivation of the notochord,
      perhaps from the gut midline, and relocation of the mouth. Based on the shared
      domain maps, speculations can be made for the remodeling of the body axis in the
      chordate line.

PMID- 17001684
TI  - Deregulation of cyclin E meets dysfunction in p53: closing the escape hatch on
      breast cancer.
AB  - In this review, we focus on pathways intersecting through p53 and cyclin E,
      highlighting how oncogenic effects of cyclin E deregulation, especially
      overexpression of shortened or low molecular weight (LMW) forms of cyclin E
      protein, are amplified by loss of regulatory control through p53 to promote tumor
      development. Expression of cyclin E protein promotes progression into S-phase, an
      activity opposed by p53-regulated activation of checkpoint controls or apoptosis.
      Loss of p53 function is an escape hatch by which tumor cells, initiated by a
      number of means including cyclin E deregulation, can avoid cell cycle arrest or
      cell death and progress through further stages of unchecked deregulation and
      growth. To determine how this escape hatch is opened and, ultimately, how to
      close it, we must understand the networks of normal signaling and processing in a
      cell and where they intersect.

PMID- 17001685
TI  - Therapeutic biology: checkpoint pathway activation therapy, HIV Tat, and
      transkingdom RNA interference.
AB  - Therapeutic biology is an exciting new frontier in the post-genomic era with the
      mission to better human health. The explosive increase in the understanding of
      molecular and regulatory biology has enabled the identification of a plethora of
      potential targets and pathways for the discovery of new medicines. Conversely,
      molecularly based therapeutic intervention of biological aberrations in human
      diseases offers a test of the depth of our understanding of biology. This article
      discusses three examples of therapeutic biology research. The first concerns the
      treatment of cancer by activating genome surveillance circuitry, namely
      checkpoint-pathway activation therapy. The second example is the identification
      of the HIV Tat protein as both a cause of immune cell activation and apoptosis,
      and as a vaccine candidate against HIV infection. The third example describes
      transkingdom RNA interference and its application in the investigational and
      therapeutic silencing of disease genes.

PMID- 17001686
TI  - Tracking the prevention of folic acid-preventable spina bifida and anencephaly.
AB  - BACKGROUND: The fortification of wheat flour with folic acid prevents most cases
      of spina bifida and anencephaly by raising serum folate levels among women
      capable of bearing children, as does encouraging women to consume folic acid
      supplements prior to pregnancy. Unfortunately, surveillance is conducted in few
      countries where the need is greatest. METHODS: A method for assessing the
      prevention of these birth defects is presented that combines fortification
      program information with country case prevalence estimates. RESULTS: This
      approach suggests that about 70% of all cases could be prevented within a year of
      implementation of fortification programs, were it not for the inertia of
      regulatory agencies. CONCLUSIONS: Professional researchers and clinicians can
      help combat this situation by becoming advocates for child health in their
      respective countries.

PMID- 17001689
TI  - Up-regulation of bone morphogenetic protein receptor IB by growth factors
      enhances BMP-2-induced human bone cell functions.
AB  - Bone morphogenetic proteins (BMP) stimulate osteoblast differentiation by signal
      transduction via three BMP receptors (BMPR-IA, -IB, and -II). Several growth
      factors, including transforming growth factor-beta1 (TGF-beta1), fibroblast
      growth factor-2 (FGF-2) and platelet-derived growth factor-AB (PDGF-AB), have
      also been shown to play an important part in osteogenesis. The mechanism
      underlying these activities is unclear, but these growth factors could modulate
      the BMP/BMPR pathway by up-regulating BMPR expression, thereby enhancing the
      osteogenic responses of bone cells to the BMP. In this study we have therefore
      examined the effects of TGF-beta1, FGF-2, and PDGF-AB on BMPR expression and BMP
      2-mediated osteoblast functions in primary human bone cells. The results showed
      that although the ligand BMP-2 and growth factors had little effect on BMPR-IA
      and -II transcript expression, they significantly up-regulated BMPR-IB mRNA
      specifically. However, only the growth factors, but not the ligand BMP-2,
      increased the surface expression of the BMPR-IB antigen, which was found to be
      due to a differential effect of BMP-2 and the growth factors on the Smurf1/Smad6
      induced breakdown process. Pre-incubation of the cells with the growth factors
      significantly augmented BMP-2-induced Smad1/5/8 phosphorylation, and Dlx5
      expression ALP activity, compared with that of cells treated with BMP-2 alone.
      When cells were transfected with siRNA targeting BMPR-IB, the growth factors
      neither up-regulated BMPR-IB transcript expression nor enhanced BMP-2-induced
      Smad1/5/8 phosphorylation, Dlx5 expression and ALP activity. The results indicate
      that increased BMPR-IB by TGF-beta1, FGF-2, and PDGF-AB significantly enhances
      BMP-2-induced osteogenic functions in vitro, suggesting that they might
      positively modulate bone formation by up-regulating BMPR-IB in vivo.

PMID- 17001690
TI  - A landscape of pinnacles: the extraordinary career of Arthur Pardee. A symposium
      to honor Dr. Arthur B. Pardee on his 85th birthday. June 2006, Boston,
      Massachusetts, USA.

PMID- 17001691
TI  - Tumor progression--targets for differential therapy.
AB  - Differential killing of the patient's cancer cells versus normal cells is a
      necessity for chemotherapy. Advantage can be taken of close regulations of gene
      expression and of enzyme activity that are essential for normal cell functioning,
      and that are altered during tumor progression. Summarized here is our research on
      four such progression changes of cancer cells; some deregulate proliferation
      control and others decrease programmed death (apoptosis). These processes will be
      illustrated with examples of potential chemotherapies based on them. Methods for
      discovery of such changes include Differential Display and microarrays.

PMID- 17001692
TI  - Cell senescence: hypertrophic arrest beyond the restriction point.
AB  - Withdrawal of mitogens (growth factors) arrests normal cells in G0 (quiescence).
      All other stresses and factors arrest cell cycle beyond the restriction point in
      G1 and G2 (non-G0 arrest), in the presence of mitogenic stimulation. Strong
      mitogenic stimuli by themselves cause non-G0 arrest. Unlike G0, arrest beyond
      restriction point is characterized by both high levels of cyclins and CDK
      inhibitors, activated mitogenic pathways with a secondary GF resistance, and
      continuous mass growth (cell hypertrophy). Prolonged hypertrophic arrest
      culminates in cell senescence. This review discusses that quiescence and
      senescence are two opposite, mutually exclusive conditions and that cell
      senescence can be reversed and prevented.

PMID- 17001693
TI  - Retinoid receptors, transporters, and metabolizers as therapeutic targets in late
      onset Alzheimer disease.
AB  - Vitamin A (retinoid) is required in the adult brain to enable cognition,
      learning, and memory. While brain levels of retinoid diminish over the course of
      normal ageing, retinoid deficit is greater in late onset Alzheimer disease (LOAD)
      brains than in normal-aged controls. This paper reviews recent evidence
      supporting these statements and further suggests that genes necessary for the
      synthesis, transport and function of retinoid to and within the ageing brain are
      appropriate targets for treatment of LOAD. These genes tend to be clustered with
      genes that have been proposed as candidates in LOAD, are found at chromosomal
      regions linked to LOAD, and suggest the possibility of an overall coordinated
      regulation. This phenomenon is termed Chromeron and is analogous to the operon
      mechanism observed in prokaryotes. Suggested treatment targets are the retinoic
      acid inactivating enzymes (CYP26)s, the retinol binding and transport proteins,
      retinol-binding protein (RBP)4 and transthyretin (TTR), and the retinoid
      receptors. TTR as a LOAD target is the subject of active investigation. The
      retinoid receptors and the retinoid-inactivating enzymes have previously been
      proposed as targets. This is the first report to suggest that RBP4 is an amenable
      treatment target in LOAD. RBP4 is elevated in type-2 diabetes and obesity,
      conditions associated with increased risk for LOAD. Fenretinide, a novel
      synthetic retinoic acid (RA) analog lowers RBP4 in glucose intolerant obese mice.
      The feasibility of using fenretinide either as an adjunct to present LOAD
      therapies, or on its own as an early prevention strategy should be determined.

PMID- 17001694
TI  - Mornings with Art, lessons learned: feedback regulation, restriction threshold
      biology, and redundancy govern molecular stress responses.
AB  - Work from the laboratory of Dr. Arthur B. Pardee has highlighted basic principles
      that govern cellular and molecular biological processes in living cells. Among
      the most important governing principles in cellular and molecular responses are:
      (i) threshold "restriction" responses, wherein a level of response is reached and
      a "point of no return" is achieved; (ii) feedback regulation; and (iii)
      redundancy. Lessons learned from the molecular biology of cellular stress
      responses in mammalian cancer versus normal cells after ionizing radiation (IR)
      or chemotherapeutic agent exposures reveal similar instances of these guiding
      principles in mammalian cells. Among these are the: (i) induction of cell death
      responses by beta-lapachone (beta-lap), a naphthoquinone anti-tumor agent that
      kills cancer cells via an NQO1 (i.e., X-ray-inducible protein-3, xip3)-dependent
      mechanism; (ii) induction of secretory clusterin (sCLU) in response to TGF-beta1
      exposure, and the ability of induced sCLU protein to down-regulate TGF-beta1
      signaling; and (iii) induction of DNA mismatch repair-dependent G(2) cell cycle
      checkpoint responses after exposure to alkylating agents. We have learned these
      lessons and now adopted strategies to exploit them for improved therapy. These
      examples will be discussed and compared to the pioneering findings of researchers
      in the Pardee laboratory over the years.

PMID- 17001695
TI  - Ronald J. Lemire: a man for the ages.

PMID- 17001696
TI  - Targeting histone deacetylases for the treatment of cancer and inflammatory
      diseases.
AB  - Histone deacetylases (HDACs) are involved in chromatin remodeling and
      modification of nonhistone transcription regulatory proteins, thus modulating the
      expression of genes important for complex biological events. Dysregulation of
      HDACs and aberrant chromatin acetylation and deacetylation may be implicated in
      the pathogenesis of various diseases, including cancer and inflammatory diseases.
      A significant number of HDAC inhibitors (HDIs) have been developed in the past
      decade. These inhibitors demonstrate strong anti-neoplastic effects in vitro and
      in vivo by inducing growth arrest, differentiation, and programmed cell death,
      inhibiting cell migration, invasion, and metastasis, and suppressing
      angiogenesis. More than a dozen HDIs are currently being evaluated in phase I-II
      clinical trials in patients with solid and hematological malignancies, and some
      have already shown promising activity with low toxicity. HDIs also exhibit strong
      anti-inflammatory effects in vitro and in animal models for various inflammatory
      diseases, thus representing a new class of promising agents for treating
      inflammatory diseases. This review provides an overview of HDACs in gene
      regulation, HDIs for cancer therapy and for potential treatment of inflammatory
      diseases, and future perspectives.

PMID- 17001697
TI  - Biological functions of maspin.
AB  - Maspin (Mammary Serine Protease Inhibitor) was first reported in 1994 as a serpin
      with tumor suppressive properties. Maspin was initially isolated through
      subtractive hybridization and differential display analysis as a 42-kDa protein
      that is expressed in normal mammary epithelial cells but reduced or absent in
      breast carcinomas (Zou et al., 1994). Further research led to maspin's
      characterization as a class II tumor suppressor based on its ability to inhibit
      cell invasion, promote apoptosis, and inhibit angiogenesis (Sheng et al., 1996;
      Zhang et al., 2000b; Jiang et al., 2002). Since then, efforts have been made to
      characterize maspin's tumor suppressive mechanisms. In particular, researchers
      have studied maspin localization, the regulation of maspin expression, and more
      recently, maspin protein interactions. By elucidating these mechanisms,
      researchers are beginning to understand the complex, pleiotropic nature of maspin
      and the pathways through which maspin exerts its tumor suppressive properties.
      These new findings not only further enhance our understanding of cancer biology
      but also provide an avenue to develop maspin's potential as a diagnostic marker
      for cancer progression, and as a potentially powerful therapeutic agent in the
      fight against breast cancer.

PMID- 17001698
TI  - Replitase: complete machinery for DNA synthesis.
AB  - Replication of nuclear DNA in eukaryotes presents a tremendous challenge, not
      only due to the size and complexity of the genome, but also because of the time
      constraint imposed by a limited duration of S phase during which the entire
      genome has to be duplicated accurately and only once per cell division cycle. A
      challenge of this magnitude can only be met by the close coupling of DNA
      precursor synthesis to replication. Prokaryotic systems provide evidence for
      multienzyme and multiprotein complexes involved in DNA precursor synthesis and
      DNA replication. In addition, fractionation of nuclear proteins from
      proliferating mammalian cells shows co-sedimentation of enzymes involved in DNA
      replication with those required for synthesis of deoxynucleoside triphosphates
      (dNTPs). Such complexes can be isolated only from cells that are in S phase, but
      not from cells in G(0)/G(1) phases of cell cycle. The kinetics of deoxynucleotide
      metabolism supporting DNA replication in intact and permeabilized cells reveals
      close coupling and allosteric interaction between the enzymes of dNTP synthesis
      and DNA replication. These interactions contribute to channeling and
      compartmentation of deoxynucleotides in the microvicinity of DNA replication. A
      multienzyme and multiprotein megacomplex with these unique properties is called
      "replitase." In this article, we summarize some of the relevant evidence to date
      that supports the concept of replitase in mammalian cells, which originated from
      the observations in Dr. Pardee's laboratory. In addition, we show that androgen
      receptor (AR), which plays a critical role in proliferation and viability of
      prostate cancer cells, is associated with replitase, and that identification of
      constituents of replitase in androgen-dependent versus androgen-independent
      prostate cancer cells may provide insights into androgen-regulated events that
      control proliferation of prostate cancer cells and potentially offer an effective
      strategy for the treatment of prostate cancer.

PMID- 17001699
TI  - Truncated RAR beta isoform enhances proliferation and retinoid resistance.
AB  - We previously reported the existence of a truncated isoform of the retinoic acid
      receptor beta, termed beta prime. Beta prime lacks the N-terminal domains of beta
      2 and beta 4, including the DNA-binding domain. However, beta prime is able to
      heterodimerize and interact with transcription cofactors. To determine the
      effects of different retinoic acid receptor isoforms on cell proliferation and
      apoptosis, we transduced retinoid sensitive (MCF7) and retinoid-resistant (MDA-MB
      231) cells with retinoic acid receptor beta 2, beta 4, or beta prime. Expression
      of the truncated beta prime isoform induces resistance to retinoic acid treatment
      in retinoid sensitive MCF7 cells. In both retinoid sensitive and resistant cells,
      expression of full-length beta 2 and beta 4 isoforms results in elevated
      sensitivity to retinoic acid treatment and caspase-independent cell death. Cell
      death in beta 4 transduced MDA-MB-231 cells was accompanied by metaphase
      chromosome decondensation and breakage suggestive of mitotic catastrophe. Our
      results provide evidence that: (a) the truncated form of the retinoic acid
      receptor beta induces retinoid resistance rather than sensitivity; and (b)
      alternative pathways of cell death are mediated by different isoforms in breast
      cancer cells.

PMID- 17001701
TI  - A pathological approach to anomalies of the posterior fossa.
AB  - BACKGROUND: Both clinical and postmortem diagnoses of posterior fossa anomalies
      remain difficult to make and to corroborate. This is particularly true for Dandy
      Walker malformation and variant. Difficulties arise for a variety of reasons,
      including technical and methodological ones, but also because the conditions may
      overlap anatomically with others, most notably mega cisterna magna, Blake's pouch
      cyst, and posterior fossa (arachnoid) cysts. Family counseling is difficult and
      complicated not only by diagnostic uncertainties but by the highly variable
      prognosis. METHODS: In this study, a systematic pathologic approach to study of
      the posterior fossa is put forth. The benefits of postmortem imaging and in situ
      and ex situ examination of posterior fossa contents are demonstrated. RESULTS:
      Normative data for cerebellar width (transverse cerebellar diameter) and height
      and vermian width and height are derived for the fetal period. These data will
      help workers recognize changes in these structures, particularly hypoplasia.
      CONCLUSIONS: Basic morphologic definitions of posterior fossa anomalies are
      advanced, in the hopes that better agreement can be reached between clinical and
      pathologic diagnoses and that better patient and family care will result.

PMID- 17001700
TI  - Holoprosencephaly: clinical, anatomic, and molecular dimensions.
AB  - Holoprosencephaly is addressed under the following headings: alobar, semilobar,
      and lobar holoprosencephaly; arrhinencephaly; agenesis of the corpus callosum;
      pituitary abnormalities; hindbrain abnormalities; syntelencephaly;
      aprosencephaly/atelencephaly; neural tube defects; facial anomalies; median cleft
      lip; minor facial anomalies; single maxillary central incisor; holoprosencephaly
      like phenotype; epidemiology; genetic causes of holoprosencephaly; teratogenic
      causes of holoprosencephaly; SHH mutations; ZIC2 mutations; SIX3 mutations; TGIF
      mutations; PTCH mutations; GLI2 mutations; FAST1 mutations; TDGF1 mutations; and
      DHCR7 mutations.

PMID- 17001702
TI  - Early studies of the nervous system by Ron Lemire.

PMID- 17001703
TI  - Evaluation of the cranial base in amnion rupture sequence involving the anterior
      neural tube: implications regarding recurrence risk.
AB  - BACKGROUND: Amniotic bands can cause disruption of the cranial end of the
      developing fetus, leading in some cases to a neural tube closure defect. Although
      recurrence for unaffected parents of an affected child with a defect in which the
      neural tube closed normally but was subsequently disrupted by amniotic bands is
      negligible; for a primary defect in closure of the neural tube to which amnion
      has subsequently adhered, recurrence risk is 1.7%. In that primary defects of
      neural tube closure are characterized by typical abnormalities of the base of the
      skull, evaluation of the cranial base in such fetuses provides an approach for
      making a distinction between these 2 mechanisms. This distinction has
      implications regarding recurrence risk. METHODS: The skull base of 2 fetuses with
      amnion rupture sequence involving the cranial end of the neural tube were
      compared to that of 1 fetus with anencephaly as well as that of a structurally
      normal fetus. The skulls were cleaned, fixed in 10% formalin, recleaned, and then
      exposed to 10% KOH solution. After washing and recleaning, the skulls were
      exposed to hydrogen peroxide for bleaching and photography. RESULTS: Despite
      involvement of the anterior neural tube in both fetuses with amnion rupture
      sequence, in Case 3 the cranial base was normal while in Case 4 the cranial base
      was similar to that seen in anencephaly. CONCLUSIONS: This technique provides a
      method for determining the developmental pathogenesis of anterior neural tube
      defects in cases of amnion rupture sequence. As such, it provides information
      that can be used to counsel parents of affected children with respect to
      recurrence risk.

PMID- 17001704
TI  - Mobilization of endothelial precursor cells: systemic vascular response to
      musculoskeletal trauma.
AB  - Postnatal vasculogenesis, the process by which vascular committed bone marrow
      stem cells or endothelial precursor cells (EPC) migrate, differentiate, and
      incorporate into the nacent endothelium contributing to physiological and
      pathological neovascularization, has stimulated much interest. Its contribution
      to tumor nonvascularization, wound healing, and revascularization associated with
      skeletal and cardiac muscles ischaemia is established. We evaluated the
      mobilization of EPCs in response to musculoskeletal trauma. Blood from patients
      (n = 15) following AO type 42a1 closed diaphyseal tibial fractures was analyzed
      for CD34 and AC133 cell surface marker expression. Immunomagnetically enriched
      CD34+ mononuclear cell (MNC(CD34+)) populations were cultured and examined for
      phenotypic and functional vascular endothelial differentiation. Circulating
      MNC(CD34+) levels increased sevenfold by day 3 postinjury. Circulating
      MNC(AC133+) increased 2.5-fold. Enriched MNC(CD34+) populations from day 3
      samples in culture exhibited cell cluster formation with sprouting spindles.
      These cells bound UEA-1 and incorporated fluorescent DiI-Ac-LDL intracellularily.
      Our findings suggest a systemic provascular response is initiated in response to
      musculoskeletal trauma. Its therapeutic manipulation may have implications for
      the potential enhancement of fracture healing.

PMID- 17001705
TI  - Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's
      sarcoma: bidirectional translational science.
AB  - Through the mentorship process, Dr. Arthur Pardee emphasized the critical
      importance of bidirectional translational research-not only advancing drug
      development from bench to bedside, but also bringing back precious clinical
      material to the laboratory to assess the biologic effects of therapeutic agents
      on their targets. This mini-review focuses on the signal transduction pathways of
      Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the
      rational development of molecularly targeted pathogenesis-driven therapies.
      Acquired immune deficiency syndrome (AIDS) related-KS results from co-infection
      with human immunodeficiency virus and KS herpesvirus/human herpesvirus-8
      (KSHV/HHV8), which leads to the development of an angiogenic-inflammatory state
      that is critical in the pathogenesis of KS. KS is driven by KSHV/HHV8-specific
      pathways, which include viral G protein-coupled receptor (vGPCR), viral
      interleukin-6 (vIL-6), and viral chemokine homologues. In addition, cellular
      growth/angiogenic pathways, such as vascular endothelial growth factor (VEGF),
      insulin-like growth factor, platelet-derived growth factor (PDGF), angiopoietin
      and matrix metalloproteinases (MMPs) are "pirated" by KSHV/HHV8. As a very
      tangible example of how translational research has led to a marked improvement in
      patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase
      inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors
      were serially biopsied. Not only did the patients' tumors regress, but also the
      regression was correlated with the inhibition of PDGF receptor (PDGFR) in the
      biopsy samples. Recent and future clinical trials of molecularly targeted therapy
      for the treatment of KS are a prelude to a shift in the paradigm of how KS is
      managed.

PMID- 17001706
TI  - Locally applied nerve growth factor enhances bone consolidation in a rabbit model
      of mandibular distraction osteogenesis.
AB  - Distraction osteogenesis is widely used in treating deformities, defects, and
      fractures of both long bones and craniofacial bones. Demands for acceleration of
      bone consolidation are increased in distraction osteogenesis. Nerve growth factor
      (NGF) can enhance innervation and bone regeneration in a fracture model and
      stimulate differentiation of osteoblastic cells. In this study, we tested the
      ability of locally applied NGF to enhance bone regeneration in a rabbit model of
      mandibular distraction osteogenesis. Twenty rabbits underwent bilateral
      distraction osteogenesis with a rate of 0.5 mm per 12 h. Two times 0.04 mg human
      NGFbeta (hNGFbeta) in buffer was injected into the callus after distraction. The
      contralateral side received placebo injections. Rabbits were euthanized at
      consolidation times of 14 and 28 days. Specimens were subjected to radiography,
      callus dimensions measurement, mechanical testing, and bone histological and
      histomorphometric analysis. The maximum load, bone volume/total volume, mineral
      apposition rate of the 1st to 11th day, and mineralized bone percentage were
      significantly higher in the hNGFbeta side at 14 and 28 days (p<0.05). The data
      indicate that locally applied hNGFbeta can accelerate callus maturation and may
      be an option to shorten the consolidation period in distraction osteogenesis.

PMID- 17001707
TI  - Biofilm formation by bacteria isolated from retrieved failed prosthetic hip
      implants in an in vitro model of hip arthroplasty antibiotic prophylaxis.
AB  - Bacterial infection primarily with Staphylococcus spp. and Propionibacterium
      acnes remains a significant complication following total hip replacement. In this
      in vitro study, we investigated the efficacy of gentamicin loading of bone cement
      and pre- and postoperative administration of cefuroxime in the prevention of
      biofilm formation by clinical isolates. High and low initial inocula,
      representative of the number of bacteria that may be present at the operative
      site as a result of overt infection and skin contamination, respectively, were
      used. When a high initial inoculum was used, gentamicin loading of the cement did
      not prevent biofilm formation by the 10 Staphylococcus spp. and the 10 P. acnes
      isolates tested. Similarly, the use of cefuroxime in the fluid phase with
      gentamicin-loaded cement did not prevent biofilm formation by four Staphylococcus
      spp. and four P. acnes isolates tested. However, when a low bacterial inoculum
      was used, a combination of both gentamicin-loaded cement and cefuroxime prevented
      biofilm formation by these eight isolates. Our results indicate that this
      antibiotic combination may protect against infection after intra-operative
      challenge with bacteria present in low numbers as a result of contamination from
      the skin but would not protect against bacteria present in high numbers as a
      result of overt infection of an existing implant.

PMID- 17001708
TI  - Biomechanical evaluation of a new augmentation method for enhanced screw fixation
      in osteoporotic proximal femoral fractures.
AB  - A biomechanical investigation on eight pairs of human cadaver proximal femurs was
      performed to evaluate the impact of a new augmentation method on the internal
      fixation of osteoporotic proximal femur fractures. The study focused on enhancing
      implant purchase to reduce the incidence of implant cut-out in osteoporotic bone.
      In a left-right comparison, a conventional hip screw fixation (control) was
      compared to the new cement augmentation method. After bone bed preparation
      through high pressure irrigation to remove fat, blood, and bone debris, the bones
      were augmented with low viscosity polymethylmethacrylate (PMMA) cement. Step-wise
      fatigue testing was performed by cyclically loading the femoral heads in a
      physiological manner, beginning at 1,500 N and increasing 500 N every 5,000
      cycles to 4,000 N, and continuously monitoring head displacement. Failure was
      defined as >5.0 mm head displacement. The head displacement at 2,000 N was
      significantly smaller (p=0.018) for the augmented group as compared to the
      conventionally treated bones (0.09+/-0.01 mm vs. 0.90+/-0.32 mm; mean+/-SEM). The
      displacement rate at the second load step was significantly higher (p=0.018) for
      the conventionally treated bones as compared to the augmented ones. All of the
      nonaugmented specimens failed during testing, where 50% of the augmented
      specimens did not fail. The promising results of these experiments suggest that
      this new standardized irrigation/augmentation method enhances the implant
      anchorage and offers a potential solution to the problem of implant cut-out in
      osteoporotic metaphyseal bone.

PMID- 17001709
TI  - Solvent-free asymmetric organocatalysis in a ball mill.

PMID- 17001710
TI  - Enantioselective ene reaction of cyclopentadiene and alpha,beta-enals catalyzed
      by a diphenylprolinol silyl ether.

PMID- 17001711
TI  - Mapping the fluorophilicity of a hydrophobic pocket: synthesis and biological
      evaluation of tricyclic thrombin inhibitors directing fluorinated alkyl groups
      into the p pocket.
AB  - In the completion of our fluorine scan of tricyclic inhibitors to map the
      fluorophilicity/fluorophobicity of the thrombin active site, a series of 11 new
      ligands featuring alkyl, alkenyl, and fluoroalkyl groups was prepared to explore
      fluorine effects on binding into the hydrophobic proximal (P) pocket, lined by
      Tyr 60A and Trp 60D, His 57, and Leu 99. The synthesis of the tricyclic scaffolds
      was based on the 1,3-dipolar cycloaddition of azomethine ylides, derived from L
      proline and 4-bromobenzaldehyde, with N-(4-fluorobenzyl)maleimide. Introduction
      of alkyl, alkenyl, and partially fluorinated alkyl residues was achieved upon
      substitution of a sulfonyl group by mixed Mg/Zn organometallics followed by
      oxidation/deoxyfluorination, as well as oxidation/reduction/deoxyfluorination
      sequences. In contrast, the incorporation of perfluoroalkyl groups required a
      stereoselective nucleophilic addition reaction at the "upper" carbonyl group of
      the tricycles, thereby yielding scaffolds with an additional OH, F, or OMe group,
      respectively. All newly prepared inhibitors showed potent biological activity,
      with inhibitory constants (K(i) values) in the range of 0.008-0.163 microM. The X
      ray crystal structure of a protein-ligand complex revealed the exact positioning
      of a difluoromethyl substituent in the tight P pocket. Fluorophilic
      characteristics are attributed to this hydrophobic pocket, although the potency
      of the inhibitors was found to be modulated by steric rather than electronic
      factors.

PMID- 17001712
TI  - Protein-structure-based prediction of animal model suitability for
      pharmacodynamic studies of subtype-selective estrogens.
AB  - Subtype-selective estrogens are of increasing importance as tools used to unravel
      physiological roles of the estrogen receptors, ERalpha and ERbeta, in various
      species. Although human ERalpha and ERbeta differ by only two amino acids within
      the binding pockets, we and others recently succeeded in generating subtype
      selective agonists. We have proposed that the selectivity of the steroidal
      compounds 16alpha-lactone-estradiol (16alpha-LE(2), hERalpha selective) and 8beta
      vinyl-estradiol (8beta-VE(2), hERbeta selective) is based on the interaction of
      certain substituents of these compounds with essentially one amino acid in the
      respective ER binding pockets. For in vitro and ex vivo pharmacological
      experiments with these compounds we intended to use bovine tissues available from
      slaughterhouses in larger quantities. Using homology modeling techniques we
      determined that the amino acid conferring high hERbeta-selectivity to 8beta-VE(2)
      is not exchanged between human and bovine ERalpha and bovine ERbeta. Thus, we
      predicted our steroidal hERbeta-selective compound to exhibit only weak agonistic
      activity at bERbeta and that bovine tissue is therefore not suited for
      investigation of ERbeta functions. The situation is presumably identical for pig,
      sheep, and the common marmoset, whereas rats, mice, and rhesus macaques are
      appropriate animal models to study pharmacological effects of 8beta-VE(2) in
      vivo. This prediction was confirmed in transactivation studies assessing
      estradiol (E(2)) and the two subtype-selective ligands on bovine ERbeta and on a
      series of hERalpha and hERbeta with mutations in their respective ligand-binding
      pockets. We have shown that the detailed understanding of the interactions of a
      compound with its target protein enables the identification of relevant species
      for pharmacological studies.

PMID- 17001713
TI  - Reversible binding of fluorescent proteins at DNA-gold nanoparticles.

PMID- 17001714
TI  - Main-chain bile acid based degradable elastomers synthesized by entropy-driven
      ring-opening metathesis polymerization.

PMID- 17001715
TI  - Secondary structure, dynamics, and topology of a seven-helix receptor in native
      membranes, studied by solid-state NMR spectroscopy.

PMID- 17001716
TI  - Useful reactions of silylated propargyltungsten or propargylmolybdenum species.

PMID- 17001717
TI  - "Sulflower": a new form of carbon sulfide.

PMID- 17001718
TI  - Cofabrication of electromagnets and microfluidic systems in
      poly(dimethylsiloxane).

PMID- 17001719
TI  - PdII-catalyzed aerobic allylic oxidative carbocyclization of allene-substituted
      olefins: immobilization of an oxygen-activating catalyst.

PMID- 17001720
TI  - Hydrogen storage in a highly porous solid derived from gamma-zirconium phosphate.

PMID- 17001721
TI  - Tissue imaging at atmospheric pressure using desorption electrospray ionization
      (DESI) mass spectrometry.

PMID- 17001722
TI  - A mononuclear alkylperoxocopper(II) complex as a reaction intermediate in the
      oxidation of the methyl group of the supporting ligand.

PMID- 17001723
TI  - SnIV complexes of N-confused porphyrins and oxoporphyrins--unique fluorescence
      "switch-on" halide receptors.

PMID- 17001724
TI  - Stereoselectivity and expanded substrate scope of an engineered PLP-dependent
      aldolase.

PMID- 17001725
TI  - Supramolecular receptor design: anion-triggered binding of C60.

PMID- 17001726
TI  - Efficient macrocyclization of preorganized palindromic oligosquaramides.

PMID- 17001727
TI  - Self-assembled vesicles from an amphiphilic ortho-phenylene ethynylene
      macrocycle.

PMID- 17001728
TI  - Ligand preorganization may be accompanied by entropic penalties in protein-ligand
      interactions.

PMID- 17001729
TI  - Electrical conformational bistability of dimesogen molecules with a molecular
      chord structure.

PMID- 17001730
TI  - Developments in Pd catalysis: synthesis of 1H-1,2,3-triazoles from sodium azide
      and alkenyl bromides.

PMID- 17001731
TI  - Colloidal crystal beads as supports for biomolecular screening.

PMID- 17001732
TI  - Highly reversible lithium storage in spheroidal carbon-coated silicon
      nanocomposites as anodes for lithium-ion batteries.

PMID- 17001733
TI  - Sequence-specific nucleic acid damage induced by peptide nucleic acid conjugates
      that can be enzyme-activated.

PMID- 17001734
TI  - Ion-transfer reactions at the nanoscopic water/n-octanol interface.

PMID- 17001735
TI  - A program for the visualisation, extraction, and reporting of NMR data from plate
      chemistry samples.
AB  - We describe a program for the viewing, analysis, and reporting of 1D NMR spectra.
      The program provides an intuitive environment to display 1D NMR spectra, and
      assists with data reduction and reporting. It is particularly well suited for
      multiple NMR spectra derived from the recording of spectra of samples in
      microtitre plates, where it adopts a unique, effective, and user-friendly
      approach. This also allows for quick overviews of the underlying NMR data and
      offers an effective tool for quality control in parallel chemistry.

PMID- 17001736
TI  - A conflation of existential and spiritual beliefs.

PMID- 17001737
TI  - Government health expenditures and health outcomes.
AB  - This paper provides econometric evidence linking a country's per capita
      government health expenditures and per capita income to two health outcomes:
      under-five mortality and maternal mortality. Using instrumental variables
      techniques (GMM-H2SL), we estimate the elasticity of these outcomes with respect
      to government health expenditures and income while treating both variables as
      endogenous. Consequently, our elasticity estimates are larger in magnitude than
      those reported in literature, which may be biased up. The elasticity of under
      five mortality with respect to government expenditures ranges from -0.25 to -0.42
      with a mean value of -0.33. For maternal mortality the elasticity ranges from 
      0.42 to -0.52 with a mean value of -0.50. For developing countries, our results
      imply that while economic growth is certainly an important contributor to health
      outcomes, government spending on health is just as important a factor.

PMID- 17001738
TI  - Re: Role of bladder neck mobility and urethral closure pressure in predicting
      outcome of tension-free vaginal tape (TVT) procedure.

PMID- 17001739
TI  - Naturally conceived twins with monochorionic placentation have the highest risk
      of fetal loss.
AB  - OBJECTIVE: The aim of this study was to estimate the rate of fetal loss in
      dichorionic (DC) and monochorionic (MC) twin pregnancies stratified according to
      zygosity and method of conception. METHODS: In a prospective multicenter
      observational study women with a twin pregnancy had an ultrasound scan before 14
      + 6 weeks' gestation in order to determine chorionicity. The fetal loss rate, the
      perinatal, neonatal and infant mortality rates and the frequency of very preterm
      labor were estimated for the different types of twin. RESULTS: Among the 495
      pregnancies (421 DC and 74 MC) 229 (46%) were conceived naturally and 266 (54%)
      by assisted reproduction (AR). Outcome data for 945 liveborn babies were
      obtained. The spontaneous miscarriage rate before 24 weeks' gestation was 10.9%
      (7/64) among naturally conceived MC compared to 3.0% (5/165) for naturally
      conceived DC twins (P < 0.05). For twins conceived by AR the corresponding
      figures were 0% (0/10) and 0.4% (1/256). The odds ratio (OR) for very preterm
      birth-before 28 weeks' gestation-was 4.2 for MC twins compared to DC twins. The
      relative risk of fetal loss or death among DC twins was 20% of the risk for MC
      twins. CONCLUSION: The risk of fetal loss, very preterm delivery and
      neonatal/infant death is significantly higher among twins with MC compared to DC
      placentation. Twins conceived by AR have a much lower risk of MC placentation.
      The risk of losing one or both twins seems higher among naturally conceived twins
      compared to twins conceived by AR, despite the fact that the maternal age was
      higher among the mothers of the AR twins.

PMID- 17001740
TI  - Direct analysis of hydrogen peroxide by capillary electrophoresis.
AB  - A method is described for analysis of hydrogen peroxide directly by CZE in borate
      buffer based on its absorption in UV light at 185 nm, without reaction with dyes.
      The absorption at 185 nm was about 3.5 times better than that at 214 nm. Hydrogen
      peroxide was generated enzymatically from glucose in aqueous solutions and in
      serum and was removed by the catalase enzyme. To improve the sensitivity of
      detection, samples were concentrated on the capillary based on stacking by ACN.
      The method is rapid (approximately 7 min) and specific.

PMID- 17001741
TI  - Atypical mobilities of single native DNA molecules in microchip electrophoresis
      revealed by differential interference contrast microscopy.
AB  - A transmitted-light optical microscope using differential interference contrast
      (DIC) was employed to follow the real-time dynamics of different kb-sized single
      native dsDNA molecules without fluorescent-dye labeling. In a PDMS/glass
      microchip, the electrophoretic migration velocities of large dsDNA molecules are
      lower than small dsDNA molecules in a running buffer of 0.25% v/v nonionic
      polymeric surfactant C16E6 (n-alkyl polyoxyethylene ether) in 100 mM N
      tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES) buffer because the
      C16E6 behaved as a dynamic polymer. However, the order of migration reversed in
      50 mM Gly-Gly buffer. The radial positions of individual DNA molecules (i.e.,
      center or walls of the microchip) did not change the migration order. The
      atypical migration order correlated well with the results in CE. The alignment of
      the deformable molecules due to viscous drag is likely responsible for these
      observations.

PMID- 17001742
TI  - A new method for fabrication of an integrated indium tin oxide electrode on
      electrophoresis microchips with amperometric detection and its application for
      determination of synephrine and hesperidin in pericarpium citri reticulatae.
AB  - A new, simple, and fast method to integrate indium tin oxide electrode in an
      amperometric detection (AD) microchip is introduced. Without the help of
      photoresist and complicated apparatus, the microchip could be fabricated in most
      laboratories in a very short time by this method. The experiment indicated that
      the microchip was stable and had good reproducibility. On this microchip, a new
      method was established to separate and determine synephrine and hesperidin, which
      are the main electroactively bioactive ingredients of pericarpium citri
      reticulatae, by AD. Under the optimal conditions, the two compounds could be
      completely separated within 5.5 min and the detection limits were 0.13 and 0.57
      microg/mL, respectively. The proposed method has been successfully used to
      determine synephrine and hesperidin in real pericarpium citri reticulatae sample,
      and the results show that the proposed method is sensitive, reliable, fast, and
      economical.

PMID- 17001743
TI  - Speciation of selenium compounds by open tubular capillary electrochromatography
      inductively coupled plasma mass spectrometry.
AB  - We introduce a T-type interface and a crossflow nebulizer to find ways to combine
      CEC with inductively coupled plasma MS (ICP-MS) detection for selenium
      speciation. For CEC separation, we employed a macrocyclic polyamine-bonded phase
      capillary as the separation column and a bare fused-silica capillary filled with
      the make-up liquid (0.05 M HNO3). The effect of nebulizer gas flow rate, make-up
      liquid flow, type, concentration and pH of the mobile phase on the separation
      have been studied. Tris buffer of 50 mM at pH 8.50 gave the best performance for
      selenium speciation. The reproducibility of the retention time indicated that
      sample injection by electrokinetic and nebulizer gas flow was better than that by
      self-aspiration alone. The detection limits for selenate, selenite, selenocystine
      and selenomethionine were found to be 2.40, 3.53, 12.86 and 11.25 ng/mL,
      respectively. Due to the high sensitivity and element-specific detection, as well
      as the high selectivity of the bonded phase, quantitative analysis of selenium
      speciation in urine was also achieved.

PMID- 17001744
TI  - Development and validation of a robust capillary electrophoresis method for
      impurity profiling of etomidate including the determination of chiral purity
      using a dual cyclodextrin system.
AB  - An enantioselective CE assay for the simultaneous determination of the
      enantiomeric purity and of related substances of etomidate has been developed and
      validated using a binary chiral selector system employing 30 mg/mL beta-CD and
      4.6 mg/mL sulfated-beta-CD in a 150 mM potassium phosphate buffer, pH 2.1. The
      method was validated with respect to specificity, range, linearity, LOQ and LOD,
      precision and accuracy. The assay allowed the detection and determination of
      related substances including (S)-etomidate at the 0.05% w/w level, the reporting
      threshold as defined by the International Conference on Harmonisation guidelines
      as well as the European Pharmacopoeia. Robustness testing was carried out by an
      "Augmented Plackett-Burman" design. Quantitation of the compounds was performed
      by calibration graphs with respect to lidocaine hydrochloride as internal
      standard and by peak area normalization, the procedure usually applied by
      pharmacopoeias. Although data obtained from the calibration graphs constructed
      with the aid of the internal standard were more accurate based on compound
      recovery, peak area normalization may also be used without significant loss of
      accuracy and precision.

PMID- 17001745
TI  - Why pelvic floor surgeons should utilize ultrasound imaging.

PMID- 17001746
TI  - Chorionicity and mode of fertilization: a long-standing misconception.

PMID- 17001747
TI  - In-utero pulmonary drainage in the management of primary hydrothorax and
      congenital cystic lung lesion: a systematic review.
AB  - OBJECTIVE: To determine the effect of in-utero pulmonary drainage on perinatal
      survival in fetuses with primary hydrothoraces and/or congenital cystic lung
      lesions. METHODS: Relevant papers were identified by searching MEDLINE (1966
      2004), EMBASE (1988-2004) and the Cochrane Library (2004 issue 2). Studies were
      selected if the effect of prenatal pulmonary drainage (shunt, surgery or
      drainage) on perinatal survival was compared with no treatment, in fetuses with
      ultrasonic evidence of lung pathology. Study selection, quality assessment and
      data abstraction were performed independently and in duplicate. RESULTS: Of a
      total number of 7958 articles, there were 16 controlled observational studies
      involving 608 fetuses. Study characteristics and quality were recorded for each
      study. Data were abstracted to generate 2 x 2 tables to compare the effect of
      pulmonary drainage vs. no drainage on perinatal survival. Pooled odds ratios
      (ORs) were used as summary measures of effect and the results were stratified
      according to predicted fetal prognoses. Pulmonary drainage did not improve
      perinatal survival in cystic lung lesions compared with no drainage (OR 0.56, 95%
      CI 0.32-0.97, P = 0.04) overall. However there was a marked improvement with this
      therapy in a subgroup of fetuses with fetal hydrops fetalis (OR 19.28, 95% CI
      3.67-101.27, P = 0.0005) but not in the subgroup uncomplicated by fetal hydrops
      fetalis (OR 0.04, 95% CI 0.01-0.32, P = 0.002). CONCLUSION: Percutaneous, in
      utero pulmonary drainage in fetuses with ultrasonic evidence of congenital
      pulmonary cystic malformations was associated with improved perinatal survival
      among fetuses with hydrops fetalis and therefore poor predicted survival.

PMID- 17001748
TI  - High perinatal survival in monoamniotic twins managed by prophylactic sulindac,
      intensive ultrasound surveillance, and Cesarean delivery at 32 weeks' gestation.
AB  - OBJECTIVES: Increased perinatal mortality in monoamniotic twin pregnancies is
      attributed to cord accidents in utero and at delivery. We evaluated the following
      parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement;
      (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie;
      and (3) the perinatal outcome with our current management paradigm. METHODS: This
      is a retrospective review of monoamniotic pregnancies of >or=20 weeks' gestation
      managed with serial ultrasound surveillance, medical amnioreduction and elective
      Cesarean delivery at 32 weeks' gestation. Mean amniotic fluid index (AFI) and
      change in AFI in monoamniotic pregnancies managed with oral sulindac was compared
      with 40 gestation-matched monochorionic-diamniotic controls. RESULTS: Among 44
      monoamniotic pregnancies, 20 with two live structurally normal twins at 20 weeks'
      gestation satisfied the inclusion criteria. All fetuses survived to 28 days
      postnatally despite early prenatal cord entanglement in all but one case. Whereas
      AFI remained stable throughout gestation in the controls, the AFI fell in those
      patients on sulindac from a mean value of 21.0 cm (95% CI, 18.5-23.6 cm) at 20
      weeks to a mean of 12.4 cm (95% CI, 10.1-14.6 cm) at 32 weeks (ANOVA P across
      gestation = 0.001) but mainly remained within normal limits. Fetal lie was
      stabilized in 11/20 cases in the monoamniotic group compared with 13/40 in the
      control group (P < 0.0001). CONCLUSIONS: Cord entanglement appears unpreventable,
      as it typically occurs in early pregnancy. Sulindac therapy reduces AFI, leads to
      more stable fetal lie, and may prevent intrauterine death by diminishing the risk
      of constricting cords that are already entangled. Perinatal survival in
      monoamniotic pregnancies managed by a regime of sulindac from 20 weeks'
      gestation, close ultrasound surveillance and elective abdominal delivery at 32
      weeks' gestation seems empirically higher than that in the literature.

PMID- 17001749
TI  - Comparison of alternative methods of collection of service use data for the
      economic evaluation of health care interventions.
AB  - Economic evaluation of health care interventions usually requires the collection
      of service use data to estimate the total cost of participants in an evaluation.
      There are a number of methods available to measure the quantity of services used
      but little is known about the relative accuracy of alternative methods. In a
      multicentre randomised controlled trial of interventions for the treatment of
      adults with recurrent episodes of deliberate self-harm (the POPMACT trial),
      health service data were collected by patient self-report after six and twelve
      months and also from GP records by independent investigators. Agreement for
      overall costs was relatively high. However, this hides substantial variation in
      agreement between the two sources of information for different services. The
      results suggest that GP records provide more accurate data on the use of general
      practice-based contacts than patient report, but less reliable information on
      contacts with other health services. Thus reliance on GP records for data on
      hospital services and other community health services based outside of general
      practice surgeries is not recommended. Future research should explore the level
      of agreement between patient report and other providing sector records, such as
      hospital records.

PMID- 17001750
TI  - Solution conformation of longifolene and its precursor by NMR and ab initio
      calculations.
AB  - We describe the conformation and stereospecific 1H and 13C chemical shift
      assignments of longifolene 1 and its penultimate precursor 2 through the combined
      use of ab initio calculations and experimental NMR techniques. The predicted
      stable conformation for both compounds was similar and adopts a twisted chair
      conformation at the seven-membered ring where C4 lies on top of the exocyclic
      double bond. The calculated chemical shifts for the stable conformation agree
      well with the experimental values.

PMID- 17001751
TI  - Structural determination of saponins from Hedysarum polybotrys.
AB  - Four saponins (1-4) were isolated from the roots of Hedysarum polybotrys Hand.
      Mazz. and obtained from Hedysarum (Tourn.) L for the first time. Their structures
      were identified on the basis of spectroscopic data. MS, 1D and 2D NMR including
      HMQC, HMBC, 1H-1H COSY and NOESY permitted correct assignments of all 1H and 13C
      signals of 1 and 2, and the 13C NMR data of 2 were reported for the first time.

PMID- 17001752
TI  - Synthesis and structure elucidation of five series of aminoflavones using 1D and
      2D NMR spectroscopy.
AB  - Twenty-six new aminoflavones have been synthesised by two different methods and
      the structure elucidation was accomplished using extensive 1D (1H, 13C) and 2D
      NMR spectroscopic studies (COSY, HSQC and HMBC experiments).

PMID- 17001753
TI  - Prenatal drug use and the production of infant health.
AB  - We estimate the effect of illicit drug use during pregnancy on two measures of
      poor infant health: low birth weight and abnormal infant health conditions. We
      use data from a national longitudinal study of urban parents that includes
      postpartum interviews with mothers, hospital medical record data on the mothers
      and their newborns, and information about the neighborhood in which the mother
      resides. We address the potential endogeneity of prenatal drug use. Depending on
      how prenatal drug use is measured, we find that it increases low birth weight by
      4-6 percentage points and that it increases the likelihood of an abnormal infant
      health condition by 7-12 percentage points.

PMID- 17001754
TI  - Maternal hemodynamic changes following treatment by laser coagulation of
      placental vascular anastomoses and amnioreduction in twin-to-twin transfusion
      syndrome.
AB  - OBJECTIVES: To investigate maternal hemodynamic changes following laser therapy
      and amnioreduction in twin-to-twin transfusion syndrome (TTTS). METHODS: Thirty
      nine cases with severe TTTS were treated at 16-26 weeks of gestation. Maternal
      hemodynamic evaluation was performed, including heart rate (HR), arterial
      pressure and echocardiography with calculation of shortening fraction (SF), left
      atrial dimensions, stroke volume (SV), cardiac output (CO) and total vascular
      resistance (TVR), before and 6 h and 24 h after placental surgery. Hemoglobin
      (Hb), hematocrit (Ht) and protein levels were also measured. Cases were
      retrospectively divided into groups according to treatment: Group A had laser
      therapy followed by amnioreduction >1000 mL (n = 25); Group B had laser therapy
      followed by amnioreduction <1000 mL (n = 14). RESULTS: The mean gestational age
      at inclusion was 21 (range, 16-26) weeks. The mean amniotic fluid withdrawal was
      1700 (range, 1000-3000) and 300 (range, 150-800) mL in Groups A and B,
      respectively. Cases in Group A showed a decrease in mean arterial blood pressure
      (P = 0.011) and in TVR (P < 0.0001) and an increase in CO (P = 0.008) and SV (P =
      0.022). There was no difference in HR. Significant hemodilution developed as
      early as 6 h after the procedure, with a reduction in Ht (P < 0.0001), plasma
      protein (P < 0.0001) and Hb levels of 1.2 g/dL on average (P < 0.0001). There
      were no changes in any parameters in Group B. CONCLUSIONS: Amnioreduction of
      severe polyhydramnios in TTTS induces maternal hemodynamic changes within the
      first 6 h that persist at least 24 h after treatment. These adaptative changes
      are compatible with hemodilution.

PMID- 17001755
TI  - Peripheral skin necrosis in the recipient of monochorionic twins complicated by
      twin-twin transfusion syndrome.
AB  - Twin-twin transfusion syndrome (TTTS) complicates approximately 15% of
      monochorionic, diamniotic twin pregnancies and if untreated carries a high
      perinatal loss rate of between 80% and 100%, depending on the stage. The
      underlying pathology in TTTS appears to be an imbalanced intertwin perfusion
      difference, secondary to functional unidirectional arteriovenous anastomoses
      within a monochorionic placenta. We report two cases of monochorionic twin
      pregnancy complicated by TTTS, in which the pregnancies were treated by serial
      aggressive amnioreduction. However, the recipient twin in each pregnancy
      developed 'ischemic damage' to a lower limb.

PMID- 17001756
TI  - Biometry of the pubovisceral muscle and levator hiatus in nulliparous Chinese
      women.
AB  - OBJECTIVES: To identify using three-dimensional (3D) ultrasound the morphological
      features and normal biometry of the levator hiatus in nulliparous Chinese women
      and to explore ethnic differences between these measurements and those in
      nulliparous Caucasian women. METHODS: 3D sonographic data from 59 nulliparous
      Chinese women (aged 19-38 years) who had no pelvic organ prolapse and no symptoms
      of pelvic floor dysfunction were retrieved from an image dataset and analyzed by
      offline post-processing. The pubovisceral muscle and levator hiatus were measured
      in the planes of maximal pubovisceral muscle thickness and minimum hiatal
      dimension, respectively. In addition, the genitohiatal and levator ani angles
      were measured. These values were compared with those in a published study of
      Caucasian women. RESULTS: In Chinese women there was no relationship between
      minimum anteroposterior (AP) hiatal diameter and minimum lateral hiatal diameter.
      Body weight was correlated with hiatal area and minimum AP hiatal diameter (r =
      0.391, P = 0.003 and r = 0.378, P = 0.004, respectively), whereas body mass index
      was correlated only with minimum AP hiatal diameter (r = 0.349, P = 0.008). There
      was a significant difference in average pubovisceral muscle thickness (P = 0.001)
      between nulliparous Chinese and Caucasian women. CONCLUSIONS: Body weight, body
      mass index, and ethnicity are factors affecting the biometry of the levator
      hiatus in Chinese nulliparous women.

PMID- 17001757
TI  - A modified stenting procedure for bile duct reconstruction.

PMID- 17001758
TI  - Another donor derived pathogen to watch out for.

PMID- 17001759
TI  - Hepatic arterial vasospasm early after liver transplantation?

PMID- 17001760
TI  - MCI is not a clinically useful concept.

PMID- 17001761
TI  - Patients with diabetes being undertreated for hypertension.

PMID- 17001762
TI  - ACE inhibitors may have chemoprotective effect.

PMID- 17001763
TI  - Virtual colonoscopy still misses small colorectal polyps.

PMID- 17001764
TI  - India's efforts to boost neonatal survival.

PMID- 17001765
TI  - New Orleans struggles to rebuild its health system.

PMID- 17001766
TI  - Regional variation is present in elbow capsules after injury.
AB  - Myofibroblast numbers and alpha-smooth muscle actin expression are increased in
      anterior joint capsules of patients with posttraumatic elbow contractures. The
      purpose of our study was to determine whether these changes occur regionally or
      throughout the entire joint capsule. We hypothesized that the alpha-smooth muscle
      actin mRNA expression and the myofibroblast numbers in posterior joint capsules
      would be elevated in elbows obtained from patients with posttraumatic joint
      contractures compared with joint capsules obtained from organ donor elbows
      without contractures. Semiquantitative reverse transcription-polymerase chain
      reaction was used to evaluate relative mRNA levels of alpha-smooth muscle actin.
      Glyceraldehyde-3-phosphate dehydrogenase was used to normalize the levels.
      Immunohistochemical analysis was used to determine the myofibroblast cell
      numbers. Higher alpha-smooth muscle actin mRNA levels were observed in elbows of
      patients with contractures compared with organ donor elbows without contractures.
      Immunohistochemical studies determined that myofibroblast numbers and the
      percentage of total cells that were myofibroblasts were elevated (2-2.5-fold) in
      the joint capsules from patients with posttraumatic joint contractures compared
      with similar tissue obtained from organ donor elbows without contractures. These
      results suggest elevated myofibroblast numbers occur throughout the whole joint
      capsule in posttraumatic elbow contractures, although there is some regional
      variation.

PMID- 17001767
TI  - Masters of efficiency.

PMID- 17001768
TI  - A bridge from Portugal to the States.

PMID- 17001769
TI  - Techniques of molecular oncology. Targeted gene replacement in mice.

PMID- 17001770
TI  - Essentials of modern immunology. How the immune system fights a viral infection.

PMID- 17001771
TI  - Haemostasis.
AB  - When the continuity of the vascular endothelium is disrupted, platelets and
      fibrin seal off the defect. Haemostatic processes are classified as primary
      (mainly involving platelets) and secondary (mainly related to fibrin formation or
      blood coagulation). When the blood clot is no longer required for haemostasis,
      the fibrinolytic system will dissolve it. The pivotal ligand for initial platelet
      recruitment to injured vessel wall components is von Willebrand factor (vWF), a
      multimeric protein present in the subendothelium and in plasma, where it is
      conformationally activated by shear forces. Adhering activated platelets recruit
      additional platelets, which are in turn activated and form a platelet aggregate.
      Coagulation is initiated by a reaction, activating factors IX and X. Once
      critical amounts of factor Xa are generated, thrombin generation is initiated and
      soluble fibrinogen is converted into insoluble fibrin. Excessive thrombin
      generation is prevented via inhibition by antithrombin and also via
      downregulation of its further generation by activation of the protein C pathway.
      Activation of the fibrinolytic system results from conversion of the proenzyme
      plasminogen into the active serine proteinase plasmin by tissue-type or urokinase
      type plasminogen activators. Plasmin digests the fibrin component of a blood
      clot. Inhibition of the fibrinolytic system occurs at the level of the
      plasminogen activator (by plasminogen activator inhibitors) or at the level of
      plasmin (by alpha2-antiplasmin). Together, these physiological processes act to
      maintain normal functioning blood vessels and a non-thrombotic state.

PMID- 17001772
TI  - Endothelial cell senescence.
AB  - The wear and tear processes that are thought to contribute to human ageing may
      play an important role in the development of vascular diseases. One such process
      is cellular senescence. In endothelial cells the senescent phenotype can be
      induced by a number of factors, including telomere damage, oxidative stress and
      sustained mitogenic stimulation. Several lines of evidence indicate that
      endothelial cell senescence maybe relevant to vascular disease. In this chapter
      we examine the causes, mechanisms and regulation of endothelial cell senescence
      as they emerge from studies in cell culture. We also describe the senescent
      phenotype and discuss its pathophysiological implications. We review the evidence
      for the occurrence of endothelial cell senescence in vivo and examine findings in
      animal models of ageing and human genetic disorders that argue for and against a
      role of endothelial cell senescence in age-related vascular pathology. Finally,
      we address the particular case of endothelial progenitor cell senescence and
      discuss the relevance of this phenomenon for angiogenesis and vascular repair.

PMID- 17001773
TI  - Primary care challenges in the management of respiratory tract infections.
AB  - Community-acquired respiratory tract infections (RTIs), such as community
      acquired pneumonia, acute exacerbations of chronic bronchitis, and acute
      rhinosinusitis, are among the most common reasons that adults seek care from
      their primary health care providers in the United States. High levels of
      pneumococcal resistance have developed, particularly to macrolides, since the
      1990s. Empiric management of these infections, the difficulty in differentiating
      bacterial from nonbacterial infection, and a high level of patient expectation of
      antimicrobial therapy contribute to the overuse of antibiotics. The primary care
      clinician must judiciously weigh various factors in order to prescribe
      appropriate and effective treatment.

PMID- 17001774
TI  - Some blood pressure pills may raise type 2 risk.

PMID- 17001775
TI  - Gastroparesis. A common stomach complication.

PMID- 17001776
TI  - How do I develop a good relationship with my doctor?

PMID- 17001777
TI  - Healthy eating. Healthy lunch box. Make the most of your mid-day meal.

PMID- 17001778
TI  - Stroke. Feared but preventable.

PMID- 17001779
TI  - Diabetes in the bedroom. Here's everything you've always wanted to know, but were
      embarrassed to ask.

PMID- 17001780
TI  - Rock 'n roll. Michael Ward has a Grammy, a bicycle he takes everywhere, and
      diabetes.

PMID- 17001781
TI  - Build your bones. People who have diabetes have a higher risk of bone density
      loss and fracture. Here's what you can do to keep your bones healthy and strong.

PMID- 17001782
TI  - Socks step out. New technology and choices give this neglected accessory a boost.

PMID- 17001783
TI  - Hot off the grill. Summertime sizzles in more ways than one.

PMID- 17001784
TI  - Research profile. Gene hunter. Kidney disease and diabetes. Johanna K. Wolford,
      PhD.

PMID- 17001785
TI  - Guidus n. gen. (Cestoda: Tetraphyllidea), with description of a new species and
      emendation of the generic diagnosis of Marsupiobothrium.
AB  - Guidus n. gen. (Cestoda, Tetraphyllidea) is proposed for 3 cestode species from
      skates (Bathyraja spp.: Rajiformes, Rajidae). Members of Guidus differ from those
      of all other phyllobothriid genera in possessing 4 sessile and conspicuously
      muscular, saclike bothridia; a bothridial aperture toward anterior end of scolex,
      and perpendicular to scolex axis; aperture surrounded by a continuous sphincter
      of circular muscles, and 1 marginal accessory sucker. A new species, Guidus
      argentinense n. sp., is described, the diagnosis of Marsupiobothrium antarcticum
      is emended, and it is transferred to the new genus along with Marsupiobothrium
      awii. These species can be easily distinguished from G. argentinense by the
      presence of lappets in the bothridial margin. In addition, the diagnosis of
      Marsupiobothrium is emended based on the redescription of the type species,
      Marsupiobothrium alopias.

PMID- 17001786
TI  - Description of a new diphyllidean parasite of triakid sharks from the deep Red
      Sea.
AB  - Specimens of Echinobothrium diamanti n. sp. (Cestoda: Diphyllidea) were recovered
      from the spiral intestine of Iago omanensis and Mustelus mosis
      (Carcharhiniformes: Triakidae), in the Gulf of Aqaba, Red Sea. The new species
      can be distinguished from all other species in Echinobothrium by the presence of
      a conspicuous vaginal sphincter. Echinobothrium diamanti possesses a corona of
      spines between the apical armature and the bothria, as in Echinobothrium
      notoguidoi, Echinobothrium musteli, and Echinobothrium scoliodoni, also parasites
      of sharks. However, E. diamanti possesses more testes per proglottid than E.
      notoguidoi and E. scoliodoni, and it is larger and has more spines per column on
      the cephalic peduncle than E. musteli and E. notoguidoi, and it also has circum
      medullary vitelline follicles rather than distributed in lateral columns.
      Echinobothrium diamanti is the first species of diphyllidean reported from the
      triakid genus Iago.

PMID- 17001787
TI  - Comments on "Comparison of in vitro and in vivo alpha/beta ratios for prostate
      cancer".

PMID- 17001788
TI  - Impact of a transfusion-free program on non-Jehovah's Witness patients undergoing
      liver transplantation.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is associated with a large
      amount of blood loss. This article examines the impact of the initiation of a
      transfusion-free program in January 2000 for Jehovah's Witnesses (JWs) on the
      overall use of blood products in non-JW patients undergoing OLT. DESIGN:
      Retrospective review of OLT from January 1997 through December 2004. SETTING:
      University of Southern California University Hospital. PATIENTS: A total of 272
      OLTs were performed on non-JW adults. This number includes 216 (79.4%) deceased
      donor and 56 (20.6%) living donor liver transplantations. Thirty-three OLTs were
      performed before January 2000 (ie, before the initiation of a transfusion-free
      program) (group 1), and 239 OLTs were performed after January 2000 (group 2). In
      group 2, all patients underwent OLT using cell-scavenging techniques and acute
      normovolemic hemodilution whenever feasible. Demographic, laboratory, and
      clinical data were collected and matched for severity of disease (model of end
      stage liver disease [MELD] score). Transfusion records of packed red blood cells
      (PRBCs), platelets, and fresh frozen plasma (FFP) were obtained from the
      University of Southern California blood bank. RESULTS: In comparing group 2 with
      group 1, the mean MELD score was statistically significantly higher (P < .001),
      whereas the mean number of intraoperative PRBC and FFP transfusions was
      significantly lower (P = .03 and P = .004, respectively). The number of
      preoperative and postoperative PRBC, FFP, and platelet transfusions between the 2
      groups was not statistically different. CONCLUSION: The development of a
      transfusion-free surgical program for JW patients has had a positive impact on
      reducing the overall blood use in non-JW patients undergoing OLT, despite the
      increase in MELD score.

PMID- 17001789
TI  - Bibliography. Current world literature. Prevention.

PMID- 17001790
TI  - A bitter pill for plaintiffs: obstacles to market theories of causation in
      prescription drug consumer fraud cases.

PMID- 17001791
TI  - Missouri State Medical Association 2006 member directory.

PMID- 17001792
TI  - [2006-2007 Nursing education and training guide].

PMID- 17001793
TI  - Approved: accreditation decision methodology refinements for the system
      accreditation option.

PMID- 17001794
TI  - ISEH 2006. Abstracts of the 35th Annual Scientific Meeting of the International
      Society for Experimental Hematology, Minneapolis, Minnesota, USA, September 27
      30, 2006.

PMID- 17001795
TI  - Cell injury: responses and repair. Proceedings of a seminar. March 31 and June 2,
      2004. Chicago, Illinois, USA.

PMID- 17001796
TI  - [XLII Congress of the Brazilian Society of Tropical Medicine, 4-8 March 2006,
      Teresina, Brazil].

PMID- 17001797
TI  - Abstracts of the Joint Annual Conference of the Swiss Society of Rheumatology and
      the Swiss Society of Physical Medicine and Rehabilitation, Geneva, Switzerland,
      September 28-29, 2006.

PMID- 17001798
TI  - The end of the beginning?

PMID- 17001799
TI  - Open-access chemistry databases evolving slowly but not surely.

PMID- 17001800
TI  - Pfizer hires 'outsider' for insider top job.

PMID- 17001801
TI  - An audience with... Robert R Ruffolo, Jr. Interview by Joanna Owens.

PMID- 17001802
TI  - Hepatitis C virus therapies.

PMID- 17001803
TI  - Dasatinib.

PMID- 17001804
TI  - Modification: appeal procedures that relate to the Review Hearing Panel report.

PMID- 17001805
TI  - Medicines, money and motivated health workers are key to universal access to
      HIV/AIDS prevention, treatment care and support.

PMID- 17001806
TI  - Young people and HIV: the evidence is clear - act now! Study identifies
      prevention interventions set to go!

PMID- 17001807
TI  - International patient safety goals created.

PMID- 17001808
TI  - Revision: definition of home medical equipment services.

PMID- 17001809
TI  - Re Elizabeth (Ross, Jones J.).

PMID- 17001810
TI  - [Key points in coronary endarterectomy].

PMID- 17001811
TI  - [Transplantation of the left lung].

PMID- 17001812
TI  - [Impact of the incidents at the Bristol Royal Infirmary].

PMID- 17001813
TI  - Who will lead academic CME?

PMID- 17001814
TI  - Neuroethical responsibilities.
AB  - Neuroscience represents a dynamic area of biomedical research where neuroethical
      responsibilities for researchers are emerging. This paper is the companion piece
      to the French-language one also published in this issue of the Canadian Journal
      of Neurological Sciences. It serves as a review of recent advances in neuroethics
      through the lens of three cases: (1) incidental finding of anomalies in
      neuroimaging research; (2) creation of neurotechnologies that can lead to
      cognitive enhancement, and (3) responsible communication of research results. We
      propose and discuss a multidimensional framework of neuroethical responsibilities
      to help tackle these issues. The framework reiterates the fundamental role of
      scientific integrity, puts in the foreground social responsibilities pertaining
      to the eventual use of neuroscience knowledge, and highlights self-reflection in
      research and training of researchers.

PMID- 17001815
TI  - Canadian Association of Neurosciences Review: polyglutamine expansion
      neurodegenerative diseases.
AB  - Since the early 1990s, DNA triplet repeat expansions have been found to be the
      cause in an ever increasing number of genetic neurologic diseases. A subset of
      this large family of genetic diseases has the expansion of a CAG DNA triplet in
      the open reading frame of a coding exon. The result of this DNA expansion is the
      expression of expanded glutamine amino acid repeat tracts in the affected
      proteins, leading to the term, Polyglutamine Diseases, which is applied to this
      sub-family of diseases. To date, nine distinct genes are known to be linked to
      polyglutamine diseases, including Huntington's disease, Machado-Joseph Disease
      and spinobulbar muscular atrophy or Kennedy's disease. Most of the polyglutamine
      diseases are characterized clinically as spinocerebellar ataxias. Here we discuss
      recent successes and advancements in polyglutamine disease research, comparing
      these different diseases with a common genetic flaw at the level of molecular
      biology and early drug design for a family of diseases where many new research
      tools for these genetic disorders have been developed. Polyglutamine disease
      research has successfully used interdisciplinary collaborative efforts,
      informative multiple mouse genetic models and advanced tools of pharmaceutical
      industry research to potentially serve as the prototype model of therapeutic
      research and development for rare neurodegenerative diseases.

PMID- 17001816
TI  - Propionibacterium acnes infections after cranial neurosurgery.
AB  - BACKGROUND: Propionibacterium acnes (P. acnes) is a relatively avirulent organism
      that is part of the normal skin flora. Most patient isolates are considered
      contaminants but, in a small subset of patients, particularly in the post
      neurosurgery setting, the organism can cause significant infections. We reviewed
      our experience with the occurrence and management of P. acnes infections after
      cranial neurosurgical procedures over a five-year period. METHODS: Patients with
      positive cultures for P. acnes between 1996 and 2001 were identified by review of
      the Saskatoon Health Region microbiology laboratory database. Of the 141 positive
      cultures, a review of hospital records identified six patients with P. acnes
      infections after neurosurgical procedures. A review of the literature related to
      P. acnes associated CNS infections was conducted. RESULTS: All patients had
      undergone a craniotomy or burrhole placement, and one patient had received prior
      radiotherapy. There were no P. acnes-related ventriculoperitoneal shunt
      infections. All patients presented with scalp swelling and three had purulent
      discharge. Symptoms occurred more than two months after the initial surgery in
      five of six patients, while one patient developed symptoms three years post
      operatively. Management for all patients included removal of the craniotomy flap
      and treatment with parenteral antibiotics, followed in most cases by oral
      antibiotics. A good response without relapse of infection was seen in five
      patients; one patient had recurrent infection after cranioplasty. CONCLUSIONS: P.
      acnes is a rare but important cause of infection after craniotomy. Wound
      debridement, removal of the bone flap and adequate antibiotic coverage result in
      cure in the majority of patients.

PMID- 17001817
TI  - Bilateral agenesis of the hippocampal dentate gyrus in a neurologically normal
      adult.
AB  - BACKGROUND: Ontogenic development of granule cells in the hippocampal dentate
      gyrus is influenced by genes including WNT3, EMX2, NEUROD, and LEF1. Dentate
      granule cells continue to be generated from stem cell precursors postnatally and
      during adult life, and are implicated in normal and abnormal neurological
      function. Developmental privation of dentate granule cells is rare and
      essentially always occurs in the context of other neurodevelopmental
      abnormalities. We have found no previous reports of severe, selective agenesis of
      dentate granule cells in humans. METHODS: A gross and microscopic examination of
      the brain included appropriate histochemical and immunohistochemical preparations
      and examination of the hippocampal formation at multiple levels bilaterally.
      RESULTS: This neurologically normal 82-year-old man was found to have bilateral
      agenesis of the hippocampal dentate gyrus, no identifiable dentate granule cells,
      and moderate disorganization of the pyramidal cell layer of Ammon's horn. We
      found no neurodevelopmental abnormalities outside the hippocampus. CONCLUSIONS:
      The hippocampal architectural alterations in this patient are similar to those
      associated with a murine Lef1 mutation, but our human case does not have the
      other congenital deficits reported in the Lef1-null mouse. Bilateral agenesis of
      the hippocampal dentate gyrus, and apparent failure of regeneration of dentate
      granule cells from stem cells in adult life, may occur without overt clinical
      neurological deficits.

PMID- 17001818
TI  - Rasmussen's encephalitis in a 58-year-old female: still a variant?
AB  - BACKGROUND: We report the case of a 58-year-old female with clinical,
      radiological, and histopathological evidence of Rasmussen's encephalitis,
      representing the oldest confirmed case to date. CASE SUMMARY: The patient
      presented with complex partial seizures characterized by numbness of the left
      face and staring spells. These progressed to a state of epilepsia partialis
      continua with jerking of the left face, as well as severe cognitive impairment
      and loss of all communication. The patient responded well to Intravenous
      Immunoglobulin (IVIG) therapy despite early complications and with ongoing
      treatment is living independently with minimal cognitive impairment. CONCLUSIONS:
      This represents the oldest confirmed case of Rasmussen's encephalitis and
      suggests that this diagnosis should be considered in patients of any age with an
      appropriate clinical picture. We recommend IVIG as a first line therapy for adult
      cases of Rasmussen's encephalitis.

PMID- 17001819
TI  - Intractable childhood epilepsy and maternal fatigue.
AB  - BACKGROUND: Mothers of children with intractable epilepsy are generally stressed
      and experience more emotional problems. Fatigue may affect their productivity,
      social interactions, and their ability to adequately take care of their children.
      The objectives were to examine the relationship between intractable childhood
      epilepsy and maternal fatigue, and explore possible contributing factors.
      METHODS: Sixty-four consecutive mothers of children with intractable epilepsy
      were identified prospectively. Exclusion criteria included degenerative/metabolic
      disorders or life threatening illness, such as brain tumors. Fatigue was measured
      using a standardized 11-item questionnaire, which has been revalidated in an
      Arabic speaking population. RESULTS: Mothers' ages were 24-45 years (mean 34) and
      ages of their epileptic children were 1-15 years (mean 6.7). Most children (64%)
      had epilepsy for >2 years, were on >1 antiepileptic drug (AED) (72%), and had
      daily seizures (47%). Thirty-four (54%) of the children had motor deficits and
      83% had mental retardation (severe in 41%). Twenty-eight (44%) mothers were
      fatigued. Factors associated with increased maternal fatigue included child's age
      <2 years (p=0.01), cryptogenic epilepsy (p=0.03), and severe motor deficits
      (p=0.04). Factors associated with lowered fatigue included performing regular
      exercise (p=0.006), lack of mental retardation (p=0.01), seizure control
      (p=0.05), using one AED (p=0.002), infrequent ER visits (p=0.005), and lack of
      recent hospitalization (p=0.005). CONCLUSIONS: Mothers of children with
      intractable epilepsy are increasingly fatigued. Several correlating factors were
      identified, mostly related to seizure control, mental and physical handicap.
      Strategies to manage the problem include proper education, seizure control,
      participation in regular exercise, social support, and psychological counseling.

PMID- 17001820
TI  - A novel GDAP1 mutation 439delA is associated with autosomal recessive CMT
      disease.
AB  - BACKGROUND: Charcot-Marie-Tooth (CMT) disease is the most common form of
      inherited motor and sensory neuropathy. Based on neurophysiological and
      neuropathological criteria CMT has been sub-classified into two main types:
      demyelinating and axonal. Furthermore, it is genetically heterogeneous with
      autosomal dominant, autosomal recessive (AR) and X-linked modes of inheritance.
      Thus far, seven genes have been identified in association with the demyelinating
      AR-CMT disease. We hereby report our clinical and molecular genetic findings in a
      consanguineous family with AR-CMT. METHODS: Two young sisters with AR-CMT and
      other non-affected family members were clinically and electrophysiologically
      evaluated and then molecular genetic investigation was carried out in order to
      identify the pathogenic mutation. RESULTS: Following an initial indication for
      linkage of the family to the CMT4A locus on chromosome 8, we sequenced the
      Ganglioside-induced differentiation-associated protein 1 (GDAP1) gene and
      identified a single nucleotide deletion in exon 3 that is associated with AR-CMT
      in the family. CONCLUSIONS: We identified a novel GDAP1 439delA mutation that is
      associated with AR-CMT in a consanguineous family of Iranian descent with two
      affected young girls and a history in other members of the family.

PMID- 17001821
TI  - Altered mental status and a retro-auricular mass.

PMID- 17001822
TI  - Unilateral hypoglossal nerve palsy following the use of the laryngeal mask
      airway.

PMID- 17001823
TI  - Occipital condyle fracture with associated hypoglossal nerve injury.

PMID- 17001824
TI  - Fibrous dysplasia of the skull base presenting acutely in an adult.

PMID- 17001825
TI  - Sepsis from neurofibromatosis.

PMID- 17001826
TI  - Pituitary carcinoma with subependymal spread.

PMID- 17001827
TI  - Lost fundamentals in neurosciences--a call for discussion.

PMID- 17001828
TI  - Tooth surface lesions: prevention and treatment--part II.

PMID- 17001829
TI  - Minimally invasive restorative dentistry: a biomimetic approach.
AB  - When providing dental treatment for a given patient, the practitioner should use
      a minimally invasive technique that conserves sound tooth structure as a clinical
      imperative. Biomimetics is a tenet that guides the author's practice and is
      generally described as the mimicking of natural life. This can be accomplished in
      many cases using contemporary composite resins and adhesive dental procedures.
      Both provide clinical benefits and support the biomimetic philosophy for
      treatment. This article illustrates a minimally invasive approach for the
      restoration of carious cervical defects created by poor hygiene exacerbated by
      the presence of orthodontic brackets.

PMID- 17001830
TI  - Primum non nocere: challenges in finding safe endodontic irrigants.

PMID- 17001831
TI  - Improving the standard of care using digital radiography: part I--implants and
      the general practitioner.

PMID- 17001832
TI  - Shade matching for a single tooth using an all-ceramic crown: laboratory
      protocol.

PMID- 17001833
TI  - Preservation of crestal bone: a clinical requisite.

PMID- 17001834
TI  - Current trends in gingival recession coverage--part I: the tunnel connective
      tissue graft.
AB  - The recession of the gingiva is increasingly becoming a more prominent condition
      in the oral health of many patients and should be treated at its earliest
      detection. The multifactorial etiology, decision modality, and current trends
      followed in the treatment of gingival recession are discussed in this
      presentation. The correction of Class I and II gingival recessions are presented
      as a means of minimizing surgical trauma and achieving predictable aesthetic
      results. Part II of this discussion will present alternative techniques in
      treating gingival recession.

PMID- 17001835
TI  - Achieving primary closure and enhancing aesthetics with periodontal microsurgery.
AB  - The continuous search for improved surgical procedures to address gingival
      deformities is a consequence of an increasing demand for aesthetics in the
      periodontal clinical practice. Innovative techniques have been reported to help
      clinicians achieve predictability in root coverage. Significant progress can be
      attributed to the inclusion of the operative microscope in periodontal therapy,
      particularly in regards to obtaining primary closure. This article describes a
      microsurgical technique used to treat gingival recessions, showing its potential
      for obtaining optimal aesthetic results.

PMID- 17001836
TI  - What can case managers do when they are not the ones controlling health benefits?

PMID- 17001837
TI  - A worksite diabetes prevention program: two-year impact on employee health.
AB  - The purpose of this study was to determine the 2-year impact of a worksite-based
      diabetes prevention program. Thirty-seven pre-diabetic and previously undiagnosed
      diabetic employees participating in a 12-month worksite diabetes prevention
      program were included. Weight, body mass index, waist circumference, oral glucose
      tolerance testing, fasting insulin, blood lipids, and aerobic fitness had
      improved significantly after 6 months. Much of this improvement continued through
      12 months. One year following the intervention, oral glucose tolerance and
      aerobic fitness had improved significantly. Of the 22 employees remaining in the
      study through 24 months, more than half had normal results on glucose tolerance
      testing. Worksite diabetes prevention programs may reduce blood glucose below pre
      diabetic and diabetic levels. Improvements in diabetes risk factors persisted for
      at least 2 years in most of these employees.

PMID- 17001838
TI  - Non-physical violence: a risk factor for physical violence in health care
      settings.
AB  - This research study assessed the extent to which non-physical violence is a risk
      factor for physical violence against workers in health care settings. More than
      600 nursing staff, other clinical providers, and non-clinical staff in two health
      care settings completed a cross-sectional survey. For the preceding 12-month
      period, 72.8% of workers reported at least one incident of non-physical violence
      and 21.3% reported at least one incident of physical violence. Workers who had
      experienced non-physical violence were 7.17 times more likely to experience
      physical violence than those who had not. Both patients and employees were
      perpetrators of non-physical and physical violence. These results indicate
      efforts to prevent or reduce physical violence against health care workers need
      to focus on non-physical as well as physical violence and employee as well as
      patient perpetrators.

PMID- 17001839
TI  - The skinny on weight-loss surgery: what occupational health nurses need to know.
AB  - Occupational health nurses are in a position to follow individuals undergoing
      bariatric surgery before and after the procedure. By fully understanding the
      health problems caused by obesity, occupational health nurses can effectively
      communicate the importance of diet and exercise.

PMID- 17001840
TI  - A place at the table.

PMID- 17001841
TI  - The functional capacity evaluation.

PMID- 17001842
TI  - [Antimicrobial susceptibility pattern of nosocomial gram negative pathogens:
      results from MYSTIC study in Hacettepe University Adult Hospital (2000-2004)].
AB  - Antimicrobial susceptibility patterns of Gram negative pathogens (n: 699)
      isolated from nosocomial infections in Hacettepe University Adult Hospital
      included in MYSTIC programme between 2000-2004 were determined by Etest (AB
      BIODISK, Solna, Sweden) using CLSI criteria. Of the total Escherichia coli (n:
      179), Klebsiella pneumoniae (n: 168), Pseudomonas aeruginosa (n: 179) and
      Acinetobacter baumannii (n: 173) isolates, 55% were from patients in inpatient
      clinics and 45% were from patients in intensive care units. The extended-spectrum
      beta-lactamase (ESBL) production rate of E. coli and K. pneumoniae isolates were
      28% and 47%, respectively. All E. coli and K. pneumoniae isolates were found
      susceptible to carbapenems. The susceptibility of ESBL positive E. coli isolates
      to piperacillin+tazobactam was 76% and 65% to cefepime, 63% to ceftazidime, 56%
      to tobramycin, 24% to ciprofloxacin. For ESBL negative E. coli isolates, the
      susceptibility rates were found 95%, 92%, 84% and 58% for ceftazidime and
      tobramycin, cefepime, piperacillin+tazobactam and ciprofloxacin, respectively.
      The susceptibility rates of ESBL positive K. pneumoniae isolates to
      piperacillin+tazobactam was 55% and 51% to cefepime, 49% to ciprofloxacin, 45% to
      tobramycin, 42% to ceftazidime. For ESBL negative K. pneumoniae isolates, the
      susceptibility rates were determined as follows; 92% for cefepime, 87% for
      tobramycin, 70% for piperacillin+tazobactam, 62% for ceftazidime and 60% for
      ciprofloxacin. Of the P. aeruginosa isolates, 77% were multi-drug resistant with
      susceptibility rates to piperacillin+tazobactam, ciprofloxacin, meropenem and
      imipenem as 55%, 53%, 51% and 49%, respectively. The susceptibilities of P.
      aeruginosa isolates were 48% to ceftazidime, 41% to cefepime and 35% to
      tobramycin. Of the A.baumannii isolates, 67% were multi-drug resistant with
      higher susceptibility rates to meropenem (53%), imipenem (48%) and tobramycin
      (44%) compared to other antimicrobials cefepime (37%), ciprofloxacin (29%),
      piperacillin+tazobactam (26%) and ceftazidime (22%).

PMID- 17001843
TI  - [Antimicrobial susceptibilities and serotype distribution of Streptococcus
      agalactiae strains isolated from pregnant women].
AB  - Streptococcus agalactiae (Group B streptococcus, GBS) is an important cause of
      neonatal morbidity and mortality. The aim of this study was to determine the
      serotype distribution and antibiotic susceptibility patterns of GBS isolated from
      pregnant women. A total of 671 pregnant women were screened for vaginal carriage
      of GBS, and vaginal colonization rate was found to be 14.6%. All GBS isolates
      were susceptible to penicillin, vancomycin, chloramphenicol and ofloxacin. The
      rates of GBS resistance to tetracycline, erythromycin and clindamycin were 81.6%,
      24.5% and 19.4%, respectively. The serotype distribution of GBS isolates was as
      follows in order of frequency; serotype III (33.7%), serotype Ib (24.5%),
      serotype V (18.4%), serotype Ia (7.1%), serotype IV (3.1%) and serotype II (2%).
      Eleven GBS isolates could not be serotyped by the antisera set used in the study.

PMID- 17001844
TI  - [Investigation of erythromycin resistance and resistance phenotypes in group A
      beta hemolytic streptococci].
AB  - Although penicillin resistance has not been determined in group A beta haemolytic
      streptococci (GABHS) yet, resistance to erythromycin and other macrolids is being
      reported frequently in the last years. In this study we investigated erythromycin
      resistance by using agar dilution method in 282 GABHS strains which were isolated
      from throat cultures that had been evaluated in the Ministry of Health, Ankara
      Training and Research Hospital's, Microbiology Laboratory. We also determined
      resistance phenotypes of resistant strains by double disc synergy method using
      erythromycin and clindamycin discs. Twelve of 282 strains (4.3%) were found
      resistant to erythromycin; five (41.7%) of which were M phenotype, four (33.3%)
      of which were constitutive type MLSB phenotype and three (25%) of which were
      inducible type MLSB phenotype. Investigation of resistance to macrolides that are
      alternatives to penicillin therapy in GABHS, is very important for the
      determination of the therapy and also to provide epidemiological data.

PMID- 17001845
TI  - [Antimicrobial susceptibility and serotype distribution of pneumococci strains
      isolated from meningitis patients].
AB  - Treatment of life threatening pneumococcal infections such as meningitis has
      recently become problematic due to the emergence of antibiotic resistant strains.
      Antimicrobial susceptibility data usually derived from the studies that included
      all clinical pneumococcal isolates. However, resistance patterns of this
      microorganism isolated from meningitis cases in our country are not exactly
      known. The aim of this study was to determine the antimicrobial susceptibility
      and serotypes of Streptococcus pneumoniae strains isolated from meningitis cases.
      This retrospective study was designed in three university hospitals in Turkey and
      72 pneumococci isolated from patients with meningitis were evaluated. In this
      study disk diffusion test and E-test methods were used to determine the
      susceptibility of pneumococci to some antibiotics. All S. pneumoniae isolates
      were serotyped using Quellung reaction. Although resistance for oxacillin was
      found by disc diffusion method in 11 isolates, only six of them were found to be
      resistant by E-test. By the latter procedure, no resistance was recorded against
      ceftriaxone and meropenem, while chloramphenicol resistance was found as 1.4%. In
      our study, erythromycin, ciprofloxacin and levofloxacin resistance were 2.8%, TMP
      SMX resistance was 26.4%, while no vancomycin resistance was detected by disk
      diffusion. In evaluation of 72 pneumococci, we found 16 different serotypes and
      four isolates could not be serotyped. The serogroup 23 (n: 19) was the most
      common one followed by serotype 19 (n: 9) and serotype 14 (n: 7). Of six
      resistant isolates, three pneumococci were serogroup 23 and the remaining were
      from three different serotype/serogroups 11, 14 and 19. As a result penicillin
      resistance in pneumococci isolated from meningitis was low and there was no
      resistance to ceftriaxone. It seems that ceftriaxone is an appropriate choice for
      empirical treatment of meningitis in our patients. These findings also revealed
      that pneumococcal polysaccharide capsule vaccines in use cover most of the
      invasive pneumococcal serotypes.

PMID- 17001846
TI  - [Antibiotic resistance in Streptococcus pneumoniae strains isolated from sterile
      body sites].
AB  - Antibiotic resistance in Streptococcus pneumoniae has become an important issue
      in the last years. Penicillin resistance rates vary among countries and among
      different regions in countries. It is important to know penicillin resistance
      rates among isolates, in planning empirical antimicrobial therapy in pneumococcal
      infections. In this study, the antibiotic resistance rates of S. pneumoniae
      strains isolated from sterile body sites were investigated with both E-test and
      disc diffusion methods for penicillin, erythromycin, levofloxacin, and with only
      disc diffusion method for chloramphenicol, ceftriaxone, vancomycin, rifampin,
      trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, and tetracycline. A total
      of 165 strains were included into the study of which 52 were isolated from blood,
      46 from cerebrospinal fluids, 25 from pleural fluids, 24 from dacryocystitis
      materials, 13 from tympanocentesis materials, 3 from joint fluids and 2 from
      wound specimens. Intermediate resistance to penicilin was 18.8%, while the
      resistance rates to TMP-SMX, tetracycline, chloramphenicol, erythromycin and
      levofloxacin were detected as 21.2%, 10.9%, 9.7%, 5.4% and 0.6%, respectively.
      None of the isolates were highly resistant to penicillin, nor resistant to
      vancomycin, ceftriaxone and rifampin. In conclusion, penicillin is still the
      first line therapeutic agent for pneumococcal infections except for severe
      infections such as meningitis, in our region.

PMID- 17001847
TI  - [Characterization of two new pigmented mycobacteria isolates].
AB  - Two pigmented mycobacteria isolated from sputum specimens were described by
      biochemical tests, whole-cell fatty acid analyses by High Performance Liquid
      Chromatography (HPLC) and sequencing of 65-kDa heat shock protein gene and 16S
      rRNA gene. The hsp65 gene and 16S rRNA gene sequences of the Mycobacterium sp.
      G1368 and Mycobacterium sp. E498 were deposited in DDBJ/EMBL/GenBank under
      accession numbers AY553874, DQ324791 and AY379074, DQ324792, respectively.
      Mycobacterium sp. G1368 grew in about one week at 37 degrees C and 42 degrees C
      and produced smooth, yellow colonies. It reduced tellurite and hydrolyzed urea.
      Nitrate reduction, aryl sulfatase, pyrazin amidase, heat stable catalase and
      semiquantitative catalase tests were also positive, while Tween 80 hydrolysis was
      weakly positive. Mycobacterium sp. E498 grew in about 9 days at 37 degrees C and
      formed smooth, yellow colonies. It hydrolyzed Tween 80, possessed aryl sulfatase,
      pyrazin amidase and heat stable catalase, however, it did not possess urease and
      nitrate reductase. These data, in addition to their position in the phylogenetic
      tree, strongly support the status of novel species at least for Mycobacterium sp.
      G1368.

PMID- 17001848
TI  - [Investigation of the bactericidal effect of urinary epithelial cells against
      different doses of Escherichia coli].
AB  - Epithelial cells take part in the stimulation of immune system during the
      conversion of nonspecific immune response to the adaptive one in the mucosal
      immune system. Epithelial cells also have critical roles in designating immune
      homeostasis towards immune regulation or tolerance. Its response type is
      determined according to the dose and structure of the antigen and the way it is
      presented. In this study, we aimed to evaluate the response of human urinary
      epithelial cells to different doses of Escherichia coli K12 by means of their
      bactericidal effect. Urine was collected from 16 healthy volunteers and urinary
      epithelial cells were prepared. The cells (effector) were stimulated with
      bacteria (target) in microplates for one hour with different effector/target cell
      ratios. At the end of the incubation period, the bactericidal effects were
      calculated and compared with microorganism controls. Mann-Whitney U test was used
      for statistical analysis. Urinary epithelial cells which were stimulated by E.
      coli K12 showed dose dependent bactericidal effect, calculated mean value for
      bactericidal effects were 60.7% at the 1/100.000 effector/target cell ratio and
      11.3% 1/1.000.000 effector/target cell ratio, indicating that the bactericidal
      effect was dose dependent.

PMID- 17001849
TI  - [Comparison of the diagnostic value of blood and bone marrow cultures in
      brucellosis].
AB  - The aim of this study was to compare the rates of brucellosis revealed by blood
      and bone marrow (BM) cultures obtained from patients followed up in our hospital,
      between 2002-2004 period. A total of 102 patients (62 male, 40 female; mean age:
      39 +/- 5 years) were included to the study and 61 of them were in acute, 29 were
      in subacute, and 12 were in chronic stages of brucellosis. Blood and BM samples
      collected from all of the hospitalized patients were cultured by using the BACTEC
      9050 system. The mean isolation period for BM cultures was 4.2 days, whereas it
      was 5.8 days for blood cultures. Overall the rate of positive blood cultures in
      brucellosis cases was found as 48% (n: 49), while the rate was was 34% (n: 35)
      for BM cultures, and the difference was statistically significant (p<0.05). Blood
      and BM culture positive results were detected in 40 (66%) and 28 (46%) of acute
      brucellosis cases, respectively. BM culture positive 23 samples yielded positive
      blood culture, while five were negative. These rates were found as 31% (n: 9),
      and 21% (n: 6) for subacute acute brucellosis cases, respectively. On the other
      hand Brucella spp. could not be isolated from blood cultures of 12 chronic cases,
      however, one (8%) was positive for BM culture. The patients were grouped
      according to their standard tube agglutination (STA) test results (group 1: 1/160
      1/640, group 2: 1/1280-1/2560 STA titers), and when comparing these groups for
      their positive blood and BM culture results, the high rate in group 2 was found
      statistically significant (p<0.05). Nineteen (70%) of 27 patients who had
      previously received specific brucellosis therapy were positive for blood and/or
      BM cultures, indicating insufficient use of antibiotics, or the use of
      inappropriate antibiotic combinations. It was concluded that, since the rate of
      positive blood cultures were low in especially chronic brucellosis cases, bone
      marrow cultures should be obtained for the definite evaluation of these patients.

PMID- 17001850
TI  - [Does pre-incubation period affect detection of Pseudomonas aeruginosa and
      Acinetobacter baumannii species with automatized BACTEC 9120 blood culture
      system?].
AB  - In this study, the effect of the pre-incubation period on detection of non
      fermentative species in blood culture system was investigated. Different
      concentrations of Pseudomonas aeruginosa and Acinetobacter strains were
      inoculated into BACTEC-9120 plus+Aerobic/F bottles and incubated for 0, 4, 8, 16
      hours at 36 dgerees C and then were loaded to the system. Both P. aeruginosa and
      A.baumannii strains yielded positive signals within 24 hours after loading. In
      all preincubation periods, as the concentration of P. aeruginosa strains
      decreased, the detection time was increased. The higher the concentration of
      A.baumannii strains, is the longer the signalling time as the pre-incubation
      period is increased, whereas the lower the concentration of A. baumannii strains,
      is the shorter the signalling time as the preincubation period is increased. Our
      study indicated that the BACTEC-9120 blood culture system determined non
      fermentative bacteria after a pre-incubation time of 16 hours.

PMID- 17001851
TI  - [Genotyping of hepatitis B virus by restriction enzyme analysis].
AB  - Hepatitis B is one of the most common infectious diseases in the world, and 350
      million people have been estimated to be chronic hepatitis B virus carriers world
      wide. Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H) based on
      an intergroup divergence of 8% or more in the complete nucleotide sequence.
      Different genotypes of the hepatitis B virus may influence the clinical outcome
      of the disease. HBV genotyping method using restriction fragment length
      polymorphism (RFLP) can reliably identify genotypes. HBV genotyping with S gene
      sequence is consistent with genetic analysis using the full genomic sequences.
      The aim of this study was to determine the genotypes of HBV by using restriction
      fragment length polymorphism (RFLP) method in the region of Elazig. A total of
      127 HBV-DNA positive patients (74 male, 53 female) were included in the study.
      Semi-nested polymerase chain reaction (PCR) was performed to amplify the specific
      parts of HBV S gene. In the first step, 685 base paired (bp) region was amplified
      by sense primer HBMF1 and anti-sense primer HBMR2, while in the second step 485
      bp region was amplified by using inner-sense primer HBMF2 and anti-sense primer
      HBMR2. PCR products were then digested by the restriction enzymes, Alwl, Earl,
      Hphl, Ncil and NlalV. The RFLP assay indicated that genotype D was the only
      detected type in our samples. In conclusion, genotype D is the predominant type
      among hepatitis B patients in our region. RFLP is considered to be an easy and
      useful method for genotyping HBV strains.

PMID- 17001852
TI  - [Investigation of some virulence factors of Trichosporon asahii strains isolated
      from the clinical samples of hospitalized patients].
AB  - In this study, acid proteinase, phospholipase and esterase activities, slime
      production and hydrophobic properties of a total of 48 Trichosporon asahii
      strains isolated from urine (43), peritoneal fluid (1), tongue swab sample (1),
      blood (1), nephrostomy (1) and one saprophyte strain from nail sample, were
      investigated. In none of the 48 strains, acid proteinase and phospholipase
      activities could be detected, while all were found to be esterase positive. In
      hydrocarbon assay performed with n-hexadecane, four strains exhibited moderate
      hydrophobicity, while 43 strains showed low level hydrophobicity and one strain
      was found to be negative. In the second procedure to measure hydrophobicity by
      using microspheres assay, the results were found to differ among the strains,
      with the lowest and the highest values between 53.2% and 92.7%. Establishing the
      production of slime, modified tube assay was performed. Ten strains were found to
      be moderate producers (++), 18 strains were weakly positive (+) and 20 strains
      were defined as non-slime producers. Since the current data on virulence factors
      of T. asahii is insufficient already, these results may contribute to the present
      data in the literature.

PMID- 17001853
TI  - [Malaria in Turkey and 14 years of clinical experience].
AB  - In this retrospective study, the epidemiologic and clinical characteristics of
      105 adult malaria patients, who had been hospitalized between the period of 1992
      and 2006 were evaluated. Nineteen percent of the patients were female, and the
      mean age was 28 +/- 10 years. Fifty percent of the patients acquired the
      infection in Southeastern Anatolia, while they were on military duty. The most
      common complaints were rigor (93%), fever (90%), sweating (90%), headache (76%),
      nausea (45%), and fatigue (38%). The most common physical examination findings
      were splenomegaly (86%) and hepatomegaly (62%). Anemia was detected in 23%,
      leukopenia in 47%, thrombocytopenia in 73%, two fold increase in ALT or AST
      enzyme levels in 32% of the patients. Plasmodium vivax was detected in 101 (96%)
      patients, whereas P. falciparum was detected in 4 patients (4%). Although the
      number of malaria cases in Turkey is declining in recent years, the febrile
      patients with a history of travel to the endemic regions should raise the
      suspicion of malaria.

PMID- 17001854
TI  - [Surveillance study of vancomycin resistant enterococci in pediatric haematology
      and oncology patients].
AB  - In this study, the prevalence and risk factors of fecal carriage of vancomycin
      resistant enterococci (VRE) among patients in Ondokuz Mayis University Pediatric
      Hematology and Oncology Clinics have been investigated. During two months, rectal
      swab samples were collected weekly from all of the patients hospitalized in
      Pediatric Hematology and Oncology Clinics, for the surveillance cultures. During
      the study a total of 85 rectal swabs were obtained from 34 patients who had been
      hospitalized in the inpatient clinic with 20 bed capacity. The number of samples
      obtained from the patients varied between 1-6 cultures. All of the patients
      (100%) had peripheral venous catheters and 27(79%) of patients had used
      antibiotics. All of the samples were inoculated onto 8 microg/ mL gentamicin
      containing blood agar media, and enterococci were identified by Gram staining,
      catalase test and at species level by VITEK 2 (bioMerieux, France) automated
      system. Vancomycin resistance was screened by using 6 microg/mL vancomycin
      containing brain-heart infusion agar according to CLSI guidelines. The vancomycin
      MIC values of the strains grown in this medium were determined by microdilution
      test proposed by CLSI. As a result, a total of 50 samples (59%) belonging to 24
      patients yielded enterococci, and the species distribution was as follows; E.
      faecium (in 16 cases), E. faecalis (in 8 cases), E. casseliflavus (in 6 cases),
      E. avium (in 3 cases) and E. durans (in 1 case). In our study no vancomycin
      resistance nor VRE colonization was detected in the patients.

PMID- 17001855
TI  - [Investigation of serum resistance for Pseudomonas aeruginosa and Acinetobacter
      baumannii strains].
AB  - Serum resistance is one of the major virulence factors of Gram negative bacteria.
      The aim of this study was to investigate the serum resistance of Pseudomonas
      aeruginosa and Acinetobacter baumannii strains isolated from various clinical
      samples (19 tracheal aspirates, 14 urine, 7 sputum, 7 wound and one peritoneal
      fluid specimens). Forty-eight P. aeuginosa and 48 A. baumannii strains were
      tested for human serum bactericidal effect by using Benge's method. Thirty-five
      (72.9%), 9 (18.7%), and 4 (8.3%) of P. aeruginosa strains were found to be
      resistant, intermediate sensitive and sensitive to serum, respectively. These
      rates were detected as 81.2% (39/48), 14.5% (7/48), and 4.1% (2/48) for A.
      baumannii strains, respectively. It can be concluded that, high serum resistance
      rates of P. aeruginosa and A. baumannii isolates might have an important role in
      the pathogenesis of infections of these bacteria.

PMID- 17001856
TI  - [Evaluation of brucellosis patients in Trakya University Hospital].
AB  - Human brucellosis is an endemo-epidemic disease in the Trakya Region of Turkey.
      The aim of this retrospective study was to evaluate the clinical, laboratory
      findings, therapeutic features, and prognosis of the 47 patients (49% were
      female, age range: 17-76 years, mean age: 45 years) with human brucellosis
      followed up in Trakya University Hospital between 2001-2005. The patients were
      categorized as acute (64%), subacute (28%) and chronic (9%) brucellosis.
      Complications were detected in 51% of the patients and spondylodiscitis was the
      most common (30%) complication. Twenty-seven percent of patients with
      spondylodiscitis were classified as acute, 46% were subacute, and 27% were
      chronic brucellosis. Other complications were sacroileitis (9%), arthritis (4%),
      meningitis (4%), endocarditis (2%), and orchitis (2%). Positive blood cultures
      were detected in 80% and 54% of acute and subacute cases, respectively, however,
      blood cultures were all negative in the chronic cases. Overall positive blood
      cultures were observed in 68% of cases. Fifty-one percent of the patients were
      treated with doxycycline+streptomycin, and 40% with doxycycline+rifampicin. Two
      patients with meningitis were treated with doxycycline+rifampicin+ceftriaxone,
      and one patient with endocarditis was treated with
      doxycycline+rifampicin+cotrimoxazole combinations. Relapse was observed in two
      (4%) of the patients. Since serious complications were observed in half of the
      brucellosis patients, combination therapies were prolonged. Complete evaluation
      of patients with human brucellosis requires investigation of osteoartricular
      complications and modification of the duration of therapy according to the
      existing complication.

PMID- 17001857
TI  - [E-test susceptibility results of brucella strains for streptomycin, rifampicin,
      ciprofloxacin and tetracycline].
AB  - Although Brucella species are susceptible to many antimicrobial agents in vitro,
      the susceptibility tests for these bacteria are not well standardized and the
      break point values are not described yet clearly. The aim of this study was to
      investigate the minimum inhibitory concentration (MIC) values of 43 Brucella
      strains isolated from blood cultures by E-test. Streptomycin and rifampicin E
      tests were performed for all of the strains, however, tetracycline and
      ciprofloxacin were tested for only 27 and 17 strains, respectively. The MIC
      interval for streptomycin was 0.025-1 mg/L, for rifampicin 0.19-1.5 mg/L, for
      tetracycline <0.016-0.032 mg/L, and for ciprofloxacin 0.094-0.64 mg/L. One strain
      was found intermediately susceptible to rifampicin. In may be concluded that
      development of resistance is not eligible against antibiotics which are currently
      used for brucellosis therapy.

PMID- 17001858
TI  - [Investigation of autoantibody, anti-HCV and anti-HIV seropositivities in "anti
      HBc alone" positive samples].
AB  - "Anti-HBc alone" which is an unusual serologic pattern of hepatitis B virus (HBV)
      infections, may be detected in the seropositive samples for hepatitis C virus
      (HCV), human immunodeficiency virus (HIV) infections and in the presence of
      autoantibodies due to cross reactions. In this study, 20 serum samples with
      isolated antibody to hepatitis B core antigen, which were detected in May 2005,
      have been investigated by means of the presence of some autoantibodies (anti
      nuclear antibody; ANA and rheumatoid factor; RF), anti-HCV and anti-HIV, in the
      Central Laboratory of Dicle University Medical School. All of the "anti-HBc
      alone" samples were negative for HBV-DNA by real-time polymerase chain reaction
      (PCR), and liver enzyme (ALT and AST) levels were normal except for three
      patients. As a result, a total of six (30%) samples were found positive. Four of
      them were positive for ANA and two were positive for anti-HCV, while one serum
      yielded positivity for both ANA and anti-HCV. Anti-HCV positive samples were
      searched for the presence of HCV-RNA by real-time PCR, and none were found
      positive. Of three patients with increased AST and ALT levels, one was anti-HCV
      positive, one was ANA positive, while the other was negative for all parameters.
      In conclusion, possible presence of autoantibodies and anti-HCV should be taken
      into consideration during the evaluation of isolated anti-HBc IgG positive test
      results.

PMID- 17001859
TI  - [A case of brucellosis presenting with urinary tract infection].
AB  - In this report an acute brucellosis case presenting with the symptoms of urinary
      tract infection (UTI) has been discussed. A 29 years old male patient was
      admitted to the emergency service of our hospital with the complaints of acute
      UTI. His complaints were persisting for five days before admission. His physical
      examination was normal but there were fever (39 degrees C) and costovertebral
      angle tenderness. His medical history revealed that multiple stones in the lower
      pole of the right kidney and paranchyme loss were detected by IVP two years ago.
      The bacteria that were isolated from blood and urine cultures were identified as
      Brucella melitensis by conventional methods. Rose Bengal test was found positive,
      and standard tube agglutination test was positive at a titer of 1/640. The
      patient was treated with oral ciprofloxacin (1000 mg/day) and rifampicin (600
      mg/day) combination for six weeks. The aim of this presentation was to draw
      attention to this uncommon condition, as UTI symptoms are not the first symptoms
      of acute brucellosis. UTI symptoms should be carefully considered as a
      presentation of brucellosis especially in regions where brucellosis is endemic.

PMID- 17001860
TI  - [Crimean-Congo Hemorrhagic Fever].
AB  - Crimean-Congo Hemorrhagic Fever (CCHF) virus is a tick-borne virus, which is a
      member of Bunyaviridae family, Nairovirus genus. CCHF virus has been isolated
      from 31 different tick species so far, and genus Hyalomma includes the basic
      vectors of which H. anatolicum, H. marginatum, H. detritum, H. dromedarii, H.
      excavatum and H. turanicum are frequently found in the geography in which Turkey
      takes place. The virus is transmitted via the bite of infected ticks or direct
      contact with CCHF infected patients and the products of infected animals.
      Following 2-9 days incubation period, the disease abruptly starts with fever,
      feeling cold, shivering, headache, muscle and joint aches. After a few days
      hemorrhage develops at various parts of the body. Since an effective vaccine and
      a specific antiviral therapy have not been found yet, the high mortality rate
      which may reach to 10-60%, and a wide geography affecting approximately 40
      countries including Turkey, CCHF attracts the attention of both scientific and
      mediatic world, in recent years. In this article, the structure, vectors and
      reservoirs of CCHF virus, together with the epidemiology, clinical features,
      laboratory diagnosis and strategies of treatment and prevention, have been
      reviewed.

PMID- 17001861
TI  - [Retrospective evaluation of brucellosis cases inhabiting in Mus province].
AB  - The aim of this study was to evaluate the brucellosis patients inhabiting in Mus
      province, in Eastern Anatolia of Turkey, retrospectively. The mean age of the
      patients (n: 87) was 38.1 +/- 12.4 years, and 45% of them were female. The
      transmission route was the consumption of unpasteurized fresh cheese (in 85%),
      and unboiled milk (in 45%). The most common symptoms were recorded as chills
      (89%), fever (87%), and arthralgia (81%). Splenomegaly (71%) and hepatomegaly
      (63%) were the predominant physical examination signs. Diagnosis was made based
      on the clinical features and positive Rose-Bengal test result (93%), however,
      blood cultures could not be performed due to insufficient laboratory equipment.
      In 92% of the patients at least one complication has been detected indicating
      delayed admission to the hospital, while the most common complications were
      sacroileitis (79%) and spondylitis (44%). Streptomycin+doxycyclin,
      streptomycin+doxycyclin+ ciprofloxacin, and streptomycin+doxycyclin+ rifampicin
      combination therapies were used in 62%, 24% and 14% of the patients,
      respectively, for six weeks, resulting with complete cure.

PMID- 17001862
TI  - [Origins of French telemedicine legislation].
AB  - After the creation of the european institute of telemedicine on 10 July 1989 at
      Paul Sabatier university in Toulouse, it became clear that legislation was needed
      to provide a solid framework for this new medical practice. The French
      government's decision in 1993 to create an experimental telemedicine network in
      the Midi-Pyrenees region, bringing together all public and private healthcare
      establishments, led us to manage telemedicine in much the same way as a hospital
      department. This resulted in the creation of institutional systems suited to
      multicenter networking and requiring particular regulations to govern healthcare
      professionals' responsibilities, financing, data security, and the use of new
      communication and information technologies. Articles specific to telemedicine
      were integrated into the law of 13 August 2004 relating to the reorganisation of
      French healthcare insurance.

PMID- 17001863
TI  - [Teledermatology in Midi-Pyrenees].
AB  - Telemedicine has become commonplace since the creation of the European Center of
      Telemedicine, and dermatology was a pioneering discipline in this new technology.
      The Division of Dermatology is now involved at three different levels--The Midi
      Pyrenees regional network, which allows doctors in the private and public sectors
      to seek expert advice, in real time, from university hospital specialists.--He
      Division of Dermatology pioneered telemedicine sessions devoted to file review,
      histological/clinical diagnosis, and information exchanges among subspecialists
      in dermatology. Both French and foreign specialists attend these sessions.-
      Teaching, particularly for students and private practitioners. Telemedicine has
      clear benefits for patients, doctors and society as a whole. The private and
      hospital community of the Midi-Pyrenees region is constantly seeking to improve
      its health services, and ensures that all new approaches are subject to strict
      quality controls.

PMID- 17001864
TI  - [Military telemedicine: a network of networks].
AB  - Military telemedicine is a form of collaborative medicine based on the use of
      communication and information networks. It is more a network of networks than of
      independent systems. It comprises electronic medical files, epidemiological
      networks, and surgical and medical databases. Each system must be able to
      communicate with the others, thereby enabling the development of remote
      consultation, expertise and assistance. This requires networking between the
      army, the navy, and the air force communication networks, especially during
      special operations conducted abroad. We must also develop interoperability with
      systems in other countries, and with the French civilian health service. This
      means respecting the general rules governing these networks. The military health
      network is unique, in that it focuses on battlefield injuries. In addition, the
      French military health service operates under a single headquarters, governing
      nurses, paramedics and physicians.

PMID- 17001865
TI  - [The TELIF network of Paris-area public hospitals (AP-HP)].
AB  - After a feasibility study, the TELIF network (neurosurgical emergencies in the
      Paris region) was created in November 1994. The goal was to reduce the number of
      patient transfers among the different hospitals, by teletransmission of computed
      tomography images between computers located in the emergency departments of
      general hospitals and the neurosurgery department. The initial goal has been
      reached, with a 70 % reduction in the number of patient transfers. The network is
      also being used with success for teleinterpretation of standard radiographs in
      gerontology. Today the network's technology is obsolete, and it will now be
      integrated into the new medical record system, using web-based technology for
      secure and confidential teletransmission.

PMID- 17001866
TI  - [Responsibility in telemedicine].
AB  - Telemedicine networks raise a number of legal issues that concern patients,
      health professionals and data managers alike. Patients must be informed, and, in
      France, can freely choose the persons who treat them. Individual patients'
      healthcare information must be kept strictly confidential. All healthcare
      professionals have a right to equal consideration, and must retain their
      independence within the network. Their responsibility can be engaged, and this
      calls for specific guidelines. The data manager is a new actor in the healthcare
      system. Whether an individual or an organization, the data manager must store
      sensitive information in precise conditions.

PMID- 17001867
TI  - [Economic aspects of telemedicine].
AB  - The aim of health technology assessments is to study the incremental impact of
      health interventions within a complex care system characterised by a multitude of
      individual behaviours and institutions. Most frameworks available for
      telemedicine evaluation simply examine financial costs relative to face-to-face
      consultations. Current data collection systems are poorly suited to rigorous
      analyses of new networks in everyday situations. Randomised trials are designed
      to remove sources of interference that could mask a causal relationship between a
      new organization and a set of results. Their methodology, which introduces the
      term ceteris paribus into the principles of good practice, is poorly suited to
      analyzing individual behaviours. Observational studies attempt to describe actual
      treatment situations as accurately as possible. By definition, however, they
      assume that the natural course of events is not deviated by interventions. The
      absence of an experimental plan increases the likelihood of bias and makes it
      more difficult to test for causal relationships. These approaches are poorly
      suited to testing for incremental effectiveness. Quasi-experimental studies and a
      staged approach would be more suited to a comprehensive assessment of
      telemedicine initiatives. In this way its impact on effectiveness, integration of
      care, quality of life and social costs may be identified in normal conditions of
      use.

PMID- 17001868
TI  - [Adult neurogenesis: from basic research to clinical applications].
AB  - Neural stem cells have recently been found in the central nervous system of adult
      rodents and humans. In defined conditions, these multipotent cells can generate
      the three major cell types of the nervous system (neurons, oligodendrocytes and
      astrocytes). These findings raise questions on the functional role of neural stem
      cells in the adult brain, and point to the possibility of novel therapeutic
      approaches. We have been investigating the functional consequences of neural stem
      cells for the adult circuits of the olfactory system. We are currently
      investigating this unexpected juvenile characteristic for cognitive functions.
      For instance, we are exploring the potential of brain adaptation brought into
      play by adult neurogenesis. Our most recent studies show that neurogenesis
      contributes to long-term adjustment of the mature brain. Many questions remain to
      be answered, however. To what extent can we distinguish and compare neuronal
      production during embryogenesis and adulthood? How does a newborn cell migrate
      and find its target? How is cellular fate decided? By showing correlations
      between the regenerative capacities and cognitive functions of the adult brain,
      our results have interesting implications for the use of endogenous neuronal stem
      cells for brain repair in patients with neurodegenerative diseases or brain
      injury due to stroke or trauma.

PMID- 17001869
TI  - [Epidemiology of glomerular diseases in Tunisia from 1975 to 2005. Influence of
      changes in healthcare and society].
AB  - Between April 1975 and March 2005, 4,436 cases of histologically proven
      glomerulonephritis (GN) were diagnosed by the same team at the Kidney Unit of
      Charles Nicolle Hospital in Tunis. Respectively 1,510, 1,419 and 1,509 cases were
      diagnosed in 1975-1985, 1985-1995, and 1995-2005. We compared trends in the
      incidence rates of the different types of GN and those of Tunisian indicators of
      health, social and economic status. The following differences were found between
      1975-1985 and 1995-2005:--As a proportion of all cases of GN, the frequency of
      amyloidosis fell from 12,6 % to 6,5 % (p < 0,0001). The 444 cases of amyloidosis
      observed during the study period were of type AA in 87 % of cases, and were
      related to chronic infectious diseases in 239 cases (54 %; pulmonary tuberculosis
      in 114 cases). The frequency of tuberculosis-associated amyloidosis fell during
      the study period, in parallel with the reduction in the incidence of tuberculosis
      in the Tunisian population (48,7 cases/100,000 inhabitants in 1983 to 20,17 in
      2004). Lupus nephritis accounted for 7.7 % of all cases of GN diagnosed in 1975
      1985, compared to 13 % in 1995-2005 (p < 0,00001). Increased exposure to sunlight
      and use of cosmetics could be involved in this increase.--The incidence of both
      proliferative endocapillary and membranoproliferative GN (as a proportion of all
      cases of GN) fell between 1975-1985 and 1995-2005, from 15,9 % and 21,6 % to 6,9
      % and 7,7 %, respectively (p < 0,0001). This matched a drop in the incidence of
      acute rheumatic fever in the Tunisian population, from 7,26/100,000 inhabitants
      in 1984 to 0,83 in 2004, probably as a result of public health measures and
      widespread use of antibiotics. The incidence of membranous GN increased from 11,1
      to 17,7 % in adults (p < 0,001) whereas it fell from 10,1 to 4,6 % in children (p
      < 0,01), possibly as a result of a nationwide HBV vaccination program launched in
      1995. The incidence of IgA nephropathy increased from 0,9 to 12,9 % in adults (p
      < 0,0001) and from 0,3 % to 18,4 % in children, but remained relatively stable in
      elderly adults. This study, conducted in a single center, by the same team, and
      using the same renal biopsy practices, confirms that the control of infectious
      diseases in Tunisia has led to a substantial regression of proliferative
      endocapillary and membranoproliferative GN and renal amyloidosis. Environmental
      factors, such as the adoption of western lifestyles, could explain the increase
      in lupus and IgA nephropathies.

PMID- 17001870
TI  - [Oncolor: a comprehensive cancer network in the Lorraine Region of France].
AB  - Legislation governing patients' rights and health care quality (March 2002)
      provided for the creation of healthcare networks intended to improve the
      management of patients with complex and/or chronic diseases. As defined in the
      Cancer Plan, activated in March 2003, an oncological healthcare network covers a
      particular French region, with the aim of offering patients equal access to the
      best available care and accompaniment, based on caregiver coordination, shared
      multidisciplinary tools, and communication. ONCOLOR, the regional cancer network
      launched in the Lorraine region in 1993, complies with these objectives.
      Nevertheless, its future development depends on continued dynamism, durable
      financial support, and regular evaluation of the benefits for patients and
      caregivers. The key words are professionalism and consensus.

PMID- 17001871
TI  - [Effects of antimalarial drugs and cardiomyocytes. Pathogenic approach and new
      therapeutic recommendations].
AB  - The cardiotoxicity of halofantrine was a major concern during the past decade.
      Other old antimalarials (quinine, mefloquine, etc.) and more recent drugs may
      carry a similar risk. Studies of ventricular repolarization and myocardial cells
      can throw light on these adverse effects. Studies of QT dispersion measured on
      the surface electrocardiogram and of QT dynamicity and variability (QT/RR slope)
      during long-term Holter recording help to identify patients at risk of drug
      induced ventricular arrhythmia. Such electrocardiographic investigations have
      shown that quinine, mefloquine and artemisinin derivatives do not alter
      ventricular repolarization. In contrast, halofantrine significantly increases QT
      dispersion and the QT regression slope. At the cellular level, most major
      antimalarial drugs inhibit potassium channels, which are regulated by the LQT1
      and HERG genes responsible for the congenital long-QT syndrome. We propose new
      recommendations for the use of these drugs in the treatment and prevention of
      malaria.

PMID- 17001872
TI  - [Toxicological analysis at the beginning of the third millennium: promising new
      applications and future implications].
AB  - Enormous progress has been made in clinical toxicology over the last two decades,
      notably in the detection of pollutants. Chromatographic techniques have now
      replaced colorimetric reactions, which were non specific and poorly sensitive.
      Mass spectrometry has largely supplanted immunological methods, and is now
      coupled to gas phase (GC-MS or GC-MS/MS), liquid phase (LC-MS or LC-MS/MS) or
      induced coupled plasma spectrometry (ICP-MS). Few substances responsible for
      clinical syndromes now escape detection, be they medicinal drugs, plant products,
      pesticides, drugs of abuse, drugs used for criminal purposes, metals, metalloids,
      or poisons. Forensic medicine has benefited from these advances, notably in the
      fields of post-mortem toxicology, driving under the influence of drugs of abuse,
      and drug-facilitated crime. Rapid advances are being made in occupational and
      environmental monitoring of new substances with poorly documented toxicity. The
      French National Health and Environment Program, launched on 9 August 2004,
      specifically takes this problem into account. The author presents recent personal
      laboratory results illustrating the potential of these new techniques.

PMID- 17001873
TI  - [Cell death and neurogenesis after hypoxia: a brain repair mechanism in the
      developing rat?].
AB  - Perinatal brain damage following hypoxia-ischemia has long been considered
      irreversible, but recent rodent studies show that various insults can induce de
      novo neurogenesis in the adult brain. Here we examined whether acute hypoxia
      could trigger neurogenesis in the developing rat brain. In vitro, we examined the
      impact of transient hypoxia on cultured embryonic rat neurons. In vivo, we
      monitored the time course of brain damage in the CA1 layer of the hippocampus of
      one-day-old rats after exposure to hypoxia. The extent of cell loss and
      regeneration was evaluated after staining with DAPI. Newly generated cells were
      characterized in the subventricular zone by immunohistochemistry, 20 days post
      exposure. The viability of cultured neurons was reduced by 36 % when measured 96
      h after 6 h of hypoxia, and a significant number of cell nuclei showed apoptotic
      features. In contrast, cell numbers increased by 14 % 96 h after 3 h of hypoxia.
      The Bax/Bcl2 ratio tended to increase after 6 h of hypoxia and to decrease after
      3 h of hypoxia. In the CA1 subfield of the hippocampus, hypoxia reduced the total
      number of cells by 27 % on day 6-7 post-reoxygenation, and histopathological
      hallmarks of apoptosis were observed This cell deficit was followed by gradual
      recovery, starting on day 20, suggesting a repair mechanism. BrdU incorporation
      in the subventricular zone showed an accumulation of proliferating cells
      expressing the neuronal marker NeuroD. These data show that post-hypoxic
      neurogenesis can occur during development.

PMID- 17001874
TI  - [What can we learn from genes responsible for familial forms of Parkinson's
      disease?].
AB  - During the past decade, the identification of several genes responsible for
      monogenic forms of Parkinson's disease has greatly increased our knowledge of the
      pathophysiological mechanisms of this disease. The alpha-synuclein gene, involved
      in very rare forms with autosomal dominant transmission, encodes a protein which
      is a major component of Lewy bodies, the histopathological hallmark of the
      disease. The Parkin gene, responsible for a significant number of cases with
      early onset, encodes an E3 ubiquitin-ligase, supporting the involvement of the
      ubiquitin-proteasome pathway in Parkinson's disease. Finally, mutations in the
      LRRK2 gene, which codes for a kinase with unknown substrates, accounts for a
      substantial fraction of autosomal dominant forms, particularly in North Africa.
      The study of these genes shows that the formation of Lewy bodies is not mandatory
      for the degeneration of dopaminergic neurons in Parkinson's disease. It remains
      to be determined whether the products of the genes are implicated in the same
      metabolic path way.

PMID- 17001875
TI  - [Imaginary chronicle of Louis XIV's ailments and contemporary illnesses].
AB  - Based on contemporary medical journals, the author examines the numerous ailments
      that afflicted Louis XIV and underlines the impoverishment of the medical art at
      a time when physicians' power was sovereign and when treatments were as bizarre
      as they were painful. This historical journey also serves as a pretext to examine
      current developments in the field of microsurgery, which can cure health
      disorders that were considered inaccessible to anatomical and functional
      amelioration.

PMID- 17001876
TI  - Pathogenesis and pathology of brain abscess.
AB  - Brain abscess continues to be a serious medical problem with increasing incidence
      despite advances in diagnostic and surgical methods, and advent of new
      antibiotics. This is due to increase in immune suppressed individuals,
      opportunistic pathogens and resistance to antibiotics. The morbidity, mortality
      and long term sequelae of brain abscess like cognitive impairment and poor
      neurological outcome are due to persistent release of proinflammatory mediators
      by activated microglia, astrocytes and infiltrating inflammatory cells, along
      with disruption of blood brain barrier. Anti-inflammatory drugs along with
      specific antimicrobial agents help in minimizing damage to the adjacent brain
      parenchyma. Identification of microorganisms in the aspirated material or the
      excised specimen help decide the optimal antimicrobial therapy. Prompt
      examination of smear and meticulous culture techniques to identify aerobes,
      anerobes, mycobacteria, actinomycetes, parasites and fungi are of utmost
      importance in choosing antibiotics. Histology complements culture and plays a key
      role especially in specific infections. Use of appropriate histochemical stains
      along with tissue reaction helps in diagnosis. The route of spread, the type and
      virulence of the organism, thickness of the capsule, location and number of
      abscesses in the brain, and immune status of the host are important determinants
      of outcome. Identification of microorganisms and insights into pathogenesis allow
      appropriate therapeutic interventions to improve outcome.

PMID- 17001877
TI  - Aortic dissection and bicuspid aortic valve: an autopsy study.
AB  - Medico-legal post-mortems referred to the Department of Pathology, for the
      histopathological examination, revealed six cases of acute aortic dissection--two
      in isolation, three in combination with congenital bicuspid aortic valve; and one
      isolated case of congenital bicuspid aortic valve. One case of isolated aortic
      dissection was associated with Marfan's syndrome; and one case of aortic
      dissection with bicuspid aortic valve was associated with polycystic kidneys.
      History of hypertension could be elicited in two cases. Cystic medial
      degeneration of aorta was seen in three cases; one of which was associated with
      Marfan's syndrome. All five cases of aortic dissection belonged to type II of
      DeBakey classification.

PMID- 17001878
TI  - Mammography-guided stereotactic fine needle aspiration cytology of breast
      lesions.
AB  - The purpose of the present study was to evaluate the efficacy of mammographic
      guided stereotactic fine needle aspiration cytology in 136 patients with breast
      lesions including mammographic features, cytomorphological findings and nuclear
      grading in malignant cases. Majority of the cases were predictable correctly by
      combination of the three modalities of diagnosis viz, clinical examination,
      mammography and cytology.

PMID- 17001879
TI  - Value of scoring system in classification of proliferative breast disease on fine
      needle aspiration cytology.
AB  - Fine-needle aspiration (FNA) cytology is successful in identification of benign
      and malignant breast lesions, but its role in proliferative breast lesions which
      increase cancer risk is poorly defined. We have analyzed the cytomorphologic
      features of proliferative breast lesions in conjunction with cytologic scoring
      system proposed by Masood et al and with histopathology. Sixty two patients (14
      cases of fibroadenoma, 15 cases of fibroadenoma with atypia, 11 cases of
      proliferative breast disease (PBD), 8 cases of PBD with atypia and 14 cases of
      carcinoma) diagnosed on routine FNA were subjected to scoring following Masood's
      criteria. All cases with the cytologic diagnosis of fibroadenoma were confirmed
      on histology. Of 11 cases of PBD on FNA, 10 were PBD without atypia on histology.
      One case, which showed atypical hyperplasia on histology, was missed by both the
      scoring system and cytomorphology and one case was over-diagnosed as PBD with
      atypia by the scoring system. FNA cytology correctly identified all the carcinoma
      cases, while the scoring system under-diagnosed 2 cases as PBD with atypia.
      Hence, in cases not suspected to be atypical or confirmed to be cancer on routine
      cytology, scoring added no information over and above cytomorphology and was not
      useful. All fourteen cases of fibroadenoma with atypia suspected on routine
      cytology were fibroadenoma on histology. Scoring system correctly placed 11/14 of
      these cases as PBD without atypia. Similarly 3/8 cases thought to be PBD with
      atypia were correctly placed as PBD without atypia by scoring. Only 2/8 cases
      thought to be PBD with atypia on cytology were confirmed to have atypical
      hyperplasia on histology. Scoring improved the diagnostic yield to 2/5. Hence, in
      cases of fibroadenoma or PBD, suspected on FNAC to have cytological atypia,
      Masood scoring gives additional information by eliminating benign cases and
      improving diagnostic yield. Application of scoring in a step-wise manner, on
      atypical aspirates, can help in selection of cases suitable for biopsy.

PMID- 17001880
TI  - Utilization of antihepatocyte clone OCH1E5 (Hep Par 1) in histological evaluation
      of liver tumors.
AB  - Diagnosis of hepatocellular carcinoma (HCC) is not always easy on simple
      hematoxylin and eosin (H&E) stain. The diagnostic problems arise when tumor shows
      pseudoglandular, pleomorphic or clear cell differentiation. Various tumors
      markers have been described with varying sensitivity and specificity. Monoclonal
      antibody Hep Par 1 (OCH1E5) which is specific for hepatocytes offers great help
      in separation of these tumors. The aim of the present study was to determine
      utility of Hep Par 1 (OCH1E5) in differentiating HCC from metastatic tumors and
      cholangiocarcinoma. Total of 62 cases of liver tumors obtained from biopsies,
      resected or autopsy specimens were included in the study. Slides having
      representative sections were subjected to immunohistochemistry with monoclonal
      antibody Hep Par 1 (Dako Corp) using avidin biotin technique with primary
      antibody dilution of 1:40. Adjacent nontumorous hepatocytes were taken as
      positive control. Slides were examined by experienced pathologist without any
      information of clinical or H&E diagnosis. Cases were considered positive for Hep
      Par 1 if tumor cells showed cytoplasmic brown colored granules. The intensity and
      distribution (diffuse/ focal) of immunoreactivity was noted. Subsequently
      immunohistochemistry results were correlated with histology and clinical
      diagnosis. Hep Par 1 antibody was positive in 26 (42 %) and negative in 36 (58 %)
      liver tumors. On correlating with H&E sections, out of 26 positive cases, 25
      (89.2%) were HCC and one was the case of metastasis of mucin secreting
      adenocarcinoma. From 36 tumors with negative staining 3 were cases of HCC, 27
      metastatic adenocarcinomas and 6 cholangiocarcinomas. Only one case of liver
      metastasis of mucin secreting adenocarcinoma showed positivity. None of the cases
      of cholangiocarcinoma showed positivity for Hep Par 1. The three HCCs which did
      not take up staining for Hep Par 1 were 2 cases of moderately differentiated HCC
      having pseudoglandular pattern and a case of well differentiated HCC with
      trabecular arrangement. In 11(44%) cases staining was diffuse while in 14 (56%)
      it was focal but intense. Hep Par 1 is a useful marker in differentiating HCC
      from metastaic tumors and cholangiocarcinoma with sensitivity and specificity of
      89 % and 97 % respectively and positive predictive value of 96 %. However one
      should be aware of limitations of immunohistochemistry.

PMID- 17001881
TI  - Detection of HPV16 and 18 by in situ hybridization in precancerous and cancerous
      lesions of cervix.
AB  - Fifty cervical biopsies from women with preinvasive and invasive malignancies of
      uterine cervix and ten normal cervical biopsies were examined for the presence of
      human papilloma virus (HPV) 16 and 18 DNA sequences by in situ hybridization
      (ISH) method with biotinylated DNA probes. The overall positivity of HPV DNA was
      48% (24/50). The positivity of HPV 16 DNA for low grade squamous intraepithelial
      lesion (LSIL), high grade squamous intraepithelial lesions (HSIL) and squamous
      cell carcinoma (SCC) were 33.33%, 45.45%, 42.30% respectively. The positivity for
      HPV 18 DNA for LSIL, HSIL and SCC were 0%, 18.18%, 30.76% respectively. Two cases
      of cervical adenocarcinomas showed positivity for HPV 18 DNA only.

PMID- 17001882
TI  - Application of domestic microwave for urgent histopathology reporting: an
      evaluation.
AB  - Rapid diagnosis of histopathological material is becoming increasingly desirable.
      In neuropathology, crush smear preparation and frozen section diagnosis of
      tissues removed during operative procedures, have remained as essential tools for
      rapid diagnosis. Microwave technology has been introduced into the field of
      tissue processing and staining in past decade. Now-a-days even automated
      microwave assisted rapid tissue processors are available. In our study we have
      analysed the use of a domestic microwave (cost approximately Rs.5000) for urgent
      histoprocessing (30 minutes). This could be useful in small laboratories or the
      ones which are in the phase of establishing the department as the procedure is
      much more economical than obtaining a frozen section (which requires a cryostat
      worth 3-6 lakhs) and the interpretation of the section obtained does not require
      any extra experience as these resemble the routinely processed tissue sections.
      The advantages and limitations of the procedure have been discussed.

PMID- 17001883
TI  - Histopathological changes in gastric mucosa colonized by H. pylori.
AB  - Helicobacter pylori (H. pylori), infection has been linked to acute and chronic
      gastritis, non-ulcer-dyspepsia, peptic ulcer, gastric adenocarcinoma and gastric
      non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT). The
      epithelial changes in H. pylori colonized gastric mucosa are easy to recognize in
      routine Haematoxylin & Eosin stained sections and are so distinctive that they
      can serve as a helpful histological indicator for the presence of H. pylori in
      gastric biopsies. The histopathology of seventy-five gastric biopsies showing
      colonization by H. pylori was studied. Histologically, the H. pylori colonized
      gastric epithelium showed characteristic changes that were topographically
      related to the bacteria. These changes included irregular surface, epithelial
      pits, individual cell dropout and microerosion, which were specific for H. pylori
      colonization. These were absent in areas not colonized by H. pylori and in 20
      consecutive H. pylori negative gastric biopsies seen during the same study
      period. As specific treatment for H. pylori infection is available,
      identification of H. pylori colonization in gastric biopsies should be attempted
      in all cases of gastritis, peptic ulcers and non-ulcer-dyspepsia.

PMID- 17001884
TI  - Comparative analysis of HBV and HCV infection in hepatocellular carcinoma and
      chronic liver disease--an autopsy based study.
AB  - Hepatocellular carcinoma (HCC) is one of the common malignancies worldwide
      including Asian countries. Chronic viral hepatitis is implicated as an important
      etiological factor in carcinogenesis of liver. AIM: To study incidence of
      hepatitis B (HBV) and C (HCV) viruses in HCC and to compare the incidences with
      that of chronic liver disease. MATERIALS AND METHOD: 40 cases each of HCC (group
      I) and chronic liver disease including cirrhotic liver (group II) who died of the
      liver disease. All cases were stained with HBsAg and HBcAb for HBV and RT-PCR for
      HCV RNA. Different groups were compared using student's t-paired and chi-square
      tests. RESULTS: Group I--HCC was seen in 37 cirrhotics and 3 non-cirrhotic cases.
      HBsAg was positive in 32 cases (80%), HBcAb in 22 cases (55%) and HCV in 23 cases
      (57.5%) (p<0.05). Dysplastic nodule (DN) was seen in 25 cases, HBsAg and HBcAg
      positivity were seen in 18 and 15 cases respectively. Group II--32 cases were
      cirrhotic and 8 were non-cirrhotics. HBsAg was positive in 28 (70%), HBcAb in 12
      (30%) and HCV in 18 (45%) cases. DN was seen 24 cases, HBsAg and HBcAg postiviy
      were seen in 16 and 7 cases respectively. HBV and HCV co-infection was seen in 20
      and 15 cases, and HCV with HBcAb positivity was seen in 13 and 9 cases in groups
      I and II respectively. Number of cells in each case showing positivity for HBcAb
      was also significantly higher in group I (p<0.01). Age and sex distribution did
      not show any distinctive differences between the two groups. CONCLUSION: the
      study highlights a high incidence ofHBVand HCV infection in cases of chronic
      liver disease and HCC. HBcAb positive state appears to be an independent risk
      factor for HCC.

PMID- 17001885
TI  - Pattern of fibronectin in hepatocellular carcinoma and its significance.
AB  - Fibronectin is a multifunctional large molecular weight glycoprotein that can
      bind extra-cellular and cellular components. The aim of the present study was to
      evaluate expression of fibronectin and its significance in cases of
      hepatocellular carcinoma (HCC). A few previous studies have shown abnormal over-
      expression of fibronectin in cases of HCC. Expression of the fibronectin protein
      was studied in eleven cases of HCC by immunohistochemical method. Fibronectin was
      seen to localize predominantly in perisinusoidal region and strong positivity was
      noted in other fibrotic areas. Positivity around nests of cells and tumor nodules
      was noted in 8/11 cases of HCC and faint cytoplasmic positivity in tumor cells
      was seen in 5/11 cases. Staining pattern of fibronectin in HCC was definitely
      abnormal but decreased in the present study. The controversial results as seen in
      few previous studies also have been partially explained in the present article
      and further studies using larger sample size is suggested to clarify the issue.

PMID- 17001886
TI  - Microfilariae in fine needle aspirates: a report of 22 cases.
AB  - The objective of the study is to document the value of fine needle aspiration
      cytology (FNAC) in the diagnosis of filariasis at all possible sites in both
      exfoliative cytologic material and fine needle aspirates. Both unguided and
      guided FNACs of all foci were studied over a period of two years between 1999 to
      2000. Total 22 cases of filariasis were detected which included subcutaneous
      swellings(7), breast(3), thyroid(3), lymphnodes(3), effusions(3), cervical
      scrape(1), eyeball(1), sputum(1) and bronchial washing(1). In none of these cases
      was filariasis considered a diagnostic possibility. Cytologic smears showed
      eosinophils in 9 cases, oval ova and embryonated eggs in 2 cases. Microfilariae
      were associated with other diseases in 13 cases, including 6 cases of malignancy.
      Significant adherence of inflammatory cells and macrophages to microfilariae was
      present in 6 of the 22 cases. In endemic areas,filariasis should be considered
      one of the differential diagnosis of a swelling. Thus demonstration and
      identification of the parasite in cytologic smears played a significant role in
      the prompt recognition of the disease and institution of specific treatment, thus
      obviating the more severe manifestations of lymphatic frilariasis.

PMID- 17001887
TI  - Role of gel based technique for Coomb's test.
AB  - The direct (DAT) and indirect antiglobulin tests (IAT) are one of the most
      important diagnostic tools used in the investigation of immune mediated
      disorders. Recently, transfusion laboratories have seen the introduction of
      column technology in the form of the gel technology (GT). Aim of this study is to
      compare the conventional tube tests (CTT) and the GT for Coomb's test and to
      evaluate their sensitivity and specificity. 1656 samples were included in this
      study, in which 1054 samples were subjected to IAT and 602 samples were subjected
      to DAT Of the 602 samples tested for DAT, 587 (97.5%) showed concordant DAT
      results. DAT by the GT could detect 8.6% positivity as compared to 6.1% by CTT.
      The sensitivity and specificity of the GT was 100% and 97.3% respectively and its
      negative predictive value was 100%. Among the 1054 samples for IAT, 1041 (98. 8%)
      showed concordant results. The IAT by the GT showed 6.6% positivity as compared
      to 5.4% positivity by CTT The sensitivity, specificity and the positive and
      negative predictive value were 100%, 97.7%, 81.4% and 100% respectively. In
      conclusion, the GT is a better alternative to the CTT for both DAT and IAT. The
      GT is highly recommended to be implemented as a routine method of testing in all
      zonal / regional blood transfusion centers.

PMID- 17001888
TI  - Spectrum of anemia in pregnant Indian women and importance of antenatal
      screening.
AB  - Anemia is a common health problem but control of anemia in pregnant women is less
      well studied. The purpose was to study prevalence of anemia in young pregnant
      women, correlate with indices and study significance of identification of
      hemoglobinopathies. Of the 120 pregnant women, Hb was less than 8 g% in 58
      (44.2%). Seventy-eight (65%) had iron deficiency, 22 (18.3%) had dimorphic
      anemia, and 14 (11.6%) had hemolytic anemia. Megaloblastic anemia was present in
      6 (5%). Of hemolytic anemia, 50% were thalassemia trait. MCV< 76 fl was observed
      in 88 (73.3 %) cases. MCV<76 fl and MCH < 27 pg had 100 % sensitivity and 28.7 %
      specificity for screening of beta-thalassemia trait. NESTROFT had comparable
      sensitivity but lower specificity (14.9%). Sixty-three percent (60/78) of IDA had
      increased RDW whereas 78 % (11/14) of hemolytic anemia had RDW value in normal
      range (p value< 0.05). MCV/RBC of <14 was more specific parameter (96.8%) for
      beta-thalassemia trait. Four high-risk couples were identified. Thus, moderate to
      severe anemia was observed in most pregnant women. Hemoglobinopathies should be
      screened in antenatal clinics to identify the couples that would need a prenatal
      test. A lower MCV/RBC with RDWin the normal range may be useful in screening for
      thalassemia trait in pregnant women.

PMID- 17001889
TI  - Utility of galectin 3 expression in thyroid aspirates as a diagnostic marker in
      differentiating benign from malignant thyroid neoplasms.
AB  - Galectin-3 is a 31kD beta-galactoside binding lectin, which is known to be
      expressed in various neoplasms including thyroid tumors. This study was conducted
      to study the role of galectin-3 in differentiating benign from malignant thyroid
      nodules onfine needle aspirates (FNAC). Galectin-3 immuocytochemistry was
      performed in 70 cases with adequate smears. The cytology diagnosis of these cases
      was: papillary carcinoma (25), follicular neoplasm (16), adenomatous goiter (20),
      hyperplastic nodule (5), medullary carcinoma (5) and anaplastic carcinoma (1).
      Galectin-3 positivity was seen in 80% of papillary carcinomas, 37.5% offollicular
      neoplasms and in 60% of benign nodules. The single case of anaplastic carcinoma
      was positive but all the cases of medullary carcinoma were negativefor galectin
      3. Three of thefollicular neoplasms that were diagnosed on histology as carcinoma
      were positive on cytology and one case offollicular adenoma was also positive.
      Our study shows that galectin-3 is strongly expressed in smears of papillary
      carcinoma. However, since it is also expressed in a variety of benign lesions,
      its role as a pre-surgical markerfor differentiating benignfrom malignant thyroid
      nodules is limited.

PMID- 17001890
TI  - Blood collection procedures in hematology: knowledge and practice among
      laboratory personnel.
AB  - Blood collection is an important preanalytical component of haematological
      testing. This questionnaire based study was conducted on laboratory personnel to
      elicit their knowledge and practice regarding blood collection procedures for
      haematological testing. Questionnaire comprised of 37 multiple choice questions,
      of which 10 questions each were related to essential and desirable knowledge, 10
      to practice and 7 to educational and job profile. Ninety four laboratory
      personnel participated in the study. Analysis was done on SPSS software.
      Percentages of unsatisfactory scores were 42.6%, 4.3%, 17% and 6% in the
      essential knowledge, desirable knowledge, practice and total scoring
      respectively. 91.5%, however, had a satisfactory total score. Importance needs to
      be given to blood collection procedures both, individually and collectively. The
      study highlights the deficient areas which need to addressed by all
      laboratorians. Such studies should also be conducted among nursing and resident
      staff- the other groups concerned with blood collection.

PMID- 17001891
TI  - Tubercular dacryoadenitis--a case report and review of literature.
AB  - A case of a 56 year old lady presenting clinically with a slow growing painless
      mass of the left lacrimal gland, the histopathplogical examination of which was
      consistent with a diagnosis of tubercular dacryoadenitis, is described.
      Tubercular dacryoadenitis is uncommon, with the diagnosis usually made on
      histological examination of the lacrimal gland. Other cases of tubercular
      dacryoadenitis reported in literature are also reviewed.

PMID- 17001892
TI  - Myxoid liposarcoma of the breast--report of a rare case.
AB  - Breast sarcomas are very rare. A 40 year old lady presented with a well-defined
      hard lump, 6 cm in size, in the left breast. Patient underwent simple mastectomy
      with axillary clearance following a diagnosis of phylloides tumour on fine needle
      aspiration cytology. Grossly, it was a circumscribed myxoid tumour.
      Histopathologically, it fulfilled all the criteria for a diagnosis of myxoid
      liposarcoma. The absence of epithelial component excluded phylloides tumour.

PMID- 17001893
TI  - Focal eosinophilic myositis--a rare cause of pseudotumor.
AB  - Idiopathic focal eosinophilic myositis is a rare benign pseudotumor of skeletal
      muscle of unknown cause, characterized by focal eosinophilic infiltration of
      striated muscle. It can mimic a soft tissue sarcoma clinically and on gross
      examination of the specimen. Microscopic examination establishes the diagnosis.
      It is important to recognize this pseudosarcomatous lesion so as to spare the
      patient from anxiety.

PMID- 17001894
TI  - Endovascular papillary angioendothelioma in an elderly female.
AB  - Endovascular papillary angioendothelioma (EPA) is a rare vascular tumor of low
      grade malignancy, encountered primarily in children. However some cases have also
      been reported in adults. A sixty year old female with EPA is described here. She
      presented with a swelling in the neck. Total surgical excision was performed.
      Histomorphology revealed anastomosing lymphatic channels showing intraluminal
      papillary fronds with hyaline vascular cores and hobnailing of endothelial cells.
      A diagnosis of EPA was made based on this picture. This tumor is recurrent and
      nodal metastasis has been reported in some cases.

PMID- 17001895
TI  - Calcifying fibrous pseudotumor of the soft palate--a case report.
AB  - Calcifying fibrous pseudotumor has recently been described in the soft tissues.
      It is a rare benign lesion characterized by the presence of abundant hyalinized
      collagen with psammomatous or dystrophic calcification, and lymphoplasmacytic
      infiltrate. We report one such rare case in an 18 year old female with a nodular
      mass in the soft palate treated by complete resection. The mass had all the
      pathologic features of a calcifying fibrous pseudo-tumor.

PMID- 17001896
TI  - Esophageal cyst--a case report.
AB  - Mediastinal cysts are rare and classified into thymic cysts, bronchogenic cysts,
      enteric cysts, pericardial cysts, lymphatic cysts and other rare types. We
      describe a case of foregut cyst of esophageal type in a 22 day old male infant.
      The CT scan showed a cystic lesion. Excised cyst was bilocular and was filled
      with clear fluid. Microscopically, the cyst was lined by columnar epithelium with
      well formed lamina propria and double layered muscularis. In view of presence of
      double layer of muscularis and absence of gastric glands, intestinal epithelium
      or cartilage, it was classified as esophageal cyst. We report this case of
      esophageal cyst because of its rarity.

PMID- 17001897
TI  - Malignant peripheral nerve sheath tumor in oral cavity--a rare site.
AB  - MPNST occurring in oral cavity, which is a rare site for the tumour, in a 35 year
      old female patient with history of swelling underneath the tongue present since
      one year diagnosed clinically as ranula is presented here. Histopathological
      examination of the excised mass showed features of spindle cell sarcoma following
      which a provisional diagnosis of MPNST was offered. The differential diagnosis
      considered were leiomyosarcoma, rhabdomyosarcoma and spindle cell variant of
      squamous cell carcinoma (being the commoner tumour in oral cavity).
      Immunohistochemistry confirmed neural origin of the tumour. The case is reported
      in view of the rarity of the lesion in oral cavity.

PMID- 17001898
TI  - Epithelial myoepitheial carcinoma of minor salivary gland--low grade malignant
      tumor presenting with nodal metastasis.
AB  - Epithelial myoepithelial carcinoma (EMC) is a rare low grade malignant salivary
      gland neoplasm that most commonly occurs in the parotid gland but can also arise
      in minor salivary glands. We report a case of primary epithelial myoepithelial
      carcinoma of minor salivary gland in a 25 year old women who presented with
      swelling left cheek of one year duration and bilateral submandibular
      lymphadenopathy. A mass causing erosion of mandible, thyroid cartilage and
      masseter muscle was identified on CT scan. This was excised and histological
      examination revealed a mixture of ductal structures consisting of inner dark
      cells and outer clear cells seen in solid sheets. Immunohistochemical analysis
      showed the clear cells to be weakly positive for S100 and smooth muscle actin
      (SMA) and ductal cells to be positive for cytokeratin (CK) and epithelial
      membrane antigen (EMA). The characteristic morphological and immunohistochemical
      features aided in the diagnosis of epithelial myoepithelial carcinoma.

PMID- 17001899
TI  - Paratesticular liposarcoma--a case report.
AB  - A case of paratesticular liposarcoma in a 60 year male is presented for its
      rarity. The tumour was a dedifferentiated liposarcoma (DDL) seen in the original
      excision.

PMID- 17001900
TI  - Parathyroid lipoadenoma: case report and review of the literature.
AB  - Parathyroid lipoadenoma is a rare variant of parathyroid adenoma showing
      intermingling of chief/ oxyphil cells with abundant mature adipose cells, the
      latter comprising 20-90% of the tumour. Approximately thirty-five cases have been
      reported previously. We report a case of 41-year old woman who presented with
      clinical manifestations of primary hyperparathyroidism. She had elevated serum
      calcium and parathyroid hormone levels. Radiological investigations suggested
      presence of adenoma. Intra-operatively, parathyroid adenoma was found in the neck
      in an ectopic location behind the carotid sheath and extending into the superior
      mediastinum. Clinicopathological findings of this rare tumour are discussed.

PMID- 17001901
TI  - Solid and papillary epithelial neoplasm of the pancreas--a case report.
AB  - Solid and papillary epithelial neoplasm (SPENP) of the pancreas is a rare
      pancreatic tumour of low malignant potential, that is seen mostly in young
      females. The aetiology and pathogenesis is unclear but it is considered to be
      arising from primordial pancreatic cells. We report two cases of SPENP who had
      palpable abdominal lumps and were diagnosed on histopathology. In the first case,
      the tumour was unresectable and patient died within one year. In the second case,
      at laprotomy the patient had perineurial as well as capsular infiltration but
      after wide resection of the growth, patient has been doing well for the past 6
      months. Since SPENP is a low grade malignant neoplasm, it should be treated
      aggressively with complete resection and metastatectomy. Prognosis after adequate
      surgery is good. A clinicopathological study and brief review of literature is
      presented.

PMID- 17001902
TI  - Primary mucinous carcinoma of urachus--a case report.
AB  - The authors describe a case of primary mucinous carcinoma of urachus in 65 years
      old male. Patient presented with hematuria with suprapubic mass. The patient
      underwent total cystectomy with en bloc excision of the tumor mass and umbilicus.
      Histological examination showed features of mucinous carcinoma of urachus. A
      clinicopathological study and brief review of literature is presented.

PMID- 17001903
TI  - Cytomorphological features of nodular hidradenoma highlighting eccrine
      differentiation: a case report.
AB  - We report a case of nodular hidradenoma in a 90 year old male, presenting with an
      eyelid swelling. The cytomorphological features are described with special
      emphasis on cytoplasmic granularity and tubule formation as an important feature
      in diagnosing and differentiating eccrine tumors from other adnexal neoplasms on
      FNAC.

PMID- 17001904
TI  - Epididymo-testicular malacoplakia--a case report.
AB  - Malacoplakia is one of the rare, chronic inflammatory disorders affecting the
      epididymis and testis. Diagnosis of the same is important as the treatment
      differs from the other granulomatous lesions in this area. We present a case of
      malacoplakia involving both the epididymis and testis with a brief review of
      literature.

PMID- 17001905
TI  - Variation in clinical and genitourinary lesions associated with pulmonary
      hypoplasia in Potter's syndrome--two autopsy reports.
AB  - Potter's syndrome is a rare entity with an incidence of 1 in 2000 to 1 in 5000
      live births. All babies born with this condition are either stillborn or die very
      early within neonatal period. We present two autopsy cases which presented with
      abnormal facies, oligohydramnios, pulmonary hypoplasia and genitourinary
      abnormality. One case presented with infantile polycystic kidney whereas in the
      other case both the kidneys were normal but had adenomatoid tumour of left
      testis. Both the children died few hours after birth. In both the cases pulmonary
      hypoplasia was the cause of death rather than genitourinary abnormality.

PMID- 17001906
TI  - Primary squamous cell carcinoma of the renal pelvis masquerading as pyonephrosis:
      a case report.
AB  - Squamous cell carcinoma of the renal pelvis is a rare tumor, which is usually
      associated with nephrolithiasis. It is rarely associated with pyonephrosis. We
      report the case of a 69-year-old man who presented with features of pyonephrosis
      and underwent nephrectomy. The postoperative histological evaluation revealed an
      unsuspected squamous cell carcinoma of renal pelvis with a concomitant
      pyonephrosis. The rarity of this tumor in the absence of renal calculi and its
      association with pyonephrosis is highlighted.

PMID- 17001907
TI  - Coexistence of a mature teratoma and mucinous cystadenocarcinoma in the same
      ovary--a case report.
AB  - A case of right sided abdominal lump with pain in a 45 years female was
      presented. Radiological investigation revealed a multiloculated cystic mass with
      a few mural nodules arising from right ovary. The tumor was removed by
      exploratory laparotomy and histopathological examination showed coexistence of
      dermoid cyst with mucinous cystadenocarcinoma in the same ovary. Left ovary and
      uterus was healthy and there was no tumor extension or omental deposits.
      Postoperative period was uneventful.

PMID- 17001908
TI  - Chondroid lipoma--a case report.
AB  - Chondroid lipoma is a rare fatty tumor of soft tissues, especially in limbs and
      limb girdles. Though it is clinically benign, the main importance lies in its
      histological similarity with myxoid liposarcoma and chondrosarcoma, which have
      poorer prognosis. In our study, classical histological pattern of chondroid
      lipoma was confirmed on H&E and PAS stains with low mitotic count.

PMID- 17001909
TI  - Unsuspected metastatic renal cell carcinoma with initial presentation as solitary
      soft tissue lesion: a case report.
AB  - A 42 year old male presented with painless soft tissue mass 8x7x6.5 cm in right
      scapular region for 2 months. Fine needle aspiration cytology (FNAC) showed a
      malignant clear cell tumour. Ultrasonography (USG) abdomen revealed a
      heterogeneous mass m 8.6x7x8.4 at the lower pole of left kidney. USG guided FNAC
      from left kidney mass showed cytomorphology consistent with RCC.

PMID- 17001910
TI  - Unilateral retinal dysplasia--a case report.
AB  - Retinal dysplasia is an uncommon condition and may be either unilateral or
      bilateral. It represents disturbed differentiation of neural ectoderm. It can be
      sporadic or may be associated with genetic defects. A case of unilateral retinal
      dysplasia in a 2 year old male child is reported.

PMID- 17001911
TI  - Atypical stromal cells in inflammatory pseudopolyps--a case report.
AB  - Atypical stromal cells have been reported in inflammatory lesions of the
      gastrointestinal tract. We report a case of ulcerative colitis with pseudopolyps,
      histology of which showed bizarre stromal cells. These atypical stromal cells
      simulate malignant cells and pose a diagnostic problem for surgical pathologists.
      It is therefore important to recognize these benign stromal cells as reactive
      thereby reducing unnecessary surgery.

PMID- 17001912
TI  - Antemortem diagnosis of gastrointestinal mucormycosis in neonates: report of two
      cases and review of literature.
AB  - Gastrointestinal mucormycosis has been reported more frequently in adults than in
      children. Due to high mortality diagnosis is usually made at autopsy. Only 3
      cases of neonates surviving this disease have been described. We report two cases
      of preterm neonates presenting clinically with symptoms of necrotizing
      enterocolitis (NEC), but lacking radiological characteristics of NEC where
      histopathology confirmed the diagnosis of gastrointestinal mucormycosis involving
      caecum and appendix.

PMID- 17001913
TI  - Tumoral calcinosis--clinicopathological study of five cases.
AB  - Five cases of tumoral calcinosis were studied during the period of January
      february 1999 in MIMER medical college, Talegaon, a rural place 35kms. from Pune.
      All the Five patients were females residing in nonendemic area for Dracunculosis.
      They were from 5th-6th decade. They were otherwise healthy and had normal serum
      calcium and phosphorus levels and no eosinophilia. All had large, hard
      subcutaneous lump around hip joint. The skin overlying the swelling was normal.
      Histologically all cases showed similar morphology, the lesions were composed of
      large and small deposits of calcium. The foreign-body giant cell reaction was
      seen in two cases. There were no eosinophils and lymphocytes. On multiple
      sectioning none of the cases revealed any evidence of dead or living parasite.
      Old and recent necrosis was absent. These cases are presented since the condition
      is comparatively rare and it appeared in crops in our Institute.

PMID- 17001914
TI  - Primary Hodgkin's disease of spleen--a case report.
AB  - Primary malignant lymphoma of spleen is rare with primary Hodgkin's disease (HD)
      of spleen being rarer. The diagnosis of primary splenic HD is usually made on the
      histopathological examination of the splenectomy specimen. We report an
      interesting case of primary HD of spleen in a child emphasizing its rarity and
      the role of fine needle aspirate cytology in early diagnosis and non-surgical
      management of this entity.

PMID- 17001915
TI  - Plasma cell leukemia with pleomorphic plasma cells--a case report.
AB  - A case of plasma cell leukemia showing mostly pleomorphic plasma cells in the
      form of convoluted and multilobated nuclei with some having bilobed nuclei and
      internuclear bridges is being reported for its rarity of occurrence. Patient
      presented with congestive cardiac failure and features of nephropathy. There were
      no lytic lesions in the bone. Serum electrophoresis did not show any M-band while
      urine electrophoresis demonstrated Bence Jones protein confirming a light chain
      only type of myeloma. Patient is in remission 5 months after diagnosis. The
      significance of recognising such pleomorphic plasma cells is discussed.

PMID- 17001916
TI  - Painless angioleiomyoma: a case report with review of literature.
AB  - A 55 year old male, who presented with a painless swelling of six months duration
      on his thigh, was clinically diagnosed to have a benign soft tissue neoplasm.
      Histological examination of the excision biopsy specimen revealed a benign tumour
      of the vascular smooth muscle, which was diagnosed as angioleiomyoma.
      Angioleiomyomas are painful lesions that can occur anywhere in the body. We
      present this case for its atypical clinical presentation and discuss its
      histologic features with a review of literature.

PMID- 17001917
TI  - CD10 in diffuse uterine leiomyomatosis: a case report along with a few comments
      on histogenesis.
AB  - Diffuse uterine leiomyomatosis (DUL) is a rare entity with an unknown
      etiopathogenesis. A 24 years old female presented with abdominal discomfort and
      menorrhagia. Clinical and ultrasonographic examination revealed an enlarged
      uterus. The hysterectomy specimen showed a symmetrically enlarged uterus with a
      bosselated external surface. The cut surface showed multiple nodules of varying
      sizes diffusely involving the myometrium. Microscopically, the nodules were
      leiomyomas of varying degrees of cellularity. Some of the leiomyomas showed an
      increased vascularity either in the form of congeries of blood vessels with a
      lobular arrangement or occasionally as foci of 2-3 vessels. The vessels were
      surrounded by whorls of spindle cells. On immunohistochemistry the leiomyomas
      expressed vimentin, smooth muscle actin (SMA), desmin and CD10: the cells
      whorling around the blood vessels expressed vimentin, SMA and focally desmin and
      were negative for CD10 and HMB-45. The aim of this paper is to document that CD10
      is expressed in diffuse uterine leiomyomatosis and discuss the histogenesis of
      DUL.

PMID- 17001918
TI  - Multiple non-odontogenic cysts--a case report.
AB  - Nonodontogenic cysts have been identified at various locations in oral cavity.
      These occur primarily in relation to fusion of maxillary process either with its
      counterpart or different portions of nasal part of frontonasal process. Usually
      solitary, these primarily affect maxilla alone; can rarely be seen in ramus of
      mandible. We present a case of multiple non-odontogenic cysts involving both
      maxilla and mandible.

PMID- 17001919
TI  - Oxyphilic cell adenoma of parathyroid resulting in primary hyperparathyroidism
      and osteitis fibrosa cystica--a case report.
AB  - Adenomas of the parathyroid gland, the majority of which are of the solitary
      chief cell type, are the most frequent cause of primary hyperparathyroidism
      (pHPT). Parathyroid adenomas composed predominantly or exclusively of oxyphil
      cells are rare and most oxyphil cell adenomas of this organ remain clinically
      silent. We present here a case of hyperfunctioning oxyphil cell adenoma of the
      parathyroid gland resulting in pHPT, osteitis fibrosa cystica and simultaneous
      bilateral fractures upper shafts of femora.

PMID- 17001920
TI  - Chromobacterium violaceum: a case report of an unusual bacterium causing
      puerperal sepsis.
AB  - Human infections by Chromobacterium violaceum are rare. Till date 6 cases have
      been reported from southern and eastern parts of India. We report here a case of
      puerperal sepsis by C. violaceum, probably the first case from Eastern part of
      Orissa. The patient was successfully treated with amikacin and gatifloxacin.

PMID- 17001921
TI  - Disseminated histoplasmosis mimicking laryngeal carcinoma from central India--a
      case report.
AB  - A 58 year old male, chronic smoker, with diabetes mellitus (Type II), residing in
      Madhya Pradesh presented with dysphagia, hoarseness, odynophagia and significant
      weight loss. Microlaryngoscopy showed reddish ulcerated area involving
      valleculae, and pharyngo-epiglottic fold. Histopathological examination showed
      foamy macrophages containing Histoplasma capsulatum. Patient initially responded
      to Azoles, relapsed three months after stopping the treatment and presented with
      oral lesions. Biopsy showed H. capsulatum, histologically as well as on culture.
      The mycelial phase converted to yeast phase on B.H.I.A. at 37 degrees C
      confirming the isolate as H. capsulatum. The patient responded well to
      amphotericin B.

PMID- 17001922
TI  - Isolation of Vibrio mimicus from a case of acute diarrhoea--a case report.
AB  - Over a four months period (June to September, 2003) 111 stool samples from cases
      of acute diarrhoea were screened for Vibronaceae in department of microbiology,
      Smt. N. H. L. Municipal medical college, Ahmedabad. All the isolates were
      identified by standard laboratory technique. A total of 36 species belonging to
      Vibrionaceae were isolated. Phage typing of all these Vibronaceae were done at
      National Institute Of Cholera and Enteric Disease, Kolkata. Out of 36 isolates,
      35 were Vibrio cholereae and only one was Vibrio mimicus. We report this case
      because of rare strain.

PMID- 17001923
TI  - Vaginal microflora in postmenopausal women on hormone replacement therapy.
AB  - To study the spectrum of vaginal microflora in postmenopausal women on hormone
      replacement therapy (HRT) and to compare the efficacy of Papanicolaou (Pap)
      smears with other methods for their detection. Eighty postmenopausal women were
      recruited for the study. These included 40 women who had attained spontaneous and
      were on HRT (User 1); 20 hysterectomised women on only estrogen therapy (User 2)
      and 20 controls (Non users). Their clinical data was recorded and specimens were
      collected for vaginal cultures (for aerobic bacteria and fungi), vaginal pH, Gram
      stain and Pap stain on cervical-vaginal smears and toluidine blue on wet smears.
      Vaginal pH was significantly lower in Users as compared to Non users.
      Lactobacilli and Gardnerella were more frequently isolated from Users while
      Bacteroides and E. coli were more common in Non users. Cultures were
      significantly more sensitive than Gram stained direct vaginal smears in detection
      of aerobic bacteria; however, Candida could be detected on Gram stain alone in
      all the cases. Frequency of detection of organisms significantly improved by
      application of Gram stain to the cervico-vaginal smears. However, clinically
      relevant organisms like Candida, Gardnerella and Mobiluncus could be identified
      on Pap smears alone in >50% cases. Lactobacilli could be readily identified in
      Pap smears in 98% cases. Wet mounts could detect cocci more easily as compared to
      Pap smears. Altered vaginal microbial profile in post menopausal women receiving
      HRT may cause bacterial and fungal vaginitis. Although culture studies remain the
      gold standard to detect these microorganisms, Pap and Gram stains and wet smears
      provide useful supplements and may be used as alternative procedures especially
      in resource limited settings lacking adequate culture facilities.

PMID- 17001924
TI  - Incidence of dengue in a tertiary care centre--Kasturba Hospital, Manipal.
AB  - Dengue is the most important Arbovirus in the world in terms of occurrence and
      impact. It has been responsible for some devastating outbreaks and accounts for
      nearly 50-100 million cases of dengue fever and 2-5 lac cases of the dengue
      hemorrhagic fever worldwide. Dengue is caused by an arbovirus, which belongs to
      the Flaviviridae and is maintained in nature principally through biological
      transmission between susceptible vertebrate hosts by hematophagous arthropods.
      The incidence and global distribution of dengue has greatly increased in recent
      years and affects almost every country between the topics of Capricorn and
      Cancer. Although outbreaks of dengue fever has been occurring with regularity all
      over the country, and there have been 2 reported outbreaks in the neighboring
      district Mangalore in 1993 and 1996, there has been no reported outbreak in
      Manipal, which is what is responsible for the present study. In the study, out of
      the 100 clinically suspected cases of dengue, 44% tested positive for dengue IgM
      antibody, thus proving current dengue infection. Twenty six cases were from
      Shimoga district, which indicates increased dengue virus activity in this area
      and the possible endemicity in the region.

PMID- 17001925
TI  - Aerobic bacterial isolates from choledochal bile at a tertiary hospital.
AB  - We studied the aerobic bacterial isolates from bile and their susceptibilty
      pattern in patients with biliary tract disease. Samples of bile collected during
      endoscopic retrograde cholangio pancreatography (ERCP) and surgery, were
      inoculated on standard media. Bacterial identification and susceptibility were
      done by standard techniques. A total of 209 samples were cultured, out of which
      128 samples showed growth. Total number of isolates obtained was 221. Poly
      microbial infection was detected in 67 patients. Predominant aerobic bacterial
      isolates obtained were Escherichia coli 30% (67), Klebsiella species 23.98% (53),
      Enterococcus species 12.21% (27). Multi-drug resistance was noted in 57%. Higher
      resistance rate was noted among Gram negative bacilli for ampicillin (92.4%),
      cephalexin (82.46%), ciprofloxacin (68.42%), piperacillin (64.33%). Sensitivity
      to meropenem was 90.64% and amikacin was 76.61%. Gram positive bacteria showed
      high resistance to gentamicin (39.53%). Sensitivity to ampicillin was 86.05% and
      penicillin was 81.4%. Vancomycin and teicoplanin showed 100% sensitivity. From
      our study we conclude that E. coli, Klebsiella species and Enterococcus species
      are common pathogens infecting biliary tract. Poly-microbial infection and multi
      drug resistance warrants culture and sensitivity to guide antimicrobial therapy.
      We recommend combination of amikacin and ampicillin for empirical therapy at our
      institution.

PMID- 17001926
TI  - Diagnosis of leptospirosis and comparison of ELISA and MAT techniques.
AB  - Leptospirosis is perhaps the most common, most wide spread yet under diagnosed
      zoonosis in the world, Inada et al identified the causal agent in Japan in 1916.
      Microscopic agglutination test (MAT) developed initially by Martin and Pettit
      (1918) is the reference method that was successively done after ELISA test to
      evaluate and compare and make a reliable diagnosis. Blood samples were collected
      from August 2004 to September 2004 from hospitalized patients of South Gujarat
      region who were clinically suspected cases of leptospirosis according to WHO case
      definition. In our setup we separated the sera and carried out ELISA for
      detection of IgM antibodies and rest of the sera were stored at -20 degrees C. As
      we do not have the facility for performing MAT test in our centre, we personally
      carried these sera to Chennai for performing the MAT and identified the serovars
      prevalent in South Gujarat region. Out of 30 samples tested 16 samples (53.3%)
      were positive by ELISA and 12 samples (40%) were negative by ELISA. By MAT, 17
      samples (56.67%) were found positive and 13 samples (43.33%) were negative. 2
      samples were borderline by ELISA and these turned out to be negative by MAT.
      Cosidering MATas the gold standard the sensitivity of IgM ELISA in this study was
      88% and specificity 90.90%. We concluded that IgM ELISA is rapid test and its
      results are quite similar to MAT. The most common serovars isolated and
      identified are L. hebdomadis, L. pyrogenes, L. autumnalis and L. grippotyphosa in
      this part of the country.

PMID- 17001927
TI  - Pneumatosis intestinalis in post neonatal period.

PMID- 17001928
TI  - Assessment of prognosis of astrocytoma: is reticulin stain helpful?

PMID- 17001929
TI  - Association of ABO blood group system to intracranial tumours--a study from South
      India.

PMID- 17001930
TI  - Suture economy continued.

PMID- 17001931
TI  - Support for nurses.

PMID- 17001932
TI  - The sword of Damocles.

PMID- 17001933
TI  - Withdrawal of consent during surgery.

PMID- 17001934
TI  - Professional indemnity insurance: the NMC and Bar Council requirements.
AB  - In 2004, the Nursing and Midwifery Council (NMC) produced an updated version of
      its Code of Professional Conduct, entitled The NMC Code of Professional Conduct:
      Standards for Conduct, Performance and Ethics (2004). In part the aim of this
      latest version was to include for the first time certain groups of nurses.
      Specialist community public health nurses are named whereas the previous version
      (2002) referred to nurses and midwives only. However, the updated version also
      incorporates a new section--paragraph 9--which concentrates the registrant's mind
      towards the issue of insuring their practice. This article discusses the
      ramifications of this addition.

PMID- 17001935
TI  - Fool's gold or real gold?
AB  - The term evidence-based practice is not new. For over twenty years the debate has
      been ongoing about how to make it happen. To practice within an evidence base,
      practitioners must determine if the evidence available is relevant for the
      particular patient (DiCenso et al 1998). This article aims to contextualise,
      clarify and explore the meaning of evidence-based practice for perioperative
      practitioners and, through introducing two models, identify and categorise
      sources of evidence to base practice on.

PMID- 17001936
TI  - What is the 'nurse' in nurse anaesthetist? A policy and literature review.
AB  - External forces have had a direct and indirect impact on the role of the nurse.
      Key policy initiatives have been central to changes in administration. With
      management reorganisation and technical developments at the forefront of
      successive governments' economic and social policy, the nursing role has become
      diversified and increasingly specialised with perioperative practice developing
      as a consequence.

PMID- 17001937
TI  - Sickle cell disease in the perioperative setting.
AB  - This article explores Sickle Cell Disease and Sickle Cell Trait. These are
      hereditary conditions that affect thousands of people in the UK and abroad. The
      disease tends to occur in people of Afro-Caribbean or Mediterranean descent. The
      specific Pre-, Peri- and postoperative care of affected patients is examined.

PMID- 17001938
TI  - Operating department support level 2 NVQ: Some perceptions.
AB  - New roles for support staff are emerging and registered practitioners are now
      being asked to devolve key aspects of patient care. This study explores some of
      the background issues relating to these developments and provides evidence
      regarding the inevitability but also benefits, if managed well, of these changes.
      The experience of both support staff who have undertaken the Operating Department
      Support National Vocational Qualification Level 2 (ODS NVQ) and their managers
      was examined using a phenomenological approach. Data was obtained on the
      perceived value of this qualification and training and how it affected the
      working lives and career development of support staff.

PMID- 17001939
TI  - Patients' perceptions of the impact of treatments and products on their
      experience of leg ulcer pain.
AB  - OBJECTIVE: Very little research has explored patients' experience of pain with
      different cleansing agents and dressings. We therefore undertook a longitudinal
      study of their impact on leg ulcer pain. METHOD: Patients with leg ulcers
      referred to community nurses were eligible to participate. They were followed up
      for six months, completing questionnaires about the impact on pain of each wound
      treatment used. A treatment episode was defined as the use of a wound cleansing
      agent, primary dressing and bandages. When one aspect of treatment changed, a new
      treatment episode began. RESULTS: There were 210 treatment episodes for 96 leg
      ulcer patients. In 206 episodes cleansing agents were used. Cleansing caused pain
      in 22% of episodes and relieved pain in 27%. Of the five most commonly used
      dressing types, low-adherent dressings were the least likely to cause pain. Only
      56% of patients were able to tolerate full compression bandaging and pain was the
      most common reason for non-compliance. CONCLUSION: A substantial proportion of
      patients felt that leg ulcer treatments caused pain. A greater emphasis on the
      impact of treatment on pain and healing is warranted both clinically and in
      research.

PMID- 17001940
TI  - The concept of concordance and its relation to leg ulcer management.

PMID- 17001941
TI  - Looking back over a Scholarship year that is producing results.

PMID- 17001942
TI  - Overview of current practice and future trends in the evaluation of dressings for
      malodorous wounds.

PMID- 17001943
TI  - A cost-effectiveness analysis of two community models of care for patients with
      venous leg ulcers.
AB  - AIM: To conduct a cost-effectiveness analysis based on data from a randomised
      controlled trial comparing traditional community home nursing with a community
      Leg Club model for chronic venous leg ulcer management in the south-east
      metropolitan area of Queensland, Australia. METHOD: Participants were randomised
      to the Leg Club (n=28) or home visits (n=28). Data were obtained on
      resources/related costs incurred by the service provider, clients and carers, and
      the community. RESULTS: From the collective perspective (service provider,
      clients and carers, and the community), at six months the incremental cost per
      healed ulcer was dollars AU515 (Euros 318) and the incremental cost per reduced
      pain score was dollars AU322 (Euros 199). For the service provider, Leg Club
      intervention resulted in cost savings and better health effects when compared
      with home nursing. CONCLUSION: On both clinical and economic grounds, the Leg
      Club model appears to be more cost-effective than traditional home nursing for
      the treatment of chronic venous leg ulcers. However, clients and the local
      community contribute substantial financial and in-kind support to the operation
      of both services.

PMID- 17001945
TI  - Comparison of TNP therapy applications.

PMID- 17001944
TI  - Use of topical negative pressure with a lipidocolloid dressing: results of a
      clinical evaluation.
AB  - OBJECTIVE: To evaluate the protection and acceptability of Urgotul wound dressing
      in the local management of acute or chronic wounds receiving topical negative
      pressure (TNP) therapy. METHOD: This was a prospective multicentre non
      comparative open-label trial. At each dressing change the investigating physician
      clinically evaluated and photographed the wound. Planimetric measurement was
      undertaken and wound depth was assessed at the start and end of the treatment.
      Follow-up was undertaken until deemed clinically unnecessary by the investigator.
      RESULTS: Sixty-six patients were included (42 acute wounds and 24 chronic wounds)
      and followed up for an average of 17 days. Dressing changes were deemed entirely
      painless in 52% of cases (compared with 18% at baseline) and pain between two
      consecutive dressing changes was absent in 66% of cases (34% at baseline).
      Removal of the TNP-interface dressing combination was considered'very easy' or
      'easy' in 94% of cases and adherence to the wound was recorded as 'absent' in
      88%. On average, the dressings were changed every 3.8 +/- 1.1 days (all wounds
      were considered), and wound area and depth were reduced by 19% and 54%
      respectively by the end of the follow-up period. CONCLUSION: Use of the interface
      dressing in combination with TNP substantially reduced the pain caused by
      dressing changes. It therefore makes more acceptable the use of this technique,
      which aims to optimise the management of wounds that are sometimes considered to
      be in a therapeutic impasse.

PMID- 17001947
TI  - Use of a protease-modulating matrix dressing on a non-healing tendo-Achilles
      surgical wound.

PMID- 17001946
TI  - Diabetic foot ulcers in Cameroon: can microflora prevalence inform probabilistic
      antibiotic treatment?
AB  - OBJECTIVE: To determine the clinical features, regularly associated
      microorganisms and their susceptibility to antibiotics, and the clinical outcomes
      of foot ulcers in patients with diabetes at the Yaounde Central Hospital,
      Cameroon. METHOD: A retrospective analysis of routinely collected hospital data,
      and data validation by survey of clinical notes was conducted from November 1999
      to October 2002 for adult diabetic patients with foot ulcers. Clinical data were
      recorded for each patient, followed by a record of microbiological investigations
      where available. RESULTS: Of 503 patients with diabetes admitted during the study
      period, 54 (10.7%) had foot ulcers. Male subject represented 66.7% of this
      population. The mean age of the study population was 59.66 +/- 1.52 years. The
      foot ulcer led to the diagnosis of diabetes in six patients in whom the condition
      was previously unidentified. Of the 54 patients with foot ulcers, nine (16.7%)
      were selected for surgery and the remaining 45 were managed conservatively.
      Microbiological investigations were available for 21 patients. Proteus mirabilis
      was the most frequent microorganism yielded, and was regularly associated with
      Staphylococcus aureus. All the microorganisms isolated showed high sensitivity to
      second-generation quinolone antibiotics and were regularly sensitive to
      aminoglycoside antibiotics. Nine (16.7%) patients died and seven (13%) were
      discharged at their own request. CONCLUSION: The mortality rate among our
      diabetic patients with foot ulcers is high and the combination of second
      generation quinolone and aminoglycoside antibiotics can be proposed as a
      probabilistic antibiotic approach to treating foot infection.

PMID- 17001949
TI  - Guaranteed certified. CCHIT announces its first wave of certifications in the
      outpatient arena.

PMID- 17001948
TI  - A review of the use of a dermal skin substitute in burns care.

PMID- 17001950
TI  - NHIN gets technical. Stakeholders review NHIN prototypes in the first meeting of
      its kind in Bethesda, MD.

PMID- 17001951
TI  - Surgery, safety and IT. Care quality, efficiency and integration emerge as
      ongoing themes in surgery IT.

PMID- 17001952
TI  - Two-year planner. Healthcare users share upcoming plans and projects, as well as
      their take on the changing industry.

PMID- 17001953
TI  - QIOs get down to business. Quality improvement organizations work with doctors on
      IT adoption, as Congress takes a closer look.

PMID- 17001954
TI  - HITSP working to harmonize. The national data exchange group is making tough
      decisions to provide the industry with a sound set of standards.

PMID- 17001955
TI  - Against all odds. Political unrest creates unique challenges for healthcare
      organizations in regions of strife.

PMID- 17001957
TI  - Able to adapt. Ray Gensinger Jr.'s work implementing an EMR solution took him
      from the build to the buy.

PMID- 17001956
TI  - From a cellular level.

PMID- 17001958
TI  - Pushing the envelope. Leading projects focused on standards development and data
      sharing are among John Halamka's many credits.

PMID- 17001959
TI  - Culture shock. Spencer Hamons has changed the way IT operates at San Luis Valley
      Regional Medical Center.

PMID- 17001960
TI  - Courage under fire. Carl Hendricks is working to make sure soldiers get the best
      healthcare that technology can provide.

PMID- 17001961
TI  - Targeting IT. Jerome Hyzy's rapid response to patient concerns is making waves.

PMID- 17001962
TI  - Dream team. Glenn Miller and Robert Rubeck have been spreading health services
      access across the Great Plains.

PMID- 17001963
TI  - Creating a digital hospital. Tanya Townsend of Saint Clare's Hospital has worked
      hard to go digital.

PMID- 17001964
TI  - Right patient, right dose... Medication management is getting an IT makeover at
      safety-conscious healthcare organizations.

PMID- 17001965
TI  - Simulate for success. Sentara Healthcare uses simulation to get a complex HR
      portal right the first time.

PMID- 17001966
TI  - Chartless in memphis. Campbell Clinic Orthopaedics embraced an EHR to escape
      paper-based patient charting.

PMID- 17001967
TI  - Role playing. Busy medical staff input was invaluable to Mid-Atlantic Hospital in
      reengineering access to information.

PMID- 17001968
TI  - Beating diabetes. What could New York City's new program mean for you in the long
      run?

PMID- 17001969
TI  - Talking points. New technologies overcome delay, jitter and packet loss to ensure
      reliable VolP services across the data network.

PMID- 17001970
TI  - I've got the power. Intelligent grid-based storage is coming to healthcare,
      offering a reliable, cost-effective approach to storage needs.

PMID- 17001971
TI  - Handheld health. UHC is providing residents with Palm handhelds to stay
      competitive and enhance care.

PMID- 17001972
TI  - Prepping for pandemonium. Indian Health funds an emergency management system to
      save money and lives.

PMID- 17001973
TI  - Feature selection using a piecewise linear network.
AB  - We present an efficient feature selection algorithm for the general regression
      problem, which utilizes a piecewise linear orthonormal least squares (OLS)
      procedure. The algorithm 1) determines an appropriate piecewise linear network
      (PLN) model for the given data set, 2) applies the OLS procedure to the PLN
      model, and 3) searches for useful feature subsets using a floating search
      algorithm. The floating search prevents the "nesting effect." The proposed
      algorithm is computationally very efficient because only one data pass is
      required. Several examples are given to demonstrate the effectiveness of the
      proposed algorithm.

PMID- 17001974
TI  - On adaptive learning rate that guarantees convergence in feedforward networks.
AB  - This paper investigates new learning algorithms (LF I and LF II) based on
      Lyapunov function for the training of feedforward neural networks. It is observed
      that such algorithms have interesting parallel with the popular backpropagation
      (BP) algorithm where the fixed learning rate is replaced by an adaptive learning
      rate computed using convergence theorem based on Lyapunov stability theory. LF
      II, a modified version of LF I, has been introduced with an aim to avoid local
      minima. This modification also helps in improving the convergence speed in some
      cases. Conditions for achieving global minimum for these kind of algorithms have
      been studied in detail. The performances of the proposed algorithms are compared
      with BP algorithm and extended Kalman filtering (EKF) on three bench-mark
      function approximation problems: XOR, 3-bit parity, and 8-3 encoder. The
      comparisons are made in terms of number of learning iterations and computational
      time required for convergence. It is found that the proposed algorithms (LF I and
      II) are much faster in convergence than other two algorithms to attain same
      accuracy. Finally, the comparison is made on a complex two-dimensional (2-D)
      Gabor function and effect of adaptive learning rate for faster convergence is
      verified. In a nutshell, the investigations made in this paper help us better
      understand the learning procedure of feedforward neural networks in terms of
      adaptive learning rate, convergence speed, and local minima.

PMID- 17001975
TI  - Generalized core vector machines.
AB  - Kernel methods, such as the support vector machine (SVM), are often formulated as
      quadratic programming (QP) problems. However, given m training patterns, a naive
      implementation of the QP solver takes O(m3) training time and at least O(m2)
      space. Hence, scaling up these QPs is a major stumbling block in applying kernel
      methods on very large data sets, and a replacement of the naive method for
      finding the QP solutions is highly desirable. Recently, by using approximation
      algorithms for the minimum enclosing ball (MEB) problem, we proposed the core
      vector machine (CVM) algorithm that is much faster and can handle much larger
      data sets than existing SVM implementations. However, the CVM can only be used
      with certain kernel functions and kernel methods. For example, the very popular
      support vector regression (SVR) cannot be used with the CVM. In this paper, we
      introduce the center-constrained MEB problem and subsequently extend the CVM
      algorithm. The generalized CVM algorithm can now be used with any
      linear/nonlinear kernel and can also be applied to kernel methods such as SVR and
      the ranking SVM. Moreover, like the original CVM, its asymptotic time complexity
      is again linear in m and its space complexity is independent of m. Experiments
      show that the generalized CVM has comparable performance with state-of-the-art
      SVM and SVR implementations, but is faster and produces fewer support vectors on
      very large data sets.

PMID- 17001976
TI  - Multiperiodicity of discrete-time delayed neural networks evoked by periodic
      external inputs.
AB  - In this paper, the multiperiodicity of a general class of discrete-time delayed
      neural networks (DTDNNs) is formulated and studied. Several sufficient conditions
      are obtained to ensure n-neuron DTDNNs can have 2n periodic orbits and these
      periodic orbits are locally attractive. In addition, we give the conditions for a
      periodic orbit to be locally or globally attractive when the periodic orbit
      locates in a designated region. As two typical representatives, the Hopfield
      neural network and the cellular neural network are examined in detail. These
      conditions improve and extend the existing stability results in the literature.
      Simulations results are also discussed in three illustrative examples.

PMID- 17001977
TI  - Global exponential stability of multitime scale competitive neural networks with
      nonsmooth functions.
AB  - In this paper, we study the global exponential stability of a multitime scale
      competitive neural network model with nonsmooth functions, which models a
      literally inhibited neural network with unsupervised Hebbian learning. The
      network has two types of state variables, one corresponds to the fast neural
      activity and another to the slow unsupervised modification of connection weights.
      Based on the nonsmooth analysis techniques, we prove the existence and uniqueness
      of equilibrium for the system and establish some new theoretical conditions
      ensuring global exponential stability of the unique equilibrium of the neural
      network. Numerical simulations are conducted to illustrate the effectiveness of
      the derived conditions in characterizing stability regions of the neural network.

PMID- 17001978
TI  - Associative memory design using support vector machines.
AB  - The relation existing between support vector machines (SVMs) and recurrent
      associative memories is investigated. The design of associative memories based on
      the generalized brain-state-in-a-box (GBSB) neural model is formulated as a set
      of independent classification tasks which can be efficiently solved by standard
      software packages for SVM learning. Some properties of the networks designed in
      this way are evidenced, like the fact that surprisingly they follow a generalized
      Hebb's law. The performance of the SVM approach is compared to existing methods
      with nonsymmetric connections, by some design examples.

PMID- 17001979
TI  - Wavelet adaptive backstepping control for a class of nonlinear systems.
AB  - This paper proposes a wavelet adaptive backstepping control (WABC) system for a
      class of second-order nonlinear systems. The WABC comprises a neural backstepping
      controller and a robust controller. The neural backstepping controller containing
      a wavelet neural network (WNN) identifier is the principal controller, and the
      robust controller is designed to achieve L2 tracking performance with desired
      attenuation level. Since the WNN uses wavelet functions, its learning capability
      is superior to the conventional neural network for system identification.
      Moreover, the adaptation laws of the control system are derived in the sense of
      Lyapunov function and Barbalat's lemma, thus the system can be guaranteed to be
      asymptotically stable. The proposed WABC is applied to two nonlinear systems, a
      chaotic system and a wing-rock motion system to illustrate its effectiveness.
      Simulation results verify that the proposed WABC can achieve favorable tracking
      performance by incorporating of WNN identification, adaptive backstepping
      control, and L2 robust control techniques.

PMID- 17001980
TI  - Analysis of artificial neural networks for pattern-based adaptive control.
AB  - Adaptive pattern-based control strategies adapt their parameters from an analysis
      of response patterns exhibited by the system. This work presents an analysis of a
      class of artificial neural network (ANN) pattern-based adaptive control. It
      provides conditions under which the adaptive algorithm will converge, and it also
      characterizes the closed-loop stability properties. In addition, a method for
      monitoring the adaptation is also proposed. Several simulation examples
      illustrate our findings.

PMID- 17001981
TI  - Accuracy/diversity and ensemble MLP classifier design.
AB  - The difficulties of tuning parameters of multilayer perceptrons (MLP) classifiers
      are well known. In this paper, a measure is described that is capable of
      predicting the number of classifier training epochs for achieving optimal
      performance in an ensemble of MLP classifiers. The measure is computed between
      pairs of patterns on the training data and is based on a spectral representation
      of a Boolean function. This representation characterizes the mapping from
      classifier decisions to target label and allows accuracy and diversity to be
      incorporated within a single measure. Results on many benchmark problems,
      including the Olivetti Research Laboratory (ORL) face database demonstrate that
      the measure is well correlated with base-classifier test error, and may be used
      to predict the optimal number of training epochs. While correlation with ensemble
      test error is not quite as strong, it is shown in this paper that the measure may
      be used to predict number of epochs for optimal ensemble performance. Although
      the technique is only applicable to two-class problems, it is extended here to
      multiclass through output coding. For the output-coding technique, a random code
      matrix is shown to give better performance than one-per-class code, even when the
      base classifier is well-tuned.

PMID- 17001982
TI  - Study of a fast discriminative training algorithm for pattern recognition.
AB  - Discriminative training refers to an approach to pattern recognition based on
      direct minimization of a cost function commensurate with the performance of the
      recognition system. This is in contrast to the procedure of probability
      distribution estimation as conventionally required in Bayes' formulation of the
      statistical pattern recognition problem. Currently, most discriminative training
      algorithms for nonlinear classifier designs are based on gradient-descent (GD)
      methods for cost minimization. These algorithms are easy to derive and effective
      in practice, but are slow in training speed and have difficulty selecting the
      learning rates. To address the problem, we present our study on a fast
      discriminative training algorithm. The algorithm initializes the parameters by
      the expectation-maximization (EM) algorithm, and then uses a set of closed-form
      formulas derived in this paper to further optimize a proposed objective of
      minimizing error rate. Experiments in speech applications show that the algorithm
      provides better recognition accuracy in a fewer iterations than the EM algorithm
      and a neural network trained by hundreds of GD iterations. Although some
      convergent properties need further research, the proposed objective and derived
      formulas can benefit further study of the problem.

PMID- 17001983
TI  - Training reformulated radial basis function neural networks capable of
      identifying uncertainty in data classification.
AB  - This paper introduces a learning algorithm that can be used for training
      reformulated radial basis function neural networks (RBFNNs) capable of
      identifying uncertainty in data classification. This learning algorithm trains a
      special class of reformulated RBFNNs, known as cosine RBFNNs, by updating
      selected adjustable parameters to minimize the class-conditional variances at the
      outputs of their radial basis functions (RBFs). The experiments verify that
      quantum neural networks (QNNs) and cosine RBFNNs trained by the proposed learning
      algorithm are capable of identifying uncertainty in data classification, a
      property that is not shared by cosine RBFNNs trained by the original learning
      algorithm and conventional feed-forward neural networks (FFNNs). Finally, this
      study leads to a simple classification strategy that can be used to improve the
      classification accuracy of QNNs and cosine RBFNNs by rejecting ambiguous feature
      vectors based on their responses.

PMID- 17001984
TI  - Prune-able fuzzy ART neural architecture for robot map learning and navigation in
      dynamic environments.
AB  - Mobile robots must be able to build their own maps to navigate in unknown worlds.
      Expanding a previously proposed method based on the fuzzy ART neural architecture
      (FARTNA), this paper introduces a new online method for learning maps of unknown
      dynamic worlds. For this purpose the new Prune-able fuzzy adaptive resonance
      theory neural architecture (PAFARTNA) is introduced. It extends the FARTNA self
      organizing neural network with novel mechanisms that provide important dynamic
      adaptation capabilities. Relevant PAFARTNA properties are formulated and
      demonstrated. A method is proposed for the perception of object removals, and
      then integrated with PAFARTNA. The proposed methods are integrated into a
      navigation architecture. With the new navigation architecture the mobile robot is
      able to navigate in changing worlds, and a degree of optimality is maintained,
      associated to a shortest path planning approach implemented in real-time over the
      underlying global world model. Experimental results obtained with a Nomad 200
      robot are presented demonstrating the feasibility and effectiveness of the
      proposed methods.

PMID- 17001985
TI  - A Hopfield neural network for image change detection.
AB  - This paper outlines an optimization relaxation approach based on the analog
      Hopfield neural network (HNN) for solving the image change detection problem
      between two images. A difference image is obtained by subtracting pixel by pixel
      both images. The network topology is built so that each pixel in the difference
      image is a node in the network. Each node is characterized by its state, which
      determines if a pixel has changed. An energy function is derived, so that the
      network converges to stable states. The analog Hopfield's model allows each node
      to take on analog state values. Unlike most widely used approaches, where binary
      labels (changed/unchanged) are assigned to each pixel, the analog property
      provides the strength of the change. The main contribution of this paper is
      reflected in the customization of the analog Hopfield neural network to derive an
      automatic image change detection approach. When a pixel is being processed, some
      existing image change detection procedures consider only interpixel relations on
      its neighborhood. The main drawback of such approaches is the labeling of this
      pixel as changed or unchanged according to the information supplied by its
      neighbors, where its own information is ignored. The Hopfield model overcomes
      this drawback and for each pixel allows a tradeoff between the influence of its
      neighborhood and its own criterion. This is mapped under the energy function to
      be minimized. The performance of the proposed method is illustrated by
      comparative analysis against some existing image change detection methods.

PMID- 17001986
TI  - Efficient variant of algorithm FastICA for independent component analysis
      attaining the Cramer-Rao lower bound.
AB  - FastICA is one of the most popular algorithms for independent component analysis
      (ICA), demixing a set of statistically independent sources that have been mixed
      linearly. A key question is how accurate the method is for finite data samples.
      We propose an improved version of the FastICA algorithm which is asymptotically
      efficient, i.e., its accuracy given by the residual error variance attains the
      Cramer-Rao lower bound (CRB). The error is thus as small as possible. This result
      is rigorously proven under the assumption that the probability distribution of
      the independent signal components belongs to the class of generalized Gaussian
      (GG) distributions with parameter alpha, denoted GG(alpha) for alpha > 2. We name
      the algorithm efficient FastICA (EFICA). Computational complexity of a Matlab
      implementation of the algorithm is shown to be only slightly (about three times)
      higher than that of the standard symmetric FastICA. Simulations corroborate these
      claims and show superior performance of the algorithm compared with algorithm
      JADE of Cardoso and Souloumiac and nonparametric ICA of Boscolo et al. on
      separating sources with distribution GG (alpha) with arbitrary alpha, as well as
      on sources with bimodal distribution, and a good performance in separating
      linearly mixed speech signals.

PMID- 17001987
TI  - A neural network approach to dynamic task assignment of multirobots.
AB  - In this paper, a neural network approach to task assignment, based on a self
      organizing map (SOM), is proposed for a multirobot system in dynamic environments
      subject to uncertainties. It is capable of dynamically controlling a group of
      mobile robots to achieve multiple tasks at different locations, so that the
      desired number of robots will arrive at every target location from arbitrary
      initial locations. In the proposed approach, the robot motion planning is
      integrated with the task assignment, thus the robots start to move once the
      overall task is given. The robot navigation can be dynamically adjusted to
      guarantee that each target location has the desired number of robots, even under
      uncertainties such as when some robots break down. The proposed approach is
      capable of dealing with changing environments. The effectiveness and efficiency
      of the proposed approach are demonstrated by simulation studies.

PMID- 17001988
TI  - Accurate and fast off and online fuzzy ARTMAP-based image classification with
      application to genetic abnormality diagnosis.
AB  - We propose and investigate the fuzzy ARTMAP neural network in off and online
      classification of fluorescence in situ hybridization image signals enabling
      clinical diagnosis of numerical genetic abnormalities. We evaluate the
      classification task (detecting a several abnormalities separately or
      simultaneously), classifier paradigm (monolithic or hierarchical), ordering
      strategy for the training patterns (averaging or voting), training mode (for one
      epoch, with validation or until completion) and model sensitivity to parameters.
      We find the fuzzy ARTMAP accurate in accomplishing both tasks requiring only very
      few training epochs. Also, selecting a training ordering by voting is more
      precise than if averaging over orderings. If trained for only one epoch, the
      fuzzy ARTMAP provides fast, yet stable and accurate learning as well as
      insensitivity to model complexity. Early stop of training using a validation set
      reduces the fuzzy ARTMAP complexity as for other machine learning models but
      cannot improve accuracy beyond that achieved when training is completed. Compared
      to other machine learning models, the fuzzy ARTMAP does not loose but gain
      accuracy when overtrained, although increasing its number of categories. Learned
      incrementally, the fuzzy ARTMAP reaches its ultimate accuracy very fast obtaining
      most of its data representation capability and accuracy by using only a few
      examples. Finally, the fuzzy ARTMAP accuracy for this domain is comparable with
      those of the multilayer perceptron and support vector machine and superior to
      those of the naive Bayesian and linear classifiers.

PMID- 17001989
TI  - Stock trading using RSPOP: a novel rough set-based neuro-fuzzy approach.
AB  - This paper investigates the method of forecasting stock price difference on
      artificially generated price series data using neuro-fuzzy systems and neural
      networks. As trading profits is more important to an investor than statistical
      performance, this paper proposes a novel rough set-based neuro-fuzzy stock
      trading decision model called stock trading using rough set-based pseudo outer
      product (RSPOP) which synergizes the price difference forecast method with a
      forecast bottleneck free trading decision model. The proposed stock trading with
      forecast model uses the pseudo outer-product based fuzzy neural network using the
      compositional rule of inference [POPFNN-CRI(S)] with fuzzy rules identified using
      the RSPOP algorithm as the underlying predictor model and simple moving average
      trading rules in the stock trading decision model. Experimental results using the
      proposed stock trading with RSPOP forecast model on real world stock market data
      are presented. Trading profits in terms of portfolio end values obtained are
      benchmarked against stock trading with dynamic evolving neural-fuzzy inference
      system (DENFIS) forecast model, the stock trading without forecast model and the
      stock trading with ideal forecast model. Experimental results showed that the
      proposed model identified rules with greater interpretability and yielded
      significantly higher profits than the stock trading with DENFIS forecast model
      and the stock trading without forecast model.

PMID- 17001990
TI  - A convolutional neural network approach for objective video quality assessment.
AB  - This paper describes an application of neural networks in the field of objective
      measurement method designed to automatically assess the perceived quality of
      digital videos. This challenging issue aims to emulate human judgment and to
      replace very complex and time consuming subjective quality assessment. Several
      metrics have been proposed in literature to tackle this issue. They are based on
      a general framework that combines different stages, each of them addressing
      complex problems. The ambition of this paper is not to present a global perfect
      quality metric but rather to focus on an original way to use neural networks in
      such a framework in the context of reduced reference (RR) quality metric.
      Especially, we point out the interest of such a tool for combining features and
      pooling them in order to compute quality scores. The proposed approach solves
      some problems inherent to objective metrics that should predict subjective
      quality score obtained using the single stimulus continuous quality evaluation
      (SSCQE) method. This latter has been adopted by video quality expert group (VQEG)
      in its recently finalized reduced referenced and no reference (RRNR-TV) test
      plan. The originality of such approach compared to previous attempts to use
      neural networks for quality assessment, relies on the use of a convolutional
      neural network (CNN) that allows a continuous time scoring of the video.
      Objective features are extracted on a frame-by-frame basis on both the reference
      and the distorted sequences; they are derived from a perceptual-based
      representation and integrated along the temporal axis using a time-delay neural
      network (TDNN). Experiments conducted on different MPEG-2 videos, with bit rates
      ranging 2-6 Mb/s, show the effectiveness of the proposed approach to get a
      plausible model of temporal pooling from the human vision system (HVS) point of
      view. More specifically, a linear correlation criteria, between objective and
      subjective scoring, up to 0.92 has been obtained on a set of typical TV videos.

PMID- 17001991
TI  - Feed-forward support vector machine without multipliers.
AB  - In this letter, we propose a coordinate rotation digital computer (CORDIC)-like
      algorithm for computing the feed-forward phase of a support vector machine (SVM)
      in fixed-point arithmetic, using only shift and add operations and avoiding
      resource-consuming multiplications. This result is obtained thanks to a hardware
      friendly kernel, which greatly simplifies the SVM feed-forward phase computation
      and, at the same time, maintains good classification performance respect to the
      conventional Gaussian kernel.

PMID- 17001992
TI  - Analysis and simulation of a mixed-mode neuron architecture for sensor
      conditioning.
AB  - The design, analysis, and system simulation of an adaptive processor based on a
      current-mode mixed analog-digital circuit is presented. The processor consists of
      a mixed four-quadrant multiplier and a current conveyor that performs the
      nonlinearity. Schematics, circuit parameters, and a high-level model are shown.
      The results achieved when applying this processor model to conditioning several
      sensor types are discussed.

PMID- 17001993
TI  - Monitoring the formation of kernel-based topographic maps in a hybrid SOM-kMER
      model.
AB  - A new lattice disentangling monitoring algorithm for a hybrid self-organizing map
      kernel-based maximum entropy learning rule (SOM-kMER) model is proposed. It aims
      to overcome topological defects owing to a rapid decrease of the neighborhood
      range over the finite running time in topographic map formation. The empirical
      results demonstrate that the proposed approach is able to accelerate the
      formation of a topographic map and, at the same time, to simplify the monitoring
      procedure.

PMID- 17001994
TI  - Improvements of complex-valued Hopfield associative memory by using generalized
      projection rules.
AB  - In this letter, new design methods for the complex-valued multistate Hopfield
      associative memories (CVHAMs) are presented. We show that the well-known
      projection rule proposed by Personnaz et al. can be generalized to complex domain
      such that the weight matrix of the CVHAM can be designed by using a simple and
      effective method. The stability of the proposed CVHAM is analyzed by using energy
      function approach which shows that in synchronous update mode the proposed model
      is guaranteed to converge to a fixed point from any given initial state.
      Moreover, the projection geometry of the generalized projection rule (GPR) is
      discussed. In order to enhance the recall capability, a strategy of eliminating
      the spurious memories is also reported. The validity and the performance of the
      proposed methods are investigated by computer simulation.

PMID- 17001995
TI  - Disaster planning: learning from the past, preparing for the future.

PMID- 17001996
TI  - Self-care management in adults undergoing hemodialysis.
AB  - The research literature on self-care management for adults with end stage renal
      disease being treated with hemodialysis was reviewed to ascertain the current
      state of knowledge, identify gaps, and propose future research. Sixty-four
      studies were reviewed. Many studies focused on compliance and whether subjects
      were meeting predetermined values of outcome variables set by professionals. Self
      care management of ESRD is multidimensional and warrants further research from
      the client professional, and health care system perspectives.

PMID- 17001997
TI  - Patients' perceptions concerning choice among renal replacement therapies: a
      pilot study.
AB  - PURPOSE: The purposes of this pilot study were to determine which replacement
      therapy group would be most appropriate for exploring the concept of choice and
      to refine the research question. METHODS: This exploratory, descriptive study
      used a phenomenological method. RESULTS: Four themes were derived: (1)
      uncertainty of long-term health, (2) lack of choice, (3) no memory of making a
      choice, and (4) lack of information about renal replacement therapies.
      CONCLUSIONS: No participant remembered actually making a choice regarding their
      renal replacement therapies.

PMID- 17001998
TI  - Sampling for international normalized ratios in patients on hemodialysis with
      central venous catheters.
AB  - The primary objectives of this study were to evaluate the effect of varying
      heparin concentrations on International Normalized Ratio values and to assess the
      accuracy of these values deter mined through the arterial line of the dialysis
      circuit Twenty-two patients on hemodialysis with central venous catheters were
      studied After a peripheral venipuncture, timed samples from the arterial line of
      the hemodialysis circuit were obtained after dialysis was initiated and prior to
      initiating heparin. Assays for coagulation parameters were performed. There was
      no signifcant difference in any coagulation parameter measured from the arterial
      line samples compared to the venipuncture samples. Serial heparin dilutions in
      vitro demonstrated that residual amounts of heparin in the central venous
      catheter may falsely elevate International Normalized Ratio values. This study
      demonstrates that accurate International Normalized Ratio values in patients on
      hemodialysis with heparinized central venous catheters can be obtained ericiently
      and cost-effectively from the arterial line within 1 minute of dialysis
      initiation.

PMID- 17001999
TI  - Management of pediatric patients with chronic kidney disease.
AB  - Chronic kidney disease in children is associated with complications that require
      nursing interventions in both the inpatient and outpatient settings. Given the
      progressive nature of the disease and the complexity of the treatment regimen, it
      is important that nurses be comfortable implementing acute and preventive care
      strategies and facilitating the coordination of care. In addition, the need for
      multiple therapies can be distressing for patients and theirfamilies, further
      supporting the role of the nurse in patient and family education and decision
      making regarding the plan of care. In this review, we discuss the pertinent
      issues of pediatric chronic kidney disease in the context of a case study to
      promote better understanding of real-world nursing practice.

PMID- 17002000
TI  - The KDOQI clinical practice guidelines and clinical practice recommendations for
      treating anemia in patients with chronic kidney disease: implications for nurses.
AB  - The National Kidney Foundation Kidney Disease Outcomes Quality Initiative
      recently published revised clinical practice guidelines and recommendations for
      the treatment of anemia. This article provides an overview of the new guidelines
      and recommendations, with a focus on the hemoglobin treatment range, iron status,
      use of erythropoiesis-stimulating agents, and adjuvant therapies.

PMID- 17002001
TI  - Adjusting i.v. iron and EPO doses in patients on hemodialysis prior to continuing
      surgery: can we protect our patients education from iron-deficiency anemia?
AB  - Ongoing blood loss and iron-deficiency anemia are common problems in patients on
      hemodialysis; therefore, nephrology clinicians are particularly concerned with
      their patients who are scheduled for surgery Surgery can cause significant blood
      and iron losses, thereby worsening their preexisting anemia. However, patients on
      hemodialysis can be effectively treated preoperatively by adjusting their
      continued doses of intravenous (i.v.) iron and recombinant human erythropoietin
      (EPO) therapy, based on expected blood and iron losses. This valuable strategy
      can help improve surgical and anemia outcomes as well as decrease EPO
      requirements and the need for transfusions. This article examines the use of IV
      iron and EPO therapy as preventive therapy for anemia in patients on hemodialysis
      prior to invasive surgical procedures, illustrated with an experience from a
      dialysis unit and patient case studies.

PMID- 17002002
TI  - Hemodialysis special interest group networking session: fluid management: moving
      and removing fluid during hemodialysis.

PMID- 17002004
TI  - Fistulae are first at Kansas dialysis services.

PMID- 17002003
TI  - Should dialysis be offered to all patients? Some patients should not be given the
      option of dialysis.

PMID- 17002005
TI  - Weight management in patients on peritoneal dialysis.
AB  - In summary, patients on PD, along with their health care providers, can be taught
      tools to manage weight. These techniques include, but are not limited to,
      judicious use of dialysis solution to provide adequate dialysis and
      ultrafiltration with the least exposure to glucose, careful attention to diet
      including salt and calories consumed, and physical activity.

PMID- 17002006
TI  - Sexuality: everything you might be afraid to ask but patients need to know.

PMID- 17002007
TI  - How do you break the ice when discussing sexuality issues with patients with
      cancer?

PMID- 17002009
TI  - Set to stun.

PMID- 17002010
TI  - Limiting self harm.

PMID- 17002011
TI  - Genetics in emergency care.

PMID- 17002012
TI  - Practice makes perfect. Management of pulled elbows.

PMID- 17002013
TI  - Using handheld pocket computers in a wireless telemedicine system.

PMID- 17002014
TI  - Treating leg ulcers.

PMID- 17002015
TI  - Developing a new intravenous therapy service: part 2.

PMID- 17002016
TI  - Board's eye view.

PMID- 17002017
TI  - [Cardial fibrosis and the functional activity of leukocytes in patients with
      essential arterial hypertension].
AB  - The study revealed an increase in the serum levels of TGF-beta1 and the N
      terminal peptide procollagen type III in patients with essential arterial
      hypertension (EAH), as well as an association between this increase and the
      duration of the disease, mean day arterial pressure profile, and left ventricular
      hypertrophy. An increased leukocyte functional activity is associated with
      disturbances in left ventricular diastolic function and an increase in TGF-beta1
      serum concentration in EAH. The authors conclude that leukocytes participate in
      the development of myocardial hypertrophy and cardial fibrosis through the
      secretion of pro-inflammatory cytokines and peptide growth factors within the
      process of their activation.

PMID- 17002018
TI  - [The results of quantitative cytological analysis of the structure of follicular
      thyroid tumors using computer and neural network technologies].
AB  - Artificial neural network is a complex system capable of gathering and
      synthesizing data and capable of learning using particular given parameters. This
      technology was applied to studying cytological diagnostics of thyroid diseases to
      differentiate between follicular cancer and follicular adenoma. A complex of
      quantitative cytological characteristics was used to describe cytological
      preparations by examples of known cytological diagnosis to train the neural
      network. Among offered cytological examples, 96% were recognized correctly during
      testing.

PMID- 17002019
TI  - [The role of oxygen free radicals in the mechanisms of local and distant ischemic
      myocardial preconditioning].
AB  - The phenomenon of ischemic preconditioning consists in increase in myocardial
      tolerance to ischemia after short periods of ischemia and reperfusion of the
      myocardium (local preconditioning) or a distant organ (distant preconditioning).
      This study is dedicated to the role of oxygen free radicals (OFR) in the
      mechanisms of preconditioning; pharmacological inhibition of OFR with N-2
      mercaptopropionylglycin, a synthetic anti-oxidant, was used. Mouse experiments
      demonstrated a reduction in the infarction-limiting effect of local
      preconditioning as a result of OFR inhibiting. This confirms the hypothesis
      according to which OFR play an important role in the mechanisms of launching and
      mediating the protective effect of local preconditioning. On the contrary,
      application of the same dose of N2-mercaptopropionylglycin does not lead to a
      significant weakening of the infarction-limiting effect of distant
      preconditioning caused by 20 min of ischemia and 15 min of reperfusion of the
      small intestine. Thus, it is unlikely that OFR participate in the realization of
      the effect of distant preconditioning caused by small intestinal ischemia. The
      authors discuss hypothetic molecular mechanisms of distant myocardial
      preconditioning.

PMID- 17002020
TI  - [The forming of child and adolescent adaptability].
AB  - Adaptability is an ability of the organism to spend its functional reserve in
      order to keep the balance with the environment and then make up for the use of
      this reserve. The adaptation of a growing organism to the environment is an
      intersystem process. The condition of functional intersystem regulation and
      cardiac rhythm variability in particular, serve as indicators of child
      adaptability. Adaptability is formed under the influence of such biological
      factors as heredity, age, gender, health status, and such environmental ones as
      nutrition balance, quality of life, physical activity, day regimen, and learning
      conditions. The authors developed a conceptual model of interrelation between
      biological and environmental factors in the forming of child adaptability.

PMID- 17002021
TI  - [The role of clinical suicidology in the system of measures directed towards
      lowering early mortality and increasing population life span].
AB  - The level of early mortality has increased substantially in Russia within the
      last fifteen years, having exceeded the same parameter in developed countries and
      in the entire post-Soviet area. The second frequent reason for early mortality is
      a group of factors that includes accidents, suicides, murders, and other external
      causes. The proportion of suicides in this group is 45 to 50%. As a result, in
      the recent years the suicide rate in Russia has filled the second place in the
      world. The authors of this article analyze the suicide rate in different Russian
      regions, distinguishing between regions with the highest and lowest rate, and
      characterizing population risk factors of suicidal danger, a special place among
      which is filled by socioeconomic condition of the regions and the ethnic
      composition of their population. Increase of the effectiveness of suicide
      prevention depends on creation of adequate scientific basis, which clinical
      suicidology can become. The authors substantiate the necessity to distinguish
      suicidology as a separate field of clinical medicine, and formulate its
      definition, goals and objectives. Basing on the obtained results, the authors
      come to a conclusion on the medico-social importance of the development of
      clinical suicidology in lowering early mortality and increasing the country's
      population life span.

PMID- 17002022
TI  - [Variations of respiratory parameters in healthy men].
AB  - The subjects of the study were 656 healthy men living in the south of West
      Siberia, in whom the basic parameters of gas exchange, lung ventilation, static
      lung volumes, and bronchial permeability were measured. The significance and
      incidence of non-pathological changes in the system of external respiration were
      defined on the basis of statistical and cluster analysis of these parameters. The
      study shows that individuals with functional changes can be divided into four
      groups with different characteristics: 1. Steady mobilization of the reserve
      tissue of the respiratory parts of the lungs as a physiological defense reaction
      to unfavorable ecological factors; 2. An increased airiness of the respiratory
      tissue as a sign of a compensatory reaction directed towards maintaining gas
      homeostasis in frequent and prominent overload of the system of external
      respiration; 3. Steady hyperventilation as a direct functional response of the
      organism to the slowing down of oxygen mass transfer in the respiratory parts of
      the lungs; 4. Restriction of external respiration due to respiratory diseases in
      the past. Despite differences in the origin, all the studied functional changes
      have one common feature, i.e. their association with a decrease in external
      respiratory reserve; all of them should be considered pulmonological risk
      manifestations.

PMID- 17002023
TI  - [The epidemiological characteristics of tobacco smoking].
AB  - The author analyses the pattern of the occurrence and development of tobacco
      addiction among the city population of Samara. Analysis of the epidemiological
      features of tobacco smoking in Samara shows that its prevalence is quite high
      among both men and women, especially young ones. The prevalence of smoking
      depends on the level of education and family status; the proportion of smokers is
      the smallest among married people with higher education. These facts evidence the
      necessity of active anti-smoking preventive measures that would integrate efforts
      of the medical community and would be directed towards different social
      population groups.

PMID- 17002024
TI  - [Direct drug delivery to the brain].
AB  - The authors of the review discuss the present-day state of and promising
      approaches to directed delivery of biological agents into the brain. Special
      attention is drawn to micellar and liposomal transport through the blood-brain
      barrier (BBB) targeted by immunochemical vectors, such as native or hydrophobized
      antibodies to specific antigens located at the BBB or in the brain parenchyma.

PMID- 17002025
TI  - [New generation pharmaceuticals from milk of transgenic animals. The problem of
      isolation of biologically active proteins].
AB  - The authors of the review characterize the protein components of milk and adduce
      data on the expression of transgenic proteins in animal milk. Technological
      principles of purification of recombinant medicinal proteins from milk of
      transgenic animals are covered.

PMID- 17002026
TI  - Study finds tailored HIV program reduces risky sexual behaviors.

PMID- 17002027
TI  - Case report: differentiating artifact from true ventricular tachycardia.

PMID- 17002028
TI  - Transgender care resources for family physicians.

PMID- 17002029
TI  - Guidelines for the use of antibiotics in acute upper respiratory tract
      infections.
AB  - To help physicians with the appropriate use of antibiotics in children and adults
      with upper respiratory tract infection, a multidisciplinary team evaluated
      existing guidelines and summarized key practice points. Acute otitis media in
      children should be diagnosed only if there is abrupt onset, signs of middle ear
      effusion, and symptoms of inflammation. A period of observation without immediate
      use of antibiotics is an option for certain children. In patients with sinus
      infection, acute bacterial rhinosinusitis should be diagnosed and treated with
      antibiotics only if symptoms have not improved after 10 days or have worsened
      after five to seven days. In patients with sore throat, a diagnosis of group A
      beta-hemolytic streptococcus pharyngitis generally requires confirmation with
      rapid antigen testing, although other guidelines allow for empiric therapy if a
      validated clinical rule suggests a high likelihood of infection. Acute bronchitis
      in otherwise healthy adults should not be treated with antibiotics; delayed
      prescriptions may help ease patient fears and simultaneously reduce inappropriate
      use of antibiotics.

PMID- 17002030
TI  - Information from your family doctor. When antibiotics can help.

PMID- 17002031
TI  - Tight control of type 1 diabetes: recommendations for patients.
AB  - Tight control of blood glucose levels and risk factors for cardiovascular disease
      (e.g., hypertension, hypercholesterolemia) can substantially reduce the incidence
      of microvascular and macrovascular complications from type 1 diabetes. Physicians
      play an important role in helping patients make essential lifestyle changes to
      reduce the risk of these complications. Key recommendations that family
      physicians can give patients to optimize their outcomes include: take control of
      daily decisions regarding your health, focus on preventing and controlling risk
      factors for cardiovascular disease, tightly control your blood glucose level, be
      cognizant of potentially inaccurate blood glucose test results, use physiologic
      insulin replacement regimens, and learn how to manage and prevent hypoglycemia.

PMID- 17002032
TI  - Information from your family doctor. Type 1 diabetes: what you should know.

PMID- 17002033
TI  - Asymptomatic bacteriuria in adults.
AB  - A common dilemma in clinical medicine is whether to treat asymptomatic patients
      who present with bacteria in their urine. There are few scenarios in which
      antibiotic treatment of asymptomatic bacteruria has been shown to improve patient
      outcomes. Because of increasing antimicrobial resistance, it is important not to
      treat patients with asymptomatic bacteriuria unless there is evidence of
      potential benefit. Women who are pregnant should be screened for asymptomatic
      bacteriuria in the first trimester and treated, if positive. Treating
      asymptomatic bacteriuria in patients with diabetes, older persons, patients with
      or without indwelling catheters, or patients with spinal cord injuries has not
      been found to improve outcomes.

PMID- 17002034
TI  - Hemolytic uremic syndrome: an emerging health risk.
AB  - Hemolytic uremic syndrome is caused primarily by Shiga toxin-producing
      Escherichia coli O157:H7. The most common cause of acute renal failure in
      children, hemolytic uremic syndrome also can occur in adults. Characteristic
      features of the syndrome are microangiopathic anemia, thrombotic
      thrombocytopenia, and renal failure. Although the presentation of this syndrome
      is diverse, the classic prodromal illness is bloody diarrhea following ingestion
      of hamburger meat contaminated with E. coli O157:H7, the most common mode of
      infection in the United States. Children with hemolytic uremic syndrome generally
      present with gastroenteritis complaints (e.g., abdominal pain or tenderness,
      nausea or vomiting, fever, anemia); affected adults may be asymptomatic.
      Complications from hemolytic uremic syndrome can include intussusception, chronic
      renal failure, and seizures in severe cases. Because an incubation period of
      approximately one week occurs between the start of diarrhea and the onset of
      hemolytic uremic syndrome, physicians should maintain a high index of suspicion;
      early laboratory testing is important to diagnose and manage this syndrome.
      Obtaining a complete blood count and stool culture and performing Shiga toxin
      testing are the first of a series of tests that may help diagnose hemolytic
      uremic syndrome.

PMID- 17002035
TI  - Information from your family doctor. Hemolytic uremic syndrome.

PMID- 17002036
TI  - Predicting short-term risk of stroke after TIA.

PMID- 17002037
TI  - Screening for developmental dysplasia of the hip. (Quiz 1005-6).

PMID- 17002038
TI  - Pruritic rash in the intertriginous areas.

PMID- 17002039
TI  - [Nitric oxide and vascular effects of lipoproteins: cellular and molecular
      mechanisms].

PMID- 17002040
TI  - [Long-fragment DNA of blood plasma as one of the criteria of individual
      sensitivity to emotional stress and to cerebral ischemia].
AB  - Intravenous injection ofpolyethylenoxide WSR-301 reducing hydrodynamic blood
      resistance (Toms effect) improves gas exchange in the lungs and halved lethality
      of the animals with cerebral ischemia. The aim of the study was to establish
      whether free plasma DNA influences blood gases and lethality of the animals with
      brain ischemia. Common carotid arteries were ligated for 15 min in intact
      stressed and tested in the open field Wistar male rats, then some of the rats
      received intravenous solution of homologous long-fragment DNA (20x10(-6) g/ml of
      blood). Cerebral circulation, acid-base equilibrium, paO2, paCO2, asymptotic
      blood viscosity, plasmic concentration and length of DNA fragments in plasma,
      lethality and neurological status of the survivors were studied. It was found
      that long fragments of rat DNA show hydrodynamic Toms effect. In normal passive
      rats sensitive to cerebral ischemia part of plasm DNA is fragmented, gas
      composition and blood viscosity of blood is worse (p < 0.05) than in active
      animals. There is a direct correlation between the level of long-fragment DNA in
      plasm and paO2 (r = 0.55) and inverse--with paCO2 (r = -0.84). Intravenous
      injection of long-fragment DNA improved the course and reduced lethality of brain
      ischemia 2-3-fold. Thus, qualitative and quantitative characteristics of plasma
      circulating DNA are responsible for differences in blood gases in rats
      differently tolerable to cerebral ischemia and can serve as one of the criteria
      of individual sensitivity to it being essential in pathogenesis of ischemic
      stroke.

PMID- 17002041
TI  - [The role of changes in tissue redox-status in mechanism of paraneoplasia].
AB  - To specify mechanisms of paraneoplastic alterations of redox-status of tissues in
      experimental malignant tumor growth, we investigated electronic paramagnetic
      centers of blood, skeletal muscle and liver with electronic paramagnetic
      resonance (EPR) method. We also studied the concentration and activity of
      antioxidant enzymes. Our experiments on adult white male rats of mixed population
      with sarcoma C-45 and mice with Ehrlich carcinoma have shown that malignant tumor
      growth leads to enhanced lipid peroxidation (LPO): production of potent LPO
      promoters - Fe2+, Mn+2+, NO, ubiquinone; depression of antioxidant defence -
      reduced production of total ceruloplasmin, elevated blood levels of oxidized
      ceruloplasmin and enhanced catalase activity. It is suggested that malignant
      tumor growth is associated with marked paraneoplastic shifts in tissue redox
      potential. These alterations are involved in mechanisms of paraneoplastic changes
      of red cells, microhemocirculation and circulation intensity. All these
      interrelated processes result in generalized paraneoplastic hypoxia of the organs
      and tissues. Basing on our and literature data, we propose an original scheme of
      the mechanisms of paraneoplastic disorders of tissue redox-status,
      microcirculation and erythrocytes.

PMID- 17002042
TI  - [Esophagogastroimpedancemanometry in diagnosis of gastroesophageal reflux in
      patients with chemical burns of the stomach].
AB  - Esophagogastroimpedancemanometry conducted in 40 patients with chemical bums of
      the stomach (CBS) in acute and early postburn periods has revealed that CBS
      affect motor function of the cardia in 95% patients. This motor cardial
      dysfunction results in erosive and erosive-ulcerous reflux-esophagitis in 22.5%
      patients. Motor dysfunction of the cardia and esophagitis depends both on CBS
      severity and time since the trauma. Gastroesophageal reflux in CBS patients is
      triggered by intragastric hypertension accompanied with lowering of the
      esophageal-gastric pressure gradient provoking motor dysfunction of the esophagus
      and reduction of the esophageal clearance.

PMID- 17002043
TI  - [Specified mechanisms of action of preimmunisation with diphtherial anatoxin on
      myocardial pathology after critical care].
AB  - Chronic experiments for 5 weeks made in 41 mongrel adult dogs have shown that
      prevaccination with diphtheria antitoxin has a negative effect on myocardial and
      hemodynamic restoration after resustitation. The dogs have arrhythmia, survival
      of the animals is worse. However, such prevaccination improved survival of the
      animals due to reduction of reperfusion trauma in animals after hemorrhagic shock
      in spite of conduction disorders and myocardial ischemia.

PMID- 17002044
TI  - [Experimental studies of pathogenesis of chronic fluoride intoxication].
AB  - The article presents the results of studies of occupational fluorosis
      pathogenesis on experimental model of chronic fluoride intoxication (CFI). In
      early fluoride intoxication, fluoride and calcium in the body are in compensatory
      relations. Later, they are disturbed. High reaction ability of fluoride in CFI is
      associated with hypocalciemia which triggers parathyroid hyperactivity. This
      results in hyperproduction of PHH which is unrelated with development of
      secondary hyperparathyrosis. CFI is accompanied also with elevated calcitonin
      having a hypocalciemic and hypophosphatemic action. The experiments showed double
      content of collagen fragments of bone tissue in urine of animals with fluoride
      intoxication which reflects resorption of bone tissue. Serum osteocalcin rose
      three-fold as it was unable to include in the bone tissue. There was also
      activation of lipid peroxidation in subnormal activity of respiratory enzymes.

PMID- 17002045
TI  - [Efficacy of sorption therapy in patients with cicatricial esophageal stenosis].
AB  - We examined 110 patients treated conservatively for cicatricial esophageal
      stenosis including expansion on the string. The patients were divided into three
      groups: controls (n = 35), receiving adjuvant SUMS-1 (n = 38) and given adjuvant
      enterosgel (n = 37). According to electron microscopy, enterosorbents make
      esophageal mucosa denser by decreasing interstitial spaces as a result of
      microcirculatory improvement and reduction of edema. Enterosorbents elevate total
      protein and sugar in the blood.

PMID- 17002046
TI  - [Effects of melatonin and epitalone on antioxidant system of rats depends on
      light conditions].

PMID- 17002047
TI  - [Models of experimental atopic bronchial asthma].

PMID- 17002048
TI  - [Cellular technologies in therapy for chronic multidrug-resistant pulmonary
      tuberculosis].

PMID- 17002049
TI  - [The results of work and experience of the Central Research Institute of
      Tuberculosis, Russian Academy of Medical Sciences, in the pilot areas in
      controlling, detecting, and treating tuberculosis (a cohort analysis)].
AB  - In the Russian Federation, the WHO program was launched in 1994 and it covered
      the whole country by 2005. Detection and therapeutic efficiency are suboptimal.
      The proportion of pulmonary tuberculosis averages 34.5% (21.0-61.0%). In terms of
      cessation of bacterial isolation, therapeutic efficiency averages 61.4% with a
      scatter of 37.4-75.0%. Social support has a considerable impact on the efficiency
      of treatment.

PMID- 17002050
TI  - [Efficiency of a new standard chemotherapy regimen in the treatment of patients
      with recurrent pulmonary tuberculosis].
AB  - The efficiency of conventional chemotherapy regimens was comparatively studied in
      75 patients with recurrent pulmonary tuberculosis. In the patients with recurrent
      pulmonary tuberculosis, conventional chemotherapy regimen "2b" including
      isoniazid, rifampicin, pyrazinamide, ethambutol, fluoroquinolone (ofloxacin,
      ciprofloxacin, and levofloxacin), and canamycin (amikacin) versus conventional
      chemotherapy regimen "2a" including isoniazid, rifampicin, pyrazinamide,
      ethambutol, and streptomycin could cease bacterial isolation after 3-month
      therapy, as evidenced by sputum microscopy (86.1 and 62.5%, respectively; p <
      0.05). Cavity closure was more frequently observed after 6-month chemotherapy
      using regimen "2b" (76.7 and 48.0%, respectively; p < 0.05). In patients with
      recurrent pulmonary tuberculosis who isolated Mycobacterium tuberculosis (MBT)
      resistant to isoniazid and other antituberculous drugs (exclusive of rifampicin),
      3-month use of conventional regimen "2b" led to cessation of bacterial isolation
      (as evidenced by the inoculation test) in 66.7% of cases; but this did not occur
      with conventional regimen "2a" in any case. Similarly, 3-month use of regimens
      "2b" and "2a" in patients isolating MBT resistant to rifampicin and other agents
      (exclusive of isoniazid) resulted in the cessation of bacterial isolation in 80
      and 0% of cases, respectively. In multidrug resistance, these parameters were
      11.1 and 0%, respectively.

PMID- 17002051
TI  - [Differential diagnosis of tuberculosis of respiratory organs and pulmonary
      eosinophilia].
AB  - The reasons for misdiagnosis of tuberculosis in patients with pulmonary
      eosinophilia were analyzed, by using 6 clinical cases as an example. In most
      cases, the reasons for diagnostic errors are underestimation of elevated
      eosinophil levels and late afterexamination to verify the diagnosis. With general
      practitioners' increasing alertness, the inefficiency of antibiotics in patients
      with initially presumed pneumonia is frequently interpreted as an argument in
      favor of tuberculosis. Examining the cellular composition of bronchoalveolar
      lavage permits verification of the diagnosis of pulmonary eosinophilia in
      questionable cases. It is advisable to use a short course of test therapy with
      small-dose glucocorticosteroids for differential diagnosis of tuberculosis and
      pulmonary eosinophilias.

PMID- 17002052
TI  - [Efficiency of chemotherapy of destructive pulmonary tuberculosis, based on the
      results of rapid detection of drug sensitivity to isoniazid and rifampicin with
      the "TB-Biochip" test system].
AB  - To evaluate the efficiency of chemotherapy used in patients with pulmonary
      tuberculosis by the results of a rapid detection of drug resistance (DR) to
      isoniazid and rifampicin on a "TB-Biochip" test system versus the standard
      treatment with its subsequent correction by the data of determination of
      Mycobacterium tuberculosis (MBT) resistance by the absolute concentration
      technique (ACT), the study included 208 patients with pulmonary tuberculosis. The
      patients were divided into 2 groups: 1) those in whom MBT sensitivity to
      antituberculous agents was determined on a "TB-Biochip" test system to detect
      mutations in the MBT genes rpoB, katG, inhA, ahpC that were responsible for MBT
      sensitivity to rifampicin and isoniazid and by ACT; 2) those in whom this was
      determined by only ACT. The results of a test for MBT sensitivity to rifampicin
      and isoniazid were obtained within 2 days before chemotherapy in Group 1 and 2
      months after chemotherapy in Group 2. In Group 1, antituberculous chemotherapy
      was used, by taking into account MBT sensitivity to isoniazid, rifampicin, or
      their combination; in Group 2, the drugs were given by the standard regimens with
      their subsequent correction following 2 months by the results of ACT. The timely
      initiation of treatment with reserve drugs in the detection of drug sensitivity
      in MBT could achieve higher therapeutic efficiency and in a shorter space of
      time.

PMID- 17002053
TI  - [Artificial pneumoperitoneum in the complex treatment of pulmonary tuberculosis
      patients isolating drug-resistant mycobacterium tuberculosis].
AB  - The pretreated patients who isolated drug-resistant Mycobacterium tuberculosis
      (MBT) were randomly divided into 2 groups. A multidrug-resistant MBT strain was
      isolated from 77 and 62.2% of patients in the study and control groups,
      respectively. Artificial pneumoperitoneum (PP) was applied to the study group
      patients (n = 95) during adequate chemotherapy. In the control group (n = 43),
      only chemotherapy was performed in accordance with the data of a MBT drug
      sensitivity test. The results were assessed by the trend in bacterial isolation
      cessation and decay cavity closure. In the group of patients treated with PP and
      chemotherapy, sputum inoculation abacillarity occurred in 72.6 and 95.8% by
      months 4 and 6, respectively; in the control group, this did in 48.8 and 65.1% in
      the same periods. Moreover, decay cavity closure was noted in 95.1% in the study
      group and in 63.7% in the control group following 6 months of treatment.

PMID- 17002054
TI  - [Chemotherapy for tuberculosis in children and adolescents: problems and ways of
      their solution].
AB  - Treatment of 329 patients aged 4-17 years who had first detected tuberculosis was
      analyzed. The clinical pattern is mainly represented by infiltrative, focal
      tuberculosis and tuberculosis of intrathoracic lymph nodes (94.5%) and, in single
      cases, by other forms of tuberculosis. Treatment was performed according to
      regimens I and III. The time of abacillation is 1-2 months shorter than positive
      X-ray changes. In this connection, the results of X-ray monitoring may be
      regarded as the leading criterion for completion of intensive care.
      Microbiological monitoring methods should be primarily used to evaluate the
      initial combination of chemotherapy. The active application of pathogenetic
      treatment modalities that promote the acceleration of reparative processes
      (physiotherapy in particular) generated the necessity of using 3 antituberculous
      agents in the phase of treatment continuation.

PMID- 17002055
TI  - [Characteristics and causes of the torpid (lingering) course of intrathoracic
      tuberculosis in children, the specific features of chemotherapy and outcomes].
AB  - To study the causes of the torpid course of intrathoracic tuberculosis in
      children and to develop preventive measures and effective treatment options, the
      authors conducted clinical, X-ray, microbiological, immunological, and
      biochemical studies and treated 90 children with the torpid course of
      intrathoracic tuberculosis. The specific features of detection and the clinical,
      X-ray, and laboratory characteristics of a process were studied. A procedure of
      chemotherapy was devised, which could achieve recovery in 55.6% of the children
      with minimum residual changes being observed. Analysis of the specific features
      of the torpid course of intrathoracic tuberculosis has revealed the main causes
      of this course, which are imperfection of measures for its early detection among
      healthy and risk-group children, which results in the late diagnosis of the
      process and imperfection of preventive measures.

PMID- 17002056
TI  - [Individual approaches to complex treatment of disseminated tuberculous processes
      in adolescents].
AB  - Complex treatment including an individual selection of chemotherapy regimens with
      their timely correction and various laser therapy modalities was used in 147
      adolescents with a first detected disseminated pulmonary tuberculous process
      (DPTP). All the patients were initially given treatment regimen 1. According to
      the results of chemotherapy correction (adverse reactions to antituberculous
      agents and drug resistance of Mycobacterium tuberculosis), the patients were
      divided into 3 groups. Inclusion of reserve-series drugs into the initial
      combination for most critically ill patients could prevent an exacerbation of
      tuberculosis in most cases (89.7%) during therapy. The employment of various
      laser therapy modalities in combination with an individual approach to using
      drugs in the intensive phase of treatment enhanced its efficiency in patients
      with DPTP, by accelerating the periods of positive changes by 1.5-2 months. This
      made it possible to achieve a smooth course of tuberculosis in 92.5% of patients
      with high rates of bacterial isolation cessation (99.2%) and decay cavity closure
      (97.6%).

PMID- 17002057
TI  - [Outcomes of video-assisted thoracic lung resections and pneumonectomies in
      patients with pulmonary tuberculosis].
AB  - The paper pools some experience with 6 videothoracoscopic and 505 video-assisted
      thoracoscopic (VATS) resections of the lung and 105 VATS pneumonectomies. The
      bulk of the operations [451 (73.2%)] was made for pulmonary tuberculosis in
      patients aged 7 to 77 years. 81% operations by separately treating root elements,
      including all pneumonectomies and major lung resections, were performed. A new
      SOMI-80 suturing apparatus designed for mini-invasive surgery was employed to
      suture lung tissue in most cases. Intraoperative and postoperative complications
      occurred in 5 and 8 cases, respectively. The efficiency of operations for
      tuberculosis was 98.6%.

PMID- 17002058
TI  - [Clarythromycin in the treatment of exacerbations of chronic obstructive lung
      disease].
AB  - Clarythromycin (Clerimed) is an antibiotic that has a high antibacterial
      potential, is successfully used in the treatment of moderate and severe
      exacerbations of Stage II chronic obstructive lung disease (COLD). Comparison of
      the clinical efficacy of Clerimed with beta-lactams and respiratory
      fluoroquinolones has indicated the equal clinical efficacy of the compared groups
      of drugs. A functional and laboratory monitoring of patients with an exacerbation
      of COLD treated with Clerimed has established that the most pronounced changes
      (improvement) occur within the first week of antibiotic therapy, which is typical
      of control patients. The side effects of Clerimed have been found to occur not
      more frequently than those of other antibiotics and they are considered to be
      slight. Clarythromycin may be recommended for the starting therapy of
      exacerbations of COLD in everyday practice.

PMID- 17002059
TI  - [Disease of respiratory organs in millers].

PMID- 17002060
TI  - [Qualitative assessment of metabolic shifts accompanying the acutely progressive
      course of pulmonary tuberculosis].
AB  - Eighty-one patients with acutely progressive pulmonary tuberculosis (APPT) (a
      study group) and 63 patients with involutive pulmonary tuberculosis (a control
      group) were examined. The magnitude of a systemic inflammatory response was
      estimated by the values of acute phase reagents (APR) and the blood protein
      spectrum; the body's iron provision, the state of the hemostatic and fibrinolytic
      systems, the functional status of mononuclear leukocytes and neutrophils were
      determined by the basal level of oxygen-dependent and nitrite oxide metabolism
      and by the capacity of these systems to respond to specific stimulation. In APPT,
      along with increased APR levels reflecting the mobilization of various components
      of endogenous defense, the serum (plasma) was found to show the signs of
      metabolic decompensation as increased catabolic processes and hepatic protein
      synthesizing dysfunction in the presence of intravascular inactivation of
      functionally significant proteins. Noteworthy is hypochromic anemia caused by the
      body's redistribution of iron (in the absence of its genuine deficiency) and by
      the reduced plasma concentration of transferring. The patients with APPT had a
      significant hypercoagulation syndrome with the signs of latent intravascular
      blood coagulation. Antimicrobial defensive processes involved mononuclear
      leukocytes and neutrophils wherein free radical oxidation and nitric oxide
      generation became intensive. In APPT, the permanent reirritation of these systems
      led to the exhaustion of functional reserves of cells and their response to
      specific stimulation diminished. In the neutrophils, rearrangement of their
      metabolism correlated with other manifestations of a systemic inflammatory
      response and in the mononuclear leukocytes, this correlated with the size of a
      bacterial population and with the presence of drug sensitivity/resistance of the
      causative agent.

PMID- 17002061
TI  - [In vitro development of rifampicin resistance in the epithelial cells].
AB  - It has been first in vitro demonstrated on a model of epithelial cells that
      rifampicin may develop not only at the level of Mycobacterium tuberculosis, but
      also at the level of somatic cells. The mechanism of this phenomenon, its
      specificity (whether cross resistance to other antituberculous agents will
      occur), the way it puts into effect under the conditions of a microorganism, and
      how promptly it may be gone after discontinuation of the drug remain unknown. The
      effect of rifampicin on the functional activity of Pgp is an important factor
      that influences as a result not only the absorbability of drugs, but also normal
      transport processes in the body. These aspects seem to be topical and are the
      subject for further studies. The authors have obtained an epithelial cell line
      that resides in the presence of 100 microg/ml of rifampicin and that is 2-2.5
      times more resistant to the drug as compared with the parental line. The cells of
      this line are 2-2.5 times more active in discharging the substrate rhodamine-123
      for P-glycoprotein than those of the parental line, which suggests the enhanced
      functional activity of P-glycoprotein. The presence of P-glycoprotein in this
      line is confirmed by the action of this protein-specific blocker verapamil. At
      the same time rifampicin is not a substract for P-glycoprotein. Therefore, the
      mechanism of rifampicin resistance is unassociated with the functional activity
      of P-glycoprotein. The mechanism of the resistance remains open. At the same
      concentration (100 microg/ml), rifampicin can block the functional activity of P
      glycoprotein. These results suggest the double mechanism of rifampicin in its
      long presence in the culture medium: as an inductor and a blocker of P
      glycoprotein functional activity. The findings point to the fact that the
      pharmacokinetics of rifampicin and co-administered dtugs may change during their
      long use.

PMID- 17002062
TI  - [Evaluation of the efficiency of activity of the liposomal form of isoniazid
      against different types of mycobacteria in vitro].
AB  - M. avium and three M. tuberculosis strains were used as an example to study the
      bacteriostatic activity of the liposomal form of isoniazid in the liquid nutrient
      medium by serial dilutions. Unlike isoniazid in solution, its liposomal form was
      found to suppress the multi plication of all study mycobacterial samples and
      diminishes their viability, but at different concentrations. The liposomes that
      did not contain the drug exerted an inhibitory effect only on the M. tuberculosis
      strains H37Rv and Erdman. It is suggested that the change in isoniazid
      sensitivity results from the effect of liposomal phospholipids on some
      mycobacterial enzymes. Electron microscopy indicated that the liposomal form of
      isoniazid is able to penetrate into the alveolar macrophageal cytoplasm of guinea
      pigs just 30 min after incubation.

PMID- 17002064
TI  - [Paradoxical upgrading reaction in a patient with lymph node tuberculosis].

PMID- 17002063
TI  - [Infections caused by multiresistant bacteria].
AB  - Bacterial resistance to antibiotics is enhanced by antimicrobial selection
      pressure by antibiotics and the crossed transmission. Multiresistant bacteria
      (MRB) are involved in 1/5 of nosocomial infections and the 3/4 of the MRB are
      meticillin resistant Staphylococcus aureus and extended-spectrum-beta-lactamase
      producing Enterobacteriaceae. The epidemic diffusion of these strains is still
      poorly controlled in our hospitals. The fight against the diffusion of these
      bacteria requires not only to screen patients harbouring antibiotic-resistant
      bacteria and respect hygiene measures, but also actions aiming at reducing the
      weight of selection pressure by antibiotics.

PMID- 17002065
TI  - [Treating ischemic stroke as an emergency to prevent cerebral infarction or limit
      its spread].

PMID- 17002066
TI  - [Transient ischemic stroke].
AB  - According to the new definition proposed by the TIA working group, transient
      ischemic stroke (TIA) is "a brief episode of neurologic dysfunction caused by
      focal brain or retinal ischemia, with clinical symptoms typically lasting less
      than one hour, and without evidence of acute infarction." Patient presenting with
      a TIA should be investigated and treated urgently because the risk of ischemic
      stroke is about 10% at one month with 50% of these events occurring during the
      first 48 hours. Atherosclerosis, cardioembolism and small vessel disease account
      for the majority of TA. Aspirin should be started as soon as possible after brain
      imaging has been performed. Other treatment such as oral anticoagulants or
      carotide surgery may be necessary, depending on the result of the electronical
      work up.

PMID- 17002067
TI  - [Acute ischemic stroke: time is brain!].
AB  - Care of patients with acute ischemic stroke in dedicated stroke units reduces the
      rates of death and disability independently from any specific treatment. The only
      validated treatment for acute ischemic stroke is thrombolysis with intravenous
      alteplase. Its efficacy is strongly time-dependent. It is currently demonstrated
      for an administration up to 3 hours after symptom onset. Intravenous fibrinolysis
      for acute ischemic stroke is associated with an increased risk of symptomatic
      intracerebral haemorrhage. This can be reduced by rigorous application of
      recommendations for drug prescription. The efficacy of intravenous alteplase is
      relatively weak in patients with large artery occlusion. Combined therapies,
      using transcranial ultrasound, intraarterial thrombolysis, or clot retrieval
      devices are being evaluated to improve the efficacy of thrombolysis.

PMID- 17002068
TI  - [Brain imaging patterns after stroke].
AB  - The advent of new imaging techniques, such as diffusion-weighted sequences, has a
      great impact on the diagnostic imaging in stroke. The aim of the present paper is
      to review the brain imaging patterns after stroke, highlight the usefulness of
      imaging technique for the diagnosis and etiological work-up after stroke. Three
      causes of ischemic stroke (cerebral venous thrombosis, aortic arch atheroma,
      patent foramen ovale) are detailed.

PMID- 17002069
TI  - [Prevention of vascular events after transient ischemic attack or cerebral
      infarct].
AB  - After a first cerebral ischemic event, secondary prevention should be started as
      soon as possible, especially in transient ischemic attacks where the risk of
      recurrence is the highest, especially during the first week, needing a diagnostic
      workup in a short period of time, secondary prevention measures depending on the
      presumed cause of the event. Secondary prevention of vascular events after
      transient ischemic attack or cerebral infarct consists of 3 types of strategies:
      1. treatment of risk factors for stroke, especially high blood pressure, high
      cholesterol and smoking cessation; 2. aspirin (50 to 325 mg), or clopidogrel, or
      association aspirine-dipyridamole in high-risk subjects, or warfarin in patients
      with high-risk cardiopathies; and 3. carotid surgery in patients selected by
      clinical and imaging criteria. Other strategies are currently partly under
      evaluation: statins in normocholesterolemic ischemic stroke patients without
      coronary event, angioplasty with stenting. Audits of practice are necessary to
      determine whether patients are actually treated according to scientific evidence.
      This is a crucial issue if we want the results of trials to be translated in the
      true life, and really improve health at the community level.

PMID- 17002070
TI  - [Daily life activities following cerebrovascular infarct].
AB  - Cerebro-vascular disease is the first cause of handicap in France. Disabilities
      in daily life activities are due to motor, visual and cognitive impairments
      following a stroke. Difficulties arise while grooming, getting dressed, eating,
      moving around ... the WHO presents with a new classification of functioning, that
      has been followed by a recent law in France. The aim is to place the handicapped
      citizen in daily life and not just to list his/her deficiencies. Rehabilitation
      after stroke has to establish functional objectives early so as to include daily
      life goals in re-education.

PMID- 17002071
TI  - [Stroke centers and stroke networks].
AB  - Admission to a stroke unit represents an established and efficient treatment for
      acute stroke. However, stroke care is yet not enough developed in many countries.
      In France, the organisational model is based on stroke unit admission for acute
      stroke patients associated with a network of stroke units covering the majority
      of the territory. That model fulfils the commitment of equity of access to
      medical care for the whole population, and optimises use of resources. The task
      of the five-year organisational plan Schema regional d'organisation sanitaire is
      aimed achieve that goal.

PMID- 17002072
TI  - [Patient's medical record. Cerebrovascular accident or cerebral infarction].

PMID- 17002073
TI  - [Entrance in medical school (1)].

PMID- 17002074
TI  - [Adrenal insufficiency].

PMID- 17002075
TI  - [Acute hepatitis. Biological hepatic anomalies in asymptomatic persons].

PMID- 17002076
TI  - [Chronical venous insufficiency. Varicose veins].

PMID- 17002077
TI  - [Bronchopulmonary infections in the infants, child and adult].

PMID- 17002078
TI  - [The museum Dr Guislain of Gent. History of psychiatry].

PMID- 17002079
TI  - What ever happened to faculty governance?

PMID- 17002080
TI  - Instruction in mastery goal orientation: developing problem solving and
      persistence for clinical settings.
AB  - Individuals with a mastery orientation are more motivated to persist and increase
      their competence. Although studies have demonstrated the usefulness of explicitly
      teaching mastery goal orientation, no interventions have been used in nursing
      education. The purpose of this study was to determine whether mastery goal
      orientation could be rapidly acquired by nursing students via a short-term
      educational intervention. Nursing students from five programs participated in a 3
      week intervention. Participants were matched by demographic profile and pretest
      goal orientation scores before being randomly assigned to experimental and
      control groups. Goal orientation was measured before and after the intervention.
      Students in the experimental group increased their mastery orientation
      significantly, while reducing their performance orientation somewhat. They
      persisted to solve problems, while students in the control group gave up more
      easily when faced with a difficult task. Early development of mastery goal
      orientation that promotes problem solving and persistence for clinical settings
      can be a powerful adjunct to undergraduate nursing education.

PMID- 17002081
TI  - When will faculty retire?: Factors influencing retirement decisions of nurse
      educators.
AB  - This cross-sectional study surveyed a random sample of 129 nurse educators
      teaching in 61 U.S. schools of nursing. After the educators indicated their
      desire to participate, the survey instrument was e-mailed to them for completion;
      a 37.6% response rate was obtained. Demographically, the typical respondent was a
      healthy, 52-year-old, Caucasian female with a PhD in nursing. Outcomes reflected
      that respondents' mean anticipated age of retirement was 64.4; however, the
      optimal age of retirement desired by respondents was younger (62.4). The most
      influential factor affecting the timing of retirement was financial status.
      Workplace issues, personal and family health, and attitudes about retirement were
      other factors that affected participants' retirement decisions. The study
      findings indicate that nurse educators, as a group, do not plan to work beyond
      age 65.

PMID- 17002082
TI  - Evaluation of concept mapping in an associate degree nursing program.
AB  - The purpose of this project was to evaluate concept mapping as a clinical
      teaching-learning activity that reflects critical thinking by promoting
      identification of nonlinear relationships among the components of the nursing
      process. The sample involved 28 associate degree nursing students from one
      graduating class. Students completed one map each in the second and fourth
      semesters and two maps in the fifth semester, for a total of four concept maps.
      The students' learning activity was to create a concept map on a blank sheet of
      paper describing the clients' physiological and psychosocial needs and nursing
      care and the relationships among concepts. As students progressed through the
      curriculum, there was a steady increase in the mean scores and the average number
      of cross-links in their concept maps. Cross-links indicated students' ability to
      use nonlinear thinking to identify relationships among concepts. The results of
      this study support the use of concept maps as an effective teaching-learning
      activity and support concept mapping as an evidence-based nursing education
      strategy.

PMID- 17002083
TI  - Spiritual development of nursing students: developing competence to provide
      spiritual care to patients at the end of life.
AB  - Nurses spend more time with their patients than do other health care workers.
      Therefore, the spiritual needs of patients must be recognized as a domain of
      nursing care. Holism cannot exist without consideration of the spiritual aspects
      that create individuality and give meaning to people's lives. The purpose of this
      article is to provide nursing faculty with tools that may be used to develop
      spiritually knowledgeable nursing students who can overcome barriers to providing
      spiritual care to end-of-life patients. Our students were required to complete
      care maps to ensure they are prepared for patient care at the end of life. In
      this article, we present tools that faculty and students may use to complete the
      spiritual concept in care mapping. The literature on spirituality is reviewed,
      use of care mapping in nursing curricula is described, and our teaching approach
      to develop nursing students who are skilled at providing spiritual care is
      explained. Three case studies and care maps created by former students are also
      presented to demonstrate examples of spiritual competence.

PMID- 17002084
TI  - Generational (age) differences in nursing students' preferences for teaching
      methods.
AB  - A generational age transformation is occurring in nursing classrooms across the
      United States. Nurse educators need to prepare for the different values and
      expectations of students from Generation X and the newly emerging Generation Y in
      the educational environment. This quantitative, descriptive research begins to
      examine the preferences and expectations of these generations regarding teaching
      methods.

PMID- 17002085
TI  - Nursing students' and faculty members' knowledge of, experience with, and
      attitudes toward complementary and alternative therapies.
AB  - This study was designed to describe and compare the knowledge, experience, and
      attitudes of nursing faculty and students (undergraduate and graduate) regarding
      complementary and alternative therapies (CAT). A cross-sectional survey (N = 153)
      of undergraduate (n = 41) and graduate (n = 57) students and faculty (n = 55) was
      conducted in one school of nursing. Most participants were White (87%) and female
      (78%). More than 70% of the students and faculty agreed that clinical care should
      integrate the use of CAT. More than 85% desired more education about CAT,
      especially in undergraduate nursing curricula. More than 65% agreed that the
      clinical nurse specialist or nurse practitioner role should include the use of
      CAT in their practice, and more than 50% agreed that they had some knowledge of
      CAT, but only approximately 30% had some experience with CAT. Faculty and
      students expressed positive attitudes toward integrating CAT into the
      undergraduate nursing curriculum and nursing practice. Faculty development and
      nursing research are needed to facilitate curriculum change and integrate CAT
      into nursing programs at all levels.

PMID- 17002086
TI  - Linking competency-based assessment to successful clinical practice.
AB  - Competence is essential for health care professionals; graduates must meet the
      responsibilities associated with a particular position. At one community college,
      nursing faculty have used a competency-based approach to educate and evaluate
      associate degree nursing students. The nursing curriculum is designed to allow
      for the inclusion of laboratory experiences for each nursing course and requires
      students to complete a clinical performance examination before advancing to the
      next level. The examination is designed as a clinical scenario with three to four
      responsibilities completed in random order. Critical elements developed by
      faculty are used to assess student competence. The increase in graduates'
      abilities to complete these skills has been valuable to both employers and
      graduates. Since 1992, with the implementation of a competency-based curriculum,
      the program's NCLEX-RN pass rates (98%) have been consistently above the national
      and state averages.

PMID- 17002087
TI  - [Study on second filtering algorithm based on tracing the interfering spectral
      peaks of radar non-contact life-parameter detection system].
AB  - To develop a filtering algorithm which could trace the spectral peaks of the
      interference and which was used to extract the breath signal with the same band
      interference in radar non-contact life-detecting system, second filtering
      algorithm was studied. Through first filtering,the probable interfering spectral
      peaks (ISP) could be detected by Yule-Walker spectrum estimating and could be
      located by calculating the coefficients of normalized cross-correlation function
      according to standard breath signal. Thus the breath signal could be extracted
      through a second filtering. By using the second filtering algorithm (SFA), the
      same band interfering spectral peaks with breath signal could be recognized and
      inhibited. So we conclude that the same band mono-ISP could be inhibited by using
      SFA and breath signals could be effectively extracted.

PMID- 17002088
TI  - [Automatic segmentation of three dimension medical image series].
AB  - We propose an improved version of regional competition algorithm in this paper,
      and apply it to the automatic segmentation of medical image series, particularly
      in the segmentation and recognition of brain tumor. The traditional regional
      competition is enhanced by combining the attractive aspects of fuzzy
      segmentation, and thus it provides an efficient approach to segment the fuzzy and
      heterogeneous medical images. In order to perform regional competition on medical
      image series, we utilize the segmentation result of a slice to initiate the next
      segmented slice, while the first slice is initialized using regional growing
      algorithm. Moreover, we develop an algorithm to recognize the tumors
      automatically, taking into account its characters. Experimental results show that
      our algorithm performs well on the segmentation of magnetic resonance imaging
      (MRI) image series with high speed and precision.

PMID- 17002089
TI  - [Study on double feedback current source for biologic impedance measurement].
AB  - A double feedback current source for biologic impedance measurement is designed
      in order to solve the problem on the poor constant-current characteristic under
      higher frequency and meet the request for the ability to eliminate the direct
      current signal. The voltage controlled current source based on the second
      generation current conveyor theory is presented, which has good output impedance
      and anti-direct current characteristics by using the direct current feedback unit
      and input buffer. The closed loop control of current amplitude is implemented by
      means of the direct digital synthesizer and multiplication demodulation
      technique, which improves the constant-current characteristic of the current
      source.

PMID- 17002090
TI  - [Experimental studies of carcino-embryonic antigen immunosensor based on
      piezoelectric resonate technology of quartz crystal].
AB  - In order to construct a new type of piezoelectric quartz immunosensor for the
      determination of carcino-embryonic antigen (CEA), the sensor detection pools were
      consisted of plastic loops and crystals that were 10 MHz quartz AT-cut with gold
      coated electrodes and the immobilization of the monoclonal antibody against CEA
      onto gold electrode surface of the quartz crystal was accomplished via Thiol
      method. Then the immunosensors were used in clinical laboratory. The experimental
      results showed that the piezoelectric immunosensor had good response to CEA, the
      frequency shifts were linearly dependent on CEA concentration in the range of
      1.56 to approximately 50.00 ng/ml, other antigens such as alpha fetoprotein
      (AFP), prostate specific antigen (PSA), human chorionic gonadotropin (hCG) did
      not interfere with the sensor's response. The results obtained from this method
      were in satisfactory accordance with those obtained by radio immunoassay(P>0.05),
      The correlation coefficient was 0.90. Piezoelectric immunosensor for
      determination of CEA has the advantage of high sensitivity, high specificity,
      unnecessary labeling, simple performing, rapid analysis, low cost, real-time
      detection and repeated use, etc. It can be used for detecting serum CEA in
      clinical laboratory.

PMID- 17002092
TI  - [An algorithm based on deformable contour models for medical image segmentation].
AB  - This paper provides a new medical image segmentation algorithm using a deformable
      contour model, which integrates Fuzzy C-Means(FCM) Clustering technique and
      deformable contour model. An external fuzzy constrain is defined from the
      membership function value of FCM, which joins the external constrain of the
      deformable model and drives the deformable model towards the contour ideal edge
      of the object. Examples are presented to demonstrate the efficiency and
      feasibility of the approach on spinal MRI images and the results are encouraging.

PMID- 17002091
TI  - [The development of database system of electrocardiographic information].
AB  - An ECG information database system was established with 1297 ECG information
      records and clinical informations. The data and the analysis software in this
      database can be shared with the international physiological signal databases such
      as MIT-BIH Arrhythmia. The establishment of this database will facilitate the
      clinical interpretation, diagnosis and prediction of cardiovascular diseases,
      especially the cardiac sudden death (SCD).

PMID- 17002093
TI  - [A new approach to wavelet-based P-wave detection].
AB  - According to the characteristics of four basic P morphologies, combining the
      wavelet transform and the amplitude and slope of transformed P wave, a new P-wave
      detecting method based on "wavelet-amplitude-slope" algorithm is presented: First
      search out all modulus maximum pairs to satisfy the threshold after wavelet
      transform, and then applying the amplitude and slope criterion exclude the
      interferes and detect the P peak and its shape, last determine the onset and end
      of P wave respectively which should be separately calculated for single-peak and
      double-peak P wave (or biphasic P wave). The approach is applied in experiments
      of data from MIT/BIH database and randomly collected data of clinical ECG. The
      experimental statistical results shows that the correct detecting rate is as high
      as 96% compared to manual annotation.

PMID- 17002094
TI  - [Computer-aided diagnosis of fatty liver based on ultrasonic images].
AB  - This study aims to provide a computer-aided method for the diagnosis of fatty
      liver by B-scan ultrasonic imaging. Fatty liver is referred to the infiltration
      of triglycerides and other fats of the liver cells, which affected the texture of
      liver tissue. In this paper, some features including mean intensity ratio, as
      well as angular second moment, entropy and inverse differential moment of gray
      level co-occurrence matrix were extracted from B-scan ultrasonic liver images.
      Feature vectors which indicated two classes of images were created with the four
      features. Then we used kappa-means clustering algorithm, self-organized feature
      mapping (SOFM) artificial neural network and back-propagation (BP) artificial
      neural network to classify these vectors. The accuracy rate of kappa-means
      clustering algorithm was 100% for normal liver and 63.6% for fatty liver. The
      results of SOFM neural network showed that the accuracy rate was 84.8% for normal
      liver and 90.9% for fatty liver. The accuracy rate of neural network was 100%
      both for normal liver and fatty liver. This technology could detect the
      characteristics of B-scan images of normal liver and fatty liver more accurately.
      It could greatly improve the accuracy of the diagnosis of fatty liver.

PMID- 17002095
TI  - [Promoter recognition using genetic algorithms and neural network].
AB  - A new model is developed to recognize eukaryotic promoter sequences from non
      promoter sequences based on genetic algorithms and neural network in this paper.
      Experiment results demonstrate the effectiveness of the system to recognize the
      promoter sequences on the training set and on the test set. The mean recognition
      rate is as high as 99% on the training set and 97% on the test set, which shows
      the algorithms has great prospect application in promoter recognition.

PMID- 17002096
TI  - [A new method for visual SARS DNA sequences analysis].
AB  - Traditional DNA sequence analysis is based on sequence alignment, while a new DNA
      visual sequence analysis is proposed in this paper. Based on S. Wolfram's
      cellular automation theory, the method transfers one-dimensional DNA sequence
      into two-demensional visual image. Applying this method to SARS DNA sequence
      analysis, a characteristic of SARS-CoV differing from non-SARS is discovered.
      Compared with all known coronaviruses' images, It is found that this is a unique
      characteristic of SARS virus, and it is helpful to clinical identification of
      SARS.

PMID- 17002097
TI  - [Antigen-antibody reaction model of solid-phase surface and active biochip
      system].
AB  - To overcome the present limitations of passive biochip, based on the basic
      principle of antigen-antibody reaction, we develop an antigen-antibody reaction
      model of solid-phase surface and design a novel active biochip system according
      to this model, which introduces the negative pressure and controlling devices to
      control the immunoreactions on the nitrocellulose (NC) membrane. From the
      computer simulation results, this is a rapid, stable, robust and practicable
      system, which can be used to increase the efficiency of immunoreactions and
      improve the reproducibility and accuracy of biochip analysis.

PMID- 17002098
TI  - [Study of biomechanical effects on the reconstruction of mandible defect with
      autogenous bone grafts].
AB  - The biomechanical effects of the reconstructed mandible with autogenous bone
      grafts were analyzed and evaluated, under simulated mechanical environment of
      occlusion. Based on anatomical feature of the human skeleton, muscle system and
      the clinical B, BS"S" and RB"S"defect patterns, the modularized model of mandible
      and the three finite element models of the fibula grafts and iliac crest grafts
      reconstruction mandible were made. The stress state calculations under bite force
      were also processed. The findings are as follows: Along the right connection area
      to left connection area (corresponding to far-end of the molar teeth alveolar
      ridge and the chin section respectively), the stress state on the various grafted
      bone all changes from compression stress to tensile stress. There is obvious
      change on the stress distribution between the fibula type reconstruction mandible
      and normal one. The stress on the grafted bone which is mainly made up of
      cortical bone is approximately 5 times higher than that of normal, which
      indicates the obvious stress shielding effect; the stress distribution of the
      iliac crest type reconstruction mandible is close to the normal mandible, the
      iliac crest used is mainly made up of cancellous. Therefore, the mechanical
      properties of the reconstructed mandible with iliac crest are more similar to
      normal mandible, which is beneficial to wound healing and further functional
      reconstruction.

PMID- 17002099
TI  - [Numerical study on inspiratory flows in two and three generation bronchi of
      human lung airways].
AB  - The main physiological function of respiratory system is exchange of oxygen and
      carbon dioxide between atmosphere and blood. Its physiological process is closely
      related with air flow and transport in respiratory airway. This paper studies
      numerically the inspiratory flows in a two generation and a three generation
      bronchial airway. The numerical results of the two generation bronchi show that
      the present computations fit the available experiments very well. For three
      generation bronchi, no separation appears within the whole airway under normal
      breathing rate, which is contrary to the occurrence of separation at even low
      Reynolds number by the previous two dimensional models. Strong secondary flow
      phenomenon, skew and m-shaped main flow velocity profiles are found in the
      airways due to geometrical curvature and bifurcation. These increase shear stress
      acting on the inner wall as well as on the anterior and posterior wall in the
      bifurcating airways. In the end bronchi of the three generation airway, the mass
      flow rates in medial and lateral bronchi are unequal, and the mass flow ratio
      between the medial and the lateral bronchi is 1.2 at the flow conditions
      considered.

PMID- 17002100
TI  - [Change of zero-stress state of portal vein in the rat during the pathogenesis of
      intrahepatic portal hypertension].
AB  - A model of intrahepatic portal hypertension was established in SD rats by
      injection of carbon tetrachloride (CCl4). By observing the opening angle of the
      portal vein, the zero-stress state of the portal veins was studied at different
      time during the pathogenesis of intrahepatic portal hypertension. After CCl4
      injection, the opening angles of the portal veins were increased, in the tenth
      week, they were much greater than those in the corresponding controls (P<0.05).
      The results suggest that during the pathogenesis of portal hypertension, unequal
      remodeling exists in the portal veins to change its biomechanical properties, and
      the residual stress and strain of the portal veins in portal hypertensive rats
      are greater than those in normal controls.

PMID- 17002101
TI  - [Posterior glass fiber-reinforced composite resin-bonded fixed partial dentures:
      A 3-dimensional modeling and finite element numerical analysis].
AB  - The method of modeling and mesh generation about 3-unit tooth/restoration complex
      were established. The three-dimensional finite element models were subjected to
      four types of occlusal load applied to pontic element to evaluate 3 fiber
      framework designs and 3 cavities preparation configurations. By comparing the
      difference of stress distribution, following conclusions were obtained: the
      principal stress under buccal-lingual cusp load in traditional fiber framework
      pontic increased by 6.22% compared to that in pure composite resin pontic;
      optimized fiber framework obviously reduced stress level under any load; modified
      cavities exhibited better stress transfer and decreased share stress at adhesive
      interface than traditional cavities.

PMID- 17002103
TI  - [Study on the performances of the positive pressure powered air-filter protective
      hood].
AB  - The positive pressure powered air-filter protective hood can prevent physicians
      and nurses from being infected by serious respiratory infections. The
      contaminated air is filtered by the high efficiency specific air-filter (HESA)
      and then transported into the hood by a blower to form about 140 +/- 10 Pa
      positive pressure environment, which makes the air in hood overflow out from the
      lower part of the hood, by which carbon dioxide and vapor can be removed, and
      excreted. The HESA's filters of simulative virus up to 99.9999% with the
      structure of double layers filtering. With going at 4 km/h pace on a walking
      vehicle wearing the hood, the testees' heart rate is 90-105/min oxygen saturation
      of the blood(SPO2) is 97%-98%. When the air flow is from 75 L/min to 125 L/min,
      this can meet the testees' physiological demand under heavy workload. Clinical
      trial results show that the hood can effectively protect the physicians and
      nurses from infection.

PMID- 17002102
TI  - [Effects of extracts from different parts of Folium perillae (L.) Britt. on
      Hemorrheological parameters in rats].
AB  - In order to provide experimental data for the development and application of drug
      in clinic, we determined the effects of extracts from different parts of folium
      perillae (L. ) Britt. on hemorheological parameters, extracted from leaves
      (folium perillae), seeds (fructus perillae) and peduncles (caulis perillae). The
      results showed that all extracts from different parts of folium perillae (L. )
      Britt. can significantly reduce the whole blood viscosity at low shear rate (10
      s(-1)), erythrocyte aggregation index, erythrocyte electrophoresis index
      (P<0.05), and the whole blood reductive viscosity at low shear rate (10 s(-1))
      (P<0.01). Extracts from folium perillae and caulis perillae can significantly
      decrease erythrocyte deformation index (P<0.05), whereas extracts from fructus
      perillae can not. Extracts from fructus perillae and caulis perillae can
      significantly decrease plasma viscosity at low shear rate(10 s(-1)), but extracts
      of folium perillae can not. Aspirin can only decrease the whole blood reductive
      viscosity at low shear rate and plasma viscosity (P<0.05). All extracts from
      different parts of folium perillae (L. ) Britt. had no significant effects on
      hematocrit, erythrocyte rigidity index, fibrinogen concentration , the whole
      blood viscosity and the whole blood reductive viscosity at middle and high shear
      rate (60 s(-1),120 s(-1)).

PMID- 17002104
TI  - [Study on the method of measurement of respiratory mechanical parameters].
AB  - Respiratory mechanical parameters are the key indexes in evaluating the
      respiratory function of an anaesthetized patient during operation. The
      measurement of respiratory parameters plays an important role in clinic, and can
      dynamically monitor the working state of a respirator, direct the use of a
      respirator and monitor the respiratory function of a patient in intensive care
      unit(ICU). This paper introduces a new method that will break the traditional
      limitations, can measure eleven respiratory parameters and demonstrate the
      results by digital and diagrams.

PMID- 17002105
TI  - [Experimental study of recovery force of surface-modified TiNi memory alloy rod].
AB  - The recovery force of Ti-Nb coated and uncoated TiNi shape memory alloy rods was
      investigated. The rods were 6.0 mm, 6.5 mm and 7.0 mm in diameter respectively.
      The mean transition temperature was 33.0 degrees C. The rods were stored at -18
      degrees C and pre-bent with a three-point bending fixture, the span was 20. 0
      centimeters and the deflections were 5.0 mm, 10.0 mm, 15.0 mm and 20.0 mm,
      respectively. The rods were then heated in a constant temperature saline solution
      chamber. The experimental temperature was 37.0 C and 50.0 C respectively. The
      recovery force was measured in a constant displacement mode on biomaterial test
      machine. The results showed that the recovery force of the memory alloy rod
      increased with increasing recovery temperature, rod diameter and deformation of
      both Ti-Nb coated and uncoated surface. The recovery force of Ti-Nb coated rods
      of 6.0 and 6.5 millimeter in diameter was lower than the uncoated rods in the
      same diameter. However, the recovery force of 7.0-mm-diameter rods showed no
      significant difference between coated and uncoated surface.

PMID- 17002106
TI  - [Hemodynamics study of cardiovascular system in vitro simulation].
AB  - In order to study the cardiovascular hemodynamic characteristics and evaluate the
      blood pump, we made a series of cardiovascular simulation devices which could
      reflect the hemodynamics of blood circulation system by the elastic chamber
      model, and tested the relations between cardiovascular hemodynamic parameters
      (such as systole pressure, diastole pressure, average pressure, pulsative
      pressure, flow rate) and ventricular afterload (peripheral resistance and
      vascular compliance) as well as cardiac output, diastolic period, systole period
      and preload. The effect of the parameters on the arterial pressure and flow rate
      was estimated when any one of the parameters was changed. The result of
      simulating experiment was coincided with that deduced from mathematical model and
      physiologic condition. Therefore the series of cardiovascular simulation devices
      can reflect the hemodynamics of blood circulation.

PMID- 17002107
TI  - [Study on fabrication of controllable microchannel structure scaffolds and
      rotating dynamic culture].
AB  - It is the critical technology for bone tissue engineering to fabricate scaffolds,
      especially to fabricate the internal microchannel of scaffolds. Utilizing
      stereolithography rapid prototyping indirect fabrication approach, suitable size
      microchannel structure scaffolds with orientation, branching, and
      interconnectivity under control was manufactured. Observation under light
      microscope showed that the arrange of microchannel size was 200-600 microm, the
      orientation and branching were accorded with designed structure, and all the
      microchannels were completely interconnected. Scaffolds seeded with osteoblast
      cells were put into 6-well plate and rotating 3D dynamic culture system which was
      developed in our lab. The morphology of osteoblasts and the development on the
      surface and internal microchannel of scaffolds were observed under scanning
      electron microscope (SEM). The results indicated that the dynamic culture
      permited an even distribution of cells across the surface of scaffolds, besides,
      a few cells grew into the lumen of microchannels.

PMID- 17002108
TI  - [Synthesis and characterizations of poly (ethylene glycol)-block-poly
      (glutamate)].
AB  - Amine-terminated poly (ethylene glycol) (PEG) was prepared by two steps. Firstly,
      potassium naphthalene was added to a solution of methoxypolyethylene glycol 5,000
      in benzene until the solution maintains green in half of an hour, then excess
      tosylchloride was introduced; secondly, the conversion of the tosylate into an
      amine was carried out by Gabriel synthesis. The block copolymer poly (ethylene
      glycol)-co-poly (gamma-benzyl L-glutamate ) could be obtained by ring-opening
      polymerization of gamma-benzyl-L-glutamate N-carboxy anhydride with amine
      terminated PEG as macroinitiator. And the benzyl group could be removed by sodium
      hydroxide. The product structure was characterized by IR, 1HNMR, GPC. The
      cisplatin-loaded micelle was observed by transmission electron microscope (TEM).
      And the block copolymer is expected to be useful as functional materials
      including carrier systems in drug controlled delivery applications.

PMID- 17002109
TI  - [Investigation of the in vivo desintegration and transit behavior of
      tetramethylpyrazine phosphate pulsincap capsule in the gastrointestinal tract of
      dogs by gamma scintigraphy].
AB  - This study aims to investigate whether a self-made novel pulsatile drug delivery
      system--razine phosphate pulsincap capsule-will achieve a pulsatile drug release
      in vivo and to study the drug release sites. A gamma scintigraphic study was
      conducted to assess the in vivo transit and release behavior of the pulsincap
      capsule with a drug tablet containing 99mTc-labeled diethylenetriamine
      pentaacetic acid (DTPA) in the gastrointestinal (GI) tract of dog. The results
      revealed that after a time interval (lag time), the drug tablet began to
      disintegrate and then released at the pylorus of stomach or in the small
      intestine of dogs with a relatively rapid release rate, which was consistent with
      the expected pulsed release pattern. The in vivo lag time of the pulsincap
      capsule in dog was shortened with the decrease of erodible plugs(EP) weight. Thus
      we can achieve a desirable lag time to meet the chronotherapeutic requirements by
      adjusting the weight of EP.

PMID- 17002110
TI  - [The experimental study of biomimetic artificial cartilage fabrication in vitro
      and ectopic chondrogenesis in vivo].
AB  - Tri-dimensional poly (DL-lactic-co-glycolic acid) (PLGA) scaffolds were
      fabricated using a rapid prototyping (RP) technique and the gene of human bone
      morphogenetic protein 2 (hBMP-2) was transferred into rabbit bone marrow stromal
      cells (MSCs) via recombinant adeno-associated virus vectors (rAAV-hBMP-2). Thirty
      two PLGA scaffolds, size (4 mm X 4 mm X 4 mm), were coated with collagen type I
      and equally divided into 2 groups. In group A, each scaffold was loaded with 2 X
      10(4) hBMP-2 (+) MSCs to establish a hBMP-2 (+) MSCs/PLGA composite. In group B,
      each scaffold was loaded with 2 X 10(4) hBMP-2 (-) MSCs to establish a hBMP-2 (-)
      MSCs/PLGA composite. The composites in both groups were cultured for subcutaneous
      implantation in nude mice. All animals were killed 30 days after implantation and
      the differentiation of composites was evaluated. As a result, MSCs infected with
      rAAV-hBMP-2 efficiently expressed hBMP-2 protein. RP-based PLGA scaffolds had
      ideal microarchitecture. The diameters of macropore and micropore of the
      scaffolds were 300 microm and 3-5 microm, respectively. At 3-5 days after
      culture, a number of seeding cells well grew on the scaffolds of both groups. The
      composites in group A had chondrogenesis ability in vivo and the expression of
      collagen type II was positive. In group B, however, only polymers and fiber
      tissues were predominantly found. The percentage of polymer remnant area was
      significantly lower in group A than in group B (P<0.01). Our results therefore
      indicate that RP-based PLGA scaffolds efficiently coated with collagen type I
      have good biocompatibility with hBMP-2 (+) MSCs and the techniques developed in
      this study may favor cartilage tissue engineering.

PMID- 17002111
TI  - [The effect of the degree of deacetylation of chitosan on the biocompatibility of
      chitosan membrane with corneal stromal cells].
AB  - Some different membranes were prepared by Chitosan with the degree of
      deacetylation (DD) of 63.7%, 73.7%, 83% and 97% respectively. To study the
      biocompatibility of Chitosan membrane toward corneal stromal cells, the rabbit
      cells were cultured on the surface of different DD chitosan membranes. The
      morphological characteristics, the cell-adhesion, the cell proliferation and the
      activity of LDH in the medium were investigated. The results of experiment shows
      that the DD of Chitosan has very significant effect on the biocompatibility of
      Chitosan membrane toward corneal stromal cells. The more DD of Chitosan, the less
      injury was made to corneal stromal cells by the chitosan membrane, which is favor
      of the growing and adhesion of corneal stromal cells. The biocompatibility of the
      membrane made with low DD Chitosan with corneal stromal cells became worse.

PMID- 17002112
TI  - [Mechanical properties and biocompatibility of nanometer calcium carbonate/poly
      (L-lactide) composites].
AB  - The purpose of this study is to synthesize nanometer calcium carbonate/poly(L
      lactide) composites and evaluate its biocompatibility, and mechanical properties.
      The nanometer calcium carbonate/poly(L-lactide) composites was prepared by the
      method of solution mixing and cell culture. Its properties were analyzed using,
      mechanical tests, MTT assay, transmission electron microscope and scanning
      electron microscope. It was found that the new kind copolymer had good
      biocompatibility, nanometer calcium carbonate could enhance the strength of the
      pure poly (L-lactide) matrix. The nanometer calcium carbonate/poly (L-lactide)
      composites is a promising bioabsorbable material. It is worth further medical
      research.

PMID- 17002113
TI  - [Preparation and characterization of magnetic nano-particles with radiofrequency
      induced hyperthermia for cancer treatment].
AB  - Mn0.5Zn0.5Fe2O4 nano-particles were prepared by the chemical co-precipitation,
      their characteristics were observed with transmission electron microscope (TEM),
      X-ray diffractometer (XRD) and thermal analysis system, and etc. The temperature
      changes of the nano-particles of Mn0.5Zn0.5Fe2O4 and its magnetic fluid explored
      in radiofrequency(RF,200 KHz, 4 KW) were measured. The proliferation ratio of
      L929 cells cultured in soak of Mn0.5Zn0.5Fe2O4 nano-particles were observed. The
      experiment indicates that the magnetic particles were about 40 nm diameter in
      average, round, had strong magnetism, and were proved to be consistent with the
      standard data of chart of XRD. Its magnetic fluid exposed to RF could be heated
      up to temperature range from 40 degrees C to 51 degrees C due to the amount of
      the magnetic nano-particles and intensity of the alternating magnetic field.
      Magnetic nano-particles were found to have no obvious cytotoxicity to L929 cells.

PMID- 17002114
TI  - [Effects of three different etching methods on surface morphology and element of
      pure titanium].
AB  - The pure titanium disks were divided into three groups and etched for 30 minutes
      with HNO3, hot H2SO4/H2O2 or hot H2SO4/HCl respectively. The treated disks were
      studied and analyzed with scanning electron microscope (SEM) and X-ray
      photoelectron spectroscopy (XPS). The disks etched with HNO3 had a smooth
      surface, while those etched with hot H2SO4/H2O2 or hot H2SO4/HCl had rough
      surfaces, and the surface etched with hot H2SO4/HCl had larger micropores. The
      XPS analysis demonstrated that the main elements of the surface in three groups
      were titanium, oxygen and carbon. The carbon concentration was the lowest on the
      surface etched with hot H2SO4/H2O2 and the highest on that etched with hot
      H2SO4/HCl. The substances were TiO2, Ti2O3, TiO and metal Ti on the surface
      etched with HNO3 or hot H2SO4/H2O2. Only TiO2 was detected on the surface etched
      with hot H2SO4/HCl.

PMID- 17002115
TI  - [Synthesis of [1,6-bis(L-alpha, beta-diaminopropionic acid) oxytocin].
AB  - A novel derivative of oxytocin containing nonprotein amino acid L-alpha, beta
      diaminopropionic acid (L-Dap) was synthesized by 7+2 fragment combination in
      solution. N beta of all the amino acid necessary was protected by carbobenzoxy
      (Z) and N beta of L-Dap was protected by tert. -butoxycarbonyl (Boc) . The
      important intermediate, heptapeptide, was synthesized by the stepwise elongation
      method using carbobenzoxy amino acid p-nitrophenyl esters in solution. Azide
      synthesis was used to get the nonapeptide. Z group was removed by treatment with
      5% Pd/C and Boc with CF3COOH. Eight new compounds incorporating L-Dap were
      obtained and confirmed by the amino acid analysis and mass spectral detection.

PMID- 17002116
TI  - [The effect of gamma-ray irradiation at low temperature on the stability and
      cytocompatibility of collagen membrane in vitro].
AB  - Membranes prepared from bovine skin collagen were exposed to 15, 25, 35 KGy gamma
      radiation respectively at low temperature. Radiation dose rate of about 22 KGy/h
      was used. The stability of the membranes was evaluated by measuring resistance of
      collagen membranes to collagenase digestion. Infrared spectra analyses of
      collagen films were performed in order to explore possible mechanisms of
      irradiation modification of collagen membranes. The results revealed that the
      degree of cross-linking and stability of collagen membranes after gamma
      irradiation were improved. The MTT assay and SEM observation of the morphology of
      L929 mouse fibroblast cells which directly cultured on the collagen membranes
      were employed to evaluate the cytocompatibility of collagen membranes treated by
      gamma-ray radiation. In the range of 0 to approximately 25 KGy irradiation dose,
      no significant difference in cytocompatibility of collagen membranes irradiated
      by gamma-ray was observed. However, when the irradiation dose was over 25 KGy,
      the cytocompatibility of collagen membranes was influenced by gamma-radiation to
      some degree.

PMID- 17002117
TI  - [The study of the in vivo-in vitro correlation of the naftopidil sustained
      release tablet in dog].
AB  - We studied the correlation of sustained-release tablet of naftopidil between the
      in vitro release and the in vivo absorption in the dog. The release rate (X) of
      naftopidil sustained-release tablet in artificial gastric fluid was determined
      and the naftopidil concentration in plasma was determined after a single oral
      dose of 100 mg naftopidil (tablet or sustained-release tablet) in the dog. The
      absorbed fraction(F) and in vivo absorption rate (A) of the NAF sustained-release
      tablet in the dog at different time were calculated by W-N method and
      deconvolution method, respectively. Then the regression equations between F or A
      and X of the corresponding time point were obtained: F=2. 1533X - 27. 636(r =
      0.9927) and A=2.3452X - 25.474(r= 0.9938). W-N method and deconvolution method
      both indicated that the correlation between the in vitro release and the in vivo
      absorption in the dog of the NAF sustained-release tablet was good.

PMID- 17002118
TI  - [Measurement of low corrosion rate of coronary stents-made of 316L and 317L
      stainless steel].
AB  - Electrochemical constant current linear polarization and atomic absorption
      spectroscopy were used to measure the corrosion rate of coronary stents made of
      316L and 317L stainless steel in 30 degrees C Tyrode's solution. The results
      indicated that the corrosion rate of 316L and 317L stainless steel was 21 X 10(
      3) microm/a, 9.8 X 10(-3) microm/a and 0.8 X 10(-3) m/a, 0.6 X 10(-3) microm/a,
      respectively. All corrosion rates were lower than the medical materials corrosion
      rate criteria, i.e. 0.25 microm/a. Moreover the corrosion resistance of 317L
      stainless steel was much higher than that of 316L stainless steel. The results
      from atomic absorption spectroscopy may correctly reflect the quantity of
      releasing metal ions in the solution.

PMID- 17002119
TI  - [Experimental study on a novel affinity adsorbent for removal of endotoxin in
      plasma].
AB  - In this paper, the adsorbent properties of Polymyxin B immobilized polystyrene
      microbeads to remove endotoxin from plasma were studied and the factors that
      affected the absorption of endotoxin were discussed. The rat models of
      endotoxemia were established, which were used in hemoperfusion. The experiment
      results indicated that the novel affinity adsorbent could remove endotoxin from
      plasma effectively. Moreover, the results also showed that Polymyxin B
      immobilized polystyrene microbeads was a fine biomaterial of hemoperfusion as
      well as exhibited a satisfactory blood compatibility.

PMID- 17002120
TI  - [Cultivation and morphological characteristics of rat adipose tissue-derived
      vascular endothelial cells in vitro].
AB  - The subcutaneous adipose tissue from the inguen of four Sprague-Dawley rats was
      obtained, then digested with one volume of collagenase type I and cultured with
      BGJb medium. The obtained adipose stromal cells were induced in human endothelial
      SFM for 7 d. The cells were observed under inverted microscope every day and
      identified by transmission electron microscope and immunocytochemical staining
      with factor VIII antigen. The results showed the induced cells uniformly had
      characteristic cobblestone morphology of endothelial cells. Factor VIII antigen
      staining was positive in cytoplasm. Under transmission electron microscope, the
      cells displayed many finger like microvilli and numerous lysosomes, mitochondria,
      a few coarse endoplasmic reticulum and Weibel-Palade bodies. The characteristics
      of the rat adipose tissue-derived endothelial cells were consistent with those of
      vascular endothelial cells derived from other tissues. It seems that subcutaneous
      adipose tissue may represent a new alternative source of endogenous vascular
      endothelial cells.

PMID- 17002121
TI  - [Study on therapeutic dosimetry of HIFU ablation tissue].
AB  - It is a difficult problem in high intensity focused ultrasound (HIFU) therapeutic
      dosimetry that how to use a BFR to ablate a mass in tissue and to determine the
      energy-efficiency relation, that is, the scale of biological effects of HIFU. A
      mass lesion was realized in this study according to a treatment principle of
      damaging tissue from BFRs to fascicle lesions, slice lesions and a mass lesion. A
      1.6 MHz transducer, 150 mm in diameter and with a focal length of 120 mm, was
      used. The focal intensities (I(SATA)) were 0-27 000 W/cm2 and the scanning speeds
      were 1-4 mm/s. The distance between every fascicle lesion was 5-10 mm and the
      distance between two slice lesions was 10-20 mm. Different irradiation depths of
      fascicle slice and mass lesion were observed after HIFU procedures in this study.
      The dosage of HIFU required for tissue coagulated necrosis was evaluated with
      energy of HIFU (J) per cubic millimeter (mm3), i.e., J/mm3 which was defined as
      energy-efficiency factor (EEF). Results showed that EEF needed for producing
      fascicle lesions increased with the increase of irradiation depth. EEF required
      for inducing various lesions in biological tissue was different. Generally, it
      followed the law: EEF(mase)< EEF(slice)<EEF(fascicle). EEF for slice lesion was
      not simply a summation of EEFs for fascicle lesions at different irradiation
      depths, although the slice lesion was assembled with fascicle lesions at
      different irradiation depths in the same treatment slice. In the same way, EEF
      for a mass lesion was not simple summation of EEFs for slice lesions at different
      layers. So HIFU therapeutic dosimetry can be carried on investigation by using
      EEF, Factors of affecting EEF of HIFU include acoustic power, exposure time,
      irradiation depth, tissue structure, and tissue functional status. Besides,
      another important factor is the change of the acoustic environment in tissue
      during the HIFU procedure.

PMID- 17002122
TI  - [Expression of isoleucine zipper modified soluble CD40L in Pichia pastoris].
AB  - To obtain the expression of Isoleucine Zipper modified soluble CD40L (IZ-sCD40L)
      in Pichia pastoris, firstly, DNA fragment of IZ-sCD40L was obtained by PCR and
      over-lap PCR . Then the expression vector pPICZaA-IZ-sCD40L was constructed.
      Nucleotide sequencing analysis indicated that the DNA fragment of IZ-sCD40L was
      correctly inserted into the pPICZaA vector. Linearized pPICZ(alpha)A-IZ-sCD40L
      was introduced into Pichia pastoris GS115. Positive clone was selected by PCR and
      its phenotype was determined. The positive clone was introduced with methanol.
      The results of SDS-PAGE and Western blot showed that product was recombinant
      Isoleucine Zipper modified soluble CD40L fusion protein.

PMID- 17002123
TI  - [Pulmonary alveolar macrophage cytotoxicity investigation of irregular shape
      mineral dusts].
AB  - In order to study the damage mechanism of mineral dusts on the pulmonary alveolar
      macrophages (AM), the changes of their death ratio, malandialdthyde (MDA) content
      and activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) were
      measured. And the technique of cell culture in vitro was used to investigate the
      cytotoxicity of six mineral dusts (twelve crystal habits) from twelve mineral
      deposits. The results showed that wollstonite and clinoptilolite had no AM
      cytotoxicity while other fibrous and grainy mineral dusts could damage pulmonary
      AM in various degrees. The cytotoxicity of fibrous mineral dusts was greater than
      that of the grainy ones, and the cytotoxicity of dusts was positively correlated
      with the active OH- content in dusts, but not necessarily so with its SiO2
      content. The high pH values produced by dust was unfavorable for the cells
      survival and the dusts with a low bio-resistance were safe for cells. The content
      of variable valence elements in dusts could influence their cytotoxicity and the
      surface charge of dusts was not a stable factor on their toxicity. It indicates
      that the shape of mineral dusts is one of the factors affecting cytotoxicity, and
      that the cytotoxicity of mineral dusts mainly depends on their properties.

PMID- 17002124
TI  - [Experimental study of non-invasive percutaneous electrical stimulator for
      treatment of obstructive sleep apnea syndrome and its clinical effect].
AB  - To study the stimulation of the genioglossus with percutaneous biphasic current
      pulses as a new therapeutical method to treat the obstructive sleep apnea
      syndrome (OSAS), polysomnography (PSG) was used to synchronously monitor the
      patient. When OSAS was occurring, the stimulation with the optimal parameter was
      given in time to make the tongue move forward, the glossopharyngeal airway
      dilated, the resistance of the upper respiratory tract reduced, the hypoxia at
      night to be improved and the sleeping structure to be ameliorated because of the
      function of the dilated muscle of the upper airway. The results of the clinical
      therapeutic effect indicated that 17 of 22 patients with OSAS had cured effects,
      2 of whom improved and 3 of whom were without effect. The effective rate was
      77.27%. It is preliminarily proved that this is a new method in the treatment of
      patients suffered from OSAS.

PMID- 17002125
TI  - [Synthesis of new gene-loaded microbubbles serve as gene delivery vehicle applied
      in reporter gene transfer into cardiac myocytes].
AB  - To improve the stability and gene-carried capability of gene-attached
      microbubbles, the method for manufacture of albumin microbubbles was modified and
      new gene-loaded microbubbles were synthesized by incorporated gene-PEI complex
      into the shell of microbubbles. Agarose gel electrophoresis and bacteria
      transformation showed that PEI had the ability to provide the protection of
      plasmid DNA from ultrasonic degradation. The new gene-loaded microbubbles
      exhibited excellent acoustical and hemorheological properties. Moreover, they
      could carry more plasmid DNA than gene-attached microbubbles. beta-galactosidase
      plasmid transfection into cardiac myocytes was performed by using ultrasound
      targeted destruction of new gene-loaded microbubbles or gene-attached
      microbubbles. Gene expression in cardiac myocytes was detected by beta
      galactosidase in situ staining and quantitive assay. It was shown that beta
      galactosidase activity in cardiac myocytes was enhanced 107-fold by ultrasonic
      destruction of gene-loaded microbubbles compared with naked plasmid transfection
      and new gene-loaded microbubbles resulted in 6.85-fold increase in beta
      galactosidase activity compared with optimal transfection mediated by gene
      attached microbubbles. These results suggested that ultrasonic destruction of the
      gene-loaded microbubbles can enhance the cardiac myocytes exogenous gene transfer
      efficiency significantly and new gene-loaded microbubbles is an efficient and
      safe gene delivery vehicle.

PMID- 17002126
TI  - [The applied research on neural network filtrated by rough-set in insect
      taxonomy].
AB  - This article provides demonstrations and calculations, using rough-set theory and
      method, of the math-morphological features (MMFs), such as form parameter,
      lobation and sphericity, etc. drawn from 28 species of insects of the Hemiptera,
      Lepidoptera and Coleoptera based on their images. The results are compared with
      statistical analysis made by Zhao Hanqing, and also with the traditional
      classifications through the pattern recognition of neural network on the basis of
      the rough-set disposal. The result of the experiments showed that when used in
      categorical taxonomy, the importance of MMF was ranked from high to low:
      (roundness-likelihood. eccentricity) > (hot-hole number, sphericity, circularity)
      > (lobation, form parameter). The results of pattern recognition by neural
      network were completely identical with those of traditional classifications.
      Accordingly, the conclusion was that this theory applied in insect taxonomy was
      more idealistic compared with statistical analysis method, and it had great
      significance when used with rough-set neural network.

PMID- 17002127
TI  - [Atherosclerotic calcification of coronary artery detected by electron beam CT: A
      new probation of calcific algorithm].
AB  - Electron beam computed tomography (EBCT) can detect the atherosclerotic
      calcification of coronary artery qualitatively and quantitatively. It was also
      verified that the atherosclerotic calcification was directly related to the
      atherosclerotic extent and had a limited relation to the occurrence of coronary
      heart disease (CHD). So EBCT is one of the good non-invasive methods for
      predicting the risk of CHD. However, there are some problems in the calcification
      parameters (calcification area, calcification score) adopted by EBCT which have
      high variability and low reproducibility. As a result, these parameters have
      imperfection and need to be improved further. This research provides a new
      calcification parameter (calcification volume) which makes the use of three
      dimensional information of all calcific pixels in EBCT scanning images of
      coronary artery. After experiment in 11 human coronary artery specimens, it was
      testified that calcification volume had a lower variability than calcification
      area and calcification score in 25% percentile, median, 75% percentile, Mean,
      respectively. P value of t test in Mean variability is 0.027, and 0.058. These
      results suggest that calcification volume may be a new calcification parameter.

PMID- 17002128
TI  - [Determination of femoral anatomic axis in robot-assisted surgery of total knee
      replacement].
AB  - Determination of femoral anatomic axis plays an important role in robot-assisted
      surgery of total knee replacement. In traditional total knee replacement surgery,
      the axis is obtained by inserting a rod into femoral lumen. However, in the robot
      assisted total knee replacement based on CT model. the femoral anatomic axis must
      be determined preoperatively. Because the lengths in femurs are quite different
      in different patients, besides noises, the upper segment and lower segment of the
      femur influence the design of the axis greatly. Traditionally, the femoral
      anatomic axis is obtained by using the least-squares method directly. However,
      this method is easily disturbed by noise. To avoid the noise disturbance of CT
      data, the least median of squares method is used to fit the femoral anatomic axis
      for its characteristic of robust regression. The least median squares method
      eliminates the disadvantage brought by the method of least squares. In finding
      the best-fit line, genetic algorithms are used in the paper. In our experiment,
      we use the proposed method to fit the femoral anatomic axis and obtain an
      excellent result.

PMID- 17002129
TI  - [The reconstruction of bioengineer active corneal stroma and its biocompatibility
      study].
AB  - This paper aims to explore the biocompatibility of bioengineer active corneal
      stroma (BACS), as the biological carrier for cornea reconstruction, to provide
      the basis for future study on clinic application. The cells and immunogenic
      components of cornea stroma were removed through different extract methods. A
      complex of functional corneal stroma cells and acellular corneal stroma was used
      to reconstruct BACS. Their morphological characteristics and ultrastructures were
      observed with transmission electron microscope. The complex was grafted into
      interlamellar stromal pockets. Cells were labeled by BrdU to examine the survival
      and conversion after grafting. The cells could survive and proliferate in
      acellular corneal stroma. All the nuclei of the corneal stromal cells showed
      positive labeling with BrdU in the BACS. After 4 weeks, BACS became transparent;
      after 8 weeks, the bioengineer active cornea stroma was fully reconstructed.

PMID- 17002130
TI  - [Speaker identification based on Mel frequency cepstrum coefficient and
      complexity measure].
AB  - In present, the most basically used parameters for speaker identification are
      linear predictive coding (LPC) parameter, Mel frequency cepstrum
      coefficient(MFCC), etc. First in this paper only MFCC was used as the parameter
      and then Lempel-Ziv Complexity was combined with MFCC as parameters. The text
      dependent recognition rate of 50 speakers increased from 42% to 80% and the text
      independent recognition rate of 50 speakers increased from 60% to 72%. This test
      shows that Lempel-Ziv complexity, as a new parameter, can be applied to speaker
      identification.

PMID- 17002131
TI  - [The preparation of a new hydroxyapatite and the study on its cytocompatibility].
AB  - The cuttlebones, harvested from cuttles, undergo the chemical reaction in high
      temperature and high pressure for a certain time. The products are qualitatively
      analysed, and spacial structure observation and cytocompatibility are tested. The
      results show that the chemical component of the cuttlebone is CaCO3 and the
      crystal type is aragonite. Cuttlebones undergo a hydro-thermal reaction, and thus
      transform into hydroxyapatite-that is, the cuttlebone-transformed
      hydroxyapatite(CBHA). The CBHA materials have the interconnected microporous
      network structures. Under the high magnification, CBHAs appear to have many micro
      spheres, thus construct a new self-assembled nano-material system. The marrow
      stromal osteoblasts can adhere to and proliferate well on the surface of the
      CBHAs. These results show that CBHAs have good biocompatibility. Therefore, it
      can be a potential candidate scaffold for bone tissue engineering.

PMID- 17002132
TI  - [Medical image segmentation techniques].
AB  - Medical image segmentation is an important application of image segmentation.
      However it is the bottleneck that restrains medical image application in clinical
      practice. In this paper, the aim and significance of medical image segmentation
      are discussed, the development of medical image segmentation techniques is
      sketched, and a review of the medical image segmentation techniques is given.

PMID- 17002133
TI  - [Research progress of the drug screening technology in type 2 diabetes mellitus].
AB  - With the incidence of type 2 diabetes mellitus increasing year after year, the
      technology of drug screening of type 2 diabetes mellitus progress rapidly, from
      the level of animal screening to cellular and molecular screening model, from the
      traditional drug screening technology to high efficient and throughput screening.
      This paper will summarize the technology of drug screening in the therapy of type
      2 diabetes mellitus.

PMID- 17002134
TI  - [Visualization of neuronal fiber tracts in white matter based on diffusion
      tensor].
AB  - In this paper, the basic principal or rational of diffusion tensor imaging (DTI),
      which develops rapidly in the field of functional magnetic resonance imaging
      study, is introduced. And how to reconstruct the imaging of neuronal fiber tracts
      in white matter with the data of DTI is described. The technique of tractography,
      its advantages and disadvantages are analyzed. Finally, the limitations and
      further applications of neuronal fiber tracts visualization are discussed.

PMID- 17002135
TI  - [The research advances of biomechanics of human knee joint ligaments].
AB  - Ligaments are the main parts which stabilize the knee joint. How to analog the
      ligaments in biomechanical model will affect the characteristics of the human
      knee dynamics and in the computation of the stress in ligaments between two
      bones. This symposium is aimed at the survey of the simplified method of the
      ligaments via mechanical parameters, and providing an exact method of
      constructing model.

PMID- 17002136
TI  - [Strategies for antibody immobilization during the fabrication of antibody
      microarrays].
AB  - As one of the proteomic technologies, antibody microarrays can provide a powerful
      tool for the high-throughput parallel analysis of thousands of proteins in a
      single experiment. Because antibodies are chemically and structurally complex;
      immobilizing antibody on solid phase surface of substrates has been a key step
      during the development of antibody microarrays. This review will focus on the
      current strategies for antibody immobilization and discuss the advantages and
      disadvantages of these methods.

PMID- 17002137
TI  - [Research advances in the controlled release of growth factor related to blood
      vessel tissue engineering].
AB  - Growth factors play an important role in cell adhesion and proliferation as well
      as in tissue regeneration. By incorporating growth factors into polymer
      scaffolds, controlled release of them can be performed. The release mechanism is
      varied with the incorporation methods. In this paper, the latest advances in the
      controlled release of growth factors by blending, hydrogel, microsphere embedding
      and chemical bonding are reviewed. The potential application of ultrafine fibric
      embedding in growth factor delivery is described as well.

PMID- 17002139
TI  - [Features and clinical application of acoustic parameters in voice].
AB  - In order to study laryngeal phonic function, the methods of acoustic evaluation
      and phonatory detection has become the focused problem by doctors in
      otorhinolaryngology and speech pathology. A great number of acoustic parameters
      have been designed and used. This article intends to discuss objective rated
      indexes reflecting the functional condition of vocal cords.

PMID- 17002138
TI  - [Ras-MAPK signaling pathway activated via brain-derived neurotrophic factor].
AB  - Brain-derived neurotrophic factor (BDNF)is the richest neurophin in brain tissue
      and may act as an activity-dependent neuronal survival factor. In vitro, BDNF
      plays an important role in preventing cortical neurons from hypoxia-induced
      neurotoxicity. It could induce a variety of cellular responses such as cell
      growth, survival, differentiation, and anti-apoptosis mainly via activating
      mitogen-activated protein kinase (MAPK) and Ca2+/calmodulin-dependent kinase
      (CaMK) signaling pathways. And among these multiple signaling pathways there is
      growing evidence of complicated cross talk.

PMID- 17002140
TI  - The history of mobile-bearing total knee replacement systems.
AB  - The use of a mobile-bearing knee system is routine in modern total knee
      arthroplasty (TKA). There are indications for use of a mobile-bearing TKA for a
      growing number of patients. The design, however, was not always well appreciated.
      Fears of perioperative difficulties and lack of understanding of the design
      principles limited the acceptance of mobile-bearing technology. Recent evidence
      has shown that use of mobile-bearing prostheses in TKA has increased, and today,
      nearly three decades after its introduction, the mobile-bearing design remains
      relavent and important. The theories behind the design of mobile-bearing
      prostheses have shown in clinical practice what many already believed to be true:
      mobile-bearing TKA, when performed correctly, is reliable, and capable of
      providing substantial benefit for patients.

PMID- 17002141
TI  - Trends in total knee arthroplasty.
AB  - The success of total knee arthroplasty (TKA) over the past two decades of use has
      resulted in the implantation of TKA into younger patients who have increased
      functional requirements and demand increased implant longevity. Improved
      functional performance requires enhanced range of motion, increased motor
      performance, and creation of kinematic patterns that more closely resemble the
      normal knee. Increased longevity necessitates more durable implant fixation,
      improvements in bearing materials, and lower polyethylene stresses.
      Considerations to reduce polyethylene wear include increased cross-linking,
      improved femoral component surface finish, better modular tibial locking
      mechanisms, and the use of mobile-bearing TKA designs that allow increased
      implant conformity and reduced contact stresses without increasing loads
      transmitted to the fixation interface.

PMID- 17002142
TI  - Evolution of the low contact stress (LCS) complete knee system.
AB  - The low contact stress knee design was one of the first designs to become widely
      available and popular for total knee arthroplasty. The low contact stress knee
      was initially designed to address wear due to high contact stresses seen in fixed
      bearing designs. Today, nearly 30 years after its introduction, the technology
      behind the knee remains just as relevant. Many of the original innovations in
      early low contact stress knee systems are still in use today. New innovations,
      like a new instrument set and the advent of computer-assisted surgery, have added
      to the success of the technology. The history of this innovative design is
      discussed with special consideration given to the specific design principals that
      have improved the basic design over the past three decades.

PMID- 17002143
TI  - Rationale for the posterior-stabilized rotating-platform knee.
AB  - The nonposterior-stabilized mobile-bearing knee and the posterior-stabilized
      fixed-bearing design have been successfully used for the past three decades.
      Lessons learned from their use have culminated in the design of a posteior
      stabilized mobile-bearing knee that incorporates beneficial features of both. The
      posterior-stabilized mobile-bearing knee is aimed at addressing polyethylene wear
      issues related to the fixed-bearing design, and improve upon stability and range
      of motion typical of nonposterior-stabilized mobile-bearing knee designs.

PMID- 17002144
TI  - The P.F.C. sigma RP-F total knee arthroplasty: designed for improved performance.
AB  - The new P.F.C. Sigma RP-F (rotating-platform high-flexion) knee has been designed
      to permit 155 degrees of flexion after total knee arthroplasty (TKA) without
      compromising wear, polyethylene contact stresses, patellofemoral tracking, or
      stability. The purpose of this article is to describe the design features of the
      P.F.C. Sigma RP-F TKA. It is our belief that future primary posterior-stabilized
      TKA will incorporate many of the design features of the RP-F knee for improved
      performance.

PMID- 17002145
TI  - Implant sizing of the P.F.C. sigma rotating-platform total knee system.
AB  - We studied the P.F.C. Sigma rotating-platform total knee arthroplasties performed
      during 2004 and 2005 to assess implant size variations in men versus women and
      size variation in bilateral knees. We subsequently studied commercial femoral
      radiograph templates to compare mediolateral and anteroposterior dimensions.
      Sixty-four percent of women more frequently had a tibial tray one size smaller
      with respect to the femur and 63.5% of men had the same-sized femur and tibia.
      Bilateral knees were the same size in both sides 97% of the time in women, and
      90% in men. The template comparison found that the P.F.C. Sigma rotating-platform
      femur had a mediolateral dimension that was smaller than many knee replacements
      commercially available.

PMID- 17002146
TI  - Wear-simulation analysis of rotating-platform mobile-bearing knees.
AB  - The wear and wear debris from rotating-platform mobile-bearing knees and fixed
      bearing knees were compared in knee joint-simulator studies. The wear rate of the
      fixed-bearing knees was found to increase as the kinematics were increased
      because of an increase in internal-external rotation and an increase in
      anterorposterior (AP) translation. The wear rate of the rotating-platform mobile
      bearing knees was found to be significantly lower than that of the fixed-bearing
      knees. The rotating-platform mobile-bearing knee was able to decouple the complex
      kinematics to pure rotation at the inferior tibial articulating surface and
      linear flexion-extension and AP sliding at the superior femoral articulating
      interface, substantially reducing cross-shear and wear. No difference was found
      in the wear debris between the rotating-platform and fixed-bearing knees. This
      resulted in a substantially reduced functional biological activity or osteolytic
      potential for the rotating-platform mobile-bearing knees due to the lower wear
      rates.

PMID- 17002147
TI  - Clinical results of primary low contact stress cementless total knee
      arthroplasty.
AB  - The published clinical and radiographic outcomes data for primary cementless low
      contact stress (LCS) total knee arthroplasty (TKA) were examined. The majority of
      patients (92.6%) were pain free or had only mild pain, and excellent or good knee
      scores (99.1%) at follow-up. Patella difficulties and significant radiolucent
      lines were rare, occurring in less than 1% of patients. The average range of
      motion (ROM) for patients without a history of previous knee surgeries was 112.1
      degrees. Previous knee procedures had a negative impact on ROM. Overall, primary
      cementless LCS TKA achieves excellent clinical nd radiographic results.

PMID- 17002148
TI  - Importance of a balanced-gap technique in rotating-platform knees.
AB  - Rotating-platform knees are constructed of highly conforming polyethylene to
      reduce contact pressures that potentially cause wear. The mobile nature of the
      rotating platform can lead to bearing spin-out. The purpose of this study was to
      determine the prevalence of spin-out in a single series. A total of 426 knees in
      393 patients were included in the study. All knees were implanted using a
      balanced-gap technique. The average follow up was 3.2 years. There were no cases
      of bearing spin-out. The author concludes that the balanced-gap technique
      reliably prevents spin-out in mobile-bearing total knee implantation. This
      implantation technique provides the potential wear benefits of the rotating
      platform design with a nominal bearing spin-out rate.

PMID- 17002149
TI  - The P.F.C. sigma RP-F TKA designed for improved performance: a matched-pair
      study.
AB  - The press fit condylar P.F.C. Sigma RP-F (rotating-platform, high flexion) knee
      is designed to provide a range of motion (ROM) of 155 degrees without
      compromising wear, polyethylene contact stresses, patellofemoral tracking, or
      stability. The first 50 TKA surgeries using the Sigma RP-F knee performed at the
      author's institution were matched to 50 rotating-platform knees for age, sex,
      body mass index, preoperative diagnosis, duration of follow-up, and preoperative
      ROM to determine the effect of design on postoperative ROM. The mean increase in
      active ROM in the Sigma RP-F group was 17 degrees, compared with 6 degrees in the
      rotating-platform group (P =.0011). The mean increase in active ROM in patients
      who had less than 120 degrees of preoperative motion was 27 degrees in the Sigma
      RP-F group, compared with 16 degrees in the rotating-platform group (P = .006).
      With the new P.F.C. Sigma RP-F design, greater ROM can be achieved independent of
      preoperative ROM.

PMID- 17002150
TI  - The need for gender-specific prostheses in TKA: does size make a difference?
AB  - Aging boomers and younger patients requiring total knee arthroplasty demand
      and/or expect better function, improved durability, and a quicker recovery. In
      response to this demand, surgeons are modifying surgical techniques, and industry
      is examining implant design. One proposal is the gender-specific implant, but the
      development of separate systems for men and women may prove to be unnecessary.

PMID- 17002151
TI  - Ligamentous balancing in rotating-platform knees.
AB  - The primary objectives of total knee arthroplasty are to reduce pain, maximize
      range of motion (ROM), and provide stability through the gait cycle. Pain relief
      depends on proper ligamentous balancing and solid implantation. Solid
      implantation is typically assured through cementation, whereas soft-tissue
      balancing is vital to ensure maximum ROM and stability. Special consideration
      should be given to obtaining proper axial alignment, symmetric tension on the
      ligaments in both flexion and extension, and equalizing the flexion extension
      gaps. Strategies to ensure proper alignment and ligamentous balancing
      intraoperatively are discussed.

PMID- 17002152
TI  - Management of the severe varus and valgus knee using the low contact stress
      rotating platform.
AB  - Many surgeons feel the use of an unconstrained mobile-bearing knee is
      contraindicated in cases of severe varus and valgus deformity. In the author's
      opinion the Sigma LCS rotating-platform knee system can be used in virtually
      every primary knee irrespective of deformity. The key is to maintain flexion
      stability by not releasing the lateral collateral ligament in a valgus knee or
      the superficial medial collateral ligament in the varus knee.

PMID- 17002153
TI  - Surgical technique tips and pearls in rotating-platform knee arthroplasty.
AB  - Rotating-platform mobile-bearing knee arthroplasties have potential advantages
      over fixed-bearing knee prostheses that may lead to better long-term wear of the
      polyethylene articulation. Their potential disadvantages include bearing spin-out
      that is usually the result of a tight posterior cruciate ligament in need of
      release. The "slide-back test" can help determine this need during placement of
      the trial components. Clearing polymerized cement from the back of the knee can
      be difficult during rotating-platform knee arthroplasty unless cementing is
      completed using a trial tibial insert without a stem. Exchanging a rotating
      platform insert at a future arthrotomy can be facilitated by the use of a shim
      that provides exposure to the polyethylene tibial post that articulates within
      the stem of the tibial tray. Severing the post allows extraction of the
      polyethylene plateau and access to the post within the tray.

PMID- 17002155
TI  - Optimizing range of motion in cruciate-retaining mobile-bearing tka: experience
      with 2000 cases.
AB  - We describe experience with 2000 cruciate-retaining Sigma RP total knee
      arthroplasties performed between September 2000 to January 2006. All procedures
      were performed with a midvastus arthrotomy, medioposterior release, and posterior
      condylar clean-out technique. This implant design uses a congruent polyethylene
      bearing to diminish contact stress while allowing rotation between the
      polyethylene bearing surface and tibial tray. Of the 2000 knees, 1596 had follow
      up data at one year. Seven hundred-twenty-seven had an average flexion of 123
      degrees, 692 had an average Knee Society Score of 94, and 672 had an average
      function score of 86.

PMID- 17002154
TI  - Patellar crepitation in the P.F.C. sigma total knee system.
AB  - Painless and painful patellar crepitation and patellar clunk syndrome represent a
      spectrum of peripatellar scar formation particular to posterior-stabilized knee
      components, although it may occur with cruciate-retaining designs as well. The
      formation of peripatellar inflammatory scar tissue is related to implant design
      and surgical technique, with microscopic and gross findings indicating varying
      degrees of inflammatory fibrous hyperplasia. These well recognized clinical
      entities have an incidence ranging between 1% and 5% in different series. The
      majority of patients with mildly painful or painless patellar crepitation will
      improve within 6 months to 1 year. In patients with more disabling symptoms such
      as catching, early intervention with open scar excision should be considered.

PMID- 17002156
TI  - High-flexion rotating-platform knees: rationale, design, and patient selection.
AB  - High flexion in total knee arthroplasty (TKA) is any flexion beyond 125 degrees.
      High-flexion activities such as kneeling or praying are done with internal
      rotation, external rotation, and in neutral. Therefore, maximum flexion TKA
      requires a rotating platform. Superior range of motion (ROM) and fluoroscopic
      kinematics of femoral roll-back have been shown with the P.F.C. Sigma RP
      posterior-stabilized knee. This knee was modified to reduce the P.F.C. Sigma RP
      F, a maximum flexion knee, by adding a third contact area at the post-cam
      mechanism to significantly increase bearing conformity and decrease polyethylene
      stresses in the range of 125 degrees-155 degrees. Clinical experience is reported
      with statistically significant increases in postoperative ROM in patients with
      the P.F.C. Sigma RP-F. Patient selection criteria for the P.F.C. Sigma RP-F
      include patients with high-flexion lifestyles, younger, more active patients
      demanding a better ROM, and those patients with less than 100 degrees
      preoperative ROM. This knee system shows significant promise in providing maximum
      flexion, and system longevity is expected.

PMID- 17002157
TI  - Total knee arthroplasty with modular rotating-platform hinge.
AB  - Third-generation modular rotating hinged knee systems are now widely available.
      The S-ROM rotating hinge features slotted and splined stems for torsional
      stability, and metaphyseal filling and loading sleeves for the bony defects
      encountered in revision total knee arthroplasty (TKA). Primary indications for a
      hinge include medial or lateral collateral loss, massive bone loss, and
      metaphysis and cortical shell, which includes collateral origins or insertions,
      and severe flexion gap imbalance requiring a link system for stability.
      Indications for a hinge in primary TKA include patients with neuromuscular
      deficits such as polio or flail knee, who require the hyperextension stop.
      Reported midterm results are excellent with no mechanical failures and positive
      bone remodeling in 65 patients.

PMID- 17002158
TI  - Tibial post impingement in posterior-stabilized total knee arthroplasty.
AB  - Posterior-stabilized total knee arthroplasty (TKA) has enjoyed documented long
      term success. Few complications related to tibial post failure have been
      documented. Impingement between the tibial post and femur has been implicated in
      failure and increased wear. Issues of surgeon component placement, design, and
      kinematics are discussed in relation to the tibial post in osterior-stabilized
      TKA.

PMID- 17002159
TI  - Low contact stress (LCS) complete knee system in revision surgery.
AB  - Revision total knee arthroplasty (TKA) should offer the same benefits to patients
      as primary TKA. As in primary TKA, a main objective of revision TKA is to reduce
      pain and restore functional range of motion. There are several potential causes
      of total knee failure, but the principles of repairing each of them is similar.
      The long-term success of the low contact stress knee system in primary TKA is
      well established, and clinical evidence for revision TKA with the low contact
      stress knee is promising.

PMID- 17002160
TI  - [PPAR agonists do not come up to expectations. Hope about the preventive effect
      in type 2 diabetes has come to nought].

PMID- 17002161
TI  - [Lipid-lowering cardiovascular prevention in type 2-diabetes. Statins are
      effective according to the FIELD study].

PMID- 17002162
TI  - [Attending physician must consider uncertainty. Don't let yourself be cheated by
      the numbers!].

PMID- 17002163
TI  - [Trauma care in the Southern region scrutinized. Peer review system for better
      care].

PMID- 17002164
TI  - [Small bowel tumor common cause of obscure gastrointestinal hemorrhage. The
      highest risk among elderly men].

PMID- 17002165
TI  - [Nosocomial infections with multiresistant bacteria--not only staphylococci].

PMID- 17002166
TI  - [Different course literature. Reading fiction a part of medical education in
      Linkoping].

PMID- 17002167
TI  - [A teetotaller rejected by alcohol ignition interlock].

PMID- 17002168
TI  - [How to learn physicians communicable skills?].

PMID- 17002169
TI  - [Avoiding HIV infection must be the message].

PMID- 17002170
TI  - [The most important cause of HIV/AIDS is poverty].

PMID- 17002171
TI  - [Low TSH seems to have a depressing effect on autoimmunity].

PMID- 17002172
TI  - [Primary sclerosing cholangitis could have been the cause of Beethoven's death].

PMID- 17002173
TI  - [The pitfall of innovation].

PMID- 17002174
TI  - [COPD--chronic obstructive pulmonary disease and its implications for the human
      organism].
AB  - Chronic obstructive pulmonary disease (COPD) belongs next to bronchial asthma to
      the most important diseases of the respiratory tract in terms of its socio
      economic impact. Especially exacerbations of COPD and clinical end-stages exert
      extremely negative effects on the global burden of disease. This article analyses
      current aspects of COPD regarding epidemiology, pathogenesis, pathophysiology and
      diagnosis of the disease. Given the estimation that COPD will be the third most
      common cause of death in the year 2020, the high socio-economic costs and the
      primary cause tobacco smoke exposure, the disease can be regarded as extremely
      relevant for numerous aspects of insurance medicine.

PMID- 17002175
TI  - [Disability in lupus erythematosus].
AB  - Morbidity and co-morbidities in patients with lupus erythematosus (LE) result in
      an impairment, limiting activities of daily living. We compared the handicap,
      appraised by the German welfare system in patients with LE and their diagnosis,
      morbidities and co-morbidities, therapy, functional capacity, psychological
      status and general health. The data were obtained in an anonymous self
      administered questionnaire conducted by the lupus patient association. 892 data
      sets were available for the trial. The mean age was 46.9y, disease duration was
      10.3y. The patients had 3.8 concomitant diseases on average. 39.7% were still
      working and 35.4% drew a pension. 59.2% made an application for disability, which
      wasn't assigned in only 2.5% of cases. 82.6% had an average grade of disability
      of more than 50%. It demonstrated a good correlation to age, disease duration,
      type of LE and therapy. Predictors for a worse assessment were disease duration,
      osteoarthritis, cerebral insults and functional capacity. In conclusion the data
      demonstrate a fair appraisal of disability by the German welfare system in
      patients with LE. Self-administered questionaires can yield credible results.

PMID- 17002176
TI  - [Questionable procedures in environmental medicine using an example of "multiple
      chemical sensitivity"].
AB  - "Multiple Chemical Sensitivity" (MCS) has to be regarded as a merely subjective
      concept without etiological and pathological background or objective criteria for
      diagnosis. Most of the "MCS" patients suffer from various psychiatric disorders;
      in a small minority somatic diseases can be found. The data recently won in the
      German multicenter study on MCS underline this point of view. The informal German
      "MCS network" consisting of patients' self-help groups, "therapists" with or
      without medical background and law firms specialised in compensation claims
      nevertheless strictly denies any psychogenic model. They do, however, propose a
      whole range of diagnostic and therapeutic procedures based on different
      theoretical concepts. Some of the procedures are derived from scientifically
      based medicine, others have an unconventional and esoteric background. Most of
      them are logically incompatible; however, they are applied in a polypragmatic
      manner. None of these so-called diagnostic or therapeutic procedures or health
      technologies can be regarded as evidence-based. Some of them, however, are
      extremely expensive and/or pose significant risks for patients' health. In any
      case, wrong subjective disease concepts are perpetuated iatrogenically.
      Additionally, those procedures make effective help for the real underlying
      medical and/or psychiatric conditions impossible.

PMID- 17002177
TI  - [Costs of diabetes mellitus type 2 and self measurement of blood glucose in
      Germany].
AB  - It is extremely difficult to assess the prevalence and the total costs of
      diabetes mellitus for the German health care system. The last sound assessment of
      the total costs is based on the CODE-2 study, although this study reflects the
      situation in 1998. METHODS: In this paper we assess again the total costs of
      diabetes mellitus type 2 and self measurement of blood glucose (SMBG) for the
      German healthcare system, based on the analysis of a recently published
      retrospective, multicentre trial dealing with the impact of SMBG on long-term
      patient outcomes. RESULTS: Overall, yearly costs for the treatment of diabetes
      mellitus type 2 and its complications amount to Euro 3 196,-per patient. This
      equals 4.6% to 8.2% of the German healthcare expenditure, in relation to the
      estimated prevalence of the disease in Germany. The cost difference between the
      cohorts with and without SMBG was not essential (Euro 290,-higher costs in the
      cohort with SMBG). CONCLUSIONS: From a public health standpoint, prevention of
      diabetes mellitus or at least prevention of its complications by optimising
      glucose metabolism should be given highest priority in times of limited resources
      for healthcare. SMBG is perhaps a valuable tool to achieve this target.

PMID- 17002178
TI  - [Significance of outcomes research for health insurance].
AB  - Innovation is an important stimulus of the economy and the healthcare system. Two
      components may inhibit innovations, an increased risk of the developers to market
      their innovations and an increased risk of the public to increase the costs due
      to uncontrolled use of innovations. New information can contribute to controlling
      both risks. We use the term "outcomes research" to describe the new working field
      that generates this information. The need for outcomes research is described. To
      differentiate clinical research from outcomes research, we demonstrate that these
      two fields of research pursue different goals, use different methods, and finally
      generate different types of results.

PMID- 17002179
TI  - [Biochips--progress and progress pitfalls?].

PMID- 17002180
TI  - [The downward spiral in medication approval].

PMID- 17002181
TI  - [Complementary medicine: is proof of effectiveness really necessary?].

PMID- 17002182
TI  - [Misinterpreted lymphadenopathy and thrombocytopenia as unrecognised initial
      symptoms of an HIV-infection].
AB  - In a 28-year-old woman and a 30-year-old man with lymphadenopathy, shown by
      histopathology to be follicular hyperplasia, and in a 40-year-old woman and a 40
      year-old man with a thrombocytopenia, HIV-infection was not diagnosed until years
      later. Three of the four patients did not belong to a 'classical high-risk group'
      for HIV/AIDS. All patients, meanwhile, suffered from minor or major
      complications. Moreover, the number of CD4+ cells had decreased to < or =
      200/microl before antiretroviral therapy was started. After treatment, all four
      patients were in reasonable to good condition. An HIV-infection should be
      considered in every case of reactive lymphadenopathy or thrombocytopenia.

PMID- 17002183
TI  - [Healthcare for asylum seekers and refugees: our country can do better].
AB  - The article 'Mental and physical health problems of and the use of healthcare by
      Afghan, Iranian and Somali asylum seekers and refugees' in this issue shows, as
      expected, that the health status of all three groups is poorer than that of the
      Dutch population. Even worse is that the care offered is far from optimal. To
      interpret these results, it would be important to know who the asylum seekers and
      refugees are in comparison with their fellow countrymen in their countries of
      origin, to have a better understanding of the background of their health
      problems, and to view the care offered to these people critically. Since they are
      a very heterogeneous and relatively small group, it is not easy to organise
      appropriate care for asylum seekers and refugees. Although attempts are being
      made to improve the situation, Dutch society should invest more so as to provide
      the same quality of care to its guests as it provides for its own population.

PMID- 17002184
TI  - [Combating infectious disease using mathematical modelling].
AB  - When determining interventions against threatening infectious diseases such as
      HIV-infection, severe acute respiratory syndrome (SARS), smallpox and pandemic
      influenza, the use of mathematical models of the spread of infectious diseases is
      becoming increasingly popular. These models contribute to the structuring of the
      knowledge already available in various disciplines, to finding epidemiological
      connnections, to demonstrating lacunas within the pool of knowledge and to the
      comparison of the expected effects and costs of preventative and intervention
      measures. The use of models leads to a 'made-to-measure' analysis ofthe effects
      and costs of preventative and intervention measures which takes account of the
      specific characteristics of infectious diseases. The integration of knowledge
      from various disciplines can be supported by more research into the theoretical
      epidemiology of infectious disease and by better integration of mathematical
      models into policy development. The resulting and better foundations of this
      policy that are achieved by means of infectious disease modelling translate into
      more effective combating of infectious disease.

PMID- 17002185
TI  - [Melatonin: physiological and pathophysiological aspects and possible
      applications].
AB  - The number of indications for the medical use of melatonin is slowly increasing.
      Melatonin is produced by the pineal gland and is a key signal in the circadian
      rhythm of the body. Melatonin plays an obvious role in the pathophysiology and
      treatment of sleep disorders and jetlag. Recent research has also demonstrated
      its favourable effect on blood-pressure regulation. By analogy, melatonin may
      play a role in a variety of other circadian processes. However, research into the
      precise effects is still insufficient.

PMID- 17002186
TI  - [The practice guideline 'vitiligo'].
AB  - A working group of the Dutch Society for Dermatology and Venereology (NVDV), in
      collaboration with the Dutch Institute for Health Care Improvement (CBO), has
      written an evidence-based guideline for the treatment of vitiligo. A distinction
      is made between generalised or non-segmental vitiligo and localised, including
      segmental, vitiligo. In patients with generalised vitiligo phototherapy
      (especially narrow-band ultraviolet B) is the treatment of first choice while in
      localised vitiligo, this is surgery, particularly autologous skin transplantation
      (Thiersch grafting, the use of blister epidermis and cell suspensions). However,
      on the basis of the results of the treatments proposed in the guideline, the
      working group cannot advise dermatologists to propose a particular treatment to
      each vitiligo patient they see. On the other hand, the working group is of the
      opinion that, based on a proper medical examination and an assessment of the
      disease burden, well-considered advice--and in some cases therapy--should be
      given to every vitiligo patient who requests it. The benefit of the guideline is
      that it provides clarity to dermatologists, general practitioners and patients
      regarding the therapeutic possibilities and limitations.

PMID- 17002187
TI  - [Diagnostic image (290). A woman with painful finger joints and swelling].
AB  - A 38-year-old woman with chronic pain of and swelling located at the proximal
      interphalangeal (PIP) finger joints suffered from 'knuckle pads' or 'Garrod's
      fatty pads'.

PMID- 17002188
TI  - [Mental and physical health problems of, and the use of healthcare by, Afghan,
      Iranian and Somali asylum seekers and refugees].
AB  - OBJECTIVE: To estimate the prevalence rates of mental and physical health
      problems and the use of healthcare services among adult asylum seekers and
      recognised refugees from Afghanistan, Iran and Somalia in the Netherlands.
      DESIGN: Cross-sectional study. METHOD: Asylum seekers were approached in 14
      reception centres and refugees were interviewed in 3 municipalities (Arnhem,
      Leiden and Zaanstad). Respondents were interviewed in their own language and
      asked questions pertaining to: general health, chronic complaints, symptoms of
      post-traumatic stress disorder (PTSD), symptoms of depression/ anxiety, the use
      of healthcare services (general practitioner, medical specialists,
      hospitalisation, mental-health services, medication) and background variables.
      RESULTS: A total of 232 asylum seekers and 178 refugees participated (response
      rates of89% and 59%, respectively). Of these, 142 (61%) and 99 (56%),
      respectively were males and the average age was 34.4 (SD: 11.o) and 40.3 (SD:
      13.3) years, respectively. Compared to refugees, asylum seekers more often
      considered their health to be poor (42% and 59%, respectively), had more symptoms
      of depression/anxiety (39% and 68%, respectively), and had more symptoms of PTSD
      (11% and 28%, respectively). No differences were found between refugees and
      asylum seekers in the self-reported use of healthcare services. CONCLUSION: This
      study showed that asylum seekers have more health problems than refugees, but
      that there are no differences in the self-reported use of healthcare services.
      More research is needed to answer the question ifasylum seekers have sufficient
      access to the healthcare system.

PMID- 17002189
TI  - [Submucosal lipoma of the colon: abdominal cramps with rectal bleeding and weight
      loss].
AB  - An 81-year-old woman had abdominal cramps, rectal bleeding since 2 weeks and
      weight loss. Colonoscopy showed an ulcerating tumour of about 4 cm in the
      transverse colon. Pathological examination of biopsies taken during colonoscopy
      indicated moderately active chronic colitis. Based on the colonoscopy findings,
      the tumour appeared to be malignant and laparotomy was performed and the
      transverse colon was resected. Pathological examination of the resected lesion
      revealed a submucosal lipoma. The patient recovered fully. Lipomas account for 4%
      of benign gastrointestinal tumours and 90% of lipomas are submucosal. Their
      presentation is often similar to malignant tumours. The naked fat sign after
      biopsy and the elasticity of the lesion are typical features encountered during
      colonoscopy. Given the high fat content of these lesions, they are easily
      discernible with CT and MRI. Lipomas with a diameter < 2 cm can be safely removed
      endoscopically. Larger lesions should be removed by segment resection.

PMID- 17002190
TI  - [Thalidomide for the treatment of recurrent gastrointestinal blood loss due to
      intestinal angiodysplasias].
AB  - Two female patients, 86 and 80 years of age, had been treated with blood
      transfusions for several years and several months, respectively, due to iron
      deficiency anaemia caused by gastrointestinal blood loss. Angiodysplasias were
      detected and subsequently coagulated in the course of repeated gastroscopies and
      colonoscopies. Due to the failure of this treatment, treatment with thalidomide
      was started. Thereafter, the gastrointestinal bleeding stopped and there was no
      longer any need for blood transfusions. Treatment with thalidomide seems an
      effective therapy for patients with frequently recurring gastrointestinal blood
      loss due to angiodysplasias who no longer tolerate conventional and invasive
      procedures due to their physical condition.

PMID- 17002191
TI  - [Diagnostic image (275). A man with acute shoulder pain followed by shoulder
      weakness].

PMID- 17002192
TI  - [University teaching hospitals should no longer hold primacy in graduate medical
      education].

PMID- 17002193
TI  - [The guideline 'Treatment of acute carbon-monoxide poisoning' from doctors in
      clinics with a tank for hyperbaric ventilation].

PMID- 17002194
TI  - What drives donor funding in population assistance programs? Evidence from OECD
      countries.
AB  - The 1994 International Conference on Population and Development (ICPD)
      established goals for the expansion of population assistance. To date, the
      financial promises made by donor countries in 1994 have not been met. To unravel
      the gap between ambitions and contributions, we use panel estimation methods to
      see what lies behind the level of donor contributions and the sharing of burdens
      across the various categories of population and HIV/AIDS assistance in 21 donor
      countries for the years 1996-2002. Contributions by donors depend heavily on the
      economic wealth and subjective preferences of donor countries. The sharing of the
      ICPD burden within the group of OECD/DAC countries is in line with the countries'
      ability to pay, although within the aggregate we observe a specialization in
      channels for aid: small countries predominantly use multilateral aid agencies,
      whereas large countries rely more on bilateral aid channels. Catholic countries
      are averse to donating unrestricted funds (flowing primarily to multilateral
      agencies) or restricted funds targeted at family planning programs.

PMID- 17002195
TI  - Challenges to integrating sexual health issues into reproductive health programs
      in Uzbekistan.
AB  - This study examines the direction and result of efforts of nongovernmental
      organizations (NGOs) in the area of reproductive and sexual health in Uzbekistan.
      It focuses specifically on the institutional, structural, epidemiological, and
      cultural forces responsible for the exclusion of sexual health issues from
      reproductive health campaigns in the most populous Central Asian country. In
      Uzbekistan, as in other countries of the region, significant international
      support was given to NGOs providing reproductive health services in the mid-to
      late-1990s, well into the early period of the HIV/AIDS pandemic and after the
      1994 mandate of the International Conference on Population and Development for
      the inclusion of sexual health as a key reproductive health component. Examining
      the exclusion of sexual health issues from reproductive health campaigns in
      Uzbekistan highlights problems relating to time lags in program and evaluative
      development and the difficulties NGOs experienced in balancing donor-state
      agendas with recipient-state priorities. Findings question standard assumptions
      regarding the advantageous structural aspects of NGOs, in terms of flexibility,
      responsive agenda generation, and state independence.

PMID- 17002196
TI  - Advanced methods for evaluating the impact of family planning communication
      programs: evidence from Tanzania and Nepal.
AB  - Evaluations of national family planning communication campaigns are often
      complicated by nonrandomized research designs and self-reported measures of
      exposure to media messages, both of which can bias estimates of campaign
      effectiveness if suitable analytical methods are not employed. This study uses
      three methods to address these problems: (1) single-equation multiple regression
      analysis; (2) propensity score matching (PSM); and (3) maximum-likelihood
      simultaneous equation models (SEM), namely bivariate probit. We use these methods
      to evaluate the impact of family planning health-communication campaigns on the
      use of modern family planning methods, focusing primarily on the radio drama
      Zinduka! in Tanzania and Ghanti Heri Haad Nilaun in Nepal. We find that these
      methods led to substantially different estimates of the magnitude of the impact
      of these communication campaigns. Specifically, we found that self-reported
      exposure to each radio program was exogenously related to family planning use and
      that PSM and multiple regression analysis gave similar estimates in those
      situations. An indicator of exposure to any type of family planning message was
      found to be endogenous, in which case bivariate probit and PSM gave different
      estimates of program impact. Researchers should, therefore, pay close attention
      to the results of tests for endogeneity and identification that guide the
      appropriate use of the different methods.

PMID- 17002197
TI  - Emergency contraception in Honduras: knowledge, attitudes, and practice among
      urban family planning clients.
AB  - Emergency contraception (EC) has the potential to improve women's reproductive
      health significantly. In Honduras, where nearly one-fourth of pregnancies are
      unplanned, the need for EC is substantial. To increase awareness of this option,
      nongovernmental organizations launched countrywide EC outreach activities in 2001
      03. We conducted pre- and postintervention cross-sectional surveys among a total
      of 2,693 family planning clinic clients to assess EC knowledge, attitudes, and
      practice at baseline and at two years postintroduction. EC awareness increased
      over time, but remained at just 20 percent at follow-up. Respondents generally
      demonstrated a positive attitude and low rates of concern about EC. Awareness of
      and willingness to use EC were strongly associated with age, educational status,
      and city of residence. Public-sector acceptance of the method is essential to
      increase awareness of and access to EC. This study is intended to fill an
      information gap regarding EC in Latin America and the Caribbean and to be useful
      in determining educational messages and target audiences for future awareness
      campaigns in Honduras.

PMID- 17002198
TI  - Over-the-counter access, changing WHO guidelines, and contraindicated oral
      contraceptive use in Mexico.
AB  - This study examines the prevalence of contraindications to the use of oral
      contraceptives in Mexico by sociodemographic characteristics and by whether this
      family planning method was obtained with or without a doctor's prescription.
      Using data on smoking behavior and blood-pressure measurements from the 2000
      Mexican National Health Survey, the authors found that, under the 1996 World
      Health Organization (WHO) medical eligibility guidelines, the prevalence of
      contraindications is low and that no significant differences in contraindications
      exist at any level between those who obtain oral contraceptives at clinics and
      those who obtain them at pharmacies. In 2000, however, WHO substantially revised
      its criteria regarding the level of hypertension that would constitute a
      contraindication for oral contraceptive use. Applying the new guidelines, the
      authors found that 10 percent of pill users younger than 35 and 33 percent aged
      35 and older have health conditions that are either relative or absolute
      (Category 3 or 4) contraindications. The relevance of these findings to the
      larger debate concerning screening and over-the-counter access to oral
      contraceptives is discussed.

PMID- 17002199
TI  - Peru 2004-05: results from the Demographic and Family Health Survey.

PMID- 17002200
TI  - Tanzania 2004-05: results from the Demographic and Health Survey.

PMID- 17002201
TI  - [Studies on bacterial motility and chemosensory transduction].

PMID- 17002202
TI  - [Analysis of the factors involved in cell wall biosynthesis in Staphylococcus
      aureus].

PMID- 17002203
TI  - [Genome sequence of an invasive M3 strain of Streptococcus pyogenes].

PMID- 17002204
TI  - [Topology of bacterial cells focused on polar-localized proteins].

PMID- 17002205
TI  - [Super-integrons: a new strategy for bacterial resistant gene capture].

PMID- 17002206
TI  - [Molecular mechanisms of persistent infection and adherence/entry to host cells
      with Mycobacterium tuberculosis for the development of a novel therapeutic and
      prophylactic intervention].

PMID- 17002207
TI  - All's fair in love and war.

PMID- 17002208
TI  - Is crime scene examination science, and does it matter anyway?
AB  - This short piece aims to assess the kind of data collected by Crime Scene
      Examiners (CSEs), and to discuss whether this collection constitutes a scientific
      process. It also seeks to examine the balance of roles performed by the CSE,
      between data gatherer and investigator. The piece also aims to conclude on
      whether a clearer understanding of the structure of data collected by CSEs might
      be of some practical use in developing a greater understanding of the
      architecture of knowledge that forensic science as a whole relies upon. As a
      piece of work it is unapologetically theoretical in its perspective, and seeks to
      prompt further discussion regarding the structure of scientific knowledge, and
      any relevance this might have to its application in a forensic context.
      Ultimately, it seeks the inclusion of the processes of data gathering performed
      largely by CSEs within the wider processes of forensic science.

PMID- 17002209
TI  - An extended likelihood ratio framework for interpreting evidence.
AB  - This paper reviews some current methods, the likelihood ratio-based approach and
      the full Bayesian approach for the interpretation of evidence and discusses
      previously identified shortcomings in them. It suggests an approach based on a
      compromise--based on an extended likelihood ratio--that may combine the merits of
      logic without overstepping acceptable bounds for the forensic scientist in the
      presentation of evidence. The approach is exposed formally and takes advantage of
      inferential networks called Bayesian networks.

PMID- 17002210
TI  - Survey of 1276 shoeprint impressions and development of an automatic shoeprint
      pattern matching facility.
AB  - 1276 shoeprints were collected at a scientific exhibition. Details regarding the
      age groups of the participants, style, size and manufacturer/brand of their shoes
      were recorded. The impressions were assigned to pattern groups showing that the
      most common pattern was present in only 1% of the population studied and most
      patterns were much less common. The impressions were digitized and a system
      developed for automatically sorting a database of images of outsole patterns in
      response to a reference image. The database images are ranked so that those from
      the same pattern group as the reference shoeprint are likely to be at the start
      of the list. A database of 486 complete shoeprint images belonging to 142 pattern
      groups was established with each group containing two or more examples. Tests of
      the system have shown that the first-ranked database image belongs to the same
      pattern group as the reference image 60% of the time and that a correct match
      appears within the first 5% of the ranked images 88% of the time. The system has
      translational and rotational invariance so that the spatial positioning of the
      reference shoeprint images does not have to correspond with the spatial
      positioning of the shoeprint images of the database. The performance of the
      system for matching partial shoeprints was also determined.

PMID- 17002211
TI  - Investigation into the temporal stability of aqueous standard solutions of
      psilocin and psilocybin using high performance liquid chromatography.
AB  - This paper reports an investigation into the temporal stability of aqueous
      solutions of psilocin and psilocybin reference drug standards over a period of
      fourteen days. This study was performed using high performance liquid
      chromatography utilising a (95:5% v/v) methanol: 10 mM ammonium formate, pH 3.5
      mobile phase and absorption detection at 269 nm. It was found that the exclusion
      of light significantly prolonged the useful life of standards, with aqueous
      solutions of both psilocin and psilocybin being stable over a period of seven
      days.

PMID- 17002212
TI  - The sensitivity and specificity of red-starch paper for the detection of saliva.
AB  - The detection of saliva in forensic casework is extremely important in many types
      of cases. This study describes a relatively sensitive method, based on a red dye
      bound to starch, for the detection of amylase. The sensitivity and specificity of
      the method has been examined by testing over 50 household products, various body
      fluids and five laboratory chemicals. This study demonstrated for the first time
      that positive results can be obtained from certain washing powders as well as
      other household products. As well as detecting amylase in saliva, positive Red
      Starch results were obtained from faeces and urine. The method was found to be
      suitable for the detection of mixtures of saliva and semen in conjunction with
      the Brentamine test for the detection of acid phosphatase.

PMID- 17002213
TI  - Sediment fingerprints: a forensic technique using quartz sand grains.
AB  - The analyses of 738 soil and sediment samples taken during the investigation of
      20 forensic cases are combined in a database for retrospective comparisons.
      Quartz sand grain surface textures are combined into grain types which are
      analysed at one of five orders of classification. This classification also
      provides frequency data on the number of grain types found in a sample, the
      individuality of the quartz grain type assemblages and quartz grain type ratios.
      The technique, developed primarily as an exclusion mechanism, suggests
      possibilities, in some circumstances, that significant interpretations can be
      achieved at different orders of classification. The technique provides excellent
      exclusionary results and, when combined with other independent lines of analysis,
      is a powerful tool in forensic interpretation because it uses quartz as its
      discriminatory mineral. The technique also highlights the potential for computer
      image recognition analysis.

PMID- 17002214
TI  - Innovation, productivity and the art of risk management.

PMID- 17002215
TI  - Eating, sleeping and rewarding: orexin receptors and their antagonists.
AB  - The orexin system plays a key role in the control of eating, sleeping and
      rewarding. This review summarizes the latest developments in the identification
      of orexin receptor antagonists. By using a selective orexin-1 receptor
      antagonist, SB-334867-A (GlaxoSnzithKline plc), the in vivo futctions of both the
      orexin-1 and orexin-2 receptors have been elucidated. This review also
      sunmmarizes the literature and current opinions up to May 2006 on the therapeutic
      utility of orexin receptor antagonists for the treatment of eating disorders,
      sleeping disorders and drug addiction.

PMID- 17002216
TI  - Galanin function in the central nervous system.
AB  - The peptide galanin is primarily expressed in the central nervous system (CNS)
      and it is active in a range of models of behavior. The identification of three
      galanin receptors, whose distribution of expression is distinct but overlapping,
      is evidence of the complexity of galanin's regulation of neuronal function. The
      majority of studies examining galanin have used broad methods to identify its
      function, employing nonselective peptide agonists and antagonists, or transgenic
      animal models. While these studies were informative, they provided limited
      insight to the specific receptors mediating the effects of galanin. The recent
      identification of potent, brain-permeable and selective galanin antagonists
      suggests it will be possible to gain greater insight into the function of each
      galanin receptor and their potential as therapeutic targets. This article reviews
      the roles identified for galanin in the CNS and how ligands of the galanin
      receptors, both peptidic and small-molecule, have been used to explore the
      behavioral models that characterize these roles.

PMID- 17002217
TI  - Recent advances in positive allosteric modulators of the AMPA receptor.
AB  - The alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propioic acid (AMPA) subtype of
      glutamate receptors mediate fast excitatory neurotransmission throughout the
      mammalian nervous system and participate in the forms of synaptic plasticity that
      are considered to underlie learning and memory. Positive allosteric modulators of
      these receptors are the subject of much investigation because of their emerging
      therapeutic potential for a range of psychiatric and neurological disorders such
      as schizophrenia and Alzheimer's disease. This review focuses on the most recent
      developments in preclinical and clinical research on novel classes of AMPA
      receptor positive modulators and highlights how the application of biostructural
      studies has increased our understanding of the biophysical effects produced by
      these drugs.

PMID- 17002218
TI  - Brain-derived neurotrophic factor mechanisms and function in adult synaptic
      plasticity: new insights and implications for therapy.
AB  - Synaptic plasticity, the fiundamental ability of synapses to undergo experience
      dependent changes in synaptic strength, is thought to underlie a range of long
      term adaptive responses of the central nervous system. The inability to generate
      or maintain appropriate changes in synaptic connectivity and neuronal circuitry
      is likely to impair cognitive futnction associated with many neurological and
      psychiatric disorders. The success of intervening therapeutic approaches will
      depend on the ability to target key component mechanisms in the complex process
      of synaptic plasticity. Brain-derived neurotrophic factor (BDNF) has emerged as a
      major regulator of synaptic plasticity and a key target in disorders such as
      major depression and Alzheimner's disease. This review discusses findings that
      link BDNF mechanisms in synaptic plasticity to disease mechanisms and possible
      future therapies.

PMID- 17002219
TI  - Ion channel modulators: new targets and new indications for old targets.
AB  - Over recent years, our ever-increasing knowledge of the physiological roles of
      specific ion channel subtypes has led to drug discovery efforts aimed at ion
      channels of unknown pharmacology. Two of these are the transient receptor
      potential (TRP) channel TRPV1 and the acid-sensing ion channel (ASIC) family.
      Drug discovery efforts focused on both of these targets have led to interesting
      outcomes related to species differences in the mechanism of action of TRPV1
      blockers and tissue differences in the physiological roles of the different ASIC
      subtypes. In addition to the pursuit of novel targets, recent evidence suggests
      that there are new indications for known channel subtypes and modulators,
      including pain management for sodium and T-type calcium channel blockers and
      urinary incontinence for K(ATP) openers.

PMID- 17002220
TI  - Inosine 5'-monophosphate dehydrogenase inhibitors for the treatment of autoimmune
      diseases.
AB  - Inosine 5'-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo
      biosynthesis of guanine nucleotides. Proliferation of T- and B-lymphocytes, a
      hallmark of many autoimnunne diseases, is heavily dependent on access to a large
      pool of guanine nucleotides. To support this activity IMPDH is upregulated. The
      clinical benefit observed with mnycophenolic acid, a potent IMPDH inhibitor, in a
      number of autoimmune diseases, including those associated with organ
      transplantation, rheumatoid arthritis, psoriasis, systemic lupus erythenmatosus
      and inflammatory bowel disease, has validated IMPDH as an immunosuppressive
      target, and triggered the search from the pharmaceutical industry for IMPDH
      inhibitors with best-in-class status. This review will highlight recent advances
      in the IMPDH field, with a focus on the discovery and development of non
      nucleoside IMPDH inhibitors.

PMID- 17002221
TI  - Hepatitis C virus NS3-4A protease inhibitors: countering viral subversion in
      vitro and showing promise in the clinic.
AB  - Hepatitis C virus (HCV) NS3.4A protease inhibitors have potential for treating
      chronic HCV disease. Robust antiviral effects have been reported for the three
      HCV NS3.4A inhibitors (BILN-2061 (ciluprevir), telaprevir (VX-950; Vertex
      Pharmaceuticals Inc./Janssen Pharnmaceutica NV/Mitsubishi Pharma Corp.) and SCH
      503034; Schering-Plough Research Institute) that have been studied in clinical
      trials to date in HCV-infected patients, and new inhibitor molecules continue to
      appear on the horizon. Herein, toe relate the remarkable progress of these drug
      candidates to recent evidence that suggests HCV might depend on NS3.4A protease
      to subvert multiple innate cellular defense mechanisms.

PMID- 17002222
TI  - Finger loop inhibitors of the HCV NS5B polymerase: discovery and prospects for
      new HCV therapy.
AB  - The hepatitis C virus (HCV) infects millions of people wzorldwzide and currently
      available therapies suffer from limited efficacy and severe side effects. This
      review describes the discovery of a novel class of non-nucleoside HCV non
      structural protein 5B (NS5B) polymerase inhibitors that inhibit the replication
      of viral RNA by binding to an allosteric site on the enzyme. Initial lead
      compounds based on a benzimidazole scaffold were optimized yielding novel indole
      derivatives with sub-micromolar activity in a cell-based replicon assay. X-ray
      crystallographic studies suggest that inhibitor binding interferes with the
      conformational movements of the protein that are necessary for enzyme activity.
      Finger loop inhibitors of HCV NS5B show potential for the development of novel
      anti-HCV therapeutics.

PMID- 17002223
TI  - Molecular and cellular mechanisms of apolipoprotein E4 neurotoxicity and
      potential therapeutic strategies.
AB  - Apolipoprotein (apo) E is a multifunctional protein that has central roles in
      lipid metabolism and neurobiology. It has three common isoforms (apoE2, apoE3 and
      apoE4) that have different effects on lipid and neuronal homneostasis. Unlike
      apoE3, tie most common isoform, apoE4 is a major risk factor for Alzheimer's
      disease (AD). Although the mechanisms underlying the actions of apoE4 in AD
      pathogenesis are still poorly understood, emerging data strongly suggest that
      apoE4, with its multiple cellular origins and multiple structural and biophysical
      properties, contributes to this disease by interacting with different factors
      through various pathways. Thus, multiple molecular and cellular mechanisms should
      be considered in developing anti-AD drugs that target apoE4.

PMID- 17002224
TI  - Reinforcement value and substitutability of sucrose and wheel running:
      implications for activity anorexia.
AB  - Choice between sucrose and wheel-running reinforcement was assessed in two
      experiments. In the first experiment, ten male Wistar rats were exposed to
      concurrent VI 30 s VI 30 s schedules of wheel-running and sucrose reinforcement.
      Sucrose concentration varied across concentrations of 2.5, 7.5, and 12.5%. As
      concentration increased, more behavior was allocated to sucrose and more
      reinforcements were obtained from that alternative. Allocation of behavior to
      wheel running decreased, but obtained wheel-running reinforcement did not change.
      Overall, the results suggested that food-deprived rats were sensitive to
      qualitative changes in food supply (sucrose concentration) while continuing to
      defend a level of physical activity (wheel running). In the second study, 15
      female Long Evans rats were exposed to concurrent variable ratio schedules of
      sucrose and wheel-running, wheel-running and wheel-running, and sucrose and
      sucrose reinforcement. For each pair of reinforcers, substitutability was
      assessed by the effect of income-compensated price changes on consumption of the
      two reinforcers. Results showed that, as expected, sucrose substituted for
      sucrose and wheel running substituted for wheel running. Wheel running, however,
      did not substitute for sucrose; but sucrose partially substituted for wheel
      running. We address the implications of the interrelationships of sucrose and
      wheel running for an understanding of activity anorexia.

PMID- 17002225
TI  - The effects of delayed reinforcement on variability and repetition of response
      sequences.
AB  - Four experiments examined the effects of delays to reinforcement on key peck
      sequences of pigeons maintained under multiple schedules of contingencies that
      produced variable or repetitive behavior. In Experiments 1, 2, and 4, in the
      repeat component only the sequence right-right-left-left earned food, and in the
      vary component four-response sequences different from the previous 10 earned
      food. Experiments 1 and 2 examined the effects of nonresetting and resetting
      delays to reinforcement, respectively. In Experiment 3, in the repeat component
      sequences had to be the same as one of the previous three, whereas in the vary
      component sequences had to be different from each of the previous three for food.
      Experiment 4 compared postreinforcer delays to prereinforcement delays. With
      immediate reinforcement sequences occurred at a similar rate in the two
      components, but were less variable in the repeat component. Delays to
      reinforcement decreased the rate of sequences similarly in both components, but
      affected variability differently. Variability increased in the repeat component,
      but was unaffected in the vary component. These effects occurred regardless of
      the manner in which the delay to reinforcement was programmed or the contingency
      used to generate repetitive behavior. Furthermore, the effects were unique to
      prereinforcement delays.

PMID- 17002226
TI  - Assessing unit-price related remifentanil choice in rhesus monkeys.
AB  - Given a commodity available at different prices, a unit-price account of choice
      predicts preference for the cheaper alternative. This experiment determined if
      rhesus monkeys preferred remifentanil (an ultra-short-acting micro-opioid
      agonist) delivered at a lower unit price over a higher-priced remifentanil
      alternative (Phases 1 and 3). Choice between equal-priced alternatives also was
      assessed (Phase 2). A discrete-trials procedure was arranged in which three
      monkeys chose between two remifentanil alternatives by responding on one of two
      levers. Different prices were arranged by manipulating drug dose (0.3 and 0.1
      microg/kg/injection) and/or the ratio requirement. Monkeys usually chose the
      larger-dose alternative even when it was more expensive. Only when unit prices
      were relatively high (e.g., large response requirements) did monkeys choose the
      cheaper (or equally priced) smaller-dose alternative. Employing larger doses (0.9
      and 0.3 microg/kg/injection) attenuated the larger-dose preference. The results
      demonstrate that choice was not determined simply by unit price. An alternative
      model that employs demand-function analysis to generate choice predictions is
      proposed.

PMID- 17002227
TI  - Disruption of responding maintained by conditioned reinforcement: alterations in
      response-conditioned-reinforcer relations.
AB  - An observing procedure was used to investigate the effects of alterations in
      response-conditioned-reinforcer relations on observing. Pigeons responded to
      produce schedule-correlated stimuli paired with the availability of food or
      extinction. The contingency between observing responses and conditioned
      reinforcement was altered in three experiments. In Experiment 1, after a
      contingency was established in baseline between the observing response and
      conditioned reinforcement, it was removed and the schedule-correlated stimuli
      were presented independently of responding according to a variable-time schedule.
      The variable-time schedule was constructed such that the rate of stimulus
      presentations was yoked from baseline. The removal of the observing contingency
      reliably reduced rates of observing. In Experiment 2, resetting delays to
      conditioned reinforcement were imposed between observing responses and the
      schedule-correlated stimuli they produced. Delay values of 0, 0.5, 1, 5, and 10 s
      were examined. Rates of observing varied inversely as a function of delay value.
      In Experiment 3, signaled and unsignaled resetting delays between observing
      responses and schedule-correlated stimuli were compared. Baseline rates of
      observing were decreased less by signaled delays than by unsignaled delays.
      Disruptions in response-conditioned-reinforcer relations produce similar
      behavioral effects to those found with primary reinforcement.

PMID- 17002228
TI  - Choice between single and multiple reinforcers in concurrent-chains schedules.
AB  - Pigeons responded on concurrent-chains schedules with equal variable-interval
      schedules as initial links. One terminal link delivered a single reinforcer after
      a fixed delay, and the other terminal link delivered either three or five
      reinforcers, each preceded by a fixed delay. Some conditions included a
      postreinforcer delay after the single reinforcer to equate the total durations of
      the two terminal links, but other conditions did not include such a
      postreinforcer delay. With short initial links, preference for the single
      reinforcer alternative decreased when a postreinforcer delay was present, but
      with long initial links, the postreinforcer delays had no significant effect on
      preference. In conditions with a postreinforcer delay, preference for the single
      reinforcer alternative frequently switched from above 50% to below 50% as the
      initial links were lengthened. This pattern of results was consistent with delay
      reduction theory (Squires & Fantino, 1971), but not with the contextual-choice
      model (Grace, 1994) or the hyperbolic value-added model (Mazur, 2001) as they
      have usually been applied. However, the hyperbolic value-added model could
      account for the results if its calculations were expanded to include reinforcers
      delivered in later terminal links. The implications of these findings for models
      of concurrent-chains performance are discussed.

PMID- 17002229
TI  - Pigeons' discrimination of Michotte's launching effect.
AB  - We trained four pigeons to discriminate a Michotte launching animation from three
      other animations using a go/no-go task. The pigeons received food for pecking at
      one of the animations, but not for pecking at the others. The four animations
      featured two types of interactions among objects: causal (direct launching) and
      noncausal (delayed, distal, and distal & delayed). Two pigeons were reinforced
      for pecking at the causal interaction, but not at the noncausal interactions; two
      other pigeons were reinforced for pecking at the distal & delayed interaction,
      but not at the other interactions. Both discriminations proved difficult for the
      pigeons to master; later tests suggested that the pigeons often learned the
      discriminations by attending to subtle stimulus properties other than the
      intended ones.

PMID- 17002230
TI  - Testing response-stimulus equivalence relations using differential responses as a
      sample.
AB  - This study tested the notion that an equivalence relation may include a response
      when differential responses are paired with stimuli presented during training.
      Eight normal adults learned three kinds of computer mouse movements as
      differential response topographies (R1, R2, and R3). Next, in matching-to-sample
      training, one of the response topographies was used to select a comparison
      stimulus B (B1, B2, or B3) conditionally upon presentation of sample stimulus A
      (A1, A2, or A3), and to select stimulus D (D1, D2, or D3) conditionally upon
      presentation of stimulus C (C1, C2, or C3). After two sample-comparison-response
      relations (ABR and CDR) were established, 18 sample-comparison relations were
      tested (BA, DC, RA, RB, RC, RD, AC, CA, AD, DA, BC, CB, BD, DB, AA, BB, CC, and
      DD). In the RA, RB, RC, and RD tests, the differential responses (R1, R2, and R3)
      were used as sample stimuli. All subjects made class-consistent comparison
      selections in the tests. This study provides evidence that responses may become
      members of an equivalence class.

PMID- 17002232
TI  - Basic concepts and issues: a primer on distribution and sales representative
      agreements in the medical device and durable medical equipment industries.
AB  - Counsel for a manufacturer of medical devices or durable medical equipment must
      have working knowledge of various legal disciplines to draft contracts with
      intermediaries (sales representatives and distributors) for the marketing and
      sale of the manufacturer's products. If the manufacturer wishes to sell its
      products abroad, counsel must become familiar with the laws and business
      practices of the target country, and methods of gaining access to the foreign
      market. This Article gives readers an overview of the applicable legal
      principles, under U.S. and foreign laws, in the areas of agency, contracts,
      healthcare regulation, consumer protection, intellectual property protection, and
      dealer protection. To aid counsel in drafting intermediary agreements, specific
      contractual terms and issues are explored in depth, including: appointment
      clauses, performance provisions, provisions concerning pricing and payment,
      protective clauses (shielding the manufacturer from liability), term and
      termination provisions, independent contractor clauses, export control clauses,
      recordkeeping and audit provisions, choice of law clauses, and dispute resolution
      clauses.

PMID- 17002231
TI  - Intertrial sources of stimulus control and delayed matching-to-sample performance
      in humans.
AB  - Two experiments compared delayed matching-to-sample (DMTS) accuracy under 2
      procedures in adults with mental retardation. In the trial-unique procedure,
      every trial in a session contained different stimuli. Thus, comparison stimuli
      that were correct on one trial were never incorrect on other trials in that
      session (or vice versa). In the 2-sample DMTS procedure, the same 2 comparison
      stimuli were presented on each trial, and their function changed quasi-randomly
      across trials conditional upon the sample stimulus. Across 2 experiments, 7 of 8
      subjects showed the highest overall accuracy under the trial-unique procedure,
      and no subject showed consistently higher accuracy under the 2-sample procedure.
      Negative, exponential decay functions fit to logit p values showed that this
      difference was due largely to the steeper delay-mediated decline in sample
      control for the 2-sample procedure. Stimulus-control analyses indicated that,
      under the 2-sample procedure, the selection of the comparison stimulus on Trial N
      was often controlled by the comparison stimulus selection on Trial N-1 rather
      than the Trial-N sample stimulus. This source of competing stimulus control is
      not present in trial-unique procedures. Experiment 2 manipulated intertrial
      interval duration. There was a small but consistent increase in accuracy as a
      function of intertrial interval duration under the 2-sample procedure, but not
      under the trial-unique procedure.

PMID- 17002233
TI  - Pharmaceutical marketing practices: balancing public health and law enforcement
      interests; moving beyond regulation-through-litigation.
AB  - Fraudulent or abusive sales and marketing practices by pharmaceutical companies
      can result in costly overutilization of products that are increasingly paid for
      by government healthcare programs and may result in adverse health and safety
      consequences to the patient-beneficiaries of those programs. Federal enforcement
      efforts in this area are largely modeled on those used to combat white-collar
      crime, with cases taking years to reach conclusion. This approach overlooks the
      impact on patients who receive unnecessary care or are denied access to
      appropriate care during the course of the investigation. Many states are
      beginning to regulate certain pharmaceutical sales and marketing practices, but
      state-by-state regulation ignores the importance of a uniform federal regulatory
      and enforcement approach in an area already occupied by federal law. This Article
      explores current federal and state efforts to limit overutilization, fraud, and
      abuse in the sale and marketing of prescription drugs, and illustrates the merits
      of an expanded role for the U.S. Food and Drug Administration (FDA) to regulate
      pharmaceutical sales and marketing practices. This approach borrows lessons
      learned from the FDA's efficient and effective regulatory and enforcement methods
      and maintains a careful balance between the interests of patient-beneficiaries,
      the government and industry.

PMID- 17002234
TI  - Advertising and promotion of medical devices.
AB  - Dr. Portnoy, a former senior clinical reviewer and manager for the FDA's Center
      for Devices and Radiological Health, provides guidance for determining acceptable
      practices for the claims, content, and appearance of advertising and promotional
      materials for medical devices. In the course of doing so, he discusses important
      regulatory and legal precedents, and provides examples of successful and
      problematic advertising and promotion strategies including those that resulted in
      FDA Warning Letters, enforcement activities, and in some cases, monetary and
      criminal penalties.

PMID- 17002235
TI  - Plasma concentrations of plant sterols: physiology and relationship with coronary
      heart disease.
AB  - Recently, it has been questioned whether elevated levels of circulating plant
      sterols increase the risk of coronary heart disease (CHD). To date, no definitive
      conclusions regarding such a relationship have been reached, nor have there been
      any studies summarizing the factors that contribute to the observed elevations in
      plant sterol concentrations in plasma. Thus, the purpose of this review is to
      systematically compare the plant sterol levels of subjects from the general
      population and to describe factors that contribute to the variations observed.
      The question of whether elevated plasma concentrations of plant sterols are
      associated with an increased risk of CHD was also assessed. Results indicate that
      the key factors accounting for variations in circulating plant sterol
      concentrations include: apolipoprotein E phenotypes, ATP-binding cassette
      transporter polymorphisms, use of statin drugs, presence of metabolic syndrome,
      dietary intake of plant sterols, gender, and analytical techniques used in the
      measurement of plant sterols in the plasma. An analysis of the studies examining
      the relationship between circulating levels of plant sterols and CHD risk in non
      sitosterolemic populations revealed no clear associations. Furthermore, it was
      shown that the above-mentioned factors play an important role in determining the
      levels of plant sterols in plasma. Since these factors may act as potential
      confounders, they must be controlled for before more solid conclusions can be
      reached.

PMID- 17002236
TI  - Reducing exposure to dioxins and related compounds through foods in the next
      generation.
AB  - Dioxins and related compounds are undesirable and unintended contaminants in the
      food supply, and dietary intake is the major route of exposure. Reducing dietary
      exposure to dioxins among the most vulnerable segments of the population (i.e.,
      pregnant women, infants, and young girls) is an effective strategy for reducing
      body burdens in future generations. Exposure to dioxins through foods can be
      minimized by selecting lower-fat versions of meats, poultry, and dairy products.
      Consuming all foods, including fatty fish, in recommended amounts is congruent
      with the goal of reducing dioxin intake exposure and maintaining good health.

PMID- 17002237
TI  - Vitamin D, aging, and the 2005 Dietary Guidelines for Americans.
AB  - The 2005 Dietary Guidelines for Americans recommend that older adults, people
      with dark skin, and those exposed to insufficient ultraviolet radiation (i.e.,
      sunlight) consume extra vitamin D from vitamin D-fortified foods and/or
      supplements. Individuals in these high-risk groups should consume 25 microg (1000
      IU) of vitamin D daily to maintain adequate blood concentrations of 25
      hydroxyvitamin D, the biomarker for vitamin D status. This review considers
      recommendations for vitamin D-rich foods and dietary supplements, as well as
      specific problems with self-prescribing sun exposure or artificial sources of
      ultraviolet radiation to meet the vitamin D recommendations for older people.

PMID- 17002238
TI  - Nutrition recommendations for the treatment and prevention of type 2 diabetes and
      the metabolic syndrome: an evidenced-based review.

PMID- 17002239
TI  - Regulation of the NMDA receptor: implications for neuropsychological development.
AB  - Recent work has shown that zinc is involved in the developmental regulation of
      neurotrophins and N-methyl-D-aspartate (NMDA) receptors, controlling use of
      glutamate as a neurotransmitter in the central nervous system (CNS). This is
      particularly important in the hippocampus, a region of the brain involved in
      learning and memory, and is an intriguing link to the role of zinc in
      neuropsychological development.

PMID- 17002240
TI  - Rape and sexual assault in psychiatric services is accepted and overlooked in a
      way that it never would in any other health setting.

PMID- 17002241
TI  - Out of sight.

PMID- 17002242
TI  - Dustbin diagnosis.

PMID- 17002243
TI  - Doing well by yourself.

PMID- 17002244
TI  - We are family.

PMID- 17002245
TI  - Connecting with children in care.

PMID- 17002247
TI  - The POVA list is a powerful tool to reduce abuse and misconduct.

PMID- 17002248
TI  - Welfare writes.

PMID- 17002249
TI  - This life. It was a big shock to realise that I nearly died. I won't take my
      health for granted any more.

PMID- 17002250
TI  - Asking the right questions.

PMID- 17002251
TI  - The voices don't like it.

PMID- 17002252
TI  - How to make a high impact. CSIP/NIMHE suggests 80 ways to improve service
      organisation and delivery.

PMID- 17002253
TI  - Women on the verge.

PMID- 17002254
TI  - Eleanor Dace rails against the commodification of human misery that passes for
      publishing.

PMID- 17002255
TI  - Cardiovascular disease strategies--directions after the human genome.

PMID- 17002256
TI  - Cardiovascular and renal developments: patent highlights January to June 2006.
AB  - Failure of the cardiovascular system is the main reason for mortality in
      industrialized countries, and is a major cause of chronic morbidity. As most of
      the numerous ways in which it can fail will manifest in the second half of life
      and are exacerbated by old age, this situation is not likely to change in the
      near future unless fundamentally new ways of treating or preventing hypertension,
      atherosclerosis, myocardial infarction, chronic heart failure and cardiac
      arrhythmia are found. This prospect keeps the pharmaceutical industry on a
      constant, intense search for new therapeutic targets, new drugs, and new ways to
      identify such targets and drugs, as well as monitoring patient responses to
      drugs. This summary highlights the most interesting developments seen in
      cardiovascular and renal patents (other than those claiming formulations or
      combinations of known drugs) published during the first half of 2006.

PMID- 17002257
TI  - Fundamentals of stem cell mobilization for the heart: prospects for treating
      heart disease.
AB  - Despite significant advances in the detection, prevention and treatment of
      congestive heart failure, it remains a leading cause of morbidity and mortality.
      Recent research has revealed the potential role of stem and progenitor cells in
      repairing and regenerating damaged myocardium. A number of pharmacological agents
      that mobilize these cells, including granulocyte-colony stimulating factor,
      statins and AMD-3100, are currently under investigation. This review summarizes
      the rationale behind using these agents, as well as describing the preclinical
      and clinical data supporting their efficacy.

PMID- 17002258
TI  - Cardiovascular effects of insulin sensitizers in diabetes.
AB  - Diabetic patients have a greatly increased relative risk of cardiovascular
      disease compared with patients without diabetes. Type 2 diabetes is caused by a
      combination of insulin resistance and impaired pancreatic secretion.
      Thiazolidinediones are a relatively new class of compounds for the treatment of
      type 2 diabetes mellitus that lower glucose levels by decreasing insulin
      resistance and glucose production by the liver. The cardiovascular benefits of
      thiazolidinediones include an increase in high-density lipoprotein, reduction in
      blood pressure, improvement in endothelial function, attenuation of markers of
      inflammation and reduction in albuminuria. Ongoing clinical trials are underway
      investigating the role of thiazolidinediones in the prevention of type 2 diabetes
      mellitus.

PMID- 17002259
TI  - Antibodies against oxidized low-density lipoprotein for the treatment of
      vulnerable plaques.
AB  - Inflammation caused by the accumulation of oxidized low-density lipoprotein
      (oxLDL) in the arterial wall is a key factor in the development of
      atherosclerosis. Accumulating evidence suggests that adaptive immune responses to
      oxLDL are of major importance in regulating the inflammatory response, and that
      humoral immunity largely has a protective effect in this process. This concept is
      supported by animal studies demonstrating that treatment with antibodies against
      oxLDL inhibits atherosclerosis. Human antibodies with high affinity and
      specificity for epitopes on oxLDL have been developed and are now, after
      appropriate safety testing and non-clinical toxicology, ready to be tested in
      humans. Patients that may benefit front antibody treatment are most likely to be
      high-risk individuals in which conventional treatments, including lipid-lowering
      statins, do not provide sufficient protection.

PMID- 17002260
TI  - Novel targets for the treatment of atherosclerosis.
AB  - Atherosclerosis remains the leading cause of death in developed countries and
      thus demands the development of safe therapeutic treatments. Novel risk factors,
      in addition to the traditional targets, are being assessed. The significance of
      inflammation in atherosclerotic plaque development has become indisputable. A
      large number of published studies support the fact that investigations of the
      inflammatory aspects of atherosclerosis will be the target for future
      development. The C-reactive protein in particular has drawn specific attention
      due to its role as an inflammatory marker of atherosclerosis. Novel targets for
      atherosclerotic intervention include inhibitors of cholesterol synthesis and
      absorption such as acyl-coenzyme A:cholesterol acyltransferase, acyl-coenzyme
      A:diacylglycerol acyltransferase and cholesteryl ester transfer protein
      inhibitors, potential novel antioxidants other than anti-inflammatory peroxisome
      proliferator activated receptor agonists, and apolipoprotein A-I mimetic
      peptides.

PMID- 17002261
TI  - Prospects for the development of novel anti-hyperlipidemic drugs.
AB  - Hyperlipidemia is a well-established risk factor for atherogenesis and
      cardiovascular disease. Statins have been the cornerstone of treatment for
      hyperlipidemia in recent years and have significantly contributed to the
      improvement of cardiovascular disease therapy. However, novel antihyperlipidemic
      agents that have been developed over the last decade possess the capacity to
      significantly reduce plasma lipoproteins. This review analyzes the
      pharmacological profile, effectiveness and safety of some promising drugs that
      are either already in clinical use (eg, ezetimibe and nicotinic acid) or under
      study (eg, acyl-CoA cholesterol acyltransferase inhibitors, cholesteryl ester
      transfer protein inhibitors and apolipoprotein A-IMilano).

PMID- 17002262
TI  - Drug evaluation: AMG-531 for the treatment of thrombocytopenias.
AB  - Amgen Inc is developing AMG-531, a peptibody that binds to the thrombopoietin
      receptor Mpl, for the potential treatment of immune thrombocytopenic purpura
      (ITP), chemotherapy-induced thrombocytopenia (CIT) and thrombocytopenia in
      myelodysplastic syndrome (MDS). Results of the US phase III trial in ITP are
      expected to be available in the second half of 2006, while a phase II trial in
      CIT is still underway. A Japanese phase II ITP study has been initiated, as has a
      phase II trial of MDS patients in the US and France.

PMID- 17002263
TI  - Drug evaluation: dronedarone, a novel non-iodinated anti-arrhythmic agent.
AB  - sanofi-aventis (formerly Sanofi-Synthelabo) is developing the oral class III anti
      arrhythmic agent dronedarone (Multaq) for the potential treatment and prevention
      of atrial fibrillation. In June 2005, sanofi-aventis submitted EU and US filings
      for atrial fibrillation. In October 2002, phase I trials for arrhythmia were
      reported to be ongoing in Japan.

PMID- 17002264
TI  - Drug evaluation: TAK-475--an oral inhibitor of squalene synthase for
      hyperlipidemia.
AB  - Takeda Pharmaceutical Co Ltd is developing TAK-475, a squalene synthetase
      inhibitor from a series of 4,1-benzoxazepine-3-acetic acid derivatives, for the
      potential oral treatment of hyperlipidemia. By March 2005, TAK-475 was undergoing
      phase III clinical trials in the US and Europe.

PMID- 17002265
TI  - The new WHO child growth charts.

PMID- 17002266
TI  - Safer car travel for children: the updated law.

PMID- 17002267
TI  - Emollient treatment for childhood eczema: involving children and parents.
AB  - Emollients are the mainstay of managing eczema but many children find them
      tedious and unpleasant to apply and they are thought to be under-prescribed and
      underused. This paper discusses the advantages of involving children and parents
      in treatment, and of giving them a choice of emollients and the chance to try out
      different ones at different times of day and at night. The author suggests
      practical ways of making emollient therapy more fun for children, for example by
      decorating tubs and other containers and applying creams to dolls and other
      suitable toys. Children, as well as adults, can become"expert patients" and any
      good ideas that they have can be shared with other children with eczema.
      Experience suggests that getting them more involved will improve concordance with
      treatment. It should be acknowledged that managing chronic eczema in children and
      young people is hard and it is important to praise and encourage the efforts that
      children and their parents are making.

PMID- 17002268
TI  - Lifestyle advice in preventing and treating type 2 diabetes.
AB  - Dietary advice from health professionals can play a significant part in
      preventing and managing type 2 diabetes. Overweight and obesity are strongly
      associated with this condition, and individually tailored advice on weight loss
      and maintaining an appropriate weight are useful, together with encouragement to
      take appropriate exercise. Current thinking about a healthy diet and lifestyle
      apply to people with type 2 diabetes, but those with this condition or who are at
      risk from it need to understand why diet and exercise are so important in their
      case. The article explores these issues, including specific aspects of diet such
      as carbohydrates and the glycaemic index.

PMID- 17002269
TI  - Helping bereaved children and parents.
AB  - When a child dies, or is bereaved of a parent or sibling, it changes a family for
      ever. Grief affects different family members in different ways and may prevent
      them from supporting one another effectively. An understanding and well informed
      approach from health professionals can help the family manage their grief and
      adjust to their new life without the person who has died.

PMID- 17002270
TI  - Understanding prebiotics in infant and childhood nutrition.
AB  - Prebiotics and probiotics are ingredients in the diet that strengthen beneficial
      microbes in the gut, especially bifidobacteria. This article discusses their
      effects on health and their use in infant formula and foods for children and
      adults. They may also have benefits for the elderly population, since
      bifidobacteria are known to decrease with old age.

PMID- 17002271
TI  - An independent modern voice for school nursing.

PMID- 17002272
TI  - Interactions of tryptophan, tryptophan peptides, and tryptophan alkyl esters at
      curved membrane interfaces.
AB  - Motivated by ongoing efforts to understand the mechanism of membrane protein
      crystallogenesis and transport in the lipidic cubic phase, the nature of the
      interaction between tryptophan and the bilayer/aqueous interface of the cubic
      phase has been investigated. The association was quantified by partitioning
      measurements that enabled the free energy of interaction to be determined.
      Temperature-dependent partitioning was used to parse the association free energy
      change into its enthalpic and entropic components. As has been observed with
      tryptophan derivatives interacting with glycerophospholipid bilayers in vesicles,
      tryptophan partitioning in the cubic phase is enthalpy driven. This is in
      contrast to partitioning into apolar solvents, which exhibits the classic
      hydrophobic effect whose hallmark is a favorable entropy change. These results
      with tryptophan are somewhat surprising given the simplicity, homogeneity, and
      curvature of the interface that prevails in the case of the cubic phase.
      Nevertheless, the interaction between tryptophan and the mesophase is very slight
      as revealed by its low partition coefficient. Additional evidence in support of
      the interaction was obtained by electronic absorption and fluorescence
      spectroscopy and fluorescence quenching. Partitioning proved insensitive to the
      lipid composition of the membrane, examined by doping with glycerophospholipids.
      However, the interaction could be manipulated in meaningful ways by the inclusion
      in the aqueous medium of salt, glycerol, or urea. The effects seen with
      tryptophan were amplified rationally when measurements were repeated using
      tryptophan alkyl esters and with tryptophan peptides of increasing length. These
      findings are interpreted in the context of the insertion, folding, and function
      of proteins in membranes.

PMID- 17002273
TI  - Inhibitors and inactivators of protein arginine deiminase 4: functional and
      structural characterization.
AB  - Protein arginine deiminase 4 (PAD4) is a transcriptional coregulator that
      catalyzes the calcium-dependent conversion of specific arginine residues in
      proteins to citrulline. Recently, we reported the synthesis and characterization
      of F-amidine, a potent and bioavailable irreversible inactivator of PAD4. Herein,
      we report our efforts to identify the steric and leaving group requirements for F
      amidine-induced PAD4 inactivation, the structure of the PAD4-F-amidine x calcium
      complex, and in vivo studies with N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L
      ornithine amide (Cl-amidine), a PAD4 inactivator with enhanced potency. The PAD4
      inactivators described herein will be useful pharmacological probes in
      characterizing the incompletely defined physiological role(s) of this enzyme. In
      addition, they represent potential lead compounds for the treatment of rheumatoid
      arthritis because a growing body of evidence supports a role for PAD4 in the
      onset and progression of this chronic autoimmune disorder.

PMID- 17002274
TI  - Characterization of the linker 2 region in human vimentin using site-directed
      spin labeling and electron paramagnetic resonance.
AB  - Site-directed spin labeling and electron paramagnetic resonance were used to
      probe residues 281-304 of human vimentin, a region that has been predicted to be
      a non-alpha-helical linker and the beginning of coiled-coil domain 2B. Though no
      direct test of linker structure has ever been made, this region has been
      hypothesized to be flexible with the polypeptide chains looping away from one
      another. EPR analysis of spin-labeled mutants indicates that (a) several residues
      reside in close proximity, suggesting that adjacent linker regions in a dimer run
      in parallel, and that (b) the polypeptide backbone is relatively rigid and
      inflexible in this region. However, this region does not show the characteristics
      of a coiled-coil as has been identified elsewhere in the molecule. Within this
      region, spectra from positions 283 and 291 are unique from all others thus far
      examined. These positions, predicted to be in a noncoiled-coil structure, display
      a significantly stronger interaction than the a-d contact positions of coiled
      coil regions. Analysis of the early stages of assembly by dialysis from 8 M urea
      and progressive thermal denaturation shows the close apposition and structural
      rigidity at residues 283 and 291 occurs very early in assembly and with a
      relatively sudden onset, well before coiled-coil formation in other parts of the
      molecule. These features are inconsistent with hypotheses that envision the
      linkers as flexible regions, or as looping away from one another, and raise the
      possibility that the linker may be the site at which dimer alignment and/or
      formation is initiated. Spin labels placed further downstream yield spectra
      suggesting that the first regular heptad of rod domain 2 begins at position 302.
      In conjunction with our previous characterization of region 305-336 and the
      solved structure of rod 2B from 328-405, the full extent of coiled-coil domain in
      rod 2B is now known, spanning from vimentin positions 302-405.

PMID- 17002275
TI  - Properties of the dark and signaling states of photoactive yellow protein probed
      by solution phase hydrogen/deuterium exchange and mass spectrometry.
AB  - The perturbations on conversion from the dark state to the signaling state in
      photoactive yellow protein have been determined by solution-phase
      hydrogen/deuterium exchange and mass spectrometry. Both the wild type and M100A
      mutant are used in this study, with the mutant providing over 90% conversion to
      the bleached state under steady-state illumination. We found perturbations in
      both the wild type and the mutant on illumination, consistent with a more
      flexible structure in the long-lived signaling (I2') state. In the case of the
      wild type, the conformational changes detected are mainly around the chromophore
      region. With the M100A mutant, differences in H/D exchange between the light and
      dark are more extensive as compared to wild type; not only are the chromophore
      surroundings affected, but significant increases in deuterium uptake in the N
      terminus and central beta-sheet are observed as well. On the basis of the data
      obtained from this study and previous findings, a sequence of events that leads
      to the perturbation of PYP following chromophore photoisomerization is proposed.

PMID- 17002276
TI  - Structural changes in the cytoplasmic domain of phospholamban by phosphorylation
      at Ser16: a molecular dynamics study.
AB  - Phospholamban is a 52-residue integral membrane protein that regulates the
      activity of the sarcoplasmic reticulum calcium pump in cardiac muscle. Its
      inhibitory action is relieved when phospholamban is phosphorylated at Ser16 by
      cAMP-dependent protein kinase. To computationally explore all possible
      conformations of the phosphorylated form, and thereby to understand the
      structural effects of phosphorylation, replica-exchange molecular dynamics (REMD)
      was applied to the cytoplasmic domain that includes Ser16. The simulations showed
      that (i) without phosphorylation, the region from Lys3 to Ser16 takes all alpha
      helical conformations; (ii) when phosphorylated, the alpha-helix is partially
      unwound in the C-terminal part (from Ser10 to Ala15) resulting in less extended
      conformations; (iii) the phosphate at Ser16 forms salt bridges with Arg9, Arg13,
      and/or Arg14; and (iv) the salt bridges with Arg13 and Arg14 distort the alpha
      helix and induce unwinding of the C-terminal part. We then applied conventional
      all-atom molecular dynamics simulations to the full-length phospholamban in the
      phospholipid bilayer. The results were consistent with those obtained with REMD
      simulations, suggesting that the transmembrane part of phospholamban and the
      lipid bilayer itself have only minor effects on the conformational changes in the
      cytoplasmic domain. The distortions caused by the salt bridges involving the
      phosphate at Ser16 readily explain the relief of the inhibitory effect of
      phospholamban by phosphorylation, as they will substantially reduce the
      population of all helical conformations, which are presumably required for the
      binding to the calcium pump. This will also be the mechanism for releasing the
      phosphorylated phospholamban from kinase.

PMID- 17002277
TI  - A photoaffinity analogue of discodermolide specifically labels a peptide in beta
      tubulin.
AB  - Discodermolide is a potentially important antitumor agent that stabilizes
      microtubules and blocks cells at the G2/M phase of the cell cycle in a manner
      similar to that of Taxol. Discodermolide also has unique properties that
      distinguish it from Taxol. In the present study, photoaffinity-labeled
      discodermolide analogues are used to investigate their binding site in tubulin.
      Three photoaffinity-labeled discodermolide analogues were synthesized, all of
      which promoted microtubule polymerization in the absence of GTP. The analogue,
      C19-[4-(4-(3)H-benzoyl-phenyl)-carbamate]-discodermolide (C19-[3H]BPC
      discodermolide), was selected for photolabeling studies because it had the
      highest extent of photoincorporation, approximately 1%, of the three radiolabeled
      discodermolide analogues explored. Although compared to discodermolide, C19-BPC
      discodermolide revealed no hypernucleation effect in the in vitro microtubule
      polymerization assay, it was more cytotoxic than discodermolide, and, like
      discodermolide, demonstrated synergism with Taxol. These results suggest that the
      hypernucleation effect of discodermolide is not involved in its cytotoxic
      activity. Similar to discodermolide, C19-BPC-discodermolide can effectively
      displace [3H]Taxol from microtubules, but Taxol cannot effectively displace C19
      [3H]BPC-discodermolide binding. Discodermolide can effectively displace C19
      [3H]BPC-discodermolide binding. Formic acid hydrolysis, immunoprecipitation
      experiments, and subtilisin digestion indicate that C19-BPC-discodermolide labels
      amino acid residues 305-433 in beta-tubulin. Further digestion with Asp-N and Arg
      C enzymes suggested that C19-BPC-discodermolide binds to amino acid residues, 355
      359, in beta-tubulin, which is in close proximity to the Taxol binding site.
      Molecular modeling guided by the above evidence led to a putative binding model
      for C19-BPC-discodermolide in tubulin.

PMID- 17002278
TI  - The NMR structure of an internal loop from 23S ribosomal RNA differs from its
      structure in crystals of 50s ribosomal subunits.
AB  - Internal loops play an important role in structure and folding of RNA and in
      recognition of RNA by other molecules such as proteins and ligands. An
      understanding of internal loops with propensities to form a particular structure
      will help predict RNA structure, recognition, and function. The structures of
      internal loops 5' 1009CUAAG1013 3'/3' 1168GAAGC1164 5' and 5' 998CUAAG1002 3'/3'
      1157GAAGC1153 5' from helix 40 of the large subunit rRNA in Deinococcus
      radiodurans and Escherichia coli, respectively, are phylogenetically conserved,
      suggesting functional relevance. The energetics and NMR solution structure of the
      loop were determined in the duplex 5' 1GGCUAAGAC9 3'/3' 18CCGAAGCUG10 5'. The
      internal loop forms a different structure in solution and in the crystal
      structures of the ribosomal subunits. In particular, the crystal structures have
      a bulged out adenine at the equivalent of position A15 and a reverse Hoogsteen UA
      pair (trans Watson-Crick/Hoogsteen UA) at the equivalent of U4 and A14, whereas
      the solution structure has a single hydrogen bond UA pair (cis Watson-Crick/sugar
      edge A15U4) between U4 and A15 and a sheared AA pair (trans Hoogsteen/sugar edge
      A14A5) between A5 and A14. There is cross-strand stacking between A6 and A14
      (A6/A14/A15 stacking pattern) in the NMR structure. All three structures have a
      sheared GA pair (trans Hoogsteen/sugar edge A6G13) at the equivalent of A6 and
      G13. The internal loop has contacts with ribosomal protein L20 and other parts of
      the RNA in the crystal structures. These contacts presumably provide the free
      energy to rearrange the base pairing in the loop. Evidently, molecular
      recognition of this internal loop involves induced fit binding, which could
      confer several advantages. The predicted thermodynamic stability of the loop
      agrees with the experimental value, even though the thermodynamic model assumes a
      Watson-Crick UA pair.

PMID- 17002279
TI  - The FliN-FliH interaction mediates localization of flagellar export ATPase FliI
      to the C ring complex.
AB  - FliH regulates the flagellar export ATPase FliI, preventing nonproductive ATP
      hydrolysis. FliH has been shown to stably associate with the C ring protein FliN.
      Analysis of this complex reveals that FliH is required for FliI localization to
      the C ring, and thus FliH not only inhibits FliI ATPase activity but also may act
      to target FliI to the basal body. Quantitative binding studies revealed a KD of
      110 nM for FliH binding to FliN. The KD for FliH binding of a FliN variant from a
      temperature-sensitive nonflagellate fliN point mutant was determined to be 270
      nM, suggesting a molecular explanation for its phenotype. Another variant FliN
      from a temperature-sensitive mutant with a different phenotype displayed binding
      with an intermediate affinity. Weak export activity in a fliN null mutant was
      greatly increased by overproduction of FliI, mimicking a previously observed FliH
      bypass effect and supporting the conclusion that FliN-FliH binding is important
      for localization of FliI to the C ring and thus the membrane-embedded export
      apparatus beyond. A model incorporating the present findings is presented.

PMID- 17002280
TI  - Defining lipid-interacting domains in the N-terminal region of apolipoprotein B.
AB  - Apolipoprotein B (apoB) is a nonexchangeable apolipoprotein that dictates the
      synthesis of chylomicrons and very low density lipoproteins. ApoB is the major
      protein in low density lipoprotein, also known as the "bad cholesterol" that is
      directly implicated in atherosclerosis. It has been suggested that the N-terminal
      domain of apoB plays a critical role in the formation of apoB-containing
      lipoproteins through the initial recruitment of phospholipids in the endoplasmic
      reticulum. However, very little is known about the mechanism of lipoprotein
      nucleation by apoB. Here we demonstrate that a strong phospholipid remodeling
      function is associated with the predicted alpha-helical and C-sheet domains in
      the N-terminal 17% of apoB (B17). Using dimyristoylphosphatidylcholine (DMPC) as
      a model lipid, these domains can convert multilamellar DMPC vesicles into
      discoidal-shaped particles. The nascent particles reconstituted from different
      apoB domains are distinctive and compositionally homogeneous. This phospholipid
      remodeling activity is also observed with egg phosphatidylcholine (egg PC) and is
      therefore not DMPC-dependent. Using kinetic analysis of the DMPC clearance assay,
      we show that the identified phospholipid binding sequences all map to the surface
      of the lipid binding pocket in the B17 model based on the homologous protein,
      lipovitellin. Since both B17 and microsomal triglyceride transfer protein (MTP),
      a critical chaperone during lipoprotein assembly, are homologous with
      lipovitellin, the identification of these phospholipid remodeling sequences in
      B17 provides important insights into the potential mechanism that initiates the
      assembly of apoB-containing lipoproteins.

PMID- 17002281
TI  - Effects of including an N-terminal insertion region and arginine-mimetic side
      chains in helical peptoid analogues of lung surfactant protein B.
AB  - Surfactant protein B (SP-B) is one of two helical, amphipathic proteins critical
      for the biophysical functioning of lung surfactant (LS) and hence is an important
      therapeutic protein. This small, complex 79mer has three internal disulfide bonds
      and homodimerizes via another disulfide bridge. A helical, amphipathic 25mer from
      the amino terminus (SP-B(1-25)) exhibits surface-active properties similar to
      those of full-length, synthetic SP-B. In previous work, we created helical, non
      natural mimics of SP-B(1-25) based on sequence-specific peptoid 17mers and
      demonstrated their biomimetic surface activity. Like SP-B(1-25), the peptoids
      were designed to adopt helical structures with cationic and nonpolar faces. Here,
      we compare the surface activities of six different helical peptoid analogues of
      SP-B(1-25) to investigate the importance of mimicking its N-terminal insertion
      domain as well as its two arginine residues, both thought to be important for the
      peptide's proper function. Although the peptoid analogues of SP-B(1-25) studied
      here share many similar features and all functionally mimic SP-B(1-25) to some
      degree, it is notable that small differences in their sequences and side chain
      chemistries lead to substantial differences in their observed interactions with a
      lipid film. A peptoid comprising a hydrophobic, helical insertion region with
      aromatic side chains shows more biomimetic surface activity than simpler
      peptoids, and even better activity, by comparison to natural LS, than SP-B(1-25).
      However, the substitution of lysine-like side chains for arginine-like side
      chains in the peptoid has little effect on biomimetic surface activity,
      indicating that interactions of the guanidino groups with lipids may not be
      critical for the function of these SP-B mimics.

PMID- 17002282
TI  - Coexisting stripe- and patch-shaped domains in giant unilamellar vesicles.
AB  - We report a new type of gel-liquid phase segregation in giant unilamellar
      vesicles (GUVs) of mixed lipids. Coexisting patch- and stripe-shaped gel domains
      in GUV bilayers composed of DOPC/DPPC or DLPC/DPPC are observed by confocal
      fluorescence microscopy. The lipids in stripe domains are shown to be tilted
      according to the DiIC18 fluorescence intensity dependence on the excitation
      polarization. The patch domains are found to be mainly composed of DPPC-d62
      according to the coherent anti-Stokes Raman scattering (CARS) images of DOPC/DPPC
      d62 bilayers. When cooling GUVs from above the miscibility temperature, the patch
      domains start to appear between the chain melting and the pretransition
      temperature of DPPC. In GUVs containing a high molar percentage of DPPC, the
      stripe domains form below the pretransition temperature. Our observations suggest
      that the patch and stripe domains are in the Pbeta' and Lbeta' gel phases,
      respectively. According to the thermoelastic properties of GUVs described by
      Needham and Evans [(1988) Biochemistry 27, 8261-8269], the Pbeta' and Lbeta'
      phases are formed at relatively low and high membrane tensions, respectively.
      GUVs with high DPPC percentage have high membrane surface tension and thus mainly
      exhibit Lbeta' domains, while GUVs with low DPPC percentage have low membrane
      surface tension and form Pbeta' domains accordingly. Adding negatively charged
      lipid to the lipid mixtures or applying an osmotic pressure to GUVs using sucrose
      solutions releases the surface tension and leads to the disappearance of the
      Lbeta' gel phase. The relationship between the observed domains in free-standing
      GUV bilayers and those in supported bilayers is discussed.

PMID- 17002283
TI  - Carboxyl terminus of severe acute respiratory syndrome coronavirus nucleocapsid
      protein: self-association analysis and nucleic acid binding characterization.
AB  - Coronavirus nucleocapsid (N) protein envelops the genomic RNA to form long
      helical nucleocapsid during virion assembly. Since N protein oligomerization is
      usually a crucial step in this process, characterization of such an
      oligomerization will help in the understanding of the possible mechanisms for
      nucleocapsid formation. The N protein of severe acute respiratory syndrome
      coronavirus (SARS-CoV) was recently discovered to self-associate by its carboxyl
      terminus. In this study, to further address the detailed understanding of the
      association feature of this C-terminus, its oligomerization was systematically
      investigated by size exclusion chromatography and chemical cross-linking assays.
      Our results clearly indicated that the C-terminal domain of SARS-CoV N protein
      could form not only dimers but also trimers, tetramers, and hexamers. Further
      analyses against six deletion mutants showed that residues 343-402 were necessary
      and sufficient for this C-terminus oligomerization. Although this segment
      contains many charged residues, differences in ionic strength have no effects on
      its oligomerization, indicating the absence of electrostatic force in SARS-CoV N
      protein C-terminus self-association. Gel shift assay results revealed that the
      SARS-CoV N protein C-terminus is also able to associate with nucleic acids and
      residues 363-382 are the responsible interaction partner, demonstrating that this
      fragment might involve genomic RNA binding sites. The fact that nucleic acid
      binding could promote the SARS-CoV N protein C-terminus to form high-order
      oligomers implies that the oligomeric SARS-CoV N protein probably combines with
      the viral genomic RNA in triggering long nucleocapsid formation.

PMID- 17002284
TI  - Assignment of the hydrogen-out-of-plane and -in-plane vibrations of the retinal
      chromophore in the K intermediate of pharaonis phoborhodopsin.
AB  - pharaonis phoborhodopsin (ppR; also called pharaonis sensory rhodopsin II, psR
      II) is a photoreceptor protein for negative phototaxis in Natronomonas pharaonis.
      Photoisomerization of the retinal chromophore from all-trans to 13-cis initiates
      conformational changes of the protein leading to activation of the cognate
      transducer protein (pHtrII). Elucidation of the initial photoreaction, formation
      of the K intermediate of ppR, is important for understanding the mechanism of
      storage of photon energy. We have reported the K minus ppR Fourier transform
      infrared (FTIR) spectra, including several vibrational bands of the retinal, the
      protein, and internal water molecules. It is interesting that more vibrational
      bands were observed in the hydrogen-out-of-plane (HOOP) region than for the light
      driven proton pump, bacteriorhodopsin. This result implied that the steric
      constraints on the retinal chromophore in the binding pocket of ppR are
      distributed more widely upon formation of the initial intermediate. In this
      study, we assigned the HOOP and hydrogen-in-plane vibrations by means of low
      temperature FTIR spectroscopy applied to ppR reconstituted with retinal
      deuterated at C7, C8, C10-C12, C14, and C15. As a result, the 966 (+)/971 (-) and
      958 (+)/961 (-) cm(-1) bands were assigned to the C7=C8 and C11=C12 Au HOOP
      modes, respectively, suggesting that the structural changes spread to the middle
      part of the retinal. The positive bands at 1001, 994, 987, and 979 cm(-1) were
      assigned to the C15-HOOP vibrations of the K intermediate, whose frequencies are
      similar to those of the K(L) intermediate of bacteriorhodopsin trapped at 135 K.
      Another positive band at 864 cm(-1) was assigned to the C14-HOOP vibration.
      Relatively many positive bands of hydrogen-in-plane vibrations supported the wide
      distribution of structural changes of the retinal as well. These results imply
      that the light energy was stored mainly in the distortions around the Schiff base
      region while some part of the energy was transferred to the distal part of the
      retinal.

PMID- 17002285
TI  - Vstx1, a modifier of Kv channel gating, localizes to the interfacial region of
      lipid bilayers.
AB  - VSTx1 is a tarantula venom toxin which binds to the archaebacterial voltage-gated
      potassium channel KvAP. VSTx1 is thought to access the voltage sensor domain of
      the channel via the lipid bilayer phase. In order to understand its mode of
      action and implications for the mechanism of channel activation, it is important
      to characterize the interactions of VSTx1 with lipid bilayers. Molecular dynamics
      (MD) simulations (for a total simulation time in excess of 0.2 micros) have been
      used to explore VSTx1 localization and interactions with zwitterionic (POPC) and
      with anionic (POPE/POPG) lipid bilayers. In particular, three series of MD
      simulations have been used to explore the net drift of VSTx1 relative to the
      center of a bilayer, starting from different locations of the toxin. The
      preferred location of the toxin is at the membrane/water interface. Although
      there are differences between POPC and POPE/POPG bilayers, in both cases the
      toxin forms favorable interactions at the interface, maximizing H-bonding to
      lipid headgroups and to water molecules while retaining interactions with the
      hydrophobic core of the bilayer. A 30 ns unrestrained simulation reveals dynamic
      partitioning of VSTx1 into the interface of a POPC bilayer. The preferential
      location of VSTx1 at the interface is discussed in the context of Kv channel
      gating models and provides support for a mode of action in which the toxin
      interacts with the Kv voltage sensor "paddle" formed by the S3 and S4 helices.

PMID- 17002286
TI  - Single alpha-domain constructs of the Na+/Ca2+ exchanger, NCLX, oligomerize to
      form a functional exchanger.
AB  - Spliced isoforms of the Na+/Ca2+ exchanger, NCLX, truncated at the alpha-repeat
      region have been identified. The activity and functional organization of such
      proteins are, however, poorly understood. In the present work, we have studied
      Na+/Ca2+ exchange mediated by single alpha-repeat constructs (alpha1 and alpha2)
      of NCLX. Sodium-dependent calcium transport was fluorescently detected in both
      the reversal and forward modes; calcium-dependent outward currents were also
      recorded using a whole cell patch configuration in HEK293 cells heterologously
      expressing either the alpha1 or alpha2 single-domain proteins. In contrast,
      calcium transport and reversal currents were not detected when cells were
      transfected with a vector or with an alpha2 mutant (alpha2-S273T). Thus, our data
      indicate that the single alpha-domain constructs mediate electrogenic Na+/Ca2+
      exchange. The alpha1 domain, but not the alpha2, exhibited partial sensitivity to
      the NCX inhibitor, KB-R7943, while Li+-dependent Ca2+ efflux was detected in
      cells expressing either the alpha1 or alpha2 construct. The functional
      organization of the single alpha-domain constructs was assessed using a dominant
      negative approach. Coexpression of the alpha1 or alpha2 constructs with the
      nonfunctional alpha2-S273T mutant had a synergistic inhibitory effect on Na+/Ca2+
      transport. Dose-dependence analysis of the inhibition of alpha2 construct
      activity by the alpha2-S273T mutant indicated that the functional unit is either
      a dimer or a trimer. Immunoprecipitation analysis indicated that the alpha2
      construct indeed interacts with the alpha2-S273T mutant. Taken together, our data
      indicate that although single alpha1 or alpha2 domain constructs are
      independently capable of Na+/Ca2+ exchange, oligomerization is required for their
      activity. Such organization may give rise to transport activity with distinct
      kinetic parameters and physiological roles.

PMID- 17002287
TI  - Redesign of Schistosoma mansoni NAD+ catabolizing enzyme: active site H103W
      mutation restores ADP-ribosyl cyclase activity.
AB  - Schistosoma mansoni NAD(P)+ catabolizing enzyme (SmNACE) is a new member of the
      ADP-ribosyl cyclase family. In contrast to all the other enzymes that are
      involved in the production of metabolites that elicit Ca2+ mobilization, SmNACE
      is virtually unable to transform NAD+ into the second messenger cyclic ADP-ribose
      (cADPR). Sequence alignments revealed that one of four conserved residues within
      the active site of these enzymes was replaced in SmNACE by a histidine (His103)
      instead of the highly conserved tryptophan. To find out whether the inability of
      SmNACE to catalyze the canonical ADP-ribosyl cyclase reaction is linked to this
      change, we have replaced His103 with a tryptophan. The H103W mutation in SmNACE
      was indeed found to restore ADP-ribosyl cyclase activity as cADPR amounts for 7%
      of the reaction products (i.e., a value larger than observed for other members of
      this family such as CD38). Introduction of a Trp103 residue provides some of the
      binding characteristics of mammalian ADP-ribosyl cyclases such as increased
      affinity for Cibacron blue and slow-binding inhibition by araF-NAD+. Homology
      modeling of wild-type and H103W mutant three-dimensional structures, and docking
      of substrates within the active sites, provides new insight into the catalytic
      mechanism of SmNACE. Both residue side chains share similar roles in the
      nicotinamide-ribose bond cleavage step leading to an E.ADP-ribosyl reaction
      intermediate. They diverge, however, in the evolution of this intermediate;
      His103 provides a more polar environment favoring the accessibility to water and
      hydrolysis leading to ADP-ribose at the expense of the intramolecular cyclization
      pathway resulting in cADPR.

PMID- 17002288
TI  - Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived
      glycosidase inhibitors.
AB  - Inhibition of glycosidases has great potential in the quest for highly potent and
      specific drugs to treat diseases such as diabetes, cancer, and viral infections.
      One of the most effective ways of designing such compounds is by mimicking the
      transition state. Here we describe the structural, kinetic, and thermodynamic
      dissection of binding of two glucoimidazole-derived compounds, which are among
      the most potent glycosidase inhibitors reported to date, with two family 1 beta
      glycosidases. Provocatively, while inclusion of the phenethyl moiety improves
      binding by a factor of 20-80-fold, this does not appear to result from better
      noncovalent interactions with the enzyme; instead, improved affinity may be
      derived from significantly better entropic contributions to binding displayed by
      the phenethyl-substituted imidazole compound.

PMID- 17002289
TI  - Pressure affects the structure and the dynamics of the D-galactose/D-glucose
      binding protein from Escherichia coli by perturbing the C-terminal domain of the
      protein.
AB  - The effect of the pressure on the structure and stability of the D-galactose/D
      glucose binding protein from Escherichia coli in the absence (GGBP) and in the
      presence (GGBP/Glc) of glucose was studied by Fourier transform infrared (FT-IR)
      spectroscopy and molecular dynamic (MD) simulations. FT-IR spectroscopy
      experiments showed that the protein beta-structures are more resistant than alpha
      helices structures to pressure value increases. In addition, the infrared data
      indicated that the binding of glucose stabilizes the protein structure against
      high pressure values, and the protein structure does not completely unfold up to
      pressure values close to 9000 bar. MD simulations allow a prediction of the most
      probable configuration of the protein, consistent with the increasing pressures
      on the two systems. The detailed analysis of the structures at molecular level
      confirms that, among secondary structures, alpha-helices are more sensitive than
      beta-structures to the destabilizing effect of high pressure and that glucose is
      able to preserve the structure of the protein in the complex. Moreover, the
      evidence of the different resistance of the two domains of this protein to high
      pressure is investigated and explained at a molecular level, indicating the
      importance of aromatic amino acid in protein stabilization.

PMID- 17002290
TI  - Effect of the inhibitor-resistant M69V substitution on the structures and
      populations of trans-enamine beta-lactamase intermediates.
AB  - The objective of this study was to determine the molecular factors that lead to
      beta-lactamase inhibitor resistance for the M69V variant in SHV-1 beta-lactamase.
      With mechanism-based inhibitors, the beta-lactamase forms an acyl-enzyme
      intermediate that consists of a trans-enamine derivative in the active site. This
      study focuses on these intermediates by introducing the E166A mutation that
      greatly retards deacylation. Thus, by comparing the properties of the E166A and
      M69V/E166A forms, we can explore the consequences of the resistance mutation at
      the level of the enamine acyl-enzyme forms. The reactions between the beta
      lactamase and the inhibitors tazobactam, sulbactam, and clavulanic acid are
      followed in single crystals of the enzymes by using a Raman microscope. The
      resulting Raman difference spectroscopic data provide detailed information about
      conformational events involving the enamine species as well as an estimate of
      their populations. The Raman difference spectra for each of the inhibitors in the
      E166A and M69V/E166A variants are very similar. In particular, detailed analysis
      of the main enamine Raman vibration near 1595 cm(-1) reveals that the structure
      and flexibility of the enamine fragments are essentially identical for each of
      the three inhibitors in E166A and in the M69V/E166A double mutant. This finding
      is in accord with the X-ray-derived structures, presented herein at 1.6-1.75 A
      resolution, of the trans-enamine intermediates formed by the three inhibitors in
      M69V/E166A. However, a comparison of Raman results for M69V/E166A and E166A shows
      that the M69V mutation results in a 40%, 25%, and negligible reductions in the
      enamine population when the beta-lactamase crystals are soaked in 5 mM
      tazobactam, clavulanic acid, and sulbactam solutions, respectively. The levels of
      enamine from tazobactam and clavulanic acid can be increased by increasing the
      concentrations of inhibitor in the mother liquor. Thus, the sensitivity of
      population levels to the inhibitor concentration in the mother liquor focuses
      attention on the properties of the encounter complex preceding acylation. It is
      proposed that for small ligands, such as tazobactam, sulbactam, and clavulanic
      acid, the positioning of the lactam ring in the active site in the correct
      orientation for acylation is only one of a number of poorly defined
      conformations. For tazobactam and clavulanic acid, the correctly oriented
      encounter complex is even less likely in the M69V variant, leading to a reduction
      in the level of inhibition of the enzyme via formation of the acyl-enzyme
      intermediate and the onset of resistance. Analysis of the X-ray structures of the
      three intermediates in M69V/E166A demonstrates that, compared to the structures
      for the E166A form, the oxyanion hole becomes smaller, providing one explanation
      for why acylation may be less efficient following the M69V substitution.

PMID- 17002291
TI  - Three-dimensional structure determination of a protein supercomplex that oxidizes
      methane to formaldehyde in Methylococcus capsulatus (Bath).
AB  - The oxidation of methane to methanol in methanotrophs is catalyzed by the enzyme
      methane monooxygenase (MMO). Two distinct forms of this enzyme exist, a soluble
      cytoplasmic MMO (sMMO) and a membrane-bound particulate form (pMMO). The active
      protein complex termed pMMO-C was purified recently from Methylococcus capsulatus
      (Bath). The complex consists of pMMO hydroxylase and an additional component pMMO
      R, which was proposed to be the reductase for the pMMO complex. Further study of
      this complex has led here to the proposal that the pMMO-R is in fact methanol
      dehydrogenase, the subsequent enzyme in the methane oxidation pathway by
      methanotrophs. We describe here the biochemical and biophysical characterization
      of a stable purified complex of pMMO hydroxylase (pMMO-H) with methanol
      dehydrogenase (MDH) and report the first three-dimensional (3D) structure,
      determined by cryoelectron microscopy and single particle analysis to
      approximately 16 A resolution. The 3D structure reported here provides the first
      insights into the supramolecular organization of pMMO with MDH. These studies of
      pMMO-MDH complexes have provided further understanding of the structural basis
      for the particular functions of the enzymes in this system which might also be of
      relevance to the complete process of methane oxidation by methanotrophs under
      high copper concentration in the environment.

PMID- 17002292
TI  - Spectroscopic and computational studies of reduction of the metal versus the
      tetrapyrrole ring of coenzyme F430 from methyl-coenzyme M reductase.
AB  - Methyl-coenzyme M reductase (MCR) catalyzes the final step in methane
      biosynthesis by methanogenic archaea and contains a redox-active nickel
      tetrahydrocorphin, coenzyme F430, at its active site. Spectroscopic and
      computational methods have been used to study a novel form of the coenzyme,
      called F330, which is obtained by reducing F430 with sodium borohydride (NaBH4).
      F330 exhibits a prominent absorption peak at 330 nm, which is blue shifted by 100
      nm relative to F430. Mass spectrometric studies demonstrate that the tetrapyrrole
      ring in F330 has undergone reduction, on the basis of the incorporation of
      protium (or deuterium), upon treatment of F430 with NaBH4 (or NaBD4). One- and
      two-dimensional NMR studies show that the site of reduction is the exocyclic
      ketone group of the tetrahydrocorphin. Resonance Raman studies indicate that
      elimination of this pi-bond increases the overall pi-bond order in the
      conjugative framework. X-ray absorption, magnetic circular dichroism, and
      computational results show that F330 contains low-spin Ni(II). Thus, conversion
      of F430 to F330 reduces the hydrocorphin ring but not the metal. Conversely,
      reduction of F430 with Ti(III) citrate to generate F380 (corresponding to the
      active MCR(red1) state) reduces the Ni(II) to Ni(I) but does not reduce the
      tetrapyrrole ring system, which is consistent with other studies [Piskorski, R.,
      and Jaun, B. (2003) J. Am. Chem. Soc. 125, 13120-13125; Craft, J. L., et al.
      (2004) J. Biol. Inorg. Chem. 9, 77-89]. The distinct origins of the absorption
      band shifts associated with the formation of F330 and F380 are discussed within
      the framework of our computational results. These studies on the nature of the
      product(s) of reduction of F430 are of interest in the context of the mechanism
      of methane formation by MCR and in relation to the chemistry of hydroporphinoid
      systems in general. The spectroscopic and time-dependent DFT calculations add
      important insight into the electronic structure of the nickel hydrocorphinate in
      its Ni(II) and Ni(I) valence states.

PMID- 17002293
TI  - Putidaredoxin-to-cytochrome P450cam electron transfer: differences between the
      two reductive steps required for catalysis.
AB  - Cytochrome P450cam (P450cam) is the terminal monooxygenase in a three-component
      camphor-hydroxylating system from Pseudomonas putida. The reaction cycle requires
      two distinct electron transfer (ET) processes from the [2Fe-2S] containing
      putidaredoxin (Pdx) to P450cam. Even though the mechanism of interaction and ET
      between the two proteins has been under investigation for over 30 years, the
      second reductive step and the effector role of Pdx are not fully understood. We
      utilized mutagenesis, kinetic, and computer modeling approaches to better
      understand differences between the two Pdx-to-P450cam ET events. Our results
      indicate that interacting residues and the ET pathways in the complexes formed
      between reduced Pdx (Pdx(r)) and the ferric and ferrous dioxygen-bound forms of
      P450cam (oxy-P450cam) are different. Pdx Asp38 and Trp106 were found to be key
      players in both reductive steps. Compared to the wild-type Pdx, the D38A, W106A,
      and delta106 mutants exhibited considerably higher Kd values for ferric P450cam
      and retained ca. 20% of the first electron transferring ability. In contrast, the
      binding affinity of the mutants for oxy-P450cam was not substantially altered
      while the second ET rates were <1%. On the basis of the kinetic and modeling data
      we conclude that (i) P450cam-Pdx interaction is highly specific in part because
      it is guided/controlled by the redox state of both partners; (ii) there are
      alternative ET routes from Pdx(r) to ferric P450cam and a unique pathway to oxy
      P450cam involving Asp38; (iii) Pdx Trp106 is a key structural element that
      couples the second ET event to product formation possibly via its "push" effect
      on the heme-binding loop.

PMID- 17002294
TI  - Determinants of specificity of MDM2 for the activation domains of p53 and p65:
      proline27 disrupts the MDM2-binding motif of p53.
AB  - Transcriptional activation and repression via the transcription factors p53 and
      p65 are mediated by hydrophobic short linear motifs (FXX phi phi) in their
      activation domains (ADs). To understand the molecular basis for specificity in
      binding to disparate biological targets, a series of chimeric peptides was
      synthesized, with sequences derived from the ADs of p53, which binds both the
      general transcriptional machinery and the repressor protein MDM2, and p65, which
      is reported to bind the general transcriptional machinery but not MDM2. The FXX
      phi phi motifs of p53 and p65 differ by only two residues, whereas the flanking
      sequences have no sequence identity. The affinities of the chimeric peptides to
      MDM2(25-117) and hTAF(II)31(1-140) were determined. Specificity for binding MDM2
      via FXX phi phi motifs derives almost entirely from Trp23 of p53, with a 3.0 kcal
      mol(-1) loss of binding energy when Trp23 is changed to p65-derived Leu. The
      identity of the N-terminal flanking sequence did not significantly affect binding
      to MDM2. In contrast, replacement of the C-terminal sequence of p53 with that of
      p65 increased the affinity of the chimera for MDM2 by 1.1 kcal mol(-1), contrary
      to expectations. Replacement of the highly conserved residue Pro27 of p53 with
      Ser from p65 resulted in a 2.3 kcal mol(-1) improvement in binding to MDM2,
      generating a ligand (p53-P27S) (Kd = 4.7 nM) that exhibits the highest MDM2
      affinity observed for a genetically encodable ligand. The basis for the increased
      affinity of p53-P27S over p53 was examined by circular dichroism and nuclear
      magnetic resonance. Pro27 disrupts the recognition alpha-helix of p53, with p53
      P27S significantly more alpha-helical than p53.

PMID- 17002296
TI  - Structure of SAP18: a ubiquitin fold in histone deacetylase complex assembly.
AB  - Signal transduction pathways are frequently found to repress transcription of
      target genes in the absence of stimulation and, conversely, to upregulate
      transcription in the presence of a signal. Transcription factors are central in
      this dual regulatory mechanism and widely use a generalized mechanism to repress
      transcription through recruitment of a Sin3-histone deacetylase (HDAC) complex to
      their binding sites on DNA. The protein SAP18 (Sin3-associated polypeptide of 18
      kDa) has been shown to play a key role in gene-specific recruitment of the HDAC
      complex by a number of transcription factors including Gli, GAGA, and Bicoid. The
      solution structure of SAP18 reveals a ubiquitin-like fold with several large loop
      insertions relative to other family members. This fold supports the functional
      role of SAP18 as a protein-protein adapter module and provides insight for how
      SAP18 may bridge the Sin3-HDAC complex to transcription factors.

PMID- 17002295
TI  - Saccharomyces cerevisiae replication protein A binds to single-stranded DNA in
      multiple salt-dependent modes.
AB  - We have examined the single-stranded DNA (ssDNA) binding properties of the
      Saccharomyces cerevisiae replication protein A (scRPA) using fluorescence
      titrations, isothermal titration calorimetry, and sedimentation equilibrium to
      determine whether scRPA can bind to ssDNA in multiple binding modes. We measured
      the occluded site size for scRPA binding poly(dT), as well as the stoichiometry,
      equilibrium binding constants, and binding enthalpy of scRPA-(dT)L complexes as a
      function of the oligodeoxynucleotide length, L. Sedimentation equilibrium studies
      show that scRPA is a stable heterotrimer over the range of [NaCl] examined (0.02
      1.5 M). However, the occluded site size, n, undergoes a salt-dependent transition
      between values of n = 18-20 nucleotides at low [NaCl] and values of n = 26-28
      nucleotides at high [NaCl], with a transition midpoint near 0.36 M NaCl (25.0
      degrees C, pH 8.1). Measurements of the stoichiometry of scRPA-(dT)L complexes
      also show a [NaCl]-dependent change in stoichiometry consistent with the observed
      change in the occluded site size. Measurements of the deltaH(obsd) for scRPA
      binding to (dT)L at 1.5 M NaCl yield a contact site size of 28 nucleotides,
      similar to the occluded site size determined at this [NaCl]. Altogether, these
      data support a model in which scRPA can bind to ssDNA in at least two binding
      modes, a low site size mode (n = 18 +/- 1 nucleotides), stabilized at low [NaCl],
      in which only three of its oligonucleotide/oligosaccharide binding folds (OB
      folds) are used, and a higher site size mode (n = 27 +/- 1 nucleotides),
      stabilized at higher [NaCl], which uses four of its OB-folds. No evidence for
      highly cooperative binding of scRPA to ssDNA was found under any conditions
      examined. Thus, scRPA shows some behavior similar to that of the E. coli SSB
      homotetramer, which also shows binding mode transitions, but some significant
      differences also exist.

PMID- 17002297
TI  - Structural plasticity of peptidyl-prolyl isomerase sFkpA is a key to its
      chaperone function as revealed by solution NMR.
AB  - Intramolecular dynamics of periplasmic chaperone FkpA-deltaCT (sFkpA) and its
      complexes with partially structured substrates are studied by NMR in solution.
      The backbone amide 15N relaxation of sFkpA reveals flexibility in the relative
      orientation between the dimerization domain and two juxtaposed catalytic domains
      identified in the X-ray structure of sFkpA. This flexibility is attributed to the
      structural plasticity within the long alpha-helical arm (helix III) consisting of
      residues 84 and 91. Residual dipolar couplings (RDCs) indicate an absence of
      fixed orientation between the sFkpA domains. The substrate binding surface of
      sFkpA is defined on the X-ray structure by mapping of chemical shift
      perturbations introduced by complexation of sFkpA with its corresponding protein
      substrates: partially folded RNase A S-protein and reduced carboxymethylated
      bovine alpha-lactalbumin (RCM-la). A comparison of 15N relaxation of apo-sFkpA
      and its complex with RNase A S-protein indicates an increased rigidity within the
      long alpha-helix III and decreased interdomain mobility of the complex. We
      speculate that these dynamic properties may play a key role in the chaperone
      activity of sFkpA, since ability to bind different substrates potentially
      requires structural adaptations of the chaperone protein. We show that binding of
      sFkpA to RNase A S-protein greatly reduces the population of aggregated
      oligomeric species of RNase A S-protein. Finally, a molecular model, the so
      called "mother's arms" model, is proposed to illustrate the mechanism of
      chaperone activity by FkpA.

PMID- 17002298
TI  - The sequence-dependent unfolding pathway plays a critical role in the
      amyloidogenicity of transthyretin.
AB  - Human transthyretin (TTR) is an amyloidogenic protein whose aggregation is
      associated with several types of amyloid diseases. The following mechanism of TTR
      amyloid formation has been proposed. TTR tetramer at first dissociates into
      native monomers, which is the rate-limiting step in fibril formation. The
      monomeric species then partially unfold to form amyloidogenic intermediates that
      subsequently undergo a downhill self-assembly process. The amyloid deposit can be
      facilitated by disease-associated point mutations. However, only subtle
      structural differences were observed between the crystal structures of the wild
      type and the disease-associated variants. To investigate how single-point
      mutations influence the effective energy landscapes of TTR monomers, molecular
      dynamics (MD) simulations were performed on wild-type TTR and two pathogenic
      variants. Principal coordinate analysis on MD-generated ensembles has revealed
      multiple unfolding pathways for each protein. Amyloidogenic intermediates with
      the dislocated C strand-loop-D strand motif were observed only on the unfolding
      pathways of V30M and L55P variants and not for wild-type TTR. Our study suggests
      that the sequence-dependent unfolding pathway plays a crucial role in the
      amyloidogenicity of TTR. Analyses of side chain concerted motions indicate that
      pathogenic mutations on "edge strands" disrupt the delicate side chain correlated
      motions, which in turn may alter the sequence of unfolding events.

PMID- 17002299
TI  - Propagating structural perturbation inside bacteriorhodopsin: crystal structures
      of the M state and the D96A and T46V mutants.
AB  - The X-ray diffraction structure of the non-illuminated D96A bacteriorhodopsin
      mutant reveals structural changes as far away as 15 A from residue 96, at the
      retinal, Trp-182, Ala-215, and waters 501, 402, and 401. The Asp-to-Ala side
      chain replacement breaks its hydrogen bond with Thr-46, and the resulting
      separation of the cytoplasmic ends of helices B and C is communicated to the
      retinal region through a chain of covalent and hydrogen bonds. The unexpected
      long-range consequences of the D96A mutation include breaking the hydrogen bond
      between O of Ala-215 and water 501 and the formation of a new hydrogen bond
      between water molecules 401 and 402 in the extracellular region. Because in the
      T46V mutant a new water molecule appears at Asp-96 and its hydrogen-bond to Ile
      45 replaces Thr-46 as its link to helix B, the separation of helices B and C is
      smaller than that in D96A, and there are no atomic displacements elsewhere in the
      protein. Propagation of conformational changes along the chain between the
      retinal and Thr-46 had been observed earlier in the crystal structures of the
      D96N and E204Q mutants but in the trapped M state. Consistent with the
      perturbation of the retinal region in D96A, little change of the Thr-46 region
      occurs between the non-illuminated and M states of this mutant. It appears that a
      local perturbation can propagate along a track in both directions between the
      retinal and the Asp-96/Thr-46 pair, either from photoisomerization of the retinal
      in the wild-type protein in one case or from the D96A mutation in the other.

PMID- 17002300
TI  - Kinetic properties of a MNB/DYRK1A mutant suitable for the elucidation of
      biochemical pathways.
AB  - Minibrain kinase/dual-specificity tyrosine phosphorylation regulated kinase 1A
      (MNB/DYRK1A) is a proline/arginine-directed serine/threonine kinase implicated in
      the learning deficits of Down syndrome. Epigallocatechin-3-gallate (EGCG), the
      major tea polyphenolic compound, is a potent MNB/DYRK1A inhibitor. In this study,
      we investigated the mechanism of EGCG inhibition of MNB/DYRK1A using a
      combination of genetic and biochemical approaches. In the testing system using
      MNB/DYRK1A-promoted Gli 1-dependent transcription as the readout, NIH3T3 cells
      expressing EGCG resistant MNB/DYRK1A mutant R21 were found to acquire EGCG
      resistance for a wide range of drug concentrations. Mutant R21 harbors a single
      K465R substitution, which produces a 3-fold gain in the EGCG resistance in vitro.
      However, the gain in the EGCG resistance alone cannot fully interpret the
      effectiveness of mutant R21 in suppressing EGCG in cultured cells. Kinetic
      analysis suggests that EGCG functions as a noncompetitive inhibitor against ATP.
      Interestingly, the K465R mutation changes the mode of EGCG inhibition on
      MNB/DYRK1A so that it becomes a competitive inhibitor against ATP. This
      competitive mode of EGCG inhibition coupled with high intracellular ATP
      concentrations and an elevated EGCG resistance are likely to be the basis for the
      resistant property of mutant R21 in cultured cells. The K465R mutation apparently
      transforms the intramolecular interactions required for MNB/DYRK1A catalysis.
      This mutant would also be valuable for the elucidation of the mechanisms of
      MNB/DYRK1A-catalyzed reaction.

PMID- 17002301
TI  - Evidence for activation of tissue factor by an allosteric disulfide bond.
AB  - Tissue Factor (TF) is the mammalian plasma membrane cofactor responsible for
      initiation of blood coagulation. Binding of blood coagulation factor VIIa to TF
      activates the serine proteinase zymogens factors IX and X by limited proteolysis
      leading to the formation of a thrombin and fibrin meshwork that stabilizes the
      thrombus. TF on the plasma membrane of cells resides mostly in a cryptic
      configuration, which rapidly transforms into an active configuration in response
      to certain stimuli. The extracellular part of TF consists of two fibronectin type
      III domains. The disulfide bond in the membrane proximal domain (Cys186-Cys209)
      is atypical for domains of this type in that it links adjacent strands in the
      same beta sheet, what we have called an allosteric bond. Ablation of the
      allosteric disulfide by mutating both cysteine residues severely impairs
      procoagulant activity. The thiol-alkylating agents N-ethylmaleimide and methyl
      methanethiolsulfonate block TF activation by ionomycin, while the thiol-oxidizing
      agent HgCl2 and dithiol cross-linkers promote activation. TF activation could not
      be explained by exposure of phosphatidylserine on the outer leaflet of the plasma
      membrane. Cryptic TF contained unpaired cysteine thiols that were depleted upon
      activation, and de-encryption was associated with a change in the conformation of
      the membrane-proximal domain. These findings imply that the Cys186-Cys209
      disulfide bond is reduced in the cryptic form of TF and that activation involves
      formation of the disulfide. It is likely that formation of this disulfide bond
      changes the conformation of the domain that facilitates productive binding of
      factors IX and X.

PMID- 17002302
TI  - Mechanistic investigations of the pseudouridine synthase RluA using RNA
      containing 5-fluorouridine.
AB  - The pseuoduridine synthases (psi synthases) isomerize uridine (U) to
      pseudouridine (psi) in RNA, and they fall into five families that share very
      limited sequence similarity but have the same overall fold and active-site
      architecture, including an essential Asp. The mechanism by which the psi
      synthases operate remains unknown, and mechanistic work has largely made use of
      RNA containing 5-fluorouridine (f5U) in place of U. The psi synthase TruA forms a
      covalent adduct with such RNA, and heat disruption of the adduct generates a
      hydrated product of f5U, which was reasonably concluded to result from the
      hydrolysis of an ester linkage between the essential Asp and f5U. In contrast,
      the psi synthase TruB, which is a member of a different family, does not form an
      adduct with f5U in RNA but catalyzes the rearrangement and hydration of the f5U,
      which labeling studies with [18O]water showed does not result from ester
      hydrolysis. To extend the line of mechanistic investigation to another family of
      psi synthases and an enzyme that makes an adduct with f5U in RNA, the behavior of
      RluA toward RNA containing f5U was examined. Stem-loop RNAs are shown to be good
      substrates for RluA. Heat denaturation of the adduct between RluA and RNA
      containing f5U produces a hydrated nucleoside product, and labeling studies show
      that hydration does not occur by ester hydrolysis. These results are interpreted
      in light of a consistent mechanistic scheme for the handling of f5U by psi
      synthases.

PMID- 17002303
TI  - Catalytic mechanism of Escherichia coli endonuclease VIII: roles of the
      intercalation loop and the zinc finger.
AB  - Endonuclease VIII (Nei) excises oxidatively damaged pyrimidines from DNA and
      shares structural and functional homology with formamidopyrimidine-DNA
      glycosylase. Although the structure of Escherichia coli Nei is solved [Zharkov et
      al. (2002) EMBO J. 21, 789-800], the functions of many of its amino acid residues
      involved in catalysis and substrate specificity are not known. We constructed a
      series of Nei mutants that interfere with eversion of the damaged base from the
      helix (QLY69-71AAA, DeltaQLY69-71) or perturb the conserved zinc finger (R171A,
      Q261A). Steady-state kinetics were measured with these mutant enzymes using
      substrates containing 5,6-dihydrouracil, two enantiomers of thymine glycol, 8-oxo
      7,8-dihydroguanine, and an abasic site positioned opposite each of the four
      canonical DNA bases. To some extent, all Nei mutants were deficient in processing
      damaged DNA, with mutations in the zinc finger generally having a more profound
      effect. Wild-type Nei showed prominent opposite-base specificity (G > C
      approximately = T > A) when the lesion was 5,6-dihydrouracil or cis-(5S,6R)
      thymine glycol but not for other lesions tested. Mutations in the Q69-Y71 loop
      eliminated this effect. Only wild-type Nei and Nei-Q261A mutants could be
      reductively cross-linked to damaged base-containing DNA. Experiments involving
      trapping with NaBH4 and the kinetics of DNA cleavage catalyzed by Nei-Q261A
      suggested that this mutant was deficient in regenerating free enzyme from the Nei
      DNA covalent complex formed during the reaction. We conclude that the opposite
      base specificity of Nei is primarily governed by residues in the Q69-Y71 loop and
      that both this loop and the zinc finger contribute significantly to the substrate
      specificity of Nei.

PMID- 17002304
TI  - The free energy of dissociation of oligomeric structure in phycocyanin is not
      linear with denaturant.
AB  - Using SEC HPLC and fluorescence anisotropy, absorption spectra were assigned to
      the specific oligomeric structures found with phycocyanin. The absorption spectra
      were used to quantify the population of each oligomeric form of the protein as a
      function of both urea concentration and temperature. Phycocyanin hexamers
      dissociate to trimers with equilibrium constants of 10(-6) to 10(-5). Phycocyanin
      trimers dissociate to monomers with equilibrium constants of 10(-15) to 10(-12).
      Both dissociation constants increase linearly with increasing urea concentration,
      and deltaG(o) values calculated from the equilibrium constants fit best with an
      exponential function. Our findings appear in contrast with the commonly used
      linear extrapolation model, deltaG(urea)(o) = deltaG(water)(o) + A[denaturant],
      in which a linear relationship exists between the free energy of protein
      unfolding or loss of quaternary structure and the denaturant concentration. Our
      data examines a smaller range of denaturant concentration than generally used,
      which might partially explain the inconsistency.

PMID- 17002305
TI  - Biogenesis and topology of the secretory Na+-K+-2Cl- cotransporter (NKCC1)
      studied in intact mammalian cells.
AB  - The "secretory" Na+-K+-2Cl- cotransporter (NKCC1) is a member of a small gene
      family with nine homologues in vertebrates. Of these, seven are known to be
      electroneutral chloride transporters. These transporters play a number of
      important physiological roles related to salt and water homeostasis and the
      control of intracellular chloride levels. Hydropathy analyses suggest that all of
      these transporters have a similar transmembrane topology consisting of relatively
      large intracellular N and C termini and a central hydrophobic domain containing
      12 membrane-spanning segments (MSSs). In recent experiments from our laboratory
      [Gerelsaikhan, T., and Turner, R. J. (2000) J. Biol. Chem. 275, 40471-40477], we
      employed an in vitro translation system to confirm that each of the putative MSSs
      of NKCC1 was capable of membrane integration in a manner consistent with a 12 MSS
      model. Here, we extend that work to the study of the biogenesis of NKCC1 in
      intact cells. We employ a truncation mutant approach that allows us to monitor
      this process quantitatively as successive MSSs are synthesized. While the results
      presented here confirm the 12 MSS model, they also indicate that the integration
      of NKCC1 into the membrane does not occur via a simple cotranslational process.
      In particular, we demonstrate that two MSSs, the second and sixth, require the
      presence of downstream sequence to efficiently integrate into the membrane.

PMID- 17002306
TI  - Tropomodulin binds two tropomyosins: a novel model for actin filament capping.
AB  - Tropomodulin, a tropomyosin-binding protein, caps the slow-growing (pointed) end
      of the actin filament regulating its dynamics. Tropomodulin, therefore, is
      important for determining cell morphology, cell movement, and muscle contraction.
      For the first time we show that one tropomodulin molecule simultaneously binds
      two tropomyosin molecules in a cooperative manner. On the basis of the
      tropomodulin solution structure and predicted secondary structure, we introduced
      a series of point mutations in regions important for tropomyosin binding and
      actin capping. Capping activity of these mutants was assayed by measuring actin
      polymerization using pyrene fluorescence. Using direct methods (circular
      dichroism and native gel electrophoresis) for detecting tropomodulin/tropomyosin
      binding, we localized the second tropomyosin-binding site to residues 109-144.
      Despite previous reports that the second binding site is for erythrocyte
      tropomyosin only, we found that both short nonmuscle and long muscle alpha
      tropomyosins bind there as well, though with different affinities. We propose a
      model for actin capping where one tropomodulin molecule can bind to two
      tropomyosin molecules at the pointed end.

PMID- 17002307
TI  - Aptamers targeted to an RNA hairpin show improved specificity compared to that of
      complementary oligonucleotides.
AB  - Aptamers interacting with RNA hairpins through loop-loop (so-called kissing)
      interactions have been described as an alternative to antisense oligomers for the
      recognition of RNA hairpins. R06, an RNA aptamer, was previously shown to form a
      kissing complex with the TAR (trans-activating responsive) hairpin of HIV-1 RNA
      (Duconge and Toulme (1999) RNA 5, 1605). We derived a chimeric locked nucleic
      acid (LNA)/DNA aptamer from R06 that retains the binding properties of the
      originally selected R06 aptamer. We demonstrated that this LNA/DNA aptamer
      competes with a peptide of the retroviral protein Tat for binding to TAR, even
      though the binding sites of the two ligands do not overlap each other. This
      suggests that upon binding, the aptamer TAR adopts a conformation that is no
      longer appropriate for Tat association. In contrast, a LNA/DNA antisense
      oligomer, which exhibits the same binding constant and displays the same base
      pairing potential as the chimeric aptamer, does not compete with Tat. Moreover,
      we showed that the LNA/DNA aptamer is a more specific TAR binder than the LNA/DNA
      antisense sequence. These results demonstrate the benefit of reading the three
      dimensional shape of an RNA target rather than its primary sequence for the
      design of highly specific oligonucleotides.

PMID- 17002308
TI  - Kosmotropic salt activation and substrate specificity of poliovirus protease 3C.
AB  - Picornaviruses produce a large polyprotein, which is cleaved by virally encoded
      cysteine peptidases, picornain-2A and -3C. Picornain-3C has characteristics of
      both the serine peptidase chymotrypsin and the cysteine peptidase papain in that
      the 3D structure resembles chymotrypsin, but its nucleophile is a cysteine SH
      rather than a serine OH group. We investigated the specificity of poliovirus
      picornain-3C (PV3C) protease and the influence of kosmotropic salts on catalytic
      activity, using FRET peptides related to a cleavable segment of the virus
      polyprotein. The peptidase activity of PV3C was found to be 100-fold higher in
      the presence of 1.5 M sodium citrate. This activation was anion-dependent,
      following the Hofmeister series citrate(3-) > SO4(2-) > HPO4(2-) > acetate- >
      HCO3(-) > Cl-. The activation appeared to be independent of substrate sequence
      and arose primarily from an increase in kcat. A shift to higher pH was also
      observed for the pK1 of the enzyme pH-activity profile. Experiments with the
      fluorescent probe ANS (1-anilino-8-naphthalene sulfonate) showed that the
      protease bound the dye in the presence of 1 M sodium citrate but not in its
      absence or in the presence of 1 M NaCl. Structural changes in PV3C protease were
      detected using circular dichroism and the thermodynamic data indicated a more
      organized active site in the presence of sodium citrate. PV3C protease was also
      activated in D2O, which was added to the activation by citrate. These effects
      seem to be related to nonspecific interactions between the solvent and the
      protein. Our data show that the catalytic efficiency of PV3C protease is
      modulated by the composition of the environment and that this modulation may play
      a role in the optimal processing of polyprotein for the virus assembly that
      occurs inside specific vesicles formed in poliovirus-infected cells.

PMID- 17002309
TI  - Hydrodynamic analysis of the human progesterone receptor A-isoform reveals that
      self-association occurs in the micromolar range.
AB  - Human progesterone receptors exist as two functionally distinct isoforms, an 83
      kDa A-receptor (PR-A) and a 99 kDa B-receptor (PR-B). The isoforms are identical
      except that PR-B has an additional 164 amino acids at its N-terminus. We have
      previously characterized the hydrodynamics and solution assembly energetics of PR
      B [Heneghan, A. F., et al. (2005) Biochemistry 44, 9528-9537], and here we
      present an analysis of PR-A. At micromolar concentrations of the receptor,
      sedimentation velocity studies demonstrate that PR-A undergoes a concentration
      dependent change in its sedimentation coefficient distribution, indicative of a
      self-associating system. Global analysis of data sets collected at multiple PR-A
      concentrations supports the presence of a hydrodynamically homogeneous 3.50 S
      monomer species in equilibrium with a 7.15 S dimer species. Sedimentation
      equilibrium analysis demonstrates that self-association can be rigorously
      described by a monomer-dimer assembly reaction and a dimerization free energy of 
      7.6 +/- 0.6 kcal/mol. Both the PR-A monomer and dimer are structurally
      asymmetric, although the extent of asymmetry is significantly decreased for the
      dimer, indicative of quaternary-induced hydrodynamic compaction. Limited
      proteolysis studies suggest that PR-A asymmetry arises from an ensemble of
      partially folded conformations within the N-terminal half of the molecule.
      Finally, comparison to our previous work on PR-B self-association energetics
      demonstrates that it dimerizes, under identical solution conditions, with an
      affinity at least 8-fold weaker than that of PR-A. Thus, residues unique to the B
      isoform destabilize receptor assembly energetics. Importantly, the physical and
      chemical driving forces underlying isoform-specific dimerization suggest that B
      unique amino acids modulate the energetics through an allosteric mechanism.

PMID- 17002310
TI  - Structure and cholesterol dynamics of caveolae/raft and nonraft plasma membrane
      domains.
AB  - Despite recognition that the plasma membrane (PM) is comprised of lipid raft
      domains that are key organizing sites of multiple signaling pathways and other
      cell functions, limited information is available regarding the structure and
      function in sterol dynamics of these microdomains. To begin to resolve these
      issues, MDCK membranes were subfractionated by three different techniques to
      produce (i) detergent-resistant membranes (DRM) and detergent-soluble membranes
      (DSM), (ii) nondetergent caveolae/rafts (NDCR), and (iii) nondetergent, affinity
      purified caveolae/rafts (ACR) and noncaveolae/nonrafts (NR). ACR exhibited the
      least cross contamination with other PM domains or intracellular membranes, in
      marked contrast to DRM that contained the highest level of cross contaminants.
      Spectral properties of dehydroergosterol (DHE), a naturally occurring fluorescent
      sterol, showed that ACR, NDCR, and NR did not contain crystalline sterol,
      consistent with the lack of crystalline sterol in PM of intact cells. In
      contrast, DRM contained significant levels of crystalline sterol. Fluorescence
      polarization of membrane probes showed that ACR were the least fluid and had the
      highest transbilayer fluidity gradient, the most liquid ordered phase, and the
      sterol dynamics most responsive to sterol carrier protein-2 (SCP-2). In contrast,
      DRM had structural properties similar to those of NR, anomalous (very fast)
      spontaneous sterol dynamics, and sterol dynamics that were unresponsive to SCP-2.
      Differences between the structural and functional properties of DRM and those of
      the nondetergent preparations (ACR and NDCR) were not due to the presence of
      detergent. A nondetergent, affinity-purified (ACR) lipid domain fraction isolated
      from MDCK cells for the first time revealed unique structural (noncrystalline
      sterol, liquid-ordered, high transbilayer fluidity gradient) and functional
      (cholesterol dynamics) properties of lipid rafts as compared to nonrafts (NR). In
      summary, this study showed membrane microdomains (rafts/caveolae) isolated by
      three different methodologies have unique structural, functional, and
      organizational characteristics.

PMID- 17002311
TI  - Identification of oxidized methionine sites in erythrocyte membrane protein by
      liquid chromatography/electrospray ionization mass spectrometry peptide mapping.
AB  - In this study, we used peptide mapping combined with liquid
      chromatography/electrospray ionization mass spectrometry (LC/ESI MS) to examine
      the methionine oxidation of band 3 of erythrocyte membrane protein. Initially, we
      identified the methionine sites oxidized by chloramine T (N-chloro-p
      toluenesulfoamide), a hydrophilic reagent. There were three oxidized methionines
      (Met 559, Met 741, and Met 909) in band 3, and these methionines were located in
      a hydrophilic region determined by previous topological studies of band 3. In
      addition, we found that C12E8, a polyoxyethylene detergent, leads to the
      oxidation of methionines in a transmembrane segment in band 3, and this oxidation
      occurs in a C12E8 preincubation time-dependent manner. In a previous study, it
      was found that peroxides accumulate in a polyoxyethylene detergent. Thus, our
      method enabled the direct and quantitative detection of protein damage due to
      detergent peroxides. Furthermore, we examined methionine oxidation in the
      presence of 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) or diethyl
      pyrocarbonate (DEPC), which induced either an outward or an inward conformation
      in band 3, respectively. Our results indicated that the location of Met 741 was
      associated with the band 3 conformation induced by band 3-mediated anion
      transport. In conclusion, we found that methionine oxidation can be applied to
      examine membrane protein structures as follows: (1) for topological studies of
      membrane proteins, (2) for assessing the quality of proteins in detergent
      solubilization studies, and (3) for the detection of conformational changes in
      membrane proteins.

PMID- 17002312
TI  - Thermodynamics of phosphopeptide binding to the human peptidyl prolyl cis/trans
      isomerase Pin1.
AB  - Proteins containing phosphorylated Ser/Thr-Pro motifs play key roles in numerous
      regulatory processes in the cell. The peptidyl prolyl cis/trans isomerase Pin1
      specifically catalyzes the conformational transition of phosphorylated Ser/Thr
      Pro motifs. Here we report the direct analysis of the thermodynamic properties of
      the interaction of the PPIase Pin1 with its substrate-analogue inhibitor Ac-Phe-D
      Thr(PO3H2)-Pip-Nal-Gln-NH2 specifically targeted to the PPIase active site based
      on the combination of isothermal titration calorimetry and studies on inhibition
      of enzymatic activity of wt Pin1 and active site variants. Determination of the
      thermodynamic parameters revealed an enthalpically and entropically favored
      interaction characterized by binding enthalpy deltaH(ITC) of -6.3 +/- 0.1 kcal
      mol(-1) and a TdeltaS(ITC) of 4.1 +/- 0.1 kcal mol(-1). The resulting
      dissociation constant KD for binding of the peptidic inhibitor with 1.8 x 10(-8)
      M resembles the dissociation constant of a Pin1 substrate in the transition
      state, suggesting a transition state analogue conformation of the bound
      inhibitor. The strongly decreased affinity of Pin1 for ligand at increasing ionic
      strength implicates that the potential of bidentate binding of a substrate
      protein by the PPIase and the WW domain of Pin1 may be required to deploy
      improved efficiency and specificity of Pin1 under conditions of physiological
      ionic strength.

PMID- 17002313
TI  - Acid-base chemical mechanism of homocitrate synthase from Saccharomyces
      cerevisiae.
AB  - Homocitrate synthase (acetyl-coenzyme A:2-ketoglutarate C-transferase; E.C.
      2.3.3.14) catalyzes the condensation of AcCoA and alpha-ketoglutarate to give
      homocitrate and CoA. The enzyme was found to be a Zn-containing metalloenzyme
      using inductively coupled plasma mass spectrometry. Dead-end analogues of alpha
      ketoglutarate were used to obtain information on the topography of the alpha
      ketoglutarate binding site. The alpha-carboxylate and alpha-oxo groups of alpha
      ketoglutarate are required for optimum binding to coordinate to the active site
      Zn. Optimum positioning of the alpha-carboxylate, alpha-oxo, and gamma
      carboxylate of alpha-ketoglutarate is likely mimicked by the location in space of
      the 2-carboxylate, pyridine nitrogen, and 4 carboxylate of pyridine 2,4
      dicarboxylate. The pH dependence of the kinetic parameters was determined to
      obtain information on the chemical mechanism of homocitrate synthase. The V
      profile is bell shaped with slopes of 1 and -1, giving pKa values of 6.7 and 8.0,
      while V/K(AcCoA) exhibits a slope of 2 on the acidic side with an average pKa
      value of 6.6 and a slope of -2 on basic side of the profile with an average pKa
      value of 8.2. The V/K(alpha-Kg) pH-rate profile exhibits a single pKa of 6.9 on
      the acidic side and two on the basic side with an average value of 7.8. The pH
      dependence of the Ki for glyoxylate, a competitive inhibitor vs alpha
      ketoglutarate, gives a pKa of 7.1 for a group, required to be protonated for
      optimum binding. Data suggest a chemical mechanism for the enzyme in which alpha
      ketoglutarate first binds to the active site Zn via its alpha-carboxylate and
      alpha-oxo groups, followed by acetyl-CoA. A general base then accepts a proton
      from the methyl of acetyl-CoA, and a general acid protonates the carbonyl of
      alpha-ketoglutarate in the formation of homocitryl-CoA. The general acid then
      acts as a base in deprotonating Zn-OH2 in the hydrolysis of homocitryl-CoA to
      give homocitrate and CoA. A solvent deuterium kinetic isotope effect of 1 is
      measured for homocitrate synthase, while a small pH-independent primary kinetic
      deuterium isotope effect (approximately 1.3) is observed using deuterioacetyl
      CoA. Data suggest rate-limiting condensation to form the alkoxide of homocitryl
      CoA, followed by hydrolysis to give products.

PMID- 17002314
TI  - Evolution of new function in the GTP cyclohydrolase II proteins of Streptomyces
      coelicolor.
AB  - The genome sequence of Streptomyces coelicolor contains three open reading frames
      (sco1441, sco2687, and sco6655) that encode proteins with significant (>40%)
      amino acid identity to GTP cyclohydrolase II (GCH II), which catalyzes the
      committed step in the biosynthesis of riboflavin. The physiological significance
      of the redundancy of these proteins in S. coelicolor is not known. However, the
      gene contexts of the three proteins are different, suggesting that they may serve
      alternate biological niches. Each of the three proteins was overexpressed in
      Escherichia coli and characterized to determine if their functions are
      biologically overlapping. As purified, each protein contains 1 molar equiv of
      zinc/mol of protein and utilizes guanosine 5'-triphosphate (GTP) as substrate.
      Two of these proteins (SCO 1441 and SCO 2687) produce the canonical product of
      GCH II, 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (APy).
      Remarkably, however, one of the three proteins (SCO 6655) converts GTP to 2-amino
      5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate (FAPy), as shown by
      UV-visible spectrophotometry, mass spectrometry, and NMR. This activity has been
      reported for a GTP cyclohydrolase III protein from Methanocaldococcus jannaschii
      [Graham, D. E., Xu, H., and White, R. H. (2002) Biochemistry 41, 15074-15084],
      which has no amino acid sequence homology to SCO 6655. Comparison of the
      sequences of these proteins and mapping onto the structure of the E. coli GCH II
      protein [Ren, J., Kotaka, M., Lockyer, M., Lamb, H. K., Hawkins, A. R., and
      Stammers, D. K. (2005) J. Biol. Chem. 280, 36912-36919] allowed identification of
      a switch residue, Met120, which appears to be responsible for the altered fate of
      GTP observed with SCO 6655; a Tyr is found in the analogous position of all
      proteins that have been shown to catalyze the conversion of GTP to APy. The
      Met120Tyr variant of SCO 6655 acquires the ability to catalyze the conversion of
      GTP to APy, suggesting a role for Tyr120 in the late phase of the reaction. Our
      data are consistent with duplication of GCH II in S. coelicolor promoting
      evolution of a new function. The physiological role(s) of the gene clusters that
      house GCH II homologues will be discussed.

PMID- 17002315
TI  - Overall kinetic mechanism of saccharopine dehydrogenase from Saccharomyces
      cerevisiae.
AB  - Kinetic data have been measured for the histidine-tagged saccharopine
      dehydrogenase from Saccharomyces cerevisiae, suggesting the ordered addition of
      nicotinamide adenine dinucleotide (NAD) followed by saccharopine in the
      physiologic reaction direction. In the opposite direction, the reduced
      nicotinamide adenine dinucleotide (NADH) adds to the enzyme first, while there is
      no preference for the order of binding of alpha-ketoglutarate (alpha-Kg) and
      lysine. In the direction of saccharopine formation, data also suggest that, at
      high concentrations, lysine inhibits the reaction by binding to free enzyme. In
      addition, uncompetitive substrate inhibition by alpha-Kg and double inhibition by
      NAD and alpha-Kg suggest the existence of an abortive E:NAD:alpha-Kg complex.
      Product inhibition by saccharopine is uncompetitive versus NADH, suggesting a
      practical irreversibility of the reaction at pH 7.0 in agreement with the overall
      K(eq). Saccharopine is noncompetitive versus lysine or alpha-Kg, suggesting the
      existence of both E:NADH:saccharopine and E:NAD:saccharopine complexes. NAD is
      competitive versus NADH, and noncompetitive versus lysine and alpha-Kg,
      indicating the combination of the dinucleotides with free enzyme. Dead-end
      inhibition studies are also consistent with the random addition of alpha-Kg and
      lysine. Leucine and oxalylglycine serve as lysine and alpha-Kg dead-end
      analogues, respectively, and are uncompetitive against NADH and noncompetitive
      against alpha-Kg and lysine, respectively. Oxaloacetate (OAA), pyruvate, and
      glutarate behave as dead-end analogues of lysine, which suggests that the lysine
      binding site has a higher affinity for keto acid analogues than does the alpha-Kg
      site or that dicarboxylic acids have more than one binding mode on the enzyme. In
      addition, OAA and glutarate also bind to free enzyme as does lysine at high
      concentrations. Glutarate gives S-parabolic noncompetitive inhibition versus
      NADH, indicating the formation of a E:(glutarate)2 complex as a result of
      occupying both the lysine- and alpha-Kg-binding sites. Pyruvate, a slow
      alternative keto acid substrate, exhibits competitive inhibition versus both
      lysine and alpha-Kg, suggesting the combination to the E:NADH:alpha-Kg and
      E:NADH:lysine enzyme forms. The equilibrium constant for the reaction has been
      measured at pH 7.0 as 3.9 x 10(-7) M by monitoring the change in NADH upon the
      addition of the enzyme. The Haldane relationship is in very good agreement with
      the directly measured value.

PMID- 17002317
TI  - Repeat motions and backbone flexibility in designed proteins with different
      numbers of identical consensus tetratricopeptide repeats.
AB  - The tetratricopeptide repeat (TPR) is a 34-residue helix-turn-helix motif that
      occurs as three or more tandem repeats in a wide variety of proteins. We have
      determined the repeat motions and backbone fluctuations of proteins containing
      two or three consensus TPR repeats (CTPR2 and CPTR3, respectively) using 15N NMR
      relaxation measurements. Rotational diffusion tensors calculated from these data
      for each repeat within each TPR protein indicate that there is a high degree of
      motional correlation between different repeats in the same protein. This is
      consistent with the prevailing view that repeat proteins, such as CTPR2 and
      CTPR3, behave as single cooperatively folded domains. The internal motions of
      backbone NH groups were determined using the Lipari-Szabo model-free formalism.
      For most residues, there was a clear separation between the influence of internal
      motion and the influence of global rotational tumbling on the observed magnetic
      relaxation. The local internal motions are highly restricted in most of the
      helical elements, with slightly greater flexibility in the linker elements.
      Comparisons between CTPR2 and CTPR3 indicate that an addition of a TPR repeat to
      the C-terminus (before the solvation helix) of CTPR2 slightly reduces the
      flexibility of the preceding helix.

PMID- 17002320
TI  - Synthesis of CdSe/CdTe nanobarbells.
AB  - Synthesis of monodisperse samples of CdSe nanorods with CdTe tips is achieved
      using the mechanism of rod nucleated growth to form CdSe/CdTe nanobarbells. This
      synthesis produces a nanocrystal displaying "type-II" behavior with a morphology
      that is particularly well suited for internal exciton separation and carrier
      transport.

PMID- 17002318
TI  - The vault exterior shell is a dynamic structure that allows incorporation of
      vault-associated proteins into its interior.
AB  - Vaults are 13 million Da ribonucleoprotein particles with a highly conserved
      structure. Expression and assembly by multimerization of an estimated 96 copies
      of a single protein, termed the major vault protein (MVP), is sufficient to form
      the minimal structure and entire exterior shell of the barrel-shaped vault
      particle. Multiple copies of two additional proteins, VPARP and TEP1, and a small
      untranslated vault RNA are also associated with vaults. We used the Sf9 insect
      cell expression system to form MVP-only recombinant vaults and performed a series
      of protein-mixing experiments to test whether this particle shell is able to
      exclude exogenous proteins from interacting with the vault interior.
      Surprisingly, we found that VPARP and TEP1 are able to incorporate into vaults
      even after the formation of the MVP vault particle shell is complete.
      Electrospray molecular mobility analysis and spectroscopic studies of vault
      interacting proteins were used to confirm this result. Our results demonstrate
      that the protein shell of the recombinant vault particle is a dynamic structure
      and suggest a possible mechanism for in vivo assembly of vault-interacting
      proteins into preformed vaults. Finally, this study suggests that the vault
      interior may functionally interact with the cellular milieu.

PMID- 17002316
TI  - Translesion synthesis past tamoxifen-derived DNA adducts by human DNA polymerases
      eta and kappa.
AB  - The long-term treatment of tamoxifen (TAM), widely used for adjuvant chemotherapy
      and chemoprevention for breast cancer, increases a risk of developing endometrial
      cancer. A high frequency of K-ras mutations has been observed in the endometrium
      of women treated with TAM. Human DNA polymerase (pol) eta and pol kappa are
      highly expressed in the reproductive organs and are associated with translesion
      synthesis past bulky DNA adducts. To explore the miscoding properties of alpha
      (N2-deoxyguanosinyl)tamoxifen (dG-N2-TAM), a major TAM-DNA adduct, site
      specifically modified oligodeoxynucleotides containing a single diastereoisomer
      of trans or cis forms of dG-N2-TAM were prepared by phosphoramidite chemical
      procedure and used as templates. The primer extension reaction catalyzed by pol
      kappa deltaC, a truncated form of pol kappa, extended more efficiently past the
      adduct than that of pol eta by incorporating dCMP, a correct base, opposite the
      adduct. With pol eta, all diastereoisomers of dG-N2-TAM promoted small amounts of
      direct incorporation of dAMP and deletions. With pol kappa deltaC, dG-N2-TAM
      promoted small amounts of dTMP and/or dAMP incorporations and deletions. The
      miscoding properties varied depending on the diastereoisomer of dG-N2-TAM adducts
      and the DNA pol used. Steady-state kinetic studies were also performed using
      either the nonspecific sequence or the K-ras gene sequence containing a single dG
      N2-TAM at the second base of codon 12. With pol eta, the bypass frequency past
      the dA x dG-N2-TAM pair positioned in the K-ras sequence was only 2.3 times lower
      than that for the dC x dG-N2-TAM pair, indicating that dG-N2-TAM in the K-ras
      sequence has higher miscoding potential than that in the nonspecific sequence.
      However, with pol kappa deltaC, the bypass frequency past the dC x dG-N2-TAM pair
      was higher than that of the dT x dG-N2-TAM pair in both sequences. The properties
      of pol eta and pol kappa are consistent with the mutagenic events attributed to
      TAM-DNA adducts.

PMID- 17002321
TI  - A new class of mixed-valence systems with orbitally degenerate organic redox
      centers. Examples based on hexa-rhenium molecular prisms.
AB  - The ligand-centered mixed-valence (LCMV) properties of two supramolecular
      complexes are reported: triangular prisms of the form ([Re(CO)3]2X)3-mu,mu',mu' '
      [tPyTz]2, where X is 2,2'-bisbenzimidazolate (1) or a pair of benzylthiols (2),
      and tPyTz is tri-(4-pyridyl)-1,3,5-triazine. Cyclic voltammetry demonstrates that
      the redox-accessible bridging ligands, tPyTz, are reduced in sequential, one
      electron reactions. The singly reduced prisms, which represent an unusual type of
      mixed-valence compound in which the tPyTz ligands themselves are the redox
      centers, show intense, broad intervalance transfer (IT) bands in the NIR,
      consistent with highly coupled MV species. Electroabsorption (Stark spectroscopy)
      measurements reveal small dipole moment changes associated with intervalence
      excitation (|Deltamu12| = 0.30 +/- 0.02 eA for 1- and 0.48 +/- 0.02 eA for 2-),
      as well as noncollinear transition dipole moment (mu12) and dipole moment change
      vectors (zeta approximately 45 degrees ). DFT electronic structure calculations
      support this unusual result, along with a through-space electronic interaction
      mechanism. The neutral complexes (D3h symmetry) possess doubly degenerate, but
      spatially distinct, LUMO and LUMO+ orbitals. The orbital degeneracy of the tPyTz
      ligands is lifted in the MV forms, resulting in nonsymmetrical charge
      redistribution within the molecules upon on optical IT.

PMID- 17002322
TI  - A blind structure prediction of ice XIV.
AB  - Evidence points to several hydrogen ordered ice phases of ice XII that exhibit
      topologically distinct hydrogen networks from one another and which are formed
      under kinetically controlled conditions.

PMID- 17002323
TI  - Efficient and selective Al-catalyzed alcohol oxidation via Oppenauer chemistry.
AB  - A highly active and selective Al-based catalytic Oppenauer (O) oxidation is
      reported. Quantitative and selective oxidations of a variety of benzylic,
      propargylic, allylic, and aliphatic primary and secondary alcohols were achieved
      using nitrobenzaldehyde derivatives as the oxidant and simple aluminum compounds
      as precatalysts.

PMID- 17002324
TI  - RNA-templated semiconductor nanocrystals.
AB  - The use of a biomolecular RNA template for the synthesis of CdS semiconductor
      nanocrystals is described. Transfer RNA, with a well-defined three-dimensional
      structure, is used as a scaffold and ligand system in the aqueous synthesis of
      CdS. We have found that nanocrystal structures can be modulated by the structure
      of the templating tRNA. When possessing a folded three-dimensional structure,
      tRNA-templated synthesis yields a single product. If the same tRNA is rendered
      unstructured through the introduction of destabilizing mutations, a range of
      products are observed. The results reported indicate that biomolecules can be
      used to systematically engineer the structures and properties of semiconductor
      based materials, and that the synergy between the dimensions of nanostructures
      and biomolecules provides a means to tune the properties of materials with
      nanoscale precision.

PMID- 17002325
TI  - Protein assembly line components in prodigiosin biosynthesis: characterization of
      PigA,G,H,I,J.
AB  - The red streptomycete metabolite prodigiosin has a unique tripyrrolic structure
      with two of the three pyrrolyl moieties in tandem. Five enzymes, PigA,G,H,I, and
      J, are involved in dipyrrole (rings A and B) formation. We have heterologously
      expressed and purified from Escherichia coli these five enzymes. At first,
      pyrrole ring A is formed on the peptidyl carrier protein PigG by one of two
      possible ways: (i) by action of the adenylation domain PigI that transforms l
      proline into l-prolyl-AMP and by the flavoprotein dehydrogenase PigA responsible
      for the four-electron oxidation reaction; (ii) by loading with the pyrrolyl-2
      carboxyl-(S)-pantetheinyl moiety from synthetic pyrrolyl-CoA using the
      phosphopantetheinyl transferase Sfp. Subsequently, pyrrole ring B is constructed
      by PigH after the transfer of ring A to the ketosynthase of PigJ. PigH consists
      of three domains: two acyl carrier proteins (ACPs) and a seryltransferase (SerT).
      Using HPLC and nanospray-Fourier Transform Mass Spectrometry (nFTMS), we
      established that all three domains of PigH undergo post-translational
      modifications and gained insight into the machinery involved in 2,2-dipyrrole
      biosynthesis.

PMID- 17002326
TI  - Noncovalent control for bottom-up assembly of functional supramolecular wires.
AB  - Noncovalent bonds have been used to assemble stacks of pi-electron-rich moieties
      at a surface, generating a pathway for charge transport. The system is comprised
      of a tetrathiafulvalene (TTF) derivative incorporating two amide groups which
      fasten the relative orientations of the electroactive moieties in the
      supramolecular polymer that is formed at the surface of graphite in octanoic
      acid. Scanning tunneling microscopy (STM) combined with molecular mechanics
      calculations has been used to prove the structure of the wires, and theory,
      corroborated with STS experiments, predicts that they are promising
      superstructures for charge transport.

PMID- 17002327
TI  - 2,7-Diphenyl[1]benzothieno[3,2-b]benzothiophene, a new organic semiconductor for
      air-stable organic field-effect transistors with mobilities up to 2.0 cm2 V(-1)
      s(-1).
AB  - Vapor-deposited thin films of a newly developed sulfur-containing heteroarene,
      2,7-diphenyl[1]benzothieno[3,2-b][1]benzothiophene (DPh-BTBT), were used as an
      active layer of OFETs, which showed excellent FET characteristics in ambient
      conditions with mobilities of approximately 2.0 cm2 V-1 s-1 and Ion/Ioff of 107.

PMID- 17002328
TI  - Three-coordinate metal centers in extended transition metal oxides.
AB  - The n = 3 Ruddlesden-Popper phase Sr3LaFe1.5Co1.5O10+/-delta is capable of
      sustaining O contents as low as O7.5 with a mean metal oxidation state of +2 and
      three coordination at the central site in the trilayer of originally octahedral
      transition metal sites. The shortening of the axial bonds to the flanking
      octahedral layers stabilizes the low oxidation state and consequent unusual low
      coordination number of the Fe2+ and Co2+ cations within the extended structure.

PMID- 17002329
TI  - Room-temperature decay and light reactivation of high-Tc ferromagnetism in an
      oxide-diluted magnetic semiconductor.
AB  - We present a novel route for manipulation of the ferromagnetic order in Co-doped
      TiO2 using UV laser irradiation. The ferromagnetic order of the nanocrystal films
      decays with aging in air at room temperature, which can be reactivated and
      enhanced by UV irradiation, whereas the coercive force reduces with irradiation
      time. Photoinduced trapped electrons were suggested to induce the ferromagnetic
      order. We believe that light manipulation is a general method for tuning the
      magnetic properties of oxide-based diluted magnetic semiconductors, which can
      find practical applications in future integrated magneto-optical nanoelectronics.

PMID- 17002331
TI  - Divergence in the behavior of the charge density wave in RETe3 (RE = rare-earth
      element) with temperature and RE element.
AB  - Comparable changes in the volume of RETe3 materials caused by temperature and RE
      size have opposite trends to the incommensurate charge density wave modulation.
      This is unique behavior among all reported charge density wave materials.

PMID- 17002330
TI  - Sensing vase-to-kite switching of cavitands by sum-frequency vibrational
      spectroscopy.
AB  - Vibrational sum frequency generation setup for the study of Langmuir film of
      cavitands molecules deposited at the water surface.

PMID- 17002332
TI  - Gold(I) catalyzed isomerization of 5-en-2-yn-1-yl acetates: an efficient access
      to acetoxy bicyclo[3.1.0]hexenes and 2-cycloalken-1-ones.
AB  - The gold(I) catalyzed rearrangement of 5-en-2-yn-1-yl acetates into
      functionalized acetoxy bicyclo[3.1.0]hexenes is described. The mild reaction
      conditions employed allow the efficient and rapid synthesis of a variety of such
      bicyclic compounds via a sequence of two gold(I)-catalyzed isomerization steps.
      Acetoxy bicyclo[3.1.0]hexenes products can be further transformed to 2
      cycloalkenones by simple methanolysis.

PMID- 17002333
TI  - A 3.0 micros room temperature excited state lifetime of a bistridentate RuII
      polypyridine complex for rod-like molecular arrays.
AB  - A bistridentate RuII-polypyridine complex [Ru(bqp)2]2+ (bqp = 2,6-bis(8'
      quinolinyl)pyridine) has been prepared, which has a coordination geometry much
      closer to a perfect octahedron than the typical Ru(terpyridine)2-type complex.
      Thus, the complex displays a 3.0 mus lifetime of the lowest excited metal-to
      ligand charge transfer (3MLCT) state at room temperature. This is, to the best of
      our knowledge, the longest MLCT state lifetime reported for a RuII-polypyridyl
      complex at room temperature. The structure allows for the future construction of
      rod-like, isomer-free molecular arrays by substitution of donor and acceptor
      moieties on the central pyridine units. This makes it a promising photosensitizer
      for applications in molecular devices for artificial photosynthesis and molecular
      electronics.

PMID- 17002334
TI  - Monitoring DPA release from a single germinating Bacillus subtilis endospore via
      surface-enhanced Raman scattering microscopy.
AB  - A method for monitoring DPA release from a single germinating Bacillus subtilis
      endospore is reported. High S/N ratio SERS spectra were obtained with excitation
      power 3 mW at 647.1 nm and 1 min spectral collection times. The method is proof
      of-principle for the SERS detection limit at the single spore level. This
      represents a 100- to 1000-fold improvement over previously reported detection
      limits for SERS-based measurements of DPA in endospores.

PMID- 17002335
TI  - High resolution 1H detected 1H,13C correlation spectra in MAS solid-state NMR
      using deuterated proteins with selective 1H,2H isotopic labeling of methyl
      groups.
AB  - MAS solid-state NMR experiments applied to biological solids are still hampered
      by low sensitivity and resolution. In this work, we employ a deuteration scheme
      in which individual methyl groups are selectively protonated. This labeling
      scheme allows the acquisition of proton carbon correlation spectra with a
      resolution comparable to that in solution-state NMR experiments. We observe an
      increase in resolution by a factor of 10-15 compared to standard heteronuclear
      correlation experiments using PMLG for 1H,1H dipolar decoupling in the indirect
      dimension. At the same time, the full sensitivity of the proton-based experiment
      is retained. In comparison to the heteronuclear detected version of the
      experiment, a gain in sensitivity of a factor of approximately 4.7 is achieved.

PMID- 17002336
TI  - Exchange of an imido ligand in bis(imido) complexes of uranium.
AB  - Addition of B(C6H5)3.H2O to U(NtBu)2I2(THF)2 provides U(NtBu)(O)I2(THF)2, a
      complex with a trans arrangement of the oxo and imido ligands. A DFT study on the
      Ph3PO adduct, U(NtBu)(O)I2(Ph3PO)2, reveals that there are six bonding orbitals
      in the O=U=N interaction, much like the bis(imido) N=U=N interaction. However,
      the calculations suggest that the multiple bonding in the oxo imido complexes is
      less covalent than that in the bis(imido) analogues.

PMID- 17002337
TI  - Extending the series: synthesis and characterization of a dicationic N
      heterocyclic selenium carbene analogue.
AB  - The room-temperature reaction between the Dipp2DAB ligand, SnCl2, and SeCl4
      results in the quantitative formation of a dicationic N-heterocyclic "carbenoid".
      This represents the first example of a chalcogenium dication that mimics the
      ubiquitous Arduengo-type carbenes; however, the electronic structure is
      significantly different.

PMID- 17002338
TI  - Chemically selective sensing through layer-by-layer incorporation of
      biorecognition into thin film substrates for surface-enhanced resonance Raman
      scattering.
AB  - In this work, the fabrication, characterization, and application of avidin/Ag
      nanoparticle layer-by-layer (LbL) films as chemically selective substrates for
      surface-enhanced resonance Raman scattering (SERRS) is demonstrated. The
      biospecific interaction between avidin and the small molecule biotin, one of the
      strongest known to exist in nature, is exploited to preferentially capture
      biotinylated species from solution. This highly favored adsorption is shown to
      yield SERRS concentration enhancements and improved detection sensitivities of
      ca. 102 for commercially available and in situ prepared biotinylated species over
      their nontagged counterparts.

PMID- 17002339
TI  - Sequence-specific association in aqueous media by integrating hydrogen bonding
      and dynamic covalent interactions.
AB  - Oligoamide strands that associate in a sequence-specific fashion into hydrogen
      bonded duplexes in nonpolar solvents were converted into disulfide cross-linked
      duplexes in aqueous media. Thus, by incorporating trityl-protected thiol groups,
      which allows the reversible formation of disulfide bonds, into the oligoamide
      strands, only duplexes consisting of complementary hydrogen-bonding sequences
      were formed in aqueous solution as well as in methanol. The sequence-specific
      cross-linking of oligoamide strands was confirmed by MALDI-TOF, reverse-phase
      HPLC, and by isolating a cross-linked duplex. This study demonstrates that the
      sequence-specificity characteristic of multiply hydrogen-bonded systems can be
      extended into competitive media through the interplay of H-bonding and reversible
      covalent interactions, based on which a new class of molecular associating and
      ligating units that are compatible with both polar and nonpolar environments can
      be conveniently obtained.

PMID- 17002340
TI  - Antifungal activity from 14-helical beta-peptides.
AB  - We have discovered that short beta-peptides (9 or 10 residues) designed to adopt
      globally amphiphilic helical conformations display significant antifungal
      activity. The most promising beta-peptides cause little lysis of human red blood
      cells at concentrations that kill Candida albicans, a common human fungal
      pathogen. Since fungi are eukaryotes, discrimination between fungal and human
      cells is a significant finding. Our beta-peptides are active under assay
      conditions that mimic physiological ionic strength; in contrast, alpha-helix
      forming host-defense alpha-peptides are inactive against C. albicans under these
      conditions.

PMID- 17002341
TI  - TEM-induced structural evolution in amorphous Fe oxide nanoparticles.
AB  - Exposure to the high energy electron beam of a TEM changes the morphology of
      amorphous Fe oxide nanoparticles from solid spheres to hollow shells. Amorphous
      Fe oxide nanoparticles prepared via high-temperature methods using hexadecylamine
      and trioctylphosphine oxide surfactants were compared to crystalline gamma-Fe2O3
      particles of similar size. Both sets of particles are fully characterized via
      SQUID magnetometry, X-ray powder diffraction, BET surface analysis, EPR
      spectroscopy, high-resolution transmission electron microscopy (TEM), and
      electron energy loss spectroscopy (EELS). Time-resolved TEM images reveal that
      the amorphous Fe oxide particles evolve from solid spheres into hollow shells in
      <2 min, whereas crystalline gamma-Fe2O3 are unaffected by the electron beam. The
      resulting nanocrystalline Fe oxide shells bear striking resemblance to core-shell
      nanocrystals, but are a result of a morphology change attributed to restructuring
      of particle voids and defects induced by quasi-melting in the TEM. These results
      thus imply that caution is necessary when using TEM to analyze nanoparticle core
      shell and heterostructured nanoparticles.

PMID- 17002342
TI  - Palladium-catalyzed alkylation of sp2 and sp3 C-H bonds with methylboroxine and
      alkylboronic acids: two distinct C-H activation pathways.
AB  - Palladium-catalyzed alkylations of sp2 and sp3 C-H bonds with either
      methylboroxine or alkylboronic acids were developed. Ag2O or AgCO3 is used as a
      crucial oxidant and promoter for the transmetalation step. Ether, ester, alcohol,
      and alkene functional groups are tolerated. A new C-H activation pathway
      differing from the cyclometalation process is elucidated using methylboroxine as
      the coupling partner.

PMID- 17002343
TI  - Efficient H2 adsorption by nanopores of high-purity double-walled carbon
      nanotubes.
AB  - DWNT buckypaper adsorbed much more hydrogen than did a SWNT bundle. XRD
      measurements and GCMC simulation results suggested that the DWNT bundle is
      loosely packed into an hexagonal array with interstitial pores which can
      efficiently adsorb H2 molecules.

PMID- 17002344
TI  - Solid-state 139La and 15N NMR spectroscopy of lanthanum-containing metallocenes.
AB  - A preliminary set of solid-state 139La and 15N NMR data for lanthanum-containing
      metallocenes is presented, including (C5H5)3La, (C5Me4H)3La, [(C5Me5)2La]+[BPh4]
      , and 15N-enriched [(C5Me4H)2La(THF)]215N2. Broad 139La NMR spectra, with
      breadths ranging from 600 kHz to 2.5 MHz, were acquired with piecewise QCPMG
      techniques at 9.4 T. Simulations of the spectra reveal 139La quadrupolar coupling
      constants (CQ) between 44 and 105 MHz. In addition, the first NMR measurement of
      a nitrogen chemical shift (CS) tensor for dinitrogen bound side-on to a metal
      atom is reported for [(C5Me4H)2La(THF)]215N2. The 139La NMR parameters show
      remarkable sensitivity to changes in metallocene structure and can be interpreted
      in an intuitive manner. Preliminary RHF and DFT calculations of 139La electric
      field gradient (EFG) and nitrogen CS tensors are used to provide tensor
      orientations and to rationalize the origin of the NMR parameters in terms of
      molecular structure and symmetry. The sensitivity of 139La and 15N NMR tensor
      parameters to changes in structure and bonding should prove invaluable in future
      studies of noncrystalline and disordered systems.

PMID- 17002345
TI  - Inverted sapphyrin: a new family of doubly N-confused expanded porphyrins.
AB  - The synthesis of an inverted, methoxylated sapphyrin derivative is described.
      This system, wherein inversion of pyrrolic nitrogen atoms is configurationally
      enforced via the use of a 3,3'-bipyrrolic precursor, displays what is best
      described as "weak aromaticity" as judged from its spectroscopic features and
      supporting theoretical calculations.

PMID- 17002346
TI  - Porous carbon powders prepared by ultrasonic spray pyrolysis.
AB  - New, thermally robust meso- and macroporous carbon powders were prepared by
      ultrasonic spray pyrolysis (USP) of aqueous solutions using an inexpensive high
      frequency ultrasound generator from a household humidifier. We choose our
      molecular precursors rationally, so that the expected decomposition pathways
      produce only remnant carbon atoms. Specifically, our rational design criterion
      led to halo-organic carboxylate salts, whose pyrolysis yields well-defined carbon
      solids with a temporary template being generated in situ, simply an inorganic
      salt, which is easily dissolved during aqueous workup. The materials have been
      characterized by SEM, TEM, XRD, 13C NMR MAS, XPS, FTIR spectroscopy, and BET
      surface area measurements. Changing the alkali metal alters the morphology and
      pore structure of the final material, which can be explained in terms of the
      observed differences in the DSC and TGA of the various precursors. This
      preparatory method provides an extremely facile and versatile method for the
      generation of meso- and macroporous carbons.

PMID- 17002347
TI  - Facile Ar-CF3 bond formation at Pd. Strikingly different outcomes of reductive
      elimination from [(Ph3P)2Pd(CF3)Ph] and [(Xantphos)Pd(CF3)Ph].
AB  - Facile and highly selective perfluoroalkyl-aryl reductive elimination from a
      metal center (Pd) has been demonstrated for the first time. At temperatures as
      low as 50-80 degrees C, [(Xantphos)Pd(Ph)CF3] undergoes remarkably clean
      decomposition to produce CF3Ph in high yield and selectivity. In contrast,
      analogous trifluoromethylpalladium aryls stabilized by rigid cis-chelating
      ligands such as dppe are completely unreactive at temperatures up to 130-140
      degrees C. Decomposition of [(Ph3P)2Pd(Ph)CF3] in the presence of PhI in benzene
      at 60 degrees C does not produce PhCF3 but rather leads to [(Ph3P)2Pd(Ph)I] and
      [Ph4P]+[(Ph3P)Pd(CF3)3]- in a 2:1 ratio with high selectivity.

PMID- 17002349
TI  - Asymmetric synergy between chiral dienes and diphosphines in cationic Rh(I)
      catalyzed intramolecular [4 + 2] cycloaddition.
AB  - High enantioselective [4 + 2] cycloaddition can be achieved by cationic Rh
      complexes bearing not only chiral phosphine but also chiral diene. This is the
      first example of asymmetric synergy between chiral dienes and diphosphines.

PMID- 17002348
TI  - Stereoselective synthesis of functionalized pyrrolidines via a [3 + 2]-annulation
      of N-Ts-alpha-amino aldehydes and 1,3-Bis(silyl)propenes.
AB  - An efficient protocol for stereoselective synthesis of densely functionalized
      pyrrolidines by a [3 + 2]-annulation of N-Ts-alpha-amino aldehydes and 1,3
      bis(silyl)propenes is described.

PMID- 17002350
TI  - Generation of carbamoyl- and thiocarbamoyllithium synthons having a hydrogen(s)
      or an aryl group on the nitrogen and their trapping with carbonyl electrophiles.
AB  - Dimetalated amides 1 (Y = O) were generated as the synthons of carbamoyllithiums
      2 (Y = O) by the reaction of isocyanates with iBu2AlTenBu and a subsequent
      tellurium-lithium exchange reaction. A series of amide derivatives 3 (Y = O) were
      obtained by the trapping of dianion 1 with electrophiles. This transformation can
      be successfully applied to the generation and trapping of thiocarbamoyllithium
      synthons 1 (Y = S) as well as to the nucleophilic introduction of the parent
      carbamoyl moiety H2NC(O).

PMID- 17002351
TI  - Organocatalytic enantioselective conjugate additions to enones.
AB  - Conjugate addition reactions of a wide range of nucleophilic enol species with
      enones, catalyzed by a cinchona alkaloid derived thiourea organocatalyst, have
      been developed with attending good yields and high enantioselectivities under a
      mild reaction condition. The general method provides an efficient approach to the
      preparation of versatile building blocks possessing various functional groups.

PMID- 17002352
TI  - Total synthesis of (-)-himgaline.
AB  - The first total synthesis of (-)-himgaline and a highly enantioselective
      synthesis of its congener (-)-GB 13 are described. Decarboxylative aza-Michael
      reaction of the hexacyclic lactone precursor under acidic conditions, followed by
      basic workup, yielded (-)-GB 13 in 80% yield. Cyclization of (-)-GB 13 to
      oxohimgaline under acidic conditions, followed by internally coordinated sodium
      triacetoxyborohydride reduction, gave (-)-himgaline as the exclusive product.

PMID- 17002353
TI  - A concise total synthesis of DL-histrionicotoxin.
AB  - The synthesis of (+/-)-histrionicotoxin has been achieved in just nine steps
      using a two-directional synthesis strategy. Key reactions include a two
      directional cross-metathesis, a tandem oxime formation/Michael addition/1,4
      prototopic shift/[3 + 2]-cycloaddition cascade, a selective Z,Z-bisenyne
      formation, and a one-pot N-O and bischloroacetylene reduction.

PMID- 17002354
TI  - Enantioselective synthesis of gamma-hydroxyenones by chiral base-catalyzed
      Kornblum DeLaMare rearrangement.
AB  - A cinchona-alkaloid catalyzed asymmetric Kornblum DeLaMare rearrangement has been
      developed. Thus, enantioenriched 4-hydroxyenones are prepared from dienes by a
      two-step sequence involving photochemical dioxygenation and chiral base-catalyzed
      desymmetrization of the resulting endoperoxides.

PMID- 17002355
TI  - Asymmetric allylboration of ketones catalyzed by chiral diols.
AB  - Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration
      of ketones. The reaction requires 15 mol % of 3,3'-Br2-BINOL as the catalyst and
      allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in
      good yields (76-93%) and high enantiomeric ratios (95:5-99.5:0.5). High
      diastereoselectivities (dr >/= 98:2) and enantioselectivities (er >/= 98:2) are
      obtained in the reactions of acetophenone with crotyldiisopropoxyboranes.

PMID- 17002356
TI  - Organocatalytic transfer hydrogenation of cyclic enones.
AB  - The first enantioselective organocatalytic transfer hydrogenation of cyclic
      enones has been accomplished. The use of iminium catalysis has provided a new
      organocatalytic strategy for the enantioselective reduction of beta,beta
      substituted alpha,beta-unsaturated cycloalkenones, to generate beta-stereogenic
      cyclic ketones. The use of imidazolidinone 4 as the asymmetric catalyst has been
      found to mediate the hydrogenation of a large class of enone substrates with tert
      butyl Hantzsch ester serving as an inexpensive source of hydrogen. The capacity
      of catalyst 4 to enable enantioselective transfer hydrogenation of cycloalkenones
      has been extended to five-, six-, and seven-membered ring systems. The sense of
      asymmetric induction is in complete accord with the stereochemical model first
      reported in conjunction with the use of catalyst 4 for enantioselective ketone
      Diels-Alder reactions.

PMID- 17002357
TI  - Antibody nanoarrays with a pitch of approximately 20 nanometers.
AB  - We have developed a strategy for preparing antibody nanoarrays by DNA templating.
      In the resulting tetragonal antibody arrays, each spot is a similarly orientated,
      individual antibody molecule (IgG). The separation between two adjacent IgG
      molecules is only approximately 20 nm.

PMID- 17002358
TI  - The micellar shuttle: thermoreversible, intact transfer of block copolymer
      micelles between an ionic liquid and water.
AB  - Poly(1,2-butadiene-block-ethylene oxide) (PB-PEO) block copolymer micelles are
      found to partition reversibly between an ionic liquid 1-butyl-3-methylimidazolium
      hexafluorophosphate ([BMIM][PF6]) and water, thereby functioning as micellar
      shuttles controlled simply by temperature. The micelle size and structure are
      preserved during this reversible phase transfer. This phenomenon offers a simple
      means to transport chemicals back and forth between two immiscible phases.

PMID- 17002359
TI  - Synthesis and solution- and solid-state characterization of gold(I) rings with
      short Au...Au interactions. Spontaneous resolution of a gold(I) complex.
AB  - We report the synthesis and solution- and solid-state characterization of gold(I)
      rings with short 1,9-transannular Au...Au interactions. The 9- and 16-membered
      gold(I) rings were prepared by reacting 9,9-dimethyl-4,5-bis(diphenylphosphino)
      xanthene and (Me2S)AuCl in the presence of AgNO3 in the molar ratio of 1:0.5:1
      and 1:1:1, respectively. X-ray crystallographic measurements in conjunction with
      solution X-ray diffraction and NMR methods have been used to determine the
      structure of gold(I) rings, and we also gained insight into the dynamics. The
      nine-membered gold(I) ring is chiral, and the crystal contains only one of the
      two enantiomers, either right- or left-handed. To the best of our knowledge this
      represents the first example of crystallization-induced spontaneous resolution of
      a binuclear gold(I) cycle. The 16-membered ring with 1,9-transannular Au...Au
      interaction is in a figure-eight conformation.

PMID- 17002360
TI  - Faceting of nanocrystals during chemical transformation: from solid silver
      spheres to hollow gold octahedra.
AB  - We demonstrate that performing a replacement reaction on single crystalline Ag
      nanospheres of approximately 10 nm in diameter in an organic solvent produces
      hollow Au nanocrystals with an octahedral shape. Different from those Au shells
      made by starting with Ag particles about 1 order of magnitude larger, which
      largely reproduce that of the sacrificial Ag counterparts, the hollow
      nanocrystals obtained in this work show significant changes in the external
      morphology from the spherical Ag precursors. This evolution of a faceted external
      morphology during chemical transformation is made possible by the enhanced role
      of surface effects in our smaller nanocrystals. The competition between the Au
      atom deposition and Ag atom dissolution on various nanocrystal surfaces is
      believed to determine the final octahedral shape of the hollow Au nanocrystals.
      Simultaneous achievement of surface-mediated shape control and a hollow
      morphology in a one-pot, single-step synthetic procedure in this study promises
      an avenue to finer tuning of particle morphology, and thus physical properties
      such as surface plasmon resonance.

PMID- 17002361
TI  - Control over charge separation in phthalocyanine-anthraquinone conjugates as a
      function of the aggregation status.
AB  - We have prepared three isomeric donor-acceptor systems, in which two
      phthalocyanine (Pc) units have been attached to the 1-,5- (1a), 1-,8- (1b), or 2
      ,6- (1c) positions of a central anthraquinone (AQ) moiety, leading to packed (1b)
      or extended (1a and 1c) topologies. The electronic interactions between the donor
      and the acceptor in the ground state or in the excited states have been studied
      by different electrochemical and photophysical techniques. Due to the markedly
      different topologies, we have been able to modify these interactions at the
      intramolecular level and, by a proper choice of the solvent environment, at the
      intermolecular level within aggregates. In triad 1b, the ZnPc units are forced to
      pi-stack cofacially and out of the plane of the AQ ring. Consequently, this
      molecule shows strong inter-Pc interactions that give rise to intramolecular
      excitonic coupling but a relatively small electronic communication with the AQ
      acceptor through the vinyl spacers. On the contrary, the 1-,5- or 2-,6
      connections of triads 1a and 1c allow for an efficient pi-conjugation between the
      active units that extends over the entire planar system. These two molecules tend
      to aggregate in aromatic solvents by pi-pi stacking, giving rise to J-type
      oligomers. Photoexcitation of the Pc units of 1a-c results in the formation of
      the Pc.+-AQ.- charge transfer state. We have demonstrated that the kinetics of
      these electron transfer reactions is greatly dependent on the aggregation status
      of the triads.

PMID- 17002362
TI  - The Si-Si effect on ionization of beta-disilanyl sulfides and selenides.
AB  - The ionization energies of conformationally constrained, newly synthesized beta
      disilanyl sulfides and selenides were determined by photoelectron spectroscopy.
      These ionization energies reflect substantial (0.53-0.75 eV) orbital
      destabilizations. The basis for these destabilizations was investigated by
      theoretical calculations, which reveal geometry-dependent interaction between
      sulfur or selenium lone pair orbitals and sigma-orbitals, especially Si-Si sigma
      orbitals. These results presage facile redox chemistry for these compounds and
      significantly extend the concept of sigma-stabilization of electron-deficient
      centers.

PMID- 17002363
TI  - Behavior of polycatalytic assemblies in a substrate-displaying matrix.
AB  - We describe polycatalytic assemblies, comprising one or two streptavidin
      molecules and two to six attached nucleic acid catalysts (deoxyribozymes), with
      phosphodiesterase activity. When exposed to a matrix covered at high densities
      with oligonucleotide substrates, these molecules diffuse through the matrix
      continuously cleaving the substrate at rates comparable to those of individual
      catalysts in solution. Rates of diffusion (movement), processivity, and resident
      times of assemblies can be controlled through the number of catalytic units and
      the length of substrate/product recognition regions. The assemblies were
      characterized at the ensemble level using surface plasmon resonance.

PMID- 17002364
TI  - Ionic core-shell dendrimers with an octacationic core as noncovalent supports for
      homogeneous catalysts.
AB  - Ionic core-shell dendrimers with an octacationic core have been applied as
      noncovalent supports for homogeneous catalysts. Catalytically active
      arylpalladium complexes, which bear a tethered sulfato group, were noncovalently
      attached to the ionic core-shell dendritic supports via a straightforward ion
      exchange reaction under mild conditions. Diagnostic shifts in (1)H NMR and
      Overhauser contacts show that the sulfato groups of the catalysts are located
      close to the octacationic core of the dendritic support in the resulting
      assemblies. The location of the catalytic Pd(II) sites has been varied via two
      strategies: by increasing the dendrimer generation and/or by shortening of the
      sulfato tether. In addition, a metallodendritic assembly was prepared, which
      bears an alternative shell of apolar dodecyl groups. Both the dendrimer size and
      the nature of the dendritic shell have no influence on the binding properties of
      the dendritic supports, i.e., the octacationic dendrimers of generations 1-3 form
      discrete 1:8 assemblies with the arylpalladium complexes. The structural aspects
      and the nature of the metallodendritic assemblies have been studied by means of
      pulse gradient spin-echo NMR diffusion methods, Overhauser spectroscopy, and
      electron microscopy (TEM). These techniques showed that the dendritic supports
      and arylpalladium complexes are strongly associated in solution to give
      unimolecular assemblies of nanoscopic dimensions. Membrane dialysis can recover
      these metallodendritic assemblies due to their nanoscopic size. The catalytic
      performances of the metallodendritic assemblies are comparable, but slightly
      lower than the performance of the unsupported catalyst.

PMID- 17002365
TI  - Soluble narrow band gap and blue propylenedioxythiophene-cyanovinylene polymers
      as multifunctional materials for photovoltaic and electrochromic applications.
AB  - A family of soluble narrow band gap donor-acceptor conjugated polymers based on
      dioxythiophenes and cyanovinylenes is reported. The polymers were synthesized
      using Knoevenagel polycondensation or Yamamoto coupling polymerizations to yield
      polymers with molecular weights on the order of 10 000-20 000 g/mol, which
      possess solubility in common organic solvents. Thin film optical measurements
      revealed narrow band gaps of 1.5-1.8 eV, which gives the polymers a strong
      overlap of the solar spectrum. The energetic positions of the band edges were
      determined by cyclic voltammetry and differential pulse voltammetry and
      demonstrate that the polymers are both air stable and show a strong propensity
      for photoinduced charge transfer to fullerene acceptors. Such measurements also
      suggest that the polymers can be both p- and n-type doped, which is supported by
      spectroelectrochemical results. These polymers have been investigated as electron
      donors in photovoltaic devices in combination with PCBM ([6,6]-phenyl C(61)
      butyric acid methyl ester) as an electron acceptor based on the near ideal band
      structures designed into the polymers. Efficiencies as high as 0.2% (AM1.5) with
      short circuit current densities as high as 1.2-1.3 mA/cm(2) have been observed in
      polymer/PCBM (1:4 by weight) devices and external quantum efficiencies of more
      than 10% have been observed at wavelengths longer than 600 nm. The electrochromic
      properties of the narrow band gap polymers are also of interest as the polymers
      show three accessible color states changing from an absorptive blue or purple in
      the neutral state to a transmissive sky-blue or gray in the oxidized and reduced
      forms. The wide electrochemical range of electrochromic activity coupled with the
      strong observed changes in transmissivity between oxidation states makes these
      materials potentially interesting for application to electrochromic displays.

PMID- 17002366
TI  - Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA
      delivery.
AB  - The safe and efficient delivery of DNA remains the major barrier to the clinical
      application of non-viral gene therapy. Here, we present novel, biodegradable
      polymers for gene delivery that are capable of simple graft modification and
      demonstrate the ability to respond to intracellular conditions. We synthesized
      poly(beta-amino ester)s using a new amine monomer, 2-(pyridyldithio)-ethylamine
      (PDA). These cationic, degradable polymers contain pyridyldithio functionalities
      in the side chains that react with high specificity toward thiol ligands. This
      reactivity is demonstrated using both mercaptoethylamine (MEA) and the thiol
      peptide RGDC, a ligand that binds with high affinity to certain integrin
      receptors. These two polymer derivatives displayed strong DNA binding as
      determined using electrophoresis and dye exclusion assays. In addition, the MEA
      based polymer and plasmid DNA were shown to self-assemble into cationic complexes
      with effective diameters as low as 100 nm. Furthermore, this DNA binding ability
      was substantially reduced in response to intracellular glutathione
      concentrations, which may aid in DNA unpackaging inside the cell. These complexes
      also displayed low cellular toxicity and were able to mediate transfection at
      levels comparable to PEI in human hepatocellular carcinoma cells. These results
      suggest that PDA-based poly(beta-amino ester)s may serve as a modular platform
      for polymer-mediated gene delivery.

PMID- 17002367
TI  - Arginine methylation in a beta-hairpin peptide: implications for Arg-pi
      interactions, DeltaCp(o), and the cold denatured state.
AB  - Arginine methylation is a common post-translational modification that plays a
      role in many cellular processes through mediation of protein-protein
      interactions. There is still a dearth of structural information as to its role in
      mediating such interactions, but the available data suggest a possible role of
      cation-pi interactions in the recognition of methylated arginine. Hence, the
      effect of arginine methylation on its interaction with tryptophan has been
      investigated within the context of a beta-hairpin peptide. Arginine methylation
      was found to enhance the stacking interaction between the cationic guanidinium
      functionality of arginine and the indole ring of tryptophan, resulting in
      structural stabilization of the hairpin. Thermodynamic analysis reveals more
      favorable entropy of hairpin folding with arginine methylation, a more negative
      change in heat capacity for folding, and a modest decrease in enthalpic driving
      force. This is consistent with enhanced stacking and hydrophobic interactions
      through increased surface area of the guanidinium moiety and greater
      delocalization of positive charge. In addition, these peptides exhibit
      significant cold denaturation, which can be accounted for by the inclusion of an
      expression of temperature-dependent DeltaC(p) in the thermodynamic analysis.

PMID- 17002368
TI  - Conical intersection control of heterocyclic photochemical bond scission.
AB  - The photochemistry of the heterocycle 5,6-dihydro-1-methyl-5,5-diphenylpyridin
      2(1H)-one (compound 1 in the text) leads to two competitive reactions (the
      reactions are depicted in the Introduction to the article). These arise from
      fission of bond a, between the nitrogen (N-6) and C-1, and bond b, between C-4,
      with the two phenyl substituents, and C-5, adjacent to the nitrogen. Scission of
      bond a alone leads to a zwitterionic intermediate which can be trapped by
      nucleophiles, while cleavage of bonds a and b together affords two fragments--a
      ketene and an imine. The ketene could be intercepted with nucleophiles and the
      imine trimerized. Computation reveals little weakening of bonds a and b. But as
      stretching begins, conical intersections are encountered, leading to ground-state
      products.

PMID- 17002369
TI  - Binding of a designed substrate analogue to diisopropyl fluorophosphatase:
      implications for the phosphotriesterase mechanism.
AB  - A wide range of organophosphorus nerve agents, including Soman, Sarin, and Tabun
      is efficiently hydrolyzed by the phosphotriesterase enzyme diisopropyl
      fluorophosphatase (DFPase) from Loligo vulgaris. To date, the lack of available
      inhibitors of DFPase has limited studies on its mechanism. The de novo design,
      synthesis, and characterization of substrate analogues acting as competitive
      inhibitors of DFPase are reported. The 1.73 A crystal structure of O,O
      dicyclopentylphosphoroamidate (DcPPA) bound to DFPase shows a direct coordination
      of the phosphoryl oxygen by the catalytic calcium ion. The binding mode of this
      substrate analogue suggests a crucial role for electrostatics in the orientation
      of the ligand in the active site. This interpretation is further supported by the
      crystal structures of double mutants D229N/N120D and D229N/N175D, designed to
      reorient the electrostatic environment around the catalytic calcium. The
      structures show no differences in their calcium coordinating environment,
      although they are enzymatically inactive. Additional double mutants E21Q/N120D
      and E21Q/N175D are also inactive. On the basis of these crystal structures and
      kinetic and mutagenesis data as well as isotope labeling we propose a new
      mechanism for DFPase activity. Calcium coordinating residue D229, in concert with
      direct substrate activation by the metal ion, renders the phosphorus atom of the
      substrate susceptible for attack of water, through generation of a phosphoenzyme
      intermediate. Our proposed mechanism may be applicable to the structurally
      related enzyme paraoxonase (PON), a component of high-density lipoprotein (HDL).

PMID- 17002370
TI  - When is water not water? Exploring water confined in large reverse micelles using
      a highly charged inorganic molecular probe.
AB  - The interior water pool of aerosol OT (AOT) reverse micelles tends toward bulk
      water properties as the micelle size increases. Thus, deviations from bulk water
      behavior in large reverse micelles are less expected than in small reverse
      micelles. Probing the interior water pool of AOT reverse micelles with a highly
      charged decavanadate (V(10)) oligomer using (51)V NMR spectroscopy shows distinct
      changes in solute environment. For example, when an acidic stock solution of
      protonated V(10) is placed in a reverse micelle, the (51)V chemical shifts show
      that the V(10) is deprotonated consistent with a decreased proton concentration
      in the intramicellar water pool. Results indicate that a proton gradient exists
      inside the reverse micelles, leaving the interior neutral while the interfacial
      region is acidic.

PMID- 17002372
TI  - Synthesis and characterization of iron silicon boron (Fe5Si2B) and iron boride
      (Fe3B) nanowires.
AB  - Single-crystal iron silicon boron (Fe(5)Si(2)B) and iron boride (Fe(3)B)
      nanowires were synthesized by a chemical vapor deposition (CVD) method on either
      silicon dioxide (SiO(2)) on silicon (Si) or Si substrates without introducing any
      catalysts. FeI(2) and BI(3) were used as precursors. The typical size of the
      nanowires is about 5-50 nm in width and 1-20 mum in length. Different kinds of Fe
      Si-B and Fe-B structures were synthesized by adjusting the ratio of FeI(2) vapor
      to BI(3) vapor. Single-crystal Fe(5)Si(2)B nanowires formed when the FeI(2)
      sublimator temperature was kept in the range of 540-570 degrees C. If the FeI(2)
      sublimator temperature was adjusted in the range of 430-470 degrees C, single
      crystal Fe(3)B nanowires were produced. Fe(3)B nanowires grow from
      polycrystalline Fe(5)SiB(2) particles, while Fe(5)Si(2)B nanowires grow out of
      the Fe(5)Si(2)B layers, which are attached to triangle shaped FeSi particles.
      Both the ratio of FeI(2) vapor to BI(3) vapor and the formation of the particles
      (Fe(5)SiB(2) particles for the growth of Fe(3)B nanowires, FeSi particles for the
      growth of Fe(5)Si(2)B nanowires) are critical for the growth of Fe(3)B and
      Fe(5)Si(2)B nanowires. The correct FeI(2) vapor to BI(3) vapor ratio assures the
      desired phase form, while the particles provide preferential sites for adsorption
      and nucleation of Fe(3)B or Fe(5)Si(2)B molecules. Fe(3)B or Fe(5)Si(2)B
      nanowires grow due to the preferred growth direction of <110>.

PMID- 17002371
TI  - Thermodynamic basis for promiscuity and selectivity in protein-protein
      interactions: PDZ domains, a case study.
AB  - Like other protein-protein interaction domains, PDZ domains are involved in many
      key cellular processes. These processes often require that specific multiprotein
      complexes be assembled, a task that PDZ domains accomplish by binding to specific
      peptide motifs in target proteins. However, a growing number of experimental
      studies show that PDZ domains (like other protein-protein interaction domains)
      can engage in a variety of interactions and bind distinct peptide motifs. Such
      promiscuity in ligand recognition raises intriguing questions about the molecular
      and thermodynamic mechanisms that can sustain it. To identify possible sources of
      promiscuity and selectivity underlying PDZ domain interactions, we performed
      molecular dynamics simulations of 20 to 25 ns on a set of 12 different PDZ domain
      complexes (for the proteins PSD-95, Syntenin, Erbin, GRIP, NHERF, Inad,
      Dishevelled, and Shank). The electrostatic, nonpolar, and configurational entropy
      binding contributions were evaluated using the MM/PBSA method combined with a
      quasi-harmonic analysis. The results revealed that PDZ domain interactions are
      characterized by overwhelmingly favorable nonpolar contributions and almost
      negligible electrostatic components, a mix that may readily sustain promiscuity.
      In addition, despite the structural similarity in fold and in recognition modes,
      the entropic and other dynamical aspects of binding were remarkably variable not
      only across PDZ domains but also for the same PDZ domain bound to distinct
      ligands. This variability suggests that entropic and dynamical components can
      play a role in determining selectivity either of PDZ domain interactions with
      peptide ligands or of PDZ domain complexes with downstream effectors.

PMID- 17002373
TI  - The mechanism of the phosphine-free palladium-catalyzed hydroarylation of
      alkynes.
AB  - The mechanism of the Pd-catalyzed hydroarylation and hydrovinylation reaction of
      alkynes has been studied by a combination of experimental and theoretical methods
      (B3LYP), with an emphasis on the phosphine-free version. The regioselectivity of
      the hydroarylation and hydrovinylation shows unexpected differences, which could
      be attributed mainly to the higher steric demand of the cyclohexenyl group as
      compared to the phenyl group. Hydroarylation of alpha,beta-acetylenic carbonyl
      substrates yields a very unusual anti-Michael selectivity, which is shown to
      result from reaction of the nonconjugated double bond, leaving the conjugation
      intact. In all cases were the regioselectivities reproduced by the calculations.

PMID- 17002374
TI  - Photo-CIDNP MAS NMR in intact cells of Rhodobacter sphaeroides R26: molecular and
      atomic resolution at nanomolar concentration.
AB  - Photochemically induced dynamic nuclear polarization (photo-CIDNP) is observed in
      photosynthetic reaction centers of the carotenoid-less strain R26 of the purple
      bacterium Rhodobacter sphaeroides by (13)C solid-state NMR at three different
      magnetic fields (4.7, 9.4, and 17.6 T). The signals of the donor appear enhanced
      absorptive (positive) and of the acceptor emissive (negative). This spectral
      feature is in contrast to photo-CIDNP data of reactions centers of Rhodobacter
      sphaeroides wildtype reported previously (Prakash, S.; Alia; Gast, P.; de Groot,
      H. J. M.; Jeschke, G.; Matysik, J. J. Am. Chem. Soc. 2005, 127, 14290-14298) in
      which all signals appear emissive. The difference is due to an additional
      mechanism occurring in RCs of R26 in the long-living triplet state of the donor,
      allowing for spectral editing by different enhancement mechanisms. The overall
      shape of the spectra remains independent of the magnetic field. The strongest
      enhancement is observed at 4.7 T, enabling the observation of photo-CIDNP
      enhanced NMR signals from reaction center cofactors in entire bacterial cells
      allowing for detection of subtle changes in the electronic structure at nanomolar
      concentration of the donor cofactor. Therefore, we establish in this paper photo
      CIDNP MAS NMR as a method to study the electronic structure of photosynthetic
      cofactors at the molecular and atomic resolution as well as at cellular
      concentrations.

PMID- 17002375
TI  - Lanthanides to quantum dots resonance energy transfer in time-resolved fluoro
      immunoassays and luminescence microscopy.
AB  - A time-resolved fluoro-immunoassay (TR-FIA) format is presented based on
      resonance energy transfer from visible emitting lanthanide complexes of europium
      and terbium, as energy donors, to semiconductor CdSe/ZnS core/shell nanocrystals
      (quantum dots, QD), as energy acceptors. The spatial proximity of the donor
      acceptor pairs is obtained through the biological recognition process of biotin,
      coated at the surface of the dots (Biot-QD), and streptavidin labeled with the
      lanthanide markers (Ln-strep). The energy transfer phenomenon is evident from
      simultaneous lanthanide emission quenching and QD emission sensitization with a
      1000-fold increase of the QD luminescence decay time reaching the hundred mus
      regime. Delayed emission detection allows for quantification of the recognition
      process and demonstrated a nearly quantitative association of the biotins to
      streptavidin with sensitivity limits reaching 1.2 pM of QD. Spectral
      characterization permits calculation of the energy transfer parameters. Extremely
      large Forster radii (R(0)) values were obtained for Tb (104 A) and Eu (96 A) as a
      result of the relevant spectral overlap of donor emission and acceptor
      absorption. Special attention was paid to interactions with the varying
      constituents of the buffer for sensitivity and transfer efficiency optimization.
      The energy transfer phenomenon was also monitored by time-resolved luminescence
      microscopy experiments. At elevated concentration (>10(-)(5) M), Tb-strep
      precipitated in the form of pellets with long-lived green luminescence, whereas
      addition of Biot-QD led to red emitting pellets, with long excited-state decay
      times. The Ln-QD donor-acceptor hybrids appear as highly sensitive analytical
      tools both for TR-FIA and time-resolved luminescence microscopy experiments.

PMID- 17002376
TI  - Sum frequency generation vibrational spectroscopic and high-pressure scanning
      tunneling microscopic studies of benzene hydrogenation on Pt(111).
AB  - Sum frequency generation (SFG) vibrational spectroscopy and high-pressure
      scanning tunneling microscopy (HP-STM) have been used in combination for the
      first time to study a catalytic reaction. These techniques have been able to
      identify surface intermediates in situ during benzene hydrogenation on a Pt(111)
      single-crystal surface at Torr pressures. In a background of 10 Torr of benzene,
      STM is able to image small ordered regions corresponding to the c(2 radical3 x
      3)rect structure in which each molecule is chemisorbed at a bridge site. In
      addition, individual benzene molecules are also observed between the ordered
      regions. These individual molecules are assumed to be physisorbed benzene on the
      basis of the SFG results showing both chemisorbed and physisorbed molecules. The
      surface becomes too mobile to image upon addition of hydrogen but is determined
      to have physisorbed and chemisorbed benzene present by SFG. It was
      spectroscopically determined that heating the platinum surface after poisoning
      with CO displaces benzene molecules. The high-coverage pure CO structure of
      (radical19 x radical19)R23.4 degrees imaged with STM is a verification of
      spectroscopic measurements.

PMID- 17002377
TI  - The catalytic mechanism of peptidylglycine alpha-hydroxylating monooxygenase
      investigated by computer simulation.
AB  - The molecular basis of the hydroxylation reaction of the Calpha of a C-terminal
      glycine catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM) was
      investigated using hybrid quantum-classical (QM-MM) computational techniques. We
      have identified the most reactive oxygenated species and presented new insights
      into the hydrogen abstraction (H-abstraction) mechanism operative in PHM. Our
      results suggest that O(2) binds to Cu(B) to generate Cu(B)(II)-O(2)(.-) followed
      by electron transfer (ET) from Cu(A) to form Cu(B)(I)-O(2)(.-). The computed
      potential energy profiles for the H-abstraction reaction for Cu(B)(II)-O(2)(.-),
      Cu(B)(I)-O(2)(.-), and [Cu(B)(II)-OOH](+) species indicate that none of these
      species can be responsible for abstraction. However, the latter species can
      spontaneously form [Cu(B)O](+2) (which consists of a two-unpaired-electrons
      [Cu(B)O](+) moiety ferromagnetically coupled with a radical cation located over
      the three Cu(B) ligands, in the quartet spin ground state) by abstracting a
      proton from the surrounding solvent. Both this monooxygenated species and the one
      obtained by reduction with ascorbate, [Cu(B)O](+), were found to be capable of
      carrying out the H-abstraction; however, whereas the former abstracts the
      hydrogen atom concertedly with almost no activation energy, the later forms an
      intermediate that continues the reaction by a rebinding step. We propose that the
      active species in H-abstraction in PHM is probably [Cu(B)O](+2) because it is
      formed exothermically and can concertedly abstract the substrate HA atom with the
      lower overall activation energy. Interestingly, this species resembles the active
      oxidant in cytochrome P450 enzymes, Compound I, suggesting that both PHM and
      cytochrome P450 enzymes may carry out substrate hydroxylation by using a similar
      mechanism.

PMID- 17002378
TI  - To achieve stable spherical clusters: general principles and experimental
      confirmations.
AB  - General principles for designing stable highly symmetrical clusters are proposed.
      This approach takes advantage of both the extra stability of cage aromaticity and
      the good geometrical balance between the outer cage and the endohedral atom. The
      applicability of these design principles was confirmed by gas-phase experimental
      observations on group 14 element cages with endohedral Al's and also is
      illustrated by many literature examples of diverse systems.

PMID- 17002379
TI  - Incremental solvation of nonionized and zwitterionic glycine.
AB  - Microsolvation and combined microsolvation-continuum approaches are employed in
      order to examine the structures and relative energies of nonionized (N) and
      zwitterionic (Z) glycine clusters. Bridging structures are predicted to be the
      global minima after 3-5 discrete water molecules are included in the
      calculations. Calculations incorporating electron correlation stabilize the
      zwitterionic structures by about 7-9 kcal/mol relative to the N structures
      regardless of the number of discrete water molecules considered. Continuum
      calculations stabilize the Z structures relative to N structures; this effect
      decreases as the number of discrete water molecules is increased. Eight water
      molecules do not appear to fully solvate glycine.

PMID- 17002380
TI  - Gate dielectric chemical structure-organic field-effect transistor performance
      correlations for electron, hole, and ambipolar organic semiconductors.
AB  - This study describes a general approach for probing semiconductor-dielectric
      interfacial chemistry effects on organic field-effect transistor performance
      parameters using bilayer gate dielectrics. Organic semiconductors exhibiting p-/n
      type or ambipolar majority charge transport are grown on six different bilayer
      dielectric structures consisting of various spin-coated polymers/HMDS on 300 nm
      SiO(2)/p(+)-Si, and are characterized by AFM, SEM, and WAXRD, followed by
      transistor electrical characterization. In the case of air-sensitive (generally
      high LUMO energy) n-type semiconductors, dielectric surface modifications induce
      large variations in the corresponding OTFT performance parameters although the
      film morphologies and microstructures remain similar. In marked contrast, the
      device performance of air-stable n-type and p-type semiconductors is not
      significantly affected by the same dielectric surface modifications. Among the
      bilayer dielectric structures examined, nonpolar polystyrene coatings on SiO(2)
      having minimal gate leakage and surface roughness significantly enhance the
      mobilities of overlying air-sensitive n-type semiconductors to as high as
      approximately 2 cm(2)/(V s) for alpha,omega
      diperfluorohexylcarbonylquaterthiophene polystyrene/SiO(2). Electron trapping due
      to silanol and carbonyl functionalities at the semiconductor-dielectric interface
      is identified as the principal origin of the mobility sensitivity to the various
      surface chemistries in the case of n-type semiconductors having high LUMO
      energies. Thiophene-based n-type semiconductors exhibiting similar film
      morphologies and microstructures on various bilayer gate dielectrics therefore
      provide an incisive means to probe TFT performance parameters versus
      semiconductor-dielectric interface relationships.

PMID- 17002381
TI  - Reversible pH-driven conformational switching of tethered superoxide dismutase
      with gold nanoparticle enhanced surface plasmon resonance spectroscopy.
AB  - A new class of surface-immobilized protein nanomachines can be reversibly
      actuated by cycling the solution pH between 2.5 and 12.3, which induces a
      conformational change, thereby modulating the thickness of superoxide dismutase
      (SOD1) tethered to the Au thin film. By placing Au nanoparticles (AuNP) atop the
      immobilized SOD1 by means of a gold-thiol assembly, the nanoscale motion of SOD1
      at the interface produces mechanical work to lift and then lower the AuNP from
      the Au substrate by a distance of ca. 3 nm and transduces this motion into an
      easily measurable reflectivity change in the surface plasmon resonance (SPR)
      spectrum. As-made supported conjugate consisting of SOD1 and AuNP is quite robust
      and stable, and its operation in response to pH variations, which mirrors the
      conformational changes of responsive SOD1 at the interface, is found to be highly
      reversible and reproducible. This is the first demonstration of the development
      of novel solid-state sensors and/or switching devices based on substrate-bound
      protein conformational changes and AuNP enhanced SPR spectroscopy.

PMID- 17002382
TI  - Luminescent triarylborane-functionalized polystyrene: synthesis, photophysical
      characterization, and anion-binding studies.
AB  - A new class of highly fluorescent triarylborane polymers has been prepared from
      trimethylsilyl-substituted polystyrene via a modular approach that involves
      selective polymer modification reactions with organometallic reagents. The
      photophysical properties, environmental stability, and the Lewis acidity of the
      boron sites have been tailored through modifications in the substitution pattern
      on boron. The photophysical properties are indicative of electronic communication
      between the chromophores attached to polystyrene, which has been exploited for
      the efficient probing of fluoride and cyanide in the micromolar concentration
      range.

PMID- 17002383
TI  - Well-defined chiral spiro iridium/phosphine-oxazoline cationic complexes for
      highly enantioselective hydrogenation of imines at ambient pressure.
AB  - New chiral phosphine-oxazoline ligands (7, SIPHOX) with a rigid and bulky
      spirobiindane scaffold were synthesized, starting with optically pure 7
      diphenylphosphino-7'-trifluoromethanesulfonyloxyl-1,1'-spirobiindane, in four
      steps in 40-64% overall yield. Iridium complexes of 7, the chiral analogues of
      the Crabtree catalyst, were generated by coordination of ligands 7 and
      [Ir(COD)Cl](2) in the presence of sodium tetrakis-3,5
      bis(trifluoromethyl)phenylborate. The complexes were characterized by NMR, ESI
      MS, and X-ray diffraction analysis. The Ir-SIPHOX complexes can catalyze the
      hydrogenation of acyclic N-aryl ketimines under ambient pressure with excellent
      enantioselectivities (up to 97% ee) and full conversions. This result represents
      the highest enantioselectivity and the first example of the hydrogenation of
      imines catalyzed by chiral analogues of the Crabtree catalyst at ambient
      pressure. Studies on the stability of the catalysts revealed that the catalysts
      Ir-SIPHOX are very stable and resistant to the formation of inactive trimers
      under hydrogenation conditions. On the basis of the X-ray diffraction analysis of
      the structures of catalysts and amine products, a rational explanation for the
      enantiocontrol of the chiral catalysts in the hydrogenation of imines is
      proposed.

PMID- 17002384
TI  - Raman thermometry measurements of free evaporation from liquid water droplets.
AB  - Recent theoretical and experimental studies of evaporation have suggested that on
      average, molecules in the higher-energy tail of the Boltzmann distribution are
      more readily transferred into the vapor during evaporation. To test these
      conclusions, the evaporative cooling rates of a droplet train of liquid water
      injected into vacuum have been studied via Raman thermometry. The resulting
      cooling rates are fit to an evaporative cooling model based on Knudsen's maximum
      rate of evaporation, in which we explicitly account for surface cooling. We have
      determined that the value of the evaporation coefficient (gamma(e)) of liquid
      water is 0.62 +/- 0.09, confirming that a rate-limiting barrier impedes the
      evaporation rate. Such insight will facilitate the formulation of a microscopic
      mechanism for the evaporation of liquid water.

PMID- 17002385
TI  - Functionalization of single-walled carbon nanotubes "on water".
AB  - Single-walled carbon nanotubes (SWNTs) are exfoliated and functionalized into
      small bundles and individuals by vigorous stirring "on water" in the presence of
      a substituted aniline and an oxidizing agent. This is an example of an "on water"
      reaction that leads to functionalized SWNTs, and it represents a "green", or
      environmentally friendly, process. A variety of reaction conditions were
      explored. The products were analyzed with Raman, UV-vis-NIR, and X-ray
      photoelectron spectroscopies, atomic force and transmission electron
      microscopies, and thermogravimetric analysis.

PMID- 17002386
TI  - Synthesis of ordered mesoporous Fe3O4 and gamma-Fe2O3 with crystalline walls
      using post-template reduction/oxidation.
AB  - Ordered mesoporous Fe(3)O(4) with crystalline walls (inverse spinel structure)
      has been synthesized for the first time, representing to the best of our
      knowledge, the first synthesis of a reduced mesoporous iron oxide. Synthesis was
      achieved by reducing ordered mesoporous alpha-Fe(2)O(3) (corundum structure) to
      Fe(3)O(4) spinel then to gamma-Fe(2)O(3) by oxidation, while preserving the
      ordered mesostructure and crystalline walls throughout. Such solid/solid
      transformations demonstrate the stability of the mesostructure to structural
      phase transitions from the hexagonal close packed oxide subarray of alpha
      Fe(2)O(3) (corundum structure) to the cubic close packed subarray of Fe(3)O(4)
      spinel and gamma-Fe(2)O(3). Preliminary magnetic measurements reveal that the
      spins in both Fe(3)O(4) and gamma-Fe(2)O(3) are frozen at 295 K, despite the wall
      thickness (7 nm) being less than the lower limit for such freezing in
      corresponding nanoparticles (>8 nm).

PMID- 17002388
TI  - Controlling the growth of single crystalline nanoribbons of copper
      tetracyanoquinodimethane for the fabrication of devices and device arrays.
AB  - In this paper, (1) a simple and controllable method to synthesize single
      crystalline nanoribbons of CuTCNQ in a large area was demonstrated by using a
      physical and chemical vapor combined deposition technique. (2) Nanoribbons
      synthesized by this method were identified to belong to phase I. (3) Devices and
      device arrays of nanoribbons were in situ fabricated by this method using gap
      electrodes and gap electrode arrays. (4) Current-voltage characteristics of
      crystalline devices and device arrays of nanoribbons exhibited semiconductor
      properties, and this conclusion was further confirmed by the results of devices
      based on an individual nanoribbon or microribbon of CuTCNQ (phase I). The
      controllable synthesis of nanoribbons for the in situ fabrication of crystalline
      nanodevices and device arrays will be attractive for nanoelectronics. Moreover,
      semiconductor current-voltage characteristics of the nanoribbons will be
      beneficial to the understanding of CuTCNQ.

PMID- 17002387
TI  - Structure determination of protein-ligand complexes by transferred paramagnetic
      shifts.
AB  - Rational drug design depends on the knowledge of the three-dimensional (3D)
      structure of complexes between proteins and lead compounds of low molecular
      weight. A novel nuclear magnetic resonance (NMR) spectroscopy strategy based on
      the paramagnetic effects from lanthanide ions allows the rapid determination of
      the 3D structure of a small ligand molecule bound to its protein target in
      solution and, simultaneously, its location and orientation with respect to the
      protein. The method relies on the presence of a lanthanide ion in the protein
      target and on fast exchange between bound and free ligand. The binding affinity
      of the ligand and the paramagnetic effects experienced in the bound state are
      derived from concentration-dependent (1)H and (13)C spectra of the ligand at
      natural isotopic abundance. Combined with prior knowledge of the crystal or
      solution structure of the protein and of the magnetic susceptibility tensor of
      the lanthanide ion, the paramagnetic data define the location and orientation of
      the bound ligand molecule with respect to the protein from simple 1D NMR spectra.
      The method was verified with the ternary 30 kDa complex between the lanthanide
      labeled N-terminal domain of the epsilon exonuclease subunit from the Escherichia
      coli DNA polymerase III, the subunit theta, and thymidine. The binding mode of
      thymidine was found to be very similar to that of thymidine monophosphate present
      in the crystal structure.

PMID- 17002389
TI  - Highly enantioselective synthesis of atropisomeric anilide derivatives through
      catalytic asymmetric N-arylation: conformational analysis and application to
      asymmetric enolate chemistry.
AB  - In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)(2) catalyst, N-arylation (aromatic
      amination) of various o-tert-butylanilides with p-iodonitrobenzene proceeds with
      high enantioselectivity (88-96% ee) to give atropisomeric N-(p
      nitrophenyl)anilides having an N-C chiral axis in good yields. Atropisomeric
      anilide products highly prefer to exist as the E-rotamer which has trans-disposed
      o-tert-butylphenyl group and carbonyl oxygen. The application of the present
      catalytic enantioselective N-arylation to an intramolecular version gives
      atropisomeric lactam derivatives with high optical purity (92-98% ee). The
      reaction of the lithium enolate prepared from the atropisomeric anilide and
      lactam products with various alkyl halides gives alpha-alkylated products with
      high diastereoselectivity (diastereomer ratio = 13:1 to 46:1).

PMID- 17002390
TI  - A modular strategy for tailoring fluorescent biosensors from ribonucleopeptide
      complexes.
AB  - Fluorescent biosensors that facilitate reagentless sensitive detection of small
      molecules are crucial tools in the areas of therapeutics and diagnostics.
      However, construction of fluorescent biosensors with desired characteristics,
      that is, detection wavelengths and concentration ranges for ligand detection,
      from macromolecular receptors is not a straightforward task. An ATP-binding
      ribonucleopeptide (RNP) receptor was converted to a fluorescent ATP sensor
      without chemically modifying the nucleotide in the ATP-binding RNA. The RNA
      subunit of the ATP-binding RNP and a peptide modified with a pyrenyl group formed
      a stable fluorescent RNP complex that showed an increase in the fluorescence
      intensity upon binding to ATP. The strategy to convert the ATP-binding RNP
      receptor to a fluorescent ATP sensor was applied to generate fluorescent ATP
      binding RNP libraries by using a pool of RNA subunits obtained from the in vitro
      selection of ATP-binding RNPs and a series of fluorophore-modified peptide
      subunits. Simple screening of the fluorescent RNP library based on the
      fluorescence emission intensity changes in the absence and presence of the ligand
      afforded fluorescent ATP or GTP sensors with emission wavelengths varying from
      390 to 670 nm. Screening of the fluorescence emission intensity changes in the
      presence of increasing concentrations of ATP allowed titration analysis of the
      fluorescent RNP library, which provided ATP sensors responding at wide
      concentration ranges of ATP. The combinatorial strategy using the modular RNP
      receptor reported here enables tailoring of a fluorescent sensor for a specific
      ligand without knowledge of detailed structural information for the
      macromolecular receptor.

PMID- 17002391
TI  - Mechanism for catechol ring cleavage by non-heme iron intradiol dioxygenases: a
      hybrid DFT study.
AB  - The mechanism of the catalytic reaction of protocatechuate 3,4-dioxygenase (3,4
      PCD), a representative intradiol dioxygenase, was studied with the hybrid density
      functional method B3LYP. First, a smaller model involving only the iron first
      shell ligands (His460, His462, and Tyr408) and the substrates (catechol and
      dioxygen) was used to probe various a priori plausible reaction mechanisms. Then,
      an extended model involving also the most important second-shell groups (Arg457,
      Gln477, and Tyr479) was used for the refinement of the preselected mechanisms.
      The computational results suggest that the chemical reactions constituting the
      catalytic cycle of intradiol dioxygenases involve: (1) binding of the substrate
      as a dianion, in agreement with experimental suggestions, (2) binding of dioxygen
      to the metal aided by an electron transfer from the substrate to O(2), (3)
      formation of a bridging peroxo intermediate and its conformational change, which
      opens the coordination site trans to His462, (4) binding of a neutral XOH ligand
      (H(2)O or Tyr447) at the open site, (5) proton transfer from XOH to the
      neighboring peroxo ligand yielding the hydroperoxo intermediate, (6) a Criegee
      rearrangement leading to the anhydride intermediate, and (7) hydrolysis of the
      anhydride to the final acyclic product. One of the most important results
      obtained is that the Criegee mechanism requires an in-plane orientation of the
      four atoms (two oxygen and two carbon atoms) mainly involved in the reaction.
      This orientation yields a good overlap between the two sigma orbitals involved, C
      C sigma and O-O sigma, allowing an efficient electron flow between them. Another
      interesting result is that under some conditions, a homolytic O-O bond cleavage
      might compete with the Criegee rearrangement. The role of the second-shell
      residues and the substituent effects are also discussed.

PMID- 17002392
TI  - Hydrogen-bond-directed highly stereoselective synthesis of Z-enamides via Pd
      catalyzed oxidative amidation of conjugated olefins.
AB  - An efficient procedure for the preparation of Z-enamides has been developed,
      involving the reaction of primary amides with conjugated olefins using a Pd/Cu
      cocatalyst system. It was found that certain additives, such as phosphine oxides
      and phosphonates, increase the efficiency of the reaction in nonpolar solvents
      under an oxygen atmosphere, thus producing a variety of Z-enamides in high yields
      with excellent stereoselectivity under Wacker-type conditions. The oxidative
      amidation reaction has a broad substrate scope, allowing alkyl, aryl, and vinyl
      amides to react with olefins conjugated with ester, amide, phosphonate, and
      ketone groups. The notable preference for the formation of Z-enamides is
      presumably due to the presence of an intramolecular hydrogen bond between the
      amido proton and the carbonyl oxygen. The energy difference between two plausible
      sigma-alkylamidopalladium intermediates, leading to Z- and E-isomeric enamide
      products, respectively, was calculated to be 4.18 kcal/mol. The beta-hydride
      elimination step is assumed to be a stereochemistry-determining step in the
      overall oxidative amidation process, with the energy level for the transition
      state leading to the Z-enamide being 5.35 kcal/mol lower than that leading to the
      E-isomer. The efficiency of photoisomerization between Z- and E-enamides was
      observed to be largely dependent on the substrates' substituents, and certain E
      enamides could be obtained in synthetically useful yields by photoirradiation of
      Z-isomers. Synthetic application of the present method was successfully
      demonstrated by a direct formal synthesis of cis-CJ-15,801.

PMID- 17002393
TI  - Molded, high surface area polymer electrolyte membranes from cured liquid
      precursors.
AB  - Polymer electrolyte membranes (PEMs) for fuel cells have been synthesized from
      easily processable, 100% curable, low molecular weight reactive liquid precursors
      that are photochemically cured into highly proton conductive solid membranes. The
      liquid precursors were directly cured into membranes of desired dimensions
      without the need for further processing steps such as melt extrusion or solvent
      casting. By employing chemical cross-linking, high proton conductivities can be
      achieved through the incorporation of significant levels of acidic groups without
      rendering the material water-soluble, which plagues commonly used non-cross
      linked polymers. Fabrication of membrane electrode assemblies (MEAs) from these
      PEMs resulted in fuel cells that outperformed those based on commercial
      materials. Moreover, these liquid precursors enabled the formation of three
      dimensional, patterned PEMs with high fidelity, micron-scale features by using
      soft lithographic/micromolding techniques. The patterned membranes provided a
      larger interfacial area between the membrane and catalyst layer than standard
      flat PEMs. MEAs composed of the patterned membranes demonstrated higher power
      densities over that of flat ones without an increase in the macroscopic area of
      the fuel cells. This can potentially miniaturize fuel cells and promote their
      application in portable devices.

PMID- 17002394
TI  - Dienamine catalysis: organocatalytic asymmetric gamma-amination of alpha,beta
      unsaturated aldehydes.
AB  - A new concept in organocatalysis is presented, the direct asymmetric gamma
      functionalization of alpha,beta-unsaturated aldehydes. We disclose that secondary
      amines can invert the usual reactivity of alpha,beta-unsaturated aldehydes,
      enabling a direct gamma-amination of the carbonyl compound using
      azodicarboxylates as the electrophilic nitrogen-source. The scope of the reaction
      is demonstrated for the enantioselective gamma-amination of different alpha,beta
      unsaturated aldehydes, giving the products in moderate to good yields and with
      high enantioselectivities up to 93% ee. Experimental investigations and DFT
      calculations indicate that the reaction might proceed as a hetero-Diels-Alder
      cycloaddition reaction. Such a mechanism can explain the "unexpected"
      stereochemical outcome of the reaction.

PMID- 17002395
TI  - A multistep oriented attachment kinetics: coarsening of ZnS nanoparticle in
      concentrated NaOH.
AB  - Crystal growth of ZnS nanoparticles during hydrothermal coarsened in 4 M NaOH
      occurs via a two-stage process. In the first stage, the primary particles grow
      into a size over hundred times of the original volume. The initial growth rate
      can be fitted by an asymptotic curve. High-resolution transmission electron
      microscope (HRTEM) data indicate that in this stage, crystal growth mainly occurs
      via a multistep crystallographically specific oriented attachment (OA). The
      higher the coarsening temperature, the earlier the first stage ends. In the
      second stage, an abrupt transition from asymptotic to square parabola growth
      kinetics occurs. The crystal growth data can be fitted by a standard Ostwald
      ripening (OR) model consistent with growth controlled by
      dissolution/precipitation of ions in solution. HRTEM data indicate that a minor
      amount of OA-based growth also occurs in the early period of the second stage. A
      new multistep OA kinetics model analogous to the reaction between molecules was
      proposed to illustrate the asymptotic growth in the first stage of coarsening.
      The effect of concentrated NaOH was discussed and proved to be the key that
      hindered the OR process, attributing to the almost exclusive pure OA-based growth
      of ZnS particles in the first stage.

PMID- 17002396
TI  - Solution 1H NMR characterization of the axial bonding of the two His in oxidized
      human cytoglobin.
AB  - Solution 1H NMR spectroscopy has been used to determine the relative strengths
      (covalency) of the two axial His-Fe bonds in paramagnetic, S = 1/2, human met
      cytoglobin. The sequence specific assignments of crucial portions of the proximal
      and distal helices, together with the magnitude of hyperfine shifts and
      paramagnetic relaxation, establish that His81 and His113, at the canonical
      positions E7 and F8 in the myoglobin fold, respectively, are ligated to the iron.
      The characterized complex (approximately 90%) in solution has protohemin oriented
      as in crystals, with the remaining approximately 10% exhibiting the hemin
      orientation rotated 180 degrees about the alpha-, gamma-meso axis. No evidence
      could be obtained for any five-coordinate complex (<1%) in equilibrium with the
      six-coordinate complexes. Extensive sequence-specific assignments on other
      dipolar shifted helical fragments and loops, together with available alternate
      crystal coordinates for the complex, allowed the robust determination of the
      orientation and anisotropies of the paramagnetic susceptibility tensor. The tilt
      of the major axis is controlled by the His-Fe-His vector, and the rhombic axes
      are controlled by the mean of the imidazole orientations for the two His. The
      anisotropy of the paramagnetic susceptibility tensor allowed the quantitative
      factoring of the hyperfine shifts for the two axial His to reveal an
      indistinguishable pattern and magnitudes of the contact shifts or pi spin
      densities, and hence, indistinguishable Fe-imidazole covalency for both Fe-His
      bonds.

PMID- 17002398
TI  - DFT studies on the mechanism of allylative dearomatization catalyzed by
      palladium.
AB  - The reaction mechanism of the Pd-catalyzed benzyl/allyl coupling of benzyl
      chloride with allyltributylstannan, resulting in the dearomatization of the
      benzyl group, was studied using density functional theory calculations at the
      B3LYP level. The calculations indicate that the intermediate (eta(3)
      benzyl)(eta(1)-allyl)Pd(PH(3)) is responsible for the formation of the
      kinetically favored dearomatic product. Reductive elimination of the dearomatic
      product from the intermediate occurs by coupling the C-3 terminus of the eta(1)
      allyl ligand and the para-carbon of the eta(3)-benzyl ligand in (eta(3)
      benzyl)(eta(1)-allyl)Pd(PH(3)). For comparison, various C-C coupling reaction
      pathways have also been examined.

PMID- 17002397
TI  - High-throughput sequence determination of cyclic peptide library members by
      partial Edman degradation/mass spectrometry.
AB  - Cyclic peptides provide attractive lead compounds for drug discovery and
      excellent molecular probes in biomedical research. Large combinatorial libraries
      of cyclic peptides can now be routinely synthesized by the split-and-pool method
      and screened against biological targets. However, post-screening sequence
      determination of hit peptides has been problematic. In this report, a high
      throughput method for the sequence determination of cyclic peptide library
      members has been developed. TentaGel microbeads (90 mum) were spatially
      segregated into outer and inner layers; cyclic peptides were displayed on the
      bead surface, whereas the inner core of each bead contained the corresponding
      linear peptide as the encoding sequence. After screening of the cyclic peptide
      library against a macromolecular target, the identity of hit peptides was
      determined by sequencing the linear encoding peptides inside the bead using a
      partial Edman degradation/mass spectrometry method. On-bead screening of an
      octapeptide library (theoretical diversity of 160 000) identified cyclic peptides
      that bind to streptavidin. A 400-member library of tyrocidine A analogues was
      synthesized on TentaGel macrobeads and solution-phase screening of the library
      directly against bacterial cells identified a tyrocidine analogue of improved
      antibacterial activity. Our results demonstrate that the new method for cyclic
      peptide sequence determination is reliable, operationally simple, rapid, and
      inexpensive and should greatly expand the utility of cyclic peptides in
      biomedical research.

PMID- 17002399
TI  - Hafnocene catalysts for selective propylene oligomerization: efficient synthesis
      of 4-methyl-1-pentene by beta-methyl transfer.
AB  - A series of hafnocene complexes (eta5-C5Me4R1)(eta5-C5Me4R2)HfCl2 with [R1, R2] =
      [H, H] (1), [Me, H] (2), [Me, Me] (3), [Et, Me] (4), [(i)Pr, Me] (5), [SiMe(3),
      Me] (6), [(t)Bu, Me] (7), [(n)Bu, Me] (8), [(i)Bu, Me] (9), [Et, Et] (10),
      [(n)Bu, (n)Bu] (11), [(i)Bu, (i)Bu] (12) was tested as catalyst precursors for
      propylene oligomerization. Upon activation with methylaluminoxane or
      [Ph(3)C][B(C(6)F(5))(4)]/Al(i)Bu(3), complexes 2-4 and 8-12 catalyzed the
      dimerization of propylene to produce 4-methyl-1-pentene with selectivities
      ranging from 23.9 to 61.6 wt % in the product mixture. The selectivity was
      dependent on the nature of the substituents R(1) and R(2), with the highest value
      found for (eta5-C5Me4(i)Bu)2HfCl2 (12). Rapid deactivation was observed for 5-7,
      whereas (eta5-C5Me4H)2HfCl2 (1) polymerized propylene. 4-Methyl-1-pentene is
      proposed to form by repeated 1,2-insertion of propylene into the hafnocene methyl
      cation, followed by selective beta-methyl elimination. Detailed analysis of the
      byproduct distribution (isobutene, 1-pentene, 2-methyl-1-pentene, 2,4-dimethyl-1
      pentene, 4-methyl-1-heptene, 4,6-dimethyl-1-heptene), determined by gas
      chromatography, was performed with the aid of a stochastic simulation involving
      rate constants for the propagation by insertion, beta-hydride elimination, and
      beta-methyl elimination. The rate of termination is dependent on the structure of
      the growing chain of the active species as well as on the bulkiness of the
      cyclopentadienyl ligands. The selectivity highly depends on the reaction
      conditions (pressure, temperature, concentration of methylaluminoxane). The rates
      of beta-methyl elimination leading to 4-methyl-1-pentene were proportional to
      propylene pressure for 2-4 and 8-10 but practically independent from propylene
      pressure for the sterically bulkier derivatives 11-12.

PMID- 17002401
TI  - Development and use of an attenuated total reflectance/fourier transform infrared
      (ATR/FT-IR) spectral database to identify foreign matter in cotton.
AB  - The presence of foreign matter in cotton seriously affects the cotton grade and
      thus the price per bale paid by the spinner to the grower, the efficiency of the
      spinning and ginning operations, and the quality of the final woven product.
      Rapid identification of the nature of the extraneous matter in cotton at each
      stage of cleaning and processing is necessary to permit actions to eliminate or
      reduce its presence and improve efficiency and quality. Although several
      instruments are being successfully employed for the measurement of contamination
      in cotton fibers based on particle size/weight, no commercial instrument is
      capable of accurate qualitative identification of contaminants. To this end,
      ATR/FT-IR spectra of retrieved foreign matter were collected and subsequently
      rapidly matched to an authentic spectrum in a spectral database. The database
      includes contaminants typically classified as "trash", cotton plant parts (hull,
      shale, seed-coat fragments, bract, cacyx, leaf, bark, sticks, and stems) and
      grass plant parts (leaf and stem); "foreign objects and materials", synthetic
      materials (plastic bags, film, rubber, bale wrapping and strapping); organic
      materials (other fibers, yarns, paper, feathers, and leather); plus entomological
      and physiological sugars and inorganic materials (sand and rust). The spectral
      matching resulted in consistently high-score identification of the foreign matter
      based on chemical composition, irrespective of its particle size. The method is
      envisioned to be employed with stand-alone rugged infrared instrumentation to
      provide specific identification of extraneous materials in cotton as opposed to
      only general classification of the type by particle size or shape.

PMID- 17002402
TI  - Investigation of sample treatment steps for the analysis of polycyclic aromatic
      hydrocarbons in ground coffee.
AB  - Sample treatment procedures were tested for the determination of polycyclic
      aromatic hydrocarbons (PAHs) in ground coffee. Pressurized liquid extraction
      (PLE), under different conditions, was combined with several cleanup methods,
      namely in situ purification, C18-silica solid-phase extraction (SPE), silica SPE,
      acid digestion, and alkaline saponification. Soxhlet extraction and direct
      alkaline saponification were also tested. Best results were obtained using PLE
      with hexane/acetone 50:50 (v/v) under 150 degrees C. Alkaline saponification
      followed by cyclohexane extraction and silica SPE was required to eliminate
      interferent compounds. Finally, 11 PAHs could be quantified in ground coffee with
      limits of detection in the range of 0.11-0.18 microg kg(-1). Application to
      ground Arabica coffee lots from Colombia revealed the presence of several PAHs,
      giving an overall toxicity equivalence in the range of 0.16-0.87 microg kg(-1).
      PAH identification was performed using both high-performance liquid
      chromatography-diode array detection and gas chromatography coupled to mass
      spectrometry.

PMID- 17002403
TI  - HPLC quantification of sphingolipids in soybeans with modified palmitate content.
AB  - Efficient separation and accurate quantification of sphingolipids (SL) are
      important for studying SL concentrations and biological functions. The objectives
      of this study were to develop effective methods for the separation and
      quantification of SL and to determine the relationship between palmitate and SL
      contents of mature soybean seeds. Methods using column chromatography and high
      performance liquid chromatography-evaporative light scattering detector (HPLC
      ELSD) were developed to separate and quantify glucosylceramide (GlcCer) and
      ceramide (Cer) in 15 soybeans lines in which palmitate content ranged from 3.7 to
      40.7%. There were significant differences among the lines for GlcCer (83.4-397.6
      nmol/g) and major Cer contents (8.4-20.7 nmol/g) on a dry weight basis. The
      correlations of palmitate content with GlcCer and Cer concentrations were not
      significant. The results indicated that the palmitate content of soybean seed did
      not affect their GlcCer and Cer contents. Genetic factors other than those that
      control palmitate content seemed to be responsible for the variation among
      soybean lines for GlcCer and Cer contents.

PMID- 17002404
TI  - High-throughput relative DPPH radical scavenging capacity assay.
AB  - A high-throughput relative 2,2-diphenyl-1-picryhydrazyl (DPPH) radical scavenging
      capacity (RDSC) assay was developed and validated in the present study. This RDSC
      assay is easy to perform and has acceptable accuracy (90-110% recovery),
      precision [3.9-7.0% pooled relative standard deviation (RSD)], and
      reproducibility (2.2 and 3.5% interday and intraday RSD). This assay reports the
      RDSC values for antioxidant samples, which make it possible to compare the DPPH
      radical scavenging capacities of antioxidants determined in different
      laboratories. The RDSC assay may be conducted in aqueous alcohol and acetone for
      hydrophilic antioxidants or in the organic solvents for lipophilic antioxidants
      without solubilizing agents, which makes it possible to directly compare the
      radical scavenging capacities of hydrophilic and lipophilic antioxidants. In
      addition, the high-throughput RDSC assay could be utilized for EC50 value
      estimation. The high-throughput RDSC assay may be used for screening and
      investigating potential natural antioxidants.

PMID- 17002405
TI  - Measurement of soluble solids contents and pH in orange juice using chemometrics
      and vis-NIRS.
AB  - The potential of visible and near-infrared reflectance spectroscopy (vis-NIRS)
      was investigated for its ability to nondestructively detect soluble solids
      contents (SSC) and pH in orange juices. A total of 104 orange juice samples were
      used for vis-NIRS at 325-1075 nm using a field spectroradiometer. Wavelet packet
      transform, standard normal variate transformation (SNV), and Savitzky-Golay first
      derivative transformation were applied for the preprocessing of spectral data.
      The chemometrics of partial least-squares (PLS) regression analysis was performed
      on the processed spectral data. The evaluation of SSC and pH in orange juices by
      PLS regression with SNV showed the highest accuracy of the three preprocessing
      methods. The correlation coefficient (r), standard error of prediction, and the
      root-mean-square error of prediction for SSC were 0.98, 0.68, and 0.73,
      respectively, whereas those values for pH were 0.96, 0.06, and 0.06,
      respectively. The "fingerprint" representing features of orange juices or
      reflecting sensitivity to some elements at a certain band was proposed on the
      basis of regression coefficients. It is very useful in the field of food
      chemistry and further research on other materials. It is concluded that the vis
      NIRS technique combined with chemometrics is promising for the fast and
      nondestructive detection of chemical components in orange juices or other
      materials.

PMID- 17002406
TI  - Pro-oxidant activity of oleuropein determined in vitro by electron spin resonance
      spin-trapping methodology.
AB  - In this work, the pro-oxidant behavior of oleuropein (OLP, 1) is characterized in
      a Fenton-like experiment by means of ESR spectroscopy using the spin trap system
      DMSO and 4-(pyridyl-1-oxide)-N-tert-butyl nitrone (POBN) in phosphate buffer (PB)
      solution. Ferrous ions in the absence of hydrogen peroxide cause the formation of
      the stable nitroxide species 4 and 5 through the intermediate perferryl species.
      OLP displays its antioxidant activity in vitro blocking the oxidation path that
      leads to methoxyl radicals hence to the formation of the stable radical species
      5. The role of the catechol moiety was proved when the perferryl experiments were
      repeated in the presence of the dimethylated oleuropein homologue (OLP-Met2, 2).
      The dual behavior of oleuropein, similar to that ascertained for other catechol
      and non-catechol natural active species, should provide warnings for its use as
      nutraceutical or as drug with manifold healing effects.

PMID- 17002407
TI  - Simultaneous determination of ethidimuron, methabenzthiazuron, and their two
      major degradation products in soil.
AB  - An analytical method has been developed for the quantification of two herbicides
      (ethidimuron and methabenzthiazuron) and their two main soil derivatives. This
      method involves fluidized-bed extraction (FBE) prior to cleanup and analysis by
      reverse-phase liquid chromatography with UV detection at 282 nm. FBE conditions
      were established to provide efficient extraction without degradation of the four
      analytes. (14)C-labeled compounds were used for the optimization of extraction
      and purification steps and for the determination of related efficiencies.
      Extraction was optimal using a fexIKA extractor operating at 110 degrees C for
      three cycles (total time = 95 min) with 75 g of soil and 150 mL of a 60:40 v/v
      acetone/water mixture. Extracts were further purified on a 500 mg silica SPE
      cartridge. Separation was performed on a C18 Purosphere column (250 mm x 4 mm
      i.d.), at 0.8 mL min(-1) and 30 degrees C with an elution gradient made up of
      phosphoric acid aqueous solution (pH 2.2) and acetonitrile. Calibration curves
      were found to be linear in the 0.5-50 mg L(-1) concentration range. Besides
      freshly spiked soil samples, method validation included the analysis of samples
      with aged residues. Recovery values, determined from spiked samples, were close
      to 100%. Limits of detection ranged between 2 and 3 microg kg(-1) of dry soil and
      limits of quantification between 8 and 10 microg kg(-1) of dry soil. An attempt
      to improve these performances by using fluorescence detection following
      postcolumn derivatization by orthophthalaldehyde-mercaptoethanol reagent was
      unsuccessful.

PMID- 17002408
TI  - HPLC-UV method for nicotine, strychnine, and aconitine in dairy products.
AB  - The toxic nitrogen alkaloids nicotine, strychnine, and aconitine were quantitated
      in whole milk, skim milk, and cream using solid-phase extraction cleanup and HPLC
      UV with dual wavelength detection. Samples were extracted in McIlvaine's buffer
      with EDTA and then partitioned with aqueous acetonitrile and hexane. The aqueous
      phase was concentrated and passed through an OASIS HLB column. The column was
      eluted with methylene chloride/ammonium hydroxide, 1 mL/1 microL, v/v. The eluent
      was acidified with hydrochloric acid and evaporated. The sample was diluted for
      HPLC with acetonitrile/phosphate buffer pH 7.4. Chromatography was performed on
      an Xterra RP-18 column using a gradient of acetonitrile and ammonium bicarbonate
      buffer at pH 9.8. Nicotine and strychnine were monitored at 260 nm; aconitine was
      monitored at 232 nm. Calibration curves were generated from external standards in
      the range 0.2-10 microg/mL using 1/x weighting. Mean recoveries in whole milk
      spiked between 0.1 and 10 ppm were the following: nicotine 89.2%, strychnine
      75.7%, and aconitine 85.1%. Mean recoveries in skim milk spiked between 0.1 and
      10 ppm were the following: nicotine 72.1%, strychnine 78.2%, and aconitine 82.9%.
      Mean recoveries in cream spiked between 0.2 and 20 ppm were the following:
      nicotine 87.9%, strychnine 76.9%, and aconitine 82.0%. Relative standard
      deviations of recovery were less than 20% in each case.

PMID- 17002409
TI  - Authentication of coffee by means of PCR-RFLP analysis and lab-on-a-chip
      capillary electrophoresis.
AB  - Coffee is one of the most important world food commodities, commercial trade
      consisting almost entirely of Arabica and Robusta varieties. The former is
      considered to be of superior quality and thus attracts a premium price. Methods
      to differentiate these coffee species could prove to be beneficial for the
      detection of either deliberate or accidental adulteration. This study describes a
      molecular genetics approach to differentiate Arabica and Robusta coffee beans.
      This employs a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism
      to monitor a single nucleotide polymorphism within the chloroplastic genome.
      Samples were analyzed with a lab-on-a-chip capillary electrophoresis system.
      Coffee powder mixtures were analyzed with this technique, displaying a 5% limit
      of detection. The plastid copy number was found to be relatively constant across
      a wide range of bean samples, suggesting that this methodology can also be
      employed for the quantification of any adulteration of Arabica with Robusta
      beans.

PMID- 17002410
TI  - A strategy for annotating the human milk glycome.
AB  - Oligosaccharides in human milk represent a group of bioactive molecules that have
      evolved to be an abundant and diverse component of human milk, even though they
      have no direct nutritive value to the infant. A recent hypothesis proposes that
      they could be substrates for the development of the intestinal microflora and the
      mucosal immune system. The inability to determine the exact composition of these
      oligosaccharides limits research and the ability to understand their biological
      functions. Oligosaccharides isolated from the lipids and proteins of individual
      human milk samples were analyzed by a combination of techniques including
      microchip liquid chromatography mass spectrometry (HPLC-Chip/MS) and matrix
      assisted laser desorption/ionization Fourier transform ion cyclotron resonance
      mass spectrometry (MALDI-FT ICR MS). Accurate mass measurements obtained using an
      orthogonal time-of-flight (o-TOF) mass spectrometry provided oligosaccharide
      composition for approximately 200 individual molecular species. Comparison of
      HPLC-Chip/MS profiles from five different women revealed variations in milk
      oligosaccharide compositions. HPLC-Chip/MS profiling provides a method for
      routinely identifying milk oligosaccharides. Tandem MS in combination with
      exoglycosidase digestion provides unambiguous differentiation of structural
      isomers.

PMID- 17002411
TI  - Monomers of condensed tannins affect the larval exsheathment of parasitic
      nematodes of ruminants.
AB  - The current control of parasitic nematodes in small ruminants relies on the use
      of chemical anthelmintics, but the development of resistance requires research in
      alternatives. Bioactive plants represent one of those solutions. Previous results
      suggest that plants rich in condensed tannins (CTs) might have direct
      anthelmintic effects. However, the relationships between the biochemistry of
      active compounds and the mechanisms of action remain to be elucidated. Therefore,
      this study examined in vitro the effects of different CT monomers on the
      exsheathment of infective larvae for two nematode species. Monomers of
      prodelphinidins were more potent inhibitors of exsheathment than those of
      procyanidins. More severe inhibition was also found with galloyl derivatives.
      These results suggest that the number of free hydroxy groups of CT monomers is a
      key factor in interactions with parasite larvae. Comparison of effects between
      the two nematodes suggests different susceptibility to monomers depending on
      species, which might be related to the protein composition of sheaths.

PMID- 17002412
TI  - Survey of grapevine Vitis vinifera stem polyphenols by liquid chromatography
      diode array detection-tandem mass spectrometry.
AB  - Grapes and red wine prepared from Vitis vinifera L. contain a variety of
      polyphenols. Some information is available about the polyphenols of the seeds and
      leaves of grapevine, but considerably less is known about the polyphenols of
      woody stems. In this paper, we describe the results of a study of polyphenolic
      compounds in grapevine stems. We demonstrate how a combination of reversed phase
      high-performance liquid chromatography with ultraviolet-diode array detection and
      electrospray ionization-tandem mass spectrometry ion-trap detection enables
      characterization of a phytochemical mixture of considerable complexity. As the
      polyphenol source, the stems of three frost-hardy grapevine varieties [Hasaine
      (Hasansky) sladki, Zilga, and Yubilei Novgoroda] were used. The main group of
      methanol-extractable polyphenols of stems consists of trans-resveratrol and its
      derivatives including oligomers and glucosides. As minor components of the
      extract, stilbenoid piceatannol as well as a number of nonstilbenoid polyphenols,
      mostly flavan-3-ols and phenolic acids glucosides, were determined. The total
      polyphenol content of the grapevine stems depends on the variety, whereby the
      stems of cultivar Yubilei Novgoroda with white grapes contain significantly less
      of both groups of polyphenols.

PMID- 17002413
TI  - Heat and pH effects on the conjugated forms of genistin and daidzin isoflavones.
AB  - Isoflavones occur primarily as glycosides (namely, malonyl-, acetyl-, and non
      conjugated beta-glycosides) and a small percentage as the bioactive aglycon. The
      different chemical structures of isoflavones can dictate their stability during
      processing. Therefore, our objective was to determine the effects of pH and
      thermal treatments on conjugated isoflavones with regard to interconversions and
      loss. Conjugated daidzin and genistin were heated at 25, 80, and 100 degrees C
      under neutral, acidic, and basic conditions. Changes in isoflavone derivatives
      were monitored using high-performance liquid chromatography. Along with
      interconversions, considerable loss in total known isoflavone derivatives was
      noted for each isoflavone, especially under elevated pH and temperature. The
      malonylglycosides showed more stability than acetylglycosides, especially under
      acidic conditions. Overall, loss in isoflavone derivatives was significantly
      higher for daidzin than for genistin glycoside forms. Our results highlighted the
      significance of chemical structure with regard to stability, which is a key
      factor in determining soy processing conditions.

PMID- 17002414
TI  - Diallyl disulfide increases CDKN1A promoter-associated histone acetylation in
      human colon tumor cell lines.
AB  - Diallyl disulfide (DADS) is an organosulfur compound from garlic, which inhibits
      colon tumor cell proliferation. In a previous study, we have shown that in Caco-2
      and HT-29 cells DADS (200 microM) increases global histone acetylation, CDKN1A
      mRNA, and p21(waf1) protein levels and induces G2/M cell cycle arrest. These
      results suggested that DADS could inhibit cell proliferation through at least in
      part a transcriptional activation of CDKN1A expression involving histone
      acetylation. In this study, using chromatin immunoprecipitation assays, we
      demonstrate that in Caco-2 and HT-29 cells histone H4 and/or H3 acetylation is
      increased within CDKN1A promoter after 3 and 6 h treatments with DADS. These
      results strongly suggest that histone acetylation, a molecular mechanism
      implicated in the regulation of gene expression, could account for the induction
      of CDKN1A expression and the antiproliferating effects of DADS in colon tumor
      cells.

PMID- 17002415
TI  - New constituents of sweet Capsicum annuum L. fruits and evaluation of their
      biological activity.
AB  - Four new acyclic diterpene glycosides named capsianosides (1-4), together with 12
      known compounds, were isolated from the fresh sweet pepper fruits of Capsicum
      annuum L., a plant used as a vegetable food, spice, and external medicine. The
      chemical structures of new natural compounds, as well as their absolute
      configurations, were established by means of spectroscopic data including
      infrared, high-resolution mass spectrometry, and one- and two-dimensional nuclear
      magnetic resonance and by chemical derivatization. The known capsidiol (11)
      showed bacteriostatic properties in vitro against Helicobacter pylori with a
      minimum inhibitory concentration (MIC) of 200 microg/mL when compared with the
      commercial drug metronidazole (MIC, 250 microg/mL). Some purified components were
      also tested for their antioxidant activities.

PMID- 17002416
TI  - The antifungal activity of widdrol and its biotransformation by Colletotrichum
      gloeosporioides (penz.) Penz. & Sacc. and Botrytis cinerea Pers.: Fr.
AB  - Widdrol (1) was tested against the necrotrophic plant pathogens Botrytis cinerea
      and Colletotrichum gloeosporioides. While 1 was found to be inactive against C.
      gloeosporioides, it showed a selective and effective control of B. cinerea,
      significantly inhibiting the mycelial growth of the fungus at concentrations of
      100 ppm and above. In addition, the biotransformation of 1 by both fungi was
      studied. Incubation with C. gloeosporioides and B. cinerea afforded four and one
      biotransformation products (2-6), respectively. Biotransformation with C.
      gloeosporioides was highly regioselective, yielding for the most part oxidation
      products at C-10: 10-oxowiddrol (2), 10beta-hydroxywiddrol (3), 10alpha
      hydroxywiddrol (4), and 14alpha-hydroxywiddrol (5). The structures of all
      products were determined on the basis of their spectroscopic data, including
      coupling constants, two-dimensional NMR analysis (heteronuclear multiple quantum
      coherence, heteronuclear multiple bond correlation, and nuclear Overhauser
      enhancement spectroscopy), and nuclear Overhauser effect. The biotransformation
      products were then tested against B. cinerea and found to be inactive. These
      results shed further light on the structural modifications, which may be
      necessary to develop selective fungal control agents against B. cinerea.

PMID- 17002417
TI  - Bioactivity of anacardic acid against colorado potato beetle (Leptinotarsa
      decemlineata) larvae.
AB  - Anacardic acid (2-hydroxy-6-alkylbenzoic acid) produced and secreted from
      glandular trichomes of zonal geranium (Pelargonium x hortorum; Geraniaceae
      family) provides resistance to small pests (aphids and spider mites). To assess
      the potential bioactivity of anacardic acid against larger insect pests and to
      determine if an alternate mode of application (ingestion rather than the topical
      application) could impart resistance to pests, the effects of anacardic acid
      consumption on the development of Colorado potato beetle larvae were tested.
      Analysis of dose-response curves indicated a significant effect on weight gain
      and mortality. Assessment of food preference (treated versus untreated) indicated
      larvae avoid food containing anacardic acid and have a lower feeding rate on food
      containing anacardic acid. On the basis of these results, it is suggested that
      anacardic acid, applied as a chemical spray or through bioengineering production
      in crop plants, may provide a new tool in the arsenal to minimize damage to
      plants caused by pests.

PMID- 17002418
TI  - High-performance liquid chromatography analysis of black currant (Ribes nigrum
      L.) fruit phenolics grown either conventionally or organically.
AB  - Black currants (Ribes nigrum L.) contain a diverse range of phenolics and possess
      a high antioxidant activity, which makes them an interesting target for the
      functional food industry. In this study, phenolic profiles of organically and
      conventionally grown black currant fruits, collected from commercial farms within
      a climatically similar area, were compared. Compounds were identified using
      UV/vis and mass spectroscopy techniques and quantified with high-performance
      liquid chromatography equipped with UV/vis detection. Several different
      conjugates of hydroxycinnamic acids, flavonols, and anthocyanins were quantified.
      Statistically significant differences between farms were found for almost all
      compounds. Differences between the highest and the lowest measured values of
      major phenolic compounds of different phenolic classes ranged from 24 to 77%.
      Principal component analysis quite effectively separated farms from each other
      but did not cluster them according to cultivation technique. Thus, it was
      concluded that the biochemical quality of organically grown black currant fruits
      does not differ from those grown conventionally.

PMID- 17002419
TI  - Phenolic acids are absorbed from the rat stomach with different absorption rates.
AB  - The intestinal absorption characteristics of phenolic acids (PAs) have been
      elucidated in terms of their affinity for the monocarboxylic acid transporter
      (MCT). Recently, the involvement of the stomach has been implicated in the
      absorption of polyphenols. The present work demonstrates that the gastric
      absorption efficiency of each PA is apparently different between various PAs.
      Various PAs with different affinities for MCT were administered (2.25 mumol) to
      rat stomach, and then the plasma concentration of the PA was measured. The plasma
      concentration of ferulic acid (FA) peaked 5 min after administration in the
      stomach. At 5 min after administration, the plasma concentration of each PA
      increased in the order: gallic acid = chlorogenic acid < caffeic acid < p
      coumaric acid = FA. This order matches their respective affinity for MCT in Caco
      2 cells, which we have demonstrated in previous studies. These results indicated
      that MCT might be involved in the gastric absorption of PAs, similar to the
      intestinal absorption.

PMID- 17002420
TI  - Functional components in soybean cake and their effects on antioxidant activity.
AB  - The antioxidant activities of four fractions of isoflavones from soybean cake
      were evaluated and compared with those of ISO-1 and ISO-2 fractions, five
      isoflavone standards, and mixtures of two or four isoflavone standards, as well
      as four commercial antioxidants, using DPPH, TEAC, reducing power, metal ion
      chelating, conjugated diene, and TBARS assays. Both malonylglucoside and
      glucoside fractions were isolated using preparative chromatography with Diaion HP
      20 as adsorbent, whereas acetylglucoside and aglycone fractions were separated
      with silica gel as adsorbent. The other two fractions, ISO-1 and ISO-2, were
      soybean cake extracts containing 12 isoflavones for the former and a combination
      of 4 fractions for the latter. Both acetylglucoside and ISO-1 fractions exhibited
      the highest efficiency in scavenging DPPH free radicals, whereas all six
      fractions were effective in inhibiting conjugated diene formation. However, a low
      reducing power was observed for all six fractions and isoflavone standards. The
      aglycone fraction and genistein standard showed a pronounced increase of TEAC
      value and a moderate decrease of TBARs value. For chelating metal ions, both ISO
      1 and ISO-2 fractions were the most efficient. Overall, the isoflavone fractions
      showed a better antioxidant activity than the isoflavone standards, probably
      caused by the presence of some other functional components such as saponin,
      flavonoid, and phenolic compounds in soybean cake.

PMID- 17002421
TI  - Analytical discrimination of poisonous and nonpoisonous chemotypes of giant
      fennel (Ferula communis L.) through their biologically active and volatile
      fractions.
AB  - Giant fennel (Ferula communis L.) from Sardinia is characterized by two
      chemotypes with different biological activities. One chemotype is poisonous, due
      to prenylcoumarins, and responsible for ferulosis, which mainly affects sheep and
      goats, cattle, and horses; the other chemotype is nonpoisonous and contains
      daucane esters. The two chemotypes cannot be distinguished botanically. High
      performance liquid chromatography-diode array-ultraviolet detection-mass
      spectrometry (HPLC-DAD-UV-MS) analysis of the composition of the fractions
      containing the biologically active metabolites and of the volatile fractions, by
      gas chromatography-mass spectrometry (GC-MS), of both essential oil and headspace
      sampled by headspace solid-phase microextraction (HS-SPME) are here shown to be
      effective in discriminating the poisonous and nonpoisonous chemotypes. HS-SPME
      with CAR/PDMS/DVB in combination with GC-MS has also been found to be a
      successful, fully automated one-step method for rapid and unequivocal
      discrimination of the two chemotypes, using aristolene and allohedycaryol as
      markers of the poisonous and nonpoisonous chemotypes, respectively.

PMID- 17002422
TI  - o-Orsellinaldehyde from the submerged culture of the edible mushroom Grifola
      frondosa exhibits selective cytotoxic effect against Hep 3B cells through
      apoptosis.
AB  - The tumoricidal activity of a bioactive metabolite produced by submerged culture
      in a 2.1-L airlift fermentor of Grifola frondosa NTUS was investigated. After 14
      days of cultivation, ethyl acetate extracts from the supernatant of culture broth
      (EES) were analyzed by cell viability assay. The IC50 of EES for cytotoxicity
      against human carcinoma cells (Hep 3B, Hep G2, HeLa, CL1-1) and normal human lung
      fibroblast MRC-5 was 78.4, 52.7, 77.6, 71.0, and 233.3 microg/mL, respectively.
      EES was further fractionated and a main cytotoxic compound, HE-5-5, was obtained.
      The IC50 of HE-5-5 based on the cell viability of Hep 3B and MRC-5 cells was 3.6
      and 33.1 microg/mL, respectively. Thus, HE-5-5 showed a selective cytotoxic
      effect against Hep 3B cells and MRC-5. According to the UV, MS, and NMR data, HE
      5-5 was identified as o-orsellinaldehyde. A DNA fragmentation assay together with
      the presence of a significant sub-G1 peak by flow cytometry suggested that o
      orsellinaldehyde might mediate its cytotoxicity through apoptosis.

PMID- 17002423
TI  - New lignans from the perisperm of Sesamum indicum.
AB  - A procedure, based on XAD-4 adsorption resin, which permits the obtainment of
      enriched polyphenolic extracts from Sesamum indicum perisperm (coat) has been
      developed. Chemical analysis of the obtained extracts led to the identification
      of 16 lignans. Among them, two new lignans, (+)-saminol and (+)-episesaminone-9-O
      beta-D-sophoroside, have been isolated. Additionally, the relative
      stereochemistry of (-)-sesamolactol, previously reported as todolactol A epimer,
      has been unequivocally defined using X-ray crystallography. The structures of all
      new compounds were determined by spectroscopic methods, mainly by the concerted
      application of 1D and 2D NMR techniques (HMQC, HMBC, and NOESY) and mass
      spectroscopy.

PMID- 17002424
TI  - Optimization of extraction of phenolic compounds from flax shives by pressurized
      low-polarity water.
AB  - Pressurized low-polarity water (PLPW) extraction of phenolic compounds from flax
      shive was investigated using statistically based optimization and the "one-factor
      at-a-time" method. Extraction variables examined using central composite design
      (CCD) included temperature, flow rate, and NaOH concentration of the extracting
      water. Extraction of phenolic compounds including p-hydroxybenzaldehyde, vanillic
      acid, syringic acid, vanillin, acetovanillone, and feruric acid was affected by
      temperature and NaOH concentration; and extraction of all phenolic compounds,
      except ferulic acid, increased with temperature and NaOH concentration of the
      extracting water. Flow rate had little effect on concentration of phenolic
      compounds at equilibrium, but the extraction rate at the early phase was higher
      for higher flow rates. The mechanism of PLPW extraction of flax shive phenolics
      was also investigated using a two-site kinetic model and a thermodynamic model.
      To determine the extraction mechanism, flow rate was varied from 0.3 to 4.0
      mL/min while temperature and NaOH concentration were fixed at 180 degrees C and
      0.47 M, respectively. The flow rate tests showed the extraction rates of total
      phenolic (TP) compounds increased with flow rate and can be described by a
      thermodynamic model. The results from the thermodynamic model demonstrated that a
      K(D) value of 30 agreed with the experimental data in the flow rate range of 0.3
      4.0 mL/min. When the effect of the three independent variables was evaluated
      simultaneously using CCD, a maximum TP concentration of 5.8 g/kg of dry flax
      shive (DFS) was predicted from the combination of a high temperature (230.5
      degrees C), a high initial concentration of NaOH (0.63 M), and a low flow rate
      (0.7 mL/min). Maximum TP concentration of 5.7 g/kg of DFS was obtained from
      extraction conditions of 180 degrees C, 0.3 or 0.5 mL/min, and 0.47 M NaOH at
      equilibrium. A second-order regression model generated by CCD predicted a maximum
      TP concentration of 5.8 g/kg of DFS under the same extraction conditions, which
      is well matched with the results from experimental data.

PMID- 17002425
TI  - An efficient method for extraction of astaxanthin from green alga Haematococcus
      pluvialis.
AB  - Haematococcus pluvialis is one of the potent organisms for production of
      astaxanthin, a high value ketocarotenoid. Astaxanthin is accumulated in thick
      walled cyst cells of Haematococcus. The thick cell wall is made up of
      sporopollenin-like material, algaenan, which hinders solvent extraction of
      astaxanthin. In the present study, an improved method for extraction of
      astaxanthin without homogenization of cells is reported. Extractability of
      astaxanthin from cyst cells was evaluated by treating cells with various solvents
      and pretreating the cells with organic and mineral acids at 70 degrees C followed
      by acetone extraction. Hydrochloric acid treatment facilitated 86-94%
      extractability of astaxanthin. Treatment time, temperature, and concentration of
      the acid were found to be critical factors for maximum extractability. The
      treatment did not affect the astaxanthin ester profile and the treated cells can
      be preserved until further use.

PMID- 17002426
TI  - Soybean glycinin subunits: Characterization of physicochemical and adhesion
      properties.
AB  - Soybean proteins have shown great potential for applications as renewable and
      environmentally friendly adhesives. The objective of this work was to study
      physicochemical and adhesion properties of soy glycinin subunits. Soybean
      glycinin was extracted from soybean flour and then fractionated into acidic and
      basic subunits with an estimated purity of 90 and 85%, respectively. Amino acid
      composition of glycinin subunits was determined. The high hydrophobic amino acid
      content is a major contributor to the solubility behavior and water resistance of
      the basic subunits. Acidic subunits and glycinin had similar solubility profiles,
      showing more than 80% solubility at pH 2.0-4.0 or 6.5-12.0, whereas basic
      subunits had considerably lower solubility with the minimum at pH 4.5-8.0.
      Thermal analysis using a differential scanning calorimeter suggested that basic
      subunits form new oligomeric structures with higher thermal stability than
      glycinin but no highly ordered structures present in isolated acidic subunits.
      The wet strength of basic subunits was 160% more than that of acidic subunits
      prepared at their respective isoelectric points (pI) and cured at 130 degrees C.
      Both pH and the curing temperature significantly affected adhesive performance.
      High-adhesion water resistance was usually observed for adhesives from protein
      prepared at their pI values and cured at elevated temperatures. Basic subunits
      are responsible for the water resistance of glycinin and are a good starting
      material for the development of water-resistant adhesives.

PMID- 17002427
TI  - Biobased grease with improved oxidation performance for industrial application.
AB  - Vegetable oils have significant potential as a base fluid and a substitute for
      mineral oil for grease formulation. This paper describes the preparation of
      biobased grease with high oxidative stability and a composition useful for
      industrial, agriculture/farming equipment, and forestry applications. The process
      utilizes more oxidatively stable epoxy vegetable oils as the base fluid, metal
      soap thickener, and several specialty chemicals identified to address specific
      applications. Performance characteristics of greases used for industrial and
      automotive applications are largely dependent on the hardness and the oxidative
      stability of grease. Grease hardness was determined using standard test methods,
      and their oxidative stabilities were determined using pressurized differential
      scanning calorimetry and rotary bomb oxidation tests. Wear data were generated
      using standard test methods in a four-ball test geometry. Results indicate that
      grease developed with this method can deliver at par or better performance
      properties (effective lubrication, wear protection, corrosion resistance,
      friction reduction, heat removal, etc.) than existing mineral oil-based greases
      currently used in similar trades. Therefore, developed greases can be a good
      substitute for mineral oil-based greases in industrial, agriculture, forestry,
      and marine applications.

PMID- 17002428
TI  - Preparation of monoclonal antibody against celangulin V and immunolocalization of
      receptor in the oriental armyworm, Mythimna separata walker (Lepidoptera:
      Noctuidae).
AB  - The botanical insecticide celangulin V (CA-V) is an insect digestive poison
      acting on midgut tissue of the target insect larvae. With the aim of localizing
      the receptor enacted by CA-V, monoclonal antibodies (MAbs) specific to the
      compound were developed. A hapten was synthesized by introducing a succinoyl into
      the CA-V structure and conjugated with three carrier proteins. From mice
      immunized with one conjugate, three MAbs were obtained with a potential capacity
      of detecting protein-bound residue forms of CA-V in the biological tissues. The
      oriental armyworm larvae ingested CA-V were examined by the technique of immuno
      electron-microscopy (IEM) using the anti-CA-V MAb as the primary antibody and
      goat anti-mouse/IgG labeled with colloidal gold as the secondary antibody.
      Electron micrographs of the armyworm midgut tissues showed that the CA-V was
      associated with the midgut epithelia of the insects. These results demonstrated
      the existence of a receptor enacted by CA-V on the midgut cells of the oriental
      armyworm larvae.

PMID- 17002430
TI  - Identification of simple sequence repeat (SSR) markers for acid detergent fiber
      in rice straw by bulked segregant analysis.
AB  - Rice straw is a significant energy source for ruminant animals. The acid
      detergent fiber (ADF) content of rice straw is negatively related to intake
      potential of forages. Therefore, improving the digestibility of rice straw by
      reducing ADF content is a necessary goal in breeding programs. In the present
      study, simple sequence repeat (SSR) markers and the bulked segregant analysis
      (BSA) approach were used to identify molecular markers associated with ADF. A
      total of 121 BC1F1 plants derived from the cross of JX974 (a cultivar with high
      ADF, 36.6%) and Dongxiang wild rice (a wild rice with low ADF, 31.3%), with JX974
      as a recurrent parent, were used to conduct BSA. Phenotypic analysis showed that
      ADF displayed a normal distribution in BC1F1 population, indicating the
      involvement of polygenes. A SSR marker, RM566 on chromosome 9, was identified for
      ADF. A small linkage map consisting of five markers was constructed by adding
      four other markers, and a quantitative trait locus (QTL) controlling ADF was
      mapped at the RM321-RM566 interval, with a distance of 3.9 cM to RM566. This QTL
      explained 12% of the total phenotypic variation of ADF, and its additive effect
      was 3%. This study is the first step to map QTL for ADF, one of the plant cell
      wall components in rice.

PMID- 17002429
TI  - Sequence analysis of a "true" chalcone synthase (chs_H1) oligofamily from hop
      (Humulus lupulus L.) and PAP1 activation of chs_H1 in heterologous systems.
AB  - Screening of a cDNA library of the hop cv. Osvald's 72 and genomic cloning were
      used to isolate members of an oligofamily of chs_H1 genes that codetermine the
      biosynthesis of prenylated chalcones known to be valuable medicinal compounds
      present in hop (Humulus lupulus L.). chs_H1 oligofamily members showed more than
      99% and 98% identity on nucleotide and amino acid levels, respectively, and
      retained all conserved amino acids that form the catalytic center characteristic
      for "true" chalcone synthases. The chs_H1 promoter exhibited low sequence
      variability in addition to conservation of all predicted cis-regulatory elements.
      Possible transactivation of the chs_H1 gene with the transcription factor PAP1
      from Arabidopsis thaliana was assayed using Agrobacterium tumefaciens
      infiltrations of Nicotiana benthamiana and Petunia hybrida plants. Infiltration
      of N. benthamiana leaves with chs_H1 promoter/GUS chimeras led to a 24.8-fold
      increase of the GUS activity when coinfiltrated with the pap1 gene.
      Coinfiltration of the "native" chs_H1 gene with pap1 led to an increased
      accumulation of chs_H1 mRNA as observed by semiquantitative reverse transcription
      polymerase chain reaction. Transgenic lines of P. hybrida expressing the pap1
      gene showed unusual patterns of UV-A-inducible pigmentation and anthocyanin
      accumulation in parenchymatic and medulla cells. Infiltration of transgenic
      leaves of P. hybrida with chs_H1 and pap1 genes arranged as a tandem led to quick
      pigmentation within 12 h after UV-A irradiation. It is indicated that the chs_H1
      promoter contains functional element(s) mediating an efficient response to PAP1
      expression and UV-A irradiation. UV-A also induced chs_H1 mRNA and accumulation
      of flavonol glycosides in hop leaves. It can be expected that the PAP1 factor
      could significantly influence the expression of the chs_H1 oligofamily in
      transgenic hop and modify the hop metabolome.

PMID- 17002431
TI  - Production of Brassica carinata protein hydrolyzates with a high Fischer's ratio
      using immobilized proteases.
AB  - Brassica carinata protein isolates were hydrolyzed using the digestive enzymes
      trypsin, chymotrypsin, and carboxypeptidase A in order to obtain hydrolyzates
      with a high Fischer's ratio. The proteases were immobilized using two glyoxyl
      agarose supports of different porosity, 4 and 10% agarose gels, in order to
      evaluate the effect of substrate diffusion into the support containing the enzyme
      on the hydrolytic process. Reaction time, substrate concentration, and the enzyme
      to substrate ratio were optimized in an attempt to increase the Fischer's ratio
      in the resulting hydrolyzates. Gel filtration chromatography of a hydrolyzate
      with a degree of hydrolysis of 36% yielded a fraction that represented 31% of the
      total hydrolyzed proteins and had a Fischer's ratio of 28.3 with a phenylalanine
      + tyrosine content below 1.5%. This material could be used for preparing special
      diets when there is a need to increase the supply of branched amino acids and/or
      reduce the intake of aromatic amino acids.

PMID- 17002432
TI  - Changes in glucosinolate concentrations, myrosinase activity, and production of
      metabolites of glucosinolates in cabbage (Brassica oleracea Var. capitata) cooked
      for different durations.
AB  - In cabbage, glucosinolates such as sinigrin are hydrolyzed by plant myrosinase to
      allyl isothiocyanate (AITC), allyl cyanide, and, in the presence of an
      epithiospecifier protein, 1-cyano-2,3-epithiopropane (CEP). Isothiocyanates have
      been implicated in the cancer-protective effects of Brassica vegetables. The
      effect of processing on the hydrolysis of glucosinolates was investigated in
      cabbage. Cabbage was steamed or microwaved for six time durations over 7 min.
      Glucosinolate concentrations were slightly reduced after microwave cooking (P <
      0.001) but were not influenced after steaming (P < 0.05). Myrosinase activity was
      effectively lost after 2 min of microwave cooking and after 7 min of steaming.
      Hydrolysis of residual glucosinolates following cooking yielded predominantly CEP
      at short cooking durations and AITC at longer durations until myrosinase activity
      was lost. Lightly cooked cabbage produced the highest yield of AITC on hydrolysis
      in vitro, suggesting that cooking Brassica vegetables for a relatively short
      duration may be desirable from a health perspective.

PMID- 17002433
TI  - Proton transfer reaction-mass spectrometry (PTR-MS) headspace analysis for rapid
      detection of oxidative alteration of olive oil.
AB  - Olive oil has been characterized by rapid proton transfer reaction-mass
      spectrometry (PTR-MS) headspace analysis without any concentration of the
      volatiles or pretreatment of the samples. Comparison of extra virgin and
      defective (rancid) samples, as described by a panel of sensory judges, and the
      monitoring of thermo-oxidation processes are discussed. Multivariate analysis of
      PTR-MS data has been carried out and cross-validated, providing (i) reliable
      classification models for extra virgin oil as opposed to defective oil and (ii)
      calibration models able to predict independently thermo-oxidative degradation and
      the corresponding peroxide value. PTR-MS fragmentation patterns of volatiles
      considered in this study are also reported.

PMID- 17002434
TI  - Changes in volatile and phenolic compounds with malaxation time and temperature
      during virgin olive oil production.
AB  - Virgin olive oils produced at wide ranges of malaxation temperatures (15, 30, 45,
      and 60 degrees C) and times (30, 60, 90, and 120 min) in a complete factorial
      experimental design were discriminated with stepwise linear discriminant analysis
      (SLDA) revealing differences with processing conditions. Virgin olive oils
      produced at 15 and 60 degrees C for 30 min showed the most significant (p < 0.01)
      differences. Discrimination was based upon volatile and phenolic compounds
      detected in olive oils, peroxide value (PV), free fatty acids (FFA), ultraviolet
      (UV) absorbances, and oil yield. There were different discriminating variables
      for processing conditions illustrating the dependence of virgin olive oil quality
      on malaxation time and temperature. Volatile compounds were the dominant
      discriminating variables. Common oxidation indicators of olive oil (PV, K232, and
      K270) were not among the variables that significantly (p < 0.01) changed with
      malaxation time and temperature. Variables that discriminated both malaxation
      time and temperature were hexanal, 3,4-dihydroxyphenyl ethyl alcohol
      decarboxymethyl elenolic acid dialdehyde (3,4-DHPEA-DEDA) and FFA, whereas 1
      penten-3-ol, E-2-hexenal, octane, tyrosol, and vanillic acid significantly (p <
      0.01) changed with temperature only and Z-2-penten-1-ol, (+)-acetoxypinoresinol,
      and oil yield changed with time only. Virgin olive oil quality was significantly
      influenced by malaxation temperature, whereas oil yield discriminated malaxation
      time. This study demonstrates the two modes of hexanal formation: enzymatic and
      nonenzymatic during virgin olive oil extraction.

PMID- 17002435
TI  - Effect of industrial dehydration on the soluble carbohydrates and dietary fiber
      fractions in legumes.
AB  - The effects of soaking, cooking, and industrial dehydration treatments on soluble
      carbohydrates, including raffinose family oligosaccharides (RFOs), and also on
      total dietary fiber (TDF), insoluble dietary fiber (IDF), and soluble (SDF)
      dietary fiber fractions were studied in legumes (lentil and chickpea). Ciceritol
      and stachyose were the main alpha-galactosides for chickpea and lentil,
      respectively. The processing involved a drastic reduction of soluble
      carbohydrates of these legumes, 85% in the case of lentil and 57% in the case of
      chickpea. The processed legume flours presented low residual levels of alpha
      galactosides, which are advisable for people with digestive problems. Processing
      of legumes involved changes in dietary fiber fractions. A general increase of IDF
      (27-36%) due to the increase of glucose and Klason lignin was observed. However,
      a different behavior of SDF was exhibited during thermal dehydration, this
      fraction increasing in the case of chickpea (32%) and decreasing in the case of
      lentil (27%). This is probably caused by the different structures and
      compositions of the cell wall networks of the legumes.

PMID- 17002436
TI  - High molecular weight melanoidins from coffee brew.
AB  - The composition of high molecular weight (HMw) coffee melanoidin populations,
      obtained after ethanol precipitation, was studied. The specific extinction
      coefficient (K(mix)) at 280, 325, 405 nm, sugar composition, phenolic group
      content, nitrogen content, amino acid composition, and non-protein nitrogen (NPN)
      content were investigated. Results show that most HMw coffee melanoidins are
      soluble at high ethanol concentrations. The amino acid composition of the HMw
      fractions was similar, while 17% (w/w) of the nitrogen was NPN, probably
      originating from degraded amino acids/proteins and now part of melanoidins. A
      strong correlation between the melanoidin content, the NPN, and protein content
      was found. It was concluded that proteins are incorporated into the melanoidins
      and that the degree of chemical modification, for example, by phenolic groups,
      determines the solubility of melanoidins in ethanol. Although the existence of
      covalent interaction between melanoidins and polysaccharides were not proven in
      this study, the findings suggest that especially arabinogalactan is likely
      involved in melanoidin formation. Finally, phenolic groups were present in the
      HMw fraction of coffee, and a correlation was found with the melanoidin
      concentration.

PMID- 17002437
TI  - Quantitation of fatty acids, sterols, and tocopherols in turpentine (Pistacia
      terebinthus Chia) growing wild in Turkey.
AB  - The chemical composition (fatty acids, tocopherols, and sterols) of the oil from
      14 samples of turpentine (Pistacia terebinthus L.) fruits is presented in this
      study. The oil content of the samples varied in a relatively small range between
      38.4 g/100 g and 45.1 g/100 g. The dominating fatty acid of the oil is oleic
      acid, which accounted for 43.0 to 51.3% of the total fatty acids. The total
      content of vitamin E active compounds in the oils ranged between 396.8 and 517.7
      mg/kg. The predominant isomers were alpha- and gamma-tocopherol, with approximate
      equal amounts between about 110 and 150 mg/kg. The seed oil of P. terebinthus
      also contained different tocotrienols, with gamma-tocotrienol as the dominate
      compound of this group, which amounted to between 79 and 114 mg/kg. The total
      content of sterols of the oils was determined to be between 1341.3 and 1802.5
      mg/kg, with beta-sitosterol as the predominent sterol that accounted for more
      than 80% of the total amount of sterols. Other sterols in noteworthy amounts were
      campesterol, Delta5-avenasterol, and stigmasterol, which came to about 3-5% of
      the total sterols.

PMID- 17002438
TI  - Characterization of the chemical composition of lotus plumule oil.
AB  - Characterizations of lotus plumule and plumule oil, focusing on approximate
      composition analysis of lotus plumule powder and fatty acid composition, lipid
      classes, triglyceride (TG) profiles, and sterol analysis of the plumule oil, were
      conducted in this work. The results revealed that the lotus plumule constitutes
      7.8% moisture, 4.2% ash, and 12.5% crude oil and 26.3% protein on the dry base.
      Lotus plumule oil is rich in linoleic acid (50.4%) and oleic acid (13.5%), and
      the dominating saturated fatty acids are palmitic acid (18.0%) and behenic acid
      (6.8%). The principal components of TG in lotus plumule oil are LLL (12.80%),
      beta-PLL (11.27%), beta-POL (8.28%), beta-PLO (8.58%), and beta-BeLL (8.32%).
      Lipid class assay of the crude oil gave the saponification value of 153.4 KOH
      mg/g and tocopherol content 390 mg/100 g. A distinct characteristic of lotus
      plumule oil is that its unsaponifiable matter is incredibly high, up to 14-19%,
      which consists mainly of beta-sitosterol (32%), Delta(5)-avenasterol (20%), and
      campesterol (6.3%). The major occurring form of sterols was found to be steryl
      ester. This work might be useful to develop innovative applications of lotus
      plumule oil.

PMID- 17002439
TI  - Effects of different organic farming methods on the concentration of phenolic
      compounds in sea buckthorn leaves.
AB  - The effects of different cultivation methods on the amount of phenolic compounds
      in leaves of 1-year-old seedlings of two Finnish sea buckthorn (Hippophae
      rhamnoides L. ssp. rhamnoides) cultivars 'Terhi' and 'Tytti' were studied in a
      field experiment established at coastal area in Merikarvia, western Finland. The
      cultivation methods included different fertilizers (suitable for organic
      cultivation), mulches (organic and plastic), and land contours (flat vs low hill
      surface). Two experiments were conducted. The first allowed the estimation of the
      effects of cultivar, fertilizer, surface contour, and all their interactions,
      while the other allowed the estimation of the effects of mulches, land contours,
      and their interactions for the cultivar 'Tytti'. Eleven different hydrolyzable
      tannins, pentagalloylglucose, and 14 other phenolic compounds were detected by
      chemical analysis with high-performance liquid chromatography (HPLC). The amount
      of phenolic compounds varied between different land contours and mulches. The
      concentrations of gallic acid, pentagalloylglucose, quercetin-3-rhamnoside,
      monocoumaroyl astragalin A, total hydrolyzable tannins, and condensed tannins
      were significantly higher on the flat surface than on the low hill surface. The
      plastic mulch decreased the concentration of gallic acid, hydrolyzable tannins,
      and condensed tannins compared to the other mulches used. These results suggest
      ways to cultivate sea buckthorn to produce large amounts of valuable chemicals,
      especially tannins in the leaves.

PMID- 17002440
TI  - Understanding the native Californian diet: Identification of condensed and
      hydrolyzable tannins in tanoak acorns (Lithocarpus densiflorus).
AB  - The tanoak (Lithocarpus densiflorus) acorn was a staple food in the Native
      American diet and is still used in traditional dishes. Acorns from the genus
      Quercus have been shown to contain a large range of hydrolyzable tannins.
      However, neither hydrolyzable nor condensed tannins have been characterized in
      tanoak acorns. The aim of this study was to identify the full range of
      hydrolyzable and condensed tannins in extracts of tanoak acorns using liquid
      chromatography/electrospray ionization-mass spectrometry/mass spectrometry.
      Condensed tannins were identified as B type oligomers of (epi)-catechin
      (procyanidins) with a degree of polymerization up to six. Oligomers up to and
      including tetramers were identified by UV spectra and MS detection whereas
      pentamers and hexamers were detected only by MS. The total concentration of
      condensed tannins was 464 mg/100 g acorn pericarp. The concentration of
      propocyanidin monomers, dimers, trimers, and tetramers in acorn pericarp (mg/100
      g acorn pericarp) were 95 +/- 10.9, 148 +/- 35.0, 90 +/- 17.9, and 131 +/- 1.9,
      respectively. No procyanidins were found in the acorn cotyledon tissue. A total
      of 22 hydrolyzable tannins were identified in methanolic extracts of acorn
      cotyledon tissue. Gallic acid derivatives predominated and included galloylated
      esters of glucose, hexahydrodiphenoyl esters of glucose, and methylated gallates.
      Galloylated esters of glucose were present as isomers of galloyl glucose,
      digalloyl glucose, and trigalloyl glucose. Mass spectral fragmentation patterns
      indicate the presence of one gallic acid-galloyl glucose isomer and two gallic
      acid-digalloyl-glucose isomers. No isomers of tetragalloyl glucose and
      pentagalloyl glucose were identified. Ellagic acid and ellagic acid pentoside
      were also identified.

PMID- 17002441
TI  - Metabolite profiling of grape: Flavonols and anthocyanins.
AB  - Flavonols are products of the flavonoid biosynthetic pathway, which also give
      rise to anthocyanins and condensed tannins in grapes. We investigated their
      presence in the berry skins of 91 grape varieties (Vitis vinifera L.), in order
      to produce a classification based on the flavonol profile. The presence of
      laricitrin 3-O-galactoside and syringetin 3-O-galactoside in red grapes is
      reported here for the first time. In red grapes, the main flavonol was quercetin
      (mean = 43.99%), followed by myricetin (36.81%), kaempferol (6.43%), laricitrin
      (5.65%), isorhamnetin (3.89%), and syringetin (3.22%). In white grapes, the main
      flavonol was quercetin (mean = 81.35%), followed by kaempferol (16.91%) and
      isorhamnetin (1.74%). The delphinidin-like flavonols myricetin, laricitrin, and
      syringetin were missing in all white varieties, indicating that the enzyme
      flavonoid 3',5'-hydroxylase is not expressed in white grape varieties. The
      pattern of expression of flavonols and anthocyanins in red grapes was compared,
      in order to gain information on the substrate specificity of enzymes involved in
      flavonoid biosynthesis.

PMID- 17002442
TI  - Near-infrared reflectance spectroscopy for predicting amino acids content in
      intact processed animal proteins.
AB  - Near-infrared calibrations were developed for the instantaneous prediction of
      amino acids composition of processed animal proteins (PAPs). Two sample
      presentation modes were compared (ground vs intact) for demonstrating the
      viability of the analysis in the intact form, avoiding the need for milling.
      Modified partial least-squares (MPLS) equations for the prediction of amino acids
      in PAPs were developed using the same set of samples (N = 92 PAPs) analyzed in
      ground and intact form and in three cups differing in the optical window size.
      The standard error for cross validation (SECV) and the coefficient of
      determination (1-VR) values yielded with the calibrations developed using the
      samples analyzed in the intact form showed similar or even better accuracy than
      those obtained with finely ground samples. The excellent predictive ability (1-VR
      > 0.90; CV < 3.0%) obtained for the prediction of amino acids in intact processed
      animal proteins opens an enormous expectative for the on-line implementation of
      NIRS technology in the processing and marketing of these important protein feed
      ingredients, alleviating the costs and time associated with the routine quality
      controls.

PMID- 17002443
TI  - Chemical composition of clarified bayberry (Myrica rubra Sieb. et Zucc.) juice
      sediment.
AB  - Clarified bayberry juice turned hazy upon storage at 25 degrees C for 6 months,
      and the chemical composition of centrifugally separated sediment was analyzed.
      Bayberry juice haze was mainly protein-tannin haze. The lyophilized sediment
      contained 20.4 +/- 4.3% of protein, 70.2 +/- 2.6% of total polyphenols, 7.2% of
      monosaccharides, and 6.7 +/- 0.6% of ash. Amino acid analyses and molecular
      weight distribution estimation indicated that bayberry proteins were haze-active
      proteins with a molecular weight less than 8 kDa. Gallic acid, quercetin
      hexoside, quercetin deoxyhexoside, and quercetin were found in the methanol
      dissolved sample, while gallic acid, protocatechuic acid, cyanidin, ellagic acid,
      and quercetin were detected in the acid-hydrolyzed sample. Ellagic acid was the
      dominant individual phenolic (9.9 +/- 0.19 g/100 g dry weight, 55.3% of the total
      amount) in the sediment. Monosaccharides of rhamnose, arabinose, mannose,
      glucose, and galactose in the sediment were most probably the glycoside moieties
      of the anthocyanins, flavonols, and elllagitannins. Metal ions of calcium,
      magnesium, potassium, iron, and copper also indicated the heterogeneous
      characteristics of the sediment.

PMID- 17002444
TI  - Antioxidant activities and anthocyanin content of fresh fruits of common fig
      (Ficus carica L.).
AB  - Fig fruit has been a typical component in the health-promoting Mediterranean diet
      for millennia. To study the potential health-promoting constituents of fig
      fruits, six commercial fig varieties differing in color (black, red, yellow, and
      green) were analyzed for total polyphenols, total flavonoids, antioxidant
      capacity, and amount and profile of anthocyanins. Using reversed-phase liquid
      chromatography (RP-LC), various concentrations of anthocyanins but a similar
      profile was found in all varieties studied. Hydrolysis revealed cyanidin as the
      major aglycon. Proton and carbon NMR confirmed cyanidin-3-O-rhamnoglucoside
      (cyanidin-3-O-rutinoside; C3R) as the main anthocyanin in all fruits. Color
      appearance of fig extract correlated well with total polyphenols, flavonoids,
      anthocyanins, and antioxidant capacity. Extracts of darker varieties showed
      higher contents of phytochemicals compared to lighter colored varieties. Fruit
      skins contributed most of the above phytochemicals and antioxidant activity
      compared to the fruit pulp. Antioxidant capacity correlated well with the amounts
      of polyphenols and anthocyanins (R2 = 0.985 and 0.992, respectively). In the dark
      colored Mission and the red Brown-Turkey varieties, the anthocyanin fraction
      contributed 36 and 28% of the total antioxidant capacity, respectively. C3R
      contributed 92% of the total antioxidant capacity of the anthocyanin fraction.
      Fruits of the Mission variety contained the highest levels of polyphenols,
      flavonoids, and anthocyanins and exhibited the highest antioxidant capacity.

PMID- 17002445
TI  - Synthesis and herbicidal activity of N,N-diethyl-3-(arylselenonyl)-1H-1,2,4
      triazole-1-carboxamide.
AB  - Based on the carbamoyl triazole herbicide Cafenstrole, 12 novel selenium
      containing compounds were designed and synthesized. All of the compounds were
      characterized and confirmed by IR, 1H NMR, and high-resolution mass spectroscopy.
      The bioassay tests showed that some of the compounds (C2, C4, C(7-8), and C12)
      exhibited good inhibitory activity against cucumber (Cucumis sativus L.) and
      semen euphorbiae (Leptochloa chinensis N.). Especially, compound C6 inhibited the
      growth of cucumber and semen euphorbiae by >90% at a concentration of 1.875
      microg/mL, and the inhibition of the compound on the rice (Oryza sativa L.) was
      only 8.3% at a concentration of 7.5 microg/mL, which indicated a higher
      selectivity between weed and rice than that shown by Cafenstrole.

PMID- 17002446
TI  - Leaf surface sesquiterpene alcohols of the potato (Solanum tuberosum) and their
      influence on colorado beetle (Leptinotarsa decemlineata Say) feeding.
AB  - The structures of two previously unknown sesquiterpene alcohols of the potato
      (Solanum tuberosum) were assigned. The potato alcohols were obtained by steam
      distillation, preparative column chromatography, and separation into fractions by
      HPLC on a silica gel column. The fractions were studied by GC-FID, GC-MS, and NMR
      spectroscopy. The potato sesquiterpene alcohols were identified as kunzeaol (6
      alpha-hydroxygermacra-1(10),4-diene) and ledol. These two compounds were used in
      feeding tests with larvae and beetles of the Colorado potato beetle (Leptinotarsa
      decemlineata Say). In a bioassay, kunzeaol was found to act as a feeding
      attractant for the beetles.

PMID- 17002447
TI  - Antioxidative effect of quercetin and its equimolar mixtures with phenyltin
      compounds on liposome membranes.
AB  - Our earlier studies have shown that the compounds diphenyltin dichloride (DPhT)
      and triphenyltin chloride (TPhT) in the presence of UVC radiation enhanced the
      degree of phosphatidylcholine liposome membrane oxidation (J. Agric. Food Chem.
      2005, 53, 76-83). The prooxidative behavior of the compounds has now been
      confirmed with the electron paramagnetic resonance method, which proved the
      possibility that the studied compounds can exist in free radical forms. The
      present work investigates the possibility of the protective action of quercetin
      on phosphatidylcholine liposome membranes exposed to the prooxidative action of
      DPhT and TPhT induced by UV radiation (lambda = 253.7 nm). The concentrations of
      quercetin and its equimolar mixtures with DPhT and TPhT were determined (and
      compared with well-known antioxidants as standards-trolox and butylated
      hydroxytoluene, also in the presence of phenyltins) as those that induce 50%
      inhibition in oxidation of liposomes radiated with UV. They are 5.1 +/- 0.10, 2.9
      +/- 0.12, and 1.9 +/- 0.08 microM (differences between the values are
      statistically significant), constituting the following sequence of antioxidative
      activity: quercetin:TPhT > quercetin:DPhT > quercetin. This relation is confirmed
      by the results on the antiradical ability of quercetin and its mixtures with DPhT
      and TPhT toward the free radical 1,1-diphenyl-2-pricrylhydrazil. Similar
      sequences obtained in both studies suggest a possible mechanism of the
      antiradical action of the mixtures as free radical scavengers. We suggested that
      (i) quercetin's ability, documented by spectrophotometric, infrared attenuated
      total reflectance spectroscopy, (1)H NMR, and molecular modeling methods, to form
      complexes with phenyltins indicates a possible way of protection against the
      peroxidation caused by the free radical forms of phenyltins and (ii) the
      differentiation in the action of the quercetin/TPhT and quercetin/DPhT associates
      (statisticaly significant) may result from a different localization in the
      liposome membrane, which is indicated by the results of the fluorimetric studies.

PMID- 17002448
TI  - Sample extraction method combining micellar extraction-SPME and HPLC for the
      determination of organochlorine pesticides in agricultural soils.
AB  - A method for the determination of organochlorine pesticides in soil samples
      combining microwave assisted micellar extraction (MAME) with solid-phase
      microextraction (SPME) and high-performance liquid chromatography-UV has been
      developed. A mixture of two nonionic surfactants (polyoxyethylene 10 lauryl ether
      and polyoxyethylene 10 stearyl ether) was used for the extraction of pesticides
      from agricultural soils, and different types of SPME fibers were compared. The
      different parameters which affect extraction efficiency in the SPME procedure
      were optimized such as extraction time and temperature. The method developed
      involves extraction and preconcentration for the target analytes in soil samples.
      The analytical parameters were also studied and good recoveries obtained, RSD
      being lower than 10% and detection limits ranging between 36 and 164 ng g(-1) for
      the pesticides studied. The proposed method was successfully applied to the
      determination of some organochlorine pesticides in several kinds of agricultural
      soil samples with different characteristics.

PMID- 17002449
TI  - Reaction of thiometon and disulfoton with reduced sulfur species in simulated
      natural environment.
AB  - The reactions of thiometon and its ethyl analogue, disulfoton, with reduced
      sulfur species [e.g., bisulfide (HS-), polysulfide (S(n)2-), thiophenolate (PhS
      ), and thiosulfate (S2O3(2-))] were examined in well-defined aqueous solutions
      under anoxic conditions. The role of reduced sulfur species was investigated in
      the abiotic degradation of thiometon and disulfoton. Experiments at 25 degrees C
      demonstrated that HS-, S(n)2-, PhS-, and S2O3(2-) promoted the degradation of
      thiometon to a great extent while only S(n)2- and PhS- showed a small
      accelerating effect in the degradation of disulfoton. Reactions were monitored at
      varying concentrations of reduced sulfur species to obtain the second-order rate
      constants. The reactivity of the reduced sulfur species decreased in the
      following order: S(n)2- > PhS- > HS- approximately S2O3(2-). Transformation
      products were confirmed by standards or characterized by gas chromatography mass
      spectrometry. The results illustrate that multiple pathways occur in the
      reactions with reduced sulfur species, among which the nucleophilic attack at the
      alpha-carbon of the alkoxy group was the predominant pathway. Activation
      parameters of the reaction of thiometon and disulfoton with HS- were also
      determined from the measured second-order rate constants over a temperature
      range. DeltaH( not equal) values indicated that the reactivity of thiometon
      toward HS- was much greater than for disulfoton. Nucleophilic attack at the
      alkoxy group was more important for thiometon than disulfoton. When the measured
      second-order rate constants at 25 degrees C are multiplied by [HS-] and
      Sigma[S(n)2-] reported in saltmarsh porewaters, predicted half-lives show that
      reduced sulfur species present at environmentally relevant concentrations may
      present an important sink for thiometon in coastal marine environments.

PMID- 17002450
TI  - Competitive sorption-desorption behavior of triazine herbicides with plant
      cuticular fractions.
AB  - Sorption interactions of plant cuticular matter with organic compounds are not
      yet fully understood. The objective of this study was to examine the competitive
      sorption-desorption interactions of the triazine herbicides (atrazine and
      ametryn) with cuticular fractions isolated from tomato fruits and leaves of Agave
      americana. The 13C NMR data suggest a rubber-like nature for the cutin. This
      biopolymer exhibited reversible and noncompetitive sorption. Enhanced desorption
      of atrazine was recorded in the bi-solute system with bulk and dewaxed A.
      americana cuticles. 13C NMR analyses of these samples suggested that the sorbed
      competitor ametryn facilitated a physical phase transition of rigid paraffinic
      sorption domain to mobile and flexible domain during sorption process. We suggest
      that the different sorption-desorption behavior obtained for the two cuticles is
      related to the higher content of waxes (14% vs 2.6%) and lower content of cutin
      (46% vs 75%) in the A. americana versus tomato fruit cuticle.

PMID- 17002451
TI  - Development of inosine monophosphate and its degradation products during aging of
      pork of different qualities in relation to basic taste and retronasal flavor
      perception of the meat.
AB  - Inosine monophosphate (IMP) and its degradation products, ribose and
      hypoxanthine, are all considered to be important constituents in meat flavor
      formation and development. The present study explored the fate of IMP during the
      aging of two qualities of pork (pH >5.7 and 5.5 < pH < 5.6) and the potential
      relationship between IMP, hypoxanthine, and sensory attributes of pork registered
      both as retronasal and basic taste responses in whole meat, meat juice, and the
      remaining meat residue. During aging the concentration of IMP decreased with a
      simultaneous increase in the concentrations of inosine, hypoxanthine, and ribose.
      The rates at which IMP was degraded to inosine and inosine to hypoxanthine during
      aging were found to be in agreement with the known rate constants of the
      dephosphorylation of IMP and the hydrolysis of inosine, respectively. Moreover,
      high-pH pork resulted in a significantly higher concentration of hypoxanthine
      throughout storage compared with low-pH pork due to an initially higher
      concentration of IMP in high-pH meat. The sensory analysis showed increasing
      intensity in bitterness and saltiness of pork as a function of aging, with the
      intensity being most pronounced in the meat juice. The increasing bitterness of
      the pork as a function of aging coincided with the higher content of hypoxanthine
      in these samples, thereby suggesting that degradation of IMP to hypoxanthine
      might influence pork flavor. In contrast, IMP was associated with nonaged meat
      and the sensory attributes meaty and brothy.

PMID- 17002452
TI  - Composition of the volatile fraction of Ocotea bofo Kunth (Lauraceae) calyces by
      GC-MS and NMR fingerprinting and its antimicrobial and antioxidant activity.
AB  - The chemical composition of the essential oil obtained by steam distillation of
      the floral calyces of Ocotea bofo Kunth (Lauraceae) was studied by means of GC,
      GC-MS, and 1H, 13C, and bidimensional NMR (COSY, HSQC, HMBC). Twenty-five
      constituents were identified, and estragole (48.7%), alpha-phellandrene (19.6%)
      and sabinene (10.4%) were found to be the major components. Antimicrobial
      activity against six aerobic bacteria and five yeasts and antioxidant activity
      performed by photochemiluminescence (PCL), 1,1-diphenyl-2-picrylhydrazyl (DPPH),
      and beta-carotene bleaching assays are reported. The oil showed fair inhibiting
      properties against bacteria and a good inhibition against most yeasts. Its
      radical scavenging and chain-breaking antioxidant properties were comparable to
      or better than those provided by synthetic controls. Particular emphasis has been
      given to the use of NMR as a fast and reliable tool to discriminate O. bofo
      essential oil from other commercial anethole- and estragole-rich oils, namely,
      Illicium verum, Foeniculum vulgare, and Artemisia dracunculus.

PMID- 17002453
TI  - Characterization and semiquantitative analysis of volatiles in seedless
      watermelon varieties using solid-phase microextraction.
AB  - Seedless triploid watermelons have increased in popularity since the early 1990s,
      and the demand for seedless fruit is on the rise. Sweetness and sugars are
      crucial breeding focuses for fruit quality. Volatiles also play an important
      role; yet, we found no literature for seedless varieties and no reports using
      solid-phase microextraction (SPME) in watermelon. The objective of this
      experiment was to identify volatile and semivolatile compounds in five seedless
      watermelon varieties using carboxen divinylbenzene polydimethylsiloxane solid
      phase microextraction (SPME) with gas chromatography-mass spectrometry (GC-MS).
      Fully ripe watermelon was squeezed through miracloth to produce rapid juice
      extracts for immediate headspace SPME GC-MS. Aldehydes, alcohols, ketones, and
      one furan (2-pentyl furan, a lipid oxidation product) were recovered. On the
      basis of total ion count peak area, the most abundant compounds in five varieties
      were 3-nonen-1-ol/(E,Z)-2,6-nonadienal (16.5-28.2%), (E)-2-nonenal (10.6-22.5%),
      and (Z)-6-nonenal (2.0-11.3%). Hexanal was most abundant (37.7%) in one variety
      (Petite Perfection) [corrected] The most abundant ketone was 6-methyl-5-hepten-2
      one (2.7-7.7%). Some sensory attributes reported for these compounds are melon,
      citrus, cucumber, orange, rose, floral, guava, violet, vegetable, green, grassy,
      herbaceous, pungent, fatty, sweet, and waxy. Identifying and relating these
      compounds to sensory attributes will allow for future monitoring of the critical
      flavor compounds in seedless watermelon after processing and throughout fresh-cut
      storage.

PMID- 17002454
TI  - Flavored yogurt complex viscosity influences real-time aroma release in the mouth
      and sensory properties.
AB  - The influence of flavored yogurt texture on aroma perception and in-nose aroma
      release measured by atmospheric pressure chemical ionization mass spectrometry
      analysis was investigated. The study was carried out on six yogurts varied by
      protein composition and mechanical treatment. For the same matrix composition,
      the complex viscosity of yogurts influenced in-nose release and perception. After
      swallowing, aroma release and intensity of olfactory perception were stronger in
      low-viscosity yogurts than in high-viscosity yogurts. Moreover, the protein
      composition influenced aroma release only when yogurts exhibited wide variations
      of complex viscosity and consequently texture. In mouth, aroma release and
      perception were influenced more by yogurt mechanical treatment than by protein
      composition. On the basis of mass transfer analysis, the main physical mechanism
      which could explain the difference in aroma release would be the surface exchange
      area developed in the mouth and in the throat.

PMID- 17002455
TI  - Effect of the pH of heating on the qualitative and quantitative compositions of
      the sera of reconstituted skim milks and on the mechanisms of formation of
      soluble aggregates.
AB  - The effect of the pH of heating (6.3-7.3) on the composition of sera in
      reconstituted skimmed milks was investigated. A combination of SDS-PAGE analysis
      and size exclusion chromatography (SEC) combined with an original approach to the
      analysis of the SEC profiles was performed. The composition of the sera varied
      greatly when the pH of heating was adjusted below and above the natural pH of
      milk. The formation, composition, and concentration of heat-induced soluble
      complexes depended on the combination of the effect of adjusting the pH of the
      milk and the heat treatment. Two types of mechanism for the formation of soluble
      aggregates appeared to exist, depending on the pH of the milk. The first type
      results from the formation of WP/kappa-casein aggregates at the surface of the
      micelle, and these were detached partially into the serum in larger amount as the
      pH increased up to 6.7, where it reaches a maximum. The second type of complexes,
      whose amount increased as the pH of heating increased from 6.7 to 7.3, may be
      formed between caseins (kappa- but also perhaps some alpha(s)-casein) and
      aggregated WP resulting in complexes that are smaller in size and with a higher
      kappa-casein/whey protein ratio than the first type.

PMID- 17002456
TI  - Effect of seed development stage on sphingolipid and phospholipid contents in
      soybean seeds.
AB  - Glucosylceramide (GlcCer) and ceramide (Cer) are the predominant sphingolipids
      (SL) in soybeans. They have been recognized as functional components in plants
      and may have health benefits for humans. The objective of this study was to
      evaluate the changes in SL and phospholipid (PL) contents that occurred during
      seed development. Soybean seeds of three cultivars (IA1008, IA1010, and IA1014)
      were harvested at 5-day intervals from 28 days after flowering (DAF) to 68 DAF
      (mature seed). SL and PL contents of seeds were quantified using high-performance
      liquid chromatography (HPLC) with an evaporative light scattering detector
      (ELSD). SL and PL contents decreased significantly during seed development.
      Averaged across cultivars, Cer content on a dry weight basis decreased from 51.4
      nmol/g at 28 DAF to 22.2 nmol/g at 68 DAF, whereas GlcCer content decreased from
      522.8 nmol/g at 28 DAF to 135.8 nmol/g at 68 DAF. PL percentage of the total
      lipid decreased from 9.1% at 28 DAF to 3.5% at 68 DAF.

PMID- 17002457
TI  - Phospholipid-based microemulsions suitable for use in foods.
AB  - The preparation of nonaqueous microemulsions using food-acceptable components is
      reported. The effect of oil on the formation of microemulsions stabilized by
      lecithin (Epikuron 200) and containing propylene glycol as immiscible solvent was
      investigated. When the triglycerides were used as oil, three types of phase
      behavior were noted, namely, a two-phase cloudy region (occurring at low lecithin
      concentrations), a liquid crystalline (LC) phase (occurring at high surfactant
      and low oil concentrations), and a clear monophasic microemulsion region. The
      extent of this clear one-phase region was found to be dependent upon the
      molecular volume of the oil being solubilized. Large molecular volume oils, such
      as soybean and sunflower oils, produced a small microemulsion region, whereas the
      smallest molecular volume triglyceride, tributyrin, produced a large, clear
      monophasic region. Use of the ethyl ester, ethyl oleate, as oil produced a clear,
      monophasic region of a size comparable to that seen with tributyrin. Substitution
      of some of the propylene glycol with water greatly reduced the extent of the
      clear one-phase region and increased the extent of the liquid crystalline region.
      In contrast, ethanol enhanced the clear, monophasic region by decreasing the LC
      phase. Replacement of some of the lecithin with the micelle-forming nonionic
      surfactant Tween 80 to produce mixed lecithin/Tween 80 mixtures of weight ratios
      (Km) 1:2 and 1:3 did not significantly alter the phase behavior, although there
      was a marginal increase in the area of the two-phase, cloudy region of the phase
      diagram. The use of the lower phosphatidylcholine content lecithin, Epikuron 170,
      in place of Epikuron 200 resulted in a reduction in the LC region for all of the
      systems investigated. In conclusion, these studies show that it is possible to
      prepare one-phase, clear lecithin-based microemulsions over a wide range of
      compositions using components that are food-acceptable.

PMID- 17002458
TI  - Mode of de-esterification of alkaline and acidic pectin methyl esterases at
      different pH conditions.
AB  - Highly esterified citrus pectin was de-esterified at pH 4.5 and 8.0 by a fungal
      pectin methyl esterase (PME) that was shown to have an acidic isoelectric pH (pI)
      and an acidic pH optimum and by a plant PME that was characterized by an alkaline
      pI and an alkaline pH optimum. Interchain and intrachain de-esterification
      patterns were studied by digestion of the pectin products with endo
      polygalacturonase and subsequent analysis using size exclusion and anion-exchange
      chromatography. No effect of pH was observed on the de-esterification mode of
      either of the two enzymes. Acidic, fungal PME converted pectin according to a
      multiple-chain mechanism, with a limited degree of multiple attack at the
      intrachain level, both at pH 4.5 and at pH 8.0. A multiple-attack mechanism, with
      a high degree of multiple attack, was more appropriate to describe the action
      mode of alkaline, plant PME, both at pH 4.5 and at pH 8.0.

PMID- 17002459
TI  - Water-soluble carbohydrates and fructan structure patterns from Agave and
      Dasylirion species.
AB  - Fructans, storage carbohydrates with beta-fructofuranosyl linkages, are found in
      approximately 15% of higher plants. The metabolic flexibility of those molecules
      allows them easily to polymerize and depolymerize to soluble carbohydrates
      according to plant development stage and environmental conditions. In this work,
      water-soluble carbohydrates, including fructan structure patterns, were compared
      among Agave and Dasylirion species grown in different environmental regions in
      Mexico. Fructans were the main storage carbohydrate present in Agave stems, in
      addition to other carbohydrates related to its metabolism, whereas Dasylirion
      spp. presented a different carbohydrate distribution. A good correlation of water
      soluble carbohydrate content with climatic conditions was observed. Fructans in
      Agave and Dasylirion genera were found in the form of polydisperse molecules,
      where structural heterogeneity in the same plant was evidenced by methylation
      linkage analysis and chromatographic methods. Fructans from the studied species
      were classified into three groups depending on DP and linkage-type abundance.
      These storage carbohydrates share structural characteristics with fructans in
      plants that belong to the Asparagales members. Agave and Dasylirion fructans can
      be categorized as graminans and branched neo-fructans, which we have termed
      agavins.

PMID- 17002460
TI  - Stabilization of beef meat by a new active packaging containing natural
      antioxidants.
AB  - A new antioxidant active packaging material for food has been designed and
      developed, consisting of a polypropylene film in which some natural antioxidants
      have been immobilized. The antioxidant properties of the new material have been
      tested by using both pure myoglobin and fresh beef steaks. Two different cell
      configurations (glass vial and Petri dish) and four different myoglobin
      concentrations-according to the common content of this compound in fresh meat and
      meat derivatives (1080, 1995, 3332, and 4414 microg g(-1), respectively)-have
      been evaluated in oxidation studies. Furthermore, three different concentrations
      of natural antioxidants in the film (designated as PR1, PR2, and PR3) were
      evaluated. Once myoglobin samples and the active films were introduced in the
      cell, they were exposed to cool white fluorescent light to accelerate oxidation
      for a period of time ranging from 5 to 30 days. Remaining myoglobin concentration
      was measured by molecular absorption UV-vis spectrophotometry at 409 nm.
      Organoleptic properties and color, texture, and physical characteristics of fresh
      meat packaged with the new active film have also been measured to evaluate the
      shelf life of the packaged meat. Results showed that, compared to normal
      polypropylene, the active film containing natural antioxidants efficiently
      enhanced the stability of both myoglobin and fresh meat against oxidation
      processes, thus being a promising way to extend the shelf life of fresh meat.

PMID- 17002461
TI  - Impact of pH on the kinetics of acrylamide formation/elimination reactions in
      model systems.
AB  - The effect of pH on acrylamide formation and elimination kinetics was studied in
      an equimolar (0.1 M) asparagine-glucose model system in phosphate or citrate
      buffer, heated at temperatures between 120 and 200 degrees C. To describe the
      experimental data, a simplified kinetic model was proposed and kinetic parameters
      were estimated by combined nonlinear regression and numerical integration on the
      data obtained under nonisothermal conditions. The model was subsequently
      validated in a more realistic potato-based matrix with varying pH. By increasing
      acidity, the reaction rate constants at T(ref) (160 degrees C) for both
      acrylamide formation and elimination can significantly be reduced, whereas the
      temperature dependence of both reaction rate constants increases. The
      introduction of a lyophilized potato matrix (20%) did not affect the acrylamide
      formation reaction rate constant at reference temperature (160 degrees C) as
      compared to the asparagine-glucose model system; the elimination rate constant at
      T(ref), on the contrary, was almost doubled.

PMID- 17002462
TI  - Mechanism for lactate-color stabilization in injection-enhanced beef.
AB  - In two experiments, the relationship between metmyoglobin (MMb) reduction and
      lactate to pyruvate conversion with concomitant production of reduced
      nicotinamide adenine dinucleotide (NADH) via lactic dehydrogenase (LDH) was
      investigated. In experiment 1, nonenzymatic reduction of horse MMb occurred in a
      lactate-LDH-NAD system. Exclusion of NAD+, L-lactic acid, or LDH resulted in
      minimal MMb reduction. Increasing NAD+ and L-lactic acid concentrations increased
      reduction. In experiment 2, beef strip loins (longissimus lumborum muscle) were
      injected with combinations of potassium lactate, sodium tripolyphosphate, sodium
      chloride, and/or sodium acetate. Steaks were packaged in high-oxygen (80%
      oxygen/20% carbon dioxide) modified-atmosphere packaging and stored for 2-9 days
      and then placed in a fluorescent-lighted, open-top display case for 5 days at 1
      degrees C. Enhancing loins with 2.5% potassium lactate significantly increased
      LDH activity, NADH concentration, MMb-reducing activity, and subsequent color
      stability during display. These research results support the hypothesis that
      enhancing beef with lactate replenishes NADH via increased LDH activity,
      ultimately resulting in greater meat color stability.

PMID- 17002463
TI  - Treatment of cereal products with a tailored preparation of trichoderma enzymes
      increases the amount of soluble dietary fiber.
AB  - Nutritionists recommend increasing the intake of soluble dietary fiber (SDF),
      which is very low in most cereal-based products. Conversion of insoluble DF (IDF)
      into SDF can be achieved by chemical treatments, but this affects the sensorial
      properties of the products. In this study, the possibility of getting a
      substantial increase of SDF from cereal products using a tailored preparation of
      Trichoderma enzymes is reported. Enzymes were produced cultivating Trichoderma
      using durum wheat fiber (DWF) and barley spent grain (BSG) as unique carbon
      sources. Many Trichoderma strains were screened, and the hydrolysis conditions
      able to increase by enzymatic treatment the amount of SDF in DWF and BSG were
      determined. Results demonstrate in both products that it is possible to triple
      the amount of SDF without a marked decrease of total DF. The enzymatic treatment
      also causes the release of hydroxycinnamic acids, mainly ferulic acid, that are
      linked to the polysaccharides chains. This increases the free phenolic
      concentration, the water-soluble antioxidant activity, and, in turn, the phenol
      compounds bioavailability.

PMID- 17002464
TI  - Thermal and viscoelastic properties of kappa/iota-hybrid carrageenan gels
      obtained from the Portuguese seaweed Mastocarpus stellatus.
AB  - The potential use of the underexploited Portuguese seaweed Mastocarpus stellatus
      as a source of natural thickening and gelling agents for food applications has
      been investigated. The alkaline pretreatment duration and extraction parameters
      (pH, temperature, and extraction duration) of seaweeds have been systematically
      varied in order to produce kappa/iota-hybrid carrageenans exhibiting a wide range
      of chemical properties. The mechanical spectra and the setting and melting
      temperatures of gels obtained by cooling 1.5 wt % extracted biopolymers solutions
      in 0.05 mol/dm3 KCl were measured by means of small amplitude oscillatory shear
      experiments. Gels showing elastic storage moduli ranging from 250 to 2750 Pa with
      no water syneresis could be obtained, and the relationships between the thermal
      properties and elasticity of the gels were evidenced. Gels mechanical properties
      are shown to correlate well with polysaccharides chemical parameters such as the
      degree of sulfate groups, the molecular weight distribution, and the relative
      content in iota-carrageenan monomers as determined by FTIR spectroscopy.

PMID- 17002465
TI  - Role of proteins in oil-in-water emulsions on the stability of lipid
      hydroperoxides.
AB  - The purpose of this research was to better understand the mechanisms by which
      proteins affect the rates of lipid oxidation in order to develop protein
      stabilized emulsion delivery systems with maximal oxidative stability. This study
      evaluated the affect of pH and emulsifier concentration on the stability of
      cumene hydroperoxide in hexadecane-in-water emulsions stabilized by beta
      lactoglobulin (beta-Lg). Emulsions prepared with 0.2 wt % beta-Lg (at pH 7.0)
      showed a 26.9% decrease in hydroperoxide concentrations 5 min after 0.25 mM
      ferrous ion was added to the emulsion. EDTA, but not continuous phase beta-Lg,
      could inhibit iron-promoted lipid hydroperoxide decomposition. Lipid
      hydroperoxides were more stable to iron-promoted degradation at pH values below
      the pI of beta-Lg, where the emulsion droplet would be cationic and thus able to
      repel iron away from the lipid hydroperoxides. Heating the beta-Lg-stabilized
      emulsions to produce a cohesive protein layer on the emulsion droplet surface did
      not alter the ability of iron to decompose lipid hydroperoxides. These results
      suggest that proteins at the interface of emulsion droplets primarily stabilize
      lipid hydroperoxides by electrostatically inhibiting iron-hydroperoxide
      interactions.

PMID- 17002466
TI  - Production of galacto-manno-oligosaccharides from guar gum by beta-mannanase from
      Penicillium oxalicum SO.
AB  - Beta-mannanase from Penicillium oxalicum SO efficiently hydrolyzed guar
      galactomannan to galacto-manno-oligosaccharides. Gel filtration estimated the
      molecular weight of the beta-mannanase as 35 000 and SDS-PAGE as 29 000. The
      optimum pH was around 5 while a stable pH was reached in the range of 3-6.
      Optimum temperature was around 60 degrees C at pH 5, while under 60 degrees C
      activity was stable. HPLC analysis detected oligosaccharides with degrees of
      polymerization (DP) of 2 to 7 and 2 to 6 released on hydrolysis of guar and
      locust bean gums, respectively; about 92% of the released sugars were
      oligosaccharides. In analysis of the sugar distribution on MALDI-TOF-MS, major
      products of DP 6 and 7 and DP 5 and 6 were confirmed in hydrolysates of guar gum
      and locust bean gum, respectively. One of the main oligosaccharides released from
      guar gum, with DP 7, had a high galactose content (Gal/Man = 0.76) and
      corresponded to a blockwise galactose-substituted mannan type in galactomannan.

PMID- 17002467
TI  - Fourier transform raman spectroscopy study of heat-induced gelation of plasma
      proteins as influenced by pH.
AB  - Fourier transform (FT) Raman spectroscopy was used to elucidate heat-induced
      structural changes of albumin, globulins, serum, and plasma protein solutions
      (15% w/w) as affected by pH (4.5, 6.0, and 7.5). Reduction of alpha-helix and
      formation of beta-sheet, disulfide bond reactions, and exposure and buriedness of
      hydrophobic groups and amino acid residues were observed. All of these features
      contributed to the formation of strong, irreversible heat-induced gels. The
      application of a dimensionality reducing technique such as principal component
      analysis proved to be useful to determine the most influential qualities of
      protein samples, as well as the pH-dependent behavior of some of the attributes
      of both unheated and heated solutions. Analysis of Raman spectra in terms of
      differences demonstrated the interactions of albumin and globulins in co
      occurrence and the significant role of fibrinogen on the gel's attributes.

PMID- 17002468
TI  - Isolation and characterization of a thermally extracted yeast cell wall fraction
      potentially useful for improving the foaming properties of sparkling wines.
AB  - Two different yeast cell wall extracts were obtained using enzymatic digestion
      and thermal treatment. The effects of the extracts obtained on the foaming
      properties of a model wine and two sparkling wines were studied. The model wine
      and sparkling wines, supplemented with the thermal extract, presented better
      foaming properties than did the samples supplemented with the enzymatic extract.
      The fractioning (Con A chromatography) and characterization (SDS-PAGE, SEC, GC,
      and RP-HPLC) of both extracts showed that the fraction responsible for the
      foaming properties is constituted by mannoproteins with a relative molecular
      weight between 10 and 30 kDa, presenting an equilibrated composition of the
      hydrophobic and hydrophilic protein domains. This thermal extract did not modify
      the protein stability in both the model wine and the sparkling wines. These
      results demonstrate that the enrichment of a sparkling wine with mannoproteins
      extracted by mild heat procedures will contribute to improving its foaming
      properties.

PMID- 17002469
TI  - Tartaric acid recovery from distilled lees and use of the residual solid as an
      economic nutrient for lactobacillus.
AB  - The recovery of tartaric acid (TA) from distilled vinification lees coming from
      the white and red winemaking technology was optimized using response surface
      methodology and Statistica 5.0 software. The sequential treatment of dissolving
      TA and further calcium tartrate (CaT) precipitation could be used to recover up
      to 92.4% of the initial TA when distilled white lees were used. The residual lees
      were employed as economic nutrients for lactic acid production by Lactobacillus
      pentosus CECT-4023 using hemicellulosic vine shoot hydrolysates as carbon source.
      Distilled lees after TA extraction used as nutrients provided values of lactic
      acid (18.4-18.9 g/L), global volumetric productivities (0.82-0.84 g/L.h), and
      product yields (0.69-0.70 g/g) similar to those achieved when using the general
      medium for Lactobacilli (18.6 g/L, 1.11 g/L.h, and 0.62 g/g, respectively) or
      lees without TA extraction (16.4-17.2 g/L, 0.96-1.21 g/L.h, and 0.61-0.66 g/g,
      respectively). This technology not only avoids pollutant disposal but also
      represents a commercial source of tartaric acid and economic nutrients for
      biotechnological processes.

PMID- 17002470
TI  - Treatment of mcf-7 breast cancer cells with a red grape wine polyphenol fraction
      results in disruption of calcium homeostasis and cell cycle arrest causing
      selective cytotoxicity.
AB  - Food components influence the physiology by modulating gene expression and
      biochemical pathways within the human body. The disease-preventive roles of
      several fruit and vegetable components have been related to such properties.
      Polyphenolic components such as flavonoids are strong antioxidants and induce the
      expression of several xenobiotic-detoxifying enzymes. The mechanism of selective
      cytotoxicity induced by red grape wine polyphenols against MCF-7 breast cancer
      cells was investigated in relation to their interference with calcium
      homeostasis. MCF-7 cells showed an increase in cytosolic calcium levels within 10
      min of treatment with the polyphenols. Immunohistochemical localization of
      calmodulin with secondary gold-labeled antibodies showed similar levels of gold
      labeling in both MCF-7 cells and the spontaneously immortalized, normal MCF-10A
      cell line. MCF-7 cells treated with the red wine polyphenol fraction (RWPF)
      showed swelling of endoplasmic reticulum, dissolution of the nucleus, and loss of
      plasma membrane integrity as well as reduced mitochondrial membrane potential.
      These cells were arrested at the G2/M interphase. By contrast, MCF-10A cells did
      not show such changes after RWPF treatment. The results suggest that polyphenol
      induced calcium release may disrupt mitochondrial function and cause membrane
      damage, resulting in selective cytotoxicity toward MCF-7 cells. This property
      could further be developed toward breast cancer prevention strategies either
      independently or in conjunction with conventional prevention therapies where a
      positive drug-nutrient interaction can be demonstrated.

PMID- 17002471
TI  - Iron uptake by Caco-2 cells from NaFeEDTA and FeSO4: Effects of ascorbic acid,
      pH, and a Fe(II) chelating agent.
AB  - Sodium iron(III) ethylenediaminetetraacetate (NaFeEDTA) has considerable promise
      as an iron fortificant because of its high bioavailability in foods containing
      iron absorption inhibitors. In this study, uptakes of iron from NaFeEDTA, FeSO4,
      and FeCl3 by Caco-2 cells were compared in the absence or presence of ascorbic
      acid (AA), an iron absorption enhancer; at selected pH levels; and in the absence
      or presence of an iron absorption inhibitor, bathophenanthroline disulfonic acid
      (BPDS). Ferritin formation in the cells was used as the indicator of iron uptake.
      Uptake from all three Fe sources was similar in the absence of AA. Adding AA at a
      5:1 molar excess as compared to Fe increased uptake by 5.4-, 5.1-, and 2.8-fold
      for FeSO4, FeCl3, and NaFeEDTA, respectively. The smaller effect of AA on uptake
      from NaFeEDTA may be related to the higher solubility of NaFeEDTA and/or the
      strong binding affinity of EDTA for Fe3+, which may prevent AA and duodenal
      cytochrome b from effectively reducing EDTA-bound Fe. Uptake was inversely
      related to the pH of the media over a range of 5.8-7.2. Because uptake by DMT-1
      is proton-coupled, the inverse relationship between pH and Fe uptake in all three
      iron sources suggests that they all follow the DMT-1 pathway into the cell.
      Adding BPDS to the media inhibited uptake from all three iron compounds equally.
      Because BPDS binds Fe2+ but not Fe3+ and because only Fe2+ is transported by DMT
      1, the finding that BPDS inhibited uptake from NaFeEDTA suggests that at least
      some iron dissociates from EDTA and is reduced just as simple inorganic iron at
      the brush border membrane of the enterocyte. Taken together, these results
      suggest that uptake of iron from NaFeEDTA by intestinal enterocytes is regulated
      similarly to uptake from iron salts.

PMID- 17002472
TI  - Iron dissociates from the NaFeEDTA complex prior to or during intestinal
      absorption in rats.
AB  - Sodium iron ethylenediaminetetraacetate (NaFeEDTA) has superior iron
      bioavailability especially in foods containing iron absorption inhibitors.
      However, mechanisms involved in the absorption and subsequent partitioning of
      iron complexed with EDTA are poorly understood. Our objectives were to compare
      retention and tissue distribution of iron administered to rats either as FeSO4 or
      NaFeEDTA, either orally (OR) or subcutaneously (SC). Weanling rats were fed
      semipurified diets supplemented with either FeSO4 or NaFeEDTA for 7 days. They
      were then given a meal containing 59Fe-labeled FeSO4 or NaFeEDTA, or they were
      injected SC with these two forms of radiolabeled Fe. 59Fe retention was measured
      by whole body counting. Urine was collected and counted at 24 h intervals
      throughout the counting period. Tissue samples were analyzed for nonheme iron and
      59Fe activity. Absorption of iron from FeSO4 or NaFeEDTA was similar (57.7 and
      53.4%, respectively). Seventy-seven percent of the injected Na59FeEDTA was
      excreted in the urine within 24 h, whereas only 0.5, 0.8, and 1.4% of the
      injected 59FeSO4, oral 59FeSO4, and oral Na59FeEDTA, respectively, was excreted
      in the urine. The nonheme iron content was lower in the liver and spleen, by 56.8
      and 28.4%, respectively, among rats consuming the NaFeEDTA diet as compared to
      rats fed FeSO4. We conclude that iron is dissociated from EDTA prior to or during
      intestinal absorption and that some fraction of the dissociated EDTA is absorbed
      separately from the iron.

PMID- 17002473
TI  - Dietary conjugated linoleic acid lowered tumor necrosis factor-alpha content and
      altered expression of genes related to lipid metabolism and insulin sensitivity
      in the skeletal muscle of Zucker rats.
AB  - Type-2 diabetes is characterized by obesity-related insulin resistance. Insulin
      resistance and accompanying hyperinsulinemia have been reported to play an
      important role in pathogenesis of the metabolic syndrome. Conjugated linoleic
      acid (CLA), a mixture of positional and geometric isomers of linoleic acid, has
      attracted considerable attention because of its potentially beneficial biological
      effects. Previous studies showed that dietary CLA alleviates diabetes through
      improvement of glucose tolerance and insulin-stimulated glucose transport
      activity in skeletal muscle of diabetic rats. Skeletal muscle plays an important
      role both in insulin-mediated glucose metabolism and in lipid metabolism. In the
      present study, we evaluated comprehensively the effect of dietary CLA on the
      expression of genes related to lipid metabolism and insulin sensitivity in the
      skeletal muscle of obese, diabetic Zucker rats. After 8 weeks of feeding,
      expression of lipogenic genes was decreased in tendency, while expression of
      lipolytic genes was markedly increased by dietary CLA. Additionally, expression
      of genes-related insulin sensitivity, such as adiponectin receptor 1, was
      significantly enhanced, and mRNA level of peroxisome proliferator activated
      receptor-alpha, known as a transcriptional factor related lipid metabolism and
      insulin signaling in skeletal muscle, was markedly increased in CLA-fed rats. We
      also showed that dietary CLA significantly decreased the level of tumor necrosis
      factor-alpha (TNF-alpha), associated with the development of insulin resistance,
      in the skeletal muscle of Zucker rats. We suppose that the attenuated TNF-alpha
      accumulation in skeletal muscle may contribute to the alteration of expression of
      several genes and the alleviation of insulin resistance in CLA-fed Zucker rats.

PMID- 17002474
TI  - Anthocyanin absorption and antioxidant status in pigs.
AB  - The effect of a simultaneous intake of food or flavonoids on anthocyanins
      absorption and antioxidant status in pigs was investigated. Twelve male pigs at
      27.1 +/- 0.7 kg BW fitted with jugular venous cannulae were maintained in
      individual metabolic crates. The animals were each given one of three dietary
      treatments in random order: blackcurrant powder (BC) to give a dose of 100 mg
      total ACNs/kg BW mixed either with water and sugar (Diet A), cereal (Weet-Bix),
      milk, and sugar (Diet B), or cereal, milk, sugar, and an additional flavonol
      (rutin, approximately 100 mg/kg BW) (Diet C). The four major anthocyanins of BC,
      delphinidin-3-glucoside, delphinidin-3-rutinoside, cyanidin-3-glucoside, and
      cyanidin-3-rutinoside, were identified and quantified by HPLC-PDA in all three
      diets. In the pig plasma, four peaks with a reversed pattern to those of
      anthocyanins in the BC extract were detected. The total amount of anthocyanins
      absorbed was not significantly different between the three diets, but the rate of
      absorption and subsequent decline was slower following administration of diet B
      and C than diet A. All three diets increased antioxidant capacity when measured
      by the FRAP assay but not when measured by the ORAC and non-protein ORAC assay.
      However, the increase was delayed and did not appear until 4 h after ingestion,
      at a time when plasma anthocyanin levels had returned to baseline. The present
      study demonstrates that the simultaneous intake of food or other flavonoids
      delays the absorption profile for anthocyanins. Our results also suggest that the
      increase in antioxidant capacity is not due to dietary anthocyanins but may be
      due to metabolites that result from anthocyanin consumption.

PMID- 17002475
TI  - Determination of isopropyl thioxanthone (ITX) in fruit juices by pressurized
      liquid extraction and liquid chromatography-mass spectrometry.
AB  - A rapid LC-MS method, which compares different mass analyzers-single quadrupole,
      ion trap, and triple quadrupole-was developed for the quantitative determination
      of isopropyl thioxanthone (ITX) in fruit juices. ITX, a photoinitiator in UV
      cured inks that can reach foods from the cartons for beverages in which they are
      used, was extracted from fruit juice samples with acetone/hexane (50:50) using
      pressurized liquid extraction. This method gave detection limits of 3, 3, and
      0.01 microg/L and quantification limits of 10, 10, and 0.05 microg/L using single
      quadrupole, ion trap, and triple quadrupole, respectively. Five replicate
      fortifications of different fruit juices at the quantification limit gave
      recoveries oscillating between 68 and 72% with CV varying between 14 and 18%.
      This is the first report of a positive mass spectrometric identification and
      quantification of ITX in fruit juice samples packed in TetraPack. The sensitivity
      and specificity of the LC-MS/MS analysis using the triple quadrupole enables it
      to be the method of choice for risk assessment and monitoring. The method was
      applied to apricot, orange, peach, apple, grape and pineapple, and cherry and
      strawberry juices and to fruit nectars from Spain and Italy, and the ITX was
      detected in the range of 0.05-0.78 microg/L.

PMID- 17002476
TI  - The generalisability of pharmacoeconomic studies: issues and challenges ahead.
AB  - Developing from a previous review, this article revisits the generalisability
      theme to summarise recent advances in methodology and provide an update of
      challenges faced by producers and users of pharmacoeconomic data. Our original
      evaluative criteria encompassed technical issues, applicability and
      transferability. The technical elements of best practice are comparatively
      uncontroversial: choosing relevant alternatives; transparent reporting of methods
      and findings; accessing and applying the best-quality evidence; using best
      methods to synthesise data; and using deterministic sensitivity analysis to
      explore potential systematic bias whilst employing probabilistic sensitivity
      analysis to explore the influence of random error at the whole model level. The
      applicability of economic findings within their original policy context (e.g.
      national analyses based on generalisable within-country data) can be determined,
      provided that best practice guidelines for economic modelling are adhered to. The
      transferability of economic findings (from one policy setting to another, e.g.
      country, region, clinical setting or patient population) requires careful
      exploration of changes in resource implications, unit prices and outcomes, a
      process facilitated again by transparent reporting of methods, adjustment for
      baseline risk and potentially by recent statistical developments intended to deal
      with hierarchically structured data. Although there is considerable consensus in
      the published literature about these key issues, limitations remain for economic
      analysis as implemented because of its opaqueness of method, failure to reflect
      the opportunity cost of decisions and lack of societal mandate. If the primary
      purpose of health economic evaluation is to help society to obtain the best value
      from limited resources, then, at a time when most technologically advanced
      societies need to engage with the realities of limited healthcare funding,
      technocratic solutions alone appear insufficient. Making health economic findings
      accessible to patients, clinicians and society, in the form of relevant
      narratives, will help this essential debate and expose assumptions underpinning
      economic analysis to broader critical inspection.

PMID- 17002477
TI  - QALYs: are they helpful to decision makers?
AB  - The QALY is the product of life expectancy (estimated in years) and its quality
      over that time (estimated in utilities or QOL units). It theoretically enables
      direct comparison of the costs of obtaining different health outcomes through
      cost utility analysis (CUA). In this review, we argue that, at present, the
      problems related to the use of utilities preclude the use of cost per QALY as a
      major determinant of policy decisions on the acquisition and use of health
      technologies. Those who use CUA can be divided into (i) those who inform the
      process of decision making through CUA and (ii) those who make the decisions. The
      former have no direct budgetary responsibility for the decisions that are taken,
      while the decision makers must pay for those decisions from their budgets. Use of
      CUA rests on the assumption that all QALYs are of equivalent value in the eyes of
      society. However, the value accorded to them varies with circumstances. The
      utilities or QOL indices required to compute QALYs can be measured in different
      ways, which give different answers, and have been shown to be unreliable. Thus,
      the QALY is not sufficiently accurate or reliable to be used by decision makers
      as a basis for comparison of the costs of different technologies. Until the
      theoretical and practical problems of determining health preferences are resolved
      and the methods of their measurement are standardised, it is necessary to
      estimate the cost effectiveness of health interventions by relating their cost to
      their primary health outcomes.

PMID- 17002478
TI  - Should we abandon QALYs as a resource allocation tool?

PMID- 17002479
TI  - Therapeutic options for the prevention and treatment of postoperative nausea and
      vomiting: a pharmacoeconomic review.
AB  - Even with the development of the serotonin 5-HT(3) receptor antagonists in recent
      years, postoperative nausea and vomiting (PONV) remains a significant concern for
      clinicians and patients. For the selection of an appropriate antiemetic strategy
      for PONV, economic considerations should be taken into account. A literature
      search covering the period from September 1996 to August 2005 yielded 16 economic
      evaluations on antiemetics used for the prevention or treatment of PONV. In these
      studies, a variety of different antiemetic regimens were evaluated, with
      different doses and timing of administration, in many different populations, for
      various types of surgery, and in different settings. In addition, there were many
      differences in the design of these economic evaluations in terms of the extent of
      the costs considered and the decision rules used when forming conclusions.
      Therefore, despite the availability of economic evaluations on antiemetics in
      PONV, it is difficult to draw clear conclusions with such disparate information.
      In spite of these limitations, key learning can be drawn from these economic
      evaluations. From studies where a placebo was used as a comparator, we can
      conclude that there is clinical benefit in using an antiemetic for the prevention
      of PONV versus no therapy. The dose of the 5-HT(3) receptor antagonist seems more
      important in determining cost effectiveness than the selection of the agent
      itself, and less expensive agents such as droperidol, dexamethasone and
      prochlorperazine may also represent cost-effective alternatives to 5-HT(3)
      receptor antagonists. In an additional six studies where a willingness to pay
      (WTP) to avoid or reduce the incidence of PONV was estimated, the average WTP
      amounts varied from $US29 to $US117. Many questions remain unanswered about the
      cost effectiveness of existing antiemetics and their regimens, and little is
      known about the impact of new agents, such as the neurokinin-1 receptor
      antagonists, in the control of PONV.

PMID- 17002480
TI  - Single-inhaler combination therapy for asthma: a review of cost effectiveness.
AB  - Clinical studies have shown that the combination of an inhaled corticosteroid
      (ICS) and a long-acting beta(2)-adrenoceptor agonist (LABA) for patients with
      asthma is more effective than the use of ICS alone in equivalent or higher doses,
      as well as the use of other combinations. However, the relatively higher
      acquisition costs for the combination therapy require assessment of the value of
      the incremental costs, especially from a societal perspective. This review
      provides an overall assessment of the cost effectiveness of ICS plus LABA
      combination therapy for asthma. A systematic literature research was conducted in
      MEDLINE to identify studies published between January 1994 and September 2005.
      Cost-effectiveness studies derived from 11 clinical studies were identified. The
      ICS plus LABA combination was compared with ICS alone in eight studies, ICS plus
      a leukotriene antagonist in two studies, and a leukotriene antagonist alone in
      one study. All studies focused on measuring direct medical costs in a total of
      six different healthcare systems, and three studies conducted sensitivity
      analyses, including productivity costs. Outcomes were measured in treatment
      success (changes in lung function), episode-free days, and symptom-free days by
      evaluating short-term follow-up. The combination of ICS and LABA was found to be
      more efficacious and cost effective compared with ICS alone or alternative
      combinations of controller medications. Further considerations for measuring long
      term outcomes and dose-response relationships might be required to provide
      further evidence on the cost effectiveness of combination therapy with ICS plus
      LABA.

PMID- 17002481
TI  - Disability and quality of life in post-traumatic stress disorder: impact of drug
      treatment.
AB  - The degree of functional disability and quality of life (QOL) impairment in
      patients with post-traumatic stress disorder (PTSD) is at least comparable with,
      and in many instances greater than, that of patients with other anxiety and mood
      disorders. Multidimensional QOL assessments in PTSD have utility in capturing
      aspects of individual patient experience and satisfaction related to health and
      treatment, and have fairly robust sensitivity to treatment effects. Despite the
      growing number of epidemiological and clinical studies detailing QOL in PTSD,
      there are few studies of the impact of pharmacological agents on QOL outcomes,
      and none that have included an economic component to evaluate the resource
      consequences of the disorder. To date, the selective serotonin reuptake
      inhibitors have been shown to confer significant acute (and longer term) QOL and
      psychosocial benefits. Further investigation of the relationship of QOL to PTSD
      symptom severity, disability, treatment outcome and cost, among the different
      drug treatment modalities, is clearly needed.

PMID- 17002482
TI  - Hospitalisation costs of cystic fibrosis.
AB  - OBJECTIVE: To calculate per-case hospital costs for patients with cystic fibrosis
      under routine conditions from a healthcare provider's perspective; identify the
      impact of different cost categories; investigate whether cases with cystic
      fibrosis can be grouped into homogenous cost groups according to defined severity
      levels; and determine the value of specific factors as predictors of hospital
      cost variations. METHODS: All data were collected from cases (n = 131) admitted
      to an inpatient cystic fibrosis unit under routine conditions during a period of
      6 months in 2004. All costs were calculated for the year 2004 and divided into
      categories with high and low impact on variation in hospitalisation costs between
      patients. Staff costs for patient care, laboratory costs and drug costs were
      defined as categories with high impact, thus the individual resource utilisation
      for each case was measured. Cost categories that were classified as having a low
      impact were measured as overhead costs. Cases were classified according to two
      different severity models; within each model, patients were classified according
      to three severity levels. The diagnosis-related model classifies patients with
      pulmonary hypertension and global respiratory insufficiency as having severe
      disease, patients with Pseudomonas aeruginosa as having moderate disease, and
      patients with no colonisation of the lungs as having mild disease. The lung
      function-related model differentiates patients as having mild, moderate and
      severe disease when patients have forced expiratory volumes in 1 second (FEV(1))
      that are > or =70%, between > or =40% and <70%, and <40%, respectively. Analysis
      of variance tests were performed to investigate the differences of mean costs
      between the groups. Ordinary least squares regression analysis was used to
      determine predictors for cost variation. RESULTS: The mean total costs per case
      were 7326 euro. Almost one-third of the total mean costs were attributable to
      drug costs (28% of total costs), while shares of staff costs for patient care and
      laboratory costs (both 9% of total costs) were relatively small. Most of the
      difference in costs between severity levels was attributable to the variation in
      overhead costs and drug costs. For both severity models differences in mean total
      costs of mild and severe cases were statistically significant (p < 0.01 and p <
      0.05, respectively) when compared with the mean costs of non-mild and non-severe
      cases. However, in moderate cases, significant differences compared with cases
      that were not of moderate severity were only seen for certain cost categories. In
      the multiple regression model the variables 'diagnosis-related severity' and
      'FEV(1)' explained 31% of the variance of 'Ln (total costs per case)' between
      severity levels (p < or = 0.01). CONCLUSION: This study shows that to a large
      extent hospitalisation costs for patients with cystic fibrosis vary according to
      the severity of their disease; drug costs play a major role in these differences.
      In the light of this variation it seems plausible to create separate
      reimbursement rates for two or three severity groups. Diagnoses as well as FEV(1)
      seem suitable criteria for such a classification.

PMID- 17002483
TI  - The initial validation of a Markov model for the economic evaluation of (new)
      treatments for rheumatoid arthritis.
AB  - OBJECTIVE: Markov models are increasingly used in economic evaluations of (new)
      treatments for chronic diseases. In this study we propose a Markov model with
      health states defined by the disease activity score (DAS) to be used to
      extrapolate efficacy data from short-term clinical trials in rheumatoid arthritis
      to longer term cost-effectiveness results. Moreover, we perform an initial
      validation of this model. METHODS: To test the validity of the model, the
      expected disease course (according to the model) was first compared with the
      observed disease course in an inception cohort of newly diagnosed rheumatoid
      arthritis patients. Then the relationship of the health states with utility and
      costs was investigated. Finally, costs and QALYs were calculated for usual care
      of patients in the first 5 years of their disease using the model and compared
      with the literature. RESULTS: The model seemed to be able to extrapolate 1-year
      efficacy data as seen by a comparable distribution over the Markov states between
      the model results and the observational data. The health states had a significant
      relationship with costs and utility, and population characteristics had only a
      moderate effect on the cost and utility values of the Markov states. The
      distribution over the Markov states resulted in 3.266 expected QALYs per patient
      over 5 years. The expected medical and total costs per patient over 5 years were
      6754 euro (1997 values) and 12,641 euro, respectively, for standard rheumatoid
      arthritis care in The Netherlands. CONCLUSION: The developed Markov model seems a
      valid model for use in economic evaluations in rheumatoid arthritis. The model
      produced similar utilities, but lower total costs, to those in previously
      published studies. Although the steps to develop and validate this Markov model
      were applied in the context of rheumatoid arthritis, they can be generalised to
      other chronic diseases.

PMID- 17002484
TI  - The cost effectiveness of anticoagulation management services for patients with
      atrial fibrillation and at high risk of stroke in the US.
AB  - BACKGROUND: Anticoagulation therapy with warfarin is widely considered the
      standard of care for stoke prophylaxis in patients with atrial fibrillation who
      are at high risk of stroke. Community-based studies in the US have reported that
      the effectiveness of anticoagulation varies by management approach and that
      patients receiving warfarin have international normalised ratio (INR) values
      within the target therapeutic range less than half the time. OBJECTIVE: To
      estimate the lifetime societal costs and health benefits of warfarin therapy to
      prevent strokes, specifically in elderly patients (mean age 70 years) with atrial
      fibrillation who are at high risk of stroke, when anticoagulation is managed
      through usual care versus anticoagulation management services, where dedicated
      anticoagulation professionals (e.g. physician or pharmacist) monitor and oversee
      patients. METHODS: Semi-Markov decision model with a 30-day cycle length and 10
      year time horizon (to reflect the mean life expectancy of the study population).
      Univariate sensitivity analyses and Bayesian second-order multivariate
      probabilistic sensitivity analysis using Monte Carlo simulation were performed.
      Outcomes measures were costs and QALYs. Most of the probability and outcome
      estimates included were derived from the recent SPORTIF (Stroke Prevention using
      ORal Thrombin Inhibitor in atrial Fibrillation) V trial. Utility values were
      derived from a large, nationally representative sample of individuals in the
      Medical Expenditure Panel Survey and were adjusted for age, sex, race, ethnicity,
      income, education and co-morbidity. Resource utilisation was based on experience
      at the University Medicine Group Practice Anticoagulation Clinic (University of
      Colorado, Denver, CO, USA) and costs ($US; 2004 values) included were for
      warfarin and aspirin (acetylsalicylic acid) use and those associated with major
      bleeding, treatment of primary events, routine INR and biochemistry monitoring,
      ECGs, and clinic visits. Costs and outcomes were discounted by 3% per annum.
      RESULTS: The anticoagulation management service improved effectiveness by 0.057
      (95% credible interval 0, 0.36) QALYs and reduced costs by $US2100 (95% credible
      interval -$US19,800, $US300) [2004 values] compared with usual care. Results were
      sensitive to the extent of the increase in risk of primary events (all strokes
      and systemic embolic events attributable to usual care, but were robust to
      variation in other input variables). The anticoagulation management service was
      the dominant strategy in 91% of Monte Carlo simulations. CONCLUSION: The
      anticoagulation management service appears to cost less and provide greater
      effectiveness than usual care. To enhance stroke prophylaxis among high-risk
      patients with atrial fibrillation, physicians and Medicare plans may wish to
      consider augmenting 'usual care' by the addition of patient-monitoring technology
      strategies such as formally organised anticoagulation monitoring programmes.

PMID- 17002485
TI  - Anticoagulation for stroke prevention: high effectiveness, more cost benefit?

PMID- 17002486
TI  - Oxyntomodulin : a novel potential treatment for obesity.
AB  - The prevalence of obesity is increasing rapidly and the associated morbidity and
      mortality has led to an urgent need for potential therapeutic targets to reduce
      appetite and food intake. Gut hormones released after eating that coordinate
      digestive activity and promote satiety are novel potential treatments for
      obesity. Oxyntomodulin is a gut hormone that is produced by the L cells in the
      small intestine and reduces food intake. It is timely to review some of the
      original literature on oxyntomodulin, to evaluate what is already known about the
      peptide, and also to set the recent findings on its effects on food intake and
      bodyweight into context.Recent studies have shown that long-term peripheral
      administration of oxyntomodulin to rats leads to reduced food intake and reduced
      weight gain. Studies in humans have demonstrated that acute administration
      reduces food intake by 19%. When given preprandially by subcutaneous injection
      three times daily, oxyntomodulin resulted in a reduction in food intake and mean
      weight loss of 2.8kg over 4 weeks. Oxyntomodulin thus represents a potential
      therapy for obesity.The mechanism of action of oxyntomodulin is not known.
      Current evidence suggests that it acts via the glucagon-like peptide 1 (GLP-1)
      receptor. There may be an additional receptor in the gastric mucosa mediating its
      effects on gastric acid secretion. Although oxyntomodulin probably acts via the
      GLP-1 receptor, the two peptides differentially regulate food intake and energy
      expenditure in the mouse.Oxyntomodulin represents a potential therapy for
      obesity. Further work will help to clarify its mechanisms of action.

PMID- 17002487
TI  - The effectiveness of intensive glycemic control for the prevention of vascular
      complications in diabetes mellitus.
AB  - Obesity and type 2 diabetes mellitus have reached epidemic proportions in the US,
      and indeed, globally. While microvascular complications contribute to
      considerable morbidity, much of the excess mortality (around 70%) is due to
      macrovascular disease. Hyperglycemia has predictable toxic effects on multiple
      organs ('glucotoxicity') including the pancreas, where it impairs insulin
      secretion and insulin gene expression through mechanisms that lead to glucose
      densensitization and beta-cell exhaustion, eventually resulting in irreversible
      beta-cell failure. There is robust evidence to suggest that strict glycemic
      control reduces diabetic microvascular complications (retinopathy, nephropathy,
      and neuropathy) in both primary- and secondary-prevention settings. While
      unequivocal evidence that intensive glycemic control reduces the risk of death
      due to macrovascular disease is lacking, meta-analytic data and controlled
      clinical trial data suggest there may still be clinically significant lowering of
      the risk for macrovascular endpoints through strict glycemic control.
      Cardiovascular disease in a diabetic patient is a collusion of several factors
      besides hyperglycemia, such as hypertension, dyslipidemia, diffuse endothelial
      dysfunction, hypercoagulability, and inflammation. It is important to address
      lifestyle issues such as maintenance of ideal bodyweight, good dietary practice,
      smoking cessation, and regular exercise in the comprehensive risk management of a
      diabetic patient, in order to reduce the vascular complications. Large, ongoing
      clinical trials such as ACCORD (Action to Control Cardiovascular Risk in
      Diabetes) are likely to establish the potential benefits of glycemic control in
      preventing or postponing macrovascular complications of diabetes.

PMID- 17002488
TI  - Gonadotropin-releasing hormone analog therapy for central precocious puberty and
      other childhood disorders affecting growth and puberty.
AB  - Gonadotropin-releasing hormone (GnRH) analog therapy relies primarily on the
      ability of these compounds to bind to and modulate GnRH-receptor activity. GnRH
      analogs have been used in pediatric patients where endogenous gonadotropin
      release is undesirable or potentially harmful, such as in: (i) patients with
      central precocious puberty (CPP); (ii) healthy short children where pubertal
      delay would provide an opportunity to supplement pre-pubertal linear growth; and
      (iii) children with malignancies and other disorders where treatment requires the
      use of gonadotoxic compounds. In the first two groups of patients, GnRH agonists
      may be used alone or in conjunction with somatropin (growth hormone [GH]) to
      prevent early skeletal maturation and increase the subsequent adult height, while
      in the latter case, GnRH agonists are used alone or in conjunction with GnRH
      antagonists in an attempt to preserve gonadal function.In children and
      adolescents with CPP, timely use of GnRH agonists alone can result in an adult
      height within the genetic potential of the individual (target height); however,
      minimal height is gained when GnRH agonist therapy is commenced after a marked
      advancement of skeletal age. This provides the rationale for combined therapy
      with GnRH agonists and somatropin in such patients, and studies have shown
      improved growth with this approach compared with GnRH agonists alone. Combination
      therapy with GnRH agonists and somatropin has also been shown to increase adult
      heights to a greater extent than GnRH agonists alone in pediatric patients with
      concomitant CPP and GH deficiency, those with idiopathic short stature, and those
      born small for gestational age; however, such combination therapy has shown no
      increased benefit over somatropin alone in pediatric patients with GH deficiency.
      Limited results in children and adolescents with congenital adrenal hyperplasia
      and chronic primary hypothyroidism have also shown increased growth rates, while
      no growth benefit was seen in pediatric renal transplant recipients.GnRH analogs
      also have potential as gonadoprotective agents; studies of GnRH agonists used
      alone and in combination with GnRH antagonists in women undergoing cytotoxic
      therapy have shown increased preservation of reproductive potential in patients
      who were receiving GnRH analog therapy versus those who were not.The adverse
      effects of GnRH analogs mainly consist of menopausal-like complaints. Increases
      in bodyweight and body mass index in children receiving GnRH agonist therapy have
      been shown; however, these increases do not persist after discontinuation of
      therapy. Adult bone mineral density and fertility are also not adversely affected
      by childhood GnRH agonist therapy.GnRH analog therapy appears to be both well
      tolerated and effective in pediatric patients, as it allows the preservation or
      improvement of adult height, and shows no longstanding negative effects on body
      composition, bone density, reproductive function, or endocrine physiology. These
      agents may also be useful for preservation of gonadal function in children and
      adolescents undergoing cytotoxic therapy.

PMID- 17002489
TI  - Metabolic bone disease in children : etiology and treatment options.
AB  - Metabolic bone disease in children includes many hereditary and acquired
      conditions of diverse etiology that lead to disturbed metabolism of the bone
      tissue. Some of these processes primarily affect bone; others are secondary to
      nutritional deficiencies, a variety of chronic disorders, and/or treatment with
      some drugs. Some of these disorders are rare, but some present public health
      concerns (for instance, rickets) that have been well known for many years but
      still persist. The most important clinical consequences of bone metabolic
      diseases in the pediatric population include reduced linear growth, bone
      deformations, and non-traumatic fractures leading to bone pain, deterioration of
      motor development and disability. In this article, we analyze primary and
      secondary osteoporosis, rickets, osteomalacia (nutritional and hereditary vitamin
      D-dependent, hypophosphatemic and that due to renal tubular abnormalities), renal
      osteodystrophy, sclerosing bony disorders, and some genetic bone diseases
      (hypophosphatasia, fibrous dysplasia, skeletal dysplasia, juvenile Paget disease,
      familial expansile osteolysis, and osteoporosis pseudoglioma syndrome). Early
      identification and treatment of potential risk factors is essential for skeletal
      health in adulthood. In most conditions it is necessary to ensure an appropriate
      diet, with calcium and vitamin D, and an adequate amount of physical activity as
      a means of prevention. In secondary bone diseases, treatment of the primary
      disorder is crucial. Most genetic disorders await prospective gene therapies,
      while bone marrow transplantation has been attempted in other disorders. At
      present, affected patients are treated symptomatically, frequently by
      interdisciplinary teams. The role of exercise and pharmacologic therapy with
      calcium, vitamin D, phosphate, bisphosphonates, calcitonin, sex hormones, growth
      hormone, and thiazides is discussed. The perspectives on future therapy with
      insulin-like growth factor-1, new analogs of vitamin D, strontium,
      osteoprotegerin, and calcimimetics are presented.

PMID- 17002490
TI  - Oral paricalcitol.
AB  - black triangle An oral formulation of paricalcitol has been developed for the
      prevention and treatment of secondary hyperparathyroidism in patients with stage
      3 or 4 chronic kidney disease.black triangle Paricalcitol is a synthetic vitamin
      D analog that binds to the vitamin D receptor inducing suppression of parathyroid
      hormone (PTH) secretion.black triangle Oral paricalcitol was significantly more
      effective than placebo in treating secondary hyperparathyroidism in patients with
      stage 3 or 4 chronic kidney disease. In a pooled analysis of three well designed,
      24-week trials, two consecutive reductions from baseline in intact PTH levels of
      >/=30% were achieved by significantly more paricalcitol than placebo recipients
      (91% vs 13%).black triangle In addition, mean levels of the biochemical bone
      markers serum bone-specific alkaline phosphatase, serum osteocalcin, and urinary
      pyridinoline were reduced from baseline to a significantly greater extent with
      paricalcitol than with placebo, indicating a reduction in bone turnover.black
      triangle Oral paricalcitol was well tolerated; there was no significant
      difference between paricalcitol and placebo recipients in the incidence of
      hypercalcemia, hyperphosphatemia, or elevated calcium-phosphorus product.

PMID- 17002491
TI  - Oral paricalcitol : a viewpoint by keith C. Norris.

PMID- 17002492
TI  - Oral paricalcitol: a viewpoint by james B. Wetmore and L. Darryl quarles.

PMID- 17002493
TI  - Spotlight on inhaled human insulin (exubera((r))) in diabetes mellitus.
AB  - Inhaled human insulin (Exubera((R)) [insulin human (rDNA origin)] Inhalation
      Powder) has recently been approved in the EU and the US for preprandial use in
      adult patients with diabetes mellitus. This formulation of insulin has a more
      rapid onset, but similar duration, of glucose-lowering activity compared with
      subcutaneously administered regular human insulin.Preprandial inhaled human
      insulin provided glycemic control that was comparable to preprandial subcutaneous
      regular insulin when added to long- or intermediate-acting subcutaneous basal
      insulin in patients with type 1 diabetes. Inhaled human insulin is also effective
      when administered alone, when combined with oral antihyperglycemic therapy, or
      when combined with basal subcutaneous insulin in patients with type 2 diabetes.
      Comparable rates of hypoglycemia occurred in patients treated with inhaled human
      insulin and in those treated with subcutaneous regular human insulin. Patients
      treated with inhaled human insulin demonstrated a greater decline in pulmonary
      function (forced expiratory volume in 1 second, carbon monoxide diffusing
      capacity) than patients treated with comparator antihyperglycemic agents; the
      mean difference between the treatment groups that favored the comparators was
      noted within the first several weeks of treatment, and did not change over a 2
      year treatment period. This agent has also been associated with significant
      improvements in some quality-of-life and treatment satisfaction scores,
      especially when compared with subcutaneous mealtime insulin regimens.

PMID- 17002494
TI  - Computational model of vascular endothelial growth factor spatial distribution in
      muscle and pro-angiogenic cell therapy.
AB  - Members of the vascular endothelial growth factor (VEGF) family of proteins are
      critical regulators of angiogenesis. VEGF concentration gradients are important
      for activation and chemotactic guidance of capillary sprouting, but measurement
      of these gradients in vivo is not currently possible. We have constructed a
      biophysically and molecularly detailed computational model to study
      microenvironmental transport of two isoforms of VEGF in rat extensor digitorum
      longus skeletal muscle under in vivo conditions. Using parameters based on
      experimental measurements, the model includes: VEGF secretion from muscle fibers;
      binding to the extracellular matrix; binding to and activation of endothelial
      cell surface VEGF receptors; and internalization. For 2-D cross sections of
      tissue, we analyzed predicted VEGF distributions, gradients, and receptor
      binding. Significant VEGF gradients (up to 12% change in VEGF concentration over
      10 mum) were predicted in resting skeletal muscle with uniform VEGF secretion,
      due to non-uniform capillary distribution. These relative VEGF gradients were not
      sensitive to extracellular matrix composition, or to the overall VEGF expression
      level, but were dependent on VEGF receptor density and affinity, and
      internalization rate parameters. VEGF upregulation in a subset of fibers
      increased VEGF gradients, simulating transplantation of pro-angiogenic myoblasts,
      a possible therapy for ischemic diseases. The number and relative position of
      overexpressing fibers determined the VEGF gradients and distribution of VEGF
      receptor activation. With total VEGF expression level in the tissue unchanged,
      concentrating overexpression into a small number of adjacent fibers can increase
      the number of capillaries activated. The VEGF concentration gradients predicted
      for resting muscle (average 3% VEGF/10 mum) is sufficient for cellular sensing;
      the tip cell of a vessel sprout is approximately 50 mum long. The VEGF gradients
      also result in heterogeneity in the activation of blood vessel VEGF receptors.
      This first model of VEGF tissue transport and heterogeneity provides a platform
      for the design and evaluation of therapeutic approaches.

PMID- 17002495
TI  - Sampling realistic protein conformations using local structural bias.
AB  - The prediction of protein structure from sequence remains a major unsolved
      problem in biology. The most successful protein structure prediction methods make
      use of a divide-and-conquer strategy to attack the problem: a conformational
      sampling method generates plausible candidate structures, which are subsequently
      accepted or rejected using an energy function. Conceptually, this often
      corresponds to separating local structural bias from the long-range interactions
      that stabilize the compact, native state. However, sampling protein conformations
      that are compatible with the local structural bias encoded in a given protein
      sequence is a long-standing open problem, especially in continuous space. We
      describe an elegant and mathematically rigorous method to do this, and show that
      it readily generates native-like protein conformations simply by enforcing
      compactness. Our results have far-reaching implications for protein structure
      prediction, determination, simulation, and design.

PMID- 17002497
TI  - Genomic convergence toward diploidy in Saccharomyces cerevisiae.
AB  - Genome size, a fundamental aspect of any organism, is subject to a variety of
      mutational and selection pressures. We investigated genome size evolution in
      haploid, diploid, and tetraploid initially isogenic lines of the yeast
      Saccharomyces cerevisiae. Over the course of approximately 1,800 generations of
      mitotic division, we observed convergence toward diploid DNA content in all
      replicate lines. This convergence was observed in both unstressful and stressful
      environments, although the rate of convergence was dependent on initial ploidy
      and evolutionary environment. Comparative genomic hybridization with microarrays
      revealed nearly euploid DNA content by the end of the experiment. As the
      vegetative life cycle of S. cerevisiae is predominantly diploid, this experiment
      provides evidence that genome size evolution is constrained, with selection
      favouring the genomic content typical of the yeast's evolutionary past.

PMID- 17002496
TI  - Role of AmiA in the morphological transition of Helicobacter pylori and in immune
      escape.
AB  - The human gastric pathogen Helicobacter pylori is responsible for peptic ulcers
      and neoplasia. Both in vitro and in the human stomach it can be found in two
      forms, the bacillary and coccoid forms. The molecular mechanisms of the
      morphological transition between these two forms and the role of coccoids remain
      largely unknown. The peptidoglycan (PG) layer is a major determinant of bacterial
      cell shape, and therefore we studied H. pylori PG structure during the
      morphological transition. The transition correlated with an accumulation of the N
      acetyl-D-glucosaminyl-beta(1,4)-N-acetylmuramyl-L-Ala-D-Glu (GM-dipeptide) motif.
      We investigated the molecular mechanisms responsible for the GM-dipeptide motif
      accumulation, and studied the role of various putative PG hydrolases in this
      process. Interestingly, a mutant strain with a mutation in the amiA gene,
      encoding a putative PG hydrolase, was impaired in accumulating the GM-dipeptide
      motif and transforming into coccoids. We investigated the role of the
      morphological transition and the PG modification in the biology of H. pylori. PG
      modification and transformation of H. pylori was accompanied by an escape from
      detection by human Nod1 and the absence of NF-kappaB activation in epithelial
      cells. Accordingly, coccoids were unable to induce IL-8 secretion by AGS gastric
      epithelial cells. amiA is, to our knowledge, the first genetic determinant
      discovered to be required for this morphological transition into the coccoid
      forms, and therefore contributes to modulation of the host response and
      participates in the chronicity of H. pylori infection.

PMID- 17002498
TI  - Adenomatous polyposis coli (APC) is required for normal development of skin and
      thymus.
AB  - The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt
      signaling pathway that is involved in development and tumorigenesis. Heterozygous
      knockout mice for Apc have a tumor predisposition phenotype and homozygosity
      leads to embryonic lethality. To understand the role of Apc in development we
      generated a floxed allele. These mice were mated with a strain carrying Cre
      recombinase under the control of the human Keratin 14 (K14) promoter, which is
      active in basal cells of epidermis and other stratified epithelia. Mice
      homozygous for the floxed allele that also carry the K14-cre transgene were
      viable but had stunted growth and died before weaning. Histological and
      immunochemical examinations revealed that K14-cre-mediated Apc loss resulted in
      aberrant growth in many ectodermally derived squamous epithelia, including hair
      follicles, teeth, and oral and corneal epithelia. In addition, squamous
      metaplasia was observed in various epithelial-derived tissues, including the
      thymus. The aberrant growth of hair follicles and other appendages as well as the
      thymic abnormalities in K14-cre; Apc(CKO/CKO) mice suggest the Apc gene is
      crucial in embryonic cells to specify epithelial cell fates in organs that
      require epithelial-mesenchymal interactions for their development.

PMID- 17002499
TI  - Meiotic chromosome synapsis-promoting proteins antagonize the anti-crossover
      activity of sgs1.
AB  - Sgs1, the budding yeast homolog of the mammalian BLM helicase, has been
      implicated in preventing excess recombination during both vegetative growth and
      meiosis. Most meiotic crossover (CO) recombination requires full function of a
      set of yeast proteins (Zip1, Zip2, Zip3, Zip4/Spo22, Mer3, Msh4, and Msh5, termed
      the SIC or ZMM proteins) that are also required for homologous chromosome
      synapsis. We report here genetic and molecular assays showing that sgs1 single
      mutants display relatively modest increases in CO recombination (less than 1.6
      fold relative to wild-type). In contrast, a much greater CO increase is seen when
      an sgs1 mutation is introduced into the CO- and synapsis-deficient zip1, zip2,
      zip3, mer3, or msh4 mutants (2- to 8-fold increase). Furthermore, close
      juxtaposition of the axes of homologous chromosomes is restored. CO restoration
      in the mutants is not accompanied by significant changes in noncrossover (NCO)
      recombinant frequencies. These findings show that Sgs1 has potent meiotic anti-CO
      activity, which is normally antagonized by SIC/ZMM proteins. Our data reinforce
      previous proposals for an early separation of meiotic processes that form CO and
      NCO recombinants.

PMID- 17002500
TI  - Two-stage two-locus models in genome-wide association.
AB  - Studies in model organisms suggest that epistasis may play an important role in
      the etiology of complex diseases and traits in humans. With the era of large
      scale genome-wide association studies fast approaching, it is important to
      quantify whether it will be possible to detect interacting loci using realistic
      sample sizes in humans and to what extent undetected epistasis will adversely
      affect power to detect association when single-locus approaches are employed. We
      therefore investigated the power to detect association for an extensive range of
      two-locus quantitative trait models that incorporated varying degrees of
      epistasis. We compared the power to detect association using a single-locus model
      that ignored interaction effects, a full two-locus model that allowed for
      interactions, and, most important, two two-stage strategies whereby a subset of
      loci initially identified using single-locus tests were analyzed using the full
      two-locus model. Despite the penalty introduced by multiple testing, fitting the
      full two-locus model performed better than single-locus tests for many of the
      situations considered, particularly when compared with attempts to detect both
      individual loci. Using a two-stage strategy reduced the computational burden
      associated with performing an exhaustive two-locus search across the genome but
      was not as powerful as the exhaustive search when loci interacted. Two-stage
      approaches also increased the risk of missing interacting loci that contributed
      little effect at the margins. Based on our extensive simulations, our results
      suggest that an exhaustive search involving all pairwise combinations of markers
      across the genome might provide a useful complement to single-locus scans in
      identifying interacting loci that contribute to moderate proportions of the
      phenotypic variance.

PMID- 17002502
TI  - Constitutive nucleosome depletion and ordered factor assembly at the GRP78
      promoter revealed by single molecule footprinting.
AB  - Chromatin organization and transcriptional regulation are interrelated processes.
      A shortcoming of current experimental approaches to these complex events is the
      lack of methods that can capture the activation process on single promoters. We
      have recently described a method that combines methyltransferase M.SssI treatment
      of intact nuclei and bisulfite sequencing allowing the representation of replicas
      of single promoters in terms of protected and unprotected footprint modules. Here
      we combine this method with computational analysis to study single molecule
      dynamics of transcriptional activation in the stress inducible GRP78 promoter. We
      show that a 350-base pair region upstream of the transcription initiation site is
      constitutively depleted of nucleosomes, regardless of the induction state of the
      promoter, providing one of the first examples for such a promoter in mammals. The
      350-base pair nucleosome-free region can be dissected into modules, identifying
      transcription factor binding sites and their combinatorial organization during
      endoplasmic reticulum stress. The interaction of the transcriptional machinery
      with the GRP78 core promoter is highly organized, represented by six major
      combinatorial states. We show that the TATA box is frequently occupied in the
      noninduced state, that stress induction results in sequential loading of the
      endoplasmic reticulum stress response elements, and that a substantial portion of
      these elements is no longer occupied following recruitment of factors to the
      transcription initiation site. Studying the positioning of nucleosomes and
      transcription factors at the single promoter level provides a powerful tool to
      gain novel insights into the transcriptional process in eukaryotes.

PMID- 17002501
TI  - Cell cycle-specified fluctuation of nucleosome occupancy at gene promoters.
AB  - The packaging of DNA into nucleosomes influences the accessibility of underlying
      regulatory information. Nucleosome occupancy and positioning are best
      characterized in the budding yeast Saccharomyces cerevisiae, albeit in
      asynchronous cell populations or on individual promoters such as PHO5 and GAL1
      10. Using FAIRE (formaldehyde-assisted isolation of regulatory elements) and
      whole-genome microarrays, we examined changes in nucleosome occupancy throughout
      the mitotic cell cycle in synchronized populations of S. cerevisiae. Perhaps
      surprisingly, nucleosome occupancy did not exhibit large, global variation
      between cell cycle phases. However, nucleosome occupancy at the promoters of cell
      cycle-regulated genes was reduced specifically at the cell cycle phase in which
      that gene exhibited peak expression, with the notable exception of S-phase genes.
      We present data that establish FAIRE as a high-throughput method for assaying
      nucleosome occupancy. For the first time in any system, nucleosome occupancy was
      mapped genome-wide throughout the cell cycle. Fluctuation of nucleosome occupancy
      at promoters of most cell cycle-regulated genes provides independent evidence
      that periodic expression of these genes is controlled mainly at the level of
      transcription. The promoters of G2/M genes are distinguished from other cell
      cycle promoters by an unusually low baseline nucleosome occupancy throughout the
      cell cycle. This observation, coupled with the maintenance throughout the cell
      cycle of the stereotypic nucleosome occupancy states between coding and non
      coding loci, suggests that the largest component of variation in nucleosome
      occupancy is "hard wired," perhaps at the level of DNA sequence.

PMID- 17002503
TI  - A Gambian infant with fever and an unexpected blood film.

PMID- 17002504
TI  - River blindness: a success story under threat?

PMID- 17002505
TI  - Was the "ABC" approach (abstinence, being faithful, using condoms) responsible
      for Uganda's decline in HIV?
AB  - BACKGROUND TO THE DEBATE: Uganda is one of the few African countries where rates
      of HIV infection have fallen, from about 15 percent in the early 1990s to about
      five percent in 2001. At the end of 2005, UNAIDS estimated that 6.7 percent of
      adults were infected with the virus. The reasons behind Uganda's success have
      been intensely studied in the hope that other countries can emulate the
      strategies that worked. Some researchers credit the success to the Ugandan
      government's promotion of "ABC behaviors"--particularly abstinence and fidelity.
      Uganda receives funds from the United States President's Emergency Plan for AIDS
      Relief, which promotes the ABC approach with a focus on abstinence-driven public
      health campaigns. Other researchers question whether the ABC approach was really
      responsible for the decline in HIV infection. Critics of the ABC approach also
      argue that by emphasizing abstinence over condom use, the approach leaves women
      at risk of infection, because in many parts of the world women are not empowered
      to insist on abstinence or fidelity.

PMID- 17002506
TI  - Why medical students should be trained in disaster management: our experience of
      the Kashmir earthquake.

PMID- 17002507
TI  - Is it just a marker for increased care?

PMID- 17002509
TI  - Were Eli Lilly unaware of this study?

PMID- 17002510
TI  - Crossing the language limitations.

PMID- 17002511
TI  - Are nonhuman primates good models for SARS?

PMID- 17002512
TI  - Snakebite: sociocultural anthropological bias.

PMID- 17002513
TI  - What guidelines? Never saw them!

PMID- 17002517
TI  - A conserved supergene locus controls colour pattern diversity in Heliconius
      butterflies.
AB  - We studied whether similar developmental genetic mechanisms are involved in both
      convergent and divergent evolution. Mimetic insects are known for their diversity
      of patterns as well as their remarkable evolutionary convergence, and they have
      played an important role in controversies over the respective roles of selection
      and constraints in adaptive evolution. Here we contrast three butterfly species,
      all classic examples of Mullerian mimicry. We used a genetic linkage map to show
      that a locus, Yb, which controls the presence of a yellow band in geographic
      races of Heliconius melpomene, maps precisely to the same location as the locus
      Cr, which has very similar phenotypic effects in its co-mimic H. erato.
      Furthermore, the same genomic location acts as a "supergene", determining
      multiple sympatric morphs in a third species, H. numata. H. numata is a species
      with a very different phenotypic appearance, whose many forms mimic different
      unrelated ithomiine butterflies in the genus Melinaea. Other unlinked colour
      pattern loci map to a homologous linkage group in the co-mimics H. melpomene and
      H. erato, but they are not involved in mimetic polymorphism in H. numata. Hence,
      a single region from the multilocus colour pattern architecture of H. melpomene
      and H. erato appears to have gained control of the entire wing-pattern
      variability in H. numata, presumably as a result of selection for mimetic
      "supergene" polymorphism without intermediates. Although we cannot at this stage
      confirm the homology of the loci segregating in the three species, our results
      imply that a conserved yet relatively unconstrained mechanism underlying pattern
      switching can affect mimicry in radically different ways. We also show that
      adaptive evolution, both convergent and diversifying, can occur by the repeated
      involvement of the same genomic regions.

PMID- 17002518
TI  - Food-web models predict species abundances in response to habitat change.
AB  - Plant and animal population sizes inevitably change following habitat loss, but
      the mechanisms underlying these changes are poorly understood. We experimentally
      altered habitat volume and eliminated top trophic levels of the food web of
      invertebrates that inhabit rain-filled leaves of the carnivorous pitcher plant
      Sarracenia purpurea. Path models that incorporated food-web structure better
      predicted population sizes of food-web constituents than did simple keystone
      species models, models that included only autecological responses to habitat
      volume, or models including both food-web structure and habitat volume. These
      results provide the first experimental confirmation that trophic structure can
      determine species abundances in the face of habitat loss.

PMID- 17002519
TI  - Implicit multisensory associations influence voice recognition.
AB  - Natural objects provide partially redundant information to the brain through
      different sensory modalities. For example, voices and faces both give information
      about the speech content, age, and gender of a person. Thanks to this redundancy,
      multimodal recognition is fast, robust, and automatic. In unimodal perception,
      however, only part of the information about an object is available. Here, we
      addressed whether, even under conditions of unimodal sensory input, crossmodal
      neural circuits that have been shaped by previous associative learning become
      activated and underpin a performance benefit. We measured brain activity with
      functional magnetic resonance imaging before, while, and after participants
      learned to associate either sensory redundant stimuli, i.e. voices and faces, or
      arbitrary multimodal combinations, i.e. voices and written names, ring tones, and
      cell phones or brand names of these cell phones. After learning, participants
      were better at recognizing unimodal auditory voices that had been paired with
      faces than those paired with written names, and association of voices with faces
      resulted in an increased functional coupling between voice and face areas. No
      such effects were observed for ring tones that had been paired with cell phones
      or names. These findings demonstrate that brief exposure to ecologically valid
      and sensory redundant stimulus pairs, such as voices and faces, induces specific
      multisensory associations. Consistent with predictive coding theories,
      associative representations become thereafter available for unimodal perception
      and facilitate object recognition. These data suggest that for natural objects
      effective predictive signals can be generated across sensory systems and proceed
      by optimization of functional connectivity between specialized cortical sensory
      modules.

PMID- 17002520
TI  - Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native
      plasma membranes.
AB  - Munc18-1, a protein essential for regulated exocytosis in neurons and
      neuroendocrine cells, belongs to the family of Sec1/Munc18-like (SM) proteins. In
      vitro, Munc18-1 forms a tight complex with the SNARE syntaxin 1, in which
      syntaxin is stabilized in a closed conformation. Since closed syntaxin is unable
      to interact with its partner SNAREs SNAP-25 and synaptobrevin as required for
      membrane fusion, it has hitherto not been possible to reconcile binding of Munc18
      1 to syntaxin 1 with its biological function. We now show that in intact and
      exocytosis-competent lawns of plasma membrane, Munc18-1 forms a complex with
      syntaxin that allows formation of SNARE complexes. Munc18-1 associated with
      membrane-bound syntaxin 1 can be effectively displaced by adding recombinant
      synaptobrevin but not syntaxin 1 or SNAP-25. Displacement requires the presence
      of endogenous SNAP-25 since no displacement is observed when chromaffin cell
      membranes from SNAP-25-deficient mice are used. We conclude that Munc18-1 allows
      for the formation of a complex between syntaxin and SNAP-25 that serves as an
      acceptor for vesicle-bound synaptobrevin and that thus represents an intermediate
      in the pathway towards exocytosis.

PMID- 17002521
TI  - Fluorescence of sunscreens adsorbed to dielectric nanospheres: parallels to
      optical behavior on hacat cells and skin.
AB  - Sunscreens applied to the skin are retained primarily in the stratum corneum,
      where they adsorb and act as a barrier preventing UV penetration to deeper
      layers. Photophysical properties of sunscreens have traditionally been studied
      either in solvents, which are very different from skin, or in skin or complex
      artificial skin systems, which are difficult to handle. The purpose of this study
      was to determine whether polystyrene nanospheres could serve as an improvement
      over solvents for evaluation of the photophysical properties of sunscreens
      without the presence of autofluorescence from and interactions with specific skin
      biomolecules. We used HaCat cells and excised skin for this comparative study
      with nanospheres. Fluorescence spectral properties of common hydrophobic
      sunscreens octyl salicylate, padimate O (2-ethylhexyl-4-dimethylaminobenzoate)
      and octyl methoxycinnamate adsorbed to 220 nm polystyrene spheres are similar to
      those of sunscreens adsorbed to HaCat cells and excised skin. Specifically,
      similarity in the emission peaks and their approximate positions, excitation peak
      positions and a measurable reduction in scattering upon sunscreen addition
      suggest that polystyrene nanospheres constitute a useful system to evaluate the
      photophysical properties of topical sunscreens and may serve as a model system
      for high-throughput evaluation of potential sunscreens. An unexpected result of
      this comparative study was the observation of an increase in a specific skin
      component emission caused by addition of padimate O.

PMID- 17002523
TI  - Input control processes in rapid serial visual presentations: target selection
      and distractor inhibition.
AB  - The attentional blink refers to the finding that the 2nd of 2 targets embedded in
      a stream of rapidly presented distractors is often missed. Whereas most theories
      of the attentional blink focus on limited-capacity processes that occur after
      target selection, the present work investigates the selection process itself.
      Identifying a target letter caused an attentional blink for the enumeration of
      subsequent dot patterns, but this blink was reduced when the dots shared their
      color with the target letter. In contrast, performance worsened when the color of
      the dots matched that of the remaining distractors in the stream. Similarity
      between the targets also affected competition between different sets of dots
      presented simultaneously within a single display. The authors conclude that the
      selection of targets from a rapid serial visual presentation stream is mediated
      by both excitatory and inhibitory attentional control mechanisms.

PMID- 17002522
TI  - Cryptochrome signaling in plants.
AB  - Cryptochromes are blue light receptors that mediate various light-induced
      responses in plants and animals. They share sequence similarity to photolyases,
      flavoproteins that catalyze the repair of UV light-damaged DNA, but do not have
      photolyase activity. Arabidopsis cryptochromes work together with the red/far-red
      light receptor phytochromes to regulate various light responses, including the
      regulation of cell elongation and photoperiodic flowering, and are also found to
      act together with the blue light receptor phototropins to mediate blue light
      regulation of stomatal opening. The signaling mechanism of Arabidopsis
      cryptochromes is mediated through negative regulation of COP1 by direct CRY-COP1
      interaction through CRY C-terminal domain. Arabidopsis CRY dimerized through its
      N-terminal domain and dimerization of CRY is required for light activation of the
      photoreceptor activity. Recently, significant progresses have been made in our
      understanding of cryptochrome functions in other dicots such as pea and tomato
      and lower plants including moss and fern. This review will focus on recent
      advances in functional and mechanism characterization of cryptochromes in plants.
      It is not intended to cover every aspect of the field; readers are referred to
      other review articles for historical perspectives and a more comprehensive
      understanding of this photoreceptor.

PMID- 17002524
TI  - Mechanical invariants are implicated in dynamic touch as a function of their
      salience in the stimulus flow.
AB  - The authors investigated the mechanical basis of length perception through
      dynamic touch using specially designed rods in which the various moments of mass
      distribution (mass, static moment, and rotational inertia) were varied
      independently. In a series of 4 experiments, exploration style and rod
      orientation were manipulated such that the relative salience of moments of mass
      distribution varied markedly. Results showed that perceived length was based on
      the most salient moments. The authors concluded that the notion of salience is
      crucial for understanding the implication of moments of mass distribution in
      length perception and that it should play a pivotal role in developing an
      encompassing theory of dynamic touch.

PMID- 17002525
TI  - Familiar interacting object pairs are perceptually grouped.
AB  - Identification of objects in a scene may be influenced by functional relations
      among those objects. In this study, observers indicated whether a target object
      matched a label. Each target was presented with a distractor object, and these
      were sometimes arranged to interact (as if being used together) and sometimes not
      to interact. When the distractor was semantically related to the label,
      identification was more accurate for targets arranged to interact with that
      distractor. This effect depended on observers' ability to perceptually integrate
      the stimulus objects, suggesting that it was perceptual in nature. The effect was
      not attributable to attentional cuing and did not depend on expectation of
      certain object pairs. These data suggest that familiar functional groupings of
      objects are perceptually grouped.

PMID- 17002526
TI  - Word length and lexical activation: longer is better.
AB  - Many models of spoken word recognition posit the existence of lexical and
      sublexical representations, with excitatory and inhibitory mechanisms used to
      affect the activation levels of such representations. Bottom-up evidence provides
      excitatory input, and inhibition from phonetically similar representations leads
      to lexical competition. In such a system, long words should produce stronger
      lexical activation than short words, for 2 reasons: Long words provide more
      bottom-up evidence than short words, and short words are subject to greater
      inhibition due to the existence of more similar words. Four experiments provide
      evidence for this view. In addition, reaction-time-based partitioning of the data
      shows that long words generate greater activation that is available both earlier
      and for a longer time than is the case for short words. As a result, lexical
      influences on phoneme identification are extremely robust for long words but are
      quite fragile and condition-dependent for short words. Models of word recognition
      must consider words of all lengths to capture the true dynamics of lexical
      activation.

PMID- 17002527
TI  - Distractor interference during smooth pursuit eye movements.
AB  - When 2 targets for pursuit eye movements move in different directions, the eye
      velocity follows the vector average (S. G. Lisberger & V. P. Ferrera, 1997). The
      present study investigates the mechanisms of target selection when observers are
      instructed to follow a predefined horizontal target and to ignore a moving
      distractor stimulus. Results show that at 140 ms after distractor onset,
      horizontal eye velocity is decreased by about 25%. Vertical eye velocity
      increases or decreases by 1 degrees /s in the direction opposite from the
      distractor. This deviation varies in size with distractor direction, velocity,
      and contrast. The effect was present during the initiation and steady-state
      tracking phase of pursuit but only when the observer had prior information about
      target motion. Neither vector averaging nor winner-take-all models could predict
      the response to a moving to-be-ignored distractor during steady-state tracking of
      a predefined target. The contributions of perceptual mislocalization and spatial
      attention to the vertical deviation in pursuit are discussed.

PMID- 17002528
TI  - The day of the week when you were born in 700 ms: calendar computation in an
      Autistic savant.
AB  - Some individuals are able to determine the weekday of a given date in a few
      seconds (finding for instance that June 12, 1900, was a Tuesday). This ability
      has fascinated scientists for many years because it is predominantly observed in
      people with limited intelligence and may appear very early in life. Exceptional
      visual memory, exceptional concentration abilities, or privileged access to lower
      levels of information not normally available through introspection have been
      advanced to explain such phenomena. In the present article, the authors show that
      a simple cognitive model can explain all aspects of the performance of Donny, a
      young autistic savant who is possibly the fastest and most accurate calendar
      prodigy ever described.

PMID- 17002529
TI  - Independent representation of parts and the relations between them: evidence from
      integrative agnosia.
AB  - Whether objects are represented as a collection of parts whose relations are
      coded independently remains a topic of ongoing discussion among theorists in the
      domain of shape perception. S. M., an individual with integrative agnosia, and
      neurologically intact ("normal") individuals learned initially to identify 4
      target objects constructed of 2 simple volumetric parts. At test, the targets
      were mixed with distractors, some of which could be discriminated from the
      targets on the basis of a mismatching part, whereas the rest could be
      discriminated only on the basis of the altered spatial arrangements of parts. S.
      M. learned to identify the target objects, although at a rate slower than that of
      the normal participants. At test, he correctly rejected distractors on the basis
      of mismatching parts but was profoundly impaired at rejecting distractors made of
      the same local components but with mismatching spatial arrangements. These
      results suggest that encoding the spatial arrangements of parts of an object
      requires a mechanism that is different from that required for encoding the shape
      of individual parts, with the former selectively compromised in integrative
      agnosia.

PMID- 17002530
TI  - Perception of initial moving target signals: support for a cumulative lateral
      inhibition theory.
AB  - The cumulative lateral inhibition (CLI) theory of the Frohlich effect (perceptual
      mislocalization of the starting position of a moving target in the direction of
      movement) proposes that the target is difficult to see early in its trajectory
      because inhibitory feedback from later target views weakens initial target
      representations. In contrast, attention shift explanations contend that a
      phenomenal representation of the target is unavailable until attention has
      shifted to the vicinity of the target. Experiments 1-3 demonstrated that
      instructing naive undergraduate participants to accept different degrees of
      target clarity before making their response can alter the magnitude (and
      presence) of the Frohlich effect. Experiments 2-4 showed that increasing movement
      distance by adding target presentations reduced the visibility of the target at
      early positions. These results are difficult to reconcile with an attention shift
      account.

PMID- 17002531
TI  - Shared spatial representations for numbers and space: the reversal of the SNARC
      and the Simon effects.
AB  - In 4 experiments, the authors investigated the reversal of spatial congruency
      effects when participants concurrently practiced incompatible mapping rules (J.
      G. Marble & R. W. Proctor, 2000). The authors observed an effect of an explicit
      spatially incompatible mapping rule on the way numerical information was
      associated with spatial responses. The authors also observed an effect of an
      incompatible numerical mapping rule (if smaller than 5, press right; if larger
      than 5, press left) on the Simon effect. This effect was observed only when both
      tasks used the same effectors. The results point to a shared spatial
      representation for explicit spatial information (locations) and implicit spatial
      information (numbers).

PMID- 17002532
TI  - Interrupted visual searches reveal volatile search memory.
AB  - This study investigated memory from interrupted visual searches. Participants
      conducted a change detection search task on polygons overlaid on scenes. Search
      was interrupted by various disruptions, including unfilled delay, passive viewing
      of other scenes, and additional search on new displays. Results showed that
      performance was unaffected by short intervals of unfilled delay or passive
      viewing, but it was impaired by additional search tasks. Across delays, memory
      for the spatial layout of the polygons was retained for future use, but memory
      for polygon shapes, background scene, and absolute polygon locations was not. The
      authors suggest that spatial memory aids interrupted visual searches, but the use
      of this memory is easily disrupted by additional searches.

PMID- 17002533
TI  - Are some gestalt principles deployed more readily than others during early
      development? The case of lightness versus form similarity.
AB  - Four experiments investigated how readily infants achieve perceptual organization
      by lightness and form similarity. Infants were (a) familiarized with elements
      that could be organized into rows or columns on the basis of lightness or form
      similarity and tested with vertical versus horizontal bars depicting the familiar
      versus novel organization or (b) familiarized with bars and tested with elements.
      For lightness similarity, generalization occurred in both tasks; however, for
      form similarity, generalization occurred only in the elements --> bars task. The
      findings indicate that lightness similarity is more readily deployed than form
      similarity and are discussed in the context of (a) whether the difference
      reflects speed of application or experience-based learning, (b) evidence from
      visual agnosic patients and the time course of application of the principles in
      healthy adults, and (c) development of dorsal and ventral visual processing
      streams.

PMID- 17002534
TI  - Inhibitory influences on asynchrony as a cue for auditory segregation.
AB  - A harmonic that begins before the other harmonics contributes less than they do
      to vowel quality. This reduction can be partly reversed by accompanying the
      leading portion with a captor tone. This effect is usually interpreted as
      reflecting perceptual grouping of the captor with the leading portion. Instead,
      it has recently been proposed that the captor effect depends on broadband
      inhibition within the central auditory system. A test of psychophysical
      predictions based on this proposal showed that captor efficacy is (a) maintained
      for noise-band captors, (b) absent when a captor accompanies a harmonic that
      continues after the vowel, and (c) maintained for 80 ms or more over a gap
      between captor offset and vowel onset. These findings support and refine the
      inhibitory account.

PMID- 17002535
TI  - Feature-based memory-driven attentional capture: visual working memory content
      affects visual attention.
AB  - In 7 experiments, the authors explored whether visual attention (the ability to
      select relevant visual information) and visual working memory (the ability to
      retain relevant visual information) share the same content representations. The
      presence of singleton distractors interfered more strongly with a visual search
      task when it was accompanied by an additional memory task. Singleton distractors
      interfered even more when they were identical or related to the object held in
      memory, but only when it was difficult to verbalize the memory content.
      Furthermore, this content-specific interaction occurred for features that were
      relevant to the memory task but not for irrelevant features of the same object or
      for once-remembered objects that could be forgotten. Finally, memory-related
      distractors attracted more eye movements but did not result in longer fixations.
      The results demonstrate memory-driven attentional capture on the basis of content
      specific representations.

PMID- 17002536
TI  - Haptic tracking permits bimanual independence.
AB  - This study shows that in a novel task-bimanual haptic tracking-neurologically
      normal human adults can move their 2 hands independently for extended periods of
      time with little or no training. Participants lightly touched buttons whose
      positions were moved either quasi-randomly in the horizontal plane by 1 or 2
      human drivers (Experiment 1), in circle and square patterns in the vertical plane
      by 2 human drivers (Experiment 2), or at different frequencies in the horizontal
      plane by 2 human drivers (Experiment 3). Bimanual contact was maintained equally
      well in all conditions even though in Experiment 1 the left- and right-hand
      motions were uncorrelated (in the 2-driver condition), in Experiment 2 the left-
      and right-hand motions were spatially incongruous when circles and squares were
      tracked at the same time, and in Experiment 3 the left- and right-hand motions
      maintained different frequency ratios. Because haptic tracking has revealed that
      humans can in fact move their 2 hands independently, it may have potential as a
      new behavioral tool for revealing other perceptual-motor capabilities.

PMID- 17002537
TI  - Does a regional accent perturb speech processing?
AB  - The processing costs involved in regional accent normalization were evaluated by
      measuring differences in lexical decision latencies for targets placed at the end
      of sentences with different French regional accents. Over a series of 6
      experiments, the authors examined the time course of comprehension disruption by
      manipulating the duration and presentation conditions of accented speech. Taken
      together, the findings of these experiments indicate that regional accent
      normalization involves a short-term adjustment mechanism that develops as a
      certain amount of accented signal is available, resulting in a temporary
      perturbation in speech processing.

PMID- 17002538
TI  - Target location probability effects in visual search: an effect of sequential
      dependencies.
AB  - Target location probability was manipulated in a visual search task. When the
      target was twice as likely to appear on 1 side of the display as the other,
      manual button-press response times were faster (Experiment 1A) and first saccades
      were more frequently directed (Experiment 1B) to the more probable locations.
      When the target appeared with equal probability at each location in this search
      task, performance benefited from repetition of target location in the preceding
      trials (Experiment 2). When the trial sequence was constrained so that target
      location did not repeat within a series of 4 trials, there was no longer an
      advantage for more probable locations (Experiment 3). The authors conclude that
      the search benefits for more probable locations resulted from short-term target
      location repetitions.

PMID- 17002540
TI  - Modeling pneumococcal resistance to penicillin in southern Sweden using
      artificial neural networks.
AB  - In recent decades, penicillin-resistant pneumococci (PRP) have emerged and spread
      rapidly between and within countries over the world. In this study we developed
      an iterative artificial neural network (ANN) model to describe and predict the
      spread of PRP in space and time as a function of antibiotic consumption and a
      number of different confounders. Retrospective data from 1997 to 2000 on an
      international epidemic PRP clone (serotype 9V) and antibiotic consumption data
      from Southern Sweden were used to train the ANN models and data from 2001 to 2003
      for evaluation of the model predictions. Five different ANN models were trained,
      each with independent topology optimization for alternative sets of input
      variables to find the most descriptive model. The model containing all variables
      was the only one performing better than the reference linear models, as assessed
      by the correlation between predictions and observations. The inability to
      identify a smaller subset of most predictive parameters may reflect either
      diffuse causal mechanisms or just the absence of critical experimental indicators
      from the dataset. The iterative ANN model identified is useful to predict future
      data. The sensitivity analysis of the model suggests that past incidence has a
      small effect on the number of PRP cases.

PMID- 17002541
TI  - Antibacterial use and Streptococcus pneumoniae penicillin resistance: A temporal
      relationship model.
AB  - The nature of the temporal relationship between antibacterial consumption and
      Streptococcus pneumoniae penicillin resistance is investigated using population
      level data across time. IMS Health Global Services provided national outpatient
      antibiotic prescription data for the years 1996-2003 from France, Spain, Italy,
      Germany, the United Kingdom, and the United States. Surveillance data consist of
      S. pneumoniae isolates obtained from a surveillance database in the same
      geographic regions from 1996 to 2003. A linear mixed model for repeated measures
      was used to analyze the association between resistance and several antibacterial
      classes through time. Changes in penicillin resistance through time in any
      country are better explained by the weighted cumulative antibacterial consumption
      with a 2-year lag. Narrow-spectrum penicillins are associated with lower
      resistance rates. Large reductions in consumption at the population level are
      needed to affect resistance. There is a peak level of penicillin resistance
      associated with cumulative exposure to a combination of antibiotic classes that
      is unique for every country.

PMID- 17002542
TI  - Augmentation of the antimicrobial efficacy of antibiotics by filamentous phage.
AB  - A significant increase in sensitivity to several antibiotics was observed in
      vitro after infection of the two Pseudomonas aeruginosa strains O1 and K with the
      filamentous phage Pf3 and Pf1, respectively. Moreover, upon infection with phage
      Pf1 a P. aeruginosa K strain harboring a plasmid-borne gentamicin resistance gene
      could be resensitized to the antibiotic. We further show that BALB/c mice were
      rescued from lethal infections with P. aeruginosa K by concomitant treatment with
      phage Pf1 and low concentrations of gentamicin, neither of which was able to cure
      the infection when administered alone.

PMID- 17002543
TI  - The role of antimicrobial use in the epidemiology of resistant pneumococci: A 10
      year follow up.
AB  - The relative effects of risk factors on the prevalence of resistant pneumococcal
      clones are hard to determine. Our aim was to evaluate the effect of risk factors
      on the prevalence of resistant pneumococci in Iceland in 2003 and compare these
      data with results of identical studies performed in 1993 and 1998. A randomized
      sample of 1,107 children was chosen from all 2,532 children 1 to 6 years old
      living in four communities. Pneumococci were carried by 64% of the 824 children
      enrolled and 9.5% were penicillin nonsusceptible (PNSP), as opposed to 8.1%
      (1998) and 8.5% (1993), and multiresistant strains of serotype 6B were 2.5%
      compared to 7.5% and 7.7% (p < 0.001). Antimicrobial use had declined in 10 years
      from 1.5 to 1.0 courses/child per year. The only significant risk factor for
      carriage of PNSP and erythromycin-resistant pneumococci was antimicrobial
      consumption. The multiresistant type 6B strains disappeared from the areas with
      the lowest antimicrobial use but maintained unchanged prevalence in the area with
      the highest use. The number of erythromycin- resistant, penicillin-susceptible
      strains of all pneumococci (37/475, 7.8%) increased significantly from the
      previous studies (7/353, 2.0%, 1998, and 2/390, 0.5%, 1993). This observation is
      associated with increased use of macrolides, especially azithromycin, in one of
      the study areas. Spread of novel resistant clones appears to be the main reason
      for rapid and significant changes in pneumococcal resistance rates. The choice of
      antimicrobial class appears to influence the selective environment favoring
      particular resistant clones.

PMID- 17002544
TI  - Detection of methicillin/oxacillin resistance and typing in aminoglycoside
      susceptible methicillin-resistant and kanamycin-tobramycin-resistant methicillin
      susceptible Staphylococcus aureus.
AB  - Eighty-five atypical isolates of Staphylococcus aureus divided into 73
      aminoglycoside-susceptible methicillinresistant (AS-MRSA) and 12 kanamycin
      tobramycin-resistant methicillin-susceptible (KTR-MSSA) were phenotypically and
      genotypically examined for methicillin resistance. Among these tests, the
      diffusion method using the oxacillin and cefoxitin disks on Mueller-Hinton agar
      with and without NaCl, the incubation at 35 degrees C or 30 degrees C for 24 or
      48 hr, respectively, and the determination of oxacillin MICs by E-test were
      performed. We also examined the presence of the mecA gene by PCR and its product
      PBP 2a by the Slidex MRSA Detection test after induction by cefoxitin disk. All
      of the AS-MRSA strains (100%) were detected by the cefoxitin disk in all
      conditions and by the oxacillin disk on Mueller-Hinton agar with 2% of NaCl at 35
      degrees C. Without NaCl, the sensitivity fell to 97.2% by oxacillin disk. The
      oxacillin MICs for these isolates ranged from 2 to 128 mg/L. The mecA gene
      determinant and its product PBP 2a were detected in all AS-MRSA strains. All KTR
      MSSA strains were phenotypically methicillin-susceptible and oxacillin MICs were
      below or borderline of breakpoint (< or =2 mg/L). The mecA gene determinant and
      its product were detected in one strain. Pulsed-field gel electrophoresis (PFGE)
      was applied and revealed the presence of two major patterns A (36.9%) and B
      (46.2%) in AS-MRSA isolates and seven patterns in the KTR-MSSA strains.

PMID- 17002545
TI  - Evaluation and genotyping of multidrug-resistant cases of tuberculosis in
      southern Brazil.
AB  - Sixty isolates of Mycobacterium tuberculosis identified as multidrug-resistant
      (MDR) at a reference laboratory in Rio Grande do Sul State during the years 1999
      and 2000 were analyzed using the IS6110-restriction fragment length polymorphism
      (RFLP) technique. We also genotyped 202 susceptible strains to compare the
      genotyping results, as well as the clinical and demographic data. Spacer
      oligotyping (spoligotyping) analysis was performed for isolates presenting low
      IS6110 copy number. Patients with identical DNA pattern strains were considered
      clustered. From 262 isolates, 94 (36%) belonged to 20 distinct RFLP clusters, and
      after spoligotyping analysis, 89 of the isolates (34%) remained in cluster. MDR
      isolates did not differ statistically in clustering proportion from susceptible
      strains. A significant association between the occurrence of MDR and previous
      tuberculosis (TB) treatment was observed (p < 0.001), as well as failure on TB
      treatment (p < 0.001). Human immunodeficiency virus (HIV)-positive patients were
      associated with susceptible tuberculosis (p = 0.024). We also identified that
      unmarried patients were more likely to develop TB due to recent transmission than
      married patients (p < 0.005). The introduction of directly observed therapy short
      course (DOTS) strategy will be important in decreasing default and failure rates
      and avoiding the development of new MDR strains.

PMID- 17002546
TI  - Molecular characterization and occurrence of extended-spectrum beta-lactamase
      resistance genes among Salmonella enterica serovar Corvallis from Thailand,
      Bulgaria, and Denmark.
AB  - Fifty nine Salmonella Corvallis isolates from humans and food products in
      Bulgaria, Denmark, and Thailand were examined for antimicrobial susceptibility
      and characterized by pulsed-field gel electrophoresis (PFGE). Cephalosporin
      resistant isolates were examined for the presence of genes encoding beta
      lactamases by PCR and sequencing. Ten different PFGE types were observed. One
      type (30 isolates) was recovered in all three countries; three types were found
      only in Bulgaria, two only in Denmark, two only in Thailand, and two both in
      Denmark and Thailand. Ten isolates were susceptible to all antimicrobial agents
      tested, whereas 41 were resistant to three or more antimicrobials. Most
      resistance was observed among the isolates from Bulgaria. Of the 25 isolates from
      Bulgaria, 20 displayed resistance to ampicillin and the cephalosporins ceftiofur
      and cephalothin. All 20 isolates tested negative for bla (CMY-1), bla (CMY-2),
      and bla (ACC), but positive for bla (SHV), of which five were sequenced to bla
      (SHV-2). Plasmid profiling and hybridization revealed that the bla (SHV) gene was
      located on plasmids of approximately 70 kb. Five plasmid profiles were found
      among these 20 isolates. The plasmid profiling confirmed the PFGE-type and was
      able to further subdivide the strains. Seventeen of these 20 isolates contained
      also bla (TEM), of which nine representatives were sequenced to bla (TEM-1B), or
      bla (TEM-1H). One isolate contained bla (CTX-M-15), bla (SHV-2), and bla (TEM
      1H), with the bla (CTX-M-15), and bla (TEM-1H) genes located on a 63-kb
      transferable plasmid. This study showed a high frequency of resistance among S.
      Corvallis isolated from humans and food products in Bulgaria, with a lower
      frequency in Thailand and Denmark. The clonal relatedness among the isolates from
      three countries could indicate a recent spread of this serovar.

PMID- 17002547
TI  - Penicillin susceptibility of non-serotypeable Streptococcus pneumoniae from
      ophthalmic specimens.
AB  - Nontypeable (NT) Streptococcus pneumoniae strains isolated from eyes were
      examined for both penicillin susceptibility by E-test and penicillin-binding
      protein (PBP) gene alterations using PCR. Of the 25 ophthalmic isolates, 15
      proved to be sensitive (PSSP, MIC < or = 0.06 microg/ml) and 10 were shown as
      intermediately resistant to penicillin (PISP, MIC = 0.1-1 microg/ml). No
      penicillin-resistant S. pneumoniae (PRSP, MIC > or = 2 microg/ml) were found. PBP
      gene (pbp1a and pbp2b) alteration PCR indicated that 12 (80.0%) of the 15
      ophthalmic PSSPs had unaltered pbp genes and that 3 (20.0%) had alterations in
      either pbp1a or pbp2b, whereas 8 (80.0%) of the 10 PISPs had unaltered pbp genes
      and 2 (20.0%) had alterations in both pbp1a and pbp2b. These data suggest that
      penicillin resistance is spread among NT pneumococci typically associated with
      ophthalmic infections.

PMID- 17002548
TI  - Dissemination of extended-spectrum beta-lactamase-producing Enterobacteriaceae in
      intensive care units of a medical center in Taiwan.
AB  - The prevalence of extended-spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae in a tertiary hospital in Taiwan was assessed over a 16-month
      period. A total of 125 nonrepetitive ESBL-producing isolates of Enterobacter
      cloacae, Escherichia coli, and Klebsiella pneumoniae were available for
      investigation using molecular methods. Four predominant intensive care units
      (ICUs) were identified, and SHV-12 (59%), CTX-M- 3 (36%), and CTX-M-14 (14%) were
      the three most frequent ESBLs. SHV-12 was predominant among E. cloacae in the
      burn unit and K. pneumoniae in the other three chest medicine-related ICUs. CTX-M
      3 was predominant among E. coli and K. pneumoniae in three other ICUs. The
      dissemination of ESBL-producing Enterobacteriaceae in four ICUs of a medical
      center in Taiwan is a consequence of the clonal dissemination of a few epidemic
      strains along with the horizontal transmission of resistance genes-carrying
      plasmids among bacterial organisms.

PMID- 17002549
TI  - The effect of subtherapeutic chlortetracycline on antimicrobial resistance in the
      fecal flora of swine.
AB  - The aims of this research were to determine the association between inclusion of
      subtherapeutic chlortetracycline in the diets of swine and the prevalence and
      antimicrobial resistance of Salmonella; define the association between inclusion
      of subtherapeutic chlortetracycline and antimicrobial resistance in the aerobic
      Gram-negative fecal flora of swine; and estimate the proportion of total model
      variance attributable to farm, pig, and colony level effects. There was no
      association between subtherapeutic chlortetracycline exposure and Salmonella
      prevalence. There were increased odds for an aerobic Gram-negative fecal isolate
      to be resistant to ampicillin, ceftriaxone, and tetracycline if isolated from a
      pig that received chlortetracycline. There was a positive association between
      inclusion of subtherapeutic chlortetracycline in the diet and resistance to
      multiple antimicrobials. The proportion of total variance associated with farm,
      pig, and colony varied based on the resistance phenotype. Because farm-level
      variance contributed a small proportion to total variance in all models, effects
      of antimicrobial use interventions observed in this study may be predictive of
      anticipated impact of interventions on most swine farms. Resources for future
      investigations may be better allocated to sampling more pigs and more bacterial
      colonies per pig in relationship to the number of farms.

PMID- 17002550
TI  - Quality-control ranges for antimicrobial susceptibility testing by broth dilution
      of the Brachyspira hyodysenteriae type strain (ATCC 27164T).
AB  - There are no approved standards for antimicrobial susceptibility testing of the
      fastidious spirochete Brachyspira hyodysenteriae. An interlaboratory study was
      performed to establish MIC quality control ranges for six antimicrobial agents
      for the type strain of B. hyodysenteriae using broth dilution. The results showed
      that B. hyodysenteriae B78T ATCC 27164T is a suitable quality control strain.
      This is a first step toward standardization of methods regarding this anaerobe.

PMID- 17002551
TI  - Why hasn't eliminating acute rejection improved graft survival?
AB  - Although patients with end-stage renal disease can be maintained with dialysis
      therapy, the superiority of patient survival with renal transplantation makes
      transplantation the preferred method of renal replacement. Potent
      immunosuppressive therapies, particularly calcineurin inhibitors, have greatly
      reduced the incidence of acute rejection. However, long-term allograft survival
      remains limited. We discuss the impact of acute rejection on long-term allograft
      survival and discuss other factors leading to late allograft loss, including
      calcineurin inhibitor toxicity, chronic allograft nephropathy, and BK virus
      nephropathy, as well as donor and recipient factors associated with long-term
      allograft loss.

PMID- 17002552
TI  - Cancer stem cells: models and concepts.
AB  - Although monoclonal in origin, most tumors appear to contain a heterogeneous
      population of cancer cells. This observation is traditionally explained by
      postulating variations in tumor microenvironment and coexistence of multiple
      genetic subclones, created by progressive and divergent accumulation of
      independent somatic mutations. An additional explanation, however, envisages
      human tumors not as mere monoclonal expansions of transformed cells, but rather
      as complex tridimensional tissues where cancer cells become functionally
      heterogeneous as a result of differentiation. According to this second scenario,
      tumors act as caricatures of their corresponding normal tissues and are sustained
      in their growth by a pathological counterpart of normal adult stem cells, cancer
      stem cells. This model, first developed in human myeloid leukemias, is today
      being extended to solid tumors, such as breast and brain cancer. We review the
      biological basis and the therapeutic implications of the stem cell model of
      cancer.

PMID- 17002553
TI  - Social cognitive neuroscience: a review of core processes.
AB  - Social cognitive neuroscience examines social phenomena and processes using
      cognitive neuroscience research tools such as neuroimaging and neuropsychology.
      This review examines four broad areas of research within social cognitive
      neuroscience: (a) understanding others, (b) understanding oneself, (c)
      controlling oneself, and (d) the processes that occur at the interface of self
      and others. In addition, this review highlights two core-processing distinctions
      that can be neurocognitively identified across all of these domains. The
      distinction between automatic versus controlled processes has long been important
      to social psychological theory and can be dissociated in the neural regions
      contributing to social cognition. Alternatively, the differentiation between
      internally-focused processes that focus on one's own or another's mental interior
      and externally-focused processes that focus on one's own or another's visible
      features and actions is a new distinction. This latter distinction emerges from
      social cognitive neuroscience investigations rather than from existing
      psychological theories demonstrating that social cognitive neuroscience can both
      draw on and contribute to social psychological theory.

PMID- 17002555
TI  - RANKL treatment releases the negative regulation of the poly(ADP-ribose)
      polymerase-1 on Tcirg1 gene expression during osteoclastogenesis.
AB  - The Tcirg1 gene encodes the osteoclast-specific a3 isoform of the V-ATPase a
      subunit. Using the mouse osteoclastic model RAW264.7 cells, we studied Tcirg1
      gene expression, and we identified PARP-1 as a transcriptional repressor
      negatively regulated by RANKL during osteoclastogenesis. INTRODUCTION: The TCIRG1
      gene encodes the a3 isoform of the V-ATPase a subunit, and mutations at this
      locus account for approximately 60% of infantile malignant osteopetrosis cases.
      Using RAW264.7 cells as an osteoclastic differentiation model, we undertook a
      transcriptional study of the mouse Tcirg1 gene focused on the 4-kb region
      upstream of the transcription starting point. MATERIALS AND METHODS: The promoter
      activity of serial-deletion fragments of the Tcirg1 gene promoter was monitored
      throughout the RAW264.7 cell differentiation process. We next performed EMSA, UV
      cross-linking, affinity purification, mass spectrometry analysis, gel supershift,
      and siRNA transfection experiments to identify the factor(s) interacting with the
      promoter. RESULTS: The -3946/+113 region of the mouse Tcirg1 gene displayed a
      high basal promoter activity, which was enhanced by RANKL treatment of RAW264.7
      cells. Constructs deleted up to -1589 retained this response to RANKL. A deletion
      up to -1402 induced a 3-fold enhancement of the basal activity, whereas RANKL
      response was not affected. EMSA experiments led us to identify within the -1589/
      1402 region, a 10-nucleotide sequence, which bound a nuclear protein present in
      nondifferentiated RAW264.7 cells. This interaction was lost using nuclear
      extracts derived from RANKL-treated cells. Affinity purification followed by mass
      spectrometry analysis and gel supershift assay allowed the identification of
      poly(ADP-ribose) polymerase-1 (PARP-1) as this transcriptional repressor, whereas
      Western blot experiments revealed the cleavage of the DNA-binding domain of PARP
      1 on RANKL treatment. Finally, both PARP-1 depletion after siRNA transfection and
      RAW264.7 cell treatment by an inhibitor of PARP-1 activity induced an increase of
      a3 mRNA expression. CONCLUSIONS: We provide evidence that the basal transcription
      activity of the Tcirg1 gene is negatively regulated by the binding of PARP-1
      protein to its promoter region in mouse pre-osteoclast. On RANKL treatment, PARP
      1 protein is cleaved and loses its repression effect, allowing an increase of
      Tcirg1 gene expression that is critical for osteoclast function.

PMID- 17002556
TI  - Transmigration: a new property of mature multinucleated osteoclasts.
AB  - Even though it is assumed that multinucleated osteoclasts are migrating cells on
      the bone surface to be resorbed, we show that they can also selectively
      transmigrate through layers of cells usually found in the bone microenvironment.
      This activity is associated with c-src and MMPs and can be stimulated by bone
      metastatic breast cancer cells, a process blocked by bisphosphonate treatment.
      INTRODUCTION: Osteoclasts have an hematopoietic origin and are bone-resorbing
      cells. Monocytic precursors migrate to the bone surface where they fuse to form
      multinucleated osteoclasts able to migrate over the bone surface. We studied
      whether multinucleated osteoclasts were also able to transmigrate through
      tissues. MATERIALS AND METHODS: Murine spleen-derived and green fluorescent
      protein (GFP)-Raw derived osteoclasts were seeded on osteoblasts and several
      other cell types. The cells were fixed for 20 minutes, 4 or 12 h after osteoclast
      seeding, and stained with phalloidin to visualize actin using confocal
      microscopy. Drugs such as PP2 and GM6001, inhibitors of c-src and matrix
      metalloproteinases (MMPs), respectively, and risedronate were used to determine
      osteoclast transmigration regulating factors. RESULTS: We observed by confocal
      microscopy that multinucleated osteoclasts specifically transmigrate through
      confluent layers of various cell types present in the bone microenvironment in
      vitro. This is an efficient process associated with c-src and MMPs but is
      independent of podosomes. Moreover, conditioned medium from bone metastatic
      breast cancer cells stimulates osteoclast transmigration in vitro, a process
      inhibited by bisphosphonate treatment. CONCLUSIONS: Our data describe a new
      property of mature multinucleated osteoclasts to transmigrate through various
      cell types. The ability to control this highly regulated osteoclast
      transmigration process may offer new therapeutic strategies for bone diseases
      associated with an imbalance in bone remodeling caused by excessive osteoclast
      resorption.

PMID- 17002554
TI  - The experience of emotion.
AB  - Experiences of emotion are content-rich events that emerge at the level of
      psychological description, but must be causally constituted by neurobiological
      processes. This chapter outlines an emerging scientific agenda for understanding
      what these experiences feel like and how they arise. We review the available
      answers to what is felt (i.e., the content that makes up an experience of
      emotion) and how neurobiological processes instantiate these properties of
      experience. These answers are then integrated into a broad framework that
      describes, in psychological terms, how the experience of emotion emerges from
      more basic processes. We then discuss the role of such experiences in the economy
      of the mind and behavior.

PMID- 17002557
TI  - Leptin is a negative independent predictor of areal BMD and cortical bone size in
      young adult Swedish men.
AB  - The association between leptin and areal BMD has been controversial, and the
      predictive role of leptin on cortical volumetric BMD and bone size has not
      previously been studied. We show that leptin is a negative independent predictor
      of aBMD (DXA), at several measured sites, and of cortical bone size (pQCT) in a
      large population of young men. INTRODUCTION: Recent findings suggest that both
      adipose tissue (AT) and bone mass are regulated by leptin. Previous reports
      studying the association between leptin and areal BMD (aBMD) have yielded
      conflicting results. The role of leptin on volumetric BMD (vBMD) and bone size of
      the cortical and trabecular bone compartments has not previously been studied.
      MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants
      (GOOD) study is a population-based study of 1068 men (age, 18.9 +/- 0.6 [SD]
      years). aBMD of the total body, lumbar spine, femoral neck, both radii, and
      trochanter, as well as total body AT and lean mass (LM) were measured using DXA,
      whereas cortical and trabecular vBMD and bone size were measured by pQCT.
      RESULTS: Total body LM could explain a larger magnitude of the difference in the
      variation in aBMD and cortical bone size than what total body AT could (total
      body aBMD: LM 37.4% versus AT 8.7%; tibia cross-sectional area [CSA]: LM 46.8%
      versus AT 5.6%). The independent role of leptin on bone parameters was studied
      using a multiple linear regression model, including age, total body LM and AT,
      height, present physical activity, calcium intake, and smoking as covariates.
      Leptin was found to be a negative independent predictor of aBMD (total body: beta
      = -0.08, p = 0.01; lumbar spine: beta = -0.13, p < 0.01; trochanter: beta = 
      0.09, p = 0.01), as well as of the cortical bone size (CSA and thickness) of both
      the radius (CSA: beta = -0.12, p < 0.001) and tibia (CSA: beta = -0.08, p <
      0.01), but not of the cortical or trabecular vBMD of these bones. CONCLUSION: Our
      results indicate that LM has a greater impact on bone mass than AT. Our findings
      further show that leptin is a negative independent predictor of aBMD at several
      measured sites and of bone parameters reflecting cortical bone size, but not
      vBMD, in a large population of young Swedish men.

PMID- 17002558
TI  - On the increasing fragility of human teeth with age: a deep-UV resonance Raman
      study.
AB  - UV resonance Raman spectroscopy (UVRRS) using 244-nm excitation was used to study
      the impact of aging on human dentin. The intensity of a spectroscopic feature
      from the peptide bonds in the collagen increases with tissue age, similar to a
      finding reported previously for human cortical bone. INTRODUCTION: The structural
      changes that lead to compromised mechanical properties with age in dentin and
      bone are under intense study. However, in situ analyses of the content and
      distribution of the mineral phase are more highly developed at present than
      equivalent probes of the organic phase. MATERIALS AND METHODS: Thirty-five human
      molars were divided into three groups: young/normal (23.3 +/- 3.8 years);
      aged/transparent (74.3 +/- 6.0 years), which had become transparent because of
      filling of the tubule lumens with mineral deposits; and aged/nontransparent (73.3
      +/- 5.7 years). Control experiments were performed by demineralizing normal
      dentin. RESULTS: Spectral features caused by both the amide backbone and
      resonance-enhanced side-chain vibrations were observed. This finding contrasts
      with reported Raman spectra of proteins in solution excited with similar UV
      wavelengths, where side chain vibrations, but not strong amide features, are
      observed. The strong intensity of the amide features observed from dentin is
      attributed to broadening of the resonance profile for the amide pi --> pi*
      transition caused by the environment of the collagen molecules in dentin. With
      increasing age, the height of one specific amide vibration (amide I) becomes
      significantly higher when comparing teeth from donors with an average age of 23
      years to those of 73 years (p < 0.001). This trend of increasing amide I peak
      height with age is similar to that previously reported for human cortical bone.
      The amide I feature also increased in dentin that had been demineralized and
      dehydrated. CONCLUSIONS: The similar trend of increasing amide I peak height with
      age in the UVRR spectra of both teeth and bone is surprising, given that only
      bone undergoes remodeling. However, by considering those observations together
      with this study of demineralized/dehydrated dentin and our prior work on dentin
      dehydrated with polar solvents, a consistent relationship between changes in the
      UVRR spectra and the collagen environment in the tissue can be developed.

PMID- 17002559
TI  - Advanced molecular profiling in vivo detects novel function of dickkopf-3 in the
      regulation of bone formation.
AB  - A bioinformatics-based analysis of endochondral bone formation model detected
      several genes upregulated in this process. Among these genes the dickkopf homolog
      3 (Dkk3) was upregulated and further studies showed that its expression affects
      in vitro and in vivo osteogenesis. This study indicates a possible role of Dkk3
      in regulating bone formation. INTRODUCTION: Endochondral bone formation is a
      complex biological process involving numerous chondrogenic, osteogenic, and
      angiogenic proteins, only some of which have been well studied. Additional key
      genes may have important roles as well. We hypothesized that to identify key
      genes and signaling pathways crucial for bone formation, a comprehensive gene
      discovery strategy should be applied to an established in vivo model of
      osteogenesis. MATERIALS AND METHODS: We used in vivo implanted C3H10T1/2 cells
      that had been genetically engineered to express human bone morphogenetic protein
      2 (BMP2) in a tetracycline-regulated system that controls osteogenic
      differentiation. Oligonucleotide microarray data from the implants (n = 4
      repeats) was analyzed using coupled two-way clustering (CTWC) and statistical
      methods. For studying the effects of dickkopf homolog 3 (Dkk3) in chondrogenesis
      and osteogenesis, C3H10T1/2 mesenchymal progenitors were used. RESULTS: The CTWC
      revealed temporal expression of Dkk3 with other chondrogenesis-, osteogenesis-,
      and Wnt-related genes. Quantitative RT-PCR confirmed the expression of Dkk3 in
      the implants. C3H10T1/2 cells that expressed Dkk3 in the presence of BMP2
      displayed lower levels of alkaline phosphatase and collagen I mRNA expression
      than control C3H10T1/2 cells that did not express Dkk3. Interestingly, the levels
      of collagen II mRNA expression, Alcian blue staining, and glucose aminoglycans
      (GAGs) production were not influenced by Dkk3 expression. In vivo microCT and
      bioluminescence imaging revealed that co-expression of Dkk3 and BMP2 by implanted
      C3H10T1/2 cells induced the formation of significantly lower quantities of bone
      than cells expressing only BMP2. CONCLUSIONS: A bioinformatics analysis enabled
      the identification of Dkk3 as a pivotal gene with a novel function in
      endochondral bone formation. Our results showed that Dkk3 might have inhibitory
      effects on osteogenesis, but no effect on chondrogenesis, indicating that Dkk3
      plays a regulatory role in endochondral bone formation. Further mechanistic
      studies are required to reveal the mechanism of action of Dkk3 in endochondral
      bone formation.

PMID- 17002560
TI  - T lymphocyte-deficient mice lose trabecular bone mass with ovariectomy.
AB  - We examined OVX-induced bone loss in three TLD mouse models. In TLD mice, OVX
      caused trabecular bone loss equivalent to that of WT. In contrast, cortical bone
      loss with OVX was variable. We conclude that T lymphocytes do not influence OVX
      induced trabecular bone loss. INTRODUCTION: We examined ovariectomy (OVX)-induced
      bone loss in three T lymphocyte-deficient (TLD) mouse models: nude mice,
      recombination activating gene 2-deficient (RAG2 KO) mice, and T cell receptor
      alpha chain-deficient (TCRalpha KO) mice. MATERIALS AND METHODS: Bone mass was
      examined by DXA, microCT, and histomorphometry. We also examined the effect of
      OVX on T lymphocytes in the bone marrow and spleens of wildtype (WT) mice and on
      in vitro osteoclastogenesis and colony forming unit-granulocyte macrophage (CFU
      GM) activity in the bone marrow of WT and nude mice. RESULTS: In WT mice, OVX did
      not alter T lymphocyte number in the bone marrow but did increase T lymphocytes
      in the spleen. Comparison of bone mass in nude, RAG2 KO, and TCRalpha KO mice
      with WT as measured by DXA showed decreased femoral bone mass in nude mice and
      increased vertebral bone mass in RAG2 KO mice. In TCRalpha KO mice, femoral,
      tibial, and vertebral bone mass were decreased. In vertebrae and long bones, bone
      loss with OVX was consistently present in WT mice but variably present in TLD
      mice as measured by DXA. In contrast, microCT and histomorphometry showed similar
      trabecular bone loss after OVX in all mice. However, femoral cortical bone loss
      occurred only in WT and RAG2 KO mice. OVX produced similar trabecular bone loss
      in WT and TCRalpha KO mice and also induced cortical bone loss in both.
      Histomorphometry showed that TRACP(+) area in bones was increased by OVX in
      femurs from both WT and nude mice as was in vitro osteoclast-like cell formation
      and CFU-GM activity. CONCLUSIONS: These results show that OVX caused similar
      trabecular bone loss in both WT and TLD mice. The ability of DXA and measurement
      of cortical bone loss to show OVX-induced effects on bone mass was variable. It
      seems that T lymphocytes are not critical for OVX-induced trabecular bone loss in
      these mouse models.

PMID- 17002562
TI  - Cell-cell adhesion and signaling through cadherins: connecting bone cells in
      their microenvironment.

PMID- 17002563
TI  - Evidence for increased clinical severity of familial and sporadic Paget's disease
      of bone in Campania, southern Italy.
AB  - The analysis of 236 Italian patients with Paget's bone disease showed higher
      clinical severity and greater frequency of neoplastic degeneration among patients
      who live or descend from individuals living in the Campania region (southern
      Italy). A prevalent involvement of the spine and the skull, the sites
      preferentially involved in giant cell tumors complicating Paget's disease, was
      also shown in familial cases from this geographical region. INTRODUCTION: The
      Campania region in southern Italy has been recently indicated as a high
      prevalence area for Paget's disease of bone (PDB), and most pagetic families with
      multiple occurrence of neoplasms in affected members were from this geographical
      region. MATERIALS AND METHODS: We evaluated the PDB epidemiological
      characteristics in 125 patients from Campania in comparison with 111 patients
      from other Italian regions. Twenty-three patients from Campania and 26 patients
      from other Italian areas had at least one first-degree relative affected by PDB
      (familial cases). The remaining patients made up the sporadic cases. RESULTS:
      Among subjects from Campania, the patients in the familial group tended to come
      from larger families and showed at diagnosis higher serum total alkaline
      phosphatase, larger extension of disease, and earlier mean age with respect to
      patients with PDB of the sporadic group. The skull, spine, and humerus were the
      sites preferentially involved in the familial cases. In contrast, no such
      differences were observed between familial and sporadic PDB cases among patients
      from the other geographical areas, except for a lower age at diagnosis. An
      increased PDB clinical severity was finally observed in the PDB cohort from
      Campania in comparison with patients from other Italian regions. Neoplastic
      degeneration of pagetic bones (osteosarcoma and giant cell tumor) was exclusively
      observed in patients with polyostotic PDB from Campania. CONCLUSIONS: We showed a
      higher clinical severity of PDB with occurrence of neoplastic degeneration in the
      high prevalence area of Campania, with its maximum expression in cases with
      familial disease. This peculiar pattern might be traced to genetic predisposition
      and/or to the abnormal impact of a still undefined environmental trigger.

PMID- 17002564
TI  - Robust and comprehensive analysis of 20 osteoporosis candidate genes by very high
      density single-nucleotide polymorphism screen among 405 white nuclear families
      identified significant association and gene-gene interaction.
AB  - Many "novel" osteoporosis candidate genes have been proposed in recent years. To
      advance our knowledge of their roles in osteoporosis, we screened 20 such genes
      using a set of high-density SNPs in a large family-based study. Our efforts led
      to the prioritization of those osteoporosis genes and the detection of gene-gene
      interactions. INTRODUCTION: We performed large-scale family-based association
      analyses of 20 novel osteoporosis candidate genes using 277 single nucleotide
      polymorphisms (SNPs) for the quantitative trait BMD variation and the qualitative
      trait osteoporosis (OP) at three clinically important skeletal sites: spine, hip,
      and ultradistal radius (UD). MATERIALS AND METHODS: One thousand eight hundred
      seventy-three subjects from 405 white nuclear families were genotyped and
      analyzed with an average density of one SNP per 4 kb across the 20 genes. We
      conducted association analyses by SNP- and haplotype-based family-based
      association test (FBAT) and performed gene-gene interaction analyses using
      multianalytic approaches such as multifactor-dimensionality reduction (MDR) and
      conditional logistic regression. RESULTS AND CONCLUSIONS: We detected four genes
      (DBP, LRP5, CYP17, and RANK) that showed highly suggestive associations (10,000
      permutation derived empirical global p < or = 0.01) with spine BMD/OP; four genes
      (CYP19, RANK, RANKL, and CYP17) highly suggestive for hip BMD/OP; and four genes
      (CYP19, BMP2, RANK, and TNFR2) highly suggestive for UD BMD/OP. The associations
      between BMP2 with UD BMD and those between RANK with OP at the spine, hip, and UD
      also met the experiment-wide stringent criterion (empirical global p < or =
      0.0007). Sex-stratified analyses further showed that some of the significant
      associations in the total sample were driven by either male or female subjects.
      In addition, we identified and validated a two-locus gene-gene interaction model
      involving GCR and ESR2, for which prior biological evidence exists. Our results
      suggested the prioritization of osteoporosis candidate genes from among the many
      proposed in recent years and revealed the significant gene-gene interaction
      effects influencing osteoporosis risk.

PMID- 17002565
TI  - On genetic studies of bone loss.

PMID- 17002566
TI  - Does reduced skeletal loading account for age-related bone loss?
AB  - A leading theory suggests that decreasing activity and muscle mass is the main
      cause of age-related bone loss. However, in a population-based study of 375 women
      and 325 men (age, 21-97 years), we failed to find a close correspondence between
      these variables and changes in bone strength with aging. INTRODUCTION: It has
      been suggested that bone strength is homeostatically adapted to habitual skeletal
      loading conditions and that bone loss could, therefore, result simply from age
      related reductions in physical activity and muscle mass, but this notion has not
      been explored in detail. MATERIALS AND METHODS: In a stratified random sample of
      Rochester, MN, women and men 21-97 years of age, indices of bone strength,
      flexural rigidity (EI), and axial rigidity (EA) were estimated from central QCT
      measurements at the femoral neck and lumbar spine and pQCT measurements at the
      ultradistal radius, whereas habitual skeletal loading was assessed using lean
      body mass, total skeletal muscle mass (TSM), body weight, and physical activity.
      Using regression analysis, we tested the hypothesis (H(o)) that bone strength per
      unit load did not vary with age. RESULTS AND CONCLUSIONS: In these cross
      sectional data, the null hypothesis of no age-related change was rejected in 72%
      of the strength-to-load ratios tested. For example, the ratio of femoral neck EI
      to TSM increased by 0.19%/year in women (p = 0.008) and by 0.49%/year in men (p <
      0.001). There was no close correspondence between changes in habitual load and
      changes in bone strength, nor any consistent pattern. Moreover, interindividual
      variation in the strength-to-load ratios was substantial. These data suggest that
      the notion of reduced skeletal loading as the primary basis for age-related bone
      loss is oversimplified.

PMID- 17002567
TI  - Volumetric BMD and vascular calcification in middle-aged women: the Study of
      Women's Health Across the Nation.
AB  - The association of spine vBMD with AC and CAC was studied in a biracial cohort of
      490 middle-aged women in the Study of Women's Health Across the Nation. Lower
      vBMD was related to high AC, but not to CAC, independent of age and shared risk
      factors between osteoporosis and cardiovascular disease. INTRODUCTION: This
      analysis studied the association of spine volumetric BMD (vBMD) with aortic (AC)
      and coronary artery (CAC) calcification in middle-aged women and evaluated
      whether such associations were independent of age and shared risk factors between
      osteoporosis and cardiovascular disease (CVD) or explained by endogenous
      estradiol levels. MATERIALS AND METHODS: Vascular calcification and trabecular
      vBMD of the spine were measured using electron-beam CT in 490 women free from
      clinical CVD in the Study of Women's Health Across the Nation. Women were 45-58
      years of age, 61% were white, and 64% were perimenopausal. Calcification scores
      were categorized into three levels (no AC, N = 146; moderate AC, scores = 1-74, N
      = 221; high AC, N = 123; no CAC, N = 256; moderate CAC, score = 1-7.54, N = 111;
      high CAC, N = 123). The highest categories were set at the 75th percentiles.
      Multinomial logistic regression was used to assess the association between vBMD
      (per SD) and the AC and CAC levels, with no calcification as the reference group.
      RESULTS: AC and CAC were detected in 70% and 48% of the population, respectively.
      Mean vBMD was 161.6 +/- 37.2 (SD) mg/ml. vBMD was associated with high AC in
      unadjusted, age-adjusted, and risk factor-adjusted analysis. Per 1 SD decrease in
      vBMD, the adjusted odds of high AC compared with no AC was significantly
      increased by 68% (95% CI, 1.06-2.68). Estradiol did not influence this
      association. vBMD was related to high CAC in unadjusted (OR = 1.35; 95% CI, 1.08
      1.70) but not adjusted models. No associations of vBMD with moderate AC or CAC
      were observed. CONCLUSION: Lower vBMD was related to high AC, but not to CAC, in
      a biracial cohort of healthy middle-aged women independent of age and shared risk
      factors between osteoporosis and CVD. Further research should study possible
      pathophysiological links between the two conditions and the potential for common
      preventive and therapeutic interventions.

PMID- 17002568
TI  - Monostotic fibrous dysplasia of the proximal femur and liposclerosing myxofibrous
      tumor: which one is which?
AB  - Clinical, histological, and genetic studies of two cases of isolated fibro
      osseous lesions of the femur in adults show the overlap between monostotic
      fibrous dysplasia (MFD) of the proximal femur and the so-called liposclerosing
      myxofibrous tumor. The two cases highlight how the incomplete understanding of
      the natural history of MFD may result in diagnostic pitfalls or incorrect
      classification of individual lesions.

PMID- 17002569
TI  - Reduced peripheral nerve function is related to lower hip BMD and calcaneal QUS
      in older white and black adults: the Health, Aging, and Body Composition Study.
AB  - Bone tissue is innervated, and peripheral nerve function may impact BMD. Older
      black and white men and women (N = 2200) in the Health, Aging, and Body
      Composition Study with worse sensory and motor peripheral nerve function had
      lower hip BMD and calcaneal BUA independent of lean mass, strength, physical
      ability, and diabetes. Poor peripheral nerve function may directly affect bone.
      INTRODUCTION: Bone tissue is innervated, yet little is known about the impact of
      nerve function on BMD. Poor peripheral nerve function may contribute to lower BMD
      and higher fracture risk, particularly in those with diabetic neuropathy.
      MATERIALS AND METHODS: The Health, Aging, and Body Composition (Health ABC) Study
      included annual exams in white and black men and women 70-79 years of age
      recruited from Pittsburgh and Memphis. Nerve function in legs/feet was assessed
      by 1.4- and 10-g monofilament detection, vibration threshold, and peroneal motor
      nerve conduction velocity (NCV) and amplitude (CMAP). Total hip BMD, heel
      broadband ultrasound attenuation (BUA), and total fat and lean mass were measured
      1 year later (QDR 4500A, Sahara QUS; Hologic). RESULTS: Participants (N = 2200)
      were 48% men and 37% black. Poor nerve function (lower monofilament detection,
      higher vibration threshold, lower CMAP, lower NCV) was associated with 1.4-5.7%
      lower BUA and significant for all but NCV, adjusted for demographics, diabetes,
      body composition, and physical ability. Results were similar for adjusted hip
      BMD, with 1.0-2.9% lower BMD, significant for monofilament and CMAP testing. When
      considering the components of BMD, total hip area was 1.8-4.9% higher in those
      with the worst nerve function, although BMC showed little difference. Lower
      monofilament detection and CMAP were independently associated with lower heel BUA
      (p < 0.01), and monofilament detection was associated with lower hip BMD (p <
      0.05) in regression additionally adjusted for lifestyle factors, bone-active
      medications, and diabetes-related complications. CONCLUSIONS: Poor peripheral
      nerve function may directly related to lower BMD, likely through an increase in
      bone area in older adults, independent of lean mass, strength, physical ability,
      and diabetes. Whether those with impaired nerve function are at higher risk for
      fracture independent of falls needs to be studied.

PMID- 17002570
TI  - Bio imaging of intracellular NO production in single bone cells after mechanical
      stimulation.
AB  - We show the intracellular upregulation of NO production after mechanical
      stimulation, an essential chemical signal in bone remodeling. This is done in
      real time using the fluorescent chromophore DAR-4M AM. Differences in cellular
      response to mechanical stimulation of different regions of a single cell were
      observed. INTRODUCTION: Osteocytes are the most abundant bone cells that are
      believed to be the mechanosensors of bone, responding to mechanical stresses in
      interstitial fluid flow through the canaliculi. Under mechanical load, chemical
      signals such as NO play a key role in the activity of osteoblasts/osteoclasts
      that regulate bone remodeling. Despite the importance of NO in signaling, its
      real-time detection has proved challenging. This is largely because of the short
      NO half-life (typically approximately 0.1-5 s). Here, we show the upregulation of
      intracellular NO production in single osteocytes under localized mechanical
      stimulation. MATERIALS AND METHODS: We used the chromophore DAR-4M AM for NO
      detection. This is loaded into surface-attached MLO-Y4 osteocyte-like and MC3T3
      E1 osteoblast-like cells that are subjected to a localized mechanical stimulation
      using optical tweezers or a microneedle tip. DAR-4M AM is membrane-permeable and
      chelates NO, forming a stable, fluorescent compound, which is visible with a
      rhodamine filter. RESULTS: Nonstimulated MLO-Y4 and MC3T3-E1 cells showed basal
      NO production levels, as indicated by a gradual increase in their fluorescence
      intensity. Localized mechanical stimulation of single MC3T3-E1 cells and MLO-Y4
      cells by optical tweezers (150-550 pN, 0.5-3 Hz, 1 minute) showed a nearly 15-30%
      increase, whereas MLO-Y4 cells stimulated by a microneedle (10-20 nN, 1 minute)
      showed nearly 15-16% increase relative to their nonstimulated state. Furthermore,
      stimulation of a single cell process by a microneedle resulted in a 2-10%
      increase in the fluorescence intensity. CONCLUSIONS: NO is essential for
      mechanically induced bone remodeling and is a meaningful parameter for measuring
      bone cell activation after mechanical loading. Here we show NO upregulation in
      individual bone cells after a localized mechanical stimulation. We also show that
      both the cell body and the cell processes might be involved in mechanosensing.
      This technique allows characterization of the mechanosensitivity of different
      parts of a single osteocyte. This opens up the possibility to uncover the
      complexities and function of single osteocytes in the dynamic process of bone
      remodeling.

PMID- 17002571
TI  - Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide
      treated postmenopausal women with osteoporosis.
AB  - Increases in lumbar spine BMD account for 30-41% of the vertebral fracture risk
      reduction with teriparatide treatment. The remaining fracture risk reduction is
      caused by improvements in non-BMD determinants of bone strength. INTRODUCTION:
      Changes in BMD account for a small percentage of the fracture risk reduction seen
      in patients treated with antiresorptive drugs. The relationship between changes
      in lumbar spine BMD and vertebral fracture risk reduction with teriparatide
      treatment has not been assessed. MATERIALS AND METHODS: The relationship between
      spine BMD and the risk of new vertebral fractures after teriparatide treatment
      was assessed using data from the Fracture Prevention Trial. Postmenopausal women
      with osteoporosis (n = 1637) were randomized to placebo or teriparatide 20 or 40
      microg/day for a median of 19 months. Spine BMD was assessed at baseline and 18
      months. Vertebrae whose fracture status changed during the trial were removed
      from the calculation of BMD. Baseline and endpoint lateral spine radiographs were
      assessed using a visual semiquantitative technique. RESULTS: Both the baseline
      and change in spine BMD were contributors to vertebral fracture risk. The mean
      spine BMD increase in teriparatide-treated patients was 0.09 g/cm(2) across
      tertiles of baseline spine BMD. Compared with placebo, teriparatide significantly
      reduced the risk of new vertebral fracture for all endpoint BMD values.
      Teriparatide-mediated increases in spine BMD accounted for 30% (in the low
      baseline spine BMD tertile) to 41% (in the high baseline spine BMD tertile) of
      the reduction in vertebral fracture risk. CONCLUSIONS: Increases in BMD account
      for approximately one third of the vertebral fracture risk reduction seen with
      teriparatide. The majority of the risk reduction, however, results from
      improvements in non-BMD determinants of bone strength.

PMID- 17002572
TI  - Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V
      to modulate Wnt activity.
AB  - We compared and contrasted the mechanism of action for the cysteine knot protein
      subfamily, Wise and Sost (Sclerostin). Our data suggest that functional
      interactions between Sost or Wise and LRP5/LRP6 have the potential to regulate
      bone deposition by modulating the Wnt pathway. INTRODUCTION: The human disease
      sclerosteosis exhibits an increase in bone mass thought to be caused by
      hyperactive osteoblasts. Sclerostin, SOST, the gene affected in this disease, has
      been postulated to exert its activity by functioning as a BMP antagonist.
      However, recent evidence indicates that SOST is highly related to Wise, which can
      also modulate the Wnt pathway by binding to LRP5 and LRP6. MATERIALS AND METHODS:
      For this study, we used cell culture to test the BMP and Wnt activity function of
      both Wise and Sost. In addition, we used Xenopus in vivo Wnt assays along with
      Xenopus in vitro Wnt assays to support our cell culture results. Epitope tagged
      cell supernatants containing either Sost or soluble mutant or wildtype LRP5/LRP6
      were used for immunoprecipitation. Sost immunoprecipitation results were
      confirmed in vivo using cell culture. Finally, to support our in vitro data, we
      co-localized Sost, Wise, LRP5, and LRP6 in mouse long bone sections. RESULTS: In
      this study, we report in vitro and in vivo evidence to show that Sost physically
      interacts with Lrp5 and Lrp6 and inhibits the canonical Wnt signaling pathway.
      Furthermore, using in vitro and in vivo assays, we showed that a variant of LRP5
      (LRP5(G171V)) known to cause the human high bone mass (HBM) trait and a
      homologous change in LRP6 (LRP6(G158V)) abolished protein interactions with Sost.
      We used variants of Sost amino acids to further identify the contact points
      between Sost and LRP6. In Xenopus and mammalian cell culture assays, we showed
      that SOST is able to attenuate Wnt signaling and that this attenuation can be
      rescued by the addition of alpha-Sost antibodies or by the introduction of single
      amino acid substitution that alter its binding to LRP6. Sost differs from Wise in
      that it is unable to stimulate Wnt signaling. Using immunohistochemistry, we
      found that Sost and Wise are co-localized to osteoblasts, along with LRP5 and
      LRP6. CONCLUSIONS: Our data suggest that functional interactions between Sost or
      Wise and LRPs have the potential to regulate bone deposition by modulating Wnt
      signaling.

PMID- 17002573
TI  - Accentuated ovariectomy-induced bone loss and altered osteogenesis in
      heterozygous N-cadherin null mice.
AB  - Ovariectomy-induced bone loss is accentuated in mice with germline Cdh2
      haploinsufficiency, the result of a decreased osteoblastogenesis in the face of
      normal osteoclast number. Reduced N-cadherin abundance in these mice decreases
      cell-cell adhesion and alters signaling pathways important for osteoblast
      commitment and differentiation, thus providing in vivo evidence that N-cadherin
      mediated cell-cell interactions are involved in homeostatic responses to
      increased bone remodeling. INTRODUCTION: We have shown that targeted expression
      of a dominant negative truncated form of N-cadherin (Cdh2) delays acquisition of
      peak bone mass in mice and retards osteoblast differentiation. We tested the role
      of this molecule in the skeletal homeostatic response to ovariectomy in mice with
      germline Cdh2 haploinsufficiency. MATERIALS AND METHODS: Heterozygous Cdh2 null
      (Cdh2+/-) and wildtype mice were ovariectomized and followed up to 13 weeks by in
      vivo radiodensitometric and ex vivo histologic assessment of bone mass and
      turnover. Cells isolated from wildtype and Cdh2+/- mice were used to determine
      the alterations in bone cell function produced by partial loss of N-cadherin.
      RESULTS: Bone mass was not significantly different between Cdh2+/- and wildtype
      littermates, but on ovariectomy, bone loss in Cdh2+/- mice was initially slower,
      but with time it became significantly greater than in wildtype mice. This
      accentuated bone loss was associated with lower osteoblast number and serum
      osteocalcin levels, with no differences in bone resorption. Although development
      of calcified nodules was faster in calvaria cells isolated from Cdh2+/- mice
      relative to Cdh2+/+ cells, bone marrow osteogenic precursors were lower in the
      former than in the latter genotypes. Cdh2 expression was downregulated with
      differentiation in wildtype calvaria cells, whereas cadherin-11 abundance
      remained unchanged. Furthermore, cell-cell adhesion (postconfluence) was
      decreased among heterozygous calvaria cells, as was cell proliferation
      (preconfluence), relative to wildtype cells. Finally, the abundance and cellular
      distribution of beta-catenin was minimally decreased in Cdh2+/- cells, whereas
      mitogen-activated protein kinase (MAPK) signaling was more active in Cdh2
      insufficient cells. CONCLUSIONS: Cdh2 is involved in the homeostatic bone
      formation response to ovariectomy, presumably by regulating osteoprogenitors
      number and differentiation through stabilization of cell-cell adhesion and/or
      signaling modulation.

PMID- 17002574
TI  - 25-Hydroxyvitamin D deficiency and diabetes predict reduced BMD in patients with
      chronic kidney disease.
AB  - In this study of 242 patients with renal failure, women, patients with diabetes,
      and patients on peritoneal dialysis had the highest risk of 25-hydroxyvitamin D
      deficiency. Levels correlated positively to BMD Z scores, and hip BMD was
      inversely related to prevalent fracture. Increasing 25-hydroxyvitamin D levels
      may benefit these patients. INTRODUCTION: 25-Hydroxyvitamin D deficiency (<37 nM)
      is common in patients with chronic kidney disease (CKD) stage 5 (glomerular
      filtration rate < 15 ml/min/1.73 m(2) or on dialysis), but it is unclear if this
      deficiency is associated with bone disease and if supplementation is warranted.
      MATERIALS AND METHODS: Blood samples were collected on 242 patients with CKD
      stage 5 caused by type 1 diabetes (33%), type 2 diabetes (2%), and other causes
      (65%), who were about to undergo kidney or kidney pancreas transplantation.
      Prevalent spinal fracture was assessed by X-ray and BMD by DXA. RESULTS: 25
      Hydroxyvitamin D deficiency was present in 28% of patients with diabetes versus
      12% without (p < 0.0001). Patients on peritoneal dialysis (PD) had lower levels
      of 25-hydroxyvitamin D than patients on hemodialysis (HD; 49 +/- 26 versus 77 +/-
      34 nM; p < 0.0001), and women had lower levels than men (51 +/- 25 versus 77 +/-
      35 pM; p < 0.0001). BMD Z scores were within 1 SD of the mean at all sites,
      except in patients with diabetes (femoral neck Z score, -1.07 +/- 1.2; p <
      0.0001) and patients who had undergone parathyroidectomy (lumbar spine Z score,
      1.03 +/- 1.34, femoral neck Z score, 1.24 +/- 1.35; p < 0.001 and p < 0.0001,
      respectively). In multiple stepwise linear regression analysis, levels of 25
      hydroxyvitamin D correlated positively and intact PTH (iPTH) correlated
      negatively to Z scores at the lumbar spine and wrist. Time on dialysis correlated
      positively to Z scores at the femoral neck and lumbar spine. Diabetes and serum
      alkaline phosphatase levels correlated negatively with Z scores at the femoral
      neck. Lower femoral neck BMD was associated with an increased prevalence of
      vertebral fracture and fragility fracture at any site (p = 0.03 and p < 0.03,
      respectively). CONCLUSIONS: This study of patients with CKD stage 5 identifies
      women, patients with diabetes, and patients on PD as being at particular risk of
      25-hydroxyvitamin D deficiency. We describe positive associations of 25
      hydroxyvitamin D levels and BMD Z scores and an association between femoral neck
      BMD and fragility fracture at any site. Treatment to improve 25-hydroxyvitamin D
      levels may benefit these patients.

PMID- 17002575
TI  - Vertebral endplate fractures: an indicator of the abnormal forces generated in
      the spine after vertebroplasty.
AB  - Vertebroplasty alters spinal biomechanics and may lead to incident vertebral
      fractures. The endplate localization of prevalent and incident fractures was
      evaluated in 86 patients. In the absence of vertebroplasty, superior endplate
      fractures predominate. After the procedure, inferior endplate fractures are
      disproportionately common in adjacent vertebrae immediately above the treated
      level, potentially supporting a causative relationship between vertebroplasty and
      incident fractures. INTRODUCTION: To determine retrospectively whether new-onset
      fractures after vertebroplasty tend to cluster in the endplate immediately
      adjacent to the cemented vertebra. MATERIALS AND METHODS: Institutional Review
      Board approval and patient consent for use the use of medical records were
      obtained for this study. We performed a retrospective review of patients with new
      (incident) vertebral fractures after vertebroplasty. The median age for these
      patients was 72.5 years, and 58 (67.4%) were women. Fractures were diagnosed on
      the basis of MRI or bone scan and were catalogued based on their location within
      the vertebral body (superior endplate, inferior endplate, or holo-vertebral).
      Chi(2) and generalized estimating equation (GEE) analyses were used to compare
      the distribution of fracture subtypes among pre-existing (prevalent) and incident
      fractures. RESULTS: The patients had 313 prevalent osteoporotic vertebral
      fractures and were treated at 137 vertebral levels. Among prevalent fractures,
      superior endplate fractures predominated (57% superior, 11% inferior; p <
      0.0001). After vertebroplasty, 186 incident fractures developed in these 86
      patients. Seventy-seven (41%) of these incident fractures occurred adjacent to
      treated vertebrae. Nonadjacent, incident fractures, like prevalent fractures,
      occurred predominantly along superior endplate. Incident fractures immediately
      above treated levels, however, localized disproportionately to the inferior
      endplate (30% superior, 57% inferior; p < 0.0001). CONCLUSIONS: There are an
      increased number of inferior endplate fractures of the vertebral body immediately
      cephalad to the treated level.

PMID- 17002576
TI  - RANKL inhibition: a novel strategy to decrease femoral head deformity after
      ischemic osteonecrosis.
AB  - A novel therapeutic strategy to decrease the development of femoral head
      deformity after ischemic osteonecrosis was studied in a large animal model of
      total head infarction. RANKL inhibition through exogenous osteoprotegerin
      administration significantly decreased pathologic bone resorption and deformity
      during repair of the infarcted head. INTRODUCTION: Legg-Calve-Perthes disease
      (LCPD) is a juvenile form of osteonecrosis of the femoral head that can produce
      permanent femoral head deformity (FHD) and premature osteoarthritis. The
      development of FHD in LCPD is closely associated with the repair process,
      characterized by a predominance of bone resorption in its early stage that
      produces a fragmented appearance and collapse of the femoral head. We present
      here a novel strategy to preserve the femoral head structure after ischemic
      osteonecrosis based on inhibition of interaction between RANK and RANKL using
      exogenous administration of osteoprotegerin (OPG-Fc) in a large animal model of
      ischemic osteonecrosis. MATERIALS AND METHODS: Ischemic osteonecrosis was
      surgically induced in 18 male piglets by placing a ligature tightly around the
      right femoral neck to disrupt the blood flow to the right femoral head. Two weeks
      after the induction of total head infarction, OPG-Fc or saline was administered
      subcutaneously to nine animals per group for 6 weeks. The contralateral, normal
      (left) femoral heads from the animals treated with saline served as normal,
      nondisease controls. All animals were killed at 8 weeks when severe FHD has been
      previously shown to occur because of the repair process dominated by osteoclastic
      bone resorption. Radiographic, histomorphometric, and immunohistochemical
      assessments were performed. RESULTS: Radiographic assessment showed significantly
      better preservation of the femoral head structure in the OPG-Fc group compared
      with the saline group. Epiphyseal quotient (the ratio of epiphyseal height to
      diameter) was significantly higher in the OPG-Fc group (0.41 +/- 0.09) compared
      with the saline group (0.24 +/- 0.08, p < 0.001). Histomorphometric assessment
      revealed a significant reduction in the number of osteoclasts present in the OPG
      Fc group (5.9 +/- 5.3mm(-2)) compared with the saline group (39.6 +/- 13.8 mm(
      2), p < 0.001). Trabecular bone volume, number, and separation were significantly
      better preserved in the OPG-Fc group compared with the saline group (p < 0.001).
      No significant difference in femoral length was observed between the OPG-Fc and
      saline groups. Immunostaining revealed the presence of OPG-Fc only within the
      blood vessels, with no apparent staining of bone matrix or trabecular bone
      surfaces. CONCLUSIONS: To our knowledge, this is the first study to show that
      RANKL inhibition decreases bone resorption and FHD after ischemic osteonecrosis.
      Because RANKL inhibitors do not bind to bone, their effects on resorption are
      reversible as the drug is cleared from circulation. The reversible nature of
      RANKL inhibitors is very appealing for treating pediatric bone diseases such as
      LCPD, where the resorptive stage of the disease lasts for 1-2 years.

PMID- 17002577
TI  - Canine distemper virus induces human osteoclastogenesis through NF-kappaB and
      sequestosome 1/P62 activation.
AB  - Previous studies have implicated CDV in the pathogenesis of Paget's disease;
      however, there has been no direct evidence that CDV can infect human cells. We
      studied the effects of CDV on osteoclastogenesis in vitro and showed that CDV had
      a dose-dependent effect on osteoclastogenesis, through a possible mechanism
      involving activation of NF-kappaB and sequestosome 1/p62. INTRODUCTION: Paget's
      disease is characterized by a dramatic increase in size and number of
      osteoclasts. The etiology of the disorder is still unclear; however, evidence
      points to either a viral infection or a genetic susceptibility or a combination
      of both. Previously, we have shown that canine distemper virus (CDV) RNA is
      present in Pagetic bone. However, the effects of CDV on human osteoclast
      formation in vitro have not been studied previously. MATERIALS AND METHODS:
      Replicate cultures (n = 5) of purified human osteoclast precursors were infected
      with increasing doses of CDV and cultured on dentine slices for 14 days.
      Osteoclasts were stained for TRACP, and the dentine slices were examined for
      evidence of resorption. Control cells were incubated in the absence of virus. In
      each case, 10 high-power microscopy fields were analyzed. Immunocytochemical
      analyses were performed for p65, Gab2, sequestosome 1/p62, and ubiquitin.
      RESULTS: CDV dose-dependently increased osteoclast number and size (p < 0.0001,
      ANOVA), and there was a concomitant increase in resorption (p < 0.0001, ANOVA).
      CDV infection induced nuclear translocation of p65 and led to a dramatic increase
      in sequestosome 1/p62 and ubiquitin expression. CONCLUSIONS: These results
      provide the first conclusive proof that CDV can infect and replicate in human
      osteoclast precursors, raising possible zoonotic implications for CDV. The
      increased osteoclastogenesis is accompanied by NF-kappaB and sequestosome 1/p62
      activation. This study provides further evidence for the possible role of
      paramyxoviruses in the pathogenesis of Paget's disease.

PMID- 17002578
TI  - Nationwide decline in incidence of hip fracture.
AB  - This epidemiologic study determined the trend in the number and incidence (per
      100,000 persons) of hip fracture among older adults in Finland, an EU country
      with a well-defined white population of 5.2 million, between 1970 and 2004. The
      results show that the alarming rise in the fracture incidence from early 1970s
      until late 1990s has been now followed by declining fracture rates. Reasons for
      this are largely unknown, but a cohort effect toward a healthier aging population
      and increased average body weight and improved functional ability among elderly
      Finns could partly explain the phenomenon. INTRODUCTION: Although osteoporotic
      fractures of older adults are said to be a major public health concern in modern
      societies with aging populations, fresh nationwide information on their secular
      trends is limited. MATERIALS AND METHODS: This epidemiologic study determined the
      current trend in the number and incidence (per 100,000 persons) of hip fracture
      among older adults in Finland, an EU country with a well-defined white population
      of 5.2 million, by taking into account all persons >or= 50 years of age who were
      admitted to our hospitals for primary treatment of such fracture in 1970-2004.
      RESULTS: The number of hip fractures among >or= 50-year-old Finns rose very
      constantly between 1970 (1857 fractures) and 1997 (7122 fractures), but since
      then, the rise has leveled off (7083 fractures in 2004). After this and because
      of a continuous rise in population at risk, the crude incidence of hip fracture
      (showing a clear rise in 1970-1997) decreased between 1997 and 2004, from 438
      (per 100,000 persons) in 1997 to 374 in 2004. Concerning the age-adjusted
      fracture incidence, findings were similar. Until 1997, the age-adjusted incidence
      of hip fracture clearly increased in both women and men, but thereafter, this
      incidence declined in both sexes: in women, from 494 in 1997 to 412 in 2004, and
      in men, from 238 in 1997 to 223 in 2004. CONCLUSIONS: The rise in the incidence
      of hip fracture in Finland from the early 1970s until the late 1990s has been
      followed by declining fracture rates. Exact reasons for this are unknown, but a
      cohort effect toward a healthier aging population and increased average body
      weight and improved functional ability among elderly Finns cannot be ruled out.

PMID- 17002579
TI  - PTH-induced actin depolymerization increases mechanosensitive channel activity to
      enhance mechanically stimulated Ca2+ signaling in osteoblasts.
AB  - Disruption of the actin cytoskeleton with cytochalasin D enhanced the
      mechanically induced increase in intracellular Ca(2+) ([Ca(2+)](i)) in
      osteoblasts in a manner similar to that of PTH. Stabilization of actin with
      phalloidin prevented the PTH enhanced [Ca(2+)](i) response to shear. Patch-clamp
      analyses show that the MSCC is directly influenced by alterations in actin
      integrity. INTRODUCTION: PTH significantly enhances the fluid shear-induced
      increase in [Ca(2+)](i) in osteoblasts, in part, through increased activation of
      both the mechanosensitive, cation-selective channel (MSCC) and L-type voltage
      sensitive Ca(2+) channel (L-VSCC). Both stimuli have been shown to produce
      dynamic changes in the organization of the actin cytoskeleton. In this study, we
      examined the effects of alterations in actin polymerization on [Ca(2+)](i) and
      MSCC activity in MC3T3-E1 and UMR-106.01 osteoblasts in response to shear +/- PTH
      pretreatment. MATERIALS AND METHODS: MC3T3-E1 or UMR-106.01 cells were plated
      onto type I collagen-coated quartz slides, allowed to proliferate to 60%
      confluency, and mounted on a modified parallel plate chamber and subjected to 12
      dynes/cm(2). For patch-clamp studies, cells were plated on collagen-coated glass
      coverslips, mounted on the patch chamber, and subjected to pipette suction.
      Modulators of actin cytoskeleton polymerization were added 30 minutes before the
      experiments, whereas channel inhibitors were added 10 minutes before mechanical
      stimulation. All drugs were maintained in the flow medium for the duration of the
      experiment. RESULTS AND CONCLUSIONS: Depolymerization of actin with 1-5 microM
      cytochalasin D (cyto D) augmented the peak [Ca(2+)](i) response and increased the
      number of cells responding to shear, similar to the increased responses induced
      by pretreatment with 50 nM PTH. Stabilization of actin with phalloidin prevented
      the PTH enhanced [Ca(2+)](i) response to shear. Inhibition of the MSCC with
      Gd(3+) significantly blocked both the peak Ca(2+) response and the number of
      cells responding to shear in cells pretreated with either PTH or cyto D.
      Inhibition of the L-VSCC reduced the peak [Ca(2+)](i) response to shear in cells
      pretreated with PTH, but not with cyto D. Patch-clamp analyses found that
      addition of PTH or cyto D significantly increased the MSCC open probability in
      response to mechanical stimulation, whereas phalloidin significantly attenuated
      the PTH-enhanced MSCC activation. These data indicate that actin reorganization
      increases MSCC activity in a manner similar to PTH and may be one mechanism
      through which PTH may reduce the mechanical threshold of osteoblasts.

PMID- 17002580
TI  - Bone fragility: failure of periosteal apposition to compensate for increased
      endocortical resorption in postmenopausal women.
AB  - The increase in bone fragility after menopause results from reduced periosteal
      bone formation and increased endocortical resorption. Women with highest
      remodeling had greatest loss of bone mass and estimated bone strength, whereas
      those with low remodeling lost less bone and maintained estimated bone strength.
      INTRODUCTION: Bone loss from the inner (endocortical) surface contributes to bone
      fragility, whereas deposition of bone on the outer (periosteal) surface is
      believed to be an adaptive response to maintain resistance to bending. MATERIALS
      AND METHODS: To test this hypothesis, changes in bone mass and estimated indices
      of bone geometry and strength of the one-third distal radius, bone turnover
      markers, and fracture incidence were measured annually in 821 women 30-89 years
      of age for 7.1 +/- 2.5 years. The analyses were made in 151 premenopausal women,
      33 perimenopausal women, 279 postmenopausal women, and 72 postmenopausal women
      receiving hormone replacement therapy (HRT). RESULTS: In premenopausal women,
      periosteal apposition increased the radius width, partly offsetting endocortical
      resorption; therefore, the estimated cortical thickness decreased. Outward
      displacement of the thinner cortex maintained bone mass and cortical area and
      increased estimated bending strength. Estimated endocortical resorption
      accelerated during perimenopause, whereas periosteal apposition decreased.
      Further cortical thinning occurred, but estimated bending strength was maintained
      by modest outward cortical displacement. Endocortical resorption accelerated
      further during the postmenopausal years, whereas periosteal apposition declined
      further; cortices thinned, but because outward displacement was minimal,
      estimated cortical area and bending strength now decreased. Women with highest
      remodeling had the greatest loss of bone mass and strength. Women with low
      remodeling lost less bone and maintained estimated bone strength. In HRT-treated
      women, loss of bone strength was partly prevented. These structural indices
      predicted incident fractures; a 1 SD lower section modulus doubled fracture risk.
      CONCLUSIONS: Periosteal apposition does not increase after menopause to
      compensate for bone loss; it decreases. Bone fragility of osteoporosis is a
      consequence of reduced periosteal bone formation and increased endocortical
      resorption. Understanding the mechanisms of the age-related decline in periosteal
      apposition will identify new therapeutic targets. On the basis of our results, it
      may be speculated that the stimulation of periosteal apposition will increase
      bone width and improve skeletal strength.

PMID- 17002581
TI  - CYP1A1: ethnic and population differences in allelic frequencies and
      interpretation of bone biology studies.

PMID- 17002582
TI  - Calcium channel TRPV6 expression in human duodenum: different relationships to
      the vitamin D system and aging in men and women.
AB  - Intestinal absorption of calcium affects bone mineralization and varies greatly.
      In human duodenum, expression of the calcium channel TRPV6 was directly related
      to blood 1,25-dihydroxyvitamin D in men, but effects of age with lower median
      vitamin D receptor levels were more significant in women. INTRODUCTION: The TRPV6
      calcium channel/transporter is implicated in animal studies of intestinal calcium
      absorption, but in humans, its role and relationship to differences in mineral
      metabolism is unclear. We aimed to characterize TRPV6 expression in human
      intestine including defining relationships to the vitamin D endocrine system.
      MATERIALS AND METHODS: TRPV6 transcript expression was determined in endoscopic
      mucosal biopsies obtained from normal duodenum. Expression was compared with that
      in ileum and with in situ hybridization in archival tissues and related to
      sequence variants in genomic DNA. TRPV6 expression was related in 33 subjects to
      other transcripts involved in calcium absorption including the vitamin D receptor
      (VDR) and to blood vitamin D metabolites including 1,25-dihydroxyvitamin D
      [1,25(OH)(2)D]. RESULTS: TRPV6 transcripts were readily detected in duodenum but
      not in ileum. Expression was highest in villous epithelial cells. Sequence
      variants in the coding and upstream regions of the gene did not affect TRPV6
      expression. The relationship between duodenal TRPV6 expression and 1,25(OH)(2)D
      differed in men and women. In men, linear regression showed a strong association
      with 1,25(OH)(2)D (r = 0.87, p < 0.01), which was unaffected by age. In women,
      there was no significant overall relationship with 1,25(OH)(2)D, but there was a
      significant decrease with age (r = -0.69, p < 0.001). Individual expression of
      TRPV6 and VDR was significantly correlated. The group of older women (>50) had
      lower median levels of both TRPV6 and VDR transcripts than younger women (p <
      0.001 and 0.02, respectively). CONCLUSIONS: Duodenal TRPV6 expression is vitamin
      D dependent in men, but not in older women, where expression of TRPV6 and VDR are
      both reduced. These findings can explain, at least in part, the lower fractional
      calcium absorption seen in older postmenopausal women.

PMID- 17002583
TI  - QTL with pleiotropic effects on serum levels of bone-specific alkaline
      phosphatase and osteocalcin maps to the baboon ortholog of human chromosome 6p23
      21.3.
AB  - Bone ALP and OC are under partial genetic control. This study of 591 pedigreed
      baboons shows a QTL corresponding to human 6p23-21.3 that accounts for 25% (bone
      ALP) and 20% (OC) of the genetic variance. A gene affecting osteoblast activity,
      number, or recruitment likely resides in this area. INTRODUCTION: Serum levels of
      bone alkaline phosphatase (ALP) and osteocalcin (OC) reflect osteoblast activity.
      Both of these measures are under partial genetic control. Genetic effects on bone
      ALP have not been previously localized to chromosomal regions in primates, nor
      has the degree to which genetic effects are shared (pleiotropic) between bone ALP
      and OC been studied. MATERIALS AND METHODS: We applied variance components
      methods to a sample of 591 adult pedigreed baboons to detect and quantify effects
      of genes that influence bone ALP and that have pleiotropic effects on bone ALP
      and OC. A univariate linkage analysis was conducted for bone ALP. Bivariate
      linkage analyses were conducted in areas for which the bone ALP results presented
      here and a previous univariate OC linkage analysis showed evidence for linkage on
      the same chromosome for both bone ALP and OC. RESULTS: A quantitative trait locus
      (QTL) for serum levels of bone ALP is evident on the baboon ortholog of human
      chromosomal region 6p (LOD 2.93). Thirty-seven percent (genetic correlation
      [rho(G)] = 0.61) of the genetic variance in bone ALP and OC is caused by
      pleiotropic effects of the same gene(s). Bivariate linkage analysis revealed a
      QTL in the region corresponding to human chromosome 6p23-21.3, with the strongest
      evidence for bivariate linkage near D6S422 (LOD = 2.97 at 22 cM from our pter
      most marker). D6S422 maps to 20.4 Mb in the human genome. The QTL-specific
      heritability (h2) is 0.25 and 0.20 for bone ALP and OC, respectively.
      CONCLUSIONS: This first formal test for shared genetic effects on two serum
      markers of osteoblast activity indicates that a significant pleiotropic effect on
      bone ALP and OC levels, and thus on bone formation, is detectible. The fact that
      this region corresponds to one on mouse chromosome 13 that has repeatedly yielded
      QTLs for BMD should encourage more intensive study of the effect of genes in this
      region on bone maintenance and turnover.

PMID- 17002584
TI  - Independent and combined contributions of cancellous and cortical bone deficits
      to vertebral fracture risk in postmenopausal women.
AB  - Using iliac bone histomorphometry on 78 patients with vertebral fracture and 66
      healthy postmenopausal women, cortical thickness discriminated at least as well
      as any cancellous bone structural index between the two groups. Subjects with a
      deficit in both cortical and cancellous bone had much greater likelihood of
      fracture. INTRODUCTION: Vertebral fracture is often attributed to disproportional
      loss of cancellous bone, but fracture patients may have deficits in cortical and
      cancellous bone. Accordingly, we examined the contribution of cortical and
      cancellous bone deficits, separately and together, to the likelihood of vertebral
      fracture. MATERIALS AND METHODS: Iliac bone histomorphometry was performed in 78
      white woman with clinically apparent vertebral fracture, 66 healthy
      postmenopausal women, and 38 healthy premenopausal women. We measured cancellous
      bone volume (Cn.BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th),
      cortical bone volume (Ct.BV/TV), and cortical thickness (Ct.Th). For each
      variable, a value of >1 SD below the mean in premenopausal women was treated as a
      putative risk factor, and its association with the presence or absence of
      fracture was determined by OR calculated by logistic regression and by receiver
      operating characteristic (ROC) curve analysis. Subsets of fracture and control
      subjects were separately matched for Cn.BV/TV and Ct.Th. RESULTS: All structural
      indices differed between fracture patients and controls except Ct.BV/TV. There
      was a weak but highly significant correlation between Cn.BV/TV and Ct.Th in the
      entire group (r = 0.389, r(2) = 0.151 p < 0.001). Many control subjects had a
      high value for one of these variables and a low value for the other. Ct.Th.,
      Cn.BV/TV, and Tb.N were all significantly associated with vertebral fracture
      (ORs, 4.4-5.8; ROC area under the curve [AUC], 0.74-0.85). In subjects matched
      for Cn.BV/TV, Ct.Th was reduced by 29% (OR, 5.0), and in subjects matched for
      Ct.Th, Cn.BV/TV was reduced by 27% (OR, 5.0). In patients with deficits in both
      cortical and cancellous bone, the ORs ( 28-35 ) were much higher. CONCLUSIONS:
      Deficits in cortical bone (reduced value for Ct.Th) and in cancellous bone
      (reduced values for Cn.BV/TV or Tb.N) were equally effective in discriminating
      between subjects with and without vertebral fracture. With a deficit in both
      cortical and cancellous bone, the association with vertebral fracture was much
      stronger. Vertebral fracture is not the result of disproportionate loss of
      cancellous bone in the patients as a whole, although individual patients may have
      relatively greater deficits in either cancellous or cortical bone.

PMID- 17002585
TI  - Secreted frizzled-related protein 4 is a negative regulator of peak BMD in SAMP6
      mice.
AB  - We segregated a QTL for peak BMD on Chr 13 by generating congenic sublines of the
      senescence-accelerated mouse SAMP6. Sfrp 4 within this locus was responsible for
      lower BMD of SAMP6. INTRODUCTION: Our genome-wide linkage study using SAMP6 and
      SAMP2 showed a significant quantitative trait locus (QTL) for peak BMD on
      chromosome (Chr) 13. To verify the gene that regulates peak BMD, we generated a
      congenic strain, P6.P2-Pbd2(b), which carried a 15-cM SAMP2 interval on an
      osteoporotic SAMP6 background, and showed that this Pbd2 locus increased peak BMD
      in SAMP6. MATERIALS AND METHODS: To narrow down this interval, we generated a new
      congenic subline P6.P2-13. We studied the effect of this locus on morphological
      and histomorphological features in vivo and on osteoblasts in vitro. The levels
      of expression of all genes in the segregated interval were examined, and we
      clarified the effect of the candidate gene, secreted frizzled-related protein
      (Sfrp4), on osteoblasts in vitro. RESULTS: The new congenic strain, P6.P2-13,
      retained the 2.4-Mb SAMP2 interval on the SAMP6 background, and 11 genes existed
      in this interval. In morphometrical analysis, P6.P2-13 increased the bone area
      fraction (BA/TA) by 6.6% at the diaphysial cortex (p < 0.001) and increased the
      trabecular bone volume (BV/TV) by 54.2% at the distal metaphysis (p < 0.05) in
      the femora compared with those of SAMP6. The bone formation rate of P6.P2-13 was
      markedly increased at the periosteal surface of femoral cortex and that was
      caused by a higher proliferation rate of osteoblasts in P6.P2-13 compared with
      those in SAMP6. Quantitative RT-PCR analysis of calvaria tissue showed
      approximately 40-fold higher levels of expression of Sfrp4 in SAMP6 than in P6.P2
      13. Taken together with the result that recombinant Sfrp4 suppressed the
      proliferation of osteoblasts, we hypothesized that Sfrp4 inhibited the
      proliferation of osteoblasts through its antagonistic effect on Wnt signaling.
      TCF/beta-catenin-dependent reporter activity in osteoblasts derived from SAMP6
      showed lower responsiveness for the Wnt ligand, Wnt3A, than that in osteoblasts
      from P6.P2-13. CONCLUSIONS: In SAMP6 mice, Sfrp4 negatively regulates bone
      formation and decreases BMD through the inhibition of Wnt signaling.

PMID- 17002586
TI  - Enhanced osteoclastogenesis in 4-1BB-deficient mice caused by reduced interleukin
      10.
AB  - Enhanced osteoclastogenesis was observed in bone marrow-derived macrophage cells
      from 4-1BB-deficient mice than in those from wildtype mice. 4-1BB and 4-1BB
      ligand interaction may play a role at a certain stage of osteoclast formation
      through increased level of IL-10, a negative regulator of osteoclastogenesis.
      INTRODUCTION: 4-1BB is an inducible T-cell costimulatory molecule and a member of
      the TNF receptor family. The expression pattern of 4-1BB and 4-1BB ligand (4
      1BBL) has suggested that 4-1BB plays a role not only in various responses related
      to innate immunity but also in bone metabolism. MATERIALS AND METHODS: Osteoclast
      formation was evaluated in bone marrow-derived macrophage cells (BMMs) from
      wildtype and 4-1BB-deficient (4-1BB-/-) mice. Expression of interleukin-10 (IL
      10) during osteoclast formation was analyzed at the mRNA and protein levels.
      RESULTS: Expression of IL-10 was higher in RANKL-stimulated wildtype BMMs than 4
      1BB-/- BMMs. When 4-1BBL was stimulated with 4-1BB-Fc fusion protein, the
      expression of IL-10 in BMMs increased. Neutralization of IL-10 was not as
      effective in preventing inhibition by IL-10 of osteoclast differentiation in 4
      1BB-/- BMMs as in wildtype BMMs. When IL-10 was added to the culture medium,
      osteoclast formation was inhibited more efficiently in the 4-1BB-/- BMMs than in
      the wildtype BMMs. CONCLUSIONS: Interaction of 4-1BB and 4-1BBL stimulates IL-10
      production through 4-1BBL signaling. 4-1BBL plays a role at a certain stage of
      osteoclast formation, and IL-10 may mediate this effect. The elevated level of
      osteoclastogenesis in 4-1BB-/- BMMs may thus be caused, in part, by a lower level
      of IL-10.

PMID- 17002587
TI  - Calcitonin deficiency in mice progressively results in high bone turnover.
AB  - Although the pharmacological action of calcitonin (CT) as an inhibitor of bone
      resorption is well established, there is still some controversy regarding its
      physiological function. Unexpectedly, Calca-deficient mice lacking CT and alpha
      calcitonin gene-related peptide (alphaCGRP) were described to have a high bone
      mass phenotype caused by increased bone formation with normal bone resorption.
      Here we show that these mice develop a phenotype of high bone turnover with age,
      suggesting that CT is a physiological inhibitor of bone remodeling. INTRODUCTION:
      The absence of significant changes in bone mineral density caused by decline or
      overproduction of CT in humans has raised the question, whether the
      pharmacological action of CT as an inhibitor of bone resorption is also of
      physiological relevance. To study the physiological role of mammalian CT, we have
      analyzed the age-dependent bone phenotype of two mouse models, one lacking CT and
      alphaCGRP (Calca-/-), the other one lacking only alphaCGRP (alphaCGRP-/-).
      MATERIALS AND METHODS: Bones from wildtype, Calca-/- -mice and alphaCGRP-/- -mice
      were analyzed at the ages of 6, 12 and 18 months using undecalcified histology.
      Differences of bone remodeling were quantified by static and dynamic
      histomorphometry as well as by measuring the urinary collagen degradation
      products. To rule out secondary mechanisms underlying the observed phenotype, we
      determined serum concentrations of relevant hormones using commercially available
      antibody-based detection kits. RESULTS: Whereas alphaCGRP-/- -mice display an
      osteopenia at all ages analyzed, the Calca-/- -mice develop a phenotype of high
      bone turnover with age. Histomorphometric analysis performed at the age of 12
      months revealed significant increases of bone formation and bone resorption
      specifically in the Calca-/- -mice. This severe phenotype that can result in
      hyperostotic lesions, can not be explained by obvious endocrine abnormalities
      other than the absence of CT. CONCLUSIONS: In addition to the previously
      described increase of bone formation in the Calca-deficient mice, we have
      observed that there is also an increase of bone resorption with age. This
      suggests that CT has a dual action as an inhibitor of bone remodeling, which may
      explain why alterations of CT serum levels in humans do not result in major
      changes of bone mineral density.

PMID- 17002589
TI  - Size-corrected BMD decreases during peak linear growth: implications for fracture
      incidence during adolescence.
AB  - Peak adolescent fracture incidence at the distal end of the radius coincides with
      a decline in size-corrected BMD in both boys and girls. Peak gains in bone area
      preceded peak gains in BMC in a longitudinal sample of boys and girls, supporting
      the theory that the dissociation between skeletal expansion and skeletal
      mineralization results in a period of relative bone weakness. INTRODUCTION: The
      high incidence of fracture in adolescence may be related to a period of relative
      skeletal fragility resulting from dissociation between bone expansion and bone
      mineralization during the growing years. The aim of this study was to examine the
      relationship between changes in size-corrected BMD (BMDsc) and peak distal radius
      fracture incidence in boys and girls. MATERIALS AND METHODS: Subjects were 41
      boys and 46 girls measured annually (DXA; Hologic 2000) over the adolescent
      growth period and again in young adulthood. Ages of peak height velocity (PHV),
      peak BMC velocity (PBMCV), and peak bone area (BA) velocity (PBAV) were
      determined for each child. To control for maturational differences, subjects were
      aligned on PHV. BMDsc was calculated by first regressing the natural logarithms
      of BMC and BA. The power coefficient (pc) values from this analysis were used as
      follows: BMDsc = BMC/BA(pc). RESULTS: BMDsc decreased significantly before the
      age of PHV and then increased until 4 years after PHV. The peak rates in radial
      fractures (reported from previous work) in both boys and girls coincided with the
      age of negative velocity in BMDsc; the age of peak BA velocity (PBAV) preceded
      the age of peak BMC velocity (PBMCV) by 0.5 years in both boys and girls.
      CONCLUSIONS: There is a clear dissociation between PBMCV and PBAV in boys and
      girls. BMDsc declines before age of PHV before rebounding after PHV. The timing
      of these events coincides directly with reported fracture rates of the distal end
      of the radius. Thus, the results support the theory that there is a period of
      relative skeletal weakness during the adolescent growth period caused, in part,
      by a draw on cortical bone to meet the mineral demands of the expanding skeleton
      resulting in a temporary increased fracture risk.

PMID- 17002590
TI  - Effects of strontium on bone strength, density, volume, and microarchitecture in
      laying hens.
AB  - Strontium has been reported to have beneficial effects on bone. Treatment of
      laying hens, which are susceptible to osteoporosis and bone fracture, with
      strontium increased DXA measurements of BMD and BMC and microCT measurements of
      bone volume and microarchitecture and improved the mechanical performance of
      whole bone, but had no effect on the estimated material properties of the bone
      tissue. INTRODUCTION: Strontium (Sr) has been reported to dissociate bone
      remodeling and have positive influences on bone formation. We supplemented the
      diet of laying hens, which are susceptible to osteoporosis and bone fracture,
      with Sr to study the capacity of the element to improve bone mechanical integrity
      and resistance to fracture. MATERIALS AND METHODS: Increasing dosages of Sr (0,
      3000, 4500, and 6000 ppm) were fed to 196 13-week-old pullets for 11 months. BMD
      and BMC, as measured by conventional and DXA methods, microarchitectural
      parameters derived from microCT, and structural and material properties as
      determined by three-point bending test, were studied. Calcium (Ca), phosphorus
      (P), and Sr levels in plasma and bone, as well as egg output, shell quality, and
      composition, were assessed. RESULTS: Sr concentrations in plasma and bone
      increased in a dose-dependent manner without affecting Ca and P. Treatment with
      Sr increased BMD and BMC as measured by DXA, increased cortical and medullary
      bone volume, trabecular thickness, number, and surface, and improved whole bone
      ultimate load, but had no effect on the estimated material properties of
      diaphyseal bone. Sr also increased the ash content of eggshells and did not
      affect egg output and shell quality. CONCLUSIONS: Sr supplementation induced
      large positive effects on bone density, volume, and microarchitecture as measured
      by radiographic methods. Sr treatment also improved the structural strength of
      diaphyseal bone but had no effect on the estimated material properties of the
      bone tissue.

PMID- 17002592
TI  - Phosphatonins and the regulation of phosphate homeostasis.
AB  - Inorganic phosphate (P(i)) is required for energy metabolism, nucleic acid
      synthesis, bone mineralization, and cell signaling. The activity of cell-surface
      sodium-phosphate (Na(+)-P(i)) cotransporters mediates the uptake of P(i) from the
      extracellular environment. Na(+)-P(i) cotransporters and organ-specific P(i)
      absorptive processes are regulated by peptide and sterol hormones, such as
      parathyroid hormone (PTH) and 1alpha,25-dihydroxyvitamin D
      (1alpha,25(OH)(2)D(3)), which interact in a coordinated fashion to regulate P(i)
      homeostasis. Recently, several phosphaturic peptides such as fibroblast growth
      factor-23 (FGF-23), secreted frizzled related protein-4 (sFRP-4), matrix
      extracellular phosphoglycoprotein, and fibroblast growth factor-7 have been
      demonstrated to play a pathogenic role in several hypophosphatemic disorders. By
      inhibiting Na(+)-P(i) transporters in renal epithelial cells, these proteins
      increase renal P(i) excretion, resulting in hypophosphatemia. FGF-23 and sFRP-4
      inhibit 25-hydroxyvitamin D 1alpha-hydroxylase activity, reducing
      1alpha,25(OH)(2)D(3) synthesis and thus intestinal P(i) absorption. This review
      examines the role of these factors in P(i) homeostasis in health and disease.

PMID- 17002593
TI  - Stop that cell! Beta-arrestin-dependent chemotaxis: a tale of localized actin
      assembly and receptor desensitization.
AB  - Beta-arrestins have recently emerged as key regulators of directed cell migration
      or chemotaxis. Given their traditional role as mediators of receptor
      desensitization, one theory is that beta-arrestins contribute to cell polarity
      during chemotaxis by quenching the signal at the trailing edge of the cell. A
      second theory is that they scaffold signaling molecules involved in cytoskeletal
      reorganization to promote localized actin assembly events leading to the
      formation of a leading edge. This review addresses both models. It discusses
      studies demonstrating the involvement of beta-arrestins in chemotaxis both in
      vivo and in vitro as well as recent evidence that beta-arrestins directly bind
      and regulate proteins involved in actin reorganization.

PMID- 17002591
TI  - Molecular mechanisms of renal ammonia transport.
AB  - Acid-base homeostasis to a great extent relies on renal ammonia metabolism. In
      the past several years, seminal studies have generated important new insights
      into the mechanisms of renal ammonia transport. In particular, the theory that
      ammonia transport occurs almost exclusively through nonionic NH(3) diffusion and
      NH(4)(+) trapping has given way to a model postulating that a variety of proteins
      specifically transport NH(3) and NH(4)(+) and that this transport is critical for
      normal ammonia metabolism. Many of these proteins transport primarily H(+) or
      K(+) but also transport NH(4)(+). Nonerythroid Rh glycoproteins transport ammonia
      and may represent critical facilitators of ammonia transport in the kidney. This
      review discusses the underlying aspects of renal ammonia transport as well as
      specific proteins with important roles in renal ammonia transport.

PMID- 17002594
TI  - Regulation of intestinal cholesterol absorption.
AB  - The identification of defective structures in the ATP-binding cassette (ABC)
      transporters ABCG5 and ABCG8 in patients with sitosterolemia suggests that these
      two proteins are an apical sterol export pump promoting active efflux of
      cholesterol and plant sterols from enterocytes back into the intestinal lumen for
      excretion. The newly identified Niemann-Pick C1-like 1 (NPC1L1) protein is also
      expressed at the apical membrane of enterocytes and plays a crucial role in the
      ezetimibe-sensitive cholesterol absorption pathway. These findings indicate that
      cholesterol absorption is a multistep process that is regulated by multiple genes
      at the enterocyte level and that the efficiency of cholesterol absorption may be
      determined by the net effect between influx and efflux of intraluminal
      cholesterol molecules crossing the brush border membrane of the enterocyte.
      Combination therapy using cholesterol absorption (NPC1L1) inhibitor (ezetimibe)
      and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins)
      provides a powerful novel strategy for the prevention and treatment of
      hypercholesterolemia.

PMID- 17002595
TI  - Regulation of receptor tyrosine kinase signaling by GRKs and beta-arrestins.
AB  - Receptor tyrosine kinases (RTKs) are a unique family of cell surface receptors,
      each containing a common intracellular domain that has tyrosine kinase activity.
      However, RTKs share many signaling molecules with another unique family of cell
      surface receptors, the seven-transmembrane receptors (7TMRs), and these receptor
      families can activate similar signaling cascades. In this review of RTK
      signaling, we describe the role of cross talk between RTKs and 7TMRs, focusing
      specifically on the role played in this process by beta-arrestins and by G
      proteins.

PMID- 17002596
TI  - Specificity and regulation of renal sulfate transporters.
AB  - Sulfate is essential for normal cellular function. The kidney plays a major role
      in sulfate homeostasis. Sulfate is freely filtered and then undergoes net
      reabsorption in the proximal tubule. The apical membrane Na(+)/sulfate
      cotransporter NaS1 (SLC13A1) has a major role in mediating proximal tubule
      sulfate reabsorption, as demonstrated by the findings of hyposulfatemia and
      hypersulfaturia in Nas1-null mice. The anion exchanger SAT1 (SLC26A1), the
      founding member of the SLC26 sulfate transporter family, mediates sulfate exit
      across the basolateral membrane to complete the process of transtubular sulfate
      reabsorption. Another member of this family, CFEX (SLC26A6), is present at the
      apical membrane of proximal tubular cells. It also can transport sulfate by anion
      exchange, which probably mediates backflux of sulfate into the lumen. Knockout
      mouse studies have demonstrated a major role of CFEX as an apical membrane Cl(
      )/oxalate exchanger that contributes to NaCl reabsorption in the proximal tubule.
      Several additional SLC26 family members mediate sulfate transport and show some
      level of renal expression (e.g., SLC26A2, SLC26A7, SLC26A11). Their roles in
      mediating renal tubular sulfate transport are presently unknown. This paper
      reviews current data available on the function and regulation of three sulfate
      transporters (NaS1, SAT1, and CFEX) and their physiological roles in the kidney.

PMID- 17002598
TI  - Arsenic: signal transduction, transcription factor, and biotransformation
      involved in cellular response and toxicity.
AB  - Arsenic is a naturally occurring metalloid that causes oxidative stress. Exposure
      of humans, experimental animals, and cultured cells to arsenic results in a
      variety of diverse health effects, dysfunction of critical enzymes, and cell
      damage. In this context, one area of arsenic study has been the role of its
      metabolism. Like organic chemicals, arsenic undergoes reduction, methylation, and
      glutathione conjugation to yield polar metabolites that are substrates for
      transporters. These events suggest that transcription factor(s) controlling the
      upregulation of antioxidant proteins, Phase II xenobiotic-metabolizing enzymes,
      and Phase III transporters should affect arsenic-mediated oxidative stress and
      the steady-state level of arsenic in the cells. In this review, we summarize
      recent progress in arsenic toxicity in terms of disrupted signal transduction
      cascades, the transcription factors involved, and arsenic biotransformation,
      including a novel pathway.

PMID- 17002599
TI  - The obesity epidemic: current and future pharmacological treatments.
AB  - The unabated rise in the prevalence of obesity is a challenge for global health
      care systems. Efforts to reverse this trend by dietary or behavioral counseling
      have not been successful, which has stimulated efforts to find a role for
      pharmacotherapy. Currently only a small number of antiobesity drugs are approved
      for long-term use and only a few compounds are in clinical development. Despite
      recent progress in the understanding of the regulation of energy balance, drug
      discovery has been less productive than expected. In the present review, the
      clinically available antiobesity agents are discussed. Examples of drug
      candidates that are currently in development are given and the possible future
      range of antiobesity agents is illustrated by the targets being addressed in drug
      discovery. Finally, the efficacy of antiobesity agents and their value in the
      treatment of obesity are assessed in comparison with other therapeutic
      approaches, such as surgery and changes in lifestyle.

PMID- 17002597
TI  - Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular
      disease.
AB  - First identified as a powerful vasoconstrictor, endothelin has an extremely
      diverse set of actions that influence homeostatic mechanisms throughout the body.
      Two receptor subtypes, ET(A) and ET(B), which usually have opposing actions,
      mediate the actions of endothelin. ET(A) receptors function to promote
      vasoconstriction, growth, and inflammation, whereas ET(B) receptors produce
      vasodilation, increases in sodium excretion, and inhibit growth and inflammation.
      Potent and selective receptor antagonists have been developed and have shown
      promising results in the treatment of cardiovascular diseases such as pulmonary
      arterial hypertension, acute and chronic heart failure, hypertension, renal
      failure, and atherosclerosis. However, results are often contradictory and
      complicated because of the tissue-specific vasoconstrictor actions of ET(B)
      receptors and the fact that endothelin is an autocrine and paracrine factor whose
      activity is difficult to measure in vivo. Considerable questions remain regarding
      whether ET(A)-selective or nonselective ET(A)/ET(B) receptor antagonists would be
      useful in a range of clinical settings.

PMID- 17002600
TI  - Generation and release of nitrotyrosine O-sulfate by HepG2 human hepatoma cells
      upon SIN-1 stimulation: identification of SULT1A3 as the enzyme responsible.
AB  - In addition to serving as a biomarker of oxidative/nitrative stress, elevated
      levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis.
      Whether the body is equipped with mechanisms for protecting against the
      potentially harmful nitrotyrosine remains unknown. The present study was designed
      to investigate the possibility that sulfation serves as a pathway for the
      metabolism/regulation of nitrotyrosine. Using metabolic labelling, nitrotyrosine
      O-[35S]sulfate was found to be produced and released into the medium of HepG2
      human hepatoma cells labelled with [35S]sulfate in the presence of nitrotyrosine.
      To identify the enzyme(s) responsible for nitrotyrosine sulfation, a systematic
      study of all eleven known human cytosolic SULTs (sulfotransferases) was
      performed. Of the 11 enzymes tested, only SULT1A3 displayed sulfating activity
      toward nitrotyrosine. The pH-dependence and kinetic constants of SULT1A3 with
      nitrotyrosine or dopamine as substrate were determined. To examine whether the
      sulfation of nitrotyrosine occurs in the context of cellular physiology, HepG2
      cells labelled with [35S]sulfate were treated with SIN-1 (morpholinosydnonimine),
      a peroxynitrite generator. Increments of nitrotyrosine O-[35S]sulfate were
      detected in the medium of HepG2 cells treated with higher concentrations of SIN
      1. To gain insight into the physiological relevance of nitrotyrosine sulfation, a
      time-course study was performed using [3H]tyrosine-labelled HepG2 cells treated
      with SIN-1. The findings confirm that the bulk of free [3H]nitrotyrosine inside
      the cells was present in the unconjugated form. The proportion of sulfated
      [3H]nitrotyrosine increased dramatically in the medium over time, implying that
      sulfation may play a significant role in the metabolism of free nitrotyrosine.

PMID- 17002601
TI  - Glutamine gluconeogenesis in the small intestine of 72 h-fasted adult rats is
      undetectable.
AB  - Recent reports have indicated that 48-72 h of fasting, Type 1 diabetes and high
      protein feeding induce gluconeogenesis in the small intestine of adult rats in
      vivo. Since this would (i) represent a dramatic revision of the prevailing view
      that only the liver and the kidneys are gluconeogenic and (ii) have major
      consequences in the metabolism, nutrition and diabetes fields, we have thoroughly
      re-examined this question in the situation reported to induce the highest rate of
      gluconeogenesis. For this, metabolically viable small intestinal segments from 72
      h-fasted adult rats were incubated with [3-13C]glutamine as substrate. After
      incubation, substrate utilization and product accumulation were measured by
      enzymatic and NMR spectroscopic methods. Although the segments utilized
      [13C]glutamine at high rates and accumulated 13C-labelled products linearly for
      30 min in vitro, no substantial glucose synthesis could be detected. This was not
      due to the re-utilization of [13C]glucose initially synthesized from
      [13C]glutamine. Arteriovenous metabolite concentration difference measurements
      across the portal vein-drained viscera of 72 h-fasted Wistar and Sprague-Dawley
      rats clearly indicated that glutamine, the main if not the only gluconeogenic
      precursor taken up, could not give rise to detectable glucose production in vivo.
      Therefore we challenge the view that the small intestine of the adult rat is a
      gluconeogenic organ.

PMID- 17002603
TI  - Illegal use of nitrofurans in food animals: Contribution to human salmonellosis?
AB  - Recent observations in Portugal of a remarkable incidence (65%) of Salmonella
      isolates from several sources (predominantly human and poultry) with decreased
      susceptibility to nitrofurantoin (MIC > or =64 mg/L), mostly comprising serogroup
      D isolates of Salmonella Enteritidis belonging to different phage types, suggest
      that illegal use of nitrofurans, especially in the poultry industry, might have
      contributed to the selection and prevalence of S. Enteritidis in food animals,
      and consequently to human salmonellosis in Portugal. Indiscriminate use of
      nitrofurans might also be implicated in the emergence of two multiresistant
      Salmonella Typhimurium clones disseminated throughout the country.

PMID- 17002602
TI  - Mutagenesis and mechanistic study of a glycoside hydrolase family 54 alpha-L
      arabinofuranosidase from Trichoderma koningii.
AB  - A GH (glycoside hydrolase) family 54 alpha-L-arabinofuranosidase from Trichoderma
      koningii G-39 (termed Abf) was successfully expressed in Pichia pastoris and
      purified to near homogeneity by cation-exchange chromatography. To determine the
      amino acid residues essential for the catalytic activity of Abf, extensive
      mutagenesis of 24 conserved glutamate and aspartate residues was performed. Among
      the mutants, D221N, E223Q and D299N were found to decrease catalytic activity
      significantly. The kcat values of the D221N and D299N mutants were 7000- and 1300
      fold lower respectively, than that of the wild-type Abf. E223Q was nearly
      inactive. These results are consistent with observations obtained from the
      Aspergillus kawachii alpha-L-arabinofuranosidase three-dimensional structure.
      This structure indicates that Asp221 of T. koningii Abf is significant for
      substrate binding and that Glu223 as well as Asp299 function as a nucleophile and
      a general acid/base catalyst for the enzymatic reaction respectively. The
      catalytic mechanism of wild-type Abf was further investigated by NMR spectroscopy
      and kinetic analysis. The results showed that Abf is a retaining enzyme. It
      catalyses the hydrolysis of various substrates via the formation of a common
      intermediate that is probably an arabinosyl-enzyme intermediate. A two-step,
      double-displacement mechanism involving first the formation, and then the
      breakdown, of an arabinosyl-enzyme intermediate was proposed. Based on the kcat
      values of a series of aryl-alpha-L-arabinofuranosides catalytically hydrolysed by
      wild-type Abf, a relatively small Bronsted constant, beta(lg)=-0.18, was
      obtained, suggesting that the rate-limiting step of the enzymatic reaction is the
      dearabinosylation step. Further kinetic studies with the D299G mutant revealed
      that the catalytic activity of this mutant depended largely on the pK(a) values
      (>6) of leaving phenols, with beta(lg)=-1.3, indicating that the rate-limiting
      step of the reaction becomes the arabinosylation step. This kinetic outcome
      supports the idea that Asp299 is the general acid/base residue. The pH activity
      profile of D299N provided further evidence strengthening this suggestion.

PMID- 17002604
TI  - Herpes simplex virus type 1 and respiratory disease in critically-ill patients:
      Real pathogen or innocent bystander?
AB  - Herpes simplex virus type 1 (HSV-1) has been associated with pulmonary disease,
      mostly in severely immunocompromised patients. After reactivation and shedding in
      the oropharynx, the virus may reach the lower respiratory tract by aspiration or
      by contiguous spread. HSV-1 can be detected in clinical specimens by virus
      culture or quantitatively by nucleic acid amplification techniques. With these
      techniques, HSV-1 is often detected in the respiratory secretions of critically
      ill patients. However, a clear diagnosis of HSV-1 pneumonia is difficult to
      establish because clinical criteria, radiological features and laboratory
      findings all lack specificity. Lower respiratory tract HSV-1 infections have not
      been associated with specific risk-factors. There is also an absence of
      consistent data concerning the effect of antiviral treatment on the outcome of
      critically-ill patients. Further studies are needed to better define the
      pathogenic role of HSV-1 in the lower respiratory tract of these patients, to
      improve the diagnosis, and, especially, to assess the need for antiviral
      treatment in the individual patient.

PMID- 17002605
TI  - Post-operative aspergillosis.
AB  - While invasive aspergillosis occurs typically in severely immunocompromised
      patients, cases of surgical site infection have been reported in immunocompetent
      individuals. The Medline, LILACS and EMBASE databases were searched for
      descriptions of cases of post-operative aspergillosis, and references from
      relevant articles and conference abstracts were reviewed. More than 500 cases of
      post-operative aspergillosis were found. Cardiac surgery (n = 188),
      ophthalmological surgery (n > 90) and dental surgery (n > 100) were associated
      with the majority of cases. Other cases involved wound infections (n = 22),
      bronchial infections (n = 30), mediastinitis (n = 11), pleural aspergillosis (n =
      1), infections following orthopaedic surgery (n = 42), vascular prosthetic
      surgery (n = 22), breast surgery (n = 5), abdominal surgery (n = 10) and
      neurosurgery (n = 25). In most patients, the source was presumed to be airborne
      infection during the surgical procedure. Prevention of these infections requires
      special care of the ventilation system in the operating room. Successful
      treatment requires rapid diagnosis, surgical debridement and antifungal therapy,
      often with voriconazole. In order to improve the outcome, better diagnostic
      methods are needed, particularly for cases of endocarditis and aortitis.

PMID- 17002606
TI  - Relationships among genotypes, virulence and clinical forms of Sporothrix
      schenckii infection.
AB  - This study explored the relationships among genotypes, virulence and clinical
      forms of Sporothrix schenckii. Genomic DNA from isolates of S. schenckii,
      collected from different clinical forms of sporotrichosis, was amplified by
      randomly amplified polymorphic DNA (RAPD). Suspensions of different isolates of
      S. schenckii were inoculated into healthy BALB/c mice to compare their virulence,
      and the numbers and distribution of spores were determined by histological
      analysis. RAPD analysis indicated that the isolates from different clinical forms
      of sporotrichosis belonged to different genotypes. The mice inoculated with
      isolates from disseminated sporotrichosis showed an earlier onset of illness and
      more severe lesions than those inoculated with isolates from lymphocutaneous
      sporotrichosis, which, in turn, showed an earlier onset of illness and more
      severe lesions than those inoculated with isolates from fixed cutaneous
      sporotrichosis. Healthy BALB/c mice injected with isolates from disseminated
      sporotrichosis died within 10 days, whereas isolates from lymphocutaneous
      sporotrichosis and fixed cutaneous sporotrichosis failed to cause death.
      Histologically, mice inoculated with isolates from disseminated sporotrichosis
      had more spores than those inoculated with isolates from lymphocutaneous
      sporotrichosis and fixed cutaneous sporotrichosis. Thus, different genotypes may
      be associated closely with the virulence of different clinical forms of S.
      schenckii infection.

PMID- 17002607
TI  - Improvement in immune parameters and human immunodeficiency virus-1 viral
      response in individuals treated with 16alpha-bromoepiandrosterone (HE2000).
AB  - A randomised, double-blind, placebo-controlled study examined the safety,
      tolerance, immunological effect and anti-human immunodeficiency virus (HIV)
      activity of sub-cutaneously administered HE2000 (16alpha-bromoepiandrosterone) as
      monotherapy in treatment-naive patients with HIV-1. Twenty-four patients received
      five sequential daily doses of 50 or 100 mg of HE2000 or placebo every 6 weeks
      for up to three courses, and were followed thereafter for 3 months. HE2000 was
      safe, with transient injection site reactions being the main side-effect.
      Peripheral blood samples, collected serially, were analysed for changes in immune
      cell phenotypes. Significant increases were observed in the numbers of
      circulating dendritic cells, early activated (CD69+ CD25-) CD8 T-cells and T-NK
      cells after administration of 50-mg doses of HE2000 (p < 0.05). Gene expression
      in peripheral blood mononuclear cells was analysed by real-time RT-PCR. Before
      treatment, HIV-1-infected patients had significantly elevated transcripts for a
      number of inflammatory mediators (p < 0.012). After 50 mg or 100 mg HE2000, but
      not after placebo, there were significant sustained decreases in IL-1beta, TNF
      alpha, IL-6 and Cox-2 transcripts (p < 0.05). There were no significant
      differences in CD4 cell numbers, although patients receiving 50-mg doses
      demonstrated a significant decrease in viral load (- 0.6 log; p < 0.01). Anti-HIV
      1 T-cell responses were analysed serially using GAG-peptides to stimulate
      cytoplasmic IFN-gamma responses. After three courses, the 50-mg dose group
      demonstrated a significant increase in CD8 T-cell response against two distinct
      GAG peptide pools (p < 0.03). These findings suggest that immune-based therapies
      may be able to impact viral load by decreasing inflammation and/or stimulating
      CD8 T-cells.

PMID- 17002608
TI  - Detection of human coronavirus NL63, human metapneumovirus and respiratory
      syncytial virus in children with respiratory tract infections in south-west
      Sweden.
AB  - Two recently detected viruses, human metapneumovirus (hMPV) and coronavirus NL63
      (HCoV-NL63), have been associated with acute respiratory tract infections,
      particularly in young children. This study investigated the frequency of hMPV and
      HCoV-NL63 infections in Swedish children by screening 221 nasopharyngeal
      aspirates, collected between November 2003 and May 2005, from 212 children
      attending the paediatric department of a county hospital in Sweden or submitted
      from local general practitioners. The samples were originally submitted to be
      tested for respiratory syncytial virus (RSV), and were examined retrospectively
      for hMPV and HCoV-NL63 by RT-PCR. Of the 212 patients, 101 were positive for RSV
      (48%), 22 (10%) were positive for hMPV, and 12 (6%) were positive for HCoV-NL63.
      The frequency of HCoV-NL63 infection increased from 1% in 2003-2004 to 10% in
      2004-2005. Sequence analysis of parts of the coronavirus genomes showed
      considerable similarity to the HCoV-NL63 prototype sequence. The study
      demonstrated that HCoV-NL63 and hMPV occur in south-west Sweden with essentially
      the same frequency, seasonal distribution and clinical characteristics as have
      been reported in other countries.

PMID- 17002609
TI  - Prognostic factors for early clinical failure in patients with severe community
      acquired pneumonia.
AB  - For patients with community-acquired pneumonia (CAP), clinical response during
      the first days of treatment is predictive of clinical outcome. As risk
      assessments can improve the efficiency of pneumonia management, a prospective
      cohort study to assess clinical, biochemical and microbiological predictors of
      early clinical failure was conducted in patients with severe CAP (pneumonia
      severity index score of >90 or according to the American Thoracic Society
      definition). Failure was assessed at day 3 and was defined as death, a need for
      mechanical ventilation, respiratory rate >25/min, PaO2 <55 mm Hg, oxygen
      saturation <90%, haemodynamic instability, temperature >38 degrees C or
      confusion. Of 260 patients, 80 (31%) had early clinical failure, associated
      mainly with a respiratory rate >25/minute (n = 34), oxygen saturation <90% (n =
      28) and confusion (n = 20). In multivariate logistic regression analysis, failure
      was associated independently with altered mental state (OR 3.19, 95% CI 1.75
      5.80), arterial PaH <7.35 mm Hg (OR 4.29, 95% CI 1.53-12.05) and PaO2 <60 mm Hg
      (OR 1.75, 95% CI 0.97-3.15). A history of heart failure was associated inversely
      with clinical failure (OR 0.30, 95% CI 0.10-0.96). Patients who failed to respond
      had a higher 28-day mortality rate and a longer hospital stay. It was concluded
      that routine clinical and biochemical information can be used to predict early
      clinical failure in patients with severe CAP.

PMID- 17002610
TI  - Pathophysiology of in-vitro induced filaments, spheroplasts and rod-shaped
      bacteria in neutropenic mice.
AB  - This study compared the in-vitro properties and in-vivo effects of Escherichia
      coli filaments, spheroplasts and normal cells in a murine thigh infection model.
      E. coli was exposed to ceftazidime, meropenem or saline to obtain filaments,
      spheroplasts or normal bacilli, which were then injected into neutropenic mice.
      After 24 h, morphology, CFUs, local and circulating endotoxin levels, cytokine
      levels and mortality were recorded, and correlations between bacterial and host
      parameters of infection were investigated. Filaments and spheroplasts contained
      more endotoxin/CFU than controls. Histological studies showed that
      morphologically altered bacteria changed into rod-shaped cells in the absence of
      antibiotics. Bacterial spread to the liver was significantly higher in mice
      challenged with rod-shaped cells, compared with antibiotic-exposed bacteria (p
      0.007). Muscle endotoxin levels correlated significantly with circulating
      interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, and both pro
      inflammatory cytokines were correlated significantly (p 0.011). Despite a
      tendency toward higher local and systemic concentrations of endotoxin in the
      filament group, inflammatory responses and survival did not differ between
      groups. It was concluded that morphologically altered bacteria contain more
      endotoxin and can regain a rod shape after withdrawal of antibiotics, while non
      antibiotic-exposed bacteria show greater spread to the liver. There was a clear
      intra-individual relationship between local endotoxin, systemic endotoxin, TNF
      alpha and IL-6 production, but these parameters did not differ among groups.

PMID- 17002611
TI  - Comparison of the performance of serological kits for Helicobacter pylori
      infection with European and Asian study populations.
AB  - Most commercial kits for the detection of Helicobacter pylori were developed and
      validated with Western populations, and some have been found to perform less well
      with Asian populations. This study compared the performances of three serological
      kits with Swedish and Vietnamese peptic ulcer patients and asymptomatic
      individuals. The Pyloriset EIA-GIII and HM-CAP ELISA kits indicated that Asian
      populations had lower antibody titres to H. pylori than European populations.
      Despite the difference, the Pyloriset EIA-GIII kit performed well with Vietnamese
      peptic ulcer patients and population controls. The HM-CAP ELISA kit had a
      significantly lower performance with Asian populations that could not be improved
      by adjustments to the cut-off level. The Helicoblot 2.1 immunoblot kit performed
      equally well with Vietnamese and Swedish populations, although the response rate
      to the 35-kDa band was significantly lower with Vietnamese individuals.

PMID- 17002612
TI  - Visual detection of IS6110 of Mycobacterium tuberculosis in sputum samples using
      a test based on colloidal gold and latex beads.
AB  - The IS6110 sequence was detected visually in sputum samples of tuberculosis
      patients using a bi-probe system. One of the probes was an oligonucleotide
      conjugated to colloidal gold particles, complementary to one end of the target
      strand. The other probe was an oligonucleotide conjugated to latex beads
      complementary to the other end of the target strand. In a reaction mix, these two
      probes bind to the target strand, and the latex beads are then separated by
      filtration. Bound latex beads have gold colloid particles at the other end of the
      target strand. These gold colloid particles were made visible to the naked eye by
      silver autometallography on the 'invisible' colloidal gold particles. The lower
      detection limit was 50 ng of genomic DNA of Mycobacterium tuberculosis. This new
      test, together with conventional PCR, was performed on DNA extracted from sputum
      samples of suspected tuberculosis patients. The new test was simple to perform,
      the results were visible to the naked eye, and the test was highly specific, as
      even single point mutations in the target strand sequence could be
      differentiated. The test could be useful in field-level laboratories because it
      requires no sophisticated equipment.

PMID- 17002613
TI  - Multilocus sequence typing and analysis of putative virulence factors in
      vancomycin-resistant and vancomycin-sensitive Enterococcus faecium isolates from
      Brazil.
AB  - Enterococci are leading causes of hospital-acquired infections that are often
      difficult to treat because of high-level aminoglycoside and glycopeptide
      resistance. Vancomycin-resistant enterococci are a global problem, and have been
      isolated with increasing frequency in hospitals in Brazil. The objective of this
      study was to determine the genetic relatedness of vancomycin-resistant
      Enterococcus faecium (VREFM) and vancomycin-sensitive E. faecium (VSEFM) isolated
      from human infections and faecal sources in Brazil, and to compare these isolates
      with those from domesticated animals. Isolates (n = 56) were classified by
      multilocus sequence typing (MLST) and assessed for putative virulence traits. The
      acm gene was detected in 98% of all isolates. The 56 isolates studied comprised
      26 different MLST types. VSEFM isolates from the faeces of pigs were found to be
      distinct from all human isolates characterised previously by MLST, and were
      assigned new sequence type (ST) numbers. VREFM isolates were represented by four
      different STs (ST-114, ST-17, ST-281, ST-50). Among the 26 STs identified in this
      study, eBURST detected three groups of STs with related allelic profiles, and 19
      unrelated STs. Among E. faecium isolates from Brazil, the esp gene was restricted
      to vancomycin-resistant isolates. Furthermore, isolates classified as ST-17 by
      MLST, an epidemic strain type isolated internationally with the purK-1 gene, were
      found among VREFM isolates from Brazil that also harboured the esp and hyl genes.

PMID- 17002614
TI  - Antimicrobial resistance among faecal enterococci from healthy individuals in
      Portugal.
AB  - Analysis of 247 faecal enterococcal isolates from 99 healthy Portuguese
      individuals during 2001 revealed the presence of enterococci resistant to
      vancomycin (5%) and highly resistant to streptomycin (52%), kanamycin (40%) or
      gentamicin (11%). Most isolates were also resistant to tetracycline,
      erythromycin, ciprofloxacin and quinupristin-dalfopristin. The vanA (two Tn1546
      types), vanC1, erm(B), aac(6')-aph(2'')-Ia, aph(3')-IIIa, vat(E) and vat(D) genes
      were detected. Enterococcus faecalis and Enterococcus faecium isolates with high
      level resistance to gentamicin were related to Portuguese poultry isolates
      described previously. E. faecium isolates that were highly resistant to
      vancomycin or gentamicin harboured different housekeeping purK alleles associated
      previously with different hosts.

PMID- 17002615
TI  - Genotypic diversity and antibiotic susceptibility of Acinetobacter baumannii
      isolates in a Bulgarian hospital.
AB  - A set of 18 Acinetobacter baumannii isolates, collected prospectively in a
      Bulgarian hospital during episodes of increased A. baumannii occurrence during
      2000-2002, was investigated for genotypic diversity and antibiotic
      susceptibility. Four genotypes were identified by amplified fragment length
      polymorphism genomic fingerprinting, one of which (type 1) accounted for 13
      isolates, indicating that a specific strain was predominant. The single isolate
      allocated to type 2 was identified to European clone I. All isolates were
      resistant to multiple antibiotics, but most retained susceptibility to tobramycin
      and colistin, and all except one were susceptible to imipenem.

PMID- 17002616
TI  - Nosocomial spread of OXA-58-positive carbapenem-resistant Acinetobacter baumannii
      isolates in a paediatric hospital in Greece.
AB  - Twelve non-repetitive Acinetobacter baumannii isolates producing the carbapenem
      hydrolysing oxacillinase OXA-58 were recovered from patients in the same
      paediatric hospital in Athens, Greece, between November 2003 and May 2005. All
      isolates were clonally related, but the bla(OXA-58) gene was not always plasmid
      located and there were variations in the DNA sequences surrounding the OXA-58
      gene in different isolates. This study emphasises the importance of the bla(OXA
      58) carbapenemase gene in conferring carbapenem resistance among A. baumannii
      isolates in Greece.

PMID- 17002617
TI  - Comparison of secular trends in pneumococcal serotypes causing invasive disease
      in Denver, Colorado (1971-2004) and serotype coverage by marketed pneumococcal
      vaccines.
AB  - Invasive pneumococcal isolates from three hospitals in Denver, CO, USA were
      serotyped between 1971 and 2004. Serotype 14 was most common (13.2%), and other
      prevalent serotypes (3, 4, 6, 9 and 19) together accounted for 44.1% of the
      isolates. All prevalent serotypes and 91.3% of the total isolates were covered by
      pneumococcal polysaccharide vaccine, while 79.1% of prevalent serotypes and 56.7%
      of total isolates were covered by pneumococcal conjugate vaccine. Serotypes 6, 9
      and 14 were more common in the final decade than in the first decade studied
      (37.3% vs. 20.2%), whereas serotypes 3 and 23 were more common in the first
      decade (18.5% vs. 11.0%).

PMID- 17002618
TI  - A bioinformatics pipeline for high-throughput microbial multilocus sequence
      typing (MLST) analyses.
AB  - Multilocus sequence typing (MLST) analysis for semi-routine applications is
      hindered by the downstream, manually intensive steps of processing the raw
      sequence data files. This report describes the development of an MLST pipeline
      that automates DNA sequence editing and analysis in order to significantly reduce
      the time required for processing data. Validation using a pneumococcal dataset
      revealed complete agreement between the results generated by manual and automated
      workflows. The MLST pipeline was developed for both double-strand and single
      strand sequencing.

PMID- 17002619
TI  - Transfusion medicine illustrated. Marrow emboli in acute chest syndrome: artifact
      or etiology?

PMID- 17002620
TI  - Randomized clinical trials in thrombotic thrombocytopenic purpura: where do we go
      from here?

PMID- 17002621
TI  - Lessons and opportunities from epidemiologic and molecular investigations of
      infected blood donors.

PMID- 17002622
TI  - Iron depletion by whole-blood donation harms menstruating females: the current
      whole-blood-collection paradigm needs to be changed.

PMID- 17002623
TI  - The production of red blood cell alloantibodies in mice transfused with blood
      from transgenic Fyb-expressing mice.
AB  - BACKGROUND: A murine model would be useful to identify which immune mechanisms
      could be manipulated to treat or prevent red blood cell (RBC) alloimmunization in
      patients who become sensitized to multiple or widely expressed antigens. STUDY
      DESIGN AND METHODS: Transgenic mice (B6CBAF1/J-Tg-Fy(b)) expressing the human
      Fy(b) antigen of the Duffy (Fy) blood group were donors. Recipient B6CBA-F1 mice
      received four weekly intravenous (IV) transfusions: either 0.3 mL of washed buffy
      coat-depleted RBCs or 0.3 mL of RBCs with spleen cells. Titers of immunoglobulin
      M (IgM) and immunoglobulin G (IgG) were measured in recipient serum samples by
      flow cytometry with RBCs from donor mice as target cells. Recipient serum samples
      were also tested against human RBCs of various Fy phenotypes. Additionally, RBC
      survival studies were performed in alloimmunized mice utilizing biotin-labeled
      Fy(b) transgenic mouse RBCs. RESULTS: B6CBA-F1 mice receiving washed buffy coat
      depleted RBCs first made IgM, followed by IgG alloantibodies to transgenic mouse
      Fy(b)-positive RBCs. Recipients of Fy(b)-positive RBCs mixed with spleen cells
      also produced IgM and IgG alloantibodies, but at a slower rate than recipients of
      washed buffy coat-depleted RBCs. Serum samples showed specificity for Fy3, Fy(b),
      and Fy6. Decreased survival of transfused RBCs was evident at 24 hours after
      transfusion. CONCLUSIONS: It is possible to elicit the formation of anti-Fy
      alloantibodies by IV transfusion in mice that lack Fy antigens. The transfusion
      of RBCs alone was adequate to stimulate alloantibody production in B6CBA-F1
      recipient mice. The survival of transfused Fy(b)-positive RBCs is diminished in
      sensitized mice. This model will be useful in further studies of RBC
      alloimmunization.

PMID- 17002624
TI  - Molecular basis of the LOCR (Rh55) antigen.
AB  - BACKGROUND: In 1994 during the investigation of a case of hemolytic disease of
      the newborn, a new low-incidence red cell (RBC) antigen, LOCR, was described.
      Although the presence of LOCR was associated with altered expression of Rh
      antigens, its formal assignment to the Rh blood group system did not occur until
      haplotype and linkage analysis conducted in 2003 provided the necessary proof.
      The current study was undertaken in an attempt to define the underlying RH
      mutation in LOCR+ individuals. STUDY DESIGN AND METHODS: Genomic DNA from five
      unrelated LOCR+ individuals and three Rh-matched control individuals was
      amplified by polymerase chain reaction with intronic primers flanking all 10
      exons of RH. Amplified products were separated on 1 percent agarose gels and
      isolated for DNA sequence analysis in both the forward and the reverse
      directions. RESULTS: DNA sequence analysis of the three LOCR+ D- individuals
      revealed a single heterozygous 286G>A nucleotide substitution resulting in a
      predicted Gly>Ser substitution at amino acid 96. DNA sequence analysis from the
      two LOCR+ D+ individuals revealed the identical mutation, as well as all of the
      changes associated with the common RHD gene. CONCLUSIONS: Based on our results, a
      Gly96Ser substitution in the Rhce polypeptide defines the low-incidence RBC
      antigen known as LOCR. This same amino acid change has previously been shown to
      be involved in the Rh:-26 phenotype, which suggests that LOCR and Rh26 are
      antithetical. Serologic investigations with various Rh:-26 cells and serum
      samples, however, reveal that only some c+ Rh:-26 phenotypes are LOCR+.

PMID- 17002625
TI  - A randomized, controlled Phase III trial of therapeutic plasma exchange with
      fresh-frozen plasma (FFP) prepared with amotosalen and ultraviolet A light
      compared to untreated FFP in thrombotic thrombocytopenic purpura.
AB  - BACKGROUND: Photochemical treatment of fresh-frozen plasma (FFP) with amotosalen
      and ultraviolet (UV) A light (PCT FFP) results in inactivation of a broad
      spectrum of pathogens while retaining coagulation factor activity, antithrombotic
      proteins, and von Willebrand factor-cleaving protease (VWF-CP) activity. STUDY
      DESIGN AND METHODS: A randomized, controlled, double-blind Phase III trial was
      conducted with PCT FFP or control FFP for therapeutic plasma exchange (TPE) in
      patients with thrombotic thrombocytopenic purpura (TTP). Owing to the rarity of
      this diagnosis, the trial was not powered to demonstrate small differences
      between treatment groups. Patients were treated with study FFP for a maximum of
      35 days until remission was achieved (for a maximum of 30 daily study TPEs with
      no remission) plus an additional 5 days after remission. RESULTS: Among the 35
      patients treated, the primary endpoint, remission within 30 days, was achieved by
      14 of 17 (82%) PCT patients and 16 of 18 (89%) control patients (p = 0.658) The
      90 percent confidence interval for treatment difference in remission rate for
      test - control was (-0.291 to 0.163). Time to remission, relapse rates, time to
      relapse, total volume and number of FFP units exchanged, and number of study TPEs
      were not significantly different between groups. Improvement in VWF-CP and
      inhibitors was similar for both groups. The overall safety profile of PCT FFP was
      similar to control FFP. No antibodies to amotosalen neoantigens were detected.
      CONCLUSION: The comparable results between treatment groups observed from this
      small trial suggest that TPE with PCT FFP was safe and effective for treatment of
      TTP.

PMID- 17002626
TI  - Acquired lysosomal storage caused by frequent plasmapheresis procedures with
      hydroxyethyl starch.
AB  - BACKGROUND: Hydroxyethyl starch (HES) solutions have largely replaced
      conventional plasma expanders such as human albumin and colloidal fluids. Only a
      few side effects have been reported and mainly concern pruritus or blood
      coagulation disorders. Excessive HES exposure can result in diffuse tissue
      storage and accumulation with foamy appearing macrophages which produce the
      enzyme chitotriosidase (CT). In case of massive tissue storage, this enzyme
      activity can reach levels comparable to those of Gaucher disease. STUDY DESIGN
      AND METHODS: In this single-center retrospective analysis of 11 consecutive
      patients receiving large amounts of HES for chronic plasmapheresis, plasma CT
      activity was investigated. Five patients receiving chronic intermittent
      plasmapheresis with conventional plasma expanders served as controls. Plasma CT
      activity was measured and plotted against creatinine clearance. Where available,
      marrow aspirate was analyzed with light microscopy to detect foamy macrophages.
      One patient developed a lysosomal storage disease and was examined extensively.
      RESULTS: Conventional plasma expanders did not alter plasma CT activity. In
      patients with impaired renal function, frequent plasma replacement with HES
      resulted in an increase in plasma CT activity. In the patient with the acquired
      lysosomal storage disease, massive tissue infiltration with activated foamy
      macrophages was observed. The phagocytic capacity in this patient, however, did
      not seem to be altered. CONCLUSION: Patients with impaired renal function
      receiving large amounts of HES exhibit an increase in plasma CT activity. Because
      excessive HES exposure can result in an acquired lysosomal storage disease, this
      should be avoided in chronic plasmapheresis procedures.

PMID- 17002627
TI  - Effects of storage time of red blood cell transfusions on the prognosis of
      coronary artery bypass graft patients.
AB  - BACKGROUND: In different centers for cardiothoracic surgery throughout the world,
      different policies are followed concerning the maximum storage time of to-be
      transfused red blood cells (RBCs). The aim in this study was to investigate the
      possible role of the storage time of RBC transfusions on the outcome of coronary
      artery bypass graft (CABG) surgery patients. STUDY DESIGN AND METHODS: In a
      single-center study, all patients who had undergone CABG surgery in the period
      1993 until 1999 were identified. Only those patients who had received standard,
      allogeneic, buffy coat-depleted, unfiltered RBCs in saline-adenine-glucose
      mannitol were entered in the analyses (n = 2732). Endpoints were 30-day survival,
      hospital stay, and intensive care unit (ICU) stay. Storage time of the
      perioperative RBC transfusions was analyzed in the following four ways: 1) mean
      storage time of all perioperative RBC transfusions; 2) storage time of the
      youngest RBC transfusion; 3) storage time of the oldest RBC transfusion; and 4)
      comparing outcome in patients receiving only RBCs with a storage time below the
      median storage of 18 days with patients receiving only RBCs with a storage time
      above the median. RESULTS: The univariate analyses showed a strong correlation
      between storage time and the endpoints survival and ICU stay, but also a
      correlation with an established risk factor such as the number of transfusions.
      The multivariate analyses showed no independent effect of storage time on
      survival or ICU stay. CONCLUSION: In these analyses, pertaining to 2732 CABG
      patients, no justification could be found for use of a particular maximum storage
      time for RBC transfusions in patients undergoing CABG surgery.

PMID- 17002628
TI  - Diversity and origin of hepatitis C virus infection among unpaid blood donors in
      the Netherlands.
AB  - BACKGROUND: To improve transfusion policy and to increase understanding of the
      spread of hepatitis C virus (HCV) in the general population, HCV infections among
      voluntary Dutch blood donors were examined with molecular epidemiologic
      techniques. STUDY DESIGN AND METHODS: During 6 years, 1997 through 2002,
      confirmed anti-HCV-positive donors were interviewed on HCV-associated risk
      behavior with a standardized questionnaire. Additionally, HCV isolates were
      genotyped, partially sequenced, and compared to sequences obtained from Dutch
      injecting drug users (IDUs). RESULTS: HCV prevalence and incidence rates among
      Dutch donors were extremely low; the residual risk of transmitting HCV was
      calculated to be 1 in 30 million donations. Former IDUs (21%), transfusion
      recipients (30%), and immigrants (>12%) were identified as major HCV risk groups.
      Cryptogenic transmission caused 18 percent of infections among new donors and all
      infections among repeat donors. Compared to IDUs, genotype distribution among
      donors was highly diverse; major subtypes were 3a (27%), 1a (24%), 1b (24%), 2a/b
      (10%), and 4 (9%). Half of the donors were infected with IDU-related subtypes 1a
      and 3a, whereas subtype 1b mainly spread via blood transfusion and various other
      nosocomial modes of transmission in the past. HCV infections acquired in endemic
      countries could be clearly identified based on genotype. CONCLUSION: Different
      modes of transmission are linked to infections with certain HCV subtypes,
      suggesting separate HCV epidemics, but spillover between different risk groups
      underlines the value of molecular epidemiologic techniques to gain insight into
      the origin and dynamics of HCV infections on a population level.

PMID- 17002629
TI  - Surveillance of risk profiles among new and repeat blood donors with transfusion
      transmissible infections from 1995 through 2003 in the Netherlands.
AB  - BACKGROUND: To evaluate the effectiveness of blood donor selection, this study
      reports risk profiles of donors with transfusion-transmissible infections as
      obtained by ongoing surveillance, 1995 through 2003, in the Netherlands. STUDY
      DESIGN AND METHODS: A surveillance program was installed to monitor risk profiles
      among new and repeat donors infected with human immunodeficiency virus (HIV),
      hepatitis C virus (HCV), hepatitis B virus (HBV), or human T-lymphotropic virus
      (HTLV), or positive for the presence of syphilis antibodies. At posttest
      counseling, a physician interviewed donors to clarify possible sources of
      infection. RESULTS: A total of 167 repeat donors and 404 new donors were
      interviewed: 33 with HIV, 123 with HCV, 279 with HBV, 21 with HTLV, and 112 with
      syphilis antibodies. Most HBV, HCV, and HTLV infections were among new donors
      (80, 85, and 67%), whereas most HIV infections were among repeat donors (79%).
      Nearly 25 percent of the donors did not report factors at screening that would
      have deferred them from donating blood. At posttest interviews, new donors with
      HCV often reported injecting drug use (19%). Repeat donors with HIV often
      reported male-to-male sex (8/26, 31%). CONCLUSION: A significant level of
      deferrable behavioral risks was found among donors with confirmed transfusion
      transmissible infections that persist despite current donor selection. Reporting
      such behavior at initial donor selection would have eliminated a substantial part
      of the infections found. This study argues against relaxing the existing donor
      deferral of persons practicing male-to-male sex, given their significant
      proportion of HIV infections among repeat donors. Systematic surveillance of risk
      factors among infected blood donors provides ongoing information about the
      effectivity of donor selection and is recommended to evaluate and optimize blood
      policies.

PMID- 17002630
TI  - Evaluation of a prototype Trypanosoma cruzi antibody assay with recombinant
      antigens on a fully automated chemiluminescence analyzer for blood donor
      screening.
AB  - BACKGROUND: Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite
      that can be transmitted by transfusion. The diagnosis of chronic T. cruzi
      infection is generally made by detecting specific antibodies that bind to
      parasite antigens. The aim of this study was to assess the sensitivity and
      specificity of a new serologic assay for antibodies to T. cruzi on a fully
      automated analyzer (PRISM, Abbott Laboratories). STUDY DESIGN AND METHODS: A
      prototype chemiluminescent immunoassay based on chimeric recombinant antigens and
      run on the automated PRISM system was developed for detecting antibodies to T.
      cruzi in human serum and plasma. Assay specificity was evaluated by testing
      samples from random blood donors and from a diverse group of specimens from
      persons with diseases or conditions often associated with false-positive
      reactions in T. cruzi assays. Sensitivity was determined by testing 377
      geographically diverse T. cruzi antibody-positive specimens. RESULTS: Six of 7911
      samples (0.08%) from random donors were repeatedly reactive in the prototype
      PRISM Chagas assay. One of these was reactive in three other tests, including the
      radioimmune precipitation assay and was presumed to be a true positive. Hence,
      the specificity was 99.94 percent (7905/7910) in the negative donor group
      studied. All 377 T. cruzi antibody-positive specimens were positive in the
      prototype assay and thus the sensitivity was 100 percent. CONCLUSION: The results
      obtained to date, in terms of sensitivity as well as specificity, strongly
      suggest that the PRISM Chagas assay should function well as a tool for screening
      blood for serologic evidence of T. cruzi infection.

PMID- 17002631
TI  - Safety and donor acceptance of an abbreviated donor history questionnaire.
AB  - BACKGROUND: Surveys have shown donor dissatisfaction with the duration of the
      donation process and repetitive questioning. An abbreviated donor history
      questionnaire (AQ) may improve satisfaction, but must be safe. STUDY DESIGN AND
      METHODS: An FDA-approved 34-question AQ was implemented in 2003. Travel,
      medication, and health history questions were decreased by 18. Donors were
      eligible for AQ if they had successfully completed three donor suitability
      assessments on the full-length questionnaire (FQ), including one in the prior 6
      months. Data were analyzed from more than 50,000 donations during each of three
      20-day periods over the first year of progressive implementation of the AQ. We
      evaluated the performance of the AQ by comparing donor deferrals for medical
      history (MHD), physical examination findings (PED), and reactive screening and/or
      confirmatory tests (RSCT) for viral markers among AQ-ineligible and AQ-eligible
      donors and separately among AQ-eligible donors who received AQ or FQ. RESULTS:
      Approximately one-third of presenting donors were AQ-eligible. Use of AQ
      progressed from 48 percent in October 2003 to 76 percent in November 2004. AQ
      eligible donors had lower rates of MHD, PED, and RSCT than donors ineligible for
      AQ (p < 0.05). Among donors eligible for the AQ, those who received the FQ had
      slightly more MHD and PED than those who received the AQ (p < 0.05), but there
      was no difference in RSCT. A postdonation survey indicated significantly
      increased satisfaction and intent to donate among donors who received the AQ.
      CONCLUSIONS: In frequent repeat donors, use of an AQ led to increased donor
      satisfaction and no significant medical concerns about donor or recipient safety.

PMID- 17002632
TI  - Latency-associated human cytomegalovirus glycoprotein N genotypes in monocytes
      from healthy blood donors.
AB  - BACKGROUND: The beta-herpesvirus human cytomegalovirus (HCMV) infects a variety
      of cell types and maintains a lifelong relationship with its host by way of a
      latent infection in circulating monocytes, myeloid precursor cells, and the
      hematopoietic progenitor population. Viral strain heterogeneity, shown by gene
      polymorphisms, has been implicated in the majority of HCMV biologic behaviors.
      HCMV UL73 encodes the polymorphic envelope glycoprotein N (gN), which shows seven
      genotypes (gN-1, gN-2, gN-3a, gN-3b, gN-4a, gN-4b, and gN-4c). STUDY DESIGN AND
      METHODS: Monocyte subfractions from 64 HCMV-seropositive healthy blood donors
      were collected to analyze gN genotypes distribution in the few cells harboring
      the latent viral genome. Different experimental approaches to extract viral
      genomes from the monocyte population and amplify UL73 (polymerase chain reaction
      touchdown and nested) for subsequent genotyping were tested and compared with
      diagnostic gold standard. gN genotype distribution in monocytes from
      immunocompetent healthy carriers was compared with previously reported data
      obtained from patient populations with acute HCMV infections. RESULTS: The
      efficiency of UL73 amplification from monocytes of healthy seropositive blood
      donors was approximately 39 percent, one of the highest reported to date. The
      leading gN genotype was gN-1 (87%), whereas the gN-4 variant was poorly
      represented (13%). The comparison of gN genotypic frequencies in the
      immunocompetent healthy population with immunocompromised patients is discussed.
      CONCLUSIONS: This work further supports the idea that strain-specific features
      could determine the cell tropism and influence the onset of latency.

PMID- 17002633
TI  - Viability and function of 8-day-stored apheresis platelets.
AB  - BACKGROUND: Methods of bacterial detection and pathogen inactivation of platelets
      (PLTs) may allow extended storage of PLTs as long as PLT quality is maintained.
      STUDY DESIGN AND METHODS: Twenty normal volunteers had their PLTs collected with
      an apheresis machine (Haemonetics Corp.). A variety of in vitro PLT function and
      metabolic assays were performed both on Day 0 and after 8 days of storage. On Day
      8, a small blood sample was drawn from each donor to obtain fresh PLTs. The fresh
      and stored autologous PLTs were labeled with either (51)Cr or (111)In, and the
      radiolabeled PLTs were transfused. Posttransfusion serial blood samples were
      drawn to determine the relative posttransfusion recoveries and survivals of the
      fresh versus the stored PLTs. RESULTS: Although the in vitro assays showed some
      differences between the two trial sites, the results were generally within the
      ranges expected for fresh and stored PLTs. Overall, PLT recoveries averaged 66 +/
      16 percent versus 53 +/- 20 percent and survivals averaged 8.5 +/- 1.6 days
      versus 5.6 +/- 1.6 days, respectively, for fresh compared to 8-day-stored PLTs.
      There were no significant differences in the in vivo PLT data between the trial
      sites or based on the radiolabel used for the measurements. CONCLUSION: After 8
      days of storage, the in vivo posttransfusion recovery and survival of autologous
      Haemonetics apheresis PLTs meet the proposed standards for poststorage PLT
      quality.

PMID- 17002634
TI  - Evaluation of inactivation methods for severe acute respiratory syndrome
      coronavirus in noncellular blood products.
AB  - BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV) has been
      detected in the blood of infected individuals, which may have the potential to
      contaminate donated blood and plasma-derived products in the event of a future
      outbreak. Effective methods for inactivating the SARS-CoV in protein solutions
      are described in this report. STUDY DESIGN AND METHODS: Heat, ultraviolet (UV)
      irradiation, octanoic acid, and solvent/detergent (S/D) methods were tested
      individually for their ability to inactivate SARS-CoV in protein solutions
      appropriately mimicking blood-derived products. Treated samples were tested for
      inactivation in a tissue culture growth assay. RESULTS: Viral inactivation by
      heat treatment at 60 degrees C required 15 to 30 minutes to inactivate the SARS
      CoV. UVC efficiently inactivated SARS-CoV in 40 minutes, whereas UVA required the
      addition of psoralen to enhance inactivation of the virus. The presence of bovine
      serum albumin limited the ability of UVC and UVA to inactivate SARS-CoV and
      octanoic acid treatment does not reduce the infectivity of SARS-CoV-spiked
      protein solutions. S/D treatment required 2, 4, and up to 24 hours for Triton X
      100, Tween 80, and sodium cholate inactivation, respectively. CONCLUSION: Heat,
      UVC irradiation, and S/D treatments effectively inactivate SARS-CoV, whereas
      octanoic acid treatment is insufficient for inactivation of the virus.

PMID- 17002635
TI  - Viability of red cells prepared with S-303 pathogen inactivation treatment.
AB  - BACKGROUND: A nucleic acid-targeted pathogen inactivation process with S-303 was
      developed to treat red blood cells (RBCs). STUDY DESIGN AND METHODS: Three
      studies in healthy subjects investigated posttransfusion recovery, life span, and
      immunogenic potential of autologous RBCs treated with S-303 and stored for 35
      days. A two-arm trial in 42 subjects (1A) examined recovery of 35-day-old S-303
      RBCs after a single transfusion. A one-arm study (1B) measured recovery and
      immune response in 28 subjects after multiple transfusions of S-303 RBCs. A
      randomized, crossover study (1C) in 29 subjects compared recovery and life span
      of 35-day-old S-303 RBCs and conventional RBCs. RESULTS: In Studies 1A and 1B,
      mean recovery of S-303 RBCs ranged from 78.7 to 84.4 percent. In Phase 1C, the
      mean 24-hour posttransfusion recoveries of S-303 and untreated RBCs were 81.7 +/-
      6.3 and 84.5 +/- 6.2 percent (p = 0.05). The median life spans (t(1/2)) of S-303
      and control RBCs were identical (37.4 days, p = 0.98). No antibodies to S-303
      RBCs were detected. CONCLUSION: The mean 24-hour recovery of 35-day-old S-303
      RBCs was less than untreated RBCs, but greater than 75 percent. RBCs treated with
      S-303 and stored for 35 days exhibited median life span not different from that
      of conventional RBCs.

PMID- 17002636
TI  - Two-year experience with aerobic culturing of apheresis and whole blood-derived
      platelets.
AB  - BACKGROUND: Throughout its system of regional centers, Blood Systems implemented
      culture based bacterial testing with a standardized protocol for both apheresis
      and whole blood-derived platelets (PLTs). STUDY DESIGN AND METHODS: After a 24
      hour hold, 4 mL of PLT product was inoculated into an aerobic bottle (BacT/ALERT,
      bioMerieux). Cultures were incubated for 24 hours before routine product release
      to prevent distribution of infected products while minimizing consignee
      notification, product retrievals, and hospital PLT inventory problems. Initial
      positives were further tested (and bacteria identified) by performing cultures
      from the original component and subcultures from the BacT/ALERT bottle. Results
      were categorized according to AABB recommended definitions with minor
      modifications. RESULTS: The rate of true-positive detections from culturing
      122,971 apheresis PLTs was 0.017 percent (95% confidence interval [CI], 0.011%
      0.026%). All true-positive microorganisms were Gram-positive with a predominance
      of coagulase-negative Staphylococcus and Bacillus species. Twenty of the 21 true
      positive samples (95%) were detected by 24 hours but only 14 (68%) were detected
      by 18 hours. The false-positive rate due to contamination was 0.1 percent with
      the majority of isolates being skin or environmental organisms. Results did not
      differ significantly for whole blood-derived versus apheresis PLTs. CONCLUSION:
      These data corroborate the fact that the rate of detection of truly contaminated
      PLT apheresis products in the United States is approximately 1 in 5000 (0.02%);
      this is lower than the 0.03 to 0.05 percent rates that were generally quoted in
      the literature before the implementation of prospective bacterial culturing
      programs.

PMID- 17002637
TI  - Recombinant human granulocyte-colony-stimulating factor-mobilized and apheresis
      collected endothelial progenitor cells: a novel blood cell component for
      therapeutic vasculogenesis.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) have been identified among
      hematopoietic tissue-derived progenitor cells that are mobilized into the
      peripheral blood (PB) as a result of tissue injury. It therefore seems likely
      that circulating EPCs have therapeutic potential by aiding in the
      neovascularization of ischemic tissue. This study provides clinical data on the
      availability of circulating EPCs at steady state and after recombinant human
      granulocyte-colony-stimulating factor (rHuG-CSF) mobilization and their
      collection by leukapheresis. STUDY DESIGN AND METHODS: Eight healthy donors
      underwent rHuG-CSF treatment over 4 days, followed by leukapheresis. Blood
      samples taken before rHuG-CSF treatment and before apheresis as well as apheresis
      collected samples were analyzed by flow cytometry and by real time reverse
      transcription-polymerase chain reaction for cells expressing EPC-specific surface
      markers and tissue markers, respectively, and for EPC colony-forming cells.
      RESULTS: The median PB concentration of CD34+133+ vascular endothelial growth
      factor receptor-2 (VEGFR-2)-+ EPCs increased 8-fold from steady state to
      mobilized, and the concentration of CD34+133-VEGFR-2+ EPCs increased by 10-fold.
      This mobilization pattern was similar to that of hematopoietic CD34+, CD133+, and
      CD34+117+ progenitor cells. The increase in the median circulating colony-forming
      unit EPC concentration was 10-fold over baseline. The median absolute number of
      CD34+133+VEGFR-2+ cells collected by large-volume leukapheresis was 0.8 x 10(6)
      per kg of body weight. In addition, a small subset of immature CD133+34- cells
      coexpressing VEGFR-2 was identified in mobilized PB and in the apheresis
      collection. EPC-specific cells contained in the apheresis product were also
      identified as expressing mRNA for the CD31 antigen, Tie-2, and VEGFR-2.
      CONCLUSION: Circulating EPCs represent a novel blood cell component that can be
      collected by apheresis in large quantities and can be used clinically, either
      unmanipulated or EPC-selected, for therapeutic vasculogenesis.

PMID- 17002638
TI  - Factors associated with parameters of engraftment potential of umbilical cord
      blood.
AB  - BACKGROUND: Umbilical cord blood (UCB) is an acceptable source of hematopoietic
      cells for transplantation with success being associated with the nucleated cell
      count (NCC), CD34+ cells, and colony-forming unit-granulocyte-macrophage (CFU-GM)
      content infused. A total of 1033 UCB samples with neonatal and paternal
      characteristics that might influence hematopoietic content were examined. STUDY
      DESIGN AND METHODS: UCB samples were screened, processed, and reevaluated for the
      above cell counts. These parameters of engraftment potential were analyzed for
      associations with neonatal and parental characteristics. RESULTS: Postprocessed
      NCCs (median, 6.53 x 10(8)+/- 2.80 x 10(8) SD; mean 7.30 x 10(8)), CD34+ counts
      (median, 2.02 x 10(6) +/- 2.20 x 10(6) SD; mean, 2.65 x 10(6); r = 0.66; p <
      0.001), and CFU-GM content (median, 2.65 x 10(5) +/- 3.16 x 10(5) SD; mean, 3.54
      x 10(5); r = 0.61; p < 0.001) all were strongly interrelated. Both initial volume
      (median, 77.5 +/- 26.2 mL SD; mean, 81.9 mL) and initial NCC (median, 9.75 x
      10(8) +/- 4.88 x 10(8) SD; mean, 10.9 x 10(8)) correlated well with postprocessed
      NCC (r = 0.60; r = 0.90; p < 0.01), CD34+ count (r = 0.40; r = 0.63; p < 0.01),
      and CFU-GM content (r = 0.38; r = 0.59; p < 0.01), with a stronger relationship
      seen with initial NCC. Infant birth weight (specifically, >3000 g), but not sex,
      gestational age, or cytomegalovirus status correlated strongly with collection
      volume and UCB cell counts. Units from minority volunteers contained relatively
      smaller volumes and hematopoietic content. CONCLUSION: UCB banks should emphasize
      selecting the heaviest infants and processing large-volume units with high NCCs
      to optimize hematopoietic potential. Minority recruitment should be encouraged
      with consideration given to inherent racial differences in cell counts. There
      does not appear to be a significant relationship between other neonatal and
      parental characteristics and that of engraftment potential.

PMID- 17002639
TI  - An association of soluble CD40 ligand (CD154) with adverse reactions to platelet
      transfusions.
AB  - BACKGROUND: Removal of stored supernatant abrogates most transfusion reactions to
      leukoreduced platelets (PLTs), suggesting that PLT-derived soluble mediators are
      involved. PLTs are the primary source of soluble CD40 ligand (sCD40L). Engagement
      of the receptor for CD40L induces synthesis of proinflammatory mediators
      including interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1 (MCP-1).
      STUDY DESIGN AND METHODS: Supernatants from poststorage leukoreduced PLT
      concentrates were assayed for white cell- (IL-6, IL-8, MCP-1) and PLT-derived
      (sCD40L, RANTES) inflammatory mediators. These levels were correlated with
      clinical outcomes. RESULTS: Of 534 transfusions, there were 12 reported (2.2%)
      and 2 unreported reactions (0.4%)--10 febrile and 4 allergic. Transfusions with
      reactions had significantly higher levels of IL-6 (2.3-fold higher; p = 0.005),
      IL-8 (2.2-fold higher; p = 0.001), MCP-1 (2.6-fold higher; p = 0.002), and sCD40L
      (1.24-fold higher; p = 0.015), but not RANTES. (1.14-fold higher; p = 0.22). The
      vast majority (>93%) of patients transfused with mediator levels in the highest
      quintile had no reactions. When levels of all five mediators were summed, the
      reaction rates in the first through fifth quintiles increased from 1 to 7 percent
      (p = 0.027). All but one reaction occurred in patients with hematologic
      malignancies (13 reactions/380 transfusions; 3.4%; p = 0.04 vs. other diagnoses).
      CONCLUSIONS: These are the first data demonstrating that a PLT-derived mediator,
      sCD40L, is associated with adverse transfusion events. Existing clinical factors,
      for example, inflammation or leukopenia, may influence whether infused mediators
      cause reactions.

PMID- 17002640
TI  - Accuracy of hepatitis C virus core antigen testing in pools among seroconverters.
AB  - BACKGROUND: Screening blood units for hepatitis C virus (HCV) with nucleic acid
      testing (NAT) reduces the risk associated with the long "window period" (8-9
      weeks) after HCV infection. The feasibility of adding the HCV core antigen assay
      in pools to the existing anti-HCV individual screening was examined as an
      alternative of NAT, for early detection of HCV. STUDY DESIGN AND METHODS:
      Eighteen HCV seroconversion panels were tested for HCV antibodies, HCV antigen,
      and HCV RNA. Each sample was tested for HCV antigen individually and in pools of
      3, 6, and 12. Statistical analyses included estimation of time until detection of
      the first positive HCV antigen bleed in each pool size, with a locally weighted
      regression (LOWESS) model. Sensitivity was calculated compared to NAT. RESULTS:
      Detection of HCV antigen in individual samples and in pools of 3 and 6
      significantly preceded the detection of antibodies by 63, 53, and 46 days,
      respectively. Although the sensitivity of the HCV antigen test decreased with the
      increase in pool size, the estimated overall sensitivity of the "two-stage"
      antigen and antibody screening (where NAT of individual samples was the gold
      standard) was not significantly different between individual and the different
      pool sizes. CONCLUSION: Screening for HCV antigen in pools of 6 can be considered
      an efficient and easier-to-implement alternative to the costly NAT for
      identifying blood donors in the seroconversion period. It may offer a cost
      effective approach in resource utilization in poor countries, that, after the
      implementation of HCV antibody testing, want to further improve blood safety.

PMID- 17002641
TI  - Quantification of hepatitis B virus genomes and infectivity in human serum
      samples.
AB  - BACKGROUND: Hepatitis B virus (HBV) infections are still a major health issue,
      with approximately 350 million people chronically infected with HBV worldwide.
      Information about the minimum copy number of HBV genomes required for infection
      would be useful as a reference for drug and vaccine development; for monitoring
      HBV patients during treatment; for screening of blood, organ, and tissue donors;
      and for regulating nucleic acid amplification assays for HBV. STUDY DESIGN AND
      METHODS: Serum samples from chronic carriers (hepatitis B surface antigen
      positive and antibody to HBV core antigen-positive) of the three most common
      subtypes of HBV were studied; their infectivity titers had been evaluated
      previously in chimpanzees. The genotypes of the HBV samples were determined by
      DNA sequences and type-specific amino acids of the S gene of HBV. Copy numbers of
      HBV DNA were quantified by real-time TaqMan polymerase chain reaction (PCR) and
      by nested PCR applied to limiting dilutions. The copy number determined for each
      inoculum was compared with previously defined chimpanzee infectivity titers.
      RESULTS: The genotypes of the HBV adw, ayw, and adr inocula were A, D, and C,
      respectively. The concentration of HBV DNA was determined to be 5.4 x 10(9), 2.5
      x 10(9), and 3.1 x 10(8) genome equivalents (geq) per mL for serum samples
      containing the adw, ayw, and adr, respectively. The chimpanzee infectivity titers
      per milliliter of these initial HBV-containing serum samples were previously
      determined to be 10(7.5) for adw, 10(7.5) for ayw (MS-2 strain), and 10(8) for
      adr. CONCLUSION: The minimal copy number of HBV DNA in chronic carriers of HBV
      that can infect the chimpanzee model was estimated to be from 3 to 169 geq based
      upon the three well-characterized inocula.

PMID- 17002642
TI  - ABO blood group determines plasma von Willebrand factor levels: a biologic
      function after all?
AB  - For many years, an association between ABO histo-blood group and risk of
      thrombosis has been recognized. Blood group non-O (A, B, and AB) individuals have
      consistently been found to demonstrate increased incidence of both arterial and
      venous thrombotic disease, compared to group O individuals. This increased risk
      is attributable to the fact that ABO blood group influences plasma levels of a
      coagulation glycoprotein named von Willebrand factor (VWF). VWF levels are 25
      percent higher in non-O compared to group O individuals. The mechanism by which
      ABO group determines plasma VWF levels has not been determined. ABO(H)
      carbohydrate antigenic determinants, however, are expressed on the N-linked
      glycan chains of circulating plasma VWF. This review will focus on the
      carbohydrate structures of VWF and recent studies suggesting that subtle
      variations in these structures (particularly differences in ABO blood group
      antigen expression) may have clinically significant effects on VWF proteolysis
      and clearance.

PMID- 17002644
TI  - Performance of serological assays used to test blood from recent smallpox
      vaccinees.

PMID- 17002645
TI  - A total solution for zero-risk, zero-time-lag, and zero-wastage blood transfusion
      service.

PMID- 17002647
TI  - An alternative strategy for collecting granulocytes without sedimenting agents.

PMID- 17002650
TI  - Characterization of rat thrombin-activatable fibrinolysis inhibitor (TAFI)--a
      comparative study assessing the biological equivalence of rat, murine and human
      TAFI.
AB  - BACKGROUND AND OBJECTIVES: Activated thrombin-activatable fibrinolysis inhibitor
      (TAFIa) attenuates fibrinolysis. Although rat models to study the role of TAFI
      are available, the biochemical properties of rat TAFI are not well investigated
      and immunologic tools are lacking. Therefore, we have characterized recombinant
      rat TAFI-6His and compared its properties with those of human TAFI as well as of
      murine TAFI-V5-6His. METHODS AND RESULTS: TAFI from all three species is
      activatable by the thrombin-thrombomodulin complex, generating a highly unstable
      protein (TAFIa). Half-lives at 37 degrees C are 8.5+/-0.6 min, 3.4+/-0.4 min and
      2.2+/-0.2 min for human, rat and murine TAFIa, respectively. The 50% clot lysis
      times are 6+/-1 min for TAFI-depleted rat plasma and 137+/-34 min, 62+/-9 min and
      50+/-8 min when TAFI-depleted rat plasma is supplemented with 0.02 U of human,
      rat or murine TAFIa, respectively, which correlates with their half-lives. Upon
      incubation with the thrombin-thrombomodulin complex, the 36-kDa fragment of rat
      and murine TAFI is not cleaved into 25-kDa and 11-kDa fragments. Upon incubation
      of rat TAFI and murine TAFI with plasmin, a 32-kDa fragment is formed due to
      cleavage at Arg147, in contrast to the formation of a 36-kDa fragment for human
      TAFI. Concomitantly, activity levels upon plasmin incubation are drastically
      reduced for rat and murine TAFI. CONCLUSIONS: Recombinant human, rat and murine
      TAFI have similar but not identical biochemical characteristics, suggesting a
      similar role during fibrinolysis in vivo.

PMID- 17002651
TI  - What causes the enhancement of activity of factor VIIa by tissue factor?

PMID- 17002652
TI  - Low ankle-brachial index predicts an adverse 1-year outcome after acute coronary
      and cerebrovascular events.
AB  - BACKGROUND: Low ankle-brachial Index (ABI) identifies patients with symptomatic
      and asymptomatic peripheral arterial disease. The aim of this study was to
      correlate ABI value (normal or low) with 1-year clinical outcome in patients
      hospitalized for acute coronary syndromes or cerebrovascular diseases (CVD).
      METHODS: ABI was measured in consecutive patients hospitalized because of acute
      myocardial infarction, unstable angina, stroke or transient ischemic attack
      (TIA). An ABI lower than or equal to 0.90 was considered abnormal. The primary
      outcome of the study was the composite of non-fatal acute myocardial infarction,
      non-fatal ischemic stroke, and death from any cause during the year following the
      index event. RESULTS: An abnormal ABI was found in 27.2% of 1003 patients with
      acute coronary syndromes, and in 33.5% of 755 patients with acute CVD. After a
      median follow-up of 372 days, the frequency of the primary outcome was 10.8%
      (57/526) in patients with abnormal ABI and 5.9% (73/1232) in patients with normal
      ABI [odds ratio (OR) 1.96; 95% CI 1.36-2.81]. Death was more common in patients
      with abnormal ABI (OR 2.05; 95% CI 1.31-3.22). Cardiovascular mortality accounted
      for 81.7% of overall mortality. ABI was predictive of adverse outcome after
      adjustment for vascular risk factors in the logistic regression analysis (OR
      1.93; 95% CI 1.24-3.01). The predictive value of ABI was mainly accounted for by
      patients hospitalized for acute coronary syndromes (adverse outcome: 12.8% in
      patients with abnormal ABI and 5.9% in patients with normal ABI, OR 2.35; 95% CI
      1.47-3.76). CONCLUSIONS: An abnormal ABI can be found in one-third of patients
      hospitalized for acute coronary or cerebrovascular events and is a predictor of
      an adverse 1-year outcome.

PMID- 17002653
TI  - Efficacy and safety of adeno-associated viral vectors based on serotype 8 and 9
      vs. lentiviral vectors for hemophilia B gene therapy.
AB  - BACKGROUND: Adeno-associated viral (AAV) and lentiviral vectors are promising
      vectors for gene therapy for hemophilia because they are devoid of viral genes
      and have the potential for long-term gene expression. OBJECTIVES: To compare the
      performance of different AAV serotypes (AAV8 and AAV9) vs. lentiviral vectors
      expressing factor (F) IX. METHODS AND RESULTS: AAV-based and lentiviral vectors
      were generated that express FIX from the same hepatocyte-specific expression
      cassette. AAV9 transduced the liver as efficiently as AAV8 and resulted in supra
      physiological FIX levels (3000-6000% of normal) stably correcting the bleeding
      diathesis. Surprisingly, AAV9 resulted in unprecedented and widespread cardiac
      gene transfer, which was more efficient than with AAV8. AAV8 and AAV9 were not
      associated with any proinflammatory cytokine induction, in accordance with their
      minimal interactions with innate immune effectors. In contrast, lentiviral
      transduction resulted in modest and stable FIX levels near the therapeutic
      threshold (1%) and triggered a rapid self-limiting proinflammatory response
      (interleukin-6), which probably reflected their ability to efficiently interact
      with the innate immune system. CONCLUSIONS: AAV8 and 9 result in significantly
      higher FIX expression levels and have a reduced proinflammatory risk in
      comparison with lentiviral vectors. The unexpected cardiotropic properties of
      AAV9 have implications for gene therapy for heart disease.

PMID- 17002654
TI  - Associations of plasma fibrinogen and factor VII clotting activity with coronary
      heart disease and stroke: prospective cohort study from the screening phase of
      the Thrombosis Prevention Trial.
AB  - BACKGROUND: As with 'conventional' risk factors such as cholesterol and smoking,
      there is a need for large, long-term prospective studies on hemostatic factors.
      OBJECTIVES: To investigate the prospective relationship of fibrinogen and factor
      VII clotting activity (FVIIc) with risk of coronary heart disease (CHD) and
      stroke in a study with a large number of outcomes over a period of 15 years.
      PATIENTS/METHODS: A cohort of 22 715 men aged 45-69 years was screened for
      participation in the Thrombosis Prevention Trial. Men were followed up for fatal
      and non-fatal CHD and stroke events. There were 1515 CHD events (933 CHD deaths)
      and 391 strokes (180 stroke deaths). Hazard ratios (HRs) and 95% confidence
      intervals are expressed per standardized increase in log fibrinogen and log
      FVIIc, adjusting for age, trial treatment group, conventional CHD risk factors
      and regression dilution bias. RESULTS: Hazard ratios for fibrinogen were 1.52
      (1.37-1.70) for all CHD events, and 1.36 (1.09-1.69) for all strokes. Exclusion
      of events within the first 10 years showed a persistent association between CHD
      and fibrinogen, with an adjusted HR of 1.93 (1.42-2.64). The HRs for FVIIc,
      adjusting for age and trial treatment, were 1.07 (1.01-1.12) for all CHD events
      and 1.07 (0.97-1.20) for all strokes, and the fully adjusted HRs were,
      respectively, 0.97 (0.84-1.05) and 1.07 (0.85-1.33). CONCLUSIONS: The persisting
      association between fibrinogen and CHD beyond 10 years may imply a causal effect.
      There is a small effect of FVIIc on CHD, after adjustment for age and trial
      treatment, but no association independent of other risk factors.

PMID- 17002655
TI  - Who is at risk for occult cancer after venous thromboembolism?

PMID- 17002656
TI  - Allosteric disulfide bonds in thrombosis and thrombolysis.
AB  - Allosteric disulfide bonds control protein function by mediating conformational
      change when they undergo reduction or oxidation. The known allosteric disulfide
      bonds are characterized by a particular bond geometry, the -RHStaple. A number of
      thrombosis and thrombolysis proteins contain one or more disulfide bonds of this
      type. Tissue factor (TF) was the first hemostasis protein shown to be controlled
      by an allosteric disulfide bond, the Cys186-Cys209 bond in the membrane-proximal
      fibronectin type III domain. TF exists in three forms on the cell surface: a
      cryptic form that is inert, a coagulant form that rapidly binds factor VIIa to
      initiate coagulation, and a signaling form that binds FVIIa and cleaves protease
      activated receptor 2, which functions in inflammation, tumor progression and
      angiogenesis. Reduction and oxidation of the Cys186-Cys209 disulfide bond is
      central to the transition between the three forms of TF. The redox state of the
      bond appears to be controlled by protein disulfide isomerase and NO.
      Plasmin(ogen), vitronectin, glycoprotein 1balpha, integrin beta(3) and
      thrombomodulin also contain -RHStaple disulfides, and there is circumstantial
      evidence that the function of these proteins may involve cleavage/formation of
      these disulfide bonds.

PMID- 17002657
TI  - A Bbeta 14 Arg --> Cys fibrinogen variant in a patient with thrombotic
      complications (fibrinogen St-Germain III).

PMID- 17002658
TI  - Severe prothrombin deficiency caused by prothrombin-Edmonton (R-4Q) combined with
      a previously undetected deletion.
AB  - BACKGROUND: During infancy, a male patient experienced several life-threatening
      bleeding episodes. Standard coagulation tests revealed that the patient's plasma
      prothrombin activity was 8%, while his father's and mother's levels were 74% and
      62%, respectively. OBJECTIVES: A molecular genetic approach was used to determine
      the molecular basis of prothrombin deficiency within the family. PATIENT/METHODS:
      Prothrombin genomic DNA fragments were amplified by using the polymerase chain
      reaction (PCR). In addition, liver cDNA fragments were amplified from the patient
      by using reverse transcription (RT) and PCR. The nucleotide sequences of the DNA
      fragments were determined. RESULTS: A novel, heterozygous point mutation (g.1755
      G > A, named prothrombin-Edmonton) was detected in the patient and his mother,
      resulting in the mutation of Arg-4 in the prothrombin propeptide to Gln (R-4Q).
      RT-PCR analysis of the patient's liver sample demonstrated the presence of two
      mRNA transcripts that differed by the presence or absence of exon 11. Real-time
      PCR analysis on genomic DNA and cDNA confirmed a deletion (g.10435_10809del) in
      the paternal allele. CONCLUSIONS: The patient has a maternally-inherited point
      mutation (R-4Q) and a paternally-inherited deletion. By analogy with the
      previously reported factor IX San Dimas, the R-4Q mutation probably causes under
      carboxylation of prothrombin and poor cleavage of the propeptide in the
      hepatocyte. The deletion probably results in a polypeptide that lacks 50 amino
      acids from the protease domain; this is likely to impair folding, secretion,
      stability and/or activity of the truncated prothrombin. The two mutations combine
      to give the prothrombin deficiency observed in the patient.

PMID- 17002659
TI  - Incidence of inhibitors in a cohort of 838 males with hemophilia A previously
      treated with factor VIII concentrates.
AB  - BACKGROUND: Development of an inhibitory antibody to factor VIII is currently the
      most serious complication of hemophilia A treatment. The rate of inhibitor
      development in those that have been previously treated with factor concentrates
      is poorly defined. Understanding the baseline rate of inhibitor development in
      the population of previously treated patients (PTPs) is important when evaluating
      the effect of exposure to new factor replacement products on inhibitor formation.
      OBJECTIVES: To determine the rate of inhibitor development in PTPs with
      hemophilia A. METHODS: A cohort of males with hemophilia A who had data collected
      on four or more occasions prior to 30 March 2003, as part of the Center for
      Disease Control and Prevention's Universal Data Collection Project, were eligible
      for inclusion in the cohort. Patients were included in the cohort if they had at
      least two Bethesda assay measurements and did not have an inhibitor prior to or
      at the start of the study period. The overall incidence rate was estimated as the
      number of verified incident inhibitor cases divided by the total follow-up time
      in years multiplied by 1000 (cases per 1000 person-years). RESULTS: A total of
      838 patients were included in the study. The overall incidence rate was
      calculated to be 2.14 cases per 1000 person years. All incident cases had more
      than 50 exposure days prior to inhibitor development. CONCLUSIONS: Given the low
      rate of inhibitor development in PTPs with hemophilia A, small, non-randomized
      studies are inadequate to determine the rate of inhibitor development after
      exposure to novel products. Ongoing, standardized, postmarketing surveillance is
      needed to determine if novel factor products pose an increased risk of inhibitor
      development.

PMID- 17002661
TI  - Evidence that pre-existent variability in platelet response to ADP accounts for
      'clopidogrel resistance'.
AB  - BACKGROUND: Clopidogrel is a widely used antithrombotic agent that inhibits the
      platelet P2Y(12) adenosine diphosphate (ADP) receptor. There is increasing
      interest in 'clopidogrel resistance'. OBJECTIVES: To determine whether
      'clopidogrel resistance' is accounted for by a pre-existent variability in
      platelet response to ADP. METHODS: Platelet response to 20 microm ADP was
      analyzed by four independent whole blood flow cytometric assays: platelet surface
      activated GPIIb-IIIa, platelet surface P-selectin, monocyte-platelet aggregates
      and neutrophil-platelet aggregates. In 25 consecutive, non-aspirin-treated
      healthy subjects, we studied platelet response before and after clopidogrel
      administration. In addition, we studied the platelet response in 613 consecutive
      aspirinated patients with or without coronary artery disease (CAD, as determined
      by angiography) who had or had not been treated with clopidogrel. In these
      patients, we tested for homogeneity of variance across all durations of
      clopidogrel exposure and severity of CAD by estimating the 'goodness of fit' of
      two independent models. RESULTS: In the healthy subjects, pre-clopidogrel
      response to ADP predicted post-clopidogrel response to ADP. In the patients,
      clopidogrel, as expected, inhibited the platelet response to ADP. However,
      irrespective of the duration of clopidogrel administration, the severity of CAD,
      and the dose of aspirin, clopidogrel did not increase the variance in the
      platelet response to ADP in any of the four assays of platelet response.
      CONCLUSIONS: These studies provide evidence that 'clopidogrel resistance' is
      accounted for by a pre-existent variability in platelet response to ADP and this
      variability is not increased by clopidogrel administration.

PMID- 17002660
TI  - Plasmodium falciparum-infected erythrocytes induce tissue factor expression in
      endothelial cells and support the assembly of multimolecular coagulation
      complexes.
AB  - BACKGROUND: Plasmodium falciparum malaria infects 300-500 million people every
      year, causing 1-2 million deaths annually. Evidence of a coagulation disorder,
      activation of endothelial cells (EC) and increase in inflammatory cytokines are
      often present in malaria. OBJECTIVES: We have asked whether interaction of
      parasitized red blood cells (pRBC) with EC induces tissue factor (TF) expression
      in vitro and in vivo. The role of phosphatidylserine-containing pRBC to support
      the assembly of blood coagulation complexes was also investigated. RESULTS: We
      demonstrate that mature forms of pRBC induce functional expression of TF by EC in
      vitro with productive assembly of the extrinsic Xnase complex and initiation of
      the coagulation cascade. Late-stage pRBC also support the prothrombinase and
      intrinsic Xnase complex formation in vitro, and may function as activated
      platelets in the amplification phase of the blood coagulation. Notably, post
      mortem brain sections obtained from P. falciparum-infected children who died from
      cerebral malaria and other causes display a consistent staining for TF in the EC.
      CONCLUSIONS: These findings place TF expression by endothelium and the
      amplification of the coagulation cascade by pRBC and/or activated platelets as
      potentially critical steps in the pathogenesis of malaria. Furthermore, it may
      allow investigators to test other therapeutic alternatives targeting TF or
      modulators of EC function in the treatment of malaria and/or its complications.

PMID- 17002662
TI  - Platelet function in patients with acute coronary syndrome (ACS) predicts
      recurrent ACS.
AB  - BACKGROUND: Platelet hyperfunction contributes to acute coronary syndromes (ACS).
      Thus, we hypothesized that platelet function under high shear stress predicts
      recurrent ACS during long-term follow-up of ACS patients. PATIENTS AND METHODS:
      Consecutive ACS patients (n = 208) were prospectively followed-up for an average
      of 28 months. Platelet function was measured with the platelet function analyzer
      (PFA-100; Dade Behring, Marburg, Germany) at baseline for collagen/adenosine
      diphosphate closure times (CADP-CT) and for collagen/epinephrine closure times
      (CEPI-CT) after infusion of a uniform dose of 250 mg aspirin. RESULTS: Of the
      conventional risk factors, only the prevalence of diabetes was higher in ACS
      patients with re-events. However, use of clopidogrel and use of beta blockers
      were also slightly lower in patients with re-events (P < 0.05). The unadjusted
      risk hazard ratio (HR) for re-events was 3.3 [95% confidence interval (95% CI):
      1.4-7.4; P = 0.005] in those patients with the shortest CADP-CT values (lowest
      quartile). Similarly, the risk was 2.0-fold higher (95% CI: 1.1-3.6; P = 0.02) in
      ACS patients with CEPI-CT < 300 s as compared with CEPI-CT >or = 300 s. Inclusion
      of diabetes, clopidogrel and beta blockers in a multivariate Cox regression model
      enhanced the predictive value of CEPI-CT (HR: 2.7). Inclusion of von Willebrand
      factor levels did not alter the HR for recurrent ACS (HR: 2.1; 95% CI: 1.1-5.2; P
      = 0.03) for CEPI-CT < 300 s, but reduced the HR for CADP-CT (HR: 2.8, 95% CI: 0.8
      9.8; P = 0.11). CONCLUSION: Shortened CT values reflect biologically relevant
      platelet hyperfunction in patients with ACS because they predict recurrent ACS.

PMID- 17002664
TI  - Abstracts of the 38th Annual Scientific Congress of the Royal Australian and New
      Zealand College of Ophthalmologists. November 4-8, 2006.

PMID- 17002663
TI  - Plasma hemostatic factors and endothelial markers in four racial/ethnic groups:
      the MESA study.
AB  - BACKGROUND: Hemostatic factors and endothelial markers may play some role in
      racial/ethnic differences in cardiovascular disease (CVD) rates. However, little
      information exists on hemostatic factors and endothelial markers across
      racial/ethnic groups. OBJECTIVES: To describe, in four American racial/ethnic
      groups (Caucasian, Black, Hispanic, and Chinese), mean levels of selected
      hemostatic factors and endothelial markers. PATIENTS AND METHODS: Multi-ethnic
      Study of Atherosclerosis baseline data were used (participant age: 45-84 years).
      Sex-specific analysis of covariance models, and t-tests for pairwise comparisons,
      were used to compare means of factors and markers. Adjustments were made for
      demographics and traditional CVD risk factors. Differences were significant at P
      < 0.05. RESULTS: Blacks had the highest levels of factor VIII, D-Dimer, plasmin
      antiplasmin (PAP), and von Willebrand factor, among the highest levels of
      fibrinogen and E-selectin (women only), but among the lowest levels of
      intercellular adhesion molecule 1 (ICAM-1), and, in men, the lowest levels of
      plasminogen activator inhibitor-1 (PAI-1). Whites and Hispanics tended to have
      intermediate levels of factors and markers, although they had the highest levels
      of ICAM-1, and Hispanics had the highest mean levels of fibrinogen and E-selectin
      (women only). Chinese participants had among the highest levels of PAI-1, but the
      lowest, or among the lowest, of all other factors and markers. No soluble
      thrombomodulin differences were observed. CONCLUSIONS: In this large cohort,
      hemostatic factor and endothelial marker mean levels varied by race/ethnicity,
      even after adjustment for traditional CVD risk factors.

PMID- 17002665
TI  - Computer simulations of transport through membranes: passive diffusion, pores,
      channels and transporters.
AB  - A key function of biological membranes is to provide mechanisms for the
      controlled transport of ions, nutrients, metabolites, peptides and proteins
      between a cell and its environment. We are using computer simulations to study
      several processes involved in transport. In model membranes, the distribution of
      small molecules can be accurately calculated; we are making progress towards
      understanding the factors that determine the partitioning behaviour in the
      inhomogeneous lipid environment, with implications for drug distribution,
      membrane protein folding and the energetics of voltage gating. Lipid bilayers can
      be simulated at a scale that is sufficiently large to study significant defects,
      such as those caused by electroporation. Computer simulations of complex membrane
      proteins, such as potassium channels and ATP-binding cassette (ABC) transporters,
      can give detailed information about the atomistic dynamics that form the basis of
      ion transport, selectivity, conformational change and the molecular mechanism of
      ATP-driven transport. This is illustrated in the present review with recent
      simulation studies of the voltage-gated potassium channel KvAP and the ABC
      transporter BtuCD.

PMID- 17002666
TI  - Role of hypothalamic alpha-adrenoceptor activity in fructose-induced
      hypertension.
AB  - The aim of the present study was to investigate the effects of the alpha2
      adrenoceptor antagonist yohimbine on blood pressure and heart rate (HR)
      regulation, as well as on adrenergic and serotoninergic neurotransmission, in
      fructose hypertensive (F) rats. The anterior hypothalamic area of control (C) and
      F rats was perfused with Ringer's solution containing 10 and 100 microg/mL
      yohimbine through a microdialysis concentric probe. The effects of yohimbine on
      mean arterial pressure (MAP) and HR, as well as on hypothalamic
      dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA)
      levels, were measured according to perfusion time. Although intrahypothalamic
      perfusion of yohimbine increased blood pressure in C rats (DeltaMAP 9 +/- 1 and
      11 +/- 2 mmHg for 10 and 100 microg/mL yohimbine, respectively; P < 0.05 vs
      Ringer's perfusion), the alpha-adrenoceptor antagonist did not modify MAP in F.
      Intrahypothalamic yohimbine had no effect on HR at either concentration tested.
      Intrahypothalamic perfusion of 10 and 100 microg/mL yohimbine increased DOPAC
      levels in C rats (135 +/- 6 and 130 +/- 5% of basal levels, respectively; both n
      = 6; P < 0.05 vs Ringer's perfusion), but not in F animals (115 +/- 6 and 102 +/-
      6% of basal levels, respectively; both n = 6). In both C and F rats, yohimbine
      administration induced an increase in 5-HIAA dialysate levels. The results of the
      present study support the notion that alpha2-adrenoceptor tone of the anterior
      hypothalamus of normotensive rats, which contributes to normal blood pressure
      regulation, is not involved in the control of HR in either normotensive C or
      hypertensive F rats. The absence of changes in MAP after yohimbine perfusion in F
      rats suggests that the alpha2-adrenoceptor tone could be decreased in this group
      of rats and that this may be responsible for the maintenance of hypertension in
      this model. Intrahypothalamic perfusion of yohimbine increased DOPAC in the
      dialysate only in C rats, suggesting changes in presynaptic alpha2-adrenoceptor
      activity in fructose-overloaded rats. Conversely, increased 5-HIAA levels did not
      differ between C and F groups.

PMID- 17002667
TI  - Paradoxically enhanced heart tolerance to ischaemia in type 1 diabetes and role
      of increased osmolarity.
AB  - There is considerable controversy regarding the tolerance of diabetic hearts to
      ischaemia and the underlying mechanisms responsible for the increased heart
      tolerance to ischamia remain uncertain. In the present study, we observed, in
      vitro, type 1 diabetic heart responses to ischaemia and reperfusion at different
      degrees of hyperglycaemia. In addition, the possible role of increased osmolarity
      in cardioprotection due to hyperglycaemia was evaluated. Hearts from 3 week
      streptozocin-induced diabetic rats were isolated and perfused in a Langendorff
      apparatus and subjected to 30 min ischaemia and 30 min reperfusion. Cardiac
      function and the electrocardiogram were recorded. Myocardial content of
      osmolarity associated heat shock protein (hsp) 90, heme oxygenase (HO)-1 and anti
      oxidant enzymes were determined in diabetic or hyperosmotic solution-perfused
      hearts using western blot. The hsp90 inhibitor 17-allylamino-17
      demethoxygeldanamycin (17-AAG; 2 x 10(-7) mol/L) or the nitric oxide synthase
      (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (1 x 10(-5) mol/L) was added
      to the perfusate to observe the effects of hsp90 inhibition and hsp90-associated
      endothelial NOS on ischaemic responses of diabetic hearts. Compared with normal
      control rats, diabetic hearts with severe hyperglycaemia (blood glucose > 20
      mmol/L) showed markedly improved postischaemic heart function with fewer
      reperfusion arrhythmias. Mild hyperglycaemia (< 12 mmol/L) exhibited no
      significant cardioprotection. Elevated expression of hsp90 accompanied the
      enhanced resistance to ischaemia in diabetic hearts, which was abrogated by 17
      AAG. In the presence of the NOS inhibitor, heart function was preserved, whereas
      reperfusion arrhythmias were increased in diabetes. Diabetic hearts also had
      markedly elevated HO-1 and catalase, with no significant change in superoxide
      dismutase. Hyperosmotic perfusion with glucose or mannitol also increased
      myocardial hsp90 and catalase. The present findings reveal that heart resistance
      to ischaemia is increased in short-term type 1 diabetes with severe
      hyperglycaemia. Elevated osmolarity caused by significant hyperglycaemia may
      contribute to the enhanced myocardial activity against oxidative injury during
      ischaemia and reperfusion.

PMID- 17002668
TI  - Extent of renal effect of cyclo-oxygenase-2-selective inhibitors is
      pharmacokinetic dependent.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) cause renal side-effects. In the
      present study, we tested the hypothesis that the extent of the renal effects of
      cyclo-oxygenase (COX)-2-selective NSAIDs is linked to their pharmacokinetics. A
      single oral dose of rofecoxib (10 mg/kg), celecoxib (40 mg/kg), meloxicam (3
      mg/kg) or placebo was administered to rats. Urinary excretion of electrolytes, a
      marker of renal effects, and plasma and kidney concentrations of NSAIDs were
      measured. Rofecoxib and celecoxib, but not meloxicam, significantly decreased
      urinary sodium and potassium excretion. There was a significant correlation
      between the area under the 24 h plasma concentration-time curve (AUC0-24) of
      rofecoxib and the change in sodium (r = -0.65; P < 0.02) and potassium (r = 
      0.82; P < 0.0006) excretion. The AUC0-24 of celecoxib was correlated with sodium
      (r = -0.80; P < 0.05) but not potassium excretion. The ratios of kidney to plasma
      drug concentrations were 1.72, 3.16 and 0.17 for rofecoxib, celecoxib and
      meloxicam, respectively. The renal effect of the COX-2-selective NSAIDs examined,
      marked by their ability to reduce the excretion of electrolytes, is influenced by
      systemic exposure to the drugs. The relatively higher distribution into the
      kidneys of rofecoxib and celecoxib compared with meloxicam suggests involvement
      of direct drug exposure in the kidneys in the adverse renal effect.

PMID- 17002669
TI  - Hepatoprotective and hypolipidaemic effects of glycoprotein isolated from
      Gardenia jasminoides ellis in mice.
AB  - The present study was performed to investigate the hepatoprotective and
      hypolipidaemic effects of a 27 kDa glycoprotein isolated from Gardenia
      jasminoides Ellis (GJE glycoprotein) in glucose/glucose oxidase (G/GO)-treated
      BNL CL.2 cells, as well as in CCl4, Triton WR-1339 and corn oil-treated mice. In
      G/GO-treated BNL CL.2 cells, the results showed that GJE glycoprotein has an
      inhibitory effect on G/GO-induced cytotoxicity and intracellular reactive oxygen
      species production. In addition, GJE glycoprotein has an anti-oxidant effect
      against the lipid peroxidation process in the Fe2+/ascorbic acid system. In CCl4
      (1.0 mL/kg)-treated mice, pretreatment with GJE glycoprotein (80 mg/kg) blocked
      lactate dehydrogenase release and the formation of thiobarbituric acid-reactive
      substances. In addition, in these mice GJE resulted in increased nitric oxide
      production and the activation of anti-oxidant enzymes, accompanied by the
      inhibition of the cytotoxic-related signals hepatic cytochrome c, nuclear factor
      kappaB and activator protein-1. In both Triton WR-1339 (400 mg/kg) and corn oil
      (1.0 g/kg)-treated mice, pretreatment with GJE glycoprotein (80 mg/kg) lowered
      the levels of plasma lipoproteins (triglyceride, total cholesterol and low
      density lipoprotein). On the basis of these results, we assume that GJE
      glycoprotein can ameliorate liver function, because it has hepatoprotective and
      hypolipidaemic activities.

PMID- 17002670
TI  - Docosahexaenoic acid-induced protective effect against impaired learning in
      amyloid beta-infused rats is associated with increased synaptosomal membrane
      fluidity.
AB  - In the present study, we investigated the relationship between the
      docosahexaenoic acid (DHA)-induced protection of learning deficit of amyloid
      beta(1-40)-infused Alzheimer's disease (AD) model rats and changes in
      synaptosomal plasma membrane fluidity of the cerebral cortex. Synaptosomal
      membrane lateral and rotational fluidity were measured using pyrene excimer
      spectroscopy and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene
      (DPH), respectively. Avoidance learning ability, as assessed by a two-way active
      avoidance paradigm, decreased significantly in the AD model rats. Pyrene
      determined annular/non-annular fluidity ratio and the DPH-determined bulk
      fluidity of the synaptosomal plasma membrane decreased in the amyloid beta(1-40)
      infused rats. Oral pre-administration of DHA (300 mg/kg per day for 12 weeks)
      significantly increased both lateral and rotational fluidity. The synaptosomal
      membrane DHA content increased and the cholesterol to phospholipid molar ratio
      and lipid peroxidation decreased. The annular to non-annular fluidity ratio of
      the synaptic plasma membrane was positively correlated with total avoidance
      learning. The present results indicate that DHA-induced alterations in synaptic
      plasma membrane fluidity may contribute to the synaptic plasma membrane-related
      functions that constitute avoidance learning-related memory in amyloid beta(1-40)
      infused rats.

PMID- 17002671
TI  - Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic
      nephropathy in rats.
AB  - Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals
      and evidence is increasing that these contribute to the development of diabetic
      nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring
      and colouring agent in the indian diet every day and is known to possess anti
      oxidant properties. The present study was designed to examine the effect of
      curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in
      streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single
      intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ
      injection, rats were divided into four groups, namely control rats, diabetic rats
      and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks.
      Renal function was assessed by creatinine, blood urea nitrogen, creatinine and
      urea clearance and urine albumin excretion. Oxidative stress was measured by
      renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide
      dismutase and catalase. Streptozotocin-injected rats showed significant increases
      in blood glucose, polyuria and a decrease in bodyweight compared with age-matched
      control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as
      evidenced by reduced creatinine and urea clearance and proteinuria, along with a
      marked increase in oxidative stress, as determined by lipid peroxidation and
      activities of key anti-oxidant enzymes. Chronic treatment with curcumin
      significantly attenuated both renal dysfunction and oxidative stress in diabetic
      rats. These results provide confirmatory evidence of oxidative stress in diabetic
      nephropathy and point towards the possible anti-oxidative mechanism being
      responsible for the nephroprotective action of curcumin.

PMID- 17002672
TI  - Prostaglandins, capsaicin-sensitive sensory nerves and neutrophil infiltration,
      but not nitric oxide, contribute to cold restraint stress-induced gastric
      adaptation in rats.
AB  - The aim of the present study was to determine the role of prostaglandins (PG),
      nitric oxide (NO) and capsaicin-sensitive sensory nerves in neutrophil
      infiltration in gastric adaptation to cold restraint stress in rats. Wistar rats
      were exposed to single or repeated cold restraint stress for 3.5 h every other
      day for up to 4 days. Prior to repeated stress, rats were pretreated with NG
      nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, s.c.), indomethacin (10 mg/kg,
      s.c.) or capsaicin (125 mg/kg, s.c.). The extent of gastric mucosal lesions was
      evaluated histologically and myeloproxidase (MPO) activity, PGE2, NO and
      calcitonin gene-related peptide (CGRP) levels were measured in gastric tissue.
      Cold restraint stress produced haemorrhagic lesions and reduced PGE2 and CGRP
      levels in the stomach, with an increase in MPO activity and NO levels. Repeated
      stress insults reduced stress-induced gastric damage, NO production and MPO
      activity, with an increase in PGE2 and CGRP levels compared with rats exposed to
      single cold restraint stress. Adaptation to cold restraint stress was prevented
      by indomethacin and capsaicin pretreatment, but not by L-NAME. We conclude that
      the stomach has the ability to adapt to repeated exposure to cold restraint
      stress and that the adaptation, via inhibition of neutrophil infiltration, is
      mediated, at least in part, by endogenous PG and CGRP.

PMID- 17002673
TI  - A proteomic analysis of the acute effects of high-intensity exercise on skeletal
      muscle proteins in fasted rats.
AB  - Quantitative proteomics is a technique that allows for large-scale comparison of
      the levels of individual proteins present in a biological sample. This technique
      has not previously been applied to examine the response of skeletal muscle
      proteins to an acute bout of exercise. In the present study, quantitative
      proteomics was applied to investigate whether the levels of individual skeletal
      muscle proteins are acutely affected by a short bout of high-intensity exercise.
      Gastrocnemius muscle was sampled from fasted rats either at rest, immediately
      following 3 min of high-intensity exercise or after 30 min of recovery. Muscle
      samples were submitted to two-dimensional gel electrophoresis and 61 of the
      resulting protein spots were selected for quantitative analysis. It was found
      that skeletal muscle protein levels were generally not acutely affected by a
      short bout of high-intensity exercise, with only four of the 61 proteins selected
      for analysis being significantly altered. These altered proteins were identified
      using liquid chromatography electrospray ionization-tandem mass spectrometry as
      creatine kinase, troponin T and a combination of heat shock 20 kDa protein and
      adenylate kinase 1. In conclusion, quantitative proteomics is sensitive enough to
      detect acute changes in skeletal muscle protein levels in response to exercise.
      We have found that the levels of most individual skeletal muscle proteins are not
      immediately altered in response to a short bout of high-intensity exercise and
      recovery in fasted rats.

PMID- 17002675
TI  - Renal oxygen delivery: matching delivery to metabolic demand.
AB  - The kidneys are second only to the heart in terms of O2 consumption; however,
      relative to other organs, the kidneys receive a very high blood flow and oxygen
      extraction in the healthy kidney is low. Despite low arterial-venous O2
      extraction, the kidneys are particularly susceptible to hypoxic injury and much
      interest surrounds the role of renal hypoxia in the development and progression
      of both acute and chronic renal disease. Numerous regulatory mechanisms have been
      identified that act to maintain renal parenchymal oxygenation within homeostatic
      limits in the in vivo kidney. However, the processes by which many of these
      mechanisms act to modulate renal oxygenation and the factors that influence these
      processes remain poorly understood. A number of such mechanisms specific to the
      kidney are reviewed herein, including the relationship between renal blood flow
      and O2 consumption, pre- and post-glomerular arterial-venous O2 shunting,
      tubulovascular cross-talk, the differential control of regional kidney blood flow
      and the tubuloglomerular feedback mechanism. The roles of these mechanisms in the
      control of renal oxygenation, as well as how dysfunction of these mechanisms may
      lead to renal hypoxia, are discussed.

PMID- 17002676
TI  - Hypoxia-induced erythropoietin production: a paradigm for oxygen-regulated gene
      expression.
AB  - The mechanisms controlling the expression of the gene encoding for the hormone
      erythropoietin (EPO) are exemplary for oxygen-regulated gene expression. In
      humans and other mammals, hypoxia modulates EPO levels by increasing expression
      of the EPO gene. An association between polycythaemia and people living at high
      altitudes was first reported more than 100 years ago. Since the identification of
      EPO as the humoral regulator of red blood cell production and the cloning of the
      EPO gene, considerable progress has been made in understanding the regulation of
      EPO gene expression. This has finally led to the identification of a widespread
      cellular oxygen-sensing mechanism. Central to this mechanism is the transcription
      factor complex hypoxia-inducible factor (HIF)-1. The abundance and activity of
      HIF-1, a heterodimer of an alpha- and beta-subunit, is predominantly regulated by
      oxygen-dependent post-translational hydroxylation of the alpha-subunit. Non-heme
      ferrous iron containing hydroxylases use dioxygen and 2-oxoglutarate to
      specifically target proline and an asparagine residue in HIF-1alpha. As such, the
      three prolyl hydroxylases (prolyl hydroxylase domain-containing protein (PHD) 1,
      PHD2 and PHD3) and the asparagyl hydroxylase (factor inhibiting HIF (FIH)-1) act
      as cellular oxygen sensors. In addition to erythropoiesis, HIF-1 regulates a
      broad range of physiologically relevant genes involved in angiogenesis,
      apoptosis, vasomotor control and energy metabolism. Therefore, the HIF system is
      implicated in the pathophysiology of many human diseases. In addition to the
      tight regulation by oxygen tension, temporal and tissue-specific signals limit
      expression of the EPO gene primarily to the fetal liver and the adult kidney.

PMID- 17002677
TI  - Renal parenchymal oxygenation and hypoxia adaptation in acute kidney injury.
AB  - The pathogenesis of acute kidney injury (AKI), formally termed acute tubular
      necrosis, is complex and, phenotypically, may range from functional dysregulation
      without overt morphological features to literal tubular destruction. Hypoxia
      results from imbalanced oxygen supply and consumption. Increasing evidence
      supports the view that regional renal hypoxia occurs in AKI irrespective of the
      underlying condition, even under circumstances basically believed to reflect
      'direct' tubulotoxicity. However, at present, it is remains unclear whether
      hypoxia per se or, rather, re-oxygenation (possibly through reactive oxygen
      species) causes AKI. Data regarding renal hypoxia in the clinical situation of
      AKI are lacking and our current concepts regarding renal oxygenation during acute
      renal failure are presumptive and largely derived from experimental studies.
      There is robust experimental evidence that AKI is often associated with altered
      intrarenal microcirculation and oxygenation. Furthermore, renal parenchymal
      oxygen deprivation seems to participate in the pathogenesis of experimental AKI,
      induced by exogenous nephrotoxins (such as contrast media, non-steroidal anti
      inflammatory drugs or amphotericin), sepsis, pigment and obstructive
      nephropathies. Sub-lethal cellular hypoxia engenders adaptational responses
      through hypoxia-inducible factors (HIF). Forthcoming technologies to modulate the
      HIF system form a novel potential therapeutic approach for AKI.

PMID- 17002678
TI  - Intrarenal oxygenation in chronic renal failure.
AB  - In chronic renal failure (CRF), renal impairment correlates with
      tubulointerstitial fibrosis characterized by inflammation, interstitial expansion
      with accumulation of extracellular matrix (ECM), tubular atrophy and vascular
      obliteration. Tubulointerstitial injury subsequent to glomerular sclerosis may be
      induced by proteinuria, leakage of glomerular filtrate or injury to the post
      glomerular peritubular capillaries (hypoxia). In vivo data in animal models
      suggest that CRF is associated with hypoxia, with the decline in renal Po2
      preceding ECM accumulation. Chronic renal failure is characterized by loss of
      microvascular profiles but, in the absence of microvascular obliteration, hypoxia
      can occur by a variety of complementary mechanisms, including anaemia, decreased
      capillary flow, increased vasoconstriction, increased metabolic demand and
      increased diffusion distances due to ECM deposition. Hypoxia regulates a wide
      array of genes, including many fibrogenic factors. Hypoxia-inducible factors
      (HIF) are the major, but not the sole, transcriptional regulators in the hypoxic
      response. In CRF, hypoxia may play a role in the sustained inflammatory response.
      In vitro studies in tubulointerstitial cells suggest that hypoxia can induce
      profibrogenic changes in proximal tubular epithelial cells and interstitial
      fibroblasts consistent with changes observed in CRF in vivo. The effect of
      hypoxia on renal microvascular cells warrants investigation. Hypoxia may play a
      role in the recruitment, retention and differentiation of circulating progenitor
      cells to the kidney contributing to the disease process and may also affect
      intrinsic stem cell populations. Chronic hypoxia in CRF fails to induce a
      sustained angiogenic response. Therapeutic manipulation of the hypoxic response
      may be of benefit in slowing progression of CRF. Potential therapies include
      correction of anaemia, inhibition of the renin-angiotensin system, administration
      of exogenous pro-angiogenic factors to protect the microvasculature, activation
      of HIF and hypoxia-mediated targeting of engineered progenitor cells.

PMID- 17002679
TI  - Intrarenal oxygen in diabetes and a possible link to diabetic nephropathy.
AB  - Diabetic nephropathy is a major cause of morbidity and mortality. The exact
      mechanism mediating the negative influence of hyperglycaemia on renal function
      remains unclear, although several hypotheses have been postulated. The cellular
      mechanisms include glucose-induced excessive formation of reactive oxygen
      species, increased glucose flux through the polyol pathway and formation of
      advanced glycation end-products. The renal effects in vivo of each and every one
      of these mechanisms are even less clear. However, there is growing evidence that
      hyperglycaemia results in altered renal oxygen metabolism and decreased renal
      oxygen tension and that these changes are linked to altered kidney function.
      Clinical data regarding renal oxygen metabolism and oxygen tension are currently
      rudimentary and our present understanding regarding renal oxygenation during
      diabetes is predominantly derived from data obtained from animal models of
      experimental diabetic nephropathy. This review will present recent findings
      regarding the link between hyperglycaemia and diabetes-induced alterations in
      renal oxygen metabolism and renal oxygen availability. A possible link between
      reduced renal oxygen tension and the development of diabetic nephropathy includes
      increased polyol pathway activity and oxidative stress, which result in decreased
      renal oxygenation and subsequent activation of hypoxia-inducible factors. This
      initiates increased gene expression of numerous genes known to be involved in
      development of diabetic nephropathy.

PMID- 17002680
TI  - Intrarenal oxygen and hypertension.
AB  - The kidney has a unique environment that results in relatively low tissue oxygen
      tension (Po2). However, recent studies have shown that renal hypoxia is more
      severe during hypertension and may reflect changes in the way O2 is used. The
      present review summarizes studies that explore the relationship between renal
      oxygen tension (Po2), oxygen consumption and hypertension. More recent studies
      suggest that oxidative stress accompanying hypertension, rather than the elevated
      blood pressure per se reduces Po2. The Po2 in various sections of the kidney
      often reflects the level of oxygen consumption, which varies depending on the
      sites of Na+ reabsorption, a process that consumes nearly 90% of total renal
      oxygen. The efficient use of oxygen for the transport of Na+ in the kidney is
      reduced during hypertension, which may contribute to the resulting hypoxia.
      Conversely, the defect in renal oxygen usage due to oxidative stress may
      exacerbate hypertension in animal models. The goal of many of these studies is to
      determine the impact of renal hypoxia in the generation of hypertension.

PMID- 17002682
TI  - The 21st century renaissance of the basophil? Current insights into its role in
      allergic responses and innate immunity.
AB  - Basophils and mast cells express all the three subchains of the high-affinity
      immunoglobulin E (IgE) receptor Fc epsilon RI and contain preformed histamine in
      the cytoplasmic granules. However, it is increasingly clear that these cells play
      distinct roles in allergic inflammatory disease. Despite their presence
      throughout much of the animal kingdom, the physiological function of basophils
      remains obscure. As rodent mast cells are more numerous than basophils, and
      generate an assortment of inflammatory cytokines, basophils have often been
      regarded as minor players in allergic inflammation. In humans, however, basophils
      are the prime early producers of interleukin (IL)-4 and IL-13, T helper (Th)2
      type cytokines crucial for initiating and maintaining allergic responses.
      Basophils also express CD40 ligand which, in combination with IL-4 and IL-13,
      facilitates IgE class switching in B cells. They are the main cellular source for
      early IL-4 production, which is vital for the development of Th2 responses. The
      localization of basophils in various tissues affected by allergic inflammation
      has now been clearly demonstrated by using specific staining techniques and the
      new research is shedding light on their selective recruitment to the tissues.
      Finally, recent studies have shown that basophil activation is not restricted to
      antigen-specific IgE crosslinking, but can be caused in non-sensitized
      individuals by a growing list of parasitic antigens, lectins and viral
      superantigens, binding to non-specific IgE antibodies. This, together with novel
      IgE-independent routes of activation, imparts important new insights into the
      potential role of basophils in both adaptive and innate immunity.

PMID- 17002683
TI  - Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma
      model.
AB  - Mesenchymal stem cells (MSCs) represent a new tool for delivery of therapeutic
      agents to tumor cells. In this study, we have evaluated the anti-tumor activity
      of human MSCs stably transduced with a retroviral vector expressing the cytokine
      interleukin-12 (IL-12) in a mouse melanoma model. Application of MSC(IL-12) but
      not control MSCs strongly reduced the formation of lung metastases of B16F10
      melanoma cells. The activity of the MSC(IL-12) cells was dependent on the
      presence of natural killer (NK) cells in this experimental setting. Further,
      MSC(IL-12) cells elicited a pronounced retardation of tumor growth and led to
      prolonged survival when injected into established subcutaneous melanoma in a
      therapeutic regimen. The therapeutic effect of the MSC(IL-12) was in part
      mediated by CD8(+) T cells, while NK cells and CD4(+) T cells appeared to play a
      minor role. The anti-tumor effect of MSC(IL-12) cells was of similar efficiency
      as observed for application of naked plasmid DNA encoding IL-12. The presented
      data demonstrate that these two different strategies can induce a similar
      therapeutic anti-tumor efficacy in the mouse melanoma tumor model.

PMID- 17002684
TI  - Time course changes of scratching counts, dermatitis symptoms, and levels of
      cutaneous prostaglandins in NC/Nga mice.
AB  - NC/Nga (NC) mice are known to develop dermatitis resembling atopic dermatitis
      (AD) in conventional (Conv) conditions, but not in specific pathogen-free (SPF)
      conditions. We reported that the ability of skin prostaglandin D(2) (PGD(2))
      production, which might be the endogenous inhibitor of itching, was attenuated in
      skin-lesioned Conv-NC mice. We examined the age-related change in scratching,
      dermatitis symptoms, and skin PGs of SPF- and Conv-NC mice. In Conv-NC, PGD(2)
      increased at 7 weeks, at which scratching counts increased, but dermatitis did
      not develop. PGE(2), PGI(2) and PGF(2alpha) increased at 10 and 13 weeks, at
      which dermatitis developed. The ability to produce skin PGs was examined by
      measuring PGs after application of arachidonic acid or after mechanical
      scratching using a wire brush. In Conv-NC, PGD(2) production at 13 weeks was
      lower than at 7 weeks. In Conv-NC, hematopoietic PGD synthase (hPGDS) expression
      in the skin at 13 weeks was lower than at 7 weeks by Western blotting and
      immunohistochemical analysis. The increase of skin PGD(2) level in the early
      phase of the development of dermatitis is due to the stress of extensive
      scratching, but did not increase in spite of the stress of extensive scratching
      in the late phase, due to decreasing capacity of PGD(2) production attributable
      to decreasing hPGDS expression in Conv-NC mice. These results suggest that a
      decreased ability to produce skin PGD(2) production could enhance scratching and
      aggravate dermatitis in Conv-NC mice.

PMID- 17002685
TI  - Cyclodextrin-induced apoptosis in human keratinocytes is caspase-8 dependent and
      accompanied by mitochondrial cytochrome c release.
AB  - Cyclodextrins (CDs) are cyclic oligosaccharides that are able to form inclusion
      complexes with a variety of substances. For pharmaceutical applications, CD-based
      drug formulations offer important advantages compared with uncomplexed drugs.
      These include improved water solubility of lipophilic drug molecules, increased
      chemical stability, as well as enhanced bioavailability and absorption rate.
      Also, a number of topical formulations for dermal and transdermal drug delivery
      contain CDs. However, the most frequently used CDs - beta-CD and MbetaCD - are
      known to extract cholesterol from plasma membranes and thus to cause cellular
      damage and cell death. In the present study, the influence of various CDs and CD
      derivatives on the human keratinocyte cell line HaCaT was assessed. We found that
      beta-CD and MbetaCD induce apoptosis via the activator caspase-8, which
      subsequently activates the effector caspases-3/-7. Furthermore, beta-CD-induced
      apoptosis is accompanied by mitochondrial cytochrome c release. A significant
      shift from mitochondria into the cytosol was found. These findings may provide
      further rationale to the use of CDs in topical formulations for dermal and
      transdermal drug delivery or as raw material in order to functionalize textiles
      for medical applications.

PMID- 17002686
TI  - Generation and distribution of reactive oxygen species in the skin of hairless
      mice under UVA: studies on in vivo chemiluminescent detection and tape stripping
      methods.
AB  - Although the formation of reactive oxygen species (ROS) in the skin induced by
      the ultraviolet (UV) light has been shown to lead to many cutaneous disorders,
      skin cancer and photoageing, the mechanism and distribution of ROS generation has
      not yet been definitively determined. In the present study, we examined the
      distribution of UVA-induced ROS in the skin of live hairless mice, using our
      proposed in vivo imaging chemiluminescent (CL) method to detect ROS combined with
      a CL probe (cypridina hilgendorfii luciferin analogue; CLA) and tape stripping
      (TS) technique. The CL intensities in the skin of live hairless mice were
      confirmed to significantly increase by UVA exposure. When TS was conducted five
      times in a maximum level after CL measurement following UVA exposure and
      subsequent CLA application, CL intensities due to UVA-induced ROS generation in
      the residual skin decreased to 10% of the original levels; and those in the
      stripped skin on each tape decreased in the stripped order such as 52%, 16%, 11%,
      6% and 5%. Next, CLA was applied and then CL intensities were measured in the
      residual skin after advance 1, 3 and 5 tape strippings, and CL intensities due to
      ROS were detected primarily in the outer layer of the skin. On the basis of these
      results, we concluded that ROS induced by UVA exposure occurs and distributes in
      the outermost layer of the stratum corneum.

PMID- 17002687
TI  - The CX3CL1-CX3CR1 system and psoriasis.
AB  - CX3CL1 is a chemoattractant and adhesion molecule that induces the redistribution
      of CX3CR1-positive inflammatory leucocytes to sites of inflammation. As a
      consequence of their increased expression in plaques of psoriasis, and location
      within genomic regions previously linked to this disease, CX3CL1, and its
      receptor CX3CR1, represent attractive positional and functional 'psoriasis
      susceptibility genes'. To investigate the CX3CL1-CX3CR1 system in psoriasis,
      eight single nucleotide polymorphisms (SNPs) in CX3CL1 and two SNPs in CX3CR1
      were genotyped in 281 psoriasis patients and 184 unrelated controls. Allele,
      genotype and estimated haplotype frequencies were then compared between
      experimental groups. Allele frequency differences between healthy volunteers and
      psoriasis patients revealed associations with two CX3CR1 SNPs (hCV11578468, P =
      0.03 and c_5687_1, P = 0.04). No associations were observed between CX3CL1 SNPs
      and psoriasis. These results support a role for the CX3CL1-CX3CR1 system in the
      pathogenesis of psoriasis and identify SNPs within the chemokine receptors that
      are associated with the disease.

PMID- 17002688
TI  - Approaches for optimizing the calibration standard of Tewameter TM 300.
AB  - Calibration of devices measuring transepidermal water loss (TEWL) is in intensive
      discussion. Comparative studies revealed that comparable measuring systems, e.g.
      open and closed chamber systems, do not always deliver the same results, even
      when expressing the measured values in SI units, namely in g/m(2)/h. Therefore,
      adequate and reliable calibration procedures need to be established. We were able
      to test the reliability of a multi-step calibration algorithm for an open chamber
      system such as Tewameter TM 300. In order to achieve reliable measurements, the
      maintenance of stable microclimate conditions without air turbulences is
      mandatory. The TEWL values should be compared with those determined
      gravimetrically on heated skin simulators. The reproducibility of the results is
      warranted by consecutive measurements on different adjacent spots of a defined
      area. Preheating of the probe sensors is an effective approach for shortening the
      measuring time and gaining a rapid steady-state. The accurate calibration of the
      probe can be checked under laboratory conditions any time. The critical point of
      the calibration and ultimately the accuracy of in vivo measurements maintain the
      steady functional capacity of the probes during the entire duration of continuous
      studies. The studied calibration procedure ensures these requirements.

PMID- 17002689
TI  - Who is really in control of skin immunity under physiological circumstances -
      lymphocytes, dendritic cells or keratinocytes?
AB  - Our views of the skin immunity theatre are undergoing constant change. These not
      only reflect paradigm shifts in general immunology and skin biology, but also
      have profound clinical implications, which call for strategic changes in
      dermatological therapy. Nowhere can this be witnessed at a greater level of
      instructiveness and fascination than when addressing the question posed by this
      new Controversies feature. Thus, after a very long period of dominance by T cells
      and Langerhans cells as 'lead actors' on the skin immunity stage, the lowly
      keratinocyte has recently made an astounding theatrical appearance as a key
      protagonist of the innate skin immunity system, which may control even acquired
      skin immune responses. Further enhancing dramatic complexity and tension, the
      mast cell has entered as an additional actor claiming centre stage, and the
      epidermal Langerhans cell has slipped in a surprise appearance as the chief agent
      of immunotolerance. May you, esteemed reader, enjoy the spectacle offered here by
      selected immunodermatology authorities who double as 'stage managers' pushing
      their respective favourite actors into the limelight. You get everything you may
      expect from a good performance - complete with the impresario's overture that
      lures you into the theatre and sets the stage, competing divas, recently
      discovered new talents and even the critic's digest while the performance is
      still ongoing. By the time the curtain drops, you will have reached your own,
      independent conclusions on how to answer the title question of this play - at
      least for the time being...

PMID- 17002699
TI  - Tissue remodelling in upper airways: where is the link with lower airway
      remodelling?
AB  - Tissue remodelling reported in upper airways include epithelial hyperplasia,
      increased matrix deposition in the nasal or paranasal lining, matrix degradation
      and accumulation of plasma proteins. Genetic influences, foetal exposures and
      early life events may contribute to structural changes such as subepithelial
      fibrosis from an early age. Other structural alterations are related to duration
      of the disease and long-term uncontrolled inflammation. Structural changes may
      increase alteration of the protective functions of the upper airways namely by
      affecting mucociliary clearance and conditioning of inspired air. The sequences
      of tissue changes during wound repair of upper airway mucosa after surgery are
      illustrative of the complexicity of tissue modelling and remodelling and could be
      considered as an important source of information for a better understanding of
      the complex relationship between inflammatory reaction, of the subsequent tissue
      damages and fibroblast metabolism of upper airways.

PMID- 17002700
TI  - Sleep disturbances in allergic diseases.
AB  - Sleep is fundamental for physical and mental health as well as daytime
      performance and represents a crucial aspect in the personal representations of
      well-being. Sleep disturbances in patients with chronic disorders constitute a
      factor that contributes to exacerbate symptoms, complicate management, and affect
      mood and quality of life (QoL). Allergic diseases are a global health problem of
      increasing prevalence that affects up to 15% of the population in Western
      countries. Sleep problems associated with allergic diseases may play a role in
      worsening the burden of illness, contributing to impairment of the QoL. The aim
      of this review was to describe the most common causes leading to sleep
      disturbance in allergic patients and their consequences on the QoL. The possible
      negative effects of treatment on sleep parameters has been also considered.

PMID- 17002701
TI  - Reduced structural proteins in the conjunctival epithelium in allergic eye
      disease.
AB  - AIMS: Allergic eye disease affects up to 20% of the population with varying
      severity. The conjunctival epithelium plays a key role in allergic eye disease.
      The purpose of this study was to determine whether the conjunctival epithelium is
      abnormal in allergic eye disease. METHODS: Conjunctival biopsy samples were taken
      from patients with seasonal allergic conjunctivitis (SAC) 'in' and 'out of
      season' and nonatopic control subjects. Specimens were fixed in glycol
      methacrylate, 2 microm serial sections cut and Image-J used to assess the sites
      and areas of immuno-staining. RESULTS: E-cadherin, CD44, keratins K5/6, K8, K13,
      K14, K18 and pan-keratin immuno-staining were all significantly lower in patients
      'out of season' compared with normal controls. No structural differences in the
      epithelium were observed between the two groups. The epithelium of patients 'in
      season' was thicker and immuno-staining of the above markers similar to controls.
      CONCLUSIONS: The expression of a wide spectrum of epithelial cell adhesion
      proteins and cytoskeletal elements is downregulated in the conjunctiva of SAC
      patients 'out of season' compared with normal controls. We suggest that this
      could have an important impact on the ability of the epithelium to protect itself
      against allergen penetration, potentially influencing the development and course
      of allergic eye disease and offering a novel area for therapeutic control.

PMID- 17002702
TI  - Distinct features of chronic rhinosinusitis with and without nasal polyps.
AB  - BACKGROUND: Based on the presence of nasal polyps on endoscopy, chronic
      rhinosinusitis (CRS) may be clinically divided in CRS with nasal polyps and CRS
      without nasal polyps. It is unclear, whether CRS with nasal polyps and CRS
      without nasal polyps represent different disease entities or just different
      stages of one single disease. In case of one disease, only minor
      histopathological differences between CRS with small early-stage polyps
      (CRSNP((+))) and CRS without nasal polyps (CRSNP(-)) were expected. METHODS:
      Patients with CRSNP((+)) confined to the infundibular region or CRSNP(-) were
      selected. Histochemical and immunohistochemical characterization of ethmoidal
      mucosa was performed on formalin-fixed and paraffin-embedded tissue specimens.
      Frequency and distribution of eosinophils, neutrophils, mast cells, IgE(+) cells,
      macrophages, B- and T-cell subsets, natural killer cells, plasma cells and goblet
      cells were assessed. In addition, the thickness of the basal membrane was
      evaluated. RESULTS: Nine CRS patients without detectable polyps, and 11 patients
      with small early-stage polyps confined to the infundibular region were selected.
      Despite adjacent polyp stage, the amount of round cell infiltration (P < 0.05),
      number of eosinophils (P < 0.05), and plasma cells (P < 0.01) significantly
      differed in the ethmoidal specimens from patients of the two groups. CONCLUSION:
      Substantial histopathological differences were observed in ethmoidal mucosa of
      CRSNP((+)) and CRSNP(-) patients. Thus, the results of this investigation support
      the concept that CRS with nasal polyps and CRS without nasal polyps are two
      different disease entities rather than different stages of one single disease,
      but may also be interpreted as a higher degree of inflammation.

PMID- 17002703
TI  - Differentiation of chronic sinus diseases by measurement of inflammatory
      mediators.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) clinically is a heterogeneous group of
      sinus diseases, which may cover different disease entities, or may represent a
      disease continuum. Studying inflammatory cells and mediators in clearly defined
      disease subgroups may lead to a better differentiation of chronic sinus diseases.
      METHODS: Sinonasal mucosal tissue from 10 nasal polyp (NP) patients, 13 cystic
      fibrosis patients (CF-NP), eight CRS subjects without polyps, and nine control
      patients were stained for CD3, CD25, CD68, CD20, myeloperoxidase (MPO), CD138 and
      tissue homogenates were assayed for eotaxin, interleukin (IL)-1beta, IL-2sRalpha,
      IL-5, interferon (IFN)-gamma, IL-8, transforming growth factor (TGF)-beta1, tumor
      necrosis factor-alpha, and MPO by enzyme-linked immunosorbent assay or UNICAP
      system. RESULTS: Nasal polyp and CF-NP showed increased numbers and activation of
      T cells, while only NP displayed an increase in plasma cells. Nasal polyp had
      significantly higher levels of eosinophilic markers [eosinophils, eotaxin, and
      eosinophil cationic protein (ECP)] compared with CRS, controls and CF-NP. Chronic
      rhinosinusitis was characterized by a Th1 polarization with high levels of IFN
      gamma and TGF-beta, while NP showed a Th2 polarization with high IL-5 and
      immunoglobulin (Ig) E concentrations. Nasal polyp and CF-NP were discriminated by
      edema from CRS and controls, with CF-NP displaying a very prominent neutrophilic
      inflammation. CONCLUSION: Based on cellular and mediator profiles, we suggest
      that CRS, NP, and CF-NP are distinct disease entities within the group of chronic
      sinus diseases.

PMID- 17002704
TI  - Oxidative stress in nonallergic nasal polyps associated with bronchial
      hyperresponsiveness.
AB  - BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of upper
      airway with unknown etiology. NP is frequently associated with asthma; the
      interaction between these comorbidities remains interesting. Oxidative stress has
      been implicated in the pathophysiology of NP and asthma. The aim of this study is
      to investigate the significance of oxidative stress in sinonasal
      microenvironments by evaluating its association with clinopathological parameters
      and its impacts on the pathogenesis of bronchial hyperresponsiveness (BHR) in NP.
      METHODS: Polyp biopsy specimens were obtained from 20 nonallergic patients;
      control mucosas were obtained from 20 volunteers. The levels of free radicals in
      the tissues and in blood were determined by a sensitive chemiluminescence (CL)
      method. NP patients were substratified into three subgroups, NP without BHR, NP
      with asymptomatic BHR, and NP with BHR and asthma by the results of provocative
      testing. Four histological characteristics of NP, inflammatory cells, eosinophil
      infiltration, edema and fibrosis were estimated and applied to correlate with the
      tissue-CL. RESULTS: The mean CL level in polyp-tissues, but not in blood, was
      higher than in the control specimens. In NP patients, tissue-CL was associated
      with endoscopy score; high tissue-CL levels were positively correlated with the
      abundance of inflammatory cells and eosinophils. Tissue-CL and endoscopy score
      were associated with BHR/asthma phenotype. CONCLUSION: These results suggest an
      important role for oxidative stress in the pathophysiology of NP and a causal
      relation between oxidative stress and inflammatory cells, especially the
      eosinophils. Free radical levels in polyp-tissues associated with NP severity and
      with BHR/asthma phenotype in nonallergic NP patients.

PMID- 17002705
TI  - Incidence and remission of self-reported allergic rhinitis symptoms in adults.
AB  - BACKGROUND: A few studies have examined the incidence and remission of allergic
      rhinitis (AR) in the same general population. METHODS: A questionnaire focused on
      respiratory symptoms and airway diseases was mailed out in 1992 and in 2000 to
      the same subjects. Of 4933 subjects, in 1992 aged 20-59 years, 4280 (86.8%)
      answered at both occasions. AR was defined on self-reported AR and a simultaneous
      report of nasal symptoms provoked by exposure either to tree-, grass-pollen,
      furred animals or house dust. Multiple logistic regression adjusted for age and
      gender was used to analyze potential predictors, reported in 1992, for incidence
      and remission of AR. RESULTS: The prevalence of AR increased from 12.4% in 1992
      to 15.0% in 2000. The incidence of AR from 1992 to 2000 was 4.8%, while 23.1% of
      the cases with AR in 1992 stated no AR symptoms in 2000 indicating remission. The
      highest incidence was seen in the youngest age group (20-29 years), whereas
      remission was highest in the oldest age group (50-59 years). Asthma symptoms
      during the last year (as reported in 1992) predicted increased incidence of AR
      and less chance for remission, 1.89 (95%CI 1.08-3.31) and 0.52 (0.31-0.87),
      respectively. Family histories of AR or asthma predicted increased incidence of
      AR 1.99 (1.42-2.80) and 1.62 (1.10-2.37), respectively, but were not associated
      with chance for remission, OR = 1.23 (0.81-1.87) and 0.94 (0.60-1.48).
      CONCLUSION: This study showed that AR became more common between 1992 and 2000,
      but also indicated remission in about 20% of the cases within the 8-year period,
      particularly in older ages. Asthma seems to be associated with higher risk for AR
      as well as less chance for remission, while heredity of asthma (or AR) may only
      be associated with the risk for the development and not remission of AR.

PMID- 17002706
TI  - Swimming pool attendance and hay fever rates later in life.
AB  - BACKGROUND: Exposure to chlorination by-products through swimming pool attendance
      showed adverse health effects on children. The aim of our study was to assess
      whether pool attendance in childhood would be related to higher rates of allergic
      diseases in adulthood, with special regard to hay fever. METHODS: 2606 adults
      aged 35-74 years provided retrospectively collected information on swimming pool
      attendance and medical history, including data on atopic diseases. Information
      was assessed by a combination of a personal interview and a self-administered
      questionnaire. Logistic regression models were applied to study associations
      between hay fever and swimming pool attendance, adjusted for potentially relevant
      confounders, such as age, gender, region, education and smoking. RESULTS: Higher
      rates of hay fever could be seen when frequently exposed at school age (aOR:
      1.74, 95% CI: 1.09-2.77), frequently exposed during the past 12 months (aOR:
      1.32, 95% CI: 0.92-1.89) and ever exposed (aOR: 1.65, 95% CI: 0.98-2.78).
      Strongest associations were found for the youngest subjects and were dose-related
      to the extent of current and school-age pool attendance. CONCLUSIONS: Impaired
      integrity of the lung epithelial by exposure to chlorination by-products might
      facilitate a closer contact to allergens and therefore could result in higher
      rates of hay fever.

PMID- 17002707
TI  - Influence of physical inactivity on the prevalence of hay fever.
AB  - BACKGROUND: Atopic diseases constitute a major public health problem, increasing
      constantly in frequency and severity. While treatments are improving, the main
      cause for an increasing trend of hay fever and its definite triggers remain
      unclear. The aim of our study was to assess whether physical inactivity could be
      a risk factor for hay fever. METHODS: We analysed data of a cohort of children
      aged 5-14 years at baseline (1992-1993) who were followed up until 2003-2005.
      Parental-reported information on physical activity (being active, doing sports)
      was obtained for 2429 children participating at the baseline survey (active: n =
      1923; semi-active: n = 364; inactive: n = 142). A total of 1703 children (70.1%)
      were reapproached at least once during follow-up. Logistic regression models were
      applied to study associations between hay fever, allergic sensitization and
      physical activity, adjusted for potentially relevant confounders such as age,
      gender, study site, parental education, breastfeeding, crowding, daycare,
      dampness or visible moulds, contact to cats, current or prior environmental
      tobacco smoke exposure and parental atopy. RESULTS: Significantly higher rates of
      hay fever were seen for inactive children [aOR 2.39 (95% CI 1.31-4.36) for
      baseline survey 1992-1993 and aOR 1.76 (95% CI 1.14-2.71) for the follow-up
      period until 2005]. In addition, the relative risk of incident cases of hay fever
      increased depending on inactivity [aRR 1.50 (95% CI 1.05-2.13)]. No association
      was found between physical inactivity and allergic sensitization assessed by
      radioallergosorbent test determinations. CONCLUSIONS: Although the underlying
      biological mechanisms could not be clarified, increasing physical activity in
      childhood is suggested to prevent hay fever.

PMID- 17002708
TI  - The prescriptions frequencies and patterns of Chinese herbal medicine for
      allergic rhinitis in Taiwan.
AB  - BACKGROUND: The evaluation of Chinese herbal medicines (CHM) to allergic rhinitis
      (AR) by large-scale pharmaco-epidemiological study is not ease found, although
      CHM had been reported to have potential effect for AR in some clinical trials.
      AIMS OF THE STUDY: To explore the frequency and pattern of CHM prescriptions on
      AR, we have the study by analysing the population-based CHM database in Taiwan.
      METHODS: The way for this study was linked and processed the complete traditional
      Chinese medicine database for Taiwanese recorded in the year 2002. The diagnosis
      of AR was extracted with the only single ICD-9 Code of 477 to calculate the
      frequency and pattern of prescriptions. Association rule was applied to analyse
      co-prescription of CHM for patients with AR. RESULTS: In the year 2002, among the
      22 520 776 valid beneficiaries of the National Health Insurance, Taiwan, 914 612
      subjects (3.8% of the total valid beneficiaries) have diagnosed AR. There were
      35.6% of AR patients been treated by CHM. The peak age of AR patients treated by
      CHM was at the first decade (0-10). For the AR patients, the most common Chinese
      herbal formula prescription was Shin-yi-qing-fei-tang, or Angelica dahurica (Bai
      zhi) for the single Chinese herb. While for the combination treatments the most
      common prescription was the two formulae, Xiao-qing-long-tang and Shin-yi-san.
      CONCLUSIONS: Because of the high utilization rate of the CHM treatment for AR, a
      large-scale randomized trial warrants further research for its efficacy and
      safety.

PMID- 17002709
TI  - Effects of intranasal corticosteroid on nasal adenosine monophosphate challenge
      in persistent allergic rhinitis.
AB  - BACKGROUND: Response to a single dose nasal adenosine monophosphate challenge has
      been used as a surrogate inflammatory marker for allergic rhinitis. Attenuation
      of response following intranasal corticosteroid would further validate the
      challenge. OBJECTIVE: To assess the effect of 4 weeks of 200 mcg once daily
      mometasone furoate nasal spray on a simplified (single 160 mg dose) nasal
      adenosine monophosphate challenge. METHODS: Twenty participants with persistent
      allergic rhinitis completed a double blind placebo-controlled crossover study.
      Outcome measures were the peak nasal inspiratory flow and total nasal symptoms
      score responses to nasal adenosine monophosphate challenge, as well as
      domiciliary peak nasal inspiratory flow and patient symptom diary cards. RESULTS:
      Mometasone significantly (P < 0.05) attenuated response time profiles vs. placebo
      for peak nasal inspiratory flow but not total nasal symptom scores. For the
      maximum percentage fall this amounted to a mean difference of 9.6% (95%
      confidence interval 1.3-17.9%). The coefficient of variation for repeatability
      was 48.7%. Improvements were seen in prechallenge and domiciliary measurements of
      peak nasal inspiratory flow (both P < 0.05) and total nasal symptom scores (both
      P < 0.01). CONCLUSIONS: Mometasone attenuates the peak nasal inspiratory flow
      response to a single 160 mg nasal adenosine monophosphate challenge. Such
      challenges have been shown to be sensitive to the effects of antihistamines,
      antileukotrienes and now nasal steroids. This further supports their application
      as surrogate inflammatory markers for therapeutic trials in allergic rhinitis,
      potentially as 20 min challenges which can be conducted in a non-hospital
      setting.

PMID- 17002710
TI  - Endocrine disrupters--potential modulators of the immune system and allergic
      response.
AB  - Endocrine disrupters (EDs) are environmental pollutants of industrial or
      agricultural origin (e.g. herbicides, fungicides, insecticides, industrial
      chemicals) that may influence health of wildlife and human. Endocrine-disrupting
      effect is obtained by mimicking the action of the steroid hormones and has been
      associated with several reproductive disorders as well as cancerogenesis both in
      animals and humans. EDs can also influence synthesis of cytokines,
      immunoglobulins, and cell mediators as well as immune cell activation and
      survival. Modulation by EDs of interleukin-4 production, Th1/Th2 balance and IgE
      production suggest their potential effect on allergic immune responses. The aim
      of this review was to summarize data indicating a potential effect of EDs
      exposure on the immune system and allergic responses.

PMID- 17002711
TI  - Incorporating a gender dimension in food allergy research: a review.
AB  - Sex and gender are the major determinants of health and disease in both men and
      women. The aim of this review paper was to examine differences in gender and sex
      in relation to the prevalence and effects of food allergy. There are still major
      gaps in our knowledge about the kinds of processes which shape men's and women's
      perceptions and experiences of food allergy. The expression and experience of
      health and illness may be moderated by variables such as biological
      vulnerability, exposure to health risks, perception of symptoms, evaluation of
      risk, information processing and role expectations. This review highlights the
      complex links between biological sex, gender, and health in general and offers a
      synthesis of how these may interact to produce sex and gender differences in
      biopsychosocial manifestations of food allergy. Implications for research and
      public health practice are discussed.

PMID- 17002712
TI  - Inhaled formaldehyde exposure: effect on bronchial response to mite allergen in
      sensitized asthma patients.
AB  - BACKGROUND: Formaldehyde, an indoor air pollutant, is known to be an irritant and
      an etiologic factor in occupational asthma. An epidemiologic study suggests that
      it may also increase the risk of childhood asthma for concentrations above 60
      microg/m(3). AIM: To evaluate the influence of pre-exposure to low-dose
      formaldehyde (100 microg/m(3) in 30 min according to the World Health
      Organization's recommended maximum value for indoor environments) on bronchial
      response to Dermatophagoides pteronyssinus. METHOD: Nineteen asthmatic subjects
      were included. Each subject underwent a mite allergen bronchial challenge test
      immediately after a standardized exposure in a chamber to formaldehyde or air
      (random order). Induced sputum were collected 24 h before and after mite
      challenge. RESULTS: After formaldehyde inhalation, patients developed an
      immediate bronchial response at a significantly lower dose of mite allergen than
      after air exposure (the geometric mean PD(20) for Der p 1 was 34.3 ng after
      formaldehyde and 45.4 ng after placebo, P = 0.05). The late-phase reaction,
      expressed as the maximum fall in forced expiratory volume in 1 s (FEV(1)) from
      baseline, was significantly higher after formaldehyde (15%vs 11%, P = 0.046).
      CONCLUSION: Our study demonstrated that exposure to low levels of formaldehyde
      significantly enhanced bronchial responsiveness to mite allergen in mite
      sensitized subjects with asthma.

PMID- 17002713
TI  - Decrease of cytotoxic T cells in allergic asthma correlates with total serum
      immunglobulin E.
AB  - BACKGROUND: Allergic asthma has been linked to an increase in T-helper type 2
      like cytokines and T cells, but there is growing evidence for a role of
      lymphocyte-mediated cytotoxic mechanisms in the pathogenesis of asthma.
      Therefore, we investigated the cytotoxic potential of different lymphocyte
      subpopulations in patients with allergic asthma. METHODS: Granzyme A, B, K, and
      perforin expression in peripheral blood lymphocytes was analyzed using flow
      cytometry. Soluble granzymes were measured in serum using specific enzyme-linked
      immunosorbent assays. RESULTS: Asthmatics had significantly decreased percentages
      of granzyme and perforin-positive CD4 T cells compared with non-atopic controls.
      In patients with asthma, the granzyme B and perforin-positive subset of CD8(+) T
      cells and natural killer T cells, which represent more differentiated cell
      populations, were significantly reduced, while this was not observed in the less
      differentiated granzyme K(+) subsets. In addition, the serum concentrations of
      granzyme B were significantly reduced in patients with asthma, while granzyme K
      concentrations were not different. Interestingly, there was a negative
      correlation between granzyme A, B and perforin expression in T cell subsets as
      well as serum granzyme B concentrations and total serum immunglobulin E. In CD3
      negative natural killer cells, no differences in granzyme or perforin expression
      between patients with asthma and controls were detected. CONCLUSION: In allergic
      asthma, cytotoxic T lymphocyte subsets of a more differentiated phenotype are
      significantly decreased and this is correlated to serum immunglobulin E levels.

PMID- 17002714
TI  - Allergy to goat and sheep milk without allergy to cow's milk.
AB  - BACKGROUND: Cow's milk (CM) allergy is the most frequent cause of food allergy in
      infants. Most children who are allergic to CM are also sensitized to whey
      proteins and/or to the casein fraction and many of them cannot tolerate goat's or
      sheep's milk (GSM) either. Conversely, the GSM allergies that are not associated
      with allergic cross-reactivity to CM are rare. METHODS: Twenty-eight children who
      had severe allergic reactions, including anaphylaxis, after consumption of GSM
      products but tolerated CM products were recruited in a retrospective study. Whole
      casein and whey proteins were fractionated from CM and GSM. beta-Lactoglobulin
      and the different caseins were isolated, purified and used to perform enzyme
      allergosorbent tests (EAST) and EAST inhibition studies with the sera of the
      allergic children. RESULTS: Clinical observations, skin prick testing and
      immunoglobulin (Ig)E-binding studies confirmed the diagnosis of GSM allergy
      without associated CM allergy. EAST determinations demonstrated that GSM allergy
      involves the casein fraction and not whey proteins. Cow's milk caseins were not
      at all or poorly recognized by the patient's IgE, while alphaS(1)-, alphaS(2)-
      and beta-caseins from GSM were recognized with a high specificity and affinity.
      In all cases, increasing concentrations of CM caseins failed to inhibit the
      binding of patient's IgE to sheep or goat milk caseins, whereas this binding was
      completely inhibited by GSM caseins. CONCLUSIONS: The characteristics of GSM
      allergy differ from those of the CM allergy because it affects older children and
      appears later. CM products do not elicit any clinical manifestation in GSM
      allergic patients, whereas CM allergic patients, usually cross-react to GSM. In
      all the GSM allergic children, the IgE antibodies recognized the caseins but not
      the whey proteins. Moreover, IgE specificity and affinity was high to GSM and
      lower to CM caseins despite their marked sequence homology. Doctors and allergic
      individuals should be aware that GSM allergy requires a strict avoidance of GSM
      and milk-derived products because reactions could be severe after ingestion of
      minimal doses of the offending food.

PMID- 17002715
TI  - Simultaneous exposure of several allergens has an additive effect on
      multisensitized basophils.
AB  - BACKGROUND: Patients immunoglobulin (Ig)E-sensitized to more than one allergen in
      their environment often have more symptoms than mono-sensitized individuals,
      which indicates that the allergens may have an additive effect. In order to study
      if such an effect could be detected on the inflammatory, cellular level,
      multisensitized basophils were challenged with various dose combinations of two
      relevant allergens. METHODS: Basophils from patients IgE-sensitized to
      timothy/cat, birch/cat, timothy/mite and cat/mite were challenged with serial
      dilutions of different combinations of the two allergens. The basophil response
      was measured as CD63 expression analysed by flow cytometry. RESULTS: The doses of
      each allergen in the pair had an additive effect resulting in a shift of the dose
      response curve to higher CD63 percentages and higher CD-sens. CONCLUSIONS: If a
      patient has IgE antibodies and thus sensitized basophils to more than one
      allergen, to which he is simultaneously exposed, the additive effect should be
      considered. Even low concentrations of IgE antibodies could be of clinical
      relevance in such a situation.

PMID- 17002717
TI  - Teicoplanin-induced anaphylaxis.

PMID- 17002718
TI  - Plasma lycopene concentration is low in subjects with stable asthma.

PMID- 17002719
TI  - Allergy due to head lice (Pediculus humanus capitis).

PMID- 17002721
TI  - Editorial: clinical trials in tropical diseases: a politically incorrect view.

PMID- 17002722
TI  - A double-blind randomized controlled trial of antenatal mebendazole to reduce low
      birthweight in a hookworm-endemic area of Peru.
AB  - OBJECTIVE: To assess the effect on birthweight of antenatal mebendazole plus iron
      vs. placebo plus iron in a highly hookworm-endemic area. METHODS: Double-blind,
      randomized controlled trial set in rural and peri-urban communities in the
      Peruvian Amazon region. A total of 1042 second trimester pregnant women between
      the ages of 18 and 44 years were recruited from April to November 2003, and
      followed to July 2004. Women were randomly assigned to receive either mebendazole
      (500 mg single dose) plus iron supplements (60 mg elemental iron daily) or
      placebo plus iron supplements. The primary outcome was mean infant birthweight
      and secondary measures included proportion of low birthweight babies and maternal
      anaemia. RESULTS: The prevalence of hookworm infection was 47.5%. There were no
      differences between intervention groups in mean birthweight (3104 g vs. 3090 g, P
      = 0.629), proportion of low birthweight (<2500 g; 8.1%vs. 8.7%, P = 0.755) or
      maternal anaemia in the third trimester [33.0% (158/479) vs. 32.3% (152/471), P =
      0.815]. However, the proportion of very low birthweight (<1500 g) was
      significantly lower in the mebendazole group [0% (0/479) vs. 1.5% (7/471), P =
      0.007]. CONCLUSIONS: This trial provides additional evidence for the use of
      anthelmintics, over and above iron supplementation, within antenatal care
      programmes in hookworm-endemic areas. Benefits of de-worming may be higher in
      countries not having an antenatal iron supplementation programme or where
      intensity of hookworm infections is higher.

PMID- 17002723
TI  - Hepatitis B seroprevalence in Thailand: 12 years after hepatitis B vaccine
      integration into the national expanded programme on immunization.
AB  - OBJECTIVES: To evaluate the impact of the universal hepatitis B (HB) vaccination
      programme on the prevalence of hepatitis B surface antigen (HBsAg) carriers and
      immunity to HB virus infection among children <18 years and to determine the HB
      seroprevalence in the Thai population. METHODS: We enrolled people in four
      provinces, including Chiangrai, Udon Thani, Chonburi and Nakhon Si Thammarat to
      geographically represent populations in the North, Northeast, Center and South of
      the country respectively. Serology for HBsAg, anti-hepatitis B surface (anti
      HBs), and anti-hepatitis B core (anti-HBc) was tested using ELISA commercial
      kits. In total, 6213 subjects aged 6 months to 60 years from the four provincial
      hospitals and two to three district hospitals of each participating province
      participated. RESULTS: Overall HBsAg, anti-HBs, and anti-HBc seropositive rates
      amounted to 4%, 41.6% and 26.5% respectively. Of 2887 participants aged 6 months
      to 18 years, 2303 were born after (group I) and 584 prior to (group II) HB
      vaccine integration into the expanded programme on immunization of each
      participating province. The HBsAg seropositive rate was 0.7% among group I
      children and 4.3% among group II children. The prevalence rate of anti-HBc was
      2.9% in group I and 15.8% in group II. In children under 18 years, the HBsAg
      carrier rate was 0.98% among complete vaccinees and 1.36% among participants
      without vaccination. CONCLUSIONS: This finding supports the efficacy of universal
      HB immunization in reducing the prevalence of HB infection in Thailand which is a
      highly endemic country.

PMID- 17002724
TI  - Artesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for
      treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical
      trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes.
AB  - We undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate +
      sulphadoxine-pyrimethamine (AS + SP) in 180 children of age 6-59 months with
      uncomplicated malaria in Democratic Republic of Congo. Children were randomly
      allocated to receive 3 days observed treatment of AS + AQ (n = 90) or 3 days of
      AS + SP (n = 90). Primary efficacy outcomes were 28-day parasite recurrence
      rates, and recrudescence rates were adjusted by genotyping to distinguish new
      infection and recrudescence. In addition, we determined the prevalence of
      molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28
      parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ
      group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P = 0.009).
      After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for
      AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P = 0.02). There was no
      significant difference between the two arms in time to parasite clearance, fever
      clearance and gametocyte clearance. Parasite genotyping showed high frequencies
      of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular
      SP-resistance markers, with 57% of the samples showing more than three mutations
      linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype,
      confirming that SP treatment failure rates are likely to be high. AS + AQ had
      significantly higher efficacy than AS + SP. These results contributed to the
      subsequent change to AS + AQ as first-line regimen in the country. Efforts to
      properly implement the new protocol and maintain adherence at acceptable levels
      should include health staff and patient sensitization. The 6.8% recrudescence
      rate indicates that AS + AQ should be monitored closely until a more effective
      artemisinin combination therapy regimen is needed and can be introduced.

PMID- 17002725
TI  - Malaria control using indoor residual spraying and larvivorous fish: a case study
      in Betul, central India.
AB  - OBJECTIVES: To assess the impact of intensified malaria control interventions in
      an ethnic minority community in Betul using existing tools. METHODS: Two rounds
      of indoor residual spraying with synthetic pyrethroid insecticide were applied
      and larvivorous fish introduced, followed by intensive surveillance for early
      detection of Plasmodium falciparum with rapid diagnostic tests and prompt
      treatment with sulphadoxine pyrimethamine. RESULTS: Pre-intervention surveys
      revealed a very high fever rate in the community in all age groups with a slide
      positivity rate of >50% with >90%P. falciparum. The post-intervention phase
      showed a sharp steady decline in number of malaria cases (beta 0.972; P < 0.0001,
      95% CI 0.35-0.47). Monitoring of entomological results revealed a significant
      decline in both Anopheles species and An. culicifacies (P < 0.0001). CONCLUSION:
      A combination of indoor residual spraying and early detection and prompt
      treatment complemented by rapid diagnostic tests and larvivorous fishes
      successfully brought malaria under control. These approaches could be applied in
      other regions of different endemicity to control malaria in India.

PMID- 17002726
TI  - Comprehensive findings on clinical, bacteriological, histopathological and
      therapeutic aspects of cutaneous tuberculosis.
AB  - OBJECTIVE: To define the bacteriological and histological correlates of the three
      predominant clinical forms of cutaneous tuberculosis and to evaluate the efficacy
      of a 9-month daily regimen containing rifampicin and isoniazid. METHODS: In the
      dermatological clinics of two major teaching hospitals in Chennai, 213 patients
      with suspected clinical manifestations of cutaneous tuberculosis underwent
      examination and a skin biopsy for bacteriological and histological tests. They
      were treated with a daily regimen of rifampicin and isoniazid for 9 months and
      follow-up for 3 years. RESULTS: Bacteriological and/or histological confirmation
      of tuberculosis was obtained in 88% of the cases. Lupus vulgaris lesions were
      seen mainly in the extremities and verrucosa cutis occurred predominantly on the
      sole and foot, while the cervical and axillary regions were the commonest sites
      for scrofuloderma. Ninety-two per cent of the patients showed resolution of the
      lesions within the first 6 months of chemotherapy; 1% failed to respond to this
      regimen. There was no relapse in any of the cases during the follow-up period of
      3 years. CONCLUSIONS: Clinical findings were adequate to identify major forms of
      cutaneous tuberculosis as evidenced by bacteriological and histopathological
      examination. A daily regimen of rifampicin and isoniazid for 9 months was
      effective in treating cutaneous tuberculosis.

PMID- 17002727
TI  - Effect of month of vaccine administration on antibody responses in The Gambia and
      Pakistan.
AB  - OBJECTIVE: To explore the relationship between calendar month of administration
      and antibody (Ab) response to vaccination in subjects from The Gambia and
      Pakistan, two countries with distinct patterns of seasonality. METHODS: Three
      cohorts were investigated: Responses to rabies and pneumococcal vaccine were
      assessed in 472 children (mean age 8 years, males 53%) from rural Gambia.
      Responses to tetanus, diphtheria and hepatitis B (HBsAg) were investigated in 138
      infants also from The Gambia (birth to 52 weeks of age, males 54%). Responses to
      rabies and Vi typhoid vaccines were assessed in 257 adults from Lahore, Pakistan
      (mean age 29.4 years, males 57%). RESULTS: In Gambian children, significant
      associations were observed between month of vaccination and Ab response for the
      pneumococcal and rabies vaccines. As no consistent pattern by month was observed
      between the responses, it is assumed that different immunomodulatory stimuli or
      mechanisms were involved. In Pakistani adults, a significant pattern by month of
      vaccination was observed with both rabies and typhoid vaccine. No monthly
      influences were observed in the infant study to the tetanus, diphtheria or the
      HbsAg vaccines. CONCLUSIONS: Antibody responses to certain specific vaccines are
      influenced by month of administration. Further research is required to elucidate
      the precise mechanisms explaining these observations, but a co-stimulatory effect
      of seasonally variable environmental antigens is a likely cause. Future studies
      of Ab response to vaccination in countries with a seasonally dependent
      environment should consider month of vaccination when interpreting study
      findings.

PMID- 17002728
TI  - Point-of-use water treatment and diarrhoea reduction in the emergency context: an
      effectiveness trial in Liberia.
AB  - Communicable diseases are of particular concern in conflict and disaster-affected
      populations that reside in camp settings. In the acute emergency phase,
      diarrhoeal diseases have accounted for more than 40% of deaths among camp
      residents. Clear limitations exist in current water treatment technologies, and
      few products are capable of treating turbid water. We describe the findings of a
      12-week effectiveness study of point-of-use water treatment with a flocculant
      disinfectant among 400 households in camps for displaced populations in Monrovia,
      Liberia. In intervention households, point-of-use water treatment with the
      flocculant-disinfectant plus improved storage reduced diarrhoea incidence by 90%
      and prevalence by 83%, when compared with control households with improved water
      storage alone. Among the intervention group, residual chlorine levels met or
      exceeded Sphere standards in 85% (95% CI: 83.1-86.8) of observations with a 95%
      compliance rate.

PMID- 17002729
TI  - Mortality rate and years of life lost from unintentional injury and suicide in
      South India.
AB  - We calculated mortality rates and years of life lost because of unintentional
      injuries and suicides using community based information obtained prospectively
      over a 7-year period, from 1998 to 2004, among a rural and peri-urban population
      of 108,000 in South India. Per 100,000 population the total mortality rate for
      unintentional injuries and suicides combined was 137.1, with 54.9 for
      unintentional injuries and 82.2 for suicides respectively. Hanging and self
      poisoning with pesticides were the preferred means of suicide. Unintentional
      injuries and suicides resulted in 26.9% of total life years lost over the study
      period while 18.9% of all deaths in the population were attributable to
      unintentional injuries and suicides in the same period. The high burden is
      particularly notable in the 15-29 age group, where up to 70% of years of life
      lost are due to injury. The burden of injuries reported in this study is
      significantly higher than the figures reflected in available reports for India
      and is likely due to the under reporting in routine mortality statistics,
      particularly of suicides.

PMID- 17002730
TI  - Risk factors for injuries in young children in four developing countries: the
      Young Lives Study.
AB  - OBJECTIVE: To assess the occurrence of child injury in four developing country
      settings and to explore potential risk factors for injury. METHODS: Injury
      occurrence was studied in cohorts of 2000 children of age 6-17 months at
      enrolment, in each of Ethiopia, Peru, Vietnam and India (Andhra Pradesh).
      Generalized estimating equation models were used to explore potential risk
      factors for child injury. RESULTS: Occurrence of child injury was high in all
      countries. Caregiver depression emerged as a consistent risk factor for all types
      of injury measured (burns, serious falls, broken bones and near-fatal injury)
      across all countries. Other risk factors also showed consistent associations,
      including long-term child health problems, region of residence and the regular
      care of the child by a non-household member. CONCLUSIONS: This report provides
      further evidence of the importance of childhood injury in developing countries
      and emphasizes the importance of including infants in injury research and
      prevention strategies. It provides strong evidence of an association between
      caregiver mental health and child injury risk and contributes to the limited
      knowledge base on risk factors for child injury in developing countries.

PMID- 17002731
TI  - Finding patients eligible for antiretroviral therapy using TB services as entry
      point for HIV treatment.
AB  - OBJECTIVE: To estimate the proportion of antiretroviral therapy (ART) eligible
      adults (15-49 years) with tuberculosis potentially identifiable through
      tuberculosis services using a CD4 count below 350 cells/mm3 as cut-off value for
      ART initiation. METHODS: Using TB notification rate data, HIV seroprevalence
      data, and estimates of the size of the adult population (15-49 years) in 18 sub
      Saharan African countries with an HIV seroprevalence of > 5%, calculations of the
      number of ART eligible adults with tuberculosis presenting to tuberculosis
      services were made. Assumptions were made on the tuberculosis notification rates
      in the age-group 15-49 years, the HIV-infected population with a CD4 count below
      350 cells/mm3 and the relative risk of developing tuberculosis, and average
      duration from HIV infection to death. The probability of having a CD4+ count
      below 350 cells/mm3 given a diagnosis of tuberculosis was estimated using Bayes'
      theorem, and estimates of the number of patients with a CD4 count below 350
      cells/mm3 identifiable through tuberculosis were made. The number needed to
      screen to identify one ART eligible patient through tuberculosis services was
      estimated for each country. RESULTS: ART eligible adults with tuberculosis
      potentially identifiable through tuberculosis services in the 18 countries ranged
      from 2% to 18% of the total HIV-infected adult population with a CD4+ count below
      350 cells/mm3 and would average 10% of all such HIV patients. The number needed
      to screen to identify ART eligible patients through tuberculosis services ranged
      from 1.4 to 4.2, against 8.6 to 65.4 if adults aged 15-49 are randomly screened
      for low CD4 counts. CONCLUSION: Tuberculosis services are an important entry
      point for identifying ART eligible patients. Given that dually infected patients
      identified through tuberculosis services contributed to 10% of the HIV-infected
      adult population with a CD4 cell count below 350 cells/mm3 in the 18 sub-Saharan
      African countries, major efforts are required beyond the tuberculosis services in
      detecting patients that should benefit from ART. However, the low number needed
      to screen gives opportunity to use tuberculosis services in AIDS control and ART
      scaling-up programmes.

PMID- 17002732
TI  - Domestic violence during pregnancy and risk of low birthweight and maternal
      complications: a prospective cohort study at Mulago Hospital, Uganda.
AB  - OBJECTIVES: To investigate whether domestic violence during pregnancy is a risk
      factor for antepartum hospitalization or low birthweight (LBW) delivery. METHODS:
      A prospective cohort study was conducted in Mulago hospital, Kampala, Uganda,
      among 612 women recruited in the second pregnancy trimester and followed up to
      delivery, from May 2004 through July 2005. The exposure (physical, sexual or
      psychological violence during pregnancy) was assessed using the Abuse Assessment
      Screen. The relative and attributable risks of LBW and antepartum hospitalization
      were estimated using multivariate logistic regression analysis. RESULTS: The 169
      women [27.7% 95% CI (24.3-31.5%)] who reported domestic violence during pregnancy
      did not differ significantly from the unexposed regarding sociodemographic
      characteristics, but differed significantly (P < 0.05) regarding domicile
      variables (had less household decision-making power, more resided in extended
      families and more had unplanned pregnancy). They delivered babies with a mean
      birthweight 2647.5 +/- 604 g, on average 186 g [(95% CI 76-296); P = 0.001] lower
      than those unexposed. After adjusting for age, parity, number of living children,
      pregnancy planning, domicile and number of years in marriage, the relative risk
      (RR) of LBW delivery among women exposed to domestic violence was 3.78 (95% CI
      2.86-5.00). Such women had a 37% higher risk of obstetric complications (such as
      hypertension, premature rupture of membranes and anaemia) that necessitated
      antepartum hospitalization [RR 1.37 (95% CI 1.01-1.84)]. CONCLUSION: In this
      pregnancy cohort, domestic violence during pregnancy was a risk factor for LBW
      delivery and antepartum hospitalization.

PMID- 17002733
TI  - Could the Chagas disease elimination programme in Venezuela be compromised by
      reinvasion of houses by sylvatic Rhodnius prolixus bug populations?
AB  - The Andean Pact Initiative (1997) committed Andean countries to eliminate
      vectorial transmission of Chagas disease by 2010 via widespread residual
      insecticide spraying. In Venezuela, this aim could be compromised by reinvasion
      of houses by palm tree populations of the major vector Rhodnius prolixus. To test
      this hypothesis, a multivariate logistic regression was undertaken of risk
      factors for triatomine infestation and colonization in 552 houses and 1068 peri
      domestic outbuildings in Barinas State. After adjusting for other risk factors,
      including palm roofs, R. prolixus infestation and colonization of outbuildings
      (and, to some extent, houses) was significantly associated with proximity to high
      densities of Attalea butyracea palm trees. House infestation and/or colonization
      was also positively associated with bug density in peri-domestic outbuildings,
      the presence of pigsties and nests. Hence, R. prolixus populations in
      ineffectively sprayed outbuildings could also provide an important source of
      house re-infestations. The secondary vector Triatoma maculata was mainly found
      associated with the presence of hens nesting both indoors and outdoors.

PMID- 17002734
TI  - Impact of a communication programme on female genital cutting in eastern Nigeria.
AB  - OBJECTIVES: This study describes a female genital cutting (FGC) elimination
      communication programme in Enugu State and assesses its impact in changing
      relevant knowledge, attitudes and behavioural intentions. METHODS: The FGC
      programme combined a community mobilization component with targeted advocacy and
      mass media activities. Data for assessing the impact of the programme derived
      from baseline and follow-up surveys in three intervention local government areas
      (LGA) in Enugu State and three comparison LGAs in Ebonyi State. An ideation model
      of behaviour change guided the analyses of the impact of the programme on
      personal advocacy for FGC, perceived self-efficacy to refuse pressure to perform
      FGC, perceived social support for FGC discontinuation, perceived benefits of FGC,
      perceived health complications of FGC and intention not to perform FGC on
      daughters. The analytical methods include comparing change in pertinent outcome
      variables from baseline to follow-up in the two study states and using logistic
      regression on follow-up data for the intervention state to assess the link
      between programme exposure and the relevant outcome indicators. RESULTS: The data
      show that while the pertinent ideational factors and the intention not to perform
      FGC either worsened or remained stagnant in Ebonyi State, they improved
      significantly in Enugu State. The logistic regression results show that programme
      exposure is associated with the expected improvements in all the pertinent
      indicators. CONCLUSION: The multimedia communication programme has been effective
      in changing FGC-related attitudes and promoting the intention not to perform FGC.

PMID- 17002735
TI  - Colombia and Cuba, contrasting models in Latin America's health sector reform.
AB  - Latin American national health systems were drastically overhauled by the health
      sector reforms the 1990s. Governments were urged by donors and by the
      international financial institutions to make major institutional changes,
      including the separation of purchaser and provider functions and privatization.
      This article first analyses a striking paradox of the far-reaching reform
      measures: contrary to what is imposed on public health services, after
      privatization purchaser and provider functions are reunited. Then we compare two
      contrasting examples: Colombia, which is internationally promoted as a successful
      -and radical--example of 'market-oriented' health care reform, and Cuba, which
      followed a highly 'conservative' path to adapt its public system to the new
      conditions since the 1990s, going against the model of the international
      institutions. The Colombian reform has not been able to materialize its promises
      of universality, improved equity, efficiency and better quality, while Cuban
      health care remains free, accessible for everybody and of good quality. Finally,
      we argue that the basic premises of the ongoing health sector reforms in Latin
      America are not based on the people's needs, but are strongly influenced by the
      needs of foreign--especially North American--corporations. However, an
      alternative model of health sector reform, such as the Cuban one, can probably
      not be pursued without fundamental changes in the economic and political
      foundations of Latin American societies.

PMID- 17002736
TI  - Local terminology for medicines to treat fever in Bougouni District, Mali:
      implications for the introduction and evaluation of malaria treatment policies.
AB  - OBJECTIVE: To explore Bambara language terminology and classification for locally
      available antimicrobial medicines in order to better target promotional messages
      and improve evaluation measures in Bougouni District, Mali. METHODS: Mothers (n =
      20) and drug vendors (n = 15) were asked to freelist medicines used to treat
      childhood illnesses, and to identify all medicines that corresponded to each of
      the listed terms from an array of medicines displayed with their packaging.
      RESULTS: Each Bambara language medicine term can refer to numerous modern
      medicines, and each modern medicine has several Bambara names. The term nivakini
      (Nivaquine), often translated as 'chloroquine', refers to a wide range of
      medicines commonly used to treat malaria, many with no antimalarial effect.
      Antibiotics were also identified as common treatments for malaria. Mothers and
      vendors used slightly different terminology when discussing treatments for
      malaria, and sometimes employed the same term to refer to different medicines.
      Neither mothers nor vendors clearly differentiated between antimalarial
      medicines. Colour, shape and packaging play a large role in their recognition,
      classification and use. CONCLUSIONS: Current household survey methods are likely
      to provide inaccurate estimates of appropriate treatment of febrile illness, and
      thus alternative approaches are recommended. In introducing new malaria
      treatments, malaria control programmes should differentiate recommended
      treatments from other medications through distinctive packaging, drug appearance
      and appropriate Bambara language terms.

PMID- 17002737
TI  - Dental attrition models predicting temporomandibular joint disease or masticatory
      muscle pain versus asymptomatic controls.
AB  - AIMS: To determine whether patients with temporomandibular joint disease or
      masticatory muscle pain can be usefully differentiated from asymptomatic controls
      using multifactorial classification tree models of attrition severity and/or
      rates. METHODS: Measures of attrition severity and rates in patients diagnosed
      with disc displacement (n = 52), osteoarthrosis (n = 74), or masticatory muscle
      pain only (n = 43) were compared against those in asymptomatic controls (n =
      132). Cross-validated classification tree models were tested for fit with
      sensitivity, specificity, accuracy and log likelihood accountability. RESULTS:
      The model for identifying asymptomatic controls only required the three measures
      of attrition severity (anterior, mediotrusive and laterotrusive posterior) to be
      differentiated from the patients with a 74.2 +/- 3.8% cross-validation accuracy.
      This compared with cross-validation accuracies of 69.7 +/- 3.7% for
      differentiating disc displacement using anterior and laterotrusive attrition
      severity, 68.7 +/- 3.9% for differentiating disc displacement using anterior and
      laterotrusive attrition rates, 70.9 +/- 3.3% for differentiating osteoarthrosis
      using anterior attrition severity and rates, 94.6 +/- 2.1% for differentiating
      myofascial pain using mediotrusive and laterotrusive attrition severity, and 92.0
      +/- 2.1% for differentiating myofascial pain using mediotrusive and anterior
      attrition rates. The myofascial pain models exceeded the > or =75% sensitivity
      and > or =90% specificity thresholds recommended for diagnostic tests, and the
      asymptomatic control model approached these thresholds. CONCLUSION:
      Multifactorial models using attrition severity and rates may differentiate
      masticatory muscle pain patients from asymptomatic controls, and have some
      predictive value for differentiating intracapsular temporomandibular disorder
      patients as well.

PMID- 17002738
TI  - Relationship between tooth contacts in the retruded contact position and
      mandibular positioning during retrusion.
AB  - We conducted a series of studies with the purpose to investigate the locations of
      tooth contacts in the retruded contact position (RCP) and to discuss their
      significance in the stomatognathic system. In the present study, the relationship
      between the locations of RCP contacts and mandibular positioning during retrusion
      was examined. Thirty dentists and clinical residents were selected as subjects.
      One specialist in prosthetic dentistry examined each subject for the location of
      the RCP contacts. The mandibular positioning during retrusion was measured using
      a mandibular movement analysis system with six degrees of freedom. Originally
      programmed software was developed. Five reference points were selected: the
      central lower incisor (point I), the first molars on both sides (points RM and
      LM) and the condyles on both sides (points RC and LC). Tooth contact was observed
      most frequently at the second molar, followed by the first premolar. Points I, RM
      and LM all moved in an inferior-posterior direction, whereas points RC and LC
      moved in various directions ranging from superior-posterior to inferior
      posterior. When the subjects were divided into two groups according to the most
      anterior tooth of occlusion in the RCP, the condylar positioning tended to be
      more superior in the group with molar contact than that with premolar contact.
      These results suggest that the locations of RCP contacts could be an important
      factor in jaw guidance during retrusion.

PMID- 17002739
TI  - Reproducibility of jaw movements in patients with craniomandibular disorders.
AB  - It has never been investigated, if mandibular movements of patients with
      craniomandibular disorders (CMD) result in a lower reproducibility of dynamic
      functional parameters which are used for the individual articulator setting. The
      aim of the present study was to compare the reproducibility of electronically
      registered functional parameters in patients with CMD and in a control group.
      Dynamic functional parameters were recorded in 30 patients and 30 volunteers with
      a computerized ultrasound system (ARCUSdigma). The whole registration was
      performed three times during one session and three times at a second session 1
      week later. The horizontal condylar inclination in the patient group gave a
      standard deviation of 2.17 degrees +/- 0.95 degrees , indicating poorer
      reproducibility than in the volunteer group, for which the standard deviation was
      1.37 degrees +/- 0.42 degrees . The reproducibility of measurements of the
      Bennett angle was also poorer in the patient group than in the volunteer group,
      with standard deviations of 1.70 degrees +/- 0.62 degrees and 1.22 degrees +/-
      0.40 degrees , respectively. The standard deviations calculated for determination
      of incisal inclination during laterotrusion was 3.02 degrees +/- 1.49 degrees for
      patients and 2.30 degrees +/- 1.17 degrees for volunteers. The standard
      deviations for incisal inclination during protrusion was 2.02 degrees +/- 0.95
      degrees for patients and 2.06 degrees +/- 1.82 degrees for volunteers. The
      reproducibility of measurement of horizontal condylar inclination, Bennett angle
      and incisal inclination during laterotrusion therefore showed significantly lower
      reproducibility in the patient group than in the volunteer group (P < 0.05). The
      overall reproducibility of the measurements was nevertheless good in both groups,
      with standard deviations under 3.1 degrees , so that an individual setting of an
      articulator seems useful even in patients with CMD.

PMID- 17002740
TI  - A pilot study of quantitative assessment of mandible advancement using pressure
      flow relationship during midazolam sedation.
AB  - It has been proposed that a titration of the mandibular positioner would be a
      promising method for predicting the outcome of nasal continuous positive airway
      pressure (CPAP) therapy. This study was carried out to test the hypothesis that
      mandible advancement could be evaluated by analysis of inspiratory flow
      limitation using a titration procedure. To explore its effect, we examined upper
      airway pressure-flow relationships using a titrated mandible positioner during
      midazolam sedation. Non-flow limited inspiration occurred when the mandible was
      advanced 7.1 +/- 1.2 mm from centric occlusion position. In the centric occlusion
      position (0 mm advancement), Pcrit was -1.9 +/- 2.9 cmH2O and Rua was 23.3 +/-
      4.5 cmH2O L(-1) s(-1). In the eMAP position, Pcrit was -7.3 +/- 1.9 cmH2O and Rua
      was 27.8 +/- 3.3 cmH2O L(-1) s(-1). Essentially no CPAP was required to overcome
      flow limitation in eMAP position, whereas 3.7 +/- 2.2 cmH2O CPAP was required in
      centric occlusion position. We conclude that assessing inspiratory flow
      limitation using a titrated mandible positioner was effective for estimating
      individual-matched mandible positions.

PMID- 17002741
TI  - Preliminary study on the effect of oral care on recovery from surgery in elderly
      patients.
AB  - This study aimed to clarify the effectiveness of post-operative oral care,
      including tooth brushing, denture cleaning and tongue cleaning, after digestive
      tract surgery. Subjects included 30 elderly patients aged 60-98 years (74.9 +/-
      7.8 years) who underwent digestive tract surgery. Subjects were randomly divided
      into an intervention group and a control group. In the intervention group, the
      following oral care was provided daily over a 5-min period in the morning
      starting at baseline (day of surgery) and continued for 5 days: gargling with
      povidone iodine, tooth brushing, denture cleaning using a special brush and
      tongue cleaning using a tongue brush. In the control group, the subjects only
      gargled with povidone iodine. We compared the following variables between the two
      groups at baseline and 5 days later: the sensation of dry mouth, intra-oral gas
      concentration, pulmonary sounds, body temperature and bacterial flora. The number
      of patients with abnormal pulmonary sounds (dry or moist rales) increased from 1
      to 2 in the intervention group and from 0 to 4 in the control group (P < 0.05).
      The average number of bacterial species per subject for the control group was
      3.64 +/- 1.34 pre-operatively and 3.50 +/- 1.74 post-operatively, whereas that
      for the intervention group was 3.08 +/- 0.95 pre-operatively and 2.62 +/- 0.65
      post-operatively. In the intervention group, there was a significant decrease in
      the number of bacterial species (P < 0.05). These findings indicate that post
      operative oral care in elderly patients undergoing digestive tract surgery lowers
      the number of bacterial species found in the oral cavity. This effect, in turn,
      might improve respiratory function.

PMID- 17002742
TI  - Fracture load and marginal fit of shrinkage-free ZrSiO4 all-ceramic crowns after
      chewing simulation.
AB  - The aim of this in vitro study was to evaluate the fracture load and marginal
      accuracy of crowns made from a shrinkage-free ZrSiO4 ceramic cemented with glass
      ionomer or composite cement after chewing simulation. Thirty-two human mandibular
      molars were randomly divided into two groups. All teeth were prepared for and
      restored with shrinkage-free ZrSiO4 ceramic crowns (Everest HPC, KaVo). The
      crowns of group A (N = 16) were luted to the teeth using KetacCem and group B (N
      = 16) were adhesively cemented using Panavia21EX. Measurements of the marginal
      accuracy before and after cementation were made using replicas and an image
      analysis system. All specimens were exposed to 1.2 million cycles of thermo
      mechanical fatigue in a chewing simulator. Surviving specimens were subsequently
      loaded until fracture in a static testing device. Fracture loads (N) were
      recorded. All specimens survived chewing simulation. The mean fracture loads (+/
      s.d.) were Group A, 1622 N (+/-433); group B, 1957 N (+/-806). There was no
      significant difference between the two groups (P > 0.05). The marginal gap values
      before cementation were (mean +/- s.d.): Group A, 32.7 microm (+/-6.8); group B,
      33.0 microm (+/-6.7). The mean marginal gap values after cementation were (+/
      s.d.): Group A, 44.6 microm (+/-6.7); group B, 46.6 microm (+/-7.7). The marginal
      openings were significantly higher after cementation for both groups (P < 0.05).
      All test groups demonstrated fracture load and marginal accuracy values within
      the range of clinical acceptability.

PMID- 17002743
TI  - Prosthetic complications in fixed endosseous implant-borne reconstructions after
      an observations period of at least 40 months.
AB  - One hundred and seventy-two fixed reconstructions (317 prosthetic units), made on
      283 ITI implants in 105 patients (age range 25-86 years) with a minimum follow-up
      period of 40 months, were taken into the study to analyse technical complication
      rate, complication type and costs for repair. The mean evaluation time was 62.5
      +/- 25.3 months. Eighty were single crowns and 92 different types of fixed
      partial dentures (FPDs). In 45 cases the construction was screw retained and in
      127 cases cemented with zinc phosphate cement or an acrylic-based cement.
      Complications occurred after a minimum period of 2 months and a maximum period of
      100 months (mean: 35.9 +/- 21.4 months). Fifty-five prosthetic interventions were
      needed on 44 constructions (25%) of which 88% in the molar/premolar region. The
      lowest percentage of complications occurred in single crowns (25%), the highest
      in 3-4 unit FPDs (35%) and in FPDs with an extension (44%). Of the necessary
      clinical repair, 36% was recementing and 38% tightening the screws. Of all
      interventions, 14% were classified as minor (no treatment or <10 min chair time),
      70% as moderate (>10 min but <60 min chair time) and 14% as major interventions
      (>60 min and additional costs for replacement of parts and/or laboratory). For
      seven patients the additional costs ranged from euro 28 to euro 840. Bruxing
      seemed to play a significant role in the frequency of complications. Longer
      constructions seemed to be more prone to complications. The relatively high
      occurrence of technical complications should be discussed with the patient before
      the start of the treatment.

PMID- 17002744
TI  - The regulation of masticatory function and food bolus formation.
AB  - This review emphasizes the following points: 1. The values of the physiological
      parameters of mastication (number of cycles and total electromyographic activity
      in the sequence, sequence duration, cycle frequency in the sequence, kinetic
      characteristics of the cycles) are characteristic of each individual and vary
      widely from one individual to another. In a given individual their modification
      reflects an adaptation of mastication to the size of the food bolus, and the
      hardness and rheological characteristics of the food. 2. The ready-to-swallow
      food boluses produced by different individuals nevertheless display similar
      particle size distributions. 3. Ageing entails adaptation of the masticatory
      function and does not impair swallowing. 4. Observed increase in total
      electromyographic activity shows that more energy is expended in mastication by
      full denture wearers. Despite this increased muscle activity, loss of teeth, even
      if compensated for by complete dentures, hinders the formation of a normal bolus.
      The food boluses made by denture wearers thus contain many large-size particles.
      The impaired mastication observed in denture wearers approaches the masticatory
      disabilities found in persons with neuromotor deficiencies.

PMID- 17002745
TI  - A review of the shortened dental arch concept focusing on the work by the
      Kayser/Nijmegen group.
AB  - The aims of this paper were to review the literature on shortened dental arches
      with special focus on publications of the Kayser/Nijmegen group, and to evaluate
      the discussions on the shortened dental arch concept found in the literature. A
      MEDLINE (PubMed) search was conducted for articles in English published in the
      dental literature from 1966 to November 2005. The search revealed
      epidemiological, cross-sectional and longitudinal clinical studies as well as
      opinion papers, the majority of which were published by the Dutch group. The
      studies found in general no clinically significant differences between subjects
      with shortened dental arches of three to five occlusal units and complete dental
      arches regarding variables such as masticatory ability, signs and symptoms of
      temporomandibular disorders, migration of remaining teeth, periodontal support,
      and oral comfort. The findings from cross-sectional studies were corroborated
      longitudinally. No systematic clinical study with conflicting results was found.
      The shortened dental arch concept was accepted by a great majority of dentists
      but not widely practised. The studies reviewed showed that shortened dental
      arches comprising anterior and premolar teeth in general fulfil the requirements
      of a functional dentition. It may therefore be concluded that the concept
      deserves serious consideration in treatment planning for partially edentulous
      patients. However, with ongoing changes, e.g. in dental health and economy, the
      concept requires continuing research, evaluation and discussion. Patients' needs
      and demands vary much and should be individually assessed but the shortened
      dental arch concept deserves to be included in all treatment planning for
      partially edentulous patients.

PMID- 17002746
TI  - Prosthetic rehabilitation of a midfacial defect resulting from lethal midline
      granuloma--a clinical report.
AB  - Prosthetic rehabilitation of the midfacial defects has always perplexed
      maxillofacial prosthodontists. These midfacial defects lead to functional and
      cosmetic deficiencies. One of the causes of such defects is midline lethal
      granuloma, which is a destructive granulomatous lesion of uncertain aetiology,
      involving the nose, paranasal sinuses and the palate. Presented here is a
      clinical report of a 22-year-old male patient diagnosed to have lethal midline
      granuloma, who was referred to the Department of Prosthodontics, SDM College of
      Dental Sciences Dharwad. The patient had a severe midfacial defect involving the
      nose, the paranasal sinuses, the palate and the soft tissues of the face.
      Although the lesion was not of the rapidly progressive type at the time of
      rehabilitation, the non-specific inflammatory process was persisting. The patient
      was treated with chemotherapy and palliative therapy. The primary objective of
      the prosthetic rehabilitation was to provide closure of the severe defect to
      protect the soft tissues from environmental exposure. Secondarily the prosthesis
      also provided acceptable aesthetics and psychological benefit to the patient.

PMID- 17002747
TI  - The conundrum of conservation education and the conservation mission.

PMID- 17002748
TI  - Professional capacity building: the missing agenda in conservation priority
      setting.

PMID- 17002750
TI  - Bighorn sheep, mountain lions, and the ethics of conservation.

PMID- 17002751
TI  - From is to should: helping students translate conservation biology into
      conservation policy.

PMID- 17002752
TI  - Evidence for the role of infectious disease in species extinction and
      endangerment.
AB  - Infectious disease is listed among the top five causes of global species
      extinctions. However, the majority of available data supporting this contention
      is largely anecdotal. We used the IUCN Red List of Threatened and Endangered
      Species and literature indexed in the ISI Web of Science to assess the role of
      infectious disease in global species loss. Infectious disease was listed as a
      contributing factor in <4% of species extinctions known to have occurred since
      1500 (833 plants and animals) and as contributing to a species' status as
      critically endangered in <8% of cases (2,852 critically endangered plants and
      animals). Although infectious diseases appear to play a minor role in global
      species loss, our findings underscore two important limitations in the available
      evidence: uncertainty surrounding the threats to species survival and a temporal
      bias in the data. Several initiatives could help overcome these obstacles,
      including rigorous scientific tests to determine which infectious diseases
      present a significant threat at the species level, recognition of the limitations
      associated with the lack of baseline data for the role of infectious disease in
      species extinctions, combining data with theory to discern the circumstances
      under which infectious disease is most likely to serve as an agent of extinction,
      and improving surveillance programs for the detection of infectious disease. An
      evidence-based understanding of the role of infectious disease in species
      extinction and endangerment will help prioritize conservation initiatives and
      protect global biodiversity.

PMID- 17002753
TI  - The complex links between governance and biodiversity.
AB  - We argue that two problems weaken the claims of those who link corruption and the
      exploitation of natural resources. The first is conceptual and the second is
      methodological. Studies that use national-level indicators of corruption fail to
      note that corruption comes in many forms, at multiple levels, that may affect
      resource use quite differently: negatively, positively, or not at all. Without a
      clear causal model of the mechanism by which corruption affects resources, one
      should treat with caution any estimated relationship between corruption and the
      state of natural resources. Simple, atheoretical models linking corruption
      measures and natural resource use typically do not account for other important
      control variables pivotal to the relationship between humans and natural
      resources. By way of illustration of these two general concerns, we used
      statistical methods to demonstrate that the findings of a recent, well-known
      study that posits a link between corruption and decreases in forests and
      elephants are not robust to simple conceptual and methodological refinements. In
      particular, once we controlled for a few plausible anthropogenic and biophysical
      conditioning factors, estimated the effects in changes rather than levels so as
      not to confound cross-sectional and longitudinal variation, and incorporated
      additional observations from the same data sources, corruption levels no longer
      had any explanatory power.

PMID- 17002754
TI  - Conservation as virtue: a scientific and social process for conservation ethics.
AB  - Most scientists take ethical arguments for conservation as given and focus on
      scientific or economic questions. Although nature conservation is often
      considered a just cause, it is given little further consideration. A lack of
      attention to ethical theory raises serious concerns for how conservation
      scientists conceive and practice ethics. I contrast two common ways scientists
      approach ethics, as demonstrated in the writings of Stephen Jay Gould and E. O.
      Wilson. Gould casts severe doubt as to whether any ethics are possible from
      science, whereas Wilson proposes science as the only path to ethics. I argue
      these two methods ultimately limit popular support for conservation and offer
      Alasdair MacIntyre's "virtue ethics" as an alternative. Unlike Gould and Wilson,
      MacIntyre provides an ethical theory that reconciles scientific inquiry and
      social traditions. Recent studies of the Civil Rights Movement in the United
      States affirm MacIntyre's claims and provide important insights for conservation
      today. These accounts argue that social solidarity and political success against
      segregation were possible only as rooted in the particular language, logic, and
      practices of a robust cultural tradition. If correct, conservation science should
      attend to several questions. On what basis can conservation achieve widespread
      cultural legitimacy? What are the particular social currencies for a conservation
      ethic? What role does science play in such a scheme? MacIntyre's careful
      positioning of scientific and social traditions provides a hopeful ethical
      direction for conservation.

PMID- 17002756
TI  - The normative dimension and legal meaning of endangered and recovery in the U.S.
      Endangered Species Act.
AB  - The ethical, legal, and social significance of the U.S. Endangered Species Act of
      1973 (ESA) is widely appreciated. Much of the significance of the act arises from
      the legal definitions that the act provides for the terms threatened species and
      endangered species. The meanings of these terms are important because they give
      legal meaning to the concept of a recovered species. Unfortunately, the meanings
      of these terms are often misapprehended and rarely subjected to formal analysis.
      We analyzed the legal meaning of recovered species and illustrate key points with
      details from "recovery" efforts for the gray wolf (Canis lupus). We focused on
      interpreting the phrase "significant portion of its range," which is part of the
      legal definition of endangered species. We argue that recovery and endangerment
      entail a fundamentally normative dimension (i.e., specifying conditions of
      endangerment) and a fundamentally scientific dimension (i.e., determining whether
      a species meets the conditions of endangerment). Specifying conditions for
      endangerment is largely normative because it judges risks of extinction to be
      either acceptable or unacceptable. Like many other laws that specify what is
      unacceptable, the ESA largely specifies the conditions that constitute
      unacceptable extinction risk. The ESA specifies unacceptable risks of extinction
      by defining endangered species in terms of the portion of a species' range over
      which a species is "in danger of extinction." Our analysis indicated that (1)
      legal recovery entails much more than the scientific notion of population
      viability, (2) most efforts to recover endangered species are grossly inadequate,
      and (3) many unlisted species meet the legal definition of an endangered or
      threatened species.

PMID- 17002755
TI  - Achieving integrative, collaborative ecosystem management.
AB  - Although numerous principles have been identified as being important for
      successfully integrating social and ecological factors in collaborative
      management, few authors have illustrated how these principles are used and why
      they are effective. On the basis of a review of the ecosystem management and
      collaboration literature, we identified eight factors important for integrative,
      collaborative ecosystem management-integrated and balanced goals, inclusive
      public involvement, stakeholder influence, consensus group approach,
      collaborative stewardship, monitoring and adaptive management, multidisciplinary
      data, and economic incentives.We examined four cases of successful ecosystem
      management to illustrate how the factors were incorporated and discuss the role
      they played in each case's success. The cases illustrate that balancing social
      and ecosystem sustainability goals is possible. Collaborative efforts resulted in
      part from factors aimed at making plans economically feasible and from meaningful
      stakeholder participation in ongoing management. It also required participation
      in monitoring programs to ensure stakeholder interests were protected and
      management efforts were focused on agreed-upon goals. Data collection efforts
      were not all-inclusive and systematic; rather, they addressed the ecological,
      economic, and social aspects of key issues as they emerged over time. Economic
      considerations appear to be broader than simply providing economic incentives;
      stakeholders seem willing to trade some economic value for recreational or
      environmental benefits. The cases demonstrate that it is not idealistic to
      believe integrative, collaborative ecosystem management is possible in field
      applications.

PMID- 17002757
TI  - Collaborating to conserve large mammals in Southeast Asia.
AB  - Depressed mammal densities characterize the interior of many Southeast Asian
      protected areas, and are the result of commercial and subsistence hunting. Local
      people are part of this problem but can participate in solutions through improved
      partnerships that incorporate local knowledge into problem diagnosis. The process
      of involving local people helps build a constituency that is more aware of its
      role (positive and negative) in a protected area and generates site-specific
      conservation assessments for management planning. We illustrate the practical
      details of initiating such a partnership through our work in a Thai wildlife
      sanctuary. Many protected areas in Southeast Asia present similar opportunities.
      In local workshops, village woodsmen were led through ranking exercises to
      develop a spatially explicit picture of 20-year trends in the abundance of 31
      mammal species and to compare species-specific causes for declines. Within five
      taxonomic groups, leaf monkeys (primates), porcupines (rodents), tigers (large
      carnivores), civets (small carnivores), and elephants (ungulates) had declined
      most severely (37-74%). Commercial hunting contributed heavily to extensive
      population declines for most species, and subsistence hunting was locally
      significant for some small carnivores, leaf monkeys, and deer. Workshops thus
      clarified which species were at highest risk of local extinction, where the most
      threatened populations were, and causes for these patterns. Most important, they
      advanced a shared problem definition, thereby unlocking opportunities for
      collaboration. As a result, local people and sanctuary managers have increased
      communication, initiated joint monitoring and patrolling, and established
      wildlife recovery zones. Using local knowledge has limitations, but the process
      of engaging local people promotes collaborative action that large mammals in
      Southeast Asia need.

PMID- 17002758
TI  - The impact of increased environmental stochasticity due to climate change on the
      dynamics of asiatic wild ass.
AB  - Theory proposes that increased environmental stochasticity negatively impacts
      population viability. Thus, in addition to the directional changes predicted for
      weather parameters under global climate change (GCC), the increase in variance of
      these parameters may also have a negative effect on biodiversity. As a case
      study, we assessed the impact of interannual variance in precipitation on the
      viability of an Asiatic wild ass (Equus hemionus) population reintroduced in
      Makhtesh Ramon Nature Reserve, Israel. We monitored the population from 1985 to
      1999 to determine what environmental factors affect reproductive success. Annual
      precipitation during the year before conception, drought conditions during
      gestation, and population size determined reproductive success. We used the
      parameters derived from this model to assess population performance under various
      scenarios in a Leslie matrix type model with demographic and environmental
      stochasticity. Specifically, we used a change in the precipitation regime in our
      study area to formulate a GCC scenario and compared the simulated dynamics of the
      population with a no-change scenario. The coefficient of variation in population
      size under the global change scenario was 30% higher than under the no-change
      scenario. Minor die-offs (> or = 15%) following droughts increased extinction
      probability nearly 10-fold. Our results support the idea that an increase in
      environmental stochasticity due to GCC may, in itself, pose a significant threat
      to biodiversity.

PMID- 17002759
TI  - Effects of selective logging on bat communities in the southeastern Amazon.
AB  - Although extensive areas of tropical forest are selectively logged each year, the
      responses of bat communities to this form of disturbance have rarely been
      examined. Our objectives were to (1) compare bat abundance, species composition,
      and feeding guild structure between unlogged and low-intensity selectively logged
      (1-4 logged stems/ha) sampling grids in the southeastern Amazon and (2) examine
      correlations between logging-induced changes in bat communities and forest
      structure. We captured bats in understory and canopy mist nets set in five 1-ha
      study grids in both logged and unlogged forest. We captured 996 individuals,
      representing 5 families, 32 genera, and 49 species. Abundances of nectarivorous
      and frugivorous taxa (Glossophaginae, Lonchophyllinae, Stenodermatinae, and
      Carolliinae) were higher at logged sites, where canopy openness and understory
      foliage density were greatest. In contrast, insectivorous and omnivorous species
      (Emballonuridae, Mormoopidae, Phyllostominae, and Vespertilionidae) were more
      abundant in unlogged sites, where canopy foliage density and variability in the
      understory stratum were greatest. Multivariate analyses indicated that understory
      bat species composition differed strongly between logged and unlogged sites but
      provided little evidence of logging effects for the canopy fauna. Different
      responses among feeding guilds and taxonomic groups appeared to be related to
      foraging and echolocation strategies and to changes in canopy cover and
      understory foliage densities. Our results suggest that even low-intensity logging
      modifies habitat structure, leading to changes in bat species composition.

PMID- 17002760
TI  - A comparison of landscapes occupied by increasing and decreasing populations of
      grassland birds.
AB  - For several decades, many grassland bird species have been declining in abundance
      throughout the Midwest and Great Plains regions of the United States, possibly
      due to loss of natural grassland habitat and increasing urbanization. I used 20
      years of data from the North American Breeding Bird Survey to identify
      increasing, decreasing, and stable populations of 36 grassland-nesting bird
      species. I characterized the immediate landscape (circle with radius = 30 km)
      surrounding each population based on data from the National Resources Inventory.
      For each landscape, I calculated the proportion of eight different land-cover
      types: restored grassland, rangeland, cultivated cropland, pasture, noncultivated
      cropland, forest, urban land, and water. Using a null model, I compared landscape
      composition of increasing, decreasing, and stable populations. As predicted on
      the basis of the habitat preferences of grassland birds, increasing populations
      inhabited landscapes that contained significantly more restored grassland and
      rangeland but significantly less forest land and urban land than landscapes
      inhabited by decreasing populations. There was no significant difference in the
      proportion of cropland within the landscapes of increasing and decreasing
      populations, although cropland composed a large proportion (>30%) of many
      landscapes. In contrast, restored grassland typically composed a very small
      proportion (<3.5%) of total land cover, yet it was significantly more common in
      the landscapes of increasing than decreasing populations. These results suggest
      that grassland birds may benefit from government initiatives, such as the
      Conservation Reserve Program, that promote the restoration of grassland at a
      landscape scale.

PMID- 17002761
TI  - Assessing habitat quality for a migratory songbird wintering in natural and
      agricultural habitats.
AB  - As tropical forests are cleared, a greater proportion of migratory songbirds are
      forced to winter in agricultural and disturbed habitats, which, if poorer in
      quality than natural forests, could contribute to population declines. We
      compared demographic indicators of habitat quality for a focal species, the
      American Redstart (Setophaga ruticilla), wintering in Jamaican citrus orchards
      and shade coffee plantations with those in four natural habitats: mangrove,
      coastal scrub, coastal palm, and dry limestone forests. Demographic measures of
      habitat quality included density, age and sex ratio, apparent survival, and
      changes in body mass. Measures of habitat quality for redstarts in citrus and
      coffee habitats were generally intermediate between the highest (mangrove) and
      lowest (dry limestone) measurements from natural habitats. The decline in mean
      body mass over the winter period was a strong predictor of annual survival rate
      among habitats, and we suggest that measures of body condition coupled with
      survival data provide the best measures of habitat quality for nonbreeding
      songbirds. Density, which is far easier to estimate, was correlated with these
      more labor-intensive measures, particularly in the late winter when food is
      likely most limiting. Thus, local density may be useful as an approximation of
      habitat quality for wintering migrant warblers. Our findings bolster those of
      previous studies based on bird abundance that suggest arboreal agricultural
      habitats in the tropics can be useful for the conservation of generalist,
      insectivorous birds, including many migratory passerines such as redstarts.

PMID- 17002762
TI  - Conservation value of clustered housing developments.
AB  - Traditionally, exurban lands in Colorado have been subdivided into a grid of
      parcels ranging from 2 to 16 ha. From an ecological perspective, this dispersed
      pattern of development effectively maximizes the individual influence of each
      home on the land. Clustered housing developments, designed to maximize open
      space, are assumed to benefit plant and wildlife communities of conservation
      interest. They have become a popular alternative for rural development despite
      the lack of empirical evidence demonstrating their conservation benefits. To
      better inform rural land-use planning, we evaluated clustered housing
      developments by comparing their spatial pattern with that of dispersed housing
      developments and by comparing their conservation value with that of both
      dispersed housing developments and undeveloped areas in Boulder County, Colorado.
      We used four indicators to assess conservation value: (1) densities of songbirds,
      (2) nest density and survival of ground-nesting birds, (3) presence of mammals,
      and (4) percent cover and proportion of native and non-native plant species.
      Clustered and dispersed housing developments did not differ on the majority of
      variables we examined. Both types of housing development had significantly higher
      densities of non-native and human-commensal species and significantly lower
      densities of native and human-sensitive species than undeveloped areas. More
      rigorous ecological guidelines and planning on a regional scale may help create
      clustered developments with higher conservation value.

PMID- 17002763
TI  - Remarkable amphibian biomass and abundance in an isolated wetland: implications
      for wetland conservation.
AB  - Despite the continuing loss of wetland habitats and associated declines in
      amphibian populations, attempts to translate wetland losses into measurable
      losses to ecosystems have been lacking. We estimated the potential productivity
      from the amphibian community that would be compromised by the loss of a single
      isolated wetland that has been protected from most industrial, agricultural, and
      urban impacts for the past 54 years. We used a continuous drift fence at Ellenton
      Bay, a 10-ha freshwater wetland on the Savannah River Site, near Aiken, South
      Carolina (U.S.A.), to sample all amphibians for 1 year following a prolonged
      drought. Despite intensive agricultural use of the land surrounding Ellenton Bay
      prior to 1951, we documented 24 species and remarkably high numbers and biomass
      of juvenile amphibians (>360,000 individuals; >1,400 kg) produced during one
      breeding season. Anurans (17 species) were more abundant than salamanders (7
      species), comprising 96.4% of individual captures. Most (95.9%) of the amphibian
      biomass came from 232095 individuals of a single species of anuran (southern
      leopard frog[Rana sphenocephala]). Our results revealed the resilience of an
      amphibian community to natural stressors and historical habitat alteration and
      the potential magnitude of biomass and energy transfer from isolated wetlands to
      surrounding terrestrial habitat. We attributed the postdrought success of
      amphibians to a combination of adult longevity (often >5 years), a reduction in
      predator abundance, and an abundance of larval food resources. Likewise, the
      increase of forest cover around Ellenton Bay from <20% in 1951 to >60% in 2001
      probably contributed to the long-term persistence of amphibians at this site. Our
      findings provide an optimistic counterpoint to the issue of the global decline of
      biological diversity by demonstrating that conservation efforts can mitigate
      historical habitat degradation.

PMID- 17002764
TI  - Incorporation of recreational fishing effort into design of marine protected
      areas.
AB  - Theoretical models of marine protected areas (MPAs) that explore benefits to
      fisheries or biodiversity conservation often assume a dynamic pool of fishing
      effort. For instance, effort is homogenously distributed over areas from which
      subsets of reserves are chosen. I tested this and other model assumptions with a
      case study of the multiple-use Jervis Bay Marine Park. Prior to zoning of the
      park I conducted 166 surveys of the park's recreational fisheries, plotting the
      location of 16,009 anglers. I converted these plots into diagrams of fishing
      effort and analyzed correlates between fishing and habitat and the effect of two
      reserve designs-the draft and final zoning plans of the park-on the 15 fisheries
      observed. Fisheries were strongly correlated with particular habitats and had
      negatively skewed and often bimodal spatial distribution. The second mode of
      intensely fished habitat could be 6 SD greater than the fishery's mean allocation
      of effort by area. In the draft-zoning plan, sanctuary zone (no-take) area and
      potential subduction of fishing effort were similar. In the final plan, which was
      altered in response to public comment, the area of sanctuary zone increased, and
      the impact on fishing effort decreased. In only one case was a fishery's most
      intensely targeted location closed to fishing. Because of the discriminating
      manner with which fishers target habitats, if simple percentage targets are used
      for planning, sanctuary location can be adjusted to avoid existing fishing
      effort. According to modeled outcomes, the implication of this may be diminished
      reserve effectiveness. To address this, reserve area should be implicitly linked
      to subducted fishing effort when promoting or modeling MPAs.

PMID- 17002765
TI  - Mortality gradients within and among dominant plant populations as barometers of
      ecosystem change during extreme drought.
AB  - Understanding patterns of plant population mortality during extreme weather
      events is important to conservation planners because the frequency of such events
      is expected to increase, creating the need to integrate climatic uncertainty into
      management. Dominant plants provide habitat and ecosystem structure, so changes
      in their distribution can be expected to have cascading effects on entire
      communities. Observing areas that respond quickly to climate fluctuations
      provides foresight into future ecological changes and will help prioritize
      conservation efforts. We investigated patterns of mortality in six dominant plant
      species during a drought in the southwestern United States. We quantified
      population mortality for each species across its regional distribution and tested
      hypotheses to identify ecological stress gradients for each species. Our results
      revealed three major patterns: (1) dominant species from diverse habitat types
      (i.e., riparian, chaparral, and low- to high-elevation forests) exhibited
      significant mortality, indicating that the effects of drought were widespread;
      (2) average mortality differed among dominant species (one-seed juniper[Juniperus
      monosperma (Engelm.) Sarg.] 3.3%; manzanita[Arctostaphylos pungens Kunth], 14.6%;
      quaking aspen[Populus tremuloides Michx.], 15.4%; ponderosa pine[Pinus ponderosa
      P. & C. Lawson], 15.9%; Fremont cottonwood[Populus fremontii S. Wats.], 20.7%;
      and pinyon pine[Pinus edulis Engelm.], 41.4%); (3) all dominant species showed
      localized patterns of very high mortality (24-100%) consistent with water stress
      gradients. Land managers should plan for climatic uncertainty by promoting tree
      recruitment in rare habitat types, alleviating unnatural levels of competition on
      dominant plants, and conserving sites across water stress gradients. High-stress
      sites, such as those we examined, have conservation value as barometers of change
      and because they may harbor genotypes that are adapted to climatic extremes.

PMID- 17002766
TI  - Planting history and propagule pressure as predictors of invasion by woody
      species in a temperate region.
AB  - We studied 28 alien tree species currently planted for forestry purposes in the
      Czech Republic to determine the probability of their escape from cultivation and
      naturalization. Indicators of propagule pressure (number of administrative units
      in which a species is planted and total planting area) and time of introduction
      into cultivation were used as explanatory variables in multiple regression
      models. Fourteen species escaped from cultivation, and 39% of the variance was
      explained by the number of planting units and the time of introduction, the
      latter being more important. Species introduced early had a higher probability of
      escape than those introduced later, with more than 95% probability of escape for
      those introduced before 1801 and <5% for those introduced after 1892. Probability
      of naturalization was more difficult to predict, and eight species were
      misclassified. A model omitting two species with the largest influence on the
      model yielded similar predictors of naturalization as did the probability of
      escape. Both phases of invasion therefore appear to be driven by planting and
      introduction history in a similar way. Our results demonstrate the importance of
      forestry for recruitment of invasive trees. Six alien forestry trees, classified
      as invasive in the Czech Republic, are currently reported in nature reserves. In
      addition, forestry authorities want to increase the diversity of alien species
      and planting area in the country.

PMID- 17002767
TI  - Using scalar models for precautionary assessments of threatened species.
AB  - Scalar population models, commonly referred to as count-based models, are based
      on time-series data of population sizes and may be useful for screening-level
      ecological risk assessments when data for more complex models are not available.
      Appropriate use of such models for management purposes, however, requires
      understanding inherent biases that may exist in these models. Through a series of
      simulations, which compared predictions of risk of decline of scalar and matrix
      based models, we examined whether discrepancies may arise from different dynamics
      displayed due to age structure and generation time. We also examined scalar and
      matrix-based population models of 18 real populations for potential patterns of
      bias in population viability estimates. In the simulation study, precautionary
      bias (i.e., overestimating risks of decline) of scalar models increased as a
      function of generation time. Models of real populations showed poor fit between
      scalar and matrix-based models, with scalar models predicting significantly
      higher risks of decline on average. The strength of this bias was not correlated
      with generation time, suggesting that additional sources of bias may be masking
      this relationship. Scalar models can be useful for screening-level assessments,
      which should in general be precautionary, but the potential shortfalls of these
      models should be considered before using them as a basis for management
      decisions.

PMID- 17002768
TI  - A mechanistic approach to evaluation of umbrella species as conservation
      surrogates.
AB  - Although species with large area requirements are sometimes used as umbrella
      species, their general utility as conservation tools is uncertain. We surveyed
      the species diversity of birds, butterflies, carabids, and forest-floor plants in
      forest sites across an area (1,600 km2) in which we delineated large breeding
      home ranges of Northern Goshawk (Accipiter gentilis). We tested whether
      protection of the home ranges could serve as an effective umbrella to protect
      sympatric species of the four taxa. We also used an empirical habitat model of
      occupancy of home range to examine mechanisms by which the Northern Goshawk acts
      as an umbrella species. Among species richness, abundance, and species
      composition of the four taxa, only abundance and species composition of birds
      differed between sites located inside and outside home ranges, which was due to
      greater abundance of bird species that were prey of Northern Goshawks inside the
      home ranges. Thus, although home range indicated areas with high abundance of
      certain bird prey species, it was not effective as an indicator of the species
      diversity of all four taxa. We also did not find any difference in species
      richness, abundance, and species composition between sites predicted as occupied
      and unoccupied using the habitat model. In contrast, when we selected sites on
      the basis of each habitat variable in the model, habitat variables that selected
      sites either in agricultural or forested landscapes encompassed sites with high
      species richness or particular species composition. This result suggests that the
      low performance of the Northern Goshawk as an umbrella species is due to this
      species' preference for habitat in both agricultural and forested landscapes.
      Species that can adjust to changes in habitat conditions may not act as effective
      umbrella species despite having large home ranges.

PMID- 17002769
TI  - Understanding barriers to implementation of an adaptive land management program.
AB  - The Florida Fish and Wildlife Conservation Commission manages over 650,000 ha,
      including 26 wildlife management and environmental areas. To improve management,
      they developed an objective-based vegetation management (OBVM) process that
      focuses on desired conditions of plant communities through an adaptive management
      framework. Our goals were to understand potential barriers to implementing OBVM
      and to recommend strategies to overcome barriers. A literature review identified
      47 potential barriers in six categories to implementation of adaptive and
      ecosystem management: logistical, communication, attitudinal, institutional,
      conceptual, and educational. We explored these barriers through a bureau-wide
      survey of 90 staff involved in OBVM and personal interviews with area managers,
      scientists, and administrators. The survey incorporated an organizational culture
      assessment instrument to gauge how institutional factors might influence OBVM
      implementation. The survey response rate was 69%. Logistics and communications
      were the greatest barriers to implementing OBVM. Respondents perceived that the
      agency had inadequate resources for implementing OBVM and provided inadequate
      information. About one-third of the respondents believed OBVM would decrease
      their job flexibility and perceived greater institutional barriers to the
      approach. The 43% of respondents who believed they would have more responsibility
      under OBVM also had greater attitudinal barriers. A similar percentage of
      respondents reported OBVM would not give enough priority to wildlife. Staff
      believed that current agency culture was hierarchical but preferred a culture
      that would provide more flexibility for adaptive management and would foster
      learning from land management activities. In light of the barriers to OBVM, we
      recommend the following: (1) mitigation of logistical barriers by addressing real
      and perceived constraints of staff, funds, and other resources in a participatory
      manner; (2) mitigation of communication barriers through interpersonal and
      electronic communication channels; (3) development of an OBVM external advisory
      committee; and (4) adoption of characteristics of an organizational culture that
      promotes flexibility and learning.

PMID- 17002770
TI  - Testing hypotheses for the success of different conservation strategies.
AB  - Evaluations of the success of different conservation strategies are still in
      their infancy. We used four different measures of project outcomes--ecological,
      economic, attitudinal, and behavioral--to test hypotheses derived from the
      assumptions that underlie contemporary conservation solutions. Our hypotheses
      concerned the effects of natural resource utilization, market integration,
      decentralization, and community homogeneity on project success. We reviewed the
      conservation and development literature and used a specific protocol to extract
      and code the information in a sample of papers. Although our results are by no
      means conclusive and suffer from the paucity of high-quality data and independent
      monitoring (80% of the original sample of 124 projects provided inadequate
      information for use in this study), they show that permitted use of natural
      resources, market access, and greater community involvement in the conservation
      project are all important factors for a successful outcome. Without better
      monitoring schemes in place, it is still impossible to provide a systematic
      evaluation of how different strategies are best suited to different conservation
      challenges.

PMID- 17002771
TI  - Impact of criticism of null-hypothesis significance testing on statistical
      reporting practices in conservation biology.
AB  - Over the last decade, criticisms of null-hypothesis significance testing have
      grown dramatically, and several alternative practices, such as confidence
      intervals, information theoretic, and Bayesian methods, have been advocated. Have
      these calls for change had an impact on the statistical reporting practices in
      conservation biology? In 2000 and 2001, 92% of sampled articles in Conservation
      Biology and Biological Conservation reported results of null-hypothesis tests. In
      2005 this figure dropped to 78%. There were corresponding increases in the use of
      confidence intervals, information theoretic, and Bayesian techniques. Of those
      articles reporting null-hypothesis testing--which still easily constitute the
      majority--very few report statistical power (8%) and many misinterpret
      statistical nonsignificance as evidence for no effect (63%). Overall, results of
      our survey show some improvements in statistical practice, but further efforts
      are clearly required to move the discipline toward improved practices.

PMID- 17002772
TI  - Species discovery versus species identification in DNA barcoding efforts:
      response to Rubinoff.

PMID- 17002773
TI  - DNA barcoding evolves into the familiar.

PMID- 17002774
TI  - How conservation scientists can help develop social capital for biodiversity.

PMID- 17002775
TI  - Smallholders, the Amazon's new conservationists.

PMID- 17002780
TI  - Cryptotrichosporon anacardii gen. nov., sp. nov., a new trichosporonoid capsulate
      basidiomycetous yeast from Nigeria that is able to form melanin on niger seed
      agar.
AB  - Five yeast isolates obtained from cashew tree flowers in Nigeria resembled
      Cryptococcus neoformans phenotypically by producing brown pigmented colonies on
      niger seed agar, expressing a capsule, and being able to grow at 37 degrees C.
      However, rRNA gene sequences, including the 18S rRNA gene, the D1/D2 domains of
      the 26S rRNA gene and the ITS1+2 regions, suggested that these yeasts form a
      basal lineage within the Trichosporonales (Tremellomycetidae, Hymenomycetes,
      Basidiomycota, Fungi). Since the isolates could not be identified with any known
      genus and species within the Trichosporonales, we describe them as
      Cryptotrichosporon anacardii gen. et sp. nov. with CBS 9551(T) (=NRRL Y-27671) as
      the type strain. The taxonomic conflict between phenetic and molecular
      classification schemes within this group of fungi is discussed, and is resolved
      in favor of the latter.

PMID- 17002781
TI  - Two new species of Kazachstania that form ascospores connected by a belt-like
      intersporal body: Kazachstania zonata and Kazachstania gamospora.
AB  - Four strains of ascomycetous yeasts were isolated from samples collected at two
      locations in southern Japan. The strains formed two warty ascospores that were
      joined together by an intersporal body appearing as a belt. Phylogenetic analysis
      of rRNA gene nucleotide sequences indicated that the strains represented two new
      and closely related species of the genus Kazachstania. Isolates of one of the
      species were from Miyazaki Prefecture and those of the other species were from
      the Iriomote Islands. Genetic separation of the two species was further confirmed
      by DNA-DNA reassociation, which gave values of 63.3-78.1%, and from interspecific
      crosses, which gave nonviable ascospores. On the basis of these data, the
      isolates from Miyazaki Prefecture are described as Kazachstania zonata sp. nov.
      [type strain NBRC 100504=CBS 10326, mating types NBRC 101821 (+), NBRC 101822 (
      )], and the isolates from the Iriomote Islands are described as Kazachstania
      gamospora sp. nov. [type strain NBRC 11056=CBS 10328, mating types NBRC 101825
      (+), NBRC 101826 (-)].

PMID- 17002782
TI  - The YCR079w gene confers a rapamycin-resistant function and encodes the sixth
      type 2C protein phosphatase in Saccharomyces cerevisiae.
AB  - Type 2C protein phosphatase (PP2C) is a monomeric enzyme and requires Mg(2+) or
      Mn(2+) for its activity. Up to now, seven PP2C-like genes have been identified in
      the genome of Saccharomyces cerevisiae. However, the protein encoded by the sixth
      PP2C-like gene, YCR079w, has not been demonstrated to have PP2C activity. In this
      study, we show that YCR079w confers a rapamycin-resistant function in yeast
      cells, and we also demonstrate that the YCR079w-encoded protein exhibits
      characteristics of a typical PP2C. Therefore, YCR079w encodes the sixth PP2C,
      PTC6, in budding yeast.

PMID- 17002783
TI  - Clonal variation in Xenorhabdus nematophila virulence and suppression of Manduca
      sexta immunity.
AB  - Virulence of the insect pathogen Xenorhabdus nematophila is attributed in part to
      its ability to suppress immunity. For example, X. nematophila suppresses
      transcripts encoding several antimicrobial proteins, even in the presence of
      Salmonella enterica, an inducer of these transcripts. We show here that virulence
      and immune suppression phenotypes can be lost in a subpopulation of X.
      nematophila. Cells that have undergone 'virulence modulation' (vmo) have
      attenuated virulence and fail to suppress antimicrobial transcript levels,
      haemocyte aggregation and nodulation in Manduca sexta insects. When plated on
      certain media, vmo cells have a higher proportion of translucent (versus opaque)
      colonies compared with non-vmo cells. Like vmo strains, translucent colony
      isolates are defective in virulence and immune suppression. The X. nematophila
      genome encodes two 'opacity' genes with similarity to the Ail/PagC/Rck family of
      outer membrane proteins involved in adherence, invasion and serum resistance.
      Quantitative polymerase chain reaction analysis shows that RNA levels of one of
      these opacity genes, opaB, are higher in opaque relative to translucent colonies.
      We propose that in X. nematophila opaB may be one of several factors involved in
      immune suppression during infection, and expression of these factors can be co
      ordinately eliminated in a subpopulation, possibly through a phase variation
      mechanism.

PMID- 17002784
TI  - Pertussis toxin transiently affects barrier integrity, organelle organization and
      transmigration of monocytes in a human brain microvascular endothelial cell
      barrier model.
AB  - Encephalopathies and neurological disorders are sometimes associated with
      respiratory tract infections caused by Bordetella pertussis. For these
      complications to occur cerebral barriers have to be compromised. Therefore, the
      influence of pertussis toxin (PT), a decisive virulence determinant of B.
      pertussis, on endothelial barrier integrity was investigated. Human brain
      microvascular endothelial cells cultured on Transwell filter devices were used as
      model for the blood brain barrier. PT, but not its B-oligomer, induced a
      reduction of the transendothelial resistance and enhanced the permeability for
      the protein marker horseradish peroxidase. Moreover, transmigration of human
      monocytes was also elevated suggesting a PT-associated enhancement of the
      diapedesis of blood leucocytes. Uptake and trafficking of PT was followed by
      electron microscopy via clathrin-coated pits and accumulation in lysosomes and
      microvesicular bodies. The breach in barrier integrity was accompanied by a
      transient disintegration of Golgi structures. Interestingly, PT-induced effects
      were only transient and restoration of barrier function was observed after 24 h.
      In summary, intoxication by PT causes a transient destruction of the cellular
      organization in human brain-derived endothelial cells resulting in a transient
      disruption of barrier functions. We suggest that these findings reflect early
      steps in the development of neurological disorders associated with pertussis
      disease.

PMID- 17002785
TI  - Highly purified lipopolysaccharides from Burkholderia cepacia complex clinical
      isolates induce inflammatory cytokine responses via TLR4-mediated MAPK signalling
      pathways and activation of NFkappaB.
AB  - In cystic fibrosis (CF), bacteria of the Burkholderia cepacia complex (Bcc) can
      induce a fulminant inflammation with pneumonitis and sepsis. Lipopolysaccharide
      (LPS) may be an important virulence factor associated with this decline but
      little is known about the molecular pathogenesis of Bcc LPS. In this study we
      have investigated the inflammatory response to highly purified LPS from different
      Bcc clinical isolates and the cellular signalling pathways employed. The
      inflammatory response (TNFalpha, IL-6) was measured in human MonoMac 6 monocytes
      and inhibition experiments were used to investigate the Toll-like receptors and
      associated adaptor molecules and pathways utilized. LPS from all clinical Bcc
      isolates induced significant pro-inflammatory cytokines and utilized TLR4 and
      CD14 to mediate activation of mitogen-activated protein kinase pathways, IkappaB
      alpha degradation and NFkappaB activation. However, LPS from different clinical
      isolates of the same clonal strain of Burkholderia cenocepacia were found to
      induce a varied inflammatory response. LPS from clinical isolates of Burkholderia
      multivorans was found to activate the inflammatory response via MyD88-independent
      pathways. This study suggests that LPS alone from clinical isolates of Bcc is an
      important virulence factor in CF and utilizes TLR4-mediated signalling pathways
      to induce a significant inflammatory response.

PMID- 17002786
TI  - A knowledge, attitudes, and practice survey among obstetrician-gynaecologists on
      intimate partner violence in Flanders, Belgium.
AB  - BACKGROUND: Intimate partner violence (IPV) has consistently been found to
      afflict one in twenty pregnant women and is therefore considered a leading cause
      of physical injury, mental illness and adverse pregnancy outcome. A general
      antenatal screening policy has been advocated, though compliance with such
      guidelines tends to be low. We therefore attempted to identify potential barriers
      to IPV screening in a context where no guidelines have been instigated yet.
      METHODS: Questionnaire-based Knowledge, Attitude, and Practice survey among
      obstetrician-gynaecologists in Flanders, Belgium (n = 478). RESULTS: The response
      rate was 52.1% (249/478). Gynaecologists prove rather unfamiliar with IPV and
      therefore largely underestimate the extent of the problem. Merely 6.8% (17/249)
      of the respondents ever received or pursued any kind of education on IPV.
      Accordingly they do feel insufficiently skilled to deal with IPV, yet
      sufficiently capable of recognizing IPV among their patients. Survey participants
      largely refute the incentive of universal screening in favour of opportunistic
      screening and do not consider pregnancy as a window of opportunity for routine
      screening. They do consider screening for IPV as an issue of medical liability
      and therefore do not suffer from a lack of motivation to screen. In addition,
      obstetrician-gynaecologists do believe that screening for IPV may be an effective
      means to counteract abusive behaviours. Yet, their outcome expectancy is weighed
      down by their perceived lack of self-efficacy in dealing with IPV, by lack of
      familiarity with referral procedures and by their perceived lack of available
      referral services. Major external or patient-related barriers to IPV screening
      included a perceived lack of time and fear of offending or insulting patients.
      Overall, merely 8.4 % (21/245) of gynaecologists in this survey performed some
      kind of IPV questioning on a regular basis. Finally, physician education was
      found to be the strongest predictor of a positive attitude towards screening and
      of current screening practices. CONCLUSION: Endorsement of physician training on
      IPV is an important first step towards successful implementation of screening
      guidelines for IPV. Additional introduction of enabling and reinforcement
      strategies such as screening tools, patient leaflets, formal referral pathways,
      and physician feedback may further enhance compliance with screening
      recommendations and guidelines.

PMID- 17002787
TI  - Identification of novel candidate target genes in amplicons of Glioblastoma
      multiforme tumors detected by expression and CGH microarray profiling.
AB  - BACKGROUND: Conventional cytogenetic and comparative genomic hybridization (CGH)
      studies in brain malignancies have shown that glioblastoma multiforme (GBM) is
      characterized by complex structural and numerical alterations. However, the
      limited resolution of these techniques has precluded the precise identification
      of detailed specific gene copy number alterations. RESULTS: We performed a genome
      wide survey of gene copy number changes in 20 primary GBMs by CGH on cDNA
      microarrays. A novel amplicon at 4p15, and previously uncharacterized amplicons
      at 13q32-34 and 1q32 were detected and are analyzed here. These amplicons
      contained amplified genes not previously reported. Other amplified regions
      containing well-known oncogenes in GBMs were also detected at 7p12 (EGFR), 7q21
      (CDK6), 4q12 (PDGFRA), and 12q13-15 (MDM2 and CDK4). In order to identify the
      putative target genes of the amplifications, and to determine the changes in gene
      expression levels associated with copy number change events, we carried out
      parallel gene expression profiling analyses using the same cDNA microarrays. We
      detected overexpression of the novel amplified genes SLA/LP and STIM2 (4p15), and
      TNFSF13B and COL4A2 (13q32-34). Some of the candidate target genes of
      amplification (EGFR, CDK6, MDM2, CDK4, and TNFSF13B) were tested in an
      independent set of 111 primary GBMs by using FISH and immunohistological assays.
      The novel candidate 13q-amplification target TNFSF13B was amplified in 8% of the
      tumors, and showed protein expression in 20% of the GBMs. CONCLUSION: This high
      resolution analysis allowed us to propose novel candidate target genes such as
      STIM2 at 4p15, and TNFSF13B or COL4A2 at 13q32-34 that could potentially
      contribute to the pathogenesis of these tumors and which would require futher
      investigations. We showed that overexpression of the amplified genes could be
      attributable to gene dosage and speculate that deregulation of those genes could
      be important in the development and progression of GBM. Our findings highlight
      the important influence in GBM of signaling pathways such as the PI3K/AKT,
      consistent with the invasive features of this tumor.

PMID- 17002788
TI  - Translating microarray data for diagnostic testing in childhood leukaemia.
AB  - BACKGROUND: Recent findings from microarray studies have raised the prospect of a
      standardized diagnostic gene expression platform to enhance accurate diagnosis
      and risk stratification in paediatric acute lymphoblastic leukaemia (ALL).
      However, the robustness as well as the format for such a diagnostic test remains
      to be determined. As a step towards clinical application of these findings, we
      have systematically analyzed a published ALL microarray data set using Robust
      Multi-array Analysis (RMA) and Random Forest (RF). METHODS: We examined published
      microarray data from 104 ALL patients specimens, that represent six different
      subgroups defined by cytogenetic features and immunophenotypes. Using the
      decision-tree based supervised learning algorithm Random Forest (RF), we
      determined a small set of genes for optimal subgroup distinction and subsequently
      validated their predictive power in an independent patient cohort. RESULTS: We
      achieved very high overall ALL subgroup prediction accuracies of about 98%, and
      were able to verify the robustness of these genes in an independent panel of 68
      specimens obtained from a different institution and processed in a different
      laboratory. Our study established that the selection of discriminating genes is
      strongly dependent on the analysis method. This may have profound implications
      for clinical use, particularly when the classifier is reduced to a small set of
      genes. We have demonstrated that as few as 26 genes yield accurate class
      prediction and importantly, almost 70% of these genes have not been previously
      identified as essential for class distinction of the six ALL subgroups.
      CONCLUSION: Our finding supports the feasibility of qRT-PCR technology for
      standardized diagnostic testing in paediatric ALL and should, in conjunction with
      conventional cytogenetics lead to a more accurate classification of the disease.
      In addition, we have demonstrated that microarray findings from one study can be
      confirmed in an independent study, using an entirely independent patient cohort
      and with microarray experiments being performed by a different research team.

PMID- 17002789
TI  - Seeding of epithelial cells into circulation during surgery for breast cancer:
      the fate of malignant and benign mobilized cells.
AB  - BACKGROUND: Surgery of malignant tumors has long been suspected to be the reason
      for enhancement of growth of metastases with fatal outcome. This often prevented
      surgeons from touching the tumor if not absolutely necessary. We have shown in
      lung cancer patients that surgery, itself, leads to mobilization of tumor cells
      into peripheral blood. Some of the mobilized cells finding an appropriate niche
      might grow to form early metastases. Monitoring of tumor cell release during and
      the fate of such cells after surgery for breast cancer may help to reveal how
      metastases develop after surgery. METHOD: We used the MAINTRAC analysis, a new
      tool for online observation of circulating epithelial cells, to monitor the
      number of epithelial cells before, 30 min, 60 min, three and seven days after
      surgery and during subsequent variable follow up in breast cancer patients.
      RESULTS: Circulating epithelial cells were already present before surgery in all
      patients. During the first 30-60 min after surgery values did not change
      immediately. They started increasing during the following 3 to 4 days up to
      thousand fold in 85% of treated patients in spite of complete resection of the
      tumor with tumor free margins in all patients. There was a subsequent re
      decrease, with cell numbers remaining above pre-surgery values in 58% of cases
      until onset of chemotherapy. In a few cases, where no further therapy or only
      hormone treatment was given due to low risk stage, cell numbers were monitored
      for up to three years. They remained elevated with no or a slow decrease over
      time. This was in contrast to the observation in a patient where surgery was
      performed for benign condition. She was monitored before surgery with no cells
      detectable. Epithelial cells increased up to more than 50,000 after surgery but
      followed by a complete reduction to below the threshold of detection. CONCLUSION:
      Frequently before but regularly during surgery of breast cancer, epithelial cells
      are mobilized into circulation. Part of these cells, most probably normal or
      apoptotic cells, are cleared from the circulation as also shown to occur in
      benign conditions. After resection even if complete and of small tumors, cells
      can remain in the circulation over long times. Such cells may remain "dormant"
      but might settle and grow into metastases, if they find appropriate conditions,
      even after years.

PMID- 17002790
TI  - Comparative sequence analysis reveals an intricate network among REST, CREB and
      miRNA in mediating neuronal gene expression.
AB  - BACKGROUND: Two distinct classes of regulators have been implicated in regulating
      neuronal gene expression and mediating neuronal identity: transcription factors
      such as REST/NRSF (RE1 silencing transcription factor) and CREB (cAMP response
      element-binding protein), and microRNAs (miRNAs). How these two classes of
      regulators act together to mediate neuronal gene expression is unclear. RESULTS:
      Using comparative sequence analysis, here we report the identification of 895
      sites (NRSE) as the putative targets of REST. A set of the identified NRSE sites
      is present in the vicinity of the miRNA genes that are specifically expressed in
      brain-related tissues, suggesting the transcriptional regulation of these miRNAs
      by REST. We have further identified target genes of these miRNAs, and discovered
      that REST and its cofactor complex are targets of multiple brain-related miRNAs
      including miR-124a, miR-9 and miR-132. Given the role of both REST and miRNA as
      repressors, these findings point to a double-negative feedback loop between REST
      and the miRNAs in stabilizing and maintaining neuronal gene expression.
      Additionally, we find that the brain-related miRNA genes are highly enriched with
      evolutionarily conserved cAMP response elements (CRE) in their regulatory
      regions, implicating the role of CREB in the positive regulation of these miRNAs.
      CONCLUSION: The expression of neuronal genes and neuronal identity are controlled
      by multiple factors, including transcriptional regulation through REST and post
      transcriptional modification by several brain-related miRNAs. We demonstrate that
      these different levels of regulation are coordinated through extensive feedbacks,
      and propose a network among REST, CREB proteins and the brain-related miRNAs as a
      robust program for mediating neuronal gene expression.

PMID- 17002791
TI  - Mode of delivery and cord blood cytokines: a birth cohort study.
AB  - BACKGROUND: The mechanisms for the association between birth by cesarean section
      and atopy and asthma are largely unknown. OBJECTIVE: To examine whether cesarean
      section results in neonatal secretion of cytokines that are associated with
      increased risk of atopy and/or asthma in childhood. To examine whether the
      association between mode of delivery and neonatal immune responses is explained
      by exposure to the maternal gut flora (a marker of the vaginal flora). METHODS:
      CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN
      gamma, and IL-10 (at baseline and after stimulation with antigens [dust mite and
      cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified
      by ELISA. Total and specific microbes were quantified in maternal stool. The
      relation between mode of delivery and cord blood cytokines was examined by linear
      regression. The relation between maternal stool microbes and cord blood cytokines
      was examined by Spearman's correlation coefficients. RESULTS: Cesarean section
      was associated with increased levels of IL-13 and IFN-gamma. In multivariate
      analyses, cesarean section was associated with an increment of 79.4 pg/ml in
      secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P <
      0.001). Among children born by vaginal delivery, gram-positive anaerobes and
      total anaerobes in maternal stool were positively correlated with levels of IL
      10, and gram-negative aerobic bacteria in maternal stool were negatively
      correlated with levels of IL-13 and IFN-gamma. CONCLUSION: Cesarean section is
      associated with increased levels of IL-13 and IFN-gamma, perhaps because of lack
      of labor and/or reduced exposure to specific microbes (e.g., gram-positive
      anaerobes) at birth.

PMID- 17002792
TI  - Systemic inflammatory response syndrome in adult patients with nosocomial
      bloodstream infections due to enterococci.
AB  - BACKGROUND: Enterococci are the third leading cause of nosocomial bloodstream
      infection (BSI). Vancomycin resistant enterococci are common and provide
      treatment challenges; however questions remain about VRE's pathogenicity and its
      direct clinical impact. This study analyzed the inflammatory response of
      Enterococcal BSI, contrasting infections from vancomycin-resistant and vancomycin
      susceptible isolates. METHODS: We performed a historical cohort study on 50
      adults with enterococcal BSI to evaluate the associated systemic inflammatory
      response syndrome (SIRS) and mortality. We examined SIRS scores 2 days prior
      through 14 days after the first positive blood culture. Vancomycin resistant (n =
      17) and susceptible infections (n = 33) were compared. Variables significant in
      univariate analysis were entered into a logistic regression model to determine
      the affect on mortality. RESULTS: 60% of BSI were caused by E. faecalis and 34%
      by E. faecium. 34% of the isolates were vancomycin resistant. Mean APACHE II (A2)
      score on the day of BSI was 16. Appropriate antimicrobials were begun within 24
      hours in 52%. Septic shock occurred in 62% and severe sepsis in an additional
      18%. Incidence of organ failure was as follows: respiratory 42%, renal 48%,
      hematologic 44%, hepatic 26%. Crude mortality was 48%. Progression to septic
      shock was associated with death (OR 14.9, p < .001). There was no difference in
      A2 scores on days -2, -1 and 0 between the VRE and VSE groups. Maximal SIR
      (severe sepsis, septic shock or death) was seen on day 2 for VSE BSI vs. day 8
      for VRE. No significant difference was noted in the incidence of organ failure, 7
      day or overall mortality between the two groups. Univariate analysis revealed
      that AP2>18 at BSI onset, and respiratory, cardiovascular, renal, hematologic and
      hepatic failure were associated with death, but time to appropriate therapy >24
      hours, age, and infection due to VRE were not. Multivariate analysis revealed
      that hematologic (OR 8.4, p = .025) and cardiovascular failure (OR 7.5, p = 032)
      independently predicted death. CONCLUSION: In patients with enterococcal BSI, (1)
      the incidence of septic shock and organ failure is high, (2) patients with VRE
      BSI are not more acutely ill prior to infection than those with VSE BSI, and (3)
      the development of hematologic or cardiovascular failure independently predicts
      death.

PMID- 17002793
TI  - Evidence for chronic, peripheral activation of neutrophils in polyarticular
      juvenile rheumatoid arthritis.
AB  - Although strong epidemiologic evidence suggests an important role for adaptive
      immunity in the pathogenesis of polyarticular juvenile rheumatoid arthritis
      (JRA), there remain many aspects of the disease that suggest equally important
      contributions of the innate immune system. We used gene expression arrays and
      computer modeling to examine the function in neutrophils of 25 children with
      polyarticular JRA. Computer analysis identified 712 genes that were
      differentially expressed between patients and healthy controls. Computer-assisted
      analysis of the differentially expressed genes demonstrated functional
      connections linked to both interleukin (IL)-8- and interferon-gamma (IFN-gamma)
      regulated processes. Of special note is that the gene expression fingerprint of
      children with active JRA remained essentially unchanged even after they had
      responded to therapy. This result differed markedly from our previously reported
      work, in which gene expression profiles in buffy coats of children with
      polyarticular JRA reverted to normal after disease control was achieved
      pharmacologically. These findings suggest that JRA neutrophils remain in an
      activated state even during disease quiescence. Computer modeling of array data
      further demonstrated disruption of gene regulatory networks in clusters of genes
      modulated by IFN-gamma and IL-8. These cytokines have previously been shown to
      independently regulate the frequency (IFN-gamma) and amplitude (IL-8) of the
      oscillations of key metabolites in neutrophils, including nicotinamide adenine
      dinucleotide (phosphate) (NAD(P)H) and superoxide ion. Using real-time, high
      speed, single-cell photoimaging, we observed that 6/6 JRA patients displayed a
      characteristic defect in 12% to 23% of the neutrophils tested. Reagents known to
      induce only frequency fluctuations of NAD(P)H and superoxide ion induced both
      frequency and amplitude fluctuations in JRA neutrophils. This is a novel finding
      that was observed in children with both active (n = 4) and inactive (n = 2) JRA.
      A subpopulation of polyarticular JRA neutrophils are in a chronic, activated
      state, a state that persists when the disease is well controlled
      pharmacologically. Furthermore, polyarticular JRA neutrophils exhibit an
      intrinsic defect in the regulation of metabolic oscillations and superoxide ion
      production. Our data are consistent with the hypothesis that neutrophils play an
      essential role in the pathogenesis of polyarticular JRA.

PMID- 17002794
TI  - Septic shock is correlated with asymmetrical dimethyl arginine levels, which may
      be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II
      gene: a prospective observational study.
AB  - INTRODUCTION: Asymmetrical dimethyl arginine (ADMA) is an endogenous non
      selective inhibitor of nitric oxide synthase that may influence the severity of
      organ failure and the occurrence of shock secondary to an infectious insult.
      Levels may be genetically determined by a promoter polymorphism in a regulatory
      gene encoding dimethylarginine dimethylaminohydrolase II (DDAH II), which
      functions by metabolising ADMA to citrulline. The aim of this study was to
      examine the association between ADMA levels and the severity of organ failure and
      shock in severe sepsis and also to assess the influence of a promoter
      polymorphism in DDAH II on ADMA levels. METHODS: A prospective observational
      study was designed, and 47 intensive care unit (ICU) patients with severe sepsis
      and 10 healthy controls were enrolled. Serum ADMA and IL-6 were assayed on
      admission to the ICU and seven days later. Allelic variation for a polymorphism
      at position -449 in the DDAH II gene was assessed in each patient. Clinical and
      demographic details were also collected. RESULTS: On day 1 more ADMA was
      detectable in the ICU group than in the control group (p = 0.005). Levels
      subsequently increased during the first week in ICU (p = 0.001). ADMA levels were
      associated with vasopressor requirements on day one (p = 0.001). ADMA levels and
      Sequential Organ Failure Assessment scores were directly associated on day one (p
      = 0.0001) and day seven (p = 0.002). The degree of acidaemia and lactaemia was
      directly correlated with ADMA levels at both time points (p < 0.01). On day
      seven, IL-6 was directly correlated with ADMA levels (p = 0.006). The variant
      allele with G at position -449 in the DDAH II gene was associated with increased
      ADMA concentrations at both time points (p < 0.05). CONCLUSION: Severity of organ
      failure, inflammation and presence of early shock in severe sepsis are associated
      with increased ADMA levels. ADMA concentrations may be influenced by a
      polymorphism in the DDAH II gene.

PMID- 17002795
TI  - Anemia, transfusion, and phlebotomy practices in critically ill patients with
      prolonged ICU length of stay: a cohort study.
AB  - INTRODUCTION: Anemia among the critically ill has been described in patients with
      short to medium length of stay (LOS) in the intensive care unit (ICU), but it has
      not been described in long-stay ICU patients. This study was performed to
      characterize anemia, transfusion, and phlebotomy practices in patients with
      prolonged ICU LOS. METHODS: We conducted a retrospective chart review of
      consecutive patients admitted to a medical-surgical ICU in a tertiary care
      university hospital over three years; patients included had a continuous LOS in
      the ICU of 30 days or longer. Information on transfusion, phlebotomy, and
      outcomes were collected daily from days 22 to 112 of the ICU stay. RESULTS: A
      total of 155 patients were enrolled. The mean age, admission Acute Physiology and
      Chronic Health Evaluation II score, and median ICU LOS were 62.3 +/- 16.3 years,
      23 +/- 8, and 49 days (interquartile range 36-70 days), respectively. Mean
      hemoglobin remained stable at 9.4 +/- 1.4 g/dl from day 7 onward. Mean daily
      phlebotomy volume was 13.3 +/- 7.3 ml, and 62% of patients received a mean of 3.4
      +/- 5.3 units of packed red blood cells at a mean hemoglobin trigger of 7.7 +/-
      0.9 g/dl after day 21. Transfused patients had significantly greater acuity of
      illness, phlebotomy volumes, ICU LOS and mortality, and had a lower hemoglobin
      than did those who were not transfused. Multivariate logistic regression analysis
      identified the following as independently associated with the likelihood of
      requiring transfusion in nonbleeding patients: baseline hemoglobin, daily
      phlebotomy volume, ICU LOS, and erythropoietin therapy (used almost exclusively
      in dialysis dependent renal failure in this cohort of patients). Small increases
      in average phlebotomy (3.5 ml/day, 95% confidence interval 2.4-6.8 ml/day) were
      associated with a doubling in the odds of being transfused after day 21.
      CONCLUSION: Anemia, phlebotomy, and transfusions, despite low hemoglobin
      triggers, are common in ICU patients long after admission. Small decreases in
      phlebotomy volume are associated with significantly reduced transfusion
      requirements in patients with prolonged ICU LOS.

PMID- 17002796
TI  - Randomised trials relevant to mental health conducted in low and middle-income
      countries: protocol for a survey of studies published in 1991, 1995 and 2000 and
      assessment of their relevance.
AB  - BACKGROUND: A substantial proportion of the psychiatric burden of disease falls
      on the world's poorest nations. Despite this, relatively little is known about
      the quality and content of clinical research undertaken in these countries, or
      the relevance of the interventions evaluated and specifically that of randomised
      trials. This project aims to survey the content, quality and accessibility of a
      sample of trials relevant to mental health conducted within low and middle-income
      countries; to compare these with studies conducted in high-income countries; and
      to assess their relevance for the needs of low and middle-income countries.
      METHODS: An extensive search for all trials, or possible trials, published in
      1991, 1995 and 2000 with participants in low and middle-income countries has
      already been conducted. Studies evaluating prevention or treatment of a mental
      health problem within these three years will be identified and further searches
      conducted to assess completeness of the initial search. Data on study quality and
      characteristics will be extracted from each report. Accessibility will be
      estimated based on whether each citation is available on MEDLINE. Trials relevant
      to schizophrenia will be compared with a random sample of schizophrenia trials
      from high-income countries in the same years. Topics covered by the trials will
      be compared with the estimated burden of disease. CONCLUSION: Trials and
      systematic reviews of trials are the gold standard of evaluation of care and
      increasingly provide the basis for recommendations to clinicians, to providers of
      care and to policy makers. Results from this study will present the first
      assessment of the scope, quality and accessibility of mental health trials in low
      and middle-income countries.

PMID- 17002797
TI  - Distress, anxiety, and depression in cancer patients undergoing chemotherapy.
AB  - BACKGROUND: Chemotherapy for cancer is an intense and cyclic treatment associated
      with number of side-effects. The present study evaluated the effect of
      chemotherapy on distress, anxiety and depression. PATIENTS AND METHODS: A total
      of 117 patients were evaluated by using distress inventory for cancer (DIC2) and
      hospital anxiety and depression scale (HADS). Majority of the patients were
      taking chemotherapy for solid tumors (52; 44.4%). RESULTS: The mean distress
      score was 24, 18 (15.38%) were found to have anxiety while 19 (16.23%) had
      depression. High social status was the only factor found to influence distress
      while female gender was the only factor found to influence depression in the
      present study. CONCLUSION: The study highlights high psychological morbidity of
      cancer patients and influence of gender on depression. Construct of distress as
      evaluated by DIC 2 may have a possible overlap with anxiety.

PMID- 17002798
TI  - Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic
      options beyond statins.
AB  - Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment
      and prevention of coronary artery disease. However, despite increasing use of
      statins, a significant number of coronary events still occur and many of such
      events take place in patients presenting with type 2 diabetes and metabolic
      syndrome. More and more attention is being paid now to combined atherogenic
      dyslipidemia which typically presents in patients with type 2 diabetes and
      metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"):
      hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a
      preponderance of small, dense low-density lipoprotein particles and an
      accumulation of cholesterol-rich remnant particles (e.g. high levels of
      apolipoprotein B)--emerged as the greatest "competitor" of low-density
      lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most
      recent extensions of the fibrates trials (BIP - Bezafibrate Infarction Prevention
      study, HHS - Helsinki Heart Study, VAHIT--Veterans Affairs High-density
      lipoprotein cholesterol Intervention Trial and FIELD--Fenofibrate Intervention
      and Event Lowering in Diabetes) give further support to the hypothesis that
      patients with insulin-resistant syndromes such as diabetes and/or metabolic
      syndrome might be the ones to derive the most benefit from therapy with fibrates.
      However, different fibrates may have a somewhat different spectrum of effects.
      Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid
      sequestrants and cholesteryl ester transfer protein inhibition. In addition,
      bezafibrate as pan-peroxisome proliferator activated receptor activator has
      clearly demonstrated beneficial pleiotropic effects related to glucose metabolism
      and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each
      regulate serum lipids by different mechanisms, combination therapy--selected on
      the basis of their safety and effectiveness - may offer particularly desirable
      benefits in patients with combined hyperlipidemia as compared with statins
      monotherapy.

PMID- 17002799
TI  - Homocysteine, vitamin B12 and folate levels in premature coronary artery disease.
AB  - BACKGROUND: Hyperhomocysteinemia is known as an independent risk factor of
      atherosclerosis, but the probable role of hyperhomocysteinemia in premature
      Coronary Artery Disease (CAD) is not well studied. The aim of this study was to
      assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the
      development of premature CAD. METHODS: We performed an analytical case-control
      study on 294 individuals under 45 years (225 males and 69 females) who were
      admitted for selective coronary angiography to two centers in Tehran. RESULTS:
      After considering the exclusion criteria, a total number of 225 individuals were
      enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3
      years (40.1 +/- 4.2 years in males and 39.4 +/- 4.8 years in females). Compared
      to the control group, the level of homocysteine measured in the plasma of the
      male participants was significantly high (14.9 +/- 1.2 versus 20.3 +/- 1.9
      micromol/lit, P = 0.01). However there was no significant difference in
      homocysteine level of females with and without CAD (11.8 +/- 1.3 versus 11.5 +/-
      1.1 micromol/lit, P = 0.87). Mean plasma level of folic acid and vitamin B12 in
      the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these
      findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin
      B12 deficiency. Logistic regression analysis for evaluating independent CAD risk
      factors showed hyperhomocysteinemia as an independent risk factor for premature
      CAD in males (OR = 2.54 0.95% CI 1.23 to 5.22, P = 0.01). Study for the
      underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12
      deficiency had significant influence on incidence of hyperhomocysteinemia.
      CONCLUSION: We may conclude that hyperhomocysteinemia is an independent risk
      factor for CAD in young patients (below 45 years old)--especially in men--and
      vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.

PMID- 17002800
TI  - Substance use and sexual behaviours of Japanese men who have sex with men: a
      nationwide internet survey conducted in Japan.
AB  - BACKGROUND: Japanese men who have sex with men (MSM), especially those living in
      large metropolitan areas such as Tokyo and Osaka, are facing a growing HIV/AIDS
      epidemic. Although the Internet is used as a new venue for meeting sex partners,
      it can also serve as a useful research tool for investigating the risk behaviours
      of Japanese MSM. This Internet survey explored the extent of substance use and
      its association with sexual risk behaviours among Japanese MSM. METHODS: Between
      28 February 2003 and 16 May 2003 MSM were recruited through 57 Japanese gay
      oriented Web sites, gay magazines, and Internet mailing lists. Participants
      completed a structured questionnaire anonymously through the Internet. RESULTS:
      In total, 2,062 Japanese MSM completed the questionnaire. The average age of
      participants was 29.0 years and 70.5% identified as gay, 20.8% as bisexual, and
      8.7% as other. Overall, 34.5% reported never using a substance, 45% reported ever
      using one type of substance (lifetime reported single substance users), and 19.6%
      had used more than 1 type of substance (lifetime reported multiple substance
      users) in their lifetimes. The substances most commonly used were amyl nitrite
      (63.2%), 5-methoxy-N, N-diisopropyltryptamine (5MEO-DIPT) (9.3%), and marijuana
      (5.7%). In the multivariate analysis, unprotected anal intercourse, having had 6
      or more sexual partners, visiting a sex club/gay venue in the previous 6 months,
      a lower education level, and being 30 to 39 years of age were associated with
      both lifetime single and lifetime multiple substance use. Lifetime reported
      multiple substance use was also correlated with having a casual sex partner,
      having symptoms of depression, being diagnosed as HIV-positive, and greater
      HIV/AIDS-related knowledge. CONCLUSION: This is the first Internet-based research
      focused on the sexual and substance use behaviours of MSM in Asia. Our findings
      suggest a compelling need for prevention interventions to reduce HIV risk-related
      substance use behaviours among Japanese MSM. The results also suggest that the
      Internet is potentially a useful tool for collecting behavioural data and
      promoting prevention interventions among this population.

PMID- 17002801
TI  - Modulation of Abeta42 low-n oligomerization using a novel yeast reporter system.
AB  - BACKGROUND: While traditional models of Alzheimer's disease focused on large
      fibrillar deposits of the Abeta42 amyloid peptide in the brain, recent work
      suggests that the major pathogenic effects may be attributed to SDS-stable
      oligomers of Abeta42. These Abeta42 oligomers represent a rational target for
      therapeutic intervention, yet factors governing their assembly are poorly
      understood. RESULTS: We describe a new yeast model system focused on the initial
      stages of Abeta42 oligomerization. We show that the activity of a fusion of
      Abeta42 to a reporter protein is compromised in yeast by the formation of SDS
      stable low-n oligomers. These oligomers are reminiscent of the low-n oligomers
      formed by the Abeta42 peptide in vitro, in mammalian cell culture, and in the
      human brain. Point mutations previously shown to inhibit Abeta42 aggregation in
      vitro, were made in the Abeta42 portion of the fusion protein. These mutations
      both inhibited oligomerization and restored activity to the fusion protein. Using
      this model system, we found that oligomerization of the fusion protein is
      stimulated by millimolar concentrations of the yeast prion curing agent
      guanidine. Surprisingly, deletion of the chaperone Hsp104 (a known target for
      guanidine) inhibited oligomerization of the fusion protein. Furthermore, we
      demonstrate that Hsp104 interacts with the Abeta42-fusion protein and appears to
      protect it from disaggregation and degradation. CONCLUSION: Previous models of
      Alzheimer's disease focused on unravelling compounds that inhibit fibrillization
      of Abeta42, i.e. the last step of Abeta42 assembly. However, inhibition of
      fibrillization may lead to the accumulation of toxic oligomers of Abeta42. The
      model described here can be used to search for and test proteinacious or chemical
      compounds for their ability to interfere with the initial steps of Abeta42
      oligomerization. Our findings suggest that yeast contain guanidine-sensitive
      factor(s) that reduce the amount of low-n oligomers of Abeta42. As many yeast
      proteins have human homologs, identification of these factors may help to uncover
      homologous proteins that affect Abeta42 oligomerization in mammals.

PMID- 17002802
TI  - Non-compacted cardiomyopathy: clinical-echocardiographic study.
AB  - The aim of the present study was to describe the clinical and echocardiographic
      findings of ventricular noncompaction in adult patients. Fifty-three patients
      underwent complete clinical history, electrocardiogram, Holter and transthoracic
      echocardiogram. Forty patients (75%) were in class I/II of the New York Heart
      Association, and 13 (25%) in class III/IV. Ventricular and supraventricular
      escape beats were found in 40% and 26.4%, respectively. Holter showed premature
      ventricular contractions in 32% and sustained ventricular tachycardia in 7.5%.
      Ventricular noncompaction was an isolated finding in 74% of cases and was
      associated with other congenital heart disease in 26%. Noncompacted ventricular
      myocardium involved only left ventricle in 62% of the patients and both
      ventricles in 38%. The mean ratio of noncompacted to compacted myocardial layers
      at the site of maximal wall thickness was 3.4 +/- 0.87 mm (range 2.2-7.5). The
      presence of ventricular noncompaction in more than three segments was associated
      with a functional class greater than II and ventricular arrhythmia with
      demonstrable statistical significance by chi2(p < 0.003). CONCLUSION: a)
      Noncompacted cardiomyopathy is a congenital pathological entity that can occur in
      isolated form or associated with other heart disease and often involves both
      ventricles. b) A ratio of noncompacted to compacted myocardium greater than 3 and
      involvement of three or more segments are indicators of poor prognosis. c) Since
      the clinical manifestations are not sufficient to establish diagnosis,
      echocardiography is the diagnostic tool that makes it possible to document
      ventricular noncompaction and establish prognostic factors.

PMID- 17002803
TI  - Pain-related synaptic plasticity in spinal dorsal horn neurons: role of CGRP.
AB  - BACKGROUND: The synaptic and cellular mechanisms of pain-related central
      sensitization in the spinal cord are not fully understood yet. Calcitonin gene
      related peptide (CGRP) has been identified as an important molecule in spinal
      nociceptive processing and ensuing behavioral responses, but its contribution to
      synaptic plasticity, cellular mechanisms and site of action in the spinal cord
      remain to be determined. Here we address the role of CGRP in synaptic plasticity
      in the spinal dorsal horn in a model of arthritic pain. RESULTS: Whole-cell
      current- and voltage-clamp recordings were made from substantia gelatinosa (SG)
      neurons in spinal cord slices from control rats and arthritic rats (> 6 h
      postinjection of kaolin/carrageenan into the knee). Monosynaptic excitatory
      postsynaptic currents (EPSCs) were evoked by electrical stimulation of afferents
      in the dorsal root near the dorsal root entry zone. Neurons in slices from
      arthritic rats showed increased synaptic transmission and excitability compared
      to controls. A selective CGRP1 receptor antagonist (CGRP8-37) reversed synaptic
      plasticity in neurons from arthritic rats but had no significant effect on normal
      transmission. CGRP facilitated synaptic transmission in the arthritis pain model
      more strongly than under normal conditions where both facilitatory and inhibitory
      effects were observed. CGRP also increased neuronal excitability. Miniature EPSC
      analysis suggested a post- rather than pre-synaptic mechanism of CGRP action.
      CONCLUSION: This study is the first to show synaptic plasticity in the spinal
      dorsal horn in a model of arthritic pain that involves a postsynaptic action of
      CGRP on SG neurons.

PMID- 17002804
TI  - Individual freedom versus collective responsibility: an economic epidemiology
      perspective.
AB  - Individuals' free choices in vaccination do not guarantee social optimum since
      individuals' decision is based on imperfect information, and vaccination decision
      involves positive externality. Public policy of compulsory vaccination or
      subsidised vaccination aims to increase aggregate private demand closer to social
      optimum. However, there is controversy over the effectiveness of public
      intervention compared to the free choice outcome in vaccination, and this article
      provides a brief discussion on this issue. It can be summarised that individuals'
      incentives to vaccination and accordingly their behavioural responses can greatly
      influence public policy's pursuit to control disease transmission, and compulsory
      (or subsidised) vaccination policy without incorporating such behavioural
      responses will not be able to achieve the best social outcome.

PMID- 17002805
TI  - A machine learning strategy to identify candidate binding sites in human protein
      coding sequence.
AB  - BACKGROUND: The splicing of RNA transcripts is thought to be partly promoted and
      regulated by sequences embedded within exons. Known sequences include binding
      sites for SR proteins, which are thought to mediate interactions between splicing
      factors bound to the 5' and 3' splice sites. It would be useful to identify
      further candidate sequences, however identifying them computationally is hard
      since exon sequences are also constrained by their functional role in coding for
      proteins. RESULTS: This strategy identified a collection of motifs including
      several previously reported splice enhancer elements. Although only trained on
      coding exons, the model discriminates both coding and non-coding exons from
      intragenic sequence. CONCLUSION: We have trained a computational model able to
      detect signals in coding exons which seem to be orthogonal to the sequences'
      primary function of coding for proteins. We believe that many of the motifs
      detected here represent binding sites for both previously unrecognized proteins
      which influence RNA splicing as well as other regulatory elements.

PMID- 17002806
TI  - Inhalation of the Rho-kinase inhibitor Y-27632 reverses allergen-induced airway
      hyperresponsiveness after the early and late asthmatic reaction.
AB  - BACKGROUND: In guinea pigs, we have previously demonstrated that the contribution
      of Rho-kinase to airway responsiveness in vivo and ex vivo is enhanced after
      active sensitization with ovalbumin (OA). Using conscious, unrestrained OA
      sensitized guina pigs, we now investigated the role of Rho-kinase in the
      development of airway hyperresponsiveness (AHR) after the allergen-induced early
      (EAR) and late asthmatic reaction (LAR) in vivo. METHODS: Histamine and PGF2alpha
      PC100-values (provocation concentrations causing 100% increase in pleural
      pressure) were assessed before OA-challenge (basal airway responsiveness) and
      after the OA-induced EAR (5 h after challenge) and LAR (23 h after challenge).
      Thirty minutes later, saline or the specific Rho-kinase inhibitor Y-27632 (5 mM,
      nebulizer concentration) were nebulized, after which PC100-values were
      reassessed. RESULTS: In contrast to saline, Y-27632 inhalation significantly
      decreased the basal responsiveness toward histamine and PGF2alpha before OA
      challenge, as indicated by increased PC100 -values. Both after the allergen
      induced EAR and LAR, AHR to histamine and PGF2alpha was present, which was
      reversed by Y-27632 inhalation. Moreover, there was an increased effectiveness of
      Y-27632 to reduce airway responsiveness to histamine and PGF2alpha after the EAR
      and LAR as compared to pre-challenge conditions. Saline inhalations did not
      affect histamine or PGF2alpha PC100-values at all. Interestingly, under all
      conditions Y-27632 was significantly more effective in reducing airway
      responsiveness to PGF2alpha as compared to histamine. Also, there was a clear
      tendency (P = 0.08) to a more pronounced degree of AHR after the EAR for
      PGF2alpha than for histamine. CONCLUSION: The results indicate that inhalation of
      the Rho-kinase inhibitor Y-27632 causes a considerable bronchoprotection to both
      histamine and PGF2alpha. Moreover, the results are indicative of a differential
      involvement of Rho-kinase in the agonist-induced airway obstruction in vivo.
      Increased Rho-kinase activity contributes to the allergen-induced AHR to
      histamine and PGF2alpha after both the EAR and the LAR, which is effectively
      reversed by inhalation of Y-27632. Therefore, Rho-kinase can be considered as a
      potential pharmacotherapeutical target in allergic asthma.

PMID- 17002807
TI  - HIV-1 designed to use different tRNAGln isoacceptors prefers to select tRNAThr
      for replication.
AB  - BACKGROUND: Previous studies have shown that infection with human
      immunodeficiency virus type 1 (HIV-1) causes acceleration of the synthesis of
      glutamine tRNA (tRNAGln) in infected cells. To investigate whether this might
      influence HIV-1 to utilize tRNAGln as a primer for initiation of reverse
      transcription, we have constructed HIV-1 proviral genomes in which the PBS and
      the A-loop region upstream of the PBS have been made complementary to either the
      anticodon region of tRNAGln,1 or tRNAGln,3 and 3' terminal 18 nucleotides of each
      isoacceptor of tRNAGln. RESULTS: Viruses in which the PBS was altered to be
      complementary to tRNAGln,1 or tRNAGln,3 with or without the A-loop all exhibited
      a lower infectivity than the wild type virus. Viruses with only the PBS
      complementary to tRNAGln,1 or tRNAGln,3 reverted to wild type following culture
      in SupT1 cells. Surprisingly, viruses in which the PBS and A-loop were
      complementary to tRNAGln,1 did not grow in SupT1 cells, while viruses in which
      the PBS and A-loop were made complementary to tRNAGln,3 grew slowly in SupT1
      cells. Analysis of the PBS of this virus revealed that it had reverted to select
      tRNAThr as the primer, which shares complementarity in 15 of 18 nucleotides with
      the PBS complementary to tRNAGln,3. CONCLUSION: The results of these studies
      support the concept that the HIV-1 has preferred tRNAs that can be selected as
      primers for replication.

PMID- 17002808
TI  - A brief symptom index for advanced renal cell carcinoma.
AB  - BACKGROUND: Our objective was to test a brief, symptom index for advanced renal
      cell carcinoma, a disease affecting over 38,000 Americans each year and often
      diagnosed in late stages. METHODS: We conducted secondary data analyses on
      patient-reported outcomes of 209 metastatic renal cell carcinoma patients
      participating in a Phase III clinical trial. Patient-reported outcomes, obtained
      from the FACT-Biological Response Modifier (FACT-BRM) scale, were available at
      baseline, 2, and 8 weeks. We analyzed data from eight FACT-BRM items previously
      identified by clinical experts to represent the most important symptoms of
      advanced renal cell carcinoma. Items comprising this index assess nausea, pain,
      appetite, perceived sickness, fatigue and weakness, with higher scores indicating
      fewer symptoms. We determined reliability and validity of the index and estimated
      a minimally important difference. RESULTS: The index had excellent internal
      reliability at all three time points (alphas > or = 0.83). Baseline scores were
      able to discriminate patients across Karnofsky performance status, number of
      metastatic sites, and risk group categories (ps < .01). Mean index scores
      declined over time likely indicative of the toxic nature of the administered
      treatments. Distribution- and anchor-based methods converged on a minimally
      important difference estimate of 2 to 3 points. CONCLUSION: The 8-item index of
      patient-reported symptoms of renal cell carcinoma appears to be a
      psychometrically sound measure. It is a brief, reliable, and valid measure that
      can easily be adapted for use in clinical trials and observational studies.

PMID- 17002809
TI  - Mastery, perceived stress and health-related behaviour in northeast Arnhem Land:
      a cross-sectional study.
AB  - BACKGROUND: Indigenous peoples in Australia are disadvantaged on all markers of
      health and social status across the life course. Psychosocial factors are
      implicated in the aetiology of chronic diseases and in pathways underpinning
      social health disparities. Minimal research has investigated psychosocial factors
      and health in Indigenous peoples. This study evaluated associations between
      mastery, perceived stress, and health-related behaviour for a remote Indigenous
      population in Australia. METHODS: Complete data on mastery (the degree to which
      individuals feel in control of their lives), perceived stress, physical activity,
      and fruit and vegetable consumption were obtained for 177 participants in a
      community-based chronic disease risk factor survey. Psychosocial questionnaires
      were completed as an option during community screening (response rate = 61.9%).
      Extensive consultation facilitated the cross-cultural adaptation of measures.
      RESULTS: Mastery was inversely correlated with perceived stress measures (p <
      0.009): recent stress, r = -0.47; chronic stress, r = -0.41; and youth stress, r
      = -0.30. Relationships between mastery and behaviour varied according to age
      group (<25 or > or =25 years) for physical activity (p = 0.001) and vegetable
      consumption (p = 0.005). Individuals aged > or =25 years engaging in < or =2
      bouts of physical activity/week had lower mastery than individuals engaging in >
      or =3 bouts/week, with means (95% CI) of 14.8 (13.7-15.8) and 17.1 (15.3-19.0),
      respectively (p = 0.026). Individuals aged > or =25 years eating vegetables < or
      =3 times/week had lower mastery than those eating vegetables > or =4 times/week
      (p = 0.009) [means 14.7 (13.8-15.5) and 17.3 (15.5-19.1), respectively].
      Individuals <25 years engaging in < or =2 bouts of physical activity/week had
      greater mastery than individuals engaging in > or =3 bouts/week (p = 0.022)
      [means 17.2 (15.2-19.2) and 13.8 (11.9-15.7), respectively]. For men > or =25
      years and women > or =15 years, mastery was inversely related to age (p < 0.002).
      Men <25 years had less mastery than women of equivalent age (p = 0.001) [means
      13.4 (12.1-14.7) and 17.5 (15.3-19.8), respectively]. CONCLUSION: Consistent with
      previous research, this study provides additional support for a link between
      mastery and health-related behaviour, and extends evidence of this association to
      a remote Indigenous population. Mastery's association with perceived stress, its
      age-specific association with health behaviour, and findings of low mastery
      amongst young men, highlights a need for life course research accounting for
      contextual factors affecting Indigenous peoples.

PMID- 17002811
TI  - Hemangioma in minor salivary glands: real or illusion.
AB  - Hemangioma is a common soft tissue lesion in the head and neck region. Hemangioma
      in the context of minor salivary glands is rarely encountered in surgical
      pathology practice, and for this reason most pathologist are often unfamiliar
      with its histomorphological features. We report a rare histological finding of
      salivary gland structures within a cavernous hemangioma, which may or may not
      have originated in the minor salivary gland.

PMID- 17002810
TI  - Methodology for the Randomised Injecting Opioid Treatment Trial (RIOTT):
      evaluating injectable methadone and injectable heroin treatment versus optimised
      oral methadone treatment in the UK.
AB  - Whilst unsupervised injectable methadone and diamorphine treatment has been part
      of the British treatment system for decades, the numbers receiving injectable
      opioid treatment (IOT) has been steadily diminishing in recent years. In
      contrast, there has been a recent expansion of supervised injectable diamorphine
      programs under trial conditions in a number of European and North American
      cities, although the evidence regarding the safety, efficacy and cost
      effectiveness of this treatment approach remains equivocal. Recent British
      clinical guidance indicates that IOT should be a second-line treatment for those
      patients in high-quality oral methadone treatment who continue to regularly
      inject heroin, and that treatment be initiated in newly-developed supervised
      injecting clinics. The Randomised Injectable Opioid Treatment Trial (RIOTT) is a
      multisite, prospective open-label randomised controlled trial (RCT) examining the
      role of treatment with injected opioids (methadone and heroin) for the management
      of heroin dependence in patients not responding to conventional substitution
      treatment. Specifically, the study examines whether efforts should be made to
      optimise methadone treatment for such patients (e.g. regular attendance,
      supervised dosing, high oral doses, access to psychosocial services), or whether
      such patients should be treated with injected methadone or heroin. Eligible
      patients (in oral substitution treatment and injecting illicit heroin on a
      regular basis) are randomised to one of three conditions: (1) optimized oral
      methadone treatment (Control group); (2) injected methadone treatment; or (3)
      injected heroin treatment (with access to oral methadone doses). Subjects are
      followed up for 6-months, with between-group comparisons on an intention-to-treat
      basis across a range of outcome measures. The primary outcome is the proportion
      of patients who discontinue regular illicit heroin use (operationalised as
      providing >50% urine drug screens negative for markers of illicit heroin in
      months 4 to 6). Secondary outcomes include measures of other drug use, injecting
      practices, health and psychosocial functioning, criminal activity, patient
      satisfaction and incremental cost effectiveness. The study aims to recruit 150
      subjects, with 50 patients per group, and is to be conducted in supervised
      injecting clinics across England.

PMID- 17002812
TI  - Oxygen uptake kinetics following 20 days of unilateral lower limb suspension.
AB  - The purpose of the present study was to examine the effect of unilateral lower
      limb suspension (ULLS) deconditioning on oxygen uptake kinetics. Eight healthy
      males underwent ULLS for 20 days and performed a series of 6-min square-wave
      transitions from rest to 60-W single-leg cycling exercises just before and after
      ULLS. To characterize the kinetics of the oxygen uptake response, a single
      exponential model was applied to the data until the end of the fast component
      omitted the first 15 s of the on-transit using a nonlinear least-squares fitting
      procedure. The following results were found: (i) the time constant of oxygen
      uptake was unchanged before and after ULLS; (ii) although there was no
      significant difference in the baseline and the asymptotic amplitude of the fast
      component, the asymptote, i.e., the absolute asymptotic amplitude of the fast
      component (the sum of the baseline and the asymptotic amplitude), and the end
      exercise oxygen uptake were decreased after ULLS; (iii) the contribution of the
      slow component to the total response of oxygen uptake was unchanged at pre- and
      post-ULLS. In conclusion, the asymptote in the fast component and the end
      exercise oxygen uptake were decreased after 20-d ULLS, though the response speed
      and the amplitude of the slow component of oxygen uptake were not changed. It is
      suggested that deconditioning as a result of limb disuse affects oxygen uptake
      response.

PMID- 17002813
TI  - Gastric arrhythmia and nausea of motion sickness induced in healthy Japanese
      subjects viewing an optokinetic rotating drum.
AB  - The purpose of this study was to investigate whether nausea or gastric
      dysrhythmia, including tachygastria, which was determined by electrogastrography
      (EGG), were observed during optokinetic motion sickness in healthy Japanese
      volunteers. Twelve volunteers (9 men and 3 women) participated in the study. The
      subjects were asked to sit in a chair with their heads positioned in the center
      of a drum whose inside had been painted with black and white stripes. After a 15
      min resting period, the drum was rotated at a speed of 60 degree/sec for 15 min.
      The EGG was continuously recorded for a total of 45 min (15 min resting period,
      15 min rotation period, and 15 min recovery period). The severity of nausea was
      evaluated with a visual analogue scale (VAS) before, immediately after, and 15
      min after the cessation of drum rotation. Other motion sickness symptoms were
      evaluated by scores of subjective symptoms of motion sickness (SSMS). Of 12
      subjects who completed the study, 10 complained of nausea immediately after
      cessation of drum rotation. The VAS score for nausea immediately after the drum
      rotation period and 15 min after cessation of the rotation was significantly
      higher than during the resting period. The EGG during the drum rotation period
      showed a decrease in normogastria, which was accompanied with an increase in
      tachygastria. We conclude that gastric tachyarrhythmia and nausea may be induced
      by viewing an optokinetic rotating drum in healthy Japanese subjects who may have
      a hypersusceptibility to vection-induced motion sickness. The gastric dysrhythmia
      obtained with EGG could be a useful observation to support the appearance of
      nausea induced by optokinetic motion sickness.

PMID- 17002817
TI  - O(2)-responsive chemical sensors based on hybrid xerogels that contain
      fluorinated precursors.
AB  - We report the development and analytical figures of merit associated with several
      new O(2)-responsive sensor materials. These new sensing materials are formed by
      sequestering the luminophore tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)
      ([Ru(dpp)(3)](2+)) within hybrid xerogels that are composed of two of the
      following methoxysilanes: tetramethoxysilane, n-propyl-trimethoxysilane, 3,3,3
      trifluoropropyl-trimethoxysilane, phenethyl-trimethoxysilane, and
      pentafluorophenylpropyl-trimethoxysilane. Steady-state and time-resolved
      luminescence measurements are used to investigate these hybrid xerogel-based
      sensor materials and elucidate the underlying reasons for the observed
      performance. The results show that many of the [Ru(dpp)(3)](2+)-doped composites
      form visually uniform, crack-free xerogel films that can be used to construct
      O(2) sensors that have linear calibration curves and excellent long-term
      stability. To the best of our knowledge, the [Ru(dpp)(3)](2+)-doped fluorinated
      hybrid xerogels also exhibit the highest O(2) sensitivity of any reported
      [Ru(dpp)(3)](2+)-based sensor platform.

PMID- 17002818
TI  - Fluorescence of aromatic amines and their fluorescamine derivatives for detection
      of explosive vapors.
AB  - Nitroaromatics (such as dinitrotoluene, trinitrotoluene, and nitrobenzene) found
      in explosive vapors from buried landmines can be reduced to aminoaromatics by a
      novel process involving Pd metal nanocatalysts prepared in supercritical fluid
      carbon dioxide and supported on multi-walled carbon nanotubes. These
      aminoaromatics are fluorescent and, if desired, the fluorescence yield can be
      increased and the fluorescence maxima shifted further toward the red by reaction
      with appropriate derivatizing agents such as fluorescamine. Corrected spectra for
      these chemicals and their derivatives are included. Subpicomolar detection limits
      have already been achieved using a laboratory spectrofluorometer with a 150 W Xe
      arc lamp. Using lasers as excitation sources, this approach has the potential for
      developing a field sensor competitive with other methods currently used for
      detecting explosive vapors from land mines.

PMID- 17002819
TI  - Fluorescence-suppressed Raman technique for quantitative analysis of protein
      solution using a micro-Raman probe, the shifted excitation method, and partial
      least squares regression analysis.
AB  - A practical Raman analyzing technique with suppression of the strong fluorescent
      background in order to obtain quantitative information is proposed in the present
      study. The technique is based on the shifted excitation method and partial least
      squares regression (PLSR) analysis. The Raman system consists of a single Raman
      spectrometer, a background-free electrically tunable Ti:Sapphire laser (BF-ETL),
      and a micro-Raman probe (MRP). The system allows one to obtain reliable shifted
      excitation Raman spectra with a simple operation. The PLSR analysis successfully
      provides quantitative information from the obtained spectra with the suppression
      of random noise including photon shot noise. The present study demonstrates that
      the technique is effective for extracting quantitative information concealed
      behind a fluorescent background that is more than 200 times stronger than the
      Raman signal.

PMID- 17002820
TI  - Studying bacterial metabolic states using Raman spectroscopy.
AB  - Natural metabolic variability expected during characteristic growth phases in
      batch cultures of Escherichia coli and Staphylococcus epidermidis were studied by
      Raman spectroscopy. Spectral changes induced by metabolic changes found in the
      growth phases (i.e., lag, exponential, stationary, and decay) were identified.
      Maximum intensity of bands assigned to DNA and RNA bases are seen at the
      beginning of the exponential phase, when cells are metabolically active, and
      minimum intensities are seen when cells are decaying. High agreement in spectral
      variation due to growth phases was seen for all the trials that were performed,
      four growth cycles for E. coli and two for S. epidermidis. Batch cultures were
      monitored by standard plate counts to identify all growth phases, including
      decay. Spectral data were analyzed by principal component analysis (PCA) and
      discriminant analysis to identify similarities and differences and to estimate a
      classification performance based on growth phases. For the species evaluated,
      spectra during decay are grouped closer to each other and separated from lag,
      exponential, and stationary cells. These results suggest that Raman spectroscopy
      can be used to study metabolic states in bacteria and in particular cell
      viability.

PMID- 17002821
TI  - Analysis of the effect of particle size on polymorphic quantitation by Raman
      spectroscopy.
AB  - Raman spectroscopy has been widely used to monitor various aspects of the
      crystallization process. Although it has long been known that particle size can
      influence Raman signal, relatively little research has been conducted in this
      area, in particular for mixtures of organic materials. The aim of this study was
      to investigate the effect of particle size on quantification of polymorphic
      mixtures. Several sets of calibration samples containing different particle size
      fractions were prepared and Raman spectra were collected with different probes.
      Calibration models were built using both univariate and multivariate analysis. It
      was found that, for a single component system, Raman intensity decreased with
      increasing particle size. For mixtures, calibration models generated from the
      same particle size distribution as the sample yielded relatively good predictions
      of the actual sample composition. However, if the particle sizes of the
      calibration and unknown samples were different, prediction errors resulted. For
      extreme differences in particle sizes, prediction errors of up to 20% were
      observed. Prediction errors could be minimized by changing the sampling optics
      employed.

PMID- 17002822
TI  - In situ Raman spectroscopic study of the dissociation of methane hydrate at high
      pressure.
AB  - The dissociation of methane hydrate at high pressure is studied by in situ Raman
      spectroscopy in a diamond-anvil cell. As for the Raman spectrum of sI methane
      hydrate, the v(1) band of CH(4) is split into two peaks v'(1) and v''(1),
      indicating the partitioning of CH(4) between the large (5(12)6(2)) and small
      (5(12)) cavities, respectively. With increasing temperature, the intensity ratio
      of Iv'(1)/Iv''(1) decreases obviously, and the d(Iv'(1)/Iv''(1))/dT is -0.079 K(
      1). Additionally, the v(1) band of the dissolved CH(4) is close to v''(1) of the
      CH(4) molecule engaged in the small 5(12) cavity. This implies that, in the
      initial stage of hydrate formation, the abundance of small 5(12) cavities is
      greater than that of large 5(12)6(2) cavities.

PMID- 17002823
TI  - Hole-enhanced Raman scattering.
AB  - Stokes and anti-Stokes non-resonant hole-enhanced Raman scattering (HERS) spectra
      with high signal-to-noise ratio (S/N) are reported for the first time for aqueous
      phase R6G molecules adsorbed onto random nanoholes in thin gold films. Compared
      to conventional surface-enhanced Raman scattering from nanometric gold colloid
      particles, HERS exhibits higher strength gain, exceptional reproducibility,
      simple and reliable substrate preparation, and excellent mechanical stability. By
      correlating the hole density with Raman scattering gain, we determined optimum
      HERS gain for 50 nm diameter holes at approximately 100 holes/microm(2).
      Providing a Raman substrate with uniform "hot spots", we expect that HERS will
      make the quantitative Raman analysis of biological molecules possible.

PMID- 17002825
TI  - Using the Kramers-Kronig method to determine optical constants and evaluating its
      suitability as a linear transform for near-normal front-surface reflectance
      spectra.
AB  - In this paper, the suitability of using the Kramers-Kronig transform to routinely
      extract optical constants from near-normal incidence reflectance spectra of
      solids and liquids is demonstrated. In addition, the possibility of utilizing the
      Kramers-Kronig transform as a linearizing transform for near-normal incidence
      reflectance spectra is investigated. Also, several commercial Kramers-Kronig
      software packages were utilized in determining the optical constants from the
      near-normal incidence reflectance of Plexiglas. Unexpectedly, the results
      produced by the various packages differed significantly. The near-normal
      reflectance of water was measured, the Kramers-Kronig transform was applied to
      extract the optical constants of water, and the result was compared to values
      found in the literature. Furthermore, the Kramers-Kronig transforms of near
      normal incidence reflectance spectra of various concentrations of sugar in water
      were calculated to evaluate its use as a linearizing transform for quantitative
      applications.

PMID- 17002824
TI  - Surface plasmon resonance investigations of human epidermal growth factor
      receptor 2.
AB  - This investigation utilizes surface plasmon resonance (SPR) spectroscopy to
      detect and quantify human epidermal growth factor receptor 2 (HER-2), an oncogene
      product that is over-expressed in some aggressive forms of breast cancer.
      Specifically, the HER-2 trans-membrane protein p185 and its extra cellular
      fragment p105 are analytes targeted in this work by using a gold-based biosensor
      slide on which an anti-HER-2 antibody has been immobilized by attachment to
      Protein G that is fixed to the gold film. A detection limit of > or =11 ng/mL for
      p185 resulted when trastuzumab was used as the anti-HER-2 antibody on the
      biosensor slide. Experiments with semi-purified p105 revealed that it binds
      weakly and reversibly to trastuzumab, therefore complicating its detection and
      quantification. Results of studies that reacted a 13-amino-acid peptide (PP13)
      from the HER-2 kinase domain with its specific antibody were critically different
      than p185 and p105 studies. Spectral analysis of the reflectivity at constant
      bulk buffer refractive index revealed a progressive negative SPR shift over time.
      A negative shift suggests that a loss of protein mass from the anti-PP13 antibody
      Protein G biosensor is occurring. Several possibilities that may explain these
      negative SPR shifts are discussed.

PMID- 17002826
TI  - Nitrate determination using anion exchange membrane and mid-infrared
      spectroscopy.
AB  - This study investigates the combined use of an anion exchange membrane and
      transmittance mid-infrared spectroscopy for determining nitrate concentration in
      aqueous solutions and soil pastes. The method is based on immersing a small piece
      (2 cm(2)) of anion exchange membrane into 5 mL of solution or soil paste for 30
      minutes, after which the membrane is removed, rinsed, and wiped dry. The
      absorbance spectrum of the charged membrane is then used to determine the amount
      of nitrate sorbed on the membrane. At the levels tested, the presence of
      carbonate or phosphate does not affect the nitrate sorption or the spectrum of
      the charged membrane in the vicinity of the nitrate band. Sulfate affects the
      spectrum of the charged membrane but does not prevent nitrate determination. For
      soil pastes, nitrate sorption is remarkably independent of the soil composition
      and is not affected by the level of soil constituents such as organic matter,
      clay, and calcium carbonate. Partial least squares analysis of the membrane
      spectra shows that there exists a strong correlation between the nitrate charge
      and the absorbance in the 1000-1070 cm(-1) interval, which includes the v(1)
      nitrate band located around 1040 cm(-1). The prediction errors range from 0.8 to
      2.1 mueq, which, under the specific experimental conditions, corresponds to
      approximately 2 to 6 ppm N-NO(3)(-) on a solution basis or 2 to 5 mg [N]/kg [dry
      soil] on a dry soil basis.

PMID- 17002827
TI  - Combining the tape-lift method and Fourier transform infrared spectroscopic
      imaging for forensic applications.
AB  - Conventional Fourier transform infrared (FT-IR) spectroscopy and microscopy have
      been widely used in forensic science. New opportunities exist to obtain chemical
      images and to enhance the spatial resolution using attenuated total reflection
      (ATR) FT-IR spectroscopy coupled with a focal-plane array (FPA) detector. In this
      paper, the sensitivity limits of FT-IR imaging using three different ATR crystals
      (Ge, ZnSe, and diamond) in three different optical arrangements for the detection
      of model particles is discussed. Model systems of ibuprofen and paracetamol
      particles having sizes below 32 mum were studied. The collection of drug
      particles was achieved with the aid of two different tapes: common adhesive tape
      and a film of polydimethylsiloxane (PDMS). The surface of the film with collected
      particles was measured directly via ATR-FT-IR imaging. Since the removal of tape
      from porous surfaces can be difficult, the application of micro ATR-FT-IR imaging
      directly to the surface of a newspaper contaminated with particles of model drugs
      is also discussed. In order to assess the feasibility of the chosen method in a
      forensic case study, the detection of diacetylmorphine hydrochloride traces in
      PDMS matrix and the finger surface is investigated. The scenarios considered were
      that of the detection of evidence collected at a crime scene with the tape lift
      method and the analysis of the finger of an individual after drug handling. The
      results show broad implications in the detection of drugs of abuse.

PMID- 17002828
TI  - Cell discrimination by attenuated total reflection-Fourier transform infrared
      spectroscopy: the impact of preprocessing of spectra.
AB  - Fourier transform infrared (FT-IR) spectroscopy has become a powerful tool for
      biodiagnostics and cell line classification. Typical experimental perturbations
      included in spectra are baseline shift and scale variation between spectra. They
      have to be removed by data preprocessings to allow further data analysis and
      classification. In this work, we addressed baseline shift corrections and
      normalizations in attenuated total reflection (ATR) FT-IR spectra. We compared
      the efficiency of several preprocessing methods with series of spectra containing
      typical perturbations (baseline shift, scaling factor, and noise) and a priori
      known definite spectral difference. Several baseline-correction and normalization
      possibilities were evaluated. Our results were generally sensitive, selective,
      and robust with respect to baseline and scaling. Full-range scaling generated
      more false-positive results. Use of first- and second-derivative spectra was
      tested. Results obtained on model spectra were confirmed with series of spectra
      from sensitive and multidrug-resistant leukemia K562 cells. We showed that the
      use of derived spectra did not provide more efficiency and required additional
      preprocessing such as smoothing to obtain results similar to those obtained from
      non-derived ones. On the other hand, results obtained with derivatives were less
      sensitive to scaling, a useful feature when scaling is problematic.

PMID- 17002829
TI  - Correcting attenuated total reflection-Fourier transform infrared spectra for
      water vapor and carbon dioxide.
AB  - Fourier transform infrared (FT-IR) spectroscopy is a valuable technique for
      characterization of biological samples, providing a detailed fingerprint of the
      major chemical constituents. However, water vapor and CO(2) in the beam path
      often cause interferences in the spectra, which can hamper the data analysis and
      interpretation of results. In this paper we present a new method for removal of
      the spectral contributions due to atmospheric water and CO(2) from attenuated
      total reflection (ATR)-FT-IR spectra. In the IR spectrum, four separate
      wavenumber regions were defined, each containing an absorption band from either
      water vapor or CO(2). From two calibration data sets, gas model spectra were
      estimated in each of the four spectral regions, and these model spectra were
      applied for correction of gas absorptions in two independent test sets (spectra
      of aqueous solutions and a yeast biofilm (C. albicans) growing on an ATR crystal,
      respectively). The amounts of the atmospheric gases as expressed by the model
      spectra were estimated by regression, using second-derivative transformed
      spectra, and the estimated gas spectra could subsequently be subtracted from the
      sample spectra. For spectra of the growing yeast biofilm, the gas correction
      revealed otherwise hidden variations of relevance for modeling the growth
      dynamics. As the presented method improved the interpretation of the principle
      component analysis (PCA) models, it has proven to be a valuable tool for
      filtering atmospheric variation in ATR-FT-IR spectra.

PMID- 17002830
TI  - Water evaporation analysis of L-phenylalanine from initial aqueous solutions to
      powder state by vibrational spectroscopy.
AB  - The water evaporation from L-phenylalanine (L-phe) aqueous solutions at different
      initial pH (0-13) was studied by vibrational spectroscopy. Next, the attenuated
      total reflection-Fourier transform infrared (ATR-FT-IR) spectra of aqueous
      solutions were compared to those recorded after drying for 72 h at 21 degrees C
      at appropriate initial pH values. Micro-Raman results collected after the water
      evaporation process are also presented and interpreted. Between pH = 2.5 and 8.76
      a white non-transparent gel was observed, possibly due to the presence of the
      NaCl salt. The significant differences of the band intensities of L-phe
      functional groups noticed at pH near pK(a) values indicate the structural changes
      of L-phe molecules due to dimer formation (hydrogen bonds between the -COOH and 
      CO(2)(-) groups, and the -NH(3)(+) and -NH(2) groups). The presence of the
      hydrophobic interactions leads to the aggregation of L-phe molecules, most
      probably via phe-phe stacking as well as complexes of phe with Na(+) ions, HCl,
      or H(2)O molecules.

PMID- 17002831
TI  - A study on water adsorption onto microcrystalline cellulose by near-infrared
      spectroscopy with two-dimensional correlation spectroscopy and principal
      component analysis.
AB  - Water adsorption onto microcrystalline cellulose (MCC) in the moisture content
      (M(c)) range of 0.2-13.4 wt % was investigated by near-infrared (NIR)
      spectroscopy. In order to distinguish heavily overlapping O-H stretching bands in
      the NIR region due to MCC and water, principal component analysis (PCA) and
      generalized two-dimensional correlation spectroscopy (2DCOS) were applied to the
      obtained spectra. The NIR spectra in four adsorption stages separated by PCA were
      analyzed by 2DCOS. For the low M(c) range of 0.2-3.1 wt %, a decrease in the free
      or weakly hydrogen-bonded (H-bonded) MCC OH band, increases in the H-bonded MCC
      OH bands, and increases in the adsorbed water OH bands are observed. These
      results suggest that the inter- and intrachain H-bonds of MCC are formed by
      monomeric water molecule adsorption. In the M(c) range of 3.8-7.1 wt %, spectral
      changes in the NIR spectra reveal that the aggregation of water molecules starts
      at the surface of MCC. For the high M(c) range of 8.1-13.4 wt %, the NIR results
      suggest that the formation of bulk water occurs. It is revealed from the present
      study that approximately 3-7 wt % of adsorbed water is responsible for the
      stabilization of the H-bond network in MCC at the cellulose-water surface.

PMID- 17002832
TI  - Use of artificial neural networks in near-infrared reflectance spectroscopy
      calibrations for predicting the inclusion percentages of wheat and sunflower meal
      in compound feedingstuffs.
AB  - The use of near-infrared reflectance spectroscopy (NIRS) calibrations to predict
      the ingredient composition in compound feeds (i.e., inclusion percentage of each
      ingredient) is a complex task, regarding both the nature of the parameters to be
      predicted, since they are not well-defined chemical entities, and the
      heterogeneousness of the matrices/formulas in which each ingredient participates.
      The present paper evaluates the use of nonlinear regression methods, such as
      artificial neural networks (ANN), for developing NIRS calibrations to predict
      these parameters. Two of the most representative ingredients in the Spanish
      compound feed formulations (wheat and sunflower meal) were selected for
      evaluating ANN possibilities, using a large spectral library comprising a total
      of 7523 commercial compound feed samples; 7423 were used as training set and 100
      as validation set. Three general models of networks were studied: multilayer
      perceptron with back-propagation training (BP), multilayer perceptron with
      Levenberg-Maquartd training (LM), and radial basis function nets (RBF); moreover,
      in accordance with a factorial design, more complex architectures were evaluated
      gradually, changing the number of hidden layers and hidden neurons, for the
      determination of the optimal network topology. For both ingredients, the best
      results were obtained using ANN with BP training, showing prediction error values
      (SEP) of 2.72% and 0.66% for wheat and sunflower meal, respectively. These SEP
      values showed a significant improvement (19%-49% for sunflower meal and wheat,
      respectively) in comparison with those obtained using calibrations developed with
      linear methods.

PMID- 17002833
TI  - Removal of analyte-irrelevant variations in near-infrared tissue spectra.
AB  - This paper describes mathematical techniques to correct for analyte-irrelevant
      optical variability in tissue spectra by combining multiple preprocessing
      techniques to address variability in spectral properties of tissue overlying and
      within the muscle. A mathematical preprocessing method called principal component
      analysis (PCA) loading correction is discussed for removal of inter-subject,
      analyte-irrelevant variations in muscle scattering from continuous-wave diffuse
      reflectance near-infrared (NIR) spectra. The correction is completed by
      orthogonalizing spectra to a set of loading vectors of the principal components
      obtained from principal component analysis of spectra with the same analyte
      value, across different subjects in the calibration set. Once the loading vectors
      are obtained, no knowledge of analyte values is required for future spectral
      correction. The method was tested on tissue-like, three-layer phantoms using
      partial least squares (PLS) regression to predict the absorber concentration in
      the phantom muscle layer from the NIR spectra. Two other mathematical methods,
      short-distance correction to remove spectral interference from skin and fat
      layers and standard normal variate scaling, were also applied and/or combined
      with the proposed method prior to the PLS analysis. Each of the preprocessing
      methods improved model prediction and/or reduced model complexity. The
      combination of the three preprocessing methods provided the most accurate
      prediction results. We also performed a preliminary validation on in vivo human
      tissue spectra.

PMID- 17002834
TI  - Circulating blood volume determination using electronic spin resonance
      spectroscopy.
AB  - There have been numerous methods proposed to measure the circulating blood volume
      (CBV). Nevertheless, none of them have been massively and routinely accepted in
      clinical diagnosis. This study describes a simple and rapid method, on a rabbit
      model, using the dilution of autologous red cells labeled with a nitroxide
      radical (Iodoacetamide-TEMPO), which can be detected by electronic spin resonance
      (ESR) spectroscopy. Blood samples were withdrawn and re-injected using the ears'
      marginal veins. The average CBV measured by the new method/body weight
      (CBV(IAT)/BW) was 59 +/- 7 mL/kg (n = 33). Simultaneously, blood volume
      determinations using the nitroxide radical and (51)Cr (CBV(Cr)) were performed.
      In the plot of the difference between the methods (CBV(IAT) - CBV(Cr)) against
      the average (CBV(IAT) + CBV(Cr))/2, the mean of the bias was -1.1 +/- 6.9 mL and
      the limits of agreement (mean difference +/-2 SD) were -14.9 and 12.7 mL. Lin's
      concordance correlation coefficient p(c) = 0.988. Thus, both methods are in close
      agreement. The development of a new method that allows a correct estimation of
      the CBV without using radioactivity, avoiding blood manipulation, and decreasing
      the possibility of blood contamination with similar accuracy and precision of
      that of the "gold standard method" is an innovative proposal.

PMID- 17002835
TI  - Nonlinear forward scattering in cesium vapor: experiment with simultaneous
      scanning of laser frequency and B-field.
AB  - We present the results of an experimental study of nonlinear magneto-optical
      rotation in a buffer-gas-free uncoated Cs cell on hyperfine transitions F(g) = 3 
      -> F(e) = 2, 3, 4 of the D(2) line at high laser irradiance (up to 40 mW/cm(2)).
      The measurements were done in a forward scattering configuration, with
      simultaneous linear scanning of laser frequency and magnetic field at different
      temporal rates. The latter revealed, in a single measurement, the dependences of
      maximum nonlinear Faraday signal and the corresponding B-field on the laser
      frequency within the Doppler profile.

PMID- 17002836
TI  - Light-emitting-diode-based light source for calibration of an intensified charge
      coupled device detection system intended for galvanoluminescence measurements.
AB  - A spectrally tunable light source utilizing three light-emitting diodes (LEDs)
      for calibration of a highly sensitive intensified charge-coupled device (ICCD)
      optical detection system intended for time-resolved galvanoluminescence (GL)
      measurements is described. The source has been conceived as a low-cost substitute
      for standard tungsten lamps usually used for relative and absolute calibration of
      optical detection systems. Three LEDs with different spectral characteristics in
      conjunction with a system of two integrating spheres as light mixers and light
      reducers are used. This construction provides control over the source spectrum by
      changing individual LED contributions. The use of integration spheres eliminated
      angular distribution of light intensities of LEDs as well as angular dependence
      of their spectral contributions. Moreover, by using the source we have avoided
      the problem of stray and diffuse light of higher wavelengths, as well as
      different light intensities for different wavelengths (up to three orders of
      magnitude in the range from 400 nm to 750 nm), which we have with standard
      tungsten lamps. A complete calibration procedure for the LED source and ICCD
      detection system is described. Finally, for the first time, we have performed
      time-resolved spectral GL measurements during aluminum anodization in porous film
      forming electrolyte phosphoric acid in a transient regime. Two peaks at 425 nm
      and 595 nm are recognized, confirming the same mechanism of GL in both transient
      and steady-state regimes of anodization.

PMID- 17002838
TI  - Surgical excision of metastatic malignant melanoma involving the tricuspid valve.
AB  - An 83-year-old man presented with a large intracavitatory metastatic malignant
      melanoma, infiltrating the anterior leaflet of the tricuspid valve. The tumour
      was excised completely along with the anterior leaflet of the tricuspid valve
      which was replaced. The patient was well 2 months after surgery.

PMID- 17002839
TI  - Papillary carcinoma in a male breast cyst: a diagnostic challenge.
AB  - Intracystic papillary breast carcinoma is a rare form of non-invasive carcinoma
      with an excellent prognosis. It accounts for less than 0.5% of breast cancers. We
      report the case of a 75-year-old man presenting with a painless cystic lump in
      the right breast. Ultrasonography showed a cystic lesion and aspiration revealed
      blood-stained fluid with suspicion of malignancy. Excisional biopsy was necessary
      to confirm the diagnosis and also indicated that local treatment was adequate.

PMID- 17002840
TI  - Peristomal varices--life threatening or luminal?
AB  - Bleeding from the edge of an ileostomy site is a common problem. In those who
      have undergone a proctocolectomy with ileostomy formation in conjunction with a
      risk of chronic liver disease (even with normal liver function tests), this may
      be due to peristomal varices. If this is the case, significant, difficult-to
      control and potentially life-threatening bleeding is likely in the future and may
      require transfusion. Improvements in radiological imaging techniques can give
      quick, sensitive and specific information to diagnose and guide management in
      this group. In those patients with major bleeding episodes, an initial
      conservative management policy should be adopted with the knowledge that, if
      bleeding persists, propanolol therapy, portosystemic shunt insertion or even
      liver transplantation may be indicated.

PMID- 17002841
TI  - Teaching and assessing surgical competence.
AB  - Surgical competence and its assessment is one of the most hotly debated topics
      engaging the profession. In the current climate of diminishing working hours and
      shorter training, the surgical profession is having to address the complex issue
      as to how surgery as a craft specialty should be taught, and how to assess when
      an individual is competent within their chosen sphere as well as how that
      competence should be maintained. Internationally, there is political pressure
      upon the professional to achieve contracted activity to comply with political
      imperatives and, at the same time, to achieve a greater degree of specialisation.
      Within Europe, the working time directive has led to a shift system of rotas and
      this, along with a shorter overall period of training, has led to reduced time
      available to surgical trainees in which to learn their craft.

PMID- 17002842
TI  - Medullary thyroid carcinoma--update and present management controversies.
AB  - INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy
      arising from the parafollicular C cells. It accounts for 5-10% of thyroid
      malignancies and occurs in sporadic and hereditary forms. There are still many
      controversial aspects relating to the diagnosis and management of this unusual
      tumour in its various forms. The present article addresses the more important of
      these issues. METHODS: A literature review was performed using Pubmed database
      combined with additional original papers obtained from citations in those
      articles identified in the original literature search. Only those articles which
      related specifically to the controversial issues addressed in this review were
      included. RESULTS: Genetically determined tumours constitute approximately 25% of
      MTC and have special clinical interest because of their association with other
      endocrinopathies including phaeochromocytoma and hyperparathyroidism in the
      multiple endocrine neoplasia syndromes (MEN IIa and MEN IIb). Familial medullary
      thyroid carcinoma (FMTC) is a rare form not associated with any other
      endocrinopathies. The genetic basis for these familial tumours derives from a
      series of missense germline mutations in the RET protooncogene. Genetic testing
      by DNA analysis facilitates identification of family members at risk who can now
      be offered early 'prophylactic thyroidectomy' with an increased prospect of
      surgical success and long-term survival. MTC is a tumour which does not take up
      radioactive iodine, is relatively radioresistant and poorly responsive to
      chemotherapy. Therefore, surgery is the only treatment which can offer the
      prospect of cure. Total thyroidectomy with central and lateral nodal dissection
      can achieve biochemical cure (normocalcitonaemia) in more than 80% of cases.
      Compartmental orientated microdissection of cervical nodes has significantly
      improved the results of primary surgery but even so a group of 20% of patients
      will prove to have recurrent or residual disease. These cases require detailed
      investigation by a variety of techniques including ultrasound, cross-sectional
      imaging, nuclear imaging and laparoscopy with liver biopsy to exclude
      disseminated disease and select those patients who can be offered a prospect of
      cure by further neck surgery. Such an approach may be associated with successful
      normalisation of calcitonin levels in about 40%. CONCLUSIONS: It is hoped that in
      the near future new medical therapies may become available to treat MTC which
      still has a 10-year survival of only 60-80% in spite of the application of
      meticulous surgical techniques.

PMID- 17002843
TI  - Prostate cancer treatment. The case for radical prostatectomy.

PMID- 17002845
TI  - A colorectal cancer patient focus group develops an information package.
AB  - INTRODUCTION: In order to deliver high quality care and empower cancer patients
      in decision-making, good quality information and communication are essential. We
      describe the development of an information booklet. PATIENTS AND METHODS: A total
      of 22 colorectal cancer patients (12 male; median age, 72 years, range, 40-86
      years) met on 3 occasions. Patients were asked to define their information needs
      and score them (1-4) according to importance. The information document was
      written. The second meeting involved feedback on the booklet. The modified
      booklet was reviewed/approved by the group before submission for local ethics
      committee approval prior to its distribution to other patients. RESULTS: All
      participants felt the project a good idea. Essential information included the
      surgeon's individual morbidity, mortality, survival, recurrence data and details
      of adjuvant therapies (score = 4). Also important were type of surgery,
      complications and postoperative recovery (score = 3). Simple anatomical drawings
      were also considered important. CONCLUSIONS: The booklet is now used to
      personalise information for all our patients and serves, in part, as a record of
      the key issues discussed during the consultation. The booklet has been evaluated
      in a randomised trial.

PMID- 17002846
TI  - Training opportunities in the management of paediatric fractures: a district
      general hospital perspective.
AB  - INTRODUCTION: Increasing subspecialisation, the introduction of reforms to
      surgical training, centralisation of hospitals and the reduction of working hours
      brought about by the European Working Time Directive (EWTD) has direct
      implications on the training of surgeons in the UK. The aim of this study was to
      determine the range and number of procedures performed for paediatric orthopaedic
      fractures, degree of supervision and possible implications for training. PATIENTS
      AND METHODS: A retrospective review of procedures for paediatric orthopaedic
      fractures performed in a district general hospital in a year was conducted.
      RESULTS: A total of 210 paediatric fracture procedures were performed, including
      99 distal radius/ulna procedures, 28 shaft radius/ulna, 25 supracondylar
      procedures, 15 hand fracture procedures, 14 tibial shaft procedures. Middle
      grade/registrars and senior house officers performed 188 (89.5%) of all
      procedures. Consultant supervision was documented in 29 (13.8%) of all procedures
      performed. The number and type of common, as well as unusual, injuries was
      documented. The educational value of a training post may only be confirmed by
      reliable data which would provide an indication of operative opportunities and
      degree of supervision available to a trainee. CONCLUSIONS: This study provided a
      model upon which all operative training opportunities in the orthopaedic
      department is documented. It is suggested that such data should form the basis of
      the establishment of training posts within a region. To maintain the high
      standard of orthopaedic training in the UK, the maintenance of such posts, number
      of trainees and seniority of trainees appointed to any hospital within a training
      region should be on the basis of data such as reported in this study.

PMID- 17002847
TI  - Response to: A prospective audit of 300 consecutive young women with an acute
      presentation of right iliac fossa pain.

PMID- 17002848
TI  - Response to: Is patient care affected by the recent changes in junior doctors'
      training?

PMID- 17002849
TI  - Survey of the management of acute traumatic first-time anterior shoulder
      dislocation among trauma clinicians in the UK.
AB  - INTRODUCTION: The aim of this work was to survey how acute traumatic first-time
      anterior shoulder dislocation (AFSD) is managed among trauma clinicians in UK
      using a postal questionnaire. PATIENTS AND METHODS: A total of 150 questionnaires
      were sent out to active consultant members of the British Trauma Society in the
      UK. Questions were laid out in two 'workgroups'. In Workgroup One, an assortment
      of questions was included regarding choices and methods of analgesia, methods of
      monitoring used, methods of reduction, and position of immobilisation. In
      Workgroup Two, three different case scenarios were analysed to look into the
      'post-reduction' management. RESULTS: The response rate was 60%. Of respondents,
      22% have a local protocol for managing AFSD. Almost all respondents recommended
      pre- and post-reduction X-rays as standard practice. Most respondents favoured
      systemic analgesia and sedation with airways' monitoring, as opposed to intra
      articular anaesthesia (68 versus 9). Eighty-four respondents advocated
      immobilisation in internal rotation compared to six in external rotation. Only
      19% (16 of 84) of respondents would perform an immediate arthroscopic
      stabilisation in young, fit patients presenting with this type of injury.
      CONCLUSIONS: This survey revealed variations among trauma clinicians in managing
      AFSD on the 'front-line'. There is a need to address the issue of intra-articular
      analgesia, immobilisation technique and management of AFSD in the young patient
      with regards to immediate surgical intervention. We suggest that these issues be
      revised and clarified, ideally in a randomised, controlled, clinical trial prior
      to the introduction of a protocol for managing this problem.

PMID- 17002850
TI  - Role of gymnastics in the Army School of Physical Training.
AB  - INTRODUCTION: As a result of a single spinal injury seen at Frimley Park
      Hospital, we reviewed the injuries recorded at the Army School of Physical
      Training since December 1996. PATIENTS AND METHODS: This was a retrospective
      review of all acute accidents and injuries recorded in the Accident Book since
      its inception. RESULTS: Over 75% of the injuries that were serious enough to
      result in soldiers having their training terminated were as a direct result of
      gymnastic events such as vaulting, trampolining and somersaults. These events
      were also responsible for most of the small number of career-threatening
      injuries. CONCLUSIONS: This raises questions about the inclusion of gymnastic
      events in course training programmes, especially when considering its relevance
      to army training in general.

PMID- 17002851
TI  - Forgotten digital tourniquet: salvage of an ischaemic finger by application of
      medicinal leeches.
AB  - Individual finger tourniquets are appropriate to the management of a wide range
      of conditions presenting to an accident and emergency department. They are
      simpler and more comfortable to use than upper arm pneumatic tourniquets and
      commercially available digital tourniquets are not readily available in the
      accident and emergency unit. However, if a finger tourniquet is overlooked,
      ischaemia of the digit results, and gangrene may follow if the problem is not
      defused early enough, leading to potential disaster. We present one case where a
      digit was salvaged after 4 days of tourniquet application, using medicinal
      leeches.

PMID- 17002852
TI  - Comfort assessment of personal protection systems during total joint arthroplasty
      using a novel multi-dimensional evaluation tool.
AB  - INTRODUCTION: A number of studies have assessed the usefulness of surgical gowns
      and exhaust suits with regards to barrier function and protection afforded to
      healthcare workers from blood strike-through, splashes and aerosols. PATIENTS AND
      METHODS: We have performed a comfort assessment comparison between the Charnley
      exhaust suit, disposable gown plus visor and the Stryker Steri-Shield system
      using a newly developed objective multidimensional ergonomic tool designed to
      measure wearable comfort across the dimensions of emotion, attachment, harm,
      perceived change, movement and anxiety. RESULTS: The total mean Comfort Rating
      Scale value for a disposable gown plus visor was 16.1 with a mean dimensional
      score of 2.7 (range, 0.2-8.4), for the Charnley system the values were 51.4 and
      8.6 (range, 5.9-12.8), respectively, and for the Stryker Steri-Shield 15.4 and
      2.6 (range, 0.8-5.6). CONCLUSIONS: The Steri-Shield system provides the least
      variation in comfort and, as such, may offer the best combination of comfort,
      protective qualities and form or style of personal protection equipment for lower
      limb arthroplasty operations.

PMID- 17002853
TI  - Secondary prevention of fragility fractures: are we following the guidelines?
      Closing the audit loop.
AB  - INTRODUCTION: The aim of this study was to determine whether orthopaedic surgeons
      follow the British Orthopaedic Association (BOA) guidelines for secondary
      prevention of fragility fractures. PATIENTS AND METHODS: A retrospective audit
      was conducted on patients with neck of femur fractures treated in our hospital
      between October and November 2003. A re-audit was conducted during the period
      August to October 2004. RESULTS: There were 27 patients in the initial study
      period. Twenty-six patients (96%)had full blood count measured with LFT and bone
      profile measured in 18 patients (66%). Only nine patients (30%)had treatment for
      osteoporosis (calcium and vitamin D). Only one patient was referred for DEXA
      scan. Steps were taken in the form of creating better awareness among the junior
      doctors and nurse practitioners of the BOA guidelines. In patients above 80 years
      of age, it was decided to use abbreviated mental score above 7 as a clinical
      criteria for DEXA referral. A hospital protocol based on BOA guidelines was made.
      A re-audit was conducted during the period August to October 2004. There were 37
      patients. All had their full blood count and renal profile checked (100%). The
      bone-profile was measured in 28 (75.7%) and LFT in 34 (91.9%) patients. Twenty
      four patients (65%) received treatment in the form of calcium + vitamin D (20)
      and bisphosphonate (4). DEXA-scan referral was not indicated in 14 patients as 4
      were already on bisphosphonates and for 10 patients their abbreviated mental
      score was less than 7. Among the remaining 23 patients, 9 patients (40%) were
      referred for DEXA scan. This improvement is statistically significant (P = 0.03,
      chi square test). DISCUSSION AND CONCLUSIONS: The re-audit shows that, although
      there is an improvement in the situation, we are still below the standards of
      secondary prevention of fragility fractures with 60% of femoral fragility
      fracture patients not being referred for DEXA scan. A pathway lead by a fracture
      liaison nurse dedicated to osteoporotic fracture patients should improve the
      situation.

PMID- 17002854
TI  - Re-admission rates within 28 days of total hip replacement.
AB  - INTRODUCTION: The aim of the study was to identify the reasons for the higher
      than expected emergency re-admission to hospital within 28 days of total hip
      replacement (THR) for Stepping Hill Hospital, Stockport. PATIENTS AND METHODS:
      Over a 42-month period, 65 (8.5%) of 769 patients were re-admitted within 28 days
      of discharge following primary THR. Case notes for 61 patients were available for
      retrospective review to assess premorbidity, initial postoperative complications
      and reason for re-admission. RESULTS: The main reasons for re-admission were
      complications related to the procedure. These included thrombo-embolic disease
      2.5%, atraumatic dislocation 1.4%, wound complications 1.2% and swollen limb
      1.8%. Other causes such as admission to another department for problems not
      related to THR accounted for 0.8%. CONCLUSIONS: Our findings are comparable with
      the published literature for early complications following THR. The three main
      reasons for re-admission were atraumatic dislocation, thrombo-embolic and wound
      complications such as superficial infection and haematoma are the commonest world
      wide. The re-admission rate to hospital within the first 28 days following THR
      was a clinical indicator suggested by the UK Department of Health. It has
      subsequently been incorporated in a group of indicators used by the CASPE
      Healthcare Knowledge Systems (CHKS), a private healthcare consultancy and
      analysis company, for peer benchmarking. Our re-admission rates are inflated by
      admissions for non-THR-related reasons. The level of post-THR complications
      leading to re-admission were acceptable compared with the available published
      literature regarding 28-day re-admission. We anticipate that this study may act
      as a benchmark for other trusts.

PMID- 17002855
TI  - Contamination and decontamination of Doppler probes.
AB  - INTRODUCTION: Nosocomial infection occurs in 2-9% of patients undergoing vascular
      surgery and can lead to death, amputation or require complex revision surgery.
      Neck ties, pagers, stethoscopes and Doppler probes have been shown to carry
      pathogens. We measured bacterial colonisation of Doppler probes on a vascular
      unit and audited the effect of staff education at reducing this contamination.
      MATERIALS AND METHODS: Bacteriological culture swabs were taken from hand-held
      Doppler probes on the vascular surgical ward and clinic. There was no protocol
      for cleaning the Doppler probes, so manufacturers were contacted for their
      recommendations. The results of cultures were presented to nursing and medical
      staff, who were then asked to clean the probes with alcohol wipes after each use.
      After an interval of 1 week, bacteriological cultures from the same Doppler
      probes was repeated. RESULTS: Fifty bacteriological cultures were performed from
      10 Doppler probes over a 4-week period. Thirteen (26%) cultures were positive for
      diphtheroids, coliforms, coagulase-negative staphylococci and skin flora. After
      staff education, 42 further swabs were taken from the same probes; two positive
      cultures were obtained with scanty growth of skin flora (chi2 P < 0.05).
      CONCLUSIONS: Staff education and simple cleaning significantly reduces the
      contamination of hand-held Doppler probes and may help prevent nosocomial
      infection.

PMID- 17002856
TI  - Variations in consenting practice for laparoscopic cholecystectomy.
AB  - INTRODUCTION: To compare the variations in consenting practice amongst trainees
      and consultant surgeons for laparoscopic cholecystectomy with specific reference
      to the documentation of significant risks of surgery. PATIENTS AND METHODS: A
      proforma was devised which included significant and/or commonly recognised
      complications of laparoscopic cholecystectomy. This was then cross-referenced
      with the consent forms for the 80 patients included in the study and the
      documented risks explained in each case were noted. RESULTS: The results showed
      that there is considerable variation between the three grades of clinicians
      involved in obtaining a patient's consent for laparoscopic cholecystectomy. There
      was a clear difference in emphasis of the significant complications depending on
      the seniority of the consenter. Over 80% of the consents in this study were still
      being obtained by junior staff. CONCLUSIONS: More often than not, patients are
      not provided with consistent information to make an informed choice. We suggest
      that a preprinted consent form will provide a more uniform approach to consenting
      practice for laparoscopic cholecystectomy.

PMID- 17002857
TI  - Setting the standard--UK neurosurgical acoustic neuroma practice.
AB  - INTRODUCTION: The aim of this study was to determine how current practice in the
      UK and Ireland complies with the Clinical Effectiveness Guidelines for the
      Management of Acoustic Neuromas. MATERIALS AND METHODS: A survey of units and
      consultants using a standardised questionnaire was carried out. RESULTS: Fifty
      six neurosurgeons treat acoustic neuromas in 33 out of 34 units. In 27 units, one
      or two surgeons specialise in this area. Caseload per annum per surgeon ranged
      from 2 to 30, median 15. Forty-one neurosurgeons (75%) work with an ENT surgeon.
      All surgeons use facial nerve monitoring during surgery. All neurosurgeons
      informed patients about stereotactic radiosurgery, tending to recommend it for
      medically unfit patients, and those with small tumours. CONCLUSIONS: Overall, 26
      units (79%) and 40 surgeons (73%) met the criteria for good surgical practice.
      The main reasons for non-compliance were a lack of teamwork with ENT, and
      insufficient caseload to maintain surgical expertise.

PMID- 17002858
TI  - Vestibular schwannoma management: current practice amongst UK otolaryngologists-
      time for a national prospective audit.
AB  - INTRODUCTION: It is generally agreed that the successful management of a
      vestibular schwannoma (VS) usually involves close collaboration between a neuro
      otologist and neurosurgeon. In addition, it is accepted that the experience of
      the team managing such tumours is one of the key determinants of outcome after
      surgical intervention. The aim of this study was to identify current practice in
      the management of such tumours amongst otolaryngologists in the UK and to observe
      whether such collaborative working practices exist. MATERIALS AND METHODS: A
      cross sectional postal questionnaire survey of consultant members of the British
      Association of Otorhinolaryngologists-Head and Neck Surgeons (n = 542). RESULTS:
      A total of 336 replies were received (62%). Of respondents, 299 consultants
      referred their patients to another surgeon for further management; 242 referred
      to another ENT surgeon (80.9%), 29 to a neurosurgeon (9.7%) and 28 to a combined
      team (9.4%). Twenty-eight of the responding otolaryngologists (8.6%) managed the
      tumours themselves, of whom 22 worked with a neurosurgeon. Of these 28 neuro
      otologists, nearly two-thirds (64%) had been undertaking VS surgery for more than
      10 years. The total number of patients with a VS referred to these 28 consultants
      during 2001 was 775, with a mean caseload of 29.8, median 23 and a range of 4 to
      102 per surgeon. Seven of the 28 otolaryngologists chose their surgical approach
      entirely based on the size of the tumour. Eight consultants preferred the sub
      occipital (SO) approach, 10 the translabyrinthine (TL) approach, three chose
      between SO and TL approaches. The majority of surgeons had a prospective,
      computer-based data collection and were willing to give further information about
      their outcomes and complications. CONCLUSIONS: Amongst the otolaryngologists
      surveyed in the UK, we have identified 28 neuro-otologists who undertake VS
      surgery. The majority work with neurosurgical colleagues, confirming
      collaborative practice. The wide range in caseload raises the issue of training
      and maintaining standards and in the first instance we recommend a prospective
      national audit of VS management and outcomes with our neurosurgical colleagues.
      This would also be of value in manpower planning particularly if a minimum
      caseload could be identified below which results were seen to be less good.

PMID- 17002859
TI  - Urethral dilatation in women: urologists' practice patterns in the UK.
AB  - INTRODUCTION: Review of the literature reveals little evidence to prove the
      efficacy of urethral dilatation for adult women with various lower urinary tract
      complaints. We conducted a postal survey to ascertain the actual practice of
      urethral dilatation among urologists in the UK. MATERIALS AND METHODS: A
      questionnaire was mailed to 428 consultant urologists listed as full members of
      the British Association of Urological Surgeons. The questionnaire consisted of 8
      items about urologists' perception of indications, efficacy, and the need for
      repeated dilatation and anaesthesia. RESULTS: The questionnaire response rate was
      42%. Although urethral stenosis was the most common indication (97%), the
      majority of urologists (69%) indicated that fewer than 25% of patients had
      evidence of stenosis. Overall, 61% of urologists performed dilatation 7 times or
      more during the last year and 55% believed that less than half of the patients
      experienced long-term improvement. CONCLUSIONS: Despite the lack of strong
      evidence to support the use of urethral dilatation in women, many urologists
      continue to find it a useful tool in approaching women with lower urinary tract
      complaints.

PMID- 17002861
TI  - Comment on: Alternate nail cleaners.

PMID- 17002862
TI  - Comments on: Increase in septic pathology is associated with increase in HIV
      seroprevalence.

PMID- 17002863
TI  - Comments on: Role of bone scintigraphy.

PMID- 17002864
TI  - Comments on: Multidetector row computed tomography.

PMID- 17002865
TI  - Comment on: Unsuccessful use of syringe as a drill sleeve.

PMID- 17002866
TI  - Differential roles of vascular endothelial growth factor receptor-1 and receptor
      2 in angiogenesis.
AB  - Vascular endothelial growth factor (VEGF)-A, a major regulator for angiogenesis,
      binds and activates two tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2
      (KDR/Flk-1). These receptors regulate physiological as well as pathological
      angiogenesis. VEGFR2 has strong tyrosine kinase activity, and transduces the
      major signals for angiogenesis. However, unlike other representative tyrosine
      kinase receptors which use the Ras pathway, VEGFR2 mostly uses the Phospholipase
      Cgamma-Protein kinase-C pathway to activate MAP-kinase and DNA synthesis. VEGFR2
      is a direct signal transducer for pathological angiogenesis including cancer and
      diabetic retinopathy, thus, VEGFR2 itself and the signaling appear to be critical
      targets for the suppression of these diseases. VEGFR1 plays dual role, a negative
      role in angiogenesis in the embryo most likely by trapping VEGF-A, and a positive
      role in adulthood in a tyrosine kinase-dependent manner. VEGFR1 is expressed not
      only in endothelial cells but also in macrophage-lineage cells, and promotes
      tumor growth, metastasis, and inflammation. Furthermore, a soluble form of VEGFR1
      was found to be present at abnormally high levels in the serum of preeclampsia
      patients, and induces proteinurea and renal dysfunction. Therefore, VEGFR1 is
      also an important target in the treatment of human diseases. Recently, the VEGFR2
      specific ligand VEGF-E (Orf-VEGF) was extensively characterized. Interestingly,
      the activation of VEGFR2 via VEGF-E in vivo results in a strong angiogenic
      response in mice with minor side effects such as inflammation compared with VEGF
      A, suggesting VEGF-E to be a novel material for pro-angiogenic therapy.

PMID- 17002867
TI  - Heme oxygenase-1 as a potential therapeutic target for hepatoprotection.
AB  - Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into
      carbon monoxide (CO), iron and bilirubin, has recently received overwhelming
      research attention. To date three mammalian HO isozymes have been identified, and
      the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed.
      Advances in unveiling signal transduction network indicate that a battery of
      redox-sensitive transcription factors, such as activator protein-1 (AP-1),
      nuclear factor-kappa B (NF-kappaB) and nuclear factor E2-related factor-2 (Nrf2),
      and their upstream kinases including mitogen-activated protein kinases play an
      important regulatory role in HO-1 gene induction. The products of the HO
      catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to
      exert protective effects in several organs against oxidative and other noxious
      stimuli. In this context, it is interesting to note that induction of HO-1
      expression contributes to protection against liver damage induced by several
      chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals,
      suggesting HO-1 induction as an important cellular endeavor for hepatoprotection.
      The focus of this review is on the significance of targeted induction of HO-1 as
      a potential therapeutic strategy to protect against chemically-induced liver
      injury as well as hepatocarcinogenesis.

PMID- 17002868
TI  - GTP induces S-phase cell-cycle arrest and inhibits DNA synthesis in K562 cells
      but not in normal human peripheral lymphocytes.
AB  - Since differentiation therapy is one of the promising strategies for treatment of
      leukemia, universal efforts have been focused on finding new differentiating
      agents. In that respect, we used guanosine 5'-triphosphate (GTP) to study its
      effects on K562 cell line. GTP, at concentrations between 25-200 microM,
      inhibited proliferation (3-90%) and induced 5-78% increase in benzidine-positive
      cells after 6-days of treatments of K562 cells. Flow cytometric analyses of
      glycophorine A (GPA) showed that GTP can induce expression of this marker in more
      mature erythroid cells in a time- and dose-dependent manner. These effects of GTP
      were also accompanied with inhibition of DNA synthesis (measured by [3H]
      thymidine incorporation) and early S-phase cell cycle arrest by 96 h of exposure.
      In contrast, no detectable effects were observed when GTP administered to
      unstimulated human peripheral blood lymphocytes (PBL). However, GTP induced an
      increase in proliferation, DNA synthesis and viability of mitogen-stimulated PBL
      cells. In addition, growth inhibition and differentiating effects of GTP were
      also induced by its corresponding nucleotides GDP, GMP and guanosine (Guo). In
      heat-inactivated medium, where rapid degradation of GTP via extracellular
      nucleotidases is slow, the anti-proliferative and differentiating effects of all
      type of guanine nucleotides (except Guo) were significantly decreased. Moreover,
      adenosine, as an inhibitor of Guo transporter system, markedly reduced the GTP
      effects in K562 cells, suggesting that the extracellular degradation of GTP or
      its final conversion to Guo may account for the mechanism of GTP effects. This
      view is further supported by the fact that GTP and Guo are both capable of
      impeding the effects of mycophenolic acid. In conclusion, our data will hopefully
      have important impact on pharmaceutical evaluation of guanine nucleotides for
      leukemia treatments.

PMID- 17002869
TI  - Molecular cloning, characterization and functional analysis of a 2C-methyl- D
      erythritol 2, 4-cyclodiphosphate synthase gene from ginkgo biloba.
AB  - 2C-methyl-D-erythritol 2, 4-cyclodiphosphate synthase (MECPS, EC: 4.6.1.12) is
      the fifth enzyme of the non-mevalonate terpenoid pathway for isopentenyl
      diphosphate biosynthesis and is involved in the methylerythritol phosphate (MEP)
      pathway for ginkgolide biosynthesis. The full-length mecps cDNA sequence
      (designated as Gbmecps) was cloned and characterized for the first time from
      gymnosperm plant species, Ginkgo biloba, using RACE (rapid amplification of cDNA
      ends) technique. The full-length cDNA of Gbmecps was 874 bp containing a 720 bp
      open reading frame (ORF) encoding a peptide of 239 amino acids with a calculated
      molecular mass of 26.03 kDa and an isoelectric point of 8.83. Comparative and
      bioinformatic analyses revealed that GbMECPS showed extensive homology with
      MECPSs from other species and contained conserved residues owned by the MECPS
      protein family. Phylogenetic analysis indicated that GbMECPS was more ancient
      than other plant MECPSs. Tissue expression pattern analysis indicated that
      GbMECPS expressed the highest in roots, followed by in leaves, and the lowest in
      seeds. The color complementation assay indicated that GbMECPS could accelerate
      the accumulation of beta-carotene. The cloning, characterization and functional
      analysis of GbMECPS will be helpful to understand more about the role of MECPS
      involved in the ginkgolides biosynthesis at the molecular level.

PMID- 17002870
TI  - Alanine aminotransferase in amphioxus: Presence, localization and up-regulation
      after acute lipopolysaccharide exposure.
AB  - Alanine aminotransferase (AAT) is mainly synthesized in the liver, and its level
      in mammalian serum is elevated after acute phase induction. Here we demonstrated
      that sheep anti-human AAT antibody cross-reacted with amphioxus humoral fluids as
      well as human serum; and the concentration of AAT in the humoral fluids in
      amphioxus increased after the acute challenge with lipopolysaccharide, while the
      level of total proteins remains unchanged. These suggest the presence of the same
      acute phase response pattern in amphioxus, as observed in some mammalian species.
      Immunohistochemically, AAT was localized in the hepatic diverticulum, ovary and
      testis. It appears that the hepatic diverticulum in amphioxus is functionally
      homologous to the vertebrate liver in respect of AAT synthesis, supporting the
      hypothesis that the vertebrate liver evolved from the hepatic diverticulum of an
      amphioxus-like ancestor during early chordate evolution.

PMID- 17002871
TI  - Determination of saturated and unsaturated Fatty acids amount in leukocyte
      membranes from subjects fed with solid and fluid oils.
AB  - Modifications in dietary fatty acid intake might lead to a modification in
      membrane phospholipid fatty acid composition. The purpose of this study was to
      investigate relationship between different type of oil consumption and leukocyte
      membrane phospholipid composition. This study was carried out in subjects
      utilizing butter (n = 15), margarine (n = 15), fluid oil (n = 15) and mixed types
      of oils (n = 15) in total 60 subjects. Leukocytes were separated from total blood
      by dextran sedimentation method. Membrane lipids and proteins were isolated
      following the cell disruption. Fatty acids of membrane phospholipids were
      isolated by hydrolysation with phospholipase B under ultrasonic dismembranator.
      Free fatty acids were identified with gas chromatography at chloroform phase. The
      results obtained were compared with data obtained by chromatograms of the
      standards. Results more prominent values of arachidic, dihomo-gamma-linolenic and
      palmitoleic acids were found in butter-or mixed oil-user groups; eicosadienoic,
      eicosamonoenoic, dihomo-gamma-linolenic and behenic acids in fluid oil heptanoic,
      valeric, eicosadienoic and linolenic acids in margarine groups. The fatty acid
      composition of mixed oil; was similar to butter, while other two oils were so
      different. From this study, it was concluded that the type of oil consumption
      might have an influence on phospholipid components of plasma membranes.

PMID- 17002872
TI  - Molecular phylogeny of silk producing insects based on internal transcribed
      spacer DNA1.
AB  - Silk moths are the best studied silk secreting insects and belong to the families
      Bombycidae and Saturniidae. The phylogenetic relationship between eleven silk
      producing insects was analyzed using the complete DNA sequence of the internal
      transcribed spacer DNA 1 locus. The PCR amplification and sequence analysis
      showed variation in length ranging from 138 bp (Antheraea polyphemus) to 911 bp
      (Hyalopora cecropia). Microsatellite sequences were found and was be used to
      distinguish Saturniidae and Bombycidae members. The nucleotide sequences were
      aligned manually and used for construction of phylogenetic trees based on Maximum
      parsimony and Maximum likelihood methods. The topology in both the approaches
      yielded a similar tree that supports the ancestral position of the Antheraea
      assama.

PMID- 17002873
TI  - Conformational study of human serum albumin in pre-denaturation temperatures by
      differential scanning calorimetry, circular dichroism and UV spectroscopy.
AB  - Thermal conformational changes of human serum albumin (HSA) in phosphate buffer,
      10 mM at pH = 7 are investigated using differential scanning calorimetric (DSC),
      circular dichroism (CD) and UV spectroscopic methods. The results indicate that
      temperature increment from 25 degrees C to 55 degrees C induces reversible
      conformational changes in the structure of HSA. Conformational change of HSA are
      shown to be a three-step process. Interestingly, melting temperature of the last
      domain is equal to the maximum value of fever in pathological conditions, i.e. 42
      degrees C. These conformational alterations are accompanied by a mild alteration
      of secondary structures. Study of HSA-SDS (sodium dodecyl sulphate) interaction
      at 45 degrees C and 35 degrees C reveals that SDS affects the HSA structure at
      least in three steps: the first two steps result in more stabilization and
      compactness of HSA structure, while the last one induces the unfolding of HSA.
      Since HSA has a more affinity for SDS at 45 degrees C compared to 35 degrees C,
      It is suggested that the net negative charge of HSA is decreased in fever, which
      results in the decrease of HSA-associated cations and plasma osmolarity, and
      consequently, heat removal via the increase in urine volume.

PMID- 17002874
TI  - Characterization and expression profile of CMTM3/CKLFSF3.
AB  - CMTM/CKLFSF is a novel family of proteins linking chemokines and TM4SF. In
      humans, these proteins are encoded by nine genes, CKLF and CMTM1-8/CKLFSF1-8.
      Here we report the characteristics and expression profile of CMTM3/CKLFSF3. Human
      CMTM3/CKLFSF3 has a high sequence identity among various species and similar
      characteristics as its mouse and rat homologues. Established by results both of
      RT-PCR and Quantitative Real-time PCR, the gene is highly transcribed in testis,
      leukocytes and spleen. For further verification, we generated a polyclonal
      antibody against human CMTM3/CKLFSF3 and found that the protein is highly
      expressed in the testis and some cells of PBMCs. Therefore, CMTM3/CKLFSF3 is an
      evolutionarily conserved gene that may have important roles in the male
      reproductive system and immune system. Further studies are necessary to validate
      its functions in the two systems.

PMID- 17002875
TI  - Purification and partial characterization of an acidic polysaccharide with
      complement fixing ability from the stems of Avicennia marina.
AB  - An acidic polysaccharide fraction that had high anticomplementary activity was
      isolated from the stems of Grey Mangrove in 0.15% yield. The final fractions was
      designated HAM-3-IIb-II. The polysaccharide fraction appeared to be homogenous by
      high performance size exclusion chromatography with an estimated molecular weight
      of 105 kDa. The isolated polysaccharide is more effective than polysaccharide K
      (PSK) in its anticomplementary activity at 58 microg/ml of PSK and 23 microg/ml
      of HAM-3-IIb-II that inhibit 50% of complement activity in the complement
      fixation assay. Structural studies indicated that HAM-3-IIb-II was rich in
      galacturonic acid along with arabinose, galactose and rhamnose, characterizing a
      pectin-type polysaccharide, which was also confirmed by FT-IR spectrum. The
      presence of rich neutral sugar side chains of arabinogalactans may have
      contributed to the expression of high activity. Traditionally, this mangrove
      plant is used for medicinal purposes and it appears to have some scientific
      applications.

PMID- 17002876
TI  - Differential efflux of mitochondrial endonuclease G by hNoxa and tBid.
AB  - The Bcl-2 family of proteins regulates mitochondrial functions during cell death
      by modulating the efflux of death-promoting proteins such as cytochrome c and
      endonuclease G. Upon the binding of death ligands to their receptors, caspase-8
      cleaves Bid, a BH3-only protein, into tBid that causes the mitochondrial damages
      resulting in the release of cytochrome c and endonuclease G. Also, another BH3
      only protein, hNoxa, has been shown to induce the efflux of cytochrome c from the
      mitochondria. Whether the efflux proteins from the mitochondria in response to
      tBid or hNoxa are the same or different, however, has not been addressed. We have
      demonstrated that endonuclease G activities are not detectable among the proteins
      released from isolated mitochondria by hNoxa but are detectable in that by tBid.
      These results suggest that the efflux of proteins from the mitochondria are
      differentially modulated by tBid and hNoxa.

PMID- 17002877
TI  - Molecular characterization of the recombinant A-chain of a type II ribosome
      inactivating protein (RIP) from Viscum album coloratum and structural basis on
      its ribosome-inactivating activity and the sugar-binding properties of the B
      chain.
AB  - Mistletoe (Viscum album) lectins, which are classified as a type II ribosome
      inactivating protein (RIP) due to their unique biological function and the
      potential medical and therapeutic application in cancer cells, receive a rising
      attention. The heterodimeric glycoproteins contain the Achain with catalytic
      activity and the B-chain with sugar binding properties. In recent years, studies
      involving the lectins from the white berry European mistletoe (Viscum album) and
      the yellow berry Korean mistletoe (Viscum album coloratum) have been described.
      However, the detailed mechanism in exerting unique cytotoxic effect on cancer
      cells still remains unclear. Here, we aim to understand and define the molecular
      basis and biological effects of the type II RIPs, through the studies of the
      recombinant Korean mistletoe lectin. To this end, we expressed, purified the
      recombinant Korean mistletoe lectin (rKML), and investigated its molecular
      characteristics in vitro, its cytotoxicity and ability to induce apoptotic cell
      death in cancer cells. To gain structural basis for its catalytic activity and
      sugar binding properties, we performed homology modeling studies based on the
      high degree of sequence identity and conserved secondary structure prediction
      between Korean and European, Himalayan mistletoe lectins, and Ricin.

PMID- 17002878
TI  - Expression and characterization of RNA-dependent RNA polymerase of Dendrolimus
      punctatus tetravirus.
AB  - Dendrolimus punctatus tetravirus (DpTV) has been identified as a new member of
      the genus Omegatetravirus of the family Tetraviridae that may be related
      serologically to Nudaurelia capensis virus (NomegaV). To establish the function
      of DpTV RNA genome and to better understand the mechanism of viral replication,
      the putative RNA-dependent RNA polymerase (RdRp) domain has been cloned and
      expressed in Escherichia coli. The recombinant protein was purified on a Ni
      chelating HisTrap affinity column and demonstrated to initiate viral RNA
      synthesis in a primer-independent manner but not by terminal nucleotidyle
      transferase activity in the presence of Mg2+ and RNA template. Mutation of the
      GDD to GAA interferes with the residues at the polymerase active site and metal
      ions, and thus renders the polymerase inactive.

PMID- 17002879
TI  - cDNA cloning, expression and homology modeling of a luciferase from the firefly
      Lampyroidea maculata.
AB  - The cDNA of a firefly luciferase from lantern mRNA of Lampyroidea maculata has
      been cloned, sequenced and functionally expressed. The cDNA has an open reading
      frame of 1647 bp and codes for a 548-residue-long polypeptide. Noteworthy,
      sequence comparison as well as homology modeling showed the highest degree of
      similarity with H. unmunsana and L. mingrelica luciferases, suggesting a close
      phylogenetic relationship despite the geographical distance separation. The
      deduced amino acid sequence of the luciferase gene of firefly L. maculata showed
      93% identity to H. unmunsana. Superposition of the three-dimensional model of L.
      maculata luciferase (generated by homology modeling) and three dimensional
      structure of Photinus pyralis luciferase revealed that the spatial arrangements
      of Luciferin and ATP-binding residues are very similar. Putative signature of
      AMPbinding domain among the various firefly species and Lampyroidea maculata was
      compared and a striking similarity was found. Different motifs and sites have
      been identified in Lampyroidea maculata by sequence analysis. Expression and
      purification of luciferase from Lampyroidea maculata was carried out using Ni-NTA
      Sepharose. Bioluminescence emission spectrum was similar to Photinus pyralis
      luciferase.

PMID- 17002880
TI  - Germinal center-independent affinity maturation in tumor necrosis factor receptor
      1-deficient mice.
AB  - Germinal centers (GCs) have been identified as site at which the somatic mutation
      of immunoglobulins occurs.However, somatic mutations in immunoglobulins have also
      been observed in animals that normally do not harbor germinal centers. This
      clearly indicates that somatic mutations can occur in the absence of germinal
      centers. We therefore attempted to determine whether or not GCs exist in TNFR1
      deficient mice, and are essential for the somatic mutation of immunoglobulins,
      using (4-hydroxy-3-nitropheny)acetyl-ovalbumin (NP-OVA). Both wild-type and TNFR1
      deficient mice were immunized with NPOVA, and then examined with regard to the
      existence of GCs. No typical B-cell follicles were detected in the TNFR1
      deficient mice. Cell proliferation was detected throughout all splenic tissue
      types, and no in vivo immunecomplex retention was observed in the TNFR1-deficient
      mice. All of these data strongly suggest that no GCs were formed in the TNFR1
      deficient mice. Although TNFR1-deficient mice are unable to form GCs, serological
      analyses indicated that affinity maturation had been achieved in both the wild
      type and TNFR1-deficient mice. We therefore isolated and sequenced several DNA
      clones from wild-type and the TNFR1-deficient mice. Eight out of 12 wild-type
      clones, and 11 out of 14 clones of the TNFR-1-deficient mice contained mutations
      at the CDR1 site. Thus, the wild-type and TNFR1-deficient mice were not extremely
      different with regard to types and rates of somatic mutation. Also, high-affinity
      antibodies were detected in both types of mice. Collectively, our data appear to
      show that affinity maturation may occur in TNFR1-deficient mice, which completely
      lack GCs.

PMID- 17002881
TI  - Molecular analyses of the metallothionein gene family in rice (Oryza sativa L.).
AB  - Metallothioneins are a group of low molecular mass and cysteine-rich metal
      binding proteins, ubiquitously found in most living organisms. They play an
      important role in maintaining intracellular metal homeostasis, eliminating metal
      toxification and protecting against intracellular oxidative damages. Analysis of
      complete rice genome sequences revealed eleven genes encoding putative
      metallothionein (OsMT), indicating that OsMTs constitute a small gene family in
      rice. Expression profiling revealed that each member of the OsMT gene family
      differs not only in sequence but also in their tissue expression patterns,
      suggesting that these isoforms may have different functions they perform in
      specific tissues. On the basis of OsMT structural and phylogenetic analysis, the
      OsMT family was classified as two classes and class I was subdivided into four
      types. Additionally, in this paper we also present a complete overview of this
      family, describing the gene structure, genome localization, upstream regulatory
      element, and exon/intron organization of each member in order to provide valuable
      insight into this OsMT gene family.

PMID- 17002882
TI  - Molecular cloning and characterization of a novel calcium-dependent protein
      kinase gene IiCPK2 Responsive to polyploidy from tetraploid Isatis indigotica.
AB  - A novel calcium-dependent protein kinase gene (designated as IiCPK2) was cloned
      from tetraploid Isatis indigotica. The full-length cDNA of IiCPK2 was 2585 bp
      long with an open reading frame (ORF) of 1878 bp encoding a polypeptide of 625
      amino acid residues. The predicted IiCPK2 polypeptide included three domains: a
      kinase domain, a junction domain (or autoinhibitory region), and a C-terminal
      calmodulin-like domain (or calcium-binding domain), which presented a typical
      structure of plant CDPKs. Further analysis of IiCPK2 genomic DNA revealed that it
      contained 7 exons, 6 introns and the length of most exons was highly conserved.
      Semi-quantitative RTPCR revealed that the expression of IiCPK2 in root, stem and
      leaf were much higher in tetraploid sample than that in diploid progenitor.
      Further expression analysis revealed that gibberellin (GA3), NaCl and cold
      treatments could upregulate the IiCPK2 transcription. All our findings suggest
      that IiCPK2 might participate in the cold, high salinity and GA3 responsive
      pathways.

PMID- 17002883
TI  - The enhanced monocyte adhesiveness after UVB exposure requires ROS and NF-kappaB
      signaling in human keratinocyte.
AB  - The infiltration of both monocyte and activated T cells in the skin is one of
      critical steps in the development of UVB-induced inflammation. Upregulation of
      adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) on the
      surface of keratinocytes plays an important role in this process. In this study,
      we examined the molecular mechanism responsible for UVB-induced expression of
      ICAM-1 and subsequent monocyte adhesion by keratinocyte. We observed that (1) UVB
      induced protein and mRNA expression of ICAM-1 in a dose- and time-dependent
      manner in human keratinocyte cell HaCaT; (2) UVB induced the translocation of NF
      kappaB and inhibition of NF-kappaB by NF-kappaB inhibitors suppressed UVB-induced
      mRNA and protein expression of ICAM-1; (3) UVB increased the intracellular level
      of reactive oxygen species (ROS) by HaCaT cells; (4) UVB-induced increase of
      intracellular ROS level was suppressed by pretreatment with diphenyl iodonium
      (DPI) and N-acetyl cysteine (NAC); and (5) inhibition of UVB-induced ROS
      production by DPI or NAC suppressed UVB-mediated translocation of NF-kappaB,
      expression of ICAM-1 and subsequent monocyte adhesion in HaCaT cells. These
      results suggest that UVB-induced ROS is involved in the translocation of NF
      kappaB which is responsible for expression of ICAM-1 and subsequent increased
      monocyte adhesion in human keratinocyte.

PMID- 17002884
TI  - Identification of a novel human lysophosphatidic acid acyltransferase, LPAAT
      theta, which activates mTOR pathway.
AB  - Lysophosphatidic acid acyltransferase (LPAAT) is an intrinsic membrane protein
      that catalyzes the synthesis of phosphatidic acid (PA) from lysophosphatidic acid
      (LPA). It is well known that LPAAT is involved in lipid biosynthesis, while its
      role in tumour progression has been of emerging interest in the last few years.
      To date, seven members of the LPAAT gene family have been found in human. Here we
      report a novel LPAAT member, designated as LPAAT-theta, which was 2728 base pairs
      in length and contained an open reading frame (ORF) encoding 434 amino acids. The
      LPAAT-theta gene consisted of 12 exons and 11 introns, and mapped to chromosome
      4q21.23. LPAAT-theta was ubiquitously expressed in 18 human tissues by RT-PCR
      analysis. Subcellular localization of LPAAT-theta-EGFP fusion protein revealed
      that LPAAT-theta was distributed primarily in the endoplasmic reticulum (ER) of
      COS-7 cells. Furthermore, we found that the overexpression of LPAAT-theta can
      induce mTOR-dependent p70S6K phosphorylation on Thr389 and 4EBP1 phosphorylation
      on Ser65 in HEK293T cells.

PMID- 17002885
TI  - Interaction of native and apo-carbonic anhydrase with hydrophobic adsorbents: A
      comparative structure-function study.
AB  - Our previous studies indicated that native carbonic anhydrase does not interact
      with hydrophobic adsorbents and that it acquires this ability upon denaturation.
      In the present study, an apo form of the enzyme was prepared by removal of zinc
      and a comparative study was performed on some characteristic features of the apo
      and native forms by far- and near-UV circular dichroism (CD), intrinsic
      fluorescent spectroscopy, 1-anilino naphthalene-8-sulfonate (ANS) binding,
      fluorescence quenching by acrylamide, and Tm measurement. Results indicate that
      protein flexibility is enhanced and the hydrophobic sites become more exposed
      upon conversion to the apo form. Accordingly, the apo structure showed a greater
      affinity for interaction with hydrophobic adsorbents as compared with the native
      structure. As observed for the native enzyme, heat denaturation of the apo form
      promoted interaction with alkyl residues present on the adsorbents and, by
      cooling followed by addition of zinc, catalytically-active immobilized
      preparations were obtained.

PMID- 17002886
TI  - Expression, purification and transduction of PEP-1-botulinum neurotoxin type A
      (PEP-1-BoNT/A) into skin.
AB  - Botulinum neurotoxin A (BoNT/A) has been used therapeutically to treat muscular
      hypercontractions and sudomotor hyperactivity and it has been reported that
      BoNT/A might have analgesic properties in headache. PEP-1 peptide is a known
      carrier peptide that delivers full-length native proteins in vitro and in vivo.
      In this study, a BoNT/A gene were fused with PEP-1 peptide in a bacterial
      expression vector to produce a genetic in-frame PEP-1-BoNT/A fusion protein. The
      expressed and purified PEP-1-BoNT/A fusion proteins were efficiently transduced
      into cells in a time- and dose-dependent manner when added exogenously in a
      culture medium. In addition, immunohistochemical analysis revealed that PEP-1
      BoNT/A fusion protein efficiently penetrated into the epidermis as well as the
      dermis of the subcutaneous layer, when sprayed on mice skin. These results
      suggest that PEP-1-BoNT/A fusion protein provide an efficient strategy for
      therapeutic delivery in various human diseases related to this protein.

PMID- 17002887
TI  - A multiple chemical equilibria approach to modeling and interpreting the
      separation of amino acid enantiomers by chiral ligand-exchange chromatography.
AB  - A model of chiral ligand-exchange chromatography (CLEC) is presented that
      combines the non-ideal equilibrium-dispersion equation for solute transport with
      equations describing all chemical equilibria within the column. The model
      connects elution band profiles to the time and space resolved formation of
      diastereomeric complexes in both the mobile and stationary phases, thereby
      providing insights into the overall separation mechanism. The stoichiometries and
      formation constants for all equilibrium complexes formed in the mobile phase are
      taken from standard thermodynamic databases and independent potentiometric
      titration experiments. Formation constants for complexes formed with the
      stationary phase ligand are determined from potentiometric titration data for a
      water-soluble analogue of the ligand. Together this set of pure thermodynamic
      parameters can be used to calculate the equilibrium composition of the system at
      any operating condition. The model includes a temperature-dependent pure
      component parameter, determined by regression to a single elution band for the
      pure component, that corrects for subtle effects associated with immobilizing the
      ligand (i.e., the chiral selector) onto the stationary phase. Model performance
      is assessed through comparison with chromatograms for two hydrophobic amino acid
      racemates loaded on the Nucleosil Chiral-1 CLEC column. The model is also applied
      to a restricted optimization of column operating conditions to assess its
      predictive power. In both cases, model predictions compare well with experiment
      while also providing a molecular understanding of the separation process and its
      dependence on column operating conditions.

PMID- 17002888
TI  - Detection of protein carbonyls in aging liver tissue: A fluorescence-based
      proteomic approach.
AB  - Protein carbonyls are commonly used as a marker of protein oxidation in cells and
      tissues. Currently, 2,4-dinitrophenyl hydrazine (DNPH) is widely used
      (spectrophotometrically or immunologically) to quantify the global carbonyl
      levels in proteins and identify the specific proteins that are carbonylated. We
      have adapted a fluorescence-based approach using fluorescein-5-thiosemicarbazide
      (FTC), to quantify the global protein carbonyls as well as the carbonyl levels on
      individual proteins in the proteome. Protein carbonyls generated in vitro were
      quantified by labeling the oxidized proteins with FTC followed by separating the
      FTC-labeled protein from free probe by gel electrophoresis. The reaction of FTC
      with protein carbonyls was found to be specific for carbonyl groups. We measured
      protein carbonyl levels in the livers of young and old mice, and found a
      significant increase (two-fold) in the global protein carbonyl levels with age.
      Using 2-D gel electrophoresis, we used this assay to directly measure the changes
      in protein carbonyl levels in specific proteins. We identified 12 proteins
      showing a greater than two-fold increase in carbonyl content (pmoles of
      carbonyls/microg of protein) with age. Most of the 12 proteins contained
      transition metal binding sites, with Cu/Zn superoxide dismutase containing the
      highest molar ratio of carbonyls in old mice. Thus, the fluorescence-based assay
      gives investigators the ability to identify potential target proteins that become
      oxidized under different pathological and physiological conditions.

PMID- 17002889
TI  - Three-dimensional quantitative structure: activity relationship studies on
      diverse structural classes of HIV-1 integrase inhibitors using CoMFA and CoMSIA.
AB  - Comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA), three-dimensional quantitative structure-activity
      relationship (3D-QSAR) techniques, were applied to a set of 89 HIV-1 integrase
      (IN) inhibitors (training set=61, test set=28), belonging to 11 structurally
      different classes. The biological data for 3' processing mechanism were used. For
      CoMFA calculations, three different fitting methods for alignment process were
      investigated. The best CoMFA model yielded the cross-validated r(2) r(2)(cv)
      =0.698 and the non-cross-validated r(2) (r(2))=0.947. The derived model indicated
      the importance of steric (60.8%) as well as electrostatic (39.2%) contributions.
      For CoMSIA calculations, different combinations of the fields were tested. The
      best CoMSIA model gave r(2)(cv) =0.724 and r(2)=0.864. This model showed that
      steric (30.3%), hydrogen bond donor (43.4%) and hydrogen bond acceptor (26.3%)
      properties played major roles in HIV-1 IN inhibition. The mapping of hydrogen
      bond interaction fields with the HIV-1 IN active site gave details on hydrogen
      bond forming between ligands and enzyme. These obtained results agree well with
      the experimental observations that there should be hydrogen bond interactions
      between ligands and Glu152, Lys156 and Lys159 residues. The results not only lead
      to a better understanding of structural requirements of HIV-1 IN inhibitors but
      also can help in the design of new IN inhibitors.

PMID- 17002890
TI  - Parental adiposity and cortisol awakening responses in young men and women.
AB  - A heightened cortisol awakening response (CAR) is associated with adiposity in
      middle-aged men, but the causal significance of this effect is not known. We
      hypothesised that if disturbance in cortisol secretion is involved in the
      development of overweight and obesity, then it might be present in normal weight
      adults at increased risk of obesity on account of parental adiposity. The CAR and
      cortisol profile over the day were measured in 33 men and 62 women aged 18-25
      years. Parental adiposity was assessed with figure ratings derived from the
      Contour Drawing Rating Scale, and these were correlated with parental self
      reported body mass index (BMI) in a subset of participants (r=0.66-0.79). In men,
      a positive association was observed between the CAR and their judgements of their
      fathers' adiposity after controlling for age, smoking status, time of waking, and
      the participants' own BMI; the correlation was 0.56 (P=0.008) for the cortisol
      increase between waking and 30 min, and 0.47 (P=0.028) for the cortisol area
      under the curve. The correlation between the CAR and fathers' own reported BMI
      and figures ratings were also significant. The relationship between parental
      adiposity and the CAR in women was inconsistent, and the associations between the
      CAR and opposite gender parental adiposity were not significant. Parental
      adiposity was not related to cortisol output over the rest of the day or to the
      slope between waking and evening in either sex. The results of this study suggest
      that disturbances of cortisol secretion may present before the emergence of
      heightened adiposity in young men at raised risk for obesity.

PMID- 17002891
TI  - Elephant dung decomposition and coprophilous fungi in two habitats of semi-arid
      Botswana.
AB  - In order to understand the impact of habitat changes on ecosystem processes
      caused by increased populations of elephants, elephant dung decomposition was
      studied in semi-arid Botswana. Dung decomposition rates were studied with and
      without the presence of arthropods, using pairs of exposed dung and dung enclosed
      in nylon-mesh bags, respectively. Dung decomposition rates were lower in the
      absence of arthropods. The rates in the late wet season were higher in the
      scrubland than in the woodland. In the early dry season, immediately after the
      wet season, the rates were higher in the woodland than in the scrubland. The
      difference in decomposition rates between habitats was attributed to
      microclimatic conditions created by vegetation cover. With regard to fungal
      succession, Cladosporium cladosporioides and Eurotium brefeldianum occurred only
      in the late stages of dung decomposition whereas Talaromyces helicus, Cercophora
      coprophila and Sporormiella minima occurred in all the stages. Although there was
      no significant difference in Shannon-Weiner fungal species diversity index
      between habitats, seasons, dung ages and laboratory incubation periods, there
      were significant differences in fungal community composition between these
      parameters. Species richness was higher in the late wet season than in the early
      dry season, indicating the importance of moist conditions for a large diversity
      of fungal species.

PMID- 17002892
TI  - Relationship between airway colonization, inflammation and exacerbation frequency
      in COPD.
AB  - RATIONALE: To evaluate bacterial colonization and the airway inflammatory
      response, and its relationship to the frequency of exacerbation in patients with
      stable chronic obstructive pulmonary disease (COPD). METHODS: Quantitative
      bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor
      necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in
      bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent
      exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls
      (10 smokers and 8 non-smokers). RESULTS: BAL revealed the microorganisms with
      potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in
      68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40%
      of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF
      alpha levels were found to be significantly higher in COPD as compared to
      controls (P=0.001). However, only IL-8 level was significantly higher in COPD
      patients with frequent exacerbation as compared to infrequent (P=0.001). Airway
      bacterial load correlated with levels of airway inflammation markers in COPD
      (P<0.05). CONCLUSION: The bacterial load and airway inflammation contributes to
      each other in stable COPD. However, there is a link only between interleukine
      (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial
      colonization, airway inflammation and frequent exacerbations is of major
      importance in understanding of the COPD pathogenesis.

PMID- 17002893
TI  - Treatment of a full-thickness articular cartilage defect in the femoral condyle
      of an athlete with autologous bone-marrow stromal cells.
AB  - OBJECTIVES: Human bone-marrow stromal cells are believed to be multipotent even
      in adults. This study assessed the effectiveness of autologous bone-marrow
      stromal cells, which were embedded within a collagen scaffold, to repair a full
      thickness articular cartilage defect in the medial femoral condyle of an athlete.
      PATIENT AND METHODS: A 31-year-old male judo player suffering from pain in the
      right knee was reviewed. A 20 x 30-mm full-thickness cartilage defect
      (International Cartilage Repair Society classification (ICRS) grade IV) was
      revealed in the weight-bearing area of the medial femoral condyle. With the
      informed consent of the patient, the defect was treated with autologous bone
      marrow stromal cells. Bone marrow was aspirated from the iliac crest of the
      patient 4 weeks before surgery. After removing the erythrocytes, the remaining
      cells were expanded in culture. Adherent cells were collected and embedded within
      a collagen gel, which was transferred to the articular cartilage defect in the
      medial femoral condyle. The implant was covered with an autologous periosteal
      flap. RESULTS: Seven months after surgery, arthroscopy revealed the defect to be
      covered with smooth tissues. Histologically, the defect was filled with a hyaline
      like type of cartilage tissue which stained positively with Safranin-O. One year
      after surgery, the clinical symptoms had improved significantly. The patient had
      reattained his previous activity level and experienced neither pain nor other
      complications. CONCLUSIONS: Our findings indicate that the transplantation of
      autologous bone-marrow stromal cells can promote the repair of large focal
      articular cartilage defects in young, active patients.

PMID- 17002894
TI  - Microbial sensors for small molecules: development of a mevalonate biosensor.
AB  - We describe a novel biosensor strain for detection and quantification of a small
      molecule, mevalonate. The biosensor strain is an Escherichia coli mevalonate
      auxotroph that expresses the green fluorescent protein and reports on the
      mevalonate concentration in the growth medium through a change in growth rate. A
      model describing the growth rate dependence on mevalonate was developed in order
      to use the biosensor strain for high-throughput screening (HTS) and quantitative
      measurement of mevalonate in the extracellular environment. In general, this
      method should be applicable to the quantification of any small molecule for which
      an auxotroph can be developed and will be useful for HTS of evolved metabolic
      pathways for which there is no readily available screen or selection.

PMID- 17002895
TI  - Use of DNA arrays for the analysis of outbreak-related strains of Listeria
      monocytogenes.
AB  - We evaluated the discriminative power and usefulness of the DNA array technology
      as compared to DNA macrorestriction pattern analysis for monitoring
      epidemiologically related clusters of Listeria monocytogenes strains that differ
      slightly in DNA macrorestriction patterns. We show that this approach allows
      clarifying the genetic basis of the pattern variations. In the reported outbreak,
      the differences were due to phage excision, showing the power of this technique
      in epidemiological studies.

PMID- 17002896
TI  - Antigen-specific regulatory T-cell subsets in transplantation tolerance
      regulatory T-cell subset quality reduces the need for quantity.
AB  - Regulatory T cells (Treg) are critical controllers of the immune response.
      Disturbed Treg function results in autoimmunity, whereas in transplantation Treg
      are crucial in graft survival and transplant tolerance. Hence therapeutic
      modalities that influence Treg numbers or function hold great clinical
      opportunity. Ahead of us are clinical trails studying in vivo Treg induction
      protocols and immunotherapy with ex vivo expanded Treg. Here we discuss the
      preferential use and/or induction of antigen-specific Treg subsets with high
      suppressive power and migratory capacity as a potential therapeutic tool to
      prevent solid organ transplantation rejection. Accordingly, ex vivoselection
      procedures to induce and isolate highly suppressive antigen-specific Treg
      (subsets) are needed. This subject, as well as the Treg-facilitating potential of
      immunosuppressive agents, is discussed.

PMID- 17002897
TI  - Crosslinking of CD66B on peripheral blood neutrophils mediates the release of
      interleukin-8 from intracellular storage.
AB  - Crosslinking of CD66 antigens on the neutrophil surface induces functional
      responses such as aggregation of the cells and protein kinase activity. Although
      CD66b (carcinoembryonic antigen-related cell adhesion molecule-8) has been
      reported as a candidate receptor for galectin-3, its natural ligand is still
      unknown and therefore its physiologic function remains to be elucidated. We were
      able to detect the storage of intracellular interleukin-8 (IL-8) in unstimulated
      human neutrophils and its secretion in response to the crosslinking of CD66b. In
      contrast to lipopolysaccharide (LPS), the stimulation via CD66b does not induce a
      de novo synthesis of cytokines but rather a directed release of the preformed IL
      8. This process may represent a very low state of activation for the neutrophil.
      As it extravasates into the tissue, the neutrophil might interact with the
      extracellular matrix via CD66b. In response to this interaction,
      polymorphonuclear neutrophils (PMN) release their preformed IL-8, establishing a
      chemotactic track for other cells to follow. By contact with pathogenic stimuli
      such as LPS in the infected tissue, the neutrophil then becomes fully activated
      and is able to synthesize cytokines de novo to release greater quantities.

PMID- 17002898
TI  - Association of kidney transplant failure and antibodies against MICA.
AB  - Despite the progress in renal transplantation, acute rejection and graft failure
      still occur and chronic rejection continues to be the main problem in long-term
      allograft survival. Although kidney transplant rejection has been linked to anti
      HLA antibodies, not all patients with failed kidney transplants have anti-HLA
      antibodies, indicating that other loci may be involved. Sera of 63 patients who
      experienced kidney rejection were compared against sera of 82 patients with
      functioning transplants. Sera were examined for IgG and IgM anti-HLA Class I and
      II antibodies. They were also tested by cytotoxicity against panels of 26
      endothelial cell lines, 8 MHC class I chain-related gene A (MICA) recombinant
      cell lines, and 28 B lymphoblast cell lines. Among patients whose transplants
      failed, 65% had anti-HLA antibodies compared with 45% of those with functioning
      kidneys (p < 0.05). Similarly, among those whose transplants failed, 41% had anti
      endothelial cell antibodies in contrast to 22% in functioning patients (p <
      0.05). Among patients whose grafts failed, 52% had anti-MICA antibodies versus
      21% of those with functioning grafts (p < 0.001). Eleven patients with failed
      grafts and 32 with functioning grafts were negative for all of the above.
      However, 6 of the former and 7 of the latter showed positive cytotoxicity against
      B lymphoblasts (p < 0.05). Taking all antibodies together, 92% of patients with
      graft failure had antibodies as opposed to 70% of patients with functioning
      grafts (p < 0.001). We postulate that antibodies against HLA, MICA, endothelial
      cells, and B lymphoblasts could be independently involved in the slow process of
      chronic graft failure.

PMID- 17002899
TI  - Human monoclonal antibodies as a tool for the detection of HLA class I allele
      specific expression loss in head-and-neck squamous cell carcinoma and
      corresponding lymph node metastases.
AB  - Human leukocyte antigen (HLA) expression is important for the elimination of
      tumor cells by the immune system and immunotherapy. Activated T cells directed
      against tumor-associated antigens are fully capable of recognizing and
      eradicating neoplastic cells. Therefore, HLA expression loss is considered to be
      a main factor in tumor development. We report for the first time HLA-A and HLA-B
      allele-specific expression analysis by immunohistochemical staining of fresh
      tumor tissue and 9 lymph node metastases of 15 patients with head-and-neck
      squamous cell carcinoma. Heterogeneous HLA expression and HLA expression loss was
      detected in 13 tumor patients. Approximately 50% of the tumors had allele
      specific expression loss, which would have remained undetected using HLA
      monomorphic and locus-specific antibodies. In the majority of the patients with
      head-and-neck squamous cell carcinoma, HLA allele-specific expression loss
      differed between primary lesions and metastases. This is important for the
      efficacy of immunotherapy in these patients. It can be concluded that it is
      crucial to study HLA expression at the allele-specific level of primary lesions
      and metastases. It increases and refines our knowledge of HLA expression loss in
      tumorgenesis, which will improve the development of specific immunotherapy.

PMID- 17002900
TI  - Decreased risk for myocardial infarction and lower tumor necrosis factor-alpha
      levels in carriers of variants of the PDCD1 gene.
AB  - Increasing interest has been directed toward the inflammatory mechanisms involved
      in the pathogenesis of myocardial infarction (MI). In the search for genetic
      mechanisms underlying these inflammatory components, we studied variants of
      programmed cell death-1 (PDCD1), an immunoinhibitory receptor that inhibits
      lymphocyte activation and cytokine production, previously shown to be associated
      with several autoimmune disorders. The PD1.1, PD1.3, and PD1.6 polymorphisms of
      the PDCD1 gene were typed in the Stockholm Heart Epidemiology Program, a
      population-based clinical material consisting of 1179 first-time MI case patients
      and 1528 unaffected control subjects. Individual alleles and haplotypes were
      studied for association with levels of the inflammatory cytokines tumor necrosis
      factor-alpha (TNF-alpha), interleukin-6, and C-reactive protein and risk for MI.
      We observed a weak protective effect of PD1.3A allele for MI (odds ratio: 0.78,
      95% confidence interval: 0.61-0.98). We also observed decreased levels of TNF
      alpha in carriers of the PD1.1A/PD1.3G/PD1.6A haplotype, which is consistent with
      our previous observation that this haplotype may be protective from autoimmune
      conditions. Carriers of variants of the PDCD1 gene exhibit a decreased risk for
      nonfatal myocardial infarction, and PDCD1 mediates variation in TNF-alpha levels.

PMID- 17002901
TI  - NFkappaB and its inhibitor IkappaB in relation to type 2 diabetes and its
      microvascular and atherosclerotic complications.
AB  - Nuclear factor kappa B (NFkappaB) is an important transcription factor that
      together with its inhibitor (IkappaB) participates in the activation of genes
      involved in immune responses. We examined the CA repeat polymorphism of the NFKB1
      gene (encoding for NFkappaB) and A/G point variation in the 3'UTR region of the
      nuclear factor kappa B inhibitor alpha (NFKBIA) gene (encoding for IkappaB) in
      Czech and German patients with type 2 diabetes. The sample consisted of 211
      patients, both with and without kidney complications, and 159 controls.
      Additionally, 152 patients with systemic lupus erythematosus (SLE) were genotyped
      for NFKBIA polymorphism. We observed a significant increase in the homozygous AA
      genotype of the NFKBIA gene when compared with the control group (the highest
      value was in diabetics without diabetic nephropathy [p(c)* = 0.0015, odds ratio =
      3.59]). No differences were seen between the SLE and control groups. With regard
      to the polymorphism of the NFKB1 gene, we did not observe any significant
      differences between the groups. Since the AA genotype of the NFKBIA gene presents
      a risk for type 2 diabetes development but not for diabetic nephropathy alone, we
      believe that the NFkappaB gene polymorphism can influence the pathogenesis of
      diabetes mellitus and affect its complications. Negative findings relative to
      other inflammatory autoimmune diseases, such as SLE, suggest a specific
      relationship between NFkappaB and type 2 diabetes mellitus.

PMID- 17002902
TI  - Human leukocyte antigen non-class II determinants for type 1 diabetes in the
      Finnish population.
AB  - We explored the contribution of non-class II HLA loci to type 1 diabetes genetic
      susceptibility in the Finnish population. We analyzed 11 markers covering a 4-Mb
      region telomeric to the DQB1 gene in Finnish nuclear families with parents
      carrying either the DR8-DQB1*04 (n=188) or the DRB1*0404-DQB1*0302 haplotypes
      (n=135). On the DRB1*0404-DQB1*0302 haplotype we found independent disease
      association of the D6S273 and C125 markers (p(corr) = 10(-4) and 0.0095,
      respectively). The C125*200 alleles on this haplotype conferred an increased
      disease risk (OR = 3.6; p = 0.003). The B*39 allele also showed disease
      association (OR = 2.6; p = 0.054). The C125*200 allele appeared at an increased
      frequency also on transmitted B39 positive DRB1*0404-DQB1*0302 haplotypes,
      suggesting an independent effect. In addition, the C143*417 allele on the DRB1*08
      DQB1*04 haplotype was associated with decreased disease risk (OR = 0.48, p =
      0.003). Our data confirm that non-class II HLA loci affect genetic susceptibility
      to type 1 diabetes. In addition to HLA B*39 the C125 locus contributes to disease
      risk on the Finnish DRB1*0404-DQB1*0302 haplotypes. Another locus close to D6S273
      may also have an effect. For the first time we report that a locus near the C143
      marker appear to affect disease association of the DRB1*08-DQB1*04 haplotype.

PMID- 17002903
TI  - Diversity of the MBL2 gene in various Brazilian populations and the case of
      selection at the mannose-binding lectin locus.
AB  - The mannose binding lectin (MBL2) polymorphism is responsible for a common
      immunodeficiency in the human species. There were suggestions that the MBL2
      polymorphism has been under balancing selection, based on the high global
      frequency of alleles generating MBL deficiency and on the worldwide distribution
      of diseases negatively associated with them. To describe the distribution of MBL2
      allelic haplotypes in Brazilian populations and to discuss the evolution of this
      polymorphism, we analyzed six South Brazilian populations (152 Guarani
      Amerindian, 239 Kaingang Amerindian, 107 admixed, Brazilian 32 Afro-Brazilian,
      202 Euro-Brazilian and 16 Oriental-Brazilian). Eight haplotypes were observed:
      MBL2*HYPA, LYQA, LYPA, LXPA, LYPB, LYQC, HYPD, and LYPD. In addition, through
      sequencing of the promoter and exon 1 from Amerindian and Oriental individuals,
      three new single-nucleotide polymorphisms (SNPs) were found in the MBL2 promoter
      region in the Kaingang. Analysis of the sequencing data by neutrality tests
      (Tajima's D and Fu and Li's D* and F*) revealed no deviation from selective
      neutrality equilibrium in the Guarani and Kaingang. Significant Fay and Wu's H
      results are explained by the recent gene flow in these populations. Contrarily to
      previous thoughts, stochastic evolutionary factors seem therefore to have had a
      predominant role in shaping the MBL2 polymorphism, at least in the Amerindians.

PMID- 17002904
TI  - Interleukin (IL)-12, IL-2, and IL-6 gene polymorphisms in Takayasu's arteritis
      from Turkey.
AB  - Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology
      involving mainly the aorta and its major branches. Genetic polymorphisms of
      cytokines are screened as susceptibility factors for TA in Turkey. A total of 94
      patients with TA were investigated for the genetic polymorphisms of the
      interleukin genes IL12, IL2,and IL6 and were compared with 108 healthy control
      subjects using polymerase chain reaction-sequence-specific primer method. The
      frequencies of IL12B 1188 C allele (p = 0.03, OR = 1.7) and CC genotype (p =
      0.007, OR = 3.7) were both higher in TA patients than in control subjects. TT
      genotype at IL2-330 (p = 0.006, OR = 2.4) and GG genotype at IL6-174 (p = 0.04,
      OR = 1.9) were more frequent in TA patients. Lower prevalence of GT genotype at
      IL2-330 (p = 0.005, OR = 0.4), CG genotype at IL6-174 (p = 0.001, OR = 0.4), and
      AG genotypes at IL6-598 (p = 0.01, OR = 0.4) were also detected. The polymorphism
      of IL-12 as well as IL-6 and IL-2 genes may contribute to susceptibility and
      pathogenesis of TA by altering cytokine production and inducing inflammation.

PMID- 17002905
TI  - Interleukin-1 gene cluster polymorphism in chagas disease in a Colombian case
      control study.
AB  - The aim of this study was to assess the possible association between the IL1A,
      IL1B and IL1RN gene polymorphisms and Chagas disease. Our study population
      consisted of 130 serologically positive cardiomyopathic patients and 130
      seropositive and asymptomatic individuals from a Colombian population where
      Trypanosoma cruzi infection is endemic. Genotyping of the IL1A (-889C/T,
      +4845G/T), IL1B (-511C/T, -31T/C, +3954T/C, +5810G/A) and IL1RN (+8006T/C,
      +8061C/T, +11100T/C) polymorphisms was performed by polymerase chain reaction
      restriction fragment length polymorphism and polymerase chain reaction sequence
      specific primer methods. Statistically significant differences in the
      distribution of the IL1B +5810 genotypes were observed comparing cardiomyopathic
      patients and asymptomatic individuals (p = 0.036). Frequency of the GG genotype
      was higher in the cardiomyopathic patient group than in the asymptomatic group
      (13% versus 5%, p = 0.03, odds ratio [OR] = 2.64, 95% confidence interval [CI] =
      0.99-7.33). Differences in the distribution of the allele frequencies were also
      observed, being the +5810G allele overrepresented in patients with cardiomyopathy
      (37% versus 27%, p = 0.014, OR = 1.59, 95% CI = 1.08-2.36). Examination of
      markers in the IL1A (-889 and +4845), IL1B (-511, -31, and +3954) and IL1RN
      (+11100) genes revealed that the overall distribution of alleles and genotypes in
      patients with chagasic cardiomyopathy and asymptomatic were not significantly
      different. Our results show that in Colombian population the IL1B+5810G allele
      was associated with an increased risk chagasic cardiomyopathy. In addition, we
      demonstrated that homozygosity for the IL1B +5810G risk allele increased
      significantly the susceptibility to cardiomyopathy. This implies that the effect
      of IL1B gene on chagasic cardiomyopathy predisposition is dose dependent. We
      found that the haplotype CT of IL1B -31 and +3954 polymorphisms showed higher
      association with risk to chagasic cardiomyopathy (p(c) = 0.008, OR = 12.53) and
      the extended haplotype (CCTCATT) was significantly more frequent in asymptomatic
      than in cardiomyopathic patients (p = 0.0014, p(c) = 0.011, OR = 0.17). Therefore
      this study suggests that IL1 gene cluster polymorphisms may play a relevant role
      in the susceptibility to development of chagasic chronic cardiomyopathy.

PMID- 17002907
TI  - Sequence-based typing of the complete coding sequence of DQA1 and phenotype
      frequencies in the Dutch Caucasian population.
AB  - Typing of DQA1 by sequencing has been a challenge because of a 3-nucleotide
      deletion in exon 2 in half of the alleles. Furthermore, 19 of the 28 alleles
      cannot be identified on basis of exon 2 alone, but need additional exon
      information. With the sequencing strategy presented here the complete exons 1-4
      are sequenced heterozygously, enabling identification of all DQA1 alleles by
      sequence-based typing (SBT). Exons 1-4 were amplified and sequenced separately,
      the combined sequences were used for automated allele assignment. The method was
      validated by typing 21 individuals with all possible different allele group
      combinations. In addition 26 quality control samples were correctly typed by this
      method. To determine the phenotype frequencies 155 unrelated Dutch Caucasian
      individuals were DQA1 typed. In total 15 known and two new DQA1 alleles were
      identified. DQA1*0103 and *0505 were the most frequent alleles with phenotype
      frequencies of 30% and 29%, respectively. The SBT method presented here is an
      improvement compared to already existing protocols in that the complete exon
      sequence is obtained for all coding exons, using identical polymerase chain
      reaction conditions. Furthermore, all exons are sequenced heterozygously,
      facilitating allele assignment and reducing the number of amplification
      reactions.

PMID- 17002906
TI  - Association of HLA-DR and -DQ genes with narcolepsy in Koreans: comparison with
      two control groups, randomly selected subjects and DRB1*1501-DQB1*0602--positive
      subjects.
AB  - The purpose of this study was to investigate the association of human leukocyte
      antigen (HLA) class II alleles with narcolepsy-cataplexy susceptibility in
      Koreans. The distribution of HLA-DRB1 and -DQB1 alleles and presence or absence
      of DRB3/4/5 alleles were examined in 60 narcoleptic patients with clear-cut
      cataplexy, and the results were compared with two groups of healthy controls: 200
      randomly selected controls and 144 DRB1*1501-DQB1*0602 positive controls. All of
      the narcoleptic patients were DRB1*1501 and DQB1*0602 positive, and their
      frequencies were significantly higher in patients than in random controls (100%
      vs 17.0%, p(c) = 2.3 x 10(-30), OR = 583.96; 100% vs 16.5%, p(c) = 3.9 x 10(-31),
      OR = 605.00). The HLA association in Koreans was as tight as that reported in
      Japanese. Several DRB1 (*0101, *0405, *0901) and DQB1 alleles (*0303, *0401,
      *0501, *0601, *0604) were found to have weak protective effects against
      narcolepsy. DRB4 showed strong protective effect, and this was also significant
      when compared with DRB1*1501-DQB1*0602 positive controls (18.3% vs 44.4%, p(c) =
      0.001, OR = 0.28). DRB3 (OR = 1.86) and DQB1*0301 (OR = 2.45) were found to have
      weak predisposing effect, when compared with DRB1*1501-DQB1*0602 positive
      controls. The protective effect of DRB4 has to be further studied in other
      populations.

PMID- 17002908
TI  - Are current quality systems in nurse education fit for purpose: can we really be
      sure of current standards?

PMID- 17002909
TI  - The care and feeding of case managers.

PMID- 17002910
TI  - Alcohol in the older population part 1: grandma has a drinking problem?
AB  - Previously thought of as the elderly, the older population is most frequently
      defined as those age 60 and older; in short, "we older persons" are the baby
      boomers-although many of us do not want to consider ourselves older. We members
      of the boomer population, born between 1946 and 1964, generally consider
      ourselves vital, active, proactive, productive, and thriving. We often think the
      category "older"-those who are 65 years and older-is reserved for our parents, a
      misperception that misses a significant percentage of persons entering their
      older years. We do not stop to think that by 2010, baby boomers will increase the
      population of older adults to 40 million and begin to depend on Medicare. Twenty
      years later, in 2030, the 65-and-over population will hit 70 million; we "older
      persons" will be 1 out of every 5 Americans.

PMID- 17002911
TI  - Achieving breakthrough outcomes: measurable ROI.
AB  - You're a case manager. Your boss is talking return on investment (ROI). Your
      patients don't want to be numbers on a spreadsheet. What does it take to be a
      hero to both the boss and the patient? Case managers frequently try to argue that
      great gains in quality of life for the patient are so valuable that management
      ought to ease up on case managers when talking about budget and returns. An
      experienced quality professional might respond, "Good luck."

PMID- 17002912
TI  - Case management and quality: have we reached a tipping point?
AB  - In The Tipping Point, Malcolm Gladwell describes a phenomenon in which a niche
      market or fad undergoes transformation into mainstream acceptability, resulting
      in widespread social change. He concludes that a "tipping point" occurs when a
      series of small events results in a critical mass of acceptance that produces
      sudden major changes.

PMID- 17002913
TI  - Controlling workers' compensation costs for prescribed medication.
AB  - The rise in prescription drug costs in workers' compensation cases has become
      alarming. According to the National Council on Compensation Insurance (NCCI), the
      prescription drug share of total medical costs by accident year increased from
      6.5% in 1997 to 9.6% in 2001. Today, 10 cents of every dollar spent on medical
      care for workers' comp is spent on prescription drugs. Why the increase? The
      reasons vary; however, whatever the reason, it is critical to determine whether a
      prescribed drug is treating a work-related injury or another ailment unrelated to
      the injury. Knowing what questions to ask and where to go for additional
      information can help keep prescription medication costs under control.

PMID- 17002914
TI  - Applying life care planning principles in acute situations.
AB  - In autumn of 2004, a US stop-loss carrier requested consultation regarding their
      in-house catastrophic case-management program. Their market was self-funded
      Employee Retirement Income Security Act (ERISA) plans with fewer than 10,000
      lives. Although the company was committed to providing case management, they had
      problems with data gathering and communication with various third-party
      administrators (TPAs) for lack of a consistent flow of work and communication
      among all parties concerned. Their question: "Is case management provided by a
      stop-loss carrier viable in this circumstance?"

PMID- 17002915
TI  - Waiting and watching with Alzheimer's disease.

PMID- 17002917
TI  - Complement in asthma: sensitivity to activation and generation of C3a and C5a via
      the different complement pathways.
AB  - Studies in rodent models suggested that complement may play a critical role in
      susceptibility to airway hyperresponsiveness (AHR) and as a mediator of bronchial
      obstruction and inflammation in asthma. Complement may participate in
      susceptibility to asthma because of an intrinsic abnormality in complement
      activation and generation of C3a, C5a, or other products that affect cellular
      responses, resulting in T(H)2 predominance and asthma susceptibility.
      Alternatively, an intrinsic abnormality in the cellular response to complement
      activation products could determine susceptibility to asthma. In this study, the
      authors investigated whether complement in patients with atopic asthma versus
      nonatopic controls possesses an increased propensity to become activated. Despite
      reports that total complement plasma levels in unchallenged asthmatics are
      normal, an abnormal sensitivity of complement to activation may exist if an
      isoform or a polymorphic variant of a complement protein was present and resulted
      in gain or loss of function without associated changes in total complement
      levels. Therefore, complement activation was induced in vitro in plasma of
      asthmatics and controls using activators of the classical, alternative, and
      lectin pathways and measured C3a, other C3 fragments, and C5a. For each pathway,
      similar amounts of generated fragments, as well as C3a/C3 and C5a/C5 ratios, were
      found in asthmatics and controls. Also, similar basal plasma levels of C3a and
      C5a were found in both groups; however, mannan-binding lectin (MBL) levels were
      moderately elevated in asthmatics. In conclusion, the results suggest that, in
      asthmatic patients, complement activation does not exhibit an abnormal
      sensitivity to activation by any of the known activation pathways.

PMID- 17002918
TI  - Comparison of the effects of a new conjugated oral estrogen, estradiol-3beta
      glucoside, with oral micronized 17beta-estradiol in postmenopausal women.
AB  - The objective of this article is to evaluate the pharmacokinetics of serum
      estrone and estradiol levels in women who were taking either 17beta-estradiol
      3beta-glucoside (E(2)-3beta-glucoside) or 17beta-estradiol (E(2)) daily and to
      examine the effects of E(2)-3beta-glucoside and E(2) on postmenopausal symptoms,
      gonadotropins, hepatic metabolism, and coagulation factors. Healthy
      postmenopausal women on estrogen who had undergone a hysterectomy were recruited.
      Subjects were randomly assigned to receive equivalent doses of either E(2)-3beta
      glucoside or micronized E(2) for 28 days. Pharmacokinetic studies of estrone and
      estradiol were performed on days 1, 2, 28, and 29. Gonadotropin levels and
      Kupperman Index (KI) scores were determined at baseline and on treatment day 28.
      Mean serum estradiol and estrone concentrations in those taking E(2)-3beta
      glucoside were comparable with those taking E(2). Mean baseline follicle
      stimulating hormone (FSH) levels were 84 +/- 27 mIU/mL and 71 +/- 24 mIU/mL in
      the E(2)-3beta-glucoside and E(2) groups, respectively, with significant
      decreases (P < 0.01) of 54 +/- 21 mIU/mL and 38 +/-18 mIU/mL, respectively, by
      treatment day 28. Baseline KI scores in the E(2)-3beta-glucoside group were 10 +/
      6 compared with 5 +/- 4 on treatment day 28, which is equivalent to a 50%
      reduction in menopausal symptoms (P = 0.003). The change in KI scores in the E(2)
      group was not statistically significant. Total serum estradiol and estrone levels
      in women taking E(2)-3beta-glucoside are comparable with those in women taking
      E(2). E(2)-3beta-glucoside reduces serum gonadotropin levels to the premenopausal
      range and is effective at reducing postmenopausal symptoms. E(2)-3beta-glucoside
      is a novel synthetic estrogen that is well tolerated and has promise as a hormone
      replacement therapy.

PMID- 17002919
TI  - ERK contributes to the effects of Smad signaling on oxidized LDL-induced PAI-1
      expression in human mesangial cells.
AB  - Oxidized low-density lipoprotein (Ox-LDL) stimulates plasminogen activator
      inhibitor-1 (PAI-1) expression in human mesangial cells mediated by transforming
      growth factor-beta (TGF-beta)/Smad signaling pathway. TGF-beta activates
      extracellular signal-regulated kinase (ERK) in mesangial cells, and ERK is
      involved in activation of Smad2/3. This study examines whether an interaction
      exists between Ox-LDL-induced TGF-beta/Smad signaling pathways and ERK activation
      leading to PAI-1 transcription in human mesangial cells. Ox-LDL (50 microg/mL)
      induced an acute increase in ERK activity within 15 min, which decreased to
      control value at 2 h. Incubation with anti-TGF-beta or SB-431542, an inhibitor of
      the TGF-beta type I receptor, along with Ox-LDL, inhibited the expected increase
      in ERK phosphorylation. Treatment with PD98059 or UO126, mitogen-activated ERK
      activating kinase 1/2 inhibitors, significantly inhibited the Ox-LDL-induced
      increase in PAI-1 mRNA and nuclear Smad3 expression, DNA/protein complex
      formation, and PAI-1 promoter activity. These results suggest that
      phosphorylation of ERK is induced by Ox-LDL through the induction of the TGF-beta
      signaling pathway and that activated ERK, in turn, participates in the Ox-LDL
      induced Smad3 activation and subsequent PAI-1 gene expression in mesangial cells.

PMID- 17002920
TI  - Nitric oxide induces metallothionein-I gene expression in mesangial cells.
AB  - In various forms of injury involving the renal glomerulus, mesangial cells are
      exposed to potentially toxic concentrations of nitric oxide (NO) caused by
      activation of the inducible isoform of nitric oxide synthase (NOS). Whether
      mesangial cells possess systems that can defend against NO mediated oxidative
      injury is unknown. One putative system is Metallothionein (MT). Metallothioneins
      constitute a family of cysteine proteins and play a significant role as anti
      oxidants. The authors assessed whether NO upregulates MT-I expression in cultured
      glomerular mesangial cells. Northern blot analysis revealed that steady state MT
      I mRNA levels were increased by three different NO donors: sodium nitroprusside
      (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), and Spermine-NONOate
      (Sper/NO). The increase in MT-I mRNA levels induced by SNAP-derived NO was
      attenuated by the antioxidant N-acetylcysteine (NAC), a glutathione (GSH)
      precursor, which indicates that the mechanism of NO-mediated MT-I expression may
      involve an oxidative stress response. These observations identify MT-I as a
      putative antioxidant system in NO-mediated mesangial cell injury.

PMID- 17002921
TI  - Presence and severity of coronary artery disease and changes in B-type
      natriuretic peptide levels in patients with a normal systolic function.
AB  - B-type brain natriuretic peptide (BNP) levels increase during myocardial
      ischemia. Here, the authors undertook to evaluate the correlation between changes
      in plasma BNP levels during exercise and the presence and severity of coronary
      artery disease (CAD). The study subjects consisted of 159 hospitalized patients
      with a normal systolic function. Patients were allocated to a control group (N =
      101, comprising patients with coronary artery stenosis of < 50%) or to a CAD
      group (N = 58, comprising patients with stenosis of > or = 50% or a greater
      coronary artery lesion). In addition, the CAD group was further subdivided into a
      single-vessel disease (VD) subgroup (N = 31) and a multi-VD subgroup (N = 27).
      All 159 study subjects underwent coronary angiography (CAG), and plasma BNP
      levels were measured before and immediately after exercise. A comparative study
      of BNP levels in the control and CAD groups before and after exercise revealed
      that BNP levels in the CAD group were significantly higher [22.4 (5.0-28.5) vs.
      54.3 (13.1-74.6), P = 0.000; 35.0 (6.2-37.6) vs. 82.5 (23.2-102.8) pg/mL, P =
      0.002, respectively]. Changes in BNP levels during exercise in the CAD group
      tended to be greater than in the control group, but without significance [12.6 (0
      13.6) vs. 28.3 (2.8-25.5) pg/mL; P = 0.083]. Subgroup analysis showed that BNP
      levels tended to be positively related to the proportion of disease vessels, but
      statistical significance was only found between the control and multi-VD
      subgroup. Summarizing, this study shows that BNP level changes caused by exercise
      are closely related with the presence of CAD in patients with a normal systolic
      function. However, the relationship between these level changes and CAD severity
      requires further evaluation.

PMID- 17002922
TI  - Mixture models of serum iron measures in population screening for hemochromatosis
      and iron overload.
AB  - Homozygosity for the C282Y mutation of the hemochromatosis gene on chromosome 6p
      (HFE) is a common genetic trait that increases susceptibility to iron overload.
      The authors describe and apply methodology developed for the analysis of
      phenotypic and genotypic data from 46,136 non-Hispanic Caucasians, a subset of
      the multi-ethnic cohort enrolled in the Hemochromatosis and Iron Overload
      Screening (HEIRS) Study. For analysis of the distribution of transferrin
      saturation (TS), mixtures of normal distributions were considered and the
      expectation-maximization (EM) algorithm was applied for parameter estimation.
      Maximized log-likelihoods were compared, and significance was assessed by
      resampling. Sensitivity, specificity, and predictive values from the modeled
      subpopulations were compared with the actual observed genotypes for C282Y and
      H63D mutations in the HFE gene. A strong association between HFE genotype and TS
      subpopulations was found in these data collected from different geographic
      regions, confirming the external validity of the statistical approach when
      applied to population-based data. It was concluded that mixture modeling of
      phenotypic data may provide a clinical guide for screening with gender-specific
      thresholds to identify potential samples for genetic testing.

PMID- 17002923
TI  - Candin family antifungal agent micafungin (FK463) modulates the inflammatory
      cytokine production stimulated by lipopolysaccharide in THP-1 cells.
AB  - Systemic inflammatory response syndrome (SIRS) and sepsis have been considered
      forms of hypercytokinemia in critically ill patients and immunocompromized hosts.
      It has been reported that some antimicrobial agents, including antifungal agents,
      not only have an antibiotic effect, but also they affect the host's immunological
      response. Immunofunctional cells, including monocytes and macrophages, were
      examined to determine whether they are influenced by the newly synthesized candin
      family antifungal agent micafungin (MCFG) using the human monocytic cell line THP
      1 stimulated with lipopolysaccharide (LPS) as a model of hypercytokinetic
      conditions. LPS-induced production of TNF-alpha (tumor necrosis factor-alpha) and
      interleukin-8 (IL-8) in THP-1 cells was significantly suppressed dose-dependently
      by MCFG, although high concentrations of MCFG may reach toxic levels. It was
      clarified that MCFG inhibits the LPS-induced expression of TNF-alpha in THP-1
      cells at the mRNA (messenger ribonucleic acid) level. In conclusion,
      administration of MCFG had an immunomodulatory effect on the host by reducing
      levels of TNF-alpha and IL-8. The effectiveness of MCFG in modulating
      hypercytokinemia is due not only to its direct antifungal effect, but also to the
      modulation of cytokine production in macrophages that regulates immunological
      activity and inflammation.

PMID- 17002924
TI  - Inpatient management of hyperglycemia: the Northwestern experience.
AB  - OBJECTIVE: To describe a novel method of safe and effective intensive management
      of inpatient hyperglycemia with use of cost-effective protocols directed by a
      glucose management service (GMS). METHODS: An intravenous insulin protocol was
      designed to achieve a glycemic target of 80 to 110 mg/dL. When stable inpatients
      were transferred from the intravenous protocol to a subcutaneous insulin
      protocol, which consisted of basal long-acting and prandial and supplemental
      rapid-acting insulins, the blood glucose target was 80 to 150 mg/dL. Glucose
      levels were reviewed by the GMS at least daily for protocol adjustments, when
      necessary. RESULTS: The intravenous insulin protocol was used in 276 patients,
      and 4,058 capillary blood glucose levels were recorded. Glycemic target levels
      (80 to 110 mg/dL) were achieved, on average, 10.6 +/- 5.2 hours after initiation
      of insulin drip therapy. The mean capillary blood glucose level during the study
      interval was 135.3 +/- 49.9 mg/dL. Hypoglycemia (< or = 60 mg/dL) was recorded in
      1.5% of glucose values, and hyperglycemia (> or = 400 mg/dL) was recorded in only
      0.06%. The subcutaneous insulin protocol was used in 922 patients, and 18,067
      capillary glucose levels were documented. The mean blood glucose level was 145.6
      +/- 55.8 mg/dL during the study period. The blood glucose target of 80 to 150
      mg/dL was achieved in 58.6%, whereas 74.3% of glycemic values were in the
      clinically acceptable range (80 to 180 mg/dL). Hypoglycemia (< or = 60 mg/dL)
      occurred in 1.3% of capillary blood glucose values, and hyperglycemia (> or = 400
      mg/dL) occurred in 0.4% of values. CONCLUSION: Validated protocols dedicated to
      the achievement of strict glycemic goals were implemented by a GMS and resulted
      in substantial improvements in glycemic control on the surgical inpatient
      services, with a reduced frequency of hypoglycemia. The protocols and the GMS
      have been well received by the inpatient nursing and surgical staff members, and
      all of this has been done in a cost-effective manner.

PMID- 17002926
TI  - Medication persistence with weekly versus daily doses of orally administered
      bisphosphonates.
AB  - OBJECTIVE: To compare medication persistence among patients receiving daily
      orally administered bisphosphonates with persistence among patients receiving
      weekly orally administered bisphosphonates to ascertain whether less frequent
      dosing is associated with better long-term treatment persistence. METHODS: A
      large, longitudinal cohort of female patients (N = 211,319) receiving
      prescriptions for alendronate or risedronate from approximately 14,000 US retail
      pharmacies was assessed. Medication persistence was defined as the percentage of
      patients who continued to take bisphosphonate therapy during each month (that is,
      having at least 1 day of medication supply in that month) for a 1-year
      observation period. RESULTS: The inconvenience and complexity of required dosing
      procedures with oral bisphosphonate therapy for the prevention and treatment of
      osteoporosis are thought to be major factors that hinder medication persistence,
      and poor persistence is associated with suboptimal health-care outcomes. In this
      study, the percentage of patients continuing to take bisphosphonate therapy
      steadily declined with both daily and weekly oral treatment regimens during the
      course of the 12-month observation period. Consistently, however, medication
      persistence was higher among patients receiving the weekly rather than the daily
      regimen. Only 56.7% of patients receiving the weekly regimen and only 39.0% of
      patients receiving the daily regimen continued to take bisphosphonate therapy at
      month 12 of the study period (P<0.0001). CONCLUSION: This study demonstrates that
      weekly dosing of orally administered bisphosphonates is associated with higher
      medication persistence than is daily dosing. Nevertheless, more than 40% of
      patients did not persist with weekly bisphosphonate therapy for at least 12
      months. Thus, medication persistence was inadequate even with use of the weekly
      regimen. Additional research is needed to determine whether persistence can be
      further improved by extending the dosing interval beyond once weekly.

PMID- 17002925
TI  - Prevalence and treatment of anemia with once-weekly epoetin alfa in patients with
      diabetes and chronic kidney disease.
AB  - OBJECTIVE: To describe the characteristics and prevalence of anemia in patients
      with diabetes and chronic kidney disease (CKD) not receiving dialysis and to
      evaluate the efficacy and safety of once-weekly (QW) epoetin alfa for the
      treatment of anemia in these patients. METHODS: Post hoc subset analyses were
      conducted for 2 studies: a prospective, multicenter survey evaluating the
      prevalence of anemia in patients with CKD (the Prevalence of Anemia in Early
      Renal Insufficiency [PAERI] study) and a prospective, multicenter, open-label
      trial evaluating the efficacy and safety of QW epoetin alfa for the treatment of
      anemia associated with CKD (the Clinical Evaluation of Procrit Dosed Once Weekly
      in Patients With Anemia Due to Early Renal Insufficiency [POWER] study). Patients
      in the POWER study received epoetin alfa, 10,000 U subcutaneously QW for up to 16
      weeks. Each study subset consisted of patients with type 1 or type 2 diabetes.
      RESULTS: More than 60% of patients in both studies had diabetes. In the PAERI
      study, 52.4% of the patients with diabetes (N = 3,361) had a hemoglobin (Hb)
      level < or = 12 g/dL, and 10.5% had Hb < or = 10 g/dL. Female sex, African
      American race, reduced kidney function, reduced transferrin saturation, and
      diabetes as the cause of CKD were strongly associated with anemia. In the POWER
      study, the mean Hb level in the patients with diabetes (N = 816) increased from
      9.1 g/dL (baseline) to 11.6 g/dL (final); the mean increase in Hb from baseline
      was 2.4 g/dL (P<0.0001). Epoetin alfa therapy was associated with significant
      quality of life improvements and was well tolerated. CONCLUSION: Diabetes is
      prevalent in patients with CKD not receiving dialysis, and anemia is prevalent
      among these patients. Epoetin alfa QW is safe and effective in treating anemia in
      these patients.

PMID- 17002927
TI  - Effect of thyroid hormone replacement on methionine-stimulated homocysteine
      levels in patients with subclinical hypothyroidism: a randomized, double-blind,
      placebo-controlled study.
AB  - OBJECTIVE: To determine whether treatment of subclinical hypothyroidism with
      levothyroxine would improve homocysteine metabolism. METHODS: Twenty-four
      patients with subclinical hypothyroidism who had thyrotropin (thyroid-stimulating
      hormone or TSH) levels between 5 and 10 microIU/mL and normal free thyroxine
      concentrations were recruited from a primary care clinic and were randomized to
      receive levothyroxine (N = 12) or placebo (N = 12) for a period of 6 months in a
      double-blind, placebo-controlled study. Homocysteine was measured during fasting
      and after methionine challenge at the beginning and the end of the study in all
      patients treated with levothyroxine or placebo. RESULTS: The 12 patients treated
      with levothyroxine had normal TSH levels at the end of the study, with a median
      value of 1.8 microIU/mL. The 12 patients receiving placebo had a median TSH of
      6.0 microIU/mL after the 6-month study period. The ratio of fasting homocysteine
      at 6 months in comparison with baseline was 1.16 (95% confidence interval, 0.90
      to 1.63) for the levothyroxine-treated group and 1.00 (0.88 to 1.29) for the
      placebo group (P = 0.95). The ratio of post-methionine homocysteine at 6 months
      in comparison with baseline was 1.00 (95% confidence interval, 0.92 to 1.35) for
      the levothyroxine-treated group and 0.89 (0.68 to 1.05) for the placebo group (P
      = 0.081). CONCLUSION: In this study, levothyroxine treatment of patients with
      subclinical hypothyroidism did not alter homocysteine levels in the fasting or
      post-methionine states.

PMID- 17002928
TI  - Causes of hypercalcemia in a population of military veterans in the United
      States.
AB  - OBJECTIVE: To determine the various causes of hypercalcemia in a population of US
      veterans at the San Diego Veterans Affairs Medical Center. METHODS: A
      retrospective analysis of medical records was performed on 212 US veterans
      encountered between 1998 and 2002 with serum calcium measurements between 10.5
      and 10.9 mg/dL on multiple readings or 11.0 mg/dL (or greater) on any single
      determination. Data were collected from the clinical records for each patient and
      used to determine the cause of each patient's hypercalcemia. Patients undergoing
      hemodialysis were excluded from this study. RESULTS: The study population
      consisted of 201 men (95%) and 11 women (5%), with a median age of 63 years
      (range, 25 to 95). Of the 212 patients, 59 (28%) had a diagnosis of malignant
      disease, 38 (18%) had primary hyperparathyroidism, and 114 (54%) had
      hypercalcemia due to a range of other causes. The mean total serum calcium
      concentration for all patients in this study was 11.69 mg/dL. Lung carcinoma was
      the most prevalent malignant condition (in 17 patients or 29% of those with
      cancer). A single parathyroid adenoma (in 20 of 22 patients who underwent
      surgical intervention) accounted for the majority of cases of primary
      hyperparathyroidism. Among the other identified causes of hypercalcemia, acute
      renal failure was the most common (in 37 patients or 17% of all patients). In 37
      patients, no specific cause for the hypercalcemia was identified. CONCLUSION: To
      our knowledge, this is the first study to focus on hypercalcemia within the US
      veterans population. Although the 2 most common causes of hypercalcemia,
      hyperparathyroidism and malignant disease, were represented in this study, the
      majority of cases of hypercalcemia in this population of US veterans related to
      other etiologic factors.

PMID- 17002929
TI  - Glycemic control with continuous subcutaneous insulin infusion with use of U-500
      insulin in a pregnant patient.
AB  - OBJECTIVE: To demonstrate the benefits and to advocate the safety and efficacy of
      using an insulin pump with U-500 insulin in comparison with U-100 insulin for a
      pregnant patient with diabetes requiring massive doses of insulin. METHODS: We
      present a detailed case report about the use of continuous subcutaneous insulin
      infusion with U-500 insulin during pregnancy. Dose calculation is reviewed, and
      the benefits of insulin pump therapy in patients with diabetes are discussed.
      RESULTS: A 34-year-old white woman, with a history of type 2 diabetes for 7
      years, was seen at 17 weeks of gestation because of episodes of hyperglycemia and
      hypoglycemia accompanied by a very high insulin requirement. At the time of
      initial assessment, the patient was hospitalized with diabetic ketoacidosis and
      was being treated with 400 U/day of intravenously administered insulin. She
      responded well to intravenous therapy, but when switched to a regimen of NPH and
      regular insulin, she continued to have high blood glucose levels (despite 4 to 5
      insulin injections a day, with a total daily dose up to 400 to 450 U). Use of an
      insulin pump was instituted, which presented another challenge because of the
      limited reservoir capacity and the need to change sites at least once or twice a
      day. We decided to initiate U-500 insulin therapy with a total basal rate of 40
      U/day. Her meal carbohydrate insulin ratio and correction bolus were calculated
      on a U-100 scale. Then each estimated dose for meal coverage, depending on her
      carbohydrate intake, as well as the appropriate corrections were totaled and
      divided by 5 to convert to U-500. Throughout the rest of her pregnancy, the
      patient was able to maintain tight glycemic control, with no further
      hospitalizations for stabilization of hyperglycemia or hypoglycemia. CONCLUSION:
      To our knowledge, this is the first report of successful management of difficult
      to control diabetes by means of an insulin pump with use of U-500 insulin in a
      pregnant patient who required massive doses of insulin.

PMID- 17002930
TI  - Evolution of a pheochromocytoma.
AB  - OBJECTIVE: To present a case that demonstrates the evolution of a
      pheochromocytoma over a several-year period and to emphasize the importance of a
      thorough work-up for pheochromocytoma in patients with neurofibromatosis type 1
      (NF1) and hypertension. METHODS: We review the long-term clinical, biochemical,
      and imaging findings in a man with a complex medical history of hypertension,
      NF1, and cardiomyopathy. RESULTS: A 44-year-old man, with a well-documented
      history of headaches, hypertension, and NF1, was referred for evaluation of a
      right adrenal enlargement. He had developed cardiomyopathy and undergone an
      evaluation for cardiac transplantation. Initial computed tomography revealed
      subtle asymmetry in the upper right adrenal gland. Biochemical studies for
      pheochromocytoma yielded equivocal findings, with a 1.5-fold elevation in the
      urinary norepinephrine and near-normal urinary metanephrine level. Because 131I
      metaiodobenzylguanidine imaging showed no tracer uptake in the area of the right
      adrenal gland, the patient was thought not to have a pheochromocytoma. The
      patient eventually underwent cardiac transplantation and did well. On
      reassessment 3 1/2 years later, he was found to have a larger right adrenal mass.
      The second endocrine evaluation demonstrated substantial elevation in the urinary
      metanephrine level, and the patient underwent laparoscopic right adrenalectomy to
      remove the tumor (3.5 by 3.0 by 2.5 cm), which proved to be a pheochromocytoma.
      CONCLUSION: This case shows that a pheochromocytoma can be difficult to diagnose
      and can evolve to become a large, biochemically active tumor. It is imperative
      that patients with an adrenal tumor undergo periodic reevaluation to ensure that
      the tumor remains stable in size. If the tumor enlarges, further biochemical
      testing is warranted.

PMID- 17002931
TI  - Traumatic fracture in a healthy man: benign or pathologic?
AB  - OBJECTIVE: To describe the challenge of determining the correct diagnosis in a
      healthy adult male patient with a recent femoral fracture and a history of
      multiple bone fractures. METHODS: We present clinical, radiologic, laboratory,
      and histopathologic details in a patient with a history of recurrent fractures
      associated with minimal trauma. Moreover, the various types of osteopetrosis are
      reviewed. RESULTS: A 34-year-old African American man was in his usual state of
      good health when he fell hard on concrete. Immediately after the fall, he was
      able to bear weight, although pain prompted him to seek medical care. Besides a
      personal history of multiple fractures, he had no other medical problems. He had
      never smoked, denied illicit drug use, and had no family history of bone
      disorders or recurrent fractures. Findings on physical examination were
      unremarkable. Radiography disclosed an incomplete femoral fracture and
      osteosclerosis. Bone survey revealed diffuse, symmetric osteosclerosis of both
      the axial and the appendicular skeleton. The long bones showed areas of almost
      complete obliteration of the medullary canal, along with prominent hyperostosis.
      Additionally, a "bone-within-bone" appearance to the thickened endosteum was
      noted. A bone scan demonstrated numerous areas of symmetric radiotracer uptake.
      Laboratory analyses were unremarkable, including a complete blood cell count,
      electrolytes, serum protein electrophoresis, thyrotropin, and parathyroid
      hormone. Total alkaline phosphatase was mildly elevated at 162 U/L (normal range,
      35 to 130). Seven needles were broken during attempts to perform a bone biopsy.
      Histologic examination showed normal bone marrow with "woven" bone and areas of
      primary spongiosa within mature osteoid. Autosomal dominant osteopetrosis type 2
      was diagnosed on the basis of his clinical presentation and the radiologic and
      pathologic findings. CONCLUSION: The preliminary diagnosis for this patient's
      condition was Paget's disease, and determining the correct diagnosis of
      osteopetosis prevented the administration of inappropriate therapy. In addition,
      this case report reminds the clinician that genetic disease may manifest in
      adulthood.

PMID- 17002932
TI  - Renal tubular acidosis type 2 with Fanconi's syndrome, osteomalacia,
      osteoporosis, and secondary hyperaldosteronism in an adult consequent to vitamin
      D and calcium deficiency: effect of vitamin D and calcium citrate therapy.
AB  - OBJECTIVE: To describe a unique example of renal tubular acidosis type 2 (RTA 2)
      in conjunction with Fanconi's syndrome and osteomalacia consequent to vitamin D
      and calcium deficiency in an adult without underlying gastrointestinal disease.
      METHODS: We review the clinical, hormonal, histomorphometric, and micro-computed
      tomographic findings and the response to therapy with vitamin D and calcium in
      our patient. RESULTS: On admission, a 33-year-old African American woman had the
      following laboratory findings: serum ionized calcium 3.8 mg/dL (0.95 mmol/L),
      venous pH 7.26, bicarbonate 20 mEq/L, chloride 111 mEq/L, alkaline phosphatase
      1,192 U/L (20.26 microkat/L) (normal, 40 to 136 U/L), 25-hydroxyvitamin D <5
      ng/mL (<12 nmol/L) (normal, 10 to 60 ng/mL), parathyroid hormone 1,620 pg/mL
      (165.2 pmol/L) (normal, 10 to 60 pg/mL), aldosterone 68.4 ng/dL (1,894.7 pmol/L)
      (normal, 4.5 to 35.4 ng/dL), supine plasma renin activity 19.8 ng/mL per hour
      (5.35 ng/L per second) (normal, 0.5 to 1.8 ng/mL per hour), and aminoaciduria. A
      lumbar spine bone density T-score was -4.6, and a femoral neck T-score was -4.9.
      An undecalcified tetracycline-labeled bone biopsy specimen showed severe
      osteomalacia, severe osteoporosis, and peritrabecular fibrosis. A small
      intestinal biopsy revealed normal findings. Results of an ammonium chloride
      loading test and a bicarbonate infusion test were consistent with RTA 2. After 24
      months of vitamin D and calcium therapy, results of serum and urine chemistry
      studies and bicarbonate infusion normalized. The lumbar spine T-score improved to
      -2.0, and the femoral neck T-score improved to -2.7. Bone biopsy specimens
      demonstrated resolution of the osteomalacia. CONCLUSION: Nutritional vitamin D
      and calcium deficiency may cause RTA 2, Fanconi's syndrome, and osteomalacia in
      adults as well as in children.

PMID- 17002933
TI  - Utility of plasma free metanephrines in diagnosis of factitious pheochromocytoma.
AB  - OBJECTIVE: To report a case of epinephrine-induced factitious pheochromocytoma in
      a young woman with a past medical history of Conn's syndrome. METHODS: We present
      a case report with clinical and laboratory details, review related reports in the
      literature, and demonstrate the usefulness of plasma free metanephrine levels in
      facilitating the diagnosis of factitious pheochromocytoma. RESULTS: A 34-year-old
      woman was admitted to our hospital for confirmation and localization of an occult
      pheochromocytoma. After thorough investigation, we discovered that the patient
      was surreptitiously injecting epinephrine in order to induce symptoms and signs
      consistent with a pheochromocytoma. Analysis of the patient's biochemical profile
      during and between her catecholaminergic crises revealed plasma epinephrine and
      free metanephrine levels that would be highly unusual for a patient with a
      pheochromocytoma. CONCLUSION: This case illustrates the utility of implementing
      the ratio of plasma epinephrine to free metanephrine levels in distinguishing
      factitious from organic pheochromocytoma.

PMID- 17002934
TI  - Reversible subclinical hypothyroidism in the presence of adrenal insufficiency.
AB  - OBJECTIVE: To describe 3 different scenarios of reversible hypothyroidism in
      young patients with adrenal insufficiency. METHODS: We present 3 case reports of
      patients with adrenal insufficiency--one with delayed puberty, the second with
      type 1 diabetes and poor weight gain, and the third with hypoglycemia-related
      seizures and glucocorticoid deficiency--who had biochemical evidence of
      hypothyroidism. RESULTS: Our first patient (case 1) initially had a mildly
      elevated thyrotropin (thyroid-stimulating hormone or TSH) level and a normal free
      thyroxine (FT4) level that, on follow-up assessment, had progressed to persistent
      mild elevation of TSH and low FT4 concentration. The other 2 patients (cases 2
      and 3) had low FT4 and mildly elevated TSH values at the time of diagnosis of
      adrenal insufficiency. In all 3 patients, the results of thyroid function tests
      normalized with use of physiologic doses of adrenal hormone replacement therapy,
      without thyroid hormone replacement. All 3 patients remained euthyroid after 4,
      3, and 1 year of follow-up, respectively. CONCLUSION: These observations add
      insights into the complexities of the thyroadrenal interactions. These examples
      are important because thyroid hormone replacement in the setting of adrenal
      insufficiency could be unwarranted.

PMID- 17002935
TI  - Vitamin E in humans: an explanation of clinical trial failure.
AB  - OBJECTIVE: To describe the potential benefits and hazards of vitamin E
      supplementation and present a rational basis for understanding the conflicting
      results among randomized clinical trials, epidemiologic investigations, and
      animal studies on the use of vitamin E to prevent atherosclerosis. METHODS: We
      conducted a retrospective review of the pertinent literature found in PubMed from
      1981 through August 2005. The published data are analyzed and summarized.
      RESULTS: The possible factors implicated for failure of vitamin E therapy include
      the following: (1) the inclusion of patients without biochemical evidence of
      increased oxidative stress, (2) the relatively short duration of treatment, (3)
      the use of suboptimal dosages of vitamin E, (4) the suppression of gamma
      tocopherol by alpha-tocopherol, (5) the use of vitamin E supplementation without
      the concurrent use of vitamin C, (6) the lack of inclusion of biochemical markers
      of oxidative stress and markers of vascular response, (7) the inappropriate
      administration of vitamins relative to meal ingestion, and (8) the poor patient
      compliance and the lack of monitoring of vitamin E levels. CONCLUSION: Large,
      randomized clinical trials have not yet substantiated a beneficial effect of use
      of vitamin E to reduce atherosclerotic risk in humans, despite demonstration of
      antioxidant effects in vitro and in animals. Only in subsets of patients at high
      risk for atherosclerosis has a beneficial effect been suggested. Before
      additional large, randomized clinical trials of vitamin E are performed, the
      specific biologic and surrogate marker effects of vitamin E in each target
      population must be defined more carefully. This approach will save resources,
      minimize untoward side effects, and identify the patients who will benefit the
      most.

PMID- 17002936
TI  - Diabetic foot disease.
AB  - OBJECTIVE: To review the spectrum of foot problems in patients with diabetes and
      the underlying etiologic factors. METHODS: In this review, the term "diabetic
      foot disease" (DFD) will be used (previously referred to as simply "diabetic
      foot"). The relevant anatomy of the foot is discussed, the clinical evaluation
      and severity of DFD are outlined, and the role of both systemic control and local
      measures in the management of DFD is addressed. RESULTS: DFD is linked with a
      wide variety of etiologic associations, pathologic forms, and clinical severity.
      The causes of DFD include such factors as diabetic neuropathy, vascular
      insufficiency, and the presence of underlying bone deformity. The pathologic
      forms range from superficial skin lesions, soft tissue infections, joint
      swellings, and deformities to frank necrosis and gangrene. The clinical severity
      ranges from mild, self-resolving disease to fulminant, rapidly progressive
      disease that usually eventuates in amputation. The heterogeneity of patients
      whose illness is grouped collectively under the diagnosis of DFD has contributed
      to the persisting confusion and controversy regarding the optimal classification
      system for diabetes-related foot problems and their appropriate management.
      CONCLUSION: Optimal management of DFD involves a multimodality approach directed
      at regular foot care, blood glucose control, and early recognition of foot
      problems. Appropriate surgical management, administration of systemic
      antibiotics, and off-loading techniques are necessary to prevent the progression
      of DFD.

PMID- 17002937
TI  - Diagnosis of mosaic Turner's syndrome in a middle-aged woman.

PMID- 17002938
TI  - Idle thoughts from an addled mind. Not worth mentioning.

PMID- 17002939
TI  - Inpatient diabetes control on general medical and surgical units: where's the
      (good) data?

PMID- 17002940
TI  - Visual vignette. Jejunojejunal (small bowel) intestinal intussusceptions.

PMID- 17002941
TI  - Visual vignette. What is the location of the "jumping thyroid nodule"?

PMID- 17002942
TI  - Herbivory: effects on plant abundance, distribution and population growth.
AB  - Plants are attacked by many different consumers. A critical question is how
      often, and under what conditions, common reductions in growth, fecundity or even
      survival that occur due to herbivory translate to meaningful impacts on
      abundance, distribution or dynamics of plant populations. Here, we review
      population-level studies of the effects of consumers on plant dynamics and
      evaluate: (i) whether particular consumers have predictably more or less
      influence on plant abundance, (ii) whether particular plant life-history types
      are predictably more vulnerable to herbivory at the population level, (iii)
      whether the strength of plant-consumer interactions shifts predictably across
      environmental gradients and (iv) the role of consumers in influencing plant
      distributional limits. Existing studies demonstrate numerous examples of
      consumers limiting local plant abundance and distribution. We found larger
      effects of consumers on grassland than woodland forbs, stronger effects of
      herbivory in areas with high versus low disturbance, but no systematic or
      unambiguous differences in the impact of consumers based on plant life-history or
      herbivore feeding mode. However, our ability to evaluate these and other patterns
      is limited by the small (but growing) number of studies in this area. As an
      impetus for further study, we review strengths and challenges of population-level
      studies, such as interpreting net impacts of consumers in the presence of density
      dependence and seed bank dynamics.

PMID- 17002943
TI  - Evidence that female preferences have shaped male signal evolution in a clade of
      specialized plant-feeding insects.
AB  - Mate choice is considered an important influence in the evolution of mating
      signals and other sexual traits, and--since divergence in sexual traits causes
      reproductive isolation--it can be an agent of population divergence. The
      importance of mate choice in signal evolution can be evaluated by comparing male
      signal traits with female preference functions, taking into account the shape and
      strength of preferences. Specifically, when preferences are closed (favouring
      intermediate values), there should be a correlation between the preferred values
      and the trait means, and stronger preferences should be associated with greater
      preference-signal correspondence and lower signal variability. When preferences
      are open (favouring extreme values), signal traits are not only expected to be
      more variable, but should also be shifted towards the preferred values. We tested
      the role of female preferences in signal evolution in the Enchenopa binotata
      species complex of treehoppers, a clade of plant-feeding insects hypothesized to
      have speciated in sympatry. We found the expected relationship between signals
      and preferences, implicating mate choice as an agent of signal evolution. Because
      differences in sexual communication systems lead to reproductive isolation, the
      factors that promote divergence in female preferences--and, consequently, in male
      signals--may have an important role in the process of speciation.

PMID- 17002944
TI  - Acetylcholinesterase genes within the Diptera: takeover and loss in true flies.
AB  - It has recently been reported that the synaptic acetylcholinesterase (AChE) in
      mosquitoes is encoded by the ace-1 gene, distinct and divergent from the ace-2
      gene, which performs this function in Drosophila. This is an unprecedented
      situation within the Diptera order because both ace genes derive from an old
      duplication and are present in most insects and arthropods. Nevertheless,
      Drosophila possesses only the ace-2 gene. Thus, a secondary loss occurred during
      the evolution of Diptera, implying a vital function switch from one gene (ace-1)
      to the other (ace-2). We sampled 78 species, representing 50 families (27% of the
      Dipteran families) spread over all major subdivisions of the Diptera, and looked
      for ace-1 and ace-2 by systematic PCR screening to determine which taxonomic
      groups within the Diptera have this gene change. We show that this loss probably
      extends to all true flies (or Cyclorrhapha), a large monophyletic group of the
      Diptera. We also show that ace-2 plays a non-detectable role in the synaptic AChE
      in a lower Diptera species, suggesting that it has non-synaptic functions. A
      relative molecular evolution rate test showed that the intensity of purifying
      selection on ace-2 sequences is constant across the Diptera, irrespective of the
      presence or absence of ace-1, confirming the evolutionary importance of non
      synaptic functions for this gene. We discuss the evolutionary scenarios for the
      takeover of ace-2 and the loss of ace-1, taking into account our limited
      knowledge of non-synaptic functions of ace genes and some specific adaptations of
      true flies.

PMID- 17002945
TI  - Developmental response to cold stress in cranial morphology of Rattus:
      implications for the interpretation of climatic adaptation in fossil hominins.
AB  - Adaptation to climate occupies a central position in biological anthropology. The
      demonstrable relationship between temperature and morphology in extant primates
      (including humans) forms the basis of the interpretation of the Pleistocene
      hominin Homo neanderthalensis as a cold-adapted species. There are contradictory
      signals, however, in the pattern of primate craniofacial changes associated with
      climatic conditions. To determine the direction and extent of craniofacial change
      associated with temperature, and to understand the proximate mechanisms
      underlying cold adaptations in vertebrates in general, dry crania from previous
      experiments on cold- and warm-reared rats were investigated using computed
      tomography scanning and three-dimensional digitization of cranial landmarks.
      Aspects of internal and external cranial morphology were compared using standard
      statistical and geometric morphometric techniques. The results suggest that the
      developmental response to cold stress produces subtle but significant changes in
      facial shape, and a relative decrease in the volume of the maxillary sinuses (and
      nasal cavity), both of which are independent of the size of the skull or
      postcranium. These changes are consistent with comparative studies of temperate
      climate primates, but contradict previous interpretations of cranial morphology
      of Pleistocene Hominini.

PMID- 17002946
TI  - Rapid adaptive divergence of life-history traits in response to abiotic stress
      within a natural population of a parthenogenetic nematode.
AB  - Sexual reproduction is acknowledged to facilitate adaptation to novel
      environments while asexual eukaryotes are often regarded as having low adaptive
      potential. This view has been challenged in a number of studies, but the adaptive
      potential of asexual populations in the field is poorly documented. We
      investigated the response of natural populations of the parthenogenetic nematode
      Acrobeloides nanus to imposed divergent selective pressures. For this purpose, we
      employed a replicated evolution experiment in the field. After 20 years of
      evolution under abiotic stress and control conditions, life-history traits were
      assessed in reaction norm- and reciprocal transplant experiments. Both these
      experiments indicated adaptive divergence within the population of A. nanus.
      Namely, the transplant experiment demonstrated that in the stressed soil
      environment, body growth rate was more reduced in the nematodes originating from
      the control treatment. In the reaction norm experiment, survival and reproduction
      were higher under test conditions corresponding to the native environment of the
      nematodes. The differences in the analysed traits are discussed in the context of
      life-history theory. Overall, our results strongly support high adaptive
      potential of A. nanus and suggest that population structure and distribution of
      asexual species is shaped by local adaptation events.

PMID- 17002947
TI  - Vitamin D supplementation increases the attractiveness of males' scent for female
      Iberian rock lizards.
AB  - Evolutionary theory proposes that signals used in sexual selection can only be
      stable if they are honest and condition dependent. However, despite the fact that
      chemical signals are used by many animals, empirical research has mainly focused
      on visual and acoustic signals. Vitamin D is an essential nutrient for lizards,
      but in some lizards its precursor (cholesta-5,7-dien-3-ol=provitamin D) is found
      in femoral gland secretions, which males use for scent marking and intraspecific
      communication. By allocating provitamin D to secretions, males might need to
      divert vitamin D from metabolism. This might be costly and condition dependent.
      We tested whether diet quality affected chemical signals of male Iberian rock
      lizards (Lacerta monticola) and its consequences for sexual selection. After
      experimental supplementation of dietary vitamin D, males increased the proportion
      of provitamin D in femoral secretions. Further experiments showed that females
      detected these changes in males' signals by chemosensory cues, and discriminated
      provitamin D, and changes in its concentration, from similar steroids (i.e.
      cholesterol) found in secretions. Moreover, females preferred areas scent marked
      by males with more provitamin D in their secretions. This mechanism would confer
      honesty to chemical signals of male lizards, and, thus, females may rely on it to
      select high-quality males. We suggest that the allocation of vitamins and other
      essential nutrients to either visual (e.g. carotenoids) or chemical ornaments
      might be the common basis of honest sexual displays in many animals.

PMID- 17002948
TI  - Deep-sea food bonanzas: early Cenozoic whale-fall communities resemble wood-fall
      rather than seep communities.
AB  - The evolutionary history of invertebrate communities utilizing whale carcasses
      and sunken wood in the deep-sea is explored using fossil evidence. Compared to
      modern whale-fall communities, the Eo-Oligocene examples lack those vent-type
      taxa that most heavily rely on sulphide produced by anaerobic breakdown of bone
      lipids, but are very similar in their trophic structure to contemporaneous wood
      falls. This sheds doubt on the hypothesis that whale-falls were evolutionary
      stepping stones for taxa that now inhabit hydrothermal vents and seeps. We
      suggest that the whale-fall communities reported here represent a new ecologic
      stage among whale-falls, which we have coined the 'chemosymbiotic opportunist
      stage' and that the 'sulphophilic stage' of modern whale-falls developed during
      the Early Miocene, resulting from a significant increase in both body size and/or
      oil content of bones among cetaceans during this time.

PMID- 17002949
TI  - Inbreeding and disease resistance in a social insect: effects of heterozygosity
      on immunocompetence in the termite Zootermopsis angusticollis.
AB  - Recent research has shown that low genetic variation in individuals can increase
      susceptibility to infection and group living may exacerbate pathogen
      transmission. In the eusocial diploid termites, cycles of outbreeding and
      inbreeding characterizing basal species can reduce genetic variation within
      nestmates during the life of a colony, but the relationship of genetic
      heterogeneity to disease resistance is poorly understood. Here we show that, one
      generation of inbreeding differentially affects the survivorship of isolated and
      grouped termites (Zootermopsis angusticollis) depending on the nature of immune
      challenge and treatment. Inbred and outbred isolated and grouped termites
      inoculated with a bacterial pathogen, exposed to a low dose of fungal pathogen or
      challenged with an implanted nylon monofilament had similar levels of immune
      defence. However, inbred grouped termites exposed to a relatively high
      concentration of fungal conidia had significantly greater mortality than outbred
      grouped termites. Inbred termites also had significantly higher cuticular
      microbial loads, presumably due to less effective grooming by nestmates. Genetic
      analyses showed that inbreeding significantly reduced heterozygosity and allelic
      diversity. Decreased heterozygosity thus appeared to increase disease
      susceptibility by affecting social behaviour or some other group-level process
      influencing infection control rather than affecting individual immune physiology.

PMID- 17002950
TI  - The relationship between migratory behaviour, memory and the hippocampus: an
      intraspecific comparison.
AB  - It has been hypothesized that memory-demanding ecological conditions might result
      in enhanced memory and an enlarged hippocampus, an area of the brain involved in
      memory processing, either via extensive memory experience or through evolutionary
      changes. Avian migration appears to represent one of such memory-demanding
      ecological conditions. We compared two subspecies of the white-crowned sparrow:
      migratory Zonotrichia leucophrys gambelii and non-migratory Z. l. nuttalli.
      Compared to non-migratory Z. l. nuttalli, migratory Z. l. gambelii showed better
      memory performance on spatial one-trial associative learning tasks and had more
      hippocampal neurons. Migratory subspecies also had larger hippocampi relative to
      the remainder of the telencephalon but not relative to body mass. In adults, the
      differences between migratory and non-migratory sparrows were especially
      pronounced in the right hippocampus. Juvenile migratory Z. l. gambelii had
      relatively larger hippocampal volume compared to juvenile non-migratory Z. l.
      nuttalli. Adult migratory Z. l. gambelii had more neurons in their right
      hippocampus compared to juveniles but such differences were not found in non
      migratory Z. l. nuttalli. Our results suggest that migratory behaviour might be
      related to enhanced spatial memory and an enlarged hippocampus with more neurons,
      and that differences in the hippocampus between migratory and non-migratory
      sparrows might be experience-dependent. Furthermore, for the first time our
      results suggest that the right hippocampus, which encodes global spatial
      information, might be involved in migratory behaviour.

PMID- 17002951
TI  - Evidence for an apartheid-like social structure in early Anglo-Saxon England.
AB  - The role of migration in the Anglo-Saxon transition in England remains
      controversial. Archaeological and historical evidence is inconclusive, but
      current estimates of the contribution of migrants to the English population range
      from less than 10000 to as many as 200000. In contrast, recent studies based on Y
      chromosome variation posit a considerably higher contribution to the modern
      English gene pool (50-100%). Historical evidence suggests that following the
      Anglo-Saxon transition, people of indigenous ethnicity were at an economic and
      legal disadvantage compared to those having Anglo-Saxon ethnicity. It is likely
      that such a disadvantage would lead to differential reproductive success. We
      examine the effect of differential reproductive success, coupled with limited
      intermarriage between distinct ethnic groups, on the spread of genetic variants.
      Computer simulations indicate that a social structure limiting intermarriage
      between indigenous Britons and an initially small Anglo-Saxon immigrant
      population provide a plausible explanation of the high degree of Continental male
      line ancestry in England.

PMID- 17002952
TI  - Biotic homogenization and changes in species diversity across human-modified
      ecosystems.
AB  - Changing land use and the spread of 'winning' native or exotic plants are
      expected to lead to biotic homogenization (BH), in which previously distinct
      plant communities become progressively more similar. In parallel, many ecosystems
      have recently seen increases in local species (alpha-) diversity, yet gamma
      diversity has continued to decline at larger scales. Using national ecological
      surveillance data for Great Britain, we quantify relationships between change in
      alpha-diversity and between-habitat homogenizations at two levels of
      organization: species composition and plant functional traits. Across Britain
      both increases and decreases in alpha-diversity were observed in small random
      sampling plots (10-200m2) located within a national random sample of 1km square
      regions. As alpha-diversity declined (spatially in 1978 or temporally between
      1978 and 1998), plant communities became functionally more similar, but species
      compositional similarity declined. Thus, different communities converged on a
      narrower range of winning trait syndromes, but species identities remained
      historically contingent, differentiating a mosaic of residual species-poor
      habitat patches within each 1km square. The reverse trends in beta-diversity
      occurred where alpha-diversity increased. When impacted by the same type and
      intensity of environmental change, directions of change in alpha-diversity are
      likely to depend upon differences in starting productivity and disturbance. This
      is one reason why local diversity change and BH across habitats are not likely to
      be consistently coupled.

PMID- 17002953
TI  - Are algal communities driven toward maximum biomass?
AB  - In this continental-scale study, we show that in major benthic and planktonic
      stream habitats, algal biovolume--a proxy measure of biomass--is a unimodal
      function of species richness (SR). The biovolume peak is observed at intermediate
      to high SR in the benthos but at low richness in the phytoplankton. The unimodal
      nature of the biomass-diversity relationship implies that a decline in algal
      biomass with potential harmful effects on all higher trophic levels, from
      invertebrates to fish, can result from either excessive species gain or species
      loss, both being common consequences of human-induced habitat alterations. SR
      frequency distributions indicate that the most frequent richness is habitat
      specific and significantly higher in the benthos than in the plankton. In all
      studied stream environments, the most frequent SR is lower than the SR that
      yields the highest biovolume, probably as a result of anthropogenic influences,
      but always within one standard deviation from it, i.e. they are statistically
      indistinguishable. This suggests that algal communities may be driven toward
      maximum biomass.

PMID- 17002954
TI  - Rates of nausea and vomiting in pregnancy and dietary characteristics across
      populations.
AB  - Nausea and vomiting in pregnancy (NVP) is a pervasive and debilitating phenomenon
      in humans. Several adaptive explanations for NVP occurrence have been recently
      proposed, the two most prominent of which predict associations with nutritional
      intake or specific dietary components. Here we extend previous cross-cultural
      analyses by analysing associations between NVP prevalence in 56 studies (21
      countries) and quantitative estimates of per capita intake across major dietary
      categories, measured for the year of study by the Food and Agriculture
      Organisation (FAO). Rates of nausea and vomiting in pregnancy were correlated
      with high intake of macronutrients (kilocalories, protein, fat, carbohydrate), as
      well as sugars, stimulants, meat, milk and eggs, and with low intake of cereals
      and pulses. Restricting analyses to studies from North America and Europe caused
      relationships between macronutrient intake and NVP to disappear, suggesting that
      they might be influenced by non-dietary confounds associated with geographical
      region of study. However, factor analysis of dietary components revealed one
      factor significantly associated with NVP rate, which was characterized by low
      cereal consumption and high intake of sugars, oilcrops, alcohol and meat. The
      results provide further evidence for an association between diet and NVP
      prevalence across populations, and support for the idea that NVP serves an
      adaptive prophylactic function against potentially harmful foodstuffs.

PMID- 17002955
TI  - Stochastic re-calibration: contextual effects on perceived tilt.
AB  - The human visual system exaggerates the difference between the tilts of adjacent
      lines or grating patches. In addition to this tilt illusion, we found that
      oblique flanks reduced acuity for small changes of tilt in the centre of the
      visual field. However, no flanks--regardless of their tilts--decreased
      sensitivity to contrast. Thus, the foveal tilt illusion should not be attributed
      to orientation-selective lateral inhibition. Nor is it similar to conventional
      crowding, which typically does not impair letter recognition in the fovea. Our
      observers behaved as though the reference orientation (horizontal) had a small
      tilt in the direction of the flanks. We suggest that the extent of this re
      calibration varies randomly over trials, and we demonstrate that this stochastic
      re-calibration can explain flank-induced acuity loss in the fovea.

PMID- 17002956
TI  - "A catalogue of biases": the need for a European perspective on antidepressants'
      evidence in general practice.

PMID- 17002957
TI  - Regulatory end-point assessment of the consultation competence of family practice
      trainees in Kuwait.
AB  - BACKGROUND: No single approach to the regulatory assessment of global
      consultation competence has been shown to possess the required levels of
      validity, reliability and feasibility. OBJECTIVE: To evaluate the approach
      adopted in Kuwait to the regulatory end-point assessment of the global
      consultation competence of family practice trainees with particular reference to
      validity, reliability and feasibility. METHODS: Family practice trainees in
      Kuwait were individually and directly observed for 3 hours in consultation with a
      minimum of 10 patients by a pair of examiners. Performance was judged against the
      explicit criteria of consultation competence as contained in the Leicester
      Assessment Package (LAP). RESULTS: The marks independently allocated by the pairs
      of examiners to 126 trainees between 1994 and 2001 were within five percentage
      points on 91% of occasions. A reliability coefficient of 0.82 was achieved when
      two examiners independently marked candidates consulting with 10 real patients;
      this rose to 0.95 at the critical 50% pass-fail margin. The main sources of
      variance contributing to the reliability of marks allocated were candidate
      performance (42%) and the interaction of candidate performance across cases,
      i.e., case specificity (30%). The clinical challenges presented by the patients
      were judged by both examiners to be sufficient to enable performance to be
      assessed across the seven LAP consultation categories as follows: behaviour and
      relationship with patients (100% of consultations), interviewing/history taking
      (100%), record keeping (99%), patient management (99%), problem solving (98%),
      physical examination (95%), and anticipatory care (86%). Each assessment involved
      a pair of examiners and lasted approximately 3.5 hours. CONCLUSION: The Kuwait
      clinical examination achieves high content validity and authenticity as it uses
      direct observation of performance, validated and explicit criteria against which
      performance is judged, and real patient challenges. It can discriminate between
      different levels of consultation performance and satisfies the recognized
      reliability threshold for regulatory examinations (0.82 vs 0.80). Accordingly, we
      recommend the use of such an approach in the regulatory end-point assessment of
      the global consultation competence of trainees in family practice. Such an
      approach is more valid, and is likely to be more feasible, than simulated
      surgeries or the short-case OSCE format.

PMID- 17002958
TI  - WHO diagnostic criteria as a validation tool for the diagnosis of diabetes
      mellitus: a study in five European countries.
AB  - OBJECTIVE: In 1999, the World Health Organization (WHO) published new diagnostic
      criteria for diabetes mellitus (DM). The cut-off value of the fasting plasma
      glucose concentration was lowered from 7.8 to 7.0 mmol/l. The WHO criteria were
      used to validate the diagnosis made by the general practitioner, and to compare
      the diagnostic validity of diabetes mellitus in different countries. METHODS: We
      retrospectively analysed 2556 newly diagnosed diabetics. Incidence was calculated
      according to the 1999 WHO criteria. Data were collected in general practice
      networks in five European countries or regions (Belgium, England, the
      Netherlands, Portugal, Spain). RESULTS: According to the WHO criteria, 82% of the
      cases were valid diagnoses. Compared to the total group, in Spain, significantly
      more diagnoses were in agreement with the WHO criteria, whereas this number was
      significantly lower in England and Portugal. From the patients whose diagnosis
      was not in agreement with the WHO criteria, significantly more were women than
      men. CONCLUSION: By using the WHO diagnostic criteria, the international
      standard, as a validation tool, we show that the diagnoses of diabetes mellitus
      made in primary care are valid. Furthermore, we show that these diagnoses are
      comparable between countries. Therefore, information from general practice
      registration networks is a valuable and valid source for international
      comparisons.

PMID- 17002959
TI  - Association of diagnosis of ischaemic heart disease, diabetes mellitus and heart
      failure with cognitive function in the elderly population.
AB  - OBJECTIVE: The aim of this study was to describe the association between
      ischaemic heart disease (IHD), diabetes mellitus (DM) and heart failure (HF) and
      the prevalence of cognitive impairment. METHODS: In a cross-sectional, community
      based study in Karlskrona, Sweden, 1402 participants of the Swedish National
      Study on Ageing and Care (60-96 y) underwent a medical examination and
      psychological testing including the Mini Mental State Examination (MMSE). Of
      these, 58% stated that they were treated for hypertension, IHD, DM or HF, or had
      ECG abnormalities (positive screen). RESULTS: The prevalence of cognitive
      impairment (MMSE score < 24) in patients treated for IHD, DM or HF was 28.5%
      compared to 16.1% in the population with a negative screen without cardiovascular
      disease or DM. After stratification by age, the difference was seen to be due to
      a higher prevalence of cognitive impairment in the age group 70-79 y, where 68.8%
      of the cognitively impaired came from the group treated for IHD, DM or HF. The
      odds ratio for cognitive impairment in this age group was 4.4 (95% CI 1.7-11.4),
      when compared to those with a negative screen as baseline. CONCLUSION: This study
      has shown that the patient group treated for IHD, DM or HF has a higher
      prevalence of cognitive impairment and a higher risk of developing early
      cognitive impairment between the ages of 70 and 79 y. Although this study has not
      provided conclusive evidence that cardiovascular disease and DM are associated
      with the early development of cognitive impairment, it provides incentive for
      further studies.

PMID- 17002960
TI  - A future career in general practice? A longitudinal study of medical students and
      pre-registration house officers.
AB  - OBJECTIVE: To monitor the future career preferences of medical students
      throughout their undergraduate years and into their postgraduate career, and to
      evaluate which factors may influence career choice intentions, and when this
      happens, over time. DESIGN: Longitudinal study. METHODS: Questionnaire to all
      Aberdeen, United Kingdom, Medical School entrants in 1996, and five annual follow
      ups (four undergraduate, one postgraduate). RESULTS: Response rates: year 1,
      100%; year 2, 78%; year 3, 70%; year 4, 64%; year 5, 65%; pre-registration house
      officer (PRHO), 60%. Throughout the study, females were more positive about a
      career in general practice. General practice was the first choice for 13% of
      students in year 1; year 2, 9%; year 3, 22%; year 4, 24%; year 5, 27%; PRHO, 29%.
      Those choosing general practice were more likely than those choosing other
      specialties to be female, have their family home in Scotland, rate their academic
      abilities lower and their non-academic abilities as average, and have decided on
      their future career earlier. Reasons for general practice included: working in
      and being part of a community; continuity of patient contact; variety of
      illnesses and people encountered; undergraduate teaching experiences; dislike of
      or disillusionment with hospital medicine; and an increasing awareness of part
      time opportunities. CONCLUSION: As medical undergraduates progressed through the
      curriculum and became PRHOs, general practice became more popular as a career
      choice, particularly with females. This may be partly explained by the increased
      exposure to general practitioners and patients in the new community-based
      teaching programme and the increasing awareness of lifestyle advantages with the
      particular benefits of more regular hours and working part time.

PMID- 17002961
TI  - Specialist training of Slovene family physicians.
AB  - Family medicine in Europe started to develop in the 1960s with the introduction
      of obligatory specialist training. Slovenia is a country with a long tradition of
      family medicine specialist training, but up until 2002 this was neither
      elaborated on nor conducted by peers in general practice/family medicine. When
      the country's socialist system started to transform due to political reforms,
      Slovenia began to modify its system in order to meet the criteria of the European
      Union. One of the changes was the introduction of a new healthcare system with an
      influential Medical Chamber responsible for postgraduate training in all
      specialities. A new model for vocational training in family medicine was
      established in 2002, following the recommendations of the European Union of
      General Practitioners (UEMO). According to the new programme, which lasts 4
      years, trainees spend half of their training in a hospital setting and half in
      general practice, where they are supervised by a trainer in practice. This
      article describes the legal process of introducing new forms of specialist
      training in Slovenia, and its content. CONCLUSION: A comparison with UEMO
      countries shows that the new model is comparable to other countries.

PMID- 17002962
TI  - Emergency hospital admission for pain in palliative patients: a crucial role for
      general practitioners.

PMID- 17002963
TI  - Yield of abdominal ultrasound in patients with abdominal pain referred by general
      practitioners.

PMID- 17002964
TI  - How general practitioners can manage work-related psychological complaints.
      Design and pilot of a guideline: a contribution towards solving a huge problem.

PMID- 17002965
TI  - Physical inactivity of Italian general practitioners.

PMID- 17002967
TI  - Pharmacokinetic consequences of pegylation.
AB  - Pegylation, generally described as the molecular attachment of polyethylene
      glycols (PEGs) with different molecular weights to active drug molecules or
      surface treatment of drug-bearing particles with PEGs, is one of the most
      promising and extensively studied strategies with the goal of improving the
      pharmacokinetic behavior of the therapeutic drugs. A variety of PEGs, both linear
      and branched, with different molecular weights have been exploited successfully
      for use in this procedure in the form of reactive PEG species. Both reversible
      and irreversible PEG-drug conjugates have been prepared with relative
      advantages/disadvantages. The main pharmacokinetic outcomes of pegylation are
      summarized as changes occurring in overall circulation life-span, tissue
      distribution pattern, and elimination pathway of the parent drug/particle. Based
      on these favorable pharmacokinetic consequences leading to desired
      pharmacodynamic outcomes, a variety of proteins/peptides as well as small
      molecule drugs have been pegylated and evaluated successfully. Also a number of
      corresponding products have been approved by the U.S. FDA for specific clinical
      indications and some others are underway. In this article, the chemistry,
      rationale, strategies, pharmacokinetic outcomes, and therapeutic possibilities of
      pegylated drugs are reviewed with pharmacokinetic aspects presented with more
      details.

PMID- 17002969
TI  - Pectin/zein beads for potential colon-specific drug delivery: synthesis and in
      vitro evaluation.
AB  - Novel complex hydrogel beads were prepared from two edible polymers: pectin, a
      carbohydrate from citrus fruits, and zein, a protein from corn. The pectin/zein
      complex hydrogels did not swell in physiological environments, but hydrolyzed in
      the presence of pectinases. An in vitro study showed the capacity of the
      hydrogels to endure protease attack and residence time variation. The physical
      and biological properties of the new hydrogels were attributed to molecular
      entanglement of the two polymers. The pectin networks were stabilized by the
      bound zein molecules. In turn, the pectin networks shielded the bound zein from
      protease digestion.

PMID- 17002968
TI  - Evaluation of ex vivo human skin permeation of genistein and daidzein.
AB  - The percutaneous absorption of genistein (GEN) and daidzein (DAI), whose
      oestrogenic-like activity is well known, is scantily investigated. In this work
      the ability of GEN and DAI to reach therapeutic steady-state plasma
      concentrations following transdermal administration was studied. The skin
      permeation studies were conducted by using modified Franz diffusion cell and
      human epidermis as a membrane. PEG400 was the most effective vehicle for both
      molecules. On the basis of the ex vivo permeation results and estimating
      therapeutic plasma concentration, we assume that pure GEN can be efficaciously
      administered by the transdermal route.

PMID- 17002970
TI  - Effect of different terpene-containing essential oils on percutaneous absorption
      of trazodone hydrochloride through mouse epidermis.
AB  - The aim of our study was to investigate the enhancing effect of several essential
      oils in the percutaneous absorption of trazodone hydrochloride (TZN). For this
      purpose, fennel oil, eucalyptus oil, citronella oil, and mentha oil were applied
      on the skin membrane in three different ways: included in the transdermal device,
      as a pretreatment, or both. To investigate the effect of penetration enhancers
      used in this study on the percutaneous absorption of TZN through mouse epidermis,
      Keshary-Chien diffusion cells were employed. The receptor phase was constantly
      stirring saline phosphate buffer of pH 7.4 at 37 +/- 1 degrees C. Results showed
      that pretreatment of skin with essential oils increases the flux values of TZN
      compared with the values obtained when the same essential oils were included in
      the transdermal devices. The percutaneous penetration flux for TZN was increased
      with skin pretreatment by 10% essential oils in the following order: fennel oil >
      eucalyptus oil > citronella oil > mentha oil. The amount of TZN retained in the
      skin after pretreatment with essential oils was found to be very similar in all
      cases and much higher than in the experiments without skin pretreatment.

PMID- 17002971
TI  - Synthesis of chlorambucil-tempol adduct and its delivery using fluoroalkyl double
      ended poly (ethylene glycol) micelles.
AB  - In our pursuit to find potent anticancer drugs, we have covalently bonded free
      radical tempol to chlorambucil giving a chlorambucil-tempol (CT) adduct in which
      both of the anticancer active sites in tempol and chlorambucil were left intact.
      Analysis using NMR, Maldi-TOF, and EPR verified the designed chemical structure.
      Because the CT adduct is more hydrophobic than chlorambucil, its delivery also
      was investigated using fluoroalkyl double-ended poly (ethylene glycol) (Rf-PEG)
      micelles. Results from EPR spectra and(19) F and(1) H NMR spin lattice relaxation
      times show that the Rf-PEG micelles are able to encapsulate CT into the Rf cores
      of the micelles.

PMID- 17002972
TI  - Combined use of polycationic peptide and biodegradable macromolecular polymer as
      a novel gene delivery system: a preliminary study.
AB  - Plasmid(p) DNA was condensed by polycationic peptide polylysine (PLL) to be a
      core and then encapsulated in biodegradable monomethoxy (polyethyleneglycol)
      poly(lactide-co-glycolide)-monomethoxy (poly-ethylene glycol) (PELGE) to form
      core-shell nanoparticles as a novel gene delivery system PPD (PELGE-PLL-DNA).
      Nanoparticles formed from PPD had several complementary properties such as
      improved biocompatibility, decreased cytotoxicity, enhanced pDNA integrity, and
      the characteristic of lysosomal escape as PLGA nanoparticles. The results
      demonstrated the potential of this PPD as an efficient gene delivery system.

PMID- 17002973
TI  - Characterization of PLGA microparticles as a drug carrier for 3-ethoxycarbonyl-2h
      benzofuro[3,2-f]-1-benzopyran-2-one. Ultrastructural study of cellular uptake and
      intracellular distribution.
AB  - Here we describe the application of microparticles (MPs) for the delivery and
      release of the drug a benzopsoralen. We also evaluated the intracellular
      distribution and cellular uptake of the drug by using an encapsulation technique
      for therapeutic optimization. MPs containing the compound 3-ethoxycarbonyl-2H
      benzofuro[3,2-f]-1-benzopyran-2-one (psoralen A) were prepared by the solvent
      evaporation technique, and parameters such as particle size, drug encapsulation
      efficiency, effect of the encapsulation process on the drug's photochemistry,
      zeta potential, external morphology, and in vitro release behavior were
      evaluated. The intracellular distribution of MPs as well as their uptake by
      tissues were monitored. Size distribution studies using dynamic ligh scattering
      and scanning electron microscopy revealed that the MPs are spherical in shape
      with a diameter of 1.4 micro m. They present low tendency toward aggregation, as
      confirmed by their zeta potential (+10.6 mV). The loading efficiency obtained was
      75%. As a consequence of the extremely low diffusivity of the drug in aqueous
      medium, the drug release profile of the MPs in saline phosphate buffer (pH 7.4)
      was much slower than that obtained in the biological environment. Among the
      population of peritoneal phagocytic cells, only macrophages were able to
      phagocytose poly-d,l-lactic-co-glycolic acid (PLGA) MP. The use of psoralen A in
      association with ultraviolet light (360 nm) revealed morphological
      characteristics of cell damage such as cytoplasmic vesiculation, mitochondria
      condensation, and swelling of both the granular endoplasmatic reticulum and the
      nuclear membrane. These results indicate that PLGA MP could be a promising
      delivery system for psoralen in connection with ultraviolet irradiation therapy
      (PUVA).

PMID- 17002977
TI  - Catalytic mechanism and substrate selectivity of aldo-keto reductases: insights
      from structure-function studies of Candida tenuis xylose reductase.
AB  - Aldo-keto reductases (AKRs) constitute a large protein superfamily of mainly
      NAD(P)-dependent oxidoreductases involved in carbonyl metabolism. Catalysis is
      promoted by a conserved tetrad of active site residues (Tyr, Lys, Asp and His).
      Recent results of structure-function relationship studies for xylose reductase
      (AKR2B5) require an update of the proposed catalytic mechanism. Electrostatic
      stabilization by the epsilon-NH3+ group of Lys is a key source of catalytic power
      of xylose reductase. A molecular-level analysis of the substrate binding pocket
      of xylose reductase provides a case of how a very broadly specific AKR achieves
      the requisite selectivity for its physiological substrate and could serve as the
      basis for the design of novel reductases with improved specificities for
      biocatalytic applications.

PMID- 17002978
TI  - RNase L: its biological roles and regulation.
AB  - 2'-5'oligoadenylate-dependent ribonuclease L (RNase L) is one of the key enzymes
      involved in the function of interferons (IFNs), a family of cytokines
      participating in innate immunity against viruses and other microbial pathogens.
      Upon binding with its activator, 5'-phosphorylated, 2'-5' linked oligoadenylates
      (2-5A), RNase L degrades single-stranded viral and cellular RNAs and thus plays
      an important role in the antiviral and antiproliferative functions of IFNs. In
      recent years, evidence has revealed that RNase L displays a broad range of
      biological roles which are summarized in this review.

PMID- 17002979
TI  - Chemical synthesis and biosynthesis of the cyclotide family of circular proteins.
AB  - Cyclotides are a recently discovered class of proteins that have a characteristic
      head-to-tail cyclized backbone stabilized by a knotted arrangement of three
      disulfide bonds. They are exceptionally resistant to chemical, enzymatic and
      thermal treatments because of their unique structural scaffold. Cyclotides have a
      range of bio-activities, including uterotonic, anti-HIV, anti-bacterial and
      cytotoxic activity but their insecticidal properties suggest that their natural
      physiological role is in plant defense. They are genetically encoded as linear
      precursors and subsequently processed to produce mature cyclic peptides but the
      mechanism by which this occurs remains unknown. Currently most cyclotides are
      obtained via direct extraction from plants in the Rubiaceae and Violaceae
      families. To facilitate the screening of cyclotides for structure-activity
      studies and to exploit them in drug design or agricultural applications a
      convenient route for the synthesis of cyclotides is vital. In this review the
      current chemical, recombinant and biosynthetic routes to the production of
      cyclotides are discussed.

PMID- 17002980
TI  - Sensorineural hearing loss: potential therapies and gene targets for drug
      development.
AB  - Recent advances in the developmental biology, genetics and cell biology of the
      inner ear are guiding research to novel therapeutic modalities - a market
      currently estimated to be at least US Dollars 10 billion. This article highlights
      prospects to manipulate the mammalian hearing organ with gene and stem cell
      delivery to the inner ear to protect, repair or regenerate the hair cells,
      supporting cells and associated nerves.

PMID- 17002981
TI  - Lysosomal labilization.
AB  - The lysosomal compartment is the place for cellular degradation of endocytosed
      and autophagocytosed material and a center for normal turnover of organelles as
      well as most long-lived proteins. Lysosomes were long considered stable
      structures that broke and released their many hydrolytic enzymes only following
      necrotic cell death. It is now realized that lysosomes instead are quite
      vulnerable, although in a heterogeneous way. Their exposure to a number of
      events, such as oxidative stress, lysosomotropic detergents and aldhydes, as well
      as overexpression of the p53 protein, causes time-and-dose-dependent lysosomal
      rupture that is followed by apoptosis or necrosis. Partial lysosomal rupture has
      often been found to be an early upstream event in apoptosis, while necrosis
      results from fulminant lysosomal rupture. Consequently, factors influencing the
      stability of lysosomes, for instance their content of labile and redox-active
      iron, seem to be essential for the survival of cells.

PMID- 17002982
TI  - Differential gene expression in skeletal muscle of rats with vitamin E
      deficiency.
AB  - Vitamin E (VE) deficiency is accompanied by myopathy in various animal species
      including man. Although gene expression profiles related to degenerative and
      regenerative processes in different kinds of myopathies have been studied, no
      global expression profile for skeletal muscle subject to VE deficiency has
      previously been reported. In the present study, Affymetrix GeneChip technology
      was used to obtain such a profile. Two groups of male rats were fed with either a
      diet deficient in VE or a control diet. Differential gene expression was
      monitored at five time-points over 430 days, with all animals individually
      profiled. Out of approximately 7000 genes represented on the Genechip, 56 were
      found to be up-regulated in response to VE deficiency in at least four
      consecutive time-points from as early as 91 days of deficiency. Up-regulated
      genes included muscle structure and extra cellular matrix genes, as well as anti
      oxidative, anti-inflammatory and anti-fibrotic genes. Our data show that
      molecular transcription might provide a very early marker to detect oncoming
      degenerative conditions in VE deficiency. They provide further insight into
      possible molecular mechanisms underlying VE deficiency in skeletal muscle, and
      reveal the activation of an intensive protection program that can explain the
      long maintenance of muscle structure during deficiency.

PMID- 17002983
TI  - Thermodynamic analysis of three state denaturation of Peanut Agglutinin.
AB  - Peanut Agglutinin (PNA) is a homotetrameric protein with a very unusual open
      quaternary structure. During denaturation, it first dissociates into a molten
      globule like state, which subsequently undergoes complete denaturation. Urea
      denaturation of PNA at neutral pH has been studied by intrinsic fluorescence
      spectroscopy and has been fitted to a three state model, A4 <=> 4I <=> 4U, to get
      all the relevant thermodynamic parameters. Urea denaturation leads to continuous
      red shift of wavelength maxima. The molten globule like state is formed in a
      short range of urea concentration. Refolding of the denatured PNA has been
      attempted by intrinsic fluorescence study. Refolding by instantaneous dilution
      shows the occurrence of the formation of an intermediate at a relatively rapid
      rate, within few seconds. The transition from PNA tetramer to molten globule like
      state is found to have a DeltaG value of approximately 33 kcal/mole while it is
      approximately 8 kcal/mole for the transition from molten globule like state to a
      completely denatured state. This in turn indicates that the tetramerization in
      PNA contributes significantly to the stability of the oligomer.

PMID- 17002984
TI  - Do aminoacyl-tRNA synthetases have biological functions other than in protein
      biosynthesis?

PMID- 17002985
TI  - How I became a Biochemist.

PMID- 17002986
TI  - Addiction and sexually transmitted disease (STD), human immunodeficiency virus,
      (HIV), and acquired immune deficiency syndrome (AIDS): their mutual interactions.
AB  - We explore the links between substance use, misuse, addiction, and dependency1
      and sexuality, sexually transmitted diseases (STD), human immunodeficiency virus
      (HIV), and acquired immune deficiency syndrome (AIDS) to increase our awareness
      of their interdependence and to identify new ways to perceive, judge, and
      intervene (or not to) with associated problems. We consider the sociocultural and
      economic context in which these behaviors occur; the impact these behaviors have
      on one another; the personal opinions and attitudes; the religious, moral, or
      political beliefs and agendas; the physiological and fiscal constraints; and
      theories of rational decision-making and psychological motivation that act to
      increase or reduce the incidence of these behaviors and their sequellae, while
      hindering or facilitating prevention, harm reduction, and treatment
      interventions. Mechanisms of epidemic spread of STDS/HIV/AIDS are presented in
      the Appendix. Each of these terms are loaded "container concepts" that are
      culture-bound and stakeholder-driven and whose dimensions are less than consensus
      based. They represent a range of meanings, uses, and misuses in an ongoing
      politicalized area of human and systemic functioning and adaptations.

PMID- 17002988
TI  - Beyond needle sharing: meta-analyses of social context risk behaviors of
      injection drug users attending needle exchange programs.
AB  - This study gathered data from U.S. and international needle exchange programs
      (NEPs). Of particular interest were outcome measures of dependent variables
      related to behaviors within social contexts of injection drug users (IDUs), an
      area not well understood. Thirty-one studies, with a total of 86 separate
      measures of 36 dependent variables were included. Because combining all results
      into a single meta-analysis would be inappropriate, dependent variables were
      placed into five categories for five separate meta-analyses: risky contexts,
      injection frequency, sharing drug paraphernalia, drug preparation, and syringe
      use. NEP attendance was inversely related to declines in all categorical
      behaviors except for "risky context." NEP attenders are slightly more likely to
      be in a risky circumstance when injecting drugs than non-attenders. While
      injection frequency declined only slightly among NEP attenders, that result may
      be interpreted as a positive outcome, given the often-stated criticism that
      providing clean needles encourages increased drug use. NEP use was weakly
      associated with a decrease in the sharing of drug paraphernalia. Clean needles
      alone do not appear to be sufficient motivation to motivate major changes in
      contextual risk behaviors analyzed herein. Research is needed to assess the
      impact of interpersonal IDU relationships with other stakeholders (clinic
      employees, van drivers, medical personnel, nutritionists, sexual partners, etc.)
      on IDU drug-using behaviors at many levels.

PMID- 17002989
TI  - Drug interactions between psychoactive substances and antiretroviral therapy in
      individuals infected with human immunodeficiency and hepatitis viruses.
AB  - The liver disease characteristic of alcohol dependence encompasses three main
      related entities: steatosis, alcoholic hepatitis, and cirrhosis. Alcoholic
      cirrhosis is a leading cause of global morbidity and mortality. Alcohol intake
      among injecting drug users is a major contributor to transmission of viral
      infections, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV),
      and hepatitis C viruses (HCV). HIV and HCV coinfected patients develop liver
      diseases earlier and more severely than the monoinfected individuals, including
      hepatocellular carcinoma. Interactions exist between the therapeutic drugs used
      to minimize and control the drug and alcohol dependence. Furthermore, drug-drug
      interactions occur between the highly active antiretroviral therapy (HAART) and
      alcohol, different HAART components and methadone, or each one of the therapies
      with the other, thus contributing to a higher toxicity level. With the evolution
      of effective antiretroviral therapy, survival of persons with HIV, and the
      syndrome it causes, acquired immunodeficiency syndrome (AIDS) has increased
      dramatically. Drug-drug interactions may appear between alcohol and anti-HBV or
      anti-HCV, therapy in the presence or absence of anti-HIV therapy. Several other
      medical-, social-, and drug-related factors of this population have to be
      considered when providing HAART. Because many coinfected patients also have
      problems with substance use, dealing with their drug dependence is an important
      first step in an attempt to improve adherence to and tolerance of antiviral
      therapy. It is necessary to minimize the risk of liver disease acceleration
      and/or reinfection with hepatitis viruses. Knowledge of potential drug
      interactions between methadone, antiretroviral therapy, psychoactive drugs, and
      antipsychotics and the role of coinfection with HBV or HCV and the drugs used in
      eradicating viral hepatitis permits suitable antiretroviral combinations.

PMID- 17002987
TI  - Behavior change and health-related interventions for heterosexual risk reduction
      among drug users.
AB  - Prevention of heterosexual transmission of HIV between and from drug users is
      important for controlling the local and global HIV heterosexual epidemic. Sex
      risk reduction interventions and health-related interventions are important for
      reducing the sex risk behaviors of drug users. Sex risk reduction interventions
      address individual-level, peer-level, and structural-level determinants of risk
      reduction. Health-related interventions include HIV counseling and testing,
      prevention and treatment of sexually transmitted diseases, and delivery of highly
      active antiretroviral therapy. It is important to adapt effective interventions
      implemented in resource-rich countries to the realities of the resource
      constrained settings and to address relevant contextual factors.

PMID- 17002990
TI  - Expanding research on the role of alcohol consumption and related risks in the
      prevention and treatment of HIV/AIDS.
AB  - This article is a review of some of the major epidemiological, behavioral,
      biological, and integrative prevention research issues and priorities in the area
      of HIV/AIDS and alcohol consumption. Drinking alcohol increases both the risk for
      infection with HIV and related illnesses and the morbidity and mortality of
      patients who progress to AIDS. New and improved measurement procedures have
      helped in assessment of the complex patterns of alcohol use, identification of
      intervening explanatory mechanisms for risk behaviors and contexts, and
      determination of intervention outcomes. Both the direct and indirect effects of
      alcohol misuse appear to be major contributors to both the risk for infection
      with HIV and the transmission of HIV/AIDS at the individual and population
      levels. There is increasing evidence that perhaps no level of alcohol consumption
      is "safe" for those who are HIV infected and receiving antiretroviral treatment.
      Interdisciplinary basic behavioral and biomedical research is needed to develop
      comprehensive culturally appropriate strategies for programs that can be
      effectively delivered in community contexts in the United States and abroad and
      that focus on the integration of our understanding of individual behaviors, high
      risk group membership, biological mechanisms, and the social and physical
      environments that place individuals at risk for HIV infection. High-priority
      topics include improving adherence to antiretroviral medications, prevention of
      infection in young minority women in the United States, and treatment of HIV+
      pregnant women who are alcohol abusers to prevent adverse fetal outcomes, which
      is an international focus in under-resourced settings in Africa.

PMID- 17002991
TI  - The relationship between HIV/Sexually Transmitted Infection risk and alcohol use
      during commercial sex episodes: results from the study of female commercial sex
      workers in the Philippines.
AB  - The HIV/Sexually Transmitted Infection (STI) risk associated with alcohol use
      between female commercial sex workers (FCSWs) and their customers has been
      understudied. We examined this relationship for 1,114 FCSWs aged 15-54 with data
      collected during the baseline study period (1994 to 1998) in four southern
      provinces of the Philippines. Two alcohol-related risk situations during
      commercial sex episodes were examined: prior alcohol use by an FCSW and perceived
      intoxication in a customer. The influence of sociodemographic variables on sexual
      risk behaviors was also studied. Multiple sexual risk behaviors were observed
      with more frequency for FCSWs if alcohol was used before commercial sex or if the
      episode involved a customer perceived to be intoxicated. Forty-two percent of
      FCSWs who had sex with an intoxicated customer were STI positive, significantly
      more than FCSWs who did not have sex with an intoxicated customer (28%, p < .01).
      Similar significant differences were found for FCSWs who did not consume alcohol
      before having sex and were STI positive (29%) versus FCSW who did consume alcohol
      before sex and were STI positive (33%, p < .01). Our analyses reinforce
      accumulating evidence in the field that sexual risk reduction interventions need
      to go beyond the behaviors of individual FCSWs to meet the layering of risks such
      as observed in this study. Multilevel strategies targeting customer substance use
      and other situational and structural factors have proven to be pivotal mediators
      in our other research with this population. These experiences and the limitations
      of this study are discussed.

PMID- 17002993
TI  - Club drugs as causal risk factors for HIV acquisition among men who have sex with
      men: a review.
AB  - We reviewed medical and psychology databases for articles published between
      January 1980 and August 2005 demonstrating associations between HIV/Sexually
      Transmitted Infection risk and club drug use. Seventy-four articles were
      reviewed, of which 30 provided adjusted risk ratios for associations between
      HIV/sexually transmitted infection risk and club drug use among men who have sex
      with men. Definitions and lists of club drugs were broad and inconsistent. We
      constructed a conceptual framework of biologically plausible pathways for
      causation. Using Hill's criteria to examine club drugs as causal risk factors for
      HIV, we found the most evidence for methamphetamine and volatile nitrites;
      however, more studies are needed.

PMID- 17002992
TI  - Comparison of sexual and drug use behaviors between female sex workers in Tijuana
      and Ciudad Juarez, Mexico.
AB  - Female sex workers (FSWs) have been documented to have high rates of sexually
      transmitted diseases and HIV in many parts of the world. However, little work has
      been done to characterize the prevalence of these infections along the U.S.
      Mexican border, where sexual tourism and culturally sanctioned sex work among
      nationals is widespread. The objective of this study was to compare differences
      in background characteristics, HIV risk behaviors, drug use, and sexually
      transmitted infection/HIV prevalence between FSWs who participated in a
      behavioral risk intervention in two U.S.-Mexican border cities. Baseline data
      were collected from March 2004 through September 2005. Data from 295 FSWs were
      compared between Tijuana and Ciudad (Cd.) Juarez. Among 155 FSWs in Tijuana and
      140 in Cd. Juarez, HIV seroprevalence was 4.8% and 4.9%, respectively. FSWs in
      Cd. Juarez were more likely to test positive for active syphilis (31.3%) compared
      with Tijuana (11.8%) but did not differ in terms of the prevalence of gonorrhea
      and chlamydia. FSWs in both sites reported high levels of unprotected sex and use
      of drugs; however, FSWs in Cd. Juarez were more likely than those in Tijuana to
      ever have injected drugs (75% vs. 25%, p <.001). Heroin and cocaine use and
      injection drug use were significantly more common in Cd. Juarez, whereas
      methamphetamine use was more common in Tijuana. Injection of vitamins was common
      in both cities. Logistic regression analyses suggested that being younger,
      working in Cd. Juarez, and using heroin or cocaine were independently associated
      with active syphilis infection. In Tijuana, methamphetamine use was strongly
      associated with active syphilis infection. These preliminary results suggest that
      risk profiles for HIV/sexually transmitted infection among FSWs in these two
      Mexico-U.S. border cities differ, suggesting a need to tailor interventions to
      the specific needs in each city.

PMID- 17002994
TI  - Impact of a harm-reduction policy on HIV and hepatitis C virus transmission among
      drug users: recent French data--the ANRS-Coquelicot Study.
AB  - In France a harm-reduction policy was implemented in the late 1980s with the aim
      of reducing the prevalence of HIV and hepatitis C virus (HCV) infection among
      drug users. The ANRS-Coquelicot survey was designed to measure the prevalence of
      HIV and HCV infection among drug users and to examine determinants of at-risk
      behaviors. In 2002, information was collected from 166 drug users recruited in
      all types of services specializing in drug use intervention and harm reduction in
      Marseille, France. Self-reported HIV and HCV serostatus was compared with the
      results of serological tests done on capillary blood collected on filter paper.
      The self-reported and biologically documented prevalence rates of HIV infection
      were identical (22%). In contrast, the self-reported prevalence of HCV infection
      was 52%, whereas the biologically documented prevalence was 73%. Overall, 30% of
      HCV-infected drug users were unaware of their status. Forty-four percent of drug
      users under 30 years of age were HCV seropositive, suggesting that they had been
      infected early during drug use. The harm-reduction policy seems to have had a
      marked impact on HIV transmission among drug users but a much more limited impact
      on HCV transmission. The limitations and implications of the study are discussed.

PMID- 17002995
TI  - Age shift in patterns of injection drug use among the HIV/AIDS population in
      Miami-Dade County, Florida.
AB  - Analysis of HIV exposure category for 20,034 persons in three age groups (13-29,
      30-49, 50 and over) who were alive through 2003 and had been reported to the
      Florida Department of Health with HIV or AIDS in Miami-Dade County, Florida,
      found that having a history of injection drug use increases with increasing age
      (p < .001). Consideration of age-specific HIV risk profiles has implications for
      primary and secondary HIV prevention interventions, planning, and policy.

PMID- 17002996
TI  - Complex emergencies, HIV, and substance use: no "big easy" solution.

PMID- 17002998
TI  - Adrenal incidentaloma (adrenaloma).
AB  - The management of adrenalomas should include the following: 1. A detailed history
      and physical examination to detect subtle evidence of hormonal hypersecretion or
      the possibility of metastatic carcinoma. 2. Hormonal studies: Short dexamethasone
      suppression test (2 mg of dexamethasone) followed by a high-dose dexamethasone
      suppression test (8 mg), CRH assay and analysis of the diurnal cortisol rhythm if
      serum cortisol value post dexamethasone is greater than 3 microg/dL, 24-hour (or
      spot) urinary catecholamine metabolites (metanephrine and normetanephrine), In
      the hypertensive or normotensive patient with serum potassium less than 3.9
      nmol/L, the upright aldosterone level to plasma renin activity (PRA) ratio. 3.
      Additional studies, such as: Glucose tolerance test, Bone mineral density
      evaluation, Body composition and fat distribution by DEXA (Dual energy X-Ray
      absorptiometry). The role of FNA is limited. It may be helpful only in the
      patient with coexistent extradrenal carcinoma to confirm adrenal metastasis.
      Although genetic and molecular biology studies do not have wide clinical
      application, they should be encouraged and supported. Once all of these data are
      collected, the recommendations are: 1. All clearly nonfunctioning adrenalomas
      that are not suspicious for malignancy in asymptomatic patients should be
      observed for several years, mainly with hormonal studies, until their secretory
      and benign nature is confirmed. 2. All patients with adrenalomas and evidence of
      subclinical function, suspicion for malignancy (using size, imaging, FNA and
      molecular biology criteria) and symptoms, such as hypertension, obesity, impaired
      glucose tolerance, central fat deposition and reduced bone mineral density,
      should undergo laparoscopic adrenalectomy. The age, the overall medical condition
      and the anxiety of the patient should also be considered in the decision to
      operate on a patient with an adrenaloma.

PMID- 17002999
TI  - Prediction and prevention of type 2 diabetes.
AB  - Type 2 diabetes mellitus is one of the most costly and burdensome chronic
      diseases of our time and a condition that is increasing in epidemic proportions
      worldwide. Its complications are a significant cause of morbidity and mortality
      and a tremendous economic burden to the society. Effective prevention programs
      are therefore urgently needed. Some of the risk factors for the development of
      type 2 diabetes, such as obesity, physical inactivity and high-fat diet, can
      potentially be modified. Compelling evidence now exists from well designed
      randomized studies that the disease can be prevented or delayed in subjects at
      high risk for its development, i.e. subjects with impaired glucose tolerance
      (IGT) or impaired fasting glucose (IFG). The interventions studied include
      lifestyle modifications (with diet and exercise) and drug treatment. Weight loss
      with lifestyle modification seems to be the most effective way so far, given the
      fact that it addresses other cardiovascular disease risk factors as well. The big
      challenge we are facing now is to try to implement these findings in our society
      or among our high-risk patients, taking into consideration the great difficulties
      involved in changing lifestyle and in maintaining lifestyle modifications.

PMID- 17003000
TI  - Doping: a challenge to the endocrinologist. A reappraisal in view of the Olympic
      Games of 2004.
AB  - The aim of this review is to provide an update on drug abuse by athletes, their
      mode of action and the technical difficulties of detection. The most common
      doping agents are the anabolic steroids (AS), testosterone derivatives modified
      to take advantage of the anabolic rather than the androgenic properties of the
      hormone. However, there are numerous side-effects that discourage their use.
      Several other substances and hormones, GH and rhEPO are currently used alone or
      combined to enhance performance. The diversity in nature of the substances used
      requires a constant alertness of physicians to detect drug abuse in sports.
      Doping is not limited to the professional athletes. It seems to be a generalized
      phenomenon that reflects modern society's concept of success. Therefore, the
      campaign to eradicate doping must also focus on individual responsibility. Since
      modern-day doping is strongly related to hormonal preparations, endocrinologists
      may play a pivotal role in providing information, protecting athletes' health
      and, moreover, retaining the ethical value of sport.

PMID- 17003001
TI  - Body composition in asymptomatic HIV-infected men: cross-sectional and
      prospective assessment.
AB  - Data on body composition changes in HIV infected patients is sparse and
      controversial. The aim of this study was to assess body composition in
      asymptomatic HIV-infected men with normal body weight in comparison to healthy
      HIV-negative control men and to investigate possible body composition changes in
      HIV-positive patients over a 2-year observation period. One hundred eight
      asymptomatic seropositive men, aged 19-62 years, and 20 healthy sex, age and
      weight - matched controls were recruited for the cross-sectional part of the
      study. Fifty-eight of the HIV+ patients were followed up for 2 years. Body
      weight, BMI, Bone Mineral Content (BMC), body Fat mass (Fat), % Fat, body Lean
      mass (Lean) and % Lean was recorded for each subject at the beginning and at the
      end of the follow-up period. The same analysis was repeated separately for arms,
      trunk and legs. HIV+ men had increased fat mass and reduced lean mass compared to
      controls (%Fat in HIV+ 24.3, %Fat in controls 19.2, p=0.012; %Lean in HIV+ 72.1,
      %Lean in controls 77.0, p=0.014). Lean mass was lower in extremities while fat
      mass was higher in the trunk region in HIV+ in comparison to controls,
      irrespective of antiretroviral therapy. Longitudinally, patients with higher
      baseline %Fat (>24.2, median) presented 20% decrease in fat mass while patients
      with lower baseline %Fat (< or =24.2) showed a smaller, non-significant decrease
      in fat mass accompanied by a significant decrease (2.52%) in lean mass. Fat loss
      occurred in all subjects predominantly in the extremities (16.5-36.45% loss),
      with relative preservation of trunk fat. It is concluded that otherwise
      asymptomatic HIV+ men exhibit subtle body composition changes involving reduced
      lean mass and increased central fat mass. The pattern of weight loss over time
      depends on baseline fat store: patients with adequate fat stores lose
      predominantly fat while patients with lower baseline fat stores lose both fat and
      lean mass. In the entire cohort, there is a tendency towards central adiposity,
      with the majority of fat being lost from the extremities, a picture resembling
      metabolic x syndrome.

PMID- 17003002
TI  - Self-reported prevalence of obesity among 20,329 adults from large territories of
      Greece, Serbia and Turkey.
AB  - The aim of this study was to investigate the prevalence of overweight, obesity
      and body mass index (BMI) distribution in people living in large territories of
      Greece, Serbia and Turkey. A cross-sectional multi-national epidemiological
      survey was designed on the basis of self-reported information on height and
      weight using the formula kg/m2. Overall, 20,329 individuals, aged 20-68 yrs,
      8,973 males and 11,356 females, participated in the study. Of these, 4,032 were
      selected from northern Greece, 10,069 from southwest Turkey and 6,228 from
      central Serbia. More specifically, participants from northern Greece were
      recruited from central Macedonia, from Southwest Turkey from the Kayseri region
      and from central Serbia from the greater Belgrade area. Our results showed that
      12.4% of the population studied was obese and 31.3% overweight. The corresponding
      figures for participants from Greece were 19.9% and 35.4%, from Turkey 12.0% and
      30.9% and from Serbia 8.2% and 29.4%, respectively. Overall, male participants
      had a higher mean BMI than females. However, Greek females were more obese in
      comparison with males. The opposite was true of the other two countries. Finally,
      in both males and females mean BMI tended to increase with age up to 50-59 years,
      and declined slightly thereafter. In conclusion, the overall prevalence of
      obesity and overweight in the Balkan peninsula does not differ from that reported
      in other European countries. However, BMI values between different countries of
      the Balkan peninsula are fairly variable, Greece leading in the prevalence of
      obesity with Serbia having the lowest prevalence of obesity. The data from this
      survey underline the need for health intervention aimed at preventing obesity,
      especially in Greece.

PMID- 17003003
TI  - The role of Hemochromatosis C282Y and H63D mutations in the development of type 2
      diabetes mellitus in Greece.
AB  - Several authors have suggested a positive association between diabetes type 2
      (DM2) and the C282Y and H63D mutations of the hereditary hemochromatosis gene but
      others have disputed it. There are also papers reporting an increased iron load
      in diabetes type 2 and a possible association with the pathogenesis of the
      disease. We therefore performed a study in 100 type 2 diabetics and 100 age and
      sex matched controls to assess the possibility that C282Y and H63D mutations
      constitute a risk factor for DM2 in Greece. We also evaluated the iron load in
      500 diabetes type 2 patients and 423 age and sex matched controls. We did not
      find any differences in the allele frequencies of the above mutations between
      patients with diabetes type 2 and controls. The allele frequencies were estimated
      to be 0.0075 for the C282Y and 0.115 for the H63D mutation. Subjects with even
      one mutation (C282Y or H63D) had higher transferrin saturation compared to those
      with no such mutations. This seems to apply to both diabetics (49+/- 8,6 vs
      44,5+/- 5,4, p<0,01) and controls (49,3+/- 7,3 vs 42,6+/- 3,3 p<0,01). Patients
      with DM2 had higher transferrin saturation compared to the general population.
      These differences were found among men (n=250, mean+/- SD 31,8+11 vs n=73, mean+/
      SD 29,5+8, p=0,05) as well as among women (n=250, mean+/- SD 28.5+10 vs n=350,
      mean+/- SD 25.5+9.6, p=0.001). The DM2 patients had higher ferritin levels
      compared to controls. In conclusion, DM2 patients have increased iron load. The
      C282Y and H63D mutations contribute to increased iron load in both DM2 and
      controls. There was no difference in the frequency of C282Y and H63D alleles
      between DM2 and controls in the Hellenic population.

PMID- 17003004
TI  - Insulin resistance in pheochromocytoma improves more by surgical rather than by
      medical treatment.
AB  - Pheochromocytoma, a neuroendocrine tumor, is often associated with hyperglycemia.
      To investigate the underlying pathogenetic mechanisms, five patients (3 women and
      2 men, aged 49+/-2.5, mean+/-SD) with benign adrenal pheochromocytoma were
      studied with an oral glucose tolerance test (OGTT) and the euglycaemic clamp
      technique. They were studied preoperatively without taking any medication (stage
      I), after taking an alpha adrenergic receptor blocking agent (stage II), after
      taking both an alpha and a beta adrenergic receptor blocking agent (stage III),
      and after surgical removal of the tumor (stage IV). Before any treatment, fasting
      blood glucose levels and glucose levels during the OGTT were pathologic in all
      patients. In all patients, mean glucose levels of the OGTTs performed at the
      three preoperative stages of the study were significantly higher than those of
      the OGTT performed postoperatively (ANOVA, alpha<0.05). Insulin levels during the
      OGTTs performed preoperatively peaked at 90 min while postoperatively they peaked
      at 60 min. No statistically significant difference was found among mean insulin
      levels during the OGTTs performed at all stages of the study. The clamp-based
      insulin sensitivity index (SI) improved progressively from stage I to IV of the
      study (ANOVA, alpha<0.05) (SIs of stages I, II, III, and IV were, respectively,
      3.23+/-0.9 (mean+/-SE), 3.79+/-0.7, 4.67+/-0.3, 6.38+/-1 (10(-4) dl/kg x min per
      microU/ml)). In conclusion, the pheochromocytoma-associated metabolic alterations
      of glucose homeostasis improved substantially only after removal of the tumor.
      The administration of alpha and beta adrenergic receptor blocking agents resulted
      in a slight but statistically significant improvement in glucose utilization
      whereas it completely normalized the cardiovascular manifestations of the
      disease. Thus, it is possible that either the dose of the adrenergic receptor
      blocking agent needed to control cardiovascular manifestations of
      pheochromocytoma is different than that needed for glucose metabolism
      normalization, or that other pheochromocytoma-associated factors may influence
      directly and/or indirectly carbohydrate homeostasis.

PMID- 17003005
TI  - Persistent hyperinsulinemic neonatal hypoglycemia caused by focal
      nesidioblastosis. Preoperative diagnosis by pancreatic venous sampling.
AB  - A female infant with persistent hyperinsulinemic hypoglycemia is described.
      Persistent euglycemia could not be achieved by diazoxide, somatostatin and
      frequent, low protein feeds. Preoperative localization of focal insulin
      hypersecretion by percutaneous pancreatic venous sampling allowed excision of
      only a small pancreatic portion which was followed by normalization of blood
      glucose levels.

PMID- 17003006
TI  - Baubo: a case of ambiguous genitalia in the Eleusinian mysteries.

PMID- 17003007
TI  - Growth and growth hormone secretion in paediatric Cushing's disease.
AB  - Although paediatric Cushing's disease is rare, it is associated with severe
      morbidity in childhood and presents a major diagnostic and therapeutic challenge
      for the paediatric endocrinologist. Growth failure remains an important feature
      of paediatric Cushing's disease, both at diagnosis and after successful
      treatment. However, the development of specific diagnostic tests and important
      therapeutic advances has contributed significantly to the current management.
      Transsphenoidal pituitary surgery (TSS) is now accepted as first-line therapy for
      both adult and paediatric Cushing's disease, offering the best opportunity for
      cure while preserving normal pituitary function. The cure rate following TSS in
      our centre is currently 62%; therefore, a significant proportion of children
      following TSS will remain uncured. Our favoured second-line therapy is pituitary
      radiotherapy, which is effective, rapid and appears to spare anterior pituitary
      function, with the exception of GH secretion. Growth failure was a symptom at
      diagnosis in 74% of patients; mean height SDS -1.81 (-0.28 to -4.17) compared
      with mean BMI SDS 2.29 (1.72-5.06). Height velocity (HV) was also subnormal;
      range 0.9-3.8 cm/yr. Chronic hypercortisolaemia suppresses linear growth and a
      history of symptoms for >2 years was obtained in 72% of our paediatric patients
      with Cushing's disease. In our series, 9 out of 10 patients did not demonstrate
      catch-up growth 0.64 years after TSS or pituitary radiotherapy and peak serum GH
      level to glucagon/ITT stimulation was 0.5-20.9 mU/l. Assessment of GH secretion
      over a period of 6 to 108 months after cure of paediatric Cushing's disease
      suggests that impaired GH secretion may persist into adult life. Investigation of
      possible GHD is performed in our unit in all post-cure patients who do not show
      optimal catch-up growth. If GH secretion is subnormal, GH replacement is started
      early and continued until final height, when GH secretion is reassessed. In our
      series of 10 patients, 9 received GH therapy, combined in 3 with a GnRH analogue
      to arrest puberty. The results of this treatment were satisfactory with mean
      height deficit compared with target height improving significantly from mean 
      1.72 +/- 1.26 SDS at diagnosis to -0.93 +/- 1.13 SDS (p=0.005) at final height or
      latest assessment, indicating that a favourable final height can be achieved.

PMID- 17003008
TI  - Magnetization transfer imaging of the pituitary gland.
AB  - Magnetization transfer (MT) techniques provide tissue contrast which depends
      mainly on the concentration of macromolecules. The magnetization transfer
      phenomenon is determined by the restricted macromolecular protons and is
      quantified by the magnetization transfer ratio (MTR). Since many macromolecular
      structures are implicated in the secretory activity of the pituitary gland, this
      imaging technique has recently been used for the study of the normal
      adenohypophysis and the pre-operative and post-operative evaluation of pituitary
      adenomas. Significant changes of the MTR with age occur in normal subjects. In
      patients with hyperprolactinemia, the MTR of prolactin-secreting tumors is higher
      and that of the non secreting adenomas is lower compared to the MTR values of the
      normal pituitary gland of age and sex matched controls. In some patients operated
      on for growth hormone adenomas, although classic MR images were negative for
      residual tumor, increased MTR values were highly suggestive of persistence of
      adenoma tissue, in agreement with biochemical findings of persisting secretory
      activity. These data suggest that MT techniques might be an additional useful
      tool in the assessment of pituitary gland disorders.

PMID- 17003009
TI  - The influence of exercise on growth hormone and testosterone in prepubertal and
      early-pubertal boys.
AB  - The purpose of this study was two fold a) to determine the levels of hormonal
      parameters which are related to growth and sexual maturation (T, SHBG, FAI, GH)
      in 66 pre-pubertal and early-pubertal boys (11-13 years old) who systematically
      engage in individual and team sports activities of endurance, strength, speed and
      skill, respectively, and b) to investigate the effect of two different forms of
      exercise namely aerobic (AG) and weight training (WG) on androgen levels in 19
      sedentary pre-pubertal boys. The control groups (CG) consisted of boys of the
      same age who attended only the school physical education programmes. The
      individuals included in the study participated voluntarily after their parents
      had been informed and had given their written consent. Hormonal concentrations
      were determined using radioimmunoassay and immunoradiometric assays. No
      differences were observed among the various athletes' groups as regards Tanner
      stages, height and weight. The mean T and FAI values of the control group did not
      differ from those of the corresponding athletes group. Significant differences
      were observed among the groups regarding BMI, % body fat, T, SHBG, FAI and GH
      (p<0.05). T and FAI values in the WG group were significantly higher than the
      corresponding concentrations: a) in the AG group by 338 and 609%, p<0.05 and b)
      in the control group CG by 91 and 96%, p<0.05, respectively. The hormonal
      differences detected among the various groups of athletes must be attributed as
      much to the type of physical exercise and to developmental factors as to the
      selection criteria used for the different athletic talents. The importance of the
      specificity of training stimulus in the hormonal adaptations of pre-pubertal
      sedentary subjects was demonstrated.

PMID- 17003011
TI  - Laron syndrome. First report from Greece.
AB  - Laron-type dwarfism is an autosomal recessive disorder caused by deletions or
      mutations of the growth hormone receptor gene. It is characterized by high
      circulating levels of growth hormone (GH) and low levels of insulin-like growth
      factor I (IGF-I). Patients are refractory to both endogenous and exogenous GH,
      and present severe growth retardation and obesity. Therapy with recombinant human
      insulin-like growth factor-I (rhIGF-I) accelerates linear growth. We describe a 2
      year old girl with Laron syndrome, who presented with postnatal growth failure
      and hypoglycaemic seizures. Her evaluation disclosed high GH values during a
      glucagon test (peak GH value 170 ng/ml) and very low IGF I value (0.1 ng/ml) with
      no rise following GH administration. The growth velocity improved considerably
      with the administration of IGF I. Molecular analysis showed a heterozygous
      mutation on exon 4 of the GH receptor gene, inherited from the mother, a rather
      puzzling finding considering the clinical findings in mother and infant. This
      case constitutes the first report of Laron syndrome from Greece.

PMID- 17003010
TI  - Transient congenital hypothyroidism due to maternal autoimmune thyroid disease.
AB  - The neonatal screening program for congenital hypothyroidism (CH) in Greece shows
      an overall incidence of the disease of 1:2321. The cases with permanent CH have
      an incidence of 1:2542, whereas the transient forms of CH account for 8.7% of all
      cases diagnosed as CH. Transplacental passage of maternal thyrotropin receptor
      blocking antibodies is a rare cause of transient CH. In our program, a
      retrospective analysis of 508,358 screened newborns revealed 6 infants with
      transient CH caused by maternal thyroid autoimmunity, representing 2.7% of all
      cases of CH. All the newborns with transient CH, due to maternal autoimmune
      thyroid disease, had high serum TSH concentration (ranging from 98 to 689 mU/L),
      whereas serum thyroxine (T4) values were low normal to normal in 3 of them.
      Replacement therapy with L-thyroxine was initiated at a mean age of 6.5 days. The
      newborns with transient CH belonged to 4 families, one of which had 4 and another
      2 children with the same pathology. Thyrotropin-receptor antibodies (TSH-R Abs),
      present at the initial examination in newborns' serum, had disappeared from the
      infants' circulation by the third month of life. One mother carried the Abs for
      at least 8 years during which period she delivered four babies. The diagnosis of
      transient CH should be suspected if the mother has autoimmune thyroid disease, if
      there are siblings with transient CH or if there is no need for an increase in L
      thyroxine dose with advancing age. The diagnosis is very important for genetic
      counseling, early treatment initiation of subsequent offspring and adequate
      control of the mother's thyroid function during subsequent pregnancies so that
      any neurodevelopmental abnormality of the fetus could be avoided.

PMID- 17003013
TI  - Macroprolactinemia in a young man and review of the literature.
AB  - A 21-year old man, complaining of headaches and fatigue, with a negative past
      medical history and a normal clinical examination, underwent a hormonal
      investigation which revealed hyper-prolactinemia and intact pituitary-gonadal
      axis. Drug-induced hyperprolactinemia was excluded. Pituitary magnetic resonance
      imaging indicated a microadenoma in the right part of the gland, with a diameter
      of 1.5mm. No medical treatment was given as the patient had no symptoms relevant
      to prolactin excess. The PEG precipitation test was carried out and showed 7%
      recovery, which was diagnostic of the macroprolactinemia. Relatively few cases of
      macroprolactinemia have been published in the literature, although the condition
      is regarded as a fairly common cause of hyperprolactinemia. Macroprolactinemic
      men represent 10% of published cases.

PMID- 17003012
TI  - Hypoglycaemia secondary to the secretion of pro-insulin like growth factor II by
      a metastatic neuroendocrine tumour with sarcomatous differentiation.
AB  - A patient presented with frequent episodes of spontaneous hypoglycaemia due to a
      disseminated neuroendocrine tumour with sarcomatous differentiation, secreting
      incompletely processed pro-insulin-like growth factor II (pro-IGF-II). Although
      the combination of GH and glucocorticoid therapy initially controlled the
      hypoglycaemia, there was a later escape necessitating frequent re-admissions to
      hospital. The patient deceased two weeks following her latest admission.

PMID- 17003014
TI  - Tracing the origin of the term "gene".

PMID- 17003015
TI  - Pituitary hyperplasia.
AB  - Pituitary hyperplasia is rare, difficult to diagnose and sometimes controversial.
      The hyperplasia could be physiologic which is usually reversible, or pathologic
      which varies in presentation from incidental to tumor like lesion with and
      without hormonal disturbance. Any pituitary cell is capable of undergoing
      hyperplasia in the presence of the right stimuli. In this article we summarize
      the various pathologic and morphologic features of each subtype of pituitary
      hyperplasia, give an account of the molecular, hormonal and cellular basis of
      this condition and outline its clinical significance, differential diagnosis and
      prognosis.

PMID- 17003016
TI  - The treacherous use of thyroxine preparations. Stability of thyroxine
      preparations.

PMID- 17003017
TI  - Relative iron "overload" in offspring of patients with type 2 diabetes mellitus:
      a new component in the conundrum of insulin resistance syndrome?
AB  - There are a few reports suggesting that subtle disturbances of iron metabolism
      are frequently found in patients with type 2 diabetes (DM2), but it is not known
      if these disturbances precede or accompany the diabetic state. We investigated
      the serum iron indices in 41 offspring of DM2 parents (group I) with normal
      glucose tolerance, and in 49 offspring whose parents had no history of DM2 and
      were matched for sex, age, body mass index (BMI), waist to hip ratio (WHR) and
      blood pressure (group II). Serum iron, ferritin, total iron binding capacity
      (TIBC), transferrin saturation, serum triglycerides, cholesterol, Apo-B, high
      density lipoprotein (HDL) and glucose and insulin values during an oral glucose
      tolerance test were measured. Insulin resistance was assessed using the
      homeostasis model assessment (HOMA - Insuline resistence index-IRI). In
      comparison to controls (group II), the offspring of DM2 subjects (group I) had
      higher fasting serum triglycerides (mean +/- SD 2.25+/-2.08 vs. 1.6+/-0.8 mmol/L,
      p<0,05), lower HDL cholesterol (0.96 +/- 0.2 vs. 1.1 +/- 0.2 mmol/L, p<0.001),
      higher total cholesterol (5.5 +/- 1.1 vs. 5.1 +/- 0.8 mmol/L, p < 0.05), higher
      apo-B-lipoprotein (133.2+/-34.3 vs. 125.5+/-30.5 mg/dl, p<0.05), higher LDL-C
      (3.7 +/- 0.8 vs. 3.2 +/- 0.6 mmol/L), higher gamma-GT (28+/-10 vs. 17+/-5.6 iu/L,
      p<0.01) higher insulin in the Area Under the Curve (204.7+/-140.8 v. 153.1 +/-
      63.0 microU/ml, p<0.05) and higher HOMA-IRI (2.84+/-1.39 vs. 1.67+/-0.77,
      p<0.001), higher serum ferritin concentrations (98.3+/-57.7 vs. 62.0+/-41.1
      ng/ml, p<0.01), higher serum iron concentration (20.2+/-6.0 micromol/L vs. 14.5+/
      4.3, p<0.001) and higher transferrin saturation index (31.3+/-8.4 vs. 22.6+/-7.3,
      p<0.0001). By single linear analysis in the offspring of DM2 parents, there was a
      positive correlation of IRI with transferrin saturation (r=0.400, p<0.01),
      fibrinogen (r=0.377, p=0.025) and ferritin concentration (r=0.344, p=0.041), and
      a negative correlation with TIBC (r=-0.477, p < 0.0001), while stepwise multiple
      regression analysis, IRI showed a positive correlation with fibrinogen (b=0.64,
      t=3.746, p<0.001), triglycerides (b=0.37, t=2.619, p<0.01) and ferritin (b=0.20,
      t=1.827, p=0.05). No correlation of IRI, with any of the above parameters was
      seen in the offspring of normal parents. By logistic regression analysis the
      parameters characterizing the offspring of parents with DM2 were IRI (OR 14.9 CI
      2.4-91.0) serum iron (OR 44.2 CI 6.9-281), TIBC (OR 6.1 CI 1.01-37.0 and gamma-GT
      (OR 29.6 CI 5.0-174). In conclusion, the data indicate that the iron load, is
      significantly increased in offspring of DM2 subjects with unaffected glucose
      tolerance. Furthermore, ferritin concentration is related to insulin resistance.
      Hence, the relative iron "overload" in offspring of type 2 diabetics is present
      along with insulin resistance and might worsen the hepatic insulin insensitivity
      already present in these patients.

PMID- 17003018
TI  - The use of recombinant human thyrotropin (Thyrogen) in the diagnosis and
      treatment of thyroid cancer.
AB  - The introduction of human recombinant thyrotropin (rhTSH/Thyrogen) into the
      diagnosis of thyroid cancer has substantially ameliorated the patient's quality
      of life through the avoidance of debilitating hypothyroidism. With the aim of
      updating the use of Thyrogen, we report 7 cases which were treated with Thyrogen
      for diagnostic or therapeutic purposes. All 7 patients were thyroidectomised and
      radioiodine ablated and all had detectable [> 1 ng/ml] basal serum thyroglobulin
      (b-Tg) levels. Thyrogen stimulation resulted in a rise of Tg (s-Tg) in all
      patients. Five patients had negative whole body scanning (WBS) and no clinical or
      radiological signs of disease. Two patients with a b-Tg value of 5 ng/ml and 11
      ng/ml, respectively showed a s-Tg of 17 ng/ml and 84 ng/ml, respectively, whereas
      WBS was negative. Both of these patients received 100 mCi (3700 MBq) 131I. Owo
      patients had a positive Tg and positive WBS with skull, lung and hepatic
      metastases and received 150 131I after preparation with Thyrogen. Six months
      later one of these patients was free of disease and the other will be evaluated
      during the coming months. In conclusion, Thyrogen emerges as a reliable and safe
      agent for the diagnosis of thyroid cancer. Furthermore, it appears that Thyrogen
      could be used in the treatment of metastases as an alternative to thyroid hormone
      withdrawal.

PMID- 17003019
TI  - Stature of early Europeans.
AB  - The ancestors of modern Europeans arrived in Europe at least 40,000 years before
      present. Pre-glacial maximum Upper Palaeolithic males (before 16,000 BC) were
      tall and slim (mean height 179 cm, estimated average body weight 67 kg), while
      the females were comparably small and robust (mean height 158 cm, estimated
      average body weight 54 kg). Late Upper Palaeolithic males (8000-6600 BC) were of
      medium stature and robusticity (mean height 166 cm, estimated average body weight
      62 kg). Stature further decreased to below 165 cm with estimated average body
      weight of 64 kg in Neolithic males of the Linear Band Pottery Culture, and to 150
      cm with estimated average body weight of 49 kg in Neolithic females. The body
      stature of European males remained within the range of 165 to 170 cm up to the
      end of the 19th century.

PMID- 17003020
TI  - Congenital lipoid adrenal hyperplasia caused by a frame-shift mutation in the
      steroidogenic acute regulatory protein gene.
AB  - We present a female patient who, at the age of 35 days, presented with adrenal
      insufficiency with salt loss. Clinical and endocrinological investigation (low to
      normal levels of all adrenal steroids and raised ACTH) and imaging studies
      suggested congenital lipoid adrenal hyperplasia. The diagnosis was confirmed by
      molecular analysis that showed a frame-shift mutation 947/InsA/948 in exon 7 of
      the steroidogenic acute regulatory protein (StAR) gene. The patient is thriving
      under glucocorticoid and mineralocorticoid replacement therapy. She is now 10.5
      years old and has not presented any signs of puberty.

PMID- 17003022
TI  - The Hippocratic spirit.

PMID- 17003021
TI  - Macroprolactinemia. Is treatment necessary?
AB  - A 26-year old symptom-free woman was admitted to our Clinic for evaluation of
      hyperprolactinemia. The patient, who had normal menstrual cycles, was found
      accidentally to have a cystic adnexal mass and was placed on oral contraceptives
      (OC) for 3 months. During the first OC-cycle a bilateral breast nipple discharge
      was noticed and an elevated serum prolactin (PRL) was detected (2.7 nmol/l). The
      OC was discontinued and bromocriptine therapy was started. Serum PRL levels were
      restored and spontaneous menses resumed. The Pituitary magnetic resonance imaging
      (MRI), the anterior pituitary function, assessed by dynamic tests, and the
      thyroid hormone levels were normal. Upon bromocriptine discontinuation, PRL
      levels increased to 13.8 nmol/l. Poly-ethylene-glycol precipitation of the
      patient's serum, in two consecutive measurements, demonstrated the presence of
      macroprolactinemia. Since the patient was asymptomatic, a dopamine agonist was
      not resumed. Macroprolactinemia is characterized by most authors, as a benign
      condition with no clinical implications. However, a number of investigators
      challenge this view, suggesting that in some cases mild symptomatology is present
      possibly requiring therapeutic intervention.

PMID- 17003023
TI  - The influence of serum cortisol levels on growth hormone responsiveness to GH
      releasing hormone plus GH-releasing peptide-6 in patients with hypocortisolism.
AB  - The aim of this study was to evaluate the influence of circulating cortisol
      levels on the somatotroph responsiveness to the most potent stimuli of growth
      hormone (GH) secretion, the GHRH+GHRP-6 test. We studied 12 patients with
      hypocortisolism (10 with Addison's disease and 2 with isolated ACTH deficiency)
      before and after glucocorticoid (GC) replacement therapy and compared them with
      14 healthy subjects. In the 10 patients with Addison's disease, GH responses (GH
      peak, microg/L) to GHRH+GHRP-6 were similar both during GC, (68.2+/-12.8) and off
      GC (60.3+/-14.1) therapy and did not differ from those in controls (61.5+/-6.0).
      In a subgroup of 4 patients with newly diagnosed Addison's disease, GH
      responsiveness to GHRH+GHRP-6 prior to GC replacement (26.4+/-4.1) was
      significantly lower than in the 6 patients with long-standing Addison's disease
      after short-term GC withdrawal (82.9+/-18.2). In the newly diagnosed Addison's
      patients, after one month of GC replacement, mean GH peak value increased to
      40.7+/-11.8. In the 2 patients with isolated ACTH deficiency, GH responses to
      GHRH+GHRP-6 did not differ off and on GC therapy (60.3+/-14.1 and 41.5+/-2.0,
      respectively). Our data suggest that short-term GC deprivation does not have a
      major impact on GH responsiveness to GHRH+GHRP-6. However, in patients with long
      standing hypocortisolism, GH response is blunted but still within normal range (>
      15 microg/L).

PMID- 17003024
TI  - Genetic testing in clinical endocrinology.

PMID- 17003025
TI  - Genetics and hormones in testicular descent.
AB  - Testicular descent is an essential part of normal male sexual development. Any
      anomaly that disrupts normal testicular descent will be clinically evident as
      cryptorchidism. Several factors, such as Hoxa-10, epidermal growth factor (EGF),
      calcitonin gene-related peptide (CGRP), and hormones, especially androgens and
      insulin-like factor 3 (INSL-3), have been suggested as being regulators of
      testicular descent. Testicular descent from the lower pole of the kidney into the
      extra-abdominal scrotal sac is a two-stage process of transabdominal and inguino
      scrotal migration. The transabdominal phase is androgen independent, whereas the
      inguino-scrotal phase depends on androgen action. Disruption of androgen action
      eg. by environmental anti-androgens are suspected as contributing to
      cryptorchidism. Estrogens can down-regulate INSL-3 production and thereby disturb
      testicular descent. Familial occurrence in some cases suggests a possible genetic
      background for cryptorchidism.

PMID- 17003026
TI  - GH deficiency in adults.
AB  - Until the last decade, the diagnosis of GH deficiency (GHD) in adults was only
      considered as a marker of hypothalamo-pituitary disease. GHD in adults is now
      recognized as a specific clinical syndrome associated with a cluster of
      cardiovascular risk factors such as altered body composition with increased body
      fat, insulin resistance, adverse lipid profile, reduced physical performance,
      reduced bone mineral density and impaired quality of life. Several randomized
      placebo controlled trials have now established that GH replacement can reverse
      some of these biological changes and improve the overall health status in GHD
      adults; as a consequence, GH replacement therapy has now been approved in many
      countries in such patients. With the advent of recombinant technology, there is a
      virtually unlimited, safe supply of recombinant human GH. Although GH replacement
      is not administered as commonly as steroid, thyroid and sex hormones in
      hypopituitary patients, a six-month trial of GH replacement with re-evaluation of
      well-being, body composition and lipid profile is currently recommended. However,
      there is marked individual variability in the response to GH replacement, with
      IGF-I being the most sensitive serum marker of GH action. Questions yet remaining
      to be answered relate to the role of GH replacement in cases of partial GHD and
      its use in the elderly population. The safety of long term replacement therapy
      remains an important issue, particularly in relation to the cardio-vascular
      system, the incidence of de novo malignant tumours and the recurrence rate of
      pituitary tumours. In the context of safety, it remains essential to monitor
      patients by means of longitudinal surveillance databases.

PMID- 17003027
TI  - The-2548G/A polymorphism in the human leptin gene promoter region is associated
      with plasma free leptin levels; interaction with adiposity and gender in healthy
      subjects.
AB  - A common -2548G/A promoter variant of the human leptin gene has recently been
      shown to be associated with variations in circulating leptin levels but available
      data are still conflicting. The aim of this study was to explore potential
      associations between the -2548G/A polymorphism and adiposity-related variables,
      plasma total leptin levels, as well as soluble leptin receptor (sOB-R) levels and
      free leptin in a group of healthy Greek subjects. One hundred eighteen
      consecutively enrolled subjects [62 females, 56 males; mean age+/-SD: 17.7+/-1.8
      years; body mass index (BMI) range: 15.4-35.9 kg/m2] were genotyped for the 
      2548G/A polymorphism and their BMI, fat free mass, % fat mass, fasting plasma
      total leptin and sOB-R levels were determined. The ratio leptin/sOB-R was used as
      an index of free leptin. No significant differences in genotype and allele
      frequencies of the -2548G/A polymorphism were detected between normal weight and
      overweight subjects, and no association was found between this polymorphism and
      BMI, fat mass or plasma total leptin levels. However, the -2548G/A polymorphism
      was found to be associated with circulating free leptin levels in a gender
      specific manner. More specifically, compared to carriers of the -2548G allele,
      female subjects with the A/A genotype had higher age and fat mass adjusted mean
      (+/-SE) plasma concentrations of sOB-R (32.9+/-7.2 vs. 25.6+/-3.8 ng/ml, P=0.05),
      and significantly lower (approx. 50%) leptin/sOB-R values (0.74+/-0.25 vs. 1.42+/
      0.13, P=0.02). Furthermore, multiple regression analysis revealed that, after
      adjustment to fat mass, the -2548G/A genotype and gender are significantly
      associated with free leptin index in the entire study sample. Similar regression
      models revealed a significant interaction of gender and genotype when considered
      in addition to fat mass, or fat mass and genotype when considered in addition to
      gender, as predictors of free leptin index. In conclusion, the common -2548G/A
      promoter variant of the human leptin gene is associated with plasma free leptin
      levels through an interaction with adiposity and gender in healthy subjects.

PMID- 17003028
TI  - Effect of restoration of euthyroidism on peripheral blood cells and
      erythropoietin in women with subclinical hypothyroidism.
AB  - BACKGROUND: In overt hypothyroidism (OH) anemia is common, while less frequently
      basophilia has been described. In subclinical hypothyroidism (SCH), however, data
      on the distribution of peripheral blood cells are lacking. Therefore, we
      evaluated the effects of L-T4 replacement therapy on peripheral blood elements in
      female patients with SCH before and after restoration of euthyroidism in a
      randomized, double-blind and placebo-controlled study. PATIENTS AND METHODS:
      Sixty-six women with SCH (TSH 12.9 +/- 8.2 mU/L) were randomly assigned to
      receive L-thyroxine or placebo for 48 weeks. 63 of the 66 women completed the
      study. Peripheral blood cells were measured at baseline and 48 weeks after L
      thyroxine or placebo treatment, respectively. RESULTS: The percentage of
      lymphocytes decreased (p<0.05), whereas percent of monocytes (p<0.05) and
      eosinophiles (p<0.05) increased significantly upon restoration of euthyroidism
      after 48 weeks. Hemoglobin and hematocrit remained unchanged throughout the study
      period. However, erythropoietin levels increased significantly (p<0.01) during L
      T4 treatment. In the placebo group all parameters remained unchanged throughout
      the study. CONCLUSIONS: Overall, we observed subtle alterations of the leuco
      lympho-monocytic distribution of the peripheral blood cells upon restoration of
      euthyroidism in patients with SCH. Hemoglobin and Hematocrit remained unchanged;
      however, the increasing level of erythropoietin during L-T4 treatment suggests an
      already stimulated, yet compensated erythropoietic system in mild thyroid
      failure.

PMID- 17003029
TI  - Cancer in the thyroid is not always thyroid cancer.
AB  - Most clinicians assume that a thyroid mass which appears to be malignant is most
      likely a tumour arising from thyroid cells. We present a case where the thyroid
      malignancy was associated with a degree of systemic clinical and biochemical
      disturbance which suggested alternative diagnoses, and in which fine-needle
      aspiration revealed that the patient had a thyroid lymphoma. Gastric biopsy
      showed that this was a primary gastric diffuse B cell lymphoma. Subsequent
      management provided a number of challenging and overlapping problems, and the
      patient eventually died from this high-grade malignancy. We review the
      prevalence, presentation, diagnosis and management of lymphomas presenting as
      thyroid masses, and underline the problems in management when there is multi
      system disease.

PMID- 17003030
TI  - Sensitivity of the yeast mitochondrial RNA polymerase to +1 and +2 initiating
      nucleotides.
AB  - Despite a simple consensus sequence, there is considerable variation of promoter
      strengths, transcription rates, and the kinetics of initiating nucleotide
      incorporation among the promoters found in the Saccharomyces cerevisiae
      mitochondrial genome. We asked how changes in the initiating (+1 and +2)
      nucleotides, conformation of the promoter DNA template, and mutation of the
      mitochondrial RNA polymerase (mtRNAP) affect the kinetics of nucleotide (NTP)
      utilization. Using a highly purified in vitro mitochondrial transcription system,
      we found that 1) the mtRNAP requires the highest concentrations of the +1 and +2
      initiating NTPs, intermediate concentrations of NTPs at positions 5 to 11, and
      low concentrations of elongating NTPs; 2) the mtRNAP requires a higher
      concentration of the +2 NTP than the +1 NTP for initiation; 3) the kinetics of +2
      NTP utilization are altered by a point mutation in the mtRNAP subunit Mtf1; and
      4) a supercoiled or pre-melted promoter DNA template restores normal +2 NTP
      utilization by the Mtf1 mutant. Based on comparisons to the structural and
      biochemical properties of the bacterial RNAP and the closely related T7 RNAP, we
      propose that initiating nucleotides, particularly the +2 NTP, are required at
      high concentrations to drive mitochondrial promoter opening or to stabilize a
      productive open complex.

PMID- 17003031
TI  - Novel benzene ring biosynthesis from C(3) and C(4) primary metabolites by two
      enzymes.
AB  - The shikimate pathway, including seven enzymatic steps for production of
      chorismate via shikimate from phosphoenolpyruvate and erythrose-4-phosphate, is
      common in various organisms for the biosynthesis of not only aromatic amino acids
      but also most biogenic benzene derivatives. 3-Amino-4-hydroxybenzoic acid (3,4
      AHBA) is a benzene derivative serving as a precursor for several secondary
      metabolites produced by Streptomyces, including grixazone produced by
      Streptomyces griseus. Our study on the biosynthesis pathway of grixazone led to
      identification of the biosynthesis pathway of 3,4-AHBA from two primary
      metabolites. Two genes, griI and griH, within the grixazone biosynthesis gene
      cluster were found to be responsible for the biosynthesis of 3,4-AHBA; the two
      genes conferred the in vivo production of 3,4-AHBA even on Escherichia coli. In
      vitro analysis showed that GriI catalyzed aldol condensation between two primary
      metabolites, l-aspartate-4-semialdehyde and dihydroxyacetone phosphate, to form a
      7-carbon product, 2-amino-4,5-dihydroxy-6-one-heptanoic acid-7-phosphate, which
      was subsequently converted to 3,4-AHBA by GriH. The latter reaction required
      Mn(2+) ion but not any cofactors involved in reduction or oxidation. This pathway
      is independent of the shikimate pathway, representing a novel, simple enzyme
      system responsible for the synthesis of a benzene ring from the C(3) and C(4)
      primary metabolites.

PMID- 17003032
TI  - A novel alpha-helix in the first fibronectin type III repeat of the neural cell
      adhesion molecule is critical for N-glycan polysialylation.
AB  - Polysialic acid is a developmentally regulated, anti-adhesive glycan that is
      added to the neural cell adhesion molecule, NCAM. Polysialylated NCAM is critical
      for brain development and plays roles in synaptic plasticity, axon guidance, and
      cell migration. The first fibronectin type III repeat of NCAM, FN1, is necessary
      for the polysialylation of N-glycans on the adjacent immunoglobulin domain. This
      repeat cannot be replaced by other fibronectin type III repeats. We solved the
      crystal structure of human NCAM FN1 and found that, in addition to a unique
      acidic surface patch, it possesses a novel alpha-helix that links strands 4 and 5
      of its beta-sandwich structure. Replacement of the alpha-helix did not eliminate
      polysialyltransferase recognition, but shifted the addition of polysialic acid
      from the N-glycans modifying the adjacent immunoglobulin domain to O-glycans
      modifying FN1. Other experiments demonstrated that replacement of residues in the
      acidic surface patch alter the polysialylation of both N- and O-glycans in the
      same way, while the alpha-helix is only required for the polysialylation of N
      glycans. Our data are consistent with a model in which the FN1 alpha-helix is
      involved in an Ig5-FN1 interaction that is critical for the correct positioning
      of Ig5 N-glycans for polysialylation.

PMID- 17003033
TI  - Energetics of ligand-induced conformational flexibility in the lactose permease
      of Escherichia coli.
AB  - Isothermal titration calorimetry has been applied to characterize the
      thermodynamics of ligand binding to wild-type lactose permease (LacY) and a
      mutant (C154G) that strongly favors an inward facing conformation. The affinity
      of wild-type or mutant LacY for ligand and the change in free energy (DeltaG)
      upon binding are similar. However, with the wild type, the change in free energy
      upon binding is due primarily to an increase in the entropic free energy
      component (TDeltaS), whereas in marked contrast, an increase in enthalpy (DeltaH)
      is responsible for DeltaG in the mutant. Thus, wild-type LacY behaves as if there
      are multiple ligand-bound conformational states, whereas the mutant is severely
      restricted. The findings also indicate that the structure of the mutant
      represents a conformational intermediate in the overall transport cycle.

PMID- 17003034
TI  - On parallel and antiparallel topology of a homodimeric multidrug transporter.
AB  - The recently suggested antiparallel topology of EmrE has intriguing implications
      for many aspects of the biology of ion-coupled transporters. However, it is at
      odds with biochemical data that demonstrated the same topology for all protomers
      in the intact cell and with extensive cross-linking studies. To examine this
      apparent contradiction we chemically cross-linked dimers with a rigid
      bifunctional maleimide using Cys replacements at positions not permissible by an
      antiparallel topology. A purified cross-linked dimer binds substrate and
      transports it in proteoliposomes with kinetic constants similar to those of the
      non-cross-linked dimer. The cross-linked dimers do not interact with non-cross
      linked dimers as judged from the fact that inactive mutants do not affect their
      activity (negative dominance). The results support the contention that EmrE with
      parallel topology is fully functional. We show that the detergents used in
      crystallization increase the fraction of monomers in solution. We suggest that
      the antiparallel orientation observed is a result of the arrangement of the
      monomers in the crystal. Functionality of EmrE with the suggested antiparallel
      orientation of the monomers remains to be characterized.

PMID- 17003036
TI  - A novel function of ionotropic gamma-aminobutyric acid receptors involving
      alveolar fluid homeostasis.
AB  - Polarized distribution of chloride channels on the plasma membrane of epithelial
      cells is required for fluid transport across the epithelium of fluid-transporting
      organs. Ionotropic gamma-aminobutyric acid receptors are primary ligand-gated
      chloride channels that mediate inhibitory neurotransmission. Traditionally, these
      receptors are not considered to be contributors to fluid transport. Here, we
      report a novel function of gamma-aminobutyric acid receptors involving alveolar
      fluid homeostasis in adult lungs. We demonstrated the expression of functional
      ionotropic gamma-aminobutyric acid receptors on the apical plasma membrane of
      alveolar epithelial type II cells. gamma-Aminobutyric acid significantly
      increased chloride efflux in the isolated type II cells and inhibited apical to
      basolateral chloride transport on type II cell monolayers. Reduction of the gamma
      aminobutyric acid receptor pi subunit using RNA interference abolished the gamma
      aminobutyric acid-mediated chloride transport. In intact rat lungs, gamma
      aminobutyric acid inhibited both basal and beta agonist-stimulated alveolar fluid
      clearance. Thus, we provide molecular and pharmacological evidence that
      ionotropic gamma-aminobutyric acid receptors contribute to fluid transport in the
      lung via luminal secretion of chloride. This finding may have the potential to
      develop clinical approaches for pulmonary diseases involving abnormal fluid
      dynamics.

PMID- 17003035
TI  - IkappaB kinase epsilon interacts with p52 and promotes transactivation via p65.
AB  - The members of the NF-kappaB transcription factor family are key regulators of
      gene expression in the immune response. Different combinations of NF-kappaB
      subunits not only diverge in timing to induce transcription but also recognize
      varying sequences of the NF-kappaB-binding site of their target genes. The p52
      subunit is generated as a result of processing of NF-kappaB2 p100. Here, we
      demonstrate that the non-canonical IkappaB kinase epsilon (IKKepsilon) directly
      interacts with p100. In a transactivation assay, IKKepsilon promoted the ability
      of p52 to transactivate gene expression. This effect was indirect, requiring p65,
      which was shown to be part of the IKKepsilon-p52 complex and to be phosphorylated
      by IKKepsilon. These novel interactions reveal a hitherto unknown function of
      IKKepsilon in the regulation of the alternative NF-kappaB activation pathway
      involving p52 and p65.

PMID- 17003037
TI  - Neuralized-2 regulates a Notch ligand in cooperation with Mind bomb-1.
AB  - Mutations in Drosophila neuralized (Dneur) result in a variety of developmental
      defects that closely resemble those of Notch mutants and other Notch pathway
      mutants. However, mice with disrupted neur1 do not show any aberrant cell fate
      specifications in neurogenesis and somitogenesis. Thus, we speculated that other
      vertebrate neur homolog(s) might compensate for loss of the neur gene. Here, we
      report the paralog of mouse Neur1, named Neuralized-2 (Neur2), which is a
      ubiquitin-protein isopeptide ligase (E3) that interacts with and ubiquitinates
      Delta. Both murine Neur1 and Neur2 have similar degrees of homology to DNeur, and
      neur2 is expressed in patterns similar to those of neur1 in embryos, suggesting
      potential functional redundancy. Interestingly, two distinct classes of E3
      ligases, Mind bomb-1 (Mib1) and Neur2, have cooperative but distinct roles in
      Delta endocytosis to Hrs-positive vesicles, i.e. Mib1 functions in the initial
      step of Delta endocytosis, and Neur2 is required for targeting endocytosed Delta
      to Hrs-positive vesicles. Thus, our study provides a new insight into how
      distinct E3 ligases work together in the endocytic pathways for Notch signaling.

PMID- 17003038
TI  - Regulation of amino acid transporter ATA2 by ubiquitin ligase Nedd4-2.
AB  - We report here that ubiquitin ligase Nedd4-2 regulates amino acid transporter
      ATA2 activity on the cell surface. We first found that a proteasome inhibitor
      MG132 increased the uptake of alpha-(methylamino)isobutyric acid, a model
      substrate for amino acid transport system A, in 3T3-L1 adipocytes as well as the
      preadipocytes. Transient expression of Nedd4-2 in Xenopus oocytes and Chinese
      hamster ovary cells down-regulated the ATA2 transport activity induced by
      injected cRNA and transfected cDNA, respectively. Neither the Nedd4-2 mutant with
      defective catalytic domain nor c-Cbl affected the ATA2 activity significantly.
      RNA-mediated interference of Nedd4-2 increased the ATA2 activity in the cells,
      and this was associated with decreased polyubiquitination of ATA2 on the cell
      surface membrane. Immunofluorescent analysis of Nedd4-2 in the adipocytes stably
      transfected with the enhanced green fluorescent protein (EGFP)-tagged ATA2 showed
      the co-localization of Nedd4-2 and EGFP-ATA2 in the plasma membrane but not in
      the perinuclear ATA2 storage site, supporting the idea that the primary site for
      the ubiquitination of ATA2 is the plasma membrane. These data suggest that ATA2
      on the plasma membrane is subject to polyubiquitination by Nedd4-2 with
      consequent endocytotic sequestration and proteasomal degradation and that this
      process is an important determinant of the density of ATA2 functioning on the
      cell surface.

PMID- 17003039
TI  - Activation mechanism for CRAC current and store-operated Ca2+ entry: calcium
      influx factor and Ca2+-independent phospholipase A2beta-mediated pathway.
AB  - Here we tested the role of calcium influx factor (CIF) and calcium-independent
      phospholipase A2 (iPLA2) in activation of Ca2+ release-activated Ca2+ (CRAC)
      channels and store-operated Ca2+ entry in rat basophilic leukemia (RBL-2H3)
      cells. We demonstrate that 1) endogenous CIF production may be triggered by Ca2+
      release (net loss) as well as by simple buffering of free Ca2+ within the stores,
      2) a specific 82-kDa variant of iPLA2beta and its corresponding activity are
      present in membrane fraction of RBL cells, 3) exogenous CIF (extracted from other
      species) mimics the effects of endogenous CIF and activates iPLA2beta when
      applied to cell homogenates but not intact cells, 4) activation of ICRAC can be
      triggered in resting RBL cells by dialysis with exogenous CIF, 5) molecular or
      functional inhibition of iPLA2beta prevents activation of ICRAC, which could be
      rescued by cell dialysis with a human recombinant iPLA2beta, 6) dependence of
      ICRAC on intracellular pH strictly follows pH dependence of iPLA2beta activity,
      and 7) (S)-BEL, a chiral enantiomer of suicidal substrate specific for iPLA2beta,
      could be effectively used for pharmacological inhibition of ICRAC and store
      operated Ca2+ entry. These findings validate and significantly advance our
      understanding of the CIF-iPLA2-dependent mechanism of activation of ICRAC and
      store-operated Ca2+ entry.

PMID- 17003040
TI  - Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in
      mitochondrial morphology.
AB  - Many muscular and neurological disorders are associated with mitochondrial
      dysfunction and are often accompanied by changes in mitochondrial morphology.
      Mutations in the gene encoding OPA1, a protein required for fusion of
      mitochondria, are associated with hereditary autosomal dominant optic atrophy
      type I. Here we show that mitochondrial fragmentation correlates with processing
      of large isoforms of OPA1 in cybrid cells from a patient with myoclonus epilepsy
      and ragged-red fibers syndrome and in mouse embryonic fibroblasts harboring an
      error-prone mitochondrial mtDNA polymerase gamma. Furthermore, processed OPA1 was
      observed in heart tissue derived from heart-specific TFAM knock-out mice
      suffering from mitochondrial cardiomyopathy and in skeletal muscles from patients
      suffering from mitochondrial myopathies such as myopathy encephalopathy lactic
      acidosis and stroke-like episodes. Dissipation of the mitochondrial membrane
      potential leads to fast induction of proteolytic processing of OPA1 and
      concomitant fragmentation of mitochondria. Recovery of mitochondrial fusion
      depended on protein synthesis and was accompanied by resynthesis of large
      isoforms of OPA1. Fragmentation of mitochondria was prevented by overexpressing
      OPA1. Taken together, our data indicate that proteolytic processing of OPA1 has a
      key role in inducing fragmentation of energetically compromised mitochondria. We
      present the hypothesis that this pathway regulates mitochondrial morphology and
      serves as an early response to prevent fusion of dysfunctional mitochondria with
      the functional mitochondrial network.

PMID- 17003042
TI  - Brain-derived neurotrophic factor activates ERK5 in cortical neurons via a Rap1
      MEKK2 signaling cascade.
AB  - The extracellular signal-regulated kinase 5 (ERK5) is activated in neurons of the
      central nervous system by neurotrophins including brain-derived neurotrophic
      factor (BDNF). Although MEK5 is known to mediate BDNF stimulation of ERK5 in
      central nervous system neurons, other upstream signaling components have not been
      identified. Here, we report that BDNF induces a sustained activation of ERK5 in
      rat cortical neurons and activates Rap1, a small GTPase, as well as MEKK2, a MEK5
      kinase. Our data indicate that activation of Rap1 or MEKK2 is sufficient to
      stimulate ERK5, whereas inhibition of either Rap1 or MEKK2 attenuates BDNF
      activation of ERK5. Furthermore, BDNF stimulation of MEKK2 is regulated by Rap1.
      Our evidence also indicates that Ras and MEKK3, a MEK5 kinase in non-neuronal
      cells, do not play a significant role in BDNF activation of ERK5. This study
      identifies Rap1 and MEKK2 as critical upstream signaling molecules mediating BDNF
      stimulation of ERK5 in central nervous system neurons.

PMID- 17003041
TI  - Bestrophin-1 enables Ca2+-activated Cl- conductance in epithelia.
AB  - Epithelial cells express calcium-activated Cl(-) channels of unknown molecular
      identity. These Cl(-) channels play a central role in diseases such as secretory
      diarrhea, polycystic kidney disease, and cystic fibrosis. The family of
      bestrophins has been suggested to form calcium-activated Cl(-) channels. Here, we
      demonstrate molecular and functional expression of bestrophin-1 (BEST1) in mouse
      and human airways, colon, and kidney. Endogenous calcium-activated whole cell Cl(
      ) currents coincide with endogenous expression of the Vmd2 gene product BEST1 in
      murine and human epithelial cells, whereas calcium-activated Cl(-) currents are
      absent in epithelial tissues lacking BEST1 expression. Blocking expression of
      BEST1 with short interfering RNA or applying an anti-BEST1 antibody to a patch
      pipette suppressed ATP-induced whole cell Cl(-) currents. Calcium-dependent Cl(-)
      currents were activated by ATP in HEK293 cells expressing BEST1. Thus, BEST1 may
      form the Ca2+-activated Cl(-) current, or it may be a component of a Cl(-)
      channel complex in epithelial tissues.

PMID- 17003043
TI  - Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between
      the endoplasmic reticulum and Golgi.
AB  - The recently identified ceramide transfer protein, CERT, is responsible for the
      bulk of ceramide transport from the endoplasmic reticulum (ER) to the Golgi. CERT
      has a C-terminal START domain for ceramide binding and an N-terminal pleck-strin
      homology domain that binds phosphatidylinositol 4-phosphate suggesting that
      phosphatidylinositol (PI) 4-kinases are involved in the regulation of CERT
      mediated ceramide transport. In the present study fluorescent analogues were used
      to follow the ER to Golgi transport of ceramide to determine which of the four
      mammalian PI 4-kinases are involved in this process. Overexpression of pleckstrin
      homology domains that bind phosphatidylinositol 4-phosphate strongly inhibited
      the transport of C5-BODIPY-ceramide to the Golgi. A newly identified PI 3-kinase
      inhibitor, PIK93 that selectively inhibits the type III PI 4-kinase beta enzyme,
      and small interfering RNA-mediated down-regulation of the individual PI 4-kinase
      enzymes, revealed that PI 4-kinase beta has a dominant role in ceramide transport
      between the ER and Golgi. Accordingly, inhibition of PI 4-kinase III beta either
      by wortmannin or PIK93 inhibited the conversion of [3H]serine-labeled endogenous
      ceramide to sphingomyelin. Therefore, PI 4-kinase beta is a key enzyme in the
      control of spingomyelin synthesis by controlling the flow of ceramide from the ER
      to the Golgi compartment.

PMID- 17003044
TI  - The RAC binding domain/IRSp53-MIM homology domain of IRSp53 induces RAC-dependent
      membrane deformation.
AB  - The concave surface of the crescent-shaped Bin-amphiphysin-Rvs (BAR) domain is
      postulated to bind to the cell membrane to induce membrane deformation of a
      specific curvature. The Rac binding (RCB) domain/IRSp53-MIM homology domain (IMD)
      has a dimeric structure that is similar to the structure of the BAR domain;
      however, the RCB domain/IMD has a "zeppelin-shaped" dimer. Interestingly, the RCB
      domain/IMD of IRSp53 possesses Rac binding, membrane binding, and actin filament
      binding abilities. Here we report that the RCB domain/IMD of IRSp53 induces
      membrane deformation independent of the actin filaments in a Rac-dependent
      manner. In contrast to the BAR domain, the RCB domain/IMD did not cause long
      tubulation of the artificial liposomes; however, the Rac binding domain caused
      the formation of small buds on the liposomal surface. When expressed in cells,
      the Rac binding domain induced outward protrusion of the plasma membrane in a
      direction opposite to that induced by the BAR domain. Mapping of the amino acids
      responsible for membrane deformation suggests that the convex surface of the Rac
      binding domain binds to the membrane in a Rac-dependent manner, which may explain
      the mechanism of the membrane deformation induced by the RCB domain/IMD.

PMID- 17003045
TI  - Regulation of the ring finger E3 ligase Siah2 by p38 MAPK.
AB  - The RING finger ubiquitin ligase Siah2 controls the stability of various
      substrates involved in stress and hypoxia responses, including the PHD3, which
      controls the stability of HIF-1alpha. In the present study we determined the role
      of Siah2 phosphorylation in the regulation of its activity toward PHD3. We show
      that Siah2 is subject to phosphorylation by p38 MAPK, which increases Siah2
      mediated degradation of PHD3. Consistent with these findings, MKK3/MKK6 double
      deficient cells, which cannot activate p38 kinases, exhibit impaired Siah2
      dependent degradation of PHD3. Phosphopeptide mapping identified T24 and S29 as
      the primary phospho-acceptor sites. Phospho-mutant forms of Siah2 (S29A or
      T24A/S29A) exhibit impaired degradation of PHD3, particularly after hypoxia.
      Conversely, a phospho-mimic form of Siah2 (T24E/S29D) exhibits stronger
      degradation of PHD3, compared with wild type Siah2. Whereas phospho-mutant Siah2
      exhibits weaker association with PHD3, phospho-mimic Siah2 associates as well as
      wild type and is localized within the perinuclear region, suggesting that
      phosphorylation of Siah2 affects its subcellular localization and, consequently,
      the degree of its association with PHD3. In all, our findings reveal the
      phosphorylation of Siah2 by p38 and the implications of such phosphorylation for
      Siah2 activity toward PHD3.

PMID- 17003046
TI  - Incremental cost-effectiveness of exercise echocardiography vs. SPECT imaging for
      the evaluation of stable chest pain.
AB  - AIMS: Technological advances in cardiac imaging have led to dramatic increases in
      test utilization and consumption of a growing proportion of cardiovascular
      healthcare costs. The opportunity costs of strategies favouring exercise
      echocardiography or SPECT imaging have been incompletely evaluated. METHODS AND
      RESULTS: We examined prognosis and cost-effectiveness of exercise
      echocardiography (n = 4884) vs. SPECT (n = 4637) imaging in stable, intermediate
      risk, chest pain patients. Ischaemia extent was defined as the number of vascular
      territories with echocardiographic wall motion or SPECT perfusion abnormalities.
      Cox proportional hazard models were employed to assess time to cardiac death or
      myocardial infarction (MI). Total cardiovascular costs were summed (discounted
      and inflation-corrected) throughout follow-up. A cost-effectiveness ratio <
      Dollars 50,000 per life year saved (LYS) was considered favourable for economic
      efficiency. The risk-adjusted 3-year death or MI rates classified by extent of
      ischaemia were similar, ranging from 2.3 to 8.0% for echocardiography and from
      3.5 to 11.0% for SPECT (model chi2 = 216; P < 0.0001; interaction P = 0.24). Cost
      effectiveness ratios for echocardiography were < Dollars 20,000/LYS when the
      annual risk of death or MI was < 2%. However, when yearly cardiac event rate were
      > 2%, cost-effectiveness ratios for echocardiography vs. SPECT were in the range
      of Dollars 66,686-Dollars 419,522/LYS. For patients with established coronary
      disease (i.e. > or = 2% annual event risk), SPECT ischaemia was associated with
      earlier and greater utilization of coronary revascularization (P < 0.0001)
      resulting in an incremental cost-effectiveness ratio of Dollars 32,381/LYS.
      CONCLUSION: Health care policies aimed at allocating limited resources can be
      effectively guided by applying clinical and economic outcomes evidence. A
      strategy aimed at cost-effective testing would support using echocardiography in
      low-risk patients with suspected coronary disease, whereas those higher risk
      patients benefit from referral to SPECT imaging.

PMID- 17003047
TI  - Selecting optimal non-invasive cardiac imaging stress test in intermediate-risk
      patients using cost effectiveness analysis.

PMID- 17003048
TI  - The functional reserve of collaterals supplying long-term chronic total coronary
      occlusions in patients without prior myocardial infarction.
AB  - AIMS: Chronic total coronary occlusions (CTOs) with angiographically well
      developed collaterals may be considered to provide sufficient blood supply to the
      occluded segment, and the indication for revascularization may be questioned.
      Therefore, the collateral function and functional reserve in patients with a CTO
      without a prior Q-wave myocardial infarction (MI) were assessed. METHODS AND
      RESULTS: Invasive assessment of collateral function was done during successful
      percutaneous coronary intervention in 107 patients with a CTO and no prior Q-wave
      MI. Intracoronary Doppler flow velocity and pressure recordings were obtained
      distal to the occlusion before the first balloon inflation and collateral
      function indexes calculated. In 62 patients, additional pharmacological stress
      testing was done by intravenous adenosine (140 microg/kg/min) to assess the
      collateral flow reserve. Patients with normal and impaired regional dysfunction
      were compared. Collateral function was similar in patients with and without
      regional left ventricular (LV) dysfunction. In both groups, 78% collaterals
      provided a collateral pressure index at baseline > 0.3, sufficient to prevent
      ischaemia during a balloon occlusion, with a minimum of 0.2 in those with
      preserved LV function. A Doppler-derived function index showed a wider variation
      due to the high prevalence of microvascular dysfunction in CTOs. Only 7% of
      patients had an increase in collateral flow reserve > 2.0 during pharmacological
      stress, whereas coronary steal occurred in one-third independent of regional LV
      function. CONCLUSION: A limited increase in collateral flow and the high
      prevalence of coronary steal during stress underscore the functional limitation
      of collaterals in CTOs without prior Q-wave MI. Even presumably 'well
      collateralized' CTOs may benefit from a revascularization.

PMID- 17003049
TI  - Residence close to high traffic and prevalence of coronary heart disease.
AB  - AIMS: Long-term exposure to urban air pollution may accelerate atherogenesis and
      increase cardiopulmonary mortality. We aim to examine the relationship between
      the long-term residential exposure to traffic and prevalence of coronary heart
      disease (CHD). METHODS AND RESULTS: We used baseline data from the German Heinz
      Nixdorf RECALL study, a population-based, prospective cohort study. For 3399
      participants from two cities, we assessed the long-term personal traffic exposure
      and background air pollution, comparing residents living within 150 m of major
      roads with those living further away. The principal outcome variable was
      clinically manifest CHD. We evaluated the association with multivariable logistic
      regression, controlling for background air pollution and individual level risk
      factors. Of 3399 participants, 242 (7.1%) had CHD. The crude odds ratio (OR) for
      prevalence of CHD at high traffic exposure was significantly elevated (1.62,
      95%CI 1.12-2.34) and rose to 1.85 (95%CI 1.21-2.84) after adjusting for
      cardiovascular risk factors and background air pollution. Subgroup analysis
      showed stronger effects for men (OR 2.33, 95%CI 1.44-3.78), participants younger
      than 60 years (OR 2.67, 95%CI 1.24-5.74) and never-smokers (OR 2.72, 95%CI 1.40
      5.29). CONCLUSION: This study provides epidemiological evidence that the long
      term exposure to traffic-related emissions may be an important risk factor for
      CHD.

PMID- 17003050
TI  - Identifying functional gene sets from hierarchically clustered expression data:
      map of abiotic stress regulated genes in Arabidopsis thaliana.
AB  - We present MultiGO, a web-enabled tool for the identification of biologically
      relevant gene sets from hierarchically clustered gene expression trees
      (http://ekhidna.biocenter.helsinki.fi/poxo/multigo). High-throughput gene
      expression measuring techniques, such as microarrays, are nowadays often used to
      monitor the expression of thousands of genes. Since these experiments can produce
      overwhelming amounts of data, computational methods that assist the data analysis
      and interpretation are essential. MultiGO is a tool that automatically extracts
      the biological information for multiple clusters and determines their biological
      relevance, and hence facilitates the interpretation of the data. Since the entire
      expression tree is analysed, MultiGO is guaranteed to report all clusters that
      share a common enriched biological function, as defined by Gene Ontology
      annotations. The tool also identifies a plausible cluster set, which represents
      the key biological functions affected by the experiment. The performance is
      demonstrated by analysing drought-, cold- and abscisic acid-related expression
      data sets from Arabidopsis thaliana. The analysis not only identified known
      biological functions, but also brought into focus the less established
      connections to defense-related gene clusters. Thus, in comparison to analyses of
      manually selected gene lists, the systematic analysis of every cluster can reveal
      unexpected biological phenomena and produce much more comprehensive biological
      insights to the experiment of interest.

PMID- 17003051
TI  - Crystal structures of oligonucleotides including the integrase processing site of
      the Moloney murine leukemia virus.
AB  - In the first step of retroviral integration, integrase cleaves the linear viral
      DNA within its long terminal repeat (LTR) immediately 3' to the CA dinucleotide
      step, resulting in a reactive 3' OH on one strand and a 5' two base overhang on
      the complementary strand. In order to investigate the structural properties of
      the 3' end processing site within the Moloney murine leukemia virus (MMLV) LTR
      d(TCTTTCATT), a host-guest crystallographic method was employed to determine the
      structures of four self-complementary 16 bp oligonucleotides including LTR
      sequences (underlined), d(TTTCATTGCAATGAAA), d(CTTTCATTAATGAAAG),
      d(TCTTTCATATGAAAGA) and d(CACAATGATCATTGTG), the guests, complexed with the N
      terminal fragment of MMLV reverse transcriptase, the host. The structures of the
      LTR-containing oligonucleotides were compared to those of non-LTR
      oligonucleotides crystallized in the same lattice. Properties unique to the CA
      dinucleotide step within the LTR sequence, independent of its position from the
      end of the duplex, include a positive roll angle and negative slide value. This
      propensity for the CA dinucleotide step within the MMLV LTR sequence to adopt
      only positive roll angles is likely influenced by the more rigid, invariable 3'
      and 5' flanking TT dinucleotide steps and may be important for specific
      recognition and/or cleavage by the MMLV integrase.

PMID- 17003052
TI  - Helicase binding to DnaI exposes a cryptic DNA-binding site during helicase
      loading in Bacillus subtilis.
AB  - The Bacillus subtilis DnaI, DnaB and DnaD proteins load the replicative ring
      helicase DnaC onto DNA during priming of DNA replication. Here we show that DnaI
      consists of a C-terminal domain (Cd) with ATPase and DNA-binding activities and
      an N-terminal domain (Nd) that interacts with the replicative ring helicase. A
      Zn2+-binding module mediates the interaction with the helicase and C67, C70 and
      H84 are involved in the coordination of the Zn2+. DnaI binds ATP and exhibits
      ATPase activity that is not stimulated by ssDNA, because the DNA-binding site on
      Cd is masked by Nd. The ATPase activity resides on the Cd domain and when
      detached from the Nd domain, it becomes sensitive to stimulation by ssDNA because
      its cryptic DNA-binding site is exposed. Therefore, Nd acts as a molecular
      'switch' regulating access to the ssDNA binding site on Cd, in response to
      binding of the helicase. DnaI is sufficient to load the replicative helicase from
      a complex with six DnaI molecules, so there is no requirement for a dual helicase
      loader system.

PMID- 17003053
TI  - The proteins encoded by the pogo-like Lemi1 element bind the TIRs and subterminal
      repeated motifs of the Arabidopsis Emigrant MITE: consequences for the
      transposition mechanism of MITEs.
AB  - MITEs (miniature inverted-repeated transposable elements) are a particular class
      of defective DNA transposons usually present within genomes as high copy number
      populations of highly homogeneous elements. Although an active MITE, the mPing
      element, has recently been characterized in rice, the transposition mechanism of
      MITEs remains unknown. It has been proposed that transposases of related
      transposons could mobilize MITEs in trans. Moreover, it has also been proposed
      that the presence of conserved terminal inverted-repeated (TIR) sequences could
      be the only requirement of MITEs for mobilization, allowing divergent or
      unrelated elements to be mobilized by a particular transposase. We present here
      evidence for a recent mobility of the Arabidopsis Emigrant MITE and we report on
      the capacity of the proteins encoded by the related Lemi1 transposon, a pogo
      related element, to specifically bind Emigrant elements. This suggests that Lemi1
      could mobilize Emigrant elements and makes the Lemi1/Emigrant couple an ideal
      system to study the transposition mechanism of MITEs. Our results show that Lemi1
      proteins bind Emigrant TIRs but also bind cooperatively to subterminal repeated
      motifs. The requirement of internal sequences for the formation of proper
      DNA/protein structure could affect the capacity of divergent MITEs to be
      mobilized by distantly related transposases.

PMID- 17003054
TI  - BP1 is a negative modulator of definitive erythropoiesis.
AB  - Beta protein 1 (BP1), a human homeotic transcription factor, is expressed during
      hematopoeisis in the erythroid lineage. To determine the in vivo role of BP1 in
      erythropoiesis, we have undertaken two complementary approaches using enforced
      BP1 expression in both transgenic mice and embryonic stem (ES) cells. Despite
      repeated attempts, only one adult transgenic BP1 founder mouse among 121 mice was
      obtained. This mouse presumably survived due to transgene mosaicism because the
      transgene could not be transmitted. This mouse expressed BP1 and displayed
      splenomegaly, extramedullary erythropoiesis and severe amyloidosis A in the
      kidney, a phenotype compatible with thalassemia. Consistently, the presence of
      BP1 transgene in fetuses was associated with paleness and lethality. In ES cells,
      BP1 expression in primary differentiation appeared to antagonize adult beta
      globin expression. In secondary differentiation, BP1 expression reduced
      significantly beta-globin gene expression in both primitive and definitive
      erythroid cells, whereas it impaired only the definitive erythroid cell
      differentiation. These studies showed that BP1 can negatively modulate adult beta
      globin gene expression and definitive erythroid cell differentiation, and suggest
      that BP1 could play a role in thalassemia.

PMID- 17003055
TI  - Sequence determinants of breakpoint location during HIV-1 intersubtype
      recombination.
AB  - Retroviral recombination results from strand switching, during reverse
      transcription, between the two copies of genomic RNA present in the virus. We
      analysed recombination in part of the envelope gene, between HIV-1 subtype A and
      D strains. After a single infection cycle, breakpoints clustered in regions
      corresponding to the constant portions of Env. With some exceptions, a similar
      distribution was observed after multiple infection cycles, and among recombinant
      sequences in the HIV Sequence Database. We compared the experimental data with
      computer simulations made using a program that only allows recombination to occur
      whenever an identical base is present in the aligned parental RNAs. Experimental
      recombination was more frequent than expected on the basis of simulated
      recombination when, in a region spanning 40 nt from the 5' border of a
      breakpoint, no more than two discordant bases between the parental RNAs were
      present. When these requirements were not fulfilled, breakpoints were distributed
      randomly along the RNA, closer to the distribution predicted by computer
      simulation. A significant preference for recombination was also observed for
      regions containing homopolymeric stretches. These results define, for the first
      time, local sequence determinants for recombination between divergent HIV-1
      isolates.

PMID- 17003056
TI  - Human RECQ5beta helicase promotes strand exchange on synthetic DNA structures
      resembling a stalled replication fork.
AB  - The role of the human RECQ5beta helicase in the maintenance of genomic stability
      remains elusive. Here we show that RECQ5beta promotes strand exchange between
      arms of synthetic forked DNA structures resembling a stalled replication fork in
      a reaction dependent on ATP hydrolysis. BLM and WRN can also promote strand
      exchange on these structures. However, in the presence of human replication
      protein A (hRPA), the action of these RecQ-type helicases is strongly biased
      towards unwinding of the parental duplex, an effect not seen with RECQ5beta. A
      domain within the non-conserved portion of RECQ5beta is identified as being
      important for its ability to unwind the lagging-strand arm and to promote strand
      exchange on hRPA-coated forked structures. We also show that RECQ5beta associates
      with DNA replication factories in S phase nuclei and persists at the sites of
      stalled replication forks after exposure of cells to UV irradiation. Moreover,
      RECQ5beta is found to physically interact with the polymerase processivity factor
      proliferating cell nuclear antigen in vitro and in vivo. Collectively, these
      findings suggest that RECQ5beta may promote regression of stalled replication
      forks to facilitate the bypass of replication-blocking lesions by template
      switching. Loss of such activity could explain the elevated level of mitotic
      crossovers observed in RECQ5beta-deficient cells.

PMID- 17003057
TI  - Evolution of variants of yeast site-specific recombinase Flp that utilize native
      genomic sequences as recombination target sites.
AB  - As a tool in directed genome manipulations, site-specific recombination is a
      double-edged sword. Exquisite specificity, while highly desirable, makes it
      imperative that the target site be first inserted at the desired genomic locale
      before it can be manipulated. We describe a combination of computational and
      experimental strategies, based on the tyrosine recombinase Flp and its target
      site FRT, to overcome this impediment. We document the systematic evolution of
      Flp variants that can utilize, in a bacterial assay, two sites from the human
      interleukin 10 gene, IL10, as recombination substrates. Recombination competence
      on an end target site is acquired via chimeric sites containing mixed sequences
      from FRT and the genomic locus. This is the first time that a tyrosine site
      specific recombinase has been coaxed successfully to perform DNA exchange within
      naturally occurring sequences derived from a foreign genomic context. We
      demonstrate the ability of an Flp variant to mediate integration of a reporter
      cassette in Escherichia coli via recombination at one of the IL10-derived sites.

PMID- 17003058
TI  - Norwood procedure for hypoplastic left heart syndrome: BT shunt or RV-PA conduit?
AB  - BACKGROUND: The Norwood procedure is the first stage palliative procedure for
      hypoplastic left heart syndrome (HLHS). Traditionally the pulmonary circulation
      has been supplied via a modified Blalock Taussig (BT) shunt but a recent
      modification, adopted in some UK centres, substitutes a conduit between right
      ventricle and pulmonary arteries (RV-PA conduit). It is argued that this will
      result in a more favourable balance between pulmonary and systemic circulations.
      AIM: To compare the early postoperative haemodynamic profile between patients
      undergoing a BT shunt or an RV-PA conduit. METHODS: Retrospective review in a
      tertiary referral PICU of 51 children with HLHS undergoing the Norwood procedure
      with either a BT shunt (Group 1; n = 23) or an RV-PA conduit (Group 2; n = 28).
      Data items were extracted at 10 set time points in the initial 96 h,
      postoperatively. RESULTS: Diastolic BP was significantly lower in Group 1
      (p<0.001) with a trend towards a higher systolic BP and no difference in mean BP.
      No between-group differences were found in markers of pulmonary blood flow (PaO2,
      PaCO2, PaO2/FiO2 ratio), or in markers of systemic blood flow (blood lactate,
      oxygen extraction ratio), or in estimated ratio of pulmonary:systemic blood flow
      (Qp:Qs). Despite lower diastolic blood pressure in Group 1 renal and hepatic
      function did not differ over five post-operative days between groups.
      CONCLUSIONS: With the exception of a higher diastolic blood pressure in the RV-PA
      conduit group, we found no difference in the early haemodynamic profile between
      patients undergoing an RV-PA conduit or a BT shunt.

PMID- 17003059
TI  - Emergence of CTX-M-12 extended-spectrum beta-lactamase-producing Escherichia coli
      in Korea.
AB  - OBJECTIVES: To characterize CTX-M-12 extended-spectrum beta-lactamase (ESBL)
      produced by clinical Escherichia coli isolates and to investigate its genetic
      environment. METHODS: Antimicrobial susceptibilities were determined by disc
      diffusion and agar dilution methods, and the double-disc synergy test was carried
      out. Detection of genes encoding class A beta-lactamases was performed by PCR
      amplification, and the genetic environments of the bla(CTX-M-12) genes were
      investigated by PCR and sequencing of the regions surrounding the genes. Kinetic
      parameters were determined from purified CTX-M-12. RESULTS: Sequence data for the
      CTX-M-1 cluster from three clinical E. coli isolates indicated the presence of
      CTX-M-12. An ISEcp1 insertion sequence was located 49 bp upstream of bla(CTX-M
      12) in all three E. coli isolates. CTX-M-12 had a more potent hydrolytic activity
      against cefotaxime than against ceftazidime and was encoded on a self
      transferable approximately 18 kbp plasmid. CONCLUSIONS: This work shows that CTX
      M-12, which confers high-level resistance to cefotaxime but not to ceftazidime,
      has emerged in Korea. The bla(CTX-M-12) gene was associated with an upstream
      ISEcp1 insertion sequence.

PMID- 17003060
TI  - Bactericidal activity and target preference of a piperazinyl-cross-linked
      ciprofloxacin dimer with Staphylococcus aureus and Escherichia coli.
AB  - BACKGROUND: Previous work showed that piperazinyl-cross-linked ciprofloxacin
      dimer exhibits good bacteriostatic activity with Streptococcus pneumoniae and
      Staphylococcus aureus; lethal activity was not measured. Subsequently, the dimer
      failed to kill Mycobacterium smegmatis but blocked growth. Whether the compound
      is lethal with non-mycobacterial species is not known. METHODS: Bacteriostatic
      and bactericidal activities were measured with wild-type cells and topoisomerase
      mutants of S. aureus and Escherichia coli for ciprofloxacin and a dimer of
      ciprofloxacin. Spontaneous resistance mutants were selected with S. aureus for
      both compounds, followed by target identification by nucleotide sequence
      determination of the quinolone-resistance-determining-region of gyrA (gyrase) and
      parC (topoisomerase IV). RESULTS: The dimer was lethal, in some cases exhibiting
      more activity than ciprofloxacin (particularly with wild-type cells and a parC
      mutant of S. aureus). Dimerization affected target preference with S. aureus but
      not with E. coli. Resistance mutations in either gyrA or parC of S. aureus raised
      the MIC of the dimer, but only a parC mutation raised the MIC of ciprofloxacin.
      With S. aureus, the dimer selected spontaneous resistant gyrA mutants, whereas
      ciprofloxacin selected a parC mutant. With E. coli, a gyrA, but not a parC,
      mutation raised the MIC of both compounds. CONCLUSION: The dimer readily killed
      S. aureus and E. coli, representative gram-positive and gram-negative bacteria.
      In both cases the preferred target was DNA gyrase. The switch in target
      preference may be responsible for the greater lethality of the dimer seen with S.
      aureus.

PMID- 17003061
TI  - Pharmacokinetic and pharmacodynamic assessment of co-amoxiclav in the treatment
      of melioidosis.
AB  - OBJECTIVES: We conducted a prospective pharmacokinetic study of oral co-amoxiclav
      in patients with melioidosis to determine the optimal dosage and dosing interval
      in this potentially fatal infection. PATIENTS AND METHODS: Serial plasma
      concentrations were measured after administration of two 1 g tablets of Augmentin
      (1750 mg of amoxicillin and 250 mg of clavulanate) to 14 adult patients with
      melioidosis. Monte Carlo simulation was used to predict the concentration of each
      drug following multiple doses of co-amoxiclav at different dosages and dose
      intervals. The proportion of the dose-interval above MIC (T > MIC) was calculated
      from 10,000 simulated subject plasma concentration profiles together with
      chequerboard MIC data from 46 clinical isolates and four reference strains of
      Burkholderia pseudomallei. RESULTS: The median (range) observed maximum plasma
      concentrations of amoxicillin and clavulanate were 11.5 (3.3-40.2) mg/L and 5.1
      (0.8-12.1) mg/L, respectively. The median (range) elimination half-lives were 94
      (73-215) and 89 (57-140) min, respectively. Simulation indicated that co
      amoxiclav 1750/250 mg given at 4, 6, 8 or 12 hourly dosing intervals would be
      associated with a T > MIC of < or = 50% in 0.7%, 2.8%, 8.6% and 33.2% of
      patients, respectively. Corresponding proportions for T > MIC of > or = 90% were
      95.8%, 78.6%, 50.2% and 10.8%, respectively. CONCLUSIONS: The dosing interval for
      co-amoxiclav (750/250 mg) in melioidosis should not be greater than 6 h.

PMID- 17003063
TI  - Antibiotic resistance--action to promote new technologies: report of an EU
      Intergovernmental Conference held in Birmingham, UK, 12-13 December 2005.
AB  - The increase in microorganisms that have developed resistance to currently
      available antimicrobial agents has become a major cause for concern worldwide.
      These organisms are widespread in hospitals but also occur increasingly in the
      community. Some of these strains are multiresistant and the agents available to
      treat infections caused by them are few and dwindling. Over recent years there
      have been a number of responses by national, international and professional
      bodies to this situation, many aimed at curbing this unprecedented growth in
      resistance, but there is an increasing recognition that a major problem in the
      management of infections caused by such organisms is the paucity of new drugs,
      vaccines and diagnostic aids. A conference, organized by the Specialist Advisory
      Committee on Antimicrobial Resistance (SACAR) on behalf of the UK Department of
      Health and sponsored by the BSAC, was held in Birmingham in December 2005 with
      the aim of addressing these problems. Conference attendees included those from
      academia, industry, funding agencies, healthcare management, the European
      Medicines Agency (EMEA), the European Centre for Disease Prevention and Control
      (ECDC), European Directorates and representatives of EU governments. Following a
      number of keynote presentations which identified major issues, there were a
      series of workshops which addressed specific questions and produced a number of
      recommendations. These recommendations were discussed by all delegates. The lack
      of new anti-infectives and the reasons for this were discussed in some detail.
      Major pharmaceutical companies no longer find this area as financially rewarding
      as other therapeutic areas while smaller biotechnology companies, who are seen as
      more innovative, are hampered by a lack of funding. In spite of a few marked
      successes, the use of vaccines has had minimal impact in the field of bacterial
      infections, and progress in this field also suffers from a lack of funding.
      Diagnostics could aid in the better use of antibacterials but need greater
      acceptance in the healthcare system, which does not generally appreciate their
      cost-efficacy. The major recommendations were as follows: (i) Increased efforts
      are needed to reduce the spread of resistant strains both in the environment and
      in hospitals--these include improved hygiene and decreased use of some
      antimicrobials. (ii) Surveillance of resistance is a key factor and improved
      technology (e.g. IT systems) is needed to improve the potential for surveillance
      data to inform clinical practice. (iii) Rapid, sensitive and specific diagnostics
      are urgently needed and the issue of reimbursement needs to be addressed. (iv)
      More accurate estimates of the cost-efficacy of using anti-infectives and
      diagnostics are urgently needed. (v) Vaccine technology is available but is
      underused for the prevention of bacterial infections, particularly those caused
      by organisms resistant to antimicrobials. (vi) Incentives are required to
      encourage large pharmaceutical companies to partner small biotechnology
      companies, which are more innovative and have the potential to deliver the new
      drugs, diagnostics and vaccines. Modifications to the international regulatory
      requirements for drug licensing could have a major impact on the time and thus
      the costs of developing new agents.

PMID- 17003065
TI  - Bioinformatics-driven, rational engineering of protein thermostability.
AB  - A longstanding goal in protein engineering is to identify specific sequence
      changes that endow proteins with desired functional properties. As opposed to
      traditional rational and random protein engineering techniques, we have employed
      a bioinformatic approach to identify specific sequence changes that influence key
      functional properties of a protein within a defined superfamily. Specifically, we
      have used the Bayesian sequence-based algorithms PROBE and Classifier to identify
      a strand-turn-strand motif that contributes to thermophilicity among members of
      the serine protease subtilase superfamily. By replacing a 16 amino acid sequence
      in the mesophilic subtilisin E (from Bacillus subtilis) with a bioinformatics
      generated thermophilic model sequence, the melting temperature of subtilisin E
      was increased by 13 degrees C. While wild-type subtilisin E was inactive at 90
      degrees C, the mutant retained a substantial fraction of its function, with ca.
      one-third of the activity that it has at 45 degrees C.

PMID- 17003064
TI  - What is the rationale for hydrocortisone treatment in children with infection
      related adrenal insufficiency and septic shock?
AB  - Recent studies show that children who die from fulminant meningococcaemia have
      very low cortisol:adrenocorticotrophic hormone (ACTH) ratios within the first 8 h
      of presentation to emergency facilities compared with survivors. This observation
      supports the possibility that adrenal insufficiency may contribute to rapid
      cardiovascular collapse in these children. In recent years, the use of
      hydrocortisone treatment has become increasingly popular in the care of adult and
      paediatric patients with septic shock. In this review, the classical adrenal
      insufficiency literature is presented and the existing rationale for using
      titrated hydrocortisone treatment (2-50 mg/kg/day) to reverse catecholamine
      resistant shock in children who have absolute adrenal insufficiency (defined by
      peak cortisol level <18 microg/dl after ACTH challenge) or pituitary,
      hypothalamic or adrenal axis insufficiency is provided. In addition, the concept
      of relative adrenal insufficiency (basal cortisol >18 microg/dl but a peak
      response to ACTH <9 microg/dl) is reviewed. Although there is a good rationale
      supporting the use of 7 days of low-dose hydrocortisone treatment (about 5
      mg/kg/day) in adults with this condition and catecholamine resistant septic
      shock, the paediatric literature suggests that it is prudent to conduct more
      studies before recommending this approach in children.

PMID- 17003066
TI  - Anaesthetic management of a child with fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia Ossificans Progressiva (FOP) is a rare inherited disease in which
      progressive ossification of striated muscles leads to severe disability and
      respiratory impairment early in life and there are associated characteristic
      congenital skeletal malformations. Although this condition may prove demanding
      for the anaesthetist, few reports are available regarding anaesthesia in
      paediatric patients. We review the clinical features of the disease relevant to
      anaesthesia and describe the perioperative care of an 18-month-old boy with FOP
      who underwent endoscopic third-ventriculostomy for hydrocephalus associated with
      a brainstem mass. We emphasize the importance of an appropriate anaesthetic
      management of these patients, as inadequate care may lead to exacerbation of the
      disease with permanent sequelae.

PMID- 17003067
TI  - Cross-modal reorganization and speech perception in cochlear implant users.
AB  - Recent work suggests that once the auditory cortex of deaf persons has been
      reorganized by cross-modal plasticity, it can no longer respond to signals from a
      cochlear implant (CI) installed subsequently. To further examine this issue, we
      compared the evoked potentials involved in the processing of visual stimuli
      between CI users and hearing controls. The stimuli were concentric circles
      replaced by a different overlapping shape, inducing a shape transformation, known
      to activate the ventral visual pathway in human adults. All CI users had their
      device implanted for >1 year, but obtained different levels of auditory
      performance following training to establish language comprehension. Seven of the
      13 patients showed good capacities for speech recognition with the CI (good
      performers) while the six others demonstrated poor speech recognition abilities
      (poor performers). The evoked potentials of all patients showed larger
      amplitudes, with different distributions of scalp activations between the two
      groups. The poor performers exhibited broader, anteriorly distributed, high P2
      amplitudes over the cortex whereas the good performers showed significantly
      higher P2 amplitudes over visual occipital areas. These results suggest the
      existence of a profound cross-modal reorganization in the poor performers and an
      intramodal reorganization in the good performers. We interpret these data on the
      basis of enhanced audiovisual coupling as the key to a long-term functional
      improvement in speech discrimination in CI users.

PMID- 17003068
TI  - Time-frequency analysis reveals decreased high-frequency oscillations in writer's
      cramp.
AB  - High-frequency oscillations (HFO) have been suggested to reflect the activity of
      thalamocortical and/or intracortical neurons bursting at high frequencies. These
      circuits seem to be involved in pathophysiological mechanisms of focal dystonia.
      In healthy subjects, we characterized the spectrotemporal properties of HFO
      patterns evoked by dominant-hand median-nerve stimulation, using
      magnetoencephalography coupled with time-frequency analysis. Then, we
      investigated HFO in patients with writer's cramp and found that HFO patterns are
      strongly decreased in power and disorganized in time. This supports the
      assumption that abnormal HFOs reflect pathophysiological mechanisms occurring in
      focal dystonia, possibly resulting from a dysfunction of somatosensory
      processing.

PMID- 17003069
TI  - Progranulin gene mutations associated with frontotemporal dementia and
      progressive non-fluent aphasia.
AB  - Frontotemporal lobar degeneration (FTLD) refers to a focal, non-Alzheimer form of
      cerebral degeneration that encompasses the distinct clinical syndromes of
      frontotemporal dementia (FTD), progressive non-fluent aphasia (PNFA) and semantic
      dementia. Some patients show tau-based pathological changes and in familial cases
      mutations have been identified in the microtubule-associated protein tau gene
      (MAPT) on chromosome 17q21. However, many cases are tau-negative, showing instead
      ubiquitin-immunoreactive (UBQ-ir) neuronal cytoplasmic inclusions and neurites,
      and in some familial cases UBQ-ir neuronal intranuclear inclusions of a lentiform
      appearance. Very recently, mutations have been identified in familial cases in
      the progranulin (PGRN) gene, also on chromosome 17q21. Clinical, pathological and
      molecular diversity within FTLD highlights the importance of careful examination
      of clinical-pathological-genetic relationships. This paper reports, for the first
      time, a clinico-pathological investigation of two FTLD families with PGRN
      mutations, and compares the clinical characteristics with those of patients
      studied in the department with MAPT mutations. The clinical profile associated
      with PGRN mutations constituted, in some patients, a prototypical picture of FTD
      and in others one of PNFA, both profiles occurring within the same family.
      Patients with PGRN mutations exhibited phonological deficits, whereas in patients
      with MAPT mutations language abnormalities, when present in addition to the
      prominent behavioural disorder, take the form of semantic disturbance. The
      findings provide compelling evidence for the link between FTD and PNFA, while
      raising the possibility of identifiable clinical differences between FTLD
      patients with MAPT and PGRN mutations.

PMID- 17003070
TI  - Increased IL-23p19 expression in multiple sclerosis lesions and its induction in
      microglia.
AB  - IL-12 has long been considered important in the pathogenesis of multiple
      sclerosis. However, evidence from recent studies strongly supports the critical
      role of IL-12-related proinflammatory cytokine IL-23, but not IL-12, in the
      development of experimental autoimmune encephalomyelitis (EAE), an animal model
      of this disease. The role of IL-23 in the CNS immunity of multiple sclerosis
      patients has not been elucidated; nor is it known whether human microglia produce
      this cytokine. In this study we investigated the expression of IL-23p19 and p40,
      with its key subunit p19 as the focus, in histologically characterized CNS
      specimens from multiple sclerosis and control cases using in situ hybridization
      and immunohistochemistry. A significant increase in mRNA expression and protein
      production of both subunits of IL-23 was found in lesion tissues compared with
      non-lesion tissues. Double staining showed that activated macrophages/microglia
      were an important source of IL-23p19 in active and chronic active multiple
      sclerosis lesions. We also detected IL-23p19 expression in mature dendritic cells
      which were preferentially located in the perivascular cuff of active lesions. The
      finding that human microglia produce IL-23 was further confirmed by the inducible
      production of IL-23p19 and p40 in cultured human microglia in vitro upon
      different Toll-like receptor stimulations. Taken together, these findings on the
      expression of IL-23p19 in multiple sclerosis lesions may lead to a better
      understanding of the events culminating in human multiple sclerosis.

PMID- 17003071
TI  - Selective affection of hippocampal CA-1 neurons in patients with transient global
      amnesia without long-term sequelae.
AB  - The aetiology, pathomechanisms and anatomical correlates of transient global
      amnesia (TGA) still remain obscure. Recently, focal MR-signal diffusion-weighted
      imaging (DWI) changes in the hippocampus have been described in patients with
      TGA, but the exact localization, long term outcome and pathophysiological nature
      of these lesions still remain unknown. The topography and time course of
      hippocampal DWI lesions in 41 TGA patients was studied using serial 3 T high
      resolution MR-imaging and correlated to clinical and neuropsychometric results.
      Of these, 29 patients showed 36 DWI lesions with corresponding T(2) lesions in
      the hippocampus within a time window of 48 h after onset. Almost all lesions
      (94%; 34/36) were selectively found in the CA-1 sector (Sommer sector) of the
      hippocampal cornu ammonis. Most DWI lesions (8/10) were already detectable in the
      peri-acute phase <6 h after onset of symptoms. A follow-up study 4-6 months after
      the episode did not show evidence for residual structural sequelae of these
      lesions (n = 20/20). A venous MR angiography of the intracranial dural sinus
      showed an asymmetric venous drainage in 21/24 (88%) patients. In 11/16 (69%)
      patients with unilateral lesions, the asymmetry corresponded to the side of the
      DWI lesion. Significant episodic verbal memory deficits in the acute phase (n =
      14/18) were associated with lesions of the dominant hemisphere while impairment
      of visuospatial memory was associated with lesions of the non-dominant
      hemisphere. Persistent neuropsychological sequelae were not detected 4-6 months
      after the episode (n = 16). This is the first prospective study combining high
      resolution imaging and neuropsychometry analysing the detailed functional anatomy
      and outcome of hippocampal DWI/T(2) lesions in TGA supporting the view the TGA
      being a benign transient disorder. The TGA can be considered a model for a focal
      transient perturbation of memory circuits in the temporo-mesial region.

PMID- 17003073
TI  - Strategies for dealing with incomplete information in the modeling of molecular
      interaction networks.
AB  - Modelers of molecular interaction networks encounter the paradoxical situation
      that while large amounts of data are available, these are often insufficient for
      the formulation and analysis of mathematical models describing the network
      dynamics. In particular, information on the reaction mechanisms and numerical
      values of kinetic parameters are usually not available for all but a few well
      studied model systems. In this article we review two strategies that have been
      proposed for dealing with incomplete information in the study of molecular
      interaction networks: parameter sensitivity analysis and model simplification.
      These strategies are based on the biologically justified intuition that essential
      properties of the system dynamics are robust against moderate changes in the
      value of kinetic parameters or even in the rate laws describing the interactions.
      Although advanced measurement techniques can be expected to relieve the problem
      of incomplete information to some extent, the strategies discussed in this
      article will retain their interest as tools providing an initial characterization
      of essential properties of the network dynamics.

PMID- 17003072
TI  - The adult form of Niemann-Pick disease type C.
AB  - Niemann-Pick disease type C (NPC) is a fatal neurovisceral lipid storage disease
      of autosomal inheritance resulting from mutations in either the NPC1 (95% of
      families) or NPC2 gene. The encoded proteins appear to be involved in
      lysosomal/late endosomal transport of cholesterol, glycolipids and other
      molecules but their exact function is still unknown. The clinical spectrum of the
      disease ranges from a neonatal rapidly fatal disorder to an adult-onset chronic
      neurodegenerative disease. Based upon a comprehensive study of 13 unrelated adult
      patients diagnosed in France over the past 20 years as well as the analysis of
      the 55 other cases published since 1969, we have attempted to delineate the major
      clinical, radiological, biochemical and genotypic characteristics of adult NPC.
      Overall, mean age at onset (+/-SD) of neuropsychiatric symptoms was 25 +/- 9.7
      years. The diagnosis of NPC was established after a mean delay of 6.2 +/- 6.4
      years and the mean age at death (calculated from 20 cases) was 38 +/- 10.2 years.
      Major clinical features included cerebellar ataxia (76%), vertical supranuclear
      ophthalmoplegia (VSO, 75%), dysarthria, (63%), cognitive troubles (61%), movement
      disorders (58%), splenomegaly (54%), psychiatric disorders (45%) and dysphagia
      (37%). Less frequent signs were epilepsy and cataplexy. During the course of the
      disease, clinical features could be subdivided into (i) visceral signs
      (hepatomegaly or splenomegaly), (ii) cortical signs (psychiatric cognitive
      disorders and epilepsy); and (iii) deep brain signs (VSO, ataxia, movement
      disorders, dysarthria, dysphagia, cataplexy) which exhibited different evolution
      patterns. Asymptomatic and non-evolutive visceral signs were often noticed since
      early childhood (38.5% of our patients), followed by mild cortical signs in
      childhood (learning difficulties) and early adulthood (62% of cases among which
      38% were psychiatric disorders). Deep brain signs were observed in 96% of
      patients and were usually responsible for death. In general, there was a good
      correlation between clinical signs and the localization of brain atrophy on MRI.
      The 'variant' biochemical phenotype characterized by mild abnormalities of the
      cellular trafficking of endocytosed cholesterol was over-represented in the adult
      form of NPC and seemed associated with less frequent splenomegaly in childhood
      and lesser psychiatric signs. Involvement of the NPC1 gene was shown in 33
      families and of the NPC2 gene in one. Improving the knowledge of the disease
      among psychiatrists and neurologists appears essential since emerging treatments
      should be more efficient at the visceral or cognitive/psychiatric stages of the
      disease, before the occurrence of widespread deep brain neurological lesions.

PMID- 17003074
TI  - The WWWH of remote homolog detection: the state of the art.
AB  - The detection of remote homolog pairs of proteins using computational methods is
      a pivotal problem in structural bioinformatics, aiming to compute protein folds
      on the basis of information in the database of known structures. In the last 25
      years, several methods have been developed to tackle this problem, based on
      different approaches including sequence-sequence alignments and/or structure
      comparison. In this article, we will briefly discuss When, Why, Where and How
      (WWWH) to perform remote homology search, reviewing some of the most widely
      adopted computational approaches. The specific aim is highlighting the basic
      criteria implemented by different research groups and commenting on the status of
      the art as well as on still-open questions.

PMID- 17003075
TI  - Health benefits in 2006: premium increases moderate, enrollment in consumer
      directed health plans remains modest.
AB  - Based on a survey of 2,122 randomly selected public and private employers, this
      paper reports on the state of employer-sponsored health insurance in spring 2006,
      including recent changes. Premiums increased 7.7 percent from spring 2005 to
      spring 2006 and have risen 68 percent since 2001. About 4 percent of workers are
      enrolled in high-deductible health plans with savings options. The percentage of
      workers covered by their own employer did not statistically change from 2005 to
      2006.

PMID- 17003076
TI  - The 'pitcher pot' ileal neobladder: early experiences.
AB  - OBJECTIVE: To analyse initial results of newly designed ileal neobladder-a
      modification of Studer neobladder METHODS: Twenty-four patients with urinary
      bladder cancer underwent radical cystoprostatectomy from February 2005 to March
      2006. Twenty-one of them had urinary diversion using ileal neobladder in
      spherical configuration with ileal neourethra (giving the shape of an inverted
      Indian earthenware container called a 'pitcher pot') to circumvent the problem of
      short mesentery and construct a low-pressure spherical ileal neobladder. RESULTS:
      Early post-operative complications occurred in 42% of patients. Late
      complications occurred in 23% of patients. Most of these complications were
      minor, mainly as a result of wound infection, urine leak or urinary tract
      infections and were managed conservatively. No early post-operative mortality was
      observed. Daytime continence was achieved in 100% of patients who completed the 1
      year follow-up. Night-time continence was variable as it depended on timed
      voiding--75% of patients achieved nocturnal continence by 1 year. The functional
      neobladder capacity was 426 ml. The mean post-operative residual volume was 36
      ml. Three patients required cystoscopic mucus evacuation and catheterization.
      None of them required clean intermittent catheterization. No significant
      metabolic disturbance occurred in any patient. CONCLUSIONS: Length of mesentery
      remains one of the factors in deciding the segment of intestine to be taken for
      neobladder. Ileal neourethra gives about 2-3 cm extra length to perform
      tensionless anastomosis, which is a key factor in the smooth recovery after such
      major surgery and also maintains optimum urodynamic features of neobladder.

PMID- 17003077
TI  - From customer satisfaction survey to corrective actions in laboratory services in
      a university hospital.
AB  - OBJECTIVE: To find out the satisfaction of clinical units with laboratory
      services in a university hospital, to point out the most important problems and
      defects in services, to carry out corrective actions, and thereafter to identify
      the possible changes in satisfaction. SETTING: and STUDY PARTICIPANTS: Senior
      physicians and nurses-in-charge of the clinical units at Oulu University
      Hospital, Finland. DESIGN: Customer satisfaction survey using a questionnaire was
      carried out in 2001, indicating the essential aspects of laboratory services.
      Customer-specific problems were clarified, corrective actions were performed, and
      the survey was repeated in 2004. RESULTS: In 2001, the highest dissatisfaction
      rates were recorded for computerized test requesting and reporting, turnaround
      times of tests, and the schedule of phlebotomy rounds. The old laboratory
      information system was not amenable to major improvements, and it was renewed in
      2004-05. Several clinical units perceived turnaround times to be long, because
      the tests were ordered as routine despite emergency needs. Instructions about
      stat requesting were given to these units. However, no changes were evident in
      the satisfaction level in the 2004 survey. Following negotiations with the
      clinics, phlebotomy rounds were re-scheduled. This resulted in a distinct
      increase in satisfaction in 2004. CONCLUSIONS: Satisfaction survey is a screening
      tool that identifies topics of dissatisfaction. Without further clarifications,
      it is not possible to find out the specific problems of customers and to
      undertake targeted corrective actions. Customer-specific corrections are rarely
      seen as improvements in overall satisfaction rates.

PMID- 17003078
TI  - Dissociation of stimulus relevance and saliency factors during shifts of
      visuospatial attention.
AB  - The control of visuospatial attention entails multiple processes, including both
      voluntary (endogenous) factors and stimulus-driven (exogenous) factors. Exogenous
      processes can be triggered by visual targets presented at a previously unattended
      location, thus capturing attention in a stimulus-driven manner. However, little
      is known about the relative role of stimulus salience and behavioral relevance
      for this type of spatial reorienting. Here, we directly assessed how salience and
      relevance affect activation of the frontoparietal attentional system, using
      either low-salience but task-relevant target stimuli or salient but task
      irrelevant flickering checkerboards. We compared event-related functional
      magnetic resonance imaging responses for stimuli presented at the unattended
      versus attended side (invalid minus valid trials), separately for the 2
      categories of visual stimuli. We found that task-relevant invalid targets
      activated the frontoparietal attentional network, demonstrating that this system
      engages when target stimuli are presented at an unattended location, even when
      these have a low perceptual salience. Conversely, the presentation of high
      salience checkerboards in one hemifield while endogenous attention was engaged
      elsewhere did not activate the attentional network. These findings indicate that
      task relevance is critical for stimulus-driven engagement of the attentional
      network when attentional resources are endogenously allocated somewhere else.

PMID- 17003079
TI  - Novel algorithm for transcriptome analysis.
AB  - A growing body of evidence implicates the oocyte as a key regulator of ovarian
      folliculogenesis and early embryonic development. We have screened bovine cDNA
      microarrays (containing expressed sequence tags representing >15,000 unique
      genes) with Cy3- and Cy5-labeled cDNA derived from bovine oocyte samples
      collected at two different stages of meiotic maturation (germinal vesicle vs.
      metaphase II; n = 3 samples per group). Here, we present a novel data analysis
      approach that uses all available information from above experiments to obtain and
      index the transcriptome of bovine oocytes and changes in transcriptome
      composition in response to meiotic maturation. Signal intensities (Fg) for all
      housekeeping genes were omitted prior to analysis. A local threshold for gene
      expression was computed as background intensity (Bg) plus 2 times the standard
      deviation of background and foreground signals. Within each array, data were
      normalized by the LOWESS procedure. Subsequently, a two-stage mixed model was
      fitted to remove systematic variations. In the first stage, the response was the
      LOWESS normalized Fg with treatment as a fixed effect. In stage 2, the residuals
      from stage 1 were analyzed in a gene-specific model that included treatment group
      and spots nested within patch and array. A test for the difference between least
      squares means for the treatment effect was performed. A false discovery rate
      (FDR) adjustment on the p values for the difference was carried out. This novel
      algorithm was compared with approaches that ignore the FDR and the threshold
      described herein and stark differences obtained.

PMID- 17003080
TI  - Relief of acute pain in chronic idiopathic gastroparesis with intravenous
      phentolamine.
AB  - OBJECTIVE: To report a case in which complete relief of pain associated with
      gastroparesis, with promotion of gastric emptying, was achieved with
      administration of phentolamine. CASE SUMMARY: A 37-year-old opiate-tolerant
      female with a history of recurrent abdominal pain, gastroparesis, cyclic vomiting
      syndrome, and migraine headaches was admitted to the emergency department (ED)
      with severe acute abdominal pain, nausea, and vomiting. The patient had been
      previously implanted with a permanent gastric electrical stimulator and she was
      adherent to her prokinetic, antiemetic, analgesic, and migraine prophylactic
      medications. Pain relief was achieved rapidly and completely in the ED with
      sympatholysis by administration of intravenous phentolamine 0.5 mg/kg over 60
      minutes, with continuous cardiac monitoring. At a 2 month follow-up visit, the
      patient reported chronic pain relief, and a decrease in opiate doses was
      maintained by oral administration of clonidine 0.1 mg twice daily. DISCUSSION:
      Gastroparesis represents a difficult treatment challenge because management of
      gastric dysmotility and the accompanying severe abdominal pain is often mutually
      exacerbating and ineffective. Sympatholysis by intravenous phentolamine provided
      profound and immediate relief of acute gastroparesis-related abdominal pain in
      our patient. The mechanism of phentolamine is believed to be receptor blockade at
      alpha-adrenergic receptors and, therefore, inhibition of the peripheral
      sensitizing effects of circulating norepinephrine. Although action at a
      peripheral nerve level is presumed, modulation of alpha-adrenoreceptors receptors
      is also possible at the dorsal root ganglion or at other central nervous system
      sites. CONCLUSIONS: The dramatic relief of acute pain in gastroparesis by
      phentolamine observed in this case would warrant investigation of a larger,
      controlled case series. Patients who respond to intravenous sympatholysis may
      likewise be candidates for longer term sympathetic modulation with oral
      sympatholytics.

PMID- 17003081
TI  - Renin-angiotensin system mediators and Raynaud's phenomenon.
AB  - OBJECTIVE: To review the use of angiotensin-converting enzyme (ACE) inhibitors
      and angiotensin II receptor blockers (ARBs) in the treatment of Raynaud's
      phenomenon (RP). DATA SOURCES: Biomedical literature was accessed through July
      2006 via PubMed, the Iowa Drug Information System (IDIS), and Cumulative Index to
      Nursing and Allied Health Literature (CINAHL) Plus. PubMed database terms
      included Raynaud's disease, angiotensin-converting enzyme inhibitors, and
      angiotensin II type 1 receptor blockers [pharmacological action]; IDIS terms
      included hypotensive agents-ace inhib 24080200, raynaud's syndrome 443.0, and
      hypotensive agents-angioten II 24080400; and CINAHL Plus terms included Raynaud's
      disease, angiotensin-converting enzyme inhibitors, losartan, and irbesartan.
      STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in English
      that reported both subjective and objective outcomes of efficacy were reviewed.
      DATA SYNTHESIS: Several small, short-term studies have evaluated captopril,
      enalapril, and losartan in the treatment of RP. The studies of ACE inhibitors
      have found conflicting results in their ability to improve digit blood flow and
      reduce both frequency and severity of RP attacks. Two studies have focused on the
      use of losartan for RP treatment, with both finding a statistically significant
      reduction in attacks and one showing improvement in symptoms of RP in comparison
      with the commonly utilized calcium-channel blocker, nifedipine. Most of the
      studies were short term (< or =12 wk) and included a limited number of patients
      (<60). CONCLUSIONS: ACE inhibitors and ARBs may provide some minor benefits in
      the relief of RP, although no definite evidence exists to suggest that they are
      superior to traditionally used treatments such as calcium-channel blockers.
      Larger, randomized controlled trials of longer duration are needed to compare the
      effectiveness of ACE inhibitors and ARBs with conventional treatment.

PMID- 17003082
TI  - Efficacy and safety of rosuvastatin every other day compared with once daily in
      patients with hypercholesterolemia.
AB  - BACKGROUND: Although most patients with hypercholesterolemia require life-long
      therapy with statins, these drugs are underused due to high costs. Every-other
      day therapy could be one strategy to resolve this problem. OBJECTIVE: To compare
      the efficacy and safety of rosuvastatin 10 mg administered every other day versus
      once daily. METHODS: An 8 week, randomized, open-label, parallel trial was
      conducted at the outpatient department of Phramongkutklao Hospital in Bangkok,
      Thailand. Eighty patients with primary hypercholesterolemia were equally
      randomized to receive rosuvastatin 10 mg once daily or every other day; 76
      patients completed the study. Laboratory data were assessed at baseline and at
      the end of the study. RESULTS: Low-density lipoprotein cholesterol (LDL-C) levels
      were reduced by 48% and 39% in the once-daily and every-other-day groups,
      respectively (p = 0.011). The percentage of patients who achieved LDL-C goals
      according to National Cholesterol Education Program-Adult Treatment Panel III
      guidelines was not significantly different between the once-daily (85%) and every
      other-day (70%) groups (p = 0.180). In addition, both regimens were well
      tolerated, with no patient developing an elevation of more than 3 times baseline
      levels of aspartate aminotransferase or alanine aminotransferase or 10 times that
      of creatine kinase. As expected, the monthly cost per percent LDL-C reduction of
      the once-daily (0.72 dollars) regimen was about 38% higher than that of the every
      other-day (0.44 dollars) regimen. CONCLUSIONS: Every-other-day dosing of
      rosuvastatin may be an alternative regimen for cost savings, without a major
      decrease in therapeutic benefit or increase in adverse events, in patients with
      hypercholesterolemia. The number of patients achieving their LDL-C goal using the
      every-other-day regimen is comparable with the number using the once-daily
      regimen, especially in the low-risk patient category.

PMID- 17003083
TI  - Prevalence of subclinical thyroid dysfunction and its relation to socioeconomic
      deprivation in the elderly: a community-based cross-sectional survey.
AB  - CONTEXT: Population-based screening has been advocated for subclinical thyroid
      dysfunction in the elderly because the disorder is perceived to be common, and
      health benefits may be accrued by detection and treatment. OBJECTIVE: The
      objective of the study was to determine the prevalence of subclinical thyroid
      dysfunction and unidentified overt thyroid dysfunction in an elderly population.
      DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey of a community sample
      of participants aged 65 yr and older registered with 20 family practices in the
      United Kingdom. EXCLUSIONS: Exclusions included current therapy for thyroid
      disease, thyroid surgery, or treatment within 12 months. OUTCOME MEASURE: Tests
      of thyroid function (TSH concentration and free T4 concentration in all, with
      measurement of free T3 in those with low TSH) were conducted. EXPLANATORY
      VARIABLES: These included all current medical diagnoses and drug therapies, age,
      gender, and socioeconomic deprivation (Index of Multiple Deprivation, 2004).
      ANALYSIS: Standardized prevalence rates were analyzed. Logistic regression
      modeling was used to determine factors associated with the presence of
      subclinical thyroid dysfunction. RESULTS: A total of 5960 attended for screening.
      Using biochemical definitions, 94.2% [95% confidence interval (CI) 93.8-94.6%]
      were euthyroid. Unidentified overt hyper- and hypothyroidism were uncommon (0.3,
      0.4%, respectively). Subclinical hyperthyroidism and hypothyroidism were
      identified with similar frequency (2.1%, 95% CI 1.8-2.3%; 2.9%, 95% CI 2.6-3.1%,
      respectively). Subclinical thyroid dysfunction was more common in females (P <
      0.001) and with increasing age (P < 0.001). After allowing for comorbidities,
      concurrent drug therapies, age, and gender, an association between subclinical
      hyperthyroidism and a composite measure of socioeconomic deprivation remained.
      CONCLUSIONS: Undiagnosed overt thyroid dysfunction is uncommon. The prevalence of
      subclinical thyroid dysfunction is 5%. We have, for the first time, identified an
      independent association between the prevalence of subclinical thyroid dysfunction
      and deprivation that cannot be explained solely by the greater burden of chronic
      disease and/or consequent drug therapies in the deprived population.

PMID- 17003084
TI  - Induction of surfactant protein A expression by cortisol facilitates
      prostaglandin synthesis in human chorionic trophoblasts.
AB  - CONTEXT: Surfactant protein A (SP-A) may be an important link between the
      maturation of fetal organs and the initiation of parturition. However, the local
      expression of SP-A and the effect of SP-A on prostaglandin synthesis in human
      fetal membranes have not been resolved. OBJECTIVE: Our objective was to examine
      SP-A expression and the effect of SP-A on prostaglandin synthesis in human fetal
      membranes. DESIGN: SP-A expression was examined with immunohistochemistry and
      PCR. The effect of SP-A on prostaglandin synthesis was investigated in cultured
      human chorionic trophoblasts. PATIENTS: Patients were normal-term pregnant women
      undergoing elective cesarean sections. RESULTS: Both SP-A protein and mRNA were
      present in amnion epithelial cells, fibroblasts, and chorionic trophoblasts.
      Cortisol (10(-7) and 10(-6) M, 24 h) induced SP-A expression in cultured
      chorionic trophoblasts, which could be blocked by the glucocorticoid receptor
      antagonist RU486. Treatment of chorionic trophoblasts with SP-A (10-100
      microg/ml, 24 h) caused a dose-dependent increase of prostaglandin E2 release and
      an induction of cyclooxygenase type 2 but not cytosolic phospholipase A2 and
      microsomal prostaglandin E synthase expression. CONCLUSIONS: SP-A can be
      synthesized locally in human fetal membranes, which can be induced by
      glucocorticoids. SP-A appeared to induce prostaglandin E2 synthesis in chorionic
      trophoblasts via induction of cyclooxygenase type 2 expression.

PMID- 17003085
TI  - Characterizing discrete subsets of polycystic ovary syndrome as defined by the
      Rotterdam criteria: the impact of weight on phenotype and metabolic features.
AB  - CONTEXT: The Rotterdam criteria for polycystic ovary syndrome (PCOS) defines
      discrete subgroups whose phenotypes are not yet clear. OBJECTIVE: The phenotypic
      characteristics of women in the PCOS subgroups defined by the Rotterdam criteria
      were compared. DESIGN: The study was observational. SETTING: Subjects were
      studied in an outpatient setting in Boston and Reykjavik. PATIENTS: Four
      subgroups of subjects with PCOS defined by 1) irregular menses (IM),
      hyperandrogenism (HA), and polycystic ovary morphology (PCOM, n = 298); 2) IM/HA
      (n = 7); 3) HA/PCOM (n = 77); and 4) IM/PCOM (n = 36) and a group of controls (n
      = 64), aged 18-45 yr, were examined. INTERVENTION: Subjects underwent a physical
      exam; fasting blood samples for androgens, gonadotropins, and metabolic
      parameters; and a transvaginal ultrasound. MAIN OUTCOME MEASURES: The phenotype
      was compared between groups. RESULTS: Ninety-seven percent of women with IM/HA
      had PCOM. Therefore, the groups with and without PCOM were combined. The Ferriman
      Gallwey score and androgen levels were highest in the hyperandrogenic groups
      (IM/HA and HA/PCOM), whereas ovarian volume was higher in all PCOS subgroups
      compared with controls, as expected based on the definitions of the PCOS
      subgroups. Body mass index and insulin levels were highest in the IM/HA subgroup.
      CONCLUSIONS: Subjects with PCOS defined by IM/HA are the most severely affected
      women on the basis of androgen levels, ovarian volumes, and insulin levels. Their
      higher body mass index partially accounts for the increased insulin levels,
      suggesting that weight gain exacerbates the symptoms of PCOS.

PMID- 17003086
TI  - Increased visfatin messenger ribonucleic acid and protein levels in adipose
      tissue and adipocytes in women with polycystic ovary syndrome: parallel increase
      in plasma visfatin.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease
      linked with insulin resistance (IR) and obesity. Recent studies have shown that
      plasma levels of the insulin-mimetic adipokine visfatin increase with obesity.
      Currently, no data exist on the relative expression of visfatin in either plasma
      or adipose tissue of PCOS women. OBJECTIVES: We investigated the mRNA expression
      of visfatin from sc and omental (om) adipose tissue and sc adipocytes in women
      with PCOS compared with matched normal women, as well as visfatin protein in
      adipose tissue; plasma visfatin was also assessed. DESIGN: Real-time RT-PCR and
      Western blotting were used to assess the relative mRNA and protein expression of
      visfatin. Biochemical measurements were performed. RESULTS: There was significant
      up-regulation of visfatin mRNA in both sc (P < 0.05) and om (P < 0.05) adipose
      tissue of PCOS women, when compared with normal controls; these findings were
      also reflected in isolated sc adipocytes (PCOS > controls; P < 0.05). In addition
      to elevated plasma visfatin levels in women with PCOS (mean +/- sd, 30.2 +/- 10.4
      vs. 11.2 +/- 6.2 ng/ml; P < 0.01) when compared with normal controls, visfatin
      protein levels were significantly greater in both sc and om adipose tissue of
      PCOS women (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: The precise reason
      for the up-regulation of visfatin seen in women with PCOS, a proinflammatory
      state, is unknown. Additional studies are needed to clarify the potential role of
      visfatin in the pathophysiology of PCOS.

PMID- 17003087
TI  - Exon 3-deleted/full-length growth hormone receptor polymorphism genotype
      frequencies in Spanish short small-for-gestational-age (SGA) children and
      adolescents (n = 247) and in an adult control population (n = 289) show increased
      fl/fl in short SGA.
AB  - CONTEXT: A polymorphism in the human GH receptor gene (d3/fl-GHR) resulting in
      genomic deletion of exon 3 has been associated with the degree of height increase
      in response to GH therapy. OBJECTIVE: The objective of the study was to evaluate
      the frequencies of d3/fl-GHR polymorphism genotypes in control and short small
      for-gestational-age (SGA) populations. DESIGN: An adult control population with
      heights normally distributed (ACPNH) between -2 and +2 sd score (SDS) and a short
      non-GH-deficient SGA child population were selected. SETTING: Thirty Spanish
      hospitals participated in the selection of the short non-GH-deficient SGA
      children in the setting of a controlled, randomized trial, and one of these
      hospitals selected the ACPNH. CONTROLS AND PATIENTS: Two hundred eighty-nine
      adult subjects of both sexes constituted the ACPNH and 247 children and
      adolescents of both sexes the short SGA patients. MAIN OUTCOME MEASURES: Heights
      and weights were recorded in the ACPNH, and auxologic and biochemical data were
      recorded at each hospital for the SGA patients; d3/fl-GHR genotypes were
      determined and data analyzed in a single hospital. RESULTS: In short SGA
      patients, d3/fl-GHR genotype frequencies were significantly different from those
      in ACPNH, with a higher frequency of fl/fl genotype (P < 0.0001). In ACPNH, a
      trend toward diminished d3/d3 genotype frequency was observed in the shortest
      height group (height <or=-1 SDS and >or=-2 SDS, n = 60). CONCLUSIONS: Our data
      showed significant differences in the frequency distribution of the d3/fl-GHR
      genotypes between a normally distributed adult height population and short SGA
      children, with the biologically less active fl/fl genotype being almost twice as
      frequent in SGA patients. These data suggest that the d3/fl-GHR polymorphism
      might be considered among the factors that contribute to the phenotypic
      expression of growth.

PMID- 17003088
TI  - Randomized study to characterize glycemic control and short-term pulmonary
      function in patients with type 1 diabetes receiving inhaled human insulin
      (exubera).
AB  - OBJECTIVE: Previous studies with inhaled human insulin [Exubera (EXU); insulin
      human (recombinant DNA origin) Inhalation Powder, Pfizer Inc., New York, NY;
      Nektar Therapeutics, San Carlos, CA) show comparable efficacy to sc insulin and
      small declines in pulmonary function in type 1 and 2 diabetes. This is a detailed
      characterization of short-term efficacy and pulmonary safety profile of EXU.
      RESEARCH DESIGN AND METHODS: In a 24-wk multicenter study, 226 nonsmoking
      patients with type 1 diabetes and normal lung function were randomized to
      intensive regimens of premeal EXU or sc insulin for 12 wk (comparative phase),
      followed by sc insulin for 12 wk (washout phase). Glycosylated hemoglobin,
      hypoglycemia, general adverse events, and pulmonary function were measured.
      Forced expiratory volume in 1 sec and carbon monoxide diffusion capacity were
      measured using standardized equipment and methodology. RESULTS: Comparable
      declines from baseline in glycosylated hemoglobin were observed in both groups
      (0.5%) and sustained throughout the study. There was a higher rate of
      hypoglycemia (risk ratio 1.23; 90% confidence interval 1.16, 1.30) but a lower
      rate of severe hypoglycemia (risk ratio 0.51; 90% confidence interval 0.30, 0.86)
      with EXU vs. sc insulin. The treatment group differences in changes from baseline
      in forced expiratory volume in 1 sec and carbon monoxide diffusion capacity were
      small, occurred within 2 wk of EXU initiation, and were reversible shortly after
      discontinuation. More patients reported mild cough with EXU vs. sc insulin (30.9%
      vs. 7.8%, respectively). CONCLUSIONS: Three months of EXU therapy is as effective
      and well tolerated as intensive sc insulin therapy. This study supports the role
      of EXU in type 1 diabetes.

PMID- 17003089
TI  - Mutational analysis of the vitamin D receptor does not support its candidacy as a
      tumor suppressor gene in parathyroid adenomas.
AB  - CONTEXT: The vitamin D receptor gene (VDR) is a compelling candidate tumor
      suppressor gene for parathyroid adenomas based on existing evidence of the
      vitamin D system's antiproliferative actions in parathyroid and other tissues,
      its reported inhibition of PTH gene transcription, and the decreased expression
      of VDR mRNA and VDR protein observed in parathyroid adenomas. OBJECTIVE: Because
      demonstration of intragenic mutations is required to establish the authenticity
      and primary role in pathogenesis for any candidate tumor suppressor gene, we
      examined the VDR gene in parathyroid adenomas for the presence of such mutations
      and other loss-of-function abnormalities. METHODS AND RESULTS: Genomic DNA
      samples from 37 sporadic parathyroid adenomas and matched normal control DNA from
      the same individuals were subjected to direct sequencing of the entire VDR coding
      region and all intron-exon boundaries. No VDR coding region or junctional
      mutations were identified. The tumors were also analyzed for loss of
      heterozygosity, a frequent mechanism of tumor suppressor gene inactivation, by
      molecular allelotyping at three microsatellite markers located near the VDR gene,
      D12S85, D12S96, and D12S368, and a polymorphism within VDR itself. In all 37
      cases, at least one marker was informative and no tumor-specific loss of
      heterozygosity was observed. CONCLUSION: We found no evidence of allelic loss
      within or near the VDR locus and no mutations within the splice junctions and
      coding regions of the VDR gene in 37 typical sporadic parathyroid adenomas. Thus,
      VDR is most unlikely to commonly serve as a classical tumor suppressor gene in
      sporadic parathyroid adenomas.

PMID- 17003090
TI  - Insulinomas may present with normoglycemia after prolonged fasting but glucose
      stimulated hypoglycemia.
AB  - BACKGROUND: Insulinomas are rare but are the most common cause of
      hyperinsulinemic hypoglycemia in the adult population. Diagnosis of this
      pathology relies on clinical features along with laboratory tests and imaging
      investigations to aid in localization. One of the most robust standard tests used
      for establishing a biochemical diagnosis is the prolonged (72 h) fast. Currently,
      it is recommended that a prolonged supervised fast be performed, at least for 48
      h if not for 72 h, and many would take the absence of hypoglycemia after a 72-h
      fast as evidence excluding the diagnosis. METHODS: We employed prolonged fasts
      and standard glucose tolerance tests, plus imaging studies and surgical
      pathology, in two patients with suspected insulinomas. RESULTS: The prolonged 72
      h fast was normal in both the patients, whereas in both cases a prolonged oral
      glucose tolerance test clearly demonstrated the induction of severe
      hyperinsulinemia followed by significant hypoglycemia. Surgical removal confirmed
      the presence of insulinomas in each case. CONCLUSIONS: Although the sensitivity
      of the 72-h fast is high and still plays an important role in the diagnosis of an
      insulinoma, we suggest that a "normal" test result should be interpreted in the
      light of clinical symptoms.

PMID- 17003091
TI  - Estradiol increases apoptosis in human coronary artery endothelial cells by up
      regulating Fas and Fas ligand expression.
AB  - CONTEXT: In animal models, estrogen inhibits atherogenesis by inhibiting many of
      the early steps of atherosclerotic plaque formation. However, the lack of
      cardioprotective effect by postmenopausal hormone replacement therapy and
      possible increase in cardiovascular events observed during the first year after
      the initiation of hormone replacement therapy may suggest that once the plaque is
      formed, estrogen may have additional effects that may counteract its beneficial
      outcomes. Indeed, the effect of estrogen on plaque stability has not been
      identified. OBJECTIVE: We hypothesized that 17beta-estradiol (E2) may cause
      increased apoptosis in human coronary artery endothelial cells (HCAECs). This
      effect would explain an adverse effect on plaque stability in vivo.
      INTERVENTION(S) AND MAIN OUTCOME MEASURE(S): The effect of E2 on apoptosis, cell
      proliferation, and expression of proapoptotic molecules Fas and Fas ligand (FasL)
      in cultured HCAECs was evaluated. RESULTS: HCAECs in culture treated with E2
      showed an increase in DNA strand breaks and nuclear fragmentation indicative of
      apoptosis. E2 treatment also induced a significant concentration-dependent
      increase in Fas mRNA and protein expressions in HCAECs. Moreover, the expression
      of FasL mRNA and secretion of FasL protein by HCAECs were enhanced in response to
      E2 treatments. CONCLUSIONS: E2 increases the apoptosis in cultured HCAECs.
      Enhanced Fas and FasL expressions in response to E2 suggest that activation of
      the Fas/FasL pathway may be a mediator of the proapoptotic effects of E2 in these
      cells.

PMID- 17003092
TI  - Carotid intimal medial thickness in human immunodeficiency virus-infected women:
      effects of protease inhibitor use, cardiac risk factors, and the metabolic
      syndrome.
AB  - CONTEXT: Little is known regarding carotid intimal medial thickness (IMT) in HIV
      infected women and the risk factors for subclinical atherosclerosis in this
      population, including antiretroviral therapy and the metabolic syndrome.
      OBJECTIVE: Our objective was to assess carotid IMT in relationship to HIV status
      and antiretroviral therapy in HIV-infected women in comparison with healthy age-
      and body mass index (BMI)-matched control subjects. SETTING AND SUBJECTS: The
      study took place at an academic medical center and included 97 HIV-infected women
      compared with 86 age- and BMI-matched healthy control subjects. MAIN OUTCOME
      MEASURES: We assessed carotid IMT, metabolic syndrome, and risk factors for
      increased IMT. RESULTS: Carotid IMT was not increased in HIV-infected women [0.62
      mm (0.57-0.68); median (IQR)] compared with non-HIV-infected women [0.61 mm (0.55
      0.68)] matched for age and BMI (P = 0.07) but was increased significantly among
      HIV patients receiving a protease inhibitor (PI) [0.65 (0.59-0.71) mm] vs. non-PI
      treated patients [0.61 (0.57-0.66) mm] (P < 0.05) and vs. control subjects [0.61
      (0.55-0.68) mm] (P < 0.05). The prevalence of metabolic syndrome was
      significantly increased among the HIV-infected women compared with control
      subjects and particularly in PI- vs. non-PI-treated HIV patients (45 vs. 19%, P =
      0.001). Metabolic syndrome score correlated with IMT among non-HIV patients but
      not among the HIV group. Individual risk factors most strongly associated with
      IMT in multivariate regression modeling in the control group were age and waist
      to-hip ratio, and among the HIV group age and waist circumference. CONCLUSIONS:
      These data demonstrate increased carotid IMT in HIV-infected women receiving PI
      therapy, which may be due to associated metabolic abnormalities related to PI
      therapy or more direct effects of this medication class on the vasculature.
      Additional studies of the mechanisms by which PI uses results in subclinical
      atherosclerosis are needed.

PMID- 17003093
TI  - Visceral and truncal subcutaneous adipose tissue are associated with impaired
      capillary recruitment in healthy individuals.
AB  - CONTEXT: Central adiposity is associated with cardiovascular risk independently
      of total adiposity. Microvascular dysfunction is thought to contribute to obesity
      associated insulin resistance and hypertension and may thus link central
      adiposity with cardiovascular risk. OBJECTIVE: Our objective was to investigate
      how body fat distribution relates to microvascular function and the role of
      adipocytokines in these relationships. DESIGN, SETTING, AND PARTICIPANTS: We
      cross-sectionally studied 51 healthy adults and 29 of their prepubertal children
      born at the VU University Medical Center in Amsterdam. MAIN OUTCOME MEASURES: We
      measured visceral and abdominal sc adiposity with magnetic resonance imaging and
      truncal and peripheral sc adiposity with skinfold thickness. Postocclusive skin
      capillary recruitment was assessed with videomicroscopy. Concentrations of C
      reactive protein, IL-6, and TNF-alpha were combined in an inflammation score.
      RESULTS: In adults, visceral adipose tissue and trunk/extremity skinfold ratio
      were inversely associated with capillary recruitment (partial correlation
      coefficients, -0.32, P = 0.03, and -0.37, P < 0.01, respectively). The
      inflammation score was inversely associated with capillary recruitment (r = 
      0.50; P < 0.01) and statistically explained 41% of the association between
      visceral adipose tissue and capillary recruitment. In children, trunk/extremity
      skinfold ratio was inversely associated with capillary recruitment (r = -0.49; P
      = 0.01), but other measures of adiposity were not. CONCLUSION: Our data in adults
      suggest a role for visceral adiposity and its associated proinflammatory state in
      capillary dysfunction and its possible sequelae such as hypertension and insulin
      resistance. Also, our findings in children and adults suggest that truncal sc
      adiposity is detrimental for capillary perfusion and that this process may start
      before puberty.

PMID- 17003094
TI  - Altered 24-hour blood pressure profiles in children and adolescents with
      classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
AB  - OBJECTIVE: Children and adolescents with classical congenital adrenal hyperplasia
      have been shown to be at risk for obesity associated with higher insulin and
      leptin levels. Because these factors are also known to cause hypertension, the
      aim of this study was to analyze 24-h blood pressure profiles and their relation
      to different clinical and laboratory parameters. DESIGN: Fifty-five subjects,
      aged between 5.3 and 19.0 yr, were enrolled in a prospective, cross-sectional
      study. All patients had genetically proven 21-hydroxylase deficiency and
      underwent ambulatory 24-h blood pressure monitoring during a period off
      school/work. RESULTS (MEDIAN, RANGE): The median body mass index of the cohort
      was significantly elevated [1.09 sd score (SDS), -2.45 to 3.77]. Daytime and
      nighttime systolic blood pressures were also significantly elevated (0.67 SDS, 
      1.5-4.1; 0.63 SDS, -0.91 to 3.3), whereas daytime diastolic blood pressure was
      significantly lowered (-0.81 SDS, -2.6 to 3.2) and normal during the night (0.11
      SDS, -2.0 to 2.0). Overall, there was a normal nocturnal drop of systolic (12.8%,
      2.1-22.8) but not diastolic blood pressure (17.2%, 0.90-25.8). The different
      parameters of systolic and diastolic blood pressures were significantly
      correlated with body mass index and skinfold thickness (r(s) = 0.271-0.486).
      There was no correlation with equivalent hydrocortisone and fludrocortisone
      dosage and laboratory parameters except for serum leptin and insulin.
      CONCLUSIONS: Our data show altered 24-h blood pressure profiles with elevated
      systolic levels correlated with the degree of overweight and obesity, whereas
      normal-weight patients tended to diastolic hypotension.

PMID- 17003095
TI  - Effect of growth hormone therapy on serum adiponectin and resistin levels in
      short, small-for-gestational-age children and associations with cardiovascular
      risk parameters.
AB  - BACKGROUND: Adiponectin and resistin are fat cell-derived hormones, which are
      thought to be respectively protective and disadvantageous with regard to the
      development of cardiovascular disease and diabetes mellitus type 2. Low birth
      weight has been associated with increased risks for the development of these
      diseases. In short, small-for-gestational-age (SGA) children, GH therapy has
      several positive effects regarding cardiovascular risk factors. On the other
      hand, concern has been expressed about the effects of GH therapy on insulin
      sensitivity. METHODS: We measured adiponectin and resistin levels in 136 short
      prepubertal children born SGA and their association with cardiovascular risk
      parameters and growth factors. Also, we compared the levels with normal-statured
      controls. The effect of GH treatment was evaluated in 50 short SGA children vs.
      baseline and vs. an untreated sex- and age-matched SGA control group. RESULTS:
      Short SGA children had similar adiponectin and lower resistin levels, compared
      with normal-statured controls. In GH-treated SGA children, neither adiponectin
      nor resistin levels changed significantly during 2 yr of GH treatment. Compared
      with untreated sex- and age-matched SGA controls, GH-treated SGA children had
      similar adiponectin and lower resistin levels. Adiponectin correlated inversely
      with age but not any cardiovascular risk parameter or growth factor. Higher IGF-I
      levels in GH-treated children were associated with lower resistin levels.
      CONCLUSIONS: Compared with normal-statured controls, short prepubertal SGA
      children had similar adiponectin and lower resistin levels. Two years of GH
      treatment had no effect on their adiponectin and resistin levels.

PMID- 17003096
TI  - Sleep-related breathing disorders in prepubertal children with Prader-Willi
      syndrome and effects of growth hormone treatment.
AB  - CONTEXT: Recently, several cases of sudden death in GH-treated and non-GH
      treated, mainly young Prader-Willi syndrome (PWS), patients were reported. GH
      treatment in PWS results in a remarkable growth response and an improvement of
      body composition and muscle strength. Data concerning effects on respiratory
      parameters, are however, limited. OBJECTIVE: The objective of the study was to
      evaluate effects of GH on respiratory parameters in prepubertal PWS children.
      DESIGN: Polysomnography was performed before GH in 53 children and repeated after
      6 months of GH treatment in 35 of them. PATIENTS: Fifty-three prepubertal PWS
      children (30 boys), with median (interquartile range) age of 5.4 (2.1-7.2) yr and
      body mass index of +1.0 sd score (-0.1-1.7). INTERVENTION: Intervention included
      treatment with GH 1 mg/m2.d. RESULTS: Apnea hypopnea index (AHI) was 5.1 per hour
      (2.8-8.7) (normal 0-1 per hour). Of these, 2.8 per hour (1.5-5.4) were central
      apneas and the rest mainly hypopneas. Duration of apneas was 15.0 sec (13.0
      28.0). AHI did not correlate with age and body mass index, but central apneas
      decreased with age (r = -0.34, P = 0.01). During 6 months of GH treatment, AHI
      did not significantly change from 4.8 (2.6-7.9) at baseline to 4.0 (2.7-6.2; P =
      0.36). One patient died unexpectedly during a mild upper respiratory tract
      infection, although he had a nearly normal polysomnography. CONCLUSIONS: PWS
      children have a high AHI, mainly due to central apneas. Six months of GH
      treatment does not aggravate the sleep-related breathing disorders in young PWS
      children. Our study also shows that monitoring during upper respiratory tract
      infection in PWS children should be considered.

PMID- 17003097
TI  - Insulin action in adipose tissue and muscle in hypothyroidism.
AB  - BACKGROUND: Although insulin resistance in thyroid hormone excess is well
      documented, information on insulin action in hypothyroidism is limited. METHODS:
      To investigate this, a meal was given to 11 hypothyroid (HO; aged 45 +/- 3 yr)
      and 10 euthyroid subjects (EU; aged 42 +/- 4 yr). Blood was withdrawn for 360 min
      from veins (V) draining the anterior abdominal sc adipose tissue and the forearm
      and from the radial artery (A). Blood flow (BF) in adipose tissue was measured
      with 133Xe and in forearm with strain-gauge plethysmography. Tissue glucose
      uptake was calculated as (A-V)glucose(BF), lipoprotein lipase as (A
      V)Triglycerides(BF), and lipolysis as [(V-A)glycerol(BF)]-lipoprotein lipase.
      RESULTS: The HO group had higher glucose and insulin levels than the EU group (P
      < 0.05). In HO vs. EU after meal ingestion (area under curve 0-360 min): 1) BF
      (1290 +/- 79 vs. 1579 +/- 106 ml per 100 ml tissue in forearm and 706 +/- 105 vs.
      1340 +/- 144 ml per 100 ml tissue in adipose tissue) and glucose uptake (464 +/-
      74 vs. 850 +/- 155 micromol per 100 ml tissue in forearm and 208 +/- 42 vs. 406
      +/- 47 micromol per 100 ml tissue in adipose tissue) were decreased (P < 0.05),
      but fractional glucose uptake was similar (28 +/- 6 vs. 33 +/- 6% per minute in
      forearm and 17 +/- 4 vs. 14 +/- 3% per minute in adipose tissue); 2) suppression
      of lipolysis by insulin was similar; and 3) plasma triglycerides were elevated
      (489 +/- 91 vs. 264 +/- 36 nmol/liter.min, P < 0.05), whereas adipose tissue
      lipoprotein lipase (42 +/- 11 vs. 80 +/- 21 micromol per 100 ml tissue) and
      triglyceride clearance (45 +/- 10 vs. 109 +/- 21 ml per 100 ml tissue) were
      decreased in HO (P < 0.05). CONCLUSIONS: In hypothyroidism: 1) glucose uptake in
      muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by
      insulin is not impaired; and 3) hypertriglyceridemia is due to decreased
      clearance by the adipose tissue.

PMID- 17003098
TI  - The relationship between plasma adiponectin concentration and insulin resistance
      is altered in smokers.
AB  - CONTEXT: Low plasma adiponectin concentrations in smokers may contribute to the
      adverse consequences that occur in these individuals. OBJECTIVE: The objective of
      the study was to define the relationship among smoking, plasma adiponectin
      concentrations, insulin resistance, and inflammation. DESIGN: This was a cross
      sectional, observational study with a 2 x 2 factorial design and a prospective
      longitudinal arm. SETTING: The study was conducted at a general clinical research
      center. PARTICIPANTS: Apparently healthy smokers (n = 30) and nonsmokers (n =
      30), subdivided into insulin resistant (IR) (n = 15) and insulin sensitive (IS)
      (n = 15) subgroups participated in the study. INTERVENTION: Intervention included
      pioglitazone administration for 3 months to 12 IR smokers and eight IS smokers.
      MAIN OUTCOME MEASURES: Measures included fasting plasma adiponectin and C
      reactive protein (CRP) concentrations and changes in adiponectin after
      pioglitazone treatment in IR and IS smokers. RESULTS: Being either a smoker or
      having insulin resistance was independently associated with lower adiponectin
      concentrations (P = 0.046 and 0.001, respectively). The difference in mean
      adiponectin concentration between smokers and nonsmokers did not depend on the
      insulin resistance status of the subjects. No difference was detected in average
      CRP concentrations between smokers and nonsmokers (P = 0.18) and between IR and
      IS subjects (P = 0.13). CRP concentrations were unrelated to adiponectin in
      smokers (r = -0.05, P = 0.78) and nonsmokers (r = 0.03, P = 0.86). Finally,
      pioglitazone treatment increased adiponectin concentrations in both IR (P <
      0.001) and IS smokers (P = 0.001). CONCLUSIONS: Plasma adiponectin concentrations
      are lower in smokers and IR subjects and are unrelated to CRP concentrations.
      These findings suggest that low levels of adiponectin in smokers may be
      independent of both insulin resistance and a generalized inflammatory response.

PMID- 17003099
TI  - CYP11B2 -344T/C gene polymorphism and blood pressure in patients with acromegaly.
AB  - CONTEXT: The pathogenesis of increased blood pressure (BP) in acromegaly is
      unclear, and the role of IGF-I levels and the renin-angiotensin-aldosterone
      system (RAAS) in this disease remains controversial. OBJECTIVE AND DESIGN: The
      aim of this study was to investigate the role of gene polymorphisms of the RAAS
      and involved in sodium handling on BP in acromegaly. SETTING AND PATIENTS: We
      conducted a multicentric retrospective study that included 100 consecutive
      patients with acromegaly referred during the period 2000-2003. INTERVENTION: All
      patients were genotyped for ACE I/D, AGT M235T, CYP11B2 -344T/C, B2R -58T/C, and
      alpha-adducin G460W polymorphisms. MAIN OUTCOME MEASURE: We assessed the
      prevalence of hypertension and BP according to the genotype. RESULTS: Patients
      with the CYP11B2 -344CC genotype displayed a significant increase in the risk of
      hypertension compared with patients with CT/TT genotypes (odds ratio = 4.0; 95%
      confidence interval = 1.4-11.6; P = 0.01). Consistently, a significant proportion
      of patients with the CYP11B2 -344CC genotypes were under antihypertensive
      treatment (73.1%) compared with patients with the TT/TC genotypes (38.2%; P =
      0.003). Patients with the -344CC genotype displayed a significant increase in
      systolic BP (10.2 +/- 4.3 mm Hg; P = 0.02) but not a significant increase in
      diastolic BP (2.6 +/- 2.6 mm Hg; P = 0.32) compared with patients with the CT/TT
      genotype. CONCLUSIONS: We have shown an association of the -344T/C CYP11B2 gene
      polymorphism with BP in patients affected by acromegaly. These findings suggest
      that the RAAS is implicated in the pathogenesis of hypertension in acromegaly.

PMID- 17003100
TI  - Odor and irritation thresholds for ammonia: a comparison between static and
      dynamic olfactometry.
AB  - Odor and lateralization (irritation) thresholds (LTs) for ammonia vapor were
      measured using static and dynamic olfactometry. The purpose of the study was to
      explore the test-retest reliability and comparability of dynamic olfactometry
      methodology, generally used to determine odor thresholds following European
      Committee for Standardization guidelines in the context of odor regulations to
      outside emissions, with static olfactometry. Within a 2-week period, odor and LTs
      for ammonia were obtained twice for each method for 24 females. No significant
      differences between methods were found: mean odor detection thresholds (ODTs)
      were 2.6 parts per million (ppm) for either method (P = 0.96), and mean LTs were
      31.7 and 60.9 ppm for the static and dynamic method, respectively (P = 0.07).
      Test-retest reliability was higher for the dynamic than for the static method (r
      = 0.61 vs. 0.14 for ODTs and r = 0.86 vs. 0.45 for LTs). The choice of optimal
      method for any application, however, depends not only on psychometric factors but
      also on practical factors such as physicochemical properties of the compound,
      availability of equipment and expertise, task efficiency, and costs.

PMID- 17003101
TI  - Functional role of beta-adrenergic receptors in the mitogenic action of nicotine
      on gastric cancer cells.
AB  - We previously reported that nicotine promoted gastric cancer cell growth via
      upregulation of cyclooxygenase 2 (COX-2). In the present study, we further
      investigated whether beta-adrenoceptors, protein kinase C (PKC), and
      extracellular signal-regulated kinase-1/2 (ERK1/2) were involved in the
      modulation of COX-2 expression and cell proliferation by nicotine in AGS, a human
      gastric adenocarcinoma cell line. Results showed that nicotine dose dependently
      increased the phosphorylation of EKR1/2 and the expression of AP-1 subunits c-fos
      and c-jun. In this connection, the ERK1/2 inhibitor U0126 abrogated the
      upregulation of AP-1 and COX-2 as well as cell proliferation induced by nicotine.
      Moreover, nicotine induced the translocation of PKC-betaI from cytosol to
      membrane and increased the total levels of PKC expression. Inhibition of PKC by
      staurosporine attenuated nicotine-induced ERK1/2 phosphorylation and COX-2
      expression. Furthermore, atenolol and ICI 118,551, a beta1- and beta2
      adrenoceptor antagonist, respectively, reversed the stimulatory action of
      nicotine on the expression of PKC, ERK1/2 phosphorylation, and COX-2 together
      with cell proliferation. Collectively, these results suggest that nicotine
      stimulates gastric cancer cell growth through the activation of beta
      adrenoceptors and the downstream PKC-betaI/ERK1/2/COX-2 pathway.

PMID- 17003102
TI  - Aryl hydrocarbon receptor activation impairs extracellular matrix remodeling
      during zebra fish fin regeneration.
AB  - Adult zebra fish completely regenerate their caudal (tail) fin following partial
      amputation. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits this
      regenerative process. Proper regulation of transcription, innervation,
      vascularization, and extracellular matrix (ECM) composition is essential for
      complete fin regeneration. Previous microarray studies suggest that genes
      involved in ECM regulation are misexpressed following activation of the aryl
      hydrocarbon receptor. To investigate whether TCDD blocks regeneration by
      impairing ECM remodeling, male zebra fish were i.p. injected with 50 ng/g TCDD or
      vehicle, and caudal fins were amputated. By 3 days postamputation (dpa), the
      vascular network in the regenerating fin of TCDD-exposed fish was disorganized
      compared to vehicle-exposed animals. Furthermore, immunohistochemical staining
      revealed that axonal outgrowth was impacted by TCDD as early as 3 dpa.
      Histological analysis demonstrated that TCDD exposure leads to an accumulation of
      collagen at the end of the fin ray just distal to the amputation site by 3 dpa.
      Mature lepidotrichial-forming cells (fin ray-forming cells) were not observed in
      the fins of TCDD-treated fish. The capacity to metabolize ECM was also altered by
      TCDD exposure. Quantitative real-time PCR studies revealed that the aryl
      hydrocarbon pathway is active and that matrix-remodeling genes are expressed in
      the regenerate following TCDD exposure.

PMID- 17003103
TI  - Photochemotherapeutic agent 8-methoxypsoralen induces cytochrome P450 3A4 and
      carboxylesterase HCE2: evidence on an involvement of the pregnane X receptor.
AB  - 8-Methoxypsoralen (8-MOP) is a prototype photochemotherapeutic agent and used to
      treat various skin disorders such as psoriasis and cutaneous T-cell lymphoma.
      Animal studies demonstrate that repeated treatment with 8-MOP markedly increases
      the capacity of drug metabolism. In this study, we report that 8-MOP is a potent
      inducer of cytochrome P450 3A4 (CYP3A4) and carboxylesterase 2 (HCE2), two major
      human enzymes that catalyze oxidative and hydrolytic reactions, respectively. In
      human primary hepatocytes, 8-MOP markedly induced the expression of CYP3A4
      (approximately sixfold) and HCE2 (approximately threefold) and the induction
      occurred in a concentration-dependent manner (0-50 microM). RNA interference of
      the expression of the pregnane X receptor (PXR) proportionally decreased the
      induction. In a reporter assay, 8-MOP stimulated both CYP3A4 and HCE2 promoters,
      and the stimulation was enhanced by cotransfection of PXR. Several natural
      variants of PXR differed markedly from the wild-type receptor in responding to 8
      MOP. In addition to human PXR (hPXR), 8-MOP activated rat PXR, and the activation
      was comparable to that of hPXR (EC(50) = approximately 14 microM). PXR is
      recognized as a master regulator of the genes encoding drug-metabolizing enzymes
      and transporters. The involvement of PXR in 8-MOP induction suggests that this
      chemotherapeutic agent causes a broader range of drug-drug interactions, and the
      differential activation of certain PXR variants suggests that the magnitude of
      the interactions varies from person to person.

PMID- 17003104
TI  - Different abilities of the four FGFRs to mediate FGF-1 translocation are linked
      to differences in the receptor C-terminal tail.
AB  - Members of the fibroblast growth factor family bind to one or more of the four
      closely related membrane-spanning FGF receptors. In addition to signaling through
      the receptors, exogenous FGF-1 and FGF-2 are endocytosed and translocated to the
      cytosol and nucleus where they stimulate RNA and DNA synthesis. Here we have
      studied the ability of the four FGF receptors to facilitate translocation of
      exogenous FGF-1 to the cytosol and nucleus. FGFR1 and FGFR4 were able to mediate
      translocation, whereas FGFR2 and FGFR3 completely lacked this ability. By
      analyzing mutant FGFRs we found that the tyrosine kinase domain could be deleted
      from FGFR1 without abolishing translocation, whereas the C-terminal tail of the
      FGFRs, constituted by approximately 50 amino acids downstream of the kinase
      domain, plays a crucial role in FGF-1 translocation. Three amino acids residues
      within the C-terminal tail were found to be of particular importance for
      translocation. For FGFR2, the two amino acid substitutions Q774M and P800H were
      sufficient to enable the receptor to support FGF-1 translocation. The results
      demonstrate a striking diversity in function of the four FGFRs determined by
      their C-terminal domain.

PMID- 17003105
TI  - CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage.
AB  - CDC25B is one of the three human phosphatases that activate the CDK-cyclin
      complexes, thereby triggering cell-cycle progression and division. Commitment to
      early mitotic events depends on the activation of a centrosomal pool of CDK1
      cyclin-B1, and CDC25B is thought to be involved in initiating this centrosomal
      CDK1-cyclin-B1 activity. Centrosome-associated checkpoint kinase 1 (CHK1) has
      been proposed to contribute to the proper timing of a normal cell division cycle
      by inhibiting the activation of the centrosomal pool of CDK1. Here, we show that
      CDC25B is phosphorylated by CHK1 in vitro on multiple residues, including S230
      and S563. We demonstrate these phosphorylations occur in vivo and that they are
      dependent on CHK1 activity. S230 CHK1-mediated phosphorylation is detected in
      cell extracts during S phase and G2 phase in the absence of DNA damage. We show
      that the S230-phosphorylated form of CDC25B is located at the centrosome from
      early S phase until mitosis. Furthermore, mutation of S230 to alanine increases
      the mitotic-inducing activity of CDC25B. Our results support a model in which,
      under normal cell cycle conditions and in the absence of DNA damage, CHK1
      constitutively phosphorylates CDC25B during interphase and thus prevents the
      premature initiation of mitosis by negatively regulating the activity of CDC25B
      at the centrosome.

PMID- 17003106
TI  - Role of the C-terminal di-leucine motif of 5-HT1A and 5-HT1B serotonin receptors
      in plasma membrane targeting.
AB  - The 5-HT1A and 5-HT1B serotonin receptors exhibit different subcellular
      localizations in neurons. Evidence has been reported that the C-terminal domain
      is involved in the somato-dendritic and axonal targeting of 5-HT1AR and 5-HT1BR,
      respectively. Here we analyzed the consequences of the mutation of a di-leucine
      motif and palmitoylated cysteines within this domain. Replacement of I414-I415 by
      a di-alanine in 5-HT1AR led to endoplasmic reticulum (ER) sequestration of the
      corresponding mutant expressed in cell lines as well as in hippocampal neurons in
      culture. Furthermore, di-leucine-mutated receptors were unable to bind 5-HT1A
      agonists and presented a major deficit in their glycosylation state, suggesting
      that they are misfolded. By contrast, mutation of the di-leucine motif in the C
      terminal domain of 5-HT1BR had no major consequence on its subcellular targeting.
      However, in the case of the 1ActB chimera (substitution of the C-terminal domain
      of the 5-HT1BR into 5-HT1AR), this mutation was also found to cause sequestration
      within the ER. Replacement of palmitoylated cysteines by serines had no
      consequence on either receptor type. These data indicate that the di-leucine
      motif of the 5-HT1AR and 5-HT1BR tails is implicated in proper folding of these
      receptors, which is necessary for their ER export.

PMID- 17003107
TI  - Fab1p and AP-1 are required for trafficking of endogenously ubiquitylated cargoes
      to the vacuole lumen in S. cerevisiae.
AB  - In S. cerevisiae synthesis of phosphatidylinositol (3,5)-bisphosphate
      [PtdIns(3,5)P2] by Fab1p is required for several cellular events, including an as
      yet undefined step in the ubiquitin-dependent trafficking of some integral
      membrane proteins from the trans-Golgi network to the vacuole lumen. AP-1 is a
      heterotetrameric clathrin adaptor protein complex that binds cargo proteins and
      clathrin coats, and regulates bi-directional protein trafficking between the
      trans-Golgi network and the endocytic/secretory pathway. Like fab1Delta cells, AP
      1 complex component mutants have lost the ability to traffic ubiquitylated
      cargoes to the vacuole lumen - the first demonstration that AP-1 is required for
      this process. Deletion mutants of AP-1 complex components are compromised in
      their ability to synthesize PtdIns(3,5)P2, indicating that AP-1 is required for
      correct in vivo activation of Fab1p. Furthermore, wild-type protein sorting can
      be restored in AP-1 mutants by overexpression of Fab1p, implying that the protein
      sorting defect in these cells is as a result of disruption of PtdIns(3,5)P2
      synthesis. Finally, we show that Fab1p and Vac14p, an activator of Fab1p, are
      also required for another AP-1-dependent process: chitin-ring deposition in
      chs6Delta cells. Our data imply that AP-1 is required for some Fab1p and
      PtdIns(3,5)P2-dependent processes.

PMID- 17003108
TI  - Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis.
AB  - Myocyte enhancer factors (MEF2s) bind to muscle-specific promoters and activate
      transcription. Drosophila Mef2 is essential for Drosophila heart development,
      however, neither MEF2C nor MEF2B are essential for the early stages of murine
      cardiomyogenesis. Although Mef2c-null mice were defective in the later stages of
      heart morphogenesis, differentiation of cardiomyocytes still occurred. Since
      there are four isoforms of MEF2 factors (MEF2A, MEF2B, MEF2C and MEF2D), the
      ability of cells to differentiate may have been confounded by genetic redundancy.
      To eliminate this variable, the effect of a dominant-negative MEF2 mutant
      (MEF2C/EnR) during cardiomyogenesis was examined in transgenic mice and P19
      cells. Targeting the expression of MEF2C/EnR to cardiomyoblasts using an Nkx2-5
      enhancer in the P19 system resulted in the loss of both cardiomyocyte development
      and the expression of GATA4, BMP4, Nkx2-5 and MEF2C. In transiently transgenic
      mice, MEF2C/EnR expression resulted in embryos that lacked heart structures and
      exhibited defective differentiation. Our results show that MEF2C, or genes
      containing MEF2 DNA-binding sites, is required for the efficient differentiation
      of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of
      MEF2 from Drosophila to mammals.

PMID- 17003109
TI  - Changes in lamina structure are followed by spatial reorganization of
      heterochromatic regions in caspase-8-activated human mesenchymal stem cells.
AB  - Apoptosis is fundamental to the regulation of homeostasis of stem cells in vivo.
      Whereas the pathways underlying the molecular and biochemical details of nuclear
      breakdown that accompanies apoptosis have been elucidated, the precise nature of
      nuclear reorganization that precedes the demolition phase is not fully
      understood. Here, we expressed an inducible caspase-8 in human mesenchymal stem
      cells, and quantitatively followed the early changes in nuclear organization
      during apoptosis. We found that caspase-8 induces alteration of the nuclear
      lamina and a subsequent spatial reorganization of both centromeres, which are
      shifted towards a peripheral localization, and telomeres, which form aggregates.
      This nuclear reorganization correlates with caspase-3 sensitivity of lamina
      proteins, because the expression of lamin mutant constructs with caspase-3
      hypersensitivity resulted in a caspase-8-independent appearance of lamina
      intranuclear structures and telomere aggregates, whereas application of a caspase
      inhibitor restrains these changes in nuclear reorganization. Notably, upon
      activation of apoptosis, we observed no initial changes in the spatial
      organization of the promyelocytic leukemia nuclear bodies (PML-NBs). We suggest
      that during activation of the caspase-8 pathway changes in the lamina structure
      precede changes in heterochromatin spatial organization, and the subsequent
      breakdown of lamina and PML-NB.

PMID- 17003110
TI  - PAR3 acts as a molecular organizer to define the apical domain of chick
      neuroepithelial cells.
AB  - Neural progenitors in the vertebrate nervous system are fully polarized
      epithelial cells, with intercellular junctions at the apical region. These
      progenitor cells remain within the neuroepithelium throughout neurogenesis, and
      will ultimately give rise to all the neurons in the mature nervous system. We
      have addressed the role of the PAR polarity complex in vertebrate neuroepithelial
      polarity and show that PAR3 functions as the initial scaffold to assemble and
      organize the PAR complex at the apical region of neuroepithelial cells,
      coordinating also the recruitment of additional polarity complexes and junction
      associated proteins to the same region, while restricting other polarity proteins
      to the basolateral membrane. We propose that PAR3 acts as a molecular organizer
      to connect the acquisition of apico-basal polarity with the positioning and
      formation of junctional structures in neuroepithelial cells, a function of upmost
      importance for the morphogenesis of embryonic neural tissue and the process of
      neurogenesis.

PMID- 17003111
TI  - Imatinib spells BAD news for Bcr/abl-positive leukemias.

PMID- 17003112
TI  - Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the
      hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF
      (FIH).
AB  - Studies on hypoxia-sensitive pathways have revealed a series of Fe(II)-dependent
      dioxygenases that regulate hypoxia-inducible factor (HIF) by prolyl and
      asparaginyl hydroxylation. The recognition of these unprecedented signaling
      processes has led to a search for other substrates of the HIF hydroxylases. Here
      we show that the human HIF asparaginyl hydroxylase, factor inhibiting HIF (FIH),
      also efficiently hydroxylates specific asparaginyl (Asn)-residues within proteins
      of the IkappaB family. After the identification of a series of ankyrin repeat
      domain (ARD)-containing proteins in a screen for proteins interacting with FIH,
      the ARDs of p105 (NFKB1) and IkappaBalpha were shown to be efficiently
      hydroxylated by FIH at specific Asn residues in the hairpin loops linking
      particular ankyrin repeats. The target Asn residue is highly conserved as part of
      the ankyrin consensus, and peptides derived from a diverse range of ARD
      containing proteins supported FIH enzyme activity. These findings demonstrate
      that this type of protein hydroxylation is not restricted to HIF and strongly
      suggest that FIH-dependent ARD hydroxylation is a common occurrence, potentially
      providing an oxygen-sensitive signal to a diverse range of processes.

PMID- 17003114
TI  - Profile of Daniel J. Cosgrove.

PMID- 17003113
TI  - Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer
      associated stromal cells and can promote tumor cell proliferation.
AB  - Although tissue microenvironments play critical roles in epithelial development
      and tumorigenesis, the factors mediating these effects are poorly understood. In
      this work, we used a genomic approach to identify factors produced by cells in
      the microenvironment of basal cell carcinoma (BCC) of the skin, one of the most
      common human cancers. The global gene expression programs of stromal cell
      cultures derived from human BCCs showed consistent, systematic differences from
      those derived from nontumor skin. The gene most consistently expressed at a
      higher level in BCC tumor stromal cells compared with those from nontumor skin
      was GREMLIN 1, which encodes a secreted antagonist of the bone morphogenetic
      protein (BMP) pathway. BMPs and their antagonists are known to play a crucial
      role in stem and progenitor cell biology as regulators of the balance between
      expansion and differentiation. Consistent with the hypothesis that BMP
      antagonists might have a similar role in cancer, we found GREMLIN 1 expression in
      the stroma of human BCC tumors but not in normal skin in vivo. Furthermore, BMP 2
      and 4 are expressed by BCC cells. Ex vivo, BMP inhibits, and Gremlin 1 promotes,
      proliferation of cultured BCC cells. We further found that GREMLIN 1 is expressed
      by stromal cells in many carcinomas but not in the corresponding normal tissue
      counterparts that we examined. Our data suggest that BMP antagonists may be
      important constituents of tumor stroma, providing a favorable microenvironment
      for cancer cell survival and expansion in many cancers.

PMID- 17003115
TI  - Follicle-stimulating hormone stimulates TNF production from immune cells to
      enhance osteoblast and osteoclast formation.
AB  - Declining estrogen production after menopause causes osteoporosis in which the
      resorption of bone exceeds the increase in bone formation. We recently found that
      mice deficient in the beta-subunit of follicle-stimulating hormone (FSHbeta) are
      protected from bone loss despite severe estrogen deficiency. Here we show that
      FSHbeta-deficient mice have lowered TNFalpha levels. However, TNFalpha-deficient
      mice are resistant to hypogonadal bone loss despite having elevated FSH,
      suggesting that TNFalpha is critical to the effect of FSH on bone mass. We find
      that FSH directly stimulates TNFalpha production from bone marrow granulocytes
      and macrophages. We also explore how TNFalpha up-regulation induces bone loss. By
      modeling the known actions of TNFalpha, we attribute the high-turnover bone loss
      to an expanded osteoclast precursor pool, together with enhanced osteoblast
      formation. TNFalpha inhibits osteoblastogenesis in the presence of ascorbic acid
      in culture medium, but in its absence this effect becomes stimulatory; thus,
      ascorbic acid reverses the true action of TNFalpha. Likewise, ascorbic acid
      blunts the effects of TNFalpha in stimulating osteoclast formation. We propose
      that hypogonadal bone loss is caused, at least in part, by enhanced FSH
      secretion, which in turn increases TNFalpha production to expand the number of
      bone marrow osteoclast precursors. Ascorbic acid may prevent FSH-induced
      hypogonadal bone loss by modulating the catabolic actions of TNFalpha.

PMID- 17003116
TI  - When motion appears stopped: stereo motion standstill.
AB  - Motion standstill is different from the usual perceptual experiences associated
      with objects in motion. In motion standstill, a pattern that is moving quite
      rapidly is perceived as being motionless, and yet its details are not blurred but
      clearly visible. We revisited motion standstill in dynamic random-dot stereograms
      similar to those first used by Julesz and Payne [Julesz B, Payne R (1968) Vision
      Res 8:433-444]. Three improvements were made to their paradigm to avoid possible
      confounds: The temporal frequency of the motion stimuli was manipulated
      independently from that of individual stereo gratings so that the failure of
      motion perception is not due to inability to compute stereo. The motion of the
      stereo gratings was continuous across the visual field so that the perceived
      pattern in motion standstill was not a simple average of a back-and-forth display
      wobble over time. Observers discriminated three spatial frequencies to
      demonstrate pattern recognition. Three objective psychophysical methods, instead
      of merely self-report, were used to objectively demonstrate motion standstill.
      Our results confirm that motion standstill occurs in dynamic random-dot
      stereogram motion displays at 4-6 Hz. Motion standstill occurs when the stimulus
      spatiotemporal frequency combination exceeds that of the salience-based third
      order motion system in a spatiotemporal frequency range in which the shape and
      depth systems still function. The ability of shape systems to extract a
      representative image from a series of moving samples is a significant component
      of a biological system's ability to derive a stable perceptual world from a
      constantly changing visual environment.

PMID- 17003117
TI  - Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide
      nanoparticles and calmodulin.
AB  - We describe a family of calcium indicators for magnetic resonance imaging (MRI),
      formed by combining a powerful iron oxide nanoparticle-based contrast mechanism
      with the versatile calcium-sensing protein calmodulin and its targets. Calcium
      dependent protein-protein interactions drive particle clustering and produce up
      to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A
      variant based on conjugates of wild-type calmodulin and the peptide M13 reports
      concentration changes near 1 microM Ca(2+), suitable for detection of elevated
      intracellular calcium levels. The midpoint and cooperativity of the response can
      be tuned by mutating the protein domains that actuate the sensor. Robust MRI
      signal changes are achieved even at nanomolar particle concentrations (<1 microM
      in calmodulin) that are unlikely to buffer calcium levels. When combined with
      technologies for cellular delivery of nanoparticulate agents, these sensors and
      their derivatives may be useful for functional molecular imaging of biological
      signaling networks in live, opaque specimens.

PMID- 17003119
TI  - Reconstruction of New Orleans after Hurricane Katrina: a research perspective.
AB  - Four propositions drawn from 60 years of natural hazard and reconstruction
      research provide a comparative and historical perspective on the reconstruction
      of New Orleans after Hurricane Katrina. Decisions taken over its 288-year history
      that have made New Orleans so vulnerable to Katrina reflect a long-term pattern
      of societal response to hazard events--reducing consequences to relatively
      frequent events, and increasing vulnerability to very large and rare events. Thus
      Katrina's consequences for New Orleans were truly catastrophic--accounting for
      most of the estimated 1,570 deaths of Louisiana residents and $40-50 billion in
      monetary losses. A comparative sequence and timing of recovery provides a
      calendar of historical experience against which to gauge progress in
      reconstruction. Using this calendar, the emergency post-disaster period appears
      to be longer in duration than that of any other studied disaster. The restoration
      period, the time taken to restore urban services for the smaller population, is
      in keeping with or ahead of historical experience. The effort to reconstruct the
      physical environment and urban infrastructure is likely to take 8-11 years.
      Conflicting policy goals for reconstruction of rapid recovery, safety,
      betterment, and equity are already evident. Actions taken demonstrate the rush to
      rebuild the familiar in contrast to planning efforts that emphasize betterment.
      Because disasters tend to accelerate existing economic, social, and political
      trends, the large losses in housing, population, and employment after Katrina are
      likely to persist and, at best, only partly recover. However, the possibility of
      breaking free of this gloomy trajectory is feasible and has some historical
      precedent.

PMID- 17003118
TI  - A hypothesis for vulnerable plaque rupture due to stress-induced debonding around
      cellular microcalcifications in thin fibrous caps.
AB  - In this article, we advance a hypothesis for the rupture of thin fibrous cap
      atheroma, namely that minute (10-mum-diameter) cellular-level microcalcifications
      in the cap, which heretofore have gone undetected because they lie below the
      visibility of current in vivo imaging techniques, cause local stress
      concentrations that lead to interfacial debonding. New theoretical solutions are
      presented for the local stress concentration around these minute spherical
      inclusions that predict a nearly 2-fold increase in interfacial stress that is
      relatively insensitive to the location of the hypothesized microinclusions in the
      cap. To experimentally confirm the existence of the hypothesized cellular-level
      microcalcifications, we examined autopsy specimens of coronary atheromatous
      lesions using in vitro imaging techniques whose resolution far exceeds
      conventional magnetic resonance imaging, intravascular ultrasound, and optical
      coherence tomography approaches. These high-resolution imaging modalities, which
      include confocal microscopy with calcium-specific staining and micro-computed
      tomography imaging, provide images of cellular-level calcifications within the
      cap proper. As anticipated, the minute inclusions in the cap are very rare
      compared with the numerous calcified macrophages observed in the necrotic core.
      Our mathematical model predicts that inclusions located in an area of high
      circumferential stress (>300 kPa) in the cap can intensify this stress to nearly
      600 kPa when the cap thickness is <65 microm. The most likely candidates for the
      inclusions are either calcified macrophages or smooth muscle cells that have
      undergone apoptosis.

PMID- 17003120
TI  - Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung.
AB  - Arginine is an amino acid that serves as a substrate for nitric oxide synthase
      and arginase. As such, arginine has the potential to influence diverse
      fundamental processes in the lung. Here we report that the arginine transport
      protein, cationic amino acid transporter (CAT)2, has a critical role in
      regulating lung inflammatory responses. Analysis of CAT2-deficient mice revealed
      spontaneous inflammation in the lung. Marked eosinophilia, associated with up
      regulation of eotaxin-1, was present in the bronchoalveolar lavage fluid of 3
      week-old CAT2-deficient mice. The eosinophilia was gradually replaced by
      neutrophilia in adult mice, while eotaxin-1 levels decreased and GRO-alpha levels
      increased. Despite the presence of activated alveolar macrophages in CAT2
      deficient mice, NO production was compromised in these cells. Examination of
      dendritic cell activation, which can be affected by NO release, indicated
      increased dendritic cell activation in the lungs of CAT2-deficient mice. This
      process was accompanied by an increase in the number of memory T cells. Thus, our
      data suggest that CAT2 regulates anti-inflammatory processes in the lungs via
      regulation of dendritic cell activation and subsequent T cell responses.

PMID- 17003121
TI  - Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal
      toxicity.
AB  - Menkes disease, a fatal neurodegenerative disorder resulting in seizures,
      hypotonia, and failure to thrive, is due to inherited loss-of-function mutations
      in the gene encoding a copper-transporting ATPase (Atp7a) on the X chromosome.
      Although affected patients exhibit signs and symptoms of copper deficiency, the
      mechanisms resulting in neurologic disease remain unknown. We recently discovered
      that Atp7a is required for the production of an NMDA receptor-dependent
      releasable copper pool within hippocampal neurons, a finding that suggests a role
      for copper in activity-dependent modulation of synaptic activity. In support of
      this hypothesis, we now demonstrate that copper chelation exacerbates NMDA
      mediated excitotoxic cell death in primary hippocampal neurons, whereas the
      addition of copper is specifically protective and results in a significant
      decrease in cytoplasmic Ca(2+) levels after NMDA receptor activation. Consistent
      with the known neuroprotective effect of NMDA receptor nitrosylation, we show
      here that this protective effect of copper depends on endogenous nitric oxide
      production in hippocampal neurons, demonstrating in vivo links among
      neuroprotection, copper metabolism, and nitrosylation. Atp7a is required for
      these copper-dependent effects: Hippocampal neurons isolated from newborn Mo(br)
      mice reveal a marked sensitivity to endogenous glutamate-mediated NMDA receptor
      dependent excitotoxicity in vitro, and mild hypoxic/ischemic insult to these mice
      in vivo results in significantly increased caspase 3 activation and neuronal
      injury. Taken together, these data reveal a unique connection between copper
      homeostasis and NMDA receptor activity that is of broad relevance to the
      processes of synaptic plasticity and excitotoxic cell death.

PMID- 17003122
TI  - A class of iron chelators with a wide spectrum of potent antitumor activity that
      overcomes resistance to chemotherapeutics.
AB  - Novel chemotherapeutics with marked and selective antitumor activity are
      essential to develop, particularly those that can overcome resistance to
      established therapies. Iron (Fe) is critical for cell-cycle progression and DNA
      synthesis and potentially represents a novel molecular target for the design of
      new anticancer agents. The aim of this study was to evaluate the antitumor
      activity and Fe chelation efficacy of a new class of Fe chelators using human
      tumors. In this investigation, the ligands showed broad antitumor activity and
      could overcome resistance to established antitumor agents. The in vivo efficacy
      of the most effective chelator identified, di-2-pyridylketone-4,4,-dimethyl-3
      thiosemicarbazone (Dp44mT), was assessed by using a panel of human xenografts in
      nude mice. After 7 weeks, net growth of a melanoma xenograft in Dp44mT-treated
      mice was only 8% of that in mice treated with vehicle. In addition, no
      differences in these latter animals were found in hematological indices between
      Dp44mT-treated mice and controls. No marked systemic Fe depletion was observed
      comparing Dp44mT- and vehicle-treated mice, probably because of the very low
      doses required to induce anticancer activity. Dp44mT caused up-regulation of the
      Fe-responsive tumor growth and metastasis suppressor Ndrg1 in the tumor but not
      in the liver, indicating a potential mechanism of selective anticancer activity.
      These results indicate that the novel Fe chelators have potent and broad
      antitumor activity and can overcome resistance to established chemotherapeutics
      because of their unique mechanism of action.

PMID- 17003123
TI  - Nonhomologous chromosomal integration of foreign DNA is completely dependent on
      MUS-53 (human Lig4 homolog) in Neurospora.
AB  - Homologous integration of a foreign DNA segment into a chromosomal target
      sequence enables precise disruption or replacement of genes of interest and
      provides an effective means to analyze gene function. However, integration after
      transformation is predominantly nonhomologous in most species other than yeast.
      Here, we show that homologous integration in the filamentous fungus Neurospora
      requires the homologous-recombination proteins MEI-3 (yeast Rad51 homolog) and
      MUS-25 (yeast Rad54 homolog), whereas nonhomologous integration requires
      nonhomologous end-joining protein MUS-52 (yeast Ku80 homolog). Two additional
      minor integration pathways are present, one MEI-3-independent and homologous, the
      other MUS-52-independent and nonhomologous. Homologous and nonhomologous
      mechanisms compete when external DNA is integrated. In Neurospora, both
      nonhomologous integration pathways, MUS-52-dependent and MUS-52-independent,
      require MUS-53 (a homolog of human Lig4), which functions in the final step of
      nonhomologous end-joining. Because nonhomologous integration is eliminated in a
      LIG4-disrupted strain, integration occurs only at the targeted site in mus-53
      mutants, making them an extremely efficient and safe host for gene targeting.

PMID- 17003124
TI  - Two ligand-binding sites in the O2-sensing signal transducer HemAT: implications
      for ligand recognition/discrimination and signaling.
AB  - We have identified a ligand (CO) accommodation cavity in the signal transducer
      sensor protein HemAT (heme-based aerotactic transducer) that allows us to gain
      single-molecule insights into the mechanism of gas sensor proteins. Specific
      mutations that are distal and proximal to the heme were designed to perturb the
      electrostatic field near the ligand that is bound to the heme and near the
      accommodated ligand in the cavity. We report the detection of a second site in
      heme proteins in which the exogenous ligand is accommodated in an internal
      cavity. The conformational gate that directs the ligand-migration pathway from
      the distal to the proximal site of the heme, where the ligand is trapped, has
      been identified. The data provide evidence that the heme pocket is the specific
      ligand trap and suggest that the regulatory mechanism may be tackled starting
      from more than one position in the protein. Based on the results, we propose a
      dynamic coupling between the two distinct binding sites as the underlying
      allosteric mechanism for gas recognition/discrimination that triggers a
      conformational switch for signaling by the oxygen sensor protein HemAT.

PMID- 17003125
TI  - FLASH is required for histone transcription and S-phase progression.
AB  - Cajal bodies are nuclear subdomains that are involved in maturation of small
      ribonucleoproteins and frequently associate with small nuclear RNA and histone
      gene clusters in interphase cells. We have recently identified FADD-like IL-1beta
      converting enzyme (FLICE) associated huge protein (FLASH) as an essential
      component of Cajal bodies. Here we show that FLASH associates with nuclear
      protein, ataxia-telangiectasia, a component of the cell-cycle-dependent histone
      gene transcription machinery. Reduction of FLASH expression by RNA interference
      results in disruption of the normal Cajal body architecture and relocalization of
      nuclear protein, ataxia-telangiectasia. Furthermore, FLASH down-regulation
      results in a clear reduction of histone transcription and a dramatic S-phase
      arrest of the cell cycle. Chromatin immunoprecipitation reveals that FLASH
      interacts with histone gene promoter sequences. These results identify FLASH as
      an important component of the machinery required for histone precursor mRNA
      expression and cell-cycle progression.

PMID- 17003126
TI  - FLASH is an essential component of Cajal bodies.
AB  - Cajal bodies are small nuclear organelles with a number of nuclear functions.
      Here we show that FLICE-associated huge protein (FLASH), originally described as
      a component of the apoptosis signaling pathway, is mainly localized in Cajal
      bodies and is essential for their structure. Reduction in FLASH expression by
      short hairpin RNA results in disruption of the normal architecture of the Cajal
      body and relocalization of its components. Because the function of FLASH in the
      apoptosis receptor signaling pathway has been strongly questioned, we have now
      identified a clear function for this protein.

PMID- 17003127
TI  - Direct spectroscopic detection of a C-H-cleaving high-spin Fe(IV) complex in a
      prolyl-4-hydroxylase.
AB  - The Fe(II)- and alpha-ketoglutarate (alphaKG)-dependent dioxygenases use
      mononuclear nonheme iron centers to effect hydroxylation of their substrates and
      decarboxylation of their cosubstrate, alphaKG, to CO(2) and succinate. Our recent
      dissection of the mechanism of taurine:alphaKG dioxygenase (TauD), a member of
      this enzyme family, revealed that two transient complexes accumulate during
      catalysis in the presence of saturating substrates. The first complex contains
      the long-postulated C-H-cleaving Fe(IV)-oxo intermediate, J, and the second is an
      enzyme.product(s) complex. Here, we demonstrate the accumulation of two transient
      complexes in the reaction of a prolyl-4-hydroxylase (P4H), a functional homologue
      of human alphaKG-dependent dioxygenases with essential roles in collagen
      biosynthesis and oxygen sensing. The kinetic and spectroscopic properties of
      these two P4H complexes suggest that they are homologues of the TauD
      intermediates. Most notably, the first exhibits optical absorption and Mossbauer
      spectra similar to those of J and, like J, a large substrate deuterium kinetic
      isotope on its decay. The close correspondence of the accumulating states in the
      P4H and TauD reactions supports the hypothesis of a conserved mechanism for
      substrate hydroxylation by enzymes in this family.

PMID- 17003128
TI  - Characterization and prediction of protein-protein interactions within and
      between complexes.
AB  - Databases of experimentally determined protein interactions provide information
      on binary interactions and on involvement in multiprotein complexes. These data
      are valuable for understanding the general properties of the interaction between
      proteins as well as for the development of prediction schemes for unknown
      interactions. Here we analyze experimentally determined protein interactions by
      measuring various sequence, genomic, transcriptomic, and proteomic attributes of
      each interacting pair in the yeast Saccharomyces cerevisiae. We find that
      dividing the data into two groups, one that includes binary interactions within
      protein complexes (stable) and another that includes binary interactions that are
      not within complexes (transient), enables better characterization of the
      interactions by the different attributes and improves the prediction of new
      interactions. This analysis revealed that most attributes were more indicative in
      the set of intracomplex interactions. Using this data set for training, we
      integrated the different attributes by logistic regression and developed a
      predictive scheme that distinguishes between interacting and noninteracting
      protein pairs. Analysis of the logistic-regression model showed that one of the
      strongest contributors to the discrimination between interacting and
      noninteracting pairs is the presence of distinct pairs of domain signatures that
      were suggested previously to characterize interacting proteins. The predictive
      algorithm succeeds in identifying both intracomplex and other interactions
      (possibly the more stable ones), and its correct identification rate is 2-fold
      higher than that of large-scale yeast two-hybrid experiments.

PMID- 17003129
TI  - Legume genome evolution viewed through the Medicago truncatula and Lotus
      japonicus genomes.
AB  - Genome sequencing of the model legumes, Medicago truncatula and Lotus japonicus,
      provides an opportunity for large-scale sequence-based comparison of two genomes
      in the same plant family. Here we report synteny comparisons between these
      species, including details about chromosome relationships, large-scale synteny
      blocks, microsynteny within blocks, and genome regions lacking clear
      correspondence. The Lotus and Medicago genomes share a minimum of 10 large-scale
      synteny blocks, each with substantial collinearity and frequently extending the
      length of whole chromosome arms. The proportion of genes syntenic and collinear
      within each synteny block is relatively homogeneous. Medicago-Lotus comparisons
      also indicate similar and largely homogeneous gene densities, although gene
      containing regions in Mt occupy 20-30% more space than Lj counterparts, primarily
      because of larger numbers of Mt retrotransposons. Because the interpretation of
      genome comparisons is complicated by large-scale genome duplications, we describe
      synteny, synonymous substitutions and phylogenetic analyses to identify and date
      a probable whole-genome duplication event. There is no direct evidence for any
      recent large-scale genome duplication in either Medicago or Lotus but instead a
      duplication predating speciation. Phylogenetic comparisons place this duplication
      within the Rosid I clade, clearly after the split between legumes and Salicaceae
      (poplar).

PMID- 17003130
TI  - Structural and mutational studies of the amino acid-editing domain from
      archaeal/eukaryal phenylalanyl-tRNA synthetase.
AB  - To achieve accurate aminoacylation of tRNAs with their cognate amino acids,
      errors in aminoacylation are corrected by the "editing" mechanism in several
      aminoacyl-tRNA synthetases. Phenylalanyl-tRNA synthetase (PheRS) hydrolyzes, or
      edits, misformed tyrosyl-tRNA with its editing domain in the beta subunit. We
      report the crystal structure of an N-terminal fragment of the PheRS beta subunit
      (PheRS-beta(N)) from the archaeon, Pyrococcus horikoshii, at 1.94-A resolution.
      PheRS-beta(N) includes the editing domain B3/4, which has archaea/eukarya
      specific insertions/deletions and adopts a different orientation relative to
      other domains, as compared with that of bacterial PheRS. Surprisingly, most
      residues constituting the editing active-site pocket were substituted between the
      archaeal/eukaryal and bacterial PheRSs. We prepared Ala-substituted mutants of P.
      horikoshii PheRS for 16 editing-pocket residues, of which 12 are archaea/eukarya
      specific and four are more widely conserved. On the basis of their activities,
      Tyr-adenosine was modeled on the B3/4-domain structure. First, the mutations of
      Leu-202, Ser-211, Asp-234, and Thr-236 made the PheRS incorrectly hydrolyze the
      cognate Phe-tRNA(Phe), indicating that these residues participate in the Tyr
      hydroxy group recognition and are responsible for discrimination against Phe.
      Second, the mutations of Leu-168 and Arg-223, which could interact with the tRNA
      3'-terminal adenosine, reduced Tyr-tRNA(Phe) deacylation activity. Third, the
      mutations of archaea/eukarya-specific Gln-126, Glu-127, Arg-137, and Asn-217,
      which are proximal to the ester bond to be cleaved, also reduced Tyr-tRNA(Phe)
      deacylation activity. In particular, the replacement of Asn-217 abolished the
      activity, revealing its absolute requirement for the catalysis.

PMID- 17003131
TI  - Templated biomineralization on self-assembled protein fibers.
AB  - Biological mineralization of tissues in living organisms relies on proteins that
      preferentially nucleate minerals and control their growth. This process is often
      referred to as "templating," but this term has become generic, denoting various
      proposed mineral-organic interactions including both chemical and structural
      affinities. Here, we present an approach using self-assembled networks of elastin
      and fibronectin fibers, similar to the extracellular matrix. When induced onto
      negatively charged sulfonated polystyrene surfaces, these proteins form fiber
      networks of approximately 10-mum spacing, leaving open regions of disorganized
      protein between them. We introduce an atomic force microscopy-based technique to
      measure the elastic modulus of both structured and disorganized protein before
      and during calcium carbonate mineralization. Mineral-induced thickening and
      stiffening of the protein fibers during early stages of mineralization is clearly
      demonstrated, well before discrete mineral crystals are large enough to image by
      atomic force microscopy. Calcium carbonate stiffens the protein fibers
      selectively without affecting the regions between them, emphasizing interactions
      between the mineral and the organized protein fibers. Late-stage observations by
      optical microscopy and secondary ion mass spectroscopy reveal that Ca is
      concentrated along the protein fibers and that crystals form preferentially on
      the fiber crossings. We demonstrate that organized versus unstructured proteins
      can be assembled mere nanometers apart and probed in identical environments,
      where mineralization is proved to require the structural organization imposed by
      fibrillogenesis of the extracellular matrix.

PMID- 17003132
TI  - Tail-interacting protein TIP47 is a connector between Gag and Env and is required
      for Env incorporation into HIV-1 virions.
AB  - The presence of the envelope glycoprotein Env in HIV-1 virions is essential for
      infectivity. To date, the molecular mechanism by which Env is packaged into
      virions has been largely unknown. Here, we show that TIP47 (tail-interacting
      protein of 47 kDa), which has been shown to interact with Env, also binds the MA
      (matrix) domain of HIV-1 Gag protein and that these three proteins form a ternary
      complex. Mutations in Gag that abrogate interaction with TIP47 inhibit Env
      incorporation and virion infectivity as well as colocalization between Gag and
      Env. We also show that TIP47 silencing impairs Env incorporation and infectivity
      and abolishes coimmunoprecipitation of Gag with Env. In contrast, overexpression
      of TIP47 increases Env packaging. Last, we demonstrate that TIP47 can interact
      simultaneously with Env and Gag. Taken together, our results show that TIP47 is a
      cellular cofactor that plays an essential role in Env incorporation, allowing the
      encounter and the physical association between HIV-1 Gag and Env proteins during
      the viral assembly process.

PMID- 17003133
TI  - Transaldolase is essential for maintenance of the mitochondrial transmembrane
      potential and fertility of spermatozoa.
AB  - Fertility of spermatozoa depends on maintenance of the mitochondrial
      transmembrane potential (Deltapsi(m)), which is generated by the electron
      transport chain and regulated by an oxidation-reduction equilibrium of reactive
      oxygen intermediates, pyridine nucleotides, and glutathione (GSH). Here, we
      report that male mice lacking transaldolase (TAL)(-/-) are sterile because of
      defective forward motility. TAL(-/-) spermatozoa show loss of Deltapsi(m) and
      mitochondrial membrane integrity because of diminished NADPH, NADH, and GSH.
      Mitochondria constitute major Ca(2+) stores; thus, diminished mitochondrial mass
      accounts for reduced Ca(2+) fluxing, defective forward motility, and infertility.
      Reduced forward progression of TAL-deficient spermatozoa is associated with
      diminished mitochondrial reactive oxygen intermediate production and Ca(2+)
      levels, intracellular acidosis, and compensatory down-regulation of carbonic
      anhydrase IV and overexpression of CD38 and gamma-glutamyl transferase.
      Microarray analyses of gene expression in the testis, caput, and cauda
      epididymidis of TAL(+/+), TAL(+/-), and TAL(-/-) littermates confirmed a dominant
      impact of TAL deficiency on late stages of sperm-cell development, affecting the
      electron-transport chain and GSH metabolism. Stimulation of de novo GSH synthesis
      by oral N-acetyl-cysteine normalized the low fertility rate of TAL(+/-) males
      without affecting the sterility of TAL(-/-) males. Whereas TAL(-/-) sperm failed
      to fertilize TAL(+/+) oocytes in vitro, sterility of TAL(-/-) sperm was
      circumvented by intracytoplasmic sperm injection, indicating that TAL deficiency
      influenced the structure and function of mitochondria without compromising the
      nucleus and DNA integrity. Collectively, these data reveal an essential role of
      TAL in sperm-cell mitochondrial function and, thus, male fertility.

PMID- 17003135
TI  - Genomic analysis of the hierarchical structure of regulatory networks.
AB  - A fundamental question in biology is how the cell uses transcription factors
      (TFs) to coordinate the expression of thousands of genes in response to various
      stimuli. The relationships between TFs and their target genes can be modeled in
      terms of directed regulatory networks. These relationships, in turn, can be
      readily compared with commonplace "chain-of-command" structures in social
      networks, which have characteristic hierarchical layouts. Here, we develop
      algorithms for identifying generalized hierarchies (allowing for various loop
      structures) and use these approaches to illuminate extensive pyramid-shaped
      hierarchical structures existing in the regulatory networks of representative
      prokaryotes (Escherichia coli) and eukaryotes (Saccharomyces cerevisiae), with
      most TFs at the bottom levels and only a few master TFs on top. These masters are
      situated near the center of the protein-protein interaction network, a different
      type of network from the regulatory one, and they receive most of the input for
      the whole regulatory hierarchy through protein interactions. Moreover, they have
      maximal influence over other genes, in terms of affecting expression-level
      changes. Surprisingly, however, TFs at the bottom of the regulatory hierarchy are
      more essential to the viability of the cell. Finally, one might think master TFs
      achieve their wide influence through directly regulating many targets, but TFs
      with most direct targets are in the middle of the hierarchy. We find, in fact,
      that these midlevel TFs are "control bottlenecks" in the hierarchy, and this
      great degree of control for "middle managers" has parallels in efficient social
      structures in various corporate and governmental settings.

PMID- 17003134
TI  - The role of Pax-6 in lens regeneration.
AB  - Pax-6 is a master regulator of eye development and is expressed in the dorsal and
      ventral iris during newt lens regeneration. We show that expression of Pax-6
      during newt lens regeneration coincides with cell proliferation. By knocking down
      expression of Pax-6 via treatment with morpholinos, we found that proliferation
      of iris pigment epithelial cells was dramatically reduced both in vitro and in
      vivo, and, as a result, lens regeneration was significantly retarded. However,
      induction of dedifferentiation in the dorsal iris was not inhibited. Pax-6
      knockdown early in lens regeneration resulted in inhibition of crystallin
      expression and retardation of lens fiber induction. Once crystallin expression
      and differentiation of lens fibers has ensued, however, loss of function of Pax-6
      did not affect crystallin expression and lens fiber maintenance, even though the
      effects on proliferation persisted. These results conclusively show that Pax-6 is
      associated with distinct early events during lens regeneration, namely control of
      cell proliferation and subsequent lens fiber differentiation.

PMID- 17003136
TI  - Reliving history and renewing the health care reform debate.

PMID- 17003137
TI  - Short-term impacts of coverage loss in a Medicaid population: early results from
      a prospective cohort study of the Oregon Health Plan.
AB  - PURPOSE: Medicaid programs in all 50 states recently implemented cost-saving
      strategies, including benefit reductions, cost sharing, and tightened
      administrative rules. These changes resulted in loss of insurance coverage for
      thousands of low-income adults nationwide. In this study we assessed the
      immediate impacts of disrupted and lost Medicaid coverage on adults enrolled in
      the Oregon Health Plan (OHP) when program changes were implemented. METHODS: Data
      come from baseline survey results of a prospective cohort study designed to
      assess the impacts of OHP changes on adult beneficiaries. We used bivariate and
      multivariate analyses to examine the effects of disrupted and lost insurance
      coverage on unmet health care needs, utilization, and medical debt occurring in
      the first 10 months after OHP changes were implemented. RESULTS: After OHP
      changes were implemented, 31% of enrolled adults reported losing coverage, and
      another 15% reported disrupted coverage. Controlling for demographic
      characteristics, income, and health status, those with disrupted coverage were
      less likely to have a primary care visit (odds ratio [OR] = .66; P <.05) and more
      likely to report unmet health care needs (OR = 1.85; P <.01) and medical debt (OR
      = 1.99; P <.01) when compared with those continuously insured. Those who lost
      coverage were less likely to have a primary care visit (OR = 0.18; P <.01) and
      more likely to report unmet health care needs (OR = 5.55; P <.01), unmet
      medication needs (OR = 2.05; P <01), and medical debt (OR = 3.06; P <.01) than
      those continuously insured. CONCLUSIONS: Medicaid program changes that increase
      cost sharing and limit enrollment have significant negative impacts on health
      care access and utilization among Medicaid beneficiaries; these impacts occur
      rapidly, within the first 10 months after changes.

PMID- 17003138
TI  - Primary care physicians' perceptions of the effect of insurance status on
      clinical decision making.
AB  - PURPOSE: Americans who do not have health insurance receive fewer health services
      and have poorer health status than those who have insurance. To better understand
      this disparity, in this study we characterize primary care physician's
      perceptions of what effect, if any, patients' insurance status has on their
      clinical decision making during office visits. METHODS: Twenty-five physician
      members of CAPRICORN, a primary care practice-based research network in
      metropolitan Washington, DC, completed a brief paper-card survey instrument
      immediately after each patient encounter during 2 half-day office sessions.
      Participants saw patients in their usual manner and were given no additional
      information about their patients or their insurance. RESULTS: Eighty-eight
      percent of participating physicians reported making at least 1 change in clinical
      management as a result of a patient's insurance status. They reported altering
      their management during 99 of 409 patient encounters (24.2%). There was a
      significant difference in the percentage of visits that involved a change in
      management for privately insured, publicly insured, and uninsured patients
      (18.7%, 29.5%, and 43.5% respectively, P = .01). Physicians reported discussing
      insurance issues with patients during 62.6% of visits during which they made a
      change in management based on insurance status. CONCLUSION: Physicians
      incorporate their patients' insurance status into their clinical decision making
      and acknowledge they frequently alter their clinical management as a result.
      Additional research is needed to understand the effect of these changes on
      patient health and to assist both physicians and patients in enhancing the
      quality of care delivered within the constraints of the current insurance system.

PMID- 17003139
TI  - Mandatory reporting of elder abuse: between a rock and a hard place.
AB  - PURPOSE: Despite mandated reporting laws that require physicians to report elder
      abuse, physicians have low rates of reporting. The purpose of this study was to
      identify physician's perspectives on mandated reporting of elder abuse. METHODS:
      Individual, semistructured interviews were conducted with 20 primary care
      physicians practicing in a variety of settings and caring for a diverse patient
      population in the Los Angeles area. Interviewers collected information on
      physicians' perspectives about factors that may influence physicians' likelihood
      to report elder abuse. The interviews were recorded and transcribed verbatim.
      Transcripts were analyzed using a grounded theory approach based on the constant
      comparative method and the emergence of the core category of paradox to best
      account for the most problematic elder abuse situations faced by physicians.
      RESULTS: During the interviews 3 paradoxes were expressed by physicians about the
      mandatory reporting of elder abuse. Specifically, mandatory reporting was related
      to both perceptions of increases and decreases in physician-patient rapport,
      patient quality of life, and physician control or ability to decide what is in
      the best interest of the patient. These paradoxes appear to be primarily hidden
      or unconscious, yet they influence the conscious decision process of whether to
      report. CONCLUSIONS: Primary care physicians appear to be subject to paradoxes of
      reporting that contribute to the underreporting of elder abuse. These paradoxes
      and alternative modes of managing paradoxes are important and should be addressed
      in educational and training programs for physicians, and systematic evaluation of
      these issues may help to inform future legislation in this area. Further studies
      are needed to assess the generalizability of these findings to other groups of
      clinicians.

PMID- 17003140
TI  - Excess mortality caused by medical injury.
AB  - PURPOSE: We wanted to estimate excess risk of in-hospital mortality associated
      with medical injuries identified using an injury surveillance system, after
      controlling for risk of death resulting from comorbidities. METHODS: The
      Wisconsin Medical Injuries Prevention Program (WMIPP) screening criteria were
      used to identify medical injuries, defined as "any untoward harm associated with
      a therapeutic or diagnostic healthcare intervention," among discharge diagnoses
      for all 562,317 patients discharged from 134 acute care hospitals in Wisconsin in
      2002. We then derived estimates for crude and adjusted relative risk of in
      hospital mortality associated with the presence of a medical injury diagnosis.
      Logistic regression adjusted for baseline risk of mortality using a comorbidity
      index, age, sex, Diagnosis Related Groups, hospital characteristics, and
      clustering within hospital. RESULTS: There were 77,666 discharges that met WMIPP
      criteria for at least 1 medical injury (13.8%). Crude risk ratios for death
      ranged from 1.27 to 2.4 for those with medical injuries within 1 of 4 categories:
      drugs/biologics; devices, implants, and grafts; procedures; and radiation. After
      adjustment, estimates of excess mortality decreased, and significance persisted
      only for injuries related to procedures (39%; 95% confidence interval [CI], 28%
      52%) and devices, implants, and grafts (16%; 95% CI, 3%-30%). CONCLUSIONS:
      Estimates of excess mortality that do not account for baseline mortality risk may
      be exaggerated. Findings have implications for the care family physicians provide
      in the hospital and for the advice they give their patients who are concerned
      about the risks of hospitalization.

PMID- 17003142
TI  - Associations between night sweats and other sleep disturbances: An OKPRN study.
AB  - PURPOSE: Surprisingly little is known about the causes and implications of night
      sweats. This study was designed to clarify further the associations between night
      sweats and sleep-related symptoms. METHODS: We undertook a cross-sectional study
      of consecutive adult patients seen in 10 primary care physicians' offices. Data
      were collected and transmitted by a personal digital assistant. Information
      included demographic variables; height, weight, and blood pressure; occurrence of
      a variety of sleep-related symptoms; and occurrence and severity of night sweats,
      day sweats, and hot flashes in the past month. For women, information about
      menstrual status was also obtained. RESULTS: Thirty-four percent of the 363
      patients interviewed reported night sweats, one half of whom reported saturating
      their bedclothes. In the multivariate model, night sweats were associated with
      daytime tiredness (OR = 1.99; 95% CI, 1.12-3.53), waking up with a bitter taste
      in the mouth (OR = 1.94; 95% CI, 1.19-3.18), legs jerking during sleep (OR =
      1.78; 95% CI, 1.05-3.00), and awakening with pain in the night (OR = 1.87; 95%
      CI, 1.16-2.99). CONCLUSIONS: Night sweats are associated with several sleep
      symptoms. Both night sweats and sleep disturbances are commonly experienced by
      adult primary care patients. When their patients report night sweats, clinicians
      should consider asking about sleep quality and sleep-related symptoms.

PMID- 17003141
TI  - Psychological distress and multimorbidity in primary care.
AB  - PURPOSE: Psychological distress may decrease adherence to medical treatments and
      lead to poorer health outcomes of chronic diseases. The aim of this study was to
      evaluate the relationship between psychological distress and multimorbidity among
      patients seen in family practice after controlling for potential confounding
      variables and taking into account the severity of diseases. METHODS: We evaluated
      238 patients to construct quintiles of increasing multimorbidity based on the
      Cumulative Illness Rating Scale (CIRS), which is a comprehensive multimorbidity
      index that takes into account disease severity. Patients completed a psychiatric
      symptom questionnaire as a measurement of their psychological distress. In the
      first model of logistic regression analyses, we used the counted number of
      chronic diseases as the independent variable. In subsequent models, we used the
      quintiles of CIRS. RESULTS: After adjusting for confounding factors,
      multimorbidity measured by a simple count of chronic diseases was not related to
      psychological distress (OR, 1.12; 95% CI, 0.97-1.29; P = .188), whereas
      multimorbidity measured by the CIRS remained significantly associated (OR, 1.67;
      95% CI, 1.19-2.37; P = .002). The estimate risk of psychological distress by
      quintile of CIRS was as follows: Q1/2 = 1.0; Q3 = OR, 1.72; 95% CI, 0.53-5.86; Q4
      = OR, 2.99; 95% CI, 1.01-9.74; Q5 = OR, 4.67; 95% CI, 1.61-15.16. CONCLUSIONS:
      Psychological distress increased with multimorbidity when we accounted for
      disease severity. Clinicians should be aware of the possible presence of
      psychological distress, which can further complicate the comprehensive management
      of these complex patients.

PMID- 17003143
TI  - Evidence of nephropathy and peripheral neuropathy in US adults with undiagnosed
      diabetes.
AB  - PURPOSE: Nearly one third of diabetes cases in the United States is undiagnosed,
      with mounting evidence that complications accrue even before clinical diagnosis.
      We wanted to determine whether persons with undiagnosed diabetes have signs of
      nephropathy and peripheral neuropathy. METHODS: We examined the prevalence of
      positive screening tests for nephropathy and peripheral neuropathy in adults aged
      > or = 40 years with undiagnosed diabetes using secondary analysis of survey and
      examination data from the population-based United States National Health and
      Nutrition Examination Survey 1999-2002. We defined a positive screening test for
      nephropathy as a spot urine albumin-creatinine ratio > 30.0 mg/g, representing at
      least microalbuminuria. We defined > or = 1 insensate area on Semmes-Weinstein
      monofilament testing as a positive finding for neuropathy. Undiagnosed diabetes
      was defined as a combination of no history of diagnosed diabetes and a measured
      fasting glucose > or = 126 mg/dL. We used SUDAAN for chi2 and regression
      analyses. RESULTS: The prevalence of a positive test when screening for
      nephropathy among those with undiagnosed diabetes was 26.5% compared with 7.1% in
      those with no diabetes (chi2, P <.01). After adjusting for age and diagnosed or
      undiagnosed hypertension, the association of undiagnosed diabetes with
      nephropathy persisted (odds ratio = 2.35; 95% confidence interval, 1.38-4.01).
      For peripheral neuropathy, 21.5% with undiagnosed diabetes had positive screening
      tests compared with 10.1% with no diabetes (chi2, P <.01); however, this effect
      was not significant after adjustment for age. There was no significant difference
      in positive screening tests for nephropathy or neuropathy when comparing those
      with undiagnosed and diagnosed diabetes. CONCLUSIONS: A significant proportion of
      adults with undiagnosed diabetes have signs of nephropathy and peripheral
      neuropathy. These findings may influence policies about early screening for
      diabetes.

PMID- 17003144
TI  - US men discussing prostate-specific antigen tests with a physician.
AB  - PURPOSE: Informed decision making is recommended for prostate cancer screening. I
      wanted to examine demographic and screening-related factors associated with men's
      discussion of the advantages and disadvantages of prostate-specific antigen (PSA)
      tests with their physicians. METHODS: I used data from 2,184 men aged 50 years
      and older who reported a screening prostate-specific antigen (PSA) test in the
      2000 National Health Interview Survey cancer control supplement. The dependent
      variable was discussion of the advantages and disadvantages of the test before it
      was conducted. RESULTS: Sixty-three percent of tested men reported a discussion
      in relation to their most recent PSA test. Discussion was more common for African
      American men and those with a usual source of care, and when the physician
      initiated the testing. CONCLUSIONS: Characteristics of the patient-physician
      relationship were more central to the discussion of risks and benefits than were
      patient attributes. Future research should examine what role practice setting and
      the physician-patient relationship play in a discussion of PSA testing and how to
      facilitate active involvement of patients in decision making.

PMID- 17003145
TI  - NIH funding in family medicine: an analysis of 2003 awards.
AB  - PURPOSE: We wanted to analyze National Institutes of Health (NIH) awards to
      departments of family medicine. METHODS: We obtained the list of NIH awards to
      departments of family medicine in 2003, and collected additional information from
      the Internet regarding each principal investigator (PI), including whether he or
      she worked primarily in a core (central) organizational component within a family
      medicine department. RESULTS: One hundred forty-nine NIH awards were granted to
      45 departments of family medicine, for a total of 60,085,000 dollars. Of 146
      awards with a designated PI, approximately two thirds of awards (89, 61%) and
      awarded dollars (39,850,000 dollars, 70%) went to PIs who were either not full
      time family medicine faculty primarily working in family medicine departments, or
      they were not working in core family medicine organizational components. Few
      awards to physician PIs in these non-core areas were to family physicians (4 of
      37, 11%), whereas most awards to physician PIs in core family medicine areas went
      to family physicians (40 of 45, 89%). In contrast, most K awards (research career
      programs) went to PIs in core areas (19 of 23, 83%), and most to family
      physicians (17 of 23, 74%). Nationally, only 17 R01 awards (research project,
      traditional) went to family physicians. CONCLUSIONS: Most NIH awards to family
      medicine departments went to PIs in noncore organizational components, where most
      physician PIs were not family physicians. Family medicine departments interested
      in increasing NIH funding may want to consider 4 models that appear to exist:
      individual faculty in core departmental components, K awards, core faculty also
      working in university-wide organizational components that provide research
      infrastructure, and integrating noncore administrative components into the
      department.

PMID- 17003146
TI  - Creating innovative research designs: the 10-year Methodological Think Tank case
      study.
AB  - PURPOSE: Addressing important but complex research questions often necessitates
      the creation of innovative mixed methods designs. This report describes an
      approach to developing research designs for studying important but
      methodologically challenging research questions. METHODS: The Methodological
      Think Tank has been held annually in conjunction with the Primary Care Research
      Methods and Statistics Conference in San Antonio since 1994. A group of 3 to 4
      methodologists with expertise balanced between quantitative and qualitative
      backgrounds is invited by the think tank coordinators to serve on a 2-day think
      tank to discuss a research question selected from those submitted in response to
      a call for proposals. During the first half-day, these experts explore the
      content area with the investigator, often challenging beliefs and assumptions.
      During the second half-day, the think tank participants systematically prune
      potential approaches until a desirable research method is identified. RESULTS: To
      date, the most recent 7 think tanks have produced fundable research designs, with
      1 being funded by a K award and 4 by R01 grants. All participating investigators
      attributed much of their success to think tank participation. Lessons learned
      include (1) the importance of careful selection of participating methodologists,
      (2) all think tank communities of inquiry must go through 4 stages of development
      from pseudocommunity to community, and (3) the critical importance of listening
      by the investigator. CONCLUSION: Researchers and academic departments could use
      this process locally to develop innovative research designs.

PMID- 17003147
TI  - General medical practitioners need to be aware of the theories on which our work
      depend.
AB  - When general practitioners and family physicians listen, reflect, and diagnose,
      we use 3 different theories of knowledge. This essay explores these theories to
      highlight an approach to clinical practice, inquiry, and learning that can do
      justice to the complex and uncertain world we experience. The following points
      are made: (1) A variety of approaches to research and audit are needed to
      illuminate the richness of experience witnessed by general medical practitioners.
      (2) Evidence about the past cannot predict the future except in simple, short
      term, or slowly changing situations. (3) We consciously or unconsciously weave
      together evidence generated through 3 fundamental theories of knowledge, termed
      postpositivism, critical theory, and constructivism, to make sense of everyday
      experience. We call it listening, reflecting, and diagnosing. (4) These 3
      fundamental theories of knowledge highlight different aspects within a world that
      is more complex, integrated, and changing than any single theory can reveal on
      its own; they frame what we see and how we act in everyday situations. (5) Moving
      appropriately between these different theories helps us to see a fuller picture
      and provides a framework for improving our skills as clinicians, researchers, and
      learners. (6) Narrative unity offers a way to bring together different kinds of
      evidence to understand the overall health of patients and of communities;
      evidence of all kinds provides discrete snapshots of more complex stories in
      evolution. (7) We need to understand these issues so we can create an agenda for
      clinical practice, inquiry, and learning appropriate to our discipline.

PMID- 17003148
TI  - Family medicine's identity: being generalists in a specialist culture?
AB  - Family medicine has been in conflict about whether it is a specialty or a
      generalist discipline. Although for a time the family was offered as a solution
      to family medicine being marginalized in biomedicine, a more biomedical focus
      prevailed. As a result, the practice of family medicine came more to resemble the
      world of biomedicine despite an insistence on the discipline's distinctiveness.
      Ways to avoid identity pitfalls in the future might be to seek solutions that do
      not promise to solve our identity problem once and for all, to refrain from
      adopting generalized slogans that do not encourage critical thinking, to practice
      what we preach, to accept that specialization is part of the American cultural
      ethos, and to embrace reflective practice.

PMID- 17003149
TI  - Si, doctora.
AB  - Experience with seeing Latino patients at a community health center has taught a
      family physician that the patient's response, "Si, doctora [Yes, doctor]" can
      have multiple meanings. Patients might say "yes" during consultations to avoid
      conflict or to defer to the more powerful doctor. The clinician's understanding
      had to move to deeper levels when a visiting Ecuadorian friend learning English
      used "yes" multiple times in conversation, but not as an indicator of agreement
      or even comprehension. The family doctor realized that she could not assume what
      the patient implies by this simple expression. The apparent agreement of "yes"
      requires more. When a patient says, "Si, doctora," the doctor must probe with
      more questions and listen hard to the answers.

PMID- 17003150
TI  - Title VII: our loss, their pain.

PMID- 17003151
TI  - Primary care research in Canada and the United States.

PMID- 17003152
TI  - June happenings: significant for specialty?

PMID- 17003153
TI  - MC-FP Early Start, EM/FM combined program.

PMID- 17003154
TI  - STFM New Partners Initiative: a productive first year!

PMID- 17003155
TI  - Successful turnaround of a university-owned, community-based, multidisciplinary
      practice network.
AB  - PURPOSE: The University of Utah purchased a 100-clinician, 9-practice multi
      specialty primary care network in 1998. The university projected the network to
      earn a profit the first year of its ownership in a market with growing
      capitation; however, capitation declined and the network incurred up to a 21
      million dollars operating loss per year. This case study describes the financial
      turnaround of the network. METHODS: In 2001, the university reconfigured the
      practices for a fee-for-service environment while preserving the group's
      multidisciplinary clinical and ancillary services. Changes included
      reorganization under the existing University of Utah Hospitals and Clinics
      system, new governance and leadership, closure of practices, creation of a
      billing office, new financial reporting, implementation of electronic health
      records, revision of physician compensation, capture of referrals, leadership and
      staff training, and practice reengineering. RESULTS: The network as a whole
      became profitable in 2004-2005. Its primary care component is projected to become
      profitable in 2 to 3 years. The network is opening new sites strategically
      important to the health system. CONCLUSIONS: This turnaround required commitment
      from senior university leaders, management with knowledge of primary care
      practice, retention of ancillary revenues, and management and business services
      specific to the network with support from other units within the university.
      Culture change within the group was essential. Our experience suggests that an
      academic health center can successfully operate a primary care network by
      attending to the unique needs of this challenging business. Doing so can
      strengthen the institution's overall financial and clinical performance and
      provide an important setting for teaching and research.

PMID- 17003156
TI  - The Utah primary care experience.

PMID- 17003158
TI  - The Health Commons and care of New Mexico's uninsured.
AB  - PURPOSE: A seamless system of social, behavioral, and medical services for the
      uninsured was created to address the social determinants of disease, reduce
      health disparities, and foster local economic development in 2 inner-city
      neighborhoods and 2 rural counties in New Mexico. METHODS: Our family medicine
      department helped urban and rural communities that had large uninsured, minority
      populations create Health Commons models. These models of care are characterized
      by health planning shared by community stakeholders; 1-stop shopping for medical,
      behavioral, and social services; employment of community health workers bridging
      the clinic and the community; and job creation. RESULTS: Outcomes of the Health
      Commons included creation of a Web-based assignment of uninsured emergency
      department patients to primary care homes, reducing return visits by 31%;
      creation of a Web-based interface allowing partner organizations with
      incompatible information systems to share medical information; and creation of a
      statewide telephone Health Advice Line offering rural and urban uninsured
      individuals access to health and social service information and referrals 24
      hours a day, 7 days a week. The Health Commons created jobs and has been
      sustained by attracting local investment and external public and private funding
      for its products. Our department's role in developing the Health Commons helped
      the academic health center (AHC) form mutually beneficial community partnerships
      with surrounding and distant urban and rural communities. CONCLUSIONS: Broad
      stakeholder participation built trust and investment in the Health Commons,
      expanding services for the uninsured. This participation also fostered marketable
      innovations applicable to all Health Commons' sites. Family medicine can promote
      the Health Commons as a venue for linking complementary strengths of the AHC and
      the community, while addressing the unique needs of each. Overall, our experience
      suggests that family medicine can play a leadership role in building
      collaborative approaches to seemingly intractable health problems among the
      uninsured, benefiting not only the community, but also the AHC.

PMID- 17003157
TI  - Shaping the future of academic health centers: the potential contributions of
      departments of family medicine.
AB  - Academic health centers (AHCs) must change dramatically to meet the changing
      needs of patients and society, but how to do this remains unclear. The purpose of
      this supplement is to describe ways in which departments of family medicine can
      play leadership roles in helping AHCs evolve. This overview provides background
      for case studies and commentaries about the contribution of departments of family
      medicine in 5 areas: (1) ambulatory and primary care, (2) indigent care, (3)
      education in community and international settings, (4) workforce policy and
      practice, and (5) translational research. The common theme is a revitalization of
      the relationship between AHCs and the communities they serve across all missions.
      Family medicine leadership can provide dramatic organizational improvement in
      primary and ambulatory care networks and foster opportunities for leadership by
      AHCs in improving the health of the population. Departments of family medicine
      can also play a leading role in developing new partnerships with community-based
      organizations, managing the care of the indigent, and developing new curricula in
      community and international settings. Finally, family medicine departments and
      their faculty have a central role in helping AHCs respond to workforce needs and
      in developing translational research that emphasizes the health of the population
      and effectiveness of care. AHCs are a public good that must now evolve
      substantially to meet the needs of patients and society. By pushing for
      substantial change, by helping to reinvigorate the relationship between AHCs and
      the communities they serve, and by emphasizing fundamental innovation in clinical
      care, teaching, and research, family medicine can help lead the renewal of the
      AHC.

PMID- 17003159
TI  - Managing the uninsured with a community network.

PMID- 17003160
TI  - Capturing medical students' idealism.
AB  - PURPOSE: Students' idealism and desire to work with underserved populations
      decline as they progress from preclinical training through clerkships and
      residency. With an increasingly diverse population and increasing health
      disparities, academic health centers need to incorporate changes in their
      curricula to train socially responsible and idealistic physicians. International
      electives can provide valuable learning experiences to help achieve these goals.
      METHODS: Sixty-six preclinical medical students at the University of Texas
      Medical Branch participated in an international elective from 1997 to 2005. After
      1 week of didactics, they spent 3 weeks as part of a multidisciplinary medical
      team in rural Nicaragua. Postelective questionnaires were administered. From
      students' responses, we identified common learning themes and grouped them under
      the categories of attitudes, awareness, and skills. Limitations included a self
      selection bias, lack of a control group, and limited follow-up. RESULTS: After
      the elective, students had an increased interest in volunteerism, humanitarian
      efforts, and working with underserved populations both in the United States and
      abroad, as well as more compassion toward the underserved. Students also reported
      a heightened awareness of social determinants of health and public health, and a
      broadened global perspective, as well as increased self-awareness. CONCLUSIONS:
      Our findings illustrate that a well-structured, mentored experience in
      international health can have a positive impact on preclinical students'
      attitudes, including their compassion, volunteerism, and interest in serving
      under-served populations, all measures of idealism.

PMID- 17003161
TI  - Getting the most out of medical students' global health experiences.

PMID- 17003162
TI  - A workforce analysis informing medical school expansion, admissions, support for
      primary care, curriculum, and research.
AB  - PURPOSE: This case study describes the findings of a physician workforce analysis
      and how an institution is using these findings to address the decreasing
      proportion of medical students choosing primary care careers. METHODS: A
      University of Washington School of Medicine committee commissioned an analysis of
      the American Medical Association Physician Masterfile. The analysis examined
      physician-to-population ratios, rural-urban geographic distribution, physician
      demographics, and physician graduation from the university or one of its
      affiliated residency programs for graduates of allopathic medical schools and
      residencies at the county level in the 5 states in the WWAMI partnership
      (Washington, Wyoming, Alaska, Montana, and Idaho). RESULTS: The analysis found
      that in 2005, the 5 WWAMI states ranked at the bottom of US states in the number
      of publicly supported medical school and residency slots per capita. Although
      physician-to-population ratios were comparable to those in the rest of the
      country, the 5 WWAMI states imported most of their physicians, including family
      physicians, approximately 70% of whom came from other medical schools or
      residency programs. Family physicians were the only specialty distributed across
      the population gradient from urban to isolated rural areas. The workforce
      analysis is informing planning for medical school expansion, admissions, support
      for primary care, curriculum, and research at an institution with a clear mission
      that includes training the health workforce for its region. CONCLUSIONS: The
      analysis has wide potential applicability, but it has special relevance for
      primary care and has been particularly useful in making the case for supporting
      primary care education in the WWAMI region.

PMID- 17003163
TI  - Social accountability in theory and practice.

PMID- 17003164
TI  - The Michigan Clinical Research Collaboratory: following the NIH Roadmap to the
      community.
AB  - PURPOSE: This case study describes a successful National Institutes of Health
      (NIH) Roadmap application that has created a new and innovative translational
      science partnership at the University of Michigan. METHODS: We describe the
      institution within which the grant application was developed, the role played by
      the Department of Family Medicine, the role of prior successes in translational
      and community-based research, the associated infrastructure development, the
      application development process, and some features of the final project. RESULTS:
      A partnership among 2 clinical and research centers of excellence at the
      University of Michigan, 3 practice-based research networks, and a clinical
      research center was created as the platform to support an NIH Roadmap. The result
      was a funded 3.3 million dollar, 3-year project supporting the creation of the
      Michigan Clinical Research Collaboratory (MCRC), a research infrastructure that
      will support the design, conduct, and dissemination of community-based clinical
      translation research. The MCRC depends to a considerable degree on the
      experience, expertise, and infrastructure in community-based translational
      research of the Department of Family Medicine. CONCLUSIONS: The successful
      funding of the MCRC grant will support influential translational research
      programs of high impact and visibility that would not otherwise have occurred.
      The MCRC grant is an acknowledgment of the important research to be done in the
      community, the critical nature of infrastructure investment and prior work in
      competing successfully for such funding, and the personnel and information
      technology investments required for success. Collaboration between practice-based
      family medicine investigators and traditional clinical investigators at the
      University of Michigan has led to successful competition for an NIH Roadmap
      grant, which has led in turn to greater institutional recognition for the
      importance and legitimacy of community-based translational research.

PMID- 17003165
TI  - The role of academic health centers in improving health.

PMID- 17003167
TI  - In silico prediction of pregnane X receptor activators by machine learning
      approaches.
AB  - Pregnane X receptor (PXR) regulates drug metabolism and is involved in drug-drug
      interactions. Prediction of PXR activators is important for evaluating drug
      metabolism and toxicity. Computational pharmacophore and quantitative structure
      activity relationship models have been developed for predicting PXR activators.
      Because of the structural diversity of PXR activators, more efforts are needed
      for exploring methods applicable to a broader spectrum of compounds. We explored
      three machine learning methods (MLMs) for predicting PXR activators, which were
      trained and tested by using significantly higher number of compounds, 128 PXR
      activators (98 human) and 77 PXR non-activators, than those of previous studies.
      The recursive feature-selection method was used to select molecular descriptors
      relevant to PXR activator prediction, which are consistent with conclusions from
      other computational and structural studies. In a 10-fold cross-validation test,
      our MLM systems correctly predicted 81.2 to 84.0% of PXR activators, 80.8 to
      85.0% of hPXR activators, 61.2 to 70.3% of PXR nonactivators, and 67.7 to 73.6%
      of hPXR nonactivators. Our systems also correctly predicted 73.3 to 86.7% of 15
      newly published hPXR activators. MLMs seem to be useful for predicting PXR
      activators and for providing clues to physicochemical features of PXR activation.

PMID- 17003168
TI  - Synovial fluid metabolites in osteonecrosis.
AB  - OBJECTIVES: Osteonecrosis of the femoral head results from interruption of the
      vascular supply and eventual death of the cellular portion of bone. Effective
      methods of monitoring response to treatment are needed. Our aim was to evaluate
      synovial fluid metabolites, glucose and lactate, as biomarkers in a canine model
      of osteonecrosis. METHODS: Osteonecrosis was cryosurgically induced in the right
      femoral head while the left hip served as control (n = 31). Animals either
      underwent no further intervention (n = 10), vascular endothelial growth factor
      (VEGF) injections (n = 4), placement of a vascularized bone graft (n = 6), a
      combination of VEGF microinjection and vascularized graft placement (n = 5), or
      treatment with daily oral alendronate (n = 6). After 12 weeks, synovial fluid
      from each hip joint was obtained for glucose and lactate concentrations. RESULTS:
      Joints with surgically induced osteonecrosis demonstrated decreased synovial
      fluid concentrations of glucose (P < 0.05) and elevated concentrations of lactate
      (P < 0.05) relative to contralateral control hips. When animals were treated with
      VEGF, the vascularized graft placement, or vascularized graft and VEGF, there
      were no differences in the synovial fluid concentrations of these metabolites
      between cryoablated and control hips. In contrast, alendronate did not normalize
      the concentration of these synovial fluid metabolites in the cryoablated hips.
      CONCLUSIONS: Osteonecrosis of the femoral head is associated with alterations in
      synovial fluid glucose and lactate, reflecting anaerobic metabolism. These
      metabolites may serve as useful tools for monitoring response to
      revascularization therapies.

PMID- 17003170
TI  - What kills patients with rheumatoid arthritis?

PMID- 17003171
TI  - Contribution of MHC class I region to genetic susceptibility for giant cell
      arteritis.
AB  - OBJECTIVE: The aim of this study was to assess the potential contribution of HLA
      class I MICA and HLA-B gene polymorphisms towards the pathogenesis of giant cell
      arteritis (GCA). METHODS: Ninety-eight biopsy-proven GCA patients and 225
      ethnically matched controls from Lugo, Northwest Spain, were genotyped for the
      MICA-TM microsatellite polymorphism using a polymerase chain reaction (PCR)-based
      method. Genotyping of HLA-B was performed using PCR and detection with a reverse
      sequence-specific oligonucleotide (SSO) probes system. RESULTS: A significant
      difference in the distribution of the alleles of MICA between patient and control
      groups (P = 0.005) was found. This was due to an increased frequency of the MICA
      A5 allele in GCA patients compared with controls (26 vs 13.6%; P = 0.0001; P(C) =
      0.0005; OR 2.2, 95% CI 1.4-3.4). In addition, the HLA-B*15 allele showed a higher
      frequency in GCA patients compared with controls (P = 0.004; P(C) = 0.04; OR 2.7,
      95% CI 1.3-5.7). Interestingly, the association observed with the MICA A5 allele
      seems to be independent of linkage disequilibrium with HLA-B, as well as
      independent of that previously described with HLA-DRB1*04. Remarkably,
      simultaneous presence of MICA A5 and HLA-B*15 or HLA-DRB1*04 genetic markers
      leads to an increase in the OR obtained for each individual genetic marker (MICA
      A5 + B*15 OR 3.2; MICA A5 + DRB1*04 OR 5.8). CONCLUSIONS: Our results provide the
      first evidence that the MICA and HLA-B genes are independently associated with
      the genetic susceptibility to GCA, and suggest that several genes within the MHC
      might have independent effects in the susceptibility to this systemic vasculitis.

PMID- 17003172
TI  - Comparison of musculoskeletal ultrasound practices of a rheumatologist and a
      radiologist.
AB  - OBJECTIVE: There is considerable debate regarding the role of the rheumatologist
      ultrasonographer and how this development will impact on musculoskeletal
      ultrasound (MSUS) performed by radiologists. We compared the MSUS practices of a
      rheumatologist and a radiologist working within the same National Health Service
      Trust. METHODS: A retrospective review of MSUS reports of consecutive scans
      performed by a consultant rheumatologist with a special interest in MSUS and a
      consultant musculoskeletal radiologist. Reports were analysed for referring
      specialties, indications for MSUS, joint regions scanned, MSUS findings,
      frequency with which patients were referred for injection and how often injection
      was performed. RESULTS: A total of 170 patients were referred to the
      rheumatologist for MSUS of 282 joint regions (91% referred by rheumatologists).
      Of those, 84 (49%) patients had MSUS examination of more than one joint region,
      with up to five regions scanned per sitting. One hundred patients were referred
      to the radiologist for MSUS of 111 joint regions (49% referred by orthopaedic
      surgeons). The most frequently requested primary indication for MSUS performed by
      the rheumatologist was detection of synovitis [74 (44%) patients] while MSUS
      performed by the radiologist was most frequently for assessment for major
      structural changes [44 (44%) patients]. The rheumatologist performed MSUS-guided
      injection in 59 of 170 (35%) patients scanned and the radiologist in 13 of 100
      (13%). CONCLUSION: MSUS performed by the rheumatologist was predominantly
      requested by rheumatologists to aid diagnosis of synovial and tendon inflammation
      and to guide injections, while MSUS performed by the radiologist was
      predominantly requested by orthopaedic surgeons to aid diagnosis of structural
      pathology. Curriculums in MSUS designed for rheumatologists may need to place
      appropriate emphasis on the identification of synovial and tendon inflammation,
      and injection guidance.

PMID- 17003173
TI  - Mycophenolate mofetil treatment in resistant myositis.
AB  - OBJECTIVES: To assess the efficacy and tolerability of mycophenolate mofetil
      (MMF) in six patients with myositis refractory to conventional immunosuppressive
      therapy. METHODS: Six patients were identified from hospital notes. All had
      previously failed to respond to other immunosuppressive treatments. Efficacy was
      measured as changes in muscle strength, creatine kinase (CK) levels and
      prednisolone dose. RESULTS: The mean age of the group was 49.8 +/- 9.1 yrs, 6
      (100%) were female and Caucasian. Patients had failed to respond to a median of 3
      (range 1-3) immunosuppressive drugs. They received MMF for a mean of 22.3 +/-
      18.9 months with a mean MMF dose of 1.6 +/- 0.5 g/day. The mean initial
      prednisolone dose was 13.7 +/- 7.7 mg and the mean follow up dose was 8.5 +/- 4.9
      mg/day (P = 0.03). CK levels were reduced from mean 2395 IU/l +/- 1202.8 to 746.6
      +/- 555.8 IU/l (P = 0.03). CONCLUSION: Our data demonstrate that MMF may be
      effective in myositis, previously unresponsive to conventional immunosuppressive
      drugs.

PMID- 17003174
TI  - Ultrasonography in rheumatology: developing its potential in clinical practice
      and research.

PMID- 17003175
TI  - Rates and predictors of herpes zoster in patients with rheumatoid arthritis and
      non-inflammatory musculoskeletal disorders.
AB  - OBJECTIVES: Herpes zoster (HZ) is a common disorder that causes substantial pain
      and morbidity. We examined its rate and predictors in rheumatoid arthritis (RA)
      and non-inflammatory musculoskeletal (MSK) disorders to determine if HZ was
      increased in RA and whether treatment contributed to the risk of HZ. METHODS:
      After excluding patients witzh prior HZ, we assessed 10 614 RA and 1721 MSK
      patients by semi-annual questionnaires during 33 825 patient-years of follow-up.
      Predictors of HZ were determined by Cox regression and expressed as hazard ratios
      (HR) and 95% confidence intervals (CI). RESULTS: The annualized incidence rate
      per 1000 patient-years was 13.2 (95% CI 11.9-14.5) in RA and 14.6 (95% CI 11.2
      18.1) in MSK, and did not differ significantly after adjustment for age and sex.
      HZ was predicted by impaired functional status, as measured by the Health
      Assessment Questionnaire (HAQ), [HR 1.3 (95% CI 1.1-1.5)] and by the use of COX-2
      specific non-steroidal anti-inflammatory drugs (NSAIDs) [HR 1.3 (95% CI 1.1-1.6)]
      in RA and MSK. In multivariable analyses in patients with RA, cyclophosphamide HR
      4.2 (95% CI 1.6-11.5), azathioprine HR 2.0 (1.2-3.3), prednisone HR 1.5 (1.2
      1.8), leflunomide HR 1.4 (1.1-1.8) and COX-2 NSAIDs HR 1.3 (95% CI 1.1-1.6) were
      significant predictors of HZ. CONCLUSION: The incidence of HZ is increased in RA
      and MSK compared with population-based rates. However, the rate of HZ in RA is
      not increased compared with MSK. After adjustment for severity, various
      treatments, but not methotrexate or biologics, were risk factors for HZ.

PMID- 17003177
TI  - Extremity injury in war: a brief history.
AB  - The complex history of treating traumatic injury in Western warfare consistently
      included issues such as proximity to surgical care, the organization of medical
      systems, and the progressive development of technologies and procedures used to
      treat military service members who are injured in battle. Significant advances
      have been made in each of these areas, as evidenced in the changes in medical
      care in conflicts involving US forces. These advances include, among others,
      organized attempts to improve sanitation; panels of surgeons to assess optimal
      surgical approaches; the introduction of triage, wound debridement, and delayed
      wound closure; the development of chemotherapeutics and antibiotics; and
      increasingly more timely treatment. Perhaps the least recognized historical
      contribution to military medical care, however, is the compiled medical
      statistic, which informs bold research and response.

PMID- 17003176
TI  - MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis
      susceptibility.
AB  - OBJECTIVES: Several recent studies have shown that the MHC class III region,
      located telomeric to HLA-DRB1, contains an additional genetic factor that
      predisposes to rheumatoid arthritis (RA). In this study, we investigate whether
      inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III
      region are the second susceptibility gene associated with RA. METHODS: A total of
      154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB
      and the polymorphism -62 of the IkappaBL gene. RESULTS: A significant increase of
      HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%,
      P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401
      (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs
      1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No
      increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004
      was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) =
      0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with
      HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However,
      MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P =
      0.04). No significant association between IkappaBL and MICA with RA was found.
      CONCLUSIONS: MICB*004 allele was associated with RA susceptibility. This allele
      was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association
      of MICB with RA susceptibility and the functional role of MIC genes in the
      pathogenesis of RA converts MICB into a candidate to be an additional MHC gene
      associated with RA susceptibility.

PMID- 17003178
TI  - Combat orthopaedics: a view from the trenches.
AB  - Approximately 70% of war wounds involve the musculoskeletal system, and military
      orthopaedic surgeons have assumed a pivotal role in the frontline treatment of
      these injuries in Iraq. Providing battlefield orthopaedic care poses special
      challenges; not only are many wounds unlike those encountered in civilian
      practice, but patients also must be triaged and treated in an austere and
      dangerous environment, undergo staged resuscitation and definitive surgery, and
      endure prolonged medical evacuation, often involving ground, helicopter, and
      fixed-wing transport across continents. Most orthopaedic wounds in Iraq are
      caused by exploding ordnance--frequently, improvised explosive devices, or IEDs.
      Because of advances in care, rapid medical evacuation, and modern body armor,
      many casualties have survived in Iraq who would not have done so in previous
      wars. Treatment of war wounds, many of which are devastating in the scope of soft
      tissue and bony injury, requires a team approach using hypotensive resuscitation,
      damage-control orthopaedics, new or rediscovered techniques of hemostatic and
      intravenous hemorrhage control, vacuum-assisted wound closure, and advanced
      reconstruction. Current challenges include prevention of infection, a better
      understanding of heterotopic ossification as a sequela of blast injury, and the
      need for a comprehensive, joint service database that encompasses the multilevel
      spectrum of orthopaedic care.

PMID- 17003179
TI  - Treatment of acute infection.
AB  - Military injuries are classically thought of as being limited to penetrating
      trauma caused by gunshot and blast injuries. However, blunt trauma caused by
      motor vehicle crashes and crush injuries can produce severe open injuries in the
      extremities. Most military injuries involve a higher level of energy than is
      commonly seen in civilian injuries, and the environment can be austere. These
      factors contribute to the development of infections that appear shortly after
      musculoskeletal trauma. Thus, the orthopaedic surgeon must know how to treat
      anaerobic soft-tissue infection, including clostridial fasciitis, clostridial
      myonecrosis, and tetanus; bacterial necrotizing fasciitis; and both superficial
      and deep bacterial wound infections.

PMID- 17003181
TI  - Moderators' summary: stabilization of long bones.

PMID- 17003180
TI  - Treatment of chronic infection.
AB  - Failure of an acute inflammatory response to resolve a wound infection heralds a
      cascade of events that affects the host and pathogens, culminating in a chronic,
      refractory condition. The factors contributing to this outcome include immune
      compromise of the host, antimicrobial resistance, wound-healing deficiencies, and
      the adherence of pathogens to themselves and wound surfaces via an impenetrable,
      resistant biofilm. To eradicate chronic infection, the pathogens, biofilm,
      surfaces available for adherence, and compromised tissue must be removed.

PMID- 17003182
TI  - Far-forward fracture stabilization: external fixation versus splinting.
AB  - With improvements in body armor, soldiers often survive previously fatal injuries
      but incur devastating extremity trauma. Orthopaedic and general surgeons in
      forward-deployed areas must be well-versed in the selection and application of
      both external fixation and splinting devices in order to best preserve life and
      limb of the wounded. The surgeon must consider tactical environment, injury
      severity, injury location, available resources, and his or her own level of
      experience. Advantages to using external fixation in the field include preventing
      future injury to the traumatized soft-tissue envelope, reducing the risk of
      infection, minimizing fracture hemorrhage, providing pain control, and
      facilitating medical evacuation. Splinting is reserved for closed, low-energy,
      stable fractures of either the upper or lower extremity and for unstable
      fractures that are not amenable to battlefield external fixation; because of the
      risks of compartment syndrome, casts are avoided.

PMID- 17003183
TI  - Conversion from temporary external fixation to definitive fixation: shaft
      fractures.
AB  - Temporary external fixation is the most common method of initial stabilization of
      diaphyseal fractures in forward surgical hospitals. Once the patient arrives at a
      stable environment, usually the United States, the fracture is managed with
      intramedullary nailing, small-pin external fixation, or a modified external
      fixator. Future research should be directed toward improving methods of care. It
      is not precisely known when is the best time to convert to definitive fixation
      without increasing the risk of infection. The risk factors leading to infection
      and nonunion are not well-established, making that determination even more
      difficult. Clinical studies of a suitable size should provide insight into these
      problems. Although temporary external fixation is commonly used, an optimal
      construct has not been determined. Data from studies of in vivo fracture-site
      motion after application of the temporary external fixator should be compared
      with biomechanical testing of similar constructs. These data could be used to
      recommend optimal temporary external fixation constructs of tibia, femur, and
      humerus fractures using currently available devices as well as to provide
      groundwork for the next generation of fixators.

PMID- 17003184
TI  - Conversion from external fixation to definitive fixation: periarticular injuries.
AB  - Extremity injuries sustained by uniformed service combatants pose a significant
      challenge to military orthopaedic surgeons. The wounding mechanisms in Operation
      Iraqi Freedom and Operation Enduring Freedom consist of blasts, penetrating
      injuries, and blunt injuries. The mortality of warriors has decreased overall
      because of the improvements in head, neck, and torso body armor. Consequently,
      the severity of extremity wounds has increased. Because of the far-forward
      surgical assets (surgeons and advanced equipment), these patients are stabilized
      rapidly and their injured extremities are treated early (ie, revascularized,
      debrided, stabilized). However, multiple challenges exist in the timing of
      definitive reconstructive efforts once these injured service members return to
      military medical centers in the continental United States.

PMID- 17003185
TI  - External fixation versus conversion to intramedullary nailing for definitive
      management of closed fractures of the femoral and tibial shaft.
AB  - External fixation for definitive therapy of closed diaphyseal femur and tibia
      fractures is the preferred method of treatment only in the pediatric population.
      In adult injuries, in particular open battle wounds, the timing of conversion of
      an external fixator to an intramedullary nail is determined by the condition of
      the soft tissues and the overall stability of the patient. In the tibia,
      conversion to an intramedullary nail is accomplished as expeditiously as
      possible. Early (< 2 weeks) conversion to an intramedullary implant may be
      accomplished safely. Increased infection rates have been documented when
      conversion is done after 2 weeks of external fixation. In the femur, conversion
      from external fixation to nailing is done as the patient's overall physical
      condition and soft tissues allow. Acute conversion to an intramedullary device in
      a single procedure is preferred in patients without evidence of pin-tract
      infection. Staged conversion to an intramedullary nail often requires a prolonged
      period of bed rest with skeletal traction to maintain fracture stability and
      patient comfort, with the attendant risks of pneumonia, decubiti, and
      thromboembolic events. Treatment of closed femoral and tibial diaphyseal
      fractures with external fixation, either definitively or as a bridge to
      intramedullary nailing, is a viable option in the patient with gross physiologic
      instability or an ipsilateral dysvascular limb. The decision to use definitive
      external fixation versus conversion to an intramedullary device should be made on
      a case-by-case basis. Additional prospective clinical studies are warranted to
      further delineate risks and benefits of these treatment modalities.

PMID- 17003186
TI  - Blast and penetrating fragment injuries to the extremities.
AB  - Blast injury to the extremities is the most common form of injury in recent
      military campaigns and in civilian terror attacks. Most orthopaedic trauma is
      caused by the secondary effect of blast--penetrating fragment injury. Timely
      wound debridement and excision of contaminated or avascular tissue, along with
      prevention of sepsis, are crucial to managing extremity injury. Late
      reconstruction and functional results are very challenging for the surgical team
      to achieve.

PMID- 17003187
TI  - Moderators' summary: management of segmental bone defects.

PMID- 17003188
TI  - Accelerated fracture healing.
AB  - Acceleration of the fracture healing process would have far-reaching benefits for
      both civilians and military personnel. Decreasing the time to return to complete
      function would reduce medical costs, enhance quality of life by decreasing pain
      and increasing mobility, accelerate the return of professional athletes to their
      sport, and decrease the time for military recruits to enter active duty after
      injuries incurred in basic training. Moreover, augmenting the healing process may
      prevent the long-term disability caused by fracture nonunion. Currently available
      pharmaceutical agents may allow us to realize this goal. However, these agents
      need to be tested in prospective randomized clinical trials.

PMID- 17003189
TI  - Tissue engineering solutions for traumatic bone loss.
AB  - Tissue engineering strategies for the repair, replacement, or augmentation of
      bone defects involves the use of cells, matrices, and bioregulatory factors. The
      source (endogenous, exogenous) and character of these factors, however, may vary
      greatly among the many approaches taken by current investigators. Although the
      results of current tissue engineering methods for regenerating bone have shown
      great promise, the extent of damage to extremities associated with war injuries
      may require the development of techniques that differ substantially from current
      practice.

PMID- 17003190
TI  - Response of musculoskeletal cells to biomaterials.
AB  - Many of our current therapies are based on information obtained in cell cultures
      using substrates that have little in common with the substrates the cells will
      encounter in vivo. To produce materials that are clinically valuable, we must
      analyze more deeply how musculoskeletal cells interact with the physical features
      of their environments. An increasing body of information has examined the
      mechanisms by which osteoblasts interact with their substrate. The underlying
      substrate, particularly in bone, also has structural features that can alter the
      mechanical environment experienced by the cells. These structural features
      modulate the nature of cell attachment and the resulting cell shape, affecting
      cell proliferation and differentiation. The chemistry, surface energy, and
      microarchitecture of a material all influence the kinds of proteins that adsorb
      onto the surface, which in turn affects integrin-mediated attachment. Signaling
      via integrins initiates the transfer of information to the cell about the
      microenvironment. Cells can differentiate between crystallinities of the same
      chemistry and distinguish complex differences in surface structure. These
      differences in the in vitro response correspond to differences in clinical
      effectiveness. By designing biomaterials that maximally enhance mesenchymal cell
      attachment, migration, proliferation, and differentiation, the value of these
      materials for tissue repair will be markedly increased. The goal is to provide
      materials that are capable of supporting tissue regeneration in vivo, often at
      sites compromised by infection and loss of structure.

PMID- 17003191
TI  - Management of segmental bony defects: the role of osteoconductive orthobiologics.
AB  - Our knowledge about, and the availability of, orthobiologic materials has
      increased exponentially in the last decade. Although previously confined to the
      experimental or animal-model realm, several orthobiologics have been shown to be
      useful in a variety of clinical situations. As surgical techniques in vascular
      anastomosis, soft-tissue coverage, limb salvage, and fracture stabilization have
      improved, the size and frequency of bony defects (commensurate with the severity
      of the initial injury) have increased, as well. Because all methods of managing
      segmental bony defects have drawbacks, a need remains for a readily available,
      void-filling, inexpensive bone substitute. Such a bone substitute fulfills a
      permissive role in allowing new bone to grow into a given defect. Such potential
      osteoconductive materials include ceramics, calcium sulfate or calcium phosphate
      compounds, hydroxyapatite, deproteinized bone, corals, and recently developed
      polymers. Some materials that have osteoinductive properties, such as
      demineralized bone matrix, also display prominent osteoconductive properties.

PMID- 17003192
TI  - Distraction osteogenesis.
AB  - The treatment of bone loss resulting from acute trauma has traditionally been a
      complex surgical problem. Numerous procedures have been devised to reconstitute
      bone stock, obtain fracture union, and provide a stable functional limb.
      Traditional internal bone transport has been used successfully for bony
      reconstruction for both acute and reconstructive bone loss. Potential
      complications are primarily related to the complexity of the external device,
      prolonged time in the frame, and nonunion of the docking and regenerate segments.
      Recent advances in fixator and pin design have reduced the complexity of these
      devices as well as the incidence of pin- and frame-related complications. Gradual
      shortening, rapid distraction using autodistractors, transporting over
      intramedullary devices, and using orthobiologic and adjuvant techniques to assist
      in the consolidation of regenerate and docking sites are now being combined to
      decrease the morbidity and excessive frame time required to complete these
      reconstructions.

PMID- 17003193
TI  - Vascularized fibula graft for the traumatically induced long-bone defect.
AB  - Long-bone defects resulting from trauma can be managed with a variety of
      techniques, including conventional bone grafting, distraction osteogenesis, bone
      graft substitutes, prosthetic devices, and vascularized bone grafting. Although
      there is an array of available methods for long-bone reconstruction of bony
      defects, vascularized bone transfer is particularly useful in large defects (> 6
      cm) and in cases in which osteomyelitis and unstable soft-tissue or beds make
      conventional techniques difficult.

PMID- 17003194
TI  - Moderators' summary: amputee care.

PMID- 17003195
TI  - The scope of wounds encountered in casualties from the global war on terrorism:
      from the battlefield to the tertiary treatment facility.
AB  - Injuries seen in Operation Iraqi Freedom range from those that can be managed
      with nonsurgical wound care only to those requiring amputation or multiple bony
      and soft-tissue procedures for limb salvage. The contamination and soft-tissue
      injury caused by exploding ordnance requires an aggressive treatment approach.
      Severe wounds treated near the battlefield (ie, level II) require meticulous
      surgical debridement, early fracture stabilization, broad-spectrum antibiotics,
      and rapid evacuation. Treatment at a level III combat support hospital involves a
      greater volume of patients and a longer stay because of the presence of Iraqi
      national patients. In the authors' experience, most US patients requiring
      surgical treatment were evacuated to a level IV facility (ie, Landstuhl Regional
      Medical Center) after one or two surgeries. The basic war surgery principles of
      aggressive resuscitation, early and thorough debridement, short-duration damage
      control surgical procedures, and rapid evacuation were critical in our reduction
      of wound infection rates to below 7% for all admissions.

PMID- 17003196
TI  - The United States Armed Forces Amputee Patient Care Program.
AB  - United States military amputees are treated at either Walter Reed Army Medical
      Center (Washington, DC) or Brooke Army Medical Center (Fort Sam Houston, TX). At
      each center, a multidisciplinary team from more than a dozen specialties works
      together to address the psychological, social, vocational, and spiritual needs of
      our soldiers, marines, sailors, and airmen, as well as their physical
      rehabilitation. Excellent outcomes are being achieved with the current practices
      of the Armed Forces Amputee Care Program, but a great deal of evidence-based
      research must be done to determine the optimal time to close the wound, the
      etiology of heterotopic ossification in blast injury, the factors determining
      optimal socket design, and the best sequence and timing for introduction of
      different prosthetic technologies in the rehabilitation process.

PMID- 17003197
TI  - Amputation is not isolated: an overview of the US Army Amputee Patient Care
      Program and associated amputee injuries.
AB  - Rates of amputation as a percentage of all combat injuries have increased
      significantly since the Korean War. Following traumatic and combat-related
      amputation, definitive treatment and rehabilitation require a large,
      multidisciplinary team to provide comprehensive medical and supportive care.
      Associated injuries are remarkably frequent, complicating treatment and
      potentially delaying rehabilitation and/or limiting outcomes. Patient and family
      psychosocial issues also must be assessed and appropriately addressed. The US
      Army Amputee Patient Care Program, with the support of numerous other government
      and private organizations, has been developed to meet the comprehensive medical,
      rehabilitative, and social needs of amputees injured in the current global war on
      terrorism, with the goal of maximizing subsequent patient outcomes utilizing a
      sports medicine approach.

PMID- 17003198
TI  - Heterotopic ossification in the residual limbs of traumatic and combat-related
      amputees.
AB  - Reports on the occurrence and treatment of heterotopic ossification in amputees
      are rare. Heterotopic ossification in the residual limbs of amputees may cause
      pain and skin breakdown and complicate or prevent optimal prosthetic fitting and
      utilization. Basic science research has shed light on the cellular and molecular
      basis for this disease process, but many questions remain unanswered. The recent
      experience of the military amputee centers with traumatic and combat-related
      amputations has demonstrated a surprisingly high prevalence of heterotopic
      ossification in residual limbs. Primary prophylactic regimens, such as
      nonsteroidal anti-inflammatory drugs and local irradiation, which have proved to
      be effective in preventing and limiting heterotopic ossification in other patient
      populations, have not been studied in amputees and generally are not feasible in
      the setting of acute traumatic amputation. When nonsurgical measures such as
      activity and repeated prosthetic modifications fail to provide relief, surgical
      excision has provided good early clinical results, with low rates of recurrence
      and acceptable complication rates in military amputees.

PMID- 17003199
TI  - Horizons in prosthesis development for the restoration of limb function.
AB  - The focus of our research program is the restoration of limb function through a
      biohybrid approach. We consider the limb conceptually as a biohybrid organ
      consisting of biological tissue, endoprostheses (including neural devices and
      joint replacements), and exoprostheses. The biohybrid limb maximizes biological
      function and functional articulations with optimized human-prosthesis interfaces.
      Our long-term goals are to create biomimetic prostheses, optimized control
      systems for prostheses, and optimized human-prosthesis interfaces using both limb
      lengthening and osseointegration techniques.

PMID- 17003201
TI  - Extremity war injuries: state of the art and future directions. Prioritized
      future research objectives.

PMID- 17003200
TI  - Factors influencing outcome following limb-threatening lower limb trauma: lessons
      learned from the Lower Extremity Assessment Project (LEAP).
AB  - The Lower Extremity Assessment Project (LEAP) is a multicenter study of severe
      lower extremity trauma in the US civilian population. At 2- and 7-year follow
      ups, the LEAP study found no difference in functional outcome between patients
      who underwent either limb salvage surgery or amputation. However, outcomes on
      average were poor for both groups. This study and others provide evidence of wide
      ranging variations in outcome following major limb trauma, with a substantial
      proportion of patients experiencing long-term disability. In addition, outcomes
      often are more affected by the patient's economic, social, and personal resources
      than by the initial treatment of the injury--specifically, amputation or
      reconstruction and level of amputation. A conceptual framework for examining
      outcomes after injury may be used to identify opportunities for interventions
      that would improve outcomes. Because of essential differences between the
      civilian and military populations, the findings of the LEAP study may correlate
      only roughly with combat casualty outcomes.

PMID- 17003202
TI  - Definitive treatment of combat casualties at military medical centers.
AB  - More than 9,000 casualties have been evacuated during the current conflict, and
      more than 40,000 orthopaedic surgical procedures have been performed. The most
      severely injured patients are treated in the United States at military medical
      centers. Individualized reconstructive plans are developed, and patients are
      treated with state-of-the-art techniques. Rehabilitation includes the assistance
      of the physical medicine and rehabilitation, physical therapy, and occupational
      therapy services, as well as, when necessary, psychiatric or other services. The
      extreme challenges of treating war-related soft-tissue defects include
      neurovascular injuries, burns, heterotopic ossification, infection, prolonged
      recovery, and persistent pain. Such injuries do not allow full restoration of
      function. Because of such devastating injuries, and despite use of up-to-date
      methods, outcomes can be less than optimal.

PMID- 17003203
TI  - Missile injuries of the limbs: an Iraqi perspective.
AB  - Missiles include pistol or rifle bullets, shell fragments, land mines, and
      grenades. Medium- and high-velocity missiles produce damage by laceration and
      crushing, shock waves, and cavitational effects. Low-velocity missiles produce
      damage by laceration and crushing only. Land mine injuries cause damage by the
      primary blast effect, secondarily by fragments, and thirdly by the effect induced
      by whole-body propulsion and by burns. Severity of injuries should be graded
      according to the degree of soft-tissue damage, bone defect or comminution, and
      vascular or neural injury. Among other factors, successful management of these
      injuries requires prompt and vigorous resuscitation, careful wound inspection,
      aggressive exploration, liberal debridement, and prompt removal of fragments. In
      addition, in these circumstances, one must stay alert for overlooked injuries and
      be aware of associated psychological trauma.

PMID- 17003204
TI  - Extremity trauma research in the United States Army.
AB  - Extremity wounds compose the burden of injury in the global war on terrorism, and
      there is a great need for research to improve the treatment of soldiers who incur
      these devastating injuries. The mission of the United States Army Institute of
      Surgical Research is to conduct combat casualty care research in several areas,
      including explosive injury mechanisms, field tourniquet use, external fixator pin
      coating, wound irrigation optimization, antibiotic-impregnated bone graft
      substitutes, segmental muscle defects, and outcomes research. Future research
      directions include development of bone and soft-tissue regenerative technologies,
      prevention and treatment of heterotopic ossification, and bacteriology of unique
      pathogens.

PMID- 17003206
TI  - From the battlefields to the states: the road to recovery. The role of Landstuhl
      Regional Medical Center in US military casualty care.
AB  - The transformation of the modern battlefield with respect to weaponry, modes of
      transportation, enemy capabilities and location, as well as technological
      advances, has greatly altered the tactical approach to the mission. Combat
      casualty care must continually evolve in response to the differences in types of
      injury, the number and triage of casualties, timing of treatment, and location of
      care. These battlefield changes have been demonstrated on a large scale in the
      global war on terrorism, which includes the military operations in Afghanistan
      and Iraq. The medical response has kept pace with this 21st-century conflict.
      Even in the new environment of armed conflict and with the advent of new
      technologies, the principles of managing orthopaedic combat casualties remain
      clear: preservation of life and limb, skeletal stabilization, and aggressive
      wound debridement. For United States service members wounded in the current
      conflicts, Landstuhl Regional Medical Center is a crucial stop along the road to
      recovery.

PMID- 17003205
TI  - Moderators' summary: wound management (session I).

PMID- 17003207
TI  - Timing of debridement of open fractures.
AB  - Although debridement within 6 to 8 hours of injury seems nearly universally
      accepted, the data supporting this recommendation are lacking. Most studies
      indicate that, in the context of modern antibiotic treatment, early debridement
      is not an independent predictor of decreased risk of infection. Achieving early
      debridement may pose unjustified risks to patient safety. Given the numerous
      factors that influence timing of surgical debridement in trauma centers, a
      prospective randomized trial of emergent versus urgent debridement is not
      feasible. However, a prospective longitudinal study could yield valuable data.

PMID- 17003208
TI  - Debridement of extremity war wounds.
AB  - The extent of surgery appropriate for limb wounds agreed on at the Inter-Allied
      Surgical Conference in 1917 included excision of the skin margin, generous
      extension of the wound, exploration through all layers, and excision of damaged
      muscle--techniques recognizable by all trauma surgeons today. The criteria for
      muscle viability (the four C's) include contraction on being pinched, consistency
      (not waxy or "stewed"), capillary bleeding when cut, and color (red, not pale or
      brown). Skin is excised with a narrow margin, fascia is generously released, all
      layers of the wound are explored and gross contamination removed, and nonviable
      muscle is excised. Some low-energy transfer wounds (eg, civilian handgun injury,
      military shrapnel wounds) involve little tissue damage and can safely be managed
      nonsurgically, provided that there is confidence in the assessment of wound
      severity. Questions remain regarding the safest and most effective way to assess
      wounds and select patients for surgical versus nonsurgical management.

PMID- 17003209
TI  - Timing of wound coverage in extremity war injuries.
AB  - Although several studies have been done on the timing of debridement of open
      fracture, none has specifically examined the effect of timing of soft-tissue
      coverage on outcome in the types of lower extremity injury being encountered in
      Iraq and Afghanistan, namely, injuries associated with the detonation of
      improvised explosive devices. Complex limb salvage requiring free tissue transfer
      or rotational flap coverage for soft-tissue defects has been commonly performed
      during the recent military conflicts in Iraq and Afghanistan. Current treatment
      protocols favor the inclusion of timely and stable axial limb fixation, radical
      debridement of all compromised soft tissues and osseous structures, and early
      wound closure with healthy, well-vascularized autologous tissue. In an attempt to
      minimize overall morbidity, a comprehensive plan must be made to sequentially
      reconstruct the involved extremity in order to achieve the highest level of
      function possible, with a durable construct, in the shortest period of time.
      Prospective studies are necessary to evaluate the effect of timing of coverage on
      outcome and on limb salvage.

PMID- 17003210
TI  - Standard wound coverage techniques for extremity war injury.
AB  - Reconstruction of extremity war injuries begins with aggressive forward
      resuscitative care and stabilization of the trauma patient. After serial care in
      progressively better supported medical environments, definitive management is
      done at the level V military treatment facility. Aggressive forward care coupled
      with rapid air transport has enabled increasingly complex care to be administered
      at the continental United States military facilities; however, it has also made
      the decision between limb salvage and amputation more challenging. Yet to be
      determined are (1) the optimal timing of definitive wound closure or coverage in
      coordination with fracture stabilization and (2) the optimal types of flap for
      both upper and lower extremity reconstruction. Records of patients with complex
      lower and upper extremity wounds who were treated at the National Naval Medical
      Center between September 2004 and June 2006 reveal useful short-term data. Longer
      term data, such as fracture union rate, time to ambulation, range of motion and
      global function of salvaged limbs, patient satisfaction with limb salvage, and
      average cost, are not yet available.

PMID- 17003211
TI  - Shrapnel management.
AB  - With the increased incidence of terrorism worldwide, it is important for surgeons
      to understand the role of shrapnel injury in mass casualty events. Several
      diagnostic modalities are available, including plain radiography, computed
      tomography, ultrasound, angiography, and computerized surgical navigation based
      on real-time acquisition of fluoroscopic data. Shrapnel management techniques are
      selected based on the following chronologic phases: acute, subacute, and late.

PMID- 17003212
TI  - Levels of medical care in the global war on terrorism.
AB  - Trauma care for military personnel injured in Iraq has become increasingly
      sophisticated. There are five levels, or echelons, of care, each progressively
      more advanced. Level I care provides immediate first aid at the front line. Level
      II care consists of surgical resuscitation provided by highly mobile forward
      surgical teams that directly support combatant units in the field. Level III care
      is provided through combat support hospitals--large facilities that take time to
      become fully operational but offer much more advanced medical, surgical, and
      trauma care, similar to a civilian trauma center. Level IV care is the first
      echelon at which definitive surgical management is provided outside the combat
      zone. Level V care is the final stage of evacuation to one of the major military
      centers in the United States, where definitive stabilization, reconstruction, or
      amputation of the injured extremity is performed.

PMID- 17003213
TI  - Moderators' summary: wound management (session II).

PMID- 17003214
TI  - Scope of wounds.
AB  - The scope of extremity wounds in the current conflict presents surgeons with new
      lessons to master. Unique to this conflict is a new type of patient, one with
      multiple and severely injured extremities who is otherwise free of serious
      injury. These injuries provide challenges to the medical system in terms of the
      volume and complexity of care, and to the patient and surgeon trying to achieve
      limb salvage and rehabilitation. These patients present with a combination of
      high-energy injury, massive evolving tissue destruction, and widespread
      contamination, resulting in an evolving zone of injury that respects no tissue
      planes, anatomic boundaries, or normal physiologic rules. We must ensure that our
      skills and techniques as surgeons evolve faster than do the injuries themselves.

PMID- 17003215
TI  - Treatment of blast injuries of the extremity.
AB  - Blast trauma is a complex event. Pathophysiologically, blast injuries are
      identified as primary (caused solely by the direct effect of blast overpressure
      on the tissue), secondary (caused by flying objects or fragments), tertiary
      (caused by bodily displacement), or quaternary (indirectly caused by the
      explosion). The range of primary blast injuries includes fractures, amputations,
      crush injury, burns, cuts, lacerations, acute occlusion of an artery, air
      embolism-induced injury, compartment syndrome, and others. Secondary injuries are
      the most common extremity blast injuries. Like primary injuries, they may
      necessitate limb amputation, be life-threatening, and produce severe
      contamination. Tertiary blast injuries of the extremity may result in traumatic
      amputations, fractures, and severe soft-tissue injuries. Quaternary injuries most
      often are burns. Following treatment and stabilization of immediate life
      threatening conditions, all patients are given antibiotic and tetanus
      prophylaxis. Debridement and wound excision are started as early as possible,
      with repeat debridement performed as necessary; fasciotomies also are performed
      to prevent compartment syndrome. Well-vascularized muscular free flaps provide
      soft-tissue coverage for blast-injured extremities. The closed-open technique of
      flap closure allows reexamination of the wound, further irrigation, debridement,
      and later bone and soft-tissue reconstruction.

PMID- 17003216
TI  - The contaminated high-energy open fracture: a protocol to prevent and treat
      inflammatory mediator storm-induced soft-tissue compartment syndrome (IMSICS).
AB  - The treatment modalities currently used in surgical debridement leave the
      traumatic wound with viable but tenuous tissue and a variable level of
      microcontaminants potentially laden with bacteria. In high-energy contaminated
      wounds, retention of these contaminants within the tenuous tissue of the so
      called zone of stasis can result in further tissue necrosis and the development
      of infection. A novel protocol for managing the high-energy contaminated open
      fracture involves two new techniques. First, Bernoulli's principle is used to
      facilitate a systematic excision of contaminants, as well as the wound surface to
      which they are adsorbed, by means of a high-velocity fluid stream. Second,
      topical negative pressure is established as a means to resuscitate the remaining
      edema-laden wound tissue to help avoid embarrassment to microcirculatory blood
      flow.

PMID- 17003217
TI  - Skin substitutes as alternatives to autografting in a wartime trauma setting.
AB  - Wartime injuries present extreme problems in wound management, with extensive
      skin degloving, deep tissue necrosis, and severe wound contamination. Several
      wound stabilization technologies, commonly used in burn and chronic wound
      treatment centers, have significantly advanced the treatment of wartime extremity
      trauma. Early skin coverage of these wounds is an ongoing challenge. Engineered
      skin substitutes offer advantages of expedited wound coverage and decreased donor
      site morbidity in the treatment of burns and chronic wounds. These substitutes,
      however, possess significant limitations when used in the presence of infection
      or full-thickness defects. Therefore, extrapolating the use of engineered skin
      substitutes to the coverage of acute war wounds is not clinically indicated. The
      timing and level of care in which skin substitutes could be applied for war
      wounds requires further clinical research.

PMID- 17003219
TI  - Moderators' summary: antibiotics and infection.

PMID- 17003218
TI  - New developments in flap techniques.
AB  - Limb reimplantation techniques using composite free-tissue transfer and
      microsurgical salvage of traumatized extremities have become standard
      reconstructive methods. Mechanisms for working with free-tissue transfers have
      advanced, specifically in regard to the use of thin-wire fixators: combining
      microsurgical techniques and thin-wire fixators helps in salvaging limbs that
      otherwise might be amputated. Also, combining the Ilizarov method with
      microsurgical techniques for limb salvage provides a new use for flaps. A further
      development in the use of flaps is the application of free-tissue transfers to
      preserve amputation levels in the war-injured. So-called fillet flaps serve as
      "spare parts" and can be customized for specific recipient sites. The so-called
      perforator flap makes use of feeder vessels, thus providing cutaneous and other
      composite flaps without sacrificing major vessels. Finally, the advent of the
      sural flap has made it possible to avoid microsurgical reconstruction but still
      provide adequate, well-vascularized cover, particularly in the distal third of
      the leg.

PMID- 17003220
TI  - Antibiotic prophylaxis: current recommendations.
AB  - Antibiotic prophylaxis consists of a brief course of antibiotics initiated
      preoperatively in order to decrease the risk of postoperative wound infection in
      the patient with a clean wound. The antibiotic should be started within 60
      minutes before skin incision and continued for not more than 24 hours. Antibiotic
      therapy is indicated for the contaminated or dirty wound. In open fractures,
      antibiotics should be started as soon as possible after injury and continued for
      3 days (type I and II fractures) or 5 days (type III). This treatment should be
      combined with local therapy consisting of antibiotic-impregnated
      polymethylmethacrylate beads. Although the utility of antibiotics in low-velocity
      gunshot wounds is controversial, high-velocity gunshot wounds should be treated
      with 48 to 72 hours of antibiotic therapy.

PMID- 17003221
TI  - Extremity war injuries: state of the art and future directions. Introduction.

PMID- 17003224
TI  - The 3'-untranslated region of the Ste20-like kinase SLK regulates SLK expression.
AB  - Ste20-like kinase, SLK, a germinal center kinase found in kidney epithelial
      cells, signals to promote apoptosis. Expression of SLK mRNA and protein and
      kinase activity are increased during kidney development and recovery from
      ischemic acute renal failure. The 3'-untranslated region (3'-UTR) of SLK mRNA
      contains multiple adenine and uridine-rich elements, suggesting that 3'-UTR may
      regulate mRNA stability. This was confirmed in COS cell transient transfection
      studies, which showed that expression of the SLK open-reading frame plus 3'-UTR
      mRNA was reduced by 35% relative to the open-reading frame alone. To further
      characterize the SLK-3'-UTR, this nucleotide sequence was subcloned downstream of
      enhanced green fluorescent protein (EGFP) cDNA. In COS, 293T, and glomerular
      epithelial cells, expression of EGFP mRNA and protein was markedly reduced in the
      presence of the SLK-3'-UTR. After transfection and subsequent addition of
      actinomycin D, EGFP mRNA remained stable in cells for at least 6 h, whereas EGFP
      SLK-3'-UTR mRNA decayed with a half-life of approximately 4 h. A region
      containing five AUUUA motifs within the SLK-3'-UTR destabilized EGFP mRNA.
      Deletion of this region from the SLK-3'-UTR, in part, restored mRNA stability. By
      UV cross-linking and SDS-PAGE, the SLK-3'-UTR bound to protein(s) of
      approximately 30 kDa in extracts of COS cells, glomerular epithelial cells, and
      kidney. Cotransfection of HuR (a RNA binding protein of approximately 30 kDa)
      increased the steady-state mRNA level of EGFP-SLK-3'-UTR but not EGFP. Thus the
      SLK-3'-UTR may interact with kidney RNA-binding proteins to regulate expression
      of SLK mRNA during kidney development and after ischemic injury.

PMID- 17003223
TI  - Resistance of mice lacking the serum- and glucocorticoid-inducible kinase SGK1
      against salt-sensitive hypertension induced by a high-fat diet.
AB  - Mineralocorticoids enhance expression and insulin stimulates activity of the
      serum- and glucocorticoid-inducible kinase SGK1, which activates the renal
      epithelial Na+)channel (ENaC). Under a salt-deficient diet, SGK1 knockout mice
      (sgk1-/-) excrete significantly more NaCl than their wild-type littermates
      (sgk1+/+) and become hypotensive. The present experiments explored whether SGK1
      participates in the hypertensive effects of a high-fat diet and high-salt intake.
      Renal SGK1 protein abundance of sgk1+/+ mice was significantly elevated after a
      high-fat diet. Under a control diet, fluid intake, blood pressure, urinary flow
      rate, and urinary Na+, K+, and Cl- excretion were similar in sgk1-/- and sgk1+/+
      mice. Under a standard diet, high salt (1% NaCl in the drinking water for 25
      days) increased fluid intake, urinary flow rate, and urinary Na+, K+, and Cl-
      excretion similarly in sgk1-/- and sgk1+/+ mice without significantly altering
      blood pressure. A high-fat diet alone (17 wk) did not significantly alter fluid
      intake, urinary flow rate, urinary Na+, K+, or Cl- excretion, or plasma
      aldosterone levels but increased plasma insulin, total cholesterol, triglyceride
      concentrations, and systolic blood pressure to the same extent in both genotypes.
      Additional salt intake (1% NaCl in the drinking water for 25 days) on top of a
      high-fat diet did not affect hyperinsulinemia or hyperlipidemia but increased
      fluid intake, urinary flow rate, and urinary NaCl excretion significantly more in
      sgk1-/- than in sgk1+/+ mice. Furthermore, in animals receiving a high-fat diet,
      additional salt intake increased blood pressure only in sgk1+/+ mice (to 132 +/-
      3 mmHg) but not in sgk1-/- mice (120 +/- 4 mmHg). Thus lack of SGK1 protects
      against the hypertensive effects of a combined high-fat/high-salt diet.

PMID- 17003222
TI  - Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic
      response to ANP in the pregnant rat.
AB  - Normal rat pregnancy is characterized by plasma volume expansion due to renal
      sodium retention and is associated with a blunted response to natriuretic
      stimuli, such as atrial natriuretic peptide (ANP). ANP signals via cGMP, and
      phosphodiesterases (PDE) inactivate cGMP and terminate the natriuretic response.
      We previously reported that increased medullary PDE-5 activity occurs in rat
      pregnancy, which may be the mechanism of the blunted natriuretic effect of ANP.
      Here, we used anesthetized 16-day pregnant and virgin rats to investigate whether
      intrarenal infusion of a selective PDE-5 inhibitor, sildenafil, would reverse the
      blunted response to ANP in pregnancy. We measured blood pressure, renal
      clearances using inulin and p-aminohippuric acid, and electrolyte excretion at
      baseline and during an ANP infusion. ANP caused a fall in mean arterial pressure
      in all groups, and sildenafil induced a further reduction. We observed an
      increase in sodium excretion with ANP in all rats, but this was blunted in the
      vehicle-infused pregnant rats. This could not be explained by differences in
      renal hemodynamics and was of tubular origin, as reflected by the reduced rise in
      fractional excretion of sodium with ANP in the pregnant rat given vehicle (45 +/-
      11 vs. 204 +/- 49%; P < 0.05). However, intrarenal sildenafil increased the
      natriuretic response and the rise in fractional excretion of sodium to the virgin
      value (226 +/- 23 vs. 245 +/- 73%; not significant), whereas the blunting
      persisted in the contralateral kidney. This demonstrates that increased
      intrarenal PDE-5 mediates the blunted natriuretic response to ANP during
      pregnancy and may contribute to the physiological volume expansion.

PMID- 17003225
TI  - Extracellular pH alkalinization by Cl-/HCO3- exchanger is crucial for TASK2
      activation by hypotonic shock in proximal cell lines from mouse kidney.
AB  - We have previously shown that K(+)-selective TASK2 channels and swelling
      activated Cl(-) currents are involved in a regulatory volume decrease (RVD;
      Barriere H, Belfodil R, Rubera I, Tauc M, Lesage F, Poujeol C, Guy N, Barhanin J,
      Poujeol P. J Gen Physiol 122: 177-190, 2003; Belfodil R, Barriere H, Rubera I,
      Tauc M, Poujeol C, Bidet M, Poujeol P. Am J Physiol Renal Physiol 284: F812-F828,
      2003). The aim of this study was to determine the mechanism responsible for the
      activation of TASK2 channels during RVD in proximal cell lines from mouse kidney.
      For this purpose, the patch-clamp whole-cell technique was used to test the
      effect of pH and the buffering capacity of external bath on Cl(-) and K(+)
      currents during hypotonic shock. In the presence of a high buffer concentration
      (30 mM HEPES), the cells did not undergo RVD and did not develop outward K(+)
      currents (TASK2). Interestingly, the hypotonic shock reduced the cytosolic pH
      (pH(i)) and increased the external pH (pH(e)) in wild-type but not in cftr (-/-)
      cells. The inhibitory effect of DIDS suggests that the acidification of pH(i) and
      the alkalinization of pH(e) induced by hypotonicity in wild-type cells could be
      due to an exit of HCO(3)(-). In conclusion, these results indicate that Cl(-)
      influx will be the driving force for HCO(3)(-) exit through the activation of the
      Cl(-)/HCO(3)(-) exchanger. This efflux of HCO(3)(-) then alkalinizes pH(e), which
      in turn activates TASK2 channels.

PMID- 17003226
TI  - Regulation of renal amino acid transporters during metabolic acidosis.
AB  - The kidney plays a major role in acid-base homeostasis by adapting the excretion
      of acid equivalents to dietary intake and metabolism. Urinary acid excretion is
      mediated by the secretion of protons and titratable acids, particularly ammonia.
      NH(3) is synthesized in proximal tubule cells from glutamine taken up via
      specific amino acid transporters. We tested whether kidney amino acid
      transporters are regulated in mice in which metabolic acidosis was induced with
      NH(4)Cl. Blood gas and urine analysis confirmed metabolic acidosis. Real-time RT
      PCR was performed to quantify the mRNAs of 16 amino acid transporters. The mRNA
      of phosphoenolpyruvate carboxykinase (PEPCK) was quantified as positive control
      for the regulation and that of GAPDH, as internal standard. In acidosis, the mRNA
      of kidney system N amino acid transporter SNAT3 (SLC38A3/SN1) showed a strong
      induction similar to that of PEPCK, whereas all other tested mRNAs encoding
      glutamine or glutamate transporters were unchanged or reduced in abundance. At
      the protein level, Western blotting and immunohistochemistry demonstrated an
      increased abundance of SNAT3 and reduced expression of the basolateral cationic
      amino acid/neutral amino acid exchanger subunit y(+)-LAT1 (SLC7A7). SNAT3 was
      localized to the basolateral membrane of the late proximal tubule S3 segment in
      control animals, whereas its expression was extended to the earlier S2 segment of
      the proximal tubule during acidosis. Our results suggest that the selective
      regulation of SNAT3 and y(+)LAT1 expression may serve a major role in the renal
      adaptation to acid secretion and thus for systemic acid-base balance.

PMID- 17003227
TI  - The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers
      amyloid-beta peptide levels in cell culture and mice.
AB  - Major characteristics of Alzheimer's disease (AD) are synaptic loss, cholinergic
      dysfunction, and abnormal protein depositions in the brain. The amyloid beta
      peptide (Abeta), a proteolytic fragment of amyloid beta precursor protein (APP),
      aggregates to form neuritic plaques and has a causative role in AD. A present
      focus of AD research is to develop safe Abeta-lowering drugs. A selective
      acetylcholinesterase inhibitor, phenserine, in current human trials lowers both
      APP and Abeta. Phenserine is dose-limited in animals by its cholinergic actions;
      its cholinergically inactive enantiomer, posiphen (+)-[phenserine], was assessed.
      In cultured human neuroblastoma cells, posiphen, like phenserine, dose- and time
      dependently lowered APP and Abeta levels by reducing the APP synthesis rate. This
      action translated to an in vivo system. Posiphen administration to mice (7.5-75
      mg/kg daily, 21 consecutive days) significantly decreased levels of total APP
      (tissue mass-adjusted) in a dose-dependent manner. Abeta40 and Abeta42 levels
      were significantly lowered by posiphen (> or =15 mg/kg) compared with controls.
      The activities of alpha-, beta-, and gamma-secretases were assessed in the same
      brain samples, and beta-secretase activity was significantly reduced. Posiphen,
      like phenserine, can lower Abeta via multiple mechanisms and represents an
      interesting drug candidate for AD treatment.

PMID- 17003228
TI  - The contribution of intestinal UDP-glucuronosyltransferases in modulating 7-ethyl
      10-hydroxy-camptothecin (SN-38)-induced gastrointestinal toxicity in rats.
AB  - Life-threatening diarrhea afflicts a considerable percentage of patients treated
      with irinotecan, an anticancer agent with effects elicited through its active
      metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). The primary detoxification
      pathway for SN-38 is glucuronidation. The purpose of this study was to evaluate
      the role that intestinal UDP-glucuronosyltransferases (UGTs) have from hepatic
      UGTs in modulating this diarrhea. To investigate this, Gunn rats devoid of UGT1A
      activity were injected with recombinant adenoviral vectors expressing UGT1A1,
      1A6, and 1A7, resulting in reconstituted hepatic UGT expression comparable to a
      heterozygote. Hepatic microsome studies indicated that 4 to 7 days after
      adenoviral injection, transfected Gunn rats (j/jAV) had SN-38 glucuronide (SN
      38G) formation rates three times higher than control heterozygote rats (j+AV).
      The adenovirus did not impart any glucuronidating capacity to the intestine in
      j/jAV rats, whereas j+AV rats possessed intestinal UGT function. After the
      administration of 20 mg/kg/day irinotecan i.p. to j/jAV rats 4 days after
      adenovirus injection, diarrhea ensued before the fourth irinotecan dose. j+AV
      rats were spared the diarrhea, and the toxicity was mild compared with the j/jAV
      rats, as measured by diarrhea scores, weight loss, and histological assessments
      of the cecum and colon. The pharmacokinetics of irinotecan, SN-38, and SN-38G
      indicate that the systemic exposure of SN-38 and SN-38G was higher and lower,
      respectively, in j/jAV rats. Despite this, the biliary excretion of irinotecan
      and metabolites was similar. Because intestinal UGTs are the main discriminating
      factor between j/jAV and j+AV rats, their presence seems to be critical for the
      gastrointestinal protection observed in j+AV rats.

PMID- 17003229
TI  - Cardioprotective effects of a novel iron chelator, pyridoxal 2-chlorobenzoyl
      hydrazone, in the rabbit model of daunorubicin-induced cardiotoxicity.
AB  - Iron chelation is the only pharmacological intervention against anthracycline
      cardiotoxicity whose effectiveness has been well documented both experimentally
      and clinically. In this study, we aimed to assess whether pyridoxal 2
      chlorobenzoyl hydrazone (o-108, a strong iron chelator) can provide effective
      protection against daunorubicin (DAU)-induced chronic cardiotoxicity in rabbits.
      First, using the HL-60 leukemic cell line, it was shown that o-108 has no
      potential to blunt the antiproliferative efficacy of DAU. Instead, o-108 itself
      moderately inhibited cell proliferation. In vivo, chronic DAU treatment (3 mg/kg
      weekly for 10 weeks) induced mortality (33%), left ventricular (LV) dysfunction,
      a troponin T rise, and typical morphological LV damage. In contrast, all animals
      treated with 10 mg/kg o-108 before DAU survived without a significant drop in the
      LV ejection fraction (63.2 +/- 0.5 versus 59.2 +/- 1.0%, beginning versus end,
      not significant), and their cardiac contractility (dP/dt(max)) was significantly
      higher than in the DAU-only group (1131 +/- 125 versus 783 +/- 53 kPa/s, p <
      0.05), which corresponded with histologically assessed lower extent and intensity
      of myocardial damage. Although higher o-108 dose (25 mg/kg) was well tolerated
      when administered alone, in combination with DAU it led to rather paradoxical and
      mostly negative results regarding both cardioprotection and overall mortality. In
      conclusion, we show that shielding of free intracellular iron using a potent
      lipophilic iron chelator is able to offer a meaningful protection against chronic
      anthracycline cardiotoxicity. However, this approach lost its potential with the
      higher chelator dose, which suggests that iron might play more complex role in
      the pathogenesis of this disease than previously assumed.

PMID- 17003230
TI  - Transport, metabolism, and in vivo population pharmacokinetics of the chloro
      benztropine analogs, a class of compounds extensively evaluated in animal models
      of drug abuse.
AB  - Recently, extensive behavioral research has been conducted on the benztropine
      (BZT) analogs with the goal of developing successful therapeutics for cocaine
      abuse. The present study was conducted to characterize the contribution of
      dispositional factors in mediating the behavioral differences among the chloro
      BZT analogs and to identify cytochrome P450 enzymes involved in their metabolism.
      Bidirectional transport and efflux studies of four of the chloro BZT analogs were
      conducted. Screening with a panel of human and rat Supersomes was performed for
      4',4''-diCl BZT. In addition, pharmacokinetic and brain distribution studies for
      4'-Cl and 4',4''-diCl BZT in Sprague-Dawley rats were conducted. The permeability
      of the chloro analogs ranged from 8.26 to 32.23 and from 1.37 to 21.65 x 10(-6)
      cm/s, whereas the efflux ratios ranged from 2.1 to 6.9 and from 3.3 to 28.4
      across Madin-Darby canine kidney-multidrug resistance 1 (MDCK-MDR1) and Caco-2
      monolayers, respectively. The P-glycoprotein (P-gp) inhibitor verapamil reduced
      the efflux ratios and enhanced the absorptive transport of the chloro BZT
      analogs. 4',4''-diCl BZT was a substrate of human CYP2D6 and 2C19 and rat 2C11
      and 3A1. The brain uptake for 4'-Cl and 4',4''-diCl BZT was comparable and higher
      than previously reported for cocaine (brain-to-plasma partition coefficient = 4.6
      4.7 versus 2.1 for cocaine). The rank order for t(1/2) was 4',4''-diCl BZT >> 4'
      Cl BZT > cocaine and for steady-state volume of distribution was 4'-Cl BZT >
      4',4''-diCl BZT >> cocaine. In conclusion, the chloro analogs differ
      significantly in their clearance and duration of action, which correlates to
      their behavioral profiles and abuse liability. Furthermore, these results suggest
      that the distinctive behavioral profile of these analogs is not due to limited
      brain exposure.

PMID- 17003231
TI  - Cyclooxygenase, p38 mitogen-activated protein kinase (MAPK), extracellular signal
      regulated kinase MAPK, Rho kinase, and Src mediate hydrogen peroxide-induced
      contraction of rat thoracic aorta and vena cava.
AB  - In hypertension, blood vessels exhibit increased reactive oxygen species
      production that may alter vascular tone. We previously observed that H2O2
      contracted rat thoracic vena cava under resting tone and aorta contracted with
      KCl. In arteries but not veins, H2O2-induced contraction required extracellular
      Ca2+ influx. Because of this difference in Ca2+ utilization, we hypothesized that
      signaling pathways mediating H2O2-induced contraction in vena cava under resting
      tone differed from those mediating H2O2-induced contraction in aorta contracted
      with KCl. Inhibitors of cyclooxygenase (COX) 1 and 2 (indomethacin, 10 microM),
      thromboxane A2 (TXA2) receptors [ICI185282 (2RS,4RS,5SR-4-o-hydroxyphenyl-2
      trifluoromethyl-1,3-dioxan-5-yl heptenoic acid), 10 microM], p38 mitogen
      activated protein kinase (MAPK) [SB203580 (4-[5-(4-fluorophenyl)-2-[4
      (methylsulfonyl)phenyl]-1H-imidazol-4-yl]pyridine), 10 microM], extracellular
      signal-regulated kinase (Erk) [PD98059 (2'-amino-3'-methoxyflavone), 10 microM],
      src [PP1 (4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, 10
      microM], and rho kinase [Y27632 (trans-4-[(1R)-1-aminoethyl]-N-4
      pyridinylcyclohexanecarboxamide dihydrochloride), 10 microM], significantly
      reduced H2O2-induced contraction in vena cava under resting tone and aorta after
      KCl (30 mM) contraction. In contrast, the phosphatidylinositol 3-kinase (PI3-K)
      inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, 20 microM]
      did not reduce aortic or venous H2O2-induced contraction. p38 MAPK, Erk MAPK, and
      src inhibition did not reduce aortic or venous contraction to the TXA2 receptor
      agonist U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy PGF(2alpha), 1 microM),
      whereas rho kinase inhibition significantly reduced aortic and venous contraction
      to U46619, and PI3-K inhibition reduced venous contraction to U46619. Our data
      suggest that, in rat thoracic aorta and vena cava, a COX-derived metabolite is
      one important mediator of H2O2 contraction, possibly via rho kinase activation,
      and that H2O2-induced contraction via p38 and Erk MAPK probably occurs
      independently of TXA2 receptor activation.

PMID- 17003232
TI  - Phosphorylation of endothelial nitric-oxide synthase is diminished in mesenteric
      arteries from septic rabbits depending on the altered phosphatidylinositol 3
      kinase/Akt pathway: reversal effect of fluvastatin therapy.
AB  - Endothelial dysfunction plays a crucial role in the pathophysiology of sepsis.
      Alterations in endothelial nitric-oxide synthase (eNOS) may contribute to the
      impaired endothelial function. We investigated whether the regulatory mechanism
      for eNOS phosphorylation and activation is altered in a rabbit lipopolysaccharide
      induced septic model. Following induction of sepsis, a time-dependent marked
      reduction in eNOS phosphorylation was observed in mesenteric arteries, with a
      significant decrease in eNOS expression. Likewise, Akt phosphorylation was
      progressively and profoundly reduced, although total Akt remained unchanged.
      Furthermore, the amounts of the two subunits of phosphatidylinositol 3-kinase
      (PI3-K) in the membranous pool were diminished without changes in the total
      amount of the PI3-K heterodimer, indicating a decrease in translocation to the
      membranes. In vivo treatment with fluvastatin restored the decrease in eNOS
      phosphorylation in septic mesenteric vessels. This was possibly the result of the
      recovery of Akt phosphorylation. Treatment with the PI3-K inhibitor wortmannin
      partially inhibited the fluvastatin-induced increases in phosphorylation of Akt
      and eNOS, and the decrease in translocation of PI3-K heterodimer to the membranes
      during sepsis was slightly improved by fluvastatin. Sepsis-induced impairment of
      eNOS expression was also nearly normalized by fluvastatin. It is noteworthy that
      rabbits treated with fluvastatin exhibited a dramatic improvement in sepsis
      survival. The present results showed vascular abnormalities of the PI3-K/Akt
      pathway involved in the impairment of eNOS phosphorylation and activation in
      sepsis. We also suggest that fluvastatin would ameliorate vascular endothelial
      dysfunction, in part, presumably via its recovery effect on Akt-dependent eNOS
      phosphorylation. It may be potentially useful for therapy of sepsis.

PMID- 17003234
TI  - Intrauterine growth restriction is associated with alterations in placental
      lipoprotein receptors and maternal lipoprotein composition.
AB  - Among other factors, fetal growth requires maternal supply of cholesterol.
      Cellular cholesterol uptake is mainly mediated by the LDL receptor (LDL-R) and
      the scavenger receptor family. We hypothesized that expression levels of key
      receptors of these families were regulated differently in placentas from IUGR
      pregnancies with varying degrees of severity. Third-trimester placentas from IUGR
      pregnancies with (IUGR-S) and without (IUGR-M) fetal hemodynamic changes and from
      control (AGA) pregnancies were studied. LDL-R, LDL-R-related protein (LRP-1), and
      scavenger receptor class B type I (SR-BI) mRNA and protein levels were measured.
      Cholesterol concentration and composition of lipoproteins were analyzed
      enzymatically and by lipid electrophoresis, respectively, in maternal and
      umbilical cord blood. LDL-R mRNA levels in IUGR-M were similar to AGA but lower
      (P < 0.05) in IUGR-S. In contrast, LDL-R protein was twofold (IUGR-M) and 1.8
      fold (IUGR-S) higher (P < 0.05) than in the AGA group. LRP-1 mRNA and protein
      levels were not altered in the IUGR cases. SR-BI mRNA was unchanged in IUGR, but
      protein levels were lower (P < 0.05) in IUGR-S than in the other groups. Maternal
      plasma concentrations of LDL cholesterol were higher (P < 0.05) in the AGA group
      (188.5 +/- 23.6 mg/dl) than in the IUGR-S group (154.2 +/- 26.1). Electrophoretic
      mobility of the LDL fraction in maternal plasma demonstrated significant changes
      in migration toward higher values (AGA 0.95 +/- 0.06, IUGR-M 1.12 +/- 0.11, P <
      0.001; IUGR-S 1.28 +/- 0.20, P = 0.002). We conclude that LDL-R and SR-BI levels
      are altered in IUGR pregnancies. These differences were associated with changes
      in LDL, but not HDL, mobility and cholesterol concentration in maternal
      circulation.

PMID- 17003233
TI  - Effects of glucose-dependent insulinotropic peptide on osteoclast function.
AB  - Acute nutrient ingestion leads to a rapid inhibition of bone resorption while
      effects on makers of bone formation are less marked or absent, suggesting that
      there is a transient shift toward skeletal accretion in the immediate
      postprandial period. The cellular bases for these effects are not clear. Glucose
      dependent insulinotropic peptide (GIP), a known modulator of glucose-induced
      insulin secretion, is secreted from intestinal endocrine cells in response to
      nutrient ingestion. In addition to the effect of GIP on pancreatic beta-cells,
      GIP receptors are expressed by osteoclastic cells [corrected] in bone, suggesting
      a role for this incretin hormone in bone formation. To determine whether GIP also
      plays a role in the anti-resorptive effect of nutrient ingestion, osteoclasts
      were analyzed for the presence of GIP receptors by PCR, immunohistochemical and
      immunocytochemical analyses of bone tissue, and freshly isolated mature
      osteoclasts and osteoclast-like cells cultured in vitro. Osteoclast function was
      assessed by fetal long bone resorption assay and by use of the Osteologic disc
      assay. Our results demonstrate that GIP receptor transcripts and protein are
      present in osteoclasts. In addition, with the use of an in vitro organ culture
      system and mature osteoclasts, GIP was found to inhibit bone resorption in the
      organ culture system and the resorptive activity of mature osteoclasts. These
      data are consistent with the hypothesis that GIP inhibits bone breakdown through
      a direct effect on osteoclast-resorptive activity and suggest one mechanism for
      the postprandial reduction in markers of bone breakdown.

PMID- 17003235
TI  - Activation of glycogen synthase in myocardium induced by intermittent hypoxia is
      much lower in fasted than in fed rats.
AB  - Obstructive sleep apnea is characterized by intermittent obstruction of the upper
      airway, which leads to intermittent hypoxia. Myocardial glycogen is a major
      energy resource for heart during hypoxia. Previous studies have demonstrated that
      intermittent hypoxia rapidly degrades myocardial glycogen and activates glycogen
      synthase (GS). However, the underlying mechanisms remain undefined. Because sleep
      apnea/intermittent hypoxia usually happens at night, whether intermittent hypoxia
      leads to GS activation in the postabsorptive state is not known. In the present
      study, male adult rats were studied after either an overnight fast or ad libitum
      feeding with or without intermittent ventilatory arrest (3 90-s periods at 10-min
      intervals). Hearts were quickly excised and freeze-clamped. Intermittent hypoxia
      induced a significant decrease in myocardial glycogen content in fed rats and
      stimulated GS in both fasted and fed rats. However, the portion of GS in the
      active form increased by approximately 38% in fasted rats compared with a larger,
      approximately 130% increase in fed rats. The basal G-6-P content was comparable
      in fasted and fed animals and increased approximately threefold after hypoxia.
      The basal phosphorylation states of Akt and GSK-3beta and the activity of protein
      phosphatase 1 (PP1) were comparable between fasted and fed control rats. Hypoxia
      significantly increased Akt phosphorylation and PP1 activity only in fed rats. In
      contrast, hypoxia did not induce significant change in GSK-3beta phosphorylation
      in either fasted or fed rats. We conclude that hypoxia activates GS in fed rat
      myocardium through a combination of rapid glycogenolysis, elevated local G-6-P
      content, and increased PP1 activity, and fasting attenuates this action
      independent of local G-6-P content.

PMID- 17003236
TI  - A proposed nomenclature consensus for the myostatin gene family.

PMID- 17003237
TI  - Calcium receptor stimulates chemotaxis and secretion of MCP-1 in GnRH neurons in
      vitro: potential impact on reduced GnRH neuron population in CaR-null mice.
AB  - The factors controlling the migration of mammalian gonadotropin-releasing hormone
      (GnRH) neurons from the nasal placode to the hypothalamus are not well
      understood. We studied whether the extracellular calcium-sensing receptor (CaR)
      promotes migration/chemotaxis of GnRH neurons. We demonstrated expression of CaR
      in GnRH neurons in the murine basal forebrain and in two GnRH neuronal cell
      lines: GT1-7 (hypothalamus derived) and GN11 (olfactory bulb derived). Elevated
      extracellular Ca(2+) concentrations promoted chemotaxis of both cell types, with
      a greater effect in GN11 cells. This effect was CaR mediated, as, in both cell
      types, overexpression of a dominant-negative CaR attenuated high Ca(2+)
      stimulated chemotaxis. We also demonstrated expression of a beta-chemokine,
      monocyte chemoattractant protein-1 (MCP-1), and its receptor, CC motif receptor-2
      (CCR2), in the hypothalamic GnRH neurons as well as in GT1-7 and GN11 cells.
      Exogenous MCP-1 stimulated chemotaxis of both cell lines in a dose-dependent
      fashion; the effect was greater in GN11 than in GT1-7 cells, consistent with the
      higher CCR2 mRNA levels in GN11 cells. Activating the CaR stimulated MCP-1
      secretion in GT1-7 but not in GN11 cells. MCP-1 secreted in response to CaR
      stimulation is biologically active, as conditioned medium from GT1-7 cells
      treated with high Ca(2+) promoted chemotaxis of GN11 cells, and this effect was
      partially attenuated by a neutralizing antibody to MCP-1. Finally, in the
      preoptic area of anterior hypothalamus, the number of GnRH neurons was
      approximately 27% lower in CaR-null mice than in mice expressing the CaR gene. We
      conclude that the CaR may be a novel regulator of GnRH neuronal migration likely
      involving, in part, MCP-1.

PMID- 17003238
TI  - Hormone, cytokine, and nutritional regulation of sepsis-induced increases in
      atrogin-1 and MuRF1 in skeletal muscle.
AB  - Various atrophic stimuli increase two muscle-specific E3 ligases, muscle RING
      finger 1 (MuRF1) and atrogin-1, and knockout mice for these "atrogenes" display
      resistance to denervation-induced atrophy. The present study determined whether
      increased atrogin-1 and MuRF1 mRNA are mediated by overproduction of endogenous
      glucocorticoids or inflammatory cytokines in adult rats and whether atrogene
      expression can be downregulated by anabolic agents such as insulin-like growth
      factor (IGF)-I and the nutrient-signaling amino acid leucine. Both atrogin-1 and
      MuRF1 mRNA in gastrocnemius was upregulated dose and time dependently by
      endotoxin. Additionally, peritonitis produced by cecal ligation and puncture
      increased atrogin-1 and MuRF1 mRNA in gastrocnemius (but not soleus or heart) by
      8 h, which was sustained for 72 and 24 h, respectively. Whereas the sepsis
      induced increase in atrogin-1 expression was completely prevented by IGF-I, the
      increased MuRF1 was not altered. In contrast to the IGF-I effect, the sepsis
      induced increased mRNA of both atrogenes was unresponsive to either acute or
      repetitive administration of leucine. Whereas exogenous infusion of TNF-alpha
      increased atrogin-1 and MuRF1 in gastrocnemius, pretreatment of septic rats with
      the TNF antagonist TNF-binding protein did not prevent increased expression of
      either atrogene. Similarly, whereas dexamethasone increased atrogene expression,
      pretreatment with the glucocorticoid receptor antagonist RU-486 failed to
      ameliorate the sepsis-induced increase in atrogin-1 and MuRF1. Thus, under in
      vivo conditions in mature adult rats, the sepsis-induced increase in muscle
      atrogin-1 and MuRF1 mRNA appears both glucocorticoid and TNF independent and is
      unresponsive to leucine.

PMID- 17003239
TI  - High-calcium diet modulates effects of long-term prolactin exposure on the
      cortical bone calcium content in ovariectomized rats.
AB  - High physiological prolactin induced positive calcium balance by stimulating
      intestinal calcium absorption, reducing renal calcium excretion, and increasing
      bone calcium deposition in female rats. Although prolactin-induced increase in
      trabecular bone calcium deposition was absent after ovariectomy, its effects on
      cortical bones were still controversial. The present investigation, therefore,
      aimed to study the effect of in vivo long-term high physiological prolactin
      induced by either anterior pituitary (AP) transplantation or 2.5 mg/kg prolactin
      injection on cortical bones in ovariectomized rats. Since the presence of
      prolactin receptors (PRLR) in different bones of normal adult rats has not been
      reported, we first determined mRNA expression of both short- and long-form PRLRs
      at the cortical sites (tibia and femur) and trabecular sites (calvaria and
      vertebrae) by using the RT-PCR. Our results showed the mRNA expression of both
      PRLR isoforms with predominant long form at all sites. However, high prolactin
      levels induced by AP transplantation in normal rats did not have any effect on
      the femoral bone mineral density or bone mineral content. By using (45)Ca kinetic
      study, 2.5 mg/kg prolactin did not alter bone formation, bone resorption, calcium
      deposition, and total calcium content in tibia and femur of adult ovariectomized
      rats. AP transplantation also had no effect on the cortical total calcium content
      in adult ovariectomized rats. Because previous work showed that the effects of
      prolactin were age dependent and could be modulated by high-calcium diet,
      interactions between prolactin and these two parameters were investigated. The
      results demonstrated that 2.0% wt/wt high-calcium diet significantly increased
      the tibial total calcium content in 9-wk-old young AP-grafted ovariectomized rats
      but decreased the tibial total calcium content in 22-wk-old adult rats. As for
      the vertebrae, the total calcium contents in both young and adult rats were not
      changed by high-calcium diet. The present results thus indicated that the adult
      cortical bones were potentially direct targets of prolactin. Moreover, the
      effects of high physiological prolactin on cortical bones were age dependent and
      were observed only under the modulation of high-calcium diet condition.

PMID- 17003240
TI  - Expression and localization of androgen receptor-interacting protein-4 in the
      testis.
AB  - Androgen receptor-interacting protein 4 (ARIP4) belongs to the SNF2 family of
      proteins involved in chromatin remodeling, DNA excision repair, and homologous
      recombination. It is a DNA-dependent ATPase, binds to DNA and mononucleosomes,
      and interacts with androgen receptor (AR) and modulates AR-dependent
      transactivation. We have examined in this study the expression and cellular
      localization of ARIP4 during postnatal development of mouse testis. ARIP4 was
      detected by immunohistochemistry in Sertoli cell nuclei at all ages studied,
      starting on day 5, and exhibited the highest expression level in adult mice. At
      the onset of spermatogenesis, ARIP4 expression became evident in spermatogonia,
      pachytene, and diplotene spermatocytes. Immunoreactive ARIP4 antigen was present
      in Leydig cell nuclei. In Sertoli cells ARIP4 was expressed in a stage-dependent
      manner, with high expression levels at stages II-VI and VII-VIII. ARIP4
      expression patterns did not differ significantly in testes of wild-type, follicle
      stimulating hormone receptor knockout, and luteinizing hormone receptor knockout
      mice. In testes of hypogonadal mice, ARIP4 was found mainly in interstitial cells
      and exhibited lower expression in Sertoli and germ cells. In vitro stimulation of
      rat seminiferous tubule segments with testosterone, FSH, or forskolin did not
      significantly change stage-specific levels of ARIP4 mRNA. Heterozygous ARIP4(+/-)
      mice were haploinsufficient and had reduced levels of Sertoli-cell specific
      androgen-regulated Rhox5 (also called Pem) mRNA. Collectively, ARIP4 is an AR
      coregulator in Sertoli cells in vivo, but the expression in the germ cells
      implies that it has also AR-independent functions in spermatogenesis.

PMID- 17003241
TI  - Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of
      fetal and maternal sheep.
AB  - Maternal ethanol intake during pregnancy impairs fetal growth, but mechanisms are
      not clearly defined. Reduced IGF abundance or bioavailability in the fetus and/or
      mother may contribute to this growth restriction. We hypothesized that an episode
      of acute ethanol exposure, mimicking binge drinking would restrict fetal growth
      and perturb the maternal and fetal IGF axes. Pregnant sheep were infused
      intravenously with saline or ethanol (1 g/kg maternal wt) over 1 h, on days 116,
      117, and 118 of gestation (start of 1st infusion = time 0, term is 147 days).
      Maternal and fetal plasma IGF and IGF-binding protein (IGFBP) concentrations were
      measured before and after each infusion. Compared with controls, ethanol exposure
      reduced fetal weight at day 120 by 19%, transiently reduced maternal plasma IGF-I
      (-35%) at 30 h, and decreased fetal plasma IGF-II (-28%) from 24 to 54 h after
      the first infusion. Ethanol exposure did not alter maternal or fetal plasma
      concentrations of IGFBP-2 and IGFBP-3, measured by Western ligand blotting. We
      conclude that suppression of maternal and fetal IGF abundance may contribute to
      fetal growth restriction induced by acute or binge ethanol exposure.

PMID- 17003242
TI  - Lipid-induced beta-cell dysfunction in vivo in models of progressive beta-cell
      failure.
AB  - We determined the effect of 48-h elevation of plasma free fatty acids (FFA) on
      insulin secretion during hyperglycemic clamps in control female Wistar rats
      (group a) and in the following female rat models of progressive beta-cell
      dysfunction: lean Zucker diabetic fatty (ZDF) rats, both wild-type (group b) and
      heterozygous for the fa mutation in the leptin receptor gene (group c); obese
      (fa/fa) Zucker rats (nonprediabetic; group d); obese prediabetic (fa/fa) ZDF rats
      (group e); and obese (fa/fa) diabetic ZDF rats (group f). FFA induced insulin
      resistance in all groups but increased C-peptide levels (index of absolute
      insulin secretion) only in obese prediabetic ZDF rats. Insulin secretion
      corrected for insulin sensitivity using a hyperbolic or power relationship
      (disposition index or compensation index, respectively, both indexes of beta-cell
      function) was decreased by FFA. The decrease was greater in normoglycemic
      heterozygous lean ZDF rats than in Wistar controls. In obese "prediabetic" ZDF
      rats with mild hyperglycemia, the FFA-induced decrease in beta-cell function was
      no greater than that in obese Zucker rats. However, in overtly diabetic obese ZDF
      rats, FFA further impaired beta-cell function. In conclusion, 1) the FFA-induced
      impairment in beta-cell function is accentuated in the presence of a single copy
      of a mutated leptin receptor gene, independent of hyperglycemia. 2) In
      prediabetic ZDF rats with mild hyperglycemia, lipotoxicity is not accentuated, as
      the beta-cell mounts a partial compensatory response for FFA-induced insulin
      resistance. 3) This compensation is lost in diabetic rats with more marked
      hyperglycemia and loss of glucose sensing.

PMID- 17003243
TI  - Effects of streptozotocin-induced diabetes and physical training on gene
      expression of titin-based stretch-sensing complexes in mouse striated muscle.
AB  - In striated muscle, a sarcomeric noncontractile protein, titin, is proposed to
      form the backbone of the stress- and strain-sensing structures. We investigated
      the effects of diabetes, physical training, and their combination on the gene
      expression of proteins of putative titin stretch-sensing complexes in skeletal
      and cardiac muscle. Mice were divided into control (C), training (T),
      streptozotocin-induced diabetic (D), and diabetic training (DT) groups. Training
      groups performed for 1, 3, or 5 wk of endurance training on a motor-driven
      treadmill. Muscle samples from T and DT groups together with respective controls
      were collected 24 h after the last training session. Gene expression of calf
      muscles (soleus, gastrocnemius, and plantaris) and cardiac muscle were analyzed
      using microarray and quantitative PCR. Diabetes induced changes in mRNA
      expression of the proteins of titin stretch-sensing complexes in Z-disc (MLP,
      myostatin), I-band (CARP, Ankrd2), and M-line (titin kinase signaling). Training
      alleviated diabetes-induced changes in most affected mRNA levels in skeletal
      muscle but only one change in cardiac muscle. In conclusion, we showed diabetes
      induced changes in mRNA levels of several fiber-type-biased proteins (MLP,
      myostatin, Ankrd2) in skeletal muscle. These results are consistent with previous
      observations of diabetes-induced atrophy leading to slower fiber type
      composition. The ability of exercise to alleviate diabetes-induced changes may
      indicate slower transition of fiber type.

PMID- 17003246
TI  - The effect of graphic organizers on subjective and objective comprehension of a
      health education text.
AB  - This study examined the effect of graphic organizers on the comprehension of a
      health education brochure text and compared subjective with objective
      comprehension measures. Graphic organizers are graphical depictions of relations
      among concepts in a text. Participants read a brochure text about asthma with and
      without these organizers, and subjective and objective text comprehension was
      measured. It was found that graphic organizers had effects on four levels of
      objective comprehension as indicated by open comprehension questions. However, on
      the subjective comprehension measure using Likert-type scales, the groups with
      and without graphic organizers did not differ from each other. It is concluded
      that health education texts could benefit from relatively simple techniques to
      increase comprehension. Furthermore, in developing health education materials,
      comprehension should be measured objectively.

PMID- 17003244
TI  - Thiazolidinediones enhance skeletal muscle triacylglycerol synthesis while
      protecting against fatty acid-induced inflammation and insulin resistance.
AB  - In the present investigation, we studied the effects of thiazolidinedione (TZD)
      treatment on insulin-stimulated fatty acid (FA) and glucose kinetics in perfused
      muscle from high-fat (HF)-fed rats. We tested the hypothesis that TZDs prevent FA
      induced insulin resistance by attenuating proinflammatory signaling independently
      of myocellular lipid levels. Male Wistar rats were assigned to one of three 3-wk
      dietary groups: control chow fed (CON), 65% HF diet (HFD), or TZD- (troglitazone
      or rosiglitazone) enriched HF diet (TZD + HFD). TZD treatment led to a
      significant increase in plasma membrane content of CD36 protein in muscle (red: P
      = 0.01, and white: P = 0.001) that correlated with increased FA uptake (45%, P =
      0.002) and triacylglycerol (TG) synthesis (46%, P = 0.03) during the perfusion.
      Importantly, whereas HF feeding caused increased basal TG (P = 0.047),
      diacylglycerol (P = 0.002), and ceramide (P = 0.01) levels, TZD treatment only
      prevented the increase in muscle ceramide. In contrast, all of the muscle
      inflammatory markers altered by HF feeding ( upward arrowNIK protein content, P =
      0.009; upward arrowIKKbeta activity, P = 0.006; downward arrowIkappaB-alpha
      protein, P = 0.03; and upward arrowJNK phosphorylation, P = 0.003) were
      completely normalized by TZD treatment. Consistent with this, HFD-induced
      decrements in insulin action were also prevented by TZD treatment. Thus our
      findings support the notion that TZD treatment causes increased FA uptake and TG
      accumulation in skeletal muscle under insulin-stimulated conditions. Despite
      this, TZDs suppress the inflammatory response to dietary lipid overload, and it
      is this mechanism that correlates strongly with insulin sensitivity.

PMID- 17003247
TI  - Applying projective techniques to formative research in health communication
      development.
AB  - This article describes a new approach to formative research in which projective
      techniques commonly used in psychological assessment were adapted for use in
      focus groups to help design colorectal-cancer screening materials for African
      American men and women. Participants (N = 20) were divided into six "design
      teams." Each team was given a selection of design supplies and asked to create
      and discuss a visual layout for screening materials. Participants chose design
      elements that reflected visual preferences that they felt would connect
      meaningfully with other African Americans. The dynamics within the design teams
      were different than in traditional focus groups, with participants having more
      control over the group's direction. Using projective techniques helped draw out
      unique information from participants by allowing them to "project" their opinions
      onto objects. This approach may be a valuable tool for health-promotion and
      health-communication practitioners seeking insight on the implicit values of a
      priority population.

PMID- 17003248
TI  - Broadcasting behavior change: a comparison of the effectiveness of paid and
      unpaid media to increase folic acid awareness, knowledge, and consumption among
      Hispanic women of childbearing age.
AB  - Awareness about folic acid's effectiveness in reducing the risk of certain birth
      defects has increased among women in the United States; however, few Hispanic
      women are consuming enough folic acid daily. A 1998 survey conducted by the
      Gallup Organization for the National March of Dimes Birth Defects Foundation
      found that English-speaking Hispanic women had lower folic acid awareness (53%
      vs. 72%) and lower daily consumption (29% vs. 33%) than non-Hispanic White women.
      In 1999, the Centers for Disease Control and Prevention (CDC) conducted baseline
      surveys with Spanish-speaking Hispanic women in selected U.S. markets to measure
      folic acid awareness, knowledge, and consumption. A Spanish-language public
      service announcement (PSA) volunteer campaign and a paid Spanish-language media
      and community education campaign were conducted in 2000 and 2002, respectively.
      Comparisons of postcampaign surveys indicate that the paid media campaign was
      significantly more effective than the PSA campaign in increasing folic acid
      awareness, knowledge, and consumption among Spanish-speaking Hispanic women.

PMID- 17003249
TI  - Effect of dopamine on vascular reactivity in near-term lamb carotids: role of the
      endothelium.
AB  - Many neonates are diagnosed with hypotension in the first 24 hr of life. Those
      with severe hypotension are often given high doses of dopamine at 10 to 20
      microg/kg/min. This study examined the hypothesis that dopamine, a vasoactive
      drug commonly used in the neonatal intensive care unit, alters vascular
      reactivity. Vascular reactivity was measured by comparing 5HT dose-response
      characteristics in untreated near-term lamb common carotid arteries and arteries
      treated with 15 microg/kg/min of dopamine. The authors found that dopamine
      pretreatment for 60 min significantly potentiated 5HT-induced contractile tone by
      approximately 100% ( p < .05). This observed increase in tone was accompanied by
      a significant decrease in the affinity of 5HT to its receptor ( p < .05),
      suggesting an activation of a separate contractile pathway, or a mechanism
      downstream from agonist-receptor binding. Interestingly, an increase in
      contractility was observed only in endothelium-intact arteries. In arteries with
      denuded endothelium, dopamine pretreatment resulted in a small but significant
      decrease in tone compared to control arteries ( p < .05), suggesting a
      vasodilatory mechanism unmasked by endothelium removal. Although multiple
      mechanisms can increase vascular resistance, these data described the in vitro
      effects of high doses of dopamine on vascular tone as well as the role of the
      endothelium in dopaminemediated vasoconstriction.

PMID- 17003250
TI  - Smoking hygiene: reducing infant exposure to tobacco.
AB  - The American Academy of Pediatrics recently removed nicotine from the list of
      drugs contraindicated during breastfeeding. The objective of this study was to
      evaluate the feasibility of determining the effect of a smoking hygiene
      intervention on infants of breastfeeding mothers who smoke cigarettes. An
      experimental design with repeated measures was used. A convenience sample of 35
      mother-infant dyads from seven sites was recruited and randomly assigned to the
      intervention or control group. Of the 27 dyads completing the study, 16 were in
      the experimental group and 11 were in the control group. Smoking hygiene was
      introduced when infants were 2 weeks old and reinforced when they were 3 and 5
      weeks old. At these three data points, infant health and urinary nicotine and
      cotinine levels were measured, as well as the mothers' breast-milk nicotine and
      cotinine levels and smoking hygiene behaviors. Recruiting and retaining a sample
      of breastfeeding mothers who smoke proved difficult. Only 27% of women in the
      intervention group implemented all aspects of the smoking hygiene intervention
      behaviors. Repeated-measures ANOVA revealed no difference in a) infant urinary
      nicotine and cotinine levels or b) breast-milk nicotine and cotinine levels
      between the two groups. The McNemar test for related samples revealed no
      difference between frequency of respiratory symptoms in either the control or
      intervention groups when Week 2 levels were compared with levels at Weeks 3 and
      5. Mothers were not successful in adhering to the smoking hygiene intervention.
      To adequately test interventions, strategies must be developed to help women
      incorporate health-promoting behaviors into their lives.

PMID- 17003251
TI  - Multiple gestation: side effects of antepartum bed rest.
AB  - The birth rate for higher order multiples has dramatically increased in recent
      decades. Multiple gestation pregnancies are considered to be at high obstetric
      risk. Antepartum bed rest is often prescribed to offset complications despite the
      lack of evidence for its effectiveness in preventing complications. This
      longitudinal repeated-measures study identified side effects of antepartum bed
      rest treatment for 31 hospitalized women with twin or triplet gestation. Maternal
      weight gain and infant birth weight were recorded. Antepartum stressors were
      measured by the Antepartum Stressors Hospital Inventory, and depressive symptoms
      were measured by the Center for Epidemiologic Studies Depression Scale (CES-D).
      Antepartum and post-partum side effects of bed rest were also assessed by the
      Antepartum and Postpartum Symptom Checklists. The weekly rate of maternal weight
      gain during hospitalization was significantly less than recent recommendations
      for multiple gestation weight gain (t = - 2.14, p = .04). Infant birth weights
      were appropriate for gestational age. There were fewer than expected small-for
      gestational-age infants. Concerns regarding family status and separation from
      family were the major antepartum stressors. Women reported a high number of
      symptoms during bed rest (M = 22), which did not significantly change across 2
      weeks. CES-D scores for depressive symptoms were high on antepartum hospital
      admission. Postpartum symptoms were initially high but had significantly declined
      by 6 weeks: F(1, 27) = 15.68, p = .00. These findings suggest that interventions
      are needed to reduce antepartum maternal weight loss, stress, physiologic and
      psychosocial symptoms, and depressive symptoms, as well as reduce postpartum
      symptoms of maternal morbidity.

PMID- 17003252
TI  - Quality of life improves after renal artery stenting.
AB  - Although treatment of renal artery stenosis (RAS) with stents has been shown to
      improve blood pressure (BP) and renal function in some patients, little is known
      about the effect on health-related quality of life. A composite quality of life
      survey was administered in a cross-sectional cohort fashion to 149 patients
      presenting with angiographically and hemodynamically confirmed RAS either before
      (baseline, n = 37) or after (follow-up, n = 112) stent revascularization. BP,
      renal function, and antihypertensive medication use were also assessed. Systolic
      BP was lower in the revascularized patients (166 +/- 23 vs. 153 +/- 26, p < .01).
      The Short Form-36 Physical Component Summary (PCS) scores were higher (better) in
      revascularized patients (37 +/- 9 vs. 31 +/- 9, p < .01), whereas Mental
      Component Summary scores were equivalent (49 +/- 13 vs. 51 +/- 11, p = ns). Sleep
      dysfunction scores were lower (better) in the revascularized patients (32 +/- 26
      vs. 48 +/- 32, p < .001), whereas self-reported appetite was higher (better; 62%
      +/- 29% vs. 73% +/- 27%,p < .05). After matching for age and gender, Short Form
      36 PCS remained higher in the revascularized cohort (37 +/- 8 vs. 32 +/- 8, p <
      .05). Importantly, in multivariate analysis, revascularization was the most
      significant determinant of a higher PCS score (r2 = .07, beta = 5.21, p < .01).
      The current data suggest that renal artery stenting may improve health-related
      quality of life in patients with renovascular disease.

PMID- 17003253
TI  - Thermal thresholds and catastrophizing in individuals with chronic pain after
      whiplash injury.
AB  - Thermal sensitivity, thermal pain thresholds, and catastrophizing were examined
      in individuals with whiplash associated disorders (WAD) and in healthy pain-free
      participants. Quantitative sensory testing (QST) was used to measure skin
      sensitivity to cold and warmth and cold and heat pain thresholds over both the
      thenar eminence and the trapezius muscle (TrM) in 17 participants with WAD (age
      50.8 +/- 11.3 years) and 18 healthy participants (age 44.8 +/- 10.2 years). The
      Pain Catastrophizing Scale (PCS) was used to determine pain coping strategies,
      and visual analogue scales were used for self-assessment of current background
      pain in individuals in the WAD group as well as experienced pain intensity and
      unpleasantness after QST and sleep quality in all participants. There were
      significant differences in warmth threshold and cold and heat pain thresholds of
      the TrM site between the WAD and pain-free groups. Significant differences
      between the two groups were also found for the catastrophizing dimension of
      helplessness in the PCS and in self-assessed quality of sleep. A correlational
      analysis showed that current background pain is significantly correlated with
      both cold discrimination and cold pain threshold in the skin over the TrM in
      individuals with WAD. These findings imply that thermal sensitivity is an
      important factor to consider in providing nursing care to individuals with WAD.
      Because biopsychosocial factors also influence the experience of pain in
      individuals with WAD, the role of nurses includes not only the description of the
      pain phenomenon but also the identification of relieving and aggravating factors.

PMID- 17003254
TI  - Genetics of von Willebrand disease type 1.
AB  - The most common form of von Willebrand disease (VWD) is reported to be type 1,
      accounting for as much as 80% of reported cases. With prevalence estimates as
      high as 1.6% in the general population, upwards of 4.5 million Americans may be
      affected. Unfortunately, VWD type 1 is also the most difficult type to diagnose.
      Despite the continuing progress in defining the genetic lesions responsible for
      VWD types 2 and 3, identification of the genetic determinants of VWD type 1
      remains elusive. Herein the phenomenon known as VWD is summarized, the challenges
      associated with the diagnosis of type 1 VWD are described, and the role of
      genetic research in meeting these challenges is explored. The authors identify
      key gaps in the current genetics literature and suggest new avenues for future
      research. Lastly, they explore the role of nurses in this research and clinical
      endeavor. To the authors'knowledge, this review is the first to address these
      complex issues in nursing research.

PMID- 17003255
TI  - The cancer chemotherapy drug etoposide (VP-16) induces proinflammatory cytokine
      production and sickness behavior-like symptoms in a mouse model of cancer
      chemotherapy-related symptoms.
AB  - Cancer chemotherapy-related symptoms such as fatigue, malaise, loss of interest
      in social activities, difficulty concentrating, and changes in sleep patterns can
      lead to treatment delays, dose reductions, or termination and have a profound
      effect on the physical, psychosocial, and economic aspects of quality of life.
      Clinicians have long suspected that these symptoms are similar to those
      associated with "sickness behavior," which is triggered by the production of the
      inflammatory cytokines IL-1beta, TNF-alpha, and IL-6 by macrophages and other
      cells of the innate immune system in response to immune challenge. The p38
      mitogen-activated protein kinase (p38 MAPK) plays a central role in the
      production of these cytokines and consequently the induction of sickness
      behavior. Several cancer chemotherapy drugs have been shown to activate p38 MAPK,
      but whether these drugs can also induce the production of inflammatory cytokines
      to cause sickness behavior is unknown. The aim of this study was to determine
      whether the cancer chemotherapy drug etoposide (VP-16), which is known to
      activate p38 MAPK, could induce inflammatory cytokine production by murine
      macrophages and sickness-like behaviors when injected into mice. VP-16 activated
      p38 MAPK and induced IL-6 production in murine macrophages in a p38 MAPK-
      dependent manner. VP-16 administration rapidly increased serum levels of IL-6 in
      healthy mice and induced sickness-like behaviors as evidenced by a decrease in
      food intake, body weight, hemoglobin level, and voluntary wheel-running activity.
      These findings support the idea that the induction of IL-1beta, TNF-alpha, and IL
      6 by cancer chemotherapy drugs underlies the fatigue and associated symptoms
      experienced by people undergoing cancer chemotherapy.

PMID- 17003256
TI  - Involvement of calpain and synaptotagmin Ca2+ sensors in hormone secretion from
      excitable endocrine cells.
AB  - The requirement for Ca(2+) to regulate hormone secretion from endocrine cells is
      long established, but the precise function of Ca(2+) sensors in stimulus
      secretion coupling remains unclear. In the current study, we examined the
      expression of calpain and synaptotagmin in INS-1 pancreatic and GH3 and AtT20
      pituitary cells, and investigated the sensitivity of hormone secretion from these
      cells to inhibition of the calpain family of cysteine proteases. Little
      difference in expression of mu-calpain was observed between the different
      endocrine cells. However, AtT20 cells did exhibit an extremely low abundance of
      both m-calpain and the 54 kDa isoform of calpain-10 relative to their expression
      in INS-1 and GH3 cells. Interestingly, secretagog-stimulated secretion from both
      INS-1 and GH3 cells was completely abolished following pre-incubation with the
      cysteine protease inhibitor E64, whereas stimulated secretion from AtT20 cells
      was modest and completely insensitive to E64 inhibition. These results are in
      stark contrast to synaptotagmin data. Synaptotagmin expression in AtT20 cells is
      abundant, whereas INS-1 cells express extremely low levels of this Ca(2+) sensor,
      relative to the pituitary cells. We hypothesize that the expression pattern of
      calpain and synaptotagmin isoforms may reflect alternative mechanisms of stimulus
      secretion coupling in excitable endocrine cells.

PMID- 17003257
TI  - The neuroendocrine system of invertebrates: a developmental and evolutionary
      perspective.
AB  - Neuroendocrine control mechanisms are observed in all animals that possess a
      nervous system. Recent analyses of neuroendocrine functions in invertebrate model
      systems reveal a great degree of similarity between phyla as far apart as
      nematodes, arthropods, and chordates. Developmental studies that emphasize the
      comparison between different animal groups will help to shed light on questions
      regarding the evolutionary origin and possible homologies between neuroendocrine
      systems. This review intends to provide a brief overview of invertebrate
      neuroendocrine systems and to discuss aspects of their development that appear to
      be conserved between insects and vertebrates.

PMID- 17003258
TI  - Circulating hormones and hypothalamic energy balance: regulatory gene expression
      in the Lou/C and Wistar rats.
AB  - To ascertain the mechanisms underlying low caloric intake and low body weight in
      the Lou/C rat, the circulating hormone levels and gene expression of hypothalamic
      peptides and receptors important in energy balance and the induction of
      suppressor of cytokine signalling 3 (SOCS3) gene expression in response to leptin
      challenge were compared with Wistar rats. Plasma leptin levels were lower in the
      Lou/C rat, as were levels of rat corticosterone, TSH and T4 but not T3. Ghrelin
      levels were higher in the Lou/C rat. Total leptin receptor (Ob-R) and the long
      form of the leptin receptor (Ob-Rb) gene expression were lower in the arcuate
      (ARC) and ventromedial nuclei (VMN) in Lou/C rat. Ghrelin receptor expression in
      the ARC and VMN was lower in Lou/C than in Wistar rats. However, agouti gene
      related peptide (AgRP) and neuropeptide Y (NPY) gene expression were higher in
      the Lou/C rat. There was no difference in the level of cocaine- and amphetamine
      regulated transcript gene expression in the ARC, but both were higher in the
      paraventricular nuclei of the Lou/C breed. There was no difference in Ob-R gene
      expression in, or [(125)I]leptin binding to, the choroid plexus. SOCS3 mRNA
      induction in response to leptin was lower in the Lou/C rat. This study reveals
      that the comparatively low plasma leptin, TSH and T4 levels, and high ghrelin
      levels together with high levels of AgRP and NPY gene expression seen in the
      Lou/C rat are indicative of a strong drive to eat and decreased energy
      expenditure, which are in direct opposition to the comparatively low body weight
      and adiposity of this rat strain.

PMID- 17003259
TI  - Serotonin stimulates GnRH secretion through the c-Src-PLC gamma1 pathway in GT1-7
      hypothalamic cells.
AB  - Serotonin is a neurotransmitter that alters the hypothalamic-pituitary-adrenal
      axis. To date, however, the molecular mechanisms underlying the role of serotonin
      in hormone secretion have remained largely unclear. In this study, we report that
      serotonin activates phospholipase C (PLC) gamma1 in an Src-dependent manner in
      hypothalamic GT1-7 cells, and that pretreatment with either 4-amino-5-(4
      chlorophenyl)-7-(t-butyl) pyrazole [3, 4-d] pyrimidine, an Src-kinase inhibitor,
      or U73122, a PLC inhibitor, attenuates the serotonin-induced increase in calcium
      levels. Also, PLC gamma1 binds to c-Src through the Src-homology (SH) 223 domain
      upon serotonin treatment. Moreover, calcium increase is alleviated in the cells
      transientlyexpressing SH223 domain-deleted PLC gamma1 or lipase inactive mutant
      PLC gamma1, as compared with cells transfected with wild-type PLC gamma1.
      Furthermore, the inhibition of the activities of either PLC or Src results in a
      significant diminution of the serotonin-induced release of gonadotropin-releasing
      hormone (GnRH). In addition, the results of our small-interfering RNA experiment
      confirm that endogenous PLC gamma1 is a prerequisite for serotonin-mediated
      signaling pathways. Taken together, our findings demonstrate that serotonin
      stimulates the release of GnRH through the Src-PLC gamma1 pathway, via the
      modulation of intracellular calcium levels.

PMID- 17003260
TI  - Temporal expression of estrogen receptor alpha in the hypothalamus and medulla
      oblongata during fasting: a role of noradrenergic neurons.
AB  - Fasting-induced LH suppression is augmented by estrogen in female rats. We
      investigated the temporal changes in the number of estrogen receptor alpha
      (ERalpha)-immunoreactive (ir) cells in various brain regions in ovariectomized
      rats fasted for 6, 24, 30, and 48 h, commencing at 1300 h. We also determined the
      anatomical relationship of ERalpha immunoreactivity and dopamine-beta-hydroxylase
      (DBH) neurons in the A2 region of the nucleus of the solitary tract (NTS) and the
      paraventricular nucleus (PVN). The number of ERalpha-ir cells significantly
      increased after 30 h from the onset of fasting in the PVN and NTS compared with
      the unfasted controls and was sustained until 48 h. In the A2 region of 48-h
      fasted rats, 46.75% DBH-ir cells expressed ERalpha, and this was significantly
      higher than in unfasted controls (8.16% DBH-ir cells expressed ERalpha). In the
      PVN, most ERalpha-ir neurons were juxtaposed with DBH-ir varicosities. These
      results suggest that ERalpha is expressed in specific brain regions at a defined
      time from the onset of fasting. In addition, the anatomical relationship of
      noradrenergic and ERalpha-ir neurons in the A2 region and PVN may suggest a role
      for estrogen in increasing the activity of noradrenergic neurons in the A2 region
      and enhancing sensitivity of the PVN to noradrenergic input arising from the
      lower brainstem and thereby augmenting the suppression of LH secretion during
      fasting.

PMID- 17003261
TI  - Plasma profiles of adrenocorticotropic hormone, cortisol, alpha-melanocyte
      stimulating hormone, and growth hormone in dogs with pituitary-dependent
      hyperadrenocorticism before and after hypophysectomy.
AB  - The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, alpha
      melanocyte-stimulating hormone (alpha-MSH), and GH were studied in 17 dogs with
      pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy.
      The aim of the study was to investigate the relation between the hormone profile
      characteristics and recurrence of PDH after surgery. The hormones were secreted
      in a pulsatile fashion. The basal plasma cortisol concentration and area under
      the curve (AUC) for cortisol were significantly higher in the PDH cases than in
      eight controls. The characteristics of the plasma profiles of ACTH and alpha-MSH
      were not significantly different between the PDH cases and the controls. In the
      PDH cases, less GH was secreted in pulses than in the controls, but the
      difference was not significant. The basal plasma cortisol concentration, the AUC
      for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased
      significantly after hypophysectomy for the group of PDH cases. The basal plasma
      concentrations of ACTH and alpha-MSH, the AUC for alpha-MSH, and the
      characteristics of the plasma GH profiles of the PDH cases remained unchanged
      after hypophysectomy. No pulses of alpha-MSH were observed after hypophysectomy.
      The co-occurrence between the ACTH and cortisol pulses decreased significantly
      with hypophysectomy. The postoperative pulse frequency of ACTH was the only
      characteristic with predictive value for the recurrence of PDH after
      hypophysectomy. The results of this study demonstrate that ACTH, cortisol, alpha
      MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy
      effectively reduces the secretion of ACTH and cortisol. The presence of ACTH
      pulses after hypophysectomy is a risk factor for the recurrence of
      hyperadrenocorticism.

PMID- 17003262
TI  - GH in the dwarf dopaminergic D2 receptor knockout mouse: somatotrope population,
      GH release, and responsiveness to GH-releasing factors and somatostatin.
AB  - Recently, the importance of the dopaminergic D2 receptor (D2R) subtype in normal
      body growth and neonatal GH secretion has been highlighted. Disruption of D2R
      alters the GHRH-GH-IGF-I axis and impairs body growth in adult male mice. The D2R
      knockout (KO) dwarf mouse has not been well characterized; we therefore sought to
      determine somatotrope function in the adult pituitary. Using immunohistochemistry
      and confocal microscopy, we found a significant decrease in the somatotrope
      population in pituitaries from KO mice (P=0.043), which was paralleled by a
      decreased GH output from pituitary cells cultured in vitro. In cells from adult
      mice the response amplitude to GHRH differed between genotypes (lower in KO), but
      this difference was less dramatic after taking into account the lower basal
      release and hormone content in the KO cells. Furthermore, there were no
      significant differences in cAMP generation in response to GHRH between genotypes.
      By Western blot, GHRH-receptor in pituitary membranes from KO mice was reduced to
      46% of the level found in wildtype (WT) mice (P=0.016). Somatostatin induced a
      concentration-dependent decrease in GH and prolactin (PRL) secretion in both
      genotypes, and 1x10(-7) M ghrelin released GH in cells from both genotypes
      (P=0.017) in a proportionate manner to basal levels. These results suggest that
      KO somatotropes maintain a regulated secretory function. Finally, we tested the
      direct effect of dopamine on GH and PRL secretion in cells from both genotypes at
      20 days and 6 months of life. As expected, we found that dopamine could reduce
      PRL levels at both ages in WT mice but not in KO mice, but there was no
      consistent effect of the neurotransmitter on GH release in either genotype at the
      ages studied. The present study demonstrates that in the adult male D2R KO mouse,
      there is a reduction in pituitary GH content and secretory activity. Our results
      point to an involvement of D2R signaling at the hypothalamic level as dopamine
      did not release GH acting at the pituitary level either in 1-month-old or adult
      mice. The similarity of the pituitary defect in the D2R KO mouse to that of GHRH
      deficient models suggests a probable mechanism. A loss of dopamine signaling via
      hypothalamic D2Rs at a critical age causes the reduced release of GHRH from
      hypophyseotropic neurons leading to inadequate clonal expansion of the
      somatotrope population. Our data also reveal that somatotrope cell number is much
      more sensitive to changes in neonatal GHRH input than their capacity to develop
      properly regulated GH-secretory function.

PMID- 17003263
TI  - UbcH7 interacts with the glucocorticoid receptor and mediates receptor
      autoregulation.
AB  - Unlike other nuclear receptors, transactivation by the glucocorticoid receptor
      (GR) is increased by the inhibition of the ubiquitin/proteasome pathway. Here, we
      demonstrate that the ubiquitin-conjugating enzyme (E2), UbcH7, physically
      interacts with the GR and, when overexpressed, reduces the ability of the
      receptor to upregulate gene expression. Chemical inhibition of the 26S proteasome
      abolished the downregulation effect of overexpressed UbcH7, suggesting a role for
      the 26S proteasome, and GR protein stability in mediating the UbcH7 effect.
      Furthermore, a UbcH7 dominant negative mutant (C89S), unable to transfer
      ubiquitin, failed to repress GR transactivation. Indeed, overexpression of the
      mutant UbcH7 was sufficient to augment GR transactivation to levels achieved
      using the proteasome inhibitor MG132, but there was no further induction when
      MG132 and the UbcH7 mutant were used together. Expression of the dominant
      negative UbcH7 abolished ligand-dependent downregulation of GR protein,
      suggesting that the UbcH7 effect was mediated by regulation of GR protein
      concentration. Taken together, these data show that UbcH7 is a key regulator of
      GR turnover and glucocorticoid sensitivity.

PMID- 17003264
TI  - Influence of porcine genotype on the abundance of thyroid hormones and leptin in
      sow milk and its impact on growth, metabolism and expression of key adipose
      tissue genes in offspring.
AB  - Neonatal mortality is greater in commercial porcine genotypes, compared with the
      ancient Meishan breed that rapidly lay down adipose tissue; this may be related
      to hormones, such as triiodothyronine (T(3)) or leptin. Leptin is present in
      maternal milk; however, the extent to which this supply provides the neonate with
      leptin is unknown, but may play a role in growth and development. We investigated
      whether thyroid hormones and leptin concentrations in maternal milk differed
      between genotypes; and whether this influenced piglet concentrations or
      expression of genes involved in adipose tissue regulation. Eight Meishan and six
      commercial sows were entered into the study and milk samples from the day of
      parturition to day 4 postpartum was taken daily. The median birth weight piglet
      in each litter had a daily venous blood sample taken and was euthanised on day 4.
      Gene expressions of IGF-I, IGF-binding protein 3 (IGFBP-3), peroxisome
      proliferators activated receptor (PPAR)gamma and glucocorticoid receptor (GR)
      were measured in adipose tissue using real-time PCR. T(3) was increased in
      Meishan milk, but not in piglet plasma. Milk thyroxine was similar between breeds
      but commercial piglet levels were significantly higher. Leptin was higher in
      commercial sow milk throughout the study. Milk leptin was strongly correlated to
      plasma leptin during the first postnatal days and also to organ and body weight
      in Meishan piglets that also had significantly higher expression of GR, but not
      IGF-I, IGFBP-3 or PPARgamma. In conclusion, we have found a significant disparity
      in the provision of thyroid hormones in Meishan and commercial sow's milk. These
      changes are not always translated to plasma concentrations of hormone in the
      piglet. Leptin appears to have a stronger role in growth and development in the
      Meishan genotype compared with commercial; along with the increased GR
      expression, this may also represent a potential mechanism behind the rapid
      accumulation of adipose tissue in Meishan piglets.

PMID- 17003265
TI  - The sarcoplasmic-endoplasmic reticulum Ca2+ ATPase 2b regulates the Ca2+
      transients elicited by P2Y2 activation in PC Cl3 thyroid cells.
AB  - In PC Cl3 cells, a continuous, fully differentiated rat thyroid cell line, P2Y(2)
      purinoceptor activation provoked a transient increase of [Ca(2+)](i), followed by
      a decreasing sustained phase. The alpha and beta1 protein kinase C (PKC)
      inhibitor Go6976 decreased the rate of decrement to the basal [Ca(2+)](i) level
      and increased the peak of Ca(2+) entry of the P2Y(2)-provoked Ca(2+)transients.
      These effects of Go 6976 were not caused by an increased permeability of the
      plasma membrane, since the Mn(2+) and Ba(2+) uptake were not changed by Go 6976.
      Similarly, the Na(+)/Ca(2+) exchanger was not implicated, since the rate of
      decrement to the basal [Ca(2+)](i) level was equally decreased in physiological
      and Na(+)-free buffers, in the presence of Go 6976. On the contrary, the activity
      of the sarcoplasmic-endoplasmic reticulum Ca(2+)ATPase (SERCA) 2b was profoundly
      affected by Go 6976 since the drug was able to completely inhibit the stimulation
      of the SERCA 2b activity elicited by P2-purinergic agonists. Finally, the PKC
      activator phorbol myristate acetate had effects opposite to Go 6976, in that it
      markedly increased the rate of decrement to the basal [Ca(2+)](i) level after
      P2Y(2) stimulation and also increased the activity of SERCA 2b. These results
      suggest that SERCA 2b plays a role in regulating the sustained phase of Ca(2+)
      transients caused by P2Y(2) stimulation.

PMID- 17003266
TI  - Oral administration of glucose promotes intracellular partitioning of fatty acid
      toward storage in white but not in red muscle.
AB  - Lipid accumulation in non-adipose tissues is strongly associated with the
      metabolic syndrome, possibly due to aberrant partitioning of intracellular fatty
      acids between storage and oxidation. In the present study, we administered the
      non-metabolizable fatty acid analog [9,10-(3)H]-(R)-2-bromopalmitate, and
      authentic (14)C-palmitate to conscious rats, in order to directly examine the
      initial intracellular fate of fatty acids in a range of insulin-sensitive
      tissues, including white and red muscles, liver, white adipose tissue, and heart.
      Rats were studied after administration of an oral glucose load to examine the
      effect of physiological elevation of glucose and insulin. The tracer results
      showed that glucose administration partitioned fatty acid toward storage in white
      muscle (storage:uptake ratios, vehicle vs glucose; 0.64 +/- 0.02 vs 0.92 +/-
      0.09, P < 0.05), and in liver (0.66 +/- 0.07 vs 0.98 +/- 0.04, P < 0.05), but not
      in red muscle (1.18 +/- 0.07 vs 1.36 +/- 0.11, P = not significant). These
      results demonstrate the physiological relevance of the so-called 'reverse' Randle
      cycle, but surprisingly show that it may be more important in white rather than
      oxidative red muscle.

PMID- 17003267
TI  - Endogenous islet uncoupling protein-2 expression and loss of glucose homeostasis
      in ob/ob mice.
AB  - We hypothesized that the loss of glucose homeostasis in ob/ob mice is associated
      with upregulation of islet uncoupling protein-2 (UCP2) expression, leading to
      impaired glucose-stimulated insulin secretion (GSIS). Changes in glucose
      homeostasis in lean and ob/ob mice from 5 to 16 weeks were assessed by fasting
      blood glucose, plasma insulin, oral glucose tolerance, and tissue insulin
      sensitivity. In vitro GSIS and ATP content were assayed in isolated islets, while
      UCP2 expression was determined by quantitative real-time PCR and immunoblotting.
      Short-term reduction of UCP2 expression was achieved through transfection of
      islets with specific small interfering RNA. Insulin resistance was detected in 5
      week-old ob/ob mice, but GSIS and blood glucose levels remained normal. By 8
      weeks of age, ob/ob mice displayed fasting hyperglycemia, hyperinsulinemia and
      glucose intolerance, and also had elevated non-esterified fatty acid
      concentration in plasma. In vitro, GSIS and ATP generation were impaired in ob/ob
      islets. Islet UCP2 expression was elevated at 5 and 8 weeks of age. Short-term
      knockdown of islet UCP2 increased GSIS in islets of lean mice, but had no effect
      in islets from ob/ob mice. Loss of glucose homeostasis and impairment of insulin
      secretion from isolated islets at 8 weeks in ob/ob mice is preceded by an
      increase in UCP2 expression in islets. Moreover, the glucolipotoxic conditions
      observed are predicted to increase UCP2 activity, contributing to lower islet ATP
      and GSIS.

PMID- 17003268
TI  - cAMP-mediated signaling normalizes glucose-stimulated insulin secretion in
      uncoupling protein-2 overexpressing beta-cells.
AB  - We investigated whether an increase in cAMP could normalize glucose-stimulated
      insulin secretion (GSIS) in uncoupling protein-2 (UCP2) overexpressing (ucp2-OE)
      beta-cells. Indices of beta-cell (beta-TC-6f7 cells and rodent islets) function
      were measured after induction of ucp2, in the presence or absence of cAMP
      stimulating agents, analogs, or inhibitors. Islets of ob/ob mice had improved
      glucose-responsiveness in the presence of forskolin. Rat islets overexpressing
      ucp2 had significantly lower GSIS than controls. Acutely, the protein kinase A
      (PKA) and epac pathway stimulant forskolin normalized insulin secretion in ucp2
      OE rat islets and beta-TC-6f7 beta-cells, an effect blocked by specific PKA
      inhibitors but not mimicked by epac agonists. However, there was no effect of
      ucp2-OE on cAMP concentrations or PKA activity. In ucp2-OE islets, forskolin
      inhibited ATP-dependent potassium (K(ATP)) channel currents and (86)Rb(+) efflux,
      indicative of K(ATP) block. Likewise, forskolin application increased
      intracellular Ca(2+), which could account for its stimulatory effects on insulin
      secretion. Chronic exposure to forskolin increased ucp2 mRNA and exaggerated
      basal secretion but not GSIS. In mice deficient in UCP2, there was no
      augmentation of either cAMP content or cAMP-dependent insulin secretion. Thus,
      elevating cellular cAMP can reverse the deficiency in GSIS invoked by ucp2-OE, at
      least partly through PKA-mediated effects on the K(ATP) channel.

PMID- 17003269
TI  - Nitric oxide inhibits, and carbon monoxide activates, islet acid alpha-glucoside
      hydrolase activities in parallel with glucose-stimulated insulin secretion.
AB  - We have studied the influence of nitric oxide (NO) and carbon monoxide (CO),
      putative messenger molecules in the brain as well as in the islets of Langerhans,
      on glucose-stimulated insulin secretion and on the activities of the acid alpha
      glucoside hydrolases, enzymes which we previously have shown to be implicated in
      the insulin release process. We have shown here that exogenous NO gas inhibits,
      while CO gas amplifies glucose-stimulated insulin secretion in intact mouse
      islets concomitant with a marked inhibition (NO) and a marked activation (CO) of
      the activities of the lysosomal/vacuolar enzymes acid glucan-1,4-alpha
      glucosidase and acid alpha-glucosidase (acid alpha-glucoside hydrolases).
      Furthermore, CO dose-dependently potentiated glucose-stimulated insulin secretion
      in the range 0.1-1000 microM. In intact islets, the heme oxygenase substrate
      hemin markedly amplified glucose-stimulated insulin release, an effect which was
      accompanied by an increased activity of the acid alpha-glucoside hydrolases.
      These effects were partially suppressed by the guanylate cyclase inhibitor 1H
      [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Hemin also inhibited inducible NO
      synthase (iNOS)-derived NO production probably through a direct effect of CO on
      the NOS enzyme. Further, exogenous CO raised the content of both cGMP and cAMP in
      parallel with a marked amplification of glucose-stimulated insulin release, while
      exogenous NO suppressed insulin release and cAMP, leaving cGMP unaffected.
      Emiglitate, a selective inhibitor of alpha-glucoside hydrolase activities, was
      able to markedly inhibit the stimulatory effect of exogenous CO on both glucose
      stimulated insulin secretion and the activityof acid glucan-1,4-alpha-glucosidase
      and acid alpha-glucosidase, while no appreciable effect on the activities of
      other lysosomal enzyme activities measured was found. We propose that CO and NO,
      both produced in significant quantities in the islets of Langerhans, have
      interacting regulatory roles on glucose-stimulated insulin secretion. This
      regulation is, at least in part, transduced through the activity of cGMP and the
      lysosomal/vacuolar system and the associated acid alpha-glucoside hydrolases, but
      probably also through a direct effect on the cAMP system.

PMID- 17003270
TI  - Direct and indirect effects of insulin on hepatic glucose production in diabetic
      depancreatized dogs during euglycemia.
AB  - Insulin suppresses glucose production (GP) via both extrahepatic (indirect) and
      hepatic (direct) effects. We have shown that the direct effect, undetectable in
      moderately hyperglycemic diabetic dogs, is restored by insulin-induced
      euglycemia. The first aim of the present study was to determine whether
      euglycemia per se, and not the excess insulin needed to obtain it, restores the
      direct effect of insulin on GP. Basal insulin was given portally in
      depancreatized dogs to attain only moderate hyperglycemia, then an additional
      insulin was given portally or peripherally to match the peripheral insulin levels
      and thus to obtain a greater hepatic insulinization with portal delivery. Plasma
      glucose was allowed to fall to euglycemia before a euglycemic clamp was
      performed. During euglycemia, there was a tendency (P=0.075) for greater
      suppression of GP by portal than peripheral insulin. Also, there was a
      significantly different effect of time (P=0.01) on GP in the two groups, with
      greater suppression over time in the portal group. The second aim was to test the
      hypothesis that because of inadequate hepatic insulinization and consequent lack
      of direct inhibition of GP, peripheral insulin replacement requires peripheral
      hyperinsulinemia to achieve euglycemia. Portal or peripheral insulin was given to
      achieve euglycemia and basal GP, and insulin levels were measured. More
      peripheral insulinemia was required with peripheral than portal insulin
      replacement to maintain similar euglycemia and GP. Our conclusions are as
      follows: (1) euglycemia per se is sufficient to acutely restore the direct effect
      of insulin on GP and (2) at euglycemia, peripheral replacement of insulin, as in
      insulin-treated diabetes, results in peripheral hyperinsulinemia but unchanged
      basal GP.

PMID- 17003271
TI  - Activation of the extracellular calcium-sensing receptor initiates insulin
      secretion from human islets of Langerhans: involvement of protein kinases.
AB  - The extracellular calcium-sensing receptor (CaR) is usually associated with
      systemic Ca(2+) homeostasis, but the CaR is also expressed in many other tissues,
      including pancreatic islets of Langerhans. In the present study, we have used
      human islets and an insulin-secreting cell line (MIN6) to investigate the effects
      of CaR activation using the calcimimetic R-568, a CaR agonist that activates the
      CaR at physiological concentrations of extracellular Ca(2+). CaR activation
      initiated a marked but transient insulin secretory response from both human
      islets and MIN6 cells at a sub-stimulatory concentration of glucose, and further
      enhanced glucose-induced insulin secretion. CaR-induced insulin secretion was
      reduced by inhibitors of phospholipase C or calcium-calmodulin-dependent kinases,
      but not by a protein kinase C inhibitor. CaR activation was also associated with
      an activation of p42/44 mitogen-activated protein kinases (MAPK), and CaR-induced
      insulin secretion was reduced by an inhibitor of p42/44 MAPK activation. We
      suggest that the beta-cell CaR is activated by divalent cations co-released with
      insulin, and that this may be an important mechanism of intra-islet communication
      between beta-cells.

PMID- 17003272
TI  - Insulin and glucose mediate opposite intracellular ionized magnesium variations
      in human lymphocytes.
AB  - Insulin is capable of increasing intracellular magnesium, although very little is
      known about the effect of insulin on the biologically active fraction of
      magnesium, i.e. the ionized quota (Mg(i)(2+)), its interactions with glucose, and
      the cellular mechanisms involved in these processes. We studied the interactions
      of the effects of insulin and glucose on intracellular ionized magnesium in human
      lymphocytes. Mg(i)(2+) was measured using a fluorimetric method and the Mg(2+)
      sensitive dye, furaptra. We found that insulin significantly increases the
      Mg(i)(2+)(without insulin 227 +/- 14 microM, with 10 microU/ml, insulin 301 +/-
      30 microM, P<0.0001, n = 12) in a dose-dependent manner in all three glucose
      concentrations tested (5, 7 and 15 mmol/l). The half-maximal effect of insulin
      was approximately 0.8 microU/ml. Glucose and insulin showed opposite effects in
      their ability to modify Mg(i)(2+) in lymphocytes. Inhibitors of the membrane
      Na(+)- Mg(2+) transport system and of phosphatidylinositol (PI) 3-kinase abolish
      the insulin-mediated increase of Mg(i)(2+), thus suggesting that insulin is
      capable of increasing Mg(i)(2+) by modulating the activity of this transport
      system, possibly through the mediation of PI 3-kinase activation. Taking into
      account the relationship between insulin and glucose plasma levels and their
      opposing effects on Mg(i)(2+), this mechanism may represent the two limbs of a
      biphasic regulatory system of Mg(i)(2+) in both physiological and pathological
      conditions.

PMID- 17003273
TI  - Glutamine regulates expression of key transcription factor, signal transduction,
      metabolic gene, and protein expression in a clonal pancreatic beta-cell line.
AB  - We have investigated the effects of prolonged exposure (24 h) to the amino acid l
      glutamine, on gene and protein expression using clonal BRIN-BD11 beta-cells.
      Expression profiling of BRIN-BD11 cells was performed using oligonucleotide
      microarray analysis. Culture for 24 h with 10 mM l-glutamine compared with 1 mM
      resulted in substantial changes in gene expression with 148 genes upregulated
      more than 1.8-fold, and 18 downregulated more than 1.8-fold, including many genes
      involved in cellular signaling, metabolism, gene regulation, and the insulin
      secretory response. Subsequent functional experiments confirmed that l-glutamine
      increased the activity of the Ca(2+) regulated phosphatase calcineurin and the
      transcription factor Pdx1. Additionally, we demonstrated that beta-cell-derived l
      glutamate was released into the extracellular medium at high rates. As
      calcineurin is a regulator of the glutamate N-methyl-d-aspartate (NMDA) receptor
      activity, we investigated the action of NMDA on nutrient-induced insulin
      secretion, and demonstrated suppressed insulin release. These observations
      indicate important long-term effects of l-glutamine in regulating beta-cell gene
      expression, signaling, and secretory function.

PMID- 17003274
TI  - Islet neogenesis associated protein transgenic mice are resistant to
      hyperglycemia induced by streptozotocin.
AB  - Islet neogenesis associated protein (INGAP) is a protein factor that can
      stimulate new islet mass from adult pancreatic progenitor cells. In models of
      islet neogenesis, INGAP expression is elevated in pancreatic acinar cells. Using
      a transgenic model to drive a sustained expression of INGAP in pancreatic acinar
      cells, we have identified a protection to chemical-induced hyperglycemia. A
      sustained expression of INGAP during development did not perturb islet
      development or basal blood glucose homeostasis, although beta-cell mass and
      pancreatic insulin content were significantly increased in the INGAP transgenic
      mice. When challenged with a diabetogenic dose of streptozotocin (STZ), mice
      carrying the INGAP transgene did not become hyperglycemic. In contrast, wild-type
      mice became and remained hyperglycemic, blood glucose > 550 mg/dl. The serum
      insulin levels and islet morphology were preserved in the transgenic mice after
      STZ treatment. These data suggest that the sustained expression of INGAP in the
      acinar pancreas confers resistance to a diabetogenic insult. The INGAP transgenic
      mouse provides a new model to uncover factors that are protective to diabetes
      onset and biomarkers to track beta-cell pathology.

PMID- 17003275
TI  - Insulin resistance and increased pancreatic beta-cell proliferation in mice
      expressing a mutant insulin receptor (P1195L).
AB  - Several mutations of the tyrosine kinase domain of insulin receptor (IR) have
      been clinically reported to lead insulin resistance and insulin hypersecretion in
      humans. However, it has not been completely clarified how insulin resistance and
      pancreatic beta-cell function affect each other under the expression of mutant
      IR. We investigated the response of pancreatic beta-cells in mice carrying a
      mutation (P1195L) in the tyrosine kinase domain of IR beta-subunit. Homozygous
      (Ir(P1195L/P1195L)) mice showed severe ketoacidosis and died within 2 days after
      birth, and heterozygous (Ir(P1195L/wt)) mice showed normal levels of plasma
      glucose, but high levels of plasma insulin in the fasted state and after glucose
      loading, and a reduced response of plasma glucose lowering effect to exogenously
      administered insulin compared with wild type (Ir(wt/wt)) mice. There were no
      differences in the insulin receptor substrate (IRS)-2 expression and its
      phosphorylation levels in the liver between Ir(P1195L/wt) and Ir(wt/wt) mice,
      both before and after insulin injection. This result may indicate that IRS-2
      signaling is not changed in Ir(P1195L/wt) mice. The beta-cell mass increased due
      to the increased numbers of beta-cells in Ir(P1195L/wt) mice. More proliferative
      beta-cells were observed in Ir(P1195L/wt) mice, but the number of apoptotic beta
      cells was almost the same as that in Ir(wt/wt) mice, even after streptozotocin
      treatment. These data suggest that, in Ir(P1195L/wt) mice, normal levels of
      plasma glucose were maintained due to high levels of plasma insulin resulting
      from increased numbers of beta-cells, which in turn was due to increased beta
      cell proliferation rather than decreased beta-cell apoptosis.

PMID- 17003276
TI  - Gastric estrogen directly induces ghrelin expression and production in the rat
      stomach.
AB  - Ghrelin, an endogenous ligand for the GH secretagogue receptor, is predominantly
      produced in the stomach. Little is known about the regulation mechanism of
      gastric ghrelin. Here, we report that estrogen synthesized in the stomach induces
      rat gastric ghrelin gene expression and production. We established a gastric
      ghrelin cell enrichment method using Percoll centrifugation and then studied the
      effect of estrogen and/or its antagonist on ghrelin expression and production.
      Treatment with estrogen for 8 h significantly increased the level of ghrelin
      expression, and ICI-182 780, an estrogen receptor (ER) antagonist, completely
      reversed this effect. Reverse transcriptase-PCR analysis clearly showed that
      ERalpha and aromatase are expressed in the female rat stomach. Moreover,
      treatment with an aromatase inhibitor, 4-hydro-xyandrostenedione (formestane),
      significantly decreased the level of ghrelin mRNA expression in minced stomach
      tissue. In vivo studies revealed that the ghrelin mRNA expression and production
      did not change in gonadectomized rat 3 weeks after surgery. These results
      strongly suggest that estrogen produced in the stomach directly induces ghrelin
      expression and production in both female and male rat stomachs.

PMID- 17003277
TI  - A complex containing alpha6beta1-integrin and phosphorylated focal adhesion
      kinase between Sertoli cells and elongated spermatids during spermatid release
      from the seminiferous epithelium.
AB  - Spermiation is the final step of spermatogenesis and culminates in the
      disengagement (release) of elongated spermatids from Sertoli cells into the
      seminiferous tubule lumen. Spermiation failure, wherein spermatids are retained
      by Sertoli cells instead of releasing, occurs after hormone suppression. The
      mechanisms involved in spermatid disengagement and retention are not well
      understood. We previously showed that beta(1)-integrin is associated with
      spermatids until the point of disengagement, but the ectoplasmic specialisation
      junction (ES) is not. The aims of this paper are to further characterise the
      complex that is present immediately prior to spermatid disengagement by
      identifying the alpha-integrin form dimerised with beta(1)-integrin, localising
      focal adhesion kinase (FAK) and determining if microtubules are involved. Adult
      Sprague-Dawley rats received testosterone and oestradiol implants and an FSH
      antibody for 7 days to suppress testicular testosterone and FSH and induce
      spermiation failure. Control rats were treated with saline. Immunohistochemical
      analysis showed that alpha(6)-integrin and a phosphorylated form of FAK (FAK
      Tyr(397)) are present between late spermatids and Sertoli cells after ES removal,
      until the point of disengagement, and both proteins remain associated with
      retained spermatids after spermiation failure induced by hormone suppression.
      Using dual-label immunofluorescence, tubulins (and thus microtubules) were
      observed to co-localise with ES, but were neither associated with elongated
      spermatids just prior to release nor with retained spermatids following hormone
      suppression. These results suggest that microtubules are not involved in the
      final release of spermatids from Sertoli cells. We conclude that spermatid
      release during spermiation is mediated by a 'disengagement complex' containing
      alpha(6)beta(1)-integrin and phospho-FAK, the function of which can be affected
      by gonadotrophin suppression.

PMID- 17003278
TI  - Orchidectomy increases expression and activity of Cu/Zn-superoxide dismutase,
      while decreasing endothelial nitric oxide bioavailability.
AB  - This study examines the effect of male sex hormones on the release, metabolism
      and function of endothelial nitric oxide (eNO) in rat aorta. Aortic segments from
      orchidectomized and control male Sprague-Dawley rats were used to measure eNO
      synthase (eNOS) expression, nitric oxide (NO) release, acetylcholine (ACh)- and
      sodium nitroprusside (SNP)-induced relaxation and Cu/Zn-superoxide dismutase
      (SOD) expression and activity. eNOS expression as well as basal and ACh-induced
      NO release were similar in arteries from both groups of rats. Basal superoxide
      anion production was similar in arteries from both groups, while ACh-induced
      superoxide anion formation was greater in arteries from orchidectomized than
      control rats. Orchidectomy increased the vasodilator effect induced by ACh, but
      did not alter that induced by SNP. SOD, a superoxide anion scavenger, did not
      modify the SNP-induced relaxation in aortas from control or orchidectomized rats.
      The membrane-permeable mimetic of SOD, tempol, increased the SNP-induced
      relaxation more in aortas from orchidectomized than control rats. The effect of
      endogenous SOD inhibitor, diethyl-dithiocarbamate, reduced the relaxation induced
      by SNP in segments from both groups of rats. The expression and activity of Cu/Zn
      SOD were greater in aortas from orchidectomized than control rats. These data
      show that endogenous male sex hormone deprivation altered neither eNOS expression
      nor eNO release, while it increased the expression and activity of Cu/Zn-SOD.
      However, the predominant vascular effect of orchidectomy is to increase NO
      metabolism.

PMID- 17003279
TI  - Region-specific expression of androgen and growth factor pathway genes in the rat
      epididymis and the effects of dual 5alpha-reductase inhibition.
AB  - Dihydrotestosterone (DHT) is the primary androgen acting in the epididymis, the
      site of sperm maturation. Previously, we showed that the treatment of male rats
      with PNU157706, an inhibitor that acts on both isoforms of 5alpha-reductase to
      prevent DHT formation, has effects on the expression of genes implicated in
      processes that create the optimal luminal microenvironment required for sperm
      maturation, and on sperm maturation itself. However, signaling pathways involved
      in regulating or mediating DHT actions in the epididymis remain largely unknown.
      The goals of this study were to determine the expression profiles of potential
      signaling systems in the epididymis and assess their DHT-dependence using two
      different dual 5alpha-reductase inhibitors. Rats were untreated or gavaged with
      vehicle, 10 mg/kg per day PNU157706 or 32 mg/kg per day FK143 for 28 days and
      epididymal gene expression was analyzed. Gene array analysis revealed analogous
      effects of FK143 on overall epididymal gene expression when compared with
      previous PNU157706 studies. Quantitative RT-PCR analysis of the expression of the
      5alpha-reductase isozymes, androgen receptor, and members of the IGF, FGF, TGF,
      and VEGF families revealed novel region-specific expression profiles in the
      epididymis that were differentially affected by 5alpha-reductase inhibition; the
      two inhibitors had parallel effects. Specifically, in proximal regions, 5alpha
      reductase 1, androgen receptor, and TGF-beta1 expression increased after
      treatment, while in distal regions expression of IGF-I, IGFBP-5, IGFBP-6, and FGF
      10 decreased. These results provide insight into epididymal signaling mechanisms
      and indicate potential candidates acting either upstream or downstream of DHT to
      regulate and/or mediate its actions in the epididymis.

PMID- 17003280
TI  - Identification of prostatic-secreted proteins in mice by mass spectrometric
      analysis and evaluation of lobe-specific and androgen-dependent mRNA expression.
AB  - Rats and guinea pigs have frequently been used to study the development of the
      prostate and the mechanism of androgen action, but the mouse prostate has also
      become an attractive model for prostate research, because an enormous range of
      genetically altered mice is now available. However, the secretion of proteins in
      the mouse prostate has not yet been thoroughly investigated. In the present
      study, major secreted proteins from the ventral prostate (VP), dorso-lateral
      prostate (DLP), and anterior prostate (AP) of mice were identified by means of 2D
      gel electrophoresis followed by MALDI-TOF mass spectrometric analysis. A
      quantitative reverse transcriptase-PCR method was further employed to examine the
      androgen-dependent transcriptional regulation of the identified proteins.
      Proteome analysis revealed that the VP secretes spermine-binding protein, serine
      protease inhibitor Kazal type-3, and a 91 kDa hypothetical scavenger receptor
      (AK035662). DLP and AP secrete a protein similar to immunoglobulin-binding
      protein, immunoglobulin-binding protein-like protein, and one of the experimental
      autoimmune prostatitis antigen proteins (EAPA2). Peroxiredoxin-6, glucose
      regulated protein 78, zinc-alpha2-glycoprotein, and phospholipase Calpha are also
      secreted. Castration of animals led to a decrease in the mRNAs of these secreted
      proteins, although the extents of changes varied greatlyamong different lobes. We
      present here an outlined view of mouse prostate secretion, which should
      contribute to an understanding of the biological functions of the prostate gland,
      as well as the androgen dependency of prostate secretion.

PMID- 17003281
TI  - Enhanced formation of non-phenolic androgen metabolites with intrinsic oestrogen
      like gene transactivation potency in human breast cancer cells: a distinctive
      metabolic pattern.
AB  - Breast cancer is a sex steroid hormone-dependent malignant neoplasia. The role of
      oestradiol in this malignancy has been well documented; however, the involvement
      of androgens has remained controversial. To determine the role of non-phenolic
      androgen metabolites in human breast cancer, we studied the metabolism of [(14)C]
      testosterone and [(14)C] androstenedione in oestrogen-dependent MCF-7 cells and
      non-oestrogen-dependent MDA-MB 231 cells, at different substrate concentrations
      (1-10 muM) and time periods (30 min-48 h). Cultured non-oestrogen-dependent HeLa
      and yeast cells served as controls. Metabolites were identified and quantified by
      reverse isotope dilution. A distinctive pattern of androgen metabolism was
      identified in MCF-7 cells, being the 5alpha-androstane-3alpha,17beta-diol
      (3alpha,5alpha-diol) and its 3beta epimer (3beta,5alpha-diol), the major
      conversion products of testosterone (48.3%), with 5alpha-dihydrotestosterone as
      intermediary. The formation of 3alpha,5alpha-diol and 3beta,5alpha-diol (diols)
      was substrate concentration- and time-dependent, and abolished by finasteride. In
      contrast, very little of any diol formation was observed in MDA-MB 231, HeLa and
      yeast cell incubations. Additional enzyme gene expression studies revealed an
      overexpression of 5alpha-steroid reductase type-1 in MCF-7 cells, as compared
      with MDA-MB 231 cells. The oestrogen-like activities of diols were assessed in
      HeLa cells co-transfected with expression vectors for alpha or beta subtypes of
      the human oestrogen receptor (hER) genes and for an oestrogen-responsive reporter
      gene. The results show that 3beta, 5alpha-diol and to a lesser extent
      3alpha,5alpha-diol bind with high relative affinity to hERalpha and hERbeta. Both
      diols induced hER-mediated reporter gene transactivation in a dose-response
      manner, similar to that induced by oestradiol, though with lower potency, an
      effect that was abolished by ICI-182 780. Furthermore, 3beta,5alpha-diol and to
      lesser extent 3alpha,5alpha-diol induced MCF-7 cell proliferation. The overall
      results demonstrated that MCF-7 cells exhibit enhanced expression and activity of
      androgen-metabolising enzymes, leading to rapid and large diol formation, and
      provide evidence that these androgen metabolites exert a potent oestrogen
      agonistic effect, at genomic level, in oestrogen-dependent breast cancer cells.
      The data suggest that diols may act as in situ intracrine factors in breast
      cancer and that its formation can be pharmacologically inhibited.

PMID- 17003282
TI  - Estrogen-dependent responses of the mammary fat pad in prepubertal dairy heifers.
AB  - Ovaries are absolutely required for development of the mammary parenchyma (PAR)
      in cattle, reflecting estrogen-dependent epithelial cell proliferation. However,
      the estrogen receptor (ER) that mediates the mammary estrogen effects, ERalpha,
      is absent in proliferating epithelial cells. In the mouse, this discrepancy is
      explained in part by the ability of the mammary fat pad (MFP) to synthesize
      epithelial cell mitogens such as IGF-I in response to estrogen. Consistent with a
      similar role for the bovine MFP, 30% of its fibroblasts and adipocytes were
      immunoreactive for ERalpha in prepubertal dairy heifers. To assess estrogen
      dependent gene expression in the MFP, 16 prepubertal dairy heifers were randomly
      assigned to a 2x2 factorial. The first factor was ovarian status, with heifers
      undergoing bilateral ovariectomy or left intact at 4.6 months of age. The second
      factor was applied 30 days after surgery and consisted of injection of estrogen
      or excipient. After 3 days of injection, heifers were administered an
      intrajugular bolus of bromodeoxyuridine (BrdU) and slaughtered 2 h later. The
      estrogen injection, but not ovarian status, caused significant increases in the
      fraction of epithelial cells labeled with BrdU and produced tissue-specific
      effects on gene expression. In the PAR, estrogen injection increased IGF-I gene
      expression by twofold despite reductions of 50% or more in ERalpha mRNA abundance
      and the fraction of epithelial cells immunoreactive for ERalpha. The estrogen
      dependent increase in IGF-I mRNA was greater in the MFP, presumably because
      estrogen failed to downregulate ERalpha expression in this mammary compartment.
      Finally, estrogen-responsiveness of the MFP appears unique among the bovine fat
      depots as estrogen injection did not induce IGF-I expression in its s.c.
      counterpart. Our data demonstrate that the bovine MFP is highly responsive to
      exogenous estrogen, consistent with a role for this tissue compartment in
      communicating its effects on epithelial cell proliferation.

PMID- 17003283
TI  - Cyclic changes in the vaginal epithelium of normal rhesus macaques.
AB  - Studies in nonhuman primates indicate that changes in the thickness and integrity
      of the vaginal epithelium affect the transmission rates of HIV-1, but few studies
      have examined the normal variations that may occur in the vagina of normal
      macaques as a result of aging or changes in the menstrual cycle. This study was
      conducted to determine if differences occur in the thickness of the vaginal
      mucosa with age or menses. Vaginal mucosal thickness was compared in 46 rhesus
      macaques grouped as juvenile (1-3 years old), mature cycling (3-21 years old),
      and geriatric (> 21 years old). Epithelia of mature cycling macaques were also
      compared at different stages of the menstrual cycle. Older females (> 21 years)
      had the thinnest and least keratinized epithelium of all groups, followed by the
      youngest females (< 3 years). The vaginal epithelium was also thinner in cycling
      macaques during menses compared to the follicular stage. In addition, young,
      geriatric, or cycling macaques during menses had minimal keratinization. We
      hypothesize that normal physiologic changes in the vaginal epithelium of women
      occur with age and menses, which may affect a woman's susceptibility to HIV-1
      transmission and other sexually transmitted diseases. Also, age and menstrual
      cycle should be considered when designing vaginal transmission experiments in
      rhesus macaques.

PMID- 17003284
TI  - Differential expression and regulation of progesterone receptor isoforms in rat
      and mouse pituitary cells and LbetaT2 gonadotropes.
AB  - Manipulation of endogenous progesterone receptor (PR) does not produce equivalent
      physiological effects in mouse and rat pituitary cells. To test whether this may
      be due in part to difference in PR isoform expression, we examined hormonally
      regulated pituitary PR-A and PR-B mRNA levels using quantitative real-time PCR.
      The LbetaT2 mouse gonadotrope line or pituitary cells from adult, ovariectomized
      rats or mice were cultured with or without 0.2 nM 17beta-estradiol (E(2)) for 3
      days. PR-A was the predominant form expressed for all groups. For mouse cells,
      E(2) led to an increase in both isoforms without a change in the A:B ratio; for
      rat cells, the PR-B response to E(2) was more robust resulting in a decrease in
      the A:B ratio. Exposure of E(2)-treated pituitary cells to 200 nM progesterone
      for 6 h decreased both PR-A and PR-B levels in rat cells, but had no effect on PR
      isoform expression in mouse cells even when exposure was extended to 12 h. The
      low level of PR expression found in LbetaT2 gonadotropes was unaffected by E(2),
      alone or with progesterone. The weak PR expression and lack of responsiveness of
      LbetaT2 cells cannot be explained by a male phenotype as was shown by the more
      than tenfold higher PR mRNA level in primary cultures of male mouse pituitary
      cells, which responded to E(2) stimulation with a proportional increase in PR
      isoforms similar to female cells. Functionally, E(2)-stimulated changes in PR
      mRNA isoform ratios in rat, mouse or LbetaT2 cells correlated with the degree of
      progesterone augmentation of GnRH-stimulated LH secretion in these models. These
      results are consistent with the hypothesis that robust GnRH priming and
      progesterone augmentation of LH secretion in the rat compared to these events in
      the mouse are a consequence, in part, of differences in the E(2)-modulated ratio
      of PR isoforms.

PMID- 17003285
TI  - Nitric oxide production by hepatocytes contributes to the inhibitory effect of
      endotoxin on insulin-like growth factor I gene expression.
AB  - We tested whether endotoxin (lipopolysaccharide, LPS) inhibits IGF-I gene
      expression in hepatocytes and the possible role of Kupffer cells and nitric oxide
      (NO) in this effect. LPS decreased IGF-I mRNA in hepatocyte cultures and
      increased the nitrite + nitrate levels in the culture medium. Furthermore, there
      was a negative correlation between the IGF-I mRNA and the nitrite+nitrate levels.
      When hepatocytes were cocultured with Kupffer cells, the inhibitory effect of LPS
      on IGF-I mRNA was higher than in hepatocyte cultures, but the stimulatory effect
      on nitrite+nitrate was similar in both conditions. The exogenous NO donated by S
      nitroso-n-acetyl-d,l-penicillamide also decreased the IGF-I gene expression in
      hepatocyte cultures. In addition, two specific inducible NO synthase (iNOS)
      inhibitors, l-N6-(1-iminoethyl)lysine (l-NIL) and aminoguanidine, prevented the
      effect of LPS on nitrite+nitrate levels and on IGF-I gene expression in
      hepatocyte cultures. These data indicate that iNOS-derived NO may cause
      downregulation of IGF-I gene expression in hepatocytes. However, in cocultures,
      the iNOS inhibitor l-NIL prevented the effect of LPS on nitrite+nitrate levels,
      but only attenuated the LPS-induced decrease in IGF-I gene expression. We
      conclude that in hepatocytes, LPS-induced decrease in IGF-I is mainly due to
      induction of iNOS, whereas in the presence of Kupffer cells LPS inhibits IGF-I
      through NO release and through other inhibitory pathways.

PMID- 17003286
TI  - Developmental and hormonal regulation of progesterone receptor A-form expression
      in female mouse lung in vivo: interaction with glucocorticoid receptors.
AB  - Progesterone (P(4)) regulates many aspects of physiological functions via two
      nuclear P(4) receptors (PR), PRA and PRB, which are members of a structurally
      related nuclear hormone receptor superfamily that includes glucocorticoid
      receptors (GR). The regulation and cellular distribution of PR protein isoforms
      have been extensively studied in reproductive tissues, but this is not the case
      in the lung. In the present study, reverse transcriptase (RT)-PCR, Western
      blotting, and immunolocalization supported the presence of PRA in the lung of
      female mice, with PRA protein levels significantly increased between postnatal
      day 7 and 12, declined at postnatal day 26, and minimal in adults when compared
      to postnatal day 2. The peak was temporally related to postnatal lung maturation
      in rodents. Immunoreactivity for PR was detected in the alveolar and bronchial
      epithelia. We then extended this study to examine, for the first time, the
      regulation of PRA protein expression in female mouse lung in vivo. Neither the
      increase in endogenous P(4) nor treatment with exogenous P(4) regulated PRA
      protein expression in female mouse lung. However, treatment of mice with the
      GR/PR antagonist RU 486, but not Org 31710 (a specific PR antagonist),
      significantly increased PRA protein expression in parallel to a decrease in GR
      protein expression. In addition, treatment with the synthetic glucocorticoid
      dexamethasone led to a decrease in PRA protein expression independent of
      endogenous P(4) levels. Furthermore, immunoprecipitation followed by Western blot
      analysis revealed that, under in vivo conditions, PRA physically interacted with
      GR in mouse lung. Confocal laser microscopy revealed that PRA and GR co-localized
      in the nuclei of alveolar epithelia cells, whereas nuclear PR and cytoplasmic GR
      were detected in bronchial epithelium. Taken together, our observations suggest
      that PRA may be an important physiological factor involved in postnatal lung
      development and that the regulation of PRA protein expression is not dependent on
      P(4), but rather on functional glucocorticoid/GR signaling mediated by protein
      protein interaction in the mouse lung.

PMID- 17003287
TI  - The involvement of epoxygenase metabolites of arachidonic acid in cAMP-stimulated
      steroidogenesis and steroidogenic acute regulatory protein gene expression.
AB  - The essential role of arachidonic acid (AA) in steroidogenesis has been
      previously demonstrated. The present study continues the investigation into how
      AA regulates steroidogenesis by examining the effects of epoxygenase-derived AA
      metabolites on cAMP-stimulated steroidogenic acute regulatory (StAR) gene
      expression and steroid hormone production in MA-10 mouse Leydig cells. The HPLC
      analysis of cell extracts from MA-10 cells treated with the cAMP analog dibutyryl
      cAMP (dbcAMP) demonstrated an increase in three epoxygenase-generated AA
      metabolites: 5,6-epoxyeicosatrienoic acid (EET), 8,9-EET, and 11,12-EET.
      Incubating MA-10 cells with each of the EETs induced a dose-dependent increase in
      StAR protein expression and steroid hormone production in the presence of dbcAMP.
      These metabolites also significantly enhanced StAR gene transcription as
      determined by luciferase assays of StAR promoter activity and reverse
      transcriptase-PCR analysis of StAR mRNA levels. While the EETs enhanced
      steroidogenesis, inhibiting the activity of protein kinase A (PKA) abolished the
      stimulatory effects of these AA metabolites on StAR expression and steroid
      hormone production. This study suggests that cAMP stimulation of MA-10 cells
      increases epoxygenase-generated AA metabolites and the co-action of these
      metabolites with PKA significantly increases StAR gene expression and steroid
      hormone production.

PMID- 17003288
TI  - Identification, characterization, and quantitative expression analysis of rainbow
      trout myostatin-1a and myostatin-1b genes.
AB  - Myostatin is a potent negative regulator of skeletal muscle growth. Although
      several cDNA clones have been characterized in different vertebrates, the genomic
      organization and bioactivity of non-mammalian homologs have not. The intron/exon
      organization and promoter subsequence analysis of two rainbow trout myostatin
      genes, rtMSTN-1a and rtMSTN-1b (formerly 1 and 2 respectively), as well as a
      quantitative assessment of their embryonic, larval, and adult tissue expression
      profiles are reported herein. Each gene was similarly organized into three exons
      of 490, 368, and 1600 bp for MSTN-1a and 486, 386, and 1419 bp for MSTN-1b.
      Comparative mapping of coding regions from several vertebrate myostatin genes
      revealed a common organization between species, including conserved pre-mRNA
      splice sites; the first among the fishes and the second across all vertebrate
      species. In silico subsequence analysis of the promoter regions identified E
      boxes and other putative myogenic response elements. However, the number and
      diversity of elements were considerably less than those found in mammalian
      promoters or in the recently characterized zebrafish MSTN-2 gene. A quantitative
      analysis of the embryonic expression profile for both genes indicates that rtMSTN
      1a expression is consistently greater than that of rtMSTN-1b and neither gene is
      significantly expressed throughout gastrulation. Expression of both steadily
      increases fourfold during somitogenesis and subsides as this period ends. After
      eyeing, however, rtMSTN-1a mRNA levels ultimately rise 20-fold by day 49 and peak
      before hatching and yolk sac absorption (YSA). Levels of rtMSTN-1b rise
      similarly, but do not peak before YSA. An analysis of adult (2-year-old fish)
      tissue expression indicates that both transcripts are present in most tissues
      although levels are highest in brain, testes, eyes, muscle, and surprisingly
      spleen. These studies suggest that strong selective pressures have preserved the
      genomic organization of myostatin genes throughout evolution. However, the
      different expression profiles and putative promoter elements in fishes versus
      mammals suggests that limitations in myostatin function may have evolved
      recently.

PMID- 17003289
TI  - Actions of glucagon-like peptide-1 on KATP channel-dependent and -independent
      effects of glucose, sulphonylureas and nateglinide.
AB  - This study examined the effects of glucagon-like peptide-1 (GLP-1) on insulin
      secretion alone and in combination with sulphonylureas or nateglinide, with
      particular attention to K(ATP) channel-independent insulin secretion. In
      depolarised cells, GLP-1 significantly augmented glucose-induced K(ATP) channel
      independent insulin secretion in a glucose concentration-dependent manner. GLP-1
      similarly augmented the K(ATP) channel-independent insulin-releasing effects of
      tolbutamide, glibenclamide or nateglinide. Downregulation of protein kinase A
      (PKA)- or protein kinase C (PKC)-signalling pathways in culture revealed that the
      K(ATP) channel-independent effects of sulphonylureas or nateglinide were
      critically dependent upon intact PKA and PKC signalling. In contrast, GLP-1
      exhibited a reduced but still significant insulin-releasing effect following PKA
      and PKC downregulation, indicating that GLP-1 can modulate K(ATP) channel
      independent insulin secretion by protein kinase-dependent and -independent
      mechanisms. The synergistic insulin-releasing effects of combinatorial GLP-1 and
      sulphonylurea/nateglinide were lost following PKA- or PKC-desensitisation,
      despite GLP-1 retaining an insulin-releasing effect, demonstrating that GLP-1 can
      induce insulin release under conditions where sulphonylureas and nateglinide are
      no longer effective. Our results provide new insights into the mechanisms of
      action of GLP-1, and further highlight the promise of GLP-1 or similarly acting
      analogues alone or in combination with sulphonylureas or meglitinide drugs in
      type 2 diabetes therapy.

PMID- 17003290
TI  - The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene
      expression in human colon cancer LS174T cells.
AB  - Resistance to anticancer drugs is often mediated by the overexpression of P
      glycoprotein encoded by the multi-drug resistance (MDR1) gene. The nuclear
      receptor, steroid and xenobiotic receptor (SXR), is one of the key
      transcriptional regulators of MDR1 gene expression. A variety of xenobiotics bind
      to SXR, and stimulate transcription on xenobiotic-response elements (XREs),
      located in the MDR1 gene promoter. Diethylhexyl phthalate (DEHP) is widely used
      as a plasticizer for polyvinyl chloride (PVC) medical devices. Previous studies
      have shown that a significant amount of DEHP leaches from PVC infusion bags and
      lines during interventions, such as total parenteral nutrition, blood
      transfusion, and cancer chemotherapy. Thus, the leaching of DEHP during
      parenteral chemotherapy for cancer patients may facilitate MDR1 expression in
      various tissues, including cancer cells, which may promote drug resistance. To
      examine such a hypothesis, the effect of DEHP on SXR-mediated transcription of
      the MDR1 gene was studied in the human colon adenocarcinoma-derived cell line,
      LS174T cells, which endogenously express SXR. DEHP increased the SXR-mediated
      transcription of the MDR1 gene in luciferase-reporter assays. The induction by
      DEHP was abrogated when a reporter plasmid containing mutated DR+4 motif in the
      XRE was used. In a mammalian two-hybrid assay, DEHP recruited steroid receptor co
      activator-1 to the ligand-binding domain of SXR. Finally, using real-time reverse
      transcriptase-PCR, we showed that DEHP increased MDR1 gene expression in a dose
      dependent manner. We conclude that DEHP is an inducer of the MDR1 gene in this
      cell line. As such, the leaching of DEHP from the PVC medical devices may
      influence the MDR1 expression, which may induce resistance to drugs in certain
      populations of cancer cells.

PMID- 17003291
TI  - A double-blind, placebo-controlled trial assessing pramlintide treatment in the
      setting of intensive insulin therapy in type 1 diabetes.
AB  - OBJECTIVE: To assess safety, efficacy, and tolerability of pramlintide dose
      escalation with proactive mealtime insulin reduction, followed by insulin
      optimization, in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: This
      29-week, double-blind, placebo-controlled study randomized 296 patients to
      pramlintide or placebo as an adjunct to insulin. During initiation, pramlintide
      was escalated from 15 to 60 microg/meal (15-microg increments) with recommended
      reductions (30-50%) in mealtime insulin. Insulin was subsequently adjusted to
      optimize glycemic control. End points included safety and change in HbA1c (A1C),
      postprandial glucose, insulin, weight, and tolerability. RESULTS: Baseline A1C
      was 8.1% for both groups and at week 29 had decreased comparably (pramlintide 
      0.5% [95% CI -0.61 to -0.33]; placebo -0.5% [-0.63 to -0.35]). Pramlintide
      treatment significantly reduced postprandial glucose excursions (incremental area
      under the curve [AUC](0-3h): pramlintide -175 +/- 40, placebo -64 +/- 38 mg x h(
      1) x dl(-1); P < 0.0005) and weight (pramlintide -1.3 +/- 0.30, placebo +1.2 +/-
      0.30 kg; P < 0.0001). At week 29, insulin dose decreased by 28 and 4% in
      pramlintide- and placebo-treated groups, respectively. Nausea, reported by 63 and
      36% of patients in pramlintide and placebo groups (P < 0.01), respectively, was
      predominately mild to moderate in intensity. Severe hypoglycemia rates were low
      in both groups (pramlintide 0.57 +/- 0.09, placebo 0.30 +/- 0.06 event
      rate/patient-year; P < 0.05), with increased rates observed in patients remaining
      at 30 microg pramlintide. CONCLUSIONS: Pramlintide dose escalation with reduced
      mealtime insulin was effective during therapy initiation in patients with type 1
      diabetes. While both groups experienced equivalent A1C reductions relative to
      placebo, pramlintide-treated patients experienced reductions in postprandial
      glucose excursions and weight, not achievable with insulin therapy alone.

PMID- 17003292
TI  - Flexible intensive insulin therapy in adults with type 1 diabetes and high risk
      for severe hypoglycemia and diabetic ketoacidosis.
AB  - OBJECTIVE: Diabetes treatment and teaching programs (DTTPs) for type 1 diabetes,
      which teach flexible intensive insulin therapy to enable dietary freedom, have
      proven to be safe and effective in routine care. This study evaluates DTTP
      outcomes in patients at high risk for severe hypoglycemia and severe
      ketoacidosis. RESEARCH DESIGN AND METHODS: There were 96 diabetes centers that
      participated between 1992 and 2004. A total of 9,583 routine-care patients with
      type 1 diabetes were examined before and 1 year after a DTTP. History of repeated
      severe hypoglycemia/severe ketoacidosis was an indication for DTTP participation.
      Before-after analyses were performed for subgroups of patients with three or more
      episodes of severe hypoglycemia or two or more episodes of severe ketoacidosis
      during the year before a DTTP. Main outcome measures were GHb, severe
      hypoglycemia, severe ketoacidosis, and hospitalization. RESULTS: A total of 341
      participants had three or more episodes of severe hypoglycemia the year before a
      DTTP. Mean baseline GHb was 7.4 vs. 7.2% after the DTTP, incidence of severe
      hypoglycemia was 6.1 vs. 1.4 events x patient(-1) x year(-1), and hospitalization
      was 8.6 vs. 3.9 days x patient(-1) x year(-1). In mixed-effects models taking
      effects of centers and diabetes duration into account, mean difference was -0.3%
      (95% CI -0.5 to -0.1%; P = 0.0006) for GHb and -4.7 events x patient(-1) x year(
      1) (-5.4 to -4; P < 0.0001) for severe hypoglycemia. A total of 95 patients had
      two or more episodes of severe ketoacidosis. GHb was 9.4% at baseline versus 8.7%
      after DTTP; incidence of severe ketoacidosis was 3.3 vs. 0.6 events x patient(-1)
      x year(-1), and hospitalization was 19.4 vs. 10.2 days x patient(-1) x year(-1).
      In linear models with diabetes duration as the fixed effect, the adjusted mean
      difference was -2.7 events x patient(-1) x year(-1) (95% CI -3.3 to -2.1; P <
      0.0001) for severe ketoacidosis and -8.1 days (-12.9 to -3.2; P = 0.0014) for
      hospitalization. CONCLUSIONS: Patients at high risk for severe hypoglycemia or
      severe ketoacidosis may benefit from participation in a standard DTTP for
      intensive insulin therapy and dietary freedom.

PMID- 17003293
TI  - Prevention of hypoglycemia during exercise in children with type 1 diabetes by
      suspending basal insulin.
AB  - OBJECTIVE: Strategies for preventing hypoglycemia during exercise in children
      with type 1 diabetes have not been well studied. The Diabetes Research in
      Children Network (DirecNet) Study Group conducted a study to determine whether
      stopping basal insulin could reduce the frequency of hypoglycemia occurring
      during exercise. RESEARCH DESIGN AND METHODS: Using a randomized crossover
      design, 49 children 8-17 years of age with type 1 diabetes on insulin pump
      therapy were studied during structured exercise sessions on 2 days. On day 1,
      basal insulin was stopped during exercise, and on day 2 it was continued. Each
      exercise session, performed from approximately 4:00-5:00 p.m., consisted of four
      15-min treadmill cycles at a target heart rate of 140 bpm (interspersed with
      three 5-min rest breaks over 75 min), followed by a 45-min observation period.
      Frequently sampled glucose concentrations (measured in the DirecNet Central
      Laboratory) were measured before, during, and after the exercise. RESULTS:
      Hypoglycemia (< or = 70 mg/dl) during exercise occurred less frequently when the
      basal insulin was discontinued than when it was continued (16 vs. 43%; P =
      0.003). Hyperglycemia (increase from baseline of > or = 20% to > or = 200 mg/dl)
      45 min after the completion of exercise was more frequent without basal insulin
      (27 vs. 4%; P = 0.002). There were no cases of abnormal blood ketone levels.
      CONCLUSIONS: Discontinuing basal insulin during exercise is an effective strategy
      for reducing hypoglycemia in children with type 1 diabetes, but the risk of
      hyperglycemia is increased.

PMID- 17003294
TI  - The sensitivity and specificity of nonmydriatic digital stereoscopic retinal
      imaging in detecting diabetic retinopathy.
AB  - OBJECTIVE: The objective of this study was to determine the sensitivity and
      specificity of Joslin Vision Network nonmydriatic digital stereoscopic retinal
      imaging (NMDSRI) as a screening tool in detecting diabetic retinopathy. RESEARCH
      DESIGN AND METHODS: We reviewed the records of 244 patients with diabetes who had
      a dilated funduscopic examination (DFE) and NMDSRI done within 1 year of each
      other at four locations in the metropolitan Washington, DC, area. The images were
      transmitted through a local area network to a central reading location where they
      were graded by a single retinal specialist. RESULTS: Images of 482 eyes from 243
      patients were included in the study. Four images did not transmit, and 35% of the
      images were not gradable. Of the remaining 311 eyes, there was 86% agreement in
      the grading between NMDSRI and DFE: 227 eyes with no diabetic retinopathy and 40
      eyes with diabetic retinopathy. In 46 eyes (15%) there was a disagreement between
      gradings made by the two techniques. NMDSRI detected diabetic retinopathy in 35
      eyes reported as normal by DFE, and in the remaining 11 eyes, the DFE grade was
      one grade higher than the NMDSRI grade. Adjudicated nonconcordant examinations
      were within one grade. In the 76 eyes with diabetic retinopathy, retinal
      thickness could not be assessed in 17 (21%) eyes. When the NMDSRI result was
      gradable, the overall sensitivity of NMDSRI was 98% and the specificity was 100%
      for retinopathy within one grade of the DFE. In the limited number of eyes that
      had diabetic retinopathy with macular edema (six), agreement with the clinical
      examination was 100%. CONCLUSIONS: NMDSRI is a sensitive and specific method for
      the screening and diagnosis of diabetic retinopathy, which may help improve
      compliance with the standards of eye care for patients with diabetes.

PMID- 17003295
TI  - Efficacy and safety of angiotensin II receptor blockade in elderly patients with
      diabetes.
AB  - OBJECTIVE: While national guidelines recommend ACE inhibitor (ACEI) or
      angiotensin receptor blocker (ARB) therapy in patients with diabetes and
      nephropathy, guidelines concerning elderly patients with diabetes have not
      endorsed these drugs. We sought to assess the nephroprotective efficacy and
      safety of ARB therapy in elderly patients by conducting age-specific subgroup
      analyses using data from the Reduction of Endpoints in NIDDM with the Angiotensin
      II Antagonist Losartan (RENAAL) study. RESEARCH DESIGN AND METHODS: We studied
      1,513 patients with type 2 diabetes and nephropathy who randomly received either
      losartan or placebo. We tested for effect modification by age of the effect of
      losartan on the incidence of the predefined end points (doubling of serum
      creatinine, end-stage renal disease [ESRD], or death) and the risk of adverse
      events. RESULTS: Of 1,513 participants, 421 (27.8%) were aged >65 years (maximum
      age 74 years). Age did not modify the efficacy of losartan in reducing the risk
      of the primary outcome, a composite of doubling of serum creatinine, ESRD, or
      death (P(interaction) = 0.66) or its individual components (all P(interaction) >
      0.44). In patients aged >65 years, losartan reduced the risk of ESRD by 50% (95%
      CI 30-81, P = 0.005). We found no evidence that older patients were more likely
      to experience adverse events from losartan such as a rise in serum creatinine or
      hyperkalemia than younger patients. CONCLUSIONS: Elderly patients had the same
      level of benefits and risks as younger patients from treatment with losartan.
      Underuse of ACEI and ARB therapy in elderly patients because of the perceived
      lack of efficacy or a greater risk of adverse events appears unjustified.

PMID- 17003296
TI  - Effect of weight loss and nutritional intervention on arterial stiffness in type
      2 diabetes.
AB  - OBJECTIVE: There is increased stiffness of the large central arteries in type 2
      diabetic patients, and obesity is a risk factor. However, the effect of
      intentional weight loss on arterial stiffness is uncertain, and the purpose of
      the current study was to assess this effect. RESEARCH DESIGN AND METHODS:
      Arterial stiffness was assessed by measuring aortic pulse wave velocity (aPWV) at
      baseline and at completion of a 1-year weight loss intervention. Metabolic
      control of type 2 diabetes was also appraised. RESULTS: Mean weight loss at 1
      year in 38 volunteers with type 2 diabetes was 7.8%. There were improvements in
      HbA1c, LDL cholesterol, homeostasis model assessment of insulin resistance, and
      inflammatory markers (plasminogen activator inhibitor-1, tumor necrosis factor
      alpha, interleukin-6, and C-reactive protein). There was also a significant
      improvement in aPWV at completion of weight loss intervention, from 740 to 690
      cm/s (P < 0.05). CONCLUSIONS: Moderate weight loss improves arterial stiffness in
      type 2 diabetes.

PMID- 17003297
TI  - Dietary fiber intake, dietary glycemic load, and the risk for gestational
      diabetes mellitus.
AB  - OBJECTIVE: We aimed to examine whether pregravid dietary fiber consumptions from
      cereal, fruit, and vegetable sources and dietary glycemic load were related to
      gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS: This study
      was a prospective cohort study among 13,110 eligible women in the Nurses' Health
      Study II. GDM was self-reported and validated by medical record review in a
      subsample. RESULTS: We documented 758 incident GDM cases during 8 years of follow
      up. After adjustment for age, parity, prepregnancy BMI, and other covariates,
      dietary total fiber and cereal and fruit fiber were strongly associated with GDM
      risk. Each 10-g/day increment in total fiber intake was associated with 26% (95%
      CI 9-49) reduction in risk; each 5-g/day increment in cereal or fruit fiber was
      associated with a 23% (9-36) or 26% (5-42) reduction, respectively. Dietary
      glycemic load was positively related to GDM risk. Multivariate relative risk for
      highest versus lowest quintiles was 1.61 (1.02-2.53) (P for trend 0.03). The
      combination of high-glycemic load and low-cereal fiber diet was associated with
      2.15-fold (1.04-4.29) increased risk compared with the reciprocal diet.
      CONCLUSIONS: These findings suggested that prepregnancy diet might be associated
      with women's GDM risk. In particular, diet with low fiber and high glycemic load
      was associated with an increased risk. Future clinical and metabolic studies are
      warranted to confirm these findings.

PMID- 17003298
TI  - Breast-feeding and risk for childhood obesity: does maternal diabetes or obesity
      status matter?
AB  - OBJECTIVE: We sought to evaluate whether maternal diabetes or weight status
      attenuates a previously reported beneficial effect of breast-feeding on childhood
      obesity. RESEARCH DESIGN AND METHODS: Growing Up Today Study (GUTS) participants
      were offspring of women who participated in the Nurses' Health Study II. In the
      present study, 15,253 girls and boys (aged 9-14 years in 1996) were included.
      Maternal diabetes and weight status and infant feeding were obtained by maternal
      self-report. We defined maternal overweight as BMI > or = 25 kg/m2. Childhood
      obesity, from self-reported height and weight, was based on the Centers for
      Disease Control and Prevention definitions as normal, at risk for overweight, or
      overweight. Maternal status categories were nondiabetes/normal weight,
      nondiabetes/overweight, or diabetes. Logistic regression models used generalized
      estimating equations to account for nonindependence between siblings. RESULTS:
      For all subjects combined, breast-feeding was associated with reduced overweight
      (compared with normal weight) in childhood. Compared with exclusive use of
      formula, the odds ratio (OR) for exclusive breast-feeding was 0.66 (95% CI 0.53
      0.82), adjusted for age, sex, and Tanner stage. Results did not differ according
      to maternal status (nondiabetes/normal weight OR 0.73 [95% CI 0.49-1.09];
      nondiabetes/overweight 0.75 [0.57-0.99]; and diabetes 0.62 [0.24-1.60]). Further
      adjustment for potential confounders attenuated results, but results remained
      consistent across strata of maternal status (P value for interaction was 0.50).
      CONCLUSIONS: Breast-feeding was inversely associated with childhood obesity
      regardless of maternal diabetes status or weight status. These data provide
      support for all mothers to breast-feed their infants to reduce the risk for
      childhood overweight.

PMID- 17003299
TI  - Dietary calcium and magnesium, major food sources, and risk of type 2 diabetes in
      U.S. black women.
AB  - OBJECTIVE: Inverse associations between magnesium and calcium intakes and risk of
      type 2 diabetes have been reported for studies in predominantly white
      populations. We examined magnesium, calcium, and major food sources in relation
      to type 2 diabetes in African-American women. RESEARCH DESIGN AND METHODS: This
      is a prospective cohort study including 41,186 participants of the Black Women's
      Health Study without a history of diabetes who completed validated food frequency
      questionnaires at baseline. During 8 years of follow-up (1995-2003), we
      documented 1,964 newly diagnosed cases of type 2 diabetes. RESULTS: The
      multivariate-adjusted hazard ratio of type 2 diabetes for the highest compared
      with the lowest quintile of intake was 0.69 (95% CI 0.59-0.81; P trend <0.0001)
      for dietary magnesium and 0.86 (0.74-1.00; P trend = 0.01) for dietary calcium.
      After mutual adjustment, the association for calcium disappeared (hazard ratio
      1.04 [95% CI 0.88-1.24]; P trend = 0.88), whereas the association for magnesium
      remained. Daily consumption of low-fat dairy (0.87 [0.76-1.00]; P trend = 0.04)
      and whole grains (0.69 [0.60-0.79]; P trend <0.0001) were associated with a lower
      risk of type 2 diabetes compared with a consumption less than once a week. After
      mutual adjustment, the hazard ratio was 0.81 (0.68-0.97; P trend = 0.02) for
      magnesium and 0.73 (0.63-0.85; P trend <0.0001) for whole grains. CONCLUSIONS:
      These findings indicate that a diet high in magnesium-rich foods, particularly
      whole grains, is associated with a substantially lower risk of type 2 diabetes in
      U.S. black women.

PMID- 17003300
TI  - Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the
      role of obesity.
AB  - OBJECTIVE: Obesity is a well-known risk factor for vitamin D deficiency. We
      evaluated the interrelationship between vitamin D status, body size, and glucose
      homeostasis, measured by HbA1c (A1C). RESEARCH DESIGN AND METHODS: Data are from
      the survey of the 45-year-old 1958 British birth cohort (2002-2004). Information
      on A1C, 25-hydroxyvitamin D [25(OH)D; an indicator of vitamin D status], and BMI
      was collected from 7,198 Caucasian subjects. RESULTS: 25(OH)D was < 75 nmol/l in
      80% of the obese subjects (BMI > or = 30 kg/m2) versus 68% of the other subjects
      (P < 0.0001). Serum 25(OH)D decreased and A1C increased by increasing BMI (P <
      0.0001 for both comparisons). There was a nonlinear association between 25(OH)D
      and A1C: a steep linear decrease in A1C by 25(OH)D until 65 nmol/l and only
      smaller decreases with further increases. There was evidence for effect
      modification by BMI in the association between 25(OH)D and A1C (P < 0.0001), and
      differences appeared stronger for participants with higher compared with lower
      BMIs. After adjustment for sex, season, geographical location, physical activity,
      and social class, percent change in A1C by 10-nmol/l increase in 25(OH)D was 
      0.21 (95% CI -0.31 to -0.11) for BMI < 25 kg/m2, -0.25 (-0.37 to -0.13) for BMI
      25-29.9 kg/m2, -0.65 (-0.95 to -0.34) for BMI 30-34.9 kg/m2, and -1.37 (-2.09 to 
      0.64) for BMI > or = 35 kg/m2. CONCLUSIONS: Body size was a strong determinant
      for 25(OH)D, with concentrations being suboptimal in most obese participants.
      Randomized controlled trials [using dosages sufficient to improve 25(OH)D also
      for the obese] are required to determine whether clinically relevant improvements
      in glucose metabolism can be obtained by vitamin D supplementation.

PMID- 17003301
TI  - Adequacy of glycemic control in hemodialysis patients with diabetes.
AB  - OBJECTIVE: We sought to measure the prevalence of inadequate glycemic control in
      prevalent hemodialysis patients with diabetes and to examine independent
      predictors of inadequate glycemic control in these patients. RESEARCH DESIGN AND
      METHODS: This is a cross-sectional study of prevalent hemodialysis patients with
      diabetes in southeastern Ontario (n = 100). Data were collected by chart review
      and interview. The outcome variable was inadequate glycemic control defined as
      HbA1c (A1C) >0.07. Other measured variables were diabetes type, diabetes
      duration, diabetes physician, blood glucose monitoring, diabetes medications,
      BMI, time on dialysis, and other demographic, clinical, and laboratory variables.
      RESULTS: Fifty-four patients had A1C >0.07. In bivariate analysis, these patients
      had a longer diabetes duration (23.6 vs. 14.7 years, P < 0.001), higher
      proportion with insulin use (81.5 vs. 58.7%, P = 0.012), higher proportion with
      microvascular complications (66.7 vs. 43.5%, P = 0.017), and lower erythropoietin
      (EPO) dose (7.0 vs. 11.9 x 10(3) units/week, P < 0.01) than patients with
      adequate glycemic control. There was no difference between the two groups in
      terms of macrovascular complications (59.3 vs. 65.2%, P = 0.54). In multiple
      logistic regression controlling for age and diabetes type, the diabetes duration
      (odds ratio 1.09 [95% CI 1.04-1.15], P < 0.001), EPO dose (0.90 [0.85-0.97], P <
      0.01), and blood glucose monitoring (10.06 [1.03-98.74], P = 0.05) were the only
      significant independent predictors of A1C >0.07. CONCLUSIONS: A high proportion
      of hemodialysis patients with diabetes had inadequate glycemic control,
      particularly those with longstanding disease. Patients with inadequate glycemic
      control had a significantly higher burden of microvascular complications.

PMID- 17003302
TI  - Mortality and hospitalization in patients after amputation: a comparison between
      patients with and without diabetes.
AB  - OBJECTIVE: We sought to compare the risk of mortality and hospitalization between
      patients with and without diabetes following incident lower-extremity amputation
      (LEA). RESEARCH DESIGN AND METHODS: We performed a retrospective data-linkage
      review of all incident amputations between 1 January 1992 and 31 December 1995.
      Patients were categorized according to their diabetes status. Follow-up for
      mortality was until 1 January 2005 and until 31 March 1996 for hospitalization.
      RESULTS: Of 390 major-incident LEAs performed during the study period, 119
      (30.5%) were in patients with diabetes and 271 (69.5%) were in nondiabetic
      subjects. The median time to death was 27.2 months in patients with diabetes
      compared with 46.7 months for patients without (P = 0.01). Diabetic subjects had
      a 55% greater risk of death than those without diabetes. The risk of developing
      congestive cardiac failure with diabetes was 2.26 (95% CI 1.12-4.57) and of
      further amputation was 1.95 (1.14-3.33) times that of a patient without diabetes
      after incident LEA. CONCLUSIONS: After LEA, patients with diabetes have an
      increased risk of death compared with nondiabetic patients. Efforts should be
      made to minimize these risks with aggressive treatment of cardiovascular risk
      factors and management of cardiac failure.

PMID- 17003303
TI  - Psychological outcomes of patients with screen-detected type 2 diabetes: the
      influence of time since diagnosis and treatment intensity.
AB  - OBJECTIVE: The objective of this study was to investigate how time since
      diagnosis and treatment intensity influence psychological outcomes in patients
      with screen-detected type 2 diabetes. RESEARCH DESIGN AND METHODS: A 2 x 2
      factorial cross-sectional design was used to examine psychological outcomes in
      196 patients with screen-detected diabetes diagnosed 3-33 months previously who
      were receiving usual care or intensive multifactorial pharmacological treatment.
      Outcomes included anxiety, depression, diabetes-related distress, perceived
      seriousness and vulnerability, self-efficacy, and self-care. Multivariate
      analysis was used to examine variations in outcomes based on time since diagnosis
      (<1 vs. 2-3 years) and treatment intensity. RESULTS: Most patients reported
      little distress, low perceived seriousness and vulnerability, high self-efficacy,
      and low self-care, but outcomes varied considerably across conditions. Time
      effects were found for perceived vulnerability, which increases significantly
      with time since diagnosis. Time x treatment interactions were found for anxiety,
      diabetes-related distress, and self-efficacy; notably, intensively treated
      patients showed more distress and less self-efficacy in the 1st year, and usual
      care patients reported more distress and less self-efficacy 2-3 years after
      diagnosis. CONCLUSIONS: Screen-detected patients generally do not experience much
      difficulty with their condition in the first few years, but early and intensive
      treatment can influence patients' psychological outcomes, leading to relatively
      more anxiety and less self-efficacy in the 1st year after diagnosis but not
      necessarily improving self-care. This suggests that intensive treatments confront
      patients with their diabetes earlier on whereas milder treatments may delay
      confrontation. This finding should be taken into account in the development and
      timing of psychological interventions for patients with newly diagnosed diabetes.

PMID- 17003304
TI  - Assessing regimen adherence of adolescents with type 1 diabetes.
AB  - OBJECTIVE: The purpose of this study is to evaluate two updated measures of
      diabetes regimen adherence. The Diabetes Self-Management Profile (DSMP) is a
      widely used, structured interview. Limitations include a substantial interviewer
      and respondent time burden and the need for well-trained interviewers to use
      appropriate prompts and score the open-ended responses. The Diabetes Behavior
      Rating Scale (DBRS) is a self-administered, fixed-choice survey. RESEARCH DESIGN
      AND METHODS: Both measures were administered to 146 youth with type 1 diabetes
      (aged 11-18 years) and their parents. Items were added to the DBRS to allow for
      both flexible and conventional regimens, and the DSMP was modified to use
      standardized wording across items, accommodate flexible regimens, and permit
      administration by nonmedical interviewers. RESULTS: Both measures had good
      evidence of internal consistency (for the DSMP: parent 0.75 and youth 0.70; for
      the DBRS: parent 0.84 and youth 0.84). Scores on the DSMP and the DBRS were
      significantly related (r = 0.72 for parents and 0.74 for youth). There was
      moderate agreement between parent and youth (DSMP, r = 0.51; DBRS, r = 0.48). The
      measures were correlated with HbA1c for both parent (DSMP, r = -0.35; DBRS, r = 
      0.35) and youth (DSMP, r = -0.36; DBRS, r = -0.34) reports. CONCLUSIONS: Both
      measures exhibit good psychometric properties and good criterion validity but
      varied in terms of respondent and interviewer burden, issues that should be
      considered in selecting assessment procedures.

PMID- 17003305
TI  - Brain aging in very old men with type 2 diabetes: the Honolulu-Asia Aging Study.
AB  - OBJECTIVE: Type 2 diabetes leads to cognitive impairment and dementia, which may
      reflect microvascular and macrovascular complications as well as
      neurodegenerative processes. There are few studies on the anatomical basis for
      loss of cognitive function in type 2 diabetes. The objective of this study was to
      investigate the association between type 2 diabetes and markers of brain aging on
      magnetic resonance images, including infarcts, lacunes, and white matter
      hyperintensities as markers of vascular damage and general and hippocampal
      atrophy as markers of neurodegeneration in Japanese-American men born between
      1900 and 1919 and followed since 1965 in the Honolulu-Asia Aging Study. RESEARCH
      DESIGN AND METHODS: Prevalent and incident dementia was assessed. Associations
      between magnetic resonance imaging markers and diabetic status were estimated
      with logistic regression, controlling for sociodemographic and other vascular
      factors. RESULTS: The prevalence of type 2 diabetes in the cohort is 38%.
      Subjects with type 2 diabetes had a moderately elevated risk for lacunes (odds
      ratio [OR] 1.6 [95% CI 1.0-2.6]) and hippocampal atrophy (1.7 [0.9-2.9]). The
      risk for both hippocampal atrophy and lacunes/infarcts was twice as high in
      subjects with compared with those without type 2 diabetes. Among the group with
      type 2 diabetes, those with the longest duration of diabetes, those taking
      insulin, and those with complications had relatively more pathologic brain
      changes. CONCLUSIONS: There is evidence that older individuals with type 2
      diabetes have an elevated risk for vascular brain damage and neurodegenerative
      changes. These pathological changes may be the anatomical basis for an increased
      risk of cognitive impairment or dementia in type 2 diabetes.

PMID- 17003306
TI  - The effect of pioglitazone on the liver: role of adiponectin.
AB  - OBJECTIVE: Diabetic hyperglycemia results from insulin resistance of peripheral
      tissues and glucose overproduction due to increased gluconeogenesis (GNG).
      Thiazolidinediones (TZDs) improve peripheral insulin sensitivity, but the effect
      on the liver is less clear. The goal of this study was to examine the effect of
      TZDs on GNG. RESEARCH DESIGN AND METHODS: Twenty sulfonylurea-treated type 2
      diabetic subjects were randomly assigned (double-blind study) to receive
      pioglitazone (PIO group; 45 mg/day) or placebo (Plc group) for 4 months to assess
      endogenous glucose production (EGP) (3-(3)H-glucose infusion), GNG (D2O
      technique), and insulin sensitivity by two-step hyperinsulinemic-euglycemic clamp
      (240 and 960 pmol/min per m2). RESULTS: Fasting plasma glucose (FPG) (10.0 +/-
      0.8 to 7.7 +/- 0.7 mmol/l) and HbA1c (9.0 +/- 0.4 to 7.3 +/- 0.6%) decreased in
      the PIO and increased in Plc group (P < 0.05 PIO vs. Plc). Insulin sensitivity
      increased approximately 40% during high insulin clamp after pioglitazone (P <
      0.01) and remained unchanged in the Plc group (P < 0.05 PIO vs. Plc). EGP did not
      change, while GNG decreased in the PIO group (9.6 +/- 0.7 to 8.7 +/- 0.6 micromol
      x min(-1) x kg(ffm)(-1)) and increased in the Plc group (8.0 +/- 0.5 to 9.6 +/-
      0.8) (P < 0.05 PIO vs. Plc). Change in FPG correlated with change in GNG flux (r
      = 0.63, P < 0.003) and in insulin sensitivity (r = 0.59, P < 0.01). Plasma
      adiponectin increased after pioglitazone (P < 0.001) and correlated with delta
      FPG (r = -0.54, P < 0.03), delta GNG flux (r = -0.47, P < 0.05), and delta
      insulin sensitivity (r = 0.65, P < 0.005). Plasma free fatty acids decreased
      after pioglitazone and correlated with delta GNG flux (r = 0.54, P < 0.02). From
      stepwise regression analysis, the strongest determinant of change in FPG was
      change in GNG flux. CONCLUSIONS: Pioglitazone improves FPG, primarily by reducing
      GNG flux in type 2 diabetic subjects.

PMID- 17003307
TI  - Modeling chronic glycemic exposure variables as correlates and predictors of
      microvascular complications of diabetes.
AB  - OBJECTIVE: The degree to which chronic glycemic exposure (CGE) (fasting plasma
      glucose [FPG], HbA1c [A1C], duration of diabetes, age at onset of diabetes, or
      combinations of these) is associated with or predicts the severity of microvessel
      complications is unsettled. Specifically, we test whether combinations of
      components correlate and predict complications better than individual components.
      RESEARCH DESIGN AND METHODS: Correlations and predictions of CGE and
      complications were assessed in the Rochester Diabetic Neuropathy Study, a
      population-based, cross-sectional, and longitudinal epidemiologic survey of 504
      patients with diabetes followed for up to 20 years. RESULTS: In multivariate
      analysis, A1C and duration of diabetes (and to a lesser degree age at onset of
      diabetes but not FPG) were the main significant CGE risk covariates for
      complications. A derived glycemic exposure index (GE(i)) correlated with and
      predicted complications better than did individual components. Composite or
      staged measures of polyneuropathy provided higher correlations and better
      predictions than did dichotomous measures of whether polyneuropathy was present
      or not. Generally, the mean GE(i) was significantly higher with increasing stages
      of severity of complications. CONCLUSIONS: A combination of A1C, duration of
      diabetes, and age at onset of diabetes (a mathematical index, GE(i)) correlates
      significantly with complications and predicts later complications better than
      single components of CGE. Serial measures of A1C improved the correlations and
      predictions. For polyneuropathy, continuous or staged measurements performed
      better than dichotomous judgments. Even with intensive assessment of CGE and
      complications over long times, only about one-third of the variability of the
      severity of complications is explained, emphasizing the role of other putative
      risk covariates.

PMID- 17003308
TI  - Low testosterone and high C-reactive protein concentrations predict low
      hematocrit in type 2 diabetes.
AB  - OBJECTIVE: After the demonstration that one-third of male patients with type 2
      diabetes have hypogonadotrophic hypogonadism, we have shown that patients with
      hypogonadotrophic hypogonadism also have markedly elevated C-reactive protein
      (CRP) concentrations. We have now hypothesized that type 2 diabetic subjects with
      hypogonadotrophic hypogonadism may have a lower hematocrit because testosterone
      stimulates, whereas chronic inflammation suppresses, erythropoiesis. RESEARCH
      DESIGN AND METHODS: Seventy patients with type 2 diabetes at a tertiary referral
      center were included in this study. RESULTS: The mean hematocrit in patients with
      hypogonadotrophic hypogonadism (n = 37), defined as calculated free testosterone
      (cFT) of <6.5 ng/dl, was 40.6 +/- 1.1%, whereas that in eugonadal patients (n =
      33) was 43.3 +/- 0.7% (P = 0.011). The hematocrit was related to cFT
      concentration (r = 0.46; P < 0.0001); it was inversely related to plasma CRP
      concentration (r = 0.41; P < 0.0004). Patients with CRP <3 mg/l had a higher
      hematocrit (42.7 +/- 0.7%) than those with CRP >3 mg/l (39.9 +/- 1.1%; P < 0.05).
      The prevalence of normocytic normochromic anemia (hemoglobin <13 g/dl) was 23% in
      the entire group, whereas it was 37.8% in the men with hypogonadotrophic
      hypogonadism and 3% in the eugonadal men (P < 0.01). Erythropoietin concentration
      was elevated or high normal in all 11 patients with anemia in whom it was tested.
      CONCLUSIONS: We conclude that hypogonadotrophic hypogonadism in male type 2
      diabetic subjects is associated with a lower hematocrit and a frequent occurrence
      of mild normocytic normochromic anemia with normal or high erythropoietin
      concentrations. In these patients, hematocrit is also inversely related to CRP
      concentration. Thus, low testosterone and chronic inflammatory mechanisms may
      contribute to mild anemia. Such patients may also have a high risk of
      atherosclerotic cardiovascular events in view of their markedly elevated CRP
      concentrations.

PMID- 17003309
TI  - The xylosyltransferase I gene polymorphism c.343G>T (p.A125S) is a risk factor
      for diabetic nephropathy in type 1 diabetes.
AB  - OBJECTIVE: Xylosyltransferase I (XT-I) is the chain-initiating enzyme in the
      biosynthesis of proteoglycans in basement membranes. It catalyzes the transfer of
      xylose to selected serine residues in the core protein. The XYLT-II gene codes
      for a protein highly homologous to XT-I. Proteoglycans are important components
      of basement membranes and are responsible for their permeability properties. Type
      1 diabetic patients have an altered proteoglycan metabolism, which results in
      microvascular complications. Thus, genetic variations in the xylosyltransferase
      genes might be implicated in the initiation and progression of these
      complications. RESEARCH DESIGN AND METHODS: Genotyping of four genetic variations
      in the genes XYLT-I and XYLT-II was performed in 912 type 1 diabetic patients
      (453 with and 459 without diabetic nephropathy) using restriction fragment-length
      polymorphism. RESULTS: The distribution of the c.343G>T polymorphism in XYLT-I is
      significantly different between patients with and without diabetic nephropathy (P
      = 0.03). T-alleles were more frequent in patients with diabetic nephropathy (odds
      ratio 2.47 [95% CI 1.04-5.83]). The allelic frequencies of the other investigated
      XYLT-I and XYLT-II variations (XYLT-I: c.1989T>C in exon 9; XYLT-II: IVS6-9T>C
      and IVS6-14_IVS6-13insG in intron 5; and c.2402C>G: p.T801R in exon 11) were not
      different between patients with and without diabetic nephropathy. CONCLUSIONS:
      The XYLT-I c.343G>T polymorphism contributes to the genetic susceptibility to
      development of diabetic nephropathy in type 1 diabetic patients.

PMID- 17003310
TI  - Cholesterol absorption and synthesis in children with type 1 diabetes.
AB  - OBJECTIVE: The levels of the surrogate markers of cholesterol absorption
      (cholestanol and plant sterols) and synthesis (cholesterol precursors) in serum
      have suggested that in adult type 1 diabetes, cholesterol absorption is high and
      synthesis is low compared with type 2 diabetic or control subjects. Accordingly,
      these findings were further studied in children with type 1 diabetes. RESEARCH
      DESIGN AND METHODS: Forty-eight children with diabetes were compared with 79 age-
      and sex-matched control subjects. The serum ratios of cholesterol absorption and
      synthesis markers were measured with gas-liquid chromatography. The study
      population was divided into triads (combining the two lowest triads) by serum
      cholestanol ratios of the control subjects indicating low to high cholesterol
      absorption efficiency. RESULTS: The ratios of the absorption and synthesis
      markers were similar in case and control subjects, and they were negatively
      related to each other in control subjects, being less consistent in diabetic
      patients. Thus, high cholesterol absorption was associated with low synthesis.
      Plant sterol ratios increased significantly with increasing cholestanol triads in
      both groups, but the values in the lowest triads were higher in case versus
      control subjects. CONCLUSIONS: Homeostasis between cholesterol absorption and
      synthesis is maintained in control children and somewhat less consistently in
      those with diabetes. The higher plant sterol ratios in diabetic versus control
      subjects in the lowest cholestanol triads suggest that cholesterol absorption is
      higher in children with diabetes versus control subjects but only within the
      range of low cholesterol absorption.

PMID- 17003311
TI  - High plasma concentration of remnant lipoprotein cholesterol in obese children
      and adolescents.
AB  - OBJECTIVE: Remnant lipoproteins (RLPs) are the products of the lipolytic
      degradation of triglyceride-rich lipoproteins produced by the liver and
      intestine. Recent studies have demonstrated that RLPs are correlated with
      cardiovascular risk. We assessed the relationship between obesity and RLP and
      evaluated the factors related to RLP in children and adolescents. RESEARCH DESIGN
      AND METHODS: We measured BMI, waist circumference, blood pressure, body fat mass,
      total abdominal fat, visceral and subcutaneous fat areas, fasting glucose,
      insulin, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and
      RLP cholesterol in 135 children and adolescents (67 boys and 68 girls). Plasma
      RLP fractions were isolated using an immunoaffinity gel containing specific anti
      apolipoprotein (apo) B-100 and anti-apoA-I antibodies. Based on the BMI
      percentile, the subjects were divided into two groups: normal (< 85th percentile)
      and overweight (> or = 85th percentile). RESULTS: RLP cholesterol was
      significantly correlated with age, sex, BMI, waist circumference, systolic and
      diastolic blood pressures, visceral and subcutaneous fat areas, visceral-to
      subcutaneous fat area ratio, total cholesterol, triglycerides, HDL cholesterol,
      apoB, and homeostasis model assessment of insulin resistance (HOMA-IR). According
      to the multivariate regression analysis, triglycerides (beta = 0.928, P < 0.001)
      were independently correlated with RLP cholesterol. After excluding lipid
      profiles as an independent variable, the multivariate regression analysis
      revealed that HOMA-IR (beta = 0.231, P = 0.007) and systolic blood pressure (beta
      = 0.169, P = 0.046) were independently associated with RLP cholesterol.
      CONCLUSIONS: RLP cholesterol was significantly higher in obese children and
      adolescents. Triglycerides, systolic blood pressure, and insulin resistance were
      related to RLP cholesterol.

PMID- 17003312
TI  - Premeal insulin treatment during basal-bolus regimen in young children with type
      1 diabetes.

PMID- 17003313
TI  - A high-carbohydrate, high-fiber meal improves endothelial function in adults with
      the metabolic syndrome.

PMID- 17003314
TI  - Effect of a single bout of prior moderate exercise on cutaneous perfusion in type
      2 diabetes.

PMID- 17003315
TI  - Gut hormones and related concepts.

PMID- 17003316
TI  - Severity of autonomic and sensory neuropathy and the impairment of visual- and
      auditory-evoked potentials in type 1 diabetes: is there a relationship?

PMID- 17003317
TI  - Use of repaglinide during the first weeks of pregnancy in two type 2 diabetic
      women.

PMID- 17003318
TI  - Higher rate of obesity and hypertension in adolescents with type 2 diabetes than
      in those with type 1 diabetes.

PMID- 17003319
TI  - Decreased high-molecular weight adiponectin-to-total adiponectin ratio in sera is
      associated with insulin resistance in Japanese metabolically obese, normal-weight
      men with normal glucose tolerance.

PMID- 17003320
TI  - A patient with extreme insulin resistance syndrome treated with pioglitazone.

PMID- 17003321
TI  - Reversibility of antipsychotic treatment-related diabetes in patients with
      schizophrenia: a case series of switching to aripiprazole.

PMID- 17003322
TI  - A continuous metabolic syndrome risk score: utility for epidemiological analyses.

PMID- 17003323
TI  - Ovarian stockpiling in polycystic ovary syndrome, infertility, and the combined
      use of rosiglitazone and metformin.

PMID- 17003324
TI  - Triple therapy in type 2 diabetes: insulin glargine or rosiglitazone added to
      combination therapy of sulfonylurea plus metformin in insulin-naive patients:
      response to Rosenstock et al.

PMID- 17003325
TI  - An open, randomized, parallel-group study to compare the efficacy and safety
      profile of inhaled human insulin (Exubera) with meformin as adjunctive therapy in
      patients with type 2 diabetes poorly controlled on a sulfonylurea: response to
      Barnett et al.

PMID- 17003329
TI  - Antihypertensive medications and the risk of incident type 2 diabetes: response
      to Taylor et al.

PMID- 17003330
TI  - Leptin deficiency unmasks the deleterious effects of impaired peroxisome
      proliferator-activated receptor gamma function (P465L PPARgamma) in mice.
AB  - Peroxisome proliferator-activated receptor (PPAR)gamma is a key transcription
      factor facilitating fat deposition in adipose tissue through its proadipogenic
      and lipogenic actions. Human patients with dominant-negative mutations in
      PPARgamma display lipodystrophy and extreme insulin resistance. For this reason
      it was completely unexpected that mice harboring an equivalent mutation (P465L)
      in PPARgamma developed normal amounts of adipose tissue and were insulin
      sensitive. This finding raised important doubts about the interspecies
      translatability of PPARgamma-related findings, bringing into question the
      relevance of other PPARgamma murine models. Here, we demonstrate that when
      expressed on a hyperphagic ob/ob background, the P465L PPARgamma mutant grossly
      exacerbates the insulin resistance and metabolic disturbances associated with
      leptin deficiency, yet reduces whole-body adiposity and adipocyte size. In mouse,
      coexistence of the P465L PPARgamma mutation and the leptin-deficient state
      creates a mismatch between insufficient adipose tissue expandability and
      excessive energy availability, unmasking the deleterious effects of PPARgamma
      mutations on carbohydrate metabolism and replicating the characteristic clinical
      symptoms observed in human patients with dominant-negative PPARgamma mutations.
      Thus, adipose tissue expandability is identified as an important factor for the
      development of insulin resistance in the context of positive energy balance.

PMID- 17003331
TI  - Bradykinin augments insulin-stimulated glucose transport in rat adipocytes via
      endothelial nitric oxide synthase-mediated inhibition of Jun NH2-terminal kinase.
AB  - An increase in bradykinin has been suggested to contribute to the enhanced
      insulin sensitivity observed in the presence of ACE inhibitors. To investigate a
      potential direct, nonvascular effect on an insulin target tissue, the effect of
      bradykinin on glucose uptake and insulin signaling was studied in primary rat
      adipocytes. Whereas basal glucose uptake was not altered, bradykinin augmented
      insulin-stimulated glucose uptake twofold, which was blocked by HOE-140, a
      bradykinin B2 receptor antagonist. The bradykinin effect on glucose uptake was
      nitric oxide (NO) dependent, mimicked by NO donors and absent in adipocytes from
      endothelial NO synthase-/- mice. Investigation of insulin signaling revealed that
      bradykinin enhanced insulin receptor substrate-1 (IRS-1) Tyr phosphorylation,
      Akt/protein kinase B phosphorylation, and GLUT4 translocation. In contrast,
      insulin-stimulated extracellular signal-regulated kinase1/2 and Jun NH2-terminal
      kinase (JNK) activation were decreased in the presence of bradykinin, accompanied
      by decreased IRS-1 Ser307 phosphorylation. Furthermore, bradykinin did not
      enhance insulin action in the presence of the JNK inhibitor, SP-600125, or in
      adipocytes from JNK1-/- mice. These data indicate that bradykinin enhances
      insulin sensitivity in adipocytes via an NO-dependent pathway that acts by
      modulating the feedback inhibition of insulin signaling at the level of IRS-1.

PMID- 17003332
TI  - Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose
      uptake and fatty acid oxidation in vitro via AMP-activated protein kinase.
AB  - Although interleukin-6 (IL-6) has been associated with insulin resistance, little
      is known regarding the effects of IL-6 on insulin sensitivity in humans in vivo.
      Here, we show that IL-6 infusion increases glucose disposal without affecting the
      complete suppression of endogenous glucose production during a hyperinsulinemic
      euglycemic clamp in healthy humans. Because skeletal muscle accounts for most of
      the insulin-stimulated glucose disposal in vivo, we examined the mechanism(s) by
      which IL-6 may affect muscle metabolism using L6 myotubes. IL-6 treatment
      increased fatty acid oxidation, basal and insulin-stimulated glucose uptake, and
      translocation of GLUT4 to the plasma membrane. Furthermore, IL-6 rapidly and
      markedly increased AMP-activated protein kinase (AMPK). To determine whether the
      activation of AMPK mediated cellular metabolic events, we conducted experiments
      using L6 myotubes infected with dominant-negative AMPK alpha-subunit. The effects
      described above were abrogated in AMPK dominant-negative-infected cells. Our
      results demonstrate that acute IL-6 treatment enhances insulin-stimulated glucose
      disposal in humans in vivo, while the effects of IL-6 on glucose and fatty acid
      metabolism in vitro appear to be mediated by AMPK.

PMID- 17003333
TI  - Impaired adipose tissue development in mice with inactivation of placental growth
      factor function.
AB  - Placental growth factor (PlGF)-deficient (PlGF-/-) and wild-type mice were kept
      on a standard-fat or high-fat diet for 15 weeks. With the standard-fat diet, the
      body weights of PlGF-/- and wild-type mice were comparable, whereas the combined
      weight of subcutaneous and gonadal adipose tissues was lower in PlGF-/- mice (P =
      0.02). With the high-fat diet, PlGF-/- mice had a lower body weight (P < 0.05)
      and less total subcutaneous plus gonadal adipose tissue (P < 0.0001). Blood
      vessel size was lower in gonadal adipose tissue of PlGF-/- mice with both the
      standard-fat and high-fat diet (P < 0.05). Blood vessel density, normalized to
      adipocyte number, was significantly lower in subcutaneous adipose tissue of PlGF
      /- mice fed the high-fat diet (P < 0.01). De novo adipose tissue development in
      nude mice injected with 3T3-F442A preadipocytes was reduced (P < 0.005) by
      administration of a PlGF-neutralizing antibody. Bone marrow transplantation from
      wild-type or PlGF-/- mice to wild-type or PlGF-/- recipient mice revealed
      significantly lower blood vessel density in PlGF-/- recipient mice without an
      effect on adipose tissue growth. Thus, in murine models of diet-induced obesity,
      inactivation of PlGF impairs adipose tissue development, at least in part as a
      result of reduced angiogenesis.

PMID- 17003334
TI  - STAT5 activity in pancreatic beta-cells influences the severity of diabetes in
      animal models of type 1 and 2 diabetes.
AB  - Pancreatic beta-cell growth and survival and insulin production are stimulated by
      growth hormone and prolactin through activation of the transcription factor
      signal transducer and activator of transcription (STAT)5. To assess the role of
      STAT5 activity in beta-cells in vivo, we generated transgenic mice that expressed
      a dominant-negative mutant of STAT5a (DNSTAT5) or constitutive active mutant of
      STAT5b (CASTAT5) under control of the rat insulin 1 promoter (RIP). When
      subjected to a high-fat diet, RIP-DNSTAT5 mice showed higher body weight,
      increased plasma glucose levels, and impairment of glucose tolerance, whereas RIP
      CASTAT5 mice were more glucose tolerant and less hyperleptinemic than wild-type
      mice. Although the pancreatic insulin content and relative beta-cell area were
      increased in high-fat diet-fed RIP-DNSTAT5 mice compared with wild-type or RIP
      CASTAT5 mice, RIP-DNSTAT5 mice showed reduced beta-cell proliferation at 6 months
      of age. The inhibitory effect of high-fat diet or leptin on insulin secretion was
      diminished in isolated islets from RIP-DNSTAT5 mice compared with wild-type
      islets. Upon multiple low-dose streptozotocin treatment, RIP-DNSTAT5 mice
      exhibited higher plasma glucose levels, lower plasma insulin levels, and lower
      pancreatic insulin content than wild-type mice, whereas RIP-CASTAT5 mice
      maintained higher levels of plasma insulin. In conclusion, our results indicate
      that STAT5 activity in beta-cells influences the susceptibility to experimentally
      induced type 1 and type 2 diabetes.

PMID- 17003336
TI  - Impact of defined matrix interactions on insulin production by cultured human
      beta-cells: effect on insulin content, secretion, and gene transcription.
AB  - The impact of extracellular matrix on insulin production needs to be understood
      both to optimize the derivation of functional beta-cells for transplantation and
      to understand mechanisms controlling islet neogenesis and glucose homeostasis. In
      this study, we present evidence that adhesion to some common matrix constituents
      has a profound impact on the transcription, secretion, and storage of insulin by
      human beta-cells. The integrin-dependent adhesion of fetal beta-cells to both
      collagen IV and vitronectin induces significant glucose-independent insulin
      secretion and a substantial reciprocal decline in insulin content. Collagen IV,
      but not vitronectin, induces comparable responses in adult beta-cells. Inhibition
      of extracellular signal-regulated kinase activation abrogates matrix-induced
      insulin secretion and effectively preserves the insulin content of adherent beta
      cells. Using real-time PCR, we demonstrate that adhesion of both fetal and adult
      beta-cells to collagen IV and vitronectin also results in the marked suppression
      of insulin gene transcription. Based on these findings, we contend that integrin
      dependent adhesion and signaling in response to certain matrices can have a
      significant negative impact on insulin production by primary human beta-cells.
      Such responses were not found to be associated with cell death but may precede
      beta-cell dedifferentiation.

PMID- 17003335
TI  - Low concentration of interleukin-1beta induces FLICE-inhibitory protein-mediated
      beta-cell proliferation in human pancreatic islets.
AB  - High glucose concentrations have a dual effect on beta-cell turnover, inducing
      proliferation in the short-term and apoptosis in the long-term. Hyperglycemia
      leads to beta-cell production of interleuking (IL)-1beta in human pancreatic
      islets. Fas, a death receptor regulated by IL-1beta, is involved in glucose
      induced beta-cell apoptosis. Fas engagement can be switched from death signal to
      induction of proliferation when the caspase 8 inhibitor, FLICE-inhibitory protein
      (FLIP), is active. Here, we show that IL-1beta at low concentrations may
      participate in the mitogenic actions of glucose through the Fas-FLIP pathway.
      Thus, exposure of human islets to low IL-1beta concentrations (0.01-0.02 ng/ml)
      stimulated proliferation and decreased apoptosis, whereas increasing amounts of
      IL-1beta (2-5 ng/ml) had the reverse effects. A similarly bimodal induction of
      FLIP, pancreatic duodenal homeobox (PDX)-1, and Pax4 mRNA expression, as well as
      glucose-stimulated insulin secretion, was observed. In contrast, Fas induction by
      IL-1beta was monophasic. Low IL-1beta also induced the IL-1 receptor antagonist
      (IL-1Ra), suppression of which by RNA interference abrogated the beneficial
      effects of low IL-1beta. The Fas antagonistic antibody ZB4 and small interfering
      RNA to FLIP prevented low IL-1beta-stimulated beta-cell proliferation. Consistent
      with our in vitro results, IL-1beta knockout mice displayed glucose intolerance
      along with a decrease in islet Fas, FLIP, Pax4, and PDX-1 transcripts. These
      findings indicate that low IL-1beta levels positively influence beta-cell
      function and turnover through the Fas-FLIP pathway and that IL-1Ra production
      prevents harmful effects of high IL-1beta concentrations.

PMID- 17003337
TI  - Foxa1-deficient mice exhibit impaired insulin secretion due to uncoupled
      oxidative phosphorylation.
AB  - Foxa1 (formerly hepatic nuclear factor 3alpha) belongs to the family of Foxa
      genes that are expressed in early development and takes part in the
      differentiation of endoderm-derived organs and the regulation of glucose
      homeostasis. Foxa1-/- pups are growth retarded and hypoglycemic but glucose
      intolerant in response to an intraperitoneal glucose challenge. However, the
      mechanism of glucose intolerance in this model has not been investigated. Here,
      we show that Foxa1-/- islets exhibit decreased glucose-stimulated insulin release
      in islet perifusion experiments and have significantly reduced pancreatic insulin
      and glucagon content. Moreover, Foxa1-/- beta-cells exhibit attenuated calcium
      influx in response to glucose and glyburide, suggesting an insulin secretion
      defect either at the level or upstream of the ATP-sensitive K+ channel.
      Intracellular ATP levels after incubation with 10 mmol/l glucose were about 2.5
      times lower in Foxa1-/- islets compared with controls. This diminished ATP
      synthesis could be explained by increased expression of the mitochondrial
      uncoupling protein uncoupling protein 2 (UCP2) in Foxa1-deficient islets,
      resulting in partially uncoupled mitochondria. Chromatin immunoprecipitation
      assays indicate that UCP2 is a direct transcriptional target of Foxa1 in vivo.
      Thus, we have identified a novel function for Foxa1 in the regulation of
      oxidative phosphorylation in pancreatic beta-cells.

PMID- 17003338
TI  - Suppressed insulin signaling and increased apoptosis in CD38-null islets.
AB  - CD38 is a multifunctional enzyme capable of generating metabolites that release
      Ca2+ from intracellular stores, including nicotinic acid adenine dinucleotide
      phosphate (NAADP). A number of studies have led to the controversial proposal
      that CD38 mediates an alternate pathway for glucose-stimulated insulin release
      and contributes to the pathogenesis of diabetes. It has recently been shown that
      NAADP mediates Ca2+ mobilization by insulin in human pancreatic beta-cells. In
      the present study, we report altered Ca2+ homeostasis and reduced responsiveness
      to insulin, but not glucose, in Cd38-/- beta-cells. In keeping with the
      antiapoptotic role of insulin signaling, Cd38-/- islets were significantly more
      susceptible to apoptosis compared with islets isolated from littermate controls.
      This finding correlated with disrupted islet architecture and reduced beta-cell
      mass in Cd38-/- mice, both in the context of a normal lab diet and a high-fat
      diet. Nevertheless, we did not find robust differences in glucose homeostasis in
      vivo or glucose signaling in vitro in Cd38-/- mice on the C57BL/6 genetic
      background, in contrast to previous studies by others of Cd38 knockout mice on
      the ICR background. Thus, our results suggest that CD38 plays a role in novel
      antiapoptotic signaling pathways but does not directly control glucose signaling
      in pancreatic beta-cells.

PMID- 17003339
TI  - Altered gene expression related to glomerulogenesis and podocyte structure in
      early diabetic nephropathy of db/db mice and its restoration by pioglitazone.
AB  - Glomerular injury plays a pivotal role in the development of diabetic
      nephropathy. To elucidate molecular mechanisms underlying diabetic
      glomerulopathy, we compared glomerular gene expression profiles of db/db mice
      with those of db/m control mice at a normoalbuminuric stage characterized by
      hyperglycemia and at an early stage of diabetic nephropathy with elevated
      albuminuria, using cDNA microarray. In db/db mice at the normoalbuminuric stage,
      hypoxia-inducible factor-1alpha (HIF-1alpha), ephrin B2, glomerular epithelial
      protein 1, and Pod-1, which play key roles in glomerulogenesis, were already
      upregulated in parallel with an alteration of genes related to glucose
      metabolism, lipid metabolism, and oxidative stress. Podocyte structure-related
      genes, actinin 4alpha and dystroglycan 1 (DG1), were also significantly
      upregulated at an early stage. The alteration in the expression of these genes
      was confirmed by quantitative RT-PCR. Through pioglitazone treatment, gene
      expression of ephrin B2, Pod-1, actinin 4alpha, and DG1, as well as that of
      oxidative stress and lipid metabolism, was restored concomitant with attenuation
      of albuminuria. In addition, HIF-1alpha protein expression was partially
      attenuated by pioglitazone. These results suggest that not only metabolic
      alteration and oxidative stress, but also the alteration of gene expression
      related to glomerulogenesis and podocyte structure, may be involved in the
      pathogenesis of early diabetic glomerulopathy in type 2 diabetes.

PMID- 17003340
TI  - A selective aldose reductase inhibitor of a new structural class prevents or
      reverses early retinal abnormalities in experimental diabetic retinopathy.
AB  - Previously studied inhibitors of aldose reductase were largely from two chemical
      classes, spirosuccinamide/hydantoins and carboxylic acids. Each class has its own
      drawbacks regarding selectivity, in vivo potency, and human safety; as a result,
      the pathogenic role of aldose reductase in diabetic retinopathy remains
      controversial. ARI-809 is a recently discovered aldose reductase inhibitor (ARI)
      of a new structural class, pyridazinones, and has high selectivity for aldose
      versus aldehyde reductase. To further test the possible pathogenic role of aldose
      reductase in the development of diabetic retinopathy, we examined the retinal
      effects of this structurally novel and highly selective ARI in insulinized
      streptozotocin-induced diabetic rats. ARI-809 treatment was initiated 1 month
      after diabetes induction and continued for 3 months at a dose that inhibited the
      polyol pathway in the retina of diabetic rats to a similar extent as sorbinil, a
      poorly selective hydantoin ARI previously shown to prevent retinopathy in this
      model. ARI-809 improved survival, inhibited cataract development, normalized
      retinal sorbitol and fructose, and protected the retina from abnormalities that
      also occur in human diabetes: neuronal apoptosis, glial reactivity, and
      complement deposition. Because ARI-809 is a novel chemotype highly selective for
      aldose reductase, these results support the notion that aldose reductase is the
      key relay that converts hyperglycemia into glucose toxicity in neural and glial
      cell types in the retina.

PMID- 17003341
TI  - Common haplotypes at the adiponectin receptor 1 (ADIPOR1) locus are associated
      with increased risk of coronary artery disease in type 2 diabetes.
AB  - Adiponectin, an adipokine facilitating insulin action, has antiatherogenic
      effects. This study investigated whether common polymorphisms in the adiponectin
      receptor 1 (ADIPOR1) gene mediating these effects influence the risk of coronary
      artery disease (CAD) in type 2 diabetes. Linkage disequilibrium analysis of 28
      single nucleotide polymorphisms (SNPs) spanning the entire ADIPOR1 locus revealed
      two haplotype blocks that could be tagged by six SNPs. These six markers were
      typed in two populations of CAD-positive and -negative subjects with type 2
      diabetes, one from Boston (n = 411) and the other from Italy (n = 533). In the
      Boston population, the three tags of the more 3' block were all significantly
      associated with CAD (P = 0.001-0.01). A similar trend, although not significant,
      was found in Italian subjects. Haplotype analysis of the combined populations
      revealed different haplotype distributions in case and control subjects (P =
      0.0002), with one common haplotype being associated in homozygotes with a greater
      than threefold increase in cardiovascular risk (odds ratio 3.6 [95% CI 1.8-7.2]).
      Some of the genotypes associated with increased cardiovascular risk were
      associated with 30-40% lower ADIPOR1 mRNA levels in blood mononuclear cells (n =
      60) and adipose tissue biopsies (n = 28) (P = 0.001-0.014). Our findings point to
      genetic variability at the ADIPOR1 locus as a strong determinant of CAD
      susceptibility in type 2 diabetes.

PMID- 17003342
TI  - Mechanisms of the depot specificity of peroxisome proliferator-activated receptor
      gamma action on adipose tissue metabolism.
AB  - In this study, we aimed to establish the mechanisms whereby peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonism brings about
      redistribution of fat toward subcutaneous depots and away from visceral fat. In
      rats treated with the full PPARgamma agonist COOH (30 mg x kg(-1) x day(-1)) for
      3 weeks, subcutaneous fat mass was doubled and that of visceral fat was reduced
      by 30% relative to untreated rats. Uptake of triglyceride-derived nonesterified
      fatty acids was greatly increased in subcutaneous fat (14-fold) and less so in
      visceral fat (4-fold), with a concomitant increase, restricted to subcutaneous
      fat only, in mRNA levels of the uptake-, retention-, and esterification-promoting
      enzymes lipoprotein lipase, aP2, and diacylglycerol acyltransferase 1. Basal
      lipolysis and fatty acid recycling were stimulated by COOH in both subcutaneous
      fat and visceral fat, with no frank quantitative depot specificity. The agonist
      increased mRNA levels of enzymes of fatty acid oxidation and thermogenesis much
      more strongly in visceral fat than in subcutaneous fat, concomitantly with a
      stronger elevation in O2 consumption in the former than in the latter.
      Mitochondrial biogenesis was stimulated equally in both depots. These findings
      demonstrate that PPARgamma agonism redistributes fat by stimulating the lipid
      uptake and esterification potential in subcutaneous fat, which more than
      compensates for increased O2 consumption; conversely, lipid uptake is minimally
      altered and energy expenditure is greatly increased in visceral fat, with
      consequent reduction in fat accumulation.

PMID- 17003343
TI  - Palmitate-mediated downregulation of peroxisome proliferator-activated receptor
      gamma coactivator 1alpha in skeletal muscle cells involves MEK1/2 and nuclear
      factor-kappaB activation.
AB  - The mechanisms by which elevated levels of free fatty acids cause insulin
      resistance are not well understood. Previous studies have reported that insulin
      resistant states are characterized by a reduction in the expression of peroxisome
      proliferator-activated receptor-gamma coactivator (PGC)-1, a transcriptional
      activator that promotes oxidative capacity in skeletal muscle cells. However,
      little is known about the factors responsible for reduced PGC-1 expression. The
      expression of PGC-1 mRNA levels was assessed in C2C12 skeletal muscle cells
      exposed to palmitate either in the presence or in the absence of several
      inhibitors to study the biochemical pathways involved. We report that exposure of
      C2C12 skeletal muscle cells to 0.75 mmol/l palmitate, but not oleate, reduced PGC
      1alpha mRNA levels (66%; P < 0.001), whereas PGC-1beta expression was not
      affected. Palmitate led to mitogen-activated protein kinase (MAPK)-extracellular
      signal-related kinase (ERK) 1/2 (MEK1/2) activation. In addition, pharmacological
      inhibition of this pathway by coincubation of the palmitate-exposed cells with
      the MEK1/2 inhibitors PD98059 and U0126 prevented the downregulation of PGC
      1alpha. Furthermore, nuclear factor-kappaB (NF-kappaB) activation was also
      involved in palmitate-mediated PGC-1alpha downregulation, since the NF-kappaB
      inhibitor parthenolide prevented a decrease in PGC-1alpha expression. These
      findings indicate that palmitate reduces PGC-1alpha expression in skeletal muscle
      cells through a mechanism involving MAPK-ERK and NF-kappaB activation.

PMID- 17003344
TI  - Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic
      insulin action.
AB  - IGF-I is recognized as an insulin sensitizer at the liver and muscle, while
      recent evidence suggests that IGF-binding protein (IGFBP)-3 acts as an insulin
      antagonist. As there is a paucity of IGF-I receptors in the liver and as the IGF
      IGFBP system in the central nervous system is emerging as physiologically
      relevant, we examined whether the effects of IGF-I and IGFBP-3 on insulin action
      are mediated through central mechanisms. Intracerebroventricular (ICV) infusion
      of IGF-I during the insulin clamp (3 mU x kg(-1) x min(-1)) resulted in
      significant improvement in hepatic insulin action (50%, P < 0.05). In contrast,
      ICV infusion of IGFBP-3 significantly impaired insulin action at the liver (45%
      increase in hepatic glucose production, P < 0.01). While IGF-I marginally
      increased peripheral glucose uptake, IGFBP-3 significantly decreased peripheral
      glucose uptake (approximately 30%, P < 0.01). As the nuclear localization signal
      mutant IGFBP-3, which has a normal affinity to IGFs but binds other IGFBP-3
      partners poorly and fails to normally internalize, has reduced central activity
      on metabolism, we conclude that the effects of IGFBP-3 on the hypothalamus
      involve activity mediated by interfacing with other molecules in addition to
      IGFs. Marked, opposing, and independent physiological effects of IGF-I and IGFBP
      3 through central mechanisms may have implications on potential strategies in
      specific modulation of peripheral insulin action.

PMID- 17003345
TI  - Rosiglitazone treatment enhances acute AMP-activated protein kinase-mediated
      muscle and adipose tissue glucose uptake in high-fat-fed rats.
AB  - AMP-activated protein kinase (AMPK) has been implicated in the insulin
      sensitizing actions of thiazolidinediones (TZDs), but it is not known whether TZD
      treatment can enhance tissue glucose uptake in response to AMPK activation. The
      present study investigated the influence of the TZD rosiglitazone on glucose
      turnover induced by intravenous infusion of the AMPK activator 5-aminoimidazole 4
      carboxamide riboside (AICAR) under euglycemic and iso-insulinemic conditions in
      insulin-resistant high-fat-fed rats. We found that rosiglitazone treatment
      significantly enhanced AICAR-stimulated whole-body glucose disposal by 27% in
      high-fat-fed rats, and a 44% greater glucose infusion rate (both P < 0.01 vs.
      vehicle control rats) was required to maintain euglycemia. Along with this, both
      AICAR-stimulated glucose uptake and glucose incorporation into glycogen in muscle
      and adipose tissue were enhanced (P < 0.05). The enhanced glucose uptake and
      glycogen synthesis in muscle were associated with increased activity of total
      AMPK and the AMPKalpha2 subunit. In comparison, these effects were not apparent
      in rats fed standard rodent diet. Thus, our findings suggest that in addition to
      ameliorating insulin resistance, TZDs may enhance AMPK-stimulated glucose
      clearance into peripheral tissues in insulin-resistant states.

PMID- 17003346
TI  - Retinol-binding protein 4 in human obesity.
AB  - Studies in mice suggest that adipocytes serve as glucose sensors and regulate
      systemic glucose metabolism through release of serum retinol-binding protein 4
      (RBP4). This model has not been validated in humans. RBP4 was highly expressed in
      isolated mature human adipocytes and secreted by differentiating human
      adipocytes. In contrast to the animal data, RBP4 mRNA was downregulated in
      subcutaneous adipose tissue of obese women, and circulating RBP4 concentrations
      were similar in normal weight, overweight, and obese women (n = 74). RBP4 was
      positively correlated with GLUT4 expression in adipose tissue, independent of any
      obesity-associated variable. Five percent weight loss slightly decreased adipose
      RBP4 expression but did not influence circulating RBP4. In another set of
      experiments, we stratified patients (n = 14) by low or high basal fasting
      interstitial glucose concentrations, as determined by the microdialysis
      technique. Venous glucose concentrations were similar throughout oral glucose
      tolerance testing, and basal RBP4 expression in adipose tissue and serum RBP4
      concentrations were similar in the groups with higher and lower interstitial
      glucose levels. Our findings point to profound differences between rodents and
      humans in the regulation of adipose or circulating RBP4 and challenge the notion
      that glucose uptake by adipocytes has a dominant role in the regulation of RBP4.

PMID- 17003347
TI  - Lipin expression is attenuated in adipose tissue of insulin-resistant human
      subjects and increases with peroxisome proliferator-activated receptor gamma
      activation.
AB  - Lipin-alpha and -beta are the alternatively spliced gene products of the Lpin1
      gene, whose product lipin is required for adipocyte differentiation. Lipin
      deficiency causes lipodystrophy, fatty liver, and insulin resistance in mice,
      whereas adipose tissue lipin overexpression results in increased adiposity but
      improved insulin sensitivity. To assess lipin expression and its relation to
      insulin resistance in humans, we examined lipin-alpha and -beta mRNA levels in
      subjects with normal or impaired glucose tolerance. We found higher expression
      levels of both lipin isoforms in lean, insulin-sensitive subjects. When compared
      with normal glucose-tolerant subjects, individuals with impaired glucose
      tolerance were more insulin resistant, demonstrated higher levels of
      intramyocellular lipids (IMCLs), and expressed approximately 50% lower levels of
      lipin-alpha and -beta. In addition, there was a strong inverse correlation
      between adipose tissue lipin expression and muscle IMCLs but no evidence for an
      increase in muscle lipid oxidation. After treatment of the impaired glucose
      tolerant subjects with insulin sensitizers for 10 weeks, pioglitazone (but not
      metformin) resulted in a 60% increase in the insulin sensitivity index (Si) and a
      32% decrease in IMCLs (both P < 0.01), along with an increase in lipin-beta (but
      not lipin-alpha) expression by 200% (P < 0.005). Lipin expression in skeletal
      muscle, however, was not related to obesity or insulin resistance. Hence, high
      adipose tissue lipin expression is found in insulin-sensitive subjects, and lipin
      beta expression increases following treatment with pioglitazone. These results
      suggest that increased adipogenesis and/or lipogenesis in subcutaneous fat,
      mediated by the LPIN1 gene, may prevent lipotoxicity in muscle, leading to
      improved insulin sensitivity.

PMID- 17003348
TI  - Imaging docking and fusion of insulin granules induced by antidiabetes agents:
      sulfonylurea and glinide drugs preferentially mediate the fusion of newcomer, but
      not previously docked, insulin granules.
AB  - Sulfonylurea and glinide drugs, commonly used for antidiabetes therapies, are
      known to stimulate insulin release from pancreatic beta-cells by closing ATP
      sensitive K+ channels. However, the specific actions of these drugs on insulin
      granule motion are largely unknown. Here, we used total internal reflection
      fluorescence (TIRF) microscopy to analyze the docking and fusion of single
      insulin granules in live beta-cells exposed to either the sulfonylurea drug
      glibenclamide or the glinide drug mitiglinide. TIRF images showed that both
      agents caused rapid fusion of newcomer insulin granules with the cell membrane in
      both control and diabetic Goto-Kakizaki (GK) rat pancreatic beta-cells. However,
      in the context of beta-cells from sulfonylurea receptor 1 (SUR1) knockout mice,
      TIRF images showed that only mitiglinide, but not glibenclamide, caused fusion of
      newcomer insulin granules. Compositely, our data indicate that 1) the mechanism
      by which both sulfonylurea and glinide drugs promote insulin release entails the
      preferential fusion of newcomer, rather than previously docked, insulin granules,
      and that 2) mitiglinide can induce insulin release by a mechanism independent of
      mitiglinide binding to SUR1.

PMID- 17003349
TI  - C16:0 sulfatide inhibits insulin secretion in rat beta-cells by reducing the
      sensitivity of KATP channels to ATP inhibition.
AB  - Sulfatide (3'-sulfo-beta-galactosyl ceramide) is a glycosphingolipid present in
      mammalians in various fatty acid isoforms of which the saturated 16 carbon-atom
      length (C16:0) is more abundant in pancreatic islets than in neural tissue, where
      long-chain sulfatide isoforms dominate. We previously reported that sulfatide
      isolated from pig brain inhibits glucose-induced insulin secretion by activation
      of ATP-sensitive K+ channels (K(ATP) channels). Here, we show that C16:0
      sulfatide is the active isoform. It inhibits glucose-stimulated insulin secretion
      by reducing the sensitivity of the K(ATP) channels to ATP. (The half-maximal
      inhibitory concentration is 10.3 and 36.7 micromol/l in the absence and presence
      of C16:0 sulfatide, respectively.) C16:0 sulfatide increased whole-cell K(ATP)
      currents at intermediate glucose levels and reduced the ability of glucose to
      induce membrane depolarization, reduced electrical activity, and increased the
      cytoplasmic free Ca2+ concentration. Recordings of cell capacitance revealed that
      C16:0 sulfatide increased Ca2+-induced exocytosis by 215%. This correlated with a
      stimulation of insulin secretion by C16:0 sulfatide in intact rat islets exposed
      to diazoxide and high K+. C24:0 sulfatide or the sulfatide precursor, beta
      galactosyl ceramide, did not affect any of the measured parameters. C16:0
      sulfatide did not modulate glucagon secretion from intact rat islets. In betaTC3
      cells, sulfatide was expressed (mean [+/-SD] 0.30 +/- 0.04 pmol/microg protein),
      and C16:0 sulfatide was found to be the dominant isoform. No expression of
      sulfatide was detected in alphaTC1-9 cells. We conclude that a major mechanism by
      which the predominant sulfatide isoform in beta-cells, C16:0 sulfatide, inhibits
      glucose-induced insulin secretion is by reducing the K(ATP) channel sensitivity
      to the ATP block.

PMID- 17003350
TI  - Identification of insulin signaling elements in human beta-cells: autocrine
      regulation of insulin gene expression.
AB  - Although many studies using rodent islets and insulinoma cell lines have been
      performed to determine the role of insulin in the regulation of islet function,
      the autocrine effect of insulin on insulin gene expression is still
      controversial, and no consensus has yet been achieved. Because very little is
      known about the insulin signaling pathway in human islets, we used single-cell RT
      PCR to profile the expression of genes potentially involved in the insulin
      signaling cascade in human beta-cells. The detection of mRNAs for insulin
      receptor (IR)A and IRB; insulin receptor substrate (IRS)-1 and IRS-2;
      phosphoinositide 3-kinase (PI3K) catalytic subunits p110alpha, p110beta,
      PI3KC2alpha, and PI3KC2gamma; phosphoinositide-dependent protein kinase-1;
      protein kinase B (PKB)alpha, PKBbeta, and PKBgamma in the beta-cell population
      suggests the presence of a functional insulin signaling cascade in human beta
      cells. Small interfering RNA-induced reductions in IR expression in human islets
      completely suppressed glucose-stimulated insulin gene expression, suggesting that
      insulin regulates its own gene expression in human beta-cells. Defects in this
      regulation may accentuate the metabolic dysfunction associated with type 2
      diabetes.

PMID- 17003351
TI  - Immunoneutralization of endogenous glucagon reduces hepatic glucose output and
      improves long-term glycemic control in diabetic ob/ob mice.
AB  - In type 2 diabetes, glucagon levels are elevated in relation to the prevailing
      insulin and glucose levels. The relative hyperglucagonemia is linked to increased
      hepatic glucose output (HGO) and hyperglycemia. Antagonizing the effects of
      glucagon is therefore considered an attractive target for treatment of type 2
      diabetes. In the current study, effects of eliminating glucagon signaling with a
      glucagon monoclonal antibody (mAb) were investigated in the diabetic ob/ob mouse.
      Acute effects of inhibiting glucagon action were studied by an oral glucose
      tolerance test (OGTT) and by measurement of HGO. In addition, the effects of
      subchronic (5 and 14 days) glucagon mAb treatment on plasma glucose, insulin,
      triglycerides, and HbA1c (A1C) levels were investigated. Glucagon mAb treatment
      reduced the area under the curve for glucose after an OGTT, reduced HGO, and
      increased the rate of hepatic glycogen synthesis. Glucagon mAb treatment for 5
      days lowered plasma glucose and triglyceride levels, whereas 14 days of glucagon
      mAb treatment reduced A1C. In conclusion, acute and subchronic neutralization of
      endogenous glucagon improves glycemic control, thus supporting the contention
      that glucagon antagonism may represent a beneficial treatment of diabetes.

PMID- 17003352
TI  - Whole-body proteolysis rate is elevated in HIV-associated insulin resistance.
AB  - Type 2 diabetes is characterized by impaired glucose tolerance (IGT) and insulin
      resistance with respect to glucose metabolism but not amino acid metabolism. We
      examined whether whole-body leucine and protein metabolism are dysregulated in
      HIV-infected individuals with IGT. Glucose and leucine kinetics were measured
      under fasting insulin conditions and during euglycemic hyperinsulinemia using
      primed-constant infusions of 2H2-glucose and 13C-leucine in 10 HIV-seronegative
      control subjects, 16 HIV+ subjects with normal glucose tolerance, and 21 HIV+IGT
      subjects. Glucose disposal rate during hyperinsulinemia was lower in HIV+IGT than
      the other two groups. Absolute plasma leucine levels and rate of appearance
      (whole-body proteolysis) were higher in HIV+IGT at all insulin levels but
      declined in response to hyperinsulinemia in parallel to those in the other two
      groups. HIV+IGT had greater visceral adiposity, fasting serum interleukin (IL)-8
      and free fatty acid levels, and higher lipid oxidation rates during the clamp
      than the other two groups. These findings implicate several factors in the
      insulin signaling pathway, which may be further dysregulated in HIV+IGT, and
      support the notion that insulin signaling pathways for glucose and leucine
      metabolism may be disrupted by increased proinflammatory adipocytokines (IL-8)
      and increased lipid oxidation. Increased proteolysis may provide amino acids for
      gluconeogenesis, exacerbating hyperglycemia in HIV.

PMID- 17003353
TI  - Vitamin E and risk of type 2 diabetes in the women's health study randomized
      controlled trial.
AB  - We directly assessed the efficacy of vitamin E supplements for primary prevention
      of type 2 diabetes among apparently healthy women in the Women's Health Study
      randomized trial. Between 1992 and 2004, 38,716 apparently healthy U.S. women
      aged >or=45 years and free of diabetes, cancer, and cardiovascular disease were
      in two randomly assigned intervention groups and received 600 IU of vitamin E
      (alpha-tocopherol, n = 19,347) or placebo (n = 19,369) on alternate days. During
      a median 10-year follow-up, there were 827 cases of incident type 2 diabetes in
      the vitamin E group and 869 in the placebo group, a nonsignificant 5% risk
      reduction (relative risk [RR] 0.95 [95% CI 0.87-1.05], P = 0.31). There was no
      evidence that diabetes risk factors including age, BMI, postmenopausal hormone
      use, multivitamin use, physical activity, alcohol intake, and smoking status
      modified the effect of vitamin E on the risk of type 2 diabetes. In a sensitivity
      analysis taking compliance into account, women in the vitamin E group had an RR
      of 0.93 (95% CI 0.83-1.04) (P = 0.21) compared with those randomized to placebo.
      In this large trial with 10-year follow-up, alternate-day doses of 600 IU vitamin
      E provided no significant benefit for type 2 diabetes in initially healthy women.

PMID- 17003354
TI  - Insulin restores metabolic function in cultured cortical neurons subjected to
      oxidative stress.
AB  - We previously demonstrated that insulin has a neuroprotective role against
      oxidative stress, a deleterious condition associated with diabetes, ischemia, and
      age-related neurodegenerative diseases. In this study, we investigated the effect
      of insulin on neuronal glucose uptake and metabolism after oxidative stress in
      rat primary cortical neurons. On oxidative stress, insulin stimulates neuronal
      glucose uptake and subsequent metabolism into pyruvate, restoring intracellular
      ATP and phosphocreatine. Insulin also increases intracellular and decreases
      extracellular adenosine, counteracting the effect of oxidative stress. Insulin
      effects are apparently mediated by phosphatidylinositol 3-K and extracellular
      signal-regulated kinase signaling pathways. Extracellular adenosine under
      oxidative stress is largely inhibited after blockade of ecto-5'-nucleotidase,
      suggesting that extracellular adenosine results preferentially from ATP release
      and catabolism. Moreover, insulin appears to interfere with the ATP release
      induced by oxidative stress, regulating extracellular adenosine levels. In
      conclusion, insulin neuroprotection against oxidative stress-mediated damage
      involves 1) stimulation of glucose uptake and metabolism, increasing energy
      levels and intracellular adenosine and, ultimately, uric acid formation and 2) a
      decrease in extracellular adenosine, which may reduce the facilitatory activity
      of adenosine receptors.

PMID- 17003355
TI  - Serum visfatin increases with progressive beta-cell deterioration.
AB  - Visfatin has shown to be increased in type 2 diabetes but to be unrelated to
      insulin sensitivity. We hypothesized that visfatin is associated with insulin
      secretion in humans. To this aim, a cross-sectional study was conducted in 118
      nondiabetic men and 64 (35 men and 29 women) type 2 diabetic patients. Type 1
      diabetic patients with long-standing disease (n = 58; 31 men and 27 women) were
      also studied. In nondiabetic subjects, circulating visfatin (enzyme immunoassay)
      was independently associated with insulin secretion (acute insulin response to
      glucose [AIRg] from intravenous glucose tolerance tests) but not with insulin
      sensitivity (Si) or other metabolic or anthropometric parameters, and AIRg alone
      explained 8% of visfatin variance (beta = -0.29, P = 0.001). Circulating visfatin
      was increased in type 2 diabetes (mean 18 [95% CI 16-21] vs. 15 ng/ml [13-17] for
      type 2 diabetic and nondiabetic subjects, respectively; P = 0.017, adjusted for
      sex, age, and BMI), although this association was largely attenuated after
      accounting for HbA1c (A1C). Finally, circulating visfatin was found to be
      increased in patients with long-standing type 1 diabetes, even after adjusting
      for A1C values (37 ng/ml [34-40]; P < 0.0001, adjusted for sex, age, BMI, and A1C
      compared with either type 2 diabetic or nondiabetic subjects). In summary,
      circulating visfatin is increased with progressive beta-cell deterioration. The
      study of the regulation and role of visfatin in diabetes merits further
      consideration.

PMID- 17003356
TI  - Bardet-Biedl syndrome gene variants are associated with both childhood and adult
      common obesity in French Caucasians.
AB  - Bardet-Biedl syndrome (BBS) is a rare developmental disorder with the cardinal
      features of abdominal obesity, retinopathy, polydactyly, cognitive impairment,
      renal and cardiac anomalies, hypertension, and diabetes. BBS is genetically
      heterogeneous, with nine genes identified to date and evidence for additional
      loci. In this study, we performed mutation analysis of the coding and conserved
      regions of BBS1, BBS2, BBS4, and BBS6 in 48 French Caucasian individuals. Among
      the 36 variants identified, 12 were selected and genotyped in 1,943 French
      Caucasian case subjects and 1,299 French-Caucasian nonobese nondiabetic control
      subjects. Variants in BBS2, BBS4, and BBS6 showed evidence of association with
      common obesity in an age-dependent manner, the BBS2 single nucleotide
      polymorphism (SNP) being associated with common adult obesity (P = 0.0005) and
      the BBS4 and BBS6 SNPs being associated with common early-onset childhood obesity
      (P = 0.0003) and common adult morbid obesity (0.0003 < P < 0.007). The
      association of the BBS4 rs7178130 variant was found to be supported by
      transmission disequilibrium testing (P = 0.006). The BBS6 variants also showed
      nominal evidence of association with quantitative components of the metabolic
      syndrome (e.g., dyslipidemia, hyperglycemia), a complication previously described
      in BBS patients. In summary, our preliminary data suggest that variations at BBS
      genes are associated with risk of common obesity.

PMID- 17003357
TI  - A haplotype-based analysis of the PTPN22 locus in type 1 diabetes.
AB  - A recent addition to the list of widely confirmed type 1 diabetes risk loci is
      the PTPN22 gene encoding a lymphoid-specific phosphatase (Lyp). However, evidence
      supporting a role for PTPN22 in type 1 diabetes derives entirely from the study
      of just one coding single nucleotide polymorphism, 1858C/T. In the current study,
      the haplotype structure of the PTPN22 region was determined, and individual
      haplotypes were tested for association with type 1 diabetes in family-based
      tests. The 1858T risk allele occurred on only a single haplotype that was
      strongly associated with type 1 diabetes (P = 7.9 x 10(-5)). After controlling
      for the effects of this allele, two other haplotypes were observed to be weakly
      associated with type 1 diabetes (P < 0.05). Sequencing of the coding region of
      PTPN22 on these haplotypes revealed a novel variant (2250G/C) predicted to result
      in a nonsynonymous amino acid substitution. Analysis of PTPN22 transcripts from a
      subject heterozygous for this variant indicated that it interfered with normal
      mRNA splicing, resulting in a premature termination codon after exon 17. These
      results support the conclusion that the 1858C/T allele is the major risk variant
      for type 1 diabetes in the PTPN22 locus, but they suggest that additional
      infrequent coding variants at PTPN22 may also contribute to type 1 diabetes risk.

PMID- 17003358
TI  - Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with
      type 2 diabetes and reduce the insulin response to glucose in nondiabetic
      individuals.
AB  - Recently, common noncoding variants in the TCF7L2 gene were strongly associated
      with increased risk of type 2 diabetes in samples from Iceland, Denmark, and the
      U.S. We genotyped 13 single nucleotide polymorphisms (SNPs) across TCF7L2 in
      8,310 individuals in family-based and case-control designs from Scandinavia,
      Poland, and the U.S. We convincingly confirmed the previous association of TCF7L2
      SNPs with the risk of type 2 diabetes (rs7903146T odds ratio 1.40 [95% CI 1.30
      1.50], P = 6.74 x 10(-20)). In nondiabetic individuals, the risk genotypes were
      associated with a substantial reduction in the insulinogenic index derived from
      an oral glucose tolerance test (risk allele homozygotes have half the insulin
      response to glucose of noncarriers, P = 0.003) but not with increased insulin
      resistance. These results suggest that TCF7L2 variants may act through insulin
      secretion to increase the risk of type 2 diabetes.

PMID- 17003359
TI  - Common polymorphisms in the promoter of the visfatin gene (PBEF1) influence
      plasma insulin levels in a French-Canadian population.
AB  - The adipokine visfatin (PBEF1) exhibits insulin-mimetic effects and correlates
      strongly with visceral adiposity. We sequenced visfatin gene exons and 1,480 bp
      of the promoter in 23 individuals, including 18 individuals from the Quebec
      Family Study (QFS) with varying degrees of abdominal visceral fat, assessed by
      computed tomography, and 5 individuals from the Saguenay-Lac-Saint-Jean region of
      Quebec. We identified a synonymous polymorphism in exon 7 (SER301SER) but no
      nonsynonymous mutations. We observed an additional 10 polymorphisms, including 5
      intronic, 4 within the promoter, and 1 within the 3' untranslated region. Further
      promoter sequencing (816 bp) identified five additional single nucleotide
      polymorphisms (SNPs) in the QFS population. To investigate the role of visfatin
      gene variants in obesity-related phenotypes, we genotyped a total of 13 SNPs in
      the promoter region of the gene. From these, we analyzed the seven common SNPs in
      the QFS sample (918 participants from 208 families). A significant association
      was found between two SNPs (rs9770242 and rs1319501), in perfect linkage
      disequilibrium, and fasting insulin levels (P = 0.002). These SNPs were also
      associated with fasting glucose (P <or= 0.02). In addition, a more distal SNP
      (rs7789066) was significantly associated with the apolipoprotein B component of
      VLDL (P = 0.012).

PMID- 17003360
TI  - Transcription factor TCF7L2 genetic study in the French population: expression in
      human beta-cells and adipose tissue and strong association with type 2 diabetes.
AB  - Recently, the transcription factor 7-like 2 (TCF7L2) gene has been associated
      with type 2 diabetes in subjects of European origin in the DeCode study. We
      genotyped the two most associated variants (rs7903146 and rs12255372) in 2,367
      French type 2 diabetic subjects and in 2,499 control subjects. Both the T-allele
      of rs7903146 and the T-allele of rs12255372 significantly increase type 2
      diabetes risk with an allelic odds ratio (OR) of 1.69 (95% CI 1.55-1.83) (P = 6.0
      x 10(-35)) and 1.60 (1.47-1.74) (P = 7.6 x 10(-28)), respectively. In nonobese
      type 2 diabetic subjects (BMI <30 kg/m2, n = 1,346), the ORs increased to 1.89
      (1.72-2.09) (P = 2.1 x 10(-38)) and 1.79 (1.62-1.97) (P = 5.7 x 10(-31)),
      respectively. The rs7903146 T at-risk allele associates with decreased BMI and
      earlier age at diagnosis in the type 2 diabetic subjects (P = 8.0 x 10(-3) and P
      = 3.8 x 10(-4), respectively), which is supported by quantitative family-based
      association tests. TCF7L2 is expressed in most human tissues, including mature
      pancreatic beta-cells, with the exception of the skeletal muscle. In the
      subcutaneous and omental fat from obese type 2 diabetic subjects, TCF7L2
      expression significantly decreased compared with obese normoglycemic individuals.
      During rat fetal beta-cell differentiation, TCF7L2 expression pattern mimics the
      key marker NGN3 (neurogenin 3), suggesting a role in islet development. These
      data provide evidence that TCF7L2 is a major determinant of type 2 diabetes risk
      in European populations and suggests that this transcription factor plays a key
      role in glucose homeostasis.

PMID- 17003361
TI  - Role of a proline insertion in the insulin promoter factor 1 (IPF1) gene in
      African Americans with type 2 diabetes.
AB  - African Americans have twice the prevalence of type 2 diabetes as Caucasians and
      much greater genetic diversity. We identified an inframe insertion of a proline
      in the insulin promoter factor 1 (IPF1) gene (InsCCG243), which was relatively
      common (minor allele frequency approximately 0.08) in African Americans and
      showed a trend to association with type 2 diabetes in preliminary studies. An
      earlier French study identified InsCCG243 as a cause of autosomal dominant
      diabetes. To determine the role of this variant in African Americans, we examined
      an additional population from North Carolina (n = 368) and a subset of African
      American participants from the Atherosclerosis Risk in Communities (ARIC) study
      (n = 1,741). We also looked for segregation in 66 African-American families and
      for a role in insulin secretion in 112 nondiabetic subjects. InsCCG243 did not
      increase the risk of type 2 diabetes (P = 0.16 in North Carolina; P = 0.97 in the
      ARIC study) and did not segregate with type 2 diabetes in families. However, we
      found suggestive evidence for reduced insulin response to glucose (P = 0.05).
      Neither indirect measures of beta-cell mass nor beta-cell compensation were
      altered (P > 0.1). InsCCG243 does not act in a dominant, highly penetrant fashion
      in African Americans and is not a significant risk factor for type 2 diabetes in
      this population.

PMID- 17003362
TI  - IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual
      participants' data from 21 studies.
AB  - Several lines of evidence indicate a causal role of the cytokine interleukin (IL)
      6 in the development of type 2 diabetes in humans. Two common polymorphisms in
      the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C
      (rs1800796), have been investigated for association with type 2 diabetes in
      numerous studies but with results that have been largely equivocal. To clarify
      the relationship between the two IL6 variants and type 2 diabetes, we analyzed
      individual data on >20,000 participants from 21 published and unpublished
      studies. Collected data represent eight different countries, making this the
      largest association analysis for type 2 diabetes reported to date. The GC and CC
      genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes
      (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%.
      No evidence for association was found between IL6 -573G>C and type 2 diabetes.
      The observed association of the IL6 -174 C-allele with a reduced risk of type 2
      diabetes provides further evidence for the hypothesis that immune mediators are
      causally related to type 2 diabetes; however, because the association is
      borderline significant, additional data are still needed to confirm this finding.

PMID- 17003363
TI  - The alpha-adducin gene is associated with macrovascular complications and
      mortality in patients with type 2 diabetes.
AB  - We examined the association between alpha-adducin 1 (ADD1) gene polymorphism
      (Gly460Trp) with macrovascular complications and mortality in type 2 diabetes in
      a Caucasian population aged >or=55 years. The study was part of the Rotterdam
      Study, a prospective population-based cohort study. ADD1 polymorphism was
      determined in 6,471 participants, including 599 patients with type 2 diabetes at
      baseline. The prevalence of hypertension in type 2 diabetic patients was 2.57
      times higher in ADD1 TT carriers compared with GG carriers (95% CI 1.05-6.32, P =
      0.03). Homozygous T carriers also had a higher mean common carotid intima media
      thickness (IMT) compared with GG carriers (mean difference 0.05 mm, P for trend =
      0.03). In diabetic patients with hypertension, the risk of mortality was 1.83
      times higher in homozygous T carriers compared with the GG genotype group (95% CI
      1.07-3.16, P = 0.03). The increased risk was only present among TT carriers who
      did not use antidiabetes medication (hazard ratio 2.18 [95% CI 1.12-4.24], P =
      0.02). The results of this population-based cohort study suggest that the ADD1
      gene contributes to the risk of hypertension and increases mean common carotid
      IMT in patients with type 2 diabetes. Furthermore, the study indicates that the
      ADD1 polymorphism could be useful in identifying hypertensive type 2 diabetic
      patients with a high risk of mortality.

PMID- 17003364
TI  - Nonhematopoietic/endothelial SSEA-1+ cells define the most primitive progenitors
      in the adult murine bone marrow mesenchymal compartment.
AB  - It is believed that a primitive cell type that maintains the mesenchymal
      compartment exists in the bone marrow. However, this putative mesenchymal
      stem/progenitor cell is yet to be identified and isolated. We are reporting the
      identification, isolation, and detailed characterization of the most primitive
      mesenchymal progenitor cells in the adult murine bone marrow, based on the
      expression of stage-specific embryonic antigen-1 (SSEA-1). This primitive subset
      can be identified in mesenchymal cell cultures and also directly in the bone
      marrow, thus ascertaining for the first time their existence in an adult
      organism. Characterization of SSEA-1+ mesenchymal cells revealed that upon
      purification these cells gave rise to SSEA-1- mesenchymal cells, whereas the
      reverse could not be observed. Also, these SSEA-1+ cells have a much higher
      capacity to differentiate than their negative counterparts, not only to several
      mesenchymal cell types but also to unconventional cell types such as astrocyte-,
      endothelial-, and hepatocyte-like cells in vitro. Most importantly, a single-cell
      derived population was capable of differentiating abundantly into different
      mesenchymal cell types in vivo. Altogether we are proposing a hierarchical
      organization of the mesenchymal compartment, placing SSEA-1+ cells at the apex of
      this hierarchy.

PMID- 17003365
TI  - Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo.
AB  - Functional studies of embryonic epsilon-globin indicate that individuals with
      beta thalassemia or sickle cell disease are likely to benefit from therapeutic,
      transcriptional derepression of its encoding gene. The success of epsilon-globin
      gene-reactivation strategies, however, will be tempered by the stability that
      epsilon-globin mRNA exhibits in developmental stage-discordant definitive
      erythroid progenitors. Using cell culture and transgenic mouse model systems, we
      demonstrate that epsilon-globin mRNA is modestly unstable in immature,
      transcriptionally active erythroid cells, but that this characteristic has
      relatively little impact on the accumulation of epsilon-globin mRNA at subsequent
      stages of terminal differentiation. Importantly, the constitutive stability of
      epsilon-globin mRNA increases in transgenic mouse models of beta thalassemia,
      suggesting that epsilon- and beta-globin mRNAs are coregulated through a shared
      posttranscriptional mechanism. As anticipated, relevant cis-acting determinants
      of epsilon-globin mRNA stability map to its 3' UTR, consistent with the
      positioning of functionally related elements in other globin mRNAs. These studies
      demonstrate that posttranscriptional processes do not pose a significant
      practical barrier to epsilon-globin gene reactivation and, moreover, indicate
      that related therapeutic strategies may be particularly effective in individuals
      carrying beta-thalassemic gene defects.

PMID- 17003367
TI  - When is a mouse basophil not a basophil?
AB  - The identification and characterization of mouse basophils have historically been
      hampered by the extreme rarity of this cell type. Virtually no photomicrographs
      of hematologically stained (eg, Wright-Giemsa) examples of mouse basophils exist
      in the literature. However, 4 recent studies in the past 2 years have used flow
      cytometry and a defined set of cell-surface markers to identify and subsequently
      isolate mouse "basophils," including the publication of stained cytospin
      preparations of these cells. Surprisingly, a reevaluation of the data from all 4
      of the studies revealed several issues of concern that suggest that the cells
      under study are not necessarily basophils. Nonetheless, we propose that these
      studies do provide the foundation for a reevaluation of the defining
      characteristics of a basophil and/or provide support for the provocative
      conclusion that a new previously overlooked leukocyte subtype has been
      identified. The purpose of this commentary is to revisit these previously
      published studies, highlight the relevant issues, and provide a different
      perspective in the hope of developing a consensus within the research community
      as to the true identity of the "basophils" described in these studies.

PMID- 17003366
TI  - Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for
      children with acute lymphoblastic leukemia.
AB  - The Dana-Farber Cancer Institute (DFCI) Childhood ALL Consortium Protocol 95-01
      was designed to minimize therapy-related morbidity for children with newly
      diagnosed ALL without compromising efficacy. Patients participated in randomized
      comparisons of (1) doxorubicin given with or without dexrazoxane, a
      cardioprotectant (high-risk patients), (2) intensive intrathecal chemotherapy and
      cranial radiation (standard-risk patients), and (3) Erwinia and Escherichia coli
      asparaginase (all patients). Between 1996 and 2000, 491 patients (aged 0-18
      years) were enrolled (272 standard risk and 219 high risk). With a median of 5.7
      years of follow-up, the estimated 5-year event-free survival (EFS) for all
      patients was 82%+/-2%. Dexrazoxane did not have a significant impact on the 5
      year EFS of high-risk patients (P=.99), and there was no significant difference
      in outcome of standard-risk patients based on type of central nervous system
      (CNS) treatment (P=.26). Compared with E coli asparaginase, Erwinia asparaginase
      was associated with a lower incidence of toxicity (10% versus 24%), but also an
      inferior 5-year EFS (78%+/-4% versus 89%+/-3%, P=.01). We conclude that (1)
      dexrazoxane does not interfere with the antileukemic effect of doxorubicin, (2)
      intensive intrathecal chemotherapy is as effective as cranial radiation in
      preventing CNS relapse in standard-risk patients, and (3) once-weekly Erwinia is
      less toxic than E coli asparaginase, but also less efficacious.

PMID- 17003368
TI  - Characterization of a progenitor cell population in childhood T-cell acute
      lymphoblastic leukemia.
AB  - A significant proportion of children with T-cell acute lymphoblastic leukemia (T
      ALL) continue to fail therapy. Consequently, characterization of the cells that
      proliferate to maintain the disease should provide valuable information on the
      most relevant therapeutic targets. We have used in vitro suspension culture (SC)
      and nonobese diabetic-severe combined immune deficient (NOD/SCID) mouse assays to
      phenotypically characterize and purify T-ALL progenitor cells. Cells from 13
      pediatric cases were maintained in vitro for at least 4 weeks and expanded in 8
      cases. To characterize the progenitors, cells were sorted for expression of CD34
      and CD4 or CD7 and the subfractions were evaluated in vitro and in vivo. The
      majority of cells capable of long-term proliferation in vitro were derived from
      the CD34+/CD4- and CD34+/CD7- subfractions. Moreover, the CD34+/CD4- or CD7-
      cells were the only subfractions capable of NOD/SCID engraftment. These T-ALL
      cells successfully repopulated secondary and tertiary recipients with equivalent
      levels of engraftment, demonstrating self-renewal ability. The immunophenotype
      and genotype of the original leukemia cells were preserved with serial passage in
      the NOD/SCID mice. These data demonstrate the long-term repopulating ability of
      the CD34+/CD4- and CD34+/CD7- subfractions in T-ALL and suggest that a cell with
      a more primitive phenotype was the target for leukemic transformation in these
      cases.

PMID- 17003369
TI  - In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote
      experimental transplantation tolerance.
AB  - CD4+CD25+ regulatory T (Treg) cells play a critical role in the induction and
      maintenance of peripheral immune tolerance. In experimental transplantation
      models in which tolerance was induced, donor-specific Treg cells could be
      identified that were capable of transferring the tolerant state to naive animals.
      Furthermore, these cells appeared to have indirect allospecificity for donor
      antigens. Here we show that in vivo alloresponses can be regulated by donor
      alloantigen-specific Treg cells selected and expanded in vitro. Using autologous
      dendritic cells pulsed with an allopeptide from H2-Kb, we generated and expanded
      T-cell lines from purified Treg cells of CBA mice (H2k). Compared with fresh Treg
      cells, the cell lines maintained their characteristic phenotype, suppressive
      function, and homing capacities in vivo. When cotransferred with naive CD4+CD25-
      effector T cells after thymectomy and T-cell depletion in CBA mice that received
      CBK (H2k+Kb) skin grafts, the expanded Treg cells preferentially accumulated in
      the graft-draining lymph nodes and within the graft while preventing CBK but not
      third-party B10.A (H2k+Dd) skin graft rejection. In wild-type CBA, these donor
      specific Treg cells significantly delayed CBK skin graft rejection without any
      other immunosuppression. Taken together, these data suggest that in vitro
      generated tailored Treg cells could be considered a therapeutic tool to promote
      donor-specific transplant tolerance.

PMID- 17003370
TI  - STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90alpha
      and beta in multiple myeloma cells, which critically contribute to tumor-cell
      survival.
AB  - The combined blockade of the IL-6R/STAT3 and the MAPK signaling pathways has been
      shown to inhibit bone marrow microenvironment (BMM)-mediated survival of multiple
      myeloma (MM) cells. Here, we identify the molecular chaperones heat shock
      proteins (Hsp) 90alpha and beta as target genes of both pathways. The siRNA
      mediated knockdown of Hsp90 or treatment with the novel Hsp90 inhibitor 17-DMAG
      attenuated the levels of STAT3 and phospho-ERK and decreased the viability of MM
      cells. Although knockdown of Hsp90beta-unlike knockdown of Hsp90alpha-was
      sufficient to induce apoptosis, this effect was strongly increased when both
      Hsp90s were targeted, indicating a cooperation of both. Given the importance of
      the BMM for drug resistance and MM-cell survival, apoptosis induced by Hsp90
      inhibition was not mitigated in the presence of bone marrow stromal cells,
      osteoclasts, or endothelial cells. These observations suggest that a positive
      feedback loop consisting of Hsp90alpha/beta and major signaling pathways supports
      the survival of MM cells. Finally, in situ overexpression of both Hsp90 proteins
      was observed in most MMs but not in monoclonal gammopathy of undetermined
      significance (MGUS) or in normal plasma cells. Our results underpin a role for
      Hsp90alpha and beta in MM pathogenesis.

PMID- 17003371
TI  - Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts.
AB  - In contrast to lentiviral infections of humans and macaques, simian
      immunodeficiency virus (SIV) infection of natural hosts is nonpathogenic despite
      high levels of viral replication. However, the mechanisms underlying this absence
      of disease are unknown. Here we report that natural hosts for SIV infection
      express remarkably low levels of CCR5 on CD4+ T cells isolated from blood, lymph
      nodes, and mucosal tissues. Given that this immunologic feature is found in 5
      different species of natural SIV hosts (sooty mangabeys, African green monkeys,
      mandrills, sun-tailed monkeys, and chimpanzees) but is absent in 5
      nonnatural/recent hosts (humans, rhesus, pigtail, cynomolgus macaques, and
      baboons), it may represent a key feature of the coevolution between the virus and
      its natural hosts that led to a nonpathogenic infection. Beneficial effects of
      low CCR5 expression on CD4+ T cells may include the reduction of target cells for
      viral replication and a decreased homing of activated CD4+ T cells to inflamed
      tissue.

PMID- 17003372
TI  - ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other
      agonists.
AB  - Interaction between von Willebrand factor (VWF) and platelet GP Ib-IX-V is
      required for hemostasis, in part because intracellular signals from VWF/GP Ib-IX
      V activate the ligand-binding function of integrin alphaIIbbeta3. Because they
      also induce tyrosine phosphorylation of the ADAP adapter, we investigated ADAP's
      role in GP Ib-IX-V signal transduction. Fibrinogen or ligand-mimetic POW-2 Fab
      binding to alphaIIbbeta3 was stimulated by adhesion of ADAP+/+ murine platelets
      to dimeric VWF A1A2 but was significantly reduced in ADAP-/- platelets (P<.01).
      alphaIIbbeta3 activation by ADP or a Par4 thrombin receptor agonist was also
      decreased in ADAP-/- platelets. ADAP stabilized the expression of another
      adapter, SKAP-HOM, via interaction with the latter's SH3 domain. However, no
      abnormalities in alphaIIbbeta3 activation were observed in SKAP-HOM-/- platelets,
      which express normal ADAP levels, further implicating ADAP as a modulator of
      alphaIIbbeta3 function. Under shear flow conditions over a combined surface of
      VWF A1A2 and fibronectin to test interactions involving GP Ib-IX-V and
      alphaIIbbeta3, respectively, ADAP-/- platelets displayed reduced alphaIIbbeta3
      dependent stable adhesion. Furthermore, ADAP-/- mice demonstrated increased
      rebleeding from tail wounds. These studies establish ADAP as a component of
      inside-out signaling pathways that couple GP Ib-IX-V and other platelet agonist
      receptors to alphaIIbbeta3 activation.

PMID- 17003373
TI  - Flavopiridol administered using a pharmacologically derived schedule is
      associated with marked clinical efficacy in refractory, genetically high-risk
      chronic lymphocytic leukemia.
AB  - Despite promising preclinical studies with the cyclin-dependent kinase inhibitor
      flavopiridol in chronic lymphocytic leukemia (CLL) and other diseases, previous
      clinical trials with this agent have been disappointing. The discovery of
      differential protein binding of flavopiridol in human and bovine serum
      contributed to an effective pharmacokinetic-derived schedule of administration of
      this agent. On the basis of pharmacokinetic modeling using our in vitro results
      and data from a previous trial, we initiated a phase 1 study using a 30-minute
      loading dose followed by 4 hours of infusion administered weekly for 4 of 6 weeks
      in patients with refractory CLL. A group of 42 patients were enrolled on 3
      cohorts (cohort 1, 30 mg/m2 loading dose followed by 30 mg/m2 4-hour infusion;
      cohort 2, 40 mg/m2 loading dose followed by 40 mg/m2 4-hour infusion; and cohort
      3, cohort 1 dose for treatments 1 to 4, then a 30 mg/m2 loading dose followed by
      a 50 mg/m2 4-hour infusion). The dose-limiting toxicity using this novel schedule
      was hyperacute tumor lysis syndrome. Aggressive prophylaxis and exclusion of
      patients with leukocyte counts greater than 200x10(9)/L have made this drug safe
      to administer at the cohort 3 dose. Of the 42 patients treated, 19 (45%) achieved
      a partial response with a median response duration that exceeds 12 months.
      Responses were noted in patients with genetically high-risk disease, including 5
      (42%) of 12 patients with del(17p13.1) and 13 (72%) of 18 patients with
      del(11q22.3). Flavopiridol administered using this novel schedule has significant
      clinical activity in refractory CLL. Patients with bulky disease and high-risk
      genetic features have achieved durable responses, thereby justifying further
      study of flavopiridol in CLL and other diseases.

PMID- 17003375
TI  - Edelfosine and perifosine induce selective apoptosis in multiple myeloma by
      recruitment of death receptors and downstream signaling molecules into lipid
      rafts.
AB  - Multiple myeloma (MM) is an incurable B-cell malignancy, requiring new
      therapeutic strategies. We have found that synthetic alkyl-lysophospholipids
      (ALPs) edelfosine and perifosine induced apoptosis in MM cell lines and patient
      MM cells, whereas normal B and T lymphocytes were spared. ALPs induced
      recruitment of Fas/CD95 death receptor, Fas-associated death domain-containing
      protein, and procaspase-8 into lipid rafts, leading to the formation of the death
      inducing signaling complex (DISC) and apoptosis. TNF-related apoptosis-inducing
      ligand receptor-1/death receptor 4 (TRAIL-R1/DR4) and TRAIL-R2/DR5, as well as
      Bid, were also recruited into lipid rafts, linking death receptor and
      mitochondrial signaling pathways. ALPs induced mitochondrial cytochrome c
      release. Bcl-X(L) overexpression prevented cytochrome c release and apoptosis. A
      Fas/CD95-deficient MM subline expressing DR4 and DR5 was resistant to edelfosine.
      Fas/CD95 retrovirus transduction bestowed edelfosine sensitivity in these cells.
      A Fas/CD95 mutant lacking part of the intracellular domain was ineffective. Lipid
      raft disruption prevented ALP-induced Fas/CD95 clustering, DISC formation, and
      apoptosis. ALP-induced apoptosis was Fas/CD95 ligand (FasL/CD95L) independent.
      ALP-induced recruitment of death receptors in lipid rafts potentiated MM cell
      killing by FasL/CD95L and TRAIL. These data uncover a novel lipid raft-mediated
      therapy in MM involving concentration of death receptors in membrane rafts, with
      Fas/CD95 playing a major role in ALP-mediated apoptosis.

PMID- 17003376
TI  - Increased plasma transferrin, altered body iron distribution, and microcytic
      hypochromic anemia in ferrochelatase-deficient mice.
AB  - Patients with deficiency in ferrochelatase (FECH), the last enzyme of the heme
      biosynthetic pathway, experience a painful type of skin photosensitivity called
      erythropoietic protoporphyria (EPP), which is caused by the excessive production
      of protoporphyrin IX (PPIX) by erythrocytes. Controversial results have been
      reported regarding hematologic status and iron status of patients with EPP. We
      thoroughly explored these parameters in Fechm1Pas mutant mice of 3 different
      genetic backgrounds. FECH deficiency induced microcytic hypochromic anemia
      without ringed sideroblasts, little or no hemolysis, and no erythroid
      hyperplasia. Serum iron, ferritin, hepcidin mRNA, and Dcytb levels were normal.
      The homozygous Fechm1Pas mutant involved no tissue iron deficiency but showed a
      clear-cut redistribution of iron stores from peripheral tissues to the spleen,
      with a concomitant 2- to 3-fold increase in transferrin expression at the mRNA
      and the protein levels. Erythrocyte PPIX levels strongly correlated with serum
      transferrin levels. At all stages of differentiation in our study, transferrin
      receptor expression in bone marrow erythroid cells in Fech(m1Pas) was normal in
      mutant mice but not in patients with iron-deficiency anemia. Based on these
      observations, we suggest that oral iron therapy is not the therapy of choice for
      patients with EPP and that the PPIX-liver transferrin pathway plays a role in the
      orchestration of iron distribution between peripheral iron stores, the spleen,
      and the bone marrow.

PMID- 17003374
TI  - SHP-2 phosphatase is required for hematopoietic cell transformation by Bcr-Abl.
AB  - SHP-2 phosphatase forms a stable protein complex with and is heavily tyrosine
      phosphorylated by the oncogenic tyrosine kinase Bcr-Abl. However, the role of SHP
      2 in Bcr-Abl-mediated leukemogenesis is unclear. In the present report, we
      provide evidence that SHP-2 is required for hematopoietic cell transformation by
      Bcr-Abl. In vitro biological effects of Bcr-Abl transduction were diminished in
      SHP-2Delta/Delta hematopoietic cells, and the leukemic potential of Bcr-Abl
      transduced SHP-2Delta/Delta cells in recipient animals was compromised. Further
      analyses showed that Bcr-Abl protein (p210) was degraded, and its oncogenic
      signaling was greatly decreased in SHP-2Delta/Delta cells. Treatment with
      proteasome inhibitors or reintroduction of SHP-2 restored p210 level in Bcr-Abl
      transduced SHP-2Delta/Delta cells. Subsequent investigation revealed that SHP-2
      interacted with heat shock protein 90, an important chaperone protein protecting
      p210 from proteasome-mediated degradation. The role of SHP-2 in the stability of
      p210 is independent of its catalytic activity. Blockade of SHP-2 expression in
      p210-expressing cells by antisense or small-interfering RNA approaches decreased
      p210 level, causing cell death. Inhibition of SHP-2 enzymatic activity by
      overexpression of catalytically inactive SHP-2 mutant did not destabilize p210
      but enhanced serum starvation-induced apoptosis, suggesting that SHP-2 also plays
      an important role in downstream signaling of p210 kinase. These studies
      identified a novel function of SHP-2 and suggest that SHP-2 might be a useful
      target for controlling Bcr-Abl-positive leukemias.

PMID- 17003377
TI  - B-cell receptor signaling in chronic lymphocytic leukemia cells is regulated by
      overexpressed active protein kinase CbetaII.
AB  - Signals through the B-cell antigen receptor (BCR) are important for the survival
      of chronic lymphocytic leukemia (CLL) cells. Therefore, factors that influence
      these signals have important pathophysiological roles in this disease. One key
      mediator of BCR signaling is protein kinase C beta (PKCbeta), which regulates the
      activation of I-kappaB kinases and the deactivation of Bruton tyrosine kinase
      within the signaling pathways initiated by BCR engagement. The present study
      demonstrates that overexpression of the PKCbetaII isoform is a feature of CLL
      cells and that activity of this enzyme strongly correlates with CLL cell response
      to BCR engagement. Thus, intracellular Ca2+ release and increases in cell
      survival after BCR cross-linking were significantly greater in CLL patients with
      low levels than in CLL patients with high levels of active PKCbetaII.
      Furthermore, BCR-induced Ca2+ fluxes could be restored in CLL patients with high
      levels of active PKCbetaII by pretreating the cells with the PKCbeta-specific
      inhibitor LY379196. Conversely, BCR-mediated intracellular Ca2+ release could be
      inhibited in CLL cells with low levels of active PKCbetaII by pretreatment with
      the PKC agonist bryostatin. Taken together, these results demonstrate that
      overexpressed active PKCbetaII plays a role in the regulation and outcome of BCR
      signals that can be important for the progression of CLL.

PMID- 17003378
TI  - The THAP-zinc finger protein THAP1 regulates endothelial cell proliferation
      through modulation of pRB/E2F cell-cycle target genes.
AB  - We recently cloned a novel human nuclear factor (designated THAP1) from
      postcapillary venule endothelial cells (ECs) that contains a DNA-binding THAP
      domain, shared with zebrafish E2F6 and several Caenorhabditis elegans proteins
      interacting genetically with retinoblastoma gene product (pRB). Here, we show
      that THAP1 is a physiologic regulator of EC proliferation and cell-cycle
      progression, 2 essential processes for angiogenesis. Retroviral-mediated gene
      transfer of THAP1 into primary human ECs inhibited proliferation, and large-scale
      expression profiling with microarrays revealed that THAP1-mediated growth
      inhibition is due to coordinated repression of pRB/E2F cell-cycle target genes.
      Silencing of endogenous THAP1 through RNA interference similarly inhibited EC
      proliferation and G1/S cell-cycle progression, and resulted in down-regulation of
      several pRB/E2F cell-cycle target genes, including RRM1, a gene required for S
      phase DNA synthesis. Chromatin immunoprecipitation assays in proliferating ECs
      showed that endogenous THAP1 associates in vivo with a consensus THAP1-binding
      site found in the RRM1 promoter, indicating that RRM1 is a direct transcriptional
      target of THAP1. The similar phenotypes observed after THAP1 overexpression and
      silencing suggest that an optimal range of THAP1 expression is essential for EC
      proliferation. Together, these data provide the first links in mammals among THAP
      proteins, cell proliferation, and pRB/E2F cell-cycle pathways.

PMID- 17003379
TI  - Eosinophils are a major intravascular location for tissue factor storage and
      exposure.
AB  - Blood cell progenitors were scanned for the presence of the coagulation starter
      protein tissue factor (TF) by immunoelectron microscopy. Thereby, substantial TF
      expression was observed in the precursor cells of eosinophils. TF levels were
      lower in basophil precursors and barely detectable in neutrophil progenitors. In
      peripheral blood immediately processed to avoid activation of the TF gene, mature
      eosinophils were found to considerably express TF, unique among the granulocyte
      and monocyte fractions. TF was preferentially located in the specific granules in
      resting eosinophils. Platelet-activating factor (PAF), and more pronounced,
      granulocyte-macrophage colony-stimulating factor (GM-CSF) plus PAF, caused
      translocation of preformed TF to the eosinophil cell membrane. GM-CSF/PAF also
      increased the TF transcript levels. The activated eosinophils exhibited
      procoagulant activity that was abrogated by TF inhibition. Targeting the
      extracellular domain of TF with specific antibodies markedly suppressed the
      initial phase of the eosinophil passage across the IL-4-activated endothelium.
      Eosinophil rolling and firm adhesion remained unaffected. This suggests that TF
      specifically facilitates the early transendothelial migration of the eosinophils.
      In summary, eosinophils maintain a high TF expression during maturation,
      providing a main source of preformed TF in blood, which might be relevant for the
      thrombogenesis promoted by hypereosinophilic conditions.

PMID- 17003381
TI  - Active MAC-1 (CD11b/CD18) on DCs inhibits full T-cell activation.
AB  - The beta2 integrins are important for transendothelial migration of leukocytes as
      well as for T-cell activation during antigen presentation. Despite abundant
      expression of beta2 integrins on antigen-presenting cells (APCs), their
      functional relevance for antigen presentation is completely unclear. We show here
      that dendritic cells (DCs) from CD18-deficient mice, which lack all functional
      beta2 integrins, have no defect in antigen presentation. Moreover, DCs from
      normal mice express inactive beta2 integrins that do not become activated on
      contact with T cells, at least in vitro. Pharmacologic activation of beta2
      integrins on DCs results in a significant reduction of their T cell-activating
      capacity. This effect is mediated by Mac-1 (CD11b/CD18) on DCs because it could
      be reversed via blocking antibodies against CD18 and CD11b. Furthermore, the
      antigen-presenting capacity of macrophages, which express constitutively active
      beta2 integrins, is significantly enhanced on Mac-1 blockade. We therefore
      conclude that active CD11b/CD18 (Mac-1) on APCs directly inhibits T-cell
      activation.

PMID- 17003382
TI  - Early FDG-PET assessment in combination with clinical risk scores determines
      prognosis in recurring lymphoma.
AB  - This study was set up to demonstrate whether prognostic classification based on
      the secondary age-adjusted International Prognostic Index (sAA-IPI) for recurring
      aggressive non-Hodgkin lymphoma (NHL) or the prognostic score for recurring
      Hodgkin lymphoma (HL) can be improved by including the midtreatment results of
      fluorine-18-fluorodeoxy-glucose-positron emission tomography (FDG-PET). Clinical
      data on patients with recurring lymphoma who were treated with second-line
      chemotherapy (DHAP-VIM-DHAP) followed by autologous stem cell transplantation
      (ASCT) were collected and combined with the results of FDG-PET performed before
      and after 2 cycles of reinduction chemotherapy. PET responses after 2 courses
      were scored as complete remission (CR), partial remission (PR), or no response
      (NR). A multivariate analysis was performed to design a predictive model. The
      number of patients (101 of 117) included those (78 patients with aggressive NHL
      and 23 patients with HL) that could be analyzed according to protocol. Of these,
      80 patients were chemosensitive and 77 received transplants. Both secondary
      clinical risk score (P<.001) and FDG-PET response (P<.001) were independent
      predictive factors for the total evaluable group of patients with lymphoma and
      for patients with NHL alone. The combined use of the clinical risk score and FDG
      PET response after 2 chemotherapy courses identified at least 4 categories of
      patients with a failure-free survival varying between 5% to 100% after
      transplantation (P<.001). These data indicate that the secondary clinical risk
      score in conjunction with FDG-PET response provides a more accurate prognostic
      instrument for the outcome of second-line treatment at least in patients with
      recurring NHL.

PMID- 17003380
TI  - Risk- and response-based classification of childhood B-precursor acute
      lymphoblastic leukemia: a combined analysis of prognostic markers from the
      Pediatric Oncology Group (POG) and Children's Cancer Group (CCG).
AB  - The Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) joined
      to form the Children's Oncology Group (COG) in 2000. This merger allowed analysis
      of clinical, biologic, and early response data predictive of event-free survival
      (EFS) in acute lymphoblastic leukemia (ALL) to develop a new classification
      system and treatment algorithm. From 11 779 children (age, 1 to 21.99 years) with
      newly diagnosed B-precursor ALL consecutively enrolled by the CCG (December 1988
      to August 1995, n=4986) and POG (January 1986 to November 1999, n=6793), we
      retrospectively analyzed 6238 patients (CCG, 1182; POG, 5056) with informative
      cytogenetic data. Four risk groups were defined as very high risk (VHR; 5-year
      EFS, 45% or below), lower risk (5-year EFS, at least 85%), and standard and high
      risk (those remaining in the respective National Cancer Institute [NCI] risk
      groups). VHR criteria included extreme hypodiploidy (fewer than 44 chromosomes),
      t(9;22) and/or BCR/ABL, and induction failure. Lower-risk patients were NCI
      standard risk with either t(12;21) (TEL/AML1) or simultaneous trisomies of
      chromosomes 4, 10, and 17. Even with treatment differences, there was high
      concordance between the CCG and POG analyses. The COG risk classification scheme
      is being used for division of B-precursor ALL into lower- (27%), standard- (32%),
      high- (37%), and very-high- (4%) risk groups based on age, white blood cell (WBC)
      count, cytogenetics, day-14 marrow response, and end induction minimal residual
      disease (MRD) by flow cytometry in COG trials.

PMID- 17003383
TI  - The cover. The Lamp.

PMID- 17003384
TI  - A piece of my mind. Raising a woman.

PMID- 17003385
TI  - Lasker honors cell biologists, psychiatrist.

PMID- 17003386
TI  - Researchers draft guidelines for clinical use of pharmacogenomics.

PMID- 17003387
TI  - Tight blood glucose control pays off in reduced cardiovascular risk in diabetes.

PMID- 17003388
TI  - MIT, FDA develop safety monitoring tool.

PMID- 17003389
TI  - Neurotoxicity of mercury in dental amalgam.

PMID- 17003390
TI  - Risks of dental amalgam in children.

PMID- 17003391
TI  - Neurotoxicity of mercury in dental amalgam.

PMID- 17003392
TI  - Clinical trials in hypertension.

PMID- 17003393
TI  - Clinical trials in hypertension.

PMID- 17003394
TI  - Risk of death associated with nesiritide in patients with acutely decompensated
      heart failure.

PMID- 17003395
TI  - Prediction of MLH1 and MSH2 mutations in Lynch syndrome.
AB  - CONTEXT: Lynch syndrome is caused primarily by mutations in the mismatch repair
      genes MLH1 and MSH2. OBJECTIVES: To analyze MLH1/MSH2 mutation prevalence in a
      large cohort of patients undergoing genetic testing and to develop a clinical
      model to predict the likelihood of finding a mutation in at-risk patients.
      DESIGN, SETTING, AND PARTICIPANTS: Personal and family history were obtained for
      1914 unrelated probands who submitted blood samples starting in the year 2000 for
      full gene sequencing of MLH1/MSH2. Genetic analysis was performed using a
      combination of sequence analysis and Southern blotting. A multivariable model was
      developed using logistic regression in an initial cohort of 898 individuals and
      subsequently prospectively validated in 1016 patients. The complex model that we
      have named PREMM(1,2) (Prediction of Mutations in MLH1 and MSH2) was developed
      into a Web-based tool that incorporates personal and family history of cancer and
      adenomas. MAIN OUTCOME MEASURE: Deleterious mutations in MLH1/MSH2 genes.
      RESULTS: Overall, 14.5% of the probands (130/898) carried a pathogenic mutation
      (MLH1, 6.5%; MSH2, 8.0%) in the development cohort and 15.3% (155/1016) in the
      validation cohort, with 42 (27%) of the latter being large rearrangements. Strong
      predictors of mutations included proband characteristics (presence of colorectal
      cancer, especially > or =2 separate diagnoses, or endometrial cancer) and family
      history (especially the number of first-degree relatives with colorectal or
      endometrial cancer). Age at diagnosis was particularly important for colorectal
      cancer. The multivariable model discriminated well at external validation, with
      an area under the receiver operating characteristic curve of 0.80 (95% confidence
      interval, 0.76-0.84). CONCLUSIONS: Personal and family history characteristics
      can accurately predict the outcome of genetic testing in a large population at
      risk of Lynch syndrome. The PREMM(1,2) model provides clinicians with an
      objective, easy-to-use tool to estimate the likelihood of finding mutations in
      the MLH1/MSH2 genes and may guide the strategy for molecular evaluation.

PMID- 17003396
TI  - Prediction of germline mutations and cancer risk in the Lynch syndrome.
AB  - CONTEXT: Identifying families at high risk for the Lynch syndrome (ie, hereditary
      nonpolyposis colorectal cancer) is critical for both genetic counseling and
      cancer prevention. Current clinical guidelines are effective but limited by
      applicability and cost. OBJECTIVE: To develop and validate a genetic counseling
      and risk prediction tool that estimates the probability of carrying a deleterious
      mutation in mismatch repair genes MLH1, MSH2, or MSH6 and the probability of
      developing colorectal or endometrial cancer. DESIGN, SETTING, AND PATIENTS:
      External validation of the MMRpro model was conducted on 279 individuals from 226
      clinic-based families in the United States, Canada, and Australia (referred
      between 1993-2005) by comparing model predictions with results of highly
      sensitive germline mutation detection techniques. MMRpro models the autosomal
      dominant inheritance of mismatch repair mutations, with parameters based on meta
      analyses of the penetrance and prevalence of mutations and of the predictive
      values of tumor characteristics. The model's prediction is tailored to each
      individual's detailed family history information on colorectal and endometrial
      cancer and to tumor characteristics including microsatellite instability. MAIN
      OUTCOME MEASURE: Ability of MMRpro to correctly predict mutation carrier status,
      as measured by operating characteristics, calibration, and overall accuracy.
      RESULTS: In the independent validation, MMRpro provided a concordance index of
      0.83 (95% confidence interval, 0.78-0.88) and a ratio of observed to predicted
      cases of 0.94 (95% confidence interval, 0.84-1.05). This results in higher
      accuracy than existing alternatives and current clinical guidelines. CONCLUSIONS:
      MMRpro is a broadly applicable, accurate prediction model that can contribute to
      current screening and genetic counseling practices in a high-risk population. It
      is more sensitive and more specific than existing clinical guidelines for
      identifying individuals who may benefit from MMR germline testing. It is
      applicable to individuals for whom tumor samples are not available and to
      individuals in whom germline testing finds no mutation.

PMID- 17003397
TI  - Impact of annual targeted treatment on infectious trachoma and susceptibility to
      reinfection.
AB  - CONTEXT: The World Health Organization developed the SAFE strategy (Surgery for
      trichiasis; Antibiotics for Chlamydia trachomatis infection; Facial cleanliness;
      and Environmental improvement) to eliminate blinding trachoma globally by the
      year 2020. Despite a number of studies using various intervals of treatment for
      different prevalence rates, there has been a lack of sufficient follow-up beyond
      the final treatment point to determine rates of recurrence of disease and
      infection and the risk factors that may contribute to each. OBJECTIVE: To
      evaluate the impact of 2 annual targeted azithromycin treatments on active
      trachoma and C trachomatis infection rates over 3 years in Vietnam. DESIGN,
      SETTING, AND PARTICIPANTS: Three communes were randomly selected for a
      longitudinal study in Vietnam from November 2000 through November 2003.
      Individuals (n = 3186) were graded for trachoma followed by conjunctival sampling
      to detect chlamydiae by commercial polymerase chain reaction. Grading and
      chlamydial detection were repeated every 6 months for 3 years. INTERVENTION:
      Azithromycin was given to children aged 5 through 15 years with active trachoma
      and their household members in SAFE and SA communes at baseline and 12 months;
      these communes were compared with the S-only control commune that did not receive
      azithromycin targeted treatment. MAIN OUTCOME MEASURES: Prevalence and incidence
      of active trachoma and C trachomatis infection in all communes at baseline, 6,
      12, 18, 24, and 36 months. Subgroup analysis evaluated new infection, continuing
      infection, and reinfection at 6, 12, 18, 24, and 36 months and risk factors for
      each. RESULTS: Reinfection rates increased significantly between 12 and 36 months
      for SAFE (from 1.6 to 29.3 per 1000; P<.001) and SA (5.1 to 25.3 per 1000; P =
      .002) communes but not for the S-only commune (13.4 to 6.7 per 1000; P = .55)
      after 24 months. Compared with the S-only commune, mixed-effects and generalized
      estimating equations (GEE) logistic models showed that reinfection risk was
      significantly higher for SAFE (odds ratio [OR], 4.1; 95% confidence interval
      [CI], 1.5-9.8; P = .005) and SA (OR, 4.2; 95% CI, 1.1-17.3; P = .04) communes at
      36 months. CONCLUSIONS: Increasing reinfection rates suggest that treatment may
      interrupt the duration of infection required for developing immunity, increasing
      the number of individuals susceptible to reinfection and adversely affecting
      disease prevalence over time. Additional research is needed to determine optimal
      trachoma control strategies, including evaluation of the "F" and "E" components.
      TRIAL REGISTRATION: www.actr.org.au Identifier: 12606000360516.

PMID- 17003398
TI  - Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in
      untreated HIV infection.
AB  - CONTEXT: Plasma human immunodeficiency virus (HIV) RNA level predicts HIV disease
      progression, but the extent to which it explains the variability in rate of CD4
      cell depletion is poorly characterized. OBJECTIVE: To estimate the proportion of
      variability in rate of CD4 cell loss predicted by presenting plasma HIV RNA
      levels in untreated HIV-infected persons. DESIGN: Repeated-measures analyses of 2
      multicenter cohorts, comprising observations beginning on May 12, 1984, and
      ending on August 26, 2004. Analyses were conducted between August 2004 and March
      2006. SETTING: Two cohorts of HIV-infected persons: patients followed up at 4 US
      teaching medical institutions or participating in either the Research in Access
      to Care for the Homeless Cohort (REACH) or the San Francisco Men's Health Study
      (SFMHS) cohorts and participants in the Multicenter AIDS Cohort Study (MACS)
      cohort. PARTICIPANTS: Antiretroviral treatment-naive, chronically HIV-infected
      persons (n = 1289 and n = 1512 for each of the 2 cohorts) untreated during the
      observation period (> or =6 months) and with at least 1 HIV RNA level and 2 CD4
      cell counts available. Approximately 35% were nonwhite, and 35% had risk factors
      other than male-to-male sexual contact. MAIN OUTCOME MEASURES: The extent to
      which presenting plasma HIV RNA level could explain the rate of model-derived
      yearly CD4 cell loss, as estimated by the coefficient of determination (R2).
      RESULTS: In both cohorts, higher presenting HIV RNA levels were associated with
      greater subsequent CD4 cell decline. In the study cohort, median model-estimated
      CD4 cell decrease among participants with HIV RNA levels of 500 or less, 501 to
      2000, 2001 to 10,000, 10,001 to 40,000, and more than 40,000 copies/mL were 20,
      39, 48, 56, and 78 cells/microL, respectively. Despite this trend across broad
      categories of HIV RNA levels, only a small proportion of CD4 cell loss
      variability (4%-6%) could be explained by presenting plasma HIV RNA level.
      Analyses using multiple HIV RNA measurements or restricting to participants with
      high HIV RNA levels improved this correlation minimally (R2, 0.09), and
      measurement error was estimated to attenuate these associations only marginally
      (deattenuated R2 in the 2 cohorts, 0.05 and 0.08, respectively). CONCLUSIONS:
      Presenting HIV RNA level predicts the rate of CD4 cell decline only minimally in
      untreated persons. Other factors, as yet undefined, likely drive CD4 cell losses
      in HIV infection. These findings have implications for treatment decisions in HIV
      infection and for understanding the pathogenesis of progressive immune
      deficiency.

PMID- 17003399
TI  - Recommendations for the care of individuals with an inherited predisposition to
      Lynch syndrome: a systematic review.
AB  - CONTEXT: About 2% of all colorectal cancer occurs in the context of the autosomal
      dominantly inherited Lynch syndrome, which is due to mutations in mismatch repair
      genes. Potential risk-reducing interventions are recommended for individuals
      known to have these mutations. OBJECTIVES: To review cancer risks and data on
      screening efficacy in the context of Lynch syndrome (hereditary nonpolyposis
      colorectal cancer) and to provide recommendations for clinical management for
      affected families, based on available evidence and expert opinion. DATA SOURCES
      AND STUDY SELECTION: A systematic literature search using PubMed and the Cochrane
      Database of Systematic Reviews, reference list review of retrieved articles,
      manual searches of relevant articles, and direct communication with other
      researchers in the field. Search terms included hereditary non-polyposis colon
      cancer, Lynch syndrome, microsatellite instability, mismatch repair genes, and
      terms related to the biology of Lynch syndrome. Only peer-reviewed, full-text,
      English-language articles concerning human subjects published between January 1,
      1996, and February 2006 were included. The US Preventive Services Task Force's 2
      tier system was adapted to describe the quality of evidence and to assign
      strength to the recommendations for each guideline. EVIDENCE SYNTHESIS: The
      evidence supports colonoscopic surveillance for individuals with Lynch syndrome,
      although the optimal age at initiation and frequency of examinations is
      unresolved. Colonoscopy is recommended every 1 to 2 years starting at ages 20 to
      25 years (age 30 years for those with MSH6 mutations), or 10 years younger than
      the youngest age of the person diagnosed in the family. While fully acknowledging
      absence of demonstrated efficacy, the following are also recommended annually:
      endometrial sampling and transvaginal ultrasound of the uterus and ovaries (ages
      30-35 years); urinalysis with cytology (ages 25-35 years); history, examination,
      review of systems, education and genetic counseling regarding Lynch syndrome (age
      21 years). Regular colonoscopy was favored for at-risk persons without colorectal
      neoplasia. For individuals who will undergo surgical resection of a colon cancer,
      subtotal colectomy is favored. Evidence supports the efficacy of prophylactic
      hysterectomy and oophorectomy. CONCLUSIONS: The past 10 years have seen major
      advances in the understanding of Lynch syndrome. Current recommendations
      regarding cancer screening and prevention require careful consultation between
      clinicians, clinical cancer genetic services, and well-informed patients.

PMID- 17003400
TI  - An anniversary for cancer chemotherapy.

PMID- 17003401
TI  - Predicting and preventing hereditary colorectal cancer.

PMID- 17003402
TI  - Explaining, predicting, and treating HIV-associated CD4 cell loss: after 25 years
      still a puzzle.

PMID- 17003403
TI  - JAMA patient page. Colon cancer.

PMID- 17003405
TI  - Uncoordinated expression of myosin heavy chains and myosin-binding protein C
      isoforms in human extraocular muscles.
AB  - PURPOSE: To examine the distribution of myosin-binding protein C (MyBP-C) in
      human extraocular muscles (EOMs) and to correlate the myosin heavy chain (MyHC)
      and the MyBP-C composition of the fibers. METHODS: Samples from 17 EOMs, 3
      levator palpebrae (LP), and 6 limb muscles were analyzed with SDS-PAGE and
      immunoblot or processed for immunocytochemistry with monoclonal antibodies (mAbs)
      against MyBP-C-fast, MyBP-C-slow, MyHCIIa, MyHCI, MyHCsto, MyHCalpha-cardiac, and
      MyHCemb. RESULTS: In the limb muscle samples, fast fibers were labeled with anti
      MyBP-C-fast and anti-MyBP-C-slow, whereas the slow fibers were immunostained with
      anti-MyBP-C-slow only, in accordance with previous studies. In 11 EOM samples
      MyBP-C-fast was not detected, and weak staining with anti-MyBP-C-fast was seen
      only in a few fibers in the proximal part of 2 muscles. The mAb against MyBP-C
      slow labeled all fibers, but fibers containing MyHCI were generally more strongly
      stained. In the levator palpebrae, immunostaining with anti-MyBP-C-fast was
      present in some fibers labeled with anti-MyHCIIa and/or anti-MyHCeom. MyBP-C-fast
      and -intermediate were not detected biochemically in the EOMs. CONCLUSIONS: The
      lack of MyBP-C-fast and intermediate is an additional feature of the human EOM
      allotype. The true EOMs have a unique myofibrillar protein isoform composition
      reflecting their special structural and functional properties. The levator
      palpebrae muscle phenotype is intermediate between that of the EOMs and the limb
      muscles.

PMID- 17003404
TI  - Aqueous humor outflow: what do we know? Where will it lead us?

PMID- 17003406
TI  - Analysis of the Y402H variant of the complement factor H gene in age-related
      macular degeneration.
AB  - PURPOSE: Recent studies in U.S. populations have indicated that the Y402H variant
      of the complement factor H (CFH) gene contains a major risk susceptibility allele
      for age-related macular degeneration (AMD). This study was conducted to ascertain
      whether this is also true in a non-U.S. population and also whether the at-risk
      allele is associated with the clinical phenotype of disease and the age at
      diagnosis. METHODS: Two hundred thirty-six unrelated individuals with AMD and 144
      unrelated but ethnically matched control subjects were recruited and examined.
      All subjects completed a standard questionnaire, were given a fundus examination,
      and provided a blood sample for DNA extraction. Alleles of Y402H in the CFH gene
      were determined by use of a MALDI-TOF-based approach followed by statistical
      analysis. RESULTS: Individuals with AMD who had at least one copy of the C allele
      of Y402H had an increased risk of disease (odds ratio [OR] 2.98; 95% confidence
      interval [CI] 1.81-4.93) compared with cases with the T allele. On subgroup
      analysis, this risk was found to be most significant in individuals with
      neovascular disease (OR 4.34; 95% CI 1.94, 9.71). In addition, individuals with
      neovascular disease who were homozygous CC presented with a significant 7.0-year
      earlier age at diagnosis relative to those individuals who were homozygous TT.
      The population-attributable risk for the C allele ranged between 47% to 69%,
      depending on the AMD disease subtype. CONCLUSIONS: The C allele of Y402H
      represents a significant risk factor in individuals with AMD, and this effect is
      most pronounced in individuals with neovascular disease.

PMID- 17003407
TI  - Expression of the gene encoding poly(ADP-ribose) polymerase-1 is modulated by
      fibronectin during corneal wound healing.
AB  - PURPOSE: Poly(ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme essential in
      several cellular functions such as DNA repair, DNA transcription, carcinogenesis,
      and apoptosis. Expression of the PARP-1 gene is mainly dictated by the
      transcription factor Sp1. Fibronectin (FN), a component from the extracellular
      matrix transiently expressed at high levels during wound healing of the corneal
      epithelium, was reported to exert a positive influence on expression of the
      alpha5 integrin subunit gene promoter by altering the state of Sp1
      phosphorylation, a process that depended on the activation of the ERK signaling
      pathway. The present study was undertaken to investigate whether PARP-1 gene
      expression might be similarly regulated by FN through the same signaling pathways
      and attempted to link expression of this gene to corneal wound healing in vitro.
      METHODS: Expression of PARP-1, Sp1/Sp3, ERK1/2, phospho-ERK1/2, P38 and phospho
      P38 was monitored by Western blot in cultures of rabbit corneal epithelial cells
      (RCECs) grown on FN in the presence of inhibitors of the MAPK, PI3K, and P38
      signaling pathways. Electrophoretic mobility shift assays (EMSAs) were conducted
      to assess the binding of Sp1 and Sp3 in nuclear extracts from RCECs grown on FN
      in the presence of inhibitors. Plasmids bearing the PARP-1 promoter fused to the
      CAT reporter gene were also transfected into RCECs grown under similar culture
      conditions to assess the influence of these inhibitors on PARP-1 promoter
      activity. RESULTS: Expression of PARP-1, Sp1, and Sp3 increased considerably in
      RCECs grown on FN and translated into increased binding of Sp1 and Sp3 to their
      DNA target sites. In addition, FN increased PARP-1 promoter activity in a cell
      density-dependent manner. Inhibition of both the MAPK and the PI3K pathways
      entirely abolished these properties. CONCLUSIONS: PARP-1 gene expression was
      strongly activated by FN through alterations in the phosphorylation state of Sp1
      and Sp3 that resulted from the activation of the MAPK and PI3K signaling
      pathways, thereby suggesting that PARP-1 may play a critical function during the
      highly proliferative phase that characterizes wound healing of the corneal
      epithelium.

PMID- 17003408
TI  - Mitochondrial abnormalities in patients with LHON-like optic neuropathies.
AB  - PURPOSE: To investigate certain biochemical and molecular characteristics of
      mitochondria in patients with Leber hereditary optic neuropathy (LHON)-like optic
      neuropathies. METHODS: Patients who had LHON-like optic neuropathies in both eyes
      were selected from neuro-ophthalmology clinics. Evaluation included clinical
      examination, neuroimaging, and assessment of several mitochondrial parameters in
      the blood, including sequencing the entire mitochondrial (mt)DNA coding region,
      measuring relative mtDNA content, studying mitochondrial respiratory function in
      some patients, and sequencing the OPA1 and OPA3 genes. RESULTS: Thirty-five
      patients (21 men and 14 women; average age at onset 19.0 +/- 8.7 years) met
      inclusion and exclusion criteria for LHON-like optic neuropathies with median
      visual acuity approximately 20/200. Other hereditary retinopathies and optic
      neuropathies were unlikely because of inclusion and exclusion criteria, because
      ERGs were normal, and because no patient had pathogenic sequence changes in the
      OPA1 or OPA3 genes. Compared with control subjects, these patients had more
      potentially pathogenic nonsynonymous mtDNA changes, greater relative mtDNA
      content (P < 0.001), and less mitochondrial respiratory activity (P < 0.001).
      Only six patients (17%) had primary LHON mutations; however, even the 29 patients
      without primary LHON mutations had significant evidence of mitochondrial
      abnormalities. Mitochondrial haplogroup distribution was similar in patients and
      control subjects. CONCLUSIONS: Primary LHON mutations are less common in patients
      with LHON-like optic neuropathy selected from a clinical setting than in patients
      with LHON from multigenerational families. The results suggest that mitochondrial
      dysfunction plays a role in this type of optic neuropathy whether or not primary
      LHON mutations are present. This information has implications for diagnostic
      testing and for future investigations into mechanisms of disease.

PMID- 17003409
TI  - Differential mechanisms of conjunctival cell death induction by ultraviolet
      irradiation and benzalkonium chloride.
AB  - PURPOSE: To determine the molecular mechanisms of conjunctival cell death on
      exposure to the quaternary ammonium preservative benzalkonium chloride (BAC) and
      ultraviolet (UV) irradiation. METHODS: Chang conjunctival cells, either wild-type
      or stably transfected with various constructs encoding antiapoptotic molecules or
      transiently transfected with siRNA targeting the beclin-1 gene, were exposed to
      BAC or UV radiation Cell death was analyzed morphologically with fluorescence and
      electron microscopy, and molecular mechanisms of death were studied by using
      immunofluorescence, cell fractionation, caspase substrates, and immunoblot
      analysis, with or without immunoprecipitation. The main results were controlled
      in IOBA-NHC cells. RESULTS: Both agents induced cytochrome c release from the
      mitochondria, caspase activation, and nuclear chromatin condensation, suggesting
      caspase-dependent apoptosis. These events are prevented by stable expression of
      Bcl-2 protein. Both agents also induced a redistribution of Fas in plasma
      membrane rafts and the Fas-ligand-independent formation of a death-inducing
      complex leading to caspase-8 activation. Stable expression of either a dominant
      negative construct of Fas-associated death domain (FADD) or the long or short
      isoform of FADD-like interleukin-1-beta-converting enzyme inhibitory protein
      (FLIP) inhibited caspase-8 activation in response to both UV radiation and BAC.
      However, these proteins, as well as permeant peptides and baculovirus p35 caspase
      inhibitors, delayed more efficiently the UV irradiation-induced than the BAC
      induced nuclear chromatin condensation. BAC specifically activated a caspase
      independent pathway by inducing the mitochondrial release of apoptosis-inducing
      factor. BAC-treated cells contain autophagosomes/autolysosomes, a characteristic
      feature of autophagy, and siRNA-mediated downregulation of the beclin-1 gene,
      whose product is crucial for autophagy, increases BAC toxicity. CONCLUSIONS: UV
      irradiation induces typical, caspase-dependent cell death, whereas death induced
      by BAC associates features of caspase-dependent and -independent apoptosis
      counteracted by an autophagic process.

PMID- 17003410
TI  - Ocular abnormalities in mice lacking the Ski proto-oncogene.
AB  - PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is a developmental
      ocular malformation often associated with additional ocular abnormalities. This
      study involved a novel mouse model of PHPV, generated by a null mutation of the
      Ski proto-oncogene, that displays other anterior segment and retinal
      malformations often found in human cases of PHPV. METHODS: Morphologic and
      histologic analyses of Ski-/- mice were used to document ocular abnormalities in
      comparison to those of normal littermates. Immunohistochemical studies were used
      to examine the expression of relevant markers of ocular and vascular development
      including Pax6, beta-III tubulin, and Flk1. RESULTS: PHPV and microphthalmia were
      found in 100% of Ski-/- fetuses. Other abnormalities included anterior segment
      and lens dysgenesis, retinal folds, chorioretinal coloboma, and Peters anomaly.
      The severity was variable, even in a highly homogeneous genetic background. PHPV
      was characterized by the presence of retrolental fibrous and vascular tissue that
      did not express the neuronal marker beta-III tubulin, but was positive for Flk1
      expression and contained no obviously pigmented cells. CONCLUSIONS: The results
      show that normal ocular development requires the function of the Ski proto
      oncogene, and mice lacking Ski have many features associated with PHPV, and some
      similarities with Peters anomaly in humans. Defects in Ski-/- mice closely
      resemble those described in animals lacking several of the retinoic acid receptor
      genes, or in animals exposed to excess retinoic acid during gestation. Ski has
      been shown to repress transcription induced by retinoic acid signaling, and may
      thus affect ocular development by regulating RA signaling.

PMID- 17003411
TI  - Expression and polarized localization of the hemochromatosis gene product HFE in
      retinal pigment epithelium.
AB  - PURPOSE: Hereditary hemochromatosis is an autosomal recessive disorder of iron
      overload leading to oxidative stress. Mutations in HFE are responsible for
      approximately 90% of cases of this disease. HFE is the principal regulator of
      iron homeostasis, and the process involves interaction with transferrin receptor
      (TfR)-1, transferrin receptor (TfR)-2, and beta2-microglobulin (beta2M).
      Expression of HFE has not been investigated in the retina. In the present study,
      the expression of HFE and the HFE-interacting proteins TfR1, TfR2, and beta2M
      were analyzed in mouse retina. METHODS: RT-PCR was used to detect the expression
      of HFE mRNA in neural retina and the RPE-eyecup. Expression of HFE in intact
      retina was investigated by in situ hybridization, immunofluorescence, and
      immunogold electron microscopy. Expression of HFE-interacting proteins was also
      analyzed using similar techniques. RESULTS: RT-PCR showed predominant expression
      of HFE mRNA in the RPE-eyecup. In situ hybridization in intact retina revealed
      that HFE mRNA is expressed almost exclusively in RPE Immunofluorescence and
      immunogold electron microscopy showed that HFE protein was specifically
      associated with the basolateral membrane of RPE. Expression of the HFE
      interacting proteins TfR1, TfR2, and beta2M was also evident in the retina.
      CONCLUSIONS: This is the first report on the expression of HFE in the retina. The
      specific localization of HFE and its interacting proteins, TfR1 and TfR2, at the
      basolateral membrane of RPE is relevant to the regulation of iron homeostasis in
      this cell. Patients with hemochromatosis may have impairment of iron homeostasis
      in RPE, potentially contributing to age-related RPE dysfunction and retinal
      degeneration.

PMID- 17003413
TI  - Variations in primary open-angle glaucoma prevalence by age, gender, and race: a
      Bayesian meta-analysis.
AB  - PURPOSE: To quantify the variation in primary open-angle glaucoma (OAG)
      prevalence with age, gender, race, year of publication, and survey methodology.
      METHODS: Medline, EMBASE, and PubMed were searched for studies of OAG prevalence.
      Studies with defined population samplings were sought. Forty-six published
      observational studies of OAG prevalence (103,567 participants with 2509 cases of
      OAG) were identified for inclusion in the systematic review and meta-analysis.
      Data on the number of people and the number of cases of OAG by age, race, and
      gender were sought for each study. Additional information was obtained regarding
      whether the definition of glaucoma relied on raised intraocular pressure (IOP)
      and whether visual field examination was performed routinely on all individuals.
      Bayesian meta-analysis was used to model the associations between the log odds of
      OAG and age, race, gender, year of publication, method of visual field testing,
      and effect of reliance on IOP in the definition of OAG. RESULTS: Black
      populations had the highest OAG prevalence at all ages, but the proportional
      increase in prevalence of OAG with age was highest in white populations. The odds
      ratio per decade increase in age was 2.05 in white populations (95% credible
      interval, 1.91 to 2.18), 1.61 (95% credible interval, 1.53 to 1.70) in black
      populations, and 1.57 (95% credible interval, 1.46 to 1.68) in Asian populations.
      The average estimated prevalence in those older than 70 years of age was 6% in
      white populations, 16% in black populations, and 3% in Asian populations. After
      adjusting for age, race, year of publication, and survey methods, men were 1.37
      (95% credible interval, 1.22 to 1.53) times more likely than women to have OAG.
      The prevalence of OAG was one third lower in studies in which routine visual
      fields were not assessed and that used an IOP criterion in the definition of
      glaucoma; this effect was reduced to the null after adjustment for age, racial
      group, and year of publication. CONCLUSIONS: Although black populations had the
      highest prevalence of OAG at all ages, white populations showed the steepest
      increase in OAG prevalence with age. Men were more likely than women to have OAG.

PMID- 17003412
TI  - The Rx-like homeobox gene (Rx-L) is necessary for normal photoreceptor
      development.
AB  - PURPOSE: The retinal homeobox (Rx) gene plays an essential role in retinal
      development. An Rx-like (Rx-L) gene from Xenopus laevis has been identified. The
      purpose of this study was to analyze the function of Rx-L in the developing
      retina. METHODS: DNA-binding properties of Rx-L were analyzed by electrophoretic
      mobility shift assay (EMSA), with in vitro-translated proteins and radiolabeled
      oligonucleotide probe. The Rx-L expression pattern was analyzed by in situ
      hybridization using whole or sectioned embryos and digoxigenin-labeled antisense
      riboprobes. Rx-L loss of function was studied by using antisense morpholino
      oligonucleotides targeted to the Rx-L translation initiation site. Embryos
      injected with control or Rx-L morpholinos were analyzed at stage 41 or 45.
      RESULTS: Rx-L shares homology with Rx at the homeo-, OAR, and Rx domains, but
      lacks an octapeptide motif. Rx-L is expressed in the developing retina beginning
      in the early tailbud stage. In the maturing retina, Rx-L expression is restricted
      primarily to the developing photoreceptor layer and the ciliary marginal zone. Rx
      L can bind a photoreceptor conserved element-1 (PCE-1) oligonucleotide, an
      element conserved among all known photoreceptor gene promoters. In a promoter
      activity assay, Rx-L functions as a stronger transcriptional activator than Rx.
      Antisense morpholino-mediated knockdown of Rx-L expression resulted in a decrease
      in rhodopsin and red cone opsin expression levels in Xenopus retinas. Injection
      of the Rx-L antisense morpholino oligonucleotide also resulted in a decrease in
      the length of both rod and cone outer segments. CONCLUSIONS: The results suggest
      that Rx-L functions to regulate rod and cone development by activating
      photoreceptor-specific gene expression.

PMID- 17003414
TI  - Long-term visual acuity and its predictors after surgery for congenital cataract:
      findings of the British congenital cataract study.
AB  - PURPOSE: To report long-term postoperative visual acuity in a nationally
      representative group of children with congenital/infantile cataract and to
      investigate the factors associated with poor vision. METHODS: All children aged
      less than 16 years in the United Kingdom who had newly diagnosed
      congenital/infantile cataract in a 12-month period during 1995-1996 (the British
      Congenital/infantile Cataract Study) were traced through their managing
      ophthalmologists. Outcome data were collected at least 6 years after diagnosis,
      by using specifically designed questionnaires. Ordinal regression analysis
      identified factors associated with postoperative acuity. RESULTS: Of 153 children
      who had surgery, complete data were available in 122 (85%). Median age at follow
      up was 7 and 6.91 years, respectively, for bilateral and unilateral disease.
      Median age at surgery was 4.57 months in bilateral and 2.99 months in unilateral
      cases, with 40% and 45%, respectively, of children operated on by 3 months.
      Median (range) postoperative acuity was 6/18 (6/5, no perception of light) in
      bilateral and 6/60 (6/5, no perception of light) in unilateral disease. Poor
      compliance with occlusion was the factor most strongly associated with poorer
      acuity in both unilateral and bilateral disease: the odds of worse vision in
      unilateral cataract were 7.92 times greater with <50% versus 100% compliance (95%
      CI 1.68-37.26). In bilateral disease, odds of worse vision were reduced with each
      month of decreasing age at surgery (0.98, 95% CI 0.94-0.99), but increased by the
      presence of additional medical conditions (3.53, 95% CI 1.08-11.44) and the
      presence of postoperative ocular complications (2.94, 95% CI 1.38-6.51).
      CONCLUSIONS: These findings support a secular improvement in postoperative acuity
      in bilateral, and to a lesser extent, unilateral disease. Nevertheless early
      detection of congenital cataract through effective newborn screening and
      improving concordance with occlusion both remain priorities. Further improvements
      in outcomes in unilateral disease are necessary before parents can be advised
      universally that treatment will achieve a functionally useful "spare" eye.

PMID- 17003415
TI  - Estimating the yearly number of eyes with treatable neovascular age-related
      macular degeneration using a direct standardization method and a markov model.
AB  - PURPOSE: To estimate the number of treatable eyes with neovascular subfoveal age
      related macular degeneration (ARMD) in France. METHODS: A literature search for
      studies documenting neovascular ARMD incidence rates and direct standardization
      according to age and gender were performed. Projection to the year 2025 was based
      on OECD (Organization for Economic and Co-operation Development) data. A cohort
      of patients aged 75 years was simulated by a seven-state Markov model. The mean
      treatment duration was fixed arbitrarily at 2 years. The probability of ARMD in
      the second eye was fixed at 30% at 5 years. Monthly mortality incidence was
      modeled from INSEE (Institut National de la Statistique et des Etudes
      Economiques) mortality tables. The time horizon of the model was 25 years.
      Sensitivity analyses were performed. RESULTS: Based on the Rotterdam Study,
      30,192 citizens per year will develop ARMD in one eye. Among them, 17,585 will be
      neovascular and 13,805 neovascular subfoveal ARMD. Taking into account the second
      eye, mortality, and a 2-year treatment duration, the number of neovascular
      subfoveal treatable eyes yearly would be 37,019 by 2025. Treatment duration was
      the most sensitive parameter. The number of eyes would be 18,899, 53,204, 67,535,
      and 80,162, for treatment lasting 1, 3, 4, and 5 years, respectively. A 2% yearly
      increase is expected up to 2025, due to population aging and the 1950s baby boom.
      CONCLUSIONS: According to the study model, the yearly number of subfoveal
      neovascular ARMD treatable eyes in France will be 37,019 by 2025. Average
      treatment duration was the most sensitive parameter.

PMID- 17003416
TI  - Associations between childhood refraction and parental smoking.
AB  - PURPOSE: Motivated by pharmacologic findings linking nicotinic acetylcholine
      receptors to eye development in chicks, the authors studied whether the
      refractions of children who were passively exposed to cigarette smoke by their
      parents differed from those of nonexposed children. METHODS: A cross-sectional
      study was conducted among 323 patients (mean +/- SD age, 8.7 +/- 4.4 years;
      range, 1-20) in a tertiary care pediatric ophthalmology clinic. Half (162/323) of
      the subjects had strabismus. The accompanying parent completed a detailed
      questionnaire on parental smoking history and on putative risk factors for
      myopia. The results were compared to the subjects' cycloplegic refractions.
      RESULTS: If one or both parents ever smoked, their children had a lower myopia
      prevalence (12.4% vs. 25.4%; P = 0.004) and more hyperopic mean refractions (1.83
      +/- 0.24 vs. 0.96 +/- 0.27 diopters; P = 0.02) than those whose parents never
      smoked. Smoking by either parent during the mother's pregnancy had a similar
      effect on the child's refraction. The associations largely persisted, both in
      multivariate models that included adjustments for the child's age, child's body
      mass index, child's nearwork activity, parental myopia, and parental education
      and also in analysis by subgroups stratified by strabismus status. CONCLUSIONS:
      Despite the complex constituents of cigarette smoke, neuropharmacology
      perspectives may prove useful in the development of new hypotheses to understand
      the mechanisms governing refractive development, not only in experimental animals
      but also in children. The associations of less prevalent myopia and a more
      hyperopic mean refraction with both prenatal and childhood exposures to tobacco
      smoke suggest that nongenetic, environmental exposures may have long-term
      influences on refraction and that further study of the role of nicotinic
      acetylcholine receptors in refractive development is warranted.

PMID- 17003417
TI  - Identical excimer laser PTK treatments in rabbits result in two distinct haze
      responses.
AB  - PURPOSE: To obtain objective light-scattering measurements to test a hypothesis
      that identical PTK treatments cause distinct low- and high-level light-scattering
      responses in rabbit corneas. METHODS: An excimer laser was used to produce
      identical 6-mm diameter phototherapeutic keratectomy treatments (PTK) in 32
      pigmented rabbits. Eyes were treated by performing a 40-microm epithelial
      ablation, followed by a 100-mum stromal PTK. Objective scattering measurements
      were made before treatment, weekly up to 5 weeks, and then biweekly to 9 weeks.
      Confocal microscopy was performed on several corneas at 4 and 7 weeks. RESULTS:
      Mean scattering levels split into distinct low- and high-scattering groups 2
      weeks after treatment and remained distinct until week 7 (P < 0.003). Scattering
      in the low group reached a broad peak that lasted from weeks 2 to 4 at
      approximately 3 times the pretreatment level. Scattering in the high group peaked
      at 3 weeks at approximately 12 times the pretreatment level. Scattering levels
      diminished after reaching their peaks. Confocal images showed a band of highly
      reflective material in the anterior stroma that extended much deeper in corneas
      from the high group. The reflective band in the highly scattering corneas
      obscured the posterior stroma from view for up to 5 weeks. CONCLUSIONS:
      Quantitative scattering data obtained with the scatterometer suggest that
      identical PTK treatments indeed result in distinct low- and high-level light
      scattering responses in rabbits.

PMID- 17003418
TI  - Transglutaminase participates in UVB-induced cell death pathways in human corneal
      epithelial cells.
AB  - PURPOSE: Ultraviolet light (UVB) is known to cause apoptosis in human corneal
      epithelial cells. This study evaluates the role of transglutaminase in regulating
      tumor necrosis factor (TNF) receptor clustering as well as caspase activation in
      UVB-induced apoptosis in human corneal epithelial cells. METHODS: A human corneal
      epithelial cell line was used. A single dose of UVB (20 mJ/cm2) was used as a
      stimulus. Cell viability and cell death were investigated by MTT, terminal
      deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL),
      and caspase-3 assays. Immunofluorescent staining was used to investigate TNF
      receptor-I clustering at various time intervals after UVB. Short interfering RNA
      was used to knock down transglutaminase-2 expression. Fluorescein-cadaverine
      uptake was used to assess transglutaminase activity. A noncovalent peptide
      delivery system was used to transfect guinea pig liver transglutaminase into
      corneal epithelial cells. RESULTS: UVB increased transglutaminase activity,
      reduced cell viability, and increased TUNEL staining. UVB or TNF-alpha promoted
      TNF-receptor-I clustering, a process inhibited by the transglutaminase inhibitor,
      mono-dansyl cadaverine. UVB also increased activated caspase-3, in a manner
      suppressible by mono-dansyl cadaverine. Intracellular delivery of exogenous
      transglutaminase markedly increase caspase-3 activation compared with the vehicle
      control. CONCLUSIONS: Transglutaminase enzymatic activity is involved in corneal
      epithelial cell death after UVB and appears to participate in two steps
      regulating this process, clustering of TNF receptor-I and caspase-3 activation.

PMID- 17003419
TI  - Factors affecting the morbidity of contact lens-related microbial keratitis: a
      population study.
AB  - PURPOSE: To examine factors influencing the severity of soft contact lens (SCL)
      related microbial keratitis. METHODS: Cases were detected via surveillance
      studies in Australia and New Zealand. Factors affecting disease severity (costs,
      days of symptoms, and 2 or more lines of vision loss) were examined and included
      age; gender; delay in SCL removal, seeking consultation, or receiving treatment;
      overnight wear; SCL material (hydrogel or silicone hydrogel [SiH]); and causative
      organism. RESULTS: Two hundred ninety-seven cases were identified: 61% female,
      age: 35 +/- 13 years (mean +/- SD). Treatment costs were (median [interquartile
      range]) $760 [1859] and indirect costs were $468 [1810]. Patients were
      symptomatic for 7 [11] days, and vision loss occurred in 14.3% of cases. Cases
      with pathogenic causative organisms (66/297, 22%) were 11.4 times (95% confidence
      interval [CI], 4.2-30.9) more likely to result in vision loss, had longer
      duration of symptoms (21 [40] vs. 6 [8] days, P < 0.001) and incurred higher
      costs (5,512 [14,733] vs. 1,048[8,325], P < 0.001). Delays (>12 hours) before
      treatment increased the likelihood of vision loss (P = 0.048) disease duration (P
      = 0.004), and associated costs (P = 0.009). Remoteness increased the risk of
      vision loss (odds ratio [OR] = 5.1; 95% CI 1.6-16.6), and individuals over 28
      years of age had longer disease duration (P = 0.02). In overnight wear and after
      adjustment for culture result and treatment delays, SiH wearers had slightly
      shorter disease duration (4 [4] vs. 7 [10] days, P = 0.02) but a rate of vision
      loss and cost similar to those of hydrogel wearers. CONCLUSIONS: The causative
      organism was the major determinant of severity; however, modifiable factors such
      as delays in treatment had considerable influence. Duration of symptoms was
      shorter in SiH wearers, but other factors dominated disease outcome in this
      population study.

PMID- 17003420
TI  - Tear film osmolarity: determination of a referent for dry eye diagnosis.
AB  - PURPOSE: To determine new referents, or cutoff levels for tear film
      hyperosmolarity in the diagnosis of keratoconjunctivitis sicca (KCS) and to
      assess their effectiveness in independent patient groups. METHOD: A meta-analysis
      was performed on published data for tear osmolarity in samples of normal eyes and
      various subtypes of dry eye, and pooled estimates of the mean and standard
      deviations for normal and (all) dry eye subjects were determined. Diagnostic
      referents were derived from the intercept between the distributions of osmolarity
      in the two samples and from receiver operator characteristic (ROC) curves. This
      referent was tested for effectiveness of diagnosis in independent groups with
      normal and dry eyes. RESULTS: An osmolarity referent of 315.6 mOsmol/L was
      derived from the intercept of the distribution curves, and 316 mOsmol/L from the
      ROC curve. When applied to independent groups of normal and dry eye subjects a
      value of 316 mOsmol/L was found to yield sensitivity of 59%, specificity of 94%,
      and an overall predictive accuracy of 89% for the diagnosis of dry eye syndrome.
      CONCLUSIONS: Tear hyperosmolarity, defined by a referent of 316 mOsmol/L, was
      superior in overall accuracy to any other single test for dry eye diagnosis
      (Lactoplate, Schirmer test, and Rose Bengal staining), even when the other test
      measures were applied to a diagnosis within the sample groups from which they
      were derived. For overall accuracy in the diagnosis of dry eye, the osmolarity
      test was found to be comparable with the results of combined (in parallel or
      series) tests.

PMID- 17003421
TI  - Amniotic membrane for ocular surface reconstruction: donor variations and the
      effect of handling on TGF-beta content.
AB  - PURPOSE: Amniotic membrane (AM) transplantation is an accepted procedure in
      ocular surgery. However, little is known of the interdonor and intradonor
      variability within the membrane. In addition, the effects of the methods of
      processing, storage, and preoperative preparation on the membrane are not fully
      elucidated. The purpose of this study was to use TGF-beta as an example to
      investigate interdonor and intradonor variability and to determine the effect of
      "handling " on TGF-beta1 within fresh, processed and stored, and transplantation
      ready AM (TRAM). METHODS: Seventeen human AMs, both fresh and handled, were
      analyzed for TGF-beta1 by real-time polymerase chain reaction,
      immunohistochemistry, SDS-PAGE, and Western blotting. RESULTS: TGF-beta1 was the
      highest normalized expressed isoform of TGF-beta in all samples, but it varied
      between membranes of different donors and at different sites within the same
      membrane. The highest concentration was noted in the spongy layer. Removal of the
      spongy layer successfully removed the bulk of TGF-beta1 from TRAM. Latency
      associated protein (LAP) and a latent TGF-beta-binding protein (LTBP) were also
      detected. CONCLUSION: TGF-beta1 is present in various regulatory forms in the AM.
      A degree of intermembrane and intramembrane variation is modified by handling.
      Unless a standardized protocol is adopted that delivers a membrane with
      consistent constituents, clinical outcomes may vary and comparisons may be
      invalid.

PMID- 17003422
TI  - Role of Rac1 in fibronectin-induced adhesion and motility of human corneal
      epithelial cells.
AB  - PURPOSE: The fibronectin-integrin system plays an important role in adhesion and
      migration of corneal epithelial cells and thereby contributes to epithelial wound
      healing. The role of Rac1, a member of the Rho family of GTPases, in the
      intracellular signaling responsible for regulation of the adhesion and motility
      of corneal epithelial cells by fibronectin was examined. METHODS: Simian virus 40
      transformed human corneal epithelial (HCE) cells were plated on fibronectin or on
      bovine serum albumin as a control. Cell motility was monitored by time-lapse
      video microscopy. The actin cytoskeleton and focal adhesions were detected by
      staining of cells with rhodamine-phalloidin and antibodies to phosphotyrosine,
      respectively. The activation of Rac1 and phosphorylation of its effector PAK were
      evaluated with a pull-down assay and immunoblot analysis, respectively. The
      effects of mutant forms of Rac1 were determined by cell transfection. RESULTS:
      HCE cells plated on fibronectin manifested greater levels of cell adhesion and
      motility than did those plated on bovine serum albumin. Fibronectin also induced
      the accumulation of F-actin and the formation of focal adhesions at the cell
      periphery as well as the activation of Rac1 and the phosphorylation of PAK.
      Expression of the dominant negative mutant Asn17Rac1 inhibited the effects of
      fibronectin on cell adhesion and motility, the actin cytoskeleton, and focal
      adhesions. Expression of the constitutive active mutant Val12Rac1 mimicked the
      effects of fibronectin on F-actin and focal adhesions. CONCLUSIONS: Rac1 is
      necessary for the promotion of HCE cell adhesion and motility by fibronectin. It
      therefore probably plays an important role in corneal wound healing.

PMID- 17003423
TI  - Age differences in cyclin-dependent kinase inhibitor expression and rb
      hyperphosphorylation in human corneal endothelial cells.
AB  - PURPOSE: Human corneal endothelial cells (HCECs) are considered to be
      nonreplicative in vivo; however, isolated HCECs can be cultured and grown
      successfully, indicating that they retain proliferative capacity. This capacity
      to replicate tends to decrease with donor age. Cyclin-dependent kinase inhibitors
      (CKIs) are important negative regulators of the cell cycle. Of those CKIs,
      p16INK4a, p21WAF1/Cip1, and p27Kip1 are expressed in corneal endothelium. To help
      reveal the mechanism of this age-related difference, the relative expression of
      those CKIs and the kinetics of hyperphosphorylation of the retinoblastoma
      protein, Rb, were analyzed in HCECs from various aged donors. METHODS: Fresh
      frozen sections of corneas from an 18-year-old and a 74-year-old donor were
      immunostained to reveal the expression and localization of the three CKIs in
      corneal endothelium in situ. HCECs from eight donors of various ages were
      isolated and cultured until they reached passage 4. After the cells reached
      confluence, total protein was extracted, and the relative expression of
      p16(INK4a), p21WAF1/Cip1, and p27Kip1 was determined by Western blot analysis. A
      parallel analysis was performed with primary cultures of HCECs obtained from
      eight different donors. Subconfluent passage 2 HCECs from eight donors were serum
      starved and, at different times after growth factor stimulation, protein was
      extracted, and Western blot analysis was used to compare the overall expression
      of Rb protein and the kinetics of Rb hyperphosphorylation. RESULTS:
      Immunocytochemistry confirmed the expression and nuclear localization of
      p16(INK4a), p21WAF1/Cip1, and p27Kip1 in HCECs in situ. Western blot studies
      revealed an age-related increase in p16INK4a and p21WAF1/Cip1 protein expression
      in cultured HCECs. Expression of p27Kip1 tended to decrease with the donor's age
      in passage-4 cells; however, there was no significant difference in p27Kip1
      expression level between young and older donors in primary cultured HCECs. No age
      related difference in total Rb protein was observed in the Western blots;
      however, the rate of Rb hyperphosphorylation was significantly slower in HCECs
      from older donors. CONCLUSIONS: p16(INK4a), p21WAF1/Cip1, p27Kip1, and Rb were
      all expressed in HCECs, regardless of donor age. Age-related differences in the
      relative expression of p16INK4a and p21WAF1/Cip1 and in the kinetics of Rb
      hyperphosphorylation led to the conclusion that, in addition to the normal
      inhibitory activity of p27Kip1, there is an age-dependent increase in negative
      regulation of the cell cycle by p16INK4a and p21WAF1/Cip1. This additional
      molecular mechanism may be responsible, at least in part, for the reduced
      proliferative response observed in HCECs from older donors.

PMID- 17003424
TI  - The zebrafish cornea: structure and development.
AB  - PURPOSE: To evaluate the zebrafish as a model for the studies of corneal
      development and disease. METHODS: Zebrafish embryos and larvae at various stages
      of development were used for documenting corneal morphogenesis and
      differentiation. Corneal samples were collected from embryos, larvae, and adult
      zebrafish for histologic and electron microscopy analysis. Expression patterns of
      corneal polypeptides were investigated by immunostaining of sections. RESULTS:
      The zebrafish cornea develops rapidly during embryogenesis, so that its three
      major layers, the epithelium, the stroma, and the endothelium, are well formed by
      day 3 postfertilization. The subsequent steps of corneal differentiation, such as
      the thickening of the corneal stroma, proceed relatively slowly. Several
      polypeptides are highly enriched in the epithelium or the stroma of the larval
      and adult zebrafish cornea and are excellent markers of corneal differentiation.
      CONCLUSIONS: Development and differentiation of the zebrafish cornea are easily
      accessible to analysis. Anatomic and ultrastructural characterization of the
      zebrafish cornea demonstrates many similarities to the human cornea and provides
      the basis for the use of the zebrafish model both to analyze the basic genetic
      mechanisms of corneal development and to study the causes of corneal disease.

PMID- 17003425
TI  - Relationships between central tear film thickness and tear menisci of the upper
      and lower eyelids.
AB  - PURPOSE: To investigate the relationship between central tear film thickness
      (TFT) and tear menisci of the upper and lower eyelids using real-time optical
      coherence tomography (OCT). METHODS: Both eyes of healthy subjects were imaged
      with a real-time OCT to obtain height, curvature, and area of upper and lower
      tear menisci simultaneously. Central TFT was indirectly measured by calculating
      the difference between baseline measurements of the central corneal thickness
      plus tear film and the true corneal thickness obtained after instillation of
      artificial tears. Results from two normal blinks were obtained from one eye at
      each visit and repeated the next day. RESULTS: The average central TFT was 3.4 +/
      2.6 microm. The upper tear meniscus curvature, height, and area were 239 +/- 112
      microm, 268 +/- 68 microm, and 22,732 +/- 11,974 microm2 respectively. There were
      no significant differences in curvatures, heights, or areas between upper and
      lower tear menisci, nor were there any differences in measured variables between
      the two blinks at each visit or between the two repeated visits in the right and
      left eye groups (P > 0.05). The upper and lower tear menisci in each eye group on
      each day correlated strongly with curvature, height, and area (all P < or =
      0.03). However, no tear meniscus variable was a significant predictor of TFT (all
      P > 0.44). CONCLUSIONS: OCT is a promising tool in the measurements of TFT and
      dimensional variables of tear menisci. Upper and lower tear menisci have nearly
      identical dimensions.

PMID- 17003426
TI  - Activation of CD36 inhibits and induces regression of inflammatory corneal
      neovascularization.
AB  - PURPOSE: This study was undertaken to investigate the role of the antiangiogenic
      receptor CD36 during inflammatory corneal neovascularization (CNV). METHODS: In a
      murine model of inflammatory CNV, CD36 expression was evaluated by RT-PCR and
      immunofluorescence. Mice subjected to CNV were treated topically (thrice daily)
      with CD36 functionally neutralizing antibodies against the oxidized low-density
      lipoprotein (oxLDL) and thrombospondin (TSP)-1 sites (clones JC63.1 and FA6-152,
      respectively). Neovascularization was analyzed by CD31-immunostained corneal
      flatmounts. The role of the less characterized oxLDL site during angiogenesis was
      elucidated by using the CD36 ligand 1-palmitoyl 2-(5'-oxovaleroyl)
      phosphatidylcholine (POVPC; 50, 100 microg/mL) 24 hours after corneal injury for
      7 days, whereas in angioregressive studies, POVPC treatments were initiated 10
      days after induction of CNV. In this process, VEGF expression was also studied.
      Effects of CD36 activation were further examined ex vivo using the mouse aortic
      ring assay. RESULTS: CD36 expression was upregulated after corneal injury; CD36
      was expressed in corneal epithelium, limbus, invading microvessels, and stromal
      macrophages. Blocking CD36 activity with FA6-152 significantly increased CNV (P
      <0.001). Conversely, activating CD36 with POVPC dose dependently inhibited CNV (P
      = 0.003); this effect was blocked by JC61.3. POVPC also significantly regressed
      preformed blood vessels (P < 0.001). Ex vivo experiments on aortic rings
      confirmed the angioinhibitory and -regressive effects of POVPC. Because corneal
      macrophages express CD36 and may partake in angiogenesis via VEGF-A secretion, we
      surmised that VEGF-A could be modulated by CD36. Indeed, POVPC downregulated VEGF
      A expression in a time-dependent fashion (P < 0.001), whereas FA6-152 induced its
      expression (P < 0.05). CONCLUSIONS: CD36 is involved both physiologically and
      pharmacologically in inhibition and regression of CNV, by direct effect on
      endothelial cells and partly by negatively regulating VEGF expression in
      macrophages.

PMID- 17003427
TI  - Aquaporin-3-dependent cell migration and proliferation during corneal re
      epithelialization.
AB  - PURPOSE: To determine a role for the water- and glycerol-transporting protein
      aquaporin-3 (AQP3) in mammalian corneal epithelium, where it is expressed but has
      no known function. METHODS: Corneal epithelial water and glycerol permeabilities
      were measured in living wild-type and AQP3-null mice using calcein fluorescence
      quenching and 14C-glycerol-uptake assays, respectively. After removal of the
      corneal epithelium by scraping, re-epithelialization was followed by fluorescein
      staining. The contribution of AQP3-facilitated cell migration to corneal re
      epithelialization was assessed using an organ culture model, in which initial
      resurfacing results from epithelial cell migration, as shown by BrdU analysis and
      5-fluorouracil insensitivity, and by scratch wound assay using primary cultures
      of corneal epithelial cells from wild-type versus AQP3-null mice. Involvement of
      AQP3 in epithelial cell proliferation was investigated by morphometric and BrdU
      analysis of histologic sections, and by measurement of [3H]thymidine uptake in
      primary cultures of corneal epithelial cells. RESULTS: AQP3 deficiency did not
      alter corneal epithelial thickness, morphology, or glycerol content, though both
      water and glycerol permeabilities were reduced. Time to corneal re
      epithelialization in vivo was significantly delayed in AQP3-null mice compared to
      wild-type mice. Delays were also found in organ and primary cultures,
      demonstrating a distinct defect in cell migration arising from AQP3 deletion.
      Delayed restoration of full-thickness epithelia of AQP3-null mice over days after
      scraping suggested a separate defect in epithelial cell proliferation, which was
      confirmed by reduction in proliferating BrdU-positive cells in AQP3-deficient
      mice during healing, and by reduced proliferation in primary cultures of corneal
      epithelial cells from AQP3-null mice. CONCLUSIONS: The significant impairment in
      corneal re-epithelialization in AQP3-deficient mice results from distinct defects
      in corneal epithelial cell migration and proliferation. The results provide
      evidence for involvement of an aquaporin in cell proliferation and suggest AQP3
      induction as a possible therapy to accelerate the resurfacing of corneal defects.

PMID- 17003428
TI  - Standard microlithographic mosaics to assess endothelial cell counting methods by
      light microscopy in eye banks using organ culture.
AB  - PURPOSE: To develop standard microscopic hexagonal mosaics mimicking the human
      corneal endothelium for quality control of endothelial cell density (ECD)
      measurement and verification of cell counting strategy by light microscopy in eye
      banks using organ culture. METHODS: A standard slide, the Keratotest, was
      developed with 10 laser-engraved mosaics and different predetermined "cell"
      densities representing the range of ECDs observed routinely. Horizontal and
      vertical micrometric scales were etched adjacently to each mosaic, and a standard
      microscopy resolution test pattern was included. The Keratotest was applied to
      assess the reliability of a computer-assisted analyzer developed for corneal
      endothelial evaluation based on light microscopy images. RESULTS: The Keratotest
      consisted of 10 microlithographic homogeneous mosaics of 1-mm2 printed area and
      1.2-microm cell boundary thickness. The micrometric scale associated with each
      mosaic aided in simultaneous verification of microscope calibration, and the test
      pattern aided in checking the microscope resolution. The design was unalterable
      and reproducible, and the glass slide incorporated in a carbon fiber support
      ensured easy handling and safe transport. Evaluation of the Keratotest mosaics by
      the computer-assisted analyzer found a high level of agreement (error margin
      between +0.12 and -0.46%) with the laser-engraved cell density. CONCLUSIONS: This
      prototype device enabled assessment of reliability of ECD measurement in eye
      banks. It also allowed verification of the calibration and resolution of light
      microscopes. Periodic validation of counting procedure in eye banks with mosaics
      of known "cell" densities should be useful for standardization of donor corneal
      tissue quality control.

PMID- 17003429
TI  - The effects of retinal abnormalities on the multifocal visual evoked potential.
AB  - PURPOSE: To examine the effects on the amplitude and latency of the multifocal
      visual evoked potential (mfVEP) in retinal diseases associated with depressed
      multifocal electroretinograms (mfERG). METHODS: Static automated perimetry (SAP),
      mfERGs, and mfVEPs were obtained from 15 individuals seen by neuro
      ophthalmologists and diagnosed with retinal disease based on funduscopic
      examination, visual field, and mfERG. Optic neuropathy was ruled out in all
      cases. Diagnoses included autoimmune retinopathy (n = 3), branch retinal arterial
      occlusion (n = 3), branch retinal vein occlusion (n = 1), vitamin A deficiency (n
      = 1), digoxin/age-related macular degeneration (n = 1), multiple evanescent white
      dot syndrome (n = 1), and nonspecific retinal disease (n = 5). Patients were
      selected from a larger group based on abnormal mfERG amplitudes covering a
      diameter of 20 degrees or greater. RESULTS: Fourteen (93%) of 15 patients showed
      significant mfVEP delays, as determined by either mean latency or the probability
      of a cluster of delayed local responses. Thirteen of 15 patients had normal mfVEP
      amplitudes in regions corresponding to markedly reduced or nonrecordable mfERG
      responses. These findings can be mimicked in normal individuals by viewing the
      display through a neutral-density filter. CONCLUSIONS: Retinal diseases can
      result in mfVEPs of relatively normal amplitudes, often with delays, in regions
      showing decreased mfERG responses and visual field sensitivity loss.
      Consequently, a retinal problem can be missed, or dismissed as functional, if a
      diagnosis is based on an mfVEP of normal or near-normal amplitude. Further, in
      patients with marked mfVEP delays, a retinal problem could be confused with optic
      neuritis, especially in a patient with a normal appearing fundus.

PMID- 17003430
TI  - The VF-14 and psychological impact of amblyopia and strabismus.
AB  - PURPOSE: To assess the impact of amblyopia, strabismus and glasses on subjective
      visual and psychological function among amblyopes. METHODS: Questionnaires were
      administered to 120 teenagers with amblyopia (cases), with residual amblyopia
      after treatment, or with or without strabismus and 120 control subjects
      (controls) Cases underwent ophthalmic examination including cycloplegic
      refraction. Two questionnaires (visual function 14 [VF-14] and a newly designed
      eight-item questionnaire) were administered to assess the psychological impact
      score of general daily life, having a weaker eye, glasses wear, and current
      noticeable strabismus. Questionnaires were validated in 60 subjects in each group
      by a second administration of the questionnaire. The VF-14 scores, psychological
      impact scores, and clinical data were compared. RESULTS: The VF-14 and
      psychological impact scores were highly reproducible. The mean VF-14 score for
      the control group was 95.5 and for the cases was 78.9 (P < 0.0001), but the
      scores did not correlate with the severity of amblyopia. The psychological impact
      score in general daily life was sensitive in discriminating between mild (median
      score 31) and moderate to severe (median score 56) amblyopes (P < 0.02). The
      cases segregated into two clear groups; those who scored high (large detrimental
      psychological impact) on psychological impact, with subjectively noticeable
      manifest strabismus, and those who scored low (low detrimental psychological
      impact), without noticeable strabismus. The subjective experience of patching
      treatment differentiated the two groups best of all. CONCLUSIONS: Subjective
      visual and psychological functions are altered compared with normal subjects due
      to amblyopia, strabismus, and a previous unpleasant patching experience. The mean
      VF-14 score was similar to that previously published for patients with glaucoma.
      The study underlines that amblyopia and/or strabismus have an impact on
      teenagers' subjective visual function and well-being.

PMID- 17003431
TI  - Predictors and a remedy for noncompliance with amblyopia therapy in children
      measured with the occlusion dose monitor.
AB  - PURPOSE: Noncompliance is one of the limiting factors in the success of occlusion
      therapy for amblyopia. Electronic monitoring was used to investigate predictors
      of noncompliance, and, in a prospective randomized clinical trial, determined the
      effectiveness of an educational program. METHODS: Compliance was measured
      electronically during 1 week every 3 months in 310 newly diagnosed amblyopic
      children. The family's demographic parameters and the child's clinical parameters
      were assessed for their influence on the level of compliance. In addition to
      standard orthoptic care, children were randomized to receive an educational
      cartoon story, reward stickers, and an information sheet for the parents
      (intervention group), or a picture to color (reference group). These and the
      electronic device were distributed during home visits by researchers. The primary
      outcome measure was the percentage of compliance (actual/prescribed occlusion
      time) in the two groups. The secondary outcome measure was the influence of
      demographic and clinical factors on compliance. RESULTS: Compliance was
      associated with parental fluency in the national language, country of origin,
      level of education, and initial visual acuity of the child. During the first 1
      week measurement period children in the intervention group had better compliance
      than the reference group had (78% +/- 32% vs. 57% +/- 40%; P < 0.0001), and fewer
      children were not occluded at all (3 vs. 23 in the reference group; P < 0.0001).
      This difference remained throughout the study period. CONCLUSIONS: Poor parental
      fluency in the national language, a low level of education, and poor acuity at
      the start of treatment were predictors of low compliance. An educational program
      primarily aimed at the child improved compliance and reduced the number of
      children who did not comply with occlusion at all.

PMID- 17003432
TI  - Evidence for ocular motor deficits in developmental dyslexia: application of the
      double-step paradigm.
AB  - PURPOSE: Dyslexia is a language-based learning disability characterized by
      difficulties with reading, spelling, and writing. Persons with dyslexia often
      have deficits in processing rapid temporal sensory information. There is also
      evidence of sensorimotor deficits in persons with dyslexia. Whether these
      deficits include ocular motor problems is still an open question. Some previous
      studies have shown an increased saccadic latency in dyslexics, whereas others
      have not reproduced this finding. The purpose of the present study was to
      investigate saccadic latency in young adults with dyslexia during the double-step
      paradigm, a task that requires rapid sequential visual information processing and
      saccade generation. The study hypothesis was that dyslexics have a longer
      saccadic latency in the second orthogonal saccade, a task that nondyslexics
      parallel process and perform rapidly. METHODS: Eight students with dyslexia and
      eight age-matched control subjects participated in the study. Their eye movements
      were monitored with the scleral search coil technique in simple saccade trials
      and in the double-step paradigm. The second saccade was either orthogonal or
      colinear to the first. Intersaccadic interval and latency were calculated for the
      second saccade. RESULTS: No difference in saccadic latency was found for colinear
      second saccades; however, dyslexics had significantly longer latencies for
      orthogonal second saccades. This included a subset of subjects who had longer
      latencies for orthogonal than for colinear saccades. CONCLUSIONS: The findings
      indicate that under certain conditions, when the demand for rapid visual
      information processing is high and a rapid saccade sequence is required, some
      persons with dyslexia show ocular motor deficits manifested by longer saccadic
      latencies.

PMID- 17003433
TI  - Ocular response analyzer versus Goldmann applanation tonometry for intraocular
      pressure measurements.
AB  - PURPOSE: To establish correlations between intraocular pressure (IOP)
      measurements obtained with the ocular response analyzer (ORA) and the Goldmann
      applanation tonometer (GAT). The effects of central corneal thickness on the
      measures obtained were also examined. METHODS: This was a cross-sectional study.
      IOP was determined in 48 eyes of 48 patients with glaucoma In all patients,
      central corneal thickness (CCT) was measured by ultrasound pachymetry. RESULTS:
      ORA readings were consistently higher than GAT measurements (Goldmann-correlated
      IOP - IOP GAT mean difference, 7.2 +/- 3.5 mm Hg; corneal-compensated IOP - IOP
      GAT mean difference, 8.3 +/- 4.0 mm Hg) However, differences were not constant
      and increased with increasing IOP GAT readings, both with respect to Goldmann
      correlated IOP (slope = 0.623, P < 0.0001) and corneal-compensated IOP (slope =
      0.538, P < 0.0001). Both pressure measurements provided by the ORA showed
      significant correlation with CCT (CCT versus Goldmann-correlated IOP: r = 0.460,
      P = 0.001; CCT versus corneal-compensated IOP: r = 0.442, P = 0.001). No
      significant effects of corneal curvature or refraction on any of the pressures
      were observed. CONCLUSIONS: The ORA significantly overestimates IOP compared with
      the GAT. Differences between both sets of measures increase as the GAT-determined
      IOP increases. ORA readings seem to be affected by central corneal thickness.

PMID- 17003434
TI  - Improving the repeatability of topographic height measurements in confocal
      scanning laser imaging using maximum-likelihood deconvolution.
AB  - PURPOSE: To evaluate maximum likelihood (ML) blind deconvolution as a technique
      for improving the repeatability of topographic height measurements obtained from
      scanning laser tomography (Heidelberg Retinal Tomograph [HRT]; Heidelberg
      Engineering, Heidelberg, Germany). METHODS: ML blind deconvolution is an image
      processing technique that estimates the original scene from a degraded image.
      This technique has been used in confocal scanning laser microscopy to remove "out
      of-focus" haze in three-dimensional confocal image stacks. ML blind deconvolution
      requires no prior estimation of the point-spread function (PSF), as opposed to
      classic linear deconvolution methods. Instead, the algorithm estimates an initial
      PSF based on the optical setup of the confocal scanning device and optics of the
      eye and iteratively proceeds to a solution. The improvement in repeatability of
      height measurements from mean topography images within scan (intrascan) and
      between scans (interscan) afforded by ML deconvolution was evaluated in a test
      retest series of HRT images from 40 ocular hypertensive and glaucomatous patients
      with varying degrees of media opacity. RESULTS: There was an improvement in
      intrascan repeatability in 38 out of the 40 mean topography images (median
      improvement 2.5 microm, inter-quartile range 2.19, P < 0.001), and an improvement
      in interscan repeatability in 33 of the 40 mean topographies (median improvement,
      1.0 microm, interquartile range 3.49, P < 0.001). There was a positive
      association between the magnitude of the improvement in repeatability and the
      level of mean pixel height standard deviation (MPHSD), intrascan (P = 0.004) and
      interscan (P = 0.002). CONCLUSIONS: ML blind deconvolution algorithm improves the
      repeatability of topographic height measurements from the HRT. This improvement
      was greater in patients with poorer quality images.

PMID- 17003435
TI  - Effect of 24-hour corneal biomechanical changes on intraocular pressure
      measurement.
AB  - PURPOSE: To study 24-hour changes of corneal biomechanical properties and their
      influences on measurement of intraocular pressure (IOP). METHODS: Fifteen healthy
      young volunteers (age range, 20-25 years) were housed for 1 day in a sleep
      laboratory. Sitting and supine central corneal thickness (CCT) were measured
      every 2 hours with an ultrasonic pachymeter. Sitting IOP and corneal hysteresis,
      an indicator of viscoelasticity, were measured with a noncontact tonometer.
      RESULTS: There were consistent 24-hour variations of CCT and IOP for the group.
      Nocturnal mean CCT and nocturnal mean IOP were significantly higher than the
      diurnal mean CCT and diurnal mean IOP, respectively. The peak CCT occurred at
      1:30 to 5:30 AM and the trough CCT at 1:30 PM. The peak IOP occurred at 5:30 AM
      and the trough IOP at 9:30 PM. Cosine fits of each subject's 24-hour CCT and IOP
      data showed synchronized rhythms. The phase timing of 24-hour CCT rhythm was
      significantly earlier than the phase timing of 24-hour IOP rhythm. Twenty-four
      hour variation of corneal hysteresis was inconsistent and cosine fits of 24-hour
      data of corneal hysteresis did not display a 24-hour rhythm. CONCLUSIONS: In
      healthy young adults, CCT was thicker, and IOP was higher during the nocturnal
      period than during the diurnal period. Nocturnal peak CCT occurred a few hours
      earlier than did nocturnal peak IOP. The twenty-four-hour change in corneal
      viscoelasticity was not significant. There was no evidence that the 24-hour
      change in IOP was due to the change in corneal biomechanical properties.

PMID- 17003436
TI  - Transduction of TAT fusion proteins into the human and bovine trabecular
      meshwork.
AB  - PURPOSE: To examine the applicability of TAT (the protein transduction domain of
      transactivating transcription polypeptide)-mediated protein-transduction
      technology, in introducing proteins of interest into trabecular meshwork (TM)
      cells in various culture systems. METHODS: Normal human TM cell cultures, human
      tissues in organ cultures, and bovine eyes in perfusion organ cultures were
      incubated or perfused for various lengths of time with TAT- and hemagglutinin
      (HA)-tagged fusion proteins, TAT-HA-beta-galactosidase (TAT-HA-beta-gal), TAT-HA
      myocilin, and TAT-HA-myocilin-EGFP. Transduction of TAT-HA-beta-gal was detected
      by X-gal staining. Transduction of myocilin or myocilin-EGFP was evaluated by
      immunostaining or fluorescence. beta-Gal and EGFP proteins were used as the
      negative control. RESULTS: Blue X-gal staining, signifying beta-gal activity
      resulting from transduction, was observed in cultured TM cells in a concentration
      and time-dependent manner. TAT-HA-beta-gal was also transduced into cells in all
      regions of TM tissues in organ cultures. TM cell cultures, after TAT-HA-myocilin
      incubation, showed an enhanced myocilin staining compared with the control
      cultures. Stronger myocilin or HA staining was also noted in TM tissues of TAT-HA
      myocilin-incubated or -perfused eyes. Myocilin transduction resulted in a loss of
      actin stress fibers and focal adhesions in TM cells in culture. The level of
      phosphorylated myosin light chain was reduced. Human and bovine TM tissues after
      TAT-myocilin transduction also exhibited a diminished actin and paxillin-vinculin
      staining. CONCLUSIONS: TAT fusion proteins can be efficiently transduced into TM
      cells and tissues. The TAT-mediated protein transduction technology may be
      valuable in studies of proteins such as myocilin in the TM.

PMID- 17003437
TI  - Osteopontin is proinflammatory in experimental autoimmune uveitis.
AB  - PURPOSE: Osteopontin (OPN) has been implicated in inflammatory and wound-healing
      processes. Increased OPN mRNA levels have been reported in experimental
      autoimmune uveitis (EAU), but the function of OPN in the inflamed eye is unknown.
      The purpose of this study was to investigate the role of OPN in the pathogenesis
      of EAU. METHODS: EAU was induced in OPN-null and wild-type (WT) mice by
      immunization with interphotoreceptor retinoid-binding protein (IRBP).
      Immunofluorescence experiments were performed to identify OPN-positive cells in
      WT mice. Disease incidence, serum IRBP antibody levels, vitreous infiltrates,
      retinal granulomas, and lymphocyte proliferation were assessed in OPN-null and WT
      mice. To determine whether OPN could induce an EAU-like condition, purified OPN
      and OPN fragments were injected intraocularly into WT mice and vitreous
      infiltrates were characterized and quantified. RESULTS: In WT EAU-positive eyes,
      cell types with increased OPN immunoreactivity were identified as F4/80-positive
      macrophages/microglia and CD4-positive T cells. OPN-null mice manifested
      attenuated disease with decreased vitreous infiltrates, fewer granulomas, less
      lymphocyte proliferation, and lower serum IRBP antibody levels. Exogenous full
      length OPN, as well as N- and C-terminal fragments, induced leukocyte
      infiltration and retinal folding, with some similarities to EAU. CONCLUSIONS: The
      results demonstrate that OPN is proinflammatory in EAU and may be important for
      recruitment and activation of leukocytes in retinal inflammation.

PMID- 17003438
TI  - CD4+PD-1+ T cells acting as regulatory cells during the induction of anterior
      chamber-associated immune deviation.
AB  - PURPOSE: To study the expression and functional characteristics of programmed
      death-1 (PD-1) and its ligands in the spleens of mice undergoing anterior chamber
      associated immune deviation (ACAID). METHODS: ACAID was induced in BALB/c mice by
      intracameral injection of ovalbumin (OVA). The expression of PD-1 and its ligands
      in the spleens of ACAID mice was determined by quantitative real-time PCR,
      Western blotting, and flow cytometry. In vitro proliferation assays, enzyme
      linked immunosorbent assays, and adoptive transfer assays were used to
      investigate the functional characteristics of splenic CD4+PD-1+ T cells of ACAID
      mice. RESULTS: Both mRNA and protein of PD-1, PD-L1, and PD-L2 were markedly
      upregulated in the spleens of ACAID mice compared with controls. CD4+PD-1+ T
      cells from ACAID mice produced large amounts of IL-10 and exhibited in vitro
      antigen-specific suppressive activity. CD4+PD-1+ T cells from ACAID mice were
      able to significantly inhibit the antigen-specific, delayed-type hypersensitivity
      response when adoptively transferred to naive mice. CONCLUSIONS: CD4+PD-1+ T
      cells from ACAID mice, as regulatory cells, are involved in the induction of
      antigen-specific suppression in association with enhanced expression of IL-10.
      CD4+PD-1+ T cells in the murine spleen may represent a substantial population of
      regulatory T cells possibly responsible for the induction of ACAID after
      intracameral injection of antigen.

PMID- 17003439
TI  - Salicylic acid reduces the production of several potential virulence factors of
      Pseudomonas aeruginosa associated with microbial keratitis.
AB  - PURPOSE: Pseudomonas aeruginosa is a common cause of contact-lens-related
      microbial keratitis. This bacterium is becoming increasingly resistant to
      antibiotics, and even if the infection can be treated with antibiotics, damage to
      the cornea resulting from the combined effect of bacteria and host factors can
      lead to loss of vision. The purpose of this study was to test the effect of
      salicylic acid on the production of potential virulence factors during the growth
      of P. aeruginosa. METHODS: Bacterial cells were grown in a subinhibitory
      concentration of salicylic acid, and supernatants were collected and analyzed for
      presence of proteases by using zymography and hydrolysis of chromogenic
      substrates. The supernatants were also analyzed for the amount of acetylated
      homoserine lactones by using bacterial reporter strains. Pseudomonas cells from
      salicylic acid cultures were analyzed for their twitching and swimming motility
      as well as their ability to invade or cause the death of corneal epithelial
      cells. RESULTS: Growth in a subinhibitory concentration of salicylic acid
      resulted in a significant reduction in the number of bacterial cells and a
      reduction in the rate of the number of bacteria increasing during logarithmic
      growth, but the time to reach the stationary phase of growth was unchanged. These
      changes in growth pattern affected the amount of acylated homoserine lactones
      produced by P. aeruginosa 6294. Also affected by growth in salicylic acid was the
      ability of strain 6294 to show twitching or swimming motility. Salicylic acid
      also reduced the invasion of strain 6294 into corneal epithelial cells and the
      epithelial cell death caused by strain 6206. Furthermore, production of proteases
      by P. aeruginosa was significantly reduced by growth in salicylic acid.
      CONCLUSIONS: The results of this study clearly demonstrate that salicylic acid
      has a significant impact on several potential virulence factors of P. aeruginosa
      that may be involved in the production of microbial keratitis. These effects were
      probably mediated by reduction in the cell density and concomitant reduction in
      the quorum-sensing signaling molecules, the acylated homoserine lactones,
      produced by P. aeruginosa.

PMID- 17003440
TI  - Role of swarming migration in the pathogenesis of bacillus endophthalmitis.
AB  - PURPOSE: Bacillus cereus causes one of the most rapidly blinding forms of
      bacterial endophthalmitis. Migration of B. cereus throughout the eye during
      endophthalmitis is a unique aspect of this disease that may contribute to
      intraocular virulence. This study was conducted to analyze the contribution of
      swarming and intraocular migration to the pathogenesis of experimental
      endophthalmitis. METHODS: Eyes were injected intravitreally with 100 colony
      forming units (CFU) of either wild-type, nonswarming, or swarming-complemented
      strains of B. cereus. Pathogenicity was compared throughout the course of
      infection by biomicroscopy, histology, electroretinography, and bacterial and
      inflammatory cell quantitation. RESULTS: Wild-type, nonswarming, and swarming
      complemented B. cereus strains grew to a similar number in the vitreous
      throughout the course of infection. Unlike the wild-type and swarming
      complemented strains, the nonswarming mutant did not migrate to the anterior
      segment during infection. The rate of decrease in retinal responses of eyes
      infected with the all strains was similar, resulting in near complete elimination
      of retinal function by 12 hours. All Bacillus strains caused similar degrees of
      posterior segment inflammation and retinal destruction. However, the accumulation
      of inflammatory cells in the anterior chamber, hyphemae, and corneal ring
      abscesses did not occur in eyes infected with the nonswarming mutant.
      CONCLUSIONS: The deficiency in swarming had little effect on retinal function
      loss or the overall course or severity of experimental B. cereus endophthalmitis.
      However, a deficiency in swarming prevented Bacillus from migrating to the
      anterior segment, leading to less severe anterior segment disease.

PMID- 17003441
TI  - Microsporidial keratitis in India: 16S rRNA gene-based PCR assay for diagnosis
      and species identification of microsporidia in clinical samples.
AB  - PURPOSE: To evaluate 16S rRNA-based polymerase chain reactions for the detection
      and species identification of the microsporidia that cause keratitis. METHODS: Of
      the 5892 cases of microbial keratitis seen between September 2002 and December
      2005, 31 (0.5%) microscopically diagnosed cases of microsporidial keratitis were
      included in the test group; 103 patients with nonmicrosporidial keratitis
      constituted the control group. A 16S rRNA-based pan-microsporidian PCR was chosen
      for the detection of microsporidian DNA. Species level identification was made
      using species-specific primer sets of Encephalitozoon spp (E. cuniculi, E.
      hellem, and E. intestinalis). Sequencing and BLAST analysis of amplicons obtained
      with pan-microsporidian primers were performed for validation. RESULTS: The
      corneal scrapings from 26 of 31 cases in the test group and 2 of 103 cases in the
      control group showed a 250- to 280-bp amplicon in PCR by pan-microsporidian
      primers (sensitivity of 83% and specificity of 98%). The amplicons of 13 of 26
      test group samples were identified by species-specific PCR: E. cuniculi, n = 7
      (549 bp); E. hellem; n = 3 (549 bp); E. intestinalis; n = 1 (520 bp). The two
      cases in the control group were identified to be E. cuniculi. The remaining 15
      cases (test group) were confirmed to be Vittaforma corneae by sequencing and
      BLAST analysis. All species were confirmed by sequencing and database homology
      comparison. CONCLUSIONS: This study is the first to validate PCR-based assays for
      detection of microsporidial DNA in corneal scrapings. Pan microsporidian PCR can
      be a useful adjunct with smear examination in the diagnosis of microsporidial
      keratitis.

PMID- 17003442
TI  - Functional characterization of a naturally occurring Cx50 truncation.
AB  - PURPOSE: Lens connexins undergo proteolytic cleavage of their C termini during
      fiber maturation. Although the functional significance of this is unknown,
      cleavage has been correlated with changes in channel-gating properties. This
      study evaluates the functional consequences of this endogenous truncation by
      characterizing the properties of a C-terminal truncated Cx50 protein. METHODS:
      Murine and human Cx50 were truncated at amino acids 290 and 294, respectively,
      before expression in paired Xenopus oocytes or mammalian cells. Protein
      expression was evaluated by immunocytochemistry. Dual whole-cell voltage clamp
      techniques were used to analyze macroscopic and single-channel conductance,
      voltage-gating properties, and kinetics; pH gating sensitivity was measured by
      superfusion with 100% CO2-saturated media. RESULTS: Cx50tr290 channels exhibited
      an 86% to 89% reduction in mean macroscopic conductance compared with full-length
      Cx50. Heterotypic channels formed functional gap junctions, displayed an
      intermediate level of coupling, and exhibited unaltered voltage-gating
      properties. C-terminal truncation did not alter single-channel gating
      characteristics or unitary conductance. Interestingly, truncated and full-length
      Cx50 channel conductances were reversibly blocked by cytoplasmic acidification.
      CONCLUSIONS: C-terminal truncation of Cx50 did not inhibit the formation of
      homotypic or heterotypic channels. However, a significant decrease in conductance
      was observed for truncated channels, a phenomenon independent of alterations in
      voltage-gating sensitivity, kinetics, or chemical gating. These results provide a
      plausible explanation for the 50% decrease in junctional coupling observed during
      lens fiber maturation.

PMID- 17003444
TI  - Phosphatidylinositol 3-kinase is necessary for lens fiber cell differentiation
      and survival.
AB  - PURPOSE: To determine the mechanisms of action of phosphatidylinositol 3-kinase
      (PI3K) in lens cell differentiation and survival. METHODS: Primary quail lens
      cell cultures were treated at different stages of differentiation with the PI3K
      inhibitor LY294002, and expression of survival proteins and differentiation
      markers were determined by immunoblot analysis. The connection between PI3K
      regulation of lens differentiation and actin cytoskeleton reorganization was
      examined by fluorescent-phalloidin staining and Rac activity assay. Survival in
      the absence of PI3K signaling was examined by TUNEL and DAPI staining.
      Phosphorylation of the PI3K effector glycogen synthase kinase-3 (GSK3) in the
      absence of PI3K signaling was induced with lithium chloride. RESULTS: Exposure to
      LY294002 blocked lens epithelial cell differentiation initiation. This result was
      linked to attenuation of Rac activity and inhibition of actin filament
      reorganization from stress fibers to cortical fibers, which has been shown to
      signal lens differentiation initiation. The survival of lens epithelial cells in
      the absence of PI3K signaling correlated with induction of numerous survival
      factors, including Bcl-2. In contrast, inhibition of PI3K signaling in
      differentiating lens fiber cells induced apoptosis by blocking inactivation of
      GSK3, showing that PI3K/GSK3 signaling has a protective role in the late stages
      of differentiation as nuclei and organelles are lost. CONCLUSIONS: PI3K signaling
      regulates lens cell differentiation initiation through its ability to signal
      reorganization of the actin cytoskeleton from stress fibers to cortical fibers.
      In differentiating lens fiber cells, PI3K has a protective function, signaling
      survival through inactivation of its downstream effector GSK3.

PMID- 17003443
TI  - Suppression of human lens epithelial cell proliferation by proteasome inhibition,
      a potential defense against posterior capsular opacification.
AB  - PURPOSE: Posterior capsular opacification (PCO) is caused by the proliferation,
      migration, and epithelial-mesenchymal transition (EMT) of the remaining lens
      epithelial cells (LECs) after cataract surgery. Studies have shown that
      proteasome inhibition interferes with EMT and remodeling of the extracellular
      matrix. This study was conducted to investigate suppression of LEC proliferation
      by proteasome inhibition and its signaling pathway. METHODS: HLE B-3 cells and
      human lens epithelium explants from 17- to 20-week fetal lenses were cultured and
      treated with TGF-beta2 (1 or 10 ng/mL), FGF-2 (20 or 50 ng/mL), HGF (10 ng/mL)
      and 5 or 10 muM MG132. LEC proliferation was determined using both the WST-1
      reagent and proliferating cell nuclear antigen (PCNA) expression. Protein
      expression was observed by Western blot analysis. Transfection with p21/p27 siRNA
      was performed to evaluate the mechanism of the antiproliferative effect of
      proteasome inhibition. RESULTS: TGF-beta2 suppressed proliferation of HLE B-3
      cells, whereas FGF-2 and HGF enhanced proliferation. Proliferation suppression by
      TGF-beta2 was blocked by adding FGF-2 or HGF. Proteasome inhibitor (MG132)
      treatment strongly inhibited the proliferation of LECs, either alone or in the
      presence of TGF-beta2, FGF-2, or HGF. These findings were confirmed by observing
      PCNA expression. Similar results were obtained with primary human LECs.
      Expression of cell cycle regulatory proteins was determined to evaluate the
      mechanism of the antiproliferative activity of proteasome inhibition. MG132
      caused a significant increase in p21 and p27 protein and decrease in CDK2, but no
      change in p53, p57, CDK4, or CDK6 protein. The antiproliferative effect of MG132
      was significantly reversed in samples transfected with p21 and p27 siRNA, which
      reduced p21 and p27 protein expression to very low levels that remained below
      basal control levels, even after treatment with MG132. CONCLUSIONS: Proteasome
      inhibition decreases the proliferation of LECs in the presence or absence of TGF
      beta2, FGF-2, and HGF. This process is mediated in part by an increase in p21 and
      p27 proteins. These findings suggest that proteasome inhibitors are good
      candidates for blocking development of PCO.

PMID- 17003445
TI  - Dual roles of diadenosine polyphosphates in corneal epithelial cell migration.
AB  - PURPOSE: To investigate the influence of diadenosine polyphosphates on the rate
      of corneal epithelial cell migration. METHODS: Primary corneal epithelial cell
      cultures were obtained from New Zealand White rabbits. Immunocytochemical
      experiments were performed by fixing the cells with 4% paraformaldehyde (PFA) and
      incubated with cytokeratin 3 primary antibody, which was subsequently incubated
      with a secondary IgG mouse labeled with FITC, and the cells were observed under
      confocal microscopy. Migration studies were performed by taking confluent
      monolayers that were wounded with a pipette tip and challenged with different di-
      and mononucleotides with or without P2 antagonist (n = 8 each treatment). For
      concentration-response analysis, compounds were tested in doses ranging from 10(
      8) to 10(-3) M (n = 8). The stability of the dinucleotides was assayed by HPLC,
      with an isocratic method (n = 4). RESULTS: Cells under study were verified as
      corneal epithelial cells via the immunocytochemical analysis. Cell migration
      experiments showed that Ap4A, UTP, and ATP accelerated the rate of healing (5,
      2.75, and 3 hours, respectively; P < 0.05; P < 0.001), whereas Ap3A, Ap5A, and
      UDP delayed it (6.5, 10, and 2 hours, respectively; P < 0.05). ADP did not modify
      the rate of migration. Antagonists demonstrated that Ap4A and Ap3A did activate
      different P2Y receptors mediating corneal wound-healing acceleration and delay.
      Concerning the possible degradation of the dinucleotides, it was almost
      impossible to detect any products resulting from their cleavage. CONCLUSIONS:
      Based on the pharmacological profile of all the compounds tested, the two main
      P2Y receptors that exist in these corneal cells are a P2Y(2) receptor
      accelerating the rate of healing and a P2Y6 receptor that delays this process.

PMID- 17003446
TI  - Uveal melanocytes do not respond to or express receptors for alpha-melanocyte
      stimulating hormone.
AB  - PURPOSE: Whereas cutaneous pigmentation increases after exposure to ultraviolet
      (UV) irradiation, ocular pigmentation does not. This study was designed to
      examine the evidence that alpha-melanocyte-stimulating hormone (alpha-MSH), which
      is thought to be the mediator of UV response in the skin, has any role to play in
      uveal melanocytes. METHODS: Human uveal melanocytes derived from the choroid and
      the iris were cultivated by using eyes harvested from adult cadaveric donors and
      were assessed by Northern blot analysis for growth and melanogenic response to
      alpha-MSH and expression of the receptor for alpha-MSH (MC1-R). In addition,
      expression of alpha-MSH was evaluated in ocular tissue by immunocytochemistry.
      RESULTS: Uveal melanocytes, unlike cutaneous melanocytes in vitro, exhibited no
      stimulation of proliferation in response to alpha-MSH at dosages ranging from 0.1
      to 100 muM. In addition, tyrosine hydroxylase, DOPA oxidase, and protein levels
      for tyrosinase, TRP-1, and TRP-2 were not influenced by alpha-MSH. Associated
      with the lack of alpha-MSH response in cultured uveal melanocytes was the absence
      of expression of the receptor for alpha-MSH (MC1-R), as assessed by Northern blot
      analysis. Also in contrast to the skin, pigmented ocular tissue lacked expression
      of the alpha-MSH ligand, as assessed by immunocytochemistry. CONCLUSIONS: In
      conclusion, ocular pigmentation does not appear to be regulated by melanocyte
      stimulating hormone.

PMID- 17003448
TI  - The Zebrafish fade out mutant: a novel genetic model for Hermansky-Pudlak
      syndrome.
AB  - PURPOSE: To characterize retinal morphology and visual system function in the
      zebrafish mutant fade out (fad) and to establish the mutant as a lower vertebrate
      model for Hermansky-Pudlak syndrome (HPS). METHODS: Retinal morphology of fad
      larvae was examined between 3 and 9 days postfertilization (dpf) by standard
      histology, transmission electron microscopy, and immunohistochemistry
      examination. Apoptotic cells were visualized by TdT-mediated dUTP nick-end
      labeling (TUNEL) staining. Visual system function was probed by
      electroretinography and behavioral assessment by optokinetic response
      measurements. Blood clotting was evaluated by time to occlusion testing of blood
      vessels as an arterial thrombosis assay. The chromosomal location of fad was
      determined by simple sequence-length polymorphism mapping. Genomic fragments of
      candidate genes were cloned by standard molecular techniques and mapped to the
      zebrafish genome by radiation hybrid mapping. RESULTS: Mutant fad larvae are
      hypopigmented and show structural defects in the outer retina. Melanosomes of
      these larvae in the retinal pigment epithelium are hypopigmented, generally
      smaller, and progressively reduced in number compared to nonmutant larvae.
      Progressive microvilli protrusions into the photoreceptor cell layer are not
      detectable, and photoreceptor outer segments get shorter and are misaligned.
      Photoreceptors subsequently undergo apoptosis, with a peak of cell death at 6
      dpf. Electrical responses of the retina and visual performance are severely
      reduced. Blood clotting is prolonged in mutant fad larvae. Genomic mapping of fad
      reveals distinct genomic positions of the mutant gene from known human HPS genes.
      CONCLUSIONS: The fad mutant shows syndromic defects in pigmentation, outer
      retinal structure and function, and blood clotting. This syndrome is
      characteristic of Hermansky-Pudlak syndrome (HPS), making fad a novel genetic
      model of HPS. The gene does not cosegregate with the known human HPS genes,
      suggesting a novel molecular cause of HPS.

PMID- 17003447
TI  - Bovine and porcine transscleral solute transport: influence of lipophilicity and
      the Choroid-Bruch's layer.
AB  - PURPOSE: To determine the influence of the choroid-Bruch's layer and solute
      lipophilicity on in vitro transscleral drug permeability in bovine and porcine
      eyes. METHODS: The in vitro permeability of two VEGF inhibitory drugs, budesonide
      and celecoxib, which are lipophilic and neutral at physiologic pH, and of three
      marker solutes, 3H-mannitol (hydrophilic, neutral), sodium fluorescein
      (hydrophilic, anionic), and rhodamine 6G (lipophilic, cationic), were determined
      across freshly excised scleras, with or without the underlying choroid-Bruch's
      layer. Select studies were performed using porcine sclera with and without
      choroid-Bruch's layer. Neural retina was removed by exposure of the eyecup to
      isotonic buffer and wherever required, the retinal pigment epithelial (RPE) layer
      of the preparation was disrupted and removed by exposure to hypertonic buffer.
      Because of the poor solubility of celecoxib and budesonide, permeability studies
      were conducted with 5% wt/vol of hydroxypropyl-beta-cyclodextrin (HPbetaCD). For
      other solutes, permeability studies were conducted, with and without HPbetaCD.
      Partitioning of the solutes into bovine sclera and choroid-Bruch's layer was also
      determined. RESULTS: The calculated log (distribution coefficient) values were 
      2.89, -0.68, 2.18, 3.12, and 4.02 for mannitol, sodium fluorescein, budesonide,
      celecoxib, and rhodamine 6G, respectively. Removal of RPE was confirmed by
      transmission electron microscopy and differences in the transport of mannitol.
      The order of the permeability coefficients (Papp) across sclera and sclera
      choroid-Bruch's layers in bovine and porcine models was 3H-mannitol > fluorescein
      > budesonide > celecoxib > rhodamine 6G, with HPbetaCD, and 3H-mannitol >
      fluorescein > rhodamine 6G, without HPbetaCD. The presence of choroid-Bruch's
      layer reduced the bovine scleral permeability by 2-, 8-, 16-, 36-, and 50-fold
      and porcine tissue permeability by 2-, 7-, 15-, 33-, and 40-fold, respectively,
      for mannitol, sodium fluorescein, budesonide, celecoxib, and rhodamine 6G. The
      partition coefficients measured in bovine tissues correlated positively with the
      log (distribution coefficient) and exhibited a trend opposite that of transport.
      The partition coefficient ratio of bovine choroid-Bruch's layer to sclera was
      approximately 1, 1.5, 1.7, 2, and 3.5, respectively, for the solutes, as listed
      earlier. CONCLUSIONS: The choroid-Bruch's layer is a more significant barrier to
      drug transport than is sclera. It hinders the transport of lipophilic solutes,
      especially a cationic solute, more than hydrophilic solutes and in a more
      dramatic way than does sclera. The reduction in transport across this layer
      directly correlates with solute binding to the tissue. Understanding the
      permeability properties of sclera and underlying layers would be beneficial in
      designing better drugs for transscleral delivery.

PMID- 17003449
TI  - Delivery from episcleral exoplants.
AB  - PURPOSE: To assess the impact of an episcleral exoplant on transscleral delivery.
      METHODS: New Zealand White rabbits were given a periocular injection of sodium
      fluorescein (fluorescein, 376 Da) or an episcleral exoplant loaded with
      fluorescein. Two types of exoplants were tested: (1) a rigid polyethylene device,
      impermeable on one side and open to the sclera on the other, that contained
      compressed pellets of fluorescein and was sutured loosely (apposition group) or
      tightly to indent the sclera (indentation group) and (2) flexible refillable
      silicone exoplants also open to the sclera that were secured by suturing, to form
      a sealed episcleral chamber that was filled with a fluorescein solution. Ocular
      and plasma fluorophotometry were performed at several time points, and histology
      was performed to evaluate the effect of exoplants on the periocular tissue.
      RESULTS: Within 20 minutes of a periocular injection of fluorescein, peak
      fluorescence was visible in the anterior chamber (AC) and at later time points
      was displaced toward the retina; at all time points, the highest fluorescence was
      in the AC. For the polyethylene device indentation group, peak fluorescence was
      in the retina and posterior vitreous and spread to the AC over time. For the
      apposition exoplant group, two peaks of fluorescence were seen initially, one in
      the retina and posterior vitreous and one in the AC. The area under the
      concentration time curve (AUC +/- SE) for fluorescein concentration was 144.4 +/-
      15.1 mug . h/mL for the retinal peak and 43.6 +/- 7.1 mug . h/mL for the
      posterior vitreous peak after injection of 5 mg of fluorescein into a silicone
      exoplant, compared with a retinal peak of 3.9 +/- 0.3 and a posterior vitreous
      peak of 0.99 +/- 0.26 mug . h/mL after periocular injection of 5 mg of
      fluorescein (P < 0.01 for each). Peak plasma fluorescein levels were
      significantly reduced in the exoplant group compared with periocular injection.
      CONCLUSIONS: An episcleral exoplant facilitates diffusion of fluorescein through
      the sclera resulting in high levels in the retina and posterior vitreous; levels
      are markedly increased compared with periocular injection of the same amount of
      fluorescein. It also reduces peak plasma levels indicating reduction of systemic
      absorption. This procedure provides a new approach that can be combined with
      sustained-release preparations to optimize delivery of agents to the retina and
      choroid while minimizing the potential for systemic toxicity.

PMID- 17003450
TI  - Improvement in rod and cone function in mouse model of Fundus albipunctatus after
      pharmacologic treatment with 9-cis-retinal.
AB  - PURPOSE: To assess changes in rod and cone visual functions in a mouse model of
      Fundus albipunctatus with disrupted 11-cis-retinol dehydrogenase (RDH) genes
      after pharmacologic treatment with an artificial retinal chromophore. METHODS:
      Retinoid levels and photoreceptor functions of Rdh5-/-Rdh11-/- mice at a variety
      of light intensities were analyzed with normal-phase HPLC and ERG techniques.
      Production of 11-cis-retinal, the visual pigment chromophore, was suppressed with
      a potent inhibitor of the retinoid cycle, all-trans-retinylamine (Ret-NH2). The
      chromophore was replaced by a functional geometric isomer, 9-cis-retinal,
      delivered by oral gavage. RESULTS: Aberrant cone responses were detected in 12
      month-old Rdh5-/-Rdh11-/- mice raised in a 12-hour light/12-hour dark cycle. This
      cone defect was exacerbated in conditions of low levels of 11-cis-retinal.
      Administration of 9-cis-retinal increased the rate of dark adaptation and
      improved cone function in Rdh5-/-Rdh11-/- mice. CONCLUSIONS: Disruption of 11-cis
      RDHs causes a slowly developing cone dystrophy caused by inefficient cone pigment
      regeneration. Rod and cone visual function improved significantly in the mouse
      model of F. albipunctatus after treatment with 9-cis-retinal, suggesting a
      potential approach to slow the progression of cone dystrophy in affected humans.

PMID- 17003451
TI  - Effects of peroxisome proliferator-activated receptor gamma and its ligand on
      blood-retinal barrier in a streptozotocin-induced diabetic model.
AB  - PURPOSE: To clarify whether endogenous peroxisome proliferator-activated receptor
      gamma (PPARgamma) and its ligand, rosiglitazone, affect retinal leukostasis and
      the associated vascular leakage using an experimental diabetic model. METHODS:
      Diabetes was induced in heterozygous PPARgamma+/- mice and Brown Norway rats with
      an intraperitoneal streptozotocin (STZ) injection. Retinal leukostasis and
      leakage, quantified by concanavalin A (Con A) lectin perfusion labeling combined
      with a fluorophotometric dextran leakage assay, were investigated at 120 days in
      diabetic PPARgamma+/- and wild-type mice and at 21 days in diabetic rats
      receiving rosiglitazone or the vehicle. The retinal protein expression levels of
      vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, and
      the intercellular adhesion molecule (ICAM)-1 were investigated by means of the
      ELISA assay. RESULTS: In the diabetic PPARgamma+/- mice, retinal leukostasis and
      leakage were greater than in the diabetic wild-type mice. In addition retinal
      leukostasis and leakage were suppressed by treatment with rosiglitazone in
      experimental diabetic rats. ELISA analysis revealed that the upregulated ICAM-1
      expression in the diabetic rat retina was reduced by rosiglitazone treatment.
      CONCLUSIONS: An endogenous pathway involving PPARgamma provides protection
      against retinal leukostasis and retinal leakage in diabetes and treatment with
      PPARgamma specific ligands inhibits retinal leukostasis and retinal leakage in
      diabetic rats.

PMID- 17003452
TI  - Two-photon-excited fluorescence imaging of human RPE cells with a femtosecond
      Ti:Sapphire laser.
AB  - PURPOSE: To record the distribution and spectrum of human retinal pigment
      epithelial cell lipofuscin (LF) by two-photon-excited fluorescence (TPEF) and
      confocal laser scanning microscopy. METHODS: Ex vivo TPEF imaging of the human
      retinal pigment epithelium (RPE) of human donor eyes was conducted with a
      multiphoton laser scanning microscope that employs a femtosecond Ti:sapphire
      laser as an excitation laser source. The spectrum of autofluorescence of LF
      granules was analyzed with a confocal laser scanning microscope coupled to a UV
      argon laser. RESULTS: TPEF examination allowed for imaging of RPE cell morphology
      and intracellular distribution of LF granules with high-contrast and
      submicrometer resolution. Variations in cell size and shape as well as in
      autofluorescence spectra of individual LF granules were recorded. The typical
      diameter of LF granules was found to be below 1 mum, with some RPE cells
      possessing larger granules. Remarkably, enhanced blue-green autofluorescence was
      observed from these larger LF granules. CONCLUSIONS: TPEF imaging represents a
      novel tool for the investigation of morphologic and spectral characteristics of
      human RPE cells. Spectral variations of individual LF granules may indicate
      differences in the complex molecular composition. Compared to conventional single
      photon excited autofluorescence, TPEF with a tunable laser source allows for
      reduced photo damage and deeper sensing depth. It may help to elucidate further
      the pathophysiological role of LF accumulation as a common downstream
      pathogenetic pathway in retinal diseases. With the proof of principle from this
      ex vivo study, further work is now planned to evaluate the safety of TPEF RPE
      imaging in RPE cultures and animal models.

PMID- 17003453
TI  - Elovl4 5-bp-deletion knock-in mice develop progressive photoreceptor
      degeneration.
AB  - PURPOSE: To develop and characterize a heterozygous knock-in mouse model carrying
      the 5-bp deletion in Elovl4 (E_mut+/-) and to study the pathology underlying
      Stargardt-like macular degeneration (STGD3). METHODS: E_mut+/- mice were
      generated by targeting a 5-bp deletion (AACTT) in the Elovl4 gene by homologous
      recombination. E_mut+/- mice of age 2 to 18 months and age-matched wild-type (Wt)
      littermate control animals were analyzed for the expression of Elovl4 transcript,
      ELOVL4 protein, photoreceptor-specific genes, and retinal fatty acid composition.
      Functional retinal changes were evaluated by electroretinography (ERG) and by
      morphologic and ultrastructural criteria. RESULTS: E_mut+/- mice retinas showed
      the presence of both Wt and mutant Elovl4 transcripts and proteins. Morphologic
      evaluation revealed cone photoreceptor ultrastructural abnormalities as early as
      2 months of age, accumulation of lipofuscin in retinal pigment epithelium (RPE),
      and subretinal deposits at later ages. Shortening of rod outer segments (OS) was
      observed at approximately 10 months of age. Both cone and rod changes progressed
      with age. Unlike rod-specific genes, expression of selected cone specific genes
      was significantly reduced by 7 months of age. Mixed rod-cone and light-adapted b
      waves were higher than normal at both 8 and 15 months. Levels of the fatty acids
      20:5 (P = 0.027), 22:5 (P = 0.040) and 24:6 (P = 0.005) were found to be
      significantly lower in the retinas of E_mut+/- mice than in retinas of control
      subjects. CONCLUSIONS: E_mut+/- animals display characteristic features
      associated with Stargardt-like macular degeneration and serve as a model for the
      study of the mechanism underlying STGD3.

PMID- 17003454
TI  - Intravitreal bevacizumab for choroidal neovascularization caused by AMD (IBeNA
      Study): results of a phase 1 dose-escalation study.
AB  - PURPOSE: To evaluate the safety of three dose regimens of intravitreal
      bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) for the
      management of choroidal neovascularization (CNV) associated with age-related
      macular degeneration (AMD). METHODS: This was a prospective, nonrandomized open
      label study of 45 patients with AMD and subfoveal CNV. A standardized ophthalmic
      evaluation was performed at baseline and at weeks 1, 6, and 12 (+/-1) after a
      single intravitreous injection (1.0, 1.5, or 2.0 mg) of bevacizumab. Main
      outcomes measures include clinical evidence of toxicity and complications.
      Changes in best corrected visual acuity (BCVA) and lesion characteristics-macular
      morphology were also evaluated. RESULTS: The most common adverse events were
      conjunctival hyperemia and subconjunctival hemorrhage at the injection site. Mean
      BCVA improved from baseline throughout the study (P < 0.001; ANOVA with Geisser
      Greenhouse correction). Compared with baseline, BCVA was improved at week 1 (P =
      0.001), week 6 (P < 0.001), and week 12 (P = 0.001; Dunnett test). At week 12,
      the lesion area and CNV area were stable or decreased in 79.1% (34/43) and in
      74.4% (32/43) of patients, respectively, with no deterioration of macular
      architecture observed in 83.7% (36/43). A dose-related change in BCVA (in Early
      Treatment Diabetic Retinopathy Study [ETDRS] lines) was observed at week 12 (1.0
      mg [+0.3 line]; 1.5 mg [+0.6 line]; and 2.0 mg [+1.0 line]; P = 0.02;
      nonparametric test for ordered groups). CONCLUSIONS: A single intravitreal
      bevacizumab injection was well tolerated and, except for minor transient local
      adverse events, no other adverse events were observed. In the short-term,
      treatment was associated with vision stabilization or improvement and no
      unfavorable neovascular lesion-macular changes in most patients.

PMID- 17003455
TI  - Genomic rearrangements of the PRPF31 gene account for 2.5% of autosomal dominant
      retinitis pigmentosa.
AB  - PURPOSE: To determine whether genomic rearrangements in the PRPF31 (RP11) gene
      are a frequent cause of autosomal dominant retinitis pigmentosa (adRP) in a
      cohort of patients with adRP. METHODS: In a cohort of 200 families with adRP,
      disease-causing mutations have previously been identified in 107 families. To
      determine the cause of disease in the remaining families, linkage testing was
      performed with markers for 13 known adRP loci. In a large American family,
      evidence was found of linkage to the PRPF31 gene, although DNA sequencing
      revealed no mutations. SNP testing throughout the genomic region was used to
      determine whether any part of the gene was deleted. Aberrant segregation of a SNP
      near exon 1 was observed, leading to the testing of additional SNPs in the
      region. After identifying an insertion-deletion mutation, the remaining 92
      families were screened for genomic rearrangements in PRPF31 with multiplex
      ligation-dependent probe amplification (MLPA). RESULTS: Five unique
      rearrangements were identified in the 93 families tested. In the large family
      used for linkage exclusion testing, an insertion-deletion was found that disrupts
      exon 1. The other four mutations identified in the cohort were deletions, ranging
      from 5 kb to greater than 45 kb. Two of the large deletions encompass all PRPF31
      as well as several adjacent genes. The two smaller deletions involve either 5 or
      10 completely deleted exons. CONCLUSIONS: In an earlier long-term study of 200
      families with adRP, disease-causing mutations were identified in 53% of the
      families. Mutation-testing by sequencing missed large-scale genomic
      rearrangements such as insertions or deletions. MLPA was used to identify genomic
      rearrangements in PRPF31 in five families, suggesting a frequency of
      approximately 2.5%. Mutations in PRPF31 now account for 8% of this adRP cohort.

PMID- 17003457
TI  - Oxidant-mediated Akt activation in human RPE cells.
AB  - PURPOSE: To determine whether a model oxidant, hydrogen peroxide (H2O2),
      influences Akt activation and, if so, whether Akt activation promotes retinal
      pigment epithelial (RPE) cell survival. METHODS: Cultured human RPE cells were
      pretreated with medium alone, with LY294002 (LY), an inhibitor of
      phosphatidylinositol-3 kinase (PI3K) and its downstream effector Akt, or with
      Akt/protein kinase B signaling inhibitor (API)-2, a specific Akt inhibitor, and
      then were stimulated with H2O2 at different doses for various times. Akt
      phosphorylation was evaluated by Western blot using antibody against
      phosphorylated Akt (Ser473). The effect of Akt blockade on RPE cell viability was
      assessed by tetrazolium salt (WST-1) assay and a lactate dehydrognease (LDH)
      release assay. Caspase-mediated cytokeratin cleavage, an early apoptosis marker,
      was assessed by M30 antibody staining. Caspase-independent apoptosis was
      determined by nuclear translocation of apoptosis-inducing factor (AIF). RPE cell
      morphology was evaluated by electron microscopy. The effect of H2O2 on downstream
      Akt targets was examined by Western blot using antibody against phosphorylated
      forkhead in rhabdomyosarcoma (FKHR) and phosphorylated glycogen synthase kinase
      (GSK)-3beta. RESULTS: H2O2 induced Akt phosphorylation in a dose-dependent manner
      and also induced the phosphorylation of downstream effectors FKHR and GSK-3beta.
      LY markedly inhibited H2O2-mediated Akt phosphorylation and significantly
      enhanced caspase-associated and caspase-independent RPE cell death. CONCLUSIONS:
      A model oxidant, H2O2, induces PI3K and thereby activates Akt. Akt activation
      enhances RPE cell survival and thus may protect RPE cells from oxidant-induced
      cell death under normal circumstances and in disease states such as age-related
      macular degeneration (AMD).

PMID- 17003456
TI  - Effects of ethanol on photoreceptors and visual function in developing zebrafish.
AB  - PURPOSE: Children born to mothers who have consumed alcohol during pregnancy have
      an array of retinal abnormalities and visual dysfunctions. In the past, rodent
      systems have been used to study the teratogenic effects of ethanol on vertebrate
      embryonic development. The exact developmental windows in which ethanol causes
      specific developmental defects have been difficult to determine because rodents
      and other mammals develop in utero. In this study, we characterized how ethanol
      affects the function and development of the visual system in an ex utero
      embryonic system, the zebrafish. METHODS: Zebrafish embryos were raised in fish
      water containing various concentrations of ethanol from 2 to 5 days after
      fertilization. The effects of ethanol on retinal morphology were assessed by
      histologic and immunohistochemical analyses and those on retinal function were
      analyzed by optokinetic response (OKR) and electroretinography (ERG). RESULTS:
      Zebrafish embryos exposed to moderate and high levels of ethanol during early
      embryonic development had morphological abnormalities of the eye characterized by
      hypoplasia of the optic nerve and inhibition of photoreceptor outer segment
      growth. Ethanol treatment also caused an increased visual threshold as measured
      by the OKR. Analysis with the ERG indicated that there was a severe reduction of
      both the a- and b-waves, suggesting that ethanol affects the function of the
      photoreceptors. Indeed, low levels of ethanol that did not cause obvious
      morphologic changes in either the body or retina did affect both the OKR visual
      threshold and the a- and b-wave amplitudes. CONCLUSIONS: Ethanol affects
      photoreceptor function at low concentrations that do not disturb retinal
      morphology. Higher levels of ethanol inhibit photoreceptor development and cause
      hypoplasia of the optic nerve.

PMID- 17003458
TI  - Expression of costimulatory molecules on human retinoblastoma cells Y-79:
      functional expression of CD40 and B7H1.
AB  - PURPOSE: To examine the expression of various costimulatory molecules on the
      human retinoblastoma cell line Y-79 and assess the functional roles of selected
      costimulatory molecules. METHODS: Y-79 cells were incubated in the presence or
      absence of IFN-gamma, with or without irradiation (100 Gy). Expression of major
      histocompatibility complex (MHC) class I molecules, MHC class II, CD80, CD86,
      CD40, CD70, B7H1, B7DC, B7H2, OX40L, and 4-1BBL on Y-79 cells was measured by
      reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric
      analysis. The functional role of CD40-mediated interactions in modifying immune
      responses to Y-79 was assessed in vitro by using recombinant human CD40 ligand
      (rhCD40L). The costimulatory effect of B7H1-expressing IFN-gamma-treated Y-79
      cells on proliferation of purified T cells was studied in Y-79/T-cell coculture
      experiments with a blocking anti-B7H1 monoclonal antibody (mAb). RESULTS: CD40
      and B7H2 were consistently detected on Y-79 cells by RT-PCR and flow cytometry.
      Cell surface expression of CD40 was upregulated on stimulation by IFN-gamma
      alone, radiation alone, and IFN-gamma combined with radiation. B7H1 expression
      was induced by IFN-gamma stimulation and increased further when irradiated Y-79
      cells were stimulated by IFN-gamma. Treatment of Y-79 cells with rhCD40L enhanced
      cell surface expression of MHC class I and intercellular adhesion molecule (ICAM)
      1 and also stimulated monocyte chemotactic protein (MCP)-1 production.
      Proliferative response of purified CD3+ T cells costimulated with IFN-gamma
      stimulated Y-79 was significantly enhanced by the addition of anti-B7H1 mAb.
      CONCLUSIONS: These results suggest that CD40 expressed on Y-79 plays an important
      role in augmenting antitumor immunity. In contrast, the expression of B7H1 on IFN
      gamma-treated Y-79 cells contributes to the suppression of T cells. The dual
      effects of CD40 and B7H1 on Y-79 cells may contribute to positive or negative
      regulation of antitumor immune responses in human retinoblastoma.

PMID- 17003459
TI  - Sustained versus transient ERK1/2 signaling underlies the anti- and proapoptotic
      effects of oxidative stress in human RPE cells.
AB  - PURPOSE: Oxidative stress is thought to contribute to the pathogenesis of age
      related macular degeneration (AMD), which involves retinal pigmented epithelial
      (RPE) cell death. However, signaling pathways involved in the oxidative-stress
      induced RPE cell death are poorly understood. This study was conducted to
      investigate the involvement of the MAP kinase pathways during the induction of
      RPE cell death by oxidative stress. METHODS: ARPE-19 cells were exposed to the
      oxidant tert-butyl hydroperoxide (t-BHP). Cell viability was assessed by cell
      counting and MTT-staining, and apoptosis was quantified by TUNEL and flow
      cytometry. Activation of JNK1/3, p38 alphabeta MAPKs and ERK1/2 and their
      potential targets was detected by Western blot analysis and immunochemistry with
      specific anti-phospho protein antibodies. Specific pharmacologic inhibitors
      directed against the MAPKs were used to analyze the signaling involved in cell
      death of RPE cells exposed to t-BHP. RESULTS: Exposure of RPE cells to t-BHP,
      associated with increase in reactive oxygen species and intracellular glutathione
      depletion, induced time- and concentration-dependent apoptosis, which was
      associated with the accumulation of inactive ERK1/2 in cell nuclei and a
      transient and weak ERK1/2 activation. This activation was accompanied by a
      deactivation of P90(RSK), the major target of ERK1/2 and consequently by the
      delayed activation of its transcription factor CREB. MEK1/2 inhibition completely
      suppressed the transient activation of ERK1/2 and completely blocked apoptosis,
      demonstrating the role of the MEK-ERK module in mediating oxidative-stress
      induced RPE cell death. In contrast, neither JNKs nor p38 alphabeta MAPKs were
      involved in mediating t-BHP-induced apoptotic signaling in RPE cells.
      CONCLUSIONS: The results suggest that inhibiting the MEK-ERK module may allow the
      development of selective methods for treating oxidative-stress-induced RPE
      degeneration, such as AMD.

PMID- 17003460
TI  - Severity staging by early features of age-related maculopathy exhibits weak
      relationships with functional deficits on SWS grating acuity.
AB  - PURPOSE: To examine the relationship between short-wavelength-sensitive (SWS)
      resolution acuity and epidemiologically defined stages of early age-related
      maculopathy (ARM). METHODS: Subjects consisted of 88 adults aged 51 to 87 years.
      Psychophysical testing was undertaken in only one eye of each subject (the study
      eye). All study eyes had a LogMAR acuity of 0.30 (20/40 Snellen) or better. SWS
      and achromatic grating resolution acuity were measured at 6 degrees eccentricity
      from the fovea. Stereoscopic color fundus photographs centered on the macula were
      taken on both eyes of each subject and were graded using the Wisconsin Age
      Related Maculopathy Grading System (WARMGS). After grading, features of ARM were
      combined to assign a severity stage from 0 to 5 using the methods described by
      the Rotterdam Eye Study. Relationships between visual function, study eye ARM
      stage, and fellow eye status were examined with the use of standard statistical
      analysis. RESULTS: Although SWS resolution acuity was significantly reduced in
      eyes classified as having any ARM compared with eyes classified as having no ARM
      (P = 0.002), there was no relationship between the severity of functional
      deficits and the morphologic severity from stage 1 to stage 4. On reassigning
      subject eyes to a revised severity staging (stage 0, stages 1 to 4 combined, and
      stage 5), SWS acuity was significantly different among these three groups (P <
      0.001). No significant relationship was found between achromatic resolution
      acuity and ARM staging. The status of the fellow eye (advanced macular
      degeneration present or absent) was not significantly related to visual function
      in the study eye. CONCLUSIONS: Significant functional deficits in SWS resolution
      acuity were found in eyes with ARM features, but the severity of functional loss
      did not correlate well with the currently accepted method of assigning a
      morphologic severity stage. Longitudinal studies may reveal further information
      on the relationships between functional deficits, ARM status, disease
      progression, and outcome.

PMID- 17003461
TI  - Assessment of false positives with the Humphrey Field Analyzer II perimeter with
      the SITA Algorithm.
AB  - PURPOSE: To evaluate the effects of false-positive (FP) response errors on mean
      deviation (MD), pattern standard deviation (PSD), glaucoma hemifield test (GHT),
      and test duration in the Humphrey Field Analyzer's (HFA II) Swedish Interactive
      Threshold Algorithm (SITA; Carl Zeiss Meditec, Inc., Dublin, CA). METHODS: Five
      individuals with glaucoma (ages 52, 63, 69, 77, and 78 years) and five
      individuals with normal, healthy eyes (ages 25, 34, 43, 45, and 52 years),
      participated in the study. Each subject was experienced in automated perimetry
      and performed multiple, monocular baseline SITA-standard (SITA-S) 24-2 visual
      field tests. In addition, normal subjects completed SITA-S 24-2 field
      examinations in which known frequencies of FP error were introduced (0%, 5%, 10%,
      20%, or 33% frequency). Likewise, the subjects with glaucoma completed visual
      field examinations with 0%, 20%, and 33% error introduced during the test.
      RESULTS: Reported FP errors were significantly lower than the introduced
      frequency of error. The SITA algorithm more accurately identified FP errors when
      the MD and PSD diverged from normal. Test duration increased as introduced error
      frequencies increased. The Statpac single-field analyses indicated that two
      thirds of the tests with introduced errors produced a "low-patient-reliability"
      determination. CONCLUSIONS: HFA II SITA-S underestimates patients' FP errors,
      particularly among normal patients. High FP error frequencies can have adverse
      effects on MD and PSD, leading clinicians and researchers to an inaccurate
      determination of the amount and severity of visual field loss.

PMID- 17003462
TI  - Early vascular and neuronal changes in a VEGF transgenic mouse model of retinal
      neovascularization.
AB  - PURPOSE: To investigate early retinal changes in a vascular endothelial growth
      factor (VEGF) transgenic mouse (tr029VEGF; rhodopsin promoter) with long-term
      damage that mimics nonproliferative diabetic retinopathy (NPDR) and mild
      proliferative diabetic retinopathy (PDR). METHODS: Rhodopsin and VEGF expression
      was assessed up to postnatal day (P)28. Vascular and retinal changes were charted
      at P7 and P28 using sections and wholemounts stained with hematoxylin and eosin
      or isolectin IB4 Griffonia simplicifolia Samples were examined using light,
      fluorescence, and confocal microscopy. RESULTS: Rhodopsin was detected at P5 and
      reached mature levels by P15; VEGF protein expression was transient, peaking at
      P10 to P15. In wild-type (wt) mice at P7, vessels had formed in the nerve
      fiber/retinal ganglion cell layer and showed a centroperipheral maturational
      gradient; some capillaries had formed a second bed on the vitread side of the
      inner nuclear layer (INL). By P28, the retinal vasculature had three mature
      capillary beds, the third abutting the sclerad aspect of the INL. In tr029VEGF
      mice, capillary bed formation was accelerated compared with that in wt, with
      abnormal vessels extending to the sclerad side of the INL by P7 and abnormally
      penetrating the photoreceptors by P28. Compared with P7, vascular lesions were
      more numerous at P28 when capillary dropout was also evident. At both stages,
      retinal layers were thinned most where abnormal vessel growth was greatest.
      CONCLUSIONS: Concomitant damage to the vasculature and neural retina at early
      stages in tr029VEGF suggest that both tissues are affected, providing
      opportunities to examine early cellular events that lead to long-term disease.

PMID- 17003463
TI  - The effect of auditory and visual distracters on the useful field of view:
      implications for the driving task.
AB  - PURPOSE: The driving environment is becoming increasingly complex, including both
      visual and auditory distractions within the in-vehicle and external driving
      environments. This study was designed to investigate the effect of visual and
      auditory distractions on a performance measure that has been shown to be related
      to driving safety, the useful field of view. METHODS: A laboratory study recorded
      the useful field of view in 28 young visually normal adults (mean 22.6 +/- 2.2
      years). The useful field of view was measured in the presence and absence of
      visual distracters (of the same angular subtense as the target) and with three
      levels of auditory distraction (none, listening only, listening and responding).
      RESULTS: Central errors increased significantly (P < 0.05) in the presence of
      auditory but not visual distracters, while peripheral errors increased in the
      presence of both visual and auditory distracters. Peripheral errors increased
      with eccentricity and were greatest in the inferior region in the presence of
      distracters. CONCLUSIONS: Visual and auditory distracters reduce the extent of
      the useful field of view, and these effects are exacerbated in inferior and
      peripheral locations. This result has significant ramifications for road safety
      in an increasingly complex in-vehicle and driving environment.

PMID- 17003464
TI  - Predicting the optical performance of eyes implanted with IOLs to correct
      spherical aberration.
AB  - PURPOSE: To use powerful modeling techniques for predicting the optical
      performance of eyes implanted with different types of intraocular lenses (IOLs).
      This approach will allow performance of "virtual cataract surgery," with
      different IOL designs that can be used and physical parameters that may occur
      during actual surgery-in particular, in IOLs that correct spherical aberration.
      METHODS: A computer model was developed to predict the optical performance of
      individual eyes after IOL implantation. The approach was validated in a group of
      patients with eyes implanted with different IOLs. In these patients, corneal
      wavefront aberrations were calculated from elevations provided by
      videokeratography. Ocular aberrations were measured with a high-dynamic range
      Hartmann-Shack wavefront sensor. Misalignments (IOL tilt and decentration) were
      estimated with a new instrument, based on recording Purkinje images. This model
      of particular corneal aberrations and IOL parameters (intrinsic optical design
      details plus geometric location data) was used to estimate the total ocular
      aberrations after surgery and to compared them with actual aberrations measured
      directly with the wavefront sensor. RESULTS: The aberrations of implanted eyes
      predicted by the individualized optical models were well correlated with the
      actual aberration measured in each subject. This result indicates that the
      approach is adequate in evaluating the actual optical performance of different
      types of lenses. The model allows a large number of "virtual" surgeries to be
      performed, to test the performance of current or future IOL designs. CONCLUSIONS:
      A "virtual surgery" approach was designed to predict the optical performance in
      pseudophakic eyes. In each subject, it was possible to obtain the eye's optical
      performance with a particular IOL and biometric data after surgery. Specifically,
      this modeling can be used to evaluate the tolerances to misalignments and depth
      of focus of IOLs correcting spherical aberration in actual eyes. This approach is
      quite powerful and is especially applicable to the study of current and future
      aberration-correction IOL designs.

PMID- 17003465
TI  - Tumor suppression by p53 is mediated in part by the antiangiogenic activity of
      endostatin and tumstatin.
AB  - Recent research shows that p53 suppresses tumor angiogenesis by transcriptionally
      activating the alpha(II) collagen prolyl-4-hydroxylase gene. This results in the
      extracellular release of the potent endogenous angiogenesis inhibitors endostatin
      and tumstatin from collagens 18 and 4, respectively. The involvement of these
      inhibitors elucidates a molecular mechanism. By simultaneously repressing a
      multitude of proangiogenic pathways and by inducing antiangiogenic pathways, a
      tumor suppressor protein can prevent an incipient tumor from switching to the
      angiogenic phenotype. Thus, p53 guards the genome from cancer by controlling the
      three fundamental processes that are critical for growth of a primary tumor and
      its metastases-tumor cell proliferation, apoptosis, and tumor angiogenesis.

PMID- 17003466
TI  - Advances in understanding brassinosteroid signaling.
AB  - Brassinosteroids (BRs) function as signaling molecules in plants and are involved
      in processes such as stem elongation, vascular differentiation, male fertility,
      timing of senescence and flowering, leaf development, and resistance to biotic
      and abiotic stresses. Unlike animal steroids that are perceived by nuclear
      receptors, BRs are perceived by transmembrane receptor kinase complexes that
      initiate a phosphorylation-mediated signaling cascade to transduce the steroid
      signal. BR binding to the extracellular domain of the receptor BRI1 induces
      kinase activation and hetero-oligomerization with the second transmembrane kinase
      BAK1. Activated BRI1 then dissociates from the BRI1-interacting protein BKI1, a
      newly identified negative regulator of BR signaling. In the presence of BR, the
      kinase BIN2, which is the Arabidopsis homolog of GSK3 (glycogen synthase kinase
      3), is inhibited by an unknown mechanism, leading to dephosphorylation of BES1
      and BZR1 inside the nucleus. This allows BES1 and BZR1 to homodimerize or combine
      with other transcription factors to bind to promoters of BR-responsive genes.
      These studies of BR signaling in plants have revealed signaling pathways that are
      distinctly different from related ones operating in animal cells.

PMID- 17003467
TI  - mRNA regulation by Puf domain proteins.
AB  - Puf domain proteins bind specific sequences in mRNAs to regulate their
      translation or stability, or both. Neither the mechanism of their action nor the
      identities of targeted mRNAs have been well defined. Recent work suggests that
      Puf proteins generally act by recruiting Pop2, a deadenylation enzyme that is
      part of a large complex. Recent work from a separate group defines a subset of
      the Drosophila transcriptome that is bound by the fly Puf protein, Pumilio.
      Together, these papers substantially increase our understanding of the biology of
      the Puf family of mRNA regulators.

PMID- 17003469
TI  - MMPs in unusual places.

PMID- 17003470
TI  - What causes endothelial cell activation in preeclamptic women?

PMID- 17003471
TI  - Liver-type fatty acid-binding protein attenuates renal injury induced by
      unilateral ureteral obstruction.
AB  - Liver-type fatty-acid-binding protein (L-FABP), which has high affinity for long
      chain fatty acid oxidation products, may be an effective endogenous antioxidant.
      To examine the role of L-FABP in tubulointerstitial damage, we used a unilateral
      ureteral obstruction (UUO) model. We established human L-FABP (hL-FABP) gene
      transgenic (Tg) mice and compared the tubulointerstitial pathology of the Tg mice
      (n = 23) with that of the wild-type (WT) mice (n = 23). Mice were sacrificed on
      days 2, 4, 5, or 7 after UUO. Although mouse L-FABP was not expressed in WT mice,
      hL-FABP was expressed in the proximal tubules of the Tg mice with UUO (UUO-Tg)
      and in sham-operated Tg mice. The expression of renal hL-FABP was significantly
      increased in UUO-Tg compared with sham-operated Tg mice. The number of
      macrophages (F4/80) infiltrating the interstitium and the level of expression of
      MCP-1 and MCP-3 were significantly lower in UUO-Tg kidneys compared with UUO-WT
      kidneys. In UUO-Tg kidneys, the degree of the tubulointerstitial injury and the
      deposition of type I collagen were significantly lower than that of UUO-WT
      kidneys. On day 7, lipid peroxidation product accumulated in the UUO-WT kidneys
      but not in that of UUO-Tg kidneys. In conclusion, renal L-FABP may reduce the
      oxidative stress in the UUO model, ameliorating tubulointerstitial damage.

PMID- 17003472
TI  - Interferon-gamma plays protective roles in sodium arsenite-induced renal injury
      by up-regulating intrarenal multidrug resistance-associated protein 1 expression.
AB  - Subcutaneous injection of sodium arsenite (NaAs, 12.5 mg/kg) into BALB/c [wild
      type (WT)] mice causes acute renal dysfunction characterized by severe
      hemorrhages, acute tubular necrosis, and cast formation, with increases in serum
      blood urea nitrogen and creatinine levels. Concomitant enhancement in intrarenal
      interferon (IFN)-gamma expression prompted us to examine its roles in this
      pathology. IFN-gamma-deficient (IFN-gamma-/-) mice exhibited higher serum blood
      urea nitrogen and creatinine levels and exaggerated histopathological changes,
      compared with WT mice. Eventually, IFN-gamma-/- mice exhibited a high mortality
      (87.5%) within 24 hours after NaAs challenge, whereas most WT mice survived. The
      intrarenal arsenic concentration was significantly higher in IFN-gamma-/- mice
      later than 10 hours after NaAs treatment, with attenuated intrarenal expression
      of multidrug resistance-associated protein (MRP) 1, a main transporter for NaAs
      efflux, compared with WT mice. NF-E2-related factor (Nrf) 2 protein, a
      transcription factor crucial for MRP1 gene expression, was similarly increased in
      the kidneys of both strains of mice after NaAs treatment. In contrast, the
      absence of IFN-gamma augmented transforming growth factor-beta-Smad3 signal
      pathway and eventually enhanced the expression of activating transcription factor
      3, which is presumed to repress Nrf2-mediated MRP1 gene expression. Thus, IFN
      gamma can protect against NaAs-induced acute renal injury, probably by
      maintaining Nrf2-mediated intrarenal MRP1 gene expression.

PMID- 17003473
TI  - Overexpression of peroxisome proliferator-activated receptor gamma co-activator
      1alpha leads to muscle atrophy with depletion of ATP.
AB  - Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha)
      is a key nuclear receptor co-activator for mitochondrial biogenesis. Here we
      report that overexpression of PGC-1alpha in skeletal muscles increased
      mitochondrial number and caused atrophy of skeletal muscle, especially type 2B
      fiber-rich muscles (gastrocnemius, quadriceps, and plantaris). Muscle atrophy
      became evident at 25 weeks of age, and a portion of the muscle was replaced by
      adipocytes. Mice showed increased energy expenditure and reduced body weight;
      thyroid hormone levels were normal. Mitochondria exhibited normal respiratory
      chain activity per mitochondrion; however, mitochondrial respiration was not
      inhibited by an ATP synthase inhibitor, oligomycin, clearly indicating that
      oxidative phosphorylation was uncoupled. Accordingly, ATP content in
      gastrocnemius was markedly reduced. A similar phenotype is observed in Luft's
      disease, a mitochondrial disorder that involves increased uncoupling of
      respiration and muscle atrophy. Our results indicate that overexpression of PGC
      1alpha in skeletal muscle increases not only mitochondrial biogenesis but also
      uncoupling of respiration, resulting in muscle atrophy.

PMID- 17003475
TI  - alpha-1 antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell
      apoptosis.
AB  - alpha-1 Antitrypsin (A1AT) is an abundant circulating serpin with a postulated
      function in the lung of potently inhibiting neutrophil-derived proteases.
      Emphysema attributable to A1AT deficiency led to the concept that a protease/anti
      protease imbalance mediates cigarette smoke-induced emphysema. We hypothesized
      that A1AT has other pathobiological relevant functions in addition to elastase
      inhibition. We demonstrate a direct prosurvival effect of A1AT through inhibition
      of lung alveolar endothelial cell apoptosis. Primary pulmonary endothelial cells
      internalized human A1AT, which co-localized with and inhibited staurosporine
      induced caspase-3 activation. In cell-free studies, native A1AT, but not
      conformers lacking an intact reactive center loop, inhibited the interaction of
      recombinant active caspase-3 with its specific substrate. Furthermore,
      overexpression of human A1AT via replication-deficient adeno-associated virus
      markedly attenuated alveolar wall destruction and oxidative stress caused by
      caspase-3 instillation in a mouse model of apoptosis-dependent emphysema. Our
      findings suggest that direct inhibition of active caspase-3 by A1AT may represent
      a novel anti-apoptotic mechanism relevant to disease processes characterized by
      excessive structural cell apoptosis, oxidative stress, and inflammation, such as
      pulmonary emphysema.

PMID- 17003474
TI  - Up-regulation of cation-independent mannose 6-phosphate receptor and endosomal
      lysosomal markers in surviving neurons after 192-IgG-saporin administrations into
      the adult rat brain.
AB  - The cation-independent mannose 6-phosphate receptor (CI-MPR) is a single
      transmembrane domain glycoprotein that plays a major role in the trafficking of
      lysosomal enzymes from the trans-Golgi network to the endosomal-lysosomal (EL)
      system. Because dysfunction of EL system is associated with a variety of
      neurodegenerative disorders, it is possible that the CI-MPR may have a role in
      regulating neuronal viability after toxicity/injury. In the present study, we
      report that 192-IgG-saporin-induced loss of basal forebrain cholinergic neurons
      causes a transient up-regulation of CI-MPR protein levels in surviving neurons of
      the basal forebrain and frontal cortex but not in the brainstem region, which was
      relatively spared by the immunotoxin. This was accompanied by a parallel time
      dependent increase in other EL markers, ie, cathepsin D, Rab5, and LAMP2 in the
      basal forebrain region, whereas in the frontal cortex the levels of cathepsin D,
      and to some extent Rab5, were increased. Given the critical role of the EL system
      in the clearance of abnormal proteins in response to changing conditions, it is
      likely that the observed increase in the CI-MPR and components of the EL system
      in surviving neurons after 192-IgG-saporin treatment represents an adaptive
      mechanism to restore the metabolic/structural abnormalities induced by the loss
      of cholin-ergic neurons.

PMID- 17003476
TI  - Placenta growth factor in diabetic wound healing: altered expression and
      therapeutic potential.
AB  - Reduced microcirculation and diminished expression of growth factors contribute
      to wound healing impairment in diabetes. Placenta growth factor (PlGF), an
      angiogenic mediator promoting pathophysiological neovascularization, is expressed
      during cutaneous wound healing and improves wound closure by enhancing
      angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate
      that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic
      mice overexpressing PlGF in the skin displayed accelerated wound closure compared
      with diabetic wild-type littermates. Moreover, diabetic wound treatment with an
      adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly
      accelerated the healing process compared with wounds treated with a control
      vector. The analysis of treated wounds showed that PlGF gene transfer improved
      granulation tissue formation, maturation, and vascularization, as well as
      monocytes/macrophages local recruitment. Platelet-derived growth factor,
      fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels
      were increased in AdCMV.PlGF-treated wounds, possibly enhancing PlGF-mediated
      effects. Finally, PlGF treatment stimulated cultured dermal fibroblast migration,
      pointing to a direct role of PlGF in accelerating granulation tissue maturation.
      In conclusion, our data indicate that reduced PlGF expression contributes to
      impaired wound healing in diabetes and that PlGF gene transfer to diabetic wounds
      exerts therapeutic activity by promoting different aspects of the repair process.

PMID- 17003477
TI  - Activated human T lymphocytes express cyclooxygenase-2 and produce proadipogenic
      prostaglandins that drive human orbital fibroblast differentiation to adipocytes.
AB  - The differentiation of preadipocyte fibroblasts to adipocytes is a crucial
      process to many disease states including obesity, cardiovascular, and autoimmune
      diseases. In Graves' disease, the orbit of the eye can become severely inflamed
      and infiltrated with T lymphocytes as part of the autoimmune process. The orbital
      fibroblasts convert to fat-like cells causing the eye to protrude, which is
      disfiguring and can lead to blindness. Recently, the transcription factor
      peroxisome proliferator activated receptor (PPAR)-gamma and its natural (15d
      PGJ2) and synthetic (thiazolidinedione-type) PPAR-gamma agonists have been shown
      to be crucial to the in vitro differentiation of preadipocyte fibroblasts to
      adipocytes. We show herein several novel findings. First, that activated T
      lymphocytes from Graves' patients drive the differentiation of PPAR-gamma
      expressing orbital fibroblasts to adipocytes. Second, this adipogenic
      differentiation is blocked by nonselective small molecule cyclooxygenase (Cox)
      1/Cox-2 inhibitors and by Cox-2 selective inhibitors. Third, activated, but not
      naive, human T cells highly express Cox-2 and synthesize prostaglandin D2 and
      related prostaglandins that are PPAR-gamma ligands. These provocative new
      findings provide evidence for how activated T lymphocytes, through production of
      PPAR-gamma ligands, profoundly influence human fibroblast differentiation to
      adipocytes. They also suggest the possibility that, in addition to the orbit, T
      lymphocytes influence the deposition of fat in other tissues.

PMID- 17003478
TI  - Peroxiredoxin 6 is a potent cytoprotective enzyme in the epidermis.
AB  - Peroxiredoxin 6 is an enzyme that detoxifies hydrogen peroxide and various
      organic peroxides. In previous studies we found strongly increased expression of
      peroxiredoxin 6 in the hyperproliferative epidermis of wounded and psoriatic
      skin, suggesting a role of this enzyme in epidermal homeostasis. To address this
      question, we generated transgenic mice overexpressing peroxiredoxin 6 in the
      epidermis. Cultured keratinocytes from transgenic mice showed enhanced resistance
      to the toxicity of various agents that induce oxidative stress. However,
      overexpression of peroxiredoxin 6 did not affect skin morphogenesis or
      homeostasis. On skin injury, enhancement of wound closure was observed in aged
      animals. Most importantly, peroxiredoxin 6 overexpression strongly reduced the
      number of apoptotic cells after UVA or UVB irradiation. These findings
      demonstrate that peroxiredoxin 6 protects keratinocytes from cell death induced
      by reactive oxygen species in vitro and in vivo, suggesting that activation of
      this enzyme could be a novel strategy for skin protection under stress
      conditions.

PMID- 17003479
TI  - Expression of the Notch signaling pathway and effect on exocrine cell
      proliferation in adult rat pancreas.
AB  - When pancreatic tissue is injured after duct obstruction, acinoductal metaplasia
      is observed. Similar metaplastic changes occur when exocrine pancreatic cells are
      isolated and cultured. We demonstrate that under these experimental conditions
      the exocrine acinar cells lose their differentiated characteristics: expression
      of the acinar transcription factors p48/Ptf1alpha and Mist1 is decreased or lost,
      whereas expression of the embryonic transcription factor Pdx1 is increased. The
      receptors Notch1 and Notch2, members of the DSL family of Notch ligands, and the
      target genes in the Notch-signaling pathway Hes1, Hey1, and Hey2 become strongly
      up-regulated. We noted also reduced expression of Sel1L, a Notch repressor that
      is normally highly expressed in exocrine pancreas. Stimulation of Notch by its
      ligand Jagged1 diminished the proliferation of cultured metaplastic exocrine
      cells. Chemical inhibition of Notch signaling resulted in increased proliferation
      and induction of the cell-cycle regulator p21Cip1. This effect seems to be Hes1
      independent and mainly coincides with decreased Hey1 and Hey2 mRNA expression. In
      conclusion, we demonstrate that during acinoductal metaplasia the Notch-signaling
      pathway is activated concomitantly with changes in transcription factor
      expression of pancreatic acinar cells. In addition, we show that Notch signaling
      is implicated in the suppression of proliferation of these metaplastic exocrine
      cells. The latter may be important in protection from neoplastic transformation.

PMID- 17003480
TI  - Hepatitis B virus promotes angiopoietin-2 expression in liver tissue: role of HBV
      x protein.
AB  - The progression of chronic hepatitis B (CHB) is related to fibrosis and to the
      emergence of intrahepatic anomalous vascular structures. Hepatitis B virus (HBV)
      X protein transactivator (HBx) may play a significant role in both processes. To
      analyze how HBV induces vascular growth and remodeling in vivo, we assessed the
      expression of angiopoietin-2 (Ang2) in liver biopsies from CHB patients by
      reverse transcriptase-polymerase chain reaction, Western blotting, and
      immunohistochemistry because of the relevant role of Ang2 in vascular
      development, remodeling, and tumor promotion. In addition, we analyzed the
      influence of HBx in the expression of Ang2 in HBx-expressing hepatocyte cell
      lines and in hepatic stellate cells stimulated with conditional medium from HBx
      hepatocytes. Ang2 expression was clearly up-regulated at both mRNA and protein
      levels in the liver of CHB patients, showing an intense staining of inflammatory
      infiltrates and vascular structures at inflamed portal areas. HBx-expressing
      hepatocytes and stimulated stellate cells showed a significant induction of Ang2
      expression. PI3K inhibitor and antioxidants repressed the 64-kd Ang2 form but
      further enhanced the inflammation-related 50-kd molecular species. Therefore, HBx
      could account for the induction of Ang2 observed in CHB, especially the 50-kd
      form, contributing to pathological angiogenesis and hepatocellular carcinoma
      progression.

PMID- 17003482
TI  - Inhibition of intrahepatic bile duct dilation of the polycystic kidney rat with a
      novel tyrosine kinase inhibitor gefitinib.
AB  - The polycystic kidney (PCK) rat represents a liver and kidney cyst pathology
      corresponding to Caroli's disease with congenital hepatic fibrosis and autosomal
      recessive polycystic kidney disease. We previously reported that an epidermal
      growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa),
      significantly inhibited the abnormal growth of biliary epithelial cells of PCK
      rats in vitro. This study investigated the effects of gefitinib on cyst
      pathogenesis of the PCK rat both in vitro and in vivo. A three-dimensional
      culture model of biliary epithelial cells in the collagen gel matrix was used for
      in vitro analysis. For in vivo experiments, PCK and control rats were treated
      with gefitinib between 3 and 10 weeks of age. In vitro, gefitinib had strong
      inhibitory effects on biliary cyst formation of PCK rats. In vivo, treatment with
      gefitinib significantly inhibited the cystic dilatation of the intrahepatic bile
      ducts of PCK rats, which was accompanied by improvement of liver fibrosis. By
      contrast, no beneficial effects were observed on renal cyst development because
      of the treatment. These results suggest that signaling pathways mediated by
      epidermal growth factor receptor are involved in biliary dysgenesis of the PCK
      rat, with the mechanisms of cyst progression being different between the liver
      and kidney.

PMID- 17003481
TI  - Posttranslationally modified proteins as mediators of sustained intestinal
      inflammation.
AB  - Oxidative and carbonyl stress leads to generation of N(epsilon)
      carboxymethyllysine-modified proteins (CML-mps), which are known to bind the
      receptor for advanced glycation end products (RAGE) and induce nuclear factor
      (NF)-kappaB-dependent proinflammatory gene expression. To determine the impact of
      CML-mps in vivo, RAGE-dependent sustained NF-kappaB activation was studied in
      resection gut specimens from patients with inflammatory bowel disease. Inflamed
      gut biopsy tissue demonstrated a significant up-regulation of RAGE and increased
      NF-kappaB activation. Protein extracts from the inflamed zones, but not from
      noninflamed resection borders, caused perpetuated NF-kappaB activation in
      cultured endothelial cells, which was mediated by CML-mps including CML-modified
      S100 proteins. The resulting NF-kappaB activation, lasting 5 days, was primarily
      inhibited by either depletion of CML-mps or by the addition of sRAGE, p44/42 and
      p38 MAPKinase-specific inhibitors. Consistently, CML-mps isolated from inflamed
      gut areas and rectally applied into mice caused NF-kappaB activation, increased
      proinflammatory gene expression, and histologically detectable inflammation in
      wild-type mice, but not in RAGE-/- mice. A comparable up-regulation of NF-kappaB
      and inflammation on rectal application of CML-mps was observed in IL-10-/- mice.
      Thus, CML-mps generated in inflammatory lesions have the capacity to elicit a
      RAGE-dependent intestinal inflammatory response.

PMID- 17003483
TI  - Peroxisomal localization of hypoxia-inducible factors and hypoxia-inducible
      factor regulatory hydroxylases in primary rat hepatocytes exposed to hypoxia
      reoxygenation.
AB  - Many signals involved in pathophysiology are controlled by hypoxia-inducible
      factors (HIFs), transcription factors that induce expression of hypoxia
      responsive genes. HIFs are post-translationally regulated by a family of O2
      dependent HIF hydroxylases: four prolyl 4-hydroxylases and an asparaginyl
      hydroxylase. Most of these enzymes are abundant in resting liver, which is itself
      unique because of its physiological O2 gradient, and they can exist in both
      nuclear and cytoplasmic pools. In this study, we analyzed the cellular
      localization of endogenous HIFs and their regulatory hydroxylases in primary rat
      hepatocytes cultured under hypoxia-reoxygenation conditions. In hepatocytes,
      hypoxia targeted HIF-1alpha to the peroxisome, rather than the nucleus, where it
      co-localized with von Hippel-Lindau tumor suppressor protein and the HIF
      hydroxylases. Confocal immunofluorescence microscopy demonstrated that the HIF
      hydroxylases translocated from the nucleus to the cytoplasm in response to
      hypoxia, with increased accumulation in peroxisomes on reoxygenation. These
      results were confirmed via immunotransmission electron microscopy and Western
      blotting. Surprisingly, in resting liver tissue, perivenous localization of the
      HIF hydroxylases was observed, consistent with areas of low pO2. In conclusion,
      these studies establish the peroxisome as a highly relevant site of subcellular
      localization and function for the endogenous HIF pathway in hepatocytes.

PMID- 17003484
TI  - Intercellular adhesion molecule-1 is required for the early formation of
      granulomas and participates in the resistance of mice to the infection with the
      fungus Paracoccidioides brasiliensis.
AB  - The migration of leukocytes to inflammatory sites elicited by Paracoccidioides
      brasiliensis is supposed to be coordinated by cytokines and chemokines. Here, we
      investigated the role of intercellular adhesion molecule-1 (ICAM-1) in recruiting
      inflammatory cells to lungs of mice infected with P. brasiliensis and in
      determining the outcome of the disease. Expression of ICAM-1 was up-regulated on
      T lymphocytes after infection with the fungus, and its expression was dependent
      on interferon-gamma, tumor necrosis factor-alpha, and interleukin-12. Moreover,
      the absence of ICAM-1 resulted in high susceptibility to the infection and
      delayed formation of granulomatous lesions. In addition, the absence of ICAM-1
      resulted in increased growth and dissemination of fungus, decreased number of
      CD3+CD4+ and CD3+CD8+ T cells, and increased production of interleukin-4 in the
      inflammatory site. The organization of a granulomatous reaction in mice deficient
      of ICAM-1 was delayed, starting only on day 60 after infection, whereas in wild
      type mice it was complete on day 30 of infection. These data show that ICAM-1 is
      effectively involved in cellular migration and in the organization of the
      granulomatous lesion caused by the fungus P. brasiliensis.

PMID- 17003485
TI  - ERK, p38, and Smad signaling pathways differentially regulate transforming growth
      factor-beta1 autoinduction in proximal tubular epithelial cells.
AB  - Transforming growth factor (TGF)-beta1 is a mediator of the final common pathway
      of fibrosis associated with progressive renal disease, a process in which
      proximal tubular cells (PTCs) are known to play an important part. The aim of the
      current study was to examine the mechanism of PTC TGF-beta1 autoinduction. The
      addition of TGF-beta1 led to increased amounts of TGF-beta1 mRNA and increased de
      novo protein synthesis. The addition of TGF-beta1 led to increased
      phosphorylation of R-Smads and activation of extracellular signal-regulated
      kinase mitogen-activated protein (MAP) kinase and p38 MAP kinase pathways. Use of
      a dominant-negative Smad3 (Smad3 DN) expression vector, Smad3 small interfering
      RNA, and inhibition of extracellular signal-regulated kinase and p38 MAP kinase
      pathways with the chemical inhibitors PD98059 or SB203580 suggested that
      activation of these signaling pathways occurred independently. Smad3 DN
      expression, Smad3 small interfering RNA, or the addition of PD98059 inhibited TGF
      beta1-dependent stimulation of TGF-beta1 mRNA. Furthermore, Smad3 blockade
      specifically inhibited activation of the transcription factor AP-1 by TGF-beta1,
      whereas PD98059 prevented TGF-beta1-dependent nuclear factor-kappaB activation.
      In contrast inhibition of p38 MAP kinase inhibited de novo TGF-beta1 protein
      synthesis but did not influence TGF-beta1 mRNA expression or activation of either
      transcription factor. In summary, in PTCs, TGF-beta1 autoinduction requires the
      coordinated action of independently regulated Smad and non-Smad pathways.
      Furthermore these pathways regulate distinct transcriptional and translational
      components of TGF-beta1 synthesis.

PMID- 17003486
TI  - Tumor necrosis factor-alpha and interleukin-1beta regulate interleukin-8
      expression in third trimester decidual cells: implications for the genesis of
      chorioamnionitis.
AB  - Chorioamnionitis is associated with intense neutrophil infiltration of the
      decidua. We therefore determined whether chorioamnionitis enhances decidual
      interleukin-8 (IL-8) expression and examined cytokine-regulated decidual IL-8
      expression. Decidua from chorioamnionitis-complicated pregnancies, but not term
      controls, displayed marked IL-8 immunohistochemical staining and a dense
      neutrophil infiltrate. Reverse transcriptase-polymerase chain reaction of
      microdissected decidual cells identified IL-8 mRNA, confirming decidual synthesis
      of IL-8. Confluent leukocyte-free term decidual cells were primed with 10(-8)
      mol/L estradiol (E2) or E2 + 10(-7) mol/L medroxyprogesterone acetate to mimic
      the steroidal milieu of pregnancy. Compared with cultures maintained in E2 alone,
      E2 + medroxyprogesterone acetate neither significantly affected IL-8 levels nor
      altered the response to the cytokines. The addition of 1.0 ng/ml tumor necrosis
      factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1beta) increased IL-8
      secretion levels by 236.6 +/- 51.4- and 1062.6 +/- 254.3-fold, respectively (n =
      8, mean +/- SEM, P < 0.05), as measured by enzyme-linked immunosorbent assay.
      Concentration-response studies revealed that 0.01 ng/ml TNF-alpha and IL-1beta
      elevated IL-8 output by 10- and 100-fold, respectively. Western blotting
      confirmed these results, and quantitative reverse transcriptase-polymerase chain
      reaction demonstrated parallel changes in mRNA levels. In conclusion, IL-8 is
      strongly expressed in term decidua during chorioamnionitis, and TNF-alpha and IL
      1beta enhance IL-8 expression in term decidual cells, suggesting that these
      cytokines are important regulators of chorioamnionitis-related decidual
      neutrophil infiltration.

PMID- 17003487
TI  - Down-regulation of ubiquitin ligase Cbl induced by twist haploinsufficiency in
      Saethre-Chotzen syndrome results in increased PI3K/Akt signaling and osteoblast
      proliferation.
AB  - Genetic mutations of Twist, a basic helix-loop-helix transcription factor, induce
      premature fusion of cranial sutures in Saethre-Chotzen syndrome (SCS). We report
      here a previously undescribed mechanism involved in the altered
      osteoblastogenesis in SCS. Cranial osteoblasts from an SCS patient with a Twist
      mutation causing basic helix-loop-helix deletion exhibited decreased expression
      of E3 ubiquitin ligase Cbl compared with wild-type osteoblasts. This was
      associated with decreased ubiquitin-mediated degradation of phosphatidyl inositol
      3 kinase (PI3K) and increased PI3K expression and PI3K/Akt signaling. Increased
      PI3K immunoreactivity was also found in osteoblasts in histological sections of
      affected cranial sutures from SCS patients. Transfection with Twist or Cbl
      abolished the increased PI3K/Akt signaling in Twist mutant osteoblasts. Forced
      overexpression of Cbl did not correct the altered expression of osteoblast
      differentiation markers in Twist mutant cells. In contrast, pharmacological
      inhibition of PI3K/Akt, but not ERK signaling, corrected the increased cell
      growth in Twist mutant osteoblasts. The results show that Twist
      haploinsufficiency results in decreased Cbl-mediated PI3K degradation in
      osteoblasts, causing PI3K accumulation and activation of PI3K/Akt-dependent
      osteoblast growth. This provides genetic and biochemical evidence for a role for
      Cbl-mediated PI3K signaling in the altered osteoblast phenotype induced by Twist
      haploinsufficiency in SCS.

PMID- 17003488
TI  - Impact of the loss of Hoxa5 function on lung alveogenesis.
AB  - The involvement of genes controlling embryonic processes in the etiology of
      diseases often escapes attention because of the focus given to their inherent
      developmental role. Hoxa5 belongs to the Hox gene family encoding transcription
      factors known for their role in skeletal patterning. Hoxa5 is required for
      embryonic respiratory tract morphogenesis. We now show that the loss of Hoxa5
      function has severe repercussions on postnatal lung development. Hoxa5-/- lungs
      present an emphysema-like morphology because of impaired alveogenesis. Chronic
      inflammation characteristics, including goblet cell hyperplasia, mucus
      hypersecretion, and recruitment of inflammatory cells, were also observed.
      Altered cell specification during lung morphogenesis triggered goblet cell
      anomalies. In addition, the defective motility of alveolar myofibroblast
      precursors in the embryonic lung led to the mispositioning of the alveolar
      myofibroblasts and to abnormal elastin deposition postnatally. Both goblet cell
      hyperplasia and elastic fiber abnormalities contributed to the chronic
      physiopathological features of Hoxa5-/- lungs. They constituted an attractive
      stimulus to recruit activated macrophages that in turn generated a positive
      feedback loop that perpetuated macrophage accumulation in the lung. The present
      work corroborates the notion that altered Hox gene expression may predispose to
      lung pathologies.

PMID- 17003489
TI  - Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified
      adenine during oxidative stress-induced renal carcinogenesis.
AB  - Oxidative stress is a persistent threat to the genome and is associated with
      major causes of human mortality, including cancer, atherosclerosis, and aging.
      Here we established a method to generate libraries of genomic DNA fragments
      containing oxidatively modified bases by using specific monoclonal antibodies to
      immunoprecipitate enzyme-digested genome DNA. We applied this technique to two
      different base modifications, 8-hydroxyguanine and 1,N6-propanoadenine (acrotein
      Ade), in a ferric nitrilotriacetate-induced murine renal carcinogenesis model.
      Renal cortical genomic DNA derived from 10- to 12-week-old male C57BL/6 mice, of
      untreated control or 6 hours after intraperitoneal injection of 3 mg iron/kg
      ferric nitrilotriacetate, was enzyme digested, immunoprecipitated, cloned, and
      mapped to each chromosome. The results revealed that distribution of the two
      modified bases was not random but differed in terms of chromosomes, gene size,
      and expression, which could be partially explained by chromosomal territory. In
      the wild-type mice, low GC content areas were more likely to harbor the two
      modified bases. Knockout of OGG1, a repair enzyme for genomic 8-hydroxyguanine,
      increased the amounts of acrolein-Ade as determined by quantitative polymerase
      chain reaction analyses. This versatile technique would introduce a novel
      research area as a high-throughput screening method for critical genomic loci
      under oxidative stress.

PMID- 17003490
TI  - Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin
      positive inclusions delineated by ubiquitin immunohistochemistry and novel
      monoclonal antibodies.
AB  - Frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) is
      a common neuropathological subtype of frontotemporal dementia. Although this
      subtype of frontotemporal dementia is defined by the presence of ubiquitin
      positive but tau- and alpha-synuclein-negative inclusions, it is unclear whether
      all cases of FTLD-U have the same underlying pathogenesis. Examination of tissue
      sections from FTLD-U brains stained with anti-ubiquitin antibodies revealed
      heterogeneity in the morphological characteristics of pathological inclusions
      among subsets of cases. Three types of FTLD-U were delineated based on morphology
      and distribution of ubiquitin-positive inclusions. To address the hypothesis that
      FTLD-U is pathologically heterogeneous, novel monoclonal antibodies (mAbs) were
      generated by immunization of mice with high molecular mass (Mr > 250 kd)
      insoluble material prepared by biochemical fractionation of FTLD-U brains. Novel
      mAbs were identified that immunolabeled all of the ubiquitin-positive inclusions
      in one subset of FTLD-U cases, whereas other mAbs stained the ubiquitin-positive
      inclusions in a second subset of cases. These novel mAbs did not stain inclusions
      in other neurodegenerative disorders, including tauopathies and alpha
      synucleinopathies. Therefore, ubiquitin immunohistochemistry and the
      immunostaining properties of the novel mAbs generated here suggest that FTLD-U is
      pathologically heterogeneous. Identification of the disease proteins recognized
      by these mAbs will further advance understanding of molecular substrates of FTLD
      U neurodegenerative pathways.

PMID- 17003491
TI  - Effects of glatiramer acetate and interferon-beta on neurodegeneration in a model
      of multiple sclerosis: a comparative study.
AB  - Axonal destruction and neuronal loss occur early during multiple sclerosis (MS),
      an autoimmune inflammatory central nervous system disease that frequently
      manifests with acute optic neuritis. Glatiramer acetate (GA) and interferon-beta
      1b (IFN-beta-1b) are two immunomodulatory agents that have been shown to decrease
      the frequency of MS relapses. However, the question of whether these substances
      can slow neurodegeneration in MS patients is the subject of controversy. In a rat
      model of experimental autoimmune encephalomyelitis, we investigated the effects
      of GA and IFN-beta-1b on the survival of retinal ganglion cells (RGCs), the
      neurons that form the axons of the optic nerve. For each substance, therapy was
      started 14 days before immunization, on the day of immunization, or on the day of
      clinical disease onset. After myelin oligodendrocyte glycoprotein-induced
      experimental autoimmune encephalomyelitis became clinically manifest, optic
      neuritis was monitored by recording visual evoked potentials. The function of
      RGCs was measured by electroretinograms. Although early GA or IFN-beta-1b
      treatment showed benefit on disease activity, only treatment with GA exerted
      protective effects on RGCs, as revealed by measuring neurodegeneration and
      neuronal function. Furthermore, we demonstrate that this GA-induced
      neuroprotection does not exclusively depend on the reduction of inflammatory
      infiltrates within the optic nerve.

PMID- 17003492
TI  - Cortical neuronal and glial pathology in TgTauP301L transgenic mice: neuronal
      degeneration, memory disturbance, and phenotypic variation.
AB  - Recapitulation of tau pathologies in an animal model has been a long-standing
      goal in neurodegenerative disease research. We generated transgenic (TgTauP301L)
      mice expressing a frontotemporal dementia with parkinsonism linked to chromosome
      17 (FTPD-17) mutation within the longest form of tau (2N, 4R). TgTauP301L mice
      developed florid pathology including neuronal pretangles, numerous Gallyas-Braak
      positive neurofibrillary tangles, and glial fibrillary tangles in the
      frontotemporal areas of the cerebrum, in the brainstem, and to a lesser extent in
      the spinal cord. These features were accompanied by gliosis, neuronal loss, and
      cerebral atrophy. Accumulated tau was hyperphosphorylated, conformationally
      changed, ubiquitinated, and sarkosyl-insoluble, with electron microscopy
      demonstrating wavy filaments. Aged TgTauP301L mice exhibited impairment in
      hippocampally dependent and independent behavioral paradigms, with impairments
      closely related to the presence of tau pathologies and levels of insoluble tau
      protein. We conclude that TgTauP301L mice recreate the substantial phenotypic
      variation and spectrum of pathologies seen in FTDP-17 patients. Identification of
      genetic and/or environmental factors modifying the tau phenotype in these mice
      may shed light on factors modulating human tauopathies. These transgenic mice may
      aid therapeutic development for FTDP-17 and other diseases featuring
      accumulations of four-repeat tau, such as Alzheimer's disease, corticobasal
      degeneration, and progressive supranuclear palsy.

PMID- 17003493
TI  - Tumor cell plasticity in uveal melanoma: microenvironment directed dampening of
      the invasive and metastatic genotype and phenotype accompanies the generation of
      vasculogenic mimicry patterns.
AB  - The histological detection of laminin-rich vasculogenic mimicry patterns in human
      primary uveal melanomas is associated with death from metastases. We therefore
      hypothesized that highly invasive uveal melanoma cells forming vasculogenic
      mimicry patterns after exposure to a laminin-rich three-dimensional
      microenvironment would differentially express genes associated with invasive and
      metastatic behavior. However, we discovered that genes associated with
      differentiation (GDF15 and ATF3) and suppression of proliferation (CDKNa1/p21)
      were up-regulated in highly invasive uveal melanoma cells forming vasculogenic
      mimicry patterns, and genes associated with promotion of invasive and metastatic
      behavior such as CD44, CCNE2 (cyclin E2), THBS1 (thrombospondin 1), and CSPG2
      (chondroitin sulfate proteoglycan; versican) were down-regulated. After forming
      vasculogenic mimicry patterns, uveal melanoma cells invaded only short distances,
      failed to replicate, and changed morphologically from the invasive epithelioid to
      the indolent spindle A phenotype. In human tissue samples, uveal melanoma cells
      within vasculogenic mimicry patterns assumed the spindle A morphology, and the
      expression of Ki67 was significantly reduced in adjacent melanoma cells. Thus,
      the generation of vasculogenic mimicry patterns is accompanied by dampening of
      the invasive and metastatic uveal melanoma genotype and phenotype and underscores
      the plasticity of these cells in response to cues from the microenvironment.

PMID- 17003494
TI  - Matrix metalloproteinase 3 is present in the cell nucleus and is involved in
      apoptosis.
AB  - Matrix metalloproteinase (MMP)-3 is a protease involved in cancer progression and
      tissue remodeling. Using immunofluorescence and immunoelectron microscopy, we
      identified nuclear localization of MMP-3 in several cultured cell types and in
      human liver tissue sections. Western blot analysis of nuclear extracts revealed
      two immunoreactive forms of MMP-3 at 35 and 45 kd, with the 35-kd form exhibiting
      caseinolytic activity. By transient transfection, we expressed active MMP-3 fused
      to the enhanced green fluorescent protein (EGFP/aMMP-3) in Chinese hamster ovary
      cells. We showed that EGFP/aMMP-3 translocates into the nucleus. A functional
      nuclear localization signal was demonstrated by the loss of nuclear translocation
      after site-directed mutagenesis of a putative nuclear localization signal and by
      the ability of the MMP-3 nuclear localization signal to drive a heterologous
      protein into the nucleus. Finally, expression by Chinese hamster ovary cells of
      EGFP/aMMP-3 induced a twofold increase of apoptosis rate, compared with EGFP/pro
      MMP-3, which does not translocate to the nucleus. Increased apoptosis was
      abolished by site-directed mutagenesis of the catalytic site of MMP-3 or by using
      the MMP inhibitor GM6001. This study elucidates for the first time the mechanisms
      of nuclear localization of a MMP and shows that nuclear MMP-3 can induce
      apoptosis via its catalytic activity.

PMID- 17003495
TI  - Erbb2 regulates inflammation and proliferation in the skin after ultraviolet
      irradiation.
AB  - Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin
      cancer, the most common form of cancer in the United States. UV irradiation has a
      variety of effects on the skin associated with carcinogenesis, including DNA
      damage and effects on signal transduction. The alterations in signaling caused by
      UV regulate inflammation, cell proliferation, and apoptosis. UV also activates
      the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this
      study, we demonstrate that the UV-induced activation of Erbb2 regulates the
      response of the skin to UV. Inhibition or knockdown of Erbb2 before UV
      irradiation suppressed cell proliferation, cell survival, and inflammation after
      UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous
      proinflammatory genes that are regulated by the transcription factors nuclear
      factor-kappaB and Comp1, including interleukin-1beta, prostaglandin
      endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These
      results reveal the influence of Erbb2 on the UV response and suggest a role for
      Erbb2 in UV-induced pathologies such as skin cancer.

PMID- 17003496
TI  - Hyaluronidase expression induces prostate tumor metastasis in an orthotopic mouse
      model.
AB  - Molecular mechanisms of prostate cancer progression are frequently studied in
      mice by orthotopic injection of aggressive cell lines, which yield primary tumors
      that spontaneously metastasize to lymph nodes. In this report, we characterized
      the human prostate carcinoma cell line 22Rv1 in an orthotopic system and
      evaluated the functional relevance of the hyaluronidase Hyal1, a correlate of
      invasive human prostate cancer, to progression in this model. To provide real
      time insights into these processes, we first validated use of an epidermal growth
      factor-conjugated fluorophore to illuminate orthotopic prostate tumors and their
      metastases in whole animal imaging. Animals receiving intraprostatic injections
      were tracked throughout a 6-week period. Tumor sizes were correlated 92% with
      total fluorescence intensities of 22 prostate tumors. In contrast to the highly
      tumorigenic and metastatic PC3M-LN4 cells, the 22Rv1 line was orthotopically
      tumorigenic but not metastatic, despite larger tumor sizes. Lymph node metastasis
      was successfully imaged in animals with PC3M-LN4 tumors on endpoint dissection.
      Stable transfection of 22Rv1 cells with Hyal1 did not alter growth kinetics of
      primary orthotopic tumors, but all animals implanted with Hyal1 transfectants
      exhibited tumor-positive para-aortic lymph nodes. Hyal1 is implicated as an
      inducer of prostate cancer metastatic progression.

PMID- 17003497
TI  - H-REV107-1 stimulates growth in non-small cell lung carcinomas via the activation
      of mitogenic signaling.
AB  - H-REV107-1, a known member of the class II tumor suppressor gene family, is
      involved in the regulation of differentiation and survival. We analyzed H-REV107
      1 in non-small cell lung carcinomas, in normal lung, and in immortalized and
      tumor-derived cell lines. Sixty-eight percent of lung tumors revealed positive H
      REV107-1-specific staining. Furthermore, survival analysis demonstrated a
      significant association of cytoplasmic H-REV107-1 with decreased patient
      survival. This suggested that H-REV107-1, known as a tumor suppressor, plays a
      different role in non-small cell lung carcinomas. Knock-down of H-REV107-1
      expression in lung carcinoma cells inhibited anchorage-dependent and anchorage
      independent growth whereas overexpression of H-REV107-1 induced tumor cell
      proliferation. Consistent with results of the survival analysis, cytoplasmic
      localization of the protein was essential for this growth-inducing function.
      Analysis of signaling pathways potentially involved in this process demonstrated
      that overexpression of H-REV107-1 stimulated RAS-GTPase activity, ERK1,2
      phosphorylation, and caveolin-1 expression in the cell lines analyzed. These
      results indicate that H-REV107-1 is deficient in its function as a tumor
      suppressor in non-small cell lung carcinomas and is required for proliferation
      and anchorage-independent growth in cells expressing high levels of the protein,
      thus contributing to tumor progression in a subset of non-small cell lung
      carcinomas.

PMID- 17003498
TI  - Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral
      blood CD34-positive cells for functional bone healing.
AB  - Failures in fracture healing are mainly caused by a lack of vascularization.
      Adult human circulating CD34+ cells, an endothelial/hematopoietic progenitor
      enriched cell population, have been reported to differentiate into osteoblasts in
      vitro; however, the therapeutic potential of CD34+ cells for fracture healing is
      still unclear. Therefore, we performed a series of experiments to test our
      hypothesis that functional fracture healing is supported by vasculogenesis and
      osteogenesis via regenerative plasticity of CD34+ cells. Peripheral blood CD34+
      cells, isolated from total mononuclear cells of adult human volunteers, showed
      gene expression of osteocalcin in 4 of 20 freshly isolated cells by single cell
      reverse transcriptase-polymerase chain reaction analysis. Phosphate-buffered
      saline, mononuclear cells, or CD34+ cells were intravenously transplanted after
      producing nonhealing femoral fractures in nude rats. Reverse transcriptase
      polymerase chain reaction and immunohistochemical staining at the peri-fracture
      site demonstrated molecular and histological expression of human-specific markers
      for endothelial cells and osteoblasts at week 2. Functional bone healing assessed
      by biomechanical as well as radiological and histological examinations was
      significantly enhanced by CD34+ cell transplantation compared with the other
      groups. Our data suggest circulating human CD34+ cells have therapeutic potential
      to promote an environment conducive to neovascularization and osteogenesis in
      damaged skeletal tissue, allowing the complete healing of fractures.

PMID- 17003499
TI  - Recruitment of a prostaglandin E receptor subtype, EP3-expressing bone marrow
      cells is crucial in wound-induced angiogenesis.
AB  - E-type prostaglandins have been reported to be proangiogenic in vivo. Thus, we
      examined prostaglandin receptor signaling relevant to wound-induced angiogenesis.
      Full-thickness skin wounds were created on the backs of mice, and angiogenesis in
      wound granulation tissues was estimated. Wound closure and re-epithelization in
      EP3 receptor knockout mice (EP3-/-) were significantly delayed compared with
      their wild-type (WT) mice, whereas those in EP1-/-, EP2-/-, and EP4-/- were not
      delayed. Wound-induced angiogenesis estimated with CD31 immunohistochemistry in
      EP3-/- mice was significantly inhibited compared with that in WT mice.
      Immunoreactive vascular endothelial growth factor (VEGF) in wound granulation
      tissues in EP3-/- mice was markedly less than that in WT mice. Wound closure in
      WT mice was delayed significantly by VEGF neutralizing antibody compared with
      control IgG. Wound-induced angiogenesis and wound closure were significantly
      suppressed in EP3-/- bone marrow transplantation mice compared with those in WT
      bone marrow transplantation mice. These were accompanied with the reductions in
      accumulation of VEGF-expressing cells in wound granulation tissues and in
      mobilization of VEGF receptor 1-expressing leukocytes in peripheral circulation.
      These results indicate that the recruitment of EP3-expressing cells to wound
      granulation tissues is critical for surgical wound healing and angiogenesis via
      up-regulation of VEGF.

PMID- 17003500
TI  - Shed membrane particles from preeclamptic women generate vascular wall
      inflammation and blunt vascular contractility.
AB  - We investigated the role of microparticles in vascular dysfunction of the
      multisystemic disorder of preeclampsia in women's omental arteries or mouse
      arteries. Preeclamptic women displayed increased circulating levels of leukocyte-
      and platelet-derived microparticles compared with healthy pregnant individuals.
      Microparticles from preeclamptic, but not healthy, pregnant women induced ex vivo
      vascular hyporeactivity to serotonin in human omental arteries and mouse aortas.
      Hyporeactivity was reversed by a nitric-oxide (NO) synthase inhibitor and
      associated with increased NO production. In the presence of a cyclooxygenase
      (COX)-2 inhibitor, serotonin-mediated contraction was partially reduced in
      arteries treated with healthy microparticles but was abolished after treatment
      with preeclamptic microparticles. This was associated with increased 8
      isoprostane production. Preeclamptic microparticles induced up-regulation of
      inducible nitric-oxide synthase and COX-2 expression, evoked nuclear factor
      kappaB activation, and enhanced oxidative and nitrosative stress. Interestingly,
      the microparticles originating most probably from leukocytes were responsible for
      the COX-2 vasoconstrictor component of preeclamptic microparticles, whereas those
      of platelet origin were mainly involved in NO release. Moreover, vascular
      hyporeactivity was observed in arteries taken from mice treated in vivo with
      preeclamptic microparticles. This study demonstrates pathophysiological relevance
      and provides a paradoxical effect of preeclamptic microparticles associated with
      proinflammatory properties on vessels, leading to enhanced NO and superoxide
      anion levels and counteraction of increased COX-2 metabolites.

PMID- 17003503
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 17003501
TI  - Influence of endothelial cells on vascular smooth muscle cells phenotype after
      irradiation: implication in radiation-induced vascular damages.
AB  - Damage to vessels is one of the most common effects of therapeutic irradiation on
      normal tissues. We undertook a study in patients treated with preoperative
      radiotherapy and demonstrated in vivo the importance of proliferation, migration,
      and fibrogenic phenotype of vascular smooth muscle cells (VSMCs) in radiation
      induced vascular damage. These lesions may result from imbalance in the cross
      talk between endothelial cells (ECs) and VSMCs. Using co-culture models, we
      examined whether ECs influence proliferation, migration, and fibrogenic phenotype
      of VSMCs. In the presence of irradiated ECs, proliferation and migration of VSMCs
      were increased. Moreover, expressions of alpha-smooth muscle actin, connective
      tissue growth factor, plasminogen activator inhibitor type 1, heat shock protein
      27, and collagen type III, alpha 1 were up-regulated in VSMCs exposed to
      irradiated ECs. Secretion of transforming growth factor (TGF)-beta1 was increased
      after irradiation of ECs, and irradiated ECs activated the Smad pathway in VSMCs
      by inducing Smad3/4 nuclear translocation and Smad-dependent promoter activation.
      Using small interferring RNA targeting Smad3 and a TGFbeta-RII neutralizing
      antibody, we demonstrate that a TGF-beta1/TGF-beta-RII/Smad3 pathway is involved
      in the fibrogenic phenotype of VSMCs induced by irradiated ECs. In conclusion, we
      show the importance of proliferation, migration, and fibrogenic phenotype of
      VSMCs in patients. Moreover, we demonstrate in vitro that ECs influence these
      fundamental mechanisms involved in radiation-induced vascular damages.

PMID- 17003502
TI  - Vascular endothelial growth factor-A mediates ultraviolet B-induced impairment of
      lymphatic vessel function.
AB  - UVB irradiation of the skin induces erythema, epidermal hyperplasia, vascular
      hyperpermeability, and edema formation. Previous studies have revealed that the
      cutaneous blood vasculature plays a critical role in the mediation of
      photodamage. In contrast, the role of lymphatic vessels, which play an essential
      role in the maintenance of tissue fluid balance, in the response to UVB
      irradiation has remained unknown. We report here that both acute and chronic UVB
      irradiation of murine skin results in prominent enlargement of lymphatic vessels.
      Surprisingly, these enlarged lymphatic vessels were functionally impaired and
      hyperpermeable, as detected by intravital lymphangiography. The expression levels
      of vascular endothelial growth factor (VEGF)-A but not of the known
      lymphangiogenesis factors VEGF-C or VEGF-D, were enhanced in UVB-irradiated
      epidermis. Targeted overexpression of VEGF-A in the epidermis of transgenic mice
      led to increased enlargement and leakage of lymphatic vessels after acute UVB
      irradiation, whereas systemic blockade of VEGF-A signaling largely prevented
      lymphatic vessel abnormalities and photodamage induced by UVB. Together, these
      findings identify lymphatic vessels as novel targets for UVB-induced cutaneous
      photodamage and suggest that VEGF-A mediates impairment of lymphatic vessel
      function, thereby contributing to the adverse effects of UVB irradiation on the
      skin.

PMID- 17003504
TI  - Elovl3: a model gene to dissect homeostatic links between the circadian clock and
      nutritional status.
AB  - The ELOVL3 protein is a very long-chain fatty acid elongase found in liver, skin,
      and brown adipose tissues. Circadian expression of the Elovl3 gene in the liver
      is perturbed in mutant CLOCK mice but persists in mice with severe hepatic
      dysfunction. A reliance on an intact clock, combined with the refractoriness to
      liver decompensation and the finding of a robust sexually dimorphic pattern of
      expression, evince a particularly complex mode of transcriptional control. The
      Elovl3 gene upstream region was repressed by RevErbalpha and activated by sterol
      regulatory element binding protein-1 (SREBP1) transcription factors. We propose
      that the temporal coordination of RevErbalpha and SREBP1 activities integrates
      clock and nutrition signals to drive a subset of oscillatory transcripts in the
      liver. Proteolytic activation of SREBP1 is circadian in the liver, and because
      the cycle of SREBP1 activation was reversed after restricting meals to the
      inactive phase of the day, this factor could serve as an acute sensor of
      nutritional state. SREBP1 regulates many known lipogenic and cholesterogenic
      circadian genes; hence, our results could explain how feeding can override brain
      derived entraining signals in the liver. This mechanism would permit a rapid
      adjustment in the sequence of key aspects of the absorptive and postabsorptive
      phases in the liver.

PMID- 17003505
TI  - Signaling pathways influencing SLF and c-kit-mediated survival and proliferation.
AB  - Steel factor (SLF) and c-Kit are a ligand-receptor pair that regulates growth and
      activation of a variety of hemopoietic and non-hemopoietic cells. This review
      describes our work investigating downstream signaling pathways activated by SLF,
      with particular emphasis on signaling differences associated with soluble vs
      membrane- bound ligand, and our identification of an important role for PLC
      activation and Ca2+ influx in supporting c-Kit positive cells in vitro and in
      vivo. This work led to the identification of a unique form of cell death termed
      activation enhanced cell death (AECD) that involves stimulating a cell with a
      growth or activation signal while concurrently blocking Ca2+ influx. Approaches
      that we have taken toward identifying cellular factors associated with
      sensitivity and resistance to AECD are summarized, as is our experience with a
      variety of experimental models. The use of econazole as a calcium channel blocker
      and its mechanism of action are described, as is its potential for development as
      an anticancer therapeutic.

PMID- 17003506
TI  - NKR-P1 biology: from prototype to missing self.
AB  - Natural killer (NK) cells represent lymphocytes of the innate immune system
      capable of recognizing and destroying a broad array of target cells, including
      tumors, virus-infected cells, antibodycoated cells, foreign transplants, and
      "stressed" cells. NK cells eliminate their targets through two main effector
      mechanisms, cytokine secretion and cell-mediated cytotoxicity, which in turn
      depend on detection of target cells through a complex integration of stimulatory
      and inhibitory receptor-ligand interactions. The NKR-P1 molecules were the first
      family of NK cell receptors identified, yet they have remained enigmatic in their
      contribution to self-nonself discrimination until recently. Here, we outline a
      brief history of the NKR-P1 receptor family, then examine recent data providing
      insight into their genetic regulation, signaling function, cognate ligands, and
      gene organization and diversity.

PMID- 17003507
TI  - Interferons and viruses: signaling for supremacy.
AB  - Interferon (IFN)-alpha and IFN-beta are critical mediators of host defense
      against microbial challenges, directly interfering with viral infection and
      influencing both the innate and adaptive immune responses. IFNs exert their
      effects in target cells through the activation of a cell-surface receptor,
      leading to a cascade of signaling events that determine transcriptional and
      translation regulation. Understanding the circuitry associated with IFN-mediated
      signal transduction that leads to a specific biological outcome has been a major
      focus of our laboratory. Through the efforts of graduate students, postdoctoral
      fellows, a skilled research technologist, and important collaborations with
      investigators elsewhere, we have provided some insights into the complexity of
      the IFN system-and the elegance and simplicity of how protein-protein
      interactions define biological function.

PMID- 17003508
TI  - The lymphotoxin pathway: beyond lymph node development.
AB  - The first studies of mice deficient in lymphotoxin-alpha (LTalpha), LTbeta and
      LTbetaR revealed the seminal discovery that the LTbetaR signaling is critical for
      the development of lymph nodes and Peyer's patches during embryogenesis. Since
      these initial findings, it is increasingly appreciated that signaling through the
      lymphotoxin-beta receptor (LTbetaR) plays a key role in numerous biological
      processes in the adult animal, including the maintenance of specialized stromal
      cell types and the homeostatic control of chemokine expression within the
      lymphoid tissues. A major focus of our laboratory is to understand the relevance
      of LTbetaR signaling in initiating immune responses both dependent and
      independent of its role in maintaining the organization of lymphoid tissues. This
      review will therefore explore new possibilities for how this complex pathway
      regulates humoral and cellular immunity.

PMID- 17003509
TI  - Lymph, lymphocytes, and lymphatics.
AB  - This is a summary of recent developments regarding the role of the lymphatic
      system in immune responses. Emphasis is on physiological considerations from
      experiments in sheep. Cell- and tissue-specific lymphocyte traffic patterns
      measured over several days are considered. Particular attention is given to
      recent data on the relationship between the central nervous system and the
      lymphatic system, to cell labeling in situ, and to the entry of immune cells into
      afferent lymph from the interstitial tissues.

PMID- 17003510
TI  - Leukocyte-specific protein 1 (LSP1): a regulator of leukocyte emigration in
      inflammation.
AB  - LSP1 is an F-actin bundling cytoskeletal protein expressed in hematopoietic
      lineage and endothelial cells. We investigated the function of this protein by
      generating and analyzing an LSP1-deficient mouse strain and in this review we
      describe our findings together with those of other investigators. The results
      show a complex function of LSP1 in regulating leukocyte recruitment to inflamed
      sites. Based on current evidence, we propose that the levels of LSP1 on the
      cytoskeleton and the type of integrin involved are some of the critical elements
      which affect LSP1 function in modulating the threshold for transmigration.

PMID- 17003512
TI  - Why can't the immune system control HIV-1? Defining HIV-1-specific CD4+ T cell
      immunity in order to develop strategies to enhance viral immunity.
AB  - Globally, at least 60 million people have been infected with the human
      immunodeficiency virus type 1 (HIV-1), the majority of whom will develop the
      acquired immunodeficiency syndrome (AIDS) leading to tremendous morbidity and the
      mortality. Understanding the immunopathogenesis of AIDS and the immune correlates
      of viral protection are necessary to develop effective vaccines and
      immunotherapies. A major focus of our laboratory has been to understand the CD4+
      T cell immune response directed against HIV- 1, and to determine mechanisms of T
      cell dysfunction that lead to viral escape. In addition, we are interested in
      evaluating the TNF-TNFR family members as potential molecular adjuvants that
      could be incorporated into vaccines which could be used to further boost T cell
      immunogenicity in healthy or HIV-1-infected individuals, as many of these
      molecules have been shown to replace the functions of CD4+ T cell help.

PMID- 17003511
TI  - Antibody diversification: mutational mechanisms and oncogenesis.
AB  - Antibody diversification processes play a major role in protecting humans from
      pathogens. Somatic hypermutation and gene conversion increase the affinity of
      pathogen-specific antibodies by changing the sequence within antibody variable
      genes, while the class switch recombination (CSR) process changes the antibody's
      effector function by replacing the constant region of the antibody gene with a
      different constant region. Activation-induced cytidine deaminase (AID) initiates
      each of these three processes by deaminating cytidines within antibody genes,
      while a host of other DNA transacting factors are involved in either creating new
      mutations or repairing DNA lesions introduced during these processes. This review
      will discuss the main features of antibody diversification and their role in
      lymphomagenesis, highlight outstanding issues and questions that remain in the
      field, and discuss our contributions to this field.

PMID- 17003513
TI  - Ligand-independent signaling during early avian B cell development.
AB  - Surface immunoglobulin (sIg) expression has been conserved as a critical
      checkpoint in B lymphocyte development. In the chicken embryo, only sIg+ B cells
      are selectively expanded in the bursa of Fabricius, a primary lymphoid organ
      unique to the avian species. We have previously demonstrated that an interaction
      between the antigen- binding sites of sIg and a specific bursal ligand(s) is not
      required to regulate this developmental checkpoint. Rather, the requirement for
      sIg expression can be attributed to the surface expression of the Igalpha/beta
      heterodimer associated with sIg. More specifically, ligand-independent signaling
      downstream of the Igalpha cytoplasmic domain drives all bursal stages of B cell
      development during embryogenesis. We discuss here a site-directed mutagenesis
      approach to identify the critical membrane proximal events involved in ligand
      independent signaling during B cell development.

PMID- 17003514
TI  - Human T cell immunodeficiency: when signal transduction goes wrong.
AB  - Severe combined immunodeficiency (SCID) is a heterogeneous group of diseases that
      are invariably fatal in infancy unless treated by hematopoietic stem cell
      replacement. For many years we have worked to better manage patients affected by
      SCID through rapid and accurate diagnosis followed by treatment aimed at
      achieving long-lasting immune reconstitution. By extensive immunological,
      biochemical, and genetic studies of patient samples, and with the realization of
      differences between human and murine T cell development, we have successfully
      been able to identify some of the molecular defects causing SCID. Among these
      discoveries, we described the first mutated signal transduction protein in T
      cells (ZAP-70); the first genetic defect leading to SCID and autoimmune phenomena
      (IL2R alpha); and, recently, the critical importance of CD3delta in the
      development of T cells. Our efforts have significantly advanced the understanding
      of the role of some of the signal-transducing proteins in T cell maturation and
      function. This review summarizes several of these discoveries and some of their
      impact on our understanding of T cells development, function, and homeostasis in
      humans.

PMID- 17003515
TI  - Investigations into the regulation and function of the SH2 domain-containing
      protein-tyrosine phosphatase, SHP-1.
AB  - Our laboratory is interested in identifying genes relevant to diseases. Our
      approach is to use spontaneous mouse mutants with immunological defects and
      decipher the molecular basis of the phenotypes. In the early 1990s, our attention
      was focused on the motheaten and viable motheaten mouse mutants. We used these
      mutant mice as a model system for elucidating the genetic and cellular events
      contributing to expression of normal hematopoietic and immune function. Our
      initial goal was to identify the gene responsible for the motheaten and viable
      motheaten phenotype. In 1993, we and others reported that both motheaten and
      viable motheaten mice have mutations in the SHP-1 gene. Currently, there are more
      than 600 publications involving SHP-1. In this review, rather than summarizing
      all these studies, we highlight work involving SHP-1 that were/are carried out in
      our and our collaborators' laboratories.

PMID- 17003516
TI  - Approaches to studying costimulation of human antiviral T cell responses:
      prospects for immunotherapeutic vaccines.
AB  - The generation of strong and specific CD8 T cell responses is important in the
      control of viral infections. Costimulatory molecules provide signals necessary
      for the development or maintenance of these responses. A major focus of our
      laboratory is to investigate the role of costimulatory molecules of the TNFR and
      CD28 families in antiviral responses. Our aim is to translate information
      obtained using murine models to the study of these molecules using human cells.
      We have devised an in vitro system using recombinant replication- deficient
      adenovirus to deliver costimulatory molecules to antigen-presenting cells that
      are then used to stimulate autologous T cells from both healthy and HIV-infected
      individuals. Here we describe our findings and discuss the implications of
      incorporating costimulatory molecules into viral vector vaccine strategies.

PMID- 17003517
TI  - Assembly of MHC class I molecules within the endoplasmic reticulum.
AB  - MHC class I molecules bind cytosolically derived peptides within the endoplasmic
      reticulum (ER) and present them at the cell surface to cytotoxic T cells. A major
      focus of our laboratory has been to understand the functions of the diverse
      proteins involved in the intracellular assembly of MHC class I molecules. These
      include the molecular chaperones calnexin and calreticulin, which enhance the
      proper folding and subunit assembly of class I molecules and also retain assembly
      intermediates within the ER; ERp57, a thiol oxidoreductase that promotes heavy
      chain disulfide formation and proper assembly of the peptide loading complex;
      tapasin, which recruits class I molecules to the TAP peptide transporter and
      enhances the loading of high affinity peptide ligands; and Bap31, which is
      involved in clustering assembled class I molecules at ER exit sites for export
      along the secretory pathway. This review describes our contributions to
      elucidating the functions of these proteins; the combined effort of many
      dedicated students and postdoctoral fellows.

PMID- 17003518
TI  - Double-negative regulatory T cells: non-conventional regulators.
AB  - The crucial role of regulatory T (Treg) cells in self-tolerance and
      downregulating immune responses has been clearly established. Numerous different
      Treg subsets have been identified that possess distinct phenotypes and functions
      in various disease models. Among these subsets, alphabeta-TCR+CD3+CD4-CD8- double
      negative (DN) Treg cells have been shown to be able to inhibit a variety of
      immune responses in part via direct killing of effector T cells in an
      antigenspecific manner in both mice and humans. This was shown to occur at least
      partially by acquisition of MHC-peptide complexes from antigen-presenting cells
      (APCs) and subsequent Fas/Fas-ligand interactions. In addition, DN Treg cells
      have been shown to express several molecules uncommon to other Treg cell subsets,
      such as IFN-gamma, TNF-alpha, Ly6A, FcRgamma, and CXCR5, which may contribute to
      their unique regulatory ability. Understanding the development and regulatory
      functions of DN Treg cells may elucidate the etiology for loss of self-tolerance
      and serve as a therapeutic modality for various diseases. This review will
      summarize the characteristics, developmental pathways, and mechanisms of action
      of DN Treg cells, as well as their role in transplant tolerance, autoimmunity,
      and anticancer immunity.

PMID- 17003521
TI  - Cellular and molecular alterations in mice with deficient and reduced serotonin
      transporters.
AB  - The function of serotonin transporters (SERTs) is related to mood regulation.
      Mice with deficient or reduced SERT function (SERT knockout mice) show several
      behavioral changes, including increased anxiety-like behavior, increased
      sensitivity to stress, and decreases in aggressive behavior. Some of these
      behavioral alterations are similar to phenotypes found in humans with short
      alleles of polymorphism in the 5-hydroxytryptamine (5-HT) transporter-linked
      promoter region (5-HTTLPR). Therefore, SERT knockout mice can be used as a tool
      to study 5-HTTLPR-related variations in personality and may be the etiology of
      affective disorders. This article focuses on the cellular and molecular
      alterations in SERT knockout mice, including changes in 5-HT concentrations and
      its metabolism, alterations in 5-HT receptors, impaired hypothalamic-pituitary
      adrenal gland axis, developmental changes in the neurons and brain, and influence
      on other neurotransmitter transporters and receptors. It also discusses the
      possible relationships between these alterations and the behavioral changes in
      these mice. The knowledge provides the foundation for understanding the cellular
      and molecular mechanisms that mediate the SERT-related mood regulation, which may
      have significant impact on understanding the etiology of affective disorders and
      developing better therapeutic approaches for affective disorders.

PMID- 17003519
TI  - Neuronal activity: from in vitro preparation to behaving animals.
AB  - The knowledge of the mechanisms regulating electric neuronal activity is
      fragmented by the wide variety of techniques and experimental models currently
      used in neurophysiological research. The interest and importance of the results
      obtained in any research is improved when interpreted in the perspective of the
      organism functioning as a whole in physiological conditions. Such interpretation,
      freed of the constraints imposed by the different techniques and experimental
      conditions used, is especially important when discussing together results
      obtained at the behavioral, cellular, and molecular level. This article outlines
      some of the key factors to consider when experiments from different models are
      interpreted together.

PMID- 17003520
TI  - Interplay between the p53 tumor suppressor protein family and Cdk5: novel
      therapeutic approaches for the treatment of neurodegenerative diseases using
      selective Cdk inhibitors.
AB  - Cyclin-dependent kinases (Cdks) play a key role in orchestrating the coordination
      of cell cycle progression in proliferating cells. The escape from the proper
      control of the cell cycle by the upregulation of cyclins or aberrant activation
      of Cdks leads to malignant transformation. In quiescent cells and/or terminally
      differentiated cells, the expression pattern and activity of Cdks is altered. In
      postmitotic neurons, expression of mitotic kinases is downregulated, whereas Cdk5
      expression becomes upregulated. Similarly to other Cdks, free Cdk5 displays no
      enzymatic activity and requires complex formation with a specific regulatory
      subunit. Two activators of Cdk5 have been identified. p35 and its isoform p39
      bind to, and thereby activate, Cdk5. Unlike mitotic kinases, Cdk5 does not
      require activating phosphorylation within the T-loop. Because p35 is a short
      lived protein, the p35/Cdk5 complexes are unstable. The stability of the p35
      protein is regulated by its Cdk5-mediated phosphorylation of p35. Activated
      p35/Cdk5 kinase phosphorylates numerous physiological targets. The proper
      phosphorylation of the most important substrates, such as tau protein and
      neurofilament H, is essential for the correct regulation of the cytoskeletal
      organization, thereby regulating cell adhesion, motility, and synaptic
      plasticity. Moreover, Cdk5 regulates the activity of the p53 tumor suppressor via
      phosphorylation. p53 is upregulated in multiple neuronal death paradigms,
      including hypoxia, ischemia, and excitotoxicity, and plays a key role in the
      induction of apoptosis. On the other hand, an abnormally high expression and
      elevated activity of Cdk5 was observed in neurodegenerative diseases, suggesting
      the application of Cdk inhibitors for their therapy. Considering the action of
      some Cdk inhibitors on the expression and activity of the p53 protein, their
      therapeutic efficacy must be carefully evaluated.

PMID- 17003523
TI  - Abstracts from the Italian Association for the Study of the Pancreas (AISP) 30th
      National Congress. Milan, Italy. September 21-23, 2006.

PMID- 17003522
TI  - Central nervous system functions of PAK protein family: from spine morphogenesis
      to mental retardation.
AB  - Several of the genes currently known to be associated, when mutated, with mental
      retardation, code for molecules directly involved in Rho guanosine triphosphatase
      (GTPase) signaling. These include PAK3, a member of the PAK protein kinase
      family, which are important effectors of small GTPases. In many systems, PAK
      kinases play crucial roles regulating complex mechanisms such as cell migration,
      differentiation, or survival. Their precise functions in the central nervous
      system remain, however, unclear. Although their activity does not seem to be
      required for normal brain development, several recent studies point to a possible
      involvement in more subtle mechanisms such as neurite outgrowth, spine
      morphogenesis or synapse formation, and plasticity. This article reviews this
      information in the light of the current knowledge available on the molecular
      characteristics of the different members of this family and discuss the
      mechanisms through which they might contribute to cognitive functions.

PMID- 17003524
TI  - Enhanced sequence coverage in tryptic fragment analysis by two-dimensional
      HPLC/MS using a monolithic silica capillary column.
AB  - The HPLC/MS system, in which a monolithic silica capillary column is directly
      connected to an electronspray-ionization mass spectrometer, showed superior
      performance at high mobile phase linear velocity. A two-dimensional (2D) HPLC/MS
      system was established, using an ion-exchange particle-packed capillary column at
      the first dimension and a monolithic silica capillary column at the second
      dimension. In an analysis of tryptic fragments from bovine serum albumin, an 81%
      sequence coverage, obtained by the 2D-HPLC/MS system, increased by 23% as
      compared to a 1D-HPLC/MS system. This 2D-HPLC/MS system using a monolithic silica
      capillary column should be useful for enhancing sequence coverage of tryptic
      fragments in proteomics.

PMID- 17003525
TI  - An asian woman with eosinophilia and bilateral pulmonary infiltrates.

PMID- 17003526
TI  - Diffuse cystic disease of the lung associated with simultaneous bilateral
      spontaneous pneumothorax: an unknown component of Caroli disease?
AB  - Simultaneous bilateral spontaneous pneumothorax is an uncommon and serious
      medical problem frequently related to an underlying lung disease such as
      parenchymal lung disease, inflammatory events or neoplasms. Recurrent
      pneumothorax associated with persistent air leakage may pose a therapeutic
      dilemma in patients with underlying lung diseases. Caroli disease (CD) is a very
      rare congenital disorder characterised by intrahepatic biliary cystic dilatations
      and frequently associated with polycystic kidney and hepatic fibrosis. To date,
      no relation between CD and the bilateral diffuse cystic structure of pulmonary
      parenchyma has been described. In this paper we present a patient with the
      diagnosis of CD in whom simultaneous bilateral spontaneous pneumothorax was the
      initial finding due to severe underlying pulmonary disease. Our patient's
      demographic and clinical characteristics, laboratory findings and course made us
      exclude the other aetiologies leading to such diffuse multi-bullous pulmonary
      involvement. The coincidence of recurrent pneumothorax and severe pulmonary
      disease has led to a big therapeutic dilemma. Open or minimally invasive surgery
      could be morbid or even mortal because of the nature of the parenchyma and the
      operative risk due to CD. Therefore, we suggest a unique conservative management
      including tube thoracostomy by locating the correct air spaces with the aid of
      high-resolution computed tomography followed by talc pleurodesis in patients with
      severe multi-bullous lung disease associated with potential risks due to co
      morbidities.

PMID- 17003527
TI  - Itraconazole comedication increases systemic levels of inhaled fluticasone in
      lung transplant recipients.
AB  - BACKGROUND: After lung transplantation (LTx), inhaled corticosteroids may be
      prescribed and at the same time prophylaxis against fungal infections with
      itraconazole is common. In our center, the addition of inhaled fluticasone
      propionate to systemic immunosuppression resulted in clinical Cushing's syndrome
      in 4 lung transplant recipients on itraconazole comedication. OBJECTIVES: The
      current study was undertaken to compare systemic levels of inhaled fluticasone in
      patients with and without concomitant itraconazole therapy. METHODS: The single
      center, prospective controlled study was performed in the LTx program in Zurich,
      Switzerland. Twenty stable recipients, 1-7 years after LTx, on a prednisone
      maintenance dose (5-7.5 mg/day) gave informed consent and were assigned to 2
      groups: (A) without itraconazole comedication and (B) currently on itraconazole,
      being continued during the study period. The patients of both groups started
      inhalation of 1 mg fluticasone propionate twice daily for 14 days with a powder
      disc inhaler. Plasma fluticasone levels were measured before the start of the
      study and on day 14. RESULTS: Fluticasone levels before starting the treatment
      were below the detection limit in all 17 patients (7 in group A and 10 in group
      B) adhering to the study protocol. Baseline characteristics (underlying disease,
      age at LTx, time since LTx, FEV(1)) were comparable between the 2 groups. On
      study day 14, plasma fluticasone levels had increased to detectable levels in all
      patients (A: 273 +/- 124 pg/ml, B: 701 +/- 131 pg/ml), i.e. to significantly
      higher (p = 0.038) concentrations in patients on itraconazole. CONCLUSIONS:
      Itraconazole comedication substantially increases systemic levels of inhaled
      fluticasone, most likely by inhibiting the cytochrome P450 3A4 enzyme system and
      thus the clearance of fluticasone. Accumulation of fluticasone can result in
      increased systemic effects and therefore comedication has to be taken into
      consideration when inhaled fluticasone is prescribed.

PMID- 17003528
TI  - Recent clinical advances in the management of critically ill patients with acute
      renal failure.
AB  - BACKGROUND: Significant progress has been made in the field of renal replacement
      therapy for critically ill patients with acute renal failure (ARF) over the past
      few years. This review highlights these developments. METHODS: Recent studies
      assessing the clinical utility of the RIFLE classification system for the
      diagnosis of ARF were reviewed. Clinical outcome studies evaluating the effect of
      continuous renal replacement therapy (CRRT) dose and timing of initiation were
      assessed. The final review topic was the effect of dialysis modality on the
      recovery of renal function in ARF patients. CONCLUSIONS: Based on recent clinical
      studies, the increasing use of the RIFLE criteria is justified, as this approach
      appears to be a robust method for both the diagnosis of and prognostication in
      ARF. A large randomized trial involving convective CRRT supports the commonly
      used prescription of 35 ml/ kg/h in clinical practice. Moreover, numerous recent
      outcome studies, also largely involving convective CRRT, provide a clinical
      rationale for the increasingly common clinical practice of earlier initiation.
      Finally, several recent studies suggest CRRT, relative to conventional
      hemodialysis, results in a greater rate of renal recovery in ARF patients.

PMID- 17003530
TI  - Genetic education for non-geneticist health professionals.
AB  - OBJECTIVES: It was the aim of this study to assess educational needs and
      priorities in genetics amongst non-genetic health professionals. METHODS: The
      methods used included website reviews and direct contact with individuals and
      organisations involved in health professional education. RESULTS AND CONCLUSIONS:
      Health professional education and training differed in structure with wide
      variation in the content and duration of genetics education provided. Evidence
      from the UK, France and Germany indicates that genetics professionals are
      influencing the genetics content of medical curricula. In post-graduate training,
      some specialist regulators have adopted specific genetics education requirements,
      but many programmes lack any explicit genetics. We show that within each country,
      a sometimes confusing plethora of organisations has responsibility for setting,
      assessing and delivering medical and midwifery education.

PMID- 17003531
TI  - France: genetics education for non-genetics health care providers.
AB  - OBJECTIVE: This paper explores the treatment of medical genetics in undergraduate
      medical education, specialists' training and continuing medical education (CME)
      for general practitioners, specialists, nurses and midwives. METHODS: We
      conducted a qualitative survey of websites, published or unpublished documents,
      telephone interviews and mailed questionnaires. RESULTS: Genetics is a medical
      specialty in France, and the small number of university professors in genetics
      are in charge of the genetic component of medical training of all future
      practitioners. The study was complicated by the ongoing waves of reforms in the
      French health and educational systems and by the autonomy of the faculties.
      Specialist training and CME in genetics is heterogeneous and not organised as a
      priority. CONCLUSIONS: Specialist education and CME in genetics of non-geneticist
      health care providers needs to be adapted to the fast ongoing developments of
      this field of knowledge.

PMID- 17003532
TI  - Education in medical genetics for physicians: Germany.
AB  - We have assessed the relative amount of genetics education at each of the 3
      levels of medical training in Germany, namely the undergraduate, postgraduate and
      continuous medical education stages. Our data show that genetics is ill
      represented at all levels. Written examinations at the end of the relevant
      section at the undergraduate level include very few questions related to medical
      genetics, and particularly few in subjects such as pathology, internal medicine
      and gynaecology and obstetrics. At the postgraduate level, only 4 specialties
      require knowledge in medical genetics that may be subject to examination. At the
      continuous medical education level, medical genetics plays a very minor role. All
      3 levels have been subject to reform in recent years, but effects that might
      ensue from these reforms cannot be expected before 2008.

PMID- 17003533
TI  - Education in medical genetics for non-genetic health care providers in Sweden.
AB  - We investigated the content and extent of education in medical/clinical genetics
      among Swedish universities, university colleges and colleges of health providing
      undergraduate education for medical doctors and nurses. In addition, selected
      medical specialist training programmes and programmes for midwives and district
      nurses were analysed to detect elements of education or training in
      medical/clinical genetics. The main results are that, although basic cell biology
      is taught during the first semesters in all education, there is little or no
      genetics taught during the clinical parts of the educational programmes.
      Moreover, with regard to post-graduate education, it is almost absent. There is a
      need to improve education and training in genetics for all health care
      professionals to meet the expected increase in genetic issues in clinical
      medicine.

PMID- 17003534
TI  - Genetics education for non-genetic health care professionals in the Netherlands
      (2002).
AB  - OBJECTIVE: The aim of the present study was to investigate whether medical care
      providers in the Netherlands are adequately educated in genetics by collecting
      information about the current state of genetics education of non-genetics health
      care professionals. METHOD: The curricula of the 8 universities providing medical
      education and of all varieties of specialised medical training were examined for
      the year 2002. RESULTS: In most universities, the number of hours spent on
      genetics education is small, and genetics is relatively invisible, being
      integrated within several courses, comprising only a small proportion of the
      total course (a mean of 8%). Only 3 of the programmes for medical specialist
      training and the training of medical doctors for mentally handicapped people
      indicated a formal genetics education programme. Continued education courses on
      genetics are offered irregularly. Training in midwifery involves at least 3 weeks
      of genetics education. Courses on genetics are offered frequently to practicing
      midwives. CONCLUSION: There appear to be no general, nationally defined final
      goals for education in genetics for non-genetics health care professionals in the
      Netherlands. Furthermore, the lack of visibility of genetics in medical education
      in the Netherlands was striking.

PMID- 17003535
TI  - Genetics teaching for non-geneticist health care professionals in the UK.
AB  - OBJECTIVES: It was the aim of this study to describe the structure and content of
      training in genetics for non-genetics specialist health care professionals in the
      UK. METHODS: Data were collected by assessment of published syllabi and curricula
      and through contact with educational leads at responsible organisations. RESULTS:
      Twenty-six universities, 7 Royal Colleges and various intercollegiate boards and
      committees are involved in the provision of medical education at various levels,
      in addition to institutions offering nursing and/or midwifery training. Genetics
      is taught in variable formats, quantities and contents, and although some
      institutions are moving to adopt minimum competencies in genetics, this is by no
      means widespread. CONCLUSIONS: Given the wide number of stakeholders in the
      field, consensus competencies seem most likely to advance practice, and thus,
      phase II of the GenEd project will survey professionals to ascertain their
      priorities for genetic education.

PMID- 17003536
TI  - Understanding the information needs of general practitioners managing a rare
      genetic disorder (osteogenesis imperfecta).
AB  - BACKGROUND: Lack of adequate knowledge is a common problem in medicine, but is a
      particular problem in a rapidly advancing field like genetics. This study uses
      the example of a rare genetic disorder (osteogenesis imperfecta) to understand
      the information needs of primary care physicians (GPs). OBJECTIVES: To determine
      whether a knowledge gap is recognised, how GPs currently attempt to overcome it,
      and what features of an information resource are preferred by GPs. METHODS: GPs
      of children affected by osteogenesis imperfecta in and around Greater London were
      interviewed, using both questionnaire-based semi-structured interview and a
      qualitatively analysed open-ended discussion. Consultations in both primary and
      tertiary care settings over a 5-year period were compared. RESULTS: Problems due
      to osteogenesis imperfecta were presented to GPs in about one third of
      consultations with these patients. GPs reported finding such patients difficult
      to manage due to lack of knowledge. Knowledge from tertiary sources, which was
      authoritative, accessible and relevant, was preferred, particularly when
      reasoning was explained. Primary literature and clinical guidelines were not
      favoured. CONCLUSIONS: Empirical evidence supports and elaborates theoretical
      models for provision of clinically useful information. A model for improved
      information services using authoritative web-based information linked to
      electronic patient records is suggested.

PMID- 17003537
TI  - Genetics and congenital malformations: interpretations, attitudes and practices
      in suburban communities and the shamans of ecuador.
AB  - OBJECTIVES: The purpose of the present article was to evaluate how shamans and
      the suburban communities of Quito interpret the terminology used in genetics.
      METHODS: One hundred people living in 5 suburban districts of Quito were surveyed
      as well as 19 shamans of the Salasaca community. RESULTS: The results show that
      members of both groups are little informed about genetics. As knowledge about
      genetics is correlated to educational level, which is very poor in both groups,
      knowledge and understanding of genetics are either very basic or nonexistent. As
      for the medical practices in treating genetic alterations, the surveys show that
      while in very severe cases scientific medicine is sought, in most cases
      explanations and a cure are given by shamanic medicine. CONCLUSION: There is
      limited knowledge of genetics and its terminology in the study population.
      Shamanic and marginal health practices seem to remain prevalent in these
      communities due to their low costs, the personal attention the individuals
      receive, and the holistic point of view employed. It is important that the
      community councils, the medical doctors and the shamans work together to set up
      community programs on medical education, particularly on genetics.

PMID- 17003538
TI  - 'Genetics home reference': helping patients understand the role of genetics in
      health and disease.
AB  - The surge of information generated by the Human Genome Project has left many
      health professionals and their patients struggling to understand the role of
      genetics in health and disease. To aid the lay public and health professionals,
      the US National Library of Medicine developed an online resource called 'Genetics
      Home Reference' (GHR), located at http://ghr.nlm.nih.gov/. Launched in April
      2003, GHR's goal is to help the public interpret the health implications of the
      Human Genome Project. It bridges the clinical questions of consumers and the rich
      technical data emerging from the sequenced human genome. The GHR web site is
      designed for easy navigation among summaries for genetic conditions and the
      related gene(s) and chromosome(s). This design strategy enhances the user's
      appreciation of how genes, chromosomes, and conditions are interrelated.

PMID- 17003539
TI  - What role for public health in genetics and vice versa?

PMID- 17003541
TI  - Complete resolution of acute renal failure after left renal artery angioplasty
      and stent placement for total renal artery occlusion.
AB  - A 25-year-old female, 17 weeks pregnant presented to our hospital with complaints
      of progressively increasing dyspnea. She was hypertensive with creatine of 1.0;
      she was transferred to ICU with multiple medications to control her blood
      pressure, without success. The patient continued to decompensate, which required
      intubation. The patient developed acute renal failure, part of her work-up
      suggested bilateral renal artery stenosis. She was taken to the catheterization
      lab and was found to have bilateral total renal artery occlusion. The left renal
      artery was successfully opened. The patient recovered and her blood pressure was
      controlled after the procedure. In the past, surgery was the preferred treatment
      in cases of acute renal artery occlusion. This approach has been replaced
      increasingly by renal artery angioplasty, which is less invasive and is at least
      as effective as surgical reconstruction. Our case demonstrates a percutaneous
      approach can be tried for totally occluded renal artery with a successful
      outcome.

PMID- 17003542
TI  - Weekly variation of the QT dispersion in healthy subjects and in patients with
      coronary heart disease.
AB  - BACKGROUND: A circadian and seasonal variation of QT dispersion (QTd) has been
      shown in healthy individuals. Nevertheless, no data exist regarding the weekly
      influences on the QTd in healthy individuals and in patients with coronary heart
      disease (CHD). DESIGN: This study was designed to determine whether there is a
      weekly variability of QTd in healthy individuals and in patients with CHD.
      METHODS: In this prospective registry study, 53 patients with documented CHD and
      57 healthy control subjects were involved. Resting electrocardiograms (ECGs) with
      double amplitude were recorded at a speed of 50 mm/s on Monday and Friday
      mornings. QT intervals were measured and QTd were determined by calculating the
      difference between maximum and minimum QT intervals. Then, rate-corrected QTd
      (QTcd) were calculated using Bazett's formula. RESULTS: There was a significant
      weekly variation of QTd in control subjects (39.3 +/- 6.3 vs. 36.2 +/-6.1 ms) (p
      < 0.05) and in patients (56 +/- 7.3 vs. 47.4 +/- 5.4 ms) (p < 0.0001). There was
      also a significant weekly variation of QTcd both in control subjects (33 +/- 5.3
      vs. 30.7 +/- 5.6 ms) (p < 0.05) and in patients (47.4 +/- 6.4 vs. 41.9 +/- 5.4
      ms) (p < 0.0001). CONCLUSIONS: There is a weekly variation of QTd and QTcd in
      healthy individuals and in patients with CHD, both with a Monday preference. This
      fact should be taken into consideration during the chronopharmacological
      treatment or advisal of primary or secondary preventive measures to these
      subjects or patients.

PMID- 17003543
TI  - Left ventricular diastolic dysfunction is related to oxidative stress and
      exercise capacity in hypertensive patients with preserved systolic function.
AB  - BACKGROUND: Left ventricular diastolic dysfunction and oxidative stress are
      important determinants in heart failure development. Peak oxygen uptake, maximal
      oxygen consumption, metabolic equivalents (MET), ventilatory response and time to
      respiratory gas exchange assess cardiopulmonary capacity. AIM: It was the aim of
      this study to investigate the impact of oxidative stress on diastolic indexes and
      cardiopulmonary exercise capacity in hypertensive patients with left ventricular
      diastolic dysfunction. METHODS: Mitral flow velocities (E, A), ejection fraction,
      left atrial and ventricular diameters were assessed by Doppler echocardiography.
      Superoxide dismutase (SOD) and glutathione peroxidase activity in blood were
      evaluated. Sixty patients (aged 49.8 +/- 9.2 years) with essential hypertension
      and preserved systolic function (ejection fraction 58.3 +/- 7%) performed a
      bicycle exercise test. Forty patients showed impaired left ventricular relaxation
      (E/A <1, deceleration time of E >220 ms) and were assigned to group 1, while 20
      had normal relaxation (group 2). RESULTS: An increase in SOD was significantly
      blunted after exercise in group 1 compared with group 2 (p = 0.049). A
      significant difference between groups in the glutathione peroxidase level was
      observed before exercise (p = 0.038). There were significantly lower values of
      peak oxygen uptake and MET (p = 0.013 and p = 0.024, respectively) and a
      prolonged respiratory exchange ratio (p = 0.022) in group 1 compared with group
      2. MET was significantly influenced by SOD level (p = 0.035). CONCLUSIONS: Lower
      antioxidative protection and impaired relaxation decrease cardiopulmonary
      capacity in hypertensive patients.

PMID- 17003544
TI  - QT interval dispersion as a new marker of restenosis after percutaneous
      transluminal coronary angioplasty.

PMID- 17003545
TI  - Predictors of in-hospital mortality present at admission among patients
      hospitalised because of decompensated heart failure.
AB  - Chronic heart failure (HF) is associated with a poor prognosis and causes
      considerable mortality. The aim of this study was to identify the admission
      characteristics useful to predict in-hospital mortality in patients admitted
      because of decompensation of HF. We evaluated 414 patients (age 76.2 years, 57%
      women). The hospital mortality rate was 11.1%. We identified 4 independent
      predictors of mortality: low Barthel index (odds ratio 1.03; 95% confidence
      interval 1.01-1.04), creatinine level >200 mumol/l (odds ratio 3.40; 95%
      confidence interval 1.51-7.66), peripheral oedema (odds ratio 3.12; 95%
      confidence interval 1.28-7.58) and the protective effect of the new onset of the
      disease (odds ratio 0.2; 95% confidence interval 0.08-0.77). In conclusion, the
      mortality of patients admitted to the hospital with an exacerbation of HF can be
      predicted if either poor functional capacity, renal insufficiency, peripheral
      oedema or previous diagnoses of HF are present. This clinical finding may help
      clinicians in their decision making in HF in the emergency room.

PMID- 17003546
TI  - Fetal head biometry assessed by fetal magnetic resonance imaging following in
      utero myelomeningocele repair.
AB  - OBJECTIVE: To examine the impact of fetal myelomeningocele (MMC) repair on fetal
      head biometry and cerebrospinal fluid (CSF) spaces assessed by magnetic resonance
      imaging (MR) studies. STUDY DESIGN: Axial measurements of intracranial structures
      were taken at defined anatomical landmarks. Pre- and postnatal head biometry data
      and CSF spaces obtained from in utero repaired MMC fetuses (n = 22) were compared
      to the pre- and postnatal measurements of MMC patients that underwent standard
      neurosurgical MMC repair after birth (n = 16) and a cohort of age-matched control
      patients (prenatal, n = 52; postnatal, n = 9). RESULTS: In fetuses with MMC,
      initial MR scans showed an almost complete absence of supratentorial and
      posterior fossa CSF spaces. No differences in postnatal CSF spaces were found
      between controls and prenatally repaired MMC newborns. In fetuses with postnatal
      MMC repair, CSF spaces remained significantly reduced (p < 0.0001). The mean
      ventricular diameter (VD) increase in the postnatal repaired MMC group was
      significantly higher compared to the mean percentage of VD increase in the fetal
      repaired MMC group (6.4 vs. 4.2 mm; p = 0.02). Pre- and postnatal brain thickness
      measurements were significantly reduced in both MMC populations compared to age
      matched normal values (p < 0.0001). In contrast to postnatally repaired patients,
      in utero repair fetuses showed significant reversal of hindbrain herniation and
      normalization of the posterior fossa CSF spaces. CONCLUSION: Mid-gestational
      repair of MMC promotes normalization of extra-axial CSF spaces. Due to
      progressive ventriculomegaly, brain thickness remains decreased in both prenatal
      repaired and age-matched non-repaired MMC patients when compared to age-matched
      normal values. Restoration of CSF volume in the posterior fossa after in utero
      repair is indicative of reversal of hindbrain herniation.

PMID- 17003547
TI  - A case of monochorionic twin pregnancy complicated with intrauterine single fetal
      death with successful treatment of intrauterine blood transfusion in the
      surviving fetus.
AB  - We report a case of monochorionic twin pregnancy complicated with single fetal
      demise that received successful treatment of intrauterine transfusion for severe
      anemia of the surviving fetus. A single fetal demise occurred at 20 weeks of
      gestation and middle cerebral artery peak systolic velocity (MCA-PSV), a marker
      for fetal anemia, showed marked elevation in the surviving fetus. Fetal blood
      sampling was immediately done and severe fetal anemia (hemoglobin = 5.5 g/dl,
      hematocrit = 16.8%) was confirmed, and then intrauterine transfusion was
      performed. After transfusion, MCA-PSV rapidly decreased to the normal value and
      remained within normal range until delivery. A healthy 2,640 g male infant was
      delivered at 35 weeks of gestation without anemic status and no neurological
      problem was found at 1-year old. The present report supports that intrauterine
      rescue transfusion is a useful treatment to prevent the adverse outcome of
      surviving fetus in monochorionic twin pregnancy complicated with single fetal
      demise, and monitoring of MCA-PSV is also useful to assess anemic status of the
      surviving fetus.

PMID- 17003548
TI  - Renal tubular dysgenesis: report of two cases in a non-consanguineous couple and
      review of the literature.
AB  - Renal tubular dysgenesis is a rare congenital abnormality of renal development
      characterized by short and poorly developed proximal convoluted tubules. It is
      associated to late-appearing oligohydramnios, Potter's sequence, pulmonary
      hypoplasia and calvarial bone hypoplasia with enlarged fontanels. The onset of
      oligohydramnios is delayed and variable, normally later than 22 weeks of
      gestation, conditioning variation in the expression of the other deformities. We
      report 2 cases of renal tubular dysgenesis occurring in a non-consanguineous
      couple.

PMID- 17003549
TI  - Premature rupture of membranes at 20 weeks: report of a successful outcome after
      transcervical application of fibrin glue.
AB  - A 30-year-old primigravida was admitted to hospital at 20 weeks of gestation
      because of premature rupture of membranes and oligohydramnios. The patient was
      maintained in bed rest and given intravenous ampicillin. Forty-eight hours later,
      after documenting the absence of infection and maintenance of the
      oligohydramnios, fibrin glue was applied transcervically under ultrasound
      control. There was subjective improvement in amniotic fluid volume after
      treatment, but always within the criteria of oligohydramnios. Fibrin glue
      application was repeated twice due to reported increase in fluid loss and
      diminished amniotic fluid volume on ultrasound. Amoxicillin per os was started at
      23 weeks, and clavulanic acid was added at 26 weeks due to the isolation of an
      Escherichia coli on cervical-vaginal cultures. No signs of infection ensued until
      34 weeks, when an axillary temperature of 39.5 degrees C was detected together
      with a non-reassuring cardiotocographic pattern, the latter leading to the
      performance of an urgent cesarean section. The newborn had an Apgar score of
      9/10/10, umbilical artery pH of 7.32, and no external deformities. He showed no
      signs of lung hypoplasia and required no oxygen supplementation. Oropharyngeal
      and blood cultures revealed an E. coli infection and antibiotic treatment was
      started. No further complications occurred and he was discharged home on the 8th
      day of life. At 12 months, the child reveals a normal development. The mother had
      a mild and short-lasting wound infection and was discharged on the 8th
      postoperative day.

PMID- 17003550
TI  - Beckwith-Wiedemann syndrome presenting with an elevated triple screen in the
      second trimester of pregnancy.
AB  - BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a distinct clinical syndrome
      with unique features, generally diagnosed postnatally. CASE: A 26-year-old
      patient, gravida 4, para 3-0-0-3, was noted to have an abnormal maternal serum
      screen. Amniocentesis with imaging studies were remarkable only for a two-vessel
      umbilical cord and prominent maternal ovaries. The patient developed HELLP
      syndrome at 28 weeks and delivered a viable female infant with distinct clinical
      features. The diagnosis of BWS was confirmed by hypermethylation of the H19 gene
      on chromosome 11p15.5. CONCLUSION: This case describes a novel presentation of
      BWS and underscores the diagnostic potential of routine prenatal screens.

PMID- 17003551
TI  - Bruck syndrome: second antenatal diagnosis.
AB  - Bruck syndrome is characterized by the association of arthrogryposis and
      osteogenesis imperfecta. It is a distinct autosomal recessive disorder associated
      with normal collagen I. The main features are osteoporosis, long bone bowing and
      scoliosis due to vertebral deformities and congenital joint contractures. We
      describe a French girl who was born with ankle and wrist contractures (second
      antenatal discovery).

PMID- 17003552
TI  - Reversed pulmonary artery flow in isolated noncompaction of the ventricular
      myocardium.
AB  - OBJECTIVE: To investigate the morphology and genetics of a fetus at 22 weeks.
      This fetus demonstrated progressive fetal hydrops and cardiomegaly with
      retrograde flow in the pulmonary artery and progressive myocardial deterioration
      and heart failure. METHODS: Postmortem examination, light and electron microscopy
      of the myocardium, karyotyping, fetal DNA analysis, screening for mutations in
      the G4.5 gene, alpha-dystrobrevin gene, FKBP 12 gene, Desmin, Syntrophin and
      Cypher/ZASP genes, which have been described as being associated with
      noncompaction ventricular myocardium, using single-strand DNA conformation
      polymorphism analysis and DNA sequencing. RESULTS: The morphological diagnosis
      was compatible with noncompaction ventricular myocardium or spongyforme myopathy.
      The karyotype was normal. Mutation analysis in exons and introns of all six genes
      did not show any known mutation. CONCLUSION: Noncompaction ventricular myocardium
      or spongyforme myopathy may be associated with mutations in genes which have
      previously not been thought to be associated with this phenotype. Alternatively,
      this disease could be the result of abnormal cardiac hemodynamics.

PMID- 17003553
TI  - Does the source of laser energy influence the coagulation of chorionic plate
      vessels? Comparison of Nd:YAG and diode laser on an ex vivo placental model.
AB  - OBJECTIVES: To compare the histological effects of diode and Neodymium-Yttrium
      Aluminium Garnet (Nd:YAG) laser coagulation of chorionic plate vessels. METHODS:
      In selected chorionic plate vessels in an ex vivo term placenta perfused with
      warm saline solution, diode (wavelength 940 nm) and Nd:YAG (wave length 1,064 nm)
      laser were used with an output of 30, 40, and 50 W, and 55 and 70 W respectively
      using preset energy and duration of impact. All vessels were examined
      histologically blindly to the procedures' characteristics. RESULTS: A total of 23
      vessels were coagulated. Similar histological lesions were observed using diode
      and Nd:YAG lasers. The lesions were compatible with an acceptable clinical effect
      at all power outputs tested. The results were not related to the diameter or type
      of vessels. Lesions of the endothelium and reduction of the vessel lumen were
      best achieved with a diode laser at 40 W. CONCLUSION: Nd:YAG and Diode laser
      induce significant and comparable changes in chorionic plate vessels compatible
      with an efficient coagulation process under the experimental condition used.

PMID- 17003554
TI  - Intrauterine intestinal obstruction due to fetal midgut volvulus: a report of two
      cases.
AB  - Fetal midgut volvulus is quite rare, and few surviving infants--particularly
      cases with meconium peritonitis--have been reported in the literature. We report
      two cases of intrauterine intestinal obstruction due to fetal midgut volvulus
      associated with intestinal malrotation. In both cases, the infant survived after
      cesarean section delivery and appropriate surgical intervention, and they both
      continue to be in good overall condition. We discuss the prenatal signs and
      outcome of in utero intestinal volvulus. Close prenatal follow-up and appropriate
      timing of delivery in cases where ultrasound examination shows signs of fetal
      intestinal obstruction, as well as optimal postnatal treatment, are essential to
      reduce the morbidity and mortality associated with fetal midgut volvulus.

PMID- 17003555
TI  - CFTR DeltaF508 mutation detection from dried blood samples in the first trimester
      of pregnancy: a possible routine prenatal screening strategy for cystic fibrosis?
AB  - OBJECTIVE: The implementation and evaluation of a proposed wide-scale prenatal
      screening strategy, based on DNA isolated from dried blood spots in the first
      trimester of pregnancy, for the early detection of pregnancies at risk for cystic
      fibrosis (CF). METHODS: The screening was performed in conjunction with routine
      biochemical marker screening for Down's syndrome risk in the first trimester of
      pregnancy. DNA was isolated from 1,233 dried blood spots and analyzed for the
      presence of the CF transmembrane regulator DeltaF508 mutation. Women carriers
      were offered and accepted the option for additional full testing of their
      partners in order to assess the risk for the fetus. RESULTS: All 1,233 samples
      were successfully analyzed, identifying 23 DeltaF508 carriers, corresponding to a
      DeltaF508 carrier rate of approximately 1/55 (1.8%). All partners of the women
      carriers were further tested without revealing any need for further prenatal
      testing in this group. CONCLUSIONS: This study reveals the relatively high
      frequency of the DeltaF508 CF mutation in the Greek population. More importantly,
      we demonstrate that the proposed prenatal screening strategy, based on the ease
      and cost-effectiveness of the analysis for the detection of a single common
      mutation, can be considered as a feasible and practical approach for wide-scale
      prenatal screening for CF, following the sequential model. It is applied early on
      in pregnancy, allowing for the timely management of families at risk for the
      corresponding genetic disorders. Finally, it can easily be extended to include
      screening for other common genetic disorders in specific population groups.

PMID- 17003556
TI  - First trimester Down's syndrome screening shows high detection rate for trisomy
      21, but poor performance in structural abnormalities--regional outcome results.
AB  - OBJECTIVE: To evaluate whether first trimester screening markers are altered in
      pregnancies affected both by other chromosomal defects than trisomy 21 and
      structural anomalies and whether it is possible to detect these pregnancies by
      combined ultrasound and biochemical screening test. METHODS: Altogether 4,776
      singleton pregnancies underwent first trimester screening. Of them, 3,101 women
      were screened using a combination of maternal serum free hCG, pregnancy
      associated plasma protein A and nuchal translucency and 1,361 women with first
      trimester biochemistry without ultrasound. Nuchal translucency screening was
      performed between the 11th and 13+6th gestational weeks, and biochemistry 1-2
      weeks earlier. RESULTS: Using a fixed cut-off rate of 1:250 for Down's syndrome,
      the detection rate of trisomies 21, 18 and 13 were 92, 67 and 0%, respectively.
      All open defects, 85% of cardiac defects and other minor defects were not
      detected in first trimester screening. Majority of these structural abnormalities
      occurred in women under 35 years of age. CONCLUSION: First trimester Down's
      syndrome screening is effective in trisomy screening, but its performance in
      structural abnormalities is low, when used as a part of routine clinical
      practice. We conclude that it is too early to drop second trimester screening
      ultrasound entirely from antenatal care programs if a high detection rate is to
      be achieved also in structural defects.

PMID- 17003558
TI  - Long-term outcome of infants with twin-to-twin transfusion syndrome.
AB  - OBJECTIVE: To clarify the long-term neurodevelopmental outcome of twin-to-twin
      transfusion syndrome (TTTS) survivors. METHODS: From January 1994 to December
      2003, 33 newborns with TTTS who were derived from 18 monochorionic twin
      gestations were enrolled for the study. The development and growth at 3 or 6
      years of age were compared between TTTS survivors and weight-matched singleton
      controls. RESULTS: The mortality in TTTS (8/33: 24%) was significantly higher
      than that of the controls (7/80: 9%). Of all 12 TTTS patients who were diagnosed
      before 25 weeks and born before 28 weeks of gestation, in 10 (83%) it led to
      neonatal or intrauterine death. The morbidity of cerebral palsy, epilepsy, and
      mental retardation did not differ between TTTS and control patients. The
      morbidity and severity of neurological deficits at school age were similar in
      both groups. No growth parameters at 3 or 6 years of age differed between TTTS
      and controls. CONCLUSIONS: Morbidity, growth and development of TTTS survivors
      attained comparable levels of weight-matched controls, despite the higher
      neonatal mortality. These results suggest that the early management of TTTS is
      critical for refining the total outcome of the affected twins.

PMID- 17003559
TI  - Amniotic band syndrome with limb amputation after exposure to mifepristone in
      early pregnancy.
AB  - To date, the number of cases reported after exposure to mifepristone alone in
      early pregnancy is limited. In 24 cases, only 1 observation of fetal malformation
      associated with mifepristone has previously been reported. We report a case of
      amniotic band syndrome with limb amputation after exposure to mifepristone in
      early pregnancy. This association raises the question of a possible causal
      relationship.

PMID- 17003557
TI  - Parvovirus B19 infection in pregnancy studied by maternal viral load and immune
      responses.
AB  - OBJECTIVES: Facilitate risk assessment of vital complications in fetuses of
      pregnancies affected by acute parvovirus B19 (B19V) infection. DESIGN: Study of
      the natural course of maternal B19V infection in four cases, from early pregnancy
      on. SETTING: University Medical Center in the Netherlands. POPULATION: Pregnant
      mothers attending obstetric services. METHODS: Serial measurements of the
      maternal and fetal or neonatal viral load and antibody responses. MAIN OUTCOME
      MEASURES: Maternal and fetal/neonatal serum B19V viral DNA load and specific IgM
      and IgG antibodies in maternal serum. RESULTS: Peak viral load levels occurred
      within 1 week after maternal infection and peak IgM levels were observed 1 week
      after the peak viral load levels. Approximation of IgG and IgM ratios usually
      took place 4 weeks after infection. Vertical transmission occurred 1-3 weeks
      after maternal infection, suggesting that fetal infection occurs during the
      maternal peak viral load. CONCLUSIONS: Maternal B19V DNA load levels and IgM
      responses are useful to estimate the risk of parvovirus B19-associated fetal
      complications. The maternal peak viral load directly precedes the onset of fetal
      infection and may be used to indicate the stage of intrauterine B19V infection.

PMID- 17003560
TI  - Detection of DeltaF508del using quantitative real-time PCR, comparison of the
      results obtained by fluorescent PCR.
AB  - OBJECTIVE: Cystic fibrosis (CF) is the most common autosomal recessive genetic
      disorder in the Caucasian population. The molecular diagnosis is difficult since
      there are about 1,000 mutations in the CF transmembrane regulator gene. The
      DeltaF508del is the cause of the CF in 64% of the cases in Hungary. Our aim was
      to compare two polymerase chain reaction (PCR)-based method for the detection of
      DeltaF508del. METHODS: One hundred and sixteen DNA samples isolated from
      different tissues (84 blood samples, 18 chorionic villus samples and 14 amniotic
      fluid samples) were involved in the study. Fluorescent PCR with DNA fragment
      analysis and quantitative real-time PCR with melting curve analysis were
      performed on the DNA samples for the detection of DeltaF508del. RESULTS: Sixty
      five healthy normal samples, 43 heterozygous samples, 6 DeltaF508del homozygous
      samples and 2 DeltaF508C homozygous samples were detected by using quantitative
      real-time PCR combined with melting curve analysis. The fluorescent PCR method
      did not detect the DeltaF508C mutation and these two samples were diagnosed as
      normal healthy ones. CONCLUSIONS: The quantitative real-time PCR with melting
      curve analysis is a reliable and fast method for the detection of DeltaF508del.
      The results are ready in 1 h following the DNA isolation. The applied primer
      probe set with melting curve analysis gives additional information for the
      presence of other mutations in the DeltaF508del region.

PMID- 17003562
TI  - Caution in the interpretation of 'mosaic' prenatal karyotypes.

PMID- 17003561
TI  - Prostaglandin E2 induction of labor for isolated oligohydramnios in women with
      unfavorable cervix at term.
AB  - OBJECTIVE: To evaluate the maternal and neonatal outcomes of pregnancies
      complicated with isolated oligohydramnios at term, managed by induction of labor.
      METHODS: We conducted a retrospective case-control study. 138 women with
      uncomplicated oligohydramnios at term [amniotic fluid index (AFI) < or =5 cm] and
      a low Bishop score (< or =6) underwent induction of labor with prostaglandin E2.
      These women were compared to 67 women who underwent induction of labor at 42
      weeks' gestation and 276 women at low-risk pregnancy and spontaneous onset of
      labor, matched for parity and race. RESULTS: Cesarean section (CS) rate was
      similar in the study and the post-date group (17.4 and 17.9%, respectively), but
      significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75
      6.68). No differences were found with other outcomes. CONCLUSION: Pregnancies
      with isolated oligohydramnios at term apparently are not at higher risk of
      perinatal complications, but induction of labor is associated with increased rate
      of CS.

PMID- 17003563
TI  - High-level functional capacity and 4-year mortality in an 80-year-old population.
AB  - BACKGROUND: Little is known about the relationship between high-level functional
      capacity and mortality in elderly people. OBJECTIVE: To evaluate the relationship
      between high-level functional capacity, such as intellectual activity and social
      role, and 4-year mortality in a population of 80-year-old community residents.
      METHODS: Participating in the study were 697 individuals (277 males and 420
      females) out of 1,282 80-year-old individuals residing in Fukuoka Prefecture,
      Japan. To measure high-level functional capacity, the daily activities of 656 of
      the 697 participants were examined through questionnaires, accompanied by
      physical and laboratory blood examinations. The 697 participants were followed up
      for 4 years after the baseline examination. For subjects who died during that
      period, the date and cause of death were recorded from resident registration
      cards and official death certificates. RESULTS: The relative risk for all-cause
      mortality decreased with an increase in intellectual activity or total functional
      capacity, whereas no association was found between total mortality and either the
      ability to perform instrumental self-maintenance or the ability to maintain a
      social role. Similarly, the relative mortality risk due to cardiovascular
      diseases decreased with an increase in intellectual activity or total functional
      capacity. Mortality due to pneumonia also decreased with an increase in
      intellectual activity. CONCLUSION: In a population of 80-year-old community
      residents, levels of intellectual activity and total functional capacity may be
      associated with all-cause, cardiovascular, and pneumonia mortality, and may be
      strong predictors of survival.

PMID- 17003564
TI  - SNP-based analysis of genetic substructure in the German population.
AB  - OBJECTIVE: To evaluate the relevance and necessity to account for the effects of
      population substructure on association studies under a case-control design in
      central Europe, we analysed three samples drawn from different geographic areas
      of Germany. Two of the three samples, POPGEN (n = 720) and SHIP (n = 709), are
      from north and north-east Germany, respectively, and one sample, KORA (n = 730),
      is from southern Germany. METHODS: Population genetic differentiation was
      measured by classical F-statistics for different marker sets, either consisting
      of genome-wide selected coding SNPs located in functional genes, or consisting of
      selectively neutral SNPs from 'genomic deserts'. Quantitative estimates of the
      degree of stratification were performed comparing the genomic control approach
      [Devlin B, Roeder K: Biometrics 1999;55:997-1004], structured association
      [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945-959] and
      sophisticated methods like random forests [Breiman L: Machine Learning 2001;45:5
      32]. RESULTS: F-statistics showed that there exists a low genetic differentiation
      between the samples along a north-south gradient within Germany
      (F(ST)(KORA/POPGEN): 1.7 . 10(-4); F(ST)(KORA/SHIP): 5.4 . 10(-4);
      F(ST)(POPGEN/SHIP): -1.3 . 10(-5)). CONCLUSION: Although the F(ST )-values are
      very small, indicating a minor degree of population structure, and are too low to
      be detectable from methods without using prior information of subpopulation
      membership, such as STRUCTURE [Pritchard JK, Stephens M, Donnelly P: Genetics
      2000;155:945-959], they may be a possible source for confounding due to
      population stratification.

PMID- 17003565
TI  - Human population genetic structure and diversity inferred from polymorphic
      L1(LINE-1) and Alu insertions.
AB  - BACKGROUND/AIMS: The L1 retrotransposable element family is the most successful
      self-replicating genomic parasite of the human genome. L1 elements drive
      replication of Alu elements, and both have had far-reaching impacts on the human
      genome. We use L1 and Alu insertion polymorphisms to analyze human population
      structure. METHODS: We genotyped 75 recent, polymorphic L1 insertions in 317
      individuals from 21 populations in sub-Saharan Africa, East Asia, Europe and the
      Indian subcontinent. This is the first sample of L1 loci large enough to support
      detailed population genetic inference. We analyzed these data in parallel with a
      set of 100 polymorphic Alu insertion loci previously genotyped in the same
      individuals. RESULTS AND CONCLUSION: The data sets yield congruent results that
      support the recent African origin model of human ancestry. A genetic clustering
      algorithm detects clusters of individuals corresponding to continental regions.
      The number of loci sampled is critical: with fewer than 50 typical loci,
      structure cannot be reliably discerned in these populations. The inclusion of
      geographically intermediate populations (from India) reduces the distinctness of
      clustering. Our results indicate that human genetic variation is neither
      perfectly correlated with geographic distance (purely clinal) nor independent of
      distance (purely clustered), but a combination of both: stepped clinal.

PMID- 17003566
TI  - Molecular mechanisms of neonatal hyperinsulinism.
AB  - Congenital hyperinsulinism (CHI), characterized by profound hypoglycaemia related
      to inappropriate insulin secretion, may be associated histologically with either
      diffuse insulin hypersecretion or focal adenomatous hyperplasia, which share a
      similar clinical presentation, but result from different molecular mechanisms.
      Whereas diffuse CHI is of autosomal recessive, or less frequently of autosomal
      dominant, inheritance, focal CHI is sporadic. The most common mechanism
      underlying CHI is dysfunction of the pancreatic ATP-sensitive potassium channel
      (K(+)(ATP)). The two subunits of the K(+)(ATP) channel are encoded by the
      sulfonylurea receptor gene (SUR1 or ABCC8) and the inward-rectifying potassium
      channel gene (KIR6.2 or KCNJ11), both located in the 11p15.1 region. Germ-line,
      paternally inherited, mutations of the SUR1 or KIR6.2 genes, together with
      somatic maternal haplo-insufficiency for 11p15.5, were shown to result in focal
      CHI. Diffuse CHI results from germ-line mutations in the SUR1 or KIR6.2 genes,
      but also from mutations in several other genes, namely glutamate dehydrogenase
      (with associated hyperammonaemia), glucokinase, short-chain L-3-hydroxyacyl-CoA
      dehydrogenase, and insulin receptor gene. Hyperinsulinaemic hypoglycaemia may be
      observed in several overlapping syndromes, such as Beckwith-Wiedemann syndrome
      (BWS), Perlman syndrome, and, more rarely, Sotos syndrome. Mosaic genome-wide
      paternal isodisomy has recently been reported in patients with clinical signs of
      BWS and CHI. The primary causes of CHI are genetically heterogeneous and have not
      yet been completely unveiled. However, secondary causes of hyperinsulinism have
      to be considered such as fatty acid oxidation deficiency, congenital disorders of
      glycosylation and factitious hypoglycaemia secondary to Munchausen by proxy
      syndrome.

PMID- 17003567
TI  - Antonin vancura and arterial hypertension. 50 years' evolution in the conception
      of pathogenesis and treatment of the disease.
AB  - A historical overview of the important contributions of Prof. Antonin Vancura
      from Charles University Medical Faculty, Prague, to the broader understanding of
      the pathogenesis, clinical course and classification of arterial hypertension is
      given in his pivotal publication and first Czech monography 'High Blood
      Pressure'. His unique clinical series of 1,096 hypertensive patients with their
      long-term follow-up after 5, 10 and 15 years made it possible to work out the
      classification of hypertension not only on the basis of blood pressure readings,
      but also according to target organ damage--a principle which is close to the 2003
      classification of the European Society of Hypertension/European Society of
      Cardiology (ESH/ESC). In agreement with today's conception, Vancura emphasized
      already in 1942 the importance of metabolic changes and albuminuria for prognosis
      of the disease. In spite of the technical, instrumental and laboratory
      limitations, it is possible to gain from Vancura's publication a modern
      interpretation of his results given by a long-term follow-up of this large group
      of patients. In many ways, Vancura outstripped his time and his concepts
      approached today's standings and so founded one of the important schools of
      hypertension in Czechoslovakia and Europe.

PMID- 17003568
TI  - Estimation of the ratio of renal artery stenosis with magnetic resonance
      angiography using parallel imaging technique in suspected renovascular
      hypertension.
AB  - BACKGROUND: Renovascular hypertension, which may lead to end-stage renal failure,
      necessitates prompt diagnosis and medication. Although various diagnostic tools
      exist for evaluation of renal arteries, magnetic resonance angiography (MRA),
      with the improvement of hardware and software systems, has become a very
      promising technique in screening patients with suspected renal hypertension. In
      this study, we aimed to assess renal artery stenosis on MRA in patients with
      suspected renovascular disease using a parallel imaging technique which allows
      faster scanning with higher resolution. METHODS: Eighty-four patients with
      hypertension underwent MRA and digital angiography. RESULTS: MRA detected renal
      artery stenosis with a sensitivity rate ranging from 69.3 to 100% and specificity
      rate ranging from 85.7 to 96%. CONCLUSION: Contrast-enhanced MRA of renal
      arteries is very effective in the demonstration of renal artery stenoses and
      assessment of stenosis ratio. Furthermore, parallel imaging technology has
      improved this procedure by reducing the scan time. Renal MRA, as a diagnostic
      tool, can accurately direct patients with renovascular disease to intravascular
      treatment.

PMID- 17003569
TI  - Blockade of renin-angiotensin system reduces QT dispersion and improves
      intracellular Ca/Mg status in hemodialysis patients.
AB  - BACKGROUND: Electrolyte impairments are common in hemodialysis (HD) patients.
      Consequently, QT dispersion (QTd) is prolonged, correlating with high
      intracellular magnesium. In patients with cardiac disorders, renin-angiotensin
      system (RAS) inhibition reduces QTd. AIM: To compare the effects of ACE
      inhibition or AT-1 blockade on QTd duration and intracellular magnesium
      (Mg)/calcium (Ca) in peripheral blood mononuclear cells (PBMC) from chronic HD
      patients. METHODS: 24 HD patients received cilazapril for 8 weeks and, following
      a 2-week withdrawal, were switched to valsartan for additional 8 weeks. QTd
      measurements and PBMC isolation were performed at the beginning and the end of
      each period. Total intracellular Ca and Mg were assessed by atomic spectrometer,
      and cytosolic free Ca2+ by fluorocytometer. RESULTS: Both treatments
      significantly decreased QTd, demonstrating similar reduction magnitudes. In both
      groups, PBMC exhibited basally low cytosolic Ca2+ and undisturbed high
      transmembrane Ca2+ influx following phytohemagglutinin stimulation. Total
      intracellular Ca was increased, while Mg was reduced, following either treatment.
      The total intracellular Ca/Mg ratio inversely correlated with QTd duration.
      CONCLUSIONS: (1) RAS inhibition reduces prolonged QTd in HD patients. (2) In PBMC
      from ordinarily Ca-depleted HD patients, RAS suppression brings about elevation
      of total intracellular Ca. (3) RAS blockade decreases high intracellular Mg in
      PBMC from HD patients. Consequently, the Ca/Mg ratio increases, inversely
      correlating with QTd reduction.

PMID- 17003570
TI  - Prevalence and risk factors of atherosclerotic renal artery stenosis in 1,200
      chinese patients undergoing coronary angiography.
AB  - AIMS: Atherosclerotic renal artery stenosis (ARAS) is a common and potentially
      reversible cause of end-stage renal failure. Our study aimed to determine the
      prevalence and predictors of ARAS in Chinese patients undergoing coronary
      angiography for suspected coronary heart disease (CAD), or for acute or chronic
      myocardial infarction. METHODS: Selective renal arteriography was performed
      immediately after coronary angiography in 1,200 consecutive patients. Medical
      history and laboratory data were obtained before the procedure. Significant renal
      artery stenosis was defined as > or =50% narrowing of the luminal diameter. Uni-
      and multivariate logistic regression analyses were made to explore the
      association of the clinical and laboratory variables, including some items which
      had never or rarely been studied, with ARAS or CAD. RESULTS: Of the 1,200
      patients, 840 were male and 360 female. Their mean age was 62 +/- 10 years. Low
      grade (<50%) and significant coronary artery stenosis was found in 108 (9%) and
      610 (51%) patients respectively. By multivariate logistic regression analysis,
      risk factors associated with the presence of coronary artery stenosis included
      male, older age, smoking, high serum concentration of low density lipoprotein,
      lipoprotein (a), and fast blood glucose > or =7.0 mmol/l. Significant ARAS was
      present in 116 (9.7%) patients, of which 20 (1.7%) were bilateral. The incidence
      of ARAS was similar in patients with suspected CAD or myocardial infarction.
      Multivariate logistic regression analysis showed the association of the clinical
      variables with ARAS included: older age, hypercholesterolemia, a more than 10
      year history of hypertension, proteinuria and S(Cr) > or =133 micromol/l. The
      severity of ARAS is significantly related to the severity of coronary artery
      disease. CONCLUSION: ARAS is a frequent finding in Chinese patients undergoing
      coronary angiography, especially in patients with significant coronary artery
      stenosis and risk factors for ARAS. Renal arteriography can be a helpful
      examination in these patients.

PMID- 17003571
TI  - Regulation of ROMK (Kir 1.1) channel expression in kidney thick ascending limb by
      hypertonicity: role of TonEBP and MAPK pathways.
AB  - The present study assessed the mechanisms by which hypertonicity caused by NaCl
      enhances the renal outer medullary potassium channel (ROMK) mRNA abundance in rat
      kidney medullary thick ascending limb (MTAL) and in cultured mouse TAL cells.
      Using the run-off technique, we observed that the ROMK gene transcription rate in
      nuclei isolated from MTAL fragments was enhanced approximately 40% by a high NaCl
      medium. In MTAL fragments, hypertonicity (450 mosm) caused by NaCl, not by
      mannitol or urea, enhanced both ROMK mRNA abundance and tonicity-responsive
      enhancer binding protein (TonEBP) total abundance and nuclear localization. In an
      immortalized mouse TAL cell culture in which ROMK is apically expressed,
      hypertonicity caused by both NaCl and mannitol, not urea, enhanced both ROMK mRNA
      abundance and TonEBP total abundance and nuclear localization. Confocal
      microscopy confirmed an increased nuclear translocation of TonEBP in response to
      NaCl-induced hypertonicity. Finally, inhibition of the p38 MAPK pathway by
      SB203580 and of the ERK pathway by PD98059 abolished the NaCl-induced stimulation
      of TonEBP and ROMK. These results establish that mRNA expression of ROMK is
      augmented in the MTAL by NaCl-induced hypertonicity through stimulation of ROMK
      gene transcription, and that TonEBP and the p38 MAPK and ERK pathways are
      involved in this effect.

PMID- 17003572
TI  - Angiotensin II regulates extraneuronal dopamine uptake in the kidney.
AB  - BACKGROUND/AIMS: Angiotensin II (ANG II) and dopamine (DA) are both important
      regulators of sodium and water transport across renal proximal tubules. Previous
      studies demonstrate that atrial natriuretic factor (ANF) can regulate renal DA
      uptake and thereby Na(+),K(+)-ATPase activity in the external renal cortex. As
      ANG II counteracts most of the ANF biological effects, the aim of the present
      study was to evaluate ANG II effects on renal DA metabolism and identify the
      receptor involved. METHODS: To determine ANG II effects on renal DA metabolism,
      we evaluated (3)H-DA uptake in vitro in kidney tissue samples from Sprague-Dawley
      rats. RESULTS: The results indicate that ANG II decreased DA uptake at 30 min, in
      a concentration-response fashion, in the external and juxtamedullar cortex. DA
      uptake was characterized as an extraneuronal uptake and decreased at 0 degrees C
      and in sodium-free medium. The biological receptor type involved was AT(1), since
      losartan reversed ANG II effects on DA uptake while AT(2) receptors were not
      involved since PD 123319 did not affect ANG II effects. The absence of sodium did
      not alter the ANG II response. CONCLUSION: ANG II inhibits DA uptake by kidney
      tubular cells. These effects implicate AT(1) receptors without participation of
      AT(2) receptors. This mechanism could be related to the DA effects on sodium
      reabsorption and linked to ANG II antinatriuretic effects in the kidney.

PMID- 17003573
TI  - Additive effect of dextromethorphan on the inhibitory effect of anti-NT4 on
      morphine tolerance.
AB  - It has been proposed that opioid tolerance is a model of neuronal plasticity
      similar to learning and memory. Recent evidence suggests that neurotrophins may
      be involved in synaptic development and plasticity. Observations indicate that
      neurotrophin 4 (NT4) is required for the synaptic plasticity mediating both
      tolerance and memory. Also there are lines of evidence to indicate that NMDA
      receptors are involved in the neural plasticity underlying the development of
      opiate tolerance. Neurotrophins affect central transmission postsynaptically by
      enhancing NMDA receptor responsiveness. So we used the clinically available NMDA
      receptor antagonist, dextromethorphan, and the neurotrophin 4 antibody, anti-NT4,
      concomitantly and alone to investigate their effects on morphine tolerance.
      Tolerance was induced by injecting morphine (7 and 10 mg/kg i.p.) once per day
      for 4 days. Anti-NT4 (1 microg/rat i.c.v.) was administered 15 min before
      morphine. Results showed that chronic concomitant treatment of anti-NT4 with
      morphine in both doses inhibited the development of morphine tolerance. Also
      acute treatment of anti-NT4 significantly reversed the tolerance that was induced
      by morphine 7 mg/kg but failed to reverse the tolerance of morphine 10 mg/kg.
      Dextromethorphan in both doses (10 or 30 mg/kg) has an additive effect on the
      inhibitory effect of anti-NT4 on the reversal of morphine tolerance (7 mg/kg).
      These findings provide additional support for the hypothesis that NMDA receptor
      and NT4 may be involved in neural plasticity underlying opiate tolerance.

PMID- 17003574
TI  - Anatomy and physiology of neurological compensatory mechanisms.
AB  - The skull is a unique part of anatomy. It exists in a state of dynamic
      equilibrium. The components of the skull and their role in maintaining integrity
      and normal intracranial pressure will be reviewed in this article. Compensatory
      mechanisms that attempt to prevent the destructive effects of cerebral ischemia
      and injury will be discussed.

PMID- 17003577
TI  - Prevention of ventilator-associated pneumonia: what nurses can do.
AB  - Ventilator-associated pneumonia is the second most common hospital-acquired
      infection in medical intensive care units in the United States. Prevention of
      ventilator-associated pneumonia must be regarded as one of the most important
      issues in critical care and it has already become one of the core intensive care
      unit performance measures proposed by the Intensive Care Advisory Panel of the
      Joint Commission on Accreditation of Healthcare Organizations. This article
      focuses on prevention strategies which can be applied by critical care nurses
      during daily care.

PMID- 17003578
TI  - Coronary artery disease in women: the myth still exists.
AB  - There is a large media effort currently available to increase awareness of
      coronary artery disease in women. Despite this, there is still a misconception
      among some people, and unfortunately, some healthcare providers, that heart
      disease is a man's disease. This article will review some of the information
      about women and coronary artery disease; a short review of the literature,
      symptoms, diagnostic tests, and treatment pertinent to women; and the action
      nurses can take to help educate the public, and other healthcare providers, about
      this deadly threat.

PMID- 17003580
TI  - Separating medical and ethical: helping families determine the best interests of
      loved ones.
AB  - Critical care nurses are often confronted with situations where the wishes of an
      incompetent patient on life support are undocumented and the family is struggling
      with the decision to either continue or withdraw life support. It is important
      that critical care nurses are able to identify their values in this and similar
      situations. With a better understanding of personal values, nurses are better
      able to provide medical information families need to make decisions about life
      support, without their ethical opinions being confused with medical knowledge.
      This article presents a framework using 2 values that are essential to decisions
      about life support, the sanctity of life, and quality of life to assist critical
      care nurses to identify values.

PMID- 17003581
TI  - Root cause analysis and nursing management responsibilities in wrong-site
      surgery.
AB  - The most fundamental reason for the failure or inefficiency of a process, in any
      work setting, is referred to as a root cause. Root cause analysis is the process
      of learning from consequences wherein healthcare providers take a step back and
      gain knowledge from near-misses, adverse events, or sentinel events in the
      operating room and all areas of healthcare. This article discusses root cause
      analysis and nursing management responsibilities as they relate to wrong-site
      surgery.

PMID- 17003584
TI  - A retrospective pilot study: management of patients with heart failure.
AB  - An epidemic disease - a major cause of chronic disability - congestive heart
      failure adversely affects the health of millions. Congestive heart failure is the
      most frequent cause of cardiovascular hospital admissions and shares a
      significant responsibility for the high cost of healthcare. Despite medical and
      technological advances, studies show that the treatment of heart failure is
      suboptimal. Physician knowledge and awareness of appropriate treatment may
      contribute to patient compliance and improve delivery of healthcare. The purpose
      of this article is to examine how patients with heart failure in a heart failure
      clinic are managed. Recommendations are proposed and the role of nurses and
      clinicians in heart failure management is discussed.

PMID- 17003585
TI  - Intensive care research coordinators: who are they and what do they do? Results
      of a binational survey.
AB  - Research coordinators in intensive care are a growing specialty about which
      little is known. This cross-sectional study surveyed the Australia and New
      Zealand Intensive Care Research Coordinators' Group (n = 49) regarding
      demographics, education, employment history, job structure, and role content.
      Most research coordinators were highly qualified and experienced nurses who
      undertake pharmaceutical trials, multicenter projects, departmental medical and
      nursing research, audits and data registries, and their own projects.

PMID- 17003590
TI  - Answering without an answer.

PMID- 17003592
TI  - Homocysteine--should we screen and treat in preventive cardiology programs?

PMID- 17003593
TI  - Dietary measures and exercise training contribute to improvement of endothelial
      function and atherosclerosis even in patients given intensive pharmacologic
      therapy.
AB  - PURPOSE: Atherosclerosis contributes to cardiovascular mortality and morbidity
      even with aggressive lipid management. Our objective is to determine whether a
      combined pharmacological and lifestyle intervention can improve atherosclerosis.
      METHODS: We conducted a 2-year observational study at a specialized clinic in a
      tertiary care hospital. One hundred fifty-six subjects with coronary disease were
      enrolled in an intensive pharmacological management and lifestyle measures
      (including counseling and exercise training) program designed to reach specific
      targets. The main outcome measures were carotid intima media thickness and plaque
      area; brachial artery flow-mediated dilation; nitroglycerin-mediated dilation;
      flow-mediated dilation-nitroglycerin-mediated dilation ratio; laboratory
      parameters including lipids, glucose, creatinine, and homocysteine; and physical
      fitness. RESULTS: At completion, there were improvements in lipids and physical
      fitness. There were no overall changes in flow-mediated dilation, nitroglycerin
      mediated dilation, or carotid intima media thickness in the entire cohort.
      However, multivariate logistic regression showed that dietary and exercise
      variables, such as increasing fiber intake and reducing body weight and body fat
      percentage, were independent predictors of improvements in endothelial function
      and carotid plaque burden. CONCLUSIONS: Even in the setting of intensive
      pharmacological therapy, lifestyle interventions, including exercise training and
      dietary changes, are important determinants of improved endothelial function and
      atherosclerosis.

PMID- 17003594
TI  - Diet and exercise: are they worth it in the era of advanced pharmacotherapy?

PMID- 17003595
TI  - A comparison of treadmill and arm-leg ergometry exercise testing for assessing
      exercise capacity in patients with peripheral arterial disease.
AB  - PURPOSE: To compare the results of treadmill exercise testing (TM) to arm-leg
      ergometry testing (AL) in patients with peripheral arterial disease (PAD).
      METHODS: Twelve men and 8 women with PAD (mean age, 62 +/- 10 years) completed a
      treadmill test and an arm-leg ergometer exercise test. Oxygen uptake, heart rate,
      rate-pressure product (x10(-3)), ratings of claudication and perceived exertion,
      and power were measured. RESULTS: Peak oxygen uptake, heart rate, and rate
      pressure product were similar between TM and AL. Exercise duration was longer and
      the peak power higher on the AL than on the TM. Claudication pain > or =3/4 was
      the reason for test termination in all subjects during TM test and in 13 subjects
      during AL. Nine patients discontinued due to severe claudication on both tests,
      but the pain occurred later in AL than TM. CONCLUSIONS: Although peak oxygen
      uptake was similar between the 2 exercise tests, patients with PAD exercised
      longer and to a higher peak power during the AL. These data suggest that the AL
      test may be used to evaluate peak exercise capacity in patients with PAD. The AL
      may also provide an alternate method for detecting PAD and coronary heart
      disease.

PMID- 17003596
TI  - A novel method of exercise stress testing in patients with peripheral arterial
      disease.

PMID- 17003597
TI  - Development and validation of the Tangible, Informational, and Emotional Social
      Support Survey.
AB  - BACKGROUND: Social support is an important resource for chronic disease
      management. However, it is not routinely assessed in the context of caring for
      patients with cardiovascular disease or as part of the cardiovascular
      rehabilitation process. The objective was to develop a survey designed to measure
      the types of social support that are necessary in cardiovascular disease
      prevention and management. METHODS: Items were derived based on qualitative
      interviews with 63 patients regarding their perception of the most helpful types
      of social support in health behavior modification. Test-retest reliability was
      determined among 43 new patients. Factor analysis was conducted to determine the
      structural domains of the survey. The survey was then validated against the
      Medical Outcomes Study Social Support Survey in 130 patients. RESULTS: The survey
      used, which was called Tangible, Informational, and Emotional Social Support
      Survey, contains 16 items that explore tangible, informational, and emotional
      social support. Cronbach coefficient was .80. Exploratory factor analysis
      revealed a 4-factor solution, which accounted for 54% of the total variance.
      Patients who were married had higher scores (P < .05), compared with those who
      were not and scores on Tangible, Informational, and Emotional Social Support
      Survey correlated with the scores on the Medical Outcomes Study Social Support
      Survey (r = 0.82). CONCLUSIONS: Tangible, Informational, and Emotional Social
      Support Survey is a patient-derived, reliable, and valid social support survey.
      It can be used to capture salient aspects of social support that may facilitate
      health behavior modification in cardiovascular disease patients.

PMID- 17003598
TI  - Exercise-induced atrioventricular block: a report of 2 cases and review of the
      literature.

PMID- 17003599
TI  - Exertional hypotension: the possible role of cardiovascular autonomic neuropathy.

PMID- 17003600
TI  - The relationship between C-reactive protein and other cardiovascular risk factors
      in men and women.
AB  - INTRODUCTION: C-reactive protein (CRP) has emerged as an important indicator of
      risk for cardiovascular disease. The impact of gender on the relationship between
      CRP and other cardiovascular risk factors, however, has not been thoroughly
      investigated. METHODS: Ninety men and 75 women participated in this study. Age,
      resting systolic and diastolic blood pressure, resting heart rate, body mass
      index, total cholesterol, high-density lipoprotein, low-density lipoprotein,
      triglycerides, and hs-CRP were ascertained. Maximal oxygen consumption was
      obtained via treadmill testing, and aortic stiffness was measured using magnetic
      resonance imaging. RESULTS: Log hs-CRP level was significantly higher in the
      female subjects compared with the males subjects (0.86 +/- 0.67 mg/L vs 0.63 +/-
      0.44 mg/L, respectively; P = .003). In the male group, Pearson product moment
      correlation analysis showed that log hs-CRP was not significantly correlated (P >
      .10) with any of the other variables of interest. In the female group, however,
      log hs-CRP was significantly correlated (P < .05) with total cholesterol (r =
      0.30), low-density lipoprotein (r = 0.27), tryglycerides (r = 0.51), and body
      mass index (r = 0.36). Linear regression analysis determined that triglycerides
      and body mass index explained 30% of the variability in log hs-CRP. CONCLUSIONS:
      These results indicate that the relationship between CRP and other cardiac risk
      factors is different between apparently healthy men and women. The prognostic
      characteristics of CRP and the impact of statin therapy on CRP may therefore
      differ between men and women. Future research should be directed toward resolving
      this issue.

PMID- 17003602
TI  - The effect of single set resistance training on strength and functional fitness
      in pulmonary rehabilitation patients.
AB  - PURPOSE: The primary goal of pulmonary rehabilitation (PR) is for patients to
      achieve and maintain their maximum level of independence and functioning in the
      community. Traditional PR uses a predominantly aerobic/endurance approach to
      rehabilitation with little or no inclusion of exercises to increase strength. Few
      studies have investigated the impact of resistance training on PR despite growing
      evidence supporting its efficacy to improve physical function (functional
      fitness) in both healthy individuals and those with chronic disease. The purpose
      of this study was to investigate the effect of single-set resistance training on
      strength and functional fitness outcomes in PR patients. METHODS: Twenty PR
      patients, 60 to 81 years old, were randomly assigned to an 8-week endurance-based
      PR program (ET) or an ET plus resistance training program (RT). RESULTS: Strength
      increased in RT (P < .05) and decreased in ET for both upper and lower body.
      Functional fitness improved (P < .05) in 5 of 7 tests for RT compared with 2
      tests for ET. CONCLUSIONS: Single set RT can elicit significant improvements in
      both strength and functional fitness, which is not obtained by traditional PR
      alone. Our results are comparable to other studies with similar outcomes using
      multiple-set RT protocols. These findings may have important implications for
      program design, application, and adherence in PR.

PMID- 17003604
TI  - News on performance, efficiency and quality of care indicators.

PMID- 17003603
TI  - Getting serious about strength training.

PMID- 17003605
TI  - A one-year review of craniofacial injuries in amateur soccer players.
AB  - The purpose of this study was to investigate the rate of craniofacial injuries in
      amateur soccer and help us better understand the nature of these injuries.
      Retrospective study was carried out using records from the patients with
      craniofacial injuries associated with soccer activities. All data were collected
      on the basis of sex, age, type and anatomic site of the injury. In the one-year
      period of this study, 11/53 cases with craniofacial injuries associated with
      soccer activities have been treated in our clinic. The highest incidence was in
      the 18 to 24 year age group (mean age 20.7) with male propensity. The majority of
      the patients suffered from dento-alveolar fractures (36%), followed by
      temporomandibular joint disorders (27%), mandibular fractures (27%), and nasal
      fractures (9%). The most common cause of the fractures was impact against another
      player (63.6%), followed by impact against equipment (18.2%) and impact against
      the ground (18.2%). These results show that there is a high risk of potential
      oral and craniofacial injury during soccer activities.

PMID- 17003606
TI  - Denervation of the painful temporomandibular joint.
AB  - The successful management of temporomandibular joint (TMJ) pain remains elusive.
      Often the initial relief of pain is complicated by recurrence of the symptoms.
      This time frame suggests that the pain may be related to neuromas of the nerves
      that innervate the TMJ. In 2003, an anatomic description of the innervation of
      the TMJ suggested that denervation of this joint might be the appropriate
      treatment for pain resistant to traditional forms of therapy. In January, 2005,
      this approach was used to treat recalcitrant left TMJ pain in a 21-year-old woman
      with congenital hearing loss who had recurrent dislocations of her TMJ articular
      disc. She previously had two arthroscopic surgeries and one open attempt to treat
      her TMJ pain. The last failed TMJ surgery created a painful neuroma that
      prevented her from wearing her hearing aid. A medial and lateral denervation of
      the TMJ joint was done. The successful results of this surgery are presented at
      one-year follow-up. The technical considerations of this approach and risk to the
      facial nerve are discussed.

PMID- 17003607
TI  - Moustache reconstruction in patients with cleft lip: (final aesthetic touches in
      clefts-part ii).
AB  - Men with clefts often have limited or even missing moustache growth in scar areas
      or in the upper lip prolabium. However the histological testing showed the
      absence or at least the inactive form of androgenic receptor in hair follicle of
      cleft site, transplantation of autologous grafts harvested from hair was
      successful in all six cases either into scars or the prolabium. A more natural
      effect was achieved by using micrografts. The positive reaction of patients
      proved there is a need for detailed treatment in highly outgoing individuals.

PMID- 17003608
TI  - Computer-assisted surgical treatment of orbitozygomatic fractures.
AB  - Orbitozygomatic fractures pertain to the most common injuries in craniofacial
      trauma patients. Accurate fracture reduction is of high importance for a
      successful outcome. This pilot study was performed to assess the potential
      benefit of surgical navigation to aid in orbitozygomatic fracture reduction. A
      non-comparative series of five consecutive patients with severely displaced
      orbitozygomatic fractures was treated using the guidance of computed tomography
      (CT)-based surgical navigation. Using a previously developed software platform,
      the fracture was reduced virtually by a three-dimensional shifting of the
      orbitozygomatic complex within the patient's preoperative multimodal CT data set.
      This treatment plan was transferred to a navigation system. Fracture reduction
      was performed according to the treatment plan using surgical navigation.
      Intraoperative control of fracture reduction by comparing the real with the
      virtual bone position using surgical navigation showed up as a helpful tool.
      Accurate treatment planning and immediate evaluation of craniofacial surgery
      outcome are the benefits of the new approach demonstrated. A major drawback of
      the presented approach is a high consumption of human and financial resources. A
      larger clinical series with long-term follow-up will be needed to determine
      reproducibility and cost-effectiveness. In addition to bone repositioning, a
      future application may include simulation of craniofacial osteotomies.

PMID- 17003609
TI  - Frontal lobe atrophy after prolonged frontal bone defect.
AB  - After a frontofacial monobloc in a 12-year-old Crouzon patient, the frontal bone
      was lost to infection. The patient did not attend postoperative appointments and
      was lost to follow-up. Nine years later, he reappeared requesting surgical
      reconstruction. This was performed satisfactorily with a titanium plate; however,
      it became apparent later that he had considerable atrophy of the frontal lobes
      and had developed the unstable behavior of patients who have undergone a frontal
      lobotomy. The atrophy would appear to be the consequence of the long-term absence
      of the frontal bones and the resultant repetitive frontal lobe microtrauma.
      Frontal infection and subsequent loss of the frontal bone is a recognized
      complication of monobloc advancement for faciocraniosynostosis and is mainly
      caused by the communication between the oronasal cavities and the cranial base.
      The frontal bone defect would normally be repaired after a delay of 6 months to a
      year with no significant sequelae. We present the unusual case of a patient whose
      frontal defect was not reconstructed for 9 years and who, as a result, developed
      frontal lobe atrophy and subsequent severe psychologic and behavioral
      difficulties.

PMID- 17003610
TI  - Orbital reconstruction: bone-anchored implants.
AB  - The authors present their experience on reconstruction by extraoral bone-anchored
      implants technique, showing two patients from a total of 13, treated for orbital
      reconstruction. They were selected from 66 patients treated for reconstruction of
      orbit, ear and nose using this technique by the staff of the Department of
      Plastic and Reconstructive Surgery of the University of Tor Vergata, Rome, Italy.
      They underwent orbital emptying due to cancer pathology. Surgical technique is
      described in detail; its final purpose being positioning of titanium fixtures on
      the orbital borders, necessary to anchor the silicone epithesis. The advantages
      and potential limits of this technique are exposed, exposing the important role
      of patient's compliance. The importance of preliminary study on the patients is
      also emphasized and includes clinical evaluation and instrumental examination for
      surgical planning, completed by a photographic study in the three standard
      projections.Satisfactory aesthetic results were obtained by the use of this
      technique and the authors believe it may represent a valid option; complementary
      to more traditional ones, but is a first choice in patients who cannot endure
      major surgery or in case of failure of traditional techniques.

PMID- 17003611
TI  - Scar flap for extension of the nasal and lip soft tissue shell in secondary cleft
      deformities: final aesthetic touches in clefts-part iii.
AB  - A scar flap is formed with the pedicle at the lateral part of the columella base
      at the cleft side, that is, in the center of the affected region. It enables flap
      placement according to individual need. A prospective evaluation was performed in
      a group of 76 patients with cleft lip and palate, all operated on by the same
      plastic surgeon. The flap was used to improve the height of the columella and the
      extent of nasal mucosa on the frontal septum and on the nostril base in the
      vestibule. In the lip, the flap raised its height and improved proportionality.
      The average area of flap used in a unilateral deformity was 42 mm. Both flaps in
      a bilateral deformity were 77 mm. The average follow-up was 22.4 months. Neither
      local nor general complications were noted apart from a recurrence of the
      deformity of the nasal septum in 7.9% of patients. The nasal passage was improved
      in 59.9% of patients and normalized in 19.6% upon follow-up rhinomanometry, but
      nevertheless, only one third of patients overcame their dynamic stereotype of
      breathing by the mouth. Anthropometric measurements showed an absence of
      statistically significant differences between patients after surgery and healthy
      individuals in crucial parameters (nasal tip projection, length of columella,
      nasolabial angle, nasal angle, and lip angle). The loss of the stigmatizing
      deformity is based on rotation of the nasolabial angle in relation to the
      aesthetic axis of the face. Direct examination proved aesthetic and functional
      improvement as statistically significant in 92.1% of patients.

PMID- 17003612
TI  - Arterial features of inner canthus region: confirming the safety for the flap
      design.
AB  - The medial canthus represents a fixed-point fulcrum that is necessary for eyelid
      function. The aim of the study was to investigate the arterial distribution of
      the inner canthus. The origin, calibration, and branches of the inner canthus
      arteries and their topographical relations were examined by dissecting 19
      cadavers, injecting red latex to their corresponding 38 nasal sections before the
      dissection. The distance from the dorsal nasal artery to the inner canthus was
      found to be 7.2 +/- 0.3 mm. In this study, the average diameter of the dorsal
      nasal artery was 0.74 mm on the right side and 0.88 mm on the left. Concerning
      the course of dorsal nasal artery on the lateral side of the nose, 4 types were
      observed. In most of the examples (44.7%), dorsal nasal artery anastomosed with
      angular artery via thick branch and gave off supplying branches to the medial
      canthus and to the lateral side of the nose. Dorsal nasal artery is a vessel of
      satisfactory size and is potentially a good vascular source for a thin free flap.
      It may be an ideal flap to reconstruct the eyelid defect for texture and color
      similarity of the inner canthus skin. A better understanding of the inner canthus
      vascularity should allow modification of reconstructive techniques and reduce
      postoperative complications.

PMID- 17003613
TI  - Stereolithography for craniofacial surgery.
AB  - Advances in computer technology have aided in the diagnostic and clinical
      management of complex congenital craniofacial deformities. The use of
      stereolithographic models has begun to replace traditional milled models in the
      treatment of craniofacial deformities. Research has shown that stereolithography
      models are highly accurate and provide added information in treatment planning
      for the correction of craniofacial deformities. These include the added
      visualization of the complex craniofacial anatomy and preoperative surgical
      planning with a highly accurate three-dimensional model. While the
      stereolithographic process has had a beneficial impact on the field of
      craniofacial surgery, the added cost of the procedure continues to be a hindrance
      to its widespread acceptance in clinical practice. With improved technology and
      accessibility the utilization of stereolithography in craniofacial surgery is
      expected to increase. This review will highlight the development and current
      usage of stereolithography in craniofacial surgery and provide illustration of it
      use.

PMID- 17003614
TI  - Association between osteonecrosis of the jaws and chronic high-dosage intravenous
      bisphosphonates therapy.
AB  - Bisphosphonates (BPs) are used to inhibit bone resorption. Recently, they have
      been used in cancer patients to prevent bone loss due to bone metastasis.
      Fourteen consecutive patients, undergoing BPs monthly IV infusion due to
      neoplastic bone diseases, were diagnosed with osteonecrosis of the jaws. None of
      the patients had been previously undergoing radiotherapy of the head and neck
      region. Eight patients showed maxillary involvement, and nine patients had had a
      recent tooth extraction in the osteonecrosis areas. Biopsies and surgical
      debridment were performed. Histologically, none of the patients showed signs of
      bone metastasis. As high-dosage long-term BP therapy appears to be associated
      with osteonecrosis of the jaws, dental practitioners should exercise caution in
      the treatment of such patients.

PMID- 17003615
TI  - Respiratory outcome of mid-face advancement with distraction: a comparison
      between Le Fort III and frontofacial monobloc.
AB  - Upper airway stenosis in patients with faciocraniosynostosis is very common and
      often severe. Mid-face advancement, either with a Le Fort III or concomitantly to
      a monobloc frontofacial advancement, may prevent a tracheotomy or result in its
      ablation. The amelioration of respiratory function appears to be much better if
      the mid-face advancement is combined with distraction osteogenesis, although
      large studies with long-term follow-up are rare. In this study we reviewed the
      respiratory outcome between Le Fort III with distraction and monobloc advancement
      with distraction in 55 faciocraniosynostotic patients. Early respiratory results
      of both procedures were very good and stable at long-term follow-up. The choice
      between a Le Fort III and a monobloc procedure is made based on presenting
      morphology, previous surgery, and age. Both can be expected to give a long
      lasting improvement of upper airway obstruction.

PMID- 17003616
TI  - Multiplanar distraction osteogenesis of fibula free flaps used for secondary
      reconstruction of traumatic maxillary defects.
AB  - Traumatic maxillary bone loss, if not treated acutely, is accompanied by
      contracture of the overlying soft tissue envelope and loss of facial projection
      in three dimensions. Reconstruction aimed at replacing the bony architecture,
      expanding the soft tissue envelope and establishing a platform for dental
      rehabilitation can be accomplished in a staged approach. We present two patients
      who underwent replacement of missing maxillary segments with a free fibula flap,
      followed by distraction of the free fibula in three dimensions and eventual
      dental rehabilitation with osseo-integrated implants.

PMID- 17003617
TI  - Experience with cranial implant-based prosthetic reconstruction.
AB  - Reconstruction of acquired or congenitally absent facial structures is a
      challenging task for the reconstructive surgeon. Often inadequate soft tissue,
      cartilaginous, or osseous support exists for a reconstruction which is
      functional, aesthetic, and achieved with a reasonable effort on the part of the
      surgeon and patient. Prosthetic reconstruction of these structures utilizing
      cranial implants is a viable option which offers several advantages when compared
      to traditional reconstructive techniques. We present our experience with 114
      cranial implants in 32 patients for craniofacial reconstruction. One hundred
      fourteen cranial implants were placed in a total of 32 patients for
      reconstruction of facial structures. Indications for cranial implants with
      prosthetic reconstruction were lack of adequate tissue for reconstruction, failed
      reconstructive attempts, and selection of the technique by the patient. Seventy
      two implants were placed in the mastoid region, 31 within the orbit, 7 within the
      nasal cavity, with four additional implants for the reconstruction of eyebrows.
      Cranial implants were followed by clinical and radiographic examination at
      intervals ranging from 3-46 months (mean 15.3 months). Patient records were
      retrospectively reviewed for surgical complications, soft tissue reactions,
      infections, and implant failures. The total success rate of cranial implantation
      in the study group was 92.9% (106/114). Surgical complications occurred in three
      of the 32 patients (9.3%). All cranial implants were successfully reconstructed
      after integration. Seven percent of the implants failed after initial integration
      was successful. The rate of significant soft tissue reactions or frank infection
      observed among the implanted patients was 6.1%. Titanium cranial implants coupled
      with custom prosthetic reconstruction offer an excellent alternative to
      traditional surgical techniques in the reconstruction of acquired or congenitally
      absent facial structures. Predictability, prosthetic adaptability, as well as
      superior aesthetics are major advantages to this technique when compared to
      traditional surgical reconstructive techniques.

PMID- 17003618
TI  - The inter-relationship between mandibular autorotation and maxillary LeFort I
      impaction osteotomies.
AB  - The purposes of the present investigation were to: 1)locate the instantaneous
      rotation center of mandible autorotation during maxillary surgical impaction; 2)
      identify the discrepancies between the resultant mandibular position following by
      maxillary surgical impaction and presurgical predictions, which use the
      radiographic condylar center as the rotation center for mandibular autorotation;
      and 3)find the interrelation between the magnitude of maxillary surgical
      impaction and the sagittal change of mandible. Ten patients underwent maxillary
      LeFort I impaction without concomitant major mandibular ramus split osteotomies
      were included. The preoperative (T0) and postoperative (T1) lateral cephalograms
      were used to evaluate the surgical changes and locate the center of rotation of
      mandibular autorotation with Reuleaux method. Prediction errors were measured by
      comparing the predicted (Tp) and postoperative (T1) cephalometric tracings. The
      magnitude of the maxillary surgical impaction was compared to the positional
      changes of mandible after mandibular autorotation with correlation and regression
      analysis. The results demonstrated that the centers of mandibular autorotation
      located 2.5 mm behind and 19.6 mm below the radiographic condylar center of the
      mandible in average with large individual variations. By using the radiographic
      condylar center of the mandible to predict the mandibular autorotation would
      overestimate the horizontal position of chin by 2 mm and underestimate the
      vertical position of chin by 1.3 mm following an average of 5 mm surgical
      maxillary impaction. The magnitude of maxillary impaction was highly and
      positively correlated to the horizontal displacement of chin position. The
      rotation centers of mandibular autorotation following by maxillary LeFort I
      impaction osteotomies might not usually locate at the radiographic condylar
      center of the mandible also with large individual variations in their positions.
      Surgeons and orthodontists should be aware of the horizontal and vertical
      discrepancies of chin positions while planning a two-jaw surgery by using the
      radiographic center of mandibular condyle as the rotation center in mandibular
      autorotation.

PMID- 17003619
TI  - Permanence of diced cartilage, bone dust and diced cartilage/bone dust mixture in
      experimental design in twelve weeks.
AB  - Bone dust and diced cartilage are used for contour restoration because their
      minimal donor site morbidity. The purpose of this study is to investigate
      permanence of bone dust, diced cartilage and bone dust/diced cartilage mixture in
      rabbits over 12 weeks. New Zealand white rabbits were used for this study. There
      were three groups in the study: Group I: 1 mL bone dust. Group II: 1 mL diced
      cartilage. Group III: 0.5 mL bone dust + 0.5 mL diced cartilage mixture. They
      were placed into subcutaneous tissue of rabbits and removed 12 weeks later. The
      mean volumes of groups were 0.23 +/- 0.08 mL in group I, 0.60 +/- 0.12 mL in
      group II and 0.36 +/- 0.10 mL in group III. The differences between groups were
      found statistically significant. In conclusion, diced cartilage was found more
      reliable than bone dust aspect of preserving its volume for a long period in this
      study.

PMID- 17003620
TI  - Scanning electron microscope and micro-CT evaluation of cranial sutures in health
      and disease.
AB  - Current knowledge of suture biology has been ascertained as a result of
      morphological studies of normal cranial sutures (and rarely those undergoing
      craniosynostosis). These were initially undertaken often using histological
      investigations, or more recently using CT scans, as investigative tools, but have
      often used animal models. However, recent technological advances have provided
      the potential to refine our understanding of the ultrastructure by the use of new
      advanced scanning technology, which offers the possibility of more detailed
      resolution. Our aim was to undertake detailed scans of normal, fusing and fused
      sutures from patients with craniosynosotosis affecting different sutures, to
      study the detailed structure at different stages of the fusion process using a
      modern micro-CT scanner and a microanalytical scanning electron microscope. We
      wished to include in our study all the human sutures because previous studies
      have mostly been undertaken using the sagittal suture. Ten sutures from seven
      patients have revealed a complex ultra-structural arrangement. The different
      patterns of bone ridging seen on the ectocranial and endocranial surfaces of the
      fused sagittal suture were not repeated on closer inspection of either fused
      coronal or lambdoid sutures. Elemental analysis confirmed that the amount of
      calcium increased and the amount of carbon decreased as sampled areas moved away
      from the suture margin. We conclude that scanning allowed detailed assessment and
      revealed the complex arrangement of the structure of the human cranial sutures
      and those undergoing the process of craniosynostosis, with some differences in
      final structure depending on the affected suture.

PMID- 17003621
TI  - The effect of high temperature intraoperative molding on bioabsorbable PLLA-PGA
      craniofacial fixation.
AB  - Bioabsorbable internal fixation has become an established part of the surgeons'
      armamentarium. There are several unique aspects of bioabsorbable polymers that
      can enhance their versatility. One of these is the application of heat to adapt
      the implant. Hot-tip cautery has been used for years to cut and otherwise
      customize bioabsorbable implants intraoperatively. As the tips of these devices
      can reach temperatures of over 1,000 degrees C, there is the potential that such
      practice can modify the degradation properties of these polymers. This study was
      performed to better understand the extent to which this potential exists. Screw
      heads of an 82:18 poly-L-lactic acid and poly-glycolic acid copolymer were
      modified by repeated passage of a hot-tip cautery wire, deforming the hex
      geometry to that of a ball. There was no significant difference between the glass
      transition temperature (approximately 59 degrees C) and inherent viscosity
      (approximately 1.45 dL/g) of treated and untreated screw heads, indicating no
      overall change in these properties throughout the mass of the screw head.
      Additionally, these properties were measured and comparisons made between the
      treated screw heads and untreated plates made of the same polymer during 28-day
      exposure to an in vitro bath (pH 7.4, 37 degrees C). The glass transition
      temperature and inherent viscosity exhibited declines during this period, with no
      significant differences between the two groups. Collectively, these results
      suggest that hot-tip cautery results in no substantial changes in the degradation
      characteristics of this polymer.

PMID- 17003622
TI  - Closure of rabbit calvarial critical-sized defects using protective composite
      allogeneic and alloplastic bone substitutes.
AB  - This study evaluated the repair of critical-sized cranial vault defects in thirty
      New Zealand white rabbits using various allogeneic and alloplastic bone
      substitutes designed to provide mechanical protection to the brain as well as
      osteoinductivity. The strategies employed included demineralized bone matrix
      (DBM), a putty used in combination with a rigid resorbable plating system as a
      protective covering and calcium phosphate cement (CPC) combined with native
      partially purified bone morphogenetic protein (BMP). Bilateral critical-sized
      defects measuring 15 mm in diameter were created in the parietal bones of 30
      adult male New Zealand white rabbits. They were divided into three groups with
      ten animals in each. Group 1 had one defect left unfilled as a control while
      autogenous bone was placed in the defect on the other side. In Group 2 a rigid
      resorbable copolymer membrane, Lactosorb (Lorenz Surgical, Jacksonville,
      Florida), was placed over both defects to cover them and protect the underlying
      tissues. The pericranial aspect of one defect was left unfilled while the other
      defect was filled with DBM putty. Group 3 had a CPC, Mimix (Lorenz Surgical,
      Jacksonville, Florida), placed into one of the defects while the defect on the
      other side was filled with the same CPC in combination with BMP in a
      concentration of 25 mg/mL. Bone healing was assessed clinically,
      radiographically, and histomorphometrically. All unfilled controlled defects, the
      defects covered with the resorbable Lactosorb membrane and those filled with
      calcium phosphate cement alone, healed with a fibrous scar. Defects reconstructed
      with DBM putty in combination with the resorbable Lactosorb membrane and calcium
      phosphate in combination with BMP healed with bone bridging the entire defect.
      This was obvious radiographically where the defects appeared completely filled
      with a dense radiopaque tissue. Histological analysis demonstrated that specimens
      where DBM putty was used in combination with the resorbable Lactosorb membrane
      had 67.7% new bone fill at 6 weeks and 84.0% at 12 weeks. Resorption of DBM
      particles was evidenced by the presence of osteoclastic activity and by the
      significant decrease in the size of the demineralized bone particles. In the
      calcium phosphate groups where BMP was added to the bioimplant there was 45.8%
      new bone formation at 12 weeks. The utilization of a composite consisting of DBM
      with resorbable Lactosorb membrane or a composite of calcium phosphate cement
      composite with BMP promoted complete closure of critical-sized calvarial defects
      in New Zealand white rabbits with viable new bone at 12 weeks. The complete bone
      bridging observed with these composites suggests that they could be used to
      enhance the protection of intracranial contents following craniofacial surgical
      procedures.

PMID- 17003623
TI  - Effect of FGF and polylactide scaffolds on calvarial bone healing with growth
      factor on biodegradable polymer scaffolds.
AB  - Repair of bone defects remains a major concern in reconstructive surgery.
      Synthetic biodegradable polymers have been used as scaffolds for guided bone
      regeneration. Fibroblast growth factors (FGFs) promote cell growth,
      differentiation, and tissue maintenance factors. They can stimulate the
      proliferation of osteogenic cells and chondrocytes, and also promote
      angiogenesis. Acidic and basic fibroblast growth factors (FGF-1 and FGF-2,
      respectively) are the best known members of this protein family. To evaluate the
      healing of experimental bone defects using poly-L/D-lactide (PLDLA) 96/4
      scaffolds and FGF-1, 18 adult rats were operated on. A 6-mm diameter critical
      size defect (CSD) was made in the calvarial bone of each rat. The animals were
      divided into three treatment groups: 1) Neither scaffold nor FGF was used
      (control group); 2) scaffold only; and 3) scaffold with FGF-1. Follow-up time was
      eight weeks. Samples were embedded in methylmethacrylate and 5-microm thick
      sections from the middle of each specimen were stained with modified Masson
      Goldner method. The shape and size of defects were evaluated radiologically. New
      bone formation was measured histologically and histomorphometrically.
      Radiologically, in the control group the shape of the defects changed from round
      to oval and edges were blunt. In the other groups the defects were round with
      sharp edges. Histomorphometrically, mean surface area of bone trabeculae was 1.05
      mm (SD +/- 0.25) in group 1 (no implant), 1.35 mm (SD +/- 0.52) in group 2
      (implant) and 0.79 mm (SD +/- 0.34) in group 3 (implant and FGF-1). Histological
      examinations revealed no or little osteoid in the groups 1 and 2, whereas in the
      group 3 samples had little or moderate new bone formation. Accordingly, no clear
      benefit of using knitted PLDLA scaffolds combined with FGF-1 on the healing of
      calvarial critical size defects in rats could be demonstrated.

PMID- 17003624
TI  - Transport distraction osteogenesis using nitinol spring: an exploration in canine
      mandible.
AB  - Some experiments in rabbits have presented the potential feasibility of using
      shape memory alloy spring for continuous distraction osteogenesis. To confirm the
      effectiveness of such method, we established canine models for the exploratory
      experiments of transport distraction osteogenesis using nitinol springs. Simple
      devices, including an internal 60-mm long sinusoid-shaped nitinol springs were
      used in the study. All dogs needed only one operation. In the operation,
      osteotomy was performed to create a 40-mm unilateral segmental mandibular body
      defect and a tooth-bearing transport bone disc. After reconstructive fixation of
      the remnant mandible, the spring was constricted and anchored across the
      distraction gap to activate transport distraction immediately. At the second
      experimental stage, an ePTFE sheet was further fixed to protect the defect and
      distraction gap before closing the incision. Control dogs underwent the same
      operation except for anchoring of the spring to examine the spontaneous bone
      regeneration. Automatic bone transportation, as a gradual slowdown process, was
      observed under the effect of the spring. The transport disc could get to the
      opposite side of the defect, or stopped halfway when ePTFE sheet intervened.
      Mandibular reconstruction was achieved in all these dogs and better in dogs with
      sheet protection. No integrated bone mass was found in the defect of control
      dogs. The study further proves that continuous distraction osteogenesis using
      nitinol springs is a practical technique, although the devices need more
      improvement for better control of the process of distraction and the quality of
      regenerated bone.

PMID- 17003625
TI  - Self-reinforced ciprofloxacin-releasing polylactide-co-glycolide 80/20 inhibits
      attachment and biofilm formation by Staphylococcus epidermidis: an in vitro
      study.
AB  - We have observed the efficiency of antibiotic-releasing polylactide-co-glycolide
      (PLGA) 80/20 in preventing Staphylococcus epidermidis attachment and biofilm
      formation in vitro. The aim of the present study was to evaluate the effect of
      self-reinforced (SR) implants with enhanced antibiotic release on bacterial
      attachment and biofilm formation rates, and also on growth inhibition of
      Staphylococcus epidermidis. Cylindrical SR-PLGA+AB specimens (length 30 mm,
      diameter 3 mm) were examined by scanning electron microscopy (SEM) for attachment
      of S. epidermidis ATCC 35989 on biomaterial surface and formation of biofilm,
      after incubating with bacterial suspension of ca. 10 cfu/mL for 1, 3, 7, 14 and
      21 days. SR-PLGA and SR-PLGA+AB implants were tested on agar plates by measuring
      the inhibition distance around implants. On the surface of SR-PLGA+AB, at days 1,
      3, 7, 14 and 21, the percentage of areas with not a single bacteria attached, was
      88.6%, 71.1%, 73.7%, 73.7%, and 68.4%, respectively. On the areas where bacteria
      were detected, the number of bacterial cells remained low during whole study
      period, and no significant increase by time was seen. There was no biofilm
      observed on 97-99% of the examined areas during the whole study period on SR
      PLGA+AB. In agar plates, the SR-PLGA+AB showed inhibition of bacterial growth,
      with (mean) 53.2 mm diameter of inhibition area with peeled implants and 50.5 mm
      with non-peeled implants. There was no inhibition seen around implants without
      ciprofloxacin. Bioabsorbable ciprofloxacin-releasing self-reinforced PLGA (SR
      PLGA+AB) was superior to plain SR-PLGA in preventing bacterial attachment,
      biofilm formation, and also the growth of Staphylococcus epidermidis.

PMID- 17003626
TI  - New osteotomies for midface advancement in patients with Crouzon syndrome.
AB  - In some patients with Crouzon's syndrome the typical midface advancement can
      produce an excessive nasal protrusion which calls for subsequent rhinoplasty.
      Proposed modification of classical Le Fort III procedure consists in midface
      osteotomy and external distraction without median orbital walls and nasal
      component. Limited surgical approach through vestibular incision and split lower
      eyelids makes the operation quite easy and less extensive. So far, three adult
      patients were successfully treated according to described modality.

PMID- 17003627
TI  - Simultaneous hybrid of maxillary Le Fort I halo distraction and mandibular set
      back for patients with severe cleft jaw deformity.
AB  - One of the surgical tactics and retrospective chart review of clinical cases are
      described for severe maxillo-mandibular discrepancy. The recently developed Le
      Fort I Halo distraction combined with mandibular sagittal splitting osteotomy is
      initially carried out simultaneously. Materials include six adult patients
      revealing severe jaw deformity with mandibular prognathism somehow ranging from
      17-19 years of age. The required adjustment of the maxillo-mandibular discrepancy
      ranged from 14-23 mm to obtain the preferred occlusion. The simultaneous
      combination of over 10-mm maxillary Le Fort I Halo distraction with mandibular
      set-back secured rigidly by sagittal splitting was accomplished. The amount of
      mandibular set-back ranged from 4-6 mm. The amount of maxillary Le Fort I halo
      distraction ranged from 10-17 mm (Table I). The retention period of the halo
      brace was 21-22 days. In addition, the Delair type of face mask was used for 3-4
      months as a night splint for consolidation after removal of the halo brace.
      Satisfactory maxillary distraction and mandibular set-back as planned
      preoperatively was obtained in all six cases. No particular postoperative
      complications were noticed. Compared with standard Le Fort I advancement for
      cleft patients, more advancement can be obtained easily with halo distration,
      particularly in cases where a large amount of advancement > 10 mm is required.
      This combination is worthwhile for a severe cleft jaw deformity, and is an
      alternative for standard double jaw osteotomy.

PMID- 17003628
TI  - Calcified cephalohematoma: classification, indications for surgery and
      techniques.
AB  - While calcified cephalohematoma is eminently correctable, a clear description of
      indications for surgery and surgical techniques are currently lacking in the
      literature. In this paper we propose a simple classification and an algorithm for
      the management of cephalohematomas. Three patients were treated for large
      calcified parietal cephalohematomas. Craniectomy and cranioplasty were performed
      with excellent outcome. Cranioplasty was performed with the cap radial
      craniectomy technique in two patients and the flip-over bull's-eye technique in
      one patient. The literature was reviewed on this entity and an algorithm based on
      the timing of presentation, extent of calcification and type of calcified
      cephalohematoma is proposed. Aspiration and compressive dressings can be used for
      early, incompletely calcified cephalohematomas. Calcified cephalohematoma causing
      significant distortion of the calvarium requires surgical correction and is
      classified as Types 1 or 2 depending on the contour of the inner lamella. Type 1,
      with a normal contoured inner lamella, can be corrected by ostectomy of the outer
      lamella. Type 2 calcified cephalohematoma has a depressed inner lamella.
      Elevation of the inner lamella is necessary and the cap radial craniectomy
      technique can be used. We describe a novel technique, the flip-over bull's-eye
      techniques as an alternative technique for Type 2 lesions in selected patients.
      In conclusion, calcified cephalohematomas can safely be treated surgically with
      excellent outcome. It is hoped that this algorithm will serve as a useful and
      logical guide in decision making for the management of this condition.

PMID- 17003629
TI  - Prevention of temporal depression that follows fronto-orbital advancement for
      craniosynostosis.
AB  - Contour abnormalities presenting after fronto-orbital advancement for
      craniosynostosis are common. Often there is bilateral temporal depression, the
      result of leaving a coronal bony gap posterior to the advanced segments. The
      authors present techniques to prevent this temporal depression by utilizing full
      thickness bone grafts for structural support in the inferior coronal defects, and
      cortico-cancellous graft in the remaining superior coronal and parietal donor
      defects. Prior to contouring and repositioning the frontal elements, a hand
      driven Hudson brace and D'Ericco bit is used to harvest cortico-cancellous bone
      "mush" from the endo- and ectocortical surfaces. The bandeau and frontal elements
      are advanced and secured, and the resultant coronal gap is measured. Full
      thickness cranial bone grafts are harvested from the parietal regions (near the
      vertex) and secured in the coronal defect behind the frontal elements. The
      temporalis muscle is rotated, advanced, and secured to the bandeau. Bone mush is
      used to fill the remaining superior coronal and donor site defects.
      Representative case examples are presented.

PMID- 17003630
TI  - Free rectus abdominis myocutaneous flap with anterior rectus sheath to provide
      the orbital support in globe-sparing total maxillectomy.
AB  - Reconstruction after total maxillectomy with preservation of the orbital contents
      is technically more challenging than when the maxillectomy is combined with
      orbital exenteration. It results in severe complications if the orbital content
      is not supported. We would like to introduce a new technique using free rectus
      abdominis myocutaneous (RAM) flap with anterior rectus sheath to support the
      orbital content in a patient who underwent globe-sparing total maxillectomy. The
      large resection of the recurrent maxillary peripheral nerve sheath tumor was
      performed in a 34-year-old male patient. Right free RAM flap was harvested
      simultaneously with the tumor resection. The anterior sheath of upper portion of
      the rectus muscle was also incorporated into the flap. The free edge of the upper
      anterior rectus sheath was anchored to three different points: Lateral rim,
      medial rim and the posterior remnant of the bony orbital floor with non
      absorbable suture. Consequently, orbital support was achieved with well
      vascularized, thin, strong fascia with smooth surface. Right facial artery and
      vein were chosen as recipient vessel. Duration of the operation was 5.5 hours.
      Postoperative period was uneventful. Six months after the surgery, the right eye
      was in good position without inferior dystopia. Eyeball movement could be done
      without restriction. The patient also denied diplopia. Reconstruction of globe
      sparing total maxillectomy defects with free RAM flap with anterior rectus sheath
      has several advantages that enable the reconstructive surgeon to solve the
      multiple complex reconstructive task with one flap: 1) elimination of the
      secondary donor site morbidity; 2) more simply addressing the challenging task of
      the eye support than the other techniques; 3) obliterating the maxillectomy
      defect and closing the palate; 4) restoring the large skin defect; and 5)
      reducing the operation time. It is difficult to conclude that this technique is
      the best choice in such cases based on a report of the single case. However,
      presented technique should be kept in mind as a practical and effective
      reconstructive option in cases that have underwent the total maxillectomy with
      the preservation of the orbit.

PMID- 17003631
TI  - Vector alignment in maxillary distraction osteogenesis.
AB  - Maxillary distraction osteogenesis is an alternative treatment of cleft patients
      with severe maxillary hypoplasia. The aim of this paper is to present the
      combined surgical/orthodontic treatment of a cleft lip and palate patient and to
      evaluate the maxillary distraction procedure and the distraction vector in high
      Le Fort I osteotomy.

PMID- 17003632
TI  - Bilateral congenital trigeminal sensorimotor neuropathy presents as a severe open
      bite malocclusion.
AB  - Trigeminal neuropathy is commonly seen as a disorder of sensation in the
      distribution of the fifth cranial nerve. An 18-year-old girl was referred to our
      hospital because of a severe anterior open-bite deformity with a long face after
      presurgical orthodontic treatment. Surgical plan was maxillary posterior
      impaction with anterior advancement, mandibular setback operation, and
      genioplasty with vertical chin reduction in one stage. One month after surgery
      she had still difficulty closing her mouth. With the help of her hands, she could
      close her mouth fully on normocclusion. Weakness of the jaw-closing muscles was
      confirmed with muscle testing. She had impaired sensation to light touch and
      pinprick in the distribution of the maxillary and mandibular divisions of the
      bilateral trigeminal nerves. T1-weighed MRI of the brain showed bilaterally
      atrophy of the muscles innervated by the trigeminal motor nerve (i.e., the
      masseter, medial and lateral pterygoids, and temporalis muscles). We thoroughly
      evaluated our patient through history and clinical, laboratory,
      electrophysiological, and radiological examinations. The motor and the sensory V2
      and V3 branches of the trigeminal nerve were congenitally damaged. As far as we
      know, this case is the first bilateral congenital trigeminal sensorimotor
      neuropathy presented with maxillo-mandibular and a severe open-bite deformity.

PMID- 17003633
TI  - Giant pleomorphic adenoma of soft palate leading to obstruction of the
      nasopharyngeal port.
AB  - Pleomorphic adenoma is the most common tumor of minor salivary glands, but it is
      rarely located in the soft palate. It is generally a small mass at the time of
      diagnosis, but if it is neglected it can rarely become larger, leading to
      obstructive symptoms such as snoring, hypernasal speech, and dysphagia. Surgical
      removal of the mass is curative. In this paper, we present a case of an unusually
      large pleomorphic adenoma of the soft palate leading to snoring and hypernasal
      speech. The defect that resulted from the excision of the mass is covered with a
      uvular flap.

PMID- 17003634
TI  - Caution in treating transsphenoidal encephalocele with concomitant moyamoya
      disease.
AB  - A basal encephalocele is a rare congenital malformation involving a cranial bone
      defect and cystic-like herniation through the defect. Moyamoya is a rare
      cerebrovascular disease of unclear etiology involving occlusion of the distal
      internal carotids and formation of collateral vascular networks. Both diseases
      have been correlated with optic disc anomalies, hypopituitarism, and midfacial
      defects. We present a case of a 2-year-old boy with a midline facial cleft who
      underwent surgical correction of a basal encephalocele. His moyamoya disease may
      have contributed to a vascular complication. There is growing evidence indicating
      an overlap in disease profiles for these two rare diseases. In addition,
      molecular evidence indicates elevated levels of fibroblast growth factor and
      transforming growth factor in both diseases, suggesting common molecular
      pathways.

PMID- 17003635
TI  - Mature teratoma presenting as a scalp mass in a newborn.
AB  - Neonatal teratomas are rarely located in the scalp. We present a 10-day-old
      female newborn with mature teratoma of the occipital scalp. The tumor mass, which
      had no intracranial extension, was excised completely when the patient was 14
      days old. The scalp defect was reconstructed with local flaps. No recurrence was
      detected 3 months after the surgery. Because the patient did not return for
      routine follow-up 6 months after surgery, we called the parents and learned that
      the patient had suddenly died. A necropsy to explain the cause of death was not
      available.

PMID- 17003636
TI  - Upper eyelid reconstruction with a hard palate mucosa-lined bipedicled
      myocutaneous flap.
AB  - The upper eyelid is very difficult to reconstruct because smooth opening and
      closure of the eyelid must be maintained. A patient is presented in whom a hard
      palate mucosa-lined bipedicled myocutaneous flap containing innervated
      orbicularis oculi was used to successfully reconstruct a subtotal upper eyelid
      defect. Good functional and aesthetic results were achieved. This method may be a
      good alternative for reconstruction of large upper eyelid defects.

PMID- 17003637
TI  - Neglected squamous cell carcinoma of the frontal area: a clinical report.
AB  - Neglected skin carcinomas are not very often in our days. It is known that skin
      is the most common site of malignancy Squamous cell carcinoma (SCC) is the second
      most common malignancy of the skin. We report a combined surgical treatment in an
      unusual case of a squamous cell carcinoma (T4 n0 m0) localized on scalp,
      presented primarily as a frontal ulcerative bloody mass, with no palpable lymph
      nodes and a whole body negative computed tomography. Three months after the first
      surgical procedure, the tumour reappeared presenting left frontal lobe invasion.
      A combined surgical management (neurosurgery and plastic surgery) was realized,
      in order to remove the tumour and to cover the defect. Three months later the
      tumour recrudesced invading the left antrum, infiltration of remained parotid
      gland and an ipsilateral mandible osteolysis, besides a 2 cm size distal
      metastasis at the right upper lobe of the lung was revealed. This article,
      through case report and a brief review of the literature, offers criteria for the
      surgical treatment of SCC that arise on the scalp.

PMID- 17003638
TI  - Total lower eyelid reconstruction using paranasal flap.
AB  - The main aim of this study is to evaluate the advantages, disadvantages, and
      aesthetic results of the total lower eyelid reconstruction with paranasal flap.
      The other reconstruction methods are also revisited.Ten patients, who were
      operated for the reconstruction of total lower eyelid defects between November,
      1999 and April, 2005 in our department were included in this study. The total
      lower eyelid defects of all patients were reconstructed using paranasal flap for
      anterior lamella and chondromucosal, chondrocutaneous or mucosal graft for
      posterior lamella. Follow-up time was ranged between 3-35 months. The advantages,
      disadvantages and complications were defined and aesthetic results of the
      patients were also evaluated by using a questionnaire which was filled by
      patients at third month after reconstruction. All flaps and grafts survived,
      partial or total necrosis was not encountered but one patient with ectropion had
      a secondary reconstructive procedure. The aesthetic results of the patients were
      also satisfactory. The paranasal flap is very reliable and safe method for total
      lower eyelid reconstruction.

PMID- 17003639
TI  - Nasal adenoid cystic carcinoma with intracranial extension.

PMID- 17003640
TI  - Pancreatic imaging: current and emerging technologies.
AB  - This review discusses the current imaging modalities for the diagnosis and
      staging of solid and cystic pancreatic lesions and for the assessment of acute
      and chronic pancreatitis, and the future role of emerging technologies in the
      management of pancreatic diseases. Multidetector row spiral computed tomography
      is superior to conventional single-detector row spiral computed tomography in the
      detection and staging of pancreatic adenocarcinoma. Positron emission tomography
      is a sensitive but relatively nonspecific diagnostic modality. Positron emission
      tomography-computed tomography fusion may improve the staging accuracy for
      pancreatic cancer. Echo-enhanced ultrasound may have an emerging role in
      evaluating pancreatic masses. Endoscopic ultrasound with fine needle aspiration
      for cytology is the single best method for diagnosis and staging of nonmetastatic
      pancreatic cancer with a high accuracy for determining tumor resectability. In
      acute pancreatitis, a modification of the standard computed tomography severity
      index, which places greater emphasis on extrapancreatic complications, has shown
      superior correlation with various patient outcome measures. Endoscopic retrograde
      cholangiopancreatography is still the test of choice for morphological evaluation
      of chronic pancreatitis, whereas magnetic resonance cholangiopancreatography
      offers a noninvasive alternative in selected patients. Endoscopic ultrasound can
      be useful for detecting early chronic pancreatitis. Secretin-stimulated imaging
      techniques may eventually provide a noninvasive method of reliably assessing
      pancreatic exocrine function.

PMID- 17003641
TI  - Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with
      pancreatitis.
AB  - OBJECTIVES: Chronic pancreatitis is a progressive inflammatory disorder leading
      to irreversible exocrine and/or endocrine impairment. It is well documented that
      mutations in the cationic trypsinogen (PRSS1) gene can cause hereditary
      pancreatitis. Mutations in the cystic fibrosis transmembrane conductance
      regulator (CFTR) and the serine protease inhibitor Kazal type 1 (SPINK1) genes
      are also associated with pancreatitis. METHODS: We analyzed 381 patients with a
      primary diagnosis of chronic or recurrent pancreatitis using the Ambry Test:
      Pancreatitis to obtain comprehensive genetic information for the CFTR, SPINK1,
      and PRSS1 genes. RESULTS: The results identified 32% (122/381) of patients with
      166 mutant CFTR alleles, including 12 novel CFTR variants: 4375-20 A>G, F575Y,
      K598E, L1260P, G194R, F834L, S573C, 2789 + 17 C>T, 621+83 A>G, T164S, 621+25 A>G,
      and 3500-19 G>A. Of 122 patients with CFTR mutations, 5.5% (21/381) also carried
      a SPINK1 mutation, and 1.8% (7/381) carried a PRSS1 mutation. In addition, 8.9%
      (34/381) of all patients had 1 of 11 different SPINK1 mutations. Another 6.3%
      (24/381) of the patients had 1 of 8 different PRSS1 mutations. Moreover, 1.3% of
      the patients (5/381) had 1 PRSS1 and 1 SPINK1 mutation. A total 49% (185/381) of
      the patients carried one or more mutations. CONCLUSIONS: Comprehensive testing of
      the CFTR, PRSS1, and SPINK1 genes identified genetic variants in nearly half of
      all subjects considered by their physicians as candidates for genetic testing.
      Comprehensive test identified numerous novel variants that would not be
      identified by standard clinical screening panels.

PMID- 17003642
TI  - Recent randomized controlled trials in pancreaticoduodenectomy.
AB  - OBJECTIVES: To analyze and summarize the recent randomized controlled trials
      (RCTs) investigating pancreaticoduodenectomy (PD). METHODS: A MEDLINE search was
      performed to identify prospective RCTs on PD published during the last decade.
      Eligible RCTs were analyzed using the following items: publication year,
      geographical area, study theme, sample size, and multicenter study. Moreover, the
      quality of each RCT was evaluated. RESULTS: Thirty-four articles were eligible
      for review. One to 6 RCTs have been carried out annually during the recent 10
      years. Geographically, 15 trials were performed in Europe, 10 trials in North
      America, and 9 in Asia. Studies concerning postoperative complications in the
      early postoperative period such as pancreatic fistula and delayed gastric
      emptying have been most frequent. Randomized controlled trials comparing
      anastomotic procedures for the remnant pancreas, standard PD versus PD with
      extended lymphadenectomy, and PD versus pylorus-preserving PD follow in
      descending order. The average sample size has been 117, and 10 RCTs had sample
      size less than 50. The rate of multicenter studies among all RCTs is 21%, with
      the rate in the most recent 5 years having increased 2-fold compared with that in
      the earlier period. Concerning the quality of RCTs, calculation of sample size
      was described in only 14 RCTs and intention to treat analysis was performed in 26
      RCTs. CONCLUSIONS: This study reviewed 34 RCTs on PD performed all over the
      world. Although the quality of every RCT was not satisfactory, high-grade
      evidence obtained by these RCTs should be applied in clinical settings to improve
      surgical quality and quality of life for each patient.

PMID- 17003643
TI  - Reappraisal of the clinical significance of tumor size in patients with
      pancreatic ductal carcinoma.
AB  - OBJECTIVES: Recent advances in diagnostic modalities have made it possible to
      detect small pancreatic ductal carcinoma and to increase the number of resected
      cases. However, the postoperative prognosis remains dismal. METHODS: Prognostic
      factors after pancreatectomy were retrospectively examined in 173 patients with
      small pancreatic ductal carcinomas (<or=40 mm), and the size threshold for
      defining small pancreatic cancer as an early and curable disease was
      investigated. RESULTS: A Cox proportional hazard survival analysis indicated that
      no lymph node involvement and curative resection were important independent
      predictors of long-term survival. The incidence of lymph node metastasis was
      significantly lower in patients with tumor diameters of 20 mm or less (P <or=
      0.001). Tumors with diameters of 15 mm or less were statistically associated with
      lower extension of local tumor spreading (P = 0.001) and less advanced stage (P =
      0.011). The 5-year survival rate and the median survival term in patients with
      tumor diameters of 15 mm or less were 75% and 62 months, respectively, which were
      significantly better than those in patients with tumor diameter between 21 and 40
      mm (P = 0.02). CONCLUSIONS: A small tumor size is not always a guarantor of
      localized disease. However, survival after pancreatectomy is significantly
      favorable when the tumor diameter is 15 mm or less. A tumor diameter of 15 mm is
      recommended as the cutoff size as small pancreatic cancer because tumors with
      diameters between 16 and 20 mm should be considered comparable with tumors with
      diameters between 21 and 40 mm.

PMID- 17003644
TI  - The ratio of metastatic/resected lymph nodes is an independent prognostic factor
      in patients with node-positive pancreatic head cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate the prognostic value of nodal
      involvement in resected adenocarcinoma of the pancreatic head. METHODS: For the
      period between 1980 and 2002, 96 patients underwent pancreaticoduodenectomy for
      pancreatic cancer. Lymph nodes were numbered and classified into groups according
      to the Japan Pancreatic Society rules. Metastatic lymph nodes were identified
      based on hematoxylin and eosin staining. RESULTS: Sixty-four (66.7%) patients had
      positive lymph nodes. The median number of metastatic nodes was 2 (95% confidence
      interval [CI], 1.0-3.0) and the median ratio of metastatic/resected nodes was
      9.7% (95% CI, 7.1%-14.4%). The median survival was 14.2 months (95% CI, 10.7
      17.7) and was significantly higher for node-negative than node-positive patients
      (27.9; 95% CI, 20.9-34.9 vs. 10.6; 95% CI, 8.7-12.5; P < 0.001). The Cox
      proportional hazards model, including all patients, demonstrated that nodal
      involvement (hazard ratio [HR], 1.461; 95% CI, 1.177-12.024), moderate or poor
      tumor differentiation (HR, 2.330; 95% CI, 1.181-6.949), and positive resection
      margins (HR, 3.838; 95% CI, 1.390-10.597) were independent negative prognostic
      factors. If the analysis was limited to node-positive patients, lymph node ratio
      of more than 20% (HR, 1.364; 95% CI, 1.116-2.599), moderate or poor tumor
      differentiation (HR, 3.393; 95% CI, 1.041-11.061), and positive resection margins
      (HR, 9.400; 95% CI, 2.235-39.536) significantly correlated with a poorer
      survival. CONCLUSIONS: Lymph node ratio seems to be a new promising prognostic
      factor in patients with respectable node-positive pancreatic head cancer.

PMID- 17003645
TI  - Preoperative carbohydrate antigen 19-9 is most predictive of malignancy in older
      jaundiced patients undergoing pancreatic resection.
AB  - OBJECTIVES: Given the increased detection of occult pancreatic neoplasms with
      modern imaging modalities, it is often difficult to determine the risk of
      malignancy before curative pancreatectomy. We reviewed patients who underwent
      pancreatectomy to determine factors predictive of malignancy with particular
      attention to the serum marker carbohydrate antigen 19-9 (CA19-9). METHODS: One
      hundred eighteen patients underwent radical pancreatectomy for malignant (n = 59)
      or benign (n = 59) pancreatic lesions. Demographic data, preoperative CA19-9
      levels (normal, <37 U/mL), and follow-up were obtained from patient charts.
      Logistic regression analysis was used to determine univariate and multivariate
      predictors of malignancy. RESULTS: Significant multivariate predictors of
      malignancy were increased CA19-9, age older than 50 years, and preoperative
      jaundice. The sensitivity and specificity of increased preoperative CA19-9 alone
      were 71% and 83%, respectively. The combination of age older than 50 years and
      jaundice was a more accurate predictor than CA19-9 (sensitivity, 76%;
      specificity, 92%). Increased CA19-9 was highly specific (97%) for malignancy in
      older jaundiced patients or when the preoperative level was greater than 150
      U/mL. CONCLUSIONS: Age and preoperative jaundice are more predictive of
      malignancy than CA19-9 alone unless levels are greater than 150 U/mL.
      Preoperative CA19-9 levels should be interpreted within the context of these
      other clinical factors.

PMID- 17003646
TI  - Validation of serum versus plasma measurements of chromogranin a levels in
      patients with carcinoid tumors: lack of correlation between absolute chromogranin
      a levels and symptom frequency.
AB  - OBJECTIVE: Chromogranin A (CGA) levels are used to confirm the diagnosis and
      monitor the course of patients with neuroendocrine tumors. Chromogranin A levels
      are significantly reduced when patients are acutely treated with octreotide;
      however, limited data are available that correlates octreotide long-acting
      repeatable (LAR) dose or steady state octreotide blood levels to the absolute
      value of serum or plasma CGA. METHODS: Plasma, serum, and clinical information on
      carcinoid syndrome symptoms were collected anonymously from 40 patients treated
      with long-term octreotide LAR therapy for carcinoid syndrome. RESULTS: We found a
      strong positive linear relationship exists between serum and plasma CGA levels (r
      = 0.9858, P < 0.0001). No correlation existed between plasma octreotide levels or
      LAR dose and the static, absolute plasma/serum CGA levels. Although, higher mean
      CGA values were seen in the group whose diarrhea was "not under optimal control"
      than for the group "under optimal control," these results did not reach
      statistical significance (P = 0.24). Contrary to our hypotheses, a statistically
      significant inverse relationship was found between the frequency of flushing and
      the CGA levels (P = 0.0372). Higher mean CGA values were observed in the "under
      optimal control" group with flushing symptoms. CONCLUSIONS: Either serum or
      plasma can be used to measure CGA levels. Absolute (static) CGA levels do not
      positively correlate with symptom intensity during LAR therapy. Dynamic (serial)
      measurements of CGA are necessary to monitor the effectiveness of medical or
      surgical therapy.

PMID- 17003647
TI  - Clinicopathologic study on pancreatic groove carcinoma.
AB  - OBJECTIVES: Pancreatic groove carcinoma usually presents with duodenal stenosis.
      This report describes the clinicopathologic features of 5 cases. METHODS: All the
      clinical and radiological features were reviewed retrospectively and analyzed to
      identify correlations with the histological findings. RESULTS: Vomiting was an
      initial symptom in all cases, but obstructive jaundice was not inevitable until
      the disease progresses. Hypotonic duodenography demonstrated severe postbulbar
      stenosis. Pathological findings of biopsy specimens showed no evidence of
      malignancy at the early stage. Computed tomography revealed a hypovascular mass.
      Magnetic resonance imaging indicated a hypointense mass on T1-weighted images and
      an isointense to slightly hyperintense mass on T2 images. Macroscopically, the
      stenosis seemed to be the result of a hard yellowish-white tumor invading the
      duodenal wall. Histopathologically, an adenocarcinoma arising from the groove
      infiltrated the submucosal layer of the duodenum circumferentially. No cancer
      cells were found in the mucosa at the early stage. The intrapancreatic common
      bile duct was involved at the advanced stage. CONCLUSIONS: We believe that these
      features resulted from the anatomical characteristics of the groove involvement
      and that the string stricture of the duodenum resulted from invasion of the
      groove tumor into the submucosal layer around the wall.

PMID- 17003648
TI  - Activation of nuclear factor kappa B and severe hepatic necrosis may mediate
      systemic inflammation in choline-deficient/ethionine-supplemented diet-induced
      pancreatitis.
AB  - OBJECTIVES: We hypothesized that hepatic injury is associated with severe acute
      pancreatitis (SAP) and may result in lung injury through nuclear factor kappa B
      (NF-kappaB)-dependent inflammatory mediators. The study characterizes the timing
      and determines the involvement of selected cytokines and chemokines in the
      pathogenesis of hepatocellular injury associated with SAP. METHODS: The SAP was
      induced in C57BL/6 mice by feeding a choline-deficient/ethionine-supplemented
      diet. The mice were killed at 12-hour intervals for 96 hours. Terminal
      deoxynucleotidyl transferase-mediated nick-end labeling staining was used to
      determine the extent of hepatic apoptosis. The NF-kappaB activation in nuclear
      protein extracts from liver tissue was measured using a sensitive RelA enzyme
      linked immunoadsorbent assay. Tumor necrosis factor alpha, interleukin 6,
      macrophage inflammatory protein (MIP) 2, and keratinocyte-derived chemokine (KC)
      levels in homogenates of liver and lung tissues were measured by enzyme-linked
      immunoadsorbent assay. The SAP-associated neutrophil lung inflammation was
      measured as tissue myeloperoxidase activity. RESULTS: The SAP and subsequent
      liver injury were confirmed by histological analysis and rises in plasma amylase
      and transaminase levels. Severe hepatocellular apoptosis was detected at 36 and
      48 hours after the diet initiation by terminal deoxynucleotidyl transferase
      mediated nick-end labeling staining (P < 0.05) and subsequently progressed to
      hepatic necrosis. Liver NF-kappaB activation was detected at 36 hours (P < 0.05)
      and followed by a sharp increase in hepatocellular levels of interleukin 6, MIP
      2, and KC at 72 hours and thereafter (P < 0.05). Levels of MIP-2 and KC in lung
      tissue were also elevated at 72 hours (P < 0.05) and closely correlated with
      increased myeloperoxidase activity and increased inflammatory cell infiltrate in
      the lung. CONCLUSIONS: Choline-deficient/ethionine-supplemented diet-induced SAP
      is accompanied with hepatocellular apoptosis and eventual necrosis. This injury
      is associated with the hepatic NF-kappaB activation leading to the production of
      NF-kappaB-dependent cytokines and chemokines in the liver, which may mediate the
      lung injury.

PMID- 17003649
TI  - Intrapancreatic axonal hyperbranching of dorsal root ganglia neurons in chronic
      pancreatitis model rats and its relation to pancreatic pain.
AB  - OBJECTIVES: Increase in number of intrapancreatic nerve bundles has been
      implicated in the generation of persistent pain in chronic pancreatitis. To
      examine the origin of these nerve fibers and the mechanisms linking neural
      morphological change to pain generation, we used neuronal tracing techniques in
      combination with immunohistochemistry in spontaneous chronic pancreatitis in the
      Wistar Bonn/Kobori (WBN/Kob) rats. METHODS: For retrograde tracing, horseradish
      peroxidase was injected into the pancreas, and labeled neurons in the sensory
      ganglia were counted. For anterograde tracing, biotinylated dextran amine was
      injected into the dorsal root ganglia (DRGs), and labeled intrapancreatic sensory
      fibers were histochemically assessed. For assessment of pain generation, we
      evaluated c-Fos-positive neurons in the spinal dorsal horn and behavioral changes
      of the animals. RESULTS: In WBN/Kob rats, the numbers of horseradish peroxidase
      labeled neurons were decreased in the DRGs, and the numbers of biotinylated
      dextran amine-labeled intrapancreatic nerve fibers and terminals were increased.
      Biotinylated dextran amine-labeled nerve fibers contained growth-associated
      protein 43. The number of c-Fos-positive neurons in the dorsal horn was also
      increased and was correlated with intrapancreatic growth-associated protein 43
      immunoreactivity. Grooming behavior was reduced in WBN/Kob rats, and this
      reduction was facilitated by exocrine stimulation. CONCLUSIONS: Axonal branching
      in DRG neurons innervating the pancreas increases in WBN/Kob rats, and these
      morphological changes are likely involved in pain generation in chronic
      pancreatitis.

PMID- 17003650
TI  - Transplantation of rat islets transduced with human heme oxygenase-1 gene using
      adenovirus vector.
AB  - OBJECTIVE: To investigate whether human heme oxygenase-1 (HO-1) gene has
      protective action on islets cultured in vitro, and to explore whether
      transduction of HO-1 gene to donor islets could enhance engrafted islets survival
      and suppress local lymphocytic infiltration in islet grafts. METHODS: Newly
      isolated rat islets were isolated from the Sprague-Dawley rats and were divided
      into 3 groups in vitro study as follows: enhanced green fluorescent protein
      (EGFP) group, islets transduced with adenovirus vectors containing EGFP gene
      using multiplicities of infection (MOI) = 2, 5, 10, and 20 to determine the
      transduction efficacy; HO-1 group, islets transduced with adenovirus vectors
      containing human HO-1 gene using MOI = 20; and control group, mock transduced
      islets. Flow cytometry was used to detect apoptotic cells after induction by
      recombinant human tumor necrosis factor-alpha (rTNF-alpha) and cycloheximide
      (CHX) for 48 hours. Diabetic recipients were randomly divided into the following
      groups: HO-1 group (n = 9), receiving islets transduced with recombinant
      adenovirus-HO-1; control group (n = 9), receiving mock transduced islets; and
      phosphate buffer solution (PBS) group (n = 6), receiving only 0.8 mL PBS. About
      1200 rat islet equivalents were transplanted into each recipient rendered by
      streptozotocin using the portal vein as transplant site. Allograft survival,
      apoptosis, and the state of lymphocytic infiltration were analyzed. RESULTS:
      After treatment with rTNF-alpha and CHX, the apoptotic ratio of islet cells was
      4.22% +/- 2.38% in the HO-1 group (MOI = 20), significantly lower than 23.81% +/-
      8.51% in the control group (P < 0.05), and 28.76% +/- 14.76% in the EGFP group
      (MOI = 20; P < 0.05). Maintenance of normoglycemia was prolonged in the HO-1
      group, indicated by results that islet survival time was 10.56 +/- 4.33 days
      significantly longer than that of untreated islets which was 5.33 +/- 4.18 days
      (P < 0.05). The lymphocytic infiltration degree in engrafted islets treated with
      HO-1 gene was lower than that in the control group. CONCLUSIONS: HO-1 gene
      overexpression in rat islets by adenovirus transduction can protect cultured
      islets against rTNF-alpha and CHX-mediated cytotoxicity. HO-1 gene has
      cytoprotective effects on engrafted islets, which could prolong engrafted islets
      survival in allogenic transplantation model, and diminish the degree of
      lymphocytic infiltration in islet grafts. These findings suggest a potential
      therapeutic application for HO-1 gene in improving islet survival/function in
      human islet transplantation.

PMID- 17003651
TI  - Induction of diabetes in cynomolgus monkeys with high-dose streptozotocin:
      adverse effects and early responses.
AB  - OBJECTIVES: Streptozotocin (STZ) has been widely used to induce diabetes in
      nonhuman primates, although it has been found difficult to achieve complete
      diabetes without serious adverse effects. We have investigated different types
      and dosages of STZ to find a way to safely induce complete diabetes in cynomolgus
      monkeys. METHODS: After adequate hydration, 10 monkeys received STZ. Five monkeys
      received conventional STZ (Sigma) at a dosage of 1250 mg/m ("high dose"; n = 4)
      or 60 mg/kg ("low dose"; n = 1; Group 1). Five monkeys received Zanosar STZ
      (Sicor Pharmaceuticals, Irvine, CA) at 150 mg/kg (high dose; n = 5; Group 2).
      RESULTS: High-dose Group 1 monkeys became completely diabetic (n = 4), but a
      protein-losing nephropathy was observed in 3 of the 4 monkeys. The monkey that
      received 60 mg/kg STZ failed to become fully diabetic (C-peptide, > 1.86 ng/mL).
      Group 2 (high-dose Zanosar-treated) monkeys became completely diabetic but with
      no apparent adverse effects. A triphasic blood glucose response to STZ was
      documented in all the high-dose STZ-treated monkeys. Low-dose STZ failed to
      result in a triphasic response. CONCLUSIONS: (1) High-dose Zanosar STZ induced
      diabetes safely in cynomolgus monkeys without adverse effects. (2) A triphasic
      blood glucose response suggested the complete induction of diabetes.

PMID- 17003652
TI  - Delayed response toward activation stimuli in pancreatic stellate cells.
AB  - OBJECTIVES: Pancreatic stellate cells (PSCs) are known to be crucially involved
      in the development of pancreatic fibrosis, a characteristic feature of chronic
      pancreatitis and pancreatic cancer. The key event in the pathogenesis of fibrosis
      represents a transition process of quiescent PSCs into a myofibroblastlike
      phenotype associated with cell activation in terms of proliferation and synthesis
      of profibrogenic substances. There is little information available regarding the
      dynamics of the complex processes initiated by an activating stimulus in
      quiescent stellate cells. METHODS: Using microarray analysis, we characterized
      the expression profiles during PSC activation caused by in vitro cultivation on
      days 2, 4, 7, and 14 after cell isolation. Activation status has been identified
      by the expression of the activation marker alpha-smooth muscle actin. Genes of
      interest were subjected to reverse transcription-polymerase chain reaction. To
      test biologic functions, the responsiveness of stellate cells toward the
      activators activin A and transforming growth factor-beta1 was investigated in
      dependence on the cell transition status. RESULTS: Our results revealed that
      freshly isolated (=quiescent) PSCs were refractory to stimuli for several days, a
      phenomenon that we referred to as delay phase. CONCLUSION: The retarded response
      could be considered a protection mechanism to prevent inappropriate stellate cell
      activation.

PMID- 17003653
TI  - Clinicopathologic features of two rare cases of mesenchymal metastatic tumors in
      the pancreas: review of the literature.
AB  - OBJECTIVES: A clinicopathologic presentation of 2 unusual cases of metastatic
      mesenchymal neoplasms in the pancreas. METHODS: The first case concerns a 26-year
      old man with a history of intracranial mesenchymal chondrosarcoma (since the age
      of 17), 2 left lung operations, and 3 right thigh operations. Distal
      pancreatectomy and splenectomy was performed because of suspicious mass in the
      pancreas. The second case concerns a 66-year-old woman with a history of uterus
      leiomyosarcoma (10 years ago) with left axillary and right femoral metastases.
      She underwent distal pancreatectomy and splenectomy because of suspicious mass
      measuring 4 x 4 cm, in the pancreatic body. RESULTS: In the first case, the
      pathological examination revealed a tumor measuring 3.8 x 3.5 cm and
      histologically compatible with mesenchymal chondrosarcoma, developing in a vessel
      lumen and invading into the pancreatic parenchyma. In the second case, the
      pathological examination showed metastatic leiomyosarcoma of high-grade
      malignancy. The incidence of metastatic pancreatic tumors has been reported to be
      only 1.6% to 3%. Most of these tumors were of epithelial origin, and the most
      common sites of the primary lesions were the lung, kidney, and gastrointestinal
      tract. CONCLUSIONS: The cases of metastatic uterus leiomyosarcoma and the
      metastatic intracranial chondrosarcoma are, to our knowledge, the first to be
      described.

PMID- 17003654
TI  - An unusual case of undifferentiated carcinoma in situ with osteoclast-like giant
      cells of the pancreas.
AB  - OBJECTIVES: We report an unusual case of undifferentiated carcinoma in situ with
      osteoclast-like giant cells (UC with OGCs) in a 68-year-old Japanese woman.
      METHODS: Preoperative examinations revealed an unidentifiable mass lesion within
      the main pancreatic duct (MPD) in the pancreatic head, accompanied by a dilated
      MPD distal to the mass lesion, which was suspected to be an intraductal papillary
      mucinous neoplasm of the main-duct type with acute pancreatitis because of an
      increased serum amylase level. A pancreaticoduodenectomy was performed. RESULTS:
      A pencil-like tumor occupied the lumen of the MPD of the pancreatic head without
      a visible pancreatic parenchymal mass. The intraductal tumor included a sheet of
      spindle cells intermingled with scattered OGCs and pleomorphic giant cells. A
      poorly developed glandular pattern was occasionally observed at the tumor
      periphery. These findings were consistent with conventional UC with OGCs.
      However, extraductal invasion was not found in an extensive histopathologic
      examination, although focal intraductal spreading into the epithelium of the
      first branch of the MPD was observed. CONCLUSIONS: Undifferentiated carcinoma
      with OGCs usually exhibits an invasive tumor at diagnosis and is associated with
      a poor outcome, but the patient is alive without recurrence 22 months after
      surgery. To our knowledge, this is the first reported case of UC in situ without
      evident extraductal invasion in English literature.

PMID- 17003655
TI  - Acinar cell cystadenocarcinoma of the pancreas in a 4-year-old child.

PMID- 17003656
TI  - Mucinous cystic tumor of the pancreas in a man: a rare case.

PMID- 17003657
TI  - Shingles-associated Pancreatitis.

PMID- 17003658
TI  - Autoimmune pancreatitis with autoimmune hemolytic anemia.

PMID- 17003659
TI  - Retraction. Reversal of diabetes by xenotransplantation of monkey pancreatic
      islets in rats: an ultrastructural study.

PMID- 17003660
TI  - A comparison of cognitive-behavioral therapy, sertraline, and their combination
      for adolescent depression.
AB  - OBJECTIVE: To evaluate cognitive-behavioral therapy, antidepressant medication
      alone, and combined CBT and antidepressant medication in the treatment of
      depressive disorders in adolescents. METHOD: Seventy-three adolescents (ages 12
      18 years) with a primary diagnosis of DSM-IV major depressive disorder, dysthymic
      disorder, or depressive disorder not otherwise specified were randomly allocated
      to one of three treatments. Treatment outcome measures were administered before
      and after acute treatment, and at a 6-month follow-up. Depression diagnosis was
      the primary outcome measure; secondary measures were self- and other report and
      clinician rating of global functioning. The trial was conducted at three
      community-based clinics between July 2000 and December 2002. Data analyses used
      an intent-to-treat strategy. RESULTS: Following acute treatment, all treatment
      groups demonstrated statistically significant improvement on outcome measures
      (depressive diagnosis, Reynolds Adolescent Depression Scale, Revised Children's
      Manifest Anxiety Scale, Suicidal Ideation Questionnaire), and improvement was
      maintained at follow-up. Combined cognitive-behavioral therapy and antidepressant
      medication was not found to be superior to either treatment alone. Compared with
      antidepressant medication alone, participants receiving cognitive-behavioral
      therapy alone demonstrated a superior acute treatment response (odds ratio =
      6.86; 95% confidence interval 1.12-41.82). Although cognitive-behavioral therapy
      was found to be superior to antidepressant medication alone for the acute
      treatment of mild to moderate depression among youth, this may have stemmed from
      the relatively low dose of sertraline used. CONCLUSIONS: All treatments led to a
      reduction in depression, but the advantages of a combined approach were not
      evident.

PMID- 17003661
TI  - Sertraline in children and adolescents with major depressive disorder.
AB  - OBJECTIVE: To explore time to first response and time to first persistent
      response of sertraline versus placebo and compare these parameters between
      children (6-11 years old, n = 177) and adolescents (12-17 years old, n = 199)
      with major depressive disorder. METHOD: A 10-week placebo-controlled treatment
      was followed by a 24-week open-label sertraline treatment. The double-blind
      studies were not powered to detect efficacy differences between age groups. A
      post hoc analysis explored time to first response and first persistent response
      using the Children's Depression Rating Scale-Revised and Clinical Global
      Impressions-Improvement predefined criteria. RESULTS: There were no statistically
      significant differences in time to first response or first persistent response
      between sertraline and placebo in children, except for time to first response on
      Clinical Global Impressions-Improvement. Sertraline had a significantly faster
      time to first persistent response in adolescents compared to placebo. Within
      treatment groups, children had a significantly faster time to first response than
      adolescents, whether treated with placebo or sertraline, but not on time to first
      persistent response. Both age groups showed similar improvement over 34 weeks of
      treatment. CONCLUSION: In the double-blind studies, children and adolescents had
      different patterns of response with sertraline vs. placebo.

PMID- 17003662
TI  - Cognitive-behavioral therapy for PANDAS-related obsessive-compulsive disorder:
      findings from a preliminary waitlist controlled open trial.
AB  - OBJECTIVE: To provide preliminary estimates of the effectiveness of cognitive
      behavioral therapy (CBT) in treating pediatric obsessive-compulsive disorder
      (OCD) of the pediatric autoimmune neuropsychiatric disorders associated with
      streptococcus (PANDAS) subtype. METHOD: Seven children with OCD of the PANDAS
      subtype (range 9-13 years) were treated in a 3-week intensive CBT program
      conducted at a university clinic. Six of seven children were taking selective
      serotonin reuptake inhibitor medication(s) upon presentation. Assessments were
      conducted at four time points: baseline, pretreatment approximately 4 weeks
      later, posttreatment, and 3-month follow-up. Raters were blind to the nature of
      the study treatment. RESULTS: Six of seven participants were classified as
      treatment responders (much or very much improved) at posttreatment, and three of
      six remained responders at follow-up. Clinician severity ratings, as measured by
      the Children's Yale-Brown Obsessive-Compulsive Scale and Anxiety Disorder
      Interview Schedule for DSM-IV Child Interview Schedule-Parent version, decreased
      significantly following intervention, with effect sizes of 3.38 and 2.29,
      respectively. Self-reported general anxiety and depression symptoms were not
      significantly reduced. CONCLUSIONS: This study provides preliminary support for
      CBT in treating the PANDAS subtype of pediatric OCD. This approach is also
      considered a safe and minimally invasive treatment approach.

PMID- 17003663
TI  - Somatic symptoms in children and adolescents with anxiety disorders.
AB  - OBJECTIVE: To evaluate the prevalence of somatic symptoms (SSs) in children and
      adolescents with anxiety disorders; the relationship between SSs and anxiety
      severity, impairment, and child global functioning; and the impact of fluvoxamine
      (FLV) versus pill placebo (PBO) on reducing SSs. METHOD: As part of a double
      blind, placebo-controlled trial, 128 children (mean age, 10.8 years; range, 6-17)
      with DSM-IV anxiety disorders (i.e., social, separation, and generalized anxiety)
      were assessed by expert clinicians on 16 SSs using the Pediatric Anxiety Rating
      Scale. RESULTS: The most common SSs at baseline were restlessness (74%),
      stomachaches (70%), blushing (51%), palpitations (48%), muscle tension (45%),
      sweating (45%), and trembling/shaking (43%). Older children (age 12 and older)
      reported more SSs than younger children, boys and girls reported similar numbers
      of SSs, and SSs were higher among children with than without generalized anxiety
      disorder. SSs were significantly and positively correlated with anxiety severity,
      impairment, and global functioning. Pre-/postreductions in SSs were statistically
      significant in both PBO and FLV conditions; however, FLV was superior to PBO in
      reducing SSs. CONCLUSIONS: SSs are highly prevalent among children and
      adolescents with anxiety disorders and are associated with greater anxiety
      severity and impairment. Treatment with FLV was effective in reducing rather than
      increasing SSs. The high rates of SSs in youths with each of the three anxiety
      disorders suggest a re-evaluation of SSs in the DSM-IV diagnostic criteria for
      the most common anxiety disorders among children and adolescents.

PMID- 17003664
TI  - Predicting posttraumatic stress symptoms longitudinally in a representative
      sample of hospitalized injured adolescents.
AB  - OBJECTIVE: Adolescents constitute a high-risk population for traumatic physical
      injury, yet few longitudinal investigations have assessed the development of
      posttraumatic stress disorder (PTSD) symptoms over time in representative
      samples. METHOD: Between July 2002 and August 2003, 108 randomly selected injured
      adolescent patients ages 12 to 18 and their parents were interviewed at baseline
      and again 2, 5, and 12 months postinjury. Initially, participants were screened
      for PTSD symptoms with the PTSD Reaction Index (PTSD-RI) and depressive symptoms
      with the Center for Epidemiologic Studies Depression Scale, as well as preinjury
      trauma. Random-coefficient regression was used to assess the association between
      baseline clinical, injury, and demographic characteristics and the development
      and maintenance of PTSD symptoms longitudinally. RESULTS: Between 19% and 32% of
      adolescents screened positive for PTSD (i.e., had PTSD-RI scores of > or =38)
      during the course of the 12 months after the injury. Higher initial adolescent
      PTSD and depressive symptoms, higher emergency department heart rate, greater
      objective event severity, and greater parental preinjury trauma were significant
      independent predictors of higher adolescent PTSD symptoms. CONCLUSIONS: For a
      substantive minority of hospitalized adolescents, high PTSD symptom levels
      persist during the 12 months after injury. Clinical characteristics readily
      identifiable after the acute injury predict the development of PTSD symptoms over
      time. Real-world clinical trials that test screening and intervention procedures
      for representative samples of at-risk youths are warranted.

PMID- 17003665
TI  - Atomoxetine for hyperactivity in autism spectrum disorders: placebo-controlled
      crossover pilot trial.
AB  - OBJECTIVE: To explore placebo-controlled efficacy and safety of atomoxetine (ATX)
      for attention-deficit/hyperactivity disorder (ADHD) symptoms in children with
      autism spectrum disorders (ASD). METHOD: Children ages 5 to 15 with ASD and
      prominent ADHD symptoms were randomly assigned to order in a crossover of
      clinically titrated ATX and placebo, 6 weeks each, separated by 1-week washout.
      Slopes for each condition were compared by paired t test. RESULTS: In 2004-2005,
      12 boys and 4 girls (7 with autistic disorder, 1 Asperger's, 8 pervasive
      developmental disorder not otherwise specified) all completed at least 3 weeks of
      each condition. On the primary outcome, the Hyperactivity subscale of the
      Aberrant Behavior Checklist, ATX was superior to placebo (p =.043, effect size d
      = 0.90). It was also superior on a 0 to 3 rating of nine DSM-IV ADHD
      hyperactive/impulsive symptoms (p =.005, d = 1.27), but missed significance on
      nine inattentive symptoms (p =.053, d= 0.89). Nine subjects responded to ATX,
      four to placebo (25% improvement on the Hyperactivity subscale plus Clinical
      Global Impressions-Improvement of 1-2. One was rehospitalized for recurrent
      violence on ATX. Adverse events were otherwise tolerable, with no tendency to
      stereotypy. CONCLUSIONS: ATX appears safe and effective for treating
      hyperactivity in some children with autism spectrum disorders. The effect appears
      as large as in a multisite methylphenidate trial in the same population, with
      fewer intolerable side effects. Further study in autism spectrum disorders is
      indicated.

PMID- 17003666
TI  - Phenotypic and genetic overlap between autistic traits at the extremes of the
      general population.
AB  - OBJECTIVE: To investigate children selected from a community sample for showing
      extreme autistic-like traits and to assess the degree to which these individual
      traits--social impairments (SIs), communication impairments (CIs), and restricted
      repetitive behaviors and interests (RRBIs)--are caused by genes and environments,
      whether all of them are caused by the same genes and environments, and how often
      they occur together (as required by an autism diagnosis). METHOD: The most
      extreme-scoring 5% were selected from 3,419 8-year-old pairs in the Twins Early
      Development Study assessed on the Childhood Asperger Syndrome Test. Phenotypic
      associations between extreme traits were compared with associations among the
      full-scale scores. Genetic associations between extreme traits were quantified
      using bivariate DeFries-Fulker extremes analysis. RESULTS: Phenotypic
      relationships between extreme SIs, CIs, and RRBIs were modest. There was a degree
      of genetic overlap between them, but also substantial genetic specificity.
      CONCLUSIONS: This first twin study assessing the links between extreme individual
      autistic-like traits (SIs, CIs, and RRBIs) found that all are highly heritable
      but show modest phenotypic and genetic overlap. This finding concurs with that of
      an earlier study from the same cohort that showed that a total autistic symptoms
      score at the extreme showed high heritability and that SIs, CIs, and RRBIs show
      weak links in the general population. This new finding has relevance for both
      clinical models and future molecular genetic studies.

PMID- 17003667
TI  - Serious emotional and behavioral problems and mental health contacts in American
      and British children and adolescents.
AB  - OBJECTIVE: To compare prevalence of serious emotional and behavioral problems and
      mental health contacts for these problems among American and British children and
      adolescents. METHOD: Data on children and adolescents ages 5 to 16 years were
      drawn from the 2004 U.S. National Health Interview Survey (response rate = 79.4%)
      and the 2004 survey of Mental Health of Children and Young People in Great
      Britain (response rate = 76.0%). Emotional problems, hyperactivity/inattention,
      and conduct problems were assessed using the parent version of the Strengths and
      Difficulties Questionnaire (SDQ). Psychometric properties of SDQ scales were
      compared across countries. RESULTS: The SDQ has similar psychometric properties
      across countries. More British than American children met the criteria for
      emotional and conduct problems, but not hyperactivity/inattention. Prevalence was
      higher for all problems in 5- to 8-year-old British boys and for emotional
      problems in 13- to 16-year-old British girls. American children with serious
      emotional and behavioral problems had a higher prevalence of mental health
      contacts overall and with mental health providers but not with general medical
      providers. CONCLUSIONS: British children have a higher prevalence of parent
      reported serious emotional and behavioral problems than American children.
      However, British children with these problems are less likely than American
      children to receive mental health care.

PMID- 17003668
TI  - Self-reports on mental health problems of youth with moderate to borderline
      intellectual disabilities.
AB  - OBJECTIVE: To determine the extent to which the Youth Self-Report (YSR) can be
      used to assess emotional and behavioral problems in adolescents with intellectual
      disabilities (IDs). METHOD: In 2003, 281 11- to 18-year-olds with IDs (IQ > or
      =48) completed the YSR in an interview, and in 1993, 1,047 non-ID adolescents
      completed the YSR themselves. Parents completed the Child Behavior Checklist
      (CBCL). The ID sample was split into lower (IQ 48-69) and higher (IQ > or =70) IQ
      groups. Cronbach's alpha values of the YSR scales and (intraclass) correlation
      coefficients between and within YSR and CBCL scale scores were calculated to
      determine parent-adolescent agreement and YSR construct validity, which were
      compared between samples. Mean YSR scale scores were compared between adolescents
      with ID with and without psychiatric symptoms. RESULTS: Cronbach's alpha, parent
      adolescent agreement, and indications of construct validity were about similar in
      all samples, although discriminant validity was somewhat weaker in the lower IQ
      group. Mean scale scores were 1.5 to 2.0 times higher for ID adolescents with
      psychiatric symptoms. CONCLUSIONS: The YSR seems applicable in youth with an IQ >
      or =48. Further research is needed to refine and confirm these findings and the
      factor structure of the YSR in adolescents with ID and to differentiate between
      adolescents with moderate and mild IDs.

PMID- 17003669
TI  - Help-seeking process of parents for psychopathology in youth with moderate to
      borderline intellectual disabilities.
AB  - OBJECTIVE: To study the help-seeking process of parents for emotional or
      behavioral problems in their child with borderline to moderate intellectual
      disabilities. METHOD: In 2003, in a special education-based sample of 522 youths
      (ages 10-18 years, response = 77.9%), we studied the parents' perception of their
      child's problems, their subsequent felt need for professional help, actual help
      seeking, and the factors possibly related to taking these steps. RESULTS: Even
      when parents indicated their child's emotional or behavioral functioning as
      "neither good nor bad," in about 70%, these problems were present according to
      standardized measures. Of the 213 parents (40.8%) who perceived problems, 70.6%
      felt a need, and 55.2% of these parents subsequently sought professional help.
      Parents more often sought help when their child had problems of anxiety and
      depression, experienced negative life events, and when parents perceived child
      psychopathology before the past year. Reported barriers to seeking help
      predominantly related to parents' evaluation of the severity of these problems
      and wanting to solve the problems themselves. CONCLUSIONS: Clinicians and other
      service providers should address parents' concerns regarding their child's
      emotional/behavioral functioning and treatment seeking. Also, they should provide
      information on treatment options and on signs and potential negative prospects of
      their child's problems.

PMID- 17003670
TI  - Clinical problem solving: the case of John, Part II: excerpts from Sessions 2-7.

PMID- 17003671
TI  - When formulation outweighs diagnosis: 13 "moments" in psychotherapy.

PMID- 17003672
TI  - Use of electronic monitoring induces a 40-day intervention effect in HIV
      patients.

PMID- 17003673
TI  - Group B streptococcus carriers among HIV-1-infected pregnant women according to
      gestational age and regional site of colonization: rate of recovery from various
      sites.

PMID- 17003674
TI  - Concerns about article on code-versus-name reporting of HIV.

PMID- 17003675
TI  - Noninvasive markers of fibrosis in HIV/HCV-coinfected population.

PMID- 17003676
TI  - Men who have sex with men and women: pieces of the U.S. HIV epidemic puzzle.

PMID- 17003677
TI  - A cost-effectiveness evaluation of a jail-based chlamydia screening program for
      men and its impact on their partners in the community.
AB  - BACKGROUND: Few cost-effectiveness evaluations of screening men in jails for
      chlamydia have been published, and none have evaluated the cost-effectiveness of
      providing partner notification services to the partners of chlamydia-infected
      inmates. GOAL: The goal of this study was to evaluate the cost-effectiveness of
      the chlamydia screening and partner notification programs for men conducted by a
      Massachusetts jail compared with 3 hypothetical alternatives. STUDY DESIGN: Using
      jail cost and testing data, we used decision analyses to compare the cost and
      effectiveness of universal screening, age-based screening with 2 age cutoffs, and
      testing of symptomatic inmates at intake using treated cases of chlamydia and
      gonorrhea as the primary outcome. We also evaluated the cost-effectiveness of
      adding partner notification to these alternatives. RESULTS: Universal screening
      was the most effective and expensive alternative. Age-based screening would have
      identified slightly fewer cases at half the cost of universal screening. The net
      cost of partner notification was low. Assuming high sequelae costs in female
      partners made partner notification a cost-saving intervention. CONCLUSIONS: Age
      based screening could lower costs without substantially sacrificing
      effectiveness. Notifying partners of infected inmates was a cost-effective
      adjunct to screening inmates.

PMID- 17003678
TI  - Productivity losses attributable to untreated chlamydial infection and associated
      pelvic inflammatory disease in reproductive-aged women.
AB  - BACKGROUND AND OBJECTIVES: The productivity losses attributable to disease
      related morbidity and mortality impose a burden on society in general and on
      employers in particular. A reliable assessment of the productivity losses
      associated with untreated infection with Chlamydia trachomatis (Ct) would
      complement earlier work on direct medical costs and contribute to an estimate of
      the full cost of chlamydial disease. GOAL: The goal of this study was to estimate
      the discounted lifetime productivity losses attributable to untreated chlamydial
      infection in reproductive-aged women. STUDY DESIGN: We developed a cost model
      using Monte Carlo methods to estimate the lifetime discounted productivity losses
      attributable to untreated lower genital tract Ct infection among reproductive
      aged women. The model considered the impact of disability resulting from acute
      pelvic inflammatory disease (PID) associated with untreated Ct infection and from
      the sequelae of acute PID, including chronic pelvic pain, ectopic pregnancy, and
      infertility. To accommodate disparate Ct infection rates and labor market
      characteristics across age groups, we matched age-based risk factors for Ct
      infection with labor market patterns. Data sources included the 2001 National
      Chlamydia Surveillance Data, the 2001 Current Population Survey, and published
      literature. RESULTS: Estimates indicate that the mean weighted productivity
      losses per untreated Ct infection were approximately US dollars 130 (in year 2001
      dollars). Mean weighted productivity losses per case of acute PID were estimated
      at US dollars 649. Estimated productivity losses were highly correlated with age,
      reflecting age-dependent differences in labor market characteristics.
      CONCLUSIONS: The productivity losses attributable to untreated infection with Ct
      and to sequelae of this infection form a substantial portion of the total
      economic burden of disease. Effective programs to prevent chlamydial infection
      and effective screening, diagnosis, and treatment of Ct-infected women may reduce
      productivity losses and substantially lessen the economic burden of disease to
      employers.

PMID- 17003679
TI  - Antiretroviral therapy and HIV prevention in India: modeling costs and
      consequences of policy options.
AB  - OBJECTIVES: The objective of this study is to assess the costs, cost
      effectiveness, and HIV epidemic impact of 3 antiretroviral therapy (ART) policy
      options. STUDY DESIGN: We constructed an epidemiologic model to predict the
      course of the HIV epidemic in the absence of expanded ART availability. Based on
      background studies of the willingness to pay for ART among patients with AIDS, of
      the costs to the government of the alternative treatment interventions, and of
      ART's likely effects on HIV transmission, we simulated the consequences of 3
      possible alternative government ART policies. RESULTS: A program to reduce the
      negative consequences of the currently unstructured private-sector provision of
      ART is the most cost-effective of the 3 options at a 10% discount rate and least
      cost-effective at a 3% rate. The costs and cost-effectiveness of all options are
      highly sensitive to the effect of ART on condom use. CONCLUSION: The design of
      ART policy should capitalize on the potential of ART to decrease HIV transmission
      through institutional arrangements that reward effective prevention programs,
      thereby raising the likelihood that treatment has beneficial rather than negative
      external effects.

PMID- 17003680
TI  - The costs of treating curable sexually transmitted infections in low- and middle
      income countries: a systematic review.
AB  - BACKGROUND: Calls for increased investment in sexually transmitted infection
      (STI) treatment across the developing world have been made to address the high
      disease burden and the association with HIV transmission. GOALS: The goals of
      this study were to systematically review evidence on the cost of treating curable
      STIs and to explore its key determinants. STUDY: A search of published literature
      was conducted in PubMed and supplemented by reviews of gray literature. Studies
      were analyzed by broad focus. Regression analysis explored how intervention
      characteristics affect unit costs, accounting for differences in costing methods.
      RESULTS: Fifty-three primary studies were identified, of which 62% used empirical
      data, 35% presented economic costs, and 22% presented full costs. The median STI
      treatment cost was US dollars 17.80. Clinics serving symptomatic patients were
      consistently cheaper than outreach services, services using syndromic management
      protocols had lower costs, and unit costs decreased with scale. CONCLUSIONS: The
      compiled cost data provide an evidence base that can be used to help inform
      resource planning.

PMID- 17003682
TI  - The direct medical cost of epididymitis and orchitis: evidence from a study of
      insurance claims.
AB  - BACKGROUND: Epididymitis and orchitis (EO) are the primary sequelae of acute
      chlamydia and gonorrhea in men. Existing estimates of the cost per episode of
      epididymitis are over 10 years old or are based on limited data. OBJECTIVE: The
      objective of this study was to estimate direct medical costs of EO from insurance
      claims data. STUDY DESIGN: We used 1998 and 1999 insurance claims taken from a
      national database. We used International Classification of Diseases, 9th Revision
      codes to identify inpatient and outpatient claims for EO treatment. Prescription
      drug claims were identified with National Drug Codes. To capture episodes of EO
      that were most likely sequelae of sexually transmitted diseases, we categorized
      claims based on age at the time of the initial EO claim. RESULTS: The total cost
      per episode was US dollars 368 for males <13 years of age, US dollars 242 for
      those > or =13 and <41 years of age, and US dollars 291 for those > or =41 years
      of age. The cost for both younger and older men was significantly different from
      men > or =13 and <41 years of age. Inpatient claims were relatively rare,
      occurring in < or =1.2% of total episodes. CONCLUSION: The cost per episode we
      calculated was lower than previously published estimates and can be attributed to
      a lower rate of inpatient care than previously observed or estimated.

PMID- 17003684
TI  - Prolonged recruitment efforts in health surveys: effects on response, costs, and
      potential bias.
AB  - BACKGROUND: In health surveys, considerable effort and expense are invested to
      achieve a high response proportion and thereby to reduce selection bias. We
      investigated the interrelation of recruitment efforts and expense with potential
      nonresponse bias based on data from a large health survey. METHODS: In a
      population-based health survey, a stratified sample of 6640 residents of the
      Augsburg (Germany) region was selected, of whom 4261 attended the main study
      between October 1999 and April 2001. A short telephone interview yielded
      additional information on nearly half of the nonparticipants. All recruitment
      contacts were documented, and expenses were estimated on the basis of unit costs.
      Different recruitment strategies were modeled retrospectively. We compared their
      cost savings as well as their influence on the response proportion and on
      prevalence estimates. RESULTS: The distribution of total contacting cost per
      individual was highly skewed with 50% of the total sum spent on 17% of the
      sample. Late responders showed many similarities with nonresponders; both
      included a higher percentage of people with impaired health and with greater
      behavioral health risks. We were able to identify recruitment strategies that may
      save up to 25% of the recruitment costs without significant shift in the
      parameter estimates. Data collected in the short nonresponder interview proved to
      be important to correct for possible nonresponse bias. CONCLUSIONS: In general,
      prolonged recruitment efforts lead to a larger and more representative sample but
      at increasing marginal costs. Specific cost-saving recruitment strategies that do
      not enhance response bias can be suggested. Interviews of nonresponders are also
      useful.

PMID- 17003683
TI  - Maternal DDT exposures in relation to fetal and 5-year growth.
AB  - BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) is an organochlorine pesticide
      still used in areas of the world where malaria vector control is needed. Few
      studies have examined in utero exposures to DDT in relation to fetal and early
      childhood growth in populations with substantial exposure to DDT. Furthermore,
      only a portion of these studies have investigated in utero exposures and growth
      during childhood. METHODS: To assess the role of in utero exposures to DDT on
      fetal and early childhood growth, we analyzed data from mothers and children who
      participated in the Child Health and Development Study (CHDS), a cohort study of
      20,754 women and their pregnancies conducted in the San Francisco Bay area during
      the 1960s. We measured p,p'-DDE, o,p'-DDT, and p,p'-DDT concentrations from the
      stored sera of 399 women collected during pregnancy. Outcomes were measured at
      the child's birth and at 5 years of age. RESULTS: Maternal p,p'-DDE
      concentrations were considerable in this study, averaging 6.9 micrograms per gram
      lipid. After covariate adjustment, a small increase in gestational age was
      observed with increases in p,p'-DDT and o,p'-DDT, but there was no association
      with p,p'-DDE. At 5 years of age, an increase from the 25th to the 75th
      percentile in p,p'-DDE was related to a 2-mm increase in head circumference (95%
      confidence interval = 0 to 4). Overall effect sizes were small and imprecise.
      Furthermore, there was little evidence of specificity for a given outcome or
      exposure at either age. CONCLUSIONS: At the concentrations studied in this
      sample, DDT compounds did not appear to impair fetal or 5-year growth.

PMID- 17003685
TI  - Genetic and environmental correlates of semen quality: a twin study.
AB  - BACKGROUND: The influences of environmental factors on the male reproductive
      system have been much debated over the last 3 decades. We studied the impact of
      genes and environment on semen quality, sex hormone levels, and sperm chromatin
      stability by using a twin design. METHODS: The study population consisted of
      monozygotic and dizygotic twins from the population-based Danish Twin Registry
      and a random selection of pairs of singleton brothers from the Danish Civil
      Registration System. All men were 20 to 45 years of age. The study population
      comprised 100 monozygotic twin brothers (50 pairs), 102 dizygotic twins (51
      pairs), and 102 single-born brothers (51 pairs). A semen sample and blood sample
      were collected from all participants. RESULTS: Heritability was estimated to
      account for 20% (95% confidence interval = 0% to 68%) of the variation in sperm
      density. A higher heritability was found for the hormones reflecting Sertoli cell
      function (inhibin B, 76% [36% to 84%] and follicle-stimulating hormone, 81% [40%
      to 88%]) and for percent morphologic normal cells (41% [0% to 60%] and sperm
      chromatin parameters (mean alphaT, 68% [34% to 81%] and COMP alphaT, 72% [25% to
      82%], respectively). CONCLUSION: Our study indicates a substantial hereditary
      component in plasma levels of hormones reflecting Sertoli cell function and in
      sperm cell chromatin stability and morphology. The environmental contribution
      (including the prenatal environment) appeared to be largest for sperm count.

PMID- 17003686
TI  - Impact of high temperatures on mortality: is there an added heat wave effect?
AB  - BACKGROUND: Mortality during sustained periods of hot weather is generally
      regarded as being in excess of what would be predicted from smooth temperature
      mortality gradients estimated using standard time-series regression models.
      However, the evidence for an effect of continuous days of exceptional heat ("heat
      wave effect") is indirect. In addition, because some interventions may be
      triggered only during forecasted heat waves, it would be helpful to know what
      fraction of all heat-related deaths falls during these specific periods and what
      fraction occurs throughout the remainder of the summer. METHODS: Extended time
      series data sets of daily mortality counts in 3 major European cities (London, 28
      years of data; Budapest, 31 years; Milan, 18 years) were examined in relation to
      hot weather using a generalized estimating equations approach. We modeled
      temperature and specific heat wave terms using a variety of specifications.
      RESULTS: With a linear effect of same-day temperature above an identified
      threshold, an additional "heat wave" effect of 5.5% was observed in London (95%
      confidence interval = 2.2 to 8.9), 9.3% in Budapest (5.8 to 13.0), and 15.2% in
      Milan (5.7 to 22.5). Heat wave effects were reduced slightly when we relaxed the
      linear assumption and these effects were reduced substantially when temperature
      was modeled as an average value of lags 0 to 2 days. In London, fewer than half
      of all heat-related deaths could be attributed to identified heat wave periods.
      In Milan and Budapest, the fraction was less than one fifth. CONCLUSIONS: Heat
      wave effects were apparent in simple time-series models but were reduced in
      multilag nonlinear models and small when compared with the overall summertime
      mortality burden of heat. Reduction of the overall heat burden requires
      preventive measures in addition to those that target warnings and responses
      uniquely to heat waves.

PMID- 17003687
TI  - Risk factors for childhood diarrhea incidence: dynamic analysis of a longitudinal
      study.
AB  - BACKGROUND: Several longitudinal studies have investigated factors associated
      with childhood diarrhea in developing countries. However, most studies have
      neglected important dynamic features of the longitudinal design and hierarchical
      interrelationships among the potential risk factors. METHODS: We conducted a
      longitudinal study of 902 children, age 0 to 36 months at baseline, in a large
      urban center in northeastern Brazil. Diarrhea data were collected by following
      children from October 2000 until January 2002 with biweekly home visits. We used
      a dynamic time-to-event analysis to account for several longitudinal features. We
      applied an effect-decomposition strategy to quantify direct and indirect effects
      of risk factors grouped in different blocks. RESULTS: Child's age and an
      autoregressive effect of past diarrhea episodes explained some of the decline of
      diarrhea incidence observed throughout the study (from more than 14 episodes to 2
      episodes per child-year), a phenomenon already observed but not explained in
      other longitudinal diarrhea studies. We identified the following major diarrhea
      determinants: low socioeconomic status, poor sanitation conditions, presence of
      intestinal parasites, and absence of prenatal examination. The effect of
      socioeconomic status was mediated mostly by living and sanitation conditions.
      CONCLUSION: Our study shows important advantages of applying a dynamic analysis
      approach to longitudinal observational studies of diarrhea or other acute
      diseases and highlights the complex interrelationships of diarrhea determinants.
      Our results confirm the importance of sanitation as a major determinant of child
      health in urban settings of developing countries.

PMID- 17003688
TI  - Altered semen quality in relation to urinary concentrations of phthalate
      monoester and oxidative metabolites.
AB  - BACKGROUND: Phthalates are multifunctional chemicals used in a variety of
      consumer, medical, and personal care products. Previously, we reported dose
      response associations of decreased semen quality with urinary concentrations of
      monobutyl phthalate (MBP) and monobenzyl (MBzP) phthalate, which are metabolites
      of dibutyl phthalate and butylbenzyl phthalate, respectively. The present study
      extends our work in a larger sample of men and includes measurements of di(2
      ethylhexyl) phthalate (DEHP) oxidative metabolites. METHODS: Between January 2000
      and May 2004, we recruited 463 male partners of subfertile couples who presented
      for semen analysis to the Massachusetts General Hospital. Semen parameters were
      dichotomized based on World Health Organization reference values for sperm
      concentration (<20 million/mL) and motility (<50% motile) and the Tygerberg
      Kruger Strict criteria for morphology (<4% normal). The comparison group was men
      with all 3 semen parameters above the reference values. In a single spot urine
      sample from each man, phthalate metabolites were measured using solid-phase
      extraction coupled to high-performance liquid chromatography isotope-dilution
      tandem mass spectrometry. RESULTS: There were dose-response relationships of MBP
      with low sperm concentration (odds ratio per quartile adjusted for age,
      abstinence time, and smoking status = 1.00, 3.1, 2.5, 3.3; P for trend = 0.04)
      and motility (1.0, 1.5, 1.5, 1.8; P for trend = 0.04). There was suggestive
      evidence of an association between the highest MBzP quartile and low sperm
      concentration (1.00, 1.1, 1.1, 1.9; P for trend = 0.13). There were no
      relationships of monoethyl phthalate, monomethyl phthalate, and the DEHP
      metabolites with these semen parameters. CONCLUSION: The present study confirms
      previous results on the relationship of altered semen quality with exposure to
      MBP at general population levels. We did not find associations between semen
      parameters and 3 DEHP metabolites.

PMID- 17003689
TI  - Stability of nevirapine suspension in prefilled oral syringes used for reduction
      of mother-to-child HIV transmission.
AB  - OBJECTIVE: To reduce mother-to-child transmission (MTCT) of HIV, we assessed the
      stability of nevirapine suspension in an oral dosing syringe over a range of
      storage conditions. DESIGN: A mother-to-child transmission dosing kit, containing
      a maternal nevirapine tablet and infant nevirapine suspension in an oral syringe
      that can be dispensed to the pregnant woman to use at delivery. However, the
      manufacturer only packages nevirapine in 240 mL, multidose containers and there
      are no published stability data for nevirapine suspension repackaged in an oral
      syringe. METHODS: Nevirapine suspension 6 mg/0.6 mL in 3 mL amber BAXA Exacta-Med
      Oral Dispensers (Baxa Corporation, Englewood, CO) were stored under the following
      conditions: 26 degrees C/high relative humidity (RH), 40 degrees C/low RH, 40
      degrees C/high RH, refrigerated and frozen -30 degrees C for 6 months. The
      samples were assayed monthly for nevirapine by HPLC-UV. At 3, 4, and 6 months the
      samples were cultured for pathogens. RESULTS: : There were no significant
      decreases in nevirapine concentrations in the prefilled syringes compared with
      baseline. Nevirapine became more concentrated in syringes incubated at 40 degrees
      C/low RH due to evaporation resulting in the suspension becoming more viscous. No
      pathogens were cultured. CONCLUSIONS: Nevirapine suspension is stable and
      pathogen free at varying conditions for 6 months in Baxa Exacta-Med Oral
      Dispensers.

PMID- 17003690
TI  - Aberrant induction of regulatory activity of CD4+CD25+ T cells by dendritic cells
      in HIV-infected persons with amebic liver abscess.
AB  - To know why HIV-1-infected persons are particularly susceptible to amebic liver
      abscess (ALA), we investigated the role of CD4CD25 T cells in the susceptibility
      of HIV-1-infected persons to this disease. Herein we show, in early stage HIV-1
      infected subjects, that CD4 T-cell responses to Entamoeba histolytica antigen
      (EhAg) were selectively impaired, especially in those with ALA. EhAg-specific CD4
      T-cell responses were normalized by depletion of CD4CD25 cells or by addition of
      anti-cytotoxic T lymphocyte antigen 4 (CTLA4) antibody. Regulatory activity of
      CD4CD25 T cells to suppress the EhAg-specific CD4 T-cell response could be
      induced by EhAg-primed dendritic cells (DCs) in HIV-1-infected subjects,
      especially in those with ALA, but not in healthy controls. Exogenous Tat
      incubated DCs derived from HIV-negative subjects also could upregulate CTLA4
      expression on autologous CD4CD25 T cells and selectively suppress the EhAg
      specific CD4 T-cell response. The results imply an interaction of the two
      pathogens: HIV-1, perhaps through the effect of Tat on DCs, may upregulate EhAg
      specific regulatory T-cell activity to suppress T-cell response to E.
      histolytica, thus increasing the susceptibility to invasive amebiasis in even
      early-stage HIV-1-infected persons.

PMID- 17003691
TI  - Simple Pediatric AIDS Severity Score (PASS): a pediatric severity score for
      resource-limited settings.
AB  - BACKGROUND: A multidimensional pediatric AIDS severity score (PASS) has been
      developed for severity adjustment and as a predictive model for mortality in a
      pediatric HIV-infected population. While the prognostic value of PASS is relevant
      in the US setting, there is a need to develop a simpler model of PASS for use in
      resource-limited settings where CD4% values and HIV RNA levels may not be
      available to assess prognosis and guide treatment decisions. METHODS: A Simple
      PASS model was developed including baseline weight percentile, WHO stage,
      symptoms, a general health rating, total lymphocyte count, packed-cell volume,
      and albumin measures from 1178 perinatally HIV-infected children enrolled into a
      prospective cohort study (PACTG 219). This prognostic model was then validated
      among 952 perinatally HIV-infected children enrolled in other PACTG research
      studies at the same sites. Survival estimates and Hazard Ratios (HR) were
      obtained using the Kaplan-Meier method and proportional hazards models,
      respectively. The predictive ability of the models was determined using Harrell's
      "C" statistic. RESULTS: Of the clinical measures and assays considered in this
      study, weight percentile, WHO stage, symptomatology, general health rating, total
      lymphocyte count, packed-cell volume, and albumin were found to be predictive of
      mortality. The simple PASS model including only the simple clinical measures and
      assays was found to be predictive of mortality (C statistic = 0.852). Its
      discriminative ability for mortality was comparable to a model consisting of the
      Simple PASS plus CD4% (C statistic = 0.871). CONCLUSION: The Simple PASS scoring
      system provides a reasonable alternative to CD4% values and HIV viral-load levels
      to assess prognosis and guide decisions about antiretroviral therapy initiation
      in resource-limited settings.

PMID- 17003692
TI  - The Pediatric AIDS Severity Score (PASS): a multidimensional AIDS-severity
      adjustment for pediatric HIV infection.
AB  - BACKGROUND: A severity staging system predictive of mortality for perinatally HIV
      infected children is needed for clinical and research purposes. METHODS: A
      pediatric AIDS severity score (PASS) was developed using baseline
      sociodemographic, clinical, immunologic, and functional measures obtained from
      786 perinatally HIV-infected children enrolled into a prospective cohort study
      (PACTG 219) in the pre-highly active antiretroviral therapy (HAART) era (pre
      1996). PASS was then validated among 392 perinatally HIV-infected children
      randomly sampled from the original source population (n = 1178). Survival
      estimates and hazard ratios (HRs) were obtained using the Kaplan-Meier method and
      proportional hazards models, respectively. The most predictive models were
      determined using Harrell's "C" statistic. RESULTS: Overall survival was 95% and
      90% at 1 and 2 years of follow-up, respectively. The most comprehensive model for
      predicting mortality, termed the "Full" PASS, included CD4% <15 (HR = 3.9), CDC
      category C (HR = 2.6), BMI <10% (HR = 2.4), a low (<70) neuropsychological score
      (HR = 2.6), a general health rating <5 (HR = 2.4), and an elevated symptoms score
      (HR = 1.9). These determinants were highly predictive of mortality (C statistic =
      0.841). CONCLUSIONS: PASS will be helpful in assessing the effectiveness of ART
      among children with HIV infection, particularly when randomized clinical trials
      are not possible due to ethical and feasibility concerns.

PMID- 17003693
TI  - Demographic and behavioral contextual risk groups among men who have sex with men
      participating in a phase 3 HIV vaccine efficacy trial: implications for HIV
      prevention and behavioral/biomedical intervention trials.
AB  - Recent outbreaks of syphilis and gonorrhea coupled with reported increases in HIV
      risk behavior among men who have sex with men (MSM) have raised concerns about a
      potential resurgence of HIV among MSM. These concerns have led some to suggest
      the need for a paradigm shift in how HIV-prevention programs are designed and
      implemented. In this analysis, baseline demographic, sexual partnership, and
      substance use information was used to identify contextual-risk groups among 5,095
      HIV-seronegative MSM enrolled in a 36-month phase 3 HIV vaccine efficacy trial
      across 61 sites primarily in North America. Eight demographic and behavioral
      contextual risk groups were identified, with annualized HIV seroincidence ranging
      from 1.8% to 6.3% across groups. Men in primary HIV-serodiscordant relationships
      had the lowest HIV seroincidence (1.8%), while an older group of men with many
      sex partners had the highest (6.3%). Visit-schedule compliance and study
      retention were lowest among younger non-White men and highest among older popper
      users, with annualized HIV seroincidence of 2.9% and 3.5%, respectively.
      Differences in HIV incidence, study compliance, and retention observed among
      contextual-risk groups suggest that responsiveness to heterogeneity within risk
      group (eg, MSM) could benefit screening, enrollment, and retention of HIV
      prevention programs and intervention trials, reducing the time and cost related
      to their design, implementation, and conclusion.

PMID- 17003694
TI  - Reconciling different infectivity estimates for HIV-1.
AB  - In our article, "HIV-1 Epidemics Driven by Late Stage Disease," we conclude that
      the probability of transmission of HIV through promiscuous or casual sexual
      contacts is significantly higher in the third or symptomatic stage of the
      disease. Our results differ greatly from those of the current literature. The
      primary stage or first stage has been reported to be the most infectious based on
      an article by Jacquez et al. More recently, the Wawer et al study of monogamous
      heterosexual couples in Rakai, Uganda found that the transmission of HIV was most
      likely to occur in the first 5 months after infection. We describe how the
      findings of the Wawer et al study might be compatible with our results. We also
      respond to a response by Koopman and Simon, who seem to criticize their own paper
      severely and choose not to defend it against our remarks.

PMID- 17003695
TI  - Natural pregnancies in HIV-serodiscordant couples receiving successful
      antiretroviral therapy.
AB  - Increasing numbers of HIV-serodiscordant heterosexual couples are concerned about
      the chances for pregnancy. We reviewed all natural pregnancies attained by HIV
      serodiscordant couples seen in 3 clinics in Spain, in which the infected partner
      had undetectable plasma viremia while receiving highly active antiretroviral
      therapy (HAART). In the case of HIV-infected mothers, only those with
      undetectable viremia during pregnancy and at delivery were chosen. A total of 62
      HIV-serodiscordant couples, 22 HIV-infected women (mean CD4 count of 522
      cells/microL, 55% hepatitis C virus [HCV]-seropositive) and 40 HIV-infected men
      (mean CD4 count of 629 cells/microL, 75% HCV-seropositive), were recorded.
      Overall, 76 natural pregnancies occurred, and 68 children were born. There were 9
      fetal deaths, 1 twin pregnancy, 6 couples with 2 consecutive babies, and 4
      couples with 3 consecutive newborns. There were no cases of HIV seroconversion in
      uninfected sexual partners. One case of vertical HIV transmission occurred,
      however. Serodiscordant couples attaining natural pregnancy are exposed to a
      negligible risk of sexual transmission of HIV when the infected partner presents
      with complete suppression of plasma viremia while receiving HAART.

PMID- 17003696
TI  - Objective pulsatile tinnitus: a video clip demonstration of the condition.
AB  - Pulsatile tinnitus is an uncommon condition. We describe a case of pulsatile
      tinnitus and visually demonstrate a pulsating tympanic membrane caused by a
      postoperative cerebrospinal leak into the mastoid air cells following resection
      of a left temporal petrous meningioma. To our knowledge, this is the first case
      in the literature where an objective pulsatile tinnitus has been captured on
      video (see www.laryngoscope.com).

PMID- 17003697
TI  - Endoscopic-assisted reduction of anterior table frontal sinus fractures.

PMID- 17003698
TI  - Image guided transoral approach to the pterygopalatine fossa.
AB  - OBJECTIVES: We present a transoral approach using image guidance to approach
      inferiorly based lesions of the pterygopalatine fossa. STUDY DESIGN: Case report.
      METHODS: A 49-year-old male presenting with a benign cyst of the inferior
      pterygopalatine fossa. The presentation, workup, and management are discussed.
      RESULTS: The patient underwent a computed tomography scan that confirmed the
      location of the lesion in the left pterygopalatine fossa. An image guidance
      system was used to effect a complete transoral resection of the benign cyst.
      CONCLUSIONS: Benign lesions of the pterygopalatine fossa may be successfully
      accessed using a transoral approach with image guidance, which minimizes
      postoperative morbidity.

PMID- 17003700
TI  - Treatment of squamous cell carcinoma of the retromolar trigone.

PMID- 17003701
TI  - The community management of chylous fistula using a pancreatic lipase inhibitor
      (orlistat).
AB  - We describe two innovative ideas in the treatment of iatrogenic chyle leak. The
      first is the early use of a pancreatic lipase inhibitor (Orlistat) to reduce fat
      absorption and chyle production, with consequent faster fistula healing. The
      second is the treatment of these patients at home in the community by district
      nurses backed by the hospital staff. This domiciliary approach has a positive
      psychological effect on the patient, permits the patient to take responsibility
      for their treatment, and reduces hospital length of stay minimising patient
      exposure to nosocomial infections.

PMID- 17003702
TI  - Subtotal laryngectomy with tracheohyoidopexy: a possible alternative to total
      laryngectomy.
AB  - OBJECTIVE: The objective of this study was to describe a new subtotal
      laryngectomy technique that foresees two variations: 1) tracheohyoidopexy (THIP +
      A or A-A)-subtotal removal of the larynx maintaining one or two cricoarytenoid
      units and subsequent tracheohyoidopexy; and 2) tracheohyoidoepiglottopexy (THIEP
      + A or A-A)-resection guarantees preservation of the suprahyoid epiglottis
      maintaining one or two cricoarytenoid units and further suspension of the
      tracheal stump at the epiglottis and hyoid bone. METHODS: The technique is
      described, step by step, extending laryngeal resection beyond the limits adopted
      for supracricoid subtotal laryngectomy (SSL). Unlike SSL, tracheohyoidopexy
      allows glottic tumors with subglottic extension (T2-T3) to be treated, not only
      laryngeal tumors with invasion of one cricoarytenoid joint (T3), but also locally
      advanced laryngeal tumors with anterior extension through the thyroid cartilage
      (T4). RESULTS: A total of 30 operations have been performed: 22 THIEP and eight
      THIP. In one case, total laryngectomy was necessary 16 days postoperatively as a
      result of a large pharyngostoma. One month after the operation, all patients were
      able to tolerate a soft diet. Tracheostomy was removed within 43 postoperative
      days only in 26 cases. Phonatory results are comparable to those obtained with
      supracricoid laryngectomy. No definite oncologic conclusions can be drawn, at
      present, as a result of the short follow-up period. CONCLUSIONS:
      Tracheohyoidopexy is a supracricoid laryngectomy extended toward the cricoid,
      which, like total laryngectomy, focuses on radical resection of T and N.
      Functional results are similar to those obtained with SSL; it is mandatory to
      maintain one functioning cricoarytenoid unit and a wide pyriform sinus.

PMID- 17003703
TI  - Application of magnetic resonance virtual endoscopy as a presurgical procedure
      before sialoendoscopy.
AB  - OBJECTIVES: The objectives of this study were to investigate the feasibility of
      clinical application of magnetic resonance (MR) virtual endoscopy as a
      presurgical procedure before sialoendoscopy and to evaluate its value in the
      diagnosis of obstructive salivary gland diseases and preoperative visualization
      of endoluminal views. STUDY DESIGN: This study presents our initial experience to
      use MR virtual endoscopy for the presurgical visualization of salivary duct lumen
      and ductal pathologies in comparison to the sialoendoscopy findings in a
      feasibility study. METHODS: Six consecutive patients with suspected obstructive
      salivary gland diseases underwent MR sialography with a three-dimensional fast
      imaging using steady-state acquisition. The three-dimensional MR data were
      transferred to an independent workstation and were postprocessed with navigator
      software to generate three-dimensional reconstruction and virtual endoscopic
      images. The fly-through mode was used to imitate the sialoendoscopic exploratory
      procedure. Then the patients underwent sialoendoscopy and the endoscopic findings
      were compared with the preoperative virtual endoscopic images. RESULTS: The MR
      data acquisition and postprocessing protocol were feasible. The virtual endoscopy
      created clear endoluminal views of salivary duct and the ductal pathologies. The
      diagnoses were all confirmed by surgical sialoendoscopy. The virtual endoscopic
      images showed close resemblance to the sialoendoscopic findings. CONCLUSIONS: MR
      virtual endoscopy is an effective and noninvasive diagnostic method for
      evaluating the endoluminal anatomy and pathologies of the salivary duct. The
      clinical application of MR virtual endoscopy as a presurgical procedure before
      sialoendoscopy is a valuable and promising approach, which can provide surgeons
      useful morphologic and pathologic information.

PMID- 17003704
TI  - Response of the female vocal quality and resonance in professional voice users
      taking oral contraceptive pills: a multiparameter approach.
AB  - OBJECTIVE/HYPOTHESIS: The purpose of this study was to analyze the vocal quality
      and resonance (nasality and nasalance values) during the menstrual cycle in
      professional voice users using oral contraceptive pills (OCPs). Although
      professional voice users are more sensitive and aware of their vocal quality, no
      changes of voice and resonance characteristics were expected because OCPs create
      a stable hormonal balance throughout the menstrual cycle. STUDY DESIGN: The
      authors conducted a comparative study of 24 healthy, young professional voice
      users using OCPs. One assessment was performed between the 10th and 17th day of
      pill intake, when hormonal levels reached a steady state. The second assessment
      was performed during the first 3 days of menses, when no pills were taken and
      hormonal levels were minimized. METHODS: Subjective (perceptual evaluation of
      voice and nasality) and objective (aerodynamic, voice range, acoustic, Dysphonia
      Severity Index [DSI], nasometer) assessment techniques were used. RESULTS: : The
      Mann-Whitney U test showed no significant difference between the perceptual
      evaluation of the voice and the nasality in the two assessments. The paired
      Student t test showed no significant difference regarding the maximum phonation
      time, the vocal performance, the acoustic parameters, and the DSI. CONCLUSIONS:
      These findings indicate that OCPs do not have an impact on the objective and
      subjective voice and resonance parameters in young professional voice users. This
      information is specifically relevant to professional voice users who are more
      aware of vocal quality changes and ear, nose and throat specialists/voice
      therapists who treat professional voice users with voice problems/disorders.
      Further research regarding the impact of increased vocal load during the
      premenstrual or menstrual phase in professional voice users using OCPs should be
      considered.

PMID- 17003705
TI  - Management of the radial forearm free flap donor site with the vacuum-assisted
      closure (VAC) system.
AB  - INTRODUCTION: The radial forearm free flap is a popular reconstructive flap in
      modern head and neck surgery. Poor wound healing at the forearm donor site is
      common and frequently results in tendon exposure. The Vacuum-Assisted Closure
      (VAC) system (Kinetic Concepts Inc., San Antonio, TX) is a topical negative
      pressure dressing that has been shown to improve skin graft viability when used
      as a bolster dressing. In this study, we investigated the use of the VAC system
      in the management of the radial forearm free flap donor site. METHODS: A
      retrospective chart review was performed on all subjects who underwent a radial
      forearm free flap reconstruction in which the VAC system was used as a bolster
      dressing at the donor site from January 1, 2003, through March 31, 2005. RESULTS:
      Thirty-four consecutive subjects were included in the study. Exposed tendon did
      not occur in 14 (0%) subjects in which the VAC bolster was used for a minimum of
      6 days. Eleven of the 20 subjects (55%) who used the VAC bolster for 5 days
      demonstrated small amounts of tendon exposure (<2 cm) on follow-up clinic
      examination. The minimum follow up for all subjects was 4 months. CONCLUSION:
      This study demonstrates that the VAC system is a feasible alternative to
      conventional bolster dressing in the management of the radial forearm free flap
      skin-grafted donor site. Based on this study, when used for a minimum of 6 days,
      the VAC bolster dressing eliminated tendon exposure at the forearm donor site.

PMID- 17003706
TI  - The efficacy of mitomycin-C in the treatment of laryngotracheal stenosis.
AB  - OBJECTIVE: The purpose of this study is to evaluate whether the addition of
      topical mitomycin-C (MMC) application to the wound site after endoscopic
      treatment of laryngotracheal stenosis (LTS) resulted in measurable improvement in
      clinical outcomes. STUDY DESIGN AND SETTING: A retrospective chart review of
      patients with LTS treated by the senior author over a 6-year period was
      performed. The treatment groups were stratified into two main categories: 1)
      endoscopic treatment alone and 2) endoscopic treatment + topical MMC. The
      "symptom-free" interval was determined (in months) for each subject using a two
      tailed t test for statistical analysis of the control/study groups. RESULTS:
      Sixty-seven procedures were performed in 36 patients with LTS with a mean of 1.86
      surgical treatments per patient. The mean duration of the symptom-free interval
      after endoscopic treatment for LTS was 4.9 months in the endoscopic-only
      treatment group and 23.2 months in the endoscopic group receiving topical MMC.
      The symptom-free interval observed in the MMC group was significantly longer than
      the control subjects (P = 1 x 10). CONCLUSIONS: The results of this study suggest
      that MMC is an effective adjuvant in the treatment of LTS. The results of this
      study provide strong supporting evidence that topical MMC is an effective
      adjuvant in the treatment of LTS.

PMID- 17003707
TI  - Radiofrequency tongue reduction through a cervical approach: a pilot study.
AB  - OBJECTIVE/HYPOTHESIS: The objective of this prospective cohort study was to
      determine the feasibility, safety, and efficacy of radiofrequency tongue base
      reduction through a cervical approach in patients with obstructive sleep apnea
      syndrome (OSAS). METHODS: Patients with moderate to severe OSAS and predominant
      tongue base obstruction by physical examination were included at our institution
      from 1999 to 2003. A sonogram was obtained to identify the lingual arteries, and
      an electrode was inserted through the neck and into the tongue under fluoroscopic
      guidance. Adverse events were recorded as well as efficacy on snoring (visual
      analog scale), daytime sleepiness (Epworth score), and polysomnography. RESULTS:
      The 10 patients received a mean of 14,288 +/- 3,251 J per session. No cases of
      tongue palsy or infection occurred. During the first 7 days, mean pain score (0
      10 scale) was 1.3 +/- 1.5. Snoring volume (0-10 scale) decreased from 6.2 +/- 2.3
      to 3.9 +/- 2.6 (P = .017) and sleepiness (0-24 scale) from 8.7 +/- 5.6 to 4.7 +/-
      3.3 (P = .011). The respiratory disturbance index (events/hour) decreased from
      52.0 +/- 19.6 to 33.6 +/- 24.4 (P = .016). Mean minimal oxygen saturation (%)
      increased from 64.2 +/- 13.0 to 75.8 +/- 10.3 (P = .003). Sleep architecture
      improved although not significantly. CONCLUSION: Radiofrequency tongue base
      reduction through a cervical approach proved feasible and safe despite the large
      energy doses used. Fluoroscopic guidance enables to place the electrode at the
      desired site of treatment. Although OSAS improved in nine of 10 patients, greater
      efficacy might be achieved in patients with less severe OSAS at baseline. Studies
      are needed to correlate objective clinical efficacy with the dose per lesion site
      and the number of lesion sites per session.

PMID- 17003708
TI  - A novel reconstructive technique after endoscopic expanded endonasal approaches:
      vascular pedicle nasoseptal flap.
AB  - BACKGROUND: In patients with large dural defects of the anterior and ventral
      skull base after endonasal skull base surgery, there is a significant risk of a
      postoperative cerebrospinal fluid leak after reconstruction. Reconstruction with
      vascularized tissue is desirable to facilitate rapid healing, especially in
      irradiated patients. METHODS: We developed a neurovascular pedicled flap of the
      nasal septum mucoperiosteum and mucoperichondrium based on the nasoseptal artery,
      a branch of the posterior septal artery (Hadad-Bassagasteguy flap [HBF]). A
      retrospective review of patients undergoing endonasal skull base surgery at the
      University of Rosario, Argentina, and the University of Pittsburgh Medical Center
      was performed to identify patients who were reconstructed with a vascularized
      septal mucosal flap. RESULTS: Forty-three patients undergoing endonasal cranial
      base surgery were repaired with the septal mucosal flap. Two patients with
      postoperative cerebrospinal fluid leaks (5%) were successfully treated with focal
      fat grafts. We encountered no infectious or wound complications in this series of
      patients. One patient experienced a posterior nose bleed from the posterior nasal
      artery. This was controlled with electrocautery and the flap blood supply was
      preserved. CONCLUSION: The HBF is a versatile and reliable reconstructive
      technique for defects of the anterior, middle, clival, and parasellar skull base.
      Its use has resulted in a sharp decrease in the incidence of postoperative
      cerebrospinal fluid leaks after endonasal skull base surgery and is recommended
      for the reconstruction of large dural defects and when postoperative radiation
      therapy is anticipated.

PMID- 17003709
TI  - Contour and paired-point registration in a model for image-guided surgery.
AB  - OBJECTIVES/HYPOTHESIS: This study assesses target registration error (TRE) of
      contour-based registration (CBR) and paired-point registration (PPR) for
      endoscopic sinus surgery. STUDY DESIGN: The experimental registration model
      consisted of a replica of a human head (Sawbones #1345-27; Pacific Research
      Laboratories, Vashon, WA). Twelve surface fiducial markers were affixed to the
      simulated skin on the model, and titanium screws were placed in the regions of
      the anterior ethmoid (AE) and sphenoid face (SF). An axial computed tomography
      scan (1-mm slice thickness) was then obtained. METHODS: Registration was then
      performed on the InstaTrak 3500 Plus (GE Surgical Navigation & Visualization,
      Lawrence, MA) with the standard PPR protocol with 12 points and CBR protocol with
      500, 250, 125, 50, and 4 points. TRE was then calculated at the AE and SF
      targets. RESULTS: Target registration error was significantly lower for paired
      point registration compared with contour-based registration (AE, 0.5 mm vs. 1.5
      mm, P < .0001; SF, 0.8 mm vs. 1.5 mm, P < .0001). Among contour-based
      registration protocols, target registration error at the sphenoid face was lowest
      with 50 points (1.5 mm, P < .02). At the anterior ethmoid, contour-based
      registration with 50 points produced a lower target registration error than
      contour-based registration with 125 points (1.5 vs. 1.8 mm, P < .01). Other
      target registration error values for CBR were similar at both regions. The target
      registration error interquartile range was lowest with CBR-125 at both regions.
      CONCLUSIONS: Paired-point registration provided significantly lower target
      registration error. Contour-based registration with 125 points (and possibly as
      few as 50 points) produces clinically acceptable target registration error. This
      registration model elucidates important concepts about registration for surgical
      navigation for sinus surgery.

PMID- 17003710
TI  - Sensorineural hearing loss in Vogt-Koyanagi-Harada syndrome.
AB  - BACKGROUND: Vogt-Koyanagi-Harada (VKH) syndrome is a systemic condition
      characterized by ocular inflammatory disease as well as skin, ear, and meningeal
      manifestations. Patients with VKH often report tinnitus and hearing loss, but
      these symptoms tend to be given secondary consideration because most undergo
      treatment with steroids to prevent blindness resulting from granulomatous
      uveitis, exudative retinal detachment, and optic nerve inflammation.
      METHODS/STUDY DESIGN: In the current retrospective review, 24 patients with this
      syndrome were screened for auditory system abnormalities. All patients denied
      history of noise exposure or ototoxic agent exposure. The age range of the
      patients was 13 to 42 years. RESULTS: Three patients reported tinnitus and two
      patients reported sudden hearing loss. One patient experienced vertigo and aural
      fullness. Eight of 24 patients had pure-tone thresholds greater than 25 dB
      hearing loss at two or more frequencies. Five of 24 of these patients experienced
      hearing loss outside of the 95% confidence interval for published age-matched
      control populations. There was sloping sensorineural hearing loss at 4 kHz and
      above in five of 24 patients. All eight patients with hearing loss experienced
      some degree of hearing loss at 4 kHz or above. Three patients had mild to
      moderate low-frequency sensorineural hearing loss. There were no tympanometric
      abnormalities suggestive of conductive involvement. Abnormal acoustic reflex
      decay was observed in one patient. CONCLUSIONS: We conclude that a significant
      number of patients with VKH experience sensorineural hearing loss and that every
      patient with VKH should undergo a review of systems for auditory abnormalities
      and referral for audiologic testing if symptomatic. It is possible that untreated
      patients may experience worse symptoms.

PMID- 17003711
TI  - Neck management in patients undergoing postradiotherapy salvage laryngeal surgery
      for recurrent/persistent laryngeal cancer.
AB  - OBJECTIVE: To determine a plan for the management of cervical lymph nodes in
      patients undergoing salvage laryngeal surgery (SLS) for recurrent/persistent
      laryngeal cancer after primary radiotherapy (RT). STUDY DESIGN: : Retrospective
      chart review. METHODS: Charts of 51 consecutive patients who had salvage total or
      supracricoid laryngectomy with or without neck dissection for
      recurrent/persistent laryngeal squamous cell carcinoma after primary RT from 1988
      to 2005 in our institution were reviewed. No patients received concomitant or neo
      adjuvant chemotherapy. Thirty-four patients underwent SLS along with unilateral
      or bilateral neck dissection, whereas 17 patients underwent the SLS without neck
      dissection. Reports of preRT and preSLS staging of the primary tumor and the
      neck, recorded using the TNM system, were reviewed. Reports of the final
      histopathologic examination for the excised laryngeal cancer and cervical lymph
      nodes were reviewed. RESULTS: Thirty-four patients underwent SLS with unilateral
      or bilateral neck dissection. The preRT staging of the primary tumor for those 34
      patients showed that 32 (94%) were staged T-1 (14) and T-2 (18), whereas the
      preSLS staging of the primary tumor for those 34 patients showed that 29 (85%)
      were staged T-3 and T-4. The postSLS final histopathologic examination of the
      excised lymph nodes in those 34 patients demonstrated that 30 (88%) did not have
      any evidence of nodal metastasis. On comparing patients with and without nodal
      metastasis (on their postSLS final histopathology), we found that the preSLS neck
      staging, based on computed tomographic (CT) scanning of the neck, was
      significantly associated with the negative/positive postSLS status of nodal
      metastasis (P = .006). Of 29 patients staged preSLS as N-0, 28 (97%) patients did
      not have nodal metastasis on their postSLS final pathology (negative predictive
      value = 97%, confidence interval, 82.2-99.9). PreRT neck staging, preRT and
      preSLS staging of the primary tumor, along with laryngeal subsite involvement
      (supraglottis, glottis, subglottis) did not significantly correlate with the
      status of neck metastasis on final postSLS histopathology (P = .68, 0.78, 0.49,
      and 0.42, respectively). None of the 34 patients had any neck tumor recurrence in
      the postSLS follow-up period (median, 3 yr). In addition, all 17 patients who
      underwent SLS without neck dissection were staged N-0 both before RT as well as
      preSLS, and none developed neck disease in the postSLS follow-up period (median,
      2.5 yr). CONCLUSION: Management of the neck in patients undergoing salvage total
      or supracricoid laryngectomy for laryngeal cancer recurrence/persistence after
      primary RT should be based on the preSLS CT staging of the neck. Patients staged
      N-0 preSLS are not likely to harbor occult nodal metastasis and therefore may not
      require elective neck dissection.

PMID- 17003712
TI  - Clinical significance of results from olfactory testing.
AB  - BACKGROUND: Although widely used in healthy subjects and patients with olfactory
      loss, the significance of changes of scores from validated olfactory tests is
      unknown. AIM AND METHODS: The aim of the present study was to relate the self
      assigned changes of olfactory function in terms of "better," "unchanged," and
      "worse" in patients with smell disorders with the results from olfactory testing
      by means of a validated test set. Olfactory function of 83 anosmic or hyposmic
      patients (40 women, 43 men; age 12-84 yr) was tested on two occasions (mean
      interval 136 days, minimum 7 days, maximum 6.7 yr). Olfactory function was
      assessed using a validated technique ("Sniffin' Sticks"). This test consists of
      three subtests, one for odor threshold (T), odor discrimination (D), and odor
      identification (I), with possible results ranging up to 16 points each. From the
      sum of the results from the three subtests a composite "TDI" score was obtained.
      RESULTS: Forty-four patients indicated an improvement of olfactory function,
      whereas 39 patients reported no change. No subject reported deterioration of
      olfactory sensitivity. Subjects assigned to group BETTER had higher TDI scores in
      the second olfactory tests than subjects assigned to the group UNCHANGED, both in
      absolute terms and as compared with the first olfactory test (effect "test
      occasion" by "self-assessed improvement," P < .001). There was no significant
      difference between groups with respect to age and sex (P = .99 and .84,
      respectively). Logistic regression showed that more than 60% of the subjects
      reported an improvement of olfactory sensitivity when the TDI score increased by
      5.5 points. CONCLUSION: We show that there is a statistically significant
      relation between measured and perceived improvement of olfactory function in
      patients who first presented with the diagnosis of anosmia or hyposmia. The
      results indicate that improved olfactory function in patients with olfactory
      deficiency is perceived as such in everyday life and is quantitatively related to
      an improvement in the composite TDI score of the "Sniffin' Sticks" olfactory test
      battery. This is the basis for the application of a specific therapy for
      olfactory loss because of a possible gain in quality of life for the patients.

PMID- 17003713
TI  - Pediatric tonsillotomy with radiofrequency technique: long-term follow-up.
AB  - OBJECTIVES: Compare the effects of partial tonsil resection using a
      radiofrequency technique, tonsillotomy (TT), with total tonsillectomy (TE, blunt
      dissection) after 1 and 3 years. Compare frequency of relapse in snoring or
      infections and possible long-term changes in behavior among TT children with
      those in TE children. METHOD: Ninety-two children (5-15 yr) randomized to TT (n =
      49) or TE (n = 43) groups because of obstructive problems with or without
      recurrent tonsillitis. One year after surgery, general health, degree of
      obstruction, history of infections, and behavior were investigated using two
      questionnaires, the Qu1 and Child Behavior Checklist, as well as an ENT visit.
      After 3 years, two questionnaires, Qu2 and the Glasgow Children's Benefit
      Inventory, were answered by mail. RESULTS: : After 1 year, both groups were in
      good health. The effect on snoring and total behavior was the same for both
      groups, and the rate of recurrence of infections was not higher in the TT group.
      After 3 years, two children in the TT group were tonsillectomized (4%, 2/49), one
      because of peritonsillitis and another because of increased snoring. Otherwise,
      no differences existed between the groups in general health, snoring, or number
      of infections. CONCLUSION: Removing only the protruding parts of the tonsils has
      the same beneficial long-term effect on obstructive symptoms and recurrent throat
      infections as complete TE in the majority of cases. The need for re-operation is
      low; therefore, it appears inadvisable to follow the current common practice of
      routinely removing the whole tonsil given its higher morbidity and risk for
      serious complications.

PMID- 17003714
TI  - Age-dependent degeneration of the stria vascularis in human cochleae.
AB  - OBJECTIVE: Aging is a common cause of acquired hearing impairments. This study
      investigated age-related morphologic changes in human cochleae, with a particular
      focus on degeneration of the stria vascularis (SV) and the spiral ganglion (SG).
      STUDY DESIGN: Retrospective case review. METHODS: The study group comprised 91
      temporal bones from individuals aged 10 to 85 years who had no history or
      audiometric findings suggestive of specific causes of cochlear degeneration. We
      quantified the SV and SG atrophy at each cochlear turn using morphometric
      measurements. Correlations of the SV and SG atrophy with age, audiometric
      patterns of hearing loss, and auditory thresholds were statistically
      investigated. RESULT: The SV and the SG both showed a tendency for progressive
      atrophy to develop with age. However, statistically significant correlations were
      observed between aging and SV atrophy only in the apical and basal cochlear
      turns. These findings were consistent with those reported previously in gerbils.
      No significant correlations were detected between SV or SG atrophy and
      audiometric findings. CONCLUSION: SV atrophy appears to be the most prominent
      anatomic characteristic of aged human cochleae.

PMID- 17003715
TI  - Chemopreventive effect of celecoxib in oral precancers and cancers.
AB  - OBJECTIVES: Oral cancer has become an important health care problem in many
      countries. Because this disease develops slowly, early detection and intervention
      can greatly affect ultimate outcome. Celecoxib is a cyclooxygenase-2 inhibitor
      with significantly less toxicity. This study investigated the possibility of
      using it for chemoprevention of oral cancer at the early stages. STUDY DESIGN:
      Randomized animal study. METHODS: Dysplastic lesions were induced in the buccal
      pouches of 47 hamsters by a 5 week painting of 9,10-dimethl-1,2-benzanthrancene
      (DMBA). Basal diets or diets containing 500 or 1,500 ppm of Celecoxib were orally
      given for 7 weeks. The T50 (50% incidence; i.e., the time to appearance of tumors
      in 50% of the hamsters) was observed, and volume of tumors was measured on day 1,
      9, 19, 28, 35, and 48 with the Celecoxib treatment. RESULTS: The T50 was 9, 19,
      and 28 days with the treatment in the control group, in the 500 ppm group, and in
      the 1,500 ppm group, respectively. It indicated that the Celecoxib treatment
      could delay progression of early lesion. The tumor measurement showed that this
      treatment was also effective in delaying tumor growth in both treatment groups.
      There was a difference in the treatment efficacy between the 500 ppm and 1,500
      ppm of Celecoxib, indicating a dose-dependent efficacy. CONCLUSIONS: Celecoxib is
      effective in delaying onset of early lesions induced by DMBA and in slowing
      growth of the tumors in hamster cheek pouches during the postinitiation stage.
      Its treatment efficacy appears to be dose dependent.

PMID- 17003716
TI  - Analysis of the long-term hearing results after the surgical repair of aural
      atresia.
AB  - OBJECTIVES: Careful surgical candidate selection guarantees a high probability of
      serviceable hearing postoperatively in congenital aural atresia (CAA) patients.
      The authors analyzed hearing results after CAA surgery with long-term follow-up
      (F/U) with respect to several clinical factors. STUDY DESIGN: This was a
      retrospective study. METHODS: The medical records of 93 CAA patients (100 ears)
      who underwent operations from January 1987 through December 2002 at Seoul
      National University Hospital were reviewed. Mean duration was 56.9 months. The
      authors evaluated the results of hearing after surgery over 3 year F/U with a
      view to clarifying the factors accounting for unsuccessful results. RESULTS:
      Approximately 64% of patients treated surgically achieved a considerable hearing
      gain over long-term F/U. Postoperative hearing remained relatively stable over
      the period from 6 months to 3 years postoperatively, yielding only 2.75 dB of
      aggravation. However, hearing results in revision cases deteriorated with time,
      which led to statistically higher air-conduction thresholds than those of primary
      cases at the 1 and 3 year F/Us. Resultantly, only 26.6% of patients having
      achieved a poor hearing gain post first surgery benefited from revision
      audiologically. The severity of microtia was found to help predict poor long-term
      hearing outcomes after CAA surgery. CONCLUSIONS: Nonrevision cases and cases with
      mild microtia appear to have acceptable and stable long-term hearing results.
      Disappointing long-term hearing results in revision, and severe microtia cases
      should lead to considerations of alternative options in these cases, such as bone
      anchored hearing aids, which offer reliable and stable results.

PMID- 17003717
TI  - Useful landmarks in arytenoid adduction and laryngeal reinnervation surgery.
AB  - OBJECTIVE: Knowledge of the location of the muscular process of the arytenoid
      cartilage and the recurrent laryngeal nerve is essential to performing a
      successful arytenoid adduction and laryngeal reinnervation surgery. We describe
      external landmarks useful in locating these structures. STUDY DESIGN: Cadaveric
      laryngeal dissection. METHODS: Posterior laryngeal dissection was performed in 16
      human larynges. The position of the muscular process of the arytenoid was
      measured bilaterally relative to the inferior and superior borders of the thyroid
      lamina. The recurrent laryngeal nerve was followed distally from slightly below
      the level of the cricothyroid joint to its genu where its vertical course changes
      to an oblique intralaryngeal course. RESULTS: The muscular process of the
      arytenoid was usually found halfway between the roots of the superior and
      inferior cornu of the thyroid lamina. The recurrent laryngeal nerve was found
      just deep to the cricothyroid joint and lateral to the posterior cricoarytenoid
      muscle. There were no other nerves in this area. CONCLUSIONS: This study finds
      that the superior and inferior borders of the thyroid lamina are useful
      intraoperative landmarks to locate the muscular process of the arytenoid. The
      cricothyroid joint provides a good starting point to locate the recurrent
      laryngeal nerve, which can be identified slightly deeper between it and the
      posterior cricoarytenoid muscle.

PMID- 17003718
TI  - Endoscopic techniques in resection of anterior skull base/paranasal sinus
      malignancies.
AB  - OBJECTIVE: The objective of this study was to examine the role of endoscopic
      approaches to the resection of anterior skull base and paranasal sinus
      malignancies at one tertiary care medical center. STUDY DESIGN: The authors
      conducted a retrospective chart review over a period of 17 years. METHODS:
      Patients undergoing anterior skull base resections for malignancies over a 17
      year period were reviewed. Data were collected on each patient with respect to
      the pathology of the tumor and approach used as well as demographic and follow-up
      information. RESULTS: A total of 78 patients were treated at a tertiary care
      medical center for malignancies of the paranasal sinuses and anterior skull base.
      The most common diagnosis was squamous cell carcinoma occurring in 33% of the
      cases. The remaining pathologies included esthesioneuroblastoma (23%), adenoid
      cystic carcinoma (15%), melanoma (3%), sinonasal undifferentiated carcinoma (3%),
      lymphoma (5%), nasopharyngeal carcinoma (4%), and other tumor types (14%).
      Endoscopic techniques were used extensively in this population of patients.
      Combined approaches using a sublabial/transmaxillary approach and coronal
      approaches were used when indicated and complemented the endoscopic approach. A
      majority of patients were without evidence of disease at the end of this review.
      Using endoscopic techniques allowed for acceptable cosmetic results and facial
      incisions were used minimally. CONCLUSION: With complete endoscopic surgical
      resection followed by radiation therapy, local recurrence, morbidity, and
      cosmetic deformity have been minimized. The microscopic view provided by
      endoscopic techniques, with or without complementary approaches, allows for
      complete tumor removal.

PMID- 17003719
TI  - A new generation videokymography for routine clinical vocal fold examination.
AB  - OBJECTIVE: This study aims to introduce a new-generation videokymographic system,
      which provides simultaneous laryngoscopic and kymographic image, for routine
      clinical vocal fold examination. STUDY DESIGN: The authors explored a new imaging
      method for diagnosis and evaluation of voice disorders. METHODS: The new
      generation videokymographic system includes two charge-coupled device image
      sensors, a color area image sensor, and a monochromic high-speed line-scan image
      sensor. The high-speed line-scan image sensor is used to capture the kymogram,
      and the color area image sensor is used to obtain the laryngoscopic image. The
      two images can be displayed simultaneously on a video monitor or stored in a
      standard video recorder. Three subjects with nonpathologic voice were
      investigated in detail with the new videokymographic system. RESULTS: The high
      quality laryngoscopic image and kymogram can be used directly for clinical
      purposes with no further postprocessing. The scan position of the kymogram is
      always indicated in the laryngoscopic image, which provides feedback for the
      operator to easily locate the expected scanning position. All varieties of vocal
      fold vibration, including irregular vibrations, phonation onset and offset, can
      be observed with the presented method. The continuous kymogram of the vocal fold
      vibration can be retrieved from a kymographic image sequence for quantitative
      analysis. CONCLUSIONS: The new-generation videokymography provides a simple,
      quick means to investigate vocal fold vibration, especially for voice disorders.
      It can emerge as an important tool for routine clinical vocal fold examination.

PMID- 17003720
TI  - Histomorphometric estimation of air cell development in experimental otitis
      media.
AB  - OBJECTIVES: The objectives of this study were to examine the effect of acute
      otitis media on the bony development of the growing middle ear air cell system
      with a reliable and concise stereologic histomorphometric method and to generate
      a standard baseline growth plot for the middle ear of the rat. STUDY DESIGN: The
      authors conducted a histomorphometric analysis of bullar volume during the entire
      growth period after early induction of unilateral otitis media. METHODS: The
      authors conducted undecalcified processing of 27 rat skulls sectioned
      horizontally at various ages from 20 to 83 days after unilateral transtympanic
      injection of Streptococcus pneumoniae at 19 days postpartum. Stereologic
      estimation of bullar volume was performed in the experimental and the control ear
      with Cavalieri's principle. Body mass and air cell volume were plotted as
      functions of subject age using standard developmental equations on the
      experimental results. RESULTS: Volumes of the middle ear air cell system were
      consistently smaller in the otitis ears. Bullar growth was completed at 60 days
      regardless of otitis history, but body mass was increasing throughout the
      experimental period. CONCLUSIONS: A single incident of otitis media introduced
      early in life is sufficient to significantly reduce the final volume of the bulla
      in rats. This finding may mimic the effect of otitis media contracted in early
      childhood on the development of the mastoid air cells. The standard growth plot
      provides a timeframe for studies of signaling molecules responsible for bone
      modeling in pneumatization.

PMID- 17003721
TI  - Clinical implementation of endoscopic thyroidectomy in selected patients.
AB  - OBJECTIVES: Systematic investigation of minimal access thyroid compartment
      surgery combined with the advent of several key new technologies has culminated
      in the implementation of endoscopic thyroidectomy in specific clinical
      situations. STUDY DESIGN: : The authors conducted a prospective, nonrandomized
      analysis of a consecutive cohort of surgical patients from the Medical College of
      Georgia Thyroid Center. METHODS AND MATERIALS: A series of patients meeting
      specific criteria underwent thyroid surgery with the intention of performing
      endoscopic thyroidectomy. Demographic and clinical data were prospectively
      collected and included age, gender, indications for surgery, length of incision,
      need for conversion, and pathology. RESULTS: Thirty-five patients successfully
      underwent 36 endoscopic thyroidectomies between February 2005 and March 2006
      (representing 28.8% of the 125 thyroidectomies done during that period of time).
      There were 32 females and three males with a mean age of 45.3 +/- 13.9 years.
      There were five total thyroidectomies and 31 hemithyroidectomies. The mean
      incision length was 24.2 +/- 0.5 mm. There were no cases of permanent
      hypocalcemia or recurrent laryngeal nerve paralysis. Factors that increased the
      difficulty of endoscopic surgery included obesity, the presence of thyroiditis,
      and nodules >2.5 cm. CONCLUSIONS: The combination of new technology and careful
      experimental investigation has spawned a new era of thyroidectomy in which
      definitive management of thyroid pathology may be accomplished through an
      incision of <1 inch. This approach is feasible in the hands of surgeons with high
      volume thyroidectomy practices who are comfortable with endoscopic principles.
      The cosmetic advantages are self-evident.

PMID- 17003722
TI  - Clinical evaluation of Parkinson's-related dysphonia.
AB  - OBJECTIVES: Nearly one third of patients with idiopathic Parkinson's disease
      (IPD) cite dysphonia, characterized subjectively as causing a harsh and breathy
      voice, as their most debilitating deficit. Medical or behavioral treatments may
      lead to voice improvement. The purpose of this study was 1) to determine whether
      vocal fold injection of Cymetra (micronized form of collagen, elastin,
      proteoglycans; Lifecell Co.) is associated with changes in dysphonic voice
      characteristics in subjects with IPD, as judged perceptually using a standard
      instrument Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V), and (2)
      which acoustic and aerodynamic measurements of voice are most reflective of any
      observed perceptual changes in voice. STUDY DESIGN: Prospective clinical
      evaluation of patients with Parkinson's-related dysphonia (PRD). METHODS: Six
      patients with PRD were evaluated before treatment for the presence of dysphonia
      and glottal gap. All subjects underwent transoral vocal fold collagen injection
      using topical anesthesia in the otolaryngology clinic as part of their clinical
      care. At the initial clinic visit, and 10 to14 days after vocal fold collagen
      injection, patients were asked to complete the Voice Handicap Index (VHI), a
      questionnaire concerning voice-related quality of life, and perceptual analyses
      of voice quality were performed. In addition, patients underwent acoustic
      (pitch/loudness range, maximum phonation time [MPT], and aerodynamic phonation
      threshold pressure [PTP]) voice analysis. RESULTS: Five of six subjects had self
      perceived improvements in voice after treatment, as determined by the VHI (range,
      +8 to -24). All five subjects who completed testing demonstrated decreased PTP
      (range, -1.3 to -2.7, P = .002). Five of six subjects demonstrated statistically
      significant improvements in MPT (range, -2-16 s, P = .05). Five of six subjects
      had improved pitch range (-26-343 Hz), whereas all subjects had increased
      intensity range (0.6-23 db) after injection. CONCLUSIONS: Transoral collagen
      injection in patients with PRD is safe, well tolerated, and is an effective
      temporary method of subjectively improving voice and speech in selected patients
      with IPD. Reduction of glottal gap with collagen improves MPT and subglottal PTP.
      The resulting gain of vocal efficiency may reduce vocal fatigue and provide a
      useful adjunct to voice therapy for PRD.

PMID- 17003723
TI  - Delayed extrusion of hydroxyapatite after transpetrosal reconstruction.
AB  - OBJECTIVES: : To review the long-term results of hydroxyapatite closure of
      transpetrosal defects. STUDY DESIGN: : Retrospective chart review. METHODS: : One
      hundred seventy-seven patients were followed for more than 5 years. After
      surgical management by way of transpetrosal routes, hydroxyapatite was placed
      after medial wound closure with abdominal fat and before a three-layered lateral
      soft tissue closure. RESULTS: : Among this group of patients, three (1.7%)
      cerebrospinal fluid (CSF) leaks were encountered. None of these required re
      operation. Delayed extrusion of hydroxyapatite with concomitant superficial wound
      infections have occurred in seven (4%) patients. All required operative re
      intervention. CONCLUSIONS: : Hydroxyapatite has proven to be an effective
      material in the closure of skull base defects. Nevertheless, delayed extrusion of
      this agent can occur, resulting in the potential for morbidity and the need for
      operative re-intervention.

PMID- 17003724
TI  - Butterfly cartilage graft inlay tympanoplasty for large perforations.
AB  - OBJECTIVE: Butterfly graft inlay tympanoplasty is a well-established technique
      for the repair of small perforations. However, the efficacy of the technique for
      medium and large tympanic membrane perforations remains unknown. STUDY DESIGN:
      Retrospective case series. METHODS: Postauricular tympanoplasty and
      tympanomastoidectomy using a large butterfly cartilage inlay graft (>4 mm
      diameter to total drum replacement) were analyzed in 90 pediatric patients (99
      ears). RESULTS: Patient ages ranged from 2 to 20 years; mean follow-up duration
      was 27.6 months. Successful closure occurred in 92% of the ears. No graft
      lateralized nor displaced into the middle ear. No retraction pocket occurred
      during the follow-up period. In 62 cases, intact canal wall or canal wall window
      tympanomastoidectomy was performed; Fifty-one (82.2%) of the patients having
      mastoidectomy procedures had chronic otitis media with cholesteatoma. The mean
      preoperative to postoperative four-tone air-bone gap improved from 23 to 21 dB;
      the number of patients with 0 to 10 dB hearing results increased from 16 ears
      preoperatively to 32 ears postoperatively. Postoperative suboptimal results
      included eight patients with postoperative perforations in the residual tympanic
      membrane adjacent to an intact cartilage graft; two of these patients were the
      only individuals who exhibited otorrhea. CONCLUSIONS: Cartilage butterfly graft
      inlay tympanoplasty is effective in the vast majority of patients with moderate
      to large perforations. The closure rate exceeded 90% with no graft displacement,
      postoperative adverse events were respectably low, and hearing results improved
      or remained stable despite the need for concurrent mastoidectomy in the majority
      of patients.

PMID- 17003725
TI  - Surgical treatment of chronic recurrent rhinosinusitis: a preliminary report.
AB  - OBJECTIVE: The objective of this study was to determine if endoscopic sinus
      surgery (ESS) is effective in the management of chronic recurrent rhinosinusitis
      (CRRS). METHODS: A consecutive series of patients with CRRS diagnosed according
      to stringent criteria was prospectively examined before and at least 1 year after
      ESS. Paranasal sinus computed tomography scans were staged and ESS was performed
      targeting radiographic disease and the ostiomeatal complex. Preoperative and
      postoperative disease severities in terms of symptom scores, medicine
      utilization, and resource factors were assessed using the rhinosinusitis symptom
      inventory (RSI). Improvements in RSI symptom domains, medical and economic
      resource factors were determined using effect sizes and statistical comparison
      before and after ESS. RESULTS: Nineteen patients (mean age, 42.3 years) completed
      the study with a mean follow up of 19.1 months. The mean Lund score was 3.42
      (standard deviation, 4.09). Statistically significant decreases in nasal (-36.1),
      facial (-28.4), oropharyngeal (-34.6), systemic (-24.7), and total (-31.9) RSI
      symptom domain scores were observed (all P < .003) with effect sizes ranging from
      0.87 to 1.63 (strong surgical effect). Statistically significant decreases in
      antihistamine use (-30%, P = .031), number of workdays missed as a result of CRRS
      (-1.9, P = .035), and number of acute infectious episodes (-2.5, P = .006) were
      also observed. However, declines in weeks of antibiotic use (-2.8 weeks, P =
      .293) and number of antibiotic courses (-1.7, P = .118) were not significant.
      CONCLUSIONS: Patients with CRRS may substantially benefit both symptomatically
      and medically from ESS. Although surgery should be used cautiously in treating
      CRRS, further trials of ESS for CRRS are warranted.

PMID- 17003726
TI  - Topical pimecrolimus 1% for the treatment of pruritic external auditory canals.
AB  - OBJECTIVES/HYPOTHESIS: To understand the role and efficacy of topical
      pimecrolimus in the treatment of refractory pruritus of the external auditory
      canals (EACs). STUDY DESIGN: Retrospective chart review. METHODS: Thirty-six
      patients with pruritic EACs who had failed conventional therapy with topical and
      systemic medications were treated with topical pimecrolimus 1% for a period of 3
      months. Baseline and follow-up evaluation of the degree of pruritus among other
      variables was performed. A control group of 19 patients was instructed on aural
      toilet alone and was not treated with topical pimecrolimus 1%. RESULTS: Of the 36
      patients who were treated with topical pimecrolimus for their pruritic EACs, 34
      patients had resolution of their symptoms. There was evidence of return of
      cerumen production in 86% of patients. In the control group, 16% of patients had
      improvement of their symptoms with aural toilet. This difference was
      statistically significant (chi, P < .0001). CONCLUSIONS: Topical pimecrolimus
      appears to be more efficacious than aural toilet in the treatment of pruritic
      ears for chronic use without side effects.

PMID- 17003727
TI  - Office steroid injections of the larynx.
AB  - OBJECTIVE: Steroid injection into the larynx has been sporadically reported as
      helpful in benign lesions of the larynx. Its role in laryngology remains unclear.
      This study reviews the indications and results of 47 steroid injections in 34
      patients in an office setting. METHODS: The authors conducted a retrospective
      review of 47 injections in 34 patients. Methylprednisolone acetate suspension,
      USP (40 mg/mL), was injected by indirect laryngoscopy under local anesthesia.
      Results were evaluated by stroboscopy and by perceptual evaluation of the GRABS
      scale before and after injection. Pre- versus postinjection ratings were compared
      by paired t test. RESULTS: Indications for injection were: 1) postoperative scar
      with local stiffness (12 patients), 2) vocal nodules and polyp (18 patients), and
      3) sarcoidosis/granuloma (4 patients). Steroid injections were done in
      professional singers instead of repeated oral administration of steroids and/or
      to avoid surgery in patients with polyps and cysts. Improvement was noted in 28
      of 34 (82%). Eleven of the 18 patients with polyps and nodules had significant
      improvement and avoided surgery. Vocal fold scars improved after injection with
      an improved voice grade (P < .01), an improved amplitude (P < .05), and improved
      mucosal wave (P < .05). There were no complications. Only two patients could not
      tolerate office injection. CONCLUSION: Office steroid injections are a valuable
      adjunct in management of vocal fold scars, polyps, nodules, and granulomas.

PMID- 17003728
TI  - Cartilage regeneration in the rabbit nasal septum.
AB  - OBJECTIVE: Rhinoplasty frequently includes harvesting of nasal septal cartilage.
      The objective of this prospective basic investigation is to determine whether
      cartilage can regenerate after submucosal resection (SMR) of the nasal septum in
      the rabbit. Neocartilage formation has not heretofore been described in this
      model. METHODS: By lateral rhinotomy, SMR was performed on 17 rabbits followed by
      reapproximation of the perichondrium. After 7 months, septi were fixed,
      sectioned, and examined histologically. Findings were photographed and data
      tabulated according to location and extent. RESULTS: Sites of matrix-secreting
      isogenous chondrocyte islands were identified between the perichondrial flaps of
      every animal, principally in the anterior inferior septum. The width of the
      islands averaged 190 microm, and the mean neocartilage height was found to be 840
      microm. The newly formed cartilage consisted of chondrocytes within chondrons and
      was comparable in shape and structure to native septal cartilage. CONCLUSIONS:
      After SMR, rabbit cartilage tissue can regenerate and form matrix within the
      potential space created by surgery. The surrounding stem cell-rich perichondrium
      may be the site of origin for these chondrocytes. These findings suggest that
      after SMR of the human nasal septum, it may be possible for new cartilage tissue
      to develop provided the mucosa is well approximated. This biologic effect may be
      enhanced by insertion of cytokine-rich tissue scaffolds that exploit the native
      ability of septal perichondrium to regenerate and repair cartilage tissue.

PMID- 17003729
TI  - Quality of life of patients with otitis media and caregivers: a multicenter
      study.
AB  - OBJECTIVE: The objective of this study was to determine the quality of life of
      otitis media (OM) patients and their caregivers. STUDY DESIGN: A cross-sectional
      study was conducted at 11 otolaryngology and five pediatric clinics in the United
      States between July 1998 and August 1999. All patients, regardless of primary
      complaint, completed a demographic survey, OM-6 survey, and Child Health
      Questionaire-PF28 survey by proxy. Physicians completed an International
      Classification of Diseases, 9th Revision diagnosis sheet for each patient.
      METHODS: Analysis, including Spearman rank correlation, was restricted to study
      patients with active OM. RESULTS: A total of 1,001 patients with active OM were
      identified: 503 OM with effusion, 267 acute OM, and 258 recurrent acute OM.
      Median patient age was 2 years (interquartile range, 1-5). Mean caretaker age was
      32.6 years (standard deviation, 7.4). There was moderate correlation between OM
      frequency and physical suffering (r = 0.50; P < .001) and caregiver concerns (r =
      0.45; P < .001). Moderate correlation was found between percentage of time with
      fluid in the ears and caregiver concerns (r = 0.46; P < .001) and physical
      suffering (r = 0.43; P < .001). OM patients over 5 years of age scored
      significantly worse than healthy children ages 5 to 7 years in almost all areas
      of global health, including physical functioning and impact on caretaker's
      personal time and emotions. CONCLUSION: The global quality of life of patients
      with OM over 5 years of age is worse than that of healthy children of similar
      age. Physical suffering and caregiver concerns are associated with frequent OM or
      effusion duration. Hopefully, these results will direct the focus of future
      outcomes studies.

PMID- 17003730
TI  - Fluorescent retrograde axonal tracing of the facial nerve.
AB  - OBJECTIVE: The objective of this study was to investigate retrograde fluorescent
      axonal labeling of motor nerves as an aid to surgical dissection in
      otolaryngology-head and neck surgery. METHODS: Cholera toxin B subunit conjugated
      to a fluorescent dye was injected into the facial musculature of New Zealand
      white rabbits. At variable time points after injection, the facial nerves were
      harvested and analyzed for fluorescence in the peripheral axon. RESULTS: All
      injected animals demonstrated axonal fluorescence. No animal demonstrated facial
      weakness. Fluorescence was detected a maximum of 20 mm from the distal end of the
      nerve. Time periods greater than 48 hours did not substantially increase
      transport distance. CONCLUSIONS: Cholera toxin B subunit fluorescent conjugates,
      when administered intramuscularly, reliably label the distal portion of the
      facial nerve. In vivo labeling of a motor nerve may have significant potential
      for identifying a nerve in surgery. This work represents a preliminary
      investigation into the adaptation of in vivo fluorescence techniques as an aid to
      surgical dissection. Further research to refine this technique should be
      supported.

PMID- 17003731
TI  - Incidence and characteristics of facial nerve stimulation in children with
      cochlear implants.
AB  - OBJECTIVES: Electrical stimulation from a cochlear implant can spread beyond the
      auditory nerve. The aims of this study were to accurately measure facial nerve
      stimulation in pediatric implant users and to determine the characteristics and
      incidence of this unwanted activity. Part A consisted of a prospective study of a
      randomized sample of 44 pediatric implant users. Part B consisted of a
      retrospective analysis of 121 children with previously recorded electrically
      evoked auditory brainstem responses (EABR). STUDY DESIGN AND METHODS: Responses
      were evoked by 3 electrodes along the implant array in three groups of children:
      1) postmeningitic, 2) abnormal cochlea, and 3) neither. Intraoperative measures
      were obtained under anesthesia; all other recordings were completed in awake
      children. RESULTS: Intraoperative recordings revealed large nonauditory responses
      in a number of channels, including the midline EABR. Under paralysis, these
      responses disappeared, and clear EABRs were recorded. Similarly, prospective
      postoperative electromyographic (EMG) responses from the facial nerve were found
      in more than 59% (26 of 44) of experienced implant users (Nucleus 24): 31% of
      postmeningitic children (4 of 13), 80% of those with abnormal cochlea (8 of 10),
      and 66% of those with neither (14 of 21). Retrospective analysis of previously
      recorded postoperative EABRs demonstrated facial nerve stimulation in 35% (42 of
      121). In most cases, facial nerve stimulation occurred when levels were
      perceptually loud but comfortable. CONCLUSIONS: 1) Facial nerve potentials can be
      recorded using EMG in a large proportion of cochlear implant users at high levels
      of stimulation. 2) The EABR can be obscured in the presence of facial nerve
      stimulation and care should be taken to distinguish it from the EMG response,
      particularly when auditory brainstem activity is in question. 3) Use of surface
      EMG provides an additional objective measure to ensure the safe and comfortable
      use of cochlear implants.

PMID- 17003732
TI  - Migraine-related vertigo: diagnostic criteria and prophylactic treatment.
AB  - OBJECTIVE/HYPOTHESIS: The objective of this prospective, observational study was
      to evaluate the efficacy of migraine pharmacologic prophylaxis on a group of
      vertiginous patients considered affected by migraine-related vertigo on the basis
      of precise criteria of inclusion. METHODS: Fifty-three patients affected by
      migraine-related vertigo were selected from a cohort of 652 vertiginous patients
      referred to our Dizziness Unit from March 2001 to June 2005. Inclusion criteria
      were at least five vertigo attacks occurred in any period of time or dizziness
      and/or positional vertigo for at least 6 months; migraine, past or present,
      and/or a family history of migraine and/or motion intolerance; and exclusion of
      other causes. Patients were submitted to migraine pharmacologic prophylaxis
      selected on the basis of the characteristics of the patients and of the drug side
      effects. The efficacy of the treatment was evaluated after 6 months by
      questionnaire divided into five outcome categories (resolution, substantial
      control, moderate control, minimal control, no improvement or worsening) and, for
      the patients with recurrent vertiginous attacks, also reporting the percentage
      reduction of the attack frequency. RESULTS: Thirty-six patients completed the
      study and were submitted to analysis of the results: 10 reported complete
      resolution of symptoms, 15 substantial control, 7 moderate control, one minimum
      control and 3 no improvement. Thirty-three of them had recurrent vertigo: 19
      reported complete disappearance of the attacks, 8 reduction of the frequency
      >50%, 5 reduction <50%, and one no reduction. CONCLUSIONS: Migraine prophylactic
      treatment shows encouraging results in patients with migraine-related vertigo
      selected with our criteria of inclusion: 69.3% reported satisfactory control of
      symptoms (sum of complete resolutions and substantial controls) and 81.8% had at
      least a 50% reduction of the vertiginous episodes frequency.

PMID- 17003733
TI  - Evaluation of culture and antibiotic use in patients with pharyngitis.
AB  - OBJECTIVES: The objectives of this study were to evaluate practice patterns for
      treatment of patients with pharyngitis with regard to testing for group A beta
      hemolytic streptococcal (GABHS) infection, frequency of antibiotic use, and
      appropriate choice of antibiotics. STUDY DESIGN: The authors conducted a
      retrospective review of billing data for 10,482 office visits for pharyngitis.
      METHODS: The 2004 billing database for a tertiary institution was queried for
      outpatient visits for pharyngitis or tonsillitis, group A Streptococcus tests
      (GAST), and antibiotic prescriptions filled after the visit. Patients were
      separated by age group and analyzed for the proportion of patients that received
      a GAST and proportion prescribed an antibiotic. Antibiotic prescriptions were
      also analyzed to determine whether they were appropriate for treatment of GABHS.
      RESULTS: A total of 68.7% of all patients and 82.2% of pediatric patients were
      tested for GAST. A total of 47.1% of adult patients and 44.9% of pediatric
      patients received an antibiotic. For adult patients for whom GAST was obtained,
      48.6% were prescribed an antibiotic versus 53.6% of those not tested.
      Streptococcus testing was a significant predictor of antibiotic use (P < .0001),
      whereas age was not (P = .22). A total of 82.1% of all antibiotics prescribed
      were recommended for treatment of GABHS. CONCLUSIONS: Most patients seen for
      pharyngitis were tested for GABHS, but pediatric patients were tested more
      frequently than adults. Patients who received a GAST were less likely to receive
      antibiotics. The rates experienced in our tertiary academic institution are
      higher than previously quoted for community practice. When antibiotics were
      prescribed, they were usually appropriate for the treatment of GABHS based on
      current recommendations.

PMID- 17003734
TI  - A paranasal tumor associated with tumor-induced osteomalacia.
AB  - BACKGROUND: Tumor-induced osteomalacia (TIO) is an extremely rare paraneoplastic
      syndrome associated with mesenchymal tumors in the craniofacial region. METHODS:
      We treated a 24-year-old Japanese woman with paranasal sinus tumor and a low
      serum phosphate level who presented with nasal obstruction and systemic bone
      fractures. Serum fibroblast growth factor 23 (FGF-23) was measured before and
      after surgery. RESULTS: After surgery, her symptoms were resolved and the serum
      phosphate and FGF-23 levels became normalized. CONCLUSION: FGF-23 is thought to
      be a useful diagnostic marker in patients with craniofacial tumors associated
      with multiple systemic fractures.

PMID- 17003735
TI  - 'Bow and lean test' to determine the affected ear of horizontal canal benign
      paroxysmal positional vertigo.
AB  - OBJECTIVE: One of the problems in the management of horizontal semicircular canal
      benign paroxysmal positional vertigo (HSC-BPPV) is the difficulty in determining
      the affected ear using Ewald's second law. The purpose of this study is to
      develop the new "bow and lean test (BLT)" to easily determine the affected ear of
      HSC-BPPV and evaluate its efficiency. METHODS: We compared the efficiency between
      the classic method and BLT in 26 patients with HSC-BPPV. The classic method is
      based on Ewald's second law comparing the intensity of nystagmus or symptoms in
      the head roll test. BLT is based on the direction of both "bowing nystagmus" and
      "leaning nystagmus" at the head's bowing and leaning state in a sitting position.
      The affected ear is the same direction of bowing nystagmus in canalolithiasis and
      the same direction of leaning nystagmus in cupulolithiasis. RESULTS: In 26
      patents (15 canalolithiasis, 11 cupulolithiasis), 3 (11.5%) patients did not show
      a prominent affected ear in the classic method, and 7 (26.9%) patients showed the
      different affected ear between the two methods. All 10 patients were successfully
      treated with just one trial of barbecue rotation based on the affected ear in
      BLT. Three patients did not show any bowing or leaning nystagmus. The side with
      canal paresis in all four patients, who showed significant canal paresis in
      bithermal caloric tests, was equal to the affected ear based on BLT. CONCLUSIONS:
      The "bow and lean test" (also called "Choung's test") is a new method that can
      easily determine the affected ear of HC-BPPV.

PMID- 17003736
TI  - Risk acceptance in laryngeal transplantation.
AB  - PURPOSE: Advancements in the fields of head and neck surgery and immunology have
      paved the way for new quality of life-improving procedures such as larynx
      transplantation. To quantitatively assess the risks versus benefits in larynx
      transplantation, we used a questionnaire-based survey (Louisville Instrument For
      Transplantation [LIFT]) to measure the degree of risk individuals are willing to
      accept to receive different types of transplantation procedures. METHODS: The
      LIFT contains 237 standardized questions incorporating standard gamble and time
      tradeoff outcome measures as well as questions assessing body image perception,
      depression, self-esteem, optimism, socially desirable responding, and
      demographics. Respondents were questioned on the extent to which they would trade
      off specific numbers of life-years, or sustain other costs, in exchange for
      receiving seven different types of transplant procedures. For this study, we
      questioned 243 individuals in three study populations with differing life
      experiences: healthy individuals, organ transplant recipients, and
      laryngectomees. RESULTS: All populations questioned perceived risks differently
      based on their varied life experiences and would accept differing degrees of risk
      for the different transplant procedures. Organ transplant recipients were the
      most risk-tolerant group, whereas laryngectomees were the least risk-tolerant.
      CONCLUSIONS: By questioning individuals with life experiences directly relevant
      to the risks and benefits associated with larynx transplantation, this study
      provides an empiric basis for assessing risk versus benefit in this new quality
      of life-improving procedure.

PMID- 17003737
TI  - Summating potential-action potential waveform amplitude and width in the
      diagnosis of Meniere's disease.
AB  - OBJECTIVES: It has been suggested that analyzing the width and amplitude of the
      summating potential-action potential (SP-AP) waveforms can increase the
      sensitivity of electrocochleography. The objective of this study was to evaluate
      the ratio of SP to AP amplitude (SP/AP) and SP-AP waveform width, as well as the
      AP latency difference to condensation and rarefaction clicks, for the diagnosis
      of Meniere's disease. STUDY DESIGN: This was a prospective, controlled study.
      METHODS: We used transtympanic electrocochleography to evaluate 21 patients with
      definite Meniere's disease and 19 normal-hearing patients with other
      cochleovestibular disorders, comparing SP/AP, AP latency difference, and SP-AP
      waveform widths as well as calculating the diagnostic sensitivity of these
      parameters. RESULTS: Mean SP-AP waveform width was 1.89 ms in the study group and
      1.58 ms in the control group. Mean SP/AP was 0.37 in the study group and 0.22 in
      the control group. The mean product of SP-AP waveform width and SP/AP was 75.26
      ms% in the study group and 34.60 ms% in the control group. Mean AP latency
      difference was 0.13 ms in the study group and 0.07 ms in the control group. For
      the parameters evaluated, the differences between the groups were statistically
      significant. In the study group, the sensitivities for the width of the SP-AP
      waveform, the SP/AP, and the AP latency difference were 33.3%, 52.4%, and 23.8%,
      respectively. CONCLUSIONS: The use of the parameters evaluated did not increase
      the sensitivity of the electrocochleography, whether used in isolation or in
      conjunction with the SP/AP. Determining SP/AP presented the greatest sensitivity.

PMID- 17003738
TI  - The role of intensity upon pitch perception in cochlear implant recipients.
AB  - OBJECTIVES: Pitch plays a key role in the perception of speech and music, the
      recognition of a speaker's voice, and in analyzing complex auditory patterns. To
      date, little consideration has been given to the influence of stimulation level
      on pitch perception. The aim of this study was to investigate the impact of a
      sound's intensity on pitch perception in cochlear implant recipients using
      monopolar stimulation. STUDY DESIGN: Thirteen patients with an average implant
      use of 4.13 years took part in this study. All patients were implanted with MedEl
      Combi 40/40+ cochlear implants. METHODS: In the first part of the study, we
      performed a pitch ranking procedure to confirm that all patients were able to
      judge pitch changes. Using a visual scale, study participants were then asked to
      compare the pitch of an intensity-constant reference tone with the pitch of a
      test tone of varying intensity. RESULTS: Eleven (85%) patients were found to
      perceive a clear change in pitch with changing stimulus intensity. Statistical
      analysis showed a strong positive correlation in 10 patients (correlation
      coefficients between 0.99 and 0.71) and a strong negative correlation in 1
      patient (r = -0.92). CONCLUSIONS: The results suggest that a distinct
      relationship exists between pitch perception and intensity of the stimulus. To
      date, speech coding strategies do not support these findings. Nevertheless, we
      believe that for the optimized most natural perception of sounds, especially
      music, the described particularities of pitch perception need to be respected,
      and further investigations on this topic are necessary.

PMID- 17003740
TI  - The ACE-DD genotype is associated with endothelial dysfunction in postmenopausal
      women.
AB  - OBJECTIVE: To evaluate the effects of the angiotensin-converting enzyme (ACE)
      insertion/deletion (I/D), the angiotensinogen M235T and the angiotensin II type 1
      receptor A1166C polymorphisms, and hormone therapy used on endothelial function
      in postmenopausal women without manifestation of coronary artery disease. DESIGN:
      Sixty-four postmenopausal women (42 hormone therapy users and 22 hormone therapy
      nonusers) without clinical manifestation of coronary artery disease were
      evaluated using external vascular ultrasonography to measure endothelium
      dependent (hyperemic response, flow-mediated dilatation) and -independent
      (nitroglycerin) dilatation. Genotypes were determined by polymerase chain
      reaction amplification. RESULTS: Women with the ACE-DD genotype displayed a lower
      flow-mediated dilatation compared to those with the ACE-II genotype (8.4% +/-
      3.9% vs 12.6% +/- 5.4%, P = 0.04). Endothelial function was not associated with
      the angiotensinogen M235T and anglotensin II type 1 receptor A1166C
      polymorphisms. ACE polymorphism seems to modulate endothelial function among
      postmenopausal women without hormone therapy (8.2% +/- 5.1% vs 18.4% +/- 5.9% for
      the DD and the II genotype, respectively, P = 0.02). However, in hormone therapy
      users, flow-mediated dilatation was similar according to the ACE genotypes.
      CONCLUSIONS: Our findings suggest that ACE-I/D polymorphism is related to
      endothelial dysfunction in postmenopausal women. Furthermore, a potential
      interaction between estrogen users and ACE polymorphism on endothelial function
      may be present.

PMID- 17003739
TI  - Sexual functioning throughout menopause: the perceptions of women in a British
      cohort.
AB  - OBJECTIVE: Previous studies on menopausal transition and sexual functioning have
      mixed findings. Most are cross-sectional, exclude hormone therapy users and
      hysterectomized women, and are unable to separate the effects of age from
      menopause or account for psychosocial, vasomotor, and somatic factors. We examine
      relationships between women's reports of a change in sex life and difficulties
      with intercourse and their experience of menopausal transition, use of hormone
      therapy, and hysterectomy. DESIGN: A British cohort study with 1,525 women were
      followed since their birth in 1946 and annually from age 47 to 54 years. The
      outcome measures were self-reported change in sex life and difficulties with
      sexual intercourse over 8 consecutive years. RESULTS: Compared with women who
      remained premenopausal, peri- and postmenopausal women reported a decline in sex
      life (mean difference [95% CI]: perimenopausal, -0.1 [-0.2 to -0.03]; became
      postmenopausal, -0.1 [-0.2 to -0.1]) and were more likely to report difficulties
      with intercourse (perimenopausal, 0.6 [0.1 to 1.1]; postmenopausal, 1.0 [0.5 to
      1.5]) beyond the effects of aging and other psychosomatic factors. Women reported
      difficulties with intercourse more often if they had been on hormone therapy for
      more than a year (0.5 [0.03 to 1.0]) or if they had undergone a hysterectomy (0.6
      [0.1 to 1.1]); no differences were found for change in sex life. For both
      outcomes, vaginal dryness was the major risk factor. Married women were also more
      likely to report adverse outcomes. Somatic symptoms and hot flushes/cold sweats
      were associated with difficulties with intercourse, whereas psychological
      symptoms, stressful lives, increasing age, and smoking were associated with a
      decline in sex life. CONCLUSIONS: Menopausal transition status had an independent
      effect on the reported change in sex life and difficulties with intercourse. The
      results support health professionals in their development of management
      strategies that (a) consider treatments directly for vaginal dryness, (b)
      identify somatic symptoms for difficulties with intercourse, (c) investigate
      psychological factors for a reported decline in sex life, and (d) for both
      outcomes, consider the potential role of intimate partners.

PMID- 17003741
TI  - [Training for residents in obstetrics and gynaecology: Concerning on-site visits
      for evaluation].

PMID- 17003742
TI  - [Endometrial hyperplasia: A review].
AB  - Endometrial hyperplasias can be divided into two categories based on the presence
      or absence of cytological atypia and further classified as simple or complex
      according to the extent of architectural abnormalities. They are usually
      diagnosed because of irregular bleeding in perimenopause. Hysteroscopy with a
      biopsy gives a more accurate diagnosis than transvaginal ultrasonography,
      sonohysterography, or blind curettage. Endometrial hyperplasias with no
      cytological atypia, regarded as a response to unopposed endogenous estrogenic
      stimulation, are normally treated with progestins. The intra-uterine route
      (levonorgestrel intra-uterine system) is more effective and better tolerated than
      the oral route. Either conservative surgery (endometrial resection, thermal
      ablation) or radical surgery (hysterectomy) in the case of other genital diseases
      is performed on women who did not respond to medical treatment. Endometrial
      hyperplasias with cytological atypia, considered as intra-epithelial neoplasias,
      are traditionally treated by hysterectomy. The absence of management protocols in
      the literature offers various treatment options and indications. Gonadotropin
      releasing hormone agonists, danazol, or aromatase inhibitor are effective, but
      have adverse effects and are expensive. Endometrial ablation can be performed as
      a first line therapy in women suffering from bleeding related to hyperplasia
      without cytological atypia. Medical treatment may be offered to young women
      suffered from hyperplasias with cytological atypia and desiring pregnancy.

PMID- 17003743
TI  - [Male and female sterilization techniques: Summary of ANAES assessments (May
      2005)].
AB  - OBJECTIVE: To summarize assessments carried out by ANAES on male and female
      sterilization techniques. The summary was requested by the French Health
      Directorate after the law authorizing sterilization as a means of contraception
      was passed. RESULTS (FEMALE STERILIZATION): (i) EFFICACY of tubal ligation,
      electrocoagulation, clips or rings: the annual pregnancy rate is 0-2% depending
      on the study, with no significant difference between techniques. No data were
      found on fimbriectomy. (ii) EFFICACY of a hysteroscopically placed micro-insert
      device: no pregnancies were observed in patients with bilateral tube obstruction
      diagnosed by hysterosalpingography at 3 or at 6 months after placement (placement
      rate: 87-89%). (iii) SAFETY of tubal ligation, electrocoagulation, clips or
      rings: (a) By approach: There was no difference in the incidence of major
      complications between laparoscopy and minilaparotomy but there were significantly
      fewer minor complications with laparoscopy than with minilaparotomy. There were
      significantly more major complications with culdoscopy than with minilaparotomy
      and significantly more minor complications than with laparoscopy. (b) By
      operative technique: major and minor complications were significantly more common
      with the Pomeroy technique than with electrocoagulation; the difference could be
      due to the approach used. No data were available on fimbriectomy. (iv) SAFETY of
      a hysteroscopically placed micro-insert device: there were 11 cases of myometrial
      or tubal perforation among 734 patients (with device displacement into the
      peritoneal cavity in 3 cases). RESULTS (MALE STERILIZATION): (i) EFFICACY:
      efficacy varied from 84% to 100% depending on the approach and the mode of vas
      deferens obstruction. There was no significant difference in efficacy according
      to approach (transcutaneous or scrotal). However, no conclusion could be drawn on
      the comparative efficacy of the occlusion techniques used from published data.
      (ii) SAFETY: the rate of postoperative complications was low, below 10% in most
      series. Complications were benign and only rarely necessitated surgical revision.
      CONCLUSION: The advantage of sterilization methods is that they lack any
      permanent contraindication. They should be presented as being generally
      irreversible. Fimbriectomy is not recommended for female sterilization.
      Laparoscopy is the preferred approach. Sterilization by hysteroscopic placement
      of a micro-insert device should be restricted to cases presenting a risk on
      laparoscopy; the technique should be re-assessed in 2006. The two approaches used
      for male sterilization are technically similar and do not seem to differ in
      efficacy. The Public Health Code states that "Fallopian tube or deferens duct
      ligation for contraceptive purposes is not allowed in minors" and that ligation
      "cannot be performed unless the adult involved has given his/her informed and
      motivated consent, expressed after taking into consideration clear, complete
      information on the consequences of the procedure". A waiting period of four
      months must follow the moment the decision to sterilize is taken and consent is
      given. An informed consent form must be signed. Sterilization in young or
      nulliparous women should be proposed with the greatest prudence and with many
      reservations.

PMID- 17003744
TI  - [Trans-obturator urethral sling for surgical correction of female stress urinary
      incontinence: Outside-in (Monarc) versus inside-out (TVT-O). Are both ways
      safe?].
AB  - INTRODUCTION: The originally described outside-in procedure for the trans
      obturator route was later turned inside-out. We wanted to demonstrate the safety
      of the two techniques through personal and published experience. MATERIAL AND
      METHODS: Non-randomized, prospective, observational, open-label, longitudinal
      study of 100 female patients (50 TVT-O and 50 Monarc). All the female patients
      presented with isolated stress urinary incontinence. Only 4 patients presented
      with mixed incontinence in the Monarc (MON) group. Sphincter incompetence was
      observed 4 times in the MON group and 3 times in the TVT-O group. All the
      patients underwent surgery under assisted local anesthesia in a day-hospital
      setting. Only those patients presenting with patent established urinary
      incontinence, corrected by the TVT test, underwent surgery. Post-operative
      control was conducted at 3 months and 1 year. RESULTS: The duration of
      hospitalization was 10 h for 48 patients in the MON group and 49 in the TVTO
      group. The only per-operative complication was a vaginal perforation in the
      lateral angle of the vagina for a MON patient. Early post-operative complications
      were observed in the MON group: 3 cases of urinary tract infection, 1 of
      transient urine retention, 3 of pain in the thighs spontaneously resolving within
      4 days and 1 of permanent pain in one leg at time 1 year, which remained
      bearable. For the TVTO group the post-operative complications consisted in: 1
      case of urinary tract infection, 1 of transient retention and 4 of pain in the
      thigh. No hematoma was reported in either group. Among the late complications,
      the de novo symptoms included 1 case of imperious urges to urinate in the TVTO
      group and objective dysuria in 2 cases in the MON group vs. 7 in the TVTO group.
      There was no statistically significant between-group difference in the
      complications. No tape exposure was observed. Overall, the recovery rate was 90%
      at 1 year for MON vs. 94% for TVTO (p = NS) with 2 cases of recurrence between 3
      months and 1 year in that series. Mixed incontinence was corrected at time point
      1 year in 75% of cases for MON, with 1 case of recurrence in the year. For the
      patients presenting with sphincter incompetence, competence was maintained at 3
      months and 1 year in all cases in the MON group. The 3 TVT-O were cured at 3
      months, but 2 recurrences were observed at 1 year. All patients, except one, were
      satisfied at time point 1 year and those who had sexual relations (54%) did not
      report any disorder at time point 1 year. DISCUSSION: The cadaveric studies by
      advocates of the outside-in technique show a vascular and nervous risk which has
      received little attention in terms of complications in the literature. Post
      operative leg pain is encountered with both techniques and usually is transient.
      CONCLUSION: Our experience, like that reported in the literature, shows that the
      two trans-obturator access routes are equally safe. The clinical results would
      appear to be equivalent, in terms of recovery, to the rates obtained with
      retropubic TVT.

PMID- 17003745
TI  - [Chikungunya infection in pregnancy: Evidence for intrauterine infection in
      pregnant women and vertical transmission in the parturient. Survey of the Reunion
      Island outbreak].
AB  - PURPOSE: Since February 2005, an outbreak of Chikungunya virus (CHIKV) infections
      occurred in Reunion Island. It is transmitted by the Aedes albopictus mosquito.
      Neonatal cases observations suggest possible fetal transmission during pregnancy.
      MATERIAL [corrected] AND METHODS. Observations made in 160 pregnant mothers
      infected by CHIKV between June 1, 2005 and February 28, 2006, in the south of
      Reunion island were recorded. RESULTS: Three of nine miscarriages before 22 weeks
      of gestation could be attributed to the virus. 3,829 births took place during
      this time. Among the 151 infected women, 118 were viremia negative at delivery,
      and none of the newborns showed any damage. Among the 33 with positive viremia at
      delivery, 16 newborns (48.5%) presented neonatal Chikungunya. DISCUSSION: Though
      fetal contamination risks appear to be rare before 22 weeks of gestation, they
      are potentially dangerous. After 22 weeks gestation, newborns infection occurs if
      the mother is viremia positive at delivery. Transplacental transmission is
      suspected, but the pathogenic mechanism remains unknown.

PMID- 17003746
TI  - [First breech twin pregnancy: Can we still accept a vaginal delivery? Comparative
      study of perinatal outcome with attempt of vaginal delivery versus planned
      cesarean: 166 cases].
AB  - OBJECTIVES: To evaluate practices and perinatal outcome in planned routes of
      delivery for first breech twins. MATERIALS AND METHODS: A retrospective study in
      first breech twin pregnancies with a gestational age of at least 35 weeks at
      onset of labor. Maternofetal pathologies known to be associated with a poor
      neonatal outcome were excluded. A low neonatal outcome was defined by at least
      one of the following criteria: neonatal death, 5-minute Agar Score < 7, cord
      blood pH < 7.10, traumatic neurological injuries, admission in neonatal intensive
      unit care. Neonatal and maternal outcomes were compared between attempt of
      vaginal delivery (AVD) and planned cesarean section (PCS). RESULTS: Among 166
      included patients, an AVD has been performed in 105 cases (63.3%) and a PCS in 61
      (36.8%). In AVD group, 46 women (43.8%) delivered vaginally. Low neonatal outcome
      was not significantly different in AVD group compared with PCS group (9 (8.6%)
      versus 6 (9.8%); p = 0.78 for the first twin and 7 (6.7%) versus 2 (3.3%); p =
      0.49 for the second twin). There was no significant difference in maternal
      morbidity between the two groups. As a general rule, established practices for
      deciding route of delivery and labor have been applied in our department.
      CONCLUSION: No excess of neonatal risk in AVD group compared with PCS was
      observed. These results could be extrapolated to centers applying a careful
      protocol to decide the route of delivery and labor practices.

PMID- 17003747
TI  - [Management of in utero foetal death: Which assessment to undertake?].
AB  - OBJECTIVE: To assess the value of para-clinical exams prescribed in case of in
      utero foetal death, to result in the establishment of a new algorithm of
      diagnostic tests. MATERIALS AND METHODS: A retrospective analysis on a series of
      106 stillbirths gathered between September 1989 and December 1998 in the
      obstetrical and gynaecological department of the Lausanne University Hospital
      which is a tertiary centre. Stillbirth was defined as foetal death occurring as
      from the date of foetal viability. Thus, only pregnancies from 24 weeks and
      onwards were included in this series. We excluded all stillbirths occurring
      during medical termination of pregnancy and cases with incomplete data files. The
      Fretts' classification was used. The different exams asked by the physician were
      screened and we analysed their pertinence to determine the aetiological diagnosis
      for each case. The search for significant risk factors was also taken into
      account. We compared our management of in utero foetal death with data from the
      literature to propose a new algorithm. RESULTS: The aetiology of in utero foetal
      death could be attributed in ninety percent of the cases. The principal causes
      were in utero growth retardation (19.8%), foetal congenital and chromosomal
      anomalies (18.9%), infections (15.1%), placental abruption (7.5%), preeclampsia
      (5.6%), maternal diabetes (3.8%). The remaining 18.9% are divided in to
      miscellaneous causes. In 10.4% of the cases we could not find any explanation to
      the death of the foetus. The exams that yielded the most information when done
      were: foetal autopsy which was abnormal in 92.7%, placental investigation which
      was abnormal in 93% and the babygramme (X-ray of the foetal skeleton) which was
      abnormal in 53%. Maternal serology for infections was informative in 6.6% of the
      cases. CONCLUSION: We present here a protocol for the diagnostic management of
      stillbirth which is differentiated according to the circumstances surrounding the
      event. This should prove useful to reduce superfluous tests.

PMID- 17003748
TI  - [Marfan's syndrome and pregnancy].
AB  - The Marfan's syndrome is an autosomal dominant genetic disorder resulting in a
      diminished strength of connective tissue. The ocular, skeletal and cardiovascular
      systems are mostly at risk. Principal complications of the disease are aortic
      dilatation and the risk of acute dissection. Pregnancy increases this risk. Based
      on the experience of our obstetrics department and after reviewing medical
      literature, we have tried to establish guidelines for obstetric care adapted to
      pregnant patients affected by Marfan's syndrome. Women with aortic root > 40 mm
      should avoid pregnancy. In all cases B-adrenergic receptor blockers must be used
      as soon as possible. Because there is a 50% risk that offspring will inherit the
      syndrome, prenatal diagnosis should be suggested. In addition to usual pregnancy
      monitoring, echocardiography should be performed every 3 months as well as 2
      months after delivery. No increase of obstetrical complications has been shown in
      these patients. Route of delivery also depends on the diameter of the aortic
      root: vaginal delivery is warranted if the aortic root is<40; cesarean section
      should be performed in the other cases. Thus, with appropriate supervision, women
      with Marfan's syndrome will tolerate pregnancy without any adverse effect.

PMID- 17003749
TI  - [Intra-uterine arteriovenous malformations].
AB  - Intra-uterine arteriovenous malformations are a possible etiology of persistent
      metrorrhagia especially in the event of a history of miscarriages, cornuale
      pregnancy, molar pregnancy or gravidic trophoblastic diseases. We report 4 cases
      of patients having an intra-uterine arteriovenous malformation. The diagnosis of
      such lesions calls upon first intention Doppler echography. This diagnosis is
      confirmed thereafter by angiography. The first intention treatment is
      embolization which can save time if carried out at the same time as the
      angiography. This treatment is rapid and final, enabling the patients to have
      other pregnancies later on. An echographic follow-up, according to a schedule
      which remains to be defined, is necessary in order to check the good involution
      of this type of vascular malformation.

PMID- 17003750
TI  - [Uretrovaginal reflux during micturition: A case report].
AB  - Reflux into vagina during micturition is a rare phenomenon in adults. We report a
      case of a 22-old-year woman who presented with intravaginal influx of urine. This
      case illustrates the anatomic basis, diagnostic examinations and clinical and
      bacteriological implications of this phenomenon.

PMID- 17003751
TI  - [Botulism and pregnancy].
AB  - Botulism during pregnancy is uncommon and raises concern due uncertainty about
      fetal impairment. This type of situation has not been reported to date. Treatment
      is basically symptomatic and based on nursing care. The prognosis is tightly
      correlated with the maternal status. Dietary hygiene is the basis of prevention.
      We describe a case of botulism occurring during the second quarter of pregnancy.

PMID- 17003752
TI  - [The repaired face, and after?].

PMID- 17003753
TI  - [Attempting to define cranial injury].

PMID- 17003754
TI  - [Mild brain injuries: definition, classifications and prognosis].
AB  - Brain injuries may be graded into mild, moderate and severe depending on clinical
      and radiological criterions. Mild brain injuries (MBI) are usually defined by an
      initial unconsciousness limited to 30 minutes, a Glasgow score between 13 and 15,
      the absence of intra-cranial lesion on the CT scan, a post-traumatic amnesia
      period between one and 24 hours depending on the authors. The consequences of a
      MBI may be simple but the injured often suffer from a transitory post-concussive
      syndrome. Traumatic stress states are a well known pathology and consist in a
      psychological reaction against the trauma. The acute traumatic stress may or may
      not run its course to a chronic post-traumatic stress disorder, formerly called
      post-traumatic neurosis.

PMID- 17003755
TI  - [Epidemiology of the mild and moderate brain injuries].
AB  - Unlike severe head injuries upon which much attention is focused, mild or
      moderate brain injuries are not or not well known and often neglected in
      maxillofacial surgery. Nevertheless, they are frequent in our routine facial
      traumatology activity. Studying the epidemiological data shows that mild brain
      injuries account for 64 to 94% of all head injured patients whereas moderate
      injuries occur in 3 to 23%. Furthermore, owing to their frequent occurrence,
      their high potential for sequelae and because they especially affect young
      people, they are a real public-health problem.

PMID- 17003756
TI  - [Clinical scoring scales for brain injury].
AB  - The development of data processing techniques has enabled the establishment of
      large databanks on brain injury. Clinical features are described with clinical
      scoring scales, the main one being the Glasgow Coma Scale. Three types of patient
      response are analyzed: eye opening, oral answers, active muscular reaction. The
      advantages and disadvantages of each are presented. Others scales have been
      proposed but are not in common use. Several classifications have been established
      combining depth and length of coma. Post-traumatic amnesia, i.e. the period of
      time running from the injury to recovery of anterograde memory, constitutes the
      most important parameter in the classification of these injuries. Generally,
      three gravity grades are used: mild, moderate and severe brain injuries.
      Knowledge of the prognosis is essential for determining the most appropriate
      medical care and is directly related to the quality of the collected data. Five
      outcome categories can be described.

PMID- 17003757
TI  - [Neuroradiological investigations in mild brain injuries: state of the art and
      practical recommendations].
AB  - OBJECTIVES: To clarify the contribution of each technique of neuroradiological
      and nuclear medicine investigations after mild brain injuries. To analyze the
      pathophysiological mechanisms of the lesions. To update indications for imaging
      techniques in the short or long term management. To define the practical
      recommendations. METHOD: The international databases were consulted for each
      neuroradiological technique; the most valuable articles were retained for study
      (PubMed, ). RESULTS AND DISCUSSION: Standard skull X-rays are obsolete.
      Craniofacial (bony windows) and brain CT-scan (parenchymal windows) is the most
      efficient diagnosis tool in the acute phase because of its accessibility. Brain
      MRI is less accessible in the emergency setting but is feasible in some centers.
      It is the best choice in the first weeks following mild brain injury but may be
      normal. Taking into account the limitations of morphological imaging, functional
      imaging techniques (SPECT, fMRI, PET-scan) are necessary as they may show axonal
      damage or brain atrophy. There is however the problem of availability. SPECT is
      the most accessible. Spectro-MRI is promising. In spite of progress in
      neuroradiological investigation methods, the neuropsychological evaluation and
      multi-disciplinary treatment of these patients by a skilled team remains of
      utmost importance.

PMID- 17003758
TI  - [Long-term functional and aesthetic sequelae after complex facial trauma
      associated with a mild brain injury].
AB  - INTRODUCTION: Most victims of complex facial trauma will have permanent sequelae.
      The goal of our work was to evaluate, by means of a retrospective study, the long
      term sequelae in these patients. MATERIAL AND METHOD: 102 victims of complex
      facial trauma were treated in our department between 1995 and 2000. Twenty-four
      could be re-examined in 2006 in order to evaluate their long-term sequelae. All
      the patients suffered a mild brain injury. RESULTS: The overall satisfaction rate
      was good (19/24), but all patients presented either functional or aesthetic
      sequelae. The major functional sequelae were dental lost (17/24), sensory
      impairment of the trigeminal nerve (15/24), partial or complete loss of vision
      (10/24), pain (10/24), hypo- or anosmia (9/24), stenosis of the lacrimal ducts
      (8/24) and symptomatic deviation of the nasal septum (7/24). The main esthetic
      sequelae were facial scarring (23/24), facial asymmetry (13/24), dystopia of the
      eyeball (11/24) and modification of the aspect of the nose (10/24). DISCUSSION:
      The prognosis of severe facial trauma is highly dependent on the quality of the
      initial pluridisciplinary care. Secondary revision procedures are technically
      more difficult and only enable partial resolution of persisting sequelae. Thus,
      primary single-course surgical procedures should be a priority, recognizing that
      complete recovery is almost always illusory.

PMID- 17003759
TI  - [Long-term functional, psychic, social, occupational and judiciary outcome in
      victims of facial trauma].
AB  - The cases of 102 people who suffered brain and facial trauma were reviewed,
      noting the long-term outcome at more than 5 years. Results of complete physical
      examinations performed by a surgeon and an internist were available for 25
      patients. Data noted were: circumstances of the traumatic event, classification
      of brain injuries, sensory and sensorial disorders, and persistent pain,
      psychological trauma, social and occupational consequences and at the final legal
      and financial compensation. These data were summarized in tables to facilitate
      discussion of the findings.

PMID- 17003760
TI  - [Mild head trauma: complications and acousticovestibular sequelae].
AB  - Head injury with fracture of the petrous bone is frequent and directly related to
      the development of human activity. Head trauma is associated with nearly 75% of
      traffic accidents; 5% of them with petrous bone fracture. Based on a clinical
      case, the acute injuries and secondary acoustic or vestibular sequelae after low
      energy cranio-cerebral trauma are discussed here. The subject was a victim of a
      low-energy head trauma with brief loss of consciousness and translabyrinthine
      fracture of the petrous bone. This fracture caused invalidating equilibrium
      disorders related to a perilymphatic fistula. These disorders persisted for 3.5
      years and required several hospitalizations and three surgical procedures. The
      acoustic problems progressed towards cophosis and persistent and invalidating
      tintinus. We discuss the pathogenesis and treatment of these different sequelae
      of the middle ear as well as the external lesions. Among labyrinthine
      involvement, especially unilateral destruction, fistulization, concussion, and
      post concussion syndrome are especially descripted. Bony dislocations dominate
      middle ear sequelae. We also discuss the medicolegal problems associated with
      this type of pathology.

PMID- 17003761
TI  - [Ocular injuries in mild facial trauma].
AB  - Ocular contusions are common and cause significant morbidity. The mechanism of
      ocular contusion is a decrease in the length of the anterioposterior axis whereas
      the transversal axis increases. Epidemiology data shows that young men are most
      injured in relation with sports, aggression, work, or car or work accidents.
      Injury to the ocular surface (conjunctiva and cornea) is minor. The iris is very
      frail, usually leading to hyphema which can progress to glaucoma. A cataract can
      appear after a contusion but usually years after the trauma. Final visual acuity
      can be compromised by retinal contusion or retinal detachment (due to a retinal
      dehiscence or post-traumatic dialysis). The worst outcome is optic neuropathy.
      The most difficult task is to predict visual acuity after the initial ocular
      lesion.

PMID- 17003762
TI  - [Psychological aspects of facial trauma].
AB  - The anatomic lesions resulting from facial trauma have serious psychological
      implications. The topic can be divided into three parts. First, the psychological
      trauma begins by a simple conception of the psychic structure. Secondly, an
      external crust protects an inner structure whose role is to maintain a vital
      function and a pleasure function. Thirdly, the face materializes these two
      functions. Facial trauma totally disrupts the external crust with staggering
      psychic implications, releasing the archaic process of survival. After this
      initial event, a second step is required where the trauma is interiorized leading
      to a highly variable clinical course which involves recovery, disturbed memory,
      and a depressive syndrome. The clinical manifestations and possibilities for
      preventing the post-commotional syndrome are also discussed together with the
      psychological disorders implied with facial traumatism: disorders linked to the
      perception of the face, esthetic damage, neurological and sensorial disorders.
      The course is basically linked to the personality of the patient.

PMID- 17003763
TI  - [A therapeutic approach: the "Maxillo Family"].
AB  - For patients with severe facial injuries, global management from trauma to
      "cure", is the leitmotif in the department of maxillofacial surgery of Besancon.
      The progressive development of therapy groups led to the creation of the "Maxillo
      Family" which is more or less modelled after well known "Gueules Cassees" French
      Association. We also created the "Journal of Maxillo" in which every injured
      patient can write his own story. This seems to be a very good therapeutic
      approach not only from the patients' point of view but also for practitioners and
      nurses. The testimony of a young woman victim of a dramatic accident with severe
      facial injury illustrates the interesting aspects of this therapeutic approach.

PMID- 17003764
TI  - [Neuropsychology and forensic assessment in brain injured patients].
AB  - Neuropsychology, which deals with the relationships between upper mental
      functions and brain structures is directly involved with psychiatric and
      psychological disorders and thus constitutes one of the major domains of
      cognitive sciences. The impairment of upper mental functions is evident after
      severe brain injuries causing significant motor deficits. However, it is becoming
      increasingly evident that even mild or moderate brain injuries can cause sequelae
      which are difficult to analyze and quantify clinically. These sequelae constitute
      an "invisible handicap" which may greatly interfere with the patient's
      professional, relational and social life. The neuropsychological evaluation must
      be systematic and complete and has to be carried out with a sufficient hindsight
      (two to three years after the trauma) using neuropsychological and behavioural
      deficiency evaluation scales. Psychometric tests are also necessary. The data
      obtained from this evaluation must be correctly interpreted and constitutes the
      main exhibit in the forensic examination of the brain injured patient.

PMID- 17003766
TI  - [Total work disability: a national inquiry in France].
AB  - Physicians are often asked to draft a descriptive medical certificate for victims
      of traumatic maxillofacial injuries. Among other requisites, this certificate
      must mention the subject's total work disability. If the injury results from
      intentional or unintentional assault and battery, the duration of the work
      disability will determine the competence of the court that will try and condemn
      the perpetrator. Thus the total work disability certificate has penal value and
      should be used only for this purpose. Using the data acquired from a national
      inquiry in France, we evaluated common practices among a panel of maxillofacial
      teams concerning the information mentioned on the initial medical certificate
      and, in particular, the duration of work disability allocated for the most
      frequent facial fractures. The aim of this study was to establish, based on the
      observed practices, whether it would be licit to propose a total work disability
      scale for maxillofacial trauma.

PMID- 17003765
TI  - [Sequelae of dental trauma: forensic medical aspects].
AB  - Dental trauma is a frequent condition which may occur alone or in combination
      with craniofacial trauma and/or other injuries. Many factors influence the
      gravity of the trauma and subsequent prognosis including age, anterior state,
      trauma etiology, treatment and follow up. In order to establish a prudent
      provisional or definitive expertise, the medical expert must have a panoramic
      view of the trauma. Time should be taken to consolidate facts and estimate
      prejudices on sound evidence. In certain cases outcome can be predicted. The
      medical expert should provide advice and counselling both for the patient and the
      mandating authority. In this article, iatrogenic dental accidents occurring
      during anesthesia or extraction will not be discussed.

PMID- 17003767
TI  - [Mild brain injury: forensic sciences and indemnification].
AB  - Victims of mild trauma brain injury may develop post-concussive symptoms in an
      inverse proportion to the organic damages leading to difficulties in their
      social, occupational and family activities. Proving the link which exists between
      the trauma and its consequences is a difficult task and insufficient methods for
      evaluating post-concussive symptoms make it very difficult to demonstrate the
      cause and effect relationship. The judge's assessment is essential to avoid the
      nearly systematic but wrong diagnosis of pathological predispositions of the
      patient. It is particularly important to improve the nomenclature of the
      different kinds of injuries to reach a better indemnification for those patients
      who suffer from their trauma their entire life.

PMID- 17003769
TI  - A guide for diagnostic evaluations.
AB  - Accurate diagnostic tests have a key role in patient management and the control
      of most infectious diseases. Unfortunately, in many developing countries,
      clinical care is often critically compromised by the lack of regulatory controls
      on the quality of these tests. The information available on the performance of a
      diagnostic test can be biased or flawed because of failings in the design of the
      studies which assessed the performance characteristics of the test. As a result,
      diagnostic tests are sold and used in much of the developing world without
      evidence of effectiveness. Misdiagnosis leading to failure to treat a serious
      infection or wasting expensive treatment on people who are not infected remains a
      serious obstacle to health.

PMID- 17003770
TI  - Ensuring quality and access for malaria diagnosis: how can it be achieved?
AB  - The replacement of conventional antimalarial drugs with high-cost, artemisinin
      based alternatives has created a gap in the successful management of malaria.
      This gap reflects an increased need for accurate disease diagnosis that cannot be
      met by traditional microscopy techniques. The recent introduction of rapid
      diagnostic tests (RDTs) has the potential to meet this need, but successful RDT
      implementation has been curtailed by poor product performance, inadequate methods
      to determine the quality of products and a lack of emphasis and capacity to deal
      with these issues. Economics and a desire for improved case management will
      result in the rapid growth of RDT use in the coming years. However, for their
      potential to be realized, it is crucial that high-quality RDT products that
      perform reliably and accurately under field conditions are made available. In
      achieving this goal, the shift from symptom-based diagnosis to parasite-based
      management of malaria can bring significant improvements to tropical fever
      management, rather than represent a further burden on poor, malaria-endemic
      populations and their overstretched health services.

PMID- 17003771
TI  - Complete medulla/cervical spinal cord transection after atlanto-occipital
      dislocation: an extraordinary case.
AB  - STUDY DESIGN: Case report. SUMMARY OF BACKGROUND DATA: Traumatic atlanto
      occipital dislocation (AOD) with a complete medulla/spinal cord transection is
      rare and believed to be fatal owing to the high level of the spinal cord injury.
      Clinical outcome is poor. Consequently, relatively few case reports of adult
      patients surviving this injury appear in the literature. OBJECTIVES AND RESULT:
      We present the case of a 20-year-old male, who sustained an AOD with a complete
      medulla/spinal cord transection in a motorcycle accident to discuss the
      possibility of long-term survival with this condition. The patient underwent
      occipito-cervical stabilization. With an Injury Severity Score of 75, by
      definition unsurvivable, the patient is 16 months after the injury, ventilated
      and fully dependent for all care. CONCLUSION: Long-term survival following AOD
      with a complete medulla/spinal cord transection is possible if immediate
      resuscitation at the scene is available. Nevertheless, it remains questionable
      whether or not a patient with such a devastating injury and without any prospect
      of functional recovery should be kept alive under all circumstances.

PMID- 17003772
TI  - Perceptions of issues associated with the maintenance and improvement of long
      term health in people with SCI.
AB  - STUDY DESIGN: Qualitative design using focus groups. OBJECTIVE: To explore the
      perceptions of people with SCI and their caregivers about information needs and
      service delivery options that may assist them to maintain or improve their long
      term health. SETTING: Province wide project in Alberta, Canada. METHODS: Eight
      focus groups were conducted; five with community dwelling people with SCI and
      three with unpaid caregivers (family and friends). Content analysis was used to
      identify categories and themes arising from the data. RESULTS: The findings from
      the study are broader than the original objective to explore information needs
      and service delivery options to promote long-term health. The participants more
      globally discussed factors that contribute to or provide barriers to their long
      term health. Those factors are captured in five categories, including readiness,
      information pathways, community health care, health promotion, and contextual
      factors. A framework that illustrates the relationships between categories was
      constructed. CONCLUSION: The framework identifies areas to target in programmes
      designed to reduce or prevent secondary conditions in people with SCI.
      SPONSORSHIP: This study was funded by the Alberta Paraplegic Foundation and the
      Glenrose Rehabilitation Hospital Foundation.

PMID- 17003773
TI  - A comparison of dual energy X-ray absorptiometry of the hip and accuDEXA of the
      finger for the diagnosis of osteoporosis in men on androgen deprivation therapy
      for advanced prostate cancer.
AB  - Dual energy X-ray absorptiometry (DEXA) of the hip or spine has been shown to be
      an effective screening tool for osteoporosis in men undergoing androgen
      deprivation therapy (ADT) for advanced carcinoma of the prostate. A less
      expensive alternative to DEXA is the use of peripheral scanners, such as
      accuDEXA, which measures bone mineral density (BMD) the finger. In this paper, we
      reviewed 59 patients on ADT who underwent both accuDEXA scan of the non-dominant
      hand and DEXA scan of the hip. The mean T-scores calculated by the two techniques
      were similar; however, the individual T-scores correlated poorly with each other.
      We conclude that men who require ADT for prostate cancer should undergo standard
      DEXA of the hip for osteoporosis screening.

PMID- 17003774
TI  - Androgen induces expression of the multidrug resistance protein gene MRP4 in
      prostate cancer cells.
AB  - Multidrug resistance-associated proteins (MRPs) may mediate multidrug resistance
      in tumor cells. Using a gene array analysis, we have identified MRP4 as an
      androgen receptor (AR)-regulated gene. Dihydrotestosterone induced MRP4
      expression in both androgen-dependent and -independent LNCaP cells, whereas there
      was little detectable expression in PC-3 or normal prostate epithelial cells.
      Disruption of MRP4 expression renders LNCaP cells more sensitive to the cytotoxic
      effects of methotrexate but not etoposide. Analysis of human tissues showed
      detectable MRP4 expression only in metastatic prostate cancer. These results
      suggest that AR induction of MRP4 mediates resistance of PC cells to nucleotide
      based chemotherapeutic drugs.

PMID- 17003775
TI  - Prostate-specific antigen adjusted for total prostatic tumor volume as a
      predictor for outcome after radical prostatectomy.
AB  - The aim of this study was to investigate the potential prognostic value of
      preoperative serum prostate-specific antigen levels adjusted for total tumor
      volume (PSA-TTV density) for outcome following radical prostatectomy for prostate
      cancer by retrospective review in 268 patients. Lower PSA-TTV density was not
      only associated with a significantly higher risk for biological failure (bF),
      systemic failure and cancer death but also an independent predictor for bF
      (hazard ratio, 6.3). Therefore, these data suggest that there are subsets of
      prostate cancer with lower PSA secretion levels, and this phenotype is associated
      with a higher risk of failure after surgery.

PMID- 17003777
TI  - Maternal hemoglobin concentration during pregnancy and risk of infant leukaemia:
      a children's oncology group study.
AB  - In contrast to the positive association found in three studies between maternal
      anaemia during pregnancy and childhood leukaemia, no such association was found
      in infant leukaemia (odds ratio 0.85, 95% confidence interval 0.53-1.37).

PMID- 17003776
TI  - 11q13 amplification status and human papillomavirus in relation to p16 expression
      defines two distinct etiologies of head and neck tumours.
AB  - Two distinct etiologies of head and neck squamous cell carcinoma (HNSCC) have
      been proposed, DNA damage owing to tobacco and alcohol exposure and human
      papillomavirus (HPV) oncogene-mediated transformation. Common genetic alterations
      in HNSCC include TP53 mutations, 11q13 amplification (amp) and CDKN2A/p16
      mutations or promoter methlyation. However, in HPV+ HNSCC it is frequent to
      observe wild-type TP53 and expression of p16. The relationship of this unusual
      pattern with 11q13 amp has not been tested. In a retrospective study on 125 HNSCC
      patients, only 17% (five out of 30) of HPV+ vs 44% (39 out of 89) of HPV -
      tumours expressed 11q13 amp (adjusted odds ratio (OR)=0.2, 95% confidence
      interval (CI)=0.1-0.6). A subpopulation of tumours (n=69) were classified
      according to the three molecular markers, TP53, p16 and 11q13 amp. In addition to
      wild-type TP53, and p16 expression, HPV+ tumours were more likely not to be
      amplified at 11q13 (OR=6.5, 95% CI=1.8-23.9). As HPV+ HNSCC lack the genetic
      alterations which are common in other tumours, we hypothesise that HPV infection
      may represent an early event in the HNSCC carcinogenic process, thus suggesting a
      distinct molecular pathway.

PMID- 17003778
TI  - The longitudinal relationship between circulating concentrations of C-reactive
      protein, interleukin-6 and interleukin-10 in patients undergoing resection for
      renal cancer.
AB  - The systemic inflammatory response, as evidenced by elevated circulating
      concentrations of C-reactive protein, is a stage-independent prognostic factor in
      patients undergoing curative nephrectomy for localised renal cancer. However, it
      is not clear whether the systemic inflammatory response arises from the tumour
      per se or as a result of an impaired immune cytokine response. The aim of the
      present study was to examine C-reactive protein, interleukin-6 and interleukin-10
      concentrations before and following curative resection of renal cancer. Sixty
      four patients with malignant renal disease and 12 with benign disease, undergoing
      resection were studied. Preoperatively, a blood sample was collected for routine
      laboratory analysis with a further sample stored before analysis of interleukin-6
      and interleukin-10 using an enzyme-linked immunosorbent assay (ELISA) technique.
      The blood sampling procedure and analyses were repeated at approximately 3 months
      following resection. Circulating concentrations of both interleukin-6 and
      interleukin (P< or =0.01) were higher and a greater proportion were elevated
      (P<0.05) in malignant compared with benign disease. The renal cancer patients
      were grouped according to whether they had evidence of a systemic inflammatory
      response. In the inflammatory group T stage was higher (P<0.01), both interleukin
      6 and interleukin-10 concentrations were higher (P<0.001) and elevated (P<0.10)
      compared with the non-inflammatory group. Tumour volume was weakly correlated
      with C-reactive protein (r(2)=0.20, P=0.002), interleukin-6 (r(2)=0.20, P=0.002)
      and interleukin-10 (r(2)=0.24, P=0.001). Following nephrectomy the proportion of
      patients with elevated C-reactive protein, interleukin-6 and interleukin-10
      concentrations did not alter significantly. An elevated preoperative C-reactive
      protein was associated with increased tumour stage, interleukin-6 and interleukin
      10 concentrations. However, resection of the primary tumour did not appear to be
      associated with significant normalisation of circulating concentrations of C
      reactive protein, interleukin-6 or interleukin-10. Therefore, the presence of
      systemic inflammatory response is unlikely to be solely be determined by the
      tumour itself, but may be as a result of an impaired immune cytokine response in
      patients with renal cancer.

PMID- 17003779
TI  - Family history and risk of lung cancer: age-at-diagnosis in cases and first
      degree relatives.
AB  - To investigate the little known risk of lung cancer at an early age when a first
      degree relative has had such a diagnosis, 579 incident cases and 1157 population
      controls were studied in Liverpool between 1998 and 2004 using standardised
      questionnaires covering demography and lifestyle. A history of lung cancer in
      first-degree relatives was associated with a significantly increased risk in the
      proband where in both individuals the cancers were diagnosed before the age of 60
      years (odds ratio (OR)=4.89; 95% confidence interval (CI): 1.47-16.25). A
      significantly elevated risk of lung cancer was also observed in association with
      a relative affected before the age of 60 years, regardless of age-at-onset of the
      disease (OR=2.08; 95% CI: 1.20-3.59). This finding is strongly consistent with a
      genetic component in early-onset lung cancer risk.

PMID- 17003780
TI  - Prognostic relevance of Tiam1 protein expression in prostate carcinomas.
AB  - The Rac-specific guanine nucleotide exchange factor, Tiam1, plays a major role in
      oncogenicity, tumour invasion and metastasis but its usefulness as a prognostic
      marker in human cancer has not been tested yet. In the present study, Tiam1
      expression was analysed in benign secretory epithelium, pre-neoplastic high-grade
      prostatic intraepithelium neoplasia (HG-PIN) and prostate carcinomas of 60 R0
      resected radical prostatectomy specimens by semiquantitative
      immunohistochemistry. Tiam1 proved significantly overexpressed in both HG-PIN
      (P<0.001) and prostate carcinomas (P<0.001) when compared to benign secretory
      epithelium. Strong Tiam1 overexpression (i.e. > or =3.5-fold) in prostate
      carcinomas relative to the respective benign prostatic epithelium was
      statistically significantly associated with disease recurrence (P=0.016), the
      presence of lymph vessel invasion (P=0.031) and high Gleason scores (GS) (i.e. >
      or =7) (P=0.044). Univariate analysis showed a statistically significant
      association of strong Tiam1 overexpression with decreased disease-free survival
      (DFS) (P=0.03). This prognostic effect of strong Tiam1 overexpression remained
      significant in multivariate analysis including preoperative prostate-specific
      antigen levels, pT stage, and GS (relative risk= 3.75, 95% confidence
      interval=1.06-13.16; P=0.04). Together, our data suggest that strong Tiam1
      overexpression relative to the corresponding benign epithelial cells is a new and
      independent predictor of decreased DFS for patients with prostate cancer.

PMID- 17003781
TI  - Altered sirtuin expression is associated with node-positive breast cancer.
AB  - Sirtuins are genes implicated in cellular and organismal ageing. Consequently,
      they are speculated to be involved in diseases of ageing including cancer.
      Various cancers with widely differing prognosis have been shown to have differing
      and characteristic expression of these genes; however, the relationship between
      sirtuin expression and cancer progression is unclear. In order to correlate
      cancer progression and sirtuin expression, we have assessed sirtuin expression as
      a function of primary cell ageing and compared sirtuin expression in normal,
      'nonmalignant' breast biopsies to breast cancer biopsies using real-time
      polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly
      increased in breast cancer (P<0.0001). Increased levels of SIRT3 and SIRT7
      transcription were also associated with node-positive breast cancer (P<0.05 and
      P<0.0001, respectively). This study has demonstrated differential sirtuin
      expression between nonmalignant and malignant breast tissue, with consequent
      diagnostic and therapeutic implications.

PMID- 17003782
TI  - Case-control, kin-cohort and meta-analyses provide no support for STK15 F31I as a
      low penetrance colorectal cancer allele.
AB  - Recently, homozygosity for T91A single-nucleotide polymorphism (SNP) in the
      serine/threonine kinase (STK15) gene, which generates the substitution F31I has
      been proposed to increase the risk of a number of tumours including colorectal
      cancer (CRC). To further evaluate the relationship between STK15 F31I and risk of
      CRC, we genotyped 2558 CRC cases and 2680 controls for this polymorphism. We
      found no evidence that homozygosity for the STK15 31I genotype confers an
      increased risk of CRC (odds ratio=0.95, 95% confidence interval (CI): 0.74-1.24).
      We also conducted a kin-cohort analysis to assess risk among first-degree
      relatives of the CRC cases. The hazard ratio for I/I homozygotes compared to F/F
      homozygotes was 1.65 (95% CI: 0.39-3.17). A meta-analysis of our case-control
      data and three previous studies also provided no evidence of an elevated risk of
      CRC associated with homozygosity. These data provide no support for the
      hypothesis that sequence variation in STK15 defined by SNP F31I per se confers an
      elevated risk of CRC.

PMID- 17003783
TI  - Are microRNAs located in genomic regions associated with cancer?
AB  - We report on the location of 283 miRNAs in the human genome in relation to copy
      number changes in three distinct types of tumours: prostate, bladder and colon.
      In prostate and colon tumours, we find miRNAs over-represented in regions with
      copy number gain and under-represented in regions with copy number loss.
      Surprisingly this pattern appears to be reversed in bladder cancer. We compared
      our miRNA copy number data to published miRNA expression data; unexpectedly, we
      did not find a statistically significant relationship between miRNA copy number
      and expression level. This suggests that miRNA expression is regulated through
      different mechanisms than mRNA expression.

PMID- 17003784
TI  - A model of the natural history of screen-detected prostate cancer.

PMID- 17003787
TI  - Evidence-based dentistry--a challenge for dental education.

PMID- 17003789
TI  - Topical fluoride guidance.

PMID- 17003785
TI  - Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated
      PDGFR-beta and VEGF expression, decrease in interstitial fluid pressure and
      improvement of oxygenation.
AB  - Elevated intratumoral interstitial fluid pressure (IFP) and tumour hypoxia are
      independent predictive factors for poor survival and poor treatment response in
      cancer patients. However, the relationship between IFP and tumour hypoxia has not
      yet been clearly established. Preclinical studies have shown that lowering IFP
      improves treatment response to cytotoxic therapy. Interstitial fluid pressure can
      be reduced by inhibition of phosphorylated platelet-derived growth factor
      receptor-beta (p-PDGFR-beta), a tyrosine kinase receptor frequently overexpressed
      in cancer stroma, and/or by inhibition of VEGF, a growth factor commonly
      overexpressed in tumours overexpressing p-PDGFR-beta. We hypothesised that
      Imatinib, a specific PDGFR-beta inhibitor will, in addition to p-PDGFR-beta
      inhibition, downregulate VEGF, decrease IFP and improve tumour oxygenation. A549
      human lung adenocarcinoma xenografts overexpressing PDGFR-beta were grown in nude
      mice. Tumour-bearing animals were randomised to control and treatment groups
      (Imatinib 50 mg kg(-1) via gavage for 4 days). Interstitial fluid pressure was
      measured in both groups before and after treatment. EF5, a hypoxia marker, was
      administered 3 h before being killed. Tumours were sectioned and stained for p
      PDGFR-beta, VEGF and EF5 binding. Stained sections were viewed with a
      fluorescence microscope and image analysis was performed. Imatinib treatment
      resulted in significant reduction of p-PDGFR-beta, VEGF and IFP. Tumour
      oxygenation was also significantly improved. This study shows that p-PDGFR-beta
      overexpressing tumours can be effectively treated with Imatinib to decrease
      tumour IFP. Importantly, this is the first study demonstrating that Imatinib
      treatment improves tumour oxygenation and downregulates tumour VEGF expression.

PMID- 17003790
TI  - Fluoride varnish should be part of caries prevention programmes.

PMID- 17003791
TI  - Adjunctive antibiotics in the treatment of generalized aggressive periodontitis.

PMID- 17003792
TI  - Professional flossing is effective in reducing interproximal caries risk in
      children who have low fluoride exposures.

PMID- 17003793
TI  - Little value in providing professional mechanical plaque removal without oral
      hygiene instruction.

PMID- 17003794
TI  - Self-reporting measures for periodontal disease.

PMID- 17003795
TI  - Preoperative clindamycin prophylaxis does not prevent postoperative infections in
      endodontic surgery.

PMID- 17003796
TI  - Dentures and their impact on social and sexual activities.

PMID- 17003797
TI  - Oral lichenoid lesions and amalgam fillings.

PMID- 17003798
TI  - Just a little magic.

PMID- 17003799
TI  - CAL programs in orthodontics elicit positive responses from students.

PMID- 17003800
TI  - Tongue scrapers may reduce halitosis in adults.

PMID- 17003801
TI  - Strong association between areca nut use and oral submucous fibrosis.

PMID- 17003802
TI  - To screen or not to screen? Is it worth it for oral cancer?

PMID- 17003803
TI  - Study design V. Case-control studies.
AB  - Previously in this series I have given an overview of the main types of study
      design and the techniques used to minimise biased results. In this article I
      describe more fully case control studies, their uses, advantages and limitations.

PMID- 17003807
TI  - A new approach to assessing the health benefit from obesity interventions in
      children and adolescents: the assessing cost-effectiveness in obesity project.
AB  - OBJECTIVE: To report on a new modelling approach developed for the assessing cost
      effectiveness in obesity (ACE-Obesity) project and the likely population health
      benefit and strength of evidence for 13 potential obesity prevention
      interventions in children and adolescents in Australia. METHODS: We used the best
      available evidence, including evidence from non-traditional epidemiological study
      designs, to determine the health benefits as body mass index (BMI) units saved
      and disability-adjusted life years (DALYs) saved. We developed new methods to
      model the impact of behaviours on BMI post-intervention where this was not
      measured and the impacts on DALYs over the child's lifetime (on the assumption
      that changes in BMI were maintained into adulthood). A working group of
      stakeholders provided input into decisions on the selection of interventions, the
      assumptions for modelling and the strength of the evidence. RESULTS: The likely
      health benefit varied considerably, as did the strength of the evidence from
      which that health benefit was calculated. The greatest health benefit is likely
      to be achieved by the 'Reduction of TV advertising of high fat and/or high sugar
      foods and drinks to children', 'Laparoscopic adjustable gastric banding' and the
      'multi-faceted school-based programme with an active physical education
      component' interventions. CONCLUSIONS: The use of consistent methods and common
      health outcome measures enables valid comparison of the potential impact of
      interventions, but comparisons must take into account the strength of the
      evidence used. Other considerations, including cost-effectiveness and
      acceptability to stakeholders, will be presented in future ACE-Obesity papers.
      Information gaps identified include the need for new and more effective
      initiatives for the prevention of overweight and obesity and for better
      evaluations of public health interventions.

PMID- 17003809
TI  - SLITRK1 mutations in trichotillomania.

PMID- 17003810
TI  - Human food preferences are associated with a 5-HT(2A) serotonergic receptor
      polymorphism.

PMID- 17003811
TI  - Impact of obesity on arteriovenous fistula outcomes in dialysis patients.
AB  - Fistula use for dialysis is less frequent among obese than non-obese patients.
      This discrepancy may be due to a lower rate of fistula placement in obese
      patients, a higher primary failure rate (fistulas that are never usable for
      dialysis), or a higher secondary failure rate (fistulas that fail after being
      used successfully for dialysis). Using a prospective, computerized vascular
      access database, we identified all patients receiving a first fistula or graft at
      our institution during a 2-year period. The access outcomes were compared between
      obese (body mass index (BMI) >or=30 kg/m2) and non-obese (BMI<30 kg/m2) patients.
      Fistula placement was equally likely between obese and non-obese patients (47.4
      vs 47.1%). The primary failure rate of fistulas was similar in both groups (46 vs
      41%, P=0.45). Among those fistulas that were usable for dialysis, the secondary
      survival was worse in obese patients (hazard ratio 2.74; 95% confidence interval
      (CI), 1.48-7.90; P=0.004). Secondary fistula survival in obese vs non-obese
      patients was 68 vs 92% at 1 year, 59 vs 78% at 2 years, and 47 vs 70% at 3 years.
      On multiple variable survival analysis with age, sex, race, diabetes, coronary
      artery disease, peripheral vascular disease, fistula location, surgeon, and
      obesity in the model, obesity was the only significant factor predicting
      secondary fistula failure (hazards ratio 2.93; 95% CI, 1.44-5.93; P=0.004). In
      conclusion, long-term fistula survival is worse in obese than non-obese patients,
      owing to a higher secondary failure rate.

PMID- 17003812
TI  - Renal and vascular function in women with previous preeclampsia: a comparison of
      low- and high-degree proteinuria.
AB  - The degree of proteinuria during preeclampsia has been considered to be a marker
      of severity of the disease and of endothelial dysfunction. The aim of the study
      was to assess whether the degree of proteinuria in preeclamptic pregnancy is
      related to impairment of vascular dilatation and/or kidney function years after
      the index pregnancy. Thirty women with a history of severe preeclampsia divided
      into low (n=8, dU-prot <5 g/day) and high (n=22, dU-prot >/=5 g/day) proteinuric
      groups and 21 women with previous normotensive pregnancy were studied 5-6 years
      after index pregnancy. Renal function and blood pressure were assessed together
      with venous occlusion plethysmography, where changes in brachial artery blood
      flow, induced by intra-arterial infusions of an endothelium-independent (sodium
      nitroprusside) and an endothelium-dependent (acetylcholine) vasodilator, were
      measured. The results showed similar renal function in all groups. There was no
      difference in vasodilation between preeclamptic groups and controls or
      correlation between degree of proteinuria during index pregnancy and present
      vasodilation. We conclude that the degree of proteinuria during preeclampsia does
      not predict vascular dilatation or renal function 5-6 years after preeclamptic
      pregnancy.

PMID- 17003813
TI  - The role of heme oxygenase 1 in rapamycin-induced renal dysfunction after
      ischemia and reperfusion injury.
AB  - Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure
      in native and transplanted kidneys. In the transplantation field,
      immunosuppressive drugs may play an additional role in acute graft dysfunction.
      Rapamycin may impair renal regeneration post IRI. Heme oxygenase 1 (HO-1) is a
      protective gene with anti-inflammatory and anti-apoptotic actions. We
      investigated whether HO-1 played a role in rapamycin-induced renal dysfunction in
      an established model of IRI. Rapamycin (3 mg/kg) was administered to mice before
      being subjected to 45 min of ischemia. Animals subjected to IRI presented with
      impaired renal function that peaked at 24 h (2.05+/-0.23 mg/dl), decreasing
      thereafter. Treatment with rapamycin caused even more renal dysfunctions (2.30+/
      0.33 mg/dl), sustained up to 120 h after reperfusion (1.54+/-0.4 mg/dl), when
      compared to the control (0.63+/-0.09 mg/dl, P<0.05). Rapamycin delayed tubular
      regeneration that was normally higher in the control group at day 5 (68.53+/-2.30
      vs 43.63+/-3.11%, P<0.05). HO-1 was markedly upregulated after IRI and its
      expression was even enhanced by rapamycin (1.32-fold). However, prior induction
      of HO-1 by cobalt protoporphyrin improved the renal dysfunction imposed by
      rapamycin, mostly at later time points. These results demonstrated that rapamycin
      used in ischemic-injured organs could also negatively affect post-transplantation
      recovery. Modulation of HO-1 expression may represent a feasible approach to
      limit rapamycin acute toxicity.

PMID- 17003814
TI  - Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar
      or low-osmolar contrast media.
AB  - We compared the Swedish Coronary Angiography and Angioplasty Registry with the
      Swedish 'Hospital Discharge Register' to assess contrast media (CM)-induced renal
      failure. Hospitals used only one type CM. From 2000 to 2003, iodixanol (iso
      osmolar) was used in 45 485 patients, ioxaglate (low osmolar) in 12 440 subjects.
      To include the earlier used CM iohexol (low osmolar), analysis extended back to
      1990 (86 334 patients). Incidence of clinically significant renal failure was
      greatest for patients receiving the iso-osmolar CM iodixanol (1.7%). Ioxaglate
      treated patients had a significantly lower renal failure incidence (0.8%,
      P<0.001). The odds ratio for iodixanol-treated patients was significantly higher
      than for ioxaglate (1 vs 0.48, P<0.001). In subsets of either diabetic patients
      or patients with previous renal failure, odds ratios for renal failure remained
      greater in the iodixanol groups (P<0.01). Hospitals switching CM to iodixanol
      experienced a doubling in clinically significant renal failure after cardiac
      procedures. Dialysis was required in 0.2% of patients receiving iodixanol, which
      was significantly higher (P<0.01) than for ioxaglate-treated patients (0.1%).
      Iohexol-treated patients had a similar low risk for developing clinically
      significant renal failure (0.9%) as ioxaglate. In conclusion, risk of developing
      renal failure and required dialysis after coronary procedures is higher when
      patients received iodixanol than ioxaglate or iohexol.

PMID- 17003815
TI  - Vasopressin administration facilitates fluid removal during hemodialysis.
AB  - Inadequate secretion of vasopressin during fluid removal by hemodialysis may
      contribute to the cardiovascular instability that complicates this therapy and
      administration of exogenous hormone, by supporting arterial pressure, may
      facilitate volume removal. To test this, we measured plasma vasopressin in
      patients with end-stage renal disease (ESRD) during hemodialysis and found that
      despite significant fluid removal, plasma vasopressin concentration did not
      increase. We further found that ESRD did not alter the endogenous removal rate of
      plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a
      randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients,
      we examined the effect of a constant infusion of a non-pressor dose of
      vasopressin on the arterial pressure response during a hemodialysis in which the
      target fluid loss was increased by 0.5 kg over the baseline prescription. We
      found that arterial pressure was more stable in the patients receiving
      vasopressin and that while only one patient (9%) in the vasopressin group had a
      symptomatic hypotensive episode, 64% of the patients receiving placebo had such
      an episode (P=0.024). Moreover, increased fluid removal was achieved only in the
      vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of
      non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular
      stability during hemodialysis and allows increased removal of excess
      extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced
      fluid removal is a likely contributor to the intradialytic hypotension that
      limits fluid removal.

PMID- 17003816
TI  - Increasing incidence of proteinuria and declining incidence of end-stage renal
      disease in diabetic Pima Indians.
AB  - The introduction of more efficacious treatments for diabetic kidney disease may
      slow its progression, but evidence for their effectiveness in populations is
      sparse. We examined trends in the incidence of clinical proteinuria, defined as a
      urinary protein-to-creatinine ratio >0.5 g/g, and diabetic end-stage renal
      disease (ESRD), defined as death from diabetic nephropathy or onset of dialysis,
      in Pima Indians with type 2 diabetes between 1967 and 2002. The study included
      2189 diabetic subjects >/=25 years old. During follow-up, 366 incident cases of
      proteinuria occurred in the subset of 1715 subjects without proteinuria at
      baseline. The age-sex-adjusted incidence rate of proteinuria increased from 24.3
      cases/1000 person-years (pyrs) (95% confidence interval (CI) 18.7-30.0) in 1967
      1978 to 35.4 cases/1000 pyrs (95% CI 28.1-42.8) in 1979-1990 and 38.9 cases/1000
      pyrs (95% CI 31.2-46.5) in 1991-2002 (P(trend)<0.0002). In each period, the age
      sex-adjusted incidence of proteinuria increased with diabetes duration, but
      diabetes duration-specific incidence was stable throughout the study period
      (P=0.8). The age-sex-adjusted incidence of ESRD increased between 1967 and 1990
      and declined thereafter. The incidence of proteinuria increased over 36 years in
      Pima Indians as the proportion of people with diabetes of long duration
      increased. On the other hand, the incidence of ESRD declined after 1990,
      coinciding with improved control of blood pressure, hyperglycemia, and perhaps
      other risk factors.

PMID- 17003817
TI  - Grading evidence and recommendations for clinical practice guidelines in
      nephrology. A position statement from Kidney Disease: Improving Global Outcomes
      (KDIGO).
AB  - Considerable variation in grading systems used to rate the strength of guideline
      recommendations and the quality of the supporting evidence in Nephrology
      highlights the need for a uniform, internationally accepted, rigorous system. In
      2004, Kidney Disease: Improving Global Outcomes (KDIGO) commissioned a methods
      expert group to recommend an approach for grading in future nephrology
      guidelines. This position statement by KDIGO recommends adopting the Grades of
      Recommendation Assessment, Development, and Evaluation (GRADE) approach for the
      grading of evidence and guidelines on interventions. The GRADE approach appraises
      systematic reviews of the benefits and harms of an intervention to determine its
      net health benefit. The system considers the design, quality, and quantity of
      studies as well as the consistency and directness of findings when grading the
      quality of evidence. The strength of the recommendation builds on the quality of
      the evidence and additional considerations including costs. Adaptations of the
      GRADE approach are presented to address some issues pertinent to the field of
      nephrology, including (1) the need to extrapolate from studies performed
      predominantly in patients without kidney disease, and (2) the need to use
      qualitative summaries of effects when it is not feasible to quantitatively
      summarize them. Further refinement of the system will be required for grading of
      evidence on questions other than those related to intervention effects, such as
      diagnostic accuracy and prognosis.

PMID- 17003818
TI  - Kinin-dependent hypersensitivity reactions in hemodialysis: metabolic and genetic
      factors.
AB  - Although the association of angiotensin I-converting enzyme inhibitors (ACEis)
      with a negatively charged membrane is thought to be responsible for
      hypersensitivity reactions (HSRs) during hemodialysis, we hypothesize that these
      complications are due to changes in plasma aminopeptidase P (APP) activity and
      genotype. To test this hypothesis, we measured plasma APP activity in 14 patients
      who suffered HSR (HSR+) while dialyzed with an AN69 membrane and simultaneously
      treated with an ACEi. APP activity was also studied in a control group (n=39)
      dialyzed under the same conditions, but who did not suffer any side effect (HSR
      ). We found significantly decreased plasma APP activity (P=0.013) in HSR+
      subjects as well as altered degradation of endogenous des-Arginine(9)-bradykinin,
      with a significantly lower beta value (P<0.001). The same analytical approach was
      taken in 171 relatives of HSR+ patients. Variance component analysis suggested
      that genetic differences may explain 61% of the phenotypic variability of plasma
      APP activity (P<0.001) and the kinetic parameters that characterized kinin
      degradation. We also showed that the C-2399A single-nucleotide polymorphism at
      the XPNPEP2 locus was a significant predictor of APP activity in the 39 HSR-
      controls (P=0.029). Furthermore, a recessive genetic model for the A allele
      disclosed a significant difference in mean APP activity by genotype (P<0.001).
      Finally, our study defined the nonspecific inhibition of recombinant APP by some
      ACEis. In conclusion, this paper highlights the complexity of HSR in
      hemodialysis, suggesting, as with angioedema, that these rare, but life
      threatening adverse events are governed by several metabolic and genetic factors.

PMID- 17003819
TI  - Cytokine cooperation in renal tubular cell injury: the role of TWEAK.
AB  - Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK, TNFSF12) is a
      member of the TNF superfamily. TWEAK activates the Fn14 receptor, and may
      regulate apoptosis, proliferation, and inflammation, processes that play a
      significant role in pathological conditions. However, there is little information
      on the function and regulation of this system in the kidney. Therefore, TWEAK and
      Fn14 expression were studied in cultured murine tubular epithelial MCT cells and
      in mice in vivo. The effect of TWEAK on cell death was determined. We found that
      TWEAK and Fn14 expression was increased in experimental acute renal failure
      induced by folic acid. Cultured tubular cells express both TWEAK and the Fn14
      receptor. TWEAK did not induce cell death in non-stimulated tubular cells.
      However, in cells costimulated with TNFalpha/interferon-gamma, TWEAK induced
      apoptosis through the activation of the Fn14 receptor. Apoptosis was associated
      with activation of caspase-8, caspase-9, and caspase-3, Bid cleavage, and
      evidence of mitochondrial injury. There was no evidence of endoplasmic reticulum
      stress. A pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp prevented TWEAK
      induced apoptosis, but it sensitized cells to necrosis via generation of reactive
      oxygen species. In conclusion, cooperation between inflammatory cytokines results
      in tubular cell death. TWEAK and Fn14 may play a role in renal tubular cell
      injury.

PMID- 17003820
TI  - Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and
      predictive factors.
AB  - Tuberous sclerosis complex is a genetic disorder characterized by hamartomatous
      lesions in multiple organs, frequently involving the kidney. We conducted a
      retrospective review of the clinical and radiographic records of 167 patients
      with tuberous sclerosis to determine the frequency of renal disease, the
      likelihood of significant renal morbidity, and the effects of genotype (TSC1 vs
      TSC2) and gender on renal phenotype. Renal lesions were seen in 57.5% of
      patients. Of these, angiomyolipoma (AML) occurred in 85.4%, cysts in 44.8%, and
      renal cell carcinoma in 4.2%. Both AML and cysts were significantly more common
      and more numerous in TSC2 than in TSC1. AML was significantly more common in
      female than in male patients, but cysts showed no correlation with gender. Eleven
      patients developed renal abnormalities during their care in this practice at an
      average age of onset of 11.3 years (range 3.8-23 years). The frequency and number
      of renal lesions were positively correlated with age. Interventions, including
      arterial embolization and nephrectomy, were performed in 11 (6.6%) patients.
      Among female patients with lymphangioleiomyomatosis, renal AML was universally
      present. Our findings confirm a high rate of renal involvement; a low rate of
      serious complications; significant associations between renal involvement,
      genotype, and gender; and a significant association between renal and pulmonary
      involvement in female patients.

PMID- 17003821
TI  - Treatment of post-dialytic orthostatic hypotension with an inflatable abdominal
      band in hemodialysis patients.
AB  - The purpose of this study was to ascertain whether abdominal compression with an
      inflatable abdominal band, a device we developed, improved post-dialytic
      orthostatic hypotension (OH) in hemodialysis (HD) patients. Twenty-five chronic
      HD patients with intractable post-dialytic OH were recruited. Post-HD changes in
      systolic blood pressure (DeltaSBP) in the supine and standing positions were
      compared in the patients, measured with or without the use of the band. The study
      showed DeltaSBP after HD without the band was significantly greater than that
      measured before HD (-36.1+/-18.2 vs -13.1+/-16.8 mm Hg; P<0.0001). DeltaSBP after
      HD with the band was reduced significantly in comparison to DeltaSBP after HD
      without the band (-19.4+/-21.2 vs -36.1+/-18.2 mm Hg; P<0.002). Use of the band
      did not cause an elevation in SBP in the supine position (149.0+/-29.6 vs 155.4+/
      25.7 mm Hg); however, it did increase SBP upon standing (129.6+/-27.3 vs 117.2+/
      22.6 mm Hg; P<0.05). Eight patients in whom an increase in SBP of 25 mm Hg or
      more was achieved with the band were classified as responders. Ejection fraction
      was significantly higher (76.4+/-11.1 vs 61.9+/-13.6%; P<0.02) and atrial
      natriuretic peptide concentration significantly lower (27.9+/-22.0 vs 68.9+/-47.5
      pg/ml; P<0.02) in responders than in non-responders. We conclude that the
      abdominal band was effective for overcoming post-dialytic OH, without elevating
      supine SBP in some patients.

PMID- 17003822
TI  - Proteinuria and reduced kidney function in living kidney donors: A systematic
      review, meta-analysis, and meta-regression.
AB  - We reviewed any study where 10 or more healthy adults donated a kidney, and
      proteinuria, or glomerular filtration rate (GFR) was assessed at least 1 year
      later. Bibliographic databases were searched until November 2005. 31 primary
      authors provided additional information. Forty-eight studies from 27 countries
      followed a total of 5048 donors. An average of 7 years after donation (range 1-25
      years), the average 24 h urine protein was 154 mg/day and the average GFR was 86
      ml/min. In eight studies which reported GFR in categories, 12% of donors
      developed a GFR between 30 and 59 ml/min (range 0-28%), and 0.2% a GFR less than
      30 ml/min (range 0-2.2%). In controlled studies urinary protein was higher in
      donors and became more pronounced with time (three studies totaling 59 controls
      and 129 donors; controls 83 mg/day, donors 147 mg/day, weighted mean difference
      66 mg/day, 95% confidence interval (CI) 24-108). An initial decrement in GFR
      after donation was not accompanied by accelerated losses over that anticipated
      with normal aging (six studies totaling 189 controls and 239 donors; controls 96
      ml/min, donors 84 ml/min, weighted mean difference 10 ml/min, 95% CI 6-15;
      difference not associated with time after donation (P=0.2)). Kidney donation
      results in small increases in urinary protein. An initial decrement in GFR is not
      followed by accelerated losses over a subsequent 15 years. Future studies will
      provide better estimates, and identify those donors at least risk of long-term
      morbidity.

PMID- 17003823
TI  - Ifosfamide metabolites CAA, 4-OH-Ifo and Ifo-mustard reduce apical phosphate
      transport by changing NaPi-IIa in OK cells.
AB  - Renal Fanconi syndrome occurs in about 1-5% of all children treated with
      Ifosfamide (Ifo) and impairment of renal phosphate reabsorption in about 20-30%
      of them. Pathophysiological mechanisms of Ifo-induced nephropathy are ill
      defined. The aim has been to investigate whether Ifo metabolites affect the type
      IIa sodium-dependent phosphate transporter (NaPi-IIa) in viable opossum kidney
      cells. Ifo did not influence viability of cells or NaPi-IIa-mediated transport up
      to 1 mM/24 h. Incubation of confluent cells with chloroacetaldehyde (CAA) and 4
      hydroperoxyIfosfamide (4-OH-Ifo) led to cell death by necrosis in a concentration
      dependent manner. At low concentrations (50-100 microM/24 h), cell viability was
      normal but apical phosphate transport, NaPi-IIa protein, and -mRNA expression
      were significantly reduced. Coincubation with sodium-2-mercaptoethanesulfonate
      (MESNA) prevented the inhibitory action of CAA but not of 4-OH-Ifo; DiMESNA had
      no effect. Incubation with Ifosfamide-mustard (Ifo-mustard) did alter cell
      viability at concentrations above 500 microM/24 h. At lower concentrations (50
      100 microM/24 h), it led to significant reduction in phosphate transport, NaPi
      IIa protein, and mRNA expression. MESNA did not block these effects. The effect
      of Ifo-mustard was due to internalization of NaPi-IIa. Cyclophosphamide-mustard
      (CyP-mustard) did not have any influence on cell survival up to 1000 microM, but
      the inhibitory effect on phosphate transport and on NaPi-IIa protein was the same
      as found after Ifo-mustard. In conclusion, CAA, 4-OH-Ifo, and Ifo- and CyP
      mustard are able to inhibit sodium-dependent phosphate cotransport in viable
      opossum kidney cells. The Ifo-mustard effect took place via internalization and
      reduction of de novo synthesis of NaPi-IIa. Therefore, it is possible that Ifo
      mustard plays an important role in pathogenesis of Ifo-induced nephropathy.

PMID- 17003824
TI  - Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal
      chronic unilateral ureteral obstruction.
AB  - Congenital obstructive nephropathy is a major cause of renal insufficiency in
      children. Osteopontin (OPN) is a phosphoprotein produced by the kidney that
      mediates cell adhesion and migration. We investigated the role of OPN in the
      renal response to unilateral ureteral obstruction (UUO) in neonatal mice. OPN
      null mutant (-/-) and wild-type (+/+) mice were subjected to sham operation or
      UUO within the first 2 days of life. At 7 and 21 days of age, fibroblasts
      (fibroblast-specific protein (FSP)-1), myofibroblasts (alpha-smooth muscle actin
      (SMA)), and macrophages (F4/80) were identified by immunohistochemical staining.
      Apoptotic cells were detected by terminal deoxy transferase uridine triphosphate
      nick end-labeling technique and interstitial collagen by Masson trichrome or
      picrosirius red stain. Compared to sham-operated or contralateral kidneys,
      obstructed kidneys showed increases in all parameters by 7 days, with further
      increases by 21 days. After 21 days UUO, there was an increase in tubular and
      interstitial apoptosis in OPN -/- mice as compared to +/+ animals (P<0.05).
      However, FSP-1- and alpha-SMA-positive cells and collagen in the obstructed
      kidney were decreased in OPN -/- compared to +/+ mice (P<0.05), whereas the
      interstitial macrophage population did not differ between groups. We conclude
      that OPN plays a significant role in the recruitment and activation of
      interstitial fibroblasts to myofibroblasts in the progression of interstitial
      fibrosis in the developing hydronephrotic kidney. However, OPN also suppresses
      apoptosis. Future approaches to limit the progression of obstructive nephropathy
      in the developing kidney will require targeting of specific renal compartments.

PMID- 17003825
TI  - A regulated system of living kidney sales.

PMID- 17003826
TI  - ISN and the 'new nephrology'.

PMID- 17003827
TI  - The benefits of renin-angiotensin blockade in hypertension are dependent on blood
      pressure lowering.

PMID- 17003828
TI  - 'Renal-dose' fenoldopam for early-stage renal dysfunction in critically ill
      patients.

PMID- 17003829
TI  - A prospective comparison of prednisone plus ciclosporin and prednisone alone in
      pediatric nephrotic syndrome.

PMID- 17003830
TI  - Intravenous vitamin C can improve anemia in erythropoietin-hyporesponsive
      hemodialysis patients.

PMID- 17003831
TI  - Does stenting prolong the patency of arteriovenous grafts after thrombectomy and
      angioplasty?

PMID- 17003832
TI  - Is living-donor kidney volume an independent determinant of post-transplantation
      graft performance?

PMID- 17003833
TI  - Mycophenolate mofetil versus sirolimus as an adjunct to calcineurin inhibition
      after renal transplantation.

PMID- 17003834
TI  - Outcomes of patients commencing peritoneal dialysis after failure of their renal
      allograft.

PMID- 17003835
TI  - Hypertension and antihypertensive treatment of diabetic nephropathy.
AB  - We are currently confronted with an epidemic of renal failure caused by diabetic
      nephropathy. It has become apparent that blood pressure is a major determinant of
      the risk of developing diabetic nephropathy; individuals with a genetic
      predisposition to hypertension are at increased risk of developing diabetes and
      diabetic nephropathy. Antihypertensive medication has an impact on development of
      diabetes; beyond blood-pressure lowering, the risk of diabetes is further reduced
      by blockade of the renin-angiotensin system (RAS). In experimental studies,
      blockade of the RAS in the pre-diabetic stage ameliorates the severity of
      subsequent diabetic nephropathy. Guidelines recommend a target blood pressure of
      130/80 mmHg for diabetic patients without proteinuria and some guidelines
      recommend a target of less than 125/175 mmHg for diabetic patients with
      proteinuria. Above a systolic blood pressure of approximately 110 mmHg, the risk
      of progression of diabetic nephropathy increases progressively with increasing
      blood pressure. Blood-pressure lowering and blockade of the RAS delays or
      prevents onset of microalbuminuria, slows worsening of microalbuminuria and
      attenuates progression of diabetic nephropathy, even in advanced stages. In
      addition to blood pressure, proteinuria is a treatment target and should be
      reduced to below 1 g/24 h.

PMID- 17003836
TI  - Renal Toll-like receptors: recent advances and implications for disease.
AB  - Toll-like receptors (TLRs) are proteins that recognize specific molecular
      patterns of pathogens. They can also interact with a variety of endogenous
      ligands. When stimulated, TLRs initiate a cascade of signaling events leading to
      the production of a myriad of cytokines and effector molecules. Early
      investigations extensively characterized TLRs on cells of the innate immune
      system. More recently, TLRs have been found to reside in organs such as the
      heart, lungs, intestines, liver and kidneys. The role of these TLRs is not fully
      understood and is the subject of intensive current research. The available
      information indicates that renal TLRs have the potential to interact with
      exogenous and endogenous ligands, thereby influencing kidney function in health
      and disease. Here, we present an overview of what is currently known about renal
      TLRs, and discuss the potential implications for further research and clinical
      practice.

PMID- 17003837
TI  - Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of
      hypertension.
AB  - Animal studies have shown that oxidative stress and renal tubulointerstitial
      inflammation are associated with, and have major roles in, the pathogenesis of
      hypertension. This view is supported by the observations that alleviation of
      oxidative stress and renal tubulointerstitial inflammation reduce arterial
      pressure in animal models. Conversely, hypertension has been shown to cause
      oxidative stress and inflammation in renal and cardiovascular tissues in
      experimental animals. Taken together, these observations indicate that oxidative
      stress, inflammation and arterial hypertension participate in a self-perpetuating
      cycle which, if not interrupted, can lead to progressive cardiovascular disease
      and renal complications. These events usually occur in an insidious and
      asymptomatic manner over an extended period following the onset of hypertension.
      Severe target organ injury can, however, occasionally occur precipitously in the
      course of malignant or accelerated hypertension. Given the high degree of
      heterogeneity of hypertensive disorders, the factor(s) initiating the vicious
      cycle described vary considerably in different forms of hypertension. For
      instance, oxidative stress in the kidney and vascular tissue is the primary
      mediator in the pathogenesis of angiotensin-induced, and perhaps lead-induced,
      hypertension. By contrast, increased arterial pressure is probably the initiating
      trigger in salt-sensitive hypertension. Although the initiating factor might vary
      between hypertensive disorders, according to the proposed model, the three
      components of the cycle eventually coalesce in all forms of hypertension.

PMID- 17003838
TI  - Acute renal failure associated with immune restoration inflammatory syndrome.
AB  - BACKGROUND: A 30-year-old HIV-infected woman presented with fever and abdominal
      pain 4 days after initiation of highly active antiretroviral therapy (HAART), and
      1 month after initiation of antimicrobial therapy for Mycobacterium tuberculosis
      infection. A diagnosis of immune restoration inflammatory syndrome (IRIS) was
      considered, and corticosteroids were started. Steroid therapy doses were
      progressively tapered, during which time the patient developed renal failure with
      enlarged kidneys. A renal biopsy showed acute interstitial nephritis. Extensive
      investigations failed to detect active infection. The efficacy of HAART was
      attested by increased CD4+ cell counts and undetectable viral replication.
      INVESTIGATIONS: Physical examination, plasma viral load and CD4+ cell count,
      abdominal and renal ultrasound, renal and peritoneal biopsies, renal and liver
      function, chest X-ray, and bronchoalveolar lavage culture. DIAGNOSIS: Acute renal
      failure secondary to IRIS. MANAGEMENT: Prednisone therapy.

PMID- 17003839
TI  - Cystatin B: mutation detection, alternative splicing and expression in
      progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients.
AB  - Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal
      recessive neurodegenerative disorder caused by mutations in the cystatin B gene
      (CSTB) that encodes an inhibitor of several lysosomal cathepsins. An unstable
      expansion of a dodecamer repeat in the CSTB promoter accounts for the majority of
      EPM1 disease alleles worldwide. We here describe a novel PCR protocol for
      detection of the dodecamer repeat expansion. We describe two novel EPM1
      associated mutations, c.149G > A leading to the p.G50E missense change and an
      intronic 18-bp deletion (c.168+1_18del), which affects splicing of CSTB. The
      p.G50E mutation that affects the conserved QVVAG amino acid sequence critical for
      cathepsin binding fails to associate with lysosomes. This further supports the
      previously implicated physiological importance of the CSTB-lysosome association.
      Expression of CSTB mRNA and protein was markedly reduced in lymphoblastoid cells
      of the patients irrespective of the mutation type. Patients homozygous for the
      dodecamer expansion mutation showed 5-10% expression compared to controls. By
      combining database searches with RT-PCR we identified several alternatively
      spliced CSTB isoforms. One of these, CSTB2, was also present in mouse and was
      analyzed in more detail. In real-time PCR quantification, CSTB2 expression was
      less than 5% of total CSTB expression in all human adult and fetal tissues
      analyzed. In patients homozygous for the minisatellite mutation, the level of
      CSTB2 was reduced similarly to that of CSTB implicating regulation from the same
      promoter. The physiological significance of CSTB2 remains to be determined.

PMID- 17003840
TI  - Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with
      hypospadias.
AB  - Hypospadias, one of the most common congenital abnormalities of the male external
      genitalia with elusive etiology, are caused by a defect in the normal development
      of the urethra, foreskin and ventral aspect of the penis. Evidences indicate that
      BMP4 and BMP7, two of those major factors in a signaling cascade involved in
      controlling the embryonic urethral development, play central roles in the normal
      development of the urethra, and that HOXA4 and HOXB6 play important roles in the
      development of skin in various tissues at the time course of the urethral
      development. We directly sequenced all these exons and exon-intron boundaries of
      the four genes in 90 unrelated Chinese patients with hypospadias. Thirteen
      different heterozygous nucleotide variations were identified for the first time
      in the four genes in 14 of 90 cases. Of the 13 variations, eight are missense:
      c.619C>G (p.H207D), c.668G>A (p.R223H), c.751C>T (p.H251Y) in BMP4; c.907C>T
      (p.R303C) in BMP7; c.385G>T (p.G129C), c.869C>G (p.S290C) in HOXA4; c.124C>A
      (p.P42T), c.367T>C (p.C123R) in HOXB6. None of these variations were found in 380
      control chromosomes. Amino-acid sequence alignments showed most of these changed
      amino acids are conserved across various vertebrate species. In a word, these
      findings, together with the indicated roles of the four genes, imply that it
      should not be random events for so many nucleotide variations found in the
      present study. Further functional studies are required to make the associations
      clear between these variants and hypospadias.

PMID- 17003841
TI  - The single-nucleotide polymorphism 309 in the MDM2 gene contributes to the Li
      Fraumeni syndrome and related phenotypes.
AB  - Li-Fraumeni syndrome (LFS) is an autosomal-dominant cancer predisposition
      syndrome of which the majority is caused by TP53 germline mutations and is
      characterised by different tumour types occurring at relatively young age.
      Recently, it was shown that a single-nucleotide polymorphism (SNP) in the MDM2
      gene, SNP309 (T>G variation), was associated with accelerated tumour formation in
      LFS patients who carry a TP53 germline mutation. To confirm this finding in
      different populations, we screened 25 Dutch and 11 Finnish TP53 mutation carriers
      for the presence of the SNP309 G allele in the MDM2 gene. Additionally, we
      investigated whether the SNP309 G allele plays a role in 72 Dutch TP53-negative
      LFS and LFS-related patients. In the TP53 germline mutation carriers, a
      significant difference was seen in the mean age of tumour onset for the SNP309 G
      allele group, that is, 29.7 years as compared to the SNP309 homozygous T group
      45.5 years (P=0.005). In patients of LFS and LFS-related TP53-negative families,
      no difference was seen in the mean age of tumour onset. However, this TP53
      negative group did show a significantly higher percentage of SNP309 homozygotes
      (G/G) compared to the general population (P=0.02). In conclusion, TP53 germline
      mutation carriers who have an SNP309 G allele have an earlier onset of tumour
      formation. The higher prevalence of MDM2 SNP309 homozygous G/G carriers in the
      TP53-negative group suggests that this allele contributes to cancer
      susceptibility in LFS and LFS-related families.

PMID- 17003842
TI  - Vasoactive intestinal peptide gene alterations in patients with idiopathic
      pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension is a progressive disease, characterised by
      increased proliferation of pulmonary artery smooth muscle cells, vasoconstriction
      and remodelling of the vascular wall leading to right heart failure and death.
      The idiopathic form is rare (idiopathic arterial primary hypertension (IPAH);
      formerly PPH, MIM# 178600). Our group correlated a deficiency in vasoactive
      intestinal peptide (VIP; MIM# 192320) levels in serum and lung tissue with the
      pathogenesis of IPAH. The aim of this study was to investigate the relevance of
      genetic alterations in VIP to the development of IPAH. We screened 10 patients
      (age 4-66 years) for alterations in the coding, the noncoding regions and the
      enhancer region of the VIP gene by direct sequencing. In eight of 10 patients, we
      found alterations compared to the wild-type sequence. We detected nine
      alterations. In the noncoding regions, eight alterations were in the introns 1,
      2, 3 and 4 (g.448G>A g.501C>T g.764T>C g.2267A>T g.2390C>T g.3144T>C g.3912A>G
      g.4857A>G). In the coding regions, a single alteration in the 3' untranslated
      region in exon 7 (g.8129T>C) was observed in five patients. It appeared in 46% of
      the control group. The frequency of this alteration in the coding region of the
      VIP gene could therefore not be correlated with the appearance of IPAH. Apart
      from the importance of VIP signalling, genetic and/or environmental modifiers
      might therefore contribute to the development and perpetuation of the disease.

PMID- 17003843
TI  - Malignant phyllodes tumor with heterologous liposarcomatous differentiation and
      tubular adenoma-like epithelial component.
AB  - Phyllodes tumor of the breast is a biphasic fibroepithelial neoplasm. A 30-year
      old woman presented with a 1-year history of a palpable, asymptomatic right
      breast mass without axillary lymphadenopathy and family history of breast
      carcinoma. Malignant phyllodes tumor was diagnosed. The authors present not
      previously described histological appearance of this tumor where an epithelial
      component was identical to that of a tubular adenoma of the breast, with the
      review of the literature. This is in addition to very rare liposarcomatous
      stromal differentiation in the malignant phyllodes tumor.

PMID- 17003844
TI  - Eradication rate of Helicobacter pylori according to genotypes of CYP2C19, IL-1B,
      and TNF-A.
AB  - BACKGROUND: Lansoprazole, amoxicillin, and clarithromycin are commonly used drugs
      for eradication of Helicobacter pylori (H. pylori). A few studies reported that
      the eradication rate was influenced by the functional polymorphism of CYP2C19,
      whose product metabolizes proton pomp inhibitors including lansoprazole. METHODS:
      This study examined the eradication rate among 67 participants in the
      polymorphism study who visited Daiko Medical Center, Nagoya University from July
      2004 to October 2005. The participants aged 20 to 69 years were classified into
      three group according to CYP2C19 genotype; rapid metabolizers (RM) with *1*1
      genotype, intermediate metabolizers (IM) with *1*2 or *1*3 genotype, and poor
      metabolizers (PM) with *2*2, *2*3, or *3*3 genotype. For the genotype
      classification, G681A (681G for *1 and 681A for *2) and G636A (636G for *1 and
      636A for *3) were genotyped by PCR with confronting two-pair primers (PCR-CTPP).
      They were also genotyped for IL-1B T-31C and TNF-A T-1031C by a duplex PCR-CTPP.
      RESULTS: The eradication rate was 70.0% for RM, 93.9% for IM, and 85.7% for PM.
      The difference in the rate between RM and IM+PM was statistically significant
      (p=0.025). The eradication rate was highest for those with IL-1B -31CC; the p
      value was marginal among the whole subjects (chi2=3.78, p=0.05) and not
      significant among the RM group (chi2=1.60, p=0.21). The genotypes of TNF-A T
      1031C had no associations with the eradication rate. But among the RM group, the
      odd ratio (OR) of the TNF-A CT for the eradication rate relative to TT was
      marginally reduced (OR=0.05, 95% confidence interval, 0.002-1.19). CONCLUSIONS:
      The present study confirmed the low eradication rate for RM. The reproduced
      finding provides evidence that the CYP2C19 genotype is useful to predict the
      success of the treatment. For the RM group, alternative regimens expected to be
      with a higher eradication rate will be recommended, especially to those with the
      TNF-A -1031C allele.

PMID- 17003845
TI  - A possible link between exercise-training adaptation and dehydroepiandrosterone
      sulfate- an oldest-old female study.
AB  - The purpose of this study was to determine the association between the level of
      salivary dehydroepiandrosterone sulfate (DHEA-S) and the magnitude of adaptation
      to exercise training in insulin sensitivity for aged females. A group of 16
      females, aged 80-93 years old, was divided into 2 groups according to their
      baseline DHEA-S levels: Lower Halves (N = 8) and Upper Halves (N = 8), and
      participated in a 4-month exercise intervention trial. Insulin response with an
      oral glucose tolerance test (OGTT), cholesterol, blood pressure (BP), motor
      performance, and DHEA-S were determined at baseline and 4 months after the
      training program. Glucose tolerance and body mass index (BMI) remained unchanged
      with training for both groups. Insulin, fasted cholesterol, diastolic blood
      pressure, reaction time, and locomotive function were significantly lowered by
      training only in the Upper Halves group. Changes in the area under curve of
      insulin (IAUC) were negatively correlated with the baseline DHEA-S level (R= -
      0.60, P < 0.05). The current study provides the first evidence that oldest-old
      subjects with low DHEA-S level appear to be poor responders to exercise-training
      adaptations.

PMID- 17003846
TI  - Analgesic, antiinflammatory, and ulcerogenic studies of meloxicam solid
      dispersion prepared with polyethylene glycol 6000.
AB  - Meloxicam is a nonsteroidal antiinflammatory drug, used in the treatment of
      rheumatoid arthritis and oestoarthritis. It is practically insoluble in water,
      leading to poor dissolution, variations in bioavailability, and gastric
      irritation on oral administration. In the attempt to reduce its gastric side
      effect and to increase aqueous solubility, physical mixture and solid dispersion
      of the drug were prepared with polyethylene glycol 6000. The analgesic,
      antiinflammatory, and ulcerogenic effects were assessed for physical mixture and
      solid dispersion in comparison with meloxicam alone. The results indicate that
      both physical mixture and solid dispersion possess better analgesic and
      antiinflammatory properties with less ulcerogenic potential when compared with
      pure meloxicam.

PMID- 17003847
TI  - RAT CYP3A and CYP2B1/2 were not associated with nevirapine-induced
      hepatotoxicity.
AB  - Nevirapine is an antiretroviral drug that is used for treatment as well as for
      the prevention of mother-to-child transmission of the human immunodeficiency
      virus (HIV). Unfortunately, its adverse effects, mainly hypersensitivity skin
      reactions and hepatotoxicity, have hampered the use of nevirapine. Since
      nevirapine-induced hepatotoxicity commonly occurs between 2-12 weeks of
      treatment, and nevirapine is a known inducer of human CYP3A and CYP2B6 isozymes,
      it was envisaged that the hepatotoxicity was due to activation of nevirapine to
      toxic metabolites by the induced enzymes. Therefore, the aim of this study was to
      use a rat model and determine the role of the rat analogues, rat CYP3A and
      CYP2B1/2, in nevirapine-induced hepatotoxicity. This was tested by the extent at
      which hepatotoxicity could be prevented when ketoconazole or thiotepa, known
      inhibitors of CYP3A and CYP2B1/2, respectively, were given one hour prior to
      administration of a hepatotoxic dose of nevirapine. It was shown here that
      nevirapine-induced hepatotoxicity only occurred in animals that were pretreated
      with an enzyme inducer (dexamethasone or nevirapine); that ketoconazole and
      thiotepa did not prevent the occurrence of nevirapine-induced hepatotoxicity; and
      that histopathologic examinations were more accurate than the use of liver
      enzymes in detecting the liver damage. This suggested that nevirapine-induced
      hepatotoxicity is closely associated with enzyme induction, and that liver
      function tests alone might not be good markers for determining nevirapine-induced
      hepatotoxicity. In conclusion, rat CYP3A and CYP2B1/2 may not be involved in the
      pathogenesis of nevirapine-induced hepatotoxicity, suggesting that a different
      enzyme inducible by nevirapine or dexamethasone may be responsible. However, this
      is yet to be proven in humans.

PMID- 17003848
TI  - Formulation and development of gastroretentive drug delivery system for
      ofloxacin.
AB  - The aim of the present study was to develop a delivery system wherein the
      retention of ofloxacin could be achieved for increased local action in gastric
      region against Helicobacter pylori infection. The formulation was optimized on
      the basis of in vitro buoyancy and in vitro release in citrate phosphate buffer
      (pH 3). The hydrodynamically balanced capsules were prepared by physical mixing
      of various grades of HPMC and poly(ethylene oxide) (PEO) alone as well as in
      combinations. Cellulose acetate pthalate, liquid paraffin, and ethyl cellulose
      were used as release modifiers so as to maintain release of drug over a period of
      12 h. The capsules prepared with PEOWSR 60K and drug coated with 2.5% ethyl
      cellulose gave the best in vitro percentage release and were taken as the
      optimized formulations. Various grades of Eudragit and PEO were used in
      combination for formulating floating microspheres using solvent diffusion
      technique for preparation of multiple unit system. The use of two different
      solvents (dichloromethane and ethanol) that differed in the rate of diffusion led
      to formation of a hollow core in the microspheres, which was partially
      responsible for the flotation ability. The in vitro release of the floating
      capsules and microspheres was found to be 96.02% and 95.83% in 12 h,
      respectively. Both the dosage forms follow Higuchi model for release from
      formulations. By fitting the in vitro release data of single unit dosage form
      into zero-order, first-order, and Higuchi model, it could be concluded that the
      release followed Higuchi model, as the correlation coefficient (R2 value) was
      higher than those in the other two release models. In both cases of single and
      multiple unit dosage form, R2 values for Higuchi model were found to be good,
      showing that drug release followed non-Fickian diffusion mechanism.

PMID- 17003849
TI  - Antiinflammatory and analgesic effects of Psidium guajava Linn. (Myrtaceae) leaf
      aqueous extract in rats and mice.
AB  - In many parts of Africa, the leaf, stem-bark, and roots of Psidium guajava Linn.
      (Family: Myrtaceae) are used traditionally for the management, control, and/or
      treatment of an array of human disorders. In an effort to scientifically appraise
      some of the ethnomedical properties of P. guajava leaf, and probe its efficacy
      and safety, the present study was undertaken to examine the antiinflammatory and
      analgesic properties of the plant's leaf aqueous extract in some experimental
      animal paradigms. The antiinflammatory property of the aqueous leaf extract was
      investigated in rats, using fresh egg albumin-induced pedal (paw) edema, while
      the analgesic effect of the plant extract was evaluated by the "hot-plate" and
      "acetic acid" test models of pain in mice. Diclofenac (100 mg/kg, i.p.) and
      morphine (10 mg/kg, i.p.) were used respectively as standard, reference
      antiinflammatory and analgesic agents for comparison. P. guajava leaf aqueous
      extract (PGE, 50-800 mg/kg, i.p.) produced dose-dependent and significant (p <
      0.05-0.001) inhibition of fresh egg albumin-induced acute inflammation (edema) in
      rats. The plant extract (PGE, 50-800 mg/kg, i.p.) also produced dose-dependent
      and significant (p < 0.05-0.001) analgesic effects against thermally and
      chemically induced nociceptive pain in mice. The numerous tannins, polyphenolic
      compounds, flavonoids, ellagic acid, triterpenoids, guiajaverin, quercetin, and
      other chemical compounds present in the plant are speculated to account for the
      observed antiinflammatory and analgesic effects of the plant's leaf extract. In
      summary, the findings of this experimental animal study indicate that the leaf
      aqueous extract of P. guajava possesses analgesic and antiinflammatory
      properties, and thus lend pharmacological credence to the suggested ethnomedical,
      folkloric uses of the plant in the management and/or control of painful,
      arthritic and other inflammatory conditions in some rural communities of Africa.

PMID- 17003851
TI  - Gateways to clinical trials.
AB  - Gateways to Clinical Trials are a guide to the most recent clinical trials in
      current literature and congresses. The data in the following tables have been
      retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the
      drug discovery and development portal, http://integrity.prous.com This issue
      focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine
      triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra,
      angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine
      hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin
      aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine;
      Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab,
      certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride,
      clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran
      etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine,
      dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa
      (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab,
      emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram
      oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe;
      Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic
      acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate,
      indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir
      sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide,
      levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine,
      lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid,
      neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid
      hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b,
      pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000,
      Pseudostat; R24, rasburicase, RHAMM R3 peptide, rilonacept, rosuvastatin calcium,
      rotavirus vaccine, rufinamide; Sabarubicin hydrochloride, SHL-749, sirolimus
      eluting stent, SLx-2101, sodium butyrate, sorafenib, SU-6668; TachoSil,
      tadalafil, taxus, tegaserod maleate, telbivudine, tenofovir disoproxil fumarate,
      teriparatide, tetramethylpyrazine, teverelix, tiotropium bromide, tipifarnib,
      tirapazamine, tolvaptan, TransvaxTM hepatitis C vaccine, treprostinil sodium;
      Valganciclovir hydrochloride, valsartan/amlodipine, vandetanib, vardenafil
      hydrochloride hydrate, vatalanib succinate, veglin, voriconazole; Yttrium 90
      (90Y) ibritumomab tiuxetan; Zileuton, zotarolimus, zotarolimus-eluting stent.

PMID- 17003850
TI  - The effect of CYP2C19 substrate on the metabolism of melatonin in the elderly: A
      randomized, double-blind, placebo-controlled study.
AB  - The metabolism of melatonin to 6-sulphatoxymelatonin (aMT6S) and N
      acetylserotonin (NAS) is catalyzed by cytochrome-P450 (CYP) isozymes CYP1A2 and
      CYP2C19 respectively. We studied the in vivo effect of CYP2C19 substrate
      (citalopram, omepratzole, or lansopratzole) on the metabolism of endogenous and
      exogenous melatonin by measuring the excretion of urinary aMT6S, the main
      metabolite of melatonin, and a reliable estimate of plasma melatonin in 15
      insomniac psychogeriatric inpatients. The effect of melatonin treatment on sleep
      parameters was also assessed. The patients with or without CYP2C19 substrate were
      treated for 21 days randomly in a double-blind manner with placebo or 2 mg
      exogenous melatonin orally. aMT6S excretions were measured radioimmunologically
      from night urine at baseline (day 0), on day 21, and one day after the treatment
      was discontinued (day 22). Sleep parameters were assessed using the Sleep
      Assessment Scale and the Sleep Quality Scale. In the control patients receiving
      only melatonin, aMT6S excretion increased 72-fold and returned to baseline on day
      22. In the patients receiving melatonin + CYP2C19 substrate, aMT6S excretion
      increased 156-fold and was, on day 22, still 6.4-fold higher than at baseline (p
      = 0.04). The 22/0 day aMT6S excretion ratio was 10-fold higher in the patients
      treated with melatonin + CYP2C19 substrate when compared with that in the
      subjects treated with placebo + CYP2C19 substrate (p = 0.02). CYP2C19 substrate
      did not affect the metabolism of endogenous melatonin. The sleep parameters in
      the patients on melatonin treatment did not differ from those in the patients
      treated with placebo. In conclusion, it may be inferred that CYP2C19 substrate
      slows the metabolism of exogenous melatonin and increases its bioavailability, as
      shown by the augmented excretion of aMT6S, probably by inhibiting the conversion
      of melatonin to NAS via CYP2C19 isozyme. Melatonin therapy may not affect the
      sleep parameters in our psychogeriatric inpatients.

PMID- 17003852
TI  - A pragmatic and readily implemented quality control strategy for HPLC-MS and GC
      MS-based metabonomic analysis.
AB  - Metabonomic/metabolomic studies can involve the analysis of large numbers of
      samples for the detection of biomarkers and confidence in the analytical data,
      generated by methods such as GC and HPLC-MS, requires active measures on the part
      of the analyst. However, quality control for complex multi-component samples such
      as biofluids, where many of the components of interest in the sample are unknown
      prior to analysis, poses significant problems. Here the repeat analysis of a
      pooled sample throughout the run, thereby enabling the analysis to be monitored
      and controlled using targeted inspection of the data and pattern recognition, is
      advocated as a pragmatic solution to this problem.

PMID- 17003853
TI  - The role of biosensors in the detection of emerging infectious diseases.
AB  - Global biosecurity threats such as the spread of emerging infectious diseases
      (i.e., avian influenza, SARS, Hendra, Nipah, etc.) and bioterrorism have
      generated significant interest in recent years. There is considerable effort
      directed towards understanding and negating the proliferation of infectious
      diseases. Biosensors are an attractive tool which have the potential to detect
      the outbreak of a virus and/or disease. Although there is a host of technologies
      available, either commercially or in the scientific literature, the development
      of biosensors for the detection of emerging infectious diseases (EIDs) is still
      in its infancy. There is no doubt that the glucose biosensor, the gene chip, the
      protein chip, etc. have all played and are still playing a significant role in
      monitoring various biomolecules. Can biosensors play an important role for the
      detection of emerging infectious diseases? What does the future hold and which
      biosensor technology platform is suitable for the real-time detection of
      infectious diseases? These and many other questions will be addressed in this
      review. The purpose of this review is to present an overview of biosensors
      particularly in relation to EIDs. It provides a synopsis of the various types of
      biosensor technologies that have been used to detect EIDs, and describes some of
      the technologies behind them in terms of transduction and bioreceptor principles.

PMID- 17003854
TI  - Multi-analyte immunoassay using cleavable tags and microchip micellular
      electrokinetic chromatography.
AB  - A new multi-analyte immunoassay designed to screen for several biomarkers using
      cleavable tag chemistry and micellular electrokinetic chromatography was
      evaluated.

PMID- 17003855
TI  - Boronate functionalised polymer monoliths for microscale affinity chromatography.
AB  - Novel macroporous monolithic stationary phase materials suitable for microscale
      boronate affinity chromatography were developed.

PMID- 17003857
TI  - Efficient "total" extraction of perfluorooctanoate from polytetrafluoroethylene
      fluoropolymer.
AB  - To determine the optimum conditions for the complete extraction of
      perfluorooctanoate (PFO) from polytetrafluoroethylene fluoropolymers, sample
      preparation and pressurized solvent extraction (PSE) conditions were
      investigated. Solvent extraction temperature, solvent residence time, relaxation
      time between extractions, and the effects of heating before PSE showed that
      methanol at 150 degrees C extraction temperature and a 12 min solvent residence
      time were the most efficient conditions. Preheating the polymer before extraction
      at 150 degrees C for 24 h significantly enhanced the quantity of PFO removed.
      Heating above 150 degrees C resulted in loss of PFO. PFO was determined by liquid
      chromatography with tandem mass spectrometry.

PMID- 17003856
TI  - Photocleavable peptide hydrogel arrays for MALDI-TOF analysis of kinase activity.
AB  - We have developed an acrylamide copolymerization strategy to immobilize
      acrylamide labeled peptides and proteins into a hydrogel surface and detect their
      modifications using MALDI-TOF mass spectrometry. Copolymerization into hydrogels
      is robust, compatible with "off-the-shelf" chemistry, and yields materials and
      surfaces that are stable to aqueous or organic solvents, drying, high or low
      temperature, high or low pH, oxidizing agents, sonication, mechanical contact,
      etc. The use of acrylamide hydrogels allows immobilization of substrates in a
      hydrated environment that can be used both as a biological reaction matrix and as
      a MALDI target. In our strategy, a substrate peptide was designed in a modular
      fashion to include both modification site and affinity domains. It was labeled
      with an acrylamide functionality using a generalized chemistry and covalently
      attached to the surface with a photocleavable linker, allowing for aggressive
      washing to remove any fouling, followed by selective release for MALDI-TOF
      analysis. Using this system we were able to analyze and compare v-Abl (truncated)
      and c-Abl (full-length) kinase activity on a peptide substrate with an affinity
      domain specific for the full-length kinase, observing excellent overall
      reproducibility in the extent of phosphorylation detected. This work serves as
      proof of principle for modular substrate design strategies for mass spectrometry
      readable biosensors.

PMID- 17003859
TI  - Comparative evaluation of bioactivity change of crystalline trypsin during
      compression by chemoinformatics and 2-D Fourier-transform infrared spectroscopy.
AB  - The purpose of this study is to develop a method of evaluating the enzymatic
      activity of trypsin in a solid-state based on Fourier transform infrared (FT-IR)
      spectra using chemoinformatics and two-dimensional (2-D) correlation
      spectroscopy. Crystalline trypsin powders are compressed at 0-4000 kg cm-2 by a
      compression/tension tester. The enzymatic activity of trypsin is assayed by the
      kinetic degradation method. Spectra of 10 calibration sample sets are recorded 3
      times with a FT-IR spectrometer. The maximum intensity of FT-IR spectra and
      enzymatic activity of trypsin decrease as the compression pressure increases. The
      FT-IR spectra of trypsin samples are subjected to a principal component
      regression (PCR). A plot of the calibration data obtained is made between the
      actual and predicted trypsin activity based on a two-component model with
      gamma2=0.909 (n=30). The regression vector is almost the same as the loading
      vector for PC1. On the other hand, a generalized two-dimensional (2-D)
      correlation spectroscopic method is applied to FT-IR spectra of compressed
      trypsin. The result is consistent with that of the chemoinformatics method. The
      FT-IR chemoinformatics method allows for solid-state quantitative analysis of the
      bioactivity of the bulk powder of a polypeptide drug.

PMID- 17003858
TI  - Microflow injection system based on a multicommutation technique for nitrite
      determination in wastewaters.
AB  - In this work a microflow structure, suitable for micro-FIA (micro flow injection
      analysis), will be described, evaluated and applied to real samples.
      Microchannels, the detector flow cell and input/output ports have been
      micromachined in silicon and sealed with anodically bonded Pyrex glass. The
      channels are defined by etching approximately 200 microm depth in silicon using a
      dry reactive ion etching (RIE) process. Optical windows integrated in the chip
      structure allow simple absorbance/transmission measurements to be made. The
      optical measurements were made using an LED as emitter (lambda=525 nm) and a
      photodiode as a detector. A Visual-Basic program has been developed to control an
      automatic burette, three-way solenoid valves and the data acquisition system. The
      micro-FIA for nitrite determination using the Griess-Ilosvay reaction has been
      implemented for the on-line monitoring of wastewater treatment plants (WWTPs).
      The multicommutation concept has been applied in order to enhance the mixing
      process inside the microsystem. Tandem streams of reagent and sample were
      generated and evaluated at different commutation frequencies. Two optimal
      frequencies, 400/200 ms and 150/450 ms, were found to be the most suitable ones.
      The first commutation ratio gave rise to wide linear working range (0-250 ppm),
      in spite of a high detection limit (0.35 ppm) and a low sensitivity (0.0041+/
      0.0004 AU ppm-1). With the second ratio, the working linear range was smaller (0
      50 ppm) but the detection limit (0.17 ppm) and the sensitivity (0.0091+/-0.0003
      AU ppm-1) improved remarkably. Finally, real samples with a high nitrite
      concentration (0-1500 ppm) coming from a study of kinetic inhibition in the
      nitrification process at a WWTP has been analysed with the proposed micro-FIA
      system. The obtained results have allowed the corroboration of the model of
      inhibition by the nitrite ion with great exactitude.

PMID- 17003860
TI  - PDMS-based microfluidics for proteomic analysis.
AB  - A microfluidic poly(dimethylsiloxane) (PDMS) microdevice was realized, combining
      on-line protein electrophoretic separation, selection, and digestion of a protein
      of interest for identification by mass spectrometry. The system includes eight
      integrated valves and one micropump dedicated to control the flow operations.
      Myoglobin was successfully isolated from bovine serum albumin (BSA), then
      selected using integrated valves and digested in a rotary micromixer. Proteolytic
      peptides were recovered from the micromixer for protein identification. Total
      analysis from sample injection to protein identification is performed under 30
      minutes, with samples of tens of nanolitres. The paper shows that PDMS technology
      can be successfully used for integrating complex preparation protocols of proteic
      samples prior to MS analysis.

PMID- 17003861
TI  - Tailored xerogel-based sensor arrays and artificial neural networks yield
      improved O2 detection accuracy and precision.
AB  - The objective of this research is to develop arrays of tuned chemical sensors
      wherein each sensor element responds to a particular target analyte in a unique
      manner. By creating sol-gel-derived xerogels that are co-doped with two
      luminophores at a range of molar ratios, we can form suites of sensor elements
      that can exhibit a continuum of response profiles. We trained an artificial
      neural network (ANN) to "learn" to identify the optical outputs from these
      xerogel-based sensor arrays. By using the ANN in concert with our tailored sensor
      arrays we obtained a 5-10 fold improvement in accuracy and precision for
      quantifying O2 in unknown samples. We also explored the response characteristics
      of these types of sensor elements after they had been contacted with rat
      plasma/blood. Contact with plasma/blood caused approximately 15% of the
      luminophore molecules within the xerogels to become non-responsive to O2. This
      behavior is consistent with rat albumin blocking certain pore sub-populations
      within the mesoporous xerogel matrix thereby limiting O2 access to the
      luminophores.

PMID- 17003862
TI  - Raman spectroscopy as a process analytical technology tool for the understanding
      and the quantitative in-line monitoring of the homogenization process of a
      pharmaceutical suspension.
AB  - The aim of this study was to propose a Process Analytical Technology (PAT)
      strategy for the quantitative in-line monitoring of an aqueous pharmaceutical
      suspension using Raman spectroscopy. A screening design was used to study the
      significance of process variables (mixing speed and height of the stirrer in the
      reactor) and of formulation variables (concentration of the active pharmaceutical
      ingredient (API) ibuprofen and the viscosity enhancer (xanthan gum)) on the time
      required to homogenize an aqueous pharmaceutical model suspension as response
      variable. Ibuprofen concentration (10% and 15% (w/v)) and the height of stirrer
      (position 1 and 2) were discrete variables, whereas the viscosity enhancer
      (concentration range: 1-2 g L-1) and the mixing speed (700-1000 rpm) were
      continuous variables. Next, a multilevel full factorial design was applied to
      study the effect of the remaining significant variables upon the homogenization
      process and to establish the optimum conditions for the process. Interactions
      between these variables were investigated as well. During each design experiment,
      the conformity index (CI) method was used to monitor homogeneity of the
      suspension mixing system in real-time using Raman spectroscopy in combination
      with a fibre optical immersion probe. Finally, a principal component regression
      (PCR) model was developed and evaluated to perform quantitative real-time and in
      line measurements of the API during the mixing process. The experimental design
      results showed that the suspension homogenization process is an irregular
      process, for which it is impossible to model the studied variables upon the
      measured response variable. However, applying the PCR model it is possible to
      predict in-line and real-time the concentration of the API in a suspension during
      a mixing process. In this study, it is shown that Raman spectroscopy is a
      suitable PAT tool for the control of the homogenization process of an aqueous
      suspension. Raman spectroscopy not only allowed real-time monitoring of the
      homogeneity of the suspension, but also helped (in combination with experimental
      design) to understand the process. Further, the technique allowed real-time and
      in-line quantification of the API during the mixing process.

PMID- 17003863
TI  - Improved curve fitting procedures to determine equilibrium binding constants.
AB  - For ligand-biomacromolecule titration experiments it has been traditional
      practice to extract parameters such as the equilibrium binding constant K and the
      number of bases per ligand binding site n with relatively labour intensive
      methods, usually based on single wavelength data, such as the difference method
      by Rodger and Norden coupled together with a Scatchard plot. Presented in this
      paper are both the theory and a least squares fitting method to derive parameters
      such as K and n more directly from all spectral non-linear experimental data.
      Both the case of non competitive binding of a metal complex ligand to DNA and the
      case of displacement by a metal complex ligand of an ethidium marker attached to
      the DNA are considered. This work may be applied directly to reduce experimental
      data produced by a spectropolarimeter (for circular or linear dichroism) or a
      spectrophotometer (for fluorescence or UV-Vis spectroscopy).

PMID- 17003864
TI  - Hyperspectral NIR imaging for calibration and prediction: a comparison between
      image and spectrometer data for studying organic and biological samples.
AB  - A hyperspectral image in the near infrared contains thousands of position
      referenced spectra. After imaging reference materials of known composition it is
      possible to build Partial Least Squares (PLS) regression models for predicting
      unknown compositions from new images or spectra. In this paper a comparison is
      made between spectra from a hyperspectral image and spectra from two
      spectrometers: a scanning grating instrument with rotating sample holders and an
      FT-NIR instrument utilizing a fiber-optic probe. The raw spectra and the quality
      of the PLS calibration models and predictions are compared. Two sample datasets
      consist of a set of 13 designed artificial mixtures of pure constituents and a
      selection of 13 sampled cheeses. The prediction error from the hyperspectral
      image spectra is between that of the two spectrometers. For a typical food
      sample, the average bias [and replicate standard deviation] was -0.6% [0.5%] for
      protein and -0.2% [1.3%] for fat. Comparable values for the best spectrometer
      were -0.2% bias for protein and -0.5% for fat. Some of the advantages of working
      with hyperspectral images are highlighted: the simultaneous exploration of
      representations of both spectral and spatial data, and the analysis of
      concentration profiles and concentration maps all contribute to better
      characterization of organic and biological materials.

PMID- 17003865
TI  - DNA-duplexes containing abasic sites: correlation between thermostability and
      acoustic wave properties.
AB  - Aldehydic apurinic or apyrimidinic sites that lack a nucleobase moiety are one of
      the most common forms of toxic lesions in DNA. In the present study, a close
      structural analog of such a site, the 2-(hydroxymethyl) tetrahydrofuranyl
      residue, was synthesized in order to act as a model for damaged nucleic acid
      probes. Prepared oligodeoxyribonucleotides containing one, two or three abasic
      sites were hybridized to complementary sequences immobilized on a gold surface
      using the neutravidin-biotin interaction for study by thickness shear mode
      acoustic wave detector. Measurement of the complex electrical impedance of an AT
      cut quartz device with immobilized biotinylated nucleotide allowed the detection
      of changes of series resonance frequency, Deltafs, and motional resistance, Rm,
      associated with duplex formation. The changes as detected by the acoustic wave
      method correlated well with the thermostability of DNA duplexes in solution. With
      respect to the latter, UV-monitored melting curves indicate that both the number
      of sites and their localization in the double-stranded structure influence the
      amount by which a 19 b.p. duplex is destabilized. The presence of 3 abasic sites
      completely destabilized the DNA duplex.

PMID- 17003866
TI  - A hydrophilic interaction chromatography coupled to a mass spectrometry for the
      determination of glutathione in plant somatic embryos.
AB  - An electrospray ionization mass spectrometric (ESI-MS) determination of
      glutathione (GSH), a sulfur-containing tripeptide (gamma-Glu-Cys-Gly) with
      regulation and detoxication functions in metabolisms of most living organisms,
      from nanomolar to micromolar levels is described. A hydrophilic interaction
      chromatography (HILIC) with an isocratic elution using a mobile phase containing
      acetonitrile and an aqueous 0.00005% solution of trifluoroacetic acid (60/40%,
      v/v) was applied for the separation of GSH. The peptide detection was achieved in
      the presence of L-ascorbic acid which significantly enhanced the signal intensity
      of the molecular ion GSH [M+H]+ (m/z 308). The calibration curve was linear
      (R2=0.9995) in the concentration range from 2 nM to 10 microM with a detection
      limit (LOD, S/N=3) of 0.5 nM. The excellent detection limit, and the excellent
      selectivity and high reproducibility of this method enabled determination of GSH
      in a single plant somatic embryo of a Norway spruce (Picea abies). The average
      amount of GSH in the single somatic embryos (n=18) was 9 pmol per embryo. Owing
      to our results, it can be supposed that the proposed HILIC/ESI-MS analysis might
      be used for GSH determination in microscopic cell structures and in single cell
      analyses.

PMID- 17003867
TI  - Characteristics of the series resonant-frequency shift of a quartz crystal
      microbalance in electrolyte solutions.
AB  - We report the novel characteristics of the series resonant-frequency shift,
      DeltaF, of a one-face sealed quartz crystal microbalance (QCM) in solutions of
      monovalent electrolytes and divalent electrolytes. In the present study, we used
      NaCl, KCl, LiCl, NaNO3 and CH3COONa as monovalent electrolytes, and MgCl2, CaCl2,
      MgSO4 and Na2SO4 as divalent electrolytes. These experiments reveal that, in all
      the solutions, the DeltaF values vary linearly with an increase in the square
      root of the density-viscosity product of the solutions, and the immersion angle
      dependence of DeltaF appears. Moreover, we have found that the intercept values
      of DeltaF are dependent only on the cation species, and that the slope values of
      DeltaF with the viscosity and density of the solutions are related only to the
      valence of ions. We also suggest that the DeltaF values are independent of anion
      species, conductivity and permittivity of the solutions.

PMID- 17003868
TI  - F-block N-heterocyclic carbene complexes.
AB  - N-Heterocyclic carbenes (NHCs) can bind as two-electron sigma-donor ligands to
      lanthanide and actinide metal cations. In this review we summarise how the
      incorporation of an anionic group (alkoxide or amido), to form heterobidentate
      NHC ligands, allows the synthesis of a range of f-block NHC adducts. The
      tethering group also allows the lability of the NHC group, and its subsequent
      reactivity, to be studied. We include a brief survey of the known, structurally
      characterised f-element-NHC bond distances, and a range of substrates that react
      to displace the metal-bound NHC group.

PMID- 17003869
TI  - Self-assembled nanostructures with tridentate cyclometalated platinum(II)
      complexes.
AB  - Self-assembly of positively charged and charge-neutral tridentate cyclometalated
      platinum(II) complexes leads to nanowires and the drop-cast film containing these
      nanowires behaves as a n-type semiconductor.

PMID- 17003870
TI  - A diverse suite of spiroacetals, including a novel branched representative, is
      released by female Bactrocera tryoni (Queensland fruit fly).
AB  - A remarkably diverse suite of spiroacetals including a novel member of the rare,
      branched chain class has been identified in the glandular secretions of
      Bactrocera tryoni, the most destructive horticultural pest in Australia.

PMID- 17003871
TI  - Synthetic, structural and theoretical studies of amidinate and guanidinate
      stabilised germanium(I) dimers.
AB  - The neutral germanium(i) dimers, [{Ge(Piso)}(2)] and [{Ge(Giso)}(2)], Piso =
      [(ArN)(2)CBu(t)](-), Giso = [(ArN)(2)CNPr(i)(2)](-), Ar = C(6)H(3)Pr(i)(2)-2,6,
      which are stabilised by bulky amidinate and guanidinate ligands respectively,
      have been prepared by reduction of the corresponding germanium(ii) chlorides,
      [Ge(Piso)Cl] and [Ge(Giso)Cl]; theoretical studies suggest that the Ge-Ge bonds
      of [{Ge(Piso)}(2)] and [{Ge(Giso)}(2)] are associated with their HOMOs, whilst
      their LUMOs have substantial Ge-Ge pi-bonding character.

PMID- 17003872
TI  - Elucidation of the Streptomyces coelicolor pathway to 4-methoxy-2,2'-bipyrrole-5
      carboxaldehyde, an intermediate in prodiginine biosynthesis.
AB  - The biosynthetic pathway to 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC), a
      key intermediate in the biosynthesis of prodiginine antibiotics in Streptomyces
      coelicolor, has been elucidated using a combination of gene replacements and
      feeding experiments with chemically synthesised MBC and a synthetic analogue of a
      pathway intermediate.

PMID- 17003873
TI  - Dual colour, microarray-based, analysis of 10,000 protease substrates.
AB  - A 10,000 member PNA-encoded library of FRET based peptides was synthesised for
      global analysis of protease cleavage specificity; analysis was achieved using a
      DNA microarray and consumed minimal quantities of enzyme (60 pmole) and library
      (3.5 nmole).

PMID- 17003874
TI  - Scalable synthesis of activated carbon with superparamagnetic properties.
AB  - Magnetic activated carbons were obtained by in situ formation of coated
      superparamagnetic iron nanoparticles in the pores of carbons initially
      impregnated with ferric salt solution.

PMID- 17003875
TI  - Synthesis and structural characterization of tris(2-seleno-1-mesitylimidazolyl)
      hydroborato complexes: a new type of strongly electron donating tripodal selenium
      ligand.
AB  - A new tripodal ligand that features three selenium donors, namely the tris(2
      seleno-1-mesitylimidazolyl)hydroborato ligand, [Tse(Mes)], has been constructed
      via the reaction of KBH(4) with 1-mesitylimidazole-2-selone; comparison of the IR
      spectroscopic data of [Tse(Mes)]Re(CO)(3) with those of a variety of related
      LRe(CO)(3) complexes demonstrates that the [Tse(Mes)] ligand is more strongly
      electron donating than Cp, Cp*, [Tp], [Tp(Me(2))] and [Tm(Mes)] ligands.

PMID- 17003876
TI  - First mixed hydrazide/hydroxylamide metal aggregates.
AB  - The first organometallic clusters of mixed hydrazide/hydroxylamide clusters of
      zinc, [Zn(MeZn)(4)(HNNMe(2))(2)(ONEt(2))(4)] and
      {Zn(EtZn)(4)[HNN(CH(2))(5)](2)(ONEt(2))(4)} were synthesized in one-pot synthesis
      protocols from dialkylzinc solutions, substituted hydrazines and N,N
      diethylhydroxylamine; competing for the Zn atoms, the different binding
      properties of hydrazide and hydroxylamide ligands in these heteroleptic clusters
      are discussed.

PMID- 17003877
TI  - Silica-supported tantalum clusters: catalyst for alkane conversion.
AB  - Silica-supported tantalum clusters (on average, approximately tritantalum) were
      formed by the treatment, in either H(2) or ethane, of adsorbed Ta(CH(2)Ph)(5);
      the supported catalyst is active for ethane conversion to methane and propane at
      523 K, with the used catalyst containing clusters of the same average nuclearity
      as the precursor.

PMID- 17003878
TI  - Acetylenedithiolate: alkyne complex formation renders it a dithiolate chelate
      ligand.
AB  - The isostructural complexes [{Tp'W(CO)(2)(eta(2)-C(2)S(2))}(2)M] (M = Ni, Pd, Pt)
      show that the eta(2)-C,C'-alkyne complexes of acetylenedithiolate at
      [Tp'W(CO)(2)](+) can generally act as dithiolate chelate ligands, leading to
      dithiolene type complexes.

PMID- 17003879
TI  - Synergistic effect of ligating and ionic functions, prearranged on a
      calix[4]arene.
AB  - The covalent attachment of two CMPO-functions and two anionic Cosan groups to the
      narrow rim of tert-butylcalix[4]arene leads to a dramatic increase of the
      extraction efficiency for the cone isomer; Am(3+) is removed from 5 x 10(-8) M
      solution to more than 99% by a single extraction step with a 3 x 10(-6) M
      solution of the calixarene.

PMID- 17003880
TI  - High-efficiency (7.2%) flexible dye-sensitized solar cells with Ti-metal
      substrate for nanocrystalline-TiO2 photoanode.
AB  - High-efficiency flexible dye-sensitized solar cells were fabricated with a Ti
      metal foil substrate for photo anode and using a Pt-electrodeposited counter
      electrode on ITO/polyethylene naphthalate (ITO/PEN); these devices were
      characterized by incident photon-to-current efficiency (IPCE), optical
      transmittance and electrical impedance spectroscopy.

PMID- 17003881
TI  - 3-Amino-6-nitroamino-tetrazine (ANAT)-based energetic salts.
AB  - The synthesis and properties of several new high-nitrogen materials with 3-amino
      6-nitroamino-tetrazine (ANAT) as the anion are reported; all salts were fully
      characterized by IR and NMR spectroscopy, and elemental analysis.

PMID- 17003882
TI  - Synthesis of star-shaped poly(epsilon-caprolactone) via'click' chemistry and
      'supramolecular click' chemistry.
AB  - The synthesis of star-shaped poly(epsilon-caprolactone) is described via azide
      alkyne cycloaddition ('click' chemistry) and via self-assembly of polymeric
      ligands into [2 x 2] grid-like metal complexes ('supramolecular click'
      chemistry).

PMID- 17003883
TI  - Direct observation of adsorbed H2-framework interactions in the Prussian Blue
      analogue MnII3[CoIII(CN)6]2: the relative importance of accessible coordination
      sites and van der Waals interactions.
AB  - Selective recovery of the guest-framework interactions for H(2) adsorbed in a
      nanoporous Prussian Blue analogue, through differential X-ray and neutron pair
      distribution function analysis at ca. 77 K, suggests that the H(2) molecule is
      disordered about a single position at the centre of the pore,
      ((1/4),(1/4),(1/4)), without binding at accessible Mn(II) sites.

PMID- 17003884
TI  - NiII(TPA) as an efficient catalyst for alkane hydroxylation with m-CPBA.
AB  - A simple Ni(II)(TPA) complex [TPA = tris(2-pyridylmethyl)amine] has been
      demonstrated to act as an efficient turnover catalyst for alkane hydroxylation
      with m-CPBA (m-chloroperbenzoic acid), in which contribution of a NiO(+) (nickel
      oxo) type active oxygen species is suggested.

PMID- 17003885
TI  - The synthesis, X-ray structure and fluxional behaviour of an ytterbium(II)
      phenalenide complex.
AB  - The first lanthanoid complexes containing delocalized phenalenide anions are
      reported and the rapid migration of the eta(3)-bonded metal centre between the
      three rings of the pi-system is the first report of a degenerate haptotropic
      rearrangement in organolanthanoid chemistry.

PMID- 17003886
TI  - A novel electrochemical device for the disinfection of fluids by OH radicals.
AB  - This paper describes a novel, composite device, based not on optical excitation
      but on the transfer of holes from Si to the TiO(2)/air or TiO(2)/water interface,
      for the disinfection and detoxification of fluid streams.

PMID- 17003887
TI  - Ratiometric fluorescence detection of a tag fused protein using the dual-emission
      artificial molecular probe.
AB  - We have successfully developed a ratiometric detection system for protein of
      interest using the complementary recognition pair of the tetra-aspartate peptide
      tag and the SNARF-appended Zn(ii)-DpaTyr probe.

PMID- 17003888
TI  - Reversible physical absorption of SO2 by ionic liquids.
AB  - Ionic liquids can reversibly absorb large amounts of molecular SO(2) gas under
      ambient conditions with the gas captured in a restricted configuration, possibly
      allowing SO(2) to probe the internal cavity structures in ionic liquids besides
      being useful for SO(2) removal in pollution control.

PMID- 17003889
TI  - Terminal stibinidene ligands. Generation of CpCp*Hf=Sb(dmp) and trapping
      reactions with PMe3 and 2-butyne.
AB  - Treating CpCp*HfMe(OTf) (1) with LiSbH(dmp) results in formation of
      CpCp*HfMe(SbHdmp), which undergoes alpha-abstraction to liberate methane and
      generate CpCp*Hf=Sb(dmp), which is thermally unstable but can be trapped with
      PMe(3) or 2-butyne to give CpCp*Hf(PMe(3))=Sb(dmp) (2) and CpCp*Hf[eta(2)
      Sb,C:Sb(dmp)C(Me)=C(Me)] (3), respectively.

PMID- 17003890
TI  - Model systems for flavoenzyme activity: recognition and redox modulation of
      flavin mononucleotide in water using nanoparticles.
AB  - We have used mixed monolayer protected gold clusters (MMPCs) to provide
      flavoenzyme model systems with a high affinity and ability to modulate cofactor
      reduction potential.

PMID- 17003891
TI  - Syntheses, structures, and magnetic characterization of dicyanometalate(II)
      building blocks: [NEt4][(Tp*)MII(CN)2] [MII = Cr, Co, Ni; Tp* = hydridotris(3,5
      dimethylpyrazol-1-yl)borate].
AB  - The syntheses and structures of three dicyanometalate(II) complexes,
      [NEt(4)][(Tp*)M(II)(CN)(2)].nMeCN.(1/2)Et(2)O (M(II) = Cr, 1, n = (1/2); Co, 2, n
      = 1; Ni, 3, n = 1) are described; magnetic studies indicate that 3 is diamagnetic
      while 1 and 2 are paramagnetic high- and low-spin S = 2 and (1/2) complexes,
      respectively.

PMID- 17003892
TI  - Chemistry at high pressure.

PMID- 17003893
TI  - Origins of life and biochemistry under high-pressure conditions.
AB  - Life on Earth can be traced back to as far as 3.8 billion years (Ga) ago. The
      catastrophic meteoritic bombardment ended between 4.2 and 3.9 Ga ago. Therefore,
      if life emerged, and we know it did, it must have emerged from nothingness in
      less than 400 million years. The most recent scenarios of Earth accretion predict
      some very unstable physico-chemical conditions at the surface of Earth, which, in
      such a short time period, would impede the emergence of life from a proto-biotic
      soup. A possible alternative would be that life originated in the depth of the
      proto-ocean of the Hadean Earth, under high hydrostatic pressure. The large body
      of water would filter harmful radiation and buffer physico-chemical variations,
      and therefore would provide a more stable radiation-free environment for pre
      biotic chemistry. After a short introduction to Earth history, the current
      tutorial review presents biological and physico-chemical arguments in support of
      high-pressure origin for life on Earth.

PMID- 17003894
TI  - Nanomaterials under high-pressure.
AB  - The use of high-pressure for the study and elaboration of homogeneous
      nanostructures is critically reviewed. Size effects, the interaction between
      nanostructures and guest species or the interaction of the nanosystem with the
      pressure transmitting medium are emphasized. Phase diagrams and the possibilities
      opened by the combination of pressure and temperature for the elaboration of new
      nanomaterials is underlined through the examination of three different systems:
      nanocrystals, nano-cage materials which include fullerites and group-14
      clathrates, and single wall nanotubes. This tutorial review is addressed to
      scientist seeking an introduction or a panoramic view of the study of
      nanomaterials under high-pressure.

PMID- 17003895
TI  - High pressure effects in anaesthesia and narcosis.
AB  - There is growing interest in determining the effects of high pressure on
      biological functions. Studies of brain processes under hyperbaric conditions can
      give a unique insight into phenomena such as nitrogen narcosis, inert gas
      anaesthesia, and pressure reversal of the effects of anaesthetic and narcotic
      agents. Such research may shed light on the action of anaesthetics, which remains
      poorly understood, and on the nature of consciousness itself. Various studies
      have established the behavioural response of organisms to hyperbaric conditions,
      in the presence or absence of anaesthetic agents. At the molecular level, X-ray
      crystallography has been used to investigate the incorporation of species like Xe
      in hydrophobic pockets within model ion channels that may account for pressure
      effects on neuronal transmission. New magnetic resonance imaging techniques are
      providing tomographic three-dimensional images that detail brain structure and
      function, and that can be correlated with behavioural studies and psychological
      test results. Such whole organ techniques are linked to the molecular scale via
      voltage-sensitive dye (VSD) imaging studies on brain slices that provide time
      resolved images of the dynamic formation and interconnection of inter-neuronal
      complexes. The VSD experiments are readily adapted to in situ studies under high
      pressure conditions. In this tutorial review we review the current state of
      knowledge of hyperbaric effects on brain processes: anaesthesia and narcosis,
      recent studies at the molecular level via protein crystallography at high
      pressure in a Xe atmosphere, and we also present some preliminary results of VSD
      imaging of brain slices under hyperbaric conditions.

PMID- 17003896
TI  - Probing hydrogen-rich molecular systems at high pressures and temperatures.
AB  - Information on the behavior of hydrogen-containing simple molecular systems at
      high pressures and temperatures is central to many problems in chemistry and
      allied sciences. The combination of increasing pressure and temperature causes a
      redistribution of the electronic density, and the resulting alterations in
      interatomic interactions give rise to changes in macroscopic properties.
      Experimental studies of hydrogen-rich systems under extreme conditions have
      advanced considerably in recent years as a result of improvements in diamond
      anvil cell technology in combination with resistive- and laser-heating
      techniques. These experimental methods are combined with spectroscopic and
      diffraction techniques, and the results interpreted with the aid of molecular
      simulations. In this tutorial review we discuss recent findings in hydrogen,
      water, and other selected hydrogen-rich systems including compounds formed from
      these materials. The results are examined in terms of the evolution of effective
      potentials and interatomic vibrational coupling, molecular dissociation and
      recombination, ionization and polymerization, quantum effects, and order-disorder
      phenomena.

PMID- 17003897
TI  - Protein unfolding, amyloid fibril formation and configurational energy landscapes
      under high pressure conditions.
AB  - High hydrostatic pressure induces conformational changes in proteins ranging from
      compression of the molecules to loss of native structure. In this tutorial review
      we describe how the interplay between the volume change and the compressibility
      leads to pressure-induced unfolding of proteins and dissociation of amyloid
      fibrils. We also discuss the effect of pressure on protein folding and free
      energy landscapes. From a molecular viewpoint, pressure effects can be
      rationalised in terms of packing and hydration of proteins.

PMID- 17003898
TI  - High pressure solid state chemistry of carbon dioxide.
AB  - A review of experimental and theoretical studies performed over the past three
      decades on high pressure chemistry of solid CO2, at 0-80 GPa and 40-3000 K, is
      presented. Emphasis is placed on the recently discovered non-molecular covalent
      crystalline phase V, and its glassy counterpart a-CO2, along with other molecular
      phases, whose interpretation is crucial for determining the reaction path to non
      molecular CO2. The matter is still under debate, and many open issues are
      outlined, such as the true reaction mechanism for forming phase V. Finally, we
      propose arguments to stimulate possible future research in a more extended P-T
      range. This work is a tutorial review and should be of general interest both for
      solid state chemistry and condensed matter physics communities.

PMID- 17003900
TI  - High-pressure structures and phase transformations in elemental metals.
AB  - At ambient conditions the great majority of the metallic elements have simple
      crystal structures, such as face-centred or body-centred cubic, or hexagonal
      close-packed. However, when subjected to very high pressures, many of the same
      elements undergo phase transitions to low-symmetry and surprisingly complex
      structures, an increasing number of which are being found to be incommensurate.
      The present critical review describes the high-pressure behaviour of each of the
      group 1 to 16 metallic elements in detail, summarising previous work and giving
      the best present understanding of the structures and transitions at ambient
      temperature. The principal results and emerging systematics are then summarised
      and discussed.

PMID- 17003899
TI  - High-pressure studies of pharmaceutical compounds and energetic materials.
AB  - The effects of high pressure on pharmaceutical compounds and energetic materials
      can have important implications for both the properties and performance of these
      important classes of material. Pharmaceutical compounds are frequently subjected
      to pressure during processing and formulation, causing interconversion between
      solid forms that may affect properties such as solubility and bio-availability.
      Energetic materials experience extremes of both pressure and temperature under
      conditions of detonation and deflagration, causing changes in properties such as
      sensitivity to shock and chemical reactivity. This tutorial review outlines the
      various methods used to study these materials at high pressure, describes how
      pressure can be used to explore polymorphism, and provides examples of compounds
      that have been studied at high pressure.

PMID- 17003901
TI  - Structural studies and polymorphism in amorphous solids and liquids at high
      pressure.
AB  - When amorphous materials are compressed their structures are expected to change
      in response to densification. In some cases, the changes in amorphous structure
      can be discontinuous and they can even have the character of first-order phase
      transitions. This is a phenomenon referred to as polyamorphism. Most evidence for
      polyamorphic transitions between low and high density liquids or analogous
      transformations between amorphous forms of the same substance to date has been
      indirect and based on the changes in thermodynamic and other structure-related
      properties with pressure. Recent studies using advanced X-ray and neutron
      scattering methods combined with molecular dynamics simulations are now revealing
      the details of structural changes in polyamorphic systems as a function of
      pressure. Various "two state" or "two species" models are used to understand the
      anomalous densification behaviour of liquids with melting curve maxima or regions
      of negative melting slope. Thermodynamic analysis of the two state model leads to
      the possibility of low- to high-density liquid transitions caused by differences
      in bulk thermodynamic properties between different amorphous forms and on the
      degree of cooperativity between low- and high-density structural configurations.
      The potential occurrence of first-order transitions between supercooled liquids
      is identified as a critical-like phenomenon. In this tutorial review we discuss
      the background to polyamorphism, incorporating the experimental observations,
      simulation studies and the two-state models. We also describe work carried on
      several systems that are considered to be polyamorphic.

PMID- 17003902
TI  - High-pressure chemistry of nitride-based materials.
AB  - Besides temperature at one atmosphere, the applied pressure is another important
      parameter for influencing and controlling reaction pathways and final reaction
      products. This is relevant not only for the genesis of natural minerals, but also
      for synthetic chemical products and technological materials. The present critical
      review (316 references) highlights recent developments that utilise high
      pressures and high-temperatures for the synthesis of new materials with unique
      properties, such as high hardness, or interesting magnetic or optoelectronic
      features. Novel metal nitrides, oxonitrides as well as the new class of nitride
      diazenide compounds, all formed under high-pressure conditions, are highlighted.
      Pure oxides and carbides are not considered here. Moreover, syntheses under high
      pressure conditions require special equipment and preparation techniques,
      completely different from those used for conventional synthetic approaches at
      ambient pressure. Therefore, we also summarize the high-pressure techniques used
      for the synthesis of new materials on a laboratory scale. In particular, our
      attention is focused on reactive gas pressure devices with pressures between 1.2
      and 600 MPa, multi-anvil apparatus at P < 25 GPa and the diamond anvil cell,
      which allows work at pressures of 100 GPa and higher. For example, some of these
      techniques have been successfully upgraded to an industrial scale for the
      synthesis of diamond and cubic boron nitride.

PMID- 17003903
TI  - Editorial: natural products chemistry in China.
AB  - China is a country rich in plants and microbe species that cultivate a remarkable
      diversity of secondary metabolites. Such products include 'qinghaosu'
      (artemisinin) and huperzine A, which are used in the treatment of malaria and
      Alzheimer's disease, respectively.

PMID- 17003905
TI  - Diterpenoids from Isodon species and their biological activities.
AB  - Isodon species (Labiatae) are widely distributed plants, many of which are used
      in folk medicine. Over the past twenty years, they have received considerable
      phytochemical and biological attention. Thestructures of their many diterpenoids
      constituents, especially those with an ent-kaurane skeleton, have been
      elucidated. The significant phytochemical and pharmacological diterpenoids form
      the subject of this review. There are 290 references.

PMID- 17003906
TI  - Eudesmane sesquiterpenoids from the Asteraceae family.
AB  - This review covers the structures and biological activities of eudesmane-type
      sesquiterpenoids from the plants of the Asteraceae family. Biosynthetic studies
      or chemical syntheses leading to the revision of structures or stereochemistries
      have also been included, and 593 references are cited.

PMID- 17003907
TI  - Chemistry, bioactivity and geographical diversity of steroidal alkaloids from the
      Liliaceae family.
AB  - Plants belonging to the Liliaceae family have been the topic of research in many
      phytochemical and pharmacological laboratories because they contain structurally
      complex and biologically fascinating steroidal alkaloids. This review, citing 153
      references, summarises the chemistry, bioactivity and geographical diversity of
      steroidal alkaloids isolated from Veratrum and Fritillaria species, so as to
      illustrate the chemo-diversity and biological significance of these alkaloids,
      along with their geographical distribution where this is discernible.

PMID- 17003908
TI  - Biology and chemistry of endophytes.
AB  - This review focuses on new endophyte-related findings in biology and ecology, and
      also summarises the various metabolites isolated from endophytes.

PMID- 17003909
TI  - Recent progress on the total synthesis of natural products in China.
AB  - An overview of natural products synthesis in Mainland China during the past 10
      years is provided. This review only emphasizes the first total synthesis of
      molecules of contemporary interest and syntheses that helped to correct
      structures. In addition, some significant results on the novel synthesis and
      structure-activity relationship (SAR) studies of several natural products are
      introduced.

PMID- 17003910
TI  - Development and application of medicinal plant tissue cultures for production of
      drugs and herbal medicinals in China.
AB  - In the search for new drugs and natural remedies, medicinal plants or herbs used
      in folk and traditional medicines are promising candidates. For the naturally
      rare and slowly growing plant species, plant tissue culture in bioreactors
      provides a cost-effective, sustainable and well-controlled means for mass
      production of the active principles of medicinal plants, and enables fuller
      utilization of their biosynthetic capacity. Recognizing that natural resources
      and agricultural land in China are limited,many Chinese research groups have
      engaged in the development of plant tissue culture techniques and processes for
      the cultivation and rapid propagation of medicinal plants, and for the
      biosynthesis and biotransformation of phytomedicines. This review primarily aims
      to provide a comprehensive summary of the major achievements in this and related
      research areas in China over the last three decades, but also to identify the
      difficulties and predict future trends in developing plant tissue culture
      biotechnology for the manufacture of bioactive natural products.

PMID- 17003911
TI  - Antibiotic biosynthetic pathways and pathway engineering--a growing research
      field in China.
AB  - This review describes the recent research activities in China in relation to
      studies on antibiotic biosynthetic pathways and pathway engineering in
      actinomycetes. 75 references are cited.

PMID- 17003912
TI  - COX-2 inhibitors and the thrombotic risk.

PMID- 17003913
TI  - The pharmacology of selective inhibition of COX-2.
AB  - Selective inhibitors of cyclooxygenase (COX)-2 were developed to improve the
      safety of anti-inflammatory therapy in patients at elevated risk for
      gastrointestinal complications which are thought to be caused primarily by
      depression of COX-1 derived mucosal prostanoids. They were not expected to be
      more efficacious analgesics than compounds acting on both cyclooxygenases, the
      traditional (t) non-steroidal antiinflammatory drugs (NSAIDs). While these
      predictions were generally supported by clinical evidence, an elevated rate of
      severe cardiovascular complications was observed in randomized controlled trials
      of three chemically distinct COX-2 selective compounds. The cardiovascular hazard
      is plausibly explained by the depression of COX-2 dependent prostanoids formed in
      vasculature and kidney; vascular prostacyclin (PGI2) constrains the effect of
      prothrombotic and atherogenic stimuli, and renal medullary prostacyclin and
      prostaglandin (PG) E(2) formed by COX-2 contribute to arterial pressure
      homeostasis. A drug development strategy more closely linking research into the
      biology of the drug target with clinical drug development may have allowed
      earlier recognition of these mechanisms and the cardiovascular risk of COX-2
      inhibition. Open questions are i) whether the gastrointestinal benefit of COX-2
      selective compounds drugs can be conserved by identifying individuals at risk and
      excluding them from treatment; ii) whether the risk extends to tNSAIDs; iii) and
      whether alternative strategies to anti-inflammatory therapy with a more
      advantageous risk-benefit profile can be developed.

PMID- 17003914
TI  - COX-2 inhibitors and cardiovascular risk. Inferences based on biology and
      clinical studies.
AB  - Even though non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used
      for a long time, the search continues for anti-inflammatory drugs with few side
      effects. COX-2 inhibitors are currently most debated, because they have less
      gastrointestinal side effects but have been linked to increased cardiovascular
      morbidity and mortality, presumably related to thrombotic events. This has
      brought about the withdrawal of rofecoxib and other COX-2 inhibitors from the
      market. Although the results of several large studies with prospective,
      randomized design and meta-analysis of different trials have led to the demise of
      many popular COX-2 inhibitors, yet the conclusion seems to be rather simplistic.
      This review presents evidence from basic biology and clinical studies with the
      expectation that a balanced position, particularly in relation to increase in
      cardiovascular events, may be elucidated.

PMID- 17003915
TI  - Does a coxib-associated thrombotic risk limit the clinical use of the compounds
      as analgesic anti-inflammatory drugs? Arguments in favor.
AB  - Non-steroidal anti-inflammatory agents (NSAIDs) and selective cyclooxygenase (COX
      2) inhibitors (coxibs) are commonly used as analgesic and anti-inflammatory
      agents. Selective COX-2 inhibitors or coxibs were primarily developed as a
      response to the gastrointestinal toxicity of conventional NSAIDs but may have
      other side effects. Currently available data suggests definite prothrombotic risk
      with the coxibs, and the magnitude of risk may vary with individual agents. Based
      on available data, coxibs should be restricted to use as 2nd-line, possibly as
      3rd-line, agents for carefully chosen patients and randomized trials versus
      placebo or an accepted comparator must be performed to define the overall safety
      profile in diverse patient populations. The recently announced Prospective
      Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen
      (PRECISION) trial will assess the relative cardiovascular safety of three of the
      most commonly used pain relievers in the treatment of arthritis patients,
      ibuprofen, naproxen and celecoxib. The study will enroll patients with
      osteoarthritis, the most common form of arthritis, who have known coronary heart
      disease or who have multiple risk factors for heart disease and also some
      patients with rheumatoid arthritis. Patients will be followed for an average of
      two years to track the occurrence of serious cardiovascular events, including
      death, heart attack and stroke. This study should provide some definitive
      evidence of the relative cardiovascular safety of the available anti-inflammatory
      agents but would be even more useful if it included an arm where patients were
      treated with analgesics such as acetaminophen and/or moderate strength narcotics.

PMID- 17003916
TI  - Does a coxib-associated thrombotic risk limit the clinical use of the compounds
      as analgesic, antiinflammatory drugs? Arguments against.
AB  - The issue of the risk-benefit assessment of cyclooxygenase-2 (COX-2) inhibitors,
      as compared to traditional non-steroidal anti-inflammatory drugs (tNSAIDs), is
      far from being resolved. These compounds need to be carefully re-evaluated in
      order to avoid hasty conclusions, as it happened when COX-2 inhibitors were
      introduced into clinical practice. Several arguments support the concept, that
      COX-2 inhibitors remain a valuable therapeutic option at least for selected
      patients.

PMID- 17003917
TI  - Transcription-based COX-2 inhibition: a therapeutic strategy.
AB  - Potent selective cyclooxygenase-2 (COX-2) inhibitors are effective in controlling
      inflammatory disorders but are associated with cardiovascular complications.
      Their clinical use has been severely limited. We propose that transcription-based
      inhibition of COX-2 expression represents a therapeutic strategy that may
      circumvent the undesired complications of COX-2 inhibitors. Reported data from
      several laboratories including ours have identified C/EBPbeta as a key
      transactivator mediating COX-2 transcriptional activation induced by diverse pro
      inflammatory mediators. Results from our recent work show that sodium salicylate
      at pharmacological concentrations inhibits C/EBPbeta binding to COX-2 promoter by
      direct inhibition of p90 ribosomal S6 kinase (RSK). RSK phosphorylates C/EBPbeta
      and stimulates its binding to enhancer elements. We propose that RSK1/2 is a
      potential target for screening drugs with novel anti-inflammatory and anti
      neoplastic therapeutic potentials.

PMID- 17003918
TI  - Selective COX-2 inhibitors and risk of thromboembolic events - regulatory
      aspects.
AB  - In the 1990s, the pharmaceutical industry developed selective COX-2 inhibitors
      (coxibs) as alternatives to conventional nonsteroidal anti-inflammatory drugs
      (NSAIDs), with the expectation of similar analgetic and anti-inflammatory
      efficacy but a reduced risk of adverse gastrointestinal (GI) effects. Marketing
      authorisation (MA) was granted for rofecoxib and celecoxib as first
      representatives of this new pharmacological class at the end of the 1990s in the
      EU. In the following years MAs were granted for the 'second generation' coxibs
      etoricoxib, parecoxib/valdecoxib and lumiracoxib. However, data from large
      clinical 'outcome studies' as well as epidemiological data raised concerns about
      the cardiovascular (CV) safety of the coxibs. In consequence, two comprehensive
      review processes (referrals) were initiated by the European Medicines Agency
      (EMEA). As a result, in the EU the use of coxibs has been contraindicated in
      patients with established coronary heart disease, cerebrovascular disease and
      peripheral arterial disease and a number of warning statements concerning CV, GI
      and skin toxicity have been introduced in the coxib product informations. This
      article provides a description of the regulatory actions taken and discusses some
      specific aspects of the past and future regulatory assessment of coxibs.

PMID- 17003919
TI  - Evidence for the benefits of prophylaxis in the management of hemophilia A.
AB  - The optimal treatment of hemophilia has been evolving since the advent of factor
      VIII concentrates, continues to vary geographically, and remains a source of
      debate. There now exists an extensive clinical literature that demonstrates clear
      benefits of prophylaxis for patients with hemophiliaA compared to on-demand
      treatment, including a reduction in the number of bleeding episodes, improved
      joint function, and greater patient well-being. However, the value of these
      benefits must be weighed against the heavier economic burden of increased factor
      use. This paper reviews the literature that compares the benefits of prophylaxis
      with that of on-demand treatment, compares varying prophylaxis dose and
      administration frequency protocols, and considers the long-term cost-benefit of
      prophylactic therapy.

PMID- 17003920
TI  - Review on the value of graduated elastic compression stockings after deep vein
      thrombosis.
AB  - Graduated elastic compression stockings (GECS) are commonly used in the primary
      prevention of deep vein thrombosis (DVT); however, their role in preventing
      recurrent DVT and also post-thrombotic syndrome is less well established. The aim
      of this review was to investigate the effect of GECS after DVT. A literature
      search was performed by two independent searchers in order to identify randomised
      controlled trials on the effect of GECS in preventing recurrent DVT and post
      thrombotic syndrome. Four randomised trials, including 537 patients, were
      identified. Two of the studies demonstrated that below-knee GECS significantly
      reduced post-thrombotic syndrome during follow-up, while a smaller study showed
      equivocal results. GECS reduced the incidence of post-thrombotic syndrome from
      54% to 25.2% [relative risk (RR) 0.47, 95% confidence interval (CI) 0.36-0.61]
      with the number needed to treat (NNT) being 4 (95% CI 2.7-5.0). The rate of
      recurrent asymptomatic DVT was also significantly reduced by GECS (RR 0.20, 95%
      CI 0.06-0.64; NNT 5); the reduction in symptomatic DVT was not significant (RR
      0.79, 95% CI 0.50-1.26; NNT 34). In conclusion, there is level Ia evidence to
      suggest that GECS can significantly reduce the incidence of post-thrombotic
      syndrome (PTS) after DVT, and therefore these should be routinely prescribed. The
      evidence for recurrent DVT is less conclusive. Further research is needed towards
      standardising PTS diagnostic criteria and evaluating more effective preventive
      measures after DVT.

PMID- 17003921
TI  - A direct thrombin inhibitor studied by dynamic whole blood clot formation.
      Haemostatic response to ex-vivo addition of recombinant factor VIIa or activated
      prothrombin complex concentrate.
AB  - Direct thrombin inhibitors have proven efficacious in prevention of venous
      thromboembolism. Bleeding complications are rare, but in case of acute serious
      bleeding, an effective and instant haemostatic intervention may be required. In
      the present study it was demonstrated that the direct thrombin inhibitor
      melagatran induces dose-dependent abnormalities in whole blood (WB) clotting
      profiles as recorded by a recently described modified thrombelastographic model,
      and that rFVIIa or APCC are capable of improving the haemostatic capacity.
      Experiments were performed using WB from 30 healthy males. In-vitro titration
      experiments (n = 10) with addition of melagatran to WB corresponding to plasma
      concentrations ranging from 0 to 5.0 microM (12 steps) showed a dose-dependent
      prolongation of the clot initiation and characteristic decrease of the maximum
      rate of clot propagation. In-vitro intervention studies (n = 20) were completed
      with four different concentrations of melagatran as well as addition of four
      different levels of rFVIIa or APCC. At all tested concentrations of melagatran,
      rFVIIa significantly shortened the melagatran-induced prolonged clot initiation
      but induced only minor improvements of the reduced clot propagation. In contrast,
      APCC significantly and dose-dependently shortened the clot initiation and
      accelerated the clot propagation. In conclusion, our thrombelastographic model
      appears useful for evaluating the effect of direct thrombin inhibitors on
      dynamicWB clot formation and rFVIIa, but especially APCC significantly improved
      theWB clot formation. The pronounced stabilizing effect of APCC may be caused by
      its content of prothrombin and activated coagulation factors.

PMID- 17003922
TI  - In-vitro and in-vivo consequences of mutations in the von Willebrand factor
      cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a disease characterized by
      microvascular thrombosis, often associated with deficiency of the vonWillebrand
      factor (VWF) cleaving protease ADAMTS13. We investigated the spectrum of ADAMTS13
      gene mutations in patients with TTP and congenital ADAMTS13 deficiency to
      establish the consequences on ADAMTS13 processing and activity. We describe five
      missense (V88M, G1239V, R1060W, R1123C and R1219W), 1 nonsense (W1016Stop) and 1
      insertion (82_83insT) mutations. In two patients no mutation was identified
      despite undetectable protease activity. Expression in HEK293 mammalian cells
      (V88M, G1239V, R1123C and R1219W) documented that three missense mutants were not
      secreted, whereas theV88M was secreted at low levels and with reduced activity.
      We also provide evidence that impaired secretion of ADAMTS13 mutants observed in
      vitro translates into severely reduced ADAMTS13 antigen levels in patients in
      vivo. To evaluate whether the small amounts of mutant protease present in the
      circulation of patients had VWF cleaving activity, WT and mutant rADAMTS13 were
      stably expressed in Drosophila S2 cells under the influence of the Drosophila BiP
      protein signal sequence, which allows protein secretion. Drosophila expression
      system showed a 40-60% protease activity in the mutants. Several single
      nucleotide polymorphisms (SNPs) within exons and intron boundaries were found in
      patients, suggesting that the interplay of SNPs could at least in part account
      for ADAMTS13 functional abnormalities in patients without mutations. In
      conclusion, defective secretion and impaired activity of the mutants concur to
      determine an almost complete deficiency of ADAMTS13 activity in patients with a
      homozygous or two heterozygous ADAMTS13 mutations.

PMID- 17003923
TI  - Gene polymorphisms implicated in influencing susceptibility to venous and
      arterial thromboembolism: frequency distribution in a healthy German population.
AB  - Evolvement and progression of cardiovascular diseases affecting the venous and
      arterial system are influenced by a multitude of environmental and hereditary
      factors. Many of these hereditary factors consist of defined gene polymorphisms,
      such as single nucleotide polymorphisms (SNPs) or insertion-deletion
      polymorphisms, which directly or indirectly affect the hemostatic system. The
      frequencies of individual hemostatic gene polymorphisms in different normal
      populations are well defined. However, descriptions of patterns of genetic
      variability of a larger extent of different factors of hereditary
      hypercoagulability in single populations are scarce. The aim of this study was i)
      to give a detailed description of the frequencies of factors of hereditary
      thrombophilia and their combinations in a German population (n = 282) and ii) to
      compare their distributions with those reported for other regions. Variants of
      coagulation factors [factor V 1691G>A (factor V Leiden), factor V 4070A>G (factor
      V HR2 haplotype), factor VII Arg353Gln, factor XIII Val34Leu, beta-fibrinogen 
      455G>A, prothrombin 20210G>A], coagulation inhibitors [tissue factor pathway
      inhibitor 536C>T, thrombomodulin 127G>A], fibrinolytic factors [angiotensin
      converting enzyme intron 16 insertion/deletion, factor VII-activating protease
      1601G>A (FSAP Marburg I), plasminogen activator inhibitor 1-675
      insertion/deletion (5G/4G), tissue plasminogen activator intron h
      deletion/insertion], and other factors implicated in influencing susceptibility
      to thromboembolic diseases [apolipoprotein E2/E3/E4, glycoprotein Ia 807C>T,
      methylenetetrahydrofolate reductase 677C>T] were included. The distribution of
      glycoprotein Ia 807C>T deviated significantly from the Hardy-Weinberg
      equilibrium, and a comparison with previously published data indicates marked
      region and ethnicity dependent differences in the genotype distributions of some
      other factors.

PMID- 17003924
TI  - The gender-specific role of polymorphisms from the fibrinolytic, renin
      angiotensin, and bradykinin systems in determining plasma t-PA and PAI-1 levels.
AB  - Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1)
      directly influence thrombus formation and degradation and thus risk for arterial
      thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI
      1 levels in a large population-based sample from the PREVEND study in Groningen,
      the Netherlands (n = 2,527). We measured polymorphisms from genes of the
      fibrinolytic system, the renin-angiotensin system (RAS), and the bradykinin
      system. We found that males had higher levels of natural-log transformed t-PA,
      and PAI-1 (P < 0.01) compared to females. When stratifying females by menopausal
      status, PAI-1 levels were only significantly different between pre-menopausal
      females and males (p < 0.001). Furthermore, we found that age, body mass index,
      and waist-to-hip ratio were significant predictors of t-PA and PAI-1 in both
      females and males, and that the regression relationships between these factors
      and plasma t-PA and PAI-1 were dependent on gender. In addition, we found that
      the PAI-1 4G/5G polymorphism was a significant predictor of PAI-1 levels in both
      females and males, that the angiotensin II type I receptor A1166C was a
      significant predictor of t-PA and PAI-1 levels in females, and that the
      bradykinin receptor B2 58CT polymorphism was a significant predictor of t-PA
      levels in females. In conclusion, this large population-based study showed that t
      PA and PAI-1 levels are determined by several demographic and genetic factors
      involved in the fibrinolytic, RAS and bradykinin system. In addition, the results
      support the idea that the biology of t-PA and PAI-1 is different between females
      and males.

PMID- 17003925
TI  - Prognostic value of D-dimer in patients with pulmonary embolism.
AB  - D-dimer levels appear to be associated with the extent of the thromboembolic
      burden in patients with pulmonary embolism (PE). We therefore hypothesized that D
      dimer levels at admission would be associated with prospective risk of mortality
      in patients with PE. We used data from 366 patients diagnosed with PE at four
      hospital emergency departments. A highly sensitive D-dimer test was prospectively
      performed at admission. The outcome was overall mortality within three months. We
      divided patients into quartiles on the basis of their D-dimer levels and compared
      mortality rates by quartile. We estimated sensitivity, specificity, and
      predictive values for mortality in the first and fourth quartile. Overall
      mortality was 5.2%. Patients who died had higher median D-dimer levels than
      patients who survived (4578 versus 2946 microg/l; p = 0.005). Mortality increased
      with increasing D-dimer levels, rising from 1.1% in the first quartile (<1500
      microg/l) to 9.1% in the fourth quartile (>5500 microg/l) (P = 0.049).
      Sensitivity, specificity, and positive and negative predictive values of D-dimer
      levels <1500 microg/l to predict mortality were 95%, 26%, 7%, and 99%,
      respectively. Patients with PE who have D-dimer levels below 1500 microg/l have a
      very low mortality. Further studies must assess whether D-dimer, alone or
      combined with other prognostic instruments for PE, can be used to identify low
      risk patients with PE who are potential candidates for outpatient treatment or an
      abbreviated hospital stay.

PMID- 17003926
TI  - Increased red blood cell aggregation in patients with idiopathic intracranial
      hypertension. A hitherto unexplored pathophysiological pathway.
AB  - It was the objective of this study to explore the possibility that the
      aggregation of red blood cells is enhanced in individuals with increased
      intracranial hypertension (IIH). This is a prospective cross sectional
      examination in a cohort of patients with IIH and matched controls. The
      aggregation of red blood cells in the peripheral venous blood was determined by
      using a slide test and image analysis. We have presently included a group of 33
      women with IIH and the same number of women matched for age, body mass index,
      vascular risk factors and medications. A significant (p = 0.038) increment in
      fibrinogen concentrations was noted in the patients (341 +/- 60.8 mg/dl) as
      opposed to the controls 307.9 +/- 64.8). The same stands for the aggregation of
      red blood cells (aggregation parameter of 8.7 +/- 4.9 in patients vs.5.9 +/- 3.2
      in the controls, p = 0.001). We noted an increment in the aggregation of red
      blood cells in the peripheral blood of 33 women with IIH as opposed to matched
      controls. Being associated with capillary slow flow, these findings might be
      relevant to the ethiopathogenesis of this disease.

PMID- 17003927
TI  - Prevalence of thromboembolic events among 8,860 patients with thalassaemia major
      and intermedia in the Mediterranean area and Iran.
AB  - Beta-thalassaemia is a congenital haemolytic anaemia characterized by partial
      (intermedia, TI) or complete (major, TM) deficiency in the production of beta
      globin chains. The primary aim of this study was to determine the prevalence of
      thromboembolic events in patients with beta-thalassaemia. To achieve this, a
      multiple choice questionnaire was sent to 56 tertiary referral centres in eight
      countries (Lebanon, Italy, Israel, Greece, Egypt, Jordan, Saudi Arabia and Iran),
      requesting specific information on patients who had experienced a thromboembolic
      event. The study demonstrated that thromboembolic events occurred in a clinically
      relevant proportion (1.65%) of 8,860 thalassaemia patients (TI - 24.7% or TM -
      75.3%) from the Mediterranean and Iran. Thromboembolism occurred 4.38 times more
      frequently in TI than TM (p < 0.001), with more venous events occurring in TI and
      more arterial events occurring in TM. Thrombosis in thalassaemia was also more
      common in females, splenectomized patients and those with profound anaemia
      (haemoglobin <9 g/dl). Due to the increased risk of thromboembolic events, the
      rationale for splenectomy should perhaps be re-assessed and the role of
      transfusion therapy for the prophylaxis of thrombosis, among other complications,
      be evaluated prospectively.

PMID- 17003928
TI  - Low fasting methionine concentration as a novel risk factor for recurrent venous
      thrombosis.
AB  - Hyperhomocysteinemia is a risk factor for venous thrombosis, but the underlying
      mechanism is unclear. If the thiol-group of homocysteine interferes with
      components of the clotting system, we expect that high cysteine will be also a
      risk factor for venous thrombosis. If high homocysteine reflects a disturbed
      methyl-group donation by S-adenosylmethionine, we expect that low methionine will
      be a risk factor for thrombosis. We performed a case-control study in 185
      patients with recurrent venous thrombosis and in 500 control subjects. We
      determined methionine, homocysteine, cysteine and assessed the associated
      thrombotic risk. Low fasting methionine was associated with an increased risk on
      recurrent venous thrombosis [OR(bottom vs. top quartile) = 3.3 (95%CI 1.9-5.7)].
      Low methionine remained a risk factor [OR(bottom vs. top quartile) = 3.5 (95%CI
      2.0-6.0)] after adjusting for homocysteine and cysteine, whereas the thrombotic
      risk for homocysteine was lost [OR = 1.0 (95%CI 0.6-1.9)] after adjustment.
      Cysteine yielded a highest odds ratio of 2.1(top vs. bottom quartile) (95%CI 1.0
      4.0) after adjustment. In conclusion, we found that low fasting methionine is a
      risk factor for recurrent venous thrombosis. This risk association was stronger
      for methionine than for homocysteine or cysteine. This supports the hypothesis
      that impaired methylation may be involved in the pathogenesis of venous
      thrombosis.

PMID- 17003929
TI  - Potential role of activated platelets in homing of human endothelial progenitor
      cells to subendothelial matrix.
AB  - Endothelial progenitor cells (EPCs) mobilize from the bone marrow in response to
      tissue injury and participate in vascular repair. However, there is limited data
      about the homing mechanisms of EPCs to vascular injury sites. Recently animal
      experiments indicated that platelets play a role in recruitment of EPCs to injury
      sites. However, data on the possible interaction between platelets and EPCs
      within the human system are limited. We, therefore, examined in-vitro human
      platelet-EPC interaction under static and flow conditions. Human EPCs were
      isolated from donated buffy coats by magnetic microbeads and flow cytometry cell
      sorting using CD133 and VEGFR-2, respectively, as markers. Platelets were tested
      in the form of washed platelets, platelet rich plasma or whole blood. EPCs formed
      heterotypic aggregates with resting platelets under static conditions, an
      interaction that was greatly enhanced when platelets were activated by collagen,
      ADP or thrombin-activation peptide. The platelet-EPC interaction was inhibited by
      antibodies to P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1), but not by
      antibodies to glycoproteins Ib-IX-V or IIb/IIIa. When perfused over activated
      platelets under shear stress of 2.5 dyn/cm(2), EPCs tethered to platelayers and
      either adhered immediately or rolled a short distance before adhering. In
      addition, platelets promoted the colonization of adherent EPCs in culture
      conditions. Consistent with recent animal studies, these findings demonstrate
      that human EPCs interact in vitro with activated platelets under static and flow
      conditions, mediated through P-selectin-PSGL-1 interaction. This interaction may
      be a central mechanism for homing of EPCs to vascular injury sites.

PMID- 17003930
TI  - Plasma glycoprotein V levels in the general population: normal distribution,
      associated parameters and implications for clinical studies.
AB  - Soluble glycoprotein V (sGPV) is a new plasma marker of thrombosis released from
      the platelet surface by thrombin. sGPV levels are increased in patients with
      atherothrombotic diseases, but the determinants of sGPV levels are unknown in the
      general population. Identification of these potential confounding factors is
      needed for correct design and analysis of clinical studies on cardiovascular
      diseases. The aim of this study was to determine the normal range of plasma
      values and the factors controlling sGPV levels in a population of normal
      individuals. Three hundred blood donors were recruited at the Etablissement
      Francais du Sang-Alsace for the measurement of plasma levels of sGPV, platelet
      factor 4 (PF4), thrombin-antithrombin complexes (TAT) and D-dimers. The plasma
      level of sGPV was (median [interquartile range]) 27.5 [23.5-34.4] microg/l and
      displayed a Gaussian distribution. sGPV had a lower interindividual coefficient
      of variation (33%) than PF4 (176%), TAT (87%) or D-dimers (82%). sGPV levels were
      independent of age and sex but sensitive to red cell (r = 0.412; p < 0.0001) and
      platelet counts (r = 0.267; p = 0.001), total cholesterol (r = -0.313; p <
      0.0001), food intake (r = 0.184; p = 0.0014) and smoking (r = -0.154; p = 0.039).
      Contrary to PF4 and TAT, sGPV did not differ between venous and arterial blood
      samples of 12 healthy individuals. Red cell and platelet counts, total
      cholesterol, current smoking and recent food intake are important determinants of
      sGPV levels and must be taken into account in clinical studies using sGPV as a
      thrombosis marker. Normal distribution of sGPV levels in the general population
      supports its use in clinical applications.

PMID- 17003931
TI  - Plasmin/plasminogen is essential for the healing of tympanic membrane
      perforations.
AB  - Plasminogen has been proposed to play an important role in different tissue
      remodeling processes such as wound healing and tissue regeneration after
      injuries. The healing of tympanic membrane perforations is a well-organized chain
      of inflammatory events, with an initial invasion of inflammatory cells followed
      by reparative and restoration phases. Here we show that the healing of tympanic
      membrane perforations is completely arrested in plasminogen-deficient mice, with
      no signs of any healing even 143 days after perforation. Inflammatory cells were
      recruited to the wounded area, but there were no signs of tissue debridement. In
      addition, removal of fibrin, keratinocyte migration and in-growth of connective
      tissue were impaired. This contrasts with skin wound healing, where studies have
      shown that, although the healing process is delayed, it reaches completion in all
      plasminogen-deficient mice. Our finding that keratinocyte migration and re
      epithelialization were completely arrested in plasminogen-deficient mice
      indicates that plasminogen/plasmin plays a more profound role in the healing of
      tympanic membrane perforations than in the healing of other epithelial wounds.

PMID- 17003933
TI  - Elevated complement C3 is associated with early restenosis after eversion carotid
      endarterectomy.
AB  - Early restenosis following carotid endarterectomy (CEA) is an inflammatory
      process leading to myointimal hyperplasia of smooth muscle cells. The risk for
      restenosis is increased in homozygous carriers of the normal (A) allele of
      mannose-binding lectin (MBL2) gene. Our objective was to study the associations
      of C3 and as control three non-complement acute-phase reactants (APRs) (C
      reactive protein, haptoglobin and alpha2HSglycoprotein) with early restenosis
      following CEA. We also considered, whether MBL2 genotype relates to C3 levels and
      to the risk of restenosis. Concentrations of the APRs were determined by radial
      immunodiffusion or immunoturbidimetric methods in 64 patients who underwent
      eversion CEA and were followed up with carotid duplex scan (CDS) examinations for
      at least one year. MBL2 genotypes were determined by a PCR-SSP method. C3 levels
      increased during the follow-up and correlated with the percentage of restenosis
      detected by CDS at 14 months postsurgery, in MBL2 A/A allele carriers. Patients
      with high C3 levels had nearly five-fold higher odds for the presence of
      significant restenosis (>50% reduction in diameter) even after adjusting for MBL2
      genotype, age and gender. By contrast, no such associations were detected between
      the non-complement APRs and early restenosis. C3 is associated with and might
      have a direct role in the development of an early restenosis following CEA, which
      is partially related to an intact MBL lectin pathway, thus determining C3 levels
      might have clinical importance. On the other hand, our results indicate that the
      regulation of C3 differs from non-complement APRs.

PMID- 17003932
TI  - Genetic variations of the endothelial nitric oxide synthase gene are related to
      increased levels of C-reactive protein and macrophage-colony stimulating-factor
      in patients with coronary artery disease.
AB  - It was the objective of this study to investigate the relation between nitric
      oxide synthase (NOS3) gene polymorphisms, vascular inflammation, endothelial
      function, and atherosclerosis. We examined the effects of a variable nucleotide
      tandem repeats (VNTR) in intron 4, G894T in exon 7 and T-786C at the promoter
      region of NOS3 on i) C-reactive protein (CRP) and macrophage-colony stimulating
      factor (MCSF), and ii) augmentation index (AI) measured by pulse-wave analysis ,
      flow-mediated dilation (FMD) of the brachial artery, intima-media thickness (IMT)
      of the carotid and femoral artery using ultrasonography and ankle-brachial index
      (ABI) in 122 patients with chronic coronary artery disease (CAD) who underwent
      coronary angiography. MCSF and CRP were increased in patients withT-786C (77/122)
      or VNTR (40/122) allele compared to those without (F = 10.8, p = 0.002 and F =
      3.8, p = 0.04 for T-786C and F = 3.65, p = 0.04 and F = 3.2 p = 0.049 forVNTR),
      even after adjustment for traditional risk factors and medication. Patients with
      combination of VNTR and T-786C (31/122) had higher MCSF or CRP than patients with
      one or none of these alleles (p < 0.05). Among patients with T-786C, those with
      MCSF>262 pg/ml or CRP>3.2 mg/l (n = 33/77) had a higher femoral and carotid IMT
      and number of plaques in the peripheral arteries than those with lower values of
      these inflammatory indices (p < 0.05). Patients with MCSF >262 pg/ml had also
      lower FMD and higher Gensini score than those with lower MCSF (p < 0.05). The
      intron 4-VNTR and T-786C mutation of NOS3 gene enhance the inflammatory process
      in patients with chronic CAD.

PMID- 17003934
TI  - Hypofibrinogenaemia associated with common gamma82Ala-->Gly mutation is not
      mediated by altered mRNA splicing.

PMID- 17003935
TI  - A structural model of the SHBG domain of human variant protein S Heerlen.

PMID- 17003936
TI  - C-reactive protein influences shear stress-dependent platelet adhesion in
      patients with familiar hypercholesterolemia and coronary artery disease
      undergoing LDL apheresis.

PMID- 17003937
TI  - Experience of secondary prophylaxis in 20 adolescent and adult Italian
      hemophiliacs.

PMID- 17003938
TI  - Early microbial colonization of cystic fibrosis patients identified by neonatal
      screening, with emphasis on Staphylococcus aureus.
AB  - OBJECTIVES: To assess bacterial colonization prospectively in patients with
      cystic fibrosis identified by neonatal screening. To assess susceptibility to
      antimicrobials and to perform the molecular typing of Staphylococcus aureus
      strains isolated from the oropharynx of patients during the study. METHODS:
      Twenty-five cystic fibrosis patients receiving regular treatment at the Cystic
      Fibrosis Outpatient Clinic of Hospital de Clinicas of Universidade Federal do
      Parana, Brazil, were included in the study. All patients were identified by
      trypsin-like immunoreactivity and their diagnosis was confirmed by two or more
      sweat tests. Oropharyngeal swabs were collected and cultured according to routine
      methods; bacterial colonies were phenotypically identified and their
      susceptibility to antimicrobials was tested. S. aureus isolates were submitted to
      molecular typing using pulsed-field gel electrophoresis. RESULTS: Out of 234
      oropharyngeal swabs, S. aureus was the most frequently isolated strain (76% of
      patients, 42% of swabs), followed by Pseudomonas aeruginosa (36% of patients, 16%
      of swabs) and Haemophilus spp. (76% of patients; 19% of swabs). Seventy-three
      isolates were obtained from 19 patients colonized with S. aureus, of which 18
      were oxacillin-resistant (24.6%), isolated from two patients, with the same
      electrophoretic profiles as that of the Brazilian clone. The remaining oxacillin
      sensitive isolates were distributed into 18 electrophoretic profiles. CONCLUSION:
      There was higher prevalence of S. aureus, with earlier isolation than other
      pathogens. Multi-sensitive isolates were distributed into different clones,
      characterizing non-transmissibility among community-acquired strains. The
      isolated oxacillin-resistant S. aureus showed identical electrophoretic profiles,
      probably acquired in hospital. P. aeruginosa was not so frequent in the studied
      population.

PMID- 17003939
TI  - Nutritional status and anemia in Surui Indian children, Brazilian Amazon.
AB  - OBJECTIVE: To assess the nutritional status of Surui Indian children aged less
      than 10 years by means of anthropometric measurements and determination of
      hemoglobin concentration levels. METHODS: The study was carried out from February
      to March 2005 in the Sete de Setembro Indian Reservation, located on the boundary
      between the states of Rondonia and Mato Grosso, Amazonia, Brazil. Height and
      weight were measured according to standard procedures and then compared with the
      National Center for Health Statistics reference values (n = 284). Hemoglobin
      concentration was determined by a portable Beta-hemoglobinometer (Hemocue) (n =
      268). RESULTS: The percentages of children <or= -2 z scores for height for age,
      weight for age and weight for height were 25.4, 8.1 and 0%, respectively. For
      children aged less than 5 years, the percentages were 31.4, 12.4 and 0%. Most
      children had anemia (80.6%), with a rate of up to 84.0% among those aged 6 to 59
      months. CONCLUSIONS: There is a high prevalence of protein-energy undernutrition
      and anemia among Surui children. Comparison with a previous survey indicated that
      the prevalence of height for age deficit significantly decreased between 1987 and
      2005 (from 46.3 to 26.7% in children younger than 9 years). On the other hand,
      3.9% of the children were overweight in 2005, a finding that had not been
      reported in 1987. The prevalence of anemia did not change remarkably between
      these years. Despite the improvement in anthropometric parameters, the prevalence
      of nutritional deficit has been persistently higher than that observed in the
      Brazilian population at large. It is therefore necessary that systematic and
      regular monitoring of indigenous children's growth and development be
      implemented, focusing mainly on nutritional surveillance.

PMID- 17003940
TI  - Gastroduodenal peptic ulcer and Helicobacter pylori infection in children and
      adolescents.
AB  - OBJECTIVES: To show important aspects of gastroduodenal peptic ulcer and of
      Helicobacter pylori infection in children and adolescents. SOURCES: Technical
      textbooks and MEDLINE and LILACS databases including publications between 1966
      and 2006. SUMMARY OF THE FINDINGS: The etiology of peptic ulcer in children and
      adolescents may be primary, associated with H. pylori infection, or secondary, in
      which etiopathogenic mechanisms rely upon the underlying disease. The infection
      is acquired predominantly in childhood, with prevalence rates between 56.8 and
      83.1% in children who live in the poorest Brazilian regions, amounting to nearly
      10% in children aged less than 10 years in industrialized countries. The
      infection can be diagnosed by invasive methods, which investigate the presence of
      the bacterium, or of DNA, RNA or bacterial products in biopsy fragments of the
      gastric mucosa obtained at endoscopic examination; it can also be diagnosed
      through noninvasive methods, which include the detection of anti-H. pylori
      antibodies in serum, urine or saliva samples, detection of bacterial antigens in
      stool samples, and the carbon 13-labeled urea breath test. However, upper
      gastrointestinal endoscopy is the method of choice for the diagnosis of peptic
      ulcer, as it allows collecting fragments from the gastric mucosa during the
      procedure for the diagnosis of infection and for histopathological analysis.
      CONCLUSION: H. pylori infection is the major cause of peptic ulcer among
      children. Eradication of the bacterium with antimicrobial therapy results in the
      cure of the disease, and is therefore indicated for all children with H. pylori
      infection with an active, recurrent, healed, or complicated peptic ulcer.

PMID- 17003941
TI  - Use of technology as an evaluation tool of clinical care in preterm newborns.
AB  - OBJECTIVE: To assess the use of the Neonatal Therapeutic Intervention Scoring
      System (NTISS) as a tool to quantify the use of technology in neonatal intensive
      care units, in order to detect discrepancies in the care provided to high-risk
      newborn infants. METHODS: Prospective, descriptive, observational study about the
      use of technology in two neonatal intensive care units (one public and one
      private). The NTISS was calculated on a daily basis up to the discharge or death
      of preterm newborns with gestational age equal to or less than 32 weeks. We
      gathered data about prenatal clinical conditions, birth characteristics, and
      conditions on admission to the intensive care unit, as well as about the
      morbidities developed during the hospital stay. The risks of preterm newborns
      were adjusted by means of the Score for Neonatal Acute Physiology, Perinatal
      Extension, Version II (SNAPPE-II). Student's t test, chi-square test, Fisher's
      exact test, and the Mann-Whitney/Wilcoxon's test were used for the descriptive
      analysis. The study was approved by the local Research and Ethics Committee.
      RESULTS: We assessed 44 newborn infants from the public intensive care unit and
      52 from the private one. On admission, the severity score (SNAPPE-II) and the
      overall NTISS were statistically similar in both care units. The curve for the
      use of technology showed a gradual and progressive decreasing pattern in both
      care units up to the 31st day. Thereafter, there was a continuous downward trend
      in the private care unit, but a significant increase in the overall NTISS in the
      public care unit. The patients from the public care unit developed more
      morbidities than those from the private unit. CONCLUSION: Patients with similar
      clinical pictures can be treated with different levels of technological
      resources. This may have a direct impact on morbidities and on healthcare costs.
      The NTISS allowed monitoring healthcare and proved efficient in detecting
      discrepancies in practices that could influence clinical outcomes and operating
      costs.

PMID- 17003942
TI  - Consequences of bottle-feeding to the oral facial development of initially
      breastfed children.
AB  - OBJECTIVE: To identify and assess the possible consequences of bottle-feeding on
      the oral facial development of children who were breastfed up to at least six
      months of age. METHOD: Two hundred and two children (4 years of age) enrolled in
      an early health attention program participated in the study. The sample was
      divided into two groups: G1 (children who used only a cup to drink) and G2 (those
      who used a bottle). RESULTS: Lip closure was observed in 82% of the children in
      G1 and in 65% of those in G2 (p = 0.0065). The tongue coming to rest in the
      maxillary arch was found in 73% of the children in G1 and in 47% of those in G2
      (p = 0.0001). Nasal breathing was observed in 69% of G1 and in 37% of G2 (p =
      0.0001). The maxilla was shown to be normal in 90% of G1 and in 78% of G2 (p =
      0.0206). CONCLUSION: Use of the bottle, even among breastfed children interferes
      negatively with oral facial development.

PMID- 17003943
TI  - Assessment of health-related quality of life in children with functional
      defecation disorders.
AB  - OBJECTIVE: To evaluate the health-related quality of life in children with
      functional defecation disorders. METHODS: One hundred children seen consecutively
      were enrolled and subdivided into three subsets according to the Roma II
      classification criteria: functional constipation (n = 57), functional fecal
      retention (n = 29) and nonretentive functional soiling (n = 14). The generic
      instrument Child Health Questionnaire - Parent Form 50 (CHQ-PF50), was used to
      measure quality of life and to assess the impact of these disorders from the
      point of view of parents. The instrument measures physical and psychosocial
      wellbeing in 15 health domains, each of which is graded on a scale from 0 to 100,
      with higher values indicating better health and greater wellbeing. Ten of these
      are then used to obtain two aggregated and summary scores: the physical and
      psychosocial scores. RESULTS: No statistically significant differences were
      detected between subsets in terms of demographic or anthropometric
      characteristics. In 14 domains, children with defecation disorders scored lower
      than healthy children. When subsets were compared, statistically significant
      differences were detected between children with nonretentive functional soiling
      (lower scores) and those with functional constipation. Physical and psychosocial
      scores for the entire sample were lower than those for the group of healthy
      children used as controls. CONCLUSIONS: The CHQ-PF50 was considered adequate for
      demonstrating compromised quality of life in children with functional defecation
      disorders, as has been reported for other diseases, being a useful tool for
      making treatment decisions and for patient follow-up.

PMID- 17003944
TI  - Measles and rubella antibody status in children after treatment for acute
      lymphoblastic leukemia.
AB  - OBJECTIVE: To assess the vaccination history and the status of vaccine-induced
      protection from measles and rubella in children after treatment for acute
      lymphoblastic leukemia. METHODS: Measles and rubella immunological status was
      assessed by the ELISA technique for 22 children previously treated for acute
      lymphoblastic leukemia. RESULTS: From the total of 22 patients, 20 had been given
      two doses of measles vaccine and 18 had had one dose of rubella vaccine. The
      percentage of patients seropositive for measles and rubella were 65 and 88.9%,
      respectively, with no correlation with age of patient, aggression of treatment or
      the time passed between the end of treatment and sample collection. CONCLUSIONS:
      We detected that vaccination had failed against measles and rubella in 35 and
      11.1% of cases, respectively. We recommend that a measles booster be given after
      the completion of treatment for acute lymphoblastic leukemia and that rubella
      immunity status should be assessed at this point, with revaccination performed
      when necessary.

PMID- 17003945
TI  - Maximum oxygen uptake in adolescents as measured by cardiopulmonary exercise
      testing: a classification proposal.
AB  - OBJECTIVE: The identification of populational levels of maximum oxygen uptake
      (VO(2max)) is an aid to studies that propose to relate physical fitness to
      cardiovascular risk, and also for prescribing exercise and analyzing the effects
      of training. To date, there is no information with which this parameter can be
      classified in samples of adolescents from the Brazilian population. This study
      is, therefore, the first to propose the determination of mean VO(2max) levels in
      a sample of the Brazilian population. METHODS: A sample of 380 schoolchildren
      (177 boys and 203 girls, aged 10 to 14 years) was selected at random from public
      schools in Vitoria, ES. After anthropometric assessment they underwent
      cardiopulmonary exercise testing, VO(2max) was measured directly and results were
      classified according to quintiles calculated from the study sample. RESULTS: The
      mean VO(2max) values observed ranged from 42.95 to 49.55 mL x kg(-1) x min(-1)
      for boys and from 36.76 to 38.29 mL x kg(-1) x min(-1) for girls. CONCLUSION:
      This paper proposes mean VO(2max) ranges as a classification parameter for
      cardiorespiratory fitness, in addition to contributing to a definition of normal
      values for the Brazilian population. This classification will also be of use for
      establishing cutoff points in future studies.

PMID- 17003946
TI  - [Introduction to the topic: macular hole surgery].

PMID- 17003947
TI  - [Bibrocathol eye ointment is efficacious in blepharitis. Results from a
      randomized, double-blind, controlled clinical trial].
AB  - Bibrocathol (Noviform) 5% ointment is a frequently used therapy for blepharitis.
      The study included 197 patients who were randomized to be treated over 2 weeks
      with bibrocathol or an ointment vehicle, respectively. Slit lamp examinations
      were performed on day 1 (baseline) and day 14 (end of study) to assess lid edema,
      lid erythema, debris, and pouting of Meibomian glands; patients rated their
      subjective complaints. Bibrocathol was superior to the control treatment in
      improving the sum score of the 5 scales (by 7.0 vs 4.7 points, p<0.001),
      especially in patients with primarily severe symptoms (by 8.3 vs 4.8, p<0.0001).
      Antiseptic therapy with bibrocathol eye ointment 3 times daily over 2 weeks was
      found to be efficacious in the treatment of acute forms of blepharitis which do
      not require antibiotic therapy. Bibrocathol treatment is well tolerated and safe.

PMID- 17003948
TI  - [Glaucoma with unilateral reddening of the eye].

PMID- 17003949
TI  - [Selective retina therapy: methods, technique, and online dosimetry].
AB  - Selective retina therapy (SRT) is currently under evaluation, as a new and very
      subtle laser method, for the treatment of retinal disorders associated with a
      degradation of the retinal pigmentary epithelium (RPE). SRT makes it possible to
      selectively effect the RPE, sparing the adjacent neural retina with the
      photoreceptors and also the choroid below the RPE. In the best case, the therapy
      leads to regeneration of the RPE and a long-term metabolic increase at the chorio
      retinal junction. In contrast to conventional laser photocoagulation, which is
      associated with complete thermal necrosis of and around the treated site,
      absolutely no scotoma occurs in SRT. This paper reviews the methods and
      mechanisms behind the selective effects of the RPE. In vitro and preclinical
      results are used to describe the bandwidth of selective effects with respect to
      different irradiation settings. An optoacoustic technique is introduced to
      visualize effects that cannot be seen by ophthalmoscopy and to facilitate
      dosimetry control without recourse to angiography completes the report.

PMID- 17003951
TI  - Proline induces alterations in nucleotide hydrolysis in rat blood serum.
AB  - The main objective of the present study was to evaluate the in vivo (acute and
      chronic) and in vitro effects of proline on serum nucleotide hydrolysis. For
      acute administration, 29-day-old rats received one subcutaneous injection of
      proline (18.2 (micromol/g body weight) or an equivalent volume of 0.9% saline
      solution (control) and were sacrificed 1 h, 3 h or 12 h later. Results showed
      that acute proline administration provoked a decrease in ATP (42%) and ADP (49%)
      hydrolysis when rats were sacrificed 1 h after the injection. Furthermore, in
      rats killed 3 h and 12 h after acute injection, no change in nucleotide
      hydrolysis were observed. For chronic treatment, buffered proline was injected
      subcutaneously twice a day at 10 h intervals from the 6(th) to the 28(th) day of
      age. Rats were sacrificed 3 h or 12 h after the last injection. Chronic
      administration of proline did not alter the nucleotide hydrolysis when the rats
      were killed 12 h after the last injection, but decreased ATP (15%) and ADP (32%)
      hydrolysis when rats were sacrificed 3 h after the last injection. The in vitro
      effect of proline (3.0 microM - 1.0 mM) on serum nucleotide hydrolysis was also
      investigated; results showed that 1.0 mM of proline significantly increased ATP
      (45%), ADP (55%) and AMP (49%) hydrolysis. The data indicate that proline in vivo
      and in vitro alters nucleotide hydrolysis, which may be involved in the pathogeny
      of hyperprolinemic patients.

PMID- 17003950
TI  - Bradykinin-induced chloride conductance in murine proximal tubule epithelial
      cells.
AB  - Despite the recognized role of bradykinin (BK)-induced calcium and chloride
      conductance in regulating salt transport in the kidney, the signaling pathway
      involved has not been well examined. Patch clamp of murine proximal tubule
      (TKPTS) cells revealed that BK (10 nM) produced an increase in an outwardly
      rectifying current from a basal level of 2.9 +/- 0.6 to 13.8 +/- 1.1 pA/pF
      following addition of BK (n = 8; p < 0.001). The shift in reversal potential seen
      with BK on changing the intracellular solution to 152 mM chloride and significant
      inhibition of the current by 100 microM 4,4'-di-isothiocyanato-stilbene-2,2'
      disulphonic acid (DIDS) suggested that BK activated a chloride current. BK
      induced current was blocked by B2 receptor antagonist but not by B1 antagonist or
      pertussis toxin indicating that the current was mediated by B2 receptors possibly
      through Gq activation. TMB-8 completely blocked the BK-calcium rise in fura-2
      studies but did not block the BK-chloride response indicating that BK-mediated
      chloride current is calcium-independent. BK-induced current was dependent on
      phospholipase C (PLC) since U73122, a PLC-beta blocker (10 microM) blocked it
      completely. Furthermore, chloride conductance was not modulated by
      bisindolylmaleimide, an inhibitor of protein kinase C (PKC), but was enhanced by
      dibutyryl cAMP. We conclude that BK-induced rise in chloride current is mediated
      by B2 receptors and dependent on PLC activation but not dependent on calcium
      rise. Furthermore, the current can be modulated by cAMP but not PKC.

PMID- 17003952
TI  - Stabilization of membrane bound enzyme profiles and lipid peroxidation by
      Withania somnifera along with paclitaxel on benzo(a)pyrene induced experimental
      lung cancer.
AB  - The present study was aimed to evaluate the therapeutic effects of Withania
      somnifera along with paclitaxel on lung tumor induced by benzo(a)pyrene in male
      Swiss albino mice. The levels of ATPase enzymes and lipid peroxidation were
      evaluated in lung cancer bearing mice, in erythrocyte membrane and tissues. The
      extent of peroxidation was estimated by measuring the thiobarbituric acid
      reactive substances. Simultaneously the activities of different ATPases
      (Na(+)/K(+)-ATPases, Mg(2+)-ATPases and Ca(2+)-ATPases) were determined. The
      alterations of these enzyme activities in membrane and tissues were indicative of
      the tumor formation caused by benzo(a)pyrene (50 mg/kg body weight, orally) in
      cancer bearing animals. The activities of these enzymes were reversed to near
      normal control values in animals treated with Withania somnifera (400 mg/kg b.wt,
      orally) along with paclitaxel (33 mg/kg b.wt, i.p). Treatment with Withania
      somnifera along with paclitaxel altered these damage mediated through free
      radicals, and the treatment displays the protective role of these drugs by
      inhibiting free radical mediated cellular damages. Over, based on the data
      providing a correlation Withania somnifera along with paclitaxel provide
      stabilization of membrane bound enzyme profiles and decreased lipid peroxidation
      against benzo(a)pyrene induced lung cancer in mice.

PMID- 17003953
TI  - Randomized controlled trial of foot reflexology for patients with symptomatic
      idiopathic detrusor overactivity.
AB  - The aim of this study was to examine whether foot reflexology has beneficial
      effects on patients with idiopathic detrusor overactivity. One hundred and nine
      women with symptomatic idiopathic detrusor overactivity were randomized into
      either foot reflexology treatment group or nonspecific foot massage control
      group. The primary outcome measure was the change in the diurnal micturition
      frequency. There was significant change in the number of daytime frequency in the
      reflexology group when compared with the massage group (-1.90 vs -0.55, p =
      0.029). There was also a decrease in the 24-h micturition frequency in both
      groups, but the change was not statistically significant (-2.80 vs -1.04 p =
      0.055). In the reflexology group, more patients believed to have received "true"
      reflexology (88.9 vs 67.4%, p = 0.012). This reflects the difficulty of blinding
      in trials of reflexology. Larger scale studies with a better-designed control
      group and an improved blinding are required to examine if reflexology is
      effective in improving patients' overall outcome.

PMID- 17003954
TI  - Comment on Maher C, Schuessler B: "The need for randomised controlled trials in
      urogynaecology".

PMID- 17003955
TI  - Inhibition of tumour necrosis factor-alpha in patients with chronic hepatitis C
      infection.

PMID- 17003956
TI  - Schwannoma of tongue base treated with transoral carbon dioxide laser.
AB  - Schwannomas are benign slow growing solitary tumours of nerve sheath origin and
      can arise from any myelinated nerve. They have been reported to occur in most
      parts of the body with the highest incidence (25%) in the head and neck region,
      although tongue base lesions are rare. The tumour is resistant to radiotherapy,
      and therefore, the treatment of choice is surgery. We present a case of a tongue
      base schwannoma which was completely extirpated with a carbon dioxide laser via
      the transoral approach. The patient experienced virtually no morbidity from the
      use of the laser. Whilst tongue base schwannoma has been documented, we could not
      find an earlier report in the English literature describing our method of
      treatment. We conclude that transoral carbon dioxide laser can be added to the
      surgical armamentarium for the management of other similar cases in the future.

PMID- 17003957
TI  - Bronchoscopic NdYAG laser treatment in lung cancer, 30 years on: an institutional
      review.
AB  - We review our 21-year experience in bronchoscopic NdYAG laser for lung cancer and
      the relevant literature. Patients totaling 1,159 received 2,235 bronchoscopic
      treatments. The pre-requisite for laser therapy was the presence of >50%
      obstruction of the bronchial lumen. We use the rigid bronchoscope, with the
      patient under general anaesthetic and application of laser in its non-contact
      mode. Two patients (0.17%) died following the procedure, and 4.8% had non-fatal
      complications. Four to 6 weeks after treatment there was a 48% increase in
      bronchial calibre and an increase of 27% (mean) in forced vital capacity and 15%
      (mean) in forced expiratory volume in one second, respectively. These paralleled
      symptomatic relief and chest X-ray improvement. Literature review indicated
      results similar to ours in those centres with high volume activity. Thirty years
      on, bronchoscopic YAG laser therapy of lung cancer still has an important role in
      palliation of patients with inoperable lung cancer, particularly those requiring
      immediate relief of bronchial obstruction.

PMID- 17003958
TI  - Second hepatectomy for recurrent colorectal liver metastasis: analysis of
      preoperative prognostic factors.
AB  - BACKGROUND: Second hepatectomy is a potentially curative treatment for patients
      with hepatic recurrence of colorectal cancer. However, there is still no
      consensus about the patient selection criteria for second hepatectomy under these
      circumstances, and the factors affecting prognosis after second hepatectomy
      remain uncertain. METHODS: Clinicopathologic data for 111 consecutive patients
      with colorectal liver metastasis who underwent second hepatectomy at a single
      institution between 1985 and 2004, and for whom complete clinicopathologic
      reports were available, were subjected to univariate and multivariate analyses.
      RESULTS: The morbidity and mortality rates were 14% and 0%, respectively, and the
      overall 5-year survival rate was 41%. Multivariate analysis revealed that
      synchronous resection for the first liver metastasis (hazard ratio, 1.8), more
      than three tumors at the second hepatectomy (1.9), and histopathological
      involvement of the hepatic vein and/or portal vein by the first liver metastasis
      (1.7) were independently associated with poor survival. We used these three risk
      factors to devise a preoperative model for predicting survival. The 5-year
      survival rates of patients without any risk factors, and with one, two, or three
      risk factors, were 62%, 38%, 19%, and 0%, respectively. CONCLUSIONS: Second
      hepatectomy is beneficial for patients without any risk factors. Before second
      hepatectomy, chemotherapy should be considered for patients with any of these
      risk factors, especially with two or three factors, in the adjuvant or
      neoadjuvant setting to prolong survival. These results need to be confirmed and
      validated in another data set or future prospective trial according to the
      scoring scheme we outline.

PMID- 17003959
TI  - Optimum two-stage designs in case-control association studies using false
      discovery rate.
AB  - Genetic association studies using case-control designs are often done to identify
      loci associated with disease susceptibility. These studies are often expensive to
      perform, due to a large number of genetic markers. Several types of two-stage
      designs are proposed and used from the point of cost effectiveness. We proposed
      to control the false discovery rate for multiple-testing correction in two-stage
      designs, using optimal sample sizes and criteria for selecting markers associated
      with a disease in each stage to minimize the cost of genotyping. The expected
      power and cost of two-stage designs were compared with those of one-stage
      designs, under the assumptions that the genetic markers are independent and total
      sample size is fixed. The results showed that the proposed two-stage procedure
      usually reduced the cost of genotyping by 40-60%, with a power similar to that of
      the one-stage designs. In addition, the sample size and selection criteria, which
      are optimized parameters, are defined as a function of a prior probability that
      marker-disease association is true. So, the effects of mis-specification of a
      prior probability on efficiency were also considered.

PMID- 17003960
TI  - Polymorphisms of the CD14 gene and atopic phenotypes in Czech patients with IgE
      mediated allergy.
AB  - IgE-mediated allergy is a common chronic disorder resulting from interactions
      between genetic and environmental factors. The gene encoding CD14 is a positional
      candidate gene for allergic diseases as it is localised on chromosome 5q31.1, a
      region linked to asthma and bronchial hyperresponsiveness. We investigated the
      relationship among atopic phenotypes and six polymorphisms in the CD14 gene.
      Polymerase chain reaction with RFLP analyses was used to determine the CD14
      genotypes in subjects with IgE-mediated allergic diseases (n=282) and random
      controls (n=187). No significant differences in allele or genotype frequencies
      for individual polymorphisms between patients and controls were found. However,
      when atopic patients were subdivided into subjects with positive and with
      negative skin prick tests for separate antigens, T allele of the 1341G/T
      polymorphism was significantly associated with positive reactivity to mites
      (P=0.007) and moulds (P=0.041). Similarly, the C allele frequency of the -159C/T
      variant was increased in patients with positive skin prick tests for mites
      (P=0.046) and moulds (P=0.056). In haplotype analysis, the common -1619A/-1359G/
      550C/-159C/+1188G/+1341T haplotype was associated with positive reaction to these
      antigens (P values: 0.0008-0.0035). Our study supports the idea that CD14 plays a
      role in IgE-mediated allergic diseases, and its gene polymorphisms can be
      important for manifestation of these disorders.

PMID- 17003961
TI  - Application of electrokinetic instability flow for enhanced micromixing in cross
      shaped microchannel.
AB  - This paper proposes a cross-shaped micromixer featuring a pair barrier within the
      mixing channel. The proposed device obtains a rapid mixing of two sample fluids
      by means of the electrokinetic instability-induced shedding effects which are
      produced when a DC electric field of an appropriate intensity is applied. The
      proposed device uses a single high-voltage power source to simultaneously drive
      and mix the sample fluids. The effectiveness of the mixer is characterized
      experimentally as a function of the applied electric field intensity and the
      extent to which a pair barrier obstruct the mixing channel. The experimental
      results indicate that the mixing performance reaches 96% at a cross-section
      located 1 mm downstream of the cross-junction when an electric field of 300 V/cm
      is applied. The micromixing method presented in this study provides a simple low
      cost solution to mixing problems in lab-on-a-chip systems.

PMID- 17003962
TI  - Combined microfluidic-micromagnetic separation of living cells in continuous
      flow.
AB  - This paper describes a miniaturized, integrated, microfluidic device that can
      pull molecules and living cells bound to magnetic particles from one laminar flow
      path to another by applying a local magnetic field gradient, and thus selectively
      remove them from flowing biological fluids without any wash steps. To accomplish
      this, a microfabricated high-gradient magnetic field concentrator (HGMC) was
      integrated at one side of a microfluidic channel with two inlets and outlets.
      When magnetic micro- or nano-particles were introduced into one flow path, they
      remained limited to that flow stream. In contrast, when the HGMC was magnetized,
      the magnetic beads were efficiently pulled from the initial flow path into the
      collection stream, thereby cleansing the original fluid. Using this microdevice,
      living E. coli bacteria bound to magnetic nanoparticles were efficiently removed
      from flowing solutions containing densities of red blood cells similar to that
      found in blood. Because this microdevice allows large numbers of beads and cells
      to be sorted simultaneously, has no capacity limit, and does not lose separation
      efficiency as particles are removed, it may be especially useful for separations
      from blood or other clinical samples. This on-chip HGMC-microfluidic separator
      technology may potentially allow cell separations to be carried out in the field
      outside of hospitals and clinical laboratories.

PMID- 17003963
TI  - Multiscale modeling of protein transport in silicon membrane nanochannels. Part
      2. From molecular parameters to a predictive continuum diffusion model.
AB  - Transport and surface interactions of proteins in nanopore membranes play a key
      role in many processes of biomedical importance. Although the use of porous
      materials provides a large surface-to-volume ratio, the efficiency of the
      operations is often determined by transport behavior, and this is complicated by
      the fact that transport paths (i.e., the pores) are frequently of molecular
      dimensions. Under these conditions, a protein diffusion can be slower than
      predicted from Fick law. The main contribution of this paper is the development
      of a mathematical model of this phenomenon, whose parameters are computed via
      molecular modeling, as described Part 1. Our multiscale modeling methodology,
      validated by using experimental results related to the diffusion of lysozyme
      molecules, constitutes an "ab initio" recipe, for which no experimental data are
      needed to predict the protein release, and can be tailored in principle to match
      any different protein and any different surface, thus filling gap between the
      nano and the macroscale.

PMID- 17003964
TI  - Multiscale modeling of protein transport in silicon membrane nanochannels. Part
      1. Derivation of molecular parameters from computer simulations.
AB  - We report in this account our efforts in the development of a novel multiscale
      simulation tool for integrated nanosystem design, analysis and optimization based
      on a three-tiered modeling approach consisting of (i) molecular models, (ii)
      atomistic molecular dynamics simulations, and (iii) dynamical models of protein
      transport at the continuum scale. In this work we used molecular simulations for
      the analysis of lysozyme adsorption on a pure silicon surface. The molecular
      modeling procedures adopted allowed (a) to elucidate the specific mechanisms of
      interaction between the biopolymer and the silicon surface, and (b) to derive
      molecular energetic and structural parameters to be employed in the formulation
      of a mathematical model of diffusion through silicon-based nanochannel membranes,
      thus filling the existing gap between the nano--and the macroscale.

PMID- 17003965
TI  - Long-term inhibition of myocardial infarction by postconditioning during
      reperfusion.
AB  - Cardioprotection with postconditioning has been well demonstrated after a short
      period of reperfusion. This study tested the hypothesis that postconditioning
      reduces infarct size, vascular dysfunction, and neutrophil accumulation after a
      long-term reperfusion. Canines undergoing 60 min left anterior descending artery
      (LAD) occlusion were divided into two control groups of either 3 h or 24 h of
      full reperfusion and two postconditioning groups with three 30 s cycles of
      reperfusion and re-occlusion applied at the onset of either 3 h or 24 h of
      reperfusion. Size of the area at risk (AAR) and collateral blood flow during
      ischemia were similar among groups. In controls, infarct size as percentage of
      the AAR (30 +/- 3 vs. 39 +/- 2* %) by TTC staining, superoxide anion generation
      from the post-ischemic coronary arteries by lucigenin-enhanced chemiluminescence
      [(89 +/- 5 vs. 236 +/- 27* relative light units (RLU/mg)], and neutrophil (PMN)
      accumulation by immunohistochemical staining in the AAR (52 +/- 11 vs. 84 +/- 14*
      cells/mm(2) myocardium) significantly increased between 3 and 24 h of
      reperfusion. Postconditioning reduced infarct size (15 +/- 4 and 27 +/- 3.6 %),
      superoxide anion generation (24 +/- 4 and 43 +/- 11 RLU/mg), and PMN accumulation
      (19 +/- 6 and 45 +/- 8 cells/mm(2) myocardium) in the 3 and 24 h reperfusion
      groups relative to time-matched controls. These data suggest that myocardial
      injury increases with duration of reperfusion; reduction in infarct size and
      attenuation in inflammatory responses with postconditioning persist after a
      prolonged reperfusion. * p < 0.05 24 vs. 3 h control; p < 0.05 postconditioning
      vs. time-matched control.

PMID- 17003966
TI  - Gamma delta T cell receptors.
AB  - Gamma delta (gamma delta) T cells are among the least understood components of
      the immune system. While these cells appear to contribute uniquely to host immune
      competence, defining their functions in the context of host biology and pathology
      has been difficult. This is largely because it is unclear what antigens the gamma
      delta T cell receptor repertoire is directed against. During the past year, there
      have been noteworthy advances in this area. Their significance in the context of
      gamma delta T cell biology is discussed.

PMID- 17003967
TI  - [Not Available].

PMID- 17003968
TI  - [Not Available].

PMID- 17003969
TI  - [Not Available].

PMID- 17003970
TI  - [Not Available].

PMID- 17003972
TI  - [Not Available].

PMID- 17003971
TI  - [Not Available].

PMID- 17003973
TI  - [Not Available].

PMID- 17003974
TI  - [Not Available].

PMID- 17003975
TI  - [Not Available].

PMID- 17003976
TI  - [Not Available].

PMID- 17003977
TI  - [Not Available].

PMID- 17003978
TI  - [Not Available].

PMID- 17003979
TI  - [Not Available].

PMID- 17003980
TI  - [Not Available].

PMID- 17003981
TI  - [Not Available].

PMID- 17003982
TI  - [Not Available].

PMID- 17003984
TI  - [Not Available].

PMID- 17003985
TI  - [Not Available].

PMID- 17003983
TI  - [Not Available].

PMID- 17003986
TI  - [Not Available].

PMID- 17003987
TI  - [Not Available].

PMID- 17003988
TI  - [Not Available].

PMID- 17003989
TI  - [Not Available].

PMID- 17003990
TI  - [Editorial.].

PMID- 17003991
TI  - [Not Available].

PMID- 17003992
TI  - [Not Available].

PMID- 17003993
TI  - [Not Available].

PMID- 17003994
TI  - [Not Available].

PMID- 17003995
TI  - [Not Available].

PMID- 17003996
TI  - [Not Available].

PMID- 17003997
TI  - [Not Available].

PMID- 17003998
TI  - [Not Available].

PMID- 17003999
TI  - [Not Available].

PMID- 17004000
TI  - [Not Available].

PMID- 17004001
TI  - [Not Available].

PMID- 17004002
TI  - [Not Available].

PMID- 17004003
TI  - Constructing an Index for the Subjective Well-being Under Neuroleptics scale
      (SWN), short form: applying structural equation modeling for testing reliability
      and validity of the index.
AB  - Structural equation modeling (SEM) has been widely used in psychology and
      sociology for testing validity of measurement instruments. However, this
      statistical technique has so far played minor role in quality-of-life research.
      The main objective of this paper is to demonstrate the potential of SEM for
      constructing and testing the validity of a Subjective Well-being under
      Neuroleptics (SWN) index for patients with schizophrenia. For these purposes,
      data from the GEO study (Gesundheitsokonomische Evaluation von Olanzapin in
      Deutschland; Health economics study of olanzapine in the treatment of
      schizophrenia in Germany) were used. The GEO is a prospective, comparative,
      noninterventional, observational study. A total of 646 participants treated with
      either olanzapine (n = 416) or haloperidol (n = 230) were enrolled in the study;
      360 patients were available for factor analyses. The short (20-item) form of the
      SWN scale was administered to assess patients' perspectives on their quality of
      life. The structural equation models (SEMs) were then applied to construct 5- and
      10-item indexes based on SWN. The data indicate that the 5-item index is the most
      time-saving approach for evaluating perceptions of well-being (and thus, quality
      of life) among patients with schizophrenia. The application of SEM showed no
      appreciable loss of validity of this index.

PMID- 17004004
TI  - Health related quality of life after mitral valve repairs and replacements.
AB  - BACKGROUND: The decision to replace or repair mitral valves is often a difficult
      decision, and outcomes from the patients' perspective should guide decision
      making. We investigated whether the change in health related quality of life
      (HRQOL) after mitral valve surgery is different after valve repairs compared with
      replacements. METHODS: We prospectively studied 25 patients with mitral valve
      replacement and 45 patients with valve repairs performed in 1998-99. We measured
      HRQOL at baseline and at 18 months using the Medical Outcomes Trust Short Form 36
      item Health Survey (SF-36) questionnaire. We compared mean HRQOL scores of the
      groups with age-adjusted U.S. population scores. We used analysis of covariance
      to determine a change in HRQOL within groups (repair or replacement) and if the
      change in HRQOL was different between the groups. RESULTS: We found few
      differences between the groups, with more men and simultaneous coronary artery
      bypass graft surgery in the valve repair group and more prior operation in the
      valve replacement group. HRQOL improved after surgery in most domains, and was
      comparable to age-adjusted U.S. norms in the valve repair group. In the
      multivariable analysis, mitral valve repair recipients reported higher social
      functioning compared with patients who received valve replacement (p = 0.04). We
      did not find other statistically significant differences. However, the adjusted
      improvements in the component scales of physical functioning (PCS) and mental
      functioning (MCS) were substantial in the valve repair group (mean changes: PCS =
      6.8, p = 0.003; MCS = 8.1, p = 0.014) and less pronounced in the replacement
      group (mean changes: PCS = 3.6, p = 0.09; MCS = 4.3, fsp = 0.16). CONCLUSIONS:
      While many considerations influence the decision to repair or replace mitral
      valves, these findings suggest that repair may be better from the health status
      perspective. Further studies are necessary to validate this finding.

PMID- 17004005
TI  - Commentary on Cox CL, Lensing S, Rai SN et al. Proxy assessment of quality of
      life in pediatric clinical trials: application of the Health Utilities Index 3.
      Qual Life Res 2005; 14: 1045-1056.
AB  - The paper by Cox et al. offers an important potential for informing designs of
      future studies. The rates of missing measurements in the study are much greater
      than those reported by other investigators. This is not surprising because the
      nurse assessors were restricted explicitly by the study protocol from collecting
      required information, had little contact with many of the patients, and some had
      a poor understanding of the measurement system. Standard multi-attribute system
      questionnaires, such as the one used in the Cox et al. study, have been designed
      carefully and require assessments of aspects of health that are not always
      readily observable (e.g. emotional status). There is an abundance of published
      evidence, from studies conducted around the world, of acceptable measurement
      properties for these instruments. However, the published evidence also indicates
      that measurement properties are compromised with the use of proxy assessors who
      have little day-to-day knowledge of patients. We conclude that the Cox et al.
      study results provide evidence that multi-attribute system assessments should be
      elicited from patients themselves or, failing that, from proxy assessors known to
      be well-informed about the patients' capacity on all relevant attributes.

PMID- 17004006
TI  - Rational selection of an antibody probe to detect the heterogeneous collection of
      CHO-derived rhGM-CSF glycoforms.
AB  - Six anti-E. coli rhGM-CSF monoclonal antibodies were generated using hybridoma
      technology. One of these showed identical affinity for the CHO and E. coli
      derived cytokine (dissociation constants of 0.14 +/- 0.01 nM and 0.13 +/- 0.01
      nM, respectively), mapping an epitope that is not hindered by carbohydrates. The
      antibody was used to develop a simple, specific and sensitive competitive ELISA
      to quantify the entire set of rhGM-CSF glycoforms (detection limit of 780 pg/ml)
      and it was successful as an affinity ligand to purify them. Therefore, this
      particular antibody is a useful, reliable and reagent for most immunochemical
      purposes with the aim of detecting, quantifying and purifying the highly
      heterogeneous collection of the CHO-derived rhGM-CSF isoforms.

PMID- 17004007
TI  - A chromosomal investigation of some British Cantharidae (Coleoptera).
AB  - The karyotypes of 20 species of Cantharidae occurring in the British Isles are
      described and illustrated, 19 of which are hitherto unrecorded. These are
      Cantharis cryptica Ashe, Cantharis fusca Linnaeus, Cantharis lateralis Linnaeus,
      Cantharis livida Linnaeus, Cantharis nigra (Degeer), Cantharis nigricans (O. F.
      Muller), Cantharis pallida Goeze, Cantharis pellucida Fabricius, Cantharis rufa
      Linnaeus, Cantharis rustica Fallen, Cantharis thoracica (Olivier), Rhagonycha
      fulva (Scopoli), Rhagonycha lignosa (O. F. Muller), Rhagonycha limbata Thomson,
      Rhagonycha lutea (O. F. Muller), Rhagonycha testacea (Linnaeus), Silis ruficollis
      (Fabricius), Malthinus seriepunctatus Kiesenwetter, Malthodes dispar (Germar) and
      Malthodes minimus (Linnaeus). The main findings were as follows: (1) Cantharis,
      Rhagonycha and Silis have karyotypes of six pairs of autosomes plus sex
      chromosomes, which are X0 (male), XX (female). (2) Malthinus and Malthodes differ
      from the other genera in having only five pairs of autosomes. (3) The chromosome
      complement of Silis differs from those of the other genera studied in having a
      variable number of B-chromosomes in individuals from the same population. (4) The
      karyotypes of the Rhagonycha species show a degree of uniformity in the relative
      chromosome lengths, centromere positions and C-banding patterns. (5) The
      karyotypes of the Cantharis species are much more distinct from each other where
      these characteristics are concerned. (6) Maturation of the gonads takes place in
      the late larval stage. (7) The segregation of the X chromosome of Cantharis rufa
      during meiosis is pre-reductional.

PMID- 17004009
TI  - Acute concomitant pulmonary artery and aortic dissection with rupture.
AB  - Pulmonary artery (PA) dissection is uncommon and may lead to rupture and sudden
      death if encountered. A 63-year-old man presented to our emergency room with
      episodic left chest pain radiating to the back followed by shortness of breath. A
      64-row multidetector computed tomography (MDCT) revealed ruptured dissection of
      the PA and the aorta with hemopericardium, hemomediastinum, and prominent
      extravasated blood along the central bronchovascular bundles of both lungs. The
      patient experienced cardiogenic shock immediately following CT study and died
      after resuscitation. Concomitant PA and aortic dissection with rupture is
      extremely rare with the pathogenesis remaining investigated. MDCT proves to be a
      powerful tool in its diagnosis for a timely surgical repair if the patient could
      survive to have the operation.

PMID- 17004008
TI  - Anomalous origin of the right coronary artery mimicking aortic dissection at
      transesophageal echocardiography.
AB  - Transesophageal echocardiography (TEE) is the most common imaging modality for
      the detection of acute aortic syndromes. However anomalous anatomic structures
      may be occasionally misunderstood as pathologic due of lack of familiarity with
      anatomical variations; false-positive diagnosis can result, potentially leading
      to unnecessary surgical intervention. It is crucial for echocardiographers to be
      aware of possible pitfalls which may create false positive findings, since the
      complementary use of other imaging modalities, such as multislice spiral computed
      tomography (MSCT), could improve the diagnostic accuracy of TEE. We report a case
      in which an image resembling an acute aortic dissection (AAD) on transthoracic
      (TTE) and transesophageal echocardiography was found in a patient with acute
      chest pain; MSCT detected an anomalous origin of the right coronary artery as
      cause of false aortic dissection image at echocardiography.

PMID- 17004010
TI  - Congenitally corrected transposition of the great arteries: MDCT angiography
      findings and interpretation of complex coronary anatomy.
AB  - A 56-year-old male patient was admitted to our hospital because of dyspne and
      chest pain. A chest radiograph showed mild cardiomegaly. Echocardiography
      revealed unusual chamber in the heart. The chamber beneath the left atrium was
      morphologically right ventricle. To evaluate the precise complex anatomy of this
      abnormality, multidetector computed tomography (MDCT) angiography was performed.
      MDCT clearly revealed complex intracardiac and vascular anatomy, including
      typical imaging findings of a patient with congenitally corrected transposition
      of the great arteries (CCTGA). We described both imaging findings of MDCT
      angiography and interpretation of complex vascular anatomy in a patient with
      CCTGA.

PMID- 17004013
TI  - Scoring of KDR kinase inhibitors: using interaction energy as a guide for
      ranking.
AB  - Within a congeneric series of ATP-competitive KDR kinase inhibitors, we
      determined that the IC(50) values, which span four orders of magnitude,
      correlated best with the calculated ligand-protein interaction energy using the
      Merck Molecular Force Field (MMFFs(94)). Using the ligand-protein interaction
      energy as a guide, we outline a workflow to rank order virtual KDR kinase
      inhibitors prior to synthesis. When structural information of the target is
      available, the ability to score molecules a priori can be used to rationally
      select reagents. Our implementation allows one to select thousands of readily
      available reagents, enumerate compounds in multiple poses and score molecules in
      the active site of a protein within a few hours. In our experience, virtual
      library enumeration is best used when a correlation between computed
      descriptors/properties and IC(50) or K (i) values has been established.

PMID- 17004014
TI  - High-frequency Ds remobilization over multiple generations in barley facilitates
      gene tagging in large genome cereals.
AB  - Transposable elements have certain advantages over other approaches for
      identifying and determining gene function in large genome cereals. Different
      strategies have been used to exploit the maize Activator/dissociation (Ac/Ds)
      transposon system for functional genomics in heterologous species. Either large
      numbers of independent Ds insertion lines or transposants (TNPs) are generated
      and screened phenotypically, or smaller numbers of TNPs are produced, Ds
      locations mapped and remobilized for localized gene targeting. It is imperative
      to characterize key features of the system in order to utilize the latter
      strategy, which is more feasible in large genome cereals like barley and wheat.
      In barley, we generated greater than 100 single-copy Ds TNPs and determined
      remobilization frequencies of primary, secondary, and tertiary TNPs with intact
      terminal inverted repeats (TIRs); frequencies ranged from 11.8 to 17.1%. In 16%
      of TNPs that had damaged TIRs no transposition was detected among progeny of
      crosses using those TNPs as parental lines. In half of the greater than 100 TNP
      lines, the nature of flanking sequences and status of the 11 bp TIRs and 8-bp
      direct repeats were determined. BLAST searches using a gene prediction program
      revealed that 86% of TNP flanking sequences matched either known or putative
      genes, indicating preferential Ds insertion into genic regions, critical in large
      genome species. Observed remobilization frequencies of primary, secondary,
      tertiary, and quaternary TNPs, coupled with the tendency for localized Ds
      transposition, validates a saturation mutagenesis approach using Ds to tag and
      characterize genes linked to Ds in large genome cereals like barley and wheat.

PMID- 17004016
TI  - Sequential screening for diabetes--evaluation of a campaign in Swiss community
      pharmacies.
AB  - OBJECTIVE: For early detection of persons at risk for type 2 diabetes, a
      combination of risk factor assessment and glucose measurement could be a
      promising approach and an opportunity for health promotion. The object of this
      study was to develop a sequential screening concept and to evaluate it in a
      national pharmacy based screening campaign. METHOD: Community pharmacies of the
      German speaking part of Switzerland participating in the national Self Care
      campaign "Stop diabetes--test now" offered a free of charge "sequential
      screening" with (a) diabetes risk assessment, (b) consecutive capillary blood
      glucose measurement and (c) assessment of the motivation for lifestyle change
      based on the Transtheoretical Model (TTM) of behaviour change. A 35 items data
      sheet served as a structured screening protocol and enabled quick and reliable
      documentation of all relevant data. Outcomes measures were: age, sex, cigarette
      smoking, total score of the ADA diabetes risk-factor questionnaire, family
      history of diabetes, body mass index, insufficient physical activity, blood
      pressure, capillary blood glucose, motivation for lifestyle change, counselling
      activities and triage decisions of the pharmacy team. RESULTS: During the 5 weeks
      of spring 2002, 530 pharmacies screened a total of 93,258 persons (33.1% male,
      mean age 60.9 years +/- 14.1 (SD)). Risk profile: family history of diabetes
      26.4%; BMI > or = 25 kg/m(2) 49.3%; low physical activity 27.2%; elevated blood
      pressure 45.7%. Stratification into risk groups: < 2 risk factors 21.6%; > or = 2
      risk factors 71.5%; borderline glycaemia (FG 5.3-6.1 mmol/l, confirmed in a
      second measurement) 2.5% and hyperglycaemia (FG > or = 6.1 mmol/1 or NFG > or =
      11.1 mmol/1) 4.4%. Of all persons screened, 6.4% were referred to a physician and
      73.7% got targeted advice with respect to physical activity and/or nutrition
      based on their specific risk profile. CONCLUSION: The screening campaign
      attracted an important part of Swiss German speaking adults (2.4%). The
      sequential screening could successfully be implemented into pharmacy practice. Of
      the generally elderly persons screened, 6.9% were detected with suspicion for
      diabetes type 2 and 71.5% had at least two risk factors. This provided an
      opportunity to initiate targeted counselling regarding therapeutic lifestyle
      change.

PMID- 17004015
TI  - The cationic cell-wall-peroxidase having oxidation ability for polymeric
      substrate participates in the late stage of lignification of Populus alba L.
AB  - Previously we reported that purified Cell Wall Peroxidase-Cationic (CWPO-C) from
      poplar callus (Populus alba L.) oxidizes sinapyl alcohol and polymeric substrate
      unlike other plant peroxidases and proposed that this isoenzyme is a conceivable
      lignification specific peroxidase. In this study, we cloned full-length cDNA of
      CWPO-C and investigated the transcription of CWPO-C gene in various organs and
      the localization of CWPO-C protein in the differentiating xylem of poplar
      stem.Real-time PCR analyses indicated that CWPO-C gene is constitutively
      expressed in the developing xylem, leaf, and shoot but not affected by many
      stress treatments. Immunohistochemical analysis showed that CWPO-C locates in the
      middle lamellae, cell corners, and secondary cell walls of the fiber cells during
      the lignification. The intensity of the CWPO-C labeling increased gradually from
      the cell wall thickening stage to mature stage of fiber cells, which is very
      consistent with the increase of lignin content in the developing xylem. These
      results strongly support that CWPO-C is responsible for the lignification of the
      secondary xylem. Interestingly, immuno-labeling of CWPO-C was also observed
      inside of the ray parenchyma cells instead no signals were detected within the
      developing fiber cells. This suggests that CWPO-C is biosynthesized in the
      parenchyma cells and provided to the middle lamellae, the cell corners, and the
      cell walls to achieve lignin polymerization.

PMID- 17004017
TI  - Total body topical 5-fluorouracil for extensive non-melanoma skin cancer.
AB  - BACKGROUND: Topical 5-fluorouracil 5% cream is one of the treatment modalities
      for non-melanoma skin cancer (NMSC). There is a lack of suitable therapies to
      treat patients with extensive NMSC. In this paper we report two patients with
      extensive NMSC treated by total body application of topical 5-fluorouracil 5%
      cream. OBSERVATIONS: Topical 5-fluorouracil 5% cream was applied twice daily to
      the total body, including normal appearing skin. During the treatment, weekly
      blood samples were taken for measurement of 5-fluorouracil levels. All samples
      showed a 5-fluorouracil level less than the detection level of 10 microg/l. Total
      body 5- fluorouracil 5% cream was shown to be an effective treatment in our
      patients; the majority of lesions cleared in both patients. CONCLUSIONS: In
      conclusion, total body topical 5- fluorouracil 5% cream application was
      successful in two patients with extensive NMSC. No detectable serum level of 5
      fluorouracil could be determined. Pain and secondary infections were important
      side effects in our patients. However, in patients with extensive NMSC this
      treatment may be considered.

PMID- 17004018
TI  - Pharmacogenetics, the next challenge for pharmacy?
AB  - This commentary draws attention to and raises awareness of forthcoming
      pharmacogenetic technologies amongst the pharmacy profession. It aims to
      stimulate debate around the potential role that the pharmacy profession can play
      in the introduction of pharmacogenetic technologies into primary healthcare. This
      commentary discusses potential new roles for pharmacists involving
      pharmacogenetic technologies, giving attention to the way the profession may need
      to adapt to accommodate these.

PMID- 17004020
TI  - Is routine fluconazole prophylaxis necessary in preterm infants?

PMID- 17004019
TI  - Patient-centred advice is effective in improving adherence to medicines.
AB  - OBJECTIVE: To assess the effects of pharmacists giving advice to meet patients'
      needs after starting a new medicine for a chronic condition. METHOD: A
      prospective health technology assessment including a randomised controlled trial
      of a pharmacist-delivered intervention to improve adherence using a centralised
      telephone service to patients at home in England. Patients were eligible for
      recruitment if they were receiving the first prescription for a newly prescribed
      medication for a chronic condition and were 75 or older or suffering from stroke,
      cardiovascular disease, asthma, diabetes or rheumatoid arthritis. MAIN OUTCOME
      MEASURES: Incidence of non-adherence, problems with the new medicine, beliefs
      about the new medicine, safety and usefulness of the interventions. RESULTS: Five
      hundred patients consented and were randomised. At 4-week follow-up, non
      adherence was significantly lower in the intervention group compared to control
      (9% vs. 16%, P = 0.032). The number of patients reporting medicine-related
      problems was significantly lower in the intervention group compared to the
      control (23% vs. 34%, P = 0.021). Intervention group patients also had more
      positive beliefs about their new medicine, as shown by their higher score on the
      "necessity-concerns differential" (5.0 vs. 3.5, P = 0.007). The phone calls took
      a median of 12 min each. Most advice was judged by experts to be safe and
      helpful, and patients found it useful. CONCLUSION: Overall, these findings show
      benefits from pharmacists meeting patients' needs for information and advice on
      medicines, soon after starting treatment. While a substantially larger trial
      would be needed to confirm that the effect is real and sustained, these initial
      findings suggest the service may be safe and useful to patients.

PMID- 17004021
TI  - The effect of sublingual captopril versus intravenous enalaprilat on angiotensin
      II plasma levels.
AB  - A 44-year-old woman, with a history of familial adenomatous polyposis,
      complicated by carcinoma of the colon, for which a proctocolectomy had been
      performed, now presented with metastasis located in the pancreas. Treatment
      consisted of chemotherapy followed by a partial pancreaticoduodenectomy. Due to
      ischemia, resection of the small intestines was performed the same day. After
      admission, a transesophageal echocardiography showed an ejection fraction of 40%.
      Because enteral administration of drugs was impossible, intravenous enalaprilat 2
      mg once a day for 1 day followed by sublingual captopril 25 mg twice a day were
      started. Blood samples were taken before and after administration. After 1 day of
      sublingual captopril treatment the angiotensin II level decreased with more than
      50%, comparable to the decrease seen after intravenous administration of
      enalaprilat. Sublingual captopril has been used in the treatment of hypertensive
      crisis and heart failure. Although frequently reported, no study has investigated
      the effect on angiotensin II levels after sublingual administration in heart
      failure patients. This case-report demonstrated that sublingual administration of
      25 mg captopril twice a day yielded a considerable decrease in angiotensin II
      plasma levels which was comparable to the effect seen after an intravenous
      administration of 2 mg enalaprilat.

PMID- 17004022
TI  - Bacterial meningitis associated with infliximab.
AB  - We report an episode of bacterial meningitis in a 45 year-old woman, who was
      treated with infliximab for Wegener's granulomatosis. This patient presented with
      the classic clinical presentation of acute meningitis: the triad of fever, neck
      stiffness, and an altered mental state that appeared 6 months after the
      infliximab initiation. A computed tomographic (CT) scan of the head showed
      cerebral edema and Streptococcus pneumoniae was isolated from blood and CSF
      cultures. Prompt diagnosis and early treatment improved the outcome of this
      patient.

PMID- 17004023
TI  - Characteristics of drug-related problems discussed by hospital pharmacists in
      multidisciplinary teams.
AB  - OBJECTIVE: To investigate pharmacist contribution in the therapeutic hospital
      team by studying drug-related problems (DRPs), pharmacist therapy advice and
      consequences of the advice. METHODS: From May to December 2002, 827 patients in
      five Norwegian hospitals were included in the study. Demographic data, drugs
      used, relevant medical history, laboratory data and clinical/pharmacological risk
      factors were recorded prospectively at the wards. MAIN OUTCOME MEASURE: DRPs,
      patients characteristics, pharmacist advice to physicians, nurses or patients,
      response to the pharmacist advice, and reasons (stated by the pharmacist) for not
      discussing an identified DRP, were reported. An independent quality assessment
      team retrospectively assessed the DRPs for a randomly selected number of the
      study population. RESULTS: On average 2.6 DRPs per patient were found. A total of
      2128 DRPs were registered and of these 1583 (74%) DRPs were brought up for
      discussion. Physician immediate acceptance rates varied from 80% (for extremely
      important clinically significant DRPs) to 50% (for DRPs of minor clinical
      significance). High age, use of many drugs at admission, existence of many DRPs
      and many clinical/pharmacological risk factors for DRPs were associated with low
      immediate acceptance rate. Type of DRP influenced how the DRP was discussed;
      adverse drug reaction (ADR) and unnecessary drug were discussed with physicians
      while e.g. medical chart error and need for patient education were discussed with
      nurses/patients. Reasons for not discussing DRPs in the team were: not given
      priority (37%), no longer relevant (31%) and others (31%). DRPs of minor clinical
      significance were most often excluded from discussion (37%) as opposed to 14% and
      22% of those of moderate and major clinical significance. CONCLUSIONS: The
      majority of patients had one or more DRPs. The problems identified as DRPs by the
      pharmacists were accepted as such by the physicians and to a high degree acted
      upon. Both clinical significance of the DRP and patient characteristics
      influenced physician immediate acceptance rate. Some DRPs could be solved by
      direct contact with nurses or the patients. Awareness of DRPs increases through
      participation of pharmacists in the multidisciplinary therapeutic hospital team.

PMID- 17004024
TI  - Hospital inpatient self-administration of medicine programmes: a critical
      literature review.
AB  - AIM: The Department of Health, pharmaceutical and nursing bodies have advocated
      the benefits of self-administration programmes (SAPs), but their implementation
      within UK hospitals has been limited. Perceived barriers are: anticipated
      increased workload, insufficient resources and patient safety concerns. This
      review aims to discover if benefits of SAPs are supported in the literature in
      relation to risk and resource implications. METHOD: Electronic databases were
      searched up to March 2004. Published English language articles that described and
      evaluated implementation of an SAP were included. Outcomes reported were:
      compliance measures, errors, knowledge, patient satisfaction, and nursing and
      pharmacy time. RESULTS: Most of the 51 papers reviewed had methodological flaws.
      SAPs varied widely in content and structure. Twelve studies (10 controlled)
      measured compliance by tablet counts. Of 7 studies subjected to statistical
      analysis, four demonstrated a significant difference in compliance between SAP
      and controls. Eight studies (5 controlled) measured errors as an outcome. Of the
      two evaluated statistically, only one demonstrated significantly fewer medication
      errors in the SAP group than in controls. Seventeen papers (11 controlled)
      studied the effect of SAPs on patients' medication knowledge. Ten of the 11
      statistically analysed studies showed that SAP participants knew significantly
      more about some aspects of their medication than did controls. Seventeen studies
      (5 controlled), measured patient satisfaction. Two studies were statistically
      analysed and these studies suggested that patients were satisfied and preferred
      SAP. Seven papers studied pharmacy time, three studied nursing time but results
      were not compared to controls. CONCLUSIONS: The paucity of well-designed studies,
      flawed methodology and inadequate reporting in many papers make conclusions hard
      to draw. Conclusive evidence that SAPs improve compliance was not provided.
      Although patients participating in SAPs make errors, small numbers of patients
      are often responsible for a large number of errors. Whilst most studies suggest
      that SAPs increase patient's knowledge in part, it is difficult to separate out
      the effect of the educational component of many SAPs. Most patients who
      participated in SAPs were satisfied with their care and many would choose to take
      part in a SAP in the future. No studies measured the total resource requirement
      of implementing and maintaining a SAP.

PMID- 17004025
TI  - Destination, future intentions and views on practice of British-based pharmacists
      5 and 10 years after qualifying.
AB  - OBJECTIVES: The first ever Pharmacy Workforce Census of pharmacists in Great
      Britain (GB) was conducted in 2002, and repeated in 2003. Both census surveys
      aimed to gather empirical data on the employment profile of pharmacists to aid
      the workforce planning process. The aim of this paper is to compare the work
      profile and employment destination of two graduate cohorts of pharmacists to
      explore what changes take place in employment practices and how quickly they
      occur. SETTING: GB-based pharmacists. METHODS: A two-page postal questionnaire
      was sent to 38,000 GB-registered pharmacists in August 2003, to provide various
      data on employment patterns, intentions to work abroad, and desire to practise
      pharmacy. The pharmacists were contacted using addresses stored on the
      Pharmaceutical Register, a statutory record of all pharmacists and pharmacy
      premises held by the Royal Pharmaceutical Society of Great Britain (RPSGB). A sub
      set of this large data set--pharmacists who qualified in 1992 and those who
      qualified in 1997--was selected for comparison. MAIN OUTCOME MEASURE: Sector of
      employment and strength of desire to practice. RESULTS: A response rate of 75%
      was achieved for the overall census, while the response rate from the two
      graduation cohorts was 62% and 58%. Larger proportions of women compared with
      men, even after only 5 years of working as a pharmacist, are either not working
      or work part-time. Among the women, these patterns increase significantly for
      those with a greater number of years on the Pharmaceutical Register. There is
      evidence that pharmacists move out of the two main sectors of practice (hospital
      and community) with increasing years on the Register, and some gender differences
      in job mobility are observed. The School of Pharmacy from which pharmacists
      graduate appears to have some effect on practice patterns although more research
      is needed to explore this further. Desire to practise pharmacy is weaker among
      those practitioners who work in the community sector of practice, and younger
      pharmacists are more likely to intend working abroad. CONCLUSIONS: Part-time work
      patterns are implemented fairly quickly after qualifying, particularly among the
      women pharmacists. Given that female students account for over 60% of all intake
      onto pharmacy courses current supply problems will continue if work patterns
      continue along this trajectory. The ability of the profession to meet current,
      never mind extended roles, is thus called into question.

PMID- 17004026
TI  - Sales of systemic anti-infective agents in Cyprus in comparison with four other
      European countries.
AB  - OBJECTIVE: To determine the pattern of systemic antibiotic sales in Cyprus during
      the years 1990-1993 and 1996 and make a comparison with other four European
      countries. METHOD: The Anatomical Therapeutic Chemical (ATC) classification and
      the Defined Daily Dose (DDD) methodology according to the WHO (World Health
      Organization) guidelines were employed and data in wholesales were used. The
      results were presented as DDD/1000 inhabitants/day and were compared with similar
      results from Sweden, Norway, Denmark and Greece. Data from two independent
      surveys (1990 and 2001/2002), which covered a total sample of 166,979 persons
      regarding medicine taking in Cyprus were also used. RESULTS: The overall sales of
      systemic anti-infective agents in Cyprus were 22.1, 20.6, 24.5 and 24.2 DDD/1000
      inhabitants/day for 1990, 1991, 1992 and 1993 respectively. The sales number
      increased to 30.2 by 1996. Penicillins, cephalosporins and tetracyclines had the
      greatest share. The above numbers were higher than the respective ones in the
      reference countries. The first independent survey conducted in 1990 showed that
      4.2% of the population reported to take antibiotics without prescription. The
      second survey provided evidence about the kind of antibiotics taken by the sample
      (mainly amoxicillin and ciprofloxacin). CONCLUSION: These data reveal that the
      sales of antibiotics in Cyprus are higher than in Sweden, Norway, Denmark and
      Greece. The broad-spectrum antibiotics in Cyprus have higher sales than the other
      antibiotics. This study describes for the first time the pattern of systemic anti
      infective agent sales in Cyprus. Further investigations are needed in order to
      determine the possible factors that might be implicated or explain the high
      antibiotic sales in Cyprus.

PMID- 17004027
TI  - Evaluation of a short retrospective questionnaire for physical activity in women.
AB  - Physical activity (PA) is discussed as a preventive factor for many chronic
      diseases. Thus, in epidemiological studies it often is an important covariate.
      Due to frequently long latency periods, long-term PA in the past is of greater
      interest than current PA. However, there is a lack of retrospective
      questionnaires that are validated for long-term PA, including occupational,
      household, and leisure activities. We therefore evaluated a short questionnaire
      for the comprehensive assessment of usual PA in distant age periods, administered
      with cognitive interviewing techniques. From an ongoing study on postmenopausal
      breast cancer 110 cases and 101 controls, age 50-74 years, were randomly
      selected. Our questionnaire was administered in a telephone interview more than
      two months after the main study interview, which included a detailed
      questionnaire on PA performed in the age periods 30-49 years and 50+ years. Total
      PA scores were derived from both interviews as MET-hours per week. Degree of
      agreement was assessed using Bland-Altman analyses. Further, potential sources of
      systematic and random error were investigated. The mean difference between both
      questionnaires was 3 MET hours/week, and 53.6% of absolute differences were below
      35 MET hours/week, i.e. showing good agreement. Further 28.9% of differences
      could be considered acceptable agreement. Measurement errors seem to be non
      differential with respect to cancer status. The median interviewing time was 10
      min. Overall, this short questionnaire appears to be a useful and valid tool to
      distinguish between high and low levels of women's physical activity in the
      distant past.

PMID- 17004028
TI  - Rickettsial agents in Egyptian ticks collected from domestic animals.
AB  - To assess the presence of rickettsial pathogens in ticks from Egypt, we collected
      ticks from domestic and peridomestic animals between June 2002 and July 2003. DNA
      extracts from 1019 ticks were tested, using PCR and sequencing, for Anaplasma
      spp., Bartonella spp., Coxiella burnetii, Ehrlichia spp., and Rickettsia spp.
      Ticks included: 29 Argas persicus, 10 Hyalomma anatolicum anatolicum, 55 Hyalomma
      anatolicum excavatum, 174 Hyalomma dromedarii, 2 Hyalomma impeltatum, 3 Hyalomma
      marginatum rufipes, 55 unidentified nymphal Hyalomma, 625 Rhipicephalus
      (Boophilus) annulatus, 49 Rhipicephalus sanguineus, and 17 Rhipicephalus
      turanicus. Ticks were collected predominantly (>80%) from buffalo, cattle, and
      camels, with smaller numbers from chicken and rabbit sheds, sheep, foxes, a
      domestic dog, a hedgehog, and a black rat. We detected Anaplasma marginale,
      Coxiella burnetii, Rickettsia aeschlimannii, and four novel genotypes similar to:
      "Anaplasma platys," Ehrlichia canis, Ehrlichia spp. reported from Asian ticks,
      and a Rickettsiales endosymbiont of Ixodes ricinus.

PMID- 17004029
TI  - Susceptibility of Brevipalpus phoenicis to entomopathogenic fungi.
AB  - The pathogenicity of 52 isolates from several fungus species was studied for the
      false spider mite Brevipalpus phoenicis. In addition, the main stages during the
      course of infection by Hirsutella thompsonii, by far the most virulent pathogen,
      were studied by means of light and electron microscopy. Adult mites were confined
      to arenas prepared with citrus leaves in acrylic dishes containing agar-water.
      Conidial suspensions containing 10(8) conidia/ml were applied, except for H.
      thompsonii, where a concentration of 10(7) conidia/ml was used. The H. thompsonii
      isolates caused higher mortality, with indices higher than 90%. Observations
      under the scanning electron microscope (SEM) were performed at 0, 6, 12, 24, 48,
      72, and 120 h after application of a H. thompsonii suspension containing 10(7)
      conidia/ml. Twenty-four hours after inoculation, H. thompsonii conidia were
      observed attached to the mite's integument. The conidia germinated and penetrated
      through the base of the setae on the hysterosoma. Colonization occurred after 48
      h, as evidenced by mortality. Conidiogenesis occurred after 120 h, with the
      development of mycelium and conidiophores emerging from the posterior and
      anterior parts of the mite.

PMID- 17004030
TI  - Control of ticks of ruminants, with special emphasis on livestock farming systems
      in India: present and future possibilities for integrated control--a review.
AB  - India is predominantly an agricultural country with about 70% of her population
      dependent on income from agriculture. Although India accounts for a significant
      share of world's livestock resources, livestock production is greatly affected by
      ticks and tick-borne diseases (TTBDs). Therefore, India represents a particularly
      interesting scenario for the study of TTBDs. Herein, we review the problems and
      opportunities for the integrated control of ticks of ruminants with special
      emphasis on livestock farming systems in India. Developments discussed in the
      review in the area of tick vaccines and other tick control measures should have
      an impact on the future of Indian livestock production.

PMID- 17004031
TI  - Decolorization potential of mixed microbial consortia for reactive and disperse
      textile dyestuffs.
AB  - Four different aerobic mixed consortia collected from basins of wastewater
      streams coming out of dying plants of Crescent Textile (CT), Sitara Textile (ST),
      Chenab Fabrics (CF) and Noor Fatima Textile (NF), Faisalabad, Pakistan were
      applied for decolorization of Drimarene Orange K-GL, Drimarene Brilliant Red K
      4BL, Foron Yellow SE4G and Foron Blue RDGLN for 10 days using the shake flask
      technique. CT culture showed the best decolorization potential on all dyestuffs
      followed by ST, NF and CF, respectively. CT could completely decolorize all dyes
      within 3-5 days. ST cultures showed effective decolorization potential on Foron
      Yellow SE4G and Drimarene Brilliant Red K-4BL but complete color removal was
      achieved after 4 and 7 days, respectively. NF culture showed 100% decolorization
      efficiencies on Foron Yellow SE4G and Foron Blue RDGLN but it took comparatively
      longer time periods (5-7 days). Where as, the NF culture had decolorized only 40%
      and 50% of Drimarene orange and red, respectively, after 10 days. CF caused
      complete decolorization of Foron Blue RDGLN and Drimarene Brilliant Red K-4BL
      after 4 and 8 days, respectively but it showed poor performance on other two
      dyes.

PMID- 17004032
TI  - Bilateral nephron sparing surgeries for multiple renal angiomyolipomas in
      Bourneville's disease.
AB  - INTRODUCTION: Angiomyolipomas are the most common renal lesions in tuberous
      sclerosis complex. When symptomatic, the treatment includes nephron sparing
      surgery. This is especially challenging when the lesions are bilateral, large and
      multiple. CASE-HISTORY: A 22-year-old lady with bilateral multiple large
      symptomatic renal angiomyolipomas associated with other manifestations of
      tuberous sclerosis was managed with partial nephrectomies on either side. At 30
      months of follow-up, the patient has normal renal functions and no evidence of
      recurrence. DISCUSSION: Intervention for renal angiomyolipomas is indicated in
      symptomatic tumors larger than four centimetres. Selective arterial embolisation
      is the therapeutic modality of choice in such cases. However, in bilateral cases
      when angioembolisation may not always be feasible, nephron sparing surgery maybe
      considered. Nephron sparing surgery of both kidneys for angiomyolipomas in
      association with tuberous sclerosis has only been sparingly reported in
      literature.

PMID- 17004033
TI  - Prevention of membrane damage in patient on peritoneal dialysis with new
      peritoneal dialysis solutions.
AB  - Peritoneal dialysis (PD) is now an established and successful alternative to
      hemodialysis. Multiple studies have confirmed its equivalent dialysis adequacy,
      mortality and fluid balance status, at least for the first 4-5 years. Peritoneal
      membrane failure is now one of the leading cause of technique failure. This
      review describes the role of glucose, glucose degradation product, pH, lactate,
      advanced glycosylation end product (AGE) in causing this membrane damage, and
      gives insight how the use of newer peritoneal dialysis fluids (PDFs) containing
      icodextrin, amino acids and bicarbonate buffer can prevent peritoneal membrane
      damage.

PMID- 17004034
TI  - Renal lymphangiomatosis: imaging and management of a rare renal anomaly.
AB  - Renal lymphangiomatosis is a rare developmental malformation resulting in the
      development of cystic masses in the peri-pelvic or peri-renal areas. We report
      our experience in the management of this rare anomaly. Herein, we also describe
      the successful laparoscopic ablation of an uncommon subcapsular variant of renal
      lymphangiomatosis, which failed percutaneous drainage.

PMID- 17004035
TI  - Detection of tetracycline-resistant and susceptible pasteurellaceae in the
      nasopharynx of loose group-housed calves.
AB  - The aim of the present study was to determine which Pasteurella and Mannheimia
      species are present in the upper respiratory tract of healthy calves with no
      history of antimicrobial treatment prior to sampling. The presence of
      subpopulations of tetracycline-resistant Pasteurellaceae was also investigated.
      Nasal swabs from 61 loose group-housed, clinically healthy calves, 1 to 4 months
      old, from 16 dairy herds were inoculated aerobically on a selective medium
      (Columbia agar with 5% ovine blood and 16 mg/L bacitracin) with or without 4 mg/L
      oxytetracycline (OTC). A total of 43 strains belonging to the family
      Pasteurellaceae were isolated from 38 calves (62.3%) out of 13 herds (81.3%). The
      predominant organisms were Pasteurella multocida subsp. multocida (57.4%),
      Mannheimia varigena (4.9%) and M. haemolytica (3.2%). Growth of Pasteurellaceae
      on the OTC-containing medium was seen only with samples from two herds (6
      animals; 9.8%), and on only one farm this proved to be an OTC-resistant
      subpopulation. Minimum inhibitory concentration (MIC) determinations by means of
      agar dilution confirmed a low prevalence of OTC-resistant Pasteurellaceae, with
      overall MIC(50) and MIC(90) values of 0.25 and 32 mg/L, respectively. These data
      do not support the hypothesis that the relative high frequency of tetracycline
      resistant P. multocida isolates from fatal cases of bovine respiratory disease is
      related to the presence of minor tetracycline-resistance subpopulations within
      this species.

PMID- 17004036
TI  - Staphylococcus spp. abortion: skin lesions caused by Staphylococcus aureus
      infection in an aborted bovine-fetus.

PMID- 17004037
TI  - Validation of an automated spectrophotometric assay for the determination of
      cholinesterase activity in canine serum.
AB  - The determination of enzymatic activity of cholinesterase is a useful diagnostic
      method to detect exposure to anticholinesterase compounds in human and in
      veterinary medicine. We validated a modification of the Ellman method in canine
      serum and applied it to the diagnosis of dogs poisoned with anticholinesterase
      substances. The method used butyrylthiocholine as substrate and potassium
      hexacyanoferrate as chromophore. The reference range calculated on 60 clinically
      healthy dogs was set between 3405 and 6561 U/L (chi-square test for normal
      distribution, p > 0.05). The overall mean intra-assay and inter-assay
      coefficients of variation were 0.53% and 3.83%, respectively. The assay was
      linear when using two sera with 12,538 U/L and 6604 U/L serum cholinesterase
      activity (r(2) = 0.997) and 0.999, respectively). The mean recovery values of
      pooled sera with a mean pseudocholinesterase (PChE) activity of 12,081 U/L and
      pooled sera with a mean PChE activity of 3415 U/L were 103.5% and 102.8%,
      respectively. Six dogs with a diagnosis of anticholinesterase compound
      intoxication showed a decrease in cholinesterase activity of at least 50% of
      normal activity with a mean +/- SD of 487 +/- 291 U/L ranging from 169 to 847
      U/L. This technique conforms to the current standard for precision, linearity and
      accuracy and is a useful method for the complementary diagnosis of
      organophosphate or carbamate insecticide intoxication in dogs.

PMID- 17004038
TI  - Profiles of fatty acids in different bone structures of growing chicks.
AB  - This study was concerned with the dynamics of fatty acids in tissues involved in
      the growth and mineralization of the femur of Starbro chicks from 1 to 50 days of
      age. Four chickens that died of suffocation were obtained each day. Altogether,
      400 femoral bones were studied in five age groups (I-V). Compact bone, spongy
      bone and articular cartilage were sampled. Lipids were extracted according to
      Folch and fatty acids were separated using gas chromatography. The fatty acid
      profile was found to change with age. Fatty acids with the highest content in
      bone were C(18:1), C(16:0), C(18:2) and C(18:0). The highest content of fatty
      acids was found in spongy bone and the lowest in articular cartilage. Several
      correlations were revealed between individual fatty acids. The following
      conclusions were drawn. (1) Fatty acid profiles in compact bone, spongy bone and
      articular cartilage change with age of chicks. (2) Oleic (C(18:1)), palmitic
      (C(16:0)), linoleic (C(18:2)), stearic (C(18:0)) and arachidonic (C(20:4)) acids
      accounted for most of the fatty acid pool. (3) Correlations in the content of
      fatty acids were noted between bone structures.

PMID- 17004040
TI  - Pharmacokinetic-pharmacodynamic modelling of danofloxacin in turkeys.
AB  - Colibacillosis is a systemic disease responsible for important economic losses in
      poultry breeding; fluoroquinolones, including danofloxacin, are used to treat
      diseased animals. The purpose of the present study was to estimate
      pharmacokinetic-pharmacodynamic (PK-PD) surrogates for bacteriostasis,
      bactericidal activity and bacterial elimination against Escherichia coli O78/K80,
      using a PK-PD approach, for danofloxacin in turkeys after oral administration.
      Eight healthy turkeys, breed BUT 9, were included in a two-way crossover study.
      The drug was administered intravenously (i.v.) and orally at a dose rate of 6
      mg/kg bw. The values of the elimination half-life and the total body clearance
      after i.v. administration were 8.64 +/- 2.35 h and 586.76 +/- 136.67 ml kg(-1)h(
      1), respectively. After oral administration, the values of the absolute
      bioavailability and the elimination half-life were 78.37+/- 17.35% and 9.74+/-
      2.93 h, respectively. The minimum inhibitory concentration against the
      investigated strain in turkey serum was 0.25 microg/ml, four times higher than in
      broth. The lowest effective ex vivo AUC(24)/MIC ratios required for
      bacteriostasis, bactericidal activity, and total killing of E. coli O78/K80 were
      0.416 h, 1.9 h and 6.73 h, respectively. The oral dose of 6 mg/kg used in the
      present study could be interpreted as being sufficient to eliminate E. coli with
      an MIC 0.25 microg/ml. However, considering the demand that antimicrobial
      resistance should be avoided by complete bacterial elimination, PK-PD
      considerations suggest that an even higher dose of 32 mg/kg per day or 0.7
      mg/kcal per day should be evaluated in clinical trials.

PMID- 17004041
TI  - Plasma disposition and faecal excretion of netobimin metabolites and
      enantiospecific disposition of albendazole sulphoxide produced in ewes.
AB  - Netobimin (NTB) was administered orally to ewes at 20 mg/kg bodyweight. Blood and
      faecal samples were collected from 1 to 120 h post-treatment and analysed by high
      performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma
      disposition of albendazole sulphoxide (ABZSO) enantiomers produced was also
      determined. Neither NTB nor albendazole (ABZ) was present and only ABZSO and
      albendazole sulphone (ABZSO(2)) metabolites were detected in the plasma samples.
      Maximum plasma concentrations (C(max)) of ABZSO (4.1 +/- 0.7 microg/ml) and
      ABZSO(2) (1.1 +/- 0.4 microg/ml) were detected at (t(max)) 14.7 and 23.8 h,
      respectively following oral administration of netobimin. The area under the curve
      (AUC) of ABZSO (103.8 +/- 22.8 (microg h)/ml) was significantly higher than that
      ABZSO(2)(26.3 +/- 10.1 (microg h)/ml) (p < 0.01). (-)-ABZSO and (+)-ABZSO
      enantiomers were never in racemate proportions in plasma. The AUC of (+)-ABZSO
      (87.8 +/- 20.3 (microg h)/ml) was almost 6 times larger than that of (-)-ABZSO
      (15.5 +/- 5.1 (microg h)/ml) (p < 0.001). Netobimin was not detected, and ABZ was
      predominant and its AUC was significantly higher than that of ABZSO and ABZSO(2),
      following NTB administration in faecal samples (p > 0.01). Unlike in the plasma
      samples, the proportions of the enantiomers of ABZSO were close to racemic and
      the ratio of the faecal AUC of (-)-ABZSO (172.22 +/- 57.6 (microg h)/g) and (+)
      ABZSO (187.19 +/- 63.4 (microg h)/g) was 0.92. It is concluded that NTB is
      completely converted to ABZ by the gastrointestinal flora and absorbed ABZ is
      completely metabolized to its sulphoxide and sulphone metabolites by first-pass
      effects. The specific behaviour of the two enantiomers probably reflects
      different enantioselectivity of the enzymatic systems of the liver that are
      responsible for sulphoxidation and sulphonation of ABZ.

PMID- 17004039
TI  - The role of exogenous insulin in the complex of hepatic lipidosis and ketosis
      associated with insulin resistance phenomenon in postpartum dairy cattle.
AB  - As a result of a marked decline in dry matter intake (DMI) prior to parturition
      and a slow rate of increase in DMI relative to milk production after parturition,
      dairy cattle experience a negative energy balance. Changes in nutritional and
      metabolic status during the periparturient period predispose dairy cattle to
      develop hepatic lipidosis and ketosis. The metabolic profile during early
      lactation includes low concentrations of serum insulin, plasma glucose, and liver
      glycogen and high concentrations of serum glucagon, adrenaline, growth hormone,
      plasma beta-hydroxybutyrate and non-esterified fatty acids, and liver
      triglyceride. Moreover, during late gestation and early lactation, flow of
      nutrients to fetus and mammary tissues are accorded a high degree of metabolic
      priority. This priority coincides with lowered responsiveness and sensitivity of
      extrahepatic tissues to insulin, which presumably plays a key role in development
      of hepatic lipidosis and ketosis. Hepatic lipidosis and ketosis compromise
      production, immune function, and fertility. Cows with hepatic lipidosis and
      ketosis have low tissue responsiveness to insulin owing to ketoacidosis. Insulin
      has numerous roles in metabolism of carbohydrates, lipids and proteins. Insulin
      is an anabolic hormone and acts to preserve nutrients as well as being a potent
      feed intake regulator. In addition to the major replacement therapy to alleviate
      severity of negative energy balance, administration of insulin with concomitant
      delivery of dextrose increases efficiency of treatment for hepatic lipidosis and
      ketosis. However, data on use of insulin to prevent these lipid-related metabolic
      disorders are limited and it should be investigated.

PMID- 17004042
TI  - Chronic vanadium poisoning in calves and its treatment with calcium disodium
      ethylenediaminetetraacetate.
AB  - Sixteen Friesland heifer calves aged between 96 and 157 days were removed from a
      dairy farm that had been polluted with vanadium and randomly allocated into two
      equal groups (n = 8). The objective of the trial was to determine whether calcium
      disodium ethylenediaminetetraacetate (CaNa(2)EDTA) could be used as a treatment
      for cattle running in environments high in background vanadium. The treatment
      group received 80 mg CaNa(2)EDTA per kg body weight intraperitonealy (i.p.) twice
      a week over a 10-week period. The control group received normal saline i.p. over
      the same period. During the trial calves were exposed to a daily intake of
      vanadium in the form of contaminated tef hay derived from the farm of origin. In
      addition, the total mixed ration was spiked with a further 20 mg V(2)O(5)/kg feed
      to compensate for possible on-farm inhalation exposure. A stochastic model was
      used to estimate daily intake of vanadium as a distribution function. The model
      estimated that the daily intake of vanadium varied between an absolute minimum of
      33 mg/day to an absolute maximum of 124 mg/day. The average intake of vanadium
      was 71.8 mg per day per calf. Various chemical pathology parameters were measured
      throughout the trial as well as urine excretion rates of vanadium and lymphocyte
      stimulation counts. All calves were slaughtered and necropsied in cohorts of 4-6
      animals at monthly intervals after completion of the trial and withdrawal of
      vanadium from the ration. Tissue concentrations of vanadium were determined and
      necropsy findings were noted. The study found that CaNa(2)EDTA appears to enhance
      the excretion of vanadium in calves, but could not prove that the treatment had a
      protective effect against vanadium exposure. Calves were able to tolerate the
      prolonged treatment with CaNa(2)EDTA without side-effects.

PMID- 17004043
TI  - Influence of grain processing on acid-base balance in feedlot steers.
AB  - Grain processing (e.g. grinding, steaming, pelleting, flaking) has been reported
      to modify the incidence of ruminal disturbances in feedlot cattle. This study
      investigated the effects of two grain processing methods widely used in Spanish
      feedlots (grinding and pelleting) on animal performance, blood acid-base balance,
      blood electrolyte levels and serum lactate in a 140-day feedlot experiment with
      double-muscled Belgian Blue steers. The main aim of the study was to evaluate the
      way in which these two feeds modify blood acid-base balance, which is closely
      associated with ruminal pH. In light of our results we conclude that the animals
      that received the pelleted feed showed a more stable acid-base balance over time
      than those fed a ground feed. Nevertheless, higher levels of L-lactate and lower
      base excess (BE) and HCO(3)(-) values for cattle fed pelleted grain reflect a
      greater risk of grain-acid overload.

PMID- 17004044
TI  - [What advantages does volar plate fixation have over K-wire fixation for distal
      radius extension fractures in the elderly?].
AB  - PURPOSE: The purpose of this retrospective study was to compare the outcome of
      open reduction and internal fixation (ORIF) followed immediately by physiotherapy
      and of percutaneous K-wire-fixation and casting for unstable distal radius
      fractures in elderly patients, considering the results both in general, for all
      such fractures, and selectively for A3 and C2 fractures. METHODS: Follow-up
      examinations were performed 26 (18-48) months after surgery in 43 patients
      (median age 67 (60-83) years) treated with K-wire fixation and 9 (5-17) months
      after surgery in 46 patients (median age 76 (60-90) years) treated with ORIF, and
      the outcome of each was recorded as Disabilities of the Arm, Shoulder and Hand
      (DASH), Gartland-Werley and Castaing scores; the radiological loss of correction
      was also assessed. Statistical analysis was performed first without reference to
      the specific type of fracture for the K-wire- and the total ORIF -groups, and
      then selectively for A3 and C2 -fractures only; in the second analysis the
      patients were divided into three groups: KD, ORIF with and ORIF without angular
      stability. RESULTS: The Garland-Werley and Castaing scores do not indicate any
      significant difference between the procedures specified. According to the Garland
      Werley score 37 patients (86%) treated by K-wire fixation and 39 (85%) treated by
      ORIF achieved "excellent" and "good" results; according to the Castaing score
      there were 33 (77%) "good" results after K-wire fixation and 34 (74%) good
      results after ORIF. The radiological loss of correction (K-wire fixation/ORIF) as
      measured by the radial inclination (median 2/2.5 degrees), the palmar tilt
      (median 3/5 degrees) and the radial shortening (median 1/1 degrees mm) do not
      differ significantly. Suboptimal radiological results do not always correlate
      with results that are only "fair" or "poor". The non-fracture-specific DASH score
      suggests a higher degree of patient satisfaction after K-wire fixation (7 [0-87]
      points) than after ORIF (17 [0-82] points), which is not confirmed by fracture
      specific evaluation. There is a significantly earlier return to the "activities
      of daily living" (4 as against 8 weeks) after ORIF. CONCLUSION: All the
      treatments compared are suitable for the treatment of A3 and C2 fractures. The
      important advantages of ORIF are the early functional physiotherapy without
      casting and without obligatory second surgery and the earlier return to
      "activities of daily living", which are all of decisive importance for older
      patients, who are the ones most frequently affected.

PMID- 17004045
TI  - [A new parallel drill guide for navigating femoral neck screw placement.
      Development and evaluation].
AB  - BACKGROUND: Trauma navigation applications employ conventional mechanical
      surgical instruments for the simulation of drilling trajectories. Few complex
      mechanical targeting instruments, such as guides with fixed angles or with
      multiple parallel cannulas, have been adapted into trauma navigation systems. We
      have integrated a complex mechanical tool, the parallel drill guide (PDG) for the
      minimally invasive treatment of femoral neck fractures, into a trauma navigation
      module. The combined advantage of a complex yet commonly used mechanical tool
      with the benefits of fluoroscopic navigation was evaluated. MATERIAL AND METHODS:
      To adapt the conventional PDG to a fluoroscopic navigation system, the instrument
      was fitted with a non-detachable reflective marker array. Navigation engineers
      developed custom software to enable visualization of the navigated PDG. A
      comparison of conventional versus navigated PDG techniques was performed on
      plastic bone models and cadavers. No software or mechanical failures occurred
      with the navigated PDG procedures. RESULTS: While the total operative time was
      30% more with navigation compared with conventional techniques, the total
      radiation time for the navigated group was reduced by more than 60%. This study
      demonstrates the successful integration of a cannulated parallel drill guide with
      a fluoroscopic navigation system. CONCLUSION: The continuous display of the
      complex PDG mechanical instrument, with multiple parallel virtual trajectories,
      enables safe and accurate parallel screw placement. The integration of complex
      mechanical instrumentation with navigation for the accurate placement of hardware
      represents an attractive direction in multiple trauma applications.

PMID- 17004046
TI  - [Distal intraarticular humerus fractures in elderly patients. Treatment with
      combined percutaneous screw fixation and an external fixator].
AB  - BACKGROUND: Intra-articular distal humerus fractures are relatively uncommon. Due
      to osteoporosis in elderly patients, stable fixation still remains a problem
      despite new implants providing angular stability. MATERIAL AND METHODS: The
      treatment of choice is open reduction and plate fixation requiring an extended
      approach with olecranon osteotomy often combined with additional postoperative
      immobilisation in a long arm cast. We describe a technique using closed reduction
      and percutaneous osteosynthesis with cannulated screws combined with external
      fixation. Morbidity due to surgical exposure and potential risks are diminished
      while functional results are comparable to open reduction and internal fixation .
      In contrast to plasters or casts, the use of an external fixator allows stable
      and safety protection of the elbow joint, preserving wrist function as well as
      forearm rotation and increasing the patient's comfort during immobilisation.
      RESULTS: We have used this technique on ten patients aged 76.2 years (range 67-88
      years). According to the AO classification, there were three B-1/B-2 fractures,
      four C-1 and three C-2/C-3 fractures without severe comminution. The duration of
      external fixation was 6.3 weeks (range 4-8 weeks) before fracture union was
      achieved. This allows the initiation of physiotherapy and motion of the elbow.
      There was only one revision caused by the necessary replacement of an aseptic
      loosened Schanz screw. At follow-up 3 months postoperatively, the range of motion
      of the elbow was 95 degrees (65 degrees-105 degrees ), average extension 25
      degrees (10 degrees-35 degrees ) and mean flexion was 115 degrees (100 degrees
      120 degrees ) with all patients exhibiting full pro/supination.

PMID- 17004047
TI  - [Analysis of burn treatment for children at Bochum University Hospital].
AB  - BACKGROUND: A retrospective epidemiological multifactorial study of pediatric
      burn patients admitted to the Burn Center Bochum in the period of 1992-2002 was
      performed. METHODS: Data from 628 patients were analyzed and included age, sex,
      mortality, hospital stay, percent of total body surface area (TBSA) burned,
      localization of burns, number of surgical procedures, source of the burn as well
      as social standing of the families. RESULTS: The majority of patients (414) were
      between 0 and 3 years. The median age was 2.99. The median TBSA was 11.9%. There
      were 387 males (62%) and 241 females (38%, ratio of 1.6:1). The overall mortality
      rate was 1.4% (6/629). The main causes of injury were scald burns (435; 70%),
      followed by flame burns (153; 24%), electric injuries (17; 3%), and hot oil (21;
      3%). Surgery was performed on 365 (58%) children. The others (263; 42%) were
      treated without surgery. DISCUSSION: The number of children with a background
      other than German was higher; moreover, a high number of injuries was not covered
      by health insurance. Having identified the high-risk group among the pediatric
      burn patients, we suggest that prevention programs should be directed towards
      these families in order to reduce further risk of pediatric burns.

PMID- 17004048
TI  - Microhabitat selection in the simple oribatid community dwelling in epilithic
      moss cover (Acari: Oribatida).
AB  - The moss cover of a roof was studied as the model of a simple habitat divided
      into microhabitats by the members of a community of saprophagous mites. This
      community consisted of two species of oribatid mites: Scutovertex minutus and
      Trichoribates trimaculatus. They were extracted from moss onto moist paper, and
      subsequently, their mobility, responses to moisture fluctuation, and food
      selection were tested in laboratory experiments. For the nutritional biology, the
      microanatomy of their alimentary tract was examined according to the system of
      histological characteristics formulated in the laboratory of the author (type of
      food, digestive activity of gut walls, etc.). The paraplast sections of the mites
      were stained by Masson triple stain for these purposes. Moreover, the
      enzymological tests (chitinase and cellulase activities) were performed to detail
      the digestive processes. Such an approach was applied to field-sampled specimens
      as well as to those in the laboratory experiments. These above-mentioned data
      were discussed with respect to microhabitat selection, vertical and horizontal
      distribution, and dispersal ability of these two oribatid mites sharing this
      habitat. These two species differ in several characteristics from each other and
      these differences resulted in their different microhabitat choices and role in
      the habitat as a whole.

PMID- 17004049
TI  - [A comparison of respiratory muscle strength, pulmonary function tests and
      endurance in patients with early and late stage ankylosing spodylitis].
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a multisystemic disease in which
      pulmonary function is altered owing mainly to the restriction of chest wall
      involvement. A restrictive ventilatory defect has been extensively reported. This
      has been suggested to be a consequence of reduced mobility of the thoracic cage.
      Respiratory function in AS shows a typical restrictive pattern but pulmonary
      compliance, diffusion capacity, and arterial blood gases are normal. OBJECTIVE:
      The objective of the present study was to compare pulmonary function tests (PFT),
      respiratory muscle strength (MIP, MEP) and endurance (MVV) in early and late AS.
      METHODS: A total of 35 patients (30 males, 5 females) took part, all of whom met
      the New York criteria for AS. Patients were divided into two groups for the
      comparison of early (disease duration <10 years, 20 patients) and late (disease
      duration >10 years, 15 patients) manifestations in pulmonary function tests,
      respiratory muscle strength and endurance, dyspnea score, chest expansion, and
      BASFI score. In addition, 21 healthy controls were compared with the AS patients.
      Measurement of chest expansion was performed in all subjects. Pulmonary function
      tests were performed by spirometry. Respiratory muscle strength was evaluated by
      a mouth pressure meter (MPM). Functional status was assessed by BASFI in all AS
      patients. RESULTS: There was no significant difference in body mass index between
      the groups. The FVC and FEV(1) were significantly lower in late AS (p=0.003,
      p=0.03, restrictive ventilatory defect ). Chest expansion was significantly lower
      in late AS (p<0.05). There was no significant difference for MIP or MEP values
      between late AS, early AS and the controls (p>0.05). Endurance (MVV) was
      significantly lower in late AS patients (p=0.05). Although the BASFI and dyspnea
      scores were higher in late AS, they did not reach significant levels. In
      addition, age was negatively correlated with MIP and MEP in late AS (r=-0.733;
      p=0.02, r=-0.667; p=0.05). CONCLUSION: This study demonstrates that FVC and
      FEV(1) (hallmarks of a restrictive pattern), MVV (endurance) and chest expansion
      are especially involved in long-standing AS. Therefore, improvement of the
      thoracic cage should be taken into consideration, especially in early AS. These
      patients should be encouraged to make regular respiratory exercises for
      preventing the limitation of chest expansion and also improving cardiopulmonary
      fitness and respiratory endurance.

PMID- 17004050
TI  - [Link between rheumatoid arthritis and cancer].
AB  - Because it is a systemic disorder, rheumatoid arthritis (RA) is known to
      predispose affected individuals to other organ manifestations as well as
      arthritic problems. The serious complications include pericarditis, pulmonary and
      cutaneous nodules, episcleritis, and rheumatoid vasculitis. Of late, a
      significantly increased incidence of lymphoma has also accumulated. The overall
      risk is about double than in the general population, but that in patients with
      the most severe arthritis is dramatically higher. Men with RA appear to have an
      extremely elevated risk of Hodgkin's disease, which has also been observed at a
      higher incidence among the children of affected patients. These lymphomas are not
      typically infected with EBV, though RA patients have a defective capacity to
      control systemic EBV infection. Increasing attention is being paid to the effect
      of RA treatments on development of lymphoma, and some patients with EBV-positive
      tumors who have been taking methotrexate have shown a positive response after
      just discontinuing this drug. More controversial is the question of whether anti
      TNF alpha agents involve an increased risk of lymphoma; in light of the
      conflicting evidence this matter is still unresolved.

PMID- 17004051
TI  - [Sjogren's syndrome. Current aspects from a rheumatological point of view].
AB  - Sjogren's syndrome is an autoimmune disease of the exocrine glands characterized
      by the leading symptoms of keratoconjunctivitis and stomatitis sicca based on a
      complex pathogenesis. The prevalence is about 0.5-1%; primary Sjogren's syndrome
      is differentiated from secondary Sjogren's syndrome associated with other
      autoimmune disorders. The diagnosis is established by the presence of subjective
      complaints and objective evidence of sicca symptoms, anti-Ro(SSA)/La(SSB)
      antibodies, and/or focal lymphocytic infiltration of the glandular tissue. In
      addition to the typical sicca symptomatology, which is managed symptomatically by
      substitution and stimulation therapy, some patients exhibit extraglandular
      manifestations. Complaints involving the musculoskeletal system and inner ear
      dominate and are treated by the rheumatologist. The indication for base therapy
      is tailored to individual needs, but the efficacy of this approach has not been
      established in studies. About 5-10% of the patients with primary Sjogren's
      syndrome develop a B-cell non-Hodgkin's lymphoma. The disease requires
      interdisciplinary management including, among others, ophthalmologists, dentists,
      and otorhinolaryngologists, depending on the clinical picture.

PMID- 17004052
TI  - Formation of extracellular polymeric substances from acidogenic sludge in H2
      producing process.
AB  - In this study, the formation of extracellular polymeric substances (EPS) and
      surface characteristics of an acidogenic sludge in anaerobic H(2)-producing
      process was investigated. Results show that carbohydrates, proteins, and humic
      substances were the dominant components in bound EPS (BEPS), while in soluble EPS
      (SEPS), carbohydrates were the main component. The total content of BEPS
      initially increased but then kept almost unchanged during fermentation from 25 to
      35 h; after that, it slightly decreased. The total content of SEPS increased to
      172.5 +/- 0.05 mg C g(-1) volatile suspended solid with the time that increased
      to 23.5 h, and then rapidly decreased until 43 h; thereafter, it kept almost
      unchanged. The SEPS had good correlations with the specific H(2) production rate,
      substrate degradation rate, and specific aqueous products formation rate, but the
      BEPS seemed to have no such correlations with these specific rates. Results also
      confirm that part of EPS could be utilized by the H(2)-producing sludge. As the
      substrate was in short supply, the EPS would be hydrolyzed to sever as carbon and
      energy source.

PMID- 17004053
TI  - Targeted deletion of the uvrBA operon and biological containment in the
      industrially important Bacillus licheniformis.
AB  - From a Bacillus licheniformis wild type as well as a defined asporogenous
      derivative, stable UV hypersensitive mutants were generated by targeted deletion
      of the uvrBA operon, encoding highly conserved key components of the nucleotide
      excision repair. Comparative studies, which included the respective parental
      strains, revealed no negative side effects of the deletion, neither on enzyme
      secretion nor on vegetative propagation. Thus, the uvrBA locus proved to be a
      useful deletion target for achieving biological containment in this industrially
      exploited bacterium. In contrast to recA mutants, which also display UV
      hypersensitivity, further strain development via homologous recombination
      techniques will be still possible in such uvr mutants.

PMID- 17004054
TI  - Outer membrane mutation effects on UDP-glucose permeability and whole-cell
      catalysis rate.
AB  - In whole-cell biocatalysis, cell envelopes represent a formidable barrier for
      substrates to permeate. The present research addresses this critical issue by
      investigating the effects of outer membrane mutation on uridine diphosphate (UDP)
      glucose-utilizing enzymes in whole-cell systems. Owing to the severe limitation
      in substrate permeability, the wild-type Escherichia coli cells only exhibited as
      low as 4% of available enzyme activities. The reduction of the barriers of the
      outer membrane permeability (by mutations in its structure) led to a striking
      acceleration (up to 14-fold) of the reaction rate in cells expressing UDP-glucose
      dehydrogenase. Mutations in the lipopolysaccharide synthesis pathway or Braun's
      lipoprotein are both effective. The acceleration was dependent upon the substrate
      concentrations as well as the enzyme expression level. In addition, the mutation
      has been demonstrated to be much more effective than the freeze-thaw
      permeabilizing method. An application of outer membrane mutants was illustrated
      with the synthesis of a disaccharide (N-acetyllactosamine) from UDP-glucose. Both
      reaction rate and product yield were enhanced significantly (more than twofold)
      in the lipoprotein mutant, demonstrating the importance of the outer membrane
      permeability barrier and the advantages of using outer membrane mutants in
      synthesis. This research and the results outlined in this paper point to a valid
      strategy in addressing permeability issues in whole-cell biocatalysis. It also
      highlights a need for an assessment of substrate permeability in biocatalysis
      research and development.

PMID- 17004055
TI  - Spatial heterogeneity in parasite infections at different spatial scales in an
      intertidal bivalve.
AB  - Spatial heterogeneities in the abundance of free-living organisms as well as in
      infection levels of their parasites are a common phenomenon, but knowledge on
      parasitism in invertebrate intermediate hosts in this respect is scarce. We
      investigated the spatial pattern of four dominant trematode species which utilize
      a common intertidal bivalve, the cockle Cerastoderma edule, as second
      intermediate host in their life cycles. Sampling of cockles from the same cohort
      at 15 sites in the northern Wadden Sea (North Sea) over a distance of 50 km
      revealed a conspicuous spatial heterogeneity in infection levels in all four
      species over the total sample as well as among and within sampling sites. Whereas
      multiple regression analyses indicated the density of first intermediate upstream
      hosts to be the strongest determinant of infection levels in cockles, the
      situation within sites was more complex with no single strong predictor variable.
      However, host size was positively and host density negatively correlated with
      infection levels and there was an indication of differential susceptibility of
      cockle hosts. Small-scale differences in physical properties of the habitat in
      the form of residual water at low tide resulted in increased infection levels of
      cockles which we experimentally transferred into pools. A complex interplay of
      these factors may be responsible for within-site heterogeneities. At larger
      spatial scales, these factors may be overridden by the strong effect of upstream
      hosts. In contrast to first intermediate trematode hosts, there was no indication
      for inter-specific interactions. In other terms, the recruitment of trematodes in
      second intermediate hosts seems to be largely controlled by pre-settlement
      processes both among and within host populations.

PMID- 17004056
TI  - Tropane alkaloids production in transgenic Hyoscyamus niger hairy root cultures
      over-expressing putrescine N-methyltransferase is methyl jasmonate-dependent.
AB  - The cDNA from Nicotiana tabacum encoding Putrescine N-methyltransferase (PMT),
      which catalyzes the first committed step in the biosynthesis of tropane
      alkaloids, has been introduced into the genome of a scopolamine-producing
      Hyoscyamus niger mediated by the disarmed Agrobacterium tumefaciens strain C58C1,
      which also carries Agrobacterium rhizogenes Ri plasmid pRiA4, and expressed under
      the control of the CaMV 35S promoter. Hairy root lines transformed with pmt
      presented fivefold higher PMT activity than the control, and the methylputrescine
      (MPUT) levels of the resulting engineered hairy roots increased four to fivefold
      compared to the control and wild-type roots, but there was no significant
      increase in tropane alkaloids. However, after methyl jasmonate (MeJA) treatment,
      a considerable increase of PMTase and endogenous H6Hase as well as an increase in
      scopolamine content was found either in the transgenic hairy roots or the
      control. The results indicate that hairy root lines over-expressing pmt have a
      high capacity to synthesize MPUT, whereas their ability to convert hyoscyamine
      into scopolamine is very limited. Exposure to MeJA strongly stimulated both
      polyamine and tropane biosynthesis pathways and elicitation led to more or less
      enhanced production simultaneously.

PMID- 17004057
TI  - Fit-for-purpose shellfish reference materials for internal and external quality
      control in the analysis of phycotoxins.
AB  - The need for reference materials for quality control of analysis of foodstuffs
      has been stressed frequently. This has been particularly true in the phycotoxins
      field, where there is a great shortage of both pure calibration standards and
      reference materials. Worldwide there are very few independent bodies that produce
      certified reference materials for phycotoxins, the main producers currently being
      the National Research Council Canada and the Japanese Food Research Laboratory.
      Limited availability of contaminated shellfish and algae, as well as the time and
      knowledge necessary for the production of adequate reference materials,
      continuously lead to limited editions of certified reference materials and even
      more limited production of in-house reference materials. The restricted
      availability of in-house quality control materials promotes the rapid use of the
      limited certified reference materials, which in turn hampers the production of
      the suite of materials required globally for complete protection of public
      health. This paper outlines the various options that analysts can pursue in the
      use of reference materials for internal and external quality control, with a view
      to optimising the efforts of both reference materials users and reference
      materials producers. For this purpose, the logical sequence is reviewed from the
      discovery of a new bioactive compound in shellfish, through initial method
      development up to regulation for food safety purposes including accepted
      reference methods. Subsequently, the requirements for and efforts typically spent
      in the production and characterisation of laboratory reference materials,
      certified reference materials and other test materials used in inter-laboratory
      studies or proficiency testing, in the area of marine biotoxins are evaluated.
      Particular emphasis is put on practical advice for the preparation of in-house
      reference materials. The intricate link between reference material
      characterisation and method performance is outlined to give guidance on the
      appropriate in-house method validation in the rapidly developing field of
      phycotoxins.

PMID- 17004058
TI  - Electrochemical determination of sugars by use of multilayer thin films of
      ferrocene-appended glycogen and concanavalin A.
AB  - Multilayer thin films containing concanavalin A (Con A) and ferrocene-appended
      glycogen (FcGly) were prepared by a layer-by-layer deposition Con A and FcGly by
      biological affinity (lectin-sugar interaction) on a glassy-carbon electrode. The
      electrochemical response of the Con A-FcGly film-coated electrode to sugars was
      investigated. A cyclic voltammogram (CV), typical of redox species confined to
      the surface of the electrode, was obtained. The peak current (resulting from the
      electric charge involved in the redox reaction) in the CV from the electrode
      decreased on addition of sugars in the solution, because the amount of FcGly on
      the electrode surface decreased as a result of disintegration of the Con A-FcGly
      film on addition of sugar. Thus, D-glucose and other sugars at millimole per
      liter levels can be detected by use of Con A-FcGly films-coated electrodes.

PMID- 17004059
TI  - Site-specific acid-base properties of pholcodine and related compounds.
AB  - The acid-base properties of pholcodine, a cough-depressant agent, and related
      compounds including metabolites were studied by 1H NMR-pH titrations, and are
      characterised in terms of macroscopic and microscopic protonation constants. New
      N-methylated derivatives were also synthesized in order to quantitate site- and
      nucleus-specific protonation shifts and to unravel microscopic acid-base
      equilibria. The piperidine nitrogen was found to be 38 and 400 times more basic
      than its morpholine counterpart in pholcodine and norpholcodine, respectively.
      The protonation data show that the molecule of pholcodine bears an average of
      positive charge of 1.07 at physiological pH, preventing it from entering the
      central nervous system, a plausible reason for its lack of analgesic or addictive
      properties. The protonation constants of pholcodine and its derivatives are
      interpreted by comparing with related molecules of pharmaceutical interest. The
      pH-dependent relative concentrations of the variously protonated forms of
      pholcodine and morphine are depicted in distribution diagrams.

PMID- 17004060
TI  - Development of RNR3- and RAD54-GUS reporters for testing genotoxicity in
      Saccharomyces cerevisiae.
AB  - S. cerevisiae RNR3 and RAD54 gene transcription becomes strongly activated upon
      DNA damage. This property was used to construct yeast strains in which DNA damage
      can be monitored by a very sensitive fluorogenic assay in a convenient 96-well
      microtiter plate format. These strains carried stably integrated fusions of RNR3
      or RAD54 promoters to the E. coli beta-glucuronidase GUS gene. GUS activity was
      measured by fluorogenic detection, a method that greatly increases the precision
      and sensitivity of the assay. Detection levels were similar to those of real-time
      quantitative PCR methods and close to the limits of biological response. The two
      reporters differed in terms of fold-induction, activation kinetics, sensitivity
      and specificity upon exposure to a variety of genotoxic compounds. While RNR3-GUS
      showed the fastest response, RAD54-GUS showed the highest sensitivity: similar to
      previous reported sensitivities for bacterial and eukaryotic genotoxic detection
      systems. These reporter strains may complement current genotoxicity tests, but
      they also have the advantages of higher flexibility, requirement for shorter
      incubation times, and the capability of being fully automated. In addition, the
      intrinsic features of the system facilitate its easy improvement by genetic
      manipulating the yeast strain or by introducing mammalian metabolizing enzymes.

PMID- 17004061
TI  - Development of an efficient amine-functionalized glass platform by additional
      silanization treatment with alkylsilane.
AB  - Aminosilane-treated molecular layers on glass surfaces are frequently used as
      functional platforms for biosensor preparation. All the amino groups present on
      the surface are not available in reactive forms, because surface amino groups
      interact with remaining unreacted surface silanol groups. Such nonspecific
      interactions might reduce the efficiency of chemical immobilization of
      biomolecules such as DNA, enzymes, antibodies, etc., in biosensor fabrication. To
      improve immobilization efficiency we have used additional surface silanization
      with alkylsilane (capping) to convert the remaining silanol groups into Si-O-Si
      linkages, thereby liberating the amino groups from nonspecific interaction with
      the silanol groups. We prepared different types of capped amine surface and
      evaluated the effect of capping on immobilization efficiency by investigating the
      fluorescence intensity of Cy3-NHS (N-hydroxysuccinimide) dye that reacted with
      amino groups. The results indicate that most of the capped amine surfaces
      resulted in enhanced efficiency of immobilization of Cy3-NHS compared with the
      untreated control amine surface. We found a trend that trialkoxysilanes had
      greater capping effects on immobilization efficiency than monoalkoxysilanes. It
      was also found that the aliphatic chain of alkylsilane, which does not
      participate in the capping of the silanol, had an important function in enhancing
      immobilization efficiency. These results would be useful for preparation of an
      amine-modified surface platform, with enhanced immobilization efficiency, which
      is essential for developing many kinds of biosensors on a silica matrix.

PMID- 17004063
TI  - Fungal and plant gene expression in arbuscular mycorrhizal symbiosis.
AB  - Arbuscular mycorrhizas (AMs) are a unique example of symbiosis between two
      eukaryotes, soil fungi and plants. This association induces important
      physiological changes in each partner that lead to reciprocal benefits, mainly in
      nutrient supply. The symbiosis results from modifications in plant and fungal
      cell organization caused by specific changes in gene expression. Recently, much
      effort has gone into studying these gene expression patterns to identify a wider
      spectrum of genes involved. We aim in this review to describe AM symbiosis in
      terms of current knowledge on plant and fungal gene expression profiles.

PMID- 17004064
TI  - [Emergency treatment of thoracic trauma].
AB  - Thoracic trauma, most often associated with other serious injuries, is the main
      cause of death in the first 45 years of life. The percentage of chest injuries in
      multiple trauma, mainly from blunt impact, has remained relatively constant at
      80% during the last 30 years. Isolated thoracic injuries comprise only 25% of all
      trauma cases, 90% of chest injuries are due to blunt impact, while penetrating
      injuries make up 5-10%. Since 25% of deaths from trauma are attributable to chest
      injuries, they determine the survival rate in multiple trauma to a significant
      extent. The pattern of chest injuries is variable, frequently in different
      combinations comprising rib cage and diaphragm, lung parenchyma, airway and
      mediastinal organs. This article details the immediate simultaneous diagnostic
      and therapeutic procedures in the prehospital phase, management in the emergency
      room, the relative importance of computed tomography, ultrasound examination and
      endoscopy in the primary diagnostic evaluation and the principles of anaesthetic
      management of thoracic trauma.

PMID- 17004066
TI  - Expression of UNCL during development of periodontal tissue and response of
      periodontal ligament fibroblasts to mechanical stress in vivo and in vitro.
AB  - Mutations in two genes, uncoordinated (unc) and uncoordinated-like (uncl), lead
      to a failure of mechanotransduction in Drosophila. UNCL, the human homolog of unc
      and uncl, is preferentially expressed in periodontal ligament (PDL) fibroblasts
      compared with gingival fibroblasts. However, the precise role of UNCL in the PDL
      remains unclear. The aim of the present study has been to examine whether
      mechanical stimuli modulate the expression of UNCL in the human PDL in vivo and
      in vitro and to examine the roles of UNCL in the development, regeneration, and
      repair of the PDL. We have investigated the expression pattern of UNCL during the
      development of periodontal tissue and the response of PDL fibroblasts to
      mechanical stress in vivo and in vitro. The expression of UNCL mRNA and protein
      increases with PDL fibroblast differentiation from the confluent to multilayer
      stage but slightly decreases on mineralized nodule formation. UNCL has also been
      localized in ameloblasts and adjacent cells, differentiating cementoblasts, and
      osteoblasts of the developing tooth. Strong distinct UNCL expression has further
      been observed in the differentiating cementoblasts of the tooth periodontium at
      the site of tension after orthodontic tooth movement. Application of cyclic
      mechanical stress on PDL fibroblasts increases the expression of UNCL mRNA. These
      results indicate that UNCL plays important roles in the development,
      differentiation, and maintenance of periodontal tissues and also suggest a
      potential role of UNCL in the mechanotransduction of PDL fibroblasts.

PMID- 17004065
TI  - Segmentation of fascias, fat and muscle from magnetic resonance images in humans:
      the DISPIMAG software.
AB  - Segmentation of human limb MR images into muscle, fat and fascias remains a
      cumbersome task. We have developed a new software (DISPIMAG) that allows
      automatic and highly reproducible segmentation of lower-limb MR images. Based on
      a pixel intensity analysis, this software does not need any previous mathematical
      or statistical assumptions. It displays a histogram with two main signals
      corresponding to fat and muscle, and permits an accurate quantification of their
      relative spatial distribution. To allow a systematic discrimination between
      muscle and fat in any subject, fixed boundaries were first determined manually in
      a group of 24 patients. Secondly, an entirely automatic process using these
      boundaries was tested by three operators on four patients and compared to the
      manual approach, showing a high concordance.

PMID- 17004067
TI  - Mechanisms of programmed cell death during oogenesis in Drosophila virilis.
AB  - We describe the features of programmed cell death occurring in the egg chambers
      of Drosophila virilis during mid-oogenesis and late oogenesis. During mid
      oogenesis, the spontaneously degenerating egg chambers exhibit typical
      characteristics of apoptotic cell death. As revealed by propidium iodide,
      rhodamine-conjugated phalloidin staining, and the TUNEL assay, respectively, the
      nurse cells contain condensed chromatin, altered actin cytoskeleton, and
      fragmented DNA. In vitro caspase activity assays and immunostaining procedures
      demonstrate that the atretic egg chambers possess high levels of caspase
      activity. Features of autophagic cell death are also observed during D. virilis
      mid-oogenesis, as shown by monodansylcadaverine staining, together with an
      ultrastructural examination by transmission electron microscopy. During the late
      stages of oogenesis in D. virilis, once again, the two mechanisms, viz., nurse
      cell cluster apoptosis and autophagy, operate together, manifesting features of
      cell death similar to those detailed above. Moreover, an altered form of
      cytochrome c seems to be released from the mitochondria in the nurse cells
      proximal to the oocyte. We propose that apoptosis and autophagy function
      synergistically during oogenesis in D. virilis in order to achieve a more
      efficient elimination of the degenerated nurse cells and abnormal egg chambers.

PMID- 17004068
TI  - Dibutyryl cAMP stimulates the proliferation of SH-SY5Y human neuroblastoma cells
      by up-regulating Skp2 protein.
AB  - PURPOSE: We previously found that the proliferation of SH-SY5Y neuroblastoma
      cells is stimulated when cAMP is up-regulated by stable expression of stimulatory
      G protein. Therefore, this study was performed to investigate the mechanism
      whereby cAMP stimulates the proliferation of SH-SY5Y cells. METHODS: To
      investigate the effect of cAMP on cellular proliferation, SH-SY5Y neuroblastoma
      cells were treated with dibutyryl cAMP (dbcAMP), and then cell growth, thymidine
      incorporation and cell cycle phase distribution were analyzed. The expression and
      the activity of the molecules that regulate cell cycle progression were monitored
      by Western blot, RT-PCR, and kinase activity assay. RESULTS: Treatment with
      dbcAMP produced a biphasic effect on cellular proliferation; especially treatment
      with low concentration of dbcAMP (0.5 mM) showed a higher cellular proliferation
      rate and promoted G1/S transition in cell cycle. The dbcAMP (0.5 mM) treatment
      increased CDK2 activity, and it significantly decreased p27Kip1 expression with a
      decreased half-life of p27Kip1 protein. Moreover, dbcAMP (0.5 mM) increased the
      protein level and the stability of Skp2 with a concomitant decrease in its
      ubiquitination. CONCLUSIONS: cAMP up-regulates Skp2 protein by reducing its
      degradation probably through decreasing the ubiquitination of Skp2, which might
      result in accelerated degradation of p27Kip1, increase in CDK2 activity, and
      stimulation of SH-SY5Y cell proliferation in sequence.

PMID- 17004069
TI  - [Hearing loss in patients with Fabry disease].
AB  - BACKGROUND: Fabry disease is an X-linked lysosomal storage disease involving
      deficient activity of alpha-galactosidase A, which leads initially to pain, and
      later to renal insufficiency, cardiomyopathy and stroke. Until now few details
      are available on hearing impairment in patients with Fabry disease, and
      especially few relating to female patients. PATIENTS AND METHODS: We examined 43
      female and 29 male patients. In this study we looked into the question of whether
      and to what extent patients of both genders are affected by hearing impairment.
      RESULTS: Hearing loss is characteristic being more severe at high frequencies
      frequencies. Overall, 22 female and 15 male patients were found to have suffered
      a hearing loss. Patients with severe symptoms of Fabry disease usually
      demonstrate more prominent hearing losses. CONCLUSIONS: Both men and women with
      Fabry disease are affected by hearing impairment. It seems that the hearing loss
      is less marked in female than in male patients. Children with Fabry disease
      complain of tinnitus more frequently than other children and quite early in the
      course of the disease.

PMID- 17004070
TI  - [The RHINASTHMA-Quality of Life Scale German Adapted Version: validation of a new
      disease specific quality of life scale for patients suffering from allergic
      rhinitis and bronchial hyperreactivity].
AB  - BACKGROUND: In 2003 Baiardini et al. presented the RHINASTHMA questionnaire,
      which measures the impairment of quality of life in patients with rhinitis and
      asthma and takes the "united airway disease" model into its account. The aim of
      our study was to create a valid version of this questionnaire adapted for use
      with German-speaking subjects. METHODS: Datasets recorded for 85 patients were
      analysed for sensitivity, reliability and validity of the new questionnaire. For
      this purpose, as well as the symptom scores, disease-specific and generic quality
      of life questionnaires were also used as a measure of validity. RESULTS: A
      correlation analysis and Cronbach's alpha indicated that the RHINASTHMA scale is
      satisfactory from the aspect of reliability. Good validity was also shown in
      terms of discrimination and agreement for all items and scores. In addition, all
      the observed parameters reacted sensitively to clinical improvements of the
      health status. CONCLUSION: The RHINASTHMA questionnaire makes it possible to
      determine how badly the quality of life is impaired by rhinitis and asthma, based
      on the paradigm of "united airway disease".

PMID- 17004071
TI  - [Experiments on prosody perception with cochlear implants].
AB  - BACKGROUND AND OBJECTIVE: Prosody has a myriad of linguistic functions and
      involves specific aspects of speech, such as stress, intonation and pauses. The
      underlying acoustic quantities (amplitude envelope, pitch frequency, and temporal
      structure) can be processed and transmitted by cochlear implants (CI) only to a
      limited extent. At present, no adequate tests are available in the German
      speaking world for evaluation of the perception of prosodic elements. Different
      experiments have been conducted to address several prosodic cues, and the results
      are to be used as a basis for appropriate tests. METHODS: Various prosodic
      materials were used for the experiments. Discrimination was measured for minimal
      pairs differing in frequency and/or duration, accents in words and phrases,
      questions versus statements and phrasing. Measurements were performed in ten
      normal-hearing subjects and five with cochlear implants. RESULTS AND CONCLUSIONS:
      In all test modules, the subjects with normal hearing proved to have high
      discrimination rates of 96-100%. The test of word stresses was problematic
      because the results were influenced by different confounders. The other
      measurements did prove to be basically suitable for use in the subjects with
      implants. Early results revealed that the subjects with CI had few problems with
      prosodic cues based on the temporal structure, the outcome being similar to that
      of the subjects with normal hearing in these tests. In contrast, the performance
      of subjects with CI in perceiving prosodic cues based on amplitude variations
      and, especially, on alterations in pitch frequency was worse, even though some of
      them achieved very good results in these tests too. These preliminary tests can
      form the basis for development of a German-language prosody test battery with a
      limited number of subtests addressing different prosodic cues.

PMID- 17004072
TI  - Chromosome segregation in fission yeast with mutations in the tubulin folding
      cofactor D.
AB  - Faithful chromosome segregation requires the combined activities of the
      microtubule-based mitotic spindle and the multiple proteins that form mitotic
      kinetochores. Here, we show that the fission yeast mitotic mutant, tsm1-512, is
      an allele of the tubulin folding chaperone, cofactor D. Chromosome segregation in
      this and in an additional cofactor D mutant depends on growth conditions that are
      monitored specifically by the mitotic checkpoint proteins Mad1, 2, 3 and Bub3.
      The temperature-sensitive mutants we have used disrupt the function of cofactor D
      to different extents, but both strains form a mitotic spindle in which the poles
      separate in anaphase. However, chromosome segregation is often unequal,
      apparently due to a defect in kinetochore-microtubule interactions. Mutations in
      cofactor D render cells particularly sensitive to the expression levels of a CENP
      B-like protein, Abp1p, which works as an allele-specific, high-copy suppressor of
      cofactor D. This and other genetic interactions between cofactor D mutants and
      specific kinetochore and spindle components suggest their critical role in
      establishing the normal kinetochore-microtubule interface.

PMID- 17004073
TI  - Oxidation-state-dependent reactions of cytochrome c with the trioxidocarbonate(*1
      ) radical: a pulse radiolysis study.
AB  - The reaction of the trioxidocarbonate(*1-) radical (CO (3) (*-) , "carbonate
      radical anion") with cytochrome c was studied by pulse radiolysis at alkaline pH
      and room temperature. With iron(III) cytochrome c, CO (3) (*-) reacts with the
      protein moiety with rate constants of (5.1 +/- 0.6) x 10(7) M(-1) s(-1) (pH 8.4,
      I approximately 0.27 M) and (1.0 +/- 0.2) x 10(8) M(-1) s(-1) (pH 10, I = 0.5 M).
      The absorption spectrum of the haem moiety was not changed, thus, amino acid
      radicals produced on the protein do not reduce the haem. The pH-dependent
      difference in rate constants may be attributed to differences in ionization
      states of amino acids and to the change in the conformation of the protein. With
      iron(II) cytochrome c, CO (3) (*-) oxidizes the haem quantitatively, presumably
      via electrostatic guidance of the radical to the solvent-accessible haem edge,
      with a different pH dependence: at pH 8.4, the rate constant is (1.1 +/- 0.1) x
      10(9) M(-1) s(-1) and, at pH 10, (7.6 +/- 0.6) x 10(8) M(-1) s(-1). We propose
      that CO (3) (*-) oxidizes the iron center directly, and that the lower rate
      observed at pH 10 is due to the different charge distribution of iron(II)
      cytochrome c.

PMID- 17004074
TI  - Monostotic fibrous dysplasia of the spine: report of a case involving a cervical
      vertebra.
AB  - Monostotic fibrous dysplasia of the spine is a rare entity. Only 26 cases, of
      which 11 were located in the cervical spine, are to be found in the literature.
      We report a 56-year-old male patient with cervicobrachialgia of half year's
      duration. Radiographs showed a diffuse destruction of the vertebral body and the
      spinous process of C4. A biopsy of the spinous process confirmed
      histopathologically a fibrous dysplasia. Due to minor symptoms, no surgical
      treatment was performed or is planned unless in case of increasing pain, an acute
      instability or neurological symptoms.

PMID- 17004075
TI  - Fixation of nondisplaced scaphoid fractures: making treatment cost effective.
      Prospective controlled trial.
AB  - INTRODUCTION: Nondisplaced scaphoid waist fractures treated with prolonged
      plaster immobilisation often lead in transient joint stiffness and to a delay in
      return to sport and work activity. The long time off work increases the work off
      compensation costs. Internal fixation of scaphoid fractures has resulted in a
      shorter time to union and to return to work and sports. This prospective study
      compares cast immobilisation with screw fixation and the direct cost with
      indirect cost of conservative and minimally invasive treatment of undisplaced
      scaphoid fractures. MATERIALS AND METHODS: Forty-seven patients with an acute
      nondisplaced waist fracture of the scaphoid were allocated into either cast
      immobilisation or internal screw fixation for this study. Cost data concerning
      the groups of nonoperated and operated patients were analysed. Range of wrist
      motion, grip strength, DASH-score, time to fracture union, return to work time
      and the needed physiotherapy at the final follow-up at 6 months were evaluated.
      RESULTS: Twenty-one patients were included in the group of screw fixation and 23
      patients were included in the group of cast immobilisation. At final follow-up
      there was no significant difference in the range of motion of the wrist or in
      grip strength. The operatively treated group had a better mean DASH-score than
      the conservative group. Fracture union was seen in the screw fixation group at a
      mean of 43 days and in the cast immobilisation group at a mean of 74 days (P <
      0.5). The average time of return to work was 8 days for patients who had an
      internal screw fixation, while those treated with a cast returned to work at a
      mean of 55 days (P < 0.5). In total the internal fixation of undisplaced scaphoid
      fractures is less expensive than conservative treatment. CONCLUSION: Internal
      screw fixation of nondisplaced scaphoid fractures had a shorter time to bony
      union and the patients returned earlier to work compared with cast
      immobilisation. Although it is assumed that operative treatment is more
      expensive, in this study the cost was not found to be higher.

PMID- 17004076
TI  - Long-term results of pilon fractures.
AB  - INTRODUCTION: The long-term results of pilon fractures are rarely documented. The
      present study evaluated the long-term results related to each fracture pattern of
      a pilon fracture treated with open reduction and plating. PATIENTS: One hundred
      and twenty-eight pilon fractures with a mean 10-year follow-up were divided into
      three groups, based on the Ruedi-Allgower classification. Group A was composed of
      39 patients with Ruedi-Allgower type I fractures; group B comprised 62 patients
      with type II fractures; and group C included 27 patients with type III fractures.
      The radiographs were reviewed for adequacy of fracture reduction and
      posttraumatic arthrosis. At the end of follow-up, the clinical results were
      evaluated using a rating scale. RESULTS: Group C had significantly lower
      excellent and good reduction rates than group A or B (P < 0.05). Groups B and C
      had progressively increased ankle arthrosis with time (P = 0.043, P = 0.049,
      respectively). Group C had more unsatisfactory clinical outcomes than group A or
      B (P < 0.05). Operative concurrent fixation of the fractured fibula resulted in a
      better outcome than non-operative treatment (P < 0.05). Open fractures had
      significantly lower satisfactory outcomes than closed fractures (60.5% versus
      78.9%, P < 0.05). CONCLUSIONS: Open reduction with plating was a reasonably
      effective procedure for the treatment of Ruedi type I pilon fractures. The long
      term outcome of pilon fractures was affected by fracture patterns, fibular length
      restoration, quality of reduction, and severity of soft tissue injury.
      Posttraumatic arthrosis affecting the ankle after a severe pilon fracture (Ruedi
      type II or III) was a progressive disease, and required long-term follow-up.

PMID- 17004078
TI  - Retraction. Shed blood transfusion and its effect on postoperative fever: a
      comparative study.

PMID- 17004077
TI  - Arthroscopic-assisted correction of claw toe or overriding toe deformity: plantar
      plate tenodesis.
AB  - Hyperextension of the metatarsophalangeal joint is the key component of claw toe
      deformity. We describe an arthroscopic technique to stabilize the plantar plate
      and reduce the metatarsophalangeal joint. Under arthroscopic guide, the dorsal
      capsule is released. The plantar plate is anchored and sutured to the extensor
      digiturum longus tendon. In case of overriding toe deformity, the medial capsule
      is also reduced and lateral capsule is plicated under arthroscopic guide.

PMID- 17004079
TI  - Optimizing US examination to detect the normal and abnormal appendix in children.
AB  - BACKGROUND: US detection of a normal appendix can safely rule out appendicitis.
      However, there is a wide range of accuracy in detection of a normal appendix.
      OBJECTIVE: To optimize US examination to detect the normal and the abnormal
      appendix according to the potential positions of the appendix. MATERIALS AND
      METHODS: This prospective study included 107 children who underwent gray-scale US
      scanning. Noncompressive and compressive graded sonography was performed to
      detect normal and abnormal appendices according to their potential positions. The
      maximum transverse diameter of the appendices was measured. RESULTS: Of the 107
      children examined, 56 had a histologic diagnosis of acute appendicitis.
      Sonography had a sensitivity of 100% and specificity of 98% for the diagnosis of
      appendicitis. A normal appendix was visualized in 44 (86.2%) of the 51 patients
      without acute appendicitis, and of these 44, 43 were true-negative and 1 was
      false-positive. Normal and abnormal appendices, respectively, were positioned as
      follows: 54.4% and 39.3% were mid-pelvic; 27.2% and 28.6% were retrocecal; 11.4%
      and 17.8% were deep pelvic; and 6.8% and 14.3% were abdominal. CONCLUSION: US
      scanning according to the potential positions of the appendix was useful in the
      detection of normal appendices in children suspected of having appendicitis.

PMID- 17004080
TI  - Spontaneous delivery is related to barometric pressure.
AB  - BACKGROUND: Many studies have shown that changes in the weather affect health. In
      the field of obstetrics and gynecology, several events have been empirically
      shown to be related to the weather. Labor pain is controlled by the autonomic
      nervous system and various hormones, and is expected to be influenced by the
      weather and environmental changes. Several studies have been conducted on the
      relationship between delivery and barometric pressure, which shows constant
      changes with changes in weather, but there is no generally accepted view on this.
      METHODS: We conducted a retrospective study in our patients who had a spontaneous
      cephalic delivery in this hospital between January 1997 and December 2003, in
      order to determine whether low barometric pressure induces labor pains, premature
      rupture of the membranes, and delivery, and whether changes in barometric
      pressure affect delivery. RESULTS: There was a significant increase in the number
      of deliveries and rupture of the membranes at low barometric pressure (P < 0.01),
      although there was no significant correlation between onset of labor and
      barometric pressure. This tendency was noted in both women with spontaneous
      rupture of the fetal membranes and those with premature rupture of the membranes
      (P < 0.01). On days with a larger change in barometric pressure, regardless of
      whether it was increasing or decreasing, the number of deliveries increased and
      the relationship was statistically significant (P < 0.01). CONCLUSIONS: A causal
      relationship was noted between the number of rupture of the fetal membranes,
      delivery and barometric pressure, suggesting that low barometric pressure induces
      rupture of the fetal membranes and delivery.

PMID- 17004081
TI  - [Prospective study of the direct and indirect costs of idiopathic Parkinson's
      disease].
AB  - Idiopathic Parkinson's disease is a chronic progressive neurodegenerative
      disorder that remains refractory to curative treatment. Most patients are
      afflicted for many years, and the disease frequently results in severe physical
      handicap. Statements on the considerable cost of treatment are largely based on
      estimates and retrospective studies. To obtain more substantial data, we
      conducted a 3-year study of the economic aspects. Direct and indirect costs
      incurred by 117 patients (78 male, mean age 67.5 years) at the Deutsche Klinik
      fur Diagnostik in Wiesbaden, Germany, were prospectively followed. The average
      cost per patient and month ran to <euro> 1007.55. Of that, direct costs amounted
      to <euro> 603.33 (55.9%), with drugs taking up the major share at <euro> 480.23.
      Indirect costs were <euro> 404.22 per patient and month, with 76% thereof related
      to nursing care and the incapacity to earn a living. Cost increased in proportion
      to Hoehn and Yahr stage, declining again with stages 4 and 5. The data we
      gathered confirm that Parkinsonism is responsible for sizeable expenses for not
      only the treating unit but the national economy as a whole.

PMID- 17004082
TI  - Use of the transposable element Ac/Ds in conjunction with Spm/dSpm for gene
      tagging allows extensive genome coverage with a limited number of starter lines:
      functional analysis of a four-element system in Arabidopsis thaliana.
AB  - We have developed a novel four-element based gene tagging system in Arabidopsis
      to minimize the number of starter lines required to generate genome-wide
      insertions for saturation mutagenesis. In this system, the non-autonomous
      cassette, Ds(dSpm), comprises of both Ds and dSpm elements cloned one within the
      other along with appropriate selection markers to allow efficient monitoring of
      excision and re-integration of the transposons. Trans-activation of the outer
      borders (Ds) and selection against the negative selection marker (iaaH) linked to
      the cassette ensures unlinked spread of the Ds(dSpm) cassette from the initial
      site of integration of the T-DNA. This creates several launch pads within the
      genome from where the internal element (dSpm) can be subsequently mobilized to
      generate secondary insertions. In this study, starting from a single T-DNA
      integration we could spread the Ds(dSpm) cassette to 11 different locations over
      all the five chromosomes of Arabidopsis. The frequency of unlinked Ds
      transpositions in the F2 generation varied between 0.05 and 3.35%. Three of these
      lines were then deployed to trans-activate the internal dSpm element which led to
      the selection of 29 dSpm insertions. The study conclusively shows the feasibility
      of deploying Ds and the dSpm elements in a single construct for insertional
      mutagenesis.

PMID- 17004083
TI  - Prevention and management of intraprocedural rupture of intracranial aneurysm
      with detachable coils during embolization.
AB  - INTRODUCTION: Intracranial aneurysm rupture during embolization with detachable
      coils is reportedly among the gravest of intraprocedural complications. We
      present here our experiences with this outcome, and a potential intervention for
      managing this life-threatening complication. METHODS: From April 1998 to March
      2005, 284 patients with cerebral aneurysms were treated with detachable coils.
      Intraprocedural aneurysm rupture occurred in ten patients with a history of a
      previously ruptured aneurysm. In the event of intraprocedural hemorrhage, we
      routinely performed heparin reversal with protamine sulfate. RESULTS: Of the 221
      patients with a previously ruptured aneurysm, intraprocedural aneurysm rupture
      occurred in 10 (4.5%). These ruptures were caused by a micro-guide wire in one
      patient, a microcatheter in one, over-packing in two and a coil perforation in
      three. In the remaining three patients the ruptures were caused by both the
      microcatheter and the coils. Three patients died because of aneurysm re-rupture,
      yielding a mortality rate of 30%. One patient presented with a slight disability
      in the left leg and no neurological deficits were observed in the remaining six
      patients. CONCLUSION: Intraprocedural aneurysm rupture during embolization is a
      rare, but unavoidable and life-threatening event. Proper measures should be taken
      to reduce and improve the outcome of this tragic occurrence. The majority of
      patients with an intraprocedural ruptured aneurysm can survive without severe
      sequelae if managed appropriately.

PMID- 17004084
TI  - Initial primary endovascular treatment in the management of ruptured intracranial
      aneurysms: a prospective consecutive series.
AB  - INTRODUCTION: From January 1998 to December 2002, endovascular treatment (EVT)
      was used as first intention in all patients with ruptured aneurysms. The
      objective of this study was to analyze the results of this therapeutic strategy.
      METHODS: Among 401 patients admitted with a subarachnoid hemorrhage (SAH), 73
      (18%) had a nonaneurysmal perimesencephalic SAH, 28 were not explored by
      angiography due to very poor clinical status, and 28 with aneurysmal SAH were not
      treated due to poor clinical status. Thus, of the 300 patients with a proven
      aneurysmal SAH, 272 (83%) were treated. EVT was attempted in 230 patients and was
      successful in 222 (82%), and clipping was performed in 50 (18%). RESULTS:
      Finally, EVT was successful in 234 aneurysms (96.7%) in 222 patients out of 242
      aneurysms in 230 patients (some of the patients were treated for more than one
      aneurysm in the same procedure). EVT-related morbidity occurred in ten patients
      (4.5%) and mortality in eight (3.6%). Rate of dependency or death (modified
      Rankin scale 3-5) was 24.5% at 26 months. Initially, complete aneurysm occlusion
      was obtained in 81%, a dog ear in 3.4%, a neck remnant in 8% and incomplete
      occlusion in 8.1% of the patients. At follow-up (mean 26 months), the occlusion
      rate remained stable at 75%. CONCLUSION: This consecutive prospective series
      shows that EVT can be performed routinely as first-intention treatment in most
      aneurysmal SAH. Using this therapeutic strategy, EVT was performed in 82% of
      patients with long-term clinical results similar to those of the ISAT study.

PMID- 17004085
TI  - Donepezil primarily attenuates scopolamine-induced deficits in psychomotor
      function, with moderate effects on simple conditioning and attention, and small
      effects on working memory and spatial mapping.
AB  - RATIONALE: Alzheimer's dementia (AD) patients have profound deficits in cognitive
      and social functions, mediated in part by a decline in cholinergic function.
      Acetylcholinesterase inhibitors (AChEI) are the most commonly prescribed
      treatment for the cognitive deficits in AD patients, but their therapeutic
      effects are small, and it is still not clear if they primarily affect attention,
      memory, or some other cognitive/behavioral functions. OBJECTIVES: The objective
      of the present experiments was to explore the effects of donepezil (Aricepttrade
      mark), an AChEI, on behavioral deficits related exclusively to cholinergic
      dysfunction. MATERIALS AND METHODS: The effects of donepezil were assessed in
      Sprague-Dawley rats with scopolamine-induced deficits in a battery of
      cognitive/behavioral tests. RESULTS: Scopolamine produced deficits in contextual
      and cued fear conditioning, the 5-choice serial reaction time test, delayed
      nonmatching to position, the radial arm maze, and the Morris water maze. Analyses
      of the pattern and size of the effects revealed that donepezil produced very
      large effects on scopolamine-induced deficits in psychomotor function
      (approximately 20-50% of the variance), moderate-sized effects on scopolamine
      induced deficits in simple conditioning and attention (approximately 3-10% of the
      variance), but only small effects on scopolamine-induced deficits in higher
      cognitive functions of working memory and spatial mapping (approximately 1% of
      the variance). CONCLUSIONS: These results are consistent with the limited
      efficacy of donepezil on higher cognitive function in AD patients, and suggest
      that preclinical behavioral models could be used not only to determine if novel
      treatments have some therapeutic potential, but also to predict more precisely
      what the pattern and size of the effects might be.

PMID- 17004086
TI  - Substance and tongue-region specific loss in basic taste-quality identification
      in elderly adults.
AB  - Physiological anorexia, decreased dietary variation, and weight loss associated
      with poor health are common conditions in the elderly population, with changes in
      chemosensory perception as important contributing causes. The present study of
      age-related taste loss aimed to investigate the question whether this loss is
      generalised and unspecific, or whether it exhibits differences in relation to
      certain tastants and/or differences in the topographical distribution of age
      related loss. Impregnated "taste strips" with four concentrations of each of the
      tastants sucrose, NaCl, quinine-hydrochloride, and citric acid were applied on
      the tip, midlateral and posteromedial tongue regions to be identified as either
      sweet, salty, bitter, or sour by 30 young and 26 elderly adults. The results
      showed more pronounced age-related loss in identification for citric acid and
      quinine-hydrochloride than for sucrose and NaCl at both the tip and midlateral
      regions, but not at the posteromedial region where both age groups performed
      close to chance level. These findings may have implications for food preferences,
      and thus, the diets of elderly people.

PMID- 17004087
TI  - Indication for the need of flexible and frequency specific mapping functions in
      cochlear implant speech processors.
AB  - Categorical loudness scaling of electric and acoustic stimuli was performed in
      cochlear implant (CI) recipients equipped with Nucleus systems in order to
      achieve a normal loudness perception in the whole dynamic range of acoustic
      input. For each electrode, the lower and upper limits of electric stimulus were
      defined by the values corresponding to "very soft" and "too loud". Within this
      dynamic range, the stimulus strength intervals associated to the verbal
      categories "soft", "medium", "loud" and "very loud" were determined. The same
      loudness categories were used for the scaling of acoustic stimuli. From both
      scaling experiments, the transduction of the CI system can be assessed and the
      parameters of the individual mapping function yielding a normal loudness growth
      can be derived. Deviations from optimum mapping can be corrected at least
      partially by manipulating the parameters of the mapping function. In many cases,
      however, one mapping function is not sufficient for all channels. The results
      argue in favour of the development of flexible and channel-specific mapping
      function parameters in future CI systems.

PMID- 17004088
TI  - Intratympanic membrane cholesteatoma: a rare incidental finding.
AB  - Intratympanic membrane cholesteatoma, occurring in the absence of trauma or
      surgery to the ear, is rare with less than 20 cases reported in the literature.
      We report a rare incidental finding of intratympanic membrane cholesteatoma in a
      12-month-old girl and review the literature.

PMID- 17004089
TI  - Prevalence and localization of nodal metastases in squamous cell carcinoma of the
      oral cavity: role and extension of neck dissection.
AB  - Lymph node (LN) metastases represent the most important negative prognostic
      factor in squamous cell carcinoma (SCC) of the oral cavity, even though
      controversies still exist regarding their management. The aim of this study was
      to retrospectively analyze our experience in surgical management of SCC of the
      oral cavity with particular focus on the prevalence and localization of lymph
      nodal metastases and recurrences. The clinical records of 89 consecutive patients
      treated from 1983 to 2002 by concomitant surgery on both the T and N sites,
      excluding those undergoing salvage surgery, were reviewed. A total of 119 neck
      dissections (ND) were performed. Survival outcomes were calculated by the Kaplan
      Meier method, while univariate comparisons by the log-rank and non-parametric
      tests were performed between different groups of patients. Five-year overall and
      determinate survivals were 50 and 57%, respectively. LN metastases were observed
      in 52% (56% of these showing extracapsular spread) and their presence strongly
      correlated with determinate survival (p < 0.0001). The prevalence of clinical and
      occult nodal disease was not related to the pT status. Neck levels II (59%) and I
      (56%) were most frequently involved. Metastases to level IV accounted for 15% of
      positive LN, even though 28% of them turned out to be skip metastases. Five neck
      recurrences were observed, only one of which was salvaged by surgery. The high
      prevalence of clinical and occult LN metastases in this setting suggests that ND
      should be performed on a nearly routine basis, even for lesions with a low-T
      category and a cN0 neck. Moreover, ND should always encompass level IV due to the
      possibility of skip metastases, particularly in tumors involving the oral tongue.
      In patients with a cN+ neck, levels from I to V should be addressed, particularly
      in the presence of metastases at levels III and IV.

PMID- 17004090
TI  - Social support and survival in patients with acute myeloid leukaemia.
AB  - GOAL OF WORK: The purpose of the study was to assess the effect of the reported
      availability of social support on the 2-year survival of patients with acute
      myelogenous leukaemia (AML). MATERIALS AND METHODS: Fifty patients with newly
      diagnosed AML were asked to rate the level of available social support after
      diagnosis was made, but before the start of chemotherapy. Social support was
      assessed with the F-SozU, and information about confounding variables (age,
      functional status, intensity of chemotherapy, cytogenetic risk group) was
      collected. Univariate and multivariate Cox regression analyses were used to
      analyze predictors of 2-year survival. MAIN RESULTS: Higher levels of available
      social support predicted better survival, even after controlling for age,
      functional status, dosage of chemotherapy, and cytogenetic risk group. Within
      social support, the availability of instrumental support showed more consistent
      associations with 2-year survival than the availability of emotional support.
      CONCLUSIONS: For patients with AML, the availability of social support is
      relevant for decreased mortality, after accounting for age, functional
      impairment, dosage of chemotherapy and cytogenetic risk group.

PMID- 17004091
TI  - [Association of a positive family history with histopathology and clinical course
      in early-onset prostate cancer].
AB  - BACKGROUND: In a large number of studies a positive family history is documented
      as one of the main risk factors for the development of prostate cancer. In a US
      population an association between early-onset prostate cancer among familial
      patients and a more differentiated tumour was shown. The aim of this study was to
      compare clinical parameters between sporadic and familial or hereditary patients
      with an age at diagnosis < or =55 years. MATERIAL AND METHODS: The clinical data
      of prostate cancer patients with an age at diagnosis < or =55 years and who were
      recruited between July 1999 and the end of June 2004 to the database "familial
      prostate cancer in Germany" were analysed. The following data were documented for
      all patients: PSA at diagnosis, histopathological stage, grading, Gleason score
      and progression-free survival. RESULTS: The clinical data of 685 patients could
      be completed: 222 (32.4%) had one first-degree relative with prostate cancer, 48
      of whom (7.0%) were hereditary; 463 (67.6%) were sporadic. The median age at
      diagnosis in the hereditary patients was 51.6 (41-55) years, in the familial
      patients 51.1 (35-55) years and in the sporadic patients 52.0 (38-55) years. The
      median follow-up was 24 months in hereditary, 36 months in familial and 35 months
      in sporadic patients. An initial curative therapy with radical prostatectomy or
      radiotherapy/brachytherapy was planned in 657/685 (95.9%) of the patients. There
      were no clear differences regarding PSA at diagnosis, the postoperative
      parameters (organ-confined disease, lymph node involvement, Gleason score,
      grading) and the progression-free survival in sporadic and familial or hereditary
      patients. CONCLUSIONS: Patients with an age at diagnosis < or =55 years have a
      positive family history more often than all prostate cancer patients in Germany.
      No association could be shown between pathohistological stage or clinical course
      and a positive family history in patients with an age at diagnosis < or =55
      years.

PMID- 17004092
TI  - Telmisartan inhibits AGE-induced C-reactive protein production through
      downregulation of the receptor for AGE via peroxisome proliferator-activated
      receptor-gamma activation.
AB  - AIMS/HYPOTHESIS: C-reactive protein (CRP), an acute-phase reactant produced
      mainly by the liver, is elevated in diabetes, thus contributing to the
      development and progression of atherosclerosis. However, the molecular mechanism
      underlying the elevation of CRP in diabetes is not fully understood. Since a
      crosstalk between AGE and angiotensin II (Ang II) has been proposed in the
      pathogenesis of accelerated atherosclerosis in diabetes, we examined here whether
      and how telmisartan, a unique Ang II type 1 receptor blocker (ARB) with
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-modulating
      activity, could inhibit AGE-induced CRP expression in a human hepatoma cell line,
      Hep3B cells. METHODS: Protein levels of the receptor for AGE (RAGE) were analysed
      by western blots. Gene expression was analysed by quantitative real-time RT-PCR.
      CRP released into the medium was measured with ELISA. Intracellular formation of
      reactive oxygen species (ROS) was measured using the fluorescent probe CM
      H(2)DCFDA. RESULTS: Telmisartan, but not candesartan, another ARB, downregulated
      RAGE mRNA levels in a dose-dependent manner. Telmisartan decreased basal as well
      as AGE-induced RAGE protein expression in Hep3B cells. Furthermore, telmisartan
      dose-dependently inhibited AGE-induced ROS generation and subsequent CRP gene and
      protein induction in Hep3B cells. GW9662, an inhibitor of PPAR-gamma, blocked the
      inhibitory effects of telmisartan on RAGE expression and its downstream
      signalling in Hep3B cells. CONCLUSIONS/INTERPRETATION: Our present study
      indicates a unique beneficial aspect of telmisartan: it may work as an anti
      inflammatory agent against AGE by suppressing RAGE expression via PPAR-gamma
      activation in the liver and may play a protective role in vascular injury in
      diabetes.

PMID- 17004093
TI  - Regeneration of the esophagus using gastric acellular matrix: an experimental
      study in a rat model.
AB  - Recently, tissue engineering of the autologous esophagus has been thought to
      provide a promising strategy for esophageal substitution. In this study, gastric
      acellular matrix (GAM) was used as a scaffold for regeneration of the esophagus
      in a rat model. Usage of GAM has an advantage that naturally derived
      extracellular matrix autograft can be prepared less invasively in a clinical
      setting. Twenty-seven F344 female rats were used as recipients. Patch defects
      created in the abdominal esophagus were replaced by GAM patch grafts. The rats
      were sacrificed 1 week to 18 months after implantation. The specimen was examined
      macroscopically as well as microscopically. 5'-Bromo-2'-deoxyuridine (BrdU)
      proliferation assay was performed in six rats that were sacrificed 1, 2, and 4
      weeks after implantation. Twenty-four rats survived without complications. The
      graft site did not show esophageal stenosis or dilatation in any rat. Keratinized
      stratified squamous esophageal mucosa was regenerated in the entire graft 2 weeks
      after implantation. Regeneration of the muscle layer or lamina muscularis mucosae
      in the graft site was not observed even 18 months after implantation. Marked
      incorporation of BrdU was observed only in the mucosal layer but not in the
      muscle layer. GAM patch graft provided satisfactory mucosal regeneration of the
      esophagus without stenosis or dilatation, although muscle regeneration was still
      a future challenge.

PMID- 17004094
TI  - A review of vascular surgery in the pediatric population.

PMID- 17004095
TI  - Assessment of non-reperfused and reperfused myocardial infarction using
      diffusible or deposited radiolabelled perfusion imaging agents.
AB  - PURPOSE: Incomplete microvascular reperfusion is often observed in patients
      undergoing thrombolytic therapy or angioplasty for acute myocardial infarction
      and has important prognostic implications. We compared the myocardial uptake of
      diffusible ((201)Tl) and deposited ((99m)TcN-NOET) perfusion imaging agents in
      the setting of experimental infarction. METHODS: Rats were subjected to permanent
      coronary occlusion (OCC, n=10) or to 45-min occlusion and reperfusion (REP,
      n=17). Seven days later, the tracers were co-injected and the animals were
      euthanised 15 min (all ten rats in the OCC group and 12 rats in the REP group) or
      120 min (five rats from the REP group, euthanised at this time point to evaluate
      any redistribution of the tracers: REP-RED group) afterwards. Infarct size
      determination and (99m)TcN-NOET/(201)Tl ex vivo imaging were performed. Regional
      flow and tissue oedema were quantified using radioactive microspheres and (99m)Tc
      DTPA, respectively. RESULTS: (99m)TcN-NOET and (201)Tl defect magnitudes were
      similar in OCC animals (0.11+/-0.01 vs 0.13+/-0.01). In REP animals, (201)Tl
      defect magnitude (0.25+/-0.02) was significantly lower than the magnitude of
      (99m)TcN-NOET and flow defects (0.14+/-0.03 and 0.17+/-0.01, respectively;
      p<0.05), despite the lack of (201)Tl redistribution (REP-RED animals). (99m)Tc
      DTPA indicated the presence of oedema in the reperfused area. Blood distribution
      studies showed that, unlike (99m)TcN-NOET, (201)Tl plasma activity was mostly
      unbound to plasma proteins. CONCLUSION: (99m)TcN-NOET and (201)Tl delineated the
      non-viable area in chronic non-reperfused and reperfused myocardial infarction.
      The significantly decreased (201)Tl defect in reperfused infarction was likely
      due to partial diffusion of the tracer from the plasma into the oedema present in
      the infarcted area. Deposited perfusion tracers might be better suited than
      diffusible agents for the assessment of regional flow following reperfusion of
      myocardial infarction.

PMID- 17004096
TI  - Cerebral malaria in spite of peripheral parasite clearance in a patient treated
      with atovaquone/proguanil.
AB  - Cerebral malaria, the most frequent complication of falciparum malaria, is
      usually predicted by an increased count of asexual parasites in peripheral blood.
      We report a case of a female returnee from Ghana who developed cerebral malaria
      in spite of parasite clearance in peripheral blood after therapy with
      atovaquone/proguanil.

PMID- 17004097
TI  - Comparison of 18S ribosomal RNA gene sequences of Eurytrema coelmaticum and
      Eurytrema pancreaticum.
AB  - The partial 18S rRNA sequences of E. coelmaticum and E. pancreaticum were
      amplified using conserved primers and an evolutionary tree was constructed using
      Neighbor-Joining. The percent identity of Eurytrema species with other
      Dicrocoeliidae varied from 97.5 to 98.2, while the percent identity between the
      two Eurytrema species was up to 99.3. The tree showed that E. coelmaticum and E.
      pancreaticum were not situated in the same position, and they formed one cluster
      with L. collurioni. These results support a confirmation with molecular data that
      E. coelomaticum and E. pancreaticum are different species which apparently were
      not seriously questioned in the past.

PMID- 17004098
TI  - Fluorescent in situ hybridization as a tool to retrospectively identify
      Cryptosporidium parvum and Giardia lamblia in samples from terrestrial mammalian
      wildlife.
AB  - Fecal samples of five terrestrial mammalian wildlife species stored at 4 degrees
      C or at -20 degrees C for up to 36 months have been tested for human zoonotic
      enteric parasites (i.e., Cryptosporidium parvum and Giardia lamblia) using
      combined fluorescent in situ hybridization (FISH) and direct fluorescent antibody
      techniques. The prevalence of C. parvum and G. lamblia varied from 20 to 63%
      (mean, 45.8%) and from 13 to 100% (mean, 53.2%), respectively. The prevalence of
      C. parvum and G. lamblia infections was higher in small rodents (mean, 68.5%)
      than in other wildlife (mean, 21%). Overall, 31.1% of animals were coinfected,
      and coinfections were more prevalent in small rodents (mean, 52%) than in other
      wildlife species (mean, 13.2%). The present study has shown that the FISH assay
      can be retrospectively applied to fecal samples for the identification of C.
      parvum oocysts, but is less suitable for the identification of G. lamblia cysts
      in such samples. Terrestrial mammalian wildlife, particularly small rodents, can
      contribute to watershed contamination with C. parvum oocysts and G. lamblia
      cysts. To control contamination, the management of pristine watersheds used for
      drinking water purposes should incorporate control measures for terrestrial
      wildlife, especially field rodents residing within such watersheds.

PMID- 17004099
TI  - Molecular identification of Trichuris vulpis and Trichuris suis isolated from
      different hosts.
AB  - Trichuris suis was isolated from the cecum of two different hosts (Sus scrofa
      domestica -- swine and Sus scrofa scrofa -- wild boar) and Trichuris vulpis from
      dogs in Sevilla, Spain. Genomic DNA was isolated and internal transcribed spacers
      (ITS)1-5.8S-ITS2 segment from the ribosomal DNA (rDNA) was amplified and
      sequenced using polymerase chain reaction techniques. The sequence of T. suis
      from both hosts was 1,396 bp in length while that of T. vulpis was 1,044 bp. ITS1
      of both populations isolated of T. suis was 661 nucleotides in length, while the
      ITS2 was 534 nucleotides in length. Furthermore, the ITS1 of T. vulpis was 410
      nucleotides in length, while the ITS2 was 433 nucleotides in length. One hundred
      fifty-four nucleotides were observed along the 5.8S gene of T. suis and T.
      vulpis. Intraindividual and intraspecific variations were detected in the rDNA of
      both species. The presence of microsatellites was observed in all the individuals
      assayed. Sequence analysis of the ITSs and the 5.8S gene has demonstrated no
      sequence differences between T. suis isolated from both hosts (S. scrofa
      domestica -- swine and S. scrofa scrofa -- wild boar). Nevertheless, clear
      differences were detected between the ITS1 and ITS2 of T. suis and T. vulpis.
      Furthermore, a comparative molecular analysis between both species and the
      previously published ITS1-5.8S-ITS2 sequence data of Trichuris ovis, Trichuris
      leporis, Trichuris muris, Trichuris arvicolae, and Trichuris skrjabini was
      carried out. A common homology zone was detected in the ITS1 sequence of all
      species of trichurids.

PMID- 17004100
TI  - Mitigation of radiation-induced optic neuropathy in rats by ACE inhibitor
      ramipril: importance of ramipril dose and treatment time.
AB  - PURPOSE: Radiation-induced optic nerve damage was reduced by ramipril, a prodrug
      angiotensin-converting enzyme inhibitor (ACEI). This study was to determine the
      optimum dose and administration time of ramipril for mitigating radiation-induced
      optic neuropathy. MATERIALS AND METHOD: Adult Fischer 344 male rats were treated
      with a single dose radiation 30 Gy by using radiosurgical technique. After
      irradiation, the animals were randomly assigned into groups of different ramipril
      doses and administration time; control (no treatment), radiation alone,
      radiation+ramipril in different doses and starting times of drug. Ramipril was
      given 0.5-1.5 mg/kg/day and AT1R blocker Losartan 20 mg/kg/day in drinking water
      for 180 days. Functional endpoint with visual evoked potential (VEP) and
      anatomical endpoint with gross and histological analysis with immunohistochemical
      (IHC) stain were used. RESULTS: Normal VEP measurements in un-irradiated rats
      were 46.2+/-7.9 ms. There was no change of VEP value until 4 months, but was
      lengthened to 188.1+/-58.7 ms at 6 months after radiation. By ramipril treatment
      with the dose of 1.5 mg starting at 2 weeks after radiation, VEP was
      significantly shortened to 105.7+/-88.5 ms at 6 months. Gross and microscopic
      structure of the irradiated optic nerve was well preserved in the ramipril
      treated group. CONCLUSION: Ramipril can mitigate the radiation-induced optic
      nerve damage and preserve the functional integrity of the nerve. The results
      support early treatment with a high dose of ramipril after radiation.

PMID- 17004101
TI  - MRI findings of malignant transformation of epidermoid cyst: case report.
AB  - Malignant transformation of epidermoid cysts into squamous cell carcinoma (SCC)
      rarely occurs. A 67-year-old man initially presented with an 8-year history of
      right trigeminal neuralgia. His symptoms had changed into right facial anesthesia
      with right-ear hearing impairment 8 months before first consulting a neurosurgeon
      at our hospital. Results obtained using MRI suggested an epidermoid cyst in the
      right cerebellopontine angle, but showed atypical findings of a small enhancing
      nodule in the periphery and surrounding edema in the cerebellum and pons. Surgery
      was performed to remove the mass, but a small nodule was not reached. Despite
      stereotactic radiosurgery, the patient's clinical course deteriorated; he died 13
      months after the first MRI examination. Autopsy revealed SCC originating from the
      epidermoid cyst. We present serial MRI and pathologic findings in the early and
      terminal phases of this patient.

PMID- 17004102
TI  - Acute morphological sequelae of photodynamic therapy with 5-aminolevulinic acid
      in the C6 spheroid model.
AB  - OBJECTIVE: Aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) may
      represent a treatment option for malignant brain tumors. We used a three
      dimensional cell culture system, the C6 glioma spheroid model, to study acute
      effects of PDT and how they might be influenced by treatment conditions. METHODS:
      Spheroids were incubated for 4 h in 100 microg/ml ALA in 5% CO(2) in room air or
      95% O(2) with subsequent irradiation using a diode laser (lambda = 635 nm, 40
      mW/cm(2), total fluence 25 J/cm(2)). Control groups were "laser only", "ALA
      only", and "no drug no light". Annexin V-FITC, a marker used for detection of
      apoptosis, propidium iodide (PI), a marker for necrotic cells and H 33342, a
      chromatin stain, were used for morphological characterization of PDT effects by
      confocal laser scanning and fluorescence microscopy. Hematoxylin-eosin staining
      and TdT-FragEL (TUNEL) assay were used on cryosections. Growth kinetics were
      followed for 8 days after PDT. RESULTS: PDT after incubation in 5% CO(2) provided
      incomplete cell death and growth delay in spheroids of >350 microm diameter.
      However, complete cell death and growth arrest occurred in smaller spheroids
      (<350 microm). Incubation in 95% O(2) with subsequent PDT resulted in complete
      cell death and growth arrest regardless of spheroid size. In incompletely damaged
      spheroids viable cells were restricted to spheroid centers. The rate of cell
      death in all control groups was negligible. Cell death was accompanied by
      annexin/PI costaining, but there was also evidence for annexin V-FITC staining
      without PI uptake. CONCLUSIONS: PDT of experimental glioma results in rapid and
      significant cell death that could be verified as acute necrosis immediately after
      irradiation. This effect depended on O(2) concentration and spheroid size.

PMID- 17004103
TI  - Expression of nine tumour antigens in a series of human glioblastoma multiforme:
      interest of EGFRvIII, IL-13Ralpha2, gp100 and TRP-2 for immunotherapy.
AB  - In this study, we investigated the mRNA and protein expression of nine tumour
      antigens in human glioblastoma multiforme with a view to their possible use in
      dendritic cell-based immunotherapy. Expression of ALK, EGFRvIII, GALT3, gp100, IL
      13Ralpha2, MAGE-A3, NA17-A, TRP-2 and tyrosinase were studied by real-time RT-PCR
      on frozen tissues using a series of 47 tumour samples from patients with
      glioblastoma. Results were compared with non-neoplastic brain expression or
      glioblastoma samples with very low levels of expression near the limits of
      detection for EGFRvIII and MAGE-A3, as these latter two antigens were not
      detected in non-neoplastic brain. Tumour antigens showing a 5-fold increase in
      mRNA expression were considered as positive, and only antigens displaying an mRNA
      over-expression in a significant number of cases were analysed by
      immunohistochemistry on paraffin-embedded sections. Using real time RT-PCR, we
      found EGFRvIII, gp100, IL-13Ralpha2 and TRP-2 to be positive in 64, 38, 32 and
      21% of cases, respectively. While we observed no over-expression for ALK, GALT3
      and tyrosinase, 3 samples out of 47 were positive for MAGE-3 and 1 sample for
      NA17-A. More than 25% of tumour cells showed strong protein expression in 13, 34,
      85 and 96% of GBM samples for gp100, TRP-2, EGFRvIII and IL-13Ralpha2,
      respectively. Interestingly, protein expression of at least 3 antigens was
      observed in 38% of cases. These results point out the importance of EGFRvIII, IL
      13Ralpha2 and, to a less extent gp100 and TRP-2, for developing an immunotherapy
      strategy against glioblastoma.

PMID- 17004104
TI  - Fluvastatin enhancement of trastuzumab and classical cytotoxic agents in defined
      breast cancer cell lines in vitro.
AB  - The combination of anticancer drugs used in the clinic has been based upon
      empiricism, and the potential permutations of currently available drugs overwhelm
      the clinical trials system. Recently, investigators have suggested that the
      combination of a blockade of vital signal transduction pathways in combination
      with more standard therapy might enhance anticancer effect. Using a panel of
      breast cancer cell lines and isobologram median effect analysis, a method of
      determining synergism or antagonism of drugs, we have investigated in vitro
      potentially clinically useful combinations of agents with the human cell lines
      MCF7/wt, MCF7/adr, BT474, and SK-BR-3 grown in log phase. Results were confirmed
      by curve shift analysis. Cells were exposed to the agent(s) for 72 h and then
      analyzed for cytotoxicity using a MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyl
      tetrazolium bromide) assay. Fluvastatin, an inhibitor of prenylation with
      excellent tolerability in man, was chosen to disrupt signal transduction pathways
      and thus potentially enhance the effect of more traditional anticancer agents.
      Anticancer agents tested were cytotoxics used in the treatment of breast cancer,
      trastuzumab, and rapamycin as an inhibitor of the AKT pathway. Fluvastatin
      combined with trastuzumab demonstrates global synergy of cytotoxic effect that is
      confirmed by apoptosis assay. These effects could only be partially reversed by
      adding farnesol or geranylgeraniol to restore prenylation. Epirubicin is also
      synergistic with fluvastatin in three of the four cell lines. Rapamycin, an
      inhibitor of MTOR, was synergistic with fluvastatin in two of the four cell lines
      and antagonistic in two other cell lines. The combination of fluvastatin or
      another inhibitor of prenylation and trastuzumab may be attractive for clinical
      development as the effect of trastuzumab in Her2/neu positive breast tumors is
      incomplete as a single agent.

PMID- 17004105
TI  - Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and
      proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD
      PCR and proteomics.
AB  - The ubiquitin-proteasome system facilitates the degradation of damaged proteins
      and regulators of growth and stress response. Alterations in this proteolytic
      system are associated with a variety of human pathologies. By restriction
      fragment differential display polymerase chain reaction (RFDD-PCR) and matrix
      assisted laser desorption/ionization tandem time-of-flight mass spectrometry
      (MALDI-TOF-TOF MS) based on two-dimensional polyacrylamide gel electrophoresis (2
      DE), differentially expressed genes and proteins of ubiquitin specific proteases
      (USPs), proteasome subuinits (PSs) and ubiquitin protein ligase E3A (UBE3A) were
      analyzed between breast cancer and adjacent normal tissues. Some of them were
      further verified as over-expression by immunohistochemical stain. Five genes of
      proteasome subunits (PSs), including PSMB5, PSMD1, PSMD2, PSMD8 and PSMD11, four
      genes of USPs, including USP9X, USP9Y, USP10 and USP25, and ubiquitin protein
      ligase E3A (UBE3A) were over-expressed (>3-fold) in breast cancer tissue compared
      to adjacent normal tissue, and over-expression (>4-fold) of proteins of PSMA1 and
      SMT3A were observed in breast cancer tissue. PSMD8, PSMD11 and UBE3A were further
      verified as over-expression by immunohistochemical stain. The action of ubiquitin
      proteasome system were obviously enhanced in breast cancer, and selectively
      intervention in action of ubiquitin-proteasome system may be a useful method of
      treating human breast cancer.

PMID- 17004106
TI  - MDA-MB-435 cells are derived from M14 melanoma cells--a loss for breast cancer,
      but a boon for melanoma research.
AB  - BACKGROUND: The tissue of origin of the cell line MDA-MB-435 has been a matter of
      debate since analysis of DNA microarray data led Ross et al. (2000, Nat Genet
      24(3):227-235) to suggest they might be of melanocyte origin due to their
      similarity to melanoma cell lines. We have previously shown that MDA-MB-435 cells
      maintained in multiple laboratories are of common origin to those used by Ross et
      al. and concluded that MDA-MB-435 cells are not a representative model for breast
      cancer. We could not determine, however, whether the melanoma-like properties of
      the MDA-MB-435 cell line are the result of misclassification or due to
      transdifferention to a melanoma-like phenotype. METHODS: We used karyotype,
      comparative genomic hybridization (CGH), and microsatalite polymorphism analyses,
      combined with bioinformatics analysis of gene expression and single nucleotide
      polymorphism (SNP) data, to test the hypothesis that the MDA-MB-435 cell line is
      derived from the melanoma cell line M14. RESULTS: We show that the MDA-MB-435 and
      M14 cell lines are essentially identical with respect to cytogenetic
      characteristics as well as gene expression patterns and that the minor
      differences found can be explained by phenotypic and genotypic clonal drift.
      CONCLUSIONS: All currently available stocks of MDA-MB-435 cells are derived from
      the M14 melanoma cell line and can no longer be considered a model of breast
      cancer. These cells are still a valuable system for the study of cancer
      metastasis and the extensive literature using these cells since 1982 represent a
      valuable new resource for the melanoma research community.

PMID- 17004107
TI  - Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her
      2/neu.
AB  - Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for
      the treatment of Her-2/neu-positive human cancer. Amplification and/or over
      expression of Her-2/neu occur in multiple human malignancies and are associated
      with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer
      immunotherapy. We have developed and characterized a murine monoclonal anti-Id
      antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a
      surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor
      vaccine was evaluated in a murine tumor model. Immunization of immunocompetent
      C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with
      Freund's adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as
      well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells,
      SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow
      cytometry. Flow cytometry analysis also demonstrated strong reactivity of
      immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but
      no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular
      cytotoxicity against EL4-Her-2 cells was also observed in presence of immune
      sera. Mice immunized with 6D12 were protected against a challenge with lethal
      doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4
      cells or when mice were immunized with an unrelated anti-Id antibody and
      challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can
      induce protective Her-2/neu specific antitumor immunity and may serve as a
      potential network antigen for the treatment of patients with Her-2/neu-positive
      tumors.

PMID- 17004108
TI  - The 3' untranslated region C > T polymorphism of prohibitin is a breast cancer
      risk modifier in Polish women carrying a BRCA1 mutation.
AB  - The variable penetrance of breast cancer in BRCA1 mutation carriers suggests that
      other genetic or environmental factors modify breast cancer risk. The C to T
      transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA
      function and has been shown to be associated with an increased breast cancer risk
      among young North-American women who have one first-degree relative with breast
      cancer. To investigate whether the PHB 3'UTR polymorphism acts as a modifier of
      hereditary breast cancer risk we performed a case-control study among female
      BRCA1 mutation carriers, which included 258 cases and 258 controls who were
      unaffected by ovarian cancer, in situ breast carcinoma or any other type of
      cancer. Controls were matched to cases by year of birth and BRCA1 mutation
      (5382insC, 300 T > G, 4153delA). Genotyping analysis was performed using RFLP
      PCR. Odds ratios (OR) were calculated using conditional and penalised univariable
      and multivariable logistic regression. Multivariable penalised logistic
      regression revealed CT (OR(adj), 2.03; 95% CI, 1.17-3.59) and combined CT + TT
      (OR(adj), 2.12; 95% CI, 1.23-3.70) genotypes as significant modifiers of breast
      cancer risk. Breast cancer risk did not differ between carriers of the 300 T > G
      and 5382insC mutation. Our results suggest that the PHB 3'UTR T allele increases
      the risk of breast cancer in patients who are already at increased risk of
      disease.

PMID- 17004110
TI  - A comprehensive expression survey of bone morphogenetic proteins in breast cancer
      highlights the importance of BMP4 and BMP7.
AB  - Bone morphogenetic proteins (BMPs) regulate diverse cellular processes, such as
      proliferation, differentiation, and apoptosis. The BMPs have been studied in
      several cancers, but thus far contradictory results have been obtained and,
      especially in breast cancer, information on BMPs is still limited. We performed a
      systematic expression survey of BMPs and their receptors in breast cancer. mRNA
      expression was studied of seven BMP ligands (BMP2-BMP8) and six receptors (ACVR1,
      BMPR1A, BMPR1B, BMPR2, ACVR2A, and ACVR2B) that specifically mediate BMP signals.
      Expression levels were determined in 22 breast cancer cell lines, 39 primary
      breast tumors, normal human mammary epithelial cell line, and normal mammary
      gland using semiquantitative RT-PCR. The expression frequencies and expression
      levels of different BMPs varied considerably in breast cancer with BMP4 and BMP7
      being most frequently expressed and showing highest expression levels. The BMP
      specific receptors were more uniformly expressed and indicated that breast cancer
      is fully capable of transmitting BMP signals. Expression frequencies and levels
      for both the ligands and the receptors were in good concordance between the
      breast cancer cell lines and primary tumors. We can conclude that breast cancers
      possess functional BMP signaling machinery on the cell surface with distinct
      differences in the expression of various BMP ligands. Our survey focuses the
      attention particularly toward BMP4 and BMP7 and suggests their importance in
      breast cancer. Breast cancer cell lines and the data generated here serve as a
      good resource for further studies on BMP function in breast cancer.

PMID- 17004111
TI  - Association between reproductive factors and breast cancer survival in younger
      women.
AB  - This analysis investigated whether reproductive factors such as age at menarche,
      parity, and timing and outcomes of pregnancies were associated with survival
      among women with breast cancer younger than 55 years. Female residents of
      Atlanta, Georgia, and central New Jersey who were diagnosed with a primary,
      incident invasive breast cancer between 1990 and 1992 and enrolled in a
      population-based study (n = 1,264) were followed for 8-10 years. Detailed
      exposure and covariate information was collected via in-person interviews
      administered shortly after diagnosis. Vital status as of January 1, 2000 was
      ascertained through the National Death Index via the state cancer registries (n =
      292 deaths). Cox regression methods were used to estimate hazard ratios (HR) and
      95% confidence intervals (CI) adjusted for confounders. Parity of 4 or more
      births, as compared with nulliparity, was positively associated with all-cause
      mortality, [HR (95% CI) = 1.71 (1.09-2.67)]. Increased mortality was associated
      with having given birth within 5 years prior to diagnosis (<or=5 vs. >5 years)
      [1.78 (1.28-2.47)], and was more pronounced among women with a pre-diagnostic
      body mass index of <25 kg/m2 [2.54 (1.61-4.00)]. Early age at menarche and early
      age at first birth also modestly increased mortality; history of miscarriage,
      induced abortion, and ever breastfeeding were not related to survival. These
      results may help elucidate breast cancer progression mechanisms and enable a
      better understanding of how reproductive characteristics influence breast cancer
      survival.

PMID- 17004109
TI  - A strong association between body fat mass and protein profiles in nipple
      aspirate fluid of healthy premenopausal non-lactating women.
AB  - Fluid can be aspirated from the nipples of most non-lactating women. This nipple
      aspirate fluid (NAF) is a potential source for the discovery of new breast cancer
      biomarkers. NAF has two distinct protein profiles. Type I NAF is similar to the
      fluid associated with cystic disease of the breast, whereas type II NAF is
      enriched in milk-associated proteins. The prevalence of these two profiles
      differs in healthy women and in breast cancer patients. This study investigated
      the relationship of these two NAF profiles to reproductive history, body
      composition, diet, and levels of lipids, steroids and thyroid hormones in healthy
      premenopausal women (age 30-40 years) who had regular menstrual cycles and normal
      mammograms and were not taking contraceptive medications. On average, women with
      the type I NAF profile were older, had more years since last childbirth, were
      less likely to have breastfed their babies and had higher dietary saturated fat
      intake, body mass index, body fat mass, and levels of plasma low density
      lipoproteins than women with the type II profile (P <0.05). Using multiple
      logistic regression, type I NAF was predicted independently (P <0.05) by higher
      body fat mass [Odds Ratio (OR) = 3.0; 95% Confidence Interval (CI): 1.5-6.1],
      more years since last childbirth (OR = 2.6; 95% CI: 1.3-5.2) and a higher
      percentage of calories from saturated fat (OR = 4.1; 95% CI: 1.1-14.6). These
      results suggest that protein profiles of NAF might be influenced by amounts or
      types of dietary and body fat, but further study of the relationship of the two
      profiles to breast cancer risk is needed.

PMID- 17004112
TI  - AZD3409 inhibits the growth of breast cancer cells with intrinsic resistance to
      the EGFR tyrosine kinase inhibitor gefitinib.
AB  - AKT and MAPK signaling are involved in the resistance of breast cancer cells to
      the EGFR tyrosine kinase inhibitor gefitinib. RAS proteins are upstream mediators
      that transfer messages from surface receptors to intracellular signal transducers
      including MAPK and AKT pathways. AZD3409 is a novel prenyl inhibitor that has
      shown activity against both farnesyl transferase and geranylgeranyl transferase
      in isolated enzyme studies. We explored the activity of AZD3409 on breast cancer
      cell lines with high (SK-Br-3), intermediate (MDA-MB-361) or low (MDA-MB-468)
      sensitivity to gefitinib. We found that AZD3409 inhibits the growth of breast
      cancer cells in a dose-dependent manner, with the MDA-MB-468 and MDA-MB-361 cell
      lines showing higher sensitivity as compared with SK-Br-3 cells. Treatment with
      AZD3409 produced a significant reduction in the levels of activation of AKT in
      the three cell lines. AZD3409 also induced an increase in the expression of
      p27kip-1 and of hypophosphorylated forms of pRb2 in MDA-MB-468 cells that was
      associated with accumulation of cells in G0/G1 and the appearance of a sub-G1
      peak suggestive of apoptosis. In contrast, AZD3409 produced a G2 arrest
      associated with reduced expression of pRb2 in MDA-MB-361 cells. A synergistic
      anti-tumor effect was observed when MDA-MB-468 or MDA-MB-361 cells were treated
      with both AZD3409 and gefitinib, whereas this combination was only additive in SK
      Br-3 cells. However, treatment of breast cancer cells with AZD3409 and gefitinib
      did not produce a more significant blockade of AKT signaling as compared with
      gefitinib alone. These data suggest that AZD3409 might be active in gefitinib
      resistant breast carcinoma.

PMID- 17004113
TI  - A comprehensive examination of CYP19 variation and risk of breast cancer using
      two haplotype-tagging approaches.
AB  - BACKGROUND: Numerous studies point to a positive relationship between elevated
      levels of estrogens and increased risk of breast. Androgens are converted to
      estrogens by the aromatase enzyme, which is encoded by the CYP19 gene. We
      recently published resequencing data on 88 polymorphisms identified in that gene.
      The hypothesis tested in this study was that polymorphisms, or haplotypes, in
      CYP19 are related to risk of breast cancer. METHODS: Incident cases of breast
      cancer were identified through the Division of Medical Oncology at the Mayo
      Clinic in Rochester, MN. Controls were patients visiting Mayo for an annual
      medical examination. Controls were frequency matched to cases based on age and
      region of residence. Tag-polymorphisms were selected using 2 methods: (1) 12
      variants using the tag-selection method of Carlson et al. (Am J Hum Genet 74:106
      120, 2004); and (2) 12 variants using the haplotype method of Stram (Genet
      Epidemiol 27:365-374, 2004). Six SNPs were selected by both methods. Genotyping
      was conducted using SNPStream, TaqMan and RFLP analyses. Logistic regression was
      used to calculate odds ratios (OR) and 95% confidence intervals (CI). Analyses
      were conducted among all cases and controls, or stratified by estrogen receptor
      alpha (ER) status and/or menopausal status. RESULTS: A total of 750 cases (60%
      postmenopausal) and 732 controls (75% postmenopausal) were included. No
      association with breast cancer risk was detected for individual variants,
      selected tagSNPs or hap-tag SNPs despite 80% power to detect OR as low as 1.49
      for minor allele frequency (MAF) of 0.10. Similarly, stratified analyses based on
      ER status or menopausal status failed to detect any association with breast
      cancer risk. CONCLUSION: These analyses suggest that variants of CYP19 are not
      associated with risk of breast cancer.

PMID- 17004114
TI  - Bad expression predicts outcome in patients treated with tamoxifen.
AB  - AIMS: Activation of the PI3K/Akt signal transduction pathway has been linked to
      endocrine resistance in tamoxifen treated breast cancer patients. Activation of
      the PI3K/Akt pathway causes phosphorylation of Bad leading to modulation of
      cellular apoptosis. The present study was carried out to test the hypothesis that
      disruption of apoptosis in breast cancer, via Akt activation, is linked with
      hormone resistance. METHODS: Immunohistochemistry (IHC) was performed on 402
      oestrogen receptor (ER) positive breast cancers using antibodies against Bad,
      pBad (ser 112), Bcl-2, Bcl-xl and Bax. RESULTS: Bad, pBad (ser 112), Bcl-2 and
      Bax expression was observed in the cellular cytoplasmic compartment only.
      Patients, whose tumours had high levels of Bad expression, had a significantly
      improved disease-free survival when compared to patients whose tumours had low
      levels of Bad expression (P = 0.049). Activation of the PI3K/Akt pathway by
      either heregulin or oestrogen had no effect on expression of Bad, Bcl-2, Bax or
      Bcl-xl. However, heregulin increased pBad (ser 112) expression. DISCUSSION: Data
      presented here shows that Bad expression is associated with relapse in tamoxifen
      treated breast cancer patients, supporting our hypothesis that the apoptosis
      pathway is involved in tamoxifen resistance.

PMID- 17004115
TI  - Effect of undertreatment on the disparity in age-related breast cancer-specific
      survival among older women.
AB  - OBJECTIVES: Assess the relationship between age and breast cancer-specific
      survival among older women and determine whether the observed age-related
      disparities in survival is explained by differences in breast cancer treatments
      received. METHODS: Women > or =65 years old at diagnosis with stage I-IIIA breast
      cancer diagnosed between 1997 and 1998 were recruited from four regions of the
      United States and followed prospectively for 5 years after diagnosis. Data was
      obtained from tumor registries, medical records, and telephone interviews. The
      primary endpoint was breast cancer-specific survival. Our independent variables
      were age operationalized as < or =75 years vs. >75 years, and receipt of
      recommended guideline therapy, adapted from the National Institutes of Health
      guideline consensus conference. RESULTS: Of 689 women, 36% were >75 years. Women
      >75 years were less likely to have received the following; axillary lymph node
      dissection (84% vs. 93%, P = 0.0003), radiotherapy (40% vs. 54%, P = 0.0003),
      definitive primary therapy (71% vs. 84%, P < 0.0001), chemotherapy (9% vs. 28%, P
      < 0.0001), and guideline therapy (31% vs. 54%, P < 0.0001). The 5-year breast
      cancer-specific survival was 95% (95% confidence interval [CI], 90%, 97%) for
      those < or =75 years who received guideline therapy, 94% (95% CI, 90%, 97%) for
      those < or =75 years who did not receive guideline therapy, 96% (95% CI, 88%,
      99%) for those >75 years who received guideline therapy and 83% (95% CI, 74%,
      89%) for those >75 years who did not receive guideline therapy, (P = 0.002) by
      the log-rank test. CONCLUSION: Receipt of guideline therapy may reduce the age
      related disparity in breast cancer survival among older women.

PMID- 17004116
TI  - Cost-effectiveness of different reading and referral strategies in mammography
      screening in the Netherlands.
AB  - In mammography screening with double reading, different strategies can be used
      when the readers give discordant recommendations for referral. We investigated
      whether the results of the Dutch breast cancer screening programme can be
      optimised by replacing the standard referral strategy by consensus. Twenty-six
      screening radiologists independently and blinded to outcome read a test set
      consisting of previous screening mammograms of 250 cases (screen-detected and
      interval cancers) and 250 controls. Their referral recommendations were paired
      and, in case of discrepancy, re-read according to three referral strategies: (1)
      decision by one of the readers; (2) arbitration by a third reader; (3) referral
      if both readers agree (consensus). Data allowed studying other referral
      strategies, including referral if any reader suggests, as well. Double reading
      with referral if any reader suggests resulted in a 1.03 times higher sensitivity
      (76.6%) and a 1.31 times higher referral rate (1.26%) than double reading with
      consensus. To estimate the cost-effectiveness, the outcomes were used in a
      microsimulation model. Even if double reading with referral if any reader
      suggests results in four times as high referral rates and an accompanying
      increase of biopsies or other invasive procedures, the cost-effectiveness of
      4,190 Euros per life-year gained may well be in the range of acceptable cost
      effectiveness for Dutch health care programmes.

PMID- 17004117
TI  - Differences in HIV risk behaviors by gender in a sample of Tanzanian injection
      drug users.
AB  - This study investigated differences in drug use and sexual behaviors among from
      237 male and 123 female heroin users in Dar es Salaam, Tanzania. Multivariate
      models of risk of needle sharing were estimated using multivariate logistic
      regression. Men were significantly older, more likely to inject only white
      heroin, share needles, and give or lend used needles to other injectors. Women
      were more likely to be living on the streets, have injected brown heroin, have
      had sex, have had a higher number of sex partners, and have used a condom with
      the most recent sex partner. Being male and earning less than US $46 in the past
      month were significant predictors of increased risk of needle sharing. Despite
      differences in sociodemographic, drug use, and sexual behaviors by gender, both
      male and female injectors in Dar es Salaam exhibit elevated risk of HIV infection
      associated with drug use.

PMID- 17004118
TI  - Comparing functional assessment methodologies: a quantitative synthesis.
AB  - There has been much research concerning functional assessment over the past 20
      years, but several important research considerations have yet to be explained.
      One is the comparison of different types of functional assessment (e.g.,
      experimental functional analysis and non-experimental functional assessment). The
      current study aims to compare the different methodologies of functional
      assessment and their effectiveness in ascribing function to a target behavior and
      in the treatment selection that follows such an assessment. Quantitative
      synthesis data were used to answer questions regarding behavioral function,
      assessment type, and treatment effectiveness. Results indicate that assessment
      type can impact treatment effectiveness and that there is a relationship between
      behavior type and ascribed function.

PMID- 17004119
TI  - Patterns of nonverbal cognitive functioning in young children with autism
      spectrum disorders.
AB  - Previous research demonstrates an uneven pattern of cognitive abilities in
      children with autism spectrum disorders (ASDs). This study examined whether this
      uneven pattern exists within the nonverbal domain in young children. We
      hypothesized relative strengths in perceptual abilities and weaknesses in
      nonverbal conceptual abilities in preschoolers with ASDs compared to groups with
      non-autism developmental delays and typical development. Profiles were examined
      using the Leiter International Performance Scale-Revised. The ASD group displayed
      clear relative strengths in visuospatial disembedding and detail-focused
      processing, with relative weaknesses in abstraction and concept formation. This
      contrasted with patterns of roughly equivalent abilities in both comparison
      groups. These findings have implications for subsequent development and may
      represent key features of the cognitive profile of autism.

PMID- 17004120
TI  - Systematic screening for subtelomeric anomalies in a clinical sample of autism.
AB  - High-resolution karyotyping detects cytogenetic anomalies in 5-10% of cases of
      autism. Karyotyping, however, may fail to detect abnormalities of chromosome
      subtelomeres, which are gene rich regions prone to anomalies. We assessed whether
      panels of FISH probes targeted for subtelomeres could detect abnormalities beyond
      those identified by karyotyping in 104 individuals with Pervasive Developmental
      Disorders (PDDs) drawn from a general clinical population. Four anomalies were
      detected by karyotyping, while no additional anomalies were detected by
      subtelomere FISH or by probes targeted for 15q11.2q13 or 22q11.2 in subgroups of
      our sample. We conclude that while karyotyping may be more broadly indicated for
      autism than previously supposed, subtelomere FISH appears less likely to be a
      useful screening tool for unselected PDD populations.

PMID- 17004121
TI  - Esophageal acid exposure in upright and recumbent postures: roles of lower
      esophageal sphincter, esophageal contractile and transport function, hiatal
      hernia, age, sex, and body mass.
AB  - This study aimed to assess, using multiple regression analyses, the roles of
      lower esophageal sphincter, esophageal contractile and transport function, hiatal
      hernia, age, sex, and body mass for esophageal acid exposure in upright and
      recumbent postures and for esophagitis. In 116 patients with reflux symptoms,
      acid exposure was recorded by 24-hr pH monitoring, motility manometrically, bolus
      transport scintigraphically, hiatal hernia and esophagitis endoscopically. In
      upright posture, the percentage time at pH <4 increased significantly with higher
      body mass index and lower distal esophageal amplitude, the number of episodes >5
      min at pH <4 with lower distal amplitude, slower transport, and higher body mass,
      and the longest episode at pH <4 with lower distal amplitude. In recumbency, the
      percentage time at pH <4 increased with lower percentage of effective esophageal
      contraction waves and male sex, and the number of episodes and the longest
      episode with lower percentage effective waves. The severity of esophagitis
      augmented with slower supine transport and male sex. In both postures, acid
      exposure and esophagitis seem to be determined primarily by impaired esophageal
      motility and the ensuing slow bolus transport rather than by compromised lower
      esophageal sphincter function and the presence and size of a hiatal hernia.

PMID- 17004122
TI  - Glucagon for the relief of esophageal food impaction does it really work?
AB  - We sought to evaluate our experience with glucagon used in the emergency
      department setting to relieve esophageal food impaction (EFI). We reviewed the
      records of patients with food impaction who received glucagon between January
      1998 and May 2003 and recorded patient demographics, medical history, symptoms
      following glucagon administration, and endoscopic findings. There were 92
      episodes of food impaction in 85 patients. Thirty-three percent of the episodes
      resulted in resolution of symptoms following a dose of glucagon. Sixty-seven
      percent had symptoms of food impaction after glucagon and underwent upper
      endoscopy in the emergency room. Only previous solid food dysphagia was
      positively associated with response to glucagon. Patients who received glucagon
      plus a benzodiazepine were more likely to have resolution of the EFI. In our
      experience, glucagon appears to relieve food impaction in one third of patients
      treated. This result is comparable to previously published data examining
      glucagon and placebo. The lack of advantage over placebo questions the practice
      of glucagon administration for EFI.

PMID- 17004123
TI  - A retrospective search for predictors of clinical response to selective
      granulocyte and monocyte apheresis in patients with ulcerative colitis.
AB  - Recently, selective granulocytapheresis (Adacolumn) has appeared as a new
      treatment for patients with inflammatory bowel disease. This study sought to
      determine predictors of response to this new nonpharmacologic mode of therapy by
      retrospectively evaluating 28 patients who received granulocytapheresis after
      experiencing active ulcerative colitis (UC). Between April 2000 and March 2004,
      28 consecutive patients received granulocytapheresis for active UC with the
      Adacolumn, which is filled with cellulose acetate beads as the column
      leukocytapheresis carriers; the carriers adsorb granulocytes,
      monocytes/macrophages, and a small fraction of lymphocytes (FcgammaR and
      complement receptors bearing leukocytes). Each patient could receive up to 10
      Adacolumn sessions, at 2 sessions per week. In 2004, clinical response was
      retrospectively evaluated. Seven days after the last Adacolumn session, 20 of 28
      patients had remission (colitis activity index [CAI] < or =4) including all 8
      patients who had their first UC episode. The mean duration of UC in the 8 first
      episode cases was 3.4 months compared with 40.2 months for all 28 patients and
      65.4 months for the 8 nonresponders. The response to Adacolumn was independent of
      basal CAI. The 8 nonresponders were given conventional medication (CM) or
      cyclosporine (CsA) if the former failed. Two responded to CM, 3 to CsA, and 3
      underwent colectomy. First UC episode and short disease duration appear good
      predictors of response to granulocytapheresis. Selective granulocytapheresis
      might be an effective first-line treatment.

PMID- 17004124
TI  - Sustained viral response to pegylated interferon alpha-2b and ribavirin in
      chronic hepatitis C refractory to prior treatment.
AB  - Hepatitis C virus (HCV) infection refractory to previous therapy is common.
      Treatment of patients with refractory disease is difficult and less studied.
      Pegylated interferon alpha-2b plus ribavirin is used for treatment of HCV
      patients naive to therapy. We conducted a randomized study for refractory HCV
      patients using a high- vs. a low-dose pegylated interferon alpha-2b and ribavirin
      protocol. Our aim was (1) to determine the efficacy of pegylated interferon alpha
      2b plus ribavirin to eradicate HCV in previously treated individuals and (2) to
      compare a low-dose to a high-dose regimen. One hundred fifty-two patients were
      initiated in the study, 112 (74%) were male and 40 (26%) female. Nineteen percent
      of patients obtained a sustained viral response (SVR) in the high-dose arm. Prior
      relapsers had the highest SVR rates: 50% in non-genotype 1 and 34% in genotype 1.
      The odds of achieving a SVR were six times higher in previous relapsers. The rate
      of SVR in genotype 1 patients who were nonresponders to prior therapy was only
      8%. All patients who achieved a SVR had no detectable virus at week 24. However,
      only half of those who had undetectable viral titers at week 24 achieved a SVR.
      In conclusion, retreatment of patients with refractory hepatitis C infection with
      interferon alpha-2b and ribavirin combination therapy is well tolerated and gives
      modest response rates. The most important factor in predicting response to
      therapy is the manner of response to previous treatment. The likelihood of
      response to treatment can be predicted from the viral titers at 24 weeks.

PMID- 17004126
TI  - Can community change be measured for an outcomes-based initiative? A comparative
      case study of the success by 6 initiative.
AB  - One of the challenges facing nonprofit organizations today is the demand for
      measurable results. Increasingly, these organizations are focusing less on
      program outputs and program outcomes in favor of community outcomes or changes
      demonstrated in the larger community. Success by 6(R) is a popular United Way
      initiative that emphasizes defining and measuring community outcomes. In this
      paper, we describe our work with 24 Success by 6(R) initiatives around the
      country. It is clear that not all of these initiatives are measuring community
      outcomes. Of those initiatives that are experiencing some success measuring
      community outcomes, similar measurement strategies are reported. Additionally,
      our experience suggests several United Way employees express dissatisfaction with
      the logic model as a framework for defining and measuring community outcomes
      although no preferred alternative model is identified. Evaluators working with
      community-wide initiatives must find ways to communicate the differences between
      program and community outcomes to key stakeholders and funders.

PMID- 17004125
TI  - Improving data reliability using a non-compliance detection method versus using
      pharmacokinetic criteria.
AB  - Data from clinical trials present numerous problems for the data analyst. These
      include non-compliance with the prescribed dosing regimen and inaccurate
      recollection of dosing history by patients as well as mistakes in recording data.
      Several methods have been proposed to address these issues. One such technique by
      Lu et al. (Selecting reliable pharmacokinetic data for explanatory analyses of
      clinical trials in the presence of possible noncompliance. J. Pharmacokinet.
      Pharmacodyn. 28:343-362 (2001)) identifies occasions in pharmacokinetic (PK) data
      where the preceding dosing history is likely to be unreliable. We used this
      method, implemented in the software program NONMEM (beta) VI, to clean a dataset
      containing indinavir (IDV) plasma concentrations from HIV-1 infected patients.
      The data was also cleaned by inspection in Microsoft Excel using clinical PK
      criteria. A one-compartment model with first order absorption and elimination was
      fit to both sets of cleaned data. IDV population PK parameters obtained from
      these analyses were similar to those reported previously. It is established that
      IDV nephrotoxicity is related to high IDV exposure. However, no relationships
      were found between any PK parameters and nephrotoxicity in the "compliance
      cleaned" dataset. In the "PK cleaned" dataset, the oral clearance and apparent
      volume were lower by 9.1% and 6.6%, respectively in patients with any type of
      nephrotoxicity and the maximum IDV concentration (C(max)) was 12.1% higher. In
      patients suffering from nephrolithiasis in particular, C(max) was 15.5% higher.
      Accordingly, the use of the non-compliance detection method did not improve the
      reliability of our dataset over the usual method of applying clinical criteria.
      In fact, analyses on the compliance-cleaned dataset missed some exposure-toxicity
      relationships. Thus, automated methods must be tested rigorously with 'real life'
      datasets, used with caution, and always in conjunction with clinical reasoning to
      avoid overlooking a signal in noisy data.

PMID- 17004127
TI  - The effects of cumulative risks and promotive factors on urban adolescent alcohol
      and other drug use: a longitudinal study of resiliency.
AB  - Resiliency theory provides a conceptual framework for studying why some youth
      exposed to risk factors do not develop the negative behaviors they predict. The
      purpose of this study was to test compensatory and protective models of
      resiliency in a longitudinal sample of urban adolescents (80% African American).
      The data were from Years 1 (9th grade) and 4 (12th grade). The study examined
      effects of cumulative risk and promotive factors on adolescent polydrug use
      including alcohol, tobacco and marijuana. Cumulative measures of risk/promotive
      factors represented individual characteristics, peer influence, and
      parental/familial influences. After controlling for demographics, results of
      multiple regression of polydrug use support the compensatory model of resiliency
      both cross-sectionally and longitudinally. Promotive factors were also found to
      have compensatory effects on change in adolescent polydrug use. The protective
      model of resiliency evidenced cross-sectionally was not supported in longitudinal
      analysis. The findings support resiliency theory and the use of cumulative
      risk/promotive measures in resiliency research. Implications focused on utilizing
      multiple assets and resources in prevention programming are discussed.

PMID- 17004128
TI  - Neurochemical changes in brain induced by chronic morphine treatment: NMR studies
      in thalamus and somatosensory cortex of rats.
AB  - To investigate the effects of chronic morphine treatment and its cessation on
      thalamus and the somatosensory cortex, an ex vivo high resolution (500 MHz) (1)H
      nuclear magnetic resonance spectroscopy (NMRS), in the present study, was applied
      to detect multiple alterations of neurochemicals and/or neurometabolites in the
      rats. Ten days of chronic morphine administration was observed to markedly
      increase the total amount of lactate (Lac), myo-inositol (my-Ins) (each P < 0.01)
      and aspartate (Asp) (P < 0.05), and significantly decrease that of glutamate
      (Glu) and glutamine (Gln) in the rats thalamus (each P < 0.05). In the
      somatosensory cortex, chronic morphine was shown to increase the level of Lac and
      my-Ins, and decrease that of Glu (each P < 0.05). Interestingly, the ratio of
      Glu/GABA was found to decrease in these two brain areas after chronic morphine
      treatment, and among the detectable neurochemicals in those two cerebral areas,
      only taurine (Tau) showed to result in a significant increment in thalamus during
      the process of morphine discontinuation (P < 0.05). Moreover, the alterations of
      multiple neurochemicals due to chronic morphine exhibited a tendency of recovery
      to the normal level over the course of morphine withdrawal. The results suggested
      that, in thalamus and the somatosensory cortex, chronic morphine administration
      and its cessation could induce multiple neurochemical changes, which may involve
      in the brain energy metabolism, activity and transition of neurotransmitters.

PMID- 17004129
TI  - The increase of choline acetyltransferase activity by docosahexaenoic acid in
      NG108-15 cells grown in serum-free medium is independent of its effect on cell
      growth.
AB  - We investigated the influence of the polyunsaturated docosahexaenoic acid (22:6n
      3; DHA) on the constitutive expression of choline acetyltransferase (ChAT) in
      native and induced expression in differentiated cholinergic cells NG108-15 grown
      in serum-free medium. Elimination of serum-derived trophic support resulted in
      growth arrest and a strong decrease of ChAT activity. In either conditions, DHA
      largely rescued general indicators of cell growth and function, and partially
      prevented the decrease of ChAT activity. However, the maximal effect on general
      cell state in native and differentiated cells, and ChAT activity in native cells,
      was reached at or below 10 mumol/l of DHA. In contrast, maximal induction of ChAT
      activity in differentiated cells required about six times higher concentrations
      of DHA. These data thus demonstrate stimulatory effect of DHA on ChAT activity
      that is independent of its general cell protective properties.

PMID- 17004130
TI  - CNTF-activated astrocytes release a soluble trophic activity for oligodendrocyte
      progenitors.
AB  - CNTF (ciliary neurotrophic factor) has been suggested to be an important survival
      factor for oligodendrocytes; however, this effect is inconsistently obtained and
      myelination appears normal in CNTF null animals. On the other hand, CNTF
      stimulates astrocytes to produce growth and trophic factors. Therefore, we tested
      the hypothesis that CNTF acts indirectly through astrocytes to promote
      oligodendrocyte survival. We show that CNTF-stimulated astrocytes release a
      trophic factor(s) that leads to more than double the number of oligodendrocyte
      progenitor cells (OPCs) by 48 h. The trophic activity fractionates at greater
      than 30 kD. By contrast, OPCs grown in CNTF supplemented chemically defined
      medium fared no better than cells grown without CNTF. Untreated astrocytes, and
      CNTF- and IL-1beta -stimulated astrocytes all promoted the proliferation of OPCs
      to a similar extent, but only the CNTF-stimulated astrocyte conditioned media
      (CM) resulted in increased OPCs numbers. Cumulatively, these results confirm
      previous data indicating that astrocytes release potent mitogens for
      oligodendroglia, and demonstrate that CNTF stimulates astrocytes to release an
      OPC survival-promoting activity.

PMID- 17004131
TI  - Increased neuronal nuclear calcium influx in neonatal seizures.
AB  - We hypothesized that neonatal seizures lead to increased Ca(2+) influx (nCa(2+)I)
      in neuronal nuclei of newborn rats and that such increase is nitric-oxide
      mediated. Neuronal nuclear (45)Ca(2+) influx (nCa(2+)I) was measured in neuronal
      nuclei of 25 10-day-old male rat-pups newborn brains. They were divided into five
      groups (n = 5/group). (I) control; (II) hypoxia without seizures; (III) hypoxia
      with seizures; (IV) kainate, 2 mg/kg intraperitoneal (i.p.)-induced seizures and
      (V) 7-nitroindazole (7-NINA), 1 mg/kg i.p. pretreated, kainate-induced seizures.
      nCa(2+)I was significantly (P < 0.05) increased following hypoxia or seizures
      (hypoxic- or kainate-induced). Post-hypoxic seizures further enhanced nCa(2+)I
      increase induced by hypoxia (P < 0.05). 7-NINA abated the nCa(2+)I increase
      induced by kainate. We conclude that (1) kainate or hypoxia-induced seizures in
      newborn rats modify the neuronal nuclear membrane function, resulting in
      increased nCa(2+)I, (2) seizures exacerbate the hypoxia-induced increased
      nCa(2+)I incurred after hypoxia and (3) intranuclear calcium surges during
      kainate-induced neonatal seizures are nitric oxide-mediated.

PMID- 17004132
TI  - L-NAME has opposite effects on the productions of S-adenosylhomocysteine and S
      adenosylmethionine in V12-H-Ras and M-CR3B-Ras pheochromocytoma cells.
AB  - Homocysteine is a sulfur-containing, nonproteinogenic, neurotoxic amino acid
      biosynthesized during methyl cycles after demethylation of S-adenosylmethionine
      (SAM) to S-adenosylhomocysteine (SAH) and subsequent hydrolysis of SAH into
      homocysteine and adenosine. Formed homocysteine is either catabolized into
      cystathionine (transsulfuration pathway) by cystathionine beta-synthase, or
      remethylated into methionine (remethylation pathway) by methionine synthase. To
      demonstrate the specificity of Ras-elicited effects on the activity of methyl
      cycles, wild-type pheochromocytoma PC12, mutant oncogenic rasH gene (MVR)
      expressing PC12 pheochromocytoma and normal c-rasH stably transfected M-CR3B
      cells were incubated with the N(omega)-nitro-L-arginine methyl ester (L-NAME),
      and manumycin, (inhibitors of nitric oxide synthase and farnesyltransferase,
      respectively). We have found that L-NAME significantly changes the SAM/SAH ratio
      in both MCR and MVR cells. Moreover, these alterations have reciprocal character;
      in the MCR cells, the SAM/SAH ratio was raised, whereas in the MVR cells this
      ratio was decreased. We conclude that depletion of endogenous NO with L-NAME
      increased the production of SAH only in cells with mutated oncogenic RasH,
      possibly through enhancement of production of reactive oxygen species (ROS).
      Oxidative stress can increase cystathionine beta-synthase activity that switches
      methyl cycles from remethylation into transsulfuration pathway to maintain the
      intracellular glutathione pool (essential for the redox-regulating capacity of
      cells) via an adaptive process.

PMID- 17004134
TI  - Fluorescence recovery under decaying photobleaching irradiation: concept and
      experiment.
AB  - A novel modification of photobleaching method for measurement of lateral
      diffusion is developed. In this approach fluorescence recovery kinetics is
      measured under decaying photobleaching irradiation, termed as fluorescence
      recovery under decaying photobleaching (FRDP). The time evolution of fluorescence
      intensity normalized to input irradiation starts from the photobleaching kinetics
      and transforms into the kinetics of fluorescence recovery at a later stage
      resulting in appearance of minimum. The analytical solution for the kinetics of
      fluorescence for Gaussian lineshape of laser beam and hyperbolic decay of
      irradiation in the first order approximation on bleaching rate was obtained. The
      accuracy of the analytical function was evaluated with exact numerical solution
      computed with finite differentiates method. The FRDP method was successfully
      applied to fluorescein solution in the glycerol/water mixture (80%) under various
      experimental settings using home-made experimental set-up. The FRDP approach
      demonstrated 25-30 fold enhancement in signal intensity over classical
      fluorescence recovery after photobleaching (FRAP) method at 3-5 fold increase in
      total irradiation. Among other advantages of the FRDP is the opportunity to
      perform measurements on varying time scales under constant size of the bleaching
      spot, including "safe" long time measurements. The potential extra advantage of
      FRDP method for analysis of complex diffusion in the biological system is
      discussed.

PMID- 17004133
TI  - The perceived advantages and disadvantages of presymptomatic testing for Machado
      Joseph disease: development of a new self-response inventory.
AB  - This study describes the construction of a self-response inventory to evaluate
      the perception of advantages and disadvantages of the Machado-Joseph disease
      presymptomatic testing, in 44 individuals at-risk for this disease. The results
      showed that the reliability of this inventory was satisfactory. Factor analysis
      revealed a bidimensional structure: perceived advantages (pros) and perceived
      disadvantages (cons) of presymptomatic testing. Social desirability was found
      unrelated to the total scores of our inventory. Additional correlation studies,
      with other scales, confirmed the convergent validity of the instrument. These
      results suggest adequate construct validity. This inventory thus seems to be a
      proper instrument to assess expectations involved in the decision-making process
      of Machado-Joseph disease presymptomatic testing.

PMID- 17004136
TI  - [Not Available].

PMID- 17004135
TI  - Percutaneous interventional therapy of persistent biliary fistulas.
AB  - BACKGROUND: Persistent biliary leakage is a challenging problem when conservative
      treatment methods fail. We present our experience with alternative percutaneous
      radiologic interventions to seal refractory biliary leaks. METHODS: From April
      1998 to December 2005, a retrospective analysis of 23 patients with biliary
      leakage revealed six patients who were unresponsive to drainage were treated with
      use of Histoacryl (n = 5), microcoils (n = 2), or covered stent (n = 2) alone or
      in various combinations. RESULTS: In all patients, the biliary leakage ceased
      following a single procedure. Distally migration of microcoils into the abscess
      cavity was observed in a one coiling procedure, which was clinically
      insignificant. In one patient treated with covered stent, in-stent restenosis was
      seen in the postprocedural second year, which required another intervention. No
      recurrence of fistula was noted in the follow-up period (ranging from 6 to 47
      months). CONCLUSIONS: Persistent biliary fistulas can be treated successfully by
      means of various percutaneous radiological interventions that can decrease the
      morbidity associated with prolonged external drainage and avert the need for
      surgery. We recommend superselective embolization, preferably with Histoacryl,
      for a safe and effective control of leakage. Although restenosis after stenting
      remains problematic, covered stents should be reserved as a feasible alternative
      for selected cases.

PMID- 17004137
TI  - [Not Available].

PMID- 17004138
TI  - [Not Available].

PMID- 17004139
TI  - [Not Available].

PMID- 17004140
TI  - [Not Available].

PMID- 17004141
TI  - [Not Available].

PMID- 17004142
TI  - [Not Available].

PMID- 17004143
TI  - [Not Available].

PMID- 17004144
TI  - [Not Available].

PMID- 17004145
TI  - [Not Available].

PMID- 17004146
TI  - [Not Available].

PMID- 17004147
TI  - [Not Available].

PMID- 17004148
TI  - [Not Available].

PMID- 17004150
TI  - [Not Available].

PMID- 17004149
TI  - [Not Available].

PMID- 17004151
TI  - [Not Available].

PMID- 17004152
TI  - [Not Available].

PMID- 17004153
TI  - [Not Available].

PMID- 17004155
TI  - [Not Available].

PMID- 17004154
TI  - [Not Available].

PMID- 17004156
TI  - [Not Available].

PMID- 17004157
TI  - [Not Available].

PMID- 17004158
TI  - [Not Available].

PMID- 17004159
TI  - [Not Available].

PMID- 17004160
TI  - [Not Available].

PMID- 17004161
TI  - [Not Available].

PMID- 17004162
TI  - [Not Available].

PMID- 17004163
TI  - [Not Available].

PMID- 17004164
TI  - [Not Available].

PMID- 17004165
TI  - [Not Available].

PMID- 17004166
TI  - [Not Available].

PMID- 17004168
TI  - [Depression and anxiety symptom severity in a group of children with epilepsy and
      related factors].
AB  - OBJECTIVE: The aim of this study was to assess the anxiety and depression symptom
      severity in a group of epileptic children and compare the results to healthy
      controls. Additionally, the frequency of psychiatric disorders in epileptic
      children was also assessed. METHOD: The study compared 30 children, ranging in
      age from 8 to 16 years with epileptic disorder who attended a children's
      neurology clinic, with healthy controls using the State-Trait Anxiety Inventory
      and Children's Depression Inventory scores and suicidal ideation. The MINI was
      administered to epileptic patients to determine the frequency of psychiatric
      disorders in this clinical group. RESULTS: State anxiety scores of the epilepsy
      group were significantly higher compared to controls. No significant differences
      were found between patients and controls in terms of trait anxiety and depression
      scores. In all 3 scales boys scored significantly higher than girls. No
      significant relationships were found between symptom severity, duration of
      epilepsy, age of seizure onset and depression and anxiety scores. Psychiatric
      assessments with the MINI identified psychiatric disorders in 26.7% of epileptic
      patients. Two epileptic patients reported past suicidal attempts however, only 2
      patients were receiving psychiatric treatment. CONCLUSION: Psychiatric disorders
      were frequently observed in the group of epileptic patients. Psychiatric
      disorders occurred more frequently in boys compared to girls in this group.
      Clinicians should be more aware of accompanying psychiatric symptoms in epileptic
      patients and take the necessary precautions in the early period of the illness in
      an effort to prevent future mental health problems.

PMID- 17004169
TI  - [Psychopathology in parents of children with school phobia].
AB  - OBJECTIVE: In children, what is referred to as school phobia is usually avoidant
      behavior secondary to separation anxiety. The purpose of this study was to
      examine the psychopathology in parents of children with school phobia. METHOD:
      The study compared 2 groups of parents: 1) parents of children with school phobia
      (n = 50); 2) parents of children free of any psychiatric diagnosis (n = 50).
      Parents were assessed with the Structured Clinical Interview for DSM-IV (SCID-I)
      to determine rates of overall psychopathology by a second clinician blind to the
      diagnostic status of their children, and they were also administered the Beck
      Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Liebowitz Social
      Anxiety Scale (LSAS) to determine the presence of anxiety and mood disorders.
      Children with school phobia (n = 25), aged 6-12 years, and an age-and gender
      matched control group (n= 25) were assessed based on the criteria of the DSM-IV.
      Parents completed the Child Behavior Checklist (CBCL) 4-18. RESULTS: All of the
      children with school phobia met the criteria for an anxiety disorder. Parental
      psychopathology was higher in parents of children with school phobia than in
      parents of normal children. BDI, BAI, and fear and anxiety subscale scores of the
      LSAS were significantly higher in the parents of school phobic children than in
      the control group parents. CONCLUSION: The high rates of psychopathology in
      parents of children with school phobia suggested that treatment of children
      diagnosed as anxiety disorder should include the treatment of parents as well.

PMID- 17004170
TI  - [Jealousy in close relationships: personal, relational and situational
      variables].
AB  - PURPOSE: In this study, the effects of personal, situational, and relational
      variables (such as age, gender, gender role orientation, duration of
      relationship, relational satisfaction, and physical attractiveness of the
      partner) on jealousy are investigated. METHODS: A sample of 454 individuals
      currently involved in dating or marital relationships (48 % married, 52 %
      unmarried) completed the Romantic Jealousy Questionnaire, Bem Sex Role Inventory,
      and Rosenberg Self-Esteem Scale. Stepwise regression analyses and 2 (gender) x2
      (gender role orientation) x2 (relational type) ANOVA's were submitted for
      analyzing the data. RESULTS: Analysis indicated that unmarried people reported
      higher levels of jealousy than married people (F1-446 = 5.029). Married women
      reported less jealousy than unmarried women and married women reported more
      jealousy than married men. Age, relational satisfaction level, expectation level
      about the duration of the relationship, and physical attractiveness of the
      partner were unique predictors of the reported level of jealousy (R2 = 0.12;
      adjusted R2 = 0.11; P < 0.05). Women reported that they have more physical,
      emotional, and cognitive responses to jealousy compared to men. Women used more
      constructive (F1-446 = 6.27) and less destructive strategies than men (F1-446 =
      6.27). Unmarried people used more destructive strategies than married people (F1
      446 = 3.84). Age, self-esteem, and the duration of the relationship were unique
      predictors of coping strategies. CONCLUSION: The present study revealed that
      jealousy was a multidimensional variable. In particular, relational type, self
      esteem, age, relational satisfaction, and sex are highly correlated with
      jealousy.

PMID- 17004171
TI  - [Family centered evaluation of treatment outcome in schizophrenia: Marmara Family
      Interview for the Assesment of Psychiatric Treatment].
AB  - OBJECTIVE: Assessment of psychiatric treatment has been a central issue in
      psychiatric research. Most assessment tools are based on the patient's account
      and mainly focus on clinical agendas. Assessment tools, which gather the
      perspective of attached daily needs are limited. The purpose of our study was to
      evaluate the inter-rater reliability and internal consistency of the Marmara
      Family Interview for the Assessment of Psychiatric Treatment (MFIPT) in a
      clinical sample. METHOD: The study also aimed to explore a possible association
      between the investigated assessment tool and the Brief Psychiatric Rating Scale.
      Thirty patients were followed over a period of 6 months. RESULTS: The inter-rater
      reliability for the interview subscales were self care/hygiene: kappa= 0.77;
      social participation: kappa= 0.84; boundaries in daily life: kappa= 0.76;
      academic/work activities: r= 0.81, clinical condition/symptom severity: kappa=
      0.72; attitude towards treatment: kappa=0.82; participation in family
      crisis/emotional support: kappa= 0.77; participation in daily routines/household
      activities: kappa= 0.63; use of psychiatric services: kappa= 0.62. Cronbach's
      alpha was found to be 0.90 for the overall internal consistency of the assessment
      tool. The strongest correlation between the Brief Psychiatric Rating Scale and
      Marmara Family Interview for the Assessment of Psychiatric Treatment was the
      depression subscale and the participation in family crisis/emotional support item
      (r= 0.151; P > 0.05). CONCLUSION: Marmara Family Interview for the Assessment of
      Psychiatric Treatment is a reliable instrument for the assessment of daily
      results of the treatment and daily functioning by the caregivers. Although, it
      has some limitations in assessing the clinical course.

PMID- 17004172
TI  - [1999 Marmara earthquakes: a review of epidemiologic findings and community
      mental health policies].
AB  - Disasters are one of the most important priorities of community mental health.
      The Marmara earthquakes of August 17 and November 12, 1999 powerfully
      demonstrated the negative impacts of disaster trauma. Despite some methodological
      differences, studies clearly indicate that mental health problems related to
      earthquakes in Turkey are very prevalent and long lasting. Post Traumatic Stress
      Disorder (PTSD) and Major Depression (MD) are the most prevalent disorders in
      studies that are population-based and those that target high-risk groups. In
      various population-based studies, the PTSD prevalence ranged between 8 % and 63 %
      and the prevalence of MD was between 11 % and 42 %. On the other hand, PTSD
      prevalence was 2.7 %-8.5 % and MD was 1 %- 4.5 % for at-risk populations, such as
      health professionals and rescue workers. These high rates show the importance and
      necessity of outreach studies. Additionally, the general population and some
      organizations and professionals have different requirements ranging from training
      to psychological support and treatment. These studies highlight the development
      of mental health services and policies. Turkey is situated in a disaster zone;
      thus, such knowledge and practices could help prepare the nation's population and
      national policy for future disasters. In this review, first, mental health
      effects of disasters and some epidemiological findings of the Marmara earthquakes
      are discussed in light of the literature, and then mental health approaches and
      policies for disasters are briefly evaluated.

PMID- 17004173
TI  - [The correlates of healthcare seeking behavior in obsessive-compulsive disorder:
      a multidimensional approach].
AB  - Obsessive-compulsive disorder (OCD) is a chronic, distressing, and disabling
      illness that influences the family, academic, occupational, and social
      functioning of patients. One of the 10 leading causes of disability worldwide is
      OCD; however, despite the considerable distress and disability associated with
      the disorder and the availability of treatment options, many OCD sufferers
      usually are not inclined to seek healthcare. The factors that may be central to
      healthcare seek behavior in OCD has scarcely been described in the literature. It
      has been thought that the best predictor of healthcare seeking is severity of
      illness; however, individuals with OCD may have various barriers to seeking
      healthcare. Although non-disease and disease-related factors that may influence
      health care seeking are related in complex ways through reciprocal influences and
      feedback, each factor might be an independent predictor of use of healthcare
      services. This review aims to discuss the impact of the disease and general
      factors that impact healthcare seeking behavior in OCD. In this way, new
      information might be provided for the identification of targets to enhance the
      use of mental health services among OCD sufferers in the community.

PMID- 17004174
TI  - [Communicative function of dreams in the therapeutic process].
AB  - Sleep is not a loss of consciousness, but an altered state of consciousness. What
      appears in the dream is preconscious and ready to move into consciousness. This
      material may be manifested also during free association. The difference between
      free association and REM dreaming is that the preconscious material is presented
      in response to internal and/or external stimuli in a more coherent form during
      free associations, whereas during a REM dream, the material of daily experiences
      and perceptions that are fragmented in the preconscious are recombined in a less
      coherent form. The material that cannot be easily expressed during free
      association in the wakeful state, due to inner or external inhibition, appear in
      dreams and thus, find an easier way of expression. The dreams of patients who
      have difficulty directly expressing their thoughts, feelings, and experiences
      serve as a useful means of communication during the initial stage of therapy and
      provide valuable analytic material to help the progress of the psychoanalytic
      treatment. This phenomenon is described with a case presentation. The very
      inhibited patient who could not openly express her life experiences, emotions,
      and conflicts found it easier to report her dreams at the beginning of the
      therapeutic process. Through the material presented from these dreams, it became
      possible to open the path to direct verbal communication, to work through her
      problems, and to monitor the progress of the therapeutic process.

PMID- 17004175
TI  - [One mutation = one phenotype?].

PMID- 17004176
TI  - [Artificial disturbances].

PMID- 17004177
TI  - [Benign prostatic hyperplasia--botulinum toxin A in BPH with small prostate
      volume].

PMID- 17004178
TI  - [Interstitial cystitis--pentosan polysulfate and heparin improve quality of life
      and symptoms].

PMID- 17004179
TI  - [International Consensus Panel--treatment strategies for superficial bladder
      cancer].

PMID- 17004180
TI  - [Drug therapy for benign prostatic syndrome (BPS)].
AB  - Alpha1-receptor blockers (alfuzosin, doxazosin, tamsulosin and terazosin), 5alpha
      reductase inhibitors (dutasteride and finasteride) and combinations thereof are
      used in the drug treatment of benign prostatic syndrome. As before, there is
      still no evidence supporting the use of plant extracts, the use of
      anticholinergic substances alone or in combination with other BPS drugs is
      currently under investigation and should not be attempted outside of clinical
      trials. For all drugs the placebo effect is considerable. Accordingly, deviations
      from the recommended doses are rapidly associated with an activity loss over that
      of placebo. alpha1-Receptor blockers show a rapid onset of action and are
      slightly superior to 5alpha-reductase inhibitors with regard to the relief of
      symptoms. All alpha1-receptor blockers are similarly effective at adequate doses,
      however, quantitative differences are seen in the side effect profiles. 5alpha
      reductase inhibitors also provide relief from BPS-associated symptoms with the
      relief being volume-dependent. Prostate volume-dependent complications of BPS
      (operation risk and risk of acute urine retention) can be reduced by 5alpha
      reductase inhibitors. Long-term drug studies have demonstrated the superiority of
      combination therapies over monotherapies with alpha1-receptor blockers and 5alpha
      reductase inhibitors in patients with a high risk for progression. This
      superiority is accompanied by a combination of the respective side-effect
      profiles and their absolute increase. Besides poorer tolerability, combination
      therapies also result in higher costs. Thus, it is important to decide at an
      early stage which patients are to be treated with drugs and which by surgery.

PMID- 17004181
TI  - [Gemcitabine and carboplatin chemotherapy in advanced transitional cell carcinoma
      in regard to patients with impaired renal function].
AB  - PURPOSE: The aim of this analysis is the evaluation of the activity and toxicity
      of gemcitabine and carboplatin in patients with advanced urothelial transitional
      carcinoma (TCC) with special regard to patients with impaired renal function.
      PATIENTS AND METHODS: 30 consecutive patients with metastatic TCC [mean age: 68
      (range: 47 - 82) years, median ECOG-PS:1] were treated with gemcitabine (1000
      mg/m (2) on days 1 and 8 of a 21-day schedule) and carboplatin (AUC 4.5 day 1).
      In 15 patients (considered as renal unfit) a creatinine clearance of less than 60
      mL/min (range: 31 - 59 mL/min) was seen. RESULTS: Concerning the survival rate,
      no significant difference noticed between the two subgroups of renal impaired
      patients and patients with normal renal function was detected (median 13 vs. 14
      months, p = 0.901). An overall response rate of 50 % was obtained. In 16.7 % and
      33.3 % of all cases a complete or a partial response was noted. Median time to
      progression was 5.34 months. The 1-year-survival rate has been calculated as 51.8
      %. There was no restriction of renal function under chemotherapy in any single
      patient. CONCLUSIONS: The chemotherapy combination of gemcitabine and carboplatin
      is definitely powerful for a first-line-therapy in patients with advanced TCC.
      Toxicity is well manageable. Due to the dosage for carboplatin by AUC an
      adaptation to the glomerular filtration rate is possible. Decreases of
      effectiveness in cases of impaired renal function were not detected. Patients
      with metastatic TCC should be entered onto well designed, randomised clinical
      trials with the gemcitabine/carboplatin combination to afford a tailored
      chemotherapy.

PMID- 17004182
TI  - [Postoperative polyuria after laparoscopic adrenalectomy for pheochromocytoma].
AB  - Disturbances of osmoregulation leading to polyuria are well known complications
      after operations in the sella region. In contrast, increased urinary output
      following adrenalectomy is rare. We report a case of postoperative polyuria after
      laparoscopic adrenalectomy for pheochromocytoma with urine output up to 15 l per
      day. Treatment included careful monitoring of the patient and intravenous and
      oral replacement of fluids and electrolytes. In our case a normalisation of the
      urine output was observed after few days. A further treatment with vasopressin
      was not undertaken as the osmolality at all times was in normal range.

PMID- 17004183
TI  - [Sacral nerve root cysts--a rare cause of bladder dysfunction. Case report and
      review of the literature].
AB  - INTRODUCTION: Asymptomatic cysts of the sacral nerve roots display a prevalence
      of 5 % and are occasionally demonstrated by MRI of the spine. Depending on their
      size and localization, arachnoid cysts may cause sacral or perineal pain,
      radicular sensomotory symptoms and neurogenic bladder and bowel dysfunction by
      compression of the nerve roots. CASE REPORT: We report on a case of a recently
      developed neurogenic bladder dysfunction. MRI of the spine demonstrated two
      large, liquor-filled cysts of 2.5 and 3 cm diameter, bilaterally localized at the
      nerve roots S2/3. Neurological and urological examinations confirmed the
      diagnosis of symptomatic nerve root cysts at the level S2/3, resulting in
      detrusor areflexia. A microsurgical excision of the cysts ameliorated the
      patient's pain symptoms. However, the detrusor areflexia did not improve.
      CONCLUSIONS: Tarlov cysts are predominantly regarded an asymptomatic incidental
      feature of CT and MRI scans of the spine. The case of our patient, as well as the
      so far published reports indicate, however, that a Tarlov cyst may cause a
      variety of neurological and urological symptoms. Nerve root cysts should be
      seriously considered and not excluded at an early stage, especially when
      coincident with persistent neurological and urological symptoms.

PMID- 17004184
TI  - [Penile skin necrosis after application of a ring and defect coverage by a skin
      mesh graft].
AB  - INTRODUCTION: Penile strangulations are rare and always need an individual
      emergency treatment. Functional impairment and loss of organ integrity are the
      most serious complications. CASE REPORT: A 43-year-old man came to our ambulance
      with a penile skin necrosis and a penile abscess. This was caused by a heating
      pipe that he had put on his penis six weeks ago. We first removed the pipe and
      performed a necrosectomy in a second step a skin mesh graft was applied. Six
      months later we observed a satisfactory cosmetic and good functional result.
      CONCLUSION: Even in serious penile injuries caused by strangulation a penectomy
      can be avoided by means of an individually planned emergency treatment.

PMID- 17004185
TI  - [Retropubic adenomectomy without long-term catheter].

PMID- 17004186
TI  - [Rectal carcinoma: is too much neoadjuvant therapy performed? Proposals for a
      more selective MRI based indication].
AB  - The present-day optimised surgery (concept of total mesorectal excision) with
      quality assurance by standardized pathologic examination, advances in
      radiotherapy and the possibilities of high-spatial-resolution MR imaging require
      reconsideration of pros and contras of neoadjuvant therapy and respective data.
      According to the resulting new proposal neoadjuvant long-course radiochemotherapy
      is indicated for patients with 1) fixed questionably R0 resectable tumors, 2)
      mobile tumors with the MRT finding of tumor involving the mesorectal fascia or 1
      mm or less from it, 3) low rectal tumors extending below the levator origin and
      invading beyond the muscularis propria. If a high risk of local recurrence
      becomes apparent during surgery (tumor perforation, incision into or through
      tumor) or after pathologic examination (incomplete mesorectal excision, tumor 1
      mm or less from the circumferential resection margin) adjuvant radiochemotherapy
      is indicated. In case of lymph node metastasis postoperative chemotherapy is
      given.

PMID- 17004188
TI  - [Value of laparoscopic surgery in elective colorectal surgery with "fast-track"
      rehabilitation].
AB  - INTRODUCTION: Laparoscopic (LAP) versus open (CON) colonic resection with
      traditional perioperative care has some short term benefits postoperatively
      regarding functional recovery. Whether these benefits may also occur when all
      patients are treated with multimodal "fast-track"-rehabilitation programs is
      questionable. METHODS: Patients undergoing elective left sided colonic surgery
      were prospectively non randomised observed. The "fast-track" program included
      patient information, thoracic peridural analgesia, forced mobilisation and oral
      intake, and stress reduction. Endpoints were duration of postoperative ileus and
      hospital stay, general- and local complication, and pulmonary function. RESULTS:
      147 consecutive patients were operated on, 47 open and 100 laparoscopically. The
      time until oral intake was completed seemed to be shorter in the LAP-group
      (p=0.07) followed by a shorter hospital stay (p<0.01). The pulmonary function was
      postoperatively improved in the LAP-group compared to the CON-group (p<0,01).
      General complications (LAP 9% vs. CON 17%) were non significantly increased in
      the CON-group. Local complications increased in the CON-group (LAP 13% vs. CON
      28%, p<0,05). CONCLUSION: Even with perioperative "fast-track"-rehabilitation
      programs short term advantages were found in laparoscopic compared with open
      colonic surgery in a non randomised population. The clinical relevance should be
      examined in controlled randomised trials.

PMID- 17004187
TI  - [Clinical pathway (workflow) for diagnostic, therapy and follow-up in patients
      with rectal cancer].

PMID- 17004189
TI  - [25 years experience with the anastomotic stoma].
AB  - The anastomotic stoma is used since more than 25 years in emergency surgery of
      the bowel. To avoid a high risk primary anastomosis or a second laparotomy for
      reconstruction of the continuity, this procedure is performed, if sufficient
      bowel loop mobilization is possible. After resection of the diseased bowel
      segment, the proximal and distal loop are brought together and the posterior wall
      is then anastomized. The anterior wall of the anastomosis remains open and is
      fixed to the abdominal wall as a stoma. So far we have used this method in 136
      patients. In 117 cases this technique was performed during emergency operations.
      No patient died as a result of complications of the method; 48 patients, however
      died due to the primary disease. Bowel continuity could be restored in 100 cases.
      The anastomotic stoma protects the posterior wall from elevated pressure and
      allows daily control of the anastomosis. In the case of extraperitoneal closure,
      a secondary laparotomy for reconstruction of the continuity is not necessary. The
      anastomotic stoma can be performed in most regions of the small and large bowel.

PMID- 17004191
TI  - [Efficacy of treatment with Repithel and Jelonet in comparison to treatment with
      Jelonet alone - a randomized clinical trial in patients receiving meshed skin
      grafts].
AB  - Moist wound treatment is a well recognized method for the treatment of aseptic
      acute and chronic wounds. While the moist environment is beneficial to the
      woundhealing process, it also increases the risk of bacterial superinfection. We
      here report on the results of a clinical phase-III-study in which we tested the
      effect of a new PVP-iodine liposomal hydrogel (Repithel) on split-thickness skin
      grafts. This formulation optimizes moist wound treatment by improving the cell
      proliferation rate while preventing wound infection. AIM: The aim of this phase
      III-study was to analyse the efficacy and tolerance of Repithel in patients
      receiving meshed skin grafts. METHODS: 167 patients with transplantation wounds
      were either treated with lipid gauze alone (control group) or with lipid gauze
      and Repithel. In both groups the extent of neoepithelization, the frequency and
      severity of graft losses and the time until complete wound closure was achieved
      were determined. Analysis of the re-epithelization was achieved by
      photoplanimetry. Impedance measurements gave additional information on the
      regeneration of the epidermal barrier. RESULTS: Wounds receiving Repithel showed
      a significantly faster neoepithelisation than wounds which were treated with
      lipid gauze alone. Treatment with Repithel significantly reduced both the number
      of graft losses and the size of area lost. The time until wounds were closed
      completely was significantly shorter in patients receiving Repithel than in
      controls. The positive effects of Repithel on wound healing were especially
      observed in smokers, patients with chronic wounds, burns or infected wounds.
      CONCLUSIONS: Repithel supports healing of meshgraft transplants and reduces the
      risk of graft loss. Patients who heal poorly benefit particularly from the
      Repithel treatment.

PMID- 17004190
TI  - [Laparoscopic pancreatic resection].
AB  - Over a long time laparascopy for pancreatic diseases was performed only as
      staging laparoscopy in order to find hidden metastasis. The laparoscopic pyloric
      preserving duodeno-pancreatectomy showed many problems and could not establish.
      Laparoscopic distal resection of pancreas is much more feasible due to lack of
      intestinal anastomoses. Anyway there is only few literature about laparoscopic
      left pancreatic resection found. We demonstrate our experiences in four cases of
      the last months. RESULTS: In all four cases laparoscopic distal pancreatic
      resection was performed for tumor. In three cases the resection of the spleen was
      necessary. In another case we performed a laparoscopic hemifundoplicaton (DOR)
      for GERD in the same session. Histologic examination showed a neuroendocrine
      carcinoma, a serous-microcystic adenoma, a low differentiated ductal
      adenocarcinoma and an intraductal papillary-mucinous tumor of borderline type.
      Postoperative stay was between eight and ten days. There was no patient suffering
      from intra- or postoperative complications. CONCLUSION: Laparoscopic resection of
      distal pancreas shows the common benefit of minimal invasive surgery for the
      early postoperative period and is an attractive alternative for treatment of
      benign and semimalign pancreatic tumors.

PMID- 17004192
TI  - [Optimizing surgical hand disinfection].
AB  - For more than 110 years hands of surgeons have been treated before a surgical
      procedure in order to reduce the bacterial density. The kind and duration of
      treatment, however, has changed significantly over time. Recent scientific
      evidence suggests a few changes with the aim to optimize both the efficacy and
      the dermal tolerance. Aim of this article is the presentation and discussion of
      new insights in surgical hand disinfection. A hand wash should be performed
      before the first disinfection of a day, ideally at least 10 min before the
      beginning of the disinfection as it has been shown that a 1 min hand wash
      significantly increases skin hydration for up to 10 min. The application time may
      be as short as 1.5 min depending on the type of hand rub. Hands and forearms
      should be kept wet with the hand rub for the recommended application time in any
      case. A specific rub-in procedure according to EN 12791 has been found to be
      suitable in order to avoid untreated skin areas. The alcohol-based hand rub
      should have a proven excellent dermal tolerance in order to ensure appropriate
      compliance. Considering these elements in clinical practice can have a
      significant impact to optimize the high quality of surgical hand disinfection for
      prevention of surgical site infections.

PMID- 17004193
TI  - [Who does organize the operation theatre? Legal basis of the organization of the
      operation room].

PMID- 17004194
TI  - [Risk management in the operation room. Results of a pilot project of
      interdisciplinary "incident reporting"].
AB  - BACKGROUND: Methods for error analysis are suitable to increase patients' safety
      as well as staff satisfaction and may avoid, in a sense of process control,
      financial damage to the hospital. The aim of the presented pilot study was to
      establish and evaluate an incident reporting system as a first step towards a new
      safety culture. METHODS: In June 2003 an incident reporting system was introduced
      in the central surgical suite, in which the surgical and anaesthesiologic
      departments took part as well medical and nursing staff. Besides conceiving a
      report form, a "board of confidence" was elected, kick-off meetings were held and
      a baseline study on the basis of industrial psychological knowledge was
      initialised. RESULTS: The process of creating confidence is arduous and depends
      elementarily on sincere cooperation of management staff, especially of the heads
      of the departments. The exclusive participation of only two medical departments
      led to conflicts. Therefore, after finishing the pilot study, the system was
      expanded to the whole surgical suite including all operating departments. In
      order to increase the motivation for the strictly voluntarily participation, the
      frequency of regular echoes to the staff was optimised. To achieve high
      acceptance in the whole staff, the board of confidence needs a clearly defined
      position within the system of quality management. CONCLUSIONS: For the first time
      in Germany an incident reporting system under participation of several medical
      departments has been installed. After finishing the pilot project, in future we
      will be able to evaluate changes caused by this system. Simultaneously an
      electronic database for reported adverse events and strategies to avoid them are
      being developed based on similar systems in aviation industry. In near future,
      the system will be of increasing importance likewise for inpatient units and non
      operative departments.

PMID- 17004195
TI  - [Management of the operation room in an university hospital].
AB  - The heart of any surgical department is the operation room area. Any disturbances
      in the daily routine will affect the work flow of the whole hospital. As an
      example the major complaints of a university surgical department regarding
      workflow and communication are outlined. To solve these problems a team "OR
      organization" was established, which started the work based on a new developed OR
      statute. Within a short period the contentment of the employees as well as the
      workflow improved. But as a matter of fact, even in the following years of
      central OR management there is still the need to further stabilize the system and
      carefully improve the controlling system.

PMID- 17004196
TI  - [Computer-assisted process simulation: a suitable instrument for process
      optimization in hospitals].
AB  - The increasing financial pressure on hospitals resulting from changes in the
      health system demands detailed knowledge about the cost and earnings situation in
      the hospital. An essential part of strategic controlling now entails establishing
      structured cost-unit accounting. This can then be used for example through
      process optimization to ascertain savings potential and rationalization measures.
      This paper illustrates a possibility of using computer-assisted process
      simulation to find ways for prozess optimization. The simulation has been based
      on the treatment process "operative procedure" of a clinical pathway "CABG"
      developed in our hospital. The starting points for simulation possible prozess
      optimization consisted in the elimination of existing waiting times, respectively
      the parallel organization of certain partial processes. The software used for the
      simulation was Coral iGrafix Process 2003. The results of 1000 simulation
      processes reveal a clear reduction in the whole lead-time for the patient, both
      in avoiding waiting times and also in parallel process organization. In contrast
      to the initial situation (triangular distribution), the overall duration of the
      treatment section can be described approximately with normal distribution and a
      clear cluster of minimum overall durations. Computer-assisted process simulation
      is a suitable instrument for revealing and establishing possibilities for process
      optimization in hospitals, and therefore makes a valuable contribution to
      strategic controlling.

PMID- 17004197
TI  - [Does internal quality control reduce mistakes and complications? A plea for
      structured surgical education and increased transparency in clinical day-to-day
      work].
AB  - Quality control in most surgical departments shows major deficiencies. Only 50%
      have daily conferences on the surgical indication, and morbidity and mortality
      conferences are held in less than 20% of the institutions. However, pre-, intra-
      and postoperative quality control may be able to reduce mistakes and
      complications. Among others, the possibilities to reduce perioperative morbidity
      and mortality include preoperatively an early evaluation of the patient in the
      outpatient-clinic, intraoperatively a structured and didactic teaching of the
      surgical trainee and postoperatively a morbidity and mortality conference. In
      particular the latter one may promote surgical training and may increase
      transparency of the perioperative results. The delicate nature of morbidity and
      mortality conferences can be overcome in an atmosphere of mutual respect and
      personal honesty.

PMID- 17004198
TI  - [Lecture disasters - and how to prevent them].
AB  - Presentations at medical conferences can sometimes confuse or compromise
      understanding of current topics. Although considerable time and financial costs
      may be taken to be present at such events, all too often one must go through
      inferior presentations that are poorly structured and do not contribute to one's
      understanding of the topic at hand. A good presentation is distinguishable by the
      clear intentions of the speaker to give a good lecture. The presenter has worked
      extensively with his topic and is familiar with the audience. The presentation
      has a clear structure and finishes with a take-home message. The speaker takes
      the listener from his previous level of knowledge to a new understanding. To do
      so, both voice and body language are used. The supporting slides are simple and
      direct, and not overloaded with information. The speech conforms exactly with the
      pre-determined time limit.

PMID- 17004199
TI  - Antibodies against superantigenic exotoxins produced by Staphylococcus aureus in
      sera from mothers and their infants' cord blood.
AB  - A novel neonatal disease and puerperal toxic shock syndrome (TSS) induced by a
      superantigen, TSS toxin-1 (TSST-1), has spread throughout Japan. It is important
      to investigate serum titers against exotoxins in new mothers and in their
      infants' cord blood. We investigated antitoxin antibodies against TSST-1,
      staphylococcal enterotoxin (SE) A (SEA), SEB, and SEC, including immunoglobulin G
      (IgG) subclass specificity by enzyme-linked immunosorbent assay, in sera from 221
      mothers and 97 cord blood samples. The rate of mothers with negative anti-TSST-1
      antibody titer was high (more than 40%). Although antitoxin antibody titers in
      the sera of cord blood were well correlated with those in the sera of the mothers
      for every toxin, the tendencies of antibody transmission differed between toxins.
      Anti-TSST-1 antibody consisted mainly of IgG1 and IgG4 subclasses. Anti-TSST-1
      IgG1- and IgG4-specific antibody titers in cord blood were well correlated with
      those in the sera of the mothers. The low frequency of pregnant women with
      positive anti-TSST-1 antibody titers could be one reason for the spread of TSS in
      Japan. Neonates whose mothers have positive IgG titers against TSST-1 should be
      protected because the antibody is composed of the subclasses transferred well
      through the placenta.

PMID- 17004200
TI  - Influence of maternal nicotine exposure on neonatal rat bone: protective effect
      of ascorbic acid.
AB  - Limited research in young adults and immature animals suggests a detrimental
      effect of tobacco on bone during growth. We aimed to determine the adverse
      effects of maternal nicotine exposure during pregnancy and lactation on neonatal
      rat bone development, and to determine a protective effect of ascorbic acid.
      Gravid rats were assigned into three groups: two experimental and one control
      (group I). In the first experimental group (group II), pregnant rats received 3
      mg/kg/d nicotine subcutaneously during pregnancy from 1 to 21 days of gestation
      and lactation (until postnatal day 21). The second experimental group (group III)
      received nicotine and ascorbic acid (1 mg/kg body mass/d). Whole body mineral
      density (BMD), content (BMC), and area (BA) were measured on postnatal day 21.
      Histopathologic and morphologic findings of the femur were obtained. Maternal
      nicotine exposure decreased the body weight of the rat at the birth and postnatal
      day 21. The values of BMD, BA, and BMC of the groups were similar to each other.
      Width of the epiphyseal plate and the hypertrophic zone were higher in group III
      but lower in group II than in group I. Number of apoptotic chondrocytes was
      significantly increased in group II. The length of femur was higher in group I
      but lower in group II than in group III. Maternal nicotine exposure during
      gestation and lactation resulted in decreased body weight and bone lengthening.
      Ascorbic acid supplementation was found to prevent the adverse effects of
      maternal nicotine exposure on the growth plate.

PMID- 17004201
TI  - [Pulmonary rehabilitation of patients following thoracic and upper abdominal
      surgery].
AB  - The incidence of pulmonary complications is high in patients undergoing thoracic
      and upper abdominal surgery. Such surgery requires that an incision be made into
      the patient's respiratory muscles. As a result, each respiration taken induces
      great pain, which makes patients breathe shallowly and prevents their taking deep
      breaths and coughing. This article takes a pathophysiological approach in
      examining the mechanisms involved in the development of pulmonary complications
      and critiques the effectiveness of rehabilitative interventions that are
      described in the published literature. Upper arm exercise is suggested as an
      effective and acceptable intervention to promote pulmonary rehabilitation for
      this group of patients.

PMID- 17004202
TI  - [Rehabilitation care for female urinary incontinence].
AB  - The prevalence rate for urinary incontinence (UI) in women is higher than that in
      men. Urinary incontinence is a condition that presents considerable psychosocial
      implications, physical discomfort, and economic burdens; all of which diminish
      patient quality of life. In this presentation, types of UI, conservative
      treatments for UI and their effectiveness, and the application of conservative
      treatments for UI in nursing practice are discussed. Based on their recognized
      advantages and potential cost savings to Taiwan's health system, conservative
      treatments should be widely implemented in Taiwan. Conservative treatments of UI
      cover three main categories, including lifestyle interventions, physical
      therapies, and scheduled voiding regimens. The positive effects of physical
      therapy on UI have been reported worldwide. Further clinical evidenced-based
      studies are needed to explore the effects of lifestyle interventions and
      scheduled voiding regimens on UI. The value of delivering conservative treatments
      for UI in Taiwan has already been well established. Patients showed symptom
      improvement after nurse clinic consultations in Hong Kong, with the second best
      rate identified at continence clinics. In the United Kingdom, the positive
      effects of nurse-led continence service have been demonstrated at the community
      level. In light of increasing numbers of nurses with experience and training in
      continence care, the implementation of continence nurse clinics and nurse-led
      continence services in Taiwan is now possible.

PMID- 17004203
TI  - [Assistive technology devices for the elderly at home].
AB  - Using assistive technology (AT) to help the elderly and disabled overcome
      disabilities and attain their rehabilitation, learning, working and living
      potentials represents the mainstream trend in well-developed countries. According
      to data from Taiwan's Ministry of the Interior, Taiwan's senior citizen
      population exceeds two million. Proper application of AT can help achieve in
      Taiwan the goal of aging in place. Assistive technology devices can be divided
      into five categories, including barrier free environment (home modification),
      daily living aids, mobility aids, seating and positioning devices, and sensory
      aids. As of 2005, there were 16 senior care centers in Taiwan funded and
      administered by the Department of Health, all of which maintain interdisciplinary
      teams--comprising specialists in rehabilitation medicine, occupational therapy,
      physical therapy, speech therapy, nursing, education, social work and engineering
      -that provide service directly to persons with special needs and cooperate with
      manufactures to develop new assistive devices. Services provided by these centers
      include evaluation, design, customization, adaptation, maintenance, repair,
      therapy, training and technical assistance related to AT devices. The government
      has a legal responsibility to provide senior citizens in need with appropriate AT
      services. Service users, their families and professionals may contact centers
      directly for consultation.

PMID- 17004204
TI  - [Ethical dilemmas in caring for patients with SARS].
AB  - This paper explored experiences caring for patients with severe acute respiratory
      syndrome (SARS), with a focus on the suffering between the "private" and
      "professional" selves, in order to describe the psychological impact and ethical
      practice of SARS events as related to nursing professionals. Eight small group
      interviews were conducted with a total of twenty-one nurses with experience
      caring for SARS patients. Group interviews were audio-taped and transcribed for
      analysis. Data, analyzed using the constant comparative method, revealed the
      following three ethical dilemmas: suffering in care giving, response to the
      calling, and distresses involved in decision making. In this study, the authors
      further addressed relationships between suffering and ethical practice, the
      calling and a nurse's professional responsibilities, and transcendence in
      intersubjectivity. The authors hope that the results of this study will lead to a
      new understanding of ethical practices nursing and help nurses develop reflected
      care that promotes personal and professional growth.

PMID- 17004205
TI  - [Family satisfaction with systematic nursing instructions in a pediatric
      emergency department].
AB  - This study aimed to evaluate satisfaction with systematic nursing instructions
      among family members of pediatric emergency patients and to determine the degree
      to which family members complied with instructions provided. All subjects
      recruited were from a single medical center. A structured questionnaire was used
      to collect data. Written systematic nursing instructions were given to patient
      family members, supplemented by verbal interpretation. Family members were then
      contacted by telephone at 24 and 72 hours, respectively, after emergency
      department (ED) discharge. Questionnaires were completed and mailed back to the
      hospital within 72 hours. The 362 valid responses returned out of 700
      questionnaires dispensed represented a response rate of 51.7%. Data were analyzed
      using descriptive statistics, t-test, one-way ANOVA and Scheffe's test. Main
      study findings included: (1) Family member satisfaction with systematic nursing
      instructions was 83.8%; (2) Families with higher educational levels had higher
      expectations in terms of health education and were less satisfied with
      instructions provided; and (3) 61.4% of participants reported symptom relief
      after following systematic nursing instructions and, as a result, did not need to
      return for further clinical help. Results demonstrate that systematic nursing
      instructions are effective in improving family satisfaction and compliance with
      nursing instructions. In addition, these instructions help reduce the rate of
      unplanned return visits to the pediatric ED.

PMID- 17004206
TI  - [ICU project to improve pressure ulcer healing rates].
AB  - Pressure ulcers represent a very common complication in elderly and patients
      receiving bedridden care. Inappropriate management of this condition can lead to
      delayed healing, serious infections and even mortality. The rate of healing for
      pressure ulcers in our department was 0% between January and June, 2003. We
      studied this situation and identified the following problems: (1) improper
      diagnoses; (2) failure to implement a pressure ulcer care protocol; (3) lack of
      proper instruments to reduce pressure; and (4) failure to care properly for skin
      following excretion. Nursing knowledge and practice were not updated with new
      concepts and methods related to clinical pressure ulcer care. To solve these
      problems and improve pressure ulcer care effectiveness, we organized a special
      unit in July of the same year, which proceeded to arrange lectures and
      promotional campaigns, published a standardized care protocol, designed water
      cushions, and established proper post-excretion care procedures. According to
      observed results, our department improved its pressure ulcer healing rate by
      41.2% within 6 months. This project improved skin care quality and reduced
      pressure ulcer complications. We recommend that findings and measures be promoted
      in clinical practice.

PMID- 17004207
TI  - [An experience promoting evidence-based nursing at a medical center in central
      Taiwan].
AB  - In the 21st Century, evidence-based nursing (EBN) may provide a mechanism by
      which nurses can manage the explosion in published information in the literature,
      introduce new techniques, effectively control healthcare costs, and increase
      attention on nursing quality and health outcomes. The objective of this paper is
      to share the experience implementing evidence-based nursing. We had applied
      strategies to implement evidence-based nursing care in our hospital since 2002.
      Over a more than three-year period (January 2002 to October 2005), we held 46
      basic course sessions (around 1,840 attendees) and 58 advanced course sessions
      (around 500 attendees). There are 445 clinical questions with answered reports,
      Most questions related to foley care, central vein care and peripheral
      intravenous injection. Our nursing department revised three guidelines on nursing
      care skills related to suction and foley and nasal-gastric feeding to meet local
      conditions. Based on our subjective experience, promotion and implementation of
      EBN is feasible and helpful to update knowledge and decrease variance in clinical
      nursing care. However, further outcome research is needed in the future in order
      to obtain more objective evidence.

PMID- 17004208
TI  - [Application of music therapy for managing agitated behavior in older people with
      dementia].
AB  - Older people with dementia may display negative emotions, memory problems, sleep
      disturbance, and agitated behavior. Among these symptoms, agitated behavior has
      been identified by families and nursing staff as the care problem that presents
      the greatest challenge. Several studies have found that music therapy reduced
      agitated behaviors in those with dementia and recommended use of music as an
      effective strategy in managing this behavioral problem. Music therapy represents
      a lower cost, effective care approach that nursing staff can easily learn and
      apply to those with dementia. Furthermore, reductions in agitated behavior in
      dementia patients that result from music therapy can also alleviate caregiver
      stress and burden of care, leading to improvements in the health and quality of
      life of both dementia patients and their caregivers. This paper aims to introduce
      the principles and application of music therapy in the management of agitated
      behavior in those with dementia.

PMID- 17004209
TI  - [Acupoint stimulation as a smoking cessation therapy].
AB  - The purpose of this article was to review the literature on the effectiveness of
      stopping smoking through acupoint stimulation. Topics of interest included
      traditional Chinese medicine theory, acupoints selected for use in smoking
      cessation therapies, and the effectiveness and outcomes of acupoint stimulation
      therapies targeting smoking cessation. It is hoped that this article provides
      valuable knowledge and information on an alternative smoking cessation approach
      to give medical professionals additional options when assisting patients to quit
      smoking.

PMID- 17004210
TI  - [A concept analysis of successful weaning from mechanical ventilation].
AB  - The process of being weaned from mechanical ventilation is a stressful transition
      for critically ill patients who are taken off ventilation assistance and regain
      spontaneous breathing. Degree of weaning success is being increasingly used as an
      outcome indicator in clinical practice and lay literature. However, "successful
      weaning" remains a largely undefined concept in nursing practice. Following the
      concept analysis framework of Walker and Avant (1995), any such analysis that
      targets development of an operational definition of successful weaning should
      focus on two distinct sets of indicators, namely objective physiological and
      subjective psychological. Listing defining attributes and developing a model case
      will accurately reflect underlying relationships between weaning concepts.

PMID- 17004211
TI  - [The nursing experience in helping an unmarried adolescence girl to care for her
      premature infant].
AB  - This case study describes the author's experience in helping an unmarried
      adolescent girl learn to take proper care of her premature infant. Primary data
      were collected by observing interactions as well as from face-to-face and
      telephone interviews. Roy's model, family structure and the APGAR family function
      assessment theory were used to analyze data. Major problems identified included:
      alteration of family function, potential risk of parent/infant attachment and
      insufficient knowledge on the part of the mother regarding childcare. During the
      course of this study, the author served in a variety of roles including
      caregiver, educator and support-giver to the adolescent mother as well as
      provided training on in-home use of the Kangaroo technique for premature births.
      Maintaining a non-judgmental attitude and providing encouragement to the
      adolescent mother were essential to the success of assistance efforts. The
      establishment of an adolescent obstetrics outpatient service with social work
      intervention, discharge services and home visits by community nurses may be
      necessary in order to achieve holistic care goals.

PMID- 17004212
TI  - [A study of the process by which a school-age child adapted to body image changes
      following open-heart surgery].
AB  - This case report attempts to explore the adaptive process of body image changes
      in school-age children suffering from congenital ventricular septal defect (VSD)
      following open-heart surgery. After establishing trust relationship, we applied
      atraumatic care, projective communication techniques, interviews, behavioral
      observation, storytelling and play in our interaction with that child. We found
      the child experienced "body image disturbance" after open-heart surgery and
      underwent a four stage adaptive process as follows: (1) Impact (questioning,
      perception of punishment for wrongdoing, loss, anger); (2) Retreat (denial,
      anxiety, withdrawal, escaping social contact, inferiority); (3) Acknowledgment
      (cognitive change, active participation, future-oriented concerns); and (4)
      Reconstruction (positive self-image, reconstructing body image). Nursing
      intervention provided the case with more opportunities for sensory feedback and
      positive reinforcement and also assisted the patient to adopt a positive view of
      the situation and then to reconstruct and realize the meaning of such surgery. We
      reinforced the social supporting system to promote self-confidence, self-esteem,
      and self-value. The child finally accepted the wounds resulting from the
      operation as a symbol of "bravery"; a breakthrough likely to help in the child's
      re-entrance to school and normalization of life. Study findings both enhanced
      pediatric nurse understanding of the adaptive process involved in body image
      change and provided knowledge essential to designing flexible-option nursing
      interventions tailored to meet the demands of different adaptation stages.
      Obviously, such a caring model designed to meet the differing needs of different
      body image changes has the potential to benefit of body image integration greatly
      and can provide the pediatric nursing framework in the future.

PMID- 17004213
TI  - [Nursing experience with reducing delirium in a hospitalized elderly patient].
AB  - This article describes an experience of providing nursing care to an eighty year
      old patient with urinary tract infection (UTI). The author cared for this patient
      in the role of clinical geriatric nurse specialist from May 11 to 23 in 2005.
      Through comprehensive assessment, careful review of medical records, contact with
      family and nursing home healthcare workers, it was determined that the patient's
      cognition and physical function declines were due to delirium resulting from the
      last time the patient had been hospitalized in the intensive care unit (ICU). In
      order to prevent incidents of delirium, three nursing goals were set: controlling
      infection, avoidance of delirium recurrence, and recovery of prior levels of
      physical function and self-care ability. Nursing interventions used included UTI
      control, tube and catheter removal as early as possible, control of environmental
      factors, and muscle strength and exercise training. After two weeks of care, the
      patient could take food orally and the nasogastric (NG) tube had been
      successfully removed. Physical function and self-care ability improved from
      "dependent" to "partial assistance". Although UTI was controlled, removal of the
      foley tube failed due to prostate hypertrophy. No delirious event occurred during
      hospitalization and cognitive functions improved. From this experience, early
      assessment and intervention should be conducted for high-risk elderly patients in
      order to prevent delirious events and declines in cognitive and physical
      functions. The author hopes this case report will prove a useful reference to
      nurses charged with caring for elderly patients at risk for delirium.

PMID- 17004214
TI  - Phylogenetic and growth form variation in the scaling of nitrogen and phosphorus
      in the seed plants.
AB  - Plant biomass and nutrient allocation explicitly links the evolved strategies of
      plant species to the material and energy cycles of ecosystems. Allocation of
      nitrogen (N) and phosphorus (P) is of particular interest because N and P play
      pivotal roles in many aspects of plant biology, and their availability frequently
      limits plant growth. Here we present a comparative scaling analysis of a global
      data compilation detailing the N and P contents of leaves, stems, roots, and
      reproductive structures of 1,287 species in 152 seed plant families. We find that
      P and N contents (as well as N : P) are generally highly correlated both within
      and across organs and that differences exist between woody and herbaceous taxa.
      Between plant organs, the quantitative form of the scaling relationship changes
      systematically, depending on whether the organs considered are primarily
      structural (i.e., stems, roots) or metabolically active (i.e., leaves,
      reproductive structures). While we find significant phylogenetic signals in the
      data, similar scaling relationships occur in independently evolving plant
      lineages, which implies that both the contingencies of evolutionary history and
      some degree of environmental convergence have led to a common set of rules that
      constrain the partitioning of nutrients among plant organs.

PMID- 17004215
TI  - Direct and indirect effects of environmental temperature on the evolution of
      reproductive strategies: an information-theoretic approach.
AB  - For ectotherms, environmental temperature affects the optimal size and number of
      offspring via multiple mechanisms. First, temperature influences the performance
      of offspring, which directly affects the optimal size of offspring. Second,
      temperature influences maternal body size, which indirectly affects the optimal
      size and/or number of offspring when larger females acquire more energetic
      resources or provide better parental care. Although traditional statistical
      approaches might distinguish the relative importance of these effects, an
      information-theoretic approach enables one to estimate effects more accurately by
      identifying the best evolutionary model in a set of candidate models. Here, we
      use the Akaike Information Criterion to calculate the likelihoods of seven path
      models, each derived from one or more optimality models of reproduction.
      Variation in reproductive traits among populations of lizards (Sceloporus
      undulatus) was used to quantify support for the models. Our results
      overwhelmingly supported a model based on an indirect effect of temperature that
      is mediated by maternal size. Path coefficients of this model were consistent
      with the hypotheses that, first, larger females can acquire more energy for
      reproduction and, second, the survival of offspring depends on both their size
      and their density. Our analyses exemplify how information theory can identify
      evolutionary hypotheses that merit experimental testing.

PMID- 17004216
TI  - Stress hormone is implicated in satellite-caller associations and sexual
      selection in the Great Plains toad.
AB  - The effects of androgens on male-typical traits suggest that variation among
      males in circulating levels can play a major role in sexual selection. We
      examined whether variation in vocal attractiveness is attributable to differences
      in androgen levels among Great Plains toads (Bufo cognatus). We found that
      noncalling "satellite" males practicing an alternative mating tactic were more
      likely to associate with males producing long calls. However, callers with
      satellites did not have higher androgen levels than callers without satellites.
      Rather, callers with satellites had significantly lower corticosterone (CORT)
      levels than callers without satellites. A CORT manipulation experiment suggested
      that differences in calls for males with and without satellites were related to
      differences in CORT levels. Furthermore, there was a negative correlation between
      CORT level and call duration within most nights of chorus activity. However, the
      correlation was weak for the pooled data (across all nights), suggesting that
      local environmental and/or social factors also affect call duration. Last, we
      show that females preferred broadcast calls of longer duration, characteristic of
      males with satellites and low CORT. These results imply that satellites optimize
      their reproductive success by associating with males producing long calls.
      However, this association should negatively affect the fitness of attractive
      callers.

PMID- 17004217
TI  - A phylogenetic analysis of sleep architecture in mammals: the integration of
      anatomy, physiology, and ecology.
AB  - Among mammalian species, the time spent in the two main "architectural" states of
      sleep--slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep--varies greatly.
      Previous comparative studies of sleep architecture found that larger mammals,
      those with bigger brains, and those with higher absolute basal metabolic rates
      (BMR) tended to engage in less SWS and REM sleep. Species experiencing a greater
      risk of predation also exhibited less SWS and REM sleep. In all cases, however,
      these studies lacked a formal phylogenetic and theoretical framework and used
      mainly correlational analyses. Using independent contrasts and an updated data
      set, we extended existing approaches with path analysis to examine the integrated
      influence of anatomy, physiology, and ecology on sleep architecture. Path model
      structure was determined by nonmutually exclusive hypotheses for the function of
      sleep. We found that species with higher relative BMRs engage in less SWS,
      whereas species with larger relative brain masses engage in more REM sleep. REM
      sleep was the only sleep variable strongly influenced by predation risk; mammals
      sleeping in riskier environments engage in less REM sleep. Overall, we found
      support for some hypotheses for the function of sleep, such as facilitating
      memory consolidation or learning, but not others, such as energy conservation.

PMID- 17004218
TI  - Consumers limit the abundance and dynamics of a perennial shrub with a seed bank.
AB  - For nearly 30 years, ecologists have argued that predators of seeds and seedlings
      seldom have population-level effects on plants with persistent seed banks and
      density-dependent seedling survival. We parameterized stage-based population
      models that incorporated density dependence and seed dormancy with data from a
      5.5-year experiment that quantified how granivorous mice and herbivorous voles
      influence bush lupine (Lupinus arboreus) demography. We asked how seed dormancy
      and density-dependent seedling survival mediate the impacts of these consumers in
      dune and grassland habitats. In dune habitat, mice reduced analytical lambda (the
      intrinsic rate of population growth) by 39%, the equilibrium number of
      aboveground plants by 90%, and the seed bank by 98%; voles had minimal effects.
      In adjacent grasslands, mice had minimal effects, but seedling herbivory by voles
      reduced analytical lambda by 15% and reduced both the equilibrium number of
      aboveground plants and dormant seeds by 63%. A bootstrap analysis demonstrated
      that these consumer effects were robust to parameter uncertainty. Our results
      demonstrate that the quantitative strengths of seed dormancy and density
      dependent seedling survival--not their mere existence--critically mediate
      consumer effects. This study suggests that plant population dynamics and
      distribution may be more strongly influenced by consumers of seeds and seedlings
      than is currently recognized.

PMID- 17004219
TI  - An integrated approach to identify spatiotemporal and individual-level
      determinants of animal home range size.
AB  - Animal home range use is a central focus of ecological research. However, how and
      why home range size varies between individuals is not well studied or understood
      for most species. We develop a hierarchical analytical approach--using
      generalized linear mixed-effects modeling of time series of home range sizes-
      that allows variance in home range size to be decomposed into components due to
      variation in temporal, spatial, and individual-level processes, also facilitating
      intra- and interspecific comparative analyses. We applied the approach to data
      from a roe deer population radiotracked in central Italy. Over multiple
      timescales, temporal variation is explained by photoperiod and climate and
      spatial variation by the distribution of habitat types and spatial variance in
      radiotracking error. Differences between individuals explained a substantial
      amount of variance in home range size, but only a relatively minor part was
      explained by the individual attributes of sex and age. We conclude that the
      choice of temporal scale at which data are collected and the definition of home
      range can significantly influence biological inference. We suggest that the
      appropriate choice of scale and definition requires a good understanding of the
      ecology and life history of the study species. Our findings contrast with several
      common assumptions about roe deer behavior.

PMID- 17004220
TI  - Gene flow in complex landscapes: testing multiple hypotheses with causal
      modeling.
AB  - Predicting population-level effects of landscape change depends on identifying
      factors that influence population connectivity in complex landscapes. However,
      most putative movement corridors and barriers have not been based on empirical
      data. In this study, we identify factors that influence connectivity by comparing
      patterns of genetic similarity among 146 black bears (Ursus americanus), sampled
      across a 3,000-km(2) study area in northern Idaho, with 110 landscape-resistance
      hypotheses. Genetic similarities were based on the pairwise percentage
      dissimilarity among all individuals based on nine microsatellite loci (average
      expected heterozygosity=0.79). Landscape-resistance hypotheses describe a range
      of potential relationships between movement cost and land cover, slope,
      elevation, roads, Euclidean distance, and a putative movement barrier. These
      hypotheses were divided into seven organizational models in which the influences
      of barriers, distance, and landscape features were statistically separated using
      partial Mantel tests. Only one of the competing organizational models was fully
      supported: patterns of genetic structure are primarily related to landscape
      gradients of land cover and elevation. The alternative landscape models,
      isolation by barriers and isolation by distance, are not supported. In this black
      bear population, gene flow is facilitated by contiguous forest cover at middle
      elevations.

PMID- 17004221
TI  - Pollen dispersal in spatially aggregated populations.
AB  - We perform a theoretical study of effective pollen dispersal within plant
      populations exhibiting intraspecific spatial aggregation. We simulate nonuniform
      distributions of individuals by means of a Poisson cluster process and use an
      individual-based spatially explicit model of pollen dispersal to assess the
      effects of different aggregation patterns on the effective pollen pool size
      (N(ep)) and the axial variance of pollen dispersal (sigma (p)). Results show
      clear interactions between clumping and both N(ep) and sigma (p), whose precise
      form and intensity depend on the relative spatial scale of aggregation to pollen
      dispersal range. If clump size is small relative to dispersal range, clumping
      results in lower N(ep) and sigma (p) than in randomly distributed populations.
      Interestingly, by contrast, aggregation may actually enlarge N(ep) and has
      minimum impact on sigma (p) if clump size is near or above the scale of
      dispersal. High intraclump to global density ratios enhance the sensitivity of
      both N(ep) and sigma (p) to clumping, while leptokurtic pollen dispersal
      generates sharper reductions of both N(ep) and sigma (p) for small clump sizes
      and stronger increments of N(ep) for larger clump sizes. Overall, our results
      indicate that isolation-by-distance models in plants should not ignore the
      effects of intraspecific spatial aggregation on effective dispersal.

PMID- 17004222
TI  - Thermodynamics constrains the evolution of insect population growth rates:
      "warmer is better".
AB  - Diverse biochemical and physiological adaptations enable different species of
      ectotherms to survive and reproduce in very different temperature regimes, but
      whether these adaptations fully compensate for the thermodynamically depressing
      effects of low temperature on rates of biological processes is debated. If such
      adaptations are fully compensatory, then temperature-dependent processes (e.g.,
      digestion rate, population growth rate) of cold-adapted species will match those
      of warm-adapted species when each is measured at its own optimal temperature.
      Here we show that cold-adapted insect species have much lower maximum rates of
      population growth than do warm-adapted species, even when we control for
      phylogenetic relatedness. This pattern also holds when we use a structural
      equation model to analyze alternative hypotheses that might otherwise explain
      this correlation. Thus, although physiological adaptations enable some insects to
      survive and reproduce at low temperatures, these adaptations do not overcome the
      "tyranny" of thermodynamics, at least for rates of population increase. Indeed,
      the sensitivity of population growth rates of insects to temperature is even
      greater than predicted by a recent thermodynamic model. Our findings suggest that
      adaptation to temperature inevitably alters the population dynamics of insects.
      This result has broad evolutionary and ecological consequences.

PMID- 17004223
TI  - Maternal condition and facultative sex ratios in populations with overlapping
      generations.
AB  - Facultative investment in offspring sex is related to maternal condition in many
      organisms. In mammals, empirical support for condition-dependent sex allocation
      is equivocal, and there is some doubt as to theoretical expectations. Much theory
      has been developed to make predictions for condition-dependent sex ratios in
      populations with discrete generations. However, the extension of these
      predictions to populations with overlapping generations (OLGs; e.g., mammals) has
      been limited, leaving doubt as to the specific prediction for maternal-condition
      dependent sex ratios in mammals. We develop a population genetics model that
      incorporates maternal effects on multiple offspring fitness components in a
      population with OLGs. Using a rare-gene and evolutionarily stable strategy
      approach, we demonstrate that sex ratio predictions of this model are identical
      to those for equivalent discrete generations models. We show that the predicted
      sex ratios depend on the sex-specific ratio of R(o) (offspring lifetime fitness)
      for offspring of good and poor mothers. This offspring lifetime fitness rule
      indicates that empirical research on conditional sex ratios should consider all
      three components of offspring R(o) (juvenile survival, adult life span, and
      fertility).

PMID- 17004224
TI  - Natural selection on Erysimum mediohispanicum flower shape: insights into the
      evolution of zygomorphy.
AB  - Paleontological and phylogenetic studies have shown that floral zygomorphy
      (bilateral symmetry) has evolved independently in several plant groups from
      actinomorphic (radially symmetric) ancestors as a consequence of strong selection
      exerted by specialized pollinators. Most studies focused on unraveling the
      developmental genetics of flower symmetry, but little is known about the adaptive
      significance of intraspecific flower shape variation under natural conditions. We
      provide the first evidence for natural selection favoring zygomorphy in a wild
      population of Erysimum mediohispanicum (Brassicaceae), a plant showing extensive
      continuous variation in flower shape, ranging from actinomorphic to zygomorphic
      flowers. By using geometric morphometric tools to describe flower shape, we
      demonstrate that plants bearing zygomorphic flowers received more pollinator
      visits and had the highest fitness, measured not only by the number of seeds
      produced per plant but also by the number of seeds surviving to the juvenile
      stage. This study provides strong evidence for the existence of significant
      fitness differences associated with floral shape variation in E. mediohispanicum,
      thus illuminating a pathway for the evolution of zygomorphy in natural
      populations.

PMID- 17004225
TI  - Selective predation on Utah prairie dogs.
AB  - Predation always affects demography and population dynamics, but removal of
      certain types of individuals is especially consequential. Predators strike
      quickly and commonly avoid areas with human observers, however, and thereby make
      it difficult to document patterns of predation under natural conditions. At a
      colony of marked Utah prairie dogs (Cynomys parvidens), a high frequency of
      predation in 2005 provided an unusual opportunity to examine susceptibility of
      five types of individuals to predation by red foxes (Vulpes vulpes) and northern
      goshawks (Accipiter gentilis). Juveniles were more vulnerable than adults to
      predation by northern goshawks. Adults at the edge of the colony were more
      vulnerable than central adults to predation by both red foxes and northern
      goshawks. Recent immigrants, who were not yet familiar with the best routes for
      escape, were more likely than longtime residents to be captured by northern
      goshawks. Adult males, preoccupied with finding, impregnating, and guarding
      estrous females during the 17-day mating season, were easy targets for red foxes
      and northern goshawks. Pregnant females, who could not run quickly, were
      especially prone to predation by red foxes.

PMID- 17004226
TI  - The way of the samurai snail.

PMID- 17004227
TI  - Larval ecology, geographic range, and species survivorship in Cretaceous
      mollusks: organismic versus species-level explanations.
AB  - The observation that geographic range size in Cretaceous mollusks is correlated
      with species survivorship and is heritable at the species level has figured
      repeatedly in discussions of species selection over the past two decades.
      However, some authors have suggested that the relationship between mode of larval
      development and geographic range supports the reduction of this example to
      selection on organismic properties. Our reanalysis of Jablonski's work on
      heritability at the species level finds that geographic range is significantly
      heritable (using a randomization test) in both bivalves and gastropods, even
      within a single larval mode. Further, generalized linear models show that
      geographic range size is more important than larval mode in predicting extinction
      probability in both gastropods and bivalves. These results reaffirm the role and
      heritability of geographic range as a species-level property that can promote
      species selection; the model-based approach applied here may help to
      operationalize "screening off " and related approaches to evaluating hierarchical
      explanations in evolution.

PMID- 17004228
TI  - Interactions between the parasite's previous and current environment mediate the
      outcome of parasite infection.
AB  - The study of parasite virulence has generally focused on the conditions under
      which virulence is expected to increase or decrease over time and how the
      interactions between hosts and their environments may mediate the outcome of
      infection. Recently, parasite traits such as transmission, offspring production,
      and development have also been shown to be influenced by environmental variation.
      What is unclear is how variation in the parasite's environment may impact
      virulence. Recent theory demonstrates that plasticity can promote the evolution
      of decreased virulence; thus, understanding whether the parasite's environment
      can mediate virulence can improve predictions regarding the outcome of parasite
      infection. Here, an obligate mosquito parasite was reared in hosts fed high or
      low levels of food. Parasite oocysts (offspring) produced in these two host
      environments were subsequently fed to uninfected hosts. Parasites originating
      from well-fed hosts were found to be more virulent to these subsequent hosts
      compared to parasites originating from poorly fed hosts. Additionally, this
      effect was apparent only when current hosts were food deprived. These results
      demonstrate that parasite virulence was mediated by a cross-generational effect
      of the environment and that the overall outcome of infection was modified by
      variation in both the parasite's and host's environments.

PMID- 17004229
TI  - Will sympatric speciation fail due to stochastic competitive exclusion?
AB  - Sympatric speciation requires coexistence of the newly formed species. If
      divergence proceeds by small mutational steps, the new species utilize almost the
      same resources initially, and full speciation may be impeded by competitive
      exclusion in stochastic environments. We investigate this primarily ecological
      problem of sympatric speciation by studying the population dynamics of a
      diverging asexual population in a fluctuating environment. Correlation between
      species responses to environmental fluctuation is assumed to decrease with
      distance in trait space. Rapidly declining correlation in combination with high
      environmental variability may delay full speciation or even render it impossible.
      Stochastic extinctions impeding speciation are most likely when correlation
      decays faster than competition, for example, when demographic stochasticity is
      strong or when divergence is not accompanied by niche separation, such as in
      speciation driven entirely by sexual selection. Our general theoretical results
      show an interesting connection between short-term ecological dynamics and long
      term, large-scale evolution.

PMID- 17004230
TI  - Autonomous contractile activity in the isolated rat bladder is modulated by a
      TRPV1 dependent mechanism.
AB  - AIMS: Resiniferatoxin (RTX), a vanilloid compound and agonist of the transient
      receptor potential channel 1 (TRPV1), is known for its beneficial effects on
      neurogenic detrusor overactivity. The mainstream rationale for its use is the
      desensitization of TRPV1 on sensory bladder afferents. However, recent findings
      showed that TRPV1 is present in other cell types in the bladder. To eliminate the
      effects of RTX on spinal and central neural circuits, we investigated autonomous
      contractility in normal and neurogenic rat bladders after treatment with RTX.
      METHODS: Female Wistar rats were made paraplegic at vertebral level T8-T9.
      Animals were intravesically pre-treated with vehicle (ethanol 5%) or RTX (100 nM)
      and sacrificed after 72 hr. Each bladder was excised and placed in a heated organ
      bath, where intravesical pressures were measured. Effects on contractile
      parameters of intravesical volume load, the non-selective muscarinic receptor
      agonist carbachol (CA) and electrical stimulation (ES) of nerves were studied in
      both groups. RESULTS: In RTX-treated normal bladders we found shorter
      contractions with higher amplitude than in control bladders (P < 0.05). In RTX
      treated neurogenic bladders the amplitude and duration of autonomous contractions
      were increased compared with controls (P < 0.05). Furthermore RTX induced an
      increased response to CA and to ES (P < 0.05). CONCLUSIONS: RTX significantly
      affected the properties of autonomous bladder contractile activity. This provides
      evidence for local effects of RTX on bladder contractile activity, which are not
      mediated by afferent neural pathways and which may contribute to the beneficial
      effects on detrusor overactivity. TRPV1 and TRPV1(+) cells seem to play an
      important role in (autonomous) bladder contractility.

PMID- 17004231
TI  - Development and validation of a sensitive quantification method for
      hematoporphyrin monomethyl ether in plasma using high-performance liquid
      chromatography with fluorescence detection.
AB  - A rapid, sensitive, precise and specific method for determination of
      hematoporphyrin monomethyl ether (HMME), a novel photodynamic therapy (PDT) drug,
      was developed and validated using high-performance liquid chromatography (HPLC)
      with fluorescence detection. HMME was isolated from the plasma by a single-step
      liquid-liquid extraction with ethyl acetate. The analyte and internal standard
      fluorescein were baseline separated on a Diamonsil C(18) analytical column (4.6 x
      150 mm, 5 microm) and analyzed using a fluorescence detector with the excitation
      and emission wavelengths set at 395 and 613 nm, respectively. The method was
      linear in the concentration range 0.025-5 microg/mL with a lower limit of
      quantitation (LLOQ) of 10 ng/mL. The inter- and intra-day accuracies and
      precisions were all within 10% and the mean recoveries of HMME and fluorescein
      were 95 +/- 3.7 and 90 +/- 2.3%, respectively. The analyte was stable during all
      sample storage, preparation and analysis periods. This method was successfully
      applied to a pharmacokinetic study after a single-dose intravenous administration
      of HMME (5 mg/kg) to beagle dogs. This method was reproducible and sensitive
      enough for the pharmacokinetic study of HMME. Based on the results of the
      pharmacokinetic study, we suggest that a rather long light-avoiding time is
      essential for patients under HMME therapy.

PMID- 17004232
TI  - Adenosine released by astrocytes contributes to hypoxia-induced modulation of
      synaptic transmission.
AB  - Astrocytes play a critical role in brain homeostasis controlling the local
      environment in normal as well as in pathological conditions, such as during
      hypoxic/ischemic insult. Since astrocytes have recently been identified as a
      source for a wide variety of gliotransmitters that modulate synaptic activity, we
      investigated whether the hypoxia-induced excitatory synaptic depression might be
      mediated by adenosine release from astrocytes. We used electrophysiological and
      Ca2+ imaging techniques in hippocampal slices and transgenic mice, in which ATP
      released from astrocytes is specifically impaired, as well as chemiluminescent
      and fluorescence photometric Ca2+ techniques in purified cultured astrocytes. In
      hippocampal slices, hypoxia induced a transient depression of excitatory synaptic
      transmission mediated by activation of presynaptic A1 adenosine receptors. The
      glia-specific metabolic inhibitor fluorocitrate (FC) was as effective as the A1
      adenosine receptor antagonist CPT in preventing the hypoxia-induced excitatory
      synaptic transmission reduction. Furthermore, FC abolished the extracellular
      adenosine concentration increase during hypoxia in astrocyte cultures. Several
      lines of evidence suggest that the increase of extracellular adenosine levels
      during hypoxia does not result from extracellular ATP or cAMP catabolism, and
      that astrocytes directly release adenosine in response to hypoxia. Adenosine
      release is negatively modulated by external or internal Ca2+ concentrations.
      Moreover, adenosine transport inhibitors did not modify the hypoxia-induced
      effects, suggesting that adenosine was not released by facilitated transport. We
      conclude that during hypoxia, astrocytes contribute to regulate the excitatory
      synaptic transmission through the release of adenosine, which acting on A1
      adenosine receptors reduces presynaptic transmitter release. Therefore, adenosine
      release from astrocytes serves as a protective mechanism by down regulating the
      synaptic activity level during demanding conditions such as transient hypoxia.

PMID- 17004234
TI  - Immunodeficiency mutation databases (IDbases).
AB  - Primary immunodeficiencies (IDs) are a heterogenic group of inherited disorders
      of the immune system. Immunodeficiency patients have increased susceptibility to
      recurrent and persistent, even life-threatening infections. Mutations in a large
      number of genes can cause defects in different cellular functions and lead to
      impaired immune response. To date, approximately 150 IDs and more than 100
      affected genes have been identified. ID-related genes are distributed throughout
      the genome, and diseases can be inherited in an X-linked, an autosomal recessive,
      or an autosomal dominant way. We have collected ID mutation data into locus
      specific patient-related mutation databases, IDbases
      (http://bioinf.uta.fi/IDbases). Mutations are described at DNA, mRNA, and protein
      levels with links to reference sequences and reference articles. The mutation
      data has been collated into entries along with some clinical information. IDbases
      offer an easy way, e.g., to find recently identified mutations, to reveal
      genotype-phenotype correlations, and to discover a specific mutation or to
      examine the most common mutations in a single immunodeficiency related gene. At
      the moment we have databases for 107 ID genes with 4,140 public patient entries.
      An exhaustive statistical analysis of mutation data from the IDbases was made.
      Missense and nonsense mutations are the most common mutation types, and the most
      common single substitution is a nonsense mutation from tryptophan to a stop
      codon. Arginine is the most mutated as well as the most abundant mutant amino
      acid.

PMID- 17004233
TI  - The putative use of alpha-1-acid glycoprotein as a non-invasive marker of
      fibrosis.
AB  - The acute phase response to injury or infection results in alterations in the
      expression of the plasma proteins produced by the liver. Many of these
      biomolecules are glycosylated with oligosaccharide chains covalently attached to
      the polypeptide backbone and the extent and composition of this glycosylation can
      be altered in a disease-dependent manner. Of particular interest is the
      observation that the acute phase glycoprotein, alpha-1-acid glycoprotein (AGP)
      has altered glycosylation in several physiological and pathological conditions.
      It is posited that changes induced in liver diseases may reflect disease severity
      and may therefore act as a non-invasive marker of fibrosis. This study has
      investigated the glycosylation of AGP in the plasma of people with varying
      degrees of cirrhosis and fibrosis. Hyperfucosylation was observed in all disease
      samples in comparison to normal plasma and was significantly increased in
      cirrhosis. Both sialic acid and N-acetylgalactosamine (GalNAc) were negatively
      associated with fibrosis. Two samples were found to express GalNAc, which as a
      constituent of the glycosylation of serum proteins is rare. In conclusion,
      fucose, sialic acid and other aspects of the glycosylation of AGP are influenced
      by the degree of fibrosis and as such may prove a valuable prognostic indicator
      of the development of cirrhosis.

PMID- 17004235
TI  - Familial association of anxiety sensitivity and psychopathology.
AB  - The purpose of this study was to examine the association between parental
      (biological mother and father) and adult-offspring anxiety sensitivity (AS), and
      to determine whether parental AS is related to psychopathology in offspring. We
      obtained offspring (N=174) self-ratings of anxiety, mood, and stress symptoms,
      and assigned psychiatric diagnoses using a semistructured clinical interview.
      Biological mothers, fathers, and offspring independently completed a self-report
      measure of AS. We hypothesized that (1) there would be a positive relation
      between parental and offspring AS, and (2) AS in parents would be positively
      associated with psychopathology in offspring. Results indicated that paternal
      (but not maternal) AS was associated with offspring AS and psychopathology.

PMID- 17004236
TI  - Performance monitoring and response inhibition in anxiety disorders with and
      without comorbid ADHD.
AB  - Anxiety disorder (ANX) is characterized by heightened arousal, psychosocial and
      academic difficulties, and comorbidity with other disorders, in particular,
      attention-deficit/hyperactivity disorder (ADHD). The heightened arousal
      contributes to cognitive impairment by adversely affecting executive control of
      cognition. The nature of the effect on executive control is poorly understood.
      Research in this area could inform intervention, diagnostic, and etiological
      research. Our objective was to characterize children with ANX on measures of
      executive functioning, while controlling for comorbid ADHD. We compared children
      ages 6-14 with ANX (N=21), ADHD (N=78), ANX+ADHD (N=38), and normal controls (NC;
      N=40) on the stop task, a measure of performance monitoring and response
      inhibition. No difference was observed between NC and ANX groups in performance
      monitoring. Compared to the NC group, the three clinical groups showed inhibition
      deficits, and both ADHD and ANX+ADHD groups monitored less after responses. ANX
      was not associated with performance monitoring or inhibition deficits once
      comorbid ADHD was considered. This emphasizes the importance of controlling for
      comorbid ADHD in studies of cognition and anxiety.

PMID- 17004237
TI  - Ruminative coping among patients with dysthymia before and after pharmacotherapy.
AB  - The pivotal role of rumination in relation to other coping strategies was
      assessed in chronically depressed (dysthymic disorder) individuals versus
      nondepressed controls. Individuals with dysthymia demonstrated elevated use of
      rumination and other emotion-focused strategies (emotional expression, emotional
      containment, self- and other-blame). Among patients with dysthymia, rumination
      was linked to this limited array of emotion-focused efforts and diminished use of
      cognitive disengagement, whereas among controls, rumination was correlated with a
      broad constellation of problem- and emotion-focused strategies. Following 12
      weeks of pharmacotherapy (sertraline), despite attenuation of depressed mood and
      reduced rumination, the limited relations between rumination and emotion-focused
      efforts persisted. Inflexibility in the ability to combine various coping efforts
      effectively may be characteristic of individuals with dysthymia, potentially
      increasing risk for recurrence.

PMID- 17004238
TI  - No apoptosis is induced in rat cortical neurons exposed to GSM phone fields.
AB  - The aim of this study was to investigate the radiofrequency (RF) electromagnetic
      fields (EMF) effects on neuronal apoptosis in vitro. Primary cultured neurons
      from cortices of embryonic Wistar rats were exposed to a 900-MHz global system
      for mobile communication (GSM) RF field for 24 h in a wire-patch cell. The
      average-specific absorption rate (SAR) used was 0.25 W/kg. Apoptosis rate was
      assessed immediately or 24 h after exposure using three methods: (i) DAPI
      staining; (ii) flow cytometry using double staining with TdT-mediated dUTP nick
      end labeling (TUNEL) and propidium iodide (PI); and (iii) measurement of caspase
      3 activity by fluorimetry. No statistically significant difference in the
      apoptosis rate was observed between controls and 24 h GSM-exposed neurons, either
      0 h or 24 h post-exposure. All three methods used to assess apoptosis were
      concordant. These results showed that, under the conditions of experiment used,
      GSM-exposure does not significantly increase the apoptosis rate in rat primary
      neuronal cultures. This work is in accordance with other studies performed on
      cell lines and, to our knowledge, is the first one performed on cultured cortical
      neurons.

PMID- 17004239
TI  - Electromagnetic fields produced by GSM cellular phones and heart rate
      variability.
AB  - In this study, 26 healthy young volunteers were submitted to 900 MHz (2 W) GSM
      cellular phone exposure and to sham exposure in separate sessions. The study was
      designed to assess cardiac regulatory mechanism in different autonomic nervous
      system (ANS) states during exposure to low-intensity EMF. Rest-to-stand protocol
      was applied to evaluate ANS in quiet condition (rest, vagal prevalence) and after
      a sympathetic activation (stand). The procedure is conducted twice in a double
      blind design: once with a genuine EMF exposure and once with a sham exposure (at
      least 24 h apart). During each session three-leads electrocardiograms were
      recorded and RR series extracted off-line. Time domain and frequency domain HRV
      parameters were calculated in every phase of the protocol and during different
      exposures. The analysis of the data show there was no statistically significant
      effect due to EMF exposure both on main (i.e., RR mean) and most of the other HRV
      parameters. A weak interaction between some HRV parameters (i.e., SDNN, TINN, and
      triangular index in time domain and LF power in frequency domain analysis) and RF
      exposure was observed and this effect seems to be gathered around the sympathetic
      response to stand.

PMID- 17004240
TI  - Changes in heart rate variability among RF plastic sealer operators.
AB  - In a previous study, we showed that operators of radiofrequency (RF) plastic
      sealers, RF operators (n = 35) had a lower heart rate during nighttime compared
      to a control group (n = 37). We have analyzed the heart rate variability (HRV) on
      the same group of people to better understand the possible underlying rhythm
      disturbances. We found a significantly increased total HRV and very low frequency
      (VLF) power during nighttime among the RF operators compared to a control group.
      Together with our previous finding of a significantly lower heart rate during
      nighttime among the RF operators compared to the controls, this finding indicates
      a relative increase in parasympathetic cardiac modulation in RF operators. This
      could in turn be due to an adaptation of the thermoregulatory system and the
      cardiac autonomic modulation to a long-term low-level thermal exposure in the RF
      operators.

PMID- 17004241
TI  - Mobile phone base station-emitted radiation does not induce phosphorylation of
      Hsp27.
AB  - An in vitro study focusing on the effects of low-level radiofrequency (RF) fields
      from mobile radio base stations employing the International Mobile
      Telecommunication 2000 (IMT-2000) cellular system was conducted to test the
      hypothesis that modulated RF fields act to induce phosphorylation and
      overexpression of heat shock protein hsp27. First, we evaluated the responses of
      human cells to microwave exposure at a specific absorption rate (SAR) of 80
      mW/kg, which corresponds to the limit of the average whole-body SAR for general
      public exposure defined as a basic restriction in the International Commission on
      Non-Ionizing Radiation Protection (ICNIRP) guidelines. Second, we investigated
      whether continuous wave (CW) and Wideband Code Division Multiple Access (W-CDMA)
      modulated signal RF fields at 2.1425 GHz induced activation or gene expression of
      hsp27 and other heat shock proteins (hsps). Human glioblastoma A172 cells were
      exposed to W-CDMA radiation at SARs of 80 and 800 mW/kg for 2-48 h, and CW
      radiation at 80 mW/kg for 24 h. Human IMR-90 fibroblasts from fetal lungs were
      exposed to W-CDMA at 80 and 800 mW/kg for 2 or 28 h, and CW at 80 mW/kg for 28 h.
      Under the RF field exposure conditions described above, no significant
      differences in the expression levels of phosphorylated hsp27 at serine 82
      (hsp27[pS82]) were observed between the test groups exposed to W-CDMA or CW
      signal and the sham-exposed negative controls, as evaluated immediately after the
      exposure periods by bead-based multiplex assays. Moreover, no noticeable
      differences in the gene expression of hsps were observed between the test groups
      and the negative controls by DNA Chip analysis. Our results confirm that exposure
      to low-level RF field up to 800 mW/kg does not induce phosphorylation of hsp27 or
      expression of hsp gene family.

PMID- 17004242
TI  - A literature review: the effects of magnetic field exposure on blood flow and
      blood vessels in the microvasculature.
AB  - The effect of magnetic field (MF) exposure on microcirculation and
      microvasculature is not clear or widely explored. In the limited body of data
      that exists, there are contradictions as to the effects of MFs on blood perfusion
      and pressure. Approximately half of the cited studies indicate a vasodilatory
      effect of MFs; the remaining half indicate that MFs could trigger either
      vasodilation or vasoconstriction depending on initial vessel tone. Few studies
      indicate that MFs cause a decrease in perfusion or no effect. There is a further
      lack of investigation into the cellular effects of MFs on microcirculation and
      microvasculature. The role of nitric oxide (NO) in mediating microcirculatory MF
      effects has been minimally explored and results are mixed, with four studies
      supporting an increase in NO activity, one supporting a biphasic effect, and five
      indicating no effect. MF effects on angiogenesis are also reported: seven studies
      supporting an increase and two a decrease. Possible reasons for these
      contradictions are explored. This review also considers the effects of magnetic
      resonance imaging (MRI) and anesthetics on microcirculation. Recommendations for
      future work include studies aimed at the cellular/mechanistic level, studies
      involving perfusion measurements both during and post-exposure, studies testing
      the effect of MFs on anesthetics, and investigation into the microcirculatory
      effects of MRI.

PMID- 17004244
TI  - Role of blood flow on RF exposure induced skin temperature elevations in rabbit
      ears.
AB  - In this in vivo study, we measured local temperature changes in rabbit pinnae,
      which were evoked by radiofrequency (RF) exposure for 20 min at localized SAR
      levels of 0 (sham exposure), 2.3, 10.0, and 34.3 W/kg over 1.0 g rabbit ear
      tissue. The effects of RF exposures on skin temperature were measured under
      normal blood flow and without blood flow in the ear. The results showed: (1)
      physiological blood flow clearly modified RF induced thermal elevation in the
      pinna as blood flow significantly suppressed temperature increases even at 34.3
      W/kg; (2) under normal blood flow conditions, exposures at 2.3 and 10.0 W/kg,
      approximating existing safety limits for the general public (2 W/kg) and
      occupational exposure (10 W/kg), did not induce significant temperature rises in
      the rabbit ear. However, 2.3 W/kg induced local skin temperature elevation under
      no blood flow conditions. Our results demonstrate that the physiological effects
      of blood flow should be considered when extrapolating modeling data to living
      animals, and particular caution is needed when interpreting the results of
      modeling studies that do not include blood flow.

PMID- 17004245
TI  - Affective response to 5 microT ELF magnetic field-induced physiological changes.
AB  - Research into effects of weak magnetic fields (MFs) at biologically relevant
      frequencies has produced ambiguous results. Although they do affect human
      physiology and behaviour, the direction of effects is inconsistent, with a range
      of complex and unrelated behaviours being susceptible. A possible explanation is
      that these effects, rather than being directly caused, are instead related to
      changes in affective state. A previous study showed that MFs altered the
      affective content of concurrent perceptions, but it was unclear whether the
      emotional response was direct or indirect. Here it is shown that exposure to a 0
      5 microT MF (DC-offset sinudsoidal wave form) within EEG alpha-band frequencies
      (8-12 Hz), results in a reported change in emotional state. This relates to a
      decrease global field power but lacks the frontal alpha-asymmetry that would
      physiologically indicate a directly induced emotional state, suggesting that
      participant experiences are due to an interpretation of the effects of MF
      exposure.

PMID- 17004246
TI  - Improved cardiac function in infarcted mice after treatment with pluripotent
      embryonic stem cells.
AB  - Because pluripotent embryonic stem cells (ESCs) are able to differentiate into
      any tissue, they are attractive agents for tissue regeneration. Although
      improvement of cardiac function has been observed after transplantation of
      pluripotent ESCs, the extent to which these effects reflect ESC-mediated
      remuscularization, revascularization, or paracrine mechanisms is unknown.
      Moreover, because ESCs may generate teratomas, the ability to predict the outcome
      of cellular differentiation, especially when transplanting pluripotent ESCs, is
      essential; conversely, a requirement to use predifferentiated ESCs would limit
      their application to highly characterized subsets that are available in limited
      numbers. In the experiments reported here, we transplanted low numbers of two
      murine ESC lines, respectively engineered to express a beta-galactosidase gene
      from either a constitutive (elongation factor) or a cardiac-specific (alpha
      myosin heavy chain) promoter, into infarcted mouse myocardium. Although ESC
      derived tumors formed within the pericardial space in 21% of injected hearts,
      lacZ histochemistry revealed that engraftment of ESC was restricted to the
      ischemic myocardium. Echocardiographic monitoring of ESC-injected hearts that did
      not form tumors revealed functional improvements by 4 weeks postinfarction,
      including significant increases in ejection fraction, circumferential fiber
      shortening velocity, and peak mitral blood flow velocity. These experiments
      indicate that the infarcted myocardial environment can support engraftment and
      cardiomyogenic differentiation of pluripotent ESCs, concomitant with partial
      functional recovery.

PMID- 17004247
TI  - Sex ratios of offspring of patients with breast cancer and other endocrine
      related cancers.

PMID- 17004248
TI  - Microemulsion cyclosporine with C2 monitoring and tacrolimus in liver
      transplantation with or without hepatitis C virus infection.

PMID- 17004249
TI  - Early immunosuppression withdrawal after living donor liver transplantation and
      donor stem cell infusion.
AB  - Long-term results of organ transplantation are still limited by serious side
      effects of immunosuppressive drugs. A major issue, therefore, is to elaborate
      novel therapeutic protocols allowing withdrawal or minimization of
      immunosuppressive therapy after transplantation. We report on 3 patients
      prospectively enrolled in an original protocol designed to promote graft
      acceptance in living donor liver transplantation, using posttransplant
      conditioning with high doses of antithymocyte globulin followed by injection of
      donor-derived stem cells. In 2 patients, early immunosuppression withdrawal was
      possible, without subsequent graft deterioration. In these 2 cases, in vitro
      studies showed indices of immunological tolerance as assessed by specific
      hyporesponsiveness to donor alloantigens in mixed lymphocytes culture. In the
      third patient, acute rejection rapidly occurred after discontinuation of
      immunosuppression, and minimal immunosuppression has to be maintained during long
      term follow-up. In this case, a clearly distinct immunoreactive profile was
      observed as compared to tolerant patients, as no specific modulation of the
      antidonor response was observed in vitro. Of note, no macrochimerism could be
      detected in any of the 3 patients during the follow-up. In conclusion, these
      clinical observations demonstrated that, despite the absence of macrochimerism,
      donor stem cells infusion combined with recipient conditioning may allow early
      immunosuppression withdrawal or minimization after liver transplantation.

PMID- 17004250
TI  - The role of TIPS for portal vein patency in liver transplant patients with portal
      vein thrombosis.
AB  - The purpose of this research was to study the efficacy and outcomes of
      transjugular intrahepatic shunt (TIPS) in end-stage liver disease (ESLD) patients
      with portal vein thrombosis (PVT) eligible for orthotopic liver transplant. Nine
      consecutive patients with PVT underwent TIPS as a nonemergent elective outpatient
      procedure. The primary indication for TIPS was to maintain portal vein patency
      for optimal surgical outcome. Eight patients underwent contrast enhanced computed
      tomography (CT) and 1 magnetic resonance imaging diagnosing PVT. Shunt creation
      was determined by available targets at the time of TIPS and by prior imaging.
      Patients were followed with portography, ultrasound, CT, or magnetic resonance
      imaging, and the luminal occlusion was estimated before and after TIPS. Primary
      endpoints were transplantation, removal from the transplant list, or death.
      Stabilization, improvement, or complete resolution of thrombosis was considered
      successful therapy. Failures included propagation of thrombosis or vessel
      occlusion, and poor surgical anatomy due to PVT. Of 9 patients with PVT, TIPS was
      successfully placed in all patients without complication or TIPS-related
      mortality. Eight of 9 patients (88.8%) had improvement at follow-up. One patient
      failed therapy and re-thrombosed. Two patients (22.2%) were transplanted without
      complication and had no PVT at the time of transplant. Eight of 9 patients were
      listed for transplant at the time of their TIPS. Eight of 9 PVTs were
      nonocclusive. Four of 9 patients (44%) had evidence of cavernous transformation.
      Two patients expired during follow-up 42 and 44 months after TIPS. Three patients
      remain on the transplant list. One patient has not been listed due to
      nonprogression of disease. One patient has been removed from the transplant list
      because of comorbid disease. In conclusion, TIPS is safe and effective in
      patients with PVT and ESLD requiring transplant. Patients can be successfully
      transplanted with optimal surgical anatomy.

PMID- 17004251
TI  - Role of locoregional therapy for hepatocellular carcinoma before liver
      transplantation: answer or myth?

PMID- 17004253
TI  - Single-center experience of 39 patients with preoperative portal vein thrombosis
      among 404 adult living donor liver transplantations.

PMID- 17004254
TI  - Molecular and clinical perspectives of polyomaviruses: emerging evidence of
      importance in non-kidney transplant populations.
AB  - JC virus (JCV), BK virus (BKV) and simian virus 40 (SV40) are deoxyribonucleic
      acid (DNA) viruses, members of the family Polyomaviridae. These viruses establish
      persistent infections, and reactivate from latency in their host under
      immunosuppression. During the last few years there has been recognition of the
      morbidity related to polyomaviruses, particularly BKV in kidney transplant
      recipients. More importantly, recent studies indicate the potential implication
      of JCV, BKV, and SV40 in renal dysfunction among nonrenal organ transplant
      patients. Polyomaviruses are tumor-inducing viruses and animal models have
      provided evidence of the oncogenicity of these pathogens. Although data are not
      conclusive, molecular studies suggest an association of BKV and SV40 with
      malignancies among solid organ transplant patients. As new and potent
      immunosuppressive agents are introduced into clinical practice, it is believed
      that the incidence of polyomavirus-related diseases in organ transplantation
      might increase. This review evaluates the biologic and epidemiologic features of
      these 3 viruses, the data regarding their infections in nonkidney organ
      transplant patients and describes future directions in the management and
      research of these opportunistic pathogens.

PMID- 17004255
TI  - Diagnosis and staging of hepatocellular carcinoma prior to transplantation:
      expertise or failure.

PMID- 17004256
TI  - Single center experience of 39 patients with preoperative portal vein thrombosis
      among 404 adult living donor liver transplantations.
AB  - Living donor liver transplantation (LDLT) for patients with portal vein
      thrombosis (PVT) involves technical difficulty. The aim of this research was to
      analyze their preoperative diagnosis of PVT, operative procedures, and
      postoperative courses of patients with preoperative PVT. Thirty-nine patients of
      404 adult patients (9.7%) undergoing LDLT in our hospital from 1996 June to 2004
      December had PVT at their transplantation. Twenty-nine patients had intractable
      ascites, 21 had gastrointestinal bleeding, and 18 had encephalopathy. The
      thrombus was located in the portal trunk in 23, in the portal trunk and superior
      mesenteric vein (SMV) in 7, and developed into the SMV and the splenic vein in 8.
      The occlusive grade was partial in 29, and complete in 10 patients. The thrombus
      was removed by a simple technique, and eversion and/or incision technique, or
      total removal of the portal vein (PV). The PV was reconstructed with the
      thrombectomized native PV, with an interposed vein graft, or porto-caval
      hemitransposition. Advanced PVT had a significant impact on blood loss and
      hospital mortality. Three out of 10 patients with residual PVT required
      radiological and/or surgical intervention after transplantation. In conclusion,
      thorough planning is essential for a successful LDLT outcome for patients with
      preexisting PVT.

PMID- 17004258
TI  - A worldwide database for living donor liver transplantation is long overdue.

PMID- 17004259
TI  - 12-month follow-up analysis of a multicenter, randomized, prospective trial in de
      novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2
      monitoring) and tacrolimus.
AB  - The LIS2T study was an open-label, multicenter study in which recipients of a
      primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME)
      (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or
      tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to
      compare efficacy and safety at 3 and 6 months and to evaluate patient status at
      12 months. All patients received steroids with or without azathioprine. At 12
      months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a
      functioning graft (P not significant). Efficacy was similar in deceased- and
      living-donor recipients. Significantly fewer hepatitis C-positive patients died
      or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus
      (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was
      similar in each group. Based on biopsies driven by clinical events, the mean time
      to histological diagnosis of hepatitis C virus recurrence was significantly
      longer with CsA-ME (100 +/- 50 days) than with tacrolimus (70 +/- 40 days) (P <
      0.05). Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with
      tacrolimus. More patients who were nondiabetic at baseline received
      antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P <
      0.01). Of patients who were diabetic at baseline, more tacrolimus-treated
      individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P =
      0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was
      similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood
      concentration at 2 hours postdose and tacrolimus in liver transplant patients is
      equivalent to 12 months, and renal function is similar. More patients required
      antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

PMID- 17004260
TI  - An analysis of the UNOS liver transplant registry: high serum alpha-fetoprotein
      does not justify an increase in MELD points for suspected hepatocellular
      carcinoma.
AB  - The current United Network for Organ Sharing (UNOS) criteria for liver
      transplantation gives priority to patients with elevated serum alpha-fetoprotein
      (AFP; > or = 500 ng/mL) in the absence of radiologic evidence of a hepatic mass.
      Reports have shown that an elevated serum AFP is a poor diagnostic indicator for
      hepatocellular carcinoma (HCC) in patients with cirrhosis. Our aim was to
      determine if an AFP level above 500 ng/mL, in the absence of a liver mass by
      imaging study, correlates with the presence of HCC. Using the UNOS database we
      identified all patients transplanted for HCC in the United States between
      February 2002 and October 2005 based on these criteria. The data collected
      included: patient demographics, clinical information, and pathological outcomes.
      The data was analyzed using a chi-squared t-test and confirmed by logistic
      regression modeling. A total of 22 patients received a cadaveric liver
      transplant, while 1 received a living donor transplant during the study period.
      HCC was confirmed posttransplantation in only 6 patients (26%). There was no
      difference in race, gender, etiology of liver disease, or AFP level between
      patients with and without HCC but a significant difference in age (59.8 yr for
      HCC patients vs. 51.3 yr for the non-HCC group; P = 0.01). In conclusion, the
      majority of the patients who received extra Model for End-Stage Liver Disease
      (MELD) points based on an elevated AFP did not have HCC. Older age was a
      significant predictor for the presence of HCC in patients with a serum AFP
      greater than 500 ng/mL. These results demonstrate the poor correlation of serum
      AFP with the presence of HCC in patients awaiting liver transplantation.

PMID- 17004261
TI  - Guillain-Barre syndrome triggered by influenza vaccination in a recipient of
      liver transplant on FK506.
AB  - Guillain-Barre syndrome (GBS) has been rarely reported after liver
      transplantation and generally has good outcome. We report a liver transplant
      patient on FK506 (tacrolimus) who developed GBS 6 months after liver
      transplantation. There was no evidence of liver rejection or active infection.
      Despite treatment with intravenous immunoglobulin, the patient expired. GBS
      occurred despite downregulation of T cells by FK506, suggesting that humoral
      dysfunction might be the predominant mechanism of GBS in this report.

PMID- 17004262
TI  - Transjugular intrahepatic portosystemic shunt for treatment of intractable
      colonic ischemia associated with portal hypertension: a bridge to liver
      transplantation.
AB  - A 64-year-old man with portal hypertension secondary to hepatic nodular
      transformation was awaiting liver transplantation when he presented with severe,
      unrelenting abdominal pain, fever, and hypotension. Computed tomographyrevealed
      pneumatosis within the cecum and ascending colon. Because of his advanced liver
      disease and the perceived high likelihood of a poor outcome after colonic
      resection, he was managed medically. He improved initially but had a lengthy
      hospital course notable for intractable intestinal ischemia and gastrointestinal
      bleeding. Magnetic resonance angiography demonstrated patent mesenteric, portal,
      and hepatic vessels. His blood pressure was typically 90/55 mm Hg (mean arterial
      pressure, 65-70 mm Hg) despite intravenous fluids and blood product replacement.
      The hypothesis developed that the patient's level of portal hypertension was
      sufficiently severe (in the face of his low mean systemic arterial pressure) to
      compromise perfusion of the colonic mucosa. Were this hypothesis correct, then
      portal decompression might enhance the blood pressure gradient across the bowel
      and improve mucosal perfusion. With this in mind, a transjugular intrahepatic
      portosystemic shunt (TIPS) was placed. There was reduction of the portal vein to
      inferior vena cava gradient from 29 mm Hg to 9 mm Hg and his abdominal pain and
      gastrointestinal bleeding ceased. His prompt and sustained improvement following
      TIPS shunt placement is consistent with the hypothesis that high portal pressure
      was flow limiting, thus contributing to persisting intestinal ischemia. This case
      represents the first report of use of a TIPS shunt to address colonic ischemia
      associated with portal hypertension.

PMID- 17004263
TI  - Expression of interleukin-1beta, cyclooxygenase-2, and prostaglandin E2 in a
      rotator cuff tear in rabbits.
AB  - We investigated the specific factors related to shoulder pain due to a rotator
      cuff tear using a model in rabbits. A rotator cuff tear was surgically created,
      and the expression of interleukin-1beta (IL-1beta), prostaglandin E2 (PGE2), and
      cyclooxygenase-2 (COX-2) was analyzed. In the supernatant of the tissue culture
      of the torn tendon, IL-1beta production was detected. The amount of IL-1beta was
      highest 1 day after injury, and then decreased gradually to 21 days. PGE2, the
      mediator of pain and the product of COX-2, was also detected in the supernatant
      of the tissue culture. The production of PGE2 significantly increased to 7 days
      after injury, and then decreased to 21 days. RT-PCR analysis confirmed the mRNA
      expression of IL-1beta and COX-2 in the torn tendon. Immunohistochemical study
      demonstrated that cells in the tendon stump were immunopositive for IL-1beta and
      COX-2. Furthermore, in the affected joint, articular chondrocytes in the remote
      area from the tear expressed COX-2 strongly. When the rotator cuff is torn, IL
      1beta is produced in the torn tendon, and stimulates the expression of COX-2 in
      not only the torn tendon but also in articular chondrocytes. The COX-2 then
      produces PGE2, which would mediate shoulder pain.

PMID- 17004264
TI  - Tolerance for organ recipients: a clash of paradigms.

PMID- 17004265
TI  - Donor quality of life before and after adult-to-adult right liver live donor
      liver transplantation.
AB  - Donor right hepatectomy for adult-to-adult live donor liver transplantation
      (ALDLT) is a major surgical operation for the benefit of the recipient.
      Justification of procedure mandates knowledge of the possible physical and
      psychological negative effects on the donor. We prospectively and longitudinally
      quantified donor quality of life using generic and condition-specific
      questionnaires up to 1 year. The generic questionnaires were the Karnofsky
      Performance Status scale and the Chinese (Hong Kong) version of the Medical
      Outcomes Study 36-Item Short-Form Survey, which measures 8 health concepts: 4
      physical components and 4 mental components. Within 1 year, 30 consecutive donors
      were included. These 11 male and 19 female donors (36.7% and 63.3%, respectively)
      had a median age of 35 years (range, 21-56 years). There was no donor mortality
      or major complications. Donor quality-of-life worsening was most significant in
      the first 3 postoperative months, particularly among the physical components. The
      physical and mental components returned to the previous levels in 6 to 12 months'
      time, though the Karnofsky performance scores were slightly lower at 1 year (P =
      0.011). Twenty-six (86.7%) donors declared that they would donate again if there
      were such a need and it were technically possible. It was noticed that older
      donors were more likely to express unwillingness to donate again. In conclusion,
      the temporary worsening of donor quality of life substantiates ALDLT as an
      acceptable treatment modality.

PMID- 17004266
TI  - The influence of CTLA-4 gene polymorphisms on liver transplant outcomes.

PMID- 17004267
TI  - Successful adult-to-adult living donor liver transplantation combined with a
      cadaveric split left lateral segment.

PMID- 17004268
TI  - Effects of knee simulator loading and alignment variability on predicted implant
      mechanics: a probabilistic study.
AB  - Inherent variability in total knee arthroplasty loading and alignment, present in
      vivo and in simulator testing, may ultimately influence polyethylene tibial
      insert wear and long-term performance. The effect of this variability was
      quantified on implant kinematics and contact mechanics during simulated gait
      loading conditions using semi-constrained and unconstrained fixed bearing,
      cruciate retaining implants. A probabilistic finite element model of the Stanmore
      knee wear simulator was utilized to estimate the envelope of anterior-posterior
      (AP) and internal-external (IE) position and contact pressure and to evaluate the
      variability in corresponding ranges of motion (ROM). Variability levels were
      represented by standard deviations of up to 10% of the maximum value for load
      inputs and 0.25 mm and 0.5 degrees for component alignment inputs. Model
      predictions compared well with experimental simulator results for the semi
      constrained implant, with predicted positional envelopes of up to 1.8 mm (AP) an
      3.4 degrees (IE) for the semi-constrained and up to 2.6 mm (AP) and 3.7 degrees
      (IE) for the unconstrained implant at the variability levels evaluated. ROM
      varied by up to 22%, while peak contact pressure variations averaged less than 2
      MPa for both designs. For each implant, loading variability was more influential
      during the swing phase of gait, while alignment variability affected kinematics
      more during stance. The relative rank of sensitivities showed differences between
      the two designs, providing insight into critical parameters affecting kinematics
      and contact characteristics.

PMID- 17004269
TI  - Patellofemoral kinematics during knee flexion-extension: an in vitro study.
AB  - The purpose of this work was to obtain kinematics data for the normal human
      patellofemoral joint in vitro. Eight fresh-frozen cadaver knees were used. The
      heads of the quadriceps were separated, and the knees mounted in a kinematics
      rig. The femoral axis was aligned with an electromagnetic transmitter. The six
      heads of the quadriceps, including vasti medialis and lateralis obliquus, were
      loaded via cables according to their physiological cross-sectional areas and
      orientations. Magnetic trackers were mounted on the patella and tibia. The knee
      was flexed-extended against the extending muscle action, and patellar tracking
      was measured in six degrees of freedom. As the knee flexed, the patella flexed by
      0.7 times the tibiofemoral flexion angle. It also translated medially 4 mm to
      engage the trochlear groove at 20 degrees knee flexion, then translated to 7 mm
      lateral by 90 degrees knee flexion. The patella tilted progressively to 7 degrees
      lateral by 90 degrees knee flexion, and patellar medial-lateral rotation was
      usually less than 3 degrees. This is believed to be the first set of patellar
      tracking data obtained in both flexion and extension motion while the patella was
      acted on by a full set of quadriceps muscle tensions acting in physiological
      directions. These data may be used in future studies of the effects of
      pathologies on patellar tracking.

PMID- 17004270
TI  - Progress in type II dehydroquinase inhibitors: from concept to practice.
AB  - Scientists are concerned by an ever-increasing rise in bacterial resistance to
      antibiotics, particularly in diseases such as malaria, toxoplasmosis,
      tuberculosis, and pneumonia, where the currently used therapies become
      progressively less efficient. It is therefore necessary to develop new, safe, and
      more efficient antibiotics. Recently, the existence of the shikimic acid pathway
      has been demonstrated in certain parasites such as the malaria parasite. These
      types of parasites cause more than a million casualties per year, and their
      effects are particularly strong in people with a compromised immune system such
      as HIV patients. In such cases it is possible that inhibitors of this pathway
      could be active against a large variety of microorganisms responsible for the
      more opportunistic infections in HIV patients. Interest in this pathway has
      resulted in the development of a wide variety of inhibitors for the enzymes
      involved. This review covers recent progress made in the development of
      inhibitors of the third enzyme of this pathway, i.e., the type II dehydroquinase.
      The X-ray crystal structures of several dehydroquinases (Streptomyces coelicolor,
      Mycobacterium tuberculosis, etc.) with an inhibitor bound in the active site have
      recently been solved. These complexes identified a number of key interactions
      involved in inhibitor binding and have shed light on several aspects of the
      catalytic mechanism. These crystal structures have also proven to be a useful
      tool for the design of potent and selective enzyme inhibitors, a feature that
      will also be discussed.

PMID- 17004271
TI  - High and compact formation of baculoviral polyhedrin-induced inclusion body by co
      expression of baculoviral FP25 in Escherichia coli.
AB  - Previously, we found that baculoviral polyhedrin (Polh) can successfully be used
      in Escherichia coli as a fusion partner for the expression of special foreign
      proteins as inclusion bodies, and the resulting, easily isolatable Polh-induced
      fusion inclusion bodies had almost the same characteristics as the native Polh.
      Here, we investigated the effects of co-expression of baculoviral FP25 protein on
      Polh-induced inclusion-body production in an E. coli expression system, as FP25
      is known to be involved specifically in polyhedra formation. Using several
      analytical tools, including SDS-PAGE, pronase proteolysis, solubilization under
      alkaline conditions, and electron microscopy, we found that co-expressed FP25 was
      associated with Polh-induced inclusion bodies and that its co-expression led to
      formation of compact inclusion bodies as well as high production levels. We
      confirmed that FP25 co-expression induced higher production levels of other
      heterologous protein, antimicrobial peptide Hal18, fused with aggregation-prone
      Polh. Therefore, co-expression of baculoviral FP25 can be promisingly used to
      increase the levels of baculoviral Polh-fused foreign proteins, especially
      harmful proteins, expressed as inclusion bodies in an E. coli expression system.

PMID- 17004272
TI  - Sulfidogenic fluidized-bed treatment of metal-containing wastewater at low and
      high temperatures.
AB  - The applicability of a fluidized-bed reactor (FBR)-based sulfate reducing
      bioprocess was investigated for the treatment of iron-containing (40-90 mg/L)
      acidic wastewater at low (8 degrees C) and high (65 degrees C) temperatures. The
      FBRs operated at low and high temperatures were inoculated with cultures of
      sulfate-reducing bacteria (SRB) originally enriched from arctic and hot mining
      environments, respectively. Ethanol was supplemented as carbon and electron
      source for SRB. At 8 degrees C, ethanol oxidation and sulfate reduction rates
      increased steadily and reached 320 and 265 mg/L.day, respectively, after 1 month
      of operation. After this point, the rates did not change significantly during 130
      days of operation. Despite the complete ethanol oxidation and iron precipitation,
      the average sulfate reduction efficiency was 35 +/- 4% between days 30 and 130
      due to the accumulation of acetate. At 65 degrees C, a rapid startup was observed
      as 99.9, 46, and 29% ethanol, sulfate, acetate removals, in respective order,
      were observed after 6 days. The feed pH was decreased gradually from its initial
      value of 6 to around 3.7 during 100 days of operation. The wastewater pH of 4.3
      4.4 was neutralized by the alkalinity produced in acetate oxidation and the
      average effluent pH was 7.8 +/- 0.8. As in the low temperature FBR, acetate
      accumulated. Hence, the oxidation of acetate is the rate-limiting step in the
      sulfidogenic ethanol oxidation by thermophilic and psychrotrophic SRB. The
      sulfate reduction rate is three times and acetate oxidation rate is four times
      higher at 65 degrees C than at 8 degrees C.

PMID- 17004273
TI  - Protein-free transfection of CHO host cells with an IgG-fusion protein: selection
      and characterization of stable high producers and comparison to conventionally
      transfected clones.
AB  - In order to improve the current techniques of cell cultivation in the absence of
      serum, we have developed a protein-free transfection protocol for CHO cells,
      based on the Nucleofector technology. After starting with a heterogeneous pool of
      primary transfectants which express the fusion protein EpoFc, we isolated single
      clones and compared them with parallel clones generated by lipofection in serum
      dependent cultivation. Our intensive characterization program was based on
      determination of specific productivity (q(p)) and analysis of genetic parameters.
      In two nucleofection experiments, transfection with 5 microg of DNA resulted in
      best productivities of the primary cell pools. After subcloning, the q(p) could
      be raised up to 27 pg x cells(-1) x day(-1). While the serum-dependent
      transfectants exhibited specific productivities up to 57 pg x cells(-1) x day(-1)
      in serum-dependent cultivation, a significant decrease that resulted in the range
      of q(p) of the protein-free transfectants was observed after switching to protein
      free conditions. Investigation of genetic parameters revealed higher mRNA levels
      and gene copy numbers (GCN) for the protein-free adapted serum-dependent
      transfectants. Therefore, we assume that problems during protein-free adaptation
      (PFA) lead to a less efficient translation machinery after serum deprivation. We
      describe the generation of stable-producing recombinant CHO clones by protein
      free transfection of a protein-free adapted host cell line, which reduces the
      risk of adverse clonal changes after PFA. The main advantage of this approach is
      the earlier predictability of clone behavior, which makes the generation of
      production clones by protein-free transfection, a viable and highly efficient
      strategy for recombinant cell line development.

PMID- 17004274
TI  - Regulation of transcription by synthetic DNA-bending agents.
AB  - Gene expression is regulated by a complex interplay between binding and the three
      dimensional arrangement of transcription factors with RNA polymerase and DNA.
      Previous studies have supported a direct role for DNA bending and conformation in
      gene expression, which suggests that agents that induce bends in DNA might be
      able to control gene expression. To test this hypothesis, we examined the effect
      of triple-helix-forming oligonucleotide (TFO) bending agents on the transcription
      of luciferase in an in vitro transcriptional/translational system. We find that
      transcription is regulated only by a TFO that induces a bend in the DNA. Related
      TFOs that do not induce bends in DNA have no effect on transcription. Reporter
      expression can be increased by as much as 80 % or decreased by as much as 50 %
      depending on the phasing of the upstream bend relative to the promoter. We
      interpret the results as follows: when the bend is positioned such that the
      upstream DNA is curved toward the RNA polymerase on the same DNA face,
      transcription is enhanced. When the upstream DNA is curved away, transcription is
      attenuated. These results support the hypothesis that DNA-bending agents might
      have the capability to regulate gene expression, thereby opening up a previously
      undervalued avenue in research on the artificial control of gene expression.

PMID- 17004275
TI  - Analysis of subunit interactions in the iterative type I polyketide synthase ATX
      from Aspergillus terreus.

PMID- 17004276
TI  - Artificial metalloenzymes for enantioselective catalysis: recent advances.

PMID- 17004277
TI  - Dynamic kinetic resolution of secondary alcohols combining enzyme-catalyzed
      transesterification and zeolite-catalyzed racemization.
AB  - Hydrophobic zeolite beta containing low concentrations of Zr or Al was found to
      be a good catalyst for the racemization of 1-phenylethanol. The formation of
      styrene as a side product could be minimized by reducing the metal concentration
      in the zeolite beta. Combined with an immobilized lipase from Candida antarctica,
      the dynamic kinetic resolution of 1-phenylethanol to the (R)-phenylethylester can
      be achieved with high yield and selectivity. The reaction was best conducted in
      toluene as solvent at 60 degrees C, with higher temperatures leading to a loss in
      the enantioselectivity of the formed ester. By using high-molecular-weight acyl
      transfer reagents, such as vinyl butyrate or vinyl octanoate, a high enantiomeric
      excess of the product esters of 92 and 98 %, respectively, could be achieved.
      This is attributed to a steric effect: the bulky ester is less able to enter the
      pore space of the zeolite catalyst where the active sites for racemization are
      localized. Close to 100 % conversion of the alcohol was achieved within 2 h. If
      the more common acyl donor, isopropenyl acetate, was used, the enantiomeric
      excess (ee) of the formed ester was only 67 %, and the reaction was considerably
      slower.

PMID- 17004278
TI  - General synthesis of extended fused oligothiophenes consisting of an even number
      of thiophene rings.
AB  - The intramolecular double cyclization of bis(3-bromo-2-thienyl)acetylenes though
      a lithium-halogen exchange reaction with tBuLi followed by treatment with
      elemental sulfur produces two thiophene-fused thieno[3,2-c](1,2-dithiin)s. The
      subsequent dechalcogenation from the 1,2-dithiins with copper nanopowder affords
      tetrathienoacenes. On the basis of this two-step procedure, a series of
      trialkylsilyl-terminated, fused oligothiophenes, including hexathienoacene (a six
      thiophene-fused system) and octathienoacene (an eight thiophene-fused system),
      were synthesized. In the UV/Vis absorption and fluorescence spectra of the fused
      oligothiophenes, the absorption and emission maxima shift to longer wavelengths,
      as the pi-conjugation length increases. Their maximum wavenumbers have linear
      relationships with the reciprocal number of thiophene rings consisting of the pi
      conjugated frameworks. In the cyclic voltammograms, all the compounds show
      reversible oxidation waves, the first oxidation potential of which shifts to less
      positive as the conjugation length increases. Among them, the octathienoacene
      also shows a reversible second oxidation process. Indeed, its chemical oxidation
      with an excess amount of NO(+)SbF(6) (-) produces the dication as a golden
      crystal. The crystal structures of the neutral octathienoacene and its dication
      were determined by X-ray crystallography. While in the neutral state, the
      octathienoacene has a benzenoid structure with a large bond alternation of about
      0.04 A, its dication has a quinoid structure in which two cationic charges are
      mainly localized on the terminal rings.

PMID- 17004279
TI  - Temperature effects on ion association and hydration in MgSO4 by dielectric
      spectroscopy.
AB  - A detailed investigation of aqueous solutions of magnesium sulfate has been made
      by dielectric relaxation spectroscopy (DRS) over a wide range of frequencies
      (0.2<or=nu/GHz<or=89), concentrations (0.02<or=m/mol kg(-1)<or=2.3) and
      temperatures (5<or=theta/ degrees C<or=65). Consistent with literature data from
      other techniques, the spectra show clear evidence at all temperatures for the
      simultaneous existence of double solvent-separated (2SIP), solvent-shared (SIP)
      and contact (CIP) ion pairs and a triple ion (TI), Mg(2)SO(4) (2+)(aq). Increased
      formation of CIPs and especially TIs occurs with increasing temperature. The
      overall standard ion-association constant, K(A) degrees , corresponding to the
      equilibrium: Mg(2+)(aq)+SO(4) (2) (-)(aq) <==> MgSO(4) (0)(aq) is in good
      agreement with literature data at lower temperatures but is overestimated at
      higher temperatures due to processing difficulties. Despite the limited precision
      of the spectra, analysis of the individual steps in the ion-association process
      is possible for the first time. The 2SIPs are formed with little disturbance to
      their hydration shells, the (partial) destruction of which appears to occur
      mostly during the formation of SIPs. Effective hydration numbers derived from the
      DRS spectra indicate that both Mg(2+) and SO(4) (2-) influence solvent water
      molecules beyond their first hydration spheres but that MgSO(4)(aq) is less
      strongly hydrated than the previously studied CuSO(4)(aq).

PMID- 17004280
TI  - Vapor-phase Beckmann rearrangement of oxime molecules over H-Faujasite zeolite.
AB  - The Beckmann rearrangement (BR) plays an important role in a variety of
      industries. The mechanism of this reaction rearrangement of oximes with different
      molecular sizes, specifically, the oximes of formaldehyde (H(2)C=NOH), Z
      acetaldehyde (CH(3)HC=NOH), E-acetaldehyde (CH(3)HC=NOH) and acetone
      (CH(3))(2)C=NOH, catalyzed by the Faujasite zeolite is investigated by both the
      quantum cluster and embedded cluster approaches at the B3LYP level of theory
      using the 6-31G (d,p) basis set. To enhance the energetic properties, single
      point calculations are undertaken at MP2/6-311G(d,p). The rearrangement step,
      using the bare cluster model, is the rate determining step of the entire reaction
      of these oxime molecules of which the energy barrier is between 50-70 kcal mol(
      1). The more accurate embedded cluster model, in which the effect of the zeolitic
      framework is included, yields as the rate determining step, the formaldehyde
      oxime reaction rearrangement with an energy barrier of 50.4 kcal mol(-1). With
      the inclusion of the methyl substitution at the carbon-end of formaldehyde oxime,
      the rate determining step of the reaction becomes the 1,2 H-shift step for Z
      acetaldehyde oxime (30.5 kcal mol(-1)) and acetone oxime (31.2 kcal mol(-1)),
      while, in the E-acetaldehyde oxime, the rate determining step is either the 1,2 H
      shift (26.2 kcal mol(-1)) or the rearrangement step (26.6 kcal mol(-1)). These
      results signify the important role that the effect of the zeolite framework plays
      in lowering the activation energy by stabilizing all of the ionic species in the
      process. It should, however, be noted that the sizeable turnover of a reaction
      catalyzed by the Bronsted acid site might be delayed by the quantitatively high
      desorption energy of the product and readsorption of the reactant at the active
      center.

PMID- 17004281
TI  - d-Band catalysis in electrochemistry.

PMID- 17004282
TI  - A new family of homoleptic Ir(III) complexes: tris-pyridyl azolate derivatives
      with dual phosphorescence.

PMID- 17004283
TI  - Solid-phase synthesis, characterization, and antibacterial activities of
      metallocene-peptide bioconjugates.
AB  - This work shows how the introduction of an organometallic group enhances and
      modifies the specificity of biologically active peptides. Ferrocene was chosen as
      an organometallic group because it has been shown to alter the pharmacodynamic
      profile of bioactive compounds. A comparison with the isosteric cobaltocenium
      group allows one to explore the influence of charge and redox potential on the
      biological activity of the conjugates. Arginine and tryptophan containing
      peptides H-WRWRWR-NH(2) and H-RWRWRW-NH(2) and the metallocene peptide
      bioconjugates [M]-C(O)-RWRWR-NH(2) and [M]-C(O)-WRWRW-NH(2), where
      [M]=[Co(Cp)(C(5)H(4))](+), [Fe(Cp)(C(5)H(4))] were prepared by solid-phase
      peptide synthesis (SPPS). They were purified by HPLC, characterized by ESIMS and
      NMR spectroscopy, and tested for antibacterial properties against Escherichia
      coli, Pseudomonas aeruginosa, and Staphylococcus aureus using the minimum
      inhibitory concentration (MIC) test. In most cases, no metal-specific activity
      could be observed. However, the conjugate [Fe(Cp)(C(5)H(4))-C(O)-WRWRW-NH(2)] 6
      was found to be particularly effective against the Gram-positive S. aureus. The
      activity of this metallocene-pentapeptide conjugate (7.1 microM) was even better
      than the 20 amino acid naturally occurring pilosulin 2, which was used as a
      positive control. Unlike all other compounds tested, which were most active
      against the Gram-negative E. coli strain, the ferrocene conjugate 6 was the only
      compound in this series that was most active against Gram-positive bacteria.
      Given the health concerns resulting from multidrug resistant S. aureus strains,
      the incorporation of metallocenes may provide a novel line of attack.

PMID- 17004284
TI  - Modulation of unconventional fluorescence of novel photochromic perimidine
      spirodimers.
AB  - Fluorescence modulation by a class of photochromic perimidine spirodimers, which
      exhibit a characteristic fluorescence associated with their photochromic
      reactions, has been described. Upon irradiation using 365 nm light, these non
      fluorescent spiro molecules undergo a thermally-reversible ring opening at their
      spiro junction resulting in the generation of strong fluorescence. The
      fluorescing species is distinctly different from both the stable ring-closed and
      the ring-opened compounds, though it appears to have been formed from and remains
      in equilibrium with the photochemically generated ring-opened form. While the
      fluorescing species possesses a narrow absorption band with its maximum centered
      at 500 nm, the ring-opened form exhibits a broad absorption across the visible
      region with two maxima centered at 410 and 650 nm, respectively. After initiating
      the photochromic reactions in these molecules using 365 nm light, purely
      photochemically-controlled fluorescence modulation can be carried out using two
      wavelengths in the visible region, that is, 500 and 700 nm, while the equilibrium
      concentration of the ring-opened form and the fluorescing species is controlled.
      Fluorescence modulation is attained also by controlling the ratio of the ring
      closed and ring-opened forms by photochemical ring-opening and thermal ring
      closing reactions. The study on the effect of substitution of these molecules
      suggests that by extending the conjugation of the perimidine core in the ring
      opened form the molecule is rendered non-fluorescent and hence it can be assumed
      that the perimidine core forms the fluorescing entity of the molecule.

PMID- 17004285
TI  - Synthesis of the first chiral bidendate bis(trifluoromethyl)phosphane ligand
      through stabilization of the bis(trifluoromethyl)phosphanide anion in the
      presence of acetone.
AB  - Lewis acid/Lewis base adduct formation of the P(CF3)2- ion and acetone leads to a
      reduced negative hyperconjugation and, therefore, limits the C--F bond
      activation. The resulting increased thermal stability of the P(CF3)2- ion in the
      presence of acetone allows selective substitutions and enables the synthesis of
      the first example of a chiral, bidentate bis(trifluoromethyl)phosphane ligand: a
      DIOP derivative, [(2,2-dimethyl-1,3-dioxolane-4,5
      diyl)bis(methylene)]bis(diphenylphosphane), in which the phenyl groups at the
      phosphorus atoms are replaced by strong electron-withdrawing trifluoromethyl
      groups. The resulting high electron-acceptor strength of the synthesized
      bidentate (CF3)2P ligand is demonstrated by a structural and vibrational study of
      the corresponding tetracarbonyl-molybdenum complex. The stabilization of the
      P(CF3)2- ion in the presence of acetone is based on the formation of a dynamic
      Lewis acid/Lewis base couple, (CF3)2PC(CH3)2O-. Although there is no
      spectroscopic evidence for the formation of the formulated alcoholate ion, the
      intermediate formation of (CF3)2PC(CH3)2O- could be proved through the reaction
      with (CF3)2PP(CF3)2, which yields the novel phosphane-phosphinite ligand
      (CF3)2PC(CH3)2OP(CF3)2. This ligand readily forms square-planar Pt(II) complexes
      upon treatment with solid PtCl2.

PMID- 17004286
TI  - Imaging by sensitized oxygenations of photochromic anthracene films: examination
      of effects that improve performance and reversibility.
AB  - The aliphatic anthracene compound 1 and the oligomeric anthracene 2 were
      synthesized. Thin films of 1 and 2 mixed with the sensitizers
      tetraphenylporphyrin (TPP) and methylene blue (MB) were irradiated with visible
      light in air. Upon formation of singlet oxygen, the anthracene units were
      converted quantitatively to the corresponding endoperoxides. Heating of the
      irradiated samples afforded the parent anthracenes with high yields. Here, we
      demonstrate that the kinetics and reversibility of this reaction strongly depend
      on the microenvironment of the anthracene groups in the two compounds. The
      photooxidation of thin films of 1 is accompanied by interesting changes in the
      morphology of the film and allows the first application of 1 as a nondestructive
      negative-tone photoresist for lithography and as an oxidizing ink. The morphology
      of 2 remained unchanged after photooxidation as a result of the stabilizing
      oligomer backbone. This stabilizing effect significantly improves the
      photochromic performance of 2. The reversibility of the photooxidation is very
      high (>90 %) for oligomeric films of 2 after several cycles of irradiation and
      heating. Decomposition of the anthracene and a loss of the activity of the
      sensitizer diminish slightly the performance of the monomeric species.

PMID- 17004287
TI  - Preparation of high-surface-area zinc oxide with ordered porosity, different pore
      sizes, and nanocrystalline walls.
AB  - Transition-metal-oxide materials possessing ordered mesoporosity have recently
      attracted significant research interest due to their numerous potential
      applications. Among them, ordered mesoporous zinc oxide (ZnO) is a very tempting
      material because of the importance of ZnO in heterogeneous catalysis. Here, first
      results of the preparation of ordered mesoporous ZnO materials by using different
      templates are reported. Porous materials with high surface area, different pore
      sizes, and nanocrystalline ZnO walls were obtained. Furthermore, we compare the
      two fundamental templating techniques, involving liquid crystals or ordered
      mesoporous carbon materials as templates. Regarding the formation of mesoporous
      ZnO, it was evident that the hard-matter carbon template is superior.

PMID- 17004288
TI  - Studies on Pd(0)-catalyzed cyclization of N-3,4-alkadienyl toluenesulfonamides
      with organic halides: selective synthesis of 2,3-dihydropyrroles, 1,2,3,6
      tetrahydropyrridines, and azetidines.
AB  - The palladium-catalyzed coupling-cyclization of beta-amino allenes with organic
      halides ranging from aryl halide to 1-alkenyl halide was studied. 2,3-Dihydro-1H
      pyrroles were obtained by reaction of 3-substituted-5-unsubstituted-3,4-allenyl
      amides under conditions A, while the reaction of 5-substituted-3,4-allenyl amides
      afforded 1,2,5,6-tetrahydropyridines and/or azetidines with high de under
      conditions B or C. The skeleton and relative configuration of the six-membered
      products were established by the X-ray diffraction studies of 10 ka. Allenyl
      amide 4 q reacted with 1,4-diiodobenzene 6 r to afford double cyclization product
      15. The structure of its major stereoisomer was also determined by the X-ray
      diffraction study.

PMID- 17004289
TI  - Photochemistry of peroxoborates: borate inhibition of the photodecomposition of
      hydrogen peroxide.
AB  - The UV absorbance and photochemical decomposition kinetics of hydrogen peroxide
      in borate/boric acid buffers were investigated as a function of pH, total
      peroxide concentration, and total boron concentration. At higher pH borate/boric
      acid inhibits the photodecomposition of hydrogen peroxide (molar absorptivity and
      quantum yield of H(2)O(2) and HO(2) (-), (19.0+/-0.3) M(-1) cm(-1) and 1, and
      (237+/-7) M(-1) cm(-1) and 0.8+/-0.1, respectively). The results are consistent
      with the equilibrium formation of the anions monoperoxoborate,
      K(BOOH)=[H(+)][HOOB(OH)(3) (-)]/([B(OH)(3)][H(2)O(2)]), 2.0 x 10(-8), R. Pizer,
      C. Tihal, Inorg. Chem. 1987, 26, 3639-3642, and monoperoxodiborate,
      K(BOOB)=[BOOB(2-)]/([B(OH)(4) (-)][HOOB(OH)(3) (-)]), 1.0+/-0.3 or 4.3+/-0.9,
      depending upon the conditions, with molar absorptivity, (19+/-1) M(-1) cm(-1) and
      (86+/-15) M(-1) cm(-1), respectively, and respective quantum yields, 1.1+/-0.1
      and 0.04+/-0.04. The low quantum yield of monoperoxodiborate is discussed in
      terms of the slower diffusion apart of incipient (.)OB(OH)(3) (-) radicals than
      may be possible for (.)OH radicals, or a possible oxygen-bridged cyclic structure
      of the monoperoxodiborate.

PMID- 17004290
TI  - Supported ionic-liquid films (SILF) as two-dimensional nanoreactors for
      enantioselective reactions: surface-mediated selectivity modulation (SMSM).
AB  - Supported ionic-liquid films (SILF) of nanometric thickness containing
      bis(oxazoline)-copper complexes can be used as recoverable catalysts for
      enantioselective cyclopropanation reactions. When a thin film of ionic liquid is
      supported on a clay, the system behaves as a nearly two-dimensional nanoreactor
      in which the restrictions in rotational mobility and the close proximity to the
      surface support produce variations in the stereo- and enantioselectivities,
      leading to a complete reversal of the overall selectivity of the reaction. As an
      example, the cyclopropanation of styrene changes from a preference for the
      (1S,2S)-trans isomer in bulk solution to the (1R,2S)-cis isomer in the SILF. This
      variation is strongly dependent on both the thickness of the film and the nature
      of the support. Only layered solids with negative charges in the layers (clays)
      give rise to this type of behaviour, showing that the formation of ion pairs may
      be a decisive factor. This unexpected effect also shows the existence of
      differences between bulk and supported ionic liquids.

PMID- 17004291
TI  - Water-soluble carbosilane dendrimers: synthesis biocompatibility and complexation
      with oligonucleotides; evaluation for medical applications.
AB  - Novel amine- or ammonium-terminated carbosilane dendrimers of type nG
      [Si{OCH2(C6H3)-3,5-(OCH2CH2NMe2)2}]x, nG-[Si{O(CH2)2N(Me)(CH2)2NMe2}]x and nG
      [Si{(CH2)3NH2}]x or nG-[Si{OCH2(C6H3)-3,5-(OCH2CH2NMe3 +I-)2}]x, nG
      [Si{O(CH2)2N(Me)(CH2)2NMe3 +I-}]x, and nG-[Si{(CH2)3NH3 +Cl-}]x have been
      synthesized and characterized up to the third generation by two strategies: 1)
      alcoholysis of Si--Cl bonds with amino alcohols and subsequent quaternization
      with MeI, and 2) hydrosilylation of allylamine with Si--H bonds of the dendritic
      systems and subsequent quaternization with HCl. Quaternized carbosilane
      dendrimers are soluble in water, although degradation is apparent due to
      hydrolysis of Si--O bonds. However, dendrimers containing Si--C bonds are water
      stable. The biocompatibility of the second-generation dendrimers in primary cell
      cultures of peripheral blood mononuclear cells (PBMCs) and erythrocytes have been
      analyzed, and they show good toxicity profiles over extended periods. In
      addition, we describe a study on the interactions between the different
      carbosilane dendrimers and DNA oligodeoxynucleotides (ODNs) and plasmids along
      with a comparative analysis of their toxicity. They can form complexes with DNA
      ODNs and plasmids at biocompatible doses via electrostatic interaction. Also a
      preliminary transfection assay has been accomplished. These results demonstrate
      that the new ammonium-terminated carbosilane dendrimers are good base molecules
      to be considered for biomedical applications.

PMID- 17004292
TI  - Efficient synthesis of chiral 1,1'-binaphthalenes by the asymmetric suzuki
      miyaura reaction: dramatic synthetic improvement by simple purification of
      naphthylboronic acids.
AB  - Naphthylboronic acids prepared as reported in the literature are contaminated
      with HCl. A very simple purification prior to their use in Suzuki-Miyaura
      couplings has been found to be crucial, rendering efficient some reactions that
      had been reported in the literature either to fail or to give extremely poor
      yields. With this improvement, parent boronic acids can be used instead of esters
      at moderate temperatures, and bromo derivatives can be used instead of iodo
      derivatives. Convenient access to chiral sterically hindered binaphthalene
      derivatives has been achieved through the use of boronic acids,
      bromonaphthalenes, and ferrocenylphosphane ligands. The products were obtained in
      good yields (95-55 %) and with good enantioselectivities (90-50 %). Bulkier
      ligands are less efficient in the coupling of hindered partners.

PMID- 17004293
TI  - Immunopathology of RSV infection: prospects for developing vaccines without this
      complication.
AB  - Respiratory syncytial virus is the most important cause of lower respiratory
      tract infection in infants and young children. RSV clinical disease varies from
      rhinitis and otitis media to bronchiolitis and pneumonia. An increased incidence
      of asthma later in life has been associated with the more severe lower
      respiratory tract infections. Despite its importance as a pathogen, there is no
      licensed vaccine against RSV. This is due to a number of factors complicating the
      development of an effective and safe vaccine. The immunity to natural RSV
      infection is incomplete as re-infections occur in all age groups, which makes it
      challenging to design a protective vaccine. Second, the primary target population
      is the newborn infant, which has a relatively immature immune system and maternal
      antibodies that can interfere with vaccination. Finally, some vaccines have
      resulted in a predisposition for exacerbated pulmonary disease in infants, which
      was attributed to an imbalanced Th2-biased immune response, although the exact
      cause has not been elucidated. This makes it difficult to proceed with vaccine
      testing in infants. It is likely that an effective and safe vaccine needs to
      elicit a balanced immune response, including RSV-specific neutralising
      antibodies, CD8 T-cells, Th1/Th2 CD4 T-cells and preferably secretory IgA.
      Subunit vaccines formulated with appropriate adjuvants may be adequate for
      previously exposed individuals. However, intranasally delivered genetically
      engineered attenuated or vectored vaccines are currently most promising for
      newborns, as they are expected to induce a balanced immune response similar to
      that elicited to natural infection and not be subject to interference from
      maternal antibodies. Maternal vaccination may be the optimal strategy to protect
      the very young infants.

PMID- 17004295
TI  - Stress and coping in hospice nursing staff. The impact of attachment styles.
AB  - Previous research suggests that the attachment style developed during childhood
      informs adult attachment styles, which in turn affects adult relationships and
      responses to stress. This study considers the sources of stress in hospice nurses
      and addresses the potential impact of their attachment styles on stress and
      coping experiences. Adult attachment style, stress and coping were measured in 84
      nurses recruited from five hospices. The results supported previous research
      regarding the most common sources of stress in this nursing group. The study
      found partial support for the hypothesis that nurses with insecure attachment
      styles experience more stress than securely attached nurses. Hospice nurses with
      a fearful or dismissing attachment style were found to be less likely to seek
      emotional social support as a means of coping with stress than hospice nurses
      with a secure or preoccupied attachment style. Supervision, support and career
      long training for nurses in hospices are recommended. Further research is needed
      to clarify the involvement of attachment style in hospice nurse stress and coping
      experiences.

PMID- 17004294
TI  - Diagnosis of congenital CMV infection via dried blood spots.
AB  - Cytomegalovirus (CMV) infection is the most frequent congenital infection in
      humans and can cause permanent damage--particularly neurological--in about 20% of
      those infected, with or without symptoms at birth. Laboratory diagnosis is
      essential on account of the relatively non-specific clinical manifestations in
      symptomatic newborns but also because of the high frequency of asymptomatic cases
      that are nevertheless at risk of lesions later in life. However, these tests need
      samples taken within 3 weeks of birth to distinguish congenital infection from
      the more common, but clinically benign, perinatal infection. Tests for viral DNA
      have proved a valid means of diagnosing congenital CMV infection in neonatal
      blood dried on paper (DBS) widely used in screening for metabolic and genetic
      diseases, as an alternative to the conventional urine culture method. The DBS
      test is simpler, faster and less costly than viral isolation; in addition the
      samples can be safely stored for long periods, so diagnosis can be made even
      after several years. The sensitivity and specificity of the DBS test, compared to
      the reference method, have been reported to range between 71 and 100% and 99 and
      100%, respectively, depending on the different studies and diagnostic criteria
      applied. The most interesting applications reported so far involve retrospective
      determination of the impact of congenital CMV in sensorineural deafness,
      abnormalities of cortical development, neonatal cholestasis and surveys of the
      prevalence of this infection in various populations. The test might be useful in
      the future for neonatal screening with a view to treating neonates and so
      avoiding the damage this disease can cause.

PMID- 17004296
TI  - A new approach for in vitro regeneration of tomato plants devoid of exogenous
      plant growth hormones.
AB  - Many available methodologies for in vitro regeneration of commercial tomato
      varieties promote not only the production of normal shoots but also individual
      leaves, shoots without apical meristems and vitrified structures. All these
      abnormal formations influence and diminish the regeneration efficiency. At the
      basis of this phenomenon lies callus development. We optimized an alternative
      procedure by which the regeneration occurs without abnormal shoot formation. The
      portion including the proximal part of hypocotyls and the radicle was cultured on
      medium consisting of Murashige and Skoog salts, 4 mg/L thiamine, 100 mg/L mio
      inositol and 3% sucrose. After two-three weeks, 60% explants showed adventitious
      shoot formation. No changes in the morphological characteristics of regenerated
      plants and fruits were observed as compared with parents. Karyotypic analysis of
      regenerated plants showed no variations in chromosome number. The optimized
      procedure offers the advantage of tomato plant regeneration avoiding callus
      formation, which enables normal plant recovery with an efficiency ranging from
      1.45 +/- 0.05 to 2.57 +/- 0.06 shoots per explant in Campbell-28, Amalia, Lignon,
      and Floradel cultivars.

PMID- 17004297
TI  - New insights into mechanisms of growth and beta-carotene production in Blakeslea
      trispora.
AB  - Blakeslea trispora (Mucorales) has economic importance because of its ability to
      produce large amounts of beta-carotene. To shed light on the actual point of
      induction and to shorten the following production process, germination and growth
      of its two mating types, (-) and (+), were observed separately, and the mating
      point was investigated in lab scale experiments. The (-) mating type showed much
      faster germination than the (+) type on solid medium and in Erlenmeyer flasks.
      However, after a first period, the (-) mating type grew clearly slower than the
      (+) type. In addition, the (-) type branched more vividly than the (+) type. A
      ratio of 30:1 of (-) and (+) type at an age of 20 h was found to achieve highest
      beta-carotene yields. Our results provide a comprehensive overview of Blakeslea
      trispora growth and its product synthesis.

PMID- 17004298
TI  - Expression of green fluorescent protein in pollen of oilseed rape (Brassica napus
      L.) and its utility for assessing pollen movement in the field.
AB  - Transgene movement via pollen is an important component of gene flow from
      transgenic plants. Here, we present proof-of-concept studies that demonstrate the
      monitoring of short distant movement of pollen expressing a genetically encoded
      fluorescent tag in oilseed rape (Brassica napus L. cv. Westar). Transgenic
      oilseed rape plants were produced using Agrobacterium-mediated transformation
      method with the pBINDC1 construct containing a green fluorescent protein (GFP)
      variant, mGFP5-ER, under the control of the pollen-specific LAT59 promoter from
      tomato. Transgenic pollen was differentiated from non-transgenic pollen in vivo
      by a unique spectral signature, and was shown to be an effective tool to monitor
      pollen movement in the greenhouse and field. GFP-tagged pollen also served as a
      practical marker to determine the zygosity of plants. In a greenhouse pollen flow
      study, more pollen was captured at closer distances from the source plant plot
      with consistent wind generated by a fan. Under field conditions, GFP transgenic
      pollen grains were detected up to a distance of 15 m, the farthest distance from
      source plants assayed. GFP-tagged pollen was easily distinguishable from non
      transgenic pollen using an epifluorescence microscope.

PMID- 17004299
TI  - Endoplasmic reticulum-retention C-terminal sequence enhances production of an 11S
      seed globulin from Amaranthus hypochondriacus in Pichia pastoris.
AB  - The methylotrophic yeast Pichia pastoris was used to express an 11S seed globulin
      from Amaranthus hypochondriacus. Three different plasmids were tested for
      expression of amarantin. One of them, which included the untranslated regions
      (UTR) of the full cDNA, failed to express the amarantin under tested conditions,
      whereas the other plasmids, one without UTR and the other similar but including
      the endoplasmic reticulum-retention signal KDEL, were able to express the
      proamarantin in P. pastoris. After 48 h of induction, KDEL-proamarantin had
      accumulated quite significantly compared to unmodified proamarantin. Different
      solubilization patterns were also obtained from both proamarantin versions; only
      soluble protein was obtained from the system that included the KDEL retrieval
      signal. Protein fractionation was carried out by differential precipitation with
      ammonium sulfate, and proamarantin purification was performed using an HPLC ion
      exchange column. The endoplasmic reticulum-retention C-terminal sequence (KDEL
      retrieval signal), not commonly employed in this heterologous expression system,
      can therefore be used to enhance accumulation of recalcitrant protein in P.
      pastoris. The results obtained here also suggest that this expression system is
      suitable for expression and evaluation of engineered seed globulin proteins.

PMID- 17004300
TI  - Evaluation of anti-methicillin-resistant Staphylococcus aureus (MRSA) activity
      and synergy of some bioactive plant extracts.
AB  - Anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of ethanolic
      extracts of four medicinal plants namely Acorus calamus (rhizome) Hemidesmus
      indicus (stem), Holarrhena antidysenterica (bark), and Plumbago zeylanica (root),
      were detected with inhibition zone size ranged from 11 to 44 mm and minimum
      inhibitory concentration (MIC) varied from 0.32 to 3.25 mg/mL. Further, ethyl
      acetate, acetone and methanol fractions of above plants demonstrated
      antibacterial activity. The potency of these fractions based on zone of
      inhibition and MIC value was relatively higher in P. zeylanica (ethylacetate
      fraction), followed by acetone fractions of H. indicus, A. calamus, and H.
      antidysenterica. Time kill assay with most promising fractions of these plant
      extracts, demonstrated concentration-dependent killing of MRSA within 9-12 h of
      incubation. Interestingly, synergistic interaction among alcoholic extracts and
      some fractions of above four plants was evident against MRSA. Further,
      synergistic interaction of these extracts was detected with one or more
      antibiotics tested (tetracycline, chloramphenicol, ciprofloxacin, cefuroxime and
      ceftidizime). The findings also validate the traditional uses of above plants
      against infectious diseases. Phytochemical studies demonstrated flavonoids and
      phenols as major active constituents. Further investigations are needed to
      characterize the active principle and its interaction mechanism with antibiotics.

PMID- 17004302
TI  - XVSAP1 from Xerophyta viscosa improves osmotic-, salinity- and high-temperature
      stress tolerance in Arabidopsis.
AB  - XVSAP1, a gene isolated from a dehydrated Xerophyta viscosa cDNA library, was
      transformed into Arabidopsis thaliana by Ti plasmid-mediated transformation under
      the control of a cauliflower mosaic virus 35S promoter, a nos terminator and bar
      gene selection. Expression of XVSAP1 in Arabidopsis led to constitutive
      accumulation of the corresponding protein in the leaves. Transgenic Arabidopsis
      grown in tissue culture maintained higher growth rates during osmotic, high
      salinity and high temperature stress, respectively. Non-transgenic plants had
      shorter roots, leaf expansion was inhibited and leaves were more chlorotic than
      those of the transgenic plants. This study demonstrates that XVSAP1 has a
      significant impact on dehydration, salinity and high-temperature stress tolerance
      in Arabidopsis.

PMID- 17004301
TI  - Plant growth promoting potential of free-living diazotrophs and other
      rhizobacteria isolated from Northern Indian soil.
AB  - The viable count of free-living diazotrophic bacteria in different crop
      rhizospheres varied from 1.11 x 10(4) to 8.5 x 10(5) CFU/g of soil. The majority
      of the diazotrophs phenotypically belong to either Azotobacter chroococcum, non
      A. chroococcum type and to a heterogenous group tentatively named putative
      nitrogen-fixing (PNF) bacteria. In this study, 25 isolates of the PNF group were
      screened for their multiple plant growth-promoting (PGP) traits and grouped into
      5 PGP types. An isolate, PNF(11) showed promising PGP potential in vitro and was
      characterized as a species of Achromobacter by 16S rRNA analysis. The isolate
      PNF(11) along with three other previously isolated PGP bacteria, Azotobacter sp.
      (AZS(3)), fluorescent pseudomonas (Ps(5)), Bacillus sp. (Bc(1)) were selected for
      crop inoculation response in green house experiment on Vigna radiata var.T44.
      Plants from inoculated and control pots were sampled and analyzed at 30, 45 and
      60 days after sowing for various vegetative, nodule-related data and yield
      parameters. The findings indicated that selected isolate of PNF bacteria, and
      other PGP isolates with multiple activities significantly improve the plant
      growth parameters, yield parameters of Vigna radiata T44 over control and also
      show good compatibility with Bradyrhizobium inoculation.

PMID- 17004303
TI  - Genetic analysis and epigenetic silencing of At4CL1 and At4CL2 expression in
      transgenic Arabidopsis.
AB  - 4-coumarate::CoA ligase (4CL) gene family members are involved in channeling
      carbon flow into branch pathways of phenylpropanoid metabolism. Transgenic
      Arabidopsis plants containing the At4CL1 or At4CL2 promoter fused to the beta
      glucuronidase (GUS) reporter gene show developmentally regulated GUS expression
      in the xylem tissues of the root and shoot. To identify regulatory genes involved
      in the developmental regulation of At4CL and other phenylpropanoid-specific
      genes, we generated ethyl methyl sulfate mutagenized populations of At4CL1::GUS
      and At4CL2::GUS transgenic lines and screened approximately 16,000 progeny for
      reduced or altered GUS expression. Several lines with reproducible patterns of
      reduced GUS expression were identified. However, the GUS-expression phenotype
      segregated in a non-Mendelian manner in all of the identified lines. Also, GUS
      expression was restored by 5-azacytidine (aza) treatment, suggesting inhibitory
      DNA methylation of the transgene. Southern analysis confirmed DNA methylation of
      the proximal promoter sequences of the transgene only in the mutant lines. In
      addition, retransformation of At4CL::GUS lines with further At4CL promoter
      constructs enhanced the GUS-silencing phenotype. Taken together, these results
      suggest that the isolated mutants are epimutants. Apparently, two different modes
      of silencing were engaged in the At4CL1::GUS and At4CL2::GUS silenced lines.
      While silencing in the seedlings of the At4CL1::GUS lines was root specific in
      seedlings, it affected all organs in the At4CL2::GUS lines. Also, At4CL1::GUS
      transgene silencing was confined to the transgene but At4CL2::GUS silencing
      extended to the endogenous At4CL2 gene. Organ-specific silencing of the
      At4CL1::GUS transgene cannot be explained by current models in the literature.

PMID- 17004304
TI  - Use of virus vectors for the expression in plants of active full-length and
      single chain anti-coronavirus antibodies.
AB  - To extend the potential of antibodies and their derivatives to provide passive
      protection against enteric infections when supplied orally in crude plant
      extracts, we have expressed both a small immune protein (SIP) and a full-length
      antibody in plants using two different plant virus vectors based on potato virus
      X (PVX) and cowpea mosaic virus (CPMV). The alphaSIP molecule consisted of a
      single chain antibody (scFv) specific for the porcine coronavirus, transmissible
      gastroenteritis virus (TGEV) linked to the alpha-CH3 domain from human IgA. To
      express the full-length IgA, the individual light and heavy chains from the TGEV
      specific mAb 6A.C3 were inserted into separate PVX constructs and plants were co
      infected with both constructs. Western blot analysis revealed the efficient
      expression of both the SIP and IgA molecules. Analysis of crude plant extracts
      revealed that both the plant-expressed alphaSIP and IgA molecules could bind to
      and neutralize TGEV in tissue culture, indicating that active molecules were
      produced. Oral administration of crude extracts from antibody-expressing plant
      tissue to 2-day-old piglets showed that both the alphaSIP and full-length IgA
      molecules can provide in vivo protection against TGEV.

PMID- 17004305
TI  - Production of biopharmaceuticals and vaccines in plants via the chloroplast
      genome.
AB  - Transgenic plants offer many advantages, including low cost of production (by
      elimination of fermenters), storage and transportation; heat stability; and
      absence of human pathogens. When therapeutic proteins are orally delivered, plant
      cells protect antigens in the stomach through bioencapsulation and eliminate the
      need for expensive purification and sterile injections, in addition to
      development of both systemic and mucosal immunity. Chloroplast genetic
      engineering offers several advantages, including high levels of transgene
      expression, transgene containment via maternal inheritance and multi-gene
      expression in a single transformation event. Hyper-expression of vaccine antigens
      against cholera, tetanus, anthrax, plague or canine parvovirus (4-31% of total
      soluble protein, tsp) in transgenic chloroplasts (leaves) or non-green plastids
      (carrots, tomato), as well as the availability of antibiotic-free selectable
      markers or the ability to excise selectable marker genes, facilitate oral
      delivery. Hyper-expression of several therapeutic proteins, including human serum
      albumin (11.1% tsp), somatotropin (7% tsp), interferon-gamma (6% tsp), anti
      microbial peptide (21.5% tsp), facilitates efficient and economic purification.
      Also, the presence of chaperones and enzymes in chloroplasts facilitate assembly
      of complex multi-subunit proteins and correct folding of human blood proteins
      with proper disulfide bonds. Functionality of chloroplast-derived vaccine
      antigens and therapeutic proteins has been demonstrated by several assays,
      including the macrophage lysis assay, GM1-ganglioside binding assay, protection
      of HeLa cells or human lung carcinoma cells against encephalomyocarditis virus,
      systemic immune response, protection against pathogen challenge, and growth or
      inhibition of cell cultures. Thus, transgenic chloroplasts are ideal bioreactors
      for production of functional human and animal therapeutic proteins in an
      environmentally friendly manner.

PMID- 17004306
TI  - Techniques of molecular oncology. Anatomy of the transcription apparatus.

PMID- 17004307
TI  - Essentials of modern immunology. HIV versus the immune system.

PMID- 17004308
TI  - Every cloud has a silver lining.

PMID- 17004310
TI  - Exclusion criteria important in use of clinical decision rules.

PMID- 17004311
TI  - Intramyocardial hydatic cyst in a young woman: Successful excision without
      cardiopulmonary by-pass.

PMID- 17004312
TI  - New acute coronary syndromes guidelines--addressing systems issues.

PMID- 17004313
TI  - ICM pilot project on training of midwives in HIV care.

PMID- 17004314
TI  - Resourcing global health: a conference of the Global Network of WHO Collaborating
      Centres for Nursing and Midwifery Development, Glasgow, Scotland, June 2006.

PMID- 17004315
TI  - Billing unveiled: calculating the value of emergency physician work.

PMID- 17004316
TI  - Only six percent of hospitals prepared for pediatric emergencies? The controversy
      and facts about the fearsome statistic.

PMID- 17004317
TI  - European Academy of Andrology membership list 2006.

PMID- 17004318
TI  - Abstracts of the 16th International Symposium on Regulatory Peptides, Hakone,
      Japan, August 30-September 2, 2006.

PMID- 17004320
TI  - Evidence for early endosome-like fusion of recently endocytosed synaptic
      vesicles.
AB  - Early endosomes are well-established acceptor compartments of endocytic vesicles
      in many cell types. Little evidence of their existence or function has been
      obtained in synapses, and it is generally believed that synaptic vesicles recycle
      without passing through an endosomal intermediate. We show here that the early
      endosomal SNARE proteins are enriched in synaptic vesicles. To investigate their
      function in the synapse, we isolated synaptic nerve terminals (synaptosomes),
      stimulated them in presence of different fluorescent markers to label the
      recycling vesicles and used these vesicles in in vitro fusion assays. The
      recently endocytosed vesicles underwent homotypic fusion. They also fused with
      endosomes from PC12 and BHK cells. The fusion process was dependent upon NSF
      activity. Moreover, fusion was dependent upon the early endosomal SNAREs but not
      upon the SNAREs involved in exocytosis. Our results thus show that at least a
      fraction of the vesicles endocytosed during synaptic activity are capable of
      fusing with early endosomes and lend support to an involvement of endosomal
      intermediates during recycling of synaptic vesicles.

PMID- 17004319
TI  - Ligand valency affects transcytosis, recycling and intracellular trafficking
      mediated by the neonatal Fc receptor.
AB  - The neonatal Fc receptor (FcRn) transports IgG across epithelial cell barriers to
      provide maternal antibodies to offspring and serves as a protection receptor by
      rescuing endocytosed IgG and albumin from lysosomal degradation. Here we describe
      the generation of polarized Madin-Darby canine kidney (MDCK) cells expressing rat
      FcRn (rFcRn) to investigate the potential requirement for ligand bivalency in
      FcRn-mediated transport. The rFcRn-MDCK cells bind, internalize and
      bidirectionally transcytose the bivalent ligands IgG and Fc across polarized cell
      monolayers. However, they cannot be used to study FcRn-mediated transport of the
      monovalent ligand albumin, as we observe no specific binding, internalization or
      transcytosis of rat albumin. To address whether ligand bivalency is required for
      transport, the ability of rFcRn to transcytose and recycle wild-type Fc
      homodimers (wtFc; two FcRn-binding sites) and a heterodimeric Fc (hdFc; one FcRn
      binding site) was compared. We show that ligand bivalency is not required for
      transcytosis or recycling, but that wtFc is transported more efficiently than
      hdFc, particularly at lower concentrations. We also demonstrate that hdFc and
      wtFc have different intracellular fates, with more hdFc than wtFc being
      trafficked to lysosomes and degraded, suggesting a role for avidity effects in
      FcRn-mediated IgG transport.

PMID- 17004321
TI  - Trafficking of HIV-1 RNA is mediated by heterogeneous nuclear ribonucleoprotein
      A2 expression and impacts on viral assembly.
AB  - Few details are known about how the human immunodeficiency virus type 1 (HIV-1)
      genomic RNA is trafficked in the cytoplasm. Part of this process is controlled by
      the activity of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2). The role
      of hnRNP A2 during the expression of a bona fide provirus in HeLa cells is
      investigated in this study. Using immunofluorescence and fluorescence in situ
      hybridization techniques, we show that knockdown of hnRNP A2 expression in HIV-1
      expressing cells results in the rapid accumulation of HIV-1 genomic RNA in a
      distinct, cytoplasmic space that corresponds to the microtubule-organizing center
      (MTOC). The RNA exits in the nucleus and accumulates at the MTOC region as a
      result of hnRNP A2 knockdown even during the expression of a provirus harboring
      mutations in the hnRNP A2-response element (A2RE), the expression of which
      results in nuclear retention of genomic RNA. We also demonstrate that hnRNP A2
      expression is required for downstream trafficking of genomic RNA from the MTOC in
      the cytoplasm. Genomic RNA localization at the MTOC that was both the result of
      hnRNP A2 knockdown and the overexpression of Rab7-interacting lysosomal protein
      had little effect on pr55Gag synthesis but negatively influenced virus production
      and infectivity. These data indicate that altered HIV-1 genomic RNA localization
      modulates viral assembly and that the MTOC serves as a central site to which HIV
      1 genomic RNA converges following its exit from the nucleus, with the host
      protein, hnRNP A2, playing a central role in taking it to and from this site in
      the cell.

PMID- 17004322
TI  - Dictyostelium RacH regulates endocytic vesicular trafficking and is required for
      localization of vacuolin.
AB  - Dictyostelium RacH localizes predominantly to membranes of the nuclear envelope,
      endoplasmic reticulum and Golgi apparatus. To investigate the role of this
      protein, we generated knockout and overexpressor strains. RacH-deficient cells
      displayed 50% reduced fluid-phase uptake and a moderate exocytosis defect, but
      phagocytosis was unaffected. Detailed examination of the endocytic pathway
      revealed defective acidification of early endosomes and reduced secretion of acid
      phosphatase in the presence of sucrose. The distribution of the post-lysosomal
      marker vacuolin was altered, with a high proportion of cells showing a diffuse
      vesicular pattern in contrast to the wild-type strain, where few intensely
      stained vacuoles predominate. Cytokinesis, cell motility, chemotaxis and
      development appeared largely unaffected. In a cell-free system, RacH stimulates
      actin polymerization, suggesting that this protein is involved in actin-based
      trafficking of vesicular compartments. We also investigated the determinants of
      subcellular localization of RacH by expression of green-fluorescent-protein
      tagged chimeras in which the C-terminus of RacH and the plasma-membrane-targeted
      RacG were exchanged, the insert region was deleted or the net positive charge of
      the hypervariable region was increased. We show that several regions of the
      molecule, not only the hypervariable region, determine targeting of RacH.
      Overexpression of mistargeted RacH mutants did not recapitulate the phenotypes of
      a strain overexpressing nonmutated RacH, indicating that the function of this
      protein is in great part related to its subcellular localization.

PMID- 17004323
TI  - Homologues of oxysterol-binding proteins affect Cdc42p- and Rho1p-mediated cell
      polarization in Saccharomyces cerevisiae.
AB  - Polarized cell growth requires the establishment of an axis of growth along which
      secretion can be targeted to a specific site on the cell cortex. How polarity
      establishment and secretion are choreographed is not fully understood, though Rho
      GTPase- and Rab GTPase-mediated signaling is required. Superimposed on this
      regulation are the functions of specific lipids and their cognate binding
      proteins. In a screen for Saccharomyces cerevisiae genes that interact with Rho
      family CDC42 to promote polarity establishment, we identified KES1/OSH4, which
      encodes a homologue of mammalian oxysterol-binding protein (OSBP). Other yeast
      OSH genes (OSBP homologues) had comparable genetic interactions with CDC42,
      implicating OSH genes in the regulation of CDC42-dependent polarity
      establishment. We found that the OSH gene family (OSH1-OSH7) promotes cell
      polarization by maintaining the proper localization of septins, the Rho GTPases
      Cdc42p and Rho1p, and the Rab GTPase Sec4p. Disruption of all OSH gene function
      caused specific defects in polarized exocytosis, indicating that the Osh proteins
      are collectively required for a secretory pathway implicated in the maintenance
      of polarized growth.

PMID- 17004324
TI  - Identification and characterization of associated with lipid droplet protein 1: A
      novel membrane-associated protein that resides on hepatic lipid droplets.
AB  - Alcoholic and nonalcoholic liver steatosis and steatohepatitis are characterized
      by the massive accumulation of lipid droplets (LDs) in the cytosol of
      hepatocytes. Although LDs are ubiquitous and dynamic organelles found in the
      cells of a wide range of organisms, little is known about the mechanisms and
      sites of LD biogenesis. To examine the participation of these organelles in the
      pathophysiological disorders of steatotic livers, we used a combination of mass
      spectrometry (matrix-assisted laser desorption ionization-time of flight and LC
      MS electrospray) and Western blot analysis to study the composition of LDs
      purified from rat liver after a partial hepatectomy. Fifty proteins were
      identified. Adipose differentiation-related protein was the most abundant, but
      other proteins such as calreticulin, TIP47, Sar1, Rab GTPases, Rho and actin were
      also found. In addition, we identified protein associated with lipid droplets I
      ALDI (tentatively named Associated with LD protein 1), a novel protein widely
      expressed in liver and kidney corresponding to the product of 0610006F02Rik
      (GI:27229118). Our results show that, upon lipid loading of the cells, ALDI
      translocates from the endoplasmic reticulum into nascent LDs and indicate that
      ALDI may be targeted to the initial lipid deposits that eventually form these
      droplets. Moreover, we used ALDI expression studies to view other processes
      related to these droplets, such as LD biogenesis, and to analyze LD dynamics. In
      conclusion, here we report the composition of hepatic LDs and describe a novel
      bona fide LD-associated protein that may provide new insights into the mechanisms
      and sites of LD biogenesis.

PMID- 17004325
TI  - Intrinsic tyrosine kinase activity is required for vascular endothelial growth
      factor receptor 2 ubiquitination, sorting and degradation in endothelial cells.
AB  - The human endothelial vascular endothelial growth factor receptor 2
      (VEGFR2/kinase domain region, KDR/fetal liver kinase-1, Flk-1) tyrosine kinase
      receptor is essential for VEGF-mediated physiological responses including
      endothelial cell proliferation, migration and survival. How VEGFR2 kinase
      activation and trafficking are co-coordinated in response to VEGF-A is not known.
      Here, we elucidate a mechanism for endothelial VEGFR2 response to VEGF-A
      dependent on constitutive endocytosis co-ordinated with ligand-activated
      ubiquitination and proteolysis. The selective VEGFR kinase inhibitor, SU5416,
      blocked the endosomal sorting required for VEGFR2 trafficking and degradation.
      Inhibition of VEGFR2 tyrosine kinase activity did not block plasma membrane
      internalization but led to endosomal accumulation. Lysosomal protease activity
      was required for ligand-stimulated VEGFR2 degradation. Activated VEGFR2
      codistributed with the endosomal hepatocyte growth factor-regulated tyrosine
      kinase substrate (Hrs)/signal-transducing adaptor molecule (STAM) complex in a
      ligand and time-dependent manner, implying a role for this factor in sorting of
      ubiquitinated VEGFR2. Increased tyrosine phosphorylation of the Hrs subunit in
      response to VEGF-A links VEGFR2 activation and Hrs/STAM function. In contrast,
      VEGFR2 in quiescent cells was present on both the endothelial plasma membrane and
      early endosomes, suggesting constitutive recycling between these two
      compartments. This pathway was clathrin-linked and dependent on the AP2 adaptor
      complex as the A23 tyrphostin inhibited VEGFR2 trafficking. We propose a
      mechanism whereby the transition of endothelial VEGFR2 from a constitutive
      recycling itinerary to a degradative pathway explains ligand-activated receptor
      degradation in endothelial cells. This study outlines a mechanism to control the
      VEGF-A-mediated response within the vascular system.

PMID- 17004326
TI  - Detection and quantification of protein-microtubules interactions using green
      fluorescent protein photoconversion.
AB  - We present an in vitro system to analyze quantitatively the interactions of green
      fluorescent protein (GFP)-tagged recombinant proteins with microtubules. This
      method relies on photoconversion of GFP and time-lapse microscopy. Specific
      interactions can be detected and binding kinetics can be determined rapidly and
      accurately. This method provides an alternative to classical in vitro microtubule
      binding assays to analyze microtubule-associated proteins binding to
      microtubules. It has the potential to be extended to study interactions of
      proteins or multi-protein complexes with different biopolymers like actin
      microfilaments or organelle membranes.

PMID- 17004327
TI  - Abstracts of the Joint Meeting of the European Society for Clinical Virology and
      the Clinical Virology Group of the Society for General Microbiology, Birmingham,
      United Kingdom, 3-6 September 2006.

PMID- 17004328
TI  - National Highway Traffic Safety Administration (NHTSA) notes. Analysis of
      speeding-related fatal motor vehicle crashes.

PMID- 17004329
TI  - SIOP 2006. Abstracts of the 38th Annual Conference on the International Society
      of Paediatric Oncology, Geneva, Switzerland, September 18-21, 2006.

PMID- 17004330
TI  - Muscle glutathione metabolism during ischemia and reperfusion in patients
      undergoing aorto-bifemoral bypass surgery.
AB  - BACKGROUND: After an ischemia time of 1 h during aortic aneurysm surgery, muscle
      glutathione redox-status is not altered, indicating that this ischemic insult is
      well within the scavenging capacity of muscle glutathione, the most important
      endogenous scavenger. In the present study, the impact of elective aorto
      bifemoral bypass surgery, involving a longer ischemia time, on muscle glutathione
      and its redox-status was investigated. METHODS: Leg muscle biopsies were obtained
      pre-operatively, at maximal ischemia, after 10 min and 24 h of reperfusion from
      12 patients undergoing aorto-bifemoral bypass surgery. Muscle glutathione, free
      amino acids and energy-rich compounds were determined. RESULTS: Clamping times
      were 113 (99-120 min); median (quartiles). At maximal ischemia, muscle lactate
      increased by 7.5 (4.0-10.7) mmol/kg dry weight (dw) (P < 0.001) and
      phosphocreatine (PCr) decreased by 14.6 (8.9-23.3) mmol/kg dw (P < 0.001). At
      maximal ischemia, reduced glutathione (GSH) was unaltered but muscle glutamate
      decreased by 0.51 (0.30-0.85) mmol/kg wet weight (ww) (P < 0.001). At 24 h post
      operatively, the reduced glutathione decreased by 0.47 (0.34-0.65) mmol/kg (ww)
      (P < 0.001) without changes in oxidized glutathione (GSSG) or in glutathione
      redox-status. Cysteine and glycine, the two other constituent amino acids to
      glutathione, did not change during the study period. CONCLUSION: Ischemia of 2 h
      during aorto-bifemoral bypass was associated with changes in muscle energy-rich
      compounds but without any changes in glutathione redox-status. A decreased
      antioxidative capacity, as reflected by a decrease in muscle glutathione
      concentrations, was seen 24 h post-operatively, still without changes in
      glutathione redox-status. This is not different from the changes seen after
      abdominal surgery not involving ischemia-reperfusion.

PMID- 17004331
TI  - Skin flowmetry: a new 'depth of anesthesia' monitor?

PMID- 17004332
TI  - Increased post-operative bleeding with non-steroidal anti-inflammatory drugs?

PMID- 17004333
TI  - An interchangeable Mapleson A-D breathing system.

PMID- 17004334
TI  - Outcome quality in the management of multiple casualty incidents.

PMID- 17004335
TI  - Abstracts of the 54th Annual Congress on Medicinal Plant Research, 29 August-2
      September 2006, Helsinki, Finland.

PMID- 17004336
TI  - Abstracts of the XXVI International Congress of the International Academy of
      Pathology, September 16-21, 2006, Montreal, Canada.

PMID- 17004337
TI  - Proceedings of the 19th European College of Neuropsychopharmacology (ECNP)
      Congress, Paris, France, 16-20 September 2006.

PMID- 17004338
TI  - Effect of deep breathing at six breaths per minute on the frequency of premature
      ventricular complexes.
AB  - Although the effect of reflex increase in vagal tone on the frequency of
      premature ventricular complexes (PVC) is known, the effect of timed deep
      breathing on the frequency of PVC has not been reported. We serendipitously
      discovered that deep breathing at six breaths per minute abolished PVC in an 18
      year-old female with frequent PVC, anxiety, and palpitations. In five of a series
      of 10 consecutive patients with frequent (> or = 10/min) unifocal PVC, deep
      breathing at 6 breaths/min reduced the frequency of PVC by at least 50%. This is
      possibly due to increased vagal modulation of sinoatrial and atrioventricular
      node. However, factors predicting the response to deep breathing, and the
      mechanisms involved need to be studied in a larger number of patients.

PMID- 17004339
TI  - [Proceedings and abstracts of the 7th National Infectious Disease Meeting,
      Bordeaux, France, 7-9 June 2006].

PMID- 17004340
TI  - Revision: implementation expectations for National Patient Safety Goal 3,
      requirement 3D.

PMID- 17004341
TI  - [Scientific and training conference: Contemporary threat by infectious diseases,
      Bydgoszcz 15-17 September 2005].

PMID- 17004342
TI  - Invited commentary.

PMID- 17004343
TI  - The influence of context on the success of adoptive breastfeeding: developing
      countries and the west.
AB  - It is commonly believed that adoptive mothers in developing countries are more
      successful breastmilk producers than women in the west. A review of published
      research supports this assertion. However, an examination of the practice of
      adoptive breastfeeding in developing countries and in the west via the literature
      reveals differences that may explain the variation in success. Adoptive mothers
      in developing countries may have greater milk production than mothers in the west
      because they are more knowledgeable about breastfeeding, practice frequent
      breastfeeding, remain in close physical contact with their children and live in
      cultures that are supportive of breastfeeding. They also have reproductive and
      breastfeeding histories that may make breastfeeding easier, though they are less
      likely to have pharmaceutical galactagogues available. Adoptive mothers in the
      west should be encouraged to maximise their milk supply by emulating the
      mothering styles of women in developing countries and developing a strong support
      network for breastfeeding. It may be that most adoptive mothers are physically
      capable of producing sufficient breastmilk for their child but that in the west,
      sociocultural factors act as preventatives.

PMID- 17004344
TI  - Factors influencing mothers' decision to breastfeed in public.
AB  - Breastfeeding in public was a major theme that emerged in a previous Western
      Australian study that explored the maternal process of managing breastfeeding and
      subsequent weaning. This paper highlights the factors that influenced mothers'
      decisions to breastfeed in public. Confidence with breastfeeding, the ability to
      be discreet, the mother's body image, previous experience, age of the
      breastfeeding child, the audience, feelings of the partner, breastfeeding
      location and perceptions of societal expectations all impacted upon the decision
      of how to manage breastfeeding in public. Initiatives to promote a breastfeeding
      friendly community are briefly discussed as well as strategies that participants
      employed to manage their breastfeeding in public. These findings add to our
      knowledge on breastfeeding and have implications for how we support breastfeeding
      women.

PMID- 17004345
TI  - Midwives' knowledge of newborn feeding ability and reported practice managing the
      first breastfeed.
AB  - Continuous uninterrupted skin-to-skin contact is known to facilitate newborn
      transition to extrauterine life, the ability to actively find the nipple and
      establishment of effective breastfeeding but is not promoted consistently in
      practice. The Newborn Feeding Ability Questionnaire (NFAQ) was developed to
      measure midwives' knowledge and practice in supporting the first breastfeed. The
      NFAQ was administered to 3 500 midwives in Australia through a mailed survey. A
      response rate of 31.6% (n=1 105) was achieved and the sample was representative
      of the national midwifery population for age sex, education and experience. Mean
      total score for knowledge was 85.94 (range 40-110 out of 110), SD=10.55) and mean
      practice score was 95.89 (range 57-117 out of 120), SD=9.19). Knowledge of
      newborn feeding ability was consistently associated with best practice in
      managing the first breastfeed. Almost all midwives reported that skin-to-skin
      contact for newborn infants immediately after birth was important, but few
      understood the significance of 'continuous uninterrupted' skin-to-skin contact to
      facilitate correct attachment and effective suckling. One-third reported
      separting mother and baby for routine interventions before allowing the
      opportunity to demonstrate pre-feeding behaviour or actually breastfeed. Although
      midwives attempt to ensure the first breastfeed is facilitated soon after birth,
      the practice of continuous uninterrupted skin-to-skin contact seems poorly
      understood and not uniformly practised. Further research is needed to investigate
      how midwives teach mothers' positioning and attachment for the first breastfeed.
      Education of midwives so they can optimally facilitate the first breastfeed is
      required to improve breastfeeding initiation rates.

PMID- 17004346
TI  - 'And not a drop to drink'--why water is harmful for newborns.
AB  - Breastmilk is a species-specific food, that is, milk made by human mothers for
      human infants, and thus is the only natural fluid appropriate for the newborn
      human. There is a plethora of information available discussing the dangers of
      water supplementation to babies. This article aims to collate the more recent
      research papers. Fully breastfed babies do not require water, even in the hottest
      weather. The dangers of newborn water intoxication, risk of reduction in
      breastmilk supply and early weaning as well as not following the Ten Steps to
      Successful Breastfeeding's step six, are discussed. The impact of the attitude of
      and information from influential persons in the mother's life is also noted.

PMID- 17004348
TI  - Doesn't the breast work anymore? A rant on the state of lactation advice today.
AB  - Grandmothers often find that their children parent differently, or get parenting
      advice different from what they themselves learned as young mothers. When that
      happens, it can give the grandmother a feeling that what she did as a mother was
      invalid. When I became a grandmother, I considered myself lucky. I was a
      practicing paediatric nurse-practitioner and teaching in a university; as new
      studies came along that suggested making changes in the way people parented, I
      could understand and accept them from a medical point of view without feeling
      invalidated as a mother.

PMID- 17004347
TI  - Snoring and sleep apnoea: how it can be prevented in childhood.
AB  - Obstructive sleep apnoea (OSA) is a very serious health problem in our society
      today. Medical consequences are significant, health-care costs high and good
      treatment options limited. The best treatment is prevention. This article
      addresses the issue.

PMID- 17004349
TI  - HIV prophylaxis following sexual exposure.

PMID- 17004350
TI  - Use of steroids for wasting and lipodystrophy syndromes in HIV/AIDS.

PMID- 17004351
TI  - Wasting and lipodystrophy in patients infected with HIV: a practical approach in
      clinical practice.
AB  - The care of patients who have HIV infection must address multiple medical,
      psychological, and socioeconomic factors. Because of the time constraints of a
      typical 15-minute office visit, important issues may be overlooked unless the
      physician has a clear concept of priorities and a clear method of tracking
      information. Although the medical aspects--viral control--must take priority, the
      psychological and social consequences of the illness must not be ignored.
      Nutritional evaluation and counseling must be addressed because nutritional
      disturbances often adversely affect the general health of patients who are
      infected with HIV. Important nutritional complications of HIV infection are the
      syndromes of wasting and lipodystrophy. However, the onset of wasting may not be
      heralded by a change in the patient's weight. In patients who have AIDS, the
      mechanism leading to a loss of skeletal muscle mass has not been identified. HIV
      related lipodystrophy consists of accumulation of fat in the subcutaneous tissues
      of the lower trunk, abdominal viscera, and dorsocervical region with loss of fat
      from the upper and lower extremities, buttocks, and face. Lipodystrophy in
      association with HIV infection is not the same as the wasting syndrome of protein
      energy malnutrition. An early sign of lipodystrophy is facial wasting. The
      treatment of the nutritional complications of HIV infection includes exercise;
      nutritional counseling; and in selected patients, androgenic hormones, anabolic
      steroid hormones, and human growth hormone.

PMID- 17004352
TI  - Use of androgens in patients who have HIV/AIDS: what we know about the effect of
      androgens on wasting and lipodystrophy.
AB  - Decreases in energy, sense of well-being, libido, muscle strength, and muscle
      mass occur often in patients who have chronic diseases, such as HIV infection.
      When these symptoms were first recognized in HIV-positive patients, they were
      thought to be manifestations of HIV infection but may possibly be associated with
      hypogonadism. Most HIV-infected patients who have hypogonadism have secondary or
      central hypogonadism, not primary testicular failure. In HIV-infected hypogonadal
      men, administration of testosterone appears to increase fat-free mass, muscle
      mass, and quality of life (increased libido, erectile function, and sense of well
      being). Similarly, anabolic steroid hormones appear to increase lean body weight
      and decrease fat content. Although androgens have been used for the treatment of
      HIV-related wasting and for hypogonadism, many questions remain unanswered,
      including those regarding the long-term effects, if any, of suppression of
      luteinizing hormone and follicle-stimulating hormone, as well as the long-term
      possibilities of malignancy of the prostate and of hepatocellular cancer.
      Appropriate doses of the various preparations of testosterone and anabolic
      steroids have not been determined.

PMID- 17004353
TI  - Use of steroids for self-enhancement: an epidemiologic/societal perspective.
AB  - Humans are basically competitive. For centuries, athletes have used various
      substances to enhance performance, increase strength, and prolong endurance. In
      the early 1940s, research indicating that testosterone improved a sense of well
      being, appearance, and sexual performance led to the use of anabolic steroid
      hormones by a select few athletes. Today, even among high school students, the
      use of androgenic steroid hormones is prevalent, with 1% to 2% of adolescent
      girls and 4% to 6% of adolescent boys having used an anabolic steroid at least
      once. An estimated 1 million people in the United States are current of former
      users of anabolic-androgenic steroid hormones, with men having a higher
      prevalence of use than women. Androgenic steroid use has been associated with the
      use of other illicit drugs, cigarette smoking, and alcohol use. Nevertheless,
      anabolic-androgenic steroid hormones appear to have legitimate uses in certain
      patients. In HIV-infected, hypogonadal men, anabolic steroid hormones optimize
      muscle strength and muscle mass when combined with resistance exercise. Although
      a large number of people have used these drugs for many years, no studies of the
      long-term health effects have been done. However, when taken in supraphysiologic
      doses, these drugs are known to cause a wide range of acute adverse effects. When
      used in less then supraphysiologic doses in eugonadal or hypogonadal HIV-infected
      patients, these drugs reverse HIV-related hypogonadism, muscle wasting, and
      perhaps lipodystrophy. Provided that the oral preparations are not used and
      patients are closely monitored, anabolic-androgenic steroid hormones offer HIV
      infected patients a better quality of life and an improved sense of well-being.

PMID- 17004354
TI  - Misinterpretation of drinking water quality monitoring data with implications for
      risk management.
AB  - A survey of two groups of environmental professionals was conducted to explore
      the degree of understanding in the interpretation of monitoring results for
      informing decision-making and responding to data appropriately to manage
      environmental health risks. Specifically, the understanding of the predictive
      value of a monitoring result and the appreciation that false positive results
      will inevitably predominate when monitoring for rare or infrequent hazards was
      explored. Results indicate evidence of misinterpretation and overconfidence in
      the meaning of monitoring results, and the ability of laboratory methods to
      detect reliably an infrequent hazard in environmental samples. A hypothetical
      monitoring scenario was presented with characteristics sufficient to estimate
      what level of confidence was warranted in a positive result. The majority of
      respondents in both groups (most of whom had more than 10 years experience in
      their field) reported between very likely to almost certain confidence (80-100%
      likelihood) in a hypothetical monitoring result which was, in fact, less than 5%
      likely to be correct. Additionally, there was little influence of the beliefs
      expressed about the validity of the monitoring result on the actions proposed to
      be taken in response to finding that monitoring result. The independence of
      respondents' follow-up action to what they believe of a monitoring result implies
      a level of detachment between the understanding of the monitoring data and the
      resulting risk management response.

PMID- 17004355
TI  - Helmet use saves lives.

PMID- 17004356
TI  - Thoughts on specialists leaving academia for practice.

PMID- 17004357
TI  - Comments on the AVMA'S role in food animal medicine.

PMID- 17004358
TI  - [Image of the week. Norwegian scabies].

PMID- 17004359
TI  - Clinical challenges and images in GI: Image 1: Petit's (inferior lumbar) hernia.

PMID- 17004360
TI  - Clinical challenges and images in GI: Image 2: Deep venous thrombosis due to
      idiopathic megarectum and giant fecaloma.

PMID- 17004361
TI  - Progress in the history of Alzheimer's disease: the importance of context.
AB  - The history of Alzheimer's disease (AD) is typically formulated as the history of
      great doctors and scientists in the past making great discoveries that are in
      turn taken up by great doctors and scientists in the present--all sharing the aim
      of unraveling the mysteries of disease and discovering how it can be prevented or
      cured. While it can certainly be edifying to study the "great men" and how their
      contributions laid the foundation for current work, there are problems with this
      approach to history. First, it oversimplifies the actual historical development
      of science. Second, using history to legitimate the present can keep us from
      asking critical questions about the aims and limits of contemporary research.
      This chapter urges a broader view of the history of AD, one that recognizes that
      context is as important as the great doctors to the historical development of the
      concept of AD. Thought of this way, I argue that it is useful to divide of the
      history of AD into three periods. First there was the period in which Alzheimer
      and Kraepelin laid the clinical and pathological foundations of the disease
      concept. Then there is our own period, which began in the late 1970s and has
      emphasized the biological mechanisms of dementia. In between, there is the period
      - almost completely ignored in most histories of AD--that conceptualized dementia
      in psychodynamic terms. It is true that the psychodynamic model of dementia did
      not directly contribute to the concepts and theories that dominate AD research
      today. But it did change the context of aging and dementia in important ways,
      without which AD could not have emerged as a major disease worthy of a massive,
      publicly supported research initiative.

PMID- 17004362
TI  - 100 Years of Alzheimer's disease (1906-2006).
AB  - As we commemorate the first centennial since Alzheimer's disease (AD) was first
      diagnosed, this article casts back into the past while also looking to the
      future. It reflects on the life of Alois Alzheimer (1864-1915) and the scientific
      work he undertook in describing the disorder suffered by Auguste D. from age 51
      to 56 and the neuropathological findings revealed by her brain, reminding us of
      the origin of the eponym. It highlights how, throughout the 1960's, the true
      importance of AD as the major cause of late life dementia ultimately came to
      light and narrates the evolution of the concepts related to AD throughout the
      years and its recognition as a major public health problem. Finally, the article
      pays homage to the work done by the Alzheimer's Association and the research
      undertaken at the Alzheimer's Disease Centres within the framework of the
      National Institute on Aging (NIA) Program, briefly discussing the long road
      travelled in the fight against AD in the past 25 years and the scientific odyssey
      that we trust will result in finding a cure.

PMID- 17004364
TI  - My own experience in early research on Alzheimer disease.
AB  - This brief paper reviews the work on dementia by the Neuropathology group at the
      Einstein College of Medicine and later at the University of California, San
      Diego, from the time of our first approaches to Alzheimer Disease in 1959. The
      electron microscope studies concerned the tangle (got it wrong) and then the
      plaque (got it right). Lysosomes and active mitochondria were noted in the
      plaques. Axoplasmic transport was suggested to be abnormal. We studied the
      plaques in old dogs and old monkeys, and then went on to use image analysis to
      count neurons in the neocortex of Alzheimer cases and in examples of normal
      aging. Later in San Diego we quantified presynaptic boutons and recognized their
      loss as the major direct cause of dementia. Many collaborators including Henry
      Wisniewski participated in these early attempts to understand the disease.

PMID- 17004363
TI  - Neurodegeneration and hereditary dementias: 40 years of learning.
AB  - The invitation to participate in the commemorative issue celebrating the 100 th
      anniversary of Dr. Alois Alzheimer's report on the disease that would later bear
      his name has evoked memories of my early experiences in the study of dementia, my
      teachers, my role-models, my aspirations and my accomplishments. Early in my
      career, I was fascinated with the study of hereditary neurological disorders. The
      observation of families in which dementia was inherited in an autosomal dominant
      pattern excited my scientific curiosity. Three very different phenotypes in
      patients from three separate families have been the basis for novel scientific
      discovery, which has taken place over the past 30 years. This could not have
      taken place without the help of many generous patients and their families as well
      as wonderful colleagues for whom I am deeply grateful. Some of the original
      observations in these families have led to the discovery of genetic mutations in
      three genes that are among the most commonly affected in hereditary dementia. The
      work on these families has enriched the scientific community and our knowledge of
      dementing illnesses.

PMID- 17004365
TI  - Aluminum and Alzheimer's disease, a personal perspective after 25 years.
AB  - It is now 25 years since the publication of our original paper investigating the
      association aluminum with Alzheimer's disease. This publication reported on the
      results of scanning electron microscopy coupled x-ray spectrometry microprobe
      elemental studies of both neurofibrillary tangle-bearing and tangle-free neurons
      in the hippocampus of cases of Alzheimer's disease and controls. Peaks related to
      the presence of aluminum were consistently detected within the tangle-bearing
      neurons. This paper supported the association of aluminum and Alzheimer's disease
      on the cellular level of resolution and caused considerable interest and
      discussion. Subsequent work demonstrated prominent evidence of aluminum
      accumulation in the tangle-bearing neurons of cases of amyotrophic lateral
      sclerosis/parkinsonism-dementia complex of Guam. This latter observation has now
      been replicated using five different forms of microanalysis. Finally, using laser
      microprobe mass analysis, we demonstrated that the abnormally high aluminum
      related signal which we originally detected was actually located within the
      neurofibrillary tangle, itself, and was accompanied by excess concentrations of
      iron. Although it is unlikely that aluminum represents an etiologic cause of
      Alzheimer's disease, we believe that this highly reactive element, known to cross
      link hyperphosphorylated proteins, may play an active role in the pathogenesis of
      critical neuropathologic lesion in Alzheimer's disease and other related
      disorders.

PMID- 17004366
TI  - Solving the insoluble.
AB  - Dissection of neurofibrillary tangles has been confounded by the insolubility of
      their fibers. While the majority of biochemical studies have considered tau
      filaments equivalent to neurofibrillary tangles, they forget that the former are
      soluble and the latter completely resistant to solvents. What, then, accounts for
      the insolubility of neurofibrillary tangles while tau filaments are soluble?
      Investigation of these distinctions played a critical role in our findings on
      proteolytic abnormalities and oxidative stress.

PMID- 17004367
TI  - Sibling bereavement and continuing bonds.
AB  - Historically, from a Freudian and medical model perspective, emotional
      disengagement from the deceased was seen as essential to the successful
      adaptation of bereavement. A major shift in the bereavement literature has
      occurred and it is now generally accepted that despite the permanence of physical
      separation, the bereaved remains involved and connected to the deceased and can
      be emotionally sustained through continuing bonds. The majority of literature has
      focused on adults and on the nature of continuing bonds following the death of a
      spouse. In this article, the authors demonstrate how the continuing bonds concept
      applies to the sibling relationship. We describe the unique continued
      relationship formed by bereaved children and adolescents following a sibling
      loss, highlight the factors that influence the siblings continuing bonds
      expressions, and offer clinical interventions. In our view, mental health
      professionals can play an important role in helping parents encourage activities
      that may facilitate the creation and maintenance of continuing bonds in their
      children.

PMID- 17004368
TI  - Continuing conversation about continuing bonds.
AB  - The article is a response to the contributions the special issue of Death Studies
      on continuing bonds. The contributions indicate that the conversation among
      scholars has clarified our thinking on how bonds function in individual grief.
      The author discussed two issues to help keep the conversation moving: (a) the
      relationship of continuing bonds to the complex we call adjustment to or
      resolution of grief, and (b) the social and communal nature of continuing bonds.
      In the first, the author concluded that the hypothesis that continuing bonds
      either help or hinder grief adjustment too simple to account for the evidence. In
      the second, he argued that cultural/political narratives are woven into
      individual grief narratives and if we do not include community, cultural, and
      political narratives in our understanding of continuing bonds we are in danger
      building bereavement theory that applies to only a small portion of one
      population in one historical time.

PMID- 17004369
TI  - Characteristics of suicide from 1998-2001 in metropolitan area.
AB  - In order to establish effective suicide preventive programs, it is important to
      know the etiologic factors and causal relationships between suicide and behavior.
      Coroner data was analyzed for the 468 suicides that occurred in Indianapolis,
      Indiana during 1998-2001. The age-adjusted suicide rate was 14.08 per 100,000.
      Almost one-half of the victims had a mental illness and 26% had a history of
      alcohol/substance abuse. The leading risk factors for suicide were age, impaired
      health, psychosocial stressors, and access to firearms. This information can be
      used by health departments and mental health professionals to help reduce
      suicide.

PMID- 17004370
TI  - Fourth Annual Asklepion Award goes to Dr. Lowell Ozment.

PMID- 17004371
TI  - A unilateral tubal twin pregnancy.

PMID- 17004372
TI  - [What is your diagnosis? Answer: Epidermoid inclusion cyst in a lymph node].

PMID- 17004373
TI  - [Dynamics of mortality of able-bodied population in CIS countries].
AB  - Comparative analysis founded on WHO European database was carried out concerning
      mortality in progress as compared between Russia and CIS countries. It is
      testified that the Russian Federation is distinguished by excelling rate of
      reduction of able-bodied population of middle age group. It is suggested that in
      this process significant role is played by health care system defects along with
      life-style factors. Motivation for enhancing activity and attention of medical
      workers as related to this age group, especially males is needed.

PMID- 17004375
TI  - [On prevention of oncological involutory complications].
AB  - Actual issues of modem medicine meeting basic directions of reformation of
      national public health system and enhancement of preventive services to female
      patients of various age groups are considered. Actual information on development
      of oncological gynecological diseases in women with complicated involutional
      period is included. Possibility in getting new data on risk factors in women with
      involutional period for the purpose of health promotion in women of reproductive
      age and of enhancement of life quality during involutional period is surmised.
      Prospective and effective pattern of primary prevention of oncological
      gynecological involutional pathology is proposed to be implemented in practice of
      public health cervices as standardized normative document.

PMID- 17004376
TI  - [Actual state and perspectives of development of regional health care exemplified
      by Republic of Tatarstan].

PMID- 17004374
TI  - [Aging of population in Russia as cause of increase in mortality from diseases of
      blood circulation system].

PMID- 17004377
TI  - [On reforming of pediatric service].
AB  - Results of processing, summarizing and analysis of data of special sociological
      survey are represented. Questionnaire in combination with sampling interview of
      workers of management units of okrug medical institutions, chief medical officers
      and heads of departments in pediatric clinics of City of Moscow was applied.
      Using megapolis pattern, the need in transformation of functioning of primary
      pediatric care institutions is validated. Issues of training of district
      paediatrician on pre-graduate and postgraduate stages are discussed. Specific
      suggestions related to problems of organization and management of medical and
      medical social care of children and adolescents are grounded.

PMID- 17004378
TI  - [Quality of life in children].

PMID- 17004379
TI  - [Problems of registration of morbidity and ways of its improvement].
AB  - New system of registration of primary morbidity was developed for the purpose of
      elimination of systemic error factors and decrease of human element input. The
      following principles are included: simplification of registration rules; more
      exact registration of acute conditions; unified rules of registration for out
      patient and in-patient medical institutions; unified form of information fields
      in medical documentation for morbidity registration in out-patient and in-patient
      medical institutions; succession in basic parameters, indicators and terms of
      medical statistics in currently in force and modernized systems. New system
      includes following information fields: "stage of diagnostics", "urgency of
      condition"; "ICD-10 code", "diagnosis", "life identification", "calendar year
      identification". All fields, except field "diagnosis", are formalized and for
      them (except field "ICD-10 code") corresponding codings are developed. Rules for
      filling information fields, algorithms of validity control of primary information
      and receiving such indicators as first time identified morbidity", "chronic
      morbidity", "emergency (acute) morbidity", "chronic sickliness/morbidity
      identified for the first time in previous years", "chronic sickliness" are
      developed. This system is implemented experimentally in medical institutions of
      primary and secondary levels of health care system in Yakka-Saraysk district of
      City of Tashkent.

PMID- 17004380
TI  - [Problems of evaluation of medical care effectiveness].

PMID- 17004381
TI  - [Characteristics of marketing complex formation in rendering of sanatorium resort
      services].
AB  - Basic positions in sanatorium resort marketing and its evolution with description
      of its main components are considered. Marketing research management in
      sanatorium resort institutions, marketing theory, analysis of services market,
      characteristics of marketing complex formation are presented.

PMID- 17004382
TI  - [Criteria of effectiveness and ways of enhancement of emergency medical care to
      newborns in Saratov oblast].
AB  - Basic parameters and problems of development of neonatal care in Saratov oblast
      are presented. Important part of neonatal care system is pediatric reanimation
      consulting center which functionally combine neonatal service and pediatric
      sanitary aviation service. Functionality of center includes rendering of
      consulting care by "Dynar"--system of remote monitoring by anaesthesiologist
      reanimatologist, visits to districts of oblast and patient transportation. Center
      activities and the training of medical workers of maternity departments, situated
      on all territory of region contributed to decreasing of infant mortality.

PMID- 17004384
TI  - [Nursing staff education in Brunei].
AB  - The only form of medical education in Brunei was nurse staff training until
      Institute of Medicine of University Brunei Darussalam was established in
      September 2000. In Brunei, nurse education was organized in 1951 when first group
      of students in School of Nursing was formed. In 1953 they received certificate of
      Trained Assistant Nurse. In 1954 more elaborated program of nurse training was
      introduced. Until 1986, in School of Nursing two levels of educational programs
      were used--General Nurse Training and Assistant Nurse Training. In 1986, College
      of Nursing was set up for training higher education nurses. In 1991 first
      graduates of college of nursing received diplomas of nursing. In 1999 School of
      Nursing was unified with College of Nursing which became the only educational
      institution for nurse training. Organizational structure and educational staff of
      College of Nursing, conditions of entering and diploma issues, curriculum and
      education courses, post-graduate training and international cooperation are
      discussed.

PMID- 17004383
TI  - [Medical social care in family planning].
AB  - Basic pattern of medical social work, including its main directions and objects,
      methods and forms are considered. Necessity of adoption of medical social work in
      functioning of institutions of family planning is validated. Groups of clients as
      objects of medical social work are considered. Content, forms and methods of
      medical social work in family planning institutions differentiated depending on
      particular client group is analyzed.

PMID- 17004385
TI  - [Teaching of pathology on medical faculty of Moscow University in XVIII century:
      report I. Purposes and objectives of course of pathology in XVIII century].

PMID- 17004386
TI  - [Concept of fighting alcoholism developed by V. M. Bekhterev in the beginning of
      XX century].

PMID- 17004387
TI  - [Beginnings of municipal self-governments' medicine in Russia (XVIII-first half
      of XIX century)].

PMID- 17004388
TI  - [Russian physicians of XVIII-XIX centuries on venereal diseases].

PMID- 17004389
TI  - What are good business practices, anyway?

PMID- 17004390
TI  - What every nurse needs to know about body piercing.

PMID- 17004391
TI  - STUDY TOURS: getting the most out of study tours.

PMID- 17004392
TI  - Hardiness training among nurse managers: building a healthy workplace.
AB  - BACKGROUND: This exploratory study investigated development of a model hardiness
      training program to determine whether stress could be reduced and hardiness could
      be increased and sustained among nurse managers. METHOD: Thirteen nurse managers
      at an urban hospital completed pretests for hardiness levels and underwent
      initial hardiness training for 2.5 days. Posttests were completed after initial
      training, after the 6 weekly sessions, and after 6 and 12 months. RESULTS:
      Changes in hardiness scores between pretest and the first posttest were
      significant (p < .05). Scores after the third posttest were decreased for the
      subscale control but were unchanged for subscales commitment and challenge.
      CONCLUSION: Findings suggest that the use of a hardiness training program and
      intermittent follow-up can be effective in increasing and sustaining hardiness
      levels in nurse managers and may have a positive impact on staff turnover rates.

PMID- 17004393
TI  - Tool kit for the staff mentor: strategies for improving retention.
AB  - Retention of new graduates in nursing continues to be a significant workplace
      issue, particularly in light of the heightening nursing shortage. Experienced
      nurses are in a pivotal position to positively impact retention, and, because of
      this, they can be called "keystoners". Mentoring, an important role of the
      keystoner, requires specific skills and knowledge and can be learned. A tool kit
      designed to develop the mentoring skills of keystoners is described. The result
      of successful mentoring among keystoners can be multifaceted; workplace
      satisfaction and higher retention of new graduates are targeted outcomes.

PMID- 17004395
TI  - Relationship of frequent mantram repetition to emotional and spiritual well-being
      in healthcare workers.
AB  - BACKGROUND: Healthcare workers report high levels of stress in the workplace. To
      determine how to reduce stress, the authors examined the effectiveness of
      frequently repeating a mantram (a word with spiritual meaning) on emotional and
      spiritual well-being. METHODS: A pretest-posttest design was used to measure
      stress, state/trait anxiety and anger, quality of life, and spiritual well-being
      in a convenience sample (N=42) of hospital workers completing a mantram
      intervention program. RESULTS: Significant improvements were found in stress (p <
      .001), trait-anxiety (p = .002), trait-anger (p = .02), quality of life (p =
      .001), and spiritual well-being (p = .003). When examining the effects of mantram
      practice, trait-anxiety and religious and spiritual well-being were significant
      (p < .05). CONCLUSION: Improvements in emotional and spiritual well-being may be
      mediated by frequent mantram repetition.

PMID- 17004394
TI  - Development, implementation, and evaluation of a geriatric nurse education
      program.
AB  - Substantial gaps exist between the number of older adults requiring competent
      geriatric care and the number of nurses able to provide it. The purpose of this
      study was to develop, implement, and evaluate a geriatric nurse education program
      to ensure nurses meet the needs of the increasing elderly population.
      Establishing partnerships between individuals in academia and those in a clinical
      practice was imperative in the development of the program. Content for the
      program was created with the assistance of a geriatric nursing consultant and
      approved by the State Nurses Association. The program was piloted with 18
      participating nurses. Using paired ttests, pretests and posttests revealed
      significant improvements in the level of knowledge and attitudes toward older
      adults. As a result of the program, participants showed improved attitudes toward
      and increased knowledge of older adults' needs, and further program development
      and dissemination are planned nationally and abroad.

PMID- 17004396
TI  - An evaluative case study of online learning for healthcare professionals.
AB  - BACKGROUND: This evaluation study assessed the pedagogical and instructional
      design (e-pedagogy) effectiveness of online continuing professional education
      (CPE) courses offered by a large Australian CPE provider. METHODS: A naturalistic
      theory approach and a multilevel evaluation were used to examine the impact of
      web-based learning on more than 300 healthcare professionals. Participant
      satisfaction, learning achievement, self-reported practice performance change,
      and e-pedagogical courseware characteristics were assessed by various qualitative
      and quantitative data collection methods. RESULTS: Findings revealed that
      learning online was an effective means for increasing CPE knowledge (p < .05) and
      improving self-reported practice performance change (p < .05). Courses containing
      a clinical tool resulted in an increased self-reported practice performance
      change over courses that did not (Zobs = 3.757). CONCLUSION: Online CPE offers a
      convenient format for healthcare professionals from educationally and
      geographically diverse populations to update their knowledge and view best
      practice.

PMID- 17004397
TI  - Enhancing cardiac rehabilitation nursing through aligning practice to theory:
      implications for nursing education.
AB  - This article presents a case study that examined the work practice of nurses in a
      cardiac step-down unit (CSDU). The action research included interviews,
      participant observation, and a self-reporting questionnaire. Nurses in the unit
      used a conceptual framework that was inconsistent with the rehabilitation
      oriented nursing necessary to enhance patient outcomes in a CSDU. The results of
      this study show that a need exists for greater alignment between the practice and
      the educational preparation of nurses who work in a CSDU. A framework such as
      Dorothea Orem's Self-Care Theory of Nursing (1995) offers a conduit for nurses to
      deliver care appropriate to CSDU patient needs. However, there is a need for
      continuing education for nursing staff to align the cardiac rehabilitation
      nursing philosophy and the theories that underpin it (such as the Self-Care
      Theory) with nursing practice. Practice development provides a mechanism through
      which to examine the congruence between patient needs and nurse perception of
      those needs.

PMID- 17004398
TI  - Mr Stuthridge's forthright letter regarding my recent article.

PMID- 17004400
TI  - Integrated medicine: good intentions, poor logic?

PMID- 17004399
TI  - Beyond belief?

PMID- 17004401
TI  - Complementary and alternative medicine: why I'm opposed to integration.

PMID- 17004402
TI  - Promoting health and well-being: the role of spirituality.

PMID- 17004403
TI  - Hypnotherapy! Just what the doctor ordered!

PMID- 17004404
TI  - Is homeopathy possible?
AB  - As a therapeutic intervention, homeopathy is the target of increased scepticism
      because in the main, its remedies are diluted and succussed (potentized) out of
      material existence. This puts homeopathy seemingly at odds with the paradigm of
      conventional science, in particular, that atoms and molecules are the fundamental
      building blocks of all matter. Accordingly, homeopathy cannot work, so that any
      reported beneficial effects must, at best, be due to the placebo effect. The
      purpose of this article is to challenge that conclusion and to suggest that there
      may well be conventional science-based explanations of how homeopathy could be
      possible. Homeopathy's key principles are first described. Then the double-blind
      randomized controlled trial (RCT), the chief means by which homeopathic remedies
      and prescribing are tested, is shown to be based on a linear reductionism that is
      too blunt an instrument with which to test the efficacy of complex interventions
      such as homeopathy The memory of water hypothesis, as a mechanism for how
      potentized remedies might work, is reviewed, along with some evidence for its
      existence. A possible rationale for the water memory effect is proposed in terms
      of a dynamic 'ordering' of water's constantly switching network of intermolecular
      hydrogen bonds, induced by the manufacturing process of homeopathic remedies.
      This could lead to a long-range molecular 'coherence' between trillions of mobile
      water molecules. However, the water memory effect is an essentially
      pharmacological explanation of homeopathy's putative efficacy. It is pointed out
      that healing also entails an interaction between consenting beings. From this
      point of view, an explanation of any therapeutic procedure should include an
      attempt to describe the nature of the patient-practitioner interaction. From this
      perspective, a quantum theoretical treatment of the therapeutic process,
      involving a form of macro-entanglement between patient, practitioner and remedy
      (PPR), is advanced as another possible explanation of the homeopathy's efficacy.
      This shows that the reason double-blind RCTs deliver at best only equivocal
      results on homeopathy's efficacy is because it effectively breaks the PPR
      entangled state. A comparison is made between the entanglement-breaking effect of
      double-blind RCTs and the wave-function 'collapsing' effect of observation in
      orthodox quantum theory. The article concludes by suggesting that the memory of
      water and PPR entanglement are not competing but most likely complementary
      hypotheses, and that both are probably required in order to provide a complete
      description of the homeopathic process. While awaiting experimental evidence of
      these hypotheses, it is suggested that observations of clinical outcomes would be
      superior to RCTs for further testing homeopathy's efficacy.

PMID- 17004405
TI  - A background to acupuncture and its use in chronic painful musculoskeletal
      conditions.
AB  - This article gives a brief description of the origins of acupuncture and
      describes some of the underlying philosophy behind this treatment and attempts to
      place it in context of the traditional Chinese medicine genre within which
      acupuncture is set. The article then explains the difference between traditional
      and Western style acupuncture and explains how point selection is made. The use
      of acupuncture is steadily increasing for a variety of reasons, it is a very safe
      intervention particularly when compared to conventional treatment and its lack of
      serious side effects might in part account for some of its popularity. The
      science behind acupuncture is also explored in terms of its underlying mechanisms
      and includes pain gate, endogenous opioids, diffuse noxious inhibitory control,
      serotonin and bioelectricity as possible explanations. The efficacy of
      acupuncture for a range of chronic musculoskeletal conditions is then explored
      and it is concluded that acupuncture has a place in the treatment of chronic
      musculoskeletal pain and in particular osteo-arthritis (OA). Where degenerative
      conditions are involved, acupuncture clearly cannot provide a 'cure' but can
      provide symptomatic relief, often over a prolonged period.

PMID- 17004406
TI  - Freedom of information: a case study.
AB  - The purpose of this case study was to find out how easy it was to access
      information on the hygiene standards of eating places open to the public. Using
      the Freedom of Information (FOI) Act 2000, four adjacent local authorities in
      South Wales were asked to provide the last food hygiene report of an eating place
      in their area. The disclosed reports were assessed to determine how useful they
      would be to an individual seeking more information on a food premise. It was
      relatively easy to obtain information from two authorities and difficult if not
      impossible with the others. One local authority refused to release information
      despite the intervention of the FOI Commissioner. The quality of the information
      released was variable. This ranged from a completed comprehensive inspection
      protocol to a hand-written, illegible, incomplete report that failed to
      adequately differentiate between requirements and recommendations. Without some
      training in food law and food hygiene it would be difficult to interpret the
      reports. There was no evidence from the information provided of inspection
      scoring. The case study raises concerns about the effectiveness of the Act for
      consumers who wish to obtain information about the hygiene standards of food
      premises. While the specialist information provided by hygiene inspection reports
      may be useful to businesses it is not helpful for the lay public. Consumers must
      be prepared to exercise patience and tenacity if they want this information.
      Concerns must be raised about the consistency of the inspection process and about
      the willingness of some local authorities to be transparent about the inspection
      and enforcement process.

PMID- 17004407
TI  - Best practice in smoking cessation services for pregnant women: results of a
      survey of three services reporting the highest national returns, and three beacon
      services.
AB  - AIMS: The NHS allocated dedicated funds to establish specialist smoking cessation
      services for pregnant smokers in England in 2000. An early survey revealed some
      uncertainty as to how the new services should work and monitor their outcome. The
      current survey focused on identifying examples of good practice in this difficult
      new field. METHOD: Three services with the highest number of successful four-week
      quitters reported for the 2003/4 monitoring year were identified from Department
      of Health (DH) monitoring records, and three services were nominated from those
      known in the field as examples of best practice. There was no overlap between the
      two groups. All six services provided in-depth interviews. RESULTS: All three
      highest ranking services that reported close to 100 per cent success rates
      included unaided quitters identified from hospital wards, rather then smokers
      actually treated. They had only minimal or average genuine treatment provision
      for pregnant smokers in place. The three beacon services far exceeded the
      national throughput and outcome average identified in the previous survey, and
      provided a wealth of useful information. Although they differed in staffing
      levels and other aspects of their activities, they all shared several key
      elements, including a systematic training of midwives in how to refer pregnant
      smokers, offering nicotine replacement treatment to almost all clients and having
      an efficient system of providing the prescriptions, offering flexible home
      visits, and providing intensive multi-session treatment delivered by a small
      number of dedicated staff. CONCLUSION: Smoking cessation services for pregnant
      women may need clearer guidance on what they are expected to provide, and how
      they should monitor their outcome. The key features of the beacon services can
      serve as a practical model of current best practice applicable across most PCTs.

PMID- 17004408
TI  - Tinnitus in an active duty navy diver: A review of inner ear barotrauma,
      tinnitus, and its treatment.
AB  - This case elucidates subtle cues that must be appreciated by the examiner in
      diving related injuries, who may not have experience with barotrauma-mediated
      pathology. Inner-ear barotrauma (IEBT) does not mandate ostensible hearing loss
      or vertigo; tinnitus may be the sole manifestation. Symptoms may present hours or
      even days post-dive. A common misconception exists that there are no efficacious
      treatment options for IEBT short of surgery for an overt perilymphatic fistula.
      Treatment options are available including acute high dose steroid administration,
      as prescribed for acute noise-induced or idiopathic hearing loss, optimally
      administered within three weeks of the acute insult. Tinnitus does not
      necessarily constitute a chronic untreatable symptom, which the patient must
      learn "to live with".

PMID- 17004409
TI  - Indication for hyperbaric oxygen treatment as a predictor of tympanostomy tube
      placement.
AB  - INTRODUCTION: Hyperbaric oxygen therapy (HBO2) has been utilized for many years
      for a multitude of disease entities. One commonly encountered side-effect is otic
      barotrauma. OBJECTIVE: To determine if patients with specific disease processes
      are at increased risk of requiring tympanostomy tubes during HBO2. METHODS: Data
      was obtained from Jan. 2000 to Dec. 2004, retrospectively. The requirement for
      tympanostomy tubes during a course of HBO2 was established. RESULTS: 325 met
      inclusion criteria. Fifteen percent of patients overall (95% CI= 11-19%) required
      tympanostomy tubes. Tubes were required in: 5% necrotizing soft tissue infection
      (p=0.33); 10% failed/threatened graft (p=0.39); 15% problem wounds; 17% chronic
      refractory osteomyelitis (CRO) (p=0.64); 22% soft tissue radionecrosis
      (STRN)/osteoradionecrosis (ORN) (p=0.02); 33% of crush injuries (p=0.10). Twenty
      nine percent of nasopharyngeal radiation injury patients (p=0.001) and 10% of the
      non-nasopharyngeal radiation patients (p=0.36) received tympanostomy tubes.
      CONCLUSION: A significant increase in tympanostomy tubes were required in
      nasopharyngeal radiation injury patients.

PMID- 17004410
TI  - Side effects of hyperbaric oxygen therapy in children with cerebral palsy.
AB  - BACKGROUND: This article reports the side effects observed in a double-blind
      placebo-controlled multi-center randomized clinical trial carried out to assess
      the efficacy and safety of hyperbaric oxygen (HBO2) therapy in children with
      cerebral palsy. Intention-to-treat analysis did not prove to have a beneficial
      effect. MATERIAL AND METHODS: 111 children aged 3 to 12 years were included and
      followed for 8 weeks. They all received 40 compressions of 1 hour (5 days per
      week). In the treated group (n=57), HBO2 sessions consisted of an exposure to
      100% oxygen at 1.75 atmosphere absolute (atm abs) while children in the control
      group (n=54) received air at 1.3 atm abs. A physician carried out a general
      health surveillance including an ear examination prior to and immediately
      following each session. All clinical events occurring during the course of the
      study were recorded. FINDINGS: Events were classified in 3 categories: Events
      related to pressure/volume changes, events related to oxygen toxicity, and other
      events. No events due to oxygen toxicity were noted. Only middle ear barotrauma
      significantly differed according to the groups (50% in HBO2 session group versus
      27.8% in control group). Other events were rare and equivalent in both groups.
      CONCLUSION: Short-term exposure to HBO2 at medium level pressure (1.75 atm abs)
      was responsible for a significant increase of middle ear barotrauma compared to
      children that received very low external pressure (1.3 atm abs).

PMID- 17004411
TI  - Basal ganglia volumes following CO poisoning: A prospective longitudinal study.
AB  - Carbon monoxide (CO) poisoning may result in focal and diffuse neuropathological
      changes, including basal ganglia lesions. The effect of CO poisoning on basal
      ganglia volumes over time is unclear. We assessed basal ganglia volumes
      longitudinally following CO poisoning. We prospectively enrolled 73 CO poisoned
      patients who underwent brain MR imaging on day 1 (baseline), 2 weeks, and 6
      months post-CO poisoning. Basal ganglia volumes were obtained. One patient had
      bilateral globus pallidus lesions at two weeks and 6 months. Of the CO-poisoned
      patients 28% had volume reduction in at least one basal ganglia structure by 6
      months, of which 21% had putamen, 15% had caudate, 15% had globus pallidus, and
      16% had total basal ganglia volume reduction. Putamen volumes were significantly
      smaller from baseline to six months (p = 0.02). Verbal memory and mental
      processing speed correlated with smaller putamen and globus pallidus volumes.
      Carbon monoxide poisoning results in basal ganglia volume reduction 6 months post
      CO poisoning. Slow mental processing speed and impaired memory correlated with
      smaller putamen and globus pallidus volumes. Clinicians need to be aware of basal
      ganglia neuropathologic changes in the absence of observable lesions following CO
      poisoning.

PMID- 17004413
TI  - Dissociation of neurological deficits in spinal decompression illness.
AB  - Functional differentiation is found in the spinal cord. A unique set of
      neurological deficits follows a multi-focal injury. Clinically, sensory and motor
      disturbance present independently, often resulting in sensory and motor deficit
      dissociation. This study examined 103 spinal decompression illness (DCI) cases.
      The neurological deficit dissociation was classified as follows: 1) Cases with
      sensory impairment only, or motor dysfunction alone, were tagged as having
      "dissociation" (44 cases); when a case was with both sensory and motor
      dysfunction, the spinal level of the sensory impairment was determined and was
      matched with the spinal segments responsible for the motor dysfunction; 2) If the
      two spinal areas did not match (i.e. with no regional overlap), they were tagged
      as having "dissociation" for each motor dysfunction (32 cases). In total,
      dissociation was present in 76 out of 103 cases. We concluded that clinical
      neurological deficit dissociation is frequently observed in spinal DCI.

PMID- 17004412
TI  - Storm-related carbon monoxide poisoning: lessons learned from recent epidemics.
AB  - Over the past 15 years, a number of epidemics of carbon monoxide (CO) poisoning
      related to various storms have been reported. While the geographical location of
      these outbreaks and the types of storms involved has been diverse, review of the
      events reveals a number of common factors and themes. This paper summarizes the
      details of 9 published reports describing CO poisoning associated with 11
      different storms. When common patterns were examined, five "lessons to be
      learned" from the experience were derived. They are (1) loss of electrical power
      can lead indirectly to carbon monoxide poisoning, (2) campaigns to educate the
      public about risks for CO exposure should be timed regionally to coincide with
      the peak risk for typical storms, (3) significant opportunities exist for
      prevention of generator-related CO poisoning, (4) there is a window of time for
      effective communications regarding the dangers of CO poisoning even after a storm
      strikes, and (5) the major sources of CO responsible for poisonings can be
      related to the type of storm and are predictable. It is hoped that each of these
      lessons are used to develop public programs designed to prevent storm-associated
      CO poisoning in the future.

PMID- 17004414
TI  - NIHSS applied to cerebral neurological dive injuries as a tool for dive injury
      severity stratification.
AB  - BACKGROUND: Evaluation via National Institutes of Health Stroke Scale (NIHSS)
      upon presentation in hospital triage following ischemic stroke is predictive of
      recovery or progression to neurological deficits. Cerebral injuries sustained
      while diving have symptoms similar to stroke. Applying the NIHSS to dive injuries
      may successfully summarize neurological dive injuries, providing a standardized
      tool for study of dive injury data. METHODS: We retrospectively determined NIHSS
      scores for a diverse population of 192 divers presenting to the University of
      Hawaii recompression chamber from 1983-2002, both prior to initial treatment and
      after all treatment. Spinal and vestibular decompression sickness cases were
      excluded. RESULTS: The performance of the NIHSS among this diving population was
      similar to its performance as an accepted tool in evaluation of ischemic stroke,
      although results are influenced by the abundance of mild injury cases in the data
      set. The estimated C-statistic with NIHSS predicting no observable deficit was
      0.88, and predicting post NIHSS of 0-1 was 0.85 (vs. 0.86 when applied to
      stroke). Sensitivity for predicting recovery (NIHSS 0-1) at discharge was 0.99
      (vs. 0.97 for stroke). CONCLUSIONS: The NIHSS applied to cerebral dive injuries
      has adequate predictive ability and correlates with other measures of dive
      injuries, while providing a standardized, more graduated scale. The NIHSS may be
      useful as a standardized measurement for evaluation of treatment regimens and
      adjunctive therapy for diving injuries.

PMID- 17004416
TI  - Metabolic production of carbon dioxide in simulated sea states: relevance for
      hyperbaric escape systems.
AB  - Hyperbaric Escape Systems (HES) are used when saturation diving bells have to be
      evacuated and divers transported to safety. The aim of the present investigation
      was to determine the levels of metabolic CO2 production expected from the
      occupants of an HES in different wave states, and from this, to recommend a
      reasonable and safe requirement for scrubbing CO2 within an HES. The CO2
      production and heart rate of 20 male subjects representing saturation divers were
      collected while they were seated in an HES seat, fixed to an inflatable rescue
      vessel. The vessel was tethered in a wave pool and longitudinal (L),
      perpendicular (P), and calm (C) sea conditions were reproduced. Heart rate did
      not differ between conditions (P=0.33) the mean (SD) heart rates (b x min(-1))
      were: C: 71 (8.5); L: 74 (9); P: 75 (9). Carbon dioxide production was
      significantly higher (P=0.005) with the boat orientated perpendicular to the
      waves compared to the calm condition. The mean (plus 99% confidence interval)
      carbon dioxide production for each of the conditions was C = 319mL x min(-1) +
      (41mL x min(-1)) = maximum of 360mL x min(-1); L=374mL x min(-1) + (46mL x min(
      1)) = maximum of 420mL x min(-1); P = 409mL x min(-1) + (57mL x min(-1)) =
      maximum of 466mL x min(-1). It is therefore recommended that a 12 person HES
      should be capable of scrubbing at least 8,053L of carbon dioxide in 24 hours.
      Thus, the current requirement for 8,415L in 24h is reasonable.

PMID- 17004415
TI  - The effect of endurance training on the rate of nitrogen elimination in women.
AB  - INTRODUCTION: The rate of nitrogen elimination may be an important factor in
      evaluating the risk of DCS following dives. The present study determined the
      reproducibility of a method for evaluating nitrogen elimination (series I), and
      the effect of chronic training on the nitrogen elimination in healthy young women
      (series II). METHODS: Nitrogen elimination was determined with subjects wearing
      an AGA full-face mask breathing pure oxygen. To evaluate the reproducibility of
      the method for nitrogen elimination, three tests were performed in six subjects
      in series I. Nitrogen elimination in series II was measured before and after the
      training period. The training protocol (series II) consisted of interval
      training, three times per week for eight weeks. Four repeated intervals
      alternated between four minutes at 90-95% of maximum heart rate and three minutes
      at 50-60%. RESULTS: There was no significant difference between the three
      repeated tests. Interval training for eight weeks increased maximum oxygen uptake
      by 22.1%. Endurance training did not influence the total nitrogen elimination at
      rest. CONCLUSION: The method for evaluating nitrogen elimination at rest was
      found to be reproducible. Improved aerobic capacity does not increase the rate of
      nitrogen elimination at rest.

PMID- 17004417
TI  - The effects of hyperbaric oxygen treatment on lipid peroxidation of pregnant
      rabbits and their fetus during late pregnancy.
AB  - OBJECTIVE: To measure the effects of hyperbaric oxygen on lipid peroxidation of
      pregnant and fetal rabbits during late pregnancy. METHODS: Sixteen pregnant
      rabbits were randomly and equally divided into two groups. One, the HBO2 group,
      was exposed to 2-atm oxygen for 60 min a day from the 21st to the 30th day of
      gestation, and the other group, non-HBO2 group, did not obtain any hyperbaric
      oxygen treatment. RESULTS: On the 30th day of pregnant period, the activity of
      antioxidant enzyme SOD in plasma of the pregnant rabbits of the HBO2 group was
      significantly higher than that of the non-HBO2 group, but there was no
      significant difference in the level of oxidative stress marker 8-iso-PG-F2 alpha
      between the two groups. As for the fetal rabbits, the SOD activity in umbilical
      plasma, placenta tissue and fetal brain tissue of HBO2 group was significantly
      higher than that of the non-HBO2 group, while there was no statistical difference
      between the concentrations of 8-iso-PG-F2 alpha of HBO2 and non-HBO2 group.
      CONCLUSION: HBO2 treatment during the late pregnancy up-regulates the activity of
      antioxidant enzyme in plasma of pregnant rabbits, placenta, umbilical plasma, and
      fetal brain. This does not have significant effect on the oxidative stress in
      these tissues.

PMID- 17004418
TI  - Hyperbaric oxygen therapy: a high-risk procedure? An update.

PMID- 17004419
TI  - The importance of the African-American church and spirituality in the lives of
      the African-American community.

PMID- 17004420
TI  - Spirituality of African-American women: correlations to health-promoting
      behaviors.
AB  - The purpose of this study was to investigate how spirituality relates to health
      promoting behaviors in African-American women. Using Burkhart's theoretical
      framework for spirituality, a descriptive cross-sectional correlational design
      was used. A group of 260 (N=260) women completed Rosenbergh's Self-Esteem Scale,
      the Health Promoting Lifestyle Profile II, the Spiritual Perspective Scale, the
      Brief Block 2000 Food Frequency Questionnaire (FFQ). These women also provided
      the researchers with their socio-demographic data. Canonical correlation analysis
      identified a significant pair of canonical variables which indicated that those
      individuals with good nutrition (.95), physical activity (.79), and healthy
      eating (.42) were positively associated with stress management (.88), health
      responsibility (.67), spiritual growth (.66), interpersonal relations (.50),
      education (.49), and self-esteem (.33). This set of variables explained 56% of
      the variability (p < .001). Practitioners should incorporate the message of
      spirituality by focusing on strategies to improve health responsibility,
      interpersonal relations, and self-esteem, along with health-promoting behaviors.

PMID- 17004421
TI  - African-American women, metabolic syndrome, and national cholesterol education
      program criteria: a pilot study.
AB  - BACKGROUND: The association between elevated levels of triglycerides and insulin
      may be weaker in African-American women than in women of other groups, leading to
      underdiagnosis of the metabolic syndrome (MetS) in African-American women when
      using the National Cholesterol Education Program (NCEP) criteria, as that
      criteria does not include a marker of insulin resistance, using elevated
      triglycerides to provide an indirect indication of insulin resistance.
      OBJECTIVES: To determine the degree of agreement between two definitions for the
      MetS, that described by the NCEP and the NCEP criteria with the addition of a
      marker of insulin resistance in a sample of African-American women. METHOD: This
      nonexperimental pilot study took place in the General Clinical Research Center of
      a major medical center Thirty-three African-American women 19-45 years of age
      were screened using the NCEP criteria for MetS, additional markers of insulin
      resistance, and a 2-hour Oral Glucose Tolerance Test. FINDINGS: Six (18%) women
      were classified as having the MetS using the NCEP criteria. When one of three
      markers for insulin resistance (hyperinsulinemia, acanthosis nirgricans, or
      Homeostatic Model Assessment Insulin Resistance) was added to the criteria, 15
      (45.5%) to 19 (59.5%) of the women were then identified as having MetS.
      DISCUSSION: As identified in the literature, the prevalence of cardiovascular
      disease risk in African-American women may be underestimated based on the sole
      use of the NCEP criteria. Further because there is some evidence that insulin
      resistance develops before many other indicators, the addition of a marker of
      insulin resistance may assist in earlier identification of African-American women
      at high risk for cardiovascular disease.

PMID- 17004422
TI  - Exercise, self-efficacy, and exercise behavior in hypertensive older African
      Americans.
AB  - Older African-Americans have very high rates of hypertension, and they experience
      one of the highest hypertension-related death rates of all American ethnic
      groups. They are also one of the most physically inactive groups, which
      contributes to their hypertension-related health problems. Interventions are
      needed to assist them in increasing their exercise activities and thereby gaining
      better hypertension control. This study evaluated the relationship between
      physical activity level and exercise self-efficacy for this group. Findings
      support a strong association and suggest that interventions that address exercise
      self-efficacy would be helpful for increasing the level of exercise in older
      African-Americans. Suggested nursing interventions, based on theory, are
      proposed.

PMID- 17004423
TI  - Risky sexual behaviors of adolescents in rural Malawi: evidence from focus
      groups.
AB  - Little is known about rural Malawian adolescents' perceptions of their sexual
      behavior and what would constitute an effective HIV risk-reduction program. This
      study explored the perceptions of Malawain adolescents using qualitative
      description research with focus groups. A purposive sample of 144 adolescents,
      ranging from 10 to 19 years of age was obtained. Subjects were then placed in
      focus groups separated by gender Qualitative content analysis revealed that
      adolescents were at risk for HIV based on the select behaviors These included
      early sexual debut, multiple partners, non-use of condoms and among girls older
      partners These adolescents acknowledged peer pressure and lack of parental
      supervision as factors that perpetuated these behaviors and identified two
      components of HIV prevention programs. For example, parental involvement and
      support for sexual abstinence were among the issues discussed. It is essential
      that HIV risk-reduction programs create ways of involving parents and of
      enhancing adolescents' HIV risk-reduction skills by helping them to change peer
      norms and to develop negotiation and assertiveness skills to in order to resist
      peer pressure.

PMID- 17004424
TI  - Variations in the experiences and expressions of depression among ethnic
      minorities.
AB  - The purpose of this paper is to examine the ethnic differences in the experiences
      and expressions of depressive symptoms. Also, a discussion is presented regarding
      the effects that depression has on the individual and consequently the adverse
      impact it will have on society. Because the expressions of depression are so
      varied, appropriate measures are required to account for the differences of these
      expressions in individuals in order to facilitate appropriate diagnosing Both in
      the United States and throughout the world, depression accounts for a significant
      proportion of psychiatric disorders, with women and the poor experiencing a
      disproportionate burden of morbidity. It is essential to remember that clinical
      depression is never normal and should not be accepted as a normal part of life
      for any individual, regardless of race, age, or life situation. Depression is a
      chronic, often relapsing illness, especially if initially under-treated. With
      depression, it is also essential to identify the role that certain biological
      variations and particularly the role that ethnicity and gender may play. In other
      words, because of environmental and certain biological variations, there may be
      diferences in not only the life experiences but also the mode of expression that
      depression takes, particularly in women and ethnic people of color. It is
      essential to identify these significant differences. Certainly, minimizing the
      risk of psychiatric misdiagnosis is critical to achieving optimal health.

PMID- 17004425
TI  - Resilience in homeless adults: a review of literature.
AB  - Although the concept of resilience has been studied for the past three decades, a
      paucity of research has focused on this concept in homeless adults, particularly
      among homeless adults who are persons of color African-Americans have been
      characterized as being resilient and it has been reported that African-Americans
      are disproportionately represented among the homeless population nationwide. The
      purpose of this article is to review the scope of research previously done in the
      area of resilience in homeless adults and to highlight the importance of the
      concept of resilience in the lives and existence of this at-risk group. Homeless
      adults face enormous stressors on a daily basis as they navigate a minefield of
      mental, physical, and environmental risks. How they respond and how they adapt to
      these stressors can potentially affect their health outcomes as well as their
      quality of life. The seven articles retrieved for this article support the
      contention that further research is needed to increase the understanding of how
      the concept of resilience impacts the ability of homeless adults, and in
      particular persons of color to endure and survive despite their adverse
      conditions.

PMID- 17004426
TI  - Factors associated with delays in screening of self-detected breast changes in
      African-American women.
AB  - Breast cancer mortality is higher among African-American women than among White
      women. African-American women are 25% more likely to present with late stage
      breast cancer and 20% more likely to die from breast cancer than White women.
      Treatment delay of 3 months is a significant factor in breast cancer mortality
      The purpose of this integrative review is to explore factors that impact delays
      in screening The most common patient-controlled delays were lack of education and
      knowledge about the perceived seriousness of breast symptoms, the associated risk
      factors, limited knowledge regarding the potential benefits of early detection in
      improving breast cancer survival, and expressed fatalistic perspectives about
      breast cancer. Other variables related to delays included factors such as
      advancing age, low socioeconomic status, fear of diagnosis, consequences of
      cancer treatments, shame and embarrassment, misconceptions about the etiology of
      breast cancer, family priorites, denial, and spirituality including faith
      influenced delays.

PMID- 17004427
TI  - Heart smart.

PMID- 17004428
TI  - Employees are key.

PMID- 17004429
TI  - The price is right.

PMID- 17004430
TI  - Focus on the crucial between-encounter periods with patient experience mapping.

PMID- 17004431
TI  - Sound effects.

PMID- 17004432
TI  - Selling short.

PMID- 17004433
TI  - Close the gap.

PMID- 17004434
TI  - The play's the thing.

PMID- 17004435
TI  - Board and CEO critical.

PMID- 17004436
TI  - Identifying trends.

PMID- 17004437
TI  - Be a pepper.

PMID- 17004441
TI  - Reply to comment on "Auditory-nerve first-spike latency and auditory absolute
      threshold: a computer model".
AB  - Krisha [J. Acoust. Soc. Am., in press (2006)] has commented that an explanation
      based on presynaptic calcium accumulation at the inner hair cell is an incorrect
      explanation for the success of a model of the auditory periphery [Meddis, R., J.
      Acoustic. Soc. Am. 119, 406-417 (2006)] in explaining data on first-spike
      auditory nerve latency. This reply accepts the criticism and accepts the strength
      of an alternative explanation based on expected latencies in random sequences of
      low-probability events. This reply also goes on briefly to explore the
      application of this argument to other phenomena, including the dependence of
      absolute auditory threshold on the duration of the stimulus. This has wide
      ranging implications for the concept of "temporal integration" in psychophysics.

PMID- 17004443
TI  - Coupled integral equations for sound propagation above a hard ground surface with
      trench cuttings.
AB  - A set of coupled integral equations is formulated for the investigation of sound
      propagation from an infinitesimal harmonic line source above a hard ground
      surface corrugated with cuttings. Two half-space Green's functions are employed
      in the formulation. The first one defined for the upper half space is used to
      reduce the problem size and eliminate the edge effect resulting from the boundary
      truncation; the other one for the lower half space is to simplify the
      representation of the Neumann-Dirichlet map. As a result, the unknowns are only
      distributed over the corrugated part of the surface, which leads to substantial
      reduction in the size of the final linear system. The computational complexity of
      the Neumann-Dirichlet map is also reduced. The method is used to analyze the
      behavior of sound propagation above textured surfaces the impedance of which is
      expectedly altered. The effects of number and opening of trench cuttings, and the
      effect of source height are investigated. The conclusions drawn can be used for
      reference in a practical problem of mitigating gun blast noise.

PMID- 17004451
TI  - Internal wave effects on the ambient noise notch in the East China Sea:
      model/data comparison.
AB  - The vertical directivity pattern of the ambient noise field observed in shallow
      water is typically anisotropic with a trough in the horizontal. This trough,
      often called the ambient noise notch, develops because downward refraction
      steepens all rays emanating from near the sea surface. Variability in the
      environment has the potential to redistribute the noise into shallower angles and
      thereby fill the notch. In the present work, a model for the width and depth of
      the ambient noise notch is developed. Transport theory for acoustic propagation
      is combined with a shallow water internal wave model to predict the average
      output of a beamformer. Ambient noise data from the East China Sea are analyzed
      in the 1-to-5-kHz band. Good agreement between the model and the data for both
      the width and depth of the ambient noise notch is obtained at multiple
      frequencies, suggesting that internal wave effects are significant.

PMID- 17004458
TI  - Feeding behavior of wild dugongs monitored by a passive acoustical method.
AB  - Little is known about feeding behavior of wild dugongs (Dugong dugon) because
      direct measurements of feeding events in the water were scarcely feasible. In
      this study, the authors achieved the first successful feeding sound monitoring in
      a seagrass area using a full-band underwater recording system (called automatic
      underwater sound monitoring system for dugong: AUSOMS-D). In total, 175 feeding
      sounds were identified in 205 h of recording. Feeding sounds were only detected
      at night, implying diurnal differences in the feeding behavior of the studied
      dugong population. Differences in periodicity of feeding sounds suggested that
      two or more individuals were in the acoustically observable area. Furthermore, a
      feeding position monitored by two AUSOMS-Ds was used to calculate source levels
      of dugong feeding sounds. Assuming spherical_propagation, source levels were
      measured between 70.6 and 79.0 dB rms re 1 microPa/square root of Hz.

PMID- 17004459
TI  - Estimated detection distance of a baiji's (Chinese river dolphin, Lipotes
      vexillifer) whistles using a passive acoustic survey method.
AB  - Source levels and phonation intervals of whistles produced by a free-ranging
      baiji (Chinese river dolphin) were measured in the seminatural reserve of Shishou
      in Hubei, China. A total of 43 whistles were recorded over 12 recording sessions.
      The mean dominant frequency (the frequency at the highest energy) was 5.7 kHz
      (s.d. = 0.67). The calculated source level was 143.2 dB rms re 1 microPa (s.d. =
      5.8). Most phonation intervals were shorter than 460 s, and the average interval
      was 205 s (s.d. = 254). Theoretical detection range of baiji's whistle was 6600 m
      at the present study site, but it could reduce a couple of hundred meters in
      practical noisy situation in the Yangtze River. Sporadic phonation (205 s
      interval on average) with relatively faint signal of baiji was considered to be
      difficult to be detected by a towing hydrophone system. Stationed monitoring or
      slow speed towing of hydrophones along the river current is recommended.

PMID- 17004464
TI  - Analysis of Sabine and Eyring equations and their application to concert hall
      audience and chair absorption.
AB  - Historically, two equations have been used for predicting reverberation times,
      Sabine and Eyring. A precise means is presented for determining Eyring absorption
      coefficients alpha(eyring) when the Sabine coefficients alpha(sabine) are known,
      and vice versa. Thus, either formula can be used provided the absorption
      coefficients for the Sabine formula are allowed to exceed 1.0. The Sabine formula
      is not an approximation to the Eyring equation and is not a shortcoming. Given
      low reverberation times, the ratio of alpha(sabine) to alpha(eyring) may become
      greater than 2.0. It is vital that, for correct prediction of reverberation
      times, the absorption coefficients used in either formula must have been
      determined in spaces similar in size and shape, with similar locations of high
      absorption (audience) areas, and with similar reverberation times. For concert
      halls, it is found that, when the audience area (fully occupied) and midfrequency
      reverberation time are postulated, the hall volume is directly proportional to
      the audience absorption coefficient. Approximately 6% greater room volumes are
      needed when choosing nonrectangular versus classical-rectangular shaped halls and
      approximately 10% greater volumes when choosing heavily upholstered versus medium
      upholstered chairs. Determinations of audience sound absorption coefficients are
      presented, based on published acoustical and architectural data for 20 halls.

PMID- 17004467
TI  - Predictions of formant-frequency discrimination in noise based on model auditory
      nerve responses.
AB  - To better understand how the auditory system extracts speech signals in the
      presence of noise, discrimination thresholds for the second formant frequency
      were predicted with simulations of auditory-nerve responses. These predictions
      employed either average-rate information or combined rate and timing information,
      and either populations of model fibers tuned across a wide range of frequencies
      or a subset of fibers tuned to a restricted frequency range. In general, combined
      temporal and rate information for a small population of model fibers tuned near
      the formant frequency was most successful in replicating the trends reported in
      behavioral data for formant-frequency discrimination. To explore the nature of
      the temporal information that contributed to these results, predictions based on
      model auditory-nerve responses were compared to predictions based on the average
      rates of a population of cross-frequency coincidence detectors. These comparisons
      suggested that average response rate (count) of cross-frequency coincidence
      detectors did not effectively extract important temporal information from the
      auditory-nerve population response. Thus, the relative timing of action
      potentials across auditory-nerve fibers tuned to different frequencies was not
      the aspect of the temporal information that produced the trends in formant
      frequency discrimination thresholds.

PMID- 17004468
TI  - Modeling auditory-nerve responses for high sound pressure levels in the normal
      and impaired auditory periphery.
AB  - This paper presents a computational model to simulate normal and impaired
      auditory-nerve (AN) fiber responses in cats. The model responses match
      physiological data over a wider dynamic range than previous auditory models. This
      is achieved by providing two modes of basilar membrane excitation to the inner
      hair cell (IHC) rather than one. The two modes are generated by two parallel
      filters, component 1 (C1) and component 2 (C2), and the outputs are subsequently
      transduced by two separate functions. The responses are then added and passed
      through the IHC low-pass filter followed by the IHC-AN synapse model and
      discharge generator. The C1 filter is a narrow-band, chirp filter with the gain
      and bandwidth controlled by a nonlinear feed-forward control path. This filter is
      responsible for low and moderate level responses. A linear, static, and broadly
      tuned C2 filter followed by a nonlinear, inverted and nonrectifying C2
      transduction function is critical for producing transition region and high-level
      effects. Consistent with Kiang's two-factor cancellation hypothesis, the
      interaction between the two paths produces effects such as the C1/C2 transition
      and peak splitting in the period histogram. The model responses are consistent
      with a wide range of physiological data from both normal and impaired ears for
      stimuli presented at levels spanning the dynamic range of hearing.

PMID- 17004469
TI  - Temporal integration of the contralateral acoustic-reflex threshold and its age
      related changes.
AB  - Although numerous studies have investigated temporal integration of the acoustic
      reflex threshold (ART), research is lacking on the effect of age on temporal
      integration of the ART. Therefore the effect of age on temporal integration of
      the ART was investigated for a broad-band noise (BBN) activator. Subjects
      consisted of two groups of adults with normal-hearing sensitivity: one group of
      20 young adults (ten males and ten females, ages 18-29 years, with a mean age of
      24 years) and one group of 20 older adults (ten males and ten females, ages 59-75
      years, with a mean age of 67.5 years). Activating stimulus durations were 12, 25,
      50, 100, 200, 300, 500, and 1000 ms. Significant main effects for duration and
      age were obtained. That is, as the duration increased, the acoustic reflex
      threshold for BBN decreased. The interactions of duration x age group and
      duration x hearing level were not significant. The result of pair-wise analysis
      indicated statistically significant differences between the two age groups at
      durations of 20 ms and longer. The observed age effect on temporal integration of
      the ART for the BBN activator is interpreted in relation to senescent changes in
      the auditory system.

PMID- 17004471
TI  - Detection and F0 discrimination of harmonic complex tones in the presence of
      competing tones or noise.
AB  - Normal-hearing listeners' ability to "hear out" the pitch of a target harmonic
      complex tone (HCT) was tested with simultaneous HCT or noise maskers, all
      bandpass-filtered into the same spectral region (1200-3600 Hz). Target-to-masker
      ratios (TMRs) necessary to discriminate fixed fundamental-frequency (F0)
      differences were measured for target F0s between 100 and 400 Hz. At high F0s (400
      Hz), asynchronous gating of masker and signal, presenting the masker in a
      different F0 range, and reducing the F0 rove of the masker, all resulted in
      improved performance. At the low F0s (100 Hz), none of these manipulations
      improved performance significantly. The findings are generally consistent with
      the idea that the ability to segregate sounds based on cues such as F0
      differences and onset/offset asynchronies can be strongly limited by peripheral
      harmonic resolvability. However, some cases were observed where perceptual
      segregation appeared possible, even when no peripherally resolved harmonics were
      present in the mixture of target and masker. A final experiment, comparing TMRs
      necessary for detection and F0 discrimination, showed that F0 discrimination of
      the target was possible with noise maskers at only a few decibels above detection
      threshold, whereas similar performance with HCT maskers was only possible 15-25
      dB above detection threshold.

PMID- 17004470
TI  - Comparison of the roex and gammachirp filters as representations of the auditory
      filter.
AB  - Although the rounded-exponential (roex) filter has been successfully used to
      represent the magnitude response of the auditory filter, recent studies with the
      roex(p, w, t) filter reveal two serious problems: the fits to notched-noise
      masking data are somewhat unstable unless the filter is reduced to a physically
      unrealizable form, and there is no time-domain version of the roex(p, w, t)
      filter to support modeling of the perception of complex sounds. This paper
      describes a compressive gammachirp (cGC) filter with the same architecture as the
      roex(p, w, t) which can be implemented in the time domain. The gain and asymmetry
      of this parallel cGC filter are shown to be comparable to those of the roex(p, w,
      t) filter, but the fits to masking data are still somewhat unstable. The roex(p,
      w, t) and parallel cGC filters were also compared with the cascade cGC filter
      [Patterson et al., J. Acoust. Soc. Am. 114, 1529-1542 (2003)], which was found to
      provide an equivalent fit with 25% fewer coefficients. Moreover, the fits were
      stable. The advantage of the cascade cGC filter appears to derive from its
      parsimonious representation of the high-frequency side of the filter. It is
      concluded that cGC filters offer better prospects than roex filters for the
      representation of the auditory filter.

PMID- 17004472
TI  - The influence of spatial separation on divided listening.
AB  - If spatial attention acts like a "spotlight," focusing on one location and
      excluding others, it may be advantageous to have all targets of interest within
      the same spatial region. This hypothesis was explored using a task where
      listeners reported keywords from two simultaneous talkers. In Experiment 1, the
      two talkers were placed symmetrically about the frontal midline with various
      angular separations. While there was a small performance improvement for moderate
      separations, the improvement decreased for larger separations. However, the
      dependency of the relative talker intensities on spatial configuration accounted
      for these effects. Experiment 2 tested whether spatial separation improved the
      intelligibility of each source, an effect that could counteract any degradation
      in performance as sources fell outside the spatial spotlight of attention. In
      this experiment, intelligibility of individual sources was equalized across
      configurations by adding masking noise. Under these conditions, the cost of
      divided listening (the drop in performance when reporting both messages compared
      to reporting just one) was smaller when the spatial separation was small. These
      results suggest that spatial separation enhances the intelligibility of
      individual sources in a competing pair but increases the cost associated with
      having to process both sources simultaneously, consistent with the attentional
      spotlight hypothesis.

PMID- 17004473
TI  - Middle ear cavity and ear canal pressure-driven stapes velocity responses in
      human cadaveric temporal bones.
AB  - Drive pressure to stapes velocity (V(st)) transfer function measurements are
      collected and compared for human cadaveric temporal bones with the drive pressure
      alternately on the ear canal (EC) and middle ear cavity (MEC) sides of the
      tympanic membrane (TM), in order to predict the performance of proposed middle
      ear implantable acoustic hearing aids, as well as provide additional data for
      examining human middle ear mechanics. The chief finding is that, in terms of the
      V(st) response, MEC stimulation performs at least as well as EC stimulation below
      8 kHz, provided that the EC is unplugged. Plugging the EC causes a reduced
      response for MEC drive below 2 kHz, due to a corresponding reduction of the
      pressure difference between the two sides of the TM. Between 8 and 11 kHz, the
      MEC drive transfer functions feature an approximately 17 dB drop in magnitude
      below the EC drive case, the cause of which remains unknown. The EC drive
      transfer functions reported here feature significantly less magnitude roll-off
      above 1 kHz than previous studies [with a slope of -2.3 vs -6.7 dB/octave for
      Aibara et al., Hear. Res. 152, 100-109 (2001)], and significantly more phase
      group delay (134 vs 62 micros for Aibara et al.).

PMID- 17004474
TI  - Auditory filters and the benefit measured from spectral enhancement.
AB  - Algorithms designed to improve speech intelligibility for those with
      sensorineural hearing loss (SNHL) by enhancing peaks in a spectrum have had
      limited success. Since testing of such algorithms cannot separate the theory of
      the design from the implementation itself, the contribution of each of these
      potentially limiting factors is not clear. Therefore, psychophysical paradigms
      were used to test subjects with either normal hearing or SNHL in detection tasks
      using well controlled stimuli to predict and assess the limits in performance
      gain from a spectrally enhancing algorithm. A group of normal-hearing (NH) and
      hearing-impaired (HI) subjects listened in two experiments: auditory filter
      measurements and detection of incremented harmonics in a harmonic spectrum. The
      results show that NH and HI subjects have an improved ability to detect
      incremented harmonics when there are spectral decrements surrounding the
      increment. Various decrement widths and depths were compared against subjects'
      equivalent rectangular bandwidths (ERBs). NH subjects effectively used the
      available energy cue in their auditory filters. Some HI subjects, while showing
      significant improvements, underutilized the energy reduction in their auditory
      filters.

PMID- 17004475
TI  - The spatial unmasking of speech: evidence for better-ear listening.
AB  - Speech reception thresholds (SRTs) were measured for target speech presented
      concurrently with interfering speech (spoken by a different speaker). In
      experiment 1, the target and interferer were divided spectrally into high- and
      low-frequency bands and presented over headphones in three conditions: monaural,
      dichotic (target and interferer to different ears), and swapped (the low
      frequency target band and the high-frequency interferer band were presented to
      one ear, while the high-frequency target band and the low-frequency interferer
      band were presented to the other ear). SRTs were highest in the monaural
      condition and lowest in the dichotic condition; SRTs in the swapped condition
      were intermediate. In experiment 2, two new conditions were devised such that one
      target band was presented in isolation to one ear while the other band was
      presented at the other ear with the interferer. The pattern of SRTs observed in
      experiment 2 suggests that performance in the swapped condition reflects the
      intelligibility of the target frequency bands at just one ear; the auditory
      system appears unable to exploit advantageous target-to-interferer ratios at
      different ears when segregating target speech from a competing speech interferer.

PMID- 17004476
TI  - The ability of the parasitoid fly Ormia ochracea to distinguish sounds in the
      vertical plane.
AB  - The parasitic fly Ormia ochracea localizes its host, field crickets, by homing in
      on their calling song. Previous phonotactic studies indicate that their sound
      localization ability in azimuth is extraordinarily acute, but the fly's ability
      to localize the elevation of sound sources has not been tested to date. Here we
      show that in a freely-walking closed-loop Y-maze task elevational performance is
      well above chance, but slightly below the fly's performance in azimuth.
      Immobilizing the head or the halteres (sensory organs of balance) slightly
      lowered elevational discrimination, but performance was still well above chance.
      Because ormiine ears are thought to be symmetric and the pure-tone models of a
      cricket's call used in these experiments contained little to no spectral
      bandwidth, additional studies will be needed to elucidate the underlying cues.
      Nonetheless, it is clear that while walking, Ormia flies are capable of
      distinguishing sound sources that differ only in elevation.

PMID- 17004477
TI  - Underwater auditory localization by a swimming harbor seal (Phoca vitulina).
AB  - The underwater sound localization acuity of a swimming harbor seal (Phoca
      vitulina) was measured in the horizontal plane at 13 different positions. The
      stimulus was either a double sound (two 6-kHz pure tones lasting 0.5 s separated
      by an interval of 0.2 s) or a single continuous sound of 1.2 s. Testing was
      conducted in a 10-m-diam underwater half circle arena with hidden loudspeakers
      installed at the exterior perimeter. The animal was trained to swim along the
      diameter of the half circle and to change its course towards the sound source as
      soon as the signal was given. The seal indicated the sound source by touching its
      assumed position at the board of the half circle. The deviation of the seals
      choice from the actual sound source was measured by means of video analysis. In
      trials with the double sound the seal localized the sound sources with a mean
      deviation of 2.8 degrees and in trials with the single sound with a mean
      deviation of 4.5 degrees. In a second experiment minimum audible angles of the
      stationary animal were found to be 9.8 degrees in front and 9.7 degrees in the
      back of the seal's head.

PMID- 17004478
TI  - The influence of subglottal acoustics on laboratory models of phonation.
AB  - Many previous laboratory investigations of phonation involving physical models,
      excised larynges, and in vivo canine larynges have failed to fully specify the
      subglottal system. Many of these same studies have reported a variety of
      nonlinear phenomena, including bifurcations (e.g., various classes of phonation
      onset and offset, register changes, frequency jumps), subharmonics, and chaos,
      and attributed such phenomena to the biomechanical properties of the larynx.
      However, such nonlinear phenomena may also be indicative of strong coupling
      between the voice source and the subglottal tract. Consequently, in such studies,
      it has not been clear whether the underlying mechanisms of such nonlinear
      phenomena were acoustical, biomechanical, or a coupling of the acoustical and
      biomechanical systems. Using a physical model of vocal fold vibration, and
      tracheal tube lengths which have been commonly reported in the literature, it is
      hypothesized and subsequently shown that such nonlinear phenomena may be
      replicated solely on the basis of laryngeal interactions with the acoustical
      resonances of the subglottal system. Recommendations are given for ruling out
      acoustical resonances as the source of nonlinear phenomena in future laboratory
      studies of phonation.

PMID- 17004479
TI  - Anterior-posterior biphonation in a finite element model of vocal fold vibration.
AB  - In this paper, a finite-element model is used to simulate anterior-posterior
      biphonation [Neubauer et al., J. Acoust. Soc. Am. 110(6), 3179-3192 (2001)]. The
      anterior-posterior stiffness asymmetric factor and the anterior-posterior shape
      asymmetric factor describe the asymmetry properties of vocal folds.
      Spatiotemporal plot, spectral analysis, anterior-posterior fundamental frequency
      ratio, cross covariation function, and correlation length quantitatively estimate
      the spatial asymmetry of vocal fold oscillations. Calculation results show that
      the anterior-posterior stiffness asymmetry decreases the spatial coherence of
      vocal fold vibration. When the stiffness asymmetry reaches a certain level, the
      drop in spatial coherence desynchronizes the vibration modes. The anterior and
      posterior sides of the vocal fold oscillate with two independent fundamental
      frequencies (f(a) and f(p)). The complex spectral characteristics of vocal fold
      vibration under biphonation conditions can be explained by the linear combination
      of f(a) and f(p). Empirical orthogonal eigenfunctions prove the existence of
      higher-order anterior-posterior modes when anterior-posterior biphonation occurs.
      Then, it is found that the anterior-posterior shape asymmetry also decreases the
      spatial coherence of vocal fold vibration, and shape asymmetry is a possible
      reason for anterior-posterior biphonation.

PMID- 17004480
TI  - Theoretical assessment of unsteady aerodynamic effects in phonation.
AB  - This paper ranks the importance of unsteady aerodynamic mechanisms in glottal
      flow. Particular emphasis is given to separation point motion, acceleration of
      glottal airflow by vocal fold motion, and viscous blockage. How nondimensional
      parameters such as the Reynolds, Strouhal, and Womersley numbers help in this
      ranking is also addressed. An equation of motion is derived which includes terms
      explicitly describing the effects of interest, assuming (1) a symmetrical
      glottis, (2) zero pressure recovery downstream of the vocal folds, and (3) a
      quasisteady glottal jet. Estimating the order of magnitude of the terms in this
      equation, it is shown that the flow is characterized by two temporal regimes: (1)
      a flow initiation/shutoff regime where local unsteady acceleration and wall
      motion dominate, and (2) a "quasisteady" regime where the flow is dominated by
      convective acceleration. In the latter case, separation point motion and viscous
      blockage are shown to be out of phase with motion of the vocal folds, thereby
      impacting the shape of the glottal volume flow waveform. The analysis suggests
      that glottal flow may be considered quasisteady only insofar as traditional
      assumptions concerning glottal jet behavior can be confirmed.

PMID- 17004481
TI  - How far, how long: on the temporal scope of prosodic boundary effects.
AB  - Acoustic lengthening at prosodic boundaries is well explored, and the
      articulatory bases for this lengthening are becoming better understood. However,
      the temporal scope of prosodic boundary effects has not been examined in the
      articulatory domain. The few acoustic studies examining the distribution of
      lengthening indicate that boundary effects extend from one to three syllables
      before the boundary, and that effects diminish as distance from the boundary
      increases. This diminishment is consistent with the pi-gesture model of prosodic
      influence [Byrd and Saltzman, J. Phonetics 31, 149-180 (2003)]. The present
      experiment tests the preboundary and postboundary scope of articulatory
      lengthening at an intonational phrase boundary. Movement-tracking data are used
      to evaluate durations of consonant closing and opening movements, acceleration
      durations, and consonant spatial magnitude. Results indicate that prosodic
      boundary effects exist locally near the phrase boundary in both directions,
      diminishing in magnitude more remotely for those subjects who exhibit extended
      effects. Small postboundary effects that are compensatory in direction are also
      observed.

PMID- 17004482
TI  - Voiceless affricate/fricative distinction by frication duration and amplitude
      rise slope.
AB  - Previous psychophysical studies have shown that the perceptual distinction
      between voiceless fricatives and affricates in consonant-vowel syllables depends
      primarily on frication duration, whereas amplitude rise slope was suggested as
      the cue in automatic classification experiments. The effects of both cues on the
      manner of articulation between /integral of/ and /t integral of/ were
      investigated. Subjects performed a forced-choice task (/integral of/ or /t
      integral of) in response to edited waveforms of Japanese fricatives /integral of
      i/, /integral of u/, and /integral of a/. We found that frication duration, onset
      slope, and the interaction between duration and onset slope influenced the
      perceptual distinction. That is, the percent of /integral of/ responses increased
      with an increase in frication duration (experiments 1-3). The percent of
      /integral of/ responses also increased with a decrease in slope steepness
      (experiment 3), and the relative importance between slope portions was not even
      but weighted at onset (experiments 1 and 2). There was an interaction between the
      two cues of frication duration and steepness. The relative importance of the
      slope cue was maximum at a frication duration of 150 ms (experiment 3). It is
      concluded that the frication duration and amplitude rise slope at frication onset
      are acoustic cues that discriminate between /integral of/ and /t integral of/,
      and that the two cues interact with each other.

PMID- 17004483
TI  - Measurements and calculations on the simple up-down adaptive procedure for speech
      in-noise tests.
AB  - The simple up-down adaptive procedure is a common method for measuring speech
      reception thresholds. It is used by the Dutch speech-in-noise telephone screening
      test [National Hearing test; Smits and Houtgast Ear Hear. 26, 89-95 (2005)]. The
      test uses digit triplets to measure the speech reception threshold in noise by
      telephone (SRTT(n)). About 66 000 people took this test within four months of its
      introduction and details were stored of all individual measurements. Analyses of
      this large volume of data have revealed that the standard deviation of SRTT(n)
      estimates increases with hearing loss. This paper presents a calculation model
      which--using an intelligibility function as input--can determine the standard
      deviation of SRTT(n) estimates and the bias for the simple up-down procedure. The
      effects of variations in the slope of the intelligibility function, the guess
      rate, the starting level, the heterogeneity of the speech material, and the
      possibilities of optimizing SRTT(n) measurements were all explored with this
      model. The predicted decrease in the standard deviation of SRTT(n) estimates as a
      result of optimizing the speech material was confirmed by measurements in 244
      listeners. The paper concludes by discussing possibilities for optimizing the
      development of comparable tests.

PMID- 17004484
TI  - Temporal characteristics of nasalization in children and adult speakers of
      American English and Korean during production of three vowel contexts.
AB  - The purpose of this study was to identify and compare the temporal
      characteristics of nasalization in relation to (1) languages, (2) vowel contexts,
      and (3) age groups. Two distinct acoustic energies from the mouth and nose were
      recorded during speech production (/pamap, pimip, pumup/) using two microphones
      to obtain the absolute and proportional measurements on the acoustic temporal
      characteristics of nasalization. Twenty-eight normal adults (14 American English
      and 14 Korean speakers) and 28 normal children (14 American English and 14 Korean
      speakers) participated in this study. In both languages, adults showed shorter
      duration of nasalization than children within all three vowel contexts. The high
      vowel context revealed longer duration of nasalization than the low vowel context
      in both languages. There was no significant difference of temporal
      characteristics of nasalization between American English and Korean. Nasalization
      showed different timing characteristics between children and adults across vowel
      contexts. The results are discussed in association with developmental
      coarticulation and the relationship between acoustic consequences of articulatory
      events and vowel height.

PMID- 17004485
TI  - Speech utterance clustering based on the maximization of within-cluster
      homogeneity of speaker voice characteristics.
AB  - This paper investigates the problem of how to partition unknown speech utterances
      into a set of clusters, such that each cluster consists of utterances from only
      one speaker, and the number of clusters reflects the unknown speaker population
      size. The proposed method begins by specifying a certain number of clusters,
      corresponding to one of the possible speaker population sizes, and then maximizes
      the level of overall within-cluster homogeneity of the speakers' voice
      characteristics. The within-cluster homogeneity is characterized by the
      likelihood probability that a cluster model, trained using all the utterances
      within a cluster, matches each of the within-cluster utterances. To attain the
      maximal sum of likelihood probabilities for all utterances, the proposed method
      applies a genetic algorithm to determine the cluster in which each utterance
      should be located. For greater computational efficiency, also proposed is a
      clustering criterion that approximates the likelihood probability with a
      divergence-based model similarity between a cluster and each of the within
      cluster utterances. The clustering method then examines various legitimate
      numbers of clusters by adapting the Bayesian information criterion to determine
      the most likely speaker population size. The experimental results show the
      superiority of the proposed method over conventional methods based on
      hierarchical clustering.

PMID- 17004486
TI  - Acoustic microscope lens modeling and its application in determining biological
      cell properties from single- and multi-layered cell models.
AB  - The acoustic microscopy technique provides some extraordinary advantages for
      determining mechanical properties of living cells. It is relatively fast, of
      excellent spatial resolution, and of minimal invasiveness. Sound velocity is a
      measure of the cell stiffness. Attenuation of cytoplasm is a measure of
      supramolecular interactions. These parameters are of crucial interest for
      studying cell motility and volume regulations and to establish the functional
      role of the various elements of the cytoskeleton. Using a scanning acoustic
      microscope, longitudinal wave speed, attenuation and thickness profile of a
      biological cell were measured earlier by Kundu et al. [Biophys. J. 78, 2270-2279
      (2000)]. In that study it was assumed that the cell properties did not change
      through the cell thickness but could vary in the lateral direction. In that
      effort the acoustic-microscope-generated signal was modeled as a plane wave
      striking the cell at normal incidence. Such assumptions ignored the effect of
      cell inhomogenity and the surface skimming Rayleigh waves. In this paper a
      rigorous lens model, based on the DPSM (distributed point source method), is
      adopted. For the first time in the literature the cell is modeled here as a multi
      layered material and the effect of some external drug stimuli on a living cell is
      studied.

PMID- 17004487
TI  - Acoustic analysis of vocal development in a New World primate, the common
      marmoset (Callithrix jacchus).
AB  - In contrast to humans and songbirds, there is limited evidence of vocal learning
      in nonhuman primates. While previous studies suggested that primate vocalizations
      exhibit developmental changes, detailed analyses of the extent and time course of
      such changes across a species' vocal repertoire remain limited. In a highly vocal
      primate, the common marmoset (Callithrix jacchus), we studied developmental
      changes in the acoustic structure of species-specific communication sounds
      produced in a social setting. We performed detailed acoustic analyses of the
      spectral and temporal characteristics of marmoset vocalizations during
      development, comparing differences between genders and twin pairs, as well as
      with vocalizations from adult marmosets residing in the same colony. Our analyses
      revealed significant changes in spectral and temporal features as well as
      variability of particular call types over time. Infant and juvenile vocalizations
      changed progressively toward the vocalizations produced by adult marmosets. Call
      types observed early in development that were unique to infants disappeared
      gradually with age, while vocal exchanges with conspecifics emerged. Our
      observations clearly indicate that marmoset vocalizations undergo both
      qualitative and quantitative postnatal changes, establishing the basis for
      further studies to delineate contributions from maturation of the vocal apparatus
      and behavioral experience.

PMID- 17004488
TI  - Estimated communication range of social sounds used by bottlenose dolphins
      (Tursiops truncatus).
AB  - Bottlenose dolphins, Tursiops truncatus, exhibit flexible associations in which
      the compositions of groups change frequently. We investigated the potential
      distances over which female dolphins and their dependent calves could remain in
      acoustic contact. We quantified the propagation of sounds in the frequency range
      of typical dolphin whistles in shallow water areas and channels of Sarasota Bay,
      Florida. Our results indicated that detection range was noise limited as opposed
      to being limited by hearing sensitivity. Sounds were attenuated to a greater
      extent in areas with seagrass than any other habitat. Estimates of active space
      of whistles showed that in seagrass shallow water areas, low-frequency whistles
      (7-13 kHz) with a 165 dB source level could be heard by dolphins at 487 m. In
      shallow areas with a mud bottom, all whistle frequency components of the same
      whistle could be heard by dolphins travel up to 2 km. In channels, high-frequency
      whistles (13-19 kHz) could be detectable potentially over a much longer distance
      (> 20 km). Our findings indicate that the communication range of social sounds
      likely exceeds the mean separation distances between females and their calves.
      Ecological pressures might play an important role in determining the separation
      distances within communication range.

PMID- 17004489
TI  - Vocal development in captive harbor seal pups, Phoca vitulina richardii: age,
      sex, and individual differences.
AB  - The goal of this research was to determine when harbor seal pup vocalizations
      become sufficiently distinctive to allow individual recognition. A total of 4593
      calls were analyzed from 15 captive pups. Nineteen were harsh, broadband,
      staccato calls used in an aggressive context. The rest were tonal "mother
      attraction calls," having an inverted "v"- or "u"-shaped spectrogram with
      harmonics and a fundamental frequency around 200-600 Hz. Calls were individually
      distinctive even in pups less than 2 weeks old, suggesting that mothers may be
      able to recognize pup vocalizations at this early age. Classification rates from
      discriminant function analysis were generally comparable to those of other
      phocids and less than in otariids, supporting the theory that recognition is more
      highly developed in otariids. Significant differences were found between male and
      female pup calls, and there were significant interactions between pup sex and
      age. The results of this study should be interpreted with caution until the
      findings are verified in wild harbor seal pups.

PMID- 17004490
TI  - Preliminary evidence for signature vocalizations among free-ranging narwhals
      (Monodon monoceros).
AB  - Animal signature vocalizations that are distinctive at the individual or group
      level can facilitate recognition between conspecifics and re-establish contact
      with an animal that has become separated from its associates. In this study, the
      vocal behavior of two free-ranging adult male narwhals (Monodon monoceros) in
      Admiralty Inlet, Baffin Island was recorded using digital archival tags. These
      recording instruments were deployed when the animals were caught and held onshore
      to attach satellite tags, a protocol that separated them from their groups. The
      signature content of two vocal categories was considered: (1) combined
      tonal/pulsed signals, which contained synchronous pulsatile and tonal content;
      (2) whistles, or frequency modulated tonal signals with harmonic energy.
      Nonparametric comparisons of the temporal and spectral features of each vocal
      class revealed significant differences between the two individuals. A separate,
      cross-correlation measure conducted on the whistles that accounted for overall
      contour shape and absolute frequency content confirmed greater interindividual
      compared to intraindividual differences. These data are consistent with the
      hypothesis that narwhals produce signature vocalizations that may facilitate
      their reunion with group members once they become separated, but additional data
      are required to demonstrate this claim more rigorously.

PMID- 17004491
TI  - Pitch cue learning in chinchillas: the role of spectral region in the training
      stimulus.
AB  - Chinchillas were trained to discriminate a cosine-phase harmonic tone complex
      (COS) from wideband noise (WBN) and tested in a stimulus generalization paradigm
      with tone complexes in which phase differed between frequency regions. In this
      split-phase condition, responses to complexes made of random-phase low
      frequencies, cosine-phase high frequencies were similar to responses to the COS
      training stimulus. However, responses to complexes made of cosine-phase low
      frequencies, random-phase high frequencies were generally lower than their
      responses to the COS-training stimulus. When tested with sine-phase (SIN) and
      random-phase (RND) tone complexes, responses were large for SIN, but were small
      for RND. Chinchillas were then trained to discriminate infinitely-iterated
      rippled noise (IIRN) from WBN and tested with noises in which the spectral ripple
      differed between frequency regions. In this split-spectrum condition, responses
      were large to noises made of rippled-spectrum low frequencies, flat-spectrum high
      frequencies, whereas responses were generally lower to noises made of flat
      spectrum low frequencies, rippled-spectrum high frequencies. The results suggest
      that chinchillas listen across all frequencies, but attend to high frequencies
      when discriminating COS from WBN and attend to low frequencies when
      discriminating IIRN from WBN.

PMID- 17004492
TI  - A comparison of underwater hearing sensitivity in bottlenose dolphins (Tursiops
      truncatus) determined by electrophysiological and behavioral methods.
AB  - Variable stimulus presentation methods are used in auditory evoked potential
      (AEP) estimates of cetacean hearing sensitivity, each of which might affect
      stimulus reception and hearing threshold estimates. This study quantifies
      differences in underwater hearing thresholds obtained by AEP and behavioral
      means. For AEP estimates, a transducer embedded in a suction cup (jawphone) was
      coupled to the dolphin's lower jaw for stimulus presentation. Underwater AEP
      thresholds were obtained for three dolphins in San Diego Bay and for one dolphin
      in a quiet pool. Thresholds were estimated from the envelope following response
      at carrier frequencies ranging from 10 to 150 kHz. One animal, with an atypical
      audiogram, demonstrated significantly greater hearing loss in the right ear than
      in the left. Across test conditions, the range and average difference between AEP
      and behavioral threshold estimates were consistent with published comparisons
      between underwater behavioral and in-air AEP thresholds. AEP thresholds for one
      animal obtained in-air and in a quiet pool demonstrated a range of differences of
      -10 to 9 dB (mean = 3 dB). Results suggest that for the frequencies tested, the
      presentation of sound stimuli through a jawphone, underwater and in-air, results
      in acceptable differences to AEP threshold estimates.

PMID- 17004493
TI  - A simulation study on tissue harmonic imaging with a single-element intravascular
      ultrasound catheter.
AB  - Recently, in vivo feasibility of tissue harmonic imaging with a mechanically
      rotated intravascular ultrasound (IVUS) catheter was experimentally demonstrated.
      To isolate the second harmonic signal content, a combination of pulse inversion
      and analog filtering was used. In this paper the development of a simulation tool
      to investigate nonlinear IVUS beams is reported, and the influence of transducer
      rotation and axial catheter-to-tissue motion on the efficiency of PI signal
      processing is evaluated. Nonlinear beams were simulated in homogeneous tissue
      mimicking media at a transmit frequency of 20 MHz, which resulted in second
      harmonic pressure fields at 40 MHz. The competing effects of averaging and
      decorrelation between neighboring rf lines on the signal-to-noise ratio (SNR)
      were studied for a single point scatterer. An optimal SNR was achieved when lines
      were combined over 3 degrees - 3.75 degrees. When the transducer was rotated with
      respect to point scatterers, simulating the acoustic response of tissue, the
      fundamental frequency suppression using PI degraded rapidly with increasing
      interpulse angles. The effect of axial catheter-to-tissue motion on the
      efficiency of pulse inversion seemed to be of less influence for realistic motion
      values. The results of this study will aid in the optimization of harmonic IVUS
      imaging systems.

PMID- 17004495
TI  - High-frequency measurements of blast wave propagation.
AB  - Blast wave propagation measurements were conducted to investigate nonlinear
      propagation effects on blast waveform evolution with distance. Measurements were
      made with a wide-bandwidth capacitor microphone for comparison with conventional
      3.175-mm (1/8-in.) microphones with and without baffles. It was found that the
      3.175-mm microphone did not have sufficient high-frequency response to capture
      the actual rise times in some regions. For a source of 0.57 kg (1.25 lb) of C-4
      plastic explosive, the trend observed is that nonlinear effects steepened the
      waveform, thereby decreasing the shock rise time, up to a range of 50 m. At 100
      m, the rise times had increased slightly.

PMID- 17004496
TI  - Mechanisms of irregular vibration in a physical model of the vocal folds.
AB  - Previous investigations have shown that one mechanism of irregular vocal fold
      vibration may be a desynchronization of two or more vibratory modes of the vocal
      fold tissues. In the current investigation, mechanisms of irregular vibration
      were further examined using a self-oscillating, physical model of vocal fold
      vibration, a hemi-model methodology, and high-speed, stereoscopic, digital
      imaging. Using the method of empirical eigen-functions, a spatiotemporal analysis
      revealed mechanisms of irregular vibration in subharmonic phonation and
      biphonation, which were not disclosed in a standard acoustic spectrum.

PMID- 17004497
TI  - Imaging marine geophysical environments with vector acoustics.
AB  - Using vector acoustic sensors for marine geoacoustic surveys instead of the usual
      scalar hydrophones enables one to acquire three-dimensional (3D) survey data with
      instrumentation and logistics similar to current 2D surveys. Vector acoustic
      sensors measure the sound wave direction directly without the cumbersome arrays
      that hydrophones require. This concept was tested by a scaled experiment in an
      acoustic water tank that had a well-controlled environment with a few targets.
      Using vector acoustic data from a single line of sources, the three-dimensional
      tank environment was imaged by directly locating the source and all reflectors.

PMID- 17004498
TI  - [Epidemiologic research in industrial medicine].
AB  - The article describes methodologic approach and principles of epidemiologic
      research management in occupational medicine. The authors defined relative risk
      and conditionality of occupational disease by causative factor of occupational
      environment.

PMID- 17004499
TI  - [Occupationally related morbidity: basic methodology].
AB  - The authors considered basic methodology concerning evaluation of occupationally
      related morbidity: terminology, legal and methodologic items. Suggestions
      included new single-numerical index for occupationally related morbidity,
      considering categories of risk, severity and occupational connection.

PMID- 17004500
TI  - [Ethics and informing an employee on occupational risk].
AB  - Considering biologic ethics and information right, the authors justify necessary
      formation a system providing materials on occupational risks for employees in
      contemporary industry. Problems associated with collecting information materials
      cover linguistic aspect and difficulty in receiving reliable data on diseases
      prognosis meeting criteria of evidence-based medicine.

PMID- 17004501
TI  - [Immunologic aspects of ecologically related and occupational diseases in East
      Siberia].
AB  - The authors report on immune reactivity state in adults and children dwellers of
      industrial cities varying in level and traits of environmental pollution. The
      article demonstrates role and importance of immunologic, immunogenetic mechanisms
      in development of ecologically related and occupational diseases.

PMID- 17004502
TI  - [Immune state of arterial hypertension and hypercholesterolemia patients engaged
      into construction materials production].
AB  - The authors studied immune state in individuals engaged in construction materials
      production, in accordance with presence or absence of arterial hypertension and
      hypercholesterolemia. Findings are depressed nonspecific resistance parameters
      and T-cell reactions in immune state.

PMID- 17004503
TI  - [Activity of enzymes in peripheral lymphocytes in simulated allergic disease
      caused by combined effects of chemical and biologic occupational factors].
AB  - Peripheral lymphocytes reaction--lower succinate dehydrogenase activity,
      nonspecific esterase activity and stimulated lactate dehydrogenase--after
      combined biologic and chemical influence suggests progressive allergic process,
      depends on severity of antigen load and is not detected for separate factors
      influence.

PMID- 17004504
TI  - [Physiologic and hygienic principles underlying creation of clothes protecting
      against cold].
AB  - The article presents principles underlying creation of clothes protecting against
      cold, in accordance with specific usage conditions (ambient air temperature and
      speed, ergonomic traits and metabolic level of work, duration of cold exposure).
      The authors listed requirements to thermal protection of clothes and to separate
      entities (hat, gloves, shoes) in relation to various climate regions. Major steps
      of creation and evaluation of the clothes are demonstrated.

PMID- 17004505
TI  - [On evaluating functional state of human operator].
AB  - Analysis of patents for inventions evaluating functional state proved decreased
      research and invention activities in Russian Federation since 1990 till 2004 and
      lower innovation prospects of inventions.

PMID- 17004506
TI  - [Personnel and bed supplies for Occupational Diseases Centers in Russian
      Federation].
AB  - The author presents calculations of required quantities of beds and staffers for
      Occupational Diseases Centers. Those calculations are based on scientific norms
      concerning activities of doctors in the Centers and number of staffers exposed to
      work conditions that do not meet sanitary and hygienic regulations on Russian
      Federation territory. Evidence is that most territories face actual staffers and
      beds numbers much lower than quantities necessary for effective occupational
      medical care.

PMID- 17004507
TI  - [Occupational morbidity in Ulianovsk region].
AB  - Retrospective analysis of occupational morbidity in Ulianovsk region proved a
      definite trend to increase in occupational diseases number. The authors
      necessitated creation of programs on occupational diseases prevention in the
      region.

PMID- 17004508
TI  - Palliation of malignant dysphagia in esophageal cancer: a literature-based
      review.
AB  - Esophageal cancer is a lethal malignancy and adenocarcinoma of the esophagus is
      increasing in incidence. Most patients present with locally advanced,
      unresectable or metastatic disease. The 5-year survival rate of patients with
      esophageal cancer is < 20%. Dysphagia is the most common presenting symptom of
      this disease and leads to nutritional compromise, pain, and deterioration of
      quality of life. Palliation is an important goal of esophageal cancer therapy.
      Severity is commonly measured using a dysphagia grade, and dysphagia is an
      integral component of quality-of-life instruments, such as FACT-E and EORTC-OES
      24. Investigation of dysphagia includes radiographic studies such as barium or
      Gastrografin swallow, esophagogastroduodenoscopy, endoscopic ultrasonography, and
      other staging studies for esophageal cancer. Current management options for the
      palliation of dysphagia include esophageal dilatation, intraluminal stents,
      Nd:YAG laser therapy, photodynamic therapy, argon laser, systemic chemotherapy,
      external beam radiation therapy, brachytherapy, and combined chemoradiation
      therapy. The clinical situation, local expertise, and cost effectiveness play an
      important role in choosing the appropriate treatment modality. The benefits and
      disadvantages of these approaches along with a concise review of the literature
      are presented.

PMID- 17004509
TI  - Choosing the correct modality for the treatment of dysphagia in the patient with
      esophageal cancer.

PMID- 17004510
TI  - Dysphagia: we can relieve this symptom.

PMID- 17004511
TI  - Prevention and management of arm lymphedema in the patient with breast cancer.
AB  - Arm lymphedema develops in 10%-35% of patients who undergo axillary dissection
      and/or nodal radiation therapy for breast cancer. Lymphedema that occurs in the
      first 18 months after surgery or radiation is described as acute lymphedema, and
      can be managed with conservative measures such as elevation of the arm and mild
      compression. Chronic lymphedema, the more serious form, has a progressive and
      generally irreversible course. Risk factors associated with the development of
      lymphedema include greater extent of axillary surgery; more positive axillary
      nodes; a postoperative axillary hematoma, seroma, or infection; and use of nodal
      radiation. The most common method of lymphedema measurement is the circumference
      10 cm above and below the olecranon process, although most clinicians do not take
      measurements in the preoperative setting for comparison.Treatment strategies
      include elevation, complete decongestive physiotherapy, pneumatic pumps, and,
      after failure of all other methods, surgery. Lymphangiosarcoma is a rare and late
      complication of longstanding extremity lymphedema. The advent of sentinel lymph
      node biopsy as an alternative to axillary dissection should decrease the rate of
      lymphedema. The increasing number of breast cancer survivors and the high
      prevalence of the disease will continue to make lymphedema a significant
      consequence of breast cancer treatment.

PMID- 17004512
TI  - Breast cancer treatment-related lymphedema--A continuing problem.

PMID- 17004513
TI  - Current issues in the management of lymphedema in breast cancer patients.

PMID- 17004514
TI  - Chemotherapy-induced peripheral neuropathy: A need for standardization in
      measurement.

PMID- 17004515
TI  - Combination therapy for chemotherapy-induced nausea and vomiting in patients
      receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and
      aprepitant.
AB  - The objective of this multicenter, phase II, open-label study was to evaluate the
      safety and efficacy of the newest 5-hydroxytryptamine3 (5-HT3) receptor
      antagonist, palonosetron, plus dexamethasone and aprepitant in preventing nausea
      and vomiting in patients receiving moderately emetogenic chemotherapy. Eligible
      patients received a single intravenous dose of palonosetron (0.25 mg on day 1 of
      chemotherapy), along with 3 daily oral doses of aprepitant (125 mg on day 1,80 mg
      on days 2 and 3) and dexamethasone (12 mg on day 1,8 mg on days 2 and 3).
      Efficacy and safety data were obtained from patient diaries and adverse event
      reporting. Fifty-eight patients were evaluable; 47% were women with breast cancer
      and 52% received cyclophosphamide-based chemotherapy. The proportion of patients
      with complete response (no emesis and no rescue medication) was 88% during the
      acute (0-24 hours) interval, 78% during the delayed (> 24-120 hours) interval,
      and 78% during the overall (0-120 hours post chemotherapy) interval. More than
      90% of patients during all time intervals had no emetic episodes, and between 57%
      and 71% of patients reported no nausea during each of the 5 days post
      chemotherapy. Treatment was well tolerated, with no unexpected adverse events.
      These data demonstrate that palonosetron in combination with dexamethasone and
      aprepitant is safe and highly effective in preventing chemotherapy-induced nausea
      and vomiting in the days following administration of moderately emetogenic
      chemotherapy.

PMID- 17004516
TI  - Selecting antiepileptic drugs for symptomatic patients with brain tumors.

PMID- 17004517
TI  - Medical school graduates of 2006: "hooded, but not hoodwinked".

PMID- 17004518
TI  - The Katrina public health debacle: lessons learned and lessons ignored.

PMID- 17004519
TI  - Residency work hour limits: a little time off, a lot to consider.

PMID- 17004520
TI  - Retinitis pigmentosa and common variable immunodeficiency disease: associated or
      separate?

PMID- 17004521
TI  - Adverse drug reactions.

PMID- 17004522
TI  - Dipyrone (metamizole) use in the United States: a lethal tango?

PMID- 17004523
TI  - The emerging role of group A beta hemolytic Streptococcus as retropharyngeal
      abscess pathogen in children--a change which doesn't matter?

PMID- 17004524
TI  - How do internal medicine residency programs evaluate their resident float
      experiences?
AB  - OBJECTIVES: We surveyed the nation's internal medicine residency training program
      directors to determine the range and frequency of existing methods by which float
      experiences are evaluated. METHODS: We sent questionnaires to the program
      directors of all 396 internal medicine residency training program sites in the
      country. Information requested included program characteristics, months devoted
      to float experiences in each year of training, and the location and purpose of
      the rotation. Program directors were also asked to choose among descriptors
      characterizing the evaluative process. RESULTS: There were 139 responding
      programs (39%), 134 with data that could be aggregated. Responding programs were
      similar to all programs nationally in the distributions of size and university
      sponsorship. Overall, 76% of programs employed a night float for any period of
      time, and 71% currently had one, on average for 6.7 years. Mean months of float
      experience during residency was 2.4 months, significantly longer in programs that
      were not university based. Float experiences were evaluated in 89% of those
      programs who employed them, with ten different methods reported. University-based
      programs were significantly less likely to use chart review as a method of
      evaluation, but no other differences in methodology were significant.
      CONCLUSIONS: Float rotations are common among internal medicine residency
      training programs. Evaluative methods vary, but one or more are applied in the
      vast majority of programs.

PMID- 17004525
TI  - Metamizole use among Hispanics in Miami: report of a survey conducted in a
      primary care setting.
AB  - BACKGROUND: Metamizole (dipyrone) is a myelotoxic, nonsteroidal anti-inflammatory
      agent that has been banned from the US market since 1979. However, dipyrone may
      be purchased in some areas of the US. We conducted a survey in a primary care
      setting in Miami, Florida to determine the prevalence of metamizole possession
      and use among Hispanics living in this area. METHODS: Participants consisted of
      137 Hispanic outpatients interviewed consecutively during a primary care visit in
      the month of February 2005. RESULTS: Metamizole was possessed by 28% of the
      surveyed population. The most common reasons for using dipyrone were pain (72%)
      and fever (24%). The vast majority of patients had purchased the medication in
      Latin America (95%), in most instances without a prescription (95%). Nineteen
      patients (13%) had used the medication during the previous year. CONCLUSIONS:
      Metamizole is available to Latino immigrants who reside in the US, despite the
      FDA ban imposed in 1977.

PMID- 17004526
TI  - Retropharyngeal abscess in children: the emerging role of group A beta hemolytic
      streptococcus.
AB  - BACKGROUND: Because of a recent increase in the number of cases of
      retropharyngeal abscess (RPA) admitted to our hospital, we reviewed the
      incidence, microbiology, and treatment outcome of RPA during an 11-year period
      (1993-2003). METHODS: A retrospective review of medical records of children with
      RPA. RESULTS: Sixty-seven children (46 males) with RPA were identified,
      representing a 4.5-fold increase in incidence over a previous 12-year period. The
      majority (66%) of patients presented during the last 4 years. Computed tomography
      revealed inflammatory or ring enhancing lesion in all patients. Abscess drainage
      was performed in 51 (76%) patients. A total of 101 isolates (84 aerobes, 17
      anaerobes) were recovered from 41 specimens (a mean of 2.5 isolates per
      specimen). Group A beta hemolytic streptococcus (GABHS) was recovered from 22
      (54%) of 41 specimens compared with 6 (35%) of 17 over the previous 12 years.
      Treatment included i.v. antibiotics: ampicillin/sulbactam or clindamycin plus
      either cefuroxime or ceftriaxone, followed by oral amoxicillin/clavulanate or
      clindamycin. All patients recovered. CONCLUSIONS: RPA, an aerobic/anaerobic
      polymicrobial infection, is increasing in frequency and is associated with
      increased recovery of GABHS in our patients. Whether this rise in incidence is
      due to increased invasiveness of GABHS strains is to be determined.

PMID- 17004527
TI  - Hurricane Katrina: medical response at the Houston Astrodome/Reliant Center
      Complex.
AB  - On September 1, 2005, with only 12 hours notice, various collaborators
      established a medical facility--the Katrina Clinic--at the Astrodome/Reliant
      Center Complex in Houston. By the time the facility closed roughly two weeks
      later, the Katrina Clinic medical staff had seen over 11,000 of the estimated
      27,000 Hurricane Katrina evacuees who sought shelter in the Complex. Herein, we
      describe the scope of this medical response, citing our major challenges,
      successes, and recommendations for conducting similar efforts in the future.

PMID- 17004528
TI  - Adult health screening and referral in the emergency department.
AB  - INTRODUCTION: The United States Public Health Service (USPHS) recommends using
      all available patient encounters to provide preventive healthcare to patients.
      Many studies have demonstrated the importance of performing preventive care in
      the emergency department (ED). These studies have used the ED as a location for
      patient identification and treatment, rather than as a referral site. The primary
      objective of this study was to identify and refer patients with unmet healthcare
      needs seen in the Emergency Department. A secondary objective was to determine if
      the patient would accept health referrals and follow-up with a doctor or clinic.
      METHODS: Age and gender-specific algorithms were developed from the USPHS
      Clinicians' Book of Preventative Health, Second Edition. A convenience sample of
      patients who presented to the emergency department was asked to participate in
      the study to obtain 50 subjects in each age and gender grouping. After one week
      the patients were followed up by telephone, and after one month the computer
      database was queried to confirm that an appointment had been made with a doctor
      or clinic as recommended. RESULTS: Three hundred and twelve patients in the
      Emergency Department were enrolled in the study. The demographic profile of the
      patients surveyed consisted of 152 (48.7%) African Americans, 81 (26.0%)
      Hispanics, and 12 (3.8%) Caucasians. Of those enrolled, 59.9% had a primary care
      physician, and 78.2% had insurance coverage. The study revealed that 28.8% of the
      subjects did not need a referral, 51.3% needed 1 to 3 referrals, and 19.9% needed
      4 to 8 referrals. The most common needs were for tetanus immunizations (41.2%)
      and stool for occult blood (41.0%); the least common was for Pap smears (2.6%)
      and blood pressure (2.0%). Most patients accepted the referrals (88.3%), but only
      a fourth of those (22.6%) reported making a follow-up appointment. The
      appointment was confirmed in the computer system in 39.6% of the cases. The
      highest rate of follow-up was for prostate screening (41.4%); the least was for
      drug abuse (0.0%). CONCLUSION: Most of the patients in this study were found to
      have unmet healthcare needs. Many of the patients were given referrals and
      followed up with the clinic or physician for the healthcare problems identified.
      This study reinforces the value of the USPHS guideline to use all available
      patient encounters for preventive healthcare.

PMID- 17004529
TI  - Surveillance of the colorectal cancer disparities among demographic subgroups: a
      spatial analysis.
AB  - OBJECTIVE: The literature suggests that colorectal cancer mortality in Texas is
      distributed inhomogeneously among specific demographic subgroups and in certain
      geographic regions over an extended period. To understand the extent of the
      demographic and geographic disparities, the present study examined colorectal
      cancer mortality in 15 demographic groups in Texas counties between 1990 and
      2001. METHODS: The Spatial Scan Statistic was used to assess the standardized
      mortality ratio, duration and age-adjusted rates of excess mortality, and their
      respective p-values for testing the null hypothesis of homogeneity of geographic
      and temporal distribution. RESULTS: The study confirmed the excess mortality in
      some Texas counties found in the literature, identified 13 additional excess
      mortality regions, and found 4 health regions with persistent excess mortality
      involving several population subgroups. CONCLUSION: Health disparities of
      colorectal cancer mortality continue to exist in Texas demographic
      subpopulations. Health education and intervention programs should be directed to
      the at-risk subpopulations in the identified regions.

PMID- 17004530
TI  - Black/white differential use of health services by young children in a rural
      Mississippi community.
AB  - BACKGROUND AND OBJECTIVES: Use of health services in rural communities has not
      been well studied. We explored how black and white children used health services
      in a rural Mississippi community. METHODS: Data were prospectively collected for
      396 children attending a private practice to determine if race was associated
      with the use of health services in this community. RESULTS: White children made
      more sick contacts than black children (P < 0.001). Black children (36%) were
      more likely to be treated in the emergency room than white children (24%; P =
      0.013). There was no black-white difference in the hospitalization rates,
      although white children were more likely to undergo ear-nose-throat (ENT) surgery
      for pressure equalizing tube (PET) placement, and/or tonsillectomy and
      adenoidectomy (T and A; P < 0.001). Even after controlling for various
      confounders, the frequency of all physician sick contacts was twice as high for
      white children than for black children (RR = 2.17; 95% C.I. = 1.32-3.58).
      CONCLUSION: Overall, black children used disproportionately fewer health services
      than their white counterparts, but used significantly higher emergency room
      services. Private insurance coverage was the single most significant variable
      that accounted for the black-white differential use of the emergency room.

PMID- 17004531
TI  - Unicameral (simple) bone cysts.
AB  - Since their original description by Virchow, simple bone cysts have been studied
      repeatedly. Although these defects are not true neoplasms, simple bone cysts may
      create major structural defects of the humerus, femur, and os calcis. They are
      commonly discovered incidentally when x-rays are taken for other reasons or on
      presentation due to a pathologic fracture. Various treatment strategies have been
      employed, but the only reliable predictor of success of any treatment strategy is
      the age of the patient; those being older than 10 years of age heal their cysts
      at a higher rate than those under age 10. The goal of management is the formation
      of a bone that can withstand the stresses of use by the patient without evidence
      of continued bone destruction as determined by serial radiographic follow-up. The
      goal is not a normal-appearing x-ray, but a functionally stable bone.

PMID- 17004532
TI  - Wegener granulomatosis: a case report and update.
AB  - Wegener granulomatosis (WG) is a systemic disease of unknown etiology
      characterized by necrotizing granulomatous inflammation, tissue necrosis, and
      variable degrees of vasculitis in small and medium-sized blood vessels. The
      classic clinical pattern is a triad involving the upper airways, lungs and
      kidneys. Ninety percent of patients present with symptoms involving the upper
      and/or lower airways, and 80% will eventually develop renal disease. WG should be
      suspected in any patient with progressive or unresponsive sinus disease,
      glomerulonephritis, pulmonary hemorrhage, mononeuritis multiplex or unexplained
      multisystem disease. Before the routine use of glucocorticoids and
      cyclophosphamide, the one year mortality was 82%. However in 1973, Fauci and Wolf
      discovered that daily prednisone and cyclophosphamide induced complete remission
      in 75% of patients. The continued use of prednisone and cyclophosphamide for 1
      year past remission leads to marked improvement in more than 90% of patients;
      however, is also associated with serious toxicities. Depending on the disease
      severity, current treatments employ induction with short-term cyclophosphamide
      followed by less toxic agents such as methotrexate to maintain disease remission.
      Although it is a rare disorder, it is pertinent to internists because it is a
      multisystem disease that presents in a variety of ways. We describe a 63-year-old
      white male with WG who presented with progressively worsening headaches,
      bilateral eye redness, epistaxis, hemoptysis and an unintentional 20 pound weight
      loss, and review the current treatment recommendations.

PMID- 17004533
TI  - Retinitis pigmentosa and hypogammaglobulinemia.
AB  - This report describes a family demonstrating an unusual association of retinitis
      pigmentosa and hypogammaglobulinemia. The proband in this family suffered from
      another rare illness, ie, Sertoli cell only syndrome. The incidence of retinitis
      pigmentosa is 1 in 5,000 and that of common variable immunodeficiency state is 1
      in 100,000, making a chance association of these illnesses very unlikely.

PMID- 17004534
TI  - An adolescent with abdominal pain taking isotretinoin for severe acne.
AB  - A 19-year-old female patient is presented who was taking isotretinoin for severe,
      nodulocystic acne. She subsequently developed abdominal pain during the course of
      treatment, thought to be related to an adverse reaction to the medication. A
      concerning side effect of isotretinoin is hypertriglyceridemia, which may be a
      cause of pancreatitis. A lipase level was determined to be elevated in this case.
      The patient was diagnosed with acute pancreatitis and the offending agent was
      discontinued. Clinicians need to be aware of the side effects when prescribing
      isotretinoin for recalcitrant acne.

PMID- 17004535
TI  - Sarcoidosis presenting as intrascrotal mass: case report and review.
AB  - Sarcoidosis is a multisystemic disease that usually involves the lungs and lymph
      nodes, but almost any organ can be involved. Genitourinary involvement with
      sarcoidosis is extremely rare. We report the case of a 30-year-old African
      American male who presented with a right-sided intrascrotal mass and diffuse
      lymphadenopathy. On further workup, he was found to have sarcoidosis. Two months
      of corticosteroid treatment resulted in the disappearance of his intrascrotal
      mass.

PMID- 17004536
TI  - Multiple venous thromboses in a young man with sarcoidosis: is there a relation
      between sarcoidosis and venous thrombosis?
AB  - We describe the case of a 33-year-old African-American male who presented with
      multiple deep venous thromboses of the upper and lower extremities.
      Hypercoagulable workup was unrevealing. A chest x-ray showed bilateral hilar
      lymph node enlargement. Mediastinoscopy with hilar lymph node biopsy was
      performed. Lymph node histopathologic examination showed noncaseating granulomas.
      Lymph node tissue culture and special stains were negative for mycobacterial or
      fungal infection. This is an unusual case of multiple deep venous thromboses and
      sarcoidosis. The subject of sarcoidosis and venous thrombosis is discussed.

PMID- 17004537
TI  - Cardiac perforation and tamponade: a potentially fatal complication during
      transjugular intrahepatic portosystemic shunt placement.
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) is a low-resistance channel
      between the hepatic vein and the intrahepatic portion of the portal vein. This is
      an important addition to the therapeutic armamentarium against portal
      hypertension. Complications are either technical or due to the creation of a
      shunt. Procedure-related mortality is about 0 to 2%. Cardiac perforation, one of
      the rarest complications during TIPS, can occur while traversing the catheter
      from the jugular vein past the right atrium to enter the hepatic vein. We are
      reporting the case of a 50-year-old woman who became acutely hypotensive with
      cardiovascular compromise during the TIPS procedure. A stat echocardiogram
      confirmed cardiac tamponade and emergency pericardiocentesis resulted in
      improvement of hemodynamic status with complete recovery.

PMID- 17004538
TI  - Pulmonary infarction due to vascular stent migration.
AB  - The case of a patient who developed pulmonary infarction after a vascular stent
      migrated to her pulmonary artery is presented. Stent migration is a known
      complication of vascular stents. The incidence is reported to be as low as 3%.
      Cases have been reported of successful retrieval of the stents. There are also
      reports of the stents being left in place without attempts to retrieve them, due
      to lack of symptoms. In this case, we opted to monitor the patient, despite the
      presence of pulmonary infarction. She appears to be tolerating the stent without
      any further complications.

PMID- 17004539
TI  - An over-the-counter omission.
AB  - Despite the widespread use of over-the-counter (OTC) medications, their
      utilization is rarely ascertained at hospital admission. Presented here is an
      interesting case of acute renal failure and hemolytic anemia attributable to a
      commonly utilized OTC medication. The chronic use of phenazopyridine accounted
      for all of these findings. Upon discontinuation, everything normalized within one
      month. Although the differential diagnosis for renal failure and hemolytic anemia
      is extensive, scleral icterus, normal bilirubin, and orange-colored urine raised
      the suspicion of phenazopyridine use. This case report highlights overuse of
      common OTC medications, as well as a lack of knowledge of potential adverse
      reactions. With history-taking vigilance and patient education, adverse events
      from OTC medications can be minimized.

PMID- 17004540
TI  - A clinical report of adverse health effects due to bed sharing in two children
      with spinal cord injury and traumatic brain injury.
AB  - This paper explores the possibility that bed sharing may carry particular risks
      for children with special healthcare needs (CSHCN). Two cases of CSHCN who may
      have sustained adverse health effects from bed sharing are described. These two
      case reports indicate that CSHCN may be particularly susceptible to risks
      associated with bed sharing. Healthcare providers for CSHCN may need to inquire
      about patients' sleeping arrangements and, when bed sharing is acknowledged,
      provide counseling regarding the potential risks and benefits. They may need to
      monitor more closely for adverse events when bed sharing is a factor and should
      consider reporting health problems that may have occurred in concurrence with bed
      sharing.

PMID- 17004541
TI  - Small bowel obstruction caused by phytobezoar and associated with vitamin B12
      deficiency.

PMID- 17004542
TI  - Burst of autoimmunity with the emergence of primary Sjogren syndrome, cholestatic
      autoimmune hepatitis and latent autoimmune diabetes of adults (LADA).

PMID- 17004543
TI  - Effect of statins on low-density lipoprotein size: a new role in cardiovascular
      prevention?

PMID- 17004544
TI  - Public outreach depression screening: collaboration between medical education and
      integrative primary care.

PMID- 17004545
TI  - Patient's page. New screening techniques for colon cancer. Is bed sharing safe?

PMID- 17004546
TI  - Looking back: one hundred years in rheumatology.

PMID- 17004547
TI  - Postoperative bleeding: coagulopathy, bleeding, hemothorax.
AB  - Several issues are involved in determining a patient's risk for postoperative
      hemorrhage and in managing this potential postoperative complication. The impact
      of minimally invasive procedures on the incidence of this complication is
      addressed in this article.

PMID- 17004548
TI  - Chylothorax.
AB  - Chylothorax is a rare complication of pulmonary resection. It requires prompt
      treatment, which is initially conservative. This treatment consists of drainage,
      nutritional support, and measures to diminish chyle flow. Surgical intervention
      is indicated when conservative management is ineffective. Delay in surgical
      intervention leads not only to serious metabolic, nutritional, and immunologic
      disturbances from the loss of chyle but also increases the risk for adhesion
      formation, loculation, organization, and infection of the chylothorax, making
      subsequent surgical attempts difficult and increasing postoperative morbidity and
      mortality. VATS provides a minimally invasive approach for the treatment of
      chylothorax complicating pulmonary resection. Clipping of the thoracic duct or
      chemical pleurodesis may be performed with minimal morbidity and mortality.
      Conservative treatment is expensive and fails in most patients who have high
      output chylous fistulae. On the other hand, VATS is uniformly effective, is less
      expensive, and has low morbidity. Indeed, VATS is rapidly becoming the preferred
      approach for the management of chylothorax complicating pulmonary resection. The
      need to prevent the occurrence of a chylothorax by careful dissection techniques
      and liberal clipping of lymphatic vessels particularly in areas of high anatomic
      risk during the initial operation cannot be overemphasized.

PMID- 17004549
TI  - Postpneumonectomy and postlobectomy empyema.
AB  - Although similar strategies are used in the management of PPE and PLE, these
      conditions need to be viewed as two separate entities. For the purpose of
      devising the appropriate management strategy, PPE should be divided into early
      and late, with and without mediastinal induration and extensive pleural space
      contamination. If at all possible, PLE should be managed as a postpneumonic
      empyema with prolonged chest tube drainage. The key to these conditions is
      prevention.

PMID- 17004550
TI  - Complications of pulmonary resection: postpneumonectomy pulmonary edema and
      postpneumonectomy syndrome.
AB  - Bassed on the authors' review of the unusual variants of PPS and the body of
      published experience, a revision of the current classification scheme for PPS
      into a more comprehensive form is justified as follows: (1) by the nature of
      obstruction; and (2) by the time of onset. This classification encompasses early
      and late symptom onset, as well as considering both airway and vascular
      compression. This scheme argues in favor of an expanded cardiac work-up in
      addition to the measures outlined previously for airway assessment. Althought PPS
      remains a rare clinical entity, the refinement in the understanding of this
      condition and the evolution of treatment options have vastly improved patient
      outcomes. A careful evaluation of the patient must be done before embarking on
      treatment owing to the numerous etiologies for progressive dyspnea in the
      pneumonectomy patient.

PMID- 17004551
TI  - Postoperative respiratory failure.
AB  - This analysis differentiates the causes of postoperative respiratory failure.
      Respiratory failure in thoracic patients is broken down into two distinct groups,
      aspiration and pneumonia, promoting actions to prevent respiratory failure. The
      goal is to develop different strategies to avoid postoperative respiratory
      failure using an active approach (what can be done in the management of patients
      undergoing lung resection to prevent problems) rather than passive approach (what
      patient factors caused problems after surgery). Before that analysis, the
      operative risks after lung resections (lobectomies, pneumonectomies, elderly
      patients) and esophagectomies are reviewed to understand the data.

PMID- 17004552
TI  - Airway complications after pulmonary resection.
AB  - Airway complications following pulmonary resection remain a challenging problem.
      A high degree of clinical suspicion, contrasted CT imaging, and early reoperation
      are crucial in preserving viable lung parenchyma following the anatomic
      compromise of lobar torsion. Likewise, early recognition and expeditious drainage
      of the pleural space in the setting of bronchial dehiscence may help prevent the
      aspiration pneumonia and consequent respiratory failure that is the leading cause
      of death in this patient population; A variety of interventions to manage stump
      dehiscence are possible, but successful management still remains difficult and
      requires an individualized approach. Attention to technical details and avoidance
      of extensive dissection and tension should yield acceptably low rates of
      postoperative stenosis following bronchoplastic resection. These common themes of
      precise surgical technique, vigilance in the perioperative period, and classic
      sound judgment in addressing problems effectively and expeditiously remain
      pivotal in the minimization of sequelae from morbid airway complications.

PMID- 17004554
TI  - Air leak and pleural space management.
AB  - Parenchymal air leakage following lung resection is, unfortunately, the rule and
      not the exception. Although air leakage does negatively impact the patient's
      hospital course, it is self-limiting in most cases. If there is no sign of
      improvement in the air leak by 1 week, bronchoscopy is recommended. There is no
      definitive timing of reintervention, but if the lung is expanded, expectant
      management is still the most prudent course of action. For larger air leaks,
      especially in the presence of an incompletely expanded lung or residual
      ipsilateral pleural space, reintervention should be considered if there is no
      improvement by 1 to 2 weeks.

PMID- 17004553
TI  - Cardiovascular complications after lung surgery.
AB  - Cardiovascular complications following thoracic surgery remain a challenge to the
      physician, the hospital, and the health care system. These events add
      significantly to morbidity, mortality, and the cost of care of the general
      thoracic surgery patient. A proactive approach to identify patients at high risk
      for such complications is needed. In this manner, one may enhance prevention and
      treatment if problems occur. A thoughtful and complete preoperative risk
      assessment can identify patients who have potential contributing comorbidities,
      leading to a reduced incidence of postoperative events. Standardization of
      preoperative, intraoperative, and postoperative care can reduce postoperative
      events. Implementation of guidelines and pathways that are evidence based can
      lead to enhanced patient care, better patient and staff satisfaction, and
      improved outcomes from the operation. Although postoperative cardiac events
      cannot be completely eliminated from the thoracic surgery population, the
      prevention, treatment, and follow-up strategies outlined herein can attenuate
      these significant morbid and mortal events.

PMID- 17004555
TI  - Nerve injury: injury to the recurrent laryngeal, phrenic, vagus, long thoracic,
      and sympathetic nerves during thoracic surgery.
AB  - Nerve injury occurs in about 1% of patients undergoing thoracic surgery. Most
      commonly, it is the result of surgical trauma specific to the area of operation.
      Alternatively, it may be due to retraction on adjacent structures during the
      exposure of complex surgical procedures. This article reviews the most common
      types of nerve injury and discusses the pathophysiology, etiology, diagnosis, and
      treatment of each.

PMID- 17004556
TI  - Chest wall/diaphragmatic complications.
AB  - This article discusses the prevention and management of chest wall and
      diaphragmatic complications after extrapleural pneumonectomy, the prevention of
      thoracoplasty scoliosis, the complications after chest wall resection, and the
      presentation, prevention, and management of chest wall hernia. Appropriate
      preoperative assessment and patient selection, meticulous attention to detail
      intraoperatively, and diligent postoperative observation and care are needed to
      prevent these events.

PMID- 17004557
TI  - Management of postthoracotomy pain: acute and chronic.
AB  - Given the discomfort of thoracic surgical incisions, thoracic surgeons must
      understand and use contemporary multimodality pain treatments. Acute
      postthoracotomy pain not only causes psychologic distress to the patient but also
      has detrimental effects on pulmonary function and postoperative mobility, leading
      to increased morbidity. By choosing the most appropriate and least traumatic
      surgical incision, adhering to meticulous surgical techniques, and avoiding
      intercostal nerve injury or rib fractures, surgeons can minimize postoperative
      pain. Aggressive perioperative and postoperative pain management is best
      accomplished with use of an epidural anesthetic and covering breakthrough pain
      with an IV-PCA. Alternatively, an infusion system for continuous administration
      of local anesthetics directly in the subpleural plane, posterior to the
      intercostal incision, also provides excellent pain control. Again, use of an IV
      PCA as adjuvant therapy is recommended. With careful planning, severe pain and
      its negative impact on thoracic surgical patients can be prevented.

PMID- 17004558
TI  - Gastrointestinal-related complications after major lung surgery.
AB  - Numerous factors increase the risk for GI complications in patients undergoing
      lung resection. It seems that the more debilitated the patient and the more
      extensive the COPD, the higher the risk. The most commonly reported cause of
      mortality after lung surgery is multi-organ failure accompanying respiratory
      failure. The trigger site for multi-system failure is often the GI system. Some
      risk factors cannot be altered, such as diabetes and the cardiovascular effects
      of long-term smoking. Other factors, such as steroid dose, anemia, hypoxia,
      narcotics, and other medications, can be modified. In addition, a high suspicion
      and early recognition of GI problems in the postoperative period can decrease
      their mortality. Severe GI complications after lung resection may be frustrating
      and poorly tolerated in high-risk patients, with little margin for error.
      Heightened awareness along with early recognition can prevent these complications
      and alter their outcome.

PMID- 17004559
TI  - Professional development: empathy.

PMID- 17004560
TI  - Academy of General Dentistry. GD white paper on enteral conscious sedation.

PMID- 17004561
TI  - The top 50 prescription medications dispensed in pharmacies in 2005.

PMID- 17004562
TI  - Material choice for restorative dentistry: inlays, onlays, crowns, and bridges.
AB  - New materials--specifically the new CAD/CAM zirconia-based systems--are available
      now for restorative dentistry. When esthetics are not a factor, gold remains the
      standard, particularly for intracoronal restorations and full posterior coverage.
      Tooth-colored crowns made with zirconia are new and offer great promise for the
      future, although more long-term in vivo studies are necessary.

PMID- 17004563
TI  - Kinder and gentler, or the patient owns the enamel.

PMID- 17004564
TI  - Alternative treatments for resin-based composite and amalgam restorations with
      marginal defects: a 12-month clinical trial.
AB  - This clinical trial sought to evaluate the effectiveness of alternative treatment
      for replacing amalgam and resin-based composite restorations with marginal
      defects. The study recruited 66 patients with 271 restorations. Each restoration
      was assigned randomly to one of five groups: Sealant, Refurbishing, Repair,
      Replacement, and Untreated. Two clinicians evaluated the restorations according
      to USPHS/Ryge criteria at baseline (Kappa 0.74) and one year after the treatment
      (Kappa 0.81). The scoring of the margins improved (from bravo to alfa) after the
      experimental treatments. None of the treatments showed significant degradation of
      the margins during the 12-month observation period.

PMID- 17004565
TI  - Efficacy of propolis as an intracanal medicament against Enterococcus faecalis.
AB  - This study sought to compare the antibacterial efficacy of three commonly used
      intracanal medicaments with propolis against Enterococcus faecalis. This study
      utilized 180 freshly extracted single-rooted intact human permanent teeth with a
      single root canal. After root canal preparations and sterilization, canals were
      contaminated with E. faecalis and incubated at 37 degrees C (+/- 1.0 degrees C)
      for seven days. The teeth were divided randomly into six groups. To determine
      bacterial growth on blood agar, microbiological samples were carried out with
      sterile paper points to evaluate results at 48 hours and at ten days. All data
      were analyzed statistically with t-test, Mann Whitney, Kruskal Wallis, and one
      way ANOVA tests. This study revealed that propolis had good in vitro
      antibacterial activity against E. faecalis in the root canals, suggesting that it
      could be used as an alternative intracanal medicament.

PMID- 17004567
TI  - Composite matrix for large, non-wedgeable Class III or Class IV preparations with
      gingival or subgingival margins.
AB  - Dentists sometimes are required to place a matrix to restore large Class III or
      Class IV preparations that have gingival or subgingival margins or are prepared
      in rotated or malposed teeth. In these situations, dentists sometimes cannot
      place a wedge between the prepared tooth and a neighboring tooth because the
      wedge cannot engage enough interproximal tooth structure to firmly anchor both
      itself and a matrix strip. This article presents a technique for placing a matrix
      around such large, non-wedgeable Class III or Class IV preparations.

PMID- 17004566
TI  - Permeability of enamel following light-activated power bleaching.
AB  - This study sought to ascertain whether in-office photocured bleaching techniques
      would increase permeability to enamel. A 7.1 mm2 circular area located in the
      middle third of the coronal portion of 90 human canines was isolated by applying
      an acid-resistant varnish to the remaining surfaces of the tooth. According to a
      randomized complete block design (n = 15), specimens were treated using a 35%
      hydrogen peroxide bleaching product activated by an integrated LED/diode laser
      (LED/laser) source or a quartz tungsten halogen (QTH) light. Bleaching was
      accomplished by applying the 35% hydrogen peroxide agent to the enamel surface in
      three 10-minute sessions, conducted at one-week intervals over a period of three
      weeks. For the photocured bleached groups, a bleaching agent was applied to the
      specimen and irradiated with the LED/laser device or the QTH light for 30
      seconds. Negative control groups were exposed to artificial saliva or irradiated
      by the LED/laser device or the QTH light. Specimens were subjected to a
      histochemical coloring method that employed copper sulfate and dithio-oxamide
      solutions. Three 300-microm thick sections taken from the exposed area were
      imaged in an optical microscope. Permeability was measured in the digitized
      images as the percentage of copper ions penetration over the total enamel
      thickness. Friedman's test (alpha = 0.05) showed significant difference among
      groups. Least significant difference test revealed that in comparison with the
      group treated with 35% hydrogen peroxide only, there was no significant increase
      in enamel permeability when bleaching was activated by either the LED/laser or
      QTH light devices but all bleached groups showed higher permeability than the
      unbleached/nonirradiated group.

PMID- 17004568
TI  - Root canal anatomy illustrated by microcomputed tomography and clinical cases.
AB  - This study was designed to illustrate root anatomy by using microcomputed
      tomography and radiographs. Fresh human extracted teeth were selected randomly
      and prepared for scanning by a microscopic scanner. Each tooth was scanned at
      intervals of 0.9 degrees until it had been rotated 180 degrees. Data collected
      were used to generate cross-sectional images and three-dimensional tooth anatomy.
      Radiographs of completed endodontic cases that showed significant root canal
      anatomy also were collected and evaluated. Microcomputed tomographic scans showed
      that the main root canals branched out to finer branches and ended in multiple
      portals of exit. Intercommunication existed between the main and accessory
      canals. Apical exits of delta configuration were not common. Similar findings
      were evident in radiographs of the clinical cases. Both microcomputed tomographic
      scans and radiographs of completed clinical cases depicted similar complex root
      canal anatomy. This indicates that with an understanding of the anatomy, complex
      root canal systems can be cleaned, shaped, and obturated.

PMID- 17004569
TI  - A diagnostic challenge: anterior variant of mandibular lingual bone depression.
AB  - Mandibular lingual bone depressions are considered to be developmental anomalies
      and most clinicians are familiar with the posterior variant (known as Stafne's
      bone cavity) that occurs in lingual mandibular molar regions, adjacent to the
      submandibular gland and below the mandibular canal. The anterior variant of the
      mandibular lingual bone depression is an asymptomatic bone cavity that occurs
      adjacent to the sublingual gland in the anterior mandible. Radiographically, it
      appears as a well-corticated radiolucency that retains a normal trabecular
      pattern internally. CT imaging is diagnostic and avoids surgical and sialographic
      procedures. This article reviews radiographic and CT features of a case involving
      the anterior variant of mandibular lingual bone depression.

PMID- 17004570
TI  - Brown tumor of the mandible associated with secondary hyperparathyroidism: a case
      report and review of the literature.
AB  - Brown tumors are rare lesions that can develop in persistent cases of
      hyperparathyroidism (HPT). Therefore, identification of these lesions by
      diagnostic imaging is important during the follow-up of patients with HPT. This
      report describes a 45-year-old woman who developed HPT-induced brown tumors that
      appeared initially as an oral lesion. The diagnosis, treatment, and control of
      the disease--as well as the histopathological characteristics--are emphasized.

PMID- 17004571
TI  - Canine positioner.
AB  - This article describes a method for general dentists to treat impacted maxillary
      canines that are in a lingual position to achieve predictable results and
      minimize the number of office visits for the patient.

PMID- 17004572
TI  - Stainless steel crowns versus amalgams in the primary dentition and decision
      making in clinical practice.
AB  - This article reviews scientific dental literature related to amalgam restorations
      versus stainless steel crowns (SSCs) in the primary dentition. An extensive
      literature search of clinical studies was conducted to address the use of
      amalgams and SSCs in the primary dentition. The scientific literature provides
      evidence that SSCs demonstrate greater longevity and reduced need for
      retreatment, compared to multi-surface amalgam restorations. There is high-level
      evidence for the use of SSCs because of their cost-effectiveness, ease of
      placement, and longevity.

PMID- 17004573
TI  - A Cochrane systematic review finds tongue scrapers have short-term efficacy in
      controlling halitosis.
AB  - The Cochrane systematic review promotes evidence-based outcome studies. This
      review was conducted to determine reliable evidence concerning the effectiveness
      of tongue scraping or cleaning, compared with other interventions for controlling
      halitosis. A competent search strategy was developed and used across several
      databases--including the Cochrane Oral Health Group Trials Register, the Cochrane
      Central Register of Controlled Trials, MEDLINE, EMBASE, and Google Scholar--to
      identify randomized controlled trials that compared different methods of tongue
      cleaning to reduce mouth odor in adults with halitosis. Methodological quality of
      studies was assessed based on criteria defined by the Cochrane Collaboration.
      Clinical outcome (expressed in terms of a reduction in mouth odor in adults with
      halitosis) was examined. The review included two trials involving a total of 40
      participants. Based on the independent data from these two trials, the tongue
      cleaner or the tongue scraper demonstrated a statistically significant difference
      in reducing levels of volatile sulfur compounds (VSCs) when compared with the
      toothbrush. The findings indicate a small but statistically significant
      difference in reduction of VSC levels when tongue scrapers or cleaners, rather
      than toothbrushes, are used to reduce halitosis in adults.

PMID- 17004574
TI  - A qualitative assessment of dental care access and utilization among the older
      adult population in the United States.
AB  - This article presents an in-depth, qualitative assessment of the needs, issues,
      opportunities, and barriers concerning dental access and availability of oral
      care among older Americans. For the rapidly aging U.S. population, access and
      barriers to the provision of dental services were evaluated. The nature and types
      of services utilized by various segments of this population were examined and the
      attitudes, opinions, and perceptions of dental professionals regarding the
      delivery of services were analyzed. From this research, potential opportunities
      for strategic partnerships between organized dentistry and industry were
      developed. These collaborative partnerships will seek to improve access to oral
      health care for the fastest growing segment of the U.S. population.

PMID- 17004575
TI  - Sore mandible. Bisphosphonate-associated osteonecrosis.

PMID- 17004576
TI  - Sixty-minute contact hour to be implemented in 2007.

PMID- 17004579
TI  - Putting nurses in the driver's seat.

PMID- 17004581
TI  - Current concepts in joint replacement.

PMID- 17004580
TI  - Radiologic case study. Rheumatoid arthritis.

PMID- 17004583
TI  - The gender-specific (female) knee.

PMID- 17004582
TI  - Stabilization of osteotomies in children with developmental dislocated hip using
      external fixation.

PMID- 17004584
TI  - Treatment of perioperative blood loss.

PMID- 17004585
TI  - Current trends for the biological treatment of segmental bone loss in high-energy
      long bone fractures.

PMID- 17004586
TI  - Truth in advertising: the ethical limits of direct-to-consumer marketing.

PMID- 17004587
TI  - The economics of new age arthroplasty: can we afford it?

PMID- 17004588
TI  - Total hip arthroplasty after failed fixation of hip fractures.

PMID- 17004589
TI  - Intraoperative fractures during primary total hip arthroplasty.

PMID- 17004590
TI  - Periprosthetic fractures: a problem on the rise.

PMID- 17004591
TI  - Pathologic hip fractures: a class of their own.

PMID- 17004592
TI  - Cemented femoral fixation: a historical footnote.
AB  - Time will permit cemented stems to receive their proper footnote, as they have
      paved the way for uncemented stems, which are easier and more predictable to
      implant. Uncemented stems can be used for all occasions and by all surgeons, are
      available in many geometries and designs, and have proven durability in longterm
      studies. In addition, once uncemented stems are stable, they are unlikely to
      loosen.

PMID- 17004593
TI  - Cemented or cementless stem fixation in THA: what is the current evidence?

PMID- 17004594
TI  - Metal-on-metal hip resurfacing: America, where are you?

PMID- 17004595
TI  - Postoperative wound infection: 35 years of experience.

PMID- 17004596
TI  - Infected hip arthroplasty: "maximizing its solution: once burned, twice learned".

PMID- 17004598
TI  - The modular neck: keystone to functional restoration.

PMID- 17004597
TI  - Blood management in joint replacement surgery: what's in and what's out.

PMID- 17004599
TI  - Femoral deformity correction: sometimes, always, never.

PMID- 17004600
TI  - Threaded acetabular cups: results inferior to cemented and ingrowth sockets.
      Point.

PMID- 17004601
TI  - Redesigned threaded, double-cone titanium cups yield excellent mid-term results.
      Counterpoint.

PMID- 17004602
TI  - Cemented femoral stem revision: is there still a role?

PMID- 17004603
TI  - Proximal femur impaction grafting: when half a loaf will do.

PMID- 17004604
TI  - Proximal fixation with a modular stem in complex revision THA.

PMID- 17004605
TI  - The role of modular femoral components: distal fixation.

PMID- 17004606
TI  - Resection arthroplasty: when enough is enough.
AB  - Resection arthroplasty following THA is rarely performed but occasionally
      indicated. It is a relatively low risk procedure and generally is a much shorter
      operative procedure associated with fewer perioperative complications compared to
      major revision procedures. Results are extremely variable. With all of the
      arthroplasty and bone graft options available for hip joint reconstruction,
      resection arthroplasty rarely is performed as a definitive procedure. It is,
      however, the best option for selected patients.

PMID- 17004607
TI  - The injectables: palliation and promise.

PMID- 17004608
TI  - The lateral unicompartmental replacement: a road less traveled.

PMID- 17004609
TI  - Mobile magic: try it, you'll like it.
AB  - Mobility affords conformity that results in less polyethylene stress and perhaps
      less load on the underlying bone. Wear has been documented to be less. There are
      excellent long-term data on large numbers of patients, and I would submit that if
      you try it, both you and your patients will love it.

PMID- 17004610
TI  - Three decades of experience with unicompartmental knee arthroplasty: mistakes
      made and lessons learned.
AB  - Unicompartmental arthroplasty results and survivorship will continue to improve
      with time. The future will refine patient selection and bring better surgical
      techniques and prosthetic designs. Improved polyethylene will increase longevity
      of the arthroplasty, and mobile-bearing articulations also may improve longevity
      by decreasing wear and allowing a metal-backed component with relatively thin
      polyethylene inserts for a conservative arthroplasty.

PMID- 17004611
TI  - The role of patellar resurfacing in TKA. Point.
AB  - While controversy persists, scientific evidence favoring patellar resurfacing in
      primary TKA is abundant. The literature demonstrates a substantially higher
      incidence of anterior knee pain and reoperation rates if the patella is not
      resurfaced primarily. Prospective, randomized studies have reported reoperation
      rates to convert unresurfaced patellas to resurfaced patellas exceed those for
      complications after patellar resurfacing. When resurfacing the patella, strict
      surgical principles are paramount to avoid complications. These include
      duplicating the original patella thickness, maintaining the patellar blood
      supply, achieving central patellar tracking, and properly positioning the
      femoral, tibial, and patellar components. Optimum prosthetic design features for
      patella resurfacing include an anatomic, asymmetric trochlear groove that is
      broad, extended, (distally and posteriorly) and deeper compared with first
      generation designs.

PMID- 17004613
TI  - Sex and the total knee: gender-sensitive designs.

PMID- 17004612
TI  - Patella resurfacing no longer considered routine in TKA. Counterpoint.

PMID- 17004614
TI  - Which implant do I pick? A glossary of promises.

PMID- 17004615
TI  - Why knees fail: a tutorial.

PMID- 17004616
TI  - Preoperative planning for revision TKA: where do you want to go today?

PMID- 17004617
TI  - The role of implant constraint in revision TKA: striking the balance.

PMID- 17004618
TI  - Augments and void fillers: metallica.

PMID- 17004619
TI  - Revision TKA: four cases that taught me new things.

PMID- 17004620
TI  - Patterns of childhood cancer in Hawai'i between 1975 and 2000.
AB  - This study investigated the 25-year incidence of childhood cancer in Hawai'i,
      including sex, age, and ethnic differences and time trends. Leukemia was the most
      common diagnosis. Japanese in Hawai'i have lower pediatric cancer rates than for
      the United States. Previous trends toward increasing ethnic disparities in
      incidence rates were not found. Growing numbers of survivors imply the need for
      increased follow-up care.

PMID- 17004621
TI  - Variations in clinical practice among the Hawaiian islands.
AB  - State health surveys and hospital discharge data suggest aspects of health care
      may vary by island in the state of Hawai'i. This study further examines the issue
      comparing O'ahu, Maui, Hawai'i, and Kaua'i on 15 indicators of recommended
      clinical care using data from a large insurer in Hawaii. The Hawaiian Islands
      differed to a statistically significant extent on 14 of the 15 indicators. O'ahu
      had the highest percentage of recommended care for six indicators, Maui for four,
      Kaua'i for three, and Hawai'i for two. In analyses adjusted for age, gender,
      morbidity, and health plan--and comparing the outer islands individually to O'ahu
      -O'ahu had more favorable care in 16 of 18 statistically significant comparisons.
      More focused geographic studies may be warranted to clarify where and why the
      variations in health care occur.

PMID- 17004622
TI  - Adolescent calorie/fat menu ordering at fast food restaurants compared to other
      restaurants.
AB  - OBJECTIVE: Childhood and adolescent obesity is an increasing public health
      problem. Fast food consumption has been linked to obesity. The purpose of this
      study is to determine adolescent calorie and fat consumption patterns at
      different types of restaurants. METHOD: Study subjects (104 adolescents) were
      asked to order a dinner meal from 10 restaurant menus with an estimate of how
      much they would actually consume. A paired T-test was used to compare the
      calories and fat values for each restaurant vs. McDonald's. RESULTS: Mean
      calories/fat (g) ordered at each restaurant were: California Pizza Kitchen
      (CPK).: 1284/70, Chili's (Ch). 1333/62, Denny's (Den): 1226/61, McDonald's (MD):
      1016/45, Outback Steakhouse (OS): 1656/93, Panda Express (PE): 873/29, Red
      Lobster (RL): 1016/49, Stuart Anderson's (SA). 1058/52, Taco Bell (TB): 800/34,
      Wendy's (Wen): 879/32. Calorie/fat content of the ordered items were
      significantly higher at CPK, Ch, Den, and OS compared to McDonald's. RL and SA
      were not significantly different from MD. Calorie/fat content of the ordered
      items were significantly lower at PE, TB and Wen compared with McDonald's.
      CONCLUSION: More calories/fat were ordered at many sit down restaurants compared
      to McDonald's. The lowest calories/fat were ordered at other fast food
      restaurants (Taco Bell, Wendy's and Panda Express).

PMID- 17004623
TI  - The role of public health in medical education.

PMID- 17004624
TI  - Selenium, selenoproteins, and cancer.

PMID- 17004625
TI  - Issues in medical malpractice II.

PMID- 17004626
TI  - The survival of freely grafted orbital fat on porous polyethylene orbital
      implants in the rabbit.
AB  - PURPOSE: To investigate the long term survival of orbital fat grafted on a Medpor
      implant as a method of preventing porous polyethylene orbital implant (Medpor)
      exposure in anophthalmic sockets. METHODS: In one orbit in each of 8 rabbits, a
      small amount of retrobulbar orbital fat was grafted between the anterior surface
      of the Medpor implant and overlying conjunctiva, during the enucleation and
      Medpor implantation procedure. Two rabbits were sacrificed at 2, 4, 8 and 12
      weeks postoperatively and grafted orbital fats were examined by light microscopy.
      RESULTS: Grafted orbital fat was well-maintained at 2 and 4 weeks,
      postoperatively. However, fat amounts were significantly reduced at 8 weeks, and
      viable fat was barely visible at 12 weeks. CONCLUSIONS: In rabbits, orbital fat
      grafted on Medpor implants was gradually resorbed, and the fat-occupied volume
      was not maintained.

PMID- 17004627
TI  - A phacovitrectomy with a clear corneal incision for a full-thickness macular
      hole.
AB  - PURPOSE: To describe the results of a pars plana vitrectomy, combined with
      phacoemulsification, using a sutureless, superotemporal, clear corneal incision
      for patients with a macular hole. METHODS: This study reviewed the records of 22
      patients (22 eyes) who underwent a phacoemulsification with the insertion of an
      acrylic intraocular lens, using a 3.2 mm superotemporal clear corneal incision
      and a pars plana vitrectomy with an internal limiting membrane peeling in one
      session, for the treatment of a macular hole. RESULTS: All 22 patients had their
      macular holes closed using the combined surgical procedures. The mean
      preoperative visual acuity was 0.086, and the mean postoperative visual acuity
      was 0.173. This improvement was statistically significant (paired Student's t
      test, p < 0.05). No patients developed posterior capsular opacity, retinal
      detachment, or a cystoid macular edema. The surgically induced astigmatism (SIA)
      was 0.808 diopters (0.808 +/- 0.761) two months after surgery. CONCLUSIONS:
      Combining cataract surgery with vitrectomy can achieve visual rehabilitation in
      the early postoperative period without requiring post-vitrectomy cataract
      surgery. A sutureless clear corneal incision, used in this procedure, can
      minimize the SIA and promote postoperative wound healing. If sutureless,
      transconjunctival, pars plana vitrectomy can be used more widely in the future,
      then the simplified, combined cataract surgery using a small clear corneal
      incision will also become more common, hence decreasing operation time, and
      hastening postoperative recovery.

PMID- 17004628
TI  - Posterior chamber intraocular lens implantation in pediatric cataract with
      microcornea and/or microphthalmos.
AB  - PURPOSE: To report the results of secondary posterior chamber intraocular lens
      (PC-IOL) implantation in pediatric cataract eyes with microcornea and/or
      microphthalmos. METHODS: Retrospective studies were conducted by reviewing the
      charts of 26 eyes of 15 patients with secondary PC-IOL implantations for
      microcornea and/or microphthalmos associated with cataract in children between
      1999 and 2002. The corneal diameter was 9.5 mm or less at the time of secondary
      PC-IOL implantation. Preoperative examinations were conducted for bilaterality,
      corneal diameter, eye abnormalities and systemic abnormalities. Postoperative
      results were evaluated in terms of visual developments, refractive changes, axial
      length measurements and the occurrence of complications. The follow-up period was
      at least one year after secondary PC-IOL implantation. RESULTS: Age at the first
      diagnosis for cataract with microcornea and/or microphthalmos was 2.7 months on
      average. Among 15 patients, 8 (53.3%) had a family history. All patients received
      an initial irrigation and aspiration, posterior capsulectomy, and anterior
      vitrectomy at 0.8 years (0.1-3.3 years) of age and a secondary PC-IOL
      implantation surgery at 6.7 years (1.6-17.2 years) of age on average. The
      postoperative follow-up period was 2.1 years (1.1-4.3 years) on average. The
      average power of the implanted PC-IOL was +21.2D. Postoperative complications
      were secondary glaucoma in two eyes, secondary pupillary membrane formation in
      two eyes. Best corrected visual acuities in 20 eyes in children capable of the
      vision test at the last follow-up were 20/60 or better in 11 eyes, 20/80 to
      20/150 in eight eyes, and 20/200 or worse in one eye. CONCLUSIONS: The secondary
      PC-IOL implantation in pediatric cataract with microcornea and/or microphthalmos
      is recommended as a means of improving vision, but must be conducted carefully to
      avoid possible complications.

PMID- 17004629
TI  - Intravitreal triamcinolone reinjection for refractory diabetic macular edema.
AB  - PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide (IVT)
      reinjection on clinical and optical coherence tomographic features in refractory
      diabetic macular edema. METHODS: In a prospective interventional case series, all
      IVT treated patients enrolled in a previous clinical trial were recalled to have
      a new ophthalmologic examination and optical coherence tomography (OCT)
      performed. Eyes found suitable for reinjection received 4 mg IVT. Complete
      clinical examination and OCT were repeated at 2 and 4 months post-injection. The
      changes were statistically analyzed using a paired t test and were compared to
      the results of the first injections. RESULTS: Of all returning patients, 12 cases
      with complete records were considered candidates for reinjection. Visual acuity
      (VA) changes were not significant after the first and second interventions,
      although there was a relative improvement (0.14 logMAR) 2 months after the first
      injection. Reductions of central macular thickness (CMT) were 43 +/- 69 microm,
      and 40 +/- 69 microm after the first injection and 27 +/- 48 microm, 49 +/- 58
      microm after the reinjection at 2 & 4 months, respectively. None of the mentioned
      changes was significant. After the second injection, however, intraocular
      pressure was elevated at both 2 & 4 months (3.6 & 2.4 mmHg respectively, P <
      0.05). Two months after the first administration, intraocular pressure was found
      to be raised significantly (5.58 mmHg, P = 0.001). CONCLUSIONS: The transient
      beneficial effects of IVT on diabetic macular edema are not repeated with second
      injections. However, IVT-related ocular hypertension is more persistent after
      reinjection. Korean

PMID- 17004630
TI  - Transforming growth factor-beta levels in human aqueous humor of glaucomatous,
      diabetic and uveitic eyes.
AB  - PURPOSE: Transforming growth factor-beta2 is known to be present at elevated
      levels in the aqueous humor of patients with primary open angle glaucoma (POAG)
      and diabetes but not in uveitis-related secondary glaucoma. We investigated total
      TGF-beta2 levels and levels of the active form of TGF-beta2 in the aqueous humor
      of eyes with different types of glaucoma. METHODS: The concentration of the total
      and active form of TGF-beta2 was measured in 63 patients with primary open angle
      glaucoma, neovascular glaucoma complicated with diabetes (NVG), and secondary
      open angle glaucoma complicated with uveitis (SOAG) using a double antibody
      'sandwich-indirect' ELISA method. RESULTS: The levels of total TGF-beta2 in the
      aqueous samples of POAG, NVG, and SOAG were elevated. The levels of active TGF
      beta2 in the aqueous samples of POAG, and NVG were also elevated, whereas the
      level of active TGF-beta2 was within the normal range in the aqueous samples of
      SOAG. CONCLUSIONS: These results suggest that the level of TGF-beta2 may play a
      role in the pathology of various types of glaucoma.

PMID- 17004631
TI  - Ocular hypertensive response to topical dexamethasone ointment in children.
AB  - PURPOSE: To investigate the rate and the degree of the ocular hypertensive
      response to dexamethasone ointment in children undergoing eyelid surgery.
      METHODS: Dexamethasone ointment (Dexcosil) was applied three times a day for the
      first week and twice a day for the second to third week postoperatively to
      children undergoing epiblepharon surgery. Intraocular pressure (lOP) was measured
      on the day before surgery, postoperative day 1, 7, 14, 21, 28 and 2 weeks
      thereafter until the IOP reached preoperative levels. Peak IOP, IOP net increase
      and time to reach a peak IOP were analyzed. Dexamethasone ointment was
      discontinued if the IOP was 25 mmHg or more. RESULTS: A total of 96 children
      (mean age, 6.5 +/- 2.7 years) were included. Preoperative mean IOP was 13.6 +/-
      2.9 mmHg (range 7-19). After dexamethasone ointment treatment, the children
      showed a significant rise in IOP as compared with the preoperative values. The
      peak IOP was 20.6 +/- 4.9 mmHg (range 11-39) and the time to reach peak IOP was
      8.5 +/- 5.9 days. The low responders (delta IOP < or = 5 mmHg) of our group
      comprised 35.4% (34/96) of patients, intermediate responders (delta IOP 6-15
      mmHg) comprised 56.3% (54/96) of patients and high responders (delta IOP > or
      =16) comprised 8.3% (8/96) of patients. A net increase in IOP was significantly
      higher in children 5 years old or less as compared with those older than 5 years
      (age < or =5, 9.4 +/- 7.5 mmHg vs. age > 5, 6.3 +/- 4.4 mmHg; p = 0.015, unpaired
      t-test). CONCLUSIONS: Ocular hypertensive response after dexamethasone ointment
      to the eyelids occurred frequently in children, especially those 5 years old or
      younger.

PMID- 17004632
TI  - Part-time occlusion therapy for anisometropic amblyopia detected in children
      eight years of age and older.
AB  - PURPOSE: To determine the outcome of part-time occlusion therapy in children with
      anisometropic amblyopia detected after they were 8 years of age. METHODS: We
      analyzed 29 eyes with anisometropic amblyopia in children 8 years of age and
      older. The mean age was 8.79 +/- 0.98 (range 8-12) years old. The subjects whose
      best-corrected visual acuity (BCVA) did not improve by two lines or better within
      2 weeks of wearing glasses full-time were prescribed occlusion therapy for 6
      hours a day outside of school hours, along with the instruction to wear glasses
      full-time. Subjects who complied with occlusion for more than 3 hours a day were
      considered to comply well. RESULTS: The major component of the anisometropia was
      hyperopia in 51.7% of the subjects, and hyperopia plus astigmatism was found in
      24.1%. The mean pretreatment BCVA score was 0.51 0.23 (LogMAR). Compliance was
      89.66%. The mean posttreatment BCVA was 0.03 +/- 0.01 (LogMAR), and the success
      rate, based on a posttreatment BCVA of 0.1 (LogMAR) and better, was 96.43%. It
      took an average of 4.79 +/- 3.35 months to reach the desired posttreatment BCVA.
      The mean posttreatment stereopsis was 79.78 +/- 37.61 seconds of arc. The
      recurrence rate was 8%. The visual improvement was related to the degree of
      compliance (p = 0.000). The time taken to reach the posttreatment BCVA was
      shorter in subjects with a better pretreatment BCVA (p = 0.019), but it did not
      relate to the compliance (p = 0.366). CONCLUSIONS: The most common component of
      anisometropia detected after 8 years of age was hyperopia. The part-time
      occlusion therapy, which had been carried out after school hours, was successful
      in most cases.

PMID- 17004633
TI  - Thicknesses of the fovea and retinal nerve fiber layer in amblyopic and normal
      eyes in children.
AB  - PURPOSE: This study was designed to assess and compare the thicknesses of the
      fovea and the retinal nerve fiber layer in normal children and children with
      amblyopia. METHODS: Optical Coherence Tomography (OCT) was performed on 26
      children (52 eyes total) with unilateral amblyopia that was due to anisometropia
      or strabismus. OCT was also performed on 42 normal children (84 eyes), for a
      total of 136 eyes. Retinal thickness measurements were taken from the fovea, and
      the retinal nerve fiber layer thickness measurements were taken from the
      superior, inferior, nasal and temporal quadrants in the peripapillary region.
      RESULTS: The average age of the normal children was 8.5 years, and the average
      age of the children with amblyopia was 8.0 years. The average thickness of the
      fovea was 157.4 microm in normal eyes and was 158.8 microm in amblyopic eyes. The
      difference between the two groups was not statistically significant (p = 0.551).
      The thicknesses of the superior, inferior, nasal and temporal quadrants of the
      retinal nerve fiber layer between the normal children and the children with
      amblyopia were also not statistically significant (p = 0.751, 0.228, 0.696 and
      0.228, respectively). However, for the children with anisometropic amblyopia and
      the children with strabismic amblyopia, the average thicknesses of the fovea were
      146.5 microm and 173.1 microm, respectively, and the retinal nerve fiber layer
      thicknesses were measured to be 112.9 microm and 92.8 microm, respectively, and
      these were statistically significant differences (p = 0.046, 0.034,
      respectively). CONCLUSIONS: Normal thicknesses of the fovea and the retinal nerve
      fiber layers were established, and there were no differences in the fovea and the
      retinal nerve fiber layer thickness found between normal children and children
      with amblyopia.

PMID- 17004634
TI  - Clinical study for the undercorrection factor in intermittent exotropia.
AB  - PURPOSE: The surgical technique for intermittent exotropia [X(T)] is quite
      simple. However, in many cases, the condition recurs due to any one of a number
      of causes, including undercorrection. This study examined the factors associated
      with undercorrection on X(T) patients. METHODS: The study examined 199 X(T)
      patients who underwent bilateral recession of the lateral rectus muscle or
      unilateral recession of the lateral rectus muscle and resection of the medial
      rectus muscle, and who were followed-up for more than a year. Patients whose near
      and far distance angles of deviation were 9 prism diopters (PD) or more at one
      year after surgery were designated as group 1. Those whose PD was 8 or below or
      who had orthophoria were assigned to group 2. Various factors were compared and
      analyzed. RESULTS: One day after surgery, group 1 showed an average
      overcorrection of 1.9 and 4.1 PD at near and far, respectively, and group 2
      showed an average overcorrection of 6.3 and 7.6 PD at near and far, respectively.
      A statistically significant difference was observed between the two groups (p <
      0.05). Factors such as the age of onset of strabismus, age at the time of
      surgery, the interval from the onset of strabismus to surgery, the preoperative
      angle of deviation, the dissociated vertical deviation, amblyopia, anisometropia
      and vertical strabismus had no influence on the undercorrection of X(T) patients
      (p > 0.05). CONCLUSIONS: Of the many factors that might influence the surgical
      results of X(T) patients, the angle of deviation during the initial postoperative
      period is the most important factor.

PMID- 17004635
TI  - The effect of graded recession and anteriorization on unilateral superior oblique
      palsy.
AB  - PURPOSE: We wanted to examine the effect of graded recession and anteriorization
      of the inferior oblique muscle on patients suffering from unilateral superior
      oblique palsy. METHODS: Inferior oblique muscle graded recession and
      anteriorization were performed on twenty-two patients (22 eyes) with unilateral
      superior oblique palsy. The recession and anteriorization were matched to the
      degree of inferior oblique overaction and hypertropia. The inferior oblique
      muscle was attached 4 mm posterior to the temporal border of the inferior rectus
      muscle in six eyes, 3 mm posterior in five eyes, 2 mm posterior in five eyes, 1
      mm posterior in five eyes, and parallel to the temporal border in one eye.
      RESULTS: The average angle of vertical deviation prior to surgery was 11.3 +/-
      3.9 prism diopters (PD). The total average correction in the angle of vertical
      deviation after surgery was 10.8 +/- 3.8 PD. In the parallel group, the average
      reduction was 14 PD. After surgery, normal inferior oblique muscle action was
      seen in eighteen of twenty-two eyes (81.8%). CONCLUSIONS: Graded recession and
      anteriorization of the inferior oblique muscle is thought to be an effective
      surgical method to treat unilateral superior oblique palsy of less than 15 PD.

PMID- 17004636
TI  - T-cell lymphoma presenting as painful ophthalmoplegia.
AB  - PURPOSE: To present a case of peripheral T-cell lymphoma presenting as painful
      ophthalmoplegia. METHODS: A 61-year-old woman presented with a 2-week history of
      headache and eyeball pain. Examination showed mild exophthalmos, complete
      ophthalmoplegia, and ptosis of the left eye. Under the impression of nonspecific
      orbital inflammation, she was treated with oral prednisone with initial response.
      Two months later, she revisited the clinic with exacerbated symptoms. Anterior
      orbitotomy and incisional biopsy was performed for the inferior rectus muscle
      lesion. RESULTS: Histopathologic examination revealed an infiltrate of atypical
      lymphoid cells between degenerative muscle bundles. It was consistent with
      peripheral T-cell lymphoma. A metastatic workup was performed without any
      evidence of extraorbital tumor. The patient was recommended to be treated with
      chemotherapy, however, refused to take the treatment. The patient died of
      progression of the disease in a month. CONCLUSIONS: T-cell lymphoma in the orbit
      can present as painful ophthalmoplegia and take a rapid clinical course. The
      disease should be regarded as one of the differential diagnosis for painful
      ophthalmoplegia refractory to corticosteroid therapy.

PMID- 17004637
TI  - A case of intramuscular hemangioma presenting with large-angle hypertropia.
AB  - PURPOSE: To report the case of a patient with large-angle hypertropia of an
      intramuscular hemangioma of the right superior rectus muscle (SR). METHODS: A 63
      year-old man with progressive vertical deviation of the right eye for the past 6
      months visited our strabismus department; his condition was not painful. An
      examination indicated that he had 60PD of right hypertropia at distance and near
      in primary gaze. Additionally, a significant limitation of his downgaze was
      noted. The right eye appeared mildly proptotic, and the upper and lower eyelids
      were slightly edematous. Corrected vision was 20/20 in both eyes. RESULTS:
      Orbital magnetic resonance imaging (MRI) studies revealed fusiform enlargement of
      the right superior rectus muscle, with prominent but irregular enhancement
      following gadolinium administration. Incisional biopsy revealed an intramuscular
      hemangioma in the superior rectus muscle with cavernous-type vessels.
      CONCLUSIONS: This case demonstrates that intramuscular hemangioma should be
      considered in the differential diagnosis of isolated extraocular muscle
      enlargement and unusual strabismus.

PMID- 17004639
TI  - Big digs are not just in Boston--the need for government oversight.

PMID- 17004638
TI  - Inadvertent ocular perforation during lid anesthesia for hordeolum removal.
AB  - PURPOSE: Ocular perforation during lid anesthesia is rarely reported. We describe
      here a case of inadvertent corneal perforation and traumatic cataract that
      occurred during lid anesthesia in a procedure for hordeolum removal. METHODS: A
      33-year-old woman presented with a sudden visual loss of her left eye. She had
      undergone hordeolum removal the day before at a local clinic. On ophthalmologic
      examination, the cornea was perforated and the lens cortex was extruded into the
      anterior chamber. After cataract removal and IOL implantation, antibiotics were
      injected into the vitreous. RESULTS: Her final visual acuity of the left eye was
      20/20. Postoperative specular microscopic examination revealed a normal-range
      endothelial cell count, coefficient of variation, and hexagonality despite the
      intracameral lidocaine injection. CONCLUSIONS: Anesthetic injection of an
      infected lid should be done with great caution. Although there are possibilities
      of corneal endothelial toxicity and endophthalmitis in case of intracameral
      lidocaine injection through the infected lid, yet proper management may save the
      patient's vision without complications.

PMID- 17004640
TI  - Survival skills for the political environment of health insurance.
AB  - Blue Cross Blue Shield of Michigan asked the Michigan state government for small
      group market rate reform already adopted in most other states. Officials
      responded with major restructuring proposals aimed specifically at the Blues. The
      Michigan Blues fought back with a massive lobbying campaign as vigorous as any
      mounted by opponents of health reform at the national level. The company was able
      to prevail over one of the most powerful governors in Michigan history, whose
      party controlled both houses of the legislature. This amazing political victory
      shared much in common with the Clinton health reform's defeat by the industry and
      the more recent success of the prescription drug industry in shaping Medicare
      prescription drug reform to its liking. The experience suggests that political
      savvy and lobbying skills have become core competencies in the health care
      industry.

PMID- 17004641
TI  - Toward universal coverage in Massachusetts.
AB  - This paper presents several options designed to help the Commonwealth of
      Massachusetts move to universal health insurance coverage. The alternatives all
      build upon a common base that includes an expansion of the Medicaid program,
      income-related tax credits, a purchasing pool, and government-sponsored
      reinsurance. These measures in themselves would not yield universal coverage, nor
      would an employer mandate by itself. We show that an individual mandate, and an
      employer mandate combined with an individual mandate, both would yield universal
      coverage with a relatively small increase in government costs relative to state
      gross domestic product and current health spending. The cost of an employer
      mandate--with a "pay or play" design--is sensitive to the payroll tax rate and
      base, the number and kind of exemptions, and whether workers whose employers
      "pay" receive discounts when they purchase health insurance. The development of
      these alternatives and their analyses contributed to the eventual health care
      compromise that emerged in Massachusetts in April 2006.

PMID- 17004642
TI  - Price and the demand for nongroup health insurance.
AB  - In light of recent interest in tax credits and other price-based incentives to
      stimulate the purchase of insurance, this study estimates the price elasticity of
      demand for nongroup health insurance for single workers without access to
      employer-sponsored insurance. Our premium measure explicitly accounts for two
      components that have not been examined in previous studies: 1) health status, and
      2) the effect of state-level premium rating regulations. We estimate a price
      elasticity of -.59, which, given the low rate of initial coverage in our sample
      (16.4%), translates to a small effect on the uninsured.

PMID- 17004643
TI  - The influence of Medicare home health payment incentives: does payer source
      matter?
AB  - During the late 1990s, the U.S. government instituted an interim payment system
      (IPS) to constrain Medicare home health care expenditures. Previous research has
      focused largely on the implications of the IPS for Medicare patients; this study
      broadens the analysis to consider patients with other payer sources. Using the
      National Home and Hospice Care Survey, we found similar effects of the IPS across
      payer types. Specifically, the IPS was associated with a decrease in care for the
      sickest patients, less agency assistance with activities of daily living, and
      shorter length of use. However, these changes did not translate into worse
      discharge outcomes.

PMID- 17004645
TI  - On the feasibility of resolving the organ shortage.
AB  - Debates concerning the feasibility of resolving the organ shortage from the
      potential pool of deceased donors have suffered from both conceptual and
      empirical problems. Conceptually, several authors mistakenly have viewed
      recipient waiting lists as a measure of the magnitude of the shortage. And
      empirically, the number of deaths that would qualify for potential organ donation
      has proven difficult to estimate. While the latter problem appears to have been
      substantially lessened by recent work, the former, definitional, problem remains.
      This paper offers the economically correct definition of a shortage and applies
      that definition to the new data on potential supply.

PMID- 17004644
TI  - Do report cards influence hospital choice? The case of kidney transplantation.
AB  - The national program to report hospital-level outcomes for transplantation has
      been in place since 1991, yet it has not been addressed in the existing
      literature on hospital report cards. We study the impact of reported outcomes on
      demand at kidney transplant centers. Using a negative binomial regression with
      hospital fixed effects, we estimate the number of patients choosing each center
      as a function of reported outcomes. Parameters are identified by the within
      hospital variation in outcomes over five successive report cards. We find some
      evidence that report cards influence younger and college-educated patients, but,
      overall, report cards do not affect demand.

PMID- 17004646
TI  - Access to health care after welfare reform.
AB  - This research uses data from a longitudinal statewide study of Oregon families
      leaving Temporary Assistance to Needy Families (TANF) to identify: 1) the trends
      in insurance coverage over time; 2) the role of health insurance coverage in
      predicting whether respondents received needed medical care; and 3) the
      relationship between access to care and physical and mental health. Data were
      obtained from 637 families seven months after leaving welfare for work; 552 of
      these families were re-interviewed one year later. The data reveal that 40% of
      TANF leavers were uninsured at wave 2 and suggest that significant access
      barriers exist, which may be associated with poor health outcomes.

PMID- 17004647
TI  - Metabolites produced by cyanobacteria belonging to several species of the family
      Nostocaceae.
AB  - This paper provides a comprehensive overview of metabolites, including lipids and
      lipid-like compounds, nitrogen metabolites, oligopeptides and amino acid
      derivatives, produced by cyanobacteria of the genera Anabaenopsis, Aphanizomenon,
      Aulosira, Cylindrospermopsis, Cylindrospermum, Nodularia, and Richelia of the
      family Nostocaceae.

PMID- 17004648
TI  - Demonstration of the shorter flagellin (flaA) gene of urease-positive
      thermophilic Campylobacter isolated from the natural environment in Northern
      Ireland.
AB  - The PCR amplicons (about 1450 bp in length) of flaA gene fragments of 11 isolates
      of urease-positive thermophilic Campylobacter (UPTC) isolated from the natural
      environment not including wild birds in Northern Ireland were demonstrated to be
      shorter than those of C. jejuni 81116 and six isolates of C. jejuni and C. coli
      (about 1700 bp) isolated in Northern Ireland and Japan. When the nucleotide
      lengths of the possible open reading frame (ORF) of the flaA genes were
      determined, those from the 11 UPTC isolates were estimated to be 1464-1503 bp,
      and those from the six C. jejuni and C. coli isolates and C. jejuni 81116 strain
      to be 1716-1728 bp. Nucleotide sequence and deduced amino acid sequence
      alignments of the possible ORFs demonstrated that the ORFs from the 11 UPTC
      isolates lack about 80 amino acid residues, mainly from the approximate residue
      numbers 390-470 of the large variable region in the flaA protein of the seven
      isolates of C. jejuni and C. coli, and do not have any internal termination
      codons. High amino acid sequence similarity of both amino- and carboxy-termini of
      the ORFs of the flaA gene was demonstrated between the 11 isolates of UPTC and
      the 7 isolates of C. jejuni and C. coli. The 11 UPTC isolates examined were
      strongly suggested to possess a shorter flaA gene without any internal
      termination codons.

PMID- 17004649
TI  - Simultaneous production of sphingolipids and ethanol by Kluyveromyces
      thermotolerans.
AB  - Kluyveromyces thermotolerans strain NBRC 1674 was selected for the simultaneous
      production of sphingolipids and ethanol from beet molasses. The strain gradually
      synthesized ethanol with fermentation periods and attained a level slightly
      higher than that of the strain of Saccharomyces cerevisiae usually used for
      ethanol production. The sphingolipids accumulated in the cells were composed of
      almost equal amounts of free ceramides and glucosylceramides. The sphingoid bases
      and fatty acids of the two sphingolipids differed from each other and changed
      under aerobic and anaerobic growth conditions. Oxygen limitation may cause
      accumulation of sphinganine by inhibiting sphingolipid desaturases and enhance
      its proportion in both the sphingolipids.

PMID- 17004650
TI  - Immunity to killer toxin K1 is connected with the Golgi-to-vacuole protein
      degradation pathway.
AB  - Killer strains of Saccharomyces cerevisiae producing killer toxin K1 kill
      sensitive cells but are resistant to their own toxin. It is assumed that in the
      producer, an effective interaction between the external toxin and its plasma
      membrane receptor or the final effector is not possible on the grounds of a
      conformation change of the receptor or its absence in a membrane. Therefore, it
      is possible that some mutants with defects in intracellular protein transport and
      degradation can show a suicidal phenotype during K1 toxin production. We have
      examined these mutants in a collection of S. cerevisiae strains with deletions in
      various genes transformed by the pYX213+M1 vector carrying cDNA coding for the K1
      toxin under the control of the GAL1 promoter. Determination of the quantity of
      dead cells in colony population showed that (1) the toxin production from the
      vector did not support full immunity of producing cells, (2) the suicidal
      phenotype was not connected with a defect in endocytosis or autophagy, (3)
      deletants in genes VPS1, VPS23, VPS51 and VAC8 required for the protein
      degradation pathway between the Golgi body and the vacuole exhibited the highest
      mortality. These results suggest that interacting molecule(s) on the plasma
      membrane in the producer might be diverted from the secretion pathway to
      degradation in the vacuole.

PMID- 17004652
TI  - Conidiation of Trichoderma atroviride isolate during submerged cultivation in a
      laboratory stirred-tank fermenter.
AB  - Conditions for conidiation of a natural isolate of Trichoderma atroviride during
      submerged cultivation in Erlenmeyer flasks and in a laboratory stirred-tank
      fermenter were optimized. From the simple sugars tested, cellobiose was the best
      substrate for conidia production while cellulose fines from paper mill waste
      proved to be a suitable cheap complex carbon source. Optimum temperature for
      conidiation was 24-26 degrees C, and the required dissolved oxygen level was >
      40% saturation. After initial slight decrease during the 1st d after inoculation,
      the pH of the culture medium constantly increased throughout the sporulation
      period. Attempts to regulate the pH during fermentation did not improve the spore
      yields. The most intense formation of conidia took place between 2nd and 3rd d of
      growth and the overall volumetric productivity of conidia was 4.1-8.2 x 10(9)
      conidia per L/h.

PMID- 17004651
TI  - Expression of the Saccharomyces cerevisiae MPR1 gene encoding N-acetyltransferase
      in Zygosaccharomyces rouxii confers resistance to L-azetidine-2-carboxylate.
AB  - The osmotolerant yeast Zygosaccharomyces rouxii is sensitive to the toxic L
      proline analogue, L-azetidine-2-carboxylate (AZC). The possibility of use of the
      Saccharomyces cerevisiae MPR1 gene (ScMPR1) encoding the AZC-detoxifying enzyme
      as a dominant selection marker in Z. rouxii was examined. The heterologous
      expression of ScMPR1 in two Z. rouxii strains resulted in AZC-resistant colonies,
      but that of ScMPR1 as a dominant marker gene in vectors was affected by a high
      frequency of spontaneously resistant colonies. The same was found for an AZC
      sensitive S. cerevisiae strain in which the ScMPR1 was expressed. In both yeasts,
      ScMPR1 can be used only as an auxiliary marker gene.

PMID- 17004653
TI  - Fluorescence spectroscopy: a tool to characterize humic substances in soil
      colonized by microorganisms?
AB  - The ability of eight soil microfungal species, Alternaria alternata, Clonostachys
      rosea f. rosea, Exophiala cf. salmonis, Fusarium cf. coeruleum, Fusarium
      redolens, Paecilomyces lilacinus, Penicillium canescens and Phoma sp., and two
      known basidiomycete humic acid (HA) degraders, Trametes versicolor and
      Phanerochaete chrysosporium, to modify fluorescence properties of fulvic acids
      (FA) and/or HAs was determined. Effects of minerals and/or glucose on the
      modifications were examined. FA purified on polyvinyl-polypyrrolidone (PVPP)
      chromatography column was used. Purification of FA on PVPP column removed the low
      molar-mass FA-structural components and excess of extractant (NaOH) used during
      FA preparation. Excitation spectra of FA entering the purification, purified FA
      and the removal solution indicate that organic compounds rich in carboxylic
      groups dominate in the removal solution and higher content of phenolic groups is
      a characteristic of purified FA. Many microfungal species shifted the emission
      maximum (measured at 470 and 468 nm of excitation wavelength) of FA, and also HA
      to longer wavelengths. The opposite effect (shift of the HA emission maximum to
      shorter wavelengths) of microfungi was observed for HA complemented by glucose.
      Depending on the presence of glucose in the medium, most microfungi changed also
      the shape of the emission spectra of HA and FA and the excitation spectra of FA.
      HA excitation spectrum measured at 590 nm of emission wavelength was
      significantly affected by the presence of glucose. Mineral ions caused a minor
      shift in the position of excitation maximum (measured at 590 nm of emission
      wavelength) toward longer wavelengths.

PMID- 17004654
TI  - Detection of SEN virus in the general population and different risk groups in
      Slovakia.
AB  - Sera of 426 adult persons were examined to assess the prevalence of SEN virus
      (SENV) infection in Slovakia and to determine the importance of different risk
      factors for parenteral transmission. SENV prevalence was determined by the PCR
      method using primers of SENV-D and SENV-H strains. Positive results were found in
      10 of 37 patients with acute hepatitis of unknown etiology, 7 of 38 with acute
      hepatitis B, 17 of 44 with chronic hepatitis B, 29 of 102 with chronic hepatitis
      C, 36 of 72 hemodialysis patients, 2 of 33 health care workers and 24 of 100
      persons from the control group. The highest prevalence of SENV was among
      hemodialysis patients, significantly higher than in the groups of health care
      workers, acute hepatitis B and controls. The lowest prevalence was in health care
      workers group, significantly lower also in comparison with groups of chronic
      hepatitis B and C. Among the possible risk factors of virus transmission the
      average duration of hemodialysis (1.15 vs. 0.50 years), number of surgeries (1.60
      vs. 1.10) and transfusions (1.34 vs. 0.94) showed notable differences in terms of
      SENV infection. Bilirubin and aminotransferase levels did not differ between SENV
      positive and -negative groups. No pathogenetic role of SEN virus in liver injury
      was confirmed.

PMID- 17004655
TI  - Adjacent location of the bac gene and two-component regulatory system genes
      within the putative Streptococcus agalactiae pathogenicity island.
AB  - A chromosomal DNA fragment of 8992 bp in size that has not been previously
      identified in Streptococcus agalactiae, was cloned and sequenced from strain 98
      D60C. In particular, this 8992-bp fragment contained genes homologous to the
      sensor histidine kinase gene and the DNA-binding response-regulator gene of
      Streptococcus pneumoniae, and S. agalactiae bac gene. Structural and genetic
      features of the 8992-bp fragment were highly similar to those specific for
      bacterial pathogenicity islands. Analysis of epidemiologically unrelated S.
      agalactiae strains revealed that this fragment was present only in bac gene
      positive strains. The possible origin of the 8992-bp fragment in S. agalactiae
      and its significance for molecular mechanisms of "bacteria-host" interactions are
      discussed.

PMID- 17004656
TI  - Successful eradication of methicillin-resistant Staphylococcus aureus (MRSA)
      intestinal carrier status in a healthcare worker--case report.
AB  - We describe bacteriophage therapy in the case of a healthcare worker whose
      gastrointestinal tract was colonized by methicillin-resistant Staphylococcus
      aureus (MRSA) with subsequent urinary tract infection caused by the same
      pathogen. Oral treatment with anti-MRSA phages resulted in eradication of the
      carrier status.

PMID- 17004657
TI  - Oral application of Enterococcus faecium strain EE3 in healthy dogs.
AB  - The ability of canine strain Enterococcus faecium EE3 to survive in healthy dogs
      and its effect on microbiological and biochemical parameters was determined. The
      strain was individually applied to 11 dogs per os at a dose of 10(9) CFU/mL
      (differed from 2 to 3 mL) for 1 week and persisted in feces for 3 months after
      cessation of its administration (reaching average concentration of 6.83 +/- 0.95
      log CFU/g). Seven d after administration, a decrease in staphylococci and a
      significant decrease in Pseudomonas-like bacteria was observed. On the other
      hand, concentration of lactic acid bacteria increased but the growth of E. coli
      was not influenced. In the blood samples of dogs after 0-1 d (before application)
      and the blood samples 1 week after application, total lipids decreased in 8 dogs;
      the total protein also decreased. The levels of cholesterol were brought to the
      physiological level, i.e. in blood samples with low cholesterol values it
      increased to the physiological level and in those with high levels it decreased;
      cholesterol was not influenced in 3 dogs.

PMID- 17004659
TI  - Sharing your knowledge as a perioperative expert.

PMID- 17004658
TI  - Immunomodulatory effects of Bacillus firmus on mouse peritoneal cells in vitro.
AB  - The effect of nonpathogenic G+ bacterium B. firmus (BF) on stimulation of mouse
      peritoneal cells in vitro was evaluated by testing nitric-oxide-synthesis
      induction and cytokine formation. The reactivity was compared of peritoneal cells
      from two inbred mouse strains, C57B1/6 and BALB/c, which differ in their
      immunological reactivity. Peritoneal macrophages from C57B1/6 produced more
      nitric oxide after a 1-d cultivation with inactivated BF than those of BALB/c
      mice. In both strains, production can be further increased by adding exogenous
      IFN-gamma to the culture. There were no significant differences between
      peritoneal cells of these two mouse strains in cytokine production after optimal
      in vitro stimulation with BF. BF effectively activated peritoneal cells for the
      production of TNF-alpha, IL-1beta and IL-10, delipidated bacterium (DBF) being
      more efficient than BF in induction of IL-10 and TNF-alpha. On the other hand, BF
      had only small effect on IFN-gamma production and no detectable effect on IL-12
      production. Macrophage activation by BF/DBF can represent one of the mechanisms
      responsible for previously described immunomodulatory activity of BF.

PMID- 17004660
TI  - Performing in the operating theater.

PMID- 17004661
TI  - Patient discharge criteria.

PMID- 17004662
TI  - Demystifying the publishing process.

PMID- 17004663
TI  - Ergonomics in the workplace.

PMID- 17004664
TI  - Quality control in tissue banking--ensuring the safety of allograft tissues.
AB  - DESPITE FEDERAL REGULATIONS for tissue-banking practices, inadequate quality
      control led to the largest allograft tissue recall in history in October 2005.
      THE RECALL INCLUDED all allograft tissues obtained from 761 donors and
      distributed by five tissue banks. Many of these tissues already had been
      implanted and were unrecoverable. THIS ARTICLE DESCRIBES the many tissue-banking
      industry variables, including donor selection and testing and tissue recovery,
      processing, and preservation. QUESTIONS THAT HEALTH CARE providers can ask to
      determine which tissue banks' quality control measures best ensure the safety of
      the allografts they provide also are included.

PMID- 17004665
TI  - Using medical-error reporting to drive patient safety efforts.
AB  - IMPROVING PATIENT SAFETY has become one of the driving forces in health care
      delivery. Honest, accurate disclosure of medical errors and close calls is
      crucial to gain a better grasp of problems, make effective changes, and evaluate
      progress. ALTHOUGH FEAR OF MALPRACTICE litigation remains a major deterrent to
      medical-error reporting, disclosure allows organizations to benefit from one
      another's experiences. Accountability necessitates mandatory reporting to
      external organizations, but a wide variety of reporting systems exist, each with
      its own advantages and shortcomings. National standardized reporting is a major
      objective for the patient safety movement. STAFF MEMBER INVESTMENT is a key
      factor in the safety process and needs to extend beyond the reporting procedure.

PMID- 17004666
TI  - Effects of comfort warming on preoperative patients.
AB  - THERMAL COMFORT IS ONE DIMENSION of overall patient comfort, and it usually is
      addressed by covering the patient with warmed cotton blankets. WARMING HELPS A
      PATIENT maintain normothermia and appears to decrease patient anxiety. AN STUDY
      WAS CONDUCTED in a preoperative setting to compare the effects of preoperative
      warming with warmed cotton blankets versus patient-controlled warming gowns on
      patients' perceptions of thermal comfort and anxiety. BOTH WARMING INTERVENTIONS
      had a positive effect on patients' thermal comfort and sense of well-being.
      Patients who used the patient-controlled warming gown also experienced a
      significant reduction in preoperative anxiety.

PMID- 17004667
TI  - Educating nurses about correct application of cricoid pressure.
AB  - ALTHOUGH THE APPLICATION of cricoid pressure is a technique that is performed
      almost daily in the OR, perioperative nurses may not be applying cricoid pressure
      correctly. THE PURPOSE of this quality improvement project was to develop an
      education program to assess perioperative nurses' skills and educate and train
      them regarding correct application of cricoid pressure. OF 51 PERIOPERATIVE
      NURSES who participated in a pretest, an education program, and a posttest, the
      number of participants who could apply the appropriate amount of pressure to the
      correct location increased from two (3.9%) on the pretest to 35 (68.6%) on the
      posttest.

PMID- 17004668
TI  - Registered nurse peer evaluation in the perioperative setting.
AB  - ANNUAL PERFORMANCE evaluations can be difficult to prepare and may rely, in part,
      on anecdotal information. PERIOPERATIVE RNs at CHRISTUS St Patrick Hospital, Lake
      Charles, La, developed and implemented a peer evaluation as part of nurses'
      annual performance evaluations. THE EVALUATION FORMS created were considered to
      be useful and fair by both staff members and managers.

PMID- 17004669
TI  - The National Patient Safety Goals: a focus for action.

PMID- 17004670
TI  - AORN Guidance Statement: "do-not-use" abbreviations, acronyms, dosage
      designations, and symbols.

PMID- 17004671
TI  - English language learners struggling to learn to read: emergent scholarship on
      linguistic differences and learning disabilities.

PMID- 17004672
TI  - The response to intervention of English language learners at risk for reading
      problems.
AB  - The response to intervention (RTI) of English language learners identified as at
      risk for reading difficulties in the fall of first grade was examined at the end
      of first grade and at the end of second grade. Students at risk for reading
      problems were randomly assigned to intervention or control groups. Intervention
      students received supplemental reading intervention daily for 50 minutes in small
      groups from October to April. Students in the comparison condition received the
      school's existing instructional program for struggling readers. Criteria were
      established to determine adequate RTI at the end of first grade and at the end of
      second grade. The results indicated that more students who participated in the
      first-grade intervention in either Spanish or English met the established RTI
      standards than students who did not, and this finding was maintained through the
      end of second grade.

PMID- 17004673
TI  - Beyond phonology: What else is needed to describe the problems of below-average
      readers and spellers?
AB  - The difficulties experienced by below-average readers in phonological decoding
      tasks are well documented. Recent research has suggested that additional deficits
      in perceptual-motor fluency, handedness, and memory may also exist among below
      average readers. To evaluate these claims, average and below-average readers and
      spellers were compared on a range of phonological processing, verbal short-term
      and working memory, rapid naming, handedness, and perceptual-motor fluency tasks.
      Average and below-average readers were sampled in a comparable manner and were
      also comparable on age, gender, nonverbal ability, socioeconomic status, and
      ethnicity. Below-average readers and spellers performed lower than average
      readers and spellers on rhyme detection, pseudoword decoding, and rapid digit
      (but not picture) naming tasks, but showed no differences in handedness tasks or
      on a range of other perceptual-motor tasks.

PMID- 17004674
TI  - Who are the young children for whom best practices in reading are ineffective? An
      experimental and longitudinal study.
AB  - The primary purpose of this study was to identify student characteristics that
      reliably predict responsiveness and nonresponsiveness to generally effective
      early literacy interventions. Participants were 104 children, including 7 with
      special needs and Individualized Education Programs (IEPs), who were tested in
      kindergarten and first grade. Responsiveness/nonresponsiveness status was
      determined after 2 years during which children participated in best practice
      instruction (a) in kindergarten and first grade, (b) in kindergarten only, (c) in
      first grade only, or (d) in neither year. This facilitated the study of three
      groups. Always responsive students met responsiveness criteria in both years.
      Sometimes responsive students met the criteria in only one year. Nonresponsive
      students did not meet the criteria in either year. Multivariate analysis of
      variance and discriminant function analysis indicated that the three groups were
      reliably different from one another on measures of problem behavior, verbal
      memory, sentence imitation, syntactic awareness, vocabulary, naming speed, and
      segmentation. A combination of naming speed, vocabulary, sentence imitation,
      problem behavior, and amount of intervention correctly predicted 82.1% of
      nonresponsive students, 30.0% of sometimes responsive students, and 84.1% of
      always responsive students. Fifty students from kindergarten and first grade were
      tested again at the end of what should have been their third-grade year. All but
      1 of the nonresponsive students who received intervention had been identified as
      requiring special education and had an IEP with reading goals.

PMID- 17004675
TI  - Comparisons of achievement, effort, and self-perceptions among students with
      learning disabilities and their peers from different achievement groups.
AB  - This study compared the social-emotional implications of academic achievement for
      students with and without learning disabilities (LD) and identified predictors of
      effort investment. Students with LD showed lower levels of achievement, effort
      investment, academic self-efficacy, sense of coherence, positive mood, and hope,
      and higher levels of loneliness and negative mood. When compared to peers without
      LD (n = 447) at four different academic achievement levels, students with LD
      showed higher achievement than the low-average group, but their social-emotional
      profiles were similar to the low and low-average groups. Hierarchical multiple
      regression analysis showed that achievement, academic self-efficacy, negative
      mood, and hope predicted effort investment for students with LD. These results
      demonstrated the importance of hope in understanding the functioning of students
      with LD.

PMID- 17004676
TI  - An evaluation of intensive intervention for students with persistent reading
      difficulties.
AB  - To evaluate the effects of an intensive tertiary reading intervention, 27
      students with severe reading difficulties and disabilities, 14 of whom had
      demonstrated an inadequate response to 1-2 tiers of prior reading instruction,
      received a 16-week intervention package involving decoding and fluency skills.
      The decoding intervention was provided for 2 hours per day for 8 weeks and was
      based on the Phono-Graphix program. The fluency intervention followed the
      decoding intervention and involved 1 hour of daily instruction for 8 weeks based
      on the Read Naturally program. The 16-week intervention resulted in significant
      improvement in reading decoding, fluency, and comprehension. Although individual
      responses to the intervention were variable, 12 of the 27 students showed a
      significant response to these interventions. Students who had participated in
      previous Tier 1 plus Tier 2 interventions but remained impaired had a stronger
      response to intervention in the current study than students who had previously
      participated only in Tier 1 intervention and students who had not received prior
      intervention outside of special education.

PMID- 17004677
TI  - The effects of computer-assisted instruction on number combination skill in at
      risk first graders.
AB  - The purpose of this pilot study was to assess the potential for computer-assisted
      instruction (CAI) to enhance number combination skill among children with
      concurrent risk for math disability and reading disability. A secondary purpose
      was to examine the effects of CAI on spelling. At-risk students were assigned
      randomly to math or spelling CAI, which they received in 50 sessions over 18
      weeks. Acquisition and transfer effects were assessed. The results indicated that
      math CAI was effective in promoting addition but not subtraction number
      combination skill and that transfer to arithmetic story problems did not occur.
      Spelling CAI effects were reliable on acquisition and transfer spelling measures,
      with small to moderate effect sizes on transfer to reading measures. These
      results provide the basis for additional work with larger samples.

PMID- 17004678
TI  - Feasibility of soil dust source apportionment by the pyrolysis-gas
      chromatography/mass spectrometry method.
AB  - This study tested the feasibility of using pyrolysis (Py)-gas chromatography
      (GC)/mass spectrometry (MS) to obtain organic chemical species data suitable for
      source apportionment modeling of soil-derived coarse particulate matter (PM10)
      dust on ambient filters. A laboratory resuspension apparatus was used with known
      soils to generate simulated receptor filter samples loaded with approximately 0.4
      mg of PM10 dust, which is within the range of mass loading on ambient filters. Py
      GC/MS at 740 degrees C generated five times more resolvable compounds than were
      obtained with thermal desorption GC/MS at 315 degrees C. The identified compounds
      were consistent with literature from Py experiments using larger samples of bulk
      soils. A subset of 91 organic species out of the 178 identified Py products was
      used as input to CMB8 software in a demonstration of source apportionment using
      laboratory-generated mixtures simulating ambient filter samples. The 178
      quantified organic species obtained by Py of soil samples is an improvement
      compared with the 38 organic species obtained by thermal desorption of soils and
      the four functionally defined organic fractions reported by thermal/ optical
      reflectance. Significant differences in the concentration of specific species
      were seen between samples from different sites, both geographically distant and
      close, using analysis of variance and cluster analysis. This feasibility study
      showed that Py-GC/MS can generate useful source profile data for receptor
      modeling and justifies continued method development.

PMID- 17004679
TI  - Characteristics of inhalable particulate matter concentration and size
      distribution from power plants in China.
AB  - In this investigation, the collection efficiency of particulate emission control
      devices (PECDs), particulate matter (PM) emissions, and PM size distribution were
      determined experimentally at the inlet and outlet of PECDs at five coal-fired
      power plants. Different boilers, coals, and PECDs are used in these power plants.
      Measurement in situ was performed by an electrical low-pressure impactor with a
      sampling system, which consisted of an isokinetic sampler probe, precut cyclone,
      and two-stage dilution system with a sample line to the instruments. The size
      distribution was measured over a range from 0.03 to 10 microm. Before and after
      all of the PECDs, the particle number size distributions display a bimodal
      distribution. The PM2.5 fraction emitted to atmosphere includes a significant
      amount of the mass from the coarse particle mode. The controlled and uncontrolled
      emission factors of total PM, inhalable PM (PM10), and fine PM P(M2.5) were
      obtained. Electrostatic precipitator (ESP) and baghouse total collection
      efficiencies are 96.38-99.89% and 99.94%, respectively. The minimum collection
      efficiency of the ESP and the baghouse both appear in the particle size range of
      0.1-1 microm. In this size range, ESP and baghouse collection efficiencies are
      85.79-98.6% and 99.54%. Real-time measurement shows that the mass and number
      concentration of PM10 will be greatly affected by the operating conditions of the
      PECDs. The number of emitted particles increases with increasing boiler load
      level because of higher combustion temperature. During test run periods, the data
      reproducibility is satisfactory.

PMID- 17004680
TI  - Model estimation and measurement of ammonia emission from naturally ventilated
      dairy cattle buildings with slatted floor designs.
AB  - Laboratory experiments were carried out in a wind tunnel with a model of a slurry
      pit to investigate the characteristics of ammonia emission from dairy cattle
      buildings with slatted floor designs. Ammonia emission at different temperatures
      and air velocities over the floor surface above the slurry pit was measured with
      uniform feces spreading and urine sprinkling on the surface daily. The data were
      used to improve a model for estimation of ammonia emission from dairy cattle
      buildings. Estimates from the updated emission model were compared with measured
      data from five naturally ventilated dairy cattle buildings. The overall measured
      ammonia emission rates were in the range of 11-88 g per cow per day at air
      temperatures of 2.3-22.4 degrees C. Ammonia emission rates estimated by the model
      were in the range of 19-107 g per cow per day for the surveyed buildings. The
      average ammonia emission estimated by the model was 11% higher than the mean
      measured value. The results show that predicted emission patterns generally agree
      with the measured one, but the prediction has less variation. The model
      performance may be improved if the influence of animal activity and management
      strategy on ammonia emission could be estimated and more reliable data of air
      velocities of the buildings could be obtained.

PMID- 17004681
TI  - Validation of the digital opacity compliance system under regulatory enforcement
      conditions.
AB  - U.S. Environmental Protection Agency (EPA) Emission Measurement Center in
      conjunction with EPA Regions VI and VIII, the state of Utah, and the U.S.
      Department of Defense have conducted a series of long-term pilot and field tests
      to determine the accuracy and reliability of a visible opacity monitoring system
      consisting of a conventional digital camera and a separate computer software
      application for plume opacity determination. This technology, known as the
      Digital Opacity Compliance System (DOCS), has been successfully demonstrated at
      EPA-sponsored Method-9 "smoke schools", as well as at a number of government and
      commercially operated industrial facilities. Results from the current DOCS
      regulatory pilot study demonstrated that, under regulatory enforcement
      conditions, the average difference in opacity measurement between the DOCS
      technology and EPA Reference Method 9 (Method 9) was 1.12%. This opacity
      difference, which was computed from the evaluation of 241 regulated air sources,
      was found to be statistically significant at the 99% confidence level. In
      evaluating only those sources for which a nonzero visible opacity level was
      recorded, the

PMID- 17004682
TI  - Wintertime vertical variations in particulate matter (PM) and precursor
      concentrations in the San Joaquin Valley during the California Regional Coarse
      PM/Fine PM Air Quality Study.
AB  - Air quality monitoring was conducted at a rural site with a tower in the middle
      of California's San Joaquin Valley (SJV) and at elevated sites in the foothills
      and mountains surrounding the SJV for the California Regional PM10/ PM2.5 Air
      Quality Study. Measurements at the surface and n a tower at 90 m were collected
      in Angiola, CA, from December 2000 through February 2001 and included hourly
      black carbon (BC), particle counts from optical particle counters, nitric oxide,
      ozone, temperature, relative humidity, wind speed, and direction. Boundary site
      measurements were made primarily using 24-hr integrated particulate matter (PM)
      samples. These measurements were used to understand the vertical variations of PM
      and PM precursors, the effect of stratification in the winter on concentrations
      and chemistry aloft and at the surface, and the impact of aloft-versus-surface
      transport on PM concentrations. Vertical variations of concentrations differed
      among individual species. The stratification may be important to atmospheric
      chemistry processes, particularly nighttime nitrate formation aloft, because NO2
      appeared to be oxidized by ozone in the stratified aloft layer. Additionally,
      increases in accumulation-mode particle concentrations in the aloft layer during
      a fine PM (PM2.5) episode corresponded with increases in aloft nitrate,
      demonstrating the likelihood of an aloft nighttime nitrate formation mechanism.
      Evidence of local transport at the surface and regional transport aloft was
      found; transport processes also varied among the species. The distribution of BC
      appeared to be regional, and BC was often uniformly mixed vertically. Overall,
      the combination of time-resolved tower and surface measurements provided
      important insight into PM stratification, formation, and transport.

PMID- 17004683
TI  - Investigation of the ultraviolet photolysis method for the determination of
      organic nitrogen in aerosol samples.
AB  - The research objective was to adapt the ultraviolet (UV)-photolysis method to
      determine dissolved organic nitrogen (DON) in aqueous extracts of aerosol
      samples. DON was assumed to be the difference in total concentration of inorganic
      nitrogen forms before and after sample irradiation. Using a 2(2) factorial design
      the authors found that the optimal conversion of urea, amino acids (alanine,
      aspartic acid, glycine, and serine), and methylamine for a reactor temperature of
      44 degrees C occurred at pH 2.0 with a 24-hr irradiance period at concentrations
      <33 microM of organic nitrogen. Different decomposition mechanisms were evident:
      the photolysis of amino acids and methylamine released mainly ammonium (NH4+),
      but urea released a near equimolar ratio of NH4+ and nitrate (NO3-). The method
      was applied to measure DON in the extracts of aerosol samples from Tampa, FL,
      over a 32-day sampling period. Average dissolved inorganic (DIN) and DON
      concentrations in the particulate matter fraction PM10 were 78.1 +/- 29.2 nmol
      Nm(-3) and 8.3 +/- 4.9 nmol-Nm(-3), respectively. The ratio between DON and total
      dissolved nitrogen ([TDN] = DIN + DON) was 10.1 +/- 5.7%, and the majority of the
      DON (79.1 +/- 18.2%) was found in the fine particulate matter (PM2.5) fraction.
      The average concentrations of DIN and DON in the PM2.5 fraction were 54.4 +/-
      25.6 nmol-Nm(-3) and 6.5 +/- 4.4 nmol-Nm(-3), respectively.

PMID- 17004685
TI  - Apportionment of ambient primary and secondary pollutants during a 2001 summer
      study in Pittsburgh using U.S. Environmental Protection Agency UNMIX.
AB  - Apportionment of primary and secondary pollutants during the summer 2001
      Pittsburgh Air Quality Study (PAQS) is reported. Several sites were included in
      PAQS, with the main site (the supersite) adjacent to the Carnegie Mellon
      University campus in Schenley Park. One of the additional sampling sites was
      located at the National Energy Technology Laboratory, located approximately 18 km
      southeast of downtown Pittsburgh. Fine particulate matter (PM2.5) mass, gas-phase
      volatile organic material (VOM), particulate semivolatile and nonvolatile organic
      material (NVOM), and ammonium sulfate were apportioned at the two sites into
      their primary and secondary contributions using the U.S. Environmental Protection
      Agency UNMIX 2.3 multivariate receptor modeling and analysis software. A portion
      of each of these species was identified as originating from gasoline and diesel
      primary mobile sources. Some of the organic material was formed from local
      secondary transformation processes, whereas the great majority of the secondary
      sulfate was associated with regional transformation contributions. The results
      indicated that the diurnal patterns of secondary gas-phase VOM and particulate
      semivolatile and NVOM were not correlated with secondary ammonium sulfate
      contributions but were associated with separate formation pathways. These
      findings are consistent with the bulk of the secondary ammonium sulfate in the
      Pittsburgh area being the result of contributions from distant transport and,
      thus, decoupled from local activity involving organic pollutants in the
      metropolitan area.

PMID- 17004684
TI  - Comparison of source apportionments of fine particulate matter at two San Jose
      speciation trends network sites.
AB  - In this study, the chemical composition of fine particulate matter samples
      collected at U.S. Environmental Protection Agency Speciation Trends Network sites
      in San Jose, CA, from February 2000 to February 2005 were analyzed. A San Jose
      site was initially established at 4th Street and then subsequently moved to
      Jackson Street in mid-2002. These sites are approximately 1 km apart. There were
      no known major changes in the nature of the sources in the area over this period.
      The study used positive matrix factorization model to extract the source profiles
      and their mass contributions and to compare the results for the congruence of the
      source apportionments between these two nearby sites. In the case of the 4th
      Street site, the average mass was apportioned to wood combustion (32.1 +/- 2.5%),
      secondary nitrate (22.3 +/- 2%), secondary sulfate (10.7 +/- 0.6%), fresh sea
      salt (7.7 +/- 0.9%), gasoline vehicles (7.3 +/- 0.5%), aged sea salt (6.8 +/-
      0.4%), road dust (6.7 +/- 0.7%), diesel emissions (3.9 +/- 0.3%), and a Ni
      related industrial source (2.5 +/- 0.4%). At the Jackson Street site, the average
      mass was apportioned to wood combustion (33.6 +/- 2.6%), secondary nitrate (20.3
      +/- 1.9%), secondary sulfate (13.9 +/- 0.9%), aged sea salt (12.4 +/- 0.7%),
      gasoline vehicle (8.3 +/- 0.6%), fresh sea salt (5.3 +/- 0.5%), diesel emission
      (3.2 +/- 0.3%), road dust (1.9 +/- 0.1%), and Ni-related industrial source (1.3
      +/- 0.1%). Conditional probability function analysis was used to help identify
      local sources. These results suggested that moving the sampling site a short
      distance had little effect on the nature of the resolved source types although
      some differences in their quantitative impacts were obtained in the positive
      matrix factorization analyses.

PMID- 17004686
TI  - Designing a low-cost pollution prevention plan to pay off at the University of
      Houston.
AB  - The University of Houston is located just south of downtown Houston, TX. Many
      different chemical substances are used in scientific research and teaching
      activities throughout the campus. These activities generate a significant amount
      of waste materials that must be discarded as regulated hazardous waste per U.S.
      Environmental Protection Agency (EPA) rules. The Texas Commission on
      Environmental Quality (TCEQ) is the state regulatory agency that has enforcement
      authority for EPA hazardous waste rules in Texas. Currently, the University is
      classified as a large quantity generator and generates >1000 kg per month of
      hazardous waste. In addition, the University has experienced a major surge in
      research activities during the past several years, and overall the quantity of
      the hazardous waste generated has increased. The TCEQ requires large quantity
      generators to prepare a 5-yr Pollution Prevention (P2) Plan, which describes
      efforts to eliminate or minimize the amount of hazardous waste generated. This
      paper addresses the design and development of a low-cost P2 plan with minimal
      implementation obstacles and strong payoff potentials for the University. The
      projects identified can be implemented with existing University staff resources.
      This benefits the University by enhancing its environmental compliance efforts,
      and the disposal cost savings can be used for other purposes. Other educational
      institutions may benefit by undertaking a similar process.

PMID- 17004687
TI  - The Southeastern Aerosol Research and Characterization Study, part 3: continuous
      measurements of fine particulate matter mass and composition.
AB  - Deployment of continuous analyzers in the Southeastern Aerosol Research and
      Characterization Study (SEARCH) network began in 1998 and continues today as new
      technologies are developed. Measurement of fine particulate matter (PM2.5) mass
      is performed using a dried, 30 degrees C tapered element oscillating microbalance
      (TEOM). TEOM measurements are complemented by observations of light scattering by
      nephelometry. Measurements of major constituents include: (1) SO4(2-) via
      reduction to SO2; (2) NH4+ and NO3- via respective catalytic oxidation and
      reduction to NO, (3) black carbon (BC) by optical absorption, (4) total carbon by
      combustion to CO2, and (5) organic carbon by difference between the latter two
      measurements. Several illustrative examples of continuous data from the SEARCH
      network are presented. A distinctive composite annual average diurnal pattern is
      observed for PM2.5 mass, nitrate, and BC, likely indicating the influence of
      traffic-related emissions, growth, and break up of the boundary layer and
      formation of ammonium nitrate. Examination of PM2.5 components indicates the need
      to better understand the continuous composition of the unmeasured "other"
      category, because it contributes a significant fraction to total mass during
      periods of high PM2.5 loading. Selected episodes are presented to illustrate
      applications of SEARCH data. An SO2 conversion rate of 0.2%/hr is derived from an
      observation of a plume from a coal-fired power plant during early spring, and the
      importance of local, rural sources of NH3 to the formation of ammonium nitrate in
      particulate matter (PM) is demonstrated.

PMID- 17004688
TI  - Determination and impact of volatile organics emitted during rush hours in the
      ambient air around gasoline stations.
AB  - This study analyzes the volatile organic compounds (VOCs) in the ambient air
      around gasoline stations during rush hours and assesses their impact on human
      health. Results from this study clearly indicate that methyl tertiary butyl ether
      (MTBE), toluene, and isobutane are the major VOCs emitted from gasoline stations.
      Moreover, the concentrations of MTBE and toluene in the ambient air near gasoline
      stations are remarkably higher than those sampled on surrounding roads, revealing
      that these compounds are mainly released from gasoline stations. The
      concentration of VOCs near the gasoline stations without vapor recovery systems
      are approximately 7.3 times higher than those around the gasoline stations having
      the recovery systems. An impact on individual health and air quality because of
      gasoline station emissions was done using Integrated Risk Information System and
      Industrial Source Complex Short Term model.

PMID- 17004689
TI  - Modernisation is key to survival of district nursing.

PMID- 17004691
TI  - Question time.
AB  - Choosing to train as a nurse is a major decision, rife with different emotions
      and considerations. Regardless of what point you have reached in your studies,
      whether you are studying towards a degree or diploma, whatever your age and
      whether you are from the UK or overseas, you face common challenges. These
      include surviving financially, juggling study and clinical placements, learning
      new information and addressing patients' needs. While the profession certainly
      offers exciting opportunities, nursing students in 2006 face a range of
      uncertainties. There have been cuts and freezes to existing and vacant posts
      across NHS trusts, while students from overseas face the additional problem that
      band 5 and 6 nursing posts have been removed from the Home Office's shortage
      occupation list. Will there be enough mentors to teach students? Will there be
      jobs when they qualify? How can students survive financially? Will overseas
      students be able to stay once qualified? NT put students' key questions to a
      panel of experts and influential figures.

PMID- 17004692
TI  - Student survival guide.

PMID- 17004693
TI  - Ten ways to study success.

PMID- 17004694
TI  - Role of graduate mental health workers within primary care.
AB  - The concept of primary healthcare graduate mental health workers came into being
      following the implementation of The NHS Plan (Department of Health, 2000) and the
      National Service Framework for Mental Health (DH, 1999). It is now generally
      agreed that service users must be consulted in order to fully understand and
      judge the effectiveness of this new role. It is this knowledge that can then
      position precisely where this new role will fit within the NHS's mental health
      organisational structure.

PMID- 17004695
TI  - Mouth-to-mouth ventilation.

PMID- 17004696
TI  - Offering assistance at road traffic incidents while off duty.
AB  - Every year in the UK road traffic incidents cause 320,000 injuries--40,000 of
      which are serious--and over 3,200 deaths. The public, patients and relatives
      expect nurses to be able to assist and provide first aid at the scene of any
      emergency. As a healthcare professional you should therefore ensure you are up to
      date with first aid skills.

PMID- 17004697
TI  - Using the Liverpool Care Pathway in a nursing home.
AB  - The Liverpool Care Pathway provides evidence-based guidelines relating to the
      care of dying patients. This article outlines a pilot project to introduce it to
      a 150-bed BUPA nursing home.

PMID- 17004698
TI  - Identifying the development needs of community matrons.
AB  - AIM: To gain some insight into the needs of community matrons from both the
      practitioners' and managers' perspectives. METHOD: Focus groups with community
      matrons in different PCTs. RESULTS: The focus groups identified that skills in
      physical assessment and prescribing were taken as prerequisites or essential to
      the role, and that the educational priorities were viewed as clinical education
      relating to the management of many long-term conditions linked to major causes of
      unplanned admissions. The preferred format for education appears to be work-based
      learning delivered by clinicians. CONCLUSION: PCTs need to ensure that community
      matrons have their learning needs assessed and to put in place systems of work
      based learning that allow for appropriate development. Although community matrons
      themselves may not initially see the value of non-clinical education, this will
      be vital to the long-term success of their role.

PMID- 17004699
TI  - A patient group with complex needs.

PMID- 17004700
TI  - Prediction of protein-ligand interactions. Docking and scoring: successes and
      gaps.

PMID- 17004701
TI  - Parameter estimation for scoring protein-ligand interactions using negative
      training data.
AB  - Surflex-Dock employs an empirically derived scoring function to rank putative
      protein-ligand interactions by flexible docking of small molecules to proteins of
      known structure. The scoring function employed by Surflex was developed purely on
      the basis of positive data, comprising noncovalent protein-ligand complexes with
      known binding affinities. Consequently, scoring function terms for improper
      interactions received little weight in parameter estimation, and an ad hoc scheme
      for avoiding protein-ligand interpenetration was adopted. We present a
      generalized method for incorporating synthetically generated negative training
      data, which allows for rigorous estimation of all scoring function parameters.
      Geometric docking accuracy remained excellent under the new parametrization. In
      addition, a test of screening utility covering a diverse set of 29 proteins and
      corresponding ligand sets showed improved performance. Maximal enrichment of true
      ligands over nonligands exceeded 20-fold in over 80% of cases, with enrichment of
      greater than 100-fold in over 50% of cases.

PMID- 17004702
TI  - Molecular complexity analysis of de novo designed ligands.
AB  - The de novo approach to structure-based rational drug design can provide a
      powerful tool for suggestion of entirely novel potential leads. However, programs
      for structure generation typically generate large numbers of putative ligands;
      therefore, various heuristics (such as estimation of binding affinity and
      synthetic accessibility) have to be adopted to evaluate and prune large answer
      sets with the goal of suggesting ligands with high binding affinity but low
      structural complexity. A novel method for complexity analysis is described. This
      method provides a rapid and effective ranking technique for elimination of
      structures with complicated molecular motifs. This complexity analysis technique,
      implemented within the SPROUT de novo design system, is based on the statistical
      distribution of various cyclic and acyclic topologies and atom substitution
      patterns in existing drugs or commercially available starting materials. A novel
      feature of the technique that distinguishes it from other published methods is
      that the matching takes place at various levels of abstraction, so that it can
      evaluate complexity scores, even for structures which contain atoms with
      unspecified atom type, which is sometimes the case with the initial output of de
      novo structure generation systems.

PMID- 17004703
TI  - Contribution of conformer focusing to the uncertainty in predicting free energies
      for protein-ligand binding.
AB  - When a ligand binds to a protein, it is typically not in the lowest-energy
      conformation for the unbound ligand and there is also a loss of conformational
      degrees of freedom. The free-energy change for this "conformer focusing" is
      addressed here formally, and the associated errors with its estimation or neglect
      are considered in the context of scoring functions for protein-ligand docking and
      computation of absolute free energies of binding. Specific applications for
      inhibition of HIV-1 reverse transcriptase are reported. It is concluded that the
      uncertainties from this source alone are sufficient to preclude the viability of
      current docking methodology for rank-ordering of diverse compounds in high
      throughput virtual screening.

PMID- 17004704
TI  - A method for induced-fit docking, scoring, and ranking of flexible ligands.
      Application to peptidic and pseudopeptidic beta-secretase (BACE 1) inhibitors.
AB  - Inhibition of beta-secretase (BACE 1) has recently been investigated as a
      promising therapeutic approach in the treatment of Alzheimer's disease, and a
      growing number of BACE 1 inhibitors and crystal structures of BACE 1/inhibitors
      complexes have been reported. We report herein a predictive computational method
      and its application to potential BACE 1 inhibitors. Using a training set of 50
      known highly flexible inhibitors, we developed a docking method that accounts for
      the flexibility of both the protein and the inhibitors. Protein flexibility is
      accounted for using a specifically designed genetic algorithm. We next developed
      a scoring function consisting of force field evaluation of the inhibitor/protein
      interactions and two additional terms for hydrogen bonding and entropy change
      upon binding. Discarding three outliers from the training set, our protocol was
      found to perform well with an rmsd of 1.19 kcal/mol. Evaluation of the predictive
      power was next carried out by virtual screening of 80 synthetic compounds. The
      significant enrichment at the top of the ranking list in active compounds
      demonstrated the ability of the docking and scoring protocol to rank the
      compounds relative to their activities.

PMID- 17004705
TI  - PMF scoring revisited.
AB  - Knowledge-based scoring functions have become accepted choices for fast scoring
      putative protein-ligand complexes according to their binding affinities. Since
      their introduction 5 years ago, the knowledge base of protein-ligand complexes
      has grown to the point were rederiving potentials of mean force becomes
      meaningful for statistical reasons. Revisiting potential of mean force (PMF)
      scoring (J. Med. Chem. 1999, 42, 791), we present an updated PMF04 scoring
      function that is based on 7152 protein-ligand complexes from the PDB. This
      constitutes an increase of about 10-fold compared to the knowledge base of the
      original PMF99 score (697 complexes). Because of the increased statistical basis
      of the PMF04 score, potentials for metal ions have been derived for the first
      time. In addition, potentials for halogens have reached statistical significance
      and are included also. Comparison of scoring accuracies between PMF99 and PMF04
      shows an increased performance of the new score for many well-established test
      sets. Extending the testing of PMF scoring to the recently introduced PDBbind
      database containing the large number of 800 protein-ligand complexes illustrates
      the current limits of the approach.

PMID- 17004706
TI  - M-score: a knowledge-based potential scoring function accounting for protein atom
      mobility.
AB  - A knowledge-based potential scoring function, named M-Score, has been developed
      based upon 2331 high-resolution crystal structures of protein-ligand complexes. M
      Score considers the mobility of protein atoms, describing the location of each
      protein atom by a Gaussian distribution instead of a fixed position based upon
      the isotropic B-factors. This leads to an increase in the number of atom-pairs in
      the construction of knowledge-based potentials and a smoothing effect on the
      pairwise distribution functions. M-Score was validated using 896 complexes which
      were not included in the 2331 data set and whose experimentally determined
      binding affinities were available. The overall linear correlation coefficient (r)
      between the calculated scores and experimentally determined binding affinities
      (pKi or pKd) for these 896 complexes is -0.49. Evaluation of M-Score against 17
      protein families showed that we obtained good to excellent correlations for six
      protein families, modest correlations for four protein families, and poor
      correlations for the remaining seven protein families.

PMID- 17004707
TI  - A critical assessment of docking programs and scoring functions.
AB  - Docking is a computational technique that samples conformations of small
      molecules in protein binding sites; scoring functions are used to assess which of
      these conformations best complements the protein binding site. An evaluation of
      10 docking programs and 37 scoring functions was conducted against eight proteins
      of seven protein types for three tasks: binding mode prediction, virtual
      screening for lead identification, and rank-ordering by affinity for lead
      optimization. All of the docking programs were able to generate ligand
      conformations similar to crystallographically determined protein/ligand complex
      structures for at least one of the targets. However, scoring functions were less
      successful at distinguishing the crystallographic conformation from the set of
      docked poses. Docking programs identified active compounds from a
      pharmaceutically relevant pool of decoy compounds; however, no single program
      performed well for all of the targets. For prediction of compound affinity, none
      of the docking programs or scoring functions made a useful prediction of ligand
      binding affinity.

PMID- 17004708
TI  - N-phosphonacetyl-L-isoasparagine a potent and specific inhibitor of Escherichia
      coli aspartate transcarbamoylase.
AB  - The synthesis of a new inhibitor, N-phosphonacetyl-L-isoasparagine (PALI), of
      Escherichia coli aspartate transcarbamoylase (ATCase) is reported, as well as
      structural studies of the enzyme.PALI complex. PALI was synthesized in 7 steps
      from beta-benzyl L-aspartate. The KD of PALI was 2 microM. Kinetics and small
      angle X-ray scattering experiments showed that PALI can induce the cooperative
      transition of ATCase from the T to the R state. The X-ray structure of the
      enzyme.PALI complex showed 22 hydrogen-bonding interactions between the enzyme
      and PALI. The kinetic characterization and crystal structure of the ATCase.PALI
      complex also provides detailed information regarding the importance of the alpha
      carboxylate for the binding of the substrate aspartate.

PMID- 17004710
TI  - Design, synthesis, and biological evaluation of new 1,8-naphthyridin-4(1H)-on-3
      carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives as CB2 selective
      agonists.
AB  - On the basis of docking studies carried out using the recently published
      cannabinoid receptor models,35 new 1,8-naphthyridin-4(1H)-on-3-carboxamide and
      quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and
      tested for their affinities toward the cannabinoid CB1 and CB2 receptors.
      Compound 10, which presented p-fluorobenzyl and carboxycycloheptylamide
      substituents bound in the 1 and 3 positions of the 1,8-naphthyiridine-4-one
      nucleus, showed a high CB2 affinity with a Ki of 1.0 nM. The substitution of the
      naphthyridine-4-one nucleus with the quinoline-4-one system determined a general
      increase in CB2 affinity. In particular, the N-cyclohexyl-7-chloro-1-(2-morpholin
      4-ylethyl)quinolin-4(1H)-on-3-carboxamide (40) possessed a remarkable affinity,
      with Ki of 3.3 nM, which was also accompanied by a high selectivity for the CB2
      receptor (Ki(CB1)/Ki(CB2) ratio greater than 303). Moreover, the [35S]GTPgamma
      binding assay and functional studies on human basophils indicated that the 1,8
      naphthyridin-4(1H)-on-3-carboxamide derivatives behaved as CB1 and CB2 receptor
      agonists.

PMID- 17004709
TI  - Using fragment cocktail crystallography to assist inhibitor design of Trypanosoma
      brucei nucleoside 2-deoxyribosyltransferase.
AB  - The 1.8 A resolution de novo structure of nucleoside 2-deoxyribosyltransferase
      (EC 2.4.2.6) from Trypanosoma brucei (TbNDRT) has been determined by SADa phasing
      in an unliganded state and several ligand-bound states. This enzyme is important
      in the salvage pathway of nucleoside recycling. To identify novel lead compounds,
      we exploited "fragment cocktail soaks". Out of 304 compounds tried in 31
      cocktails, four compounds could be identified crystallographically in the active
      site. In addition, we demonstrated that very short soaks of approximately 10 s
      are sufficient even for rather hydrophobic ligands to bind in the active site
      groove, which is promising for the application of similar soaking experiments to
      less robust crystals of other proteins.

PMID- 17004711
TI  - Antibacterial agent discovery using thymidylate synthase biolibrary screening.
AB  - Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2'
      deoxyuridine 5'-monophosphate to 2'-deoxythymidine 5'-monophosphate, an essential
      precursor for DNA synthesis. A specific inhibition of this enzyme induces
      bacterial cell death. As a second round lead optimization design, new 1,2
      naphthalein derivatives have been synthesized and tested against a TS-based
      biolibrary, including human thymidylate synthase (hTS). Docking studies have been
      performed to rationalize the experimentally observed affinity profiles of 1,2
      naphthalein compounds toward Lactobacillus casei TS and hTS. The best TS
      inhibitors have been tested against a number of clinical isolates of Gram
      positive-resistant bacterial strains. Compound 3,3-bis(3,5-dibromo-4
      hydroxyphenyl)-1H,3H-naphtho[1,2-c]furan-1-one (5) showed significant
      antibacterial activity, no in vitro toxicity, and dose-response effects against
      Staphylococcus epidermidis (MIC=0.5-2.5 microg/mL) clinical isolate strains,
      which are resistant to at least 17 of the best known antibacterial agents,
      including vancomycin. So far this compound can be regarded as a leading
      antibacterial agent.

PMID- 17004712
TI  - Biarylpyrazole inverse agonists at the cannabinoid CB1 receptor: importance of
      the C-3 carboxamide oxygen/lysine3.28(192) interaction.
AB  - The biarylpyrazole, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)
      4-methyl-1H-pyrazole-3-carboxamide (SR141716; 1) has been shown to act as an
      inverse agonist/antagonist at the cannabinoid CB1 receptor. Our previous mutant
      cycle study suggested that K3.28(192) is involved in a direct interaction with
      the C-3 substituent of 1 in wild-type (WT) CB1.(1) However, these results did not
      establish what part of the C-3 substituent of 1 is involved in the K3.28(192)
      hydrogen bond, the carboxamide oxygen or the piperidine nitrogen. Furthermore,
      our previous calcium channel assay results for 5-(4- chlorophenyl)-3-[(E)-2
      cyclohexylethenyl]-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole (VCHSR; 2) (an
      analogue of 1 that lacks hydrogen-bonding capability in its C-3 substituent)
      showed that this compound acts as a neutral antagonist, a result that is in
      contrast to 1, which acts as an inverse agonist in this same assay.(1) These
      results suggested a relationship between biarylpyrazole interaction with
      K3.28(192) at CB1 and inverse agonism, but these results were for a single pair
      of compounds (1 and 2). The work presented here was designed to test two
      hypotheses derived from our modeling and mutant cycle results. The hypotheses are
      as follows: (1) it is the carboxamide oxygen of the C-3 substituent of 1 that
      interacts directly with K3.28(192) and (2) the interaction with K3.28(192) is
      crucial for the production of inverse agonism for biarylpyrazoles such as 1. To
      determine whether the carboxamide oxygen or the piperidine nitrogen of the C-3
      substituent may be the interaction site for K3.28(192), we designed, synthesized,
      and evaluated a new set of analogues of 1 (3-6, Chart 1) in which modifications
      only to the C-3 substituent of 1 have been made. In each case, the modifications
      that were made preserved the geometry of this substituent in 1. The absence of
      the piperidine nitrogen was not found to affect affinity, whereas the absence of
      the carboxamide oxygen resulted in a reduction in affinity. CB1 docking studies
      in an inactive state model of CB1 resulted in the trend, 3,1<5,4<2<6 for
      ligand/CB1 interaction energies. This trend was consistent with the trend in WT
      CB1 Ki values versus [3H]CP55,940 reported here. In calcium channel assays, all
      analogues with carboxamide oxygens (1, 3, and 4) were found to be inverse
      agonists, whereas those that lacked this group (2, 5, and 6) were found to be
      neutral antagonists. Taken together, these results support the hypothesis that it
      is the carboxamide oxygen of the C-3 substituent of 1 that engages in a hydrogen
      bond with K3.28(192) in WT CB1. Furthermore, functional results for 1-6 support
      the hypothesis that the interaction of 1 with K3.28(192) may be key to its
      inverse agonism.

PMID- 17004713
TI  - A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors.
AB  - An early step of the inflammatory response, the rolling of leukocytes on
      activated endothelial cells, is mediated by selectin/carbohydrate interactions.
      The tetrasaccharide sialy Lewisx is a ligand for E-, P-, and L-selectin and
      therefore serves as a lead structure for the development of analogues. A
      combination of synthesis and structure-based design allowed rapid optimization.
      The current lead 2a was evaluated in our E-selectin cell flow chamber assay where
      it proved to inhibit rolling and adhesion with an IC50 of 28+/-7 microM. The
      assays used are predictive for the in vivo efficacy of test compounds as shown
      for 2a in a proteose peptone induced peritonitis model of acute inflammation in
      mice.

PMID- 17004714
TI  - Synthesis and immunobiological activity of an original series of acyclic lipid a
      mimics based on a pseudodipeptide backbone.
AB  - Ndelta-L-Homoserinyl-D-ornithinol pseudodipeptides N-acylated with typical
      Escherichia coli lipid A fatty acid residues and mono-O- or bis-O-phosphorylated
      have been prepared and their properties investigated. The derivatives carrying
      two phosphate groups were found to be inducers of NO production. In addition,
      while they were unable to induce significantly the production of interleukin-6
      (IL-6) by human PBMC cells, these compounds behaved also as potent antagonists of
      LPS-induced IL-6 production in the same human cells system. In conclusion, the
      molecules described here are the first members of an original class of
      immunobiologically active lipid A mimics based on an acyclic pseudodipeptide
      backbone carrying only the essential functionalities of the parent lipid A
      structure (OM-174). As the products exhibit very low endotoxicity and
      pyrogenicity, this class of lipid A mimics therefore opens a new generation of
      immunoadjuvants that possibly could reach clinical applications.

PMID- 17004716
TI  - Pyrazolidine-3,5-diones and 5-hydroxy-1H-pyrazol-3(2H)-ones, inhibitors of UDP-N
      acetylenolpyruvyl glucosamine reductase.
AB  - A series of pyrazolidine-3,5-dione and 5-hydroxy-1H-pyrazol-3(2H)-one inhibitors
      of Escherichia coli UDP-N-acetylenolpyruvyl glucosamine reductase (MurB) has been
      prepared. The 5-hydroxy-1H-pyrazol-3(2H)-ones show low micromolar IC(50) values
      versus E. coli MurB and submicromolar minimal inhibitory concentrations (MIC)
      against Staphylococcus aureus GC 1131, Enterococcus faecalis GC 2242,
      Streptococcus pneumoniae GC 1894, and E. coli GC 4560 imp, a strain with
      increased outer membrane permeability. None of these compounds show antimicrobial
      activity against Candida albicans, a marker of eukaryotic toxicity. Moreover,
      these compounds inhibit peptidoglycan biosynthesis, as assessed by measuring the
      amount of soluble peptidoglycan produced by Streptococcus epidermidis upon
      incubation with compounds. A partial least squares projection to latent
      structures analysis shows that improving MurB potency and MIC values correlate
      with increasing lipophilicity of the C-4 substituent of the 5-hydroxy-1H-pyrazol
      3(2H)-one core. Docking studies using FLO and PharmDock produced several binding
      orientations for these molecules in the MurB active site.

PMID- 17004715
TI  - Structural investigation of the 7-chloro-3-hydroxy-1H-quinazoline-2,4-dione
      scaffold to obtain AMPA and kainate receptor selective antagonists. Synthesis,
      pharmacological, and molecular modeling studies.
AB  - In this paper, the study of new 7-chloro-3-hydroxy-1H-quinazoline-2,4-dione
      derivatives, designed as AMPA and kainate (KA) receptor antagonists, is reported.
      Some derivatives bear different carboxy-containing alkyl chains on the 3-hydroxy
      group, while various heterocyclic rings or amide moieties are present at the 6
      position of other compounds. Binding data at Gly/NMDA, AMPA, and high-affinity KA
      receptors showed that the presence of the free 3-hydroxy group is of paramount
      importance for a good affinity at all three investigated receptors, while
      introduction of some 6-heterocyclic moieties yielded AMPA-selective antagonists.
      The most significant result was the finding of the 6-(2-carboxybenzoylamino)-3
      hydroxy-1H-quinazolin-2,4-dione 12, which possesses good affinity for high
      affinity and low-affinity KA receptors (Ki=0.62 microM and 1.6 microM,
      respectively), as well as good selectivity. To rationalize the trend of
      affinities of the reported derivatives, an intensive molecular modeling study was
      carried out by docking compounds to models of the Gly/NMDA, AMPA, and KA
      receptors.

PMID- 17004717
TI  - Simplified analogues of immucillin-G retain potent human purine nucleoside
      phosphorylase inhibitory activity.
AB  - A set of deazaguanine derivatives 1-3 targeting human purine nucleoside
      phosphorylase (hPNP) have been designed and synthesized. The new compounds are
      characterized by the presence of a structurally simplified "azasugar" motif to be
      more easily accessible by chemical synthesis than previous inhibitors. In the
      enzymatic assays, some of the new derivatives proved to be able to inhibit hPNP
      at low nanomolar concentration, thereby showing the same inhibitory potency in
      vitro as immucillin-H (IMH). Molecular docking experiments revealed a binding
      mode to hPNP essentially identical to that of IMH. As a result, the lower in vivo
      activity exhibited by 1d, compared with that exhibited by IMH, might be ascribed
      to differences in the pharmacokinetic, rather than pharmacodynamic, profile
      between these compounds. Derivatives 1a, 1d, and 2c emerged as the most active
      compounds within this new set and may represent interesting leads in the search
      for novel hPNP inhibitors.

PMID- 17004719
TI  - Stabilization of a native protein mediated by ligand binding inhibits amyloid
      formation independently of the aggregation pathway.
AB  - The acylphosphatases from Sulfolobus solfataricus and Drosophila melanogaster
      (Sso AcP and AcPDro2) were previously shown to form amyloid-like aggregates
      without the need to unfold initially. Inorganic phosphate (Pi), a competitive
      inhibitor binding specifically to the active site of these proteins, was found to
      stabilize, upon binding, the native state of AcPDro2 and to inhibit its
      conversion into amyloid-like fibrils. The inhibitory effect of Pi is suppressed
      only in a variant in which the Arg residue responsible for Pi binding is mutated.
      The study on Sso AcP shows that Pi retards both the formation of the initial
      nativelike oligomers and their subsequent conversion into protofibrils. Thus,
      stabilization of the native structure mediated by specific binding with small
      molecules can be an effective therapeutic strategy against protein deposition
      diseases that originate from initially folded proteins, independently of the
      structure of the protein, its aggregation pathway, and the particular aggregated
      species responsible for pathogenesis.

PMID- 17004718
TI  - Synthesis and biological properties of novel, uracil-containing histone
      deacetylase inhibitors.
AB  - A novel series of compounds containing a uracil moiety as the connection unit
      between a phenyl/phenylalkyl portion and a N-hydroxy-polymethylenealkanamide or 
      methylenecinnamylamide group (uracil-based hydroxamic acids, UBHAs) was tested
      against maize histone deacetylases (HDACs) and mouse HDAC1. Compounds with a
      phenyl/benzyl ring at the uracil-C6 position and bearing 4-5 carbon units as well
      as a m- or p-methylenecinnamyl moiety as a spacer were the most potent
      inhibitors. In cell-based human HDAC1 and HDAC4 assays, the two UBHAs tested
      inhibited the HDAC1 but not HDAC4 immunoprecipitate activity. When tested in
      human leukemia U937 cells, some UBHAs produced G1 phase arrest of the cell cycle.
      Moreover, 1j showed high antiproliferative and dose-dependent granulocytic
      differentiation properties. The tested UBHAs displayed weak p21WAF1/CIP1
      induction in U937 cells, and 1d and 1j showed high histone H3 and alpha-tubulin
      acetylation effects.

PMID- 17004720
TI  - Reactions of artemisinin and arteether with acid: implications for stability and
      mode of antimalarial action.
AB  - The currently accepted mechanism of trioxane antimalarial action involves
      generation of free radicals within or near susceptible sites probably arising
      from the production of distonic radical anions. An alternative mechanistic
      proposal involving the ionic scission of the peroxide group and consequent
      generation of a carbocation at C-4 has been suggested to account for antimalarial
      activity. We have investigated this latter mechanism using DFT (B3LYP/6-31+G*
      level) and established the preferred Lewis acid protonation sites (artemisinin
      O5a>>O4a approximately O3a>O2a>O1a; arteether O4a>or=O3a>O5b>>O2a>O1a; Figure 3)
      and the consequent decomposition pathways and hydrolysis sites. In neither
      molecule is protonation likely to occur on the peroxide bond O1-O2 and therefore
      lead to scission. Therefore, the alternative radical pathway remains the
      likeliest explanation for antimalarial action.

PMID- 17004721
TI  - Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)
      [[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6
      dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective,
      potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: a potential
      therapeutic agent for the treatment of hepatitis C infection.
AB  - Hepatitis C virus (HCV) infection is the major cause of chronic liver disease,
      leading to cirrhosis and hepatocellular carcinoma, which affects more than 170
      million people worldwide. Currently the only therapeutic regimens are
      subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone
      or in combination with oral ribavirin. Although combination therapy is reasonably
      successful with the majority of genotypes, its efficacy against the predominant
      genotype (genotype 1) is moderate at best, with only about 40% of the patients
      showing sustained virological response. Herein, the SAR leading to the discovery
      of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease
      inhibitor that has been advanced to clinical trials in human beings for the
      treatment of hepatitis C viral infections is described. X-ray structure of
      inhibitor 70 complexed with the NS3 protease and biological data are also
      discussed.

PMID- 17004722
TI  - Multivalent effects of RGD peptides obtained by nanoparticle display.
AB  - The binding of RGD peptides to integrins offers an excellent system to study the
      multivalent mediated changes in affinity that arise when peptides, displayed on
      the surface of a nanoparticle carrier, bind to integrins displayed on the cell
      membrane. The IC50 of an RGD nanoparticle for endothelial adhesion was 1.0 nM
      nanoparticle or 20 nM peptide (20 peptide/nanoparticle) and was associated with
      strong multivalent effects, defined as a multivalent enhancement factor (MVE) of
      38 (MVE=IC50 (peptide)/IC50 (peptide when displayed by nanoparticle)). The
      attachment of RGD peptides to nanoparticles resulted in an extension of the
      peptide blood half-life from 13 to 180 min. Based on the multivalent enhancement
      of affinity and extension of blood half-life, multivalent RGD nanoparticle-sized
      materials should be potent inhibitors of the alpha(V)beta(3) function on
      endothelial cells in vivo.

PMID- 17004723
TI  - Evaluation of azasterols as anti-parasitics.
AB  - In this article, the design and synthesis of some novel azasterols is described,
      followed by their evaluation against Trypanosoma brucei rhodesiense, T. cruzi,
      Leishmania donovani, and Plasmodium falciparum, the causative agents of human
      African trypanosomiasis, Chagas disease, leishmaniasis, and malaria,
      respectively. Some of the compounds showed anti-parasitic activity. In
      particular, a number of compounds appeared to very potently inhibit the growth of
      the blood stream form T. b. rhodesiense, with one compound giving an IC50 value
      of 12 nM. Clear structure activity relationships could be discerned. These
      compounds represent important leads for further optimization. Azasterols have
      previously been shown to inhibit sterol biosynthesis in T. cruzi and L. donovani
      by the inhibition of the enzyme sterol 24-methyltransferase. However, in this
      case, none of the compounds showed inhibition of the enzyme. Therefore, these
      compounds have an unknown mode of action.

PMID- 17004724
TI  - Structural determinants of opioid activity in derivatives of 14-aminomorphinones:
      effects of changes to the chain linking of the C14-amino group to the aryl ring.
AB  - The 14-aminodihydromorphinone and codeinone series of opioid ligands have
      produced a number of ligands of substantial interest. To investigate the
      importance of the 14-substituent, a series of analogues in which the side chain
      length is varied and the amide and alkene functions are reduced have been
      prepared. Binding affinity, particularly at the mu-opioid receptor (MOR), was
      largely determined by the aromatic group of the side chain. In the [35S]GTPgammaS
      functional assay, the ligands having a three-carbon side chain were more potent
      antagonists than their longer chain counterparts, while shorter, two-carbon chain
      analogues were of higher MOR efficacy, an effect that was confirmed in vivo. Wash
      resistant binding was observed within this series and appeared to be unrelated to
      side-chain length.

PMID- 17004725
TI  - Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and
      evaluation for beta-amyloid plaque imaging.
AB  - Alzheimer's disease (AD) is pathologically characterized by the accumulation of
      amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo
      imaging of plaques and tangles would be beneficial for the early diagnosis of AD.
      It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6
      heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of
      AD in India. In the present study, eight novel derivatives of curcumin and 4-(4
      hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and
      their binding affinities for beta-amyloid (Abeta) aggregates were measured. Of
      these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding
      affinity (Ki=0.07 nM), and therefore, 8 was radiolabeled and evaluated as a
      potential probe for Abeta plaque imaging. Partition coefficient measurement and
      biodistribution in normal mice demonstrated that [18F]8 has a suitable
      lipophilicity and reasonable initial brain uptake. Metabolism studies also
      indicated that [18F]8 is metabolically stable in the brain. These results suggest
      that [18F]8 is a suitable radioligand for Abeta plaque imaging.

PMID- 17004726
TI  - 9-{[3-fluoro-2-(hydroxymethyl)cyclopropylidene]methyl}adenines and -guanines.
      Synthesis and antiviral activity of all stereoisomers1.
AB  - All stereoisomers of adenine and guanine methylene-3-fluoromethylenecyclopropane
      analogues of nucleosides 9a, 9b, 10a, 10b, 11a, 11b, 12a, and 12b were
      synthesized and their antiviral activities were evaluated. A highly convergent
      approach permitted the synthesis of all these analogues using a single
      intermediate 15. Reaction of aldehyde 13 with fluorotrichloromethane and tri-n
      butylphosphine gave fluoroalkenes 14a+14b (83:17). Addition of carbene derived
      from ethyl diazoacetate gave cyclopropane 15 as the major product. Reduction
      (19), bromination (20), and phenylselenenylation (21), followed by Se oxidation
      and beta-elimination gave cis-methylenecyclopropane 22. Addition of bromine
      provided the reagent 23 for alkylation-elimination. Reaction of 23 with adenine
      led to an isomeric mixture 25a+26a that after deprotection afforded analogues 9a
      and 10a. The 2-amino-6-chloropurine furnished 25e+26e and after deblocking (9e
      and 10e) and hydrolysis gave targets 9b and 10b. Intermediate 15 provided, after
      debenzylation (27), 2-nitrophenylselenenylation (28), reduction (29), benzylation
      (30), and oxidation-elimination trans-methylenecyclopropane 31. Addition of
      bromine gave reagent 32. Further transformations followed the sequence outlined
      for analogues 9a, 9b, 10a, and 10b. Analogue 9b was effective against human
      cytomegalovirus (HCMV; Towne) with EC50 2.9 microM. The trans-isomer 10b
      inhibited AD169 strain of HCMV (EC50 15 microM) and the murine virus MCMV (EC50
      2.5 microM). Compound 12a was effective against Epstein-Barr virus (EC50<0.03
      microM). Analogue 9a inhibited varicella zoster virus (EC50 5.9 microM) and human
      immunodeficiency virus type 1 (EC50 5.2 microM). Analogues 9a, 10a, and 11a are
      moderate substrates for adenosine deaminase. The structure-activity relationships
      will be discussed in context with other methylenecyclopropane analogues.

PMID- 17004727
TI  - Heparin derivatives as inhibitors of BACE-1, the Alzheimer's beta-secretase, with
      reduced activity against factor Xa and other proteases.
AB  - Heparan sulfate (HS) regulates processing of the amyloid precursor protein by the
      Alzheimer's beta-secretase (BACE-1). An HS analogue, porcine intestinal mucosal
      heparin, was systematically modified at the principal positions of O-sulfation
      and N-sulfation/acetylation and tested for BACE-1 inhibitory and anti factor Xa
      activities. The derivative with the highest anti-BACE-1 to anti-Xa activity ratio
      contained N-acetyl and 2-O- and 6-O-sulfates and also exhibited attenuated
      activities against cathepsin-D and renin, two other structurally related aspartyl
      proteases.

PMID- 17004729
TI  - Pseudo-Jahn-Teller effect as the origin of the exalted frequency of the b2u
      Kekule mode in the 1(1)B2u excited state of benzene.
AB  - In this paper we show that a pseudo-Jahn-Teller (PJT) coupling between the (1)A1g
      ground state and the (1)B2u excited states along the Kekule mode of b2u symmetry
      is responsible for the surprisingly low frequency of this mode in the ground
      state and its remarkable upward shift of 261 cm(-1) upon excitation to the first
      (1)B2u excited state.

PMID- 17004728
TI  - Design, synthesis, and incorporation of a beta-turn mimetic in angiotensin II
      forming novel pseudopeptides with affinity for AT1 and AT2 receptors.
AB  - A benzodiazepine-based beta-turn mimetic has been designed, synthesized, and
      incorporated into angiotensin II. Comparison of the mimetic with beta-turns in
      crystallized proteins showed that it most closely resembles a type II beta-turn.
      The compounds exhibited high to moderate binding affinity for the AT2 receptor,
      and one also displayed high affinity for the AT1 receptor. Molecular modeling
      showed that the high-affinity compounds could be incorporated into a previously
      derived model of AT2 receptor ligands.

PMID- 17004730
TI  - Quantum simulation of solution phase intramolecular electron transfer rates in
      betaine-30.
AB  - Mixed quantum-classical atomistic simulations have been carried out to
      investigate the mechanistic details of excited state intramolecular electron
      transfer in a betaine-30 molecule in acetonitrile. The key electronic degrees of
      freedom of the solute molecule are treated quantum mechanically using the
      semiempirical Pariser-Parr-Pople Hamiltonian, including the solvent influence on
      electronic structure. The intramolecular vibrational modes are also treated
      explicitly at a quantum level, with the remaining elements treated classically
      using empirical potentials. The electron-transfer rate, corresponding to S1 -->
      S0 relaxation, is evaluated via time-dependent perturbation theory with the
      explicit inclusion of the dynamics of solvation and intramolecular conformation.
      The calculations reveal that, while solvation dynamics is critical to the rate,
      the intramolecular torsional dynamics also plays an important role. The
      importance of the use of multiple high-frequency quantum modes is also discussed.

PMID- 17004731
TI  - Energy-flow dynamics in the molecular channel of propanal photodissociation,
      C2H5CHO --> C2H6 + CO: direct ab initio molecular dynamics study.
AB  - Direct ab initio molecular dynamics calculations have been carried out for the
      molecular channel of the photodissociation of propanal, C2H5CHO --> C2H6 + CO, at
      the RMP2(full)/cc-pVDZ level of ab initio molecular orbital theory. The initial
      conditions were generated using the microcanonical sampling to put the excess
      energy randomly into all vibrational modes of the TS. Starting from the TS, a
      total of approximately 700 trajectories were numerically integrated for 100 fs.
      The obtained final energy distributions for the C2H6 and CO fragments and their
      relative translational motion were found to be quite similar to those obtained
      for the acetaldehyde reaction, CH3CHO --> CH4 + CO, in our previous study (Chem.
      Phys. Lett. 2006, 421, 549) despite the fact that the number of degree of freedom
      for C2H6 is larger than that for CH4. The coupling between the intrinsic reaction
      coordinate and one of the generalized normal modes orthogonal to it was predicted
      substantially strong around s = 1.4 amu(1/2) bohr, and it is expected that the
      energy flow out of C2H6 proceeds through this coupling. However, the obtained
      energy distributions strongly suggest that the coupling among the modes in C2H6
      is quite small and the intramolecular energy redistribution does not occur
      efficiently in this molecule.

PMID- 17004732
TI  - On the ultrafast infrared spectroscopy of anion hydration shell hydrogen bond
      dynamics.
AB  - Molecular Dynamics simulations are used to examine the title issue for the I
      /HOD/D2O solution system in connection with recent ultrafast infrared
      spectroscopic experiments. It is argued that the long "modulation time"
      associated with the spectral diffusion of the OH frequency, extracted in these
      experiments, should be interpreted as reflecting the escape time of an HOD from
      the first hydration shell of the I- ion, i.e., the residence time of an HOD in
      this solvation shell. Shorter time features related to the oscillation of the OH
      ...I- hydrogen bond and the breaking and making of this bond are also discussed.

PMID- 17004733
TI  - Study of the structure, energetics, and vibrational properties of small ammonia
      clusters (NH3)n (n = 2-5) using correlated ab initio methods.
AB  - Equilibrium geometries, interaction energies, and harmonic frequencies of (NH3)n
      isomers (n = 2-5) have been computed using correlated calculations (MP2) in
      conjunction with Dunning's aug-cc-pVXZ (X = D, T, Q) basis sets and the
      Counterpoise procedure. Whenever available, literature values for the binding
      energy and geometry of dimers and trimers agree well with our data. Low lying
      isomers for (NH3)4 and (NH3)5 have been found to have similar binding energies
      (roughly 16 and 20 kcal/mol for the tetramer and pentamer, respectively), perhaps
      suggesting the presence of a very smooth energy landscape. Using BSSE corrected
      forces or freezing the monomer structure to its gas phase geometry have been
      found to have only a weak impact on the energetic and structural properties of
      the clusters. The effect of zero-point energy (ZPE) on the relative stability of
      the clusters has been estimated using harmonic frequencies. The latter also
      highlighted the presence of vibrational fingerprints for the presence of double
      acceptor ammonia molecules. Many-body effects for (NH3)n isomers (n = 2-4) have
      been investigated to explore the possibility of building a pairwise interaction
      model for ammonia. In the frame of the work presented, we have found the 3-body
      effect to account for 10-15% of the total interaction energy, whereas the 4-body
      effects may be neglected as first approximation.

PMID- 17004734
TI  - Symmetry properties of vibrational modes in mesoporphyrin IX dimethyl ester
      investigated by polarization-sensitive resonance Raman and CARS spectroscopy.
AB  - The symmetry properties of selected vibrational modes of mesoporphyrin IX
      dimethyl ester (MP-IX-DME) in solution are investigated under different
      electronic resonance conditions. The Raman band parameters of the macrocycle
      modes nu(2), nu(10), nu(11), and nu(19) are determined from a quantitative
      analysis of polarized spontaneous resonance Raman (RR) and polarization-sensitive
      (PS) multiplex coherent anti-Stokes Raman scattering (CARS) spectra obtained with
      pre-resonant B band and resonant Qx band excitation, respectively. Additionally,
      the molecular geometry and the vibrational modes of MP-IX-DME are calculated by
      employing density functional theory (DFT) on the B3LYP/6-31G(d) level. Both the
      DFT-derived structure and the Raman spectroscopic parameters of MP-IX-DME
      indicate minor deviations from an ideal D2h macrocycle symmetry. To assess the
      influence of the beta substitution pattern on the in-plane symmetry, calculated
      normal-mode vectors and several experimentally detected parameters, such as peak
      positions, depolarization ratios, and coherent phases, are analyzed. The effects
      of the macrocycle substitution pattern are different for the selected vibrational
      modes: nu(2) in particular is very sensitive to subtle perturbations of the in
      plane symmetry. The considerable activity of totally symmetric vibrations
      observed in the PS CARS spectra of MP-IX-DME and the correlation of mode
      symmetries with coherent phases confirm earlier PS CARS results on
      octaethylporphine (OEP) acquired under the same electronic resonance conditions.

PMID- 17004735
TI  - The K2 2(3)Pi(g) state: new observations and analysis.
AB  - Totally 3045 transitions into the 2(3)Pi(g) v = 0-42, J = 0-103, Omega = 0, 1, 2
      rovibrational levels have been observed by infrared-infrared double resonance
      fluorescence excitation and two-photon spectroscopy. Molecular constants
      including the spin-orbit interaction parameters are obtained. Although the K2
      2(3)Pi(g) state dissociates to the 4s + 3d atomic limit, it is strongly mixed
      with the 3P ionic states in the range of the potential well. This mixing results
      in a relatively large equilibrium internuclear distance Re = 5.254 A and a larger
      spin-orbit constant A0 approximately 14.17 cm(-1) than that of the atomic limit 
      2.33 cm(-1). Strong perturbations of the 2(3)Pi(g) levels observed are attributed
      to the spin-orbit coupling with the 4(1)Sigma(g)+ state.

PMID- 17004736
TI  - Chemical dynamics of the formation of the 1,3-butadiynyl radical (C4H(X2Sigma+))
      and its isotopomers.
AB  - The reaction of dicarbon molecules in their electronic ground, C2(X1Sigma(g)+),
      and first excited state, C2(a3Pi(u)), with acetylene, C2H2(X1Sigma(g)+), to
      synthesize the 1,3-butadiynyl radical, C4H(X2Sigma+), plus a hydrogen atom was
      investigated at six different collision energies between 10.6 and 47.5 kJ mol(-1)
      under single collision conditions. These studies were contemplated by crossed
      molecular beam experiments of dicarbon with three acetylene isotopomers
      C2D2(X1Sigma(g)+), C2HD (X1Sigma+), and 13C2H2(X1Sigma(g)+) to elucidate the role
      of intersystem crossing (ISC) and of the symmetry of the reaction intermediate(s)
      on the center-of-mass functions. On the singlet surface, dicarbon was found to
      react with acetylene through an indirect reaction mechanism involving a
      diacetylene intermediate. The latter fragmented via a loose exit transition state
      via an emission of a hydrogen atom to form the 1,3-butadiynyl radical
      C4H(X2Sigma+). The D(infinity)(h) symmetry of the decomposing diacetylene
      intermediate results in collision-energy invariant, isotropic (flat) center-of
      mass angular distributions of this microchannel. Isotopic substitution
      experiments suggested that at least at a collision energy of 29 kJ mol(-1), the
      diacetylene isotopomers are long-lived with respect to their rotational periods.
      On the triplet surface, the reaction involved three feasible addition complexes
      located in shallower potential energy wells as compared to singlet diacetylene.
      The involvement of the triplet surface accounted for the asymmetry of the center
      of-mass angular distributions. The detection of the 1,3-butadiynyl radical,
      C4H(X2Sigma+), in the crossed beam reaction of dicarbon molecules with acetylene
      presents compelling evidence that the 1,3-butadiynyl radical can be formed via
      bimolecular reactions involving carbon clusters in extreme environments such as
      circumstellar envelopes of dying carbon stars and combustion flames.

PMID- 17004737
TI  - Noise perturbation in functional principal component analysis filtering for two
      dimensional correlation spectroscopy: its theory and application to infrared
      spectra of a poly(3-hydroxybutyrate) thin film.
AB  - A method based on noise perturbation in functional principal component analysis
      (NPFPCA) is for the first time introduced to overcome the noise interference
      problem in two-dimensional correlation spectroscopy (2D-COS). By the systematic
      addition of synthetic noise to the dynamic multivariate spectral data, the
      functional principal component analysis (FPCA) described in this report is able
      to accurately determine which eigenvectors are representing significant signals
      instead of noise in the original data. This feature is especially useful for the
      data reconstruction and noise filtering. Reconstructed data resulted from the
      smooth eigenvectors can produce much more reliable 2D correlation spectra by
      removing the correlation artifacts from noise, which in turn enable more accurate
      interpretation of the spectral variations. The usefulness of this method is
      demonstrated with a theoretical framework and applications to the 2D correlation
      analyses of both simulated data and temperature-dependent reflection-absorption
      infrared spectra of a poly(3-hydroxybutyrate) (PHB) thin film.

PMID- 17004738
TI  - Solvent effects on the S0(1(1)Ag-) --> S2(1(1)Bu+) transition of beta-carotene,
      echinenone, canthaxanthin, and astaxanthin in supercritical CO2 and CF3H.
AB  - Solvent-induced spectral shifts of the four C40 carotenoids, beta-carotene,
      echinenone, canthaxantin, and astaxanthin, have been studied in supercritical CO2
      and CF3H. In situ absorption spectroscopic analysis was used to determine the
      maximum peak position of the electronic transitions from the ground state (1(1)Ag
      ) to the S2 state (1(1)Bu+) of the carotenoids. The medium polarizability
      function, R(n) = (n2 - 1)/(n2 + 2) of the refractive index of the solvent was
      varied over the range R(n) = 0.08-0.14, by changing the pressure of CO2 or CF3H
      between 90 and 300 bar at the temperature 308 K. For all the carotenoids studied
      here, a significant hypsochromic shift of ca. 20-30 nm was observed in
      supercritical fluids as compared to that in nonpolar liquids. The spectral shifts
      in supercritical fluids were compared with those in liquids and showed a clear
      linear dependence on the medium polarizability. The temperature-dependent shift
      of the absorption maxima was less significant. Interestingly, there was almost no
      difference in the energetic position of the absorption maxima in supercritical
      CO2 and CF3H at a given R(n) value. This is in contrast to previous
      extrapolations from studies in liquids at larger R(n) values, which yielded
      different slopes of the R(n)-dependent spectral shifts for polar and nonpolar
      solvents toward the gas-phase limit of R(n) = 0. The current experimental results
      in the gas-to-liquid range show that the polarity of the solvent has only a minor
      influence on the 1(1)Ag- --> 1(1)Bu+ transition energy in the region of low R(n).
      We also obtain more reliable extrapolations of this 0-0 transition energy to the
      gas-phase limit nu(0-0)(gas-phase) approximately (23,000 +/- 120) cm(-1) for beta
      carotene.

PMID- 17004739
TI  - Primary mechanism of the thermal decomposition of tricyclodecane.
AB  - To better understand the thermal decomposition of polycyclanes, the pyrolysis of
      tricyclodecane has been studied in a jet-stirred reactor at temperatures from 848
      to 933 K, for residence times between 0.5 and 6 s and at atmospheric pressure,
      corresponding to a conversion between 0.01% and 25%. The main products of the
      reaction are hydrogen, methane, ethylene, ethane, propene, 1,3-cyclopentadiene,
      cyclopentene, benzene, 1,5-hexadiene, toluene, and 3-cyclopentylcyclopentene. A
      primary mechanism containing all the possible initiation steps, including those
      involving diradicals, as well as propagation reactions has been developed and
      allows experimental results to be satisfactorily modeled. The main reaction
      pathways of consumption of tricyclodecane and of formation of the main products
      have been derived from flow rate and sensitivity analyses.

PMID- 17004740
TI  - Absolute rate coefficients and branching percentages for the reactions of POxCly-
      + N (4S(3/2)) and POxCly- + O (3P) at 298 K in a selected-ion flow tube
      instrument.
AB  - The absolute rate coefficients and product ion branching percentages at 298 K for
      the reactions of several POxCly- species with atomic nitrogen (N (4S(3/2))) and
      atomic oxygen (O (3P)) have been determined in a selected-ion flow tube (SIFT)
      instrument. POxCly- ions are generated by electron impact on POCl3 in a high
      pressure source. O atoms are generated by quantitative titration of N atoms with
      NO, where N atoms are produced by microwave discharge on N2. The experimental
      procedure allows for the determination of rate coefficients for the reaction of
      the reactant ion with N (4S(3/2)) and O (3P) as well as with N2 and NO. None of
      the ions react with N2 or NO, giving an upper limit to the rate coefficient of <5
      x 10(-12) cm3 molecules(-1) s(-1). POCl3- and POCl2- do not react with N atoms,
      giving an upper limit to the rate coefficient of <1 x 10(-11) cm3 molecules(-1)
      s(-1). The major product ion for POCl3- and POCl2- reacting with O involves loss
      of Cl from the reactant ion, accounting for >85% of the products. PO2- is a minor
      product (<or=4%) from POCl2- + O. Only PO2Cl- reacts with both N and O, directly
      giving PO2- and PO3- as major products. In addition, calculations of the
      structures and energies for PO2N, PO2N-, and NCl have been performed at the G3
      level of theory to obtain estimates for the energetics of the PO2Cl- reactions.
      PO2-, PO3-, and PO2Cl2- are all unreactive with both N and O. Comparisons of the
      reactivity of POxCly- ions with O atoms are made to previous reactivity studies
      of these ions. In particular, routes that yield the very stable PO2- and PO3-
      ions are discussed.

PMID- 17004741
TI  - Comparative study of the hypercoordinate ions C7H9+ and C8H9+ by the ab
      initio/GIAO-CCSD(T) method.
AB  - A comparative study of the hypercoordinate square-pyramidal carbocations C7H9+
      and C8H9+ was performed by the ab initio/GIAO-CCSD(T) method. The structures and
      13C NMR chemical shifts of the cations were calculated at the GIAO
      CCSD(T)/tzp/dz//MP2/cc-pVTZ level. The bishomo square pyramidal structure 1 was
      calculated for C7H9+ at the MP2/cc-pVTZ level. The calculated 13C NMR chemical
      shifts of structure 1 agree extremely well with the experimental values. However,
      unlike for C7H9+ both the bishomo square pyramidal structure 3 and the
      trishomocyclopropenium type structure 4 were found to be minima on the potential
      energy surface of C8H9+. They are very close energetically with cation 3, only
      0.7 kcal/mol less stable than cation 4 at the MP2/cc-pVTZ//MP2/cc-pVTZ + ZPE
      level. Neither structure 3 nor 4 yields NMR spectra that agree with experiment.
      However, a weighted average of the two reproduces the observed NMR spectrum of
      C8H9+ (at -80 degrees C) quite well.

PMID- 17004742
TI  - Structural and electronic analysis of lanthanide complexes: reactivity may not
      necessarily be independent of the identity of the lanthanide atom--a DFT study.
AB  - Density functional theory calculations were used to study a given complex for the
      whole series of lanthanide cations: [Ln(C3H5)Cp(OMe)] (1) [Ln = La (Z = 57)-Lu (Z
      = 71)], the radioactive lanthanide promethium (Z = 61) excepted. Contrary to the
      common assumptions, the calculations suggested a significant, albeit indirect,
      contribution of f electrons to bonding. Relativistic effects were considered in
      the calculations of the bonding energies, as well as in geometry optimizations in
      both spin-restricted and unrestricted formalisms. The unrestricted orbitals were
      finally used for the analysis of the charges and the composition of the frontier
      orbitals. It was confirmed that the ionic character was more pronounced for
      complexes of the late lanthanides.

PMID- 17004743
TI  - Estimation of electronegativity values of elements in different valence states.
AB  - The electronegativities of 82 elements in different valence states and with the
      most common coordination numbers have been quantitatively calculated on the basis
      of an effective ionic potential defined by the ionization energy and ionic
      radius. It is found that for a given cation, the electronegativity increases with
      increasing oxidation state and decreases with increasing coordination number. For
      the transition-metal cations, the electronegativity of the low-spin state is
      higher than that of the high-spin state. The ligand field stabilization, the
      first filling of p orbitals, the transition-metal contraction, and especially the
      lanthanide contraction are well-reflected by the relative values of our proposed
      electronegativity. This new scale is useful for us to estimate some quantities
      (e.g., the Lewis acid strength for the main group elements and the hydration free
      energy for the first transition series) and predict the structure and property of
      materials.

PMID- 17004744
TI  - Structure absorption spectra correlation in a series of 2,6-dimethyl-4
      arylpyrylium salts.
AB  - A combined experimental and theoretical study of the absorption spectra of a
      group of closely related pyrylium perchlorates 1-11 are presented. Minor changes
      in the position of the substituents lead to drastic changes in the absorption
      spectra in this series of compounds. We have attempted to explain the observed
      changes using the x,y-band notation developed by Balaban and co-workers.
      Absorption spectra of all compounds are compared with results from time-dependent
      density functional theory (TDDFT) and Zerner's intermediate neglect of
      differential overlap (ZINDO/S) level calculations. Results of the calculations
      are in good agreement with experimental observations and an interesting
      correlation between Balaban's notations and the MO transitions are obtained for
      simple derivatives. It is suggested that for more complex systems such as alpha-
      and beta-naphthyl substituted systems, the empirical method is not appropriate.

PMID- 17004745
TI  - Experimental and density functional theory study of the vibrational properties of
      2-mercaptobenzimidazole in interaction with gold.
AB  - The vibrational properties of the 2-mercaptobenzimidazole (MBI) molecule in
      interaction with gold were examined by a combined approach of FTIR measurements
      and density functional theory (DFT). A complete assignment of the 42 normal modes
      of MBI has been performed on the basis of DFT calculations at the B3PW91 level in
      complement to the Raman and FTIR spectra. Calculations demonstrated that, on the
      deprotonated MBI molecule, the negative charge is localized on the sulfur atom,
      favoring the formation of a gold-sulfur bond upon reaction of MBI with gold. This
      was confirmed by the very good agreement between the calculated spectrum and the
      experimental spectra of different gold-MBI compounds, indicating that the
      vibrational properties of adsorbed MBI are chiefly determined by the coordination
      through the sulfur atom.

PMID- 17004746
TI  - Characterization of electronic transition energies and trigonal distortion of the
      (FeO6)9- coordination complex in the Al2O3:Fe3+ system: a simple method for
      transition-metal ions in a trigonal ligand field.
AB  - A theoretical method for studying the inter-relationships between electronic and
      molecular structure has been proposed on the basis of the complete energy
      matrices of electron-electron repulsion, the ligand field, and the spin-orbit
      coupling for the d5 configuration ion in a trigonal ligand field. As an
      application, the local distortion structure and temperature dependence of zero
      field splitting for Fe3+ ions in the Al2O3:Fe3+ system have been investigated.
      Our results indicate that the local lattice structure of the (FeO6)(9-)
      octahedron in the Al2O3:Fe3+ system has an elongated distortion and the value of
      distortion is associated with the temperature. The elongated distortion may be
      attributed to the facts that the Fe3+ ion has an obviously larger ionic radius
      than the Al3+ ion and the Fe3+ ion will push the two oxygen triangles upward and
      downward, respectively, along the 3-fold axis. By diagonalizing the complete
      energy matrices, we found that the theoretical results of electronic transition
      energies and EPR spectra for Fe3+ ions in the Al2O3:Fe3+ system are in good
      agreement with the experimental findings. Moreover, to understand the detailed
      physical and chemical properties of the Al2O3, the theoretical values of the zero
      field splitting parameters and the corresponding distortion parameters in the
      range 50 K <or= T <or= 250 K are reported first.

PMID- 17004747
TI  - The SPASIBA force field for chondroitin sulfate: vibrational analysis of D
      glucuronic and N-acetyl-D-galactosamine 4-sulfate sodium salts.
AB  - Normal-mode analyses were carried out on the two components of the chondroitin 4
      sulfate linear glycosaminoglycan, a copolymer implying alternate D-glucuronate
      beta-(1-->3) and N-acetyl-D-galactosamine 4-sulfate beta-(1-->4) (hereafter named
      D-galactosamine 4-sulfate) residues. Scaled quantum mechanical calculations (SQM)
      using the density functional theory approach at different levels of theory
      (B3LYP/6-31G** and B3LYP/6-31++G**) were performed to obtain correct vibrational
      assignments. The SPASIBA empirical force field parameters were then obtained from
      both theoretical predictions and observed IR and Raman data. It is shown that
      calculations including diffuse functions at the B3LP/6-31++G** level and the
      introduction of the Na+ counterion are necessary to give correct assignments of
      the CO2- symmetric (nu(s)) and antisymmetric (nu(a)) stretching modes for the
      glucuronic carboxylate residue.

PMID- 17004748
TI  - Ab initio procedure for aqueous-phase pKa calculation: the acidity of nitrous
      acid.
AB  - We present an ab initio procedure for accurately calculating aqueous-phase pKa
      values and apply it to study the acidity of nitrous acid (HNO2, or HONO). The
      aqueous-phase pK(a) of nitrous acid was obtained from calculated gas-phase
      acidities and solvation free energies via a thermodynamic cycle and the solvation
      model chemistry of Barone et al. (J. Chem. Phys. 1997, 107, 3210). Solvation free
      energies were calculated at the HF/6-31G(d) level using the dielectric
      polarizable continuum and the integral equation formalism-polarizable continuum
      solvent models (D-PCM and IEF-PCM, respectively), with the D-PCM model yielding
      the most accurate pKa values. For HF free energies of solvation, significant
      improvements in accuracy could be made by moving to the larger 6-311++G(3df,3pd)
      and aug-cc-pVQZ basis sets. Solvation free energies were also calculated using
      the density functional theory (DFT) methods B3LYP, TPSS, PBE0, B1B95, VSXC, B98
      and O3LYP, with the most accurate methods being TPSS and VSXC, which provided
      average errors of less than 0.11 pKa units. Solvation free energies calculated
      with the different DFT methods were relatively insensitive to the basis set used.
      Our theoretical calculations are compared with experimental results obtained
      using stopped flow spectrophotometry. The pKa of nitrous acid was measured as
      3.16 at 25 degrees C, and the enthalpy and entropy of nitrous acid dissociation
      were calculated from measurements as 6.7 kJ mol(-1) and -38.4 J mol(-1) K(-1),
      respectively, between 25 and 45 degrees C. The UV/visible absorption spectra of
      the nitrite ion and nitrous acid were also examined, and molar extinction
      coefficients were obtained for each.

PMID- 17004749
TI  - Configuration-specific kinetic theory applied to an ideal binary gas mixture.
AB  - This paper is the second in a two-part series dealing with the configuration
      specific analyses for molecular collision events of hard, spherical molecules at
      thermal equilibrium. The first paper analyzed a single-component system, and the
      reader is referred to it for the fundamental concepts. In this paper, the
      expressions for the configuration-specific collision frequencies and the average
      line-of-centers collision angles and speeds are derived for an ideal binary gas
      mixture. The analyses show that the average line-of-centers quantities are all
      dependent upon the ratio of the masses of the two components, but not upon
      molecular size. Of course, the configuration-specific collision frequencies do
      depend on molecular size. The expression for the overall binary collision
      frequency is a simple sum of the configuration-specific collision frequencies and
      is identical to the conventional expression.

PMID- 17004750
TI  - Electrical property of Mo-doped VO2 nanowire array film by melting-quenching sol
      gel method.
AB  - Mo-doped VO(2) nanowire array film with good thermochromic properties was
      prepared by melting-quenching followed by heat treatment in a vacuum. The
      formation of the new microstructure is related to the cleavage of the oxide
      lamella along (001) and (100) plane with large interplanar spacing. Mo doping
      results in the loss of V(4+)-V(4+) pairs and destabilizes the semiconductor phase
      and consequently lowers the semiconductor-to-metal transition temperature T(c)
      from 64 to 42 degrees C. Because of enhancement of the electron concentration due
      to the presence of Mo donors, the Fermi level shifts toward the conduction band,
      resulting in the decrease of activation energy E(a), hence, temperature
      coefficient of resistance.

PMID- 17004751
TI  - Molecular water on exposed Al3+ cations is a source of acidity in silicoaluminas.
AB  - Evidence about the remarkable acidic nature of molecular water adsorbed at the
      surface of mesoporous MCM-41 silicoaluminas (MSA) with a ratio of Si/Al = 25 is
      reported, coming from both infrared spectroscopy and ab initio calculations. By
      using CO as a probe, OH stretching and HOH bending modes of water adsorbed on
      coordinatively unsaturated Al ions (Lewis sites) at the surface of MSA have been
      detected for the first time. CO adsorption causes OH stretching frequencies to
      suffer a bathochromic shift of about -200/-250 cm(-1), whereas the HOH bending
      frequency undergoes a hypsochromic shift by about +10/+20 cm(-1). B3LYP/6
      31+G(d,p) calculations on model clusters designed to mimic both Bronsted and
      Lewis sites validate the assignments, showing that water adsorbed on the surface
      Lewis site, when interacting with CO, shows an acidity comparable to that of a
      classical zeolitic Bronsted site.

PMID- 17004752
TI  - Tail ordering due to headgroup hydrogen bonding interactions in surfactant
      monolayers at the water-oil interface.
AB  - Interactions between surfactants, and the resultant ordering of surfactant
      assemblies, can be tuned by the appropriate choice of head- and tailgroups.
      Detailed studies of the ordering of monolayers of long-chain n-alkanoic and n
      alkanol monolayers at the water-vapor interface have demonstrated that rigid-rod
      all-trans ordering of the tailgroups is maintained upon replacing the alcohol
      with a carboxylic acid headgroup. In contrast, at the water-hexane liquid-liquid
      interface, we demonstrate that substitution of the -CH(2)OH with the -COOH
      headgroup produces a major conformational change of the tailgroup from disordered
      to ordered. This is demonstrated by the electron density profiles of triacontanol
      (CH(3)(CH(2))(29)OH) and triacontanoic acid (CH(3)(CH(2))(28)COOH) monolayers at
      the water-hexane interface, as determined by X-ray reflectivity measurements.
      Molecular dynamics simulations illustrate the presence of hydrogen bonding
      between the triacontanoic acid headgroups that is likely responsible for the tail
      ordering. A simple free energy illustrates the interplay between the attractive
      hydrogen bonding and the ordering of the tailgroup.

PMID- 17004753
TI  - Optimum hole-opening condition for Cisplatin incorporation in single-wall carbon
      nanohorns and its release.
AB  - We enclosed cisplatin (CDDP), an anticancer drug, inside single-wall carbon
      nanohorns (SWNH) with holes opened by being heated from room temperature to a
      target temperature (475-580 degrees C) in flowing dry air, with an increase rate
      of 1 degrees C/min. The optimum target temperature was found to be 500 degrees C,
      in terms of the least amount of CDDP deposited outside the SWNH, when the
      quantity of CDDP encapsulated inside the SWNH was 12 wt %. The incorporated CDDP
      was slowly released from the SWNH in phosphate buffer saline, and the released
      quantity was 80%, which was greatly improved from the previous value of 15%. This
      indicated that a CDDP-containing SWNH could become more potentially useful for
      biological applications.

PMID- 17004754
TI  - Catalyzed radical polymerization of styrene vapor on nanoparticle surfaces and
      the incorporation of metal and metal oxide nanoparticles within polystyrene
      polymers.
AB  - We present a novel approach to polymerize olefin vapors on the surfaces of
      metallic and semiconductor nanoparticles. In this approach, a free radical
      initiator such as AIBN is dissolved in a volatile solvent such as acetone.
      Selected nanoparticles (prepared separately using the laser vaporization
      controlled condensation method) are used to form initiator-coated nanoparticles
      placed on a glass substrate. The olefin (styrene) vapor is polymerized by the
      thermally activated initiator on the nanoparticle surfaces. Our approach also
      provides structural and mechanistic information on the early stages of catalyzed
      gas-phase polymerization, which can be used to correlate the gas-phase structural
      properties with the bulk properties and the performance of the polymer
      nanocomposites. This correlation is the key step in controlling the properties of
      the polymer nanocomposites. Our results clearly demonstrate the success of this
      method in preparing polymer coated nanoparticles for a variety of interesting
      applications. The precise control of the chemical functionality, thickness, and
      morphology of the polymer film and the size, size distribution, and properties of
      the core nanoparticles (photoluminescence, magnetic) may lead to major
      technological breakthroughs in a variety of applications including drug delivery,
      ultrasensitive detectors, and chemical and biological sensors.

PMID- 17004755
TI  - Direct solid-state NMR spectroscopic evidence for the NH4AlF4 crystalline phase
      derived from zeolite HY dealuminated with ammonium hexafluorosilicate.
AB  - Multinuclear (1)H, (19)F, and (27)Al MAS (magic angle spinning) and corresponding
      2D HETCOR (heteronuclear correlation) NMR spectroscopy, in combination with
      powder XRD measurements, provide the direct evidence for the NH(4)AlF(4)
      crystalline phase, which was formed from zeolite HY dealuminated with an aqueous
      (NH(4))(2)SiF(6) solution at 80 degrees C. The NH(4)AlF(4) crystalline phase
      exhibits a characteristic second-order quadrupolar-induced (27)Al NMR line shape
      spreading from 0 to -90 ppm (in a magnetic field of 11.7 T) and two (19)F
      resonances at -151 and -166 ppm in the (19)F NMR spectrum. An( 27)Al quadrupolar
      coupling constant (C(Q)) of 9.5 MHz and an asymmetry parameter (eta) of 0.1 were
      identified, for the first time, for the NH(4)AlF(4) crystalline phase observed.
      On the basis of the (19)F{(27)Al} TRAPDOR (transfer population in double
      resonance) NMR results, the (19)F resonances at -151 and -166 ppm are therefore
      assigned to (19)F spins associated with the fluorines in the terminal Al-F and
      the bridging Al-F-Al groups, respectively.

PMID- 17004756
TI  - Formation of regular surface-supported mesostructures with periodicity controlled
      by chemical reaction rate.
AB  - We report a LEEM and XPEEM study of the formation of a variety of stationary two
      dimensional metallic and oxygen structures in Au and Au + Pd adlayers on Rh(110)
      during water formation reaction. They result from chemically frozen spinodal
      decomposition and are created, preserved, or reversibly modified by tuning the
      reaction conditions. The wavelength of lamellar structures obtained at
      intermediate metal coverage is found to obey a power scaling law with respect to
      the reaction rate.

PMID- 17004757
TI  - X-ray photoemission for probing charging/discharging dynamics.
AB  - A novel technique is introduced for probing charging/discharging dynamics of
      dielectric materials in which X-ray photoemission data is recorded while the
      sample rod is subjected to +/-10.0 V square-wave pulses with varying frequencies
      in the range of 10(-3) to 10(3) Hz. For a clean silicon sample, the Si2p(Si(0))
      peak appears at correspondingly -10.0 eV and +10.0 eV binding energy positions
      (20.0 eV difference) with no frequency dependence. However, the corresponding
      peak of the oxide (Si(4+)) appears with less than 20.0 eV difference and exhibits
      a strong frequency dependence due to charging of the oxide layer, which is
      faithfully reproduced by a theoretical model. In the simplest application of this
      technique, we show that the two O1s components can be assigned to SiO(x) and
      TiO(y) moeties by correlating their dynamical shifts to those of the Si2p and
      Ti2p peaks in a composite sample. Our pulsing technique turns the powerful X-ray
      photoemission into an even more powerful impedance spectrometer with an added
      advantage of chemical resolution and specificity.

PMID- 17004758
TI  - Orbital interaction mechanisms of conductance enhancement and rectification by
      dithiocarboxylate anchoring group.
AB  - We study computationally the electron transport properties of dithiocarboxylate
      terminated molecular junctions. Transport properties are computed self
      consistently within density functional theory and nonequilibrium Green's
      functions formalism. A microscopic origin of the experimentally observed current
      amplification by dithiocarboxylate anchoring groups is established. For the 4,4'
      biphenyl bis(dithiocarboxylate) junction, we find that the interaction of the
      lowest unoccupied molecular orbital (LUMO) of the dithiocarboxylate anchoring
      group with LUMO and highest occupied molecular orbital (HOMO) of the biphenyl
      part results in bonding and antibonding resonances in the transmission spectrum
      in the vicinity of the electrode Fermi energy. A new microscopic mechanism of
      rectification is predicted based on the electronic structure of asymmetrical
      anchoring groups. We show that the peaks in the transmission spectra of 4'
      thiolato-biphenyl-4-dithiocarboxylate junction respond differently to the applied
      voltage. Depending upon the origin of a transmission resonance in the orbital
      interaction picture, its energy can be shifted along with the chemical potential
      of the electrode to which the molecule is more strongly or more weakly coupled.

PMID- 17004759
TI  - Mechanisms, pathways, and dynamics of excited-state energy flow in self-assembled
      wheel-and-spoke light-harvesting architectures.
AB  - Static and time-resolved optical measurements are reported for two cyclic
      hexameric porphyrin arrays and their self-assembled complexes with guest
      chromophores. The hexameric hosts contain zinc porphyrins and 0 or 3 free base
      (Fb) porphyrins (denoted Zn(6) or Zn(3)Fb(3), respectively). The guests are a
      tripyridyl arene (TP) and a dipyridyl-substituted free base porphyrin (DPFb),
      each of which coordinates to zinc porphyrins of a host via pyridyl-zinc dative
      bonding. Each architecture is designed to have an overall gradient of excited
      state energies that affords excitation funneling within the host and ultimately
      to the guest. Collectively, the studies delineate the various pathways,
      mechanisms, and rate constants of energy flow among the weakly coupled
      constituents of the host-guest complexes. The pathways include downhill
      unidirectional energy transfer between adjacent chromophores, bidirectional
      energy migration between identical chromophores, and energy transfer between
      nonadjacent chromophores. The energy transfer to the lowest-energy chromophore(s)
      within the backbone of a hexameric host (Fb porphyrins in Zn(3)Fb(3) or pyridyl
      coordinated zinc porphyrins in Zn(6)*TP and Zn(6)*DPFb) proceeds primarily via a
      through-bond mechanism; the transfer is rapid (approximately 40 ps depending on
      the array) and essentially quantitative (>or=98%). The energy transfer from a
      pyridyl-coordinated zinc porphyrin of the host to the Fb porphyrin guest in the
      Zn(6)*DPFb complex is almost exclusively Forster through-space in nature; this
      process is much slower ( approximately 1 ns) and has a lower yield (65%). These
      studies highlight the utility of cyclic architectures for efficient light
      harvesting and energy transfer to a designated trapping site.

PMID- 17004760
TI  - Effects of multiple pathways on excited-state energy flow in self-assembled wheel
      and-spoke light-harvesting architectures.
AB  - Static and time-resolved optical measurements are reported for three cyclic
      hexameric porphyrin arrays and their self-assembled complexes with guest
      chromophores. The hexameric hosts contain zinc porphyrins and 0, 1, or 2 free
      base (Fb) porphyrins (denoted Zn(6), Zn(5)Fb, or Zn(4)Fb(2), respectively). The
      guest is a core-modified (O replacing one of the four N atoms) dipyridyl
      substituted Fb porphyrin (DPFbO) that coordinates to zinc porphyrins of a host
      via pyridyl-zinc dative bonding. Each architecture is designed to have a gradient
      of excited-state energies for excitation funneling among the weakly coupled
      constituents of the host to the guest. Energy transfer to the lowest-energy
      chromophore(s) (coordinated zinc porphyrins or Fb porphyrins) within a hexameric
      host occurs primarily via a through-bond (TB) mechanism, is rapid ( approximately
      40 ps), and is essentially quantitative (>or=98%). Energy transfer from a pyridyl
      coordinated zinc porphyrin of the host to the guest in the Zn(6)*DPFbO complex
      has a yield of approximately 75%, a rate constant of approximately (0.7 ns)(-1),
      and significant Forster through-space (TS) character. In the case of
      Zn(5)Fb*DPFbO, which has an additional TS route via the Fb porphyrin with a rate
      constant of approximately (20 ns)(-1), the yield of energy transfer to the guest
      is somewhat lower ( approximately 50%) than that for Zn(6)*DPFbO. Complex
      Zn(4)Fb(2)*DPFbO has an identical TS pathway via the Fb porphyrin plus an
      additional TS pathway involving the second Fb porphyrin (closer to the guest)
      with a rate constant of approximately (0.5 ns)(-1). This complex exhibits an
      energy-transfer yield to the guest that is significantly enhanced over that for
      Zn(5)Fb*DPFbO and comparable to that for Zn(6)*DPFbO. Collectively, the results
      for the various arrays suggest designs for similar host-guest complexes that are
      expected to exhibit much more efficient light harvesting and excitation trapping
      at the central guest chromophore.

PMID- 17004761
TI  - Polymer-nanoparticle complexes: from dilute solution to solid state.
AB  - We report on the formation and the structural properties of "supermicellar"
      aggregates made from mineral nanoparticles and polyelectrolyte-neutral block
      copolymers in aqueous solutions. The mineral particles put under scrutiny are
      ultrafine and positively charged yttrium hydroxyacetate nanoparticles. Combining
      light, neutron, and X-ray scattering experiments, we have characterized the sizes
      and the aggregation numbers of the organic-inorganic complexes. We have found
      that the hybrid aggregates have typical sizes in the range of 100 nm and exhibit
      a remarkable colloidal stability with respect to ionic strength and concentration
      variations. Solid films with thicknesses up to several hundreds of micrometers
      were cast from solutions, resulting in a bulk polymer matrix in which
      nanoparticle clusters are dispersed and immobilized. It was found in addition
      that the structure of the complexes remains practically unchanged during film
      casting.

PMID- 17004762
TI  - Low-temperature growth of uniform ZnO particles with controllable ellipsoidal
      morphologies and characteristic luminescence patterns.
AB  - Uniform ellipsoidal ZnO particles have been synthesized in an aqueous solution in
      the presence of triethonalamine (TEA) mediated by sonication at the temperature
      below 80 degrees C. Scanning electron microscopy observations reveal that the
      ellipsoidal particles are highly uniform with a hexagonal cross-section. The
      morphologies of the ZnO particles can be systematically controlled from elongated
      rugby ball-like ellipsoidal to half-ellipsoidal by increasing the TEA
      concentration. Spatial resolved cathodoluminescence measurements at room
      temperature show that the ellipsoidal ZnO particles are intrinsically encoded
      with barcode-like ultraviolet luminescence patterns, which are of either a wide
      stripe or a narrow stripe perpendicular to the length at the core of the
      particles depending on the growth temperature. Moreover, the luminescence spectra
      of the ellipsoidal particles can be tuned by heat treatments at elevated
      temperatures, while maintaining the luminescence patterns. We believe that the
      well-defined uniform ellipsoidal ZnO particles embedded with unique luminescence
      characteristics hold great potential for use in bioengineering and photonics,
      such as biological labeling and optical probes.

PMID- 17004763
TI  - Solution and solid-state spectra of quinacridone derivatives as viewed from the
      intermolecular hydrogen bond.
AB  - Quinacridones are industrially important hydrogen-bonded pigments. The color in
      the solid state is vivid red, while it is pale yellow in solution, indicating
      evidently the involvement of intermolecular interactions in the solid state. The
      electronic structure has therefore been investigated with special attention to
      the role of intermolecular NH...O hydrogen bonds for three representative
      quinacridone compounds with different hydrogen-bond forming characteristics:
      unsubstituted gamma-quinacridone (gamma-QA) with two NH groups, mono-N
      methylquinacridone (MMQA) with one NH and one CH(3), and N,N'-dimethyl
      quinacridone (DMQA) with two CH(3) groups. The number of the NH...O hydrogen
      bonds per molecule is four, two, and zero for gamma-QA, MMQA, and DMQA,
      respectively. In solution, no significant difference in absorption maximum is
      recognized between gamma-QA, MMQA, and DMQA. However, in the solid state, the
      absorption maximum of gamma-QA appears at the longest wavelength, followed by
      MMQA and then DMQA, depending on the number of NH...O intermolecular hydrogen
      bonds. The role of the hydrogen bond is found to align transition dipoles in a
      "head-to-tail" fashion and to displace the absorption band toward longer
      wavelengths due to excitonic interactions. The extent of the spectral shift
      increases with increasing number of hydrogen bonds per molecule.

PMID- 17004764
TI  - Fabrication of nanorattles with passive shell.
AB  - This investigation describes the formation of a metal nanorattle with a pure
      metal shell by varying experimental parameters. The galvanic replacement reaction
      between silver and chloroauric acid was adopted to prepare hollow metal
      nanoparticles. This approach is extended to produce nanorattles of Au cores and
      Au shells by starting with Au(core)Ag(shell) nanoparticles as templates. The
      effect of temperature on the nanostructure of the final product is also
      considered. The composition of the shell in nanorattles can be controlled by
      varying the reaction temperature (to form pure gold or gold-silver alloy, for
      example). X-ray absorption fine structure spectroscopy is conducted to elucidate
      the fine structure of these nanoparticles. Partial alloying between the Au core
      and the Ag shell is observed by extended X-ray absorption fine structure (EXAFS).

PMID- 17004765
TI  - Disintegration mechanisms of charged aqueous nanodroplets studied by simulations
      and analytical models.
AB  - The mechanism of fragmentation processes in aqueous nanodroplets charged with
      ions is studied by molecular dynamics (MD) simulations. By using constant
      temperature MD, the evaporation of the water is naturally taken into account and
      sequences of ion fragmentation events are observed. The size of the critical
      radius of the charged droplet just before the fragmentation and the distribution
      of the sizes of the fragments are estimated. Comparison of the Rayleigh critical
      radius for fragmentation and simulation data is within 0.23 nm. This seemingly
      small difference arises from a large difference in the number of water molecules
      that makes fragmentation an activated process as in the ion evaporation mechanism
      (IEM). This finding is in agreement with the predictions of Labowsky et al.
      [Anal. Chim. Acta 2000, 406, 105-118] for charged aqueous drops. The size of the
      daughter droplets is larger than the prediction of Born's theory by 0.1 to 0.15
      nm. The nature and the dynamics of the intermediate states of the fragmentation
      process characterized by a bridge formed between the mother droplet and the
      evaporating ion or thorned structures where the ion sits on the tip are important
      for the outcome of the size-distribution of the fragments, while they are is
      missing in Born's theory.

PMID- 17004766
TI  - Hybrid materials covalently incorporated with isophorone-based dyes through sol
      gel process for nonlinear optical applications.
AB  - Two new push-pull type second-order nonlinear optical (NLO) active isophorone
      based alkoxysilane dyes with the same acceptor were synthesized and
      characterized. One silane (ICTES-HEMA) bears a chromophore with a hydroxyethyl
      methylamino donor and the other silane (ICTES-HMPP) is a bulkier analogue with a
      hydroxymethyl diphenylamino donor. Transparent, homogeneous films were prepared
      via the copolymerization of tetraalkoxysilane (TEOS) and different NLO silanes
      with the ratio of 5:1. The d(33) values obtained for the HEMA and HMPP films are
      46.3 and 20.6 pm/V, respectively. Normalized UV-vis spectra reveal that the
      introduction of a diaryl group would help to prevent unfavorable organization of
      the chromophores. The reorientation dynamic stabilities of the samples were
      studied by second-harmonic generation (SHG) measurements, demonstrating that
      bulkier chromophores incorporated in sol-gel materials would not necessarily lead
      to higher stabilities over time.

PMID- 17004767
TI  - Toward efficient photomodulation of conjugated polymer emission: optimizing
      differential energy transfer in azobenzene-substituted PPV derivatives.
AB  - We present fluorescence studies of quenching behavior in photoaddressable
      azobenzene-substituted derivatives of the fluorescent conjugated polymer poly(p
      phenylenevinylene) (PPV). The azobenzene side chains partially quench the PPV
      fluorescence, and we have shown previously that the quenching efficiency is
      greater when the azobenzene side chains are cis than when they are trans. This
      effect provides a photoaddressable means of modulating the fluorescence intensity
      of PPV derivatives. To optimize the efficiency of photoinduced intensity
      modulation, it is important to understand the molecular nature of quenching by
      both trans- and cis-azobenzene side chains. Here we investigate the photophysical
      origins of quenching by the two isomers using steady-state and time-resolved
      fluorescence spectroscopy. We present results from the azobenzene-modified PPV
      derivative poly(2-methoxy-5-((10-(4-(phenylazo)phenoxy)decyl)oxy)-1,4
      phenylenevinylene) (MPA-10-PPV) and two new related polymers, a copolymer lacking
      half of the azobenzene side chains and an analogue of MPA-10-PPV with a tert
      butyl-substituted azobenzene. These studies reveal that steric interactions
      influence the extent of PPV emission quenching by trans-azobenzene but do not
      affect the efficient quenching by cis-azobenzene. The difference in dynamic
      quenching efficiencies between trans- and cis-azobenzene isomers is consistent
      with fluorescence resonance energy transfer. These results show that it is
      possible to control the efficiency of photoswitchable fluorescence modulation
      through specific structural variations designed to encourage or block quenching
      by trans-azobenzene. This is a promising approach to providing useful general
      guidelines for designing photomodulated PPV derivatives.

PMID- 17004768
TI  - Influence of a TiCl4 post-treatment on nanocrystalline TiO2 films in dye
      sensitized solar cells.
AB  - In this study, the influence of the TiCl(4) post-treatment on nanocrystalline
      TiO(2) films as electrodes in dye-sensitized solar cells is investigated and
      compared to nontreated films. As a result of this post-treatment cell
      efficiencies are improved, due to higher photocurrents. On a microscopic scale
      TiO(2) particle growth on the order of 1 nm is observed. Despite a corresponding
      decrease of BET surface area, more dye is adsorbed onto the oxide surface.
      Although it seems trivial to match this finding with the improved photocurrent,
      this performance improvement cannot be attributed to higher dye adsorption only.
      This follows from comparison between incident photon to current conversion
      efficiency (IPCE) and light absorption characteristics. Since the charge
      transport properties of the TiO(2) films are already more than sufficient without
      treatment, the increase in short circuit current density J(SC) cannot be related
      to improvements in charge transport either. Transient photocurrent measurements
      indicate a shift in the conduction band edge of the TiO(2) upon TiCl(4)
      treatment. It is concluded that the main contribution to enhanced current
      originates from this shift in conduction band edge, resulting in improved charge
      injection into the TiO(2).

PMID- 17004769
TI  - Octopolar chromophores based on donor- and acceptor-substituted 1,3,5
      tris(phenylethynyl)benzenes: impact of meta-conjugation on the molecular and
      electronic structure by means of spectroscopy and theory.
AB  - The molecular and electronic structures of a series of all-meta-substituted
      phenylacetylene mesitylenes peripherally substituted with donor or acceptor (D-A)
      groups are studied. The impact of meta- and para-substitution patterns is also
      analyzed by employing Raman and optical spectroscopies in conjunction with
      theoretical calculations. Outer phenyl rings display a partial quinoid character
      induced by two different motifs: (i) outer phenyls --> triple bond charge
      transfer for the cases where these phenyls are substituted with electron-donors;
      (ii) double electron withdrawing effect in the molecules with the peripheral
      phenyls substituted with electron acceptors. A moderate tuning of the optical gap
      is observed in agreement with the partial blockade of pi-electron conjugation
      exerted by the meta disposition. The orbital structure of the compounds partially
      preserves that of the mesitylene group showing extra-conjugation due to the
      addition of the arms, so that conjugation is not entirely obstructed but
      partially impeded in the ground electronic state (i.e., electron occupied
      orbitals). As for the excited states, the low-lying energy empty orbitals offer
      better conditions for full conjugation over the whole molecular scaffold.
      Interesting optical properties such as overlapping centers along the lowest
      energy optical excitations and enhanced optical transparency with importance for
      the application of these materials in optoelectronics have been justified on the
      basis of the electronic structure. A greater degree of quinoidization, and more
      allowed pi-electron delocalization, over the entire molecule is recognized in the
      case of linear phenylacetylenes substituting in para positions the central core.

PMID- 17004770
TI  - Dynamics of benzene guest inside a self-assembled cylindrical capsule: a combined
      solid-state 2H NMR and molecular dynamics simulation study.
AB  - The reorientational dynamics of benzene-d(6) molecules hosted into the cavity of
      a cavitand-based, self-assembled capsule was investigated by Molecular Dynamics
      (MD) simulations and temperature-dependent solid-state (2)H NMR spectroscopy. MD
      simulations were preliminarily performed to assess the motional models of the
      guest molecules inside the capsules. An in-plane fast reorientation of the
      benzene guest around the C(6) symmetry axis (B1 motion), characterized by
      correlation times of the order of picoseconds, was predicted with an activation
      barrier ( approximately 8 kJ/mol) very similar to that found for neat benzene in
      the liquid state. An out-of-plane reorientation corresponding to a nutation of
      the C(6) symmetry axis in a cone angle of 39 degrees (B2 motion, 373 K) with an
      activation barrier ( approximately 39 kJ/mol) definitely larger than that of
      liquid benzene was also anticipated. In the temperature range 293-373 K
      correlation times of the order of a nanosecond have been calculated and a
      transition from fast to slow regime in the (2)H NMR scale has been predicted
      between 293 and 173 K. (2)H NMR spectroscopic analysis, carried out in the
      temperature range 173-373 K on the solid capsules containing the perdeuterated
      guest (two benzene molecules/capsule), confirmed the occurrence of the B1 and B2
      motions found in slow exchange in the (2)H NMR time scale. Line shape simulation
      of the (2)H NMR spectral lines permitted defining a cone angle value of 39
      degrees at 373 K and 35 degrees at 173 K for the nutation axis. The T(1) values
      measured for the (2)H nuclei of the encapsulated aromatic guest gave correlation
      times and energetic barrier for the in-plane motion B1 in fine agreement with
      theoretical calculation. The experimental correlation time for B2 as well as the
      corresponding energetic barrier are in the same range found for B1. A molecular
      mechanism for the encapsulated guest accounting for the B1 and B2 motions was
      also provided.

PMID- 17004771
TI  - High-resolution analysis of (Sc3C2)@ C80 metallofullerene by third generation
      synchrotron radiation X-ray powder diffraction.
AB  - The X-ray structure of Sc(3)C(82) is redetermined by the MEM/Rietveld method by
      using synchrotron radiation powder data at SPring-8, where the C(2) encapsulated
      structure available to discuss the Sc-Sc interatomic distances has been
      determined. The encapsulated three scandium atoms form a triangle shape. A
      spherical charge distribution originating from the C(2) molecule is located at
      the center of the triangle. Interatomic distances between Sc and Sc are 3.61(3) A
      in the triangle. The distance between Sc and the center of the C(2) molecule is
      2.07(1) A.

PMID- 17004772
TI  - Gold and silver nanoparticles in sensing and imaging: sensitivity of plasmon
      response to size, shape, and metal composition.
AB  - Plasmonic metal nanoparticles have great potential for chemical and biological
      sensor applications, due to their sensitive spectral response to the local
      environment of the nanoparticle surface and ease of monitoring the light signal
      due to their strong scattering or absorption. In this work, we investigated the
      dependence of the sensitivity of the surface plasmon resonance (frequency and
      bandwidth) response to changes in their surrounding environment and the relative
      contribution of optical scattering to the total extinction, on the size and shape
      of nanorods and the type of metal, that is, Au vs Ag. Theoretical consideration
      on the surface plasmon resonance condition revealed that the spectral
      sensitivity, defined as the relative shift in resonance wavelength with respect
      to the refractive index change of surrounding materials, has two controlling
      factors: first the bulk plasma wavelength, a property dependent on the metal
      type, and second on the aspect ratio of the nanorods which is a geometrical
      parameter. It is found that the sensitivity is linearly proportional to both
      these factors. To quantitatively examine the dependence of the spectral
      sensitivity on the nanorod metal composition and the aspect ratio, the discrete
      dipole approximation method was used for the calculation of optical spectra of Ag
      Au alloy metal nanorods as a function of Ag concentration. It is observed that
      the sensitivity does not depend on the type of the metal but depends largely on
      the aspect ratio of nanorods. The direct dependence of the sensitivity on the
      aspect ratio becomes more prominent as the size of nanorods becomes larger.
      However, the use of larger nanoparticles may induce an excessive broadening of
      the resonance spectrum due to an increase in the contribution of multipolar
      excitations. This restricts the sensing resolution. The insensitivity of the
      plasmon response to the metal composition is attributable to the fact that the
      bulk plasma frequency of the metal, which determines the spectral dispersion of
      the real dielectric function of metals and the surface plasmon resonance
      condition, has a similar value for the noble metals. On the other hand, nanorods
      with higher Ag concentration show a great enhancement in magnitude and sharpness
      of the plasmon resonance band, which gives better sensing resolution despite
      similar plasmon response. Furthermore, Ag nanorods have an additional advantage
      as better scatterers compared with Au nanorods of the same size.

PMID- 17004773
TI  - Toward the comparison of rare earth element and actinide behavior in materials: a
      computational study of Ce- and U-bearing britholites.
AB  - We present a computational investigation into the nature of bonds formed by f
      elements in materials. The paper presents an example of the incorporation of rare
      earth elements (REE) and actinides in minerals derived from fluorapatite:
      Ca(10)(PO(4))(6)F(2). These minerals, called britholites, allow many
      substitutions on all three Ca, P, and F sites and are considered as potential
      host phases for radioactive elements separated from nuclear waste. REE and
      actinides have very similar physical and chemical properties, but REE are not
      radioactive and much more easily handled. REE are, therefore, very often used as
      a surrogate for actinides in experimental studies. The representative elements of
      rare earths and actinides chosen for this first investigation are cerium and
      uranium, respectively. We have studied all the various configurations of
      Ca(9)X(PO(4))(6)(-)(y)()(SiO(4))(y)()F(2), where X stands for Ce(3+), Ce(4+),
      U(3+), and U(4+), and y is equal to 1 and 2 for three-time and four-time charged
      cations, respectively. Calculations have been performed within the density
      functional theory (DFT) framework according to the computation scheme determined
      in a previous study. The analysis of the energies of the various configurations
      shows that the incorporation of all the cations considered stabilizes the
      apatitic structure. This stabilization, however, is greater for four-time charged
      cations than for three-time charged ones, which shows that Ce and U are both
      preferentially substituted in the +IV oxidation state. In addition, the
      substitution in one of the two cationic sites of the apatitic structure is always
      more favorable. Then, the geometry analysis shows a larger decrease in size of
      this cationic site for U than for Ce, as well as different volume variations for
      Ce and U substitutions in the two cationic sites. This cannot be explained by
      steric effects alone. Finally, the electronic density analysis yields three
      essential results: U and Ce form significantly covalent bonds, U forms bonds more
      covalent than Ce, and finally four-time charged cations form more covalent bonds
      than three-time charged ones. The comparison of these results with the formation
      enthalpies of the various phases shows a positive correlation between the
      covalence degree of the bonds formed by the f-element and the stability of the
      structure. In addition, our results prove that Ce- and U-bearing britholites
      exhibit very similar energetic, structural, and electronic properties. Ce,
      therefore, appears to be a good simulant for U.

PMID- 17004774
TI  - Electrochemical observation of the photoinduced formation of alloyed ZnSe(S)
      nanocrystals.
AB  - Electrochemical studies of thiol-capped ZnSe nanocrystals in aqueous solution
      have demonstrated several distinct oxidation and reduction peaks in the
      voltammograms, with the peak positions being dependent on the size of the
      nanocrystals and their photoluminescence quantum efficiency. The evolution of the
      specific features in the cyclic voltammetric curves of ZnSe NCs as a function of
      their photochemical treatment is studied. The interpretation of the results based
      on the approaches previously developed for CdTe NCs is found to be in good
      correlation with the proposed mechanism of the ZnSe NCs phototreatment, i.e., the
      formation of a sulfur-enriched surface shell. By this, cyclic voltammetry has
      been demonstrated to be a powerful method for probing surface states of
      semiconductor NCs as well as for monitoring the evolution of these states during
      photochemical processing.

PMID- 17004775
TI  - Dithiocarbamate-capped silver nanoparticles.
AB  - Nanometer-sized silver particles were synthesized by using didecylamine
      dithiocarbamates as the protecting ligands. With control of the initial ligand
      metal feed ratios, the core diameter of the resulting particles was found to vary
      from about 5 to 2.5 nm, as determined by transmission electron microscopic
      measurements. The core size dispersity was also found to decrease with increasing
      feed ratio. In UV-visible spectroscopic studies, the particle surface plasmon
      resonance peak diminished in intensity as the particle core size decreased,
      whereas in electrochemical measurements, smaller sized particles gave rise to
      well-defined quantized charging voltammetric features, in contrast to the
      featureless responses with the larger particles. Such single electron-transfer
      behaviors were consistent with those observed in STM measurements involving
      individual nanoparticles. Overall, this study provides an effective approach to
      the synthesis of stable nanometer-sized silver nanoparticles with interesting
      electronic and electrochemical properties.

PMID- 17004776
TI  - Geometry dependent features of optically induced forces between silver
      nanoparticles.
AB  - A recently devised, discrete-dipole approximation (DDA) based method for
      computing optical forces is used to explore geometry dependent aspects of the
      light induced interactions between pairs of silver nanoparticles, including the
      influence of particle shape, relative positioning of the particles, and incident
      field orientation. The interactions are observed to have a large degree of
      generic character, independent of the details of the particle shape. The size of
      the optical forces is also compared to estimates for the van der Waals forces,
      and the results are used to assess the potential importance of radiation forces
      on recent experiments demonstrating photoinduced self-assembly of triangular
      silver nanoprisms.

PMID- 17004777
TI  - First-principles electronic structure study of the monoclinic crystal bismuth
      triborate BiB3O6.
AB  - Monoclinic BiB(3)O(6) is an excellent nonlinear optical material with many
      advantages compared to other borate crystals. The origins of the optical effects
      and the chemical stability of BiB(3)O(6) are studied with gradient-corrected
      hybrid B3PW density functional theory within the Gaussian-orbital-based CO-LCAO
      scheme. Including spin-orbit coupling, the B3PW hybrid functional provides an
      estimate of the indirect band gap of 4.29-4.99 eV closer to the experimental
      value of 4.3 eV than HF, LDA, or GGA. The crystal orbital overlap population to
      give a detailed first-principles analysis of chemical bonding and the density of
      optical absorptions by convoluting the occupied density of states and the virtual
      density of states have been calculated. Obvious Bi-O covalent bonds have been
      found with different energy ranges for 6s-2p and 6p-2p interactions. The reason
      that [BiO(4)](5-) units are mainly responsible for the optics of BiB(3)O(6) in
      the long-wavelength region is due to the electronic transfer from occupied O 2p
      to empty Bi 6p orbitals favored by the Bi-O covalent bonds. The relativistic and
      correlation effects lead to fundamental differences of the band structure,
      chemical bonds, and optical effects for BiB(3)O(6) compared with nonrelativistic
      and uncorrelated calculations.

PMID- 17004779
TI  - Nanoparticle size effects on methanol electrochemical oxidation on carbon
      supported platinum catalysts.
AB  - The particle size effect observed on the performance of Pt/C electrocatalysts
      toward the methanol oxidation reaction (MOR) has been investigated with
      differential electrochemical mass spectrometry (DEMS). The investigation has been
      conducted under both potentiodynamic and potentiostatic conditions as research on
      methanol electrochemical oxidation is closely related to interest in direct
      methanol fuel cells. The particle size effect observed on the MOR is commonly
      regarded as a reflection of different Pt-CO and Pt-OH bond strengths for
      different particle sizes. This work focuses mainly on the mechanism of methanol
      dehydrogenation on platinum which is central to the problem of the optimization
      of the efficiency of methanol electro-oxidation by favoring the CO(2) formation
      pathway. It was found that the partitioning of the methanol precursor among the
      end products on supported platinum nanoparticles is strongly dependent on
      particle size distribution. Also, it is postulated that the coupling among
      particles of different sizes via soluble products must be considered in order to
      understand the particle size effects on the observed trends of product formation.
      An optimum particle size range for efficiently electro-oxidizing methanol to
      CO(2) was found between 3 and 10 nm, and loss in efficiency is mostly related to
      the partial oxidation of methanol to formaldehyde on either too small or too
      large particles. The possible reasons for these observations are also discussed.

PMID- 17004778
TI  - Single lanthanide-doped oxide nanoparticles as donors in fluorescence resonance
      energy transfer experiments.
AB  - We used lanthanide-ion doped oxide nanoparticles, Y(0.6)Eu(0.4)VO(4), as donors
      in fluorescent resonance energy transfer (FRET) experiments. The choice of these
      nanoparticles allows us to combine the advantages of the lanthanide-ion emission,
      in particular the long lifetime and the large Stokes shift between absorption and
      emission, with the detectability of the nanoparticles at the single-particle
      level. Using cyanine 5 (Cy5) organic molecules as acceptors, we demonstrated FRET
      down to the single-nanoparticle level. We showed that, due to the long donor
      lifetime, unambiguous and precise FRET measurements can be performed in solution
      even in the presence of large free acceptor concentrations. Highly efficient
      energy transfer was obtained for a large number of acceptor molecules per donor
      nanoparticle. We determined FRET efficiencies as a function of Cy5 concentration
      which are in good agreement with a multiple acceptor-multiple donor calculation.
      On the basis of the donor emission recovery due to acceptor photobleaching, we
      demonstrated energy transfer from single-nanoparticle donors in fluorescence
      microscopy experiments.

PMID- 17004780
TI  - Factors governing the quality of aqueous CdTe nanocrystals: calculations and
      experiment.
AB  - The aqueous synthesis of thiol-stabilized semiconductor CdTe colloidal
      nanocrystals has been revisited. We found optimal conditions for the synthesis of
      high-quality CdTe NCs through a study of the influence of the initial conditions
      (structure and concentration of Cd-thiol complexes) on the quality of the CdTe
      nanocrystals. A numerical calculation shows a clear correlation between the
      concentration of CdL (where L is (SCH(2)COO)(2-)) in the initial solution and the
      photoluminescence quantum efficiency of the CdTe nanocrystals.

PMID- 17004781
TI  - Thermal decomposition of carbon precursors in decorated AFI zeolite crystals.
AB  - Mass spectrometry and thermogravimetric analysis are used to explore the thermal
      decomposition of carbon precursors (primarily the tripropylammonium cations)
      occluded within AlPO(4)-5 (AFI) crystals prepared in various media (in the
      presence or absence of F(-) ions, Si(4+) substations of P(5+)), with the aim to
      fabricate high-density 0.4-nm single-walled carbon nanotubes (SWNTs). It has been
      found that the tripropylammonium precursors exist in the as-synthesized crystals
      in three different forms: tripropylammonium fluoride, hydroxide, and
      tripropylammonium cation compensating for the negative charge of the framework.
      The latter is bonded to the framework by strong chemical interaction and its
      decomposition takes place by a series of beta-elimination reactions to give
      propylene and ammonia, with the stepwise formation of dipropylammonium and n
      propylammonium cations. The 0.4-nm SWNTs filling density was found to be higher
      than that resulting from the carbon precursor of tripropylammonium fluoride and
      hydroxide, because of the strong adsorption force of the channel walls to
      pyrolysate, as evidenced by the clear and strong radial breathing modes in Raman
      spectra.

PMID- 17004782
TI  - Direct synthesis of branched gold nanocrystals and their transformation into
      spherical nanoparticles.
AB  - We report a facile synthesis of branched gold nanocrystals by the addition of a
      suitable amount of NaOH to an aqueous solution of cetyltrimethylammonium bromide
      (CTAB), HAuCl(4), and ascorbic acid. The branched nanocrystals were formed within
      minutes of reaction and showed monopod, bipod, tripod, and tetrapod structures.
      They are crystalline and have smooth surfaces. These gold multipods are
      kinetically controlled products and are thermodynamically unstable. The branched
      nanocrystals quickly transformed into spherical nanoparticles within 1 h of
      reaction, and the process was essentially complete after 2 days. The
      morphological transformation has been monitored by both UV-vis absorption
      spectroscopy and electron microscopy. The appearance of two major absorption
      bands for the branched gold nanocrystals eventually became only a single band at
      529 nm for the spherical nanoparticles. The resulting nanoparticles are single
      crystals with diameters of 20-50 nm and do not show a faceted structure. When the
      freshly prepared branched nanocrystals are kept in a refrigerator at 4 degrees C,
      their multipod structure can be preserved for over a month without significant
      spectral shifts.

PMID- 17004783
TI  - Novel shape evolution of BaMoO4 microcrystals.
AB  - Dendritic BaMoO(4) microcrystals with lengths of about 5-15 microm were
      synthesized simply under ambient conditions by a microemulsion-mediated method
      within an ultrashort time. The products were characterized by X-ray powder
      diffraction (XRD), transmission electron microscopy (TEM), and field-emission
      scanning electron microscopy (FESEM), which showed that the products were in pure
      tetragonal BaMoO(4) structure and that an individual dendrite had a long central
      stem with four array shrunken branches. Detailed studies revealed that the
      formation of these 3-D structures was strongly dependent on the composition of
      the microemulsion. At prolonged aging time, the dendrites evolved into rods and
      further into particles, driven by the lattice distortion energy required to
      evolve the crystal from a metastable to a stable state. This novel crystal shape
      evolution provides insight into crystallization behavior given that the growth
      history and shape evolution process have traditionally been poorly understood.

PMID- 17004784
TI  - Transformation of hydrogel-based inverse opal photonic sensors from FCC to L1(1)
      during swelling.
AB  - The structural evolution of Bragg diffracting inverse opal hydrogel sensors
      during swelling is directly observed by two-photon laser scanning fluorescence
      microscopy and compared to predictions from finite element analysis. A
      fluorescently labeled pH-sensitive hydrogel is UV-polymerized in a dried
      polystyrene colloidal crystal template, which is etched to yield an inverse opal.
      Fluorescence imaging of the hydrogel at different pH values reveals an
      inhomogeneous deformation of the FCC array of aqueous pores. The pores elongate
      along the sample normal direction and collapse along the sample parallel
      directions, consistent with the Bragg response, which indicates a 1-D increase in
      the interlayer distance. Interconnects between the pores serve as anchor points
      during hydrogel expansion into the pores. Pinning of the hydrogel to the
      substrate causes a change of the hydrogel lattice symmetry during deformation,
      from FCC (ABC stacking) to L1(1) (ABCA'B'C' stacking). Reconstructed cross
      sections confirm that a 1-D increase in the interlayer distance along the
      substrate normal direction is responsible for the diffraction response of an
      inverse opal hydrogel sensor. Comparison with predictions from finite element
      analysis shows qualitative agreement, although the experimental mesostructure is
      significantly more deformed than the calculated data, due to buckling in the
      experimental system that is not captured by the model.

PMID- 17004785
TI  - Substitutional boron in nanodiamond, bucky-diamond, and nanocrystalline diamond
      grain boundaries.
AB  - Although boron has been known for many years to be a successful dopant in bulk
      diamond, efficient doping of nanocrystalline diamond with boron is still being
      developed. In general, the location, configuration, and bonding structure of
      boron in nanodiamond is still unknown, including the fundamental question of
      whether it is located within grains or grain boundaries of thin films and whether
      it is within the core or at the surface of nanoparticles. Presented here are
      density functional tight-binding simulations examining the configuration,
      potential energy surface, and electronic charge of substitutional boron in
      various types of nanocrystalline diamond. The results predict that boron is
      likely to be positioned at the surface of isolated particles and at the grain
      boundary of thin-film samples.

PMID- 17004787
TI  - Customized morphologies of self-condensed multisegment polymer nanowires.
AB  - The direct formation of multisegment nanowires consisting of polymer domains by
      ion beam irradiation is investigated. Cross-linking reactions in the ion tracks
      result in localized gelation, giving isolated nanowires on substrates. It is
      demonstrated that the morphology of the final nanostructure is customized by
      appropriate selection of the ion fluence, combination of polymers, and the
      solvent employed for development. Octopus-like nanostructures consisting of a
      tangled hydrophilic polymer core and splayed hydrophobic polymer segments are
      successfully produced as an example of the process. The present technique
      provides universal feasibility for the formation of nanostructures based on "any"
      polymer materials in which radiation induces cross-linking reactions.

PMID- 17004786
TI  - High-temperature seedless synthesis of gold nanorods.
AB  - We demonstrate seedless synthesis of gold nanorods at high temperatures up to 97
      degrees C. Using the correct silver nitrate concentration is crucial for
      formation of rod-shaped particles at all temperatures. We observed a decrease of
      nanorod length with increasing temperature, while the width stays constant
      throughout the temperature range. From kinetics studies, we show 3 orders of
      magnitude increase in nanorod growth rate when the temperature is raised from
      room temperature to 97 degrees C. From the temperature dependence of the growth
      rate, we obtain a average activation energy for growth on all facets of 90 +/- 10
      kJ mol(-1). High-temperature synthesis of gold nanorods presents a more
      attractive method for scalable flow-based production of gold nanorods.

PMID- 17004788
TI  - Core-shell microspherical Ti(1-x)Zr(x)O2 solid solution photocatalysts directly
      from ultrasonic spray pyrolysis.
AB  - A series of Ti(1-x)Zr(x)O(2) solid solutions photocatalysts (x = 0.000, 0.045,
      0.090, 0.135, and 0.180) was directly obtained by an ultrasonic spray pyrolysis
      method. Compared with previous methods for solid solutions, our preparation was
      very fast. The resulting samples were characterized by X-ray diffraction,
      scanning electron microscopy, transmission electron microscopy, high-resolution
      transmission electron microscopy, nitrogen adsorption, and UV-vis diffuse
      reflectance spectroscopy. The characterizations revealed core-shell spherical
      structures of the resulting solid solutions. We evaluated photocatalytic
      activities of the solid solutions on degradation of rhodamine B in aqueous
      solution under simulated solar light. It was found that Ti(0.91)Zr(0.09)O(2)
      solid solution exhibited the highest photocatalytic activity among all the as
      prepared samples. Its activity was much higher than that of P25. The formation
      mechanism of core-shell spherical structures was proposed. Moreover, we
      successfully extended this method to prepare microspheres of ceria and ceria
      zirconia solid solutions. We think this general method may be easily scaled up
      for industrial production of microspherical solid solutions photocatalysts and
      catalysts.

PMID- 17004789
TI  - Intramolecular charge transfer assisted by conformational changes in the excited
      state of fluorene-dibenzothiophene-S,S-dioxide co-oligomers.
AB  - The strong solvatochromism observed for two fluorene-dibenzothiophene-S,S-dioxide
      oligomers in polar solvents has been investigated using steady-state and time
      resolved fluorescence techniques. A low-energy absorption band, attributed to a
      charge-transfer (CT) state, is identified by its red shift with increasing
      solvent polarity. In nonpolar solvents, the emission of these conjugated
      luminescent oligomers shows narrow and well-resolved features, suggesting that
      the emission comes from a local excited state (LE), by analogy to their
      conjugated fluorene-based polymer counterparts. However, in polar solvents, only
      a featureless broad emission is observed at longer wavelengths (CT emission). A
      linear correlation between the energy maximum of the fluorescence emission and
      the solvent orientation polarizability factor Deltaf (Lippert-Mataga equation) is
      observed through a large range of solvents. In ethanol, below 230 K, the emission
      spectra of both oligomers show dual fluorescence (LE-like and CT) with the
      observation of a red-edge excitation effect. The stabilization of the CT emissive
      state by solvent polarity is accompanied/followed by structural changes to adapt
      the molecular structure to the new electronic density distribution. In ethanol,
      above 220 K, the solvent reorganization occurs on a faster time scale (less than
      10 ps at 290 K), and the structural relaxation of the molecule (CT(unrelaxed) -->
      CT(Relaxed)) can be followed independently. The magnitude of the forward rate
      constant, k(1)(20 degrees C) approximately 20 x 10(9) s(-1), and the reaction
      energy barrier, E(a) approximately 3.9 kcal mol(-1), close to the energy barrier
      for viscous flow in ethanol (3.54 kcal mol(-1)), show that large-amplitude
      molecular motions are present in the stabilization of the CT state.

PMID- 17004790
TI  - Vortices and their relation to ring currents and magnetic moments in
      nanographenes in high magnetic field.
AB  - Much attention has been paid to the role of vortices in the magnetic response
      properties of superconductors, but less so for molecular systems. Here we present
      a theoretical analysis on nanographenes subject to a strong homogeneous magnetic
      field. The analysis is based on the simple Huckel-London model, for which we
      derive the topological definition of vorticity. The results are confirmed by a
      more elaborate model that includes nonnearest neighbor interaction, the explicit
      presence of nuclei and all terms due to the magnetic field. We find that due to
      frontier orbital intersections, large changes in magnetic dipole moments occur.
      Orbital energy minima and maxima can be related to change of vortex patterns with
      flux.

PMID- 17004791
TI  - Kinetic aspects of ion exchange in KhFek[Fe(CN)6]l*mH2O compounds: a combined
      electrical and mass transfer functions approach.
AB  - The present paper quantifies and develops the kinetic aspects involved in the
      mechanism of interplay between electron and ions presented elsewhere(1) for
      K(h)Fe(k)[Fe(CN)(6)](l)*mH(2)O (Prussian Blue) host materials. Accordingly, there
      are three different electrochemical processes involved in the PB host materials:
      H(3)O(+), K(+), and H(+) insertion/extraction mechanisms which here were fully
      kinetically studied by means of the use of combined electronic and mass transfer
      functions as a tool to separate all the processes. The use of combined electronic
      and mass transfer functions was very important to validate and confirm the
      proposed mechanism. This mechanism allows the electrochemical and chemical
      processes involved in the K(h)Fe(k)[Fe(CN)(6)](l)*mH(2)O host and Prussian Blue
      derivatives to be understood. In addition, a formalism was also developed to
      consider superficial oxygen reduction. From the analysis of the kinetic processes
      involved in the model, it was possible to demonstrate that the processes
      associated with K(+) and H(+) exchanges are reversible whereas the H(3)O(+)
      insertion process was shown not to present a reversible pattern. This
      irreversible pattern is very peculiar and was shown to be related to the
      catalytic proton reduction reaction. Furthermore, from the model, it was possible
      to calculate the number density of available sites for each
      intercalation/deintercalation processes and infer that they are very similar for
      K(+) and H(+). Hence, the high prominence of the K(+) exchange observed in the
      voltammetric responses has a kinetic origin and is not related to the amount of
      sites available for intercalation/deintercalation of the ions.

PMID- 17004792
TI  - Thermodynamic aspects of ion intercalation in KhFek[Fe(CN)6]l*mH2O compounds:
      application to the Everit's Salt/Prussian blue transition.
AB  - The K(+) reversible processes for ion exchange in K(h)Fe(k)[Fe(CN)(6)](l)*mH(2)O
      host compounds (Prussian Blue) were thermodynamically analyzed. A thermodynamic
      approach was established and developed based on the consideration of a lattice
      gas model where the electronic contribution to the chemical potential is
      neglected and the ion-host interaction is not considered. The occupation fraction
      of the intercalation process was calculated from the kinetic parameters obtained
      through ac-electrogravimetry in a previous paper. In this way, the mass potential
      transfer function introduces a new way to evaluate the thermodynamic aspect of
      intercalation. Finally, based on the thermodynamic approach, the energy used to
      put each K(+) ion into the host material was calculated. The values were shown to
      be in good agreement with the values obtained through transient techniques, for
      example, cyclic voltammetry. As a result, this agreement between theory and
      experimental data validates the thermodynamic approach considered here, and for
      the first time, the thermodynamic aspects of insertion were considered for mixed
      valence materials.

PMID- 17004793
TI  - Bundling and diameter selectivity in HiPco SWNTs poly(p-phenylene vinylene-co-2,5
      dioctyloxy-m-phenylene vinylene) composites.
AB  - Temperature-dependent (TD) Raman measurements at laser excitation 514.5 nm were
      performed at different concentrations. The spectral profile of the radial
      breathing modes were investigated up to a polymer concentration of 1 g/L and were
      found to be dominated by approximately 1.2-1.4 nm diameter tubes at room
      temperature. Upon heating above the glass transition of the polymer (60 degrees
      C) the smaller tubes around approximately 0.9 nm increased significantly in
      relative intensity. This suggests that below the glass transition of the polymer
      (60 degrees C) RBMs within the composite are damped and spectral changes cannot
      be interpreted as diameter selective solubilization. The observed RBM damping at
      room temperature only occurred up to a concentration of approximately 1.2 x 10(
      4) g/L and below this no damping was observed. Photoluminescence intensity (PL)
      measurements were taken for a range of PmPV concentrations, in which HiPco single
      walled carbon nanotubes (SWNTs) at 100%, 10%, 1%, 0.1%, 0.01%, and 0% mass
      fractions were added. Fitting of the concentration dependence to a dynamic
      absorption/desorption model indicates that the polymer interacts with nanotube
      bundles until a critical concentration of approximately 1.2 x 10(-4) g/L is
      reached, below which the nanotubes are isolated. The polymer and or solvent has a
      significant effect on the debundling and aggregation within these systems.
      Aggregation and/or interaction with the polymer at higher concentrations can
      effect the RBM profile in the composite at ambient temperatures, providing an
      incomplete representation of the selection of diameters present within composites
      at a particular wavelength.

PMID- 17004794
TI  - Grazing incidence X-ray scattering to probe the self-assembly of phthalocyanine
      nanorods on a liquid surface.
AB  - The structural properties of Langmuir monolayers on aqueous substrates of a metal
      free phthalocyanine, 2,9,16,23-tetrakis(phenylthio)-29H,31H-phthalocyanine and an
      Aluminum centered phthalocyanine, Aluminum 2,9,16,23-tetrakis(phenylthio)-29H,31H
      phthalocyanine chloride are reported here. Their structure is investigated under
      progressive lateral compression by grazing incidence diffuse X-ray scattering out
      of the specular plane to determine specular reflectivity-like information where
      the phase change of the molecules from "flat-lying" on the surface to "edge
      standing" perpendicular to the surface was directly observed. Furthermore grazing
      incident X-ray diffraction is used to investigate the in-plane ordering of the
      system where it has been found that at high density states the systems can be
      considered as monolayers consisting of arrays of side-by-side cofacially
      aggregated cylindrical rodlike entities.

PMID- 17004795
TI  - Interaction of hydrogen with cerium oxide surfaces: a quantum mechanical
      computational study.
AB  - The interaction of the (110) and (111) surfaces of ceria (CeO(2)) with atomic
      hydrogen is studied with ab initio calculations based on density functional
      theory. A Hubbard U term added to the standard density functional allows to
      accurately describe the electronic structure of the two surfaces. The minimum
      energy configuration for the adsorbed H on each of the two surfaces is obtained.
      An O-H-O bridge is formed on the (110) surface, whereas an axial tricoordinated
      OH group results on the (111) surface. For both surfaces, the adsorption of an H
      atom is accompanied by the reduction of a single Ce ion (which is one of the
      nearest neighbors of the adsorbed atom) and by a substantial outward protrusion
      of the O atom(s) directly bound to H. The adsorption of atomic H on the (110) and
      (111) surfaces is energetically favored by -150.8 and -128.3 kJ/mol,
      respectively, with respect to free molecular H(2). The calculated frequencies for
      the OH stretching vibrational mode are 3100 cm(-1) for the (110) surface and 3627
      cm(-1) for the (111) surface. The latter value is in excellent agreement with
      experimental data reported in the literature.

PMID- 17004796
TI  - Determination of electron transfer kinetic parameters by fourier transform
      electrochemical impedance spectroscopic analysis.
AB  - A new attempt to obtain electron transfer kinetic parameters at an electrified
      electrode/electrolyte interface using Fourier transform electrochemical impedance
      spectroscopic (FTEIS) analyses of small potential step chronoamperometric
      currents is presented. The kinetic parameters thus obtained allowed mass
      transport free voltammograms to be constructed in an overpotential region, where
      the diffusion limits the electron transfer reaction, using the Butler-Volmer (B
      V) relation. The B-V voltammograms clearly distinguish electrode reactions that
      are not much different in their electron transfer kinetic parameters, thus
      showing very similar normal linear sweep voltammetric (SCV) behaviors.
      Electrochemical reduction of p-benzoquinone, which displays nearly the same SCV
      responses at a gold electrode regardless whether the electrode is covered by a
      thiolated beta-cyclodextrin self-assembled monolayer, was taken as an example for
      the demonstration. The results show that the two voltametrically similar systems
      display very different electron transfer characteristics.

PMID- 17004797
TI  - Determination of the interfacial characteristics of a series of bolaamphiphilic
      poly(fluorooxetane) surfactants through molecular dynamics simulation.
AB  - Constant surface tension (NgammaT) and constant volume (NVT) molecular dynamics
      simulations have been conducted on a series of bolaamphiphilic alpha,varpi
      (diammonium disulfato)poly(fluorooxetane)s and on a typical "long-chain" anionic
      fluorosurfactant used to improve the flow-and-leveling characteristics of aqueous
      coatings, to compare their behavior at a water/air interface. Recent research has
      shown that the poly(fluorooxetane) surfactants considered in this paper could
      serve as an effective substitute for traditional fluorosurfactants used in flow
      and-leveling applications.(1) From molecular dynamics simulation, we have
      determined the saturated interfacial area per surfactant, interfacial area per
      surfactant as a function of surface tension, density profiles, the degree of
      hydration for various atoms in each surfactant, the degree of counterion binding,
      and order parameters. Our results for saturated interfacial area per surfactant
      molecule are greater than what has been obtained by other researchers through
      parametric fitting of interfacial area from experimental surface tension data
      using the Davies isotherm. Possible explanations for this difference are
      discussed. The low interfacial areas occupied by each poly(fluorooxetane) at the
      water/air interface are the result of their ability to adopt a "looped"
      conformation, in which the carbon and oxygen backbone of each surfactant and the
      attached perfluoroalkyl chains are forced into the air phase. A geometrically
      defined penetration parameter was calculated from the density profiles, which
      reveals that each poly(fluorooxetane) surfactant is more effective at separating
      the air and water phases than the "long-chain" anionic fluorosurfactant. The
      degree of hydration measured for different atoms in poly(fluorooxetane) during
      simulation confirms that a "looped" conformation is adopted in which the
      surfactant backbone and the perfluoroalkyl chains are lifted away from the water
      surface. Calculation of order parameters revealed a much lower degree of ordering
      for the perfluoroalkyl side chains in each bolaamphiphile than in the "long
      chain" anionic fluorosurfactant. When viewed in the context of the penetration
      parameter analysis, the density profiles and hydration data suggest why each
      poly(fluorooxetane) is capable of significantly reducing surface tension when
      other fluorosurfactants with similarly short perfluoroalkyl moieties provide
      inadequate surface tension reduction for practical flow-and-leveling
      applications.

PMID- 17004798
TI  - Effect of energy disorder in interfacial kinetics of dye-sensitized solar cells
      with organic hole transport material.
AB  - We describe the kinetic rates for dye regeneration in dye-sensitized solar cells
      with organic solid hole conductors, taking as a reference the experimental
      results of Haque et al. (ChemPhysChem 2003, 4, 89). Our model is based on Marcus
      rates for electron and hole transfer, emphasizing the Gaussian spread of energy
      levels in the molecular materials involved. We show that the energy disorder
      implies a broadening of the efficiency of hole transfer with respect to the
      thermodynamic driving force, as observed experimentally. The model also shows
      that tunning of the kinetic processes for high efficiency of energy conversion of
      the solar cell depends critically on the interplay between the reorganization
      energy and the broadening parameters of the energy distributions.

PMID- 17004799
TI  - Molecular assembled self-doped polyaniline interlayer for application in polymer
      light-emitting diode.
AB  - Self-doped polyaniline (SPANI) ultrathin films were prepared by using a self
      assembly process consisting of a self-doping monomer (o-aminobenzenesulfonic
      acid, SAN) and aniline (AN). SAN-AN copolymerization and film formation were
      simultaneously performed in aqueous solution. An immersing self-assembly method
      was developed to build up a SPANI nanofilm on an ITO glass, providing a hole
      injection layer in a double-layer electroluminescence (EL) device ITO/SPANI
      nanofilm//MEH-PV//Ca/Al. This device produces an orange EL as compared with a
      single-layer EL device of ITO//MEH-PV//Ca/Al. A double-layer device demonstrates
      that a SPANI film is capable of transporting holes in a polymer light-emitting
      diode (PLED).

PMID- 17004800
TI  - Water-gas-shift reaction on molybdenum carbide surfaces: essential role of the
      oxycarbide.
AB  - Density functional theory (DFT) was employed to investigate the behavior of Mo
      carbides in the water-gas-shift reaction (WGS, CO + H(2)O --> H(2) +CO(2)). The
      kinetics of the WGS reaction was studied on the surfaces of Mo-terminated
      Mo(2)C(001) (Mo-Mo(2)C), C-terminated Mo(2)C(001) (C-Mo(2)C), and Cu(111) as a
      known active catalyst. Our results show that the WGS activity decreases in a
      sequence: Cu > C-Mo(2)C > Mo-Mo(2)C. The slow kinetics on C-Mo(2)C and Mo-Mo(2)C
      is due to the fact that the C or Mo sites bond oxygen too strongly to allow the
      facile removal of this species. In fact, due to the strong O-Mo and O-C
      interactions, the carbide surfaces are likely to be covered by O produced from
      the H(2)O dissociation. It is shown that the O-covered Mo-terminated Mo(2)C(001)
      (O_Mo-Mo(2)C) surface displays the lowest WGS activity of all. With the Mo oxide
      in the surface, O_Mo-Mo(2)C is too inert to adsorb CO or to dissociate H(2)O. In
      contrast, the same amount of O on the C-Mo(2)C surface (O_C-Mo(2)C) does not lead
      to deactivation, but enhances the rate of the WGS reaction and makes this system
      even more active than Cu. The good behavior of O_C-Mo(2)C is attributed to the
      formation of a Mo oxycarbide in the surface. The C atoms destabilize O-poisoning
      by forming CO species, which shift away from the Mo hollow sites when the surface
      reacts with other adsorbates. In this way, the Mo sites are able to provide a
      moderate bond to the reaction intermediates. In addition, both C and O atoms are
      not spectators and directly participate in the WGS reaction.

PMID- 17004802
TI  - A comparison between interfacial electron-transfer rate constants at metallic and
      graphite electrodes.
AB  - The Fermi golden rule formalism has been used to derive the rate constant for
      interfacial electron transfer from a semimetallic electrode, such as highly
      ordered pyrolytic graphite (HOPG), to a redox couple in solution. A simple
      expression is presented that semiquantitatively relates the electron-transfer
      rate constant at a semimetallic electrode to that at a metallic electrode. The
      approach allows for the estimation of the value of the rate constant for
      interfacial charge transfer to nonadsorbing outer-sphere redox species at
      semimetallic electrodes. Rate constants for interfacial electron transfer for a
      variety of one-electron redox couples at semimetallic electrodes have been
      calculated relative to the rate constant of the ferrocenium/ferrocene redox
      couple at a gold electrode. Good agreement is found, in general, between the
      calculated and observed rate constants.

PMID- 17004801
TI  - Investigation of electro-oxidation of methanol and benzyl alcohol at boron-doped
      diamond electrode: evidence for the mechanism for fouling film formation.
AB  - Boron-doped diamond (BDD) and glassy carbon (GC) electrodes are compared for
      electrochemical oxidation of methanol and benzyl alcohol. Cyclic voltammograms
      reveal that BDD electrode produces good oxidation signals for both methanol and
      benzyl alcohol, while GC produces no significant oxidation signal for either
      methanol or benzyl alcohol. Amperometric measurement of oxidation of methanol and
      benzyl alcohol on BDD shows development of a fouling film for benzyl alcohol but
      not for methanol. Prolonged (24 h) polarization of the BDD electrode at +2.0 V in
      benzyl alcohol generated enough fouling film for investigation by AFM, SEM,
      Raman, and FTIR techniques. AFM and SEM microscopy images confirm a fouling film
      confined to the low-lying regions of the polycrystallite BDD surface, indicating
      that the active sites of benzyl alcohol oxidation are located within these low
      lying regions. The fouling material generated in the process of benzyl alcohol
      oxidation was identified from Raman and FTIR spectroscopy as polyester.
      Experiments confirm the fouling film can be removed and the electrode surface
      reactivated by brief polarization at +3.0 V. Amperometric results of
      concentration dependence confirm the BDD electrode is well suited for
      quantitative analysis applications of methanol and benzyl alcohol, with
      recognizable oxidation currents at micromolar concentration levels.

PMID- 17004803
TI  - Relationship between the growth regime of polyelectrolyte multilayers and the
      polyanion/polycation complexation enthalpy.
AB  - The alternate deposition of polyanions and polycations leads to the formation of
      films called polyelectrolyte multilayer films (PEMs). Two types of growth
      processes are reported in the literature, leading to films that grow either
      linearly or exponentially with the number of deposition steps. In this article we
      try to establish a correlation between the nature of the growth process and the
      heat of complexation between the polyanions and the polycations constituting the
      PEM film. Isothermal titration microcalorimetry experiments performed on several
      polyanion/polycation systems seem to indicate that an endothermic complexation
      process is characteristic of an exponential film growth, whereas a strongly
      exothermic process corresponds to a linear growth regime. Finally, weakly
      exothermic processes seem to be associated with weakly exponentially growing
      films. These results thus show that exponentially growing processes are mainly
      driven by entropy. This explains why the exponential growth processes are more
      sensitive to temperature than the linear growing processes. This temperature
      sensitivity is shown on the poly-L-glutamic acid/poly(allylamine) system which
      grows either linearly or exponentially depending on the ionic strength of the
      polyelectrolyte solutions.

PMID- 17004805
TI  - Self-assembled colloidal crystals from ZrO2 nanoparticles.
AB  - Ordered three-dimensional (3-D) assemblies of nanocrystalline zirconia were
      synthesized from aqueous suspensions of ZrO(2) nanoparticles without the need for
      hydrocarbon surfactants or solvents to control colloidal crystal growth.
      Nanoparticles were suspended in mild acid and subsequently titrated from low to
      neutral pH. The solubility was reduced as the surfaces were neutralized,
      promoting assembly of the nanoparticles into ordered monoliths. TEM measurements
      indicated the formation of three-dimensional, hexagonal faceted, micrometer-sized
      colloidal crystals composed of 4 nm diameter ZrO(2) nanoparticles. Lacking
      organic surfactants, the colloidal crystals were exceptionally robust and were
      sintered at high temperatures (300-500 degrees C) for further stability. Small
      angle X-ray scattering (SAXS) measurements demonstrate that the samples become
      progressively more amorphous above 350 degrees C, although some ordered domains
      of nanoparticles persist. Additionally, the heat treatment dramatically increases
      the surface area of the colloidal crystals as water and residual organics are
      desorbed, revealing highly controlled interstitial spaces and pores.

PMID- 17004804
TI  - Gramicidin A channel in a matrix from a semifluorinated surfactant monolayer.
AB  - Gramicidin A, a polypeptide antibiotic forming transmembrane ion channels, has
      been incorporated into a Langmuir monolayer formed by a semifluorinated alkane
      (SFA). In this work, partially fluorinated tetracosane, perfluorohexyloctadecane
      (F6H18), has been applied, aiming at finding a suitable matrix for gramicidin A
      to be transferred onto solid support for a biosensor design. For this purpose,
      the physiological conditions were of special interest (mixed monolayers
      containing low gramicidin proportion and the surface pressure of 30 mN/m). Mixed
      monolayers of gramicidin and SFA were found to be miscible within the whole range
      of mole fractions. A very significant increase of the stability of SFA monolayer
      has been found in the presence of gramicidin, even at such a low proportion as
      X(gramicidin) = 0.1, which is reflected in a 3.5-fold increase of the collapse
      pressure value of mixed monolayer as compared to the film from pure SFA. This
      interesting phenomenon has been interpreted as being due to the existence of a
      strong dipole-dipole interaction between both film-forming molecules. Opposite
      sign of the measured electric surface potential for gramicidin and SFA, resulting
      from different directions of the dipole moment vectors in both film molecules,
      implies that the ordered, antiparallel orientation of the dipole moments in the
      mixed gramicidin/SFA system can be responsible for its extremely high stability.

PMID- 17004807
TI  - On the experimental estimation of surface enhanced raman scattering (SERS) cross
      sections by vibrational pumping.
AB  - We present an in-depth analysis of the experimental estimation of cross-sections
      in surface enhanced raman scattering (SERS) by vibrational pumping. The paper
      highlights the advantages and disadvantages of the technique, pinpoints the main
      aspects and limitations, and provides the underlying physical concepts to
      interpret the experimental results. Examples for several commonly used SERS
      probes are given, and a discussion on future possible developments is also
      presented. Obtaining good estimates of SERS cross-sections is, in general, an
      extremely hard problem and has been a longstanding ambition of the SERS community
      for reasons that go from the purely applied (quantification of signals) to the
      more fundamental (comparisons of theoretical electromagnetic enhancement factors
      with experiment). Any method that can produce a standard protocol for the
      estimation of cross-sections is, accordingly, of great interest and an effort to
      understand its principles and limitations is required.

PMID- 17004806
TI  - Hemoglobin adsorption to silica monitored with polarization-dependent evanescent
      wave cavity ring-down spectroscopy.
AB  - Evanescent-wave cavity ring-down spectroscopy was used to monitor the adsorption
      of human hemoglobin to a fused-silica surface from aqueous solution. An uncoated
      dove prism was situated in a ring-down cavity such that the beam entered and
      exited with a normal-incidence geometry. This afforded ring-down times as high as
      5 mus and values of sigma(tau)/tau as low as 0.3%. Normal-incidence geometry
      permits the detection of both S- and P-polarized light, yielding some information
      of the orientation of adsorbates. The orientation of the adsorbed hemoglobin
      molecules is found to change as adsorption progresses, but with a different time
      profile than adsorption itself. The adsorption kinetics from a quiescent solution
      is consistent with a reaction-diffusion model that includes both reversible and
      irreversible adsorption operating in parallel. Systems behaving according to this
      model also seem to display adsorption isotherms, although the increased
      adsorption from more concentrated solutions is only a consequence of the system
      being under kinetic control. In some cases, this may be sufficient to explain the
      paradox of protein adsorption systems which seem to be both irreversible and
      consistent with isotherm models as well.

PMID- 17004808
TI  - Controllable organization of a carboxylic acid type gemini surfactant at
      different pH values by adding Copper(II) ions.
AB  - The gemini surfactant sodium 4,8-dioctyl-3,9-dioxo-6-hydroxy-4,8-diaza-1,11
      undecanedicarboxylate (SDUC), bearing two carboxylic headgroups and two
      hydrocarbon chains, has been synthesized, and its self-organization
      characteristics at strong basic and neutral environments have been studied. The
      results reveal that a transition from micelles to vesicles in SDUC aqueous
      solution occurs when the pH drops from 12.0 to 7.0. When a small amount of Cu(2+)
      ion is added to the SDUC solutions at both pH 12.0 and 7.0, remarkable
      transformations were observed within the SDUC aggregate structures. At pH 12.0,
      micelles transform into vesicles as Cu(2+) is added, while the vesicles of SDUC
      are formed at pH 7.0 and these small vesicles tend to fuse into larger ones
      slowly. Moreover, these SDUC vesicles at pH 7.0 undergo a relatively fast fission
      process when Cu(2+) is added in. An attempt has been made to explain the
      mechanism of these transformations.

PMID- 17004810
TI  - The role of O2 in SERS-active thin metal film photodynamics.
AB  - Optical emission from thin Ag films excited by visible light under a non-oxygen
      atmosphere was analyzed as a function of time and excitation power. The emission
      behavior under anaerobic conditions was strikingly different from that obtained
      under an oxygen-containing atmosphere. Specifically, emission intensity increased
      as a function of time with no photoinduced signal decay. A simple mechanistic
      model was developed and demonstrated to accurately predict the photodynamic
      trends observed under both conditions. The model involves oxygen-mediated cyclic
      production and destruction of photoactive silver clusters on the thin film. The
      evidence presented here strongly supports the hypothesis that oxygen plays a key
      role in the "blinking" phenomenon observed on SERS-active Ag films.

PMID- 17004809
TI  - Competition between atmospherically relevant fatty acid monolayers at the
      air/water interface.
AB  - Competition and oxidation of fatty acids spread at the air/water interface were
      investigated using surface-specific, broad-bandwidth, sum frequency generation
      spectroscopy. At the air/water interface, a monolayer of oleic acid replaced a
      monolayer of deuterated palmitic acid at equilibrium spreading pressure.
      Subsequent oxidation of the oleic acid monolayer with ozone resulted in products
      more water soluble than the palmitic acid; therefore, the palmitic acid monolayer
      reformed at the surface. Results indicate that the surfactants on the surface of
      fat-coated tropospheric aerosols will only possess oxidized acyl chains after all
      less soluble species in the aqueous subphase have been removed through the
      processes of replacement at the surface and atmospheric oxidation.

PMID- 17004811
TI  - Comparing an ionic liquid to a molecular solvent in the cesium cation extraction
      by a calixarene: a molecular dynamics study of the aqueous interfaces.
AB  - We report a molecular dynamics (MD) study of the interfacial behavior of key
      partners involved in the Cs(+) cation extraction by a calix[4]arene-crown-6 host
      (L), comparing an ionic liquid (IL) to a classical molecular solvent (chloroform)
      as receiving "oil" phase. The IL is composed of hydrophobic 1-butyl-3
      methylimidazolium cations (BMI(+)) and bis(trifluoromethylsulfonyl)imide anions
      (Tf(2)N(-)) and forms a biphasic system with water. The simulations reveal
      similarities but also interesting differences between the two types of
      interfaces. Much longer times are needed to "equilibrate" IL systems, compared to
      classical liquid mixtures, and there is more intersolvent mixing with the IL than
      with chloroform, especially concerning the water-in-oil content. There is also
      some excess of the BMI(+) cations over the Tf(2)N(-) anions in the aqueous phase.
      Simulations on the Na(+)NO(3)(-) and Cs(+)NO(3)(-) ions show that they sometimes
      interact at the interface with the IL ions, forming hydrated intimate ion pairs,
      whereas they are "repelled" by the classical interface. The LCs(+) complex and L
      ligand also behave differently, depending on the "oil phase". They are better
      solvated by the IL than by chloroform and thus poorly attracted at the IL
      interface, whereas they adsorb at the chloroform interface, adopting well-defined
      amphiphilic orientations. The results are discussed in the context of assisted
      ion transfer and provide a number of arguments explaining the specificity and
      efficiency of IL based, compared to classical extraction systems.

PMID- 17004812
TI  - The origin of surface stress induced by adsorption of iodine on gold.
AB  - The cantilever technique for the measurement of film stress on both macroscopic
      and microscopic cantilevers is validated, then applied to the experimental
      determination of film stress induced by the adsorption of a monolayer of iodine
      onto a gold substrate. A model is proposed that relates the change in the
      interatom potential upon chemisorption of iodine onto gold to the measured film
      stress. Excellent agreement is found with the experimentally determined value.
      This result gives insight into the origins of film stress that is observed in all
      thin film and coating applications.

PMID- 17004813
TI  - Kinetics of photoinduced electron transfer in polythiophene-porphyrin-fullerene
      molecular films.
AB  - Photoinduced electron transfer (ET) processes were studied by the time-resolved
      Maxwell displacement charge (TRMDC) method in bilayer structures consisting of an
      electron donor-acceptor and conductive polymer monolayers, porphyrin-fullerene
      dyad and polyhexylthiophene, respectively, both layers prepared by the Langmuir
      Blodgett (LB) method. The charge separation involves two fast steps: an
      intramolecular ET in the dyad molecule followed by an interlayer ET from the
      polymer to the formed porphyrin radical cation. These fast vertical intra- and
      interlayer processes could not be time-resolved by the TRMDC method. The lifetime
      of the charge separated state in the system was extended to hundreds of
      milliseconds by lateral electron and hole transfers in fullerene and polymer
      sublayers. The kinetics of the system was described by a model involving two long
      living energetically different complete charge separated states. The data
      analysis indicates that the charge separation has a recombination time of 0.5 s.
      This is a promising result for possible applications.

PMID- 17004814
TI  - Spontaneous attachment of amines to carbon and metallic surfaces.
AB  - Primary alkylamines attach spontaneously from acetonitrile (ACN) solutions onto
      glassy carbon and metallic surfaces (Au, Pt, Cu, and Fe). The surface
      concentration of the organic layer measured from the integration of cyclic
      voltammograms appears close to or lower than that of a compact monolayer. The
      rate of the attachment depends on the concentration of the primary amino
      compound; it reaches a maximum after 3 h of immersion for the most concentrated
      solutions (20 mM). The modified surfaces have been characterized by cyclic
      voltammetry (CV), energy dispersive X-ray spectrometry (EDX), X-ray photoelectron
      spectroscopy (XPS), and infrared spectroscopy (ATR). The possible reaction
      mechanisms are discussed.

PMID- 17004815
TI  - Remarkable effect of the preparation technique on the state of cobalt ions in BEA
      zeolites evidenced by FTIR spectroscopy of adsorbed CO and NO, TPR and XRD.
AB  - The state of cobalt in two BEA zeolites was studied by XRD, TPR, and FTIR
      spectroscopy using CO and NO as probe molecules. One of the samples, CoAlBEA (0.4
      wt % of Co), was prepared by conventional ion exchange and the other, CoSiBEA
      (0.7 wt % Co), by a two-step postsynthesis method involving dealuminated SiBEA
      zeolite. The introduction of Co into SiBEA leads to an increase of unit cell
      parameters of the BEA structure and to the consumption of silanol groups in
      vacant T-sites of the dealuminated zeolite. In contrast, no structural changes
      are observed after incorporation of cobalt into AlBEA by ion-exchange. The
      reduction temperature of cobalt in CoSiBEA zeolite (1130 K), is much higher than
      for CoAlBEA and indicates a strong interaction of cobalt ions with SiBEA. Low
      temperature CO adsorption on CoAlBEA results in (i) H-bonded CO, (ii) Co(3+)-CO
      adducts (2,208 cm(-1)) and (iii) a small amount of Co(2+)-CO complexes (2,188 cm(
      1)). In agreement with these results, NO adsorption leads to the appearance of
      (i) NO(+) (2,133 cm(-1), formed with the participation of the zeolite acidic
      hydroxyls), (ii) Co(3+)-NO (1932 cm(-1)), and (iii) a small amount of
      Co(2+)(NO)(2) dinitrosyls (nu(s) = 1,898 and nu(as) = 1,814 cm(-1)). Low
      temperature CO adsorption on CoSiBEA leads to formation of two kinds of Co(2+)-CO
      adducts (2,185 and 2,178 cm(-1)). No Co(3+) cations are detected. In line with
      these results, adsorption of NO reveals the existence of two kinds of
      Co(2+)(NO)(2) dinitrosyls (nu(s) = 1,888 and nu(as) = 1,808 cm(-1) and nu(s) =
      1,878 and nu(as) = 1,799 cm(-1), respectively).

PMID- 17004816
TI  - Gas permeability in polymer- and surfactant-stabilized bubble films.
AB  - The gas permeabilities of thin liquid films stabilized by poly(N
      isopropylacrylamide) (PNIPAM) and PNIPAM-SDS (sodium dodecyl sulfate) mixtures
      are studied using the "diminishing bubble" method. The method consists of forming
      a microbubble on the surface of the polymer solution and measuring the shrinking
      rates of the bubble and the bubble film as the gas diffuses from the interior to
      the exterior of the bubble. PNIPAM-stabilized films exhibit variable thicknesses
      and homogeneities. Interestingly, despite these variable features, the gas
      permeability of the film is determined principally by the structure of the
      adsorbed polymer layer that provides an efficient gas barrier with a value of gas
      permeability coefficient that is comparable to that of an SDS Newton black film.
      In the presence of SDS, both the film homogeneity and the gas permeability
      coefficient increase. These changes are related to interactions of PNIPAM with
      SDS in the solution and at the interface, where coadsorption of the two species
      forms mixed layers that are stable but that are more porous to gas transfer. The
      mixed PNIPAM-SDS layers, studied previously for a single water-air interface by
      neutron reflectivity, are further characterized here in a vertical free-draining
      film using X-ray reflectivity.

PMID- 17004817
TI  - Effect of nanoparticles on the interfacial properties of liquid/liquid and
      liquid/air surface layers.
AB  - An investigation is reported on the interfacial properties of nanometric
      colloidal silica dispersions in the presence of a cationic surfactant. These
      properties are the result of different phenomena such as the particle attachment
      at the interface and the surfactant adsorption at the liquid and at the particle
      interfaces. Since the latter strongly influences the hydrophobicity/lipophilicity
      of the particle, i.e., the particle affinity for the fluid interfacial
      environment, all those phenomena are closely correlated. The equilibrium and
      dynamic interfacial tensions of the liquid/air and liquid/oil interfaces have
      been measured as a function of the surfactant and particle concentration. The
      interfacial rheology of the same systems has been also investigated by measuring
      the dilational viscoelasticity as a function of the area perturbation frequency.
      These results are then crossed with the values of the surfactant adsorption on
      the silica particles, indirectly estimated through experiments based on the
      centrifugation of the dispersions. In this way it has been possible to point out
      the mechanisms determining the observed kinetic and equilibrium features. In
      particular, an important role in the mixed particle-surfactant layer
      reorganization is played by the Brownian transport of particles from the bulk to
      the interface and by the surfactant redistribution between the particle and fluid
      interface.

PMID- 17004818
TI  - Ba adsorption on the stoichiometric and defective TiO(2) (110) surface from first
      principles calculations.
AB  - A theoretical study on Ba adsorption on the rutile TiO(2) (110) surface has been
      carried out by means of plane-wave, plane augmented waves potential, density
      functional theory calculations. A model consisting on a (4 x 1) unit cell, which
      corresponds to coverage of 0.125 monolayer (ML), has been used and several
      potential adsorption sites on the stoichiometric surface have been tried. It has
      been found that the most stable site is with the Ba atom in a position where it
      is bound to two bridging oxygen atoms and an in-plane oxygen atom forming
      equivalent bonds (OB site). The adsorption energy is 0.71 eV referred to the
      formation of Ba bulk and is about 0.3 eV more stable than other adsorption sites.
      The Ba-surface interaction produces some surface relaxation in all cases. The OB
      site is stable at moderate temperatures; however, after extensive molecular
      dynamic calculations it is found that atoms diffuse on the surface by means of a
      jumping mechanism among several stable positions. The presence of bridging oxygen
      vacancies does not alter significantly this picture since the adsorption close to
      defects is not energetically favorable and the atoms tend to move away from
      vacancies. A strong covalent character has been found in the nature of the
      bonding, which contrasts with previous suggestions of the existence of Ba(2+)
      species on the surface. When the coverage is increased to 0.25 ML by adding a Ba
      atom to the supercell, there is a significant repulsion between Ba atoms that
      move away from each other to occupy OB sites. Thus, the adsorption energy values
      per atom diminish. For the stoichiometric surface two equivalent adsorption
      patterns are found, whereas only one is found for the defective surface.

PMID- 17004820
TI  - Competition and coadsorption of di-acids and carboxylic acid solvents on HOPG.
AB  - The self-assemblies of di-acids HOOC-(CH(2))(n)-COOH (n = 20, 18, 16, 14, 12, 10)
      in three solvents hexanoic acid, octanoic acid, and decanoic acid on highly
      oriented pyrolytic graphite (HOPG) were studied with scanning tunneling
      microscopy (STM). In the solvent hexanoic acid, solvent molecules coadsorb with
      HOOC-(CH(2))(n)-COOH (n = 20, 18, 16) via formation of hydrogen bonds. The
      solvent octanoic acid coadsorbs with HOOC-(CH(2))(n)-COOH (n = 20, 18). Decanoic
      acid only coadsorbs with HOOC-(CH(2))(20)-COOH. In each solvent, the trend of
      coadsorption between solvent molecules and di-acid molecules decreases with
      decreasing chain-length of di-acid molecules. These systematic investigations
      suggest that coadsorption of solvent molecules with di-acid solute molecules is
      mainly dependent on the relative hydrogen-bond densities in the formed monolayer.
      This is consistent with the maximization of adsorption heat of the self-assembled
      monolayers of di-acids dissolved in solvents of carboxylic acids.

PMID- 17004821
TI  - Using the constrained DFT approach in generating diabatic surfaces and off
      diagonal empirical valence bond terms for modeling reactions in condensed phases.
AB  - The empirical valence bond (EVB) model provides an extremely powerful way for
      modeling and analyzing chemical reactions in solutions and proteins. However,
      this model is based on the unverified assumption that the off diagonal elements
      of the EVB Hamiltonian do not change significantly upon transfer of the reacting
      system from one phase to another. This ad hoc assumption has been rationalized by
      its consistency with empirically observed linear free energy relationships, as
      well as by other qualitative considerations. Nevertheless, this assumption has
      not been rigorously established. The present work explores the validity of the
      above EVB key assumption by a rigorous numerical approach. This is done by
      exploiting the ability of the frozen density functional theory (FDFT) and the
      constrained density functional theory (CDFT) models to generate convenient
      diabatic states for QM/MM treatments, and thus to examine the relationship
      between the diabatic and adiabatic surfaces, as well as the corresponding
      effective off diagonal elements. It is found that, at least for the test case of
      S(N)()2 reactions, the off diagonal element does not change significantly upon
      moving from the gas phase to solutions and thus the EVB assumption is valid and
      extremely useful.

PMID- 17004819
TI  - Understanding adsorption phenomena: investigation of the dye-cellulose
      interaction.
AB  - To understand the structural factors that control the adsorption of acid dyes
      onto cotton (cellulose), the adsorption of 15 acid dyes from water has been
      studied. An equilibrium exists between dye adsorbed in the cotton and dye in
      solution, and by measurement of the temperature dependence (277-333K) of the
      equilibrium constant, the enthalpy and entropy of binding are obtained. For most
      dyes adsorption is driven by the binding enthalpy, which is ascribed to van der
      Waals forces. Acid dyes consist of an aromatic core with peripheral solubilizing
      groups (generally sulfonates). Dyes in which the sulfonates are on one side of
      the molecule have the largest binding enthalpy. Assuming a binding geometry where
      the sulfonates protrude into water pools in the bulk amorphous regions and as
      much as possible of the dye core touches the surface, then a good correlation
      exists between the binding enthalpy and the summation of 1/r(6) over all the C,
      N, and O dye atoms, where r is the distance of each atom from the cellulose
      surface.

PMID- 17004822
TI  - Study on vapor-liquid equilibria and surface tensions for nonpolar fluids by
      renormalization group theory and density gradient theory.
AB  - An equation of state (EOS) applicable for both the uniform and nonuniform fluids
      is established by using the density-gradient theory (DGT). In the bulk phases,
      the EOS reduces to statistical associating fluid theory (SAFT). By combining the
      EOS with the renormalization group theory (RGT), the vapor-liquid-phase
      equilibria and surface tensions for 10 nonpolar chainlike fluids are investigated
      from low temperature up to the critical point. The obtained results agree well
      with the experimental data.

PMID- 17004823
TI  - Size-dependent enthalpy of condensation.
AB  - A thermodynamic model for the size dependence of enthalpy of condensation,
      DeltaH(con), is discussed. The model is valid over a range of radii where the
      arrangement of surface layer and surface tension remain invariable; it provides a
      way of calculating enthalpy and entropy changes and equilibrium vapor pressures.
      The difference between DeltaH(con) for two liquid bodies of the same chemical
      nature is equal to the variation of the autoadsorption energies on their
      surfaces.

PMID- 17004824
TI  - Molecular force field for ionic liquids III: imidazolium, pyridinium, and
      phosphonium cations; chloride, bromide, and dicyanamide anions.
AB  - This is the third set of parameters of a force field for the molecular simulation
      of ionic liquids, developed within the spirit of the OPLS-AA model and thus
      oriented toward the calculation of equilibrium thermodynamic and structural
      properties. The parameter sets reported here concern the cations
      alkylimidazolium, tetra-alkylphosphonium, and N-alkylpyridinium, and the anions
      chloride, bromide, and dicyanamide. The force field is built in a stepwise manner
      that allows the construction of models for an entire family of cations, with
      alkyl side chains of different length, for example. Due to the transferability of
      the present force field, the ions studied here can be combined with those
      reported in our two previous publications to create a large variety of ionic
      liquids that can be studied by molecular simulation. The parameters reported were
      obtained through different series of ab initio calculations concerning the
      geometry, force constants, torsion energy profiles, and electrostatic charge
      distributions of the ions under study. Validation of the force field consisted of
      comparison with experimental crystal structure and liquid density data.

PMID- 17004825
TI  - How ionic are room-temperature ionic liquids? An indicator of the physicochemical
      properties.
AB  - Room-temperature ionic liquids (RTILs) are liquids consisting entirely of ions,
      and their important properties, e.g., negligible vapor pressure, are considered
      to result from the ionic nature. However, we do not know how ionic the RTILs are.
      The ionic nature of the RTILs is defined in this study as the molar conductivity
      ratio (Lambda(imp)/Lambda(NMR)), calculated from the molar conductivity measured
      by the electrochemical impedance method (Lambda(imp)) and that estimated by use
      of pulse-field-gradient spin-echo NMR ionic self-diffusion coefficients and the
      Nernst-Einstein relation (Lambda(NMR)). This ratio is compared with
      solvatochromic polarity scales: anionic donor ability (Lewis basicity), E(T)(30),
      hydrogen bond donor acidity (alpha), and dipolarity/polarizability (pi), as well
      as NMR chemical shifts. The Lambda(imp)/Lambda(NMR) well illustrates the degree
      of cation-anion aggregation in the RTILs at equilibrium, which can be explained
      by the effects of anionic donor and cationic acceptor abilities for the RTILs
      having different anionic and cationic backbone structures with fixed
      counterparts, and by the inductive and dispersive forces for the various alkyl
      chain lengths in the cations. As a measure of the electrostatic interaction of
      the RTILs, the effective ionic concentration (C(eff)), which is a dominant
      parameter for the electrostatic forces of the RTILs, was introduced as the
      product of Lambda(imp)/Lambda(NMR) and the molar concentration and was compared
      with some physical properties, such as reported normal boiling points and
      distillation rates, glass transition temperature, and viscosity. A decrease in
      C(eff) of the RTILs is well correlated with the normal boiling point and
      distillation rate, whereas the liquid-state dynamics is controlled by a subtle
      balance between the electrostatic and other intermolecular forces.

PMID- 17004826
TI  - Competing evaporation and condensation processes during the boiling of methane.
AB  - The atomistic mechanism of the boiling of methane is explored from molecular
      dynamics simulations. The liquid --> vapor transition is initiated by local
      density fluctuations resulting in a nanometer-sized domain that exhibits both
      liquid and vapor characteristics. Though the rates of evaporation and
      condensation events increase dramatically in this area, the overall balance
      exhibits only a marginal net rate of evaporation. Growth of the precritical
      domain leads to the nucleation of a vapor phase in which isolated methane
      molecules are confined by a liquid-vapor interface. After crossing the transition
      state, the system experiences progressive destabilization of the liquid phase and
      the evaporation processes clearly outnumber the condensation events.

PMID- 17004827
TI  - Density functional theory study of hydrogen bonding in ionic molecular materials.
AB  - Crystal structures are usually described in geometric terms. However, it is the
      energetics of intermolecular interactions that determine the chemical and
      physical properties of molecular materials.(1) In this paper, we use density
      functional theory (DFT) in combination with numerical basis sets to analyze the
      hydrogen bonding interactions in a family of novel ionic molecular materials. We
      find that the calculated binding energies are consistent with those of other
      ionic hydrogen bonded systems. We also examine electron density distributions for
      the systems of interest to gain insight into the nature of the hydrogen bonding
      interaction and investigate the effects of different aspects of the crystal field
      on the geometry of the hydrogen bond.

PMID- 17004828
TI  - Entropy of water in the hydration layer of major and minor grooves of DNA.
AB  - Transport properties (translational and rotational) of water in the two grooves
      of the B-DNA duplex are known to be different from those in the bulk. Here, we
      use a recently developed theoretical scheme to compute the entropies of water
      molecules in both of the grooves of DNA and compare them with that in the bulk.
      The scheme requires as input both translational and rotational velocity
      autocorrelation function (C(V)(t) and C(omega)(t), respectively) data. These
      velocity autocorrelation functions were computed from an atomistic MD simulation
      of a B-DNA duplex (36 base pairs long) in explicit water (TIP3P). The average
      values of the entropy of water at 300 K in both of the grooves of DNA (the TS
      value in the major groove is 6.71 kcal/mol and that in the minor groove is 6.41
      kcal/mol) are found to be significantly lower than that in bulk water (the TS
      value is 7.27 kcal/mol). Thus, the entropic contribution to the free energy
      change (TDeltaS) of transferring a minor groove water molecule to the bulk is
      0.86 kcal/mol and of transferring a major groove water to the bulk is 0.56
      kcal/mol at 300 K, which is to be compared with 1.44 kcal/mol for melting of ice
      at 273 K. We also calculate the energy of interaction of each water molecule with
      the rest of the atoms in the system and hence calculate the chemical potential
      (Helmholtz free energy per water molecule, A = E - TS) in the different domains.
      The identical free energy value of water molecules in the different domains
      proves the robustness of the scheme. We propose that the configurational entropy
      of water in the grooves can be used as a measure of the mobility (or
      microviscosity) of water molecules in a given domain.

PMID- 17004829
TI  - Origin of the dynamic transition upon pressurization of crystalline proteins.
AB  - We study the role of hydration water in the dynamic transition of low-hydrated
      proteins upon pressurization found recently (Meinhold, L.; Smith, J. C. Phys.
      Rev. E 2005, 72, 061908). Clustering and percolation of water in the hydration
      shells of protein molecules in crystalline Staphylococcal nuclease are analyzed
      at various pressures. The number of water molecules in the hydration shell
      increases and the hydrogen-bonded network of hydration water spans with
      increasing pressure. The dynamic transition of protein occurs when the spanning
      water network exists with the probability of about 50% and hydration water shows
      large density fluctuations. Formation of a spanning water network upon
      pressurization promotes protein dynamics as in the case of the dynamic transition
      with increasing hydration. Properties of hydration water in various thermodynamic
      states and their influence on biological function are discussed.

PMID- 17004830
TI  - Raman microscopy for the chemometric analysis of tumor cells.
AB  - Raman spectroscopy is recognized as a tool for chemometric analysis of biological
      materials due to the high information content relating to specific physical and
      chemical qualities of the sample. Thirty cells belonging to two different
      prostatic cell lines, PNT1A (immortalized normal prostate cell line) and LNCaP
      (malignant cell line derived from prostate metastases), were mapped using Raman
      microscopy. A range of spectral preprocessing methods (partial least-squares
      discriminant analyses (PLSDAs), principal component analyses (PCAs), and adjacent
      band ratios (ABRs)) were compared for input into linear discriminant analysis to
      model and classify the two cell lines. PLSDA and ABR were able to correctly
      classify 100% of cells into benign and malignant groups, while PLSDA correctly
      classified a greater proportion of individual spectra. PCA was used to image the
      distribution of various biochemicals inside each cell and confirm differences in
      composition/distribution between benign and malignant cell lines. This study has
      demonstrated that PLSDAs and ABRs of Raman data can identify subtle differences
      between benign and malignant prostatic cells in vitro.

PMID- 17004832
TI  - Thermodynamic and infrared analyses of the interaction of chlorpromazine with
      phospholipid monolayers.
AB  - An investigation has been made of the interaction between chlorpromazine (CPZ)
      and monolayers of 1,2-dipalmitoyl-sn-3-glycerophosphatidylcholine (DPPC) and 1,2
      dipalmitoyl-sn-3-glycero[phospho-rac-(1-glycerol)] (DPPG), both at the air/water
      interface and in transferred Langmuir-Blodgett films. The Gibbs free energy,
      DeltaG, and the compressibility modulus (C(S)(-1)), obtained from the surface
      pressure isotherms, indicated changes in the in-plane interactions of CPZ/DPPG
      mixed monolayers, with positive values of DeltaG. The arrangement of CPZ in the
      zwitterionic DPPC monolayers causes a weaker interaction in CPZ/DPPC mixed
      monolayers, with the DeltaG fluctuating around zero. IR measurements in
      transferred monolayers showed that CPZ did not affect the conformational order of
      the acyl chains, its effects being limited to the bands corresponding to the
      headgroups. Furthermore, since no shift was observed for the acyl chain bands,
      the phase transition induced by CPZ is not a liquid expanded (LE) to liquid
      condensed (LC) transition, as the latter is associated with chain ordering. Taken
      together, the IR and compressibility results demonstrate that the effect from CPZ
      cannot be correlated with temperature changes in the subphase for pure
      monolayers, in contrast to models proposed by other authors.

PMID- 17004831
TI  - Mechanism of action of anticancer titanocene derivatives: an insight from quantum
      chemical calculations.
AB  - Titanocene derivatives exhibit high potential in the treatment of cisplatin
      resistant tumor types. Density functional theory calculations were performed on
      the hydrated form of five drug candidates differing in the pendant arms attached
      to the aromatic rings. A qualitative correlation has been found between the
      experimentally measured anticancer activity of alkylammonium-functionalized
      titanocene derivatives and the computed free energy change of the proton-induced
      dissociation reaction of these compounds. The results indicate that differences
      in the cytotoxic activities could be related to the solvation properties of the
      protolysis products, whereas no correlation was found with gas-phase properties
      of these molecules. Contrary to the free energy change of the protolysis
      reaction, other molecular properties, such as the geometrical parameters or the
      binding energies of the cyclopentadienyl rings in solution, do not correlate with
      the in vitro cytotoxic activity of these drug candidates.

PMID- 17004833
TI  - Fluorescence study of DNA binding and bending by EcoRI DNA methyltransferase.
AB  - We have applied fluorescence anisotropy and fluorescence resonance energy
      transfer (FRET) techniques to study the interaction between EcoRI DNA
      methyltransferase (M.EcoRI) and its target DNA in solution. Upon binding with
      M.EcoRI, the dsDNA containing GAATTC bends to flip out the second adenine for
      methylation. The binding affinity of M.EcoRI to two dsDNA fragments (20 and 38
      bp) was studied with fluorescence anisotropy. Their binding constants at
      different temperatures from 20 to 40 degrees C were obtained, and the
      thermodynamic parameters of binding were derived. The results showed that M.EcoRI
      had a higher binding affinity to the short dsDNA strand than to the long one, and
      its binding to DNA was primarily entropy-driven. By labeling the 5' ends of the
      20-bp dsDNA with two fluorescent dyes, fluorescein (FAM) and tetramethylrhodamine
      (TMR), we were able to monitor the enhanced TMR fluorescence in the presence of
      M.EcoRI. The end-to-end distance of the dsDNA determined from the FRET efficiency
      was changed from 72.4 to 63.4 A, and the DNA bending angle was estimated as 57.8
      degrees .

PMID- 17004834
TI  - Characterization of nucleobase-amino acid stacking interactions utilized by a DNA
      repair enzyme.
AB  - The present work characterizes the gas-phase stacking interactions between four
      aromatic amino acid residues (histidine, phenylalanine, tyrosine, and tryptophan)
      and adenine or 3-methyladenine due to the proposed utilization of these
      interactions by enzymes that repair DNA alkylation damage. The MP2 potential
      energy surfaces of the stacked dimers are considered as a function of four
      variables (vertical displacement, angle of rotation, horizontal displacement, and
      tilt angle) using a variety of basis sets. It is found that the maximum stacking
      interaction energy decreases with the amino acid according to TRP > TYR
      approximately HIS > PHE for both nucleobases. However, the magnitude of the
      stacking interaction significantly increases upon alkylation (by 50-115%).
      Comparison of the stacking energies calculated using our surface scans to those
      estimated from experimental crystal structures indicates that the stacking
      interactions within the active site of 3-methyladenine DNA glycosylase can
      account for 65-75% of the maximum possible stacking interaction between the
      relevant molecules. The decrease in stacking in the crystal structure arises due
      to significant differences in the relative orientations of the nucleobase and
      amino acid. Nevertheless, alkylation is found to significantly increase the
      stacking energy when the crystal structure geometries are considered. Our
      calculations provide computational support for suggestions that alkylation
      enhances the stacking interactions within the active site of DNA repair enzymes,
      and they give a measure of the magnitude of this enhancement. Our results suggest
      that alkylation likely plays a more important role in substrate identification
      and removal than the nature of the aromatic amino acid that interacts with the
      substrate via stacking interactions.

PMID- 17004835
TI  - Exploring bovine pancreatic trypsin inhibitor phase transitions.
AB  - This paper presents an investigation of the phase diagram of BPTI (bovine
      pancreatic trypsin inhibitor)/350 mM KSCN at pH 4.9 by direct observation and
      numerical simulations. We report optical microscopy and light and X-ray
      scattering experiments coupled with theoretical data analysis using numerical
      tools. The phase diagram is thoroughly determined, as a function of temperature.
      Two polymorphs are observed by video microscopy and their solubility measured. In
      this phase diagram, the liquid-liquid phase separation (LLPS) is metastable with
      respect to the solid-liquid phase separation. Above the T(L-L) boundary curve,
      solutions are composed of a mixture of BPTI monomers and decamers. Attractive
      interactions are stronger between decamers than between monomers. Below the T(L
      L) boundary curve, the dense phase is highly concentrated in protein and composed
      of BPTI decamers alone. Thus, the driving force for liquid-liquid or liquid-solid
      phase separation is the attraction between decamers at low pH. The structure
      factors of the dense phases are characteristic of repulsive dense phases because
      of a hard sphere repulsion core, meaning that in the dense phase proteins are
      actually in contact (interparticle distance of 53 A). In agreement with the
      Oswald rule of stages, LLPS occurs prior to and impedes the solid nucleation.

PMID- 17004836
TI  - Conductance of alpha-helical peptides trapped within molecular junctions.
AB  - Self-assembled monolayers of alpha-helical peptides on a gold surface were
      employed as model systems for the investigation of mediated electron transfer.
      The peptides contained 14, 15, 16, and 17 amino acid residues. The measurements
      of electron transmission through single molecules of helical peptides were
      performed using scanning tunneling spectroscopy (STS). The molecules were trapped
      between the gold tip and the substrate. Electrical contact between the molecule
      and the gold probe was achieved by the use of peptides containing thiol groups
      present at each end of the helix. The conductance behavior of the peptides was
      examined as a function of tip-substrate distance at fixed bias voltage.
      Measurements performed with peptides containing different numbers of amino acid
      residues indicate that the distance dependence of electron transmission through
      an alpha-helix is weaker than that through simple n-alkyl bridges.

PMID- 17004837
TI  - Glass transition temperature of glucose, sucrose, and trehalose: an experimental
      and in silico study.
AB  - Isothermal-isobaric molecular dynamics simulations are used to calculate the
      specific volume of models of different amorphous carbohydrates (glucose, sucrose,
      and trehalose) as a function of temperature. Plots of specific volume vs
      temperature exhibit a characteristic change in slope when the amorphous systems
      change from the glassy to the rubbery state. The intersection of the regression
      lines of data below (glassy state) and above (rubbery state) the change in slope
      provides the glass transition temperature (T(g)). These predicted glass
      transition temperatures are compared to experimental T(g) values as obtained from
      differential scanning calorimetry measurements. As expected, the predicted values
      are systematically higher than the experimental ones (about 12-34 K) as the
      cooling rates of the modeling methods are about a factor of 10(12) faster.
      Nevertheless, the calculated trend of T(g) values agrees exactly with the
      experimental trend: T(g)(glucose) < T(g)(sucrose) < T(g)(trehalose). Furthermore,
      the relative differences between the glass transition temperatures were also
      computed precisely, implying that atomistic molecular dynamics simulations can
      reproduce trends of T(g) values in amorphous carbohydrates with high quality.

PMID- 17004838
TI  - Understanding the enzymatic activity of 4-oxalocrotonate tautomerase and its
      mutant analogues: a computational study.
AB  - The effect of replacing arginine residues (Arg) with citrulline residues (Cit) in
      the binding site of 4-oxalocrotonate tautomerase (4-OT) was investigated with
      force field molecular dynamics and hybrid quantum mechanics/molecular mechanics
      studies. It is found that the Arg61Cit mutation has only minor effects on the
      k(cat) and K(M) values determined experimentally because of the flexibility of
      this residue. The decrease in k(cat) and increase in K(M) for the Arg11Cit and
      Arg39Cit mutations are due to the disruption of the binding site, which arises
      from repulsive interactions with neighboring residues. The results of this
      investigation shed new light on the effects of mutations in the binding site of 4
      OT and consequently on how the enzyme binds the active substrate.

PMID- 17004839
TI  - Understanding electron attachment to the DNA double helix: the thymidine
      monophosphate-adenine pair in the gas phase and aqueous solution.
AB  - Electron attachment to the 2'-deoxythymidine-5'-monophosphate-adenine pairs (5'
      dTMPH-A and 5'-dTMP(-)-A) has been investigated at a carefully calibrated level
      of theory (B3LYP/DZP++) to investigate the electron-accepting properties of
      thymine (T) in the DNA double helix under physiological conditions. All molecular
      structures have been fully optimized in vacuo and in solution. The adiabatic
      electron affinity of 5'-dTMPH-A in the gas phase has been predicted to be 0.67
      eV. Solvent effects greatly increase the electron capture ability of 5'-dTMPH-A.
      In fact, the adiabatic electron affinity increases to 2.04 eV with solvation. The
      influence of the solvent environment on the electron-attracting properties of 5'
      dTMPH-A arises not only from the stabilization of the corresponding radical anion
      through charge-dipole interactions, but also by changing the distribution of the
      unpaired electron in the molecular system. The unpaired electron is covalently
      bound even during vertical attachment, due to the solvent effects. Solvent
      effects also weaken the pairing interaction in the thymidine monophosphate
      adenine complexes. The phosphate deprotonation is found to have a relatively
      minor influence on the capture of electrons by the 5'-dTMPH-A species in aqueous
      solution. The electron distributions, natural population analysis, and
      geometrical features of the models examined illustrate that the influence of the
      phosphate deprotonation is limited to the phosphate moiety in aqueous solution.
      Therefore, it is reasonable to expect that electron attachment to nucleotides
      will be independent of monovalent counterions in the vicinity of the phosphate
      group in aqueous solution.

PMID- 17004840
TI  - Hydrogen bonding pathways in human dihydroorotate dehydrogenase.
AB  - Dihydroorotate dehydrogenase (DHOD) catalyzes the only redox reaction in the
      pathway for pyrimidine biosynthesis. In this reaction, a proton is transferred
      from a carbon atom of the substrate to a serine residue, and a hydride is
      transferred from another carbon atom of the substrate to a cofactor. The
      deprotonation of the substrate is postulated to involve a proton relay mechanism
      along a hydrogen bonding pathway in the active site. In this paper, molecular
      dynamics simulations are used to identify and characterize potential hydrogen
      bonding pathways that could facilitate the redox reaction catalyzed by human
      DHOD. The observed pathways involve hydrogen bonding of the active base serine to
      a water molecule, which is hydrogen bonded to the substrate carboxylate group or
      a threonine residue. The threonine residue is positioned to enable proton
      transfer to another water molecule leading to the bulk solvent. The impact of
      mutating the active base serine to cysteine is also investigated. This mutation
      is found to increase the average donor-acceptor distances for proton and hydride
      transfer and to disrupt the hydrogen bonding pathways observed for the wild-type
      enzyme. These effects could lead to a significant decrease in enzyme activity, as
      observed experimentally for the analogous mutant in Escherichia coli DHOD.

PMID- 17004841
TI  - Conjugated chromophore near the quantum-confined cadmium sulfide cluster:
      quenched photoluminescence and enhanced two-photon absorption.
AB  - Quenching effect of the photoluminescence of 1,2,4,5-tetrakis(4
      pyridylvinyl)benzene in the presence of CdS colloids stabilized by inverse
      micelles was observed. The observed regularities of luminescence quenching by the
      quenchers of different size were studied. An increase in the two-photon
      absorption cross section (6.5 times higher) and in the two-photon-induced
      fluorescence intensity was observed for the composite solution when pumped by 740
      nm laser irradiation. The results are in accord with theoretical prediction of
      enhancement of third-order optical nonlinearity of quantum-confined
      semiconductor.

PMID- 17004842
TI  - Formation and decomposition of ethane, propane, and carbon dioxide hydrates in
      silica gel mesopores under high pressure.
AB  - The experimental data on decomposition temperatures for the gas hydrates of
      ethane, propane, and carbon dioxide dispersed in silica gel mesopores are
      reported. The studies were performed at pressures up to 1 GPa. It is shown that
      the experimental dependence of hydrate decomposition temperature on the size of
      pores that limit the size of hydrate particles can be described on the basis of
      the Gibbs-Thomson equation only if one takes into account changes in the shape
      coefficient that is present in the equation; in turn, the value of this
      coefficient depends on a method of mesopore size determination. A mechanism of
      hydrate formation in mesoporous medium is proposed. Experimental data providing
      evidence of the possibility of the formation of hydrate compounds in hydrophobic
      matrixes under high pressure are reported. Decomposition temperature of those
      hydrate compounds is higher than that for the bulk hydrates of the corresponding
      gases.

PMID- 17004843
TI  - Spherical cell approach for the effective viscosity of suspensions.
AB  - In the present paper, the spherical cell approach is employed for addressing the
      effective viscosity of suspensions of spherical particles. The proposed
      derivation is based on the only assumption which constitutes the essence of the
      spherical cell approach: a representative part of the suspension is a spherical
      cell which contains a particle surrounded by the continuous phase. In contrast
      with the previous studies on this topic, no additional assumptions are used in
      the present analysis. The general method of derivation and the final result,
      which represents the effective viscosity as a function of the solid-phase volume
      fraction, are compared with earlier studies where the spherical cell approach was
      applied for describing the effective viscosity.

PMID- 17004844
TI  - Phase diagram and glass transition of confined benzene.
AB  - We used differential scanning calorimetry, neutron scattering, and proton NMR to
      investigate the phase behavior, the structure, and the dynamics of benzene
      confined in a series of cylindrical mesoporous materials MCM-41 and SBA-15 with
      pore diameters, d, between 2.4 and 14 nm. With this multitechnique approach, it
      was possible to determine the structure and, for the first time to our knowledge,
      the density of confined benzene as a function of temperature and pore size. Under
      standard cooling rates, benzene partially crystallizes in SBA-15 matrixes (4.7
      <or= d <or= 14 nm) but not in MCM-41 (2.4 <or= d <or= 3.5 nm). Structure factors
      of the confined phases were recorded at different temperatures and compare to
      those of the bulk. The confined liquid has the same structure as the bulk above
      the bulk melting point. In SBA-15, the confined crystals are defective and have
      the same structure as the bulk. In MCM-41, the liquid undergoes a glass
      transition at low temperature regardless of the cooling rate or the thermal
      history of the sample. The density as a function of temperature was measured by
      neutron scattering contrast matching, and the glass transition temperatures were
      determined from the density versus temperature curves. The pore size dependence
      of T(g) does not show any evidence of finite size effects. A temperature versus
      pore diameter phase diagram of confined benzene is proposed combining liquid,
      supercooled liquid, crystal states, and glassy states. NMR relaxation time
      measurements showed that the dynamics of the confined liquids are slower than
      those of the bulk above its melting point. In the partially crystallized samples,
      the liquid and the crystal have the same relaxation times. The activation
      energies of reorientation motions in the confined phases, determined from spin
      lattice relaxation times, are smaller than the bulk ones.

PMID- 17004845
TI  - Psychomotor speed: possibly a new marker for overtraining syndrome.
AB  - Overtraining syndrome (OTS) is a major threat for performance and health in
      athletes. OTS is caused by high levels of (sport-specific) stress in combination
      with too little regeneration, which causes performance decrements, fatigue and
      possibly other symptoms. Although there is general consensus about the causes and
      consequences, many different terminologies have been used interchangeably. The
      consequences of overreaching and overtraining are divided into three categories:
      (i) functional overreaching (FO); (ii) non-functional overreaching (NFO); and
      (iii) OTS. In FO, performance decrements and fatigue are reversed within a pre
      planned recovery period. FO has no negative consequences for the athlete in the
      long term; it might even have positive consequences. When performance does not
      improve and feelings of fatigue do not disappear after the recovery period,
      overreaching has not been functional and is thus called NFO. OTS only applies to
      the most severe cases. NFO and OTS could be prevented using early markers, which
      should be objective, not manipulable, applicable in training practice, not too
      demanding, affordable and should be based on a sound theoretical framework. No
      such markers exist up to today. It is proposed that psychomotor speed might be
      such a marker. OTS shows similarities with chronic fatigue syndrome and with
      major depression (MD). Through two meta-analyses, it is shown that psychomotor
      slowness is consistently present in both syndromes. This leads to the hypothesis
      that psychomotor speed is also reduced in athletes with OTS. Parallels between
      commonly used models for NFO and OTS and a threshold theory support the idea that
      psychomotor speed is impaired in athletes with NFO or OTS and could also be used
      as an early marker to prevent NFO and/or OTS.

PMID- 17004846
TI  - Exercise and psychobiological processes: implications for the primary prevention
      of coronary heart disease.
AB  - Interventions that reduce the magnitude of psychobiological responses are
      justified, at least in part, by the notion that exaggerated responses to stress
      can have detrimental effects on health. The biological processes underlying the
      association between stress and coronary heart disease (CHD) are thought to
      involve haemodynamic, neuroendocrine, inflammatory and haemostatic pathways. One
      of the many recognised benefits of exercise is in buffering physiological
      responses to psychosocial stressors, which is thought to be partly mediated by
      sympatho-inhibitory mechanisms, although other potentially important
      psychobiological processes such as inflammatory, neuroendocrine and haemostatic
      pathways have gained little attention. Thus, the present review focuses on the
      role of exercise in buffering psychobiological processes, particularly in
      relation to pathways that are directly relevant for reducing CHD risk. There are
      inconsistencies in the literature regarding the effects of exercise on
      cardiovascular responses to stressors, which may in part be accounted for by
      differences in experimental design, characteristics of participants, inadequate
      assessment of physical fitness, and the confounding effects of acute exercise.
      However, new emerging evidence suggests that exercise promotes an anti
      inflammatory environment and increases tissue sensitivity to glucocorticoids,
      which may have implications for the effects of exercise on stress-induced
      inflammatory pathways. Future work should focus on the efficacy of exercise for
      promoting anti-inflammatory pathways in relation to psychosocial stress.

PMID- 17004847
TI  - Recurrent subluxation of the peroneal tendons.
AB  - Recurrent peroneal tendon subluxation is an uncommon sports-related injury. The
      retrofibular groove is formed not by the concavity of the fibula itself, but by a
      relatively pronounced ridge of collagenous soft tissue blended with the
      periosteum that extends along the posterolateral lip of the distal fibula. The
      shape of the groove is primarily determined by this thick fibrocartilagenous
      periosteal cushion, and not by the bone itself. The superior peroneal retinaculum
      is extremely variable in width, thickness and insertional patterns. Peroneal
      tendon subluxation is commonly associated with longitudinal splits in the
      peroneus brevis tendon and lateral ankle instability. Disruption of the lateral
      collateral ankle ligaments places considerable strain on the superior peroneal
      retinaculum. This explains why the two conditions commonly coexist. In recurrent
      subluxation, patients usually give a history of previous ankle injury, which may
      have been misdiagnosed as a sprain. An unstable ankle that gives way or is
      associated with a popping or snapping sensation is another common complaint. The
      peroneal tendons may actually be seen subluxing anteriorly on the distal fibula
      during ambulation. The role of imaging has been debated, and the diagnosis and
      management plan are based on clinical evidence. Conservative management may be
      attempted in acute dislocations, and can be successful in up to 50% of patients,
      although there is a trend for operative management in athletes. Recurrent
      dislocations should be managed surgically. Five basic categories of repair have
      been described: (i) anatomical reattachment of the retinaculum; (ii) bone-block
      procedures; (iii) reinforcement of the superior peroneal retinaculum with local
      tissue transfers; (iv) rerouting the tendons behind the calcaneofibular ligament;
      and (v) groove deepening procedures. However, it is impossible to determine from
      the relatively small series which procedure is superior. If an anatomical
      approach to treating the pathology is utilised, reattachment of the superior
      retinaculum seems a most appropriate technique. Randomised controlled 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 described
      make such study difficult.

PMID- 17004848
TI  - The effects of the menstrual cycle on anterior knee laxity: a systematic review.
AB  - Female athletes are at a 4- to 6-fold increased risk of anterior cruciate
      ligament (ACL) injury compared with male athletes. There are several medical,
      emotional and financial burdens associated with these injuries. Sex hormones may
      be involved in the ACL injury disparity, with potential associations reported
      between phases of the menstrual cycle and ACL injury rates. The reported
      relationships between ACL injury and menstrual status may be related to
      associated changes in ligament mechanical properties from cyclic fluctuations of
      female sex hormones. A PubMed electronic database literature search, including
      MEDLINE (1966-2005) and CINAHL (1982-2005), with the search terms 'menstrual
      cycle' and 'knee laxity' was used for this systematic review. Studies were
      included in this systematic review if they were prospective cohort studies and
      investigated the association between the menstrual cycle and anterior knee laxity
      in females. Nine prospective cohort studies, published as 11 articles, were
      included in the systematic review. Six of nine studies reported no significant
      effect of the menstrual cycle on anterior knee laxity in women. Three studies
      observed significant associations between the menstrual cycle and anterior knee
      laxity. These studies all reported the finding that laxity increased during the
      ovulatory or post-ovulatory phases of the cycle. A meta-analysis, which included
      data from all nine reviewed studies, corroborated this significant effect of
      cycle phase on knee laxity (F-value = 56.59, p = 0.0001). In the analyses, the
      knee laxity data measured at 10-14 days was >15-28 days which was >1-9 days.
      Future studies testing the relationship between the menstrual cycle and
      potentially associated parameters should consider the limitations outlined in
      this article and control for potential biases and confounders. Power analyses
      should be utilised. Subjects should be randomly entered into the studies at
      alternate points in the cycle, and standard and consistent data acquisition and
      reporting methods should be utilised. Future studies should clearly define what
      constitutes a 'normal' cycle and appropriate control subjects should be utilised.
      Furthermore, there is a need to define cycle phase (and timing within cycle
      phase) with actual hormone levels rather than a day of the cycle. Although
      hormone confirmations were provided in many of the studies that selected specific
      days to depict a particular cycle for all women, it is unknown from these data if
      they truly captured times of peak hormone values in all women. A combined
      systematic review and meta-analysis of the literature indicate that the menstrual
      cycle may have an effect on anterior-posterior laxity of the knee; however,
      further investigation is needed to confirm or reject this hypothesis.

PMID- 17004849
TI  - Thermoregulation during exercise in individuals with spinal cord injuries.
AB  - The increased participation in wheelchair sports in conjunction with
      environmental challenges posed by the most recent Paralympic venues has
      stimulated interest into the study of thermoregulation of wheelchair users. This
      area is particularly pertinent for the spinal cord injured as there is a loss of
      vasomotor and sudomotor effectors below the level of spinal lesion. Studies
      within this area have examined a range of environmental conditions, exercise
      modes and subject populations. During exercise in cool conditions (15-25 degrees
      C), trained paraplegic individuals (thoracic or lumbar spinal lesions) appear to
      be at no greater risk of thermal injury than trained able-bodied individuals,
      although greater heat storage for a given metabolic rate is evident. In warm
      conditions (25-40 degrees C), trained subjects again demonstrate similar core
      temperature responses to the able-bodied for a given relative exercise load but
      elicit increased heat storage within the lower body and reduced whole-body sweat
      rates, increasing the risk of heat injury. The few studies examining a wide range
      of lesion levels have noted that, for paraplegic individuals where heat
      production is matched by available sweating capacity, excessive heat strain may
      be offset. Studies relating to tetraplegic subjects (cervical spinal lesions) are
      fewer in number but have consistently shown this population to elicit much faster
      rates of core and skin temperature increase and thermal imbalance in both cool
      and warm conditions than paraplegic individuals. These responses are due to the
      complete absence or severely reduced sweating capacity in tetraplegic subjects.
      During continuous exercise protocols, the main thermal stressor for tetraplegic
      subjects appears to be environmental heat gain, whereas during an intermittent
      type exercise protocol it appears to be metabolic heat production. Fluid losses
      during exercise and heat retention during passive recovery from exercise are
      related to lesion level. Future research is recommended to focus on the specific
      role of absolute and relative metabolic rates, sweating responses, training
      status and more sport- and vocation-specific exercise protocols.

PMID- 17004852
TI  - Imaging of the pituitary and sella turcica.
AB  - The pituitary gland is housed in the sella turcica and has vital endocrinologic
      functions. It lies in close proximity to numerous vital structures, including the
      optic chiasm, sphenoid sinus, cavernous sinus and hypothalamus. An understanding
      of the function, anatomy and embryology of the pituitary gland and its
      surrounding structures is vital to understanding its normal appearance, as well
      as in evaluating the broad spectrum of pathology that can involve the pituitary
      gland. Imaging of pathology in the sellar region, including pituitary adenomas,
      meningiomas, craniopharyngiomas and aneurysms, plays an important role in guiding
      treatment decisions. Modern imaging techniques are also important in evaluating
      the pituitary gland after surgery.

PMID- 17004853
TI  - Sellar lesions and visual loss: key concepts in neuro-ophthalmology.
AB  - The pituitary gland serves an essential role in the activity and regulation of
      the endocrine system. Mass lesions within the pituitary gland account for
      approximately 10-15% of intracranial neoplasms. Patients with pituitary adenomas
      may present with endocrine dysfunction or neuro-ophthalmic pathology, resulting
      from compression of surrounding structures, most notably the optic chiasm. Visual
      deficits from chiasmal tumors may manifest as visual field defects, visual loss,
      diplopia, nystagmus and visual hallucinations. Visual field defects are the most
      commonly reported presenting visual symptom. The specific visual field defect
      usually results from the anatomic compression of the tumor upon the optic chiasm.
      It is important to recognize characteristic visual deficits in the diagnosis and
      treatment of chiasmal tumors.

PMID- 17004854
TI  - Prolactin-secreting tumors: what's new?
AB  - Prolactinomas are a common cause of reproductive/sexual dysfunction. Once other
      causes of hyperprolactinemia have been excluded with a careful history and
      physical examination, routine chemistries, a pregnancy test and a thyroid
      stimulating hormone, imaging with magnetic resonance imaging or computed
      tomography will delineate the size and extent of the tumor. Medical therapy with
      cabergoline or bromocriptine is the initial treatment of choice. When infertility
      is the primary indication for treatment, bromocriptine use has an extensive
      safety experience and is preferred by some clinicians. However, for other
      indications, cabergoline appears to be more efficacious and better tolerated.
      Transsphenoidal surgery remains an option, especially for patients with
      microadenomas, when medical therapy is ineffective or not tolerated.

PMID- 17004850
TI  - Central fatigue: the serotonin hypothesis and beyond.
AB  - The original central fatigue hypothesis suggested that an exercise-induced
      increase in extracellular serotonin concentrations in several brain regions
      contributed to the development of fatigue during prolonged exercise. Serotonin
      has been linked to fatigue because of its well known effects on sleep, lethargy
      and drowsiness and loss of motivation. Several nutritional and pharmacological
      studies have attempted to manipulate central serotonergic activity during
      exercise, but this work has yet to provide robust evidence for a significant role
      of serotonin in the fatigue process. However, it is important to note that brain
      function is not determined by a single neurotransmitter system and the
      interaction between brain serotonin and dopamine during prolonged exercise has
      also been explored as having a regulative role in the development of fatigue.
      This revised central fatigue hypothesis suggests that an increase in central
      ratio of serotonin to dopamine is associated with feelings of tiredness and
      lethargy, accelerating the onset of fatigue, whereas a low ratio favours improved
      performance through the maintenance of motivation and arousal. Convincing
      evidence for a role of dopamine in the development of fatigue comes from work
      investigating the physiological responses to amphetamine use, but other
      strategies to manipulate central catecholamines have yet to influence exercise
      capacity during exercise in temperate conditions. Recent findings have, however,
      provided support for a significant role of dopamine and noradrenaline
      (norepinephrine) in performance during exercise in the heat. As serotonergic and
      catecholaminergic projections innervate areas of the hypothalamus, the
      thermoregulatory centre, a change in the activity of these neurons may be
      expected to contribute to the control of body temperature whilst at rest and
      during exercise. Fatigue during prolonged exercise clearly is influenced by a
      complex interaction between peripheral and central factors.

PMID- 17004855
TI  - Oncogenesis and mutagenesis of pituitary tumors.
AB  - Although pituitary tumors may be present in up to 10% of the population, the
      pathophysiology of these lesions is not well characterized. Pituitary tumors are
      composed of monoclonal cell populations with disrupted control of replication
      pathways. The oncogenes and tumor suppressor genes that are common in other
      malignancies (i.e. jun, fos, myc, and p53) are rarely involved in the development
      of these tumors. However, oncogenes, such as gsp, can be present in up to 40% of
      hormonally active adenomas. The process of pituitary oncogenesis further appears
      to involve oncogenes such as cyclin E, cyclin D1, and the pituitary tumor
      transforming gene (PTTG). Finally, the cAMP signaling cascade plays a significant
      role in generation of both benign and malignant pituitary tumors. In this review,
      the biology of pituitary adenomas is explored with a special emphasis on
      potential targets for the development of targeted therapeutics.

PMID- 17004856
TI  - An approach to the evaluation and treatment of Cushing's disease.
AB  - Cushing's syndrome is an uncommon disorder involving dysregulation of the
      hypothalamic-pituitary-adrenal axis resulting in endogenous hypercortisolemia. It
      has multiple causes, but most commonly is due to hypersecretion of corticotropin
      from the pituitary gland, called Cushing's disease. The diagnosis of Cushing's
      syndrome remains a challenge to clinicians because routine hormonal assays can
      have significant overlap in pathological and normal states. We will review an
      approach to evaluating patients with suspected cortisol excess. We will also
      discuss treatment options and post-surgical assessment for those diagnosed with
      Cushing's disease.

PMID- 17004857
TI  - Changing paradigms in the surgical and medical management of acromegaly.
AB  - Acromegaly is a serious, but rare, form of pituitary tumor. This review will
      discuss recent progress in surgical and medical care, highlight data on choosing
      the order for primary and secondary therapy and preview emerging drugs. Several
      controversial areas will be discussed, including the role of preselecting
      subjects for drug responsiveness, whether or not a brief course of medical
      therapy before surgery improves outcomes, and trials of combination drug therapy.
      It is hoped that earlier diagnosis, referral of patients to dedicated pituitary
      surgeons or neuroendocrinology teams, development of more effective and
      affordable drugs, and further advances in surgery and radiotherapy will continue
      to improve the morbidity and mortality from acromegaly.

PMID- 17004858
TI  - Treatment of infertility in women with pituitary tumors.
AB  - Due to the pituitary's critical position, a pituitary tumor may disrupt gonadal
      function, either by its expanding size or the inappropriate secretion of
      hormones. Menstrual cycles may be disrupted even without frank hypogonadism,
      particularly in the case of hormone-secreting adenomas. Despite optimal medical
      and surgical management of pituitary tumors, ovulation-induction therapy with
      gonadotropins is often required to restore fertility in these women. This article
      will provide an overview of the therapeutic options available for women with
      infertility resulting from pituitary tumors. Treatment strategies including
      dopamine agonists, gonadotropins and the role of assisted reproductive
      technologies will be discussed. Unique pregnancy considerations in the female
      patient with hypopituitarism will also be addressed.

PMID- 17004859
TI  - Diabetes insipidus.
AB  - Water balance is precisely regulated by vasopressin, thirst and the kidneys;
      plasma osmolality is maintained within a narrow range, despite large variations
      in normal water intake and loss. Disruption of these finely balanced mechanisms
      is common, however, and can be precipitated by various disease states. Diabetes
      insipidus is a disease process with several underlying pathogenic mechanisms--all
      ultimately resulting in excretion of large volumes of dilute urine. This review
      will discuss the pathophysiology, diagnosis and treatment of diabetes insipidus,
      with emphasis on disorders of osmoregulation following neurosurgery of the
      pituitary and hypothalamus.

PMID- 17004860
TI  - Transsphenoidal microsurgery: past, present and future.
AB  - In this report, we first describe the history of transsphenoidal surgery. We
      further elaborate on three fundamental surgical anatomy principles of
      transsphenoidal surgery for pituitary adenomas. First, the pituitary gland and,
      therefore, pituitary adenomas are extra-arachnoid structures, therefore the
      operation should be executed without penetration into the subarachnoid space.
      Second, the pituitary gland and, therefore, pituitary adenomas are midline
      structures, thus, veering off midline can result in potentially serious
      complications. Third, pituitary adenomas commence inside the pituitary gland,
      which distends around them as they grow. Thus, pituitary macroadenomas are
      surrounded on their surface by a layer of attenuated residual normal anterior
      pituitary. The operative technique for pituitary micro- and macroadenomas is
      described in detail. Finally, we discuss the likely future treatment methods for
      pituitary adenomas.

PMID- 17004861
TI  - Role of craniotomy in the management of pituitary adenomas and sellar/parasellar
      tumors.
AB  - The transphenoidal procedure has become the preferred approach in the surgical
      management of sellar/parasellar tumors. Nevertheless, specific indications remain
      for the transcranial approach and the objective of this review is to evaluate the
      available data on outcomes following transcranial or transphenoidal approaches to
      sellar/parasellar tumors. We assess the indications used for each approach and
      parameters that favor one over the other. Factors such as tumor size, consistency
      and configuration are important variables in choosing the transcranial approach.
      Other important considerations include persistent visual loss after incomplete
      decompression via the transphenoidal route, ectatic midline carotid arteries, co
      existent intracranial aneurysms and sphenoid sinusitis. We review the data on
      visual and endocrinological outcomes following the transcranial or transphenoidal
      approach and provide an argument that, while there appears to be a trend towards
      greater visual improvement after transcranial surgery for large-to-giant
      pituitary adenomas, this benefit is offset by a greater risk of postoperative
      pituitary dysfunction. There is no difference in the rate of recurrence between
      the two procedures in the published literature. Overall, craniotomies will
      continue to play a role in the management of patients with sellar/parasellar
      tumors, although patient selection and careful preoperative evaluation are key
      elements in choosing the most appropriate approach.

PMID- 17004862
TI  - Craniopharyngiomas: an update.
AB  - Craniopharyngiomas have been challenging practitioners for over 100 years. These
      benign cystic tumors are thought to be a part of a continuum of ectodermal cystic
      lesions found in the suprasellar region. They are rare tumors found in both the
      adult and pediatric populations. Patients most often present with findings
      associated with ventricular outflow obstruction causing hydrocephalus, optic
      chiasm compression resulting in visual dysfunction or hypothalamic/pituitary
      compression leading to endocrinopathy. The mainstay of treatment involves a
      combination of radical or limited surgery followed by radiotherapy. Other
      adjunctive strategies include cyst fenestration, Ommaya catheter implantation and
      brachytherapy. Patients in general have high long-term survival but can have
      significant tumor- and treatment-associated morbidity requiring a lifetime of
      medical and psychological management.

PMID- 17004863
TI  - Evolving use of radiotherapy and radiosurgery in the treatment of pituitary
      adenomas.
AB  - Conventional external beam radiotherapy has been historically employed in the
      treatment of pituitary adenomas either as a single modality or following
      suboptimal surgical resection. However, with the widespread adoption of the trans
      sphenoidal surgery, the role of radiation therapy has been limited to cases
      deemed resectable or in those with subtotal resections. Advances in radiotherapy
      have improved the dose distribution to the pituitary mass while minimizing the
      volume of normal tissues receiving doses of radiation near or exceeding their
      inherent tolerances, permitting radiation oncologists to migrate from simple 2D
      radiation planning to 3D planning. Fractionated radiosurgery, linear
      accelerator/gamma source-based radiosurgery, or image-guided/intensity-modulated
      radiotherapy is now commonly employed. Long-term follow-up data demonstrate
      excellent progression-free survival and local control along with few
      complications for all radiation treatment modalities whether employed as
      monotherapy or following subtotal resection.

PMID- 17004864
TI  - Curative resection of rectal carcinoid tumors with transanal endoscopic
      microsurgery.
AB  - BACKGROUND: Transanal endoscopic microsurgery is a minimally invasive technique
      for local resection of rectal tumors. Its place needs to be defined for resection
      of carcinoid tumors of the rectum. MATERIALS AND METHODS: From 1998 to 2004,
      rectal carcinoid tumors were diagnosed in 5 patients. The diagnosis was suggested
      at biopsy in all patients. All tumors were resected full thickness with transanal
      endoscopic microsurgery. Data were obtained retrospectively from a review of
      hospital charts. RESULTS: At the time of operation all tumors were small without
      clinical or biochemical signs of metastasis. All resected tumors were highly
      differentiated and had free margins without invasion into the submucosa.
      Operative times ranged from 15 to 35 minutes. Hospital stays ranged from 2 to 4
      days. No morbidity or mortality was observed. Follow-up ranged from 3 to 75
      months. No recurrences were observed. CONCLUSION: Transanal endoscopic
      microsurgery is an excellent technique for removal of carcinoid tumors of the
      rectum and even the distal part of the sigmoid, if the diameter is <1 cm without
      invasion of the rectal wall.

PMID- 17004865
TI  - Mesh fixation devices and formation of intraperitoneal adhesions.
AB  - PURPOSE: To investigate the effect of mesh fixation devices on the formation of
      intra-abdominal adhesions. MATERIALS AND METHODS: Fourteen New Zealand rabbits
      were used. In seven animals, nickel-titanium (nitinol) anchors (group 1) and
      titanium tacks (group 2) were applied by laparoscopy on the right and left sides
      of the abdomen, respectively. In the remaining seven rabbits, the same devices
      were applied on prosthetic meshes (groups 3 and 4, respectively). On day 30, the
      rabbits were sacrificed and macroscopic adhesion scoring was performed. All the
      specimens were assessed by scanning electron microscopy (SEM). RESULTS: All
      parameters of adhesion except extension were significantly higher in group 4 than
      group 3 (P < 0.05). Comparisons of group 1 vs. group 2 were not statistically
      significant (P > 0.05). All the comparisons between a nonmesh group and a mesh
      group resulted in significant differences. SEM results revealed that the
      mesothelial cell layer and connective tissue intensively covered the tacks in
      group 2 whereas no similar findings were observed in group 1. Comparable
      appearances were encountered in groups 3 and 4. CONCLUSION: The nitinol anchor is
      associated with an acceptable level of adhesion formation and its intraperitoneal
      use can be considered safe in this regard.

PMID- 17004866
TI  - Mentoring console improves collaboration and teaching in surgical robotics.
AB  - BACKGROUND: One of the most significant limitations of surgical robots has been
      their inability to allow multiple surgeons and surgeons-in-training to engage in
      collaborative control of robotic surgical instruments. We report the initial
      experience with a novel two-headed da Vinci surgical robot that has two
      collaborative modes: the "swap" mode allows two surgeons to simultaneously
      operate and actively swap control of the robot's four arms, and the "nudge" mode
      allows them to share control of two of the robot's arms. MATERIALS AND METHODS:
      The utility of the mentoring console operating in its two collaborative modes was
      evaluated through a combination of dry laboratory exercises and animal laboratory
      surgery. The results from surgeon-resident collaborative performance of complex
      three-handed surgical tasks were compared to results from single-surgeon and
      single-resident performance. Statistical significance was determined using
      Student's t-test. RESULTS: Collaborative surgeon-resident swap control reduced
      the time to completion of complex three-handed surgical tasks by 25% compared to
      single-surgeon operation of a four-armed da Vinci (P < 0.01) and by 34% compared
      to single-resident operation (P < 0.001). While swap mode was found to be most
      helpful during parts of surgical procedures that require multiple hands (such as
      isolation and division of vessels), nudge mode was particularly useful for
      guiding a resident's hands during crucially precise steps of an operation (such
      as proper placement of stitches). CONCLUSION: The da Vinci mentoring console
      greatly facilitates surgeon collaboration during robotic surgery and improves the
      performance of complex surgical tasks. The mentoring console has the potential to
      improve resident participation in surgical robotics cases, enhance resident
      education in surgical training programs engaged in surgical robotics, and improve
      patient safety during robotic surgery.

PMID- 17004867
TI  - Laparoscopic surgery for benign lesions of the pancreas.
AB  - BACKGROUND: Minimally invasive pancreatic surgery, although known to be feasible
      and safe, is still not considered a standard procedure. We report our experience
      with laparoscopic pancreatic surgery in a retrospective case series. MATERIALS
      AND METHODS: Fifteen consecutive patients (3 male, 12 female) underwent primarily
      laparoscopic pancreatic surgery from February 2000 to June 2005. Histologically
      confirmed diagnoses were: neuroendocrine pancreatic tumors (n = 11), adult
      nesidioblastosis (n = 1), serous cystadenoma (n = 1), and pseudocysts due to
      chronic pancreatitis (n = 2). RESULTS: Enucleation (n = 3) or left pancreatic
      resection with spleen preservation (n = 6) was performed laparoscopically in 9
      patients. The mean (+/-standard deviation) operative time was 173 +/- 48 minutes
      (range, 120-250 minutes) and the mean postoperative hospital stay was 5.5 +/- 1.2
      days (range, 5-8 days) for the laparoscopic cases. Conversion to open surgery was
      necessary in 6 patients because of: closeness of the lesion to the
      portal/mesenteric vein (n = 3), inadequate intraoperative tumor localization (n =
      2), or stapler device dysfunction (n = 1). In these patients, open enucleation (n
      = 1), middle segment pancreatectomy (n = 2), left pancreatic resection (n = 2),
      and pylorus-preserving Whipple resection (n = 1) were performed. The mean
      operative time was 268 +/- 74 minutes (range, 150-360 minutes) with a mean
      postoperative hospital stay of 8 +/- 2 days (range, 6-10 days). Both operative
      time and hospital stay were significantly longer in patients with secondary open
      surgery compared to patients with successful laparoscopic operations. CONCLUSION:
      Laparoscopic enucleation or distal pancreatectomy with spleen preservation for
      benign lesions located in the body or tail of the pancreas can be performed
      safely, with all the potential benefits of minimally invasive surgery.
      Preoperative tumor localization is of utmost importance to limit pancreatic
      mobilization and to avoid blind pancreatic resection and conversion to open
      surgery.

PMID- 17004868
TI  - Patients with pancreatic adenocarcinoma benefit from staging laparoscopy.
AB  - BACKGROUND: Unnecessary laparotomy in patients with advanced pancreatic cancer
      may both compromise the quality of life and delay the initiation of more
      appropriate therapy. Very often, peritoneal small liver metastases and true local
      status cannot be fully determined without surgery. Laparoscopy may spare
      laparotomy and decrease morbidity for patients with nonresectable advanced
      disease. The aim of this study was to determine the impact of laparoscopy in
      patients with potentially resectable adenocarcinoma of the pancreas. MATERIALS
      AND METHODS: We reviewed the records of patients undergoing pancreatic surgery at
      the University of Nebraska Medical Center from October 2001 to April 2005. A
      total of 59 patients were included in the study. All patients were staged
      radiographically with a high resolution helical computed tomography scan and
      their tumors were considered resectable. Thirty-seven patients underwent staging
      laparoscopy while 22 proceeded directly to laparotomy. RESULTS: Of the 37
      patients who underwent laparoscopic staging, 9 (24.3%) were detected to have
      metastatic disease or advanced tumor; the remaining 28 (75.7%) patients with
      negative laparoscopy proceeded to laparotomy. Of those, 24 patients (85.7%)
      underwent pancreatic resection with curative intent, while 4 patients had
      metastatic or locally advanced disease at subsequent laparotomy which was missed
      on staging laparoscopy (false negative rate of 14.3%). Of the 22 patients who
      proceeded directly to laparotomy, 16 (72.7%) received curative Whipple resection
      and 6 (27.3%) were found to have advanced disease and received bypass procedures
      or biopsy alone. CONCLUSION: These findings suggest that staging laparoscopy is
      beneficial in a significant proportion of patients deemed resectable by routine
      noninvasive preoperative studies. We plan to add intraoperative laparoscopic
      ultrasound to our staging protocol in order to decrease the false negative rate.

PMID- 17004869
TI  - Effect of fluid irrigation on core body temperature during laparoscopic common
      bile duct exploration.
AB  - BACKGROUND: Laparoscopic common bile duct exploration uses large volumes of
      intraperitoneal irrigation fluid. Much of this fluid crosses the peritoneal
      cavity. This study was performed to examine its effect on core body temperature.
      MATERIALS AND METHODS: Ten patients undergoing laparoscopic bile duct exploration
      were studied. Core temperature was measured intraoperatively. Patients were
      covered with a warming blanket. The volume of fluid irrigated, carbon dioxide
      used, and intravenous fluid infused were recorded. Ten patients having
      cholecystectomy alone were studied as a control group. RESULTS: There was a small
      but significant rise in core temperature in both the study (P = 0.010) and
      control (P = 0.002) groups. There was no significant difference in the change in
      core temperature between the groups (P = 0.706).The mean volume of irrigation
      fluid used was 2640 mL in the study group and 915 mL in the control group. Mean
      gas volume used was 162.9 L and 73.3 L and the volume of intravenous fluid
      infused was 1620 mL and 1190 mL in the study and control groups, respectively.
      CONCLUSION: The use of large volumes of irrigation fluid during laparoscopic bile
      duct exploration does not cause a fall in core temperature.

PMID- 17004870
TI  - Laparoscopic management of cholecystoenteric fistulas.
AB  - BACKGROUND: Cholecystoenteric fistulas are a rare complication of gallstone
      disease and affect 3-5% of patients with cholelithiasis. Most fistulas are
      diagnosed intraoperatively. MATERIALS AND METHODS: Between January 1997 and June
      2003, 12428 patients underwent laparoscopic cholecystectomy at our department.
      Cholecystoenteric fistula was diagnosed intraoperatively and treated in 63
      patients: 45 patients (71.4%) had cholecystoduodenal fistulas, while
      cholecystogastric and cholecystocolic fistulas were found in 9 patients (14.3%)
      and 4 patients (6.3%), respectively; and 5 patients (7.9%) were found to have
      Mirizzi syndrome type I along with a cholecytoenteric fistula. The operation
      could be completed laparoscopically in 59 patients. An endostapler was used in 47
      patients to transect the fistula and in 12 patients the defect in the bowel was
      repaired with intracorporeal sutures. RESULTS: Major morbidity occurred in 3
      patients (4.76%). One patient developed a loculated subdiaphragmatic collection
      which was treated by ultrasound guided aspiration and antibiotic therapy.
      Prolonged biliary drainage occurred in 2 patients. In addition, 7 patients
      (11.11%) had minor postoperative complications. The mean postoperative hospital
      stay was 5.2 days. All the patients are asymptomatic at a mean follow-up of 2.4
      years. CONCLUSION: Cholecystoenteric fistula is a difficult problem usually
      diagnosed intraoperatively. A high degree of suspicion at operation is mandatory.
      A stapled cholecystofistulectomy may be the procedure of choice since it avoids
      contamination of the peritoneal cavity. Complete laparoscopic management of
      cholecystoenteric fistulas is possible in well-equipped high-volume centers.

PMID- 17004871
TI  - Robot-assisted cortical-sparing adrenalectomy in a patient with Von Hippel-Lindau
      disease and bilateral pheochromocytomas separated by 9 years.
AB  - Von Hippel-Lindau disease is a heritable syndrome that confers an increased risk
      of developing various benign and malignant tumors to those with a germline
      mutation of the tumor suppressor gene. We present a case of a male patient who
      initially presented at age 9 with headaches, fevers, and fatigue. He was found to
      have a left pheochromocytoma which was successfully managed with open total
      adrenalectomy. He presented again at age 18 with a second pheochromocytoma in the
      right adrenal gland. DNA analysis revealed a de novo Val84Leu mutation in the Von
      Hippel-Lindau gene, not seen in either parent. The challenge presented was that
      of balancing the obvious benefits of cortical- sparing adrenalectomy with the
      risk of tumor recurrence in spared tissue. Ultimately, management consisted of a
      robot-assisted laparoscopic partial right adrenalectomy with successful
      preservation of adrenocortical function.

PMID- 17004872
TI  - Laparoscopic resection of an adrenal pseudocyst.
AB  - Adrenal pseudocysts are rare cystic lesions surrounded by a layer of fibrous
      tissue that lacks epithelial or endothelial cells. Patients with adrenal
      pseudocysts may be asymptomatic or present with abdominal pain or other
      gastrointestinal symptoms. We present the case of a morbidly obese 41- year-old
      woman who presented with left flank pain. A computed tomography scan of the
      abdomen and pelvis discovered an 8-cm adrenal lesion. The lesion was hormonally
      inactive and a transperitoneal laparoscopic left adrenalectomy was performed to
      exclude malignancy. Pathology discerned multiple pseudocysts with and without
      calcifications. The patient was discharged on postoperative day 2. She has been
      asymptomatic in terms of left flank pain for 12 months. We report this case in
      detail and briefly review the literature regarding adrenal pseudocysts.

PMID- 17004873
TI  - Postcholecystectomy syndrome in the laparoscopic era.
AB  - sWe describe the management of a cystic duct remnant calculus in a 45-year-old
      male patient who had undergone a laparoscopic cholecystectomy and re-presented
      with abdominal pain and jaundice. Magnetic resonance cholangiopancreatography was
      utilized to confirm the diagnosis of an impacted calculus within the remnant
      cystic duct along with several small retained common bile duct stones. Four
      sequential endoscopic procedures successfully removed all retained common bile
      duct calculi to alleviate the biliary obstruction; however, we were unable to
      treat the cystic duct remnant calculus endoscopically. The patient finally
      underwent successful laparoscopic excision of a 2.5-cm cystic duct remnant
      containing its impacted calculus. It remains unclear if cystic duct remnant
      calculi may become more prevalent as a cause of postcholecystectomy syndrome in
      future due to the large numbers of laparoscopic cholecystectomies performed in
      the past 2 decades.

PMID- 17004874
TI  - Simultaneous laparoscopic resection of rectal cancer and liver metastasis.
AB  - Simultaneous resection of colorectal tumor and liver metastasis has been
      advocated because of the benefits of avoiding a second operation, reduced
      morbidity, shorter treatment time, and similar outcomes. We report a case of
      simultaneous laparoscopic resection. The operative time was 350 minutes and the
      estimated blood loss was 500 mL. The patient required parenteral analgesia for
      less than 48 hours. Flatus was passed on postoperative day 3, and a solid diet
      was resumed on postoperative day 5. He was fully mobile on postoperative day 4
      and was discharged 3 days later. With the advance of laparoscopic technology and
      technique, simultaneous resection becomes an attractive option.

PMID- 17004875
TI  - Video-assisted thoracoscopic excision of intradiaphragmatic bronchogenic cysts:
      two cases.
AB  - We report two cases of bronchogenic cyst in the diaphragm. Case 1 was a female
      patient with hepatocellular carcinoma. Computed tomography showed a tumor in the
      right lower lung and metastasis was suspected initially because of underlying
      disease and imaging findings. Case 2 was a female patient who presented with
      prolonged intermittent cough. Computed tomography showed a tumor in the left
      lower lung. Both tumors were excised by video-assisted thoracoscopic surgery, and
      the diagnosis was confirmed by histopathology.

PMID- 17004876
TI  - Intrabiliary rupture of a large liver echinococcal cyst in an adolescent managed
      with endoscopic sphincterotomy and albendazole.
AB  - We report the case of a 17-year-old male with a rupture into the biliary tract.
      The patient was urgently admitted to the surgical department with the clinical
      diagnosis of cholangitis. Modern imaging techniques and specific serologic tests
      established the diagnosis of intrabiliary rupture of a liver hydatid cyst due to
      E. granulosus. Despite the fact that surgery remains the cornerstone of
      treatment, conservative management was preferred, due to the location of the
      echinococcal cyst in the right lobe of the liver adjacent to the inferior vena
      cava and the age of the patient. Endoscopic sphincterotomy was performed with
      subsequent evacuation of the biliary tree, followed by a sixcycle treatment with
      albendazole. At one-year follow-up, the patient is in good health, with no
      radiologic or serologic evidence of relapse.

PMID- 17004877
TI  - A novel instrument and technique for using Seprafilm hyaluronic
      acid/carboxymethylcellulose membrane during laparoscopic myomectomy.
AB  - Myomectomy is associated with the development of adhesions, and even when the
      patient is operated on laparoscopically, postoperative adhesions can often occur.
      Seprafilm is an effective and highly safe barrier to postoperative adhesions.
      However, it is vulnerable to tears and difficult to handle. We developed a device
      to introduce Seprafilm into the abdominal cavity during the laparoscopic
      procedure. Seprafilm is divided into 6 pieces and the pieces are rolled and
      inserted into the purpose-built introducer to be guided into the abdominal
      cavity. The inner syringe is pushed in and Seprafilm is applied onto the uterine
      wound with two grasping forceps. Of 117 patients in our study, we were able to
      use Seprafilm on 114 patients (97.4%). In total, 221 pieces of Seprafilm were
      used, and 87 pieces were damaged during the operation. Of these 87 pieces, 58
      were damaged when inserted into the introducer, though this kind of loss tended
      to decrease with training, and 29 pieces were damaged during application to the
      wound. Seprafilm can be used safely and efficiently during laparoscopic surgery.

PMID- 17004878
TI  - Effect of visual feedback on surgical performance using the da Vinci surgical
      system.
AB  - BACKGROUND: Robotic surgical systems quantify human movements in terms of
      position, velocity, and time span. This information can be used to objectively
      assess surgical skill. The aim of this study was to test the effects of three
      dimensional vs. two-dimensional visualization on performance using the da Vinci
      Surgical System (Intuitive Surgical, Sunnyvale, CA). MATERIALS AND METHODS: The
      movements of novice and expert surgeons were recorded using the da Vinci Surgical
      System for a two-handed task in two visual environments (two-dimensional and
      three-dimensional). Data were analyzed to investigate the effect of visual
      feedback on performance. RESULTS: Velocities and task completion times were
      significantly different for novices and experts (P < 0.05) for all velocity
      parameters in both visual conditions. Additionally, there was a significant
      difference between two-dimensional and three-dimensional times for novices (P <
      0.05). Novices were idle significantly longer in two-dimensional than in three
      dimensional visual input (P = 0.037), and overall, novices were idle longer than
      experts for both visual conditions (P = 0.001). CONCLUSION: Three-dimensional
      visual input allows novice surgeons to perform tasks with higher velocities, less
      idle time, and greater economy of motion. However, three-dimensional visual input
      provides no significant enhancement of performance for expert surgeons.

PMID- 17004879
TI  - Thoracoscopy in Chest Wall Ewing's Sarcoma.
AB  - Minimally invasive surgery has a role in planning the resection of malignant
      chest wall tumors in the pediatric population. We studied the role of
      thoracoscopy in both the diagnosis and definitive surgery of chest wall Ewing's
      sarcoma tumors.

PMID- 17004880
TI  - Percutaneous internal ring suturing: a simple minimally invasive technique for
      inguinal hernia repair in children.
AB  - BACKGROUND: Laparoscopic herniorrhaphy in pediatric surgery is usually performed
      through three ports in the abdominal wall with intraperitoneal suturing. Our
      technique of percutaneous internal ring suturing (PIRS) requires only one
      umbilical port and needle puncture point. We describe the technique and evaluate
      the efficacy of percutaneous internal ring suturing for inguinal hernia repair in
      children. MATERIALS AND METHODS: We performed percutaneous internal ring suturing
      on 106 children (ages 28 days-14.5 years) with 140 hernias. The procedures were
      performed under general endotracheal anesthesia. Pneumoperitoneum was established
      with an open technique. Under laparoscopic-guided vision an 18-gauge injection
      needle with a nonabsorbable thread inside the barrel of the needle was placed
      through the abdominal wall into the peritoneal cavity. By moving the injection
      needle, the thread passed under the peritoneum around the entrance into the
      hernia sac. The knot was tightened from outside and placed in the subcutaneous
      space. The contralateral open inguinal ring was closed in the same procedure.
      RESULTS: The average operative time was 19 minutes for unilateral and 24 minutes
      for bilateral hernias. Follow-up ranged between 18 and 29 months. Cosmetic
      results are excellent with almost invisible scars. There were 3 cases of
      intraoperative complication: incidental puncture of the iliac vein that required
      no treatment. There were 4 cases of postoperative complications: one case of
      ileus adhesion with bowel strangulation, and hernia recurrence in 3 boys, one of
      whom was reoperated with percutaneous internal ring suturing. In 5 boys,
      transient hydroceles were observed that disappeared spontaneously after 3 to 5
      months. CONCLUSION: The percutaneous internal ring suturing method seems to be a
      simple and effective minimally invasive procedure with excellent cosmetic
      results. The rate of complications is comparable to other laparoscopic techniques
      of inguinal hernia repair in children. According to our experience, percutaneous
      internal ring suturing should be considered as a treatment alternative.

PMID- 17004881
TI  - Thoracoscopic pericardiectomy for purulent pericarditis: experience with 21
      cases.
AB  - PURPOSE: We present our experience in performing thoracoscopic pericardiectomy
      for purulent pericarditis in 21 children. MATERIALS AND METHODS: Pericardiectomy
      was carried out using one optical trocar and two operating trocars. Pleural
      insufflation with carbon dioxide was maintained at 2-4 mm Hg. Anterior
      pericardiectomy was performed from the left phrenic nerve to the right border of
      the sternum to free the anterior part of the heart, notably the cardiac apex and
      the original area of the great vessels. Purulent debris was removed prior to
      detaching the epicardial peel. RESULTS: This study included 21 patients. Their
      mean age was 8 years. The time from onset of the disease to surgery ranged from 4
      to 34 days (average, 15.2 days). Operative times ranged from 50 to 180 minutes
      (average, 100 minutes). There were no intraoperative or postoperative
      complications. All symptoms of cardiac tamponade disappeared immediately
      postoperatively. Follow-up ranged from 4 to 15 months and showed normal clinical
      manifestations, echocardiographs, and chest x-rays in all children. CONCLUSION:
      Thoracoscopic pericardiectomy with removal of a generous amount of the
      pericardium is feasible and safe for purulent pericarditis.

PMID- 17004882
TI  - LigaSure in laparoscopic transperitoneal heminephroureterectomy in children: a
      comparative study.
AB  - BACKGROUND: This study was conducted to evaluate the feasibility of using the
      LigaSure vessel sealing system (Valleylab, Boulder, CO) in laparoscopic
      transperitoneal vs. open retroperitoneal heminephroureterectomy in children.
      MATERIALS AND METHODS: Seven consecutive patients with impaired renal duplex
      systems underwent laparoscopic heminephroureterectomies using LigaSure between
      April 2003 and April 2005. The operative time, complications, and hospital stay
      were analyzed prospectively. The data of 7 consecutive patients who had undergone
      open retroperitoneal heminephroureterectomy from 2001 to 2003 were analyzed for
      comparison purposes. The mean ages, underlying disease, and location of the
      affected kidney pole were not significantly different between these groups.
      RESULTS: There were no intraoperative complications during laparoscopic
      heminephroureterectomy and all procedures were completed laparoscopically. The
      mean operative time of 144 minutes (range, 90-210 minutes) for laparoscopic
      heminephroureterectomy was somewhat longer than in open heminephroureterectomy
      mean time 110 minutes (range, 60-165 minutes) (P = 0.5). Complications of open
      retroperitoneal heminephroureterectomy included bleeding of the surface of the
      remaining kidney pole in one patient, requiring extensive hemostatic suturing.
      Postoperative recovery was uneventful in all laparoscopic procedures, whereas
      intermittent retention of urine was noticed in one patient undergoing the open
      procedure. CONCLUSION: Laparoscopic heminephroureterectomy using LigaSure is
      feasible in children and has a similar operative time compared to conventional
      heminephroureterectomy.

PMID- 17004883
TI  - Thoracoscopic resection of foregut duplication cysts.
AB  - BACKGROUND: Foregut duplications are rare entities that include both esophageal
      and bronchogenic cysts. The diagnosis of foregut duplication cyst is made most
      often from an incidental finding on chest radiograph, or due to respiratory
      compromise due to mass effect or infection. Treatment consists of complete
      resection. Recurrences are associated with incomplete resection. Six cases of
      foregut duplication cysts are presented that were resected thoracoscopically.
      MATERIALS AND METHODS: From May 1998 to April 2003, six patients underwent
      thoracoscopy for resection of foregut duplication cyst. One patient required
      conversion to open thoracotomy due to esophageal perforation. The distribution of
      cysts was 4 on the left and 2 on the right; all procedures were performed with
      three or four ports. Single lung ventilation was used in three patients. The
      masses were removed via a port site after intrathoracic decompression. Chest
      tubes were placed in all patients, and most were removed within 12 hours.
      RESULTS: Five of six cases underwent successful thoracoscopic resection.
      Pathology demonstrated esophageal duplication cyst in three patients and
      bronchogenic cyst in the other three patients. Average hospital stay was 5.5
      days. Complications included aspiration pneumonia and chest tube dislodgment.
      There were no deaths, and no recurrences. CONCLUSION: Thoracoscopic resection is
      a safe and effective method of treating foregut duplications. Outcomes have been
      good with little short-term morbidity and no mortality. Morbidity and cosmesis
      are improved by avoiding thoracotomy. Thoracoscopic resection should be
      considered the first-line therapy for these benign masses.

PMID- 17004884
TI  - Total laparoscopic excision of retroperitoneal cystic lymphangioma.
AB  - Retroperitoneal cystic lymphangioma is a rare benign tumor of the retroperitoneal
      lymphatics that usually manifests in infancy. If surgical excision is used in
      treatment, it needs to be as complete as possible to reduce the risk of
      recurrence. Two pediatric patients, an 18-month-old girl and a 4-yearold boy,
      underwent laparoscopic excision of symptomatic retroperitoneal cystic
      lymphangiomas. Macroscopically, the resection was complete in both cases. The
      postoperative course in both cases was uneventful. Both children remained
      asymptomatic and no recurrence was observed at 18-month follow-up. Complete
      laparoscopic excision should be considered as a therapeutic option to treat
      retroperitoneal cystic lymphangioma.

PMID- 17004885
TI  - Bilateral laparoscopic transperitoneal adrenalectomy in three children.
AB  - BACKGROUND: This study focuses on the clinical presentation, surgical technique,
      and results of bilateral laparoscopic adrenalectomy in three girls aged 6, 13,
      and 14. MATERIALS AND METHODS: This retrospective study included two girls with
      bilateral tumors (pheochromocytomas in one case, recurrent leiomyosarcomas in the
      other case) and a girl with micronodular hyperplasia associated with Cushing's
      syndrome. RESULTS: Six transperitoneal laparoscopic adrenalectomies were
      performed with no conversions. The average operative time was 137 minutes (range
      125-148); the mean estimated blood loss was 75 mL; the mean size of the adrenal
      lesions was 8 cm (range, 0.5-9); and the mean length of hospital stay was 3 days
      (range, 2-4). Resolution of clinical and biochemical parameters of adrenal
      hyperfunction was accomplished in the patients with adrenocortical hyperplasia
      and pheochromocytoma. No tumor recurrence has been so far found in the case of
      the leiomyosarcomas. CONCLUSION: Bilateral laparoscopic adrenalectomy can be
      performed safely and effectively with a shorter hospital stay, minimal blood
      loss, and excellent functional outcome in the pediatric population.

PMID- 17004886
TI  - Obstruction due to rectal cuff after laparoscopy-assisted transanal endorectal
      pull-through for Hirschsprung's disease.
AB  - We report a case of persistent obstruction after laparoscopy-assisted transanal
      endorectal pullthrough for Hirschsprung's disease in a 4-week-old boy with biopsy
      proven HD. Before pull-through, the posterior rectal cuff was split along its
      entire length cranially, starting from the dentate line. Initial recovery was
      uneventful; however, signs of obstruction developed 3 weeks postoperatively.
      Reoperation through a posterior sagittal approach confirmed a residual rectal
      cuff surrounding the neo-rectum circumferentially. The dorsal side of the
      residual rectal cuff was removed completely. At follow-up 5 years later, he
      defecates 2 to 4 times a day with occasional staining. We hypothesize that the
      persistent postoperative obstruction was caused by a long residual rectal cuff
      that spontaneously reapproximated and/or became folded during pull-through.
      Therefore, a shorter cuff with near-total posterior excision should be strongly
      considered during laparoscopy-assisted transanal endorectal pull-through for
      Hirschsprung's disease.

PMID- 17004887
TI  - Transumbilical approach to intraoperative enteroscopy in a child with
      intussusception and Peutz-Jeghers syndrome.
AB  - Intraoperative enteroscopy has been known to reduce reoperation rates in
      complicated Peutz- Jeghers polyposis. It is usually performed during a
      laparotomy. This case report illustrates the feasibility of performing
      intraoperative transenterotomy enteroscopy together with extracorporeal ileal
      resection using the transumbilical approach after successfully reducing an
      intussusception laparoscopically in a 10-year-old child with Peutz-Jeghers
      syndrome. This technique obviates the need for a laparotomy.

PMID- 17004888
TI  - Thoracoscopic ligation of the thoracic duct in a child with spontaneous
      chylothorax.
AB  - We report a case of a 2-year old girl with a spontaneous chylothorax who
      presented with respiratory distress. The management of this condition, which
      included thoracic duct ligation using a thoracoscopic technique, is discussed,
      and we review the literature on chylothorax.

PMID- 17004889
TI  - trans-10,cis-12 conjugated linoleic acid inhibits the G1-S cell cycle progression
      in DU145 human prostate carcinoma cells.
AB  - Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of
      linoleic acid, and has evidenced anti-cancer activities in experimental animal
      cancer models and in vitro studies. The two predominant isomers of CLA are cis
      9,trans-11 CLA (c9t11) and trans-10,cis-12 CLA (t10c12). The present study was
      performed to study the effect of the individual CLA isomers on DU145 cell growth.
      The cells were incubated in serum-free medium with different concentrations of
      the fatty acids. Treatment of cells with t10c12 (at 2.5-10 micromol/L) resulted
      in a dose-dependent reduction in the numbers of viable cells, whereas c9t11 CLA
      at a concentration of 5 micromol/L slightly increased viable cell numbers at 3
      days (P < .05). DNA flow cytometric analysis revealed that the treatment of DU145
      cells with t10c12 for 24 hours induced a small but significant increase in the
      number of cells in the G1 phase, accompanied by a complementary decrease in cells
      in the S phase. c9t, however, had no effect on cell cycle progression. To
      determine the molecular mechanisms underlying t10c12-induced G1 arrest, the
      levels of cell cycle regulatory proteins were estimated by western blot analyses.
      t10c12 induced a marked increase in p21(CIP1/WAF1) protein levels in a dose
      dependent manner. p27(KIP1) was not affected by t10c12. t10c12 moderately
      decreased cyclin A and cyclin D1 protein levels (P > .05). However, t10c12 did
      not affect the expression of cyclin-dependent kinase (CDK) 2, CDK4, or cyclin E.
      t10c12 increased p21(CIP1/WAF1) bound to CDK2 and attenuated CDK2 activity. These
      results indicate that t10c12-induced p21(CIP1/WAF1) binds to CDK, and inhibits
      the activity of this enzyme, which results in the observed decrease in the G1-S
      progression in DU145 cells.

PMID- 17004890
TI  - Inhibition of pro-angiogenic factors by a lipid-rich shark extract.
AB  - This study aimed to determine whether a shark muscle oil-olive oil mixture
      influences activators of human angiogenesis. The mixture completely abolished the
      stimulation induced by vascular endothelial growth factor (VEGF), fibroblast
      growth factor-2, transforming growth factor-beta, and platelet-derived growth
      factor. This suggests that it may compete with these growth factors for their
      binding sites on the endothelial cell surface either by binding to the growth
      factor or by blocking the actual receptor. The possibility of the oil binding to
      the VEGF receptor was studied through the use of soluble forms of the receptors
      (VEGF-R1 and VEGF-R2). It was found that the shark oil-olive oil inhibited the
      formation of the complexes of VEGF with both of the receptors. This could have
      been because the oil bound to either the VEGF or the receptor or both. To
      determine which is possible, the shark oil-olive oil was mixed with the
      receptors. The molecular size of the receptors increased, and these larger forms
      of the receptor had reduced capacity for complexing with VEGF. Therefore, one
      mode of potential anti-angiogenic action of the shark muscle oil-olive oil is the
      inhibition of the activity of a number of stimulatory molecules, including VEGF.
      This study demonstrates that the blend of shark and olive oils antagonizes VEGF
      activity by binding to at least two receptors for the factor, thereby inhibiting
      the activation by the growth factor.

PMID- 17004891
TI  - Isomer-specific effect of conjugated linoleic acid on inflammatory adipokines
      associated with fat accumulation in 3T3-L1 adipocytes.
AB  - The purpose of this study was to examine the isomer-specific effect of conjugated
      linoleic acid (CLA) on inflammatory markers associated with fat accumulation in
      cultures of differentiating 3T3-L1 adipocytes. trans-10,cis-12 CLA (t10c12 CLA)
      reduced leptin secretion and fat accumulation. Linoleic acid (LA) and cis-9,trans
      11 CLA (c9t11 CLA) increased them, but not significantly. t10c12 CLA and LA
      showed similar effects on mRNA expression of inflammatory markers. t10c12 CLA and
      LA tended to up-regulate the mRNA levels of inflammatory cytokines such as
      interleukin (IL)-6 (not significantly), tumor necrosis factor (TNF)-alpha, and C
      reactive protein (CRP) with no significant change in the secretion of
      adiponectin, an anti-inflammatory adipokine. However, c9t11 CLA induced no
      significant change in the mRNA expression of IL-6, TNF-alpha, or CRP, but
      significantly increased adiponectin secretion. In conclusion, CLA exerted isomer
      specific effects on fat accumulation and mRNA expression of inflammatory markers
      in 3T3-L1 adipocytes. t10c12 CLA up-regulated inflammatory markers in spite of
      the decreased fat accumulation, and TNF-alpha might be one of the causal factors.

PMID- 17004892
TI  - Antioxidant and cancer cell proliferation inhibition effect of citrus pectin
      oligosaccharide prepared by irradiation.
AB  - Pectin was dissolved in deionized distilled water (2%, vol/vol) and irradiated at
      20 kGy using a Co-60 gamma ray irradiator. The resulting solution was dialyzed
      and lyophilized. The samples were separated into three groups to estimate their
      antioxidant and cancer cell proliferation effects: non-irradiated (0 kGy),
      irradiated (20 kGy), and dialyzed (20 kGy-F, mol wt <10,000) samples. Antioxidant
      properties of each treatment was tested by a beta-carotene-linoleic acid
      bleaching assay and electron donating ability and compared for antioxidant index,
      which indicated that the activity was higher in the order of 20 kGy-F > 20 kGy >
      0 kGy. Spleen cell survival effect of the irradiated pectin (20 kGy) and dialyzed
      (20 kGy-F) samples was higher than the non-irradiated control (0 kGy). The
      pectins inhibited growth of the cancer cell in the order of 20 kGy- F > 20 kGy >
      0 kGy. The Ames test revealed that none of the fractions was mutagenic, and there
      was no indication of a dose-dependent response for any of the samples. These
      results suggest that a functional pectin oligosaccharide can be produced by
      irradiation for the food industry without any chemical treatment.

PMID- 17004893
TI  - Dietary supplementation of probiotic Bacillus polyfermenticus, Bispan strain,
      modulates natural killer cell and T cell subset populations and immunoglobulin G
      levels in human subjects.
AB  - A probiotic is a viable microbial dietary supplement that has beneficial effects
      such as prevention and treatment of specific gastrointestinal disorders,
      including counteracting gut barrier dysfunction associated with inflammation and
      infection. Probiotic Bacillus polyfermenticus, which is commonly called Bispan
      strain, has been appropriately used for the treatment of long-term intestinal
      disorders. The use of B. polyfermenticus for immune-related chronic intestinal
      disease may be appropriate considering that about 80% of the body's immune system
      is localized in the gastrointestinal tract. The current study aimed to evaluate
      the effect of probiotic B. polyfermenticus on the immune response of human
      subjects through the quantification of immune cell population and serum levels of
      immunoglobulins (Igs). Twenty-five male subjects, 20-35 years of age, were
      randomly assigned to either a control group (n =12) supplemented with a placebo
      or the experimental group (n = 13) supplemented with B. polyfermenticus tablets
      at a dose of 3.1 x 10(8) colony-forming units/day for 8 weeks. Dietary intake
      analyses from 3-day dietary records from three consecutive days including one
      weekend day and two weekdays revealed no significant differences in total energy
      and nutrient intakes between the two groups. The humoral immune response was
      monitored by the number of total B lymphocytes and serum concentrations of IgG,
      IgA, and IgM. To investigate the changes in immune cell populations, percentages
      of total T lymphocytes, CD4+ helper T cells, CD8+ cytotoxic T cells, and CD56+
      natural killer (NK) cells were quantified. The concentration of IgG in the
      experimental group was 12% higher than in the placebo group after 8 weeks of
      Bispan supplementation. Also, the percentages of CD4+ helper T cells,
      CD8+cytotoxic T cells, and CD56+ NK cells in the Bispan strain-supplemented group
      were 32%, 28%, and 35% higher, respectively, compared with the control group.
      Because of a higher increment of the CD4+ T cell subset than CD8+ T cells, the
      ratio of CD4+/CD8+ T cells was greater in the experimental group. This study
      suggests that the supplementation of B. polyfermenticus has a potentially
      positive effect on immune function by enhancing IgG production as well as by
      modulating the number of immune cell population such as CD4+ and CD8+ T cells and
      NK cells.

PMID- 17004894
TI  - Effect of skim milk and dahi (yogurt) on blood glucose, insulin, and lipid
      profile in rats fed with high fructose diet.
AB  - In the present study, the effect of skim milk and the fermented milk product
      named dahi (yogurt) on plasma glucose, insulin, and lipid levels as well as on
      liver glycogen and lipid contents in rats fed with high fructose diet has been
      investigated. Rats were fed with high fructose diet (21%) supplemented with skim
      milk, dahi (10 g/day each), or no milk product (control group) for 6 weeks. After
      6 weeks of high fructose diet administration, the plasma glucose became
      significantly higher in control animals (246 mg/dL), whereas it was lower in skim
      milk (178 mg/dL)- and dahi (143 mg/dL)-fed rats. The glucose tolerance became
      impaired at the third week of feeding of high fructose diet in control animals,
      whereas in skim milk- and dahi-fed animals achievement of glucose intolerance was
      delayed until the fourth and fifth week, respectively. Blood glycosylated
      hemoglobin and plasma insulin were significantly lower in skim milk (10% and 34%,
      respectively)- and dahi (17%, and 48%, respectively)-fed animals than those of
      the control group. Plasma total cholesterol, triglycerides, low-density
      lipoprotein-cholesterol, and very-low-density lipoprotein-cholesterol and blood
      free fatty acids were significantly lower in skim milk (13%, 14%, 14%, 19%, and
      14%, respectively)- and dahi (22%, 33%, 30%, 33%, and 29%, respectively)-fed
      animals as compared with control animals. Moreover, the total cholesterol,
      triglyceride, and glycogen contents in liver tissues were also lower in skim milk
      (55%, 50%, and 36%, respectively)- and dahi (64%, 27%, and 4%, respectively)-fed
      animals as compared with control animals. In contrast, high-density lipoprotein
      cholesterol in plasma was higher in skim milk (14%)- and dahi (29%)-fed animals
      as compared with control animals. These results indicate that skim milk and its
      fermented milk product, dahi, delay the progression of fructose-induced diabetes
      and dyslipidemia in rats and that these may be useful as antidiabetic food
      supplements that can be included in daily meals of the diabetic as well as normal
      population.

PMID- 17004895
TI  - Effects of the aerial parts of Orostachys japonicus and its bioactive component
      on hepatic alcohol-metabolizing enzyme system.
AB  - In the course of screening medicinal plants that modulate hepatic alcohol
      metabolizing enzymes and lipid peroxidation, effects of the methanol extract (ME)
      of Orostachys japonicus and its major bioactive compound, gallic acid (GA), were
      investigated in rats treated with 10% ethanol solution for 6 weeks. The ME and GA
      greatly enhanced the activities of hepatic alcohol dehydrogenase (ADH), the
      microsomal ethanol-oxidizing system (MEOS), and aldehyde dehydrogenase (ALDH) in
      a dose-dependent manner, but had no effect on catalase. The hepatic lipid
      peroxide level increased by ethanol administration was moderately reduced by
      treatment with ME or GA. The results suggest that the detoxification of hepatic
      alcohol by O. japonicus ME under our experimental conditions was due to the
      enhanced activities of the alcohol-oxidizing enzymes, ADH, MEOS, and ALDH. In
      addition, GA may be partly responsible for the effects.

PMID- 17004896
TI  - A water extract of Artemisia capillaris prevents 2,2'-azobis(2-amidinopropane)
      dihydrochloride-induced liver damage in rats.
AB  - A water extract of Artemisia capillaris Thunberg (Compositae) was investigated
      for protective effects against oxidative stress induced by 2,2'-azobis(2
      amidinopropane) dihydrochloride (AAPH) in Sprague-Dawley male rats. Rats were
      orally administered A. capillaris water extract (ACWE; 7.5 g/kg) for 7 days
      before AAPH treatment (60 mg/kg). AAPH intoxication significantly elevated enzyme
      markers of liver injury (glutamic oxaloacetic transaminase and glutamic pyruvic
      transaminase). The pre-administration of ACWE significantly reduced the liver
      damaging effects of AAPH as indicated by the low levels of these enzymes.
      Moreover, the ACWE administration significantly attenuated the accumulation of
      thiobarbituric acid-reactive substances in both plasma and liver tissues compared
      with those of rats administered AAPH alone. Furthermore, ACWE administration
      slightly improved the liver reduced glutathione levels and enhanced the
      production of antioxidant enzymes like catalase. A. capillaris contained 10.1 mg
      of catechin in 100 g of dried sample; the high-performance liquid chromatography
      results showed catechin composition in the ACWE to be 28% (-)-epigallocatechin
      gallate, 49% (-)- epigallocatechin, and 23% other catechins. These observations
      clearly indicate that ACWE contains antioxidant catechins capable of ameliorating
      the AAPH-induced hepatic injury by virtue of its antioxidant activity.

PMID- 17004897
TI  - Sulfation of the isoflavones genistein and daidzein in human and rat liver and
      gastrointestinal tract.
AB  - Phytoestrogens, in particular the isoflavone aglycones genistein and daidzein,
      are thought to be the bioactive components of soy. Like estrogens, isoflavones
      can be sulfur-conjugated. However, although isoflavones in the serum are found
      largely in the form of glucuronide and sulfur conjugates following soy
      consumption, little is known regarding the relative contributions of
      sulfotransferases in the liver and small intestine to isoflavone sulfation. Since
      the sulfates may be deconjugated in target tissues, circulating isoflavone
      sulfates may act as a source of tissue aglycones. In the current study genistein
      and daidzein sulfotransferase activities were measured in cytosol from human and
      rat liver and gastrointestinal tract. Isoflavone sulfation in the human
      gastrointestinal (GI) tract was correlated with activities towards substrates for
      previously characterized human sulfotransferases. Western blots of human cytosols
      were also conducted using antisera towards human sulfotransferases SULT1E1 and
      SULT2A1. Whereas rat liver was almost fourfold more active than small intestine
      in sulfation of genistein, in the human, activities in the two tissues were
      comparable. In contrast, intestinal sulfation of daidzein was comparable to
      hepatic sulfation in the rat and significantly greater in the human. Genistein
      and daidzein sulfation occurred throughout the human GI tract, but with a
      different distribution and different interindividual variability. Whereas
      genistein sulfation in the human GI tract correlated significantly with sulfation
      of the prototypical human phenolic sulfotransferase SULT1A family substrate 2
      naphthol (r2 = 0.71), daidzein sulfotransferase activity did not correlate with
      activities towards any prototypical sulfotransferase substrate or with genistein
      sulfation. Our results suggest that metabolism in the human GI tract has an
      important role in the generation of potentially bioactive isoflavone sulfates and
      a major role for the human phenolic sulfotransferase SULT1A family in metabolism
      of genistein in the gut. However, human intestinal daidzein sulfation appears to
      be catalyzed by a separate enzyme.

PMID- 17004898
TI  - Effect of traditional Greek Mediterranean meals on platelet aggregation in normal
      subjects and in patients with type 2 diabetes mellitus.
AB  - Patients with type 2 diabetes mellitus have increased risk of cardiovascular
      disease. Epidemiological studies have shown a correlation between diet and
      incidence of coronary heart disease. The aim of the study is to determine the
      effect of a traditional Greek Mediterranean diet on platelet aggregation induced
      by ADP, arachidonic acid (AA), and especially platelet-activating factor (PAF) on
      patients with type 2 diabetes mellitus as well as on healthy volunteers. The
      patients were randomized into two subgroups, A and B. The lipid extracts from
      traditional Greek Mediterranean-type meals were tested in in vivo for their
      ability to reduce PAF- or thrombin-induced platelet aggregation. The meals with
      the most potent anti-aggregating activity were chosen for the diet of both
      subgroup A and healthy subjects and consumed for a period of 28 days, whereas
      subgroup B kept to their regular diet that was followed before entering the
      study. Platelet-rich plasma was isolated before and after the diet, and the
      ability of platelets to aggregate under the aggregating factors was tested. One
      month consumption of diet resulted in a significant reduction in PAF- and ADP
      induced aggregation of platelets in both groups of healthy volunteers (PAF and
      ADP, P < .05) and subgroup A (PAF, P < .001; ADP, P < .05), whereas the AA
      induced aggregation was not affected. No effect was observed in subgroup B, which
      followed the standard diet. Thus the consumption of a traditional Greek
      Mediterranean diet even for a short period can reduce platelet activity in
      patients suffering from type 2 diabetes mellitus and in healthy subjects.

PMID- 17004899
TI  - Antioxidant properties of enzymatic hydrolysates from royal jelly.
AB  - Enzymatic hydrolysates were prepared from royal jelly using three enzymes
      (pepsin, trypsin, and papain), and their antioxidative properties were evaluated.
      The yield of these hydrolysates was very high, about 20-26% on a raw weight
      basis. In comparison with the antioxidative activities of water extract and
      alkaline extract of royal jelly, the antioxidative activities and scavenging
      activities against active oxygen species such as superoxide anion radical and
      hydroxyl radical of each hydrolysate were high in the sample with a low protein
      concentration. These results suggest that once royal jelly is hydrolyzed using
      enzyme, the hydrolysate possesses much higher antioxidative activity and
      scavenging activity against active oxygen species. Royal jelly will act as a
      medicinal food in the human body.

PMID- 17004900
TI  - Safety and antioxidant effects of a modest soy protein intervention in
      hemodialysis patients.
AB  - Antioxidant/anti-inflammatory effects of isoflavone-containing soy protein could
      partly explain why hemodialysis patients in Japan tend to outlive U.S.
      hemodialysis patients. However, a safety concern is that dialysis patients do not
      clear isoflavones well. A low-dose intervention with high isoflavone soy protein
      (25 g protein, four times a week for 4 weeks) was tested in 17 U.S. hemodialysis
      patients (eight given soy protein, nine given whey protein as a control). Soy
      protein intake produced no harmful effects based on a typical battery of blood
      safety tests. Post-treatment isoflavone levels, though high, were similar to
      those reported after a single 20-g soy protein intake by dialysis patients. In
      addition, intake of soy, but not whey, reduced plasma values for oxidized low
      density lipoprotein, a risk factor for cardiovascular disease, which is a common
      mortality cause in hemodialysis patients. Three other measures of oxidant stress
      and/or inflammation were unchanged by the modest high isoflavone soy protein
      intervention. In conclusion, in hemodialysis patients, a fairly short, low intake
      level intervention with high isoflavone soy protein produced no obvious harm, and
      produced one potentially beneficial effect. This justifies tests of higher-dose,
      longer interventions with soy protein in hemodialysis patients.

PMID- 17004901
TI  - Enhancement of erythrocyte antioxidants by green and black tea polyphenols during
      7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.
AB  - We evaluated the comparative chemopreventive efficacy of green tea polyphenols
      (polyphenon-E) and black tea polyphenols (polyphenon-B) on 7,12
      dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP)
      carcinogenesis. Lipid peroxidation, reduced and oxidized glutathione (GSH and
      GSSG, respectively), and the GSH-dependent enzymes glutathione peroxidase and
      glutathione S-transferase in the erythrocytes were used as biomarkers of
      chemoprevention. Enhanced lipid peroxidation in erythrocytes of DMBA-treated
      animals was accompanied by a significant decrease in the antioxidant status.
      Dietary administration of polyphenon-E and -B to DMBA-treated animals
      significantly decreased the extent of lipid peroxidation and enhanced the levels
      of GSH, GSH/GSSG ratio, and activities of GSH-dependent enzymes. Our study
      provides evidence that polyphenon-B is more effective in inhibiting HBP
      carcinogenesis than polyphenon-E by enhancing the antioxidant status, suggesting
      that polyphenon-B may have a major impact in the chemoprevention of oral cancer.

PMID- 17004902
TI  - Effects of policosanol on patients with ischemic stroke: a pilot open study.
AB  - Stroke is a major health problem worldwide. Its pharmacological management
      includes thrombolytic therapy for the acute phase and antiplatelet drugs for
      stroke recovery and prevention. Statins can help in the acute phase and in
      preventing stroke in secondary prevention patients. Policosanol is a cholesterol
      lowering drug with concomitant antiplatelet effects, with protective effects in
      stroke models. This observational study investigated the effects of policosanol
      (20 mg/day) administered during the acute phase and for 5 years later on the
      neurological recovery of patients with ischemic stroke treated with antiplatelets
      and vitamins. After hospital discharge, patients were followed up every 3 (first
      year) and 6 (thereafter) months. Neurological improvement was assessed with the
      modified Canadian Neurological Scale. Adverse events were recorded. Fifty
      patients were included; all completed the study. Neurological score improved
      throughout the study. No patient died, and most [40 (80.0%)] did not experience
      new vascular events; only one (2.0%) suffered a new stroke, and two (4.0%)
      suffered more than one transient ischemic attack. The time to the first recurrent
      event was 46.2 months. Policosanol persistently lowered serum total cholesterol,
      with such reduction correlating with the neurological improvement (R =
      0.995253301). Triglycerides were unchanged. Treatment was well tolerated.
      Policosanol administered to patients suffering ischemic stroke treated with
      aspirin and vitamins showed good results on neurological outcomes and recurrent
      events. This study, however, has limitations, since it was open and uncontrolled,
      and patients also consumed aspirin and vitamins. New randomized, controlled
      studies are needed to assess the usefulness of policosanol in stroke management.

PMID- 17004903
TI  - Anti-inflammatory and analgesic effects of Spartium junceum L. flower extracts: a
      preliminary study.
AB  - Our objective was to study the anti-inflammatory and analgesic activity of
      extract of Spartium junceum L. flowers. Samples of flowers were collected from
      wild plants, dried, powdered, and extracted with hexane and methanol. The
      extracts were evaporated to dryness and then suspended in suitable solvent. They
      were then tested for anti-inflammatory activity in the carrageenin rat paw edema
      test and for analgesic activity in the Randall and Selitto mechanical pressure
      test and in the tail-flick test. Twenty-four hours after treatment, the gastric
      mucosa of each rat was observed macroscopically. Based on these results the
      hexane extract was fractioned by column chromatography, and the fractions
      obtained were tested in the same way. The results showed good anti-inflammatory
      activity only for a single fraction of the hexane extract, while all the extracts
      and all the other hexane fractions showed both peripheral and central analgesic
      activity. In rats treated with the tested compounds hyperemia and ulcers were
      absent. The data from this preliminary study reveal interesting pharmacological
      properties of S. junceum L. flowers extract related to the marked analgesic
      activity and the absence of gastric ulcerogenic activity.

PMID- 17004904
TI  - Phytochemical and antimicrobial study of an antidiabetic plant: Scoparia dulcis
      L.
AB  - The antimicrobial and antifungal effects of different concentrations of
      chloroform/methanol fractions of Scoparia dulcis were investigated. The isolated
      fractions were tested against different bacteria like Salmonella typhii,
      Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas
      aeruginosa, and Proteus vulgaris and fungal strains such as Alternaria
      macrospora, Candida albicans, Aspergillus niger, and Fusarium oxysporum. The
      isolated fractions exhibited significant antimicrobial and antifungal activity
      against all the tested organisms compared with respective reference drugs. The
      isolated fractions of S. dulcis showed properties like antimicrobial and
      antifungal activities that will enable researchers in turn to look for
      application-oriented principles.

PMID- 17004905
TI  - Antibacterial principles from Myristica fragrans seeds.
AB  - Nutmeg (Myristica fragrans) is used in food preparations for its aromatic flavor.
      The present investigation was undertaken to evaluate the antibacterial activity
      of constituents of M. fragrans seeds. Seeds of M. fragrans were powdered and
      extracted with chloroform to obtain trimyristin, which on saponification yielded
      myristic acid. The mother liquor remaining after separation of trimyristin was
      concentrated and column-chromatographed with petroleum ether to separate
      myristicin. Antibacterial activity of these isolated constituents was evaluated
      by determination of minimum inhibitory concentration against selected Gram
      positive and Gram-negative organisms. All the constituents isolated from nutmeg
      exhibited good antibacterial activity. This study shows the potential of natural
      compounds in replacement of synthetic preservatives.

PMID- 17004906
TI  - Beneficial effects of coconut water feeding on lipid metabolism in cholesterol
      fed rats.
AB  - The purpose of this study was to determine the effect of coconut water feeding in
      cholesterol-fed rats. Male albino rats were fed tender coconut water and mature
      coconut water at a dose level of 4 mL/100 g of body weight. Cholesterol feeding
      caused a marked increase in total cholesterol, very low-density lipoprotein
      (VLDL) + low-density lipoprotein (LDL) cholesterol, and triglycerides in serum.
      Administration of coconut water counteracts the increase in total cholesterol,
      VLDL + LDL cholesterol, and triglycerides, while high-density lipoprotein
      cholesterol was higher. Lipid levels in the tissues viz. liver, heart, kidney,
      and aorta were markedly decreased in cholesterol-fed rats supplemented with
      coconut water. Feeding coconut water resulted in increased activities of 3
      hydroxy-3-methylglutaryl-CoA reductase in liver, lipoprotein lipase in heart and
      adipose tissue, and plasma lecithin:cholesterol acyl transferase, while lipogenic
      enzymes showed decreased activities. An increased rate of cholesterol conversion
      to bile acid and an increased excretion of bile acids and neutral sterols were
      observed in rats fed coconut water. Histopathological studies of liver and aorta
      revealed much less fatty accumulation in these tissues in cholesterol-fed rats
      supplemented with coconut water. Feeding coconut water resulted in increased
      plasma L-arginine content, urinary nitrite level, and nitric oxide synthase
      activity. These results indicate that both tender and mature coconut water has
      beneficial effects on serum and tissue lipid parameters in rats fed cholesterol
      containing diet.

PMID- 17004907
TI  - A pilot study of open label sesame oil in hypertensive diabetics.
AB  - The objective of this study was to investigate the effect of sesame oil in
      hypertensive diabetics medicated with atenolol (beta-blocker) and glibenclamide
      (sulfonylurea). This open label trial with two intervention periods comprised 22
      male and 18 female patients, 45-65 years old, with mild to moderate hypertension
      and diabetes. Sesame oil (Idhayam Gingelly oil, V.V.V. & Sons, Virudhunagar,
      Tamilnadu, India) was supplied to the patients, who were instructed to use it in
      place of other cooking oils for 45 days. Blood pressure (BP), anthropometric
      measurements, plasma glucose, glycated hemoglobin (HbA1c), lipid profiles [total
      cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density
      lipoprotein cholesterol, and triglycerides (TG)], lipid peroxidation
      [thiobarbituric acid-reactive substances (TBARS)], electrolytes (sodium,
      potassium, and chloride), and enzymic (superoxide dismutase, glutathione
      peroxidase, and catalase) and nonenzymic (vitamin C, vitamin E, beta-carotene,
      and reduced glutathione) antioxidants were measured at baseline and after 45 days
      of sesame oil substitution. The same patients were then switched over to other
      oils like palm or groundnut oils as their regular oils at random for another 45
      days, and the investigations were carried out again at the end. Systolic and
      diastolic BP decreased remarkably. When oil substitution was withdrawn, BP values
      rose again. Body weight, body mass index, girth of waist, girth of hip, and
      waist:hip ratio were reduced upon substitution of sesame oil. Plasma glucose,
      HbA1c, TC, LDL-C, and TG were decreased. TBARS level was reduced, while the
      activities of enzymic and the levels of nonenzymic antioxidants were increased.
      Plasma sodium levels were reduced, while potassium levels were elevated. These
      results indicate that substitution of sesame oil as the sole edible oil has an
      additive effect in further lowering BP and plasma glucose in hypertensive
      diabetics.

PMID- 17004908
TI  - Cholinergic basis of memory-strengthening effect of Foeniculum vulgare Linn.
AB  - Alzheimer's disease is a neurodegenerative disorder associated with a decline in
      cognitive abilities. Dementia is one of the age-related mental problems and a
      characteristic symptom of Alzheimer's disease. Nootropic agents are used in
      situations where there is organic disorder in learning abilities. The present
      work was undertaken to assess the potential of Foeniculum vulgare Linn. extract
      as a nootropic and anticholinesterase agent in mice. Methanolic extract of the
      whole plant of F. vulgare Linn. administered for eight successive days
      ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging- induced
      memory deficits in mice. The passive avoidance paradigm served as the
      exteroceptive behavioral model for assessing memory. F. vulgare extract increased
      step-down latency and acetylcholinesterase inhibition in mice significantly.
      Hence, F. vulgare can be employed in treatment of cognitive disorders such as
      dementia and Alzheimer's disease.

PMID- 17004909
TI  - Inhibitory effects of spice essential oils on the growth of Bacillus species.
AB  - A series of essential oils of 11 Turkish plant spices [black thyme, cumin, fennel
      (sweet), laurel, marjoram, mint, oregano, pickling herb, sage, savory, and
      thyme], used in foods mainly for their flavor, aromas, and preservation, in
      herbal tea, in alternative medicines, and in natural therapies, were screened for
      antibacterial effects at 1:50, 1:100, 1:250, and 1:500 dilutions by the paper
      disc diffusion method against six Bacillus species (Bacillus amyloliquefaciens
      ATCC 3842, Bacillus brevis FMC 3, Bacillus cereus FMC 19, Bacillus megaterium DSM
      32, Bacillus subtilis IMG 22, and B. subtilis var. niger ATCC 10). All of the
      tested essential oils (except for cumin) showed antibacterial activity against
      one or more of the Bacillus species used in this study. Generally, the essential
      oils at 1:50 and 1:100 levels were more effective. Only one essential oil
      (laurel) was not found effective against the tested bacteria. The bacterium most
      sensitive to all of the spice essential oils was B. amyloliquefaciens ATCC 3842.
      Based on the results of this study, it is likely that essential oils of some
      spices may be used as antimicrobial agents to prevent the spoilage of food
      products.

PMID- 17004910
TI  - Citrus juice modulates antioxidant enzymes and lipid profiles in orchidectomized
      rats.
AB  - Oxidative stress and hypogonadism are two factors linked to the increased
      incidence of cardiovascular disease in males. Eating fruits and vegetables is
      known to reduce the incidences of oxidative stress. The objective of this
      research was to delineate whether drinking daily squeezed orange juice (OJ) or
      grapefruit juice (GJ) modulates oxidative stress and antioxidant enzymes while
      impacting cardiovascular risk factors in hypogonad male rats. In the present
      study, 36 1-year-old male rats were equally divided among the following four
      treatments: sham (control), orchidectomized (ORX), ORX + OJ, and ORX + GJ. After
      60 days of drinking OJ or GJ, antioxidant capacity, cholesterol, and
      triglycerides in serum and superoxide dismutase (SOD), catalase (CAT),
      cholesterol, and triglycerides in liver were evaluated. Serum antioxidant
      capacity and SOD and CAT activities decreased (P < .05), while serum cholesterol
      and liver triglycerides increased (P < .05) in the ORX group compared with the
      sham group. In contrast to the ORX group, drinking OJ was ineffective while
      drinking GJ decreased (P < .05) cholesterol concentration in liver and in serum.
      Nevertheless, OJ and GJ decreased (P < .05) triglyceride concentration in liver
      and increased (P < .05) serum antioxidant capacity and SOD and CAT activities
      compared with the ORX group. In conclusion, drinking OJ or GJ prevented oxidative
      stress by enhancing total antioxidant capacity and elevating liver antioxidant
      enzymes while modulating cardiovascular risk factors.

PMID- 17004911
TI  - Differential effects of chitooligosaccharides on serum cytokine levels in aged
      subjects.
AB  - Free amine chitooligosaccharides (FACOS, Kitto Life, Seoul, Republic of Korea)
      with an average molecular mass of 3.5 kDa were efficiently produced using an
      ultrafiltration membrane reactor system. To evaluate the effect of
      chitooligosaccharides on serum cytokine levels in elderly adults after oral
      intake, 5.1 g/day of FACOS was given to elderly (age range, 74-86 years; mean, 80
      +/- 3 years) volunteers during an 8-week experimental period. Interleukin (IL)-12
      and interferona levels were significantly higher in the FACOS group than in the
      control group (P < .05). However, levels of the inflammatory cytokines IL-1beta
      and tumor necrosis factor-alpha decreased after FACOS intake during the
      experimental period. The results of this study suggest that the oral intake of
      chitooligosaccharides may have beneficial effects on specific cell-mediated
      immunity while also acting as an anti-inflammatory agent in aged subjects.

PMID- 17004912
TI  - Mulberry extract supplements ameliorate the inflammation-related hematological
      parameters in carrageenan-induced arthritic rats.
AB  - Mulberry fruit (Morus Lhou Koidz.), a rich source of the major anthocyanin,
      cyanidin 3-glucoside (C3G), has traditionally been used for the treatment of
      inflammatory conditions including rheumatic arthritis. In this study, we
      evaluated the efficacy of orally administrated methanolic mulberry fruit extract
      (ME) in carrageenan-induced arthritic rats, based on previously observed in vitro
      antioxidant and anti-inflammatory activities. A significant attenuation of hind
      paw inflammation characterized by fluid accumulation, uric acid production, and
      rheumatoid factors induced by carrageenan was observed following the intake of
      both ME (50 mg/kg of body weight) and C3G (10 mg/kg of body weight). Moreover,
      alterations in hematological parameters such as serum triglyceride, high-density
      lipoprotein-cholesterol, and atherogenic index following carrageenan
      administration were partially reversed by the administration of ME. It is
      concluded that dietary mulberry fruit extracts elicited protection against
      carrageenan-induced inflammation.

PMID- 17004913
TI  - Detection of isoflavones in mouse tibia after feeding daidzein.
AB  - Many studies suggest that diets rich in isoflavones protect against bone loss or
      slow the loss of bone mass that occurs because of estrogen withdrawal. Although
      in vitro studies have reported effects of isoflavones on bone cells, the presence
      of daidzein and/or equol in bone tissue in vivo has not been reported. The
      objective of this study was to determine if daidzein and equol were present in
      bone tissue (tibias) after feeding mice a diet containing purified daidzein. Sham
      mice (n = 9) received control diet, and ovariectomized mice were randomized to
      control diet (Ovx) (n = 9) or control diet containing 200 mg of daidzein/kg of
      diet (n = 8) for 12 weeks. At necropsy, tibias and serum were collected. Mice in
      the Daidzein group had significantly higher (P < .05) levels of both daidzein and
      equol in tibias than Sham and Ovx mice. Tibia levels of daidzein and equol were
      approximately five and four times higher, respectively, than the Sham and Ovx
      groups. Similarly, mice fed daidzein also had significantly higher (P < .05)
      serum daidzein and equol than the Sham and Ovx mice. In conclusion, feeding a
      level of daidzein that is attainable by dietary intervention alone results in a
      high level of both daidzein and equol in tibias. These findings suggest that
      daidzein and its metabolite, equol, have the potential to act directly on bone
      cells in vivo.

PMID- 17004914
TI  - Improvement in human semen quality after oral supplementation of vitamin C.
AB  - This study was carried out to monitor the effect of oral supplementation of
      vitamin C on various semen parameters in oligospermic, infertile, otherwise
      healthy individuals. Various semen parameters, including sperm motility, sperm
      count, and sperm morphology, were studied before and after the vitamin C
      treatment. A total of 13 infertile patients were included. Their ages ranged
      between 25 and 35 years. They had no genital infection or varicocele. Physical
      examination and other routine laboratory investigations were normal. General
      semen analysis revealed oligozoospermia (mean sperm count was 14.3 +/- 7.38 x
      10(6) sperms/mL, mean sperm with normal morphology was 43 +/- 7.87%, and mean
      sperm motility was 31.2 +/- 9.61%). Testicular biopsy was not done. These
      patients received in an open trial of 1,000 mg of vitamin C twice daily for a
      maximum of 2 months. Results showed that the mean sperm count was increased to
      32.8 +/- 10.3 x 10(6) sperms/mL (P < .001) after 2 months of vitamin C intake.
      The mean sperm motility was increased significantly to 60.1 +/- 8.47% (P < .001),
      and mean sperms with normal morphology increased significantly to 66.7 +/- 4.77%
      (P < .001). This study showed that vitamin C supplementation in infertile men
      might improve sperm count, sperm motility, and sperm morphology and might have a
      place as an additional supplement to improve the semen quality towards
      conception.

PMID- 17004915
TI  - Evolutionarily-conserved role of the NF-kappaB transcription factor in neural
      plasticity and memory.
AB  - NF-kappaB is an evolutionarily conserved family of transcription factors (TFs)
      critically involved in basic cellular mechanisms of the immune response,
      inflammation, development and apoptosis. In spite of the fact that it is
      expressed in the central nervous system, particularly in areas involved in memory
      processing, and is activated by signals such as glutamate and Ca2+, its role in
      neural plasticity and memory has only recently become apparent. A surprising
      feature of this molecule is its presence within the synapse. An increasing number
      of reports have called attention to the role of this TF in processes that require
      long-term regulation of the synaptic function underlying memory and neural
      plasticity. Here we review the evidence regarding a dual role for NF-kappaB, as
      both a signalling molecule after its activation at the synapse and a
      transcriptional regulator upon reaching the nucleus. The specific role of this
      signal, as well as the general transcriptional mechanism, in the process of
      memory formation is discussed. Converging lines of evidence summarized here point
      to a pivotal role for the NF-kappaB transcription factor as a direct signalling
      mechanism in the regulation of gene expression involved in long-term memory.

PMID- 17004916
TI  - Animal models of migraine: looking at the component parts of a complex disorder.
AB  - Animal models of human disease have been extremely helpful both in advancing the
      understanding of brain disorders and in developing new therapeutic approaches.
      Models for studying headache mechanisms, particularly those directed at migraine,
      have been developed and exploited efficiently in the last decade, leading to
      better understanding of the potential mechanisms of the disorder and of the
      action for antimigraine treatments. Model systems employed have focused on the
      pain-producing cranial structures, the large vessels and dura mater, in order to
      provide reproducible physiological measures that could be subject to
      pharmacological exploration. A wide range of methods using both in vivo and in
      vitro approaches are now employed; these range from manipulation of the mouse
      genome in order to produce animals with human disease-producing mutations,
      through sensitive immunohistochemical methods to vascular, neurovascular and
      electrophysiological studies. No one model system in experimental animals can
      explain all the features of migraine; however, the systems available have begun
      to offer ways to dissect migraine's component parts to allow a better
      understanding of the problem and the development of new treatment strategies.

PMID- 17004918
TI  - Brain-derived neurotrophic factor facilitates in vivo internalization of tetanus
      neurotoxin C-terminal fragment fusion proteins in mature mouse motor nerve
      terminals.
AB  - In a previous study it was reported that fusion proteins composed of the atoxic C
      terminal fragment of tetanus toxin (TTC) and green fluorescent protein or beta
      galactosidase (GFP-TTC and beta-gal-TTC, respectively) rapidly cluster at motor
      nerve terminals of the mouse neuromuscular junction (NMJ). Because this traffic
      involves presynaptic activity, probably via the secretion of active molecules, we
      examined whether it is affected by brain-derived neurotrophic factor (BDNF).
      Quantitative confocal microscopy and a fluorimetric assay for beta-gal activity
      revealed that co-injecting BDNF and the fusion proteins significantly increased
      the kinetics and amount of the proteins' localization at the NMJ and their
      internalization by motor nerve terminals. The observed increases were independent
      of synaptic vesicle recycling because BDNF did not affect spontaneous quantal
      acetylcholine release. In addition, injecting anti-BDNF antibody shortly before
      injecting GFP-TTC, and before co-injecting GFP-TTC and BDNF, significantly
      reduced the fusion protein's localization at the NMJ. Co-injecting GFP-TTC with
      neurotrophin-4 (NT-4) or glial-derived neurotrophic factor (GDNF), but not with
      nerve growth factor, neurotrophin-3 or ciliary neurotrophic factor, also
      significantly increased the fusion protein's localization at the NMJ. Thus, TTC
      probes may use for their neuronal internalization endocytic pathways normally
      stimulated by BDNF, NT-4 and GDNF binding. Different tyrosine kinase receptors
      with similar signalling pathways are activated by BDNF/NT-4 and GDNF binding.
      Thus, activated components of these signalling pathways may be involved in the
      TTC probes' internalization, perhaps by facilitating localization of receptors of
      TTC in specific membrane microdomains or by recruiting various factors needed for
      internalization of TTC.

PMID- 17004917
TI  - Targeted transgene expression in neuronal precursors: watching young neurons in
      the old brain.
AB  - Progress in the field of neurogenesis is limited by the lack of animal models
      allowing direct detection and analysis of living cells participating in
      neurogenesis. We engineered a transgenic mouse model that expresses the
      fluorescent reporter proteins enhanced green fluorescent protein or Discoma sp.
      reef coral red fluorescent protein under the control of the doublecortin (DCX)
      promoter, a gene specifically and transiently active in neuronal precursors and
      young neurons. The expression of the reporter proteins correlated with expression
      of the endogenous DCX protein, and with developmental and adult neurogenesis.
      Neurogenesis was unaffected by the presence of the fluorescent proteins. The
      transgenic mice allowed direct identification of the very few newly generated
      neurons present in the aged brain. We performed electrophysiological analysis and
      established that newly generated hippocampal granule cells in aged and young mice
      shared identical physiological properties. Hence, although the rate of
      neurogenesis tapers with ageing, a population of highly excitable young neurons
      indistinguishable to those found in younger animals is continuously generated.
      Therefore, maintenance of the fundamental properties of neuronal precursors even
      at advanced age suggests that stimulation of neurogenesis may constitute a valid
      strategy to counteract age-related neuronal loss and cognitive declines.

PMID- 17004919
TI  - The axotomy-induced neuropeptides galanin and pituitary adenylate cyclase
      activating peptide promote axonal sprouting of primary afferent and cranial motor
      neurones.
AB  - The neuropeptides galanin and pituitary adenylate cyclase-activating peptide
      (PACAP) are markedly up-regulated in response to peripheral nerve lesion. Both
      peptides are involved in neuronal differentiation and neurite outgrowth during
      development. In this study, we investigated the effects of galanin and PACAP on
      axonal elongation and sprouting by adult rat sensory neurones in vitro and facial
      motor neurones in vivo. Dissociated rat dorsal root ganglion neurones were plated
      on laminin substrate and analysed morphometrically. Both the mean axonal length
      and the number of branch points significantly increased in the presence of
      galanin or PACAP (2-5 microm). Effects on axonal collateralization were
      investigated in the rat facial nerve lesion model by direct application of the
      peptides to collagen-filled conduits entubulating the transected facial nerve
      stumps. Triple retrograde labelling of brainstem neurones confirmed that the
      peptides potently induce axonal sprouting of cranial motor neurones. The number
      of neurones regenerating into identified rami of the facial nerve increased up to
      fivefold. Biometrical analysis of whisking behaviour revealed that galanin and
      PACAP impaired the functional outcome when compared with vehicle-treated animals
      8 weeks after surgery. In conclusion, although galanin and PACAP have been
      established as neurotrophic molecules with respect to axonal development and
      regeneration, their potential as treatments for peripheral nerve lesions appears
      limited because of the extensive stimulation of collateral axon branching. These
      branches are misrouted towards incorrect muscles and cause impairment in their
      coordinated activity.

PMID- 17004920
TI  - The vasopressin-induced excitation of hypoglossal and facial motoneurons in young
      rats is mediated by V1a but not V1b receptors, and is independent of
      intracellular calcium signalling.
AB  - As a hormone, vasopressin binds to three distinct receptors: V1a and V1b
      receptors, which induce phospholipase-Cbeta (PLCbeta) activation and Ca2+
      mobilization; and V2 receptors, which are coupled to adenylyl cyclase. V1a and
      V1b receptors are also present in neurons. In particular, hypoglossal (XII) and
      facial (VII) motoneurons are excited following vasopressin-V1a receptor binding.
      The aim of the present study was double: (i) to determine whether V1b receptors
      contribute to the excitatory effect of vasopressin in XII and VII motoneurons;
      and (ii) to establish whether the action of vasopressin on motoneurons is
      mediated by Ca2+ signalling. Patch-clamp recordings were performed in brainstem
      slices of young rats. Vasopressin depolarized the membrane or generated an inward
      current. By contrast, [1-deamino-4-cyclohexylalanine] arginine vasopressin
      (d[Cha4]AVP), a V1b agonist, had no effect. The action of vasopressin was
      suppressed by Phaa-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2, a V1a antagonist, but
      not by SSR149415, a V1b antagonist. Thus, the vasopressin-induced excitation of
      brainstem motoneurons was exclusively mediated by V1a receptors. Light
      microscopic autoradiography failed to detect V1b binding sites in the facial
      nucleus. In motoneurons loaded with GTP-gamma-S, a non-hydrolysable analogue of
      GTP, the effect of vasopressin was suppressed, indicating that neuronal V1a
      receptors are G-protein-coupled. Intracellular Ca2+ chelation suppressed a Ca2+
      activated potassium current, but did not affect the vasopressin-evoked current.
      H7 and GF109203, inhibitors of protein kinase C, were without effect on the
      vasopressin-induced excitation. U73122 and D609, PLCbeta inhibitors, were also
      without effect. Thus, excitation of brainstem motoneurons by V1a receptor
      activation is probably mediated by a second messenger distinct from that
      associated with peripheral V1a receptors.

PMID- 17004921
TI  - Modulation of p75-dependent motor neuron death by a small non-peptidyl mimetic of
      the neurotrophin loop 1 domain.
AB  - The p75 neurotrophin receptor (p75NTR) is expressed by degenerating spinal motor
      neurons in amyotrophic lateral sclerosis (ALS). The mature and pro-form of nerve
      growth factor (NGF) activate p75NTR to trigger motor neuron apoptosis. However,
      attempts to modulate p75NTR-mediated neuronal death in ALS models by
      downregulating or antagonizing p75NTR with synthetic peptides have led to only
      modest results. Recently, a novel ligand of p75NTR, compound LM11A-24, has been
      identified. It is a non-peptidyl mimetic of the neurotrophin loop 1 domain that
      promotes hippocampal neuron survival through p75NTR and exerts protection against
      p75NTR-mediated apoptosis of oligodendrocytes induced by proNGF. Thus, LM11A-24
      appears to activate p75NTR-linked survival but not death mechanisms, and may
      interfere with the ability of neurotrophins to induce apoptosis. Given these
      findings, we hypothesized that LM11A-24 might be a particularly potent inhibitor
      of motor neuron degeneration. We examined the effects of LM11A-24 on apoptosis of
      cultured rat embryonic motor neurons. Interestingly, in contrast to the effects
      observed in hippocampal cultures, LM11A-24 was unable to prevent motor neuron
      apoptosis induced by trophic factor deprivation. However, picomolar
      concentrations of LM11A-24 prevented p75NTR-dependent motor neuron death induced
      by either exogenous addition of NGF or spinal cord extracts from symptomatic
      superoxide dismutase-1G93A mice, in the presence of low steady-state
      concentrations of nitric oxide. LM11A-24 also inhibited motor neuron death
      induced by NGF-producing reactive astrocytes in co-culture conditions. These
      studies suggest that modulation of p75NTR by small molecule ligands targeting
      this receptor might constitute a novel strategy for preventing motor neuron
      degeneration.

PMID- 17004922
TI  - Functional redundancy of NSCL-1 and NeuroD during development of the petrosal and
      vestibulocochlear ganglia.
AB  - To study the role of different members of the bHLH gene family for sensory organ
      development we have generated NSCL-1 and NeuroD compound-mutant mice. Double
      homozygous animals were characterized by a more severe reduction of the petrosal
      and vestibulocochlear ganglia than NeuroD-knockout mice. The more severe
      reduction of the petrosal and vestibulocochlear ganglia in double-knockout mice
      indicates overlapping functions of the two genes during neuronal development.
      Interestingly, we also found that the two genes are jointly regulated by thyroid
      hormone during sensory hair cell development. We further present a detailed
      expression analysis of NSCL-1 and NSCL-2 during sensory neuron development. NSCL
      1 expression was detected in all developing cranial ganglia including the
      petrosal and vestibulocochlear ganglion, in inner and outer hair cells of the
      organ of Corti and in hair cells of the vestibular system. Expression domains in
      other sensory structures include the retina, Merkel cells of the developing skin
      and sensory cells of the tongue. The expression of NSCL-2 was restricted to
      developing cranial ganglia, the retina and the vestibular nerve. Both NSCL-1 and
      NSCL-2 genes are active only in postmitotic neurons, indicating a role for
      neuronal cell migration and/or differentiation within the sensory system.

PMID- 17004923
TI  - Ryanodine receptor-transmitter release site coupling increases quantal size in a
      synapse-specific manner.
AB  - The mechanisms by which presynaptic neurones differentially regulate synaptic
      transmission with multiple postsynaptic targets in the brain are not fully
      understood. Using intracellular sharp electrode and whole-cell voltage-clamp
      recordings of soma-soma synapses between identified Lymnaea neurones, we provide
      direct evidence that quantal size is regulated presynaptically through the
      coupling of multiple release sites. This coupling effectively multiplies quantal
      size, thereby providing significant influence over parameters of synaptic
      transmission that are influenced by quantal size, such as the variance in
      transmitter release at stationary release probabilities. Variation in the degree
      of coupling is dependent on the identity of the postsynaptic cell, even though
      the variation in quantal size is of presynaptic origin. We have therefore
      demonstrated the presence of a novel mechanism by which presynaptic neurones may
      differentially regulate quantal size at select synaptic connections, in turn
      providing them with a means of regulating synaptic transmission with multiple
      postsynaptic cells.

PMID- 17004924
TI  - Long-lasting synaptic loss after repeated induction of LTD: independence to the
      means of LTD induction.
AB  - Short- and long-lasting synaptic plasticity is assumed to be the cellular basis
      of short- and long-lasting memory, respectively. However, the cellular
      consequences leading to the long-lasting synaptic plasticity, assumed to include
      the processes of synapse formation and elimination, remain unknown. Using
      hippocampal slices maintained stably in culture, we found previously that the
      repeated induction of long-term potentiation (LTP) triggered a slowly developing
      long-lasting enhancement in synaptic transmission strength accompanied by synapse
      formation, which was separate from LTP itself. We recently reported a phenomenon
      apparently of a mirror-image effect. The repeated activations of metabotropic
      glutamate receptor (mGluR), which induces long-term depression (LTD), triggered a
      long-lasting reduction in synaptic strength accompanied by synapse elimination.
      To clarify whether the reported long-lasting effect was specific to the drugs
      used previously and whether the effect was specific to mGluR-mediated LTD, we
      exposed the cultured slices repeatedly to another Group I metabotropic glutamate
      receptor (mGluR) agonist, an N-methyl-d-aspartate receptor agonist, and a Na+/K+
      pump inhibitor. All these treatments resulted in an equivalent long-lasting
      synaptic reduction/elimination when repeated three times, indicating that the
      repeated LTD induction leads to synapse elimination. The independence of synapse
      elimination to the means of LTD induction suggests that the signals leading to
      short-term plasticity and long-term plasticity are independent. Detailed
      inspections in the representative case of mGluR activation revealed that the
      reduction in synaptic strength developed with a approximately 1-week delay from
      the decrease in the number of synaptic structures. This synapse elimination
      should be unique as it is activity-dependent rather than inactivity-dependent.

PMID- 17004925
TI  - ERK1/2 but not p38 MAP kinase is essential for the long-term depression in mouse
      cerebellar slices.
AB  - Mitogen-activated protein kinase (MAPK) cascade is essential for synaptic
      plasticity and learning. In the hippocampus, three different MAPK subfamilies,
      extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK and c-Jun NH2
      terminal protein kinase (JNK), selectively regulate activity-dependent glutamate
      receptor trafficking during long-term potentiation (LTP), long-term depression
      (LTD), and depotentiation after LTP, respectively. Although LTP and LTD at
      cerebellar parallel fibre (PF)-Purkinje cell synapses are thought to be
      controlled by glutamate receptor trafficking, the involvement of MAPK subfamilies
      has not been systemically studied in cerebellar slice preparations. To clarify
      the role of the MAPK cascade in cerebellar LTD, we performed biochemical and
      electrophysiological analyses using ICR mouse cerebellar slices. Immunoblot
      analyses using phosphorylation-specific antibodies for MAPKs revealed that among
      the three MAPKs, ERK1/2 was specifically activated by phorbol ester, which could
      induce LTD in cerebellar slices. In addition, U0126, a specific inhibitor of the
      MAPK kinase-ERK1/2 pathway, abrogated the induction of LTD in cerebellar slices,
      whereas SB203580 and SP600125, specific inhibitors of p38 MAPK and JNK,
      respectively, had no effect. Although metabotropic glutamate receptor 1 (mGluR1)
      has been suggested as a possible downstream target of ERK1/2 in cell-culture
      preparations, mGluR1-activated slow excitatory postsynaptic currents (EPSCs) were
      not affected by U0126 treatment in slices. These findings indicate that unlike
      hippocampal LTD mediated by p38 MAPK, glutamate receptor trafficking during
      cerebellar LTD was regulated by a distinct mechanism involving ERK1/2 in slice
      preparations.

PMID- 17004926
TI  - Dendritic excitability and calcium signalling in the mitral cell distal
      glomerular tuft.
AB  - The processing of odour information starts at the level of the olfactory
      glomerulus, where the mitral cell distal dendritic tuft not only receives
      olfactory nerve sensory input but also generates dendrodendritic output to form
      complicated glomerular synaptic circuits. Analysing the membrane properties and
      calcium signalling mechanisms in these tiny dendritic branches is crucial for
      understanding how the glomerular tuft transmits and processes olfactory signals.
      With the use of two-photon Ca2+ imaging in rat olfactory bulb slices, we found
      that these distal dendritic branches displayed a significantly larger Ca2+ signal
      than the soma and primary dendrite trunk. A back-propagating action potential was
      able to trigger a Ca2+ increase throughout the entire glomerular tuft, indicative
      of the presence of voltage-gated Ca2+ conductances in all branches at different
      levels of ramification. In response to a train of action potentials evoked at 60
      Hz from the soma, the tuft Ca2+ signal increased linearly with the number of
      action potentials, suggesting that these glomerular branches were able to support
      repetitive penetration of Na+ action potentials. When a strong olfactory nerve
      excitatory input was paired with an inhibition from mitral cell basal dendrites,
      a small spike-like fast prepotential was revealed at both the soma and distal
      primary dendrite trunk. Corresponding to this fast prepotential was a Ca2+
      increase confined locally within the glomerular tuft. In summary, the mitral cell
      distal dendritic tuft possesses both Na+ and Ca2+ voltage-dependent conductances
      which can mediate glomerular Ca2+ responsiveness critical for dendrodendritic
      output and synaptic plasticity.

PMID- 17004927
TI  - Differential effect of cannabinoid agonists and endocannabinoids on histamine
      release from distinct regions of the rat brain.
AB  - Cannabinoids exert complex actions on neurotransmitter systems involved in
      cognition, locomotion, appetite, but no information was available so far on the
      interactions between the endocannabinoid system and histaminergic neurons that
      command several, similar behavioural states and memory. In this study, we
      investigated the effect of cannabimimetic compounds on histamine release using
      the microdialysis technique in the brain of freely moving rats. We found that
      systemic administration of the cannabinoid receptors 1 (CB1-r) agonist
      arachidonyl-2'chloroethylamide/N-(2chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide
      (ACEA; 3 mg/kg) increased histamine release from the posterior hypothalamus,
      where the histaminergic tuberomamillary nuclei (TMN) are located. Local infusions
      of ACEA (150 nm) or R(+)-methanandamide (mAEA; 1 microm), another CB1-r agonist,
      in the TMN augmented histamine release from the TMN, as well as from two
      histaminergic projection areas, the nucleus basalis magnocellularis and the
      dorsal striatum. When the endocannabinoid uptake inhibitor AM404 was infused into
      the TMN, however, increased histamine release was observed only in the TMN. The
      cannabinoid-induced effects on histamine release were blocked by co
      administrations with the CB1-r antagonist AM251. Using double-immunofluorescence
      labelling and confocal laser-scanning microscopy, CB1-r immunostaining was found
      in the hypothalamus, but was not localized onto histaminergic cells. The
      modulatory effect of cannabimimetic compounds on histamine release apparently did
      not involve inhibition of gamma-aminobutyric acid (GABA)ergic neurotransmission,
      which provides the main inhibitory input to the histaminergic neurons in the
      hypothalamus, as local infusions of ACEA did not modify GABA release from the
      TMN. These profound effects of cannabinoids on histaminergic neurotransmission
      may partially underlie some of the behavioural changes observed following
      exposure to cannabinoid-based drugs.

PMID- 17004928
TI  - Insulin-like growth factor binding proteins: regulation in chronic active plaques
      in multiple sclerosis and functional analysis of glial cells.
AB  - Studies in experimental allergic encephalomyelitis, an animal model of multiple
      sclerosis (MS), suggest that astrocyte-secreted insulin-like growth factor
      binding protein-2 (IGFBP-2) helps target IGF-1 to IGF-1 receptor-expressing
      oligodendrocytes and promote remyelination. We examined the presence of IGFBPs 1
      6 in astrocytes in normal post-mortem human brain tissue and lesions of MS by
      means of immunohistochemistry. Under normal conditions all six IGFBPs were
      detected. Compared to controls, hypertrophic astrocytes at the borders of chronic
      active MS lesions displayed increased immunoreactivity for IGFBP-2 and IGFBP-4.
      In vitro studies were performed to analyse the effects of IGFBPs on cellular
      proliferation of neonatal rat glial cells. Treatment of astrocytes with IGF-1 and
      -2 enhanced proliferation whereas IGFBP-2 and -4 inhibited cellular growth.
      Interestingly, combined treatment with IGFBP-2 and IGF-1 potentiated effects on
      cellular proliferation whereas combined treatment with IGFBP-2 and IGF-2
      inhibited growth. Unlike IGFBP-2, IGFBP-4 inhibited proliferation in combined
      treatment with IGF-1. In contrast, combined treatment with IGFBP-2 and IGF-1
      resulted in decreased cell survival of oligodendrocyte precursor cells. Our
      results suggest that the up-regulation of IGFBP-2 in reactive astrocytes in MS
      lesions may primarily serve to enhance the IGF-1-mediated mitogenic stimulus for
      astrocytes rather than supporting oligodendrocyte survival.

PMID- 17004929
TI  - Altered PPARgamma expression and activation after transient focal ischemia in
      rats.
AB  - Stroke is a devastating disease with limited treatment options. Recently, we
      found that the peroxisome proliferator-activated receptor-gamma (PPARgamma)
      agonists troglitazone and pioglitazone reduce injury and inflammation in a rat
      model of transient cerebral ischemia. The mechanism of this protection is
      unclear, as these agents can act through PPAR-gamma activation or through PPAR
      gamma-independent mechanisms. Therefore, we examined PPAR-gamma expression, DNA
      binding and transcriptional activity following stroke. In addition, we used a
      PPAR-gamma antagonist, T0070907, to determine the role of PPAR-gamma during
      ischemia. Using immunohistochemical techniques and real-time PCR, we found low
      levels of PPAR-gamma mRNA and PPAR-gamma immunoreactivity in nonischemic brain;
      however, PPAR-gamma expression dramatically increased in ischemic neurons,
      peaking 24 h following middle cerebral artery occlusion. Interestingly, we found
      that in both vehicle- and agonist-treated brains, DNA binding was reduced in the
      ischemic hemisphere relative to the contralateral hemisphere. Expression of a
      PPAR-gamma target gene, lipoprotein lipase, was also reduced in ischemic relative
      to nonischemic brain. Both DNA binding and lipoprotein lipase expression were
      increased by the addition of the PPAR-gamma agonist rosiglitazone. Finally, we
      found that rosiglitazone-mediated protection after stroke was reversed by the
      PPAR-gamma antagonist T0070907. Interestingly, infarction size was also increased
      by T0070907 in the absence of PPAR-gamma agonist, suggesting that endogenous PPAR
      gamma ligands may mitigate the effects of cerebral ischemia.

PMID- 17004930
TI  - Nyctalopin is essential for synaptic transmission in the cone dominated zebrafish
      retina.
AB  - The first synapse in the vertebrate visual system is the photoreceptor synapse
      between rod and cone photoreceptors and the second-order bipolar cells. Although
      mutations in the nyctalopin gene (NYX) in humans lead to congenital stationary
      night blindness (CSNB1), affecting synaptic transmission between both types of
      photoreceptors and ON-bipolar cells, the function of nyctalopin in cone-dominant
      animal models has not been studied. Because the larval zebrafish retina is cone
      dominant, we isolated the zebrafish nyx ortholog and raised a polyclonal antibody
      against the protein. Nyctalopin is expressed postsynaptically in both synaptic
      layers of the retina. Functional disruption via morpholino antisense injection
      leads to characteristic defects in the electroretinogram and defects in visual
      contrast sensitivity. We therefore demonstrated that nyctalopin plays a similar
      role in retinal synapse function in the cone pathway as in the rod pathway,
      thereby creating a genetic model for CSNB1 and its effects on cone vision.

PMID- 17004931
TI  - Localization of heterotypic gap junctions composed of connexin45 and connexin36
      in the rod pathway of the mouse retina.
AB  - The primary rod pathway in mammals contains gap junctions between AII amacrine
      cells and ON cone bipolar cells which relay the rod signal into the cone pathway
      under scotopic conditions. Two gap junctional proteins, connexin36 (Cx36) and
      connexin45 (Cx45), appear to play a pivotal role in this pathway because lack of
      either protein leads to an impairment of visual transmission under scotopic
      conditions. To investigate whether these connexins form heterotypic gap junctions
      between ON cone bipolar and AII amacrine cells, we used newly developed Cx45
      antibodies and studied the cellular and subcellular distribution of this protein
      in the mouse retina. Specificity of the Cx45 antibodies was determined, among
      others, by Western blot and immunostaining of mouse heart, where Cx45 is
      abundantly expressed. In mouse retina, Cx45 immunosignals were detected in both
      plexiform layers and the ganglion cell layer. Double staining for Cx45 and Cx36
      revealed a partial overlap in the punctate patterns in the ON sublamina of the
      inner plexiform layer of the retina. We quantified the distributions of these two
      connexins in the ON sublamina, and detected 30% of the Cx45 signals to be co
      localized with or in close apposition to Cx36 signals. Combining immunostaining
      and intracellular dye injection revealed an overlap or tight association of Cx36
      and Cx45 signals on the terminals of injected AII amacrine and two types of ON
      cone bipolar cells. Our results provide direct evidence for heterotypic gap
      junctions composed of Cx36 and Cx45 between AII amacrine and certain types of ON
      cone bipolar cells.

PMID- 17004932
TI  - Competition between glucose and lactate as oxidative energy substrates in both
      neurons and astrocytes: a comparative NMR study.
AB  - Competition between glucose and lactate as oxidative energy substrates was
      investigated in both primary cultures of astrocytes and neurons using
      physiological concentrations (1.1 mm for each). Glucose metabolism was
      distinguished from lactate metabolism by using alternatively labelled substrates
      in the medium ([1-13C]glucose + lactate or glucose + [3-13C]lactate). After 4 h
      of incubation, 1H and 13C-NMR spectra were realized on perchloric acid extracts
      of both cells and culture media. For astrocytic cultures, spectra showed that
      amino acids (glutamine and alanine) were more labelled in the glucose-labelled
      condition, indicating that glucose is a better substrate to support oxidative
      metabolism in these cells. The opposite was observed on spectra from neuronal
      cultures, glutamate being much more labelled in the lactate-labelled condition,
      confirming that neurons consume lactate preferentially as an oxidative energy
      substrate. Analysis of glutamine and glutamate peaks (singlets or multiplets)
      also suggests that astrocytes have a less active oxidative metabolism than
      neurons. In contrast, they exhibit a stronger glycolytic metabolism than neurons
      as indicated by their high lactate production yield. Using a mathematical model,
      we have estimated the relative contribution of exogenous glucose and lactate to
      neuronal oxidative metabolism. Under the aforementioned conditions, it represents
      25% for glucose and 75% for lactate. Altogether, these results obtained on
      separate astrocytic and neuronal cultures support the idea that lactate,
      predominantly produced by astrocytes, is used as a supplementary fuel by neurons
      in vivo already under resting physiological conditions.

PMID- 17004933
TI  - Changes in extracellular hypothalamic glucose in relation to feeding.
AB  - The aim of the present in vivo microdialysis study was to investigate the
      relation between feeding and changes in glucose concentrations in the rat
      ventromedial hypothalamus (VMH). Absolute ambient glucose concentrations in VMH
      were 1.43 mm in non-deprived rats as compared to 0.94 mm after 24-h food
      deprivation. To examine whether feeding influences hypothalamic glucose, changes
      of glucose concentration over time were determined relative to a baseline.
      Experiments were conducted in relation to both, nutritional state (food-deprived
      rats vs. non-deprived rats) and feeding conditions throughout the experiment
      (freely feeding rats vs. rats without access to food). The results of this
      microdialysis study show clearly that glucose concentration in the VMH of rats
      increases significantly in relation to food intake. The data demonstrate that a
      24-h food deprivation before the experiment further augments this increase (up to
      350% from baseline) as compared to non-deprived conditions (up to 60% from
      baseline). However, the magnitude of food related increase in VMH glucose does
      not correlate with the individual amount of food eaten. In conclusion, the
      present study shows for the first time that VMH glucose concentrations increase
      with food intake in the early dark phase, indicating that such changes do not
      only occur after pharmacological treatment, but also under physiological feeding
      conditions. The results further indicate that the feeding related increase in VMH
      glucose depends on the nutritional state of the organism.

PMID- 17004934
TI  - Distinct patterns of plasticity in prefrontal cortex neurons that encode slow and
      fast responses to stress.
AB  - The prefrontal cortex (PFC) has been implicated in cognitive and affective
      responses to acute and chronic stress; however, direct evidence for the
      reactivity or adaptability of PFC neurons to stress is lacking. We followed the
      unit activity of medial PFC (mPFC) neurons in awake rats during two consecutive
      exposures to restraint stress or to a non-aversive novel object. The majority
      (75%) of mPFC neurons had significant responses to the initial restraint that was
      differentiated into one of three temporal patterns: (i) phasic increase in firing
      rate during the restraint period, (ii) slow onset increase in firing rate that
      was sustained for > 2 h after restraint, and (iii) brief bi-phasic responses to
      initiation and termination of restraint. Exposure to a novel object elicited an
      exposure-locked phasic response in 40% of the neurons. None of the neurons
      displayed the sustained activation that was prominent after restraint. A second
      exposure to the object no longer elicited this phasic response while neurons in
      the three restraint-responsive groups modified their firing rate during the
      second restraint in a manner that was specific to their pattern of response to
      the first restraint. These findings demonstrate that whereas some mPFC neurons
      respond phasically to novel stimuli irrespective of their aversive nature, a
      separate population of PFC neurons responds to a stressful stimulus with a
      sustained increase in firing rate that persists in the absence of that stimulus.
      These neurons may be a substrate for adaptive responses that are necessary for
      behavioral modification.

PMID- 17004935
TI  - Effects of early life stress on adult male aggression and hypothalamic
      vasopressin and serotonin.
AB  - Early life stress in humans enhances the risk for psychopathologies, including
      excessive aggression and violence. In rodents, maternal separation is a potent
      early life stressor inducing long-lasting changes in emotional and neuroendocrine
      responsiveness to stress, associated with depression- and anxiety-like symptoms.
      However, effects of maternal separation on adult male aggression and underlying
      neurobiological mechanisms remain unknown. Therefore, we investigated the effects
      of maternal separation on adult intermale aggression in Wistar rats and on
      hypothalamic arginine vasopressin (AVP) mRNA expression, and AVP and serotonin (5
      HT) immunoreactivity, as both AVP and 5-HT have been implicated in stress-coping
      and aggression. We showed that maternal separation induced depression-like
      behaviour (increased immobility) and higher adrenocorticotropin hormone responses
      to an acute stressor (forced swimming). Intermale aggression (lateral threat,
      offensive upright and keep down) was significantly higher in maternally separated
      rats compared with control rats. AVP mRNA expression and AVP immunoreactivity
      were higher in the hypothalamic paraventricular and supraoptic nuclei upon
      resident-intruder test exposure, whereas 5-HT immunoreactivity was decreased in
      the anterior hypothalamus of maternally separated rats. Moreover, 5-HT
      immunoreactivity in the anterior hypothalamus and supraoptic nucleus correlated
      negatively with aggression. These findings show that exposure to early life
      stress increases adult male aggression in an animal model of maternal separation.
      Furthermore, the maternal separation-induced changes in hypothalamic AVP and 5-HT
      systems may underlie these behavioural alterations.

PMID- 17004936
TI  - Neurokinin receptor antagonism attenuates cocaine's behavioural activating
      effects yet potentiates its dopamine-enhancing action in the nucleus accumbens
      core.
AB  - Several lines of evidence indicate a role for neurokinin3 receptors (NK3-Rs) in
      behavioural activation and mechanisms governing reinforcement processes. In this
      study we investigated the effect of pretreatment with the NK3-R antagonist,
      SR142801, (0.2 and 2.0 mg/kg) on the cocaine-induced (10.0 mg/kg i.p.) increase
      in extracellular dopaminergic activity in the nucleus accumbens (NAc). In vivo
      microdialysis in the NAc of freely moving rats showed that cocaine increased
      concentrations of dopamine (DA) to approximately 350% in the core and
      approximately 450% in the shell. Pre-treatment with SR142801 significantly
      potentiated this effect in the core (to approximately 550%), whereas this effect
      was not found in the shell. We also investigated the effects of NK3-Rs antagonism
      on cocaine-induced hyperactivity and conditioned place preference. SR142801
      blocked the hyperactivity, but neither the conditioned place preference nor the
      conditioned locomotor activity induced by cocaine, although there was a slight
      tendency towards a reduced place preference. When given alone, SR142801 had no
      effects on behaviour or extracellular dopamine concentrations in any of the
      structures investigated. These data provide evidence for a contribution of NK3-Rs
      in the acute behavioural and neurochemical effects of cocaine, involving
      dopaminergic activity in the core of the nucleus accumbens.

PMID- 17004937
TI  - Cocaine withdrawal enhances long-term potentiation induced by corticotropin
      releasing factor at central amygdala glutamatergic synapses via CRF, NMDA
      receptors and PKA.
AB  - Cocaine addiction is an enduring, relapsing, behavioural disorder in which
      stressors reinstate cocaine-seeking even after prolonged abstinence. Evidence
      suggests that the 'anxiety-like' behaviour and stress associated with protracted
      withdrawal may be mediated by increased corticotropin-releasing factor (CRF) in
      the central nucleus of the amygdala (CeA), a part of the limbic circuitry engaged
      in the coding and transmission of stimulus-reward associations. In the present
      study we describe a long-lasting potentiation of glutamatergic transmission
      induced at lateral amygdala (LA)-to-CeA synapses by rat/human CRF. After 2 weeks
      of withdrawal from repeated intermittent exposure to cocaine, CRF-induced long
      term potentiation (LTP) was greatly enhanced compared to the respective saline
      control group while, after short-term withdrawal (24 h), there was no significant
      difference between the two treatment groups, indicating alterations in CRF
      systems during protracted withdrawal from chronic cocaine. After prolonged
      withdrawal, CRF-induced LTP was dependent on activation of CRF2, CaV2.3 (R-type)
      calcium channels and intracellular signalling through protein kinase C in both
      saline- and cocaine-treated groups. The enhanced CRF-induced LTP after 2 weeks of
      withdrawal was mediated through augmented CRF1 receptor function, associated with
      an increased signalling through protein kinase A, and required N-methyl-D
      aspartate (NMDA) receptors. Accordingly, single-cell recordings revealed a
      significantly increased NMDA/AMPA ratio after prolonged withdrawal from the
      cocaine treatment. These results support a role for CRF1 receptor antagonists as
      plausible treatment options during withdrawal from chronic cocaine and suggest
      Ca(V)2.3 blockers as potential candidates for pharmaceutical modulation of CRF
      systems.

PMID- 17004938
TI  - Smoking and structural brain deficits: a volumetric MR investigation.
AB  - Growing evidence from animal studies indicates brain-damaging properties of
      nicotine exposure. Investigations in humans found a wide range of functional
      cerebral effects of nicotine and cigarette smoking, but studies focusing on brain
      damage are sparse. In 22 smokers and 23 never-smokers possible differences of the
      cerebral structures were investigated using magnetic resonance imaging and voxel
      based morphometry. Significantly smaller grey matter volume and lower grey matter
      density (P = 0.05, corrected) were observed in the frontal regions (anterior
      cingulate, prefrontal and orbitofrontal cortex), the occipital lobe and the
      temporal lobe including parahippocampal gyrus, in smokers than in never-smokers.
      Group differences of either grey matter volume or grey matter density were also
      found in the thalamus, cerebellum and substantia nigra, among other regions.
      Smokers did not show greater volumes than never-smokers in any cerebral region.
      Magnitude of lifetime exposure to tobacco smoke (pack-years) was inversely
      correlated with volume of frontal and temporal lobes and cerebellum (P = 0.001,
      uncorrected). The data indicate structural deficits of several cortical and
      subcortical regions in smokers relative to never-smokers. The topographic profile
      of the group differences show some similarities to brain networks known to
      mediate drug reinforcement, attention and working memory processing. The present
      findings may explain in part the frequently reported cognitive dysfunctions in
      chronic cigarette consumers.

PMID- 17004939
TI  - Inactivation of the ventromedial prefrontal cortex reduces expression of
      conditioned fear and impairs subsequent recall of extinction.
AB  - Anxiety disorders are thought to reflect deficits in the regulation of fear
      expression. Evidence from rodent studies implicates the ventromedial prefrontal
      cortex (vmPFC) in the regulation of conditioned fear. Lesions of the vmPFC have
      had differing effects on the acquisition and expression of conditioned fear, as
      well as on recall of extinction. The use of permanent lesions, however, makes it
      difficult to assess the phase of training in which the vmPFC is acting and can
      trigger recruitment of other structures, thereby masking lesion deficits. To
      overcome these problems, we temporarily inactivated the vmPFC of rats with
      tetrodotoxin (10 ng in a 0.5-microl midline infusion) at one of four time points:
      prior to conditioning, prior to extinction, immediately after extinction or prior
      to recall of extinction. Consistent with lesion findings, inactivation of the
      vmPFC prior to acquisition had no effect but inactivation prior to extinction led
      to impaired recall of extinction the following day. In contrast to lesion
      findings, inactivation of the vmPFC decreased freezing at all time points,
      suggesting that some component of the vmPFC facilitates the expression of
      conditioned fear. These findings suggest that inactivation of the vmPFC can have
      opposite effects depending on the phase of training. The vmPFC appears to be
      involved both in stimulating the expression of conditioned fear and in serving as
      a site of extinction-related plasticity that inhibits fear during recall of
      extinction.

PMID- 17004940
TI  - CA3 NMDA receptors are crucial for rapid and automatic representation of context
      memory.
AB  - It is argued that the hippocampus contributes to acquisition of context-specific
      memory although neural mechanisms have not been clarified. To evaluate the role
      of CA3 in context-specific memory, we developed one-trial context discrimination
      tasks to test acquisition and retrieval of contextual memory in CA3 pyramidal
      cell-restricted N-methyl-d-aspartate (NMDA) receptor knockout mice. Mutants were
      unable to discriminate conditioned and no-shock contexts 3 h after one-trial
      avoidance training. These phenotypes were not evident 24 h after one-trial
      training or 3 h after multi-trial training. Following one-trial contextual fear
      conditioning, mutants showed a selective deficit in context discrimination during
      a retention test 3 h after acquisition, although overall freezing levels were
      similar to those of the control mice. As in the avoidance task, this context
      discrimination impairment was not observed 24 h after initial conditioning.
      Interestingly, extending the post-shock period to 3 min during the one-trial fear
      conditioning task eliminated the discrimination deficit observed at the 3 h
      retention interval. These results suggest that: (i) impaired rapid context
      discrimination during the recall test is dependent on the duration of post-shock
      period during conditioning; (ii) CA3 NMDA receptors are critically involved in
      rapid and automatic formation of a unified context memory representation from the
      sensory information; (iii) CA3 NMDA receptors support contextual pattern
      separation; (iv) fear memory to foot-shock is acquired without CA3 NMDA
      receptors. It appears that rapid and automatic context memory representations
      from one-time experience are mediated, at least in part, by CA3 NMDA receptors.

PMID- 17004941
TI  - The importance of the rat hippocampus for learning the structure of visual
      arrays.
AB  - It has been assumed that the integrity of the rodent hippocampus is required for
      learning the spatial distribution of visual elements in an array. Formally
      assessing this assumption is, however, far from straightforward as standard tests
      are amenable to alternative strategies. In order to provide a stringent test of
      this ability rats were trained on three concurrent visual discriminations in a
      water tank in which the stimuli in each pair of discriminations contained exactly
      the same elements but they differed in their spatial arrangement e.g. A|B vs. its
      mirror image B/A. Such 'structural' discriminations are a specific subtype of
      'configural' or 'nonlinear' tasks. Following acquisition half of the rats
      received hippocampal lesions and all rats were retrained on the structural
      discriminations. Hippocampal lesions impaired the ability to relearn these
      'structural' discriminations. In contrast, two other groups of rats with similar
      hippocampal lesions showed no impairment on relearning two non-structural,
      configural discriminations: transverse patterning and biconditional learning. All
      three tasks used the same apparatus, the same stimulus elements, and similar
      training regimes. Superior performance by the rats with hippocampal lesions
      during a generalization decrement probe showed that hippocampal lesions had
      diminished sensitivity to 'structural' features on the biconditional task. While
      the rat hippocampus need not be required for all configural learning, it is
      important for the special case when the spatial arrangements of the elements are
      critical. This ability may be a prerequisite for the creation of mental
      snapshots, which underlie episodic memory.

PMID- 17004942
TI  - A double dissociation of dorsal and ventral hippocampal function on a learning
      and memory task mediated by the dorso-lateral striatum.
AB  - The objectives of this research were to further delineate the neural circuits
      subserving proposed memory-based behavioural subsystems in the hippocampal
      formation. These studies were guided by anatomical evidence showing a
      topographical organization of the hippocampal formation. Briefly, perpendicular
      to the medial/lateral entorhinal cortex division there is a second system of
      parallel circuits that separates the dorsal and ventral hippocampus. Recent work
      from this laboratory has provided evidence that the hippocampus incidentally
      encodes a context-specific inhibitory association during acquisition of a visual
      discrimination task. One question that emerges from this dataset is whether the
      dorsal or ventral hippocampus makes a unique contribution to this newly described
      function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were
      assessed on the acquisition of the visual discrimination task. Following
      asymptotic performance they were given reversal training in either the same or a
      different context from the original training. The results showed that the context
      specific inhibition effect is mediated by a circuit that includes the ventral but
      not the dorsal hippocampus. Results from a control procedure showed that rats
      with either dorso-lateral striatum damage or dorsal hippocampal lesions were
      impaired on a tactile/spatial discrimination. Taken together, the results
      represent a double dissociation of learning and memory function between the
      ventral and dorsal hippocampus. The formation of an incidental inhibitory
      association was dependent on ventral but not dorsal hippocampal circuitry, and
      the opposite dependence was found for the spatial component of a tactile/spatial
      discrimination.

PMID- 17004943
TI  - Chronic high-frequency stimulation of the subthalamic nucleus and L-DOPA
      treatment in experimental parkinsonism: effects on motor behaviour and striatal
      glutamate transmission.
AB  - Hyperactivity of striatal glutamatergic synaptic transmission in response to
      dopamine depletion plays a major role in the pathogenesis of parkinsonian motor
      symptoms. In the present study we investigated the impact, on this hyperactivity,
      of chronic dyskinesiogenic L-DOPA treatment, combined or not with high-frequency
      stimulation (HFS) of the subthalamic nucleus (STN). In vitro patch-clamp
      recordings were performed from striatal spiny neurons of hemiparkinsonian rats
      (intranigral 6-OHDA injection). Here we show that dyskinesiogenic L-DOPA
      treatment exacerbated striatal glutamatergic hyperactivity induced by 6-OHDA
      lesion. Chronic 5-day STN HFS had the opposite effect, reducing striatal
      glutamatergic transmission in both parkinsonian and dyskinetic animals.
      Consistently, chronic HFS stimulation could progressively ameliorate motor
      parkinsonian signs (akinesia) but, conversely, did not improve L-DOPA-induced
      dyskinesia (LID). Thus, the effects of L-DOPA and HFS on corticostriatal
      transmission seem to be dissociated. These data show for the first time that
      dyskinesiogenic L-DOPA treatment and chronic STN HFS with antiakinetic effects
      induce opposite plastic rearrangements in the striatum. The interaction between
      these two treatments provides further evidence that striatal glutamatergic
      hyperactivity is a pathophysiological correlate of akinesia rather than LID.

PMID- 17004944
TI  - Marked alterations in the gait timing and rhythmicity of patients with de novo
      Parkinson's disease.
AB  - Little is known about the gait characteristics of subjects with de novo
      Parkinson's disease (PD). We hypothesized that alterations in the spatio-temporal
      characteristics of gait will already be quantifiable in these patients. The gait
      of 35 patients with idiopathic PD (mean age 60 years) who were in the early
      stages of the disease (Hoehn and Yahr stage 1.8 +/- 0.5, median 2.0, range 1.0
      2.5) and were not yet treated with any anti-parkinsonian medications were
      compared with the gait of age- and sex-matched healthy controls (n = 22). The
      patients walked more slowly and with reduced swing times while also exhibiting
      increased left/right swing asymmetry and marked inconsistencies in the timing of
      gait. By contrast, significant group differences in the peak forces at heel
      strike and in the stride-to-stride variability of the ground reaction forces (a
      reflection of muscle output consistency) were not observed. These findings
      indicate that in de novo PD, an altered gait pattern is observed, even though
      dramatic changes in the gait pattern may not yet be apparent visually (e.g.
      fairly intact gait speed). Furthermore, the results demonstrate that the observed
      alterations are not just side-effects of treatments or complications of the
      disease. Instead, there is evidence for motor programming deficits in gait, as
      revealed by increased gait variability and asymmetry in timing. PD apparently
      impinges on the regulation of a consistent gait rhythm, even early in the course
      of the disease when observed alterations are not the result of any pharmacologic
      treatment.

PMID- 17004945
TI  - Retinotopic distribution of chromatic responses in human primary visual cortex.
AB  - In non-human primates at least three anatomically and functionally distinct
      channels convey signals from the retina to the primary visual cortex (V1). Two of
      these channels, the parvocellular and the koniocellular, are sensitive to
      chromatic contrasts and form the basis of color vision. In humans, common
      phylogenetic history with other primates and psychophysical experiments suggest
      identical retinocortical mechanisms but separate evaluation of the distinct
      anatomical channels has been difficult because signals are already combined in
      V1. We studied the spatial distribution of activation to chromatic stimuli along
      the two opponent chromatic axes in human V1 with multifocal functional magnetic
      resonance imaging. The signal strength was quantified from three experiments with
      stimuli up to 20 degrees eccentricity. The hypothesis was that, although the
      parvo- and koniocellular signals are mixed in V1, distinct distributions of
      signal strength would be evident. We found that whereas different conditions
      activated the same areas of cortex, indicating that they have identical
      magnification factors, the responses to red/green stimulation were stronger close
      to the fovea whereas the blue/yellow responses were much less diminished with
      increasing eccentricity. Both chromatic axes showed saturating contrast response
      functions. Our measure directly from human V1 is in line with earlier
      psychophysical studies suggesting relatively stronger parvocellular channel
      representation close to the fovea, and more uniform distribution of the
      koniocellular and achromatic channels. In addition, our study presents a way to
      rapidly quantify retinotopic signal transmission in distinct retinocortical
      pathways of individual subjects.

PMID- 17004946
TI  - Specialization of the specialized in features of external human brain morphology.
AB  - Recent studies have shown brain differences between professional musicians and
      non-musicians with respect to size, asymmetry or gray matter density of specific
      cerebral regions. Here we demonstrate: (1) that anatomical differences in the
      motor cortex can already be detected by coarse visual inspection; and (2) that
      within musicians, even a discrimination of instruments with different manual
      dominance is possible on a gross anatomical scale. Multiple raters, blinded for
      subject identity and hemisphere, investigated within-musician differences in the
      Omega Sign (OS), an anatomical landmark of the precentral gyrus associated with
      hand movement representation. The sample of 64 brains comprised matched groups of
      16 expert string-players, 16 expert pianists and 32 non-musicians. Ratings were
      analysed by means of kappa statistics. Intra- and interobserver reliabilities
      were high. Musicians had a more pronounced OS expression than non-musicians, with
      keyboard-players showing a left and string-players a right hemisphere advantage.
      This suggests a differential brain adaptation depending on instrument played.

PMID- 17004947
TI  - Neural responses to silent lipreading in normal hearing male and female subjects.
AB  - In the past, researchers investigated silent lipreading in normal hearing
      subjects with functional neuroimaging tools and showed how the brain processes
      visual stimuli that are normally accompanied by an auditory counterpart.
      Previously, we showed activation differences between males and females in primary
      auditory cortex during silent lipreading, i.e. only the female group
      significantly activated the primary auditory region during lipreading. Here we
      report and discuss the overall activation pattern in males and females. We used
      positron emission tomography to study silent lipreading in 19 normal hearing
      subjects (nine females). Prior to scanning, subjects were tested on their
      lipreading ability and only good lipreaders were included in the study. Silent
      lipreading was compared with a static image. In the whole group, activations were
      found mainly in the left hemisphere with major clusters in superior temporal,
      inferior parietal, inferior frontal and precentral regions. The female group
      showed more clusters and these clusters were larger than in the male group. Sex
      differences were found mainly in right inferior frontal and left inferior
      parietal regions and to a lesser extent in bilateral angular and precentral gyri.
      The sex differences in the parietal multimodal region support our previous
      hypothesis that the male and female brain process visual speech stimuli
      differently without differences in overt lipreading ability. Specifically,
      females associate the visual speech image with the corresponding auditory speech
      sound whereas males focus more on the visual image itself.

PMID- 17004949
TI  - Idiopathic epilepsy in dogs: owners' perspectives on management with
      phenobarbitone and/or potassium bromide.
AB  - OBJECTIVES: To explore seizure management from the perspective of the owners of
      dogs with idiopathic epilepsy. METHODS: Questionnaires were mailed to owners of
      29 dogs under management for suspected or diagnosed idiopathic epilepsy through
      the clinics of the Small Animal Hospital of the University of Glasgow Veterinary
      School, using either phenobarbitone or potassium bromide alone or in combination.
      RESULTS: The postal survey had an 86 per cent response rate. Analysis of the
      responses demonstrated that "the dog's quality of life", "adequate seizure
      frequency" and "acceptable side effects of antiepileptic drugs" were the three
      greatest concerns for owners; 52 per cent of owners strongly agreed that the
      seizure management for their dog was adequate, though the seizure frequency
      reported varied within this group; the majority of owners did not consider the
      administration of medication a nuisance. However, approximately 60 per cent of
      owners reported that caring for an epileptic dog had an effect on the
      organisation of their free time, though this was not dependent on perception of
      seizure control. Opinions as to the value of further diagnostic procedures, in
      particular intracranial imaging, were significantly affected by having pet health
      insurance. CLINICAL SIGNIFICANCE: From the owners' perspective, adequacy of
      seizure control is determined by the balance between "the dog's quality of life",
      "adequate seizure frequency" and "acceptable side effects of antiepileptic
      drugs". A frequency of less than one seizure every three months is associated
      with the perception by owners of adequate seizure control.

PMID- 17004950
TI  - Canine neurological diseases in a referral hospital population between 1989 and
      2000 in Switzerland.
AB  - OBJECTIVES: To merge clinical information from partly overlapping medical record
      databases of the Small Animal Teaching Hospital of the Vetsuisse Faculty,
      University of Berne. To describe the frequencies and localisations of
      neurological diseases in dogs, as well as their age, gender, breed and
      geographical distributions. METHODS: In this retrospective study, a new database,
      with specific variables and a diagnosis key list 'VITAMIN D', was created and
      defined. A total of 4497 dogs (average of 375 per year) with a well-documented
      neurological disease were included in the study. A key list for the diagnoses was
      developed and applied to either the presumptive or the clinical and
      neurohistopathological diagnosis, with a serial number, a code for localisation
      and a code for differential diagnoses. RESULTS: Approximately 1159 dogs (26 per
      cent) had a neurohistopathological diagnosis confirmed, 1431 (32 per cent) had a
      clinical diagnosis confirmed and 1491 (33 per cent) had a presumptive diagnosis.
      The most frequent breeds were mixed-breed dogs (577 of 4497, 13 per cent),
      followed by German shepherd dogs (466 of 4497, 10 per cent). The most common
      localisations were the forebrain (908 of 4497, 20 per cent) and the spinal cord
      at the thoracolumbar area (840 of 4497, 19 per cent). Most dogs were diagnosed
      with degenerative diseases (38 per cent), followed by inflammatory/infectious
      diseases (14 per cent). The highest number of submissions originated from
      geographic regions around the referral hospital and from regions with higher
      human population densities. CLINICAL SIGNIFICANCE: By defining closed-list fields
      and allocating all data to the corresponding fields, a standardised database that
      can be used for further studies was generated. The analysis of this study gives
      examples of the possible uses of a standardised database.

PMID- 17004951
TI  - Combined cytosine arabinoside and prednisone therapy for meningoencephalitis of
      unknown aetiology in 10 dogs.
AB  - OBJECTIVES: The differential diagnosis for young to middle-aged dogs with
      progressive neurological signs, focal or multifocal computed tomography/magnetic
      resonance imaging lesions, mononuclear cerebrospinal fluid pleocytosis and
      negative infectious titres includes granulomatous meningoencephalomyelitis, breed
      specific meningoencephalitis, infectious meningoencephalitis of unknown origin
      and central nervous system neoplasia. The terminology meningoencephalitis of
      unknown aetiology may be preferable for cases that lack histopathological
      diagnoses. The safety and efficacy of a combination of cytosine arabinoside and
      prednisone protocol is evaluated, in this study, for the treatment of
      meningoencephalitis of unknown aetiology in 10 dogs. METHODS: Cases were selected
      based on neuroanatomical localisation, negative regional infectious disease
      titres, cerebrospinal fluid pleocytosis and brain imaging. Clinical response was
      gauged through follow-up examinations, owner and referring veterinarian surveys
      and review of medical records. RESULTS: Partial or complete remission was
      achieved in all dogs; the median survival time for the 10 dogs was 531 days
      (range 46 to 1025 days), with five of the 10 dogs alive at the time of writing.
      CLINICAL SIGNIFICANCE: Prednisone/cytosine arabinoside is a safe empirical
      therapy for dogs with meningoencephalitis of unknown aetiology; this drug
      combination may prolong survival time.

PMID- 17004952
TI  - Meningoencephalitis associated with Staphylococcus warneri in a dog.
AB  - A case of meningoencephalitis in a dog caused by Staphylococcus warneri is
      reported here. The history and clinical signs were suggestive of possible central
      nervous system infection. Analysis of cerebrospinal fluid documented a
      neutrophilic pleocytosis (890 cells/mul) and the presence of occasional
      intracellular cocci. Staphylococcus warneri was isolated from the microbiological
      culture of the cerebrospinal fluid. Treatment consisted of intravenous
      antibiotics, supportive care and anticonvulsants for the generalised seizures
      that developed after admission. Histological assessment confirmed the location
      and extension of bacterial meningoencephalitis. Thrombotic meningoencephalitis
      associated with Staphylococcus warneri infection has not, to the authors'
      knowledge, been previously reported in dogs.

PMID- 17004953
TI  - Coexistence of occipital dysplasia and occipital hypoplasia/syringomyelia in the
      cavalier King Charles spaniel.
AB  - Concurrent occurrence of occipital dysplasia and occipital hypoplasia in two dogs
      is described in this report. Occipital hypoplasia results in reduced volume of
      the caudal fossa, leading to overcrowding of the neural structures and, in severe
      cases, development of syringomyelia. In occipital dysplasia, there is a failure
      of complete ossification of the supraoccipital bone. When the two conditions
      occur concurrently, it is possible that syringomyelia may develop more slowly,
      resulting in presentation with clinical signs in middle to old age. This has
      implications for screening tests for early detection of syringomyelia, with a
      view to using the dog for breeding purposes, as dogs with an apparently mild
      phenotype for occipital hypoplasia/syringomyelia may actually have a more severe
      genotype.

PMID- 17004954
TI  - Primary and secondary tumours occurring simultaneously in the brain of a dog.
AB  - Primary brain tumours of a single histological type and metastatic brain tumours
      are well described in dogs in the current veterinary literature. However, the
      concurrent presence of a primary and secondary tumour in the brain of a dog has
      never, to the authors' knowledge, been previously reported. The clinical and
      pathological features of a nine-year-old, female boxer with an oligodendroglioma
      and metastases from a mammary gland adenocarcinoma occurring simultaneously in
      the brain are described in this case report. Information in the veterinary
      literature on multiple malignancies affecting the central nervous system is very
      limited; therefore, a discussion about comparative situations in human medicine
      has been included.

PMID- 17004955
TI  - Localised sarcoptic mange in dogs: a retrospective study of 10 cases.
AB  - The authors report 10 cases of localised sarcoptic mange in dogs. In each case,
      lesions were localised to one precise area of the skin. Pruritus was present in
      nine cases and absent in one. Affected areas were the feet (one case), the face
      and/or the pinnae (six cases), the abdominal skin (one case), the flank (one
      case) and the lumbar area (one case). The types of lesions were erythema,
      papules, lichenification, scales, crusts and alopecia. Parasites were found in
      all cases except one, in which anti-immunoglobulin G Sarcoptes serology was
      positive. The acaricidal treatments given were lindane, ivermectin or selamectin
      and were all successful.

PMID- 17004956
TI  - Swimmer syndrome in a Devon rex kitten and an English bulldog puppy.
AB  - A three-week-old Devon rex kitten and a four-week-old English bulldog puppy were
      presented with "swimmer syndrome". The owners consulted several veterinarians who
      suggested euthanasia as the only possible solution for this condition.
      Physiotherapy in the puppy, and physiotherapy and bandaging in the kitten led to
      the resolution of the clinical signs and resulted in normal ambulation after
      several weeks. The authors concluded that intensive physiotherapy and dedication
      of the owner can lead to success.

PMID- 17004957
TI  - Clinical presentation and management of moxidectin toxicity in two dogs.
AB  - Moxidectin is a macrocyclic lactone related to ivermectin used in horses and dogs
      for endoparasite treatment and prophylaxis. The clinical and neurological
      presentation of moxidectin toxicity in two dogs following inadvertent poisoning
      with a moxidectin-containing equine de-worming medication is reported here. In
      both the dogs, the predominant clinical signs were generalised tremors and
      ataxia. Moxidectin exerts its neurotoxic effects in mammals by potentiating the
      effect of gamma-aminobutyric acid and, consistent with this, both the dogs
      demonstrated a poor response to treatment with diazepam. It would be more
      appropriate to avoid gamma-aminobutyric acid agonists, such as benzodiazepines
      and barbiturates, in dogs with moxidectin toxicity and consider using anaesthetic
      agents with a different mode of action, such as propofol. The prognosis in dogs
      accidentally exposed to moxidectin-containing equine de-worming medication
      appears to be excellent if the cause of the neurotoxicity is correctly identified
      and the case is appropriately managed.

PMID- 17004958
TI  - What is your diagnosis? Vaginal oedema/hyperplasia or vaginal prolapse.

PMID- 17004959
TI  - Care pathways - the future's bright.

PMID- 17004960
TI  - National eCare Pathways Service (NeCPS).

PMID- 17004961
TI  - A decade on: has the use of integrated care pathways made a difference in
      Lanarkshire?
AB  - This article aimed to: (1) review the work carried out in Lanarkshire between
      1996 and 1999 on a Scottish Executive funded project and (2) to discuss the
      situation from 1999 to 2006. (1) This 3-year project led to the successful
      development and implementation of over 100 integrated care pathways in an urban
      teaching hospital (Glasgow) and a district general hospital (Lanarkshire) and was
      the first in-depth study of integrated care pathways to be undertaken in
      Scotland. The main report on the project was produced in 1999 (Clinical Audit and
      Quality using Integrated Pathways of Care) and reported increased adherence to
      British Thoracic Society and Scottish Intercollegiate Guidelines Network
      guidelines and multiple best practice statements, and improved standards of
      documentation. The general findings were that process indicators were improved by
      integrated care pathway use and there was some suggestion of improved length of
      stay with no apparent effect on outcome. Evidence was found that integrated care
      pathways have made a difference for both patients and staff. (2) This provides an
      update of integrated care pathway development in a changing environment within
      NHS Lanarkshire and examines some of the key factors for success.

PMID- 17004962
TI  - The development of an Integrated Care Pathway for all patients with advanced life
      limiting illness - the Supportive Care Pathway.
AB  - AIM: To describe the development and implementation of an Integrated Care Pathway
      for all patients with advanced life-limiting illness who have been admitted to
      hospital. BACKGROUND: This pathway, called the Supportive Care Pathway, has been
      developed not only in response to the national drivers to improve end of life
      care, but also in recognition of local survey data which demonstrated the need
      for strategies to support the provision of palliative care. The pathway is aimed
      primarily at generalist staff who may have a significant number of patients with
      palliative care needs on their wards, though not necessarily yet in the last days
      of life. METHOD: The pathway, which is being piloted on three elderly care wards
      in the West Midlands, has been developed in line with accepted Integrated Care
      Pathway methodology and is being evaluated using the Integrated Care Pathways
      Assessment Tool. RESULTS: The pathway has been well received by staff using it
      and early evaluation of its effect in improving documentation of care is
      encouraging. CONCLUSIONS: Unacceptable variations in care for those nearing the
      end of life is recognized. It is believed that the use of the Supportive Care
      Pathway may help to reduce that variation by identifying and supporting patients
      thought to be in the last year of their life.

PMID- 17004963
TI  - Clinical pathway audit tools: a systematic review.
AB  - AIM: To determine whether clinical/care pathway audit tools can identify the
      characteristics of well-organized care processes. BACKGROUND: Although pathways
      are used worldwide, confusion exists about the concept and impact. Evaluation
      Search of OVID-Medline, Cinahl, British Nursing Index; manual search of the
      Journal of Integrated Care Pathways; contact with Smartgroup on Clinical Pathways
      and board members of the European Pathway Association and Google search. KEY
      ISSUES: We selected seven of 15 clinical pathway audit tools for this review.
      Through content analysis, we identified 17 characteristics and grouped them using
      the realistic evaluation paradigm. The Integrated Care Pathway Appraisal Tool is
      the most appropriate audit tool to assess clinical pathway documents.
      CONCLUSIONS: It is astonishing that so little research on clinical pathway audit
      tools has been underwent, given the prevalent use of clinical pathways. Because
      the concept of clinical pathways remains unclear, a variety of audit tools are
      needed to help clarify the concept. Further research on the construct and
      criterion validity of pathway audit tools is necessary to fully understand why
      and under which circumstances pathways lead to improved care.

PMID- 17004964
TI  - Care pathways in obstetrics: the effectiveness in reducing the incidence of
      episiotomy in childbirth.
AB  - AIM: To develop a care pathway for childbirth. BACKGROUND: Care pathways are
      emerging as an effective tool to improve clinical and organizational performance.
      METHODS: A pre- and postimplementation analysis model was used to evaluate the
      effect of introducing a care pathway for childbirth. Key outcome indicators and
      costs were reviewed to compare the traditional care processes with those of the
      care pathway. The study involved 380 women. RESULTS: There was a significant
      reduction in episiotomy rate (from 14.90% to 8.6%, P = 0.02) in patients being
      cared for using a care pathway approach; however, there were no differences in
      caesarean section and in perineal wound rates. The average costs per patient on
      the care pathway were euro 1278.42 ( pound 873.64) compared with euro 1,146.87 (
      pound 783.74) preimplementation. The study also demon- strated an increase in
      patient satisfaction for women cared for using the care pathway approach.
      CONCLUSIONS: The care pathway proved to be a valid methodological approach to
      childbirth, allowing healthcare workers to efficiently share the care of the
      women, guaranteeing safe and effective care.

PMID- 17004965
TI  - What is protocol-based care? A concept analysis.
AB  - AIM: To define protocol-based care to make this way of delivering health care
      amenable to theoretical and empirical studies. BACKGROUND: Although protocol
      based care is associated with the evidence-based practice and standardization
      movements, it is an ill-defined and understood concept. METHOD: A multiphase
      concept analysis, inspired by an evolutionary view was used to clarify 'what is
      protocol-based care'. The inductive, five-phase process drew upon content
      analysis of policy documents and the literature, plus interviews with a purposive
      sample of 35 opinion leaders. RESULTS: The term was used interchangeably with
      protocols, pathways and guidelines in policy and guidance documents. A search of
      seven databases produced only 57 references to protocol-based care. The concept
      analysis revealed a continuum of scope and specificity and also distinguished
      specialist and generic applications of protocol-based care. CONCLUSIONS: Managers
      need to take cognizance of the significance and complexity of protocol-based care
      when introducing this way of working.

PMID- 17004966
TI  - Defining pathways.
AB  - AIMS AND BACKGROUND: The term 'clinical pathway' is internationally accepted in
      all settings of healthcare management. The way in which clinical pathways have
      been developed in the United Kingdom differs from that in the USA. Besides the
      international differences in the purpose, many alternative names also can be
      found. These have led to confusion. There is no single, widely accepted
      definition of a clinical pathway. The aim of the study was to survey the
      definitions used in describing the concept and to derive key characteristics of
      clinical pathways. METHOD: Using the PubMed, we conducted a review of literature
      published between January 2000 and December 2003 using the following terms:
      critical pathway, clinical pathway, integrated care pathway, care pathway and
      care map. All reports reviewed had to use the concept, as defined by the Medical
      Subject Headings term, to be considered. To assess all definitions, the concept
      analysis method was used. RESULTS: In 82 of the 263 eligible articles, the
      definition of pathway was given. Totally, we found 84 different definitions. Each
      definition was rephrased by taking into consideration the following three
      features inherent to pathways: nouns, characteristics and aims and outcomes.
      Every feature was further divided into categories. CONCLUSIONS: A clinical
      pathway is a method for the patient-care management of a well-defined group of
      patients during a well-defined period of time. A clinical pathway explicitly
      states the goals and key elements of care based on Evidence Based Medicine (EBM)
      guidelines, best practice and patient expectations by facilitating the
      communication, coordinating roles and sequencing the activities of the
      multidisciplinary care team, patients and their relatives; by documenting,
      monitoring and evaluating variances; and by providing the necessary resources and
      outcomes. The aim of a clinical pathway is to improve the quality of care, reduce
      risks, increase patient satisfaction and increase the efficiency in the use of
      resources.

PMID- 17004967
TI  - A pilot project to design, implement and evaluate an electronic integrated care
      pathway.
AB  - The project focused on the design, implementation and evaluation of an electronic
      integrated care pathway (eICP), within a Mother and Baby Unit. Health care
      professionals and service users (stakeholders) were involved in the process in
      order to promote patient centred, co-constructed care. Questionnaire and
      discussion groups were used for data collection regarding the initial eICP
      development. Of 15 participants who took part in the design and development of
      the eICP, seven were able to take part in the evaluation process on the Unit.
      Results show that 100% (n = 7) of the participants were in agreement with the
      eICP and the format that was produced and implemented for trial on the Unit.
      Increased ownership of records, greater multi disciplinary involvement and
      enhanced patient experience were also reported. Recommendations for clinical
      practice include resource management, ownership of the research group, holism
      maintenance and the acquisition of computer skills.

PMID- 17004969
TI  - Modulation of ABH histo-blood group antigen expression in normal and myasthenic
      human thymus.
AB  - The role of ABH histo-blood group antigens (HBGA) in intercellular communication
      during normal and pathological processes is still uncertain. The present work
      investigates the expression of ABH HBGA in epithelial cells and lymphocytes in
      normal thymus, and characterizes the modulation of their immunoreactivity during
      myasthenic transformation. Immunohistochemistry and immunoelectron microscopy
      were applied on normal young thymus and on myasthenia gravis-associated thymomas
      and thymic hyperplasias. The Hassall's corpuscules in the thymus of young
      individuals were homogeneously stained for HBGA, while in hyperplastic glands
      only their central part was positive. Stromal epithelial cells permanently
      expressed HBGA in all tissue samples. In thymomas, mainly the lymphocytes in
      close proximity to antigen expressing epithelial cells were positive, while in
      the hyperplastic gland the most intensely stained lymphocytes were those within
      Hassall's corpuscules. Novel evidence for modulation of ABH antigen reactivity in
      normal and myasthenic human thymus is presented. It suggests that HBGA might
      participate in the regulation of the cross-talk in the thymocyte microenvironment
      throughout the ontogeny, as well as during the myasthenic transformation.

PMID- 17004970
TI  - Prognostic value of plasma soluble urokinase plasminogen activator receptor
      (suPAR) in Danish patients with recurrent epithelial ovarian cancer (REOC).
AB  - The level of the soluble urokinase plasminogen activator receptor (suPAR) is
      elevated in tumour tissue from several types of cancer. This is the first study
      aiming to predict the prognosis for survival by the use of a pre-chemotherapeutic
      plasma suPAR value in 71 patients with recurrent epithelial ovarian cancer
      (REOC). For determination of suPAR, pre-chemotherapeutic blood samples from the
      patients with REOC were processed into plasma (EDTA) within one working day from
      venipuncture. The plasma suPAR level is not correlated with performance status
      (p=0.41), FIGO stage (p=0.09), treatment-free interval (TFI) of 12 months
      (p=0.26), site of recurrence (peritoneum, p=0.50 or pelvis, p=0.44), age
      (p=0.43), or serum CA125 (p=0.09). Univariate as well as multivariate analyses
      cannot demonstrate that high pre-chemotherapeutic levels of plasma suPAR (p=0.22,
      p=0.80) are associated with shorter survival of REOC patients. Multivariate
      analysis showed that only TFI of 12 months (p=0.001) and performance score status
      of 2 (p=0.02) were independent prognostic factors. Our study indicates that pre
      chemotherapeutic measurement of plasma suPAR level in REOC patients may not be
      useful to identify a subgroup of patients with poor prognosis.

PMID- 17004971
TI  - Pulmonary cryptosporidiosis: role of COX2 and NF-kB.
AB  - In the present study we investigated whether the pathological changes induced by
      Cryptosporidium in the lungs are mediated through the activation of COX-2, and
      whether the pathway employed for this activation involves NF-kB. 70 albino rats
      were submitted for this work. They were categorized into 3 groups: 30
      immunocompetent (IC) rats infected with Cryptosporidium oocysts, 30
      immunosuppressed (IS) rats infected with Cryptosporidium oocysts, and 10 IC, non
      infected rats. Immunohistochemical expression of COX2 and NF-kB in lung tissues
      of the rats was examined. 43.3% of IC rats showed chronic pneumonia and fibrosis,
      40% COX2 positivity, and 36.67% NF-kB positivity. 96.7% of IS rats showed chronic
      pneumonia and fibrosis, 56.7% non-caseating granuloma with Cryptosporidium
      oocysts, and 66.7% positivity for both COX2 and NF-kB. Density of inflammatory
      infiltration was statistically correlated with quickscore of both COX2 and NF-kB
      in both IC and IS groups. An association between quickscores of COX2 and NF-kB
      was found in our studied material. These data could demonstrate that
      Cryptosporidium infection induces upregulation of COX2 possibly through the NF-kB
      pathway, which suggests the events that contribute to the pathogenesis of
      Cryptosporidium. These findings could indicate potential therapeutic
      pharmacological target-mediating treatment of lesions caused by Cryptosporidium.

PMID- 17004972
TI  - Immune response in rhesus macaques after mixed modality immunisations with DNA,
      recombinant adenovirus and recombinant gp120 from human immunodeficiency virus
      type 1.
AB  - The establishment of effective regimens for a vaccine against human
      immunodeficiency virus type 1 (HIV-1) is urgently needed. In the present study we
      have produced HIV-1 gp120 from a vaccine-relevant primary R5 isolate in
      recombinant vaccinia (rVV)-infected Vero cells. We have investigated the effect
      of boosting with this protein in mixed modality immunisations of rhesus macaques
      following different immunisation. As reported earlier, animals were primed with
      codon-optimised HIV-1(BX08)env DNA delivered as plasmid or as replication
      deficient recombinant human adenovirus type 5 (rAd5), which both induced specific
      antibody and cellular immune responses (1). Boosting with rAd5 temporarily had
      increased the anti-gp120 antibody titres approximately 1 log (rAd5+rAd5) or 3 log
      (DNA+rAd5) (1). However, secondary rAd5 boosting showed less effect due to the
      induced vector-specific immunity. To further boost the antibody response, the
      rgp120(BX08) was injected with Quadri A saponin adjuvant. The protein boosting
      resulted in a 1-2 log antibody increase and also boosting of the cell-mediated
      immune response. Neutralising antibodies to the heterologous HIV-1(MN) were
      detected; however, neutralising antibodies to the primary HIV-1(Bx08) isolate
      were seen only transiently after rAd5 but not the rgp120 immunisation. It is
      concluded that the rgp120(Bx08) reagent from rVV-infected Vero cells is
      functional and immunogenic in macaques, inducing both antibody and cellular
      immunity. The rgp120(Bx08) is a relevant model antigen that may be used to boost
      antibody and cellular immunity in mixed modality vaccine regimens against HIV-1
      in higher animals.

PMID- 17004973
TI  - Glomerular C3c deposition and intravascular macrophage accumulation in early
      humoral renal allograft rejection signifies a poor short-term outcome.
AB  - C4d deposition in the walls of peritubular capillaries is considered the key
      phenomenon in the histopathological diagnosis of humoral, i.e. antibody-mediated,
      allograft rejection. We have earlier proposed that deposition of C3c in
      glomerular capillaries and simultaneous intravascular accumulation of macrophages
      in allografts with immediate or early humoral rejection indicates a potentially
      serious condition with very poor prognosis. The clinical outcome of 45 cadaveric
      grafts with this phenomenon among 1960 renal allografts transplanted at our
      centre during 1984-1999, and the recipients of the contralateral kidneys, was
      retrospectively evaluated. Graft failure occurred in 44/45 grafts within 3 weeks,
      with graft loss in 33/45 (77%) within 4 months and 37/45 (82%) within 1 year.
      From the contralateral kidneys, 5/33 (15%) were lost within 1 year. In a recent
      series of early biopsies, we recognised that of 13 cases showing C4d positivity
      in peritubular capillaries but lacking C3c in glomeruli, 10/13 (77%) were still
      functioning after 4 months. The mean number of CD68(+) macrophages per glomerular
      profile, i.e. the glomerular macrophage index, shows a significant difference
      between C4d(+)C3c(-) and C4d(+)C3c(+) cases (p<0.001). Our results indicate the
      existence of a clinically important subgroup of early humoral rejection with
      particular morphological features.

PMID- 17004974
TI  - Comparative study of monoclonal antibody B72.3 and gross cystic disease fluid
      protein-15 as markers of apocrine carcinoma of the breast.
AB  - Gross cystic disease fluid protein-15 (GCDFP-15) is a commonly used apocrine
      marker; however, its expression was recently found to decrease in infiltrating,
      larger, or metastasizing apocrine carcinomas of the breast. In the breast,
      monoclonal antibody (MAb) B72.3 has been reported to be useful as an apocrine
      marker although it is used for that purpose much less frequently than GCDFP-15.
      In the search for a more consistent apocrine marker, immunoreactivity for MAb
      B72.3 was examined in apocrine carcinomas at different stages and compared with
      GCDFP-15. 47 of 51 apocrine carcinomas (92%) and 9 of 62 ordinary carcinomas
      (15%) were MAb B72.3 positive, while 39 of 51 apocrine carcinomas (76%) and 13 of
      62 ordinary carcinomas (21%) were GCDFP-15 positive. Thus, both sensitivity and
      specificity were higher for MAb B72.3. Furthermore, unlike GCDFP-15, MAb B72.3
      exhibited positivity irrespective of infiltrating status, tumor size, or
      metastatic status. There was no correlation between MAb B72.3-immunoreactivity
      and GCDFP-15-expression. The combined usage of MAb B72.3 with GCDFP-15 was useful
      to confirm the diagnosis of apocrine carcinoma, especially for advanced tumors,
      with only two cases being negative for both MAb B72.3 and GCDFP-15. Whether these
      two cases should be differentiated from ordinary apocrine carcinomas remains to
      be investigated.

PMID- 17004975
TI  - Pancreatic endocrine tumor with partial acinar cell differentiation.
AB  - We examined a 70-year-old woman in whom a pancreatic endocrine tumor with partial
      acinar cell differentiation had been diagnosed. She had neither endocrine nor
      exocrine symptoms. The tumor was located in the pancreatic tail and measured 12.5
      x 9.5 x 8 cm. It had a capsule, was composed of multiple adhesion nodules, and
      was elastically soft, medullary, and yellowish white. The neoplastic cells had
      large, irregular, oval nuclei; prominent eosinophilic nucleoli; and abundant
      eosinophilic cytoplasm with many fine granules. The cells had proliferated in
      islet-like solid medullary, trabecular, acinar, and papillary patterns. Most
      neoplastic cells were strongly positive for synaptophysin. 10 to 25% of the
      neoplastic cells were positive for alpha1-antitrypsin. Neuroendocrine and zymogen
      granules were simultaneously observed in the cytoplasm of the same neoplastic
      cells at the ultrastructural level. The tumor may be considered an amphicrine
      tumor.

PMID- 17004976
TI  - Metastatic chordoma of the breast: an extremely rare lesion mimicking mucinous
      cancer.
AB  - Metastases in the breast are rare, with metastatic chordoma being one of the
      rarest. To our knowledge, only one such case has previously been published in the
      literature. We report a case of a 74-year-old woman who presented with a palpable
      lump in her right breast. The lump was mammographically suggestive of mucinous
      breast cancer because it was a solitary, small, circular, and moderately dense
      lesion yielding abundant mucoid aspirate. The tumor resembled mucinous carcinoma
      upon histologic and immunohistochemical examination: it had a mucinous stroma,
      and the tumor cells strongly expressed epithelial markers. However, the patient
      had previously undergone surgery for a recurrent sacral chordoma. In addition to
      the clinical history, the presence of typical physaliferous cells expressing
      neither estrogen receptors nor cytokeratin 7, but staining positively for S-100
      protein, allowed the proper diagnosis. Although extremely rare, metastatic
      chordoma may represent a challenge in the differential diagnosis of breast
      lesions. Discriminating metastases of mucin-producing tumors in the breast from
      primary mucinous carcinomas is important with regard to the striking difference
      in prognosis of these lesions.

PMID- 17004977
TI  - Combined treatment of pediatric high-grade glioma with the oncolytic viral strain
      MTH-68/H and oral valproic acid.
AB  - The case of a 12-year-old boy with anaplastic astrocytoma of the left thalamus is
      reported. Postoperative irradiation and chemotherapy could not repress tumor
      progression; therefore, treatment was undertaken with an oncolytic virus, MTH
      68/H, an attenuated strain of Newcastle disease virus (NDV), and valproic acid
      (VPA), an antiepileptic drug, which also has antineoplastic properties. This
      treatment resulted in a far-reaching regression of the thalamic glioma, but 4
      months later a new tumor manifestation, an extension of the thalamic tumor,
      appeared in the wall of the IVth ventricle, which required a second neurosurgical
      intervention. Under continuous MTH-68/H - VPA administration the thalamic tumor
      remained under control, but the rhombencephalic one progressed relentlessly and
      led to the fatal outcome. In the final stage, a third tumor manifestation
      appeared in the left temporal lobe. The possible reasons for the antagonistic
      behavior of the three manifestations of the same type of glioma to the initially
      most successful therapy are discussed. The comparative histological study of the
      thalamic and rhombencephalic tumor manifestations revealed that MTH-68/H
      treatment induces, similar to in vitro observations, a massive apoptotic tumor
      cell decline. In the rhombencephalic tumor, in and around the declining tumor
      cells, NDV antigen could be demonstrated immunohistochemically, and virus
      particles have been found in the cytoplasm of tumor cells at electron microscopic
      investigation. These findings document that the oncolytic effect of MTH-68/H
      treatment is the direct consequence of virus presence and replication in the
      neoplastic cells. This is the first demonstration of NDV constituents in an MTH
      68/H -treated glioma.

PMID- 17004978
TI  - Report of an angiosarcoma mimic: cutaneous aneurysmal fibrous histiocytoma.
AB  - Aneurysmal fibrous histiocytoma is an unusual variant of the spectrum of fibrous
      histiocytomas with the peculiar morphologic appearance of a benign aneurysmal
      vasoformative process that ultimately culminates in multiple microhemorrhages
      within the tumor. It looks strikingly different from the usual cutaneous lesions
      encountered in clinical dermatology practice. A single report of a cutaneous
      aneurysmal fibrous histiocytoma in the skin of the back of a 60-year-old male is
      described with emphasis on the immunostaining pattern and review of the
      literature. There is a significant potential for confusion of this lesion with
      other cutaneous lesions, clinically as well as pathologically. In our case, the
      patient presented with a lesion that clinically resembled a hemangioma, was
      pathologically interpreted initially to be an angiosarcoma, and finally, the
      revised pathology was interpreted as an aneurysmal variant of a fibrous
      histiocytoma. Caution is warranted to avoid misinterpretation of cutaneous
      fibrohistiocytic tumors.

PMID- 17004979
TI  - Combined effects of maternal smoking status and dietary intake related to weight
      gain and birth size parameters.
AB  - OBJECTIVE: To investigate the interaction of smoking status and dietary intake
      during pregnancy and its relationship to maternal weight gain and birth size
      parameters. DESIGN: An observational prospective study. SETTING: Free-living
      conditions. POPULATION: Four hundred and eight healthy pregnant Icelandic women.
      METHODS: Maternal smoking status, lifestyle factors and dietary habits were
      evaluated with questionnaires. Intake of foods and supplements was also estimated
      with a semiquantitative food frequency questionnaire for the previous 3 months.
      All questionnaires were filled out between 11 and 15 weeks and between 34 and 37
      weeks of gestation. Smoking status in relation to optimal and/or excessive weight
      gain during pregnancy was represented with logistic regression controlling for
      potential confounding factors. MAIN OUTCOME MEASURES: Maternal weight gain,
      smoking status, dietary intake and birthweight. RESULTS: Women who smoked
      throughout pregnancy were unlikely to gain optimal weight or more (OR 0.51, 95%
      CI 0.27-0.97), whereas smoking cessation in connection with pregnancy ('former
      smokers') doubled the risk of excessive weight gain (OR 2.03, 95% CI 1.24-3.35).
      The latter association was no longer significant after adjustment for dietary
      factors and other confounding factors. Former smokers ate the least amount of
      fruit and vegetables (fruit: 129 versus 180 and 144 g/day (median), P= 0.038;
      vegetables: 53 versus 76 and 72 g/day, P= 0.026 for former smokers, nonsmokers
      and smokers, respectively). Birthweight was lowest among infants born to smokers,
      but birthweight was similar for former smokers and nonsmokers (3583 +/- 491 g
      versus 3791 +/- 461 g and 3826 +/- 466 g, respectively; P= 0.003). CONCLUSIONS:
      Smoking cessation in early pregnancy or pre-pregnancy is not associated with low
      birthweight. It is, however, associated with excessive maternal weight gain and a
      low fruit and vegetable intake.

PMID- 17004980
TI  - Improving the accuracy of estimated blood loss at obstetric haemorrhage using
      clinical reconstructions.

PMID- 17004981
TI  - Glycaemic control throughout pregnancy and risk of pre-eclampsia in women with
      type I diabetes.
AB  - The aim of this study was to examine the influence of pre-pregnancy care and its
      effect on early glycaemic control and also the effect of glycaemic control in
      later pregnancy on risk of pre-eclampsia in women with type I diabetes. A
      prospective cohort study of 290 consecutive nonselected pregnancies in women with
      type I diabetes was performed from 1991 to 2002. We examined the relationship of
      monthly glycosylated haemoglobin (HbA1c) level, pre-pregnancy care, parity,
      diabetes duration, microvascular complications, maternal age, weight and smoking
      with risk of pre-eclampsia. Pre-eclampsia developed in 31/243 singleton births
      (12.8%). HbA1c level at 24 weeks was significantly increased in women with pre
      eclampsia compared with women without pre-eclampsia (6.0 versus 5.6%, P= 0.017)
      and was, after nulliparity, the strongest independent predictor of increased risk
      (OR 1.65 for each 1% increase in HbA1c; P= 0.01). In contrast, there was no
      relationship between pre-pregnancy care or HbA1c level at booking and risk of pre
      eclampsia.

PMID- 17004983
TI  - Anterior cervical hypertrichosis (hairy throat): is it a sign to worry about?

PMID- 17004982
TI  - Intravenous versus oral iron therapy for postpartum anaemia.
AB  - OBJECTIVE: Postpartum iron deficiency anaemia (IDA) is common in women. Most
      women are treated with either oral iron supplementation or blood transfusion.
      Hence, the aim of our study was to compare the effect of treatment with either
      oral ferrous sulphate or intravenous ferrous sucrose on postpartum IDA. DESIGN: A
      single centre, prospective randomised controlled trial. SETTING: Women's Centre,
      John Radcliffe Hospital, Oxford, UK. POPULATION: Forty-four women with
      haemoglobin (Hb) of <9 g/dl and ferritin of <15 microgram/l at 24-48 hours
      postdelivery. METHODS: Women were randomised to receive either oral ferrous
      sulphate 200 mg twice daily for 6 weeks (group O) or intravenous ferrous sucrose
      200 mg (Venofer; Vifor International Ltd, St Gallen, Switzerland), two doses
      given on days 2 and 4 following recruitment (group I). RESULTS: were analysed by
      the Students t-test, chi-square test and analysis of variance. MAIN OUTCOME
      MEASURES: Hb, haematocrit, red cell indices, ferritin and serum iron levels were
      measured on days 0, 5, 14 and 40. Results By day 5, the Hb level in women treated
      with intravenous iron had risen from 7.3 +/- 0.9 to 9.9 +/- 0.7 g/dl, while there
      was no change in those treated with oral iron. Women treated with intravenous
      iron had significantly higher Hb levels on days 5 and 14 (P < 0.01) than those
      treated with oral iron; although by day 40, there was no significant difference
      between the two groups. Throughout the study, ferritin levels rose rapidly in
      those treated with intravenous iron and remained significantly higher than in
      those treated with oral iron (P < 0.01). CONCLUSIONS: Intravenous iron sucrose
      increases the Hb level more rapidly than oral ferrous sulphate in women with
      postpartum IDA. It also appears to replenish iron stores more rapidly. However,
      this study was not large enough to address the safety of this strategy.

PMID- 17004984
TI  - B-cell targeted therapy alone may not be effective in bullous pemphigoid.

PMID- 17004985
TI  - Eccrine porocarcinoma and Bowen's disease arising in a seborrhoeic keratosis.
AB  - An association between seborrhoeic keratosis (SK) and malignant tumours is
      considered to be rare. We observed a case of eccrine porocarcinoma and Bowen's
      disease (BD) occurring synchronously, forming one lesion in a SK on the abdomen.
      It is controversial whether malignant neoplasms arising in SK occur only by
      chance or if pre-existing SK plays a role in pathogenesis. This case suggests an
      implication of pre-existing SK in the subsequent development of both BD and
      eccrine porocarcinoma.

PMID- 17004986
TI  - Acute generalized exanthematous pustulosis associated with azathioprine
      hypersensitivity.
AB  - Acute generalized exanthematous pustulosis (AGEP) is identified by several
      characteristic features. We present a patient showing AGEP associated with
      azathioprine hypersensitivity. To our knowledge, this is the first reported case
      of this association.

PMID- 17004987
TI  - Topical immunotherapy with diphenylcyclopropenone in the treatment of chronic
      extensive alopecia areata.
AB  - Highly variable results have been described for the use of topical
      diphenylcyclopropenone (DPCP) in the treatment of alopecia areata (AA). We
      enrolled 41 patients in a prospective open clinical trial. Of these, 17 patients
      had either AA totalis (AAT) or AA universalis (AAU), and 24 had severe alopecia
      (> 50% scalp involvement). After sensitization with DPCP 2% in acetone,
      progressively higher concentrations were applied once a week for a period of 6-12
      months. Of the 41 patients, 38 (16 with AAT or AAU and 22 with extensive AA)
      completed therapy. Significant hair regrowth was observed in 15 of the 38
      patients (39.5%) at 6 months: 5 with AAT or AAU (31.25%) and 10 with extensive
      alopecia (45.4%). The above results were sustained in 66.6% of patients for a 12
      month-follow up- period. In our study, topical immunotherapy with DPCP proved to
      be an effective treatment, with prolonged therapeutic results.

PMID- 17004988
TI  - Localized reactive angioendotheliomatosis.
AB  - We present a unique case of a woman with multiple painful dermal lesions
      localized to the left upper quadrant of the body. Histological investigation
      revealed microvascular thrombosis with capillary-wall proliferation. Further
      investigation revealed a very high anticardiolipin IgG titre and a left
      subclavian stenosis, presumably providing the reduced blood flow and relative
      hypoxia to allow microthromboses to occur in the presence of a thrombophilic
      tendency. Similar clinical and histological features have been reported in
      patients with the antiphospholipid syndrome and cases of reactive
      angioendotheliomatosis (RAE). This case represents a unique variant of RAE.

PMID- 17004989
TI  - Successful treatment of lichen amyloidosis with combined bath PUVA
      photochemotherapy and oral acitretin.
AB  - Lichen amyloidosis (LA) is a chronic, pruritic skin disorder characterized by
      brownish-grey papules on extensor surfaces of legs and rarely on the trunk.
      Thioflavin T-positive amyloid deposits are found in the papillary dermis of
      affected skin, which is the only organ involved. A variety of therapeutic
      regimens for lichen amyloidosis have been described; however, in many cases with
      only limited effect. We report on two patients with lichen amyloidosis with
      typical clinical symptoms not responding to local treatment. A combined regimen
      with bath psoralen ultraviolet A (PUVA) and oral acitretin was initiated,
      resulting in nearly complete resolution of the papules and impressive relief from
      the severe pruritus. The beneficial response has persisted for 8 months. The
      suggested combined therapy with bath PUVA photochemotherapy and oral acitretin
      represents an efficacious and practical treatment modality for lichen amyloidosis
      with long-lasting effects.

PMID- 17004990
TI  - Which children should we patch test?
AB  - BACKGROUND: Allergic contact dermatitis (ACD) in childhood was considered rare
      until recently. However, reports are increasing, which may reflect an increased
      incidence and/or more frequent patch testing of children. It is also likely that
      allergen exposure in children has changed with time. AIMS: To determine the most
      common contact allergens and the rate of positive patch-test reactions among
      children with suspected contact allergy. METHODS: We carried out a retrospective
      case study of 114 children (66 girls and 48 boys) aged from 3 to 15 years (median
      11.5) patch tested over a 3-year period. Indications for patch testing included
      uncontrolled or deteriorating atopic dermatitis, localized dermatitis or a
      history of reacting to a specific allergen. RESULTS: Of 110 children for whom we
      had notes, 83 (75%) had a history of atopy. Positive reactions that were of
      current, past or possible relevance were seen in 61 children (54%); in 58 (52%)
      of 111 tested with the standard series (SS) and in 6 (10%) of 60 tested with the
      medicament series. None of the children patch tested to the corticosteroid (n =
      47), shoe (n = 15), fragrance (n = 12), cosmetic (n = 10) or rubber (n = 5)
      series had a positive reaction. However, 11 (10%) reacted to rubber allergens
      within the SS and one of five to their own shoes. The lowest rate of relevant
      positive reactions was among those with deteriorating atopic dermatitis (22%) and
      facial (33%) or perioral dermatitis (40%), and the highest rate amongst those
      with eyelid (86%) or hand (71%) dermatitis. Nickel was the most common allergen
      (20%) in line with previous reports (82% female), followed by rubber chemicals
      (10%), fragrance (7.2%), cobalt (5.4%) and lanolin (wool alcohol) (4.5%).
      CONCLUSIONS: The reported incidence of ACD among children, in particular nickel
      and rubber allergy, appears to be increasing, which may relate to changing
      fashions and hobbies. Contact allergy should be considered in all children with
      dermatitis, particularly with eyelid or hand dermatitis, and patch testing
      carried out more frequently.

PMID- 17004991
TI  - From gamma-carboxy-glutamate to protein C.
AB  - The story I shall recount started in 1969, when I was given the opportunity to
      join the Department of Clinical Chemistry at the University Hospital in Malmo. I
      had just finished medical school at the university in the neighboring town of
      Lund. Parallel to pursuing my medical studies I had spent some time in the
      Department of Biochemistry. I did not know much about biochemistry, but it was
      enough for me to realize that I wanted to do laboratory research rather than
      developing a clinical career. I was happy to accept an offer to start working in
      the laboratory, particularly as the head of the department, Professor Carl-Bertil
      Laurell, had an excellent reputation. As it turned out, I came to spend almost
      all of my professional life in the laboratory.

PMID- 17004992
TI  - Toll-like receptor 9 acts at an early stage in host defence against pneumococcal
      infection.
AB  - Toll-like receptor 9 (TLR9) induces an inflammatory response by recognition of
      unmethylated CpG dinucleotides, mainly present in prokaryotic DNA. So far, TLR9
      deficient mice have been shown to be more sensitive than wild-type mice to viral,
      but not to bacterial infections. Here, we show that mice deficient in TLR9 but
      not in TLR1, TLR2, TLR4 and TLR6 or IL-1R/IL-18R are more susceptible to a
      respiratory tract bacterial infection caused by Streptococcus pneumoniae.
      Intranasal challenge studies revealed that TLR9 plays a protective role in the
      lungs at an early stage of infection prior to the entry of circulating
      inflammatory cells. Alveolar as well as bone marrow-derived macrophages deficient
      in either TLR9 or the myeloid adaptor differentiation protein MyD88 were impaired
      in pneumococcal uptake and in pneumococcal killing. Our data suggest that in the
      airways, pneumococcal infection triggers a TLR9 and MyD88-dependent activation of
      phagocytic activity from resident macrophages leading to an early clearance of
      bacteria from the lower respiratory tract.

PMID- 17004993
TI  - Application of 16S rRNA gene-targetted fluorescence in situ hybridization and
      restriction fragment length polymorphism to study porcine microbiota along the
      gastrointestinal tract in response to different sources of dietary fibre.
AB  - A total of 32 pigs of 15+/-0.38 kg body weight were fed for 6 weeks one of four
      diets differing in their source of dietary fibre. FISH was used to quantify the
      main bacterial groups in the pig gut using the following probes: Eub338, Bac303,
      Rfla729, Rbro730, Erec482, Fprau645, Prop853, Str493 and Lab158. FISH counts
      revealed important differences at four sites along the pig gastrointestinal
      tract, but we were unable to show differences related to diets. Stomach and
      jejunal samples gave total bacterial counts of 0.1-5.3 x 10(8) g(-1) of contents.
      In the stomach, streptococci and lactobacilli were predominant, and the
      clostridial cluster IX group was abundant (14-41% of total bacterial count).
      Clostridial cluster IX bacteria were present elsewhere in the gastrointestinal
      tract at 1-8%. The other groups were generally more abundant in the proximal
      colon and rectum: Bacteroides/Prevotella (5-10%), clostridial cluster XIVa (10
      19%), and cluster IV relatives of Faecalibacterium prausnitzii (1-4%) and
      ruminococcus (4-10%). Restriction fragment length polymorphism profiles showed
      changes related to diet, with pigs fed wheat bran having the lowest richness of
      all diets (P=0.008).

PMID- 17004995
TI  - Pediatric rosacea.
AB  - Rosacea is a condition most commonly associated with adults; however, various
      forms exist in the pediatric population and need to be considered when a child
      presents with a facial rash. Acne rosacea, steroid rosacea, granulomatous
      periorificial dermatitis, and other variants of rosacea are presented here and
      are distinguished from their numerous mimickers. Various topical and systemic
      therapeutic options exist for the treatment of rosacea with several adjustments
      and considerations that must be taken into account when treating a child.

PMID- 17004996
TI  - Childhood acne: evaluation and management.
AB  - Acne is a disease that can be seen in the first year of life, early childhood,
      prepubertal age, and puberty. The purpose of this article is to review the
      clinical presentation and pathogenesis of the various forms of prepubertal acne
      and to propose guidelines regarding its evaluation and treatment. The early
      clinical recognition of the disease and prompt initiation of therapy in these age
      groups will help prevent the sequelae of emotional distress and severe scarring
      in both the child and parents.

PMID- 17004997
TI  - Diagnosis and management of the dermatologic manifestations of the polycystic
      ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex phenotypic spectrum of primarily
      hyperandrogenic signs and symptoms. PCOS is the most common endocrine disturbance
      to affect women of reproductive years. Although patients affected are often very
      disturbed by the cutaneous manifestations, including acne, hirsutism, alopecia,
      obesity, and acanthosis nigricans, the clinical manifestations of PCOS ramify far
      beyond the skin. PCOS frequently causes menstrual abnormalities and infertility.
      Insulin resistance is both pathogenic and a cause of numerous serious health
      consequences. The accurate diagnosis and recognition of cutaneous
      hyperandrogenism in PCOS are discussed. The differential diagnosis is reviewed.
      The work-up and approach to evaluation of patients with PCOS is presented.
      Although no uniform treatment approach for the management of the cutaneous
      manifestations of PCOS has been agreed upon, the data on various treatment
      options and the author's treatment approach to these patients are presented.

PMID- 17004998
TI  - Tricks for improving compliance with acne therapy.
AB  - Adherence to a medical regimen is the most important aspect of therapeutic
      efficacy. It goes without saying that a drug that is not used will not be
      effective. Reasons for noncompliance can be related to the specific disease
      state, to characteristics of the drugs chosen, to patient personality traits, and
      to effectiveness of the clinician in dealing with the individual patient.
      Recognizing, confronting, and improving noncompliant behavior are all part of an
      effective doctor-patient relationship.

PMID- 17004999
TI  - Psychological problems in the acne patient.
AB  - Acne is a ubiquitous affliction that can leave physical and emotional scars that
      can persist throughout the life of the affected individual. Recent studies have
      substantiated the psychological impact and support a causal, and at times
      reciprocal, link between acne and the emotional and functional status of the
      patient. The present article will examine the recent data substantiating the
      emotional and functional impact of acne on the affected individual. Criteria to
      identify high-risk patients are provided. High-risk patients are those at
      increased risk for psychological and functional impairment or self-injurious
      behavior.

PMID- 17005000
TI  - Coping with the isotretinoin registry.
AB  - The isotretinoin registry has arrived. It has a lofty goal of preventing all
      isotretinoin pregnancies. How we got to this point and what the registry means to
      prescribers and patients have many dermatologists confused and concerned. Will it
      be burdensome, will it preclude the use in most offices of this most important
      drug? Will it breed a new group of "isotretinologists" who are willing to take on
      the challenge? This article endeavors to answer these questions and to put most
      concerns at rest. The new system seems ultimately to have few changes compared to
      the risk management program we are already (technically) following. The
      difference is that compliance with all the rules will be monitored and mandatory.
      The system seems user friendly, is accessible to the computer-savvy as well as
      those of us still addicted to telephone, and may well turn out to be much fuss
      made over minimal hassle. What is clear is that this is likely our last chance to
      save this wonderful drug from oblivion. It is time for dermatologists to step to
      the plate and do what is in the best interest of their patients.

PMID- 17005001
TI  - Physiological behaviour of Saccharomyces cerevisiae in aerated fed-batch
      fermentation for high level production of bioethanol.
AB  - Saccharomyces cerevisiae was able to produce 20% (v/v) of ethanol in 45 h in a
      fully aerated fed-batch process recently developed in our laboratory. A notable
      feature of this process was a production phase uncoupled to growth, the extent of
      which was critical for high-level ethanol production. As the level of production
      was found to be highly variable, we investigated on this high variability by
      means of a detailed physiological analysis of yeast cells in two fed-batch
      fermentations showing the most extreme behaviour. We found a massive leakage of
      intracellular metabolites into the growth medium which correlated with the drop
      of cell viability. The loss of viability was also found to be proportional to the
      reduction of plasma membrane phospholipids. Finally, the fed-batch processes with
      the longest uncoupling phase were characterized by induction of storage
      carbohydrates at the onset of this phase, whereas this metabolic event was not
      seen in processes with a short uncoupling phase. Taken together, our results
      suggested that reproducible high-level bioethanol production in aerated fed-batch
      processes may be linked to the ability of yeast cells to impede ethanol toxicity
      by triggering a metabolic remodelling reminiscent to that of cells entering a
      quiescent GO/G1 state.

PMID- 17005002
TI  - Splice variants of human FOXP3 are functional inhibitors of human CD4+ T-cell
      activation.
AB  - FOXP3 has been identified as a key regulator of immune homeostasis. Mutations
      within the FOXP3 gene result in dysregulated CD4+ T-cell function and elevated
      cytokine production, leading to lymphoproliferative disease. FOXP3 expression in
      CD4+ T cells is primarily detected with the CD4+ CD25+ regulatory T-cell
      population. In humans the protein is detected as a doublet following immunoblot
      analysis. The lower band of the doublet has been identified as a splice isoform
      lacking a region corresponding to exon 2. The aim of this study was to
      investigate whether the splice variant form lacking exon 2 and a new novel splice
      variant lacking both exons 2 and 7, were functional inhibitors of CD4+ T-cell
      activation. The data generated showed that full-length FOXP3 and both splice
      variant forms of the protein were functional repressors of CD4+ T-cell
      activation.

PMID- 17005003
TI  - Mycobacteria lacking the RD1 region do not induce necrosis in the lungs of mice
      lacking interferon-gamma.
AB  - The genetic region of difference 1 (RD1) in Mycobacterium tuberculosis has
      recently been hypothesized to encode for proteins that are cytotoxic to the host
      cell in nature. We demonstrate here that while M. tuberculosis grew progressively
      in the lungs of gene disrupted mice (GKO) unable to produce interferon-gamma (IFN
      gamma), similar mice infected instead with M. bovis bacillus Calmette-Guerin
      (BCG) reproducibly exhibited an obvious slowing of the disease after about 20
      days. Closer examination of BCG-infected GKO mice showed a florid granulomatous
      inflammation in the lungs, whereas similar mice infected with M. tuberculosis
      exhibited wholesale progressive necrosis. In the BCG-infected GKO mice large
      numbers of activated effector T cells, some strongly positive for the cytokine
      tumour necrosis factor, as well as activated natural killer cells accumulated in
      the lungs. To further test the hypothesis that the differences observed were
      directly associated with the loss of the RD1 region, it was then shown that a
      mutant of M. tuberculosis lacking RD1 grew progressively in both normal and GKO
      mice but failed to induce any degree of necrosis in either animal despite
      reaching similar levels in the lungs. However, when mice were infected with this
      mutant, in which the RD1 region had been restored by complementation, wholesale
      necrosis of the lungs again occurred. These data support the hypothesis that
      proteins encoded in the RD1 region are a major cause of necrosis and contribute
      significantly to the pathogenesis of the disease.

PMID- 17005004
TI  - Prolonged exposure of naive CD8+ T cells to interleukin-7 or interleukin-15
      stimulates proliferation without differentiation or loss of telomere length.
AB  - Interleukin (IL)-7 and IL-15 are cytokines implicated in homeostatic control of
      the peripheral CD8 T-cell pool. We compared the effects of IL-7 and IL-15 on
      survival and proliferation of purified human CD8+ T-cell subsets. Low
      concentrations of either cytokine reduced the spontaneous apoptosis of all
      subsets, and enhancement of survival corresponded to the extent of Bcl-2 up
      regulation. Surprisingly, although minimal proliferation of naive CD8+ T cells
      was observed during the first week of culture with cytokines, a marked expansion
      of these cells occurred at later time points, particularly in response to IL-15.
      This occurred largely without phenotypic change or acquisition of effector
      function, indicating a dissociation of differentiation from proliferation.
      Notably, progression of naive CD8+ T cells through several cell divisions
      resulted in up-regulation of telomerase and the maintenance of telomere length.
      These data show that IL-7 and IL-15 induce cell proliferation and rescue from
      apoptosis in a concentration, time and subset-dependent manner, and have
      implications for the homeostatic expansion of the naive CD8+ T-cell pool.

PMID- 17005005
TI  - Cancer immunosuppression and autoimmune disease: beyond immunosuppressive
      networks for tumour immunity.
AB  - Cancer immunosuppression evolves by constitution of an immunosuppressive network
      extending from a primary tumour site to secondary lymphoid organs and peripheral
      vessels and is mediated by several tumour-derived soluble factors (TDSFs) such as
      interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta) and vascular
      endothelial growth factor (VEGF). TDSFs induce immature myeloid cells and
      regulatory T cells in accordance with tumour progression, resulting in the
      inhibition of dendritic cell maturation and T-cell activation in a tumour
      specific immune response. Tumour cells grow by exploiting a pro-inflammatory
      situation in the tumour microenvironment, whereas immune cells are regulated by
      TDSFs during anti-inflammatory situations--mediated by impaired clearance of
      apoptotic cells--that cause the release of IL-10, TGF-beta, and prostaglandin E2
      (PGE2) by macrophages. Accumulation of impaired apoptotic cells induces anti-DNA
      antibodies directed against self antigens, which resembles a pseudo-autoimmune
      status. Systemic lupus erythematosus is a prototype of autoimmune disease that is
      characterized by defective tolerance of self antigens, the presence of anti-DNA
      antibodies and a pro-inflammatory response. The anti-DNA antibodies can be
      produced by impaired clearance of apoptotic cells, which is the result of a
      hereditary deficiency of complements C1q, C3 and C4, which are involved in the
      recognition of phagocytosis by macrophages. Thus, it is likely that impaired
      clearance of apoptotic cells is able to provoke different types of immune
      dysfunction in cancer and autoimmune disease in which some are similar and others
      are critically different. This review discusses a comparison of immunological
      dysfunctions in cancer and autoimmune disease with the aim of exploring new
      insights beyond cancer immunosuppression in tumour immunity.

PMID- 17005006
TI  - No evidence for the use of DIR, D-D fusions, chromosome 15 open reading frames or
      VH replacement in the peripheral repertoire was found on application of an
      improved algorithm, JointML, to 6329 human immunoglobulin H rearrangements.
AB  - Antibody diversity is created by imprecise joining of the variability (V),
      diversity (D) and joining (J) gene segments of the heavy and light chain loci.
      Analysis of rearrangements is complicated by somatic hypermutations and
      uncertainty concerning the sources of gene segments and the precise way in which
      they recombine. It has been suggested that D genes with irregular recombination
      signal sequences (DIR) and chromosome 15 open reading frames (OR15) can replace
      conventional D genes, that two D genes or inverted D genes may be used and that
      the repertoire can be further diversified by heavy chain V gene (VH) replacement.
      Safe conclusions require large, well-defined sequence samples and algorithms
      minimizing stochastic assignment of segments. Two computer programs were
      developed for analysis of heavy chain joints. JointHMM is a profile hidden Markow
      model, while JointML is a maximum-likelihood-based method taking the lengths of
      the joint and the mutational status of the VH gene into account. The programs
      were applied to a set of 6329 clonally unrelated rearrangements. A conventional D
      gene was found in 80% of unmutated sequences and 64% of mutated sequences, while
      D-gene assignment was kept below 5% in artificial (randomly permutated)
      rearrangements. No evidence for the use of DIR, OR15, multiple D genes or VH
      replacements was found, while inverted D genes were used in less than 1 per
      thousand of the sequences. JointML was shown to have a higher predictive
      performance for D-gene assignment in mutated and unmutated sequences than four
      other publicly available programs. An online version 1.0 of JointML is available
      at http://www.cbs.dtu.dk/services/VDJsolver.

PMID- 17005007
TI  - Novel modular enzymes encoded by a cellulase gene cluster in Cellvibrio mixtus.
AB  - Hydrolysis of plant cell wall polysaccharides, a process which is of intrinsic
      biological and biotechnological importance, requires the concerted action of an
      extensive repertoire of microbial cellulases and hemicellulases. Here, we report
      the identification of the gene cluster unk16A, regA and cel5B in the aerobic soil
      bacterium Cellvibrio mixtus, encoding a family 16 (CmUnk16A) glycoside hydrolase
      (GH), an AraC/XylS transcription activator (CmRegA) and a family 5 (CmCel5B) endo
      glucanase, respectively. CmUnk16A is a modular enzyme comprising, in addition to
      the catalytic domain, two family 32 carbohydrate-binding modules (CBMs), termed
      CBM32-1 and CBM32-2, a CBM4 and a domain of unknown function. We show that CBM32
      2 binds weakly to laminarin and pustulan. CmRegA is also a modular protein
      containing a highly hydrophobic N-terminal domain and a C-terminal DNA-binding
      domain of the AraC/XylS family. The role of the identified enzymes in the
      hydrolysis of cell wall polysaccharides by aerobic bacteria is discussed.

PMID- 17005008
TI  - Linkage of avian and reproductive tract tropism with sequence divergence adjacent
      to the 5S ribosomal subunit rrfH of Salmonella enterica.
AB  - The 183 bp between the end of the 23S rrlH rRNA gene and the start of the 5S rrfH
      rRNA gene (ISR-1) and the 197 bp between the end of the rrfH rRNA gene and the
      start of the transfer RNA aspU (ISR-2) of Salmonella enterica ssp. enterica
      serotypes Enteritidis, Typhimurium, Pullorum, Heidelberg, Gallinarum, Typhi and
      Choleraesuis were compared. ISR-1s of D1 serotypes (Pullorum, Gallinarum and
      Enteritidis), B serotypes (Typhimurium and Heidelberg) and the C2 serotype
      Newport and the enteric fever pathogens serotype A Paratyphi and serotype D1
      Typhi formed three clades, respectively. ISR-2 further differentiated the avian
      adapted serotype Gallinarum from avian-adapted Pullorum and Salmonella bongori
      from S. enterica. The results suggest that serotypes Heidelberg and Choleraesuis
      share some evolutionary trends with egg-contaminating serotypes. In addition, ISR
      1 and ISR-2 sequences that confirm serotype appear to be linked to clinically
      relevant host associations of the Salmonellae.

PMID- 17005010
TI  - Sec16 defines endoplasmic reticulum exit sites and is required for secretory
      cargo export in mammalian cells.
AB  - The selective export of proteins and lipids from the endoplasmic reticulum (ER)
      is mediated by the coat protein complex II (COPII) that assembles onto the ER
      membrane. In higher eukaryotes, COPII proteins assemble at discrete sites on the
      membrane known as ER exit sites (ERES). Here, we identify Sec16 as the protein
      that defines ERES in mammalian cells. Sec16 localizes to ERES independent of
      Sec23/24 and Sec13/31. Overexpression, and to a lesser extent, small interfering
      RNA depletion of Sec16, both inhibit ER-to-Golgi transport suggesting that Sec16
      is required in stoichiometric amounts. Sar1 activity is required to maintain the
      localization of Sec16 at discrete locations on the ER membrane, probably through
      preventing its dissociation. Our data suggest that Sar1-GTP-dependent assembly of
      Sec16 on the ER membrane forms an organized scaffold defining an ERES.

PMID- 17005011
TI  - The genetics and genomics of the drought response in Populus.
AB  - The genetic nature of tree adaptation to drought stress was examined by utilizing
      variation in the drought response of a full-sib second generation (F(2)) mapping
      population from a cross between Populus trichocarpa (93-968) and P. deltoides
      Bart (ILL-129) and known to be highly divergent for a vast range of phenotypic
      traits. We combined phenotyping, quantitative trait loci (QTL) analysis and
      microarray experiments to demonstrate that 'genetical genomics' can be used to
      provide information on adaptation at the species level. The grandparents and F(2)
      population were subjected to soil drying, and contrasting responses to drought
      across genotypes, including leaf coloration, expansion and abscission, were
      observed, and QTL for these traits mapped. A subset of extreme genotypes
      exhibiting extreme sensitivity and insensitivity to drought on the basis of leaf
      abscission were defined, and microarray experiments conducted on these genotypes
      and the grandparent species. The extreme genotype groups induced a different set
      of genes: 215 and 125 genes differed in their expression response between groups
      in control and drought, respectively, suggesting species adaptation at the gene
      expression level. Co-location of differentially expressed genes with drought
      specific and drought-responsive QTLs was examined, and these may represent
      candidate genes contributing to the variation in drought response.

PMID- 17005012
TI  - Characterization of CidR-mediated regulation in Bacillus anthracis reveals a
      previously undetected role of S-layer proteins as murein hydrolases.
AB  - Recent studies have shown that the Staphylococcus aureus cidABC and lrgAB operons
      are involved in the regulation of cell death and lysis. The transcription of
      cidABC and lrgAB was shown to be induced by acetic acid and was dependent on the
      cidR gene encoding a new member of the LysR-type transcription regulator (LTTR)
      family of proteins. In the study presented here, we examined the phenotypic and
      regulatory effects of disrupting a cidR homologue in Bacillus anthracis. As in S.
      aureus, the cidR mutation affected expression of the B. anthracis cid and lrg
      homologues, murein hydrolase activity and cell viability in stationary phase.
      Interestingly, the predominant murein hydrolase affected was an 85 kDa protein
      that was identified as Sap, a primary constituent of the S-layer in B. anthracis.
      The ability of Sap, as well as its counterpart EA1, to exhibit murein hydrolase
      activity was confirmed by cloning their respective genes in Escherichia coli and
      showing that the overexpressed proteins contained this activity. Northern blot
      analyses revealed that the cidR mutation caused reduced transcription of the
      genes encoding Sap and EA1, as well as CsaB involved in the attachment of the S
      layer proteins to the cell wall. The results of these studies not only establish
      the existence of the cid and lrg murein hydrolase regulatory network in B.
      anthracis, but also help to define the function and regulation of the S-layer
      proteins.

PMID- 17005013
TI  - Regulation of cytotoxin expression by converging eukaryotic-type and two
      component signalling mechanisms in Streptococcus agalactiae.
AB  - Signal transducing mechanisms are essential for regulation of gene expression in
      both prokaryotic and eukaryotic organisms. Regulation of gene expression in
      eukaryotes is accomplished by serine/threonine and tyrosine kinases and cognate
      phosphatases. In contrast, gene expression in prokaryotes is controlled by two
      component systems that comprise a sensor histidine kinase and a cognate DNA
      binding response regulator. Pathogenic bacteria utilize two-component systems to
      regulate expression of their virulence factors and for adaptive responses to the
      external environment. We have previously shown that the human pathogen
      Streptococcus agalactiae (Group B Streptococci, GBS) encodes a single eukaryotic
      type serine/threonine kinase Stk1, which is important for virulence of the
      organism. In this study, we aimed to understand how Stk1 contributes to virulence
      of GBS. Our results indicate that Stk1 expression is important for resistance of
      GBS to human blood, neutrophils and oxidative stress. Consistent with these
      observations, Stk1 positively regulates transcription of a cytotoxin, beta
      haemolysin/cytolysin (beta-H/C) that is critical for survival of GBS in the
      bloodstream and for resistance to oxidative stress. Interestingly, positive
      regulation of beta-H/C by Stk1 requires the two-component regulator CovR.
      Further, we show that Stk1 can negatively regulate transcription of CAMP factor
      in a CovR-dependent manner. As Stk1 phosphorylates CovR in vitro, these data
      suggest that serine/threonine phosphorylation impacts CovR-mediated regulation of
      GBS gene expression. In summary, our studies provide novel information that a
      eukaryotic-type serine/threonine kinase regulates two-component-mediated
      expression of GBS cytotoxins.

PMID- 17005014
TI  - Bipolar localization of the group II intron Ll.LtrB is maintained in Escherichia
      coli deficient in nucleoid condensation, chromosome partitioning and DNA
      replication.
AB  - Group II introns are mobile genetic elements that invade their cognate intron
      minus alleles via an RNA intermediate, in a process known as retrohoming. They
      can also retrotranspose to ectopic sites at low frequency. In Escherichia coli,
      retrotransposition of the lactococcal group II intron, Ll.LtrB, occurs
      preferentially within the Ori and Ter macrodomains of the E. coli chromosome.
      These macrodomains migrate towards the poles of the cell, where the intron
      encoded protein, LtrA, localizes. Here we investigate whether alteration of
      nucleoid condensation, chromosome partitioning and replication affect
      retrotransposition frequencies, as well as bipolar localization of the Ll.LtrB
      intron integration and LtrA distribution in E. coli. We thus examined these
      properties in the absence of the nucleoid-associated proteins H-NS, StpA and
      MukB, in variants of partitioning functions including the centromere-like
      sequence migS and the actin homologue MreB, as well as in the replication mutants
      DeltaoriC, seqA, tus and topoIV (ts). Although there were some dramatic
      fluctuations in retrotransposition levels in these hosts, bipolar localization of
      integration events was maintained. LtrA was consistently found in nucleoid-free
      regions, with its localization to the cellular poles being largely preserved in
      these hosts. Together, these results suggest that bipolar localization of group
      II intron retrotransposition results from the residence of the intron-encoded
      protein at the poles of the cell.

PMID- 17005015
TI  - Regeneration, tissue injury and the immune response.
AB  - The involvement of the immune system in the response to tissue injury has raised
      the possibility that it might influence tissue, organ or appendage regeneration
      following injury. One hypothesis that has been discussed is that inflammatory
      aspects may preclude the occurrence of regeneration, but there is also evidence
      for more positive roles of immune components. The vertebrate eye is an
      immunoprivileged site where inflammatory aspects are inhibited by several
      immunomodulatory mechanisms. In various newt species the ocular tissues such as
      the lens are regenerative and it has recently been shown that the response to
      local injury of the lens involves activation of antigen-presenting cells which
      traffic to the spleen and return to displace and engulf the lens, thereby
      inducing regeneration from the dorsal iris. The activation of thrombin from
      prothrombin in the dorsal iris is one aspect of the injury response that is
      important in the initiation of regeneration. The possible relationships between
      the immune response and the regenerative response are considered with respect to
      phylogenetic variation of regeneration in general, and lens regeneration in
      particular.

PMID- 17005016
TI  - How to build and rebuild a lens.
AB  - Evolution has used many different strategies to build eyes and lenses. However,
      the genetic regulation involved seems to be quite conserved. Likewise, the
      regeneration of eye structures is remarkable, especially in salamanders. This
      review outlines the basic mechanisms of lens regeneration and its induction and
      the possibility of creating lenses by transdifferentiation of the pigment
      epithelial cells, by stem cells or by bioengineering.

PMID- 17005017
TI  - Characterizing regeneration in the vertebrate ear.
AB  - We have previously shown that MRL/MpJ mice have a capacity for regeneration
      instead of scar formation following an ear punch wound. Understanding the
      differences that occur between scar-free regeneration or repair with scarring
      will have great impact upon advances in skin tissue engineering. A key question
      that remains unanswered in the MRL/MpJ mouse model is whether regeneration was
      restricted to the ear or whether it extended to the skin. A histological analysis
      was conducted up to 4 months post-wounding, not only with 2-mm punch wounds to
      the ear but also to the skin on the backs of the same animals. MRL/MpJ mouse ear
      wounds regenerate faster than control strains, with enhanced blastema formation,
      a markedly thickened tip epithelium and reduced scarring. Interestingly, in the
      excisional back wounds, none of these regenerative features was observed and both
      the C57BL/6 control and MRL/MpJ mice healed with scarring. This review gives an
      insight into how this regenerative capacity may be due to evolutionary processes
      as well as ear anatomy. The ear is thin and surrounded on both sides by
      epithelia, and the dorsal skin is devoid of cartilage and under greater tensile
      strain. Analysis of apoptosis during ear regeneration is also discussed,
      assessing the role and expression of various members of the Bcl-2 family of
      proteins. Ongoing studies are focusing on de novo cartilage development in the
      regenerating ear, as well as understanding the role of downstream signalling
      cascades in the process. Identification of such signals could lead to their
      manipulation and use in a novel tissue-engineered skin substitute with scar-free
      integration.

PMID- 17005019
TI  - Cartilage, SOX9 and Notch signals in chondrogenesis.
AB  - Cartilage repair is an ongoing medical challenge. Tissue engineered solutions to
      this problem rely on the availability of appropriately differentiated cells in
      sufficient numbers. This review discusses the potential of primary human
      articular chondrocytes and mesenchymal stem cells to fulfil this role.
      Chondrocytes have been transduced with a retrovirus containing the transcription
      factor SOX9, which permits a greatly improved response of the cells to three
      dimensional culture systems, growth factor stimulation and hypoxic culture
      conditions. Human mesenchymal stem cells have been differentiated into
      chondrocytes using well-established methods, and the Notch signalling pathway has
      been studied in detail to establish its role during this process. Both approaches
      offer insights into these in vitro systems that are invaluable to understanding
      and designing future cartilage regeneration strategies.

PMID- 17005020
TI  - Enhancing tissue integration in cartilage repair procedures.
AB  - Arguably, the gold standard of biological repair of articular cartilage lesions
      is autologous chondrocyte transplantation. Although the clinical outcomes appear
      to range between good and excellent in most cases, there are, nevertheless, both
      clinical and biological challenges that remain to improve rehabilitation and
      clinical outcome. One of the major biological problems relates to tissue
      integration of the reparative tissue into the host tissue at a predictable level.
      Often within a single lesion, varying degrees of integration can be observed from
      total integration through to non-integration as one passes through the defect.
      Here we briefly review some of the literature relating to this problem and
      include some of our own data drawn from questions we have posed about the
      biological nature of cartilage/cartilage integration. The nature and status of
      the tissue that comprises the wound lesion edge is central to tissue integration,
      and controlling aspects of trauma and free-radical-induced cell death together
      with matrix synthesis are identified as two components that require further
      investigation. Interestingly, there appears to be a limited ability of
      chondrocytes to be able to infiltrate existing cartilage matrices and even to
      occupy empty chondrocyte lacunae. Proliferation as a result of blunt and sharp
      trauma shows differential responses. As expected, blunt trauma induces a greater
      proliferative burst than sharp trauma and is more widespread from the lesion
      edge. However, in the case of sharp trauma, the basal cells enter proliferation
      before surface zone chondrocytes, which is not the case in blunt wounds.
      Regulation of these and associated processes will be necessary in order to devise
      strategies that can predict successful integration in biological repair
      procedures.

PMID- 17005018
TI  - Soluble and insoluble signals and the induction of bone formation: molecular
      therapeutics recapitulating development.
AB  - The osteogenic molecular signals of the transforming growth factor-beta (TGF
      beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs) and
      uniquely in primates the TGF-beta isoforms per se, pleiotropic members of the TGF
      beta supergene family, induce de novo endochondral bone formation as a
      recapitulation of embryonic development. Naturally derived BMPs/OPs and gamma
      irradiated human recombinant osteogenic protein-1 (hOP-1) delivered by allogeneic
      and xenogeneic insoluble collagenous matrices initiate de novo bone induction in
      heterotopic and orthotopic sites of the primate Papio ursinus, culminating in
      complete calvarial regeneration by day 90 and maintaining the regenerated
      structures by day 365. The induction of bone by hOP-1 in P. ursinus develops as a
      mosaic structure with distinct spatial and temporal patterns of gene expression
      of members of the TGF-beta superfamily that singly, synergistically and
      synchronously initiate and maintain tissue induction and morphogenesis. The
      temporal and spatial expressions of TGF-beta1 mRNA indicate a specific temporal
      transcriptional window during which expression of TGF-beta1 is mandatory for
      successful and optimal osteogenesis. Highly purified naturally derived bovine
      BMPs/OPs and hOP-1 delivered by human collagenous bone matrices and porous
      hydroxyapatite, respectively, induce bone formation in mandibular defects of
      human patients. By using healthy body sites as bioreactors it is possible to
      recapitulate embryonic developments by inducing selected biomaterials combined
      with recombinant proteins to transform into custom-made prefabricated bone grafts
      for human reconstruction. The osteogenic proteins of the TGF-beta superfamily,
      BMPs/OPs and TGF-betas, the last endowed with the striking prerogative of
      inducing endochondral bone formation in primates only, are helping to engineer
      skeletal reconstruction in molecular terms.

PMID- 17005021
TI  - Cell-matrix biology in vascular tissue engineering.
AB  - We are developing biocompatible small-calibre vascular substitutes based on
      polymeric scaffolds that incorporate cell-matrix signals to enhance vascular cell
      attachment and function. Our graft scaffold comprises an outer electrostatically
      spun porous polyurethane layer seeded with smooth muscle cells, and a luminal
      polycaprolactone layer for endothelial cell attachment. Vascular cell adhesion
      properties of three vascular elastic fibre molecules, tropoelastin, fibrillin-1
      and fibulin-5, have been defined, and adhesion fragments optimized. These
      fragments are being used to coat the scaffolds to enhance luminal endothelial
      cell attachment, and to regulate smooth muscle cell attachment and function.
      Tropoelastin-based cell seeding materials are also being developed. In this way,
      vascular cell-matrix biology is enhancing graft design.

PMID- 17005022
TI  - Biological tooth replacement.
AB  - Teeth develop from a series of reciprocal interactions that take place between
      epithelium and mesenchyme during development of the mouth that begin early in
      mammalian embryogenesis. The molecular control of key processes in tooth
      development such as initiation, morphogenesis and cytodifferentiation are being
      increasingly better understood, to the point where this information can be used
      as the basis for approaches to produce biological replacement teeth (BioTeeth).
      This review outlines the current approaches, ideas and progress towards the
      production of BioTeeth that could form an alternative method for replacing lost
      or damaged teeth.

PMID- 17005024
TI  - Commercial considerations in tissue engineering.
AB  - Tissue engineering is a field with immense promise. Using the example of an early
      tissue-engineered skin implant, Dermagraft, factors involved in the successful
      commercial development of devices of this type are explored. Tissue engineering
      has to strike a balance between tissue culture, which is a resource-intensive
      activity, and business considerations that are concerned with minimizing cost and
      maximizing customer convenience. Bioreactor design takes place in a highly
      regulated environment, so factors to be incorporated into the concept include not
      only tissue culture considerations but also matters related to asepsis, scaleup,
      automation and ease of use by the final customer. Dermagraft is an allogeneic
      tissue. Stasis preservation, in this case cryopreservation, is essential in
      allogeneic tissue engineering, allowing sterility testing, inventory control and,
      in the case of Dermagraft, a cellular stress that may be important for hormesis
      following implantation. Although the use of allogeneic cells provides advantages
      in manufacturing under suitable conditions, it raises the spectre of
      immunological rejection. Such rejection has not been experienced with Dermagraft.
      Possible reasons for this and the vision of further application of allogeneic
      tissues are important considerations in future tissue-engineered cellular
      devices. This review illustrates approaches that indicate some of the criteria
      that may provide a basis for further developments. Marketing is a further
      requirement for success, which entails understanding of the mechanism of action
      of the procedure, and is illustrated for Dermagraft. The success of a tissue
      engineered product is dependent on many interacting operations, some discussed
      here, each of which must be performed simultaneously and well.

PMID- 17005023
TI  - Bioengineered nerve regeneration and muscle reinnervation.
AB  - The peripheral nervous system has the intrinsic capacity to regenerate but the
      reinnervation of muscles is often suboptimal and results in limited recovery of
      function. Injuries to nerves that innervate complex organs such as the larynx are
      particularly difficult to treat. The many functions of the larynx have evolved
      through the intricate neural regulation of highly specialized laryngeal muscles.
      In this review, we examine the responses of nerves and muscles to injury,
      focusing on changes in the expression of neurotrophic factors, and highlight
      differences between the skeletal limb and laryngeal muscle systems. We also
      describe how artificial nerve conduits have become a useful tool for delivery of
      neurotrophic factors as therapeutic agents to promote peripheral nerve repair and
      might eventually be useful in the treatment of laryngeal nerve injury.

PMID- 17005025
TI  - Microscopic and histological examination of the mouse hindpaw digit and flexor
      tendon arrangement with 3D reconstruction.
AB  - Mice are currently the species of choice for the in vivo study of injury, but few
      detailed anatomical descriptions have been made of rodent digits, limiting their
      use for the investigation of intrasynovial tendon healing. In this study a
      detailed microscopic and histological investigation was performed using C57/BL6
      and Tie2 LacZ reporter gene transgenic mice. Serial-sectioned mouse hindpaw
      digits were characterized using haematoxylin and eosin, Masson's trichrome
      (collagen), Alcian blue (fibrocartilage), Miller's stain (elastin) and TRITC
      phalloidin (cellular cytoskeleton) staining. Digital vasculature was demonstrated
      using FITC-labelled dextran perfusion studies supplemented with LacZ expression
      in Tie2 LacZ transgenic mice digits. Imaging of the digit used a combination of
      brightfield and confocal microscopy with three-dimensional reconstruction. Our
      findings demonstrated that the mouse hindpaw possesses deep and superficial
      flexor tendons within a synovial sheath comparable with that found in other
      mammalian species. The intrasynovial tendons were avascular and had regions of
      fibrocartilaginous specialization relating to areas of compression. Corresponding
      vascular networks were demonstrated around the sheath using Tie2 LacZ mice and
      FITC-perfused hindpaws. Furthermore, there is an area of digit where both deep
      and superficial tendons reside between two pulleys, similar to zone 2 in the
      human hand where it would be possible to study intrasynovial tendon injury and
      adhesion formation. In conclusion, although the dimensions of the mouse digit
      pose technical challenges for surgical intervention, we have identified a model
      for the study of flexor tendon injury that will permit future genetic
      manipulation studies.

PMID- 17005026
TI  - Location of injury influences the mechanisms of both regeneration and repair
      within the MRL/MpJ mouse.
AB  - The adult MRL/MpJ mouse regenerates all differentiated structures after through
      and-through ear punch wounding in a scar-free process. We investigated whether
      this regenerative capacity was also shown by skin wounds. Dorsal skin wounds were
      created, harvested and archived from the same animals (MRL/MpJ and C57BL/6 mice)
      that received through-and-through ear punch wounds. Re-epithelialization was
      complete in dorsal wounds in both strains by day 5 and extensive granulation
      tissue was present by day 14 post-wounding. By day 21, wounds from both strains
      contained dense amounts of collagen that healed with a scar. The average wound
      area, as well as alpha-smooth muscle actin expression and macrophage influx were
      investigated during dorsal skin wound healing and did not significantly differ
      between strains. Thus, MRL/MpJ mice regenerate ear wounds in a scar-free manner,
      but heal dorsal skin wounds by simple repair with scar formation. A significant
      conclusion can be drawn from these data; mechanisms of regeneration and repair
      can occur within the same animal, potentially utilizing similar molecules and
      signalling pathways that subtly diverge dependent upon the microenvironment of
      the injury.

PMID- 17005028
TI  - Colchicine in acute gouty arthritis: the optimum dose?

PMID- 17005031
TI  - 18th international symposium on Intensive Care and Emergency Medicine. Brussels,
      Belgium. 17-20 March 1998. Abstracts.

PMID- 17005036
TI  - Construction of doxycyline-dependent mini-HIV-1 variants for the development of a
      virotherapy against leukemias.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is a high-risk type of blood-cell
      cancer. We describe the improvement of a candidate therapeutic virus for
      virotherapy of leukemic cells. Virotherapy is based on the exclusive replication
      of a virus in leukemic cells, leading to the selective removal of these malignant
      cells. To improve the safety of such a virus, we constructed an HIV-1 variant
      that replicates exclusively in the presence of the nontoxic effector doxycycline
      (dox). This was achieved by replacement of the viral TAR-Tat system for
      transcriptional activation by the Escherichia coli-derived Tet system for
      inducible gene expression. This HIV-rtTA virus replicates in a strictly dox
      dependent manner. In this virus, additional deletions and/or inactivating
      mutations were introduced in the genes for accessory proteins. These proteins are
      essential for virus replication in untransformed cells, but dispensable in
      leukemic T cells. These minimized HIV-rtTA variants contain up to 7
      deletions/inactivating mutations (TAR, Tat, vif, vpR, vpU, nef and U3) and
      replicate efficiently in the leukemic SupT1 T cell line, but do not replicate in
      normal peripheral blood mononuclear cells. These virus variants are also able to
      efficiently remove leukemic cells from a mixed culture with untransformed cells.
      The therapeutic viruses use CD4 and CXCR4 for cell entry and could potentially be
      used against CXCR4 expressing malignancies such as T-lymphoblastic
      leukemia/lymphoma, NK leukemia and some myeloid leukemias.

PMID- 17005037
TI  - How a well-grounded minimal important difference can enhance transparency of
      labelling claims and improve interpretation of a patient reported outcome
      measure.
AB  - The evaluation and use of patient reported outcome (PRO) measures requires
      detailed understanding of the meaning of the outcome of interest. The Food and
      Drug Administration (FDA) recently presented its draft guidance and view on the
      use of PRO measures as endpoints in clinical trials. One section of the guidance
      document specifically deals with advice about the use of the minimal important
      difference (MID) that we redefined as the smallest difference in score in the
      outcome of interest that informed patients or informed proxies perceive as
      important. The advice, however, is short, indeed much too short. We believe that
      expanding the section and making it more specific will benefit all stakeholders:
      patients, clinicians, other clinical decision makers, those designing trials and
      making claims, payers and the FDA. There is no "gold standard" methodology of
      estimating the MID or achieving the meaningfulness of clinical trial results
      based on patient reported outcomes. There are many methods of estimating the MID
      usually grouped into two distinct categories: anchor-based methods, that examine
      the relationship between scores on the target instrument and some independent
      measure, and distribution-based methods resorting to the statistical
      characteristics of the obtained scores. Estimation of an MID and interpretation
      of clinical trial results that present patient important outcomes is demanding
      but vital for informing the decision to recommend approve a given intervention.
      Investigators are encouraged to use reliable and valid methods to achieve
      meaningfulness of their results, preferably those that rely on patients to
      estimate what constitutes a minimal important, small, moderate, or large
      difference. However, acquiring the meaningfulness of PRO measures transcends
      beyond a concept of the MID and we advocate that dichotomizing the scores of
      patient-reported outcome measures facilitate interpretability of clinical trial
      results for those who need to understand trial results after a labelling claim
      has been granted. Irrespective of the strategy investigators use to estimate
      these values, from the individual patient perspective it is much more relevant if
      investigators report both the estimated thresholds and the proportion of patients
      achieving that benefit.

PMID- 17005038
TI  - Responsiveness and minimal important differences for patient reported outcomes.
AB  - Patient reported outcomes provide the patient's perspective on the effectiveness
      of treatment. The draft Food and Drug Administration guidance on patient reported
      outcomes for labeling and promotional claims raises a number of method and
      measurement issues that require further clarification, including methods of
      determining responsiveness and minimal important differences. For clinical
      trials, instruments need to be based on a clear conceptual framework, have
      evidence supporting content validity and acceptable psychometric qualities. The
      measures must also have evidence documenting responsiveness and interpretation
      guidelines (i.e., minimal important difference) to be most useful as
      effectiveness endpoints in clinical trials. The recommended approach is to
      estimate the minimal important difference based on several anchor-based methods,
      with relevant clinical or patient-based indicators, and to examine various
      distribution-based estimates (i.e., effect size, standardized response mean,
      standard error of measurement) as supportive information, and then to triangulate
      on a single value or small range of values for the MID. Confidence in a specific
      MID value evolves over time and is confirmed by additional research evidence,
      including clinical trial experience. The MID may vary by population and context,
      and no one MID will be valid for all study applications involving a PRO
      instrument. Responsiveness and MID must be demonstrated and documented for the
      particular study population, and these measurement characteristics are needed for
      PRO labeling and promotional claims.

PMID- 17005039
TI  - The Mectizan Donation Program - highlights from 2005.
AB  - Through the Mectizan Donation Program, Merck & Co., Inc. has donated Mectizan
      (ivermectin, MSD) for the treatment of onchocerciasis worldwide since 1987.
      Mectizan has also been donated for the elimination of lymphatic filariasis (LF)
      since 1998 in African countries and in Yemen where onchocerciasis and LF are co
      endemic; for LF elimination programs, Mectizan is co-administered with
      albendazole, which is donated by GlaxoSmithKline. The Mectizan Donation Program
      works in collaboration with the Mectizan Expert Committee/Albendazole
      Coordination, its scientific advisory committee. In 2005, a total of 62,201,310
      treatments of Mectizan for onchocerciasis were approved for delivery via mass
      treatment programs in Africa, Latin America, and Yemen. Seventy-seven percent and
      20% of these treatments for onchocerciasis were for countries included in the
      African Programme for Onchocerciasis Control (APOC) and the former-Onchocerciasis
      Control Programme in West Africa (OCP), respectively. The remaining 3% of
      treatments approved were for the six onchocerciasis endemic countries in Latin
      America, where mass treatment is carried out twice-yearly with the goal of
      completely eliminating morbidity and eventually transmission of infection, and
      for Yemen. All 33 onchocerciasis endemic countries where mass treatment with
      Mectizan is indicated have ongoing mass treatment programs. In 2005, 42,052,583
      treatments of co-administered albendazole and Mectizan were approved for national
      Programs to Eliminate LF (PELFs) in Africa and Yemen. There are ongoing PELFs
      using albendazole and Mectizan in nine African countries and Yemen; these
      represent 35% of the total number of countries expected to require the co
      administration of these two chemotherapeutic agents for LF elimination. In
      Africa, the expansion of existing PELFs and the initiation of new ones have been
      hampered by lack of resources, technical difficulties with the mapping of LF
      endemicity, and the co-endemicity of LF and loiasis. Included in this review are
      recommendations recently put forward for the co-administration of albendazole and
      Mectizan in areas endemic for LF, loiasis, and onchocerciasis.

PMID- 17005040
TI  - Relationship between nocturnal serotonin surge and melatonin onset in rodent
      pineal gland.
AB  - BACKGROUND: We have recently reported dynamic circadian rhythms of serotonin (5
      HT, 5-hydroxytryptamine) output in the pineal gland of rat, which precedes the
      onset of N-acetylserotonin (NAS) and melatonin secretion at night. The present
      study was aimed at investigating in detail the relationship between 5-HT onset
      (5HT-on) and melatonin onset (MT-on) in multiple strains of rats and comparing
      them with those of hamsters. METHODS: Animals were maintained in chambers
      equipped with light (250 lux at cage levels) and ventilation in a temperature
      controlled room. Following surgical implantation of a microdialysis probe in the
      pineal gland, animals were individually housed for on-line pineal microdialysis
      and for automated HPLC analysis of 5-HT and melatonin. Animals were under a light
      dark cycle of 12:12 h for the duration of the experiments. RESULTS: All animals
      displayed dynamic 5-HT and melatonin rhythms at night. In all cases, 5HT-on
      (taken at 80% of the daily maximum levels) preceded MT-on (taken at 20% of the
      daily maximum levels). Within the same animals, 5HT-on as well as MT-on across
      multiple circadian cycles exhibited minimum variations under entrained
      conditions. Large inter-individual variations of both 5HT-on and MT-on were found
      in outbred rats and hamsters under entrained conditions. In comparison, inbred
      rats displayed very small individual variations of 5HT-on and MT-on. Importantly,
      we have uncovered a species-specific relationship of 5HT-on and MT-on. 5HT-on of
      rats, regardless of the strain, preceded MT-on of the same rats by 50 min. In
      contrast, 5HT-on of hamsters led MT-on by as much as 240 min. Thus, while a
      constant relationship of 5HT-on and MT-on exists for animals of the same species,
      the relative timings of 5HT-on and MT-on differ between animals of different
      species. CONCLUSION: These results suggest that both 5-HT and melatonin could
      serve as reliable markers of the circadian clock because of their day-to-day
      precision of onset timings within the same animals or within individuals of the
      same strain or same species. The results also demonstrate that data for MT-on
      cannot be compared directly between different species, and that 5HT-on may be a
      more reliable circadian marker when data from animals of different species are
      compared.

PMID- 17005041
TI  - Individual freedoms versus collective responsibility: immunization decision
      making in the face of occasionally competing values.
AB  - Modern public health strives for maximizing benefits for the highest number of
      people while protecting individual rights. Restrictions on individual rights are
      justified for two reasons--for the benefit of the individual or the benefit of
      the community. In extreme situations there may be a need to protect the health of
      an individual and particularly a child; even by overriding individual/parental
      autonomy. However, The American Academy of Pediatrics recently concluded that
      "Continued (vaccine) refusal after adequate discussion should be respected unless
      the child is put at significant risk of serious harm (as, for example, might be
      the case during an epidemic). Only then should state agencies be involved to
      override parental discretion on the basis of medical neglect". Many countries
      have compulsory immunization requirements. These laws curtail individual autonomy
      in order to protect the community from infectious diseases because unvaccinated
      individuals pose risk to the community--including vaccinated individuals (since
      vaccines are not 100% efficacious), children too young to be vaccinated, and
      persons who have medical vaccine contraindications. There are situations where
      there can be a real or perceived divergence between individual and community
      benefits of vaccination. This divergence may occasionally be based upon current
      scientific evidence and may exemplify the need for overriding individual
      autonomy. A divergence between individual and community benefits may also exist
      when there are ideological beliefs incongruent with vaccination or individuals
      are unaware of or do not accept available scientific evidence. When the state
      curtails individual freedoms for the collective good, it should address several
      issues including the magnitude of the individual and community risk, the strength
      of the individual's conviction, wider and long-term consequences of restricting
      individual autonomy, effective risk communication, best available scientific
      evidence, and transparency of the decision making process.

PMID- 17005042
TI  - Evaluation of a new self-contained, ambulatory, objective cough monitor.
AB  - OBJECTIVE AND BACKGROUND: Objective monitoring of cough may be preferred to
      subjective reporting of the symptom in clinical and research settings. Therefore,
      a self-contained, ambulatory cough monitoring system is needed that is non
      invasive, usable for children and adults of all ages, inexpensive, and highly
      accurate with easy to use analysis software. METHODOLOGY: After development of a
      new device, 15 subjects with frequent coughing were recorded with the novel cough
      monitor and a simultaneous video recording in order to validate the monitor
      compared with a gold standard. Two investigators independently analyzed the
      recordings and counted the number of coughs during the study period from both the
      cough monitor and the video recording. RESULTS: When measuring agreement between
      the two investigators, the sample concordance correlation coefficient for audio
      counts was 0.998 (p < 0.001). In the comparison of video counts, the sample
      concordance correlation coefficient was 0.997 (p < 0.001). For the comparison of
      investigator 1's video counts to the corresponding audio counts, the sample
      concordance correlation coefficient was 0.968 (p = 0.026). For the comparison of
      investigator 2's video counts to the corresponding counts, the sample concordance
      correlation coefficient was 0.973 (p = 0.015). CONCLUSION: We have developed and
      piloted a new, valid, and reproducible method of objectively recording and
      analyzing cough. This device appears to be useful for subjects of any age and in
      clinical and research settings.

PMID- 17005043
TI  - The validity and responsiveness of three quality of life measures in the
      assessment of psoriasis patients: results of a phase II study.
AB  - BACKGROUND: Patient-reported outcome (PROs) measures are being used more
      frequently in investigational studies of treatments for moderate to severe plaque
      psoriasis. The objective of this study was to examine the relationships among the
      Dermatology Life Quality Index (DLQI), the Short Form 36 (SF-36), and the EuroQOL
      5D (EQ-5D) and to assess their validity, responsiveness, and estimates of minimum
      important differences. METHODS: A Phase II, randomized, double-blind, parallel
      group, placebo-controlled, multi-center clinical trial assessed the clinical
      efficacy and safety of two doses of subcutaneously administered adalimumab vs.
      placebo for 12 weeks in the treatment of 147 patients with moderate to severe
      plaque psoriasis. This study provided the opportunity to evaluate the validity
      and responsiveness to change in clinical status of PROs instruments. Patients
      completed the DLQI, SF-36, and EQ-5D questionnaires at baseline and at 12 weeks.
      Blinded investigators assessed the Psoriasis Area and Severity Index (PASI)
      scores and the Physician's Global Assessment (PGA) scores of enrolled patients.
      The responsiveness of the measures to changes in the clinical endpoints from
      baseline to Week 12 was assessed. Estimates of minimum important differences
      (MID) were derived. All analyses were performed with blinded data; findings and
      conclusions were not biased based on treatment condition. RESULTS: The
      dermatology-specific DLQI was highly correlated to clinical endpoints at baseline
      and at Week 12, and was the most responsive PRO to changes in endpoints. Compared
      with the SF-36, the EQ-5D index score and VAS scores were generally more highly
      correlated with clinical endpoints, but displayed about the same degree of
      responsiveness. The most responsive SF-36 scales were the Bodily Pain and Social
      Functioning scales. Estimates of the MID for the DLQI ranged from 2.3-5.7 and for
      the SF-36 Physical Component Summary (PCS) score ranged from 2.5-3.9. CONCLUSION:
      This study provides support for the continued use of the DLQI and SF-36 PCS in
      the assessment of treatments for psoriasis. On the basis of the results from this
      trial, the EQ-5D should be considered as a general PRO measure in future clinical
      trials of patients with moderate to severe plaque psoriasis.

PMID- 17005045
TI  - Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in
      medical inpatients.
AB  - BACKGROUND: Clinical trials have shown low-molecular weight heparin (LMWH) to be
      at least as safe and efficacious as unfractionated heparin (UFH) for preventing
      venous thromboembolism (VTE) in acutely-ill medical inpatients. OBJECTIVE: To
      compare clinical and economic outcomes among acutely-ill medical inpatients
      receiving the LMWH enoxaparin versus UFH prophylaxis in clinical practice.
      METHODS: Using a large, multi-hospital, US database, we identified persons aged >
      or =40 years hospitalized for > or =6 days for an acute medical condition
      (including circulatory disorders, respiratory disorders, infectious diseases, or
      neoplasms) from Q4 1999 to Q1 2002. From these patients, those who received
      thromboprophylaxis with either enoxaparin or UFH were identified. Surgical
      patients and those requiring or ineligible for anticoagulation were excluded. We
      compared the incidence of deep-vein thrombosis (DVT), pulmonary embolism (PE),
      and all VTE (i.e., DVT and/or PE). Secondary outcomes were occurrence of side
      effects, length of hospital stay and total costs. RESULTS: 479 patients received
      enoxaparin prophylaxis and 2,837 received UFH. The incidence of VTE was 1.7% with
      enoxaparin prophylaxis versus 6.3% with UFH (RR = 0.26; p < 0.001). Occurrence of
      side effects, length of stay (10.00 days with enoxaparin vs. 10.26 days with UFH;
      p = 0.348) and total costs ($18,777 vs. $17,602; p = 0.463) were similar in the 2
      groups. CONCLUSION: We observed a 74% lower risk of VTE among patients receiving
      enoxaparin prophylaxis versus UFH prophylaxis. There was no significant
      difference in side effects or economic outcomes. These results provide evidence
      that the LMWH enoxaparin is more effective than UFH in reducing the risk of VTE
      in current clinical practice.

PMID- 17005044
TI  - Altered intercellular communication in lung fibroblast cultures from patients
      with idiopathic pulmonary fibrosis.
AB  - RATIONALE: Gap junctions are membrane channels formed by an array of connexins
      which links adjacent cells realizing an electro- metabolic synapse. Connexin
      mediated communication is crucial in the regulation of cell growth,
      differentiation, and development. The activation and proliferation of
      phenotypically altered fibroblasts are central events in the pathogenesis of
      idiopathic pulmonary fibrosis. We sought to evaluate the role of connexin-43, the
      most abundant gap-junction subunit in the human lung, in the pathogenesis of this
      condition. METHODS: We investigated the transcription and protein expression of
      connexin-43 and the gap-junctional intercellular communication (GJIC) in 5
      primary lung fibroblast lines derived from normal subjects (NF) and from 3
      histologically proven IPF patients (FF). RESULTS: Here we show that connexin-43
      mRNA was significantly reduced in FF as demonstrated by standard and quantitative
      RT-PCR. GJIC was functionally evaluated by means of flow-cytometry. In order to
      demonstrate that dye spreading was taking place through gap junctions, we used
      carbenoxolone as a pharmacological gap-junction blocker. Carbenoxolone
      specifically blocked GJIC in our system in a concentration dependent manner. FF
      showed a significantly reduced homologous GJIC compared to NF. Similarly, GJIC
      was significantly impaired in FF when a heterologous NF line was used as dye
      donor, suggesting a complete defect in GJIC of FF. CONCLUSION: These results
      suggest a novel alteration in primary lung fibroblasts from IPF patients. The
      reduced Cx43 expression and the associated alteration in cell-to-cell
      communication may justify some of the known pathological characteristic of this
      devastating disease that still represents a challenge to the medical practice.

PMID- 17005046
TI  - Reduction of inequalities in health: assessing evidence-based tools.
AB  - BACKGROUND: The reduction of health inequalities is a focus of many national and
      international health organisations. The need for pragmatic evidence-based
      approaches has led to the development of a number of evidence-based equity
      initiatives. This paper describes a new program that focuses upon evidence- based
      tools, which are useful for policy initiatives that reduce inequities. METHODS:
      This paper is based on a presentation that was given at the "Regional
      Consultation on Policy Tools: Equity in Population Health Reports," held in
      Toronto, Canada in June 2002. RESULTS: Five assessment tools were presented. 1. A
      database of systematic reviews on the effects of educational, legal, social, and
      health interventions to reduce unfair inequalities is being established through
      the Cochrane and Campbell Collaborations. 2 Decision aids and shared decision
      making can be facilitated in disadvantaged groups by 'health coaches' to help
      people become better decision makers, negotiators, and navigators of the health
      system; a pilot study in Chile has provided proof of this concept. 3. The CIET
      Cycle: Combining adapted cluster survey techniques with qualitative methods,
      CIET's population based applications support evidence-based decision making at
      local and national levels. The CIET map generates maps directly from survey or
      routine institutional data, to be used as evidence-based decisions aids. Complex
      data can be displayed attractively, providing an important tool for studying and
      comparing health indicators among and between different populations. 4. The
      Ottawa Equity Gauge is applying the Global Equity Gauge Alliance framework to an
      industrialised country setting. 5 The Needs-Based Health Assessment Toolkit,
      established to assemble information on which clinical and health policy decisions
      can be based, is being expanded to ensure a focus on distribution and average
      health indicators. CONCLUSION: Evidence-based planning tools have much to offer
      the goal of equitable health development.

PMID- 17005047
TI  - Multiple effects govern endogenous retrovirus survival patterns in human gene
      introns.
AB  - BACKGROUND: Endogenous retroviruses (ERVs) and solitary long terminal repeats
      (LTRs) have a significant antisense bias when located in gene introns, suggesting
      strong negative selective pressure on such elements oriented in the same
      transcriptional direction as the enclosing gene. It has been assumed that this
      bias reflects the presence of strong transcriptional regulatory signals within
      LTRs but little work has been done to investigate this phenomenon further.
      RESULTS: In the analysis reported here, we found significant differences between
      individual human ERV families in their prevalence within genes and degree of
      antisense bias and show that, regardless of orientation, ERVs of most families
      are less likely to be found in introns than in intergenic regions. Examination of
      density profiles of ERVs across transcriptional units and the transcription
      signals present in the consensus ERVs suggests the importance of splice acceptor
      sites, in conjunction with splice donor and polyadenylation signals, as the major
      targets for selection against most families of ERVs/LTRs. Furthermore, analysis
      of annotated human mRNA splicing events involving ERV sequence revealed that the
      relatively young human ERVs (HERVs), HERV9 and HERV-K (HML-2), are involved in no
      human mRNA splicing events at all when oriented antisense to gene transcription,
      while elements in the sense direction in transcribed regions show considerable
      bias for use of strong splice sites. CONCLUSION: Our observations suggest
      suppression of splicing among young intronic ERVs oriented antisense to gene
      transcription, which may account for their reduced mutagenicity and higher
      fixation rate in gene introns.

PMID- 17005048
TI  - Comparative assessment of performance and genome dependence among phylogenetic
      profiling methods.
AB  - BACKGROUND: The rapidly increasing speed with which genome sequence data can be
      generated will be accompanied by an exponential increase in the number of
      sequenced eukaryotes. With the increasing number of sequenced eukaryotic genomes
      comes a need for bioinformatic techniques to aid in functional annotation.
      Ideally, genome context based techniques such as proximity, fusion, and
      phylogenetic profiling, which have been so successful in prokaryotes, could be
      utilized in eukaryotes. Here we explore the application of phylogenetic
      profiling, a method that exploits the evolutionary co-occurrence of genes in the
      assignment of functional linkages, to eukaryotic genomes. RESULTS: In order to
      evaluate the performance of phylogenetic profiling in eukaryotes, we assessed the
      relative performance of commonly used profile construction techniques and genome
      compositions in predicting functional linkages in both prokaryotic and eukaryotic
      organisms. When predicting linkages in E. coli with a prokaryotic profile, the
      use of continuous values constructed from transformed BLAST bit-scores performed
      better than profiles composed of discretized E-values; the use of discretized E
      values resulted in more accurate linkages when using S. cerevisiae as the query
      organism. Extending this analysis by incorporating several eukaryotic genomes in
      profiles containing a majority of prokaryotes resulted in similar overall
      accuracy, but with a surprising reduction in pathway diversity among the most
      significant linkages. Furthermore, the application of phylogenetic profiling
      using profiles composed of only eukaryotes resulted in the loss of the strong
      correlation between common KEGG pathway membership and profile similarity score.
      Profile construction methods, orthology definitions, ontology and domain
      complexity were explored as possible sources of the poor performance of
      eukaryotic profiles, but with no improvement in results. CONCLUSION: Given the
      current set of completely sequenced eukaryotic organisms, phylogenetic profiling
      using profiles generated from any of the commonly used techniques was found to
      yield extremely poor results. These findings imply genome-specific requirements
      for constructing functionally relevant phylogenetic profiles, and suggest that
      differences in the evolutionary history between different kingdoms might
      generally limit the usefulness of phylogenetic profiling in eukaryotes.

PMID- 17005049
TI  - The POETICs of industrial carbon dioxide emissions in Japan: an urban and
      institutional extension of the IPAT identity.
AB  - BACKGROUND: This study applies the POETICs framework (population, organization,
      environment, technology, institutions and culture) to an analysis of industrial
      carbon dioxide emissions in Japanese cities. The inclusion of institutional
      variables in the form of International Council for Local Environmental
      Initiatives membership, ISO 14001 implementation, and non-profit sector activity
      addresses the ecological limitations of the often used IPAT (impact = population
      x affluence x technology) approach. RESULTS: Results suggest the weak existence
      of an environmental Kuznets curve, in which the wealthiest cities are reducing
      their emissions through increased efficiency. Significant institutional impacts
      are also found to hold in the predicted directions. Specifically, panel and cross
      sectional regressions indicate that membership in the International Council for
      Local Environmental Initiatives and non-profit organizational presence have
      negative effects on industrial carbon dioxide emissions. CONCLUSION: The presence
      of institutional drivers at the city level provides empirical support for the
      POETICs rubric, which recasts the ecological framing of the IPAT identity in a
      more sociological mold. The results also indicate that Japanese civil society has
      a role to play in carbon mitigation. More refined studies need to take into
      consideration an expanded set of methods, drivers, and carbon budgets, as applied
      to a broader range of cases outside of Japan, to more accurately assess how civil
      society can bridge the issue of scale that separates local level policy concerns
      from global level climate dynamics.

PMID- 17005050
TI  - Implementation of case management to reduce cardiovascular disease risk in the
      Stanford and San Mateo Heart to Heart randomized controlled trial: study protocol
      and baseline characteristics.
AB  - BACKGROUND: Case management has emerged as a promising alternative approach to
      supplement traditional one-on-one sessions between patients and doctors for
      improving the quality of care in chronic diseases such as coronary heart disease
      (CHD). However, data are lacking in terms of its efficacy and cost-effectiveness
      when implemented in ethnic and low-income populations. METHODS: The Stanford and
      San Mateo Heart to Heart (HTH) project is a randomized controlled clinical trial
      designed to rigorously evaluate the efficacy and cost-effectiveness of a multi
      risk cardiovascular case management program in low-income, primarily ethnic
      minority patients served by a local county health care system in California.
      Randomization occurred at the patient level. The primary outcome measure is the
      absolute CHD risk over 10 years. Secondary outcome measures include adherence to
      guidelines on CHD prevention practice. We documented the study design,
      methodology, and baseline sociodemographic, clinical and lifestyle
      characteristics of 419 participants. RESULTS: We achieved equal distributions of
      the sociodemographic, biophysical and lifestyle characteristics between the two
      randomization groups. HTH participants had a mean age of 56 years, 63% were
      Latinos/Hispanics, 65% female, 61% less educated, and 62% were not employed.
      Twenty percent of participants reported having a prior cardiovascular event. 10
      year CHD risk averaged 18% in men and 13% in women despite a modest low-density
      lipoprotein cholesterol level and a high on-treatment percentage at baseline.
      Sixty-three percent of participants were diagnosed with diabetes and an
      additional 22% had metabolic syndrome. In addition, many participants had
      depressed high-density lipoprotein (HDL) cholesterol levels and elevated values
      of total cholesterol-to-HDL ratio, triglycerides, triglyceride-to-HDL ratio, and
      blood pressure. Furthermore, nearly 70% of participants were obese, 45% had a
      family history of CHD or stroke, and 16% were current smokers. CONCLUSION: We
      have recruited an ethnically diverse, low-income cohort in which to implement a
      case management approach and test its efficacy and cost-effectiveness. HTH will
      advance the scientific understanding of better strategies for CHD prevention
      among these priority subpopulations and aid in guiding future practice that will
      reduce health disparities.

PMID- 17005051
TI  - The impact of a decision aid about heart disease prevention on patients'
      discussions with their doctor and their plans for prevention: a pilot randomized
      trial.
AB  - BACKGROUND: Low utilization of effective coronary heart disease (CHD) prevention
      strategies may be due to many factors, but chief among them is the lack of
      patient involvement in prevention decisions. We undertook this study to test the
      effectiveness of an individually-tailored, computerized decision aid about CHD on
      patients' discussions with their doctor and their plans for CHD prevention.
      METHODS: We conducted a pilot randomized trial in a convenience sample of adults
      with no previous history of cardiovascular disease to test the effectiveness of
      an individually-tailored, computerized decision aid about CHD prevention against
      a risk factor list that patients could present to their doctor. RESULTS: We
      enrolled 75 adults. Mean age was 53. 59% were female, 73% white, and 23% African
      American. 66% had some college education. 43% had a 10-year CHD risk of 0-5%, 25%
      a risk of 6-10%, 24% a risk of 11-20%, and 5% a risk of > 20%. 78% had at least
      one option to reduce their CHD risk, but only 45% accurately identified the
      strategies best supported by evidence. 41 patients received the decision aid, 34
      received usual care. In unadjusted analysis, the decision aid increased the
      proportion of patients who discussed CHD risk reduction with their doctor from
      24% to 40% (absolute difference 16%; 95% CI -4% to +37%) and increased the
      proportion who had a specific plan to reduce their risk from 24% to 37% (absolute
      difference 13%; 95% CI -7% to +34%). In pre-post testing, the decision aid also
      appeared to increase the proportion of patients with plans to intervene on their
      CHD risk (absolute increase ranging from 21% to 47% for planned medication use
      and 5% to 16% for planned behavioral interventions). CONCLUSION: Our study
      confirms patients' limited knowledge about their CHD risk and effective risk
      reduction options and provides preliminary evidence that an individually-tailored
      decision aid about CHD prevention might be expected to increase patients'
      discussions about CHD prevention with their doctor and their plans for CHD risk
      reduction. These findings should be replicated in studies with a larger sample
      size and patients at overall higher risk of CHD.

PMID- 17005052
TI  - Expression profiles for macrophage alternative activation genes in AD and in
      mouse models of AD.
AB  - BACKGROUND: Microglia are associated with neuritic plaques in Alzheimer disease
      (AD) and serve as a primary component of the innate immune response in the brain.
      Neuritic plaques are fibrous deposits composed of the amyloid beta-peptide
      fragments (Abeta) of the amyloid precursor protein (APP). Numerous studies have
      shown that the immune cells in the vicinity of amyloid deposits in AD express
      mRNA and proteins for pro-inflammatory cytokines, leading to the hypothesis that
      microglia demonstrate classical (Th-1) immune activation in AD. Nonetheless, the
      complex role of microglial activation has yet to be fully explored since recent
      studies show that peripheral macrophages enter an "alternative" activation state.
      METHODS: To study alternative activation of microglia, we used quantitative RT
      PCR to identify genes associated with alternative activation in microglia,
      including arginase I (AGI), mannose receptor (MRC1), found in inflammatory zone 1
      (FIZZ1), and chitinase 3-like 3 (YM1). RESULTS: Our findings confirmed that
      treatment of microglia with anti-inflammatory cytokines such as IL-4 and IL-13
      induces a gene profile typical of alternative activation similar to that
      previously observed in peripheral macrophages. We then used this gene expression
      profile to examine two mouse models of AD, the APPsw (Tg-2576) and Tg-SwDI,
      models for amyloid deposition and for cerebral amyloid angiopathy (CAA)
      respectively. AGI, MRC1 and YM1 mRNA levels were significantly increased in the
      Tg-2576 mouse brains compared to age-matched controls while TNFalpha and NOS2
      mRNA levels, genes commonly associated with classical activation, increased or
      did not change, respectively. Only TNFalpha mRNA increased in the Tg-SwDI mouse
      brain. Alternative activation genes were also identified in brain samples from
      individuals with AD and were compared to age-matched control individuals. In AD
      brain, mRNAs for TNFalpha, AGI, MRC1 and the chitinase-3 like 1 and 2 genes
      (CHI3L1; CHI3L2) were significantly increased while NOS2 and IL-1beta mRNAs were
      unchanged. CONCLUSION: Immune cells within the brain display gene profiles that
      suggest heterogeneous, functional phenotypes that range from a pro-inflammatory,
      classical activation state to an alternative activation state involved in repair
      and extracellular matrix remodeling. Our data suggest that innate immune cells in
      AD may exhibit a hybrid activation state that includes characteristics of
      classical and alternative activation.

PMID- 17005053
TI  - Preparation of platelet-rich plasma as a tissue adhesive for experimental
      transplantation in rabbits.
AB  - PURPOSE: Platelet-rich plasma (PRP) is an autologous substance with adhesive
      properties. We aimed at developing and testing the efficacy of a method for PRP
      preparation in rabbits. MATERIALS AND METHODS: An in vitro study was carried out
      to obtain PRP from forty rabbits and to analyze the number of platelets and type
      of substance needed to trigger platelet activation. To induce platelet
      activation, 5%, 10%, 25% and 50% CaCl solutions were used. Then, an in vivo study
      was performed in twelve rabbits to test PRP adhesiveness in lamellar corneal
      graft. A control group made up of six rabbits underwent corneal transplantation
      without using PRP. RESULTS: 5% CaCl was the most effective concentration in
      activating PRP, with a mean time of 19 minutes. An attached corneal flap was seen
      3 months after surgery. A detached corneal button was seen in all controls.
      CONCLUSION: Our method was able to produce rabbit-derived PRP with suitable
      properties for soft tissue adhesion. These results could be useful for
      researchers of the growing fields of tissue repair and experimental
      transplantation.

PMID- 17005054
TI  - Respiratory symptoms: a reason to obtain spirometry.

PMID- 17005055
TI  - Continuous exhaled breath condensate measurements in ventilated patients: "I
      don't know what you guys are measuring, but you're certainly measuring it!".

PMID- 17005056
TI  - Discrepancy in the use of confirmatory tests in patients hospitalized with the
      diagnosis of chronic obstructive pulmonary disease or congestive heart failure.
AB  - OBJECTIVE: To determine the prevalence of confirmatory use of spirometry in
      patients admitted to a tertiary-care facility with the diagnosis of chronic
      obstructive pulmonary disease (COPD), including those with respiratory failure,
      and compare that to the use of confirmatory 2-dimensional echocardiography (2-D
      echo) in patients admitted with the diagnosis of congestive heart failure (CHF),
      to determine preferential confirmatory testing practices. SETTING: Academic
      tertiary-care hospital. METHODS: A 6-month retrospective review of charts of
      patients with a primary or secondary discharge diagnosis of COPD, respiratory
      failure, and CHF, using the appropriate International Classification of Diseases,
      Ninth Revision, Clinical Modification codes. Pulmonary function and
      echocardiography laboratory databases were reviewed to determine if the patients
      had had spirometry or 2-D echo performed during the 8 years prior to the study
      period. RESULTS: Five hundred fifty-three patients were discharged with the
      diagnosis of COPD, and 173 patients (31%) had had spirometry. In contrast, 789
      patients had the diagnosis of CHF, and a larger proportion of them (619 patients,
      78%) had had 2-D echo (p < 0.001). Only 35% of the patients with respiratory
      failure and COPD had spirometry performed. There were a total of 219 patients
      with concomitant diagnoses of COPD and CHF. A majority of them (48%) had a 2-D
      echo as the only confirmatory test, 74 (34%) had both tests performed, 4 (2%) had
      spirometry only, and 36 (16%) had neither test performed. Of the patients with a
      diagnosis of COPD who had spirometry, 30% had spirometry findings consistent with
      restrictive or normal physiology. CONCLUSIONS: A large proportion of patients
      hospitalized with the diagnosis of COPD have never had a confirmatory test,
      including those with presumably advanced disease. Compared to patients with CHF,
      patients with COPD are less likely to have had the confirmatory test performed,
      even when both conditions coexist. Many patients with the clinical diagnosis of
      COPD have an inconsistent physiologic diagnosis. To impact the increasingly
      important problem of COPD, we must raise awareness of the need to confirm its
      diagnosis and severity with spirometry.

PMID- 17005057
TI  - Exhaled-breath condensate pH can be safely and continuously monitored in
      mechanically ventilated patients.
AB  - BACKGROUND: Airway inflammation in acute and chronic respiratory diseases is
      characterized in part by abnormal pH in airway-lining fluid. The pH of exhaled
      breath condensate (EBC) is low (acidic) in various pulmonary inflammatory
      diseases, including asthma, chronic obstructive pulmonary disease, cystic
      fibrosis, pneumonia, and acute respiratory distress syndrome. Because the time
      course of pH changes in the airway is not yet clear, we aimed to develop a method
      for frequent and intensive EBC pH data collection in mechanically ventilated
      patients. METHODS: We examined the collection, gas-standardizing (CO2 removal),
      and continuous monitoring of pH of EBC from the expiratory port of a Servo-i
      ventilator with mechanically ventilated patients. We developed a condensing
      device that attaches to the exhaust port and is chilled by an electric cooling
      system. We built a 2-chamber gas-standardization and pH-measuring device that
      attaches to the condensing system and records pH every 6 s. After safety testing,
      we enrolled mechanically ventilated patients (with diverse reasons for requiring
      ventilatory support) for up to 96 h of continuous EBC pH condensimetry. RESULTS:
      The pressure, volume, and flow of the ventilator attached to a test lung were
      unchanged by application of the condensimeter, at various flows (2-120 L/min) and
      ventilator settings. We monitored 19 pediatric patients for 6-96 h. The pH of the
      accumulated EBC in the storage container correlated with the geometric mean of
      all the pH data points from the condensimeter during the recording period (r2 = 
      0.95, p < 0.001), which internally validated that the condensimetry system
      provides accurate, well gas-standardized readings for up to 96 h. The EBC pH
      values were similar to published reports of single samples. The EBC pH became
      more acidic during clinical deterioration and normalized with recovery.
      CONCLUSION: Continuous monitoring of EBC pH from the ventilator exhaust port is
      safely achievable and reliably provides data that may become useful in monitoring
      critically ill patients.

PMID- 17005058
TI  - A decremental PEEP trial identifies the PEEP level that maintains oxygenation
      after lung recruitment.
AB  - OBJECTIVE: To assess the ability of a decremental trial of positive end
      expiratory pressure (PEEP) to identify an optimal PEEP level that maintains
      oxygenation after a lung-recruitment maneuver. DESIGN: Prospective clinical
      trial. SETTING: Surgical intensive care unit of a university hospital. PATIENTS:
      Twenty sedated patients with acute lung injury and/or acute respiratory distress
      syndrome, ventilated for 1.2 +/- 0.4 d. INTERVENTION: Each patient received up to
      3 lung-recruitment maneuvers with continuous positive airway pressure of 40 cm
      H2O sustained for 40 s to increase the ratio of P(aO2) to F(IO2) by > 20%.
      Following the lung-recruitment maneuver, PEEP was set at 20 cm H2O and then the
      F(IO2) was decreased until the oxygen saturation (measured via pulse oximetry
      [S(pO2)]) was 90-94%. PEEP was then decreased in 2-cm H2O steps until the S(pO2)
      dropped below 90%. The step preceding the drop to below 90% was considered the
      optimal PEEP. The lung was then re-recruited and PEEP and F(IO2) were set at the
      identified levels. The patients were followed for 4 h after the PEEP trial and
      the setting of PEEP and F(IO2). RESULTS: After the lung-recruitment maneuver, all
      the patients' P(aO2)/F(IO2) increased > 50%. The mean + SD P(aO2)/F(IO2) on the
      optimal decremental trial PEEP was 211 + 79 mm Hg, versus 135 + 37 mm Hg at
      baseline (p < 0.001), and was sustained at that level for the 4-h study period
      (227 + 81 mm Hg at 4 h). F(IO2) at baseline was 0.54 + 0.12 versus 0.38 + 0.12 (p
      < 0.001) at 4 h. PEEP was 11.9 + 3.0 cm H2O at baseline and 9.1 + 4.7 cm H2O (p =
      0.011) at 4 h. CONCLUSION: A decremental PEEP trial identifies a PEEP setting
      that sustains for 4 h the oxygenation benefit of a 40-cm H2O, 40-s lung
      recruitment maneuver.

PMID- 17005059
TI  - The effects of apparatus dead space on P(aCO2) in patients receiving lung
      protective ventilation.
AB  - BACKGROUND: Lung-protective ventilation using tidal volume (V(T)) of 4-6 mL/kg
      (predicted body weight) reduces mortality (compared with traditional V(T)) in
      patients with acute respiratory distress syndrome and acute lung injury.
      Standardized use of lower V(T) can result in respiratory acidosis and has raised
      new concerns about the appropriate configuration of the ventilator circuit,
      especially in regard to the dead space (V(D)) of the apparatus. We hypothesized
      that, with a patient receiving lung-protective ventilation, the removal of all
      apparatus dead space from the circuit would reduce P(aCO2) and allow a reduction
      in minute ventilation. METHODS: All the studied patients met the American
      European consensus-conference criteria for acute respiratory distress
      syndrome/acute lung injury, were receiving a lung-protective ventilation
      strategy, were > 18 years of age, and were hemodynamically stable. We
      prospectively tested 3 different ventilator-circuit configurations, in random
      sequence, for 15 min each: (1) standard hygroscopic heat-and-moisture exchanger
      (HME) with 15-cm flexible tubing, (2) 15-cm flexible tubing only, (3) no HME or
      flexible tubing. V(T), respiratory rate, positive end-expiratory pressure, and
      fraction of inspired oxygen were maintained constant throughout the study, and
      exhaled CO2 was measured continuously. Physiologic dead space (V(D)/V(T)) was
      calculated using the Enghoff modification of the Bohr equation. RESULTS: Seven
      patients were studied. Removal of the HME from the circuit significantly
      decreased V(D)/V(T) (by approximately 6%) and P(aCO2) (by approximately 5 mm Hg).
      Removal of both the HME and flexible tubing from the circuit reduced V(D)/V(T) by
      an additional 5%, and P(aCO2) by an additional 6 mm Hg. With both circuit
      configuration changes, minute ventilation fell from a mean of 11.51 L/min to
      10.35 L/min, and pH increased from 7.30 to 7.38. Carbon-dioxide production did
      not change significantly. CONCLUSION: In patients receiving lower-V(T)
      ventilation, removing all the apparatus V(D) from the ventilator circuit reduces
      P(aCO2) and increases pH, at a lower minute ventilation. This information will
      help guide ventilator-circuit configuration for patients receiving lung
      protective ventilation.

PMID- 17005060
TI  - Chest physiotherapy with positive airway pressure: a pilot study of short-term
      effects on sputum clearance in patients with cystic fibrosis and severe airway
      obstruction.
AB  - BACKGROUND: The periodic administration of positive airway pressure combined with
      directed cough could aid mucus clearance in patients with cystic fibrosis (CF)
      and severe airway obstruction. OBJECTIVE: To compare the short-term effect of
      positive expiratory pressure (PEP) physiotherapy via mask (mask PEP), continuous
      positive airway pressure (CPAP), and noninvasive positive-pressure ventilation
      (NPPV) physiotherapies on amount of sputum collected. METHODS: Directed cough was
      standardized for each patient and used as the control treatment. We studied 17
      patients with CF (mean +/- SD age 28 +/- 7 y) and severe airway obstruction
      (forced expiratory volume in the first second 25 +/- 6% of predicted) admitted
      for pulmonary exacerbation. Mask PEP, CPAP, NPPV, and the control treatment
      (directed cough) were administered in a random sequence. Each patient received
      each treatment twice a day (in 70-min sessions) for 2 consecutive days. We
      measured the wet and dry weight of sputum collected and the number of directed
      and spontaneous coughs during each session. Spirometry and pulse oximetry were
      conducted before and after each session. For mask PEP, CPAP, and NPPV, each
      patient gave a subjective score for the efficacy and tolerability of the
      treatment, compared to the control treatment. RESULTS: There was no statistically
      significant difference in the dry weight of sputum collected: mask PEP 0.9 +/-
      0.6 g, CPAP 0.8 +/- 0.4 g, NPPV 0.9 +/- 0.6 g, control treatment 1.0 +/- 0.8 g.
      There was a statistically significant difference in the wet weight of sputum
      collected: mask PEP 15.8 +/- 5.5 g, CPAP 13.7 +/- 5.5 g, NPPV 13.2 +/- 5.0 g,
      control treatment 14.0 +/- 5.0 g (p < 0.05), but that difference became
      nonsignificant when we took into account the number of spontaneous coughs. There
      were no statistically significant changes in the spirometry and pulse-oximetry
      values. The patients' subjective efficacy scores were similar for mask PEP, CPAP,
      and NPPV. Less fatigue was reported after NPPV and CPAP than after mask PEP.
      CONCLUSIONS: There were no differences in sputum clearance or pulmonary-function
      measures between mask PEP and short-term administration of either CPAP or NPPV
      combined with directed cough. After mask PEP these patients felt more tired than
      after CPAP or NPPV secretion-clearance therapy.

PMID- 17005061
TI  - Immediate changes in blood-gas tensions during chest physiotherapy with positive
      expiratory pressure and oscillating positive expiratory pressure in patients with
      cystic fibrosis.
AB  - OBJECTIVE: To assess and compare immediate effects of chest physiotherapy with
      positive expiratory pressure (PEP) versus oscillating PEP on transcutaneously
      measured blood-gas tensions in patients with cystic fibrosis. METHODS: Fifteen
      patients (mean age 12.5 y, range 6.9-21.5 y) participated. The treatments were
      randomized and performed on 2 separate occasions, 8 weeks apart. Spirometry was
      conducted before and after each treatment. We transcutaneously measured oxygen
      tension (P(tO2). RESULTS: There were no changes in spirometry values. During PEP,
      different trends in blood-gas tension were seen, and there were no consistent
      changes. During oscillating PEP, P(tO2) increased and P(tCO2) decreased. During
      oscillating PEP, P(tCO2) was lower and the intra-individual change in P(tCO2) was
      more pronounced than during PEP. The results obtained immediately after
      oscillating PEP showed a higher P(tO2) and a lower P(tCO2) than with PEP.
      CONCLUSION: PEP and oscillating PEP can both cause transitory effects on blood
      gases in patients with cystic fibrosis. However, oscillating PEP alters blood-gas
      tensions more than does PEP, and hyperventilation during oscillating PEP may
      reduce treatment time.

PMID- 17005062
TI  - An evaluation of a transcutaneous and an end-tidal capnometer for noninvasive
      monitoring of spontaneously breathing patients.
AB  - BACKGROUND: Since there is a growing use of analgesia and sedation in
      spontaneously breathing patients undergoing diagnostic or therapeutic
      interventions, recommendations by national societies of anesthesiologists call
      for the application of capnometry during all anesthetic procedures. METHODS: We
      compared readings from a transcutaneous capnometer (Tosca) and an end-tidal
      capnometer (Microcap Plus) to P(aCO2) measurements made via arterial-blood-gas
      analysis. We studied 30 spontaneously breathing patients who were recovering from
      general anesthesia, and we used Bland Altman analysis to compare the capnometry
      readings to the arterial-blood-gas values. Expiratory gas samples for end-tidal
      capnometry were taken either from a conventional face mask or an oral/nasal
      cannula. RESULTS: The Tosca significantly overestimates P(aCO2) (mean +/- SD
      difference 5.6 + 3.4 mm Hg). The Microcap Plus significantly underestimates
      P(aCO2) (mean +/- SD difference -14.1 +/- 7.4 mm Hg). There was no significant
      difference between the face mask and oral/nasal cannula with regard to collecting
      end-tidal samples. CONCLUSION: Both the Tosca and Microcap Plus provide just an
      approximate estimation of P(aCO2). Clinical use of these monitors can not be
      proposed under actual conditions but will be advantageous after correction of the
      limiting errors.

PMID- 17005063
TI  - The long-term stability of portable spirometers used in a multinational study of
      the prevalence of chronic obstructive pulmonary disease.
AB  - BACKGROUND: We report the performance of an ultrasound-based portable spirometer
      (EasyOne) used in a population-based survey of the prevalence of chronic
      obstructive pulmonary disease, conducted in 5 Latin American cities: Sao Paulo,
      Brazil; Mexico City, Mexico; Montevideo, Uruguay; Santiago, Chile; and Caracas,
      Venezuela (the Latin American COPD Prevalence Study [PLATINO]). METHODS: During
      the survey period (which ranged from 3 months to 6 months in the various
      locations) we collected daily calibration data from the 70 EasyOne spirometers
      used in the 5 survey cities. The calibrations were conducted with a 3-L syringe,
      and the calibration data were stored in the spirometer's database. RESULTS:
      Ninety-seven percent of the calibration volumes were within +/- 64 mL (2.1%) of
      the 3-L calibration signal. Excluding data from the first city studied (Sao
      Paulo), where one calibration syringe had to be replaced, 98% of the calibration
      checks were within +/- 50 mL (1.7%). The measured volume was affected only
      minimally by the syringe's peak flow or emptying time. CONCLUSION: In these 70
      EasyOne spirometers neither calibration nor linearity changed during the study.
      Such calibration stability is a valuable feature in spirometry surveys and in the
      clinical setting.

PMID- 17005064
TI  - Inhaled nitric oxide for acute right-ventricular dysfunction after extrapleural
      pneumonectomy.
AB  - Increased pulmonary vascular pressure and decreased right-ventricular performance
      may occur following pneumonectomy. Inhaled nitric oxide decreases right
      ventricular afterload and improves cardiac index by selectively decreasing
      pulmonary vascular resistance without causing systemic hypotension. We report the
      use of inhaled nitric oxide in a patient with acute right-ventricular dysfunction
      after extrapleural pneumonectomy.

PMID- 17005065
TI  - Chemotherapy alone in laryngeal squamous cell carcinoma.
AB  - AIMS: To evaluate the results of chemotherapy alone in patients with invasive
      squamous cell carcinoma of the larynx who have achieved a complete clinical
      response after an induction chemotherapy protocol. METHODS: A comparison of
      results in a group of complete responders managed with a chemotherapy alone
      protocol, matched with those of an incomplete responder group managed with
      conventional modalities. RESULTS: The survival rate of the complete responder
      group was significantly higher than that of the incomplete responder group. No
      statistically significant difference was noted between the two groups in terms of
      local failure and nodal recurrence. CONCLUSION: Our results confirm the fact that
      chemotherapy alone is a viable option in selected patients with carcinoma of the
      larynx who have achieved a complete clinical response after an induction
      chemotherapy protocol. This therapeutic approach allows surgery and/or radiation
      therapy to be reserved for the management of metachronous second primary tumours.

PMID- 17005066
TI  - Cognitive stimulation therapy for Alzheimer's disease: the effect of cognitive
      stimulation therapy on the progression of mild Alzheimer's disease in patients
      treated with donepezil.
AB  - BACKGROUND: There is general consensus regarding the benefit of
      acetylcholinesterase inhibitors (e.g. donepezil) in Alzheimer's disease (AD).
      However, the combined effect of acetylcholinesterase and cognitive stimulation
      therapy (CST) is still controversial. OBJECTIVE: This study examines their
      combined effect on the progression of cognitive decline in AD by comparing the
      cognitive performance of 17 AD patients treated with CST and donepezil (combined
      treatment group) and 13 AD patients treated with donepezil alone (control group).
      METHODS: Patients in the combined treatment group received 5 mg of donepezil per
      day and about 20 one-hour CST sessions for one year, whereas the control group
      received only 5 mg of donepezil per day. The first eight sessions were carried
      out once a week, and subsequent sessions were generally once every two weeks. The
      patients were evaluated for changes in cognitive ability by administering the
      Mini-mental State Examination (MMSE) before the start of CST (baseline) and about
      one year later (follow-up). RESULTS: A repeated-measure analysis of variance
      revealed a significant group x time interaction. The MMSE score decreased
      significantly in the control group, but did not change significantly in the
      combined treatment group. Three patients in the control group declined by four
      points on the MMSE, compared to none in the combined treatment group. Effect size
      (ES) in the control group was relatively large and negative, while the ES in the
      combined treatment group was close to zero. CONCLUSIONS: The results suggest the
      possibility that donepezil plus CST slowed the rate of cognitive decline more
      than the administration of donepezil alone.

PMID- 17005067
TI  - Loneliness in older persons: a theoretical model and empirical findings.
AB  - BACKGROUND: This study examines predictors of loneliness among low-income older
      adults through a framework named MODEL (Model of Depression and Loneliness),
      which we developed to address the need for a comprehensive and intervention
      oriented theory of loneliness in old age. The framework is rooted in a cognitive
      behavioral theory that conceptualizes behaviors as resulting from an interaction
      of cognitive processes and environmental events. METHODS: 161 residents of five
      independent-living buildings for low-income older adults in Maryland were
      interviewed individually. The assessments were based on the theoretical
      framework, MODEL, which describes the influences that environmental resources,
      health, and psychological factors have on loneliness and depression. RESULTS:
      MODEL explained a large percentage of the variance of both loneliness and
      depressed affect. Of all the barriers examined in the present study, our findings
      suggest that psychosocial factors/barriers have the strongest influence in the
      etiology of loneliness. CONCLUSION: In this population of low-income older
      persons, the importance of new contacts, mobility, and financial resources in
      predicting loneliness suggests that preventive social services should target
      these factors in developing opportunities for socialization.

PMID- 17005068
TI  - A systematic review of the prevalence and covariates of anxiety in caregivers of
      people with dementia.
AB  - BACKGROUND: Caregiving for people with dementia has consistently been linked with
      psychological problems, usually in terms of caregiver burden, general
      psychological distress and depressive symptomatology, while morbidity due to
      anxiety has been relatively neglected in this group. METHODS: We conducted a
      systematic review of the literature, searching electronic databases, reference
      lists, relevant systematic reviews and contacting experts in the field. We used
      Centre for Evidence Based Medicine (CEBM) criteria for inclusion and rating the
      validity of all studies that reported (1) the prevalence, predictors and
      covariates of anxiety disorders or anxiety caseness, and (2) covariates and
      predictors of the level of anxiety symptoms. RESULTS: Thirty-three studies met
      our inclusion criteria. Clinically, significant anxiety affects about a quarter
      of caregivers for people with dementia and was more common than in matched
      controls. Such caregivers have higher anxiety levels than controls, and that
      confrontative and escape avoidance coping, caregiver burden and poorer caregiver
      physical health are factors associated with higher anxiety levels from cross
      sectional studies. CONCLUSIONS: Coping style may be more associated with anxiety
      than depression while other covariates (burden and poor physical health) are
      similar to those for caregiver depression. We found no conclusive evidence about
      factors associated with anxiety disorders or predicting anxiety from longitudinal
      studies. Neither care recipient cognition nor ADL impairment; nor caregiver age
      nor duration of caring are associated with caregiver anxiety levels. Good quality
      cohort studies are needed to determine whether these factors also predict anxiety
      disorders.

PMID- 17005070
TI  - Hippocampal atrophy correlates with the severity of cognitive decline.
AB  - BACKGROUND: The aim of this study is to compare the results of magnetic resonance
      (MR) imaging, particularly the decline in hippocampal volume, of patients with
      Alzheimer's disease (AD) and mild cognitive impairment (MCI) with healthy age
      matched controls, to examine the reliability of hippocampal volumetry in the
      early diagnosis of AD and the correlation of the severity of hippocampal atrophy
      with the severity of cognitive decline. METHODS: Twenty-six AD, 22 MCI and 15
      normal cognitive status (NCS) patients were scanned with a 3 Tesla MR scanner.
      Hippocampus volumes were detected manually by Osiris 4.18. RESULTS: Multivariate
      regression analysis, which was performed to adjust the covariate effects of
      education, age, gender, hypertension and diabetes mellitus, showed that
      hippocampal atrophy was correlated with AD and MCI for right hippocampus; AD, MCI
      and age for left hippocampus independent of other parameters. A second regression
      analysis revealed that MMSE was correlated with hippocampal volume. CONCLUSIONS:
      Hippocampal volumetry can be used in early diagnosis of cognitive impairment, as
      well as grading cognitive decline.

PMID- 17005071
TI  - Prevalence of HIV infection among young adult injecting and non-injecting heroin
      users in Spain in the era of harm reduction programmes: gender differences and
      other related factors.
AB  - The aims were to assess the prevalence of HIV infection among young adult heroin
      users, including injecting heroin users (IHUs) and non-injecting heroin users
      (NIHUs), and to explore the differences by gender and other factors. The design
      was a cross-sectional cohort study between April 2001 and December 2003, which
      included 961 current heroin users (HU), aged 18-30 years: 422 in Madrid, 351 in
      Barcelona and 188 in Seville; 621 were IHUs and 340 were NIHUs. All were street
      recruited by chain referral methods. Face-to-face interviews were conducted using
      a structured questionnaire with computer-assisted personal interviewing (CAPI).
      Samples for HIV testing (dried blood spot) were collected and tested with ELISA
      and Western Blot. Bivariate, logistic regression, and classification and
      regression tree analyses were performed. The overall prevalence of HIV infection
      among IHUs was 25.8% (95% CI 22.3-29.3) [32.4% (95% CI 26.6-38.1) in Madrid,
      20.5% (95% CI 15.6-25.4) in Barcelona, and 20.6% (95% CI 9.8-31.4) in Seville],
      whereas in NIHUs it was 4.0% (95% CI 2.1-6.7), with no differences among cities.
      The prevalence was significantly higher in women than in men in NIHUs (10.9%, 95%
      CI 4.3-17.5 vs. 1.7%, 95% CI 0.5-4.2) and was non-significantly higher in IHUs
      (30.4%, 95% CI 23.0-37.8 vs. 24.1%, 95% CI 20.1-28.1). HIV prevalence in short
      term IHUs was 12.9% (CI 8.8-17.02), with no differences among cities. In the
      logistic analysis, the variables associated with infection in IHUs were ever
      having injected with used syringes (OR 3.4, 95% CI 2.2-5.3), ever having been in
      prison (OR 2.6, 95% CI 1.6-4.0), and heroin as the first drug injected at least
      weekly (OR 2.3, 95% CI 1.1-4.5). Factors positively associated with HIV infection
      in NIHUs were female sex (OR 8.7, 95% CI 2.6-29.2) and age >25 years (OR 3.1, 95%
      CI 0.9-11.1), while primary educational level was inversely associated (OR 0.26,
      95% CI 0.1-0.9). Although there are important geographic differences, HIV
      prevalence in IHUs remains high, even in short-term IHUs, whereas it was almost
      six times lower in NIHUs. The prevalence in women is higher than in men,
      particularly among NIHUs. A wide range of preventive strategies should be
      developed, aimed primarily at empowering women to negotiate safe sex.

PMID- 17005073
TI  - Situation of integrative medicine in China: results from a national survey in
      2004.
AB  - Integrative medicine (IM), usually called integrated traditional and Western
      medicine in China, which came into being in the 1950s as a new form of medicine,
      although is now developing quickly, little is known about its status and existing
      problems. So a national survey in China was conducted through questionnaire in
      2004 by Chinese Association of Integrative Medicine with the support of State
      Administration of Traditional Chinese Medicine (SATCM). The results show that, of
      all the medical professionals investigated in this survey, 91.21% and 93.52%
      respondents respectively favored IM as the best diagnostic and therapeutic
      method. Of all the patients who once went through TCM, Western medicine (WM) and
      IM therapies, 68.85%, 65.45% and 71.2% respondents respectively most appreciated
      IM, IM hospitals and IM therapeutic treatments. Most of the 6 595 respondents
      held that the optimal scientific research strategy in TCM should be integrating
      modern medical research method (n = 2 380) or modern scientific method (n = 2
      920). However, many hospitals exposed the problems in the aspects of governmental
      supports and funding supports, human resources, and domestic or international
      academic activities. These results indicated that IM is the patients' social
      needs and doctors' aspiration in China. For further development of IM, the
      enhancement of scientific research construction and assistance by policies and
      finance from the government and other institutions are urgently needed in China.

PMID- 17005074
TI  - Clinical study on effect of Garlicin in stabilizing the carotid artery
      atherosclerotic plaque in patients with primary hypertension and coronary artery
      disease.
AB  - OBJECTIVE: To investigate the effect of garlicin in treating carotid artery
      atherosclerotic plaque (CAAP) in patients with primary hypertension and coronary
      heart disease (PHT-CHD). METHODS: Seventy-nine patients with PHT-CHD were
      randomly divided into the treated group (39 patients) treated with garlicin and
      fosinopril and the control group (40 patients) treated with fosinopril alone. The
      change of CAAP was evaluated by high frequency ultrasonic examination every six
      months, and the changes of intercellular adhesion molecule-1 (ICAM-1) and high
      sensitive C-reactive protein (hs-CRP) were measured by ELISA, with the
      observation proceeding for 52 weeks totally. RESULTS: By the end of the
      experiment, the number of complex plaques, Crouse integrals, intima-media
      thickness, serum ICAM-1 and hs-CRP were significantly lower in the treated group
      than those in the control group with significant difference (P < 0.05).
      CONCLUSION: Garlicin could stabilize CAAP to a certain extent and shows a
      definite vascular protective effect in patients with PHT-CHD.

PMID- 17005075
TI  - Effects of Quyu Xiaoban Capsule on vascular endothelial function in patients with
      atherosclerosis.
AB  - OBJECTIVE: To evaluate the therapeutic effects of Quyu Xiaoban Capsule (QYXBC) on
      endothelial dependent vascular relaxation (EDVR) function in patients with
      atherosclerosis (AS) with ultrasonic technique. METHODS: Tested were the
      endothelial function and blood lipids of 42 patients with AS in the treated group
      and 30 healthy volunteers in the control group. And re-examination of these
      parameters was carried out on the AS patients after they had been treated with
      QYXBC for 10 months. RESULTS: Before treatment, the reactive hyperemia induced
      changes in artery diameter in the treated group was significantly lower than that
      in the control group (P < 0.01), while insignificant difference was found between
      the two groups in response to nitroglycerin. In the treated group after
      treatment, with D%-R improved significantly (P < 0.01), total cholesterol (TC),
      triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) decreased by
      16.3%, 5.6%, 10.2% respectively and high-density lipoprotein cholesterol (HDL-C)
      increased by 7.5%. EDVR was correlated negatively with the serum TC, LDL-C
      concentrations and the baseline brachial diameter (D(0)) (r = -0.41, -0.66, 
      0.59, respectively, all P < 0.01), but correlated positively with HDL-C (r =
      0.62, P < 0.05). The ameliorative extent of EDVR was correlated positively to the
      decreased magnitude of TC and LDL-C concentrations (r = 0.67, 0.59, both P <
      0.01). CONCLUSION: QYXBC can lower the level of blood lipids and improve
      significantly EDVR function.

PMID- 17005076
TI  - Effect of traditional chinese medicine on survival and quality of life in
      patients with esophageal carcinoma after esophagectomy.
AB  - OBJECTIVE: To explore the effect and possible mechanism of traditional Chinese
      medicine (TCM) on survival and quality of life (QOL) in patients with esophageal
      carcinoma after esophagectomy. METHODS: Adopting prospective controlled method of
      study, the authors had 128 post-esophagectomy patients, hospitalized from
      February 2001 to February 2002, randomly divided into 3 groups: the TCM group,
      treated with TCM drugs alone; the chemotherapy group, with chemotherapy alone
      applied; and the synthetic group, treated with chemotherapy combined with Chinese
      medicine. Their survival rate and QOL were compared. RESULTS: In the TCM group,
      the chemotherapy group and the synthetic group, the respective 3-year relapse and
      remote metastasis rate were 71.4%, 76.7%, 53.4%, respectively (chi(2) = 6.53, P <
      0.05); the 1-year survival rate 42.9%, 46.5%, 72.1%; 2-year survival rate 28.6%,
      27.9%, 55.8%, and 3-year survival rate 26.2%, 23.1%, 37.2%, respectively. And the
      QOL improving rate was 69.0%, 37.2%, 58.1%, respectively, all showing significant
      difference among them (chi(2) = 6.10, all P < 0.05). Moreover, immune function
      was increased in the TCM and the synthetic groups. CONCLUSION: Integrative
      Chinese and Western medicinal treatment was the beneficial choice for post
      operational patients with esophageal carcinoma. However, long time use of simple
      Chinese medicine was also advisable, especially for those in poverty.

PMID- 17005077
TI  - Clinical research on nourishing yin and unblocking meridians recipe combined with
      opioid analgesics in cancer pain management.
AB  - OBJECTIVE: To investigate the analgesic effects of Nourishing yin and Unblocking
      meridians Receipe (NUR) combined with opioid analgesics in managing cancer pain.
      METHODS: All the patients enrolled were differentiated as of yin deficiency and
      meridian blocked syndrome type of TCM. Forty-one of them in the treated group
      were treated with NUR combined with opioid analgesics, while 43 of them in the
      control group were given opioid analgesics alone with successive 14 days as one
      treatment course for both groups. RESULTS: The indexes of the treated group were
      superior to those in the control group as to the degree of pain-relieving, the
      therapeutic effect of analgesia, the occurrence frequency of cancer pain every
      day and its duration each time, the analgesic initial time, and the quality of
      life. CONCLUSION: NUR combined with opioid analgesics in cancer pain management
      was more effective than opioid analgesics alone.

PMID- 17005078
TI  - Effects of Erigeron injection on vascular endothelium in patients after
      intracoronary stenting.
AB  - OBJECTIVE: To observe the levels of serum C-reactive protein (CRP), endothelin-1
      (ET-1), nitric oxide (NO), and superoxide dismutase (SOD) in patients after
      intracoronary stenting (ICS), and the effects of Erigeron Injection (EI) on them.
      METHODS: Seventy-two patients, who received ICS and had symptoms of chest
      stuffiness, palpitation and chest pain, were randomly divided into two groups,
      with 36 patients in the control group treated with Plavix alone for anti-platelet
      aggregation, and the other 36 patients in the treated group treated with Plavix
      and EI in combination. CRP, ET-1, NO and SOD were determined and compared before
      and 1, 2 and 3 weeks after treatment. RESULTS: As compared with those in the
      control group, improvement of symptoms in the treated group was significantly
      better, with the levels of CRP and ET-1 lower and levels of SOD and NO higher or
      approaching to normal ranges and significant difference was shown between the two
      groups (P < 0.01). CONCLUSION: EI could alleviate uncomfortable feelings such as
      chest stuffiness in patients after ICS, and improve the function of vascular
      endothelium.

PMID- 17005079
TI  - Effect of Gutai Decoction on the abortion rate of in vitro fertilization and
      embryo transfer.
AB  - OBJECTIVE: To study the effect of Chinese herbal medicine Gutai Decoction (GTD)
      on the abortion rate of in vitro fertilization and embryo transfer (IVF-ET).
      METHODS: Observed were two hundred and forty-seven women having received IVF-ET
      and with beta-human chorionic gonadotropin (beta-HCG) > 25 IU/L on the 14th day
      after transferring. All were treated conventionally with progesterone 20 - 80 mg
      per day after transferring and if necessary the treatment was supplemented with
      Progynova 2 - 4 mg per day, with the medication withdrawn gradually from the 9th
      week of pregnancy till stopped completely. Among them 131 cases received GTD
      medication additionally, for 109 cases of whom the medication started from the
      2nd day of transferring (taken as Group A) and for the other 22 cases from the
      14th day after transferring (taken as Group B), the other 116 cases with no
      additional GTD treatment given were taken as the control group, with the
      medication lasting to the 12th week. The abortion rate in them was observed.
      RESULTS: The abortion rate in Group A, Group B and the control group was 12.84%,
      13.64% and 23.28%, respectively, the difference between the GTD treated groups
      and the control group was significant (P < 0.05). CONCLUSION: Chinese medicine
      GTD could reduce abortion rate in women receiving IVF-ET.

PMID- 17005080
TI  - Effects of serum containing Xinlikang on angiotensin ii induced hypertrophy in
      cultured neonatal rat cardiomyocytes.
AB  - OBJECTIVE: To evaluate the effects of Xinlikang (XLK) on angiotensin II (Ang II)
      induced hypertrophic cultured neonatal rat's cardiomyocyte (CMC). METHODS:
      Primary cultured neonatal rat's CMCs with the purity certified by
      immunohistochemical technique, were divided into three groups. Rats in the normal
      control group were untreated; those in the model group were established into
      hypertrophic models but underwent no treatment; and those in the XLK group were
      established to hypertrophic models and treated with XLK containing serum obtained
      from rats with aorta coarctation after 8 days of feeding with XLK. MTT and phase
      contrast microscope were used to evaluate the effect of XLK on cell activity,
      pulsating rhythm and surface area; Atrial natriuretic peptide (ANP) expression
      was determined by radioimmunoassay; Protein content was determined by Bradford
      method; and DNA synthesis was detected by flow cytometric assay. RESULTS:
      Immunohistochemistry results showed that more than 90% of the cells were alpha
      sarcometin actin stained positive cells. No significant effect of XLK on normal
      CMC was found. Ang II could significantly induce hypertrophy in CMCs, and XLK
      could significantly decrease the increased surface area and the accelerated
      pulsating rate in them. ANP expression was 780 +/- 38 microg/L in the model
      group, and 430 +/- 23 microg/L in the control group, and the elevated expression
      of ANP in model rats was significantly decreased in the XLK group; The DNA
      content in the G0/G1 and G2/M phases was significantly enhanced and at the same
      time it was accompanied with increase of total protein content in the model rats
      after being stimulated by Ang II for 24 h, showing that serum-containing XLK
      could also significantly suppress total protein synthesis (P < 0.05). CONCLUSION:
      XLK could improve Ang II mediated pathological growth of CMCs without influencing
      the growth of normal CMCs, suggesting that XLK is probably an effective drug for
      treatment of myocardial hypertrophy and heart failure.

PMID- 17005082
TI  - Attenuation of brain inflammatory response after focal cerebral
      ischemia/reperfusion with Xuesaitong injection in rats.
AB  - OBJECTIVE: To investigate the neuro-protective effect of Xuesaitong Injection
      (XST) on brain inflammatory response after transient focal cerebral
      ischemia/reperfusion in rats. METHODS: Focal cerebral ischemia/reperfusion models
      of male rats were induced by transient occlusion for 2 h of middle cerebral
      artery (MCA) which was followed by 24 h reperfusion. XST was administered through
      intraperitoneal injection of 25 mg/kg or 50 mg/kg at 4 h after the onset of
      ischemia. After reperfusion for 24 h, the neurological function score was
      evaluated, the brain edema was detected with dry-wet weight method, the
      myeloperoxidase (MPO) activity and the expression of intercellular adhesion
      molecule-1 (ICAM-1) of ischemic cerebral cortex and caudate putamen was
      determined by spectrophotometry and immunohistochemistry respectively. RESULTS:
      XST not only lowered neurological function score at the dose of 50 mg/kg, but
      reduced brain edema and inhibited MPO activity and ICAM-1 expression as compared
      with the ischemia/reperfusion model group (P < 0.01). CONCLUSION: XST has a
      definite effect on inhibiting the expression of ICAM-1 and neutrophil
      infiltration in rats with cerebral ischemia/reperfusion when treatment started at
      4 h after ischemia onset, and also attenuates inflammation in the infarcted
      cerebral area.

PMID- 17005081
TI  - Cardio-protective effects of Corocalm on acute myocardial ischemia/reperfusion
      injury in rats.
AB  - OBJECTIVE: To investigate the cardio-protective effects of Corocalm on acute
      myocardial ischemia in rats, and to explore its possible therapeutic mechanisms.
      METHODS: The acute ischemic model was prepared by ligating the left anterior
      descending (LAD) coronary artery in rats. The animals were divided into 6 groups,
      8 in each group. The sham operated group underwent heart exposure without
      ligation and were treated with normal saline 3 ml/kg, while the other 5 groups,
      the model groups, consisted of acceptable acute ischemic model rats and were also
      treated with normal saline, with the Guanxin Capsule (GXC) group treated with
      refined GXC, 600 mg/kg, the low and high dose Corocalm groups treated with 85
      mg/kg and 340 mg/kg of Corocalm respectively, and the Diltiazem group, treated
      with Diltiazem 5 mg/kg, with all the tested drugs prepared with normal saline
      into equal volume (3 ml/kg) and administrated once via duodenum 10 min before
      ligation. Myocardial infarction area was determined by the quantitative
      histological assay with nitroblue tetrazolium (N-BT) stain. And the levels of
      creatine phosphokinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA)
      content, and the activity of superoxide dismutase (SOD) in serum were measured by
      biochemical assay and spectrophotometry respectively. Besides, the blood
      viscosity in another 50 rats was determined, who received for 7 successive days
      oral administration with different concentration of Corocalm or aspirin. RESULTS:
      It showed that low and high dose Corocalm could significantly reduce the
      infarction area, inhibit the increase of serum CK, LDH activity and MDA content,
      and enhance the SOD activity after ischemia/reperfusion. The whole blood
      viscosity at different shear rates in rats treated with high dose Corocalm was
      significantly lower than those treated with normal saline (P < 0.05). CONCLUSION:
      Corocalm has favourable protective effects on heart in ischemic condition, the
      effect of which might be through its actions in inhibiting CK and LDH activity,
      scavenging oxygen free radicals, and lowering blood viscosity.

PMID- 17005083
TI  - Study on effects of extracts from Salvia Miltiorrhiza and Curcuma Longa in
      inhibiting phosphorylated extracellular signal regulated kinase expression in
      rat's hepatic stellate cells.
AB  - OBJECTIVE: To study the effect of salvianolic acid B (SAB) and curcumin, the
      extracts of Salvia Miltiorrhiza and Curcuma Longa, on the proliferation and
      activation of hepatic stellate cell (HSC), and the extracellular signal regulated
      kinase (ERK) expression in it. METHODS: Rat's HSC-T6 were cultured and treated by
      SAB or curcumin. The inhibitory effect on cell proliferation was determined by 3
      (4, 5-dimthyl-2-2thiazoly)-2, 5-diphenyl-2H-tetrazolium bromide (MTT)
      colorimetry, and the expression levels of alpha smooth actin (alpha-SMA),
      collagen type I, and ERK were determined by Western blot. RESULTS: SAB and
      curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose
      dependent fashion and significantly reduced the expression level of alpha-SMA (P
      < 0.01). Curcumin significantly reduced the expression of collagen type I (P <
      0.05). Both SAB and curcumin showed insignificant effect on the ERK expression
      level, but they could significantly reduce the level of phosphorylated-ERK
      expression, showing significant difference as compared with that in the control
      group (P < 0.01 and P < 0.05 respectively). CONCLUSION: SAB and curcumin could
      significantly inhibit the proliferation, activation of HSC, and the production of
      type I collagen in HSC, the mechanism may be associated with their inhibition on
      ERK phosphorylation.

PMID- 17005084
TI  - Comparative study on treatment of acute gouty arthritis by electroacupuncture
      with different frequency.
AB  - OBJECTIVE: To study the therapeutic effect of treatment of acute gouty arthritis
      (AGA) respectively by electroacupuncture (EA) with different frequency and oral
      intake of Western medicine. METHODS: Seventy-two patients of AGA were randomly
      assigned into three groups, 24 in each group. Group A was treated with EA 100 Hz;
      Group B with EA 2 Hz; and Group C with Western medicine. The analgesic effect,
      initiating time and sustaining time of analgesia were observed and the level of
      serum uric acid was measured before and after treatment. RESULTS: The initiating
      time of analgesia was shorter while the sustaining time of analgesia was longer
      in Group A and B than those in Group C (all P < 0.01). The efficacy of analgesia
      was higher in Group B than that in Group A, and a better effect was shown in
      Group B in reducing serum uric acid level than that in Group A (P < 0.01), which
      was near that in Group C (P > 0.05). CONCLUSION: EA is an effective treatment for
      AGA, and low frequency (2 Hz) EA showed a better efficacy.

PMID- 17005085
TI  - Clinical observation on effect of Kaixin capsule in treating 40 patients with
      diabetic myocardial ischemia.
AB  - OBJECTIVE: To observe the effect of Kaixin Capsule (KXC) on myocardial ischemia
      and plasma endothelin (ET) level in patients with diabetic heart disease (DHD).
      METHODS: The 72 subjects for observation were randomly selected from inpatients
      whose diagnosis fit to the standard of DHD. The 32 patients allocated in the
      control group were treated with conventional Western medicine, and the 40
      patients in the treated group were treated with conventional Western medicine in
      combination with KXC, with the therapeutic course for both groups as 60 days.
      RESULTS: On ECG, the total effective rate and markedly effective rate in the
      treated group was 85.0% and 37.5% respectively, higher than those in the control
      group's 68.7% and 28.1% respectively, and showing significant difference between
      the two groups (P < 0.05). The level of ET in patients in both groups was
      significantly higher than normal range, after treatment, but reduced to different
      extent, and the comparison between them also showed that the difference was
      significant (P < 0.05). CONCLUSION: KXC might, by way of inhibiting and blocking
      the release of ET, lower its level in plasma so as to improve the myocardial
      ischemic condition of patients with DHD.

PMID- 17005086
TI  - Comparative study on the efficacy of Yiweining and Gestrinone for post
      operational treatment of stage III endometriosis.
AB  - OBJECTIVE: To observe the clinical efficacy and safety of Yiweining (YWN) and
      gestrinone (GT) in treating post-operational patients of stage III endometriosis
      (EM-III). METHODS: Fifty-two patients of EM-III after operation were randomly
      assigned into three groups, the YWN group (20 patients) was treated through oral
      intake of YWN 200 ml, twice a day; the GT group (19 patients) treated with
      gestrinone 2.5 mg, twice every week, with the medication starting from the 7th
      post-operational day and lasting for 6 months. The control group (13 patients)
      was untreated. Six months was one therapeutic course, and follow-up study was
      carried out in the 6 - 30 months after the end of the medication. RESULTS: The
      recurrence rate in the YWN group and the GT group were 5.0% and 5.3%
      respectively, showing insignificant difference between the two groups, but they
      were lower than that in the control group (30.7%, P < 0.05). Besides, the adverse
      reaction rate in the YWN group was lower than that in the GT group (10.0% vs
      31.6%, P < 0.05). CONCLUSION: Application of YWN to prevent the post-operational
      recurrence of endometriosis is effective and safe, and its efficacy is similar to
      that of GT.

PMID- 17005087
TI  - Effect of Simotang oral liquid on anal exhaust in patients after abdominal
      gynecological operation.
AB  - OBJECTIVE: To study the effect of Simotang oral liquid and glycerin enema on the
      patients' bowel sound (BS) restoration and anal exhaust after abdominal
      gynecological operation. METHOD: Ninety patients with benign tumor who had
      undergone gynecological operation were randomly divided into the Simotang group,
      treated after operation with Simotang oral liquid; the enema group, treated with
      glycerin enema, and the control group, non-treated. The restoration time of BS
      and anal exhaust were observed. RESULTS: Compared with the control group, the
      restoration time of BS and anus exhaust were both significantly shorter in the
      Simotang group and the enema group, showing statistical significance (P < 0.05);
      but the difference between the two treated groups was insignificant (P > 0.05).
      CONCLUSION: Simotang oral liquid and glycerine enema both could benefit the
      restoration of anal exhaust and BS after abdominal operation.

PMID- 17005088
TI  - Concerning the use of Western medical terms to represent traditional Chinese
      medical concepts.
AB  - This paper strongly rejects the notion that the use of biomedical terms to
      represent traditional Chinese medical concepts is helpful to the
      internationalization of Chinese medicine. It further argues that this practice
      destroys the integrity and independence of Chinese medical concepts. Taking the
      term feng huo yan as an example, it shows that the biomedical term "acute
      conjunctivitis" often suggested as the translation for this term is
      unsatisfactory, because (1) the clinical reference is not identical, (2) it
      introduces the concepts of "conjunctiva" and "inflammation" , which are not
      Chinese medical concepts, and (3) destroys the Chinese medical concepts "wind"
      and "fire" expressed in the Chinese, which reflect the way the disease is
      traditionally diagnosed and treated. While for English readers not familiar with
      Chinese medicine, "acute conjunctivitis" may be immediately intelligible, for
      those seeking a deep understanding of the subject, the literal translation (loan
      translation) "wind-fire eye" is much more helpful. This paper supports these
      arguments with numerous other examples.

PMID- 17005089
TI  - Survey of current experimental studies of effects of traditional chinese medicine
      on peripheral nerve regeneration.
AB  - The repairing and regeneration of peripheral nerves is a very complex biological
      and cytological process, its mechanism is unclear so far, and thus results in the
      lack of specific and effectual therapy and medicament. Chinese herbs and their
      effective components have their own inimitable predominance in promoting
      peripheral nerve regeneration, such as their multi-factorial, multi-target and
      multi-functional action, abundant source, inexpensive, etc. In this paper, the
      experimental studies reported in recent 5 years concerning the effects of Chinese
      herbs or their active components on peripheral nerve repairing and regeneration
      are reviewed in respects of the integral level, cellular level, molecular level
      and gene level.

PMID- 17005091
TI  - Employee's well-being a manager's responsibility.

PMID- 17005090
TI  - Progress in researches on the pharmaceutical mechanism and clinical application
      of Ginkgo Biloba extract on various kinds of diseases.
AB  - Progress made over the pharmaceutical mechanism and clinical application of
      Ginkgo Biloba extract (GBE) on various kinds of diseases were reviewed in this
      paper. The effective elements contained in GBE are mainly kinds of Ginkgo
      flavonoid and Ginkgolide, which have marked protective effects on cardio-cerebral
      vascular and central nerve systems. In clinical practice, it is applied mostly in
      treatment of cardio-cerebral vascular diseases. Also it shows apparent effects in
      the treatment processes of some other diseases as an adjuvant, and therefore, has
      been gradually accepted by the medical circle in the world, proving to be a
      medicine of wide prospect in development and application.

PMID- 17005093
TI  - Pro: lean six sigma revolutionizing health care of tomorrow.

PMID- 17005094
TI  - Con: six sigma not always the right answer in the clinical laboratory.

PMID- 17005095
TI  - Pre-analytic process control: projecting a quality image.
AB  - Within the health-care system, the term "ancillary department" often describes
      the laboratory. Thus, laboratories may find it difficult to define their image
      and with it, customer perception of department quality. Regulatory requirements
      give laboratories who so desire an elegant way to address image and perception
      issues--a comprehensive pre-analytic system solution. Since large laboratories
      use such systems--laboratory service manuals--I describe and illustrate the
      process for the benefit of smaller facilities. There exist resources to help even
      small laboratories produce a professional service manual--an elegant solution to
      image and customer perception of quality.

PMID- 17005096
TI  - Managing hazardous waste in the laboratory.
AB  - This article offers an introduction to the federal U.S. Environmental Protection
      Agency (EPA) regulations as they relate to hazardous wastes generated by clinical
      and anatomic pathology laboratories. Traditionally, the EPA has targeted "heavy"
      industries such as manufacturing for compliance auditing, but it recently turned
      an eye toward health-care facilities since they are identified as important
      sources of hazardous waste generation. Enforcement of EPA regulations within
      health-care facilities presents the challenge of a new labyrinth of definitions,
      rules, and compliance methods for laboratorians who have already made it through
      other regulatory agency mazes, including the Joint Commission on Accreditation of
      Healthcare Organizations (JCAHO) standards, the College of American Pathologists
      (CAP) checklists, and the Occupational Safety and Health Administration (OSHA)
      standards.

PMID- 17005097
TI  - Chemical hygiene training standards.

PMID- 17005098
TI  - Turn your techs into Super Techs--part two.

PMID- 17005099
TI  - Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and
      neuroimaging correlates.
AB  - We assessed the structural and functional imaging features of cerebellar lesions
      and their neurobehavioral correlates in a large cohort of patients with tuberous
      sclerosis complex. A consecutive series of 78 patients with tuberous sclerosis
      complex underwent magnetic resonance imaging (MRI) and positron emission
      tomography (PET) studies with [(18)F]fluorodeoxyglucose (FDG) and alpha
      [(11)C]methyl-l-tryptophan (AMT) as part of their evaluation for epilepsy
      surgery. Neurobehavioral assessment included the Gilliam Autism Rating Scales
      (GARS) and the Vineland Adaptive Behavior Scales (VABS). Twenty-one patients
      (27%) had cerebellar lesions (10 boys; mean age 9 +/- 8 years; 9 had right-sided,
      10 had left-sided, and 2 had bilateral cerebellar lesions). The lesions showed
      decreased glucose metabolism (0.79 +/- 0.10) and increased (1.04 +/- 0.10) AMT
      uptake compared with the normal (nonlesional) cerebellar cortex. Comparisons
      between patients with (n = 20) and without (n = 57) a cerebellar lesion on
      neurobehavioral functioning, controlling for the number and location of cortical
      tubers, revealed that the cerebellar lesion group had higher overall autistic
      symptomatology. Within-group analyses of the cerebellar lesion group revealed
      that children with right-sided cerebellar lesions had higher social isolation and
      communicative and developmental disturbance compared with children with left
      sided cerebellar lesions. The side of the cerebellar lesion was not related to
      adaptive behavior functioning. These findings provide additional empiric support
      for a role of the cerebellum in autistic symptomatology. Further investigation of
      the potential role of the right cerebellum in autism, particularly with regard to
      the dentatothalamofrontal circuit, is warranted.

PMID- 17005100
TI  - Acute disseminated encephalomyelitis in North Indian children: clinical profile
      and follow-up.
AB  - Acute disseminated encephalomyelitis in children is not uncommon in developing
      countries, yet there is little systematic documentation of its clinical profile
      and follow-up. We studied the clinical and neuroradiologic features of acute
      disseminated encephalomyelitis in 52 consecutive children. Clinical details,
      magnetic resonance imaging (MRI) findings, and the results of other
      investigations were recorded, and children were followed up from 6 to 48 months.
      A repeat MRI was done after 3 to 4 months, and in those with persistent lesions,
      another MRI was done after 6 to 7 months of discharge. The mean age at
      presentation was 6.14 +/- 3.17 years, 73.1% were male, and 17 children had a
      history of antecedent infectious illness or vaccination. Most children had a
      meningoencephalitic presentation, with sudden-onset motor weakness in 76.9% and
      seizures in 36.5%. Altered sensorium and pyramidal signs were seen in 55.8% and
      80.7% of children, respectively. On MRI, scattered T(2)-weighted hyperintense
      lesions were seen, mainly in the subcortical white matter, especially in the
      parietal (53.8%) and frontal (30.17%) regions. Thalamic, basal ganglia, and
      callosal lesions were seen in 30.76%, 17.3%, and 13.46% of cases, respectively.
      Variable contrast enhancement was seen in 48% of those who had contrast MRIs. The
      response to methylprednisolone was good, with dramatic recovery in 26.9% and
      marked improvement in 51.9% at discharge. On follow-up, of 44 children, residual
      smaller MRI lesions were seen in 30. The MRI was repeated at 6 months in children
      with residual lesions, and it was found that the lesions either disappeared or
      were significantly reduced after 6 months in 75% of cases. Four children had
      relapse of acute disseminated encephalomyelitis with new lesions on MRI. All of
      them responded to methylprednisolone. None of the clinical or neuroradiologic
      factors at presentation had any significant correlation with relapse. Six months
      after discharge, no deficits could be found in 61.3% of cases; 15.9% and 4.5% had
      motor and cognitive deficits, and 9% had multiple deficits. The presentation of
      pediatric acute disseminated encephalomyelitis in developing countries is similar
      to that in developed countries. In spite of an aggressive presentation, most
      children respond well to corticosteroids. MRI lesions disappear or are
      significantly reduced at 6 months in the majority of cases.

PMID- 17005101
TI  - Deep sedation with propofol in patients with Rett syndrome.
AB  - Herein we present the largest retrospective case-control series of deep sedation
      in patients with Rett syndrome, including discussion of the unique aspects of
      Rett syndrome that make these patients at high risk for sedation. Twenty-one
      patients with Rett syndrome and 21 control patients who received propofol for
      deep sedation to facilitate lumbar puncture were compared. Patients with Rett
      syndrome required significantly less propofol than control patients when
      standardized for weight and the duration of the procedure (P = .004). Seven of
      the 21 patients with Rett syndrome compared with none of the control patients
      experienced a serious adverse event, most of which were due to prolonged apnea (P
      = .004). All adverse events were transient, and all patients returned to their
      baseline after the procedure was completed. Sedation of patients with Rett
      syndrome is associated with a relatively high rate of complications and should
      not be done without appropriate personnel available who recognize the risks of
      sedating this unique population.

PMID- 17005102
TI  - Intractable epilepsy secondary to cyclosporine toxicity in children undergoing
      allogeneic hematopoietic bone marrow transplantation.
AB  - The long-term evolution to intractable epilepsy in children treated with
      cyclosporine administered for graft-versus-host-disease after hematopoietic stem
      cell transplantation was evaluated. In a group of 185 children treated with
      cyclosporine after bone marrow transplantation, 15 (8%) presented with acute
      seizures that were generalized in 7 and focal in 7 and had absence status in 1.
      Electroencephalography (EEG) and neuroimaging showed predominant abnormalities in
      the occipital regions. One patient died shortly after the seizure; in seven
      cases, seizures remitted, whereas relapses were observed in seven others. After
      the first year, seizures persisted chronically in four cases and evolved to
      intractable epilepsy. Focal temporal epilepsy was diagnosed in three cases,
      whereas in the fourth case, a multifocal epilepsy was observed. Magnetic
      resonance imaging (MRI) detected mesial temporal sclerosis in all of these cases.
      The risk factors associated with evolution to epilepsy included lower age at
      transplantation (3-5 years), more than one relapsing seizure in the first year
      after transplantation, and longer treatment with cyclosporine. Not only can
      cyclosporine cause acute central nervous system toxicity, it can also determine
      intractable epilepsy associated with mesial temporal sclerosis.

PMID- 17005103
TI  - Magnetic resonance imaging study of the orbitofrontal cortex in autism.
AB  - The orbitofrontal cortex is involved in multiple psychologic functions, such as
      emotional and cognitive processing, learning, and social behavior. These
      functions are variably impaired in individuals with autism. The present study
      examined the size of the orbitofrontal cortex, and its medial and lateral
      subdivisions, using magnetic resonance imaging (MRI) scans obtained from 40 non
      mentally retarded individuals with autism and 41 healthy controls. No differences
      were observed between the two groups on any of the orbitofrontal cortex
      measurements. However, when compared with controls, a smaller right lateral
      orbitofrontal cortex was observed in children and adolescents with autism,
      whereas a larger right lateral orbitofrontal cortex was found in adult patients.
      Interestingly, a positive relationship was found in the patient group between
      circumscribed interests and all orbitofrontal cortex structures. The present
      study suggests the absence of global volumetric abnormalities in the
      orbitofrontal cortex in autism and indicates that the functional disturbances in
      this structure might not be related to anatomic alterations.

PMID- 17005104
TI  - Acute necrotizing encephalopathy of childhood in non-Asian patients: report of
      three cases and literature review.
AB  - Acute necrotizing encephalopathy of childhood is a novel type of parainfectious
      encephalopathy with a racial and geographic predilection, rarely reported from
      other than East Asian areas. The objective was to describe the clinical, imaging,
      and other laboratory findings of non-Asian patients with acute necrotizing
      encephalopathy. Data were collected from three patients diagnosed in Athens over
      a 4-year period plus 16 cases reported from other European and North American
      countries. One of the Greek children died, and the other two had a normal
      outcome. A neuropathologic examination in the fatal case showed edematous
      necrosis without inflammatory, reactive, or proliferative changes. Data from
      Greek and other non-Asian patients support the homogeneity of the disease
      worldwide.

PMID- 17005105
TI  - Dopamine agonist therapy in low-response children following traumatic brain
      injury.
AB  - The objective of this study was to determine whether a dopamine agonist could
      improve mental status among children in a low-response state following traumatic
      brain injury. In an 8-week, prospective, double-blind, randomized trial, 10
      children and adolescents ages 8 to 21 years (X = 16.7 years) with traumatic brain
      injury sustained at least 1 month previously and remaining in a low-response
      state (Rancho Los Amigos Scale level pound 3) received pramipexole or amantadine.
      Medication dosage was increased over 4 weeks, weaned over 2 weeks, and then
      discontinued. At baseline and weekly during the study, subjects were evaluated
      with the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and
      Disability Rating Scale. Scores improved significantly from baseline to the
      medication phase on the Coma Near Coma Scale, Western NeuroSensory Stimulation
      Profile, and Disability Rating Scale (P < .005). The weekly rate of change was
      significantly better for all three measures on medication than off medication (P
      < .05). Rancho Los Amigos Scale levels improved significantly on medication as
      well (P < .05). There was no difference in efficacy between amantadine and
      pramipexole. No unexpected or significant side effects were observed with either
      drug. This clinical trial supports the benefit of two dopamine agonists in the
      restoration of functional arousal, awareness, and communication. These drugs can
      be helpful in accelerating eligibility for acute rehabilitation among children
      and adolescents who have sustained significant brain injuries.

PMID- 17005106
TI  - Remission associated with human herpesvirus infection in west syndrome.
AB  - Generally, West syndrome is an intractable epileptic syndrome in infancy,
      although spontaneous remission has been reported in some cases. An immunologic
      response to infection might be one of the factors involved in the remission of
      West syndrome, but the mechanisms remain unknown. On the other hand, exanthema
      subitum is a common disease occurring in infancy with the characteristics of
      fever and rash. Two kinds of human herpesvirus, 6 and 7, have been isolated as
      causal agents of exanthema subitum. We experienced one symptomatic case and three
      cryptogenic cases of West syndrome that showed spontaneous remission. In the
      symptomatic case, the subject showed a temporary remission; however, in the other
      cases, the remissions were long term. In the present study, we report the
      patients' improvement and electroencephalographic (EEG) findings. In all of our
      cases, hypsarrythmia disappeared on the EEG findings, the human herpesvirus 6 IgG
      antibodies increased in all four cases, and the herpesvirus 7 IgG antibodies
      increased in two cases. We postulate that the remission of the four cases
      proceeded from infection by exanthema subitum. The changes in serum antibody
      values suggest that the spontaneous remission of West syndrome was related to
      human herpesvirus 6 and 7 infections.

PMID- 17005107
TI  - Acute childhood hemiplegia associated with chickenpox and elevated
      anticardiolipin antibody.
AB  - Chickenpox is a common infection of childhood. Central nervous system
      complications, such as cerebellar ataxia and meningoencephalitis, are estimated
      to occur in less than 1% of cases of chickenpox. Although transverse myelitis and
      hemiplegia have also, although rarely, been reported, hemiplegia associated with
      chickenpox and elevated anticardiolipin antibody has not been reported in the
      literature. We report the case of a 2.5-year-old boy who developed a right
      hemiplegia 3 weeks after the onset of a primary varicella infection. The serum
      level of anticardiolipin antibody IgG was markedly elevated. Brain magnetic
      resonance imaging (MRI) revealed an infarction involving the left globus
      pallidus, caudate nucleus, and posterior leg of the internal capsule. Laboratory
      studies ruled out all known causes of stroke. Neurologic signs and symptoms
      slowly improved with supportive treatment. Varicella infection should be
      considered one of the possible causes of acute ischemic strokes in children.
      Usually, two or more risk factors are detected in children with ischemic strokes,
      and we suggest that all possible causes of strokes be investigated in children
      with ischemic strokes.

PMID- 17005108
TI  - Megalocornea and mental retardation syndrome: clinical and instrumental follow-up
      of a case.
AB  - Megalocornea-mental retardation syndrome, otherwise known as Neuhauser syndrome,
      is a rare autosomal recessive disorder. Only 36 cases have been reported in the
      literature. We describe the clinical and instrumental follow-up, lasting 5 years,
      of a case showing the typical features of the syndrome, associated with transient
      hypothyroidism, epilepsy, cerebral palsy with choreoathetotic movements, and
      brain malformation. Our report might help better delineate the phenotype and
      natural history of the syndrome.

PMID- 17005109
TI  - Should we routinely perform blood tests in children with uncontrolled seizures?
AB  - The value of biochemical tests in treating patients with uncontrolled seizures is
      unclear. We present the case of an 8-year-old boy with uncontrolled seizures
      receiving two antiepileptic drugs. He had been diagnosed with recurrent herpes
      encephalitis and treated with acyclovir 1 year previously. Laboratory blood
      analyses, performed because of his uncontrolled seizure episodes, revealed
      hypocalcemia. Hypoparathyroidism was detected with elevated levels of phosphorus
      and low levels of parathormone. In conclusion, blood tests, especially to measure
      calcium, in children with uncontrolled seizures are suggested. Hypoparathyroidism
      causing hypocalcemia, as present here, is not a rare occurrence.

PMID- 17005110
TI  - Popliteal angle in infants with west syndrome.
AB  - The aim of this study was to clarify the relationship between neurologic findings
      and outcome of patients with West syndrome, focusing on the popliteal angle. The
      complete neurologic examination, including an assessment of the popliteal angle
      and muscle tone, was performed on 45 patients with West syndrome. A tight
      popliteal angle was determined when it was 120 degrees or less. In all 45
      patients, abnormal muscle tone was not correlated with any variables. A tight
      popliteal angle was correlated with seizure persistence, cerebral palsy, and
      abnormality on magnetic resonance imaging (MRI), as well as severe developmental
      delay. When limited to the patients with developmental delay, a tight popliteal
      angle was correlated with severe developmental delay, cerebral palsy, and MRI
      abnormality, although abnormal muscle tone was not correlated with any items. In
      the delay group, eight patients had a tight popliteal angle with normal muscle
      tone. Among them, severe developmental delay was seen in seven (88%), seizure
      persistence in five (63%), and MRI abnormality in five (63%). These results
      suggest that a tight popliteal angle might be an indicator of poor neurologic
      outcome in patients with West syndrome.

PMID- 17005111
TI  - Transient nonketotic hyperglycinemia and defective serotonin metabolism in a
      child with neonatal seizures.
AB  - Neonatal nonketotic hyperglycinemia is usually fatal or, less commonly, severely
      developmentally disabling, whereas transient nonketotic hyperglycinemia has
      usually been followed by normal development. We report a boy who had transient
      neonatal nonketotic hyperglycinemia but a coexistent disorder of serotonin
      metabolism manifested by initially low cerebrospinal fluid 5-hydroxyindoleacetic
      acid (which later normalized), low whole blood serotonin, and decreased platelet
      serotonin uptake. He survived the neonatal period but was neurodevelopmentally
      delayed and developed an autistic-like disorder. Later, his positron emission
      tomographic (PET) scans with alpha[(11)C] methyl-l-tryptophan revealed a pattern
      characteristic of autistic children. Although we know of no link between glycine
      and serotonin metabolism, and our patient had low, rather than high, central and
      peripheral serotonin, this case might represent a novel infantile disorder that
      affects both the glycine and serotonin neurotransmitter systems.

PMID- 17005112
TI  - Different additional risk factors for cerebral infarctions associated with the
      factor V Leiden mutation in a family.
AB  - Several cases with cerebral infarctions associated with the factor V Leiden
      mutation have been reported. However, bearing in mind the large number of
      asymptomatic individuals with the factor V Leiden mutation, additional risk
      factors for cerebral infarctions should be considered. In this report, two
      siblings with cerebral infarctions associated with a combination of heterozygous
      factor V Leiden mutation and different additional exogenous and endogenous
      thrombogenic risk factors are described. Respiratory problems in the perinatal
      period and increased lipoprotein (a) concentrations in the first patient and an
      episode of gastroenteritis from Shigella infection and persistent high titers of
      serum anticardiolipin and beta(2)-glycoprotein I antibodies in the second patient
      were recorded as additional thrombogenic risk factors. Furthermore, both patients
      were found to be heterozygous for the methylenetetrahydrofolate reductase gene
      C677T mutation. These findings suggest that even in the same family, different
      additional thrombogenic risk factors can be present in infants with cerebral
      infarctions associated with the factor V Leiden mutation. An extensive search of
      additional circumstantial and genetic thrombogenic risk factors should be useful
      for prophylaxis and prognosis of these infants with cerebral infarctions
      associated with the factor V Leiden mutation and of their related family members.
      To our knowledge, the second patient in this study is the first patient reported
      to have cerebral infarctions associated with the combination of the factor V
      Leiden mutation and persistent high titers of serum beta(2)-glycoprotein I
      antibodies.

PMID- 17005113
TI  - Usefulness of ocular compression during electroencephalography in distinguishing
      breath-holding spells and syncope from epileptic seizures.
AB  - Episodes of syncope or breath-holding spells are often misdiagnosed as epileptic
      events. The purpose of this study was to assess the usefulness of an
      electroencephalogram (EEG) with ocular compression to distinguish breath-holding
      spells and syncope from epileptic seizures. A retrospective analysis was
      performed on the EEG records of all children on whom ocular compression was
      performed from 2000 to 2003. Data from 116 patients with a clinical diagnosis
      consistent with either syncope or breath-holding spells were compared with a
      group of 46 patients with epilepsy. The RR interval during ocular compression was
      significantly higher in syncope patients compared with patients with epilepsy (P
      < .005). Using 2 seconds of asystole as the cutoff, the sensitivity of ocular
      compression was 26%, with 100% specificity. The change in RR interval from
      baseline to ocular compression also distinguished patients with breath-holding
      spells and syncope from patients with epilepsy. Even a small increase of 0.5
      seconds in the RR interval demonstrated a sensitivity of 46%, with a specificity
      of 98%. Ocular compression performed during an EEG is useful in distinguishing
      patients with breath-holding spells and syncope from those with epileptic
      seizures. A requirement of a 2-second period of asystole with ocular compression
      excludes many patients. Our data indicate that an RR interval increase of 0.5
      seconds over baseline identifies additional patients with increased vagal tone.
      Prompt and accurate diagnosis of the etiology of loss of consciousness might
      preclude the need for further extensive and expensive evaluation and reduce
      patient and parental distress.

PMID- 17005114
TI  - Childhood encephalitis in Crete, Greece.
AB  - This study included all 18 cases of children hospitalized for encephalitis in the
      referral university hospital of Heraklion, Crete, Greece, during the 5-year
      period from 2000 to 2004. Encephalitis was attributed to viral infection
      (echovirus, herpes simplex virus 1, varicella-zoster virus, cytomegalovirus, and
      influenza A) in eight children and to bacteria (Mycoplasma pneumoniae, group A
      beta-hemolytic streptococcus, and Rickettsia typhi) in a further five cases.
      Multiple hyperintense brain lesions on magnetic resonance imaging (MRI) were
      associated with a severe clinical presentation but not with a guarded long-term
      outcome. Five children still presented with mild to moderate sequelae after 1.5
      to 5.3 (median 4.0) years. Our findings confirm the elimination of measles,
      mumps, and rubella-associated encephalitis in the postvaccine era. MRI appeared
      to be of great diagnostic value. Although no fatalities were observed, deficits
      did persist in several patients.

PMID- 17005115
TI  - Giant axonal neuropathy: diffusion-weighted imaging features of the brain.
AB  - Giant axonal neuropathy is a rare autosomal recessive childhood disorder
      characterized by a peripheral neuropathy and features of central nervous system
      involvement. Magnetic resonance imaging (MRI) of an 11-year-old boy with giant
      axonal neuropathy revealed high signal intensity in the white matter of the
      cerebrum and cerebellum on T(2)-weighted imaging. An apparent diffusion
      coefficient map revealed increased apparent diffusion coefficient values in the
      periventricular, deep, and cerebellar white matter, basal ganglia, and thalamus.
      Increased apparent diffusion coefficient values in distinct locations suggest
      increased mobility of water molecules in the brain of a patient with giant axonal
      neuropathy. This finding could indicate a myelin disorder such as demyelination.
      Diffusion-weighted imaging should be performed to reveal apparent diffusion
      coefficient changes and determine brain involvement in patients with giant axonal
      neuropathy.

PMID- 17005117
TI  - Fetal testosterone and sex differences in typical social development and in
      autism.
AB  - Experiments in animals leave no doubt that androgens, including testosterone,
      produced by the testes in fetal and/or neonatal life act on the brain to induce
      sex differences in neural structure and function. In human beings, there is
      evidence supporting a female superiority in the ability to read nonverbal
      signals, specific language-related skills, and theory of mind. Even more striking
      than the sex differences seen in the typical population is the elevated
      occurrence of social and communicative difficulties in human males. One such
      condition, autism, occurs four times more frequently in boys than in girls.
      Recently, a novel theory known as the "extreme male brain" has been proposed. It
      suggests that the behaviors seen in autism are an exaggeration of typical sex
      differences and that exposure to high levels of prenatal testosterone might be a
      risk factor. In this article, we argue that prenatal and neonatal testosterone
      exposures are strong candidates for having a causal role in sexual dimorphism in
      human behavior, including social development, and as risk factors for conditions
      characterized by social impairments, particularly autism spectrum conditions.

PMID- 17005118
TI  - Effects of thermodynamic nonideality in ligand binding studies.
AB  - Effects of thermodynamic nonideality are considered in relation to the
      quantitative characterization of the interaction between a small ligand. S, and a
      macromolecular acceptor. A, by two types of experimental procedure. The first
      involves determination of the concentration of ligand in dialysis equilibrium
      with the acceptor/ligand mixture, and the second, measurement of the
      concentration of unbound ligand in the reaction mixture by ultrafiltration or the
      rate of dialysis method. For each situation explicit expressions are formulated
      for the appropriate binding function with allowance for composition-dependent
      nonideality effects expressed in terms of molar volume, charge-charge interaction
      and covolume contributions. The magnitudes of these effects are explored with the
      aid of experimental studies on the binding of tryptophan and of methyl orange to
      bovine serum albumin. It is concluded for experiments conducted utilizing either
      equilibrium dialysis or frontal gel chromatography that, provided a correction is
      made for any Donnan redistribution of ligand, theoretically predicted acceptor
      concentration dependence is likely to be negligible and that use of the
      conventional binding equation written for an ideal system is appropriate to the
      analysis of the results. Use of ultrafiltration or the rate of dialysis method
      requires examination of the assumption that the activity coefficient ratio
      y(A)y(s)/y(AS) for the reaction mixture approximates unity; but again reassurance
      is provided that nonideality manifested as a dependence of the binding function
      on acceptor concentration is unlikely to be significant.

PMID- 17005119
TI  - The evaluation of an average nucleotide composition from melting curves.
AB  - A new formula has been derived for the calculation of the average G + C content -
      X of DNAs from different origins using thermal melting data. As compared to
      existing formulas the new method gives highly accurate results, although being
      much easier to use than similar equations.

PMID- 17005120
TI  - Light-scattering studies of the alpha-ketoglutarate dehydrogenase complex from
      escherichia coli. I. Characterization of the self-association of the complex.
AB  - The self-association of Escherichia coli alpha-ketoglutarate dehydrogenase
      complex (KGDC) purified by a column Chromatographic technique, was characterized
      by light-scattering photometry. The complex adopts a solution conformation
      somewhat larger than that observed in the electron microscope. The evidence
      suggests a nonideal indefinite self-association model for KGDC in KCl, phosphate
      buffer. The KGDC monomer has a molecular charge of about -3 x 10(2) at neutral
      pH. The self-association is promoted by increasing KCl concentrations, pH (in the
      range from 6.3 to 7.4) and temperature (from 20 to 30 degrees C). The effects of
      pH changes suggest a release of protons during the self-association and a minor
      'preferential' interaction of phosphate ions. For the association of one monomer
      to the aggregate at neutral pH and 25 degrees C. DeltaG degrees = -7.8 kcal mol(
      1). DeltaH degrees = 24 kcal mol(-1) and DeltaS degrees = 1.1 x 10(2) cal mol(-1)
      K(-1). These data indicate that hydrophobic interactions drive the association.
      Thermodynamically, the self-association of KGDC is a complex phenomenon and may
      serve to stabilize the enzyme complex in solution.

PMID- 17005121
TI  - Reaction field effects on proton transfer in the active site of actinidin.
AB  - The feasibility of the inclusion of reaction field effects in accurate ab initio
      self-consistent field-molecular orbital calculations was studied in the case of
      proton transfer in the active site of actinidin. The effects of the
      polarizability of the environment were included, using the direct reaction field
      model, which treats the environment as a set of interacting polarizable atoms. Up
      to 1000 of these atoms could be treated but about 300 were sufficient. The full
      geometry of the active site and the environment was taken into account. The
      stabilization of the ion pair was calculated to be 3.5 kcal. but this value may
      be 10 kcal depending on the geometry used. The effect of the static field from
      the long alpha-helix present in the enzyme was also studied. Dispersion effects
      are shown to be unimportant. The orientational polarizability of side chains and
      water molecules was not included.

PMID- 17005122
TI  - Synchrotron excitation of DNA fluorescence. Decay time evidence for excimer
      emission at room temperature.
AB  - The first lifetime measurements of DNA fluorescence are reported. Natural and
      synthetic DNA have been excited by 1.76 ns pulses of synchrotron ultraviolet
      radiation (270 nm) and the time profile of the fluorescence has been measured by
      synchronous single-photon counting. A post-pulse exponentially decaying emission
      has been observed with a lifetime of 2.9 +/- 0.4 ns for calf thymus DNA and 3.0
      +/- 0.3 ns for poly(dA-T); this is most likely an excimer fluorescence.

PMID- 17005123
TI  - A new measure of cooperativity in protein-ligand binding.
AB  - An allosteric binding system consisting of a single ligand and a nondissociating
      macromolecule having multiple binding sites can be represented by a binding
      polynomial. Various properties of the binding process can be obtained by
      analyzing the coefficients of the binding polynomial and such functions as the
      binding curve and the Hill plot. The Hill plot has an asymptote of unit slope at
      each end and the departure of the slope from unity at any point can be used to
      measure the effective interaction free energy at that point. Of particular
      interest in detecting and measuring cooperativity are extrema of the Hill slope
      and its value at the half-saturation point. If the binding polynomial is
      symmetric, then there is an extremum of the Hill slope at the half-saturation
      point. This value, the Hill coefficient, is a convenient measure of
      cooperativity. The purpose of this paper is to express the Hill coefficient for
      symmetric binding polynomials in terms of the roots of the polynomial and to give
      an interpretation of cooperativity in terms of the geometric pattern of the roots
      in the complex plane. This interpretation is then applied to the binding
      polynomials for the MWC (Monod-Wyman-Changeux) and KNF (Koshland-Nemethy-Filmer)
      models.

PMID- 17005124
TI  - Kinetic and thermodynamic parameters for oxygen binding to the allosteric states
      of Panulirus interruptus hemocyanin.
AB  - The temperature dependence of the oxygen binding equilibria and kinetics of
      Panulirus interruptus hemocyanin has been analyzed within the context of the two
      state allosteric model. Oxygenation of the T-state is characterized by a more
      negative value of DeltaH than that of the R-state; therefore, cooperative effects
      in oxygen binding to P. interruptus hemocyanin are thermodynamically governed by
      favorable entropy changes. The allosteric transition in the unliganded derivative
      shows an enthalpy-entropy compensation effect. The activation enthalpies for
      oxygenation and deoxygenation of the T-state are larger than those for the R
      state, while the activation entropies are favorable for the T-state and
      unfavorable for the R-state. Thus, the activation free energies for oxygen
      binding to the T- and R-states are similar, while for the deoxygenation reaction
      DeltaG++ is smaller for the T-state. The analysis reported confirms the
      applicability of the Monod-Wyman-Changeux two-state allosteric model to P.
      interruptus hemocyanin and yields a complete thermodynamic characterization of
      oxygen binding under both equilibrium and dynamic regimes.

PMID- 17005125
TI  - A spectrofluorometric study of the environment of tryptophans in
      bacteriorhodopsin.
AB  - The emission spectrum of intact purple membranes of Halobacterium halobium has a
      very short wavelength position (the main maximum at 314 nm) and can be fitted by
      two spectral components, one of which (component A) corresponds to the
      fluorescence of buried tryptophan residues located in a highly hydrophobic rigid
      environment (like the single tryptophan residue in azurin), the other (component
      I) being due to the emission of buried tryptophan residues located in a rather
      polar environment. Treatment of bacteriorhodopsin by NaBH4, fragmentation of the
      membranes and thermal formation of vesicles result in a decrease in the
      contribution of component A, an increase in that of component I and the
      appearance of spectral components corresponding to the emission of surface
      tryptophan residues. Temperature induces at least two distinct changes of the
      fluorescence parameters of the protein: one change occurs from 45 to 65 degrees
      C. the other from 65 to 90 degrees C. The spectral changes correlate with the
      peaks of heat sorption caused by thermal transitions in the purple membrane
      structure and conformational changes in the protein structure. Alkaline
      denaturation of bacteriorhodopsin registered by tryptophan fluorescence begins at
      pH > 11.0.

PMID- 17005126
TI  - Repulsive stabilization in black lipid membranes. A hydrodynamic model.
AB  - A linear stability analysis is performed for a black lipid membrane. The
      hydrodynamic model consists of a viscous hydrocarbon film sandwiched between two
      aqueous phases. Attractive forces (van der Waals and electrical) and repulsive
      forces (steric) are expressed as body forces in the equations of fluid motion in
      the three phases. The steric repulsion due to overlap of the hydrocarbon chains
      of the lipids at small film thicknesses is described via an exponentially
      decaying interaction potential. The dispersion equation displays two modes of
      vibrations: the bending mode with the two Film surfaces transversely in phase,
      and the squeezing mode with the two surfaces 180 degrees out of phase. For
      symmetrical films, these two modes are uncoupled, and the squeezing mode (with
      thickness variations) is stabilized by the repulsive interactions. For
      nonsymmetrical films (different surface tensions, surface charges, etc.). these
      two modes are coupled and the asymmetry induces a shift of the marginal stability
      curve to shorter wavelengths.

PMID- 17005127
TI  - Experimental study of synchronization phenomena under periodic light irradiation
      of a nonlinear chemical system.
AB  - A photosensitive chemical oscillating reaction, i.e., the Briggs-Rauscher (B.R.)
      reaction, exhibiting a wealth of nonlinear behavior, when performed in a
      continuous-flow stirred-tank reactor, and subjected to periodic light
      irradiation, is studied as an experimental example of entrainment phenomena
      observable in biological systems. The adaptation patterns under periodic light
      irradiation are elucidated by means of the response of the system to continuous
      and single-pulse light irradiation. It is shown that self-oscillating states,
      excitable steady states and bistable systems can exhibit the same types of
      synchronization patterns when submitted to periodic external forces with
      appropriate amplitude and time scale conditions.

PMID- 17005128
TI  - Transport properties of rigid, symmetrical oligomeric structures composed of
      prolate, ellipsoidal subunits.
AB  - We have calculated translational and rotational diffusion coefficients and
      intrinsic viscosities of oligomeric structures composed of n identical subunits
      having a prolate ellipsoidal shape with axial ratio p. Results are presented for
      p = 1-6 for a variety of structures with n = 1-6. We compare our results with
      those obtained by a different modeling procedure, proposed by other workers, in
      which the monomeric subunit is represented as a string of touching, colinear
      spheres. If n and an estimate of p are known, the structure of the oligomer can
      be. in most cases, unambiguously determined by comparison of the experimental
      oligomer-to-monomer ratios of a given property with the numerical results of this
      work. As examples of the applicability of our results, we examine the
      relationship between structure and properties for neurophysin. bovine serum
      albumin, hemoglobin and phycocyanin.

PMID- 17005129
TI  - Dielectric behavior of polyelectrolytes. III. The role of counterion
      interactions.
AB  - The role of the Coulomb forces between the counterions on the surface of
      polyelectrolytes on the dielectric response is analyzed. An estimate of the
      maximum dielectric increment (as a function of the number of counterions) is
      found as a function of the molecular length. The minimum-energy configuration of
      the counterions on a cylinder is found to be a double helix, suggesting the
      fundamental importance of electrostatic interactions in determining structure.
      Solutions of the dynamical equations for a few counterions indicate that a single
      mode dominates the relaxation which is enhanced by the inter-ion repulsions. A
      lower bound is found for this mode based on analysis of the system response for
      short lengths. Sum rules for the rates and amplitudes of the dipolar correlation
      function are derived and lead to an upper bound for the rate of the dominant
      mode. These bounds approach one another for the parameters characteristic of
      restriction fragments of DNA. This permits a prediction of the magnitude and time
      scale of the dielectric response.

PMID- 17005130
TI  - Time-dependent rotational rates of excited fluorophores. A linkage between
      fluorescence depolarization and solvent relaxation.
AB  - It is generally assumed that the rotational diffusion coefficients of
      fluorophores are independent of time subsequent to excitation, and that the
      rotational diffusion coefficients of the ground and the excited states are the
      same. We now describe a linkage between the extent of solvent relaxation and the
      rate of fluorescence depolarization. Specifically, if a fluorophore displays time
      dependent solvent relaxation it may also show a time-dependent decrease in its
      rotational rate. A decreased rate of rotation could result from the increased
      interaction with polar solvent molecules which occurs as a result of solvent
      relaxation. The decays of anisotropy predicted from our model closely mimic those
      often observed for fluorophores which are bound to macromolecules. For example,
      the decays are more complex than a single exponential, and the time-resolved
      anisotropy can display a limiting value which does not decay to zero. The effect
      of solvent relaxation upon the rates of rotational diffusion is expected to be
      most dramatic for solvent-sensitive fluorophores in a viscous environment. These
      conditions are frequently encountered for fluorophore-macromolecule complexes.
      Consideration of the linkage between solvent relaxation and rotational diffusion
      leads to two unusual predictions. First even spherical fluorophores in an
      isotropic environment could display multi- or nonexponential decays of
      fluorescence anisotropy. Secondly, for the special case in which the fluorophore
      dipole moment decreases upon excitation, the theory predicts that the anisotropy
      decay rate may increase with time subsequent to pulsed excitation. The
      predictions of this theory are consistent with published data on the effects of
      red-edge excitation upon the apparent rotational rates of fluorophores in polar
      solvents.

PMID- 17005131
TI  - A new theoretical approach to the investigation of the symmetry of protein
      oligomers with bifunctional reagents.
AB  - The use of bifunctional reagents to form cross-links between subunits in protein
      oligomers and subsequent disruption of noncovalent interactions with SDS allows
      comment upon the number of subunits and the symmetry in the original assembly. In
      existing treatments the number of equations needed to describe theoretically the
      proportions of all the cross-linked species that can be formed as a function of
      time in this way makes the analysis of the system unmanageable for proteins with
      more than four subunits. A method is presented that allows the required equations
      for any oligomer to be formulated as an algorithm suitable for solution by
      computer. Its application is illustrated with reference to experimental results
      obtained with two protein hexamers, Jasus hemocyanin and alpha-urease from jack
      bean.

PMID- 17005133
TI  - The influence of temperature on the flocculation rate of renneted casein
      micelles.
AB  - The flocculation rate constant of completely renneted casein micelles in milk
      ultrafiltrate was measured by Rayleigh light scattering between 20 and 35 degrees
      C. In this temperature range an apparent energy of activation of 103 kJ mol (+/
      11 kJ mol : n = 50) was measured. At 15 degrees C clotting was not longer
      perceptible. The activation of the flocculation between 20 and 35 degrees C is
      explained not so much by the height of the energy barrier separating the clotting
      micelles, as by the very negative temperature coefficient of that barrier. In
      line with this conclusion it is suggested that renneted micelles adhere through
      hydrophobic bonding. The flocculation rate constant of renneted casein micelles
      is independent of micelle size at the four temperature levels studied.

PMID- 17005132
TI  - Interaction of the cationic form of amphiphilic drugs with phosphatidylcholine
      model membranes. Competition with lanthanide ions.
AB  - Model membranes (liposomes) of egg yolk phosphatidylcholine were exposed to the
      charged (cationic) form of amphiphilic drugs (procaine, tetracaine, metroprolol,
      alprenolol and propranolol). Drug analysis by ultraviolet light absorption of the
      bulk solution after centrifugation separation was used to determine the amount of
      drug bound to the membranes. Microelectrophoresis was employed to measure the
      change in the zeta-potential after drug adsorption. Binding constants were
      derived by simulating the experimental curves with a theoretical model which
      considers the electrostatic effects (Gouy-Chapman theory). Analogous experiments
      were carried out for the adsorption of Eu3+. Metal analysis was made by three
      different methods. Good agreement between the centrifugation and electrophoresis
      experiments was obtained for reasonable positions of the plane of shear relative
      to the positional plane of the bound ions. Displacement of Eu3+ from vesicles
      upon addition of drug cations was followed by 31P-NMR. The competition
      experiments were numerically simulated. The Eu3+ binding was assumed to obey a
      mass action type equilibrium, whereas the drug binding was described by a Henry's
      law partition. The binding constants for the drugs in the competition experiments
      followed the same order as in the absence of Eu3+. However, the numerical values
      had to be reduced. The effect of anions was studied.

PMID- 17005134
TI  - pH modulation of transient state kinetics of enzymes. II. Transient state
      kinetics of plant cell wall acid phosphatase.
AB  - The pre-steady-state kinetics of plant cell wall acid phosphatase has been
      investigated at different pH values. The approach of the steady stale lasts about
      1 or 2 s and may be fitted with two exponential terms. For certain pH values the
      approach to the steady state exhibits damped oscillations. Plotting the sum and
      the product of the two time constants of these exponentials as a function of
      substrate concentration yields two straight lines. From the slopes and intercepts
      of these lines one may determine the values of rate and ionization constants
      involved in the reaction scheme. The results obtained are consistent with the
      view that the binding of the substrate to the enzyme does not induce a 'slow'
      conformation change of the enzyme. The enzyme reacts with its substrate while
      being mostly in its ionized form. Release of p-nitrophenol is also favoured by
      this ionized form of the enzyme. However, the hydrolysis of the phosphoryl-enzyme
      complex mostly occurs from the protonated form of the enzyme. The ionization
      constants of the free enzyme and of the various enzyme-ligand complexes are very
      similar.

PMID- 17005135
TI  - Models for the analytical ultracentrifuge behavior of Helix pomatia alpha
      hemocyanin. I. Experimental testing of previous models.
AB  - The 'microheterogeneity model' (R.J. Siezen and R. van Driel, Biochim. Biophys.
      Acta 295 (1973) 131) and the 'incompetent whole molecule model' (G. Kegeles,
      Arch. Biochem. Biophys. 180 (1977) 530) for the dissociation of Helix pomatia
      alpha-hemocyanin whole molecules to half molecules were tested experimentally,
      using ultracentrifugation and stopped-flow dilution analysis. Results of
      differential sedimentation experiments followed by stopped flow analysis of
      separated fractions of 60 S and 100 S molecules were not entirely as predicted by
      the incompetent model, the agreement depending on the pH and ionic strength of
      analysis. A considerable amount of stopped-flow dilution response could be
      attributed to material sedimenting between 60 and 100 S. This material appears to
      be the main equilibrating fraction, and its amount is considerably larger than
      that predicted by the microheterogeneity model. Increased hydrostatic pressure
      was found to enhance this fraction, whereas fixation or low ionic strength
      reduced or eliminated this fraction. Nonequilibrium components of 30, 50 and 80 S
      were detected and partially purified by differential sedimentation.

PMID- 17005136
TI  - Models for the analytical ultracentrifuge behavior of Helix pomatia alpha
      hemocyanin. II. Simulations of reacting microheterogeneous hemocyanin.
AB  - Simulations for the moving-boundary ultracentrifuge behavior of Helix pomatia
      alpha-hemocyanin have been developed, based on modification of published models.
      In the present treatment, it has been assumed that the protein system is
      extensively microheterogeneous, with respect to its whole-half molecule
      reactivity. It has also been assumed that all such association and dissociation
      reactions can proceed to equilibrium in a time appreciably shorter than that
      which would be required to separate nonreacting half molecules from nonreacting
      whole molecules. Predictions based on this model agree well with reported
      experimental findings of nonequilibration of fractionated material, apparent
      independence of whole-to-half molecule concentration ratios on total
      concentration in sedimentation experiments, and stopped-flow dilution reactivity
      over a wide range of sedimentation coefficients.

PMID- 17005137
TI  - Absorption and magnetic circular dichroism of chlorophyll a and b dimers.
AB  - The dimerization of chlorophyll a to the so-called special pair, in which the two
      monomers are linked together by two nucleophilic molecules (alcohol or water),
      leads to shifts and splittings of the absorption and magnetic circular dichroism
      (MCD) spectral bands. The changes in the Q-band region are described starting
      from a model proposed previously (L.L. Shipman. J.R. Morris and J.J. Katz. J.
      Phys. Chem. 80 (1976) 877). and which we extended to include the MCD. The
      parameters alpha(x) and alpha(y), containing the exciton and environmental
      parameters (L.L. Shipman. J.R. Norris and J.J. Katz, J. Phys. Chem. 80 (1976)
      877) and the relative orientation of the monomers in the dimer, determine the
      spectral features. Spectral simulation leads to the conclusion that in the
      special pair alpha(x) and alpha(y), are in the region of 0.6-0.8 and that the
      dimer has C2 symmetry. The model was also applied to the case of the pure dimer
      of chlorophyll b where the monomers are bound together directly. With similar
      values for alpha(x) and alpha(y) the spectra could be reconstructed assuming
      almost parallel monomers in the dimer, the equilibrium constant for the
      association 2M <==> M2 was determined as 0.8(+/-0.2) x 10(6) mol(-1)/I. The
      present choice of compounds was based merely on practical reasons. The model may
      be applied equally well to other similar cases.

PMID- 17005138
TI  - Absorption, circular dichroism, magnetic circular dichroism and emission study of
      rat kidney Cd,Cu-metallothionein.
AB  - Absorption, circular dichroism (CD), magnetic circular dichroism (MCD) and
      emission spectra of rat liver and rat kidney cadmium-, zinc- and copper
      containing metallothioneins (MT) are reported. The absorption, CD and MCD data of
      native rat kidney Cd,Cu-MT protein closely resemble data recorded for the rat
      liver Cd,Zn-MT. This suggests that the major features in all three spectra of the
      native Cd,Cu-MT are dominated by cadmium-related bands. The CD spectrum of the
      Cd,Cu-MT recorded at pH 2.7 has the same band envelope that is observed for a
      Cd,Cu-MT formed in vitro by titration of Cd,Zn-MT with Cu(I), suggesting that the
      copper occupies the zinc sites in Cd,Cu-MT formed both in vivo and, at low molar
      ratios, in vitro. Remetallalion of the metallothionein from low pH in the
      presence of both copper and cadmium results in considerably less cadmium bound to
      the protein than was present in the native sample. It is suggested that this is
      due to the effect of the distribution of the copper amongst all available binding
      sites, thus inhibiting cluster formation by the cadmium. Emission spectra are
      reported for the first time for a cadmium- and copper-containing metallothionein.
      An emission band at 610 nm is shown to be a sensitive indicator of Cu(I) binding
      to metallothionein. Both the native Cd,Cu-MT and a Cd,Cu-MT formed in vitro
      exhibit an excitation spectrum with a band in the copper-thiolate charge-transfer
      region.

PMID- 17005139
TI  - Interactions between ions and polyelectrolytes. A note on determination of ionic
      activities, with reference to a modified poisson-boltzmann treatment.
AB  - We compare the numerous available data on ionic activities, in the presence of
      polyelectrolytes, with evaluation of these quantities from a modified Poisson
      Boltzmann equation in the framework of a cell model. This treatment gives an
      excellent description of the mean activity for various ions. The activity of
      counterions is well-predicted, that of co-ions is generally overestimated.

PMID- 17005140
TI  - Torsional rearrangements of aryl-substituted anthracenes measured by phase
      fluorometry.
AB  - We examined the fluorescence phase angle spectra of aryl-substituted anthracenes
      in viscous solvents. These phase angles reflect the wavelength-dependent
      lifetimes displayed by the fluorophores. At intermediate viscosities the phase
      angles increased and decreased in accordance with the valleys and peaks of the
      structured emission spectra. At lower and higher temperatures the phase angles
      were independent of emission wavelength, which is equivalent to decay times which
      are independent of emission wavelength. We attribute the wavelength-dependent
      phase angles to rotation of the unsaturaled side chains towards a conformation
      more coplanar with the anthracene ring. By comparative studies with 9,10-di(alpha
      naphthylanthracene), 9,10-di-phenylanthracene, and 9-vinylanthracene we showed
      that lower temperatures are required to inhibit rotation of the smaller phenyl
      and vinyl substitutents. Since these excited-state rearrangements are sensitive
      to the motional freedom allowed by the surrounding solvent, we suggest that this
      phenomenon may serve as a probe of volume fluctuations in macromolecules.

PMID- 17005141
TI  - The dielectric permittivity spectrum of aqueous colloidal phospholipid solutions
      between 1 kHz and 60 GHz.
AB  - The dielectric permittivity spectrum between 1 kHz and 60 GHz of aqueous
      colloidal solutions of predominantly zwitterionic phospholipids is presented from
      results of previous and recent measurements. It shows three dispersion/loss
      regions around 22 GHz. 80 MHz and below 40 MHz (30 degrees C) which are
      attributed to rotational diffusion of the water molecules and of the zwitterionic
      phosphorylcholine groups, and to limited translational diffusion of ionic lipid
      molecules and/or its counterions. respectively. Merely a few mole percent of
      ionic lipids cause comparatively large dielectric dispersion. Ignoring the fact
      that such impurities may be present in zwitterionic phospholipid compounds, which
      have not been especially purified, this has led to misinterpretation of the
      dielectric spectrum in the past. An approximate quantitative description of the
      measured spectra is given for vesicle solutions with only very small additional
      low-molecular-weight salt content. It reproduces the sensitive dependence of the
      ionic lipid-induced dielectric dispersion (step height and frequency) on various
      parameters: phospholipid vesicle size. ionic lipid content, as well as the self
      diffusion coefficient of the ionic lipid molecules and of its counterions, moving
      within the phospholipid bilayers or on their surface, respectively.

PMID- 17005142
TI  - The interactions between nucleic acids and polyamines. III. Microscopic
      protonation constants of spermidine.
AB  - Changes in the NMR chemical shifts of protons adjacent to the nitrogen atoms of
      Spermidine which are undergoing protonation have been measured by two-dimensional
      heteronuclear coupled NMR. Data thus obtained measure the dependence of the state
      of protonation of individual nitrogens on the pH, and permit calculation of the
      microprotonation constants of Spermidine and the concentrations of all of the
      variously protonated Spermidine species present at any pH.

PMID- 17005143
TI  - Thermodynamical model of indefinite mixed association of two components and NMR
      data analysis for caffeine-AMP interaction.
AB  - This paper describes the model used to estimate the parameters of caffeine-AMP
      interactions from corresponding 1H-NMR measurements and some methods of data
      analysis by which the applicability of the model has been checked. The model of
      mixed association is applicable to a mixture of any two substances A and C which
      exhibit indefinite aggregates in both self-association and mixed association. In
      aggregates, only nearest neighbour interaction is assumed. The model is described
      by three equilibrium constants: Kaa and Kcc (for self-association of A, or C,
      respectively), and Kac (for mixed association).

PMID- 17005144
TI  - Thermodynamical model for insertion and aggregate binding of caffeine to the
      homopolymer poly(riboadenylate) and model choice by data analysis.
AB  - This paper describes the model used to estimate the parameters of caffeine
      poly(riboadenylate) (poly(A)) interactions from corresponding 1H-NMR
      measurements. The model of insertion and aggregate binding describes the non
      cooperative insertion of a molecule C into an interspace between two monomers of
      a homopolymer in competition with aggregate binding. It contains two binding
      constants, K1 for insertion and K2 for the interaction of monomeric A units of
      the polymer with C molecules in bound aggregates, and two cooperativity
      parameters, Kcc for stacking of C molecules within aggregates and tau which is
      thought to be due to conformational adaptation of the polymer to those bound
      aggregates which cover more than one A unit. In contrast to other models, the
      size of a binding site (within the aggregates) is less than one monomeric unit,
      with n denoting the maximum number of C molecules per A unit in bound aggregates.
      The model is developed for general n by means of the method of sequence
      generating functions. For n = 2 and n = 3, the correctness of the model treatment
      was checked by the matrix method. The model is applicable to the binding of
      aggregates to homopolymers, which are flexible enough to fit their structure to
      the aggregates.

PMID- 17005145
TI  - Effect of ligand binding and conformational changes in proteins on oxygen
      quenching and fluorescence depolarization of tryptophan residues.
AB  - The rotational freedom of tryptophan residues in protein-ligand complexes was
      studied by measuring steady-state fluorescence anisotropies under conditions of
      oxygen quenching. There was a decrease in the oxygen bimolecular quenching
      constant upon complexation of trypsin and alpha-chymotrypsin with proteinaceous
      trypsin inhibitors, of lysozyme with N-acetylglucosamine (NAG) and di(N-acetyl-D
      glucosamine) ((NAG)2) and of hexokinase with glucose. Binding of the bisubstrate
      analogue N-phosphonacetyl-L-aspartate (PALA) to aspartate transcarbamylase
      (ATCase) and binding of biotin to avidin resulted in increased oxygen quenching
      constants. The tryptophan of human serum albumin (HSA) in the F state was more
      accessible to oxygen quenching than that in the N state. With the exception of
      ATCase, the presence of subnanosecond motions of the tryptophan residues in all
      the proteins is suggested by the short apparent correlation times for
      fluorescence depolarization and by the low apparent anisotropies obtained by
      extrapolation to a lifetime of zero. Complex formation evidently resulted in more
      rigid structures in the case of trypsin, alpha-chymotrypsin and lysozyme. The
      effects of glucose binding on hexokinase were not significant. Binding of biotin
      to avidin resulted in a shorter correlation time for the tryptophan residues. The
      N --> F transition in HSA resulted in a more rigid environment for the tryptophan
      residue. Overall, these changes in the dynamics of the protein matrix and
      motional freedom of tryptophan residues due to complex formation and subsequent
      conformational changes are in the same direction as those observed by other
      techniques, especially hydrogen exchange. Significantly, the effects of complex
      formation on protein dynamics are variable. Among the limited number of cases we
      examined, the effects of complex formation were to increase, decrease or leave
      unchanged the apparent dynamics of the protein matrix.

PMID- 17005146
TI  - Intrinsic fluorescence of a non-myelin apoproteolipid and evidence for the
      existence of conformational flexibility.
AB  - An extremely hydrophobic protein (Mr = 16000), which in its native form is only
      soluble in organic solvents and which differs from the myelin proteolipid (Mr =
      24000), was purified to homogeneity. Intrinsic fluorescence studies on this
      apoproteolipid have revealed a large conformational flexibility. In the water
      soluble form the emitting residues appear to be buried in a hydrophobic core
      while in organic solvents they are exposed to the external medium. Structural
      changes depending on the organic solvent are also observed. The emission
      characteristics of reconstituted proteoliposomes may be due to the formation of a
      membrane-linked complex between several proteolipid monomers.

PMID- 17005147
TI  - On the rotational brownian motion of a bacterial idle motor. I. Theory of time
      dependent fluorescence depolarization.
AB  - A rotational diffusion equation and its Green's function for a spheroidal
      particle such as a bacterial body, to which an actively driving but idle motor is
      attached, are presented. As an application of the theory, general expressions for
      the time-dependent fluorescence depolarization caused by such a particle have
      been obtained. Measurement of such depolarizalion should provide a useful tool
      for determination of the rate of revolution of the rotating motor attached to
      cell bodies such as bacteria under various solution conditions, if a fluorescent
      (or phosphorescent) label is attached to the motor shaft.

PMID- 17005148
TI  - Interaction of (dien)Pd(II) with cytidine and cytidine 5'-monophosphate.
      Influence of the phosphate group on the kinetics and mechanism.
AB  - The kinetics and the equilibrium of (dien)PdCl+ interaction with cytidine (C) and
      cytidine 5'-monophosphate (CMP) were studied by spectrophotometry and by stopped
      flow methods. In both cases, the mechanism implies a (dien)Pd(H2O)2+ intermediate
      with a significant contribution of the solvent path at low chloride
      concentrations. With CMP, the rate is affected due to the addition of a
      mechanistic path via an intermediate formed between (dien)Pd(II) and the
      phosphate group of CMP. The kinetic and thermodynamic parameters have been
      determined and reflect the favorable electrostatic interactions due to the
      presence of the phosphate group of CMP. Furthermore, these parameters are in
      agreement with a transient (dien)Pd(II)-phosphate complex of CMP leading to the
      formation of the thermodynamically favored (dien)Pd(II)-N3 complex as final
      product.

PMID- 17005149
TI  - Current-voltage characteristics and self-sustained oscillations in dioleyl
      phosphate-millipore membranes.
AB  - For an artificial membrane prepared by infiltrating dioleyl phosphate (DOPH) into
      pores of a Millipore filter, we propose a theoretical model for explaining
      observed data on electric behavior, such as d.c. current-voltage characteristics
      and self-sustained oscillations of the electric potential. The model consists of
      a simple electric circuit composed of electric resistances and capacitances as
      given functions of internal variables which represent conformational states of
      DOPH molecules and salt concentration inside the pore concerned. The kinetic
      equations for these variables are the same as those presented previously for
      describing a phase transition of DOPH. except for a slight modification taking
      account of effects of salt accumulation inside the pore. The present theory can
      describe well the I-V hysteresis and various features of spike-like oscillations
      with long periods of up to a few hours in the absence of external force and also
      short-period oscillations with periods of the order of 1 s under pressure
      difference.

PMID- 17005150
TI  - Structural properties of barley nucleosomes.
AB  - The structural properties of barley oligonucleosomes are investigated and
      compared to those of rat liver oligomers. Extraction of barley chromatin was
      performed using mild nuclease digestion of isolated nuclei leading to a low ionic
      strength soluble fraction. Oligonucleosomes were fractionated on sucrose
      gradients and characterized for DNA and histone content. Physico-chemical studies
      (sedimentation, circular dichroism and electric birefringence) showed that barley
      oligonucleosomes exhibit properties very close to those of the H1-depleted rat
      liver counterparts. Moreover, in situ, barley linker DNA was more sensitive to
      micrococcal nuclease digestion than that of rat liver. These results suggest that
      barley oligonucleosomes show a less compact structure than their rat liver
      counterparts and appear to be in contradiction with the very condensed
      organization of barley chromatin previously suggested.

PMID- 17005151
TI  - Simulations of frequency-dependent photoacoustic magnitude signals and their
      implications for bacteriorhodopsin photocycle energetics.
AB  - The modulation frequency dependence of photoacoustic signals obtained from
      photoactive samples can provide information on the time-dependent enthalpy
      changes occurring during the light-induced process. The experimental requirements
      for this type of calorimetry, and the interpretation ot the results, are
      critically examined with reference to the light-driven proton pump
      bacteriorhodopsin. For a three-step unbranched model of the bacteriorhodopsin
      photocycle we derive an expression for the photoacoustic magnitude signal as a
      function of frequency. Simulations are performed for various values of the rate
      constants and energetic changes. It is shown that the net heat uptake during a
      low, final step postulated by some workers should be reflected in the
      photoacoustic magnitude frequency spectrum, giving rise to a characteristic
      maximum. However, this effect, which has been observed experimentally, may also
      be produced by a fast, strongly endothermic step occurring earlier. The precise
      chronology of an endothermic transition cannot be resolved unambiguously by
      magnitude measurements alone, although they are free from assumptions regarding
      difficult-to-measure phase relationships. Hence, the published photoacoustic
      observations showing the effect are consistent with a cyclic sequence of events
      in which the bacteriorhodopsin system first undergoes an increase of entropy,
      followed by a decrease on returning to the initial state, as well as the reverse.
      It is argued that the molecular disorder-order sequence is more probable.

PMID- 17005152
TI  - Fatty acid contamination and dielectric relaxation in phospholipid vesicle
      suspensions.
AB  - Aqueous vesicle or micelle suspensions from various synthetic lecithins or
      surfactants - most of them purified by a simple ion-exchange procedure in
      methanol - were investigated, some with ionic admixtures. The dielectric
      permittivity '(nu) between 5 kHz and 100 MHz was determined by different time-and
      frequency-domain methods, with attention given to electrode polarization below 1
      MHz. Pure ether lecithins (used to reduce hydrolysis during preparation) as well
      as ester lecithins showed no dielectric dispersion below 10 MHz (Delta' 3). In
      contrast, even dilute colloidal solutions containing about 1 mol% (with respect
      to solute) ionic amphiphiles normally exhibited large dielectric dispersion (10 <
      Delta' < 700), especially with electrolyte present. This low-frequency dispersion
      is sensitive to vesicle coagulation or fusion. Underlying relaxation mechanisms
      are discussed, and the main relaxation is shown to be the same as for other
      charged colloids. This conclusion suggest a new interpretation of measurements,
      previously reported by other authors, who gave an interpretation in terms of
      correlated zwitterionic head group orientation in multilamellar lecithin
      liposomes. Possible effects from traces of impurities in lipids are discussed.

PMID- 17005153
TI  - Fluorescence decay of 1-methylpyrene in small unilamellar l-alpha
      dimyristoylphosphatidylcholine vesicles. A temperature and concentration
      dependence study.
AB  - The fluorescence decay kinetics of 1-methylpyrene in small unilamellar l-alpha
      dimyristoylphosphatidylcholine vesicles above the phase transition temperature
      has been studied as a function of concentration and temperature. When the 1
      methylpyrene/phospholipid ratio equals 1:2000 no excimer is observed and the
      fluorescence decay is monoexponential. When this ratio is equal to or higher than
      1 200, excimer is observed and the monomer and excimer decays can be adequately
      described by two exponential terms. The deviation of the monomer decays from
      monoexponentiality cannot be described by a model where the diffusion-controlled
      excimer formation is time dependent. The observed decays are compatible with the
      excimer formation scheme which is valid in an isotropic medium. The activation
      energy of excimer formation is found to be 29-9 +/-1.4 kJ mol . The (apparent)
      excimer formation constant and the excimer lifetime at different temperatures
      have been determined. The diffusion coefficient associated with the excimer
      formation process varies between 2 x 10(-10) m(2)/s at 70 degrees C to 4 x 10(
      11) m(2)/s at 25 degrees C.

PMID- 17005154
TI  - Bicyclist injury severities in bicycle-motor vehicle accidents.
AB  - This research explores the factors contributing to the injury severity of
      bicyclists in bicycle-motor vehicle accidents using a multinomial logit model.
      The model predicts the probability of four injury severity outcomes: fatal,
      incapacitating, non-incapacitating, and possible or no injury. The analysis is
      based on police-reported accident data between 1997 and 2002 from North Carolina,
      USA. The results show several factors which more than double the probability of a
      bicyclist suffering a fatal injury in an accident, all other things being kept
      constant. Notably, inclement weather, darkness with no streetlights, a.m. peak
      (06:00 a.m. to 09:59 a.m.), head-on collision, speeding-involved, vehicle speeds
      above 48.3 km/h (30 mph), truck involved, intoxicated driver, bicyclist age 55 or
      over, and intoxicated bicyclist. The largest effect is caused when estimated
      vehicle speed prior to impact is greater than 80.5 km/h (50 mph), where the
      probability of fatal injury increases more than 16-fold. Speed also shows a
      threshold effect at 32.2 km/h (20 mph), which supports the commonly used 30km/h
      speed limit in residential neighborhoods. The results also imply that bicyclist
      fault is more closely correlated with greater bicyclist injury severity than
      driver fault.

PMID- 17005155
TI  - Calpain-resistant fragment(s) of alpha-synuclein regulates the synuclein-cleaving
      activity of 20S proteasome.
AB  - Alpha-synuclein is a pathological component of Parkinson's disease by
      participating in Lewy body formation. Imbalance in protein turnover could result
      in the abnormal protein aggregation responsible for eventual neuronal cell death.
      This in vitro digestion study showed that both m-calpain and 20S proteasome
      preferentially hydrolyzed the N-terminal half of alpha-synuclein, which made the
      hydrophobic NAC and following acidic C-terminal region resistant against the
      proteolyses. Since the acidic C-terminal region contains the PEST segment-a
      protein degradation signal enriched with amino acids of proline (P), glutamate
      (E), serine (S), and threonine (T)-, the PEST segment has not been processed or
      even required for the proteolyses. Alpha-synuclein would be recognized primarily
      by m-calpain since the common substrate was processed by m-calpain five times
      more effectively than 20S proteasome with k(cat)/K(m) of 1.64 x 10(4)M(-1)s(-1)
      and 0.32 x 10(4) M(-1)s(-1), respectively. The N-terminally truncated protease
      resistant C-terminal fragment of alpha-syn61-140 was demonstrated to stimulate
      the 20S proteasome-mediated breakdown of alpha-synuclein and its mutant forms of
      Ala53Thr and Ala30Pro. The stimulation for Ala53Thr, however, was noticeably less
      efficient than those for the other proteins, which might support the previous
      observation of the prolonged intracellular life span of Ala53Thr by 1.5-fold
      compared to that of wild-type form. We have hypothesized that the N-terminally
      truncated C-terminal fragment derived from the abundant alpha-synuclein through
      intracellular proteolyses could be involved in various physiological or
      pathological effects which might be related to the formation of abnormal protein
      aggregation and subsequent neuronal degeneration by influencing the intracellular
      protein turnover or directly participating in the aggregate formation.

PMID- 17005156
TI  - Limited sensitivity of pigment photo-oxidation in isolated thylakoids to singlet
      excited state quenching in photosystem II antenna.
AB  - Light-induced pigment oxidation and its relation to excited state quenching in
      photosystems antennae have been investigated in isolated thylakoids. The results
      indicate that (i) chlorophyll oxidation takes place in two sequential steps. A
      slow initial phase is followed by a steep increase in the bleaching rate when
      more than one quarter of the chromophores are oxidised. (ii) During the initial
      slow phase, the carotenoid pool is bleached with an apparent rate which is about
      three times faster than that found for chlorophyll a and more than six times
      faster than that of chlorophyll b. (iii) Pigment bleaching has been observed both
      in photosystem I and photosystem II, and it has been possible to estimate a
      similar carotenoid bleaching rate in the two photosystems. (iv) The protection
      conferred by singlet state quenchers in the initial slow phase of pigment
      oxidation is modest. Taking into consideration that both the photosystems are
      subjected to the oxidative treatment, a somewhat larger protective effect than
      those estimated for photo-inhibition in thylakoids [S. Santabarbara, F.M.
      Garlaschi, G. Zucchelli, R.C. Jennings, Biochim. Biophys. Acta 1409 (1999) 165
      170] can be computed, although it is less than 50% of the expected level on the
      basis of the observed reciprocity to the number of incident photons. (v) Pigment
      oxidation is associated with the loss of membrane ultra-structure, which is
      interpreted as originating from a decrease in grana stacking. The dynamics of
      loss of membrane ultra-structure parallel the phases observed for chlorophyll
      photo-bleaching.

PMID- 17005157
TI  - Enhancement of YD spin relaxation by the CaMn4 cluster in photosystem II detected
      at room temperature: a new probe for the S-cycle.
AB  - The long-lived, light-induced radical Y(D) of the Tyr161 residue in the D2
      protein of Photosystem II (PSII) is known to magnetically interact with the
      CaMn(4) cluster, situated approximately 30 A away. In this study we report a
      transient step-change increase in Y(D) EPR intensity upon the application of a
      single laser flash to S(1) state-synchronised PSII-enriched membranes from
      spinach. This transient effect was observed at room temperature and high applied
      microwave power (100 mW) in samples containing PpBQ, as well as those containing
      DCMU. The subsequent decay lifetimes were found to differ depending on the
      additive used. We propose that this flash-induced signal increase was caused by
      enhanced spin relaxation of Y(D) by the OEC in the S(2) state, as a consequence
      of the single laser flash turnover. The post-flash decay reflected S(2)-->S(1)
      back-turnover, as confirmed by their correlations with independent measurements
      of S(2) multiline EPR signal and flash-induced variable fluorescence decay
      kinetics under corresponding experimental conditions. This flash-induced effect
      opens up the possibility to study the kinetic behaviour of S-state transitions at
      room temperature using Y(D) as a probe.

PMID- 17005158
TI  - Social anxiety and the shame of psychosis: a study in first episode psychosis.
AB  - Social anxiety disorder (SaD) or social phobia is a co-morbid affective disorder
      in schizophrenia, present in up to one in three individuals. We employ 'social
      rank' theory to predict that one pathway to social anxiety in schizophrenia is
      triggered by the anticipation of a catastrophic loss of social status that the
      stigma of schizophrenia can entail. A group of 79 people with a first episode of
      psychosis were assessed for social anxiety: hypotheses were tested comparing 23
      socially anxious and 56 non-anxious patients on measures of cognitive appraisals
      of shame/stigma of psychosis and perceived social status, controlling for
      depression, psychotic symptoms and general psychopathology. Participants with
      social anxiety experienced greater shame attached to their diagnosis and felt
      that the diagnosis placed them apart from others, i.e., socially marginalised
      them and incurred low social status. We propose a stigma model of social anxiety
      that makes testable predictions about how the shame beliefs may contaminate
      social interaction and thereby exacerbate and maintain social phobia.

PMID- 17005159
TI  - Retrovirus-mediated conditional immortalization and analysis of established cell
      lines of osteoclast precursor cells.
AB  - Osteoclast precursor cells (OPCs) have previously been established from bone
      marrow cells of SV40 temperature-sensitive T antigen-expressing transgenic mice.
      Here, we use retrovirus-mediated gene transfer to conditionally immortalize OPCs
      by expressing temperature-sensitive large T antigen (tsLT) from wild type bone
      marrow cells. The immortalized OPCs proliferated at the permissive temperature of
      33.5 degrees C, but stopped growing at the non-permissive temperature of 39
      degrees C. In the presence of receptor activator of NFkappaB ligand (RANKL), the
      OPCs differentiated into tartrate-resistant acid phosphatase (TRAP)-positive
      cells and formed multinucleate osteoclasts at 33.5 degrees C. From these OPCs, we
      cloned two types of cell lines. Both differentiated into TRAP-positive cells, but
      one formed multinucleate osteoclasts while the other remained unfused in the
      presence of RANKL. These results indicate that the established cell lines are
      useful for analyzing mechanisms of differentiation, particularly multinucleate
      osteoclast formation. Retrovirus-mediated conditional immortalization should be a
      useful method to immortalize OPCs from primary bone marrow cells.

PMID- 17005160
TI  - Elevated K-ras activity with cholestyramine and lovastatin, but not konjac mannan
      or niacin in lung--importance of mouse strain.
AB  - Our previous work established that hypocholesterolemic agents altered K-ras
      intracellular localization in lung. Here, we examined K-ras activity to define
      further its potential importance in lung carcinogenesis. K-ras activity in lungs
      from male A/J, Swiss and C57BL/6 mice was examined. For 3 weeks, mice consumed
      either 2 or 4% cholestyramine (CS), 1% niacin, 5% konjac mannan (KM), or were
      injected with lovastatin 25mg/kg three or five times weekly (Lov-3X and Lov-5X).
      A pair-fed (PF) group was fed the same quantity of diet consumed by the Lov-5X
      mice to control for lower body weights in Lov-5X mice. After 3 weeks, serum
      cholesterol was assayed with a commercial kit. Activated K-ras protein from lung
      was affinity precipitated with a Raf-1 ras binding domain-glutathione-S
      transferase fusion protein bound to glutathione-agarose beads, followed by
      Western blotting, K-ras antibody treatment, and chemiluminescent detection. Only
      KM reduced serum cholesterol (in two of three mouse strains). In C56BL/6 mice
      treated with Lov-3X, lung K-ras activity increased 1.8-fold versus control
      (p=0.009). In normal lung with wild-type K-ras, this would be expected to be
      associated with maintenance of differentiation. In A/J mice fed 4% CS, K-ras
      activity increased 2.1-fold (p=0.02), which might be responsible for the reported
      enhancement of carcinogenesis in carcinogen-treated rats fed CS. KM feeding and
      PF treatment had no significant effects on K-ras activity. These data are
      consistent with the concept that K-ras in lung has an oncogenic function when
      mutated, but may act as a tumor suppressor when wild-type.

PMID- 17005161
TI  - "Did you see him in the newspaper?" Electrophysiological correlates of context
      and valence in face processing.
AB  - Face recognition emerges from an interaction between bottom-up and top-down
      processing. Specifically, it relies on complex associations between the visual
      representation of a given face and previously stored knowledge about that face
      (e.g. biographical details). In the present experiment, the time-course of the
      interaction between bottom-up and top-down processing was investigated using
      event-related potentials (ERPs) and manipulating realistic, ecological contextual
      information. In the study phase, half of the faces (context faces) were framed in
      a newspaper page entitled with an action committed by the person depicted; these
      actions could have a positive or a negative value, so in this way emotional
      valence could be manipulated. The other half was presented on a neutral
      background (no-context faces). In the test phase, previously presented faces and
      new ones were presented on neutral backgrounds and an old/new discrimination was
      requested. The N170 component was modulated by both context (presence/absence at
      encoding) and valence (positive/negative). A reduction in amplitude was found for
      context faces as opposed to no-context faces. The same pattern was observed for
      negative faces compared to positive ones. Moreover, later activations associated
      with context and valence were differentially distributed over the scalp: context
      effects were prominent in left frontal areas, traditionally linked to person
      specific information retrieval, whereas valence effects were broadly distributed
      over the scalp. In relation to recent neuroimaging findings on the neural basis
      of top-down modulations, present findings indicate that the information flow from
      higher-order areas might have modulated the N170 component and mediated the
      retrieval of semantic information pertaining to the study episode.

PMID- 17005162
TI  - c-Fos immunoreactivity in selected brain regions of rats after heat exposure and
      pyrogen administration.
AB  - We determined c-Fos immunoreactivity (Fos-IR) in selected hypothalamic nuclei,
      the organum vasculosum of the laminae terminals (OVLT) and somatosensory cortex
      of rats after hyperthermia induced by exogenous heat exposure, Gram-negative or
      Gram-positive pyrogen administration. The magnitude of Fos-IR was similar in
      thermoregulatory hypothalamic nuclei of rats after heat exposure or
      lipopolysaccharide (LPS) injection, despite the different origins of the
      hyperthermias. Heat-induced hyperthermia was associated with increased Fos-IR in
      the somatosensory cortex. LPS, but not heat exposure or injection of killed
      Staphylococcus aureus cells activated OVLT neurons. The OVLT may thus not be a
      port of entry for humoral mediators of Gram-positive bacterial fevers.

PMID- 17005163
TI  - Peripheral injection of CCK-8S induces Fos expression in the dorsomedial
      hypothalamic nucleus in rats.
AB  - Peripheral cholecystokinin (CCK) plays a physiological role in the regulation of
      food intake. The dorsomedial hypothalamic nucleus (DMH) has been implicated in
      the brain regulation of food intake and satiety. The aim of this study was to
      determine if peripherally administered CCK affects neuronal activity in the DMH,
      as assessed by Fos expression. Density of Fos-positive neurons was determined in
      the DMH, paraventricular nucleus of the hypothalamus (PVN), arcuate nucleus of
      the hypothalamus (ARC) and ventromedial hypothalamic nucleus (VMH) in non-fasted
      Sprague-Dawley rats in response to intraperitoneally (ip) injection of CCK-8S (2
      microg/kg, n=6) or vehicle (0.15 M NaCl; n=6). CCK-8S increased Fos
      immunoreactivity in the DMH (mean+/-SEM; cells/section: 108+/-10 versus 54+/-6,
      p<0.001) and PVN (120+/-12 versus 20+/-3, p<0.001) compared to the vehicle group
      while not influencing Fos expression in the ARC and VMH. Double labeling showed
      that 27.4+/-6.4% (n=3) of Fos-positive neurons induced by CCK-8S were positive
      for corticotropin-releasing factor immunoreactivity, that were mainly localized
      in the ventral part of the DMH, and encircled in a network of tyrosine
      hydroxylase-immunoreactive positive fibers. These data indicate that in addition
      of the PVN, peripheral CCK increases neuronal activity in the DMH suggesting a
      possible role in this hypothalamic nucleus in the satiating effect of the
      peptide.

PMID- 17005164
TI  - Electroacupuncture (EA) modulates the expression of NMDA receptors in primary
      sensory neurons in relation to hyperalgesia in rats.
AB  - N-methyl-D-aspartate (NMDA) receptor on the central terminals of the dorsal root
      ganglion (DRG) appears to be playing an important role in the development of
      central sensitization related to persistent inflammatory pain. Acupuncture
      analgesia has been confirmed by numerous clinical observations and experimental
      studies to be a useful treatment to release different kinds of pains, including
      inflammatory pain and hyperalgesia. However, the underlying mechanisms of the
      analgesic effect of acupuncture are not fully understood. In the present study,
      using a rat model of inflammatory pain induced by complete Freund's adjuvant
      (CFA), we observed the effect of electroacupuncture (EA) on animal behavior with
      regard to pain and the expression of a subunit of NMDA receptor (NR1) and
      isolectin B4 (IB4) in the neurons of the lumbar DRG. Intraplantar injection of 50
      microl CFA resulted in considerable changes in thermal hyperalgesia, edema of the
      hind paw and "foot-bend" score, beginning 5 h post-injection and persisting for a
      few days, after which a gradual recovery occurred. The changes were attenuated by
      EA treatment received on the ipsilateral "Huan Tiao" and "Yang Ling Quan" once a
      day from the first day post-injection of CFA. Using an immunofluorescence double
      staining, we found that the number of double-labeled cells to the total number of
      the IB4 and NR1-labeled neurons increased significantly on days 3 and 7 after CFA
      injection. The change was attenuated by EA treatment. These results suggest that
      EA affects the progress of experimental inflammatory pain by modulating the
      expression of NMDA receptors in primary sensory neurons, in particular, IB4
      positive small neurons.

PMID- 17005165
TI  - The limitation of IL-10-exposed dendritic cells in the treatment of experimental
      autoimmune myasthenia gravis and myasthenia gravis.
AB  - Dendritic cells (DC) are highly specialized antigen presenting cells that play
      critical roles as instigators and regulators of immune responses including B cell
      function, antibody synthesis and isotype switch. In this study, we compared
      immunotherapeutic effect of IL-10-treated DC (IL-10-DC) via both intraperitoneal
      (i.p.) and subcutaneous (s.c.) delivery in rats with incipient experimental
      autoimmune myasthenia gravis (EAMG). Spleen DC were isolated from onset of EAMG
      on day 39 post-immunization, exposed in vitro to IL-10, and then injected into
      incipient EAMG at dose of 1 x 10(6) cells/rat on day 5 after immunization.
      Intraperitoneal administration of IL-10-DC suppressed clinical scores, anti
      acetylcholine receptors (AChR) antibody secreting cells, antigen-specific IL
      10/IFN-gamma production and T cell proliferation compared to control EAMG rats.
      Importantly, IL-10-DC, if given by s.c. route, failed to ameliorate clinical sign
      of EAMG. Simultaneously, T cell proliferation, anti-AChR antibody secreting cells
      and IL-10/IFN-gamma production had no alteration, as compared to control EAMG
      rats. Both in vitro and in vivo experiments showed that treatment of IL-10
      inhibited the migration of DC toward MIP-3beta and lymph node, indicating that in
      vitro manipulation of DC with IL-10 alters the migration of DC that influences
      the therapeutic effect in the treatment of autoimmune diseases. In MG patients,
      neither the improvement of clinical symptom nor the alteration of immunological
      parameter was observed through s.c. delivery of IL-10-DC, suggesting the
      limitation of IL-10-DC in the treatment of MG patients.

PMID- 17005167
TI  - Antioxidant status and total peroxyl radical trapping antioxidant activity (TRAP)
      in cement workers.

PMID- 17005168
TI  - GSTT1 and GSTM1 allelic polymorphisms in head and neck cancer patients from
      Italian Lazio Region.
AB  - BACKGROUND: The association between head and neck squamous cell carcinoma (HNSCC)
      and allelic variants of glutathione S-transferase M1 (GSTM1) and -T1 (GSTT1) is
      currently controversial. The present study investigates the prevalences of GSTT1
      and GSTM1 polymorphism in a cohort of 100 head and neck cancer patients, 100
      healthy donors and 200 controls with non-neoplastic head and neck diseases from
      Italian Lazio Region. METHODS: The patients with benign head and neck
      pathologies, as well as the healthy donors were matched for age, sex, cigarette
      smoke (yes/no) and alcohol consumption (yes/no). Molecular definition of GSTT1
      and GSTM1 genotype has been performed by means of allele-specific PCR technique.
      RESULTS: A significant association between head and neck cancer and GSTM1 null
      genotype was observed both considering benign disease controls (p=0.001,
      OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I.
      1.69-6.67) while no significant association was found with GSTT1 null genotype
      (p>or=0.14). No interactive association was observed when combining the different
      genotypes of the two polymorphisms. These results were confirmed after correction
      for daily number of cigarettes and period of tobacco exposure. CONCLUSIONS: The
      present study confirms a role for genetic alterations of GSTM1 detoxifying enzyme
      as a risk factor for the development of HNSCC in patients from the Italian Lazio
      Region, independently of age, sex and other confounding variables.

PMID- 17005169
TI  - Immunoassay of serine-phosphorylated isoform of insulin-like growth factor (IGF)
      binding protein (IGFBP)-1.
AB  - OBJECTIVES: Development of an ELISA for phosphorylated isoform of IGFBP-1. Serine
      phosphorylation is an important regulator of IGFBP-1 bioactivity, but specific
      immunoassays for its measurement are currently lacking. DESIGN AND METHODS: Assay
      design was based on a novel approach of first capturing the phosphorylated and
      non-phosphorylated IGFBP-1 by an anti-IGFBP-1 antibody and then selectively
      detecting the phosphorylated form by an anti-phosphoserine antibody. Method
      development involved pair-wise evaluation of the candidate antibodies and
      determinations of analytical performance and specificity. Specificity was
      monitored by reactivity with dephosphorylated IGFBP-1, with antibodies against
      other phosphorylated residues that are not expressed, and by comparative analysis
      of sample containing different IGFBP-1 phosphorylation profile. RESULTS:
      Analytical evaluation demonstrated acceptable performance; detection limit 0.3
      microg/L, dynamic range 1.56-100 microg/L; intra- and inter-assay CVs 2.1-8.6%;
      mean recovery (+/-SD) 97.8+/-9.2%, and mean recovery of sample dilution 93.4+/
      6.0%. The phosphorylated and total IGFBP-1 medians in non-pregnant adult serum,
      which mostly contain the highly phosphorylated isoform, were 11.9 and 18.6
      microg/L, respectively, and the sample values were tightly correlated (r=0.99).
      As expected, the corresponding medians in 1st trimester (17.4 and 63.0 microg/L)
      and 2nd trimester (30.9 and 75.8) samples with altered IGFBP-1 phosphorylation
      were significantly different (p<0.001). Similarly, a fraction (1.29%) of total
      IGFBP-1 (13.3 mg/L) in amniotic fluids was found to be phosphorylated (0.172
      mg/L). There was no reactivity with dephosphorylated IGFBP-1. CONCLUSIONS: The
      present ELISA is highly specific for the phosphorylated isoform of IGFBP-1 and
      its availability should help expedite further investigations of IGFBP-1
      phosphorylation.

PMID- 17005170
TI  - How variable are hydroxyproline determinations made in different samples of the
      same liver?
AB  - OBJECTIVES: The haphazard distribution of fibrous tissue can interfere with
      quantitative methods for evaluating hepatic fibrosis. Inter-sample variation may
      represent a crucial issue when hydroxyproline measurement is used to quantify
      fibrosis. A comparative study of the hydroxyproline levels in normal and fibrotic
      rats is herein reported. MATERIAL AND METHODS: Twelve normal and 20 Capillaria
      hepatica-infected Wistar rats were used. Two fragments of the liver (A and B) of
      each rat were taken from separate areas and hydroxyproline measurements were
      made. Calculated differences in hydroxyproline measurements between samples from
      the same liver were analyzed by BOOTSTRAP. RESULTS: Differences in normal rats
      varied from 0.026 to 1.85 micromol of HP/g, in ten rats, the difference was less
      than 0.50 micromol. In infected rats, it varied from 0.04 to 2.86 micromol HP/g.
      Differences higher than 0.69 micromol/g were significant for normal rats (p<0.05)
      and above 1.22 micromol/g (p<0.05) for fibrotic rats. CONCLUSIONS: Hydroxyproline
      ratio in a normal liver kept a fair degree of reproducibility. In the presence of
      hepatic fibrosis, the levels of hydroxyproline may vary significantly between
      samples from a single liver and may have limited value in quantifying the extent
      of fibrosis.

PMID- 17005171
TI  - Leptin: a potential biomarker for childhood obesity?
AB  - Leptin, a hormone made by adipocytes, is an important circulating signal for the
      regulation of body weight. A review of the scientific literature (PubMed Search
      1994 to 2005) for studies examining the relationship among leptin, pediatric
      obesity and the impact of exercise intervention programmes on leptin
      concentrations are summarized. The potential utility of leptin as a biomarker for
      identifying children at risk of obesity is discussed. This literature review
      demonstrated that (1) leptin directly interacts with the hypothalamus for energy
      balance regulation; (2) the measurement of free, bound and total leptin as well
      as soluble leptin receptor concentration are critical for our understanding of
      obesity in children; and (3) leptin concentration may be an important factor for
      determining intervention programme responsiveness in pediatric obesity.

PMID- 17005173
TI  - Different inflammatory mediators induce inflammation and pain after application
      of liquid nitrogen to the skin.
AB  - The application of liquid nitrogen to the skin induces inflammation and pain.
      However, there is little data on the role of inflammatory mediators in the
      production of these symptoms. We have developed an experimental model to study
      some aspects of the inflammatory response and its mediators following the
      application of cold. We have applied liquid nitrogen jets to subcutaneous air
      pouches in the dorsal skin of rats to study the kinetics of the migration of
      inflammatory cells; also to the ear for histopathological analysis and on the
      paws for edema and pain. Inflammatory mediators were identified by
      pharmacological means. The results showed that the cellular inflammatory response
      was characterized by persistent cell migration, mainly of granulocytes.
      Histopathology of the ears confirmed these findings. Histamine and
      sympathomimetic mediators were mainly responsible for the resultant swelling.
      However, the hypernociception that resulted involved other mediators including IL
      1 and eicosanoids. These data suggest that interference with the release of
      inflammatory mediators might reduce the side effects of cryosurgery and prevent
      hyperalgesia and inflammation at the site of application of cold.

PMID- 17005174
TI  - Dishevelled proteins regulate cell adhesion in mouse blastocyst and serve to
      monitor changes in Wnt signaling.
AB  - Wnt signaling is essential for the regulation of cell polarity and cell fate in
      the early embryogenesis of many animal species. Multiple Wnt genes and its
      pathway members are expressed in the mouse early embryo, raising the question
      whether they play any roles in preimplantation development. Dishevelled is an
      important transducer of divergent Wnt pathways. Here we show that three of the
      mouse Dishevelled proteins are not only expressed in oocytes and during
      preimplantation development, but also display distinct spatio-temporal
      localization. Interestingly, as embryos reach blastocyst stage, Dishevelled 2
      becomes increasingly associated with cell membrane in trophectoderm cells, while
      at E4.5, Dishevelled 3 is highly enriched in the cytoplasm of ICM cells. These
      changes are coincident with an increase in the active form of beta-catenin,
      p120catenin transcription and decrease of Kaiso expression, indicating an
      upregulation of Wnt signaling activity before implantation. When Dishevelled-GFP
      fusion proteins are overexpressed in single blastomeres of the 4-cell stage
      embryo, the progeny of this cell show reduction in cell adhesiveness and a
      rounded shape at the blastocyst stage. This suggests that perturbing Dvl function
      interferes with cell-cell adhesion through the non-canonical Wnt pathway in
      blastocysts.

PMID- 17005175
TI  - TrkB/BDNF signaling regulates photoreceptor progenitor cell fate decisions.
AB  - Neurotrophins, via activation of Trk receptor tyrosine kinases, serve as
      mitogens, survival factors and regulators of arborization during retinal
      development. Brain-derived neurotrophic factor (BDNF) and TrkB regulate neuronal
      arborization and survival in late retinal development. However, TrkB is expressed
      during early retinal development where its functions are unclear. To assess
      TrkB/BDNF actions in the early chick retina, replication-incompetent retroviruses
      were utilized to over-express a dominant negative truncated form of TrkB (trunc
      TrkB), or BDNF and effects were assessed at E15. Clones expressing trunc TrkB
      were smaller than controls, and proliferation and apoptosis assays suggest that
      decreased clone size correlated with increased cell death when BDNF/TrkB
      signaling was impaired. Analysis of clonal composition revealed that trunc TrkB
      over-expression decreased photoreceptor numbers (41%) and increased cell numbers
      in the middle third of the inner nuclear layer (INL) (23%). Conversely, BDNF over
      expression increased photoreceptor numbers (25%) and decreased INL numbers (17%).
      Photoreceptors over-expressing trunc TrkB demonstrated no increase in apoptosis
      nor abnormalities in lamination suggesting that TrkB activation is not required
      for photoreceptor cell survival or migration. These studies suggest that TrkB
      signaling regulates commitment to and/or differentiation of photoreceptor cells
      from retinal progenitor cells, identifying a novel role for TrkB/BDNF in
      regulating cell fate decisions.

PMID- 17005177
TI  - BMPs restrict the position of premuscle masses in the limb buds by influencing
      Tcf4 expression.
AB  - Previous studies have shown the distally retreating source of Scatter
      factor/Hepatocyte growth factor (SF/HGF) can account for the distal migration of
      myogenic precursor cells in the limb bud mesenchyme. However, the normal
      expression pattern of Sf/Hgf alone does not explain the distribution of muscle
      precursor cells. Hence, the position of the dorsal and ventral premuscle masses
      suggests the presence of additional patterning factors. We present evidence that
      BMP2 and 4 can act as such factors by inhibiting the expression of Tcf4, a
      downstream element of the canonical Wnt pathway. The normal position of muscle
      cells depends on the correct distribution of BMP and SF/HGF throughout the limb
      bud mesenchyme. Removal or inhibition of the BMP signals within the limb margins
      leads to a shift in position resulting in the fusion of the dorsal and ventral
      premuscle masses towards the manipulated areas. In the absence of BMPs,
      mispositioning requires the presence of SF/HGF. Consequently, ectopic application
      of exogenous SF/HGF in the presence of BMP signals does not change muscle
      positioning. We conclude that correct positioning of the premuscle masses in the
      limb buds is controlled by the combined influence of SF/HGF signals--guiding
      cells mainly in the proximo-distal axis--and BMP signals that restrict the
      positioning to the dorsal and ventral central portions of the limb buds.

PMID- 17005176
TI  - Role of T-box gene tbx-2 for anterior foregut muscle development in C. elegans.
AB  - During organogenesis, pluripotent precursor cells acquire a defined identity such
      as muscle or nerve. The transition from naive precursor towards the
      differentiated state is characterized by sequential waves of gene expression that
      are determined by regulatory transcription factors. A key question is how
      transcriptional circuitry dictates the succession of events that accompanies
      developmental competence, cell fate specification and differentiation. To address
      this question, we have examined how anterior muscles are established within the
      Caenorhabditis elegans foregut (pharynx). We find that the T-box transcription
      factor tbx-2 is essential to form anterior pharyngeal muscles from the ABa
      blastomere. In the absence of tbx-2 function, ABa-derived cells initiate
      development normally: they receive glp-1/Notch signaling cues, activate the T-box
      gene TBX-38 and express the organ selector gene PHA-4/FoxA. However, these cells
      subsequently arrest development, extinguish PHA-4 and fail to activate PHA-4
      target genes. tbx-2 mutant cells do not undergo apoptosis and there is no
      evidence for adoption of an alternative fate. TBX-2 is expressed in ABa
      descendants and depends on activation by pha-4 and repression by components of
      glp-1/Notch signaling. Our analysis suggests that a positive feedback loop
      between tbx-2 and pha-4 is required for ABa-derived precursors to commit to
      pharyngeal muscle fate.

PMID- 17005178
TI  - Immunodeficient mice have elevated numbers of NK cells in non-lymphoid tissues.
AB  - Natural killer (NK) cells are an important part of the innate immune response.
      They have the ability to recognize and kill many types of tumor cells and promote
      immunity against intracellular pathogens. In this study, we analyzed the in situ
      localization of NK cells within wildtype and immunodeficient mice using a novel
      in situ analysis method. We have identified NK cells in tissues of B6 and
      B6.Rag1(-/-) mice and demonstrated an increase in the percentage of NK cells and
      the total number of NK cells in the lung and liver of immunodeficient mice. This
      increase was not due to an increase in NK cell activation. This study describes a
      means to identify NK cells within complex tissue environments, and the increase
      in NK cells in non-lymphoid tissues may explain much of the increased NK cell
      activity observed in T-cell-deficient mice.

PMID- 17005179
TI  - Intravenous paclitaxel administration in the rat induces a peripheral sensory
      neuropathy characterized by macrophage infiltration and injury to sensory neurons
      and their supporting cells.
AB  - Paclitaxel-induced peripheral neuropathy (PN) can be a significant problem for
      patients receiving chemotherapeutic regimens for the treatment of breast,
      ovarian, and lung cancer as PN can influence the quality of life and survivorship
      in these patients. To begin to understand the cellular changes that occur within
      the peripheral and central nervous system as PN develops, we intravenously
      infused rats with clinically relevant doses of paclitaxel. Ten days later,
      behavioral changes indicative of PN became evident that included mechanical
      allodynia, cold hyperalgesia, and deficits in ambulation/coordination. These
      behaviors were accompanied by increased expression of activating transcription
      factor 3 (ATF3; a marker of cellular injury) in a population of
      large>medium>small diameter sensory neurons, a population of satellite cells in
      the lumbar dorsal root ganglia (DRG) and in myelinating Schwann cells in the
      sciatic nerve. In addition, there was an increase in the expression of glial
      fibrillary acidic protein (GFAP) in DRG satellite cells and an increase in the
      number of CD68 positive activated macrophages within the DRG and peripheral
      nerve. Within lamina III-IV of the lumbar spinal cord, there was an increase in
      OX42 positive microglia. These data suggest that intravenous infusion of
      paclitaxel induces a peripheral neuropathy characterized by injury of neuronal
      and non-neuronal cells in the peripheral nervous system, macrophage activation in
      both the DRG and peripheral nerve, and microglial activation within the spinal
      cord. An understanding of the factors involved in the development and maintenance
      of PN may lead to mechanism based therapies that prevent/treat PN and thus
      improve the survival and quality of life of patients receiving chemotherapy.

PMID- 17005180
TI  - Neuroprotection by estradiol: a role of aromatase against spine synapse loss
      after blockade of GABA(A) receptors.
AB  - Estrogen has been suggested to be pro-epileptic by reducing GABA synthesis,
      resulting in increased spine density and a decreased threshold for seizures in
      the hippocampus, which, once they occur, are characterized by a dramatic spine
      loss in the affected brain areas. As considerable amounts of estradiol are
      synthesized in the hippocampus, in this study we focused on aromatase, the rate
      limiting enzyme in estrogen synthesis in order to examine the role of locally
      synthesized estrogens in epilepsy. To this end, we first examined the effects of
      letrozole, a potent aromatase inhibitor, on GABA metabolism in single
      interneurons of hippocampal dispersion cultures. Letrozole downregulated
      estradiol release into the medium, as well as glutamate decarboxylase (GAD)
      expression and GABA synthesis, and decreased the number of GAD positive cells in
      the cultures. Next, we counted spine synapses and measured estradiol release of
      hippocampal slice cultures, in which GABA(A) receptors had been blocked by
      bicuculline, in order to mimic epileptic activity. Treatment of slice cultures
      with bicuculline resulted in a dramatic decrease in the number of spine synapses
      and in a significant suppression of estrogen synthesis. The decrease in synapse
      number in response to bicuculline was restored by combined application of
      estradiol and bicuculline. Surprisingly, estradiol alone had no effect on either
      spine synapse number or on GAD expression and GABA synthesis. "Rescue" of synapse
      number in "epileptic slices" by estradiol and maintenance of GABA metabolism by
      hippocampus-derived estradiol points to a neuroprotective role of aromatase in
      epilepsy. Re-filling of estradiol stores after their depletion due to
      overexcitation may therefore add to therapeutical strategies in epilepsy.

PMID- 17005181
TI  - Cloning and characterization of the retinoid X receptor from a primitive
      crustacean Daphnia magna.
AB  - Terpenoid hormones function as morphogens throughout the animal kingdom and many
      of these activities are mediated through members of the retinoid X group of
      nuclear receptors (RXR; NR2B). In the present study, RXR was cloned from the
      water flea Daphnia magna, a primitive crustacean of the class Branchiopoda, and
      characterized with respect to phylogeny, developmental expression, and hormonal
      regulation. The full length daphnid RXR cDNA was cloned by initial PCR
      amplification of a cDNA fragment from the highly conserved DNA-binding domain
      followed by extension of the fragment using RACE PCR. The full length cDNA was
      1888 base pairs in length and coded for a 400 amino acid protein that exhibited
      the five-domain structure of a nuclear receptor superfamily member. The RXR
      protein shared significant identity with other NR2B group members. Phylogenetic
      analyses of the ligand-binding domain of the receptor revealed that daphnid RXR
      clustered with RXR from decapod crustaceans on a branch of the phylogenetic tree
      that was distinct from RXRs known to bind retinoic acids and juvenile hormones.
      Daphnid RXR mRNA levels were greatest in embryos that were early in development
      and progressively declined through the initial five stages of embryo development.
      Adult females expressed higher levels of RXR mRNA than did males and exposure of
      females to the terpenoid mimic pyriproxyfen reduced RXR mRNA to levels
      approaching levels in males. RXR mRNA levels in males were refractory to
      pyriproxyfen. These results show that branchiopod crustaceans dynamically express
      RXR which should be evaluated as a candidate receptor for the terpenoid hormone
      methyl farnesoate which functions as a sex determinant in these organisms.

PMID- 17005182
TI  - Implementing holistic practices in mental health nursing: a national
      consultation.
AB  - BACKGROUND: A national consultation exercise was held as part of a review of
      mental health nursing in England. OBJECTIVES: To gather views as to how best to
      develop mental health nursing to support a holistic approach to care, taking into
      account psychological, physical social and spiritual needs. DESIGN: National open
      consultation by email over a 3-month period. PARTICIPANTS: 326 written replies
      were received. The largest group of responses was from National Health Service
      (NHS) organisations (n=92, 28.2%); 69.9% of responses were from groups or
      organisations (n=225). METHODS: A consultation document was devised by a national
      reference group, including four questions relating to the development of practice
      in the four domains of: psychological, physical, social and spiritual care.
      RESULTS: The majority of responses supported mental health nurses (MHNs)
      providing psychological therapies (n=271, 95.1%). To support this happening,
      responders most frequently described a need for appropriate specialist training
      post-registration (n=114). To improve physical well-being of service users, the
      most frequent suggestion was that MHNs should promote healthy lifestyles, e.g. by
      encouraging physical activity and advising on ways to reduce illicit drug,
      alcohol and tobacco use (n=152). Responders most frequently cited the need for
      MHNs to understand resources to support social inclusion (n=110), e.g. knowing
      how to access local resources, benefits, housing and employment advice. MHNs were
      most frequently seen as requiring appropriate training to help them support
      spiritual/religious needs (n=96). CONCLUSIONS: The consultation was successful in
      obtaining views, in particular, of organisations and groups. These subsequently
      influenced national recommendations made by the Chief Nursing Officer's Review of
      Mental Health Nursing.

PMID- 17005183
TI  - Current perspectives on the mechanism of action of artemisinins.
AB  - Artemisinin derivatives are the most recent single drugs approved and introduced
      for public antimalarial treatment. Although their recommended use is for
      treatment of Plasmodium falciparum infection, these drugs also act against other
      parasites, as well as against tumor cells. The mechanisms of action attributed to
      artemisinin include interference with parasite transport proteins, disruption of
      parasite mitochondrial function, modulation of host immune function and
      inhibition of angiogenesis. Artemisinin combination therapies are currently the
      preferred treatment for malaria. These combinations may prevent the induction of
      parasite drug resistance. However, in view of the multiple mechanisms involved,
      especially when additional drugs are used, the combined therapy should be
      carefully examined for antagonistic effects. It is now a general theory that the
      crucial mechanism is interference with plasmodial SERCA. Therefore, future
      development of resistance may be associated with overproduction or mutations of
      this transporter. However, a general mechanism, such as alterations in general
      drug transport pathways, is feasible. In this article, we review the evidence for
      each mechanism of action suggested.

PMID- 17005184
TI  - Effect of the quinolone coccidiostat decoquinate on the rearrangement of
      chromosomes of Eimeria tenella.
AB  - The present report concerns our attempts to further study the effect of quinolone
      coccidiostats on the sporulation of Eimeria tenella oocysts by analyzing the
      meiotic behaviour of the chromosomes. To that end, synaptonemal complexes were
      analyzed by TEM applied to intact meiotic chromosomes. These were isolated after
      disruption of oocysts, which were harvested from decoquinate-medicated and non
      medicated (control) birds. In oocysts from control birds, synaptonemal complexes
      appeared as the 14 bivalents of the normal karyotype. However, in oocysts from
      medicated birds, our synaptonemal complex analysis revealed a reciprocal
      translocation, which was observed as an irregular pairing of chromosome axes 5
      and 12 resulting in quadrivalent and trivalent configurations. This finding
      suggests breakage points in chromosomes 5 and 12 and exchange of chromosomal
      segments. Furthermore, breakpoints in chromosome 12 resulted in telomere
      deletion. The chromosomal aberrations described in the present study may result
      in reduced sporulation since chromosomes involved in translocations segregate
      abnormally during meiosis. In addition, the results reported provide new evidence
      of the inhibitory effect of quinolones on the sporulation of E. tenella oocysts,
      since sporocysts were not formed.

PMID- 17005186
TI  - Intracellular labeling method for chip-based capillary electrophoresis
      fluorimetric single cell analysis using liposomes.
AB  - An intracellular derivatization method mediated by liposome was developed for
      single cell analysis with chip-based capillary electrophoresis (CE) and laser
      induced fluorescence (LIF) detection. Liposomes with an average diameter of 100
      nm were produced from phosphatidylcholine to encapsulate fluorescent dyes by an
      ultrasonic method. The encapsulation yield and the vesicle density were
      determined to be 46+/-5% and 8.8 x 10(14)/mL, respectively. The amount of
      fluorescent dye that entered the cells was dependent on the duration of
      incubating cells with liposomes, liposome density, and concentration of the dye
      solution encapsulated in liposomes. The described method introduced cell membrane
      nonpermeable fluorescent dyes into living cells without reducing cell viability.
      Single cell analysis using microfluidic chip-based CE revealed that liposome
      membrane fusion occurred after entrance of liposomes into the cells, with release
      of encapsulated fluorescence dyes and labeling of intracellular species.

PMID- 17005185
TI  - AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to
      HDL.
AB  - BACKGROUND: Previous reports have suggested that advanced glycation end products
      (AGE) participate in the pathogenesis of diabetic macroangiopathy. However,
      current understanding of the mechanisms by which AGE may accelerate atherogenesis
      remains incomplete. METHODS AND RESULTS: Microarray and reverse transcription
      real-time PCR analyses revealed that exposure to AGE-BSA (BSA, bovine serum
      albumin) reduced mRNA levels (60%) in the ATP-binding cassette transporter G1
      (ABCG1) but not ABCA1 in human macrophages. AGE-BSA also reduced ABCG1 protein
      levels. These effects occurred mainly through the receptor for AGE (RAGE), as an
      anti-RAGE antibody significantly limited ABCG1 mRNA reduction. Functional studies
      demonstrated that exposure to AGE-BSA decreased cholesterol efflux to high
      density lipoprotein (HDL) (P<0.05) but not to apolipoprotein AI, compared to BSA
      treatment. Although liver X receptors (LXR) augment ABCG1 expression, macrophages
      treated with AGE-BSA showed no reduction in LXR mRNA levels or in the binding of
      nuclear proteins to the LXR response element, compared with BSA. CONCLUSIONS: Our
      data show that AGE-BSA can decrease cholesterol efflux from macrophages to HDL
      via an LXR-independent pathway. This novel mechanism may contribute to
      accelerated foam cell production and atherogenesis in diabetic patients.

PMID- 17005187
TI  - Pyrethroids, pyrethrins, and piperonyl butoxide in sediments by high-resolution
      gas chromatography/high-resolution mass spectrometry.
AB  - A new method for determination of pyrethroids, pyrethrins, and piperonyl butoxide
      (PBO) by high-resolution gas chromatography/high-resolution mass spectrometry
      (HRGC/HRMS) was developed for aquatic sediments. The method detection limits for
      pyrethroids (15 compounds), pyrethrins, and PBO ranged from 0.16 to 1.50 ng/g
      sediment, which was suitable for detecting these chemicals at environmentally
      relevant concentrations (low ng/L range) that are toxicologically significant to
      benthic organisms. Recovery of the analytes from a low level spiked sediment
      ranged from 89.7% to 135%. Resmethrin showed the lowest recovery at 23.5% and
      pyrethrins showed the highest recovery at 154%. To confirm the utility of this
      new method for environmental applications, sediment samples collected from five
      tributaries of the San Francisco Bay, California were analyzed. Individual
      pyrethroids were detected in concentrations of up to 17.6 ng/g, while PBO was
      detected in all sediment samples in concentrations of 0.010-0.215 ng/g.
      Pyrethrins were not found in the sediment samples.

PMID- 17005188
TI  - Chiral separation of lipoxygenase metabolites utilizing high-performance liquid
      chromatography.
AB  - An isocratic, reversed-phase HPLC assay has been developed for the separation of
      the enantiomers of four lipoxygenase metabolites, without the need for a
      derivatization step. Separation of the enantiomers was studied on a
      polysaccharide type chiral stationary phase column. Upon determination of
      suitable mobile phase composition, the assay was evaluated at various
      temperatures. In all cases the R enantiomer eluted before the S enantiomer. The
      best separations were observed at 0 degrees C.

PMID- 17005189
TI  - Effect of quaternary ammonium cations on dye sorption to fly ash from aqueous
      media.
AB  - The efficacy of the surface modification of fly ash by quarternary ammonium
      cations in the removal of dyes from aqueous solution is demonstrated. A series of
      organo-fly ash materials were synthesized by treating fly ash with quarternary
      ammonium cations such as tetraethylammonium, hexadecyltrimethylammonium, and
      benzyldimethyltetradecylammonium (TEA, HDTMA, and BDTDA). Two types of dyes were
      used for the investigation, disperse and anionic dyes. The effects of initial dye
      concentration, contact time, temperature, and the mechanism of dye sorption were
      investigated. The sorption was found to be affected by the structure and size of
      the quaternary ammonium cations as well as that of the dyes. Sorption of dyes was
      considerably enhanced by the surface modification. Thermodynamic parameters such
      as free energy (DeltaG0), enthalpy (DeltaH0), and entropy (DeltaS0) for the
      sorption process were also calculated.

PMID- 17005190
TI  - The adsorption and reaction of a titanate coupling reagent on the surfaces of
      different nanoparticles in supercritical CO2.
AB  - The adsorption and reaction in supercritical CO2 of the titanate coupling reagent
      NDZ-201 on the surfaces of seven metal oxide particles, SiO2, Al2O3, ZrO2, TiO2
      (anatase), TiO2 (rutile), Fe2O3, and Fe3O4, was investigated. FTIR and TG
      analysis indicated that the adsorption and reaction were different on different
      particle surfaces. On SiO2 and Al2O3 particles, there was a chemical reaction of
      the titanate coupling reagent on the surfaces. On the surfaces of ZrO2 and TiO2
      (anatase) particles, there were two kinds of adsorption, weak and strong
      adsorption. On the surfaces of TiO2 (rutile), Fe2O3, and Fe3O4 particles, there
      was only weak adsorption. The acidity or basicity of the OH groups on the
      particle surface was the key factor that determined if a surface reaction
      occurred. When the OH groups were acidic, the titanate coupling reagent reacted
      with these, but otherwise, there was no reaction. The surface density of OH
      groups on the original particles and the amount of titanate coupling reagent
      adsorbed and reacted were estimated from TG analysis. The reactivity of the
      surface OH groups of Al2O3 particles was higher than that of the SiO2 particles.

PMID- 17005191
TI  - Cytological variation and pathogenicity of the bumble bee parasite Nosema bombi
      (Microspora, Nosematidae).
AB  - In three field seasons, 2003-2005, bumble bees were collected in southern Sweden
      and eastern Denmark in search of microsporidian parasites. Of the 16 bumble bee
      species studied, microsporidia were found in Bombus hortorum, Bombus hypnorum,
      Bombus lapidarius, Bombus lucorum, Bombus pascuorum, Bombus pratorum, Bombus
      ruderarius, Bombus subterraneus and Bombus terrestris. Only one microsporidian
      species, Nosema bombi, was recorded. A microsporidium found in B. pratorum
      differed cytologically from microsporidia of the other host species. In the most
      frequently infected host, B. terrestris, the prevalence was 20.6%. Totally 1049
      specimens were dissected. The light microscopic and ultrastructural cytology and
      pathology of N. bombi is described with focus on the variation recorded.
      Variation was especially prominent in the shape, size and coupling of spores, and
      in the length and arrangement of the polar filament. In four host species
      microsporidian infection was restricted to peripheral fat cells.

PMID- 17005192
TI  - Recovery of Bacillus thuringiensis in vegetative form from the phylloplane of
      clover (Trifolium hybridum) during a growing season.
AB  - Two media were developed which specifically allow the cultivation of Bacillus
      thuringiensis while it is in the vegetative as opposed to the spore form. Using
      these media B. thuringiensis was shown conclusively for the first time to exist
      in an active form on the phylloplane. The profile of its appearance in vegetative
      and spore form was followed over a growing season on clover (Trifolium hybridum)
      in the field. Three simultaneous and sudden rises and declines of both spore and
      vegetative cell densities were observed. The most common other spore-former on
      these leaves was Bacillus cereus but the fluctuations in appearance of these two
      very closely related species were not co-incident. Using specific PCR primers a
      considerable diversity of cry toxin gene types was found in isolates that had
      been recovered in vegetative form ('vegetative isolates') with the majority
      possessing multiple delta-endotoxin genes while some had only one of those
      tested. Bioassays against a lepidopteran insect of purified delta-endotoxins
      showed that they were no more potent than those from a laboratory-adapted strain.
      PCR primers for an internal region of the vip3A gene produced amplification in
      70% of the vegetative isolates compared to 25% of the laboratory-adapted strains
      tested.

PMID- 17005193
TI  - Microsporidia-insect host interactions: teratoid sporogony at the sites of host
      tissue melanization.
AB  - Microsporidia Paranosema locustae and Paranosema grylli infect fat bodies of
      orthopteran hosts Locusta migratoria and Gryllus bimaculatus, respectively, and
      cause formation of nodules consisting of deposits of melanin around heavily
      infected cells. Both species sporadically produce enlarged or malformed
      (teratoid) spores as a result of abnormal sporogony. Proportions of teratospores
      within melanized nodules were 6-10 times higher than in surrounding non-melanized
      tissues. The increased numbers of teratoid microsporidian spores within melanized
      regions may indicate the deteriorating effect of melanin metabolites on spore
      morphogenesis.

PMID- 17005194
TI  - Soil mediates the interaction of coexisting entomopathogenic nematodes with an
      insect host.
AB  - We tested for soil substrate effects on the movement and infectivity of naturally
      co-occurring entomopathogenic nematodes Steinernema feltiae and Heterorhabditis
      marelatus, alone and in combination. We manipulated the presence and bulk density
      of soil and added Galleria mellonella baits within capped and perforated 15mL
      centrifuge tubes. Sampling tubes were then deployed in situ into field and
      laboratory settings as experimental traps for infective juveniles. In comparisons
      with standard soil collections from Lupinus arboreus rhizospheres, sampling tubes
      were equally sensitive to the presence of H. marelatus and more sensitive to S.
      feltiae. In laboratory microcosms, both EPN species infected Galleria at high
      frequencies in tubes lacking soil and in the absence of heterospecifics.
      Infection frequency of S. feltiae was unaffected by the presence of H. marelatus,
      but it declined with higher soil bulk density inside tubes. In contrast,
      detectable infection frequency by H. marelatus was reduced only marginally by the
      presence of soil but severely by the presence of S. feltiae. Thus, the presence
      of soil in tubes reversed the identity of dominant species infecting Galleria in
      tubes, an effect magnified when soils were compacted. Moreover, S. feltiae rarely
      moved into tubes lacking Galleria baits, whereas H. marelatus colonized unbaited
      tubes 4- to 5-fold more frequently than S. feltiae. In situ, sampling tubes acted
      as filters to reduce interference and contamination by fungal pathogens common in
      field soils. The method allows precision sampling with minimal soil disturbance
      while protecting bait insects from scavengers. Manipulation of tube design may
      allow selective sampling of EPN species, depending on the abiotic characteristics
      of soils, and the biology, behavior, and interspecific interactions of coexisting
      species.

PMID- 17005195
TI  - Neuregulin-1 beta attenuates doxorubicin-induced alterations of excitation
      contraction coupling and reduces oxidative stress in adult rat cardiomyocytes.
AB  - Treatment of metastatic breast cancer with doxorubicin (Doxo) in combination with
      trastuzumab, an antibody targeting the ErbB2 receptor, results in an increased
      incidence of heart failure. Doxo therapy induces reactive oxygen species (ROS)
      and alterations of calcium homeostasis. Therefore, we hypothesized that
      neuregulin-1 beta (NRG), a ligand of the cardiac ErbB receptors, reduces Doxo
      induced alterations of EC coupling by triggering antioxidant mechanisms. Adult
      rat ventricular cardiomyocytes (ARVM) were isolated and treated for 18-48 h.
      SERCA protein was analyzed by Western blot, EC coupling parameters by fura-2 and
      video edge detection, gene expression by RT-PCR, and ROS by DCF-fluorescence
      microscopy. At clinically relevant doses Doxo reduced cardiomyocytes
      contractility, SERCA protein and SR calcium content. NRG, similarly as the
      antioxidant N-acetylcystein (NAC), did not affect EC coupling alone, but
      protected against Doxo-induced damage. NRG and Doxo showed an opposite modulation
      of glutathione reductase gene expression. NRG, similarly as NAC, reduced peroxide
      or Doxo-induced oxidative stress. Specific inhibitors showed, that the
      antioxidant action of NRG depended on signaling via the ErbB2 receptor and on the
      Akt- and not on the MAPK-pathway. Therefore, NRG attenuates Doxo-induced
      alterations of EC coupling and reduces oxidative stress in ARVM. Inhibition of
      the ErbB2/NRG signaling pathway by trastuzumab in patients concomitantly treated
      with Doxo might prevent beneficial effects of NRG in the myocardium.

PMID- 17005196
TI  - Opposing cardiovascular roles for the angiotensin and apelin signaling pathways.

PMID- 17005197
TI  - Sequence identity of the direct repeats, DR1 and DR2, contributes to the
      discrimination between primer translocation and in situ priming during
      replication of the duck hepatitis B virus.
AB  - There are two mutually exclusive pathways for plus-strand DNA synthesis in
      hepadnavirus reverse transcription. The predominant pathway gives rise to relaxed
      circular DNA, while the other pathway yields duplex linear DNA. At the completion
      of minus-strand DNA synthesis, the final RNase H cleavage generates the plus
      strand primer at direct repeat 1 (DR1). A small fraction of viruses make duplex
      linear DNA after initiating plus-strand DNA synthesis from this site, a process
      called in situ priming. To make relaxed circular DNA, a template switch is
      necessary for the RNA primer generated at DR1 to initiate plus-strand DNA
      synthesis from the direct repeat 2 (DR2) located near the opposite end of the
      minus-strand DNA, a process called primer translocation. We are interested in
      understanding the mechanism that discriminates between these two processes.
      Previously, we showed that a small DNA hairpin forms at DR1 in the
      avihepadnaviruses and acts as an inhibitor of in situ priming. Here, using
      genetic approaches, we show that sequence identity between DR1 and DR2 is
      necessary, but not sufficient for primer translocation in the duck hepatitis B
      virus. The discrimination between in situ priming and primer translocation
      depends upon suppression of in situ priming, a process that is dependent upon
      both sequence identity between DR1 and DR2, and the presence of the hairpin at
      DR1. Finally, our analysis indicates the entire RNA primer can contribute to
      primer translocation and is translocated to DR2 before initiation of plus-strand
      DNA synthesis from that site.

PMID- 17005198
TI  - A new structural domain in the Escherichia coli RcsC hybrid sensor kinase
      connects histidine kinase and phosphoreceiver domains.
AB  - The Rcs signalling pathway controls a variety of physiological functions like
      capsule synthesis, cell division or motility in prokaryotes. The Rcs regulation
      cascade, involving a multi-step phosphorelay between the two membrane-bound
      hybrid sensor kinases RcsC and RcsD and the global regulator RcsB, is, up to now,
      one of the most complicated regulatory systems in bacteria. To understand the
      structural basis of Rcs signal transduction, NMR spectroscopy was employed to
      determine the solution structure of the RcsC C terminus, possessing a
      phosphoreceiver domain (RcsC-PR), and a region previously described as a long
      linker between the histidine kinase domain of RcsC (RcsC-HK) and the RcsC-PR. We
      have found that the linker region comprises an independent structural domain of a
      new alpha/beta organization, which we named RcsC-ABL domain (Alpha/Beta/Loop).
      The ABL domain appears to be a conserved and unique structural element of RcsC
      like kinases with no significant sequence homology to other proteins. The second
      domain of the C terminus, the RcsC-PR domain, represents a well-folded CheY-like
      phosphoreceiver domain with the central parallel beta-sheet covered with two
      alpha-helical layers on both sides. We have mapped the interaction of RcsC-ABL
      and RcsC-PR with the histidine phosphotransfer domain (HPt) of RcsD. In addition
      we have characterized the interaction with and the conformational effects of Mg2+
      and the phosphorylation mimetic BeF(-)(3) on RcsC-ABL and RcsC-PR.

PMID- 17005199
TI  - Lipidic sponge phase crystallization of membrane proteins.
AB  - Bicontinuous lipidic cubic phases can be used as a host for growing crystals of
      membrane proteins. Since the cubic phase is stiff, handling is difficult and time
      consuming. Moreover, the conventional cubic phase may interfere with the
      hydrophilic domains of membrane proteins due to the limited size of the aqueous
      pores. Here, we introduce a new crystallization method that makes use of a liquid
      analogue of the cubic phase, the sponge phase. This phase facilitates a
      considerable increase in the allowed size of aqueous domains of membrane
      proteins, and is easily generalised to a conventional vapour diffusion
      crystallisation experiment, including the use of nanoliter drop crystallization
      robots. The appearance of the sponge phase was confirmed by visual inspection,
      small-angle X-ray scattering and NMR spectroscopy. Crystals of the reaction
      centre from Rhodobacter sphaeroides were obtained by a conventional hanging-drop
      experiment, were harvested directly without the addition of lipase or
      cryoprotectant, and the structure was refined to 2.2 Angstroms resolution. In
      contrast to our earlier lipidic cubic phase reaction centre structure, the mobile
      ubiquinone could be built and refined. The practical advantages of the sponge
      phase make it a potent tool for crystallization of membrane proteins.

PMID- 17005200
TI  - Quasi-symmetry in the cryo-EM structure of EmrE provides the key to modeling its
      transmembrane domain.
AB  - Small multidrug resistance (SMR) transporters contribute to bacterial resistance
      by coupling the efflux of a wide range of toxic aromatic cations, some of which
      are commonly used as antibiotics and antiseptics, to proton influx. EmrE is a
      prototypical small multidrug resistance transporter comprising four transmembrane
      segments (M1-M4) that forms dimers. It was suggested recently that EmrE molecules
      in the dimer have different topologies, i.e. monomers have opposite orientations
      with respect to the membrane plane. A 3-D structure of EmrE acquired by electron
      cryo-microscopy (cryo-EM) at 7.5 Angstroms resolution in the membrane plane
      showed that parts of the structure are related by quasi-symmetry. We used this
      symmetry relationship, combined with sequence conservation data, to assign the
      transmembrane segments in EmrE to the densities seen in the cryo-EM structure. A
      C alpha model of the transmembrane region was constructed by considering the
      evolutionary conservation pattern of each helix. The model is validated by much
      of the biochemical data on EmrE with most of the positions that were identified
      as affecting substrate translocation being located around the substrate-binding
      cavity. A suggested mechanism for proton-coupled substrate translocation in small
      multidrug resistance antiporters provides a mechanistic rationale to the
      experimentally observed inverted topology.

PMID- 17005201
TI  - Direct observation of oligomeric species formed in the early stages of amyloid
      fibril formation using electrospray ionisation mass spectrometry.
AB  - Numerous debilitating human disorders result from protein misfolding and amyloid
      formation. Despite the grave nature of these maladies, our understanding of the
      structural mechanism of fibril assembly is limited. Of paramount importance is
      the need to identify and characterize oligomeric species formed early during
      fibril assembly, so that the nature of the initiating assembly mechanism can be
      revealed and species that may be toxic to cells identified. However, the
      transient nature of early oligomeric species, combined with their heterogeneity
      and instability, has precluded detailed analysis to date. Here, we have used
      electrospray ionisation mass spectrometry (ESI-MS), complemented by analytical
      ultracentrifugation (AUC) and measurements of thioflavin-T fluorescence, to
      monitor the early stages of assembly of amyloid-like fibrils formed from human
      beta-2-microglobulin (beta2m) in vitro. We show that worm-like fibrils that form
      with nucleation-independent kinetics assemble by a mechanism consistent with
      monomer addition, with species ranging from monomer to > or = 13-mer being
      identified directly and uniquely as transient assembly intermediates. By
      contrast, only monomers, dimers, trimers and tetramers are observed during
      nucleated growth, which leads to the formation of long straight fibrils. The
      results highlight the unique power of non-covalent ESI-MS to identify protein
      assembly intermediates in complex heterogeneous systems and demonstrate its great
      potential to identify and characterise individual species formed early during
      amyloid assembly.

PMID- 17005202
TI  - CSF orexin levels of Parkinson's disease, dementia with Lewy bodies, progressive
      supranuclear palsy and corticobasal degeneration.
AB  - Excessive daytime sleepiness has been widely accepted as a common problem not
      only in Parkinson's disease (PD) but also in other related disorders. Lowered
      excretion of orexin A (hypocretin 1) into the cerebrospinal fluid (CSF) is known
      to play a pathological role in narcolepsy and secondary hypersomnia due to
      hypothalamic dysfunction. Although the levels of CSF orexin in PD have been
      previously examined, the results have been controversial, and no systematic
      investigation of CSF orexin excretion has been conducted on PD related disorders.
      In this study, orexin was measured in CSF collected by lumbar puncture in 62
      patients with PD, 13 patients with dementia with Lewy bodies (DLB), 16 patients
      with progressive supranuclear palsy (PSP), and 7 patients with corticobasal
      degeneration (CBD). Levels of CSF orexin (mean+/-SD pg/ml) were 302+/-38 in PD,
      297+/-48 in DLB, 258+/-37 in PSP, 246+/-90 in CBD. The occurrence of low orexin
      levels (<or=110pg/ml) was rare in both PD and DLB, and orexin levels were
      significantly lower in the PSP and CBD groups compared to PD (PSP: p<0.001, CBD:
      p<0.05). Orexin levels were inversely correlated with duration of morbidity in
      PSP but not in the other conditions studied. These findings suggest that loss of
      orexin neurons or impaired orexin neurotransmission might exist as a part of the
      neurodegeneration associated with advanced PSP with long duration of morbidity.

PMID- 17005203
TI  - Preventing familial amyotrophic lateral sclerosis: is a clinical trial feasible?
AB  - OBJECTIVE: To evaluate the feasibility of a clinical trial designed to delay or
      prevent the onset of disease amongst subjects at risk for familial amyotrophic
      lateral sclerosis (fALS). BACKGROUND: The success of many agents in prolonging
      survival in the SOD1 model of ALS has not been translated into effective
      therapies for patients with ALS. It is our hypothesis that a trial in fALS may
      reproduce the positive effects seen in fALS animals. METHODS: Pedigrees with at
      least two affected family members were constructed. Unaffected family members
      were assigned a risk status based on their relationship to affected subjects.
      Attitudes towards genetic testing were ascertained amongst the at-risk family
      members. RESULTS: We obtained data about 5,544 people (116 families) including
      516 subjects with ALS (169 from SOD1 positive families) as well as 1,056 subjects
      "definitely" or "probably" at risk for fALS (335 from SOD1 positive families). In
      excess of 80% of subjects indicated an interest in participating in a future
      clinical trial directed at delaying the onset of the disease. Assuming the use of
      a therapeutic agent that will prolong the time to the onset of fALS by 50%, we
      estimate that a sample size of between 261 and 610 subjects 'definitely at risk'
      will be required (power 0.8) depending on whether patients are followed for 10 or
      5 years respectively. CONCLUSIONS: A clinical trial in fALS may be feasible
      although such a trial would likely require prolonged follow-up and would require
      a therapeutic agent with a large clinical effect in order to be adequately
      powered.

PMID- 17005204
TI  - Differentiation of dementia with Lewy bodies from Alzheimer's disease using Mini
      Mental State Examination and brain perfusion SPECT.
AB  - To determine whether combined studies of Mini-Mental State Examination (MMSE) and
      brain single photon emission CT (SPECT) would provide more useful means of
      differentiating between dementia with Lewy bodies (DLB) and Alzheimer's disease
      (AD), we studied 36 patients with probable DLB and 96 patients with probable AD.
      DLB patients had significantly better performance on word recall, but more
      impaired attention and copying than AD patients. We confirmed that a weighted
      score derived by Ala et al. [Ala, T.A., Hughes, L.F., Kyrouac, G.A., Ghobrial,
      M.W., Elble, R.J. The Mini-Mental State exam may help in the differentiation of
      dementia with Lewy bodies and Alzheimer' disease. Int J Geriatr Psychiatry
      2002;17:503-9]: (Attention-5/3.Memory+5.Construction), was helpful in
      discriminating between DLB and AD. SPECT study revealed that medial occipital
      perfusion significantly decreased in DLB patients than AD patients. Combined
      studies of MMSE and brain SPECT achieved a high discrimination between DLB and AD
      with a sensitivity of 81% and a specificity of 85%, suggesting that there is a
      useful and practical approach to differentiate DLB from AD. Our findings will
      need to be substantiated in an independent and prospective study sample.

PMID- 17005206
TI  - Novel hybrid method for the evaluation of parameters contributing in
      determination of protein structural classes.
AB  - Due to the increasing gap between structure-determined and sequenced proteins,
      prediction of protein structural classes has been an important problem. It is
      very important to use efficient sequential parameters for developing class
      predictors because of the close sequence-structure relationship. The multinomial
      logistic regression model was used for the first time to evaluate the
      contribution of sequence parameters in determining the protein structural class.
      An in-house program generated parameters including single amino acid and all
      dipeptide composition frequencies. Then, the most effective parameters were
      selected by a multinomial logistic regression. Selected variables in the
      multinomial logistic model were Valine among single amino acid composition
      frequencies and Ala-Gly, Cys-Arg, Asp-Cys, Glu-Tyr, Gly-Glu, His-Tyr, Lys-Lys,
      Leu-Asp, Leu-Arg, Pro-Cys, Gln-Met, Gln-Thr, Ser-Trp, Val-Asn and Trp-Asn among
      dipeptide composition frequencies. Also a neural network model was constructed
      and fed by the parameters selected by multinomial logistic regression to build a
      hybrid predictor. In this study, self-consistency and jackknife tests on a
      database constructed by Zhou [1998. An intriguing controversy over protein
      structural class prediction. J. Protein Chem. 17(8), 729-738] containing 498
      proteins are used to verify the performance of this hybrid method, and are
      compared with some of prior works. The results showed that our two-stage hybrid
      model approach is very promising and may play a complementary role to the
      existing powerful approaches.

PMID- 17005207
TI  - Modeling the onset of virulence in a pectinolytic bacterium.
AB  - Building up from experimental knowledge of the regulatory network of the pel
      genes in the bacteria E. chrysanthemi, we propose for the first time a
      qualitative modeling of the infectious transition of this bacteria when it is
      hosted in a plant. We show that this infectious transition can be understood as
      the excitable dynamics of a metabolico-genetic network. Our mathematical model
      can account for the main phases which are observed in the onset of the
      pathogenecity by Erwinia chrysanthemi, namely the silent, latent and virulent
      stages. Like in many infectious agents, the silent state corresponds to the
      growth phase of the bacteria, where they multiply without significantly producing
      molecules which could trigger a counter attack of the invaded host. The latent
      stage is characterized by a moderate but unequivocal expression of the virulence
      gene, waiting for a number of conditions which have to fulfill in order to
      trigger a fully developed infection. In the virulent state the bacteria
      synthesize a massive production of virulence factors including pectate lyases
      (Pel) which favor the invasion of the host plant tissues. Our model is able to
      show cases of transitions from the silent to the virulent stages of the
      infection, using the method of the piecewise-affine (PA) differential equations
      and its implementation in the genetic network analyser software (GNA). The
      obtained qualitative dynamics of the models are consistent with the current
      experimental data about this system. Moreover it can be interpreted with respect
      to the relatively complex structure of the binding sites of pel. From the
      biological point of view, our simulations validate the picture that the promoter
      of pel has evolved to form a security device preventing a hastened expression of
      these virulent genes. This first modeling of the regulation of pel genes opens
      the way to new confrontations between theoretical ideas with experiments and
      possible strategies to fight the soft-rot disease of plants.

PMID- 17005205
TI  - Evolving therapeutic approaches to treating acute ischemic stroke.
AB  - Stroke contributes significantly to death, disability, and healthcare costs;
      however, recombinant tissue plasminogen activator (rt-PA) is the only approved
      thrombolytic therapy for acute ischemic stroke. One area of development for new
      ischemic stroke treatment options is focused on neuroprotection of viable tissue
      in the ischemic vascular bed. The ischemic penumbra is recognizable on MRI by
      decreased perfusion, in contrast to the core area of ischemia, which includes
      diffusion and perfusion abnormalities. Understanding the mechanisms of neuronal
      death, including the role of excitotoxic neurotransmitters, free radical
      production, and apoptotic pathways, is important in developing new therapies for
      stroke. This article reviews these causes and results of stroke, as well as
      current and future neuroprotective treatment options. Several compounds have
      shown neuroprotective effects in animal studies, but have failed to be effective
      in human clinical trials. Several promising therapeutic areas include targeting
      of free radicals, modulation of glutamatergic transmission, and membrane
      stabilization via ion channels.

PMID- 17005208
TI  - Esterase activities and lipid peroxidation levels in offshore commercial species
      of the NW Mediterranean Sea.
AB  - There is a lack of information on monitoring neurotoxicity in offshore commercial
      species. To help fill this gap, we sampled hake (Merluccius merluccius) and
      Norway lobster (Nephrops norvegicus) in fishing grounds off the coast of
      l'Ametlla de Mar (NW Mediterranean) in June 2005 at a depth of 100 m and 400 m.
      Additionally, at 400 m depth, two other fish species, Micromesistius poutassou
      and Phycis blennoides were included. Neurotoxicity markers such as Colinesterases
      (ChEs), namely acethyl- (AChE), butyryl- (BChE), propionyl- (PrChE) and
      carboxilesterase (CbE) were measured in muscle. Lipid peroxidation (LP), a marker
      of oxidative damage, was also included. The results are discussed in relation to
      the animal's sex, size and fishing depth. A comparison of esterases and LP levels
      between muscle and liver of hake and between muscle and hepatopancreas of Norway
      Lobster was made. AChE was dominant in muscle and CbE in hepatopancreas. No
      differences between fish species were seen for AChE. However, N. norvegicus,
      presented lower levels of ChEs and LP. A size-dependence in ChEs was seen for M.
      merluccius, with larger animals showing significantly lower activities (p<0.05).
      Sex-dependence was seen in N. norvegicus for most esterases, except AChE, with
      males displaying higher activities (p<0.05). A sampling-depth effect was also
      seen in the crustacea, with animals from 100 m generally presenting lower
      esterase activities and higher LP levels.

PMID- 17005210
TI  - A neuropsychological comparison of obsessive-compulsive disorder and
      trichotillomania.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) and trichotillomania (compulsive
      hair-pulling) share overlapping co-morbidity, familial transmission, and
      phenomenology. However, the extent to which these disorders share a common
      cognitive phenotype has yet to be elucidated using patients without confounding
      co-morbidities. AIM: To compare neurocognitive functioning in co-morbidity-free
      patients with OCD and trichotillomania, focusing on domains of learning and
      memory, executive function, affective processing, reflection-impulsivity and
      decision-making. METHOD: Twenty patients with OCD, 20 patients with
      trichotillomania, and 20 matched controls undertook neuropsychological assessment
      after meeting stringent inclusion criteria. RESULTS: Groups were matched for age,
      education, verbal IQ, and gender. The OCD and trichotillomania groups were
      impaired on spatial working memory. Only OCD patients showed additional
      impairments on executive planning and visual pattern recognition memory, and
      missed more responses to sad target words than other groups on an affective go/no
      go task. Furthermore, OCD patients failed to modulate their behaviour between
      conditions on the reflection-impulsivity test, suggestive of cognitive
      inflexibility. Both clinical groups showed intact decision-making and
      probabilistic reversal learning. CONCLUSIONS: OCD and trichotillomania shared
      overlapping spatial working memory problems, but neuropsychological dysfunction
      in OCD spanned additional domains that were intact in trichotillomania. Findings
      are discussed in relation to likely fronto-striatal neural substrates and future
      research directions.

PMID- 17005211
TI  - Self-awareness and the subconscious effect of personal pronouns on word encoding:
      a magnetoencephalography (MEG) study.
AB  - The effect of personal pronouns such as "ein" (German for "a"), "mein" (German
      for "my") and "sein" (German for "his") on the processing of associated nouns was
      investigated using MEG. Three different encoding strategies were provided in
      order to vary the level of consciousness involved in verbal information
      processing. A shallow (alphabetic), a deep (semantic) and a very deep
      (contextual) encoding instruction related to visual word presentation were given
      to all study participants. After the encoding of pronoun-noun pairs, recognition
      performances of nouns only were tested. The number of correctly recognized nouns
      previously associated with "sein" was significantly lower than the number of
      correctly recognized nouns previously associated with "ein" in the shallow
      encoding condition. The same trend was found for "mein" associated nouns which
      were also less accurately recognized compared to "ein" associated nouns. Magnetic
      field distributions recorded during the encoding phases revealed two significant
      effects, one between about 200 and 400ms after stimulus onset and the other
      between about 500 and 800ms. The earlier effect was found over occipito-parietal
      sensors, whereas the later effect occurred over left frontal sensors. Within both
      time ranges, brain activation varied significantly as a function of associated
      pronoun independent of depth of word processing. In the respective areas of both
      time ranges, conditions including personal pronouns ("mein" and "sein") showed
      higher magnetic field components compared to the control condition of no personal
      pronouns ("ein"). Evidence is shown that early stage processing is able to
      distinguish between no personal and personal information, whereas later stage
      processing is able to distinguish between information related to oneself and to
      another person (self and non-self). Along with other previous reports our MEG
      findings support the notion that particular human brain functions involved in
      processing neurophysiological correlates of self and non-self can be identified.

PMID- 17005212
TI  - Thematic role assignment in patients with Broca's aphasia: sentence-picture
      matching electrified.
AB  - An event-related brain potential experiment was carried out to investigate on
      line thematic role assignment during sentence-picture matching in patients with
      Broca's aphasia. Subjects were presented with a picture that was followed by an
      auditory sentence. The sentence either matched the picture or mismatched the
      visual information depicted. Sentences differed in complexity, and ranged from
      simple active semantically irreversible sentences to passive semantically
      reversible sentences. ERPs were recorded while subjects were engaged in sentence
      picture matching. In addition, reaction time and accuracy were measured. Three
      groups of subjects were tested: Broca patients (N=10), non-aphasic patients with
      a right hemisphere (RH) lesion (N=8), and healthy aged-matched controls (N=15).
      The results of this study showed that, in neurologically unimpaired individuals,
      thematic role assignment in the context of visual information was an immediate
      process. This in contrast to patients with Broca's aphasia who demonstrated no
      signs of on-line sensitivity to the picture-sentence mismatches. The syntactic
      contribution to the thematic role assignment process seemed to be diminished
      given the reduction and even absence of P600 effects. Nevertheless, Broca
      patients showed some off-line behavioral sensitivity to the sentence-picture
      mismatches. The long response latencies of Broca's aphasics make it likely that
      off-line response strategies were used.

PMID- 17005213
TI  - Sex differences in brain control of prosody.
AB  - Affective (emotional) prosody is a neuropsychological function that encompasses
      non-verbal aspects of language that are necessary for recognizing and conveying
      emotions in communication, whereas non-affective (linguistic) prosody indicates
      whether the sentence is a question, an order or a statement. Considerable
      evidence points to a dominant role for the right hemisphere in both aspects of
      prosodic function. However, it has yet to be established whether separate parts
      of the right hemisphere are involved in processing different kinds of emotional
      intonation. The aim of this study was to answer this question. In addition, the
      issue of sex differences in the ability to understand prosody was considered.
      Fifty-two patients with damage to frontal, temporo-parietal or subcortical
      (basal) parts of the right hemisphere and 26 controls were tested for their
      ability to assess prosody information in normal (well-formed) sentences and in
      pseudo-sentences. General impairment of prosody processing was seen in all
      patient groups but the effect of damage was more apparent for emotional rather
      than linguistic prosody. Interestingly, appreciation of emotional prosody
      appeared to depend on the type of emotional expression and the location of the
      brain lesion. The patients with frontal damage were mostly impaired in
      comprehension of happy intonations; those with temporo-parietal damage in
      assessment of sad intonations, while subcortical lesions mostly affected
      comprehension of angry intonations. Differential effects of lesion location on
      the performance of men and women were also observed. Frontal lesions were more
      detrimental to women, whereas subcortical lesions led to stronger impairment in
      men. This suggests sex differences in brain organization of prosodic functions.

PMID- 17005214
TI  - Memory and the Korsakoff syndrome: not remembering what is remembered.
AB  - Following the distinction between involuntary unconscious memory, involuntary
      conscious memory, and intentional retrieval, the focus of the present paper is
      whether there is an impairment of involuntary conscious memory among Korsakoff
      patients. At study, participants generated associations versus counted the number
      of letters with enclosed spaces or the number of vowels in the target words
      (semantic versus perceptual processing). In the Direct tests, stems were to be
      used to retrieve the targets with either guessing or no guessing allowed; in the
      Opposition tests, the stems were to be completed with the first word that came to
      mind but using another word if that first word was a target word; and in the
      Indirect tests, no reference was made to the target words from the study phase.
      In the Direct tests, the performance of Korsakoff patients was not necessarily
      worse than the one of healthy controls, provided guessing was allowed. More
      critical for the Korsakoff patients was the deficient involuntary conscious
      memory. The deficiency explained the suppression failures in the Opposition
      tests, the absence of performance differences between the Indirect and Opposition
      tests, the absence of a beneficial effect in providing information about the
      status of the stem, the performance boost when allowed to guess, and the very low
      rate of "Know"/"Remember" responses.

PMID- 17005215
TI  - Oral hydration, parotid salivation and the perceived pleasantness of small water
      volumes.
AB  - Previous studies have suggested that the preference for drinking cold water is
      increased when the drinker has a dry mouth. In a first experiment, we
      investigated whether a positive shift in preference would occur for small water
      volumes (0.75 ml and 1.5 ml) at 8, 16 or 25 degrees C, delivered into a mouth
      that had been dried using a warmed airflow, versus a normally hydrated mouth.
      Subjects rated the perceived wetness (or dryness) of their mouth, and the
      perceived pleasantness (or unpleasantness) of the water samples, using a labeled
      magnitude scale. Cooler water samples were preferred, and consistent with
      previous research, this preference was slightly enhanced when the subject's mouth
      was dried. The coldest water sample led to significantly wetter mouthfeel than
      the other two less cold samples, consistent with the possibility that the coldest
      water increased the rate of salivation. However, a second experiment found that
      although the rate of parotid salivation was increased if the mouth had been dried
      using a warm airflow, the different water temperatures did not induce different
      rates of parotid salivation. This indicates that enhanced preference for cold
      water when the mouth is dry is not invariably based in the reward gained from
      mouth rewetting via increased parotid saliva flow.

PMID- 17005216
TI  - The crystal structure of Arabidopsis thaliana RAC7/ROP9: the first RAS
      superfamily GTPase from the plant kingdom.
AB  - Arabidopsis thaliana RAC/ROP GTPases constitute a plant specific Rho GTPase
      family in the RAS superfamily, which has been implicated in numerous pivotal
      signalling cascades in plants. Research has shown that plants in some cases have
      evolved different modes of regulating Rho GTPase activity as compared to the
      equivalent systems in animals and yeast. In order to gain structural insight into
      plant signaling at the molecular level, we have determined the first crystal
      structure of a RAC-like GTPase belonging to the RAS superfamily from the plant
      kingdom. The structure of AtRAC7/ROP9 bound to GDP was solved at a resolution of
      1.78 A. We have found that the structure of plant Rho GTPases is based upon a
      conserved G-domain architecture, but structural differences were found concerning
      the insert region and switch II region of the protein.

PMID- 17005217
TI  - Factors affecting tooth loss among rural Khon Kaen adults: analysis of two data
      sets.
AB  - BACKGROUND: Tooth loss is an oral health problem affecting Thai people and people
      of other nations as well. Not much of epidemiologic evidence concerning factors
      affecting tooth loss among Thai people has been reported although severity of
      tooth loss among Thai people has never been decreased. METHODS: This study
      employed two existing data sets to evaluate the role of health behaviors such as
      tobacco smoking and betel quid chewing (a common habit prevalent among rural Thai
      females), together with other factors in relation to tooth loss among rural Thai
      people. The study population in the first (phase I) and second (phase II) data
      sets included 1484 and 3471 male and female adults residing in rural areas of
      Khon Kaen province, Thailand during 1990-1991 and 1992-1994, respectively. The
      data were obtained through oral examination and interview. Employing descriptive,
      bivariate, and multivariable Poisson regression, key risk indicators of tooth
      loss were identified for both data sets. RESULTS: The findings from final
      multivariable Poisson regression models were consistent in that tobacco smoking,
      betel quid chewing, age, dental caries (defined as decayed plus filled teeth) and
      periodontitis were significantly related to tooth loss among these rural
      populations. CONCLUSION: Therefore, preventive programs aiming at discouraging
      Thai people from smoking tobacco and/or chewing betel quid should be established
      so that healthy natural teeth can be maintained.

PMID- 17005218
TI  - Action on cycling in primary care trusts: results of a survey of Directors of
      Public Health.
AB  - BACKGROUND: Cycling is a form of physical activity with the potential to make a
      significant contribution to improving public health; however, participation
      levels are decreasing. Primary-care trusts (PCTs) are in a position to influence
      local provision for cycling but the extent of their involvement in policy and
      practice on cycling is unknown. A survey of Directors of Public Health in PCTs
      was conducted to establish the level and type of PCT involvement in policies,
      strategies, programmes and projects on cycling. METHODS: Directors of Public
      Health on the Faculty of Public Health database were sent an e-mail inviting them
      to complete an online questionnaire that addressed key issues of PCT involvement
      with cycling. RESULTS: One hundred and sixty-five responses were received (49% of
      all PCTs). Thirty-two per cent of respondents said there was someone in the PCT
      with specific responsibility for cycling. Less than half of PCTs had the basic
      facilities to encourage staff or visitors to cycle to their premises. Around one
      in 10 said that cycling was included in their travel plan or local delivery plan,
      and 49% of respondents said that their physical activity strategy contained
      reference to cycling. Joint working on the local strategic partnership and
      community plan was common, with 94% and 82% of PCTs, respectively, saying they
      had worked with other agencies on these plans. Most PCTs (60%) had worked on the
      Local Transport Plan. Specific knowledge of cycling policy was low, and demand
      for additional resources high. CONCLUSION: Cycling does not seem to be high on
      PCTs' agendas, despite its great potential to improve public health. More could
      be done to ensure that cycling is given a far greater emphasis within the work of
      PCTs, notably PCT input into local transport plan development, and production of
      local physical activity strategies.

PMID- 17005219
TI  - Seroepidemiological study of viral hepatitis among workers of the Cleaning
      Department of the Municipality of Vyronas: Preliminary results of a single centre
      study.

PMID- 17005220
TI  - Introducing Vi polysaccharide typhoid fever vaccine to primary school children in
      North Jakarta, Indonesia, via an existent school-based vaccination platform.
AB  - OBJECTIVES: To report results on coverage, safety and logistics of a large-scale,
      school-based Vi polysaccharide immunization campaign in North Jakarta. METHODS:
      Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were
      randomly selected for this study. Exclusion criteria were fever 37.5 degrees C or
      higher at the time of vaccination or a known history of hypersensitivity to any
      vaccine. Adverse events were monitored and recorded for 1 month after
      immunization. Because this was a pilot programme, resource use was tracked in
      detail. RESULTS: During the February 2004 vaccination campaign, 4828 students
      were immunized (91% of the target population); another 394 students (7%) were
      vaccinated during mop-up programmes. Informed consent was obtained for 98% of the
      target population. In all, 34 adverse events were reported, corresponding to
      seven events per 1000 doses injected; none was serious. The manufacturer
      recommended cold chain was maintained throughout the programme. CONCLUSIONS: This
      demonstration project in two sub-districts of North Jakarta shows that a large
      scale, school-based typhoid fever Vi polysaccharide vaccination campaign is
      logistically feasible, safe and minimally disruptive to regular school
      activities, when used in the context of an existing successful immunization
      platform. The project had high parental acceptance. Nonetheless, policy-relevant
      questions still need to be answered before implementing a widespread Vi
      polysaccharide vaccine programme in Indonesia.

PMID- 17005221
TI  - Confirmation of sex-specific transcripts from Ancylostoma caninum adult worms by
      semi-quantitative RT-PCR.
AB  - In a previous work Ancylostoma caninum sex-specific genes had being identified,
      however without confirmation, by using an non specific RT-PCR comparing male and
      female cDNA. In this work more fragments had been identified and a semi
      quantitative RT-PCR carried out in order to confirm the sex-specific character of
      the transcripts obtained. Four fragments were confirmed as sex-specific or as
      being expressed more in one sex than the other.

PMID- 17005222
TI  - A randomised trial to assess the safety and efficacy of artemether-lumefantrine
      (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in
      Rwanda.
AB  - Coartem is a fixed-dose combination of artemether-lumefantrine that, given in six
      doses, provides effective treatment for children with uncomplicated Plasmodium
      falciparum infection in areas with highly endemic and multidrug-resistant
      malaria. In Rwanda since 2001, amodiaquine+sulfadoxine-pyrimethamine (AQ+SP) has
      been the first-line treatment, but resistance to this combination has rapidly
      emerged and spread. Coartem was considered as a possible alternative, and a
      randomised, open-label, clinical trial to test its safety, tolerability and
      efficacy was carried out in 2004-2005. Five hundred children aged 12-59 months
      with uncomplicated P. falciparum malaria were randomly allocated to AQ+SP or
      Coartem. Patients were followed up until day 28 after treatment. Adverse events
      and clinical and parasitological outcomes were recorded. Adequate clinical and
      parasitological response (ACPR) was significantly higher in children treated with
      Coartem than in those treated with AQ+SP: the PCR-adjusted 28-day ACPR was 96.68%
      for Coartem and 79.35% for AQ+SP. Both treatments rapidly cleared parasitaemia
      and fever, although parasite clearance was significantly faster in children
      treated with Coartem. Mean packed cell volume increased in all patients, with no
      significant differences between treatments. Coartem proved to be more efficacious
      than AQ+SP, with a good safety and tolerability profile.

PMID- 17005223
TI  - Ultrastructure of the sperm of blue sprat, Spratelloides gracilis; Teleostei,
      Clupeiformes, Clupeidae.
AB  - The general sperm structure of the investigated clupeoids possess an oliviform
      head with a distinct deep nuclear fossa, a midpiece with one mitochondrion and a
      posterior flagellum. They are characterized by two apomorphies: an annular or C
      shaped mitochondrion and ITDs (intratubular differentiation) in the A tubules of
      the axonemal doublets. The fine structure of the spermatozoa of blue sprat,
      Spratelloides gracilis, was investigated to see if resulting data conformed to
      the current hypotheses of the taxonomy of the Clupeidae. The mature sperm is
      characterized by the following features: (1) the nucleus is oliviform; its
      prominent deep nuclear fossa encloses the initial portion of flagellum, (2) a
      proximal centriole has not been identified, (3) a single spherical mitochondrion
      is located laterally in relation to the flagellum and (4) no cytoplasmic canal is
      present. Our blue sprat-spermatozoan morphology data suggest that the blue sprat
      has Clupeomorpha affinities, while indicating no close affinity with Elopomorpha.
      Clupeoid sperm exhibit morphological variations with the nucleus and
      mitochondrion being particularly variable. This study provides useful systematic
      characters to the existing knowledge of comparative spermatology and may provide
      additional clue to Euteleost phylogeny.

PMID- 17005224
TI  - Induction of cyclin D1 by submicromolar concentrations of arsenite in human
      epidermal keratinocytes.
AB  - Arsenic is a prevalent environmental carcinogen but arsenic is not directly
      mutagenic and the mechanism by which arsenite brings about oncogenic
      transformation is poorly understood. To gain insight into the oncogenic
      properties of arsenic, we studied the expression of cyclin D1 in cultured human
      epidermal keratinocytes treated with submicromolar concentrations of sodium
      arsenite. Arsenite at concentrations between 200 and 800 nM over a 3-day period
      brought about an increase in cell growth rate. Uptake of the vital stain, neutral
      red, arsenite at 200 and 400 nM concentrations brought about a parallel increase
      in cell viability over the same treatment period. Analysis of cell cycle
      parameters by flow cytometry showed that the growth stimulation was accompanied
      by a concomitant shift from the G1 into the S/G2 cell cycle compartment in the
      arsenite-treated cells. Real-time PCR analysis of cyclin D1 transcription showed
      that there was an induction of more than three-fold in cells exposed to 400 nM
      arsenite for 3 days. Quantitation of cyclin D levels in Western blots showed that
      arsenite treatment caused a time-dependent induction of cyclin D proteins
      representing an induction of about 2.0-fold after a 7 day treatment period.
      Electrophoretic mobility shift assays (EMSA) showed that arsenite also stimulated
      binding of the transcription factors, AP1 and CREBP to their respective binding
      motifs within 3 days. This supports a mechanism of oncogenesis based on
      persistent upregulation of D type cyclins leading to a concomitant loss of G1/S
      checkpoint control.

PMID- 17005226
TI  - Microcystins cause embryonic toxicity in mice.
AB  - Microcystins produced by freshwater cyanobacteria are potent hepatotoxins and can
      cause animal intoxications and human illnesses. In the present study, the effects
      of microcystins on the embryonic development of Kunming mice were determined
      using cell extracts of Microcystis aeruginosa from the Nanwan reservoir, China.
      Forty-eight pregnant mice were divided into four groups of 12 mice. Pregnant mice
      in three experimental groups were injected intraperitoneally with cell extracts
      at doses equivalent to 3, 6, or 12 microg microcystins/kg body weight daily from
      gestational days 6-15, while the mice in the control group were injected on the
      same schedule with sterilized saline. Mice were killed on the 18th day of
      gestation and embryonic and fetal developmental indexes checked. The fetal mice
      were also examined for anomalies of external, skeletal, and internal organs. The
      results demonstrated a significant decrease in body weight gain of pregnant mice
      in the 12 microg/kg dose group when compared to the control group (p<0.05).
      Differences in mean body weight, body length, and tail length of the fetuses were
      also found in these two groups (p<0.05). However, no significant difference in
      these characteristics was detected in the 6 or 3 microg/kg dose groups when
      compared to the control group (p>0.05). Four fetuses in the 6 microg/kg body dose
      group were found to have a curving tail. Additionally, petechial hemorrhage and
      hydropic degeneration were observed in the livers of fetuses in the 6 and 12
      microg/kg experimental groups. These results suggested that microcystins had both
      maternal and embryonic toxicity in mice.

PMID- 17005225
TI  - T-2 toxin impairs murine immune response to respiratory reovirus and exacerbates
      viral bronchiolitis.
AB  - Exposure to immunosuppressive environmental contaminants is a possible
      contributing factor to increased occurrence of viral respiratory diseases. The
      objective of this study was to test the hypothesis that the trichothecene
      mycotoxin T-2 toxin (T-2), a frequent food contaminant, alters host resistance to
      lung infection by reovirus, a model respiratory virus. Balb/c mice (4 week old)
      were treated intraperitoneally with T-2 toxin (1.75 mg/kg bw) or saline vehicle
      and then intranasally instilled 2 h later with 10(7) plaque forming unit (PFU) of
      reovirus, strain Lang (T1/L) or saline vehicle. At 10 days post-instillation
      (PI), both virus plaque-forming responses and reovirus L2 gene expression were 10
      fold higher in lungs of T-2-treated mice compared to controls. No-effect and
      lowest-effect levels for T-2-induced suppression of reovirus clearance were 20
      and 200 microg/kg bw, respectively. Respiratory reovirus infection resulted in a
      mild bronchiolitis with minimal alveolitis, which was markedly exacerbated by T-2
      pretreatment. Reovirus exposure induced marked increases in total cells,
      neutrophils and lymphocytes at 3 and 7 days PI in bronchial alveolar lavage fluid
      (BALF) whereas macrophages were increased only at 7 days PI. Although prior T-2
      exposure attenuated total cell and macrophage counts in BALF of control and
      infected mice at 3 days PI, the toxin potentiated total cell, macrophage,
      neutrophil and lymphocyte counts in infected mice at 7 days PI. At 3 days PI, T-2
      suppressed reovirus-induced IFN-gamma elevation in BALF, but enhanced production
      of IL-6 and MCP-1. T-2 pretreatment also suppressed reovirus-specific mucosal IgA
      responses in lung and enteric tract, but potentiated serum IgA and IgG responses.
      Taken together, T-2 increased lung viral burden, bronchopneumonia and pulmonary
      cellular infiltration in reovirus-infected mice. These effects might be
      attributable to reduced alveolar macrophage levels as well as modulated cytokine
      and mucosal Ig responses.

PMID- 17005227
TI  - Multi-parameter ultrasound transmission tomography of biological media.
AB  - Using a specially elaborated computer software and research setup, within the
      scope of this paper, projection and tomographic calculations (simulation) and
      real measurements of biological media by means of ultrasound were carried out,
      and the images of different parameters of the ultrasonic wave run through
      biological objects were obtained. The images were analyzed from the point of view
      of the precision of representation of the structures and visualization of
      different features of these structures. On the basis of the results obtained it
      can be said that such a complex multi-parameter ultrasound transmission
      tomography (MUTT) is best suited for diagnosing early stages of tumors in
      tissues, and especially women's breast tumors, because of the structure of this
      organ and its possible scanning in vivo from many directions.

PMID- 17005228
TI  - Image-based sizing of surface-breaking cracks by SH-wave array ultrasonic
      testing.
AB  - This paper presents calibration-free crack sizing techniques based on ultrasonic
      imaging. The techniques are intended for 2D (line) surface-breaking cracks with
      the size of the incident wavelength or greater. The probing wave mode is the anti
      plane shear wave (SH-wave). Two methods are employed for the ultrasonic imaging.
      One is a synthetic aperture focusing technique (SAFT) and the other is a computed
      time-reversal focusing technique (TRFT). In this paper, those methods are
      modified so that crack tips are located directly from measured A-scope waveforms
      without any calibration experiments. The results are shown as a peak in the
      ultrasonic image created by the respective methods. Reasonable accuracies of the
      proposed techniques are demonstrated first for the sizing of slits with known
      depths. The techniques are applied thereafter to the sizing of fatigue cracks.
      Since fatigue cracks may not be open without an external load, ultrasonic
      measurements are taken with and without external loads. The results of the
      imaging show that the depths of open cracks can be estimated accurately. It is
      also shown that crack opening (closing) behavior can be deduced by observing
      appearance (disappearance) of the peak in the images indicating the crack tip.

PMID- 17005229
TI  - Effects of alcohols on multi-bubble sonoluminescence spectra.
AB  - Spectra of multi-bubble sonoluminescence (MBSL) were measured in argon-saturated
      water and ethanol solutions in the concentration range 2-100 mM at the
      frequencies of 116 kHz and 1.0 MHz. The spectral peaks from OH-radical emission
      near 310 nm were observed at relatively low ultrasonic power at both frequencies.
      The sub-peaks at 290 and 340 nm were also observed, which are attributed to OH
      radical vibronic transition. The MBSL spectra from ethanol solutions indicated
      that the quenching of OH-radical emission was more efficient than that of
      underlying continuous spectrum. The continuous spectrum suggested the decrease in
      temperature with increasing ethanol concentration. The concentration dependence
      of spectrum quenching showed no frequency dependence. A new peak was observed at
      385 nm only at small ethanol concentrations and at the frequency of 1.0 MHz,
      which attributed to CH or CN molecule emission.

PMID- 17005230
TI  - Protein composition of the vaccinia virus mature virion.
AB  - The protein content of vaccinia virus mature virions, purified by rate zonal and
      isopycnic centrifugations and solubilized by SDS or a solution of urea and
      thiourea, was determined by the accurate mass and time tag technology which uses
      both tandem mass spectrometry and Fourier transform-ion cyclotron resonance mass
      spectrometry to detect tryptic peptides separated by high-resolution liquid
      chromatography. Eighty vaccinia virus-encoded proteins representing 37% of the
      218 genes annotated in the complete genome sequence were detected in at least
      three analyses. Ten proteins accounted for approximately 80% of the virion mass.
      Thirteen identified proteins were not previously reported as components of
      virions. On the other hand, 8 previously described virion proteins were not
      detected here, presumably due to technical reasons including small size and
      hydrophobicity. In addition to vaccinia virus-encoded proteins, 24 host proteins
      omitting isoforms were detected. The most abundant of these were cytoskeletal
      proteins, heat shock proteins and proteins involved in translation.

PMID- 17005231
TI  - Real-world visual search is dominated by top-down guidance.
AB  - How do bottom-up and top-down guidance signals combine to guide search behavior?
      Observers searched for a target either with or without a preview (top-down
      manipulation) or a color singleton (bottom-up manipulation) among the display
      objects. With a preview, reaction times were faster and more initial eye
      movements were guided to the target; the singleton failed to attract initial
      saccades under these conditions. Only in the absence of a preview did subjects
      preferentially fixate the color singleton. We conclude that the search for
      realistic objects is guided primarily by top-down control. Implications for
      saliency map models of visual search are discussed.

PMID- 17005233
TI  - The continuous Wagon Wheel Illusion is object-based.
AB  - The occurrence of perceived reversed motion while observers view a periodic,
      continuously moving stimulus (the "continuous Wagon Wheel Illusion") has been
      taken as evidence that some aspects of motion perception rely on discrete
      sampling of visual information. The spatial extent of this sampling is currently
      under debate. When two separate motion stimuli are viewed simultaneously, the
      illusion of reversed motion rarely occurs for both objects together: this rules
      out global sampling of the visual field. The same result holds when the objects
      are superimposed by transparency: this argues against location-based sampling.
      Here we show that the sampling is in fact object-based: we use a rotating ring
      stimulus split in two halves. When the two halves move in opposite directions,
      appearing to belong to separate objects, perceptual reversals occur in either
      half at a time, but rarely in both. When the two halves physically move in
      compatible directions, they generally appear to reverse simultaneously: the
      illusion keeps the perceptual object united. Rather than the local low-level
      properties of the motion stimulus (which are comparable in both cases), it is
      thus the high-level organization of the scene that determines the extent of
      perceived motion reversals. These results imply that the continuous Wagon Wheel
      Illusion, and any discrete perceptual sampling that may cause it, is restricted
      to the object of our attention.

PMID- 17005232
TI  - Oligomeric structure of the alpha1b-adrenoceptor: comparisons with rhodopsin.
AB  - The structural basis of the quaternary organization of rhodopsin has recently
      been explored and modeled. Because information obtained from studying rhodopsin
      has frequently been directly applicable to other G protein-coupled receptors we
      wished to ascertain if dimeric and/or oligomeric forms of the alpha(1b)
      adrenoceptor could be observed and if so whether rhodopsin might provide insights
      into the quaternary structure of this receptor. Co-immunoprecipitation and both
      conventional and time-resolved fluorescence resonance energy transfer studies
      demonstrated quaternary structure of the alpha(1b)-adrenoceptor and, in concert
      with the reconstitution of fragments of this receptor, provided information on
      the molecular basis of these interactions. Development of three color
      fluorescence resonance energy transfer (FRET) allowed the imaging of alpha(1b)
      adrenoceptor oligomers in single living cells. Mutation of hydrophobic residues
      in transmembrane domains I and IV of the receptor resulted in marked reduction in
      three color FRET suggesting an alteration in oligomeric organization and
      potential similarities with rhodopsin. The mutated alpha(1b)-adrenoceptor was
      unable to reach the cell surface, did not become terminally N-glycosylated and
      was unable to signal.

PMID- 17005234
TI  - Retrospective monitoring of organotin compounds in freshwater fish from 1988 to
      2003: results from the German environmental specimen bank.
AB  - In archived samples from the German environmental specimen bank (ESB) organotin
      compounds including tributyltin (TBT) and triphenyltin (TPT) as well as their
      potential degradation products were quantified. Muscles of bream (Abramis brama)
      sampled in the period 1993-2003 from the rivers Rhine, Elbe, Saale, Mulde, Saar,
      and from Lake Belau (period 1988-2003) were analyzed by gas chromatography/atomic
      emission detection-coupling after extraction and derivatization. TBT was detected
      in nearly all samples and a decrease in levels was observed at all sampling
      sites. At most sites, the reduction seemed to be a result of the ban on the use
      of TBT-based antifoulants for the application on small boats, which became
      effective in Germany in 1989. Highest TBT levels were found in fish from the Elbe
      near Blankenese (470 ng TBT cation per g fresh weight; in 1995) and lowest in
      bream from Lake Belau (<1 ngg(-1); in 2001 and 2003). Highest TPT levels (253
      ngg(-1) in 1993) were also found in bream caught near Blankenese where the
      occurrence seemed to be correlated to the former use of TPT as co-toxicant in
      antifoulants. At other sites TPT levels seemed to be correlated to its use as
      fungicide (e.g. 9 +/- 2 ngg(-1) in bream from Lake Belau in 2001).

PMID- 17005235
TI  - Effects of potassium alkalis and sodium alkalis on the dechlorination of o
      chlorophenol in supercritical water.
AB  - Effects of potassium alkalis and sodium alkalis on the dechlorination of o
      chlorophenol (o-CP) in supercritical water (SCW) were studied in this paper under
      the conditions of 450 degrees C and 25 MPa. Experimental results indicated that
      the dechlorination of o-CP can be accelerated significantly by all alkalis
      investigated. The dechlorination of o-CP proceeded mainly via two pathways:
      hydrodechlorination and hydrolysis. Both of the two pathways can be promoted by
      alkalis, and the dechlorination of o-CP can be accelerated by both the cations
      and hydroxide ion dissociated from alkalis. The overall dechlorination of o-CP
      can be accelerated by cations via promoting the hydrodechlorination pathway,
      while, hydroxide ion via promoting the hydrolysis pathway. In addition, the
      hydrodechlorination can be accelerated faster by sodium alkalis than that by
      potassium ones, while, the hydrolysis can be promoted faster by potassium
      alkalis. This difference may be caused by the different charge density between
      potassium ion and sodium ion, and the different solubility and dissociation
      constant between potassium alkalis and sodium alkalis in SCW. Dechlorination of o
      CP with addition of alkalis prior to supercritical water oxidation (SCWO) process
      not only can avoid the reactor corrosion caused by the generated hydrochloric
      acid in direct SCWO of o-CP, but also can reduce the formation of toxic
      chlorinated byproducts compared with direct SCWO process or SCWO of o-CP with
      addition of alkali.

PMID- 17005236
TI  - Lower variability of radionuclide activities in upland dairy products compared to
      soils and vegetation: implication for environmental survey.
AB  - Contamination of the environment by radionuclides is usually estimated using soil
      and grass sampling. However, radionuclides are often not homogeneously
      distributed in soils. In the alpine Mercantour region (Western Alps, France) a
      large heterogeneity in Chernobyl 137Cs deposition has been previously observed.
      Here we report additional 137Cs results together with new 90Sr and Pu data for
      soil, grass, milk, and cheese samples. The results show that radioisotopes from
      nuclear weapons tests fallout are more homogeneously distributed than Chernobyl
      137Cs. Further, we observe that the 137Cs and 90Sr contents are less variable in
      milk samples than in grass or soil samples. This can be attributed to the
      homogenization effect of cow vagrancy during grazing. Hence milk seems to be a
      more robust sample than soil or grass to evaluate the extent of contamination on
      a regional scale. We explore this idea by comparing own unpublished 90Sr results
      and 90Sr results from the literature to establish the relationship between
      altitude of grazing and contamination of soil and milk for Western Europe. There
      is a significant positive correlation between soil contamination and altitude and
      an even closer correlation between milk 90Sr activity (A) and altitude (h): A =
      A0 + e(k x h) where A0 is the expected activity of milk sampled at sea level (A0
      = 0.064 +/- 0.014 Bq g(-1) Ca) and h is the altitude of grazing, k being a
      constant (k = 0.95 x 10(-3) +/- 0.11 x 10(-3) m(-1) Bq g(-1) Ca). The fact that
      there is less scattering in the relationship for the 90Sr(milk)-altitude than for
      90Sr(soil)-altitude suggests, again, that milk is a well-suited sample for
      environmental survey. The relationship between the altitude of grazing and the
      90Sr content of milk and cheese can also be used to assess the authenticity of
      dairy products.

PMID- 17005237
TI  - Reduced analytical availability of polychlorinated biphenyls (PCB's) in colored
      surface water.
AB  - It has been generally accepted, during the last few decades, that the dissolved
      natural organic matter in water [DNOM] appearing as yellow brownish color, has
      become more and more "polluted" by inorganic and organic micro-pollutants. Due to
      the complexing properties of NOM, lipophilic organic micro-pollutants, such as,
      PCBs will be mobilized into water together with the DNOM. A mixture of eight
      PCBs, with Cl-content from tri-Cl to hepta-Cl, was added to solutions of ten
      different DNOMs. The DNOMs were aqua's solutions of RO-(reverse osmosis)-isolated
      material, having approximately the same concentration of carbon. After a contact
      time of three days, standard analytical PCB-method was used to determine the
      recovery of the added PCBs. The results show that the analytical availability of
      the added PCB was significantly reduced in the presence DNOM, compared to
      distilled water. The percentage loss in recovery of PCB increased with the
      content of Cl, in mean, from 3%/mg C for tri-Cl to 9%/mg C for hepta-Cl. The
      results also suggest that the analytical recovery of PCB was affected by the
      quality and the nature of the organic matter. For example the longer the DNOMs
      had been in the aquatic phase, the less efficient they are attached to the PCBs.

PMID- 17005238
TI  - Biodegradation rates of 2-methylisoborneol (MIB) and geosmin through sand filters
      and in bioreactors.
AB  - Taste and odour (T&O) causing compounds, in particular, 2-methylisoborneol (MIB)
      and geosmin, are a problem for water authorities as they are recalcitrant to
      conventional water treatment. In this study, biological sand filtration was shown
      to be an effective process for the complete removal of MIB and geosmin, with
      removal shown to be predominantly through biodegradation. In addition, MIB and
      geosmin were also effectively degraded in batch bioreactor experiments using
      biofilm sourced from one of the sand filters as the microbial inoculum. The
      biodegradation of MIB and geosmin was determined to be a pseudo-first-order
      reaction with rate constants ranging between 0.10 and 0.58 d(-1) in the
      bioreactor experiments. Rate constants were shown to be dependent upon the
      initial concentration of the microbial inoculum but not the initial concentration
      of MIB and geosmin when target concentrations of 200 and 50 ng l(-1) were used.
      Furthermore, rate constants were shown to increase upon re-exposure of the
      biofilm to both T&O compounds. Enrichment cultures with subsequent community
      profile analysis using 16S rRNA-directed PCR-DGGE identified four bacteria most
      likely involved in the biodegradation of geosmin within the sand filters and
      bioreactors. These included a Pseudomonas sp., Alphaproteobacterium, Sphingomonas
      sp. and an Acidobacteriaceae member.

PMID- 17005239
TI  - Heavy metal fates in laboratory bioretention systems.
AB  - Key to managing heavy metals in bioretention is to understand their fates in
      bioretention facilities. In this study, pot prototypes filled with bioretention
      media were built to simulate the conditions of natural growth of plants.
      Synthetic runoff with different heavy metal loadings (copper, cadmium, lead, and
      zinc) was periodically applied. Metal accumulations in tissues of grasses 
      Panicum virgatum, Kentucky-31, and Bromus ciliatus, were investigated after 230d
      of growth and multiple runoff treatment events. After 183d of periodic runoff
      application, the concentrations of Zn, Cu, Pb and Cd with low and high loadings
      had the same trends in the plant tissues, Zn>Cu>Pb>Cd, following the trend of the
      input metal concentrations. The fates of input metals were 88-97% captured in
      soil media, 2.0-11.6% not captured by bioretention media, and 0.5-3.3%
      accumulated in plants. Compared to the metals retained by the soil, the
      percentages of input metals taken up by plants were relatively low due to the low
      plant biomass produced in this study. Greater biomass density would be required
      for the vegetation to have a valuable impact in prolonging the lifetime of a
      bioretention cell.

PMID- 17005240
TI  - Influence of watershed system management on herbicide concentrations in
      Mississippi Delta oxbow lakes.
AB  - The Mississippi Delta Management Systems Evaluation Area (MD-MSEA) project was
      established in 1994 in three small watersheds (202 to 1,497 ha) that drain into
      oxbow lakes (Beasley, Deep Hollow, and Thighman). The primary research objective
      was to assess the implications of management practices on water quality. Monthly
      monitoring of herbicide concentrations in lake water was conducted from 2000 to
      2003. Water samples were analyzed for atrazine, cyanazine, fluometuron,
      metolachlor, and atrazine metabolites. Herbicide concentrations observed in the
      lake water reflected cropping systems of the watershed, e.g., atrazine and
      metolachlor concentrations were associated with the level of corn and sorghum
      production, whereas cyanazine and fluometuron was associated with the level of
      glyphosate-sensitive cotton production. The dynamics of herbicide appearance and
      dissipation in lake samples were strongly influenced by herbicide use, lake
      hydrology, rainfall pattern, and land management practices. The highest maximum
      concentrations of atrazine (7.1 to 23.4 microg L(-1)) and metolachlor (0.7 to
      14.9 microg L(-1)) were observed in Thighman Lake where significant quantities of
      corn were grown. Introduction of s-metolachlor and use of glyphosate-resistant
      cotton coincided with reduced concentration of metolachlor in lake water.
      Cyanazine was observed in two lakes with the highest levels (1.6 to 5.5 microg L(
      1)) in 2000 and lower concentrations in 2001 and 2002 (<0.4 microg L(-1)).
      Reduced concentrations of fluometuron in Beasley Lake were associated with
      greater use of glyphosate-resistant cotton and correspondingly less need for soil
      applied fluometuron herbicide. In contrast, increased levels of fluometuron were
      observed in lake water after Deep Hollow was converted from conservation tillage
      to conventional tillage, presumably due to greater runoff associated with
      conventional tillage. These studies indicate that herbicide concentrations
      observed in these three watersheds were related to crop and soil management
      practices.

PMID- 17005241
TI  - Measurements of endotoxin on ambient loaded PM filters after long-term storage.
AB  - At present there exist unsolved questions, whether endotoxin measurements on PM
      filters show valid measurements after long-term storage of loaded PM filters. As
      part of the TRAPCA study we collected particles with a 50% aerodynamic cut-off
      diameter of 2.5 microm (PM(2.5)) at 40 outdoor sites and particles less than 10
      microm in size (PM(10)) at a subset of these sites (N=12) in Munich. The PM
      filters were cut in halves and endotoxin was measured in the extract of one
      filter half 2-3 years after PM collection. Here we present the results of
      repeated endotoxin measurements, where the association between previously
      measured endotoxin concentrations, measurements from stored eluates, and
      measurements in extracts of the second filter halves were determined. No
      statistically significant changes were seen between our old measurements and
      those from the stored eluates. Additionally, no change was observed between
      previously measured endotoxin concentrations and those from the stored set of
      filter halves. We found an average increase of 5% between our old measurements
      and those from the stored eluates and of 19% between the old measurements and
      those from the stored set of filter halves. The correlations between the
      previously measured endotoxin concentrations and the repeated measurements from
      the stored eluates were high (r=0.789) for EU/m(3) PM(2.5). Since endotoxin was
      evaluated from the same set of filter halves, it is obvious that storage over
      three years did not substantially effect the correlation of the endotoxin
      content. Regarding the outliers from previous measurements unsymmetric endotoxin
      spots on one out of 48 filter halves could be determined. Apart from this we
      conclude that the endotoxin is homogenously distributed on the filter halves and
      that endotoxin levels, which were repeatedly measured from filters stored over
      three years, could be determined validly.

PMID- 17005242
TI  - Hyperhomocysteinemia is a risk factor of recurrent coronary event in young
      patients irrespective to the MTHFR C677T polymorphism.
AB  - Despite the well-known pro-coagulant effect of hyperhomocysteinemia, data is
      limited regarding the result on recurrent coronary event (RCE) in young people.
      One hundred and forty patients <55 years old with a first acute coronary syndrome
      (ACS) were prospectively followed for a mean (+/-S.D.) follow-up of 49+/-14
      months in order to investigate the relationship between homocysteine levels
      (tHcy) at admission and the incidence of RCE. The tHcy values were divided into
      quartiles to examine their relationship with end points. Furthermore, we
      determined the effect of C677T methylene tetrahydrofolate reductase (MTHFR)
      polymorphism, as well as other risk factors for developing a RCE. The median
      plasma homocysteine concentration was 9.6 mumol/L (interquartile range, 3.7). In
      the screening of MTHFR C677T polymorphism in patients with ACS, the T allele
      frequency was 0.4 and the genotype frequency distributions were in Hardy-Weinberg
      equilibrium. At time of final evaluation, 49 (35%) of the 140 valuable patients
      had developed a RCE. Increasing numbers of RCE were observed for increasing
      quartiles of tHcy according to Kaplan-Meier survival (Log-rank test=0.0092). The
      MTHFR C677T polymorphism was not associated with an increased incidence of RCE.
      In multivariate analysis, the variables independently associated with a higher
      risk of RCE were age older than 45 years [HR=2.7; (95% CI, 1.3-6.1); p=0.030],
      body mass index more than 25 [HR=2.6; (95% CI, 1.1-5.9); p=0.034] and tHcy levels
      into quartile 4 (tHcy>12.37 mumol/L) [HR=2.5; (95% CI, 1.1-4.7); p=0.04].
      Elevated plasma homocysteine level at admission is an independent risk factor for
      RCE after the first episode of ACS in young patients irrespective of the status
      of MTHFR C677T.

PMID- 17005243
TI  - Intraplacental choriocarcinoma in a term placenta with both maternal and
      infantile metastases: a case report and review of the literature.
AB  - BACKGROUND: Intraplacental choriocarcinoma is rare, and usually results in
      maternal metastasis at the time of diagnosis. Intraplacental choriocarcinoma
      involves both mother and infant is extremely rare. There was only one case report
      of intraplacental choriocarcinoma with confirmed metastases involving both the
      mother and the infant. CASE: We describe a second case of intraplacental
      choriocarcinoma in a term placenta with both maternal and infantile metastases.
      Grossly, the primary lesion of the placenta resembled an old infarct.
      Microscopically, clusters of malignant trophoblasts arose from residual normal
      chorionic villi and infiltrated into the intervillous spaces. Both the mother and
      the infant received chemotherapy and were alive without disease after one year's
      follow-up. CONCLUSION: The optimal treatment for intraplacental choriocarcinoma
      is controversial. However, aggressive chemotherapy is suggested for patients with
      metastatic disease.

PMID- 17005244
TI  - Ovarian cancer: patterns of surgical care across the United States.
AB  - OBJECTIVE: To describe the primary surgical procedures and procedures for
      intraoperative and postoperative complications, and factors associated with these
      procedures, in women with ovarian cancer. METHODS: Using hospital discharge data
      from nine states, obtained from the Heath Care Cost and Utilization Project from
      1999 to 2002, we evaluated 10,432 women with a primary diagnosis of ovarian
      cancer who underwent at least an oophorectomy for additional procedural ICD-9
      codes during their initial hospitalization. RESULTS: Surgical procedures
      performed in addition to oophorectomy included: omentectomy/debulking 81.9%,
      hysterectomy 73.4%, lymph node dissection 41.4%, appendectomy 23.8%, bowel
      procedures 19.8%, laparoscopy 5.6%, diaphragmatic procedures 4.9%, colostomy
      3.5%, and splenectomy 1.2%. Transfusions were given to 15.5% of patients.
      Intraoperative and postoperative procedures for complications were coded in 7.4%
      of patients, including repair of surgical injury 3.5%, procedures for
      cardiopulmonary complications 2.8%, reoperation 1.1%, and infection treatment
      0.3%. In early stage disease 21.4% of women received no additional staging
      procedures and 46.8% did not have nodal sampling. In bivariate analysis of crude
      rates, factors associated with lymph node dissection were patient age, race,
      payer, teaching hospital status, hospital and surgeon volume, and surgeon
      specialty, p<.01. for all observations. Colostomies were performed by general
      surgeons in 23.1% of cases, by gynecologic oncologists in 2.7% of cases, and by
      obstetrician/gynecologists in no cases, p<.001. Complications were associated
      with age, payer, median household income, and stage, p<.001 for all observations.
      Complication rates were similar for low- and high-volume hospitals and surgeons.
      However, in higher volume settings, significantly more patients received
      debulking procedures, lymph node dissections, and additional surgical procedures,
      p<.001 for all observations. CONCLUSIONS: A significant percentage of women with
      ovarian cancer did not receive recommended surgical procedures. Almost 50% of
      women with early stage disease were not adequately staged and in women with
      advanced disease, the percentage who had additional surgical procedures such as
      bowel resections was much lower than in institutions that report high optimal
      cytoreduction rates.

PMID- 17005245
TI  - Does smoking increase risk of ovarian cancer? A systematic review.
AB  - OBJECTIVES: Although early reports suggested that smoking was not associated with
      ovarian cancer risk, recent studies have reported positive associations for
      cancers of the mucinous subtype. We sought to clarify the relationship between
      smoking and ovarian cancer by histological subtype. METHODS: We conducted a
      systematic literature review and meta-analysis of studies investigating the
      association between smoking and risk of the different histological subtypes of
      epithelial ovarian cancer. Eight population-based case-control studies, one
      pooled analysis of case-control studies, and one cohort study met the inclusion
      criteria. Summary relative risks (RR), 95% confidence intervals (CI), and tests
      for heterogeneity were generated from random effects models. RESULTS: Combined,
      these studies included a total of 910 women with mucinous and 5564 with non
      mucinous ovarian cancers. There was a significant doubling of risk of mucinous
      ovarian cancer in current smokers compared to never smokers (summary RR 2.1, 95%
      CI 1.7-2.7), but no increased risk of serous (1.0, 95% CI 0.8-1.2) or
      endometrioid (0.8, 95% CI 0.6-1.1) cancers and a significant risk reduction for
      clear cell cancers (0.6, 95% CI 0.3-0.9). The risk of mucinous cancer increased
      with increasing amount smoked but returned to that of never smokers within 20-30
      years of stopping smoking. CONCLUSIONS: Meta-analysis suggests that current
      smoking doubles a woman's risk of developing mucinous ovarian cancer. Stopping
      smoking returns the risk to normal in the long term. Smoking may thus be one of
      the few modifiable factors offering potential for primary prevention of mucinous
      ovarian cancer.

PMID- 17005246
TI  - Vulvar cancer metastatic to the breast.
AB  - BACKGROUND: Vulvar cancer rarely sends metastases to distant sites. CASE: A 49
      year-old female presented with a vulvar mass. The histologic examination revealed
      an infiltrating lesion with free surgical margins and no evidence of lymph node
      involvement. Four months following surgery, due to a bloody breast discharge and
      a palpable breast lump an excisional biopsy was performed. The histological
      evaluation revealed morphological features suggestive of metastatic squamous cell
      carcinoma. The morphological, immunohistochemical and in situ hybridization
      findings were consistent with a breast metastatic nodule of squamous cell
      carcinoma arising from the primary vulvar cancer. CONCLUSION: We conclude that
      the specimens are from the same origin therefore making the breast lesion a
      metastasis from the vulva.

PMID- 17005247
TI  - Re: "human papillomavirus testing for primary screening in women at low risk of
      developing cervical cancer. The Greek experience.".

PMID- 17005248
TI  - Sexual health in women treated for cervical cancer: characteristics and
      correlates.
AB  - OBJECTIVE: A large proportion of women with a history of cervical cancer
      experience sexual problems as a result of treatment. The present study examined
      whether differences in sexual health between cervical cancer survivors and women
      with no history of cervical cancer could be explained by selected demographic,
      clinical, and psychosocial and physical factors. METHODS: Women treated between 1
      and 5 years previously for stage 0 to II cervical cancer and age- and education
      matched women with no history of cancer undergoing routine cervical cancer
      screening were recruited to participate. All participants had a partner with whom
      they had ever been sexually active. Women completed measures of sexual health,
      vaginal changes, partner relationship quality, perceived physical appearance, and
      sexual self-concept. RESULTS: Cervical cancer survivors reported significantly
      (p<.05) less sexual interest, more sexual dysfunction, and lower sexual
      satisfaction. The most consistent predictors of sexual health after treatment
      among survivors were time since diagnosis, receipt of radiotherapy, partner
      relations, and perceived physical appearance, as well as vaginal changes. These
      variables accounted for about 50% of the variance in sexual health outcomes.
      CONCLUSION: The findings suggest that efforts to improve sexual health in women
      with a history of cervical cancer must move beyond the direct effects of cancer
      treatment on vaginal anatomy and physiology. Sexual rehabilitation interventions
      should consider partner relationships, perceived physical appearance, and women's
      attitudes toward themselves as sexual beings, in addition to vaginal changes.
      Future research should use prospective longitudinal research designs
      incorporating appropriate comparison groups to further explore this issue.

PMID- 17005249
TI  - Campath-1H induced pure red cell aplasia in a patient with chronic lymphatic
      leukaemia.

PMID- 17005250
TI  - Clinical features and outcome of T-lineage acute lymphoblastic leukemia in
      adults: a low initial white blood cell count, as well as a high count predict
      decreased survival rates.
AB  - Although biological and clinical features differ between B-lineage acute
      lymphoblastic leukemia (ALL) and T-lineage ALL (T-ALL), there have been few
      reports that focused on the prognosis for T-ALL in adults, primarily due to its
      rarity. Here, we studied the long-term outcomes and prognostic factors specific
      for adult T-ALL by combining patient data from the three prospective trials
      conducted by the Japan Adult Leukemia Study Group (JALSG). Among 559 patients
      whose immunophenotypes could be evaluated, 87 (15.6%) were identified as T-ALL.
      Of them, 66 patients (75.8%) achieved complete remission, and relapse occurred in
      41 patients. With a median follow-up for surviving patients of 7.5 years, the
      probability of overall survival was 35.0% at 5 years. Risk factor analysis
      revealed that serum albumin levels, initial white blood cell (WBC) counts, and
      age had independent values for predicting survival. For WBC, not only the high
      count group (50 x 10(9)l(-1) or higher), but also the low-count group (less than
      3 x 10(9)l(-1)) showed a significantly lower survival rates than the intermediate
      count group (p=0.0055 and 0.0037, respectively). Although our findings need
      confirmation, these results will be helpful in the identification of
      prognostically distinct subgroups within adult T-ALL.

PMID- 17005251
TI  - Childhood abuse and neglect in body dysmorphic disorder.
AB  - OBJECTIVE: No published studies have examined childhood abuse and neglect in body
      dysmorphic disorder (BDD). This study examined the prevalence and clinical
      correlates of abuse and neglect in individuals with this disorder. METHODS:
      Seventy-five subjects (69.3% female, mean age=35.4+/-12.0) with DSM-IV BDD
      completed the Childhood Trauma Questionnaire and were interviewed with other
      reliable and valid measures. RESULTS: Of these subjects, 78.7% reported a history
      of childhood maltreatment: emotional neglect (68.0%), emotional abuse (56.0%),
      physical abuse (34.7%), physical neglect (33.3%), and sexual abuse (28.0%). Forty
      percent of subjects reported severe maltreatment. Among females (n=52), severity
      of reported abuse and neglect were .32-.57 standard deviation units higher than
      norms for a health maintenance organization (HMO) sample of women. Severity of
      sexual abuse was the only type of maltreatment significantly associated with
      current BDD severity (r=.23, p=.047). However, severity of sexual abuse did not
      predict current BDD severity in a simultaneous multiple regression analysis with
      age and current treatment status. There were other significant associations with
      childhood maltreatment: history of attempted suicide was related to emotional
      (p=.004), physical (p=.014), and sexual abuse (p=.038). Childhood emotional abuse
      was associated with a lifetime substance use disorder (r=.26, p=.02), and
      physical abuse was negatively associated with a lifetime mood disorder (r=-.37,
      p=.001). CONCLUSIONS: A high proportion of individuals with BDD reported
      childhood abuse and neglect. Certain types of abuse and neglect appear modestly
      associated with BDD symptom severity and with gender, suicidality, and certain
      disorders.

PMID- 17005252
TI  - V(D)J recombination in zebrafish: Normal joining products with accumulation of
      unresolved coding ends and deleted signal ends.
AB  - V(D)J recombination proceeds from a site-specific cleavage to an imprecise end
      joining, via generation and resolution of recombination ends. Although rearranged
      antigen receptor genes isolated from zebrafish (Danio rerio) resemble those made
      in mammals, differences may arise during evolution from lower to higher
      vertebrates, in regard to efficiency, fidelity and regulation of this
      recombination. To elucidate the V(D)J recombination reaction in zebrafish, we
      characterized recombination ends transiently produced by zebrafish lymphocytes,
      as well as joining products. Similar to their mammalian counterpart, zebrafish
      lymphocytes make perfect signal joints and normal coding joints, indicating their
      competent end resolution machinery. However, recombination ends recovered from
      the same zebrafish lymphoid tissues exhibit some features that are not readily
      seen in normal mammalian counterpart: deleted signal ends and accumulation of
      opened coding ends. These results indicate that the recombination reaction in
      zebrafish lymphocytes is inefficient and less stringently regulated, which may
      result from unstable post-cleavage complexes, and/or slow transition from
      cleavage to resolution. Our data suggests that the V(D)J recombination machinery
      may have undergone evolution selection to become more efficient in higher jawed
      vertebrates.

PMID- 17005253
TI  - Synthesis of complement proteins in the human chorion is differentially regulated
      by cytokines.
AB  - The aim of the current paper was to determine the chorion's contribution to
      complement synthesis in the placenta and its regulation by cytokines.
      Biosynthetic labeling followed by immunoprecipitation with polyclonal antibodies
      was performed in chorionic tissue and chorion-derived cells. Eight complement
      proteins, factor B, C3, C1r, C1s, C1 inhibitor, factor H, C4 and C2 were detected
      in chorionic tissue and were secreted extracellularly. In chorion-derived cells,
      IL-1beta stimulated factor B synthesis but had no effect on C1r, C1 inhibitor,
      C1s, factor H and C4. TNFalpha had no stimulative effect on any of the complement
      proteins tested. In contrast, both IL-1beta and TNFalpha highly induced IL-6
      secretion in chorion-derived cells, demonstrating the overall responsiveness of
      these cells to these stimuli. Interestingly, IFN-gamma increased the synthesis of
      C1s, C1r, C1 inhibitor, C4 and factor H in chorion-derived cells. The fact that
      the latter two complement proteins have opposing effects on immune activation of
      the complement cascade demonstrates the complex balance required to both maintain
      an ability to ward off infections but simultaneously suppress the immune response
      to enable tolerance of the allograft fetus.

PMID- 17005254
TI  - Protein arginine methyltransferases: evolution and assessment of their
      pharmacological and therapeutic potential.
AB  - Protein arginine N-methylation is a post-translational modification whose
      influence on cell function is becoming widely appreciated. Protein arginine
      methyltransferases (PRMT) catalyze the methylation of terminal nitrogen atoms of
      guanidinium side chains within arginine residues of proteins. Recently, several
      new members of the PRMT family have been cloned and their catalytic function
      determined. In this report, we present a review and phylogenetic analysis of the
      PRMT found so far in genomes. PRMT are found in nearly all groups of eukaryotes.
      Many human PRMT originated early in eukaryote evolution. Homologs of PRMT1 and
      PRMT5 are found in nearly every eukaryote studied. The gene structure of PRMT
      vary: most introns appear to be inserted randomly into the open reading frame.
      The change in catalytic specificity of some PRMT occurred with changes in the
      arginine binding pocket within the active site. Because of the high degree of
      conservation of sequence among the family throughout evolution, creation of
      specific PRMT inhibitors in pathogenic organisms may be difficult, but could be
      very effective if developed. Furthermore, because of the intricate involvement of
      several PRMT in cellular physiology, their inhibition may be fraught with
      unwanted side effects. Nevertheless, development of pharmaceutical agents to
      control PRMT functions could lead to significant new targets.

PMID- 17005255
TI  - Cerebrovascular risk factors and subsequent depression in older general practice
      patients.
AB  - BACKGROUND: This general practice-based case-control study tested the association
      between cerebrovascular risk factors (CVRFs) and the development of later-life
      depression by focusing on the impact of exposure duration to CVRFs and the
      modifying influence of age at depression onset. METHODS: Cases were 286 patients
      aged > or = 50 years with a first diagnosis of depression at age > or = 50 years.
      Nondepressed controls (N=832) were individually matched for age, gender and
      practice. CVRF diagnoses (hypertension, diabetes mellitus, cardiovascular
      conditions) prior to depression were determined. Analyses controlled for
      education, somatic and nondepressive psychiatric disease. RESULTS: No CVRF
      variable examined was significantly associated with subsequent depression in the
      total sample. An unexpected impact of age at onset of depression was observed:
      the odds ratio associated with having any CVRF was smaller for patients with age
      at onset > or = 70 years than for patients with onset between ages 50-59 years
      (p=.002) and 60-69 years (p=.067). Subsequent analyses excluding patients with
      onset at age > or = 70 years revealed that CVRF variables, including long-term
      exposure to CVRFs, significantly increased the odds of subsequent depression with
      onset between ages 50 and 69 years. LIMITATIONS: Reliance on GPs' records of
      morbidity may have resulted in bias towards underestimation in patients with
      depression onset at age > or = 70 years. CONCLUSIONS: Our findings suggest that
      CVRFs play a relevant role in the development of depression with onset between
      ages 50 and 69 years, but no evidence was found that they contribute to the
      occurrence of depression with onset at age > or = 70 years. Replication is
      warranted to exclude the possibility of bias.

PMID- 17005257
TI  - Revised nomenclature for veterinary allergy.

PMID- 17005256
TI  - Mania, glutamate/glutamine and risperidone in pediatric bipolar disorder: a
      proton magnetic resonance spectroscopy study of the anterior cingulate cortex.
AB  - BACKGROUND: The purpose of this study was to investigate the anterior cingulate
      cortex (ACC) glutamate/glutamine (Glx) to creatine ratio (Glx/Cr) in two groups
      of children with Bipolar Disorder (BPD): those exhibiting manic symptoms
      requiring treatment and those being stably treated with the atypical
      antipsychotic risperidone. Atypical antipsychotics have been shown to increase
      serum glutamate levels and ACC Glx/Cr in subjects with schizophrenia. In this
      study, we hypothesized that the children with BPD in need of treatment would have
      lower Glx/Cr compared with the children with BPD being stably treated with
      risperidone. METHODS: Proton MR spectra were acquired, at 1.5 T, from the ACC of
      eighteen subjects with a DSM-IV diagnosis of BPD: ten (11.10+/-3.48 years; five
      female) were manic and not medicated with any antipsychotic and eight (10.88+/
      2.99 years; one female) were medicated with the atypical antipsychotic
      risperidone. RESULTS: Children with BPD exhibiting manic symptoms requiring
      treatment had lower Glx/Cr than children with BPD being stably treated with the
      atypical antipsychotic risperidone. The children treated with risperidone also
      had significantly lower YMRS and CGI-Mania scores than the children not treated
      with risperidone. Both YMRS and CGI-Mania scores correlated negatively with ACC
      Glx/Cr levels. LIMITATIONS: The cross-sectional design, small sample size, the
      use of Glx rather than glutamate or glutamine and the use of Cr ratios rather
      than absolute concentrations are limitations of this study. CONCLUSIONS: Children
      with mania have lower Glx/Cr levels than children with BPD being stably treated
      with the atypical antipsychotic risperidone. Mania may be associated with reduced
      glutamate/glutamine levels in the ACC: other imaging studies have shown mania
      associated with hypometabolism in the ACC. These reductions in
      glutamate/glutamine may be increased following successful treatment with
      glutamatergic agents.

PMID- 17005259
TI  - Hepatitis A in Tunisia: phylogenetic analysis of hepatitis A virus from 2001 to
      2004.
AB  - Tunisia is a highly endemic area for hepatitis A virus (HAV) infection. In the
      present study, the phylogenetic characterization of the VP1 gene (882
      nucleotides) and of the VP1/2A junction (336 nucleotides) of Tunisian strains
      were examined. One hundred strains isolated from patient with anti-HAV IgM from
      2001 to 2004 were amplified by RT-PCR, sequenced at the VP1 and at the VP1/2A
      junction and aligned with the published sequences to establish phylogenetic
      analysis. All Tunisian strains belong to genotype I with a greater presence of
      sub-genotype IA (98%) originate from most of Tunisian regions and 2% of sub
      genotype IB. In addition, sub-genotype IA and IB strains formed 25 different
      clusters. Genetically similar strains were also identified between 2001 and 2004
      isolated from the southern and the central part of Tunisia, suggesting that an
      indigenous strain has been circulating in the Tunisia. The genetic profile of the
      VP1 region showed that Tun159-02 and Tun40-03 clustered respectively in the IB
      and IA sub-genotype, however, analysis of VP1/2A junction revealed in contrast
      that Tun159-02 and Tun40-03 clustered respectively in IA and IB. This is the
      first report to identify sub-genotype IA in Tunisia and provides new data on the
      genetic relatedness of HAV from Tunisia and the distribution of sub-genotype IA
      in this part of the world.

PMID- 17005258
TI  - Can personalized drug therapy be achieved? A closer look at pharmaco
      metabonomics.
AB  - Between 1930 and 1990, several dozen high-penetrance, predominantly monogenic
      disorders were identified and characterized, which led some investigators to
      speculate that individualized drug treatment was just around the corner.
      Informative DNA tests were sought to determine genetic predisposition to toxicity
      and cancer, thereby identifying individuals in which a drug was likely to be
      effective and those at increased risk of drug toxicity. These assays represent
      the leading edge of phenotype-genotype association studies, which are a major
      goal of clinical pharmacology and pharmacogenomics. Because of the complexity of
      the genome, however, the task is more challenging than anticipated originally. In
      the past decade we have come to appreciate how difficult it is to determine
      unequivocally either an exact phenotype or genotype. In the near future it seems
      unlikely that, by themselves, either transcriptomics or proteomics will be
      particularly helpful in achieving individualized drug therapy. However, recent
      advances in metabonomics are exciting and show promise. In the future, and
      perhaps in combination with proteomics, metabonomics might complement genomics in
      achieving personalized drug therapy.

PMID- 17005261
TI  - Ammonium production during hypo-osmotic stress leads to alkalinization of
      acidocalcisomes and cytosolic acidification in Trypanosoma cruzi.
AB  - Osmotic swelling of Trypanosoma cruzi epimastigotes resulted in alkalinization of
      acidocalcisomes, as revealed by changes in acridine orange fluorescence of intact
      cells. Concomitant with these changes, intracellular ammonium levels increased
      while extracellular ammonium levels decreased significantly. Hypo-osmotic stress
      also resulted in cytosolic acidification. The observed changes in intracellular
      pH (pH(i)) were independent of extracellular calcium, and other ions
      concentration. Taken together, these results are consistent with a stimulation of
      ammonium production upon hypo-osmotic stress and its accumulation in
      acidocalcisomes resulting in their alkalinization, which might be responsible for
      polyphosphate hydrolysis and osmotic changes in the organelles.

PMID- 17005260
TI  - Evidence of direct interactions between the CC-chemokines CCL3, CCL4 and CCL5 and
      Leishmania promastigotes.

PMID- 17005262
TI  - Peptidomic analysis of skin secretions from Rana heckscheri and Rana okaloosae
      provides insight into phylogenetic relationships among frogs of the Aquarana
      species group.
AB  - The members of the Aquarana (or Rana catesbeiana species group) form a
      monophyletic group comprising seven species: R. catesbeiana, Rana clamitans, Rana
      grylio, Rana virgatipes, Rana septentrionalis, Rana heckscheri and Rana
      okaloosae. Previous work has led to structural characterization of the
      antimicrobial peptides present in electrically-stimulated skin secretions from
      the first five species listed and this study presents the primary structures of
      orthologs from the river frog R. heckscheri and the Florida bog frog R.
      okaloosae. Peptidomic analysis of R. heckscheri and R. okaloosae skin secretions
      led to the identification of peptides with antimicrobial activity belonging to
      the ranalexin, ranatuerin-2, and temporin families. In addition, a peptide
      (GFLDIIKDTGKDFAVKILNNLKCKLAGGCPR) was isolated from R. okaloosae whose primary
      structure identified it as a member of the palustrin-2 family. Consistent with
      previous data based upon morphological analysis and comparisons of the nucleotide
      sequences of mitochondrial and ribosomal genes, cladistic analysis based upon a
      comparison of the amino acid sequences of antimicrobial peptides indicates a
      sister-group relationship between R. heckscheri and R. grylio and a close, but
      less well defined, phylogenetic relationship between R. okaloosae and R.
      clamitans.

PMID- 17005263
TI  - Signaling pathways involved in atrial natriuretic factor and dopamine regulation
      of renal Na+, K+ -ATPase activity.
AB  - Dopamine (DA) and atrial natriuretic factor (ANF) share a number of physiological
      effects. We hypothesized that ANF and the renal dopaminergic system could
      interact and enhance the natriuretic and diuretic effects of the peptide. We have
      previously reported that the ANF-stimulated DA uptake in renal tubular cells is
      mediated by the natriuretic peptide type-A receptor (NPR-A). Our aim was to
      investigate the signaling pathways that mediate ANF effects on renal 3H-DA
      uptake. Methylene blue (10 microM), an unspecific inhibitor of guanylate cyclase
      (GC), blunted ANF elicited increase of DA uptake. ODQ (10 microM) a specific
      inhibitor of soluble GC, did not modify DA uptake and did not reverse ANF-induced
      increase of DA uptake; then the participation of nitric oxide-dependent pathways
      must be discarded. The second messenger was the cGMP since the analogous 125
      microM 8-Br-cGMP mimicked ANF effects. The specific inhibitor of the protein
      kinase G (PKG), KT 5823 (1 microM) blocked ANF effects indicating that PKG is
      involved. We examined if ANF effects on DA uptake were able to modify Na+, K+ 
      adenosine triphosphatase (Na+, K+ -ATPase) activity. The experiments were
      designed by means of inhibition of renal DA synthesis by carbidopa and neuronal
      DA uptake blocked by nomifensine. In these conditions renal Na+, K+ -ATPase
      activity was increased, in agreement with the decrease of DA availability. When
      in similar conditions, exogenous DA was added to the incubation medium, the
      activity of the enzyme tended to decrease, following to the restored availability
      of DA. The addition of ANF alone had similar effects to the addition of DA on the
      sodium pump, but when both were added together, the activity of Na(+), K(+)
      ATPase was decreased. Moreover, the extraneuronal uptake blocker, hydrocortisone,
      inhibited the latter effect. In conclusion, ANF stimulates extraneuronal DA
      uptake in external cortex tissues by activation of NPR-A receptors coupled to GC
      and it signals through cGMP as second messenger and PKG. Dopamine and ANF may
      achieve their effects through a common pathway that involves reversible
      deactivation of renal tubular Na+, K+ -ATPase activity. This mechanism
      demonstrates a DA-ANF relationship involved in the modulation of both decreased
      sodium reabsorption and increased natriuresis.

PMID- 17005264
TI  - Cofactor CLIM2 promotes the repressive action of LIM homeodomain transcription
      factor Lhx2 in the expression of porcine pituitary glycoprotein hormone alpha
      subunit gene.
AB  - We have cloned a porcine orthologue of cofactor CLIM2 (Ldb1/NLI) from the porcine
      pituitary cDNA library by protein-protein interaction with the Yeast Two-Hybrid
      System using porcine Lhx2 as a bait protein. Porcine CLIM2 shows a high identity
      (99%) in the dimerization domain, nuclear localization signal and LIM binding
      domain with those of man and mouse. The expression of CLIM2 gene in the anterior
      pituitary lobe was detected during the porcine fetal and postnatal period by RT
      PCR analysis, suggesting that this protein is constitutively expressing and plays
      a basic role in the anterior pituitary. Transfection assay to the pituitary tumor
      derived LbetaT2 cells, and the Chinese hamster ovary cells demonstrated that
      CLIM2 acts as a corepressor of the porcine Lhx2 function. Interestingly, CLIM2
      alone apparently repressed the high level of alphaGSU gene expression in LbetaT2
      cells. These data suggest that CLIM2 is a basic factor in the pituitary
      development and function, and plays the role of repressor to modify the function
      of Lhx2 on the alphaGSU gene expression.

PMID- 17005265
TI  - New perspectives on the role of SERCA2's Ca2+ affinity in cardiac function.
AB  - Cardiomyocyte relaxation and contraction are tightly controlled by the activity
      of the cardiac sarco(endo)plasmic reticulum (SR) Ca2+ transport ATPase (SERCA2a).
      The SR Ca2+ -uptake activity not only determines the speed of Ca(2+) removal
      during relaxation, but also the SR Ca2+ content and therefore the amount of Ca2+
      released for cardiomyocyte contraction. The Ca2+ affinity is the major
      determinant of the pump's activity in the physiological Ca2+ concentration range.
      In the heart, the affinity of the pump for Ca2+ needs to be controlled between
      narrow borders, since an imbalanced affinity may evoke hypertrophic
      cardiomyopathy. Several small proteins (phospholamban, sarcolipin) adjust the
      Ca2+ affinity of the pump to the physiological needs of the cardiomyocyte. It is
      generally accepted that a chronically reduced Ca2+ affinity of the pump
      contributes to depressed SR Ca2+ handling in heart failure. Moreover, a
      persistently lower Ca2+ affinity is sufficient to impair cardiomyocyte SR Ca2+
      handling and contractility inducing dilated cardiomyopathy in mice and humans.
      Conversely, the expression of SERCA2a, a pump with a lower Ca2+ affinity than the
      housekeeping isoform SERCA2b, is crucial to maintain normal cardiac function and
      growth. Novel findings demonstrated that a chronically increased Ca2+ affinity
      also may trigger cardiac hypertrophy in mice and humans. In addition, recent
      studies suggest that some models of heart failure are marked by a higher affinity
      of the pump for Ca2+, and hence by improved cardiomyocyte relaxation and
      contraction. Depressed cardiomyocyte SR Ca2+ uptake activity may therefore not be
      a universal hallmark of heart failure.

PMID- 17005266
TI  - Arabidopsis thaliana--a model organism to study plant peroxisomes.
AB  - In higher plants, peroxisomes have been believed to play a pivotal role in three
      metabolic pathways, which are lipid breakdown, photorespiration and H2O2
      detoxificaton. Recently, significant progress in the study of plant peroxisomes
      was established by forward-/reverse-genetics and post-genomic approaches using
      Arabidopsis thaliana, the first higher plant to have its entire genome sequenced.
      These studies illustrated that plant peroxisomes have more diverse functions than
      we previously thought. Research using Arabidopsis thaliana is improving our
      understanding of the function of plant peroxisomes.

PMID- 17005268
TI  - Sharing the wealth: peroxisome inheritance in budding yeast.
AB  - Eukaryotic cells have evolved molecular mechanisms to ensure the faithful
      partitioning of cellular components during cell division. The budding yeast
      Saccharomyces cerevisiae has to actively deliver about half of its organelles to
      the growing bud, while retaining the remaining organelles in the mother cell.
      Until lately, little was known about the inheritance of peroxisomes. Recent
      studies have identified the peroxisomal proteins Inp1p and Inp2p as two key
      regulators of peroxisome inheritance that perform antagonistic functions. Inp1p
      is required for the retention of peroxisomes in mother cells, whereas Inp2p
      promotes the bud-directed movement of these organelles. Inp1p anchors peroxisomes
      to the cell cortex by interacting with specific structures lining the cell
      periphery. On the other hand, Inp2p functions as the peroxisome-specific receptor
      for the class V myosin, Myo2p, thereby linking peroxisomes to the translocation
      machinery that propels peroxisome movement. Tight coordination between Inp1p and
      Inp2p ensures a fair and harmonious spatial segregation of peroxisomes upon cell
      division.

PMID- 17005267
TI  - Bafilomycin A1-sensitive pathway is required for the maturation of cystic
      fibrosis transmembrane conductance regulator.
AB  - Cystic fibrosis (CF) is the most common lethal genetic disease in Caucasians
      caused by the trafficking defects of CF transmembrane conductance regulator
      (CFTR), which is a cAMP-dependent Cl- channel at the plasma membrane. The
      trafficking pathway of CFTR is thought to be non-conventional because CFTR
      maturation is inhibited by the dysfunction of syntaxin 13, which is involved in
      protein recycling via endosomal pathway. In this study, to clarify whether the
      endosomal trafficking is required for CFTR maturation, we utilized a specific
      vacuolar H+-ATPase inhibitor, bafilomycin A1 (BafA1), which inhibits the protein
      trafficking from early endosome. Our data showed that low concentration of BafA1
      (50 nM) decreased the expression of mature CFTR but induced the accumulation of
      immature CFTR in the juxta-nuclear region containing an early endosome marker.
      Pulse-chase analysis showed that BafA1 inhibited the maturation of CFTR, but it
      slightly stabilized immature CFTR. These results indicate that BafA1-sensitive
      pathway is required for CFTR maturation and emphasize that endosomal trafficking
      pathway might be involved in the maturation of CFTR.

PMID- 17005269
TI  - Transcriptome analysis of fetal metatarsal long bones by microarray, as a model
      for endochondral bone formation.
AB  - Endochondral bone formation is orchestrated by mesenchymal cell condensation to
      form cartilage anlagen, which act as a template for bone formation and eventual
      mineralization. The current study performed gene expression analysis to examine
      pre- and post-mineralization stages (E15 and E19) of endochondral bone formation,
      using fetal metatarsal long bones as a model. An extensive number of genes were
      differentially expressed, with 543 transcripts found to have at least 2-fold up
      regulation and 742 with a greater than 2-fold down-regulation. A bioinformatics
      approach was adopted based on gene ontology groups, and this identified genes
      associated with the regulation of signaling and skeletal development, cartilage
      replacement by bone, and matrix degradation and turnover. Transcripts linked to
      skeletal patterning, including Hoxd genes 10-12, Gli2 and Noggin were
      considerably down-regulated at E19. Whereas genes associated with bone matrix
      formation and turnover, ACP5, MMP-13, bone sialoprotein, osteopontin, dentin
      matrix protein-1 and MMP-9 all were distinctly up-regulated at this later time
      point. This approach to studying the formation of the primary ossification center
      provides a unique picture of the developmental dynamics involved in the molecular
      and biochemical processes during this intricately regulated process.

PMID- 17005270
TI  - PTS1-independent sorting of peroxisomal matrix proteins by Pex5p.
AB  - Most peroxisomal matrix proteins contain a peroxisomal targeting signal 1 (PTS1)
      for sorting to the correct organelle. This signal is located at the extreme C
      terminus and generally consists of only three amino acids. The PTS1 is recognized
      by the receptor protein Pex5p. Several examples have been reported of peroxisomal
      matrix proteins that are sorted to peroxisomes via Pex5p, but lack a typical PTS1
      tripeptide. In this contribution we present an overview of these so-called non
      PTS1 proteins and discuss the current knowledge of the molecular mechanisms
      involved in their sorting.

PMID- 17005271
TI  - Pexophagy: autophagic degradation of peroxisomes.
AB  - The abundance of peroxisomes within a cell can rapidly decrease by selective
      autophagic degradation (also designated pexophagy). Studies in yeast species have
      shown that at least two modes of peroxisome degradation are employed, namely
      macropexophagy and micropexophagy. During macropexophagy, peroxisomes are
      individually sequestered by membranes, thus forming a pexophagosome. This
      structure fuses with the vacuolar membrane, resulting in exposure of the
      incorporated peroxisome to vacuolar hydrolases. During micropexophagy, a cluster
      of peroxisomes is enclosed by vacuolar membrane protrusions and/or segmented
      vacuoles as well as a newly formed membrane structure, the micropexophagy
      specific membrane apparatus (MIPA), which mediates the enclosement of the
      vacuolar membrane. Subsequently, the engulfed peroxisome cluster is degraded.
      This review discusses the current state of knowledge of pexophagy with emphasis
      on studies on methylotrophic yeast species.

PMID- 17005272
TI  - Effects of simvastatin on plasma antioxidant status and vitamins in
      hypercholesterolemic patients.
AB  - BACKGROUND: Statins are known to possess antioxidant properties in addition to
      their cholesterol-lowering effects. However, recent studies have suggested that
      statins reduce the levels of antioxidant vitamins such as vitamin E and coenzyme
      Q(10), possibly resulting in impaired left ventricular function. We investigated
      the effects of simvastatin on the blood lipids, LDL oxidation and plasma
      antioxidant status, and whether these effects were associated with changes in
      plasma antioxidant vitamin levels. METHODS: Simvastatin (20-40 mg/day) was
      administered for 8 weeks in seventy-six hypercholesterolemic patients. We
      measured plasma lipids, oxidized LDL, total radical trapping antioxidant
      potential (TRAP) and plasma antioxidant vitamin levels at baseline and after 8
      weeks of simvastatin administration. RESULTS: Simvastatin significantly lowered
      serum levels of total cholesterol and LDL-cholesterol by 30.1% and 41.9%,
      respectively. A significant reduction in oxidized LDL levels (p<0.0001) and
      improvement in plasma antioxidant status as measured by TRAP (p<0.05) after the 8
      week simvastatin treatment were observed. Regarding the effects of simvastatin on
      plasma antioxidant vitamin levels, there were significant increases in the levels
      of lipid-corrected retinol (p<0.001), alpha-tocopherol (p<0.001) and gamma
      tocopherol (p<0.005) after the 8-week simvastatin treatment. Lipid-corrected
      levels of coenzyme Q10 and carotenoids remained unchanged after simvastatin
      treatment. CONCLUSIONS: Our results show that simvastatin reduced blood lipids
      and circulating oxidized LDL, and improved plasma antioxidant status without
      altering the antioxidant vitamin system. These data indicate that simvastatin not
      only decreases blood lipids and circulating oxidized LDL but also increases lipid
      corrected levels of antioxidant vitamins and may improve plasma antioxidant
      status synergizing with the biological effects of antioxidants.

PMID- 17005273
TI  - Marijuana as a trigger of cardiovascular events: speculation or scientific
      certainty?
AB  - Marijuana is the most widely used illicit substance in the United States.
      Cardiovascular complications in association with marijuana use have been reported
      during the past three decades. In view of the elevated public interest in this
      drug's role in pharmacotherapy in the recent years and the aging population of
      long-term marijuana users from the late 1960s, encounters with marijuana-related
      cardiovascular adversities may be silently on the rise. The purpose of this
      article is to increase awareness of the potential of marijuana to lead to
      cardiovascular disease. Here, we will discuss the physiologic effects of
      marijuana and include a comprehensive review of the studies and case reports that
      provide supportive evidence for marijuana as a trigger of adverse cardiovascular
      events, including tachyarrhythmias, acute coronary syndrome, vascular
      complications, and even congenital heart defects.

PMID- 17005275
TI  - Trichomonas vaginalis detection using real-time TaqMan PCR.
AB  - 1978 women and 93 men, all suspected of having a Trichomonas vaginalis infection,
      were tested for the presence of T. vaginalis by real-time PCR using the T.
      vaginalis-specific 2-kb repeated sequence, and by direct microscopy and culture.
      40 samples were positive by T. vaginalis real-time PCR and 27 were positive by
      wet mount microscopy, either direct or after culture. All samples positive by
      direct microscopy of culture were also positive by real-time PCR. Of the 13
      samples which were real-time PCR positive but negative by direct microscopy and
      culture 11 were confirmed by another T. vaginalis real-time PCR based on the beta
      tubulin gene. Only 2 samples (0.1%) showed inhibition in the PCR. The prevalence
      of T. vaginalis infection in the female patients was 1.8%. The sensitivity,
      specificity, positive and negative predictive values of the real-time PCR were
      100%, 99.9%, 95% and 100%, respectively. The same test characteristics for the
      combined conventional T. vaginalis detection methods (microscopy+culture) were
      71%, 100%, 100% and 99%, respectively. Therefore, real-time PCR is the method of
      choice for the diagnosis of T. vaginalis infection.

PMID- 17005276
TI  - Optimized candidal biofilm microtiter assay.
AB  - Microtiter based candidal biofilm formation is commonly being used. Here we
      describe the analysis of factors influencing the development of candidal biofilms
      such as the coating with serum, growth medium and pH. The data reported here show
      that optimal candidal biofilm formation is obtained when grown in unbuffered YNB
      at pH 7, in wells that have been coated with Fetal Calf Serum or Fetal Bovine
      Serum.

PMID- 17005277
TI  - New light for science: synchrotron radiation in structural medicine.
AB  - Macromolecular crystallography (MX) is a powerful method for obtaining detailed
      three-dimensional structural information about macromolecules. MX using
      synchrotron X-rays has contributed, significantly, to both fundamental and
      applied research, including the structure-based design of drugs to combat
      important diseases. New third-generation synchrotrons offer substantial
      improvements in terms of quality and brightness of the X-ray beams they produce.
      Important classes of macromolecules, such as membrane proteins (including many
      receptors) and macromolecular complexes, are difficult to obtain in quantity and
      to crystallise, which has hampered analysis by MX. Intensely bright X-rays from
      the latest synchrotrons will enable the use of extremely small crystals, and
      should usher in a period of rapid progress in resolving these previously
      refractory structures.

PMID- 17005278
TI  - Impact of target point deviations on control and complication probabilities in
      stereotactic radiosurgery of AVMs and metastases.
AB  - OBJECTIVE: Determination of the impact of inaccuracies in the determination and
      setup of the target point in stereotactic radiosurgery (SRS) on the expectable
      complication and control probabilities. METHODS: Two randomized samples of
      patients with arteriovenous malformation (AVM) (n=20) and with brain metastases
      (n=20) treated with SRS were formed, and the probability for complete
      obliteration (COP) or complete remission (CRP), the size of the 10 Gy-volume in
      the brain tissue (VOI10), and the probability for radiation necrosis (NTCP) were
      calculated. The dose-effect relations for COP and CRP were fitted to clinical
      data. Target point deviations were simulated through random vectors and the
      resulting probabilities and volumes were calculated and compared with the values
      of the treatment plan. RESULTS: The decrease of the relative value of the control
      probabilities at 1mm target point deviation was up to 4% for AVMs and up to 10%
      for metastases. At 2 mm the median decrease was 5% for AVMs and 9% for
      metastases. The value for the target point deviation, at which COP and CRP
      decreased about 0.05 in 90% of the cases, was 1.3 mm. The increase of NTCP was
      maximally 0.0025 per mm target point deviation for AVMs and 0.0035/mm for
      metastases. The maximal increase of VOI10 was 0.7 cm(3)/mm target point deviation
      in both patient groups. CONCLUSIONS: The upper limit for tolerable target point
      deviations is at 1.3mm. If this value cannot be achieved during the system test,
      a supplementary safety margin should be applied for the definition of the target
      volume. A better accuracy level is desirable, in order to ensure optimal chances
      for the success of the treatment. The target point precision is less important
      for the minimization of the probability of radiation necroses.

PMID- 17005279
TI  - Dose optimisation in single plane interstitial brachytherapy.
AB  - BACKGROUND AND PURPOSE: Brachytherapy dose distributions can be optimised by
      modulation of source dwell times. In this study dose optimisation in single
      planar interstitial implants was evaluated in order to quantify the potential
      benefit in patients. MATERIAL AND METHODS: In 14 patients, treated for recurrent
      rectal and cervical cancer, flexible catheters were sutured intra-operatively to
      the tumour bed in areas with compromised surgical margin. Both non-optimised,
      geometrically and graphically optimised CT -based dose plans were made. The
      overdose index (OI), homogeneity index (HI), conformal index (COIN), minimum
      target dose, and high dose volumes were evaluated. The dependence of OI, HI, and
      COIN on target volume and implant regularity was evaluated. In addition, 12
      theoretical implant configurations were analyzed. RESULTS: Geometrical and
      graphical optimisation improved the dose plans significantly with graphical
      optimisation being superior. Graphically optimised dose plans showed a
      significant decrease of 18%+/-9% in high dose volume (p<0.001). HI, COIN, and OI
      were significantly improved from 0.50+/-0.05 to 0.60+/-0.05, from 0.65+/-0.04 to
      0.71+/-0.04, and from 0.19+/-0.03 to 0.15+/-0.03, respectively (p<0.001 for all).
      Moreover, minimum target dose increased significantly from 71%+/-5% to 80%+/-5%
      (p<0.001). The improvement in OI and HI obtained by optimisation depended on the
      regularity of the implant, such that the benefit of optimisation was larger for
      irregular implants. OI and HI correlated strongly with target volume limiting the
      usability of these parameters for comparison of dose plans between patients.
      CONCLUSIONS: Dwell time optimisation significantly improved the dose distribution
      regarding homogeneity, conformity, minimum target dose, and size of high dose
      volumes. Graphical optimisation is fast, reproducible and superior to geometric
      optimisation.

PMID- 17005280
TI  - Dosimetric comparison of helical tomotherapy treatment and step-and-shoot
      intensity-modulated radiotherapy of retroperitoneal sarcoma.
AB  - PURPOSE: To compare step-and-shoot intensity-modulated radiation therapy (SAS
      IMRT) and helical tomotherapy (Tomo) dosimetry plans for patients who have
      received adjuvant radiation therapy for retroperitoneal sarcomas (RSTS). METHODS
      AND MATERIALS: A retrospective review was performed for seven patients who
      received either SAS-IMRT or Tomo as adjuvant radiation therapy for RSTS. In each
      case, a treatment plan of the other modality was generated so that SAS-IMRT and
      Tomo could be compared. RESULTS: The average percentage of clinical target volume
      (CTV) that received less than the prescription dose was 1.4% for Tomo compared to
      3.8% for SAS-IMRT. Both SAS-IMRT and Tomo plans provided comparable and
      significant reductions in volume of small bowel receiving greater than 45 Gy
      compared to simple opposing standard radiation fields. For the ipsilateral
      kidney, Tomo significantly reduced the volume of kidney that received at least 15
      Gy (average 22% for Tomo vs. 56% for SAS-IMRT). CONCLUSION: Both SAS-IMRT and
      Tomo can encompass the large CTV often required for patients with RSTS, although
      Tomo provides superior dose uniformity. Both SAS-IMRT and Tomo can minimize the
      volume of small bowel receiving greater than 45 Gy. Tomo was superior to SAS-IMRT
      in minimizing the volume of ipsilateral kidney irradiated to greater than 15 Gy
      when the CTV is adjacent to a kidney. Dose escalation and target margin expansion
      may thus become realistic possibilities.

PMID- 17005281
TI  - Mapping of the RXRalpha binding elements involved in retinoic acid induced
      transcriptional activation of the human SOX3 gene.
AB  - Sox3/SOX3 gene is implicated in the control of nervous system development and is
      considered to be one of the earliest neural markers. Expression of human SOX3
      gene is modulated during the RA-induced neuronal differentiation cascade of
      NT2/D1 cells. Our present results demonstrate that the sequences responsible for
      RA-induced activation of SOX3 gene are localized within the 0.4 kb of its 5'
      flanking region and implicate RXRalpha involvement in this regulation. The active
      RA/RXRalpha responsive region is pinned down to two regulatory elements. Only in
      the presence of both elements full RA/RXRalpha inducibility is achieved,
      suggesting they act synergistically. These elements comprise two unique G-rich
      boxes, separated by 49 bp, that could be considered as a novel, atypical RA
      response element. Here, for the first time, we have demonstrated direct
      interaction of RXRalpha and SOX3 control elements. Furthermore, the functional in
      vivo analysis revealed that liganded RXRalpha is a potent activator of endogenous
      SOX3 protein expression. Since it is proven that Sox3 is critical determinant of
      neurogenesis our data may help in providing new insight into complex regulatory
      networks involved in retinoic acid induced neural differentiation of NT2/D1
      cells.

PMID- 17005282
TI  - Intracellular binding of fukutin and alpha-dystroglycan: relation to
      glycosylation of alpha-dystroglycan.
AB  - The functions of fukutin, a gene product responsible for Fukuyama type congenital
      muscular dystrophy, still remain unclear, although a relation to the
      glycosylation of alpha-dystroglycan is presumed. To investigate the functions of
      fukutin, immunohistochemistry, examination using cultured astrocytes, enzyme
      linked immunosorbent assay (ELISA)-based binding assay and immunoprecipitation
      were performed using control muscle and central nervous system tissues.
      Immunohistochemistry showed that alpha-dystroglycan and fukutin were co
      expressed, especially in the glial cytoplasm and glia limitans of the central
      nervous system. An anti-fukutin antibody added to the culture medium did not
      bring about any changes in the astrocytes cultured on laminin-coated dishes.
      Together with the immunohistochemical results, the intracellular function of
      fukutin is considered. ELISA-based binding assay and immunoprecipitation may
      suggest the direct binding of fukutin and alpha-dystroglycan, at least in part.
      Fukutin seems to bind to both the hypoglycosylated and fully glycosylated form of
      alpha-dystroglycan, and seems bind to the core area rather than the sugar chain
      of alpha-dystroglycan. Fukutin may directly interact with alpha-dystroglycan
      during glycosylation, but further examinations are needed to confirm these
      details.

PMID- 17005283
TI  - Direct detection of antibiotic resistance genes in specimens of chicken and pork
      meat.
AB  - Antibiotic resistance (AR) in bacteria, a major threat to human health, has
      emerged in the last few decades as a consequence of the selective pressure
      exerted by the widespread use of antibiotics in medicine, agriculture and
      veterinary practice and as growth promoters in animal husbandry. The frequency of
      11 genes [tet(M), tet(O), tet(K), erm(A), erm(B), erm(C), vanA, vanB, aac (6')-Ie
      aph (2'')-Ia, mecA, blaZ] encoding resistance to some antibiotics widely used in
      clinical practice was analysed in raw pork and chicken meat and in fermented
      sausages as well as in faecal samples from the relevant farm animals using a
      molecular approach based on PCR amplification of bacterial DNA directly extracted
      from specimens. Some of the 11 AR genes were highly prevalent, the largest number
      being detected in chicken meat and pig faeces. The genes found most frequently in
      meat were tet(K) and erm(B); vanB and mecA were the least represented. All 11
      determinants were detected in faecal samples except mecA, which was found only in
      chicken faeces. erm(B) and erm(C) were detected in all faecal samples. The
      frequency of AR genes was not appreciably different in meat compared to faecal
      specimens of the relevant animal except for vanB, which was more prevalent in
      faeces. Our findings suggest that AR genes are highly prevalent in food
      associated bacteria and that AR contamination is likely related to breeding
      rather than processing techniques. Finally, the cultivation-independent molecular
      method used in this work to determine the prevalence of AR genes in foods proved
      to be a rapid and reliable alternative to traditional tools.

PMID- 17005284
TI  - Variable intensity of purifying selection on cytotoxic T-lymphocyte epitopes in
      hepatitis C virus.
AB  - In an analysis of the patterns of nucleotide diversity in 26 datasets providing
      population-level data on different genomic regions of different hepatitis C virus
      (HCV) subtypes, known cytotoxic T-lymphocyte (CTL) epitope regions in most cases
      showed evidence of the occurrence of purifying selection. Two main factors were
      found to be associated with the strength of purifying selection: (1) purifying
      selection was stronger in CTL epitopes in non-envelope proteins than in envelope
      proteins and (2) purifying selection was stronger when the epitope was "matched",
      i.e., when the described or "canonical" epitope sequence was present unaltered in
      at least one sequence in the dataset. Of all polymorphic sites, non-synonymous
      sites in matched CTL epitopes in non-envelope proteins had the lowest gene
      diversities, implying that these variants are subject to ongoing purifying
      selection. This in turn suggests that the population frequency of such variants
      may of be the result of a balance between opposing forces: on the one hand,
      positive selection favoring escape mutants in hosts that express the presenting
      MHC molecule and, on the other hand, purifying selection acting, in the absence
      of the presenting MHC molecule, to reduce the frequency of slightly deleterious
      variants.

PMID- 17005285
TI  - Sequence variability of retroviral particles derived from human melanoma cells
      melanoma-associated retrovirus.
AB  - We have shown that melanoma cells produce viral particles that contain sequences
      which are homologous to human endogenous retroviruses. In this study particles
      derived from different melanoma cell lines and from melanoma cells of a lymph
      node metastasis were characterized. We determined the density and the reverse
      transcriptase (RT) activity of viral particles. Furthermore, we analyzed the
      sequence variability of multiple clones of each particle preparation. The
      particles were found to package sequences, which vary for each of the analyzed
      cell lines. Moreover, even particles derived from the same cell line contain
      heterologous sequences.

PMID- 17005286
TI  - Erbium:YAG laser-mediated oligonucleotide and DNA delivery via the skin: an
      animal study.
AB  - Topical delivery of antisense oligonucleotides (ASOs) and DNA is attractive for
      treatment of skin disorders. However, this delivery method is limited by the low
      permeability of the stratum corneum (SC). The objective of this study was to
      enhance and optimize the skin absorption of gene-based drugs by an erbium:yttrium
      aluminum-garnet (Er:YAG) laser. The animal model utilized nude mice. In the in
      vitro permeation study, the Er:YAG laser treatment produced a 3-30-fold increase
      in ASO permeation which was dependent on the laser fluence and ASO molecular mass
      used. The fluorescence microscopic images showed a more-significant localization
      of a 15-mer ASO in the epidermis and hair follicles after laser application as
      compared with the control. The expressions of reporter genes coding for beta
      galactosidase and green fluorescent protein (GFP) in skin were assessed by X-gal
      staining and confocal laser scanning microscopy. The SC ablation effect and
      photomechanical waves produced by the Er:YAG laser resulted in DNA expression
      being extensively distributed from the epidermis to the subcutis. The GFP
      expression in 1.4 J/cm2-treated skin was 160-fold higher than that in intact
      skin. This non-invasive, well-controlled technique of using an Er:YAG laser for
      gene therapy provides an efficient strategy to deliver ASOs and DNA via the skin.

PMID- 17005287
TI  - Myocardial regeneration strategies using human embryonic stem cell-derived
      cardiomyocytes.
AB  - Regenerative medicine is a new biomedicine discipline that takes advantage of the
      recent advancements in the fields of stem cell biology, molecular biology, and
      tissue engineering to derive tissue substitutes, in an attempt to replace or
      modify the function of diseased organs. The heart represents an attractive
      candidate for these emerging technologies since adult cardiac tissue has limited
      regenerative capacity. Consequentially, myocardial cell replacement therapy has
      emerged as a novel therapeutic paradigm for restoration of the myocardial
      electromechanical function. This innovative strategy has been significantly
      hampered, however, by the paucity of cell sources for human cardiomyocytes. The
      recent establishment of the human embryonic stem cell (hESC) lines may provide a
      possible solution for this cell-sourcing problem. These unique pluripotent cell
      lines can be propagated in the undifferentiated state in culture and coaxed to
      differentiate into cell derivatives of all three germ layers, including
      cardiomyocytes. This review will describe the hESC system, their differentiation
      into cardiomyocytes, and the structural and functional characterization of these
      cardiac lineage derivatives. The potential applications of this unique
      differentiating system in several research areas will be discussed with special
      emphasis on the steps required to fully harness their unique potential in the
      emerging field of cardiovascular regenerative medicine.

PMID- 17005288
TI  - The CD4(+) regulatory T-cells is decreased in adults with latent autoimmune
      diabetes.
AB  - The latent autoimmune diabetes in adults (LADA) is a subgroup of type 1 diabetes,
      which procession of autoimmune destruction of beta-cells was slower than classic
      type 1 diabetes. To investigate the pathogenesis of LADA, we examined the
      lymphocyte subsets including the CD4(+)CD25(+) T-cells in 60 LADA patients and 30
      patients of type 2 diabetes and 30 healthy individuals by FACS. And we compared
      the expression of FOXP3 mRNA in CD4(+) T-cell between 10 patients of LADA and 10
      matched healthy individuals by real time PCR. The percent of CD4(+)CD25(+) T
      cells were higher (11.89+/-4.96% versus 8.16+/-3.65%, P<0.01), and the percent
      CD8(+) T-cells elevated (24.58+/-6.80% versus 19.39+/-7.12, P<0.01) in LADA
      patients than healthy individuals. While the expression of FOXP3 mRNA in CD4(+) T
      cell was markedly decreased in LADA patients (0.52-fold, n=10, P=0.004) compared
      with normal subjects. In addition, the percent of CD8(+) T-cells related with GAD
      Ab titers in LADA patients (r=0.292, P=0.03). Our results showed that there were
      cellular immune disorder and decreased CD4(+) regulatory T-cells in LADA
      patients. The adoptive transfer regulatory T-cells seem to be a potential
      therapeutics for LADA.

PMID- 17005289
TI  - Prevalence of diabetes in Pakistan.
AB  - The prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) and
      the contributing risk factors were estimated by performing a cross-sectional
      survey conducted earlier in the rural and urban areas of all the four provinces
      of Pakistan. The statistical analysis was performed from the obtained results by
      using SPSS version 12.0. The total number of subjects examined were 5433 which
      included 1893 males (1208 in rural and 685 in urban areas) and 3540 females (2243
      in rural and 1297 in urban areas). The prevalence of diabetes in the urban versus
      the rural areas was 6.0% in men and 3.5% in women against 6.9% in men and 2.5% in
      women, respectively. Newly diagnosed diabetes was 5.1% in men and 6.8% in women
      in urban areas and 5.0% in men and 4.8% in women in rural areas. IGT in the urban
      versus the rural areas was 6.3% in men and 14.2% in women against 6.9% in men and
      10.9% in women, respectively. Overall glucose intolerance (DM+IGT) was 22.04% in
      urban and 17.15% in rural areas. The major risk factors identified were age,
      positive family history and obesity especially central obesity.

PMID- 17005290
TI  - Multiple voxel 1H MR spectroscopy of phosphorylase-b kinase deficient patients
      (GSD IXa) showing an accumulation of fat in the liver that resolves with aging.
AB  - BACKGROUND/AIMS: Phosphorylase-b deficient patients suffer from glycogen storage
      disease (GSD IXa) leading to liver enlargement which usually resolves during
      puberty and adolescence. This pathology has not yet been documented by (1)H MR
      spectroscopy (MRS) investigation. METHODS: MRS of eight GSD IXa patients was
      performed in this study to assess whether or not liver fat content is elevated in
      GSD IXa and decreases with aging. An improvement in our MRS method compared with
      previous liver fat MRS studies is that we measured a plane of liver voxels at
      once rather than a single MRS voxel, yielding a reliable determination of liver
      fat content. RESULTS: Fat contents of 3.4-10% were observed in young GSD IXa
      patients, as compared with 0.5-0.9% in controls, these dropped to control levels
      in patients past age 40 (r = -0.82; P < 0.01). CONCLUSIONS: Liver fat content is
      increased in glycogen storage disease (GSD IXa) and normalizes with ageing.
      Assessing liver fat levels in this population is a novel and interesting concept.
      This could potentially enhance the understanding of liver function in that 20% of
      the population who has increased liver fat.

PMID- 17005291
TI  - Sensitivity study of human crystalline lens accommodation.
AB  - A nonlinear axisymmetric finite element method (FEM) analysis was employed to
      determine the critical geometric and material properties that affect human
      accommodation. In this model, commencing at zero, zonular traction on all lens
      profiles resulted in central lenticular surface steepening and peripheral surface
      flattening, with a simultaneous increase in central lens thickness and central
      optical power. An age-related decline in maximum zonular tension appears to be
      the most likely etiology for the decrease in accommodative amplitude with age.

PMID- 17005292
TI  - Combined chemoimmunotherapy of solid tumours: improving vaccines?
AB  - Cytotoxic chemotherapy not only affects the tumour but also targets dividing
      lymphocytes, the very cells required to develop an immune response. Hence, chemo-
      and immunotherapy have been seen as antagonistic. It is now clear that the way a
      chemotherapeutic drug kills a tumour cell determines how that dying cell
      interacts with the immune system and whether the interaction leads to an immune
      response. Chemotherapy also depletes regulatory T cells, potentially enhancing
      immune responses. Furthermore, lymphodepletion triggers homeostatic T cell
      reconstitution, creating new populations of pre-T cells that need education in
      the thymic environment. Post-chemotherapy immune system reconstitution may
      provide a unique opportunity for therapeutic intervention by shaping the
      repertoire towards reactivity to tumour antigens. An understanding of the
      underlying cellular and immunological events in both animal models and patients
      undergoing chemotherapy will guide decisions about which immunomodulatory
      approaches may be effective with different cytostatic drugs and hence to develop
      appropriate scheduling for integration of the treatment modalities.

PMID- 17005293
TI  - Particle engineering techniques for inhaled biopharmaceuticals.
AB  - Formulation of biopharmaceuticals for pulmonary delivery is faced with the
      challenge of producing particles with the optimal properties for deep lung
      deposition without altering the native conformation of these molecules.
      Traditional techniques such as milling are continuously being improved while
      newer and more advanced techniques such as spray drying, spray freeze drying and
      supercritical fluid technology are being developed so as to optimize pulmonary
      delivery of biopharmaceuticals. While some of these techniques are quite
      promising, some are harsh and impracticable. Method scale up, cost-effectiveness
      and safety issues are important factors to be considered in the choice of a
      technique. This paper reviews the presently developed techniques for particle
      engineering biopharmaceuticals.

PMID- 17005294
TI  - Phase II study of carboplatin, irinotecan, and thalidomide combination in
      patients with extensive stage small-cell lung cancer.

PMID- 17005295
TI  - Field test of a cross-injection scheme for stimulating in situ denitrification
      near a municipal water supply well.
AB  - A pilot-scale test of an in situ denitrification scheme was undertaken to assess
      an adaptation of the nutrient injection wall (NIW) technology for treating a deep
      (30-40 m) nitrate contamination problem (N-NO(-)(3) ~ 10-12 mg/L). The adaptation
      is called the Cross-Injection Scheme (CIS). It duplicates the NIW method without
      a wall; wells are installed and operated directly in the aquifer and high-flux
      zones of the aquifer are preferentially targeted for treatment. The test was
      conducted on the site of a municipal water supply well field, with the supply
      well pumping between 15-80 m(3)/h. Acetate was periodically injected into the
      aquifer between an injection-extraction well pair positioned across the normal
      direction of flow. The injected pulses were then permitted to move with the water
      toward the municipal wells, providing a carbon supply to drive the desired
      denitrification. The fate of nitrate, nitrite, acetate and sulphate were
      monitored at multilevel wells located between the injection location and the
      municipal wells. The acetate pulsing interval was approximately weekly (9 h
      injections), so that the system was operating passively 95% of the time. Previous
      work on the site has established that the highest solute fluxes were associated
      with a 1-3 m thick zone about 35 m below surface. This zone was found to respond
      to the acetate additions as a function of the municipal pumping rate and the
      carbon-to-nitrogen ratio (i.e., determined by the injected acetate
      concentration). Initially, acetate was injected just below the theoretical
      stoichiometric requirement for complete denitrification and nitrate disappearance
      was accompanied by nitrite production. Increasing the C:N ratio (doubling the
      acetate injection concentration) increased the removal of nitrate and diminished
      the occurrence of nitrite. Slowing the municipal pumping rate, with a C:N ratio
      of 1.2-1.6, resulted in complete nitrate attenuation with no nitrite production
      and no sulfate reduction. The experiment demonstrated that the CIS injection
      scheme is a viable option for the treatment of nitrate contamination in situ near
      high-capacity wells.

PMID- 17005297
TI  - Dietary behaviour of pregnant versus non-pregnant women.
AB  - This study investigates dietary behaviour and the perceived role of food for
      health of pregnant versus non-pregnant women. Data were collected between 15
      January 2003 and 15 March 2003 in Belgium. One hundred and forty-eight pregnant
      and 130 non-pregnant women aged between 20 and 40 years completed a self
      administered questionnaire about their dietary behaviour and nutritional
      attitudes. Both sub-samples match with respect to individual factors such as
      relevant socio-demographics and general food perceptions. Pregnant women report
      higher consumption of fruits, which results in a better score for fibre intake.
      They also report higher consumption of beef and dairy products, as well as a
      higher fat intake. No difference in fish consumption between pregnant and non
      pregnant women is observed. In line with recommendations, pregnant women report
      reduced consumption of food products with heightened safety-related risks, lower
      use of alcohol and tobacco, and safer food handling practices. Reduced intake of
      raw vegetables for food safety reasons is not compensated by higher intake of
      cooked vegetables. Pregnant women also report a lower frequency of moderate
      physical activity. Most differences in food choice by pregnant versus non
      pregnant women pertain to the avoidance of specific, potentially harmful food
      groups. A substantial share of pregnant women does not follow upon
      recommendations with respect to alcohol use and exposure to tobacco. Personal
      medical sources for pregnant women and personal social sources for non-pregnant
      women are reported as the most attended sources of diet-related information. The
      perceived role of food for health is not different between pregnant and non
      pregnant women, and there were no significant interaction effects between
      pregnancy and presence of children, which indicates that the observed differences
      in dietary behaviour can be attributed to the state of being pregnant.

PMID- 17005296
TI  - IQGAP and mitotic exit network (MEN) proteins are required for cytokinesis and re
      polarization of the actin cytoskeleton in the budding yeast, Saccharomyces
      cerevisiae.
AB  - In budding yeast the final stages of the cell division cycle, cytokinesis and
      cell separation, are distinct events that require to be coupled, both together
      and with mitotic exit. Here we demonstrate that mutations in genes of the mitotic
      exit network (MEN) prevent cell separation and are synthetically lethal in
      combination with both cytokinesis and septation defective mutations. Analysis of
      the synthetic lethal phenotypes reveals that Iqg1p functions in combination with
      the MEN components, Tem1p, Cdc15p Dbf20p and Dbf2p to govern the re-polarization
      of the actin cytoskeleton to either side of the bud neck. In addition
      phosphorylation of the conserved PCH protein, Hof1p, is dependent upon these
      activities and requires actin ring assembly. Recruitment of Dbf2p to the bud neck
      is dependent upon actin ring assembly and correlates with Hof1p phosphorylation.
      Failure to phosphorylate Hof1p results in the increased stability of the protein
      and its persistence at the bud neck. These data establish a mechanistic
      dependency of cell separation upon an intermediate step requiring actomyosin ring
      assembly.

PMID- 17005298
TI  - [A rare cause of acute abdominal pain].

PMID- 17005299
TI  - Primary influenza A virus infection induces cross-protective immunity against a
      lethal infection with a heterosubtypic virus strain in mice.
AB  - In order to assess the level of protection against a lethal influenza virus
      infection provided by a primary infection with a virus strain of another subtype,
      C57BL/6 mice were infected with the sublethal influenza virus X-31 (H3N2) and
      subsequently challenged with the lethal strain A/PR/8/34 (H1N1). The outcome of
      the challenge infection was compared with that in mice that did not experience an
      infection with influenza virus X-31 prior to the challenge infection. The X-31
      experienced mice cleared the infection with influenza virus A/PR/8/34 in an
      accelerated fashion, displayed less clinical signs and a reduction of lesions in
      the lungs resulting in improved survival rates of these mice compared to the
      naive mice. The improved outcome of the challenge infection with influenza virus
      A/PR/8/34 in the X-31 experienced mice correlated with priming for anamnestic
      virus-specific CD8(+) cytotoxic T lymphocyte (CTL) responses as was demonstrated
      by the detection of CTL specific for the H-2D(b) restricted NP(366-374) epitope
      that was shared by the influenza viruses X-31 and A/PR/8/34. Thus previous
      exposure to influenza A viruses affords partial protection against infection in
      the absence of virus-neutralizing antibodies specific for the hemagglutinin and
      the neuraminidase. The implications of these observations are discussed in the
      light of the current pandemic threat and development of vaccines that aim at the
      induction of virus-specific CTL.

PMID- 17005300
TI  - Noncytopathic bovine viral diarrhea virus can persist in testicular tissue after
      vaccination of peri-pubertal bulls but prevents subsequent infection.
AB  - The objectives of this research were to evaluate the risk of prolonged testicular
      infection as a consequence of vaccination of peri-pubertal bulls with a modified
      live, noncytopathic strain of BVDV and to assess vaccine efficacy in preventing
      prolonged testicular infections after a subsequent acute infection. Seronegative,
      peri-pubertal bulls were vaccinated subcutaneously with an approximate minimum
      immunizing dose or a 10x standard dose of modified-live, noncytopathic BVDV or
      were maintained as unvaccinated controls. Forty-nine days after vaccination, all
      bulls were intranasally inoculated with a noncytopathic field strain of BVDV.
      Semen and testicular biopsies collected after vaccination and challenge were
      assayed for BVDV using virus isolation, reverse transcription-nested PCR, or
      immunohistochemistry and the identity of viral strains was determined by
      nucleotide sequencing of PCR products. The vaccine strain of BVDV was detected in
      testicular tissue of vaccinated bulls as long as 134 days after immunization.
      Prolonged testicular infections with the challenge strain were detected only in
      unvaccinated bulls as long as 85 days after challenge. Whereas vaccination caused
      prolonged testicular infection in some bulls, it did prevent subsequent infection
      of testicular tissue with the challenge strain. This research demonstrates that
      subcutaneous vaccination of naive, peri-pubertal bulls with a noncytopathic,
      modified-live strain of BVDV can result in prolonged viral replication within
      testicular tissue. The risk for these prolonged testicular infections to cause
      venereal transmission of BVDV or subfertility is likely to be low but requires
      further investigation.

PMID- 17005301
TI  - World Health Organisation definition of "radiologically-confirmed pneumonia" may
      under-estimate the true public health value of conjugate pneumococcal vaccines.
AB  - The public health benefit of conjugate pneumococcal vaccine (PCV) in preventing
      pneumonia would only be appreciated if the tool used for measuring "pneumococcal
      pneumonia" had good sensitivity. Exploratory studies in South Africa indicate
      that the sensitivity of "radiologically-confirmed pneumonia" (CXR-AC)
      underestimates the burden of pneumococcal pneumonia prevented by PCV by as much
      as 63%. The use of alternate markers such as C-reactive protein enhance the
      ability of measuring the burden of pneumonia preventable by PCV. A broadened
      definition of "pneumococcal pneumonia" which includes episodes of pneumonia
      associated with CXR-AC and those associated with an abnormal chest radiograph
      other than CXR-AC associated with a CRP of > or =40mg/l should be considered an a
      priori outcome in future PCV efficacy trials.

PMID- 17005302
TI  - Identification of pentadecapeptide mimicking muramyl peptide.
AB  - We used monoclonal antibody, generated against N-acetylglucosaminyl-beta1-4-N
      acetylmuramyl-alanyl-D-isoglutamine (GMDP), and phage display libraries of random
      peptides to select for oligopeptides, that mimic GMDP in their biological
      activity. Selected phage clones displayed a peptide RVPPRYHAKISPMVN (called RN
      peptide) on their surface. This peptide was synthesized. RN-peptide was shown to
      augment the antibody response to ovalbumin in mice while the peptide was non
      immunogenic and non-pyrogenic. We also characterized adjuvant activity of 14-, 10
      and 7-mer analogs of RN-peptide truncated at the C-terminus and found them to be
      active. Because both carbohydrate and peptide fragments are critical for the
      biological activity of muramyl peptides, the results indicate that RN-peptide
      mimicks the spatial structure of intact GMDP.

PMID- 17005303
TI  - Optimisation of secretion of recombinant HBsAg virus-like particles: Impact on
      the development of HIV-1/HBV bivalent vaccines.
AB  - The hepatitis B surface antigen (HBsAg) assembles into virus-like particles
      (VLPs) that can be used as carrier of immunogenic peptides for the development of
      bivalent vaccine candidates. It is shown here that by respecting certain
      qualitative features of mammalian preS1 and preS2 protein domains upstream of
      HBsAg, foreign sequences can be inserted in their place while maintaining
      efficient secretion of VLPs. A polyepitope bearing HIV-1 epitopes restricted to
      the HLA-A*0201 class I allele was optimised for secretion as an HBsAg fusion
      protein by counterbalancing the generally hydrophobic class I epitopes with
      hydrophilic spacers, eliminating epitopes bearing cysteine residues, limiting the
      number of internal methionine residues to a minimum and adopting Homo sapiens
      codon usage. The optimised HIV-1 polyepitope-HBsAg recombinant protein with up to
      138 residues assembled into efficiently secreted recombinant VLPs. DNA
      immunisation in HLA-A*0201 and HLA-A*0201/HLA-DR1 transgenic mice resulted in the
      recovery of humoral response against the carrier and enhanced levels of HIV-1
      specific CD8(+) T lymphocyte activation. Efficient self-assembly of recombinant
      HBsAg VLPs opens up the possibility of making efficient bivalent HBV/HIV vaccine
      candidates, which is particularly apposite given that the two viruses are
      frequently associated.

PMID- 17005304
TI  - Persistence of seroprotection 10 years after primary hepatitis A vaccination in
      an unselected study population.
AB  - Hepatitis A vaccines have been demonstrated to be highly immunogenic.
      Mathematical models have predicted antibodies to persist for at least 20-25
      years. Most of these studies have been conducted in young and healthy study
      populations. We aimed to evaluate long-term immunity 10 years following complete
      primary immunization according to a 3-dose schedule (Havrix 720 El.U at months 0,
      1, 6-12) in an adult and unselected study population. In total, 999 (98.3%) of
      1016 vaccinees (mean age 54.7+/-S.D. 13.0), tested 10 years after primary
      vaccination, still had protective antibody levels (> or = 10 mIU/ml) as measured
      by ELISA. An anti-HAV titer cut off level of 11,400 mIU/ml was calculated to
      differentiate between vaccine-induced and infection-induced titer levels. The
      vaccine-induced geometric mean titer (GMT) was 406.1 mIU/ml (95% CI: 369.2-446.7
      mIU/ml), showing an age-related trend, the 10-years seroprotection rate (SPR) was
      97.9%. Females exhibited significantly higher GMTs than male vaccinees (p<0.001).
      The only parameter predicting a titer below 10 mIU/ml 10 years after vaccination
      was the body mass index (p=0.001). This study confirms that protection following
      primary hepatitis A vaccination persists for more than 10 years.

PMID- 17005305
TI  - Effects of exogenous crosslinking on in vitro tensile and compressive moduli of
      lumbar intervertebral discs.
AB  - BACKGROUND: Collagen crosslinks may play a vital role in preventing ongoing disc
      degeneration. Age-accumulating crosslinks have been thought to increase
      brittleness and reduce fatigue resistance. However recent studies have
      demonstrated increases in fatigue resistance, joint stability and nutritional
      flow properties resulting from crosslink augmentation. In this study, multi
      directional moduli of bovine lumbar intervertebral discs were measured in vitro,
      including circumferential tension, radial compression, axial tension, and axial
      compression in control and crosslinked specimens. METHODS: Four types of annulus
      fibrosus specimens were dissected from control and crosslinked discs. Cross
      sectional areas were measured using a non-contact laser measurement system and
      then four separate mechanical tests were conducted using a materials testing
      machine with custom-made loading fixtures. FINDINGS: The circumferential
      specimens demonstrated the highest moduli in both low stiffness and linear
      elastic regions. After a crosslink treatment, the modulus increased more in
      circumferential tension compared to axial tension and more in axial compression
      compared to radial compression. Other tensile properties had higher increases in
      circumferential tension compared to axial tension after crosslinking.
      INTERPRETATION: Assuming form follows function, circumferential tension is the
      predominant type of stress experienced by non-degenerated annulus fibrosus. The
      anisotropic mechanical properties of the annulus fibrosus is non-uniformly
      affected by crosslink augmentation. Dominant effects were in the directions with
      greater inherent stiffnesses. These results suggest some beneficial effects of
      crosslink augmentation on the mechanical properties of the annulus fibrosus:
      increase in ultimate strength, yield strength, toughness, and modulus in the
      principal stress directions.

PMID- 17005306
TI  - [Arteriovenous malformations: clinical aspects and evolution].
AB  - Arteriovenous malformations are rare high-flow malformations. As other
      malformations, they are present at birth but may remain quiescent for many years;
      their flow may speed up quickly consequently on an infection, traumatism or
      modification of the hormonal climate. A "nidus" appears in the heart of the
      malformation which acts as a real "turbo" on the blood flow; vascular shunts
      appear creating ulcerations (vascular steal phenomenon); cardiac failure may be
      observed. Among all vascular anomalies, arteriovenous malformation is the most
      dangerous in its evolution which may be fatal. Its control requires prudence and
      skill.

PMID- 17005307
TI  - [Medical and surgical treatment of venous malformations].
AB  - Treatment of venous malformations (VM) is difficult as these lesions are ill
      defined and can infiltrate tissues. Moreover, no specific treatment related to
      their etiopathogenesis exists. Currently, VM can be treated conservatively or
      medically and, more aggressively with either sclerotherapy, or surgical
      resection. A multidisciplinary approach is needed to obtain the best result with
      minimal complications. Surgical resection, complete or partial, plays an
      important role in the treatment of symptomatic VM. In case of extensive VM, all
      techniques of plastic surgery are indicated.

PMID- 17005308
TI  - [Venous malformations and coagulopathy].
AB  - Activation of the coagulation process is frequently encountered in patients with
      venous vascular malformations and results in the local formation of clots and the
      consumption of components of the coagulation process (platelets, clotting
      factors). This activation accounts for multiple biological abnormalities such as
      the elevation of the D-dimers, reduction of fibrinogen and platelets count and
      less frequently a local intravascular coagulation (LIC). This process seems to be
      responsible for the local painful symptoms. In case of LIC, bleeding
      complications may be observed. Therapeutically, antithrombotic treatment with low
      molecular weight heparin can improve the local coagulopathy with beneficial
      effects on blood tests disturbances, pain and bleeding tendency.

PMID- 17005309
TI  - [Vascular tumours and malformations, classification, pathology and imaging].
AB  - The understanding of vascular anomalies (vascular tumours and vascular
      malformations) was obscured, for a long time, by confusion and uncertainties in
      nosology and terminology. The International Society for the Study of Vascular
      Anomalies (ISSVA) recently adopted a classification scheme, clearly separating
      vascular tumours (hemangiomas of different types) which result from active cell
      proliferation, from vascular malformations, which are inborn defects in vascular
      morphogenesis. These two types of lesions have different clinical behaviour and
      require different diagnostic and therapeutic strategies. The most frequent
      vascular tumour is infantile hemangioma. Its clinical aspects and evolution are
      well-known. New data have been recently obtained concerning the phenotype of
      tumour cells and its histogenesis. Of the numerous new vascular tumours, which
      have been recently described, only the congenital hemangiomas, the vascular
      tumours associated with the Maffucci syndrome and the tumours that may be
      complicated by a profound thrombocytopenia (Kasabach and Merritt phenomenon) will
      be considered. Vascular malformations can be classified according to the
      vessel(s) types they are composed of. A classification table is presented,
      separating the malformations of vascular trunks from tissular malformations which
      are more intimately embedded in the surrounding tissues. The different syndromes
      associated with vascular anomalies take also place in this table. The clinical,
      imaging and histological aspects of the most frequent malformations (capillary,
      venous, lymphatic and arteriovenous) are presented. This classification intend to
      clarify the nosology and terminology of the complex field of vascular tumours and
      malformation and to offer a common language to the different physicians and
      specialists contributing, preferably with a interdisciplinary approach, to the
      diagnosis and treatment of these difficult lesions.

PMID- 17005310
TI  - [Port wine stains and laser treatments].
AB  - Port wine stains correspond to cutaneous congenital capillary dysplasias and are
      undergoing broad clinical appearances as far as size, colour, and anatomical
      areas are concerned together with several possible associations to other vascular
      pathology. Laser treatment started by the end of the 70's with, at that time
      moderate scientific production, followed by a very "explosive" period till mid
      90's, leading to a progressive decrease till today. Therefore, everything has
      been reported several times and, in some occasions with some kind of artlessness
      and/or without follow-up. Author will try in this paper to report a 25 years
      experience, with as much objectivity as possible.

PMID- 17005311
TI  - [Port wine stains or capillary malformations: surgical treatment].
AB  - Capillary malformations do not demand mostly any therapeutics. For aesthetic
      reasons, family or child can demand a treatment to ease even to remove the
      unsightly character of the lesion. In this context, the means employees must be
      simple and not engender aftereffects more unaesthetic than the lesion. The pulsed
      dye laser fulfils perfectly this conditions by improving the color of the lesion
      without touching the texture of the skin. However it's a treatment requiring many
      sessions over 2-3 years. Surgery keeps an interest for the treatment of capillary
      malformations resistant to laser (in particular on the limbs) or to treat soft
      tissues hyperplasia met in certain cervicofacial locations. The surgery uses the
      whole techniques of plastic surgery classified from the most simple to the most
      complicated: excision-suture in one time or iterative, excision and coverage by a
      skin graft, use of skin expansion techniques with local flaps.

PMID- 17005313
TI  - Echocardiographic observations during in-hospital cardiopulmonary resuscitation.

PMID- 17005312
TI  - Adaptive changes in acetylcholinesterase gene expression as mediators of recovery
      from chemical and biological insults.
AB  - Both organophosphate (OP) exposure and bacterial infection notably induce short-
      and long-term cholinergic responses. These span the central and peripheral
      nervous system, neuromuscular pathway and hematopoietic cells and involve over
      expression of the "readthrough" variant of acetylcholinesterase, AChE-R, and its
      naturally cleavable C-terminal peptide ARP. However, the causal involvement of
      these changes with post-exposure recovery as opposed to apoptotic events remained
      to be demonstrated. Here, we report the establishment of stably transfected cell
      lines expressing catalytically active human "synaptic" AChE-S or AChE-R which are
      fully viable and non-apoptotic. In addition, intraperitoneally injected synthetic
      mouse ARP (mARP) elevated serum AChE levels post-paraoxon exposure. Moreover,
      mARP treatment ameliorated post-exposure increases in corticosterone and
      decreases in AChE gene expression and facilitated earlier retrieval of motor
      activity following both paraoxon and lipopolysaccharide (LPS) exposures. Our
      findings suggest a potential physiological role for overproduction of AChE-R and
      the ARP peptide following exposure to both chemical warfare agents and bacterial
      LPS.

PMID- 17005314
TI  - The Resuscitation Greats: Thomas Cecil Gray CBE KCSG FRCP FRCS FRCA and Gordon
      Jackson Rees FRCA FRCP FRCPCH: major contributors to post-resuscitation care.

PMID- 17005315
TI  - Bird distributions relative to remotely sensed habitats in Great Britain: towards
      a framework for national modelling.
AB  - This paper develops a comprehensive and objective picture of bird distributions
      relative to habitats across Britain. Bird species presence/absence data from an
      extensive field survey and habitat data from the remotely sensed UK Land Cover
      Map 2000 were analysed in 36,920 tetrads (2 kmx2 km) across Britain (a 65% sample
      of Britain's c. 240,000 km2). Cluster analysis linked birds to generalised
      landscapes based on distinctive habitat assemblages. Maps of the clusters showed
      strong regional patterns associated with the habitat assemblages. Cluster
      centroid coordinates for each bird species and each habitat were combined across
      clusters to derive individualised bird-habitat preference indices and examine the
      importance of individual habitats for each bird species. Even rare species and
      scarce habitats showed successful linkages. Results were assessed against
      published accounts of bird-habitat relations. Objective corroboration strongly
      supported the associations. Relatively scarce coastal and wetland habitats proved
      particularly important for many birds. However, extensive arable farmland and
      woodland habitats were also favoured by many species, despite reported declines
      in bird numbers in these habitats. The fact that habitat-specialists do not or
      cannot move habitat is perhaps a reason for declining numbers where habitats have
      become unsuitable. This study showed that there are unifying principles
      determining bird-habitat relations which apply and can be quantified at the
      national scale, and which corroborate and complement the cumulative knowledge of
      many and varied surveys and ecological studies. This 'generality' suggests that
      we may be able, reliably and objectively, to integrate and scale up such
      disparate studies to the national scale, using this generalised framework. It
      also suggests the potential for a landscape ecology approach to bird-habitat
      analyses. Such developments will be important steps in building models to develop
      and test the sustainable management of landscapes for birds.

PMID- 17005316
TI  - The clinical potential of pretreatment serum testosterone level to improve the
      efficiency of prostate cancer screening.
AB  - OBJECTIVES: The aim of the present study was to evaluate the clinical value of
      the pretreatment serum testosterone (T) level as a potential predictor of
      prostate cancer risk in screening for prostate cancer. MATERIALS AND METHODS: The
      subjects were 420 patients suspected of having prostate cancer who underwent
      prostate biopsy, and whose pretreatment T levels were recorded. We checked for
      association between the presence of prostate cancer and the following clinical
      factors: pretreatment serum T level, age, pretreatment prostate-specific antigen
      (PSA) level, digital rectal examination findings, ratio of free to total PSA,
      prostate volume, and PSA density (PSAD). RESULTS: Overall, there was no
      significant difference in mean pretreatment T level between patients diagnosed
      with cancer (3.9+/-2.4 ng/ml) and patients diagnosed with benign prostate disease
      (BPD; 3.7+/-1.7 ng/ml); diagnosis was based on prostate biopsy. However, among
      patients with PSA <10 ng/ml, the pretreatment T level was significantly higher in
      patients diagnosed with prostate cancer (4.2+/-2.6 ng/ml) than in patients
      diagnosed with BPD (3.6+/-1.4 ng/ml) (p=0.007); a similar trend was observed
      among patients with PSAD <0.15 ng/ml/cc. Multivariate analysis indicated that
      pretreatment T level was an independent significant predictor of positive
      prostate biopsy (p=0.020). Additionally, the serum T level was significantly
      lower in patients with a Gleason score >or=7 (3.7+/-2.1 ng/ml) versus a score <7
      (4.2+/-1.7 ng/ml) (p=0.030). Also, serum T levels were significantly higher in
      well-differentiated prostate cancer (4.8+/-2.1 ng/ml) versus moderately
      differentiated (3.8+/-1.3 ng/ml) or poorly differentiated (3.7+/-1.4 ng/ml)
      (p<0.01). CONCLUSIONS: Among relatively low-risk patients, serum T level was an
      independent significant predictor of positive prostate biopsy, suggesting that
      the efficiency of prostate cancer screening can be improved by including
      measurement of serum T level.

PMID- 17005317
TI  - Ureteroscopic laser approach in recurrent ureteropelvic junction stenosis.
AB  - OBJECTIVES: Endourological procedures are widely used for treating ureteropelvic
      junction (UPJ) obstruction. Our aim was to establish the value of using laser
      retrograde endopyelotomy (REP) in cases with recurrence. MATERIALS AND METHODS:
      Between November 2000 and June 2005 we performed 30 REPs in recurrent UPJ
      obstruction with grades 3 and 4 hydronephrosis (failed pyeloplasty, 17 cases;
      failed endopyelotomy, 13 cases). Our series was characterized by absence of renal
      calculi, stenosis length<2 cm, and absence of massive hydronephrosis. We used
      semirigid and flexible endoscopic equipment (Wolf and Storz) and holmium:YAG
      laser. In 11 cases, an indwelling double J was placed for 2 wk. An indwelling
      pyelostent 8/12 F was postoperatively placed for 8 wk. RESULTS: All cases were
      evaluated at 6, 12, and 18 mo. Ultrasonography and urography were the main follow
      up investigations. At 6 mo, we found normal UPJ and pyelocaliceal system in 9
      cases (30%); a reduction of the hydronephrosis degree with normal UPJ in 4 cases
      (13.3%); and no changes of the hydronephrosis degree in 17 cases (56.6%), but
      with large UPJ passage in 13 of the 17 cases (76.5%). REP success did not
      correlate with the degree of hydronephrosis. The success rate after 18 mo was
      83.3%. Patients experienced minor complications. The mean follow-up period was 31
      mo (range: 18-52 mo). CONCLUSIONS: REP may represent an efficient minimally
      invasive technique in recurrent UPJ stenosis, with a reduced rate of
      complications, short period of hospitalization, and good anatomical and
      functional results.

PMID- 17005318
TI  - H-CORE: enabling genome-scale Bayesian analysis of biological systems without
      prior knowledge.
AB  - The Bayesian network is a popular tool for describing relationships between data
      entities by representing probabilistic (in)dependencies with a directed acyclic
      graph (DAG) structure. Relationships have been inferred between biological
      entities using the Bayesian network model with high-throughput data from
      biological systems in diverse fields. However, the scalability of those
      approaches is seriously restricted because of the huge search space for finding
      an optimal DAG structure in the process of Bayesian network learning. For this
      reason, most previous approaches limit the number of target entities or use
      additional knowledge to restrict the search space. In this paper, we use the
      hierarchical clustering and order restriction (H-CORE) method for the learning of
      large Bayesian networks by clustering entities and restricting edge directions
      between those clusters, with the aim of overcoming the scalability problem and
      thus making it possible to perform genome-scale Bayesian network analysis without
      additional biological knowledge. We use simulations to show that H-CORE is much
      faster than the widely used sparse candidate method, whilst being of comparable
      quality. We have also applied H-CORE to retrieving gene-to-gene relationships in
      a biological system (The 'Rosetta compendium'). By evaluating learned information
      through literature mining, we demonstrate that H-CORE enables the genome-scale
      Bayesian analysis of biological systems without any prior knowledge.

PMID- 17005319
TI  - Sanguinarine induces apoptosis of human pancreatic carcinoma AsPC-1 and BxPC-3
      cells via modulations in Bcl-2 family proteins.
AB  - Pancreatic cancer is associated with low responsiveness to conventional
      chemotherapies and its incidence nearly equals its death rate. This warrants the
      development of novel mechanism-based approaches for the management of pancreatic
      cancer. This study was designed to determine the potential of sanguinarine, a
      plant alkaloid known to possess strong antimicrobial, anti-inflammatory, and
      antioxidant activities, against human pancreatic carcinoma cells. Employing human
      pancreatic carcinoma AsPC-1 and BxPC-3 cells, we specifically evaluated the pro
      apoptotic and cell cycle deregulatory effects of sanguinarine and evaluated the
      involvement of Bcl-2 family proteins and p53 as the mechanism of the biological
      effects of sanguinarine. Our data demonstrated that sanguinarine (at low
      concentrations of 0.1-10 microM; for 24 h) treatment to AsPC-1 and BxPC-3 cells
      resulted in a dose dependent (i) inhibition of viability and growth, (ii) colony
      formation ability, (iii) induction of apoptosis, and (iv) G0-G1 phase cell cycle
      arrest. Further, sanguinarine-treatment to AsPC-1 and BxPC-3 cells resulted in a
      dose dependent (i) increase in pro-apoptotic Bax, Bid and Bak proteins; (ii)
      decrease in anti-apoptotic Bcl-2 and Bcl-X(L) proteins; and (iii) decrease in p53
      with an increase in its phosphorylation. Based on our study, we suggest that
      sanguinarine may be developed as an agent for the management of pancreatic
      cancer. Indeed, more in depth studies both in vitro as well as in vivo in
      appropriate relevant animal models are needed to strengthen this suggestion.

PMID- 17005320
TI  - Catalytic decolorization of azo-stuff with electro-coagulation method assisted by
      cobalt phosphomolybdate modified kaolin.
AB  - The new catalytic decoloration of C.I. Acid Red 3R with electro-coagulation (EC)
      method assisted by cobalt phosphomolybdate modified kaolin has been studied. The
      result showed that this process could effectively remove the C.I. Acid Red 3R
      contained in wastewater and its color removal efficiency could reach up to 98.3%
      in 7 min. The kinetics of the catalytic decolorization of Acid Red 3R was also
      studied. The decolorization reaction order was dependent on the initial
      concentration [R](0) with respect to the concentration of C.I. Acid Red 3R. At
      lower [R](0) the order was first, which then decreases with increasing [R](0).
      The operating parameters such as initial pH, current density and temperature were
      also investigated. A possible reaction mechanism was proposed.

PMID- 17005321
TI  - Dissociation of grey and white matter reduction in spinocerebellar ataxia type 3
      and 6: a voxel-based morphometry study.
AB  - The aim of this study was to examine the different patterns of cerebellar and/or
      brainstem atrophy in spinocerebellar ataxia (SCA) type 3 and 6. Eighteen patients
      (SCA3 n=9, SCA6 n=9) and 15 healthy volunteers were studied. Voxel-based
      morphometry (VBM) was applied to segmented grey matter (GM) and white matter (WM)
      of high-resolution T1-weighted brain volumes of each group. We found reduction of
      grey matter in the pons as well as in the vermis in SCA3 as compared to control
      subjects. In SCA6 significant grey matter loss was found in hemispheric lobules
      bilaterally as well as in the vermis. White matter analysis revealed significant
      changes in SCA3, especially in the pons, in the white matter surrounding the
      dentate nucleus (DN) and in the cerebellar peduncles, whereas no significant
      white matter reduction was found in SCA6 patients. Our results demonstrate
      different patterns of grey and white matter affection detected by magnetic
      resonance imaging (MRI) in SCA3 and SCA6 patients, confirming the pathological
      concept of cortical cerebellar atrophy in SCA6. In contrast, SCA3 represents a
      form of ponto-cerebellar atrophy with predominant affection of pontine nuclei and
      fibre tracts.

PMID- 17005322
TI  - Semantic retrieval of spoken words with an obliterated initial phoneme in a
      sentence context.
AB  - Perception of a phoneme may occur even when the speech sound is missing (e.g.,
      when an extraneous noise replaces the sound). This phenomenon, called phonemic
      restoration, has been observed to depend on the type of distortion. It requires a
      replacing sound that provides acoustic input to the auditory system, since the
      restoration has not been found when a speech sound was replaced by silence. We
      examined the brain activation underlying speech processing when the word's
      initial phoneme was completely replaced by a silent gap. Event-related potentials
      (ERPs) and reaction times (RTs) were measured as indicators of semantic
      processing of sentence final words. Slower voice onset times during repetition of
      the manipulated words as compared to normal words indicated increased difficulty
      in retrieving their meaning. The N400, which is related to the increased demands
      of the semantic integration of words, was elicited by less expected words as
      compared to highly expected ones. For manipulated words, the N400 was elicited at
      the same latency than for normal words, with respect to the onset of the
      remaining word fragment. The amplitude of the N400 was not increased, nor did it
      last longer, thereby indicating successful retrieval of the word's meaning based
      on the semantic context and remaining phonetic information. Thus, semantic
      retrieval does not seem to require the word's initial phoneme to be present in a
      sentence context. The results suggest that both context-driven expectancy (top
      down) and stimulus-driven processes (bottom-up) are utilized in word processing
      and contribute to the overall N400 response.

PMID- 17005323
TI  - Semi-nested PCR detection of Babesia orientalis in its natural hosts
      Rhipicephalus haemaphysaloides and buffalo.
AB  - Babesiosis has recently been recognized as an emerging infectious disease of
      buffalo in China. In order to investigate the epidemiology and enzootic potential
      of this parasite in Hubei province, we sought to develop a semi-nested PCR to
      detect Babesia orientalis in buffalo and the potential tick vector-Rhipicephalus
      haemaphysaloides by amplifying a specific 257bp fragment of B. orientalis 18S
      rRNA gene. The practical limit of detection showed that it had high sensitivity
      and an approximate parasitemia of 0.00000012% was detected by the PCR system. The
      blood samples of 121 asymptomatic buffaloes collected from four babesia endemic
      counties and that of 71 asymptomatic buffaloes collected from three babesia free
      counties in Hubei province of China were examined for the presence of B.
      orientalis using both Wright-Giemsa stained blood smear and semi-nested PCR.
      Microscopic examination revealed that 5/121 animals were positive, whereas 24/121
      animals were positive by the semi-nested PCR assay. Of 378 ticks (R.
      haemaphysaloides) collected from buffaloes and examined by the semi-nested PCR,
      35 were positive. The results showed that the semi-nested PCR was a useful method
      to investigate the epidemiology of buffalo babesiosis (B. orientalis), which is
      widely distributed in Hubei province, China.

PMID- 17005324
TI  - Burns first aid information on the Internet.
AB  - The Internet is an increasingly important source of health-related information.
      However, the growth of the Internet and its use as a medical delivery tool should
      be viewed with caution. One of the key concerns is that although the volume of
      information is huge, the quality, accuracy and completeness of the information is
      questionable. The aim of this study was to evaluate burns first aid information
      on the Internet. The search term used was "first aid for burns" and the first 25
      hits from each search engine were analysed by one of the observers. We gathered
      basic information on the web sites--such as the country of origin, language in
      which the information was offered, accessibility, relevance and whether the site
      was commercial, organisational or academic. Quality and technicality of the web
      sites were assessed and scored. The mean quality score was 4.7/15 (31.5%) The
      mean technical score was 6.1 of 12 (51.1%). When the total score was categorised
      by percentage, none of the web sites ranked in the excellent category, 1 was very
      good, 4 were good, 6 were fair and the majority, 36, were poor. Based on the
      quality score only, two web sites were in the excellent category and two were
      very good. For technicality one web site was excellent and three were very good.
      This study has shown first aid information on the Internet is largely of poor
      quality, that the technical information provided is inadequate and that the sites
      include a significant amount of grossly inaccurate information. The few sites
      that contain excellent technical information make up a very small proportion of
      what is available. Therefore, the average Internet user may not encounter these
      resources, instead gaining knowledge from sites of questionable value.

PMID- 17005325
TI  - Detecting genetic predisposition for complicated clinical outcomes after burn
      injury.
AB  - Sepsis, septic shock and organ failure are common among patients with moderate to
      severe burns. The inability of demographic and clinical factors to identify
      patients at high risk for such complications suggests that genetic variation may
      influence clinical outcome. Moreover, the genetic predisposition to death from
      infection has been estimated to be greater than for cardiovascular disease or
      cancer . While it is widely accepted that genetic factors influence many complex
      disease processes, controversy has emerged regarding the most appropriate methods
      for detection and even the validity of many published allelic associations . This
      article will review the few studies of genetic predisposition that have been
      conducted in the setting of burn injury, then discuss some of the obstacles and
      potential approaches for the discovery of additional allelic associations.

PMID- 17005326
TI  - Goats, germs, and fever: Are the pyrin mutations responsible for familial
      Mediterranean fever protective against Brucellosis?
AB  - Mutations in the MEFV gene are highly prevalent in the Middle East and
      Mediterranean basin, with carrier rates of up to 1:3 in some populations. More
      than 50 mutations in the MEFV gene have been described. The high prevalence,
      multiple mutations, and geographic localization to the Middle East suggest a
      positive selection advantage for the abnormal gene operating in this area over
      the last several thousand years. To date, no satisfactory explanation of this
      phenomenon has been made. Rather, many harmful effects of these mutations have
      been described. MEFV gene mutations cause familial Mediterranean fever in
      homozygotes, a disease associated with recurrent febrile inflammatory episodes,
      and death from renal failure and amyloidosis. Heterozygotes with MEFV mutations
      are predisposed to premature coronary disease, and rheumatologic conditions such
      as Behcet's disease. MEFV mutations do not appear to protect against
      tuberculosis. Brucellosis is still highly endemic in the Middle East because of
      the traditional reliance for meat and dairy production on goats and sheep, the
      major vectors for this zoonosis. Brucellosis causes a prolonged febrile illness
      lasting for months and even years, and it may have exacted a major toll among
      Bronze Age peasant populations in the Middle East. The gene product for MEFV,
      pyrin, normally inhibits interleukin-1beta production. Mutations in MEFV result
      in a pro-inflammatory state, with a Th1 polarization and high levels of
      interferon-gamma. This may actually be protective against intracellular pathogens
      such as brucellosis. The possible heterozygote advantage of MEFV mutations
      against brucellosis may therefore be a balanced polymorphism, analogous to the
      protective effect against malaria that maintains high levels of sickle cell trait
      in sub-Saharan Africa.

PMID- 17005327
TI  - Lone atrial fibrillation: Pathologic or not?
AB  - Atrial fibrillation risk has been strongly associated with increasing age and
      visceral obesity. These characteristics are strongly associated with diabetes,
      decreased heart rate variability, and chronic inflammation. Lone atrial
      fibrillation (LAF) on the other hand exhibits a predilection for the physically
      fit and the middle aged, especially males. Given these opposing features it is
      postulated that pathologic AF is due to cardiac fibrosis and other age related
      changes while LAF is due to physiologic neurohormonal changes related to
      autonomic tone, insulin sensitivity, and electrolyte imbalance and that
      pathologic AF and LAF can be reliably differentiated via an anthropometric
      approach using weight, height, hip, and waist measurements. An anthropometric
      study is undertaken from an LAF database to test this hypothesis. Such
      individuals in addition to being younger and predominantly male appear to be
      taller with less central adiposity vs. those with pathologic AF. The
      ramifications of these findings with respect to insulin resistance, sympathetic
      tone, inflammation and hypertension, often associated with pathologic atrial
      fibrillation, are discussed. Speculation is drawn about possible etiologic link
      with mitral valve prolapse, which is commonly encountered in the tall and thin
      and which shares multiple clinical features with LAF.

PMID- 17005328
TI  - Memantine as a neuroprotective agent in early phases of psychosis.

PMID- 17005330
TI  - Annotation, nomenclature and evolution of four novel homeobox genes expressed in
      the human germ line.
AB  - The homeobox genes comprise a large gene superfamily characterised by a conserved
      DNA motif encoding the homeodomain. Most homeodomain proteins function as
      transcription factors, and many have important roles in embryonic development and
      cell differentiation. Here we describe, annotate and name four novel homeobox
      genes in the human genome: ARGFX, DPRX, TPRX1 and DUXA. Each has generated
      multiple retrotransposed (processed) pseudogenes; these are reliable indicators
      of germ-line expression because only in germ-line cells can retrotransposition
      result in inheritance to the next generation. The retrotransposed sequences were
      exploited here as a novel means to deduce exon-intron boundaries. All four novel
      genes show accelerated rates of protein sequence evolution. This fast rate of
      sequence change may be connected with roles in human reproductive biology.
      Deducing the evolutionary origins of these genes is not straightforward, but we
      propose that TPRX1, DPRX and DUXA are highly divergent derivatives of the CRX
      gene, itself a member of the Otx homeobox gene family.

PMID- 17005329
TI  - Regardless of psychiatric severity the addition of contingency management to
      standard treatment improves retention and drug use outcomes.
AB  - The relationship between psychiatric severity and substance use disorders
      treatment outcome was assessed in 393 individuals who received either standard
      treatment or standard treatment plus contingency management. The sample was
      divided into groups of low, moderate, and high psychiatric severity based upon
      baseline Addiction Severity Index psychiatric composite scores. Participants in
      the high psychiatric severity group reported a greater prevalence of psychiatric
      hospitalization, psychiatric medications, and suicide attempts, as well as poorer
      baseline psychosocial functioning. In terms of treatment outcome, a significant
      interaction between psychiatric severity and treatment modality was found in
      relation to treatment retention. Participants in the standard treatment condition
      were more likely to dropout of treatment earlier as psychiatric severity
      increased, while retention was similar across the psychiatric severity groups in
      the contingency management condition. Psychiatric severity was not linked to
      longest duration of abstinence achieved during treatment or adherence with
      contingency management procedures. Overall, these findings suggest contingency
      management is an efficacious and appropriate intervention for substance use
      disordered individuals across a range of psychiatric problems.

PMID- 17005331
TI  - Developmental expression pattern of histone H4 gene associated to DNA synthesis
      in the endoparasitic platyhelminth Mesocestoides corti.
AB  - In higher eukaryotes, histone gene expression is coupled to DNA replication
      during the S-phase of the cell cycle. This coupling is primarily controlled at
      the transcriptional level. Considering the basal phylogenic position of
      platyhelminthes in the bilateria phylum, we have cloned a partial sequence of the
      histone H4 gene of Mesocestoides corti and studied its expression during the post
      larval development of this endoparasitic platyhelminth. In in vitro trypsin
      induced tetrathyridia development to segmented adult worm, we found that histone
      H4 is expressed concomitantly with DNA synthesis throughout all stages of
      development. DNA synthesis and histone H4 mRNA levels were sharply increased at
      24 h after inducing development. Afterwards, tetrathyridia grew in length from
      days 4 to 12 of development as proliferative cells gradually increased in number.
      Consequently, during this period of development histone H4 mRNA levels were
      upregulated. Taken together these results suggest that a replication-dependent
      expression pattern of histone H4 occurs in ancient bilateria, such as
      platyhelminthes, as previously observed in higher eukaryotes.

PMID- 17005332
TI  - The evolution of retrotransposon regulatory regions and its consequences on the
      Drosophila melanogaster and Homo sapiens host genomes.
AB  - It has now been established that transposable elements (TEs) make up a variable,
      but significant proportion of the genomes of all organisms, from Bacteria to
      Vertebrates. However, in addition to their quantitative importance, there is
      increasing evidence that TEs also play a functional role within the genome. In
      particular, TE regulatory regions can be viewed as a large pool of potential
      promoter sequences for host genes. Studying the evolution of regulatory region of
      TEs in different genomic contexts is therefore a fundamental aspect of
      understanding how a genome works. In this paper, we first briefly describe what
      is currently known about the regulation of TE copy number and activity in
      genomes, and then focus on TE regulatory regions and their evolution. We restrict
      ourselves to retrotransposons, which are the most abundant class of eukaryotic
      TEs, and analyze their evolution and the subsequent consequences for host
      genomes. Particular attention is paid to much-studied representatives of the
      Vertebrates and Invertebrates, Homo sapiens and Drosophila melanogaster,
      respectively, for which high quality sequenced genomes are available.

PMID- 17005333
TI  - Homologous recombination and the pattern of nucleotide substitution in Ehrlichia
      ruminantium.
AB  - Patterns of nucleotide substitution at orthologous loci were examined between
      three genomes of Ehrlichia ruminantium, the causative agent of heartwater disease
      of ruminants. The most recent common ancestor of two genomes (Erwe and Erwo)
      belonging to the Welgevonden strain was estimated to have occurred 26,500-57,000
      years ago, while the most recent common ancestor of these two genomes and the
      Erga genome (Gardel strain) was estimated to have occurred 2.1-4.7 million years
      ago. The search for genes showing extremely high values of the number of
      synonymous substitutions per site was used to identify genes involved in past
      homologous recombination. The most striking case involved the map1 gene, encoding
      major antigenic protein-1; evidence for homologous recombination is consistent
      with previous phylogenetic analysis of map1 alleles. At this and certain other
      loci, homologous recombination may have contributed to the evolution of host
      pathogen interactions. In addition, comparison of the patterns of synonymous and
      nonsynonymous substitution provided evidence for positive selection favoring a
      high level of amino acid change between the Welgevonden and Gardel strains at a
      locus of unknown function (designated Erum4340 in the Erwo genome).

PMID- 17005334
TI  - Genomic heterogeneity in the density of noncoding single-nucleotide and
      microsatellite polymorphisms in Plasmodium falciparum.
AB  - The density and distribution of single-nucleotide polymorphisms (SNPs) across the
      genome has important implications for linkage disequilibrium mapping and
      association studies, and the level of simple-sequence microsatellite
      polymorphisms has important implications for the use of oligonucleotide
      hybridization methods to genotype SNPs. To assess the density of these types of
      polymorphisms in P. falciparum, we sampled introns and noncoding DNA upstream and
      downstream of coding regions among a variety of geographically diverse parasites.
      Across 36,229 base pairs of noncoding sequence representing 41 genetic loci, a
      total of 307 polymorphisms including 248 polymorphic microsatellites and 39 SNPs
      were identified. We found a significant excess of microsatellite polymorphisms
      having a repeat unit length of one or two, compared to those with longer repeat
      lengths, as well as a nonrandom distribution of SNP polymorphisms. Almost half of
      the SNPs localized to only three of the 41 genetic loci sampled. Furthermore, we
      find significant differences in the frequency of polymorphisms across the two
      chromosomes (2 and 3) examined most extensively, with an excess of SNPs and a
      surplus of polymorphic microsatellites on chromosome 3 as compared to chromosome
      2 (P=0.0001). Furthermore, at some individual genetic loci we also find a
      nonrandom distribution of polymorphisms between coding and flanking noncoding
      sequences, where completely monomorphic regions may flank highly polymorphic
      genes. These data, combined with our previous findings of nonrandom distribution
      of SNPs across chromosome 2, suggest that the Plasmodium falciparum genome may be
      a mosaic with regard to genetic diversity, containing chromosomal regions that
      are highly polymorphic interspersed with regions that are much less polymorphic.

PMID- 17005335
TI  - Generation and immunogenicity of a recombinant pseudorabies virus expressing cap
      protein of porcine circovirus type 2.
AB  - Porcine circovirus type 2 (PCV2) is associated with post-weaning multisystemic
      wasting syndrome (PMWS), which is an important economical disease affecting the
      pig industry worldwide. In order to develop an effective vaccine for PMWS, a
      recombinant pseudorabies virus (PRV) was generated and tested in piglets in this
      study. The PCV2 open reading frame 2 (ORF2) gene was inserted into pIECMV plasmid
      and co-transfected with PRV Tk-/gE-/LacZ+ genome into IBRS-2 cells to generate a
      recombinant Tk-/gE-/ORF2(+) virus. The expression of PCV2 ORF2 gene in the
      recombinant virus was confirmed by Western blotting and indirect
      immunofluorescence assay (IFA). Four-week-old piglets were immunized by the
      recombinant virus, and the immunogenicity of PRV Tk-/gE-/ORF2(+) was tested by
      PRV-enzyme-linked immunosorbent assay (ELISA), PRV neutralizing assay, ORF2-ELISA
      and ORF2 specific lymphocyte proliferation response. PRV Tk-/gE-/ORF2(+) elicited
      significant humoral immune responses to both PRV and PCV2, and the PCV2-specific
      lymphocyte proliferation response could be detected on day 49 of this experiment.
      These findings suggest that the recombinant PRV Tk-/gE-/ORF2(+) may be a
      potential vaccine against both PCV2 and PRV.

PMID- 17005336
TI  - Isolation of Escherichia coli O157:H7 from the gall bladder of inoculated and
      naturally-infected cattle.
AB  - To determine if Escherichia coli O157:H7 is capable of residing in the gall
      bladder of cattle, inoculation studies were conducted with O157:H7 strain 86-24
      in weaned Holstein calves. Strain 86-24 was isolated from the gall bladders of
      five calves 36 days after inoculation. Two other calves contained the inoculation
      strain in the distal colon but the organism was absent in their gall bladders. A
      second trial in which the calves were euthanized 15 days after inoculation found
      strain 86-24 in six of seven inoculated calves but only in colon and/or rumen
      samples. In a third trial that inoculated eight calves with a four-strain
      cocktail of O157:H7 strains, the gall bladders from all eight animals were
      positive 9 days after inoculation. The colon and rumen samples from these calves
      were also positive. E. coli O157:H7 isolates recovered from bile samples and
      subtyped by pulsed field gel electrophoresis found that three of the four
      inoculation strains were present in one or more of the calves. Thus, residence in
      the gall bladder is not restricted to a single strain. Additional evidence of the
      ability to localize in the gall bladder of cattle was provided by testing the
      bile from 150 gall bladders (five collection dates, 30 samples each) obtained at
      an abbatoir and the isolation of E. coli O157:H7 from four samples (2.7%). This
      study establishes that E. coli O157:H7 can reside transiently or permanently at a
      low level in the gall bladder of cattle.

PMID- 17005337
TI  - Characterization of Th1 activation by Bartonella henselae stimulation in BALB/c
      mice: Inhibitory activities of interleukin-10 for the production of interferon
      gamma in spleen cells.
AB  - This study was conducted to analyze cytokine production mechanisms in mice after
      Bartonella henselae stimulation. BALB/c mice were inoculated intraperitoneally
      with 3 x 10(6) colony forming units of B. henselae (Houston-1 strain) twice at 10
      day interval. Spleen cells were harvested from the mice and stimulated with the
      organisms. Following the stimulation, interferon-gamma (IFN-gamma) and
      interleukin-4 (IL-4), IL-10, IL-12 and tumor necrosis factor-alpha (TNF-alpha)
      were measured in the culture supernatants of the spleen cells by ELISA. The
      spleen cells specifically secreted IFN-gamma, but not IL-4, indicating that T
      helper 1 (Th1) cells were activated following B. henselae stimulation. In
      addition, IL-10 and TNF-alpha productions were also detected in the culture
      supernatants of spleen cells. Neutralization of IL-10 in the culture supernatants
      significantly enhanced the production of IFN-gamma from the spleen cells
      stimulated with B. henselae. These results indicate that B. henselae
      predominantly stimulated Th1 cells and resulted in secreting IFN-gamma, however
      the production was partially inhibited by IL-10, which was produced
      simultaneously.

PMID- 17005338
TI  - Amplification and application of the HMG box of bovine SRY gene for sex
      determination.
AB  - A fast and reliable method for bovine sexing has been developed through
      amplification of the bovine high motility group (HMG) box of the sex-determining
      region of the Y chromosome gene (SRY). Oligonucleotide primers were designed
      according to the conserved bovine SRY HMG box sequence motif. In agarose gel
      electrophoresis, a normal bull showed 1 SRY band, and a normal cow showed no SRY
      band. After optimization, the PCR procedure for sex determination was applied to
      14 embryo biopsies. The biopsied embryos were transferred into 14 recipient cows
      on the same day (day 7 of the estrus cycle) that the embryos were collected and
      sex of the calf was confirmed after parturition. Nine calves were born and
      anatomical sex corresponded to those sex determined by PCR in all cases (100%
      accuracy). Thus, this study showed for the first time that the present method can
      be applied in bovine breeding programs to facilitate manipulation of the sex
      ratio of offspring and also allows a quick diagnosis for the XY-bovine offspring
      by amplification of the HMG box of the bovine SRY gene.

PMID- 17005339
TI  - Granule breakage during drying processes.
AB  - The drying of wet granules often involves an unwanted and uncontrolled size
      reduction. Current FDA PAT guidance stresses importance of process control and
      understanding. The aim of this study is to determine and understand the breakage
      phenomena during drying processes in order to control these processes. High shear
      granulated lactose granules with water as binding liquid were dried during
      variable periods. Subsequently the (partially) dried granules were exposed to
      agitation by the impeller and chopper in the granulator. Granule characterization
      revealed that the change in granule size of (partially) dried granules is
      dependent on water content and follows a three phase system characterized by a
      growth, plateau and breakage phase. The derived yield stress of the granules is a
      function of velocity. From this it is concluded that in the plateau phase above
      minimum water content, stress behavior of granules can be described with Rumpfs'
      dynamic granule strength, whereas below minimum water content (breakage phase)
      granule strength is determined by the solid bridges. The extent and velocity of
      stress and water content of the granules during the process determine the size
      reduction phenomena.

PMID- 17005340
TI  - Detection and characterization of protein aggregates by fluorescence microscopy.
AB  - Aggregation may compromise the stability as well as the biological activity of
      protein drugs. Detection of protein aggregates is needed in the process of
      protein characterization and during optimization of pharmaceutical formulations.
      This paper describes a technique, which consists of analysing protein aggregates
      by fluorescence microscopy after staining with the hydrophobic probe Nile Red.
      Dilution, filtration or other modifications of the sample are not needed.
      Assessment of aggregation was possible in highly concentrated protein samples
      (193 mg/ml). Fluorescence microscopy observations allowed the detection and
      characterization of protein aggregates not easily detected by spectroscopic
      techniques. Nile Red was shown to be very sensitive for the detection and
      analysis of immunoglobulin aggregates. Nile Red, Congo red and Thioflavine T
      stainings were compared. Nile Red and Thioflavine T fluorescence were
      colocalized. The diameter of immunoglobulin aggregates was determined, and the
      number of aggregates was correlated with 90 degrees light scattering
      measurements. Studies of human calcitonin aggregates brought to light new aspects
      of the human calcitonin aggregation mechanisms. Thus, Nile Red staining not only
      allows detection of very low levels of protein aggregates, but also contributes
      to a better understanding of the complex mechanisms governing protein
      aggregation.

PMID- 17005341
TI  - Fetuin mediates hepatic uptake of negatively charged nanoparticles via scavenger
      receptor.
AB  - We tried to evaluate the possible involvement of fetuin in the scavenger
      receptors (SRs)-mediated hepatic uptake of polystyrene nanospheres with the size
      of 50 nm (NS-50), which has surface negative charge (zeta potential=-21.8+/-2.3
      mV). The liver perfusion studies in rats revealed that the hepatic uptake of NS
      50 pre-coated with fetuin (NS-50-fetuin) was significantly inhibited by poly
      inosinic acid (poly I), a typical inhibitor of SRs, whereas that of plain NS-50
      or NS-50 pre-coated with BSA (NS-50-BSA) was not. The uptake of NS-50-fetuin by
      cultured Kupffer cells was also significantly inhibited by poly I, and anti-class
      A scavenger receptors (SR-A) antibody, suggesting that fetuin on NS-50 mediated
      the recognition and internalization of NS-50 by Kupffer cells and at least SR-A
      would be responsible for the uptake. Taken that Western blot analysis confirmed
      that fetuin certainly adsorbed on the surface of NS-50 after the incubation of NS
      50 with serum, the results obtained in the present study indicate that fetuin
      would be one of the serum proteins that were substantially involved in the
      hepatic uptake of NS-50 via SRs.

PMID- 17005342
TI  - Prestin gene expression in the rat cochlea following intense noise exposure.
AB  - Noise-induced permanent loss of cochlear amplification was observed previously
      with the majority of outer hair cells (OHCs) still surviving in the cochlea and
      even with a normal OHC receptor potential, indicated by CM (cochlear
      microphonics) recording [Chen, G.D., Fechter, L.D., 2003. The relationship
      between noise-induced hearing loss and hair cell loss in rats. Hear. Res. 177(1
      2), 81-90; Chen, G.D., Liu, Y., 2005. Mechanisms of noise-induced hearing loss
      potentiation by hypoxia. Hear. Res. 200, 1-9]. This study focused on effects of
      an intense noise exposure (10-20 kHz at a level of 110 dB SPL for 4 h) on the OHC
      motor protein (prestin) and structural proteins in the OHC membrane skeleton. The
      noise exposure significantly disrupted CM and CAP (cochlear compound action
      potential). The injured CM recovered after 1-week resting period. The impaired
      CAP at frequencies lower than the noise band also recovered. However, the CAP
      recovery at frequencies of the noise band stopped at a linear line one week after
      the noise exposure, indicating a permanent loss of cochlear amplification. Gene
      expression of prestin, beta-spectrin, and beta-actin was significantly up
      regulated after the noise exposure. The elevated gene expression peaked at the
      3rd post-exposure day and returned to baseline 4 weeks after the noise exposure.
      The up-regulated gene expression may be in response to injury of the proteins,
      which may be responsible for the loss of cochlear amplification.

PMID- 17005343
TI  - Synaptic alterations at inner hair cells precede spiral ganglion cell loss in
      aging C57BL/6J mice.
AB  - Hearing deficits have often been associated with loss of or damage to receptor
      hair cells and/or degeneration of spiral ganglion cells. There are, however, some
      physiological abnormalities that are not reliably attributed to loss of these
      cells. The afferent synapse between radial fibers of spiral ganglion neurons and
      inner hair cells (IHCs) emerges as another site that could be involved in
      transmission abnormalities. We tested the hypothesis that the structure of these
      afferent terminals would differ between young animals and older animals with
      significant hearing loss. Afferent endings and their synapses were examined by
      transmission electron microscopy at approximately 45% distance from the basal end
      of the cochlea in 2-3 month-old and 8-12 month-old C57BL/6J mice. The number of
      terminals in older animals was reduced by half compared to younger animals. In
      contrast, there was no difference in the density of SGCs between the age groups.
      Older animals featured enlarged terminals and mitochondria and enlarged
      postsynaptic densities and presynaptic bodies. These morphological changes may be
      a combination of pathologic, adaptive and compensatory responses to sensory
      dysfunction. Improved knowledge of these processes is necessary to understand the
      role of afferent connectivity in dysfunction of the aging cochlea.

PMID- 17005345
TI  - The analgesic effect of Carum copticum extract and morphine on phasic pain in
      mice.
AB  - Pain is a universal complaint, which needs further investigations for new pain
      relieving agents. Carum copticum (L.) Sprague ex Turrill is a plant in
      Umbelliferae family, which is mentioned to have some therapeutic effects on
      headache and joint pains in Iranian traditional literature, but there are not
      enough scientific reports to prove its effects on pain. So, we conducted to
      design an experimental clinical trial study to assess and compare the analgesic
      effect of ethanolic extract of Carum copticum fruit with morphine by using a tail
      flick analgesiometer device. Our results indicate that the test drug produced
      significant increase in tail-flick latency (TFL) during 2h post-drug
      administration (p<0.05). The peak of the effect was observed at 45min after drug
      injection, which was comparable to that of 1mg/kg morphine (i.p.). Positive
      results in this type of analgesiometric test indicate that the antinociceptive
      action may be of the opoid type. The present study supports the claims of Iranian
      traditional medicine showing that Carum copticum extract possesses a clear-cut
      analgesic effect. However, further investigations are required to evaluate the
      efficacy and safety of this herbal medication in man.

PMID- 17005344
TI  - JNK signaling in neomycin-induced vestibular hair cell death.
AB  - Mechanosensory hair cells are susceptible to apoptotic death in response to
      exposure to ototoxic drugs, including aminoglycoside antibiotics. The c-Jun n
      terminal kinase (JNK) is a stress-activated protein kinase that can promote
      apoptotic cell death in a variety of systems. Inhibition of the JNK signaling
      pathway can prevent aminoglycoside-induced death of cochlear and vestibular
      sensory hair cells. We used an in vitro preparation of utricles from adult mice
      to examine the role of JNK activation in aminoglycoside-induced hair cell death.
      CEP-11004 was used as an indirect inhibitor of JNK signaling.
      Immunohistochemistry showed that both JNK and its downstream target c-Jun are
      phosphorylated in hair cells of utricles exposed to neomycin. CEP-11004 inhibited
      neomycin-induced phosphorylation of both JNK and c-Jun. CEP-11004 inhibited hair
      cell death in utricles exposed to moderate doses of neomycin. However, the
      results were not uniform across the dose-response function; CEP-11004 did not
      inhibit hair cell death in utricles exposed to high-dose neomycin. The CEP-11004
      induced protective effect was not due to inhibition of PKC or p38, since neither
      Chelerythrine nor SB203580 could mimic the protective effect of CEP-11004. In
      addition, inhibition of JNK inhibited the activation of caspase-9 in hair cells.
      These results indicate that JNK plays an important role in neomycin-induced
      vestibular hair cell death and caspase-9 activation.

PMID- 17005346
TI  - Epilepsy surgery in a patient with Lennox-Gastaut syndrome and cortical
      dysplasia.
AB  - Lennox-Gastaut syndrome (LGS) is classified as a generalized epilepsy, and is
      often intractable to antiepileptic drugs. Although corpus callosotomy may
      sometimes control drop attacks, curative epilepsy surgery is rarely possible in
      LGS. We report, here, a patient with LGS and focal cortical dysplasia, who became
      seizure-free after epilepsy surgery. The patient was a 24-month-old boy without
      perinatal insult in whom seizures began 7 days after birth and who experienced
      development delay. Brain magnetic resonance imaging (MRI) showed focal cortical
      lesion with calcification in the right frontal area. At age 13 months, his
      seizure type changed from tonic seizures to head drops (atonic types) and
      atypical absence seizures. His interictal electroencephalogram (EEG) showed
      generalized slow spike and wave discharges, and he was diagnosed with LGS. His
      seizures were intractable to medical treatment, and a ketogenic diet was not
      effective. He was evaluated prior to surgery by long-term video-EEG monitoring,
      which detected many seizures consisted of a sudden onset of falling attacks
      (atonic type) intermittently followed by atypical absence seizures with diffuse
      slow wave bursts followed by slow spike and wave discharges in ictal EEG, brain
      positron emission tomography (PET) and MRI. A right frontal lesionectomy with
      intra-operative electrocorticography (EcoG) was performed. From the time of
      lesionectomy to the present, the patient has been seizure free and has been
      developing normally. Our results suggest that focal resective surgery should be
      considered in patients with LGS and focal epileptic lesions.

PMID- 17005347
TI  - Epilepsy development in infancy with epileptic discharges.
AB  - As a part of the study to prevent West syndrome (WS) by early treatment, we
      assessed what kind of epilepsy developed in infants who showed epileptic
      discharges in early infancy. EEG examinations were performed on 116 infants born
      from 1997 to September 2004, both before and after 3 months of corrected age
      (CA). We divided 45 infants who showed epileptic discharges in early infancy into
      two groups according to the existence of periventricular leukomalacia (PVL) and
      retrospectively performed the course observation at the survey point on April 1
      in 2005. Out of 45 infants showing epileptic discharges in early infancy, 26
      developed WS. Compared with infants without PVL, infants with PVL were more
      likely to develop WS than infants without PVL. Furthermore, infants with PVL were
      more likely to develop WS than other types of epilepsy. Namely, 11 out of 17
      infants with PVL developed WS at the survey point. All infants with WS showed
      initial epileptic discharges before 5 months of corrected age (CA), and most of
      them (except for five) had initial epileptic discharges before 3 months of CA.
      There were two infants who once developed hypsarrhythmia on EEG; however, after
      starting VPA therapy, they did not develop WS with the improvement of EEG
      findings, and one was presented here in detail. We proposed that preterm infants
      with PVL who showed epileptic discharges before 3 months of CA should be treated
      by antiepileptic drugs to prevent the onset of WS syndrome.

PMID- 17005348
TI  - Spontaneous resolution of intractable epileptic seizures following HHV-7
      infection.
AB  - PURPOSE: We report a three-year-old female with intractable epilepsy post West
      syndrome whose seizures disappeared following an acute viral infection, without
      changes in anti-epileptic therapy. METHODS: The female infant was born at term to
      a healthy mother after an uneventful pregnancy and delivery. At the age of five
      months, she developed intractable brief tonic spasms which had a series of
      infantile spasms, and an electroencephalogram indicated hypsarrhythmia. She was
      diagnosed with West syndrome. The seizures were uncontrollable with conventional
      therapy, including ACTH, vigabatrin, sodium valproate, clonazepam, zonisamide,
      and ketogenic diet. Daily multiple generalized tonic seizures and brief tonic
      spasms were observed before an episode of viral infection. RESULTS: At the age of
      three years, the intractable seizures disappeared after a febrile rash illness
      due to human herpesvirus 7 (HHV-7) infection, without changes in anti-epileptic
      drugs. CONCLUSIONS: The disappearance of intractable epileptic seizures following
      acute viral infections might be related to the inflammatory or immunologic
      processes associated with viral infections. This is the first documented case of
      spontaneous remission of intractable epileptic seizures following HHV-7
      infection.

PMID- 17005349
TI  - MR contrast agents, the old and the new.
AB  - Magnetic resonance (MR) contrast agents are increasingly being used to help
      detect and characterize various neoplastic, inflammatory and functional
      abnormalities. The extracellular, non-specific contrast agents gadolinium
      chelates are by far the most widely used. Over the past few years a number of MR
      organ specific contrast agents have been introduced. MRI contrast agents are
      generally safe and well tolerated. The present review summarizes the properties,
      main characteristics and imaging applications of commercially available compounds
      as well as safety of these agents in normal and high-risk patients.

PMID- 17005350
TI  - [Subarachnoidal haemorrhage and myocardial failure: interest of cardiac and
      cerebral monitoring].
AB  - Spontaneous subarachnoidal haemorrhage can be associated with neurogenic
      pulmonary oedema and cardiogenic shock. The presentation is an ischemic
      myocardial dysfunction associated with normal coronary arteries. Hypoxaemia
      associated with arterial hypotension on patients with brain injury can worsen
      neurological outcome. The administration of norepinephrine associated with fluid
      expansion could be deleterious on cardiac function. We report the case of a
      patient with acute pulmonary oedema associated with post-aneurysmal subarachnoid
      haemorrhage managed with transoesophageal Doppler monitoring.

PMID- 17005351
TI  - [Infection risk factors after cardiac surgery. Personal experience].

PMID- 17005352
TI  - [Benchmark of a high-frequency jet ventilator, the Mistral].
AB  - OBJECTIVE: To test a high-frequency jet ventilator, the Mistral (Acutronic
      Laboratory) on a lung model. METHODS: The jet ventilator Mistral was tested with
      two connectors (7 and 20 ml) and four catheters. Pressure and flow measurements
      were performed by varying the driving pressure (1 to 3 bars), the I/T ratio
      (0.25, 0.35, 0.45) and the frequency (1 to 5 Hz). Recorded data were: the volume
      delivered by the ventilator, the pressure measured in the connecting line between
      the ventilator and the injector and the difference between the end expiratory
      pressure measured by the ventilator through the injector and the tracheal
      pressure. RESULTS: An increase in driving pressure induced a proportional
      increase in minute volume whatever the injection catheter used. After
      insufflation, when a Seldicath catheter was used, the pressure decrease was the
      slowest and the time constant the longest. Increase in frequency or I/T ratio,
      particularly beyond 0.35, was associated with an increase of the end expiratory
      pressure measured by the respirator. The gradient of pressure measured by the
      respirator and by an external sensor was lower with the 7 ml connector whatever
      the catheter used, and was larger with the Seldicath catheter. CONCLUSION: The
      use of a low volume connector should be preferred, because it allows the
      measurement of the end expiratory pressure for a larger range of driving
      pressure, expiratory time and catheters. The performances of the Seldicath
      catheter are below those of the other catheters studied.

PMID- 17005353
TI  - [Unusual haemostasis disorder in a seriously burned patient].
AB  - We report the case of a woman severely burned during a gas explosion with an
      unusual disorder of haemostasis. The prothrombin time was very elevated,
      essentially by a drop in factor II. This abnormality persisted for a long time
      after the correction of the dilutional and consumption coagulopathy which
      followed immediately the burn. Blood analysis found fluindione and benzodiazepine
      derivatives. Such a disorder during a potentially suicidal burn must evoke a
      toxic aetiology.

PMID- 17005354
TI  - [Introduction of the intubating Laryngeal Mask Airway in a prehospital emergency
      medical unit].
AB  - OBJECTIVES: Assessment of the intubating Laryngeal Mask Airway(trade mark) in a
      prehospital emergency mobile unit (PEMU). STUDY DESIGN: Observational study.
      METHODS: All the emergency physicians and nurses of the PEMU were trained with
      the intubating laryngeal mask (ILMA) handling on manikin and a learning curve was
      carried out. One year after the initial formation, a reassessment of the
      operators was performed. Following the initial formation, all the vehicles of the
      PEMU were equipped with ILMA and during 15 months all cases of ILMA use were
      recorded. The success rate and the difficulties met were analysed. RESULTS:
      Initial formation on manikin showed that at least 8 handling of the device were
      mandatory to achieve a 100% success rate. A significant reduction of tracheal
      tube insertion delay was observed up to the eight manipulations. One year after
      the initial formation, a significant loss of performance was observed. Over the
      clinical study period 20 ILMA were used with adequate ventilation through the
      mask in all cases and a possible intubation in 80% of the patients. CONCLUSION:
      The ILMA is a potential useful device in the prehospital setting. Initial
      formation and maintenance of the skill acquired with this technique are
      essential.

PMID- 17005355
TI  - [Misplacement of a central femoral catheter in the urinary conduit of a renal
      transplant].
AB  - Femoral vein catheterization is often carried out during resuscitation and in
      critical care units. Thrombosis and infections are the most current reported
      complications. Catheter malpositions have been reported. We described the
      inadvertent cannulation of the urinary tractus in a patient with a right iliac
      renal transplant.

PMID- 17005356
TI  - [Misleading diagnosis of a migratory epigastric pain in mobile emergency units:
      spontaneous rupture of the oesophagus].
AB  - The local mobile emergency unit took charge of a patient who suffered from a
      sudden migratory epigastric pain in the back. The clinical picture led to an
      initial diagnosis of an aorta dissection. Admitted to Grenoble UH's emergency
      unit, the radiological examination ruled out a cardiovascular pathology.
      Emergency surgery, performed only a few hours after the symptoms began, allowed
      to correctly diagnose a spontaneous rupture of the oesophagus. Fast and
      specialised medical treatment avoided the risk of an unfavourable development of
      the Boerhaave's syndrome. It is essential that mobile emergency units personnel
      are made aware of this rare pathology, even though it remains particularly
      difficult to diagnose due to its rather non-specific symptoms.

PMID- 17005357
TI  - [HELLP syndrome and ruptured subcapsular hepatic haematoma. Case report and
      therapeutic options].
AB  - We report a case of spontaneous hepatic rupture secondary to HELLP syndrome. A
      favourable evolution was observed after massive transfusion and surgical
      management limited to hepatic packing. Subcapsular hepatic haematoma is a rare
      complication of preeclampsia occurring mainly in the context of HELLP syndrome. A
      high maternal and foetal mortality is observed. Different therapeutic options are
      presented including medical, surgical and radiological interventions. A unique
      strategy cannot be defined. Multidisciplinary approach seems mandatory. Surgery
      should remain as less aggressive as possible.

PMID- 17005358
TI  - [Metformin-associated lactic acidosis].
AB  - OBJECTIVE: The aims of this review are to precise the pathophysiological
      mechanisms leading to biguanide-associated lactic acidosis, to give elements of
      diagnosis, and to underline the precautionary conditions for prescribing these
      drugs by an improvement in physicians and patient's education. DATA SOURCES: A
      PubMed database research in English and French language reports published until
      December 2005. The keywords were: lactic acidosis, metformin, biguanide, diabetes
      mellitus. DATA EXTRACTION: Data in selected articles were reviewed, clinical and
      basic science research relevant informations were extracted. DATA SYNTHESIS:
      Metformin, which is an oral antidiabetic agent, is the only one biguanide
      available in France. It acts by enhancing the sensitivity to insulin by a
      decrease in the hepatic glucose production and an increase in its peripheral use.
      In term of glycemic control, it has the same efficiency than the other
      hypoglycemic agents. It represents the treatment of choice for overweight type 2
      diabetic patients because of its beneficial effects on the weight loss and on the
      cardiovascular complications. The incidence of metformin-associated lactic
      acidosis is very low when contra-indications and appropriate rules for
      prescribing this drug are respected. The relationship between metformin and
      lactic acidosis remains largely controversial. In practical, we can distinguish
      three situations which have different prognosis. In the first case, metformin
      seems to be responsible for lactic acidosis because of self-poisoning or
      accidental overdose, and prognosis is good. In the second case, the association
      between metformin and lactic acidosis is coincidental rather than causal, and may
      be induced by an underlying organ failure. In the last case there is a cause of
      lactic acidosis which is worsened by a precipitating factor leading to metformin
      accumulation. The 2 latter situations are very severe as mortality rate is about
      50%. Symptomatic treatments and renal replacement therapy which allows metformin
      removal are the curative treatment. Prevention is essential. It requires the
      respect of metformin contraindications and a better education of physicians and
      patients for a safe prescription. CONCLUSION: Due to its beneficial effects,
      metformin is the gold standard treatment for overweight type 2 diabetic patients.
      The essential precautionary conditions for prescribing metformin as well as the
      respect of its contra-indications permit largely to prevent lactic acidosis. This
      complication is serious when it is associated with intercurrent illnesses and
      metformin accumulation. The curative treatment is based on renal replacement
      therapy. Prevention only rests on the respect of the contra-indications.
      Education of physicians and patients concerning the rules of prescription remains
      essential.

PMID- 17005359
TI  - [Impact of the guidelines on clinical practice of artificial nutrition in
      intensive care unit after cardiovascular and thoracic surgery].
AB  - OBJECTIVE: To analyze the impact of an artificial nutrition program in post
      anaesthesia intensive care unit. STUDY DESIGN: Observational study. PATIENTS AND
      METHODS: Patients with length of stay greater than 8 days after cardiovascular
      and thoracic surgery: Group 1: 34 patients (4-month period in 2000); group 2: 15
      patients (2-month period in 2001); group 3: 40 patients (4-month period in 2003).
      Between these 3 periods, informations of physicians and written protocol in order
      to improve their nutritional knowledge. After analysis of variance (P<0.05).
      Newman-Keuls tests to compare themselves each groups. RESULTS: Anthropometric,
      demographic and clinical parameters were similar in the 3 groups. Energic intakes
      were less than 80% of basal energetic expenditures in 33%, 33 and 22% of patient,
      respectively (NS). Caloric and nitrogen intakes were less than recommended,
      respectively 19+/-6 (mean+/-SD), 21+/-7 and 21+/-8 kcal/kg/24 h and 102+/-32,
      111+/-31 and 92+/-40 mg/kg/24 h (NS). However enteral nutrition was administered
      in 49, 40 and 100% of patients respectively (P<0.001). The glucid/lipid ratio
      improved from 0.47 in group 1 up to 0.68 in group 3 (P<0.0001). Vitamins,
      oligoelements and clinical and biological monitoring of artificial nutrition
      improved (P<0.001). CONCLUSION: A clinical audit demonstrated an improvement in
      artificial nutrition parameters but no significant change in others.

PMID- 17005360
TI  - [Intrathecal catheter after wet tap in labour: headache prevention?].

PMID- 17005361
TI  - [Brain death management and organ procurement: an ethical activity for
      intensivists].

PMID- 17005362
TI  - [Prevention of myoclonus after etomidate using a priming dose].
AB  - OBJECTIVE: To investigate the influence of pretreatment with a low dose of
      etomidate (priming dose) on the incidence of etomidate-induced myoclonus. STUDY
      DESIGN: Prospective randomized double-blind study. METHODS: Forty six patients
      ASA physical status I - II, scheduled for abdominal elective surgery, were
      allocated randomly to receive either pre-treatment 0.03 mg/kg of etomidate
      (priming group) or placebo (control group). Sixty-seconds after the pre-treatment
      was injected, anesthesia was induced with etomidate 0.3 mg/kg and 60 seconds
      later induction was completed with fentanyl (3 microg/kg) and vecuronium (0.1
      mg/kg). The occurrence and intensity of myoclonus were graded clinically by a
      blinded observer as: 0=no myoclonus, 1=mild myoclonus, 2=moderate myoclonus and
      3=severe myoclonus. STATISTICAL ANALYSIS: Fisher test exact for qualitative
      variable and Student t-test for quantitative variables. RESULTS: Demographic data
      and the average dose of etomidate used during the induction were similar in the 2
      groups (0.29+/-0.032 mg/kg in the priming group and 0.30+/-0.029 mg/kg in the
      control group). Twenty patients (87%) in the control group experienced myoclonic
      movements whereas only 6 patients (26%) in the control group had such movements
      (P<0,001). CONCLUSION: Pretreatment with etomidate (0.03 mg/kg), given 60 seconds
      before induction of anesthesia, is effective at reducing etomidate-induced
      myoclonus, without related side-effect.

PMID- 17005363
TI  - [Donation after cardiac death: perspective of recruiting by French EMS system].

PMID- 17005364
TI  - [Is there a place for activated protein C (Xigris) in the treatment of severe
      imported malaria in the adult?].

PMID- 17005365
TI  - Pain hypersensitivity in rats with experimental autoimmune neuritis, an animal
      model of human inflammatory demyelinating neuropathy.
AB  - Experimental autoimmune neuritis (EAN) is a T cell mediated autoimmune disease of
      the peripheral nervous system that serves as an animal model of the acute
      inflammatory demyelinating polyradiculoneuropathy in Guillain-Barre syndrome
      (GBS). Although pain is a common symptom of GBS occurring in 55-85% of cases, it
      is often overlooked and the underlying mechanisms are poorly understood. Here we
      examined whether animals with EAN exhibit signs of neuropathic pain including
      hyperalgesia and allodynia, and assessed their peripheral nerve autoimmune
      inflammation. We immunized Lewis rats with peripheral myelin P2 peptide (amino
      acids 57-81) emulsified with complete Freund's adjuvant, or with adjuvant only as
      control. P2-immunized rats developed mild to modest monophasic EAN with disease
      onset at day 8, peak at days 15-17, and full recovery by day 28 following
      immunization. Rats with EAN showed a significant decrease in withdrawal latency
      to thermal stimuli and withdrawal threshold to mechanical stimuli, in both
      hindpaws and forepaws, during the course of the disease. We observed a
      significant infiltration of T cells bearing alphabeta receptors, and a
      significant increase in antigen-presenting cells expressing MHC class II as well
      as macrophages, in EAN-affected rats. Our results demonstrate that animals with
      active EAN develop significant thermal hyperalgesia and mechanical allodynia,
      accompanied by pronounced autoimmune inflammation in peripheral nerves. These
      findings suggest that EAN is a useful model for the pain seen in many GBS
      patients, and may facilitate study of neuroimmune mechanisms underlying pain in
      autoimmune neuropathies.

PMID- 17005366
TI  - Neonatal administration of diethylstilbestrol has adverse effects on somatic
      cells rather than germ cells.
AB  - Neonatal administration of diethylstilbestrol (DES) to rodents has adverse
      effects on spermatogenesis. However, not many studies have been conducted to
      determine which type of cell - germ or somatic - is the major target of DES. In
      order to clarify this, we tried reciprocal germ cell transplantation-
      transplantation of germ cells from DES-treated mice into intact mice and germ
      cells from normal mice into DES-treated mice. The donor germ cells were tagged
      with the green fluorescent protein (GFP) gene in order to distinguish the
      exogenous germ cells from the endogenous cells. Moreover, to obtain a large
      number of spermatogonia from the testes of adult mice, we performed fractionation
      by centrifugation with Percoll. Consequently, we found that the germ cells
      collected from DES-treated mice have differentiated into normal sperms in normal
      seminiferous tubules. However, in the case of the transplantation of normal germ
      cells into the seminiferous tubules of DES-treated mice, defective
      spermatogenesis was observed. In conclusion, DES has adverse effects on the
      somatic cells that are involved in spermatogenesis rather than the germ cells.

PMID- 17005367
TI  - Morphological changes in the testis induced by diethylcarbamazine.
AB  - Diethylcarbamazine (DEC) had been proved to be highly effective against lymphatic
      filariasis, however its effect on vertebrate cells remains uncertain. After 12
      days treatment with DEC, most of the Leydig cells were hypertrophied with several
      lipid droplets, and others had no nucleus and presented characteristic steatosis
      features. Vacuolization of Sertoli cells was also noted. Ultrastructural analyses
      of DEC-treated testes revealed spermatogonies with morphological characteristics
      of apoptosis, as shrinkage of cytoplasm and increased chromosomal density. In
      addition, Leydig cells showed numerous lipid droplets scattered throughout the
      cytoplasm, multivesicular bodies and giant whorl-like smooth endoplasmic
      reticulum. Several spermatids presented vacuolated mitochondriae, which were
      disorganized in relation to the microtubular axis of the flagellae. These results
      indicate that DEC probably affects the microtubular function, however the present
      data does not exclude the possibility that DEC also can act directly on enzymatic
      hormonal pathways.

PMID- 17005368
TI  - Prenatal cadmium and ethanol increase amphetamine-evoked dopamine release in rat
      striatum.
AB  - To explore interactive deleterious effects of the teratogens ethanol and cadmium,
      pregnant rats were given cadmium (CdCl(2), 50 ppm) and/or ethanol (10%), or tap
      water (controls) in the drinking water for the entire 21 days of pregnancy. At 3
      months after birth, in vivo microdialysis was used to determine that there was a
      4000% evoked release of DA by AMPH (AMPH, 4.0 mg/kg i.p.) in the striatum of rats
      exposed prenatally to both ethanol and cadmium, vs. a 2000% evoked release by
      AMPH in rats exposed prenatally to only ethanol or cadmium or tap water.
      Haloperidol (HAL)-evoked DA release was suppressed in groups exposed prenatally
      to ethanol, while HAL-evoked DOPAC and HVA release was greatest after co-exposure
      to prenatal cadmium and ethanol. These in vivo microdialysis results indicate
      that ontogenetic co-exposure to cadmium, and ethanol produces a long-lived
      suppressive effect on HAL-evoked DA release and a long-lived enhancing effect on
      AMPH-evoked DA release in rat striatum. These findings clearly demonstrate that
      there is marked alteration in dopaminergic regulation after ontogenetic cadmium
      and ethanol co-exposure, which in this regard resembles the reaction of the
      striatonigral pathway on AMPH-evoked DA release in rats with behavioral
      sensitization.

PMID- 17005370
TI  - Topological relationships between brain and social networks.
AB  - Brains are complex networks. Previously, we revealed that specific connected
      structures are either significantly abundant or rare in cortical networks.
      However, it remains unknown whether systems from other disciplines have similar
      architectures to brains. By applying network-theoretical methods, here we show
      topological similarities between brain and social networks. We found that the
      statistical relevance of specific tied structures differs between social
      "friendship" and "disliking" networks, suggesting relation-type-specific topology
      of social networks. Surprisingly, overrepresented connected structures in brain
      networks are more similar to those in the friendship networks than to those in
      other networks. We found that balanced and imbalanced reciprocal connections
      between nodes are significantly abundant and rare, respectively, whereas these
      results are unpredictable by simply counting mutual connections. We interpret
      these results as evidence of positive selection of balanced mutuality between
      nodes. These results also imply the existence of underlying common principles
      behind the organization of brain and social networks.

PMID- 17005369
TI  - Diphenyl diselenide changes behavior in female pups.
AB  - Diphenyl diselenide, (PhSe)(2), is an organoselenium compound that affects a
      number of neuronal processes. The effect of maternal subcutaneous (s.c.)
      injection of 25 mg/kg (PhSe)(2) once daily during early postnatal development
      (from PND 1 to 21) was evaluated in offspring of Wistar rats. The physical and
      neural reflexes were recorded at pre-weaning period. The behavioral changes in
      the elevated plus-maze (EPM), open-field and rotarod tasks were performed in 28
      day-old pups. Selenium brain status was significantly increased ( approximately
      41%) in rat pups. Statistically significant decreases in body weight were
      observed during lactation period in male and female pups exposed to 25 mg/kg
      (PhSe)(2). There were no dose-related changes on landmarks indicative of physical
      and reflexologic parameters of development in rats. (PhSe)(2) induced a
      disinhibitory effect in EPM behavior according to gender. Specifically, exposure
      to (PhSe)(2) increased entries and duration in the open arms of the EPM in
      females but not in males. Locomotor activity and rearing increased by (PhSe)(2)
      exposure in both male and female offspring in the open field. Both groups were
      similar in response to motor coordination in the rotarod. We concluded that
      maternal (PhSe)(2) exposure during lactation increased selenium levels in the pup
      brain and caused changes on developmental and behavioral parameters of Wistar rat
      offspring.

PMID- 17005371
TI  - Polyglutamine-expanded ataxin-7 decreases nuclear translocation of NF-kappaB p65
      and impairs NF-kappaB activity by inhibiting proteasome activity of cerebellar
      neurons.
AB  - Our recent study indicated that polyglutamine-expanded ataxin-7-Q75 induced
      apoptotic death of cultured cerebellar neurons by downregulating Bcl-x(L)
      expression and activating mitochondrial apoptotic cascade. Mutant polyglutamine
      expanded proteins are believed to impair the proteolytic function of ubiquitin
      proteasome system by sequestering components of proteasomes. Proteasome
      degradation of IkappaBalpha permits nuclear translocation of NF-kappaB and is
      required for continuous NF-kappaB activity, which supports the survival of
      cultured cerebellar neurons by inducing Bcl-x(L) expression. Thus, we tested the
      hypothesis that mutant ataxin-7-Q75 causes proteasome dysfunction and impairs NF
      kappaB activity, leading to reduced Bcl-x(L) expression, caspase activation and
      cerebellar neuronal death. EMSA assays indicate that DNA-binding activity of NF
      kappaB was significantly decreased in cerebellar neurons expressing ataxin-7-Q75.
      Similar to mutant ataxin-7-Q75, NF-kappaB inhibitor APEQ induced cerebellar
      neuronal death by decreasing Bcl-x(L) expression and activating caspase-9. Mutant
      ataxin-7-Q75 inhibited the proteolytic activity of proteasomes in cerebellar
      neurons. Proteasome inhibitor MG132 also caused cerebellar neuronal death by
      decreasing Bcl-x(L) expression and activating caspase-9. Both ataxin-7-Q75 and
      MG132 caused the cytosolic accumulation of IkappaBalpha in cerebellar neurons.
      Mutant ataxin-7-Q75 or MG132 increased the cytosolic level of NF-kappaB p65 and
      decreased the nuclear NF-kappaB p65 level. Our study provides the evidence that
      polyglutamine-expanded ataxin-7-Q75 decreases nuclear translocation of NF-kappaB
      p65 and impairs NF-kappaB activity by inhibiting proteasome activity of
      cerebellar neurons.

PMID- 17005372
TI  - rh-BMP2-induced ectopic bone for grafting critical size defects: a preliminary
      histological evaluation in rat calvariae.
AB  - The aim of this study was to evaluate histologically the biological usefulness of
      recombinant human BMP2 (rh-BMP2)-induced ectopically-formed bone as graft
      material to repair a bone defect model, compared with autogenous bone and frozen
      allogeneic bone. Forty-five male Wistar rats were used, which were divided into
      three graft groups. Each of the three graft groups was divided into three
      observation period groups (3, 6 and 9 weeks after graft). All rats underwent
      craniotomy to create a bone defect, and then received a bone graft. In the rh
      BMP2-induced ectopic bone graft group, marked bone formation was seen from 3
      weeks after graft. In the autogenous bone graft group, marked bone formation was
      seen from 6 weeks after graft. In the group that received a frozen allogeneic
      bone graft, marked bone formation was seen from 9 weeks after graft. At 3, 6 and
      9 weeks after graft, newly formed bone area was significantly greater in the
      tissue engineered bone (TEB) group than in the auto or frozen allogeneic bone
      (FAB) group. rh-BMP2-induced ectopically-formed bone graft exhibited better
      osteoconductivity than autogenous bone graft and frozen allogeneic bone graft.
      These histological findings indicate that rh-BMP2-induced ectopically-formed bone
      is suitable as bone graft material.

PMID- 17005373
TI  - Disturbances of visual information processing in early states of psychosis and
      experimental delta-9-tetrahydrocannabinol altered states of consciousness.
AB  - Recent data on alterations of the endogenous cannabinoid system in schizophrenia
      have raised the question of its functional role in this disease. The psychoactive
      compound of Cannabis sativa, delta-9-tetrahydrocannabinol (Delta9-THC), has been
      shown to induce psychotic symptoms, but it is unknown to what extend prodromal
      states of psychoses are reflected by these experimental approaches. This study
      compares four groups of subjects: antipsychotic-naive patients suffering from
      acute paranoid schizophrenic or schizophreniform psychosis (SZ), patients in the
      prodromal state (IPS), healthy controls without any pharmacological intervention
      (HC) and a second group of healthy volunteers who were orally administered
      synthetic Delta9-THC (Dronabinol) (HC-THC). Neither SZ and IPS nor HC received
      the experimental drug. All subjects were assessed using the Brief Psychiatric
      Rating Scale (BPRS) and the Binocular Depth Inversion Illusion Test (BDII). The
      latter represents a sensitive measure of impaired visual information processing
      that manifests in various experimental and naturally occurring psychotic states.
      BDII values were well comparable in SZ, IPS and HC-THC, and all groups differed
      significantly to HC. The BPRS revealed no significant difference between HC-THC
      and IPS while both were significantly different from SZ and HC, respectively. Our
      results suggest that Delta9-THC-induced altered states of consciousness may serve
      as a useful tool for modeling psychotic disorders, particularly their prodromal
      states. Furthermore, they provide insight into the perceptual and
      psychopathological alterations induced by Delta9-THC, which is essential for the
      understanding of the pro-psychotic effects of herbal cannabis preparations with
      highly enriched Delta9-THC content.

PMID- 17005374
TI  - The relationship between sensorimotor gating and clinical improvement in acutely
      ill schizophrenia patients.
AB  - It has been suggested that sensorimotor gating deficits as indexed by prepulse
      inhibition (PPI) of the acoustic startle reflex represent an endophenotypic
      marker of psychotic conditions such as schizophrenia (SCZ). This hypothesis has
      been questioned as several studies have found that PPI levels change with
      improvement in symptoms and are responsive to medications. We tested PPI in a
      sample of acutely decompensated schizophrenia patients who were re-tested after 2
      weeks of hospital treatment. PPI was assessed at three interstimulus intervals
      (30, 60, and 120 ms) in 23 SCID-diagnosed SCZ patients shortly after admission to
      an inpatient psychiatric hospital. Eight of these patients were initially tested
      in a medication-free state, and all were re-tested approximately 2 weeks later
      after initiation or increase/change of antipsychotic medications. Symptom ratings
      were collected at both sessions. 20 nonpatient comparison subjects (NCS) were
      also tested at a 2-week interval. While SCZ patients showed lower PPI at the
      first session than NCS, after 2 weeks of treatment their PPI increased to levels
      not different than those of NCS. In contrast, the PPI of NCS remained consistent
      over a 2-week period. For the SCZ patients, increase in PPI was correlated with a
      decrease in symptom scores. Our results suggest that PPI can be improved by short
      term treatment, and that improvement in sensorimotor gating is associated with
      treatment-related improvement of symptoms of schizophrenia.

PMID- 17005375
TI  - The Palau Early Psychosis Study: neurocognitive functioning in high-risk
      adolescents.
AB  - OBJECTIVE: The purpose of the present study was to evaluate both the independent
      and joint effects of genetic risk and clinical status on neurocognitive
      functioning in adolescents from a population isolate with an elevated risk for
      schizophrenia and strong familial aggregation of cases. METHOD: The subjects were
      310 non-help seeking, drug-naive adolescents 14-19 years of age from the Republic
      of Palau. The sample comprised 98 Genetically High Risk (GHR) adolescents, 54 of
      whom were symptomatic, and 212 Genetically Low Risk (GLR) adolescents, including
      113 Clinically High Risk (CHR) subjects who were symptomatic and 99 normal
      controls who were non-symptomatic. Neurocognitive testing was conducted after the
      clinical assessment and included Wechsler Memory Scale tests of logical, visual
      and working memory, the perceptual organization and processing speed subtests of
      the WISC-III, CPT-IP measures of sustained attention, and tests of fine and gross
      neuromotor function. RESULTS: GHR adolescents showed impairments in immediate
      logical memory, verbal working memory, CPT-IP performance, and fine motor skills.
      The only two cognitive components influenced by the presence of early psychosis
      symptoms were WISC-III perceptual organization and spatial working memory.
      Neurocognitive deficits did not increase with increasing levels of
      psychopathology. We found no significant interactive effects of genetic risk and
      clinical status on neurocognitive functioning. CONCLUSIONS: Genetic risk and
      clinical status exert independent effects on neurocognitive function in HR
      adolescents, and genetic risk has a broader impact than clinical status. Our
      results suggest that many of the neurocognitive impairments associated with early
      psychosis are genetically mediated and can occur in genetically vulnerable
      individuals regardless of their clinical status. However, visuospatial processing
      appears to be uniquely disrupted by emerging symptomatology.

PMID- 17005376
TI  - Comparison of three computer-administered cognitive tasks as putative
      endophenotypes of schizophrenia.
AB  - It has been repeatedly demonstrated that individuals with schizotypal personality
      features (SPF) exhibit similar endophenotypic traits as persons with
      schizophrenia. Less research has compared the relative sensitivity of different
      endophenotypes in the same sample of individuals with SPF. Fourteen university
      students with SPF (mean age 20.5+/-1.6; 43% male) and 26 controls (mean age
      20.3+/-1.1; 31% male) were defined by the Abbreviated Schizotypal Personality
      Questionnaire (SPQ-B). All participants reported no known biological relative
      with schizophrenia. Participants completed three computer-administered cognitive
      tasks: a 6-min degraded-stimuli A-X Continuous Performance Test (CPT), the
      Wisconsin Card Sort Test (WCST), and a Span of Apprehension (SOA) task (6- and 12
      letter arrays). On the CPT, only omission errors resulted in a statistically
      significant group difference, U=115.5, p=.05, Cohen's d=0.54 (medium effect
      size), with the SPF group (mean errors: 3.43+/-3.28) making more omission errors
      than controls (mean errors: 1.88+/-2.66). Notably, 46% of the controls had no
      omission errors, compared to 14% of the SPF group. The only SPQ-B factor score to
      show a statistically significant linear relationship with CPT omission errors was
      the Cognitive-Perceptual factor (rs=.33, p=.04). Group differences on performance
      indices from the SOA and WCST did not approach statistical significance. Based on
      performance from the community-identified schizotypes, results suggest that
      performance on the CPT may represent a more robust endophenotype of
      schizophrenia, compared to the SOA and WCST.

PMID- 17005377
TI  - Improved and rapid detection of methicillin-resistant Staphylococcus aureus nasal
      carriage using selective broth and multiplex PCR.
AB  - To improve efficiency in detecting nasal methicillin-resistant Staphylococcus
      aureus (MRSA), we evaluated a multiplex PCR using pre-enrichment of the specimen
      in selective broths, and compared it with detection performed by routine tests in
      hospital laboratories. Nasal swab specimens from 311 patients were inoculated
      onto mannitol-salt agar (MSA) at the hospital laboratories and in two Mueller
      Hinton broths with 7% NaCl containing oxacillin at concentrations of 2 and 4
      micro g/ml. Isolates on MSA were identified as MRSA by classical laboratory tests
      (coagulase and oxacillin disk diffusion tests). Oxacillin broth cultures were
      subcultured on blood agar and MRSA isolates were identified by coagulase and
      susceptibility tests, including agar dilution and the oxacillin-screening method
      (gold standard method). Simultaneously, multiplex-PCR was performed from the
      selective broths to detect S. aureus species-specific and mecA gene segments
      (OxMPCR method). Thirty-two S. aureus isolates were recovered: 29 (90.6%) were
      MRSA strains and 3 (9.4%) were oxacillin-susceptible isolates. Twenty-eight
      (96.5%) MRSA isolates were detected by OxMPCR, while 17 (58.6%) were identified
      by routine tests (P=0.002). This new method for detection of MRSA nasal carriers
      showed higher sensitivity and led to faster reporting--i.e., within 24 h--of
      results.

PMID- 17005378
TI  - Bacillus subtilis spores reduce susceptibility to Citrobacter rodentium-mediated
      enteropathy in a mouse model.
AB  - The present work was aimed at investigating whether Bacillus subtilis spores,
      widely used in probiotic as well as pharmaceutical preparations for mild
      gastrointestinal disorders, can suppress enteric infections. To address this
      issue, we developed a mouse model of infection using the mouse enteropathogen
      Citrobacter rodentium, a member of a family of human and animal pathogens which
      includes the clinically significant enteropathogenic (EPEC) and enterohemorrhagic
      (EHEC) Escherichia coli strains. This group of pathogens causes transmissible
      colonic hyperplasia by using attaching and effacing (A/E) lesions to colonize the
      host colon. Because of its similarities to human enteropathogens, C. rodentium is
      now widely used as an in vivo model for gastrointestinal infections. Swiss NIH
      mice were orally administered B. subtilis spores one day before infection with C.
      rodentium. Mice were sacrificed on day 15 after infection, and distal colon,
      liver and mesenteric lymph nodes were removed for bacteria counts, morphology,
      immunohistology and IFNgamma mRNA analysis. We observed that spore predosing was
      effective in significantly decreasing infection and enteropathy in suckling mice
      infected with a dose of C. rodentium sufficient to cause colon colonization,
      crypt hyperplasia and high mortality rates. Moreover, in mice predosed with
      spores, the number of CD4(+) cells and IFNgamma transcript levels remained high.
      These results thus indicate that our newly established model of C. rodentium
      infection is a suitable system for analyzing the effects of probiotic bacteria on
      enteroinfections and that B. subtilis spores are efficient at reducing C.
      rodentium infection in mice, leaving unaltered the immune response against the
      pathogen.

PMID- 17005379
TI  - The type II signal peptidase of Legionella pneumophila.
AB  - Legionella pneumophila is a facultative intracellular Gram-negative bacterium
      that has become an important cause of community-acquired and nosocomial
      pneumonia. Recent studies concerning the unravelling of bacterial virulence have
      suggested the involvement of protein secretion systems in bacterial
      pathogenicity. In this respect, the type II signal peptidase (LspA), which is
      specifically required for the maturation of lipoproteins, is of particular
      interest. This paper reports the cloning and functional characterization of the
      L. pneumophila lspA gene encoding the type II signal peptidase (SPase II).
      Activity of the L. pneumophila LspA was demonstrated using a globomycin
      sensitivity assay in Escherichia coli. In L. pneumophila, the lspA gene is
      flanked by the isoleucyl-tRNA synthetase (ileS) gene and the gene encoding a 2
      hydroxy-3-deoxy-phosphogluconate aldolase. Although there is no apparent
      physiological connection, transcriptional analysis demonstrated that, as in some
      other Gram-negative bacteria, lspA is cotranscribed with ileS in L. pneumophila.
      Finally, in silico analysis revealed that several proteins known to be crucial
      for virulence and intracellular growth of L. pneumophila are predicted to be
      lipoproteins. These include, in particular, proteins involved in protein
      secretion and motility. Results obtained strongly suggest an important role for
      LspA in the pathogenicity of L. pneumophila, making it a promising new target for
      therapeutic intervention.

PMID- 17005380
TI  - Exopolysaccharides produced by the recently described halophilic bacteria
      Halomonas ventosae and Halomonas anticariensis.
AB  - We studied exopolysaccharides (EPSs) produced by Halomonas ventosae and Halomonas
      anticariensis, two novel species of halophilic bacteria. Under optimum
      environmental and nutritional conditions, H. ventosae strains Al12(T) and Al16
      excreted 28.35 mg and 28.95 mg of EPS per 100 ml of culture medium (34.55 and
      38.6 mg of EPS per gram of dry cell weight) respectively. The molecular masses of
      the polymers were about 50 kDa and their main components were glucose, mannose
      and galactose. They had high protein fractions and showed emulsifying activity on
      several hydrophobic substrates. Under optimum environmental and nutritional
      conditions, H. anticariensis strains FP35(T) and FP36 excreted about 29.65 and
      49.95 mg of EPS per 100 ml of culture medium (43.6 and 50.95 mg of EPS per gram
      of dry cell weight) respectively. The molecular masses of the polymers were about
      20 and 46 kDa respectively and were composed mainly of glucose, mannose and
      galacturonic acid. All EPSs produced solutions of low viscosity and pseudoplastic
      behaviour. They also had a high capacity for binding cations and incorporated
      considerable quantities of sulphates, which is highly unusual in bacterial
      polysaccharides. All strains assayed formed biofilms both in polystyrene wells
      and borosilicate test tubes.

PMID- 17005381
TI  - Non-viral gene therapy for Duchenne muscular dystrophy: progress and challenges.
AB  - Duchenne muscular dystrophy (DMD) is one of the most common lethal, hereditary
      diseases of childhood. Since the identification of the genetic basis of this
      disorder, there has been the hope that a cure would be developed in the form of
      gene therapy. This has yet to be realized, but many different gene therapy
      approaches have seen dramatic advances in recent years. Although viral-mediated
      gene therapy has been at the forefront of the field, several non-viral gene
      therapy approaches have been applied to animal and cellular models of DMD. These
      include plasmid-mediated gene delivery, antisense-mediated exon skipping, and
      oligonucleotide-mediated gene editing. In the past several years, non-viral gene
      therapy has moved from the laboratory to the clinic. Advances in vector design,
      formulation, and delivery are likely to lead to even more rapid advances in the
      coming decade. Given the relative simplicity, safety, and cost-effectiveness of
      these methodologies, non-viral gene therapy continues to have great promise for
      future gene therapy approaches to the treatment of DMD.

PMID- 17005382
TI  - 3D inverted opal hydrogel scaffolds with oxygen sensing capability.
AB  - The measurement of local oxygen level in 3D cell culture is desired but remains
      as a challenge problem. We developed a 3D cell scaffold with luminescence-based
      oxygen sensing capability that opens the possibility of 3D mapping of oxygen
      level during cell growth. Hydrogel inverted opal scaffold was prepared by photo
      polymerization of poly(2-hydroxyethyl methacrylate (pHEMA) and
      poly(methacryloyloxy)ethyl-trimethylammonium chloride (pMEATAC) monomer using
      close-packed bead assembly as template. Tris(4,7-diphenyl-1,10
      phenanthroline)ruthenium chloride (Ru(dpp)(3)), was coated on the pHEMA-pMEATAC
      3D scaffolds by layer-by-layer (LBL) assembly. pHEMA-pMEATAC copolymer was coated
      on top of the Ru(dpp)(3) layer as a protection layer. The fluorescence emission
      of Ru(dpp)(3) can be dynamically quenched by oxygen. By measuring the emission
      intensity of the scaffold, the local oxygen level can be monitored. The hydrogel
      scaffolds are transparent, and thus 3D fluorescence intensity can be mapped by
      confocal microscopy. Human bone marrow stromal cells HS-5 were successfully
      cultured on the oxygen sensing scaffold, and the observed Ru(dpp)(3) emission
      intensity from the scaffold was stronger in cell rich area, which indicates a
      lower oxygen level due to the consumption of the cells.

PMID- 17005384
TI  - Modelling of long-term dynamic leaching tests applied to solidified/stabilised
      waste.
AB  - The paper aims at simulating the closed-system dynamic leaching of a cement-based
      monolith containing lead with the numerical reactive transport code HYTEC in a 3D
      cylindrical geometry. The model considers, simultaneously, the chemical evolution
      of pore water, the progression of mineralogical alteration fronts, and the
      concomitant release of elements from the S/S waste. In good agreement with the
      experiment, element releases were found to be mainly controlled by either
      diffusion (Na, K, and, to a lesser extent, Cl), by surface dissolution (Ca, Si)
      or by a mixed evolution (Pb, SO4). All of the calculated mineralogical
      transformations take place in a thin layer beyond the monolith surface.
      Consequently, modelling of Ca, Si and SO4 releases was quite sensitive to the
      node size of the simulation grid and was improved by taking into account the
      increase of porosity and effective diffusion coefficient due to mineral
      dissolution in the leached layer. In agreement with experimental results, the
      deepest front corresponds under closed-system conditions to portlandite
      dissolution and calcium silicate hydrates CSH 1.8 transformation into CSH of
      lower Ca/Si ratio. A second, distinct and intermediate, front is made by
      ettringite dissolution. The network of CSH is globally preserved in the leached
      layer, complete dissolution occurring over a very small thickness only. Finally,
      hydrotalcite precipitation in the leached layer is expected by modelling due to
      pH drop.

PMID- 17005383
TI  - Influence of moisture content on the mechanical properties of methyl methacrylate
      starch copolymers.
AB  - The water vapour sorption-desorption behaviour of graft copolymers
      (hydroxypropylstarch-methyl methacrylate -HSMMA- and carboxymethylstarch-methyl
      methacrylate -CSMMA-) synthetised by free-radical polymerisation and
      alternatively dried by oven (OD) or freeze-drying (FD) techniques was
      investigated in a previous paper. The aim of the present study was to analyse the
      influence of the amount and distribution of water molecules on the flow and
      compaction characteristics of this family of methyl methacrylate-starch
      copolymers. Products were stored at constant temperature (25 degrees C) and
      different relative humidity conditions (RH). Flow properties of the powdered
      materials were evaluated using glass and stainless-steel funnels and the
      densification behaviour was studied in detail by means of Heckel treatment and
      compression parameters. Results revealed that the storage at 25-50% RH was the
      optimum condition relating flowability for HSMMA and OD-CSMMA copolymers. At
      higher RH values, the flow characteristics worsened, due to an increment in
      cohesive forces. Compaction experiments showed that the 25-50% RH range improved
      also the compression performance of the copolymers, due to increasing powder
      compressibility and reduced compact relaxation. Under these circumstances,
      absorbed water might act as plasticiser and adsorbed water as lubricant.

PMID- 17005385
TI  - Evaluation of leachate emissions from crushed rock and municipal solid waste
      incineration bottom ash used in road construction.
AB  - Three years of leachate emissions from municipal solid waste incineration bottom
      ash and crushed rock in a full-scale test road were evaluated. The impact of
      time, construction design, and climate on the emissions was studied, and the
      predicted release from standard leaching tests was compared with the measured
      release from the road. The main pollutants and their respective concentrations in
      leachate from the roadside slope were Al (12.8-85.3 mg l(-1)), Cr (2-125 microg
      l(-1)), and Cu (0.15-1.9 mg l(-1)) in ash leachate and Zn (1-780 microg l(-1)) in
      crushed rock leachate. From the ash, the initial Cl(-) release was high (
      approximately 20 g l(-1)). After three years, the amount of Cu and Cl(-) was in
      the same range in both leachates, while that of Al and Cr still was more than one
      order of magnitude higher in ash leachate. Generally, the release was faster from
      material in the uncovered slopes than below the pavement. Whether the road was
      asphalted or not, however, had minor impacts on the leachate quality. During rain
      events, diluted leachates with respect to, e.g., salts were observed. The
      leaching tests failed to simulate field leaching from the crushed rock, whereas
      better agreement was observed for the ash. Comparisons of constituent release
      from bottom ash and conventional materials solely based on such tests should be
      avoided.

PMID- 17005386
TI  - Use of a biologically active cover to reduce landfill methane emissions and
      enhance methane oxidation.
AB  - Biologically-active landfill cover soils (biocovers) that serve to minimize CH4
      emissions by optimizing CH4 oxidation were investigated at a landfill in Florida,
      USA. The biocover consisted of 50 cm pre-composted yard or garden waste placed
      over a 10-15 cm gas distribution layer (crushed glass) over a 40-100 cm interim
      cover. The biocover cells reduced CH4 emissions by a factor of 10 and doubled the
      percentage of CH4 oxidation relative to control cells. The thickness and moisture
      holding capacity of the biocover resulted in increased retention times for
      transported CH4. This increased retention of CH4 in the biocover resulted in a
      higher fraction oxidized. Overall rates between the two covers were similar,
      about 2g CH4 m(-2)d(-1), but because CH4 entered the biocover from below at a
      slower rate relative to the soil cover, a higher percentage was oxidized. In
      part, methane oxidation controlled the net flux of CH4 to the atmosphere. The
      biocover cells became more effective than the control sites in oxidizing CH4 3
      months after their initial placement: the mean percent oxidation for the biocover
      cells was 41% compared to 14% for the control cells (p<0.001). Following the
      initial 3 months, we also observed 29 (27%) negative CH4 fluxes and 27 (25%) zero
      fluxes in the biocover cells but only 6 (6%) negative fluxes and 22 (21%) zero
      fluxes for the control cells. Negative fluxes indicate uptake of atmospheric CH4.
      If the zero and negative fluxes are assumed to represent 100% oxidation, then the
      mean percent oxidation for the biocover and control cells, respectively, for the
      same period would increase to 64% and 30%.

PMID- 17005387
TI  - A decision support system for the operational planning of solid waste collection.
AB  - This study presents the conception, modeling, and implementation of a decision
      support system applied to the operational planning of solid waste collection
      systems, called SCOLDSS. The main functionality of the system is the generation
      of alternatives to the decision processes concerning: (a) the allocation of
      separate collection vehicles, as well as the determination of their routes and
      (b) the determination of the daily amount of solid waste to be sent to each
      sorting unit, in order to avoid waste of labor force and to reduce the amount of
      waste sent to the landfills. To develop the computer system, a combination of
      quantitative techniques was used, such as: simulation of discrete events and
      algorithms/heuristics for vehicle allocation and routing. The system was
      developed using the Borland Delphi environment and the commercial software Arena
      to carry out the simulations. We also present a computational study with real
      life data from the solid waste collection in Porto Alegre, Brazil, in which we
      show that the results provided by the computational system outperform the
      operation planning currently adopted.

PMID- 17005388
TI  - Characteristics of steel slag under different cooling conditions.
AB  - Four types of steel slags, a ladle slag, a BOF (basic oxygen furnace) slag and
      two different EAF (electric arc furnace) slags, were characterized and modified
      by semi-rapid cooling in crucibles and rapid cooling by water granulation. The
      aim of this work was to investigate the effect of different cooling conditions on
      the properties of glassy slags with respect to their leaching and volume
      stability. Optical microscopy, X-ray diffraction, scanning electron microscope
      and a standard test leaching (prEN 12457-2/3) have been used for the
      investigation. The results show that the disintegrated ladle slag was made volume
      stable by water granulation, which consisted of 98% glass. However EAF slag 1,
      EAF slag 2 and the BOF slag formed 17%, 1% and 1% glass, respectively. The
      leaching test showed that the glass-containing matrix did not prevent leaching of
      minor elements from the modified slags. The solubility of chromium, molybdenum
      and vanadium varied in the different modifications, probably due to their
      presence in different minerals and their different distributions.

PMID- 17005389
TI  - Prospects for applications of lanthanide-based upconverting surfaces to bioassay
      and detection.
AB  - Biological assays to detect binding interactions are often conducted using
      fluorescence resonance energy transfer (FRET) but this has several disadvantages
      that markedly reduce the dynamic range of measurements. The very short range of
      FRET interactions also causes difficulties when large analytes such as viruses or
      spores are to be detected. Conventional FRET-based assays can in principle be
      improved using infrared-excited upconverting lanthanide-based energy donors but
      this does not address the short range of the FRET process. Here we investigate an
      alternative mode of energy transfer based on evanescent wave coupling from an
      erbium-doped waveguide to an absorbed fluorophore and characterise the
      luminescence from the dopant. The upconverted erbium emission is highly
      structured with well-separated bands in the violet, green and red spectral
      regions and very little detectable signal between the peaks. The relative
      intensity of these bands depends on power-density of infrared excitation. Green
      emission predominates at low power-density and red emission increases more
      rapidly as power-density increases, with a smaller violet peak also emerging. The
      temporal response of the upconverting material to pulsed infrared excitation was
      investigated and was shown to vary markedly with emission wavelength with the red
      component being particularly sensitive to the duration of the excitation pulse. A
      surface monolayer of the fluorescent protein R-phycoerythrin was very easily
      detected on binding to an upconverting waveguide. The potential advantages and
      limitations of the evanescent wave excitation technique for fluorescence
      detection are discussed and avenues for further development are considered.

PMID- 17005390
TI  - Epigenetic variation and inheritance in mammals.
AB  - What determines phenotype is one of the most fundamental questions in biology.
      Historically, the search for answers had focused on genetic or environmental
      variants, but recent studies in epigenetics have revealed a third mechanism that
      can influence phenotypic outcomes, even in the absence of genetic or
      environmental heterogeneity. Even more surprisingly, some epigenetic variants, or
      epialleles, can be inherited by the offspring, indicating the existence of a
      mechanism for biological heredity that is not based on DNA sequence. Recent work
      from mouse models, human monozygotic twin studies, and large-scale epigenetic
      profiling suggests that epigenetically determined phenotypes and epigenetic
      inheritance are more common than previously appreciated.

PMID- 17005391
TI  - Coevolution, modularity and human disease.
AB  - The concepts of coevolution and modularity have been studied separately for
      decades. Recent advances in genomics have led to the first systematic studies in
      each of these fields at the molecular level, resulting in several important
      discoveries. Both coevolution and modularity appear to be pervasive features of
      genomic data from all species studied to date, and their presence can be detected
      in many types of datasets, including genome sequences, gene expression data, and
      protein-protein interaction data. Moreover, the combination of these two ideas
      might have implications for our understanding of many aspects of biology, ranging
      from the general architecture of living systems to the causes of various human
      diseases.

PMID- 17005392
TI  - Global analysis of gene expression in the estrogen induced pituitary tumor of the
      F344 rat.
AB  - The F344 rat rapidly forms large prolactinomas in response to chronic estrogen
      treatment. To identify genes expressed in the course of this estrogen induced
      pituitary tumor growth, we performed microarray analysis on the F344 rat
      pituitary after chronic estrogen treatment and on untreated controls. At a
      significance level set to minimize type I error, some 72 genes were found to be
      differentially expressed between estrogen treated and untreated. Of those genes,
      70 have not been reported previously as being affected by estrogen in the F344
      rat pituitary. Since many other investigators have studied the effect of estrogen
      on specific gene expression in rat pituitary, we also examined the mRNA
      expression of the 36 genes that have been previously reported as having their
      expression affected by estrogen in the rat pituitary. Of these, 13 were found to
      have their expression affected by estrogen treatment in the same direction as had
      been reported by others.

PMID- 17005393
TI  - Tetrahydroisoquinoline PPARgamma agonists: design of novel, highly selective non
      TZD antihyperglycemic agents.
AB  - Novel tetrahydroisoquinolines have been developed as potent PPAR ligands.
      Evaluation of these compounds in PPARgamma responsive models of type 2 diabetes
      is described.

PMID- 17005394
TI  - Synthesis and evaluation of aminomethyl dihydrocinnamates as a new class of PPAR
      ligands.
AB  - PPAR ligands with varied subtype selectivity have been synthesized using an
      achiral aminomethyl dihydrocinnamate template. Several compounds in this series
      have demonstrated potent plasma glucose and triglyceride lowering capability in
      rodent models of type 2 diabetes.

PMID- 17005395
TI  - Membrane targeted chemotherapy with hybrid liposomes for colon tumor cells
      leading to apoptosis.
AB  - A good correlation between 50% inhibitory concentration of hybrid liposomes (HL)
      composed of 90 mol% dimyristoylphosphatidylcholine and 10 mol%
      polyoxyethylene(n)dodecyl ether on the growth of human colon tumor (WiDr) cells,
      and membrane fluidity of HL was obtained. HL distinguished between WiDr and
      normal colon cells and then fused and accumulated into the membranes of WiDr
      cells leading to apoptosis.

PMID- 17005396
TI  - Extreme phenotypic variability in a German family with X-linked myotubular
      myopathy associated with E404K mutation in MTM1.
AB  - X-linked myotubular myopathy (XLMTM) is a congenital muscle disorder caused by
      mutations in the MTM1 gene. Affected males usually present at birth with severe
      hypotonia and respiratory insufficiency, and most of them die within the first
      few years of life. We report here on a 68-year-old patient with a very mild form
      of the disease who was diagnosed after his grandson showed muscular weakness and
      respiratory problems at birth. The E404K mutation in the MTM1 gene was found in
      both patients. To our knowledge, this grandfather is one of the oldest and most
      mildly affected known patients with an MTM1 mutation to date. Thus, this family
      represents a remarkable phenotypic variation of XLMTM ranging from a congenital
      to a mild adult form.

PMID- 17005397
TI  - No effect of folic acid and methionine supplementation on D4Z4 methylation in
      patients with facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is associated with a contraction of
      the D4Z4 allele on chromosome 4qter. There is also marked DNA hypomethylation of
      the D4Z4 allele. The DNA hypomethylation may have a central role in the
      pathogenesis of FSHD. Supplemental folic acid can boost DNA methylation. We
      evaluated the effect of oral folic acid and methionine supplementation on the
      methylation level of 4qter D4Z4 alleles in peripheral-blood lymphocytes of nine
      patients affected with FSHD and six healthy controls. Methylation levels did not
      change, while recommended serum-folate concentrations were reached.

PMID- 17005398
TI  - Outpatient continuous inotrope infusion as an adjunct to heart failure therapy in
      Duchenne muscular dystrophy.
AB  - We report the use of continuous intravenous inotrope infusion as a palliative
      management strategy for the treatment of symptomatic, refractory, end stage
      cardiac dysfunction in patients with Duchenne muscular dystrophy. Milrinone
      and/or dobutamine administered by continuous intravenous infusion provided
      symptomatic and objective cardiovascular improvement up to 30 months in 3
      individuals with Duchenne muscular dystrophy and severe dilated cardiomyopathy.
      Continuous inotrope infusion should be considered a practical treatment strategy
      for end stage cardiac dysfunction in Duchenne muscular dystrophy patients when
      cardiac transplantation is not a viable option.

PMID- 17005399
TI  - Myopathy in horses with pituitary pars intermedia dysfunction (Cushing's
      disease).
AB  - Fifteen horses with pituitary pars intermedia dysfunction were studied. The
      horses were of various breeds and between 15 and 28 years of age. Control horses
      matched for breed and age were studied for comparison. Evaluations included
      complete blood cell count and serum biochemical analysis, electromyography, and
      gluteus medius muscle biopsies for histochemical, morphometric, and
      ultrastructural analysis. No differences were found between groups of horses on
      routine laboratory analysis or electromyography. We demonstrated that muscle
      wasting in diseased horses was the result of atrophy of types 2A and 2B muscle
      fibers and loss of type 2B myofibers. Mild non-specific non-inflammatory
      myopathic alterations such as myofiber size variation, internal nuclei,
      perimysial, endomysial and sarcoplasmic fat accumulation were observed. At the
      ultrastructural level, subsarcolemmal mitochondrial accumulation and increased
      lipid droplets were evident. Similar to other species, this study confirmed
      atrophy of type 2 fibers as the cause of muscle mass loss in horses with
      Cushing's disease.

PMID- 17005400
TI  - Atypical presentation of macrophagic myofasciitis 10 years post vaccination.
AB  - Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle
      believed to be due to persistence of vaccine-derived aluminium hydroxide at the
      site of injection. The condition is characterised by diffuse myalgias, arthralgia
      and fatigue. We describe a patient with histologically confirmed MMF whose
      presentation was atypical with left chest and upper limb pain beginning more than
      10 years post vaccination. Treatment with steroids led to symptomatic
      improvement. Although rare, clinicians should consider MMF in cases of atypical
      myalgia.

PMID- 17005401
TI  - Myofibrillar myopathy with congenital cataract and skeletal anomalies without
      mutations in the desmin, alphaB-crystallin, myotilin, LMNA or SEPN1 genes.
AB  - Myofibrillar myopathies are genetically heterogeneous. We present a sporadic case
      of an 8-year-old boy with unusual combination of congenital skeletal muscle
      myopathy, cataract and poly/syndactyly. Muscle pathology revealed a mild
      myopathic picture with hyaline plaques, showing dark green staining in modified
      trichrome reaction, and strong immunoreactivity for alphaB-crystallin, desmin and
      dystrophin. Analysis of the coding sequences of the desmin, alphaB-crystallin,
      SEPN1, lamin A/C genes and of exon 2 of the myotilin gene showed no abnormalities
      in the patient. Presented case expands the wide clinical spectrum of myofibrillar
      myopathies, reinforcing the need for further exploration of genetic causes for
      this group of disorders.

PMID- 17005402
TI  - Muscle cell and motor protein function in patients with a IIa myosin missense
      mutation (Glu-706 to Lys).
AB  - The pathogenic events leading to the progressive muscle weakness in patients with
      a E706K mutation in the head of the myosin heavy chain (MyHC) IIa were analyzed
      at the muscle cell and motor protein levels. Contractile properties were measured
      in single muscle fiber segments using the skinned fiber preparation and a single
      muscle fiber in vitro motility assay. A dramatic impairment in the function of
      the IIa MyHC isoform was observed at the motor protein level. At the single
      muscle fiber level, on the other hand, a general decrease was observed in the
      number of preparations where the specific criteria for acceptance were fulfilled
      irrespective of MyHC isoform expression. Our results provide evidence that the
      pathogenesis of the MyHC IIa E706K myopathy involves defective function of the
      mutated myosin as well as alterations in the structural integrity of all muscle
      cells irrespective of MyHC isoform expression.

PMID- 17005403
TI  - Premature proliferative arrest of cricopharyngeal myoblasts in oculo-pharyngeal
      muscular dystrophy: Therapeutic perspectives of autologous myoblast
      transplantation.
AB  - Cultures of myoblasts isolated from cricopharyngeal muscles from patients with
      oculopharyngeal muscular dystrophy (OPMD) have been performed to study the effect
      of the expanded (GCG)8-13 repeat, located on the poly(A) binding protein nuclear
      1 (PABPN1), on satellite cell phenotype. Cell cultures exhibited a reduced
      myogenicity, as well as a rapid decrease in proliferative lifespan, as compared
      to controls. The incorporation of BrdU decreased during the proliferative
      lifespan, due to a progressive accumulation of non-dividing cells. A lower fusion
      index was also observed, but myoblasts were able to form large myotubes when OPMD
      cultures were purified, although a rapid loss of myogenicity during successive
      passages was also observed. Myoblasts isolated from unaffected muscles did not
      show the defects observed in cricopharyngeal muscle cultures. The PABPN1 was
      predominantly located in nuclei of myoblasts and in both the nuclei and cytoplasm
      of myotubes in OPMD cultures. In vivo analysis of OPMD muscles showed that the
      number of satellite cells was slightly higher than that observed in age matched
      controls. Mutation of the PABPN1 in OPMD provokes premature senescence in
      dividing myoblasts, that may be due to intranuclear toxic aggregates. These
      results suggest that myoblast autografts, isolated from unaffected muscles, and
      injected into the dystrophic pharyngeal muscles, may be a useful therapeutic
      strategy to restore muscular function. Its tolerance and feasibility has been
      preclinically demonstrated in the dog.

PMID- 17005404
TI  - Streptomycin reduces stretch-induced membrane permeability in muscles from mdx
      mice.
AB  - It is well-known that muscles from mdx mice are more susceptible to membrane
      damage from eccentric contractions than wild-type muscles. The present study
      tested the hypothesis that the stretch-induced membrane permeability in
      dystrophic muscle is due to Ca(2+) entry through stretch-activated channels
      (SACs) and the subsequent activation of Ca(2+) -dependent degradative pathways.
      Eccentric contractions were carried out on muscles from mdx and wild-type mice,
      both on isolated muscles and on intact mice subjected to downhill running on a
      treadmill. In isolated muscles the SAC blockers, streptomycin and GsMTx4,
      improved force and significantly reduced the uptake of procion orange dye into
      fibres from mdx muscles, which increased progressively over 60 min after the
      eccentric contractions. In experiments on intact mdx mice, streptomycin also
      partially prevented the reduced force and the increased membrane permeability
      (Evans Blue Dye uptake). The results suggest that Ca(2+) entry through SACs
      activates Ca(2+) -dependent pathways, which are the main cause of the increased
      membrane permeability in mdx muscle.

PMID- 17005405
TI  - The multitalented microbial sensory rhodopsins.
AB  - Sensory rhodopsins are photoactive, membrane-embedded seven-transmembrane helix
      receptors that use retinal as a chromophore. They are widespread in the microbial
      world in each of the three domains of life: Archaea, Bacteria and Eukarya. A
      striking characteristic of these photoreceptors is their different modes of
      signaling in different organisms, including interaction with other membrane
      proteins, interaction with cytoplasmic transducers and light-controlled Ca(2+)
      channel activity. More than two decades since the discovery of the first sensory
      rhodopsins in the archaeon Halobacterium salinarum, genome projects have revealed
      a widespread presence of homologous photosensors. New work on cyanobacteria,
      algae, fungi and marine proteobacteria is revealing how evolution has modified
      the common design of these proteins to produce a remarkably rich diversity in
      their signaling biochemistry.

PMID- 17005406
TI  - New multipotent tetracyclic tacrines with neuroprotective activity.
AB  - The synthesis and the biological evaluation (neuroprotection, voltage dependent
      calcium channel blockade, AChE/BuChE inhibitory activity and propidium binding)
      of new multipotent tetracyclic tacrine analogues (5-13) are described. Compounds
      7, 8 and 11 showed a significant neuroprotective effect on neuroblastoma cells
      subjected to Ca(2+) overload or free radical induced toxicity. These compounds
      are modest AChE inhibitors [the best inhibitor (11) is 50-fold less potent than
      tacrine], but proved to be very selective, as for most of them no BuChE
      inhibition was observed. In addition, the propidium displacement experiments
      showed that these compounds bind AChE to the peripheral anionic site (PAS) of
      AChE and, consequently, are potential agents that can prevent the aggregation of
      beta-amyloid. Overall, compound 8 is a modest and selective AChE inhibitor, but
      an efficient neuroprotective agent against 70mM K(+) and 60microM H(2)O(2). Based
      on these results, some of these molecules can be considered as lead candidates
      for the further development of anti-Alzheimer drugs.

PMID- 17005407
TI  - A platform for designing HIV integrase inhibitors. Part 2: a two-metal binding
      model as a potential mechanism of HIV integrase inhibitors.
AB  - We propose a two-metal binding model as a potential mechanism of chelating
      inhibitors against HIV integrase (HIV IN) represented by 2-hydroxy-3-heteroaryl
      acrylic acids (HHAAs). Potential inhibitors would bind to two metal ions in the
      active site of HIV IN to prevent human DNA from undergoing the integration
      reaction. Correlation of the results of metal (Mg(2+) and Mn(2+)) titration
      studies with HIV IN inhibition for a series of active and inactive compounds
      provides support for the model. Results suggest Mg(2+) is an essential cofactor
      for chelating inhibitors.

PMID- 17005408
TI  - Extensive extracellular matrix depositions in active multiple sclerosis lesions.
AB  - In the central nervous system, basement membrane (BM) constituents are
      predominantly associated with the vasculature. However, under inflammatory
      conditions, the expression of BM components may alter. Here, we investigated the
      distribution of several BM components, including laminin, collagen type IV and
      heparan sulfate proteoglycans in various multiple sclerosis (MS) lesions. We
      observed irregular and discontinuous BMs in active lesions. Throughout active MS
      lesions, we found dense networks of BM proteins, which were surprisingly not
      associated with the cerebrovasculature. These striking parenchymal networks were
      not observed in chronic inactive MS lesions and brains of non-neurological
      controls. In addition, we studied the distribution of transforming growth factor
      beta1 (TGF-beta1), since it is known as a major modulator of ECM production.
      Leukocytes, in particular CD68-positive macrophages, expressed high levels of TGF
      beta1 and were located in close proximity to parenchymal BM deposits in the MS
      lesions. We postulate that these BM networks may play a role in the further
      recruitment of inflammatory cells and form a barrier for axonal regeneration.

PMID- 17005410
TI  - Cytokine gene polymorphisms involved in chronicity and complications of anterior
      uveitis.
AB  - The aim of this study was to identify key cytokine polymorphisms associated with
      disease susceptibility, clinical phenotype, and outcome in patients with chronic
      anterior uveitis (CAU) as compared to those with recurrent self-limiting anterior
      uveitis (RAU). One hundred fifty seven British Caucasian patients with anterior
      uveitis were identified and divided into those where the inflammatory process
      lasted less than 3 months (RAU=118) and those where the inflammation persisted
      longer than 3 months (CAU=39). Patients with CAU were further sub-divided into
      idiopathic CAU, CAU associated with systemic disease, CAU with and without
      complications (posterior synechiae, posterior subcapsular lens opacity, raised
      intraocular pressure, cystoid macular oedema, and poor response to treatment).
      Sixty-six healthy controls were ethnically matched. TaqMan PCR amplification was
      used to genotype five single nucleotide polymorphisms in cytokine genes; IL
      1RN+2018, IL-6-174, IL-10-1082, TNF-238, TNF-308 and these were correlated with
      clinical phenotype.

PMID- 17005411
TI  - Therapeutic targeting of cytokines.
AB  - Over recent years, with many advances in understanding the pathological processes
      that underlie many inflammatory conditions, it has become clear that targeting
      cytokines has proven to be highly effective therapeutically. The second
      International Cytokine symposium, held recently in Manchester UK, has provided an
      important forum for bringing basic and clinical scientists together to discuss
      many aspects of cytokine medicine from the laboratory to the clinic. In this
      article, we provide an overview of the main issues raised from this important
      conference and set the scene for more detailed reports that follow in subsequent
      articles in this journal.

PMID- 17005412
TI  - TNF-alpha inhibits adult fast myosin accumulation in myotubes.
AB  - Increased muscle catabolism is frequently observed in association with
      inflammatory disease. TNF-alpha has been implicated as an important messenger for
      muscle catabolism. Experiments with cultured muscle cells exposed to TNF-alpha
      have produced conflicting results. In a mouse cell line (C2C12), effects ranged
      from catabolic to anabolic. The results reported here offer an explanation for
      the observed discrepancies. It was found that TNF-alpha induced proliferation of
      myoblasts in fully differentiated cultures in low serum media and inhibited adult
      fast myosin accumulation under all conditions that were tested. Furthermore, TNF
      alpha caused a proliferation dependent increase in total cell protein. Addition
      of insulin masked the effect of TNF-alpha on total protein, but not that on adult
      fast myosin accumulation. Discrepancies between studies can be explained by
      differences in proliferation rate, the dynamic nature of C2C12 myotube cultures
      and accumulation of adult fast myosin. The results are consistent with a dual
      role of TNF-alpha: stimulation of regeneration by short-term exposure and
      induction of muscle wasting by prolonged exposure.

PMID- 17005413
TI  - NF-kappaB signaling pathway is involved in growth inhibition, G2/M arrest and
      apoptosis induced by Trichostatin A in human tongue carcinoma cells.
AB  - The HDAC inhibitor Trichostatin A (TSA) exhibits antitumour activity in various
      tumour cells. However, little is known about the effect of TSA on growth of human
      tongue carcinoma cells. In this study, we observed that TSA concentration
      dependently inhibited growth of human tongue carcinoma Tca8113 cells by inducing
      G2/M arrest, apoptosis, up-regulation of the pro-apoptotic protein Bax and down
      regulation of the anti-apoptotic proteins Bcl-2 and Bcl-XL which are regulated by
      the transcription factor nuclear factor (NF)-kappaB. Coincident with this
      observation, TSA induced a concentration-dependent reduction of constitutive and
      tumour necrosis factor (TNF)-alpha-induced NF-kappaB activation in Tca8113 cells.
      This induction was correlated with decreased phosphorylation and increased
      expression of inhibitors of NF-kappaB (IkappaB)alpha induced by TSA. Overall, our
      results indicate inhibition of NF-kappaB activation contributes, at least
      partially, to the antitumour activity of TSA in human tongue carcinoma cells.

PMID- 17005414
TI  - Gas phase noncovalent protein complexes that retain solution binding properties:
      Binding of xylobiose inhibitors to the beta-1, 4 exoglucanase from cellulomonas
      fimi.
AB  - Tandem mass spectrometry has been used to compare gas-phase and solution binding
      of three small-molecule inhibitors to the wild type and three mutant forms of the
      catalytic domain of Cex, an enzyme that hydrolyses xylan and xylo
      oligosaccharides. The inhibitors, xylobiosyl-deoxynojirimycin, xylobiosyl
      isofagomine lactam, and xylobiosyl-isofagomine consist of a common distal xylose
      linked to different proximal aza-sugars. The three mutant forms of the enzyme
      contain the substitutions Asn44Ala, Gln87Met, and Gln87Tyr that alter the binding
      interactions between Cex and the distal sugar of each inhibitor. An electrospray
      ionization (ESI) triple quadrupole MS/MS system is used to measure the internal
      energies, DeltaE(int), that must be added to gas-phase ions to cause dissociation
      of the noncovalent enzyme-inhibitor complexes. Collision cross sections of ions
      of the apo-enzyme and enzyme-inhibitor complexes, which are required for the
      calculations of DeltaE(int), have also been measured. The results show that, in
      the gas phase, enzyme-inhibitor complexes have more compact, folded conformations
      than the corresponding apo-enzyme ions. With the mutant enzymes, the effects of
      substituting a single residue can be detected. The energies required to
      dissociate the gas-phase complexes follow the same trend as the values of DeltaG0
      for dissociation of the complexes in solution. This trend is observed both with
      different inhibitors, which probe binding to the proximal sugar, and with mutants
      of Cex, which probe binding to the distal sugar. Thus the gas-phase complexes
      appear to retain much of their solution binding characteristics.

PMID- 17005415
TI  - Dehydration versus deamination of N-terminal glutamine in collision-induced
      dissociation of protonated peptides.
AB  - Some of the most prominent "neutral losses" in peptide ion fragmentation are the
      loss of ammonia and water from N-terminal glutamine. These processes are studied
      by electrospray ionization mass spectrometry in singly- and doubly-protonated
      peptide ions undergoing collision-induced dissociation in a triple quadrupole and
      in an ion trap instrument. For this study, four sets of peptides were
      synthesized: (1) QLLLPLLLK and similar peptides with K replaced by R, H, or L,
      and Q replaced by a number of amino acids, (2) QLnK (n = 0, 1, 3, 5, 7, 9, 11),
      (3) QLnR (n = 0, 1, 3, 5, 7, 9), and (4) QLn (n = 1, 2, 3, 4, 8). The results for
      QLLLPLLLK and QLLLPLLLR show that the singly protonated ions undergo loss of
      ammonia and to a smaller extent loss of water, whereas the doubly protonated ions
      undergo predominant loss of water. The fast fragmentation next to P (forming the
      y5 ion) occurs to a larger extent than the neutral losses from the singly
      protonated ions but much less than the water loss from the doubly protonated
      ions. The results from these and other peptides show that, in general, when N
      terminal glutamine peptides have no "mobile protons", that is, the number of
      charges on the peptide is no greater than the number of basic amino acids (K, R,
      H), deamination is the predominant neutral loss fragmentation, but when mobile
      protons are present the predominant process is the loss of water. Both of these
      processes are faster than backbone fragmentation at the proline. These results
      are rationalized on the basis of resonance stabilization of the two types of five
      membered ring products that would be formed in the neutral loss processes; the
      singly protonated ion yields the more stable neutral pyrrolidinone ring whereas
      the doubly protonated ion yields the protonated aminopyrroline ring (see
      Schemes). The generality of these trends is confirmed by analyzing an MS/MS
      spectra library of peptides derived from tryptic digests of yeast. In the absence
      of mobile protons, glutamine deamination is the most rapid neutral loss process.
      For peptides with mobile protons, dehydration from glutamine is far more rapid
      than from any other amino acid. Most strikingly, end terminal glutamine is by far
      the most labile source of neutral loss in excess-proton peptides, but not highly
      exceptional when mobile protons are not available. In addition, rates of
      deamination are faster in lysine versus arginine C-terminus peptides and 20 times
      faster in positively charged than negatively charged peptides, demonstrating that
      these formal neutral loss reactions are not "neutral reactions" but depend on
      charge state and stability.

PMID- 17005416
TI  - In situ structural characterization of glycerophospholipids and sulfatides in
      brain tissue using MALDI-MS/MS.
AB  - Lipids are major structural components of biomembranes. Negatively charged
      species such as phosphatidylinositol, phosphatidylserine, sulfatides, and the
      zwitterionic phosphatidylethanolamines are major components of the cytoplasmic
      surface of the cellular membrane lipid bilayer and play a key role in several
      receptors signaling functions. Lipids are not just involved in metabolic and
      neurological diseases; negatively charged lipids in particular play crucial roles
      in physiological events such as signal transduction, receptors, and enzymatic
      activation, as well as storage and release of therapeutic drugs and toxic
      chemicals in the body. Due to the importance of their role in signaling, the
      field of lipidomics has rapidly expanded in recent years. In the present study,
      direct probing of tissue slices with negative ion mode matrix assisted laser
      desorption/ionization mass spectrometry was employed to profile the distribution
      of lipids in the brain. In total, 32 lipid species consisting of
      phosphatidylethanolamines, phosphatidylglycerol, phosphatidylinositols,
      phosphatidylserines, and sulfatides were assigned. To confirm the structure of
      lipid species, MALDI-MS/MS analysis was conducted. Product-ion spectra obtained
      in negative ion mode allow for the assignment of the head groups and the fatty
      acid chains for the lipid species.

PMID- 17005418
TI  - Expression and characterization of alpha-(1,4)-glucan branching enzyme Rv1326c of
      Mycobacterium tuberculosis H37Rv.
AB  - Glycogen branching enzyme (GlgB, EC 2.4.1.18) catalyzes the third step of
      glycogen biosynthesis by the cleavage of an alpha-(1,4)-glucosidic linkage and
      subsequent transfer of cleaved oligosaccharide to form a new alpha-(1,6)-branch.
      A single glgB gene Rv1326c is present in Mycobacterium tuberculosis. The
      predicted amino acid sequence of GlgB of M. tuberculosis has all the conserved
      regions of alpha-amylase family proteins. The overall amino acid identity to
      other GlgBs ranges from 48.5 to 99%. The glgB gene of M. tuberculosis was cloned
      and expressed in Escherichia coli. The recombinant protein was purified to
      homogeneity using metal affinity and ion exchange chromatography. The recombinant
      protein is a monomer as evidenced by gel filtration chromatography, is active as
      an enzyme, and uses amylose as the substrate. Enzyme activity was optimal at pH
      7.0, 30 degrees C and divalent cations such as Zn2+ and Cu2+ inhibited activity.
      CD spectroscopy, proteolytic cleavage and mass spectroscopy analyses revealed
      that cysteine residues of GlgB form structural disulfide bond(s), which allow the
      protein to exist in two different redox-dependent conformational states. These
      conformations have different surface hydrophobicities as evidenced by ANS
      fluorescence of oxidized and reduced GlgB. Although the conformational change did
      not affect the branching enzyme activity, the change in surface hydrophobicity
      could influence the interaction or dissociation of different cellular proteins
      with GlgB in response to different physiological states.

PMID- 17005417
TI  - Secondary structure and 3D homology modeling of grass carp (Ctenopharyngodon
      idellus) major histocompatibility complex class I molecules.
AB  - No information to date is available on the structure of fish major
      histocompatibility complex (MHC) class I and beta2-microglobulin (beta2m)
      proteins. In the present study, grass carp (Ctenopharyngodon idellus) MHC class I
      (Ctid-MHC I) and beta(2)-microglobulin (Ctid-beta2m) genes were expressed as
      soluble maltose binding protein (MBP)-proteins and purified in a pMAL
      p2X/Escherichia coli TB1 system. The expressed proteins were purified on amylase
      affinity columns followed by DEAE-Sepharose. The purified products were
      identified by Western blotting with anti-MBP polyclonal antibodies. The MBP-Ctid
      MHC I and MBP-Ctid-beta2m were cleaved separately with Factor Xa, mixed together
      and purified on DEAE-Sepharose. The secondary structures were analyzed by
      circular dichroism (CD) spectrophotometry. The three-dimensional (3D) structure
      of their peptide-binding domain (PBD) was modeled based sequence homology. The
      sequence lengths of the alpha-helix, beta-sheet, turn, and random coil in the
      Ctid-MHC I protein were 79aa, 75aa, 20aa, and 99aa, respectively. In the 97aa of
      Ctid-beta2m, the contents of the alpha-helix, beta-sheet, turn, and random coil
      were 0aa, 41aa, 12aa, and 44aa, respectively. The Ctid-beta2m protein displayed a
      typical beta-sheet. Homology modeling of the Ctid-MHC I and Ctid-beta2m proteins
      demonstrated similarities with the structure of human MHC class I proteins.

PMID- 17005419
TI  - Optimisation of production of a domoic acid-binding scFv antibody fragment in
      Escherichia coli using molecular chaperones and functional immobilisation on a
      mesoporous silicate support.
AB  - Domoic acid is a potent neurotoxin that can lead to amnesic shellfish poisoning
      in humans through ingestion of contaminated shellfish. We have produced and
      purified an anti-domoic acid single-chain Fragment variable (scFv) antibody
      fragment from the Escherichia coli periplasm. Yields of functional protein were
      increased by up to 100-fold upon co-production of E. coli DnaKJE molecular
      chaperones but co-overproduction of GroESL led to a reduction in solubility of
      the scFv. Co-production of the peptidyl-prolyl isomerase trigger factor resulted
      in accumulation of unprocessed scFv in the E. coli cytoplasm. This was due to an
      apparent bottleneck in translocation of the cytoplasmic membrane by the
      recombinant polypeptide. Co-expression of the E. coli disulfide bond isomerase
      dsbC increased scFv yields by delaying lysis of the host bacterial cells though
      this effect was not synergistic with molecular chaperone co-production.
      Meanwhile, use of a cold-shock promoter for protein production led to
      accumulation of greater amounts of scFv polypeptide which was predominantly in
      insoluble form and could not be rescued by chaperones. Purification of the scFv
      was achieved using an optimised metal affinity chromatography procedure and the
      purified protein bound domoic acid when immobilised on a mesoporous silicate
      support. The work outlines the potential benefit of applying a molecular
      chaperone/folding catalyst screening approach to improve antibody fragment
      production for applications such as sensor development.

PMID- 17005420
TI  - The effect of gender on planning: An fMRI study using the Tower of London task.
AB  - Since the introduction of brain mapping, evidences of functional gender
      differences have been corroborating previous behavioral and neuropsychological
      results showing a sex-specific brain organization. We investigated gender
      differences in brain activation during the performance of the Tower of London
      (TOL) task which is a standardized test to assess executive functions. Eighteen
      healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a
      series of TOL problems with different levels of difficulty. Data were analyzed by
      modeling both genders and difficulty task load. Task-elicited brain activations
      comprised a bilateral fronto-parietal network, common to both genders; within
      this network, females activated more than males in dorsolateral prefrontal cortex
      (DLPFC) and right parietal cortex, whereas males showed higher activity in
      precuneus. A prominent parietal activity was found at low level of difficulty
      while, with heavier task demand, several frontal regions and subcortical
      structures were recruited. Our results suggest peculiar gender strategies, with
      males relying more on visuospatial abilities and females on executive processing.

PMID- 17005422
TI  - What about us? Siblings of children with epilepsy.
AB  - RATIONALE: It is known that epilepsy has a severe impact in the quality of life
      of the patients; however, it affects the lives of all family members. The
      psychosocial repercussions of epilepsy are often of greater significance than the
      seizures themselves. METHODS: This was a prospective study, conducted from
      January 2005 to December 2005 at the pediatric epilepsy clinic of our University
      Hospital. Parents were interviewed by one of the authors according to a
      structured questionnaire about the impact of epilepsy in the life of the siblings
      of children with epilepsy. RESULTS: One hundred and twenty-seven children,
      siblings of 78 patients with epilepsy were evaluated. From the 127 siblings of
      children with epilepsy, 60 were girls and 67 were boys. Ages ranged from 5 to 18
      years old (mean=11.7 years). After the diagnosis of epilepsy, the siblings had
      only negative feelings toward the disease, mostly sadness and fear. CONCLUSION:
      Our data showed that the impact of epilepsy in the lives of siblings of children
      with epilepsy is much more severe than previously suspected.

PMID- 17005421
TI  - Phylogenetic relationships, host affinity, and geographic structure of boreal and
      arctic endophytes from three major plant lineages.
AB  - Although associated with all plants, fungal endophytes (microfungi that live
      within healthy plant tissues) represent an unknown proportion of fungal
      diversity. While there is a growing appreciation of their ecological importance
      and human uses, little is known about their host specificity, geographic
      structure, or phylogenetic relationships. We surveyed endophytic Ascomycota from
      healthy photosynthetic tissues of three plant species (Huperzia selago, Picea
      mariana, and Dryas integrifolia, representing lycophytes, conifers, and
      angiosperms, respectively) in northern and southern boreal forest (Quebec,
      Canada) and arctic tundra (Nunavut, Canada). Endophytes were recovered from all
      plant species surveyed, and were present in <1-41% of 2 mm2 tissue segments
      examined per host species. Sequence data from the nuclear ribosomal internal
      transcribed spacer region (ITS) were obtained for 280 of 558 isolates. Species
      accumulation curves based on ITS genotypes remained non-asymptotic, and bootstrap
      analyses indicated that a large number of genotypes remain to be found. The
      majority of genotypes were recovered from only a single host species, and only 6%
      of genotypes were shared between boreal and arctic communities. Two independent
      Bayesian analyses and a neighbor-joining bootstrapping analysis of combined data
      from the nuclear large and small ribosomal subunits (LSUrDNA, SSUrDNA; 2.4 kb)
      showed that boreal and arctic endophytes represent Dothideomycetes,
      Sordariomycetes, Chaetothyriomycetidae, Leotiomycetes, and Pezizomycetes. Many
      well-supported phylotypes contained only endophytes despite exhaustive sampling
      of available sequences of Ascomycota. Together, these data demonstrate greater
      than expected diversity of endophytes at high-latitude sites and provide a
      framework for assessing the evolution of these poorly known but ubiquitous
      symbionts of living plants.

PMID- 17005423
TI  - mTOR signaling in the hippocampus is necessary for memory formation.
AB  - It is widely accepted that the formation of long-term memory (LTM) requires mRNA
      translation, but little is known about the cellular mechanisms in the brain that
      regulate this process. Mammalian target of rapamycin (mTOR) is a key regulator of
      translational efficacy and capacity. Here, we show that LTM formation of one
      trial inhibitory avoidance (IA) in rats, a hippocampus-dependent fear-motivated
      learning task, requires mTOR activation. IA training is specifically associated
      with a rapid increase in the phosphorylation state of mTOR and its substrate
      ribosomal S6 kinase (p70S6K). Bilateral intra-CA1 infusion of rapamycin, a
      selective mTOR inhibitor, 15 min before, but not immediately after training
      completely hinders IA LTM without affecting short-term memory (STM) retention.
      Therefore, our findings indicate that the regulation of hippocampal mRNA
      translation is a major control step in memory consolidation.

PMID- 17005424
TI  - Hexose uptake in the plant symbiotic ascomycete Tuber borchii Vittadini:
      biochemical features and expression pattern of the transporter TBHXT1.
AB  - Here, we report the first evidence of a hexose transporter gene, Tbhxt1, in the
      ectomycorrhizal ascomycete Tuber borchii Vittadini. The protein encoded by Tbhxt1
      functionally complements the hxt-null mutant Saccharomyces cerevisiae EBYVW.4000.
      TBHXT1 has a strong preference for d-glucose (K(m)=38+/-10 microM) over d
      fructose (K(m)=16+/-5mM) and uncoupling experiments indicate that TBHXT1
      catalyzes the transport via a proton-symport mechanism. The investigations on the
      substrate specificity reveal that TBHXT1 also imports d-mannose, and the use of
      deoxyglucose analogues shows that the hydroxyl groups at C1, C3 and C4 are
      important for substrate recognition. Tbhxt1 is not regulated by fructose, but it
      reaches its highest level of expression at 3mM glucose and is repressed by very
      high glucose concentration. Prolonged carbon starvation condition upregulates
      Tbhxt1, while its expression remains at basal level in the ectomycorrhizal
      tissue. The mode of regulation of Tbhxt1 is consistent with its role as a high
      affinity d-glucose transporter.

PMID- 17005425
TI  - Acute angle-closure glaucoma precipitated by local tiotropium absorption.
AB  - Acute angle-closure glaucoma is a rare form of glaucoma occurring when the
      filtration mechanism for the aqueous humor is obstructed by apposition of the
      peripheral iris to the trabecular meshwork. It may be precipitated by pupillary
      dilatation in a predisposed eye. In this case report, a possible relationship
      between local tiotropium absorption and acute angle-closure glaucoma attack is
      presented.

PMID- 17005426
TI  - Heritability of plasma amino acid levels in different nutritional states.
AB  - Significant heritability has been shown for several plasma amino acid levels, but
      the results may have been confounded by sampling in a variety of nutritional
      states. We studied a group of families on a low protein steady-state diet in
      fasting and non-fasting states. Heritability of individual amino acids varied
      according to the nutritional state, suggesting the amount of genetic and
      environmental influences differ among the operative systems that control
      individual amino acid homeostasis throughout the feed/fast cycle.

PMID- 17005427
TI  - [Safety of blood transfusion at the international level. The role of WHO].
AB  - Blood safety is an international public health challenge, particularly since the
      emergence of HIV AIDS. Recognizing the gross disparities between countries in the
      adequacy of national blood supplies and the risks arising from poorly organized
      services, particularly in developing countries, the World Health Organization has
      developed a global strategy for blood safety and availability. Dr N. Dhingra,
      coordinator, blood transfusion safety, WHO Headquarters, and Dr V. Hafner, focal
      point for blood safety in the WHO regional office for Europe, present the main
      features of this strategy: well-organized, nationally coordinated blood
      transfusion services with quality systems in all areas; the collection of blood
      only from voluntary non-remunerated blood donors from low-risk populations; the
      quality-assured testing of all donated blood; the safe and appropriate use of
      blood and blood products; and global collaboration for blood safety. WHO's
      programs, some difficulties encountered and outcomes are also described in this
      article.

PMID- 17005428
TI  - [Preoperative treatment impact for ultralow rectal carcinoma sphincter
      preservation].
AB  - Sphincter preservation for low rectal carcinoma must be evaluated with a
      plurifactoriel approach. Multicentric randomised studies are unable to
      demonstrate a relationship between complete tumoral response and conservative
      sphincteric rate. Intersphincteric resection technique is becoming a main factor
      to transform conservative indication. Complete tumoral response should not be the
      only purpose of future trials.

PMID- 17005429
TI  - [Prophylactic cranial irradiation in non-small cell lung cancer].
AB  - Prophylactic cranial irradiation (PCI) has become part of the standard treatment
      in patients with small cell lung cancer (SCLC) in complete remission. Not only
      does it decrease the risk of brain recurrence by almost 50%, it has a significant
      positive effect on survival (5.4 percent increase at 3 years). As the prognosis
      of patients with locally advanced non-small cell lung cancer (NSCLC) has improved
      with combined modality treatment, brain metastases have also become an important
      cause of failure (10 to 30%, approaching 50% in certain studies as in SCLC).
      Survival after treatment of brain metastases is poor and impact on quality of
      life of patients is important. As in SCLC, 4 randomised evaluating PCI in NSCLC
      have been carried out in the seventies and early eighties. If 3 out of 4 trials
      have shown a significant decrease of brain metastases, none of them demonstrated
      any impact on survival. Thus PCI cannot be recommended as standard treatment in
      NSCLC, however new trials would be needed.

PMID- 17005430
TI  - [Clinical assessment of toxics deleterious to fertility].
AB  - This paper reviews the main toxics which are deleterious to fertility. Toxics are
      identified through in vitro, animal and clinical studies. The practitioner tries
      to assess whether a couple consulting for infertility has been exposed to such
      toxics. Some toxics are voluntarily taken: this is the case for tobacco, alcohol
      and other, maybe illegal, recreative drugs. Tobacco is the most frequently
      observed. The assessment of tobacco consumption and the implementation of weaning
      procedures have been studied in numerous papers: psychological, pharmacological
      and even immunotherapy-based approaches have been proposed. Alcohol abuse is even
      more difficult to assess: the border between acceptable convivial and excessive
      consumption is not clear-cut, except during pregnancy where there should be no
      alcohol consumption. This also holds for "recreative" drugs. It is usual clinical
      practice to register the medicine taken; some of these may be toxic for
      fertility. There is an ongoing work for listing these toxic drugs. Occupational
      life may also lead to exposure to toxics or be deleterious for fertility by
      imposing body constraints.

PMID- 17005431
TI  - [Procreative tourism as a last resort].

PMID- 17005432
TI  - Therapeutic effects of differentiated bone marrow stromal cell transplantation on
      rat models of Parkinson's disease.
AB  - This study was to explore curative effect of bone marrow stromal cells (BMSCs)
      differentiated into nestin-positive cells transplantation on rat Parkinson's
      disease (PD) model. The PD rats were selected and allocated randomly into three
      groups. BMSCs with differentiation, BMSCs without differentiation and
      physiological saline were injected into right striatum of PD rat. The rotation
      test and immunofluorescence double staining were done. Frequency of rotation was
      significantly less in differentiated or non-differentiated BMSCs groups than that
      in normal saline group. Brdu/GFAP- and Brdu/NSE-positive cells appeared except
      BrdU/TH-positive cells. BMSCs differentiated had better effect than that of BMSCs
      without differentiated and physiological saline group.

PMID- 17005433
TI  - Specific changes in the proteomic pattern produced by the BRCA1-Ser1841Asn
      missense mutation.
AB  - BRCA1 is a nuclear phosphoprotein that plays a key role in many cell functions,
      including DNA repair, control of transcription, recombination and cell cycle
      homeostasis. Inherited missense mutations in the BRCA1 gene may predispose to
      breast and ovarian cancer, but the molecular mechanisms underlying BRCA1-induced
      tumorigenesis are still to be elucidated. Functional studies performed so far
      have contributed to the characterization of several single-nucleotide variants,
      mostly located at the BRCT domain, but very little is known about modifications
      in the protein pattern occurring in cells carrying these mutations. To shed more
      light in the molecular events triggered by missense mutations affecting breast
      cancer susceptibility genes, we have analyzed the whole cell proteome of stably
      transfected HeLa cell lines bearing three distinct single aminoacid changes in
      the BRCA1 protein (Ser1841Asn, Met1775Arg and Trp1837Arg) by means of liquid
      chromatography coupled to tandem-mass spectrometry. The results show that the
      Met1775Arg and the Trp1837Arg do not produce significant changes in the proteomic
      pattern compared to cells transfected with the wild-type BRCA1 cDNA. On the other
      hand, a different profile is detected in the BRCA1 Ser1841Asn-bearing cell line.
      In this particular subset, our attention has been focused on two proteins--the
      tumor protein D52 (TD52) and the folate receptor alpha (FOL1)--whose expression
      has been already reported to be upregulated in breast cancer, as well as in other
      tumors. Our findings indicate that Ser1841Asn BRCA1 mutation is able to activate
      specific protein pathways that are not triggered by other single aminoacid
      changes and pinpoint to the role TD52 and FOL1 as potential markers in breast
      cancer patients carrying this particular BRCA1 gene alteration.

PMID- 17005434
TI  - NEDD1: function in microtubule nucleation, spindle assembly and beyond.
AB  - Nedd1 was originally identified as a developmentally regulated gene in the mouse
      central nervous system. NEDD1 has homologues across a range of species, being
      particularly conserved in a region of WD40 repeats contained in the amino
      terminal half of the protein. Human NEDD1 was recently found to localise to the
      centrosome and mitotic spindle. It binds to the components of the gamma-tubulin
      ring complex and target this complex to the centrosome and spindle. Depletion of
      NEDD1 causes loss of the gamma-tubulin ring complex from the centrosome and
      results in the failure of microtubule nucleation and spindle assembly. In
      addition, phosphorylation of NEDD1 during mitosis is critical for targeting gamma
      tubulin to the spindle, but not the centrosome. There is still much unknown about
      the function of this protein and how it may be involved in development and
      disease. This short review summarises some of the recent work on NEDD1 and
      discusses how this interesting protein may have additional yet unexplored
      functions.

PMID- 17005435
TI  - Bayesian associative learning.
AB  - The Bayesian approach to belief updating is par excellence a theory of learning-
      a theory of how beliefs should be revised in the light of new evidence. Yet
      despite its considerable utility as a framework for understanding cognition, it
      has not been prominent in theorizing about elementary learning processes in
      animals and humans. New research by Kruschke seems set to change this and to
      offer a bridge between rational and empirically descriptive accounts of learning.

PMID- 17005436
TI  - Multivalent interactions at interfaces.
AB  - Multivalency describes the interaction between multivalent receptors and
      multivalent ligands. It plays a pivotal role in biochemistry, particularly in
      protein-carbohydrate interactions, both in solution and at interfaces. At
      interfaces in particular, multivalency is often poorly understood in a
      quantitative sense. Research on multivalency is currently an interplay of the
      fields of biochemistry and supramolecular chemistry. On the one hand, the
      understanding of supramolecular interactions at interfaces provides a tool for
      the quantitative description of multivalency at interfaces. On the other hand,
      the multivalent design rules developed in biological chemistry are applied in
      novel supramolecular nanostructures. The current review focuses on the former
      perspective (i.e. the use of well defined supramolecular platforms that function
      as model systems for understanding multivalent phenomena at interfaces).

PMID- 17005437
TI  - Prognostic factors in head-and-neck cancer patients treated with surgery followed
      by intensity-modulated radiotherapy (IMRT), 3D-conformal radiotherapy, or
      conventional radiotherapy.
AB  - In 148 head-and-neck cancer patients treated with surgery plus radiotherapy (RT),
      IMRT, 3D-conformal RT, and conventional RT and 10 potential prognostic factors
      were evaluated for overall survival (OS), metastasis-free survival (MFS), and
      loco-regional control (LC). On univariate analysis, ECOG performance status, T
      stage, AJCC-stage, extent of resection, and pre-RT hemoglobin level (>or=12 g/dl
      better than <12 g/dl) were significantly associated with treatment outcome,
      whereas RT technique had no significant impact. On multivariate analysis,
      performance status maintained significance for OS (P=0.019), AJCC-stage for LC
      (P=0.034), extent of resection for OS (P=0.045) and MFS (P=0.021), pre-RT
      hemoglobin for MFS (P<0.001). IMRT was associated with less xerostomia than
      conformal RT and conventional RT (17% versus 63% and 73%, P=0.037). Otherwise,
      acute and late toxicity was similar. Outcome was significantly associated with
      performance status, tumor stage, extent of resection, and pre-RT hemoglobin. The
      three radiation techniques provided similar disease control. IMRT was effective
      in significantly reducing xerostomia.

PMID- 17005438
TI  - Professional delay in head and neck cancer patients: analysis of the diagnostic
      pathway.
AB  - The aim of this study was to identify which factors are related to specialist
      delay and to determine the length of the diagnostic pathway in head and neck
      cancer patients. Three hundred and six patients with a carcinoma of the larynx,
      pharynx or oral cavity were included in the study. Logistic regression analysis
      was used to identify risk factors for specialist delay. Large (T3-T4) tumors
      showed significantly less specialist delay than small (T1-T2) tumors (p=0.045,
      odds ratio [OR]=0.6). Pharyngeal (p=0.00, OR=0.2) and oral carcinomas (p=0.00,
      OR=0.2) had less specialist delay than glottic carcinomas. Hoarseness was
      associated with prolonged specialist delay (p=0.00, OR=5.9). Heavy drinking in
      combination with smoking (p=0.005, OR=0.3), a sore throat (p=0.02, OR=0.4) or
      having a lesion (p=0.03, OR=0.2) showed a shorter diagnostic period. The duration
      of the diagnostic process in a general hospital ranged from 0 to 570 days, with a
      median of 14 days. Only a small group of patients met the ideal management
      standards in our head and neck clinic. Although prolonged delay was associated
      with small (glottic) tumors, the diagnostic process takes a fairly long time. The
      results indicate that continued educational programs for professionals are
      warranted.

PMID- 17005439
TI  - Amplifications of TAOS1 and EMS1 genes in oral carcinogenesis: association with
      clinicopathological features.
AB  - Amplification of chromosomal region 11q13 is one of the genetic alterations most
      frequently observed in oral squamous cell carcinoma (OSCC). Both TAOS1, a
      recently identified gene, and EMS1 were thought as two important target oncogenes
      for driving 11q13 amplification, and their contributions to oral carcinogenesis
      were hypothesized. Therefore we investigated amplifications of TAOS1 and EMS1
      genes and their relations to clinicopathological variables in premalignant
      lesions (leukoplakias) and primary OSCC. TAOS1 amplification, beginning from mild
      dysplastic epithelia, occurred in 33.3% of leukoplakias and 51.5% of OSCC. EMS1
      amplification, beginning from moderate-dysplastic epithelia, occurred in 20% of
      leukoplakias and 57.6% of OSCC. Both gene amplifications were significantly
      related to different stages of oral carcinogenesis (p<0.05). During multistage
      carcinogenesis, no gene amplification was observed in normal tissue and non
      dysplastic leukoplakias while, in OSCC with metastasis, amplification frequency
      increased significantly (p<0.005). Both TAOS1 and EMS1 amplifications were
      significantly associated with larger tumor size, presence of lymph node
      metastasis, poor histological differentiation and advanced clinical stage. Our
      data suggested potential roles in oral carcinogenesis and that TAOS1 might be
      involved earlier than EMS1. Both genes might be candidate biomarkers for
      diagnosis and prognosis in OSCC.

PMID- 17005440
TI  - F-box proteins everywhere.
AB  - The ubiquitin proteasome system is a key regulator of many biological processes
      in all eukaryotes. This mechanism employs several types of enzymes, the most
      important of which are the ubiquitin E3 ligases that catalyse the attachment of
      polyubiquitin chains to target proteins for their subsequent degradation by the
      26S proteasome. Among the E3 families, the SCF is the best understood; it
      consists of a multi-protein complex in which the F-box protein plays a crucial
      role by recruiting the target substrate. Strikingly, nearly 700 F-box proteins
      have been predicted in Arabidopsis, suggesting that plants have the capacity to
      assemble a multitude of SCF complexes, possibly controlling the stability of
      hundreds of substrates involved in a plethora of biological processes.
      Interestingly, viruses and even pathogenic bacteria have also found ways to
      hijack the plant SCF and to reprogram it for their own purposes.

PMID- 17005441
TI  - Genotoxicity of five food preservatives tested on root tips of Allium cepa L.
AB  - The effects of the food preservatives sodium benzoate (SB), boric acid (BA),
      citric acid (CA), potassium citrate (PC) and sodium citrate (SC) have been
      studied on root tips of Allium cepa L. Roots of A. cepa were treated with a
      series of concentrations, ranging from 20 to 100 ppm for 5, 10 and 20 h. The
      results indicate that these food preservatives reduced mitotic division in A.
      cepa compared with the respective control. Mitotic index values were generally
      decreased with increasing concentrations and longer treatment times.
      Additionally, variations in the percentage of mitotic stages were observed. The
      total percentage of aberrations generally increased with increasing
      concentrations of these chemicals and the longer period of treatment. Different
      abnormal mitotic figures were observed in all mitotic phases. Among these
      abnormalities were anaphase bridges, C-mitosis, micronuclei, lagging, stickiness,
      breaks and unequal distribution.

PMID- 17005442
TI  - Investigation of the interaction between curcumin and nucleic acids in the
      presence of CTAB.
AB  - It is found that nucleic acid can enhance the resonance light scattering (RLS)
      enhancement effect of curcumin (CU) in the presence of cationic surfactant
      cetyltrimethylammonium bromide (CTAB). The investigation indicates that in BR (pH
      4.3) buffer, both the positive CTAB and negative yeast RNA (yRNA) combine and
      form a positive large association, then which is bound on the two carbon atoms of
      the carbonyls of CU through hydrogen bond and hydrophobic force and form CU-CTAB
      yRNA ternary complex, resulting in the RLS enhancement of this system. Based on
      it, a sensitive method for determination of nucleic acids at ngml(-1) is
      established.

PMID- 17005443
TI  - Photoinduced intermolecular electron transfer process of fullerene (C60) and
      amine-substituted fluorenes studied by laser flash photolysis.
AB  - Photoinduced intermolecular electron transfer process of fullerene (C60) with 9,9
      bis(4-triphenylamino)fluorene (BTAF) and 9,9-dimethoxyethyl-2
      diphenylaminofluorene (DAF) in toluene and benzonitrile has been investigated by
      nanosecond laser photolysis technique in the visible/near-IR regions. By the
      selective excitation of C60 using 532 laser light, it has been proved that the
      electron transfer takes place from the ground states BTAF and DAF to the triplet
      excited state of C60 ((3)C60*) by observing the radical anion of C60 and radical
      cation of BTAF and DAF. It was observed that the electron transfer of
      BTAF/(3)C60* is more efficient than DAF/(3)C60* reflecting the effect of amine
      substitutents of the fluorene moiety on the efficiency of the electron transfer
      process. On addition of a viologen dication (OV(2+)), the electron of the anion
      radical of C60 mediates to OV(2+) yielding the OV(+). These results proved that
      the photosensitized electron-transfer/electron-mediating processes have been
      confirmed by the transient absorption spectral method.

PMID- 17005445
TI  - Stable coreceptor usage of HIV in patients with ongoing treatment failure on
      HAART.
AB  - BACKGROUND: Disease progression in HIV infection has been associated with switch
      of viral coreceptor usage from CCR5 to CXCR4. OBJECTIVES: To investigate the
      relationship between HIV-coreceptor tropism and clinical and virological outcome
      in 40 heavily pretreated patients over time. METHODS: Coreceptor phenotype was
      predicted after sequencing the V3 loop of the HIV glycoprotein 120. RESULTS:
      Coreceptor use was stable during observation time in 87% of patients, and CCR5
      tropism was predominant. Viral mutations in the pol gene and clinical parameters
      were not predictive for coreceptor switching. CONCLUSIONS: Even in patients with
      repeated HAART failure, CCR5 antagonists might be a valuable treatment option.

PMID- 17005444
TI  - Human herpesvirus-6B active infection associated with relapsing bilateral
      anterior optic neuritis.
AB  - BACKGROUND AND OBJECTIVES: Human herpesvirus-6 (HHV-6) is the causative agent of
      exanthem subitum. Both HHV-6 variants, A and B, have been associated with central
      nervous system (CNS) diseases, suggesting a wide neuropathogenic potential. We
      describe a case of recurrent bilateral anterior optic neuritis with HHV-6 active
      infection associated with clinical relapses. CASE REPORT: A 23-year old woman
      presented with progressive visual impairment, bilateral papillitis and painful
      ocular movements. Nested polymerase chain reaction (PCR) for DNA viruses, HHV-6
      variant specific real time quantitative PCR, serological analysis and
      retrotranscription PCR (RT-PCR) for HHV-6 mRNA transcripts were performed. Nested
      PCR in PBMC and CSF samples was negative for all viruses but positive for HHV-6
      DNA, subtyped as HHV-6B. The disease had a relapsing/remitting course. During
      relapses PBMC samples remained positive for HHV-6 DNA, and HHV-6 active infection
      was confirmed by the presence of anti-HHV-6 IgM and of HHV-6 U27 mRNA transcript.
      High viremia levels and relapses were overlapping. After the last relapse, the
      patient was successfully treated with gancyclovir. CONCLUSIONS: The case reported
      here suggests a possible association of HHV-6 in bilateral optic neuritis. HHV-6
      could be monitored when bilateral optic neuritis is identified, in order to
      establish an appropriate antiviral therapy.

PMID- 17005447
TI  - Effects of thirty-minute mobile phone use on visuo-motor reaction time.
AB  - OBJECTIVE: To investigate whether exposure to pulsed high-frequency
      electromagnetic field (pulsed EMF) emitted by a mobile phone has short-term
      effects on the visuo-motor choice reaction time (RT) and movement time (MT).
      METHODS: A double blind, counterbalanced crossover design was employed. In 16
      normal subjects, we studied the performance of a visuo-motor precued choice
      reaction time task (PCRT) before and after exposure to EMF emitted by a mobile
      phone for 30 minutes or sham exposure. RESULTS: The RTs and MTs under different
      conditions of precue information were not affected by exposure to pulsed EMF
      emitted by a mobile phone or by sham phone use. CONCLUSIONS: Thirty minutes of
      mobile phone use has no significant short-term effect on the cortical visuo-motor
      processing as studied by the present PCRT task. SIGNIFICANCE: This is the first
      study to investigate visuo-motor behavior in relation to mobile phone exposure.
      No significant effect of mobile phone use was demonstrated on the performance of
      the visuo-motor reaction time task.

PMID- 17005446
TI  - Spatio-temporal patient-individual assessment of synchronization changes for
      epileptic seizure prediction.
AB  - OBJECTIVE: Abnormal synchronization of neurons plays a central role for the
      generation of epileptic seizures. Therefore, multivariate time series analysis
      techniques investigating relationships between the dynamics of different neural
      populations may offer advantages in predicting epileptic seizures. METHODS: We
      applied a phase and a lag synchronization measure to a selected subset of
      multicontact intracranial EEG recordings and assessed changes in synchronization
      with respect to seizure prediction. RESULTS: Patient individual results, group
      results, spatial aspects using focal and extra-focal electrode contacts as well
      as two evaluation schemes analyzing decreases and increases in synchronization
      were examined. Averaged sensitivity values of 60% are observed for a false
      prediction rate of 0.15 false predictions per hour, a seizure occurrence period
      of half an hour, and a prediction horizon of 10 min. For approximately half of
      all 21 patients, a statistically significant prediction performance is observed
      for at least one synchronization measure and evaluation scheme. CONCLUSIONS: The
      results indicate that synchronization changes in the EEG dynamics preceding
      seizures can be used for seizure prediction. Nevertheless, the underlying
      pathogenic mechanisms differ and both decreases and increases in synchronization
      may precede epileptic seizures depending on the structures investigated.
      SIGNIFICANCE: The prediction method, optimized values of intervention times, as
      well as preferred brain structures for the EEG recordings have to be determined
      for each patient individually offering the chance of a better patient-individual
      prediction performance.

PMID- 17005448
TI  - Stimulus context determines whether non-target stimuli are processed as task
      relevant or distractor information.
AB  - OBJECTIVE: The P300 event-related brain potential (ERP) was elicited using a
      visual three-stimulus oddball paradigm (standard 0.70, target 0.15, non-target
      0.15) to examine how target/standard stimulus context affects non-target
      processing. METHODS: Target/standard discrimination difficulty (easy or
      difficult) and non-target /target similarity (similar or dissimilar) were
      manipulated orthogonally. Participants (N=13) were instructed to respond to each
      infrequent target stimulus by pressing a button. RESULTS: Target stimuli in all
      task conditions elicited P3b, which was affected only by the difficulty of
      target/standard discrimination. When target/standard discrimination was easy, the
      amplitude of non-target P3 was larger for similar than for dissimilar non-target.
      In contrast, when target/standard discrimination was difficult, non-target
      stimuli elicited P3a, the amplitude of which was larger for dissimilar than for
      similar non-target. Thus, the P300 component for non-target stimuli and the
      pattern of the effect of target similarity on each P300 component varied as a
      function of the target/standard stimulus context. CONCLUSIONS: The
      target/standard stimulus context influences the attentional set for stimulus
      processing such that it determines whether non-target stimuli are processed as
      task-relevant or distractor information. SIGNIFICANCE: The present results are
      important for understanding the mechanism of cognitive modification in non-target
      processing.

PMID- 17005450
TI  - Characterization of a Mycobacterium tuberculosis mutant deficient in pH-sensing
      adenylate cyclase Rv1264.
AB  - Mycobacterium tuberculosis open reading frame Rv1264 encodes an adenylate cyclase
      that exhibits its highest enzymatic activity at an acidic pH of 6.0. This is the
      pH M. tuberculosis encounters in the phagosome. Consequently Rv1264 has been
      suggested to sense the phagosomal milieu resulting in adaption of M. tuberculosis
      to its intracellular niche. A targeted knock-out mutant deficient in Rv1264,
      however, exhibits wild-type virulence.

PMID- 17005452
TI  - The 3rd Judith Hoyer Lecture in epilepsy, December 2, 2005 opening remarks.
AB  - On December 2, 2005, Dr. Jeffrey L. Noebels presented the third lecture in a
      series highlighting the promise of epilepsy research. Opening remarks were
      provided by Dr. Story C. Landis, Director of the National Institute of
      Neurological Disorders and Stroke, and by Representative Steny Hoyer (D-MD). The
      lecture series is held in memory of Mrs. Judith Hoyer, an active member of the
      Board of Directors of the Epilepsy Foundation (EF) and the late wife of Rep.
      Hoyer. Mrs. Hoyer spent her life both helping families to cope with epilepsy and
      promoting research into a cure and a better quality of life for those with the
      disorder. The purpose of the lecture is to raise awareness of epilepsy among
      researchers and the public and provide intellectual stimulation that will
      encourage continuing progress toward finding a cure for epilepsy.

PMID- 17005451
TI  - Tick control: further thoughts on a research agenda.
AB  - Tick control is a subject that has stimulated intense interest for more than a
      century. This article is a commentary on the research needs for tick control
      proposed in Peter Willadsen's recent article and it calls attention to tick
      control strategies that were either poorly represented or omitted from the
      latter. Special consideration is given to host-targeted devices to control
      disease vector ticks infesting wildlife, to pheromone-impregnated decoys for
      attracting and killing ticks in the natural environment and on hosts, and to more
      up-to-date advances in vaccine development.

PMID- 17005453
TI  - Role of the endothelium in pulmonary arterial hypertension.
AB  - Pulmonary hypertension represents a significant disease burden in both the
      developed and developing worlds. Certain forms of pulmonary hypertension are more
      common in some countries than others but people of all races, all ages and both
      sexes are affected. Treatment options are limited and expensive. The development
      of new therapies will be determined by improved understanding of endothelial cell
      biology.

PMID- 17005454
TI  - Role of sympathetic nerves on early embryonic development and immune modulation
      of uterus in pregnant mice.
AB  - To determine the role of sympathetic nerves in the early embryonic development
      and the immune modulation of maternal uterus during pregnancy, a model of
      chemical sympathectomy in mice was established by intraperitoneal injection of 6
      hydroxydopamine (6-OHDA). The embryonic development and the distribution of
      maternal uterine immunocytes were investigated during early pregnancy (E1-E9)
      with methods of histology, immunohistochemistry and ELISA. Our data showed that
      in the 6-OHDA-treated group, the number of implanted embryos was only 64.4% of
      that in the control group at E7, and the development of uterine glands and
      vessels was poor in pregnant mice. In addition, in uterine tissues of 6-OHDA
      treated mice, the number of CD8+ T cells increased ten-fold and the concentration
      of IL-2 increased 3.6-fold at E5. However, no obvious changes to the number of
      CD4+ T cells and IL-4 were observed. Thus, the CD4+/CD8+ T cells ratio
      significantly decreased, while the IL-2/IL-4 ratio significantly increased. These
      findings indicated that the activation of sympathetic nerves might be favorable
      to fetal survival and development during early pregnancy through influencing on
      immune function and decidua formation of uterus.

PMID- 17005455
TI  - Mechanical effects of genioglossus muscle stimulation on the pharyngeal airway by
      MRI in cats.
AB  - To examine the regional mechanical effects of selective genioglossus muscle
      activation on pharyngeal airway size and function, magnetic resonance images of
      the pharyngeal airway were obtained in five paralyzed, anesthetized cats over a
      range of positive and negative pressures in an isolated, sealed upper airway.
      When all results across pressure levels and pharyngeal regions were analyzed,
      genioglossus stimulation significantly increased the cross-sectional area (CSA)
      of the nasopharyngeal airway. Within specific regions, stimulation tended toward
      significantly increasing cross-sectional airway area in the mid-nasopharynx.
      Despite its dilating effect, genioglossus muscle stimulation did not alter
      compliance in the nasopharyngeal airway, as evidenced by the similar slopes of
      the pressure versus cross-sectional area relationships with and without
      stimulation. Finally, airway shape in the mid pharynx became more circular with
      either increased airway pressure or genioglossus stimulation. The results
      indicate that selective stimulation of the genioglossus muscle dilates the
      nasopharynx and provide evidence that stimulation of the genioglossus alone does
      not alter airway compliance.

PMID- 17005456
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      for the determination of BPR0L075, a novel antimicrotuble agent, in rat plasma:
      application to a pharmacokinetic study.
AB  - A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC
      MS/MS) had been developed and validated to determine the concentrations of
      BPR0L075 in rat plasma. After a simple protein precipitation of plasma samples by
      acetonitrile, BPR0L075 was analyzed on a C(8) column at a flow rate of 0.5
      mL/min. The mobile phase consisted of a mixture of 10 mM ammonium acetate
      containing 0.1% formic acid and acetonitrile (20:80, v/v). Both BPR0L075
      (analyte) and the internal standard (BPR0L092) were determined using electro
      spray ionization and the MS data acquisition was via multiple reactions
      monitoring (MRM) in positive scanning model. The MS/MS ion transitions monitored
      are m/z 342.2/195.2 and 312.5/165.2 for BPR0L075 and BPR0L092, respectively. The
      low limit of quantitation was 0.5 ng/mL. Each plasma sample was chromatographed
      within 5 min. The method was validated with respect to linearity, accuracy,
      precision, recovery, and stability. A good linear relationship was observed over
      the concentration range of 0.5-1000 ng/mL (r>0.9994). Absolute recoveries ranged
      from 63.45 to 68.34% in plasma at the concentrations of 2, 40, 400, and 800
      ng/mL. The intra- and inter-day accuracy ranged from 92.04 to 111.80%. Intra- and
      inter-day relative standard deviations were 1.08-3.29% and 1.96-5.46%,
      respectively. This developed and validated assay method had been successfully
      applied to a pharmacokinetic study after intravenous injection of BPR0L075 in
      rats at a dose of 5mg/kg.

PMID- 17005457
TI  - Inhibition of glutaminyl cyclase alters pyroglutamate formation in mammalian
      cells.
AB  - Mammalian cell lines were examined concerning their Glutaminyl Cyclase (QC)
      activity using a HPLC method. The enzyme activity was suppressed by a QC specific
      inhibitor in all homogenates. Aim of the study was to prove whether inhibition of
      QC modifies the posttranslational maturation of N-glutamine and N-glutamate
      peptide substrates. Therefore, the impact of QC-inhibition on amino-terminal
      pyroglutamate (pGlu) formation of the modified amyloid peptides Abeta(N3E-42) and
      Abeta(N3Q-42) was investigated. These amyloid-beta peptides were expressed as
      fusion proteins with either the pre-pro sequence of TRH, to be released by a
      prohormone convertase, or as engineered amyloid precursor protein for subsequent
      liberation of Abeta(N3Q-42) after beta- and gamma-secretase cleavage during
      posttranslational processing. Inhibition of QC leads in both expression systems
      to significantly reduced pGlu-formation of differently processed Abeta-peptides.
      This reveals the importance of QC-activity during cellular maturation of pGlu
      containing peptides. Thus, QC-inhibition should impact bioactivity, stability or
      even toxicity of pyroglutamyl peptides preventing glutamine and glutamate
      cyclization.

PMID- 17005458
TI  - Improved survival of patients presenting with acute variceal bleeding. Prognostic
      indicators of short- and long-term mortality.
AB  - BACKGROUND AND AIM: Variceal bleeding is a severe complication of portal
      hypertension with a mortality rate between 30% and 60% in previous studies.
      During the last two decades the treatment of these patients has been improved.
      The aim of this study was to investigate the clinical outcome of patients after
      an episode of acute variceal bleeding and to identify risk factors for early and
      late mortality in these patients. MATERIALS AND METHODS: All patients with acute
      variceal bleeding hospitalised at two large hospitals between January 1, 1999 and
      June 30, 2004, were retrospectively enrolled in this study. After discharge,
      patients were followed until death or study closure date, on June 30, 2005.
      Bleeding related mortality, 6-week, 1-year and overall mortality were evaluated
      as well as factors related to early and late mortality. RESULTS: One hundred and
      forty one patients were included (114 men, 27 women) with a mean age of 60.5+/
      13.5 years. In hospital, 6-week, 1-year and overall mortality were 12.1%, 18.4%,
      32.6% and 48.2%, respectively. The mean length of hospitalisation was 11.4+/-9
      days (1-55) and the mean packed red blood cell requirement was 3.9+/-3.7 (0-25).
      The rate of recurrent bleeding was 10.7% during initial hospitalisation. Being
      Child-Pugh C (p=0.003) and shock on admission (p=0.037) were independent
      predictors of 6-week mortality, while being Child-Pugh C (p=0.028), presence of
      hepatocellular carcinoma or other neoplasia (p=0.04) and partial thromboplastin
      time (p=0.021) during the initial admission were independent predictors for 1
      year mortality. Mortality was not affected by the presence of active bleeding
      and/or white nipple at emergency endoscopy. Also presence of infection was not an
      adverse factor of clinical outcome in our patients. CONCLUSIONS: In conclusion,
      the clinical outcome of patients with acute variceal bleeding is better in
      comparison with previous studies. The severity of liver failure as well as the
      presence of neoplasia mainly affects the survival.

PMID- 17005459
TI  - Progression from iron deficiency anaemia to cobalamin depletion in autoimmune
      atrophic gastritis: is it simply a question of time?

PMID- 17005462
TI  - The procedures for assessing oncological research in Spain.

PMID- 17005463
TI  - Cancer and modernity.

PMID- 17005464
TI  - Symptom management, supportive and palliative care: the continuum of care in the
      cancer patient. The SEOM's continuing care section.

PMID- 17005465
TI  - Molecular biology of malignant gliomas.
AB  - Gliomas are the most common primary brain tumours. In keeping with the degree of
      aggressiveness, gliomas are divided into four grades, with different biological
      behaviour. Furthermore, as different gliomas share a predominant histological
      appearance, the final classification includes both, histological features and
      degree of malignancy. For example, gliomas of astrocytic origin (astrocytomas)
      are classified into pilocytic astrocytoma (grade I), astrocytoma (grade II),
      anaplastic astrocytoma (grade III) and glioblastoma multiforme (GMB) (grade IV).
      Tumors derived from oligodendrocytes include grade II (oliogodendrogliomas) and
      grade III neoplasms (oligoastrocytoma). Each subtype has a specific prognosis
      that dictates the clinical management. In this regard, a patient diagnosed with
      an oligodendroglioma totally removed has 10-15 years of potential survival. On
      the opposite site, patients carrying a glioblastoma multiforme usually die within
      the first year after the diagnosis is made. Therefore, different approaches are
      needed in each case. Obviously, prognosis and biological behaviour of malignant
      gliomas are closely related and supported by the different molecular background
      that possesses each type of glioma. Furthermore, the ability that allows several
      low-grade gliomas to progress into more aggressive tumors has allowed cancer
      researchers to elucidate several pathways implicated in molecular biology of
      these devastating tumors. In this review, we describe classical pathways involved
      in human malignant gliomas with special focus with recent advances, such as
      glioma stem-like cells and expression patterns from microarray studies.

PMID- 17005466
TI  - DNA repair inhibitors in cancer treatment.
AB  - Chemotherapy and radiation are two important modalities for cancer treatment.
      Many agents in clinical used have the ability to induce DNA damage, however they
      may be highly cytotoxic as a secondary effect. Different mechanisms are involved
      both, in detection and repair of DNA damage. The modulation of these pathways,
      has a great impact on clinical outcome and is frequently responsible of
      therapeutic resistance. Therefore, pharmacological inhibition of DNA damage
      repair pathways has been explored as a useful strategy to enhance chemo and
      radiosensitivity, thus it could be used for reversing drug resistance. Different
      agents have shown excellent results in preclinical studies in combination with
      radiation or chemotherapy. Early phase clinical trials are now being carried out
      using different DNA repair inhibitors targeting several enzymes such as PARP, DNA
      PK or MGMT.

PMID- 17005469
TI  - Conservative treatment for infiltrating breast cancer. Ten years follow-up
      experience.
AB  - INTRODUCTION: We retrospectively analyze our experience in conservative treatment
      for infiltrating advanced breast cancer before implementation of selective
      sentinel node biopsy, specially focusing on characteristics, incidence, treatment
      and evolution of local-regional recurrences, disease-free survival time, overall
      survival and patient's satisfaction. MATERIAL AND METHODS: From January 1984 to
      31st December 1998, 739 female patients were operated in our institution,
      diagnosed as having infiltrating breast cancer. One hundred and eighty-eight
      patients (25.43%) received conservative treatment and they were followed up until
      December 2003. RESULTS: Average age when diagnosed was 50.42 years old (24-87
      years). 53.19% of the patients were premenopausal. After a median follow-up of
      129 months (60-198 months), 13 women (6.91%) presented local -regional recurrence
      and the disease-free time was 48.4 months (8-108 months). Global survival rate
      was 83.5% and disease free survival rate was 80.85%. CONCLUSIONS: The management
      of choice for early stage (I and II) infiltrating breast cancer is nowadays
      conservative, with a low local-regional recurrence rate and survival rate that
      are comparable to radical mastectomy, according to the literature. It's a safe
      and efficient method that let us preserve the breast with a good esthetical
      result. In selected cases, when a regional recurrence occurs, a second
      conservative management is possible with a good control of the disease, although
      the most widely accepted treatment in these cases is total mastectomy.

PMID- 17005468
TI  - Quality of Life assessment through the EORTC questionnaires of colorectal cancer
      patients in advanced disease stages.
AB  - PURPOSE: The purpose of the present work is to evaluate Quality of Life in a
      group of colorectal cancer patients in advanced stages of their disease, along a
      standard chemotherapy treatment protocol, through the EORTC core questionnaire
      QLQ-C30 and the colorectal cancer module QLQ-CR38. These two questionnaires had
      previously been validated in our country. The present study has the novelty of
      its use during the chemotherapy treatment. MATERIALS AND METHODS: A consecutive
      sample of 44 colon o rectal cancer patients in stage IV, from an initial group of
      46 patients who were addressed, have filled in the questionnaires, in three
      moments during their treatment process. Clinical and demographic data have also
      been recorded. Quality of Life scores and changes in them among the three
      assessments have been calculated. RESULTS: The quality of life scores of patients
      who have followed the treatment have been >70 points (100) in most dimensions,
      and has shown similar to the clinical data. Changes of >20 points in the quality
      of life scores during the treatment process appear in areas related to toxicity,
      fatigue and insomnia. Quality of life has been stable or has had small changes
      (between 10 and 20 points) in most dimensions. CONCLUSIONS: Quality of Life in
      the present sample has been good in general. The treatment has been administered
      to patients who could tolerate it adequately.

PMID- 17005470
TI  - Significance of the immunohistochemical detection of lymph node micrometastases
      in stage II colorectal carcinoma.
AB  - BACKGROUND: Survival results of stage II colorectal cancer patients have led to
      major efforts to identify the subset of patients at risk for disease relapse and
      adjuvant therapies benefit. Immunohistochemistry is being explored to detect
      undetectable microscopic lymph node micrometastases. MATERIAL AND METHODS: A
      retrospective analysis of a 105 consecutive stage II colorectal cancer patients
      was performed. Two four-micres sections were obtained from each lymph node. These
      slides were stained with AE1-AE3 monoclonal antibodies against cytoskeleton using
      DAKO EnVision visualization system. Micrometastases were identified either as
      isolated cells or as well-defined glandular cell clusters with cytoplasm but not
      the nucleus stained with cytoskeleton antibodies. RESULTS: 665 lymph nodes
      isolated from 105 patients were analyzed. Lymph nodes micrometastases were
      assessed in 26 out of the 105 patients. 42 (6.3%) out of 665 lymph nodes were
      infiltrated. Most of these metastases consisted of isolated cell cluster
      localized in marginal and interfollicular sinus of lymph nodes. The relapse rate
      was 23.1% among the patients with immunohistochemical detected lymph node
      micrometastes and 20.3% for the patients without lymph node involvement. This
      result lacked statistical significance (p = 0.759). DISCUSSION: AE1/AE3 lymph
      node immunohistochemical staining in stage II colorectal cancer is an interesting
      biological phenomenon but it fails to identify patients at higher risk of relapse
      who deserve a more aggressive adjuvant attitude.

PMID- 17005471
TI  - Testicular neoplasms. Evaluation of the experience during 25 years in a military
      hospital.
AB  - INTRODUCTION: Testicular tumors are frequent in young adults, coinciding with
      incorporation to military service. The present study evaluates the tumor
      characteristics, time course and results obtained with the treatments used in our
      center for this type of neoplasms. MATERIAL AND METHODS: A retrospective
      longitudinal study was conducted in a cohort of 98 patients with an average age
      of 28.6 years, subjected to orchiectomy for testicular tumors in our center
      between 1979 and 2004. Data were collected relating to patient age, tumor
      characteristics, the outcome of treatment, and the course of the disease.
      RESULTS: The right testicle was affected in 61% (with significant differences
      versus the left side). The most common histological type corresponded to non
      seminomatous germ cell tumors (NSGCTs) (65.3%), followed by pure seminomas
      (27.6%) and non-germinal cell tumors (NGCs) (7.1%). NSGCT was diagnosed at a
      significantly younger average age (23.2 years) than the other two tumor types.
      Stage I was the most frequent presentation (58%). Seminomas presented in stage I
      significantly more often (80%) than the others tumors. The data collected over
      the 25-year study period showed no significant variations in tumor
      characteristics. The log-rank test showed a significant difference in terms of
      patient survival according to the tumor cell line (p = 0.000) and stage (p =
      0.000), except between stages I and II, where no significant differences were
      observed in terms of survival. CONCLUSIONS: Non-seminomatous germ cell tumors
      (NSGCTs) are the most frequent testicular tumors in young adults. Most neoplasms
      are diagnosed in early stages, the prognosis being better in the case of
      seminomas and tumor stages I and II.

PMID- 17005472
TI  - Radiofrequency ablation for hepatocellular carcinoma and liver metastases:
      experience in Hospital La Paz.
AB  - INTRODUCTION: Radiofrequency ablation for patients presenting with non-resectable
      primary or metastatic liver tumours seems to be a valid therapeutic alternative.
      In the present study, we show a descriptive list of indications, results and
      complications of Radiofrequency Ablation Technique for treating non-resectable
      solid hepatic tumours. MATERIALS AND METHODS: Twenty two patients were included
      in this study; eleven of them (50%) sustained liver metastases from colorectal
      adenocarcinoma, ten patients (45.5%) had hepatocellular carcinoma and 1 patient
      had insulinoma. RESULTS: Local recurrence rate of hepatocellular carcinoma was
      22.7% and 27.3% for colorectal carcinoma, after a respective median follow-up of
      21 and 14 months. Complications rate was 6.9% and technique-associated mortality
      rate was 0%. CONCLUSIONS: Radiofrequency ablation is an easy to make, safe and
      useful technique for the treatment of primary and metastatic liver tumours.

PMID- 17005473
TI  - Cutaneous nodes in a patient with advanced papillary carcinoma of the thyroid.
AB  - Cutaneous metastasis from thyroid carcinoma is infrequent. Leukemia as a second
      malignancy after treatment of thyroid cancer is also rare. We present a patient
      with a relapsed thyroid carcinoma treated with thyroid ablation with I 131 and
      loco-regional radiotherapy, who consulted by global worsening, weight lost, and
      multiple cutaneous nodes. Our patient is unusual in that she showed multisystem
      involvement at the time of hospital admission, and the specific skin lesions were
      the first sign of her acute monocytic leukemia.

PMID- 17005467
TI  - Somatic stem cells and the origin of cancer.
AB  - Most human cancers derive from a single cell targeted by genetic and epigenetic
      alterations that initiate malignant transformation. Progressively, these early
      cancer cells give rise to different generations of daughter cells that accumulate
      additional mutations, acting in concert to drive the full neoplastic phenotype.
      As we have currently deciphered many of the gene pathways disrupted in cancer,
      our knowledge about the nature of the normal cells susceptible to transformation
      upon mutation has remained more elusive. Adult stem cells are those that show
      long-term replicative potential, together with the capacities of self-renewal and
      multi-lineage differentiation. These stem cell properties are tightly regulated
      in normal development, yet their alteration may be a critical issue for
      tumorigenesis. This concept has arisen from the striking degree of similarity
      noted between somatic stem cells and cancer cells, including the fundamental
      abilities to self-renew and differentiate. Given these shared attributes, it has
      been proposed that cancers are caused by transforming mutations occurring in
      tissue-specific stem cells. This hypothesis has been functionally supported by
      the observation that among all cancer cells within a particular tumor, only a
      minute cell fraction has the exclusive potential to regenerate the entire tumor
      cell population; these cells with stem-like properties have been termed cancer
      stem cells. Cancer stem cells can originate from mutation in normal somatic stem
      cells that deregulate their physiological programs. Alternatively, mutations may
      target more committed progenitor cells or even mature cells, which become
      reprogrammed to acquire stem-like functions. In any case, mutated genes should
      promote expansion of stem/progenitor cells, thus increasing their predisposition
      to cancer development by expanding self-renewal and pluripotency over their
      normal tendency towards relative quiescency and proper differentiation.

PMID- 17005474
TI  - Recurrent pericardial effusion as initial manifestation of primary diffuse
      pericardial malignant mesothelioma.
AB  - The case of a 61-year-old woman who presented a recurrent symptomatic pericardial
      effusion and a malignant cardiac tamponade six months prior to the detection of a
      mediastinal anterior mass is described. Diffuse malignant pericardial
      mesothelioma was diagnosed after mediastinal mass biopsy. The patient underwent
      further oncological evaluation followed by chemotherapy.

PMID- 17005475
TI  - Total remission of thymus carcinoma after treatment with intravenous
      immunoglobulin.
AB  - We report the case of a 42 year-old woman with myasthenia gravis associated with
      a malignant thymoma. Despite surgery, chemotherapy and radiotherapy, the thymoma
      showed soft tissues, pleural and mediastinic progression. Unexpectedly, a
      complete remission of the thymoma was confirmed by FDG-PET after four cycles of
      immunoglobulins, administered as treatment for a myasthenic crisis. To our
      knowledge this is the first case report of complete remission of a malignant
      thymoma with immunoglobulin therapy.

PMID- 17005478
TI  - Advancing rehabilitation research: an interactionist perspective to guide
      question and design.
AB  - The purpose of this position statement is to propose an interactionist framework
      to bring together the existing literature and provide a unifying direction for
      rehabilitation research. The framework comprises three components: the conceptual
      model, the research question, and the research design. The interactionist
      conceptual model has been adapted from the World Health Organization
      International Classification of Functioning, Disability, and Health. The model
      forms the starting point that guides the specification of the research question,
      which, in turn, guides the selection of research design. This approach demands
      that the question takes precedence and that there be an extensive repertoire of
      research designs, each of which is valued for its 'goodness-of-fit' with the
      question, rather than an a priori, single hierarchical ordering of designs.
      Research designs must be appropriate for questions that examine the disability
      experience, development over the lifespan, multifaceted interventions, low
      incidence conditions, and development of new interventions. Analytical challenges
      include dealing with confounding, mediating, and moderating variables.
      Rehabilitation researchers--and those who fund their work--should consider and
      value the use of diverse research methods to best answer the questions posed from
      the interactionist perspective.

PMID- 17005479
TI  - Young women with fibromyalgia in the United States and Sweden: perceived
      difficulties during the first year after diagnosis.
AB  - PURPOSE: The major symptoms of fibromyalgia (FM)--pain, tiredness, disrupted
      sleep, and muscle weakness--severely impact everyday activities, including the
      paid work role of women who have had FM for a long time. There are no prospective
      studies on young and newly diagnosed women with FM. The aim of the present study
      was to describe and compare difficulties young and newly diagnosed women in
      Sweden and the United States experienced during their first year after diagnosis.
      METHOD: Three interviews, 6 months apart, were conducted, with 49 Swedish and 45
      US women between the ages of 18 and 39. Five open-ended questions were asked
      concerning physical, psychological and social difficulties and limitations, and
      factors that increased or decreased their difficulties and limitations. At
      interviews 2 and 3 the women were also asked about ways of preventing their
      difficulties. The answers were written down and analysed by a content analysis
      approach. RESULTS: Consistent categories of difficulties were reported: symptoms,
      movements, activities, moods, social network, external factors and coping
      strategies. More US women were working outside their homes than were their
      Swedish counterparts and they expressed more difficulties compared with the
      Swedish women. CONCLUSIONS: In general, difficulties decreased and coping
      strategies increased over the 1-year period in both groups of newly diagnosed,
      young women.

PMID- 17005480
TI  - A participatory program evaluation of a systems change program to improve access
      to information technology by people with disabilities.
AB  - PURPOSE: To pilot-test and evaluate an innovative program providing information
      technology (IT) access to people with disabilities transitioning out of nursing
      homes into the community using a participatory approach. METHODS: Pre- and post
      training data was collected on the 61 program participants to reflect three broad
      areas related to the IT training experience: performance; self-efficacy;
      importance, satisfaction and control. Additionally, semi-structured interviews
      were conducted with seven participants and five members of the program staff to
      explore environmental barriers to IT access for this group and the efficacy of
      the program in addressing these barriers. Data analyses followed a mixed methods
      approach incorporating both qualitative and quantitative techniques. RESULTS:
      Participants showed substantive changes in different spheres of IT use after
      completion of training. Post-training changes were significant particularly in
      areas related to self-efficacy, importance and satisfaction pertaining to use of
      IT. Qualitative findings substantiated the quantitative results and also revealed
      the numerous barriers to IT access that persons with disabilities continue to
      face within their communities. CONCLUSION: Results indicate the feasibility,
      effectiveness and value of IT access to people with disabilities particularly
      those transitioning from institutional life to community living. Further action
      research aimed at increasing IT access for this group within local communities
      and neighborhoods is needed to address this issue at a broader societal level.

PMID- 17005481
TI  - Psychological adjustment to lower limb amputation amongst prosthesis users.
AB  - PURPOSE: Clinical reports indicate that many lower limb amputees experience
      problems with psychological adjustment. Although depressive responses to
      amputation have been well investigated, there has been insufficient attention to
      other aspects of adjustment. This study aimed to determine the prevalence of
      psychological morbidity in an amputee population and identify variables
      associated with increased distress. Particular attention was given to cognitive
      models of emotion which postulate a key role for self-consciousness and
      appearance-related beliefs. METHOD: A cross-sectional survey of 67 adult lower
      limb prosthesis users who had experienced amputation within the last five years.
      Outcome measures were the Psychosocial Adjustment Scale of the Trinity Amputation
      and Prosthesis Experience Scales, the Hospital Anxiety and Depression Scale, the
      Self Consciousness Scale and the Appearance Schemas Inventory. RESULTS: Using
      conservative cut-off scores the prevalence of anxiety and depression was 29.9 and
      13.4%, respectively. Appearance-related beliefs were associated with both
      distress and psychosocial adjustment difficulties. Public but not private self
      consciousness was associated with distress and psychosocial adjustment
      difficulties. CONCLUSIONS: Clinicians need to monitor amputees for distress over
      a longer time period than the initial post-operative phase. It is particularly
      important to assess for anxiety. Interventions that target appearance-related
      beliefs may be of benefit to this population.

PMID- 17005482
TI  - The experience of being disabled and obese.
AB  - PURPOSE: This qualitative study was designed to explore the experiences of
      disabled and severely obese people living in the community. The challenges that
      their size and disabilities posed within their homes and in accessing community
      facilities were explored, with particular reference to the provision and use of
      assistive technologies. METHODS: The study comprised in-depth interviews with a
      sample of six severely obese, disabled people using a grounded theory approach.
      RESULTS: Three key themes emerged: the experience of daily life; accessing
      services; and responses to challenges. The study participants found that their
      home and community environments were seldom adequate for their size. Difficulties
      were identified in relation to accessing and using NHS services and negative
      attitudes and treatment from staff. Assessments and quality of assistive devices
      and housing adaptations received were criticised by some. Participants identified
      a range of responses to these challenges. CONCLUSION: The challenges that obesity
      bring are compounded by disability, including the need for higher levels of care
      and the higher costs of assistive devices for this client group. The study
      suggests there may be a need for training for professionals who work with obese,
      disabled people to ensure their needs are met in appropriate and cost-effective
      ways.

PMID- 17005483
TI  - The role of music therapy in an interdisciplinary approach to address functional
      communication in complex neuro-communication disorders: a case report.
AB  - PURPOSE: This paper presents a case report of collaborative work between speech
      and language therapy (SLT) and music therapy (MT) in the case of an individual
      presenting with complex communication difficulties and lability caused by pseudo
      Parkinsonian vascular disease. DESIGN: MT intervention was used to investigate
      whether participation could be enabled in a client presenting with complex
      problems as well as facilitate change in communication parameters which remained
      unresponsive to conventional SLT intervention. A single case design measured
      communication and well-being parameters using pre-, during and post-intervention
      measures. In addition, analysis of the client's musical responses was undertaken
      to examine changes in vocal functioning which are involved in communication.
      RESULTS: Analysis of the client's performance during MT intervention revealed
      improvements in prosody and phonation, with positive reports of participation,
      reduced incidence of lability and improvements in measures of well-being.
      CONCLUSIONS: The results indicate the value of such collaborative working in
      addition to making recommendations for the modification of existing treatment
      protocols. The findings highlight that fatigue is a major consideration when
      working with people with severe and complex clinical presentations.

PMID- 17005484
TI  - 'Optimal' participation: a reflective look.
AB  - PURPOSE: There is mounting interest by professionals working in the
      rehabilitation sciences related to the concept of participation, especially given
      the increasing numbers of individuals worldwide living with chronic illnesses. It
      is now internationally agreed that participation level is influenced by both
      personal and environmental factors. The question arises as to the meaning of
      'optimal' participation. The main objective of this article is to provide a
      reflective look at the concept of participation and the meaning of 'optimality'
      for individuals with and without disability and to explore both in relation to
      response shift. METHOD: Similarities in definitions of participation are first
      examined. Normal participation level is discussed leading to an 'optimal' level
      based on normality. Cases are used to illustrate normality as well as how
      'optimal' participation can be achieved through a transition period despite
      disabilities caused by a health condition such as a stroke. RESULTS: 'Optimal'
      participation would rely on a perfect fit between an individual's reality (how
      activities and roles are actually realised) and expectations of how activities
      and roles should be accomplished. A transition period, including a response
      shift, following an acute event or onset of a chronic condition can lead to an
      optimal participation level despite persisting disabilities. CONCLUSIONS: A
      better understanding of the meaning of optimal participation and its association
      to response shift is important to clinical practice. Interventions aimed at
      optimizing participation through assisting clients who are experiencing a
      response shift can then be designed to maximize participation and concomitantly,
      quality of life in those with chronic health conditions.

PMID- 17005485
TI  - Fitting range of the BAHA Cordelle.
AB  - The performance of the most powerful Bone-Anchored Hearing Aid (BAHA) currently
      available, the BAHA Cordelle, was evaluated in 25 patients with severe to
      profound mixed hearing loss. Patients showed bone conduction thresholds at 500,
      1000 and 2000 Hz, ranged between 30 and 70 dB HL, and an additional air-bone gap
      of about at least 30 dB. With the BAHA Cordelle, free-field thresholds improve
      relative to bone-conduction thresholds with 1.5, 5.0, 17.8, and 4.3 dB at 500,
      1000, 2000, and 4000 Hz, respectively, with substantial inter-individual
      variability. The differences in unaided air conduction thresholds and aided free
      field thresholds amount to 45.3, 45.8, 47.5, and 43.5 dB at 500, 1000, 2000, and
      4000 Hz, respectively. Speech perception, measured both with monosyllables of the
      consonant-vowel-consonant type and with bisyllables, showed highly similar
      results. The fitting range of a (linear) hearing aid is determined by its gain
      characteristics. Requiring aided speech reception thresholds at or better than 65
      dB SPL results in an upper limit of the fitting range of the BAHA Cordelle for
      bone-conduction thresholds of 51, 56, 67, and 58 dB HL at 500, 1000, 2000, and
      4000 Hz, respectively. The dynamic range provided by the BAHA Cordelle was
      estimated from loudness growth functions at 500, 1500, and 3000 Hz employing 7
      point categorical scaling. On average, aided loudness growth functions exhibit
      normal slopes but they level off at input levels of about 80, 70, 65 dB SPL for
      500, 1500, and 3000 Hz stimuli, respectively. Measurements with a skull simulator
      demonstrated that the levelling-off reflects saturation of the output of the
      Cordelle. The relatively low saturation levels of the device suggest that
      increasing maximum output levels may be a worthwhile consideration for candidates
      with more profound sensorineural loss.

PMID- 17005486
TI  - Deafened tutors' experiences of delivering the challenging deafness (CD) course:
      'recharging my motivational battery'.
AB  - The objective was to examine tutors' views regarding motivation to become a lay
      tutor on a generic, lay-led self-management programme, 'Challenging Deafness'
      (CD); their experience of course delivery; and the impact of being a tutor on
      their own lives. Eight tutors (6 male) were interviewed face-to-face. Data were
      analysed using content analysis. Motivation to become a tutor was associated with
      desire to help others and establish a new purpose in life. Tutors derived a
      satisfaction from sharing experiences with course participants and felt their
      contribution to the welfare of others was valued not only by course participants,
      but also by friends, family and society. Delivering CD courses reinforced tutors'
      own self-management, helped develop new skills (e.g. giving presentations), and
      enhanced confidence. Challenges associated with the tutor role included fatigue,
      travelling to venues, and managing some course participants. Although tutors felt
      supported in their role, some felt that advertising materials should reflect the
      psychosocial nature of the course. Several tutors suggested course modifications
      specific to the needs of deafened adults.

PMID- 17005487
TI  - Telephone use: what benefit do cochlear implant users receive?
AB  - This study evaluated the use of landline and mobile phones in an international
      sample of cochlear implant users. A custom-designed survey was mailed to cochlear
      implant users from four different countries. A link to the survey was posted on
      the MED-EL website, with responses from a further six countries. Results from 196
      surveys show that there is a significant shift from pre-operative non-use of a
      telephone to use of a telephone post-operatively. Seventy-one percent of MED-EL
      cochlear implant users are able to use a landline telephone to some extent and
      54% are able to use a mobile phone to some extent. Talking to familiar speakers
      about familiar topics is the easiest listening condition on the telephone, and it
      is easier to recognize a voice using the landline. Many respondents found it
      difficult to make a call without some assistance. Most respondents could manage
      to call someone in an emergency, even on a mobile phone. Data obtained should
      provide useful information in the counselling and rehabilitation of cochlear
      implant recipients and candidates.

PMID- 17005488
TI  - Simple reaction times in subjects with steeply sloping hearing loss: is there an
      alteration at the edge of the loss?
AB  - The aim of the present study was to investigate the simple reaction time (RT)
      performance of patients with steeply sloping sensorineural hearing loss. This
      kind of hearing loss has the particularity of inducing a reorganization of the
      primary auditory cortex (Dietrich et al, 2001), the edge frequency of the loss
      being over-represented. It is assumed that a consequence of this plasticity could
      be reflected in an improvement in frequency discrimination performances around
      the edge of the loss (McDermott et al, 1998). In the present study we used pure
      tones equalized in loudness to investigate whether RT might be altered at the cut
      off frequency (Fc) of the loss, or at the frequency that presented the best
      discrimination-limen-for-frequency (bDLF). The effect of auditory rehabilitation
      on RT was also studied. A great variability in RT was noted in all our subjects.
      Our results demonstrated that RT was unmodified at Fc or bDLF, be it before or
      after hearing aid fitting. However, an improvement in the correlation between RT
      and frequency discrimination performance was observed at three months post
      rehabilitation.

PMID- 17005489
TI  - Detecting dead regions using psychophysical tuning curves: a comparison of
      simultaneous and forward masking.
AB  - A dead region (DR) is a region of the cochlea where there are no functioning
      inner hair cells and/or neurones. We compared the edge frequencies, fe, of DRs
      estimated using four methods: the TEN(HL) test; psychophysical tuning curves
      (PTCs) measured in simultaneous masking (320-Hz wide noise masker) using a 'fast'
      method (sweeping masker) and a 'classical' method; and PTCs measured in forward
      masking (sinusoidal masker) using a 'classical' method. Fourteen subjects with
      high-frequency DRs were tested. For measurement of PTCs, the signal frequency was
      chosen to fall inside the DR; the tip frequencies of the PTCs were taken as
      indicating the values of fe. The values of fe obtained from the PTCs in forward
      and simultaneous masking (both fast and classical methods) were similar and were
      usually close to, but somewhat above, the values of fe estimated from the TEN(HL)
      test. Fast PTCs measured in simultaneous masking are recommended for use in
      clinical practice, as they give a precise estimate of fe and are quick to
      administer.

PMID- 17005490
TI  - Reliability of electric response audiometry using 80 Hz auditory steady-state
      responses.
AB  - The reliability of the Auditory Steady State Response (ASSR) has not been
      thoroughly evaluated despite its recent application as a clinical tool for
      threshold estimation. The purpose of this study was to examine test-retest (TR)
      reliability of ASSR threshold estimates in an empirical research design. The
      ASSR, tested using modulation frequencies approximately 80 Hz and above, was
      evaluated against pure tone audiometry (PTA), and the slow vertex potential (SVP,
      N1-P2). Sixteen normal-hearing young female adults were tested twice, one week
      apart. Varying degrees of sensorineural hearing loss of a notched configuration
      were simulated with filtered masking noise. Test-retest reliability was assessed
      using Pearson-product moment correlation analysis, supplemented by other post-hoc
      analyses. Results demonstrated moderately strong TR reliability for ASSR at 1000,
      2000 and 4000 Hz (r = 0.83-0.93); however, the reliability of ASSR at 500 Hz was
      weaker (r = 0.75). Results suggest that ASSR-ERA is a reliable test at mid-high
      frequencies, at least with the configuration and degrees of simulated
      sensorineural hearing loss examined in this study.

PMID- 17005491
TI  - Speech masking release in listeners with flat hearing loss: effects of masker
      fluctuation rate on identification scores and phonetic feature reception.
AB  - Consonant identification was measured for a stationary and amplitude-modulated
      noise masker in four listeners with flat cochlear hearing loss, and four age
      matched normal-hearing listeners. The masker modulation rate was systematically
      varied between 2 and 128 Hz. Masking release (MR), that is better identification
      performance in fluctuating, than in stationary noise, was highest in a masker
      fluctuating at 8-16 Hz in all normal-hearing listeners. In comparison, MR was
      only observed in two out of the four impaired listeners. In these listeners, MR
      was poorer than normal, and peaked at lower rates, that is 2 or 8 Hz. MR
      corresponded to increased reception of information for voicing, place, and manner
      between 2 and 64 Hz in all normal-hearing listeners. In impaired listeners,
      increased reception of information was mainly observed for manner, and mainly
      reduced for place, but these differences were not significant. For all phonetic
      features, MR was observed at lower masker fluctuation rates (< or =32 Hz) than in
      normal-hearing listeners. This study therefore shows that cochlear damage affects
      MR, both quantitatively and qualitatively.

PMID- 17005492
TI  - Psychological assessment of patients with Meniere's disease.
AB  - The objective of this study was to evaluate daily stressors, coping, personality,
      physical and mental health, and quality of life in Meniere patients. 110
      consecutive patients with definite Meniere's disease were assessed using the
      Dutch Daily Hassles List, Coping Inventory for Stressful Situations (CISS),
      Symptoms Checklist 90 (SCL-90), NEO Five Factor Inventory (NEO-FFI), General
      Health Questionnaire (GHQ-12), and the Short Form Health Survey 36 (SF-36).
      Duration and subjective severity of symptoms were scored using a self-report
      questionnaire. It was shown that Meniere patients had more daily stressors, used
      certain coping strategies less often, and had more psychopathology (e.g. anxiety
      and depression), and a worse quality of life compared to healthy reference
      groups. No abnormalities in personality were found. Patients with more severe
      symptoms had more psychopathology and a worse quality of life than patients with
      mild symptoms. The psychological profile of Meniere patients seems comparable to
      patients with other chronic diseases. The outcomes should be used to intensify
      psychological support in patients with this disabling disease.

PMID- 17005493
TI  - Occupational performance: comparing normally-hearing and hearing-impaired
      employees using the Amsterdam Checklist for Hearing and Work.
AB  - This study compares the occupational performance of employees with and without
      hearing impairment, and aims to identify occupational difficulties specifically
      related to hearing loss. The Amsterdam Checklist for Hearing and Work was
      administered to 150 hearing-impaired employees and 60 normally-hearing
      colleagues. A multivariate analysis of variance was performed to test group
      effects, and to examine differences between means. Factors predicting sick-leave
      were identified by regression analyses. A significant group effect (p < 0.01) was
      found. Hearing-impaired employees differed from normally-hearing colleagues in
      their perception of 'environmental noise', 'job control' and the 'necessity to
      use hearing activities' at work. Also, sick-leave due to distress occurred
      significantly more often in the hearing impaired group (p < 0.05). 'Hearing
      impairment', 'job demand', and the requirement to 'recognize/distinguish between
      sounds' were the strongest risk-factors for stress related sick-leave. The
      importance of hearing functions besides speech communication is discussed.
      Implications for rehabilitation are suggested. In future research, hearing loss
      should be considered as a risk factor for fatigue and mental distress which may
      lead to sick-leave.

PMID- 17005494
TI  - Learning to discriminate interaural time differences: an exploratory study with
      amplitude-modulated stimuli.
AB  - The advent of bilateral cochlear implants (CIs) has increased interest in
      learning on binaural tasks, and studies in normal-hearing listeners provide
      important background information. However, few studies have considered learning
      with discrimination of interaural time difference (ITD). Here, learning with ITD
      was explored using stimuli that are more relevant to bilateral CIs than used
      previously. Inexperienced listeners were trained with envelope-based ITD using
      high-frequency amplitude-modulated tones with or without an interaural carrier
      frequency difference (IFD), the former to simulate asymmetrical bilateral CI
      insertions. All were tested with and without IFD before and after training. In
      most listeners, ITD thresholds improved substantially with training, not
      necessarily reaching asymptote after 3,000 trials. In these, the magnitude and
      time-course of learning was larger than anticipated from a previous study with
      low-frequency ITD. Learning generalized across IFD and the effect of IFD on ITD
      thresholds at post-test was smaller than reported previously. These results have
      implications for studies of bilateral CIs, such as the need to provide extensive
      training to avoid over-estimating any apparent 'impairment'.

PMID- 17005495
TI  - The effect of gap-marker spectrum on gap-evoked auditory response from the
      inferior colliculus and auditory cortex of guinea pigs.
AB  - The objective of this study is to verify the effects of gap marker spectrum on
      gap-evoked auditory responses. The gap-evoked potentials were recorded using
      electrodes implanted in the inferior colliculus (IC) and auditory cortex (AC) of
      guinea pigs. The gap markers were noise bursts in four frequency bands (500-8,000
      Hz, 500-16,000 Hz, 500-32,000 Hz, and 16,000-32,000 Hz), and were tested at three
      sound levels. The onset response to the post-gap marker was measured to obtain
      the gap response threshold, and to establish input-output functions for latency
      and amplitude. Similar to previous behavioural studies, it was found that the gap
      response threshold decreased with increasing marker bandwidth. This change was
      more significant at the cortical level in which the averaged gap-threshold
      decreased by approximately 2 ms with the bandwidth change. However, the gap
      threshold in the high frequency region (16,000-32,000 Hz) was comparable to that
      of the low frequency region (500-16,000 Hz). These results suggest that the total
      bandwidth of all auditory channels that are recruited determine the temporal
      resolution measured in gap-evoked potentials.

PMID- 17005496
TI  - The prevalence of congenital and early-onset hearing loss in Jordanian and
      Israeli infants.
AB  - The objective of the study was to investigate the prevalence of congenital and
      early-onset hearing loss, and the influence of the known risk factors for hearing
      loss on infants in Jordan and Israel. Subjects were a total of nearly 17,000
      infants from both countries, including infants with and without risk factors for
      hearing loss. The hearing screening protocol included distortion product
      otoacoustic emission, followed in case of repeated OAE referral or high risk (HR)
      infant by diagnostic auditory brainstem responses. The results indicate that the
      prevalence and severity of hearing loss amongst Jordanian infants (1.37%) is
      remarkably higher as compared to the Israeli infants (0.48%). The overall
      prevalence of bilateral SNHL was seven times more in the Jordanian infants, 18
      times in non-risk, and three times in the HR infants relative to the Israeli
      infants. Risk factors including family history, hyperbilirubinemia, bacterial
      meningitis, and associated syndromes were more prevalent amongst Jordanian
      infants. This unique study underscores the importance of sharing and exchanging
      information to create empirical data to guide health-care providers in adapting
      protocols to the local constraints in developing countries.

PMID- 17005497
TI  - Intra- and postoperative electrode impedance of the straight and Contour arrays
      of the Nucleus 24 cochlear implant: relation to T and C levels.
AB  - The objective of this study was to investigate electrode impedance in cochlear
      implant recipients in relation to electrically evoked stapedius reflex
      measurements during surgery, and to electrode design, stimulation mode, and T and
      C levels over a nine month period after surgery. Seventy-five implant recipients,
      implanted with a Nucleus straight electrode array or a Contour array, were
      included. The results show that: (1) during surgery electrode impedance decreases
      markedly after electrically evoked stapedius reflex measurements, (2) after
      surgery, during the period without stimulation until speech processor switch-on,
      impedance increases, (3) after processor switch-on impedance decreases. The lower
      impedance values after a period of stimulation are found at the higher T and C
      levels. Impedances of the straight array electrodes are lower than those of the
      Contour array. The difference corresponds mainly to their respective surface
      areas. In addition, the straight array shows a larger increase of impedance in
      the apical direction than the Contour array, probably because of the larger fluid
      environment around the basal electrodes of the straight array.

PMID- 17005498
TI  - Identification of binaural integration deficits in children with the Competing
      Words Subtest: standard score versus interaural asymmetry.
AB  - The Competing Words Subtest is a commonly used dichotic listening test for
      assessing binaural integration in children suspected of having an auditory
      processing disorder. In 124 children, standard scores from the subtest suggested
      a binaural integration deficit in 23% of the children tested. Because standard
      scores are derived from the combined scores of both ears during the test,
      children with normal performance in one ear and weak performance in the other ear
      may be overlooked. For these children, a measure of interaural asymmetry may be a
      more sensitive indicator of a binaural integration deficit. When an age
      appropriate criterion for interaural asymmetry from the Competing Words Subtest
      was used, the incidence of a binaural integration deficit increased to 51% of the
      children tested. Four typical patterns of dichotic listening performance were
      identified based on results from the two scoring techniques.

PMID- 17005499
TI  - Is goal planning in rehabilitation effective? A systematic review.
AB  - OBJECTIVE: To determine the evidence regarding the effectiveness of goal planning
      in clinical rehabilitation. DESIGN: Systematic review. METHOD: MEDLINE, EMBASE,
      PsycINFO, CINAHL, AMED, Cochrane Central Register of Controlled Trials, Cochrane
      Database of Systematic Reviews, American College of Physicians (ACP) Journal
      Club, and the Database of Abstracts of Reviews of Effects (DARE) were searched
      for randomized controlled trials on the therapeutic effectiveness of goal
      planning in the rehabilitation of adults with acquired disability. Studies were
      categorized by patient population and the clinical context of the study. Data
      were analysed using best-research synthesis, based on methodological quality
      determined by Physiotherapy Evidence Database (PEDro) scale scores. RESULTS:
      Nineteen studies were included in this review. Study populations in these papers
      included patients with neurological disorders, psychiatric disorders,
      musculoskeletal disorders, cardiovascular disorders, respiratory disorders and
      dietary/endocrine disorders. Six studies investigated the immediate effects of
      goal planning on patient behaviour. Thirteen studies investigated the effects of
      goal planning in the context of a rehabilitation programme lasting more than one
      week. Some limited evidence was identified that goal planning can influence
      patient adherence to treatment regimes and strong evidence that prescribed,
      specific, challenging goals can improve immediate patient performance in some
      specific clinical contexts. However, evidence regarding how these effects
      translated to improved outcomes following rehabilitation programmes was
      inconsistent. CONCLUSIONS: This review identified that while some studies
      demonstrated positive effects associated with goal planning in local contexts,
      the best available empirical evidence regarding the generalizable effectiveness
      of goal planning was inconsistent and compromised by methodological limitations.

PMID- 17005500
TI  - Goal setting as an outcome measure: A systematic review.
AB  - BACKGROUND: Goal achievement has been considered to be an important measure of
      outcome by clinicians working with patients in physical and neurological
      rehabilitation settings. This systematic review was undertaken to examine the
      reliability, validity and sensitivity of goal setting and goal attainment scaling
      approaches when used with working age and older people. AIMS AND OBJECTIVES: To
      review the reliability, validity and sensitivity of both goal setting and goal
      attainment scaling when employed as an outcome measure within a physical and
      neurological working age and older person rehabilitation environment, by
      examining the research literature covering the 36 years since goal-setting theory
      was proposed. METHODS: Data sources included a computer-aided literature search
      of published studies examining the reliability, validity and sensitivity of goal
      setting/goal attainment scaling, with further references sourced from articles
      obtained through this process. MAIN FINDINGS: There is strong evidence for the
      reliability, validity and sensitivity of goal attainment scaling. Empirical
      support was found for the validity of goal setting but research demonstrating its
      reliability and sensitivity is limited. CONCLUSIONS: Goal attainment scaling
      appears to be a sound measure for use in physical rehabilitation settings with
      working age and older people. Further work needs to be carried out with goal
      setting to establish its reliability and sensitivity as a measurement tool.

PMID- 17005501
TI  - The effects of aerobic and resistance exercises in obese women.
AB  - OBJECTIVE: To compare the effects of aerobic and resistance exercise on weight,
      muscle strength, cardiovascular fitness, blood pressure and mood in obese women
      who were not on an energy-restricted diet. DESIGN: Randomized, prospective,
      controlled trial. SETTING: Department of Physical Medicine and Rehabilitation,
      University Hospital. SUBJECTS: Sixty obese women were assigned to one of three
      groups: aerobic exercise (n = 20), resistance exercise (n = 20) and control group
      (n = 20). INTERVENTIONS: The aerobic exercise group performed both walking and
      leg cycle exercise with increasing duration and frequency. The resistance
      exercise group performed progressive weight-resistance exercises for the upper
      and lower body. MAIN OUTCOME MEASURES: Before and after a 12-week period, all
      subjects were evaluated by anthropometric measurement, rating of mood,
      cardiorespiratory capacity and maximum strength of trained muscles. RESULTS:
      After a 12-week training period, subjects in the resistance group showed
      significant improvement in one-repetition maximum test of hip abductors (7.95+/
      3.58 kg), quadriceps (14+/-7.18 kg), biceps (3.37+/- 2.84 kg) and pectorals
      (8.75+/-5.09 kg) compared with those in the control group (P < 0.001). VO2 max
      increased (0.51+/-0.40) and Beck Depression Scale scores decreased (-5.40+/-4.27)
      in the aerobic exercise group compared with the control group, significantly (P <
      0.001). Only in hip abductor muscle strength was there a significant increase in
      the resistance exercise group compared with the aerobic exercise group (P <
      0.05). CONCLUSION: Both aerobic exercise and resistance exercise resulted in
      improved performance and exercise capacity in obese women. While aerobic exercise
      appeared to be beneficial with regard to improving depressive symptoms and
      maximum oxygen consumption, resistance exercise was beneficial in increasing
      muscle strength.

PMID- 17005502
TI  - A randomized controlled trial of a health promotion education programme for
      people with multiple sclerosis.
AB  - OBJECTIVE: To evaluate the effectiveness of a health promotion education
      programme for people with multiple sclerosis (the OPTIMISE programme) in terms of
      increasing the level of health-promoting activity undertaken, improving self
      efficacy and enhancing quality of life. DESIGN: A randomized controlled single
      blinded trial. Non-parametric analysis was undertaken to test for significant
      differences between treatment and control groups change scores. SUBJECTS AND
      SETTING: Sixty-two adults (32 treatment and 30 control subjects) with multiple
      sclerosis of any type, Expanded Disability Status Scale (EDSS) 1-7. INTERVENTION:
      An eight-week multidisciplinary outpatient health promotion education programme
      aimed at increasing knowledge, skills and confidence in undertaking health
      promotion activities. OUTCOME MEASURES: Health Promoting Lifestyle Profile, Self
      Rated Abilities for Health Practices Scale and the Short Form 36 Item Health
      Survey. RESULTS: Following completion of the programme, treatment subjects had
      significantly higher levels of health promotion activity undertaken (P < 0.01)
      and self-efficacy for health promotion activities (P < 0.01). These benefits were
      sustained for at least three months after the programme ceased. Certain domains
      of quality of life also improved in treatment subjects more than controls
      (physical P = 0.03, mental health and general health P = 0.01), although only
      mental health and general health showed further improvement at three months.
      Participants provided positive feedback regarding the usefulness of the
      intervention and demonstrated observable changes to their health promotion
      behaviours. CONCLUSIONS: The OPTIMISE programme produced significant changes in
      health-promoting behaviours.

PMID- 17005503
TI  - Measuring autonomy in disabled people: Validation of a new scale in a UK
      population.
AB  - OBJECTIVE: To evaluate the validity and reliability of an English version of the
      Impact on Participation and Autonomy Questionnaire (IPA). The original Dutch IPA
      has been shown to load onto five factors. DESIGN: A validation study. SETTING:
      Outpatients clinics and people's homes. SUBJECTS: Two hundred and thirteen people
      with multiple sclerosis, rheumatoid arthritis, spinal cord injury, and general
      practice attendees, stratified by level of disability (median age 54, 42% male,
      58% female). INCLUSION CRITERIA: English as first language, aged 18-75, Mental
      Status Questionnaire score >6. INTERVENTIONS: Self- and interviewer-administered
      outcome measures. MAIN MEASURES: IPA, including one new item (66 participants
      completed the IPA on a second occasion). OTHER MEASURES: Short Form-36 Health
      Survey (SF-36), London Handicap Scale, three domains of the Functional
      Limitations Profile (FLP): household management, social integration, emotion.
      RESULTS: Confirmatory factor analysis confirmed the construct validity of the IPA
      (Normal Fit Index = 0.98, Comparative Fit Index = 0.99), indicating a good fit to
      the model. Convergent and discriminant validity were confirmed by the predicted
      associations, or lack of, with the exception of a poor association between the
      'social life/relationships' IPA subscale and FLP-emotion. Internal reliability of
      the IPA was confirmed (Cronbach alphas >0.8; item-total correlations for all
      subscales >0.5). Test-retest reliability was confirmed for all items (weighted
      kappas >0.6) and subscales (intraclass correlation coefficients >0.90).
      CONCLUSIONS: The English IPA is a valid, reliable and acceptable measure of
      participation and autonomy in people with a range of conditions and can make a
      unique and fundamental contribution to outcome assessment. Further research is
      required to examine the responsiveness of the IPA to change over time, its
      clinical utility and suitability for use with people from ethnic minorities and
      with older people.

PMID- 17005504
TI  - Development and validation of a muscular dystrophy-specific functional rating
      scale.
AB  - OBJECTIVE: To develop a reliable and valid new rating scale for measuring the
      functional impact of muscular dystrophy. DESIGN: Prospective and longitudinal
      investigation. SETTING: Three academic medical centres in Taiwan and the Muscular
      Dystrophy Association of Taiwan. MEASURES: The Brooke Scale, the Vignos Scale,
      the Barthel Index, muscular strength, contracture severity, and predicted forced
      vital capacity (FVC%). METHODS: Scale development was in three stages. In stage
      I, a preliminary pool of 53 items was generated from patient interviews (n = 25),
      literature review, existing functional rating scales and expert opinion. In stage
      II, these items were administered to 85 patients with muscular dystrophy. The
      resulting data were analysed to construct a rating scale (the Muscular Dystrophy
      Functional Rating Scale, MDFRS) that encompassed four unidimensional constructs:
      mobility, basic activities of daily living, arm function and impairment. In stage
      III, the measurement properties of this rating scale were assessed in 121
      muscular dystrophy patients different from those examined with the preliminary
      instrument. RESULTS: Internal consistency reliability was excellent for all
      domains of the final 33-item scale, with values of Cronbach's alpha ranging from
      0.84 to 0.97. Intraclass correlation coefficients for test-retest and inter-rater
      reliability were 0.99 for all domains of the MDFRS. The MDFRS showed moderate to
      high correlations with a range of functional rating scales measuring similar
      aspects and impairment parameters (Spearman's rho = 0.65-0.91; P < 0.001, each).
      Confirmatory factor analysis supported a unitary construct of the four
      dimensional MDFRS. The MDFRS had small floor and ceiling effects in the study
      samples. Sensitivity to change was confirmed by large standardized response means
      for the MDFRS total score. CONCLUSIONS: The MDFRS is a reliable and valid disease
      specific measure of functional status for patients with muscular dystrophy.

PMID- 17005505
TI  - Life goals of patients with Parkinson's disease: A pilot study on correlations
      with mood and cognitive functions.
AB  - OBJECTIVE: To identify the life goals of people with Parkinson's disease, to
      assess whether patients felt that these goals were 'on track', and to assess the
      relation of these life goals to neuropsychologic and mood function. DESIGN: Cross
      sectional descriptive study with an age-matched control group. SETTING:
      Outpatient Movement Disorders Clinics Veterans Hospital. SUBJECTS: Twenty-two
      patients with mid-stage Parkinson's disease and 22 age-matched controls.
      MEASURES: Rivermead Life Goals Inventory, neuropsychological and mood scales.
      RESULTS: People with Parkinson's disease were less likely than age-matched
      controls to cite religion, social contacts, leisure activities and personal care
      as 'extremely important life goals'. People with Parkinson's disease assigned
      significantly lower 'importance' ratings to leisure activities and religion than
      did controls. In addition, people with Parkinson's disease assigned significantly
      lower 'on track' ratings for leisure activities, work, social contacts, religion
      and financial affairs compared with controls' rating on the same items. Although
      people with Parkinson's disease showed significantly greater levels of cognitive
      and mood dysfunction than did controls, their mean importance ratings on life
      goals correlated only with mood function scores. CONCLUSIONS: The leisure
      activities, work, social contacts, religion and financial affairs of people with
      Parkinson's disease are less 'on track' than are their personal and family
      relationships. Subjective importance ratings of particular life goals of people
      with Parkinson's disease were found to be significantly related to mood function
      and not to cognitive function. Goal derailment ratings on the other hand were
      significantly related to both mood and cognitive impairment.

PMID- 17005506
TI  - Manifestations of mental slowness in the daily life of patients with stroke: A
      qualitative study.
AB  - OBJECTIVE: To explore the consequences of mental slowness in the daily life of
      patients with stroke. DESIGN: In a cross-sectional survey semi-structured
      interviews were completed. Interviews were transcribed and coded by two
      independent reviewers. Qualitative analysis was done by means of the 'constant
      comparison method'. SETTING: Three rehabilitation centres in the Netherlands.
      PARTICIPANTS: A convenience sample of 13 patients with stroke, suffering from
      mental slowness, was derived from December 2003 to May 2004. MAIN OUTCOME
      MEASURES: Interview descriptions of the everyday consequences of mental slowness.
      RESULTS: Patients experienced many problems in daily life due to mental slowness.
      These could be divided into two main groups: (1) problems in cognitive
      functioning; (2) psychological and somatic complaints. In response to these
      problems, some patients mentioned the use of compensation strategies in order to
      reduce the demands on their information processing capacity. CONCLUSIONS: Mental
      slowness in cognitive functioning affects a wide range of activities, causing
      emotional symptoms in many patients and stimulating the spontaneous use of
      compensation strategies in some patients.

PMID- 17005507
TI  - Prophylaxis of postoperative vomiting in children undergoing tonsillectomy: a
      systematic review and meta-analysis.
AB  - Postoperative vomiting (POV) remains one of the commonest causes of significant
      morbidity after tonsillectomy in children. A variety of prophylactic anti-emetic
      interventions have been reported, but there has only been a limited systematic
      review in this patient group. A systematic search was performed by using Cochrane
      Controlled Trials Register, MEDLINE and EMBASE to identify double-blind,
      randomized, placebo-controlled trials of prophylactic anti-emetic interventions
      in children undergoing tonsillectomy, with or without adenoidectomy. The outcome
      of interest was POV in the first 24 h. Summary estimates of the effect of each
      prophylactic anti-emetic strategy were derived using fixed effect meta-analysis.
      Where appropriate, dose-response effects were estimated using logistic regression
      and 22 articles were identified. Good evidence was found for the prophylactic
      anti-emetic effect of dexamethasone [odds ratio (OR) 0.23, 95% CI 0.16-0.33], and
      the serotinergic antagonists ondansetron (OR 0.36, 95% CI 0.29-0.46), granisetron
      (OR 0.11, 95% CI 0.06-0.19), tropisetron (OR 0.15, 95% CI 0.06-0.35) and
      dolasetron (OR 0.25, 95% CI 0.1-0.59). Metoclopramide was also found to be
      efficacious (OR 0.51, 95% CI 0.34-0.77). There is not sufficient evidence to
      suggest that dimenhydrinate, perphenazine or droperidol, in the doses studied,
      are efficacious, nor were gastric aspiration or acupuncture. In conclusion,
      dexamethasone and the anti-serotinergic agents appear to be the most effective
      agents for the prophylaxis for POV in children undergoing tonsillectomy.

PMID- 17005508
TI  - Do we need inhaled anaesthetics to blunt arousal, haemodynamic responses to
      intubation after i.v. induction with propofol, remifentanil, rocuronium?
AB  - BACKGROUND: The aim of this study was to determine whether, after propofol,
      rocuronium and remifentanil rapid sequence induction, inhaled anaesthetic agents
      should be started before intubation to minimize autonomic and arousal response
      during intubation. METHODS: One hundred ASA I and II patients were randomized to
      receive 1 MAC of desflurane or sevoflurane during manual ventilation or not.
      Anaesthesia was induced with an effect-site-controlled infusion of remifentanil
      at 2 ng ml(-1) for 3 min. Patients then received propofol to induce loss of
      consciousness (LOC). Rocuronium (0.6 mg kg(-1)) was given at LOC and the trachea
      was intubated after 90 s of manual breathing support (=baseline) with or without
      inhaled anaesthetics. Vital signs and bispectral index (BIS) were recorded until
      10 min post-intubation to detect autonomic and arousal response. RESULTS: A
      significant increase in BIS value after intubation was seen in all groups. The
      increases were mild, even in those not receiving pre-intubation inhaled
      anaesthetics. However, in contrast to sevoflurane, desflurane appeared to
      partially blunt the arousal response. Heart rate, systolic and diastolic pressure
      increase similarly in all groups. CONCLUSIONS: Desflurane and sevoflurane were
      unable to blunt the arousal reflex completely, as measured by BIS, although the
      reflex was significantly less when desflurane was used. Rapid sequence induction
      with remifentanil, propofol and rocuronium and without inhaled anaesthetics
      before intubation can be done without dangerous haemodynamic and arousal
      responses at intubation after 90 s.

PMID- 17005509
TI  - Ultrasound-guided infrapatellar nerve block in human volunteers: description of a
      novel technique.
AB  - BACKGROUND: Despite the use of various treatment strategies arthroscopic knee
      surgery is still associated with clinically important postoperative pain. As the
      infrapatellar nerve (IPN) innervates vital anterior knee structures we decided to
      investigate the feasibility of a novel ultrasound-guided IPN block technique as a
      potential therapeutic option for out-patient arthroscopic knee surgery. METHODS:
      The IPN was blocked under ultrasonographic guidance in 10 adult volunteers using
      5 ml of levobupivacaine 5 mg ml(-1). Success rate, time to maximum cutaneous
      distribution of the block, distribution of cutaneous analgesia and time until
      full recovery of cutaneous sensation was noted as was the incidence of
      concomitant blockade of the saphenous nerve (SN). RESULTS: The IPN was
      successfully blocked in 9/10 subjects. However, a varying degree of concomitant
      SN block was observed as part of all blocks. The time to maximum cutaneous
      distribution of the block was 8.4 (sd 3.6) min and the duration until complete
      recovery of cutaneous sensation was 27.5 (19.1) h. CONCLUSION: Reliable blockade
      of the IPN can be achieved with ultrasonographic guidance. Because of the very
      close anatomical relationship between the IPN and the SN it appears inevitable to
      also get a variable degree of concomitant SN block. The duration of the IPN block
      was in the majority of subjects greater than 16 h, a finding that may make this
      block useful for postoperative analgesia in out-patient arthroscopic surgery.

PMID- 17005510
TI  - The Dutch experience with Health Impact Assessment of disasters.

PMID- 17005511
TI  - Recommendations to improve post-disaster HIA: planning before the disaster.

PMID- 17005512
TI  - The UK experience with Health Impact Assessment of disasters.

PMID- 17005513
TI  - Benign variations and incidental abnormalities of myocardial FDG uptake in the
      fasting state as encountered during routine oncology positron emission tomography
      studies.
AB  - Increased 18fluoro-2-deoxyglucose (FDG) uptake in the myocardium is frequently
      observed while performing clinical positron emission tomography (PET) body scans
      for oncology under fasting conditions. This article reviews the normal variations
      and abnormal appearances of myocardial FDG accumulation which are likely to be
      encountered in the routine PET studies. Knowledge about the myocardial glucose
      metabolism and specific abnormalities are indispensable in the interpretation of
      myocardial FDG uptake.

PMID- 17005514
TI  - Variation of mesorectal volume with abdominal fat volume in patients with rectal
      carcinoma: assessment with MRI.
AB  - The purpose of this study was to assess the variability in the volume of the
      mesorectum in patients with rectal carcinoma. A retrospective review was made of
      pelvic MRI studies in 30 patients (mean age 64 years, range 34-88 years, 18M:12F)
      with histologically proven rectal carcinomas that were confined to the
      mesorectum. The outer low signal margin of the mesorectum was traced, over at
      least 10 consecutive 10 mm contiguous slices, until its disappearance. The
      visceral fascial compartment, body cross-sectional area and body mass index were
      measured, on a solitary slice, at the level of the L5/S1 disc. Linear regression
      was calculated for independent determinants of the mesorectal volume. Mean
      mesorectal volume in males was 227.5 cm3 (95%CI 191.6-263.4), and in females was
      157.5 cm3 (95%CI 129.3-185.7). The difference in mesorectal volume between men
      and women was statistically significant (p<0.001). Mean visceral compartment area
      in males was 18.4 cm2 (95%CI 16.3-20.5) and in females was 14.6 cm2 (95%CI 12.8
      16.4). Visceral compartment area correlated with mesorectal area and volume in
      females (p<0.05), and extremely well in males (p<0.005). Body cross-sectional
      area, body mass index and age did not correlate with mesorectal size. The
      correlation of visceral compartment area with mesorectal volume and mean area
      suggests that the mesorectum is determined in a similar way to other body fat
      compartments, with a similar anatomical variation. This significant variation in
      size and volume may have an important prognostic implication in patients with
      rectal carcinoma. This volume can be measured and reported on pre-operative MRI
      scanning and may be communicated to surgeons and radiotherapists.

PMID- 17005515
TI  - Correlation between enhancement pattern of hepatocellular carcinoma on real-time
      contrast-enhanced ultrasound and tumour cellular differentiation on
      histopathology.
AB  - The objective of this study was to evaluate the correlation between the
      enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced
      ultrasound (CEUS) and tumour cellular differentiation on histopathology. 189 HCC
      lesions in 189 patients were retrospectively evaluated with CEUS and
      histopathological examination. CEUS was performed with SonoVue and contrast pulse
      sequencing. Histopathological diagnoses were made according to the Edmonson
      grading system. Significant differences were shown between the time that the HCC
      became hypoenhancing or remained echogenic in late phase and tumour cellular
      differentiation (p = 0.006; p = 0.036), but not with the time of commencement of
      hyperenhancing or commencement of isoenhancing in arterial phase and portal phase
      (p = 0.164, p = 0.113; p = 0.186, p = 0.070). The timing of HCC becoming
      hypoenhancing on CEUS is correlated with tumour cellular differentiation; well
      differentiated tumours wash out more slowly than poorly differentiated ones.

PMID- 17005516
TI  - 3D MRI in multiple sclerosis: a study of three sequences at 3 T.
AB  - The objective of this study was to assess the feasibility of using 3D acquisition
      at 3 T for imaging patients with multiple sclerosis (MS). Feasibility was
      assessed by three criteria based on acquisition time, specific absorption rate
      (SAR) and image quality. 47 patients with clinically definite MS underwent
      imaging in a Siemens 3T Trio MR scanner. Patient safety data were obtained
      following the scan sessions. The study had local ethics approval. The following
      three-dimensional (3D) sequences, all acquired coronally, were used: T2 fluid
      attenuated inversion recovery (FLAIR) (repetition time (TR) 6000 ms, echo time
      (TE) 353 ms, inversion time (TI) 2200 ms), 0.5x0.5x1 mm voxels, acquisition time
      10 min 38 s; T2 turbo spin echo (TSE) (TR 3000 ms, TE 354 ms), 1x1x1 mm voxels,
      acquisition time 8 min 29 s; T1 inversion recovery (IR) (TR 2040 ms, TE 5.56 ms,
      TI 1100 ms), matrix 512x448 (0.5x0.5 mm pixels), 0.5x0.5x1 mm voxels, acquisition
      time 7 min 38 s. Total acquisition time was 26 min 45 s. Example images are
      presented. 3D scanning at 3 T provides highly detailed, high quality images with
      acquisition times tolerated by MS patients, even by those with severe disability.
      The volumetric data are suitable for a wide variety of post-processing
      techniques; the authors suggest that 3D studies at 3 T should be considered as
      the possible brain imaging protocol for either cross-sectional or longitudinal
      studies in MS and that the 3D T2 FLAIR sequence should be considered for the
      purposes of radiological diagnosis.

PMID- 17005517
TI  - Design and implementation of an electronic data recording and processing system
      for physics quality control checks in external beam radiotherapy.
AB  - Quality control (QC) of external beam radiotherapy equipment ensures that
      commissioning performance is maintained. Paper based data recording is still used
      for QC, but this is resource intensive in terms of data calculation and
      processing. Electronic systems of data recording have many advantages; for
      example, they facilitate the analysis of data on a regular basis, allowing the
      user to examine the "health" of each machine; they help review and audit local
      frequencies of each check and can possibly predict component failure. They also
      allow for secure calculation of results and automatic charting for routine trend
      analysis. Initially, data recording at our centre was paper-based for daily,
      weekly and monthly checks. This paper system has been successfully replaced with
      an electronic system for QC data recording and processing for linear accelerators
      and superficial units. The system makes use of personal digital assistants and
      networked laptops for online recording of data, and networked desktop PCs for
      offline work. The systems of data recording have been designed using the power of
      macros within Microsoft Excel, which automatically calculate each QC parameter
      and charts the data recorded for long-term analysis of trends. As of the
      beginning of 2006, these systems have been fully implemented. The benefits of
      implementing such a system are numerous, for example, central storage, backup and
      archiving of data, for greater security and reducing operator errors in
      calculations. Other benefits are discussed within the paper. In the future, we
      hope to develop similar systems of data recording for QC checks on other
      radiotherapy equipment.

PMID- 17005518
TI  - Comparison of plain chest radiography and high-resolution CT in human
      immunodeficiency virus infected patients with community-acquired pneumonia: a sub
      Saharan Africa study.
AB  - The objective of the study was to determine the proportion of patients with
      missed lesions on plain chest radiographs compared with high-resolution computed
      tomography (HRCT) in 49 human immunodeficiency virus (HIV) infected patients with
      community-acquired pneumonia (CAP). Patients underwent plain chest radiography
      and HRCT scans of the chest at admission. Microbiological investigations for CAP
      were performed. An experienced radiologist, without knowledge of clinical or
      pathological data, reported the chest radiographs and HRCT scans. The study group
      included 26 females and 23 males, aged 18-53 years (mean age 36 years). Organisms
      were isolated from 26 patients (53%). In 40 patients (82%), the HRCT scans
      demonstrated lesions not visualized on the plain chest radiographs. There was
      100% correlation between plain radiographic and HRCT scan findings in nine cases
      (18%). Lesions that were not visualized on the plain radiographs but elucidated
      on HRCT included: pleural effusion (n = 14), ground-glass opacification (n = 20),
      pericardial effusion (n = 8), cavitation (n = 4), cysts (n = 4), bullae (n = 4),
      abscess (n = 1) and pneumothorax (n = 1). In 20 of 23 cases, hilar
      lymphadenopathy, identified on HRCT, was not recognized on plain chest
      radiographs. In patients in whom an organism was isolated, a correct HRCT
      diagnosis of pulmonary tuberculosis, bacterial pneumonia and Pneumocystis carinii
      pneumonia (PCP) was made in 80%, 84% and 100% of cases, respectively. The
      proportion of patients with missed lesions on plain chest radiographs in HIV
      infected patients with CAP was high. This has important implications for
      management and prognosis. HRCT scans correlate well with the microbiological
      diagnosis when reported by an experienced radiologist.

PMID- 17005519
TI  - The importance of a correct evaluation of progression in studies on chronic
      kidney disease.

PMID- 17005520
TI  - Up-regulation of adhesion molecule expression in glomerular endothelial cells by
      anti-myeloperoxidase antibody.
AB  - BACKGROUND: Anti-neutrophil cytoplasmic antibody directed against myeloperoxidase
      (MPO-ANCA) has been implicated in pauci-immune crescentic glomerulonephritis. It
      stimulates primed neutrophils to adhere to glomerular endothelial cells (GECs),
      thereby releasing reactive oxygen and other toxic substances and ultimately
      damaging the GECs. Though, a pathogenic role for MPO-ANCA is not fully
      understood, we hypothesized that MPO-ANCA modulates GEC functions by the
      increases in expression of adhesion molecules. METHODS: A polyclonal rabbit anti
      recombinant mouse MPO antibody (anti-rmMPO IgG) was evaluated in mouse GEC (mGEC)
      for its effect on adhesion molecule expression. The primary culture of mGEC was
      incubated with anti-rmMPO IgG or isotype control and the expression of
      intercellular adhesion molecules-1 (ICAM-1) was evaluated by real-time reverse
      transcription-polymerase chain reaction (RT-PCR) analysis and ICAM-1 cell ELISA.
      RESULTS: The real-time RT-PCR analysis showed that a treatment with 100 microg/ml
      anti-rmMPO IgG increased the expression of mRNAs for ICAM-1, vascular cell
      adhesion molecule-1 and E-selectin by approximately 12.5, 7.5 and 10.5-fold,
      respectively. ICAM-1 cell ELISA also substantiated increased expression of ICAM
      1. This enhancement of ICAM-1 expression was mediated by the antigen specificity
      of anti-rmMPO IgG. In addition, there were several proteins in mGEC specifically
      immunoprecipitated with anti-rmMPO IgG. CONCLUSIONS: These results showed that
      anti-MPO antibody activates not only neutrophils, but also GEC, indicating that
      anti-rmMPO IgG-induced direct activation of GEC contributes to neutrophil
      adhesion to GEC, thereby increasing glomerular neutrophil infiltration in
      initiation and progression of pauci-immune glomerulonephritis.

PMID- 17005521
TI  - ABO-incompatible transplantation--a safe way to perform renal transplantation?

PMID- 17005522
TI  - Inherent high peritoneal transport and ultrafiltration deficiency: their mid-term
      clinical relevance.
AB  - BACKGROUND: High peritoneal transport has been associated with poorer outcome in
      peritoneal dialysis (PD) patients, but not necessarily because of PD-dependent
      conditions. Our primary objective was to analyse the influences of baseline
      peritoneal small solute transport and ultrafiltration (UF) capacity on patient
      and technique survival, after adjusting for comorbid conditions. A secondary
      objective was to determine whether high transport was associated with basal
      comorbidity. METHODS: In this prospective observational patient/technique
      survival study, we followed 410 patients who started PD. At the baseline, we
      collected data to define comorbidities, tally the Charlson index, determine the
      baseline mass transfer area coefficients (MTAC) of urea and creatinine, net UF,
      plasma albumin and residual renal function (RRF). No data other than the
      information on patient and technique survival were recorded after baseline.
      RESULTS: The mean follow-up was 33 +/- 28 months. Dropouts during the study were
      due to renal transplantation in 140 cases, death in 142 cases and transfer to
      haemodialysis (HD) in 77 cases. Patients with inherent UF deficiency, high
      transport rate or both were not significantly different in the survival analysis
      from the rest. In the Cox hazards analysis, only age, Charlson index and a lower
      RRF were the significant mortality risk factors. None of the baseline parameters
      studied was a predictor of technique failure. High transporter patients had lower
      plasma albumin and UF capacity, comorbidity and more frequent liver diseases than
      the rest. Moderate to severe liver disease (n = 14) was significantly associated
      with the inherent high transport status, but was never accompanied by UF failure
      (UFF). UFF patients showed higher RRF, creatinine-MTAC and age. CONCLUSIONS:
      Neither the high transport nor the inherent UFF status has any influence on
      patient and technique survival. The inherent high small solute transport status
      is associated with hypoalbuminaemia and a greater comorbidity index. The Charlson
      index, age and lower RRF are the only independent predictors of mortality.
      Technique dropout is not predicted by any of the variables studied at the
      baseline.

PMID- 17005523
TI  - Streptococcal PD peritonitis--a 10-year review of one centre's experience.
AB  - BACKGROUND: Detailed descriptive studies focusing on streptococcal peritonitis in
      patients on peritoneal dialysis are lacking. Most of the current information is
      available through isolated case reports. METHODS: We conducted a retrospective
      analysis of our peritoneal dialysis (PD) peritonitis database over the last
      decade to study the clinical profile and treatment outcomes of streptococcal
      peritonitis. RESULTS: A total of 68 patients (age: 57.12 +/- 16.6 years; male:
      58.7%) with 104 episodes of streptococcal peritonitis (11.7% of total
      peritonitis) were identified. Of the patients, 18 (26.4%) were considered
      immunocompromised [failed renal transplant, systemic lupus erythematosus (SLE)]
      and 28 (41.1%) had diabetes. Streptococcus viridans accounted for the majority
      (94 episodes: 90.3%) of the streptococcal peritonitis. One patient developed S.
      viridans peritonitis after dental cleaning without antibiotic prophylaxis. Two
      (1.9%) infections with S. agalactiae and S. bovis each and seven (6.7%) with non
      haemolytic Streptococcus were noted. Three patients had hospital-acquired
      infection. Twenty-six (25%) episodes needed 8 +/- 5.9 days of hospitalization.
      Concurrent infection with two organisms accounted for 17 (16.3%) episodes.
      Cefazolin (71) and vancomycin (29) were the primary antibiotics used for the
      treatment. Five episodes needed two antibiotics and one patient required
      antifungal treatment. A third of the patients (33.3%) had peritonitis that
      resolved slowly, although the majority of those (94%) did ultimately resolve with
      antibiotics alone. Five (4.8%) episodes required removal of the PD catheter.
      Three of them were associated with dual infections (one each with yeast,
      Stenotrophomonas and Enterococcus). Relapse occurred in eight (7.6%) episodes,
      and 11 (10.5%) recurred over the period from 4 weeks to 6 months after treatment.
      CONCLUSIONS: Streptococci remain a significant cause of PD peritonitis. Viridans
      strep is the primary subtype responsible. Isolated infections with these
      organisms are associated with slower response, good outcome and higher rates of
      recurrence.

PMID- 17005524
TI  - Up-regulation of adiponectin, its isoforms and receptors in end-stage kidney
      disease.
AB  - BACKGROUND: Despite the favourable effects of adiponectin on the vasculature and
      insulin resistance (IR), levels are increased in patients with end-stage kidney
      disease (ESKD), in whom both IR and atherosclerosis are prevalent. METHODS: To
      investigate this paradox, we examined the distribution of adiponectin isoforms,
      the expression of adiponectin receptor (AdipoR) mRNA on peripheral blood
      mononuclear cells (PBMC) in 41 patients with ESKD on haemodialysis and 41 matched
      controls, and its function by adenosine monophosphate-activated protein kinase
      (AMPK) phosphorylation of AdipoR on PBMC. We also compared the expression of
      AdipoR on PBMC with that on muscle and subcutaneous and visceral fat in 10
      patients undergoing elective cholecystectomy. RESULTS: The proportion of the high
      molecular weight (HMW) isoform of adiponectin was increased in the dialysis group
      (P = 0.001), even though these patients were significantly insulin resistant
      compared with controls (P = 0.006). AdipoR1 and AdipoR2 on PBMC were also
      increased in patients with ESKD (P < 0.05 and P = 0.007, respectively), but
      levels did not correlate with IR, the HMW isoform or other anthropometric
      measurements. There was a strong correlation between AdipoR1 and AdipoR2 on PBMC
      in ESKD and in subcutaneous and visceral fat in controls. However, there was no
      relationship between AdipoR in PBMC, muscle or visceral fat. Phosphorylation of
      AMPK by recombinant adiponectin showed that AdipoR on PBMC, from controls and
      ESKD patients, were equally functional. CONCLUSIONS: IR in ESKD is not explained
      by the change in isoformic distribution, or by AdipoR down-regulation or
      dysfunction. Rather, this receptor-ligand axis is up-regulated and may be a
      beneficial response to the inflammatory milieu of ESKD.

PMID- 17005525
TI  - Functional impairment of monocyte-derived dendritic cells in patients with severe
      chronic kidney disease.
AB  - BACKGROUND: Dendritic cells (DCs) are antigen-presenting cells that are pivotal
      for the initiation of the primary immune response. Patients with chronic kidney
      disease (CKD) with or without chronic intermittent haemodialysis (CIHD) show an
      impaired immune response. Dysfunction of DCs may underlie this phenomenon.
      METHODS: In this study, several different functions of monocyte-derived DCs
      (moDC) of patients with CKD class IV-V (glomerular filtration rate <30 ml/min)
      and patients on CIHD were studied in vitro and compared with age- and sex-matched
      healthy volunteers. RESULTS: We demonstrate that, independent of the maturation
      stimulus used, mature moDC from both groups of patients did not acquire the same
      level of terminal differentiation as moDC from controls, as shown by analysis of
      cell surface markers and the relative high macropinocytosis activity of moDC. The
      stimulation of allogeneic T-cells by immature moDC and mature moDC did not differ
      between patients and controls. However, in the presence of immature moDC or
      antigen-loaded maturated moDC from patients, less proliferation of autologous T
      cells was observed in response to recall antigens. There was no difference
      between moDC from controls and patients in their ability to activate naive T
      cells and to differentiate them into Th1 and Th2 cells. CONCLUSIONS: These
      results show that the terminal differentiation of moDC in patients with severe
      CKD is impaired. This impairment is not restricted to one maturation stimulus and
      is independent of treatment with haemodialysis.

PMID- 17005526
TI  - Clinical biocompatibility of a neutral peritoneal dialysis solution with minimal
      glucose-degradation products--a 1-year randomized control trial.
AB  - BACKGROUND: Chronic utilization of a bio-incompatible peritoneal dialysis (PD)
      solution with acidic pH and a high content of glucose degradation product (GDP)
      has been implicated as a contributing cause of peritoneal failure. We compared a
      newly formulated solution of neutral pH and low levels of GDP to a standard PD
      solution. METHODS: Fifty new PD patients were randomized to a conventional
      lactate-buffered fluid (control) and a pH neutral, lactate-buffered, low GDP
      solution (balance). Patients were followed for 12 months. Serum samples were
      assayed for C-reactive protein (CRP). PD effluent was collected and assayed for
      cancer antigen-125 (CA125) and hyaluronan (HA). Clinical end points were the
      residual renal function and dialysis adequacy indices. RESULTS: After 52 weeks of
      treatment, PD fluid CA125 rose from 2.45 +/- 0.96 to 14.30 +/- 2.17 U/ml (P <
      0.001), and HA declined from 2.26 +/- 0.60 to 1.45 +/- 0.32 mug/ml (P = 0.07) in
      the balance group. The balance group had a higher PD fluid CA-125 (14.30 +/- 2.17
      vs 7.36 +/- 2.23 U/ml, P = 0.007), lower HA (1.45 +/- 0.32 vs 2.55 +/- 0.32
      mug/ml, P = 0.007), and lower serum CRP level (1.77 +/- 0.42 vs 7.73 +/- 2.42
      mg/l, P = 0.026) than the control group at 52 weeks. There was no difference in
      dialysis adequacy indices, ultrafiltration volume, urine output, residual renal
      function, peritonitis rate or need of hospitalization in 1 year. CONCLUSION: As
      compared to conventional PD solution, the use of balance, a neutral pH, low GDP
      solution resulted in a superior profile of PDE mesothelial cell marker and a
      lower degree of systemic inflammation, and the difference was maintained for 1
      year. It remains to be determined whether these effects could result in better
      long-term clinical outcome.

PMID- 17005527
TI  - Effective control of persistent hyperparathyroidism with cinacalcet in renal
      allograft recipients.
AB  - BACKGROUND: Cinacalcet rapidly normalizes serum calcium and reduces intact
      parathyroid hormone (PTH) levels in renal transplant patients with hypercalcaemia
      and persistent hyperparathyroidism. The aim of this study is to evaluate the 6
      months efficacy of cinacalcet and the effect of cinacalcet withdrawal on serum
      calcium and PTH in such patients. Furthermore, the impact of cinacalcet on bone
      turnover and quality of life was assessed. METHODS: Twelve renal allograft
      recipients with hypercalcaemia due to persistent hyperparathyroidism were treated
      with cinacalcet for 26 weeks. Cinacalcet was then withdrawn to check for
      recurrence of hypercalcaemia. RESULTS: Cinacalcet maintained normocalcaemia in
      all patients from week 4 to 26, and PTH significantly decreased and remained
      suppressed. Serum phosphate increased, whereas the serum calcium-phosphate
      product remained unchanged. The excretion of calcium and phosphate in the 24 h
      urine had tendency to decrease. After cinacalcet was withdrawn, hypercalcaemia
      recurred rapidly and PTH increased to baseline values. Renal function remained
      stable, proteinuria was unchanged and no allograft rejection was observed. During
      treatment with cinacalcet, total and bone-specific alkaline phosphatase
      increased, whereas the urinary deoxypyridinoline-creatinine ratio did not change
      significantly, suggesting enhanced bone formation. Quality of life assessed at
      weeks 10 and 26 remained unchanged compared with baseline. CONCLUSIONS: In
      conclusion, continued treatment with cinacalcet is required to maintain long-term
      normocalcaemia and to suppress the enhanced PTH production in renal transplant
      recipients with persistent hyperparathyroidism.

PMID- 17005528
TI  - Peritoneal transport characteristics and dwelling time significantly impact
      ghrelin clearance in peritoneal dialysis patients.
AB  - BACKGROUND: Plasma ghrelin exerts widespread bioactivities. Although it is
      effectively removed from the blood by a single course of haemodialysis,
      peritoneal clearance of ghrelin is uncertain. Our study aimed to determine (i)
      whether there is a correlation between plasma ghrelin levels and characteristics
      of peritoneal ghrelin clearance, and (ii) whether plasma ghrelin levels
      significantly impact markers of mortality or morbidity in continuous ambulatory
      peritoneal dialysis (CAPD) patients. METHODS: We enrolled 50 qualified CAPD
      patients. Blood was drawn during the fasting state and 2 h post-prandially. Also
      during these periods, peritoneal effluents were collected for radioimmunoassay of
      total plasma ghrelin level and measurement of other parameters. Twenty-four hour
      ascites were collected for determination of ghrelin daily mass transfer. RESULTS:
      Peritoneal ghrelin clearance was positively correlated with the dialysate
      peritoneal creatinine (D/P(Cr)) ratio. Fasting plasma ghrelin levels were
      inversely correlated with the peritoneal/plasma (D/P(ghrelin)) ratio (P = 0.045).
      Plasma ghrelin levels were negatively correlated with body mass index, waist-hip
      ratio, fasting insulin and triglyceride level, and positively correlated with
      lean body mass. Plasma ghrelin levels were positively correlated with left
      ventricular mass (LVM), left ventricular mass index and blood pressure.
      CONCLUSIONS: Peritoneal transporter characteristics may modulate plasma ghrelin
      levels in CAPD subjects. By contributing to the level of plasma ghrelin, dwelling
      time may have an impact on LVM and associated morbidity in CAPD patients.

PMID- 17005529
TI  - Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end
      stage diabetic nephropathy.
AB  - BACKGROUND: The MTHFR C677T single nucleotide polymorphism TT genotype is
      associated with increased levels of plasma homocysteine and possibly an effect on
      cardiovascular mortality. We evaluated the effect of C677T genotype on mortality
      in a large end-stage renal disease (ESRD) cohort. METHODS: C677T genotype was
      determined in 439 Caucasians with end-stage diabetic nephropathy (DNP) (cases)
      recruited from 30 dialysis centres in Southern Germany. A total of 482 type 2
      diabetes patients without DNP (no microalbuminuria) at inclusion served as a
      genotype control collective. Patients were prospectively followed for 4 years.
      Primary endpoint was all-cause mortality. RESULTS: In contrast to controls, the
      genotype distribution in cases was not in Hardy-Weinberg equilibrium (HWE, P =
      0.003), due to a less than expected number of patients with the TT genotype. The
      requirements of HWE were met in cases with < 2 years dialysis therapy prior to
      study inclusion (n = 219). TT genotype was associated with a decreased body mass
      index (P = 0.002) and long diabetes duration in dialysis patients (P = 0.03).
      However, TT genotype was not associated with an increased risk of all-cause or
      cardiac mortality in the total dialysis collective or the subgroup. Also, we
      observed no association of MTHFR genotype with cardiovascular morbidity in cases
      or controls (P > 0.05), or with an increased rate of progression to novel
      microalbuminuria. CONCLUSION: MTHFR 677TT genotype was significantly
      underrepresented in patients with ESRD in our study, but was not associated with
      premature mortality in these patients. We found no evidence for survival bias due
      to C677T genotype in the ESRD cohort, or bias due to genetically determined
      accelerated progression to novel microalbuminuria in the controls. However, we
      cannot exclude that the TT genotype protects from progression from
      microalbuminuria to more advanced stages of DNP, or that TT genotype is
      associated with premature mortality before a patient progresses to ESRD.

PMID- 17005530
TI  - High glucose increases the expression of Cbfa1 and BMP-2 and enhances the
      calcification of vascular smooth muscle cells.
AB  - BACKGROUND: Vascular calcification is common in diabetes but the pathogenesis is
      poorly understood. METHODS: To investigate the pathogenesis, we first examined
      the histology of inferior epigastric arteries from diabetic and non-diabetic
      patients undergoing a renal transplant. To examine the role of hyperglycaemia,
      bovine vascular smooth muscle cells (BVSMCs) were incubated with normal (5 mM) or
      high glucose (25 mM) for 48 or 72 h. RESULTS: The results demonstrated that
      diabetic patients, compared with non-diabetic patients, had significantly greater
      calcification and increased expression of the bone matrix proteins osteopontin,
      type I collagen, bone sialoprotein and alkaline phosphatase (ALP). The in vitro
      studies demonstrated that high glucose increased the expression of the osteoblast
      transcription factor core binding factor alpha subunit 1 (Cbfa1) and its
      downstream protein osteocalcin by 1.9-fold and 1.8-fold, respectively, and ALP
      activity by 1.5-fold. These findings were blunted in the presence of an inhibitor
      to protein kinase C. High glucose also significantly enhanced calcification in
      BVSMC in a time-dependent manner (2.20 +/- 0.50 vs 1.35 +/- 0.55 micromol/mg, day
      7; 5.04 +/- 1.35 vs 3.12 +/- 0.92 micromol/mg, day 14; P < 0.05). High glucose
      also induced the secretion of bone morphogenetic protein-2, a known
      osteoinductive factor, and further increased the secretion normally seen during
      calcification by 43% at day 7 and 57% at day 14. CONCLUSIONS: These results
      demonstrate that vascular calcification in patients with diabetes is a cell
      mediated process characterized by a phenotypic change of VSMCs to osteoblast-like
      cells with increased bone matrix protein expression, and that hyperglycaemia may
      directly induce these changes.

PMID- 17005531
TI  - Beyond phosphate--role of uraemic toxins in cardiovascular calcification.

PMID- 17005532
TI  - Trials and trade-offs in haemodialysis vascular access monitoring.

PMID- 17005533
TI  - Aneurysm of the membranous septum causes pre-syncopes and transient bilateral
      blindness.

PMID- 17005534
TI  - Low response to clopidogrel is associated with cardiovascular outcome after
      coronary stent implantation.
AB  - AIMS: To assess whether low response to clopidogrel influences cardiovascular
      outcome after coronary stent implantation in a consecutively measured cohort of
      patients with coronary stent implantation. METHODS AND RESULTS: A total of 379
      consecutive patients with symptomatic coronary artery disease (CAD), (stable
      angina n = 206 and acute coronary syndrome, n = 173) treated with percutaneous
      coronary stenting were enrolled in this trial. Responsiveness to clopidogrel was
      assessed by ADP (20 micromol/L)-induced aggregometry at least 6 h (mean 34.8+/
      25.9 h) after administration of a loading dose of 600 mg clopidogrel. Platelet
      inhibition < 30% was defined as low response to clopidogrel. At 3-month follow
      up, the primary outcome of a combined major cardiovascular event including non
      fatal myocardial infarction, non-fatal ischaemic stroke, or cardiovascular death
      was evaluated. Twenty-two patients (5.8%) were classified as low responders.
      Compared with patients who adequately responded to clopidogrel, a low responder
      had a significantly higher risk of major cardiovascular events [22.7 vs. 5.6%;
      odds ratio, 4.9; 95% confidence interval (CI), 1.66-14.96; P = 0.004]. After
      adjustment for other factors influencing cardiovascular outcome, low response to
      clopidogrel and severe left ventricular dysfunction were independently associated
      with a major cardiovascular event within 3 months (hazard ratio for low response
      to clopidogrel, 3.71; 95% CI, 1.08-12.69; P = 0.037). CONCLUSION: Low response to
      clopidogrel in patients with symptomatic CAD treated by stenting significantly
      enhances the occurrence of cardiovascular events and death. The evaluation of low
      response to clopidogrel may help to identify patients at increased risk who may
      benefit from intensified antiplatelet strategy.

PMID- 17005535
TI  - CAPS: coevolution analysis using protein sequences.
AB  - Coevolution Analysis using Protein Sequences (CAPS) is a PERL based software that
      identifies co-evolution between amino acid sites. Blosum-corrected amino acid
      distances are used to identify amino acid co-variation. The phylogenetic sequence
      relationships are used to remove the phylogenetic and stochastic dependencies
      between sites. The 3D protein structure is used to identify the nature of the
      dependencies between co-evolving amino acid sites. Friendly interpretable output
      files are generated. AVAILABILITY: CAPS version 1 is available at
      http://bioinf.gen.tcd.ie/~faresm/software/caps/. Distribution versions for
      Linux/Unix, Mac OS X and Windows operating systems are available, including
      manual and example files.

PMID- 17005536
TI  - Support vector machines for prediction of dihedral angle regions.
AB  - MOTIVATION: Most secondary structure prediction programs target only alpha helix
      and beta sheet structures and summarize all other structures in the random coil
      pseudo class. However, such an assignment often ignores existing local ordering
      in so-called random coil regions. Signatures for such ordering are distinct
      dihedral angle pattern. For this reason, we propose as an alternative approach to
      predict directly dihedral regions for each residue as this leads to a higher
      amount of structural information. RESULTS: We propose a multi-step support vector
      machine (SVM) procedure, dihedral prediction (DHPRED), to predict the dihedral
      angle state of residues from sequence. Trained on 20,000 residues our approach
      leads to dihedral region predictions, that in regions without alpha helices or
      beta sheets is higher than those from secondary structure prediction programs.
      AVAILABILITY: DHPRED has been implemented as a web service, which academic
      researchers can access from our webpage http://www.fz-juelich.de/nic/cbb

PMID- 17005537
TI  - BNArray: an R package for constructing gene regulatory networks from microarray
      data by using Bayesian network.
AB  - BNArray is a systemized tool developed in R. It facilitates the construction of
      gene regulatory networks from DNA microarray data by using Bayesian network.
      Significant sub-modules of regulatory networks with high confidence are
      reconstructed by using our extended sub-network mining algorithm of directed
      graphs. BNArray can handle microarray datasets with missing data. To evaluate the
      statistical features of generated Bayesian networks, re-sampling procedures are
      utilized to yield collections of candidate 1st-order network sets for mining
      dense coherent sub-networks. AVAILABILITY: The R package and the supplementary
      documentation are available at http://www.cls.zju.edu.cn/binfo/BNArray/.

PMID- 17005538
TI  - A scalable method for integration and functional analysis of multiple microarray
      datasets.
AB  - MOTIVATION: The diverse microarray datasets that have become available over the
      past several years represent a rich opportunity and challenge for biological data
      mining. Many supervised and unsupervised methods have been developed for the
      analysis of individual microarray datasets. However, integrated analysis of
      multiple datasets can provide a broader insight into genetic regulation of
      specific biological pathways under a variety of conditions. RESULTS: To aid in
      the analysis of such large compendia of microarray experiments, we present
      Microarray Experiment Functional Integration Technology (MEFIT), a scalable
      Bayesian framework for predicting functional relationships from integrated
      microarray datasets. Furthermore, MEFIT predicts these functional relationships
      within the context of specific biological processes. All results are provided in
      the context of one or more specific biological functions, which can be provided
      by a biologist or drawn automatically from catalogs such as the Gene Ontology
      (GO). Using MEFIT, we integrated 40 Saccharomyces cerevisiae microarray datasets
      spanning 712 unique conditions. In tests based on 110 biological functions drawn
      from the GO biological process ontology, MEFIT provided a 5% or greater
      performance increase for 54 functions, with a 5% or more decrease in performance
      in only two functions.

PMID- 17005539
TI  - Electronic personal dosemeters will replace passive dosemeters in the near
      future.

PMID- 17005540
TI  - Neutron dose calculation at the maze entrance of medical linear accelerator
      rooms.
AB  - Currently, teletherapy machines of cobalt and caesium are being replaced by
      linear accelerators. The maximum photon energy in these machines can vary from 4
      to 25 MeV, and one of the great advantages of these equipments is that they do
      not have a radioactive source incorporated. High-energy (E > 10 MV) medical
      linear accelerators offer several physical advantages over lower energy ones: the
      skin dose is lower, the beam is more penetrating, and the scattered dose to
      tissues outside the target volume is smaller. Nevertheless, the contamination of
      undesirable neutrons in the therapeutic beam, generated by the high-energy
      photons, has become an additional problem as long as patient protection and
      occupational doses are concerned. The treatment room walls are shielded to
      attenuate the primary and secondary X-ray fluence, and this shielding is
      generally adequate to attenuate the neutrons. However, these neutrons are
      scattered through the treatment room maze and may result in a radiological
      problem at the door entrance, a high occupancy area in a radiotherapy facility.
      In this article, we used MCNP Monte Carlo simulation to calculate neutron doses
      in the maze of radiotherapy rooms and we suggest an alternative method to the
      Kersey semi-empirical model of neutron dose calculation at the entrance of mazes.
      It was found that this new method fits better measured values found in
      literature, as well as our Monte Carlo simulated ones.

PMID- 17005541
TI  - Incidence and risk factors for urethral and anal gonorrhoea and chlamydia in a
      cohort of HIV-negative homosexual men: the Health in Men Study.
AB  - BACKGROUND: Early detection and treatment of bacterial sexually transmitted
      infections has been advocated as an HIV prevention strategy. AIM: To inform
      screening guidelines, the incidence and risk factors for urethral and anal
      gonorrhoea and chlamydia were studied in a prospective cohort of community-based
      HIV negative homosexual men in Sydney, New South Wales, Australia. METHODS: All
      participants were offered annual screening for gonorrhoea and chlamydia (study
      visit diagnoses) on urine and anal swabs using nucleic acid amplification.
      Participants also reported diagnoses of gonorrhoea and chlamydia made elsewhere
      between interviews (interval diagnoses). All diagnoses were summed to create a
      combined incidence rate, and detailed data on specific sexual practices with
      casual and regular partners were collected. RESULTS: Among 1427 men enrolled, the
      combined incidence rates were 3.49 and 2.96 per 100 person-years for urethral and
      anal gonorrhoea, respectively; and 7.43 and 4.98 per 100 person-years for
      urethral and anal chlamydia, respectively. Urethral infections were associated
      with unprotected anal intercourse (UAI) with HIV-positive partners (hazard ratio
      (HR) = 2.58, 95% CI 1.10 to 6.05 for urethral gonorrhoea) and with frequent
      insertive oral sex (p for trend 0.007 for urethral chlamydia). Anal infections
      were associated with receptive UAI (p for trend 0.001 for both anal gonorrhoea
      and chlamydia) and other receptive anal sexual practices. Stratified analyses
      showed the independence of the associations of insertive oral sex with urethral
      infections and of non-intercourse receptive anal practices with anal infections.
      CONCLUSION: Incident gonorrhoea and chlamydia were common. Risk behaviours for
      both urethral and anal infections were not restricted to UAI. Screening that
      includes tests for anal and urethral infections should be considered for all
      sexually active homosexual men, not just for those who report UAI.

PMID- 17005542
TI  - Why are children still being infected with HIV? Experiences in the prevention of
      mother-to-child transmission of HIV in south London.
AB  - OBJECTIVES: To evaluate the effectiveness of interventions to prevent mother-to
      child transmission of HIV at a large teaching hospital in South East London, and
      to assess reasons for the small numbers of transmissions that continue to occur.
      DESIGN: A database of all pregnant women diagnosed as HIV positive between 1993
      and 2005 was reviewed, with detailed (retrospective) case-note review of all
      mother-infant pairs where HIV transmission occurred. SETTING: King's College
      Hospital, London, UK, a teaching hospital serving an ethnically diverse and
      socially deprived population. RESULTS: 296 pregnancies to 274 women were
      recorded. 9 of 296 (3.0%) women were lost to follow-up before the end of the
      pregnancy. Of 287 pregnancies followed up until after delivery, 6 (2.1%) resulted
      in HIV infection in the infant. More recently, between 2000 and 2004, this
      transmission rate was even lower, at 3 in 231 (1.3%). Each of these six women had
      complications, including late presentation to services and defaulting follow-up
      appointments, which were likely to increase the risk of HIV transmission. Four of
      the six transmissions occurred in utero. CONCLUSION: The overall transmission
      rate of 2% attests to the efforts of the multidisciplinary care team in managing
      this population which is often hard to reach. Clearly, good systems are needed to
      trace those women who default. Further data are needed regarding in utero
      transmissions.

PMID- 17005543
TI  - Immunopathology of intraocular silicone oil: enucleated eyes.
AB  - AIMS: To characterise the distribution of silicone oil in ocular tissues in
      globes enucleated after complicated retinal detachment, and to document the
      distribution and nature of any associated inflammatory response. METHOD: 9
      enucleated globes that had previously undergone retinal detachment surgery with
      silicone oil and 7 control globes that had undergone enucleation after retinal
      detachment surgery (n = 2) or ocular trauma (n = 5) were studied. Sections were
      histologically examined using light microscopy to document the distribution of
      silicone oil in ocular tissues. Immunohistochemical analysis was carried out
      using the ABC technique and a panel of monoclonal and polyclonal antibodies.
      Electron microscopy was undertaken to observe the penetration of silicone oil in
      the trabecular meshwork of the anterior chamber drainage angle. RESULTS: Silicone
      oil was distributed throughout the globes-notably in the iris, ciliary body,
      retina, trabecular meshwork and epiretinal membranes. Focal areas of intraretinal
      silicone were associated with disorganised retinal architecture, retinectomy
      sites or subretinal oil. The distribution of macrophages was closely related to
      the distribution of silicone oil. T and B lymphocytes were not associated with
      silicone oil unless additional pathology was also present-for example, cyclitic
      membrane or uveitis. One of the nine eyes had silicone oil present in the optic
      nerve. In the control globes, the inflammatory response was mediated primarily by
      macrophages and T lymphocytes, and was less marked than that observed in the
      silicone oil globes. CONCLUSION: This study shows that silicone oil may be
      sequestered in varied ocular tissues and is associated with localised
      inflammation mediated by macrophages.

PMID- 17005544
TI  - Immunopathology of intraocular silicone oil: retina and epiretinal membranes.
AB  - AIMS: To determine the inflammatory response in retina and epiretinal membranes
      after intraocular silicone oil tamponade. METHODS: 14 proliferative
      vitreoretinopathy (PVR) epiretinal membranes, 33 retro-oil epiretinal membranes,
      19 retinectomies, 14 retro-oil retinectomies and 37 idiopathic epiretinal
      membranes (controls) underwent immunohistochemical analysis using the avidin
      biotin complex technique and a panel of monoclonal and polyclonal antibodies. The
      number of positive cells counted in five 0.5 mm diameter fields of
      immunohistochemical sections was graded on a score of 1-4. RESULTS: Macrophage
      cell counts were significantly greater in membranes with a history of exposure to
      silicone oil (p<0.001). An inflammatory response could be observed within 1 month
      of silicone oil exchange, and the intensity seemed to be unrelated to the
      duration of exposure. Macrophages were confined to epiretinal membranes on the
      surface of retinectomy specimens in 10 of 14 cases and intraretinal macrophages
      were observed only in specimens with gliotic retina. T and B lymphocytes were
      rarely seen in the specimens examined. Marked glial cell up regulation was
      observed in 11 of 16 retinectomy specimens and in 8 of 11 retro-oil
      retinectomies. Glial cell content was variable in the membranes, but there was a
      trend of increased presence after exposure to silicone oil. CONCLUSION: This
      study has shown that the use of silicone oil is accompanied by an inflammatory
      reaction, primarily mediated by bloodborne macrophages. This response can be
      observed within 1 month of silicone oil injection and continues after silicone
      oil removal. Retinal surgeons should be aware of the potential secondary effects
      of intraocular silicone oil when they are considering its use (and removal) in
      vitreoretinal surgery.

PMID- 17005545
TI  - A "throttle" mechanism in the central retinal vein in the region of the lamina
      cribrosa.
AB  - AIMS: To demonstrate a constriction in the central retinal vein in the region of
      the lamina cribrosa. METHODS: A prospective comparative interventional study of
      13 controls and 19 patients with central retinal vein occlusion (CRVO) using
      colour Doppler imaging of the central retinal artery and vein in the region of
      the lamina cribrosa and optic nerve posterior to the globe. RESULTS: In controls
      peak velocities in the vein were higher in the region of the lamina cribrosa than
      the optic nerve, mean 175 mm/second (mm/s) and 49 mm/s respectively, p<0.0001.
      The velocities in the artery were also higher in the region of the lamina
      cribrosa, mean 122 mm/s and 92 mm/s, p = 0.007. The variability of the velocities
      in the region of the lamina cribrosa was 7.4% in the artery and 15.2% in the
      vein. The mean ratio of the velocities in the vein (4.2 (SD 2.1)) was
      significantly higher than the mean ratio in the artery (1.4 (SD 0.4), p<0.0001).
      In CRVO, the mean ratio in the vein was lower in the affected eyes (2.2 (SD 1.9),
      p<0.01) and fellow unaffected eyes (2.2 (SD 1.0), p = 0.003) than controls. The
      values were stable in eight after radial optic neurotomy. CONCLUSION: The
      presence of a constriction of the vein in the region of the lamina cribrosa can
      be inferred from the presence of higher blood velocities at this site than
      further back in the optic nerve. In CRVO there may be a more uniform narrowing of
      the vein along its course in the nerve. Neurotomy did not affect the
      measurements.

PMID- 17005546
TI  - Neoplastic transformation of ciliary body epithelium is associated with loss of
      opticin expression.
AB  - BACKGROUND: Opticin is a recently discovered glycoprotein present predominantly
      in the vitreous humour. It is synthesised and secreted by the ciliary body
      epithelium (CBE) from the initiation of CBE development in the embryo, and
      production continues throughout life. AIM: To determine whether a variety of
      ciliary body tumours synthesise opticin to characterise further its role in
      ciliary body health and disease. METHODS: Immunohistochemistry was used to
      determine the distribution of opticin in normal human CBE, and in hyperplastic
      and neoplastic CBE lesions. RESULTS: Opticin was immunolocalised to the basal
      cell surface and basement membrane material of the non-pigmented CBE in nine
      donor eyes as well as four hyperplastic lesions of the CBE (Fuchs's adenoma). By
      contrast, none of eight neoplastic lesions (two adenoma and six adenocarcinoma)
      of CBE stained for opticin. CONCLUSION: The present series supports the theory
      that opticin is produced by the non-pigmented CBE throughout adult life. Loss of
      opticin expression by this tissue is associated with and could contribute towards
      neoplastic transformation.

PMID- 17005547
TI  - Pars plana vitrectomy with intravitreal triamcinolone: effect on uveitic cystoid
      macular oedema and treatment limitations.
AB  - OBJECTIVE: To investigate the effect of pars plana vitrectomy (PPV) in
      combination with intraoperative intravitreal triamcinolone acetonide injection on
      the course of cystoid macular oedema (CME) in patients with uveitis. METHODS:
      Patients with uveitis with CME (n = 19) not responding to systemic
      corticosteroids and/or immunosuppression combined with acetazolamide were
      retrospectively studied after PPV with additional intravitreal injection of 4 mg
      triamcinolone acetonide. Patients had chronic anterior uveitis (n = 4),
      intermediate uveitis (n = 9), posterior uveitis (n = 3) or panuveitis (n = 3).
      Visual acuity tests, tonometry, fluorescein angiographic appearance and
      postoperative complications were analysed. Mean follow-up was 14 months (SD 4.6).
      RESULTS: CME improved in 58% of the patients within the first 6 weeks
      postoperatively. After 12 months, CME was further improved in 44% and worsened in
      another 12%. Improvement of visual acuity was noted in 42% after 3 months and in
      28% after 12 months. Cataract progressed in 85% of the phacic patients
      postoperatively. Increased intraocular pressure was detected in 27% at 2 weeks
      and in 11% at 12 months after surgery. CONCLUSION: Uveitic CME that is
      unresponsive to systemic immunosuppression and acetazolamide may improve after
      PPV with additional intravitreal triamcinolone application. The effect seems to
      be transient in many of the patients. Frequent complications were cataract
      formation and ocular hypertension.

PMID- 17005548
TI  - Analysis of bleb morphology after trabeculectomy with Visante anterior segment
      optical coherence tomography.
AB  - BACKGROUND: To describe the use of anterior segment optical coherence tomography
      (OCT) in imaging intrableb morphology after trabeculectomy. METHODS: 14 post
      trabeculectomy eyes from 11 primary open angle glaucoma and 3 primary angle
      closure glaucoma subjects were studied. The blebs were classified with reference
      to slit lamp morphology and bleb function. They included diffuse filtering (n =
      7), cystic (n = 2), encapsulated (n = 2) and flattened (n = 3) bleb types. One
      eye in each patient was imaged with the Visante anterior segment OCT. A vertical
      scan line of 10 mm consisting of 512 A-scans was positioned at the centre of the
      bleb. The images were then analysed by built-in software. Intrableb morphologies
      and structures, including bleb wall thickness, subconjunctival fluid collections,
      suprascleral fluid space, scleral flap thickness, intrableb intensity (low,
      medium or high) and the route under the scleral flap were characterised and
      measured. RESULTS: Diffuse filtering blebs were found by subconjunctival fluid
      collections. Suprascleral fluid space and the route under the scleral flap were
      identified in four of the seven cases. Cystic blebs were composed of a large
      hyporeflective space with multiloculated fluid collections covered by a thin
      layer of conjunctiva. Encapsulated blebs had a thick bleb wall with high
      reflectivity and an enclosed fluid filled space. Flattened blebs demonstrated
      high scleral reflectivity and no bleb elevation. CONCLUSIONS: Visante anterior
      segment OCT can be used for bleb imaging. The different patterns of intrableb
      morphology identified by OCT were related to slit lamp appearance and bleb
      function. This information may be useful to study the different surgical outcomes
      and the process of wound healing in trabeculectomised eyes.

PMID- 17005549
TI  - Efficacy and safety of short duration azithromycin eye drops versus azithromycin
      single oral dose for the treatment of trachoma in children: a randomised,
      controlled, double-masked clinical trial.
AB  - AIMS: Efficacy and safety of a short-duration treatment of azithromycin 1.5% eye
      drops versus oral azithromycin to treat active trachoma. METHODS: Randomised,
      controlled, double-masked, double-dummy, non-inferiority explanatory study
      including 670 children from Guinea Conakry and Pakistan if: 1-10 years old;
      active trachoma (TF+TI0 or TF+TI+ on simplified World Health Organisation (WHO)
      scale). Three groups received either: azithromycin 1.5% eye drops twice daily for
      2 days, for 3 days or azithromycin single 20 mg/kg oral dose. Patients' contacts
      were treated whenever possible. Clinical evaluation was performed using a
      binocular loupe. Primary efficacy variable was the cure (no active trachoma
      (TF0)) at day 60. Non-inferiority margin for difference between cure rates was
      10%. RESULTS: Cure rate in per protocol set was as follows: 93.0%, 96.3% and
      96.6% in 2-day group 3-day group, and oral treatment group, respectively.
      Azithromycin 1.5% groups were non-inferior to oral azithromycin. The intend to
      treat (ITT) analysis supported the results. Clinical re-emergence rate was low:
      4.2%. Ocular tolerance was similar for all groups. No treatment related adverse
      events were reported. Logistic regression analyses found prognostic factors such
      as: country (p<0.001) and trachoma severity (p = 0.003). CONCLUSIONS: In active
      trachoma, azithromycin eye drops twice daily for 2 or 3 days are as efficient as
      the WHO's reference treatment and represent an innovative alternative to oral
      azithromycin.

PMID- 17005550
TI  - Re-solving the cadherin-catenin-actin conundrum.

PMID- 17005551
TI  - The fibroblast growth factor receptor acid box is essential for interactions with
      N-cadherin and all of the major isoforms of neural cell adhesion molecule.
AB  - Interactions between the neural cell adhesion molecules NCAM and N-cadherin with
      the fibroblast growth factor receptor (FGFR) are important for a number of
      developmental events and have also been implicated in tumor progression. The
      factors regulating these interactions are not known. We have used co
      immunoprecipitation and co-clustering paradigms to show that both adhesion
      molecules can interact with the 3Ig IIIC isoform of the FGFR1 in a number of cell
      types. Interestingly, whereas the interaction can be seen over most of the cell
      surface, it is not seen at points of cell-cell contact where the adhesion
      molecules accumulate at stable junctions. We also demonstrate for the first time
      that all of the major isoforms of NCAM can interact with the FGFR. Using deletion
      mutagenesis we have found that the adhesion molecule/FGFR interaction can
      withstand the removal of most of any one of the FGFR immunoglobulin-like domains
      (D1-D3). In contrast, the FGFR interaction with N-cadherin and NCAM (but not FGF)
      is absolutely dependant on the presence of the acid box motif that can be found
      in the linker region between D1 and D2. As this motif can be spliced out of all
      four FGFRs, it suggests that this is one mechanism that can regulate the
      interaction of the receptor with different ligand classes.

PMID- 17005552
TI  - Nonpolar nucleobase analogs illuminate requirements for site-specific DNA
      cleavage by vaccinia topoisomerase.
AB  - Vaccinia DNA topoisomerase forms a covalent DNA-(3'-phosphotyrosyl)-enzyme
      intermediate at a specific target site 5'-C(+5)C(+4)C(+3)T(+2)T(+1)p downward
      arrow N(-1) in duplex DNA. Here we study the effects of nonpolar pyrimidine
      isosteres difluorotoluene (F) and monofluorotoluene (D) and the nonpolar purine
      analog indole at individual positions of the scissile and nonscissile strands on
      the rate of single-turnover DNA transesterification and the cleavage-religation
      equilibrium. Comparison of the effects of nonpolar base substitution to the
      effects of abasic lesions reported previously allowed us to surmise the relative
      contributions of base-stacking and polar edge interactions to the DNA
      transesterification reactions. For example, the deleterious effects of
      eliminating the +2T base on the scissile strand were rectified by introducing the
      nonpolar F isostere, whereas the requirement for the +1T base was not elided by F
      substitution. We impute a role for +1T in recruiting the catalytic residue Lys
      167 to the active site. Topoisomerase is especially sensitive to suppression of
      DNA cleavage upon elimination of the +4G and +3G bases of the nonscissile strand.
      Indole provided little or no gain of function relative to abasic lesions. Inosine
      substitutions for +4G and +3G had no effect on transesterification rate, implying
      that the guanine exocyclic amine is not a critical determinant of DNA cleavage.
      Prior studies of 2-aminopurine and 7-deazaguanine effects had shown that the O6
      and N7 of guanine were also not critical. These findings suggest that either the
      topoisomerase makes functionally redundant contacts with polar atoms (likely via
      Tyr-136, a residue important for precleavage active site assembly) or that it
      relies on contacts to N1 or N3 of the purine ring. The cleavage-religation
      equilibrium is strongly skewed toward trapping of the covalent intermediate by
      elimination of the +1A base of the nonscissile strand; the reaction equilibrium
      is restored by +1 indole, signifying that base stacking flanking the nick is
      critical for the religation step. Our findings highlight base isosteres as
      valuable tools for the analysis of proteins that act on DNA in a site-specific
      manner.

PMID- 17005553
TI  - Incorporation and replication of 8-oxo-deoxyguanosine by the human mitochondrial
      DNA polymerase.
AB  - To assess the role of oxidative stress on the replication of mitochondrial DNA,
      we examined the kinetics of incorporation of 8-oxo-7,8-dihydroguanosine (8-oxodG)
      triphosphate catalyzed by the human mitochondrial DNA polymerase. Using transient
      state kinetic methods, we quantified the kinetics of incorporation, excision, and
      extension beyond a base pair containing 8-oxodG. The 8-oxodGTP was incorporated
      opposite dC in the template with a specificity constant of 0.005 microM(-1) s(
      1), a value approximately 10,000-fold lower than that for dGTP. Once
      incorporated, 96% of the time 8-oxodGMP was extended by continued polymerization
      rather than being excised by the proofreading exonuclease. The specificity
      constant for incorporation of 8-oxodGTP opposite a template dA was 0.2 microM(-1)
      s(-1), a value 13-fold higher than incorporation opposite a template dC. The 8
      oxodG:dA mispair was extended rather than excised at least 70% of the time.
      Examination of the kinetics of polymerization with 8-oxodG in the template strand
      also revealed relatively low fidelity in that dCTP would be incorporated only 90%
      of the time. In nearly 10% of events, dATP would be incorporated, and once
      incorporated dA (opposite 8-oxodG) was extended rather than excised. The greatest
      fidelity was against a dTTP:8-oxodG mismatch affording a discrimination value of
      only 1800. These data reveal that 8-oxodGTP is a potent mutagen. Once it is
      incorporated into DNA, 8-oxodGMP codes for error prone DNA synthesis. These
      reactions are likely to play important roles in oxidative stress in mitochondria
      related to aging and as compounded by nucleoside analogs used to treat human
      immunodeficiency virus infections.

PMID- 17005554
TI  - Fidelity of the human mitochondrial DNA polymerase.
AB  - We have quantified the fidelity of polymerization of DNA by human mitochondrial
      DNA polymerase using synthetic DNA oligonucleotides and recombinant holoenzyme
      and examining each of the possible 16-base pair combinations. Although the
      kinetics of incorporation for all correct nucleotides are similar, with an
      average Kd of 0.8 microM and an average k(pol) of 37 s(-1), the kinetics of
      misincorporation vary widely. The ground state binding Kd of incorrect bases
      ranges from a low of 25 microM for a dATP:A mispair to a high of 360 microM for a
      dCTP:T mispair. Similarly, the rates of incorporation of incorrect bases vary
      from 0.0031 s(-1) for a dCTP:C mispair to 1.16 s(-1) for a dGTP:T mispair. Due to
      the variability in the kinetic parameters for misincorporation, the estimates of
      fidelity range from 1 error in 3563 nucleotides for dGTP:T to 1 error in 2.3 x
      10(6) nucleotides for dCTP:C. Interestingly, the discrimination against a dGTP:T
      mismatch is 16.5 times lower than that of a dTTP:G mismatch due to a tighter Kd
      for ground state binding and a faster rate of incorporation of the dGTP:T
      mismatch relative to the dTTP:G mismatch. We calculate an average fidelity of 1
      error in 440,000 nucleotides.

PMID- 17005555
TI  - The structure of the Lingo-1 ectodomain, a module implicated in central nervous
      system repair inhibition.
AB  - Nogo receptor (NgR)-mediated control of axon growth relies on the central nervous
      system-specific type I transmembrane protein Lingo-1. Interactions between Lingo
      1 and NgR, along with a complementary co-receptor, result in neurite and axonal
      collapse. In addition, the inhibitory role of Lingo-1 is particularly important
      in regulation of oligodendrocyte differentiation and myelination, suggesting that
      pharmacological modulation of Lingo-1 function could be a novel approach for
      nerve repair and remyelination therapies. Here we report on the crystal structure
      of the ligand-binding ectodomain of human Lingo-1 and show it has a bimodular,
      kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)
      like modules. The structure, together with biophysical analysis of its solution
      properties, reveals that in the crystals and in solution Lingo-1 persistently
      associates with itself to form a stable tetramer and that it is its LRR-Ig
      composite fold that drives such assembly. Specifically, in the crystal structure
      protomers of Lingo-1 associate in a ring-shaped tetramer, with each LRR domain
      filling an open cleft in an adjacent protomer. The tetramer buries a large
      surface area (9,200 A2) and may serve as an efficient scaffold to simultaneously
      bind and assemble the NgR complex components during activation on a membrane.
      Potential functional binding sites that can be identified on the ectodomain
      surface, including the site of self-recognition, suggest a model for protein
      assembly on the membrane.

PMID- 17005556
TI  - Autophagy for cancer therapy through inhibition of pro-apoptotic proteins and
      mammalian target of rapamycin signaling.
AB  - Autophagy is an alternative cell death pathway that is induced by mammalian
      target of rapamycin (mTOR) inhibitors and up-regulated when apoptosis is
      defective. We investigated radiation-induced autophagy in the presence or absence
      of Bax/Bak with or without an mTOR inhibitor, Rad001. Two isogenic cell lines,
      wild type (WT) and Bak/Bak(-/-) mouse embryonic fibroblasts and tumor cell lines
      were used for this study. Irradiated Bak/Bak(-/-) cells had a decrease of
      Akt/mTOR signaling and a significant increase of pro-autophagic proteins ATG5
      ATG12 COMPLEX and Beclin-1. These molecular events resulted in an up-regulation
      of autophagy. Bax/Bak(-/-) cells were defective in undergoing apoptosis but were
      more radiosensitive than the WT cells in autophagy. Both autophagy and
      sensitization of Bak/Bax(-/-) cells were further enhanced in the presence of
      Rad001. In contrast, inhibitors of autophagy rendered the Bak/Bax(-/-) cells
      radioresistant, whereas overexpression of ATG5 and Beclin-1 made the WT cells
      radiosensitive. When this novel concept of radiosensitization was tested in
      cancer models, small interfering RNAs against Bak/Bax also led to increased
      autophagy and sensitization of human breast and lung cancer cells to gamma
      radiation, which was further enhanced by Rad001. This is the first report to
      demonstrate that inhibition of pro-apoptotic proteins and induction of autophagy
      sensitizes cancer cells to therapy. Therapeutically targeting this novel pathway
      may yield significant benefits for cancer patients.

PMID- 17005557
TI  - The long alpha-helix of SecA is important for the ATPase coupling of
      translocation.
AB  - SecA contains two ATPase folds (NBF1 and NBF2) and other interaction/regulatory
      domains, all of which are connected by a long helical scaffold domain (HSD)
      running along the molecule. Here we identified a functionally important and
      spatially adjacent pair of SecA residues, Arg-642 on HSD and Glu-400 on NBF1. A
      charge-reversing substitution at either position as well as disulfide tethering
      of these positions inactivated the translocation activity. Interestingly,
      however, the translocation-inactive SecA variants fully retained the ability to
      up-regulate the ATPase in response to a preprotein and the SecYEG translocon. The
      translocation defect was suppressible by second site alterations at the hinge
      forming boundary of NBF2 and HSD. Based on these results, we propose that the
      motor function of SecA is realized by ligand-activated ATPase engine and its HSD
      mediated conversion into the mechanical work of preprotein translocation.

PMID- 17005558
TI  - Small organic compounds enhance antigen loading of class II major
      histocompatibility complex proteins by targeting the polymorphic P1 pocket.
AB  - Major histocompatibility complex (MHC) molecules are a key element of the
      cellular immune response. Encoded by the MHC they are a family of highly
      polymorphic peptide receptors presenting peptide antigens for the surveillance by
      T cells. We have shown that certain organic compounds can amplify immune
      responses by catalyzing the peptide loading of human class II MHC molecules HLA
      DR. Here we show now that they achieve this by interacting with a defined binding
      site of the HLA-DR peptide receptor. Screening of a compound library revealed a
      set of adamantane derivatives that strongly accelerated the peptide loading rate.
      The effect was evident only for an allelic subset and strictly correlated with
      the presence of glycine at the dimorphic position beta86 of the HLA-DR molecule.
      The residue forms the floor of the conserved pocket P1, located in the peptide
      binding site of MHC molecule. Apparently, transient occupation of this pocket by
      the organic compound stabilizes the peptide-receptive conformation permitting
      rapid antigen loading. This interaction appeared restricted to the larger
      Gly(beta86) pocket and allowed striking enhancements of T cell responses for
      antigens presented by these "adamantyl-susceptible" MHC molecules. As catalysts
      of antigen loading, compounds targeting P1 may be useful molecular tools to
      amplify the immune response. The observation, however, that the ligand repertoire
      can be affected through polymorphic sites form the outside may also imply that
      environmental factors could induce allergic or autoimmune reactions in an allele
      selective manner.

PMID- 17005559
TI  - Identification and characterization of a protein-tyrosine phosphatase in
      Leishmania: Involvement in virulence.
AB  - Leishmania parasites are eukaryotic protozoans responsible for a variety of human
      diseases known as leishmaniasis, which ranges from skin lesions to fatal visceral
      infections. Leishmania is transmitted by the bite of an infected sandfly where it
      exists as promastigotes and, upon entry into a mammalian host, differentiates
      into amastigotes, which replicate exclusively in macro-phages. The biochemical
      pathways enabling Leishmania to differentiate and survive in the mammalian host
      are poorly defined. We have therefore examined the role of protein-tyrosine
      phosphorylation, which is essential in regulating cell function in higher
      eukaryotes. Using the recently completed Leishmania genome, we have identified
      and cloned a Leishmania protein-tyrosine phosphatase (PTP) gene (LPTP1) by virtue
      of its homology with the human protein-tyrosine phosphatase 1B gene (hPTP1B). The
      enzyme activity of recombinant LPTP1 was confirmed using a combination of PTP
      specific substrates and inhibitors. We further demonstrate, by creating LPTP1
      null mutants through gene targeting, that LPTP1 is necessary for survival as
      amastigotes in mice, but it is dispensable for survival as promastigotes in
      culture. Human PTPs, including the PTP1B enzyme, are actively pursued drug
      targets for a variety of diseases. The observations with the LPTP1 mutants in
      mice suggest that it may also represent a drug target against the mammalian
      amastigote stage. However, in silico structure analysis of LPTP1 revealed a
      striking similarity with hPTP1B in the active site suggesting that, although this
      is an attractive drug target, it may be difficult to develop an inhibitor
      specific for the Leishmania LPTP1.

PMID- 17005560
TI  - Atomic level insight into the oxidative half-reaction of aromatic amine
      dehydrogenase.
AB  - The quinoprotein aromatic amine dehydrogenase (AADH) uses a covalently bound
      tryptophan tryptophylquinone (TTQ) cofactor to oxidatively deaminate primary
      aromatic amines. Recent crystal structures have provided insight into the
      reductive half-reaction. In contrast, no atomic details are available for the
      oxidative half-reaction. The TTQ O7 hydroxyl group is protonated during
      reduction, but it is unclear how this proton can be removed during the oxidative
      half-reaction. Furthermore, compared with the electron transfer from the N-quinol
      form, electron transfer from the non-physiological O-quinol form to azurin is
      significantly slower. Here we report crystal structures of the O-quinol, N
      quinol, and N-semiquinone forms of AADH. A comparison of oxidized and substrate
      reduced AADH species reveals changes in the TTQ-containing subunit, extending
      from residues in the immediate vicinity of the N-quinol to the putative azurin
      docking site, suggesting a mechanism whereby TTQ redox state influences
      interprotein electron transfer. In contrast, chemical reduction of the TTQ center
      has no significant effect on protein conformation. Furthermore, structural
      reorganization upon substrate reduction places a water molecule near TTQ O7 where
      it can act as proton acceptor. The structure of the N-semiquinone, however, is
      essentially similar to oxidized AADH. Surprisingly, in the presence of substrate
      a covalent N-semiquinone substrate adduct is observed. To our knowledge this is
      the first detailed insight into a complex, branching mechanism of quinone
      oxidation where significant structural reorganization upon reduction of the
      quinone center directly influences formation of the electron transfer complex and
      nature of the electron transfer process.

PMID- 17005561
TI  - A functional transsulfuration pathway in the brain links to glutathione
      homeostasis.
AB  - Oxidative stress and diminished glutathione pools play critical roles in the
      pathogenesis of neurodegenerative diseases, including Alzheimer and Parkinson
      disease. Synthesis of glutathione, the most abundant mammalian antioxidant, is
      regulated at the substrate level by cysteine, which is synthesized from
      homocysteine via the transsulfuration pathway. Elevated homocysteine and
      diminished glutathione levels, seen in Alzheimer and Parkinson disease patients
      suggest impairments in the transsulfuration pathway that connects these
      metabolites. However, the very existence of this metabolic pathway in the brain
      is a subject of controversy. The product of the first of two enzymes in this
      pathway, cystathionine, is present at higher levels in brain as compared with
      other organs. This, together with the reported absence of the second enzyme,
      gamma-cystathionase, has led to the suggestion that the transsulfuration pathway
      is incomplete in the brain. In this study, we incubated mouse and human neurons
      and astrocytes and murine brain slices in medium with [35S]methionine and
      detected radiolabel incorporation into glutathione. This label transfer was
      sensitive to inhibition of gamma-cystathionase. In adult brain slices,
      approximately 40% of the glutathione was depleted within 10 h following gamma
      cystathionase inhibition. In cultured human astrocytes, flux through the
      transsulfuration pathway increased under oxidative stress conditions, and
      blockade of this pathway led to reduced cell viability under oxidizing
      conditions. This study establishes the presence of an intact transsulfuration
      pathway and demonstrates its contribution to glutathione-dependent redox
      buffering capacity under ex vivo conditions in brain cells and slices.

PMID- 17005562
TI  - Centaurin beta1 down-regulates nucleotide-binding oligomerization domains 1- and
      2-dependent NF-kappaB activation.
AB  - Centaurin beta1 (CENTB1), a GTPase-activating protein, is a member of the ADP
      ribosylation factor family encoded by a gene located on the short arm of human
      chromosome 17. A yeast two-hybrid screen first suggested a direct interaction
      between CENTB1 and NOD2. Co-immunoprecipitation experiments confirmed direct
      interaction between CENTB1 and NOD2 and demonstrated similar interaction between
      CENTB1 and NOD1. We also demonstrate that endogenous CENTB1 interacts with
      endogenous NOD2 and NOD1 in SW480 and HT-29 intestinal epithelial cells. CENTB1
      partially co-localized with NOD2 and NOD1 proteins in the cytoplasm of mammalian
      cells. CENTB1 expression in epithelial cells was highly induced by tumor necrosis
      factor alpha, interleukin 1beta, and the NOD1 and NOD2 ligands (gamma-d-glutamyl
      meso-diaminopimelic acid and muramyl dipeptide, respectively). In addition,
      CENTB1 mRNA level is increased in the inflamed mucosa of patients with
      inflammatory bowel disease. Functionally, CENTB1 overexpression inhibited NOD1-
      and NOD2-dependent activation of NF-kappaB, whereas small inhibitory RNA against
      CENTB1 increased NF-kappaB activation following NOD1- or NOD2-mediated
      recognition of the bacterial components gamma-d-glutamyl-meso-diaminopimelic acid
      and muramyl dipeptide, respectively. In contrast, CENTB1 had no effect on NF
      kappaB activation induced by Toll-like receptors. In conclusion, CENTB1
      selectively down-regulates NF-kappaB activation via NODs pathways, creating a
      "feedback" loop and suggesting a novel role of CENTB1 in innate immune responses
      to bacteria and inflammatory responses.

PMID- 17005563
TI  - Phosphatidylinositol 4-phosphate is required for translation initiation in
      Saccharomyces cerevisiae.
AB  - The small natural product wortmannin inhibits protein synthesis by modulating
      several phosphatidylinositol (PI) metabolic pathways. A primary target of
      wortmannin in yeast is the plasma membrane-associated PI 4-kinase (PI4K) Stt4p,
      which is required for actin cytoskeleton organization. Here we show that
      wortmannin treatment or inactivation of Stt4p, but not disorganization of the
      actin cytoskeleton per se, leads to a rapid attenuation of translation
      initiation. Interestingly, inactivation of Pik1p, a wortmannin-insensitive,
      functionally distinct PI4K, implicated in the regulation of Golgi functions and
      secretion, also results in severe translation initiation defects with a marked
      increase of the phosphorylation of the translation initiation factor eIF2alpha.
      Because wortmannin largely phenocopies the effects of rapamycin (e.g. it triggers
      nuclear accumulation of Gln3p), it likely also inhibits the PI kinase-related,
      target of rapamycin (TOR) kinases. Importantly, however, neither inactivation of
      Stt4p nor Pik1p significantly affects TOR-controlled readouts other than
      translation initiation, indicating that these PI4Ks do not simply function
      upstream of TOR. Together, our results reveal the existence of a novel
      translation initiation control mechanism in yeast that is tightly coupled to the
      synthesis of distinct PI4P pools.

PMID- 17005565
TI  - Transient state kinetics of transcription elongation by T7 RNA polymerase.
AB  - The single subunit DNA-dependent RNA polymerase (RNAP) from bacteriophage T7
      catalyzes both promoter-dependent transcription initiation and promoter
      independent elongation. Using a promoter-free substrate, we have dissected the
      kinetic pathway of single nucleotide incorporation during elongation. We show
      that T7 RNAP undergoes a slow conformational change (0.01-0.03 s(-1)) to form an
      elongation competent complex with the promoter-free substrate (dissociation
      constant (Kd) of 96 nM). The complex binds to a correct NTP (Kd of 80 microM) and
      incorporates the nucleoside monophosphate (NMP) into RNA primer very efficiently
      (220 s(-1) at 25 degrees C). An overall free energy change (-5.5 kcal/mol) and
      internal free energy change (-3.7 kcal/mol) of single NMP incorporation was
      calculated from the measured equilibrium constants. In the presence of inorganic
      pyrophosphate (PPi), the elongation complex catalyzes the reverse
      pyrophosphorolysis reaction at a maximum rate of 0.8 s(-1) with PPi Kd of 1.2 mM.
      Several experiments were designed to investigate the rate-limiting step in the
      pathway of single nucleotide addition. Acid-quench and pulse-chase kinetics
      indicated that an isomerization step before chemistry is rate-limiting. The very
      similar rate constants of sequential incorporation of two nucleotides indicated
      that the steps after chemistry are fast. Based on available data, we propose that
      the preinsertion to insertion isomerization of NTP observed in the
      crystallographic studies of T7 RNAP is a likely candidate for the rate-limiting
      step. The studies here provide a kinetic framework to investigate structure
      function and fidelity of RNA synthesis and to further explore the role of the
      conformational change in nucleotide selection during RNA synthesis.

PMID- 17005564
TI  - tBid elicits a conformational alteration in membrane-bound Bcl-2 such that it
      inhibits Bax pore formation.
AB  - During initiation of apoptosis, Bcl-2 family proteins regulate the permeability
      of mitochondrial outer membrane. BH3-only protein, tBid, activates pro-apoptotic
      Bax to release cytochrome c from mitochondria. tBid also activates anti-apoptotic
      Bcl-2 in the mitochondrial outer membrane, changing it from a single-spanning to
      a multispanning conformation that binds the active Bax and inhibits cytochrome c
      release. However, it is not known whether other mitochondrial proteins are
      required to elicit the tBid-induced Bcl-2 conformational alteration. To define
      the minimal components that are required for the functionally important Bcl-2
      conformational alteration, we reconstituted the reaction using purified proteins
      and liposomes. We found that purified tBid was sufficient to induce a
      conformational alteration in the liposome-tethered, but not cytosolic Bcl-2,
      resulting in a multispanning form that is similar to the one found in the
      mitochondrial outer membrane of drug-treated cells. Mutations that abolished
      tBid/Bcl-2 interaction also abolished the conformational alteration,
      demonstrating that a direct tBid/Bcl-2 interaction at the membrane is both
      required and sufficient to elicit the conformational alteration. Furthermore,
      active Bax also elicited the Bcl-2 conformational alteration. Bcl-2 mutants that
      displayed increased or decreased activity in the conformational alteration assay
      showed corresponding activities in inhibiting pore formation by Bax in vitro and
      in preventing apoptosis in vivo. Thus, there is a strong correlation between the
      direct interaction of membrane-bound Bcl-2 and tBid with activation of Bcl-2 in
      vitro and in vivo.

PMID- 17005566
TI  - Hop cleavage and function in granzyme B-induced apoptosis.
AB  - Granzyme B (GzmB) is a cytotoxic protease found in the granules of natural killer
      cells and cytotoxic T lymphocytes. GzmB cleaves multiple intracellular protein
      substrates, leading to caspase activation, DNA fragmentation, cytoskeletal
      instability, and rapid induction of target cell apoptosis. However, no known
      individual substrate is required for GzmB to induce apoptosis. GzmB is therefore
      thought to initiate multiple cell death pathways simultaneously to ensure the
      death of target cells. We previously identified Hop (Hsp70/Hsp90-organizing
      protein) as a GzmB substrate in a proteomic survey (Bredemeyer, A. J., Lewis, R.
      M., Malone, J. P., Davis, A. E., Gross, J., Townsend, R. R., and Ley, T. J.
      (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 11785-11790). Hop is a co-chaperone
      for Hsp70 and Hsp90, which have been implicated in the negative regulation of
      apoptosis. We therefore hypothesized that Hop may have an anti-apoptotic function
      that is abolished upon cleavage, lowering the threshold for GzmB-induced
      apoptosis. Here, we show that Hop was cleaved directly by GzmB in vitro and in
      cells undergoing GzmB-induced apoptosis. Expression of the two cleavage fragments
      of Hop did not induce cell death. Although cleavage of Hop by GzmB destroyed Hop
      function in vitro, both cells overexpressing GzmB-resistant Hop and cells with a
      90-95% reduction in Hop levels exhibited unaltered susceptibility to GzmB-induced
      death. We conclude that Hop per se does not set the threshold for susceptibility
      to GzmB-induced apoptosis. Although it is possible that Hop may be cleaved by
      GzmB as an "innocent bystander" during the induction of apoptosis, it may also
      act to facilitate apoptosis in concert with other GzmB substrates.

PMID- 17005567
TI  - Sugar-derived glasses support thermal and photo-initiated electron transfer
      processes over macroscopic distances.
AB  - Trehalose-derived glasses are shown to support long range electron transfer
      reactions between spatially well separated donors and protein acceptors. The
      results indicate that these matrices can be used not only to greatly stabilize
      protein structures but also to facilitate both thermal and photo-initiated
      hemeprotein reduction over large macroscopic distances. To date the promise of
      exciting new protein-based technologies that can harness the exceptional
      tunability of protein functionality has been significantly thwarted by both
      intrinsic instability and stringent solvent/environment requirements for the
      expression of functional properties. The presented results raise the prospect of
      overcoming these limitations with respect to incorporating redox active proteins
      into solid state devices such as tunable batteries, switches, and solar cells.
      The findings also have implications for formulations intended to enhance long
      term storage of biomaterials, new protein-based synthetic strategies, and
      biophysical studies of functional intermediates trapped under nonequilibrium
      conditions. In addition, the study shows that certain sugars such as glucose or
      tagatose, when added to redox-inactive glassy matrices, can be used as a source
      of thermal electrons that can be harvested by suitable redox active proteins,
      raising the prospect of using common sugars as an electron source in solid state
      thermal fuel cells.

PMID- 17005568
TI  - A novel SET domain methyltransferase in yeast: Rkm2-dependent trimethylation of
      ribosomal protein L12ab at lysine 10.
AB  - The ribosomal protein L12ab (Rpl12ab) in Saccharomyces cerevisiae is modified by
      methylation at both arginine and lysine residues. Although the enzyme responsible
      for the modification reaction at arginine 66 has been identified (Rmt2), the
      enzyme(s) responsible for the lysine modification(s) has not been found, and the
      site(s) of methylation has not been determined. Here we demonstrate, using a
      combination of mass spectrometry and labeling assays, that the yeast gene YDR198c
      encodes the enzyme responsible for the predominant epsilon-trimethylation at
      lysine 10 in Rpl12ab. An additional site of predominant epsilon-dimethylation is
      observed at lysine 3; the enzyme catalyzing this modification is not known. The
      YDR198c gene encodes a SET domain similar to that of the Rkm1 enzyme responsible
      for modifying Rpl23ab, and we have now designated the YDR198c gene product as
      Rkm2 (ribosomal lysine methyltransferase 2). The effect of the loss of the enzyme
      on ribosomal complex stability was studied by polysomal fractionation. However,
      no difference was observed between the Deltarkm2 deletion strain and its parent
      wild type strain. With the identification of this enzyme, it appears that the 12
      SET domain family members in yeast can now be divided into two subfamilies based
      on function and amino acid sequence identity. One branch includes enzymes that
      modify histones, including Set1 and Set2; the other branch includes Rkm1, Rkm2,
      and Ctm1, the cytochrome c methyltransferase. These studies suggest that the
      remaining seven SET domain proteins may also be lysine methyltransferases.

PMID- 17005569
TI  - The duck hepatitis B virus reverse transcriptase functions as a full-length
      monomer.
AB  - Hepadnaviral reverse transcription occurs within cytoplasmic capsid particles and
      is catalyzed by a virally encoded reverse transcriptase, but the primary
      structure and multimeric state of the polymerase during reverse transcription are
      poorly understood. We measured these parameters for the duck hepatitis B virus
      polymerase employing active enzyme translated in vitro and derived from
      intracellular core particles and mature virions. In vitro-translated polymerase
      immunoprecipitated as a monomer, and polymerase molecules with complementary
      defects in the enzymatic active site and tyrosine 96, which primes DNA synthesis,
      could not complement or inhibit each other in priming assays. Western analysis
      using antibodies recognizing epitopes throughout the polymerase combined with
      nuclease digestion of permeabilized virion-derived capsid particles revealed that
      only full-length polymerase molecules were in virions and that they were all
      covalently attached to large DNA molecules. Because DNA synthesis is primed by
      the polymerase itself and only one copy of the viral DNA is in each capsid, the
      polymerase must function as an uncleaved monomer. Therefore, a single polymerase
      monomer is encapsidated, primes DNA synthesis, synthesizes both DNA strands, and
      participates in the three-strand transfers of DNA synthesis, with all steps after
      DNA priming performed while the polymerase is covalently coupled to the product
      DNA. Because the N-terminal domain of the polymerase is displaced from the active
      site on the same molecule by the viral DNA during reverse transcription, P must
      be structurally dynamic during DNA synthesis. Therefore, non-nucleoside compounds
      that interfere with this change may be novel antiviral agents.

PMID- 17005570
TI  - The Smc5-Smc6 DNA repair complex. bridging of the Smc5-Smc6 heads by the KLEISIN,
      Nse4, and non-Kleisin subunits.
AB  - Structural maintenance of chromosomes (SMC) proteins play fundamental roles in
      many aspects of chromosome organization and dynamics. The SMC complexes form
      unique structures with long coiled-coil arms folded at a hinge domain, so that
      the globular N- and C-terminal domains are brought together to form a "head."
      Within the Smc5-Smc6 complex, we previously identified two subcomplexes
      containing Smc6-Smc5-Nse2 and Nse1-Nse3-Nse4. A third subcomplex containing Nse5
      and -6 has also been identified recently. We present evidence that Nse4 is the
      kleisin component of the complex, which bridges the heads of Smc5 and -6. The C
      terminal part of Nse4 interacts with the head domain of Smc5, and structural
      predictions for Nse4 proteins suggest similar motifs that are shared within the
      kleisin family. Specific mutations within a predicted winged helix motif of Nse4
      destroy the interaction with Smc5. We propose that Nse4 and its orthologs form
      the delta-kleisin subfamily. We further show that Nse3, as well as Nse5 and Nse6,
      also bridge the heads of Smc5 and -6. The Nse1-Nse3-Nse4 and Nse5-Nse6
      subcomplexes bind to the Smc5-Smc6 heads domain at different sites.

PMID- 17005571
TI  - Observing an induced-fit mechanism during sequence-specific DNA methylation.
AB  - The characterization of conformational changes that drive induced-fit mechanisms
      and their quantitative importance to enzyme specificity are essential for a full
      understanding of enzyme function. Here, we report on M.HhaI, a sequence-specific
      DNA cytosine C(5) methyltransferase that reorganizes a flexible loop (residues 80
      100) upon binding cognate DNA as part of an induced-fit mechanism. To directly
      observe this approximately 26A conformational rearrangement and provide a basis
      for understanding its importance to specificity, we replaced loop residues Lys-91
      and Glu-94 with tryptophans. The double mutants W41F/K91W and W41F/E94W are
      relatively unperturbed in kinetic and thermodynamic properties. W41F/E94W shows
      DNA sequence-dependent changes in fluorescence: significant changes in
      equilibrium and transient state fluorescence that occur when the enzyme binds
      cognate DNA are absent with nonspecific DNA. These real-time, solution-based
      results provide direct evidence that binding to cognate DNA induces loop
      reorganization into the closed conformer, resulting in the correct assembly of
      the active site. We propose that M.HhaI scans nonspecific DNA in the loop-open
      conformer and rearranges to the closed form once the cognate site is recognized.
      The fluorescence data exclude mechanisms in which loop motion precedes base
      flipping, and we show loop rearrangements are directly coupled to base flipping,
      because the sequential removal of single hydrogen bonds within the target
      guanosine:cytosine base pair results in corresponding changes in loop motion.

PMID- 17005572
TI  - Kinetic effect of a downstream strand and its 5'-terminal moieties on single
      nucleotide gap-filling synthesis catalyzed by human DNA polymerase lambda.
AB  - During short-patch base excision repair, the excision of a 5'-terminal 2
      deoxyribose-5-phosphate moiety of the downstream strand by the 5'-2-deoxyribose-5
      phosphate lyase activity of either DNA polymerase beta or lambda is believed to
      occur after each respective enzyme catalyzes gap-filling DNA synthesis. Yet the
      effects of this 5'-terminal 2-deoxyribose-5-phosphate moiety on the polymerase
      activities of these two enzymes have never been quantitatively determined.
      Moreover, x-ray crystal structures of truncated polymerase lambda have revealed
      that the downstream strand and its 5'-phosphate group of gapped DNA interact
      intensely with the dRPase domain, but the kinetic effect of these interactions is
      unclear. Here, we utilized pre-steady state kinetic methods to systematically
      investigate the effect of a downstream strand and its 5'-moieties on the
      polymerase activity of the full-length human polymerase lambda. The downstream
      strand and its 5'-phosphate were both found to increase nucleotide incorporation
      efficiency (kp/Kd) by 15 and 11-fold, respectively, with the increase procured by
      the effect on the nucleotide incorporation rate constant kp rather than the
      ground state nucleotide binding affinity Kd. With 4 single nucleotide-gapped DNA
      substrates containing a 1,2-dideoxyribose-5-phosphate moiety, a 2-deoxyribose-5
      phosphate mimic, we measured the incorporation efficiencies of 16 possible
      nucleotides. Our results demonstrate that although this 5'-terminal 2-deoxyribose
      5-phosphate mimic does not affect the fidelity of polymerase lambda, it
      moderately decreased the polymerase efficiency by 3.4-fold. Moreover, this
      decrease in polymerase efficiency is due to a drop of similar magnitude in kp
      rather than Kd. The implication of the downstream strand and its 5'-moieties on
      the kinetics of gap-filling synthesis is discussed.

PMID- 17005573
TI  - Sarcoidosis and MIF gene polymorphism: a case-control study in an Irish
      population.
AB  - Macrophage migration inhibitory factor is a key pro-inflammatory mediator. A 5
      CATT repeat functional polymorphism within the promoter of the gene was
      previously associated with the lowest promoter activity. It was hypothesised that
      patients exhibiting a 5-CATT allele would have a less aggressive inflammatory
      response with an associated less severe clinical phenotype in sarcoidosis. Irish
      Caucasian sarcoidosis patients (n = 173) followed up for 1-39 yrs and a control
      group (n = 166) were genotyped for the CATT repeat polymorphism. Disease severity
      at the time of diagnosis and at the time of elaboration of the present study was
      assessed by the presence of thoracic and extrathoracic symptoms, erythema
      nodosum, radiographic interstitial changes (chest radiograph score equal to stage
      II or greater, or high-resolution computed tomography confirmed), pulmonary
      function tests, steroid use, erythrocyte sedimentation rate, C-reactive protein
      and angiotensin-converting enzyme levels. In the Irish population studied, no
      evidence was found of a significant association between either sarcoidosis
      susceptibility and disease severity and the 5-CATT repeat functional polymorphism
      in the macrophage migration inhibitory gene. The present study found no
      significant association between the 5-CATT repeat macrophage migration inhibitory
      factor gene polymorphism and sarcoidosis, and did not support the overriding role
      for macrophage migration inhibitory factor in driving sarcoidosis pathogenesis.

PMID- 17005574
TI  - Inhibitory effects of repeated hyperoxia on breathing in newborn mice.
AB  - Brief oxygen therapy is commonly used for resuscitation at birth or prevention of
      hypoxaemia before procedures during the neonatal period. However, O(2) may
      severely depress breathing, especially when administered repeatedly. The aim of
      the present study was to test the effects of repeated hyperoxia on breathing
      control in newborn mice. A total of 97 Swiss mouse pups were assigned to O(2) or
      air on post-natal day 0, 1 or 2. Each pup in the O(2) group was subjected to four
      hyperoxic tests (100% O(2) for 3 min followed by 12 min normoxia), whereas pups
      in the air group were maintained in normoxia. Breathing variables were measured
      using flow-through barometric plethysmography. O(2) significantly decreased
      minute ventilation as seen in a decrease in respiratory rate. This decrease
      became significantly larger with repeated exposure and ranged -17- -26% for all
      ages combined. Furthermore, hyperoxia increased total apnoea duration, as
      compared with the baseline value. In newborn mice, repeated hyperoxia
      increasingly depressed breathing. This finding further supports a need for
      stringent control of oxygen therapy, most notably repeated oxygen administration
      in the neonatal period for premature newborn infants and those carried to term.

PMID- 17005575
TI  - Standard anti-tuberculosis treatment and hepatotoxicity: do dosing schedules
      matter?
AB  - A nested case-control study was conducted in order to examine whether dosing
      schedules of standard pyrazinamide-containing anti-tuberculosis (TB) treatment
      (standard treatment) might affect hepatotoxicity. The present authors
      retrospectively identified all patients with hepatitis using biochemical criteria
      from a cohort of 3,007 clinic patients who commenced anti-TB treatment from
      January 1 to June 30, 2001. Each case with hepatitis between 1-9 weeks post-TB
      treatment was compared using conditional logistic regression analysis with two
      controls selected randomly from patients without hepatitis in the same period and
      matched by sex, age and standard treatment. Impacts of sex and age were examined
      by logistic regression analysis of cases and patients without hepatitis.
      Hepatitis occurred in 167 patients, of whom 96 qualified as cases. A conditional
      logistic risk model identified hepatitis B surface antigen carriage as the only
      risk factor (odds ratio (95% confidence interval (CI)) 1.8 (1.1-3.1)). Logistic
      regression analysis showed that sex was nonsignificant but ageing increased the
      odds of hepatitis. The risk of hepatitis increased from 2.6% (1.9-3.5%) to 4.1%
      (3.2-5.3%) as age exceeded 49 yrs. Dosing schedules in the first 9 weeks have
      little impact on hepatotoxicity. If patients at risk of both hepatitis and
      relapse receive standard treatment, daily dosing is preferable.

PMID- 17005576
TI  - Sporadic and epidemic community legionellosis: two faces of the same illness.
AB  - The present study compares the risk factors, presentation and outcome of
      community-acquired Legionella pneumophila pneumonia in 138 sporadic-case patients
      (1994-2004) and 113 outbreak-case patients (2002) treated in two hospitals in
      Catalonia (Spain) since urinary antigen assays were adopted. Univariate and
      multivariate analysis were performed to compare epidemiological and clinical
      features, blood chemistry values, radiological findings and outcome of sporadic
      and epidemic legionnaires' disease. Univariate analysis showed that male sex,
      chronic lung disease, HIV infection and immunosuppressive therapy prevailed in
      sporadic cases. Presentation with respiratory symptoms, confusion and blood
      chemistry alterations, such as hyponatraemia, aspartate aminotransferase and
      blood urea nitrogen elevation, and partial pressure of oxygen P(O)(2) <7.98 KPa
      (60 mmHg) were also more frequent in sporadic cases, while headache prevailed in
      outbreak cases. Sporadic cases had a greater delay in treatment, were more severe
      and had a worse outcome than epidemic cases. Multivariate analysis showed
      significant differences in sex, chronic lung disease, HIV infection and headache.
      The clinical and outcome differences between the two groups may be explained by
      the detection of milder forms of legionnaires' disease, the earlier treatment and
      the lower severity of underlying disease in the outbreak cases.

PMID- 17005577
TI  - Hot biopsy forceps in the diagnosis of endobronchial lesions.
AB  - Electrocoagulation bronchoscopy biopsy forceps may prevent bleeding, but could
      also impair the quality of the specimens obtained. Patients with endobronchial
      lesions during bronchoscopy underwent six endobronchial biopsies each with a hot
      biopsy forceps, alternating between with electrocoagulation ("hot") and without
      ("cold"). Bleeding was quantified on a scale of 1-4, with 1 being no bleeding.
      The generator was set on "soft coagulation" mode, with power settings of 40, 60,
      80 and 100 W for each group of 10 patients in a sequential fashion. Clinical
      pathology results were recorded before samples were reviewed by a second,
      blinded, pulmonary pathologist. A total of 39 patients with 40 endobronchial
      lesions had six biopsies performed (one patient had only four samples taken),
      giving a total of 238 biopsy samples. Concordance between hot and cold samples
      was 92.5% for the clinical pathologist and 87% for the blinded pathologist.
      Paired analysis suggested lower average bleeding score with the use of hot
      forceps. Overall bleeding rates for cold and hot biopsies, respectively, were as
      follows: grade 1: 30.3 and 41.2%; grade 2: 62.2 and 49.6%; grade 3: 7.6 and 9.2%;
      and grade 4: 0 and 0%. In conclusion, the use of hot biopsy forceps for
      endobronchial biopsy does not appear to have a negative impact on the
      pathological samples. Hot biopsy forceps showed a statistically significant
      reduction in bleeding score, which is unlikely to be of clinical significance.

PMID- 17005578
TI  - Obstructive sleep apnoea and oral breathing in patients free of nasal
      obstruction.
AB  - Although there is an association between nasal obstruction, oral breathing and
      obstructive sleep apnoea syndrome (OSAS), it remains unknown whether increased
      oral breathing occurs in patients with OSAS who are free of nasal obstruction.
      The present study evaluated the relationship between breathing route and OSAS in
      patients without nasal obstruction. The breathing route of 41 snorers (25 male;
      aged 26-77 yrs) with normal nasal resistance was examined during overnight
      polysomnography using a nasal cannula/pressure transducer and an oral thermistor.
      In total, 28 patients had OSAS (apnoeics) and 13 patients were simple snorers.
      Apnoeics had a higher percentage of oral and oro-nasal breathing epochs. Oral and
      oro-nasal breathing epochs were positively related with apnoea/hypopnoea index
      (AHI) and duration of apnoeas/hypopnoeas and inversely related to oxygen
      saturation. Additionally, oro-nasal breathing epochs correlated with body mass
      index (BMI). In multiple linear regression analysis, oral breathing epochs were
      independently related only to AHI (r2 = 0.443), and oro-nasal breathing epochs
      were independently related to AHI (r2 = 0.736) and BMI (r2 = 0.036). In
      conclusion, apnoeics spent more time breathing orally and oro-nasally than simple
      snorers, and the apnoea/hypopnoea index is a major determinant of the time spent
      breathing orally and oro-nasally.

PMID- 17005579
TI  - Transbronchial needle aspirates: how many passes per target site?
AB  - Transbronchial needle aspiration is a bronchoscopic sampling method for a variety
      of bronchial and pulmonary lesions. The present study investigated whether and
      how serial needle passes contribute to the yield of transbronchial needle
      aspiration at specific target sites. A total of 1,562 needle passes, performed at
      374 target sites in 245 patients with neoplastic disease (82%), non-neoplastic
      disease (15%) or undiagnosed lesions (3%), were prospectively recorded and rated
      for anatomical location, size, bronchoscopic appearance and underlying disease.
      Positive aspirates were obtained in 75% of patients and at 68% of target sites. A
      diagnosis was established with the first, second, third and fourth needle pass at
      64, 87, 95 and 98% of targets, respectively. The absolute yield varied strongly
      with target site features, but the stepwise increment to the maximum yield
      provided by serial passes was similar across target sites. In conclusion, three
      transbronchial needle passes per site are appropriate when only a tissue
      diagnosis is sought and when alternative sites or sampling modalities are
      available. At least four or five passes should be carried out at lymph node
      stations critical for the staging of lung cancer.

PMID- 17005580
TI  - Economic evaluation of adherence to treatment guidelines in nonintensive care
      pneumonia.
AB  - Guidelines have been developed to improve the treatment of community-acquired
      pneumonia (CAP) but information regarding their influence on costs is lacking.
      The aim of the present study was to conduct a cost-effectiveness analysis of CAP
      treatment from the hospital perspective when adhering to Spanish guidelines. A
      prospective cohort study was performed in 271 patients with CAP admitted to a
      tertiary-care hospital, not needing intensive care. Collected data included
      patients' characteristics, comorbidity, initial risk class, resource use
      (medication, blood and microbiological analyses, and radiology) and economic
      data. Antimicrobial treatment was recorded as adherent or nonadherent to Spanish
      guidelines. Outcome measures were mortality and readmission at 30 days. The
      median cost for adherent treatment was 1,665.5 versus 1,710.5 Euros for
      nonadherent treatment. Mortality and readmission were 10% and 2.1% for adherent
      treatment versus 13.6% and 6.2% for nonadherent treatment. The cost-effectiveness
      ratio was 2,277 Euros per expected cure for patients treated according to the
      guidelines and 2,567 Euros per expected cure for the nonadherence group. The
      incremental cost-effectiveness ratio showed that adherence to treatment
      guidelines saved 1,121 Euros per patient cured compared with nonadherence. The
      sensitivity analysis demonstrated that the findings were robust. An antimicrobial
      treatment according to guidelines is the dominant alternative due to its cost
      effectiveness.

PMID- 17005581
TI  - Spacer inhalation technique and deposition of extrafine aerosol in asthmatic
      children.
AB  - The aim of the present study was to measure airway, oropharyngeal and
      gastrointestinal deposition of (99m)Tc-labelled hydrofluoroalkane-beclomethasone
      dipropionate after inhalation via a pressurised metered-dose inhaler and spacer
      (Aerochamber Plus) in asthmatic children. A group of 24 children (aged 5-17 yrs)
      with mild asthma inhaled the labelled drug. A total of 12 children took five
      tidal breaths after each actuation (tidal group). The other 12 children used a
      slow maximal inhalation followed by a 5 - 10-s breath-hold (breath-hold group).
      Simultaneous anterior and posterior planar gamma-scintigraphic scans (120-s
      acquisition) were recorded. For the tidal group, mean+/-sd lung deposition (% ex
      actuator, attenuation corrected) was 35.4+/-18.3, 47.5+/-13.0 and 54.9+/-11.2 in
      patients aged 5-7 (n = 4), 8-10 (n = 4) and 11-17 yrs (n = 4), respectively.
      Oropharyngeal and gastrointestinal deposition was 24.0+/-10.5, 10.3+/-4.4 and
      10.1+/-6.2. With the breath-hold technique, lung deposition was 58.1+/-6.7,
      56.6+/-5.2 and 58.4+/-9.2. Oropharyngeal and gastrointestinal deposition was
      12.9+/-3.2, 20.1+/-9.5 and 20.8+/-8.8. Inhalation of the extrafine formulation
      with the breath-hold technique showed significantly improved lung deposition
      compared with tidal breathing across all ages. Oropharyngeal and gastrointestinal
      deposition was markedly decreased, regardless of which inhalation technique was
      applied, compared with a previous paediatric study using the same formulation
      delivered via a breath-actuated metered-dose inhaler.

PMID- 17005582
TI  - Gefitinib monotherapy in advanced nonsmall cell lung cancer: a large Western
      community implementation study.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitors represent a new
      treatment option for patients with advanced nonsmall cell lung cancer (NSCLC).
      This retrospective study examined to what extent previous clinical trial
      experience matches large-scale Western community implementation of this
      treatment. In the Belgian expanded access programme, the data from 513 patients
      with advanced or metastatic NSCLC, not suitable for further chemotherapy and
      receiving oral gefitinib 250 mg.day(-1) until disease progression, death or
      unacceptable toxicity, were analysed. The median (range) duration of gefitinib
      treatment was 2.3 months (0.0-32.7). Its use was predominantly in second- or
      third-line treatment. The overall response and disease control rates were 8.9 and
      41.2%, respectively. In univariate analysis, response was more common in females
      and never-smokers. In multivariate analysis, female sex was the only significant
      predictive factor (odds ratio (OR) (95% confidence interval (CI)) 0.329 (0.129
      0.839)). Symptom improvement was reported in 108 patients of whom 32 (29.6%) had
      an objective response, 66 (61.1%) experienced disease stabilisation and 10 (9.3%)
      progressed. Gefitinib was well tolerated; only 7.8% of the patients reported
      grade 3 or 4 toxicity. The overall median survival was 4.7 months, with a 1-yr
      survival rate of 21%. Survival was strongly influenced by a better performance
      status (PS) (good PS: hazard ratio (HR) (95%CI) 0.110 (0.077-0.157)) and
      adenocarcinoma with bronchioloalveolar carcinoma features histology (HR (95%CI)
      0.483 (0.279-0.834)). In conclusion, the activity of gefitinib was confirmed in
      the present large Western community implementation study. Response, present in a
      small subgroup, led to a rewarding survival and could be predicted by sex only.
      Baseline performance status and adenocarcinoma with bronchioloalveolar carcinoma
      features histology were significant factors for survival.

PMID- 17005583
TI  - Utility of exhaled nitric oxide as a noninvasive biomarker of lung inflammation
      in a disease model.
AB  - There is a great deal of interest in developing less invasive markers for
      monitoring airway inflammation and the effect of possible novel anti-inflammatory
      therapies that may take time to impact on disease pathology. Exhaled nitric oxide
      (eNO) has been shown to be a reproducible, noninvasive indicator of the
      inflammatory status of the airway in the clinic. The aim of the present study was
      to determine the usefulness of measuring eNO as a marker of the anti-inflammatory
      impact of glucocorticoid and an inhibitor of kappaB kinase-2 (IKK-2) inhibitor 2
      [(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), in a
      pre-clinical model of airway inflammation. Rats were given vehicle, budesonide or
      TPCA-1 prior to exposure to lipopolysaccharide, previously shown to induce an
      increase in eNO and airway neutrophilia/eosinophilia. Comparison of the effect of
      the two compounds on inflammatory components demonstrated a significant
      correlation between the impact on eNO and inflammatory cell burden in the airway.
      The current study demonstrates the usefulness of profiling potential disease
      modifying therapies on exhaled nitric oxide levels and the way in which an effect
      on this noninvasive biomarker relates to effects on pathological parameters such
      as lung cellularity. Information from studies such as the current one would
      suggest that the measurement of exhaled nitric oxide has potential for monitoring
      inflammatory status in lung tissue.

PMID- 17005584
TI  - The influence of patent foramen ovale on oxygen desaturation in obstructive sleep
      apnoea.
AB  - Obstructive sleep apnoea (OSA) is associated with oxygen desaturation to a
      varying degree. A patent foramen ovale (PFO) may allow interatrial right-to-left
      shunting. The hypothesis of the current study was that oxygen desaturation will
      occur more often, in proportion to the frequency of respiratory disturbances, in
      OSA subjects with PFO than in those without. In a group of 209 subjects diagnosed
      with OSA, the proportion of desaturation to respiratory events was calculated as
      the ratio of oxygen desaturation index (ODI)/apnoea-hypopnoea index (AHI). A
      total of 15 cases with high proportional desaturation (ODI/AHI >or=0.66) were
      individually matched with 15 controls with low proportional desaturation (ODI/AHI
      <or=0.33), all without pulmonary disease. PFO was assessed with contrast
      transoesophageal echocardiography and considered large when >or=20 bubbles passed
      over from the right to the left atrium after a single injection. The prevalence
      of large PFO was nine out of 15 (60%) in the high proportional desaturation group
      versus two out of 15 (13%) in the low proportional desaturation group. The median
      number of passing bubbles was positively correlated to minimum oxygen saturation
      among those with PFO. In conclusion, oxygen desaturation occurs more often, in
      proportion to the frequency of respiratory disturbances, in obstructive sleep
      apnoea subjects with a patent foramen ovale than in those without.

PMID- 17005585
TI  - Surfactant protein C mutations in sporadic forms of idiopathic interstitial
      pneumonias.
AB  - Interstitial pneumonias have recently been associated with mutations in the gene
      encoding surfactant protein C (SFTPC). In particular, SFTPC mutations have been
      reported in a number of familial forms of pulmonary fibrosis and in infants with
      interstitial lung diseases. The present study searched for SFTPC mutations in
      adult patients with sporadic idiopathic interstitial pneumonia. In total, 35
      adult patients with sporadic idiopathic interstitial pneumonia and 50 healthy
      subjects were investigated for SFTPC mutations by direct DNA sequencing. Of the
      patients with sporadic idiopathic interstitial pneumonia, 25 suffered from
      idiopathic pulmonary fibrosis and 10 patients from nonspecific interstitial
      pneumonia. Only two frequent nonsynonymous variants, T138N and S186N, were
      detected. Allele frequencies of both variations as well as of other identified
      noncoding alterations did not differ significantly between the diverse patient
      groups and control subjects. In conclusion, mutations in the gene encoding
      surfactant protein C are not common in sporadic cases of idiopathic pulmonary
      fibrosis and nonspecific interstitial pneumonia, suggesting that the mutated gene
      does not play an important role in the pathogenesis of these forms of idiopathic
      interstitial pneumonia.

PMID- 17005586
TI  - Estimated numbers and prevalence of PI*S and PI*Z deficiency alleles of alpha1
      antitrypsin deficiency in Asia.
AB  - The current study focuses on updating estimates of the numbers of individuals
      carrying the two most common deficiency alleles, protease inhibitor (PI)*S and
      PI*Z, for alpha1-antitrypsin deficiency (AT-D) in 20 Asian countries. A total of
      170 cohorts with 31,177 individuals were selected from 20 Asian countries. The
      total AT-D populations in the countries selected were: 7,264 ZZ; 36,754 SZ;
      6,672,479 MZ; 46,492 SS; and 16,881,108 MS. Marked differences among the Asian
      countries and regions were also found for the prevalence of the deficiency
      alleles PI*S and PI*Z. These numbers demonstrate that AT-D is not just a genetic
      disease that affects smaller numbers than various countries, for example, in
      Europe. There were marked differences between the prevalence of the PI*S and PI*Z
      deficiency alleles among these 20 Asian countries as well as among the countries
      within a given geographic region in Asia. The largest numbers of ZZ phenotypes
      (3,000-14,000) were in Afghanistan, Pakistan, Saudi Arabia and Thailand; with
      <1,700 in each of the remaining countries.

PMID- 17005587
TI  - Expression of histo-blood group antigens in bronchial squamous metaplasia.
AB  - The aim of the present study was to evaluate the expression of blood group
      antigens in squamous bronchial metaplasia in order to determine whether this
      factor could identify patients at risk of lung cancer. In total, 100 bronchial
      biopsies were included in the present study. The cases were classified according
      to the World Health Organization grading system. Immunohistochemical stains for
      histo-blood groups A and B, and reactivity tests to p53 and the cellular
      proliferation index were performed. A total of 56 (56%) patients belonged to
      blood group A. Among them, six (10.7%) patients who did not express antigen in
      squamous metaplasia, showed carcinoma at the moment of the biopsy (n = 3) or
      developed synchronous lung carcinoma (n = 3). A total of nine (9%) patients
      belonged to blood group B. Loss of antigenic expression was observed in five
      cases. All of them developed synchronous lung carcinoma. The patients with low-
      and high-grade dysplasia developed lung cancer in 71 and 100% of the cases,
      respectively. In conclusion, the findings of the present study suggest that the
      loss of histo-blood antigens expression is an event in the carcinogenesis of
      bronchial mucosa and it is usually associated with high-grade lesions and
      hyperproliferative activity.

PMID- 17005588
TI  - Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma.
AB  - The present study aimed to determine the alterations of antioxidant activities in
      erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC). A
      comparative study of the systemic antioxidant activities in red blood cell lysate
      from subjects with NSCLC and healthy control subjects was conducted. The
      antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase
      (GPx) were measured using chemical kinetic reactions under spectrophotometry. In
      total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy
      controls were studied. In subjects with lung cancer, there was similar catalase
      activity, lower SOD activity (median (interquartile range) 13.4 (9.0-27.2) versus
      48.7 (27.0-64.3) U x (ghaemoglobulin(Hb)(-1)), and higher GPx activity (175.2
      (126.6-288.3) versus 49.2 (39.5-59.2) mU x (gHb)(-1)) compared with controls. The
      antioxidant activities in lung cancer subjects were not associated with age, sex,
      smoking status, or tumour cell types. However, more advanced disease (stage IV
      compared with stage IIIB) was associated with lower SOD activity. Using
      multivariable analysis, the presence of lung cancer independently predicted SOD
      and GPx activities. In conclusion, nonsmall cell lung carcinoma in Chinese
      subjects is associated with alterations in systemic antioxidant activities, which
      may play an important role in carcinogenesis.

PMID- 17005589
TI  - A method for the simultaneous analysis of mRNA levels of multiple cardiac ion
      channels with a multi-probe RNase protection assay.
AB  - AIMS: Various pathological conditions can alter cardiac electrophysiological
      properties not only by physiological responses but also by modifying the gene
      expression of ion channels (electrical remodelling). To investigate the
      underlying mechanisms of the latter, electrophysiological alterations would
      require a simultaneous and comprehensive analysis of the mRNA level of the ion
      channel genes. METHODS AND RESULTS: We designed 19 cardiac ion channel cDNA
      templates to analyse the corresponding mRNAs and classified them into three
      template sets. Those sets were a voltage-dependent K(+) channel series (rat erg,
      KvLQT1, Kv4.3, Kv4.2, Kv2.1, Kv1.5, Kv1.4, Kv1.2), an inwardly rectifying K(+)
      channel series (rat Kir6.2, SUR2A/B, Kir3.4, Kir3.1, Kir2.2, Kir2.1), and an
      inward cationic ion channel series (rat SCN5A, alpha1C, beta2, alpha2delta2 of
      cardiac L-type Ca(2+) channel and alpha1G). These cDNA templates were used to
      synthesize antisense digoxigenin-labelled RNA probes. An amount of the total RNA
      of 25 microg was adequate to analyse simultaneously the mRNA levels of the ion
      channel genes with the use of multi-probe RPA, and these three multi-probe
      template sets enabled us to evaluate the profile of the spatial and temporal
      transcripts of the cardiac ion channels. CONCLUSION: The newly developed ion
      channel multi-probe RPA templates provide an aid in the comprehensive analysis of
      the electrical remodelling of the heart.

PMID- 17005590
TI  - Ectopic nodal structures in a patient with atrial tachycardia originating from
      the mitral valve annulus.
AB  - We report a case, which we believe to be rare, of adenosine-sensitive atrial
      tachycardia (AT) originating from the mitral valve annulus. The patient, a 73
      year-old woman, died of unrelated cause 4 years after radiofrequency (RF)
      ablation therapy. Histologically, fibrous replacement of atrial musculature by
      mature collagenous tissue produced by the RF current was observed at the left
      inferior atrioventricular junction. In serial sections that included the coronary
      sinus, two distinct nodal structures containing small, pale myocytes within the
      fibrous tissue matrix were identified around the region of the ablation lesion.
      Our case appears to be a unique representation of tissue that was associated with
      the occurrence and maintenance of AT.

PMID- 17005591
TI  - Transcatheter ablation through the cardiac veins in a patient with a
      biventricular device and left ventricular epicardial arrhythmias.
AB  - Left ventricular outflow tract (LVOT) may be a source of repeated premature
      ventricular complexes (PVCs). In symptomatic patients, radiofrequency catheter
      ablation (RFCA) can be effective, either from endocardial or from epicardial
      sites. A 50-year-old patient, with dilated cardiomyopathy (DCM) and severe left
      ventricular (LV) dysfunction, left bundle branch block (LBBB), New York Heart
      Association (NYHA) class IV, received a biventricular implantable
      cardioverter/defibrillator (ICD) in 2002. Despite drug therapy, PVCs were
      frequent (21.019/24 h) including prolonged runs, prompting ICD intervention.
      Premature ventricular complexes showed an inferior axis morphology, with an R/S
      ratio in V3>1, suggesting an LVOT origin. Despite the cardiac resynchronization
      therapy (CRT) device, successful RFCA was performed through the anterior venous
      branch, with a favourable clinical outcome. To our knowledge, this is the first
      case describing epicardial RFCA of a PVC focus from cardiac veins in the presence
      of a CRT device.

PMID- 17005592
TI  - Real-time assessment of acute myocardial ischaemia by an intra-thoracic 6-lead
      ECG: evaluation of a new diagnostic option in the implantable defibrillator.
AB  - AIM: In the presence of coronary artery disease, implantable cardioverter
      defibrillators (ICD) are used effectively for treating life-threatening
      tachyarrhythmias. Continuous monitoring of myocardial ischaemia would provide a
      new diagnostic option in future ICD generations. METHODS AND RESULTS: In 22
      selected patients undergoing coronary angioplasty, percutaneous transluminal
      coronary angioplasty (PTCA), three electrodes, similar to those used in the ICD,
      were inserted aiming to create six intra-thoracic ECG (IT-ECG) leads according to
      Einthoven and Goldberger. In total, 27 PTCA were conducted. The diagnostic
      efficacy for ischaemia assessment was compared with the surface ECG. The IT-ECG
      proved to be more sensitive than conventional ECG in early and overall ischaemia
      assessment. At 30 s of coronary artery occlusion, ischaemic ST-segment
      alterations (> or =0.25 mV) were present in the IT-ECG 2.3 times more often (23
      vs. 10/27 PTCA attempts, P<0.01) and at 90 s 1.4 times more often compared with
      conventional ECG leads (18 vs. 26/27, P<0.05). Intra-thoracic Einthoven 2
      (SVC+RVA vs. ICD-housing) and Goldberger 3 (SVC+ICD-housing vs. RVA) had the
      highest sensitivity (88/85%). Using > or =4 IT-ECG, ischaemia monitoring was
      independent of severity and site of origin. IT-ECG signals showed double ST-T
      signal amplitude (4.19+/-0.6 vs. 2.15+/-0.3 mV, ratio: 1.95, P<0.01) at a QRS/ST
      amplitude ratio similar in the two ECG techniques. CONCLUSION: This study
      provides strong evidence that the ICD-based IT 6-lead ECG would provide a new and
      efficient means of assessing a patient's daily ischaemic burden.

PMID- 17005593
TI  - Health promotion impact factor: join up, no translation.

PMID- 17005594
TI  - Lipid phosphate phosphatases 1 and 3 are localized in distinct lipid rafts.
AB  - Lipid phosphate phosphatases (LPPs), integral membrane proteins with six
      transmembrane domains, dephosphorylate a variety of extracellular lipid
      phosphates. Although LPP3 is already known to bind to Triton X-100-insoluble
      rafts, we here report that LPP1 is also associated with lipid rafts distinct from
      those harboring LPP3. We found that LPP1 was Triton X-100-soluble, but CHAPS
      insoluble in LNCaP cells endogenously expressing LPP1 and several LPP1 cDNA
      transfected cells including NIH3T3 fibroblasts. In addition to the non-ionic
      detergent insolubility, LPP1 further possessed several properties formulated for
      raft-localizing proteins as follows: first, the CHAPS-insolubility was resistant
      to the actin-disrupting drug cytochalasin D; second, the CHAPS-insoluble LPP1
      floated in an Optiprep density gradient; third, the CHAPS insolubility of LPP1
      was lost by cholesterol depletion; and finally, the subcellular distribution
      pattern of LPP1 exclusively overlapped with that of a raft marker, cholera toxin
      B subunit. Interestingly, confocal microscopic analysis showed that LPP1 was
      distributed to membrane compartments distinct from those of LPP3. Analysis using
      various LPP1/LPP3 chimeras revealed that their first extracellular regions
      determine the different Triton X-100 solubilities. These results indicate that
      LPP1 and LPP3 are distributed in distinct lipid rafts that may provide unique
      microenvironments defining their non-redundant physiological functions.

PMID- 17005595
TI  - Age-dependent changes in the expression of superoxide dismutases and catalase are
      associated with ultrastructural modifications in human granulosa cells.
AB  - Limited knowledge exists about changes in follicle quality associated with age.
      The aim of this work was to investigate whether ageing may cause oxidative stress
      mediated alterations in human granulosa cells (GCs) from periovulatory follicles.
      GCs employed in this study were obtained from follicular aspirates of 20 younger
      women (range 27-32 years) and 20 older women (range 38-41 years) undergoing an
      IVF treatment. Results obtained from comparative RT-PCR analysis revealed that
      the mean relative levels of mRNAs coding for superoxide dismutases, Cu, ZnSOD
      (SOD1), MnSOD (SOD2) and catalase were significantly decreased in women > or =38
      years (P < 0.05, Student's t-test). These changes were associated with a reduced
      expression of SOD1, SOD2 and catalase at the protein level. When examined at an
      ultrastructural level, most of the GCs from this group showed defective
      mitochondria and fewer lipid droplets than those observed in the younger group.
      These results indicate that GCs from older patients suffer from age-dependent
      oxidative stress injury and are taken as an evidence for reduced defence against
      reactive oxygen species (ROS) in GCs during reproductive ageing.

PMID- 17005596
TI  - American Cancer Society Guidelines on Nutrition and Physical Activity for cancer
      prevention: reducing the risk of cancer with healthy food choices and physical
      activity.
AB  - The American Cancer Society (ACS) publishes Nutrition and Physical Activity
      Guidelines to serve as a foundation for its communication, policy, and community
      strategies and ultimately, to affect dietary and physical activity patterns among
      Americans. These Guidelines, published every 5 years, are developed by a national
      panel of experts in cancer research, prevention, epidemiology, public health, and
      policy, and as such, they represent the most current scientific evidence related
      to dietary and activity patterns and cancer risk. The ACS Guidelines include
      recommendations for individual choices regarding diet and physical activity
      patterns, but those choices occur within a community context that either
      facilitates or interferes with healthy behaviors. Community efforts are essential
      to create a social environment that promotes healthy food choices and physical
      activity. Therefore, this committee presents one key recommendation for community
      action to accompany the four recommendations for individual choices to reduce
      cancer risk. This recommendation for community action recognizes that a
      supportive social environment is indispensable if individuals at all levels of
      society are to have genuine opportunities to choose healthy behaviors. The ACS
      Guidelines are consistent with guidelines from the American Heart Association and
      the American Diabetes Association for the prevention of coronary heart disease
      and diabetes, as well as for general health promotion, as defined by the
      Department of Health and Human Services' 2005 Dietary Guidelines for Americans.

PMID- 17005597
TI  - Staging soft tissue sarcoma: evolution and change.
AB  - Soft tissue sarcoma (STS) is an extremely heterogeneous group of rare tumors that
      share a putative mesenchymal cell origin. STS can occur in any soft tissue in the
      body, yet all share a common feature of primarily disseminating hematogenously,
      particularly to the lungs. Staging for STS is particularly useful in prognosis,
      design of effective multimodality treatment programs, and comparing treatment
      outcomes from different centers and different eras. The current iteration of AJCC
      STS staging includes Tumor, Grade, Node, and Metastasis with "a" indicating
      superficial and "b" indicating deep designations. Further opportunities to
      improve this process exist, particularly as molecular considerations become more
      apparent, and future evolution into an even more useful STS staging system can be
      anticipated.

PMID- 17005598
TI  - Lymphatic mapping and sentinel node analysis: current concepts and applications.
AB  - Since the introduction of sentinel node biopsy in 1990 as a minimally invasive
      surgical technique for the diagnosis of melanoma lymphatic metastases, the number
      of applications has expanded. We review applications and the current status of
      sentinel node biopsy in melanoma, breast, colon, gastric, esophageal, head and
      neck, thyroid, and lung cancer. Variations on techniques specific to each organ
      are explained, and the current role of sentinel node biopsy in diagnosis and
      treatment is discussed.

PMID- 17005599
TI  - Choices for good health: American Cancer Society Guidelines for Nutrition and
      Physical Activity for cancer prevention.

PMID- 17005600
TI  - Interactions between Na+ channels and Na+-HCO3- cotransporters in the freshwater
      fish gill MR cell: a model for transepithelial Na+ uptake.
AB  - Isolated mitochondria-rich (MR) cells from the rainbow trout gill epithelium were
      subjected to intracellular pH (pH(i)) imaging with the pH-sensitive dye BCECF-AM.
      MR cells were categorized into two distinct functional subtypes based on their
      ability to recover pH(i) from an NH(4)Cl-induced acidification in the absence of
      Na(+). An apparent link between resting pH(i) and Na(+)-independent pH(i)
      recovery was made. We observed a unique pH(i) acidification event that was
      induced by extracellular Na(+) addition. This further classified the mixed MR
      cell population into two functional subtypes: the majority of cells (77%)
      demonstrated the Na(+)-induced pH(i) acidification, whereas the minority (23%)
      demonstrated an alkalinization of pH(i) under the same circumstances. The focus
      of this study was placed on the Na(+)-induced acidification and pharmacological
      analysis via the use of amiloride and phenamil, which revealed that Na(+) uptake
      was responsible for the intracellular acidification. Further experiments revealed
      that pH(i) acidification could be abolished when Na(+) was allowed entry into the
      cell, but the activity of an electrogenic Na(+)-HCO(3)(-) cotransporter (NBC) was
      inhibited by DIDS. The electrogenic NBC activity was supported by a DIDS
      sensitive, Na(+)-induced membrane potential depolarization as observed via
      imaging of the voltage-sensitive dye bis-oxonol. We also demonstrated NBC
      immunoreactivity via Western blotting and immunohistochemistry in gill tissue. We
      propose a model for transepithelial Na(+) uptake occurring via an apical Na(+)
      channel linked to a basolateral, electrogenic NBC in one subpopulation of MR
      cells.

PMID- 17005601
TI  - Computational model of vectorial potassium transport by cochlear marginal cells
      and vestibular dark cells.
AB  - Cochlear marginal cells and vestibular dark cells transport potassium into the
      inner ear endolymph, a potassium-rich fluid, the homeostasis of which is
      essential for hearing and balance. We have formulated an integrated mathematical
      model of ion transport across these epithelia that incorporates the biophysical
      properties of the major ion transporters and channels located in the apical and
      basolateral membranes of the constituent cells. The model is constructed for both
      open- and short-circuit situations to test the extremes of functional capacity of
      the epithelium and predicts the steady-state voltages, ion concentrations, and
      transepithelial currents as a function of various transporter and channel
      densities. We validate the model by establishing that the cells are capable of
      vectorial ion transport consistent with several experimental measurements. The
      model indicates that cochlear marginal cells do not make a significant direct
      contribution to the endocochlear potential and illustrates how changes to the
      activity of specific transport proteins lead to reduced K(+) flux across the
      marginal and dark cell layers. In particular, we investigate the mechanisms of
      loop diuretic ototoxicity and diseases with hearing loss in which K(+) and Cl(-)
      transport are compromised, such as Jervell and Lange-Nielsen syndrome and Bartter
      syndrome, type IV, respectively. Such simulations demonstrate the utility of
      compartmental modeling in investigating the role of ion homeostasis in inner ear
      physiology and pathology.

PMID- 17005602
TI  - Freedom of expression. Focus on "Endoplasmic reticulum stress and the unfolded
      protein response regulate cystic fibrosis transmembrane conductance regulator
      expression".

PMID- 17005603
TI  - Osteopontin localizes to the nucleus of 293 cells and associates with polo-like
      kinase-1.
AB  - Osteopontin (OPN) is a secreted phosphoprotein involved in cellular proliferation
      and associated with tumor progression. Although an intracellular form of OPN has
      been described, its function remains unknown. In this study, a novel nuclear
      location for intracellular OPN and a correlation with cell division were
      demonstrated. OPN distinctly localized to the nucleus in a subset of transiently
      transfected human embryonic kidney 293 cells. Immunoblotting confirmed the
      nuclear location of native OPN, and results from immunofluorescence studies
      suggested an association between nuclear OPN and cell cycle progression. Flow
      cytometry revealed that nuclear and cellular OPN content rose significantly
      during the S and G(2)/M phases, respectively. Treatment of cells with the DNA
      polymerase inhibitor aphidicolin prevented cell cycling and greatly reduced
      cellular OPN content. The intracellular location of OPN coincided with polo-like
      kinase-1 (Plk-1), a member of the polo-like kinase family, which, in part through
      their regulation of centrosome-related events, are integral to successful
      cellular mitosis. OPN and Plk-1 were coimmunoprecipitated from nuclear, but not
      cystoslic, extracts, demonstrating an interaction that is limited to the nucleus,
      presumably during mitosis. Deletion of the COOH terminus of OPN militated against
      nuclear localization and Plk-1 interaction. Elevated expression of OPN was also
      associated with an increase in the number of multinucleate 293 cells, whereas
      transfection of the COOH-terminal-deleted OPN decreased the percentage of
      multinucleate cells below basal levels. These findings implicate intranuclear OPN
      as a participant in the process of cell duplication.

PMID- 17005605
TI  - Transmembrane domain histidines contribute to regulation of AE2-mediated anion
      exchange by pH.
AB  - Activity of the AE2/SLC4A2 anion exchanger is modulated acutely by pH,
      influencing the transporter's role in regulation of intracellular pH (pH(i)) and
      epithelial solute transport. In Xenopus oocytes, heterologous AE2-mediated Cl(
      )/Cl(-) and Cl(-)/HCO(3)(-) exchange are inhibited by acid pH(i) or extracellular
      pH (pH(o)). We have investigated the importance to pH sensitivity of the eight
      histidine (His) residues within the AE2 COOH-terminal transmembrane domain (TMD).
      Wild-type mouse AE2-mediated Cl(-)/Cl(-) exchange, measured as DIDS-sensitive
      (36)Cl(-) efflux from Xenopus oocytes, was experimentally altered by varying
      pH(i) at constant pH(o) or varying pH(o). Pretreatment of oocytes with the His
      modifier diethylpyrocarbonate (DEPC) reduced basal (36)Cl(-) efflux at pH(o) 7.4
      and acid shifted the pH(o) vs. activity profile of wild-type AE2, suggesting that
      His residues might be involved in pH sensing. Single His mutants of AE2 were
      generated and expressed in oocytes. Although mutation of H1029 to Ala severely
      reduced transport and surface expression, other individual His mutants exhibited
      wild-type or near-wild-type levels of Cl(-) transport activity with retention of
      pH(o) sensitivity. In contrast to the effects of DEPC on wild-type AE2, pH(o)
      sensitivity was significantly alkaline shifted for mutants H1144Y and H1145A and
      the triple mutants H846/H849/H1145A and H846/H849/H1160A. Although all functional
      mutants retained sensitivity to pH(i), pH(i) sensitivity was enhanced for AE2
      H1145A. The simultaneous mutation of five or more His residues, however, greatly
      decreased basal AE2 activity, consistent with the inhibitory effects of DEPC
      modification. The results show that multiple TMD His residues contribute to basal
      AE2 activity and its sensitivity to pH(i) and pH(o).

PMID- 17005604
TI  - Advanced glycation end products induce apoptosis in fibroblasts through
      activation of ROS, MAP kinases, and the FOXO1 transcription factor.
AB  - Advanced glycation end products (AGEs) are elevated in aged and diabetic
      individuals and are associated with pathological changes associated with both.
      Previously we demonstrated that the AGE N(epsilon)-(carboxymethyl)lysine (CML)
      collagen induced fibroblast apoptosis through the cytoplasmic and mitochondrial
      pathways and the global induction of proapoptotic genes. In the present study we
      investigated upstream mechanisms of CML-collagen-induced apoptosis. CML-collagen
      induced activation of the proapoptotic transcription factor FOXO1 compared with
      unmodified collagen. When FOXO1 was silenced, CML-collagen-stimulated apoptosis
      was reduced by approximately 75% compared with fibroblasts incubated with
      nonsilencing small interfering RNA, demonstrating the functional significance of
      FOXO1 activation (P < 0.05). CML-collagen but not control collagen also induced a
      3.3-fold increase in p38 and a 5.6-fold increase in JNK(1/2) activity (P < 0.05).
      With the use of specific inhibitors, activation of p38 and JNK was shown to play
      an important role in CML-collagen-induced activation of FOXO1 and caspase-3.
      Moreover, inhibition of p38 and JNK reduced CML-collagen-stimulated apoptosis by
      48 and 57%, respectively, and by 89% when used together (P < 0.05). In contrast,
      inhibition of the phosphatidylinositol 3-kinase/Akt pathway enhanced FOXO1
      activation. p38 and JNK stimulation by CML-collagen was almost entirely blocked
      when formation of ROS was inhibited and was partially reduced by NO and ceramide
      inhibitors. These inhibitors also reduced apoptosis to a similar extent. Together
      these data support a model in which AGE-induced apoptosis involves the formation
      of ROS, NO, and ceramide and leads to p38 and JNK MAP kinase activation, which in
      turn induces FOXO1 and caspase-3.

PMID- 17005606
TI  - M(1) and M(2) muscarinic acetylcholine receptor subtypes mediate Ca(2+) channel
      current inhibition in rat sympathetic stellate ganglion neurons.
AB  - Muscarinic acetylcholine receptors (mAChRs) are known to mediate the
      acetylcholine inhibition of Ca(2+) channels in central and peripheral neurons.
      Stellate ganglion (SG) neurons provide the main sympathetic input to the heart
      and contribute to the regulation of heart rate and myocardial contractility.
      Little information is available regarding mAChR regulation of Ca(2+) channels in
      SG neurons. The purpose of this study was to identify the mAChR subtypes that
      modulate Ca(2+) channel currents in rat SG neurons innervating heart muscle.
      Accordingly, the modulation of Ca(2+) channel currents by the muscarinic
      cholinergic agonist, oxotremorine-methiodide (Oxo-M), and mAChR blockers was
      examined. Oxo-M-mediated mAChR stimulation led to inhibition of Ca(2+) currents
      through voltage-dependent (VD) and voltage-independent (VI) pathways. Pre
      exposure of SG neurons to the M(1) receptor blocker, M(1)-toxin, resulted in VD
      inhibition of Ca(2+) currents after Oxo-M application. On the other hand, VI
      modulation of Ca(2+) currents was observed after pretreatment of cells with
      methoctramine (M(2) mAChR blocker). The Oxo-M-mediated inhibition was nearly
      eliminated in the presence of both M(1) and M(2) mAChR blockers but was unaltered
      when SG neurons were exposed to the M(4) mAChR toxin, M(4)-toxin. Finally, the
      results from single-cell RT-PCR and immunofluorescence assays indicated that M(1)
      and M(2) receptors are expressed and located on the surface of SG neurons.
      Overall, the results indicate that SG neurons that innervate cardiac muscle
      express M(1) and M(2) mAChR, and activation of these receptors leads to
      inhibition of Ca(2+) channel currents through VI and VD pathways, respectively.

PMID- 17005607
TI  - Stimulus selectivity is enhanced by voltage-dependent conductances in combination
      sensitive neurons.
AB  - Central sensory neurons often respond selectively to particular combinations of
      stimulus attributes, but we know little about the underlying cellular mechanisms.
      The weakly electric fish Gymnarchus discriminates the sign of the frequency
      difference (Df) between a neighbor's electric organ discharge (EOD) and its own
      EOD by comparing temporal patterns of amplitude modulation (AM) and phase
      modulation (PM). Sign-selective neurons in the midbrain respond preferentially to
      either positive frequency differences (Df >0 selective) or negative frequency
      differences (Df <0 selective). To study the mechanisms of combination
      sensitivity, we made whole cell intracellular recordings from sign-selective
      midbrain neurons in vivo and recorded postsynaptic potential (PSP) responses to
      AM, PM, Df >0, and Df <0. Responses to AM and PM consisted of alternating
      excitatory and inhibitory PSPs. These alternating responses were in phase for the
      preferred sign of Df and offset for the nonpreferred sign of Df. Therefore a
      certain degree of sign selectivity was predicted by a linear sum of the responses
      to AM and PM. Responses to the nonpreferred sign of Df, but not the preferred
      sign of Df, were substantially weaker than linear predictions, causing a
      significant increase in the actual degree of sign selectivity. By using various
      levels of current clamp and comparing our results to simple models of synaptic
      integration, we demonstrate that this decreased response to the nonpreferred sign
      of Df is caused by a reduction in voltage-dependent excitatory conductances. This
      finding reveals that nonlinear decoders, in the form of voltage-dependent
      conductances, can enhance the selectivity of single neurons for particular
      combinations of stimulus attributes.

PMID- 17005608
TI  - Delay of movement caused by disruption of cortical preparatory activity.
AB  - We tested the hypothesis that delay-period activity in premotor cortex is
      essential to movement preparation. During a delayed-reach task, we used
      subthreshold intracortical microstimulation to disrupt putative "preparatory"
      activity. Microstimulation led to a highly specific increase in reach reaction
      time. Effects were largest when activity was disrupted around the time of the go
      cue. Earlier disruptions, which presumably allowed movement preparation time to
      recover, had only a weak impact. Furthermore, saccadic reaction time showed
      little or no increase. Finally, microstimulation of nearby primary motor cortex,
      even when slightly suprathreshold, had little effect on reach reaction time.
      These findings provide the first evidence, of a causal and temporally specific
      nature, that activity in premotor cortex is fundamental to movement preparation.
      Furthermore, although reaction times were increased, the movements themselves
      were essentially unperturbed. This supports the suggestion that movement
      preparation is an active and actively monitored process and that movement can be
      delayed until inaccuracies are repaired. These results are readily interpreted in
      the context of the recently developed optimal-subspace hypothesis.

PMID- 17005609
TI  - Temporal dynamics of figure-ground segregation in human vision.
AB  - The segregation of figure from ground is arguably one of the most fundamental
      operations in human vision. Neural signals reflecting this operation appear in
      cortex as early as 50 ms and as late as 300 ms after presentation of a visual
      stimulus, but it is not known when these signals are used by the brain to
      construct the percepts of figure and ground. We used psychophysical reverse
      correlation to identify the temporal window for figure-ground signals in human
      perception and found it to lie within the range of 100-160 ms. Figure enhancement
      within this narrow temporal window was transient rather than sustained as may be
      expected from measurements in single neurons. These psychophysical results prompt
      and guide further electrophysiological studies.

PMID- 17005610
TI  - Context-dependent modulation of interlimb cutaneous reflexes in arm muscles as a
      function of stability threat during walking.
AB  - Cutaneous reflexes evoked in the muscles of the arms with electrical stimulation
      of nerves of the foot ("interlimb reflexes") are observed during walking. These
      reflexes have been suggested to coordinate the actions of the legs and arms when
      walking is disturbed. Recently, we showed that cutaneous reflexes evoked in the
      leg muscles after stimulation at the foot are modulated according to the level of
      postural threat during walking. We hypothesized that the amplitude of interlimb
      cutaneous reflexes would similarly be modulated when subjects walk in unstable
      environments. Subjects walked on a treadmill under four walking conditions: 1)
      normal; 2) normal with unpredictable anterior-posterior (AP) perturbations; 3)
      arms crossed; and 4) arms crossed with unpredictable AP perturbations. Interlimb
      reflexes evoked from electrical stimulation of the right superficial peroneal or
      sural nerves were recorded bilaterally, at four points of the step cycle. These
      reflexes were compared between conditions in which the arms were moving in a
      similar manner: 1) normal versus AP walking and 2) arms crossed versus arms
      crossed with AP perturbations. Differences in reflex amplitudes between arms
      crossed conditions were observed in most upper limb muscles when subjects were
      perturbed while walking compared with undisturbed walking. This effect was less
      apparent when the arms were swinging freely. The results indicate that the
      strength of interlimb connections is influenced by the level of postural threat
      (i.e., the context of the behavior), thereby suggesting that these reflexes serve
      a functional link between the legs and arms during locomotion.

PMID- 17005611
TI  - Beta oscillatory activity in the subthalamic nucleus and its relation to
      dopaminergic response in Parkinson's disease.
AB  - Recent studies suggest that beta (15-30 Hz) oscillatory activity in the
      subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD)
      and may interfere with movement execution. Dopaminergic medications decrease beta
      activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by
      disrupting this oscillatory activity. Depth recordings from PD patients have
      demonstrated beta oscillatory neuronal and local field potential (LFP) activity
      in STN, although its prevalence and relationship to neuronal activity are
      unclear. In this study, we recorded both LFP and neuronal spike activity from the
      STN in 14 PD patients during functional neurosurgery. Of 200 single- and
      multiunit recordings 56 showed significant oscillatory activity at about 26 Hz
      and 89% of these were coherent with the simultaneously recorded LFP. The
      incidence of neuronal beta oscillatory activity was significantly higher in the
      dorsal STN (P = 0.01) and corresponds to the significantly increased LFP beta
      power recorded in the same region. Of particular interest was a significant
      positive correlation between the incidence of oscillatory neurons and the
      patient's benefit from dopaminergic medications, but not with baseline motor
      deficits off medication. These findings suggest that the degree of neuronal beta
      oscillatory activity is related to the magnitude of the response of the basal
      ganglia to dopaminergic agents rather than directly to the motor symptoms of PD.
      The study also suggests that LFP beta oscillatory activity is generated largely
      within the dorsal portion of the STN and can produce synchronous oscillatory
      activity of the local neuronal population.

PMID- 17005612
TI  - Accurate real-time feedback of surface EMG during fMRI.
AB  - Real-time acquisition of EMG during functional MRI (fMRI) provides a novel method
      of controlling motor experiments in the scanner using feedback of EMG. Because of
      the redundancy in the human muscle system, this is not possible from recordings
      of joint torque and kinematics alone, because these provide no information about
      individual muscle activation. This is particularly critical during brain imaging
      because brain activations are not only related to joint torques and kinematics
      but are also related to individual muscle activation. However, EMG collected
      during imaging is corrupted by large artifacts induced by the varying magnetic
      fields and radio frequency (RF) pulses in the scanner. Methods proposed in
      literature for artifact removal are complex, computationally expensive, and
      difficult to implement for real-time noise removal. We describe an acquisition
      system and algorithm that enables real-time acquisition for the first time. The
      algorithm removes particular frequencies from the EMG spectrum in which the noise
      is concentrated. Although this decreases the power content of the EMG, this
      method provides excellent estimates of EMG with good resolution. Comparisons show
      that the cleaned EMG obtained with the algorithm is, like actual EMG, very well
      correlated with joint torque and can thus be used for real-time visual feedback
      during functional studies.

PMID- 17005613
TI  - Kappa opioid receptor (KOR) and GAD67 immunoreactivity are found in OFF and
      NEUTRAL cells in the rostral ventromedial medulla.
AB  - This study combines functional and anatomical characterization of neurons in the
      rostral ventromedial medulla (RVM) to show distinct neurochemical phenotypes
      between functional classes of neurons. The RVM contains three functional classes
      of neurons: off cells show a pause in spontaneous activity prior to a nociceptive
      withdrawal reflex; on cell activity increases prior to a nociceptive reflex; and
      neutral cell activity does not change significantly during the nociceptive
      reflex. We determined if serotonin, glutamate decarboxylase (GAD67), or the kappa
      opioid receptor (KOR) were differentially located within these cell types as
      predicted by previous studies. In this study, RVM neurons were recorded
      extracellularly, functionally characterized, and juxtacellularly labeled with
      biotinamide. Fixed sections were processed for detection of biotinamide and
      immunfluorescence either for serotonin or for KOR and GAD67. In the first study,
      serotonin was found exclusively in a subset of neutral cells (33%). These data
      substantiate previous findings that serotonin is found in some neutral cells
      whose role in nociception remains unclear. In the second study, we found KOR
      immunoreactivity in most off (86%) and neutral (80%) cells but rarely in on (13%)
      cells. We also found GAD67 immunoreactivity in most off (93%) and neutral cells
      (80%) but less frequently in on cells (63%). Most KOR-immunoreactive cells (16 of
      17) also contained GAD67 immunoreactivity regardless of cell classification.
      These findings support the hypothesis that KOR agonists directly inhibit off and
      neutral cell activity. The majority of the off and neutral cells are GABAergic,
      and some on cells are also GABAergic.

PMID- 17005614
TI  - Hemispheric mapping of secondary somatosensory cortex in the rat.
AB  - This study used high-resolution hemispheric mapping of somatosensory evoked
      potentials to determine the number and organization of secondary somatosensory
      areas (SII) in rat cortex. Two areas, referred to as SII and PV (parietoventral),
      revealed complete (SII) or nearly complete (PV) body maps. The vibrissa and
      somatic representation of SII was upright, rostrally oriented, and immediately
      lateral to primary somatosensory cortex (SI), with a dominant face
      representation. Vibrissa representations in SII were highly organized, with the
      rows staggered rostrally along the mediolateral axis. Area PV was approximately
      one fifth the size of SII, and located rostral and lateral to auditory cortex. PV
      had a rostrally oriented and inverted body representation that was dominated by
      the distal extremities, with little representation of the face or vibrissae.
      These data support the conclusion that in the rat, as in other species, SII and
      PV represent anatomically and functionally distinct areas of secondary
      somatosensory cortex.

PMID- 17005615
TI  - Excitatory muscarinic modulation strengthens virtual nicotinic synapses on
      sympathetic neurons and thereby enhances synaptic gain.
AB  - Acetylcholine excites many neuronal types by binding to postsynaptic m1
      muscarinic receptors that signal to ion channels through the G(q/11) protein. To
      investigate the functional significance of this metabotropic pathway in
      sympathetic ganglia, we studied how muscarinic excitation modulated the
      integration of virtual nicotinic excitatory postsynaptic potentials (EPSPs)
      created in dissociated bullfrog B-type sympathetic neurons with the dynamic-clamp
      technique. Muscarine (1 muM) strengthened the impact of virtual synapses by
      reducing the artificial nicotinic conductance required to reach the postsynaptic
      firing threshold from 20.9 +/- 5.4 to 13.1 +/- 3.1 nS. Consequently,
      postganglionic action potential output increased by 4-215% when driven by
      different patterns of virtual presynaptic activity that were chosen to reflect
      the range of physiological firing rates and convergence levels seen in amphibian
      and mammalian sympathetic ganglia. In addition to inhibiting the M-type K(+)
      conductance, muscarine activated a leak conductance in three of 37 cells. When
      this leak conductance was reproduced with the dynamic clamp, it also acted to
      strengthen virtual nicotinic synapses and enhance postganglionic spike output.
      Combining pharmacological M-conductance suppression with virtual leak activation,
      at resting potentials between -50 and -55 mV, produced synergistic strengthening
      of nicotinic synapses and an increase in the integrated postganglionic spike
      output. Together, these results reveal how muscarinic activation of a branched
      metabotropic pathway can enhance integration of fast EPSPs by modulating their
      effective strength. The results also support the hypothesis that muscarinic
      synapses permit faster and more accurate feedback control of autonomic behaviors
      by generating gain through synaptic amplification in sympathetic ganglia.

PMID- 17005616
TI  - Dopamine has bidirectional effects on synaptic responses to cortical inputs in
      layer II of the lateral entorhinal cortex.
AB  - Dopaminergic modulation of neuronal function has been extensively studied in the
      prefrontal cortex, but much less is known about its effects on glutamate-mediated
      synaptic transmission in the entorhinal cortex. The mesocortical dopamine system
      innervates the superficial layers of the lateral entorhinal cortex and may
      therefore modulate sensory inputs to this area. In awake rats, systemic
      administration of the dopamine reuptake inhibitor GBR12909 (10 mg/kg, ip)
      enhanced extracellular dopamine levels in the entorhinal cortex and significantly
      facilitated field excitatory postsynaptic potentials (fEPSPs) in layer II evoked
      by piriform cortex stimulation. An analysis of the receptor subtypes involved in
      the facilitation of evoked fEPSPs was conducted using horizontal slices of
      lateral entorhinal cortex in vitro. The effects of 15-min bath application of
      dopamine on synaptic responses were bidirectional and concentration dependent.
      Synaptic responses were enhanced by 10 microM dopamine and suppressed by
      concentrations of 50 and 100 microM. The D(1)-receptor antagonist SCH23390 (50
      microM) blocked the significant facilitation of synaptic responses induced by 10
      microM dopamine and the D(2)-receptor antagonist sulpiride (50 microM) prevented
      the suppression of fEPSPs observed with higher concentrations of dopamine. We
      propose here that dopamine release in the lateral entorhinal cortex, acting
      through D(1) receptors, can lead to an enhancement of the salience of sensory
      representations carried to this region from adjacent sensory cortices.

PMID- 17005617
TI  - Assessment of stimulus-induced changes in human V1 visual field maps.
AB  - Visual cortex contains a set of field maps in which nearby scene points are
      represented in the responses of nearby neurons. We tested a recent hypothesis
      that the visual field map in primary visual cortex (V1) is dynamic, changing in
      response to stimulus motion direction. The original experimental report
      replicates, but further experimental and analytical investigations do not
      support, the interpretation of the results. The V1 map remains invariant when
      measured using stimuli moving in different directions. The measurements can be
      explained by small and systematic response amplitude differences that arise when
      probing with stimuli moving in different directions.

PMID- 17005618
TI  - Sleep-related spike bursts in HVC are driven by the nucleus interface of the
      nidopallium.
AB  - The function and the origin of replay of motor activity during sleep are
      currently unknown. Spontaneous activity patterns in the nucleus robustus of the
      arcopallium (RA) and in HVC (high vocal center) of the sleeping songbird resemble
      premotor patterns in these areas observed during singing. We test the hypothesis
      that the nucleus interface of the nidopallium (NIf) has an important role for
      initiating and shaping these sleep-related activity patterns. In head-fixed,
      sleeping zebra finches we find that injections of the GABA(A)-agonist muscimol
      into NIf lead to transient abolishment of premotor-like bursting activity in HVC
      neurons. Using antidromic activation of NIf neurons by electrical stimulation in
      HVC, we are able to distinguish a class of HVC-projecting NIf neurons from a
      second class of NIf neurons. Paired extracellular recordings in NIf and HVC show
      that NIf neurons provide a strong bursting drive to HVC. In contrast to HVC
      neurons, whose bursting activity waxes and wanes in burst epochs, individual NIf
      projection neurons are nearly continuously bursting and tend to burst only once
      on the timescale of song syllables. Two types of HVC projection neurons-premotor
      and striatal projecting-respond differently to the NIf drive, in agreement with
      notions of HVC relaying premotor signals to RA and an anticipatory copy thereof
      to areas of a basal ganglia pathway.

PMID- 17005619
TI  - Hemispheric asymmetry in memory-guided pointing during single-pulse transcranial
      magnetic stimulation of human parietal cortex.
AB  - Dorsal posterior parietal cortex (PPC) has been implicated through single-unit
      recordings, neuroimaging data, and studies of brain-damaged humans in the spatial
      guidance of reaching and pointing movements. The present study examines the
      causal effect of single-pulse transcranial magnetic stimulation (TMS) over the
      left and right dorsal posterior parietal cortex during a memory-guided "reach-to
      touch" movement task in six human subjects. Stimulation of the left parietal
      hemisphere significantly increased endpoint variability, independent of visual
      field, with no horizontal bias. In contrast, right parietal stimulation did not
      increase variability, but instead produced a significantly systematic leftward
      directional shift in pointing (contralateral to stimulation site) in both visual
      fields. Furthermore, the same lateralized pattern persisted with left-hand
      movement, suggesting that these aspects of parietal control of pointing movements
      are spatially fixed. To test whether the right parietal TMS shift occurs in
      visual or motor coordinates, we trained subjects to point correctly to optically
      reversed peripheral targets, viewed through a left-right Dove reversing prism.
      After prism adaptation, the horizontal pointing direction for a given visual
      target reversed, but the direction of shift during right parietal TMS did not
      reverse. Taken together, these data suggest that induction of a focal current
      reveals a hemispheric asymmetry in the early stages of the putative spatial
      processing in PPC. These results also suggest that a brief TMS pulse modifies the
      output of the right PPC in motor coordinates downstream from the adapted
      visuomotor reversal, rather than modifying the upstream visual coordinates of the
      memory representation.

PMID- 17005620
TI  - Motor deficits in homozygous and heterozygous p/q-type calcium channel mutants.
AB  - P/Q-type voltage-dependent Ca(2+) channels (VDCCs) are highly expressed in the
      cerebellum, and mutations of these channels are associated with disrupted motor
      function. Several allelic variants of the alpha1A pore-forming subunit of P/Q
      type VDCCs have been described, and mice homozygous for these mutations exhibit
      gait ataxia, as do alpha1A knockout mice. Here we report that heterozygous
      alpha1A mutants also have a motor phenotype. Mice heterozygous for the leaner and
      alpha1A knockout mutations exhibit impaired motor learning in the vestibulo
      ocular reflex (VOR), suggesting that subtle disruption of P/Q Ca(2+) currents is
      sufficient to disrupt motor function. Basal VOR and optokinetic reflex
      performance were normal in the heterozygotes but severely impaired in the leaner
      and alpha1A knockout homozygotes.

PMID- 17005621
TI  - Computational motor control: redundancy and invariance.
AB  - The nervous system controls the behavior of complex kinematically redundant
      biomechanical systems. How it computes appropriate commands to generate movements
      is unknown. Here we propose a model based on the assumption that the nervous
      system: 1) processes static (e.g., gravitational) and dynamic (e.g., inertial)
      forces separately; 2) calculates appropriate dynamic controls to master the
      dynamic forces and progress toward the goal according to principles of optimal
      feedback control; 3) uses the size of the dynamic commands (effort) as an
      optimality criterion; and 4) can specify movement duration from a given level of
      effort. The model was used to control kinematic chains with 2, 4, and 7 degrees
      of freedom [planar shoulder/elbow, three-dimensional (3D) shoulder/elbow, 3D
      shoulder/elbow/wrist] actuated by pairs of antagonist muscles. The muscles were
      modeled as second-order nonlinear filters and received the dynamics commands as
      inputs. Simulations showed that the model can quantitatively reproduce
      characteristic features of pointing and grasping movements in 3D space, i.e.,
      trajectory, velocity profile, and final posture. Furthermore, it accounted for
      amplitude/duration scaling and kinematic invariance for distance and load. These
      results suggest that motor control could be explained in terms of a limited set
      of computational principles.

PMID- 17005622
TI  - Coexistence of muscarinic long-term depression with electrically induced long
      term potentiation and depression at CA3-CA1 synapses.
AB  - Our laboratory recently characterized a form of long-term depression (LTD) at CA3
      CA1 synapses mediated by M1 muscarinic receptors (mAChRs), termed muscarinic LTD
      (mLTD). mLTD is both activity and NMDAR dependent, characteristics shared by
      forms of synaptic plasticity thought to be relevant to learning and memory,
      including long-term potentiation (LTP) induced by high-frequency stimulation (HFS
      LTP) and long-term depression induced by low-frequency stimulation (LFS-LTD).
      However, it remains unclear whether mLTD can occur sequentially with these
      electrically induced forms of hippocampal plasticity or whether mLTD might
      interact with them. The first goal of this study was to examine the interplay of
      mLTD and HFS-LTP. We report that mLTD expression does not alter subsequent
      induction of HFS-LTP and, further, at synapses expressing HFS-LTP, mLTD can
      mediate a novel form of depotentiation. The second goal was to determine whether
      mLTD would alter LFS-LTD induction and/or expression. Although we show that mLTD
      is occluded by saturation of LFS-LTD, suggesting mechanistic similarity between
      these two plasticities, saturation of mLTD does not occlude LFS-LTD.
      Surprisingly, however, the LFS-LTD that follows cholinergic receptor activation
      is NMDAR independent, indicating that application of muscarinic agonist induces a
      change in the induction mechanism required for LFS-LTD. These data demonstrate
      that mLTD can coexist with electrically induced forms of synaptic plasticity and
      support the hypothesis that mLTD is one of the mechanisms by which the
      cholinergic system modulates hippocampal function.

PMID- 17005623
TI  - Nonuniform distribution of reach-related and torque-related activity in upper arm
      muscles and neurons of primary motor cortex.
AB  - The present study examined the activity of primate shoulder and elbow muscles
      using a novel reaching task. We enforced similar patterns of center-out movement
      while the animals countered viscous loads at their shoulder, elbow, both joints,
      or neither joint. Accordingly, we could examine reach-related activity during the
      unloaded condition and torque-related activity by comparing activity across load
      conditions. During unloaded reaching the upper arm muscles exhibited a bimodal
      distribution of preferred hand direction. Maximal reach-related activity occurred
      with hand movements mostly toward or away from the body. Arm muscles also
      exhibited a bimodal distribution of their preferred torque direction. Maximal
      torque-related activity typically occurred with shoulder-extension/elbow-flexion
      torque or shoulder-flexion/elbow-extension torque. Similar biases in reach
      related and torque-related activity could be reproduced by optimizing a global
      measure of muscle activity. These biases were also observed in the neural
      activity of primary motor cortex (M1). The parallels between M1 and muscular
      activity demonstrate another link between motor cortical processing and the motor
      periphery and may reflect an optimization process performed by the sensorimotor
      system.

PMID- 17005624
TI  - Nutrient intake and risk of non-Hodgkin's lymphoma.
AB  - The mechanisms through which diet may influence the development of non-Hodgkin's
      lymphoma (NHL) are unclear but can be better understood by examining associations
      between nutrient consumption and NHL risk. Between 2000 and 2002, 591 NHL cases
      and 460 population-based controls in Sweden completed a semiquantitative food
      frequency questionnaire. Unconditional logistic regression was performed to
      estimate odds ratios and 95% confidence intervals for associations with nutrient
      intake; all statistical tests were two sided. Dietary intake of most
      macronutrients was not associated with risk of NHL or its common subtypes.
      Consumption of omega-3 or marine fatty acids was associated with decreased risk
      of NHL and chronic lymphocytic lymphoma, and dietary fiber was associated with
      lower risk of all subtypes examined. When the highest and the lowest quartiles of
      marine fat intake were compared, the odds ratio for NHL risk was 0.6 (95%
      confidence interval: 0.4, 0.9), ptrend=0.03; for dietary fiber intake, the
      corresponding odds ratio was 0.5 (95% confidence interval: 0.3, 0.7),
      ptrend<0.001. Dietary consumption of beta-carotene or alpha-tocopherol was
      associated with lower NHL risk, whereas intake of calcium or retinol was
      associated with increased NHL risk. Nutrients that affect inflammation, vitamin D
      activity, oxidative DNA damage, or DNA methylation may be associated with risk of
      NHL.

PMID- 17005625
TI  - Association of selective and conventional nonsteroidal antiinflammatory drugs
      with acute renal failure: A population-based, nested case-control analysis.
AB  - Conventional nonsteroidal antiinflammatory drugs (NSAIDs) are associated with
      acute renal failure, but cyclooxygenase-2 inhibitors have not been comparatively
      evaluated. The authors conducted a nested case-control study to assess the
      association between exposure to NSAIDs, including cyclooxygenase-2 inhibitors,
      and hospitalization for acute renal failure. They identified 121,722 new NSAID
      users older than age 65 years from the administrative health care databases of
      Quebec, Canada, in 1999-2002. Data for 4,228 cases and 84,540 controls matched on
      age and follow-up time were analyzed by using conditional logistic regression,
      adjusted for sex, age, health status, health care utilization measures, exposure
      to contrast agents, and nephrotoxic medications. The risk of acute renal failure
      for all NSAIDs combined was highest within 30 days of treatment initiation
      (adjusted rate ratio (RR) = 2.05, 95% confidence interval (CI): 1.61, 2.60) and
      receded thereafter. The association with acute renal failure within 30 days of
      therapy initiation was comparable for rofecoxib (RR = 2.31, 95% CI: 1.73, 3.08),
      naproxen (RR = 2.42, 95% CI: 1.52, 3.85), and nonselective, non-naproxen NSAIDs
      (RR = 2.30, 95% CI: 1.60, 3.32) but was borderline lower for celecoxib (RR =1.54,
      95% CI: 1.14, 2.09; test for interaction comparing celecoxib with rofecoxib, p =
      0.057). There was a significant association for both selective and nonselective
      NSAIDs with acute renal failure, but confirmatory studies are required.

PMID- 17005626
TI  - The question of nonlinearity in the dose-response relation between particulate
      matter air pollution and mortality: can Akaike's Information Criterion be trusted
      to take the right turn?
AB  - The shape of the dose-response relation between particulate matter air pollution
      and mortality is crucial for public health assessment, and departures of this
      relation from linearity could have important regulatory consequences. A number of
      investigators have studied the shape of the particulate matter-mortality dose
      response relation and concluded that the relation could be adequately described
      by a linear model. Some of these researchers examined the hypothesis of linearity
      by comparing Akaike's Information Criterion (AIC) values obtained under linear,
      piecewise linear, and spline alternative models. However, at the current time,
      the efficacy of the AIC in this context has not been assessed. The authors
      investigated AIC as a means of comparing competing dose-response models, using
      data from Cook County, Illinois, for the period 1987-2000. They found that if
      nonlinearities exist, the AIC is not always successful in detecting them. In a
      number of the scenarios considered, AIC was equivocal, picking the correct
      simulated dose-response model about half of the time. These findings suggest that
      further research into the shape of the dose-response relation using alternative
      model selection criteria may be warranted.

PMID- 17005627
TI  - Activation of maternal Epstein-Barr virus infection and risk of acute leukemia in
      the offspring.
AB  - After identifying an association between maternal Epstein-Barr virus (EBV)
      reactivation and acute lymphoblastic leukemia (ALL), the authors analyzed a
      nested case-control study within Finnish and Icelandic maternity cohorts with 7
      million years of follow-up to confirm EBV's role in ALL. Offspring of 550,000
      mothers were followed up to age 15 years during 1975-1997 by national cancer
      registries to identify leukemia cases. Mothers of cases and three quarters of
      matched mothers of controls were identified by national population registers.
      First-trimester sera from mothers of 304 ALL cases and 39 non-ALL cases and from
      943 mothers of controls were analyzed for antibodies to viral capsid antigen,
      early antigen, and EBV transactivator protein ZEBRA. Relative risk, estimated as
      odds ratio (95% confidence interval), was adjusted for birth order and sibship
      size. Combining early antigen and/or ZEBRA immunoglobulin G antibodies with the
      presence of viral capsid antigen immunoglobulin M antibodies did not increase the
      estimate for ALL risk for viral capsid antigen immunoglobulin M alone (odds ratio
      = 1.9, 95% confidence interval: 1.2, 3.0). Both ZEBRA immunoglobulin G antibodies
      and viral capsid antigen immunoglobulin M antibodies were associated with an
      increased risk of non-ALL in the offspring (odds ratio = 4.5, 95% confidence
      interval: 1.3, 16; odds ratio = 5.6, 95% confidence interval: 1.1, 29,
      respectively), suggesting EBV reactivation in the mothers of non-ALL cases. EBV
      reactivation may be associated with a proportion of childhood leukemia.

PMID- 17005628
TI  - Analyses of TCR clustering at the T cell-antigen-presenting cell interface and
      its impact on the activation of naive CD4+ T cells.
AB  - The role of micrometer-scale clustering of TCRs at the T cell-antigen-presenting
      cell (APC) interface in T cell activation is an area of active investigation.
      Here we have investigated the impact of variations in the extent of TCR
      clustering on the activation of naive CD4+ T cells. These T cells are derived
      from transgenic (tg) mice expressing TCRs (172.10 and 1934.4) specific for the N
      terminal nonapeptide of MBP bound to I-A(u), and are associated with murine
      experimental autoimmune encephalomyelitis (EAE). The 172.10 TCR has a
      approximately 4-fold higher affinity for antigen relative to the 1934.4 TCR,
      allowing us to compare the properties of two tg T cells of different avidities.
      We observe that variations in large-scale TCR clustering at the T cell-APC
      interface do not correlate well with the extent of activation (CD25 or CD69 up
      regulation and IL-2 or IFN-gamma production). Efficient activation can also be
      achieved in the absence of micrometer-scale TCR clustering, indicating that this
      is not a prerequisite for the effective stimulation of naive T cells.

PMID- 17005629
TI  - Sonic hedgehog promotes CD4+ T lymphocyte proliferation and modulates the
      expression of a subset of CD28-targeted genes.
AB  - Sonic hedgehog (Shh) is a crucial morphogen in the development of numerous
      tissues and organs, including the nervous system, gastrointestinal tract and
      lung. Recent findings suggest that Shh plays an important role in thymocyte
      development and peripheral T cell function. Here we report that the Shh
      receptors, patched and smoothened, are expressed in resting and activated T cells
      and their expression is regulated upon T cell activation. Shh protein is also
      detected on the surface of freshly isolated T cells. Although exogenous Shh alone
      does not activate resting T cells, it exhibits co-stimulatory activity which is
      reflected in its ability to potentiate CD3-mediated proliferation and cytokine
      production by CD4(+) T cells. The co-stimulatory effect is most prominent at sub
      optimal TCR stimulation level. Gene expression analysis reveals that Shh
      signaling in CD4(+) T cells modulates a different set of transcriptional targets
      from that in neuronal cells. Furthermore, Shh co-stimulation modulates the
      expression of a subset of CD28-responsive genes, including cyclin A and B cell
      translocation gene 2.

PMID- 17005630
TI  - The enigma of young age.

PMID- 17005631
TI  - The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer.
      A phase I trial of the AGO-OVAR.
AB  - BACKGROUND: Abagovomab is a murine anti-idiotypic antibody against the antigen CA
      125 which has been shown to elicit humoral and cellular immune responses against
      ovarian cancer (oc). PATIENTS AND METHODS: This phase I trial included 36
      patients with recurrent oc comparing two subcutaneous (s.c.) vaccination
      schedules: nine (group L) versus six injections (group S), 18 patients in each
      group. Four injections of 2.0 mg abagovomab were administered every 2 weeks and
      then two or five additional doses monthly. Primary endpoint was drop-out rate due
      to toxicity, and the secondary endpoint was analysis of immunological response.
      RESULTS: Treatment was completed in eight (44%) and 16 (89%) patients in groups L
      and S, respectively. Premature termination occurred due to patient withdrawal or
      disease progression. No treatment-limiting toxicities occurred in either group.
      The most common toxicity related to the vaccine was grade 1/2 local injection
      site reaction. Induction of Ab3 was observed in all evaluable patients. There
      were no differences between the groups with regard to induction of human anti
      mouse antibody (P = 0.1006). IFNgamma-expressing CA125-specific CD8+ T-cells were
      significantly more frequent in group L, while there was no significant difference
      between CD4+ T-cells in the two groups. CONCLUSIONS: Abagovomab s.c. vaccination
      is safe and well tolerated. The long vaccination schedule tended to be more
      effective with regard to AB3-induction and cellular cytotoxicity.

PMID- 17005632
TI  - Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain
      metastases from malignant melanoma: a phase II DeCOG/ADO study.
AB  - BACKGROUND: Temozolomide has shown some efficacy in metastatic melanoma and
      recently received extended approval to treat brain tumours. The purpose of this
      study was to test a dose-intensified regimen of temozolomide in melanoma patients
      with brain metastases in a prospective, open-label, multicentre phase II trial.
      PATIENTS AND METHODS: Forty-five patients with asymptomatic brain metastases from
      melanoma were stratified into arm A (no prior chemotherapy; n = 21) and arm B
      (previous chemotherapy; n = 24). Patients received oral temozolomide either 150
      mg/m(2)/day (arm A) or 125 mg/m(2)/day (arm B), days 1-7 and 15-21, every 28
      days. The primary study end point was objective response, and secondary end
      points were overall survival and safety. RESULTS: Two patients (4.4%) achieved a
      partial response (PR) in brain metastases (one in each arm), one of them (2.2%)
      also showing a PR in extracerebral disease. An additional five patients (11.1%;
      two in arm A, three in arm B) showed disease stabilisation (SD) in brain and
      other sites. However, 82% revealed progressive disease (PD) already evident 8
      weeks after therapy initiation. Median survival time from therapy onset was 3.5
      months (range 0.7-8.3; arm B) and 4.3 months (range 1.6-11.8; arm A), P = 0.43.
      Dose modifications and prolongations of therapy cycles due to toxicity were
      required in 20% of patients. Grade 3/4 toxicity was observed in one patient only
      (2.2%). CONCLUSIONS: Oral administration of temozolomide given bi-weekly is well
      tolerated in melanoma patients with cerebral involvement. However, the efficacy
      is limited, with lower than 5% objective responses observed in brain and
      extracerebral metastases.

PMID- 17005634
TI  - Relative oral bioavailability of arsenic from contaminated soils measured in the
      cynomolgus monkey.
AB  - A number of studies have found that gastrointestinal absorption of arsenic from
      soil is limited, indicating that a relative oral bioavailability (RBA) adjustment
      is warranted when calculating risks from exposure to arsenic-contaminated soil.
      However, few studies of arsenic bioavailability from soil have been conducted in
      animal models with phylogenetic similarity to humans, such as nonhuman primates.
      We report here the results of a study in which the RBA of arsenic in soil from a
      variety of types of contaminated sites was measured in male cynomolgus monkeys. A
      single oral dose of each contaminated soil was administered to five adult male
      cynomolgus monkeys by gavage, and the extent of oral absorption was evaluated
      through measurement of arsenic recovery in urine and feces. Urinary recovery of
      arsenic following doses of contaminated soil was compared with urinary recovery
      following oral administration of sodium arsenate in water in order to determine
      the RBA of each soil. RBA of arsenic in 14 soil samples from 12 different sites
      ranged from 0.05 to 0.31 (5-31%), with most RBA values in the 0.1-0.2 (10-20%)
      range. The RBA values were found to be inversely related to the amount of arsenic
      present with iron sulfate. No other significant correlations were observed
      between RBA and arsenic mineralogic phases in the test soils. The lack of clear
      relationships between arsenic mineralogy and RBA measured in vivo suggests that
      gastrointestinal absorption of arsenic from soil may be more complex than
      originally thought, and subject to factors other than simple dissolution
      behavior.

PMID- 17005635
TI  - Effects of picornavirus 3A Proteins on Protein Transport and GBF1-dependent COP-I
      recruitment.
AB  - The 3A protein of the coxsackievirus B3 (CVB3), an enterovirus that belongs to
      the family of the picornaviruses, inhibits endoplasmic reticulum-to-Golgi
      transport. Recently, we elucidated the underlying mechanism by showing that CVB3
      3A interferes with ADP-ribosylation factor 1 (Arf1)-dependent COP-I recruitment
      to membranes by binding and inhibiting the function of GBF1, a guanine nucleotide
      exchange factor that is required for the activation of Arf1 (E. Wessels et al.,
      Dev. Cell 11:191-201, 2006). Here, we show that the 3A protein of poliovirus,
      another enterovirus, is also able to interfere with COP-I recruitment through the
      same mechanism. No interference with protein transport or COP-I recruitment was
      observed for the 3A proteins of any of the other picornaviruses tested here
      (human rhinovirus [HRV], encephalomyocarditis virus, foot-and-mouth disease
      virus, and hepatitis A virus). We show that the 3A proteins of HRV, which are the
      most closely related to the enteroviruses, are unable to inhibit COP-I
      recruitment, due to a reduced ability to bind GBF1. When the N-terminal residues
      of the HRV 3A proteins are replaced by those of CVB3 3A, chimeric proteins are
      produced that have gained the ability to bind GBF1 and, by consequence, to
      inhibit protein transport. These results show that the N terminus of the CVB3 3A
      protein is important for binding of GBF1 and its transport-inhibiting function.
      Taken together, our data demonstrate that the activity of the enterovirus 3A
      protein to inhibit GBF1-dependent COP-I recruitment is unique among the
      picornaviruses.

PMID- 17005636
TI  - Efficient reactivation of latent herpes simplex virus from mouse central nervous
      system tissues.
AB  - For decades, numerous ex vivo studies have documented that latent herpes simplex
      virus (HSV) reactivates efficiently from ganglia, but rarely from the central
      nervous systems (CNS), of mice when assayed by mincing tissues before explant
      culture, despite the presence of viral genomes in both sites. Here we show that
      88% of mouse brain stems reactivated latent virus when they were dissociated into
      cell suspensions before ex vivo explant culture. The efficient reactivation of
      HSV from the mouse CNS was demonstrated with more than one viral strain, viral
      serotype, and mouse strain, further indicating that the CNS can be an authentic
      latency site for HSV with the potential to cause recurrent disease.

PMID- 17005637
TI  - Common and specific properties of herpesvirus UL34/UL31 protein family members
      revealed by protein complementation assay.
AB  - The proteins encoded by the UL34 and UL31 genes of herpes simplex virus are
      conserved among herpesviruses. They form a complex that is essential for the
      egress of the herpesvirus nucleocapsids from the nucleus. In previous work on the
      homologous protein complex in murine cytomegalovirus (MCMV), we defined their
      mutual binding domains. Here, we started to map binding domains within the
      UL34/UL31 proteins of alpha-, beta-, and gammaherpesviruses and to locate other
      functional properties. A protein complementation assay (PCA) using the TEM-1 beta
      lactamase fragments fused to UL31 and UL34 protein homologues was used to study
      protein-protein interactions in cells. Wild-type MCMV M50 and M53 provided a
      strong reaction in the PCA, whereas mutants unable to form a complex did not. The
      homologous pairs of herpes simplex virus type 1, pseudorabies virus, human
      cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and murine herpes virus 68
      proteins also reacted, with the exception of the EBV proteins. Cross
      complementation was found to be positive only within the same herpesvirus
      subfamily. Moreover, the HCMV homologues rescued replication-defective MCMV
      genomes lacking one or the other gene. We identified the binding site of M53 for
      M50 in the first conserved region (CR1) (M. Loetzerich, Z. Ruzsics, and U. H.
      Koszinowski, J. Virol. 80:73-84). Here we show that the CR1 of all tested UL31
      proteins contains the UL34 binding site, and chimeric proteins carrying the
      subfamily-specific CR1 rescued the ability to cross-complement in the PCA.

PMID- 17005638
TI  - Generation of filamentous instead of icosahedral particles by repression of
      African swine fever virus structural protein pB438L.
AB  - The mechanisms involved in the construction of the icosahedral capsid of the
      African swine fever virus (ASFV) particle are not well understood at present.
      Capsid formation requires protein p72, the major capsid component, but other
      viral proteins are likely to play also a role in this process. We have examined
      the function of the ASFV structural protein pB438L, encoded by gene B438L, in
      virus morphogenesis. We show that protein pB438L associates with membranes during
      the infection, behaving as an integral membrane protein. Using a recombinant ASFV
      that inducibly expresses protein pB438L, we have determined that this structural
      protein is essential for the formation of infectious virus particles. In the
      absence of the protein, the virus assembly sites contain, instead of icosahedral
      particles, large aberrant tubular structures of viral origin as well as
      bilobulate forms that present morphological similarities with the tubules. The
      filamentous particles, which possess an aberrant core shell domain and an inner
      envelope, are covered by a capsid-like layer that, although containing the major
      capsid protein p72, does not acquire icosahedral morphology. This capsid,
      however, is to some extent functional, as the filamentous particles can move from
      the virus assembly sites to the plasma membrane and exit the cell by budding. The
      finding that, in the absence of protein pB438L, the viral particles formed have a
      tubular structure in which the icosahedral symmetry is lost supports a role for
      this protein in the construction or stabilization of the icosahedral vertices of
      the virus particle.

PMID- 17005640
TI  - Analysis of a new human parechovirus allows the definition of parechovirus types
      and the identification of RNA structural domains.
AB  - Human parechoviruses (HPeV), members of the Parechovirus genus of Picornaviridae,
      are frequent pathogens but have been comparatively poorly studied, and little is
      known of their diversity, evolution, and molecular biology. To increase the
      amount of information available, we have analyzed 7 HPeV strains isolated in
      California between 1973 and 1992. We found that, on the basis of VP1 sequences,
      these fall into two genetic groups, one of which has not been previously
      observed, bringing the number of known groups to five. While these correlate
      partly with the three known serotypes, two members of the HPeV2 serotype belong
      to different genetic groups. In view of the growing importance of molecular
      techniques in diagnosis, we suggest that genotype is an important criterion for
      identifying viruses, and we propose that the genetic groups we have defined
      should be termed human parechovirus types 1 to 5. Complete nucleotide sequence
      analysis of two of the Californian isolates, representing two types, confirmed
      the identification of a new genetic group and suggested a role for recombination
      in parechovirus evolution. It also allowed the identification of a putative HPeV1
      cis-acting replication element, which is located in the VP0 coding region, as
      well as the refinement of previously predicted 5' and 3' untranslated region
      structures. Thus, the results have significantly improved our understanding of
      these common pathogens.

PMID- 17005641
TI  - Nonneutralizing human rhinovirus serotype 2-specific monoclonal antibody 2G2
      attaches to the region that undergoes the most dramatic changes upon release of
      the viral RNA.
AB  - The monoclonal antibody 2G2 has been used extensively for detection and
      quantification of structural changes of human rhinovirus serotype 2 during
      infection. It recognizes exclusively A and B subviral particles, not native
      virus. We have elucidated the basis of this selectivity by determining the
      footprint of 2G2. Since viral escape mutants obviously cannot be obtained, the
      structures of complexes between Fab fragments of 2G2 and 80S subviral B particles
      were determined by cryoelectron microscopy. The footprint of the antibody
      corresponds to the capsid region that we predicted would undergo the most
      dramatic changes upon RNA release.

PMID- 17005639
TI  - Rotavirus infection enhances lipopolysaccharide-induced intussusception in a
      mouse model.
AB  - Unexpected reports of intussusception after vaccination with the live tetravalent
      rotavirus vaccine RotaShield resulted in voluntary withdrawal of the vaccine.
      Intussusception, a condition in which the intestine acutely invaginates upon
      itself, is the most common cause of intestinal obstruction in children. We report
      here the development of a mouse model to study rotavirus-induced intussusception.
      In this model, both homologous murine and heterologous simian rotavirus strains
      significantly enhanced the rate of lipopolysaccharide (LPS)-induced
      intussusception, and this enhancement was replication dependent, requiring
      rotavirus doses of greater than one 50% infectious dose. Rotavirus-induced
      intussusceptions did not have observable lymphoid lead points, despite the
      induction of intestinal lymphoid hyperplasia after rotavirus infection.
      Intussusceptions are also postulated to result from altered intestinal motility,
      but rotavirus infection had no effect on gastrointestinal transit. LPS-induced
      intussusception is associated with the induction of inflammatory mediators, and
      intussusception rates can be modified by inflammatory antagonists. We show that
      rotavirus infection significantly enhanced serum tumor necrosis factor alpha and
      gamma interferon cytokine levels after LPS treatment compared to uninfected mice.
      Together, these data suggest that rotavirus infection sensitized mice to the
      inflammatory effects of subsequent LPS treatment to enhance intussusception
      rates.

PMID- 17005642
TI  - Respiratory syncytial virus F envelope protein associates with lipid rafts
      without a requirement for other virus proteins.
AB  - Like many enveloped viruses, human respiratory syncytial virus (RSV) assembles at
      and buds from lipid rafts. Translocation of the envelope proteins to these
      membrane subdomains is essential for production of infectious virus, but the
      targeting mechanism is poorly understood and it is not known if other virus
      proteins are required. Here we demonstrate that F protein of RSV intrinsically
      targets to lipid rafts without a requirement for any other virus protein,
      including the SH and G envelope proteins. Recombinant virus deficient in SH and G
      but retaining F protein expression was used to demonstrate that F protein still
      localized in rafts in both A549 and HEp-2 cells. Expression of a recombinant F
      gene by use of plasmid vectors demonstrated that F contains its own targeting
      domain and localized to rafts in the absence of other virus proteins. The domain
      responsible for translocation was then mapped. Unlike most other virus envelope
      proteins, F is unusual since the target signal is not contained within the
      cytoplasmic domain nor did it involve fatty acid modified residues. Furthermore,
      exchange of the transmembrane domain with that of the vesicular stomatitis virus
      G protein, a nonraft protein, did not alter F protein raft localization. Taken
      together, these data suggest that domains present in the extracellular portion of
      the protein are responsible for lipid raft targeting of the RSV F protein.

PMID- 17005643
TI  - Helicobacter pylori VacA toxin inhibits human immunodeficiency virus infection of
      primary human T cells.
AB  - Human CD4(+) T cells are major targets for human immunodeficiency virus (HIV)
      infection. Resting T cells are resistant to HIV infection unless activated
      through the T-cell receptor (TCR) or by cytokine signals. How T-cell signaling
      promotes susceptibility of T cells to HIV infection remains poorly understood.
      Here we demonstrate that the VacA toxin produced by Helicobacter pylori can
      inhibit HIV infection of primary T cells, stimulated through the TCR or by
      cytokines alone. This activity of VacA was dependent on its ability to form
      membrane channels. VacA suppressed HIV infection of T cells at a stage after
      viral entry, post-reverse transcription and pre-two-long-terminal-repeat circle
      formation, similar to the cytokine signaling inhibitor rapamycin.
      Mechanistically, neither VacA nor rapamycin inhibited the activation of cytokine
      signal transduction components (STAT5, p42/44 mitogen-activated protein kinase,
      or p38), but both blocked activation of key regulatory proteins required for G(1)
      cell cycle transition. In contrast to rapamycin, VacA did not suppress
      phosphorylation of p70 S6 kinase but caused mitochondrial depolarization and ATP
      depletion within primary T cells. These results suggest that VacA inhibits T-cell
      activation and HIV infection via a novel mechanism. Identifying the host cell
      targets of VacA could be useful for elucidating the HIV life cycle within primary
      T cells.

PMID- 17005644
TI  - Analyses of the interaction between the origin binding domain from simian virus
      40 T antigen and single-stranded DNA provide insights into DNA unwinding and
      initiation of DNA replication.
AB  - DNA helicases are essential for DNA metabolism; however, at the molecular level
      little is known about how they assemble or function. Therefore, as a model for a
      eukaryotic helicase, we are analyzing T antigen (T-ag) the helicase encoded by
      simian virus 40. In this study, nuclear magnetic resonance (NMR) methods were
      used to investigate the transit of single-stranded DNA (ssDNA) through the T-ag
      origin-binding domain (T-ag OBD). When the residues that interact with ssDNA are
      viewed in terms of the structure of a hexamer of the T-ag OBD, comprised of
      residues 131 to 260, they indicate that ssDNA passes over one face of the T-ag
      OBD and then transits through a gap in the open ring structure. The NMR-based
      conclusions are supported by an analysis of previously described mutations that
      disrupt critical steps during the initiation of DNA replication. These and
      related observations are discussed in terms of the threading of DNA through T-ag
      hexamers and the initiation of viral DNA replication.

PMID- 17005645
TI  - In vitro and in vivo fitness of respiratory syncytial virus monoclonal antibody
      escape mutants.
AB  - Respiratory syncytial virus (RSV) is the only infectious disease for which a
      monoclonal antibody (MAb) is used in humans. Palivizumab (PZ) is a humanized
      murine MAb to the F protein of RSV. PZ-resistant viruses appear after in vitro
      and in vivo growth of RSV in the presence of PZ. Fitness for replication could be
      a determinant of the likelihood of dissemination of resistant viruses. We
      assessed the fitness of two PZ-resistant viruses (F212 and MP4). F212 grew less
      well in cell culture than the parent A2 virus and was predicted to be less fit
      than A2. Equal amounts of F212 and A2 were mixed and passaged in cell culture.
      F212 disappeared from the viral population, indicating it was less fit than the
      A2 virus. The MP4 virus grew as well as A2 in culture and in cotton rats. A2/MP4
      virus input ratios of 1:1, 10:1, 100:1, and 1,000:1 were compared in competitive
      replication. For all input ratios except 1,000:1, the MP4 virus became dominant,
      supplanting the A2 virus. The MP4 virus also dominated the A2 virus during growth
      in cotton rats. Thus, the mutant MP4 virus was more fit than A2 virus in both in
      vitro and in vivo competitive replication. Whether this fitness difference was
      due to the identified nucleotide substitutions in the F gene or to mutations
      elsewhere in the genome is unknown. Understanding the mechanisms by which mutant
      virus fitness increased or decreased could prove useful for consideration in
      attenuated vaccine design efforts.

PMID- 17005646
TI  - RhoA-GTPase facilitates entry of Kaposi's sarcoma-associated herpesvirus into
      adherent target cells in a Src-dependent manner.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpesvirus 8) binds to
      adherent target cell surface heparan sulfate molecules via its envelope
      glycoproteins gB and gpK8.1A, to integrins via gB, to the transporter CD98/xCT
      complex, and possibly to another molecule(s). This is followed by virus entry
      overlapping with the induction of preexisting host cell signal pathways, such as
      focal adhesion kinase, Src, phosphatidylinositol 3-kinase (PI3-K), Rho-GTPases,
      protein kinase C-zeta, and extracellular signal-regulated kinase 1/2. Here, using
      hemagglutinin-tagged plasmids expressing wild-type, dominant-positive, and
      dominant-negative forms of RhoA in HEK (human embryonic kidney) 293 cells, we
      investigated the role of RhoA-GTPase in virus entry. The dominant-negative form
      of RhoA GTPase and treatment of target cells with Clostridium difficile toxin B
      (CdTxB), a specific inactivator of Rho-GTPases, significantly blocked KSHV entry.
      KSHV infection induced closely similar levels of FAK and PI3-K in all three cell
      types. In contrast, very strong Src activation was observed in KSHV-infected
      dominant-positive RhoA cells compared to wild-type cells, and only moderate Src
      activation was seen in dominant-negative cells. Inhibition of Src activation by
      CdTxB and reduction of RhoA activation by Src inhibitors suggest that KSHV
      induced Src is involved in RhoA activation, which in turn is involved in a
      feedback-sustained activation of Src. Since the decreased entry in RhoA dominant
      negative cells may be due to inefficient signaling downstream of RhoA, we
      examined the induction of RhoA-activated Dia-2, which is also known to induce
      Src. Dia-2 coimmunoprecipitated with activated Src, which was inhibited by Src
      inhibitors, in the infected cells. Together with the reduced virus entry in RhoA
      dominant-negative cells, these results suggest that activated RhoA-dependent Dia
      2 probably functions as a link between RhoA and Src in KSHV-infected cells,
      mediating the sustained Src activation, and that KSHV-induced Src and RhoA play
      roles in facilitating entry into adherent target cells.

PMID- 17005647
TI  - Hepatitis C virus entry requires a critical postinternalization step and delivery
      to early endosomes via clathrin-coated vesicles.
AB  - Hepatitis C virus (HCV) is a major human pathogen associated with life
      threatening liver disease. Entry into hepatocytes requires CD81 and a putative
      second receptor. In this study, we elucidated the postreceptor attachment stages
      of HCV entry using HCV pseudoparticles (HCVpp) as a model system. By means of
      dominant-negative mutants and short interfering RNAs of various cellular
      proteins, we showed that HCVpp enter via clathrin-coated vesicles and require
      delivery to early but not to late endosomes. However, the kinetics of HCV
      envelope glycoprotein-mediated fusion are delayed compared to those of other
      viruses that enter in early endosomes. Entry of HCVpp can be efficiently blocked
      by bafilomycin A1, which neutralizes the pH in early endosomes and impairs
      progression of endocytosis beyond this stage. However, low-pH exposure of
      bafilomycin A1-treated target cells does not induce entry of HCVpp at the plasma
      membrane or in the early stages of endocytosis. These observations indicate that,
      subsequent to internalization, HCVpp entry necessitates additional, low-pH
      dependent interactions, modifications, or trafficking, and that these events are
      irreversibly disrupted by bafilomycin A1 treatment.

PMID- 17005648
TI  - Retrotransposon suicide: formation of Ty1 circles and autointegration via a
      central DNA flap.
AB  - Despite their evolutionary distance, the Saccharomyces cerevisiae retrotransposon
      Ty1 and retroviruses use similar strategies for replication, integration, and
      interactions with their hosts. Here we examine the formation of circular Ty1 DNA,
      which is comparable to the dead-end circular products that arise during
      retroviral infection. Appreciable levels of circular Ty1 DNA are present with one
      long terminal repeat (LTR) circles and deleted circles comprising major classes,
      while two-LTR circles are enriched when integration is defective. One-LTR circles
      persist when homologous recombination pathways are blocked by mutation,
      suggesting that they result from reverse transcription. Ty1 autointegration
      events readily occur, and many are coincident with and dependent upon DNA flap
      structures that result from DNA synthesis initiated at the central polypurine
      tract. These results suggest that Ty1-specific mechanisms minimize copy number
      and raise the possibility that special DNA structures are a targeting
      determinant.

PMID- 17005649
TI  - Mutational analysis of the lassa virus promoter.
AB  - The promoter sequences directing viral gene expression and genome replication of
      arenaviruses reside within the 3' and 5' termini of each RNA segment. The
      terminal 19 nucleotides at both ends are highly conserved among all arenavirus
      species and are almost completely complementary to each other. This study aimed
      at characterizing the Lassa virus promoter in detail. The relevance of each
      position in the promoter was studied by site-directed mutagenesis using the Lassa
      virus minireplicon system. The data indicate that the Lassa virus promoter
      functions as a duplex, regulates transcription and replication in a coordinated
      manner, and is composed of two functional elements, a sequence-specific region
      from residue 1 to 12 and a variable complementary region from residue 13 to 19.
      The first region appears to interact with the replication complex mainly via base
      specific interactions, while in the second region solely base pairing between 3'
      and 5' promoter ends is important for promoter function.

PMID- 17005650
TI  - Theiler's murine encephalomyelitis virus leader protein amino acid residue 57
      regulates subgroup-specific virus growth on BHK-21 cells.
AB  - Strains of Theiler's murine encephalomyelitis virus (TMEV) are divided into two
      subgroups, TO and GDVII. TMEV strains show subgroup-specific virus growth and
      cell tropism and induce subgroup-specific diseases. Using site-directed
      mutagenesis, we demonstrated that the amino acid at position 57 of the leader
      protein (L(57)), which is located at the most N-terminal part of the polyprotein,
      regulates subgroup-specific virus growth on BHK-21 cells. Further study suggested
      that L(57) may regulate viral RNA encapsidation, although it does not affect the
      synthesis of viral proteins or the assembly of viral intermediates.

PMID- 17005651
TI  - Role of ran binding protein 5 in nuclear import and assembly of the influenza
      virus RNA polymerase complex.
AB  - The influenza A virus RNA-dependent RNA polymerase is a heterotrimeric complex of
      polymerase basic protein 1 (PB1), PB2, and polymerase acidic protein (PA)
      subunits. It performs transcription and replication of the viral RNA genome in
      the nucleus of infected cells. We have identified a nuclear import factor, Ran
      binding protein 5 (RanBP5), also known as karyopherin beta3, importin beta3, or
      importin 5, as an interactor of the PB1 subunit. RanBP5 interacted with either
      PB1 alone or with a PB1-PA dimer but not with a PB1-PB2 dimer or the trimeric
      complex. The interaction between RanBP5 and PB1-PA was disrupted by RanGTP in
      vitro, allowing PB2 to bind to the PB1-PA dimer to form a functional trimeric RNA
      polymerase complex. We propose a model in which RanBP5 acts as an import factor
      for the newly synthesized polymerase by targeting the PB1-PA dimer to the
      nucleus. In agreement with this model, small interfering RNA (siRNA)-mediated
      knock-down of RanBP5 inhibited the nuclear accumulation of the PB1-PA dimer.
      Moreover, siRNA knock-down of RanBP5 resulted in the delayed accumulation of
      viral RNAs in infected cells, confirming that RanBP5 plays a biological role
      during the influenza virus life cycle.

PMID- 17005652
TI  - Modulation of DNA vaccine-elicited CD8+ T-lymphocyte epitope immunodominance
      hierarchies.
AB  - Generating broad cellular immune responses against a diversity of viral epitopes
      is a major goal of current vaccine strategies for human immunodeficiency virus
      type 1 (HIV-1) and other pathogens. Virus-specific CD8(+) T-lymphocyte responses,
      however, are often highly focused on a very limited number of immunodominant
      epitopes. For an HIV-1 vaccine, the breadth of CD8(+) T-lymphocyte responses may
      prove to be critical as a result of the need to cover a wide diversity of viral
      isolates in the population and to limit viral escape from dominant epitope
      specific T lymphocytes. Here we show that epitope modification strategies can
      alter CD8(+) T-lymphocyte epitope immunodominance hierarchies elicited by a DNA
      vaccine in mice. Mice immunized with a DNA vaccine expressing simian
      immunodeficiency virus Gag lacking the dominant D(b)-restricted AL11 epitope
      generated a marked and durable augmentation of responses specific for the
      subdominant D(b)-restricted KV9 epitope. Moreover, anatomic separation strategies
      and heterologous prime-boost regimens generated codominant responses against both
      epitopes. These data demonstrate that dominant epitopes can dramatically suppress
      the immunogenicity of subdominant epitopes in the context of gene-based vaccines
      and that epitope modification strategies can be utilized to enhance responses to
      subdominant epitopes.

PMID- 17005653
TI  - Infectious RNA isolated from the spinal cords of mice chronically infected with
      Theiler's murine encephalomyelitis virus.
AB  - The DA strain of Theiler's murine encephalomyelitis virus (TMEV) persistently
      infects cells of the spinal cord during the chronic phase of infection. Although
      in situ hybridization and reverse transcription-PCR have demonstrated the
      presence of viral RNA in the spinal cord, it has not been determined whether this
      RNA is infectious and, if so, how many PFU equivalents of virus the RNA can
      yield. In this study, we demonstrated that TMEV RNA isolated from the spinal
      cords of chronically infected mice is infectious and that there is at least 30
      fold more infectious RNA than infectious virus in the spinal cords of these mice.

PMID- 17005654
TI  - Divergences in protein activity and cellular localization within the Campoletis
      sonorensis Ichnovirus Vankyrin family.
AB  - Ichnoviruses (IVs) occur in obligate symbiotic associations with endoparasitic
      ichneumonid wasps. IVs are injected with eggs during parasitization, where viral
      infection and gene expression alter host physiology to ensure endoparasitoid
      survival. The seven Campoletis sonorensis IV (CsIV) vankyrin genes encode
      proteins that possess ankyrin repeat domains resembling the inhibitory domains of
      NF-kappaB transcription factor inhibitors (IkappaBs). The CsIV vankyrins are
      divided into two subclasses: those expressed primarily in the host fat body
      (three genes) and those expressed in host hemocytes (four genes). CsIV vankyrin
      proteins showed limited antigenic similarity when analyzed by Western blotting.
      Cellular localization and expression patterns of recombinant vankyrin proteins in
      High Five and Sf9 insect cells differed within and between the subclasses and in
      cells exposed to lipopolysaccharide, laminarin, or viral immune challenge. In
      unstimulated Sf9 cells, five vankyrins were detected in cell nuclei. The
      remaining two proteins localized predominantly to cytoplasmic granules. Immune
      stimulation of cells resulted in a nuclear-to-cytoplasmic shift of three
      vankyrins but did not affect localization of other variants. When expressed from
      recombinant Autographa californica multiple nucleopolyhedroviruses (AcMNPVs), all
      vankyrins showed a nuclear localization during early stages of infection with
      patterns resembling those of immune-challenged cells as the infection progressed.
      Two fat body vankyrins also produced unique biological effects when expressed
      from recombinant AcMNPV. Insect cells infected with these viruses exhibited
      enhanced longevity compared to those infected with viruses expressing other
      vankyrins. Together, these data suggest that vankyrin proteins in CsIV have
      divergent physiological functions.

PMID- 17005655
TI  - Reovirus mu1 structural rearrangements that mediate membrane penetration.
AB  - Membrane penetration by nonenveloped reoviruses is mediated by the outer-capsid
      protein, mu1 (76 kDa). Previous evidence has suggested that an autolytic cleavage
      in mu1 allows the release of its N-terminally myristoylated peptide, mu1N (4
      kDa), which probably then interacts with the target-cell membrane. A substantial
      rearrangement of the remaining portion of mu1, mu1C (72 kDa), must also have
      occurred for mu1N to be released, and some regions in mu1C may make additional
      contacts with the membrane. We describe here a particle-free system to study
      conformational rearrangements of mu1. We show that removal of the protector
      protein sigma3 is not sufficient to trigger rearrangement of free mu1 trimer and
      that free mu1 trimer undergoes conformational changes similar to those of
      particle-associated mu1 when induced by similar conditions. The mu1
      rearrangements require separation of the mu1 trimer head domains but not the
      mu1N/C autocleavage. We have also obtained a relatively homogeneous form of the
      structurally rearranged mu1 (mu1*) in solution. It is an elongated monomer and
      retains substantial alpha-helix content. We have identified a protease-resistant
      approximately 23-kDa fragment of mu1*, which contains the largely alpha-helical
      regions designated domains I and II in the conformation of mu1 prior to
      rearrangement. We propose that the mu1 conformational changes preceding membrane
      penetration or disruption during cell entry involve (i) separation of the beta
      barrel head domains in the mu1 trimer, (ii) autolytic cleavage at the mu1N/C
      junction, associated with partial unfolding of mu1C and release of mu1N, and
      (iii) refolding of the N-terminal helical domains of mu1C, with which mu1N was
      previously complexed, accompanied by dissociation of the mu1 trimer.

PMID- 17005656
TI  - In vivo packaging of brome mosaic virus RNA3, but not RNAs 1 and 2, is dependent
      on a cis-acting 3' tRNA-like structure.
AB  - The four encapsidated RNAs of brome mosaic virus (BMV; B1, B2, B3, and B4)
      contain a highly conserved 3' 200-nucleotide (nt) region encompassing the tRNA
      like structure (TLS) which is required for packaging in vitro (Y. G. Choi, T. W.
      Dreher, and A. L. N. Rao, Proc. Natl. Acad. Sci. USA 99:655-660, 2002). To
      validate these observations in vivo, we performed packaging assays using
      Agrobacterium-mediated transient expression of RNAs and coat protein (CP) (P.
      Annamalai and A. L. N. Rao, Virology 338:96-111, 2005). Coexpression of TLS-less
      constructs of B1 or B2 or B3 and CP mRNAs in Nicotiana benthamiana leaves
      resulted in packaging of TLS-less B1 and B2 but not B3, suggesting that packaging
      of B3 requires the TLS in cis. This conjecture was confirmed by the efficient
      packaging of a B3 chimera in which the viral TLS was replaced with a cellular
      tRNA(Tyr). When N. benthamiana leaves were infiltrated with a mixture of
      transformants containing wild-type B1 (wtB1) plus wtB2 plus a TLS-less B3
      (wtB1+wtB2+TLS-lessB3), the 3' end of progeny B3 was restored by heterologous
      recombination with that of either B1 or B2. This intrinsic cis-requirement of TLS
      in promoting B3 packaging was further confirmed when a mixture containing
      agrotransformants of TLS-less B1+B2+B3 was supplemented with either wtB4 or a 3'
      200-nt or 3' 336-nt untranslated region (UTR) of B3. Northern blot analysis
      followed by sequencing of B3 progeny revealed that replication of TLS-less B3,
      but not TLS-less B1 or B2, was fully restored due to recombination with TLS from
      transiently expressed wtB4 or the B3 3' UTR. Collectively, these observations
      suggested that the requirement of a cis-acting TLS is distinct for B3 compared
      with B1 or B2.

PMID- 17005657
TI  - Access to nectin favors herpes simplex virus infection at the apical surface of
      polarized human epithelial cells.
AB  - Viral entry may preferentially occur at the apical or the basolateral surfaces of
      polarized cells, and differences may impact pathogenesis, preventative
      strategies, and successful implementation of viral vectors for gene therapy. The
      objective of these studies was to examine the polarity of herpes simplex virus
      (HSV) entry using several different human epithelial cell lines. Human uterine
      (ECC-1), colonic (CaCo-2), and retinal pigment (ARPE-19) epithelial cells were
      grown on collagen-coated inserts, and the polarity was monitored by measuring the
      transepithelial cell resistance. Controls were CaSki cells, a human cervical cell
      line that does not polarize in vitro. The polarized cells, but not CaSki cells,
      were 16- to 50-fold more susceptible to HSV infection at the apical surface than
      at the basolateral surface. Disruption of the tight junctions by treatment with
      EGTA overcame the restriction on basolateral infection but had no impact on
      apical infection. No differences in binding at the two surfaces were observed.
      Confocal microscopy demonstrated that nectin-1, the major coreceptor for HSV
      entry, sorted preferentially to the apical surface, overlapping with adherens and
      tight junction proteins. Transfection with small interfering RNA specific for
      nectin-1 resulted in a significant reduction in susceptibility to HSV at the
      apical surface but had little impact on basolateral infection. Infection from the
      apical but not the basolateral surface triggered focal adhesion kinase
      phosphorylation and led to nuclear transport of viral capsids and viral gene
      expression. These studies indicate that access to nectin-1 contributes to
      preferential apical infection of these human epithelial cells by HSV.

PMID- 17005658
TI  - Inhibition of influenza virus infection by a novel antiviral peptide that targets
      viral attachment to cells.
AB  - Influenza A viruses continue to cause widespread morbidity and mortality. There
      is an added concern that the highly pathogenic H5N1 influenza A viruses,
      currently found throughout many parts of the world, represent a serious public
      health threat and may result in a pandemic. Intervention strategies to halt an
      influenza epidemic or pandemic are a high priority, with an emphasis on vaccines
      and antiviral drugs. In these studies, we demonstrate that a 20-amino-acid
      peptide (EB, for entry blocker) derived from the signal sequence of fibroblast
      growth factor 4 exhibits broad-spectrum antiviral activity against influenza
      viruses including the H5N1 subtype in vitro. The EB peptide was protective in
      vivo, even when administered postinfection. Mechanistically, the EB peptide
      inhibits the attachment to the cellular receptor, preventing infection. Further
      studies demonstrated that the EB peptide specifically binds to the viral
      hemagglutinin protein. This novel peptide has potential value as a reagent to
      study virus attachment and as a future therapeutic.

PMID- 17005659
TI  - Characterization of a novel 5' subgenomic RNA3a derived from RNA3 of Brome mosaic
      bromovirus.
AB  - The synthesis of 3' subgenomic RNA4 (sgRNA4) by initiation from an internal sg
      promoter in the RNA3 segment was first described for Brome mosaic bromovirus
      (BMV), a model tripartite positive-sense RNA virus (W. A. Miller, T. W. Dreher,
      and T. C. Hall, Nature 313:68-70, 1985). In this work, we describe a novel 5'
      sgRNA of BMV (sgRNA3a) that we propose arises by premature internal termination
      and that encapsidates in BMV virions. Cloning and sequencing revealed that,
      unlike any other BMV RNA segment, sgRNA3a carries a 3' oligo(A) tail, in which
      respect it resembles cellular mRNAs. Indeed, both the accumulation of sgRNA3a in
      polysomes and the synthesis of movement protein 3a in in vitro systems suggest
      active functions of sgRNA3a during protein synthesis. Moreover, when copied in
      the BMV replicase in vitro reaction, the minus-strand RNA3 template generated the
      sgRNA3a product, likely by premature termination at the minus-strand oligo(U)
      tract. Deletion of the oligo(A) tract in BMV RNA3 inhibited synthesis of sgRNA3a
      during infection. We propose a model in which the synthesis of RNA3 is terminated
      prematurely near the sg promoter. The discovery of 5' sgRNA3a sheds new light on
      strategies viruses can use to separate replication from the translation functions
      of their genomic RNAs.

PMID- 17005660
TI  - Identification of an essential domain in the herpesvirus VP1/2 tegument protein:
      the carboxy terminus directs incorporation into capsid assemblons.
AB  - The herpesvirus tegument is a layer of viral and cellular proteins located
      between the capsid and envelope of the virion. The VP1/2 tegument protein is
      critical for the propagation of all herpesviruses examined. Using an infectious
      clone of the alphaherpesvirus pseudorabies virus, we have made a collection of
      truncation and in-frame deletion mutations within the VP1/2 gene (UL36) and
      examined the resulting viruses for spread between cells. We found that the
      majority of the VP1/2 protein either was essential for virus propagation or did
      not tolerate large deletions. A recently described amino-terminal deubiquitinase
      encoding domain was dispensable for alphaherpesvirus propagation, but the rate of
      propagation in an epithelial cell line and the frequency of transport in axons of
      primary sensory neurons were both reduced. We mapped one essential domain to a
      conserved sequence at the VP1/2 carboxy terminus and demonstrated that this
      domain sufficient to redirect the green fluorescent protein to capsid assemblons
      in nuclei of infected cells.

PMID- 17005661
TI  - Mutation of YMYL in the Nipah virus matrix protein abrogates budding and alters
      subcellular localization.
AB  - Matrix (M) proteins reportedly direct the budding of paramyxoviruses from
      infected cells. In order to begin to characterize the assembly process for the
      highly lethal, emerging paramyxovirus Nipah virus (NiV), we have examined the
      budding of NiV M. We demonstrated that expression of the NiV M protein is
      sufficient to produce budding virus-like particles (VLPs) that are physically and
      morphologically similar to NiV. We identified in NiV M a sequence, YMYL, with
      similarity to the YPDL late domain found in the equine infectious anemia virus
      Gag protein. When the YMYL within NiV M was mutated, VLP release was abolished
      and M was relocalized to the nucleus, but the mutant M proteins retained
      oligomerization activity. When YMYL was fused to a late-domain mutant of the
      Ebola virus VP40 matrix protein, VP40 budding was restored. These results suggest
      that the YMYL sequence may act as a trafficking signal and a late domain for NiV
      M.

PMID- 17005662
TI  - Induction of robust immune responses against human immunodeficiency virus is
      supported by the inherent tropism of adeno-associated virus type 5 for dendritic
      cells.
AB  - The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors
      expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to
      induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a
      higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2
      vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1,
      AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An
      immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8
      vectors expressing the Env gp160 gene induced higher HIV-specific humoral and
      cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector
      producing the best responses. Furthermore, mice injected with DCs that had been
      transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher
      HIV-specific cell-mediated immune responses than did DCs transduced with AAV1 and
      AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect
      cells elicit similar levels of antigen-specific immune responses. These results
      demonstrate that the immunogenicity of AAV vectors depends on their tropism for
      both antigen-presenting cells (such as DCs) and non-antigen-presenting cells
      (such as muscular cells) and that AAV5 is a better vector than other AAV
      serotypes. These results may aid in the development of AAV-based vaccine and gene
      therapy.

PMID- 17005663
TI  - Diminished production of monocyte proinflammatory cytokines during human
      immunodeficiency virus viremia is mediated by type I interferons.
AB  - The effect of human immunodeficiency virus (HIV) infection and high-level HIV
      replication on the function of monocytes was investigated. HIV-positive patients
      had elevated levels of spontaneous production of some or all of the monocyte
      proinflammatory cytokines measured (interleukin-1beta [IL-1beta], IL-6, and tumor
      necrosis factor alpha [TNF-alpha]) compared to uninfected controls. In patients
      on therapy with high frequencies of monocytes producing proinflammatory
      cytokines, this frequency was diminished in the context of viremia during an
      interruption of therapy. Diminished production of proinflammatory cytokines
      during viremia was restored by culture with autologous CD4(+) T cells or
      monocytes from an on-therapy time point or lipopolysaccharide (LPS). Microarray
      analysis demonstrated that diminished monocyte production of proinflammatory
      cytokines was correlated with elevated type I interferon-stimulated gene
      transcripts. The addition of exogenous alpha 2A interferon diminished the
      spontaneous production of IL-1beta, IL-6, and TNF-alpha but did not affect
      responses to LPS, recapitulating the changes observed for HIV-viremic patients.
      These results suggest that monocyte function is diminished during high-level HIV
      viremia and that this effect is mediated by chronic stimulation by type I
      interferons. This effect on monocytes during viremia may play a role in
      diminished innate or adaptive immune system functions in HIV-infected patients.
      In addition, the restoration of these functions may also play a role in some
      immune reconstitution syndromes observed during initiation of therapy.

PMID- 17005664
TI  - Feline model of acute nipah virus infection and protection with a soluble
      glycoprotein-based subunit vaccine.
AB  - Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing
      considerable morbidity and mortality in a number of mammalian species, including
      humans. Case reports from outbreaks and previous challenge experiments have
      suggested that cats were highly susceptible to NiV infection, responding with a
      severe respiratory disease and systemic infection. Here we have assessed the cat
      as a model of experimental NiV infection and use it in the evaluation of a
      subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult
      cats each were inoculated subcutaneously with either 500 or 5,000 50% tissue
      culture infective dose(s) (TCID(50)) of NiV. Animals were monitored closely for
      disease onset, and extensive analysis was conducted on samples and tissues taken
      during infection and at necropsy to determine viral load and tissue tropism. All
      animals developed clinical disease 6 to 9 days postinfection, a finding
      consistent with previous observations. In a subsequent experiment, two cats were
      immunized with HeV sG and two were immunized with NiV sG. Homologous serum
      neutralizing titers were greater than 1:20,000, and heterologous titers were
      greater than 1:20,000 to 16-fold lower. Immunized animals and two additional
      naive controls were then challenged subcutaneously with 500 TCID(50) of NiV.
      Naive animals developed clinical disease 6 to 13 days postinfection, whereas none
      of the immunized animals showed any sign of disease. TaqMan PCR analysis of
      samples from naive animals revealed considerable levels of NiV genome in a wide
      range of tissues, whereas the genome was evident in only two immunized cats in
      only four samples and well below the limit of accurate detection. These results
      indicate that the cat provides a consistent model for acute NiV infection and
      associated pathogenesis and an effective subunit vaccine strategy appears
      achievable.

PMID- 17005665
TI  - Preferential translation of vesicular stomatitis virus mRNAs is conferred by
      transcription from the viral genome.
AB  - Host protein synthesis is inhibited in cells infected with vesicular stomatitis
      virus (VSV). It has been proposed that viral mRNAs are subjected to the same
      inhibition but are predominantly translated because of their abundance. To
      compare translation efficiencies of viral and host mRNAs during infection, we
      used an enhanced green fluorescent protein (EGFP) reporter expressed from a
      recombinant virus or from the host nucleus in stably transfected cells.
      Translation efficiency of host-derived EGFP mRNA was reduced more than threefold
      at eight hours postinfection, while viral-derived mRNA was translated around
      sevenfold more efficiently than host-derived EGFP mRNA in VSV-infected cells. To
      test whether mRNAs transcribed in the cytoplasm are resistant to shutoff of
      translation during VSV infection, HeLa cells were infected with a recombinant
      simian virus 5 (rSV5) that expressed GFP. Cells were then superinfected with VSV
      or mock superinfected. GFP mRNA transcribed by rSV5 was not resistant to
      translation inhibition during superinfection with VSV, indicating that
      transcription in the cytoplasm is not sufficient for preventing translation
      inhibition. To determine if cis-acting sequences in untranslated regions (UTRs)
      were involved in preferential translation of VSV mRNAs, we constructed EGFP
      reporters with VSV or control UTRs and measured the translation efficiency in
      mock-infected and VSV-infected cells. The presence of VSV UTRs did not affect
      mRNA translation efficiency in mock- or VSV-infected cells, indicating that VSV
      mRNAs do not contain cis-acting sequences that influence translation. However, we
      found that when EGFP mRNAs transcribed by VSV or by the host were translated in
      vitro, VSV-derived EGFP mRNA was translated 22 times more efficiently than host
      derived EGFP mRNA. This indicated that VSV mRNAs do contain cis-acting structural
      elements (that are not sequence based), which enhance translation efficiency of
      viral mRNAs.

PMID- 17005666
TI  - Preclinical model to test human papillomavirus virus (HPV) capsid vaccines in
      vivo using infectious HPV/cottontail rabbit papillomavirus chimeric
      papillomavirus particles.
AB  - A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs)
      was recently approved for human use. It is generally assumed that VLP vaccines
      protect by inducing type-specific neutralizing antibodies. Preclinical animal
      models cannot be used to test for protection against HPV infections due to
      species restriction. We developed a model using chimeric HPV capsid/cottontail
      rabbit papillomavirus (CRPV) genome particles to permit the direct testing of HPV
      VLP vaccines in rabbits. Animals vaccinated with CRPV, HPV type 16 (HPV-16), or
      HPV-11 VLPs were challenged with both homologous (CRPV capsid) and chimeric (HPV
      16 capsid) particles. Strong type-specific protection was observed, demonstrating
      the potential application of this approach.

PMID- 17005667
TI  - Visualization of alpha-helices in a 6-angstrom resolution cryoelectron microscopy
      structure of adenovirus allows refinement of capsid protein assignments.
AB  - The structure of adenovirus was determined to a resolution of 6 A by cryoelectron
      microscopy (cryoEM) single-particle image reconstruction. Docking of the hexon
      and penton base crystal structures into the cryoEM density established that alpha
      helices of 10 or more residues are resolved as rods. A difference map was
      calculated by subtracting a pseudoatomic capsid from the cryoEM reconstruction.
      The resulting density was analyzed in terms of observed alpha-helices and
      secondary structure predictions for the additional capsid proteins that currently
      lack atomic resolution structures (proteins IIIa, VI, VIII, and IX). Protein
      IIIa, which is predicted to be highly alpha-helical, is assigned to a cluster of
      helices observed below the penton base on the inner capsid surface. Protein VI is
      present in approximately 1.5 copies per hexon trimer and is predicted to have two
      long alpha-helices, one of which appears to lie inside the hexon cavity. Protein
      VIII is cleaved by the adenovirus protease into two fragments of 7.6 and 12.1
      kDa, and the larger fragment is predicted to have one long alpha-helix, in
      agreement with the observed density for protein VIII on the inner capsid surface.
      Protein IX is predicted to have one long alpha-helix, which also has a strongly
      indicated propensity for coiled-coil formation. A region of density near the
      facet edge is now resolved as a four-helix bundle and is assigned to four copies
      of the C-terminal alpha-helix from protein IX.

PMID- 17005668
TI  - Evidence for CDK-dependent and CDK-independent functions of the murine
      gammaherpesvirus 68 v-cyclin.
AB  - Gamma-2 herpesviruses encode homologues of mammalian D-type cyclins (v-cyclins),
      which likely function to manipulate the cell cycle, thereby providing a cellular
      environment conducive to virus replication and/or reactivation from latency. We
      have previously shown that the v-cyclin of murine gammaherpesvirus 68 is an
      oncogene that binds and activates cellular cyclin-dependent kinases (CDKs) and is
      required for efficient reactivation from latency. To determine the contribution
      of v-cyclin-mediated cell cycle regulation to the viral life cycle, recombinant
      viruses in which specific point mutations (E133V or K104E) were introduced into
      the v-cyclin open reading frame were generated, resulting in the disruption of
      CDK binding and activation. While in vitro growth of these mutant viruses was
      unaffected, lytic replication in the lungs following low-dose intranasal
      inoculation was attenuated for both mutants deficient in CDK binding as well as
      virus in which the entire v-cyclin open reading frame was disrupted by the
      insertion of a translation termination codon. This replication defect was not
      apparent in spleens of mice following intraperitoneal inoculation, suggesting a
      cell type- and/or route-specific dependence on v-cyclin-CDK interactions during
      the acute phase of virus infection. Notably, although a v-cyclin-null virus was
      highly attenuated for reactivation from latency, the E133V v-cyclin CDK-binding
      mutant exhibited only a modest defect in virus reactivation from splenocytes, and
      neither the E133V nor K104E v-cyclin mutants were compromised in reactivation
      from peritoneal exudate cells. Taken together, these data suggest that lytic
      replication and reactivation in vivo are differentially regulated by CDK
      dependent and CDK-independent functions of v-cyclin, respectively.

PMID- 17005669
TI  - Human cytomegalovirus blocks tumor necrosis factor alpha- and interleukin-1beta
      mediated NF-kappaB signaling.
AB  - NF-kappaB plays an important role in the early cellular response to pathogens by
      activating genes involved in inflammation, immune response, and cell
      proliferation and survival. NF-kappaB is also utilized by many viral pathogens,
      like human cytomegalovirus (HCMV), to activate their own gene expression
      programs, reflecting intricate roles for NF-kappaB in both antiviral defense
      mechanisms and viral physiology. Here we show that the NF-kappaB signaling
      pathway stimulated by proinflammatory cytokines tumor necrosis factor alpha (TNF
      alpha) and interleukin-1beta (IL-1beta) becomes inhibited in HCMV-infected cells.
      The block to NF-kappaB signaling is first noticeable during the early phase of
      infection but is fully established only at later times. Biochemical and genetic
      evidence demonstrates that the viral inhibition of proinflammatory signaling by
      distinct cytokines occurs upstream of the convergence point of NF-kappaB
      activating pathways, i.e., the IkappaB kinase complex, and that it is mediated
      via different mechanisms. Consistent with this, we further show that an HCMV
      variant that has lost the ability to downregulate TNF-alpha-induced NF-kappaB
      signaling also fails to downregulate surface expression of TNF receptor 1,
      thereby mechanistically linking the inhibition of TNF-alpha-induced NF-kappaB
      signaling by HCMV to TNF receptor targeting. Our data support a model whereby
      HCMV inhibits cytokine-induced NF-kappaB signaling at later times during
      infection, and we suggest that this contributes to the inhibition of the cell's
      antiviral defense program.

PMID- 17005670
TI  - JC virus evolution and its association with human populations.
AB  - The ubiquitous human polyomavirus JC (JCV) is a small double-stranded DNA virus
      that establishes a persistent infection, and it is often transmitted from parents
      to children. There are at least 14 subtypes of the virus associated with
      different human populations. Because of its presumed codivergence with humans,
      JCV has been used as a genetic marker for human evolution and migration.
      Codivergence has also been used as a basis for estimating the rate of nucleotide
      substitution in JCV. We tested the hypothesis of host-virus codivergence by (i)
      performing a reconciliation analysis of phylogenetic trees of human and JCV
      populations and (ii) providing the first estimate of the evolutionary rate of JCV
      that is independent from the assumption of codivergence. Strikingly, our
      comparisons of JCV and human phylogenies provided no evidence for codivergence,
      suggesting that this virus should not be used as a marker for human population
      history. Further, while the estimated nucleotide substitution rate of JCV has
      large confidence intervals due to limited sampling, our analysis suggests that
      this virus may evolve nearly two orders of magnitude faster than predicted under
      the codivergence hypothesis.

PMID- 17005671
TI  - Growth transformation of human T cells by herpesvirus saimiri requires multiple
      Tip-Lck interaction motifs.
AB  - Lymphoma induction and T-cell transformation by herpesvirus saimiri strain C488
      depends on two viral oncoproteins, StpC and Tip. The major interaction partner of
      Tip is the protein tyrosine kinase Lck, a key regulator of T-cell activation. The
      Lck binding domain (LBD) of Tip comprises two interaction motifs, a proline-rich
      SH3 domain-binding sequence (SH3B) and a region with homology to the C terminus
      of Src family kinase domains (CSKH). In addition, biophysical binding analyses
      with purified Lck-SH2 domain suggest the phosphorylated tyrosine residue 127 of
      Tip (pY127) as a potential third Lck interaction site. Here, we addressed the
      relevance of the individual binding motifs, SH3B, CSKH, and pY127, for Tip-Lck
      interaction and for human T-cell transformation. Both motifs within the LBD
      displayed Lck binding activities and cooperated to achieve a highly efficient
      interaction, while pY127, the major tyrosine phosphorylation site of Tip, did not
      enhance Lck binding in T cells. Herpesvirus saimiri strain C488 recombinants
      lacking one or both LBD motifs of Tip lost their transforming potential on human
      cord blood lymphocytes. Recombinant virus expressing Tip with a mutation at
      position Y127 was still able to transform human T lymphocytes but, in contrast to
      wild-type virus, was strictly dependent on exogenous interleukin-2. Thus, the
      strong Lck binding mediated by cooperation of both LBD motifs was essential for
      the transformation of human T cells by herpesvirus saimiri C488. The major
      tyrosine phosphorylation site Y127 of Tip was particularly required for
      transformation in the absence of exogenous interleukin-2, suggesting its
      involvement in cytokine signaling pathways.

PMID- 17005672
TI  - Induction of innate immunity against herpes simplex virus type 2 infection via
      local delivery of Toll-like receptor ligands correlates with beta interferon
      production.
AB  - Toll-like receptors (TLRs) constitute a family of innate receptors that recognize
      and respond to a wide spectrum of microorganisms, including fungi, bacteria,
      viruses, and protozoa. Previous studies have demonstrated that ligands for TLR3
      and TLR9 induce potent innate antiviral responses against herpes simplex virus
      type 2 (HSV-2). However, the factor(s) involved in this innate protection is not
      well-defined. Here we report that production of beta interferon (IFN-beta) but
      not production of IFN-alpha, IFN-gamma, or tumor necrosis factor alpha (TNF
      alpha) strongly correlates with innate protection against HSV-2. Local delivery
      of poly(I:C) and CpG oligodeoxynucleotides induced significant production of IFN
      beta in the genital tract and provided complete protection against intravaginal
      (IVAG) HSV-2 challenge. There was no detectable IFN-beta in mice treated with
      ligands for TLR4 or TLR2, and these mice were not protected against subsequent
      IVAG HSV-2 challenge. There was no correlation between levels of TNF-alpha or IFN
      gamma in the genital tract and protection against IVAG HSV-2 challenge following
      TLR ligand delivery. Both TNF-alpha(-/-) and IFN-gamma(-/-) mice were protected
      against IVAG HSV-2 challenge following local delivery of poly(I:C). To confirm
      that type I interferon, particularly IFN-beta, mediates innate protection, mice
      unresponsive to type I interferons (IFN-alpha/betaR(-/-) mice) and mice lacking
      IFN regulatory factor-3 (IRF-3(-/-) mice) were treated with poly(I:C) and then
      challenged with IVAG HSV-2. There was no protection against HSV-2 infection
      following poly(I:C) treatment of IFN-alpha/betaR(-/-) or IRF-3(-/-) mice. Local
      delivery of murine recombinant IFN-beta protected C57BL/6 and IRF-3(-/-) mice
      against IVAG HSV-2 challenge. Results from these in vivo studies clearly suggest
      a strong correlation between IFN-beta production and innate antiviral immunity
      against HSV-2.

PMID- 17005673
TI  - Repression of HMGA2 gene expression by human cytomegalovirus involves the IE2 86
      kilodalton protein and is necessary for efficient viral replication and
      inhibition of cyclin A transcription.
AB  - Human cytomegalovirus (HCMV) infection results in dysregulation of several cell
      cycle genes, including inhibition of cyclin A transcription. In this work, we
      examine the effect of the HCMV infection on expression of the high-mobility group
      A2 (HMGA2) gene, which encodes an architectural transcription factor that is
      involved in cyclin A promoter activation. We find that expression of HMGA2 RNA is
      repressed in infected cells. To determine whether repression of HMGA2 is directly
      related to the inhibition of cyclin A expression and impacts on the progression
      of the infection, we constructed an HCMV recombinant that expressed HMGA2. In
      cells infected with the recombinant virus, cyclin A mRNA and protein are induced,
      and there is a significant delay in viral early gene expression and DNA
      replication. To determine the mechanism of HMGA2 repression, we used recombinant
      viruses that expressed either no IE1 72-kDa protein (CR208) or greatly reduced
      levels of IE2 86-kDa (IE2 86) protein (IE2 86DeltaSX-EGFP). At a high
      multiplicity of infection, the IE1 deletion mutant is comparable to the wild type
      with respect to inhibition of HMGA2. In contrast, the IE2 86DeltaSX-EGFP mutant
      does not significantly repress HMGA2 expression, suggesting that IE2 86 is
      involved in the regulation of this gene. Cyclin A expression is also induced in
      cells infected with this mutant virus. Since HMGA2 is important for cell
      proliferation and differentiation, particularly during embryogenesis, it is
      possible that the repression of HMGA2 expression during fetal development could
      contribute to the specific birth defects in HCMV-infected neonates.

PMID- 17005674
TI  - Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal
      adenylyltransferase activity.
AB  - The RNA-dependent RNA polymerase nsP4 is an integral part of the alphavirus
      replication complex. To define the role of nsP4 in viral RNA replication and for
      a structure-function analysis, we expressed Sindbis virus nsP4 in Escherichia
      coli. The core catalytic domain of nsP4 (Delta97nsP4, a deletion of the N
      terminal 97 amino acids), which consists of the predicted polymerase domain
      containing the GDD amino acid motif required for viral RNA synthesis, was stable
      against proteolytic degradation during expression. Therefore, the recombinant
      core domain and selected mutants were expressed and purified to homogeneity. We
      determined that Delta97nsP4 possesses terminal adenylyltransferase (TATase)
      activity, as it specifically catalyzed the addition of adenine to the 3' end of
      an acceptor RNA in the presence of divalent cations. Furthermore, Delta97nsP4 is
      unable to transfer other nucleotides (UTP, CTP, GTP, and dATP) to the acceptor
      RNA in the absence or presence of other nucleotides. Delta97nsP4 possessing a GDD
      to-GAA mutation completely inactivates the enzymatic activity. However, a GDD-to
      SNN mutation did not inactivate the enzyme but reduced its activity to
      approximately 45% of that of the wild type in the presence of Mg(2+).
      Investigation of the TATase of the GDD-to-SNN mutant revealed that it had TATase
      equivalent to that of the wild type in the presence of Mn(2+). Identification of
      Delta97nsP4 TATase activity suggests a novel function of the alphavirus RNA
      dependent RNA polymerase in the maintenance and repair of the poly(A) tail, an
      element required for replication of the viral genome.

PMID- 17005675
TI  - DNA vaccination can break immunological tolerance to PrP in wild-type mice and
      attenuates prion disease after intracerebral challenge.
AB  - Transmissible spongiform encephalopathies (TSEs) can be ameliorated by prion
      protein (PrP)-specific antibodies, but active immunization is complicated by
      immune tolerance to the normal cellular host protein (PrP(C)). Here, we show that
      DNA immunization of wild-type mice can break immune tolerance against the prion
      protein, resulting in the induction of PrP-specific antibody and T-cell
      responses. PrP immunogenicity was increased by fusion to the lysosomal targeting
      signal from LIMPII (lysosomal integral membrane protein type II). Although mice
      immunized with a PrP-LIMPII DNA vaccine showed a dramatic delay in the onset of
      early disease signs after intracerebral challenge, immunization against PrP also
      had some deleterious effects. These results clearly confirm the feasibility of
      using active immunization to protect against TSEs and, in the absence of
      effective treatments, indicate a suitable alternative for combating the spread of
      these diseases.

PMID- 17005676
TI  - Vaccinia virus infection attenuates innate immune responses and antigen
      presentation by epidermal dendritic cells.
AB  - Langerhans cells (LCs) are antigen-presenting cells in the skin that play
      sentinel roles in host immune defense by secreting proinflammatory molecules and
      activating T cells. Here we studied the interaction of vaccinia virus with XS52
      cells, a murine epidermis-derived dendritic cell line that serves as a surrogate
      model for LCs. We found that vaccinia virus productively infects XS52 cells, yet
      this infection displays an atypical response to anti-poxvirus agents. Whereas
      adenosine N1-oxide blocked virus production and viral protein synthesis during a
      synchronous infection, cytosine arabinoside had no effect at concentrations
      sufficient to prevent virus replication in BSC40 monkey kidney cells. Vaccinia
      virus infection of XS52 cells not only failed to elicit the production of various
      cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta
      (IL-1beta), IL-6, IL-10, IL-12 p40, alpha interferon (IFN-alpha), and IFN-gamma,
      it actively inhibited the production of proinflammatory cytokines TNF-alpha and
      IL-6 by XS52 cells in response to exogenous lipopolysaccharide (LPS) or
      poly(I:C). Infection with a vaccinia virus mutant lacking the E3L gene resulted
      in TNF-alpha secretion in the absence of applied stimuli. Infection of XS52 cells
      or BSC40 cells with the DeltaE3L virus, but not wild-type vaccinia virus,
      triggered proteolytic decay of IkappaBalpha. These results suggest a novel role
      for the E3L protein as an antagonist of the NF-kappaB signaling pathway. DeltaE3L
      infected XS52 cells secreted higher levels of TNF-alpha and IL-6 in response to
      LPS and poly(I:C) than did cells infected with the wild-type virus. XS52 cells
      were productively infected by a vaccinia virus mutant lacking the K1L gene.
      DeltaK1L-infected cells secreted higher levels of TNF-alpha and IL-6 in response
      to LPS than wild-type virus-infected cells. Vaccinia virus infection of primary
      LCs harvested from mouse epidermis was nonpermissive, although a viral reporter
      protein was expressed in the infected LCs. Vaccinia virus infection of primary
      LCs strongly inhibited their capacity for antigen-specific activation of T cells.
      Our results highlight suppression of the skin immune response as a feature of
      orthopoxvirus infection.

PMID- 17005677
TI  - Quantification of poly(I:C)-mediated protection against genital herpes simplex
      virus type 2 infection.
AB  - Alternative strategies for controlling the growing herpes simplex virus type 2
      (HSV-2) epidemic are needed. A novel class of immunomodulatory microbicides has
      shown promise as antiherpetics, including intravaginally applied CpG-containing
      oligodeoxynucleotides that stimulate toll-like receptor 9 (TLR9). In the current
      study, we quantified protection against experimental genital HSV-2 infection
      provided by an alternative nucleic acid-based TLR agonist, polyinosine-poly(C)
      (PIC) (TLR3 agonist). Using a protection quantification paradigm, groups of mice
      were PIC treated and then subdivided into groups challenged with escalating doses
      of HSV-2. Using this paradigm, a temporal window of PIC efficacy for single
      applications was defined as 1 day prior to (prophylactic) through 4 h after
      (therapeutic) viral challenge. PIC treatment within this window protected against
      10-fold-higher HSV-2 challenges, as indicated by increased 50% infectious dose
      values relative to those for vehicle-treated controls. Disease resolution and
      survival were significantly enhanced by repetitive PIC doses. Using optimal PIC
      regimens, cytokine induction was evaluated in murine vaginal lavages and in human
      vaginal epithelial cells. Similar induction patterns were observed, with kinetics
      that explained the limited durability of PIC-afforded protection. Daily PIC
      delivery courses did not generate sustained cytokine levels in murine vaginal
      fluids that would be indicative of local immunotoxicity. No evidence of
      immunotoxicity was observed in selected organs that were analyzed following
      repetitive vaginal PIC doses. Animal and in vitro data indicate that PIC may
      prove to be a valuable preventative microbicide and/or therapeutic agent against
      genital herpes by increasing resistance to HSV-2 and enhancing disease resolution
      following a failure of prevention.

PMID- 17005679
TI  - Human T-cell responses to vaccinia virus envelope proteins.
AB  - One approach for a safer smallpox vaccine is to utilize recombinant subunits
      rather than live vaccinia virus (VACV). The products of the VACV envelope genes
      A27L, L1R, B5R, and A33R induce protective antibodies in animal models. We
      propose that proteins that elicit T-cell responses, as well as neutralizing
      antibodies, will be important to include in a molecular vaccine. To evaluate VACV
      specific memory T-cell responses, peripheral blood mononuclear cells (PBMC) from
      four VACV vaccinees were tested against whole VACV and the individual envelope
      proteins A27, B5, L1, and A33, using gamma interferon enzyme-linked immunospot
      and cytokine flow cytometry assays. PBMC were stimulated with autologous
      dendritic cells infected with VACV or electroporated with individual VACV protein
      mRNAs. T-cell lines from all donors, vaccinated from 1 month to over 20 years
      ago, recognized all four VACV envelope proteins. Both CD4(+) and CD8(+) T-cell
      responses to each protein were detected. Further analysis focused on
      representative proteins B5 and A27. PBMC from a recent vaccinee exhibited high
      frequencies of CD4(+) and CD8(+) T-cell precursors to both B5 (19.8 and 20%,
      respectively) and A27 (6.8 and 3.7%). In comparison, B5- and A27-specific T-cell
      frequencies ranged from 0.4 to 1.3% in a donor vaccinated 3 years ago. Multiple
      CD4(+) and CD8(+) T-cell epitopes were identified from both A27 and B5, using
      overlapping 15-mer peptides. These data suggest that all four VACV envelope
      proteins may contribute to protective immunity, not only by inducing antibody
      responses, but also by eliciting T-cell responses.

PMID- 17005678
TI  - Autorepression of the human cytomegalovirus major immediate-early
      promoter/enhancer at late times of infection is mediated by the recruitment of
      chromatin remodeling enzymes by IE86.
AB  - The human cytomegalovirus major immediate-early protein IE86 is pivotal for
      coordinated regulation of viral gene expression throughout infection. A
      relatively promiscuous transactivator of viral early and late gene transcription,
      IE86 also acts during infection to negatively regulate its own promoter via
      direct binding to a 14-bp palindromic IE86-binding site, the cis repression
      sequence (crs), located between the major immediate-early promoter (MIEP) TATA
      box and the start of transcription. Although such autoregulation does not involve
      changes in the binding of basal transcription factors to the MIEP in vitro, it
      does appear to involve selective inhibition of RNA polymerase II recruitment.
      However, how this occurs is unclear. We show that autorepression by IE86 at late
      times of infection correlates with changes in chromatin structure around the MIEP
      during the course of infection and that this is likely to result from physical
      and functional interactions between IE86 and chromatin remodeling enzymes
      normally associated with transcriptional repression of cellular promoters.
      Firstly, we show that IE86-mediated autorepression is inhibited by histone
      deacetylase inhibitors. We also show that IE86 interacts, in vitro and in vivo,
      with the histone deacetylase HDAC1 and histone methyltransferases G9a and Suvar(3
      9)H1 and that coexpression of these chromatin remodeling enzymes with IE86
      increases autorepression of the MIEP. Finally, we show that mutation of the crs
      in the context of the virus abrogates the transcriptionally repressive chromatin
      phenotype normally found around the MIEP at late times of infection, suggesting
      that negative autoregulation by IE86 results, at least in part, from IE86
      mediated changes in chromatin structure of the viral MIEP.

PMID- 17005680
TI  - Characterization of a novel transferable CRM-1-independent nuclear export signal
      in a herpesvirus tegument protein that shuttles between the nucleus and
      cytoplasm.
AB  - A new group of nucleocytoplasmic shuttling proteins has recently been identified
      in the structural proteins encoded by several alphaherpesvirus UL47 genes.
      Nuclear import and export signals for the bovine herpesvirus type 1 UL47 protein
      (VP8 or bUL47) have been described previously. Here, we study the trafficking of
      bUL47 in detail and identify an import signal different from that shown before.
      It comprises a 20-residue N-terminal peptide that is fully transferable and
      targets a large, normally cytosolic protein to the nucleus. A conserved RRPRRS
      motif within this peptide was shown to be essential but not sufficient for
      nuclear targeting. Using interspecies heterokaryon assays, we further demonstrate
      that the export activity of the published leucine-rich nuclear export signal
      (NES) is also transferable to a large protein but is functionally weak compared
      to the activity of the HIV-1 Rev NES. We show that nuclear export dictated by
      this bUL47 NES is sensitive to leptomycin B (LMB) and therefore dependent on the
      export receptor CRM-1. However, nuclear export of full-length bUL47 is fully
      resistant to LMB, suggesting the presence of an additional NES. We go on to
      identify a second NES in bUL47 within a 28-residue peptide that is in close
      proximity to but entirely separable from the N-terminal import signal, and we use
      fluorescence loss in photobleaching to confirm its activity. This NES is
      resistant to leptomycin B, and therefore utilizes an export receptor other than
      CRM-1. As this new sequence bears little similarity to other export signals so
      far defined, we suggest it may be involved in bUL47 export from the nucleus via a
      novel cellular receptor.

PMID- 17005681
TI  - Coactivator-associated arginine methyltransferase 1 enhances transcriptional
      activity of the human T-cell lymphotropic virus type 1 long terminal repeat
      through direct interaction with Tax.
AB  - In this study, we demonstrate that the coactivator-associated arginine
      methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such
      as p300/CBP, is positively involved in the regulation of Tax transactivation.
      First, transfection studies demonstrated that overexpression of CARM1 wild-type
      protein resulted in increased Tax transactivation of the human T-cell
      lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast,
      transfection of a catalytically inactive CARM1 methyltransferase mutant did not
      enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB
      dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax
      and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding
      assays, in vivo coimmunoprecipitation, and confocal microscopy experiments.
      Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR
      promoter showed the association of CARM1 and methylated histone H3 with the
      template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription
      complex. Together, our data provide evidence that CARM1 enhances Tax
      transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and
      Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).

PMID- 17005682
TI  - trans regulation of cap-independent translation by a viral subgenomic RNA.
AB  - Many positive-strand RNA viruses generate 3'-coterminal subgenomic mRNAs to allow
      translation of 5'-distal open reading frames. It is unclear how viral genomic and
      subgenomic mRNAs compete with each other for the cellular translation machinery.
      Translation of the uncapped Barley yellow dwarf virus genomic RNA (gRNA) and
      subgenomic RNA1 (sgRNA1) is driven by the powerful cap-independent translation
      element (BTE) in their 3' untranslated regions (UTRs). The BTE forms a kissing
      stem-loop interaction with the 5' UTR to mediate translation initiation at the 5'
      end. Here, using reporter mRNAs that mimic gRNA and sgRNA1, we show that the
      abundant sgRNA2 inhibits translation of gRNA, but not sgRNA1, in vitro and in
      vivo. This trans inhibition requires the functional BTE in the 5' UTR of sgRNA2,
      but no translation of sgRNA2 itself is detectable. The efficiency of translation
      of the viral mRNAs in the presence of sgRNA2 is determined by proximity to the
      mRNA 5' end of the stem-loop that kisses the 3' BTE. Thus, the gRNA and sgRNA1
      have "tuned" their expression efficiencies via the site in the 5' UTR to which
      the 3' BTE base pairs. We conclude that sgRNA2 is a riboregulator that switches
      off translation of replication genes from gRNA while permitting translation of
      structural genes from sgRNA1. These results reveal (i) a new level of control of
      subgenomic-RNA gene expression, (ii) a new role for a viral subgenomic RNA, and
      (iii) a new mechanism for RNA-mediated regulation of translation.

PMID- 17005683
TI  - RNA silencing suppression by a second copy of the P1 serine protease of Cucumber
      vein yellowing ipomovirus, a member of the family Potyviridae that lacks the
      cysteine protease HCPro.
AB  - The P1 protein of viruses of the family Potyviridae is a serine proteinase, which
      is highly variable in length and sequence, and its role in the virus infection
      cycle is not clear. One of the proposed activities of P1 is to assist HCPro, the
      product that viruses of the genus Potyvirus use to counteract antiviral defense
      mediated by RNA silencing. Indeed, an HCPro-coding region is present in all the
      genomes of members of the genera Potyvirus, Rymovirus, and Tritimovirus that have
      been sequenced. However, it was recently reported that a sequence coding for
      HCPro is lacking in the genome of Cucumber vein yellowing virus (CVYV), a member
      of the genus Ipomovirus, the fourth monopartite genus of the family. In this
      study, we provide further evidence that P1 enhances the activity of HCPro in
      members of the genus Potyvirus and show that it is duplicated in the ipomovirus
      CVYV. The two CVYV P1 copies are arranged in tandem, and the second copy (P1b)
      has RNA silencing suppression activity. CVYV P1b suppressed RNA silencing induced
      either by sense green fluorescent protein (GFP) mRNA or by a GFP inverted repeat
      RNA, indicating that CVYV P1b acts downstream of the formation of double-stranded
      RNA. CVYV P1b also suppressed local silencing in agroinfiltrated patches of
      transgenic Nicotiana benthamiana line 16c and delayed its propagation to the
      neighboring cells. However, neither the short-distance nor long-distance systemic
      spread of silencing of the GFP transgene was completely blocked by CVYV P1b. CVYV
      P1b and P1-HCPro from the potyvirus Plum pox virus showed very similar behaviors
      in all the assays carried out, suggesting that evolution has found a way to
      counteract RNA silencing by similar mechanisms using very different proteins in
      viruses of the same family.

PMID- 17005684
TI  - Phosphorylation of MCM4 at sites inactivating DNA helicase activity of the MCM4
      MCM6-MCM7 complex during Epstein-Barr virus productive replication.
AB  - Induction of Epstein-Barr virus (EBV) lytic replication blocks chromosomal DNA
      replication notwithstanding an S-phase-like cellular environment with high cyclin
      dependent kinase (CDK) activity. We report here that the phosphorylated form of
      MCM4, a subunit of the MCM complex essential for chromosomal DNA replication,
      increases with progression of lytic replication, Thr-19 and Thr-110 being
      CDK2/CDK1 targets whose phosphorylation inactivates MCM4-MCM6-MCM7 (MCM4-6-7)
      complex-associated DNA helicase. Expression of EBV-encoded protein kinase (EBV
      PK) in HeLa cells caused phosphorylation of these sites on MCM4, leading to cell
      growth arrest. In vitro, the sites of MCM4 of the MCM4-6-7 hexamer were confirmed
      to be phosphorylated with EBV-PK, with the same loss of helicase activity as with
      CDK2/cyclin A. Introducing mutations in the N-terminal six Ser and Thr residues
      of MCM4 reduced the inhibition by CDK2/cyclin A, while EBV-PK inhibited the
      helicase activities of both wild-type and mutant MCM4-6-7 hexamers, probably
      since EBV-PK can phosphorylate MCM6 and another site(s) of MCM4 in addition to
      the N-terminal residues. Therefore, phosphorylation of the MCM complex by
      redundant actions of CDK and EBV-PK during lytic replication might provide one
      mechanism to block chromosomal DNA replication in the infected cells through
      inactivation of DNA unwinding by the MCM4-6-7 complex.

PMID- 17005685
TI  - Asynchronous progression through the lytic cascade and variations in
      intracellular viral loads revealed by high-throughput single-cell analysis of
      Kaposi's sarcoma-associated herpesvirus infection.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus-8) is
      frequently tumorigenic in immunocompromised patients. The average intracellular
      viral copy number within infected cells, however, varies markedly by tumor type.
      Since the KSHV-encoded latency-associated nuclear antigen (LANA) tethers viral
      episomes to host heterochromatin and displays a punctate pattern by fluorescence
      microscopy, we investigated whether accurate quantification of individual LANA
      dots is predictive of intracellular viral genome load. Using a novel technology
      that integrates single-cell imaging with flow cytometry, we found that both the
      number and the summed immunofluorescence of individual LANA dots are directly
      proportional to the amount of intracellular viral DNA. Moreover, combining viral
      (immediate early lytic replication and transcription activator [RTA] and late
      lytic K8.1) and cellular (syndecan-1) staining with image-based flow cytometry,
      we were also able to rapidly and simultaneously distinguish among cells
      supporting latent, immediate early lytic, early lytic, late lytic, and a
      potential fourth "delayed late" category of lytic replication. Applying image
      based flow cytometry to KSHV culture models, we found that de novo infection
      results in highly varied levels of intracellular viral load and that lytic
      induction of latently infected cells likewise leads to a heterogeneous population
      at various stages of reactivation. These findings additionally underscore the
      potential advantages of studying KSHV biology with high-throughput analysis of
      individual cells.

PMID- 17005686
TI  - Suppression of proinflammatory signal transduction and gene expression by the
      dual nucleic acid binding domains of the vaccinia virus E3L proteins.
AB  - Cells have evolved elaborate mechanisms to counteract the onslaught of viral
      infections. To activate these defenses, the viral threat must be recognized.
      Danger signals, or pathogen-associated molecular patterns, that are induced by
      pathogens include double-stranded RNA (dsRNA), viral single-stranded RNA,
      glycolipids, and CpG DNA. Understanding the signal transduction pathways
      activated and host gene expression induced by these danger signals is vital to
      understanding virus-host interactions. The vaccinia virus E3L protein is involved
      in blocking the host antiviral response and increasing pathogenesis, functions
      that map to separate C-terminal dsRNA- and N-terminal Z-DNA-binding domains.
      Viruses containing mutations in these domains allow modeling of the role of dsRNA
      and Z-form nucleic acid in the host response to virus infection. Deletions in the
      Z-DNA- or dsRNA-binding domains led to activation of signal transduction cascades
      and up-regulation of host gene expression, with many genes involved in the
      inflammatory response. These data suggest that poxviruses actively inhibit
      cellular recognition of viral danger signals and the subsequent cellular response
      to the viral threat.

PMID- 17005687
TI  - Packaging of brome mosaic virus subgenomic RNA is functionally coupled to
      replication-dependent transcription and translation of coat protein.
AB  - In Brome mosaic virus (BMV), genomic RNA1 (gB1) and RNA2 (gB2), encoding the
      replication factors, are packaged into two separate virions, whereas genomic RNA3
      (gB3) and its subgenomic coat protein (CP) mRNA (sgB4) are copackaged into a
      third virion. In vitro assembly assays performed between a series of deletion
      variants of sgB4 and wild-type (wt) CP subunits demonstrated that packaging of
      sgB4 is independent of sequences encoding the CP open reading frame. To confirm
      these observations in vivo and to unravel the mechanism of sgB4 copackaging, an
      Agrobacterium-mediated transient in vivo expression system (P. Annamalai and A.
      L. N. Rao, Virology 338:96-111, 2005) that effectively uncouples replication from
      packaging was used. Cultures of agrotransformants, engineered to express sgB4 and
      CP subunits either transiently (sgB4(Trans) and CP(Trans)) or in replication
      dependent transcription and translation when complemented with gB1 and gB2
      (sgB4(Rep) and CP(Rep)), were mixed in all four pair-wise combinations and
      infiltrated to Nicotiana benthamiana leaves to systematically evaluate
      requirements regulating sgB4 packaging. The data revealed that (i) in the absence
      of replication, packaging was nonspecific, since transiently expressed CP
      subunits efficiently packaged ubiquitous cellular RNA as well as transiently
      expressed sgB4 and its deletion variants; (ii) induction of viral replication
      increased specificity of RNA packaging; and most importantly, (iii) efficient
      packaging of sgB4, reminiscent of the wt scenario, is functionally coupled not
      only to its transcription via replication but also to translation of CP from
      replication-derived mRNA, a mechanism that appears to be conserved among positive
      strand RNA viruses of plants (this study), animals (flock house virus), and
      humans (poliovirus).

PMID- 17005689
TI  - The amino terminus of the herpes simplex virus 1 protein Vhs mediates membrane
      association and tegument incorporation.
AB  - Assembly of herpes simplex viruses (HSV) is a poorly understood process involving
      multiple redundant interactions between large number of tegument and envelope
      proteins. We have previously shown (G. E. Lee, G. A. Church, and D. W. Wilson, J.
      Virol. 77:2038-2045, 2003) that the virion host shutoff (Vhs) tegument protein is
      largely insoluble in HSV-infected cells and is also stably associated with
      membranes. Here we demonstrate that both insolubility and stable membrane binding
      are stimulated during the course of an HSV infection. Furthermore, we have found
      that the amino-terminal 42 residues of Vhs are sufficient to mediate membrane
      association and tegument incorporation when fused to a green fluorescent protein
      (GFP) reporter. Particle incorporation correlates with sorting to cytoplasmic
      punctate structures that may correspond to sites of HSV assembly. We conclude
      that the amino terminus of Vhs mediates targeting to sites of HSV assembly and to
      the viral tegument.

PMID- 17005688
TI  - Tyro3 family-mediated cell entry of Ebola and Marburg viruses.
AB  - Filoviruses, represented by the genera Ebolavirus and Marburgvirus, cause a
      lethal hemorrhagic fever in humans and in nonhuman primates. Although filovirus
      can replicate in various tissues or cell types in these animals, the molecular
      mechanisms of its broad tropism remain poorly understood. Here we show the
      involvement of members of the Tyro3 receptor tyrosine kinase family-Axl, Dtk, and
      Mer-in cell entry of filoviruses. Ectopic expression of these family members in
      lymphoid cells, which otherwise are highly resistant to filovirus infection,
      enhanced infection by pseudotype viruses carrying filovirus glycoproteins on
      their envelopes. This enhancement was reduced by antibodies to Tyro3 family
      members, Gas6 ligand, or soluble ectodomains of the members. Live Ebola viruses
      infected both Axl- and Dtk-expressing cells more efficiently than control cells.
      Antibody to Axl inhibited infection of pseudotype viruses in a number of Axl
      positive cell lines. These results implicate each Tyro3 family member as a cell
      entry factor in filovirus infection.

PMID- 17005690
TI  - Differential enhancement of dengue virus immune complex infectivity mediated by
      signaling-competent and signaling-incompetent human Fcgamma RIA (CD64) or
      FcgammaRIIA (CD32).
AB  - Fcgamma receptor (FcgammaR)-mediated entry of infectious dengue virus immune
      complexes into monocytes/macrophages is hypothesized to be a key event in the
      pathogenesis of complicated dengue fever. FcgammaRIA (CD64) and FcgammaRIIA
      (CD32), which predominate on the surface of such dengue virus-permissive cells,
      were compared for their influence on the infectivity of dengue 2 virus immune
      complexes formed with human dengue virus antibodies. A signaling immunoreceptor
      tyrosine-based activation motif (ITAM) incorporated into the accessory gamma
      chain subunit that associates with FcgammaRIA and constitutively in FcgammaRIIA
      is required for phagocytosis mediated by these receptors. To determine whether
      FcgammaRIA and FcgammaRIIA activation functions are also required for
      internalization of infectious dengue virus immune complexes, we generated native
      and signaling-incompetent versions of each receptor by site-directed mutagenesis
      of ITAM tyrosine residues. Plasmids designed to express these receptors were
      transfected into COS-7 cells, and dengue virus replication was measured by plaque
      assay and flow cytometry. We found that both receptors mediated enhanced dengue
      virus immune complex infectivity but that FcgammaRIIA appeared to do so far more
      effectively. Abrogation of FcgammaRIA signaling competency, either by expression
      without gamma-chain or by coexpression with gamma-chain mutants, was associated
      with significant impairment of phagocytosis and of dengue virus immune complex
      infectivity. Abrogation of FcgammaRIIA signaling competency was also associated
      with equally impaired phagocytosis but had no discernible effect on dengue virus
      immune complex infectivity. These findings point to fundamental differences
      between FcgammaRIA and FcgammaRIIA with respect to their immune-enhancing
      capabilities and suggest that different mechanisms of dengue virus immune complex
      internalization may operate between these FcgammaRs.

PMID- 17005691
TI  - EBNA-3B- and EBNA-3C-regulated cellular genes in Epstein-Barr virus-immortalized
      lymphoblastoid cell lines.
AB  - The cellular pathways that Epstein-Barr virus (EBV) manipulates in order to
      effect its lifelong persistence within hosts and facilitate its transmission
      between hosts are not well understood. The EBV nuclear antigen 3 (EBNA-3) family
      of latent infection proteins consists of transcriptional regulators that
      influence viral and cellular gene expression in EBV-infected cells. To identify
      EBNA-3B- and EBNA-3C-regulated cellular genes potentially important for virus
      infection in vivo, we studied a lymphoblastoid cell line (LCL) infected with an
      unusual EBV mutant, where a genetic manipulation to delete EBNA-3B also resulted
      in a significant decrease in EBNA-3C expression and slower than normal growth
      (3B(-)/3C(low)). Transcriptional profiling was performed on the 3B(-)/3C(low)
      LCLs, and comparison of mutant and wild-type LCL profiles resulted in a group of
      21 probe sets representing 16 individual genes showing statistically significant
      differences in expression. Further quantitative reverse transcription-PCR
      analyses comparing 3B(-)/3C(low) LCLs to a previously described EBNA-3B mutant
      (3B(-)) where EBNA-3C expression was normal revealed three potential EBNA-3B
      repressed genes, three potential EBNA-3C-repressed genes, and two potential EBNA
      3C-activated genes. The most highly EBNA-3C-repressed gene was Jagged1, a cell
      surface ligand and inducer of the Notch receptor signaling pathway that is
      usurped by EBV genes essential for B-cell immortalization. 3B(-)/3C(low) LCLs
      expressed increased levels of Jagged1 protein and were able to more efficiently
      induce functional Notch signaling, and this signaling was dependent on Notch
      cleavage by gamma-secretase. However, inhibiting gamma-secretase-mediated Notch
      cleavage did not rescue 3B(-)/3C(low) LCL growth, suggesting that EBNA-3C
      mediated repression of this signaling pathway did not contribute to LCL growth in
      tissue culture. Similarly, expression of the chemokine receptor CXCR4 was
      reproducibly upregulated in EBNA-3B-null LCLs. Since deletion of EBNA-3B has no
      significant impact on B-cell immortalization in tissue culture, this finding
      suggested that EBNA-3B-mediated regulation of CXCR4 may be an important viral
      strategy for alteration of B-cell homing in the infected host. These studies
      identify two cellular genes that do not contribute to EBV-induced B-cell growth
      but whose expression levels are strongly EBNA-3 regulated in EBV-infected primary
      B cells. These EBV-manipulated cellular pathways may be important for virus
      survival or transmission in humans, and their independence from EBV-induced B
      cell growth makes them potential targets for testing in vivo with the rhesus
      lymphocryptovirus animal model for EBV infection.

PMID- 17005692
TI  - CD127+CCR5+CD38+++ CD4+ Th1 effector cells are an early component of the primary
      immune response to vaccinia virus and precede development of interleukin-2+
      memory CD4+ T cells.
AB  - The stages of development of human antigen-specific CD4+ T cells responding to
      viral infection and their differentiation into long-term memory cells are not
      well understood. The inoculation of healthy adults with vaccinia virus presents
      an opportunity to study these events intensively. Between days 11 and 14
      postinoculation, there was a peak of proliferating CCR5+CD38+++ CD4+ effector
      cells which contained the cytotoxic granule marker T-cell intracellular antigen 1
      and included gamma interferon (IFN-gamma)-producing vaccinia virus-specific CD4+
      T cells. The majority of these initial vaccinia virus-specific CD4+ T cells were
      CD127+ and produced interleukin-2 (IL-2) but not CTLA-4 in response to
      restimulation in vitro. Between days 14 and 21, there was a switch from IFN-gamma
      and IL-2 coexpression to IL-2 production only, coinciding with a resting
      phenotype and an increased in vitro proliferation response. The early
      CCR5+CD38+++ vaccinia virus-specific CD4+ T cells were similar to our previous
      observations of human immunodeficiency virus (HIV)-specific CD4+ T cells in
      primary HIV type 1 (HIV-1) infection, but the vaccinia virus-specific cells
      expressed much more CD127 and IL-2 than we previously found in their HIV-specific
      counterparts. The current study provides important information on the
      differentiation of IL-2+ vaccinia virus-specific memory cells, allowing further
      study of antiviral effector CD4+ T cells in healthy adults and their dysfunction
      in HIV-1 infection.

PMID- 17005694
TI  - Double-stranded RNA binding by a heterodimeric complex of murine cytomegalovirus
      m142 and m143 proteins.
AB  - In response to viral infection, cells activate a variety of antiviral responses,
      including several that are triggered by double-stranded (ds) RNA. Among these are
      the protein kinase R and oligoadenylate synthetase/RNase L pathways, both of
      which result in the shutoff of protein synthesis. Many viruses, including human
      cytomegalovirus, encode dsRNA-binding proteins that prevent the activation of
      these pathways and thereby enable continued protein synthesis and viral
      replication. We have extended these analyses to another member of the beta
      subfamily of herpesviruses, murine cytomegalovirus (MCMV), and now report that
      products of the m142 and m143 genes together bind dsRNA. Coimmunoprecipitation
      experiments demonstrate that these two proteins interact in infected cells,
      consistent with their previously reported colocalization. Jointly, but not
      individually, the proteins rescue replication of a vaccinia virus mutant with a
      deletion of the dsRNA-binding protein gene E3L (VVDeltaE3L). Like the human
      cytomegalovirus dsRNA-binding protein genes TRS1 and IRS1, m142 and m143 are
      members of the US22 gene family. We also found that two other members of the MCMV
      US22 family, M23 and M24, encode dsRNA-binding proteins, but they do not rescue
      VVDeltaE3L replication. These results reveal that MCMV, like many other viruses,
      encodes dsRNA-binding proteins, at least two of which can inhibit dsRNA-activated
      antiviral pathways. However, unlike other well-studied examples, the MCMV
      proteins appear to act in a heterodimeric complex.

PMID- 17005693
TI  - Infection of CD127+ (interleukin-7 receptor+) CD4+ cells and overexpression of
      CTLA-4 are linked to loss of antigen-specific CD4 T cells during primary human
      immunodeficiency virus type 1 infection.
AB  - We recently found that human immunodeficiency virus (HIV)-specific CD4+ T cells
      express coreceptor CCR5 and activation antigen CD38 during early primary HIV-1
      infection (PHI) but then rapidly disappear from the circulation. This cell loss
      may be due to susceptibility to infection with HIV-1 but could also be due to
      inappropriate apoptosis, an expansion of T regulatory cells, trafficking out of
      the circulation, or dysfunction. We purified CD38+++CD4+ T cells from peripheral
      blood mononuclear cells, measured their level of HIV-1 DNA by PCR, and found that
      about 10% of this population was infected. However, a small subset of HIV
      specific CD4+) T cells also expressed CD127, a marker of long-term memory cells.
      Purified CD127+CD4+ lymphocytes contained fivefold more copies of HIV-1 DNA per
      cell than did CD127-negative CD4+ cells, suggesting preferential infection of
      long-term memory cells. We observed no apoptosis of antigen-specific CD4+ T cells
      in vitro and only a small increase in CD45RO+CD25+CD127dimCD4+ T regulatory cells
      during PHI. However, 40% of CCR5+CD38+++ CD4+ T cells expressed gut-homing
      integrins, suggesting trafficking through gut-associated lymphoid tissue (GALT).
      Furthermore, 80% of HIV-specific CD4+ T cells expressed high levels of the
      negative regulator CTLA-4 in response to antigen stimulation in vitro, which was
      probably contributing to their inability to produce interleukin-2 and
      proliferate. Taken together, the loss of HIV-specific CD4+ T cells is associated
      with a combination of an infection of CCR5+ CD127+ memory CD4+ T cells, possibly
      in GALT, and a high expression of the inhibitory receptor CTLA-4.

PMID- 17005695
TI  - Murine cytomegalovirus m142 and m143 are both required to block protein kinase R
      mediated shutdown of protein synthesis.
AB  - Cytomegaloviruses carry the US22 family of genes, which have common sequence
      motifs but diverse functions. Only two of the 12 US22 family genes of murine
      cytomegalovirus (MCMV) are essential for virus replication, but their functions
      have remained unknown. In the present study, we deleted the essential US22 family
      genes, m142 and m143, from the MCMV genome and propagated the mutant viruses on
      complementing cells. The m142 and the m143 deletion mutants were both unable to
      replicate in noncomplementing cells at low and high multiplicities of infection.
      In cells infected with the deletion mutants, viral immediate-early and early
      proteins were expressed, but viral DNA replication and synthesis of the late-gene
      product glycoprotein B were inhibited, even though mRNAs of late genes were
      present. Global protein synthesis was impaired in these cells, which correlated
      with phosphorylation of the double-stranded RNA-dependent protein kinase R (PKR)
      and its target protein, the eukaryotic translation initiation factor 2alpha,
      suggesting that m142 and m143 are necessary to block the PKR-mediated shutdown of
      protein synthesis. Replication of the m142 and m143 knockout mutants was
      partially restored by expression of the human cytomegalovirus TRS1 gene, a known
      double-stranded-RNA-binding protein that inhibits PKR activation. These results
      indicate that m142 and m143 are both required for inhibition of the PKR-mediated
      host antiviral response.

PMID- 17005696
TI  - Efficient mother-to-child transfer of antiretroviral immunity in the context of
      preclinical monoclonal antibody-based immunotherapy.
AB  - When mice under the age of 5 to 6 days are infected, the FrCas(E) retrovirus
      induces a neurodegenerative disease leading to death within 1 to 2 months. We
      have recently reported that transient treatment with a neutralizing monoclonal
      antibody (MAb) shortly after infection, in addition to an expected immediate
      decrease in the viral load, also favors the development of a strong protective
      immune response that persists long after the MAb has been cleared. This
      observation may have important therapeutic consequences, as it suggests that MAbs
      might be used, not only as direct neutralizing agents, but also as
      immunomodulatory agents enabling patients to mount their own antiviral immune
      responses. We have investigated whether immunoglobulins from mothers who
      displayed a strong anti-FrCas(E) humoral response induced upon MAb treatment
      could affect both viremia and the immune systems of FrCas(E)-infected pups till
      adult age upon placental and/or breastfeeding transfer. The strongest effects,
      i.e., reduction in the viral load and induction of protective humoral antiviral
      responses, were observed upon breastfeeding alone and breastfeeding plus
      placental immunity transfer. However, placental transfer of anti-FrCas(E)
      antibodies was sufficient to both protect neonatally infected animals and help
      them initiate a neutralizing anti-FrCas(E) response. Also, administration of a
      neutralizing MAb to naive mothers during late gestation and breastfeeding could
      generate similar effects. Taken together, our data support the concept that
      passive immunotherapies during late gestation and/or breastfeeding might help
      retrovirally infected neonates prime their own protective immune responses, in
      addition to exerting an immediate antiviral effect.

PMID- 17005697
TI  - Induction of a protective immune response against viral nervous necrosis in the
      European sea bass Dicentrarchus labrax by using betanodavirus virus-like
      particles.
AB  - Betanodaviruses are causative agents of viral nervous necrosis (VNN), a
      devastating disease of cultured marine fish worldwide. Virus particles contain a
      single type of coat protein that spontaneously assembles into virus-like
      particles (VLPs) when expressed in a baculovirus expression system. In the
      present study, the immunogenicity of betanodavirus VLPs and the protection they
      confer against VNN in the European sea bass Dicentrarchus labrax were
      investigated. Enzyme-linked immunosorbent assay and seroneutralization tests
      performed on plasma from fish vaccinated intramuscularly with doses as low as 0.1
      microg of VLPs indicated that the VLPs elicited the synthesis of specific
      antibetanodavirus antibodies with neutralizing activity. Moreover, fish
      vaccinated with VLPs were protected from challenge with live virus. Both the
      immune response and the protective effect against viral challenge were dose
      dependent. Reverse transcription-PCR data indicated that higher doses of vaccine
      also reduced the number of fish containing detectable quantities of betanodavirus
      RNA on day 30 after challenge. Taken together these data strongly support the
      hypothesis that VLPs obtained in the baculovirus expression system may represent
      an effective vaccine against VNN.

PMID- 17005698
TI  - Murine model for dengue virus-induced lethal disease with increased vascular
      permeability.
AB  - Lack of an appropriate animal model for dengue virus (DEN), which causes dengue
      fever and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), has impeded
      characterization of the mechanisms underlying the disease pathogenesis. The
      cardinal feature of DHF/DSS, the severe form of DEN infection, is increased
      vascular permeability. To develop a murine model that is more relevant to
      DHF/DSS, a novel DEN strain, D2S10, was generated by alternately passaging a non
      mouse-adapted DEN strain between mosquito cells and mice, thereby mimicking the
      natural transmission cycle of the virus between mosquitoes and humans. After
      infection with D2S10, mice lacking interferon receptors died early without
      manifesting signs of paralysis, carried infectious virus in both non-neuronal and
      neuronal tissues, and exhibited signs of increased vascular permeability. In
      contrast, mice infected with the parental DEN strain developed paralysis at late
      times after infection, contained detectable levels of virus only in the central
      nervous system, and displayed normal vascular permeability. In the mice infected
      with D2S10, but not the parental DEN strain, significant levels of serum tumor
      necrosis factor alpha (TNF-alpha) were produced, and the neutralization of TNF
      alpha activity prevented early death of D2S10-infected mice. Sequence analysis
      comparing D2S10 to its parental strain implicated a conserved region of amino
      acid residues in the envelope protein as a possible source for the D2S10
      phenotype. These results demonstrate that D2S10 causes a more relevant disease in
      mice and that TNF-alpha may be one of several key mediators of severe DEN-induced
      disease in mice. This report represents a significant advance in animal models
      for severe DEN disease, and it begins to provide mechanistic insights into DEN
      induced disease in vivo.

PMID- 17005699
TI  - Functional interaction between human herpesvirus 6 immediate-early 2 protein and
      ubiquitin-conjugating enzyme 9 in the absence of sumoylation.
AB  - The immediate-early 2 (IE2) protein of human herpesvirus 6 is a potent
      transactivator of cellular and viral promoters. To better understand the biology
      of IE2, we generated a LexA-IE2 fusion protein and screened, using the yeast two
      hybrid system, a Jurkat T-cell cDNA library for proteins that could interact with
      IE2. The most frequently isolated IE2-interacting protein was the human ubiquitin
      conjugating enzyme 9 (Ubc9), a protein involved in the small ubiquitin-like
      modifier (SUMO) conjugation pathway. Using deletion mutants of IE2, we mapped the
      IE2-Ubc9-interacting region to residues 989 to 1037 of IE2. The interaction was
      found to be of functional significance to IE2, as Ubc9 overexpression
      significantly repressed promoter activation by IE2. The C93S Ubc9 mutant
      exhibited a similar effect on IE2, indicating that the E2 SUMO-conjugating
      function of Ubc9 is not required for its repressive action on IE2. No consensus
      sumoylation sites or evidence of IE2 conjugation to SUMO could be demonstrated
      under in vivo or in vitro conditions. Moreover, expression levels and nuclear
      localization of IE2 were not altered by Ubc9 overexpression, suggesting that
      Ubc9's repressive function likely occurs at the transcriptional complex level.
      Overall, our results indicate that Ubc9 influences IE2's function and provide new
      information on the complex interactions that occur between herpesviruses and the
      sumoylation pathway.

PMID- 17005700
TI  - Naive T-cell depletion related to infection by X4 human immunodeficiency virus
      type 1 in poor immunological responders to highly active antiretroviral therapy.
AB  - The reasons for poor CD4+ T-cell recovery in some human immunodeficiency virus
      (HIV)-infected subjects despite effective highly active antiretroviral therapy
      (HAART) remain unclear. We recently reported that CXCR4-using (X4) HIV-1 could be
      gradually selected in cellular reservoirs during sustained HAART. Because of the
      differential expression of HIV-1 coreceptors CCR5 and CXCR4 on distinct T-cell
      subsets, the residual replication of R5 and X4 viruses could have different
      impacts on T-cell homeostasis during immune reconstitution on HAART. We examined
      this hypothesis and the mechanisms of CD4+ T-cell restoration by comparing the
      virological and immunological features of 15 poor and 15 good immunological
      responders to HAART. We found a high frequency of X4 viruses in the poor
      immunological responders. But the levels of intrathymic proliferation of the two
      groups were similar regardless of whether they were infected by R5 or X4 virus.
      The frequency of recent thymic emigrants in the poor immunological responders was
      also similar to that found in the good immunological responders, despite their
      reduced numbers of naive CD4+ T cells. Our data, rather, suggest that the naive T
      cell compartment is drained by a high rate of mature naive cell loss in the
      periphery due to bystander apoptosis or activation-induced differentiation. X4
      viruses could play a role in the depletion of naive T cells in poor immunological
      responders to HAART by triggering persistent T-cell activation and bystander
      apoptosis via gp120-CXCR4 interactions.

PMID- 17005702
TI  - Differential signaling networks induced by mild and lethal hemorrhagic fever
      virus infections.
AB  - The family Arenaviridae includes several National Institutes of Allergy and
      Infections Diseases category A select agents which cause hemorrhagic fever. There
      are few vaccines available, and treatment is limited to ribavirin, which varies
      in efficacy. Development of new antiviral compounds has been hindered by a lack
      of understanding of the molecular basis of pathogenesis. We used two variants of
      Pichinde virus, one attenuated and one virulent in the guinea pig model, to
      delineate the host determinants which lead to either viral clearance or lethal
      disease. By analyzing protein level changes using pathway analysis, we have
      identified key intermediates which may be targets for therapeutic intervention.

PMID- 17005701
TI  - Neutralized adenovirus-immune complexes can mediate effective gene transfer via
      an Fc receptor-dependent infection pathway.
AB  - Neutralization of adenovirus (Ad) by anti-Ad neutralizing antibodies in serum
      involves formation of Ad-immune complexes that prevent the virus from interacting
      with target cells. We hypothesized that Ad-immune complexes likely contain viable
      Ad vectors which, although no longer capable of gaining access to receptors on
      target cells, may be able to express transgenes in cells bearing Fc receptors for
      immunoglobulins, i.e., that antibody-based "neutralization" of Ad vectors may be
      circumvented by the Fc receptor pathway. To test this hypothesis, we expressed
      the Fcgamma receptor IIA (FcgammaR) in A549 lung epithelial cells or human dermal
      fibroblasts and evaluated gene transfer in the presence of human neutralizing
      anti-Ad serum. FcgammaR-expressing cells bound and internalized copious amounts
      of Ad, with a distinct population of internalized Ad trafficking to the nucleus.
      The dose-response curves for inhibition of gene transfer revealed that FcgammaR
      expressing cells required a more-than-10-fold higher concentration of anti-Ad
      serum to achieve 50% inhibition of Ad-encoded beta-galactosidase expression
      compared with non-FcgammaR-expressing cells. The discrepancy between
      neutralization of Ad during infection of FcgammaR-expressing cells and
      neutralization of Ad during infection of non-FcgammaR-expressing cells occurred
      with either heat-inactivated or non-heat-inactivated sera, was blocked by
      addition of purified Fc domain protein, and did not require the cytoplasmic
      domain of FcgammaR, suggesting that immune complex internalization proceeded via
      endocytosis rather than phagocytosis. FcgammaR-mediated infection by Ad-immune
      complexes did not require expression of the coxsackie virus-Ad receptor (CAR)
      since similar data were obtained when CAR-deficient human dermal fibroblasts were
      engineered to express FcgammaR. However, interaction of the Ad penton base with
      cell surface integrins contributed to the difference in neutralization between
      FcgammaR-expressing and non-FcgammaR-expressing cells. The data indicate that
      complexes formed from Ad and anti-Ad neutralizing antibodies, while compromised
      with respect to infection of non-FcgammaR-expressing target cells, maintain the
      potential to transfer genes to FcgammaR-expressing cells, with consequent
      expression of the transgene. The formation of Ad-immune complexes that can target
      viable virus to antigen-presenting cells may account for the success of Ad-based
      vaccines administered in the presence of low levels of neutralizing anti-Ad
      antibody.

PMID- 17005703
TI  - Production of infectious hepatitis C virus by well-differentiated, growth
      arrested human hepatoma-derived cells.
AB  - Dimethyl sulfoxide (DMSO) has been shown to induce the differentiation of primary
      hepatocytes in vitro. When actively dividing poorly differentiated human hepatoma
      derived (Huh7) cells were cultured in the presence of 1% DMSO, cells became
      cytologically differentiated and transitioned into a nondividing state,
      characterized by the induction of hepatocyte-specific genes. Moreover, these
      cells were highly permissive for acute hepatitis C virus (HCV) infection, and
      persistent long term infection of these cultures could also be achieved. As HCV
      naturally replicates in highly differentiated nondividing human hepatocytes, this
      system may more accurately mimic the conditions under which HCV replicates in
      vivo than previous models using poorly differentiated rapidly dividing hepatoma
      cells.

PMID- 17005704
TI  - Isolation and characterization of an infectious replication-competent molecular
      clone of ecotropic porcine endogenous retrovirus class C.
AB  - Xenotransplantation of pig organs is complicated by the existence of polytropic
      replication-competent porcine endogenous retroviruses (PERV) capable of infecting
      human cells. The potential for recombination between ecotropic PERV-C and human
      tropic PERV-A and PERV-B adds another level of infectious risk. Proviral PERV-C
      were characterized in MAX-T cells derived from d/d haplotype miniature swine.
      Three proviruses were cloned from a genomic library. Clone PERV-C(1312) generated
      infectious particles after transfection into porcine ST-IOWA cells. Electron
      microscopy revealed the same morphologies of virions in MAX-T cells and in ST
      IOWA cells infected with cell-free PERV-C(1312) particles, indicating that MAX-T
      cells harbor one functional PERV-C provirus.

PMID- 17005705
TI  - Nuclear import defect of human immunodeficiency virus type 1 DNA flap mutants is
      not dependent on the viral strain or target cell type.
AB  - We have previously established, using human immunodeficiency virus type 1 (HIV-1)
      strain LAI, that the HIV-1 central DNA Flap acts as a cis determinant of viral
      genome nuclear import. Although the impact of the DNA Flap on nuclear import has
      already found numerous independent confirmations in the context of lentivirus
      vectors, it has been claimed that it may be nonessential for infectious virus
      strains LAI, YU-2 (J. D. Dvorin et al., J. Virol. 76:12087-12096, 2002), HXB2,
      and NL4-3 (A. Limon et al., J. Virol. 76:12078-12086, 2002). We conducted a
      detailed analysis of virus infectivity using the provirus clones provided by the
      authors and analogous target cells. In contrast to published data, our results
      show that all cPPT mutant viruses exhibit reduced infectivity corresponding to a
      nuclear import defect irrespective of the viral genetic background or target
      cell.

PMID- 17005706
TI  - Rabies virus infection of primary neuronal cultures and adult mice: failure to
      demonstrate evidence of excitotoxicity.
AB  - Cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse
      fetuses infected with the CVS strain of rabies virus showed loss of trypan blue
      exclusion, morphological apoptotic features, and activated caspase 3 expression,
      indicating apoptosis. The NMDA (N-methyl-D-aspartate acid) antagonists ketamine
      (125 microM) and MK-801 (60 microM) were found to have no significant
      neuroprotective effect on CVS-infected neurons, while the caspase inhibitor Ac
      Asp-Glu-Val aspartic acid aldehyde (25 microM) exerted a marked neuroprotective
      effect. Glutamate-stimulated increases in levels of intracellular calcium were
      reduced in CVS-infected hippocampal neurons. Ketamine (120 mg/kg of body
      weight/day intraperitoneally) given to CVS-infected adult mice produced no
      beneficial effects. We have found no supportive evidence that excitotoxicity
      plays an important role in rabies virus infection.

PMID- 17005707
TI  - Human cytomegalovirus UL84 protein contains two nuclear export signals and
      shuttles between the nucleus and the cytoplasm.
AB  - Previous studies defined pUL84 of human cytomegalovirus as an essential
      regulatory protein with nuclear localization that was proposed to act during
      initiation of viral-DNA synthesis. Recently, we demonstrated that a complex
      domain of 282 amino acids within pUL84 functions as a nonconventional nuclear
      localization signal. Sequence inspection of this domain revealed the presence of
      motifs with homology to leucine-rich nuclear export signals. Here, we report the
      identification of two functional, autonomous nuclear export signals and show that
      pUL84 acts as a CRM-1-dependent nucleocytoplasmic shuttling protein. This
      suggests an unexpected cytoplasmic role for this essential viral regulatory
      protein.

PMID- 17005708
TI  - Alternate polypurine tracts affect rous sarcoma virus integration in vivo.
AB  - When the endogenous polypurine tract (PPT) of the Rous sarcoma virus (RSV)
      derived vector RSVP(A)Z was replaced with alternate retroviral PPTs, the fraction
      of unintegrated viral DNA with the normal consensus ends significantly decreased
      and the retention of part of the PPT significantly increased. If the terminus of
      the U3 long terminal repeat (LTR) is aberrant, RSV integrase can correctly
      process and integrate the normal U5 LTR into the host genome. However, the
      canonical CA is not involved in joining the aberrant U3 LTR to the host DNA,
      generating either large duplications or deletions of the host sequences instead
      of the normal 5- or 6-bp duplication.

PMID- 17005709
TI  - Retraction.

PMID- 17005710
TI  - Incidence, clinical characteristics and outcome of congestive heart failure as
      the initial presentation in patients with primary hyperthyroidism.
AB  - BACKGROUND: There are limited systematic data on the incidence, clinical
      characteristics and outcomes of congestive heart failure (CHF) in patients with
      hyperthyroidism. The aim of this study was to investigate the incidence, clinical
      characteristics and outcome of CHF as the initial presentation in patients with
      primary hyperthyroidism. METHODS: The prevalence, clinical characteristics and
      outcome of CHF was studied in 591 consecutive patients (mean (SD) age 45 (1)
      years, 140 men) who presented with primary hyperthyroidism. RESULTS: CHF was the
      presenting condition in 34 patients (5.8%) with hyperthyroidism. The presence of
      atrial fibrillation at presentation (OR 37.4, 95% CI 9.72 to 144.0, p<0.001) was
      an independent predictor for the occurrence of CHF. Of the 34 patients with CHF,
      16 (47%) had systolic left ventricular dysfunction with left ventricular ejection
      fraction (LVEF)<50%. They were predominantly male (OR 26.6, 95% CI 2.6 to 272.5,
      p = 0.006) and had a lower serum thyroxine level (OR 0.93, 95% CI 0.87 to 0.99, p
      = 0.044) than patients with preserved left ventricular systolic function. In
      these patients, LVEF (55 (4)% vs 30 (2)%, p<0.001) and New York Heart Association
      functional class (1.2 (0.1) vs 2.5 (0.2), p<0.001) improved significantly 3
      months after achieving euthyroid status. Systolic left ventricular dysfunction
      (mean (SD) LVEF 38 (4)%) persisted on long-term follow-up in five PATIENTS: no
      clinical parameter could be identified to predict the occurrence of this
      persistent cardiomyopathy (p>0.05). CONCLUSION: CHF was the initial clinical
      presentation in approximately 6% of patients with hyperthyroidism, and half of
      them had left ventricular systolic dysfunction. Symptoms of CHF subsided and LVEF
      improved after treatment for hyperthyroidism. Nonetheless, one-third of these
      patients developed persistent dilated cardiomyopathy.

PMID- 17005711
TI  - Effects of blood pressure on the prothrombotic risk in 1235 patients with non
      valvular atrial fibrillation.
AB  - BACKGROUND: Increased levels of plasma von Willebrand factor (vWf, an index of
      endothelial damage/dysfunction) and soluble P-selectin (sP-sel, an index of
      platelet activation) concentrations have been reported as indices of the
      prothrombotic state in both non-valvular atrial fibrillation and hypertension
      separately. However, the effect of hypertension on the levels of these indices in
      the setting of atrial fibrillation, and whether increasing severity of
      hypertension presents an additive prothrombotic risk, is unclear. METHODS: Plasma
      concentrations of vWf and sP-sel were measured by ELISA in 1235 patients with
      atrial fibrillation, and levels related to a history of hypertension and rising
      quartiles of systolic, diastolic and pulse pressure in those with and without
      diabetes mellitus and prior vascular events. RESULTS: Mean plasma vWf was higher
      among patients with atrial fibrillation with a history of hypertension (149 vs
      145 IU/dl, p = 0.005). Also, an increase in the levels of vWf with increasing
      quartiles of pulse pressure (p = 0.042) was noticed. However, on multivariate
      analysis, after adjusting for potential confounders, the effects of both
      hypertension and pulse pressure became non-significant (p = 0.261 and p = 0.5,
      respectively). Levels of sP-sel were unaffected by a history of hypertension and
      rising quartiles of systolic and diastolic blood pressure, or pulse pressure.
      CONCLUSION: Among patients with atrial fibrillation, patients with hypertension
      have higher vWf levels, indicating endothelial damage/dysfunction, which is
      associated with increasing pulse pressure. However, these associations are
      probably owing to the presence of other associated cardiovascular disease, rather
      than hypertension itself. Furthermore, platelet activation (sP-sel) was unrelated
      to hypertension or blood pressure in this atrial fibrillation cohort.
      Hypertension or blood pressure levels do not seem to have an independent additive
      affect on the prothrombotic state in atrial fibrillation.

PMID- 17005712
TI  - Steroid-eluting stents in patients with acute coronary syndrome: the
      dexamethasone eluting stent Italian registry.
AB  - OBJECTIVE: To assess immediate and mid-term clinical and angiographic outcomes of
      the dexamethasone drug-eluting stent (D-DES) in patients with acute coronary
      syndrome (ACS). PATIENTS AND METHODS: A prospective, nationwide, controlled,
      registry. Inflammation plays a key role in ACS, and the anti-inflammatory effects
      of local elution of dexamethasone in unstable plaques may represent a valid
      therapeutic approach. All patients had ACS on admission (n = 332). 81.5% of the
      patients had unstable angina and 18.5% had non-ST elevation myocardial infarction
      (MI). 47% had ST-T segment changes, 59% had troponin elevation, 77% had elevated
      C-reactive protein levels and 48% had intermediate-high Thrombolysis in
      Myocardial Infarction risk score. Patients were treated according to an early
      invasive approach with 420 D-DES in 387 coronary lesions. Primary end point was
      the cumulative incidence of death, MI and ischaemia-driven target vessel
      revascularisation (TVR) at 6 months. RESULTS: At 30 days, 2 (0.6%) patients died,
      and sub-acute stent thrombosis occurred in 2 patients. At 6 months, 328 (98.8%)
      patients were controlled, 3 (0.9%) patients had died, 7 (2.1%) had MI and 28
      (8.5%) underwent ischaemia-driven TVR. Therefore, the primary end point occurred
      in 11.5% of patients. At multivariate analysis, multi-vessel coronary artery
      disease (odds ratio (OR) = 2.16, 95% CI = 1.47 to 3.17, p = 0.0001) and vessel
      diameter < or =2.75 mm (OR = 1.64, 95% CI = 1.08 to 2.49, p = 0.02) were
      independent predictors of 6-month clinical events. Global angiographic restenosis
      rate was 33.3%. CONCLUSION: This is the first large, multicentre analysis of the
      clinical and angiographic outcomes obtained with D-DES implanted in ACS. D-DES
      offers a low rate of clinical events at 6 months, but has no anti-restenosis
      effect.

PMID- 17005713
TI  - Hepatic changes in the failing Fontan circulation.
AB  - BACKGROUND: The failing Fontan circulation is associated with hepatic impairment.
      The nature of this liver injury is poorly defined. OBJECTIVE: To establish the
      gross and histological liver changes of patients with Fontan circulation relative
      to clinical, biochemical and haemodynamic findings. METHODS: Patients were
      retrospectively assessed for extracardiac Fontan conversion between September
      2003 and June 2005, according to an established clinical protocol. Twelve
      patients, mean age 24.6 (range 15.8-43.4) years were identified. The mean
      duration since the initial Fontan procedure was 14.1 (range 6.9-26.4) years.
      RESULTS: Zonal enhancement of the liver (4/12) on CT was more common in patients
      with lower hepatic vein pressures (p = 0.007), and in those with absent cardiac
      cirrhosis on histological examination (p = 0.033). Gastro-oesophageal varices
      (4/12) were more common in patients with higher hepatic vein pressure (21 (6.3)
      vs 12.2 (2.2) mm Hg, p = 0.013) and associated with more advanced cirrhosis (p =
      0.037). The extent of cirrhosis (7/12) was positively correlated with the hepatic
      vein pressure (r = 0.83, p = 0.003). A significant positive correlation was found
      between the Fontan duration and the degree of hepatic fibrosis (r = 0.75, p =
      0.013), as well as presence of broad scars (r = 0.71, p = 0.021). Protein-losing
      enteropathy (5/12) occurred more frequently in patients with longer Fontan
      duration (11.7 (3.2) vs 17.9 (6.1) years, p = 0.038). CONCLUSIONS: Liver injury,
      which can be extensive in this patient group, is related to Fontan duration and
      hepatic vein pressures. CT scan assists non-invasive assessment. Cardiac
      cirrhosis with the risk of developing gastro-oesophageal varices and regenerative
      liver nodules, a precursor to hepatocellular carcinoma, is common in this patient
      group.

PMID- 17005714
TI  - Logistic, additive or historical: is EuroSCORE an appropriate model for comparing
      individual surgeons' performance?
AB  - Both versions of the EuroSCORE, the complex logistic and the simpler additive,
      have been used for comparing institutional performance, but they are no longer
      robust enough to be used for comparing individual surgeons. It is now time to
      tighten the standard and add additional data to obtain a more holistic picture of
      the quality of cardiac surgical care in the UK.

PMID- 17005716
TI  - Phasic changes in arterial blood volume is influenced by collateral blood flow:
      implications for the quantification of coronary stenosis at rest.
AB  - BACKGROUND: The systolic to diastolic arteriolar blood volume (aBV) ratio derived
      using myocardial contrast echocardiography (MCE) can identify the presence of
      coronary stenosis at rest. There are some patients with moderate to severe
      coronary stenosis who nonetheless exhibit a normal systolic to disatolic aBV
      ratio. AIM: To test the hypothesis that collateral blood flow influences the
      systolic to diastolic aBV ratio. MCE-defined phasic changes in aBV were recorded
      at baseline and up to 2 degrees of non-critical stenosis in 12 dogs. Measurements
      were made from MCE-defined collateralised and non-collateralised portions of the
      left anterior descending arterial bed. RESULTS: Increases in both systolic and
      diastolic aBV were noted in the non-collateralised region with increasing degrees
      of stenosis. Although these increases in the absolute values did not reach
      statistical significance, the systolic to diastolic aBV signal ratio in the non
      collateralised bed increased significantly between stages (analysis of variance,
      p = 0.003). In comparison, in the collateralised bed neither the absolute
      systolic nor diastolic aBV signals changed with increasing degrees of stenosis.
      Consequently, the aBV signal ratio between systole and diastole also did not
      change in this bed. CONCLUSION: Phasic changes in aBV are influenced by the
      degree of collateral blood flow. Thus, if the region of interest is not placed in
      the centre of the vascular bed, the degree of stenosis may be underestimated by
      the systolic to diastolic aBV ratio. On the other hand, as extensive
      collateralisation may indicate excellent prognosis, this ratio may provide
      prognostic information independent of the coronary anatomy.

PMID- 17005715
TI  - Limitations of the New York Heart Association functional classification system
      and self-reported walking distances in chronic heart failure.
AB  - BACKGROUND: Two ways to evaluate the symptoms of heart failure are the New York
      Heart Association (NYHA) classification and asking patients how far they can walk
      (walk distance). The NYHA system is commonly used, although it is not clear how
      individual clinicians apply it. AIM: To investigate how useful these measures are
      to assess heart failure and whether other questions might be more helpful.
      METHODS: 30 cardiologists were asked what questions they used when assessing
      patients with heart failure. To assess interoperator variability, two
      cardiologists assessed a series of 50 patients in classes II and III using the
      NYHA classification. 45 patients who had undergone cardiopulmonary testing were
      interviewed using a specially formulated questionnaire. They were also asked how
      far they could walk before being stopped by symptoms, and then tested on their
      ability to estimate distance. RESULTS: The survey of cardiologists showed no
      consistent method for assessing NYHA class and a literature survey showed that
      99% of research papers do not reference or describe their methods for assigning
      NYHA classes. The interoperator variability study showed only 54% concordance
      between the two cardiologists. 70% of cardiologists asked patients for their walk
      distance; however, this walk distance correlated poorly with actual exercise
      capacity measured by cardiopulmonary testing (rho = 0.04, p = 0.82). CONCLUSION:
      No consistent method of assessing NYHA class is in use and the interoperator
      study on class II and class III patients gave a result little better than chance.
      Some potential questions are offered for use in assessment. Walking distance,
      although frequently asked, does not correlate with formally measured exercise
      capacity, even after correction for patient perception of distance, and has never
      been found to have prognostic relevance. Its value is therefore doubtful.

PMID- 17005717
TI  - Synaptically released zinc gates long-term potentiation in fear conditioning
      pathways.
AB  - The functional role of releasable Zn2+ in the central nervous system remains
      unknown. Here we show that zinc transporter 3 (ZnT-3), which maintains a high
      concentration of Zn2+ in synaptic vesicles and serves as a marker for zinc
      containing neurons, is enriched in the lateral nucleus of the amygdala and in the
      temporal area 3 of the auditory cortex, an area that conveys information about
      the auditory conditioned stimulus to the lateral nucleus of the amygdala, but not
      in other conditioned stimulus areas located in the auditory thalamus. Using whole
      cell recordings from amygdala slices, we demonstrated that activity-dependent
      release of chelatable Zn2+ is required for the induction of spike timing
      dependent long-term potentiation in cortical input to the amygdala implicated in
      fear learning. Our data indicate that synaptically released Zn2+ enables long
      term potentiation at the cortico-amygdala synapses by depressing feed-forward
      GABAergic inhibition of principal neurons. This regulatory mechanism, implicating
      pathway-dependent release of Zn2+, may serve an essential control function in
      assuring spatial specificity of long-lasting synaptic modifications in the neural
      circuit of a learned behavior.

PMID- 17005718
TI  - Protein kinase A regulates RNA polymerase III transcription through the nuclear
      localization of Maf1.
AB  - Maf1 is an essential and specific mediator of transcriptional repression in the
      RNA polymerase (pol) III system. Maf1-dependent repression occurs in response to
      a wide range of conditions, suggesting that the protein itself is targeted by the
      major nutritional and stress-signaling pathways. We show that Maf1 is a substrate
      for cAMP-dependent PKA in vitro and is differentially phosphorylated on PKA sites
      in vivo under normal versus repressing conditions. PKA activity negatively
      regulates Maf1 function because strains with unregulated high PKA activity block
      repression of pol III transcription in vivo, and strains lacking all PKA activity
      are hyperrepressible. Nuclear accumulation of Maf1 is required for
      transcriptional repression and is regulated by two nuclear localization sequences
      in the protein. An analysis of PKA phosphosite mutants shows that the
      localization of Maf1 is affected via the N-terminal nuclear localization
      sequence. In particular, mutations that prevent phosphorylation at PKA consensus
      sites promote nuclear accumulation of Maf1 without inducing repression. These
      results indicate that negative regulation of Maf1 by PKA is achieved by
      inhibiting its nuclear import and suggest that a PKA-independent activation step
      is required for nuclear Maf1 to function in the repression of pol III
      transcription. Finally, we report a previously undescribed phenotype for Maf1 in
      tRNA gene-mediated silencing of nearby RNA pol II transcription.

PMID- 17005719
TI  - A purified Bacillus thuringiensis crystal protein with therapeutic activity
      against the hookworm parasite Ancylostoma ceylanicum.
AB  - Crystal (Cry) proteins produced by the soil bacterium Bacillus thuringiensis (Bt)
      are harmless to vertebrates, but they are highly toxic to insects and nematodes.
      Their value in controlling insects that destroy crops and transmit human diseases
      is well established. Although it has recently been demonstrated that a few
      individual Bt Cry proteins, such as Cry5B, are toxic to a wide range of free
      living nematodes, the potential activity of purified Cry proteins against
      parasitic nematodes remains largely unknown. We report here studies aimed at
      characterizing in vitro and in vivo anthelminthic activities of purified
      recombinant Cry5B against the hookworm parasite Ancylostoma ceylanicum, a
      bloodfeeding gastrointestinal nematode for which humans are permissive hosts. By
      using in vitro larval development assays, Cry5B was found to be highly toxic to
      early stage hookworm larvae. Exposure of adult A. ceylanicum to Cry5B was also
      associated with significant toxicity, including a substantial reduction in egg
      excretion by adult female worms. To demonstrate therapeutic efficacy in vivo,
      hamsters infected with A. ceylanicum were treated with three daily oral doses of
      purified Cry5B, the benzimidazole anthelminthic mebendazole, or buffer. Compared
      with control (buffer-treated) animals, infected hamsters that received Cry5B
      showed statistically significant improvements in growth and blood hemoglobin
      levels as well as reduced worm burdens that were comparable to the mebendazole
      treated animals. These data demonstrate that Cry5B is highly active in vitro and
      in vivo against a globally significant nematode parasite and that Cry5B warrants
      further clinical development for human and veterinary use.

PMID- 17005720
TI  - Molecular analysis of mitotic chromosome condensation using a quantitative time
      resolved fluorescence microscopy assay.
AB  - Chromosomes condense during mitotic entry to facilitate their segregation.
      Condensation is typically assayed in fixed preparations, limiting analysis of
      contributing factors. Here, we describe a quantitative method to monitor
      condensation kinetics in living cells expressing GFP fused to a core histone. We
      demonstrate the utility of this method by using it to analyze the molecular
      requirements for the condensation of holocentric chromosomes during the first
      division of the Caenorhabditis elegans embryo. In control embryos, the
      fluorescence intensity distribution for nuclear GFP:histone changes during two
      distinct time intervals separated by a plateau phase. During the first interval,
      primary condensation converts diffuse chromatin into discrete linear chromosomes.
      After the plateau, secondary condensation compacts the curvilinear chromosomes to
      form shorter bar-shaped structures. We quantitatively compared the consequences
      on this characteristic profile of depleting the condensin complex, the mitosis
      specific histone H3 kinase Aurora B, the centromeric histone CENP-A, and CENP-C,
      a conserved protein required for kinetochore assembly. Both condensin and CENP-A
      play critical but distinct roles in primary condensation. In contrast, depletion
      of CENP-C slows but does not prevent primary condensation. Finally, Aurora B
      inhibition has no effect on primary condensation, but slightly delays secondary
      condensation. These results provide insights into the process of condensation,
      help resolve apparent contradictions from prior studies, and indicate that CENP-A
      chromatin has an intrinsic role in the condensation of holocentric chromosomes
      that is independent of its requirement for kinetochore assembly.

PMID- 17005721
TI  - piggyBac is a flexible and highly active transposon as compared to sleeping
      beauty, Tol2, and Mos1 in mammalian cells.
AB  - A nonviral vector for highly efficient site-specific integration would be
      desirable for many applications in transgenesis, including gene therapy. In this
      study we directly compared the genomic integration efficiencies of piggyBac,
      hyperactive Sleeping Beauty (SB11), Tol2, and Mos1 in four mammalian cell lines.
      piggyBac demonstrated significantly higher transposition activity in all cell
      lines whereas Mos1 had no activity. Furthermore, piggyBac transposase coupled to
      the GAL4 DNA-binding domain retains transposition activity whereas similarly
      manipulated gene products of Tol2 and SB11 were inactive. The high transposition
      activity of piggyBac and the flexibility for molecular modification of its
      transposase suggest the possibility of using it routinely for mammalian
      transgenesis.

PMID- 17005723
TI  - Activation, internalization, and recycling of the serotonin 2A receptor by
      dopamine.
AB  - Serotonergic and dopaminergic systems, and their functional interactions, have
      been implicated in the pathophysiology of various CNS disorders. Here, we use
      recombinant serotonin (5-HT) 2A (5-HT2A) receptors to further investigate direct
      interactions between dopamine and 5-HT receptors. Previous studies in Xenopus
      oocytes showed that dopamine, although not the cognate ligand for the 5-HT2A
      receptor, acts as a partial-efficacy agonist. At micromolar concentrations,
      dopamine also acts as a partial-efficacy agonist on 5-HT2A receptors in HEK293
      cells. Like 5-HT, dopamine also induces receptor-internalization in these cells,
      although at significantly higher concentrations than 5-HT. Interestingly, if the
      receptors are first sensitized or "primed" by subthreshold concentrations of 5
      HT, then dopamine-induced internalization occurs at concentrations approximately
      10-fold lower than when dopamine is used alone. Furthermore, unlike 5-HT-mediated
      internalization, dopamine-mediated receptor internalization, alone, or after
      sensitization by 5-HT, does not depend on PKC. Dopamine-internalized receptors
      recycle to the surface at rates similar to those of 5-HT-internalized receptors.
      Our results suggest a previously uncharacterized role for dopamine in the direct
      activation and internalization of 5-HT2A receptors that may have clinical
      relevance to the function of serotonergic systems in anxiety, depression, and
      schizophrenia and also to the treatment of these disorders.

PMID- 17005722
TI  - Casein kinase 2 (CK2) increases survivin expression via enhanced beta-catenin-T
      cell factor/lymphoid enhancer binding factor-dependent transcription.
AB  - Increased expression of casein kinase 2 (CK2) is associated with
      hyperproliferation and suppression of apoptosis in cancer. Mutations in the tumor
      suppressor APC (adenomatous polyposis coli) are frequent in colon cancer and
      often augment beta-catenin-T cell factor (Tcf)/lymphoid enhancer binding factor
      (Lef)-dependent transcription of genes such as c-myc and cyclin-D1. CK2 has also
      been implicated recently in the regulation of beta-catenin stability. To identify
      mechanisms by which CK2 promotes survival, effects of the specific CK2 inhibitors
      4,5,6,7-tetrabromobenzotriazole (TBB) and 2-dimethylamino-4,5,6,7-tetrabromo-1H
      benzimidazole were assessed. TBB and 2-dimethylamino-4,5,6,7-tetrabromo-1H
      benzimidazole significantly decreased proliferation and increased apoptosis of
      HT29(US) colon cancer cells. RT-PCR and immunoblot analysis revealed that both
      inhibitors decreased survivin mRNA and protein levels in HT29(US) cells. Similar
      effects were observed with TBB in human DLD-1 and SW-480 colorectal cells as well
      as ZR-75 breast cancer cells and HEK-293T embryonic kidney cells. Expression of
      GFP-CK2alpha in HEK-293T cells resulted in beta-catenin-Tcf/Lef-dependent up
      regulation of survivin and increased resistance to anticancer drugs. Augmented
      beta-catenin-Tcf/Lef-dependent transcription and resistance to apoptosis observed
      upon GFP-CK2alpha expression were abolished by TBB. Alternatively, HEK-293T cells
      expressing GFP-survivin were resistant to TBB-induced apoptosis. Finally, siRNA
      mediated down-regulation of CK2alpha in HEK-293T cells coincided with reduced
      beta-catenin and survivin levels. Taken together, these results suggest that CK2
      kinase activity promotes survival by increasing survivin expression via beta
      catenin-Tcf/Lef-mediated transcription. Hence, selective CK2 inhibition or down
      regulation in tumors may provide an attractive opportunity for the development of
      novel cancer therapies.

PMID- 17005724
TI  - Nucleolar trafficking is essential for nuclear export of intronless herpesvirus
      mRNA.
AB  - The nucleolus is the largest subnuclear structure and is plurifunctional in
      nature. Here, we demonstrate that nucleolar localization of a key herpesvirus
      regulatory protein is essential for its role in virus mRNA nuclear export. The
      herpesvirus saimiri ORF57 protein is a nucleocytoplasmic shuttle protein that is
      conserved in all herpesviruses and orchestrates the nuclear export of viral
      intronless mRNAs. We demonstrate that expression of the ORF57 protein induces
      nucleolar redistribution of human TREX (transcription/export) proteins that are
      involved in mRNA nuclear export. Moreover, we describe a previously unidentified
      nucleolar localization signal within ORF57 that is composed of two distinct
      nuclear localization signals. Intriguingly, point mutations that ablate ORF57
      nucleolar localization lead to a failure of ORF57-mediated viral mRNA nuclear
      export. Furthermore, nucleolar retargeting of the ORF57 mutant was achieved by
      the incorporation of the HIV-1 Rev nucleolar localization signal, and analysis
      demonstrated that this modification was sufficient to restore viral mRNA nuclear
      export. This finding represents a unique and fundamental role for the nucleolus
      in nuclear export of viral mRNA.

PMID- 17005725
TI  - Midgut bacteria required for Bacillus thuringiensis insecticidal activity.
AB  - Bacillus thuringiensis is the most widely applied biological insecticide and is
      used to manage insects that affect forestry and agriculture and transmit human
      and animal pathogens. This ubiquitous spore-forming bacterium kills insect larvae
      largely through the action of insecticidal crystal proteins and is commonly
      deployed as a direct bacterial spray. Moreover, plants engineered with the cry
      genes encoding the B. thuringiensis crystal proteins are the most widely
      cultivated transgenic crops. For decades, the mechanism of insect killing has
      been assumed to be toxin-mediated lysis of the gut epithelial cells, which leads
      to starvation, or B. thuringiensis septicemia. Here, we report that B.
      thuringiensis does not kill larvae of the gypsy moth in the absence of indigenous
      midgut bacteria. Elimination of the gut microbial community by oral
      administration of antibiotics abolished B. thuringiensis insecticidal activity,
      and reestablishment of an Enterobacter sp. that normally resides in the midgut
      microbial community restored B. thuringiensis-mediated killing. Escherichia coli
      engineered to produce the B. thuringiensis insecticidal toxin killed gypsy moth
      larvae irrespective of the presence of other bacteria in the midgut. However,
      when the engineered E. coli was heat-killed and then fed to the larvae, the
      larvae did not die in the absence of the indigenous midgut bacteria. E. coli and
      the Enterobacter sp. achieved high populations in hemolymph, in contrast to B.
      thuringiensis, which appeared to die in hemolymph. Our results demonstrate that
      B. thuringiensis-induced mortality depends on enteric bacteria.

PMID- 17005726
TI  - Mitochondria-related male infertility.
AB  - Approximately 15% of human couples are affected by infertility, and about half of
      these cases of infertility can be attributed to men, through low sperm motility
      (asthenozoospermia) or/and numbers (oligospermia). Because mitochondrial genome
      (mtDNA) mutations are identified in patients with fertility problems, there is a
      possibility that mitochondrial respiration defects contribute to male
      infertility. To address this possibility, we used a transmitochondrial mouse
      model (mito-mice) carrying wild-type mtDNA and mutant mtDNA with a pathogenic
      4,696-bp deletion (DeltamtDNA). Here we show that mitochondrial respiration
      defects caused by the accumulation of DeltamtDNA induced oligospermia and
      asthenozoospermia in the mito-mice. Most sperm from the infertile mito-mice had
      abnormalities in the middle piece and nucleus. Testes of the infertile mito-mice
      showed meiotic arrest at the zygotene stage as well as enhanced apoptosis. Thus,
      our in vivo study using mito-mice directly demonstrates that normal mitochondrial
      respiration is required for mammalian spermatogenesis, and its defects resulting
      from accumulated mutant mtDNAs cause male infertility.

PMID- 17005727
TI  - Separate encoding of identity and similarity of complex familiar odors in
      piriform cortex.
AB  - Piriform cortical circuits are hypothesized to form perceptions from responses to
      specific odorant features, but the anterior piriform cortex (aPCX) and posterior
      piriform cortex (pPCX) differ markedly in their anatomical organization,
      differences that could lead to distinct roles in odor encoding. Here, we tested
      whether experience with a complex odorant mixture would modify encoding of the
      mixture and its components in aPCX and pPCX. Rats were exposed to an odorant
      mixture and its components in a go/no-go rewarded odor discrimination task. After
      reaching behavioral performance criterion, single-unit recordings were made from
      the aPCX and pPCX in these rats and in odor-naive, control, urethane-anesthetized
      rats. After odor experience, aPCX neurons were more narrowly tuned to the test
      odorants, and there was a decorrelation in aPCX population responses to the
      mixture and its components, suggesting a more distinct encoding of the familiar
      mixture from its components. In contrast, pPCX neurons were more broadly tuned to
      the familiar odorants, and pPCX population responses to the mixture and its
      components became more highly correlated, suggesting a pPCX encoding of
      similarity between familiar stimuli. The results suggest aPCX and pPCX play
      different roles in the processing of familiar odors and are consistent with an
      experience-dependent encoding (perceptual learning) of synthetic odorant identity
      in aPCX and an experience-dependent encoding of odor similarity or odor quality
      in pPCX.

PMID- 17005728
TI  - GABAA receptor alpha 4 subunits mediate extrasynaptic inhibition in thalamus and
      dentate gyrus and the action of gaboxadol.
AB  - The neurotransmitter GABA mediates the majority of rapid inhibition in the CNS.
      Inhibition can occur via the conventional mechanism, the transient activation of
      subsynaptic GABAA receptors (GABAA-Rs), or via continuous activation of high
      affinity receptors by low concentrations of ambient GABA, leading to "tonic"
      inhibition that can control levels of excitability and network activity. The
      GABAA-R alpha4 subunit is expressed at high levels in the dentate gyrus and
      thalamus and is suspected to contribute to extrasynaptic GABAA-R-mediated tonic
      inhibition. Mice were engineered to lack the alpha4 subunit by targeted
      disruption of the Gabra4 gene. alpha4 Subunit knockout mice are viable, breed
      normally, and are superficially indistinguishable from WT mice. In
      electrophysiological recordings, these mice show a lack of tonic inhibition in
      dentate granule cells and thalamic relay neurons. Behaviorally, knockout mice are
      insensitive to the ataxic, sedative, and analgesic effects of the novel hypnotic
      drug, gaboxadol. These data demonstrate that tonic inhibition in dentate granule
      cells and thalamic relay neurons is mediated by extrasynaptic GABAA-Rs containing
      the alpha4 subunit and that gaboxadol achieves its effects via the activation of
      this GABAA-R subtype.

PMID- 17005730
TI  - Encapsulation of a reactive core in neuromelanin.

PMID- 17005729
TI  - Tumors reveal their secrets to cytotoxic T cells.

PMID- 17005731
TI  - Diagnostic value of Elisa serological tests in childhood tuberculosis.
AB  - Two separate studies (study I and study II) were conducted to evaluate the
      efficacy of ELISA serological test for the detection of IgG antibodies against
      specific glycolipid antigen (PGLTb1) and ESAT 6 antigen of Mycobacterium
      tuberculosis, respectively. These results were compared with bacteriological
      tests [Ziehl Neelson (ZN) staining for acid-fast bacilli and culture on
      Lowenstein Jensen (LJ) medium] and polymerase chain reaction (PCR) targeting
      IS6110 sequence. Both studies were carried out on children with pulmonary,
      central nervous system, lymph node, and gastrointestinal tuberculosis along with
      matching controls (65 cases and 27 controls for study I and 83 cases and 22
      controls for study II). Informed consents of their parents or guardians were
      taken. They were subjected to clinical examination, relevant laboratory
      investigations, tuberculin test and chest radiograph. Relevant body fluids were
      subjected to bacteriological tests and PCR. Sera samples were analyzed for
      antibodies against PGLTbl and ESAT 6 antigen in study I and study II,
      respectively. ELISA tests showed a significantly higher sensitivity (49% study I;
      53%, study II) as compared with LJ medium culture method (15.4%, study I; 28.9%
      study II) and ZN staining (27.7%, study I; 20.5%, study II) in all patients (p <
      0.05). The results were comparable with PCR (40%, study I; 42.2% study II).
      Specificity of ELISA test was 100% in all the patients except in those with
      pulmonary disease (92.8%, study I; 84.8%, study II). In view of the convenience,
      low cost and comparable sensitivity with PCR, these ELISA tests have a promising
      future in the diagnosis of childhood tuberculosis.

PMID- 17005732
TI  - Bacterial safety of flash-heated and unheated expressed breastmilk during
      storage.
AB  - Heat-treated breastmilk is one infant-feeding option recommended by the WHO to
      reduce mother-to-child transmission of HIV in developing countries. Flash-heat, a
      simple pasteurization method that a mother could perform in her home, has been
      shown to inactivate cell-free HIV-1. Since heating may affect the naturally
      occurring antimicrobial properties found in breastmilk, storing heated breastmilk
      may present a safety issue in resource-poor settings due to lack of refrigeration
      and potential contamination. To address this, we investigated the ability of
      flash-heat to eliminate bacteria and to prevent growth over time compared with
      unheated breastmilk. We collected breastmilk samples from 38 HIV positive mothers
      in South Africa and aliquoted them to flash-heated and unheated controls. Samples
      were stored at room temperature for 0, 2, 6 and 8 h and then plated and incubated
      for 24 h at 37 degrees C in CO(2). We performed total colony counts and
      identified Escherichia coli, Staphylocuccus aureus and Group A and Group B
      streptococci. Unheated samples had a significantly higher number of samples
      positive for bacterial growth at each time point (p < 0.0001), as well as mean
      colony-forming units (CFU)/ml in those samples that were positive at each time
      point (p < 0.0001). In addition, unheated samples had a significantly higher rate
      of bacterial propagation over time than flash-heated samples when comparing log
      values of CFU/ml across 0-8 h (p < 0.005). No pathogenic growth was observed in
      the flash-heated samples, while the unheated samples showed growth of E. coli (n
      = 1) and S. aureus (n = 6). Our data suggest that storage of flash-heated
      breastmilk is safe at room temperature for up to 8 h.

PMID- 17005733
TI  - False-positive result from a Bayer Versant human immunodeficiency virus type 1
      branched-DNA viral load assay, with a possible role for light leakage after
      inadequate maintenance of the analyzer.

PMID- 17005734
TI  - Emergence of a unique multiply-antibiotic-resistant Streptococcus pneumoniae
      serotype 7B clone in Dhaka, Bangladesh.

PMID- 17005735
TI  - Presence of new mecA and mph(C) variants conferring antibiotic resistance in
      Staphylococcus spp. isolated from the skin of horses before and after clinic
      admission.
AB  - Because of the frequency of multiple antibiotic resistance, Staphylococcus
      species often represent a challenge in incisional infections of horses undergoing
      colic surgery. To investigate the evolution of antibiotic resistance patterns
      before and after preventative peri- and postoperative penicillin treatment,
      staphylococci were isolated from skin and wound samples at different times during
      hospitalization. Most staphylococci were normal skin commensals and belonged to
      the common coagulase-negative group. In some cases they turned out to be
      opportunistic pathogens present in wound infections. MICs were determined for 12
      antibiotics, and antibiotic resistance genes were detected by microarray. At
      hospital admission, horses harbored staphylococci that were susceptible to
      antibiotics or resistant to one group of drugs, mainly due to the presence of new
      variants of the methicillin and macrolide resistance genes mecA and mph(C),
      respectively. After 3 days, the percentage of Staphylococcus isolates displaying
      antibiotic resistance, as well as the number of resistance genes per isolate,
      increased moderately in hospitalized horses without surgery or penicillin
      treatment but dramatically in hospitalized horses after colic surgery as well as
      penicillin treatment. Staphylococcus species displaying multiple resistance were
      found to harbor mainly genes conferring resistance to beta-lactams (mecA and
      blaZ), aminoglycosides [str and aac(6')-Ie-aph(2')-Ia], and trimethoprim [dfr(A)
      and dfr(D)]. Additional genes conferring resistance to macrolides [mph(C),
      erm(C), and erm(B)], tetracycline [tet(K) and tet(M)], chloramphenicol
      [cat(pC221) and cat(pC223)], and streptothricin (sat4) appeared in several
      strains. Hospitalization and preventive penicillin use were shown to act as
      selection agents for multidrug-resistant commensal staphylococcal flora.

PMID- 17005736
TI  - Evidence supporting zoonotic transmission of Cryptosporidium spp. in Wisconsin.
AB  - Cryptosporidium hominis and Cryptosporidium parvum are the primary species of
      Cryptosporidium that infect humans. C. hominis has an anthroponotic transmission
      cycle, while C. parvum is zoonotic, infecting cattle and other ruminants, in
      addition to humans. Most cryptosporidiosis outbreaks in the United States have
      been caused by C. hominis, and this species is often reported as the primary
      cause of cryptosporidiosis in this country. However, outbreaks account for only
      10% of the overall cryptosporidiosis cases, and there are few data on the species
      that cause sporadic cases. The present study identified the species/genotypes and
      subgenotypes of Cryptosporidium in 49 cases of sporadic cryptosporidiosis in
      Wisconsin during the period from 2003 to 2005. The species/genotype of isolates
      was determined by PCR restriction fragment length polymorphism analysis of the
      18S rRNA and Cryptosporidium oocyst wall protein genes. The C. parvum and C.
      hominis isolates were subgenotyped by sequence analysis of the GP60 gene. Forty
      four of 49 isolates were identified as C. parvum, and 1 was identified as C.
      hominis. Of the remaining isolates, one was identified as being of the cervine
      genotype, one was identified as being a cervine genotype variant, and two were
      identified as being of a novel human genotype, previously reported as W17. Nine
      different subgenotypes were identified within the C. parvum species, and two of
      these were responsible for 60% of the cases. In this study we found that most
      sporadic cases of cryptosporidiosis in Wisconsin are caused by zoonotic
      Cryptosporidium species, indicating that zoonotic transmission could be more
      frequently associated with sporadic cases in the United States.

PMID- 17005737
TI  - Use of the BACTEC Mycobacteria Growth Indicator Tube 960 automated system for
      recovery of Mycobacteria from 9,558 extrapulmonary specimens, including urine
      samples.
AB  - The BACTEC Mycobacteria Growth Indicator Tube 960 (MGIT 960) system was applied
      for recovery of mycobacteria from extrapulmonary specimens and compared with
      solid media (Lowenstein-Jensen and Stonebrink). A total of 9,558 specimens were
      investigated, comprising 3,074 body fluids, 1,878 tissues, and 2,069 urine
      samples, from which the recovery of mycobacteria was not yet established for MGIT
      960. In total, the MGIT 960 was able to detect 446 (90.3%) of the 494 isolates of
      Mycobacterium tuberculosis complex (MTBC) and 223 (86.0%) out of the 259 isolates
      of nontuberculous mycobacteria (NTM). In comparison to this, culture on solid
      medium revealed 358 (72.6%) MTBC isolates and 164 (66.8%) NTM isolates. While 136
      (27.6%) of the MTBC isolates and 95 (19.2%) of the NTM isolates were recovered
      from the MGIT 960 only, 48 (9.7%) of the MTBC isolates and 36 (13.9%) NTM
      isolates grew only on solid media. Thus, the overall sensitivities for the
      recovery of mycobacteria from extrapulmonary specimens with MGIT 960 and solid
      media were 88.8% and 69.3%, respectively. However, the efficiency of the MGIT 960
      system can be maximized with additional culture on solid media.

PMID- 17005738
TI  - Optimizing antigen cocktails for detection of Mycobacterium bovis in herds with
      different prevalences of bovine tuberculosis: ESAT6-CFP10 mixture shows optimal
      sensitivity and specificity.
AB  - Bovine tuberculosis is a major problem in many countries; hence, new and better
      diagnostic tools are urgently needed. In this work, we have tested ESAT6, CFP10,
      PE13, PE5, MPB70, TB10.4, and TB27.4 for their potentials as diagnostic markers
      in field animals from Northern Ireland, Mexico, and Argentina, regions with low,
      medium, and high prevalences of bovine tuberculosis, respectively. At all three
      sites, ESAT6 and CFP10 were superior diagnostic antigens, while their combination
      performed even better at the two sites where the combination was tested,
      providing the best coverage for the detection of diseased populations. The high
      sensitivity in the skin test reactor groups, combined with the high specificity
      in the tuberculosis-free groups, indicated that a diagnosis could correctly be
      made for 85% of the infected animals, based on their responses to these two
      antigens. Furthermore, TB10.4, PE13, and PE5 have the potential to supplement
      ESAT6 and CFP10 in a future five-component diagnostic cocktail.

PMID- 17005740
TI  - Emergence of non-ceftriaxone-susceptible Neisseria meningitidis in India.

PMID- 17005739
TI  - Neurologic disease in captive lions (Panthera leo) with low-titer lion lentivirus
      infection.
AB  - Lion lentivirus (LLV; also known as feline immunodeficiency virus of lion,
      Panthera leo [FIVPle]) is present in free-ranging and captive lion populations at
      a seroprevalence of up to 100%; however, clinical signs are rarely reported. LLV
      displays up to 25% interclade sequence diversity, suggesting that it has been in
      the lion population for some time and may be significantly host adapted. Three
      captive lions diagnosed with LLV infection displayed lymphocyte subset
      alterations and progressive behavioral, locomotor, and neuroanatomic
      abnormalities. No evidence of infection with other potential neuropathogens was
      found. Antemortem electrodiagnostics and radiologic imaging indicated a diagnosis
      consistent with lentiviral neuropathy. PCR was used to determine a partial
      lentiviral genomic sequence and to quantify the proviral burden in eight
      postmortem tissue specimens. Phylogenetic analysis demonstrated that the virus
      was consistent with the LLV detected in other captive and free-ranging lions.
      Despite progressive neurologic signs, the proviral load in tissues, including
      several regions of the brain, was low; furthermore, gross and histopathologic
      changes in the brain were minimal. These findings suggest that the symptoms in
      these animals resulted from nonspecific encephalopathy, similar to human
      immunodeficiency virus, FIV, and simian immunodeficiency virus (SIV)
      neuropathies, rather than a direct effect of active viral replication. The
      association of neuropathy and lymphocyte subset alterations with chronic LLV
      infection suggests that long-term LLV infection can have detrimental effects for
      the host, including death. This is similar to reports of aged sootey mangabeys
      dying from diseases typically associated with end-stage SIV infection and
      indicates areas for further research of lentiviral infections of seemingly
      adapted natural hosts, including mechanisms of host control and viral adaptation.

PMID- 17005741
TI  - Development and evaluation of reverse transcription-loop-mediated isothermal
      amplification assay for rapid and real-time detection of Japanese encephalitis
      virus.
AB  - The standardization and validation of a one-step, single-tube accelerated
      quantitative reverse transcription-loop-mediated isothermal amplification (RT
      LAMP) assay is reported for rapid and real-time detection of Japanese
      encephalitis virus (JEV). The RT-LAMP assay reported in this study is very simple
      and rapid; the amplification can be obtained in 30 min under isothermal
      conditions at 63 degrees C by employing a set of six primers targeting the E gene
      of JEV. The RT-LAMP assay demonstrated exceptionally higher sensitivity compared
      to that of RT-PCR, with a detection limit of 0.1 PFU. The specificities of the
      selected primer sets were established by cross-reactivity studies with other
      closely related members of the JEV serocomplex as well as by evaluation of
      healthy human volunteers. The comparative evaluation of the RT-LAMP assay for
      clinical diagnosis with a limited number of patient cerebrospinal fluid samples
      revealed 85% concordance with conventional RT-PCR, with a sensitivity and a
      specificity of 100% and 86%, respectively. The concentration of virus in most of
      the clinical samples was 10(2) to 10(5) PFU/ml, as determined from the standard
      curve based on the time of positivity in the samples. In addition, the monitoring
      of gene amplification can also be visualized with the naked eye by using SYBR
      green I fluorescent dye. Thus, due to easy operation without a requirement of
      sophisticated equipment and skilled personnel, the RT-LAMP assay reported here is
      a valuable tool for the rapid and real-time detection of JEV not only by well
      equipped laboratories but also by peripheral diagnostic laboratories with limited
      financial resources in developing countries.

PMID- 17005742
TI  - Association of ocular toxoplasmosis with type I Toxoplasma gondii strains: direct
      genotyping from peripheral blood samples.
AB  - Toxoplasma gondii strains were genotyped directly from blood samples of patients
      with ocular toxoplasmosis. Analysis of nontranscribed spacer 2 revealed that all
      detected strains belonged to type I, suggesting an association of ocular
      toxoplasmosis with this type. The method shows the usefulness of blood samples
      for genotyping in ocular toxoplasmosis.

PMID- 17005743
TI  - Identification of a novel, invasive, not-yet-cultivated Treponema sp. in the
      large intestine of pigs by PCR amplification of the 16S rRNA gene.
AB  - Laser capture microdissection in combination with fluorescent in situ
      hybridization was used to identify an unknown species of spirochetes from the pig
      colonic mucosa. The 16S rRNA gene was PCR amplified, and the closest related type
      strain was Treponema bryantiiT (90.1%). The spirochete, here named "Candidatus
      Treponema suis," was associated with colitis, including invasion of the surface
      epithelium as well as superficial parts of the mucosa.

PMID- 17005744
TI  - Report of two cases of aseptic meningitis with persistence of pneumococcal cell
      wall components in cerebrospinal fluid after Pneumococcal meningitis.
AB  - We describe two cases of aseptic meningitis occurring some time after
      pneumococcal meningitis. Both cases may have resulted from an inflammatory
      response to persistent pneumococcal cell membrane components, as the
      cerebrospinal fluid samples were positive by the Binax NOW Streptococcus
      pneumoniae antigen test. Potential mechanisms and diagnostic impact are
      discussed.

PMID- 17005745
TI  - Identification of new genetic regions more prevalent in nontypeable Haemophilus
      influenzae otitis media strains than in throat strains.
AB  - Nontypeable (NT) Haemophilus influenzae strains cause significant respiratory
      illness and are isolated from up to half of middle ear aspirates from children
      with acute otitis media. Previous studies have identified two genes, lic2B and
      hmwA, that are associated with NT H. influenzae strains isolated from the middle
      ears of children with otitis media but that are not associated with NT H.
      influenzae strains isolated from the throats of healthy children, suggesting that
      they may play a role in virulence in otitis media. In this study, genomic
      subtraction was used to identify additional genetic regions unique to middle ear
      strains. The genome of NT H. influenzae middle ear strain G622 was subtracted
      from that of NT H. influenzae throat strain 23221, and the resultant gene regions
      unique to the middle ear strain were identified. Subsequently, the relative
      prevalence of the middle ear-specific gene regions among a large panel of otitis
      media and throat strains was determined by dot blot hybridization. By this
      approach, nine genetic regions were found to be significantly more prevalent in
      otitis media strains. Classification tree analysis of lic2B, hmwA, and the nine
      new potential otitis media virulence genes revealed two H. influenzae pathotypes
      associated with otitis media.

PMID- 17005746
TI  - Characteristics of Staphylococcus aureus strains isolated in Poland in 1996 to
      2004 that were deficient in species-specific proteins.
AB  - One hundred seventy Staphylococcus aureus isolates, collected in 1996 to 2004,
      were reidentified by phenotypic and genotypic methods. One hundred ten of these
      (65%) were confirmed, as previously denoted, to be clumping factor (CF)- or free
      coagulase-deficient S. aureus, based on their phenotype. Based on the CF or
      coagulase production, three groups of phenotypically deficient S. aureus isolates
      were distinguished. Group 1 encompassed CF-positive and coagulase-deficient
      isolates, group 2 consisted of CF-deficient and coagulase-positive isolates, and
      group 3 included isolates that were CF positive, had delayed coagulase activity,
      and were deficient in other species-specific features. All investigated strains
      harbored the clfA, clfB, coa, spa, and nuc genes, but the presence of their
      products was not detected by the phenotypic methods. Glycopeptide susceptibility
      testing showed that 26 isolates (23.6%) were hetero-glycopeptide-intermediate S.
      aureus(hGISA) or hetero-teicoplanin-intermediate S. aureus (hTISA), based on the
      population analysis profile. The relatedness of the isolates was evaluated by
      multiple-locus variable number of tandem repeats analysis, pulsed-field gel
      electrophoresis (PFGE), and multilocus sequence typing. The phenotypically
      deficient S. aureus isolates were classified into PFGE types B (ST239-III) and D
      (ST246-IA) and were related to the common clones, Hungarian and Iberian,
      respectively, which have been widely disseminated in Poland and globally. The
      simultaneous occurrence of hGISA/hTISA and the CF-deficient phenotypes was found
      for 62.1% of isolates belonging to group 2. The majority of these isolates were
      assigned to the Iberian clone (PFGE type D; ST247-IA). An association between the
      defect in coagulase and that in thermonuclease production was observed, which
      concerned 59.2% of isolates of group 1. The majority of these isolates belonged
      to the Hungarian clone (PFGE type B; ST239-III).

PMID- 17005747
TI  - Influence of disk separation distance on accuracy of the disk approximation test
      for detection of inducible clindamycin resistance in Staphylococcus spp.
AB  - We undertook this study to assess the accuracy of the clindamycin-erythromycin
      disk approximation test (D-test) for detection of inducible clindamycin
      resistance in Staphylococcus spp. One hundred sixty-three Staphylococcus aureus
      and 68 coagulase-negative Staphylococcus (CoNS) spp. which were erythromycin
      nonsusceptible but clindamycin susceptible were tested using the D-test performed
      at both 15-mm and 22-mm disk separations and compared with genotyping as the
      "gold standard." The rate of inducible clindamycin resistance was 96.3% for S.
      aureus and 33.8% for CoNS spp. The sensitivities of the D-tests performed at 15
      mm and 22 mm were 100% and 87.7%, respectively, and specificities were 100% for
      both. The use of 22-mm disk separation for the D-test to detect inducible
      clindamycin resistance results in an unacceptably high very major error rate
      (12.3%). All isolates with false-negative results harbored the ermA gene, and the
      majority were methicillin-resistant Staphylococcus aureus. False-negative results
      were associated with smaller clindamycin zone sizes and double-edged zones. We
      recommend using a disk separation distance of </=15 mm. There is wide geographic
      variation in the rates of inducible clindamycin resistance, and each laboratory
      should determine the local rate before deciding whether to either perform the D
      test routinely or else report that all erythromycin-resistant S. aureus isolates
      are also clindamycin resistant.

PMID- 17005748
TI  - Molecular epidemiology of hospital-acquired vancomycin-resistant enterococci.
AB  - Vancomycin-resistant Enterococcus faecium strains are a significant cause of
      nosocomial infections in predisposed patients. Multiple-locus variable-number
      tandem repeat analysis (MLVA) has been validated recently by use of a global
      strain collection. In this report, we applied MLVA together with multilocus
      sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) to type 14
      isolates from three clusters of patients colonized or infected with vancomycin
      resistant Enterococcus faecium and another 10 epidemiologically unrelated
      isolates from the same hospital. The clusters could be distinguished by all three
      typing methods, which proved to be concordant. PFGE patterns provided the highest
      resolution. We observed seven sequence types (ST), six MLVA types (MT), and nine
      distinct ST/MT combinations. The combination of MLST and MLVA may be an
      alternative to PFGE in hospital epidemiology, providing the benefits of high
      accuracy, reproducibility, and portability.

PMID- 17005749
TI  - Identification of a Streptococcus agalactiae serotype III subtype 4 clone in
      association with adult invasive disease in Hong Kong.
AB  - Characterization of Streptococcus agalactiae serotype III isolates revealed a
      subtype 4 clone that has an indistinguishable pulsed-field gel electrophoresis
      pattern and possesses a C-alpha protein, IS1381, and a novel sequence type (ST),
      ST 283, by multilocus sequence tagging. This clone was significantly associated
      with diseases caused by invasive strains from nonpregnant adults (P <or= 0.01,
      chi-square test) and was not present in the genital tracts of pregnant mothers.

PMID- 17005750
TI  - Multicenter performance evaluation of a new TaqMan PCR assay for monitoring human
      immunodeficiency virus RNA load.
AB  - A TaqMan real-time PCR assay, the COBAS TaqMan human immunodeficiency virus (HIV)
      (HPS-CTMHIV) PCR assay, recently developed for the quantification of HIV type 1
      RNA in plasma, was evaluated in comparison with the licensed COBAS AMPLICOR HIV-1
      MONITOR (CAHIM) assay. In this study, we have analyzed the tests' sensitivities,
      precisions, and linearities using multiple replicates of a standard panel of HIV
      RNA covering a 7-logarithm range of concentrations, as well as serial threefold
      dilutions of high-titer clinical samples. The subtype inclusivity was also
      investigated, using a panel of subtypes A to H, while a collection of 160
      clinical samples was analyzed to assess the tests' specificities and the systems'
      similarities. The results of these experiments showed that the HPS-CTMHIV assay
      has a sensitivity of 53 copies/ml (95% hit rate), 100% specificity, and good
      intra- and interassay precision. The results of the HPS-CTMHIV assay were linear
      in the 50- to 10(7)-copies/ml range, with a correlation coefficient (R) for
      expected versus observed results of 0.98. Compared to the CAHIM assay, the HPS
      CTMHIV assay showed a high correlation (R=0.99) across the dynamic range of RNA
      concentrations that, for the CAHIM assay, requires two different sample
      preparations. Equivalent performances were also observed for the two systems in
      the detection and quantification of HIV subtypes A to H. These data indicate that
      the HPS-CTMHIV assay may be one of the tests of choice for monitoring viral load
      throughout the course of HIV infection and during highly active antiretroviral
      therapy.

PMID- 17005751
TI  - Listeria monocytogenes subgroups IIIA, IIIB, and IIIC delineate genetically
      distinct populations with varied pathogenic potential.
AB  - Listeria monocytogenes lineage III strains belonging to subgroups IIIA (n = 8),
      IIIB (n = 5), and IIIC (n = 6) were examined along with other known serotype
      strains (n = 11) by PCR and Southern hybridization using several recently
      described species-, virulence-, and serotype-specific primers and probes. The
      virulence of seven representative lineage III strains was then evaluated in mice
      via the intraperitoneal route. The results suggest that subgroup IIIA consists of
      typical rhamnose-positive avirulent serotype 4a and virulent serotype 4c strains,
      subgroup IIIC consists of atypical rhamnose-negative virulent serotype 4c
      strains, and subgroup IIIB consists of atypical rhamnose-negative virulent non
      serotype 4a and non-serotype 4c strains, some of which may be related to serotype
      7. It is possible that subgroup IIIB (including serotype 7) may represent a novel
      subspecies within L. monocytogenes.

PMID- 17005752
TI  - Two-center collaborative evaluation of performance of the BD phoenix automated
      microbiology system for identification and antimicrobial susceptibility testing
      of gram-negative bacteria.
AB  - The performance of the BD Phoenix Automated Microbiology System (BD Diagnostic
      Systems, Sparks, MD) was assessed for identification (ID) and antimicrobial
      susceptibility testing (AST) of the majority of clinically encountered bacterial
      isolates in a European collaborative two-center trial. A total of 494 bacterial
      isolates including various species of the Enterobacteriaceae and 110
      nonfermentative gram-negative bacteria were investigated: of these, 385 were
      single patient isolates, and 109 were challenge strains tested at one center. The
      performance of the Phoenix extended-spectrum beta-lactamase (ESBL) test was also
      evaluated for 203 strains of Escherichia coli, Klebsiella pneumoniae, and
      Klebsiella oxytoca included in the study. Forty-two antimicrobial drugs were
      tested, including members of the following drug classes: aminoglycosides, beta
      lactam antibiotics, beta-lactam/beta-lactamase inhibitors, carbapenems, cephems,
      monobactams, folate antagonists, quinolones, and others. Phoenix system ID
      results were compared to those of the laboratories' routine ID systems (API 20E
      and API CHE, ATB ID32E, ID32GN, and VITEK 2 [bioMerieux, Marcy l'Etoile,
      France]); Phoenix AST results were compared to those of frozen standard broth
      microdilution (SBM) panels according to NCCLS (now CLSI) guidelines (NCCLS
      document M100-S9, approved standard M7-A4). Discrepant results were repeated in
      duplicate. Concordant IDs of 98.4 and 99.1% were observed for the
      Enterobacteriaceae and the nonfermentative group, respectively. For AST results,
      the overall essential agreement was 94.2%; the category agreement was 97.3%; and
      the very major error rate, major error rate, and minor error rate were 1.6, 0.6,
      and 1.9%, respectively. In terms of ESBL detection, Phoenix results were 98.5%
      concordant with those of the reference system, with 98.0% sensitivity and 98.7%
      specificity. In conclusion, the Phoenix ID results showed high agreement with
      results of the systems to which they were being compared: the AST performance was
      highly equivalent to that of the SBM reference method, and the system proved to
      be very accurate for the detection of ESBL producers.

PMID- 17005753
TI  - First case of bacteremia and multifocal cellulitis due to Helicobacter canis in
      an immunocompetent patient.
AB  - Bacteremia due to Helicobacter canis has been reported in a patient with X-linked
      hypogammaglobulinemia. Here we report on the first human case of H. canis
      bacteremia in an immunocompetent host. Identification of the organism was made by
      genetic and phylogenetic analyses of the complete 16S rRNA sequence.

PMID- 17005754
TI  - Phaeoacremonium krajdenii, a cause of white grain eumycetoma.
AB  - We describe the first case of white grain pedal eumycetoma caused by
      Phaeoacremonium krajdenii in a 41-year-old man from Goa, India. Based on
      histological examination of biopsy tissue showing serpentine granules, a culture
      of the granules yielding phaeoid fungal colonies, and morphological
      characteristics and sequence comparison of the partial beta-tubulin gene with the
      ex-type isolate of P. krajdenii, the causal agent was identified as P. krajdenii.

PMID- 17005755
TI  - Specific primers for rapid detection of Microsporum audouinii by PCR in clinical
      samples.
AB  - This report describes application of PCR fingerprinting to identify common
      species of dermatophytes using the microsatellite primers M13, (GACA)4, and
      (GTG)5. The initial PCR analysis rendered a specific DNA fragment for Microsporum
      audouinii, which was cloned and sequenced. Based on the sequencing data of this
      fragment, forward (MA_1F) and reverse (MA_1R) primers were designed and verified
      by PCR to establish their reliability in the diagnosis of M. audouinii. These
      primers produced a singular PCR band of 431 bp specific only to strains and
      isolates of M. audouinii, based on a global test of 182 strains/isolates
      belonging to 11 species of dermatophytes. These findings indicate these primers
      are reliable for diagnostic purposes, and we recommend their use in laboratory
      analysis.

PMID- 17005756
TI  - Integrons containing the VIM-2 metallo-beta-lactamase gene among imipenem
      resistant Pseudomonas aeruginosa strains from different Chinese hospitals.
AB  - A total of 140 nonrepetitive strains of imipenem-resistant Pseudomonas aeruginosa
      were isolated from five different Chinese hospitals. Fourteen isolates were
      confirmed to contain the VIM-2 metallo-beta-lactamase gene. Twelve isolates
      harbored two kinds of class 1 integron, containing both VIM-2- and aminoglycoside
      resistant genes.

PMID- 17005757
TI  - MultiCode-RTx real-time PCR system for detection of subpopulations of K65R human
      immunodeficiency virus type 1 reverse transcriptase mutant viruses in clinical
      samples.
AB  - We report a real-time PCR assay capable of detecting drug-resistant human
      immunodeficiency virus type 1 reverse transcriptase K65R mutant virus at a level
      of 0.5% in polymorphic patient plasma specimens. Fifty-three treatment-naive and
      20 treatment-experienced specimens were successfully genotyped with the new
      method. Results were in agreement with population sequencing and the labor
      intensive single-genome sequencing method.

PMID- 17005758
TI  - Limitations of DNA sequencing for diagnosis of a mixed infection by two fungi,
      Phaeoacremonium venezuelense and a Plectophomella sp., in a transplant recipient.
AB  - We describe a rare case of a subcutaneous infection by both Phaeoacremonium
      venezuelense and Plectophomella sp. in a Brazilian male. Sequencing of a beta
      tubulin gene fragment allowed us to confirm the identification of the former.
      However, a similar procedure of sequencing rRNA gene fragments was not useful for
      the identification of the latter fungus.

PMID- 17005759
TI  - Proposal for standardization of optimized mycobacterial interspersed repetitive
      unit-variable-number tandem repeat typing of Mycobacterium tuberculosis.
AB  - Molecular typing based on 12 loci containing variable numbers of tandem repeats
      of mycobacterial interspersed repetitive units (MIRU-VNTRs) has been adopted in
      combination with spoligotyping as the basis for large-scale, high-throughput
      genotyping of Mycobacterium tuberculosis. However, even the combination of these
      two methods is still less discriminatory than IS6110 fingerprinting. Here, we
      define an optimized set of MIRU-VNTR loci with a significantly higher
      discriminatory power. The resolution and the stability/robustness of 29 loci were
      analyzed, using a total of 824 tubercle bacillus isolates, including
      representatives of the main lineages identified worldwide so far. Five loci were
      excluded for lack of robustness and/or stability in serial isolates or isolates
      from epidemiologically linked patients. The use of the 24 remaining loci
      increased the number of types by 40%--and by 23% in combination with
      spoligotyping--among isolates from cosmopolitan origins, compared to those
      obtained with the original set of 12 loci. Consequently, the clustering rate was
      decreased by fourfold--by threefold in combination with spoligotyping--under the
      same conditions. A discriminatory subset of 15 loci with the highest evolutionary
      rates was then defined that concentrated 96% of the total resolution obtained
      with the full 24-locus set. Its predictive value for evaluating M. tuberculosis
      transmission was found to be equal to that of IS6110 restriction fragment length
      polymorphism typing, as shown in a companion population-based study. This 15
      locus system is therefore proposed as the new standard for routine
      epidemiological discrimination of M. tuberculosis isolates and the 24-locus
      system as a high-resolution tool for phylogenetic studies.

PMID- 17005760
TI  - Simultaneous amplification and identification of 25 human papillomavirus types
      with Templex technology.
AB  - The majority of existing human papillomavirus (HPV) genotyping assays are based
      on multiplex PCR using consensus or degenerate primers. We developed a Templex
      HPV assay that simultaneously detects and identifies 25 common HPV genotypes in a
      single-tube reaction using type-specific primers for the HPV-specific E6 and E7
      genes. The analytical sensitivities of the Templex assay for HPV type 16 (HPV
      16), -18, and -56 were 20, 100, and 20 copies per reaction mixture, respectively.
      The Templex assay provides semiquantitative information on each type when
      multiple HPV types coexist in one reaction. We tested 109 clinical cervical
      specimens previously evaluated with the Digene HC2 high-risk HPV DNA test and
      found 95.4% concordance between the assay results. The Templex assay provided
      type-specific results and found multiple types in 29.2% (14 of 48) of high-risk
      HPV-positive samples. The entire Templex procedure, including DNA extraction, can
      be completed within 5 hours, providing a rapid and reliable diagnostic tool for
      HPV detection and typing that is amenable to automation.

PMID- 17005761
TI  - Risk of oesophageal cancer by histology among patients hospitalised for
      gastroduodenal ulcers.
AB  - OBJECTIVE: The mechanism behind the epidemiologically evident inverse relation
      between Helicobacter pylori seropositivity and risk of oesophageal adenocarcinoma
      (OAC) remains obscure. Severe corpus gastritis is unlikely to be in the causal
      pathway. With the hypothesis of a uniformly low risk, the associations of OAC
      with duodenal ulcer and gastric ulcer were explored, both linked to H pylori
      infection but with different patterns of bacterial colonisation and intragastric
      acidity. Possible associations of oesophageal squamous cell carcinoma (OSCC) with
      these ulcer types were also addressed. DESIGN AND PATIENTS: Retrospective cohorts
      of 61,548 and 81,379 unoperated patients with duodenal ulcer and gastric ulcer,
      respectively, recorded in the Swedish Inpatient Register since 1965, were
      followed from the first hospitalisation until the date of any cancer, death,
      emigration, definitive surgery, or 31 December 2003. Standardised incidence
      ratios (SIRs), with 95% CIs, expressed relative risk of oesophageal cancer,
      compared with the Swedish population matched for age, sex and calendar period.
      RESULTS: Contrary to expectation, patients with duodenal ulcer had a significant
      70% excess risk of OAC (SIR 1.7, 95% CI 1.1 to 2.5). Gastric ulcer was unrelated
      to OAC (SIR 1.1, 95% CI 0.6 to 1.7). Although duodenal ulcer was non
      significantly associated with a small excess of OSCC (SIR 1.3, 95% CI 0.96 to
      1.8), gastric ulcer was linked to 80% increased risk (SIR 1.8, 95% CI 1.4 to
      2.3). CONCLUSION: The inverse association between H pylori and OAC does not
      pertain to all infections. The pattern of gastric colonisation and/or impact on
      acidity may be important. With the reservation for the possibility of
      confounding, this study also provides some support for the importance of
      intragastric environment in the aetiology of OSCC.

PMID- 17005762
TI  - Liver fibrosis in women with chronic hepatitis C: evidence for the negative role
      of the menopause and steatosis and the potential benefit of hormone replacement
      therapy.
AB  - BACKGROUND AND AIMS: The rates of fibrosis progression in chronic hepatitis C are
      significantly different between males and females. The antifibrogenic effect of
      oestrogen has been proposed, possibly via inhibition of stellate cells. The aim
      of this study was to evaluate the severity of chronic hepatitis C in women, in
      relation to the menopause, steatosis and hormone replacement therapy (HRT).
      METHODS: From November 2003 to October 2004, women with chronic hepatitis C were
      enrolled prospectively. A questionnaire was completed prospectively and a blood
      sample was obtained on the day of biopsy. We identified characteristics
      associated with moderate/severe fibrosis using univariate and multivariate
      analysis. RESULTS: 251 women were included in the study. 122 women (52%) were
      menopausal and 65 were receiving HRT. 61 (24%) women with moderate/severe
      fibrosis (F2-F4, Metavir score) had a longer known duration of infection (>15
      years), a higher body mass index and presented with steatosis more frequently
      than 190 (76%) women with mild fibrosis (F0-F1). Women with F2-F4 were more often
      menopausal (67% v 47%). The probability of fibrosis F2-F4 was lower for
      menopausal women receiving HRT (p = 0.012). Steatosis was more frequent and more
      severe in menopausal women. CONCLUSIONS: Severity of fibrosis was associated with
      a longer duration of infection (>15 years), a higher body mass index, advanced
      steatosis and the menopause. Menopausal women receiving HRT presented with a
      lower stage fibrosis. These results reinforce the hypothesis of a protective role
      of oestrogens in the progression of fibrosis. Steatosis may be implicated in the
      progression of fibrosis after the menopause.

PMID- 17005763
TI  - Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in
      the jejunum.
AB  - BACKGROUND: Increased numbers of mast cells and mast cell activation in distal
      gut segments are associated with symptom onset and severity in irritable bowel
      syndrome (IBS). Although upper gut symptoms are common, mast cells have not been
      thoroughly evaluated in proximal gut in IBS patients. METHODS: Jejunal biopsies
      obtained by Watson's capsule, aspiration of intestinal fluid and one blood sample
      were obtained in 20 diarrhoea-predominant patients with IBS (D-IBS) and 14
      healthy volunteers (H). Psychological stress (Holmes-Rahe Scale) and depression
      (Beck's Depression Inventory) were evaluated at baseline and food and respiratory
      allergy excluded. Biopsies were processed for H&E staining and microscopic
      inflammation assessed by counting intraepithelial lymphocytes. Mast cells in
      lamina propria were counted by immunohistochemistry with CD117 (c-kit). Tryptase
      concentration was measured in intestinal fluid and serum. RESULTS: D-IBS patients
      showed higher psychological stress than healthy volunteers (D-IBS: 203 (SD 114) v
      H: 112 (SD 99); p = 0.019). Immunohistochemical staining of jejunal mucosa
      revealed mild increase in intraepithelial CD3+ cells in D-IBS patients (D-IBS:
      15.3 (SD 5.5; 95% CI 12.7 to 17.9) v H: 10.3 (SD 3.9; 95% CI 8.0 to 12.5); p =
      0.006). Moreover, D-IBS patients showed marked increase in mast cells numbers (D
      IBS: 34 (SD 9.3); H: 15.3 (SD 4.4) mast cells/hpf; p<0.001) and higher tryptase
      concentration in jejunal fluid (D-IBS: 0.45 (SD 0.38); H: 0.09 (SD 0.10)
      microg/l; p = 0.005). Upper gut symptoms were not associated with gender, mast
      cell counts, jejunal tryptase or basal stress. CONCLUSION: This jejunal mucosal
      inflammatory profile may help identify diarrhoea-predominant IBS, a stress
      related disorder.

PMID- 17005764
TI  - Rate and predictors of treatment prescription for hepatitis C.
AB  - BACKGROUND: The true treatment rate for hepatitis C virus (HCV) in veterans is
      unknown. AIM: To determine the treatment prescription rates and predictors of
      treatment prescription for HCV in a large national population. METHODS: The
      Department of Veterans Affairs National Patient Care Database (NPCD) was used to
      identify all HCV-infected people between the fiscal years 1999 and 2003 using the
      International classification of diseases, 9th revision codes. Demographic
      information, medical and psychiatric comorbidities, and drug and alcohol use
      diagnoses were retrieved. Pharmacy data were retrieved from the Department of
      Veterans Affairs Pharmacy Benefits Management (PBM) database. Logistic regression
      analysis was used to determine the predictors of treatment for HCV in HCV.
      RESULTS: 113 927 veterans in the Department of Veterans Affairs care with a
      diagnosis of HCV were identified. The treatment prescription rate for HCV was
      11.8%. Patients not prescribed treatment were older, more likely to be from
      minority races, have more alcohol and drug misuse, and have medical and
      psychiatric comorbid conditions. In a multivariate logistic regression model, the
      following factors were predictive of non-treatment for HCV: increasing age (odds
      ratio (OR) 0.77 for each 5-year increase in age; 95% confidence interval (CI)
      0.76 to 0.78); black race (OR 0.64; 95% CI 0.6 to 0.68); Hispanic race (OR 0.88;
      95% CI 0.8 to 0.96); alcohol abuse and dependence (OR 0.62; 95% CI 0.59 to 0.65);
      drug abuse and dependence (OR 0.78; 95% CI 0.74 to 0.82); anaemia (OR 0.18; 95%
      CI 0.16 to 0.21); hepatitis B infection (OR 0.72; 95% CI 0.62 to 0.83); coronary
      artery disease (OR 0.9; 95% CI 0.85 to 0.97); stroke (OR 0.75; 95% CI 0.67 to
      0.85); bipolar disorder (OR 0.64; 95% CI 0.58 to 0.70); major depression (OR
      0.72; 95% CI 0.67 to 0.77); mild depression (OR 0.56; 95% CI 0.53 to 0.59); and
      schizophrenia (OR 0.71; 95% CI 0.65 to 0.77). The following factors were
      associated with a higher likelihood of treatment prescription for HCV: liver
      cirrhosis (OR 1.6; 95% CI 1.5 to 1.7); and diabetes (OR 1.07; 95% CI 1.02 to
      1.12). CONCLUSIONS: A small number of HCV-infected veterans were prescribed
      treatment for HCV. Non-treatment is associated with increasing age, non-white
      race, drug and alcohol abuse, and dependence and comorbid illnesses. Reasons for
      non-treatment need further study.

PMID- 17005765
TI  - Long-term effect of Helicobacter pylori eradication on plasma homocysteine in
      elderly patients with cobalamin deficiency.
AB  - BACKGROUND: Helicobacter pylori gastritis may lead to impairment of the
      production of pepsinogen and acid, which are essential to cobalamin absorption.
      In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for
      cardio and cerebrovascular diseases. AIM: To evaluate the effect of H pylori
      eradication on plasma homocysteine levels in elderly patients. PATIENTS: Sixty
      two H pylori-positive elderly patients with cobalamin deficiency were
      prospectively studied. METHODS: Homocysteine and cobalamin concentrations were
      determined before, 6 and 12 months after H pylori eradication. RESULTS: Corpus
      atrophy was observed in a few patients; otherwise, in most of them, the degree of
      corpus gastritis was moderate to severe. The initial homocysteine mean (SD)
      levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow
      up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication
      (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7)
      pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after
      treatment, respectively (p<0.001 for both). Although the erythrocyte mean
      corpuscular volume was within reference intervals, it decreased significantly 6
      (p = 0.002) and 12 (p<0.001) months after treatment. CONCLUSIONS: The results of
      the current study demonstrated that the eradication of H pylori in elderly
      patients with cobalamin deficiency is followed by increasing of cobalamin and
      decreasing of homocysteine blood levels.

PMID- 17005766
TI  - A prospective comparative study of narrow-band imaging, chromoendoscopy, and
      conventional colonoscopy in the diagnosis of colorectal neoplasia.
AB  - BACKGROUND: Discrimination between neoplastic and non-neoplastic lesions is
      crucial in colorectal cancer screening. Application of narrow-band imaging (NBI)
      in colonoscopy visualises mucosal vascular networks in neoplastic lesions and may
      improve diagnostic accuracy. AIM: To compare the diagnostic efficacy of NBI in
      differentiating neoplastic from non-neoplastic colorectal lesions with diagnostic
      efficacies of standard modalities, conventional colonoscopy, and chromoendoscopy.
      METHODS: In this prospective study, 180 colorectal lesions from 133 patients were
      observed with conventional colonoscopy, and under low-magnification and high
      magnification NBI and chromoendoscopy. Lesions were resected for
      histopathological analysis. Endoscopic images were stored electronically and
      randomly allocated to two readers for evaluation. Sensitivity, specificity and
      diagnostic accuracy of each endoscopic modality were assessed by reference to
      histopathology. RESULTS: NBI and chromoendoscopy scored better under high
      magnification than under low magnification in comparison with conventional
      colonoscopy. The diagnostic accuracy of NBI with low or high magnification was
      significantly higher than that of conventional colonoscopy (low magnification: p
      = 0.0434 for reader 1 and p = 0.004 for reader 2; high magnification: p<0.001 for
      both readers) and was comparable to that of chromoendoscopy. CONCLUSION: Both low
      magnification and high-magnification NBI were capable of distinguishing
      neoplastic from non-neoplastic colorectal lesions; the diagnostic accuracy of NBI
      was better than that of conventional colonoscopy and equivalent to that of
      chromoendoscopy. The role of NBI in screening colonoscopy needs further
      evaluation.

PMID- 17005767
TI  - Prospective comparison of secretin-stimulated magnetic resonance
      cholangiopancreatography with manometry in the diagnosis of sphincter of Oddi
      dysfunction types II and III.
AB  - BACKGROUND: In sphincter of Oddi dysfunction (SOD), sphincter of Oddi manometry
      (SOM) predicts the response to sphincterotomy, but is invasive and associated
      with complications. AIM: To evaluate the role of secretin-stimulated magnetic
      resonance cholangiopancreatography (ss-MRCP) in predicting the results of SOM in
      patients with suspected type II or III SOD. METHODS: MRCP was performed at
      baseline and at 1, 3, 5 and 7 min after intravenous secretin. SOD was diagnosed
      when the mean basal sphincter pressure at SOM was >40 mm Hg. Long-term outcome
      after SOM, with or without endoscopic sphincterotomy, was assessed using an 11
      point (0-10) Likert scale. RESULTS: Of 47 patients (male/female 9/38; mean age 46
      years; range 27-69 years) referred for SOM, 27 (57%) had SOD and underwent
      biliary and/or pancreatic sphincterotomy. ss-MRCP was abnormal in 10/16 (63%)
      type II and 0/11 type III SOD cases. The diagnostic accuracy of ss-MRCP for SOD
      types II and III was 73% and 46%, respectively. During a mean follow-up of 31.6
      (range 17-44) months, patients with normal SOM and SOD type II experienced a
      significant reduction in symptoms (mean Likert score 8 vs 4; p = 0.03, and 9 vs
      1.6; p = 0.0002, respectively), whereas in patients with SOD type III, there was
      no improvement in pain scores. All patients with SOD and an abnormal ss-MRCP (n =
      12) reported long-term symptom improvement (mean Likert score 9.2 v 1.2,
      p<0.001). CONCLUSIONS: ss-MRCP is insensitive in predicting abnormal manometry in
      patients with suspected type III SOD, but is useful in selecting patients with
      suspected SOD II who are most likely to benefit from endotherapy.

PMID- 17005768
TI  - Detection of vascular expression of E-selectin in vivo with MR imaging.
AB  - PURPOSE: To develop a contrast agent for targeting E-selectin expressed on
      activated vascular endothelium and to evaluate detection of the agent with
      magnetic resonance (MR) imaging in an in vivo mouse model of inflammation.
      MATERIALS AND METHODS: All animal experiments were approved according to animal
      welfare and local ethics committee regulations. An anti-murine E-selectin F(ab')2
      monoclonal antibody, MES-1, was conjugated with ultrasmall superparamagnetic iron
      oxide (USPIO) nanoparticles. Flow cytometry, Perl Prussian blue staining for
      iron, and MR imaging were performed by using Chinese hamster ovary (CHO) cells
      expressing mouse E-selectin to detect binding of the conjugate in vitro, and a
      mouse model of contact hypersensitivity to oxazolone in the ear was used to
      investigate the in vivo characteristics of the MES-1-USPIO. Serial imaging was
      performed by using a 9.4-T MR imaging system with a custom receive-only coil.
      Tissue slices were stained to define distribution of E-selectin expression and
      localization of the MES-1-USPIO conjugate. RESULTS: MES-1-USPIO was shown to bind
      to CHO cells expressing mouse E-selectin in vitro. After injection of MES-1-USPIO
      in vivo, distinct changes in R2 relaxation rate (1/T2) characteristics were
      detected in inflamed ears when they were compared with control ears. Histologic
      analysis confirmed the vascular endothelial distribution of MES-1-USPIO.
      CONCLUSION: E-selectin expression in vivo can be selectively and directly imaged
      noninvasively with MR. This has the potential to be useful in the study of
      inflammatory disease.

PMID- 17005769
TI  - Interobserver agreement for Letournel acetabular fracture classification with
      multidetector CT: are standard Judet radiographs necessary?
AB  - PURPOSE: To retrospectively evaluate interobserver agreement for Letournel
      acetabular fracture classification with radiography alone and multidetector
      computed tomography (CT) alone and to retrospectively assess whether standard
      Judet views lead to a change in the classification. MATERIALS AND METHODS:
      Institutional review board approval was obtained; informed consent was not
      required for this HIPAA-compliant study, which included 101 imaging studies
      performed in 99 patients (78 male, 21 female; mean age, 43 years; age range, 15
      86 years) with acetabular fractures. Two musculoskeletal radiologists
      independently classified the fractures with radiography alone and multidetector
      CT alone. Multiplanar reformatted and three-dimensional (3D) CT images were
      reviewed at a computer workstation. Readers were shown radiographs at the end of
      multidetector CT image reading to see if this would change the multidetector CT
      based classification. kappa Values were calculated to assess interobserver
      agreement. For surgically treated patients, the McNemar test was used to compare
      the accuracy of readers' classifications. The reference standard was a
      combination of preoperative radiographic and multidetector CT image findings and
      intraoperative findings. RESULTS: Interobserver agreement was moderate (kappa =
      0.42) with radiography and substantial (kappa = 0.70) with multidetector CT.
      Multidetector CT classification was changed in two cases (one case for each
      reader) after standard Judet views were added. In 73 surgically treated patients,
      agreement with the surgeons' classification was higher with multidetector CT than
      with radiography (P < .01 for one reader, P = .06 for the other reader).
      CONCLUSION: There is substantial interobserver agreement for Letournel acetabular
      fracture classification with multiplanar reformatted and 3D multidetector CT
      images. Standard Judet pelvic radiographs add little information for changing the
      multidetector CT classification.

PMID- 17005770
TI  - Pleural mesothelioma: sensitivity and incidence of needle track seeding after
      image-guided biopsy versus surgical biopsy.
AB  - PURPOSE: To retrospectively compare the sensitivity of image-guided core-needle
      biopsy, thoracoscopy, and thoracotomy in the diagnosis of malignant pleural
      mesothelioma and to retrospectively determine the incidence of needle track
      seeding after these procedures. MATERIALS AND METHODS: Institutional review board
      approval was obtained, and informed consent was not required. The study included
      100 consecutive patients (81 men, 19 women; average age, 65.8 years) with
      pathologically proved malignant pleural mesothelioma who were treated between
      1994 and 2002. A total of 23 core-needle biopsies were performed in 22 patients,
      and 11 of these biopsies were coupled with fine-needle aspiration biopsy. A
      coaxial technique was used, and biopsy was performed with fluoroscopic (12
      biopsies), computed tomographic (10 biopsies), or ultrasonographic (one biopsy)
      guidance. Sixty-nine patients underwent surgical biopsy in the form of
      thoracoscopy (n = 51) and/or thoracotomy (n = 21). Patients were followed up
      clinically for any evidence of needle track seeding after image-guided or
      surgical procedures. The sensitivity of diagnostic procedures and the incidence
      of needle track seeding as a result of intervention were calculated. RESULTS:
      Sensitivity was 86% for image-guided core-needle biopsy, 94% for thoracoscopy,
      and 100% for thoracotomy. The incidence of needle track seeding was 4% for image
      guided core-needle biopsy and 22% for surgical biopsy. CONCLUSION: Image-guided
      core-needle biopsy in patients with malignant pleural mesothelioma has a lower
      incidence of needle track seeding than surgical biopsy and has a high sensitivity
      for diagnosis.

PMID- 17005771
TI  - Distribution of stage I lung cancer growth rates determined with serial
      volumetric CT measurements.
AB  - PURPOSE: To retrospectively determine the distribution of stage I lung cancer
      growth rates with serial volumetric computed tomographic (CT) measurements.
      MATERIALS AND METHODS: This study was institutional review board approved and
      HIPAA compliant. The informed consent requirement was waived. Patients (n = 149)
      with stage I lung cancer who underwent two pretreatment CT examinations 25 or
      more days apart were identified. At the first and last examinations, tumor
      perimeters were manually inscribed by using software tools and the cross
      sectional area was calculated. To calculate tumor volume, the summed areas were
      multiplied by the section increment and a formula was applied to reduce partial
      volume effects. Doubling time (DT) was calculated by using the volume and
      interscanning interval. The percentages of tumors that would surpass volume
      increase thresholds of 5%-25% for detectable growth at different time intervals
      were calculated. Age at diagnosis was compared with the reciprocal of DT, time
      interval between CT examinations, and initial tumor volume by using Pearson
      correlation. P < .05 denoted statistical significance. RESULTS: Lung cancer was
      stage IA in 99 patients and stage IB in 50. Median patient age was 72 years, and
      median interscanning interval was 130 days. Median tumor volumes were 3000 and
      6213 mm3 at the first and last examinations, respectively. Median DT was 207
      days; 21 tumors did not increase in volume between examinations. The
      interscanning interval required for 90% of growing tumors to surpass the growth
      threshold ranged from 8 weeks (5% threshold) to 37 weeks (25% threshold). Fifty
      three percent of growing tumors would surpass the 25% threshold at 8 weeks, and
      95% would surpass it at 1 year. Age at diagnosis was negatively correlated with
      growth rate (P = .047); there was no correlation between growth rate and either
      age at diagnosis or interscanning interval. CONCLUSION: At serial volumetric CT
      measurements, there was wide variability in growth rates. Some biopsy-proved
      cancers decreased in volume between examinations.

PMID- 17005772
TI  - Diaphragmatic weakness after transcatheter arterial chemoembolization of inferior
      phrenic artery for treatment of hepatocellular carcinoma.
AB  - PURPOSE: To prospectively assess the diaphragmatic anatomic and functional
      consequences of transcatheter arterial chemoembolization (TACE) of the inferior
      phrenic artery in patients with hepatocellular carcinoma. MATERIALS AND METHODS:
      Informed consent and institutional review board approval were obtained. Fifteen
      patients (13 men, two women; mean age, 52 years; age range, 22-61 years) who
      underwent TACE of the inferior phrenic artery for treatment of hepatocellular
      carcinoma were enrolled. The right inferior phrenic artery was embolized in 14
      patients, and the left inferior phrenic artery was embolized in one patient.
      Chest radiography, fluoroscopy, computed tomography (CT), and pulmonary function
      tests were performed before and after TACE of the inferior phrenic artery. The
      post-TACE examinations were performed 2-3 months after TACE, and the results were
      compared with those of the pre-TACE examinations. A paired t test or the Wilcoxon
      signed rank test was used for statistical analyses. RESULTS: At chest radiography
      and fluoroscopy, six of 15 patients (40%) had both elevation and movement
      abnormality of the ipsilateral hemidiaphragm after TACE of the inferior phrenic
      artery. The mean (+/- standard deviation) diaphragmatic thickness on CT scans
      changed from 9.11 mm +/- 3.02 to 7.67 mm +/- 2.27 after TACE (P = .048). The mean
      vital capacity also was significantly decreased after TACE, from 91.87% +/- 18.52
      to 82.27% +/- 16.94 of the predicted value (P = .006). The decreases in
      diaphragmatic thickness and vital capacity were most pronounced in the patients
      with abnormal findings at chest radiography and fluoroscopy. CONCLUSION: After
      TACE of the inferior phrenic artery, a substantial portion of patients showed
      functional and anatomic evidence of diaphragmatic weakness.

PMID- 17005773
TI  - CT colonography with computer-aided polyp detection: volume and attenuation
      thresholds to reduce false-positive findings owing to the ileocecal valve.
AB  - PURPOSE: To retrospectively identify volume and average attenuation thresholds
      for differentiating between ileocecal valve (ICV) and polyp at computed
      tomographic (CT) colonography with computer-aided detection (CAD). MATERIALS AND
      METHODS: Informed consent (with consent for future retrospective research) and
      institutional review board (IRB) approval were obtained for the original
      prospective study. This retrospective study had IRB approval, as well, and was
      HIPAA-compliant. A total of 496 patients were selected from a larger screening
      population. CT colonographic images from 394 patients (227 men, 167 women; mean
      age, 58.0 years; range, 40-79 years) were used as a training set, and images from
      102 patients (76 men, 26 women; mean age, 59.8 years; range, 46-79 years) were
      used as a test set. A series of 2742 volume and attenuation thresholds, for which
      segmented findings both larger in volume and lower in average attenuation were
      labeled as ICVs and remaining findings were labeled polyps, were applied to the
      training set to determine settings with 100% sensitivity for polyp detection and
      the highest specificity for ICV detection. The optimal settings were then applied
      to the test set. Significance was assessed with the Fisher exact test, and 95%
      confidence intervals (CIs) were computed for sensitivity and specificity.
      RESULTS: A total of 386 ICVs and 67 adenomatous polyps from the training set and
      102 ICVs and 138 adenomatous polyps from the test set could be segmented with a
      three-dimensional segmentation algorithm. When supine and prone images were
      counted individually, 746 nonunique ICVs from the training set and 191 from the
      test set were segmentable. In the training set, a volume of 600 mm(3) and an
      attenuation of 36 HU provided 100% sensitivity (67 polyps; 95% CI: 93%, 100%) and
      the optimal 83% specificity (618 of 746 ICVs; 95% CI: 80%, 85%). When applied to
      the test set, this combination provided 97% sensitivity (134 of 138 polyps; 95%
      CI: 92%, 99%) and 84% specificity (160 of 191 ICVs; 95% CI: 78%, 89%).
      Differences in sensitivity and specificity in the detection of polyps between the
      sets were not significant. CONCLUSION: Volume and average CT attenuation
      thresholds can help differentiate most ICVs from true polyps.

PMID- 17005774
TI  - Sympathetic skin response: monitoring of CT-guided lumbar sympathetic blocks.
AB  - PURPOSE: To prospectively evaluate accuracy of sympathetic skin response (SSR)
      for monitoring computed tomography (CT)-guided lumbar sympathetic blocks, with
      palpable temperature increase in the foot 30 minutes after injection serving as
      the reference standard. MATERIALS AND METHODS: Institutional review board
      approval and written informed consent were obtained. Seventy individual lumbar
      sympathetic blocks were performed in 13 patients (six female, seven male; mean
      age, 45 years) with reflex sympathetic dystrophy of the foot. A 22-gauge needle
      was advanced to the sympathetic trunk at midlumbar level with CT fluoroscopic
      guidance, and 1 mL of iopamidol (200 mg of iodine per milliliter) and 5 mL of
      0.5% bupivacaine were injected. SSR was monitored in both feet before and after
      bupivacaine injection. SSRs were activated with painless low-strength (5-20-mA)
      electrical stimuli. SSR ratio (SSR in the injected foot versus SSR in the
      contralateral foot) was calculated before injection and repeatedly at 1-minute
      intervals thereafter. Needle tip position and distribution of bupivacaine were
      measured on CT images. Receiver operating characteristic curves for SSR ratio
      were calculated until 7 minutes after injection. Logistic regression analyses
      adjusted for clustering were calculated for SSR ratio, injection parameters,
      needle tip position, and bupivacaine distribution. RESULTS: Thirty minutes after
      injection, 83% of procedures were considered clinically successful. An SSR cutoff
      ratio of 1:10 was used, and sensitivity, specificity, and accuracy of SSR for
      prediction of clinical success were 84%, 92%, and 86%, respectively, 4 minutes
      after injection and 95%, 92%, and 94%, respectively, 7 minutes after injection.
      Needle tip position (P = .19), medial and lateral borders of bupivacaine
      distribution (P = .11 and .056), and distance between bupivacaine distribution
      and the vertebral body (P = .41) were not significantly different between
      successful and unsuccessful injections. CONCLUSION: SSR can be used to correctly
      identify needle tip position in lumbar sympathetic blocks 6 and 7 minutes after
      injection.

PMID- 17005775
TI  - MR imaging with remote control: feasibility study in cardiovascular disease.
AB  - The institutional review board approved this HIPAA-compliant study and waived
      informed consent. The purpose was to retrospectively evaluate remote control
      magnetic resonance (MR) imaging in complex cardiovascular procedures, whereby
      operational expertise was made available locally from a remote location. Thirty
      patients underwent cardiac (12 patients) and/or vascular (30 patients) 1.5-T MR
      imaging with a remote operator by using a personal computer. All patient studies
      were compared with 30 control studies obtained with conventional local imaging.
      Cardiac cine, myocardial delayed enhancement, and MR angiograms were assessed for
      overall image quality and motion artifact. MR angiograms were evaluated for
      vascular definition. Image quality was excellent in 90% (38 of 42) of remote
      images versus 60% (25 of 42) of control group images (P < .01). Scores for motion
      artifact were not significantly different (P = .11). Interactive MR imaging was
      successfully implemented with remote control in complex cardiovascular cases;
      diagnostic quality of images was superior to that of images obtained locally.

PMID- 17005776
TI  - A review of an emerging enteric pathogen: enteroaggregative Escherichia coli.
AB  - Enteroaggregative Escherichia coli (EAEC) is an increasingly recognized enteric
      pathogen. It is a cause of both acute and persistent diarrhoea among children,
      adults and HIV-infected persons, in both developing and developed countries. In
      challenge studies, EAEC has caused diarrhoeal illness with the ingestion of
      10(10) c.f.u. Outbreaks of diarrhoeal illness due to EAEC have been reported, and
      linked to the ingestion of contaminated food. Diarrhoeal illness due to EAEC is
      the result of a complex pathogen-host interaction. Some infections due to EAEC
      result in diarrhoeal illness and elicit an inflammatory response, whereas other
      infections do not result in a symptomatic infection. Many putative virulence
      genes and EAEC strains that produce biofilm have been identified; however, the
      clinical significance of these genes and of biofilm production has yet to be
      defined. A -251 AA single nucleotide polymorphism (SNP) in the interleukin (IL)-8
      promoter region is reported to increase host susceptibility to EAEC diarrhoea.
      Ciprofloxacin and rifaximin continue to be an effective treatment in persons
      infected with EAEC. This review is intended to provide an updated review for
      healthcare workers on EAEC, an emerging enteric pathogen.

PMID- 17005777
TI  - Inhibition of swarming and virulence factor expression in Proteus mirabilis by
      resveratrol.
AB  - Resveratrol (3,5,4-trihydroxy-trans-stilbene) is a phytoalexin compound with anti
      inflammatory and antioxidant activities. The effect of resveratrol on swarming
      and virulence factor expression of Proteus mirabilis, an important pathogen
      infecting the urinary tract, was determined on swarming agar plates with and
      without the compound. Bacteria harvested at different times were assayed for cell
      length and the production of flagella, haemolysin and urease. Resveratrol
      inhibited P. mirabilis swarming and virulence factor expression in a dose
      dependent manner. Resveratrol significantly inhibited swarming at 15 microg ml(
      1), and completely inhibited swarming at 60 microg ml(-1). Inhibition of swarming
      and virulence factor expression was mediated through RsbA, a His-containing
      phosphotransmitter of the bacterial two-component signalling system possibly
      involved in quorum sensing. Complementation of an rsbA-defective mutant with the
      rsbA gene restored its responsiveness to resveratrol. The compound also inhibited
      the ability of P. mirabilis to invade human urothelial cells. These findings
      suggest that resveratrol has potential to be developed as an antimicrobial agent
      against P. mirabilis infection.

PMID- 17005778
TI  - Candida albicans HWP1 gene expression and host antibody responses in colonization
      and disease.
AB  - In vivo expression of the developmentally regulated Candida albicans hyphal wall
      protein 1 (HWP1) gene was analysed in human subjects who were culture positive
      for C. albicans and had oral symptoms (n=40) or were asymptomatic (n=29), or had
      vaginal symptoms (n=40) or were asymptomatic (n=29). HWP1 mRNA was present
      regardless of symptoms, implicating hyphal and possibly pseudohyphal forms in
      mucosal carriage as well as disease. As expected, in control subjects without
      oral symptoms (n=10) and without vaginal symptoms (n=10) who were culture
      negative in oral and vaginal samples, HWP1 mRNA was not detected. However,
      exposure to Hwp1 in healthy culture-negative controls, as well as in oral
      candidiasis and asymptomatic mucosal infections, was shown by the existence of
      local salivary and systemic adaptive antibody responses to Hwp1. The results are
      consistent with a role for Hwp1 in gastrointestinal colonization as well as in
      mucosal symptomatic and asymptomatic infections. Overall, Hwp1 and hyphal growth
      forms appear to be important factors in benign and invasive interactions of C.
      albicans with human hosts.

PMID- 17005779
TI  - IgG and IgG subclass antibodies in patients with active cutaneous leishmaniasis.
AB  - This research was planned to detect IgG and IgG subclasses in sera of patients
      with active cutaneous leishmaniasis (CL). Sera from 30 patients with active CL
      aged between 10 and 50 years and from 30 healthy controls aged between 8 and 50
      years were included in the study. Levels of IgG and its subclasses were measured
      by a nephelometer. Levels of IgG, IgG1 and IgG3 in the CL patients were higher
      than in the controls. In addition, IgG and IgG1, and IgG and IgG3 levels showed a
      significant positive correlation. These results showed that IgG subclasses could
      possibly be used as a helpful diagnostic marker in CL.

PMID- 17005780
TI  - Evaluation of antigenic variations between two virulent toxoplasma strains.
AB  - Toxoplasma gondii infection in humans is routinely assessed by serological means.
      Here, the authors attempted to compare the response of different Toxoplasma
      strains to serological tests and to evaluate the antigenic profiles of the RH and
      RH Ankara (TRH) strains with Western blotting. Anti-Toxoplasma IgG antibodies of
      72 patients were examined with the indirect immunofluorescence antibody (IFA)
      test, ELISA and Western blotting (WB) by using antigen from both strains.
      Antigenic variations between strains did not affect IFA and ELISA test results,
      but qualitative and quantitative differences between the WB patterns were
      observed. A number of bands with molecular masses varying between 17 and 105 kDa
      were detected in WB. Fourteen different bands were obtained with the assay
      performed with RH strain antigen. An additional four bands were observed with TRH
      strain antigen. Also, an 80 kDa band was observed to stain darker in the blot
      with TRH strain antigen, whereas with RH strain antigen 30 and 38 kDa bands were
      darker. The results showed that strain-specific polymorphism in tachyzoite
      antigens of different Toxoplasma strains is important in the evaluation of WB but
      not in conventional serological analyses such as ELISA and IFA.

PMID- 17005781
TI  - Detection of antibodies against Mycobacterium leprae culture filtrate protein-10
      in leprosy patients.
AB  - The prevalence of IgG antibodies against Mycobacterium leprae recombinant culture
      filtrate protein-10 (rCFP-10) was investigated in serum samples from 56 leprosy
      patients, 15 tuberculosis (TB) patients, 14 other skin-diseased patients and 20
      healthy subjects. On classifying the patients into bacterial index (BI)-positive
      and BI-negative groups, the assay showed 83.3 % (15/18) sensitivity for detection
      of BI-positive leprosy patients. On the other hand, the sensitivity for detection
      of BI-negative patients was 18.4 % (7/38). None of the 15 TB patients and 14
      other skin-diseased patients was positive; however, only one out of 20 healthy
      individuals was positive, indicating that antibody response to culture filtrate
      protein-10 (CFP-10) was highly specific (98.0 %; 48/49). Statistically, the
      performance of the CFP-10-based assay was found to be comparable (P>0.05) with
      that of an anti-phenolic glycolipid-I (PGL-I) antibody-detecting assay. Thus, M.
      leprae CFP-10 is potentially a specific antigen for measuring antibody response
      in BI-positive leprosy patients. Being a secreted antigen, CFP-10 may act as a
      marker for the viability of M. leprae inside the host, and hence its serological
      potential is worth exploring for application in monitoring the response of
      patients with BI-positive leprosy (a highly infectious form) during the course of
      chemotherapy. When comparing the bacteriological and serological results, an
      agreement of 82.1 % showed that seropositivity to M. leprae CFP-10 corresponded
      well with bacteriological criteria. Hence, CFP-10 seems to be a suitable antigen
      for classification of leprosy patients into BI-positive and BI-negative groups.

PMID- 17005782
TI  - Evaluation of a glycerol-preserved antigen in the direct agglutination test for
      diagnosis of visceral leishmaniasis at rural level in eastern Sudan.
AB  - Three-hundred and eight patients with suspected visceral leishmaniasis (VL) were
      received at Doka Hospital (eastern Sudan) during the period September 2004 to
      October 2005. The sensitivity and specificity of a glycerol-preserved (GP)
      antigen for VL diagnosis was assessed against the results of repeated lymph node
      aspiration and readings from a direct agglutination test (DAT) employing standard
      formaldehyde-fixed (FF) or freeze-dried (FD) antigen. Despite 13 months of
      storage at ambient temperature (28-47 degrees C), the GP antigen mean titres
      obtained from these 308 patients were no different from those that were FD
      (P=0.945) and stored under similar conditions, but were significantly different
      (P=0.019) from those that were FF and kept continuously at the optimum
      temperature for storage (4-8 degrees C). Taking the parasitological result as the
      gold standard and using a pre-established titre of 1 : 3200 as the DAT cut-off,
      the GP antigen revealed a sensitivity (91/105, 86.7 %) and specificity (187/203,
      92.1 %) comparable to that of FD antigen (92/105, 87.6 %, and 188/203, 92.6 %,
      respectively) and FF antigen (94/105, 89.5 %, and 188/203, 92.6 %, respectively).
      At a titre range of 1 : 400-1 : 800, statistically determined as the optimum cut
      off for the three antigens, sensitivities of 92.4, 90.5 and 96.2 % and
      specificities of 90.6, 90.1 and 88.7 % were achieved for the GP, FD and FF
      antigens, respectively, at a peripheral hospital. Regardless of the antigen
      preparation used, DAT results obtained in the peripheral hospital were highly
      reproducible in the central laboratory in Omdurman (weighted kappa: GP=0.957,
      FD=0.979 and FF=0.936). With a diagnostic reliability comparable to formaldehyde
      fixation and stability under ambient conditions similar to freeze drying,
      glycerol preservation, by virtue of its high potential for reproduction, meets
      the requirements for the management of VL in developing countries.

PMID- 17005783
TI  - PCR fingerprinting of Trichophyton mentagrophytes var. interdigitale using
      polymorphic subrepeat loci in the rDNA nontranscribed spacer.
AB  - The sequence of the nontranscribed spacer (NTS) region of the rDNA of
      Trichophyton mentagrophytes var. interdigitale strain 2111 was determined, and
      three individual subrepeat loci identified. The first repeat region contained
      eight tandem copies of a degenerate 33-43 bp sequence, whilst the second had two
      complete and two partial 300 bp repeats. The third locus contained six tandemly
      repetitive elements of between 67 and 89 bp, which showed sequence identity to
      the TrS2 repeats of Trichophyton rubrum. PCR amplification of the individual
      repetitive regions from 42 random isolates of T. mentagrophytes var.
      interdigitale identified fragment length polymorphisms at each locus. Sequence
      analysis of the PCR products revealed that the size variations resulted from
      differences in the copy number of each of the three sets of subrepeat elements,
      TmiS0, TmiS1 and TmiS2. In addition, some indels were present in the flanking
      regions of the TmiS1 repeats. Combining PCR fingerprints from each of the three
      polymorphic loci produced a total of 19 individual strain profiles. The method
      was rapid, reproducible and discriminatory, and the fragment patterns simple to
      interpret. PCR fingerprint analysis of variable tandem repeat loci in the T.
      mentagrophytes var. interdigitale NTS represents a valuable molecular typing
      method for future epidemiological investigations in this species.

PMID- 17005784
TI  - An open study of the comparative efficacy and safety of caspofungin and liposomal
      amphotericin B in treating invasive fungal infections or febrile neutropenia in
      patients with haematological malignancy.
AB  - In a clinical non-trial setting, the efficacy and safety of caspofungin was
      compared with liposomal amphotericin B for the management of febrile neutropenia
      or invasive fungal infections in 73 episodes in patients with haematological
      malignancy. There were fewer episodes of drug toxicity with caspofungin than
      liposomal amphotericin B (58.3 vs 83.7 %, P=0.02). The favourable response rate
      for episodes of febrile neutropenia treated with caspofungin or liposomal
      amphotericin B was similar at 37.5 and 53.8 %, respectively, but more
      breakthrough fungal infections occurred with caspofungin than with liposomal
      amphotericin B (33.3 vs 0 %, P<0.05) in these patients who did not receive
      antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic
      candidiasis responded to caspofungin compared with three of four episodes treated
      with liposomal amphotericin B. Mortality was significantly higher with
      caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49,
      P=0.01), mainly due to an excess of fungal infections (P=0.04). Caspofungin
      treatment was a significant independent predictor of mortality [odds ratio=7.6
      (95 % confidence interval 1.2-45.5)] when sepsis severity, prolonged neutropenia
      and length of antifungal therapy were considered in a multiple logistic
      regression model. In clinical practice, there is a suggestion that caspofungin
      may not be as effective as liposomal amphotericin B in preventing breakthrough
      invasive fungal infections in febrile neutropenia or in preventing fungus-related
      deaths. Because of the potential biases in this observational study, these
      preliminary findings should be interpreted with caution and clarified with a
      larger cohort of patients.

PMID- 17005786
TI  - In vitro activity of tea-tree oil against clinical skin isolates of meticillin
      resistant and -sensitive Staphylococcus aureus and coagulase-negative
      staphylococci growing planktonically and as biofilms.
AB  - The susceptibility of Staphylococcus aureus [meticillin-resistant (MRSA) and
      meticillin-sensitive (MSSA)] and coagulase-negative staphylococci (CoNS), which
      respectively form part of the transient and commensal skin flora, to tea-tree oil
      (TTO) was compared using broth microdilution and quantitative in vitro time-kill
      test methods. MRSA and MSSA isolates were significantly less susceptible than
      CoNS isolates, as measured by both MIC and minimum bactericidal concentration. A
      significant decrease in the mean viable count of all isolates in comparison with
      the control was seen at each time interval in time-kill assays. However, the only
      significant difference in the overall mean log10 reduction in viable count
      between the groups of isolates was between CoNS and MSSA at 3 h, with CoNS
      isolates demonstrating a significantly lower mean reduction. To provide a better
      simulation of in vivo conditions on the skin, where bacteria are reported to grow
      as microcolonies encased in glycocalyx, the bactericidal activity of TTO against
      isolates grown as biofilms was also compared. Biofilms formed by MSSA and MRSA
      isolates were completely eradicated following exposure to 5 % TTO for 1 h. In
      contrast, of the biofilms formed by the nine CoNS isolates tested, only five were
      completely killed, although a reduction in viable count was apparent for the
      other four isolates. These results suggest that TTO exerts a greater bactericidal
      activity against biofilm-grown MRSA and MSSA isolates than against some biofilm
      grown CoNS isolates.

PMID- 17005785
TI  - Antifungal activity of the essential oil of Thymus pulegioides on Candida,
      Aspergillus and dermatophyte species.
AB  - The composition of the essential oil of Thymus pulegioides and its antifungal
      activity on Candida, Aspergillus and dermatophyte fungal strains were studied.
      Essential oil from the aerial parts of the plant was obtained by
      hydrodistillation and analysed by GC and GC-MS. The oil showed high contents of
      carvacrol and thymol. The MIC and minimal lethal concentration were used to
      evaluate the antifungal activity against Candida (seven clinical isolates and
      four ATCC type strains), Aspergillus [five clinical isolates, and two Coleccion
      Espanola de Cultivos Tipo (CECT) and two ATCC type strains] and five clinical
      dermatophyte strains. Antifungal activity was evaluated for the essential oil and
      for its main components. To clarify its mechanism of action on yeasts and
      filamentous fungi, flow-cytometric studies of cytoplasmic membrane integrity were
      performed, and the effect on the amount of ergosterol was investigated. Results
      showed that T. pulegioides essential oil exhibited a significant activity against
      clinically relevant fungi, mainly due to lesion formation in the cytoplasmic
      membrane and a considerable reduction of the ergosterol content. The present
      study indicates that T. pulegioides essential oil has considerable antifungal
      activity, deserving further investigation for clinical applications.

PMID- 17005787
TI  - Immunization with 3-oxododecanoyl-L-homoserine lactone-protein conjugate protects
      mice from lethal Pseudomonas aeruginosa lung infection.
AB  - Quorum-sensing systems have been reported to play a critical role in the
      pathogenesis of several bacterial infections. Recent data have demonstrated that
      Pseudomonas N-3-oxododecanoyl-L-homoserine lactone (3-oxo-C12-homoserine lactone,
      3-oxo-C12-HSL), but not N-butanoyl-L-homoserine lactone (C4-HSL), induces
      apoptosis in macrophages and neutrophils. In the present study, the effects of
      active immunization with 3-oxo-C12-HSL-carrier protein conjugate on acute P.
      aeruginosa lung infection in mice were investigated. Immunization with 3-oxo-C12
      HSL-BSA conjugate (subcutaneous, four times, at 2-week intervals) elaborated
      significant amounts of specific antibody in serum. Control and immunized mice
      were intranasally challenged with approximately 3 x 10(6) c.f.u. P. aeruginosa
      PAO1, and survival was then compared. All control mice died by day 2 post
      bacterial challenge, while 36 % of immunized mice survived to day 4 (P<0.05).
      Interestingly, bacterial numbers in the lungs did not differ between control and
      immunized groups, whereas the levels of pulmonary tumour necrosis factor (TNF)
      alpha in the immunized mice were significantly lower than those of control mice
      (P<0.05). Furthermore, the extractable 3-oxo-C12-HSL levels in serum and lung
      homogenate were also significantly diminished in the immunized mice. Immune serum
      completely rescued reduction of cell viability by 3-oxo-C12-HSL-mediated
      apoptosis in macrophages in vitro. These results demonstrated that specific
      antibody to 3-oxo-C12-HSL plays a protective role in acute P. aeruginosa
      infection, probably through blocking of host inflammatory responses, without
      altering lung bacterial burden. The present data identify a promising potential
      vaccine strategy targeting bacterial quorum-sensing molecules, including
      autoinducers.

PMID- 17005788
TI  - Construction of a eukaryotic expression system for granulysin and its protective
      effect in mice infected with Mycobacterium tuberculosis.
AB  - A full-length cDNA of granulysin was inserted into the pcDNA3.1(-) vector to
      construct a eukaryotic expression plasmid for granulysin. The recombinant
      plasmids were injected intramuscularly into mice infected with Mycobacterium
      tuberculosis to evaluate the protective effect of granulysin. Granulysin
      significantly decreased the weight index (WI) of the spleen, reduced the numbers
      of viable bacteria in lung and spleen, and reduced the lesions of lung tissue in
      granulysin-rDNA-immunized mice compared with those of control group mice. In
      vitro, the serum of the recombinant-plasmid-immunized mice inhibited the
      viability of M. tuberculosis by the physical disruption of cell membranes.
      Therefore, granulysin has a therapeutic effect against M. tuberculosis.

PMID- 17005789
TI  - Topoisomerase mutations and efflux are associated with fluoroquinolone resistance
      in Enterococcus faecalis.
AB  - To understand better the mechanisms of fluoroquinolone resistance in Enterococcus
      faecalis, fluoroquinolone-resistant mutants isolated from Ent. faecalis ATCC
      29212 by stepwise selection with sparfloxacin (SPX) and norfloxacin (NOR) were
      analysed. The results showed the following. (i) In general, fluoroquinolone
      resistance mechanisms in Ent. faecalis are similar to those in other Gram
      positive bacteria, such as Staphylococcus aureus and Streptococcus pneumoniae,
      namely, mutants with amino acid changes in both GyrA and ParC exhibited high
      fluoroquinolone resistance, and single GyrA mutants and a single ParC mutant were
      more resistant to SPX and NOR, respectively, than the parent strain, indicating
      that the primary targets of SPX and NOR in Ent. faecalis are DNA gyrase and
      topoisomerase IV, respectively. (ii) Alterations in GyrB (DeltaKGA, residues 395
      397) and ParE (Glu-459 to Lys) were associated with fluoroquinolone resistance in
      some mutants. Moreover, the facts that the NOR MIC, but not the SPX MIC,
      decreased in the presence of multidrug efflux pump inhibitors, that NOR
      accumulation decreased in the cells, and that the EmeA mRNA expression level did
      not change, strongly suggested that a NorA-like efflux pump, rather than EmeA,
      was involved in resistance to NOR.

PMID- 17005790
TI  - The DNA-binding domain of CaNdt80p is required to activate CDR1 involved in drug
      resistance in Candida albicans.
AB  - CaNdt80p, the Candida albicans homologue of the Saccharomyces cerevisiae
      transcription factor ScNdt80p, has been identified as a positive regulator of
      CDR1, which encodes an efflux pump involved in drug resistance in C. albicans. To
      investigate the involvement of the putative DNA-binding domain of CaNdt80p in
      drug resistance, chimeras of CaNdt80p and ScNdt80p were constructed.
      Interestingly, the DNA-binding domain of ScNdt80p could functionally complement
      that of CaNdt80p to activate CDR1p-lacZ in S. cerevisiae. Consistently, CaNdt80p
      containing a mutation in the DNA-binding domain failed to activate CDR1p-lacZ in
      S. cerevisiae. Furthermore, a copy of CaNDT80 with the same mutation also failed
      to complement the drug-sensitive phenotype caused by a null mutation in C.
      albicans. Thus, the DNA-binding domain of CaNdt80p is critical for its function
      in drug resistance in C. albicans.

PMID- 17005791
TI  - Predominance of multi-drug-resistant LAM and Beijing family strains among
      Mycobacterium tuberculosis isolates recovered from prison inmates in Tula Region,
      Russia.
AB  - The genotypic characteristics and drug susceptibility profiles of clinical
      isolates of Mycobacterium tuberculosis recovered from prison hospital patients in
      the Tula region (central Russia) during 2001 and 2002 are reported. The emergence
      of multi-drug-resistant tuberculosis (TB) poses a major health risk to the
      population, with economic implications for TB control. Prisons serve as a
      continuous source of TB transmission. The results showed that members of the LAM
      and Beijing families are major contributors to the epidemiological picture of TB
      in the population studied. The two families of strains accounted for most of the
      drug-resistant TB in the population. The genotypic characteristics of the M.
      tuberculosis predominant LAM strain that was responsible for 31 % of TB cases in
      this setting are presented.

PMID- 17005792
TI  - Molecular characterization of clinical isolates of M non-typable group A
      streptococci from invasive disease cases.
AB  - Currently there are 93 validated M serotypes of Streptococcus pyogenes,
      Lancefield group A streptococcus (GAS), and >130 emm genotypes. A marked increase
      in the number of non-typable GAS isolates (2 % in 2000, 4 % in 2001 and 9 % in
      2002) from invasive disease cases referred to the authors' reference laboratory
      was noted during 2000-2002. A total of 217 (92 %) were from blood cultures, 14 (6
      %) from deep abscesses and five (2 %) from aspirates. The clinical manifestations
      included bacteraemia, septicaemia, cellulitis, meningitis, necrotizing fasciitis
      and toxic-shock syndrome. In order to establish whether this increase was due to
      the emergence of novel types or the unavailability of M-typing sera, these
      isolates were subjected to emm sequencing. A total of 144 isolates (61 %)
      belonged to M types for which sera were no longer available; 112 (48 %) belonged
      to higher M types, including emm83.1 (9 %), emm94 (8 %) emm87 (6 %) and emm89 (6
      %); and 32 (13 %) belonged to lower M types that were not commonly isolated in
      the UK, and included M25, M43, M49, M64, M73 and M74. Sixty-six (28 %) of the
      isolates belonged to newly designated emm types. Other isolates belonged to the
      novel emm types st2147, STNS1033 and st854, recently registered in the Centers
      for Disease Control (CDC) database by other laboratories. One novel emm type,
      st2161, was isolated from an injecting drug user. There were differences in the
      type distribution of these isolates according to geographic location. However, 90
      % of emm93, one of seven predominant emm types identified amongst the collection
      of M non-typable (MNT) isolates, were isolated from the London region.

PMID- 17005793
TI  - Clonal analysis of Inquilinus limosus isolates from six cystic fibrosis patients
      and specific serum antibody response.
AB  - Inquilinus limosus is a novel Gram-negative bacterium of the subdivision alpha
      Proteobacteria recently found in the airways of patients with cystic fibrosis
      (CF). Here, the authors report on the clinical courses of six CF patients
      colonized with I. limosus. Five patients suffered from either an acute
      respiratory exacerbation or a progressive loss of pulmonary function, whereas one
      patient was in a stable clinical situation. This study focused on two aims: (i)
      the clonal analysis of I. limosus isolates by random amplified polymorphic DNA
      (RAPD)-PCR, and (ii) the clarification of whether the presence of I. limosus in
      the respiratory tract is associated with a specific serum antibody response.
      Serum IgG was detected by immunoblotting using I. limosus whole-cell-lysate
      proteins as antigens. Sera from healthy blood donors (n=10) and from CF patients
      colonized with Pseudomonas aeruginosa (n=10) were found to be immunoblot
      negative. All six Inquilinus-positive patients raised serum IgG antibodies
      against various I. limosus antigens. Surprisingly, in one patient, a specific I.
      limosus serum antibody response was already detected 1 year prior to Inquilinus
      positive sputum cultures. Two prominent antigens were characterized by MALDI-MS:
      a 23 kDa protein revealed homology to the outer membrane lipoprotein OmlA of
      Actinobacillus pleuropneumoniae, and an 18 kDa protein to a protein-tyrosine
      phosphatase of Burkholderia cepacia. In conclusion, detection of I. limosus is
      accompanied by a specific serum antibody response and may reflect the
      infectious/pathogenic potential of I. limosus. Moreover, IgG immunoblotting may
      be useful to detect early infection with I. limosus and may support the selective
      cultivation of this novel emerging pathogen.

PMID- 17005794
TI  - Frequency and predictors of colonization of the respiratory tract by VIM-2
      producing Pseudomonas aeruginosa in patients of a newly established intensive
      care unit.
AB  - The aim of this study was to examine the frequency and predictors of colonization
      of the respiratory tract by metallo-beta-lactamase (MBL)-producing Gram-negative
      bacteria in patients admitted to a newly established intensive care unit (ICU) of
      a tertiary care hospital. Specimens of tracheobronchial aspirates for
      microbiological studies were obtained every day for the first 3 days of the ICU
      stay and subsequently every third day for the rest of the ICU stay. PCR analysis
      and nucleotide sequencing were performed to identify bacteria that had MBL genes.
      Thirty-five patients (20 male, 15 female) were hospitalized during the initial 3
      month period of functioning of the ICU. Colonization of the lower respiratory
      tract by Gram-negative bacteria was found in 29 of 35 patients (83 %) during the
      first 6-20 days (median 13 days) following admission to the ICU (13 patients with
      Acinetobacter baumannii, ten with Pseudomonas aeruginosa, three with Enterobacter
      aerogenes, two with Klebsiella pneumoniae and one with Stenotrophomonas
      maltophilia). Six of 29 patients (21 %) colonized with Gram-negative bacteria had
      bla(VIM-2)-positive P. aeruginosa isolates; one of these patients developed
      clinical infection due to this micro-organism. Previous use of carbapenems
      (P=0.01) or other beta-lactams (P=0.03), as well as a stay in the ICU of >20 days
      (P<0.001), were associated with colonization with bla(VIM-2)-producing P.
      aeruginosa. In conclusion, colonization by Gram-negative bacteria of the
      respiratory tract of patients in this newly established ICU was common (83 %).
      Use of beta-lactams, including carbapenems, was associated with subsequent
      colonization of the respiratory tract with MBL-positive P. aeruginosa.

PMID- 17005795
TI  - Synthesis and characterization of Pseudomonas aeruginosa alginate-tetanus toxoid
      conjugate.
AB  - Chronic infection with Pseudomonas aeruginosa is the main proven perpetrator of
      lung function decline and ultimate mortality in cystic fibrosis (CF) patients.
      Mucoid strains of this bacterium elaborate mucoid exopolysaccharide, also
      referred to as alginate. Alginate-based immunization of naive animals elicits
      opsonic antibodies and leads to clearance of mucoid P. aeruginosa from the lungs.
      Alginate was isolated from mucoid P. aeruginosa strain 8821M by repeated ethanol
      precipitation, dialysis, proteinase and nuclease digestion, and chromatography.
      To improve immunogenicity, the purified antigen was coupled to tetanus toxoid
      (TT) with adipic acid dihydrazide (ADH) as a spacer and 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide (EDAC) as a linker. The reaction mixture was
      passed through a Sepharose CL-4B column. The resulting conjugate was composed of
      TT and large-size alginate polymer at a ratio of about 3 : 1; it was non-toxic
      and non-pyrogenic, and elicited high titres of alginate-specific IgG. Antisera
      raised against the conjugate had high opsonic activity against the vaccine
      strain. The alginate conjugate was also able to protect mice against a lethal
      dose of mucoid P. aeruginosa. These data indicate that an alginate-based vaccine
      has significant potential to protect against chronic infection with mucoid P.
      aeruginosa in the CF host.

PMID- 17005796
TI  - Optimal sampling site for mucosal candidosis in oral cancer patients is the
      labial sulcus.
AB  - Traditional sampling methods for the diagnosis of oral candidosis in head and
      neck cancer patients, i.e. saliva collection or tongue scrapings, are often
      impossible to perform. The aim was to determine the optimal sampling method.
      Eighteen oral cancer patients and five control subjects were sampled semi
      quantitatively from the labial sulcus, dorsum of the tongue, dental plaque and
      saliva for cultivation of yeasts. The patients were examined prior to all cancer
      treatment (n=5), or 2-4 weeks (n=5) or 8-12 weeks (n=8) post-operatively. The
      incidence of Candida was found to increase from 40 % at the control and pre
      operative level up to 73 % 8-12 weeks post-operatively. Candida albicans was
      found to be the only species until 4 weeks post-operatively. Thereafter, the
      incidence of species other than C. albicans was 38 %. The most sensitive sampling
      site was found to be the vestibular sulcus, from which all culture-positive cases
      could be confirmed. Tongue surface scraping was found to be more sensitive than
      saliva collection in detecting Candida. All sampling methods and sites were
      equally sensitive in detecting the different Candida species. Dental plaque was
      found to have the highest density of Candida colonization, and was thus found to
      be the most significant source of Candida infection, which emphasizes the role of
      dental care in these patients.

PMID- 17005797
TI  - Primary bacteraemia caused by Rhizobium radiobacter in a patient with solid
      tumours.
AB  - A case of Rhizobium radiobacter primary bacteraemia in a patient with solid
      tumours is reported. Corticosteroid therapy and diabetes mellitus were the
      predisposing factors. The patient was treated successfully with amikacin and
      piperacillin/tazobactam. The clinical isolate was identified as R. radiobacter by
      16S rRNA gene sequencing. Phytopathogenicity tests and a PCR assay demonstrated
      that the organism was not a plant pathogen.

PMID- 17005798
TI  - Use of voriconazole in a patient with aspergilloma caused by an itraconazole
      resistant strain of Aspergillus fumigatus.
AB  - The case is reported of a patient with cavitary sarcoidosis complicated by an
      aspergilloma caused by an itraconazole-resistant strain of Aspergillus fumigatus,
      who was treated with voriconazole. The authors suggest that susceptibility
      testing of A. fumigatus strains is of value during long-term therapy with
      itraconazole, and that voriconazole may be a good option for treatment of
      patients infected with itraconazole-resistant strains of A. fumigatus.

PMID- 17005799
TI  - Resistance of Yersinia pestis to antimicrobial agents.

PMID- 17005800
TI  - Origins and evolution of methicillin-resistant Staphylococcus aureus clonal
      lineages.
AB  - Most methicillin-resistant Staphylococcus aureus (MRSA) isolates identified among
      blood isolates collected in Denmark between 1957 and 1970 belonged to either
      phage group III or the closely related 83A complex and had a PSTM antibiotype
      (resistance to penicillin [P], streptomycin [S], tetracycline [T], and
      methicillin [M]). Recently, some of these isolates were shown to have the same
      genetic backgrounds as contemporary epidemic MRSA isolates, and Danish
      methicillin-susceptible S. aureus (MSSA) isolates from the 1960s with a PST
      antibiotype were proposed to have been the recipients of the mecA gene in those
      lineages. In this study, we investigated the genetic backgrounds of isolates from
      the 83A complex that were fully susceptible or resistant to penicillin only in
      order to try to trace the evolutionary trajectory of contemporary MRSA lineages.
      We also studied MSSA and MRSA isolates from other phage groups in order to
      investigate if they had the potential to develop into contemporary MRSA clones.
      Most susceptible or penicillin-resistant isolates from phage group III or the 83A
      complex belonged to sequence type 8 (ST8) or ST5, while four isolates were ST254.
      STs 30, 45 and 25 were represented by MSSA isolates from other phage groups,
      which also included several singletons. Representatives of most of the current
      major epidemic MRSA lineages were identified among fully susceptible isolates
      collected in the 1960s, suggesting that these were MSSA lineages which carried
      genetic traits important for superior epidemicity before the acquisition of
      methicillin resistance.

PMID- 17005801
TI  - Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per
      kilogram of body weight once daily in healthy volunteers.
AB  - Daptomycin, a novel lipopeptide, is bactericidal against a broad range of gram
      positive strains, including methicillin- (MRSA) and vancomycin-resistant
      Staphylococcus aureus. Daptomycin is approved at 4 mg/kg of body weight given
      intravenously once daily for the treatment of complicated skin and skin structure
      infections and at 6 mg/kg for the treatment of S. aureus bloodstream infections
      (bacteremia), including right-sided endocarditis caused by methicillin
      susceptible S. aureus and MRSA. The present study was designed to evaluate the
      multiple-dose pharmacokinetics and safety of daptomycin at doses of 6 to 12 mg/kg
      in healthy volunteers. Three cohorts of 12 subjects each were given daptomycin
      (10 mg/kg) or placebo once daily for 14 days, daptomycin (12 mg/kg) or placebo
      once daily for 14 days, or daptomycin (6 or 8 mg/kg) once daily for 4 days.
      Daptomycin produced dose-proportional increases in the area under the plasma
      concentration-time curve and in trough daptomycin levels and nearly dose
      proportional increases in peak daptomycin concentrations. Other pharmacokinetic
      parameters measured on day 1 and at steady state were independent of the dose,
      including the half-life (approximately 8 h), weight-normalized plasma clearance
      (9 to 10 ml/h/kg), and volume of distribution (approximately 100 ml/kg). Plasma
      protein binding was 90% to 93% and was independent of the daptomycin
      concentration. Daptomycin did not produce electrocardiographic abnormalities or
      electrophysiological evidence of muscle or nerve toxicity. Daptomycin was well
      tolerated in subjects dosed with up to 12 mg/kg intravenously for 14 days. Doses
      of daptomycin higher than 6 mg/kg once daily may be considered in further studies
      to evaluate the safety and efficacy of daptomycin in difficult-to-treat
      infections.

PMID- 17005802
TI  - Engineered vaginal lactobacillus strain for mucosal delivery of the human
      immunodeficiency virus inhibitor cyanovirin-N.
AB  - Women are at significant risk of human immunodeficiency virus (HIV) infection,
      with the cervicovaginal mucosa serving as a major portal for virus entry. Female
      initiated preventatives, including topical microbicides, are urgently needed to
      help curtail the HIV/AIDS pandemic. Here we report on the development of a novel,
      live microbicide that employs a natural vaginal strain of Lactobacillus jensenii
      engineered to deliver the potent HIV inhibitor cyanovirin-N (CV-N). To facilitate
      efficient expression of CV-N by this bacterium, the L. jensenii 1153 genome was
      sequenced, allowing identification of native regulatory elements and sites for
      the chromosomal integration of heterologous genes. A CV-N expression cassette was
      optimized and shown to produce high levels of structurally intact CV-N when
      expressed in L. jensenii. Lactobacillus-derived CV-N was capable of inhibiting
      CCR5-tropic HIV(BaL) infectivity in vitro with a 50% inhibitory concentration of
      0.3 nM. The CV-N expression cassette was stably integrated as a single copy into
      the bacterial chromosome and resolved from extraneous plasmid DNA without
      adversely affecting the bacterial phenotype. This bacterial strain was capable of
      colonizing the vagina and producing full-length CV-N when administered
      intravaginally to mice during estrus phase. The CV-N-producing Lactobacillus was
      genetically stable when propagated in vitro and in vivo. This work represents a
      major step towards the development of an inexpensive yet durable protein-based
      microbicide to block the heterosexual transmission of HIV in women.

PMID- 17005804
TI  - Biofilm formation by the emerging fungal pathogen Trichosporon asahii:
      development, architecture, and antifungal resistance.
AB  - Trichosporon asahii is the most common cause of fatal disseminated
      trichosporonosis, frequently associated with indwelling medical devices. Despite
      the use of antifungal drugs to treat trichosporonosis, infection is often
      persistent and is associated with high mortality. This drove our interest in
      evaluating the capability of T. asahii to form a biofilm on biomaterial
      representative polystyrene surfaces through the development and optimization of a
      reproducible T. asahii-associated biofilm model. Time course analyses of viable
      counts and a formazan salt reduction assay, as well as microscopy studies,
      revealed that biofilm formation by T. asahii occurred in an organized fashion
      through four distinct developmental phases: initial adherence of yeast cells (0
      to 2 h), germination and microcolony formation (2 to 4 h), filamentation (4 to 6
      h), and proliferation and maturation (24 to 72 h). Scanning electron microscopy
      and confocal scanning laser microscopy revealed that mature T. asahii biofilms
      (72-h) displayed a complex, heterogeneous three-dimensional structure, consisting
      of a dense network of metabolically active yeast cells and hyphal elements
      completely embedded within exopolymeric material. Antifungal susceptibility
      testing demonstrated a remarkable rise in the MICs of sessile T. asahii cells
      against clinically used amphotericin B, caspofungin, voriconazole, and
      fluconazole compared to their planktonic counterparts. In particular, T. asahii
      biofilms were up to 16,000 times more resistant to voriconazole, the most active
      agent against planktonic cells (MIC, 0.06 microg/ml). Our results suggest that
      the ability of T. asahii to form a biofilm may be a major factor in determining
      persistence of the infection in spite of in vitro susceptibility of clinical
      isolates.

PMID- 17005803
TI  - Novel robust hepatitis C virus mouse efficacy model.
AB  - The lack of a robust small-animal model for hepatitis C virus (HCV) has hindered
      the discovery and development of novel drug treatments for HCV infections. We
      developed a reproducible and easily accessible xenograft mouse efficacy model in
      which HCV RNA replication is accurately monitored in vivo by real-time,
      noninvasive whole-body imaging of gamma-irradiated SCID mice implanted with a
      mouse-adapted luciferase replicon-containing Huh-7 cell line (T7-11). The model
      was validated by demonstrating that both a small-molecule NS3/4A protease
      inhibitor (BILN 2061) and human alpha interferon (IFN-alpha) decreased HCV RNA
      replication and that treatment withdrawal resulted in a rebound in replication,
      which paralleled clinical outcomes in humans. We further showed that protease
      inhibitor and IFN-alpha combination therapy was more effective in reducing HCV
      RNA replication than treatment with each compound alone and supports testing in
      humans. This robust mouse efficacy model provides a powerful tool for rapid
      evaluation of potential anti-HCV compounds in vivo as part of aggressive drug
      discovery efforts.

PMID- 17005805
TI  - Effect of PEX, a noncatalytic metalloproteinase fragment with integrin-binding
      activity, on experimental Chlamydophila pneumoniae infection.
AB  - Chlamydophila pneumoniae is a pathogen that is involved in acute and chronic
      respiratory infections and that is associated with asthma and coronary artery
      diseases. In this study, we evaluated the effects of PEX, a noncatalytic
      metalloproteinase fragment with integrin-binding activity, against experimental
      infections caused by C. pneumoniae. Moreover, we investigated the relationships
      between C. pneumoniae and alpha(v)beta(3) integrin functions in order to explain
      the possible mechanism of action of PEX both in vitro and in vivo. For the in
      vitro experiments, HeLa cells were infected with C. pneumoniae and treated with
      either PEX or azithromycin. The results obtained with PEX were not significantly
      different (P > 0.05) from those achieved with azithromycin. Similar results were
      also obtained in a lung infection model. Male C57BL/J6 mice inoculated
      intranasally with 10(6) inclusion-forming units of C. pneumoniae were treated
      with either PEX or azithromycin plus rifampin. Infected mice treated with PEX
      showed a marked decrease in C. pneumoniae counts versus those for the controls;
      this finding did not differ significantly (P > 0.05) from the results observed
      for the antibiotic-treated group. Integrin alpha(v)beta(3) plays an important
      role in C. pneumoniae infection. Blockage of integrin activation led to a
      significant inhibition of C. pneumoniae infection in HeLa cells. Moreover,
      CHO(DHFR) alpha(v)beta(3)-expressing cells were significantly (P < 0.001) more
      susceptible to C. pneumoniae infection than CHO(DHFR) cells. These results offer
      new perspectives on the treatment of C. pneumoniae infection and indicate that
      alpha(v)beta(3) could be a promising target for new agents developed for activity
      against this pathogen.

PMID- 17005806
TI  - Comparative in vitro efficacies and antimicrobial durabilities of novel
      antimicrobial central venous catheters.
AB  - We investigated the efficacies and durability of novel antimicrobial central
      venous catheters (CVCs) in preventing the adherence of microbial organisms to the
      surfaces of the CVCs. Novel antimicrobial CVCs investigated in this in vitro
      study were impregnated with antibiotics (minocycline and rifampin), with Oligon
      agent (silver, platinum, and carbon black), with approved antiseptics
      (chlorhexidine and silver sulfadiazine), or with a novel antiseptic agent,
      gendine, which contains gentian violet and chlorhexidine. When tested against
      methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa,
      gendine-coated CVC segments provided protection against bacterial adherence
      significantly more than all other types of tested CVCs (P < 0.05). Gendine-coated
      CVCs also provided better protection against Candida albicans and Candida
      parapsilosis than CVCs impregnated with antibiotics or with silver, platinum, and
      carbon (P < 0.02). After 28 days of being soaked in serum, the CVCs impregnated
      with chlorhexidine and silver sulfadiazine and the CVCs impregnated with silver,
      platinum, and carbon had lost antimicrobial activity against MRSA, P. aeruginosa,
      and C. parapsilosis, and the CVCs impregnated with minocycline and rifampin had
      lost activity against P. aeruginosa and C. parapsilosis. The CVCs impregnated
      with gendine maintained antimicrobial activities against MRSA, P. aeruginosa, and
      C. parapsilosis after 28 days of being soaked in serum. Central venous catheters
      impregnated with the novel investigational antiseptic gendine showed in vitro
      efficacy and provided protection against bacterial adherence more than other
      approved novel antimicrobial-coated CVCs.

PMID- 17005807
TI  - Potent antiviral synergy between monoclonal antibody and small-molecule CCR5
      inhibitors of human immunodeficiency virus type 1.
AB  - The chemokine receptor CCR5 provides a portal of entry for human immunodeficiency
      virus type 1 (HIV-1) into susceptible CD4(+) cells. Both monoclonal antibody
      (MAb) and small-molecule CCR5 inhibitors have entered human clinical testing, but
      little is known regarding their potential interactions. We evaluated the
      interactions between CCR5 MAbs, small-molecule CCR5 antagonists, and inhibitors
      of HIV-1 gp120, gp41, and reverse transcriptase in vitro. Inhibition data were
      analyzed for cooperative effects using the combination index (CI) method and
      stringent statistical criteria. Potent, statistically significant antiviral
      synergy was observed between the CCR5 MAb PRO 140 and the small-molecule CCR5
      antagonists maraviroc (UK-427,857), vicriviroc (SCH-D), and TAK-779. High-level
      synergy was observed consistently across various assay systems, HIV-1 envelopes,
      CCR5 target cells, and inhibition levels. CI values ranged from 0.18 to 0.64 and
      translated into in vitro dose reductions of up to 14-fold. Competition binding
      studies revealed nonreciprocal patterns of CCR5 binding by MAb and small-molecule
      CCR5 inhibitors, suggesting that synergy occurs at the level of receptor binding.
      In addition, both PRO 140 and maraviroc synergized with the chemokine RANTES, a
      natural ligand for CCR5; however, additive effects were observed for both small
      molecule CCR5 antagonists and PRO 140 in combination with other classes of HIV-1
      inhibitors. The findings provide a rationale for clinical exploration of MAb and
      small-molecule CCR5 inhibitors in novel dual-CCR5 regimens for HIV-1 therapy.

PMID- 17005808
TI  - Mechanism of active renal tubular efflux of tenofovir.
AB  - Tenofovir (TFV) undergoes renal elimination by a combination of glomerular
      filtration and active tubular secretion. While transporter-mediated uptake of TFV
      from the blood into proximal-tubule cells has been well characterized,
      comparatively little is known about the efflux system responsible for
      transporting TFV into the lumen during active tubular secretion. Therefore,
      members of the ATP-binding cassette family of efflux pumps expressed at the
      apical side of proximal-tubule cells were studied for the ability to transport
      TFV. Studies in multiple independent in vitro systems show TFV not to be a
      substrate for P glycoprotein (Pgp) or multidrug resistance protein type 2 (MRP2).
      In contrast to Pgp and MRP2, TFV was observed to be a substrate for MRP4. TFV
      accumulated to fivefold lower levels in MRP4-overexpressing cells, and its
      accumulation could be increased by an MRP inhibitor. Furthermore, MRP4
      overexpressing cells were found to be 2.0- to 2.5-fold less susceptible to
      cytotoxicity caused by TFV. ATP-dependent uptake of TFV was observed in membrane
      vesicles containing MRP4 but not in vesicles lacking the transporter. On the
      basis of these and previous results, the molecular transport pathway for the
      active tubular secretion of TFV through renal proximal-tubule cells involves
      uptake from the blood mediated by human organic anion transporters 1 and 3 and
      efflux into urine by MRP4. A detailed understanding of the molecular mechanism of
      TFV active tubular secretion will facilitate the assessment of potential renal
      drug-drug interactions with coadministered agents.

PMID- 17005809
TI  - Enhanced membrane disruption and antibiotic action against pathogenic bacteria by
      designed histidine-rich peptides at acidic pH.
AB  - The histidine-rich amphipathic cationic peptide LAH4 has antibiotic and DNA
      delivery capabilities. Here, we explore the interaction of peptides from this
      family with model membranes as monitored by solid-state (2)H nuclear magnetic
      resonance and their antibiotic activities against a range of bacteria. At neutral
      pH, the membrane disruption is weak, but at acidic pH, the peptides strongly
      disturb the anionic lipid component of bacterial membranes and cause bacterial
      lysis. The peptides are effective antibiotics at both pH 7.2 and pH 5.5, although
      the antibacterial activity is strongly affected by the change in pH. At neutral
      pH, the LAH peptides were active against both methicillin-resistant and 
      sensitive Staphylococcus aureus strains but ineffective against Pseudomonas
      aeruginosa. In contrast, the LAH peptides were highly active against P.
      aeruginosa in an acidic environment, as is found in the epithelial-lining fluid
      of cystic fibrosis patients. Our results show that modest antibiotic activity of
      histidine-rich peptides can be dramatically enhanced by inducing membrane
      disruption, in this case by lowering the pH, and that histidine-rich peptides
      have potential as future antibiotic agents.

PMID- 17005810
TI  - Inhibition of filamentation can be used to treat disseminated candidiasis.
AB  - Candida albicans remains the leading causative agent of invasive fungal
      infection. Although the importance of filamentation in C. albicans pathogenesis
      has been extensively investigated, in vivo studies to date have been unable to
      dissect the role of this developmental process in the establishment of infection
      versus the development of active disease as characterized by damage to the host
      leading to mortality. To address this issue, we genetically engineered a C.
      albicans tet-NRG1 strain in which filamentation and virulence can be modulated
      both in vitro and in vivo simply by the presence or absence of doxycycline (DOX):
      this strain enabled us, in a prior study, to demonstrate that yeast-form cells
      were able to infect the deep organs but caused no disease unless filamentation
      (induced by the addition of DOX) was allowed to occur. In the present study, we
      examined whether inhibiting filamentation (by withdrawing the DOX) at 24 or 48 h
      postinfection could serve as an effective therapeutic intervention against
      candidiasis. The results obtained indicate that DOX removal led to an alteration
      in the morphology of the infecting fungal cells and a dramatic increase in
      survival, but as with conventional antifungal drug therapy regimens, mortality
      rates increased markedly the longer this intervention was delayed. These
      observations reinforce the importance of invasive filamentous growth in causing
      the damage to the host and the lethality associated with active disease and
      suggest this process could be fruitfully targeted for the development of new
      antifungal agents.

PMID- 17005811
TI  - Total variation in the penA gene of Neisseria meningitidis: correlation between
      susceptibility to beta-lactam antibiotics and penA gene heterogeneity.
AB  - In recent decades, the prevalence of Neisseria meningitidis isolates with reduced
      susceptibility to penicillins has increased. The intermediate resistance to
      penicillin (Pen(i)) for most strains is due mainly to mosaic structures in the
      penA gene, encoding penicillin-binding protein 2. In this study, susceptibility
      to beta-lactam antibiotics was determined for 60 Swedish clinical N. meningitidis
      isolates and 19 reference strains. The penA gene was sequenced and compared to
      237 penA sequences from GenBank in order to explore the total identified
      variation of penA. The divergent mosaic alleles differed by 3% to 24% compared to
      those of the designated wild-type penA gene. By studying the final 1,143 to 1,149
      bp of penA in a sequence alignment, 130 sequence variants were identified. In a
      402-bp alignment of the most variable regions, 84 variants were recognized. Good
      correlation between elevated MICs and the presence of penA mosaic structures was
      found especially for penicillin G and ampicillin. The Pen(i) isolates comprised
      an MIC of >0.094 microg/ml for penicillin G and an MIC of >0.064 microg/ml for
      ampicillin. Ampicillin was the best antibiotic for precise categorization as
      Pen(s) or Pen(i). In comparison with the wild-type penA sequence, two specific
      Pen(i) sites were altered in all except two mosaic penA sequences, which were
      published in GenBank and no MICs of the corresponding isolates were described. In
      conclusion, monitoring the relationship between penA sequences and MICs to
      penicillins is crucial for developing fast and objective methods for
      susceptibility determination. By studying the penA gene, genotypical
      determination of susceptibility in culture-negative cases can also be
      accomplished.

PMID- 17005812
TI  - Ciprofloxacin-resistant gram-negative bacilli in the fecal microflora of
      children.
AB  - The extent to which antibiotic-resistant bacteria are excreted by humans who have
      not been exposed to antibiotics is not known. Children, who rarely receive
      fluoroquinolones, provide opportunities to assess the frequency of fecal
      excretion by fluoroquinolone-naive hosts of fluoroquinolone-resistant gram
      negative bacilli. Fresh nondiarrheal stools from children were processed by
      screening them on agar containing ciprofloxacin to recover ciprofloxacin
      resistant gram-negative bacilli. Resistant isolates were identified, and
      ciprofloxacin MICs were determined. Resistant Escherichia coli isolates were also
      analyzed for urovirulence-associated loci. Thirteen (2.9%) of 455 stools yielded
      ciprofloxacin-resistant E. coli (seven children), Stenotrophomonas maltophilia
      (four children), and Achromobacter xylosoxidans and Enterobacter aerogenes (one
      child each). Neither the subjects themselves nor members of their households used
      fluoroquinolones in the 4 weeks preceding collection. Six of the seven resistant
      E. coli isolates belonged to phylogenetic groups B2 and D, in which
      extraintestinal pathogenic E. coli bacteria are frequently found. All resistant
      E. coli isolates contained at least three putative E. coli virulence loci. Most
      ciprofloxacin-resistant bacteria were resistant to additional antibiotics.
      Potentially pathogenic bacteria that are resistant to therapeutically important
      antimicrobial agents are excreted by some humans, despite these persons' lack of
      exposure to the particular drugs. The sources of these resistant organisms are
      unknown. This underrecognized reservoir of drug-resistant potential pathogens
      poses public health challenges.

PMID- 17005813
TI  - High-throughput and facile assay of antimicrobial peptides using pH-controlled
      fluorescence resonance energy transfer.
AB  - Amphipathic antimicrobial peptides can destroy bacteria cells by inducing
      membrane permeabilization, forming one strategy for innate defense by various
      organisms. However, although the antimicrobial peptides are considered a
      promising alternative for use against multidrug-resistant bacteria, large-scale
      screening of potential candidate antimicrobial peptides will require a simple,
      rapid assay for antimicrobial activity. Here, we describe a novel fluorescence
      resonance energy transfer (FRET)-based assay system for antimicrobial peptides
      which takes advantage of pH-related changes in FRET efficiency due to the
      instability of enhanced yellow fluorescent protein versus the stability of
      enhanced cyan fluorescent protein in a reduced-pH environment. We successfully
      showed that quantification of antimicrobial activity is possible through a
      difference of FRET efficiency between ECFP-EYFP fusion molecules released from
      disrupted Escherichia coli in an extracellular environment (pH 6) and those
      retained in an intracellular environment (pH approximately 7). Thus, we herein
      suggest a new simple, effective, and efficient pH-controlled FRET-based
      antimicrobial peptide screening method applicable to high-throughput screening of
      candidate peptide libraries.

PMID- 17005814
TI  - Effect of rifampin on steady-state pharmacokinetics of atazanavir with ritonavir
      in healthy volunteers.
AB  - Mycobacterium tuberculosis is a concern in patients with human immunodeficiency
      virus (HIV) infection. Rifampin (RIF), an agent used against M. tuberculosis, is
      contraindicated with most HIV protease inhibitors. Atazanavir (ATV) has clinical
      efficacy comparable to a standard of care regimen in naive patients and, when
      dosed with low-dose ritonavir (RTV), also in treatment-experienced patients. We
      evaluated here the safety and pharmacokinetics of ATV, resulting from three
      regimens of ATV, RTV, and RIF in 71 healthy subjects. The pharmacokinetics for
      ATV and RTV were assessed after 6 and 10 days of dosing with ATV 400 mg (n = 53)
      and with ATV-RTV at 300 and 100 mg (ATV/RTV 300/100; n = 52), respectively.
      Steady-state pharmacokinetics for ATV, RTV, RIF, and desacetyl-rifampin (des-RIF)
      were measured after 10 days of dosing of ATV/RTV/RIF 300/100/600 (n = 17),
      ATV/RTV/RIF 300/200/600 (n = 17), or ATV/RTV/RIF 400/200/600 (n = 14). An RIF 600
      alone arm was enrolled as a control group (n = 18). With ATV/RTV/RIF 400/200/600,
      ATV area under the concentration-time curve values were comparable, but the
      C(min) values were lower relative to ATV 400 alone. ATV exposures were
      substantially reduced for the other RIF-containing regimens relative to ATV 400
      alone and for all regimens relative to ATV/RTV 300/100 alone. RIF and des-RIF
      exposures were 1.6- to 2.5-fold higher than with RIF 600 alone. The incidence of
      grade 3/4 alanine aminotransferase/aspartate aminotransferase values was limited
      to 1 subject each in both the ATV/RTV/RIF 300/200/600 and the ATV/RTV/RIF
      400/200/600 treatments. Coadministration of ATV with RIF was safe and generally
      well tolerated. Since ATV exposures were reduced in all regimens, ATV and RIF
      should not be coadministered at the dosing regimens studied.

PMID- 17005815
TI  - Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates
      from africa by using a Plasmodium lactate dehydrogenase immunodetection assay and
      an inhibitory maximum effect model for precise measurement of the 50-percent
      inhibitory concentration.
AB  - The extension of drug resistance among malaria-causing Plasmodium falciparum
      parasites in Africa necessitates implementation of new combined therapeutic
      strategies. Drug susceptibility phenotyping requires precise measurements. Until
      recently, schizont maturation and isotopic in vitro assays were the only methods
      available, but their use was limited by technical constraints. This explains the
      revived interest in the development of replacement methods, such as the
      Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a
      commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA
      Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug
      susceptibility in a standard in vitro assay using fairly basic laboratory
      equipment to study the in vitro resistance of malaria parasites to major
      antimalarials. Five Plasmodium falciparum clones and 121 clinical African
      isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8
      (3)H]hypoxanthine isotopic assay as a reference with four antimalarials.
      Nonlinear regression with a maximum effect model was used to estimate the 50%
      inhibitory concentration (IC(50)) and its confidence intervals. The two methods
      were observed to have similar reproducibilities, but the pLDH ELISA demonstrated
      a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic
      agreement (kappa = 0.88) between the two methods allowed comparison by
      determination of the IC(50)s. Recently collected Plasmodium falciparum African
      isolates were tested by pLDH ELISA and showed drug resistance or decreased
      susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of
      amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite
      of artemisinin was detected. The availability of this simple and highly sensitive
      pLDH immunodetection assay will provide an easier method for drug susceptibility
      testing of malaria parasites.

PMID- 17005816
TI  - Mycobacterium leprae is naturally resistant to PA-824.
AB  - Leprosy responds very slowly to the current multidrug therapy, and hence there is
      a need for novel drugs with potent bactericidal activity. PA-824 is a 4
      nitroimidazo-oxazine that is currently undergoing phase I clinical trials for the
      treatment of tuberculosis. The activity of PA-824 against Mycobacterium leprae
      was tested and compared with that of rifampin in axenic cultures, macrophages,
      and two different animal models. Our results conclusively demonstrate that PA-824
      has no effect on the viability of M. leprae in all three models, consistent with
      the lack of the nitroimidazo-oxazine-specific nitroreductase, encoded by Rv3547
      in the M. leprae genome, which is essential for activation of this molecule.

PMID- 17005817
TI  - Impact of inactive empiric antimicrobial therapy on inpatient mortality and
      length of stay.
AB  - The consequences of inactive empiric antimicrobial therapy are not well-described
      and may cause prolonged hospitalization or infection-related mortality. In vitro
      susceptibility results for 884 patients hospitalized at an academic medical
      center with gram-negative bloodstream infections (GNBI) from 2001 to 2003 were
      matched to antimicrobial orders within 24 h of culture. Clinical characteristics,
      organism, inpatient mortality, and length of stay after culture for patients with
      GNBI were compared between patients receiving active versus inactive empiric
      antimicrobial therapy. A total of 14.1% of patients with GNBI received inactive
      empiric therapy, defined as no antimicrobial therapy within 24 h of the culture
      active against the identified organism based on in vitro microbiology reports.
      Patients who received inactive therapy were more likely to be younger, to be
      infected with Pseudomonas aeruginosa, to have a nosocomial infection, and to
      receive antimicrobial monotherapy but less likely to be bacteremic with
      Escherichia coli or to have sepsis (P < 0.05). There were no significant
      differences in mortality between patients receiving active versus inactive
      empiric therapy (16.1% versus 13.6%, respectively) or in length of stay after
      positive culture (11.5 days versus 12.6 days, respectively). Only 45 patients had
      greater than 2 days of exposure to inactive therapy; however, 8/30 patients
      (26.7%) who never received active antimicrobial therapy died while in the
      hospital. Inactive empiric therapy was more common in healthier patients.
      Inactive antimicrobial therapy in the first 24 h did not significantly impact
      average outcomes for GNBI among hospitalized patients but may have caused harm to
      specific individuals.

PMID- 17005818
TI  - The mef(E)-carrying genetic element (mega) of Streptococcus pneumoniae: insertion
      sites and association with other genetic elements.
AB  - The structure of the macrolide efflux genetic assembly (mega) element, its
      genomic locations, and its association with other resistance determinants and
      genetic elements were investigated in 16 Streptococcus pneumoniae isolates
      carrying mef(E), of which 1 isolate also carried tet(M) and 4 isolates also
      carried tet(M) and erm(B). All isolates carried a mega element of similar size
      and structure that included the operon mef(E)-msr(D) encoding the efflux
      transport system. Among tetracycline-susceptible isolates, six different
      integration sites were identified, five of which were recognized inside open
      reading frames present in the R6 genome. In the five isolates also carrying
      tet(M), mega was inserted in different genetic contexts. In one isolate, it was
      part of previously described Tn916-like element Tn2009. In another isolate, mega
      was inserted in a transposon similar to Tn2009 that also included an erm(B)
      element. This new composite transposon was designated Tn2010. Neither Tn2009 nor
      Tn2010 could be transferred by conjugation to pneumococcal or enterococcal
      recipients. In the three isolates in which mega was not physically linked with
      tet(M), this gene was associated with erm(B) in transposon Tn3872, a Tn916-like
      element. Homologies between the chromosomal insertions of these composite
      transposons and sequences of multidrug-resistant pneumococcal genomes in the
      databases indicate the presence of preferential sites for the integration of
      composite Tn916-like elements carrying multiple resistance determinants in S.
      pneumoniae.

PMID- 17005820
TI  - Effect of tigecycline on normal oropharyngeal and intestinal microflora.
AB  - Antibacterial agents disrupt the ecological balance of the normal human
      microflora. Tigecycline, a member of a new class of antibiotics (glycylcyclines),
      has been shown to have a potent broad-spectrum activity against most gram
      positive and gram-negative aerobic and anaerobic bacteria. The aim of the study
      was to investigate the ecological effects of tigecycline on the normal
      oropharyngeal and intestinal microflora of healthy subjects. Thirteen healthy
      white subjects (six females and seven males) between 20 and 31 years of age
      received 100 mg of tigecycline in the morning on day 1 as a 30-min intravenous
      infusion followed by a 50-mg dose of tigecycline every 12 h as a 30-minute
      infusion for 10 days. One subject was withdrawn on day 2 because of an adverse
      event (urticaria). Serum, saliva, and fecal samples were collected before,
      during, and after administration for microbiological cultivation and for assays
      of tigecycline. All new colonizing bacteria were tested for susceptibility
      (resistance of > or =8 mg/liter) during the investigation period. The fecal
      concentrations on day 8 were from 3.0 to 14.1 mg/kg, with a mean value of 6.0
      mg/kg and a median value of 5.6 mg/kg. The saliva concentrations were generally
      low (0 to 0.12 mg/liter). A minor effect on the oropharyngeal microflora was
      observed. The numbers of enterococci and Escherichia coli cells in the intestinal
      microflora were reduced at day 8 (P < 0.05), while those of other enterobacteria
      and yeasts increased. There was a marked reduction of lactobacilli and
      bifidobacteria (P < 0.05) but no impact on bacteroides. No Clostridium difficile
      strains were isolated. Two Klebsiella pneumoniae strains and five Enterobacter
      cloacae strains resistant to tigecycline were found on day 8.

PMID- 17005819
TI  - Bile salt-stimulated lipase from human milk binds DC-SIGN and inhibits human
      immunodeficiency virus type 1 transfer to CD4+ T cells.
AB  - A wide range of pathogens, including human immunodeficiency virus type 1 (HIV-1),
      hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, Mycobacterium,
      Leishmania, and Helicobacter pylori, can interact with dendritic cell (DC)
      specific ICAM3-grabbing nonintegrin (DC-SIGN), expressed on DCs and a subset of B
      cells. More specifically, the interaction of the gp120 envelope protein of HIV-1
      with DC-SIGN can facilitate the transfer of virus to CD4+ T lymphocytes in trans
      and enhance infection. We have previously demonstrated that a multimeric LeX
      component in human milk binds to DC-SIGN, preventing HIV-1 from interacting with
      this receptor. Biochemical analysis reveals that the compound is heat resistant,
      trypsin sensitive, and larger than 100 kDa, indicating a specific glycoprotein as
      the inhibitory compound. By testing human milk from three different mothers, we
      found the levels of DC-SIGN binding and viral inhibition to vary between samples.
      Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western
      blotting, and matrix-assisted laser desorption ionization analysis, we identified
      bile salt-stimulated lipase (BSSL), a Lewis X (LeX)-containing glycoprotein found
      in human milk, to be the major variant protein between the samples. BSSL isolated
      from human milk bound to DC-SIGN and inhibited the transfer of HIV-1 to CD4+ T
      lymphocytes. Two BSSL isoforms isolated from the same human milk sample showed
      differences in DC-SIGN binding, illustrating that alterations in the BSSL forms
      explain the differences observed. These results indicate that variations in BSSL
      lead to alterations in LeX expression by the protein, which subsequently alters
      the DC-SIGN binding capacity and the inhibitory effect on HIV-1 transfer.
      Identifying the specific molecular interaction between the different forms may
      aid in the future design of antimicrobial agents.

PMID- 17005821
TI  - Potent antihematozoan activity of novel bisthiazolium drug T16: evidence for
      inhibition of phosphatidylcholine metabolism in erythrocytes infected with
      Babesia and Plasmodium spp.
AB  - A leading bisthiazolium drug, T16, designed to mimic choline, was shown to exert
      potent antibabesial activity, with 50% inhibitory concentrations of 28 and 7 nM
      against Babesia divergens and B. canis, respectively. T16 accumulated inside
      Babesia-infected erythrocytes (cellular accumulation ratio, >60) by a saturable
      process with an apparent K(m) of 0.65 microM. Subcellular fractionation of
      Babesia parasites revealed the accumulation of T16 into a low-density fraction,
      while in malaria-infected erythrocytes a significant fraction of the drug was
      associated with heme malaria pigment. T16 exerts an early and specific inhibition
      of the de novo biosynthesis of phosphatidylcholine both in B. divergens- and
      Plasmodium falciparum-infected erythrocytes. Choline accumulation into isolated
      Babesia parasites was highly sensitive to inhibition by T16. These data are
      consistent with the hypothesis that bisthiazolium drugs target the de novo
      phosphatidylcholine biosynthesis of intraerythrocytic hematozoan parasites. In
      malaria parasites, which generate ferriprotoporphyrin IX during hemoglobin
      digestion, T16 binding to heme may enhance the accumulation and activity of the
      drug. The selectivity of accumulation and potent activity of this class of drug
      into parasite-infected erythrocytes offers unique advantages over more
      traditional antihematozoan drugs.

PMID- 17005822
TI  - High-level carbapenem resistance in a Klebsiella pneumoniae clinical isolate is
      due to the combination of bla(ACT-1) beta-lactamase production, porin OmpK35/36
      insertional inactivation, and down-regulation of the phosphate transport porin
      phoe.
AB  - Clinical isolates of Klebsiella pneumoniae resistant to carbapenems and
      essentially all other antibiotics (multidrug resistant) are being isolated from
      some hospitals in New York City with increasing frequency. A highly related pair
      of K. pneumoniae strains isolated on the same day from one patient in a hospital
      in New York City were studied for antibiotic resistance. One (KP-2) was resistant
      to imipenem, meropenem, and sulopenem (MICs of 16 to 32 microg/ml) while the
      other (KP-1) was susceptible (MIC of 0.5 microg/ml); both contained the bla(ACT
      1), bla(SHV-1), and bla(TEM-1) beta-lactamases. bla(ACT-1) in both strains was
      encoded on a large approximately 150-kb plasmid. Both isolates contained an
      identical class 1 integron encoding resistance to aminoglycosides and
      chloramphenicol. They each had identical insertions in ompK35 and ompK36,
      resulting in disruption of these key porin genes. The carbapenem-resistant and 
      susceptible isolates were extensively studied for differences in the structural
      and regulatory genes for the operons acrRAB, marORAB, romA-ramA, soxRS, micF,
      micC, phoE, phoBR, rpoS, and hfq. No changes were detected between the isolates
      except for a significant down-regulation of ompK37, phoB, and phoE in KP-2 as
      deduced from reverse transcription-PCR analysis of mRNA and polyacrylamide gel
      electrophoresis separation of outer membrane proteins. Backcross analysis was
      conducted using the wild-type phoE gene cloned into the vector pGEM under
      regulation of its native promoter as well as the lacZ promoter following
      transformation into the resistant KP-2 isolate. The wild-type gene reversed
      carbapenem resistance only when under control of the heterologous lacZ promoter.
      In the background of ompK35-ompK36 gene disruption, the up-regulation of phoE in
      KP-1 apparently compensated for porin loss and conferred carbapenem
      susceptibility. Down-regulation of phoE in KP-2 may represent the normal state of
      this gene, or it may have been selected from KP-1 in vivo under antibiotic
      pressure, generating the carbapenem-resistant clone. This is the first study in
      the Enterobacteriaceae where expression of the phosphate-regulated PhoE porin has
      been associated with resistance to antimicrobials. Our results with this pair of
      Klebsiella clinical isolates highlight the complex and evolving nature of
      multiple drug resistance in this species.

PMID- 17005823
TI  - Development of a human immunodeficiency virus vector-based, single-cycle assay
      for evaluation of anti-integrase compounds.
AB  - Therapeutic strategies aimed at inhibiting human immunodeficiency virus type 1
      (HIV-1) replication employ a combination of drugs targeted to two viral enzymes
      (reverse transcriptase and protease) and to the viral entry/fusion step. However,
      the high propensity of HIV-1 to develop resistance makes the development of novel
      compounds targeting different steps of the HIV-1 life cycle essential. Among
      these, integrase (IN) inhibitors have successfully passed the early phases of
      clinical development. By preventing integration, IN inhibitors preclude viral
      replication while allowing production of extrachromosomal forms of viral DNA (E
      DNA). Here, we describe an improved and standardized assay aimed at evaluating IN
      inhibitors by taking advantage of the transcriptional activity of E-DNA produced
      by HIV-derived vectors in the absence of replication-competent virus. In this
      context, the use of the firefly luciferase gene as a reporter gene provides a
      rapid and quantitative measure of viral-vector infectivity, thus making it a safe
      and cost-effective assay for evaluating novel IN inhibitors.

PMID- 17005824
TI  - Compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid
      formulations.
AB  - We investigated the compartmentalized intrapulmonary pharmacokinetics of
      amphotericin B and its lipid formulations in healthy rabbits. Cohorts of three to
      seven noninfected, catheterized rabbits received 1 mg of amphotericin B
      deoxycholate (DAMB) per kg of body weight or 5 mg of either amphotericin B
      colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), or liposomal
      amphotericin B (LAMB) per kg once daily for a total of 8 days. Following sparse
      serial plasma sampling, rabbits were sacrificed 24 h after the last dose, and
      epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAM), and lung
      tissue were obtained. Pharmacokinetic parameters in plasma were derived by model
      independent techniques, and concentrations in ELF and PAM were calculated based
      on the urea dilution method and macrophage cell volume, respectively. Mean
      amphotericin B concentrations +/- standard deviations (SD) in lung tissue and PAM
      were highest in ABLC-treated animals, exceeding concurrent plasma levels by 70-
      and 375-fold, respectively (in lung tissue, 16.24 +/- 1.62 versus 2.71 +/- 1.22,
      6.29 +/- 1.17, and 6.32 +/- 0.57 microg/g for DAMB-, ABCD-, and LAMB-treated
      animals, respectively [P = 0.0029]; in PAM, 89.1 +/- 37.0 versus 8.92 +/- 2.89,
      5.43 +/- 1.75, and 7.52 +/- 2.50 mug/ml for DAMB-, ABCD-, and LAMB-treated
      animals, respectively [P = 0.0246]). By comparison, drug concentrations in ELF
      were much lower than those achieved in lung tissue and PAM. Among the different
      cohorts, the highest ELF concentrations were found in LAMB-treated animals (2.28
      +/- 1.43 versus 0.44 +/- 0.13, 0.68 +/- 0.27, and 0.90 +/- 0.28 microg/ml in DAMB
      , ABCD-, and ABLC-treated animals, respectively [P = 0.0070]). In conclusion,
      amphotericin B and its lipid formulations displayed strikingly different patterns
      of disposition in lungs 24 h after dosing. Whereas the disposition of ABCD was
      overall not fundamentally different from that of DAMB, ABLC showed prominent
      accumulation in lung tissue and PAM, while LAMB achieved the highest
      concentrations in ELF.

PMID- 17005825
TI  - Role of VraSR in antibiotic resistance and antibiotic-induced stress response in
      Staphylococcus aureus.
AB  - Exposure of Staphylococcus aureus to cell wall inhibitors induces massive
      overexpression of a number of genes, provided that the VraSR two-component
      sensory regulatory system is intact. Inactivation of vraS blocks this
      transcriptional response and also causes a drastic reduction in the levels of
      resistance to beta-lactam antibiotics and vancomycin. We used an experimental
      system in which the essential cell wall synthesis gene of S. aureus, pbpB, was
      put under the control of an isopropyl-beta-d-thiogalactopyranoside-inducible
      promoter in order to induce reversible perturbations in cell wall synthesis
      without the use of any cell wall-active inhibitor. Changes in the level of
      transcription of pbpB were rapidly followed by parallel changes in the vraSR
      signal, and the abundance of the pbpB transcript was precisely mirrored by the
      abundance of the transcripts of vraSR and some additional genes that belong to
      the VraSR regulon. Beta-lactam resistance in S. aureus appears to involve a
      complex stress response in which VraSR performs the critical role of a sentinel
      system capable of sensing the perturbation of cell wall synthesis and allowing
      mobilization of genes that are essential for the generation of a highly resistant
      phenotype. One of the sites in cell wall synthesis "sensed" by the VraSR system
      appears to be a step catalyzed by PBP 2.

PMID- 17005826
TI  - Structure-activity relationships of Bacillus cereus and Bacillus anthracis
      dihydrofolate reductase: toward the identification of new potent drug leads.
AB  - New and improved therapeutics are needed for Bacillus anthracis, the etiological
      agent of anthrax. To date, antimicrobial agents have not been developed against
      the well-validated target dihydrofolate reductase (DHFR). In order to address
      whether DHFR inhibitors could have potential use as clinical agents against
      Bacillus, 27 compounds were screened against this enzyme from Bacillus cereus,
      which is identical to the enzyme from B. anthracis at the active site. Several
      2,4-diamino-5-deazapteridine compounds exhibit submicromolar 50% inhibitory
      concentrations (IC(50)s). Four of the inhibitors displaying potency in vitro were
      tested in vivo and showed a marked growth inhibition of B. cereus; the most
      potent of these has MIC(50) and minimum bactericidal concentrations at which 50%
      are killed of 1.6 mug/ml and 0.09 mug/ml, respectively. In order to illustrate
      structure-activity relationships for the classes of inhibitors tested, each of
      the 27 inhibitors was docked into homology models of the B. cereus and B.
      anthracis DHFR proteins, allowing the development of a rationale for the
      inhibition profiles. A combination of favorable interactions with the
      diaminopyrimidine and substituted phenyl rings explains the low IC(50) values of
      potent inhibitors; steric interactions explain higher IC(50) values. These
      experiments show that DHFR is a reasonable antimicrobial target for Bacillus
      anthracis and that there is a class of inhibitors that possess sufficient potency
      and antibacterial activity to suggest further development.

PMID- 17005827
TI  - Ribavirin antagonizes the in vitro anti-hepatitis C virus activity of 2'-C
      methylcytidine, the active component of valopicitabine.
AB  - Ribavirin antagonizes the in vitro anti-hepatitis C virus (HCV) activity of the
      pyrimidine nucleoside analogue 2'-C-methylcytidine, the active component of the
      experimental anti-HCV drug valopicitabine. In contrast, the combination of
      ribavirin with either the purine nucleoside analogue 2'-C-methyladenosine or the
      HCV protease inhibitor VX-950 resulted in an additive antiviral activity. These
      findings may have implications when planning clinical studies with
      valopicitabine.

PMID- 17005828
TI  - Enhanced antiscrapie effect using combination drug treatment.
AB  - Combination treatment with pentosan polysulfate and Fe(III)meso-tetra(4
      sulfonatophenyl)porphine in mice beginning 14 or 28 days after scrapie
      inoculation significantly increased survival times. This increase may be
      synergistic, implying that the compounds act cooperatively in vivo. Combination
      therapy may therefore be more effective for treatment of transmissible spongiform
      encephalopathies and other protein-misfolding diseases.

PMID- 17005829
TI  - Reactivity of (1-->3)-beta-d-glucan assay with commonly used intravenous
      antimicrobials.
AB  - Forty-four intravenous antimicrobials were tested for the presence of (1-->3)
      beta-d-glucan (BG). Colistin, ertapenem, cefazolin, trimethoprim
      sulfamethoxazole, cefotaxime, cefepime, and ampicillin-sulbactam tested positive
      for BG at reconstituted-vial concentrations but not when diluted to usual maximum
      plasma concentrations. False-positive BG assays may occur when some
      antimicrobials are administered; however, this needs to be confirmed.

PMID- 17005830
TI  - Weak mutators can drive the evolution of fluoroquinolone resistance in
      Escherichia coli.
AB  - Weak mutators are common among clinical isolates of Escherichia coli. We show
      that the relative mutation rate and the "evolvability of fluoroquinolone
      resistance" are related by a power law slope of 1.2 over 3 orders of magnitude.
      Thus, even weak mutators can drive the evolution of fluoroquinolone resistance
      under selection pressure.

PMID- 17005831
TI  - Redefining a structural variant of staphylococcal cassette chromosome mec, SCCmec
      type VI.
AB  - Previously we identified a SCCmec variant similar in size to type IV but with a
      new ccrAB allotype, allotype 4. We addressed the epidemiological relevance of
      this variant and found it among several strains belonging to the same clone. We
      propose to rename this structural variant SCCmec type VI.

PMID- 17005832
TI  - Method for regulated expression of single-copy efflux pump genes in a surrogate
      Pseudomonas aeruginosa strain: identification of the BpeEF-OprC chloramphenicol
      and trimethoprim efflux pump of Burkholderia pseudomallei 1026b.
AB  - Construction and integration of recombinant mini-Tn7 expression vectors into the
      chromosome of a surrogate, efflux-sensitized, and biosafe Pseudomonas aeruginosa
      host was validated as a generally applicable method for studies of
      uncharacterized bacterial efflux pumps. Using this method, the Burkholderia
      pseudomallei bpeEF-oprC operon was shown to encode a chloramphenicol and
      trimethoprim efflux pump.

PMID- 17005833
TI  - Efficacy of ambruticin analogs in a murine model of invasive pulmonary
      aspergillosis.
AB  - Ambruticins are a family of polyketides. The antifungal activity of an
      ambruticin, KOSN-2079, was tested in the mouse model of invasive aspergillosis.
      KOSN-2079 significantly reduced pulmonary fungal burdens and improved survival
      over that with the vehicle control. These results support the continued
      development of ambruticins as antifungal agents.

PMID- 17005834
TI  - Efficacy of ambruticin analogs in a murine model of coccidioidomycosis.
AB  - Ambruticin S, an antifungal cyclopropyl-pyran acid, showed curative effects
      against murine coccidioidal infection. Two analogs of this compound with greater
      in vitro potency were tested against lethal murine Coccidioides infection. Both
      improved the survival of mice over that of controls; one resulted in near
      sterilization of infection.

PMID- 17005835
TI  - Maribavir antagonizes the antiviral action of ganciclovir on human
      cytomegalovirus.
AB  - The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir antagonized the anti
      CMV effect of ganciclovir, increasing the ganciclovir 50% inhibitory
      concentration against a sensitive strain by up to 13-fold. Antiviral activities
      of foscarnet and cidofovir were unaffected by maribavir.

PMID- 17005836
TI  - In vitro susceptibility of Clostridium difficile clinical isolates from a multi
      institutional outbreak in Southern Quebec, Canada.
AB  - Clostridium difficile isolates from a 2004 outbreak in Quebec, Canada, were all
      found to be susceptible to metronidazole, vancomycin, rifampin, and meropenem but
      resistant to bacitracin, cefotaxime, ciprofloxacin, and levofloxacin, and most
      (>80%) were resistant to ceftriaxone, clarithromycin, gatifloxacin, and
      moxifloxacin. The predominant NAP1 isolates were susceptible to clindamycin,
      while the NAP2 isolates were resistant.

PMID- 17005837
TI  - Intrinsic macrolide resistance in rapidly growing mycobacteria.
AB  - This study reports the discovery of erm genes in seven species of rapidly growing
      mycobacteria (RGM): Mycobacterium boenickei, M. goodii, M. houstonense, M.
      mageritense, M. neworleansense, M. porcinum, and M. wolinskyi. This study further
      substantiates the role of erm genes in intrinsic macrolide resistance in RGM.

PMID- 17005838
TI  - Antimicrobial susceptibility among pathogens collected from hospitalized patients
      in the United States and in vitro activity of tigecycline, a new glycylcycline
      antimicrobial.
AB  - The activities of tigecycline and comparators against isolates collected from 76
      U.S. centers between January 2004 and September 2005 were assessed. Tigecycline
      MIC(90)s were < or =2 microg/ml for Klebsiella pneumoniae, Klebsiella oxytoca,
      Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Serratia
      marcescens, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus
      faecalis, Enterococcus faecium, and Streptococcus agalactiae.

PMID- 17005839
TI  - SME-3, a novel member of the Serratia marcescens SME family of carbapenem
      hydrolyzing beta-lactamases.
AB  - Imipenem-resistant Serratia marcescens isolates were cultured from a lung
      transplant patient given multiple antibiotics over several months. The strains
      expressed SME-3, a beta-lactamase of the rare SME carbapenem-hydrolyzing family.
      SME-3 differed from SME-1 by a single amino acid substitution of tyrosine for
      histidine at position 105, but the two beta-lactamases displayed similar
      hydrolytic profiles.

PMID- 17005840
TI  - Protein O-mannosyltransferase isoforms regulate biofilm formation in Candida
      albicans.
AB  - Five isoforms of protein mannosyltransferase (Pmt) O-mannosylate secretory
      proteins in Candida albicans. pmt mutants were differentially defective for
      biofilm formation on plastic in static and flow-through systems, and a Pmt
      inhibitor blocked early stages of biofilm formation. Conceptually, Pmt inhibition
      may prevent surface anchoring and biofilm-dependent resistance of fungal
      pathogens.

PMID- 17005841
TI  - Deletions of the endocytic components VPS28 and VPS32 in Candida albicans lead to
      echinocandin and azole hypersensitivity.
AB  - Vps28p and Vps32p act in both the endocytic and the pH signaling pathways in
      yeasts and are required for Candida albicans virulence. Here, we show that
      deletions of VPS28 and VPS32 increase the susceptibility of C. albicans to cell
      wall disruption agents, echinocandin and azole antifungal agents.

PMID- 17005842
TI  - In vitro susceptibility of breakthrough Candida bloodstream isolates correlates
      with daily and cumulative doses of fluconazole.
AB  - We determined MICs for 28 Candida isolates recovered from patients who developed
      breakthrough candidemia while receiving fluconazole. MICs correlated with daily
      and cumulative doses of fluconazole. Patients receiving > or =2,000 mg
      cumulatively or >200 mg daily were more likely to be infected with isolates that
      were not fluconazole susceptible.

PMID- 17005843
TI  - Phase I dose escalation study to evaluate the safety and pharmacokinetic profile
      of tefibazumab in subjects with end-stage renal disease requiring hemodialysis.
AB  - Two cohorts of four subjects requiring hemodialysis received tefibazumab (10 or
      20 mg/kg). The mean elimination half-life was between 17 and 18 days, the average
      volume of distribution was 7.3 liters, and the average clearance was 12 ml/h for
      both dose groups. At a dose of 20 mg/kg of body weight, plasma levels were 88
      microg/ml at 21 days.

PMID- 17005844
TI  - Standardization of an experimental murine model of invasive pulmonary
      aspergillosis.
AB  - Evaluating new therapeutic agents for invasive aspergillosis requires animal
      models that are reproducible among different laboratories. We therefore evaluated
      a murine model of aerosol infection in two independent laboratories and found a
      high level of both intra- and interlaboratory reproducibility of survival, fungal
      burden over time, and the efficacy of liposomal amphotericin B.

PMID- 17005845
TI  - linG, a new integron-associated gene cassette encoding a lincosamide
      nucleotidyltransferase.

PMID- 17005846
TI  - Multidrug-resistant Salmonella enterica serovar typhi isolates with high-level
      resistance to ciprofloxacin in Dhaka, Bangladesh.

PMID- 17005847
TI  - Reinventing the biomedical journal.

PMID- 17005848
TI  - Matrix metalloproteinase-2 facilitates wound healing events that promote
      functional recovery after spinal cord injury.
AB  - Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in
      both injury and repair mechanisms in the CNS. Pharmacological blockade of MMPs,
      limited to the first several days after spinal cord injury, improves locomotor
      recovery. This beneficial response is, however, lost when treatment is extended
      beyond the acutely injured cord to include wound healing and tissue remodeling.
      This suggests that some MMPs play a beneficial role in wound healing. To test
      this hypothesis, we investigated the role of MMP-2, which is actively expressed
      during wound healing, in white matter sparing and axonal plasticity, the
      formation of a glial scar, and locomotor recovery after spinal cord injury. MMP-2
      increased between 7 and 14 d after injury, where it was immunolocalized in
      reactive astrocytes bordering the lesion epicenter. There was reduced white
      matter sparing and fewer serotonergic fibers, caudal to the lesion in injured MMP
      2 null animals. MMP-2 deficiency also resulted in increased immunoreactivity to
      chondroitin sulfate proteoglycans and a more extensive astrocytic scar. Most
      importantly, locomotion in an open field, performance on a rotarod, and grid
      walking were significantly impaired in injured MMP-2 null mice. Our findings
      suggest that MMP-2 promotes functional recovery after injury by regulating the
      formation of a glial scar and white matter sparing and/or axonal plasticity.
      Thus, strategies exploiting MMPs as therapeutic targets must balance these
      beneficial effects during wound healing with their adverse interactions in the
      acutely injured spinal cord.

PMID- 17005849
TI  - Na+, Cl-, and pH dependence of the human choline transporter (hCHT) in Xenopus
      oocytes: the proton inactivation hypothesis of hCHT in synaptic vesicles.
AB  - The recent cloning of the human choline transporter (hCHT) has allowed its
      expression in Xenopus laevis oocytes and the simultaneous measurement of choline
      transport and choline-induced current under voltage clamp. hCHT currents and
      choline transport are evident in cRNA-injected oocytes and significantly enhanced
      by the hCHT trafficking mutant L530A/V531A. The charge/choline ratio of hCHT
      varies from 10e/choline at -80 mV to 3e/choline at -20 mV, in contrast with the
      reported fixed stoichiometry of the Na+-coupled glucose transporter in the same
      gene family. Ion substitution shows that the choline uptake and choline-induced
      current are Na+ and Cl- dependent; however, the reversal potential of the induced
      current suggests a Na+-selective mechanism, consigning Cl- to a regulatory role
      rather than a coupled, cotransported-ion role. The hCHT-specific inhibitor
      hemicholinium-3 (HC-3) blocks choline uptake and choline-induced current; in
      addition, HC-3 alone reveals a constitutive, depolarizing leak current through
      hCHT. We show that external protons reduce hCHT current, transport, and binding
      with a similar pKa of 7.4, suggesting proton titration of residue(s) that support
      choline binding and transport. Given the localization of the choline transporter
      to synaptic vesicles, we propose that proton inactivation of hCHT prevents
      acetylcholine and proton leakage from the acidic interior of cholinergic synaptic
      vesicles. This mechanism would allow cholinergic, activity-triggered delivery of
      silent choline transporters to the plasma membrane, in which normal pH would
      reactivate the transporters for choline uptake and subsequent acetylcholine
      synthesis.

PMID- 17005850
TI  - Locus ceruleus regulates sensory encoding by neurons and networks in waking
      animals.
AB  - Substantial evidence indicates that the locus ceruleus (LC)-norepinephrine (NE)
      projection system regulates behavioral state and state-dependent processing of
      sensory information. Tonic LC discharge (0.1-5.0 Hz) is correlated with levels of
      arousal and demonstrates an optimal firing rate during good performance in a
      sustained attention task. In addition, studies have shown that locally applied NE
      or LC stimulation can modulate the responsiveness of neurons, including those in
      the thalamus, to nonmonoaminergic synaptic inputs. Many recent investigations
      further indicate that within sensory relay circuits of the thalamus both general
      and specific features of sensory information are represented within the
      collective firing patterns of like-modality neurons. However, no studies have
      examined the impact of NE or LC output on the discharge properties of ensembles
      of functionally related cells in intact, conscious animals. Here, we provide
      evidence linking LC neuronal discharge and NE efflux with LC-mediated modulation
      of single-neuron and neuronal ensemble representations of sensory stimuli in the
      ventral posteriomedial thalamus of waking rats. As such, the current study
      provides evidence that output from the LC across a physiologic range modulates
      single thalamic neuron responsiveness to synaptic input and representation of
      sensory information across ensembles of thalamic neurons in a manner that is
      consistent with the well documented actions of LC output on cognition.

PMID- 17005851
TI  - Oculomotor instabilities in zebrafish mutant belladonna: a behavioral model for
      congenital nystagmus caused by axonal misrouting.
AB  - A large fraction of homozygous zebrafish mutant belladonna (bel) larvae display a
      reversed optokinetic response (OKR) that correlates with failure of the retinal
      ganglion cells to cross the midline and form the optic chiasm. Some of these
      achiasmatic mutants display strong spontaneous eye oscillations (SOs) in the
      absence of motion in the surround. The presentation of a stationary grating was
      necessary and sufficient to evoke SO. Both OKR reversal and SO depend on vision
      and are contrast sensitive. We built a quantitative model derived from bel fwd
      (forward) eye behaviors. To mimic the achiasmatic condition, we reversed the sign
      of the retinal slip velocity in the model, thereby successfully reproducing both
      reversed OKR and SO. On the basis of the OKR data, and with the support of the
      quantitative model, we hypothesize that the reversed OKR and the SO can be
      completely attributed to RGC misrouting. The strong resemblance between the SO
      and congenital nystagmus (CN) seen in humans with defective retinotectal
      projections implies that CN, of so far unknown etiology, may be directly caused
      by a projection defect.

PMID- 17005853
TI  - Discrimination between the enantiomers of carvone and of terpinen-4-ol odorants
      in normal rats and those with lesions of the olfactory bulbs.
AB  - We assessed (1) whether the enantiomers of terpinen-4-ol, odorants that activate
      nearly identical areas of the olfactory bulb, are more difficult to discriminate
      than those of carvone, odorants that activate different areas of the olfactory
      bulb, and (2) whether olfactory bulb lesions that disrupt the pattern of bulbar
      activation produced by these enantiomers degraded the ability of rats to
      discriminate between them. In psychophysical tests, normal rats discriminated
      between the enantiomers of terpinen-4-ol and of carvone equally well. Surgical
      lesions that removed the majority of bulbar glomeruli activated by these odorants
      (as demonstrated in previous olfactory bulb studies using intrinsic optical
      imaging and 2-deoxyglucose) resulted in increased detection thresholds but few or
      no deficits in discriminating between suprathreshold concentrations of the
      enantiomers. These results fail to confirm predictions based on 2-deoxyglucose
      maps of bulbar activity that enantiomers of terpinen-4-ol should be more
      difficult to discriminate than those of carvone and that the ability to
      discriminate between enantiomers of an odorant are based on differences in
      patterns of bulbar activation revealed in such maps.

PMID- 17005852
TI  - Identification of a novel oligodendrocyte cell adhesion protein using gene
      expression profiling.
AB  - Oligodendrocytes undergo extensive changes as they differentiate from progenitors
      into myelinating cells. To better understand the molecular mechanisms underlying
      this transformation, we performed a comparative analysis using gene expression
      profiling of A2B5+ oligodendrocyte progenitors and O4+ oligodendrocytes. Cells
      were sort-purified ex vivo from postnatal rat brain using flow cytometry. Using
      Affymetrix microarrays, 1707 transcripts were identified with a more than twofold
      increase in expression in O4+ oligodendrocytes. Many genes required for
      oligodendrocyte differentiation were upregulated in O4+ oligodendrocytes,
      including numerous genes encoding myelin proteins. Transcriptional changes
      included genes required for cell adhesion, actin cytoskeleton regulation, and
      fatty acid and cholesterol biosynthesis. At the O4+ stage, there was an increase
      in expression of a novel proline-rich transmembrane protein (Prmp). Localized to
      the plasma membrane, Prmp displays adhesive properties that may be important for
      linking the extracellular matrix to the actin cytoskeleton. Together, our results
      highlight the usefulness of this discovery-driven experimental strategy to
      identify genes relevant to oligodendrocyte differentiation and myelination.

PMID- 17005854
TI  - Beta-arrestin2-mediated internalization of mammalian odorant receptors.
AB  - Odorant receptors comprise the biggest subfamily of G-protein-coupled receptors.
      Although the endocytic mechanisms of other G-protein-coupled receptors have been
      characterized extensively, almost nothing is known about the intracellular
      trafficking of odorant receptors. The present study describes the endocytic
      pathway of mammalian odorant receptors, which bind beta-arrestin2 with high
      affinity and are internalized via a clathrin-dependent mechanism. After prolonged
      odorant exposure, receptors are not targeted to lysosomal degradation but
      accumulate in recycling endosomes. Odorant-induced odorant receptor
      desensitization is promoted by cAMP-dependent protein kinase A phosphorylation
      and is dependent on serine and threonine residues within the third intracellular
      loop of the receptor. Moreover, beta-arrestin2 is redistributed into the
      dendritic knobs of mouse olfactory receptor neurons after treatment with a
      complex odorant mixture. Prolonged odorant exposure resulted in accumulation of
      beta-arrestin2 in intracellular vesicles. Adaptation of olfactory receptor
      neurons to odorants can be abolished by the inhibition of clathrin-mediated
      endocytosis, showing the physiological relevance of the here described mechanism
      of odorant receptor desensitization. A better understanding of odorant receptor
      trafficking and additional insight into the molecular determinants underlying the
      interactions of odorant receptors with beta-arrestin2 and other trafficking
      proteins will therefore be important to fully understand the mechanisms of
      adaptation and sensitization in the olfactory epithelium.

PMID- 17005855
TI  - GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and
      processing.
AB  - The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta
      site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta
      peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member
      of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family,
      interacts with BACE and influences its subcellular distribution. We now report
      that overexpression of GGA1 in cells increased the APP C-terminal fragment
      resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to
      the Golgi, in which fluorescence resonance energy transfer analyses suggest that
      the proteins come into close proximity. GGA1 blunted only APP but not notch
      intracellular domain release. These results suggest that GGA1 prevented APP beta
      cleavage products from becoming substrates for gamma-secretase. Direct binding of
      GGA1 to BACE was not required for these effects, but the integrity of the GAT
      (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch
      influencing APP trafficking and processing, so that APP-GGA1 interactions may
      have pathophysiological relevance in AD.

PMID- 17005856
TI  - Synaptic currents in anatomically identified CA3 neurons during hippocampal gamma
      oscillations in vitro.
AB  - Gamma-frequency oscillations are prominent during active network states in the
      hippocampus. An intrahippocampal gamma generator has been identified in the CA3
      region. To better understand the synaptic mechanisms involved in gamma
      oscillogenesis, we recorded action potentials and synaptic currents in distinct
      types of anatomically identified CA3 neurons during carbachol-induced (20-25
      microM) gamma oscillations in rat hippocampal slices. We wanted to compare and
      contrast the relationship between excitatory and inhibitory postsynaptic currents
      in pyramidal cells and perisomatic-targeting interneurons, cell types implicated
      in gamma oscillogenesis, as well as in other interneuron subtypes, and to relate
      synaptic currents to the firing properties of the cells. We found that phasic
      synaptic input differed between cell classes. Most strikingly, the dominant
      phasic input to pyramidal neurons was inhibitory, whereas phase-coupled
      perisomatic-targeting interneurons often received a strong phasic excitatory
      input. Differences in synaptic input could account for some of the differences in
      firing rate, action potential phase precision, and mean action potential phase
      angle, both between individual cells and between cell types. There was a strong
      positive correlation between the ratio of phasic synaptic excitation to
      inhibition and firing rate over all neurons and between the phase precision of
      excitation and action potentials in interneurons. Moreover, mean action potential
      phase angle correlated with the phase of the peak of the net-estimated synaptic
      reversal potential in all phase-coupled neurons. The data support a recurrent
      mechanism of gamma oscillations, whereby spike timing is controlled primarily by
      inhibition in pyramidal cells and by excitation in interneurons.

PMID- 17005857
TI  - Local interneurons regulate synaptic strength by retrograde release of
      endocannabinoids.
AB  - Neurons release endocannabinoids from their dendrites to trigger changes in the
      probability of transmitter release. Although such retrograde signaling has been
      described for principal neurons, such as hippocampal pyramidal cells and
      cerebellar Purkinje cells (PCs), it has not been demonstrated for local
      interneurons. Here we tested whether inhibitory interneurons in the cerebellum,
      stellate cells (SCs) and basket cells, regulate the strength of parallel fiber
      (PF) synapses by releasing endocannabinoids. We found that depolarization-induced
      suppression of excitation (DSE) is present in both SCs and basket cells. The
      properties of retrograde inhibition were examined more thoroughly for SCs. Both
      DSE and synaptically evoked suppression of excitation (SSE) triggered with brief
      PF bursts require elevations of postsynaptic calcium, are blocked by a type 1
      cannabinoid receptor (CB1R) antagonist, and are absent in mice lacking the CB1R.
      SSE for SCs is similar to that described previously for PCs in that it is
      prevented by BAPTA and DAG lipase inhibitors in the recording pipette; however,
      unlike in PCs, NMDA receptors (NMDARs) play an important role in SSE for SCs.
      Although SCs express CB1Rs postsynaptically, neither high-frequency firing of SCs
      nor PF bursts lead to autocrine suppression of subsequent SC activity. Instead,
      PF bursts decrease the amplitude of disynaptic inhibition in PCs by evoking
      endocannabinoid release that transiently reduces the ability of PF synapses to
      trigger spikes in SCs. Thus, local interneurons within the cerebellum can release
      endocannabinoids through metabotropic glutamate receptor- and NMDAR-dependent
      mechanisms and contribute to use-dependent modulation of circuit properties.

PMID- 17005858
TI  - Vestibular hair bundles control pH with (Na+, K+)/H+ exchangers NHE6 and NHE9.
AB  - In hair cells of the inner ear, robust Ca2+/H+ exchange mediated by plasma
      membrane Ca2+-ATPase would rapidly acidify mechanically sensitive hair bundles
      without efficient removal of H+. We found that, whereas the basolateral membrane
      of vestibular hair cells from the frog saccule extrudes H+ via an Na+-dependent
      mechanism, bundles rapidly remove H+ in the absence of Na+ and HCO3(-), even when
      the soma is acidified. K+ was fully effective and sufficient for H+ removal; in
      contrast, Rb+ failed to support pH recovery. Na+/H+-exchanger isoform 1 (NHE1)
      was present on hair-cell soma membranes and was likely responsible for Na+
      dependent H+ extrusion. NHE6 and NHE9 are organellar isoforms that can appear
      transiently on plasma membranes and have been proposed to mediate K+/H+ exchange.
      We identified NHE6 in a subset of hair bundles; NHE9 was present in all bundles.
      Heterologous expression of these isoforms in yeast strains lacking endogenous
      exchangers conferred pH-dependent tolerance to high levels of KCl and NaCl. NHE9
      preferred cations in the order K+, Na+ >> Rb+, consistent with the relative
      efficacies of these ions in promoting pH recovery in hair bundles. Electroneutral
      K+/H+ exchange, which we propose is performed by NHE9 in hair bundles, exploits
      the high-K+ endolymph, responds only to pH imbalance across the bundle membrane,
      is unaffected by the +80 mV endocochlear potential, and uses mechanisms already
      present in the ear for K+ recycling. This mechanism allows the hair cell to
      remove H+ generated by Ca2+ pumping without ATP hydrolysis in the cell.

PMID- 17005859
TI  - Global transcriptome analysis of genetically identified neurons in the adult
      cortex.
AB  - The enormous cellular complexity of the brain is a major obstacle for gene
      expression profiling of neurological disease models, because physiologically
      relevant changes of transcription in a specific neuronal subset are likely to be
      lost in the presence of other neurons and glia. We solved this problem in
      transgenic mice by labeling genetically defined cells with a nuclear variant of
      GFP. When combined with laser-directed microdissection, intact RNA from unfixed,
      freeze-dried sections can be isolated, which is a prerequisite for high-quality
      global transcriptome analysis. Here, we compared gene expression profiles between
      pyramidal motor neurons and pyramidal somatosensory neurons captured from layer V
      of the adult neocortex. One striking feature of motor neurons is the elevated
      expression of ribosomal genes and genes involved in ATP synthesis. This suggests
      a molecular adaptation of the upper motor neurons to longer axonal projections
      and higher electrical activity. These molecular signatures were not detected when
      cortical layers and microareas were analyzed in toto. Additionally, we used
      microarrays to determine the global mRNA expression profiles of microdissected
      Purkinje cells and cellularly complex cerebellar cortex microregions. In summary,
      our analysis shows that cellularly complex targets lead to averaged gene
      expression profiles that lack substantial amounts of cell type-specific
      information. Thus, cell type-restricted sampling strategies are mandatory in the
      CNS. The combined use of a genetic label with laser-microdissection offers an
      unbiased approach to map patterns of gene expression onto practically any cell
      type of the brain.

PMID- 17005860
TI  - Activation of group II metabotropic glutamate receptors attenuates both stress
      and cue-induced ethanol-seeking and modulates c-fos expression in the hippocampus
      and amygdala.
AB  - Major precipitating factors for relapse to drug use are stress and exposure to
      drug-related environmental stimuli. Group II (mGlu(2/3)) metabotropic glutamate
      receptors (mGluRs) are densely expressed within circuitries mediating the
      motivating effects of stress and drug cues and, therefore, may participate in
      regulating drug-seeking linked to both of these risk factors. Thus, we tested the
      hypothesis that pharmacological activation of group II mGluRs modifies both
      stress- and cue-induced ethanol-seeking, using reinstatement models of relapse.
      In parallel, brain c-fos expression was examined to identify neural substrates
      for the behavioral effects of group II mGluR activation. The selective mGlu(2/3)
      agonist LY379268 (1R,4R,5S,6R-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6
      dicarboxylate) (0.3, 1.0, and 3.0 mg/kg, s.c.) dose dependently blocked the
      recovery of extinguished ethanol-seeking induced by either footshock stress or
      ethanol-associated discriminative stimuli. These effects were accompanied by
      modulation of c-fos expression in the hippocampus, central nucleus of the
      amygdala, bed nucleus of the stria terminalis, and medial parvocellular
      paraventricular nucleus of the hypothalamus. The results implicate group II
      mGluRs as a shared neuropharmacological substrate for ethanol-seeking elicited by
      both drug cues and stress and identify group II mGluRs as promising treatment
      targets for relapse prevention.

PMID- 17005861
TI  - Targeted deletion of a single Sca8 ataxia locus allele in mice causes abnormal
      gait, progressive loss of motor coordination, and Purkinje cell dendritic
      deficits.
AB  - Spinocerebellar ataxia type 8 (SCA8) patients typically have a slowly
      progressive, adult-onset ataxia. SCA8 is dominantly inherited and is caused by
      large CTG repeat expansions in the untranslated antisense RNA of the Kelch-like 1
      gene (KLHL1), but the molecular mechanism through which this expansion leads to
      disease is still unknown. To more fully characterize the underlying molecular
      mechanisms involved in SCA8, we developed a mouse model in which Klhl1 is deleted
      in either all tissues or is deleted specifically in Purkinje cells only. We found
      that mice that are either homozygous or heterozygous for the Klhl1 deletion have
      significant gait abnormalities at an early age and develop a significant loss of
      motor coordination by 24 weeks of age. This loss progresses more rapidly in
      homozygous knock-outs. Mice with Klhl1 specifically deleted in only Purkinje
      cells had a loss of motor coordination that was almost identical to the total
      tissue deletion mice. Finally, we found significant Purkinje cell dendritic
      deficits, as measured by the thickness of the molecular layer, in all mice in
      which Klhl1 was deleted (both total and Purkinje cell-specific deletions) and an
      intermediate reduction in molecular layer thickness in mice with reduced levels
      of Klhl1 expression (heterozygous deletions). The results from this mouse model
      show that even a partial loss of Klhl1 function leads to degeneration of Purkinje
      cell function and indicates that loss of KLHL1 activity is likely to play a
      significant part in the underlying pathophysiology of SCA8.

PMID- 17005863
TI  - RTP801 is elevated in Parkinson brain substantia nigral neurons and mediates
      death in cellular models of Parkinson's disease by a mechanism involving
      mammalian target of rapamycin inactivation.
AB  - The molecules underlying neuron loss in Parkinson's disease (PD) are essentially
      unknown, and current therapies focus on diminishing symptoms rather than
      preventing neuron death. We identified RTP801 as a gene whose transcripts were
      highly induced in a cellular model of PD in which death of neuronal
      catecholaminergic PC12 cells was triggered by the PD mimetic 6-OHDA. Here, we
      find that RTP801 protein is also induced in this and additional cellular and
      animal PD models. To assess the relevance of these observations to PD, we used
      immunohistochemistry to compare RTP801 expression in postmortem brains from PD
      and control patients. For all PD brains examined, expression was highly elevated
      within neuromelanin-containing neurons of the substantia nigra but not in
      cerebellar neurons. Evaluation of the potential role of RTP801 induction in our
      cellular model revealed that RTP801 overexpression is sufficient to promote death
      but does not further elevate death caused by 6-OHDA. Furthermore, RTP801
      induction is requisite for death in our cellular PD models and in 6-OHDA-treated
      cultured sympathetic neurons in that its knockdown by short hairpin RNAs (shRNAs)
      is protective. The mechanism by which 6-OHDA and RTP801 induce neuron death
      appears to involve repression of mammalian target of rapamycin (mTOR) kinase
      activity, and such death is inhibited by shRNAs targeting TSC2 (tuberous
      sclerosis complex), a protein with which RTP801 interacts to block mTOR
      activation. Our findings thus suggest that the elevation of RTP801 we detect in
      PD substantia nigral neurons may mediate their degeneration and death and that
      RTP801 and its signaling cascade may be novel potential therapeutic targets for
      the disease.

PMID- 17005862
TI  - Modulation of Gq-protein-coupled inositol trisphosphate and Ca2+ signaling by the
      membrane potential.
AB  - Gq-protein-coupled receptors (GqPCRs) are widely distributed in the CNS and play
      fundamental roles in a variety of neuronal processes. Their activation results in
      phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis and Ca2+ release from
      intracellular stores via the phospholipase C (PLC)-inositol 1,4,5-trisphosphate
      (IP3) signaling pathway. Because early GqPCR signaling events occur at the plasma
      membrane of neurons, they might be influenced by changes in membrane potential.
      In this study, we use combined patch-clamp and imaging methods to investigate
      whether membrane potential changes can modulate GqPCR signaling in neurons. Our
      results demonstrate that GqPCR signaling in the human neuronal cell line SH-SY5Y
      and in rat cerebellar granule neurons is directly sensitive to changes in
      membrane potential, even in the absence of extracellular Ca2+. Depolarization has
      a bidirectional effect on GqPCR signaling, potentiating thapsigargin-sensitive
      Ca2+ responses to muscarinic receptor activation but attenuating those mediated
      by bradykinin receptors. The depolarization-evoked potentiation of the muscarinic
      signaling is graded, bipolar, non-inactivating, and with no apparent upper limit,
      ruling out traditional voltage-gated ion channels as the primary voltage sensors.
      Flash photolysis of caged IP3/GPIP2 (glycerophosphoryl-myo-inositol 4,5
      bisphosphate) places the voltage sensor before the level of the Ca2+ store, and
      measurements using the fluorescent bioprobe eGFP-PH(PLCdelta) (enhanced green
      fluorescent protein-pleckstrin homology domain-PLCdelta) directly demonstrate
      that voltage affects muscarinic signaling at the level of the IP3 production
      pathway. The sensitivity of GqPCR IP3 signaling in neurons to voltage itself may
      represent a fundamental mechanism by which ionotropic signals can shape
      metabotropic receptor activity in neurons and influence processes such as
      synaptic plasticity in which the detection of coincident signals is crucial.

PMID- 17005864
TI  - Alpha-internexin is structurally and functionally associated with the
      neurofilament triplet proteins in the mature CNS.
AB  - Alpha-internexin, a neuronal intermediate filament protein implicated in
      neurodegenerative disease, coexists with the neurofilament (NF) triplet proteins
      (NF-L, NF-M, and NF-H) but has an unknown function. The earlier peak expression
      of alpha-internexin than the triplet during brain development and its ability to
      form homopolymers, unlike the triplet, which are obligate heteropolymers, have
      supported a widely held view that alpha-internexin and neurofilament triplet form
      separate filament systems. Here, we demonstrate, however, that despite a
      postnatal decline in expression, alpha-internexin is as abundant as the triplet
      in the adult CNS and exists in a relatively fixed stoichiometry with these
      subunits. Alpha-internexin exhibits transport and turnover rates identical to
      those of triplet proteins in optic axons and colocalizes with NF-M on single
      neurofilaments by immunogold electron microscopy. Alpha-internexin also
      coassembles with all three neurofilament proteins into a single network of
      filaments in quadruple-transfected SW13vim(-) cells. Genetically deleting NF-M
      alone or together with NF-H in mice dramatically reduces alpha-internexin
      transport and content in axons throughout the CNS. Moreover, deleting alpha
      internexin potentiates the effects of NF-M deletion on NF-H and NF-L transport.
      Finally, overexpressing a NF-H-LacZ fusion protein in mice induces alpha
      internexin and neurofilament triplet to aggregate in neuronal perikarya and
      greatly reduces their transport and content selectively in axons. Our data show
      that alpha-internexin and the neurofilament proteins are functionally
      interdependent. The results strongly support the view that alpha-internexin is a
      fourth subunit of neurofilaments in the adult CNS, providing a basis for its
      close relationship with neurofilaments in CNS diseases associated with
      neurofilament accumulation.

PMID- 17005865
TI  - Role of megakaryoblastic acute leukemia-1 in ERK1/2-dependent stimulation of
      serum response factor-driven transcription by BDNF or increased synaptic
      activity.
AB  - Serum response factor (SRF)-mediated transcription contributes to developmental
      and adult brain plasticity. Therefore, we investigated the role of a newly
      identified SRF coactivator, MKL1, in the regulation of SRF-driven transcription
      in rat forebrain neurons. MKL1 expression was found in newborn rat cortical or
      hippocampal neurons in culture as well as in adult rat forebrain. Immunostaining
      demonstrated constitutive nuclear localization of MKL1 in the CA1 region of the
      hippocampus, in the deep layers of the neocortex, and in cultured neurons.
      Overexpression of MKL1 in primary cortical neurons elevated SRF-driven
      transcription and enhanced its stimulation by BDNF. In addition, inhibition of
      endogenous MKL1 by overexpression of a dominant-negative MKL1 mutant or by small
      interfering RNA reduced BDNF activation of SRF-driven transcription. In neurons,
      endogenous MKL1 was associated with SRF-regulated chromatin regions of several
      endogenous genes including c-fos, JunB, Srf, and Cyr61. BDNF activation of
      MKL1/SRF-driven transcription was dependent on the extracellular signal-regulated
      kinase 1/2 (ERK1/2) pathway, which also led to MKL1 phosphorylation. Finally,
      synaptic activity stimulation of SRF-driven transcription was reduced by
      inhibition of endogenous MKL1. Conversely, synaptic activity enhanced
      transcription by overexpressed MKL1. MKL1 regulation by synaptic activity was
      mediated through the NMDA receptor-activated ERK1/2. These results suggest that
      neuronal MKL1 contributes to SRF-regulated gene expression induced by BDNF or
      synaptic activity. In addition, MKL1 appears as a novel mediator of the signaling
      between ERK1/2 and SRF. Moreover, MKL1 is a likely regulator of SRF-driven
      transcription programs that underlie neuronal plasticity.

PMID- 17005866
TI  - Interface interactions modulating desensitization of the kainate-selective
      ionotropic glutamate receptor subunit GluR6.
AB  - Ionotropic glutamate receptors from the AMPA and kainate subfamilies share many
      functional and structural features, but it is unclear whether this similarity
      extends to the molecular mechanisms underlying receptor desensitization. The
      current model for desensitization in AMPA receptors involves the rearrangement of
      dimers formed between subunit agonist binding domains. Key evidence for this has
      come from a single point mutant (from leucine to tyrosine) that abolished
      desensitization and that was shown to stabilize the binding domain dimer.
      However, the desensitization of kainate receptors appears to differ from that of
      AMPA receptors in several key respects. Although the kinetics of AMPA receptor
      gating and desensitization are consistent with channels formed from two dimers,
      similar evidence for the functional involvement of dimers has not been found in
      kainate receptors. Furthermore, despite the homolog of the nondesensitizing
      tyrosine in AMPA subunits also being a tyrosine in wild-type kainate subunits,
      these receptors desensitize rapidly and completely. Using mutagenesis based on
      the crystal structure of the glutamate receptor subunit GluR6 S1S2 domain in
      complex with domoate, we identified four residues neighboring this tyrosine that
      differ between AMPA and kainate subunits and that contribute to the different
      desensitization kinetics of these receptors. Detailed analysis of the effects of
      mutations at these sites confirms that there is in fact a common general
      mechanism for desensitization in non-NMDA receptors, dependent on the stability
      of the binding domain dimer interface, and reveals the existence of potential
      agonist-specific desensitization pathways.

PMID- 17005867
TI  - Bidirectional dopaminergic modulation of excitatory synaptic transmission in
      orexin neurons.
AB  - Orexin neurons in the lateral hypothalamus (LH)/perifornical area (PFA) are known
      to promote food intake as well as provide excitatory influence on the
      dopaminergic reward pathway. Dopamine (DA), in turn, inhibits the reward pathway
      and food intake through its action in the LH/PFA. However, the cellular mechanism
      by which DA modulates orexin neurons remains largely unknown. Therefore, we
      examined the effect of DA on the excitatory neurotransmission to orexin neurons.
      Whole-cell patch-clamp recordings were performed using acute rat hypothalamic
      slices, and orexin neurons were identified by their electrophysiological and
      immunohistochemical characteristics. Pharmacologically isolated action potential
      independent miniature EPSCs (mEPSCs) were monitored. Bath application of DA
      induced a bidirectional effect on the excitatory synaptic transmission dose
      dependently. A low dose of DA (1 microM) increased mEPSC frequency, which was
      blocked by the D1-like receptor antagonist SCH 23390, and mimicked by the D1-like
      receptor agonist SKF 81297. In contrast, higher doses of DA (10-100 microM)
      decreased mEPSC frequency, which could be blocked with the D2-like receptor
      antagonist, sulpiride. Quinpirole, the D2-like receptor agonist, also reduced
      mEPSC frequency. None of these compounds affected the mEPSCs amplitude,
      suggesting the locus of action was presynaptic. Furthermore, DA (1 microM)
      induced an increase in the action potential firing, whereas DA (100 microM)
      hyperpolarized and ceased the firing of orexin neurons, indicating the effect of
      DA on excitatory synaptic transmission may influence the activity of the
      postsynaptic cell. In conclusion, our results suggest that D1- and D2-like
      receptors have opposing effects on the excitatory presynaptic terminals impinging
      onto orexin neurons.

PMID- 17005868
TI  - Reconsolidation and extinction of conditioned fear: inhibition and potentiation.
AB  - NMDA receptors are important for the acquisition, reconsolidation, and extinction
      of memories. NMDA receptor antagonists impair these memory processes, whereas the
      partial agonist D-cycloserine (DCS) potentiates both learning and extinction.
      Here, we used DCS and the noncompetitive NMDA receptor antagonist (+)-5-methyl
      10,11-dihydro-SH-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) to
      investigate the effects of enhancing and blocking NMDA receptor-mediated
      glutamatergic transmission on the reconsolidation and extinction of a conditioned
      fear memory. Either long extinction training or short memory reactivation
      sessions were used to preferentially engage extinction and reconsolidation
      processes, respectively. MK-801 blocked extinction to maintain high levels of
      conditioned freezing, and DCS potentiated extinction to reduce freezing, when
      they were administered before a long extinction training session. However, the
      opposite behavioral outcome was observed when the brief memory reactivation
      session was used: MK-801 administration impaired, whereas DCS increased,
      freezing, likely reflecting impairment and enhancement of reconsolidation,
      respectively. Finally, by using localized intracerebral infusions, we showed that
      the basolateral amygdala is a primary locus of action of systemically
      administered DCS. Thus, intrabasolateral amygdala DCS potentiated both the
      extinction and the reconsolidation of fear conditioning, depending on the length
      of the extinction/memory reactivation session. Therefore, memory reconsolidation
      can be both disrupted and enhanced, and extinction can be both potentiated and
      impaired, either to reduce or increase conditioned fear. These results have
      important implications for the use of reconsolidation blockade and potentiation
      of extinction as treatment strategies for maladaptive memory disorders.

PMID- 17005869
TI  - Structural basis for map formation in the thalamocortical pathway of the
      barrelless mouse.
AB  - Barrelless mice (BRL) homozygous for the BRL mutation that disrupts the gene
      coding for adenylyl cyclase type I on chromosome 11 lack spatial segregation of
      layer IV cortical cells and of the thalamocortical axons (TCAs) into barrel
      domains. Despite these morphological perturbations, a functional topographic map
      has been demonstrated. We reconstructed individual biocytin-injected TCAs from
      thalamus to barrel cortex in NOR (normal) and BRL mice to analyze to what extent
      the TCA arborization pattern and bouton distribution could explain the
      topographic representation of the whisker follicles. In BRL, the geometry of TCA
      is modified within layer IV as well as in infragranular layers. However, in both
      strains, the spatial distribution of TCA in layer IV reflects the spatial
      relationship of their cell bodies in the ventrobasal nucleus of the thalamus. The
      morphometric analysis revealed that TCAs of both strains have the same length,
      branch number, and number of axonal boutons in layer IV. However, in barrelless,
      the boutons are distributed within a larger tangential extent. Analysis of the
      distribution of boutons from neighboring thalamic neurons demonstrated the
      existence in layer IV of domains of high bouton density that in both strains
      equal the size and shape of individual barrels. We propose that the domains of
      high bouton density are at the basis of the whisker map in barrelless mice.

PMID- 17005870
TI  - Cytosolic catechols inhibit alpha-synuclein aggregation and facilitate the
      formation of intracellular soluble oligomeric intermediates.
AB  - Aberrant aggregation of alpha-synuclein (alpha-syn) to form fibrils and insoluble
      aggregates has been implicated in the pathogenic processes of many
      neurodegenerative diseases. Despite the dramatic effects of dopamine in
      inhibiting the formation of alpha-syn fibrils by stabilization of oligomeric
      intermediates in cell-free systems, no studies have examined the effects of
      intracellular dopamine on alpha-syn aggregation. To study this process and its
      association with neurodegeneration, intracellular catechol levels were increased
      to various levels by expressing different forms of tyrosine hydroxylase, in cells
      induced to form alpha-syn aggregates. The increase in the steady-state dopamine
      levels inhibited the formation of alpha-syn aggregates and induced the formation
      of innocuous oligomeric intermediates. Analysis of transgenic mice expressing the
      disease-associated A53T mutant alpha-syn revealed the presence of oligomeric
      alpha-syn in nondegenerating dopaminergic neurons that do contain insoluble alpha
      syn. These data indicate that intraneuronal dopamine levels can be a major
      modulator of alpha-syn aggregation and inclusion formation, with important
      implications on the selective degeneration of these neurons in Parkinson's
      disease.

PMID- 17005871
TI  - Mycotic aortic aneurysm following treatment of pyogenic vertebral osteomyelitis.
AB  - Mycotic aortic aneurysm is a surgical emergency. However, its bizarre
      presentations could delay the golden hour of surgical reconstruction which is the
      mainstay of treatment. We report a case of mycotic aneurysm of the aortic arch
      which developed in the postoperative period after surgical treatment of pyogenic
      vertebral osteomyelitis at the lower thoracic level.

PMID- 17005872
TI  - Thoracoscopic findings of a small posterior mediastinal parathyroid adenoma.
AB  - We report herein the rare case of a posterior mediastinal parathyroid adenoma 8
      mm in diameter, that was identified by both 99m-technetium
      methoxyisobutylisonitrile scintigraphy (Tc-MIBI) and high-resolution chest
      computed tomography (HRCT). Thoracoscopy clearly showed a mediastinal parathyroid
      adenoma which was successfully removed.

PMID- 17005873
TI  - Surgical repair for entire inferior vena cava occlusion in Budd-Chiari syndrome.
AB  - Successful repair of thrombotic occlusion of the entire inferior vena cava,
      including the iliac and hepatic veins, was performed on a 51-year-old man with
      Budd-Chiari syndrome associated with severe liver dysfunction.

PMID- 17005874
TI  - Early failure of surgical angioplasty with tissue glue: a word of caution.
AB  - A 43-year-old woman with critical stenosis of the left main stem was managed with
      saphenous vein angioplasty using BioGlue. She developed severe myocardial
      ischemia postoperatively, probably due to external compression exerted on the
      patch by the adhesive material, and required emergency coronary artery bypass
      grafting.

PMID- 17005875
TI  - Successful in situ treatment of infected aortic arch prosthesis by omental
      wrapping.
AB  - A 67-year-old man who underwent total aortic arch graft replacement with coronary
      artery bypass grafting developed postoperative Serratia mediastinitis. Re
      operative debridement and irrigation were carried out. An infected aortic arch
      prosthesis was successfully treated by in situ disinfection followed by complete
      omental wrapping.

PMID- 17005876
TI  - A case of 24 years longevity of an Ionescu-Shiley bioprosthesis in the mitral
      position.
AB  - Valve dysfunction, attributed to primary tissue failure several years after
      implantation of Ionescu-Shiley bioprostheses, has led to re-operation in most
      cases. We report a rare case of this bioprosthesis showing stenosis and
      regurgitation after implantation in the mitral position 24 years previously. No
      cusp tears, but severe calcification and well-grown neointima over the Dacron
      cloth of the inner surface were observed. This may explain how the valve
      functioned for such a long period of time. We replaced it with a Carpentier
      Edwards pericardial bioprosthesis.

PMID- 17005877
TI  - Extension of pulmonary adenocarcinoma into the left atrium.
AB  - A 62-year-old man presented with pulmonary adenocarcinoma that penetrated through
      the pulmonary vein into the left atrium. The tumor in the left atrium was removed
      via a right lower lobectomy under cardiopulmonary bypass. In selected cases,
      radical removal of a tumor in patients without mediastinal lymph node involvement
      may improve the prognosis. The use of cardiopulmonary bypass extends the
      possibilities of radical tumor removal.

PMID- 17005878
TI  - Who reviews the reviewers?

PMID- 17005879
TI  - Desmoid tumors of the chest wall.
AB  - Chest wall desmoid tumors (DT) are rare pathologic entities with microscopic
      features similar to, or undistinguishable from, fibromas or fibrosarcomas. From
      1996 to 2001, four patients with DT were surgically managed in our department.
      Their ages ranged from 27 years to 43 years (mean 32.25 years, median 29.5
      years). A resection of the lesion was performed with negative margins of 4 cm
      around the tumor (wide resection). A reconstruction of the chest wall was also
      performed with polytetrafluoroethylene (PTFE) in 2 patients and
      methylmethacrolate with Marlex mesh in 1 patient. One patient had a recurrence 15
      months later, and was admitted for complementary resection, and remains disease
      free for 5 years. The rest 3 patients are disease-free for 6 months to 5 years.
      Resection must include all adjacent, overlying and underlying musculature as well
      as soft tissues and any spare skin from the procedure should be used. Prognosis
      after a wide resection is good.

PMID- 17005880
TI  - Role and outcome of surgery for pulmonary tuberculosis.
AB  - The need and outcome of surgical intervention in patients with pulmonary
      tuberculosis were assessed retrospectively. Between 1993 and 2003, 72 major
      surgical procedures were performed in 57 patients with pulmonary tuberculosis.
      There were 44 males and 13 females with a mean age of 34 years. Indications for
      surgery were: trapped lung in 18 (31.6%), multidrug-resistant tuberculosis in 10
      (17.5%), aspergilloma in 10 (17.5%), destroyed lung in 5 (8.8%), massive
      hemoptysis in 4 (7%), bronchopleural fistula in 3 (5.3%), persistent cavity in 2
      (3.5%), and undiagnosed nodule in 5 (8.8%) patients. The most common procedure
      was lobectomy (31.9%). Other procedures included decortication, wedge resection,
      pneumonectomy, segmentectomy, and myoplasty. There were 28 complications in 18
      patients, including prolonged air leak in 12 (21.1%), residual space in 7
      (12.3%), empyema in 5 (8.8%), hematoma in 2 (3.5%), chylothorax and
      bronchopleural fistula in 1 (1.8%) each. There was no operative death, but one
      patient died from sepsis late in the follow-up period (mortality, 1.8%). As
      morbidity and mortality rates are acceptable, surgical intervention can be
      considered safe and effective in patients with pulmonary tuberculosis.

PMID- 17005881
TI  - Outcome of single ventricle and total anomalous pulmonary venous connection.
AB  - Management of patients with single-ventricle physiology is significantly affected
      by anomalies of pulmonary venous return at all stages, whether primary
      palliation, bidirectional Glenn shunt, or completion of Fontan circulation. We
      treated 25 patients with pulmonary venous anomalies and single ventricle by
      staged palliation, from June 1996 to May 2005. Visceral heterotaxy with atrial
      isomerism was present in 19 of them. Primary palliation with a systemic-to
      pulmonary artery shunt was undertaken in 15 patients. There were 5 early deaths,
      of which 4 were due to obstruction of pulmonary venous return. A bidirectional
      Glenn shunt was constructed in 17 patients including 10 who had it as a primary
      palliative procedure. There were 7 early deaths after the bidirectional Glenn
      procedure; only one was due to pulmonary venous obstruction. Five patients
      attained completion of the Fontan procedure. There was one early death after the
      Fontan operation. Anomalous pulmonary venous return can significantly complicate
      the management of patients with single ventricle, with an impact on survival in
      early infancy. Palliation with the aim of instituting extracardiac conduit Fontan
      circulation allows greater latitude and more streamlined management.

PMID- 17005882
TI  - Mitral valve surgery for dilated cardiomyopathy with mitral regurgitation.
AB  - Outcomes of surgery for non-ischemic non-valvular dilated cardiomyopathy with
      associated mitral regurgitation were assessed in 8 consecutive patients who
      underwent 9 mitral valve operations between 2001 and 2004. Mitral valve
      replacement was performed when the coaptation depth exceeded 10 mm. Two patients
      initially underwent mitral valvuloplasty, and 6 underwent valve replacement. One
      patient had valve replacement soon after valvuloplasty. Transthoracic
      echocardiography was performed immediately before surgery, before discharge, and
      during follow-up. Transesophageal echocardiography was carried out
      intraoperatively to assess valvular and ventricular function. Postoperative mean
      functional class was significantly better than the preoperative value (2.4 +/-
      0.7 vs. 3.3 +/- 0.7), and the improvement was sustained during follow-up (2.0 +/-
      0.7). The ejection fraction and left ventricular end-diastolic dimension did not
      improve. One patient died without leaving hospital and two died during follow-up.
      The 2- and 4-year survival rates were 75.0% and 37.5%. Mitral valve surgery
      improved functional class without obvious changes in ejection fraction or left
      ventricular end-diastolic dimension.

PMID- 17005883
TI  - Classic Konno-Rastan procedure: indications and results in the current era.
AB  - Diffuse or unresectable subaortic stenosis is difficult to treat and needs
      aggressive resection to effectively relieve the obstruction. Anterior
      aortoventriculoplasty, known as the Konno-Rastan procedure, has been shown to
      effectively tackle the problems encountered in diffuse subaortic stenosis. A
      retrospective study was carried out on patients who had undergone a Konno-Rastan
      procedure at our institution from March 1997 to November 2003. There were 26
      patients (16 males and 10 females). The mean age at operation was 12.8 +/- 7
      years. The mean follow-up period was 30.4 +/- 14.5 months. Only mechanical valves
      were used in this group of patients. The overall 30-day mortality was 11.5% (3
      patients). The mean preoperative peak systolic gradient decreased significantly
      from 91.3 +/- 39.3 to 28.1 +/- 17.7 mm Hg. Four patients developed permanent
      complete heart block and 2 had a residual ventricular septal defect in late
      follow-up. The classic Konno-Rastan procedure using a mechanical valve can be
      performed with acceptable morbidity and mortality in this difficult group of
      patients.

PMID- 17005884
TI  - Mitral valve annuloplasty with Carpentier-Edwards physio ring: mid-term results.
AB  - The mid-term results of mitral valve repair with the Carpentier-Edwards Physio
      annuloplasty ring were assessed in 97 consecutive patients in a single tertiary
      referral cardiothoracic surgical center. The mean follow-up time was 3.9 years
      (range, 1 month to 8.9 years). Most patients were in functional class II and III
      before the operation. Ejection fraction was < 40% in 8 patients. Causes of mitral
      regurgitation included degenerative disease (66%), infective endocarditis
      (13.4%), rheumatic disease (10.3%), and ischemic heart disease (9.3%). Thirty-day
      mortality was 2.1%. Actuarial survival and freedom from re-operation at 8 years
      were 91% and 90.8%, respectively. The only significant risk factor for re
      operation was residual mitral regurgitation. Four patients suffered
      thromboembolic complications, giving an overall event-free survival of 93% +/-
      3.7% during the follow-up period. The Carpentier-Edwards Physio ring provides
      safe and effective repair of mitral regurgitation on mid-term follow-up.

PMID- 17005885
TI  - Evaluation of the spatial resolution with 1.5-4 tesla in a stenosis model.
AB  - Since it was first described in the early 1990s, magnetic resonance coronary
      angiography has evolved into a promising noninvasive modality for imaging the
      coronary arteries. The aim of this study was to evaluate the detection accuracy
      and spatial resolution of vascular stenosis in contrast-enhanced 3-dimensional
      magnetic resonance angiography on a flow phantom. The examinations were performed
      with 1.5, 3, and 4 T whole-body imaging systems. For imaging at 4 T, we used a
      gradient-echo-multi-slice sequence. The system was flushed with gadopentetate
      dimeglumine contrast medium at flow rates of 40 and 60 mL.min(-1). The accurate
      detection of in vitro stenoses was possible in segments of 0.4 mm in diameter at
      4 T. The best results were obtained at a flow velocity of 40 mL.min(-1) and a
      contrast medium concentration of 0.2 mmol.L(-1). Contrast-enhanced high-field 3
      dimensional magnetic resonance imaging provided a highly accurate evaluation of
      the degree of stenosis in this model. Exact evaluation of vessel diameters < 0.4
      mm was not possible, even with 4 T. In vivo studies are necessary to overcome the
      current limitations in the visualization of small distal vessel segments.

PMID- 17005886
TI  - Kinking of the atrioventricular plane during the cardiac cycle.
AB  - Systolic descent of the atrioventricular plane toward the relatively stationary
      left ventricular apex is well described. As the atrioventricular plane includes
      two separate valvular units, systolic atrioventricular plane displacement should
      not be homogenous. In 6 sheep, sonomicrometric crystals were implanted at the
      base of the right coronary sinus, anterolateral and posteromedial fibrous
      trigones, posterior mitral annulus, left ventricular apex, and the tips of the
      anterior and posterior mitral leaflets. The aortomitral angle was calculated and
      related to simultaneous left ventricular and aortic pressures and mitral valve
      movement. The aortomitral angle was largest at end diastole (150.73 degrees +/-
      15.48 degrees ). During isovolumic contraction, it narrowed rapidly to 144.90
      degrees +/- 16.64 degrees , followed by a slower narrowing during ejection until
      it reached its smallest angle at end systole (139.66 degrees +/- 16.78 degrees ).
      During isovolumic relaxation, the aortomitral angle increased to 143.66 degrees
      +/- 16.02 degrees at the beginning of diastole. During the first third of
      diastole, it narrowed again to 141 degrees +/- 16.24 degrees before re-expanding
      to maximum at end diastole. During systole, the atrioventricular plane descended
      non-homogeneously toward the apex, with kinking at the hinge between the aortic
      and mitral annulus plane. This deformation of the atrioventricular plane has
      relevance in valve surgery.

PMID- 17005887
TI  - Operative treatment of sternal fractures.
AB  - Four patients with displaced sternal fractures complained of intractable pain
      following road traffic accidents. They all had bone deformities, but only one had
      associated traumatic injuries. All patients underwent operative reduction and
      fixation of the fractured sternum using a T-shaped compression-tension stainless
      steel plate and screws. Pain relief was often dramatic and all patients
      progressed to sternal union. None required reoperation. No infections occurred.
      Two plates have subsequently been removed. On follow-up, all patients had
      excellent results. Sternal plating, which is based on the tension-band principle,
      is an effective treatment for displaced sternal fractures.

PMID- 17005888
TI  - Intrapulmonary channel for one-stage correction of aortic arch obstruction.
AB  - There are several methods of surgical repair of aortic coarctation or
      interruption; the optimal technique is still controversial. The purpose of this
      study was to assess a new surgical method: intrapulmonary channel for one-stage
      repair of aortic coarctation or interruption associated with intracardiac
      anomalies. Between 1993 and 1995, 4 patients with aortic coarctation or
      interruption and intracardiac anomalies received one-stage surgical correction.
      Their ages ranged from 5 to 26 years (mean, 16 years). The aortic arch lesions
      were preductal coarctation in 2, and type B interruption in 2. Coexisting
      anomalies consisted of patent ductus arteriosus in 4, ventricular septal defect
      in 3, and aortopulmonary window in 1. An intrapulmonary channel was constructed
      in all patients, and co-existing anomalies were corrected simultaneously. There
      was no hospital death or late mortality. A cerebral complication occurred in one
      patient because of air embolism. Mean follow-up was 9.5 years (range, 8.5-11.5
      years). There was no evidence of recoarctation or late aneurysm formation. For
      selected patients with aortic coarctation or interruption and intracardiac
      anomalies, an intrapulmonary channel might be an option for one-stage correction.

PMID- 17005889
TI  - Analysis of surgical treatment for pulmonary aspergilloma.
AB  - Surgery for pulmonary aspergilloma is reputed to be risky. The results of
      surgical treatment of pulmonary aspergilloma in 41 patients between 1988 and 2003
      were evaluated retrospectively. Hemoptysis occurred in 31 patients (75.6%) and it
      was massive (> 300 mL in 24 hr) in 3. The underlying lung disease was
      tuberculosis in 35, bullous lung disease in 2, hydatid cyst in 2, and lung
      carcinoma in 2 patients. Lobectomy, bilobectomy, wedge resection, and
      pneumonectomy were performed in 27, 4, 6, and 4 patients respectively. The
      postoperative complication rate was 24.4%. One patient, who had a right
      pneumonectomy, died due to respiratory failure; the mortality rate was 2.4%.
      Recurrent hemoptysis was observed in only one patient. Early surgical treatment
      of patients with pulmonary aspergilloma resulted in a satisfactory outcome with
      acceptable morbidity, low mortality, and effective prevention of recurrent
      hemoptysis. Pneumonectomy has a high morbidity, thus it should be avoided if
      possible.

PMID- 17005890
TI  - Thoracoscopic surgery for pulmonary arteriovenous malformation.
AB  - We report 6 consecutive cases of pulmonary arteriovenous malformation in the
      periphery of the lung, which were treated successfully by thoracoscopy. Pulmonary
      wedge resection was performed with a linear cutting stapler to divide the feeding
      artery, drainage vein, and aneurysmal lesion of the arteriovenous malformation.
      Operative time ranged from 30 to 95 min (mean, 50 min). Bleeding was minimal in
      all cases. No major surgery-related complications were observed. Postoperative
      hospital stay was limited to one week except for one patient who had experienced
      a brain infarction preoperatively, caused by migration of an embolization coil.
      Histological examination confirmed that the arteriovenous malformation foci were
      completely removed. Pulmonary wedge resection through thoracoscopy is feasible as
      an alternative treatment for arteriovenous malformation located in the periphery
      of the lung parenchyma when pulmonary embolization therapy is difficult or
      unsuccessful.

PMID- 17005891
TI  - Multinodular goiter compressing the trachea following open heart surgery.
AB  - Acute hemorrhage into an adenomatous goiter following cardiac surgery is a rare
      cause of acute upper airway obstruction. We report an unusual presentation of
      respiratory distress in a patient with goiter recovering from open heart surgery,
      which was successfully treated by left hemithyroidectomy. A mandatory evaluation
      of the upper trachea in patients with long-standing benign goiter is recommended
      prior to cardiac surgery.

PMID- 17005892
TI  - Treatment of right heart failure with a new microaxial blood pump.
AB  - Isolated postcardiotomy right ventricular failure is rare but associated with a
      high mortality. Therefore, new developments reducing this mortality are
      necessary. We report our first successful clinical use of a new paracardiac right
      ventricular microaxial blood pump which was developed for postcardiotomy right
      heart failure.

PMID- 17005893
TI  - Cardiac tamponade due to spontaneous rupture of large coronary artery aneurysm.
AB  - A 70-year-old woman admitted with chest pain went into shock due to cardiac
      tamponade; 1000 mL of blood was drained from her pericardium. Enhanced computed
      tomography showed massive pericardial effusion and a coronary artery aneurysm in
      front of the main pulmonary artery. Coronary angiography revealed a coronary
      artery-pulmonary artery fistula and 3 giant saccular coronary artery aneurysms.
      Emergency surgical repair was successful.

PMID- 17005894
TI  - Malignant peripheral nerve sheath tumor of the heart.
AB  - A 32-year-old man presented with dyspnea, chest pain, palpitations and ankle
      edema and was found to have a tumor involving the heart. This was diagnosed as
      malignant peripheral nerve sheath tumor, a rare sarcoma of the heart.
      Immunohistochemistry was utilized to establish the diagnosis. The details of the
      patient's clinical course, and imaging findings with morphological and
      immunohistochemistry data are reported.

PMID- 17005895
TI  - Pacing in preterm with hydrops fetalis due to congenital complete heart block.
AB  - Hydrops fetalis due to congenital complete heart block (CCHB) is a rare
      condition. The outcome of the preterm fetus with hydrops fetalis due to CCHB is
      poor, and is frequently associated with significant morbidity and mortality. The
      management of this condition is difficult. We report our experience in a hydropic
      preterm using staged pacing by applying left ventricular epicardial pacing with a
      temporary pacemaker and subsequently, left ventricular epicardial pacing with a
      permanent pacemaker.

PMID- 17005896
TI  - Longitudinal reinforcement for treatment of sternal dehiscence.
AB  - Re-fixation of the sternum after sternal dehiscence is still a problem following
      cardiac surgery. An original technique that allows reinforcement against various
      causes of dehiscence is described. The technique consists of 3 additional
      overlapping longitudinal wires set on both sides of the sternum. Over 2 years,
      this technique was applied in 34 patients, with complete sternal re-fixation in
      all, and no signs of recurrence on follow-up.

PMID- 17005897
TI  - Primary left atrial leiomyosarcoma: literature review and lessons of a case.
AB  - Primary cardiac sarcoma is an uncommon disease. In particular, leiomyosarcoma of
      cardiovascular origin is extremely rare. Half of all cardiac leiomyosarcomas are
      located in the left atrium. Due to the extreme rarity of left atrial
      leiomyosarcoma, there is no great experience in its management. This review
      includes a report of a case of left atrial leiomyosarcoma followed up over 45
      months. The literature review examines the distribution of left atrial
      leiomyosarcoma, the physiological reasons for the tendency of cardiac
      leiomyosarcoma to be localized to the left atrial cavity, the clinical and
      physical appearance of this disease, and the key differences between left atrial
      leiomyosarcoma and the most common left atrial tumor, myxoma. The morphological
      features, using light and electron microscopy and immunochemical staining, are
      discussed. Treatment modalities including adjuvant therapy and surgical resection
      are examined and their effectiveness compared. Opinions regarding the results and
      optimal treatment of leiomyosarcoma are not always in agreement. This highlights
      the need for inter-hospital comparison to determine the optimal treatment
      regimen.

PMID- 17005898
TI  - Aortic pseudoaneurysm rupture into the oesophagus.

PMID- 17005899
TI  - Shot through the heart.

PMID- 17005900
TI  - Cardiopulmonary bypass in sickle cell disease.

PMID- 17005901
TI  - Left main coronary stenosis or left coronary artery from pulmonary artery?

PMID- 17005902
TI  - In vivo responsiveness to ezetimibe correlates with niemann-pick C1 like-1
      (NPC1L1) binding affinity: Comparison of multiple species NPC1L1 orthologs.
AB  - Ezetimibe is the first in class 2-azetidinone that decreases plasma cholesterol
      by blocking intestinal cholesterol absorption. Ezetimibe effectively reduces
      plasma cholesterol in several species including human, monkey, dog, hamster, rat,
      and mouse, but the potency ranges widely. One potential factor responsible for
      this variation in responsiveness is diversity in ezetimibe metabolism. After oral
      administration, ezetimibe is glucuronidated. Both ezetimibe and the glucuronide
      lower plasma cholesterol; however, the glucuronide exhibits greater potency.
      Recent identification of Niemann-Pick C1 Like-1 (NPC1L1) as the molecular target
      of ezetimibe enables direct binding studies to be performed. Here, we report the
      cloning of NPC1L1 derived from multiple species and assess amino acid sequence
      homology among human, monkey, dog, hamster, rat, and mouse. The rank order of
      affinity of glucuronidated ezetimibe for NPC1L1 in each species correlates with
      the rank order of in vivo activity with monkey > dog > hamster and rat >> mouse.
      Ezetimibe analogs that bind to NPC1L1 exhibit in vivo cholesterol-lowering
      activity, whereas compounds that do not bind NPC1L1 are inactive. Specific
      structural components of ezetimibe are identified as critical for binding to
      NPC1L1. The results demonstrate that small variations in ezetimibe structure or
      in NPC1L1 amino acid sequence can profoundly influence ezetimibe/NPC1L1
      interaction and consequently in vivo activity. The results demonstrate that the
      ability of compounds to bind to NPC1L1 is the major determinant of in vivo
      responsiveness.

PMID- 17005904
TI  - Interaction of the mu-opioid receptor with synaptophysin influences receptor
      trafficking and signaling.
AB  - There is increasing evidence that the signal transduction of opioid receptors is
      modulated by receptor-associated proteins. In the search for proteins regulating
      mu-opioid receptor (MOPr) endocytosis, synaptophysin was found to bind to the rat
      micro-opioid receptor in yeast two-hybrid assay. Coimmunoprecipitation
      experiments and bioluminescence resonance energy transfer assays confirmed that
      the micro-opioid receptor constitutively interacts with synaptophysin in human
      embryonic kidney 293 cells overexpressing MOPr and synaptophysin. In this study,
      we show that overexpression of synaptophysin enhances the micro-opioid receptor
      endocytosis. One explanation for the observed effects is that synaptophysin
      recruits dynamin to the plasma membrane, facilitating fission of clathrin-coated
      vesicles. This suggestion is supported by our finding that overexpression of a
      synaptophysin truncation mutant, which breaks the interaction between
      synaptophysin and dynamin, prevents agonist-mediated micro-opioid receptor
      endocytosis. In addition, the synaptophysin-augmented micro-opioid receptor
      trafficking leads to attenuated agonist-induced receptor desensitization and
      faster receptor resensitization. Taken together, our findings strongly suggest
      that synaptophysin plays an important role in the regulation of micro-opioid
      receptor trafficking and signaling.

PMID- 17005903
TI  - Mu-opioid receptor activation modulates transient receptor potential vanilloid 1
      (TRPV1) currents in sensory neurons in a model of inflammatory pain.
AB  - Current therapy for inflammatory pain includes the peripheral application of
      opioid receptor agonists. Activation of opioid receptors modulates voltage-gated
      ion channels, but it is unclear whether opioids can also influence ligand-gated
      ion channels [e.g., the transient receptor potential vanilloid type 1 (TRPV1)].
      TRPV1 channels are involved in the development of thermal hypersensitivity
      associated with tissue inflammation. In this study, we investigated mu-opioid
      receptor and TRPV1 expression in primary afferent neurons in the dorsal root
      ganglion (DRG) in complete Freund's adjuvant (CFA)-induced paw inflammation. In
      addition, the present study examined whether the activity of TRPV1 in DRG neurons
      can be inhibited by mu-opioid receptor (mu-receptor) ligands and whether this
      inhibition is increased after CFA inflammation. Immunohistochemistry demonstrated
      colocalization of TRPV1 and mu-receptors in DRG neurons. CFA-induced inflammation
      increased significantly the number of TRPV1- and mu-receptor-positive DRG
      neurons, as well as TRPV1 binding sites. In whole-cell patch clamp studies,
      opioids significantly decreased capsaicin-induced TRPV1 currents in a naloxone-
      and pertussis toxinsensitive manner. The inhibitory effect of morphine on TRPV1
      was abolished by forskolin and 8-bromo-cAMP. During inflammation, an increase in
      TRPV1 is apparently rivaled by an increase of mu-receptors. However, in single
      dissociated DRG neurons, the inhibitory effects of morphine are not different
      between animals with and without CFA inflammation. In in vivo experiments, we
      found that locally applied morphine reduced capsaicin-induced thermal allodynia.
      In summary, our results indicate that mu-receptor activation can inhibit the
      activity of TRPV1 via G(i/o) proteins and the cAMP pathway. These observations
      demonstrate an important new mechanism underlying the analgesic efficacy of
      peripherally acting mu-receptor ligands in inflammatory pain.

PMID- 17005906
TI  - Interview with Dr. Lee-Ann Allen regarding Pivotal Advance: Francisella
      tularensis LVS evades killing by human neutrophils via inhibition of the
      respiratory burst and phagosome escape. Interview by Helene F. Rosenberg.

PMID- 17005905
TI  - Mycobacteria directly induce cytoskeletal rearrangements for macrophage spreading
      and polarization through TLR2-dependent PI3K signaling.
AB  - Macrophage migration and adhesion are important for the control of mycobacterial
      infection and are critically dependent on the reorganization of the cytoskeleton.
      Mycobacteria elicit rapid morphological changes, such as cell spreading, a
      process relevant to in vivo changes of macrophage shape during extravasation and
      migration. In this study, we investigated the BCG mycobacteria-induced signaling
      events leading to macrophage cytoskeletal rearrangements employing specific
      pharmacological inhibitors to suppress distinct kinase pathways known to be
      elicited by infection. Viable or lysed mycobacteria, as well as purified cell
      wall lipoprotein p19, TLR2 agonist, induced RAW264.7 cells to extend actin-rich
      pseudopods, which impart radial spreading within 3 h, leading later to persistent
      cell polarization. BCG induced rapid activation of phosphatidylinositol 3-kinase,
      PI3K, activation that was recruited to the activated TLR2 receptor. TLR2-
      neutralizing antibody inhibited macrophage spreading and PI3K activation induced
      by p19. Additionally, BCG induced spreading and polarization of bone marrow
      derived macrophages from TLR2- expressing mice in contrast to their TLR2-knockout
      counterparts. Neither MEK1/ERK, p38 MAPK, nor NF-kappaB activation were important
      for the early cytoskeletal rearrangements observed, although suppression of these
      pathways is known to inhibit chemokine secretion by activated macrophages. Beta2
      integrins blockade with a corresponding antibody inhibited macrophage spreading
      and polarization but had no effect on pseudopodia protrusions demonstrating the
      downstream position of integrin-mediated adhesion in PI3K- dependent signaling
      pathway leading to the motility phenotype. The obtained data demonstrate that the
      direct effect of mycobacteria on macrophage shape might be mediated through TLR2
      dependent PI3K activation.

PMID- 17005907
TI  - The influence on the immunomodulatory effects of dying and dead cells of Annexin
      V.
AB  - Apoptotic and necrotic cells expose phosphatidylserine (PS). This membrane
      modification ensures a swift recognition and uptake by phagocytes of the dying
      and dead cells. Annexin V (AxV) preferentially binds to anionic phospholipids and
      thereby, modulates the clearance process. First, we analyzed the influence of AxV
      on the immunogenicity of apoptotic cells. The addition to apoptotic cells of AxV
      prior to their injection into mice increased their immunogenicity significantly.
      Next, we studied the influence of endogenous AxV on the allogeneic reaction
      against apoptotic and necrotic cells. To preserve heat-labile, short-lived
      "danger signals," we induced necrosis by mechanical stress. Wild-type mice showed
      a strong, allogeneic delayed-type hypersensitivity (DTH) reaction. In contrast,
      AxV-deficient animals showed almost no allogeneic DTH reaction, indicating that
      endogenous AxV increases the immune response against dead cells. Furthermore, AxV
      deficient macrophages had a higher immunosuppressive potential in vitro. Next, we
      analyzed the influence of AxV on chronic macrophage infection with HIV-1, known
      to expose PS on its surface. The infectivity in human macrophages of HIV-1 was
      reduced significantly in the presence of AxV. Finally, we show that AxV also
      blocked the in vitro uptake by macrophages of primary necrotic cells. Similar to
      apoptotic cells, necrotic cells generated by heat treatment displayed an anti
      inflammatory activity. In contrast, mechanical stress-induced necrotic cells led
      to a decreased secretion of IL-10, indicating a more inflammatory potential. From
      the experiments presented above, we conclude that AxV influences the clearance of
      several PS-exposing particles such as viruses, dying, and dead cells.

PMID- 17005908
TI  - Comparative gene expression by WC1+ gammadelta and CD4+ alphabeta T lymphocytes,
      which respond to Anaplasma marginale, demonstrates higher expression of
      chemokines and other myeloid cell-associated genes by WC1+ gammadelta T cells.
AB  - The functions of gammadelta T cells are enigmatic, and these cells are often
      considered as evolutionary remnants of well-characterized alphabeta T cells.
      However, their conservation throughout evolution suggests that gammadelta T cells
      are biologically unique. In ruminants, gammadelta T cells expressing the workshop
      cluster 1 (WC1) scavenger receptor comprise a large proportion of circulating
      lymphocytes, suggesting these cells are biologically relevant and functionally
      different from alphabeta T cells. In fact, bovine WC1(+) gammadelta T cells can
      act as APC for alphabeta T cells, indicating they may express genes encoding
      proteins associated with innate immunity. The present study was designed to
      compare immune function gene expression profiles of clonal populations of WC1(+)
      gammadelta and CD4(+) alphabeta T cells derived from the same animal, which
      respond to major surface protein 2 (MSP2) of the intraerythrocytic rickettsial
      pathogen of cattle, Anaplasma marginale. Gene expression profiles of activated T
      cell clones were compared using a microarray format, and differential gene
      expression was confirmed by real-time RT-PCR and protein analyses. We demonstrate
      that although MSP2-specific alphabeta and gammadelta T cell clones express many
      of the same genes, gammadelta T cell clones express high levels of genes
      associated with myeloid cells, including chemokines CCL2, CXCL1, CXCL2, CXCL6,
      and surface receptors CD68, CD11b, macrophage scavenger receptor 1, macrophage
      mannose receptor, and galectin-3. It is important that many of these genes were
      also expressed at higher levels in polyclonal WC1(+) gammadelta T cells when
      compared with CD4(+) alphabeta T cells selected from peripheral blood.

PMID- 17005910
TI  - Rendezvin: An essential gene encoding independent, differentially secreted egg
      proteins that organize the fertilization envelope proteome after self
      association.
AB  - Preventing polyspermy during animal fertilization relies on modifications to the
      egg's extracellular matrix. On fertilization in sea urchins, the contents of
      cortical granules are secreted and rapidly assemble into the egg's extracellular
      vitelline layer, forming the fertilization envelope, a proteinaceous structure
      that protects the zygote from subsequent sperm. Here, we document rendezvin, a
      gene whose transcript is differentially spliced to yield proteins destined for
      either cortical granules or the vitelline layer. These distinctly trafficked
      variants reunite after cortical granule secretion at fertilization. Together,
      they help coordinate assembly of the functional fertilization envelope, whose
      proteome is now defined in full.

PMID- 17005909
TI  - Rho2 is a target of the farnesyltransferase Cpp1 and acts upstream of Pmk1
      mitogen-activated protein kinase signaling in fission yeast.
AB  - We have previously demonstrated that knockout of the calcineurin gene or
      inhibition of calcineurin activity by immunosuppressants resulted in
      hypersensitivity to Cl- in fission yeast. We also demonstrated that knockout of
      the components of the Pmk1 mitogen-activated protein kinase (MAPK) pathway, such
      as Pmk1 or Pek1 complemented the hypersensitivity to Cl-. Using this interaction
      between calcineurin and Pmk1 MAPK, here we developed a genetic screen that aims
      to identify new regulators of the Pmk1 signaling and isolated vic (viable in the
      presence of immunosuppressant and chloride ion) mutants. One of the mutants, vic1
      1, carried a missense mutation in the cpp1+ gene encoding a beta subunit of the
      protein farnesyltransferase, which caused an amino acid substitution of aspartate
      155 of Cpp1 to asparagine (Cpp1(D155N)). Analysis of the mutant strain revealed
      that Rho2 is a novel target of Cpp1. Moreover, Cpp1 and Rho2 act upstream of Pck2
      Pmk1 MAPK signaling pathway, thereby resulting in the vic phenotype upon their
      mutations. Interestingly, compared with other substrates of Cpp1, defects of Rho2
      function were more phenotypically manifested by the Cpp1(D155N) mutation.
      Together, our results demonstrate that Cpp1 is a key component of the Pck2-Pmk1
      signaling through the spatial control of the small GTPase Rho2.

PMID- 17005911
TI  - Not all secretory granules are created equal: Partitioning of soluble content
      proteins.
AB  - Secretory granules carrying fluorescent cargo proteins are widely used to study
      granule biogenesis, maturation, and regulated exocytosis. We fused the soluble
      secretory protein peptidylglycine alpha-hydroxylating monooxygenase (PHM) to
      green fluorescent protein (GFP) to study granule formation. When expressed in AtT
      20 or GH3 cells, the PHM-GFP fusion protein partitioned from endogenous hormone
      (adrenocorticotropic hormone, growth hormone) into separate secretory granule
      pools. Both exogenous and endogenous granule proteins were stored and released in
      response to secretagogue. Importantly, we found that segregation of content
      proteins is not an artifact of overexpression nor peculiar to GFP-tagged
      proteins. Neither luminal acidification nor cholesterol-rich membrane
      microdomains play essential roles in soluble content protein segregation. Our
      data suggest that intrinsic biophysical properties of cargo proteins govern their
      differential sorting, with segregation occurring during the process of granule
      maturation. Proteins that can self-aggregate are likely to partition into
      separate granules, which can accommodate only a few thousand copies of any
      content protein; proteins that lack tertiary structure are more likely to
      distribute homogeneously into secretory granules. Therefore, a simple "self
      aggregation default" theory may explain the little acknowledged, but commonly
      observed, tendency for both naturally occurring and exogenous content proteins to
      segregate from each other into distinct secretory granules.

PMID- 17005912
TI  - TIF1 activates the intra-S-phase checkpoint response in the diploid micronucleus
      and amitotic polyploid macronucleus of Tetrahymena.
AB  - The ribosomal DNA origin binding protein Tif1p regulates the timing of rDNA
      replication and is required globally for proper S-phase progression and division
      of the Tetrahymena thermophila macronucleus. Here, we show that Tif1p safeguards
      chromosomes from DNA damage in the mitotic micronucleus and amitotic
      macronucleus. TIF1p localization is dynamically regulated as it moves into the
      micro- and macronucleus during the respective S phases. TIF1 disruption mutants
      are hypersensitive to hydroxyurea and methylmethanesulfonate, inducers of DNA
      damage and intra-S-phase checkpoint arrest in all examined eukaryotes. TIF1
      mutants incur double-strand breaks in the absence of exogenous genotoxic stress,
      destabilizing all five micronuclear chromosomes. Wild-type Tetrahymena elicits an
      intra-S-phase checkpoint response that is induced by hydroxyurea and suppressed
      by caffeine, an inhibitor of the apical checkpoint kinase ATR/MEC1. In contrast,
      hydroxyurea-challenged TIF1 mutants fail to arrest in S phase or exhibit caffeine
      sensitive Rad51 overexpression, indicating the involvement of TIF1 in checkpoint
      activation. Although aberrant micro- and macronuclear division occurs in TIF1
      mutants and caffeine-treated wild-type cells, TIF1p bears no similarity to ATR or
      its substrates. We propose that TIF1 and ATR function in the same epistatic
      pathway to regulate checkpoint responses in the diploid mitotic micronucleus and
      polyploid amitotic macronucleus.

PMID- 17005913
TI  - DNA replication origin interference increases the spacing between initiation
      events in human cells.
AB  - Mammalian DNA replication origins localize to sites that range from base pairs to
      tens of kilobases. A regular distribution of initiations in individual cell
      cycles suggests that only a limited number of these numerous potential start
      sites are converted into activated origins. Origin interference can silence
      redundant origins; however, it is currently unknown whether interference
      participates in spacing functional human initiation events. By using a novel
      hybridization strategy, genomic Morse code, on single combed DNA molecules from
      primary keratinocytes, we report the initiation sites present on 1.5 Mb of human
      chromosome 14q11.2. We confirm that initiation zones are widespread in human
      cells, map to intergenic regions, and contain sequence motifs found at other
      mammalian initiation zones. Origins used per cell cycle are less abundant than
      the potential sites of initiation, and their limited use increases the spacing
      between initiation events. Between-zone interference decreases in proportion to
      the distance from the active origin, whereas within-zone interference is 100%
      efficient. These results identify a hierarchical organization of origin activity
      in human cells. Functional origins govern the probability that nearby origins
      will fire in the context of multiple potential start sites of DNA replication,
      and this is mediated by origin interference.

PMID- 17005915
TI  - D2-like dopamine receptors depolarize dorsal raphe serotonin neurons through the
      activation of nonselective cationic conductance.
AB  - The dorsal raphe (DR) receives a prominent dopamine (DA) input that has been
      suggested to play a key role in the regulation of central serotoninergic
      transmission. DA is known to directly depolarize DR serotonin neurons, but the
      underlying mechanisms are not well understood. Here, we show that activation of
      D2-like dopamine receptors on DR 5-HT neurons elicits a membrane depolarization
      and an inward current associated with an increase in membrane conductance. The DA
      induced inward current (I(DA)) exhibits a linear I-V relationship and reverses
      polarity at around -15 mV, suggesting the involvement of a mixed cationic
      conductance. Consistent with this notion, lowering the extracellular
      concentration of sodium reduces the amplitude of I(DA) and induces a negative
      shift of its reversal potential to approximately -45 mV. This current is
      abolished by inhibiting G-protein function with GDPbetaS. Examination of the
      downstream signaling mechanisms reveals that activation of the nonselective
      cation current requires the stimulation of phospholipase C but not an increase in
      intracellular calcium. Thus, pharmacological inhibition of phospholipase C
      reduces the amplitude of I(DA). In contrast, buffering intracellular calcium has
      no effect on the amplitude of I(DA). Bath application of transient receptor
      potential (TRP) channels blockers, 2-aminoethoxydiphenyl borate and SKF96365 [1
      (beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole], strongly
      inhibits I(DA) amplitude, suggesting the involvement of TRP-like conductance.
      These results reveal previously unsuspected mechanism by which D2-like DA
      receptors induce membrane depolarization and enhance the excitability of DR 5-HT
      neurons.

PMID- 17005914
TI  - The yeast tumor suppressor homologue Sro7p is required for targeting of the
      sodium pumping ATPase to the cell surface.
AB  - The SRO7/SOP1 encoded tumor suppressor homologue of Saccharomyces cerevisiae is
      required for maintenance of ion homeostasis in cells exposed to NaCl stress. Here
      we show that the NaCl sensitivity of the sro7Delta mutant is due to defective
      sorting of Ena1p, the main sodium pump in yeast. On exposure of sro7Delta mutants
      to NaCl stress, Ena1p fails to be targeted to the cell surface, but is instead
      routed to the vacuole for degradation via the multivesicular endosome pathway.
      SRO7-deficient mutants accumulate post-Golgi vesicles at high salinity, in
      agreement with a previously described role for Sro7p in late exocytosis. However,
      Ena1p is not sorted into these post-Golgi vesicles, in contrast to what is
      observed for the vesicles that accumulate when exocytosis is blocked in sec6-4
      mutants at high salinity. These observations imply that Sro7p has a previously
      unrecognized role for sorting of specific proteins into the exocytic pathway.
      Screening for multicopy suppressors identified RSN1, encoding a transmembrane
      protein of unknown function. Overexpression of RSN1 restores NaCl tolerance of
      sro7Delta mutants by retargeting Ena1p to the plasma membrane. We propose a model
      in which blocked exocytic sorting in sro7Delta mutants, gives rise to quality
      control-mediated routing of Ena1p to the vacuole.

PMID- 17005916
TI  - BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a
      nonimidazole inverse agonist/antagonist at the human histamine H3 receptor:
      Preclinical pharmacology.
AB  - Histamine H3 receptor inverse agonists are known to enhance the activity of
      histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3
      [3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel,
      potent, and selective nonimidazole inverse agonist at the recombinant human H3
      receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding
      to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of
      0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic
      activity approximately 50% higher than that of ciproxifan. Its in vitro potency
      was approximately 6 times lower at the rodent receptor. In mice, the oral
      bioavailability coefficient, i.e., the ratio of plasma areas under the curve
      after oral and i.v. administrations, respectively, was 84%. BF2.649 dose
      dependently enhanced tele-methylhistamine levels in mouse brain, an index of
      histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response
      that persisted after repeated administrations for 17 days. In rats, the drug
      enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal
      cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states
      and also enhanced fast cortical rhythms of the electroencephalogram, known to be
      associated with improved vigilance. On the two-trial object recognition test in
      mice, a promnesiant effect was shown regarding either scopolamine-induced or
      natural forgetting. These preclinical data suggest that BF2.649 is a valuable
      drug candidate to be developed in wakefulness or memory deficits and other
      cognitive disorders.

PMID- 17005917
TI  - Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance
      protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport.
AB  - Methotrexate (MTX) has been used in combination with nonsteroidal anti
      inflammatory drugs (NSAIDs) in the treatment of inflammatory diseases as well as
      malignancies. Especially at high MTX dosages, severe adverse effects with this
      combination may occur, usually resulting from an impaired renal elimination. It
      has been shown that the mechanism of this interaction cannot be fully attributed
      to inhibition of basolateral MTX uptake in renal proximal tubules. Here, we
      studied the effect of various NSAIDs on MTX transport in membrane vesicles
      isolated from cells overexpressing the proximal tubular apical efflux
      transporters human multidrug resistance protein (MRP) 2/ABCC2 and MRP4/ABCC4. MTX
      was transported by MRP2 and MRP4 with Km values of 480 +/- 90 and 220 +/- 70
      microM, respectively. The inhibitory potency of the NSAIDs was generally higher
      against MRP4- than MRP2-mediated MTX transport, with therapeutically relevant
      IC50 values, ranging from approximately 2 microM to 1.8 mM. Salicylate,
      piroxicam, ibuprofen, naproxen, sulindac, tolmetin, and etodolac inhibited MRP2-
      and MRP4-mediated MTX transport according to a one-site competition model. In
      some cases, more complex interaction patterns were observed. Inhibition of MRP4
      by diclofenac and MRP2 by indomethacin and ketoprofen followed a two-site
      competition model. Phenylbutazone stimulated MRP2 and celecoxib MRP4 transport at
      low concentrations and inhibited both transporters at high concentration. Our
      data suggest that the inhibition by NSAIDs of renal MTX efflux via MRP2 and MRP4
      is a potential new site and mechanism contributing to the overall interaction
      between these drugs.

PMID- 17005918
TI  - The nitric oxide-donating pravastatin derivative, NCX 6550 [(1S-[1alpha(betaS*,
      deltaS*), 2alpha, 6alpha, 8beta-(R*), 8a alpha]]-1,2,6,7,8,8a-Hexahydro-beta,
      delta, 6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphtalene-heptanoic acid
      4-(nitrooxy)butyl ester)], reduces splenocyte adhesion and reactive oxygen
      species generation in normal and atherosclerotic mice.
AB  - Statins possess anti-inflammatory effects that may contribute to their ability to
      slow atherogenesis, whereas nitric oxide (NO) also influences inflammatory cell
      adhesion. This study aimed to determine whether a novel NO-donating pravastatin
      derivative, NCX 6550 [(1S-[1alpha(betaS*,deltaS*),2alpha,6alpha,8beta-(R*),8a
      alpha]]-1,2,6,7,8,8a-hexahydro-beta,delta,6-trihydroxy-2-methyl-8-(2-methyl-1
      oxobutoxy)-1-naphthalene-heptanoic acid 4-(nitrooxy)butyl ester)], has greater
      anti-inflammatory properties compared with pravastatin in normal and
      atherosclerotic apolipoprotein E receptor knockout (ApoE-/-) mice. C57BL/6 and
      ApoE-/- mice were administered pravastatin (40 mg/kg), NCX 6550 (48.5 mg/kg), or
      vehicle orally for 5 days. Ex vivo studies assessed splenocyte adhesion to
      arterial segments and splenocyte reactive oxygen species (ROS) generation. NCX
      6550 significantly reduced splenocyte adhesion to artery segments in both C57BL/6
      (8.8 +/- 1.9% versus 16.6 +/- 6.7% adhesion; P < 0.05) and ApoE-/- mice (9.3 +/-
      2.9% versus 23.4 +/- 4.6% adhesion; P < 0.05) concomitant with an inhibition of
      endothelial intercellular adhesion molecule-1 expression. NCX 6550 also
      significantly reduced phorbol 12-myristate 13-acetate-induced ROS production that
      was enhanced in isolated ApoE-/- splenocytes. Conversely, pravastatin had no
      significant effects on adhesion in normal or ApoE-/- mice but reduced the
      enhanced ROS production from ApoE-/- splenocytes. In separate groups of ApoE-/-
      mice, NCX 6550 significantly enhanced endothelium-dependent relaxation to
      carbachol in aortic segments precon-tracted with phenylephrine (-logEC(50), 6.37
      +/- 0.37) compared with both vehicle-treated (-logEC50, 5.81 +/- 0.15; P < 0.001)
      and pravastatin-treated (-logEC50, 5.57 +/- 0.45; P < 0.05) mice. NCX 6550 also
      significantly reduced plasma monocyte chemoattractant protein-1 levels (648.8
      pg/ml) compared with both vehicle (1191.1 pg/ml; P < 0.001) and pravastatin (847
      +/- 71.0 pg/ml; P < 0.05) treatment. These data show that NCX 6550 exerts
      superior anti-inflammatory actions compared with pravastatin, possibly through NO
      related mechanisms.

PMID- 17005919
TI  - Use-dependent block by lidocaine but not amitriptyline is more pronounced in
      tetrodotoxin (TTX)-Resistant Nav1.8 than in TTX-sensitive Na+ channels.
AB  - The excitability of sensory neurons depends on the expression of various voltage
      gated Na+ channel isoforms. The tetrodotoxin-resistant (TTXr) Na+ channel
      Na(v)1.8 accounts for the electroresponsiveness of nociceptive neurons and
      contributes to inflammatory and neuropathic pain. Na+ channel blockers are
      clinically employed for chronic pain management, but side effects limit their
      use. There is conflicting information whether their potency to block tetrodotoxin
      sensitive (TTXs) and TTXr Na+ channels differs. We analyzed the action of
      lidocaine and amitriptyline on TTXr Na(v)1.8 heterologously expressed in ND7/23
      cells in comparison with TTXs Na+ channels endogenously expressed in ND7/23
      cells. TTXr Na(v)1.8 and TTXs currents were investigated under whole-cell voltage
      clamp. At a holding potential of -80 mV, lidocaine was 5-fold and amitriptyline 8
      fold more potent to tonically block TTXs than Na(v)1.8 currents. This was due to
      a higher percentage of TTXs channels residing in the inactivated, high-affinity
      state at this potential. Tonic block of either resting or inactivated channels by
      lidocaine or amitriptyline revealed little differences between TTXs and Na(v)1.8
      channels. Use-dependent block by amitriptyline was similar in TTXs and Na(v)1.8
      channels. Surprisingly, use-dependent block by lidocaine was more pronounced in
      Na(v)1.8 than in TTXs channels. This result was confirmed in dorsal root ganglion
      neurons and is associated with the greater tendency of Na(v)1.8 to enter a slow
      inactivated state. Our data suggest that lidocaine could selectively block
      Na(v)1.8-mediated action potential firing. It is conceivable that the expression
      pattern of Na+ channels in sensory neurons might influence the efficiency of Na+
      channel blockers used for chronic pain management.

PMID- 17005920
TI  - Duplicate maize 13-lipoxygenase genes are differentially regulated by circadian
      rhythm, cold stress, wounding, pathogen infection, and hormonal treatments.
AB  - Most plant oxylipins, a large class of diverse oxygenated polyunsaturated fatty
      acids and their derivatives, are produced through the lipoxygenase (LOX) pathway.
      Recent progress in dicots has highlighted the biological roles of oxylipins in
      plant defence responses to pathogens and pests. By contrast, the physiological
      function of LOXs and their metabolites in monocots is poorly understood. Two
      maize LOXs, ZmLOX10 and ZmLOX11 that share >90% amino acid sequence identity but
      are localized on different chromosomes, were cloned and characterized.
      Phylogenetic analysis revealed that ZmLOX10 and ZmLOX11 cluster together with
      well-characterized plastidic type 2 linoleate 13-LOXs from diverse plant species.
      Regio-specificity analysis of recombinant ZmLOX10 protein overexpressed in
      Escherichia coli proved it to be a linoleate 13-LOX with a pH optimum at
      approximately pH 8.0. Both predicted proteins contain putative transit peptides
      for chloroplast import. ZmLOX10 was preferentially expressed in leaves and was
      induced in response to wounding, cold stress, defence-related hormones jasmonic
      acid (JA), salicylic acid (SA), and abscisic acid (ABA), and inoculation with an
      avirulent strain of Cochliobolus carbonum. These data suggested a role for this
      gene in maize adaptation to abiotic stresses and defence responses against
      pathogens and pests. ZmLOX11 was preferentially expressed in silks and was
      induced in leaves only by ABA, indicating its possible involvement in responses
      to osmotic stress. In leaves, mRNA accumulation of ZmLOX10 is strictly regulated
      by a circadian rhythm, with maximal expression coinciding temporally with the
      highest photosynthetic activity. This study reveals the evolutionary divergence
      of physiological roles for relatively recently duplicated genes. Possible
      physiological functions of these 13-LOXs are suggested.

PMID- 17005921
TI  - Flower-like terminal structures in racemose inflorescences: a tool in
      morphogenetic and evolutionary research.
AB  - Terminal flower-like structures (TFLS) occur in many angiosperms that possess
      indeterminate inflorescences such as spikes, racemes, or spadices. We describe
      and review TFLS in early-divergent angiosperms, especially the magnoliid order
      Piperales and the monocot order Alismatales, in which floral interpretation is
      controversial. Essentially similar TFLS occur in a wide range of taxa. Among
      magnoliids, they occur in some Piperales (Saururaceae and a few Piperaceae), but
      are absent from Chloranthaceae. Among monocots, they occur in some early
      divergent families such as Acoraceae, Aponogetonaceae, Juncaginaceae,
      Potamogetonaceae, and Ruppiaceae. Similar TFLS with obscure organ identity are
      recorded in mutants of Arabidopsis. TFLS can often be interpreted as pseudanthia
      (close aggregations of reduced flowers), but in some cases the entire terminal
      pseudanthium is very similar to a true flower. In some cases, elaborated TFLS
      could therefore have given rise to what are normally termed 'true' (i.e.
      euanthial) flowers. Data presented here on terminal pseudanthia in Potamogeton
      and Ruppia support a pseudanthial evolutionary origin of reproductive units in
      the alismatid families Zannichelliaceae and Cymodoceaceae. Furthermore, in some
      alismatid species, either the entire inflorescence apex or an individual
      primordium at or near the inflorescence tip can be transformed into a filamentous
      or tubular (or intermediate) structure. A tubular structure enclosing stamens and
      carpels is described in Piper. This indicates that pseudanthium formation can
      provoke morphological novelties, perhaps due to new patterns of overlap between
      expression zones of regulatory genes and/or new spatial constraints.

PMID- 17005922
TI  - The control of flowering in time and space.
AB  - The transition to flowering is one of the most important developmental decisions
      made by plants. Classical studies have highlighted the importance of photoperiod
      in controlling flowering time. More recently, the identification of mutants
      specifically affected in the photoperiod pathway in the model system Arabidopsis
      thaliana has enabled the flowering time pathways to be placed in a molecular
      context. This review highlights recent advances in understanding how photoperiod
      signals (perceived in the leaves) act at the apex of the plant where the floral
      stimulus is perceived. The photoperiod pathway acts predominantly through the
      gene CONSTANS to activate the small signalling molecule FT. While FT
      transcription is induced in the leaves, it is essential that FT protein is
      present at the apex of the plant. FT at the apex interacts with the transcription
      factor FD to induce flowering.

PMID- 17005923
TI  - Protein interactions of MADS box transcription factors involved in flowering in
      Lolium perenne.
AB  - Regulation of flowering time is best understood in the dicot model species
      Arabidopsis thaliana. Molecular analyses revealed that genes belonging to the
      MADS box transcription factor family play pivotal regulatory roles in both the
      vernalization- and photoperiod-regulated flowering pathways. Here the analysis of
      three APETALA1 (AP1)-like MADS box proteins (LpMADS1-3) and a SHORT VEGETATIVE
      PHASE (SVP)-like MADS box protein (LpMADS10) from the monocot perennial grass
      species Lolium perenne is reported. Features of these MADS box proteins were
      studied by yeast two-hybrid assays. Protein-protein interactions among the Lolium
      proteins and with members of the Arabidopsis MADS box family have been studied.
      The expression pattern for LpMADS1 and the protein properties suggest that not
      the Arabidopsis AP1 gene, but the SUPPRESSOR OF CONSTANS1 (SOC1) gene, is the
      functional equivalent of LpMADS1. To obtain insight into the molecular mechanism
      underlying the regulation of LpMADS1 gene expression in vernalization-sensitive
      and -insensitive Lolium accessions, the upstream sequences of this gene from a
      winter and spring growth habit variety were compared with respect to MADS box
      protein binding. In both promoter elements, a putative MADS box transcription
      factor-binding site (CArG-box) is present; however, the putative spring promoter
      has a short deletion adjacent to this DNA motif. Experiments using yeast one
      hybrid and gel retardation assays demonstrated that the promoter element is bound
      by an LpMADS1-LpMADS10 higher order protein complex and, furthermore, that this
      complex binds efficiently to the promoter element from the winter variety only.
      This strongly supports the model that LpMADS1 together with LpMADS10 controls the
      vernalization-dependent regulation of the LpMADS1 gene, which is part of the
      vernalization-induced flowering process in Lolium.

PMID- 17005924
TI  - Imaging Matrix Assisted Laser Desorption Ionization Mass Spectrometry: a
      technique to map plant metabolites within tissues at high spatial resolution.
AB  - Imaging Matrix Assisted Laser Desorption Ionization Mass Spectrometry provides a
      new and powerful tool to analyse the distribution of metabolites within plant
      tissues. The two matrices alpha-cyano-4-hydroxycinnamic acid (alpha-CHCA) and 9
      aminoacridine provide a useful combination that allows the measurement of amino
      acids, sugars, and phosphorylated metabolites. Results are presented showing that
      representatives of these metabolites are unevenly distributed in wheat seeds at
      different stages of development and under temperature stress.

PMID- 17005925
TI  - Universal florigenic signals triggered by FT homologues regulate growth and
      flowering cycles in perennial day-neutral tomato.
AB  - The transition from vegetative to floral meristems in higher plants is programmed
      by the coincidence of internal and environmental signals. Classic grafting
      experiments have shown that leaves, in response to changing photoperiods, emit
      systemic signals, dubbed 'florigen', which induce flowering at the shoot apex.
      The florigen paradigm was conceived in photoperiod-sensitive plants: nevertheless
      it implies that although activated by different stimuli in different flowering
      systems, the signal is common to all plants. Tomato is a day-neutral, perennial
      plant, with sympodial and modular organization of its shoots and thus with
      reiterative regular vegetative/reproductive transitions. SINGLE FLOWER TRUSS a
      regulator of flowering-time and shoot architecture encodes the tomato orthologue
      of FT, a major flowering integrator gene in Arabidopsis. SFT generates graft
      transmissible signals which complement the morphogenetic defects in sft plants,
      substitute for light dose stimulus in tomato and for contrasting day-length
      requirements in Arabidopsis and MARYLAND MAMMOTH tobacco. It is discussed how
      systemic signals initiated by SFT interact with the SELF PRUNING gene to regulate
      vegetative to reproductive (V/R) transitions in the context of two flowering
      systems, one for primary apices and the other for sympodial shoots.

PMID- 17005926
TI  - Fast cloning inverted repeats for RNA interference.
AB  - Double-stranded RNA (dsRNA) can induce post-transcriptional gene silencing in a
      wide variety of organisms. Commonly, inverted repeats are used to produce dsRNA
      to silence genes of interest. However, cloning inverted repeats still remains a
      rate-limiting step for widely applying this technique. Here we describe a pGEM-T
      based vector, pGEM-WIZ, designed to produce inverted repeats for any Drosophila
      gene. pGEM-WIZ has a high efficiency in assembling inverted repeats and the
      repeats in this vector are stable in regular Escherichia coli strains.
      Furthermore, we have developed a method for rapid selection of clones with an
      inverted repeat based on size and relative copy number of the vector with or
      without an insert. This method further eases the cloning process. The inverted
      repeat cassette assembled in pGEM-WIZ can be easily transferred to commonly
      available expression vectors suitable for stably expressing inverted repeats in
      vitro and in vivo.

PMID- 17005927
TI  - Thermostable RNase P RNAs lacking P18 identified in the Aquificales.
AB  - The RNase P RNA (rnpB) and protein (rnpA) genes were identified in the two
      Aquificales Sulfurihydrogenibium azorense and Persephonella marina. In contrast,
      neither of the two genes has been found in the sequenced genome of their close
      relative, Aquifex aeolicus. As in most bacteria, the rnpA genes of S. azorense
      and P. marina are preceded by the rpmH gene coding for ribosomal protein L34.
      This genetic region, including several genes up- and downstream of rpmH, is
      uniquely conserved among all three Aquificales strains, except that rnpA is
      missing in A. aeolicus. The RNase P RNAs (P RNAs) of S. azorense and P. marina
      are active catalysts that can be activated by heterologous bacterial P proteins
      at low salt. Although the two P RNAs lack helix P18 and thus one of the three
      major interdomain tertiary contacts, they are more thermostable than Escherichia
      coli P RNA and require higher temperatures for proper folding. Related to their
      thermostability, both RNAs include a subset of structural idiosyncrasies in their
      S domains, which were recently demonstrated to determine the folding properties
      of the thermostable S domain of Thermus thermophilus P RNA. Unlike 16S rRNA
      phylogeny that has placed the Aquificales as the deepest lineage of the bacterial
      phylogenetic tree, RNase P RNA-based phylogeny groups S. azorense and P. marina
      with the green sulfur, cyanobacterial, and delta/epsilon proteobacterial
      branches.

PMID- 17005928
TI  - Quantitative and functional differences between peripheral blood myeloid
      dendritic cells from patients with pleural and parenchymal lung tuberculosis.
AB  - Dendritic cells (DCs) play a pivotal role in generating protective host immunity
      to Mycobacterium tuberculosis. Few studies have addressed DC function in the
      context of active tuberculosis (TB), largely due to technical constraints in
      obtaining adequate numbers of DC from sick patients. We quantitated peripheral
      blood myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in the whole blood of
      patients with active TB and show that blood from patients with pleural TB was
      characterized by high circulating levels of mDCs. We also developed and optimized
      a novel whole-blood assay to study mDC production of the Th1-promoting cytokine
      interleukin 12 (IL-12) and upregulation of the maturation marker CCR7 after
      incubation with mycobacteria. We found that pleural TB was associated with
      increased IL-12 production and CCR7 expression compared to lung parenchymal
      disease. Our findings suggest important differences in innate immunity between
      patients with different forms of active TB, and this may contribute to the
      differences in natural history observed between the two groups.

PMID- 17005929
TI  - Flow cytometric detection of gamma interferon can effectively discriminate
      Mycobacterium bovis BCG-vaccinated cattle from M. bovis-infected cattle.
AB  - Mycobacterium bovis is the causative agent of bovine tuberculosis, a disease that
      is increasing in incidence in United Kingdom cattle herds. In addition to
      increasing economic losses, the rise in bovine tuberculosis poses a human health
      risk. There is an urgent requirement for effective strategies for disease
      eradication; this will likely involve vaccination in conjunction with current
      test and slaughter policies. A policy involving vaccination would require an
      accurate diagnosis of M. bovis-infected animals and the potential to distinguish
      these animals from vaccinates. Currently used diagnostic tests, the skin test and
      gamma interferon (IFN-gamma) blood test, have a sensitivity of up to 95%. A
      further complication is that M. bovis BCG-vaccinated animals are also scored
      positive by these tests. We tested the hypothesis that the quantification of IFN
      gamma-producing lymphocytes by flow cytometric analysis of intracellular IFN
      gamma expression would provide a more accurate discrimination of M. bovis
      infected animals from BCG vaccinates. Significant numbers of IFN-gamma-expressing
      CD4+ T cells were detected following culture of heparinized blood from M. bovis
      infected animals, but not from BCG vaccinates, with purified protein derived from
      M. bovis (PPD-B) or live mycobacteria. Only 1 of 17 BCG-vaccinated animals had a
      significant number of CD4+ T lymphocytes expressing IFN-gamma, compared with
      21/22 M. bovis-infected animals. This assay could allow an accurate diagnosis of
      M. bovis and allow the discrimination of BCG-vaccinated cattle from infected
      cattle.

PMID- 17005930
TI  - A nephritogenic peptide induces intermolecular epitope spreading on collagen IV
      in experimental autoimmune glomerulonephritis.
AB  - This group previously identified a peptide p13 of alpha3(IV)NC1 domain of type IV
      collagen that induces experimental autoimmune glomerulonephritis (EAG) in rats
      with generation of antibodies to sites on alpha3(IV)NC1 external to the peptide
      as a result of intramolecular epitope spreading. It was hypothesized that
      intermolecular epitope spreading to other collagen IV chains also was induced.
      Rats were immunized with nephritogenic peptide that was derived from the amino
      terminal part of rat alpha3(IV)NC1 domain, and serum and kidney eluate were
      examined for antibodies to both native and recombinant NC1 domains of collagen
      IV. Peptide induced EAG with proteinuria and decreased renal function and
      glomerular basement membrane IgG deposits. Sera from these rats were examined by
      ELISA, which revealed reactivity not only to immunizing peptide but also to human
      and rat alpha3(IV)NC1 and to human alpha4(IV)NC1 domains. Kidney eluate that was
      depleted of alpha3(IV)NC1 antibodies still reacted to alpha4(IV)NC1, and
      alpha3(IV)NC1 column-bound antibody reacted with alpha3(IV)NC1. There was minimal
      reactivity to other collagen chains. Eluate that was adsorbed to NC1 hexamer from
      rat glomerular basement membrane lost all reactivity to glomerular constituents,
      and the eluted antibodies reacted to alpha3(IV)NC1 and alpha4(IV)NC1 domains.
      These studies show that a T cell epitope of alpha3(IV)NC1 induces EAG,
      intramolecular epitope spreading along alpha3(IV)NC1, and intermolecular epitope
      spreading to alpha4(IV)NC1 domain with minimal or no reactivity to other collagen
      chains or glomerular constituents. This is the first demonstration in EAG of
      intermolecular epitope spreading and identification of the spread epitopes.

PMID- 17005931
TI  - Critical role of the epithelial Ca2+ channel TRPV5 in active Ca2+ reabsorption as
      revealed by TRPV5/calbindin-D28K knockout mice.
AB  - The epithelial Ca(2+) channel TRPV5 facilitates apical Ca(2+) entry during active
      Ca(2+) reabsorption in the distal convoluted tubule. In this process, cytosolic
      Ca(2+) remains at low nontoxic concentrations because the Ca(2+) influx is
      buffered rapidly by calbindin-D(28K). Subsequently, Ca(2+) that is bound to
      calbindin-D(28K) is shuttled toward the basolateral Ca(2+) extrusion systems. For
      addressing the in vivo role of TRPV5 and calbindin-D(28K) in the maintenance of
      the Ca(2+) balance, single- and double-knockout mice of TRPV5 and calbindin
      D(28K) (TRPV5(-/-), calbindin-D(28K)(-/-), and TRPV5(-/-)/calbindin-D(28K)(-/-))
      were characterized. These mice strains were fed two Ca(2+) diets (0.02 and 2%
      wt/wt) to investigate the influence of dietary Ca(2+) content on the Ca(2+)
      balance. Urine analysis indicated that TRPV5(-/-)/calbindin-D(28K)(-/-) mice
      exhibit on both diets hypercalciuria compared with wild-type mice. Ca(2+)
      excretion in TRPV5(-/-)/calbindin-D(28K)(-/-) mice was not significantly
      different from TRPV5(-/-) mice, whereas calbindin-D(28K)(-/-) mice did not show
      hypercalciuria. The similarity between TRPV5(-/-)/calbindin-D(28K)(-/-) and
      TRPV5(-/-) mice was supported further by an equivalent increase in renal
      calbindin-D(9K) expression and in intestinal Ca(2+) hyperabsorption as a result
      of upregulation of calbindin-D(9K) and TRPV6 expression in the duodenum. Elevated
      serum parathyroid hormone and 1,25-dihydroxyvitamin D(3) levels accompanied the
      enhanced expression of the Ca(2+) transporters. Intestinal Ca(2+) absorption and
      expression of calbindin-D(9K) and TRPV6, as well as serum parameters of the
      calbindin-D(28K)(-/-) mice, did not differ from those of wild-type mice. These
      results underline the gatekeeper function of TRPV5 being the rate-limiting step
      in active Ca(2+) reabsorption, unlike calbindin-D(28K), which possibly is
      compensated by calbindin-D(9K).

PMID- 17005932
TI  - Major histocompatibility complex HLA region largely explains the genetic variance
      exercised on neutrophil membrane proteinase 3 expression.
AB  - ANCA-associated vasculitides, a common cause of rapidly progressive
      glomerulonephritis, are influenced by genetic variance. Neutrophil membrane
      expression of the ANCA antigen proteinase 3 (PR3) is pathogenically important. A
      subset of membrane PR3-positive neutrophils can be distinguished from a membrane
      negative subset in any given subject. The percentage of membrane PR3-positive
      neutrophils is genetically determined. In this study, 17 pairs of HLA-matched
      siblings were typed for their percentage of membrane PR3-positive neutrophils.
      The HLA-matched siblings showed a high concordance (r = 0.67, P < 0.05), similar
      to that seen in monozygotic twins. For testing of whether the HLA system
      influences membrane PR3 percentage, membrane PR3 typing and HLA typing of 51
      unrelated patients with Wegener's granulomatosis and 49 normal control subjects
      was performed. Using two independent statistical methods, a group of 34 HLA
      antigens was found to predict a large fraction of the membrane PR3 phenotype in
      patients and control subjects. Certain major histocompatibility HLA antigens have
      been implicated to conflicting degrees in ANCA-associated vasculitides. However,
      in earlier studies, the contribution of the HLA system to the genetic variance of
      the disease was unclear. In this cohort, found was an association of Wegener's
      granulomatosis with the same group of HLA antigens that predicted for membrane
      PR3 percentage and a similar correlation with clinical parameters at initial
      presentation. The disease status in 80% of the patients and 82% of the control
      subjects could be predicted correctly on the basis of HLA typing by discriminate
      function analysis (P < 0.001). After removal of the predicted individual from the
      sample, this association remained significant (64 and 63% correct prediction; P <
      0.001). The data suggest that a complex interaction of the entire HLA system is
      responsible for the genetic influence on membrane PR3 percentage and Wegener's
      granulomatosis.

PMID- 17005933
TI  - Repetitive fragmentation products of albumin and alpha1-antitrypsin in glomerular
      diseases associated with nephrotic syndrome.
AB  - Even if nephrotic syndrome is characterized by massive urinary loss of major
      plasma proteins, a clear structural characterization based on proteomics has
      never been reported. Urine and plasma of 23 patients with different idiopathic
      nephrotic syndromes (10 steroid-sensitive minimal-change nephropathy, seven
      steroid-resistant FSGS, and six membranous glomerulonephritis) were analyzed with
      two-dimensional electrophoresis in soft gel, Western blot, and matrix-assisted
      laser desorption/ionization time of flight mass spectrometry; 72 urinary
      components corresponded to fragments of albumin and/or of alpha1-antitrypsin.
      Several repetitive fragmentation motives and a few differences among different
      pathologies were found. Several (21 of 72) urinary albumin fragments also were
      detected in plasma, although in lower concentration, suggesting a preferential
      excretion. The bulk of components with low molecular weight were detected only in
      urine, suggesting an in situ formation; zymograms with albumin as substrate
      showed the presence in urine of specific proteases. A final but not secondary
      point was the characterization of albumin adducts that harbor both the COOH and
      NH2 terminal parts of the protein, suggesting the formation of new covalent
      chemical groups. Altogether, these new findings reveal unexpected structural and
      functional aspects of proteinuria that may play a key role in pathogenesis.
      Characterization of urinary fragmentation patterns should be extended to other
      renal diseases.

PMID- 17005934
TI  - Stable knockdown of polycystin-1 confers integrin-alpha2beta1-mediated anoikis
      resistance.
AB  - The mechanisms of action of polycystin-1 (PC1) have been difficult to dissect
      because of its interaction with multiple factors, the heterogeneity of the
      genetic mutations, and the complexity of the experimental animal models. Here,
      stable knockdown of PC1 in MDCK epithelial cells was achieved by lentiviral
      mediated delivery of a specific small interfering RNA for PKD1. The reduction of
      PC1 expression prevented tubulogenesis in three-dimensional collagen type I
      culture in response to hepatocyte growth factor and induced formation of cysts.
      PC1 knockdown created a condition of haploinsufficiency that led to
      hyperproliferation, increased adhesion to collagen type I, and increased
      apoptosis. It was shown that the suppression of PC1 was associated with the
      increased expression of integrin-alpha2beta1 and reduced apoptosis in cells grown
      on collagen type I. The engagement of integrin-alpha2beta1 seemed to be essential
      for the survival because PC1 knockdown cells were significantly less susceptible
      to anoikis by a mechanism that was reversible by anti-integrin-alpha2beta1
      blocking antibodies. Overall, these data link integrin-alpha2beta1 to some of the
      biologic functions that are ascribed to PC1 and establish the potential of this
      approach for the direct study of PC1 functions in a genetically defined
      background. Furthermore, these findings indicate that reduction of PC1 expression
      levels, rather than the loss of heterozygosity, may be sufficient to induce
      cystogenesis.

PMID- 17005935
TI  - Renal damage after myocardial infarction is prevented by renin-angiotensin
      aldosterone-system intervention.
AB  - Recently, it was shown that myocardial infarction aggravates preexistent mild
      renal damage that is elicited by unilateral nephrectomy in rats. The mechanism
      behind this cardiorenal interaction likely involves the renin-angiotensin
      aldosterone-system and/or vasoactive peptides that are metabolized by neutral
      endopeptidase (NEP). The renoprotective effect of angiotensin-converting enzyme
      inhibition (ACEi) as well as combined ACE/NEP inhibition with a vasopeptidase
      inhibitor (VPI) was investigated in the same model to clarify the underlying
      mechanism. At week 17 after sequential induction of unilateral nephrectomy and
      myocardial infarction, treatment with lisinopril (ACEi), AVE7688 (VPI), or
      vehicle was initiated for 6 wk. Proteinuria and systolic BP (SBP) were evaluated
      weekly. Renal damage was assessed primarily by proteinuria, interstitial alpha
      smooth muscle actin (alpha-SMA) staining, and the incidence of focal
      glomerulosclerosis (FGS). At start of treatment, proteinuria had increased
      progressively to 167 +/- 20 mg/d in the entire cohort (n = 42). Both ACEi and VPI
      provided a similar reduction in proteinuria, alpha-SMA, and FGS compared with
      vehicle at week 23 (proteinuria 76 +/- 6 versus 77 +/- 4%; alpha-SMA 60 +/- 6
      versus 77 +/- 3%; FGS 52 +/- 14 versus 61 +/- 10%). Similar reductions in
      systolic BP were observed in both ACEi- and VPI-treated groups (33 +/- 3 and 37
      +/- 2%, respectively). Compared with ACEi, VPI-treated rats displayed a
      significantly larger reduction of plasma (41 +/- 5 versus 61 +/- 4%) and renal
      (53 +/- 6 versus 74 +/- 4%) ACE activity. It is concluded that both ACEi and VPI
      intervention prevent renal damage in a rat model of cardiorenal interaction. VPI
      treatment seemed to provide no additional renoprotection compared with sole ACEi
      after 6 wk of treatment in this model, despite a more pronounced ACE-inhibiting
      effect of VPI.

PMID- 17005936
TI  - Development of a diagnostic method for detecting increased muscle protein
      degradation in patients with catabolic conditions.
AB  - Muscle atrophy in catabolic illnesses is due largely to accelerated protein
      degradation. Unfortunately, methods for detecting accelerated muscle proteolysis
      are cumbersome. The goal of this study was to develop a method for detecting
      muscle protein breakdown and assess the effectiveness of anticatabolic therapy.
      In rodent models of catabolic conditions, it was found that accelerated muscle
      protein degradation is triggered by activation of caspase-3. Caspase-3 cleaves
      actomyosin/myofibrils to form substrates for the ubiquitin-proteasome system and
      leaves a characteristic 14-kD actin fragment in the insoluble fraction of a
      muscle lysate. Muscle biopsies were obtained from normal adults and three groups
      of patients: 14 who were undergoing hip arthroplasty, 28 hemodialysis patients
      who were participating in exercise programs, and seven severely burned patients.
      In muscle of patients who were undergoing hip arthroplasty, the 14-kD actin
      fragment level was correlated (r = 0.787, P < 0.01) with the fractional rate of
      protein degradation. In muscle of hemodialysis patients who were undergoing
      endurance exercise training, the 14-kD actin fragment decreased to values similar
      to levels in normal adults; strength training did not significantly decrease the
      actin fragment. Severely burned patients had increased muscle protein degradation
      and actin fragment levels, but the two measures were not significantly
      correlated. The experimental results suggest that the 14-kD actin fragment in
      muscle biopsies is increased in catabolic states and could be used in conjunction
      with other methods to detect and monitor changes in muscle proteolysis that occur
      in patients with mild or sustained increases in muscle proteolysis.

PMID- 17005937
TI  - Signaling mechanism of renal fibrosis in unilateral ureteral obstructive kidney
      disease in ROCK1 knockout mice.
AB  - It has been shown that blockade of Rho kinase with pharmacologic inhibitors
      inhibits renal fibrosis. This study examined the role of Rho kinase in renal
      fibrosis in the unilateral ureteral obstruction (UUO) model in mice that do not
      express the ROCK1 gene, a critical downstream mediator of Rho GTPase. Unexpected,
      real-time PCR, Western blot, and immunohistochemistry demonstrated that, compared
      with the wild-type mice, mice with ROCK1 knockout (KO) were not protected against
      renal fibrosis at both the early (day 5) and late (day 10) UUO, as determined by
      histology and expression of both mRNA and protein levels of alpha-smooth muscle
      actin, collagen types I and III, and fibronectin within the diseased kidney. Then
      the mechanisms of loss of protective effect on renal fibrosis in ROCK1 KO mice
      were investigated. It is interesting that mice that lacked ROCK1 did not have
      altered expression of ROCK2 but significantly increased TGF-beta expression and
      Smad2/3 activation (phosphorylation and nuclear translocation) in the diseased
      kidney at day 5, which remained high at day 10 of UUO. Similarly, primary
      cultures of kidney fibroblasts that were obtained from both ROCK1 wild-type and
      KO mice showed that deletion of ROCK1 did not prevent TGF-beta-induced activation
      of Smad2/3 and collagen I expression. This also was observed in the presence of
      Rho kinase inhibitor Y-27632. Taken together, results from this study suggest
      that Rho/Rho kinase may not be a necessary or a central pathway for renal
      fibrosis in the UUO model. The interplay between the Rho/Rho kinase pathway and
      the Smad signaling pathway may be a key mechanism by which loss of ROCK1 does not
      prevent renal fibrosis in the UUO model.

PMID- 17005938
TI  - Relationship between moderate to severe kidney disease and hip fracture in the
      United States.
AB  - People with ESRD are at a high risk for hip fracture. However, the effect of
      moderate to severe chronic kidney disease (CKD) on hip fracture risk has not been
      well studied. As part of the Third National Health and Nutrition Examination
      Survey, information on both kidney function and history of hip fracture was
      obtained. This survey is a complex, multistage, probability sample of the US
      noninstitutionalized civilian population and was conducted between 1988 and 1994.
      A history of hip fracture was identified from the response to a questionnaire
      that was administered to all participants. There were 159 cases of hip fracture.
      There was a significantly increased likelihood of reporting a hip fracture in
      participants with estimated GFR <60 ml/min (odds ratio [OR] 2.12; 95% confidence
      interval [CI] 1.18 to 3.80). In younger participants (aged 50 to 74 yr), the
      prevalence of CKD was approximately three-fold higher in those with a history of
      hip fracture versus in those without a history of hip fracture (19.0 versus 6.2%,
      respectively; P = 0.04). In multivariate logistic regression analysis, only the
      presence of CKD (OR 2.32; 95% CI 1.13 to 4.74), a reported history of
      osteoporosis (OR 2.52; 95% CI 1.08 to 5.91), and low physical activity levels (OR
      2.10; 95% CI 1.03 to 4.27) were associated with a history of hip fracture. There
      is a significant association between hip fracture and moderate to severe degrees
      of CKD, particularly in younger individuals, that is independent of traditional
      risk factors for hip fracture.

PMID- 17005939
TI  - Heterocomplex formation and cell-surface accumulation of hen's serum zona
      pellucida B1 (ZPB1)with ZPC expressed by a mammalian cell line (COS-7): a
      possible initiating step of egg-envelope matrix construction.
AB  - The egg envelope, referred to as zona pellucida (ZP) in mammalian eggs, is a
      fibrous and noncollagenous extracellular matrix surrounding vertebrate eggs, and
      composed of three to four homologous glycoproteins with a common ZP domain. In
      birds, a liver-derived ZP glycoprotein (ZP1/ZPB1) is transported through the
      bloodstream to ovarian follicles and joins the egg-envelope matrix construction
      together with the other ZP glycoproteins, such as ZPC and ZPD/ZPX2, both secreted
      from follicular granulosa cells. We report here that, through its ZP domain, ZPB1
      specifically associates with ZPC, which might lead to the construction of egg
      envelope matrix. The ZPB1 in laying hen's serum specifically bound to ZPC, but
      not to ZPX2, separated by SDS-PAGE and blotted on a membrane. Hemagglutinin (HA)
      tagged ZPC expressed in a mammalian cell line (COS-7) cells was processed and
      secreted as a mature-form into the culture medium. From the culture supernatant
      of ZPC-expressing transfectants cultured in the presence of ZPB1, both ZPB1 and
      ZPC were recovered as heterocomplexes by immunoprecipitation using either anti-HA
      or anti-ZPB1 antibody. Interestingly, a monoclonal antibody, 8E1, which
      immunoprecipitated free ZPB1, did not immunoprecipitate the ZPB1-ZPC
      heterocomplexes. An 8E1 epitope was mapped on a C-terminal region of the ZP
      domain in a ZPB1 molecule by identifying an 8E1-positive peptide using mass
      spectroscopy. Furthermore, by laser scanning confocal microscopy, ZPB1 and ZPC
      were observed to colocalize on the surface of ZPC-expressing transfectants
      cultured in the presence of ZPB1, whereas almost no ZPC was detected on the
      surface of the transfectants cultured in the absence of ZPB1. Taken together,
      these results suggest that ZPB1 transported into ovarian follicles encounters and
      associates with ZPC secreted from granulosa cells, resulting in the formation of
      heterocomplexes around an oocyte. In addition, it appears that such ZPB1-ZPC
      complexes accumulated on the oocyte surface act as a scaffold for subsequent
      matrix construction events including ZPX2 association.

PMID- 17005941
TI  - Building a testis: formation of functional testis tissue after transplantation of
      isolated porcine (Sus scrofa) testis cells.
AB  - During mammalian development, morphogenesis of the testis requires the
      coordinated interplay of somatic cells to form seminiferous cords in which the
      primitive germ cells reside. These cords are the precursor of the functional male
      gonad and as such form the basis of male fertility. Cell migration during
      mammalian organogenesis and formation of complex tissues, such as the testis, are
      difficult to study in situ. Herein, we report extensive rearrangement of cells to
      regenerate complete functional testis tissue after implantation of isolated
      neonatal porcine testis cells under the skin of immunodeficient mice. Somatic
      cells and germ cells reorganized into structures that have remarkable morphologic
      and physiologic similarity to normal testis tissue, forming the endocrine and
      spermatogenic compartment of the testis. This unique in vivo system provides an
      accessible model for the study of testicular morphogenesis that could be
      especially useful in nonrodent species.

PMID- 17005940
TI  - Establishment of a functional ovine fetoplacental artery endothelial cell line
      with a prolonged life span.
AB  - To study mechanisms governing fetoplacental vascular function, we have
      established a primary ovine fetoplacental artery endothelial (OFPAE) cell line.
      These OFPAE cells produce nitric oxide (NO), proliferate, and migrate in response
      to fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor
      (VEGF). To overcome the senescence crisis that this primary OFPAE cell line will
      eventually enter, we attempted to establish a functional OFPAE cell line with a
      prolonged life span by transfecting cells with plasmids containing a neomycin
      resistance gene and a simian virus 40 gene (SV40) expressing large T (T) and
      small t (t) antigens. The OFPAE cells at passage 8 were transfected. After
      neomycin selection, the surviving OFPAE (designated SV40 OFPAE) cells were
      expanded up to passage 80. Up to passage 30, these SV40 OFPAE cells maintained a
      morphology similar to untransfected OFPAE cells. Expression of T and t antigens
      in SV40 OFPAE cells was confirmed by immunocytochemistry. These SV40 OFPAE cells
      exhibited positive uptake of acetylated low-density lipoprotein (Ac-LDL) and
      positive staining for NO synthase 3 (NOS3) and formed capillary-like tube
      structures on Matrigel. Up to passages 20-23, these SV40 OFPAE cells proliferated
      (P < 0.05) and produced (P < 0.05) NO in response to both FGF2 and VEGF.
      Moreover, this cell proliferation stimulated by FGF2 and VEGF was dose
      dependently inhibited (P < 0.05) by PD98059 (a selective mitogen-activated
      protein kinase 1 and 2 [MAP2K1/2, also termed MEK1/2] inhibitor) or by LY294002
      (a selective phosphoinositide 3-kinase [PI3K] inhibitor). These data indicate
      that SV40 OFPAE cells, at least at passage 23, retain endothelial phenotypes and
      functions similar to their parental, untransfected OFPAE cells. Thus, a
      functional OFPAE cell line with an extended life span has been successfully
      established, potentially providing a valuable cell model for studying
      fetoplacental endothelial function.

PMID- 17005942
TI  - RNase9, an androgen-dependent member of the RNase A family, is specifically
      expressed in the rat epididymis.
AB  - Members of the RNase superfamily participate in a diverse array of biological
      processes, including RNA degradation, antipathogen activities, angiogenesis, and
      digestion. In the present study, we cloned the rat RNase9 gene by in silico
      methods and genome walking based on homology to the Macaca mulatta (rhesus
      monkey) epididymal RNase9. The gene is located on chromosome 15p14, spanning two
      exons, and is clustered with other members of the RNase A superfamily. It
      contains 1279 bp and encodes 182 amino acids, including a 24-amino acid signal
      peptide, and it has unique features known from other RNases. Unlike those other
      members, the rat RNase9 mRNA was specifically expressed in the epididymis,
      especially in the caput and corpus, and exhibited an androgen-dependent
      expression pattern but was downregulated in an epididymitis animal model. The
      RNASE9 was expressed in a principal cell-specific pattern. Interestingly, most of
      the principal cells in the caput expressed the RNASE9; however, in the distal
      caput, the principal cells showed a checkerboard-like pattern of
      immunoreactivity. We also observed that the RNASE9 was bound on the acrosomal
      domain of sperm. Its potential roles in sperm maturation are discussed.

PMID- 17005943
TI  - Videos in clinical medicine. Lumbar puncture.

PMID- 17005944
TI  - Images in clinical medicine. Plantar melanoma--a false vegetant wart.

PMID- 17005945
TI  - Delaying generic competition--corporate payoffs and the future of Plavix.

PMID- 17005946
TI  - Crisis in the emergency department.

PMID- 17005947
TI  - The continuing risk of transfusion-transmitted infections.

PMID- 17005948
TI  - Sentinel-node biopsy or nodal observation in melanoma.
AB  - BACKGROUND: We evaluated the contribution of sentinel-node biopsy to outcomes in
      patients with newly diagnosed melanoma. METHODS: Patients with a primary
      cutaneous melanoma were randomly assigned to wide excision and postoperative
      observation of regional lymph nodes with lymphadenectomy if nodal relapse
      occurred, or to wide excision and sentinel-node biopsy with immediate
      lymphadenectomy if nodal micrometastases were detected on biopsy. RESULTS: Among
      1269 patients with an intermediate-thickness primary melanoma, the mean (+/-SE)
      estimated 5-year disease-free survival rate for the population was 78.3+/-1.6% in
      the biopsy group and 73.1+/-2.1% in the observation group (hazard ratio for
      recurrence[corrected], 0.74; 95% confidence interval [CI], 0.59 to 0.93;
      P=0.009). Five-year melanoma-specific survival rates were similar in the two
      groups (87.1+/-1.3% and 86.6+/-1.6%, respectively). In the biopsy group, the
      presence of metastases in the sentinel node was the most important prognostic
      factor; the 5-year survival rate was 72.3+/-4.6% among patients with tumor
      positive sentinel nodes and 90.2+/-1.3% among those with tumor-negative sentinel
      nodes (hazard ratio for death, 2.48; 95% CI, 1.54 to 3.98; P<0.001). The
      incidence of sentinel-node micrometastases was 16.0% (122 of 764 patients), and
      the rate of nodal relapse in the observation group was 15.6% (78 of 500
      patients). The corresponding mean number of tumor-involved nodes was 1.4 in the
      biopsy group and 3.3 in the observation group (P<0.001), indicating disease
      progression during observation. Among patients with nodal metastases, the 5-year
      survival rate was higher among those who underwent immediate lymphadenectomy than
      among those in whom lymphadenectomy was delayed (72.3+/-4.6% vs. 52.4+/-5.9%;
      hazard ratio for death, 0.51; 95% CI, 0.32 to 0.81; P=0.004). CONCLUSIONS: The
      staging of intermediate-thickness (1.2 to 3.5 mm) primary melanomas according to
      the results of sentinel-node biopsy provides important prognostic information and
      identifies patients with nodal metastases whose survival can be prolonged by
      immediate lymphadenectomy. (ClinicalTrials.gov number, NCT00275496
      [ClinicalTrials.gov].).

PMID- 17005950
TI  - Transmission of human herpesvirus 8 by blood transfusion.
AB  - BACKGROUND: Whether human herpesvirus 8 (HHV-8) is transmissible by blood
      transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by
      blood transfusion in Uganda, where HHV-8 is endemic. METHODS: We enrolled
      patients in Kampala, Uganda, who had received blood transfusions between December
      2000 and October 2001. Pretransfusion and multiple post-transfusion blood
      specimens from up to nine visits over a 6-month period were tested for HHV-8
      antibody. We calculated the excess risk of seroconversion over time among
      recipients of HHV-8-seropositive blood as compared with recipients of
      seronegative blood. RESULTS: Of the 1811 transfusion recipients enrolled, 991
      were HHV-8-seronegative before transfusion and completed the requisite follow-up,
      43% of whom received HHV-8-seropositive blood and 57% of whom received
      seronegative blood. HHV-8 seroconversion occurred in 41 of the 991 recipients.
      The risk of seroconversion was significantly higher among recipients of HHV-8
      seropositive blood than among recipients of seronegative blood (excess risk,
      2.8%; P<0.05), and the increase in risk was seen mainly among patients in whom
      seroconversion occurred 3 to 10 weeks after transfusion (excess risk, 2.7%;
      P=0.005), a result consistent with the transmission of the virus by transfusion.
      Blood units stored for up to 4 days were more often associated with
      seroconversion than those stored for more than 4 days (excess risk, 4.2%;
      P<0.05). CONCLUSIONS: This study provides strong evidence that HHV-8 is
      transmitted by blood transfusion. The risk may be diminished as the period of
      blood storage increases.

PMID- 17005949
TI  - International trial of the Edmonton protocol for islet transplantation.
AB  - BACKGROUND: Islet transplantation offers the potential to improve glycemic
      control in a subgroup of patients with type 1 diabetes mellitus who are disabled
      by refractory hypoglycemia. We conducted an international, multicenter trial to
      explore the feasibility and reproducibility of islet transplantation with the use
      of a single common protocol (the Edmonton protocol). METHODS: We enrolled 36
      subjects with type 1 diabetes mellitus, who underwent islet transplantation at
      nine international sites. Islets were prepared from pancreases of deceased donors
      and were transplanted within 2 hours after purification, without culture. The
      primary end point was defined as insulin independence with adequate glycemic
      control 1 year after the final transplantation. RESULTS: Of the 36 subjects, 16
      (44%) met the primary end point, 10 (28%) had partial function, and 10 (28%) had
      complete graft loss 1 year after the final transplantation. A total of 21
      subjects (58%) attained insulin independence with good glycemic control at any
      point throughout the trial. Of these subjects, 16 (76%) required insulin again at
      2 years; 5 of the 16 subjects who reached the primary end point (31%) remained
      insulin-independent at 2 years. CONCLUSIONS: Islet transplantation with the use
      of the Edmonton protocol can successfully restore long-term endogenous insulin
      production and glycemic stability in subjects with type 1 diabetes mellitus and
      unstable control, but insulin independence is usually not sustainable. Persistent
      islet function even without insulin independence provides both protection from
      severe hypoglycemia and improved levels of glycated hemoglobin.
      (ClinicalTrials.gov number, NCT00014911 [ClinicalTrials.gov].).

PMID- 17005951
TI  - American medical education 100 years after the Flexner report.

PMID- 17005952
TI  - The tuberous sclerosis complex.

PMID- 17005953
TI  - Images in clinical medicine. Intratracheal melanoma metastases.

PMID- 17005954
TI  - Case records of the Massachusetts General Hospital. Case 30-2006. A 41-year-old
      man with dyspnea, fever, and lymphadenopathy.

PMID- 17005955
TI  - Sentinel-node biopsy in melanoma.

PMID- 17005956
TI  - Diabetes cure--is the glass half full?

PMID- 17005959
TI  - Hunger strikes at Guantanamo--medical ethics and human rights in a "legal black
      hole".

PMID- 17005960
TI  - Key role for a viral lytic gene in Kaposi's sarcoma.

PMID- 17005961
TI  - Treatment of gastric cancer.

PMID- 17005962
TI  - Condom use and the risk of HPV infection.

PMID- 17005963
TI  - Homocysteine lowering and cognitive performance.

PMID- 17005964
TI  - Retinol-binding protein 4 and insulin resistance.

PMID- 17005965
TI  - Molecular mechanisms in melanoma.

PMID- 17005966
TI  - Alemtuzumab for refractory celiac disease.

PMID- 17005967
TI  - Autoimmunity after islet-cell allotransplantation.

PMID- 17005968
TI  - Different subcellular locations of secretome components of Gram-positive
      bacteria.
AB  - Gram-positive bacteria contain different types of secretion systems for the
      transport of proteins into or across the cytoplasmic membrane. Recent studies on
      subcellular localization of specific components of these secretion systems and
      their substrates have shown that they can be present at various locations in the
      cell. The translocons of the general Sec secretion system in the rod-shaped
      bacterium Bacillus subtilis have been shown to localize in spirals along the
      cytoplasmic membrane, whereas the translocons in the coccoid Streptococcus
      pyogenes are located in a microdomain near the septum. In both bacteria the Sec
      translocons appear to be located near the sites of cell wall synthesis. The Tat
      secretion system, which is used for the transport of folded proteins, probably
      localizes in the cytoplasmic membrane and at the cell poles of B. subtilis. In
      Lactococcus lactis the ABC transporter dedicated to the transport of a small
      antimicrobial peptide is distributed throughout the membrane. Possible mechanisms
      for maintaining the localization of these secretion machineries involve their
      interaction with proteins of the cytoskeleton or components of the cell wall
      synthesis machinery, or the presence of lipid subdomains surrounding the
      transport systems.

PMID- 17005969
TI  - A mannose-sensitive haemagglutinin (MSHA)-like pilus promotes attachment of
      Pseudoalteromonas tunicata cells to the surface of the green alga Ulva australis.
AB  - This study demonstrates that attachment of the marine bacterium Pseudoalteromonas
      tunicata to the cellulose-containing surface of the green alga Ulva australis is
      mediated by a mannose-sensitive haemagglutinin (MSHA-like) pilus. We have
      identified an MSHA pilus biogenesis gene locus in P. tunicata, termed
      msh/1/2JKLMNEGFBACDOPQ, which shows significant homology, with respect to its
      genetic characteristics and organization, to the MSHA pilus biogenesis gene locus
      of Vibrio cholerae. Electron microscopy studies revealed that P. tunicata wild
      type cells express flexible pili peritrichously arranged on the cell surface. A
      P. tunicata mutant (SM5) with a transposon insertion in the mshJ region displayed
      a non-piliated phenotype. Using SM5, it has been demonstrated that the MSHA pilus
      promotes attachment of P. tunicata wild-type cells in polystyrene microtitre
      plates, as well as to microcrystalline cellulose and to the living surface of U.
      australis. P. tunicata also demonstrated increased pilus production in response
      to cellulose and its monomer constituent cellobiose. The MSHA pilus thus
      functions as a determinant of attachment in P. tunicata, and it is proposed that
      an understanding of surface sensing mechanisms displayed by P. tunicata will
      provide insight into specific ecological interactions that occur between this
      bacterium and higher marine organisms.

PMID- 17005970
TI  - Amino acids mediate colony and cell differentiation in the fungal pathogen
      Candida parapsilosis.
AB  - Candida parapsilosis is responsible for severe cases of non-albicans systemic
      candidiasis and is one of the leading causes of mortality in neonates. The
      molecular mechanisms underlying this organism's virulence remain unknown. Unlike
      C. albicans, which can exist in several morphogenetic forms, C. parapsilosis
      exists in either the yeast or pseudohyphal forms. The environmental signals that
      trigger pseudohyphal differentiation and the signalling pathways that transduce
      these signals are unknown. This paper provides evidence for the role of amino
      acids in morphogenesis in C. parapsilosis. The cell and colony morphologies,
      pseudohyphal differentiation and invasive growth of five C. parapsilosis isolates
      were characterized in ammonium-rich minimal media lacking or supplemented with
      naturally occurring amino acids. C. parapsilosis underwent dramatic changes in
      cellular and colony morphology and formed pseudohyphae in response to a specific
      subset of amino acids. Transport studies showed that these amino acid inducers
      activate the transport of some, but not all, unrelated amino acids.
      Interestingly, citrulline, an amino acid that is not transported in the presence
      of ammonium, strongly induced pseudohyphal morphogenesis in C. parapsilosis under
      these conditions. Together the data suggest that amino acids are important
      morphogens in C. parapsilosis and that amino-acid-mediated morphogenesis in this
      organism does not require transport of the ligand across the plasma membrane.

PMID- 17005971
TI  - Functional analysis of 11 putative essential genes in Bacillus subtilis.
AB  - Systematic inactivation of Bacillus subtilis genes has previously revealed that
      271 are indispensable for growth. In the present study, 11 of these (yacA, ydiB,
      ydiC, ykqC, ylaN, yloQ, ymdA, yneS, yqeI, yqjK and ywlC) were identified as genes
      encoding proteins of unknown function. By analysing the effects of protein
      depletion, and examining the subcellular localization of these proteins, a start
      has been made in elucidating their functions. It was found that four of these
      genes (ydiB, yloQ, yqeI and ywlC) were not required for B. subtilis viability.
      Analysis of the localization of YkqC suggests that it co-localizes with
      ribosomes, and it is proposed that it is involved in processing either rRNA or
      specific mRNAs when they are associated with the ribosome. The results suggest
      that other novel essential proteins may be involved in lipid synthesis and
      control of cell wall synthesis.

PMID- 17005972
TI  - Contribution of alginate and levan production to biofilm formation by Pseudomonas
      syringae.
AB  - Exopolysaccharides (EPSs) play important roles in the attachment of bacterial
      cells to a surface and/or in building and maintaining the three-dimensional,
      complex structure of bacterial biofilms. To elucidate the spatial distribution
      and function of the EPSs levan and alginate during biofilm formation, biofilms of
      Pseudomonas syringae strains with different EPS patterns were compared. The
      mucoid strain PG4180.muc, which produces levan and alginate, and its levan-
      and/or alginate-deficient derivatives all formed biofilms in the wells of
      microtitre plates and in flow chambers. Confocal laser scanning microscopy with
      fluorescently labelled lectins was applied to investigate the spatial
      distribution of levan and an additional as yet unknown EPS in flow-chamber
      biofilms. Concanavalin A (ConA) bound specifically to levan and accumulated in
      cell-depleted voids in the centres of microcolonies and in blebs. No binding of
      ConA was observed in biofilms of the levan-deficient mutants or in wild-type
      biofilms grown in the absence of sucrose as confirmed by an enzyme-linked lectin
      sorbent assay using peroxidase-linked ConA. Time-course studies revealed that
      expression of the levan-forming enzyme, levansucrase, occurred mainly during
      early exponential growth of both planktonic and sessile cells. Thus, accumulation
      of levan in biofilm voids hints to a function as a nutrient storage source for
      later stages of biofilm development. The presence of a third EPS besides levan
      and alginate was indicated by binding of the lectin from Naja mossambica to a
      fibrous structure in biofilms of all P. syringae derivatives. Production of the
      as yet uncharacterized additional EPS might be more important for biofilm
      formation than the syntheses of levan and alginate.

PMID- 17005973
TI  - Inhibitors of Helicobacter pylori ATPase Cagalpha block CagA transport and cag
      virulence.
AB  - With the steadily increasing occurrence of antibiotic resistance in bacteria,
      there is a great need for new antibacterial compounds. The approach described
      here involves targeting virulence-related bacterial type IV secretion systems
      (TFSSs) with small-molecule inhibitors. The cag TFSS of Helicobacter pylori was
      chosen as a model, and novel inhibitors directed against the cag VirB11-type
      ATPase Cagalpha were identified. The cag genes encode proteins that are
      components of a contact-dependent secretion system used by the bacterium to
      translocate the effector molecule CagA into host cells. Translocated CagA is
      associated with severe gastritis, and carcinoma. Furthermore, functional TFSSs
      and immunodominant CagA play a role in interleukin (IL)-8 induction, which is an
      important factor for chronic inflammation. Inhibitors of Cagalpha were identified
      by high-throughput screening of chemical libraries that comprised 524 400 small
      molecules. The ATPase activity of Cagalpha was inhibited by the selected
      compounds in an in vitro enzymic assay using the purified enzyme. The most active
      compound, CHIR-1, reduced TFSS function to an extent that cellular effects on AGS
      cells mediated by CagA were virtually undetectable, while reduced levels of IL-8
      induction were observed. Gastric colonization by CHIR-1-pre-treated bacteria was
      found to be impaired in a dose-dependent manner using a mouse model of infection.
      Small-molecule Cagalpha inhibitors, the first described inhibitors of a TFSS, are
      potential candidates for the development of new antibacterial compounds that may
      lead to alternative medical treatments. The compounds are expected to impose weak
      selective pressure, since they target virulence functions. Moreover, the targeted
      virulence protein is conserved in a variety of bacterial pathogens. Additionally,
      TFSS inhibitors are potent tools to study the biology of TFSSs.

PMID- 17005974
TI  - Duplication of the mmoX gene in Methylosinus sporium: cloning, sequencing and
      mutational analysis.
AB  - The soluble methane monooxygenase (sMMO) is a key enzyme for methane oxidation,
      and is found in only some methanotrophs, including Methylosinus sporium 5. sMMO
      expression is regulated at the level of transcription from a sigma(54) promoter
      by a copper-switch, and is only expressed when the copper-to-biomass ratio during
      growth is low. Extensive phylogenetic and genetic analyses of sMMOs and other
      soluble di-iron monooxygenases reveal that these enzymes have only been acquired
      relatively recently through horizontal gene transfer. In this study, further
      evidence of horizontal gene transfer was obtained, through cloning and sequencing
      of the genes encoding the sMMO enzyme complex plus the regulatory genes mmoG and
      mmoR, and identification of a duplicate copy of the mmoX gene in Ms. sporium.
      mmoX encodes the alpha subunit of the hydroxylase of the sMMO enzyme, which
      constitutes the active site (Prior & Dalton, 1985). The mmoX genes were
      characterized at the molecular and biochemical levels. Although both copies were
      transcribed, only mmoX copy 1 was essential for sMMO activity. Construction of an
      sMMO(-) mutant by marker-exchange mutagenesis gave some possible insights into
      the role of the water-soluble pigment in siderophore-mediated iron acquisition.
      Finally, the amenability of Ms. sporium to genetic manipulation was demonstrated
      by complementing the sMMO(-) mutant by heterologous expression of sMMO genes from
      Methylosinus trichosporium OB3b and Methylococcus capsulatus (Bath), and it was
      shown that Ms. sporium could be used as an alternative model organism for
      molecular analysis of MMO regulation.

PMID- 17005975
TI  - RepAM of the Amycolatopsis methanolica integrative element pMEA300 belongs to a
      novel class of replication initiator proteins.
AB  - Accessory genetic elements, such as plasmids and integrative elements, are
      widespread amongst actinomycetes, but little is known about their functions and
      mode of replication. The conjugative element pMEA300 from Amycolatopsis
      methanolica is present mostly in an integrated state at a single specific site in
      the chromosome, but it can also replicate autonomously. Complete nucleotide
      sequencing, in combination with deletion studies, has revealed that orfB of
      pMEA300 is essential for autonomous replication in its host. In this study, it
      was shown that purified OrfB protein binds specifically to the 3' end of its own
      coding sequence. Within this short sequence, a putative hairpin structure is
      located, which contains several direct and inverted repeats, and a nucleotide
      stretch that resembles the nicking site of the pC194 family of rolling circle
      replicating plasmids. Additional binding studies revealed that OrfB binds to an 8
      bp inverted repeat that occurs three times within the hairpin structure. The data
      presented show that OrfB is the replication initiator (Rep) protein of pMEA300,
      and is therefore termed RepAM. Surprisingly, RepAM lacks significant sequence
      similarity with known prokaryotic Rep proteins, but it is highly similar to a
      number of yet uncharacterized ORFs that are located on integrative and
      conjugative elements of other actinomycetes. It is concluded that RepAM and its
      homologues are members of a novel class of Rep proteins.

PMID- 17005976
TI  - The role of the histidine-35 residue in the cytocidal action of HM-1 killer
      toxin.
AB  - Diethylpyrocarbonate modification and site-directed mutagenesis studies of
      histidine-35 in HM-1 killer toxin (HM-1) have shown that a specific feature, the
      imidazole side chain of histidine-35, is essential for the expression of the
      killing activity. In subcellular localization experiments, wild-type HM-1 was in
      the membrane fraction of Saccharomyces cerevisiae BJ1824, but not the HM-1
      analogue in which histidine-35 was replaced by alanine (H35A HM-1). Neither wild
      type nor H35A HM-1 was detected in cellular fractions of HM-1-resistant yeast S.
      cerevisiae BJ1824 rhk1Delta : : URA3 and HM-1-insensitive yeast Candida albicans
      even after 1 h incubation. H35A HM-1 inhibited the activity of partially purified
      1,3-beta-glucan synthase from S. cerevisiae A451, and its extent was almost the
      same as wild-type HM-1. Co-immunoprecipitation experiments showed that wild-type
      and H35A HM-1 directly interact with the 1,3-beta-glucan synthase complex. These
      results strongly suggest that histidine-35 has an important role in the cytocidal
      action of HM-1 that participates in the binding process to the HM-1 receptor
      protein on the cell membrane, but it is not essential for the interaction with,
      and inhibition of, 1,3-beta-glucan synthase.

PMID- 17005977
TI  - Interaction of the transmembrane domain of lysis protein E from bacteriophage
      phiX174 with bacterial translocase MraY and peptidyl-prolyl isomerase SlyD.
AB  - The molecular target for the bacteriolytic E protein from bacteriophage X174,
      responsible for host cell lysis, is known to be the enzyme phospho-MurNAc
      pentapeptide translocase (MraY), an integral membrane protein involved in
      bacterial cell wall peptidoglycan biosynthesis, with an essential role being
      played by peptidyl-prolyl isomerase SlyD. A synthetic 37 aa peptide E(pep),
      containing the N-terminal transmembrane alpha-helix of E, was found to be
      bacteriolytic against Bacillus licheniformis, and inhibited membrane-bound MraY.
      The solution conformation of E(pep) was found by circular dichroism (CD)
      spectroscopy to be 100 % alpha-helical. No change in the CD spectrum was observed
      upon addition of purified Escherichia coli SlyD, implying that SlyD does not
      catalyse prolyl isomerization upon E. However, E(pep) was found to be a potent
      inhibitor of SlyD-catalysed peptidyl-prolyl isomerization (IC(50) 0.15 microM),
      implying a strong interaction between E and SlyD. E(pep) was found to inhibit E.
      coli MraY activity when assayed in membranes (IC(50) 0.8 microM); however, no
      inhibition of solubilized MraY was observed, unlike nucleoside natural product
      inhibitor tunicamycin. These results imply that the interaction of E with MraY is
      not at the MraY active site, and suggest that a protein-protein interaction is
      formed between E and MraY at a site within the transmembrane region.

PMID- 17005978
TI  - The enduracidin biosynthetic gene cluster from Streptomyces fungicidicus.
AB  - The biosynthetic gene cluster for the 17 aa peptide antibiotic enduracidin has
      been cloned and sequenced from Streptomyces fungicidicus ATCC 21013. The 84 kb
      gene cluster contains 25 ORFs and is located within a 116 kb genetic locus that
      was fully sequenced. Targeted disruption of non-ribosomal peptide synthetase
      (NRPS) genes in the cluster abolished enduracidin production and confirmed
      function. The cluster includes four genes, endA-D, encoding two-, seven-, eight-
      and one-module NRPSs, respectively, and includes unique modules for the
      incorporation of citrulline and enduracididine. The NRPS organization generally
      follows the collinearity principle, and starts with a condensation domain (C
      domain) similar to those found in other lipopeptide systems for the coupling of
      an acyl group to the starting amino acid. The sixth module of EndB, corresponding
      to Thr(8), is missing an adenylation domain (A domain) and this module is
      presumed to be loaded in trans by the single module protein EndD. The most
      striking feature of the NRPS organization is the lack of epimerization domains (E
      domains) in light of the fact that the product has seven d-amino acid residues.
      Sequence analysis reveals that C domains following modules corresponding to d
      amino acids belong to a unique subset of C domains able to catalyse both
      epimerization and condensation reactions. Other genes directing lipid
      modification and activation, and formation of the non-proteinogenic amino acids 4
      hydroxyphenylglycine and enduracididine are readily identified, as are genes
      possibly involved in regulation of antibiotic biosynthesis and export. These
      findings provide the basis to further genetically manipulate and improve
      lipodepsipeptide antibiotics via combinatorial and chemical methods.

PMID- 17005979
TI  - Stimulation of the lambda pR promoter by Escherichia coli SeqA protein requires
      downstream GATC sequences and involves late stages of transcription initiation.
AB  - Escherichia coli SeqA protein is a major negative regulator of chromosomal DNA
      replication acting by sequestration, and thus inactivation, of newly formed oriC
      regions. However, other activities of this protein have been discovered recently,
      one of which is regulation of transcription. SeqA has been demonstrated to be a
      specific transcription factor acting at bacteriophage lambda promoters p(I),
      p(aQ) and p(R). While SeqA-mediated stimulation of p(I) and p(aQ) occurs by
      facilitating functions of another transcription activator protein, cII, a
      mechanism for stimulation of p(R) remains largely unknown. Here, it has been
      demonstrated that two GATC sequences, located 82 and 105 bp downstream of the
      p(R) transcription start site, are necessary for this stimulation both in vivo
      and in vitro. SeqA-mediated activation of p(R) was as effective on a linear DNA
      template as on a supercoiled one, indicating that alterations in DNA topology are
      not likely to facilitate the SeqA effect. In vitro transcription analysis
      demonstrated that the most important regulatory effect of SeqA in p(R)
      transcription occurs after open complex formation, namely during promoter
      clearance. SeqA did not influence the appearance and level of abortive
      transcripts or the pausing during transcription elongation. Interestingly, SeqA
      is one of few known prokaryotic transcription factors which bind downstream of
      the regulated promoter and still act as transcription activators.

PMID- 17005980
TI  - Complementation of daptomycin dptA and dptD deletion mutations in trans and
      production of hybrid lipopeptide antibiotics.
AB  - Daptomycin is a lipopeptide antibiotic produced by Streptomyces roseosporus and
      recently commercialized as Cubicin (daptomycin-for-injection) for treatment of
      skin and skin-structure infections caused by Gram-positive pathogens. Daptomycin
      is synthesized by a non-ribosomal peptide synthetase (NRPS) encoded by three
      overlapping genes, dptA, dptBC and dptD. The dptE and dptF genes, immediately
      upstream of dptA, are likely to be involved in the initiation of daptomycin
      biosynthesis by coupling decanoic acid to the N-terminal Trp. Analysis of RT-PCR
      data suggests that dptE, dptF, dptA, dptBC, dptD and possibly other dpt genes are
      transcribed as one large message; however, it has been demonstrated that
      sequential translation of these genes from a long transcript is not essential for
      robust daptomycin production. The dptA and the dptD genes were deleted from the
      dpt gene cluster, and expressed from ectopic positions in the chromosome under
      the control of the strong constitutive ermEp* promoter to produce high levels of
      lipopeptides. This three-locus trans-complementation system was used to produce
      hybrid lipopeptide antibiotics by introducing the heterologous lptD and cdaPS3
      genes from Streptomyces fradiae and Streptomyces coelicolor, respectively, to
      complement the DeltadptD mutation.

PMID- 17005981
TI  - Ecophysiology of different filamentous Alphaproteobacteria in industrial
      wastewater treatment plants.
AB  - The ecophysiology of five filamentous species affiliated to the
      Alphaproteobacteria was investigated in industrial activated sludge systems. The
      five species, 'Candidatus Alysiosphaera europaea', 'Candidatus Monilibacter
      batavus', 'Candidatus Alysiomicrobium bavaricum', 'Candidatus Sphaeronema
      italicum' and Meganema perideroedes, are very abundant in industrial wastewater
      treatment plants and are often involved in bulking incidents. The morphology of
      these filamentous bacterial species resembled Eikelboom's Nostocoida limicola, or
      Type 021N, and could only be correctly identified by using fluorescence in situ
      hybridization (FISH), applying species-specific gene probes. Two physiological
      groupings of the five species were found using microautoradiography combined with
      FISH. Group 1 ('Ca. Monilibacter batavus' and 'Ca. Sphaeronema italicum')
      utilized many short-chained fatty acids (acetate, pyruvate and propionate),
      whereas Group 2 ('Ca. Alysiosphaera europaea', 'Ca. Alysiomicrobium bavaricum'
      and Meganema perideroedes) could also exploit several sugars, amino acids and
      ethanol. All species had polyhydroxyalkanoate granules present and several of the
      species had a very large storage capacity. No activity was found under strict
      anaerobic conditions, while uptake of substrate was observed in the presence of
      nitrate or nitrite as potential electron acceptor. However, for all species a
      reduced number of substrates could be consumed under these conditions compared to
      aerobic conditions. Only a little exo-enzymic activity was found and nearly all
      species had a hydrophobic cell surface. Based on knowledge of the
      ecophysiological potential, control strategies are suggested.

PMID- 17005982
TI  - Diversity of culturable halophilic sulfur-oxidizing bacteria in hypersaline
      habitats.
AB  - Unexpectedly high culturable diversity of moderately and extremely halophilic
      obligately chemolithoautotrophic sulfur-oxidizing bacteria (SOB) was discovered
      in the sediments of various hypersaline habitats, including chloride-sulfate
      lakes in Mongolia, Russia and Ukraine, a sea saltern in Slovenia and a deep-sea
      salt brine from the Mediterranean. Six different groups of halophilic SOB,
      including four new genera, all belonging to the Gammaproteobacteria, were found.
      Two groups of moderately halophilic strictly aerobic SOB dominated at 2 M NaCl,
      including representatives of the genus Halothiobacillus (in fully aerobic
      conditions) and Thiomicrospira (in micro-oxic conditions). Under denitrifying
      conditions at 2 M NaCl, a group of moderately halophilic and facultatively
      anaerobic SOB was selected, capable of complete denitrification of nitrate. The
      group represents a new genus with closest relatives among as yet undescribed
      marine thiodenitrifying isolates. With thiocyanate as a substrate, an enrichment
      culture at 2 M NaCl yielded a pure culture of moderately halophilic SOB capable
      of aerobic growth with thiocyanate and thiosulfate at up to 4 M NaCl.
      Furthermore, this bacterium also grew anaerobically using nitrite as electron
      acceptor. It formed a new lineage distantly related to the genus Thiomicrospira.
      Enrichments at 4 M NaCl resulted in the domination of two different, previously
      unknown, groups of extremely halophilic SOB. Under oxic conditions, they were
      represented by strictly aerobic spiral-shaped bacteria, related to the
      Ectothiorhodospiraceae, while under denitrifying conditions a group of
      facultatively anaerobic nitrate-reducing bacteria with long rod-shaped cells was
      selected, distantly related to the genus Acidithiobacillus.

PMID- 17005983
TI  - Dual regulation of a polyethylene glycol degradative operon by AraC-type and GalR
      type regulators in Sphingopyxis macrogoltabida strain 103.
AB  - The genes for polyethylene glycol (PEG) catabolism (pegB, C, D, A and E) in
      Sphingopyxis macrogoltabida strain 103 were shown to form a PEG-inducible operon.
      The pegR gene, encoding an AraC-type regulator in the downstream area of the
      operon, is transcribed in the reverse direction. The transcription start sites of
      the operon were mapped, and three putative sigma(70)-type promoter sites were
      identified in the pegB, pegA and pegR promoters. A promoter activity assay showed
      that the pegB promoter was induced by PEG and oligomeric ethylene glycols,
      whereas the pegA and pegR promoters were induced by PEG. Deletion analysis of the
      pegB promoter indicated that the region containing the activator-binding motif of
      an AraC/XylS-type regulator was required for transcription of the pegBCDAE
      operon. Gel retardation assays demonstrated the specific binding of PegR to the
      pegB promoter. Transcriptional fusion studies of pegR with pegA and pegB
      promoters suggested that PegR regulates the expression of the pegBCDAE operon
      positively through its binding to the pegB promoter, but PegR does not bind to
      the pegA promoter. Two specific binding proteins for the pegA promoter were
      purified and identified as a GalR-type regulator and an H2A histone fragment
      (histone-like protein, HU). The binding motif of a GalR/LacI-type regulator was
      found in the pegA and pegR promoters. These results suggested the dual regulation
      of the pegBCDAE operon through the pegB promoter by an AraC-type regulator, PegR
      (PEG-independent), and through the pegA and pegR promoters by a GalR/LacI-type
      regulator together with HU (PEG-dependent).

PMID- 17005984
TI  - Comparative analysis of two-component signal transduction systems of Bacillus
      cereus, Bacillus thuringiensis and Bacillus anthracis.
AB  - Members of the Bacillus cereus group are ubiquitously present in the environment
      and can adapt to a wide range of environmental fluctuations. In bacteria, these
      adaptive responses are generally mediated by two-component signal transduction
      systems (TCSs), which consist of a histidine kinase (HK) and its cognate response
      regulator (RR). With the use of in silico techniques, a complete set of HKs and
      RRs was recovered from eight completely sequenced B. cereus group genomes. By
      applying a bidirectional best-hits method combined with gene neighbourhood
      analysis, a footprint of these proteins was made. Around 40 HK-RR gene pairs were
      detected in each member of the B. cereus group. In addition, each member
      contained many HK and RR genes not encoded in pairs ("orphans"). Classification
      of HKs and RRs based on their enzymic domains together with the analysis of two
      neighbour-joining trees of these domains revealed putative interaction partners
      for most of the "orphans". Putative biological functions, including involvement
      in virulence and host-microbe interactions, were predicted for the B. cereus
      group HKs and RRs by comparing them with those of B. subtilis and other micro
      organisms. Remarkably, B. anthracis appeared to lack specific HKs and RRs and was
      found to contain many truncated, putatively non-functional, HK and RR genes. It
      is hypothesized that specialization of B. anthracis as a pathogen could have
      reduced the range of environmental stimuli to which it is exposed. This may have
      rendered some of its TCSs obsolete, ultimately resulting in the deletion of some
      HK and RR genes.

PMID- 17005985
TI  - The Sinorhizobium medicae WSM419 lpiA gene is transcriptionally activated by FsrR
      and required to enhance survival in lethal acid conditions.
AB  - Sinorhizobium medicae WR101 was identified as a mutant of WSM419 that contained a
      minitransposon-induced transcriptional gusA fusion activated at least 20-fold at
      pH 5.7. The expression of this fusion in moderately acid conditions was dependent
      on the calcium concentration; increasing the calcium concentration to enhance
      cell growth and survival in acid conditions decreased the expression of the
      fusion. A gene region containing the gusA fusion was sequenced, revealing five S.
      medicae genes: tcsA, tcrA, fsrR, lpiA and acvB. The gusA reporter in WR101 was
      fused to lpiA, which encodes a putative transmembrane protein also found in other
      Alphaproteobacteria such as Sinorhizobium meliloti, Rhizobium tropici and
      Agrobacterium tumefaciens. As LpiA has partial sequence similarity to the lysyl
      phosphatidylglycerol (LPG) synthetase FmtC/MprF from Staphylococcus aureus,
      membrane lipid compositions of S. medicae strains were analysed. Cells cultured
      under neutral or acidic growth conditions did not induce any detectable LPG and
      therefore this lipid cannot be a major constituent of S. medicae membranes.
      Expression studies in S. medicae localized the acid-activated lpiA promoter
      within a 372 bp region upstream of the start codon. The acid-activated
      transcription of lpiA required the fused sensor-regulator product of the fsrR
      gene, because expression of lpiA was severely reduced in an S. medicae fsrR
      mutant. S. meliloti strain 1021 does not contain fsrR and acid-activated
      expression of the lpiA-gusA fusion did not occur in this species. Although acid
      activated lpiA transcription was not required for cell growth, its expression was
      crucial in enhancing the viability of cells subsequently exposed to lethal acid
      (pH 4.5) conditions.

PMID- 17005986
TI  - Database mining and transcriptional analysis of genes encoding inulin-modifying
      enzymes of Aspergillus niger.
AB  - As a soil fungus, Aspergillus niger can metabolize a wide variety of carbon
      sources, employing sets of enzymes able to degrade plant-derived polysaccharides.
      In this study the genome sequence of A. niger strain CBS 513.88 was surveyed, to
      analyse the gene/enzyme network involved in utilization of the plant storage
      polymer inulin, and of sucrose, the substrate for inulin synthesis in plants. In
      addition to three known activities, encoded by the genes suc1 (invertase
      activity; designated sucA), inuE (exo-inulinase activity) and inuA/inuB (endo
      inulinase activity), two new putative invertase-like proteins were identified.
      These two putative proteins lack N-terminal signal sequences and therefore are
      expected to be intracellular enzymes. One of these two genes, designated sucB, is
      expressed at a low level, and its expression is up-regulated when A. niger is
      grown on sucrose- or inulin-containing media. Transcriptional analysis of the
      genes encoding the sucrose- (sucA) and inulin-hydrolysing enzymes (inuA and inuE)
      indicated that they are similarly regulated and all strongly induced on sucrose
      and inulin. Analysis of a DeltacreA mutant strain of A. niger revealed that
      expression of the extracellular inulinolytic enzymes is under control of the
      catabolite repressor CreA. Expression of the inulinolytic enzymes was not induced
      by fructose, not even in the DeltacreA background, indicating that fructose did
      not act as an inducer. Evidence is provided that sucrose, or a sucrose-derived
      intermediate, but not fructose, acts as an inducer for the expression of
      inulinolytic genes in A. niger.

PMID- 17005987
TI  - Transcriptional profiling of a Staphylococcus aureus clinical isolate and its
      isogenic agr and sarA mutants reveals global differences in comparison to the
      laboratory strain RN6390.
AB  - The production of Staphylococcus aureus virulence factors is under the control of
      complex regulatory circuits. Most studies aimed at defining these regulatory
      networks have focused on derivatives of the strain NCTC 8325, most notably
      RN6390. However, all NCTC 8325 derivatives, including RN6390, possess an 11 bp
      deletion in rsbU. This deletion renders NCTC 8325 derivatives naturally sigma
      factor-B deficient. Recent studies have shown that RN6390 is also deficient, in
      comparison to clinical isolates, with respect to biofilm formation, a process
      which is important for both pathogenesis and antimicrobial resistance. Based on
      these considerations, the authors carried out genome-scale transcriptional
      profiling, comparing RN6390 with the virulent rsbU-positive clinical isolate UAMS
      1. The results revealed significant genome-wide differences in expression
      patterns between RN6390 and UAMS-1, and suggested that the overall
      transcriptional profile of UAMS-1 is geared toward expression of factors that
      promote colonization and biofilm formation. In contrast, the transcriptional
      profile of RN6390 was heavily influenced by RNAIII expression, resulting in a
      phenotype characterized by increased production of exoproteins, and decreased
      capacity to form a biofilm. The greater influence of agr in RN6390 relative to
      UAMS-1 was also evident when the transcriptional profile of UAMS-1 was compared
      with that of its isogenic sarA and agr mutants. Specifically, the results
      indicate that, in contrast to NCTC 8325 derivatives, agr plays a limited role in
      overall regulation of gene expression in UAMS-1, when compared with sarA.
      Furthermore, by defining the sarA regulon in a biofilm-positive clinical isolate,
      and comparing the results with transcriptional profiling experiments defining
      biofilm-associated gene expression patterns in the same strain, the authors
      identified a sarA-regulated operon (alsSD) that is also induced in biofilms, and
      demonstrated that mutation of alsSD results in reduced capacity to form a
      biofilm.

PMID- 17005988
TI  - A truncated Bacillus subtilis dal gene with a 3' ssrA gene tag regulates the
      growth and virulence of racemase-deficient Listeria monocytogenes.
AB  - Listeria monocytogenes (Lm) is a Gram-positive intracellular pathogen that can
      elicit strong cellular immunity. An attenuated strain (Lmdd) with deletions in
      two genes (dal and dat) required for d-alanine synthesis and viability has been
      shown to induce long-lived protective systemic and mucosal immune responses in
      mice when administered in the presence of the required amino acid. To bypass the
      necessity for exogenous d-alanine without compromising the safety of the original
      strain, the defect of Lmdd was complemented with a heterologous Bacillus subtilis
      dal gene, and the effects of truncating the upstream region of the gene on its
      transcription efficiency and of modifying its protein product with an ssrA tag at
      the 3'-terminus were examined. The strains with 551 bp and 80 bp upstream regions
      showed high levels of transcription and grew without d-alanine. The strains with
      the shortest upstream regions, 48 bp and 18 bp, showed greatly decreased levels
      of transcription and failed to grow in the absence of d-alanine. Addition of an
      ssrA tag to the longer genes resulted in a somewhat altered growth pattern in
      media and a reduced plaque size on L2 fibroblasts. These bacteria contained low
      levels of racemase protein and reduced free pools of d-alanine. One of the
      strains tested further, Lmdd/pA80S, was rapidly cleared from the spleens of
      infected mice but nevertheless induced a strong immune response that protected
      mice against challenge by wild-type L. monocytogenes. These bacteria can thus
      induce immune responses in mice comparable to the original Lmdd strain, but
      without the need for exogenous d-alanine, and may have use as a live vaccine
      vector against infectious diseases and cancers.

PMID- 17005989
TI  - Significant passive protective effect against anthrax by antibody to Bacillus
      anthracis inactivated spores that lack two virulence plasmids.
AB  - The protective-antigen (PA)-based cell-free vaccine is the only vaccine licensed
      for use against Bacillus anthracis infection in humans. Although the PA shows
      strong immunogenicity, the capsule or spore-associated somatic antigens may be
      important as additional vaccine targets for full protection against anthrax. In
      this study, the protective effect of spore-associated antigens against B.
      anthracis infection was determined. Rabbits were immunized with formalin-fixed
      spores of a non-toxigenic unencapsulated B. anthracis strain that lacked the two
      virulence plasmids pXO1 and pXO2, and the protective effects of the immune
      antibody were evaluated. Immunostaining and Western blot analysis revealed that
      the anti-B. anthracis (anti-BA)-spore IgG specifically bound to the surface of
      spores or endospores of B. anthracis, but not to vegetative cells, or closely
      related Bacillus species, such as Bacillus cereus, Bacillus subtilis and Bacillus
      thuringiensis. Passively transferred anti-BA-spore IgG protected mice from
      intraperitoneal challenge with a lethal dose of fully virulent B. anthracis
      spores, and increased the survival rate in a dose-dependent manner. Pre
      incubation of spores with antibody also reduced their infectivity in a dose
      dependent manner. The number of bacteria (c.f.u.) in spleens and livers of
      infected mice was significantly lower in antibody-treated mice than in untreated
      mice. Treatment with anti-BA-spore IgG also inhibited the germination of spores
      in J774.1 macrophages, suggesting that opsonization of spores promotes
      phagocytosis and subsequent killing by macrophages. These results indicate the
      usefulness of spore surface antigens as vaccine targets. In combination with
      major virulence factors such as the PA, spore-associated antigens may offer a
      safer and more effective multicomponent vaccine for B. anthracis infection.

PMID- 17005990
TI  - The vesicle transport protein Vac1p is required for virulence of Candida
      albicans.
AB  - The putative vesicle transport protein Vac1p of the human pathogenic yeast
      Candida albicans plays an important role in virulence. To determine the cellular
      functions of Vac1p, a null mutant was generated by sequential disruption of both
      alleles. The vac1 null mutant strain showed defective endosomal vesicle
      transport, demonstrating a role of Vac1p in protein transport to the vacuole.
      Vac1p also contributes to resistance to metal ions, as the null mutant strain was
      hypersensitive to Cu(2+), Zn(2+) and Ni(2+). In addition, the loss of Vac1p
      affected several virulence factors of C. albicans. In particular, the vac1 null
      mutant strain showed defective hyphal growth, even when hyphal formation was
      induced via different pathways. Furthermore, Vac1p affects chlamydospore
      formation, adherence to human vaginal epithelial cells, and the secretion of
      aspartyl proteinases (Saps). Avirulence in a mouse model of systemic infection of
      the vac1 null mutant strongly suggests that Vac1p of C. albicans is essential for
      pathogenicity. In summary, the Vac1p protein is required for several cellular
      pathways, in particular those that control virulence and pathogenicity.
      Consequently, Vac1p is a novel and interesting target for antifungal drugs.

PMID- 17005991
TI  - The arl locus positively regulates Staphylococcus aureus type 5 capsule via an
      mgrA-dependent pathway.
AB  - Most clinical Staphylococcus aureus strains produce either type 5 or type 8
      capsular polysaccharides. The production of these capsules is influenced by
      various environmental factors. To study the regulation of capsule, Tn551
      transposon mutagenesis and transcriptional reporter gene fusion were employed to
      identify several putative regulatory loci that influenced capsule gene
      expression. One of these, the arl locus, was chosen for further analysis. Tn551
      was found to insert within the coding region (near the translational start site
      of the arlR gene). ArlR, along with ArlS, forms a two-component system that has
      been previously shown to affect autolysis and production of several secreted
      proteins. Phenotypic analyses of the arlR-specific mutant and gene fusion
      analyses showed that arlR activated capsule production at the transcriptional
      level. However, gel mobility shift assays did not support activation of the
      capsule genes by direct ArlR binding to the primary cap5 promoter region upstream
      of the operon. In contrast, it was found that arl activated mgrA, an activator
      for capsule production, whereas mgrA did not have a significant effect on arlR.
      Genetic studies supported the notion that arlR functions upstream of mgrA with
      respect to the regulation of capsule production, although gene fusion studies
      indicated that arl could also regulate capsule independently from mgrA.
      Collectively, the results suggest that arl positively regulates capsule
      production at the transcriptional level primarily through an mgrA-dependent
      pathway.

PMID- 17005992
TI  - Nutrient regulation of oligopeptide transport in Saccharomyces cerevisiae.
AB  - Small peptides (2-5 amino acid residues) are transported into Saccharomyces
      cerevisiae via two transport systems: PTR (Peptide TRansport) for di-/tripeptides
      and OPT (OligoPeptide Transport) for oligopeptides of 4-5 amino acids in length.
      Although regulation of the PTR system has been studied in some detail, neither
      the regulation of the OPT family nor the environmental conditions under which
      family members are normally expressed have been well studied in S. cerevisiae.
      Using a lacZ reporter gene construct fused to 1 kb DNA from upstream of the genes
      OPT1 and OPT2, which encode the two S. cerevisiae oligopeptide transporters, the
      relative expression levels of these genes were measured in a variety of
      environmental conditions. Uptake assays were also conducted to measure functional
      protein levels at the plasma membrane. It was found that OPT1 was up-regulated in
      sulfur-free medium, and that Ptr3p and Ssy1p, proteins involved in regulating the
      di-/tripeptide transporter encoding gene PTR2 via amino acid sensing, were
      required for OPT1 expression in a sulfur-free environment. In contrast, as
      measured by response to toxic tetrapeptide and by real-time PCR, OPT1 was not
      regulated through Cup9p, which is a repressor for PTR2 expression, although Cup9p
      did repress OPT2 expression. In addition, all of the 20 naturally occurring amino
      acids, except the sulfur-containing amino acids methionine and cysteine, up
      regulated OPT1, with the greatest change in expression observed when cells were
      grown in sulfur-free medium. These data demonstrate that regulation of the OPT
      system has both similarities and differences to regulation of the PTR system,
      allowing the yeast cell to adapt its utilization of small peptides to various
      environmental conditions.

PMID- 17005993
TI  - Glycerol, ethylene glycol and propanediol elicit pimaricin biosynthesis in the PI
      factor-defective strain Streptomyces natalensis npi287 and increase polyene
      production in several wild-type actinomycetes.
AB  - Production of pimaricin by Streptomyces natalensis ATCC 27448 is elicited by the
      PI-factor, an autoinducer secreted by the producer strain during the rapid growth
      phase. Exogenous PI-factor restored pimaricin production in a mutant strain
      npi287 defective in PI-factor biosynthesis. During purification of the PI-factor,
      a second pimaricin-inducing fraction different from PI-factor was isolated from
      the culture broth of wild-type S. natalensis ATCC 27448. After purification by
      HPLC and analysis by MS and NMR, this active fraction was shown to contain
      glycerol and lactic acid. Pure glycerol restored pimaricin production in liquid
      cultures of the autoinducer-defective npi287 mutant. A similar effect was exerted
      by ethylene glycol, 1,2-propanediol and 1,3-propanediol but not by higher
      polyalcohols or by glycerol acetate or glycerol lactate esters. Glycerol
      stimulated (30-270 %) the production of six different polyene macrolide
      antibiotics by their respective producer strains. Addition of glycerol to the
      inducer-defective npi287 strain restored pimaricin production but did not result
      in extracellular or intracellular accumulation of PI-factor. Exogenously added PI
      factor was internalized by the cells in the presence of glycerol, and a mixture
      of both PI-factor and glycerol produced a slightly higher inducing effect on
      pimaricin production than PI-factor alone. In summary, glycerol, ethylene glycol
      and propanediol exert a bypass of the PI-factor inducing effect on pimaricin
      biosynthesis.

PMID- 17005994
TI  - Identification and characterization of Pseudomonas membrane transporters
      necessary for utilization of the siderophore pyridine-2,6-bis(thiocarboxylic
      acid) (PDTC).
AB  - The compound pyridine-2,6-bis(thiocarboxylic acid) (PDTC) is known to be produced
      and excreted by three strains of Pseudomonas. Its reactivity includes the
      complete dechlorination of the environmental contaminant carbon tetrachloride.
      PDTC functions as a siderophore; however, roles as a ferric reductant and
      antimicrobial agent have also been proposed. PDTC function and regulation were
      further explored by characterizing the phenotypes of mutants in predicted
      membrane transporter genes. The functions of a predicted outer-membrane
      transporter (PdtK) and a predicted inner-membrane permease (PdtE) were examined
      in Pseudomonas putida DSM 3601. Uptake of iron from (55)Fe(III):PDTC, and
      bioutilization of PDTC in a chelated medium, were dependent upon PdtK and PdtE.
      Another strain of P. putida (KT2440), which lacks pdt orthologues, showed growth
      inhibition by PDTC that could be relieved by introducing a plasmid containing
      pdtKCPE. Transcriptional activation in response to exogenously added PDTC (25
      muM) was unaltered by the pdtK or pdtE mutations; each mutant showed activation
      of a pdt transcriptional reporter, indistinguishable from an isogenic PDTC
      utilization-proficient strain. The data demonstrate that PdtK and PdtE constitute
      a bipartite outer-membrane/inner-membrane transport system for iron acquisition
      from Fe(III):PDTC. Disruptions in this portion of the P. putida DSM 3601 pdt gene
      cluster do not abolish PDTC-dependent transcriptional signalling.

PMID- 17005995
TI  - Trans geometric isomers of EPA decrease LXRalpha-induced cellular triacylglycerol
      via suppression of SREBP-1c and PGC-1beta.
AB  - Dietary mono- or di-trans fatty acids with chain lengths of 18-22 increase the
      risk of cardiovascular diseases because they increase LDL cholesterol and
      decrease HDL cholesterol in the plasma. However, the effects of trans isomers of
      PUFAs on lipid metabolism remain unknown. Dietary PUFAs, especially
      eicosapentaenoic acid (EPA) in marine oils, improve serum lipid profiles by
      suppressing liver X receptor alpha (LXRalpha) activity in the liver. In this
      study, we compared the effects of trans geometric isomers of eicosapentaenoic
      acid (TEPA) on triacylglycerol synthesis induced by a synthetic LXRalpha agonist
      (T0901317) with the effects of EPA in HepG2 cells. TEPA significantly decreased
      the amount of cellular triacylglycerol and the expression of mRNAs encoding fatty
      acid synthase, stearoyl-CoA desaturase-1, and glycerol-3-phosphate
      acyltransferase induced by T0901317 compared with EPA. However, there was no
      significant difference between the suppressive effect of TEPA or EPA on the
      expression of sterol-regulatory element binding protein-1c (SREBP-1c) induced by
      T0901317. We found that TEPA, but not EPA, decreased the mRNA expression of
      peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta),
      which is a coactivator of both LXRalpha and SREBP-1. These results suggest that
      the hypolipidemic effect of TEPA can be attributed to a decrease not only in
      SREBP-1 but also in PGC-1beta expression.

PMID- 17005996
TI  - Cholestasis and hypercholesterolemia in SCD1-deficient mice fed a low-fat, high
      carbohydrate diet.
AB  - Stearoyl-coenzyme A desaturase 1-deficient (SCD1(-/-)) mice have impaired MUFA
      synthesis. When maintained on a very low-fat (VLF) diet, SCD1(-/-) mice developed
      severe hypercholesterolemia, characterized by an increase in apolipoprotein B
      (apoB)-containing lipoproteins and the appearance of lipoprotein X. The rate of
      LDL clearance was decreased in VLF SCD1(-/-) mice relative to VLF SCD1(+/+) mice,
      indicating that reduced apoB-containing lipoprotein clearance contributed to the
      hypercholesterolemia. Additionally, HDL-cholesterol was dramatically reduced in
      these mice. The presence of increased plasma bile acids, bilirubin, and
      aminotransferases in the VLF SCD1(-/-) mice is indicative of cholestasis.
      Supplementation of the VLF diet with MUFA- and PUFA-rich canola oil, but not
      saturated fat-rich hydrogenated coconut oil, prevented these plasma phenotypes.
      However, dietary oleate was not as effective as canola oil in reducing LDL
      cholesterol, signifying a role for dietary PUFA deficiency in the development of
      this phenotype. These results indicate that the lack of SCD1 results in an
      increased requirement for dietary unsaturated fat to compensate for impaired MUFA
      synthesis and to prevent hypercholesterolemia and hepatic dysfunction. Therefore,
      endogenous MUFA synthesis is essential during dietary unsaturated fat
      insufficiency and influences the dietary requirement of PUFA.

PMID- 17005997
TI  - The main triglyceride-lipase from the insect fat body is an active phospholipase
      A(1): identification and characterization.
AB  - The main triglyceride-lipase (TG-lipase) from the fat body of Manduca sexta has
      been identified as the homolog of Drosophila melanogaster CG8552. This protein is
      conserved among insects and also shares significant sequence similarity with
      vertebrate phospholipases (PLs) from the phosphatidic acid preferring
      phospholipase A1 (PA-PLA(1)) family. It is shown here that the TG-lipase is also
      a PL. TG-lipase and PL activities copurify and are inhibited by, or resistant to,
      the same lipase inhibitors, indicating that both activities are catalyzed by the
      same enzyme and active site. The PL activity of TG-lipase corresponded to PL type
      A(1). The concentration dependence of lipase activity with TG and PL micellar
      substrates showed saturation kinetics, with apparent K(m) values of 152 +/- 11
      and 7.8 +/- 1.1 muM, respectively. TG-lipase was able to hydrolyze the major
      phospholipid components of the lipid droplets, phosphatidylcholine and
      phosphatidylethanolamine. The enzyme hydrolyzes 77 molecules of TG for every
      molecule of PL contained in the lipid droplets. It was observed that the
      activation of lipolysis in vivo is accompanied by activation of the hydrolysis of
      phospholipids of the lipid droplets. These results suggest that the PL activity
      of the insect TG-lipase could be required to allow access of the lipase to TG
      molecules contained in the core of the lipid droplets.

PMID- 17005998
TI  - Returning to work with HIV/AIDS: a qualitative study.
AB  - In addition to being an outcome, workforce reentry is a process: People with
      HIV/AIDS attempting to go back to work must make initial decisions to engage in
      such an attempt, they then must go through a series of steps that may include re
      education or retraining, job searches, resume development, and other activities.
      Sustaining employment, in turn, entails its own set of activities. People
      attempting workforce reentry may also experience barriers on their journeys back
      to work, they may employ certain strengths to reach their goals, and they may use
      resources to facilitate preparation for work. Few studies have attempted to study
      this process. This study was designed to provide an initial attempt to study the
      process of workforce reentry. Abstracted information from the progress notes of
      104 people with HIV/AIDS attempting workforce reentry was qualitatively analyzed
      using a grounded theory approach to identify themes. Three major themes emerged
      with reliability: Barriers to workforce reentry, staff-identified strengths, and
      resources used in workforce-reentry efforts. Although none predicted successful
      workforce reentry, participants in the study experienced substantial barriers in
      their workforce-reentry efforts, staff identified significant strengths, and
      participants used appropriate resources in their efforts to go back to work.
      Implications for workforce-reentry programs for people with HIV/AIDS are
      discussed.

PMID- 17005999
TI  - Workforce reentry for people with HIV/AIDS: intervention effects and predictors
      of success.
AB  - Treatment that prolongs the lives of people with HIV/AIDS and improves their
      quality of life is relatively recent and little is known about factors that may
      predict their successful re-entry to the workforce. No data exist concerning the
      effectiveness of programs to assist people with HIV/AIDS in their efforts to
      return to work. We used logistic regression and Kaplan-Meier survival curves to
      predict return to work using data from 126 individuals who participated in an
      HIV/AIDS return to work program. Results from the 24 month follow-up revealed
      that program participation, general health, benefits status, and gender,
      predicted successful re-entry to the workforce. We discuss these findings in the
      context of the need for more explicitly-defined interventions, as well as the
      need for additional information on factors that may hinder or facilitate
      workforce re-entry among people with HIV/AIDS.

PMID- 17006000
TI  - Work status, benefits, and financial resources among people with HIV/AIDS.
AB  - With the advent of more advanced treatments and therapies, people with HIV/AIDS
      are experiencing significant improvements in their health, making many of their
      ongoing employment and career goals more realistic. However, people with HIV/AIDS
      continue to have major concerns regarding the impact of working on their benefits
      and entitlements, including apprehensions about potential economic hardships
      related to loss of financial supports and health insurance coverage. This article
      focuses on factors related to employment status, sources of health benefits, and
      entitlements among people with HIV/AIDS. In addition, results of the study
      demonstrate differences in employment status, benefit types, and the amount of
      financial support individuals receive based on gender.

PMID- 17006001
TI  - In-house work opportunities: implications for housing organizations serving
      persons living With HIV/AIDS.
AB  - Finding work and/or re-entering the workforce can be extremely challenging for
      persons living with HIV/AIDS. Also difficult is assisting them in the process,
      mostly because there is little documentation or resources about programs that
      provide vocational services specifically for this population. In response to this
      dilemma and because it was perceived as a win/win situation, three urban
      residential community organizations serving the HIV/AIDS population, decided
      independently to create in-house work opportunities for their clients. All of
      these organizations are a variation of the same theme: transitional/supportive
      housing for persons with HIV/AIDS that were formerly homeless and are now
      interested in becoming increasingly self-sufficient. This article will present a
      program description that addresses unique manner in which these three sites
      created in-house job programs in the areas of receptionist, kitchen, and
      maintenance work. More specifically, this paper will address the strengths,
      limitations, and ethical considerations that guided program development.

PMID- 17006002
TI  - Impairments and perceived competence in persons living with HIV/AIDS.
AB  - Medical advances have transformed HIV/AIDS from a short-term terminal illness to
      a long-term chronic condition. Consequently, the disability experience of persons
      with HIV illness has shifted from issues related to physical well-being to those
      concerning performance of daily life activities and wider community
      participation. These changes have necessitated rehabilitation interventions for
      persons with HIV/AIDS to focus on issues related to enabling participation in all
      spheres of everyday activities. However, limited information is available on the
      impairments prevalent in the emergent population of people living with HIV/AIDS
      and on the impact of these impairments on the person's functional performance and
      participation in various occupations of daily living. The present study attempted
      to explore these issues as they are experienced by the emergent population of
      people living with HIV/AIDS. The purpose of the study was: (1) to explore
      occupational functioning across various activities, (2) to describe the various
      impairments prevalent in this population, and (3) to examine the impact of these
      impairments on the person's perceived occupational competence. Two instruments,
      the Sign and symptom checklist for persons with HIV disease and the Occupational
      Self-Assessment were administered to a sample of 35 individuals (Mean age=42.8
      yrs.) living in supportive living facilities. Impairments most commonly
      identified by the participants included: fatigue; fear/worries; difficulty
      concentrating; muscle aches; and depression. The two primary areas of
      occupational functioning where participants reported experiencing moderate to
      severe difficulty included: managing finances and physically engaging in
      activities which were reported by 67.7% and 35.5% of the participants
      respectively. No statistically significant correlation was observed between
      various measures of impairments and the overall measure of perceived occupational
      competence for the sample of individuals living with HIV/AIDS included in this
      study.

PMID- 17006003
TI  - Occupational identity, occupational competence and occupational settings
      (environment): influences on return to work in men living with HIV/AIDS.
AB  - AIMS: The aim of this study was to examine and describe the relationship between
      the efforts of twelve men living with AIDS to reestablish a worker role following
      completion of a vocational rehabilitation program and changes in their
      occupational identity, occupational competence and perception of occupational
      settings (environment). METHODS: A series of in-depth interviews were conducted,
      transcribed and analyzed via categorical content analysis using sections of the
      text as the unit of analysis. FINDINGS: Findings illustrate how constructs
      measured by the sub-scales of the OPHI-II may be helpful in understanding how
      persons frame past, present and anticipated experiences as they attempt to
      reestablish a life role lost after the onset of disability. The findings are
      supported by the quantitative item hierarchies of the occupational identity,
      occupational competence and occupational settings (environment) scales
      established in earlier quantitative research via Rasch analysis. CONCLUSION: The
      constructs of occupational identity, occupational competence and occupational
      settings (environment) are useful constructs to aid in understanding the
      experiences and narratives of persons attempting to reenter a major life role.

PMID- 17006004
TI  - Living long-term with HIV/AIDS: exploring impact in psychosocial and vocational
      domains.
AB  - In the last decade, new treatments for the Human Immunodeficiency Virus (HIV) and
      Acquired Immune Deficiency Syndrome (AIDS) have led to improved health and longer
      life expectancies for many HIV-positive individuals. Coping with HIV/AIDS as a
      chronic, rather than terminal illness presents new challenges for those living
      with the disease and for service providers. This review of HIV/AIDS-related
      literature attempts to address the major medical, psychological and psychosocial
      challenges related to living long-term with HIV/AIDS and consider how they may
      present obstacles to attainment of educational and vocational goals for HIV
      positive individuals. Implications for service providers and suggestions for
      future research are discussed. An exploratory study of needs assessment is
      proposed.

PMID- 17006005
TI  - Interdisciplinary staff perceptions of an occupational therapy return to work
      program for people living with AIDS.
AB  - The purpose of this qualitative study was to identify the perception of
      interdisciplinary staff members regarding the impact of a model work and
      independent living oriented program for residents in supportive living
      facilities. This study used focus groups and individual interviews to collect
      these perceptions. Staff members identified four areas of impact: utilization of
      a holistic and process-oriented approach, an ability to identify and work with
      the strengths of clients, emphasis on the learning of practical skills, and
      creating an intersection for all aspects of services. These findings point to the
      fact that staff members found the value that occupational therapy has to offer
      their overall programming by improving participation of clients with HIV in
      learning practical skills for use in their daily lives and in developing work
      related skills.

PMID- 17006006
TI  - HIV/AIDS and return to work: a literature review one-decade post-introduction of
      combination therapy (HAART).
AB  - It has been a little over one decade since the introduction of the first protease
      inhibitor that ushered in new era of treatment for persons living with human
      immunodeficiency virus (HIV) and Acquired Immune-Deficiency Syndrome (AIDS). As
      of the end of 2003, an estimated 37.8 million people worldwide were infected with
      the HIV. It is estimated that there are 850,000-950,000 persons in the United
      States living with human immunodeficiency virus (HIV) and that the incident rate
      is new cases each year. Since AIDS affects so many people of working age in the
      US, issues of employment, work rehabilitation and AIDS in the workplace have all
      become major concerns. The paper presents a review of the literature published
      during a ten year period that is relevant to understanding the various needs and
      barriers related to work as well as services designed to address them.

PMID- 17006007
TI  - Return to work for individuals with Human Immunodeficiency Virus (HIV) disease:
      dichotomous outcome variable or personally-constructed narrative challenge?
AB  - Advances in the management of HIV disease have increasingly focused attention on
      the possibilities of return to employment for individuals with HIV disease.
      However whilst mortality has decreased and life expectancies have lengthened,
      life for the individual with HIV remains both complex and unpredictable. This
      article explores the notion of return to work as narrative theme. A case study
      highlighting the narrative nature of how return to work might be conceptualised
      by the HIV positive individual is presented; ahead of a brief discussion as to
      how the lived reality of combination therapy may impact upon the individual's
      conceptualisation of employment in the broader context of their life story.

PMID- 17006008
TI  - Psychometric properties of the Worker Role Interview.
AB  - OBJECTIVES: This study examined the psychometric properties of the rating scale
      of the Worker Role Interview (WRI). The study also asked whether the scale's
      items formed a valid measure of the construct, psychosocial capacity for work,
      and whether they were targeted to and could effectively discriminate between
      persons at different levels of psychosocial ability for work. METHOD OF STUDY:
      Data were collected from 21 raters on 440 participants from the United States,
      Sweden and Iceland. A many-faceted Rasch model was used to analyze the data.
      RESULTS: Most items of the scale worked effectively to measure the underlying
      construct for which the WRI was designed. In addition, the items were ordered
      from least to more of the underlying construct as expected. The scale validly
      measured 90.23% of the participants, who varied by nationality, culture, age and
      diagnostic status. The scale's items distinguished participants into
      approximately three different strata and were appropriately targeted to the
      participants. Seventeen of the 21 raters used scale in a valid manner.
      CONCLUSIONS: The WRI scale and items are valid across ages, diagnoses, and
      culture and effectively measure a wide range of persons.

PMID- 17006009
TI  - Worker role identity development of women with disabilities who experience
      domestic violence.
AB  - This two-year longitudinal qualitative study explored worker role identity
      development of seven women with disabilities who experienced domestic violence.
      Yearly semi-structured interviews and monthly follow up calls elucidated the
      meaning of work in women's lives and the development of role identity during
      transitions from shelters to the community. Participants aged 26-47, were from
      two domestic violence shelters and an independent living center in the Midwestern
      United States. Data analyses, using constant comparative methods, a peer team and
      member checking, revealed that women's work roles remained in a state of identity
      diffusion. Identity diffusion in the worker role was delineated into three
      themes: role ambivalence, impact of disability, and relationship of the worker
      role to other roles. Study findings suggest a conflict between staff urgency to
      support women's return to work and economic self-sufficiency, and women's
      readiness to assume stronger work identities.

PMID- 17006010
TI  - Microbiology of the insect gut:tales from mosquitoes and bees.

PMID- 17006011
TI  - Membrane interfacial localization of aromatic amino acids and membrane protein
      function.

PMID- 17006012
TI  - The mobility principle: how I became a molecular biologist.

PMID- 17006013
TI  - Living in a physical world VIII. Gravity and life in water.

PMID- 17006014
TI  - What history tells us VI. The transfer of behaviours by macromolecules.

PMID- 17006015
TI  - Characterization of the Helicoverpa assulta nucleopolyhedrovirus genome and
      sequence analysis of the polyhedrin gene region.
AB  - A local strain of Helicoverpa assulta nucleopolyhedrovirus (HasNPV) was isolated
      from infected H.assulta larvae in Korea. Restriction endonuclease fragment
      analysis, using 4 restriction enzymes, estimated that the total genome size of
      HasNPV is about 138 kb. A degenerate polymerase chain reaction (PCR) primer set
      for the polyhedrin gene successfully amplified the partial polyhedrin gene of
      HasNPV. The sequencing results showed that the about 430 bp PCR product was a
      fragment of the corresponding polyhedrin gene. Using HasNPV partial predicted
      polyhedrin to probe the Southern blots, we identified the location of the
      polyhedrin gene within the 6 kb Eco RI, 15 kb Nco I, 20 kb Xho I, 17 kb Bgl II
      and 3 kb Cla I fragments, respectively. The 3 kb Cla I fragment was cloned and
      the nucleotide sequences of the polyhedrin coding region and its flaking regions
      were determined. Nucleotide sequence analysis indicated the presence of an open
      reading frame of 735 nucleotides which could encode 245 amino acids with a
      predicted molecular mass of 29 kDa. The nucleotide sequences within the coding
      region of HasNPV polyhedrin shared 73.7% identity with the polyhedrin gene from
      Autographa californica NPV but were most closely related to Helicoverpa and
      Heliothis species NPVs with over 99% sequence identity.

PMID- 17006016
TI  - Agrobacterium-mediated transformation of chickpea with alpha-amylase inhibitor
      gene for insect resistance.
AB  - Chickpea is the world's third most important pulse crop and India produces 75% of
      the world's supply. Chickpea seeds are attacked by Callosobruchus maculatus and
      C. chinensis which cause extensive damage. The alpha-amylase inhibitor gene
      isolated from Phaseolus vulgaris seeds was introduced into chickpea cultivar K850
      through Agrobacterium-mediated transformation. A total of 288 kanamycin resistant
      plants were regenerated. Only 0.3% of these were true transformants. Polymerase
      chain reaction (PCR) analysis and Southern hybridization confirmed the presence
      of 4.9 kb alpha-amylase inhibitor gene in the transformed plants. Western blot
      confirmed the presence of alpha-amylase inhibitor protein. The results of
      bioassay study revealed a significant reduction in the survival rate of bruchid
      weevil C. maculatus reared on transgenic chickpea seeds. All the transgenic
      plants exhibited a segregation ratio of 3:1.

PMID- 17006017
TI  - Modulation of glucose uptake in adipose tissue by nitric oxide-generating
      compounds.
AB  - There is increasing evidence that endogenous nitric oxide (NO) influences
      adipogenesis, lipolysis and insulin-stimulated glucose uptake. We investigated
      the effect of NO released from S-nitrosoglutathione (GSNO) and S-nitroso-N
      acetylpenicillamine (SNAP) on basal and insulin-stimulated glucose uptake in
      adipocytes of normoglycaemic and streptozotocin (STZ)-induced diabetic rats. GSNO
      and SNAP at 0.2,0.5, and 1 mM brought about a concentration-dependent increase in
      basal and insulin-stimulated 2-deoxyglucose uptake in adipocytes of
      normoglycaemic and STZ-induced diabetic rats. SNAP at 1.0 mM significantly
      elevated basal 2-deoxyglucose uptake (115.8+/-10.4% compared with GSNO at the
      same concentration (116.1+/-9.4%; P less than 0.05) in STZ-induced diabetic rats.
      Conversely, SNAP at concentrations of 10 mM and 20 mM significantly decreased
      basal 2-deoxyglucose uptake by 50.0+/-4.5% and 61.5+/-7.2% respectively in
      adipocytes of STZ-induced diabetic rats (P less than 0.05). GSNO at
      concentrations of 10 mM and 20 mM also significantly decreased basal 2
      deoxyglucose uptake by 50.8+/-6.4% and 55.2+/-7.8% respectively in adipocytes of
      STZ-induced diabetic rats (P less than 0.05). These observations indicate that NO
      released from GSNO and SNAP at 1 mM or less stimulates basal and insulin
      stimulated glucose uptake,and at concentrations of 10 mM and 20 mM inhibits basal
      glucose uptake. The additive effect of GSNO or SNAP, and insulin observed in this
      study could be due to different mechanisms and warrants further investigation.

PMID- 17006019
TI  - Aujeszky's disease virus production in disposable bioreactor.
AB  - A novel, disposable-bag bioreactor system that uses wave action for mixing and
      transferring oxygen was evaluated for BHK 21 C13 cell line growth and Aujeszky's
      disease virus (ADV) production. Growth kinetics of BHK 21 C13 cells in the wave
      bioreactor during 3-day period were determined. At the end of the 3-day culture
      period and cell density of 1.82x10(6) cells ml-1, the reactor was inoculated with
      9 ml of gE- Bartha K-61 strain ADV suspension (10(5.9) TCID50) with multiplicity
      of infection (MOI) of 0.01. After a 144 h incubation period, 400 ml of ADV
      harvest was obtained with titre of 10(7.0) TCID 50 ml-1, which corresponds to
      40,000 doses of vaccine against AD. In conclusion, the results obtained with the
      wave bioreactor using BHK 21 C13 cells showed that this system can be considered
      as suitable for ADV or BHK 21 C13 cell biomass production.

PMID- 17006018
TI  - The effect of some osmolytes on the activity and stability of mushroom
      tyrosinase.
AB  - The thermodynamical stability and remained activity of mushroom tyrosinase (MT)
      from Agaricus bisporus in 10 mM phosphate buffer, pH 6.8, stored at two
      temperatures of 4 and 40 degrees C were investigated in the presence of three
      different amino acids (His, Phe and Asp) and also trehalose as osmolytes, for
      comparing with the results obtained in the absence of any additive. Kinetics of
      inactivation obey the first order law. Inactivation rate constant (kinact) value
      is the best parameter describing effect of osmolytes on kinetic stability of the
      enzyme. Trehalose and His have the smallest value of kinact (0.7x10(-4) s-1) in
      comparison with their absence (2.5x10(-4) s-1). Moreover, to obtain effect of
      these four osmolytes on thermodynamical stability of the enzyme, protein
      denaturation by dodecyl trimethylammonium bromide (DTAB) and thermal scanning was
      investigated. Sigmoidal denaturation curves were analysed according to the two
      states model of Pace theory to find the Gibbs free energy change of denaturation
      process in aqueous solution at room temperature, as a very good thermodynamic
      criterion indicating stability of the protein. Although His, Phe and Asp induced
      constriction of MT tertiary structure, its secondary structure had not any change
      and the result was a chemical and thermal stabilization of MT. The enzyme shows a
      proper coincidence of thermodynamic and structural changes with the presence of
      trehalose. Thus, among the four osmolytes, trehalose is an exceptional protein
      stabilizer.

PMID- 17006020
TI  - Dominance hierarchy and social grooming in female lion-tailed macaques (Macaca
      silenus) in the Western Ghats, India.
AB  - This article reports the structure of dominance and its relationship with social
      grooming in wild lion-tailed macaque females. The strength of dominance hierarchy
      was 0.79 on a scale of 0 to 1 indicating a moderate linearity in the ranking
      system. Dominance scores were converted into an ordinal as well as an interval
      scale. Grooming scores were also converted into interval scales using standard
      scores. Grooming received and grooming given correlated positively and negatively
      respectively with dominance ranks indicating that high ranking females received
      more and gave less grooming. Grooming was also positively related to encounter
      rates for dyads of females. More grooming among adjacent ranks, and grooming
      being more reciprocal, occurred only in the case of dominant females. The
      grooming patterns, therefore, appeared to be more of despotic than egalitarian
      nature. While ranking macaques into different Grades of social systems ranging
      from despotic to egalitarian, Thierry (2004) has placed lion-tailed macaques in
      Grade 3 corresponding to the 'relaxed' social system. Our results indicate that
      the grooming and dominance relationships in this species are more despotic, and
      hence, the Grade for this species requires to be shifted toward 2 or 1.

PMID- 17006021
TI  - The sperm of Hylodinae species (Anura, Leptodactylidae): ultrastructural
      characteristics and their relevance to interspecific taxonomic relationships.
AB  - Hylodinae leptodactylids (sensu Lynch 1971) form a group of diurnal frogs, which
      is hypothesized on the basis of morphological traits to be the closest relatives
      of the dendrobatid frogs. Our study describes ultrastructural characteristics of
      sperm from three hylodine species (Hylodes phyllodes, Crossodactylus sp. n. and
      Megaelosia massarti) to reassess the intergeneric relationships within the
      Hylodinae, as well as the supposed relationship between the Hylodinae and
      Dendrobatidae. The ultrastructure of the sperm is very similar among the three
      species and is indicative of its conserved nature within the Hylodinae. The
      structure of the acrosomal complex was very similar to that of other
      leptodactylid species, to most of the remaining species included in the
      Bufonoidea lineage, and also to that observed in the dendrobatid species examined
      so far. Since such a structure has been considered a plesiomorphic trait, it
      contributes little to our understanding of the relationships between the
      Hylodinae and Dendrobatidae. The flagellar apparatus of Crossodactylus sp. n. is
      very similar to that of most leptodactylids. The sperm of Megaelosia massarti and
      Hylodes phyllodes display a distinctive condition in their axial and juxtaxonemal
      fibers. This distinctive flagellar condition expands the already known
      variability in sperm structure within the Leptodactylidae.

PMID- 17006022
TI  - The reactive oxygen species network pathways:an essential prerequisite for
      perception of pathogen attack and the acquired disease resistance in plants.
AB  - Availability of complete Arabidopsis (Arabidopsis thaliana) and rice (Oryza
      sativa) genome sequences, together with molecular recourses of functional
      genomics and proteomics have revolutionized our understanding of reactive oxygen
      species (ROS) signalling network mediating disease resistance in plants. So far,
      ROS have been associated with aging, cellular and molecular alteration in animal
      and plant cells. Recently,concluding evidences suggest that ROS network is
      essential to induce disease resistance and even to mediate resistance to multiple
      stresses in plants. ROS are obligatory by-products emerging as a result of normal
      metabolic reactions. They have the potential to be both beneficial and harmful to
      cellular metabolism. Their dual effects on metabolic reactions are dosage
      specific. In this review we focus our attention on cellular ROS level to trigger
      beneficial effects on plant cells responding to pathogen attack. By exploring the
      research related contributions coupled with data of targeted gene disruption, and
      RNA interference approaches, we show here that ROS are ubiquitous molecules of
      redox-pathways that play a crucial role in plant defence mechanism. The molecular
      prerequisites of ROS network to activate plant defence system in response to
      pathogen infections are here underlined. Bioinformatic tools are now available to
      scientists for high throughput analysis of cellular metabolisms. These tools are
      used to illustrate crucial ROS-related genes that are involved in the defence
      mechanism of plants. The review describes also the emerging findings of ROS
      network pathways to modulate multiple stress resistance in plants.

PMID- 17006023
TI  - Laminopathies: multiple disorders arising from defects in nuclear architecture.
AB  - Lamins are the major structural proteins of the nucleus in an animal cell. In
      addition to being essential for nuclear integrity and assembly, lamins are
      involved in the organization of nuclear processes such as DNA replication,
      transcription and repair. Mutations in the human lamin A gene lead to highly
      debilitating genetic disorders that primarily affect muscle, adipose, bone or
      neuronal tissues and also cause premature ageing syndromes. Mutant lamins alter
      nuclear integrity and hinder signalling pathways involved in muscle
      differentiation and adipocyte differentiation, suggesting tissue-specific roles
      for lamins. Furthermore, cells expressing mutant lamins are impaired in their
      response to DNA damaging agents. Recent reports indicate that certain lamin
      mutations act in a dominant negative manner to cause nuclear defects and cellular
      toxicity, and suggest a possible role for aberrant lamins in normal ageing
      processes.

PMID- 17006025
TI  - Epidemiology of depression among infertile and fertile couples in Shiraz,
      southern Iran.
AB  - BACKGROUND: Depression is considered as one of the main psychological disorders
      associated with infertility. Depression may play a significant role in the life
      of infertile individuals, their infertility treatment follow-up and in their
      hopefulness for the future; it may also influence the intensity and
      continuousness of the mutual relationship of the affected couple. AIMS: This
      study was done to determine the depression rate and make a comparison between
      infertile and fertile couples with respect to the same. SETTING AND DESIGN: The
      depression rate was evaluated between two groups--infertile couples (case group)
      and fertile couples (control group). MATERIALS AND METHODS: Ninety-one infertile
      couples (cases) and 9l fertile ones (controls) were randomly enrolled in our
      study. Beck depression inventory (BDI) and demographic information were provided.
      STATISTICAL ANALYSIS: We used Chi-square, t-test; and one-way Analysis of
      Variance (ANOVA) was performed to find out significant difference between
      infertility duration in various couples and its effect on the score of
      depression. RESULTS: The BDI mean difference between infertile and fertile
      couples was significant (P=0.015). It was significantly more among couples with
      infertility from 1-3 years' duration compared to those with infertility of 1-year
      duration or less. CONCLUSION: Regarding the high rate of depression among
      infertile couples, it seems necessary to pay more attention to infertility
      centers that offer psychological and psychiatric services.

PMID- 17006024
TI  - Cyclic AMP response element binding protein and brain-derived neurotrophic
      factor: molecules that modulate our mood?
AB  - Depression is the major psychiatric ailment of our times, afflicting
      approximately 20% of the population. Despite its prevalence, the pathophysiology
      of this complex disorder is not well understood. In addition, although
      antidepressants have been in existence for the past several decades, the
      mechanisms that underlie their therapeutic effects remain elusive. Building
      evidence implicates a role for the plasticity of specific neuro-circuitry in both
      the pathophysiology and treatment of depression. Damage to limbic regions is
      thought to contribute to the etiology of depression and antidepressants have been
      reported to reverse such damage and promote adaptive plasticity. The molecular
      pathways that contribute to the damage associated with depression and
      antidepressant-mediated plasticity are a major focus of scientific enquiry. The
      transcription factor cyclic AMP response element binding protein (CREB) and the
      neurotrophin brain-derived neurotrophic factor (BDNF) are targets of diverse
      classes of antidepressants and are known to be regulated in animal models and in
      patients suffering from depression. Given their role in neuronal plasticity, CREB
      and BDNF have emerged as molecules that may play an important role in modulating
      mood. The purpose of this review is to discuss the role of CREB and BDNF in
      depression and as targets/mediators of antidepressant action.

PMID- 17006026
TI  - Study on the injection practices of health facilities in Jingzhou district,
      Hubei, China.
AB  - BACKGROUND: Some studies indicate unsafe injection practices, which are
      associated with the transmission of blood-borne pathogens, exist extensively, in
      the developing countries. AIMS: To investigate the status of injection services,
      knowledge and attitude of health workers with regard to injection practices at
      all levels of the health facilities in Jingzhou district of China; and to provide
      useful scientific data in order to formulate a feasible, standard measure on
      injection safety. SETTINGS: Four district health care facilities, 6 township
      health centers, 14 village clinics and 14 community health stations. DESIGN: A
      retrospective cross-sectional study. MATERIALS AND METHODS: By examining the
      medical records in 2004, observing injection practices and interviewing health
      workers, the quantitative and qualitative data were collected and analyzed.
      RESULTS: Out of 1,452 medical records sampled, 1,450 patients had received at
      least one injection in the period of hospitalization, with an injection rate of
      about 100% and an average of 10.9 injections per patient. The most frequent
      injected drug was antibiotic (48%, 7,674/15,857). The prescriptions of 5,655
      outpatients were detected, with an injection rate of 52% (2,962). The field
      observation found that the proportion of unsafe injections was 16% (28/175) and
      that of unnecessary injections was 57% (99/175). Among 118 professional employees
      interviewed, those who knew that human immunodeficiency virus, hepatitis C virus
      and hepatitis B virus might be transmitted by the contaminated syringes and
      needles accounted for 95% (112), 59% (70) and 89% (105) respectively.
      CONCLUSIONS: Among the medical facilities of Jingzhou district, the injection
      rate was very high and the quality of injection practices should be further
      improved.

PMID- 17006027
TI  - Angiotensin converting enzyme inhibitors and aortic arch obstructive
      malformations.
AB  - We describe two newborn infants with aortic arch obstructive malformations who
      became anuric after initiation of captopril. Since angiotensin converting enzyme
      inhibitors can alter renal blood flow by reduction in angiotensin II and blocking
      autoregulation phenomenon, it is important to use them with great caution in
      neonates with aortic arch obstructive malformations, while monitoring their renal
      function closely.

PMID- 17006029
TI  - The diagnosis of intravenous leiomyomatosis of an early stage is difficult.

PMID- 17006028
TI  - Syphilitic myeloradiculopathy and pupillary light near disassociation: an overlap
      syndrome in a HIV positive individual.

PMID- 17006030
TI  - Hypothyroidism caused by thalidomide.

PMID- 17006031
TI  - Development of safer molecules through chirality.
AB  - Many of the drugs currently used in medical practice are mixtures of enantiomers
      (racemates). Many a times, the two enantiomers differ in their pharmacokinetic
      and pharmacodynamic properties. Replacing existing racemates with single isomers
      has resulted in improved safety and/or efficacy profile of various racemates. In
      this review, pharmacokinetic and pharmacodynamic implications of chirality are
      discussed in brief, followed by an overview of some important chiral switches
      that have yielded safer alternatives. These include levosalbutamol, S-ketamine,
      levobupivacaine, S-zopiclone, levocetirizine, S-amlodipine, S-atenolol, S
      metoprolol, S-omeprazole, S-pantoprazole and R-ondansetron. Few potential chiral
      switches under evaluation and some chiral switches that have not been successful
      are also discussed.

PMID- 17006032
TI  - Infant and child feeding index.
AB  - Traditional indicators of child feeding practices are widely used and appear to
      be useful, although the validity and reliability of those related to
      complementary feeding have not been established. Composite child feeding indices
      have the potential to address some of the methodological constraints related to
      the quantitative measurement of child feeding practices. They can address the
      multi-dimensionality of child feeding practices i.e. the need to consider the
      type, quality, texture, nutrient density of food, frequency of feeding and
      diversity of the diet; the age-specificity of child feeding practices; and the
      fact that feeding practices tend to cluster. The main advantage of creating a
      composite index is that it allows construction of one variable representing
      various dimensions of feeding or care practices. This variable, in turn, can be
      used to illustrate graphically the importance of child feeding or care for child
      outcomes or to model their determinants. This can be invaluable for advocacy,
      apart from being an indispensable tool for the purposes of research, monitoring
      and evaluation. Experience with creation of composite child feeding indices with
      the studies in Accra and DHS data sets from Latin America and Ethiopia has been
      encouraging and suggests that this is a promising area for future development and
      program applications.

PMID- 17006033
TI  - Which clinical signs and symptoms predict hypoxemia in acute childhood asthma?
AB  - OBJECTIVE: To find the clinical signs that are the best predictors of hypoxemia
      (SpO2 =92%) in acute asthma in children. METHODS: Color of skin, dyspnea (by
      single breath counting), alertness, respiratory rate, presence of audible wheeze,
      wheezing on auscultation, accessory muscle use, nasal flaring, pulse rate,
      systolic and diastolic blood pressure, pulsus paradoxus and oxygen saturation at
      room air (by pulse oximetry) were recorded at the time of presentation and one
      hour after presentation after completion of 3 doses of nebulized salbutamol and
      budesonide. RESULTS: Hypoxemia (SpO2 92% pounds sterling) was seen in 45%
      children at presentation and 14(28.6%) after one hour. The clinical signs that
      correlated significantly with hypoxemia at both time points were dyspnea assessed
      by single breath count (OR 3.3, 95% CI 0.9-12.9), accessory muscle use score > or
      = 3 (OR 3.0, 95% CI 0.9-15.4) and pulsus paradoxus> 10 (OR 3.0, 95% CI 0.7-13.6).
      In a multiple logistic regression model accessory muscle score > or = 3 and
      pulsus paradoxus> 10 were identified as independent predictors of hypoxemia
      (sensitivity 64.3%, specificity 91%). CONCLUSION: Physical assessment in a child
      with acute exacerbation of asthma should at least include accessory muscle use
      and pulsus paradoxus, since these predict hypoxemia the best.

PMID- 17006034
TI  - Hypoxemia in children with pneumonia and its clinical predictors.
AB  - OBJECTIVES: To assess the prevalence of hypoxemia in children, 2 months to 5
      years of age, with pneumonia and to identify its clinical predictors. METHODS:
      Children between 2-60 months of age presenting with a complaint of cough or
      difficulty breathing were assessed. Hypoxemia was defined as an arterial oxygen
      saturation of < 90% recorded by a portable pulse oximeter. Patients were
      categorized into groups: cough and cold, pneumonia, severe pneumonia and very
      severe pneumonia. RESULTS: The prevalence of hypoxemia (SpO2 of < 90%) in 150
      children with pneumonia was 38.7%. Of them 100% of very severe pneumonia, 80% of
      severe and 17% of pneumonia patients were hypoxic. Number of infants with
      respiratory illness (p value = 0.03) and hypoxemia (Odds ratio = 2.21, 95% CI
      1.03, 4.76) was significantly higher. Clinical predictors significantly
      associated with hypoxemia on univariate analysis were lethargy, grunting, nasal
      flaring, cyanosis, and complaint of inability to breastfeed/drink. Chest
      indrawing with 68.9% sensitivity and 82.6% specificity was the best predictor of
      hypoxemia. CONCLUSION: The prevalence and clinical predictors of hypoxemia
      identified validate the WHO classification of pneumonia based on severity. Age <
      1 year in children with ARI is an important risk factor for hypoxemia.

PMID- 17006035
TI  - Suicidal behaviors in adolescents.
AB  - OBJECTIVE: Suicidal ideation and suicide attempt are generally considered as non
      fatal suicidal behaviors (NFSB) by most researchers. Across different cultures,
      the prevalence of NFSB has been found to be alarmingly high among adolescents. As
      there is no published study estimating prevalence rates in India, we conducted a
      study on adolescents in Delhi to find prevalence of NFSB and other related
      behaviors and to identify risk factors for NFSB. METHODS: We collected data from
      1205 adolescents in the age group from 12 to 19 years from 2 schools through semi
      structured questionnaire on demographic variables, NFSB, death wish, deliberate
      self harm (DSH), Adjustment Inventory for School Students (AISS) by Sinha et al.
      &BDI. RESULTS: Prevalence of suicidal ideation (lifetime), suicidal ideation
      (last year), suicide attempt (lifetime), suicide attempt (last year) were 21.7%,
      11.7%, 8% and 3.5%, respectively. All the significant variables were entered into
      a logistic regression analysis model and the adjusted odds ratios, with 95%
      confidence intervals, were obtained for them. Hindu religion, female sex, older
      adolescent, physical abuse by parents, feeling neglected by parents, history of
      running away from school, history of suicide by a friend, death wish and DSH were
      found to be significant risk factors for NFSB. CONCLUSIONS: There is high
      prevalence of suicidal ideation, suicide attempt, death wish and deliberate self-
      harm in adolescent population of two schools in Delhi. Clinical implications of
      these findings are discussed.

PMID- 17006036
TI  - Educational provisions and learning disability.
AB  - OBJECTIVE: To assess the impact of the provisions of the Maharashtra government
      on the academic performance of children with specific learning disability (SpLD)
      at the Secondary School Certificate (SSC) board examination. METHODS: The
      academic performance of 60 children (45 boys, 15 girls) at the SSC board
      examination with benefit of chosen provisions was compared with their performance
      at their last annual school examination before diagnosis of SpLD. RESULTS: There
      was a significant improvement in their mean percentage (%) total marks scored at
      the SSC board examination as compared with the mean % total marks scored by them
      at their last annual school examination before the diagnosis (63.48 +/- 7.86 vs.
      40.95 +/- 7.23) [mean +/- SD, mean % difference = 22.53, 95% CI = 19.8 - 25.26,
      P. CONCLUSION: Children with SpLD who availed the benefit of provisions showed a
      significant improvement in their academic performance at the SSC board
      examination.

PMID- 17006037
TI  - Iodine nutritional status of children in North East India.
AB  - OBJECTIVE: To assess the iodine nutritional status of school children in selected
      areas of Imphal West District of Manipur where endemic goitre and associated
      iodine deficiency disorders (IDD) are prevalent in the post-salt iodization
      period. METHODS: A total of 961 school children in the age group 6-12 yrs of both
      sexes were clinically examined for goiter from three study areas- one from rural
      block and two from urban areas. One hundred twenty urine samples were analysed
      for iodine and thiocyanate respectively. One hundred and five edible salt samples
      were also collected from the households to evaluate the iodine content. Drinking
      water samples from different sources were collected and iodine level was analysed
      to study the bioavailability of iodine in the region. RESULTS: The total goiter
      rate was 34.96% (Grade 1- 32.15%; Grade 2- 2.81%) showing that IDD is a severe
      public health problem. The median urinary iodine levels in the studied areas were
      in the ranges from 12.5-17.5 microg/dl indicating no biochemical iodine
      deficiency in the region. Mean urinary thiocyanate level was 0.839+/-0.33 mg/dl
      showing that the people consume sufficient foods containing thiocyanate
      precursors. About 82% salt samples had iodine level more than 30 ppm and the
      iodine content in salt samples less than 15 ppm was only about 3% indicating the
      salt samples at house hold contain adequate iodine. CONCLUSION: Iodine content in
      drinking water samples ranged from 1.8-2.6 microg/l showing that the studied
      region is environmentally iodine deficient. Inspite of the consumption of
      adequate iodine, the existing goiter prevalence among school children during post
      salt iodization phase ensures that environmental factors other than iodine
      deficiency may have the possible role in the persistence of endemic goiter in the
      population. The role of thiocyanate in this regard may not be ruled out.

PMID- 17006038
TI  - Tracking progress towards sustainable elimination of iodine deficiency disorders
      in Bihar.
AB  - OBJECTIVES: To assess the status of the iodine deficiency in the population of
      Bihar and track progress of the elimination efforts. METHODS: A community based
      field survey was conducted. Using quantitative and qualitative research methods,
      data was collected by following internationally recommended protocol and
      methodology. Thirty clusters were selected using population proportionate to size
      technique. School age children (6 to 12 years) were the target group studied.
      Urinary iodine in target children and iodine content of salt at households were
      the indicators used. RESULTS: Total of 1169 children were studied. The median
      urinary iodine concentration was found to be 85.6 microg/L. Urinary iodine
      concentration was less than 50 microg/L in 31.5% of the subjects. Only 40.1% of
      the household salt samples were found to be adequately iodised as determined by
      titration method (> or =15 ppm iodine). CONCLUSIONS: Study results show existence
      of iodine deficiency in the state. There is need to accelerate our efforts to
      achieve iodine sufficiency and this should be done on a war-footing.

PMID- 17006039
TI  - Hepatitis B virus mutation in children.
AB  - Due to the lack of proof reading activity of hepatitis B virus (HBV) polymerase,
      mutation/variation of the viral sequence is frequently found during long term
      follow-ups. In the majority of children with chronic HBV infection, wild type HBV
      is the dominant viral strain during the natural course of chronic HBV infection.
      During long-term follow-up, HBV precore mutants developed spontaneously in
      approximately 10 to 24% of children before HBeAg seroconversion and in around 50%
      of children after HBeAg seroconversion mutants. Occasionally, children may be
      infected primarily by mutant strains of HBV. Approximately 36% of children with
      fulminant hepatitis and 30% of children with acute hepatitis B were infected by
      precore mutants of HBV transmitted by their mothers or blood donors. In addition,
      after universal HBV vaccination, HBV surface gene variants emerge or are selected
      under the immune pressure generated by the host or by administration of hepatitis
      B immune globulin and hepatitis B vaccination. In HBV DNA positive children from
      four sequential surveys in Taiwan, the prevalence of hepatitis B surface gene a
      determinant mutants increased from 7.8% before the vaccination program, to 19.6%,
      28.1% and 23.1% at 5, 10 and 15 years after the program. Nucleoside analogue may
      also induce mutant strains, which reduces the antiviral effects. The most common
      example is the YMDD mutation of the HBV polymerase gene after antiviral therapy
      with lamivudine. It developed in 19% of the treated children. In conclusion,
      children may be infected primarily by mutant strains of HBV either naturally
      during acute HBV infection. Those infected with wild type HBV initially may
      develop mutant strains gradually during the course of chronic infection under the
      host immune pressure. Vaccine escape mutants may develop after immunoprophylaxis.
      In addition, antiviral therapy with nucleoside analogues may also induce drug
      resistant mutant strains. Understanding the viral mutation status will help to
      design accurate strategies of immmunoprophylaxis and antiviral therapy against
      HBV infection.

PMID- 17006040
TI  - Liver involvement in celiac disease.
AB  - Celiac disease may present as a cryptogenic liver disorder being found in 5-10 %
      of patients with a persistent and cryptogenetic elevation of serum
      aminotransferase activity. In fact, a wide spectrum of liver injuries in children
      and adults may be related to CD and in particular: (1) a mild parenchymal damage
      characterised by absence of any clinical sign or symptom suggesting a chronic
      liver disease and by non-specific histological changes reversible on a gluten
      free diet; (2) a chronic inflammatory liver injury of autoimmune mechanism,
      including autoimmune hepatitis, primary sclerosing cholangitis and primary
      biliary cirrhosis, that may lead to fibrosis and cirrhosis, generally unaffected
      by gluten withdrawal and necessitating an immunosuppressive treatment; (3) a
      severe liver failure potentially treatable by a gluten-free diet. Such different
      types of liver injuries may represent a spectrum of a same disorder where
      individual factors, such as genetic predisposition, precocity and duration of
      exposure to gluten may influence the reversibility of liver damage. A rigorous
      cross-checking for a asymptomatic liver damage in CD individuals and conversely,
      for CD in any cryptogenic liver disorder including end-stage liver failure is
      recommended.

PMID- 17006041
TI  - Liver abscess in children.
AB  - Liver abscesses are frequently observed in pediatric clinical practice in tropics
      and subtropics especially in developing countries. Children have unique set of
      predisposing factors which have been highlighted. Expected microbiology and
      setting for unusual organisms are mentioned. Clinical presentations', including
      importance of location and number of abscesses has been discussed. Role of each
      modality of treatment clarified. Importance and limitations of investigations and
      imaging explained and complications and mortality discussed.

PMID- 17006042
TI  - Ascites in childhood liver disease.
AB  - Ascites is a common clinical problem in children with liver disease. The
      peripheral arterial vasodilation hypothesis is mostly accepted as the
      pathophysiological basis of ascites. The most important complication is
      spontaneous ascitic fluid infection in the form of spontaneous bacterial
      peritonitis (SBP) and its variants. Aerobic gram-negative bacteria, primarily
      Escherichia coli, are the most common isolates. Diagnostic paracentesis is done
      in patients with ascites when diagnosed first time and at the beginning of each
      admission to hospital. Ascitic fluid is evaluated for cell count with
      differential, albumin level, total protein and culture. Serum-ascites albumin
      gradient (SAAG) is the best single test for classifying ascites into portal
      hypertensive (SAAG> 1.1 g/dL) and non-portal hypertensive (SAAG < 1.1 g/dL)
      causes. In patients with tense ascites LVP should be performed. A neutrophil
      count of > 250 cells/mm3 is highly suggestive of bacterial peritonitis.
      Intravenous cefotaxime is the empiric antibiotic of choice. Long-term
      administration of oral norfloxacin 5-7.5 mg/Kg once a day in cirrhotic patients
      with ascitic fluid protein content of < 1g/dL or prior episode of SBP is
      recommended for prevention of SBP. Oral dual diuretic therapy of single morning
      dose of spironolactone along with furosemide in the ratio of 5:2 is recommended.
      While obtaining satisfactory diuretic response dual diuretic therapy can be
      changed over to monotherapy with spironolactone. Patients should be on sodium
      restricted diet. Management of ascites might ultimately require liver
      transplantation.

PMID- 17006043
TI  - Biliary atresia: outcome and management.
AB  - Untreated, biliary atresia remains a fatal condition of the newborn. Most present
      within four to six weeks of conjugated jaundice and acholic stools and, although
      still a challenging diagnosis to make, therein lies the opportunity of changing
      the course of this otherwise inexorable disease. The aim of surgery is to restore
      bile flow, alleviate jaundice and abbreviate the cholangiodestructive process
      within the liver. The Kasai portoenterostomy, introduced almost 50 years ago in
      Japan, aims to expose microscopic biliary ductules within the fibroinflammatory
      mass at the porta hepatis and restore bile drainage into a mobilised Roux loop.
      About 50% of infants with BA will be able to clear their jaundice following Kasai
      alone, given appropriately experienced surgeons and if performed prior to the
      onset of overt cirrhosis. They have a reasonable expectation of long-term
      survival to adulthood with a good quality-of-life. The remainder may be
      candidates for liver transplantation (where available) although donor organ
      shortage and immunosuppresion-related complications remain significant problems.

PMID- 17006044
TI  - SCIWORA-Spinal Cord Injury Without Radiological Abnormality.
AB  - Following trauma, the commonly used radiological investigations, plain
      radiographs and computed tomography (CT) studies do not rule out injury to the
      spinal cord. This is especially true for children, as an entity known by the
      acronym SCIWORA (spinal cord injury without radiological abnormality) exists and
      the changes may be picked up only on magnetic resonance imaging (MRI). Early
      treatment (within 6 hours) with high dose methylprednisolone improves the
      outcome. Spinal trauma being common it is possible that the burden of
      neurological handicap following this can be reduced by increasing awareness and
      early treatment with steroids. In the community, pediatricians are often the
      first medical contact after spinal trauma and awareness of the lacune of
      conventional imaging techniques is important especially if clinical symptoms
      pertaining to the spine are present. The community pediatrician is hereby made
      aware of the need to investigate spinal trauma with a MRI for possible SCIWORA
      situation as it generates a possibility for therapeutic intervention to alter the
      outcome positively.

PMID- 17006046
TI  - Acute cysticercal meningitis--missed diagnosis.
AB  - Neurocysticercosis is the commonest CNS parasitic disease worldwide but
      cysticercal meningoencephalitis is relatively rare, especially in Indian
      patients. We herein report a girl with cysticercal meningitis that was initially
      not suspected and later diagnosed on the basis of cerebrospinal fluid (CSF)
      eosinophilia. The need for CSF examination with wright-giemsa staining to avoid
      missing CSF eosinophilia is discussed.

PMID- 17006045
TI  - Congenital cystic adenomatoid malformation associated with ipsilateral
      eventration of the diaphragm.
AB  - A two-month-old girl was operated for a left-sided eventration of the diaphragm.
      At surgery, a mass representing an extralobar pulmonary sequestration (EPS) was
      found inferior to the left lobe of the lung and was excised. Histopathological
      examination of the resected specimen showed presence of a type II congenital
      cystic adenomatoid malformation (CCAM) within it. A review of the relevant
      literature is presented.

PMID- 17006047
TI  - Callosal agenesis and Open lip Schizencephaly.
AB  - We report a case of a new born who presented with neonatal seizures; and who had
      coexistence of a Corpus Callosum Agenesis with a bilateral Open lip
      Schizencephaly and a Dandy Walker malformation. The investigations for an
      underlying etiology, however was futile.

PMID- 17006048
TI  - Unbalanced X; autosome translocation.
AB  - Unbalanced X; autosome translocation can result in multiple congenital
      abnormalities/mental retardation syndrome due to chromosomal imbalance. Here is
      described a patient with developmental delay, microcephaly, agenesis of corpus
      callosum, spasticity, seizures and dysmorphism as a result of meiotic
      malsegregation of balanced X; autosome translocation in mother. Present case
      signifies the importance of chromosomal analysis in a patient with developmental
      delay/ mental retardation and discuss lyonization in cases with X; autosome
      translocation.

PMID- 17006049
TI  - Acquired hypothyroidism in an adolescent boy following thyroid surgery.

PMID- 17006050
TI  - Valproate induced isolated neutropenia.

PMID- 17006051
TI  - Carotid artery occlusion and collateral circulation in C57Black/6J mice detected
      by synchrotron radiation microangiography.
AB  - Using monochromatic synchrotron radiation, we performed microangiography in
      C57BL/6J mice and investigated their vasculature after unilateral and bilateral
      carotid artery occlusion. Bilateral occlusion of the carotid artery was made by a
      ligation of the left common carotid artery followed by a ligation of the right
      internal carotid artery (ICA) two days later (n=12). Five days after the second
      surgery, angiography was performed. Unilateral occlusion was made by clipping the
      right ICA and then angiography was performed immediately (n=5). The control mice
      did not undergo any occlusion (n=5). We removed the brain of the bilateral
      occlusion mice after angiography and examined the infarction area. The cerebral
      microvessels in all animals were clearly visualized. In the control mice, the
      posterior communicating artery (Pcom) was not visualized. In the unilateral
      occlusion mice, the anastomosis of the pterygopalatine artery (PPA) and the
      external carotid artery (ECA) were recognized. The PPA is thus considered to play
      a role in the collateral vessel between the ICA and the ECA. The Pcom was not
      visualized. In the bilateral occlusion mice, the Pcom was observed either
      unilaterally (n=5) or bilaterally (n=5). The Pcom supplied blood flow to the
      anterior circulation from the vertebrobasilar arteries. The bilateral occlusion
      mice that had at least one visualized Pcom did not have any infarction. We could
      successfully visualize the cerebral vasculature of normal mice and carotid artery
      occluded mice in an in vivo study. Microangiography can demonstrate the
      development of vasculature and the blood flow dynamics in mice.

PMID- 17006052
TI  - Sca-1 and Thy-1 accelerate neuron-like differentiation in bone marrow stromal
      cells.
AB  - Bone marrow stromal cells taken from EGFP transgenic mice were sorted by magnetic
      beads with surface markers for Sca-1 and Thy-1. The cells were then co-cultured
      on organotypic hippocampal slice or with neuronal cell feeder in dish. On
      hippocampus, both Sca-1 and Thy-1 positive cells showed 4- 8 folds higher
      potential to show neuron-like morphology than negative cells. In dish, negative
      cells fewly survived but each positive cells survived and showed neuron-like
      differentiation. In both culture condition, retinoic acid supplement accelerate
      differentiation. Differentiated Sca-1 and Thy-1 positive cells were
      immunohistochemically GFAP- and NeuN-negative but nestin-, neurofilament- and NSE
      positive. Neuron-like differentiation of bone marrow cells can be enhanced by
      selection using cell surface proteins.

PMID- 17006053
TI  - Analysis of phosphatidylcholine oxidation products in human plasma using
      quadrupole time-of-flight mass spectrometry.
AB  - We report here an application of the previous method for the analysis of
      phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) oxidation products
      in human plasma using quadrupole time of flight (Q-TOF) mass spectrometry with
      electrospray ionization. We separated these products using an HPLC C8 column with
      a gradient of methanol and 10 mM aqueous ammonium acetate. Monohydroperoxides,
      epoxyhydroxy derivatives, oxo derivatives, and trihydroxides of palmitoyl
      linoleoyl (C16:0/C18:2) PC and stearoyl-linoleoyl (C18:0/C18:2) PC were detected
      mainly as MH+ and [M+Na]+ ions in the plasma of alcoholic patients. Using
      standard synthetic PC-OH (C16:0/C18:2-OH), the lipid extract component was
      identified as (C16:0/C18:2-OH) PC based on the product ions of ESI-MS-MS. Using
      standard synthetic PCOOH (C16:0/C18:2-OOH) as a reference, the PCOOH
      concentration in plasma was quantified. Two oxidatively modified lysoPCs were
      also detected. This is the first report showing the presence of epoxyhydroxy
      derivatives, monohydroperoxides, oxo derivatives, and trihydroxides of
      (C16:0/C18:2) PC and (C18:0/C18:2) PC, and PC-OH (C16:0/C18:0-OH) in human
      plasma.

PMID- 17006054
TI  - Protective effect of daidzein against acute ethanol-induced lipid peroxidation in
      rat jejunum.
AB  - Ethanol causes extensive damage to the intestinal tract from the oropharynx to
      the rectum. The jejunum has also been shown to be particularly vulnerable to the
      deleterious effects of ethanol. We hypothesized that (I) the pathogenesis of
      acute alcohol-mediated injury in the small intestine involves generation of
      reactive oxygen species, and consequentially, enhanced lipid peroxidation; (II)
      the pathogenic changes due to alcohol can be ameliorated with daidzein
      pretreatment. To test these hypotheses male Wistar rats (n=24) were divided into
      four groups as follows (pretreatment followed by treatment): [A] carrier+saline
      (control); [B] daidzein+saline; [C] carrier+ethanol; [D] daidzein+ethanol.
      Daidzein (100 mg/kg) or carrier (Intralipid) pretreatment was twice administered
      as a single dose, whereas ethanol (75 mmol/kg) or saline (0.15 mol/l NaCl)
      treatment was administered once only. At 24 h after ethanol or saline was
      administered, rats were sacrificed. The analytes 7alpha-and 7beta
      hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH), 7alpha-and 7beta
      hydroxycholesterol (7alpha-OH and 7beta-OH), and 7-ketocholesterol (7-keto) in
      jejunum were analyzed by HPLC. The data showed that daidzein per se did not
      affect levels of cholesterol hydroperoxides nor oxysterols. However, there were
      significant increases in 7alpha- and 7beta-OOHs, 7alpha- and 7beta-OHs, and 7
      keto after ethanol dosage compared to controls. Daidzein ameliorated these
      effects, i.e., values in the daidzein+ethanol group were similar to those in the
      carrier+saline (control) group. This is the first report showing that (1)
      cholesterol-derived markers of oxidative stress are increased in the rat jejunum
      in response to ethanol, indicative of metabolic damage; (2) daidzein pretreatment
      has protective effects against ethanol-induced injury.

PMID- 17006056
TI  - Postoperative visual loss: experts, data, and practice.

PMID- 17006057
TI  - Retrospective analysis: looking backward to point the way forward.

PMID- 17006058
TI  - Unraveling the mysteries of sleep-disordered breathing in children.

PMID- 17006059
TI  - Regional anesthesia, intraneural injection, and nerve injury: beyond the
      epineurium.

PMID- 17006060
TI  - The American Society of Anesthesiologists Postoperative Visual Loss Registry:
      analysis of 93 spine surgery cases with postoperative visual loss.
AB  - BACKGROUND: Postoperative visual loss after prone spine surgery is increasingly
      reported in association with ischemic optic neuropathy, but its etiology is
      unknown. METHODS: To describe the clinical characteristics of these patients, the
      authors analyzed a retrospectively collected series of 93 spine surgery cases
      voluntarily submitted to the American Society of Anesthesiologists Postoperative
      Visual Loss Registry on standardized data forms. RESULTS: Ischemic optic
      neuropathy was associated with 83 of 93 spine surgery cases. The mean age of the
      patients was 50 +/- 14 yr, and most patients were relatively healthy. Mayfield
      pins supported the head in 16 of 83 cases. The mean anesthetic duration was 9.8
      +/- 3.1 h, and the median estimated blood loss was 2.0 l (range, 0.1-25 l).
      Bilateral disease was present in 55 patients, with complete visual loss in the
      affected eye(s) in 47. Ischemic optic neuropathy cases had significantly higher
      anesthetic duration, blood loss, percentage of patients in Mayfield pins, and
      percentage of patients with bilateral disease compared with the remaining 10
      cases of visual loss diagnosed with central retinal artery occlusion (P < 0.05),
      suggesting they are of different etiology. CONCLUSIONS: Ischemic optic neuropathy
      was the most common cause of visual loss after spine surgery in the Registry, and
      most patients were relatively healthy. Blood loss of 1,000 ml or greater or
      anesthetic duration of 6 h or longer was present in 96% of these cases. For
      patients undergoing lengthy spine surgery in the prone position, the risk of
      visual loss should be considered in the preoperative discussion with patients.

PMID- 17006061
TI  - Can anesthetic technique for primary breast cancer surgery affect recurrence or
      metastasis?
AB  - BACKGROUND: Regional anesthesia is known to prevent or attenuate the surgical
      stress response; therefore, inhibiting surgical stress by paravertebral
      anesthesia might attenuate perioperative factors that enhance tumor growth and
      spread. The authors hypothesized that breast cancer patients undergoing surgery
      with paravertebral anesthesia and analgesia combined with general anesthesia have
      a lower incidence of cancer recurrence or metastases than patients undergoing
      surgery with general anesthesia and patient-controlled morphine analgesia.
      METHODS: In this retrospective study, the authors examined the medical records of
      129 consecutive patients undergoing mastectomy and axillary clearance for breast
      cancer between September 2001 and December 2002. RESULTS: Fifty patients had
      surgery with paravertebral anesthesia and analgesia combined with general
      anesthesia, and 79 patients had general anesthesia combined with postoperative
      morphine analgesia. The follow-up time was 32 +/- 5 months (mean +/- SD). There
      were no significant differences in patients or surgical details, tumor
      presentation, or prognostic factors. Recurrence- and metastasis-free survival was
      94% (95% confidence interval, 87-100%) and 82% (74-91%) at 24 months and 94% (87
      100%) and 77% (68-87%) at 36 months in the paravertebral and general anesthesia
      patients, respectively (P = 0.012). CONCLUSIONS: This retrospective analysis
      suggests that paravertebral anesthesia and analgesia for breast cancer surgery
      reduces the risk of recurrence or metastasis during the initial years of follow
      up. Prospective trials evaluating the effects of regional analgesia and morphine
      sparing on cancer recurrence seem warranted.

PMID- 17006062
TI  - Recurrent hypoxemia in children is associated with increased analgesic
      sensitivity to opiates.
AB  - BACKGROUND: Postsurgical administration of opiates in patients with obstructive
      sleep apnea (OSA) has recently been linked to an increased risk for respiratory
      complications. The authors have attributed this association to an effect of
      recurrent oxygen desaturation accompanying OSA on endogenous opioid mechanisms
      that, in turn, alter responsiveness to subsequent administration of exogenous
      opiates. In a retrospective study, the authors have shown that oxygen
      desaturation and young age in children with OSA are correlated with a reduced
      opiate requirement for postoperative analgesia. METHODS: The current study was
      designed to test that conclusion prospectively in 22 children with OSA scheduled
      to undergo adenotonsillectomy. The children were stratified to those having
      displayed < 85% or > or = 85% oxygen saturation nadir during sleep
      preoperatively. Using a blinded design, the children were given morphine
      postoperatively to achieve an identical behavioral pain score. RESULTS: As
      compared with children in the > or = 85% group, the < 85% oxygen saturation nadir
      group required one half the total analgesic morphine dose postoperatively,
      indicating heightened analgesic sensitivity to morphine after recurrent
      hypoxemia. CONCLUSIONS: Previous recurrent hypoxemia in OSA is associated with
      increased analgesic sensitivity to subsequent morphine administration. Therefore,
      opiate dosing in children with OSA must take into account a history of recurrent
      hypoxemia.

PMID- 17006063
TI  - Decrease of functional residual capacity and ventilation homogeneity after
      neuromuscular blockade in anesthetized young infants and preschool children.
AB  - BACKGROUND: Based on age-dependent differences in pulmonary mechanics, the effect
      of neuromuscular blockade may differ in infants compared with older children. The
      aim of this study was to determine the impact of neuromuscular blockade and its
      reversal by positive end-expiratory pressure (PEEP) on functional residual
      capacity (FRC) and ventilation distribution in young infants and preschool
      children. METHODS: The authors studied 14 infants (aged 0-6 months) and 25
      preschool children (aged 2-6 yr). FRC and lung clearance index were calculated.
      Measurements were taken (1) after intubation, (2) during neuromuscular blockade,
      and (3) during neuromuscular blockade plus application of PEEP (3 cm H2O).
      RESULTS: Functional residual capacity (mean +/- SD) decreased from 21.3 +/- 4.7
      ml/kg to 12.2 +/- 4.8 ml/kg (P < 0.001) during neuromuscular blockade in infants
      and from 25.6 +/- 5.9 ml/kg to 23.0 +/- 5.3 ml/kg (P < 0.001) in preschool
      children. With the application of PEEP, FRC increased to 22.3 +/- 5.9 ml/kg (P =
      0.4829, compared with baseline) in infants and 28.2 +/- 5.8 ml/kg (P < 0.001) in
      children. The lung clearance index increased after neuromuscular blockade,
      whereas baseline values were regained after the application of PEEP. The changes
      induced by neuromuscular blockade were significantly greater in infants compared
      with preschool children (P < 0.001). CONCLUSIONS: Although the use of
      neuromuscular blockade decreased FRC and ventilation distribution substantially
      in both groups, the changes were more pronounced in young infants. With PEEP, FRC
      increased and ventilation homogeneity was restored. These results provide a
      rationale to use PEEP in anesthetized, paralyzed infants and children.

PMID- 17006064
TI  - Quantifying the effect of antiplatelet therapy: a comparison of the platelet
      function analyzer (PFA-100) and modified thromboelastography (mTEG) with light
      transmission platelet aggregometry.
AB  - BACKGROUND: Antiplatelet therapy with aspirin and clopidogrel is known to confer
      protection against ischemic events. Increasing numbers of patients are presenting
      for surgery while taking these drugs. This may lead to an increase in
      perioperative blood loss, particularly in those who have a heightened response to
      the drugs. Identifying these patients preoperatively would allow us to plan
      appropriate management. METHODS: The antiplatelet effect of aspirin and/or
      clopidogrel was measured using two point-of-care monitors: the platelet function
      analyzer (PFA-100; Dade, Miami, FL) and the modified thromboelastograph (mTEG;
      Haemoscope Corp., Niles, IL). This was compared with optical light transmission
      aggregometry. RESULTS: All people taking aspirin displayed a definitive aspirin
      effect on aggregometry (n = 20). Ninety percent of these were identified by
      modified thromboelastography (n = 18). Seventy percent were identified by the
      platelet function analyzer (n = 14). Fifty percent of people taking clopidogrel
      displayed a definitive response to the drug on aggregometry. Seventy percent of
      these were identified on modified thromboelastography (n = 7). None were
      identified by the platelet function analyzer. There was good agreement between
      the results of the aggregometry and modified thromboelastography in clopidogrel
      patients (kappa = 0.81). CONCLUSION: The search for a point-of-care monitor of
      platelet function has been the focus of much research. This study has shown that
      the modified thromboelastograph can be used for monitoring the effect of
      clopidogrel as well as aspirin. It potentially has a wide scope to be used for
      the monitoring of effectiveness of therapy as well as a possible predictor of
      perioperative bleeding.

PMID- 17006065
TI  - Alfentanil dosage when inserting the classic laryngeal mask airway.
AB  - BACKGROUND: The purpose of this study was to determine an optimum dose of
      alfentanil, coadministered with 2.5 mg/kg propofol, when inserting a classic
      laryngeal mask airway. METHODS: Seventy-five adult ethnic Chinese patients with
      an American Society of Anesthesiologists physiologic status classification I or
      II and requiring anesthesia for minor surgery with a laryngeal mask were
      recruited. They were randomly assigned to five dosage groups: placebo or 5, 10,
      15, or 20 microg/kg. The study drug plus propofol were administered, and 90 s
      later, insertion conditions were assessed using a six-category score. The
      duration of apnea was recorded. A probit analysis was performed and used to
      estimate the ED50 and ED95 with 95% confidence intervals for each assessment.
      RESULTS: Twenty-five male and 50 female patients, aged 18-59 yr, were studied.
      The five groups were similar. Laryngeal mask insertion was successful in all but
      one alfentanil patient. Duration of apnea increased with increasing dosage of
      alfentanil to over 5 min (P < 0.001). Dose-responses could not be predicted for
      categories of resistance to mouth opening and to insertion. For the other four
      categories, swallowing, gagging, movement, and laryngospasm, ED50 and ED95 with
      confidence intervals for alfentanil could be determined. CONCLUSION: The optimum
      dose for alfentanil, when coadministered with 2.5 mg/kg propofol, was 10
      microg/kg.

PMID- 17006066
TI  - Mechanical ventilation with lower tidal volumes and positive end-expiratory
      pressure prevents alveolar coagulation in patients without lung injury.
AB  - BACKGROUND: Alveolar fibrin deposition is a hallmark of acute lung injury,
      resulting from activation of coagulation and inhibition of fibrinolysis. Previous
      studies have shown that mechanical ventilation with high tidal volumes may
      aggravate lung injury in patients with sepsis and acute lung injury. The authors
      sought to determine the effects of mechanical ventilation on the alveolar
      hemostatic balance in patients without preexistent lung injury. METHODS: Patients
      scheduled for an elective surgical procedure (lasting > or = 5 h) were randomly
      assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg
      ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal
      volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h
      later bronchoalveolar lavage fluid and blood samples were obtained, and markers
      of coagulation and fibrinolysis were measured. RESULTS: In contrast to mechanical
      ventilation with lower tidal volumes and PEEP (n = 21), the use of higher tidal
      volumes without PEEP (n = 19) caused activation of bronchoalveolar coagulation,
      as reflected by a marked increase in thrombin-antithrombin complexes, soluble
      tissue factor, and factor VIIa after 5 h of mechanical ventilation. Mechanical
      ventilation with higher tidal volumes without PEEP caused an increase in soluble
      thrombomodulin in lavage fluids and lower levels of bronchoalveolar activated
      protein C in comparison with lower tidal volumes and PEEP. Bronchoalveolar
      fibrinolytic activity did not change by either ventilation strategy. CONCLUSIONS:
      Mechanical ventilation with higher tidal volumes and no PEEP promotes
      procoagulant changes, which are largely prevented by the use of lower tidal
      volumes and PEEP.

PMID- 17006067
TI  - Airway management with endotracheal tube versus Combitube during parabolic
      flights.
AB  - BACKGROUND: Training of National Aeronautics and Space Administration space
      shuttle astronauts revealed difficult airway management with endotracheal tubes
      (ETTs) under microgravity conditions. The authors performed a randomized
      comparative study of ETT and Combitube (ETC; Tyco Healthcare, Pleasanton, CA).
      The aim of the study was to evaluate ease, time of insertion, and success rates
      during normogravity and parabolic flights using mannequins. METHODS: After
      normogravity experiments, four flyers performed intubation on a mannequin during
      the flights. Sixty-two intubation attempts were performed using the ETC
      (normogravity, 29; microgravity, 33), and 58 intubation attempts were performed
      using the ETT (each 29 attempts, both conditions). Time to completion of the
      intubation procedure, success rate, and ease of insertion were recorded. RESULTS:
      The ETC performed equally well between normogravity (median, 18 s; range, 17-25
      s) and microgravity (median, 18.5 s; range, 17-28 s), whereas the ETT performed
      significantly slower under microgravity (median, 20 s; range, 17-27 s) as
      compared with normogravity (median, 18 s; range, 16-22 s; P = 0.019). One hundred
      nine of 120 (90%) were successful. The ETT and ETC were comparable with respect
      to successful intubations, under normogravity or microgravity, respectively.
      CONCLUSIONS: Both the ETC and ETT perform comparably well. Slight differences
      could be found with respect to time of insertion in favor of the ETC. Because
      this is the first experiment using the ETC on the KC-135, it is shown that there
      is enough time to perform the insertion procedure. Because the ETC airway
      requires less training and is easier to insert than an ETT, it is recommended for
      further study as an alternative airway to what is currently on the shuttle.

PMID- 17006068
TI  - Short-term cardiorespiratory effects of proportional assist and pressure-support
      ventilation in patients with acute lung injury/acute respiratory distress
      syndrome.
AB  - BACKGROUND: Recent data indicate that assisted modes of mechanical ventilation
      improve pulmonary gas exchange in patients with acute lung injury (ALI)/acute
      respiratory distress syndrome (ARDS). Proportional assist ventilation (PAV) is a
      new mode of support that amplifies the ventilatory output of the patient effort
      and improves patient-ventilator synchrony. It is not known whether this mode may
      be used in patients with ALI/ARDS. The aim of this study was to compare the
      effects of PAV and pressure-support ventilation on breathing pattern,
      hemodynamics, and gas exchange in a homogenous group of patients with ALI/ARDS
      due to sepsis. METHODS: Twelve mechanically ventilated patients with ALI/ARDS
      (mean ratio of partial pressure of arterial oxygen to fractional concentration of
      oxygen 190 +/- 49 mmHg) were prospectively studied. Patients received pressure
      support ventilation and PAV in random order for 30 min while maintaining mean
      airway pressure constant. With both modes, the level of applied positive end
      expiratory pressure (7.1 +/- 2.1 cm H2O) was kept unchanged throughout. At the
      end of each study period, cardiorespiratory data were obtained, and dead space to
      tidal volume ratio was measured. RESULTS: With both modes, none of the patients
      exhibited clinical signs of distress. With PAV, breathing frequency and cardiac
      index were slightly but significantly higher than the corresponding values with
      pressure-support ventilation (24.5 +/- 6.9 vs. 21.4 +/- 6.9 breaths/min and 4.4
      +/- 1.6 vs. 4.1 +/- 1.3 l . min . m, respectively). None of the other parameters
      differ significantly between modes. CONCLUSIONS: In patients with ALI/ARDS due to
      sepsis, PAV and pressure-support ventilation both have clinically comparable
      short-term effects on gas exchange and hemodynamics.

PMID- 17006069
TI  - Risk factors for ventilator-associated pneumonia by Pseudomonas aeruginosa in
      presence of recent antibiotic exposure.
AB  - BACKGROUND: To facilitate the decision-making process for therapy and prevention
      of ventilator-associated pneumonia (VAP) in patients undergoing recent antibiotic
      exposure, this study investigated whether the development of VAP episodes caused
      by Pseudomonas aeruginosa or other pathogens are related to different risk
      factors, thereby distinguishing two risk population for this serious
      complication. METHODS: A 5-year retrospective case-control observational study
      was conducted. Cases of VAP caused by P. aeruginosa were compared with those
      caused by other pathogens. Univariate and multivariate analysis was performed
      using SPSS 11.0 software (SPSS Inc., Chicago, IL). RESULTS: Two groups were
      identified: P. aeruginosa (group P) was isolated in 58 (63.7%) episodes, and 33
      episodes served as controls (group C), after a median of 12 days (interquartile
      range, 4-28 days) and 9 days (interquartile range, 3-12.5 days) of mechanical
      ventilation, respectively. P. aeruginosa was identified in 34.7% of episodes with
      early-onset pneumonia and in 73.5% with late-onset pneumonia. In a logistic
      regression analysis, P. aeruginosa was independently associated with duration of
      stay of 5 days or longer (relative risk = 3.59; 95% confidence interval, 1.04
      12.35) and absence of coma (relative risk = 8.36; 95% confidence interval, 2.68
      26.09). Risk for pathogens different from P. aeruginosa (group C) in early-onset
      pneumonia associated with coma was estimated to be 87.5%. CONCLUSIONS: Risk
      factors in episodes under recent antibiotic treatment caused by P. aeruginosa or
      other microorganism are not the same, a fact that could have implications for
      preventive and therapeutic approaches for this infection.

PMID- 17006070
TI  - Recurrent hypoxia in rats during development increases subsequent respiratory
      sensitivity to fentanyl.
AB  - BACKGROUND: In children with a history of significant obstructive sleep apnea who
      undergo adenotonsillectomy, postsurgical administration of opiates has been
      alleged to be associated with an increased risk for respiratory complications,
      including respiratory depression. The authors hypothesize that this association
      is due to an effect of recurrent hypoxemia that accompanies more severe
      obstructive sleep apnea on altered responsiveness to subsequent exogenous
      opiates. METHODS: The current study was designed to test the effect of recurrent
      hypoxia in the developing rat on respiratory responses to subsequent
      administration of the mu-opioid agonist fentanyl. Rats were exposed to 12% oxygen
      balance nitrogen for 7 h daily for 17 days, from postnatal day 17 to 33, a period
      equivalent to human childhood. After 17 additional days in room air, rats were
      given a fentanyl dose and tested for their respiratory response to fentanyl using
      a whole body plethysmograph. Rats undergoing similar protocols without recurrent
      hypoxia served as controls. RESULTS: As compared with controls, rats preexposed
      to recurrent hypoxia displayed a more profound depression with fentanyl in minute
      ventilation, respiratory frequency, tidal volume, and tidal volume divided by
      inspiratory time that represents respiratory drive. These results indicated an
      increased respiratory sensitivity to fentanyl after recurrent hypoxia.
      CONCLUSIONS: Previous recurrent hypoxia increases respiratory sensitivity to
      subsequent opiate agonists. If these findings are applicable to humans, opiate
      dosing in children must be adjusted depending on history of recurrent hypoxemia
      to avoid respiratory depression.

PMID- 17006071
TI  - Desflurane-induced preconditioning against myocardial infarction is mediated by
      nitric oxide.
AB  - BACKGROUND: Volatile anesthetics induce myocardial preconditioning through a
      signal transduction pathway that is remarkably similar to that observed during
      ischemic preconditioning. Nitric oxide-dependent signaling plays an important
      role in anesthetic and ischemic preconditioning. Therefore, the authors tested
      the hypothesis that desflurane-induced preconditioning is mediated by nitric
      oxide. METHODS: Barbiturate-anesthetized rabbits were instrumented for
      measurement of hemodynamics. All rabbits were subjected to 30-min coronary artery
      occlusion followed by 3 h of reperfusion. Myocardial infarct size was assessed
      with triphenyltetrazolium chloride staining. Myocardial nitric oxide synthase
      activity was assessed with a [H]L-arginine-conversion assay. Rabbits were
      randomized to five separate experimental groups. They received 0.0 or 1.0 minimum
      alveolar concentration desflurane for 30 min, which was discontinued 30 min
      before ischemia in the absence or presence of the nitric oxide synthase inhibitor
      N-nitro-L-arginine (L-NA). L-NA was given either 20 min before or 10 min after
      desflurane administration, respectively. Data are mean +/- SEM. RESULTS: Infarct
      size was 56 +/- 8% in control experiments. Desflurane significantly (P < 0.05)
      reduced infarct size to 35 +/- 4%. Preconditioning by desflurane was totally
      blocked by administration of L-NA either during or after desflurane inhalation
      (58 +/- 4 and 59 +/- 9%, respectively). L-NA alone had no effect on infarct size
      (56 +/- 7%). Nitric oxide synthase activity was significantly (P < 0.05)
      increased by desflurane. CONCLUSION: The results demonstrate that desflurane
      induced preconditioning markedly reduced myocardial infarct size. This beneficial
      effect was blocked by the nitric oxide synthase inhibitor L-NA either during or
      after desflurane-administration. These data suggest that early desflurane-induced
      preconditioning is mediated by nitric oxide.

PMID- 17006072
TI  - New insights into the mechanism of methoxyflurane nephrotoxicity and implications
      for anesthetic development (part 1): Identification of the nephrotoxic metabolic
      pathway.
AB  - BACKGROUND: Methoxyflurane nephrotoxicity results from biotransformation;
      inorganic fluoride is a toxic metabolite. Concern exists about potential renal
      toxicity from volatile anesthetic defluorination, but many anesthetics increase
      fluoride concentrations without consequence. Methoxyflurane is metabolized by
      both dechlorination to methoxydifluoroacetic acid (MDFA, which may degrade to
      fluoride) and O-demethylation to fluoride and dichloroacetatic acid. The
      metabolic pathway responsible for methoxyflurane nephrotoxicity has not, however,
      been identified, which was the aim of this investigation. METHODS: Experiments
      evaluated methoxyflurane metabolite formation and effects of enzyme induction or
      inhibition on methoxyflurane metabolism and toxicity. Rats pretreated with
      phenobarbital, barium sulfate, or nothing were anesthetized with methoxyflurane,
      and renal function and urine methoxyflurane metabolite excretion were assessed.
      Phenobarbital effects on MDFA metabolism and toxicity in vivo were also assessed.
      Metabolism of methoxyflurane and MDFA in microsomes from livers of pretreated
      rats was determined in vitro. RESULTS: Phenobarbital pretreatment increased
      methoxyflurane nephrotoxicity in vivo (increased diuresis and blood urea nitrogen
      and decreased urine osmolality) and induced in vitro hepatic microsomal
      methoxyflurane metabolism to inorganic fluoride (2-fold), dichloroacetatic acid
      (1.5-fold), and MDFA (5-fold). In contrast, phenobarbital had no influence on
      MDFA renal effects in vivo or MDFA metabolism in vitro or in vivo. MDFA was
      neither metabolized to fluoride nor nephrotoxic. Barium sulfate diminished
      methoxyflurane metabolism and nephrotoxicity in vivo. CONCLUSIONS: Fluoride from
      methoxyflurane anesthesia derives from O-demethylation. Phenobarbital increases
      in methoxyflurane toxicity do not seem attributable to methoxyflurane
      dechlorination, MDFA toxicity, or MDFA metabolism to another toxic metabolite,
      suggesting that nephrotoxicity is attributable to methoxyflurane O-demethylation.
      Fluoride, one of many metabolites from O-demethylation, may be toxic and/or
      reflect formation of a different toxic metabolite. These results may have
      implications for interpreting anesthetic defluorination, volatile anesthetic use,
      and methods to evaluate anesthetic toxicity.

PMID- 17006073
TI  - New insights into the mechanism of methoxyflurane nephrotoxicity and implications
      for anesthetic development (part 2): Identification of nephrotoxic metabolites.
AB  - BACKGROUND: Methoxyflurane nephrotoxicity results from its metabolism, which
      occurs by both dechlorination (to methoxydifluoroacetic acid [MDFA]) and O
      demethylation (to fluoride and dichloroacetic acid [DCAA]). Inorganic fluoride
      can be toxic, but it remains unknown why other anesthetics, commensurately
      increasing systemic fluoride concentrations, are not toxic. Fluoride is one of
      many methoxyflurane metabolites and may itself cause toxicity and/or reflect
      formation of other toxic metabolite(s). This investigation evaluated the
      disposition and renal effects of known methoxyflurane metabolites. METHODS: Rats
      were given by intraperitoneal injection the methoxyflurane metabolites MDFA,
      DCAA, or sodium fluoride (0.22, 0.45, 0.9, or 1.8 mmol/kg followed by 0.11, 0.22,
      0.45, or 0.9 mmol/kg on the next 3 days) at doses relevant to metabolite exposure
      after methoxyflurane anesthesia, or DCAA and fluoride in combination. Renal
      histology and function (blood urea nitrogen, urine volume, urine osmolality) and
      metabolite excretion in urine were assessed. RESULTS: Methoxyflurane metabolite
      excretion in urine after injection approximated that after methoxyflurane
      anesthesia, confirming the appropriateness of metabolite doses. Neither MDFA nor
      DCAA alone had any effects on renal function parameters or necrosis. Fluoride at
      low doses (0.22, then 0.11 mmol/kg) decreased osmolality, whereas higher doses
      (0.45, then 0.22 mmol/kg) also caused diuresis but not significant necrosis.
      Fluoride and DCAA together caused significantly greater tubular cell necrosis
      than fluoride alone. CONCLUSIONS: Methoxyflurane nephrotoxicity seems to result
      from O-demethylation, which forms both fluoride and DCAA. Because their co
      formation is unique to methoxyflurane compared with other volatile anesthetics
      and they are more toxic than fluoride alone, this suggests a new hypothesis of
      methoxyflurane nephrotoxicity. This may explain why increased fluoride formation
      from methoxyflurane, but not other anesthetics, is associated with toxicity.
      These results may have implications for the interpretation of clinical anesthetic
      defluorination, use of volatile anesthetics, and the laboratory methods used to
      evaluate potential anesthetic toxicity.

PMID- 17006074
TI  - Adding bupivacaine to high-potassium cardioplegia improves function and reduces
      cellular damage of rat isolated hearts after prolonged, cold storage.
AB  - BACKGROUND: Bupivacaine retards myocardial acidosis during ischemia. The authors
      measured function of rat isolated hearts after prolonged storage to determine
      whether bupivacaine improves cardiac protection compared with standard
      cardioplegia alone. METHODS: After measuring cardiac function on a Langendorff
      apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia
      containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine;
      were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and
      left ventricular developed pressures were measured for 60 min. Maximum positive
      rate of change in ventricular pressure, oxygen consumption, and lactate
      dehydrogenase release were also measured. RESULTS: All bupivacaine-treated, four
      of five lidocaine-treated, and no control hearts beat throughout the 60-min
      recovery period. Mean values of heart rate, left ventricular developed pressure,
      maximum positive rate of change in ventricular pressure, rate-pressure product,
      and efficiency in bupivacaine-treated hearts exceeded those of the control group
      (P < 0.001 at 60 min for all). Mean values of the lidocaine group were
      intermediate. Oxygen consumption of the control group exceeded the other groups
      early in recovery, but not at later times. Lactate dehydrogenase release from the
      bupivacaine group was less than that from the control group (P < 0.001) but did
      not differ from baseline. CONCLUSIONS: Adding bupivacaine to a depolarizing
      cardioplegia solution reduces cell damage and improves cardiac function after
      prolonged storage. Metabolic inhibition may contribute to this phenomenon, which
      is not entirely explained by sodium channel blockade.

PMID- 17006075
TI  - Different inhibitory effects of sevoflurane on hyperreactive airway smooth muscle
      contractility in ovalbumin-sensitized and chronic cigarette-smoking guinea pig
      models.
AB  - BACKGROUND: The authors hypothesized that sevoflurane had different inhibitory
      effects on hyperreactive airway smooth muscle contractility in different types of
      hyperreactive airway models. METHODS: The effects of sevoflurane on hyperreactive
      airways in ovalbumin-sensitized and chronic cigarette-smoking guinea pig models
      were investigated by measuring (1) total lung resistance, (2) smooth muscle
      tension and intracellular concentration of free Ca, (3) voltage-dependent Ca
      channel activity, and (4) cyclic adenosine monophosphate levels. RESULTS:
      Ovalbumin and muscarinic airway hyperreactivity was seen in ovalbumin-sensitized
      animals. Enlarged alveolar ducts/alveoli and lesser muscarinic hyperreactivity
      were observed in chronic cigarette-smoke animals. Although sevoflurane inhibited
      the acetylcholine-induced increase in total lung resistance in the control and
      ovalbumin-sensitized models, the anesthetic had a smaller effect in the chronic
      cigarette-smoking model. Similarly, in the chronic cigarette-smoking model,
      sevoflurane had a smaller inhibitory effect on carbachol-induced muscle
      contraction and increase in intracellular concentration of free Ca. Sevoflurane
      also had a smaller inhibitory effect on voltage-dependent Ca channel activity in
      the chronic cigarette-smoking group than in the other two groups. The sevoflurane
      induced increase in cyclic adenosine monophosphate that was seen in the control
      and ovalbumin-sensitized groups was significantly suppressed in the chronic
      cigarette-smoking group. CONCLUSIONS: Although sevoflurane potently inhibited
      airway contractility in control and ovalbumin-sensitized models, the anesthetic
      had a smaller effect in a chronic cigarette-smoking model. The different
      inhibitory effects of sevoflurane on airway contractility depend, at least in
      part, on different effects on voltage-dependent Ca channel activity and cyclic
      adenosine monophosphate level.

PMID- 17006076
TI  - Supraspinal anesthesia: behavioral and electroencephalographic effects of
      intracerebroventricularly infused pentobarbital, propofol, fentanyl, and
      midazolam.
AB  - BACKGROUND: Anesthetic endpoints of unconsciousness and immobility result from
      agent effects on both brain and spinal cord that are difficult to separate during
      systemic administration. To investigate cerebral mechanism of anesthetic-induced
      unconsciousness, the authors studied behavioral and electrophysiologic effects of
      four anesthetics infused intracerebroventricularly to conscious rats. The authors
      aimed to produce progressively increasing anesthetic depths, indicated by electro
      encephalographic synchronization and behavioral change. METHODS: During
      anesthesia, rats were equipped with intracerebroventricular infusion catheters,
      hind-paw stimulation, and epidural electrodes to record the electroencephalogram
      from the somatosensory cortex. Silicone bolus was injected into the fourth
      ventricle to minimize drug distribution to the spinal cord. 60 min later, 50-min
      infusion of pentobarbital (6.0 mg/h), fentanyl (0.75 microg/h), propofol (3.0
      mg/h), or midazolam (0.24 mg/h) was initiated. Vibrissal, olfactory, corneal, and
      tail-pinch responses were tested every 10 min. RESULTS: All agents depressed
      vibrissal, olfactory, and corneal responses; propofol and pentobarbital produced
      the strongest effect. All agents except propofol depressed tail-pinch response;
      fentanyl and pentobarbital produced the strongest effect. All agents except
      midazolam increased delta power. Pentobarbital enhanced theta power. All agents
      except fentanyl enhanced alpha and beta power. Pentobarbital and midazolam
      slightly increased, whereas fentanyl decreased, gamma power. Pentobarbital
      increased and midazolam decreased somatosensory evoked potential; these changes
      were small and apparently unrelated to behavior. CONCLUSIONS: Alpha and beta
      power increase may reflect sedative component of anesthesia. Simultaneous delta,
      alpha, and beta power increase may correlate with loss of consciousness. Theta
      and delta power increase may reflect surgical anesthesia. Opioid-induced gamma
      power decrease may reflect suppression of pain perception. Pentobarbital-,
      fentanyl-, and midazolam-induced immobility to noxious stimulation may be
      mediated supraspinally.

PMID- 17006077
TI  - Nerve puncture and apparent intraneural injection during ultrasound-guided
      axillary block does not invariably result in neurologic injury.
AB  - BACKGROUND: Nerve puncture by the block needle and intraneural injection of local
      anesthetic are thought to be major risk factors leading to neurologic injury
      after peripheral nerve blocks. In this study, the author sought to determine the
      needle-nerve relation and location of the injectate during ultrasound-guided
      axillary plexus block. METHODS: Using ultrasound-guided axillary plexus block (10
      MHz linear transducer, SonoSite, Bothel, WA; 22-gauge B-bevel needle, Becton
      Dickinson, Franklin Parks, NJ), the incidence of apparent nerve puncture and
      intraneural injection of local anesthetic was prospectively studied in 26
      patients. To determine the onset, success rate, and any residual neurologic
      deficit, qualitative sensory and quantitative motor testing were performed before
      and 5 and 20 min after block placement. At a follow-up 6 months after the blocks,
      the patients were examined for any neurologic deficit. RESULTS: Twenty-two of 26
      patients had nerve puncture of at least one nerve, and 21 of 26 patients had
      intraneural injection of at least one nerve. In the entire cohort, 72 of a total
      of 104 nerves had intraneural injection. Sensory and motor testing before and 6
      months after the nerve injections were unchanged. CONCLUSIONS: Under the
      conditions of this study, puncturing of the peripheral nerves and apparent
      intraneural injection during axillary plexus block did not lead to a neurologic
      injury.

PMID- 17006078
TI  - Postoperative analgesia after radical retropubic prostatectomy: a double-blind
      comparison between low thoracic epidural and patient-controlled intravenous
      analgesia.
AB  - BACKGROUND: Postoperative pain after radical retropubic prostatectomy can be
      severe unless adequately treated. Low thoracic epidural analgesia and patient
      controlled intravenous analgesia were compared in this double-blind, randomized
      study. METHODS: Sixty patients were randomly assigned to receive either low
      thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia
      (group P) for postoperative pain relief. All patients had general anesthesia
      combined with thoracic epidural analgesia during the operation. Postoperatively,
      patients in group E received an infusion of 1 mg/ml ropivacaine, 2 microg/ml
      fentanyl, and 2 microg/ml adrenaline, 10 ml/h during 48 h epidurally, and a
      placebo patient-controlled intravenous analgesia pump intravenously. Patients in
      group P received a patient-controlled intravenous analgesia pump with morphine
      intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable,
      was measured using the numeric rating scale at rest (incision pain and "deep"
      visceral pain) and on coughing. Secondary outcome variables included
      gastrointestinal function, respiratory function, mobilization, and full recovery.
      Health-related quality of life was measured using the Short Form-36
      questionnaire, and plasma concentration of fentanyl was measured in five patients
      to exclude a systemic effect of fentanyl. RESULTS: Incisional pain and pain on
      coughing were lower in group E compared with group P at 2-24 h, as was deep pain
      between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was
      greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference
      in time to home discharge was found between the groups. The mean plasma fentanyl
      concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1
      month, the scores on emotional role, physical functioning, and general health of
      the Short Form-36 were higher in group E compared with group P. However, no group
      x time interaction was found in the Short Form-36. CONCLUSIONS: The authors found
      evidence for better pain relief and improved expiratory muscle function in
      patients receiving low thoracic epidural analgesia compared with patient
      controlled analgesia for radical retropubic prostatectomy. Low thoracic epidural
      analgesia can be recommended as a good method for postoperative analgesia after
      abdominal surgery.

PMID- 17006079
TI  - Pain after cardiac surgery: a prospective cohort study of 1-year incidence and
      intensity.
AB  - BACKGROUND: Persistent chest pain may originate from cardiac surgery. Conflicting
      results have been reported on the incidence of persistent poststernotomy pain
      with considerable discrepancies between the retrospective reports and the one
      prospective study conducted to assess this pain. Therefore, the authors conducted
      a follow-up survey for the first 12 months after cardiac surgery in 213 patients
      who had a sternotomy. METHODS: The authors performed a prospective inquiry of
      acute and chronic poststernotomy pain both before and after cardiac surgery. Two
      hundred thirteen coronary artery bypass patients received a questionnaire
      preoperatively, 4 days postoperatively, and 1, 3, 6, and 12 months
      postoperatively. All patients were asked about their expectations, their
      preferences, and the location and intensity of postoperative pain. RESULTS: The
      return rates for the postal questionnaires were 203 (95%) and 186 (87%) after 1
      and 12 months, respectively. Patients experienced more pain postoperatively at
      rest than they had expected to preoperatively. At rest, the worst actual
      postoperative pain was 6 (0-10), and the worst expected pain as assessed
      preoperatively was 5 (0-10) (P = 0.013). The worst reported postoperative pain
      was severe (numeric rating scale score 7-10) in 49% at rest, in 78% during
      coughing, and in 62% of patients on movement. One year after the operation, 26
      patients (14%) reported mild chronic poststernotomy pain at rest, 1 patient (1%)
      had moderate pain, and 3 patients (2%) had severe pain. Upon movement, persistent
      pain was even more common: 45 patients (24%) had mild, 5 patients (3%) had
      moderate, and 7 patients (4%) had severe pain. Patients who experienced moderate
      to severe acute postoperative pain also reported any chronic poststernotomy pain
      (numeric rating scale score 1-10) more frequently. CONCLUSIONS: Although common,
      the incidence of persistent pain after sternotomy was lower than previously
      reported. Also, reassuringly, 1 year after surgery this pain was mostly mild in
      nature both at rest and on movement.

PMID- 17006080
TI  - Antinociception by spinal and systemic oxycodone: why does the route make a
      difference? In vitro and in vivo studies in rats.
AB  - BACKGROUND: The pharmacology of oxycodone is poorly understood despite its
      growing clinical use. The discrepancy between its good clinical effectiveness
      after systemic administration and the loss of potency after spinal administration
      led the authors to study the pharmacodynamic effects of oxycodone and its
      metabolites using in vivo and in vitro models in rats. METHODS: Male Sprague
      Dawley rats were used in hot-plate, tail-flick, and paw-pressure tests to study
      the antinociceptive properties of morphine, oxycodone, and its metabolites
      oxymorphone and noroxycodone. Mu-opioid receptor agonist-stimulated GTPgamma[S]
      autoradiography was used to study G-protein activation induced by morphine,
      oxycodone, and oxymorphone in the rat brain and spinal cord. Spontaneous
      locomotor activity was measured to assess possible sedation or motor dysfunction.
      Naloxone and the selective kappa-opioid receptor antagonist nor-binaltorphimine
      were used to study the opioid receptor selectivity of the drugs. RESULTS:
      Oxycodone showed lower efficacy and potency to stimulate GTPgamma[S] binding in
      the spinal cord and periaqueductal gray compared with morphine and oxymorphone.
      This could relate to the fact that oxycodone produced only weak naloxone
      reversible antinociception after intrathecal administration. It also suggests
      that the metabolites may have a role in oxycodone-induced analgesia in rats.
      Intrathecal oxymorphone produced strong long-lasting antinociception, whereas
      noroxycodone produced antinociception with very high doses only. Subcutaneous
      administration of oxycodone and oxymorphone produced thermal and mechanical
      antinociception that was reversed by naloxone but not by nor-binaltorphimine.
      Oxymorphone was more potent than oxycodone, particularly in the hot-plate and paw
      pressure tests. CONCLUSIONS: The low intrathecal potency of oxycodone in rats
      seems be related to its low efficacy and potency to stimulate mu-opioid receptor
      activation in the spinal cord.

PMID- 17006081
TI  - Severe toxic damage to the rabbit spinal cord after intrathecal administration of
      preservative-free S(+)-ketamine.
AB  - BACKGROUND: Ketamine and S(+)-ketamine have been advocated for neuraxial use in
      the management of postoperative pain and severe intractable pain syndromes
      unresponsive to opioid escalation. Although clinical experience has accumulated
      with S(+)-ketamine, safety data on toxicity in the central nervous system after
      neuraxial administration of S(+)-ketamine are conflicting. In this study,
      neurologic and toxicologic effects on the spinal cord from repeated daily
      intrathecal administration of commercially available, preservative-free S(+)
      ketamine were evaluated against placebo in a randomized, blinded design. METHODS:
      Eighteen white New Zealand rabbits were assigned to two groups receiving either
      0.5 ml intrathecal S(+)-ketamine, 0.5% solution (12 rabbits), or 0.5 ml saline (6
      rabbits) once a day for 7 consecutive days. During general anesthesia, an
      intrathecal catheter was placed between the fifth and sixth spinous processes
      (lumbar). Neurologic (according to Tarlov criteria) and histopathologic
      assessments were performed after 7 days of treatment. RESULTS: Postmortem
      investigation of the spinal cord and nerve roots revealed histopathologic lesions
      suggestive of toxic damage in 11 rabbits, from the group of 12 animals receiving
      S(+)-ketamine. These results were significantly different compared with 5 control
      animals (no histologic changes observed). There was no significant difference in
      neurologic status between the two groups after 7 days of intrathecal treatment.
      CONCLUSIONS: The authors conclude that repeated intrathecal administration of
      preservative-free S(+)-ketamine in a clinically relevant concentration and dosage
      has, considering the extent and severity of the lesions, a toxic effect on the
      central nervous system of rabbits.

PMID- 17006082
TI  - Clinical implications of mitochondrial dysfunction.
AB  - Mitochondria produce metabolic energy, serve as biosensors for oxidative stress,
      and eventually become effector organelles for cell death through apoptosis. The
      extent to which these manifold mitochondrial functions are altered by previously
      unrecognized actions of anesthetic agents seems to explain and link a wide
      variety of perioperative phenomena that are currently of interest to
      anesthesiologists from both a clinical and a scientific perspective. In addition,
      many surgical patients may be at increased perioperative risk because of
      inherited or acquired mitochondrial dysfunction leading to increased oxidative
      stress. This review summarizes the essential aspects of the bioenergetic process,
      presents current knowledge regarding the effects of anesthetics on mitochondrial
      function and the extent to which mitochondrial state determines anesthetic
      requirement and potential anesthetic toxicity, and considers some of the many
      implications that our knowledge of mitochondrial dysfunction poses for anesthetic
      management and perioperative medicine.

PMID- 17006083
TI  - Written in granite: a history of the Ether Monument and its significance for
      anesthesiology.

PMID- 17006085
TI  - Wernicke encephalopathy: a complication of parenteral nutrition diagnosed by
      magnetic resonance imaging.

PMID- 17006084
TI  - Methoxyflurane revisited: tale of an anesthetic from cradle to grave.
AB  - Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. By
      Richard I. Mazze, James R. Trudell, and Michael J. Cousins. Anesthesiology 1971;
      35:247-52. Reprinted with permission. Serum inorganic fluoride concentration and
      urinary inorganic fluoride excretion were found to be markedly elevated in ten
      patients previously shown to have methoxyflurane induced renal dysfunction. Five
      patients with clinically evident renal dysfunction had a mean peak serum
      inorganic fluoride level (190 +/- 21 microm) significantly higher (P < 0.02) than
      that of those with abnormalities in laboratory tests only (106 +/- 17 microm).
      Similarly, patients with clinically evident renal dysfunction had a mean peak
      oxalic acid excretion (286 +/- 39 mg/24 h) significantly greater (P < 0.05) than
      that of those with laboratory abnormalities only (130 +/- 51 mg/24 h). That
      patients anesthetized with halothane had insignificant changes in serum inorganic
      fluoride concentration and oxalic acid excretion indicates that these substances
      are products of methoxyflurane metabolism. A proposed metabolic pathway to
      support this hypothesis is presented, as well as evidence to suggest that
      inorganic fluoride is the substance responsible for methoxyflurane renal
      dysfunction.

PMID- 17006086
TI  - Compression of the subarachnoid space by the engorged epidural venous plexus in
      pregnant women.

PMID- 17006088
TI  - Good ideas deserve repeating.

PMID- 17006089
TI  - Thoracic epidural anesthesia/analgesia for cardiac surgery: don't put down your
      Tuohy needles yet.

PMID- 17006091
TI  - Thoracic epidural analgesia after cardiac surgery.

PMID- 17006092
TI  - Improving the success of retrograde tracheal intubation.

PMID- 17006093
TI  - In line with the ultrasound beam, the third dimension to ultrasound-guided nerve
      blocks.

PMID- 17006097
TI  - Ultrasound is not the only technique to visualize third occipital nerve blockade.

PMID- 17006098
TI  - Key components of risk associated with ophthalmic anesthesia.

PMID- 17006099
TI  - Pseudothrombus in the aorta.

PMID- 17006100
TI  - Light wand: showing the way.

PMID- 17006102
TI  - Neuromuscular blockade monitoring complicated by the unknown preoperative
      cosmetic use of botulinum toxin.

PMID- 17006101
TI  - An alternative approach to ganglion impar neurolysis under computed tomography
      guidance for recurrent vulva cancer.

PMID- 17006105
TI  - Course of the fatigue dimension "activity level" and the interference of fatigue
      with daily living activities for patients with breast cancer receiving adjuvant
      chemotherapy.
AB  - The purpose of this study was to determine the course of the activity level, seen
      as a dimension of fatigue, as a function of chemotherapy within a breast cancer
      population receiving adjuvant chemotherapy. The second purpose of this study was
      to determine the course of the interference of fatigue, in general, with daily
      activities within a breast cancer population receiving adjuvant chemotherapy. In
      a prospective cohort study, a sample of 157 patients with breast cancer was
      interviewed, at the first, third, and fifth cycle of adjuvant chemotherapy as
      well as 4 and 12 weeks after the last cycle of adjuvant chemotherapy. The
      chemotherapy was administered with either a doxorubicin-containing schedule or
      cyclophosphamide, methotrexate, and 5-fluorouracil. These 2 groups were compared.
      The activity level was measured by the Multidimensional Fatigue Inventory. A
      linear multilevel model was used to analyze the course. The revised Piper Fatigue
      Scale was used to examine the behavioral changes in the interference of fatigue
      with activities of daily living. A logistic multilevel model was used to analyze
      the course of this interference over time. The activity level seems to be rather
      stable during the treatment with chemotherapy. After the completion of
      chemotherapy, an improvement is observed. The activity levels reported at the
      first and the last measurement do not significantly differ. The course of the
      activity level is not affected by the type of chemotherapy regimen. Age, having
      children, and the stage of breast cancer turn out to be important determinants of
      the course of activity level. At all measurement occasions, women with a
      mastectomy were significantly more hampered in their activity level than women
      that had undergone a lumpectomy. The longer the duration of radiotherapy, the
      less active, and the longer the time interval between the last radiotherapy
      session and the measurement point, the more active patients were at that
      measurement point. A phenomenon not easy to explain is that the activity level in
      women who had received, in total, more chemotherapy treatments was significantly
      less diminished than those who had received fewer treatments. During the study
      period, in approximately 15% to 35% of the sample, fatigue interferes
      considerably with their daily living activities. Furthermore, the interference of
      fatigue with activities in daily life first increases after the start of
      chemotherapy and decreases after the completion of chemotherapy. Fatigue
      definitely affects the daily living activities of patients with breast cancer
      receiving adjuvant chemotherapy. With this knowledge, healthcare providers can
      inform patients on what they can expect. Further research should include the
      trajectory preceding chemotherapy and a healthy control group.

PMID- 17006106
TI  - Chinese-Australian women's beliefs about cancer: implications for health
      promotion.
AB  - Ethnicity and culture play significant roles in determining how an individual is
      likely to understand and explain cancer, which, in turn, is posited to have an
      impact on cancer screening behavior. Chinese women in Western countries are
      consistently reported to have low participation rates in mammographic screening.
      This may be related to the fact that women of Chinese ancestry have different
      images and beliefs about cancer, which can have implications for participation in
      health promotion programs regarding cancer prevention and early detection. To
      investigate this issue, a qualitative study involving in-depth interviews with 20
      Chinese-Australian women was conducted. Embedded in the women's images of cancer
      were notions associated with fear, mystery, contagion, and stigma. Based on
      information provided by the women who participated in this study, 6 domains of
      folk explanations about the causes of cancer were identified: lifestyle, stress,
      environment, genes, unknown causes, and destiny. These beliefs should be
      considered in the design of breast health promotion programs because they are
      likely to have a bearing on Chinese-Australian women's attitudes regarding the
      value they perceive of cancer screening.

PMID- 17006107
TI  - Cancer treatment, symptom monitoring, and self-care in adults: pilot study.
AB  - A descriptive study was conducted on self-reported symptoms and self-care by 37
      adults receiving chemotherapy primarily for leukemia, lymphomas, or breast cancer
      or radiation therapy for head and neck or lung cancers. The Therapy-Related
      Symptom Checklist and demographic and interview forms on self-care for identified
      symptoms were used. Severe symptoms on the Therapy-Related Symptom Checklist
      subscales fatigue, eating, nausea, pain, numbness in fingers/toes, hair loss, and
      constipation were reported by patients on chemotherapy. Those on radiation
      therapy reported severe symptoms on the eating, fatigue, skin changes,
      oropharynx, and constipation subscales.Self-care strategies were in the following
      categories, using complementary medicine as framework: diet/nutrition/lifestyle
      change (eg, use of nutritional supplements; modifications of food and of eating
      habits; naps, sleep, and rest); mind/body control (eg, relaxation methods,
      prayer, music, attending granddaughter's sports events); biologic treatments
      (vitamins); herbal treatments (green mint tea); and ethnomedicine (lime juice and
      garlic). The first category was predominantly used by patients in both treatment
      types. Medications were prescribed also to help control symptoms (eg, pain and
      nausea). Symptom monitoring and self-care for symptoms identified may be
      facilitated by the Therapy-Related Symptom Checklist; based on reported symptom
      severity, care providers may prioritize interventions. A larger study needs to be
      done on (a) the use of the Therapy-Related Symptom Checklist as a clinical tool
      to assess symptoms that oncology patients experience during therapy; (b) whether
      care providers, based on patient-reported symptom severity, can prioritize
      interventions--and how this influences the efficiency of care; (c) the self-care
      strategies used by patients on chemotherapy or radiation therapy or both; and (d)
      how useful these strategies are in alleviating symptoms.

PMID- 17006108
TI  - Hope and related variables in Italian cancer patients.
AB  - Hope, long considered an essential element for life, has been shown to be
      important among cancer patients in coping, perceived control over the illness,
      and psychologic adjustment to the illness. The purpose of this study was (a) to
      describe the level of hope in Italian cancer patients; (b) to compare the levels
      of hope during and after hospitalization; (c) to determine whether hope was
      correlated with quality of life and several symptoms; and (d) to determine
      whether the variables from the international literature also pertain to Italian
      cancer patients. A descriptive correlational design using repeated measures was
      chosen to study 80 Italian cancer patients during hospitalization and then at
      home. The following instruments were used: a Sociodemographic Questionnaire, the
      Hope Related Variable Questionnaire, the Nowotny Hope Scale, the Rotterdam
      Symptom Checklist, and the Hospital Anxiety and Depression Scale. Overall,
      patients were moderately hopeful and the level of hopefulness was similar in the
      hospital and at home. Hope was positively correlated with quality of life, self
      esteem, coping, adjustment to the illness, well-being, comfort in the hospital,
      satisfaction with information received, relationship with, and support from
      family, healthcare professional, and friends. Hope was negatively correlated with
      anxiety, depression, and boredom during hospitalization. Time since diagnosis,
      illness stage, and knowing or not knowing the diagnosis and treatment were not
      correlated with hope. Similarities and differences with the international
      literature are discussed, and implications for caring for Italian cancer patients
      are drawn.

PMID- 17006110
TI  - Qualitative analysis of couples' experience with prostate cancer by age cohort.
AB  - Prostate cancer is a significant cause of morbidity and mortality in men in all
      adult life stages. Normative developmental tasks of aging combined with disease
      related stressors may negatively affect adjustment to prostate cancer and,
      consequently, affect the quality of life of both the man and his spouse. The
      purpose of this study was to examine the experiences of men with prostate cancer
      and their partners according to their life cycle cohort: 50-64 (late middle age),
      65-74 (young-old), and 75-84 (old-old). Qualitative interviews with 15 couples
      were used to provide information about the dyad's experiences with prostate
      cancer. Interview data were analyzed to identify preliminary coding schemas,
      which were subsequently refined and modified into themes. Three major themes were
      identified from the data. Across all age groups, prostate cancer had a
      significant effect on: (1) couples' daily lives, (2) their dyadic and family
      relationships, and (3) their developmental stage. There were also differences in
      age groups. Couples in the late middle age group reported greater disappointment
      and anger at their inability to reach life goals and establish financial
      security. Couples in the young-old group made more spontaneous comments about
      being satisfied with their life than the couples in the other 2 groups. Couples
      in the old-old group reported slower recovery from the illness than the younger
      couples. Results indicate that although prostate cancer may have some universal
      effects on couples, it also may have differential effects by age cohort. Hence,
      targeted interventions by age cohort may be warranted.

PMID- 17006111
TI  - Problems experienced by the informal caregivers of cancer patients and their
      needs for support.
AB  - Informal caregivers experience problems of their own for which they need support,
      but despite the efforts of the World Health Organization to include the well
      being of family members and caregivers in the concept of palliative care, their
      needs are rarely assessed systematically. This report explores caregivers'
      problems and their needs for professional support. Seventy-six caregivers of
      cancer patients with advanced disease completed a comprehensive needs assessment
      questionnaire, the Problems and Needs in Palliative Care questionnaire-caregiver
      form, listing 67 potential problems in their quality of life and their role of
      caregiver and 9 items concerning informational needs. The results of this study
      reveal that the "Top 20" list of the problems and needs reported by caregivers
      includes fears and emotional burdens; for the most part, caregivers did not need
      any more professional attention than they were already receiving. Many, however,
      needed support for managing patients' symptoms and wanted professional attention
      for the availability and coordination of services. Despite communalities, there
      was diversity in caregivers' individual needs. Personal needs could be identified
      with the Problems and Needs in Palliative Care questionnaire-caregiver form
      checklist. Although only a few caregivers were affected by some issues, such as
      financial problems, help for them was often needed. In conclusion, most
      caregivers would like more professional attention for 4 or 5 specific issues,
      often related to their competence as caregivers for their patients. Using
      structured needs assessments with the Problems and Needs in Palliative Care
      questionnaire-caregiver form seems a feasible method to identify the needs of
      individual caregivers in palliative care.

PMID- 17006113
TI  - Living with incurable cancer at the end of life--patients' perceptions on quality
      of life.
AB  - This study describes incurably ill cancer patients' perceptions of the quality of
      life at the end of life. Purposeful sampling was used to get as comprehensive
      descriptions as possible about quality of life. Five patients participated in
      repeated focus groups. Content analysis showed that the patients emphasized what
      they could perform and enjoy in daily life, not their shortcomings. Five themes
      were developed: "valuing ordinariness in life," "maintaining a positive life,"
      "alleviated suffering," "significant relations," and "managing life when ill."
      The themes describe that the patients could participate in daily and social life
      despite cancer. Relation with family and palliative team deepened during the
      progress of illness in such that a resonance developed in communication. Other
      important findings were that patients' memories helped them to maintain a
      positive life and that the patients used individual strategies to relieve pain by
      emotional and physical distractions. For the patients, managing life as ill meant
      taking actions with creative thinking in solving problems as a way to cope and
      achieve quality of life. These positive findings from the focus groups have led
      to continued research regarding how patients with incurable cancer perceive
      quality of life.

PMID- 17006115
TI  - Siblings' experiences with childhood cancer: a different way of being in the
      family.
AB  - Childhood cancer and its treatment result in many challenges that impact the
      entire family. For siblings of children with cancer, the challenges can be
      particularly stressful as they often undergo tremendous change in their lives.
      Although there is a sound and growing body of knowledge on how siblings
      experience childhood cancer, there is still much to be learned. Part of a larger
      qualitative study aimed at detailing childhood cancer experience and its symptom
      trajectory from the perspective of parents, ill children, and siblings, this
      study aims to describe findings specific to 30 siblings who participated in the
      study. Siblings took part in individual interviews, focus group interviews, and
      participant observation. The constant comparative method of data analysis yielded
      the theoretical category of "ways of being in the world," which referred to the
      different ways that cancer impacted on the lives of children with cancer and
      their families. For the siblings, cancer was experienced as a different way of
      being within their family and involved siblings undergoing a loss of a family way
      of life and a loss of self within the family. Three themes related to a different
      way of being in the family were identified: committing to keeping my family
      together, being present, and enduring sadness. The findings reinforce that more
      needs to be done in helping healthy siblings through childhood cancer.

PMID- 17006114
TI  - Psychological distress of patients with advanced cancer: influence and
      contribution of pain severity and pain interference.
AB  - The growing interest in the psychological distress and the multidimensionality of
      pain in patients with cancer has been the major reason for the conduction of this
      study. The aims were to evaluate psychological distress and pain in patients with
      advanced cancer and the impact of pain severity and pain interference dimensions
      on the anxiety and depression. One hundred twenty patients with advanced cancer
      were surveyed at a palliative care unit in Athens, Greece. Greek versions of the
      Hospital Anxiety and Depression (G-HAD) scale and the Brief Pain Inventory were
      administered. Information concerning patients' treatment received was acquired
      from the medical records, whereas physicians recorded their clinical condition.
      The analysis showed that significant associations were found between pain
      interference to "mood" and HAD-A (anxiety) (r = 0.252, P = .005) and between pain
      interference to "relations with other people" and HAD-A (r = 0.474, P < .0005).
      Multiple regression analyses showed that "average pain" (P < .05), pain
      interference to "walking ability" (P < .05), "normal work" (P < .05, and
      "relations with other people" are significant predictors of HAD-anxiety (HAD-A)
      (P < .0005), explaining 46.2% of total variance. For depression (HAD-D), the
      Greek version of the Brief Pain Inventory dimension that serve as predictor is
      "enjoyment of life," as well as the demographic variables of "age," and "gender"
      (P < .05), explaining 22.2% of variance. Moreover, a further analysis of the pain
      severity and pain interference scales showed that they differentiate the anxiety
      of the patients with cancer. In this patient sample, pain interference and, to a
      lesser extent, pain severity was significantly associated with psychological
      distress (anxiety and pain), whereas pain interference to "walking ability,"
      "normal work," and "relations with other people" was found to be more prominent
      and troublesome to patients' anxiety than that to patients' depression.

PMID- 17006116
TI  - Experiences of onset and diagnosis of low-grade glioma from the patient's
      perspective.
AB  - The aim of this study was to describe adult patients' experiences of falling ill
      and being diagnosed with low-grade glioma. Information concerning such
      experiences is lacking in the literature. The study population were adults
      identified within a well-defined population. Interviews were conducted with 27
      patients. The interview texts were analyzed using inductive content analysis.
      Illness onset was described as a sequence of events. Nineteen patients narrated
      rapid onset and 8 patients prolonged onset. The most commonly described symptoms
      in both types of onset were headache, epileptic seizures, vomiting, and vision
      changes. Racing thoughts, depression, and tinnitus were 3 of the more uncommon
      symptoms. The most prominent negative experiences regarding healthcare included
      disrespectful encounters and a lack of opportunity for participation. The salient
      negative life-situation consequences included a lack of social support and
      attitudes expressing a lack of understanding. However, to some extent, positive
      experiences also emerged in the interviews concerning healthcare and life
      situation despite the onset of the illness. In conclusion, most of the patients
      in the study experienced the illness onset as stressful. Healthcare staff need
      particular knowledge to understand the vulnerability of the patient in the onset
      of low-grade glioma.

PMID- 17006117
TI  - A pilot study of chlorhexidine and benzydamine oral rinses for the prevention and
      treatment of irradiation mucositis in patients with head and neck cancer.
AB  - This pilot study was designed to compare the efficacy of 0.2% wt/vol
      chlorhexidine gluconate and 0.15% wt/vol benzydamine hydrochloride oral rinses in
      alleviating irradiation oropharyngeal mucositis for patients with head and neck
      cancer. This was a prospective, randomized, and double-blinded study. Fourteen
      subjects were stratified based on nasopharyngeal cancer and non-nasopharyngeal
      head and neck cancer, and were randomly assigned to receive oral care protocol
      either containing with chlorhexidine (n = 7) or benzydamine (n = 7) from the
      first day to 2 weeks after the completion of radiotherapy. Subjects were
      evaluated twice weekly through days 1 to 64 using the World Health Organization
      mucositis scale and the 10 cm visual analogue scale for mouth pain and dysphagia.
      In the chlorhexidine arm, 4 subjects (57%) had grade 2, and 3 subjects (43%) had
      grade 3 mucositis. In the benzydamine arm, 5 subjects (71%) had grade 2, and 2
      subjects (29%) had grade 3 mucositis (P > .05). The mean area-under-the-curve
      values of mucositis were 26.5 +/- 13.6 (median 26) and 24.1 +/- 6.1 (median 22)
      in the chlorhexidine group and benzydamine group, respectively (P > .05). The
      mean area-under-the-curve values of pain and dysphagia were 70.8 +/- 33 (median
      88.5) and 71.5 +/- 39 (median 101), and 62.1 +/- 17.2 (median 72) and 66 +/- 22.3
      (median 57.5) in the chlorhexidine and benzydamine groups, respectively (P >
      .05). A trend has emerged of a lessening of severity of mucositis, pain, and
      dysphagia for patients with head and neck cancer receiving benzydamine oral
      rinse. The beneficial effects, however, need to be confirmed in a larger trial.

PMID- 17006118
TI  - Identification of patients with childhood moyamoya diseases showing temporary
      hypertension after anesthesia by preoperative multifractal Hurst analysis of
      heart rate variability.
AB  - OBJECTIVE: This study was performed to determine whether the preoperative
      multifractal Hurst analysis of heart rate variability might identify and
      characterize childhood patients with moyamoya disease (MMD) who showed temporary
      postoperative hypertension. METHODS: We studied 59 childhood patients with MMD.
      Thirty were classified as hypertensive group when the mean arterial pressure in
      the postoperative recovery room was 120% or greater than that during the
      preoperative period and 29 were classified as normotensive group. The 2 groups
      were compared with respect to preoperative indices of heart rate variability
      including frequency-domain measures, approximate entropy, and very short-term
      multifractal Hurst exponents of RR intervals (RRI). Using preoperative indices
      that showed significant differences, discriminant analysis was performed to
      identify postoperative hypertensive patients. RESULTS: Only exponents of the
      order > or =3 (H3alpha, H4alpha, and H5alpha) were significantly lower in the
      hypertensive group than in the normotensive group. Frequency-domain measures,
      approximate entropy, and the exponents of the order < or =2 were not
      significantly different in the 2 groups. Discriminant analysis using all of the
      three exponents correctly identified 27/30 (90%) of the postoperative
      hypertensive patients. CONCLUSIONS: Preoperative very short-term multifractal
      Hurst analysis of RRI variability identified 90% of childhood MMD patients who
      developed postoperative hypertension. The preoperative characteristic of RRI
      variability was the reduced smoothness at the 8-second-long, local RRI regions
      within which a very large change of RRI occurs.

PMID- 17006119
TI  - A comparative study between the effects of 4% endotracheal tube cuff lignocaine
      and 1.5 mg/kg intravenous lignocaine on coughing and hemodynamics during
      extubation in neurosurgical patients: a randomized controlled double-blind trial.
AB  - A prospective, randomized double-blind trial was performed to compare the effects
      of 4% endotracheal tube cuff lignocaine and 1.5 mg/kg intravenous (IV) lignocaine
      on coughing and hemodynamics during extubation in patients undergoing elective
      craniotomies in supine position. Forty-one patients received 4% lignocaine into
      the endotracheal tube cuff after intubation (ETT group) and 41 patients received
      IV lignocaine at 1.5 mg/kg before extubation (IV group). Coughing was assessed by
      a scale of 3 at the time of extubation. Hemodynamic parameters recorded at 1
      minute interval after extubation for 5 minutes were compared with the baseline
      values recorded before skin closure. Results showed that there was no significant
      difference between the groups in terms of coughing or the hemodynamic response to
      tracheal extubation. In conclusion, 4% endotracheal tube cuff lignocaine was not
      superior to 1.5 mg/kg IV lignocaine in attenuating coughing and hemodynamic
      changes during extubation.

PMID- 17006120
TI  - Assessing risk factors for postoperative nausea and vomiting: a retrospective
      study in patients undergoing retromastoid craniectomy with microvascular
      decompression of cranial nerves.
AB  - We have observed that patients, after retromastoid craniectomy (RMC) with
      microvascular decompression (MVD) of cranial nerves, frequently experienced
      postoperative nausea and vomiting (PONV). The authors conducted this study to
      track the incidence of PONV and to identify potential factors for PONV after RMC
      with MVD. Medical records from 185 adults, who underwent elective RMC with MVD,
      were identified and reviewed from January 2000 to December 2004. Extracted data
      included patient, anesthesia, and surgery related variables that were considered
      to have a possible effect on the patients experiencing PONV after RMC with MVD.
      Despite the use of intraoperative prophylactic ondansetron in 99% of patients,
      the overall incidence of PONV (nausea or emesis or both) was 60% during the first
      24 hours postoperatively. It was higher for the patients after RMC with MVD of
      cranial nerve V [69%, 82/119, P=0.005, odds ratio (OR)=2.8]. Regression modeling
      demonstrated that female sex (OR=3.0, P=0.005) and use of desflurane (OR=2.8,
      P=0.003) were significant independent predictors of PONV. Prophylactic
      transdermal scopolamine patch administered preoperatively was associated with
      less PONV (OR=0.3, P=0.001). We concluded that PONV occurs frequently in adults
      recovering from RMC with MVD. The results of this study suggest that it may be
      necessary to administer a combination of antiemetics to decrease the incidence of
      PONV after RMC.

PMID- 17006121
TI  - NMDA-induced apoptosis in mixed neuronal/glial cortical cell cultures: the
      effects of isoflurane and dizocilpine.
AB  - In animal models of severe ischemia, it has not been uniformly observed that
      anesthetics are protective. However, anesthetics have not been evaluated in the
      presence of a mild excitotoxic insult. We hypothesized that in the presence of a
      mild excitotoxic insult, 3 microm N-methyl-D-aspartate (NMDA), isoflurane may
      prevent apoptotic cell death. Primary mixed neuronal/glial cultures were prepared
      from fetal rat brains. Mature cultures were exposed to dissolved isoflurane [0
      mM, 0.4 mM (1.8 minimum alveolar concentration) or 1.6 mM (7 minimum alveolar
      concentration)] or dizocilpine (10 microM), and NMDA (0 or 3 microM) at 37
      degrees C for 30 minutes. Apoptosis was assessed using terminal-deoxy-nucleotidyl
      end-nick labeling oligonucleosomal DNA fragmentation enzyme-linked immunosorbent
      assay, and caspases-3 and -9 activation assays. NMDA (3 muM) induced apoptosis in
      mixed neuronal/glial cell cultures. Apoptosis induced by 3 microm NMDA was
      caspase-3 but not caspase-9 mediated. In the presence of a mild excitotoxic
      insult, this investigation showed an attenuation of apoptotic cell death by
      dizocilpine, but not isoflurane.

PMID- 17006122
TI  - Description and first clinical application of AirWay Scope for tracheal
      intubation.
AB  - We have developed a novel airway apparatus, AirWay Scope, which we have used in
      the orotracheal intubation of 10 consecutive patients requiring general
      anesthesia before neurosurgical procedures. The characteristic shape of the
      introducer (INTLOCK), the tube guiding function and the sighting device of the
      AirWay Scope has possibility to facilitate tracheal intubation. Here, we report
      the first clinical application of this system and describe potential advantages
      of the apparatus.

PMID- 17006123
TI  - An audit of fluid and heparin administration during interventional
      neuroradiologic procedures.
AB  - Vascular lesions of the brain such as aneurysms and arteriovenous malformations
      are increasingly being treated by radiologists. They use heparinized saline in
      pressurized bags to flush the catheter systems continuously. This fluid could
      have detrimental effects if the volume infused is high. Therefore, we measured
      the amount of heparinized saline used by radiologists and tried to assess its
      significance. Data were collected from the first 50 patients who underwent
      interventional treatment during September to December 2004. Fluid and heparin,
      administered by both the radiologists and anesthesiologists, were recorded in
      addition to demographics and postoperative complications. The mean age of
      patients was 49+/-14 years. The average volume of fluid given by the radiologists
      was 980+/-480 mL. The anesthesiologists administered an average of 1500 mL
      crystalloids and 650 mL of colloids. The overall fluid balance at the end of
      procedure was positive by 2122+/-947 mL. The amount of heparin administered by
      flush solution was a mean of 2500+/-1200 IU. The total amount of fluid
      administered had no relation to the development of vasospasm or infection.
      However, a statistically nonsignificant (P=0.15) 30% increase in total fluid
      administered to patients, who required postoperative mechanical ventilation,
      suggests that the relationship between fluid administration and postoperative
      mechanical ventilation should be investigated further in patients who undergo
      interventional neuroendovasular procedures. In conclusion, radiologists
      administer significant amount of fluid and heparin during interventional
      procedures. Routine recording and monitoring of all fluid and heparin
      administered is advisable in interventional neuroendovasular procedures. The
      relationship between fluid administration and postoperative mechanical
      ventilation should be investigated further in patients who undergo interventional
      neuroendovasular procedures.

PMID- 17006124
TI  - A comparative study between preoperative and postoperative pulmonary functions
      and diaphragmatic movements in congenital craniovertebral junction anomalies.
AB  - Respiratory dysfunctions in patients with craniovertebral junction (CVJ)
      anomalies may occur due to compression of brainstem affecting the respiratory
      centers, and weakening of the muscles of respiration. We assessed pulmonary
      functions [forced vital capacity (FVC), forced expiratory volume in first second
      (FEV1), maximum mid-expiratory flow rate (FEF25%-75%), FEV1%], mouth pressures
      (maximum inspiratory pressure, maximum expiratory pressure), and diaphragmatic
      movements in 30 patients of CVJ anomalies and compared them with their mean
      predictive values. These parameters were also assessed in the postoperative
      period. It was found that the mean values of FVC, FEV1, and FEF25%-75% were
      significantly lower (P<0.001) than their mean predictive values (2.4+/-0.8 L,
      2.0+/-0.7 L, 2.5+/-0.9 L vs. 3.7+/-0.9 L, 3.2+/-0.7 L, and 3.4+/-0.7 L,
      respectively). In the postoperative period there was significant reduction
      (P<0.05) in all these parameters (2.2+/-0.8 L, 1.7+/-0.7 L, and 2.1+/-0.8 L,
      respectively). The postoperative FEV1% was 78.8% compared with the preoperative
      value of 85.7%. A restrictive pattern of lung disease was observed which
      persisted in the postoperative period. The postoperative maximum inspiratory
      pressure and maximum expiratory pressure were comparable to their preoperative
      values (47.9+/-19.6 and 47.0+/-16.7 cmH2O vs. 42.6+/-17.3 and 43.9+/-18.2 cmH2O,
      respectively). Similarly, the diaphragmatic movements were also comparable to the
      preoperative values, both during quiet and deep breathing (13.7+/-3.9 and 38.0+/
      9.3 mm vs. 13.8+/-3.9 and 39.0+/-9.1 mm, respectively). There was no improvement
      of pulmonary functions in the early postoperative period. However, a long-term
      follow-up is needed to determine subsequent changes of these parameters.

PMID- 17006128
TI  - Does nitrous oxide affect bispectral index in patients under isoflurane
      anesthesia?

PMID- 17006129
TI  - United Kingdom and Ireland survey of the use of nonsteroidal anti-inflammatory
      drugs after intracranial surgery.

PMID- 17006130
TI  - Flush test--a new technique to assess the malposition of subclavian central
      venous catheter position in the internal jugular vein.

PMID- 17006258
TI  - A call to action: Cancer in adolescents and young adults: An unrecognized
      healthcare disparity.

PMID- 17006259
TI  - No Influence of bcl-2, p53, and p21waf1 protein expression on the outcome of
      pediatric Hodgkin lymphomas.
AB  - In Argentina, lymphomas account for 13.6% of all pediatric tumors and 47% of them
      are Hodgkin lymphoma. Previous studies of lymphoma series have reported the
      expression of apoptotic and cell cycle proteins. Our aim was to study these
      markers in our pediatric patients and correlate them with their outcome.
      Immunohistochemical staining with monoclonal antibodies anti-p53, bcl-2, p21, and
      mdm2 were performed on formalin-fixed paraffin-embedded Hodgkin lymphoma lymph
      node biopsies from 54 pediatric patients. The analyzed oncogenes p53, bcl-2, p21,
      and mdm2 exhibited 81%, 44%, 76%, and 90% positive staining, respectively. The
      most prevalent p53/p21 expression pattern was p53+/p21+, in 57% of cases, whereas
      concerning p53/mdm2 expression pattern p53+/mdm2+ was observed in 61% of cases.
      We failed to find any statistically significant correlation between oncogene
      expression and patient's survival. It seems that p53 plays an important role in
      lymphomagenesis in our studied population, because it is overexpressed in 81% of
      Hodgkin lymphoma cases and in more than 50% of cases, it might be able to
      activate its cellular effectors. Bcl-2 staining observed in 44% of our cases
      could represent a failure in bcl-2 down-regulation that leads to a rescue event
      in defective germinal center B-cells, that allows them to develop into Reed
      Sternberg and Hodgkin cells.

PMID- 17006260
TI  - Nutritional megaloblastic anemia in young Turkish children is associated with
      vitamin B-12 deficiency and psychomotor retardation.
AB  - We aimed to investigate the presence of psychomotor retardation, physical and
      laboratory examination in infants with megaloblastic anemia. Inclusion criteria
      for the study were; age 9 to 36 months, refusal of food except for breast and cow
      milk, loss of appetite, developmental delay, significant pallor, and
      hypersegmentation neutrophils in the peripheral blood smear. A total of 33
      children fulfilling the inclusion criteria were enrolled among 3368 patients
      attending Pediatric Outpatient Clinics of sirnak-Cizre State Hospital between
      January 25, 2004 and May 5, 2004. Mean age was 16.4 months. Thirty-two patients
      had Vitamin B12 deficiency, 1 patient had folate deficiency, and 10 patients had
      combined vitamin B12 and folate deficiency. Statistically, a positive significant
      relationship was detected between serum vitamin B12 levels and mean corpuscular
      volume (P = 0.001, r = 0.56), and between vitamin B12 levels and hemoglobin (P =
      0.004, r = 0.49). We believe that preventative measures such as fortification of
      flour with vitamin B12, nutritional support with vitamin B12 for the mother
      during pregnancy and nursing, provision of adequate primary preventive health
      services, and starting complementary food after 6 months of age are important
      determinants for preventing megaloblastic anemia.

PMID- 17006261
TI  - Significance of persistent mature rhabdomyoblasts in bladder/prostate
      rhabdomyosarcoma: Results from IRS IV.
AB  - Terminally differentiated rhabdomyoblasts are common after or during therapy for
      rhabdomyosarcoma (RMS). Case reports have suggested that their presence after
      therapy does not indicate a poor prognosis, but significance and relationship to
      outcome has not been systematically studied. Management of patients with this
      finding can cause confusion. Slides and pathology reports from 44 patients with
      bladder/prostate RMS treated on Fourth Intergroup Rhabdomyosarcoma Study were
      examined by a pathologist experienced in RMS, and findings compared with
      institutional reports. Details regarding patient characteristics, outcome, and
      management were reviewed. Outcome of patients with various pathologic findings
      was assessed. One of 10 patients with only mature rhabdomyoblasts at their last
      procedure recurred, versus 4 of 17 patients with viable tumor and 2 of 17
      patients with no viable tumor and no rhabdomyoblasts. Sixteen of 42 cases
      reviewed had results differing from our review. Mature rhabdomyoblasts are a
      discrete entity which may not be predictive of recurrence, but should be
      evaluated by a pathologist experienced with this entity. The presence of mature
      rhabdomyoblasts at the end of therapy for bladder/prostate RMS does not justify
      radical surgery. Sequential biopsies are subject to sampling error and should
      only be performed in the context of protocol-directed therapy to avoid
      unnecessary radical surgeries.

PMID- 17006262
TI  - Mature B-cell lymphoma in children and adolescents: International group
      pathologist consensus correlates with histology technical quality.
AB  - In pediatric mature B-cell non-Hodgkin lymphoma, international pathologist
      diagnostic agreement was previously evaluated using the Revised European-American
      Lymphoma Classification. Surgical biopsy histology technical quality (HTQ) is
      variable and may affect diagnostic accuracy. This study evaluated diagnostic
      agreement correlated with HTQ. Surgical biopsies obtained from international
      protocol FAB LMB96 Treatment of Mature B-Cell Lymphoma/Leukemia for Burkitt
      lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and high-grade B-cell
      lymphoma Burkitt-like (BLL), were independently reviewed by hematopathologists
      from 3 national groups (Children's Cancer Group, Societe Francaise d'Oncologie
      Pediatrique, and United Kingdom Children's Cancer Study Group) to determine each
      national diagnosis and a final diagnosis. HTQ grades for microscopic tissue
      sections included: good; medium; low; inconclusive. Final diagnoses in 187 cases
      included: BL 87 (47%); BLL 20 (11%); DLBCL 64 (34%); other 16 (9%). HTQ grades
      included: good 10 (5%); medium 100 (54%); low 75 (40%); inconclusive 2 (1%). The
      rate of uniform agreement between the national diagnoses was significantly higher
      with good or medium HTQ (62%) than with low HTQ (33%) (P = 0.001). In conclusion,
      in pediatric mature B-cell non-Hodgkin lymphoma, international pathologist
      diagnostic agreement is significantly higher in surgical biopsies with better
      HTQ. Poor HTQ may adversely impact diagnostic ability and affect prognosis and
      therapeutic management when different treatment regimens are employed for DLBCL
      versus BL/BLL.

PMID- 17006264
TI  - Can renal leukemic infiltration cause hypertension in children?
AB  - Out of 334 children with acute lymphoblastic leukemia who were treated with St
      Jude Total XI and Total XIII chemotherapy protocols were investigated and 21
      (6.3%) were hypertensive. The incidence of tumor lysis syndrome was higher in the
      hypertensive group than in the nonhypertensive group (28.6% vs. 11.5%) (P =
      0.035). There were no differences between patients treated with high-dose
      methylprednisolone and prednisolone St Jude Total XI and Total XIII, St Jude
      Total XIII LR and St Jude Total XIII HR groups in respect of the above-mentioned
      parameters. Central nervous system involvement, skeletal system involvement,
      abdominal lymphadenopathy, elevated lactate dehydrogenase and leukocyte count,
      French-American-British types and immunophenotypes were not found to be
      statistically significant to the development of hypertension (P > 0.05). We found
      that renal leukemic infiltration is a risk factor in hypertension development (P
      = 0.04) and hypertension is a risk factor for renal parenchymal disorder in the
      follow-up period (P = 0.0001). Six patients presenting with hypertension in the
      first week of disease therapy were evaluated for renal parenchymal disorder and
      glomerular filtration rate abnormality in the follow-up period. Glomerular
      filtration rate abnormality was found in 1 and renal scintigraphic
      dimercaptosuccinic acid abnormalities (reduced uptake and dilated hypoactivity)
      were found in 4 patients. Hypertension was also found to be a risk factor for
      renal parenchymal disorder in the follow-up period.

PMID- 17006263
TI  - Obesity and survival in a cohort of predominantly Hispanic children with acute
      lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL), the most common malignancy in children,
      constitutes 25% of all pediatric cancer. Childhood cancer patients who are obese
      at diagnosis represent a particular challenge for the oncologist. Obesity may
      complicate chemotherapy dose determination, and has been associated with
      decreased overall and event-free survival in a number of adult cancer patients,
      and more recently in pediatric patients. The purpose of the present study was to
      examine whether obesity at diagnosis was associated with decreased overall and
      event-free survival in a cohort of 322 predominantly Hispanic pediatric patients
      with B-precursor ALL. Obesity was classified as an age-standardized and sex
      standardized body mass index z-score at or above the 95th percentile. Hazard
      ratios (HRs) for overall and event-free survival were assessed using Cox
      proportional hazards regression modeling. Obesity at diagnosis was not associated
      with decreased overall survival (HR = 1.40, 95% confidence interval = 0.69-2.87)
      or event-free survival (HR = 1.08, 95% confidence interval = 0.65-1.82) in the
      overall cohort or in either of the 2 age-at-diagnosis (2 to 9 y; 10 to 18 y)
      subgroups. Our finding of no obesity-related prognostic effect in the overall
      cohort and in the under 2 to 9-year age-at-diagnosis cohort was consistent with
      the previous large-scale study of ALL patients; the absence of a prognostic
      effect in the 10 to 18-year age-at-diagnosis cohort, however, conflicted with
      previous findings.

PMID- 17006265
TI  - Rituximab (anti-CD20) adjunctive therapy for opsoclonus-myoclonus syndrome.
AB  - PURPOSE: To determine if rituximab, an anti-CD20 monoclonal antibody, reduces
      cerebrospinal fluid (CSF) B-cell expansion in opsoclonus-myoclonus syndrome (OMS)
      and results in clinical improvement. METHODS: Sixteen children with OMS and
      increased % CD20 B-cells in CSF received 4 rituximab infusions (375 mg/m IV) as
      add-on therapy to corticotropin (ACTH), intravenous immunoglobulins, or both, and
      were reevaluated 6 months later. Outcome measures were clinical (motor function,
      behavior, sleep) and immunologic (CSF and blood immunophenotype and Ig levels).
      Controls were 16 age-matched and sex-matched children, who did not have OMS.
      RESULTS: After rituximab, 81% of OMS had a lower motor severity score, and 44%
      improved one severity category. Mean total score decreased by 44% (P = 0.0005).
      Rituximab reduced rage score, nighttime awakenings, and the number of children
      with opsoclonus, action myoclonus, drooling, gait ataxia, and rage. Despite a 51%
      reduction in ACTH dose, 9 of 11 children on ACTH did not relapse. The percentage
      of CSF CD19 (and CD20) B-cells was lowered in all children (undetectable in 6),
      with a 90% reduction in the group mean (P = 0.00003). CSF B-cells were no longer
      expanded compared with controls. In blood, CD19 B-cells decreased (-90%, P =
      0.0003), as did the CSF:blood CD19 B-cell ratio (P = 0.00003). Serum IgM fell by
      69% (below reference range), with no statistically significant change in IgG or
      IgA. CONCLUSIONS: Rituximab seems efficacious and safe as adjunctive therapy for
      OMS. Selective targeting of CSF B lymphocytes represents a novel and valuable
      paradigm shift in the therapy for centrally mediated paraneoplastic disorders.

PMID- 17006266
TI  - A thoracic wall lipoblastoma in a 3-month-old infant: A case report and review of
      the literature.
AB  - Lipoblastoma is a rare benign tumor of adipose tissue seen almost always in
      infancy and early childhood. Lipoblastoma is present in 2 forms which are
      pathologically identical: circumscribed and diffuse. It is typically located in
      the extremities, and less frequently in head-neck region, trunk, and various
      organs. Lipoblastoma is a tumor with good prognosis with no reported metastases,
      despite its potential for local invasion and rapid growth. Our patient was a 3
      month-old boy who was brought to our clinic for rapidly growing mass in the right
      hemithorax. With the aim of both diagnosis and treatment, the lipomatous mass was
      removed by local resection. In addition to the patient's age, histologic and
      cytogenetic analyses assisted the diagnosis of diffuse lipoblastoma. In the
      postoperative period, the thorax wall was unaffected, and after 6 years of follow
      up no recurrence was observed. In the English literature, 8 cases of thoracic
      wall lipoblastoma have been previously reported, and only 3 of diffuse form.
      Here, we report, at our knowledge, the fourth case of thoracic diffuse
      lipoblastoma, in which cytogenetic analysis showed a previously undescribed
      karyotype aberration involving chromosomes 8, 13, and 16.

PMID- 17006267
TI  - Evidence for symptom management in the child with cancer.
AB  - The use of complementary/alternative medicine (CAM) has been well documented
      among children with cancer. This report summarizes the research evidence on the
      role of CAM therapies for prevention and treatment of the most commonly reported
      cancer-related symptoms and late effects among children with cancer. Small
      clinical trials document evidence of effectiveness for select therapies, such as
      acupuncture or ginger for nausea and vomiting, TRAUMEEL S for mucositis, and
      hypnosis and imagery for pain and anxiety. Several relatively small clinical
      trials of varying quality have been conducted on these CAM therapies in children
      with cancer. Some herbs have demonstrated efficacy in adults, but few studies of
      herbs have been conducted in children. Larger randomized clinical trials are
      warranted for each of these promising therapies. Until the evidence is more
      conclusive, the providers' role is to assess and document the child's use of CAM,
      critically evaluate the evidence or lack of evidence, balance the potential risks
      with possible benefits, and assist the family in their choices and decisions
      regarding use of CAM for their child with cancer.

PMID- 17006268
TI  - Fanconi anemia patient with bilaterally hypoplastic scapula and unilateral
      winging associated with scoliosis and rib abnormality.
AB  - Fanconi anemia is an autosomal recessive disease characterized by bone marrow
      failure, variable congenital physical abnormalities, and predisposition to
      hematologic malignancy and several solid tumors. The most frequently associated
      congenital malformations are those of the skeletal system, mainly radius and
      thumb. Herein, we report bilaterally hypoplastic scapula with unilateral winging
      associated with scoliosis and rib abnormality, a previously unreported skeletal
      abnormality in Fanconi anemia patients.

PMID- 17006269
TI  - Bilateral renal metastases from osteosarcoma: A case report and review of the
      literature.
AB  - Improvements in multimodal therapy for osteosarcoma (OS) have increased event
      free and overall survival. But have also led to a greater number of recurrences
      in uncommon sites. We report a young adult with OS who developed late bilateral
      renal relapse. Late recurrences to the kidneys have a more aggressive clinical
      behavior and poor prognosis documented by 15 cases of OS metastastic to the
      kidney in the literature. Two of those patients had a long survival after
      chemotherapy and surgery. This suggests that the disease can be controlled with
      early detection and treatment.

PMID- 17006270
TI  - Epstein-Barr virus associated Hodgkin lymphoma in a 9-year-old girl receiving
      long-term methotrexate therapy for juvenile idiopathic arthritis.
AB  - We describe a case of Hodgkin lymphoma developing in a 9-year-old girl with
      polyarticular, rheumatoid factor-positive juvenile idiopathic arthritis treated
      with methotrexate (MTX), prednisone, and naproxen for 5 years. Pathologic and
      molecular analyses revealed that the Hodgkin cells contained Epstein-Barr virus
      and the viral DNA was monoclonal. She achieved complete remission after MTX
      withdrawal, chemotherapy, and radiation. To the best of my knowledge, this is the
      sixth report of Hodgkin lymphoma in patients with juvenile idiopathic arthritis
      receiving low dose MTX therapy.

PMID- 17006271
TI  - Growth hormone deficiency after localized ganglioneuroblastoma: A case report.
AB  - Growth hormone deficiency (GHD) related to standard dose chemotherapy has rarely
      been described. We report on a case of localized ganglioneuroblastoma treated by
      carboplatin/etoposide for 2 courses and surgery, which developed a serious GHD
      after 56 months. At present, the child is growing on by GH replacement therapy.
      We discuss about the hypothesis that GHD may be related to chemotherapy and we
      report a review of previous published cases.

PMID- 17006272
TI  - Failure of viridans group streptococci causing bacteremia in pediatric oncology
      patients to express superantigens.
AB  - Group A Streptococcus pyogenes causes a distinctive clinical disorder,
      streptococcal toxic shock syndrome, mediated by superantigenic bacterial
      exotoxins. Oncology patients with viridans group streptococcal sepsis frequently
      present with a streptococcal toxic shocklike syndrome of unclear pathogenesis.
      Viridans group streptococci isolated from pediatric oncology patients with
      streptococcal toxic shocklike illnesses do not possess homologs of known
      superantigen genes. Supernatants from cultures of these bacteria also fail to
      stimulate T-cell proliferation, suggesting these bacteria do not commonly
      elaborate superantigens. Adjunctive treatment with intravenous immunoglobulin,
      which is advantageous in streptococcal toxic shock syndrome, may not benefit
      these patients.

PMID- 17006273
TI  - Recurrent life-threatening hemothorax in an infant with pleurocutaneous
      kaposiform hemangio-endothelioma.

PMID- 17006274
TI  - Pediatric stroke, homocysteine and MTHFR 677C-T and 1298 A-C.

PMID- 17006275
TI  - Acute lymphoblastic leukemia with massive myelofibrosis.

PMID- 17006276
TI  - Skeletal hemangiomas and vascular malformations.

PMID- 17006277
TI  - The Pediatric Infectious Diseases Society annual awards, 2006.

PMID- 17006279
TI  - Superior relative efficacy of live attenuated influenza vaccine compared with
      inactivated influenza vaccine in young children with recurrent respiratory tract
      infections.
AB  - BACKGROUND: Young children have a high incidence of influenza and influenza
      related complications. This study compared the efficacy and safety of cold
      adapted influenza vaccine, trivalent (CAIV-T) with trivalent inactivated
      influenza vaccine (TIV) in young children with a history of recurrent respiratory
      tract infections (RTIs). METHODS: Children 6 to 71 months of age were randomized
      to receive 2 doses of CAIV-T (n = 1101) or TIV (n = 1086), 35 +/- 7 days apart
      before the start of the 2002-2003 influenza season and were followed up for
      culture-confirmed influenza, effectiveness outcomes, reactogenicity, and adverse
      events. RESULTS: Overall, 52.7% (95% confidence interval [CI] = 21.6%-72.2%)
      fewer cases of influenza caused by virus strains antigenically similar to vaccine
      were observed in CAIV-T than in TIV recipients. Greater relative efficacy for
      CAIV-T was observed for the antigenically similar A/H1N1 (100.0%; 95% CI = 42.3%
      100.0%) and B (68.0%; 95% CI = 37.3%-84.8%) strains but not for the antigenically
      similar A/H3N2 strains (-97.1%; 95% CI = -540.2% to 31.5%). Relative to TIV, CAIV
      T reduced the number of RTI-related healthcare provider visits by 8.9% (90% CI =
      1.5%-15.8%) and missed days of school, kindergarten, or day care by 16.2% (90% CI
      = 10.4%-21.6%). Rhinitis and rhinorrhea, otitis media, and decreased appetite
      were the only events that were reported more frequently in CAIV-T subjects. There
      was no difference between groups in the incidence of wheezing after vaccination.
      CONCLUSIONS: CAIV-T was well tolerated in these children with RTIs and
      demonstrated superior relative efficacy compared with TIV in preventing influenza
      illness.

PMID- 17006280
TI  - Persistence of erythromycin-resistant group a streptococci in cultured
      respiratory cells.
AB  - BACKGROUND: A significant association between erythromycin resistance and ability
      of bacteria to enter human respiratory cells has been documented in group A
      streptococci (GAS) isolated in Italy from children with pharyngitis. The
      occurrence of strains combining cell invasiveness with erythromycin resistance
      raised serious concern because they could escape penicillin by virtue of
      intracellular location and macrolides by virtue of resistance, resulting in
      difficulty in eradication. METHODS: Thirty-one pharyngeal cell-invasive,
      erythromycin-resistant (ER) GAS, representing that many clones recently
      identified among Italian GAS carrying the internalization-related gene prtF1,
      were investigated for intracellular persistence inside cultured respiratory cells
      (A549) by means of a survival assay and by staining and polymerase chain reaction
      assays on infected cells. RESULTS: All tested ER GAS could be recovered in
      culture from infected cells 24 hours from infection with logarithms exceeding 4.0
      (4 strains). The highest survival rate (>5.0) was exhibited by strain SP1900
      [erm(A)/iMLS-B; high-level erythromycin resistance [minimum inhibitory
      concentration, > or =128 microg/mL)], the most widespread clone, which was
      cultivable from infected cells up to day 5. As long as SP1900-infected cells
      could be maintained in culture, the presence of multiple cocci inside cells was
      consistently revealed by microscopy. During the same time, DNA sequences internal
      to both genes prtF1 and erm(A) continued to be amplified by polymerase chain
      reaction. CONCLUSIONS: These results suggest that the ER GAS are capable of
      persisting in human respiratory cells. This might contribute to clinical problems
      such as relapsing infection and persistent carriage despite antibiotic treatment
      and might have facilitated the widespread diffusion of ER GAS in Italy.

PMID- 17006278
TI  - Comparison of the efficacy and safety of live attenuated cold-adapted influenza
      vaccine, trivalent, with trivalent inactivated influenza virus vaccine in
      children and adolescents with asthma.
AB  - BACKGROUND: Despite their potential for increased morbidity, 75% to 90% of
      asthmatic children do not receive influenza vaccination. Live attenuated
      influenza vaccine (LAIV), a cold-adapted, temperature-sensitive, trivalent
      influenza vaccine, is approved for prevention of influenza in healthy children 5
      to 19 years of age. LAIV has been studied in only a small number of children with
      asthma. METHODS: Children 6 to 17 years of age, with a clinical diagnosis of
      asthma, received a single dose of either intranasal CAIV-T (an investigational
      refrigerator-stable formulation of LAIV; n = 1114) or injectable trivalent
      inactivated influenza vaccine (TIV; n = 1115) in this randomized, open-label
      study during the 2002-2003 influenza season. Participants were followed up for
      culture-confirmed influenza illness, respiratory outcome, and safety. RESULTS:
      The incidence of community-acquired culture-confirmed influenza illness was 4.1%
      (CAIV-T) versus 6.2% (TIV), demonstrating a significantly greater relative
      efficacy of CAIV-T versus TIV of 34.7% (90% confidence interval [CI] 9.4%-53.2%;
      95% CI = 3.9%-56.0%). There were no significant differences between treatment
      groups in the incidence of asthma exacerbations, mean peak expiratory flow rate
      findings, asthma symptom scores, or nighttime awakening scores. The incidence of
      runny nose/nasal congestion was higher for CAIV-T (66.2%) than TIV (52.5%)
      recipients. Approximately 70% of TIV recipients reported injection site
      reactions. CONCLUSIONS: CAIV-T was well tolerated in children and adolescents
      with asthma. There was no evidence of a significant increase in adverse pulmonary
      outcomes for CAIV-T compared with TIV. CAIV-T had a significantly greater
      relative efficacy of 35% compared with TIV in this high-risk population.

PMID- 17006281
TI  - Hypothesis: Neonatal respiratory distress may be related to asymptomatic
      colonization with group B streptococci.
AB  - BACKGROUND: Phospholipids from the group B streptococcal (GBS) cell wall cause
      pulmonary hypertension in experimental animals. When exposed to penicillin,
      Streptococcus mutans releases phospholipids immediately. We hypothesize that
      newborns colonized with GBS receive bacterial phospholipids leading to pulmonary
      hypertension and respiratory distress, especially in the situation of newborns of
      penicillin-treated mothers. We examined clinical and epidemiologic data on these
      relations. METHODS: We used data from a prospective multicenter GBS study
      conducted from 1995 to 1999 in which 1674 of 17,690 newborns cultured at 4 sites
      were colonized with GBS. Our analyses included 1610 colonized newborns > or =32
      weeks gestation without early-onset disease. Clinical features were compared
      between 1003 lightly colonized (GBS positive at < or =2 sites) and 607 heavily
      colonized (positive at 3 or 4 sites) newborns. The rates of respiratory distress
      were compared between colonized newborns of penicillin-treated mothers and those
      of untreated mothers. RESULTS: Of the 1610 colonized newborns, 8.8% had signs of
      respiratory distress within 48 hours after birth (cases). Oxygen supplementation
      was used in 60% of the cases, mechanical ventilation was required in 5% and
      persistent pulmonary hypertension was diagnosed in 2%. Compared with light
      colonization, heavy colonization increased the rate of respiratory distress 1.73
      fold (95% CI, 1.26-2.38), a discharge diagnosis of respiratory disorder 2.02-fold
      (95% CI, 1.16-3.52), a blood/cerebrospinal fluid obtained for culture 1.54-fold
      (95% CI, 1.24-1.93) and antibiotic administration after birth 1.87-fold (95% CI,
      1.34-2.61). Penicillin use during labor was associated with a 2.62-fold (95% CI,
      1.79-3.83) increase in respiratory distress in the colonized newborn.
      CONCLUSIONS: Our findings support the association of neonatal respiratory
      distress with asymptomatic GBS colonization and with penicillin use during labor.
      These data require confirmation.

PMID- 17006282
TI  - Neonatal enterovirus infections reported to the national enterovirus surveillance
      system in the United States, 1983-2003.
AB  - BACKGROUND: Neonatal enterovirus (EV) infections lead to a wide range of clinical
      manifestations, from mild febrile illness to severe, sometimes fatal, sepsislike
      disease. METHODS: To determine the relationship of EV serotypes with the risk of
      neonatal infection and its fatal outcome, we analyzed data reported to the
      National Enterovirus Surveillance System (NESS) during 1983-2003. RESULTS: Of the
      26,737 EV detections reported during this period, neonates accounted for 2544
      (11.4% of those with known age). Serotypes most commonly isolated from neonates
      included echovirus (E) 11 (14.0% of EV with known serotype), coxsackievirus (CV)
      B2 (8.9%), CVB5 (7.5%), E6, E9 and CVB4 (6.8% each). CVB1-4, E11, and E25 were
      significantly more common, whereas CVA16, E4, E9, E21, E30, and human
      parechovirus 1 (formerly E22) were less common among neonates than among persons
      aged > or =1 month. Fatal outcome was noted for 3.3% of reports, with neonates at
      a higher risk of death than persons aged > or =1 month (11.5% versus 2.5%; odds
      ratio [OR] 5.1; 95% confidence interval [CI] = 3.3-7.8). Neonates infected with
      CVB4 were at a higher risk of death (OR 6.5; 95% CI = 2.4-17.7) than those
      infected with other EV. CONCLUSION: EV are important neonatal pathogens
      associated with high risk of infection and death. Because of the limitations of
      the NESS (incomplete reporting, limited clinical data, bias towards more severe
      and younger cases), additional studies are needed to better evaluate the role of
      different EV in neonatal infections.

PMID- 17006283
TI  - Elevated soluble thrombomodulin in the febrile stage related to patients at risk
      for dengue shock syndrome.
AB  - BACKGROUND: Children with dengue hemorrhagic fever (DHF) are at risk to develop
      dengue shock syndrome (DSS) for which neither marker has been demonstrated.
      OBJECTIVE: The study was designed to investigate the markers of vascular
      endothelial cell injuries and dysfunction that might be used as early predictors
      of the subsequent manifestation of DSS. METHODS: The blood samples from 111
      patients with dengue fever, DHF and other febrile illness (OFI) were collected
      daily from the day of admission until discharge and at convalescent stage. The
      sample from the day of defervescence was defined as day 0, 1 day before
      defervescence was defined as day -1 and so on. Also, 1 day after defervescence
      was defined as day +1 and so on. RESULTS: Increased soluble thrombomodulin (sTM)
      was demonstrated in dengue-infected patients via an enzyme-linked immunosorbent
      assay. Patients with DSS (DHF grades III and IV) had higher concentrations of sTM
      than those with dengue fever, DHF grade I, II and OFIs from day -3 until day +2.
      Increased circulating endothelial cells were detected from day 0 until day +2 in
      DSS patients as compared with other groups. In addition, increased soluble
      vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1 and
      soluble E-selectin were also found in dengue virus-infected patients as compared
      with OFIs. CONCLUSION: Blood sTM may be useful as an early predictor of DSS in
      dengue infected patients in the febrile stage. However, a further evaluation in a
      large prospective series is needed.

PMID- 17006285
TI  - Prevalence of herpes simplex virus types 1 and 2 among children and adolescents
      attending a sexual abuse clinic.
AB  - BACKGROUND: Children and adolescents with a history of sexual abuse are at risk
      for acquiring herpes simplex virus (HSV) type 2. We evaluated the prevalence of
      HSV-1 and HSV-2 and the usefulness for this population of 2 commercially
      available tests. METHODS: Sera from 150 children seen in a sexual abuse clinic
      were analyzed for type-specific HSV antibodies using Focus HerpeSelect HSV-2
      ELISA (Focus), Biokit HSV-2 Rapid Test (Biokit), and by Western blot (WB).
      RESULTS: The patient sample was 81% female, had a mean age of 11.6 years (range,
      1 to 18 years), and was 46% Caucasian, 28% Hispanic, 25% African American, and 2%
      other. According to WB, 77 (51%) of the children were HSV-1 seropositive. For HSV
      2, there was 1 "true positive" (positive by all 3 tests) and 1 patient whose
      serum had atypical HSV-2 bands by WB but was positive by Focus. There were 6 sera
      that were positive by Focus and negative by WB. Index values of these 6 Focus
      tests were not predictive of WB status. For the 105 samples for which Biokit data
      were available, all samples were concordant with WB. CONCLUSIONS: The findings of
      this study suggest that routine screening for HSV-2 in sexually abused children
      does not have a high yield. The Focus test has an unacceptably high rate of false
      positive results in children; however, Biokit may be an acceptable substitute for
      WB in evaluating children for HSV-2 antibodies.

PMID- 17006284
TI  - Acute human parvovirus B-19 infection in hospitalized children: A serologic and
      molecular survey.
AB  - BACKGROUND: The extent and clinical manifestations of acute human parvovirus B19
      (B19) infection were assessed in previously healthy hospitalized children
      admitted with clinical syndromes potentially associated the virus. PATIENTS AND
      METHODS: The study was prospective and was conducted between October 2002 and
      August 2004 in the pediatric departments of 3 hospitals in Israel. The survey
      included previously healthy children who were hospitalized with 1 or more of the
      following acute diseases: acute nonallergic exanthema, fever for >1 week,
      aplastic anemia or pancytopenia, acute nonbacterial arthropathy, immune
      thrombocytopenic purpura (ITP), Henoch-Schonlein purpura (HSP) and aseptic
      meningitis. A control group of children with a proven, non-B19 infection was also
      studied. Serum samples obtained from each child on admission were tested for B19
      DNA by real-time PCR and B19 IgM by ELISA. Acute B19 infection was defined by the
      following criteria: positive serum B19-DNA and/or B19 IgM, negative serum B19
      IgG, and no other proven infection. RESULTS: Overall, 167 children were included
      in the study. The mean age was 5.5 +/- 4.6 years (range, 0.5-17), males and
      females equally divided. Acute B19 infection was demonstrated in 12.6% (n = 21)
      of the children. Both tests were performed in 19 children and were positive in 10
      (53%). In 7 and 2 children, only B19-DNA or B19 IgM, respectively, was positive.
      Acute B19 infection was documented in 27% (10/39) of children who presented with
      a variety of acute exanthema diseases; 9% (5/57) of children with acute
      arthropathy (all 5 had transient synovitis); 10% (2/21) of children with fever >1
      week, both presented as mononucleosis syndrome; and in 44% (4/9) of children with
      transient pancytopenia or aplastic anemia. No acute B19 infection was
      demonstrated in 15 children with ITP, 9 with HSP, and 6 with aseptic meningitis
      and among 70 children in the control group. By logistic regression analysis,
      manifestations significantly associated with acute B19 infection were exanthema
      (OR 2.9; 95% CI = 1.1-7.5), anemia (OR 6.35; 95% CI = 2.2-18.2) and leucopenia
      (OR 4.14; 95% CI =1.2-14.2). CONCLUSIONS: Acute B19 infection was documented
      among 12.6% of children hospitalized with clinical syndrome potentially
      associated with the virus. Clinical and laboratory features associated with acute
      B19 infection were exanthema, anemia and leucopenia. Determination of both serum
      B19-DNA and serum B19 IgM should be performed for the accurate diagnosis of acute
      B19 infection.

PMID- 17006286
TI  - A community outbreak of conjunctivitis caused by nontypeable Streptococcus
      pneumoniae in Minnesota.
AB  - BACKGROUND: The Minnesota Department of Health (MDH) was notified of an outbreak
      of conjunctivitis in city A with cultures positive for Streptococcus pneumoniae.
      METHODS: MDH staff contacted clinics and schools in city A and city B regarding
      conjunctivitis cases, reviewed clinical findings of conjunctivitis cases in city
      A and collected isolates for subtyping. RESULTS: Between September 1 and December
      12, 2003, cities A and B reported 735 conjunctivitis cases. Fifty-one percent of
      the cases were reported from schools, childcare centers and colleges. Adults were
      more likely to report itching, burning or swelling of the eye(s); children were
      more likely to report crusty eyes (P < 0.05). Forty-nine percent of conjunctival
      cultures (71 of 144) were positive for S. pneumoniae. All isolates were
      nontypeable by serotyping. Pulsed field gel electrophoresis identified 3 clonal
      groups with 84% of isolates belonging to one clonal group. Multilocus sequence
      typing revealed that isolates had the same multilocus sequence type as isolates
      from a 2002 outbreak at a New England college. CONCLUSIONS: This outbreak was
      widespread in the community and conjunctivitis clinical presentation varied by
      age. The predominant strains in this outbreak were related to a pneumococcal
      strain implicated in prior conjunctivitis outbreaks, suggesting these strains
      have a predilection for causing conjunctivitis.

PMID- 17006287
TI  - Safety, tolerability and immunogenicity of VAQTA given concomitantly versus
      nonconcomitantly with other pediatric vaccines in healthy 12-month-old children.
AB  - BACKGROUND: The objective of this study is to assess whether hepatitis A vaccine
      is immunogenic and well tolerated when administered to 12-month-old children
      alone or concomitantly with other routinely administered pediatric vaccines.
      METHODS: Six hundred seventeen healthy 12-month-old children were randomized to
      receive dose 1 of hepatitis A vaccine given alone or concomitantly with measles
      mumps-rubella vaccine and varicella vaccine and dose 2 of hepatitis A vaccine
      given alone or concomitantly with diphtheria-tetanus-acellular pertussis vaccine
      and optionally with oral or inactivated poliovirus vaccine. Participants were
      followed for clinical adverse experiences and serologic responses to all vaccine
      antigens. Antibody responses were compared with historical controls for some
      indices. RESULTS: The safety profile was generally comparable whether hepatitis A
      vaccine was administered alone or concomitantly with other vaccines. When
      administered alone, the hepatitis A seropositivity rate was 98.3% and 100% for
      dose 1 and dose 2, respectively, and after dose 2 was similar to historical rates
      and the geometric mean titers were similar between initially seropositive and
      initially seronegative subjects (6207 and 6810 mIU/mL, respectively). After
      concomitant administration with hepatitis A vaccine, antibody responses to
      measles, mumps, rubella, diphtheria, tetanus and filamentous hemagglutinin
      (98.8%, 99.6%, 100%, 98.6%, 100% and 83.3%, respectively) were similar to
      historical controls and response to poliovirus was demonstrated, but immune
      responses to varicella zoster virus (79%) and pertussis toxoid (76%) were
      inferior to historical controls. CONCLUSIONS: Hepatitis A vaccine is highly
      immunogenic and generally well tolerated when administered to healthy children as
      young as 12 months of age regardless of initial hepatitis A serostatus and can be
      administered concomitantly with measles-mumps-rubella vaccine and oral or
      inactivated poliovirus vaccine.

PMID- 17006288
TI  - Immunogenicity, safety, and predictors of response after a pneumococcal conjugate
      and pneumococcal polysaccharide vaccine series in human immunodeficiency virus
      infected children receiving highly active antiretroviral therapy.
AB  - BACKGROUND: The immunogenicity and safety of 2 doses of pneumococcal conjugate
      vaccine (PCV) and 1 dose of pneumococcal polysaccharide vaccine (PPV) were
      evaluated in human immunodeficiency virus (HIV)-infected children receiving
      highly active antiretroviral therapy (HAART). METHODS: Children 2 to <19 years,
      receiving stable HAART for > or =3-6 months, with HIV RNA PCR <30,000-60,000
      copies/mL, received 2 doses of PCV and 1 dose of PPV at sequential 8-week
      intervals. Antibodies to pneumococcal serotypes (STs) 1 (PPV only) and 6B, 14,
      19F, and 23F (PCV and PPV) were measured by ELISA. RESULTS: Two hundred sixty
      three subjects were enrolled, of whom 225 met criteria for inclusion in the
      primary dataset. Antibody concentrations were low at entry, despite previous PPV
      in 75%. After vaccination, 76%-96% had concentrations > or =0.5 microg/mL and 62
      88% > or =1.0 microg/mL to the 5 STs (geometric mean concentrations [GMCs] = 1.44
      4.25 microg/mL). Incremental gains in antibody concentration occurred with each
      vaccine dose. Predictors of response included higher antibody concentration at
      entry, higher immune stratum (based on nadir CD4% before HAART and CD4% at
      screening), lower entry viral RNA, longer duration of the entry HAART regimen,
      and age <7 years. Response was more consistently related to screening CD4% than
      nadir CD4%. Seven percent had vaccine-related grade 3 events, most of which were
      local reactions. CONCLUSIONS: Two PCVs and 1 PPV were immunogenic and safe in HIV
      infected children 2 to <19 years who were receiving HAART. Responses were
      suggestive of functional immune reconstitution. Immunologic status based on nadir
      and, especially, current CD4% and control of HIV viremia were independent
      determinants of response.

PMID- 17006289
TI  - Tuberculosis in adolescents: A French retrospective study of 52 cases.
AB  - BACKGROUND: The only available data about tuberculosis (TB) among adolescents
      date back to the 1980s, although the incidence of tuberculosis has been
      increasing in this age group. METHODS: Medical records were reviewed for all
      adolescents aged 12 to 18 years hospitalized with the diagnosis of TB in
      Avicenne/Jean Verdier Teaching hospital (Seine-Saint-Denis, suburb of Paris)
      between September 2000 and December 2004. RESULTS: Of the 52 patients identified,
      52% were female. Median age at diagnosis was 15 years (range, 12-18 years). The
      proportion of adolescents known to be born abroad was 90%. Diagnoses resulted
      from the examination of a sick child in 79% of cases, a case contact
      investigation of an adult suspected of having TB in 19% and routine tuberculin
      skin test in 2%. Twenty-seven of 52 patients (52%) had isolated pulmonary
      disease. Sixteen patients (31%) had pulmonary and extrapulmonary TB and 8 cases
      (17%) had exclusively extrapulmonary disease. The site of extrapulmonary TB
      included pleural (n = 8), meningitis (n = 4), lymph node (n = 4), peritoneal (n =
      5), osteoarticular (n = 3) and genitourinary (n = 1). TB was confirmed by the
      isolation of Mycobacterium tuberculosis from sputum (n = 21), gastric aspirate (n
      = 8), bone (n = 1) or cerebrospinal fluid (n = 2). No case had a relapse or
      recurrence of disease in median 3.2 years of follow up. CONCLUSIONS: Our results
      indicate that demographic and clinical characteristics of adolescents with TB
      differed from adults and children. A specific approach to the prevention and
      treatment of TB in adolescents is absolutely necessary.

PMID- 17006290
TI  - Multiple needle-stick injuries with risk of human immunodeficiency virus exposure
      in a primary school.
AB  - Twenty children received needle-stick injuries with a risk of exposure to human
      immunodeficiency virus type 1 during an incident in a primary school playground.
      All were counseled and offered human immunodeficiency virus postexposure
      prophylaxis. All 20 children started postexposure prophylaxis, and 19 attended
      for follow-up testing 3 months later. More than one-half of the children
      completed the full 4-week course of treatment. None of the 19 children tested
      seroconverted after the incident.

PMID- 17006291
TI  - Managing and reporting community incidents: Ethical considerations.

PMID- 17006292
TI  - Early-onset neonatal sepsis in the era of widespread intrapartum
      chemoprophylaxis.

PMID- 17006293
TI  - Interferon-gamma release assays for diagnosis of tuberculosis infection in
      children.

PMID- 17006295
TI  - Serotypes, genotypes, and antibiotic susceptibility profiles of group B
      streptococci causing neonatal sepsis and meningitis before and after introduction
      of antibiotic prophylaxis.
AB  - We studied the characteristics of strains isolated from neonates with group B
      streptococci sepsis and meningitis, before and after the introduction of
      antibiotic prophylaxis in The Netherlands. In 1999, 1 year after this
      introduction the serotype and genotype distribution and the susceptibility
      patterns of the GBS strains had not changed. Penicillins remain drugs of first
      choice to prevent and treat neonatal GBS disease.

PMID- 17006294
TI  - Antibody persistence after primary vaccination with a hexavalent DTPa-HBV-IPV/HiB
      vaccine coadministered with a meningococcal C-CRM197 vaccine and response to a
      DTPa-IPV/HiB booster at 18 months of age.
AB  - Children 17-20 months of age (N = 344) received a diphtheria-tetanus toxoids
      acellular pertussis (DTPa)-inactivated poliovirus vaccine (IPV)/Haemophilus
      influenzae (Hib) booster after a 3-dose primary vaccination course with DTPa
      hepatitis B vaccine-IPV/Hib plus conjugate meningococcal C vaccine-CRM.
      Seroprotection rates were >80% (diphtheria, tetanus, hepatitis B, polio and
      polyribosylribitol phosphate) before and > or =96.6% (diphtheria, tetanus, polio
      and polyribosylribitol phosphate) after booster vaccination. The booster was well
      tolerated (fever >39.5 degrees C after <2% of doses; large swelling reactions
      after 6.3% of doses).

PMID- 17006296
TI  - Evaluation of malaria screening in newly arrived refugees to the United States by
      microscopy and rapid antigen capture enzyme assay.
AB  - Before an empiric malaria treatment program, >60% of Liberian refugees had
      malaria on arrival to Minnesota. We compared microscopy with rapid antigen
      testing for detecting asymptomatic parasitemia. Nine of 103 (8.7%) had malaria by
      polymerase chain reaction (blood smear and rapid testing had a sensitivity of
      22%). The empiric treatment program has decreased the rate of imported
      asymptomatic malaria. Blood film and rapid antigen testing are poor screening
      tests.

PMID- 17006297
TI  - A severe case of neonatal toxic shock syndrome-like exanthematous disease with
      superantigen-induced high T cell response.
AB  - Most newborn patients with a neonatal type of toxic shock syndrome (TSS), called
      neonatal TSS-like exanthematous disease (NTED), exhibit mild clinical symptoms.
      We present the case of a patient with NTED who exhibited exceptionally severe
      clinical symptoms and an adult-type T cell response to the causative toxin TSS
      toxin-1.

PMID- 17006298
TI  - Nonimmune hydrops fetalis and hepatitis in a neonate with congenital human
      immunodeficiency virus infection.
AB  - We present a case report of a term neonate with congenital human immunodeficiency
      virus (HIV) infection born with nonimmune hydrops fetalis who developed hepatitis
      shortly after birth. Maternal HIV infection was diagnosed after delivery. An
      extensive evaluation for known causes of nonimmune hydrops, both infectious and
      noninfectious, was negative. After beginning highly active antiretroviral
      therapy, hepatitis resolved and the HIV viral load became undetectable. We
      believe this is the first report of nonimmune hydrops fetalis and hepatitis in an
      infant with congenital HIV infection.

PMID- 17006299
TI  - Postinfection intravesical femoral head resulting in a vesicocutaneous fistula: A
      bizarre presentation and outcome.
AB  - Vesicocutaneous fistula can occur secondary to numerous factors. We present a
      case of 14-year-old girl who presented with a discharging sinus beside her labia
      majora with bony ankylosis of her left hip secondary to infection. Investigations
      revealed the femoral head protruding into the urinary bladder, resulting in a
      vesicocutaneous fistula. This case highlights the bizarre presentation of
      infection in the hip and the difficulty in diagnosis of a resultant
      vesicocutaneous fistula.

PMID- 17006301
TI  - Congenital candidiasis caused by different Candida species in a dizygotic
      pregnancy.

PMID- 17006300
TI  - Coxsackievirus B3 in human milk.
AB  - Coxsackievirus B3 can cause severe neonatal disease with high mortality. We
      present the first report of detection of coxsackievirus B3 in the mothers' milk
      of 2 severely infected neonates by culture and reverse transcriptase-polymerase
      chain reaction. Reverse transcriptase-polymerase chain reaction is a rapid and
      sensitive tool to detect coxsackievirus B3 in breast milk within few hours. By 12
      to 14 days after onset of symptoms, coxsackievirus B3 could not be detected in
      the breast milk of the symptomatic mothers.

PMID- 17006302
TI  - Human recombinant antibody against Candida.

PMID- 17006303
TI  - Tympanometry is not necessary in the diagnosis of acute otitis media.

PMID- 17006304
TI  - Sensitivity of surveillance for Haemophilus influenzae Type b meningitis.

PMID- 17006306
TI  - Molecular typing of pneumococci causing parapneumonic empyema in Spanish children
      using multilocus sequence typing directly on pleural fluid samples.

PMID- 17006307
TI  - Extended spectrum beta-lactamase-positive Escherichia coli bacteremia
      complicating rotavirus gastroenteritis.

PMID- 17006308
TI  - Antibiotic resistance mechanisms among pediatric respiratory and enteric
      pathogens: A current update.
AB  - Antibiotic resistance is a continually increasing problem that has, to a greater
      or lesser extent, affected virtually every area of the world. The scientific
      literature is abundant with papers related to antibiotics and antibiotic
      resistance. Many excellent papers and reviews have been published during the past
      few years, and the literature base continues to expand at rapid speed. This
      review is meant to provide a recent update on antibiotic resistance among
      respiratory and enteric pathogens, with a focus on infections in children. Not a
      small task, but this paper is not meant to be exhaustive. Rather, the intention
      is to highlight the key antibiotics and antibiotic resistance mechanisms that are
      currently the most relevant to pediatrics. The most recently published literature
      is used wherever possible, and the reader is encouraged to explore specific
      topics of interest further by reviewing the referenced literature.

PMID- 17006309
TI  - Selection of antibiotic-resistant pathogens in the community.
AB  - In recent years, the importance of the community as a breeding ground for
      antibiotic-resistant pathogens is being recognized. Prescription of antimicrobial
      drugs for viral infections, inadequate dosage, use of long-acting macrolides and
      broad-spectrum antibiotics, and accessibility of over-the-counter antibiotics in
      many countries are the main drivers of increasing resistance. Education of
      physicians and the public on the correct use of antibiotics, introduction of
      rapid and reliable laboratory methods to distinguish between viral and bacterial
      infections, and offering economic incentives to the pharmaceutical industry to
      develop new drugs appear to be key issues in the confrontation with this serious
      public health problem.

PMID- 17006310
TI  - Approaches to reduce antibiotic resistance in the community.
AB  - During the last two decades, there has been an alarming worldwide increase of
      resistance to antibiotics of bacterial pathogens responsible for community
      acquired infections. This dramatic evolution is generally attributed to the
      extensive use of antibiotics and the selective pressure on the bacterial strains.
      To decrease antibiotics resistance in the community, several approaches should be
      considered through: reducing unnecessary antibiotic prescriptions: inappropriate
      antibiotic treatments are becoming a major issue; however, few studies have shown
      a decrease of antibiotic resistance following a reduction of antibiotic use in
      the community;decreasing the prescriptions of the more selective antibiotic
      compounds for some bacterial species, eg macrolides and group A streptococcus
      (GAS), trimethoprim-sulfamethoxazole and pneumococcus; using an optimal dosage
      and duration of antibiotic regimens chosen; some studies have suggested that low
      dosage and long treatment duration could promote antibiotic resistance; and
      implementing the pneumococcal conjugate vaccines; several studies have shown a
      decline in the proportion of penicillin nonsusceptible Streptococcus pneumoniae
      isolated from invasive pneumococcal diseases or nasopharyngeal flora. The
      combination of these approaches, particularly the reduction of antibiotic use and
      pneumococcal immunization, could be synergistic.

PMID- 17006311
TI  - Will reduction of antibiotic use reduce antibiotic resistance?: The pneumococcus
      paradigm.
AB  - Community-acquired respiratory infections in general, and those caused by S.
      pneumoniae in particular, are the main reason for prescribing antimicrobials in
      young children. Antibiotic drug abuse is common. This is the basis for the
      initiative for the reduction in antibiotic use. However, failure to consider that
      not all antibiotics are similar in their effect on promotion of resistance has
      led to continuous emerging resistance. In the present article, the trends in
      prescribing antibiotics in young children and their interrelation with antibiotic
      resistance among clinical respiratory isolates of S. pneumoniae in children will
      be reviewed, along with theoretical considerations and research evidence that led
      to concluding that among antibiotics, the least resistance-promoting drug for S.
      pneumoniae is amoxicillin (+/- clavulanate), whereas oral cephalosporins and
      azithromycin demonstrate a higher resistance-promotion potential in the
      individual population in the community. Although antibiotics differ in their
      resistant-promotion potential, all still do promote resistance.

PMID- 17006312
TI  - The 10-year American Society of Plastic Surgeons' history update.

PMID- 17006313
TI  - Into the twenty-first century: the history of the American Society of Plastic
      Surgeons from 1995 to 2006.

PMID- 17006314
TI  - American Society of Maxillofacial Surgeons, 1997 to 2006: another decade of
      excellence in education and research.

PMID- 17006315
TI  - Live donor liver transplantation in adults.
AB  - Live donor liver transplantation (LDLT) was initiated in 1988 for children
      recipients. Its application to adult recipients was limited by graft size until
      the first right liver LDLT was performed in Hong Kong in 1996. Since then, right
      liver graft has become the major graft type. Despite rapid adoption of LDLT by
      many centers, many controversies on donor selection, indications, techniques, and
      ethics exist. With the recent known 11 donor deaths around the world, transplant
      surgeons are even more cautious than the past in the evaluation and selection of
      donors. The need for routine liver biopsy in donor evaluation is arguable but
      more and more centers opt for a policy of liberal liver biopsy. Donation of the
      middle hepatic vein (MHV) in the right liver graft was considered unsafe but now
      data indicate that the outcome of donors with or without MHV donation is about
      equal. Right liver LDLT has been shown to improve the overall survival rate of
      patients with chronic liver disease, acute or acute-on-chronic liver failure and
      hepatocellular carcinoma waiting for liver transplantation. The outcome of LDLT
      is equivalent to deceased donor liver transplantation despite a smaller graft
      size and higher technical complexity.

PMID- 17006316
TI  - Implications of ABO error rates in proficiency testing for solid organ
      transplantation.

PMID- 17006317
TI  - Cardiovascular disease management in renal transplant recipients: more or less
      treatment?

PMID- 17006318
TI  - Rapamycin and dendritic cells: keep on movin'.

PMID- 17006319
TI  - Development of de novo cancer in p53 knock-out mice is dependent on the type of
      long-term immunosuppression used.
AB  - BACKGROUND: Development of cancer in transplant recipients may be influenced by
      different immunosuppressive agents. Recent publications suggest that rapamycin
      (RAPA), or possibly mycophenolate mofetil (MMF), may reduce established tumor
      growth; however, experimental data is lacking for de novo cancer prevention.
      METHODS: We tested the effects of long-term immunosuppression on spontaneous
      tumor formation in p53 knock-out mice. Mice received no treatment, or were given
      RAPA, MMF, or cyclosporine (CsA) starting on week nine after birth, with the
      experimental endpoint being week 29. RESULTS: All (9/9) untreated mice developed
      clinically evident tumors before week 26, as confirmed by histology (6 lymphomas,
      2 sarcomas, 1 lymphoma+sarcoma). All CsA-treated mice (9/9) also developed
      clinical tumors before the endpoint (7 lymphomas, 1 sarcoma, 1 lymphoma+sarcoma).
      With MMF, 7/10 mice showed clinical evidence of tumor before the experimental
      endpoint (4 lymphomas, 2 sarcomas, 1 lymphoma+sarcoma), however, histologic
      tissue analysis revealed that the remaining three mice had subclinical cancer (3
      lymphomas). In contrast, RAPA treatment resulted in only three mice with clinical
      tumors (all lymphomas), with histology revealing subclinical lymphomas in three
      additional mice, but no evidence of cancer in four animals. Statistically, cancer
      development was decreased with RAPA treatment (P=0.002), but was not affected
      with either MMF or CsA (P>0.10). CONCLUSION: These experiments are the first to
      show immunosuppression under RAPA can reduce spontaneous de novo cancer
      associated with p53 mutations. Although neither CsA nor MMF treatment affects p53
      associated tumor incidence, MMF may have some tendency to reduce clinical tumor
      appearance.

PMID- 17006320
TI  - Impact of parathyroid hormone on bone density in long-term renal transplant
      patients with good graft function.
AB  - BACKGROUND: It remains unknown whether low-grade hyperparathyroidism persisting
      beyond the first year postrenal transplantation has any impact on bone density.
      METHODS: Parathyroid hormone (PTH), glomerular filtration rate (GFR), and bone
      density (by dual-energy x-ray absorptiometry [DXA]) were monitored in the follow
      up of our transplant patients. Of 260 long-term renal transplant patients, 41
      fulfilled the following criteria: Two DXA measurements performed at least five
      years apart (median 6.8 years, range 5-9); GFR>or=35 ml/min per 1.73 m body
      surface area (median 50, range 35-76); no bisphosphonate treatment or
      parathyroidectomy in the study period. RESULTS: In all, 40% had mean PTH values
      above the normal limit 6.9 pmol/L (65 pg/ml), and the range was 0.9-17 pmol/L. In
      the first DXA, 8 of 41 patients had osteoporosis and 17 more had osteopenia. Hip
      bone density Z-score was -0.60 SD, range (-2.6 to +2.3). The absolute median
      value (g/cm) remained unchanged until the second DXA, but among patients there
      was a variation which ranged from -2.3% to +1.7% per year. In a simple linear
      regression analysis, these changes were significantly correlated to mean PTH
      (r=0.16, P=0.010). Median lumbar spine bone density was also reduced in the first
      DXA and was not different at follow-up, but with this variable individual changes
      did not correlate to mean PTH. CONCLUSION: Bone density is often reduced and PTH
      remains elevated in long-term renal transplant patients with good transplant
      function. Slight to moderate elevation of PTH is associated with reduction in hip
      bone mineral density.

PMID- 17006321
TI  - Utility of cell-cycle modulators to predict vascular invasion and recurrence
      after surgical treatment of hepatocellular carcinoma.
AB  - BACKGROUND: The outcome of surgical treatment of hepatocellular carcinoma (HCC)
      could be improved by applying patient selection criteria based on tumoral
      aggressiveness. Here we analyzed the prognostic role of the expression of several
      genes involved in cell-cycle regulation in a group of patients with HCC. METHODS:
      We retrospectively studied 93 patients (67 transplanted and 26 resections)
      treated between 1996 and 2000. In micro-thick sections from paraffin-embedded
      tumoral tissues, the expression of p53, pRb, p16, and cyclin D1 was analyzed. A
      logistic regression model was used to detect factors related to vascular
      invasion. A Cox regression model was applied to identify pathologic and molecular
      factors with the capacity to predict the recurrence of HCC. RESULTS: Only tumor
      size>3 cm (odds ratio [OR]: 3.4; 95% CI: 1.2-9.9; P=0.019) and pRb expression
      (OR: 4.1; 95% CI: 1.02-17; P=0.053) were associated with an increased risk of
      vascular invasion. The regression model applied to the group of transplanted
      patients showed three factors that were independently related to recurrence:
      vascular invasion (OR 7.5; 95% CI: 1.1-51.8; P=0.039); pRb expression (OR: 11;
      95% CI: 1.2-96.9; P=0.03); and p16 expression (OR: 69.7; 95% CI: 5.1-9448;
      P=0.001). In the group of resected patients, pRb expression was associated with
      higher risk of recurrence only in the univariate analysis (P=0.037). The
      multivariate analysis showed tumor size>3 cm (OR: 57.5; 95% CI: 1.1-51.8;
      P=0.039) and vascular invasion (OR: 6.1; 95% CI: 1.05-35.3; P=0.044) to be
      significantly associated with recurrence. CONCLUSIONS: Of the molecular factors
      studied, only pRb expression was useful as a predictive factor of vascular
      invasion in patients with HCC, and also of recurrence in transplanted patients
      with this carcinoma. pRb expression may be relevant to consider when selecting
      patients for resection and when identifying transplanted patients with a high
      risk of recurrence.

PMID- 17006322
TI  - Recurrence of IgA nephropathy among renal allograft recipients from living donors
      is greater among those with zero HLA mismatches.
AB  - BACKGROUND: Risk factors contributing to recurrence of IgA nephropathy (IgAN)
      after transplantation are unclear. Some (but not all) series have suggested
      greater degrees of human leukocyte antigen (HLA) matching play a role. METHODS:
      Using registry data including all kidney transplants performed in Australia and
      New Zealand between 1987 and 2004 we examined IgAN recurrence among living donors
      with zero HLA-mismatches. RESULTS: Of 1354 grafts performed in recipients with
      IgAN, live donors (LDs) accounted for 488 including 108 with zero HLA-mismatches.
      Biopsy-proven IgAN recurrence was reported for 110 (7%) of grafts overall, but
      17% of those who received zero HLA-mismatched LD grafts (HR for recurrence free
      graft survival 2.7 [95% CI 1.5-5.1], P=0.001). There was no significant
      difference in recurrence rates between zero and >or=1 HLA-mismatched grafts from
      cadaveric donors (CDs). Recurrence of IgAN was associated with worse graft
      survival, more so among LD recipients (HR 8.5 [4.8-15.2], P<0.001) than CD
      recipients (HR 4.5 [2.6-7.5], P<0.001). However, there was no difference in graft
      survival between zero and >or=1 HLA mismatched LD recipients whose native disease
      was IgAN. In contrast, zero HLA mismatched recipients of kidneys with other
      primary renal disease enjoyed a graft survival advantage. No difference in
      recurrence rates was seen among those with HLA B12, B35 or DR4. CONCLUSIONS: The
      increased rates of IgAN-related graft loss among zero HLA-mismatched LD
      recipients counterbalance the advantage normally seen among zero HLA-mismatched
      recipients. However, since graft survivals are similar, there is no reason to
      avoid donor-recipient pairs with zero HLA-mismatches in this setting.

PMID- 17006323
TI  - Subclinical inflammation and prothrombotic state in heart transplant recipients:
      impact of cyclosporin microemulsion vs. tacrolimus.
AB  - BACKGROUND: Subclinical inflammation is related to adverse events in patients
      with coronary artery disease. In the present study, we determined the changes in
      hemostatic parameters and inflammatory markers in a large cohort of dyslipidemic
      cardiac transplant recipients compared with dyslipidemic healthy controls, and
      the effect of cyclosporin microemulsion (CsA) vs. tacrolimus immunoprophylaxis on
      these parameters. METHODS: Stable cardiac transplant recipients (n=129) aged
      56.7+/-10.1 years, 79+/-42 months postcardiac transplantation, and 26 mildly
      dyslipidemic healthy control subjects had serum measurements for lipids and
      lipoproteins, hemostatic parameters, and selected inflammatory markers.
      Transplant recipients were randomized to either continuation of CsA maintenance
      or conversion to tacrolimus immunoprophylaxis and were reassessed after six
      months. RESULTS: CsA-maintained cardiac transplant recipients exhibited a
      significant elevation in Factor VIII, Von Willebrand factor, fibrinogen and PAI-I
      compared with healthy control subjects (all P<0.05). Similarly, cardiac
      transplant patients yielded a significantly elevated C-reactive protein (CRP)
      (4.11+/-6.25 [transplant group (TX)] vs. 2.09+/-2.21 mg/L [control group (CTL)];
      P=0.0195), and homocysteine (19.2+/-8.8 [TX] vs. 9.70+/-2.45 microM [CTL];
      P<0.001). VCAM, ICAM, E- and P-selectins were also significantly higher in
      transplant patients than in controls (all P<0.05). The conversion from CsA to
      tacrolimus resulted in a significant decrease in uric acid, total- and LDL
      cholesterol, apolipoprotein B, creatinine, and homocysteine levels (all P<0.05).
      CONCLUSIONS: Stable long-term CsA-maintained cardiac transplant patients exhibit
      a significant and general increase in hemostatic parameters and markers for
      subclinical inflammation. Tacrolimus conversion improved the patient lipid
      profile and decreased serum creatinine, uric acid, and homocysteine without any
      significant effect on the other markers.

PMID- 17006324
TI  - Effect of atorvastatin therapy and conversion to tacrolimus on
      hypercholesterolemia and endothelial dysfunction after renal transplantation.
AB  - BACKGROUND: Hypercholesterolemia is a frequent complication in renal transplant
      patients treated with cyclosporine A (CsA). Whether it is preferable to treat
      hypercholesterolemia with statins or to switch patients from CsA to tacrolimus
      (TRL) has not been investigated. METHODS: Twelve CsA-treated kidney transplant
      recipients with hypercholesterolemia were successively crossed over from CsA
      alone to: CsA plus atorvastatin; TRL alone; and TRL plus atorvastatin. Total
      cholesterol (C), Low density lipoprotein (LDL)-C, high density lipoprotein (HDL)
      C, LDL and HDL alpha-tocopherol content, lag-time of LDL oxidation, plasma levels
      of oxidized LDL and the percentage of small dense LDL were assayed at the end of
      each treatment period. Endothelial function was assessed by high resolution
      ultrasound measurement of flow-mediated brachial artery vasodilatation (FMD).
      RESULTS: Atorvastatin therapy was more efficient in reducing total cholesterol
      and LDL-C levels than conversion from CsA to TRL. Combining TRL with atorvastatin
      further reduced LDL-C levels as compared to TRL alone, but was no more efficient
      than the CsA-statin combination. Neither atorvastatin therapy nor conversion to
      TRL significantly changed the proportion of dense LDL, lipoprotein alpha
      tocopherol contents or the lag time of LDL oxidation. Addition of atorvastatin to
      CsA increased FMD from 4.0+/-1.8% to 6.5+/-4.0% (P<0.05 vs. CsA). Conversion from
      CsA to TRL caused a slight improvement in FMD (5.1+/-2.1%, P<0.05 vs. CsA).
      Adding atorvastatin to TRL had no detectable effect on FMD (5.5+/-2.3%, P=NS vs.
      TRL). CONCLUSIONS: Atorvastatin was more efficient in reducing total and LDL
      cholesterol levels of CsA-treated renal transplant patients than conversion to
      TRL and significantly improved endothelial dysfunction.

PMID- 17006325
TI  - Impairment of circulating myeloid dendritic cells in immunosuppressed
      renal/pancreas transplant recipients.
AB  - BACKGROUND: Immunosuppressive drugs used after organ transplantation are known to
      impair lymphocyte function, resulting in an increased incidence of viral
      associated malignancies. In vitro data indicate that immunosuppressive drugs also
      target dendritic cells (DCs). Our study aimed to investigate the phenotype and
      function of circulating myeloid DCs (mDCs) from renal/pancreas transplant
      recipients receiving immunosuppressive drugs. In addition, we analyzed the
      potential of patient monocytes to differentiate into mature DCs (MoDCs) in vitro.
      METHODS: Phenotype of mDCs was analyzed by fluorescence-activated cell sorter
      (FACS) analysis. The ability of mDCs to undergo activation was determined using
      cytokine bead array and FACS analysis. Allostimulatory capacity was determined by
      mixed leukocyte reaction. MoDCs were generated using a defined cytokine cocktail
      and analyzed for maturity of phenotype and function. The ability of patient-MoDCs
      to expand antigen-specific T cells was analyzed by tetramer staining and
      interferon (IFN)-gamma ELISPOT assay. RESULTS: We observed a reduced expression
      of CD54 (P=0.001), CD86 (P=0.032), HLA-DR (P=0.013), and CD38 (P=0.006) on
      patient mDCs. Upon stimulation, the expression of HLA-ABC, HLA-DR and CD86 was
      upregulated on patient mDCs to the same level as on control mDCs. MoDCs were
      equivalent to control-MoDCs regarding phenotype and function. Co-culture of
      peptide-pulsed patient-MoDCs with T cells resulted in significant expansion of
      autologous Epstein-Barr virus-specific, IFN-gamma secreting T cells. CONCLUSIONS:
      Our data support the notion that immunosuppressive drugs target DCs and induce a
      maturation defect in circulating mDCs. However, ex vivo stimulated mDCs as well
      as MoDCs do not show a significant impairment, suggesting that MoDCs from
      immunosuppressed patients can be used for immunotherapeutic strategies.

PMID- 17006326
TI  - Serological viral testing of cadaveric cornea donors.
AB  - BACKGROUND: Cornea graft recipients are exposed to viral transmission from the
      donor. Cadaveric donor serum is often of poor quality and frequently yields
      falsely positive results in serological assays that may result in the graft being
      needlessly discarded. OBJECTIVE: We examined the influence of the time of blood
      collection after death, and the macroscopic aspect of serum, on serological test
      results in cadaveric cornea donors. METHODS: Five hundred sixty-five consecutive
      cadaveric cornea donors were systematically tested for serological markers of
      human immunodeficiency virus type 1 and 2, human T-cell leukemia virus type 1,
      hepatitis B and hepatitis C viruses (HCV). We studied the influence of the
      macroscopic aspect of the donor's serum and the time of blood collection after
      death on the results of serological testing and on the subsequent decision to use
      or discard the graft. RESULTS: Twenty-one and a half percent of corneas were
      rejected on the basis of virological test results. We found significant
      relationships between the macroscopic aspect of serum at the time of testing and:
      (i) a positive, equivocal or discrepant result of immunoassays, for all markers
      except anti-HCV antibodies, (ii) non acceptance of cornea grafts, and (iii) the
      time of blood sampling after death. CONCLUSIONS: The macroscopic aspect of
      postmortem blood samples is the best predictor of the specificity of serological
      testing in cornea donors. Serological results should be interpreted with care
      when serum is macroscopically abnormal, and cadaveric donors should not be
      sampled more than 12 hr after death.

PMID- 17006327
TI  - Ex vivo lentivirus transduction and immediate transplantation of uncultured
      hepatocytes for treating hyperbilirubinemic Gunn rat.
AB  - BACKGROUND: Ex vivo liver gene therapy provides an attractive alternative to
      orthotopic liver transplantation for the treatment of liver diseases. We
      previously reported a protocol in which human primary hepatocytes are highly
      transduced in Suspension with Lentiviral vectors and Immediately Transplanted
      (SLIT). Here, we evaluated the SLIT approach in Gunn rats, the animal model for
      Crigler-Najjar syndrome type 1, a defect in bilirubin UDP-glucuronosyltransferase
      (BUGT). METHODS: We constructed lentiviral vectors coding for BUGT under control
      of an ubiquitous promoter. Control vectors contained Green Fluorescent Protein
      (GFP) under control of the same promoter. Hepatocytes were isolated from
      jaundiced Gunn rats and transduced in suspension for four hr. After washing, 2x10
      hepatocytes were immediately transplanted into syngeneic rats. Bilirubinemia and
      bile pigments were regularly assessed after cell transplantation. The percentage
      and presence of transduced hepatocytes was analyzed by immunohistochemistry in
      GFP-transplanted animals. RESULTS: In rats receiving BUGT-transduced hepatocytes,
      bilirubinemia decreased by about 30%. The level of correction remained stable for
      up to 240 days. Bilirubin glucuronides were present in the bile of treated
      animals, indicating the metabolic activity of engrafted hepatocytes. In contrast,
      bilirubinemia in GFP-transplanted rats did not decline but rather increased. GFP
      positive hepatocytes amounted to 0.5-1% of the liver, which is in agreement with
      the number of transplanted and genetically-modified hepatocytes (6x10).
      CONCLUSIONS: This work reports the first demonstration of long-term metabolic
      benefit after rapid transplantation of ex vivo lentivirally tranduced
      hepatocytes. Therefore, this study demonstrates the therapeutic proof-of
      principle and potential of the SLIT approach for treating inherited metabolic
      liver diseases.

PMID- 17006328
TI  - Use of sphingosine-1-phosphate 1 receptor agonist, KRP-203, in combination with a
      subtherapeutic dose of cyclosporine A for rat renal transplantation.
AB  - BACKGROUND: We demonstrate the long-term effectiveness of KRP-203 treatment in
      combination with a subtherapeutic dose of cyclosporine A (CsA) on rat renal
      allografts. METHODS: We tested the effect of KRP-203 in combination with CsA
      using a rat skin allograft model. The Pharmacokinetic interaction between CsA and
      KRP-203 was evaluated. The selectivity of KRP-203 for sphingosine-1-phosphate
      (S1P)1 and S1P3 receptors were investigated in vitro. Heart rate alteration
      following bolus injection of phosphorylated KRP-203 (KRP-203-P) or FTY720 (FTY720
      P) was also monitored in rats. Finally, the long-term effectiveness of KRP-203 in
      conjunction with a low dose of CsA was investigated in a rat renal
      transplantation model. RESULTS: Administration of KRP-203 with CsA prolonged skin
      allograft survival. KRP-203 and CsA had no effect on the pharmacokinetics of the
      other. While FTY720-P activated both S1P1 and S1P3 receptors, KRP-203-P
      selectively activated S1P1, but not the S1P3 receptor (EC50:>1000 nM). Compared
      to FTY720-P, a tenfold higher dose of KRP-203-P was necessary to induce transient
      bradycardia. With a low dose of CsA (1 mg/kg/day), KRP-203 (0.3 mg/kg/day)
      significantly prolonged renal allograft survival (P<0.05, survival time: 9.8 days
      (CsA) vs. >27.4 days (CsA+KRP)). Although a higher dose of CsA (3 mg/kg/day)
      alone kept recipients alive, this caused severe renal graft dysfunction. Use of
      KRP-203 (3 mg/kg/day) in conjunction with CsA markedly improved graft function
      (P<0.05, creatinine clearance: 0.41+/-0.25 ml/min [CsA] vs. 1.15+/-0.16 ml/min
      [CsA+KRP]). CONCLUSIONS: The selectivity of KRP-203 for S1P1 reduces the risk of
      bradycardia, and the combination therapy of KRP-203 with CsA represents a safe
      and effective strategy for use in renal transplantation.

PMID- 17006329
TI  - Tumor necrosis factor-alpha production by human islets leads to postisolation
      cell death.
AB  - BACKGROUND: Recent successes in islet transplantation highlight the importance of
      islet isolation by experienced centers and minimization of cell injury as crucial
      to the achievement of insulin independence. Islet injury may manifest as cell
      death by apoptosis, shorter graft survival, and the need for retransplantation.
      Although an inflammatory cytokine response at the graft site is known to inhibit
      engraftment, recent evidence indicates that islet cells may contribute to this
      response. METHODS: Isolated human islets were cultured for up to one week in
      serum-free CMRL-1066 with 25 microM of tumor necrosis factor (TNF)alpha inhibitor
      RDP58. Gene expression was measured by reverse transcriptase polymerase chain
      reaction, apoptosis and TNFalpha secretion by enzyme-linked immunosorbent assay
      and enzyme-linked immunospot, and islet function by stimulated insulin secretion.
      RESULTS: Isolation induced a twofold increase in TNFalpha expression between days
      one and three (P<0.05), while TNFalpha secretion peaked at day one. RDP58 reduced
      TNFalpha secretion by 70.6% (P<0.02), though TNFalpha gene expression was
      unaffected. RDP58 reduced the frequency of TNFalpha-secreting islets by 64.4%
      (P<0.05) and reduced apoptotic levels by 26.4% within 24 hr postisolation
      (P<0.05). The reduction in apoptosis was maintained throughout the week (P<0.01),
      while apoptosis increased in control cultures. Finally, RDP58-treated islets
      displayed increased insulin secretion in response to both elevated glucose
      (1915.0+/-396.6 vs. 825.3+/-261.1 mU/L, P<0.01) and secretagogues (2294.3+/-529.5
      vs. 939.8+/-333.7 mU/L, P<0.02). CONCLUSIONS: These data demonstrate that
      intraislet cytokine production should be considered as a factor leading to islet
      cell death postisolation and postengraftment, and strategies aimed at countering
      islet cytokine production represent a novel target for improving islet viability
      and function.

PMID- 17006330
TI  - Monitoring antidonor alloantibodies as a predictive assay for renal allograft
      tolerance/long-term observations in nonhuman primates.
AB  - BACKGROUND: In an effort to define reliable assays that might predict
      postimmunosuppressant-withdrawal development of chronic rejection (CR), despite
      conditioning for tolerance induction, we evaluated various immunological
      responses in nonhuman primate renal allograft recipients. METHODS: Fourteen
      Cynomolgus monkeys received low dose total body irradiation, thymic irradiation,
      antithymocyte globulin, and peritransplant CD154 blockade, followed by a one
      month course of cyclosporine. Recipients underwent major histocompatibility
      complex mismatched kidney transplantation with donor bone marrow infusion (Group
      A, n=8), without donor cell infusion (Group B, n=2), or with donor splenocyte
      infusion (Group C, n=4). RESULTS: All Group A recipients developed mixed
      chimerism and four of them survived long-term without rejection. The remaining
      four rejected their kidney allografts either chronically or acutely. All
      recipients in Groups B and C failed to develop chimerism and rejected their
      allografts. Among various in vitro assays, detection of anti-donor alloantibody
      (ADA) by flow cytometry (FCM) was the most relevant to long-term outcome. All
      five recipients that developed both anti-T cell and B cell IgG ADA in Groups A, B
      and C, developed histological evidence of CR within 200 days of the appearance of
      ADA. One of two recipients that developed only anti-B cell IgG ADA eventually
      developed CR over two years following discontinuation of immunosuppression and
      1.5 years after ADA development. Another recipient with very low anti-B cell ADA
      has never developed CR. CONCLUSION: ADA monitoring with FCM assay appears to be
      useful in predicting the failure of tolerance prior to the development of
      functional or histologic abnormalities of the renal allograft.

PMID- 17006331
TI  - Differential effects of immunosuppressive drugs on chemokine receptor CCR7 in
      human monocyte-derived dendritic cells: selective upregulation by rapamycin.
AB  - BACKGROUND: Appropriate recruitment of dendritic cells (DC) at sites of
      inflammation and migration to secondary lymphoid organs is of critical importance
      for the initiation of Ag-specific immune responses. The proper localization of DC
      in selected tissues is guided primarily by the coordinated expression of
      chemokine receptors (CKR). Here we show that immunosuppressive drugs have
      divergent effects on the modulation of CKR in maturing DC. METHODS AND RESULTS:
      Dexamethazone (DEX) and IL-10 inhibited human DC migration to CCL19 in vitro and
      mouse DC migration to lymph nodes (LN) in vivo, by impairing CCR7 expression. The
      calcineurin inhibitors cyclosporine A (CsA) and tacrolimus (FK506) were
      characterized by the inability to modulate CKR expression and migratory activity.
      Rapamycin (RAPA) increased DC migration to CCL19 in vitro and to LN in vivo by
      enhancing CCR7 expression. This effect could be mediated, in LPS-maturing DC, by
      the inhibition of autocrine IL-10 production. The in vivo data obtained with ex
      vivo RAPA treated DC were confirmed in a model of in vivo drug administration in
      mice, suggesting a potential clinical relevance. CONCLUSIONS: These findings
      demonstrate that immunosuppressive agents differently modulate the CKR switch
      associated with maturing DC; in particular, RAPA selectively up-regulates CCR7
      and enhances the migration of differentiated DC to regional LN. This study
      contributes to a better understanding of the role of immunosuppressive therapy on
      DC migration, a potentially relevant check point of immunosuppressive treatment.

PMID- 17006332
TI  - Enteral feeding and early outcomes of patients undergoing allogeneic stem cell
      transplantation following myeloablative conditioning.
AB  - The purpose of this study was to evaluate the impact of enteral nutrition on
      early outcome of patients after myeloablative allogeneic stem cell
      transplantation (allo-SCT). From January 2001 to January 2003, 22 patients agreed
      to receive enteral nutrition via a nasogastric feeding tube; the remaining 23
      patients received parenteral nutrition (n=22) or standard oral feeding (n=1).
      Early complications and factors influencing 100-day overall survival (OS) were
      investigated. Patients who received enteral nutrition developed less often acute
      grade III/IV graft-versus-host disease (18%) than those who did not (35%)
      (P=0.011). In addition, this group showed lower mortality from infection during
      the first 100 days after transplantation. In multivariate analyses, only the
      absence of enteral nutrition was found to adversely influence 100-day OS with a
      hazard ratio of 8.3. Enteral nutrition is a safe and effective method for feeding
      allo-SCT patients. A randomized trial is warranted to confirm its advantage on
      early patient outcome.

PMID- 17006333
TI  - Adult T-cell leukemia development from a human T-cell leukemia virus type I
      carrier after a living-donor liver transplantation.
AB  - Adult T-cell leukemia (ATL) develops in a human T-cell leukemia virus type I
      (HTLV-I) carrier. The development of malignancy during immunosuppressive
      treatment following organ transplantation is one of the late fatal complications.
      We describe the development of three cases of ATL in eight HTLV-I carriers within
      164 living-donor liver transplant recipients undergoing immunosuppressive
      treatment. All three cases were immunosuppressed with tacrolimus. Acute-type ATL
      was diagnosed at 6, 9, and 25 months after living-donor liver transplantation,
      based on increased numbers of CD4+25+ lymphocytes exhibiting "flower-like"
      nuclei, and the elevation of lactate dehydrogenase. Southern blot analysis
      demonstrated the clonal proliferation of ATL cells in peripheral blood. The ATL
      cells originated from the recipient, as demonstrated by fluorescence in situ
      hybridization analysis using sex chromosomal markers. Our observations suggest
      that immunosuppressive treatment for the prevention of graft rejection after
      living-donor liver transplantation may induce the development of ATL in an HTLV-I
      carrier.

PMID- 17006334
TI  - The ratio of interferon-gamma and interleukin-10 producing donor-specific cells
      as an in vitro monitoring tool for renal transplant patients.
AB  - If in vitro tools can be used to predict which renal transplant patients are at
      risk for rejection and which patients are more predisposed to tolerance, the
      immunosuppressive regimen can be adjusted to prevent rejection before it becomes
      clinically apparent or, in case of a tolerant patient, medication can be reduced
      or even stopped. Peripheral blood mononuclear cells (PBMC) of patients with
      persistent stable graft function and of patients with (biopsy-confirmed) acute
      rejection were stimulated with donor cells and tested with Elispot analysis. A
      significantly higher number of donor-specific interferon (IFN)-gamma producing
      cells were found in patients with rejection, as determined with Elispot analysis.
      Furthermore, a trend towards a higher number of interleukin (IL)-10 producing
      cells was found in patients with stable graft function. The ratio of IFN-gamma/IL
      10 producing cells showed to be the best tool to discriminate between
      nonrejecting patients and rejecting patients.

PMID- 17006335
TI  - Occult nephrolithiasis in prospective kidney donors: a source for hematuria.

PMID- 17006336
TI  - Inactivity of hidradenitis suppurativa after renal transplantation.

PMID- 17006337
TI  - Dengue shock syndrome in a liver transplant recipient.

PMID- 17006339
TI  - Audiology & otolaryngology.

PMID- 17006338
TI  - KSHV/HHV-8 infection of tubular epithelial cells in transplantation kidney.

PMID- 17006340
TI  - Technical note on microcatheter implantation for local inner ear drug delivery:
      surgical technique and safety aspects.
AB  - HYPOTHESIS: Despite its invasiveness, the temporary implantation of a
      microcatheter into the middle ear cavity is an appropriately safe method for
      providing continuous drug delivery to the inner ear. BACKGROUND: For the
      application of drugs to the inner ear, different delivery strategies are
      available ranging from intratympanic injections to temporarily implanted
      microcatheters. It has recently been demonstrated that the choice of the drug
      delivery system influences the pharmacokinetics in the inner ear. If a continuous
      drug application over several weeks is required, a secure placement of the
      delivery device (i.e., the microcatheter) is necessary to guarantee efficient
      drug delivery and to avoid unwanted side effects. STUDY DESIGN: Retrospective
      chart review. MATERIALS AND METHODS: During 2000 to 2005, 25 patients with acute
      unilateral severe-to-profound hearing loss or anacusis and failure of systemic
      high-dose glucocorticoid and rheological therapy were offered an intratympanic
      delivery of glucocorticoids via a temporarily implanted catheter and an external
      pump for up to 4 weeks as a salvage treatment option. The standardized surgical
      implantation and fixation technique developed for the microcatheter were
      characterized by six elements: 1) a medial and a lateral tunnel connected by a
      groove in the posterior wall of the bony ear canal, 2) stabilization of the
      catheter with bone wax and soft tissue plugs in the tunnels, 3) an ear canal
      packing, 4) a series of fixating sutures along the catheter, 5) an adhesive
      dressing, and 6) additional tapes at the connecting line between pump and
      catheter. At the end of the implantation period, the catheter was removed by a
      second surgical procedure allowing for evaluation of the catheter position and
      the condition of the middle ear space. RESULTS: Adverse events included catheter
      dislocation, catheter obstruction, formation of mild granulation tissue in the
      middle ear cavity, tympanic membrane defects, and ear canal skin defects. With
      introduction of an improved implantation and fixation technique, the number of
      catheter dislocations could be significantly reduced. No complications were
      observed on long-term follow-up. CONCLUSION: If the pharmacokinetics or
      pharmacodynamics of a specific local inner ear therapy approach requires a
      continuous intratympanic drug application (e.g., to restore hearing in patients
      with severe or profound hearing loss), the temporary implantation of a
      microcatheter by a standardized surgical technique is a feasible and
      appropriately safe method for providing continuous drug delivery to the inner
      ear.

PMID- 17006341
TI  - Elimination of facial nerve stimulation by reimplantation in cochlear implant
      subjects.
AB  - HYPOTHESIS: Perimodiolar intracochlear electrodes with contacts facing towards
      the modiolus have limited current flow towards the outer wall of the cochlea and
      therefore, may reduce the occurrence of facial nerve stimulation (FN) in cochlear
      implant subjects. BACKGROUND: Facial nerve stimulation is a well-known
      complication in cochlear implant treatment especially in the group of subjects
      with otosclerosis. The possible explanation of this side effect is a change of
      the electrical properties of the otosclerotic bone leading to leakage current and
      resulting in facial nerve stimulation. METHODS: Four CI subjects who had been
      implanted with a Nucleus Mini22 device with a Nucleus Straight electrode between
      9 to 12 years ago suffered from severe FN stimulation. Electrode contacts had to
      be switched off so that they could only use 4, 11, 13, and 15 electrodes of their
      usual set of 22. The switch off resulted in deteriorating speech understanding
      over time. Therefore, all subjects were reimplanted with a Nucleus 24R device
      with a Contour electrode. Preoperatively, the threshold of FN stimulation was
      obtained on all electrodes subjectively. Intraoperatively, FN stimulation
      thresholds were measured objectively with both, the old and the new device and
      were compared. NRT and SRT thresholds were also obtained with the reimplanted
      device to assure effective electrical stimulation of the auditory nerve. RESULTS:
      In all four cases the postoperative fitting demonstrated no FN stimulation on all
      electrodes up to maximum comfortable level. The insertion of the Contour
      electrode array was complete in three cases, in one case the array could only be
      inserted partially similarly to the situation before the reimplantation. Speech
      perception tests showed a significant improvement in all subjects with the new
      device. CONCLUSION: Electrodes with modiolar facing contacts and perimodiolar
      position like the Nucleus Contour electrode reduce the possibility of facial
      nerve stimulation significantly due to more focused electrical stimulation.

PMID- 17006342
TI  - Hypertrophic cranial pachymeningitis associated with middle ear inflammation.
AB  - OBJECTIVE: To describe a series of patients with hypertrophic cranial
      pachymeningitis (HCP) associated with chronic middle ear inflammation. STUDY
      DESIGN: Retrospective case review. SETTING: University Hospital. PATIENTS: Six
      consecutive patients between the years 2000 and 2004 who had both middle ear
      disease and HCP (three men and three women; age range, 36-72 yr, mean age, 58.2
      yr). The diagnosis of HCP was made by the use of contrast-enhanced magnetic
      resonance imaging scans of the brain in all patients. INTERVENTIONS: Contrast
      enhanced magnetic resonance imaging (MRI) of the brain, dural biopsy, and
      otomicroscopic examination. MAIN OUTCOME MEASURE: Thickening and abnormal
      enhancement of the dura mater on the MRI of the brain. RESULTS: All of the six
      patients had chronic inflammatory middle ear diseases. Three patients had otitis
      media with effusion, two had chronic otitis media, and one had postoperative
      otorrhea. The most common presentations of HCP were headache and cranial nerve
      palsies. Cranial Nerves V and VIII were the most frequently involved. On contrast
      enhanced MRI examination of the brain, an enhancement of the dura mater was
      observed on the same side as the middle ear diseases in five of the six patients,
      whereas bilateral enhancement was observed in one patient. Corticosteroid therapy
      was effective for alleviating the symptoms in all six patients. CONCLUSION:
      Chronic middle ear inflammation might be involved in the pathogenesis of HCP,
      probably mediated by the venous return.

PMID- 17006343
TI  - Congenital cholesteatoma in a case of congenital aural atresia.
AB  - OBJECTIVE: A congenital cholesteatoma arising in the setting of congenital aural
      atresia is described. This represents the first case reported in the literature.
      STUDY DESIGN: Case report. SETTING: Tertiary otologic referral center, University
      of Virginia Health System, Charlottesville, Virginia. PATIENT: Eight-year-old
      patient with unilateral congenital aural atresia. INTERVENTIONS: Preoperative
      computer tomographic scanning and surgical atresia repair with removal of
      cholesteatoma. MAIN OUTCOME MEASURES: Recurrence of cholesteatoma; epithelialized
      ear canal; hearing improvement. RESULTS: A congenital cholesteatoma located
      medial to the ossicular mass in a child with congenital aural atresia was
      removed, with no evidence of recurrent disease at a revision operation 1 year
      later. Hearing was improved to a speech reception threshold of 25 dB. CONCLUSION:
      Congenital cholesteatoma can arise medial to the ossicular mass in congenital
      aural atresia. This finding lends support to the epidermoid rest theory for the
      cause of congenital cholesteatoma.

PMID- 17006344
TI  - Internal jugular vein thrombosis associated with acute mastoiditis in a pediatric
      age.
AB  - OBJECTIVE: To discuss the clinical aspects and management of internal jugular
      vein thrombosis associated with acute otitis media. STUDY DESIGN: Case reports
      and review of the literature. SETTING: University hospital, tertiary referral
      center. PATIENT: The authors describe two cases of internal jugular vein
      thrombosis, without sigmoid sinus thrombosis, secondary to acute otomastoiditis.
      INTERVENTION: Jugular vein thrombosis was diagnosed in both cases by observation
      of filling defects of the involved jugular bulb on contrast-enhanced computed
      tomography and confirmed by conventional magnetic resonance and magnetic
      resonance venography. RESULTS: Both patients recovered after recanalization of
      the vessel concomitant to anticoagulation and antibiotic treatment associated
      with a simple mastoidectomy. CONCLUSION: Internal jugular vein thrombosis may be
      a complication of acute otitis media, without involvement of the sigmoid sinus
      and with a starting point in the jugular bulb. Anticoagulation associated with
      antibiotic therapy can be considered a safe and effective treatment. Surgery
      should only be performed to eliminate the source of infection from the middle ear
      and mastoid.

PMID- 17006345
TI  - Caloric and rotatory chair test results in patients with Meniere's disease.
AB  - OBJECTIVES: To determine whether an association exists between the parameters of
      the caloric and rotatory chair tests in patients with unilateral Meniere's
      disease. METHODS: Patients with unilateral Meniere's disease (n = 100) were
      subjected to the caloric and the rotatory chair test (sinusoidal harmonic
      acceleration and impulsive tests) on the same day. Canal paresis and directional
      preponderance were assessed in the caloric test, and different variables were
      measured in the rotatory chair test based on the existence of abnormal parameters
      in the vestibulo-ocular reflex at two or three consecutive frequencies of those
      tested and on the time constant of the vestibulo-ocular reflex. STUDY DESIGN AND
      SETTING: A prospective study was conducted at a University hospital. RESULTS: An
      abnormal result in the caloric test was obtained from 73% of the patients. In the
      rotatory chair test, the most frequent abnormal findings involved increases in
      the normal phase lead at 2 consecutive frequencies tested (23%). There was a
      stronger association between an abnormal result in phase, gain, and/or symmetry
      at three adjacent frequencies and a pathological result in the caloric test.
      CONCLUSION: Very few of the criteria used to define the caloric and rotatory
      chair tests seem to be associated. This confirms previous knowledge that both
      tests examine vestibulo-ocular reflex by different ways. Only when vestibular
      dysfunction is severe enough (manifested by the finding of an abnormal result in
      at least three consecutive frequencies in the rotatory chair test), the caloric
      test is also found to be abnormal.

PMID- 17006346
TI  - Vestibular evoked myogenic potentials in acute acoustic trauma.
AB  - OBJECTIVES: Anatomical proximity of the saccule to the stapedial footplate points
      to the possibility of acoustic trauma associated with saccular dysfunction.
      Therefore, it was the authors' premise that abnormal vestibular evoked myogenic
      potential (VEMP) after acute acoustic trauma may be caused by saccular damage
      from very high intensity noise; consequently, irreversible hearing loss ensued.
      The aim of this study was to investigate the VEMP responses in those with acute
      acoustic trauma. STUDY DESIGN: A prospective study. SETTING: University hospital.
      PATIENTS: Twenty patients (29 ears) without previous ear disorders diagnosed as
      acute acoustic trauma were enrolled in this study. MAIN OUTCOME MEASURES: Before
      treatment, each patient underwent pure tone audiometry and caloric and VEMP
      tests. Correlations between the hearing outcome and mean hearing level, sources
      of noise, caloric responses, or VEMP results were investigated. RESULTS: After 3
      months of medication, complete recovery was achieved in 4 ears and hearing
      improvement in 4 ears, whereas hearing in 21 ears (72%) remained unchanged.
      Eighteen ears presenting normal VEMPs revealed hearing improvement in eight ears
      (44%) and unchanged hearing in ten ears (56%). However, hearing loss remained
      unchanged in all 11 ears (100%) with absent or delayed VEMPs, exhibiting a
      significant relationship between VEMP results and hearing outcome. Thus, VEMP
      test can predict the hearing outcome after acute acoustic trauma with a
      sensitivity of 44% and a specificity of 100%. CONCLUSION: The greater the noise
      intensity, the severer damage on the cochlea and saccule is shown. Absent or
      delayed VEMPs in ears after acute acoustic trauma may indicate poor prognosis
      with respect to hearing improvement, whereas normal VEMP is not a powerful
      indicator for expectation of hearing improvement.

PMID- 17006347
TI  - Volumetrical measurements in vestibular schwannoma, the influence of slice
      thickness and patient's repositioning.
AB  - OBJECTIVE: Conservative treatment in vestibular schwannomas is mainly dependent
      on optimal tumor size determination. The first objective of this study was to
      establish interobserver and intraobserver variability and the accuracy and
      reproducibility of three different measurement methods: one bidimensional and two
      volumetrical. The second objective was to evaluate the influence of the use of
      different magnetic resonance imaging (MRI) slice thickness and the influence of
      patient's repositioning on the measurements' outcome. STUDY DESIGN: Two
      consecutive studies have been prospectively performed, both mainly concerning
      volumetrical measurements. SETTING: Both studies were performed in a tertiary
      academic, multidisciplinary center. PATIENTS: In the first study, 19 patients
      were included between March 1996 and May 2002, with a total of 52 scans. The
      second study comprised 14 patients. All patients in the first study had at least
      two MRI examinations performed according to a standard protocol (T1-weighted
      gadolinium-enhanced, slice thickness of 3 mm, and interslice gap of 0.3 mm). The
      population in the second study underwent a conservative wait and scan (W&S)
      treatment. METHODS: Both studies are discussed separately. In the first study,
      all scans were measured by four investigators, two of whom performed the
      measurements twice using three different methods. The first method concerns a
      manually performed bidimensional surface measurement along the petrous pyramid.
      The second method concerns a semiautomatic volumetrical measurement on a
      computer, relying on contour detection, and the last method concerns a fully
      automatic volume reconstruction also performed on a computer using different gray
      shade scales. All 14 patients included in the second study underwent three
      magnetic examinations. Three different T1-weighted gadolinium-enhanced sequences
      were used: the first using a slice thickness of 1 mm, the second again with 1-mm
      slice thickness but after having repositioned the patient. In the third sequence,
      a slice thickness of 3 mm was used. All scans were measured by two investigators
      using the three different methods, as described previously. RESULTS: The manual
      surface method shows large intraobserver variability, and its reproducibility is
      significantly lower compared with volume measurements. Because of a relatively
      large systematic error in small tumors, sensitivity of growth detection is low.
      Both volumetrical methods are hardly interobserver- and intraobserver-dependent,
      and the gray shade method turned out to be the most accurate. Radiologic
      progression is only significant at a volume increase of at least 50%. The
      influence of patient repositioning is negligible, whereas the use of 1-mm slice
      thickness seems to be superior to a 3-mm slice thickness. CONCLUSION: The
      volumetrical gray shade method is the most accurate method to detect early tumor
      progression. As tumor increase of at least 50% is needed to be able to speak of
      statistically significant tumor growth, the absence of radiologic progression
      does not mean that there is no tumor growth. Repositioning of the patient has no
      influence on the measurements' outcome, whereas for optimal magnetic resonance
      imaging examinations, a 1-mm slice thickness protocol seems to be superior.

PMID- 17006348
TI  - Auditory function in patients with surgically treated superior semicircular canal
      dehiscence.
AB  - OBJECTIVE: To characterize preoperative and postoperative audiologic findings in
      patients with superior semicircular canal dehiscence syndrome. STUDY DESIGN:
      Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Patients
      with documented superior semicircular canal dehiscence syndrome (according to
      history, vestibular testing, and high-resolution computed tomography imaging) who
      underwent surgical repair of their dehiscence. INTERVENTION: Middle fossa
      craniotomy for superior semicircular canal plugging and/or resurfacing. MAIN
      OUTCOME MEASURES: Audiologic testing both before and after surgery with pure-tone
      threshold measurements of air and bone conduction. RESULTS: Twenty-nine subjects
      underwent surgical repair of superior semicircular canal dehiscence. Overall,
      there were no statistically significant differences by paired t test in hearing
      before or after surgery, in either air-conduction or bone-conduction thresholds,
      for 19 patients that had no previous surgical history. At least partial closure
      of air-bone gap was achieved in five patients. One patient with previous stapes
      surgery had significantly worse hearing both before and after canal repair
      compared with those without previous surgery. Two patients who had undergone
      previous middle fossa surgery with incomplete resolution of symptoms developed
      sensorineural hearing loss after revision surgery. Previous middle-ear
      exploration and tympanostomy tube placement did not seem to affect audiologic
      outcomes. Surgical hearing results did not differ according to method of canal
      repair (plugging versus resurfacing). CONCLUSION: Primary middle fossa repair of
      superior semicircular canal dehiscence is not associated with sensorineural
      hearing loss and, in some cases, can lead to normalization of conductive hearing
      loss. Revision middle fossa repair or previous stapes surgery may be associated
      with postoperative sensorineural hearing loss.

PMID- 17006349
TI  - Chondrosarcoma of the skull base: long-term follow-up.
AB  - OBJECTIVE: Chondrosarcoma of the skull base is an uncommon neoplasm comprising
      0.15% of all intracranial tumors and 6% of skull base neoplasms. The outcome of
      treatment is difficult to assess because the slow growth rate means that there is
      a long interval before detecting the recurrence. We describe the use of lateral
      skull base techniques for these lesions and examine the long-term outcomes. The
      pathological features, radiological findings, and radiotherapy options are also
      discussed. STUDY DESIGN: Retrospective case review with current follow-up where
      possible. SETTING: Tertiary referral neurotologic private practice. PATIENTS:
      Eight patients with histologically confirmed skull base chondrosarcoma operated
      on since 1979. At the time of the surgery, the five women and three men ranged in
      age from 31 to 63 years, with a mean of 42.9 years. The follow-up ranged from 9
      months to 25 years and 5 months. INTERVENTIONS: All patients underwent surgical
      removal; the earliest patient underwent surgical removal via transcochlear and
      retrosigmoid approaches, and seven via an infratemporal fossa approach, with or
      without exenteration of the otic capsule. MAIN OUTCOME MEASURES: Number of
      patients with residual and recurrent tumors. RESULTS: In the patient who
      underwent surgery via the transcochlear approach, recurrence was noted within 3
      months, and new exploration using the retrosigmoid approach was performed for the
      removal of the recurrent lesion. This patient showed no signs of recurrence for
      25 years since last surgery. Of the seven patients who underwent surgery via the
      infratemporal fossa approach, one had residual tumor found at 1 year, but
      remained alive and well for 21 years after the surgery. The other six had gross
      total resection and showed no signs of recurrence at the last known follow-up.
      One patient died as a result of an unrelated cause 18 years after surgery for the
      chondrosarcoma. CONCLUSION: The gross total resection of these lesions is
      possible because of the evolution of lateral skull base techniques and can be
      routinely accomplished with the infratemporal fossa approach. The improved
      exposure afforded by this approach seems to have resulted in more complete
      extirpation of the tumor and a decrease in the recurrence rate.

PMID- 17006350
TI  - Serous otitis media revealing temporal en plaque meningioma.
AB  - OBJECTIVES: To present a series of temporal en plaque meningiomas involving the
      middle ear or mastoid, whose main symptoms suggested a serous otitis media. STUDY
      DESIGN AND SETTINGS: Multicentric retrospective study reviewing clinical records
      originating from eight tertiary referral centers. MATERIALS AND METHODS: The
      clinical records of 10 patients presenting with signs and symptoms suggesting
      serous otitis media and whose neuroimaging studies revealed a temporal en plaque
      meningioma involving the middle ear or mastoid are reported. RESULTS: All the
      patients were women, ranging from 49 to 71 years old. The delay between the onset
      of symptoms and the diagnosis of meningioma varied from 1 to 10 years. All the
      patients underwent various procedures usually applied for the treatment of serous
      otitis media, which failed in all the cases, particularly ventilating tube
      placement, which was followed by severe episodes of discharge. In all cases, the
      computed tomographic scans showed three imaging signs: soft tissue mass filling
      the middle ear or mastoid, hyperostosis of the petrous bone, and hairy aspect of
      the intracranial margins of the affected bone. This imaging triad must alert the
      otologist of the possibility of intracranial meningioma. Magnetic resonance
      imaging was the method of choice to assess the diagnosis of intracranial
      meningioma involving the middle ear or mastoid. When analyzing management
      options, it appeared that conventional middle ear procedures were inefficient.
      CONCLUSION: Temporal en plaque meningioma involving the middle ear or mastoid can
      mimic a serous otitis media. A computed tomographic scan is recommended for cases
      of atypical or prolonged unilateral serous otitis media to investigate indirect
      signs of a meningioma, which has to be confirmed with magnetic resonance imaging.

PMID- 17006351
TI  - Circumferential petrosectomy for petrous apicitis and cranial base osteomyelitis.
AB  - OBJECTIVE: Petrous apicitis and cranial base osteomyelitis are life-threatening
      conditions. A surgical management may be necessary in cases that progress, in
      conditions that fail to improve with medical treatment, or in cases with
      impending complications. In this study, we describe a technique to remove the
      maximum amount of infected temporal bone while preserving the integrity of the
      peripheral auditory pathway and facial nerve. STUDY DESIGN: Retrospective study.
      SETTING: Tertiary referral hospital. PATIENTS: Five patients with impending
      complications, whose disease progressed or whose conditions failed to improve
      while on culture-directed antibiotics underwent circumferential petrosectomy.
      INTERVENTIONS: The circumferential petrosectomy removes most of the temporal bone
      around the external, middle, and inner ear. A combined retrolabyrinthine-apical
      petrosectomy is performed in conjunction with the fallopian bridge technique
      using a transmastoid and middle cranial fossa approach. A split temporalis muscle
      flap is used to bring vascularized tissue to the mastoid, jugular foramen, and
      petrous apex. MAIN OUTCOME MEASURES: Disease resolution, change in hearing or
      facial nerve function, complications. RESULTS: Each of the five patients had
      modifications to the procedure tailored to their disease extent: three had
      disease primarily involving the petrous apex and two had disease adjacent to the
      jugular foramen. Additional cultures of the infected bone were obtained during
      surgery. A culture-directed antibiotic therapy (duration, 6-10 weeks) was
      administered after surgery, which resulted in the complete resolution of the
      disease and the associated symptoms in all five patients. No patient experienced
      hearing loss or facial nerve dysfunction as a result of the surgery within at
      least 1 year of follow-up in four of the five patients in this series.
      CONCLUSION: The circumferential petrosectomy is a potential treatment option when
      medical treatment fails in patients with petrositis or cranial base
      osteomyelitis. It permits maximal temporal bone debridement while preserving
      hearing and facial nerve integrity in these life-threatening disease processes.

PMID- 17006352
TI  - Disseminated histoplasmosis presenting as a unilateral cranial nerve VIII mass: a
      case report.
AB  - OBJECTIVE: To report a unique presentation of disseminated histoplasmosis. STUDY
      DESIGN: Case report. SETTING: University hospital, tertiary referral center.
      PATIENT: Our patient presented with vertigo, tinnitus, and unilateral hearing
      loss, and was initially found to have a 5-mm enhancing left internal auditory
      canal mass, as revealed by a magnetic resonance imaging (MRI) scan. Subsequently,
      the patient developed multiple focal neurologic deficits. INTERVENTIONS: Magnetic
      resonance imaging and treatment with intravenously administered amphotericin B,
      with subsequent oral administration of itraconazole. MAIN OUTCOME MEASURES:
      Clinical presentation and imaging findings of Histoplasmosis involving the
      cranial nerve VIII. RESULTS: A subsequent MRI scan revealed enlargement of the
      initial lesion and multiple parenchymal lesions. Further workup revealed a
      pulmonary lesion; the diagnosis of disseminated histoplasmosis was made on the
      basis of bronchoalveolar lavage culture. CONCLUSION: Infectious processes,
      including disseminated histoplasmosis, should be considered in the differential
      of internal auditory canal masses, especially in the setting of rapid progression
      of symptoms.

PMID- 17006353
TI  - A novel method in predicting immediate postoperative facial nerve function post
      acoustic neuroma excision.
AB  - To determine whether the percentage calculated by dividing the amplitude of
      postexcision direct facial nerve stimulus responses (at pontomedullary junction)
      by the amplitude of distal ipsilateral transcutaneous (stylomastoid region)
      maximal stimulus responses and response amplitude progression by increasing
      stimulus intensities have predictive value for determining normal or near-normal
      (House-Brackmann Grade 1 or 2) immediate postoperative facial nerve function.
      STUDY DESIGN: Intraoperative recordings of three muscle groups: 1) frontalis, 2)
      orbicularis oculi, and 3) orbicularis oris. Postexcision direct facial nerve
      stimulation at the pontomedullary junction and transcutaneous maximal facial
      nerve stimulation at the ipsilateral stylomastoid region and their associated
      response amplitudes were recorded. SETTING: Tertiary referral center. PATIENTS
      AND METHODS: Patients who underwent acoustic neuroma surgery from January 2004 to
      March 2006 with intraoperative facial nerve monitoring and an intact facial nerve
      after tumor excision were included. Recordings were available for 38 patients.
      RESULTS: With a stimulus intensity of 0.3 mA at the root exit zone, there was an
      81% positive predictive value in patients that exhibited a compound action
      potential of greater than 20% of maximum (sensitivity, 81%). This increased to
      93% when the compound action potential was greater than 50% of maximum. When the
      amplitude increase was greater than 5 microV, there was a 77% positive predictive
      value (sensitivity, 87%). CONCLUSION: The percentage of the response amplitude of
      direct facial nerve stimulation at the pontomedullary junction when compared with
      the maximum response amplitude of ipsilateral transcutaneous stimulation at the
      stylomastoid foramen is a good predictor of normal to near-normal immediate
      postoperative facial nerve function. Progression of amplitude response also seems
      to be a good predictor of normal to near-normal immediate postoperative facial
      nerve function.

PMID- 17006354
TI  - Quantification of facial motion for objective evaluation using a high-speed three
      dimensional face measurement system--a pilot study.
AB  - OBJECTIVE: To estimate asymmetry in normal and pathological facial functions
      using an established computer generated objective evaluation technique. METHODS:
      Analysis was performed on three-dimensional (3-D) data captured using a specially
      designed 3-D face shape measurement system. Six healthy volunteers and six
      patients with Bell's palsy were analyzed for forced eye closure and grinning
      actions. The asymmetry was computed at locations that had the greatest effect in
      each action on both the left and right sides of the face, in reference to a
      relaxed condition. The patients' data were captured and analyzed repeatedly for a
      period of three days for an average interval of four weeks, and the results were
      compared with the Yanagihara scale. RESULTS: The control set of a normal sample
      exhibited a low standard deviation and a high correlation coefficient in both
      facial actions, and this contributed to a robust evaluation. The patients showed
      a higher standard deviation than the healthy subjects because of the larger
      degree of scatter of the data points in their respective data distributions.
      During the three clinical examinations, our proposed quantification method
      produced a continuous grading scheme, as opposed to the discrete scheme of the
      House-Brackmann grading. CONCLUSION: Our proposed system shows advantages over
      the existing methods in that it does not rely on reference points nor does it use
      markers to analyze facial deformation. In addition, our estimations are very
      robust and accurate because our approach directly evaluates 3-D spatial
      variations in normal and pathological facial functions.

PMID- 17006355
TI  - Grading facial nerve function: why a new grading system, the MoReSS, should be
      proposed.
AB  - OBJECTIVE: To compare the interobserver variability of a new grading system to
      the currently recommended House-Brackmann Grading Scale. STUDY DESIGN:
      Prospective case-control study. SETTING: Tertiary referral center. PATIENTS: All
      patients with a facial nerve paresis/paralysis (whatever the cause).
      INTERVENTION: All patients were evaluated for their facial nerve function by
      three observers, independently, using both the new system and the House-Brackmann
      Grading Scale. MAIN OUTCOME MEASURE: The level of agreement between the three
      observers using both scales. RESULTS: With the movement, rest, secondary defects,
      and subjective scoring grading scale, a higher percentage of agreement between
      the observers was noticed than with the House-Brackmann Grading Scale.
      CONCLUSION: The movement, rest, secondary defects, and subjective scoring grading
      system is more useful for grading facial nerve dysfunction in clinical practice
      than the House-Brackmann Grading Scale.

PMID- 17006356
TI  - Stability of benefits of mime therapy in sequelae of facial nerve paresis during
      a 1-year period.
AB  - OBJECTIVE: To assess the stability of benefits of mime therapy, a modality of
      physiotherapy for patients with facial nerve paresis, during a period of 1 year.
      STUDY DESIGN: A prospective follow-up build on a randomized clinical trial in
      which a treatment group is compared with a control group. SETTING: Physiotherapy
      outpatient department. PATIENTS: Forty-eight patients with a history of a facial
      nerve paresis of 9 months or more. INTERVENTION: Mime therapy. METHOD: Sequelae
      of facial nerve paresis were measured using the same measurement instruments as
      in the randomized clinical trial--the Sunnybrook and the House-Brackmann (HB)
      Facial Grading Systems, the lip length and pout indices, a stiffness scale, and
      the Facial Disability Index. Stability of outcome level and of interpatient
      differences is analyzed. RESULTS: Of the 46 patients who completed the follow
      ups, repeated-measures analyses of covariance revealed no significant differences
      in the average scores nor significant trends of the posttherapy measurements,
      except for the pout index and the Facial Disability Index-social. For six
      sequelae (except HB), 95% of patient-sequel combinations showed immediate
      improvement after mime therapy, for HB grades this was 74%. Where sequelae
      improved, the posttherapy individual courses (T2-T3-T4) showed, also for HB, in
      majority absence of deterioration; benefits obtained were stable. CONCLUSION:
      Mime therapy is effective in patients with facial nerve paresis and benefits are
      stable 1 year after therapy.

PMID- 17006357
TI  - Infectious skull base osteomyelitis--still a life-threatening disease.

PMID- 17006359
TI  - Peritoneal lavage with activated protein C alters compartmentalized coagulation
      and fibrinolysis and improves survival in polymicrobial peritonitis.
AB  - OBJECTIVE: During peritonitis, intra-abdominal fibrin entraps bacteria and
      hampers their elimination. Systemic administration of anticoagulant activated
      protein C improves survival in patients with severe sepsis, but its precise mode
      of action is unclear. This study in polymicrobial peritonitis assessed the
      effects of local activated protein C administration in peritoneal lavage fluid on
      coagulation, fibrinolysis, and survival. DESIGN: Prospective, randomized study.
      SETTING: University-based research laboratory. SUBJECTS: C57BL/6 mice.
      INTERVENTIONS: Twenty-four hours after induction of peritonitis by cecal ligation
      and puncture, mice underwent peritoneal lavage with activated protein C (1.0
      microg/mL) or saline. Peritoneal lavage fluid, blood, and lungs were sampled
      after 24, 48, or 72 hrs (n = 8/group/time point). For survival analysis, maximum
      observation was 96 hrs (n = 22/group). Clotting time, tissue factor expression,
      thrombin-antithrombin complexes, fibrin degradation products (D-dimers),
      plasminogen activator, and plasminogen activator inhibitor were used to assess
      coagulation and fibrinolysis responses. MEASUREMENTS AND MAIN RESULTS: Activated
      protein C lavage reduced abdominal bacterial load, abdominal and pulmonary
      clotting times, D-dimers (p < .05 vs. saline), pulmonary tissue factor
      expression, and fibrin depositions, without clear effects on systemic thrombin
      generation. Activated protein C lavage decreased plasma and abdominal tissue
      plasminogen activator levels with increased inhibitor plasminogen activator
      inhibitor-1 levels (p < .05) but had reverse effects on pulmonary fibrinolysis.
      Survival improved from 55% (saline) to 80% after intra-abdominal activated
      protein C administration (p = .03). CONCLUSIONS: Peritoneal lavage with activated
      protein C may rebalance coagulation and fibrinolysis within compartments and
      improve survival in polymicrobial peritonitis.

PMID- 17006360
TI  - Open lung ventilation preserves the response to delayed surfactant treatment in
      surfactant-deficient newborn piglets.
AB  - OBJECTIVE: Delayed surfactant treatment (>2 hrs after birth) is less effective
      than early treatment in conventionally ventilated preterm infants with
      respiratory distress syndrome. The objective of this study was to evaluate if
      this time-dependent efficacy of surfactant treatment is also present during open
      lung ventilation. DESIGN: Prospective, randomized controlled animal study.
      SETTING: University-affiliated research laboratory. SUBJECTS: Thirty-eight
      newborn piglets. INTERVENTIONS: Following repeated whole-lung lavage, animals
      were randomly allocated to conventional positive pressure ventilation (PPVCON)
      using a positive end-expiratory pressure (PEEP) of 5 cm H2O and a tidal volume of
      7 mL/kg or open lung positive pressure ventilation (PPVOLV). During PPVOLV,
      collapsed alveoli were actively recruited and thereafter stabilized with
      sufficient PEEP. Within each ventilation group, animals received surfactant (25
      mg/kg) either after 2 hrs (PPVCON-2 and PPVOLV-2) or after 4 hrs (PPVCON-4 and
      PPVOLV-4) of ventilation. A control group received surfactant immediately after
      lung lavage. Following surfactant administration, all animals were conventionally
      ventilated for an additional 2 hrs. MEASUREMENTS AND MAIN RESULTS: Two hours
      after surfactant treatment, both oxygenation and lung mechanics showed a clear
      deterioration in the PPVCON-4 group compared with PPVCON-2 and the control group.
      However, this deterioration of the surfactant response over time was not observed
      during PPVOLV. Analysis of the bronchoalveolar lavage fluid obtained at the end
      of the experiment showed that the protein concentration and the conversion of
      large to small aggregate surfactant was significantly higher in the PPVCON-4
      group compared with the PPVCON-2 group while comparable in both PPVOLV groups. In
      addition, interleukin-8 and myeloperoxidase levels tended to be higher in the
      PPVCON-4 group compared with the PPVOLV-4 group. CONCLUSIONS: In contrast to
      conventional ventilation, open lung ventilation preserves the response to delayed
      surfactant treatment in surfactant-deficient newborn piglets. This sustained
      response is accompanied by an attenuation of secondary lung injury.

PMID- 17006361
TI  - Factors affecting survival of uncemented total hip arthroplasty in patients 50
      years or younger.
AB  - Providing a long-lasting total hip arthroplasty for patients younger than 50
      years remains one of the greatest challenges for modern arthroplasty surgery. We
      retrospectively reviewed 221 patients younger than 50 years who underwent 299
      uncemented total hip arthroplasties from 1983 to 2000. We assessed 5- to 15-year
      survival with revision as the endpoint. Femoral stem survival was 99.3% (range,
      98.4-100%), 98.9% (range, 97.7-100%), and 96.8% (92.5-100%) at 5, 10, and 15
      years, respectively. Including all component designs acetabular survival was
      98.7% (range, 97.4-100%), 84.6% (78.8-90.4%), and 52.5% (40.7-64.3%) at 5, 10,
      and 15 years, respectively. Overall survival was 46.8% (33.5-58.1%) at 15 years.
      Total hip arthroplasties performed for hip dysplasia had lower 10-year and 15
      year survival. Zirconium-on-polyethylene articulations had lower acetabular
      revision rates compared with cobalt-chrome-on-polyethylene. Sixty-nine revisions
      were performed, most commonly for polyethylene wear. Uncemented femoral stems
      resulted in 90% survival at 15 years followup in patients younger than 50 years
      at index operation. Contemporary bearing surfaces in association with such stems
      may provide long-lasting total hip arthroplasties, even in young, active
      patients.

PMID- 17006362
TI  - Missed opportunities in patients with osteoporosis and distal radius fractures.
AB  - Low-energy wrist (distal radius) fractures are hallmarks of osteoporosis. Prompt
      diagnosis and treatment of osteoporosis reduce refracture rates. We
      retrospectively determined the type and frequency of osteoporosis-related
      interventions rendered to patients 50 years and older in the year after a wrist
      fragility fracture. In addition, we compared the rates of intervention between
      men and women. Data were collected from the computerized medical record of one
      military healthcare system. We identified 111 patients who sustained wrist
      fragility fractures between July and December 2002. Endocrinology referrals, dual
      energy xray absorptiometry scans, and osteoporosis medication prescriptions in
      the year after their fracture were recorded. Overall, 28 patients (25%) were
      referred to endocrinology, 22 patients (20%) had a dual-energy xray
      absorptiometry scan, 33 patients (30%) were prescribed an approved medication for
      treatment of osteoporosis, and 52 patients (47%) were prescribed one of these
      medications and/or vitamin D and calcium. Sixty percent of patients received at
      least one intervention. All diagnostic and medical interventions were more likely
      ordered for women than men. Orthopaedic surgeons continue to miss opportunities
      to initiate diagnostic and therapeutic interventions for patients, especially
      men, presenting with fragility fractures.

PMID- 17006363
TI  - All-polyethylene and metal-backed tibias have similar outcomes at 10 years: a
      randomized level I [corrected] evidence study.
AB  - The advantages of a monoblock design and lower cost have generated renewed
      interest in all-polyethylene tibial components for total knee arthroplasty (TKA).
      We hypothesized an all-polyethylene design would function equivalently to a metal
      backed modular design at lower cost and at long-term followup. We report the 8-
      to 12-year followup of our earlier reported prospective randomized comparison of
      a modern congruent all-polyethylene tibial component with a modular metal-backed
      tibial component of the same design. The mean age of the patients was 69 years
      and 92% were diagnosed with osteoarthritis. Of 290 patients (316 total knee
      arthroplasties) enrolled, 120 patients died, 22 had revision surgery, and one was
      lost to followup. We followed the remaining 147 patients (167 TKAs: 97 all
      polyethylene/70 metal-backed) clinically and radiographically. There were no
      differences in knee function (Knee Society clinical score, range of motion,
      stability) or radiographic parameters between the groups. Of the 22 revisions,
      only three were performed for tibial aseptic loosening (three metal-backed). Ten
      year survivorship of the all-polyethylene tibial component was 91.6% with
      revision for any reason and 100% for aseptic loosening. The metal-backed tibial
      component survivorship was 88.9% with revision for any reason and 94.3% for
      aseptic loosening. The contemporary all-polyethylene tibial component functioned
      equivalently to its monoblock counterpart and was less costly.

PMID- 17006364
TI  - Functional pelvic orientation measured from lateral standing and sitting
      radiographs.
AB  - We prospectively obtained preoperative and 3-month postoperative lateral pelvic
      radiographs in the standing and sitting positions from 84 patients who underwent
      total hip arthroplasty. We measured pelvic orientation (flexion extension) using
      the anterior pelvic plane as defined by the anterior superior iliac spines and
      pubic tubercles as references. There was a trend towards upright pelvic alignment
      when standing, with a mean anterior pelvic plane angle of 1.2 degrees (range, -22
      degrees - +27 degrees). In the sitting position the pelvis tended to extend
      posteriorly, with a mean anterior pelvic plane angle of -36.2 degrees (range, -64
      degrees - +4 degrees). There was a wide variation in the arc of pelvic flexion
      extension as patients moved from standing to sitting, with are of pelvic motion
      in some patients as mobile as 70 degrees and in others as stiff as 5 degrees.
      There was no significant variation between males and females or between
      preoperative and postoperative pelvic flexion extension. There were substantial
      variations in pelvic orientation when comparing standing and sitting for an
      individual patient and between different patients. This variation can be
      unpredictable, and may influence implant alignment and stability after total hip
      arthroplasty.

PMID- 17006365
TI  - Multimodal prophylaxis for THA with mechanical compression.
AB  - We used mechanical thromboembolism prophylaxis using intraoperative thigh-calf
      pneumatic compression and other measures in 1032 consecutive primary and revision
      total hip arthroplasties. No chemical prophylactic measures were used until after
      duplex ultrasonography was performed by experienced technologists before
      discharge. Asymptomatic proximal thrombi were treated with low molecular weight
      heparin and warfarin, whereas those patients with a negative scan or distal
      thrombi only were advised to take aspirin 325 mg twice a day for 6 weeks.
      Regional anesthesia was used in 95% of the arthroplasties. Using this protocol,
      the 30-day mortality was 0.3%. There was one autopsy-proven fatal pulmonary
      embolism (0.09%). One other patient died suddenly with cardiac arrest after
      abdominal pain and vomiting, but no autopsy was performed. Symptomatic pulmonary
      embolism occurred in seven patients (0.7%), four occurring early and three late.
      Only one of these seven patients had a positive duplex scan. Deep vein thrombosis
      occurred in 41 patients (3.9%) and 35 remained asymptomatic. We observed no
      association between type of surgery (primary or revision), age, gender or
      preoperative diagnosis and pulmonary embolism or deep vein thrombosis. The data
      confirm the efficacy of a multimodal protocol with thigh-calf mechanical
      prophylaxis for almost all patients undergoing primary or revision total hip
      arthroplasty.

PMID- 17006366
TI  - Muscle damage during MIS total hip arthroplasty: Smith-Petersen versus posterior
      approach.
AB  - Decreased muscle damage is a reported benefit of minimally invasive surgical
      (MIS) approaches in total hip arthroplasty (THA). We compared the extent and
      location of muscle damage during THA using the MIS anterior Smith-Petersen and
      MIS posterior surgical approaches. THA was performed in six human cadavers (12
      hips). One hip was assigned to the Smith-Petersen approach and the contralateral
      hip to the posterior approach. Muscle damage was graded with a technique of
      visual inspection to calculate a proportion of surface area damage. Less damage
      occurred in the gluteus minimus muscles and minimus tendon with the Smith
      Petersen approach. A mean of 8% of the minimus muscle was damaged via the Smith
      Petersen approach, compared to 18% via the posterior approach. The tensor fascia
      latae muscle was damaged (mean of 31%), as well as direct head of the rectus
      femoris (mean 12%) during the Smith-Petersen approach. The piriformis or
      conjoined tendon was transected in 50% of the anterior approaches to mobilize the
      femur. The posterior approach involved intentional detachment of the piriformis
      and conjoined tendon and measurable damage to the abductor muscles and gluteus
      minimus tendon in each specimen. Clinical outcome studies and gait analysis are
      necessary to ascertain the functional implications of these findings.

PMID- 17006367
TI  - Patients preferred a mini-posterior THA to a contralateral two-incision THA.
AB  - The two-incision total hip arthroplasty (THA) technique has been touted as
      offering substantially faster recovery than other methods of THA, but direct
      comparison studies in similar groups of patients have not been done. We sought to
      determine if there was a difference in the early functional outcome after a two
      incision THA compared to a mini-posterior THA as measured by the time to reach
      defined milestones of daily activity. We also evaluated which procedure the
      patients preferred. Twenty-six patients underwent staged bilateral total hip
      arthroplasties with a two-incision minimally invasive THA on one hip and a mini
      posterior THA on the contralateral hip. The same comprehensive anesthesia and
      rapid rehabilitation protocol was used after each operation. Patients were
      reviewed retrospectively a minimum of 6 months after the second total hip
      arthroplasty. There were no differences in the time to discontinue ambulatory
      aids, return to driving, climb stairs, return to work, or walk 1/2 mile. Sixteen
      of 26 patients preferred the mini-posterior total hip arthroplasty and two
      patients had no preference. The added surgical technical difficulty of the two
      incision minimally invasive total hip arthroplasty was not rewarded with an
      earlier return to functional activities and more patients preferred their mini
      posterior total hip arthroplasty.

PMID- 17006368
TI  - The potential for bone loss in acetabular structures following THA.
AB  - Attempts to preserve periacetabular bone stock following total hip replacement
      have largely ignored the potential for stress shielding in the acetabulum. We
      sought to quantify the change in stress distribution in acetabular bone with
      components of varying material stiffness by developing a high-resolution 3-D
      finite element model from CT scans of a young female donor. Periprosthetic bone
      stresses and strains on the left pelvis were compared with hemispherical cups of
      various material properties and with a horseshoe shaped polymeric design
      described in the recent literature. We observed unphysiologic periacetabular bone
      stress and strain fields for all designs tested. For hemispherical components,
      reduction of the acetabular shell material modulus caused modest changes in bone
      stress compared to the changes in implant geometry. The horseshoe shaped cup more
      effectively loaded the acetabular structures than the hemispherical design. Our
      results suggest stress and strain fields in pelvic structures after introduction
      of hemispherical acetabular components predict inevitable bone adaptation that
      can not be resolved by changes in implant material properties alone. Radical
      changes in implant design may be necessary for long-term maintenance of
      supporting structures in the reconstructed acetabulum.

PMID- 17006369
TI  - Metal-on-metal hip resurfacing compares favorably with THA at 2 years followup.
AB  - Metal-on-metal total hip resurfacing is a bone-conserving reconstructive option
      for patients with advanced articular damage. While intended to address several
      problems with conventional THA, the safety and efficacy is not well established.
      We therefore retrospectively compared the outcomes of 52 patients (57 hips) with
      resurfacing arthroplasty to 84 patients (93 hips) with cementless primary THAs.
      The patients had a minimum 2-year followup (mean 3 years). The patients with
      resurfacing arthroplasty had a mean age of 47 years (range, 22-64) while those
      with cementless primary THA had a mean age of 57 years (range, 17-92). After
      controlling for age, gender, and preoperative differences, the total Harris Hip
      Scores (HHS), function scores, and pain scores were similar between the two
      groups. However, the resurfacing group had higher activity scores (14 versus 13,
      p < 0.001) and range of motion (ROM) scores (5.0 versus 4.8, p < 0.001). The
      complication rates (5.3% for resurfacing versus 14.0% for THA) and reoperation
      rates (3.5% for resurfacing versus 4.3% for THA) were similar. The total hip
      arthroplasty and metal-on-metal resurfacing groups both showed improvement in
      HHS, pain, activity, and ROM and had similar early complication and reoperation
      rates.

PMID- 17006370
TI  - Dislocation of primary total hip arthroplasty with 36 and 40-mm femoral heads.
AB  - Some authors suggest the use of larger (36 and 40 mm) femoral heads against
      highly cross-linked polyethylene acetabular liners will reduce the prevalence of
      early dislocation after primary total hip arthroplasty (THA). We prospectively
      followed 61 consecutive patients at high risk for dislocation to determine the
      prevalence of early dislocation after primary THA with 36 and 40 mm femoral
      heads. We established specific indications for the use of these larger heads in
      primary arthroplasty. There were 65 hips in 61 patients with a minimum followup
      of 1 year (mean 2 years, range 1-4 years). There were 55 36 mm heads and 10 40 mm
      heads. All arthroplasties were performed by the posterior approach with capsular
      repair. The prevalence of early dislocation was 4.6% (3 of 65). There was one
      patient with an anterior dislocation and two with posterior dislocation. No
      patient underwent reoperation for dislocation. There was no dislocation in the 10
      hips that had a 40 mm head. We identified no complications related to the larger
      femoral heads. The use of larger femoral heads did not notably reduce the
      prevalence of early dislocation after primary THA in high risk patients compared
      to historical controls.

PMID- 17006371
TI  - Improved results using extensively coated THA stems at minimum 5-year followup.
AB  - The Prodigy femoral component was extensively coated along its entire length,
      except for a smooth bullet-shaped distal tip. At a minimum 5 year followup we
      compared the results of that stem to those of a proximally coated first
      generation femoral component at comparable followup to address the question of
      which design performed better. For the extensively coated cohort, 86 patients
      (100 hips) underwent total hip arthroplasty by a single surgeon. At final
      followup, no patients were lost to followup and no hips were revised for aseptic
      loosening. Clinically, 3% of patients reported thigh pain (versus 15% in the
      proximally coated group). Radiographically, all hips had evidence of bone
      ingrowth (versus 94% in the PCA group). As expected with an extensively coated
      device there were fewer radiolucencies around the lower half of the prosthesis as
      well as less distal femoral lysis compared to the proximally coated stem.

PMID- 17006372
TI  - Failure mechanisms of total hip resurfacing: implications for the present.
AB  - In the past decade, there has been a renewed interest in hip resurfacing due to
      recent design improvements. It is unclear whether the recent improvements have
      accounted for all of the previous failure mechanisms. We determined the long-term
      performance of hip resurfacing, while paying special attention to the mechanisms
      of failure. We retrospectively reviewed 62 patients (65 hips) who had Indiana
      conservative hip prostheses implanted between 1977 and 1981. Forty-one of 62
      joints had failed, representing a failure rate of 66%. The time to failure
      averaged 9.7 years with a range of 6 months to 21.5 years. There were 23 femoral
      failures (37%). Eleven were caused by femoral fracture, and 12 were caused by
      femoral loosening. All late femoral failures (greater than 10 years
      postoperatively) showed narrowing of the femoral neck secondary to stress
      shielding. There were 18 acetabular failures (29%) with 10 failing secondary to
      polyethylene wear and eight failing secondary to acetabular loosening. Failure of
      the Indiana conservative hip prosthesis continues over time related to femoral
      and acetabular failure mechanisms. These data should be considered in the context
      of growing enthusiasm for resurfacing with new bearing surfaces and cementless
      fixation.

PMID- 17006373
TI  - Thromboembolic disease after total hip arthroplasty: who is at risk?
AB  - The strong activation of the clotting cascade that occurs during total hip
      arthroplasty places patients at increased risk for venous thromboembolism. The
      risk is higher in those patients with the following predisposing factors, listed
      in approximate order of importance: hip fracture; malignancy, particularly if
      associated with chemotherapy; antiphospholipid syndrome; immobility; history of
      venous thromboemholism; administration of tamoxifen; raloxifene; oral
      contraceptives or estrogen; morbid obesity; stroke; atherosclerosis; and an
      American Society of Anesthesiologists physical status classification of 3 or
      greater. The following risk factors are weak or controversial: advanced age;
      diabetes mellitus; congestive heart disease; atrial fibrillation; varicose veins;
      and smoking. However, 50% of patients who develop thromboembolism after total hip
      arthroplasty have no clinical predisposing factors. In a matched, controlled
      study, we defined the major genetic predispositions that increase the risk of
      venous thromboembolism after total hip arthroplasty: deficiency of antithrombin
      III (< 75%) and protein C (< 70%), and prothrombin gene mutation. Preoperative
      genetic screening in conjunction with the recognized clinical risk factors can
      help categorize postoperative venous thromboembolism risk and differentiate
      patients who can be protected with milder and safer prophylaxis (eg, aspirin,
      intermittent pneumatic compression) compared with those at higher risk who need
      to be anticoagulated.

PMID- 17006374
TI  - Is scapular endoprosthesis functionally superior to humeral suspension?
AB  - Humeral suspension was the most popular reconstructive procedure after total
      scapulectomy until the early 1990s. Since 1992 the senior author has been
      performing scapular endoprosthetic reconstruction after total scapulectomy
      whenever the rhomboids, latissimus dorsi, deltoid, and trapezius were preserved.
      We hypothesized that scapular endoprosthetic reconstruction resulted in better
      functional and cosmetic results than humeral suspension. From 1979 to 2003, 32
      consecutive patients had total scapulectomies. Reconstructions included humeral
      suspensions in 16 patients and scapular endoprostheses in 16 patients. Functional
      and cosmetic results were compared retrospectively between the two groups.
      Patients with scapular endoprostheses had better functional results and superior
      cosmesis as compared with patients with humeral suspension. The mean
      Musculoskeletal Tumor Society scores for patients with scapular endoprostheses
      and humeral suspensions were 78.5% and 58.5% respectively. Seven patients with
      scapular endoprostheses had greater than 40 degrees abduction and 11 patients
      with humeral suspensions could not abduct the shoulder greater than 20 degrees.
      Twelve patients with humeral suspensions and none with scapular endoprostheses
      wore shoulder pads or customized orthoses for cosmetic purposes. After total
      scapulectomy, scapular endoprosthetic reconstruction led to better functional and
      cosmetic results than humeral suspension and therefore we recommend performing
      this reconstructive procedure whenever the rhomboids, latissimus dorsi, deltoid,
      and trapezius are preserved.

PMID- 17006375
TI  - Postoperative infections of the thoracic and lumbar spine: a review of 18 cases.
AB  - We retrospectively reviewed 18 consecutive patients (age range, 19-81 years;
      average age, 55 years) with postoperative infections of the spine. Postdiscectomy
      laminectomy infections confined to the disc space (n = 2) were treated with
      percutaneous transpedicle drainage. Open debridement was performed in patients
      with an epidural or paraspinal abscess (n = 3). Infections after posterior
      instrumentation that manifested during the first postoperative month were treated
      with single (n = 3) or multiple debridements and delayed closure (n = 7), with
      preservation of instrumentation. Infections that presented more than 9 months
      after the initial operation (n = 3) were treated with open debridement and
      removal of instrumentation. The minimum followup was 1 year (mean 2 years, range,
      1-4 years). Infections in 17 of the 18 patients resolved effectively and one
      patient with metastatic cancer died of sepsis. Transpedicle drainage resulted in
      immediate relief of back pain. Instrumentation can be retained safely in patients
      with infections that manifest during the first month after implantation. Single
      surgical debridement is effective in selected cases. After repeated debridements,
      the presence of healthy granulation tissue in the wound and decreasing C-reactive
      protein activity were associated with safe and effective wound closure. Despite
      radiographic evidence of hardware loosening in infections manifested more than 9
      months after implantation, we removed hardware without destabilizing the spine.

PMID- 17006376
TI  - Effect of soy isoflavone protein and soy lecithin on endothelial function in
      healthy postmenopausal women.
AB  - OBJECTIVE: To assess the effects of soy isoflavone protein concentrate and soy
      lecithin on endothelial function, measured as flow-mediated dilation (FMD) of the
      brachial artery in healthy postmenopausal women. DESIGN: This was a randomized,
      double-blind, placebo-controlled crossover trial with 25 participants (mean age,
      61 years; body mass index, 25.46 kg/m2). The women underwent endothelial function
      testing at baseline and after 4 weeks of randomly assigned treatment with
      intervening 4-week washout periods. Treatment assignments included soy isoflavone
      protein (25 g/day) and soy lecithin (20 g/day), soy isoflavone protein (25 g/day)
      and placebo lecithin, placebo protein and soy lecithin (20 g/day), and double
      placebo. FMD and serum lipid levels were assessed at baseline and the end of each
      4-week treatment phase. RESULTS: Twenty-two women completed the trial. No
      statistically significant (P > 0.05) difference was seen in FMD between treatment
      groups. A trend was suggested with FMD highest after treatment with soy protein
      plus lecithin (7.50 +/- 9.85), followed by soy protein (5.51 +/- 10.11), soy
      lecithin (5.35 +/- 6.13), and lowest after placebo (4.53 +/- 7.84). Soy
      isoflavone protein and soy lecithin significantly increased the high-density
      lipoprotein/low-density lipoprotein ratio (soy isoflavone protein plus soy
      lecithin, 0.64 +/- 0.19, P < 0.0001; soy isoflavone protein plus placebo
      lecithin, 0.58 +/- 0.17, P = 0.0058; placebo protein plus soy lecithin, 0.65 +/-
      0.18, P < 0.0001) relative to the baseline value (0.49 +/- 0.15). CONCLUSIONS: In
      this sample of healthy postmenopausal women, soy isoflavone protein and soy
      lecithin significantly improved the lipid profile. A favorable influence on
      endothelial function could not be confirmed.

PMID- 17006377
TI  - Tibolone for the treatment of moderate to severe vasomotor symptoms and genital
      atrophy in postmenopausal women: a multicenter, randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: To demonstrate the safety and efficacy of tibolone (1.25 and 2.5 mg)
      in the treatment of moderate to severe vasomotor symptoms and symptoms associated
      with vaginal atrophy. DESIGN: A placebo-controlled, double-blind, randomized,
      multicenter study was conducted on 396 healthy postmenopausal women experiencing
      a minimum of 7 moderate to severe hot flashes per day (60 per week). Participants
      were randomized to receive tibolone 1.25 or 2.5 mg or placebo once daily for 12
      weeks. Assessments were done at weeks 4, 8, and 12. The severity and frequency of
      hot flashes were recorded in patient diaries on a daily basis. RESULTS: Tibolone
      2.5 mg significantly (P < 0.001) reduced the average number of hot flashes
      compared with placebo at week 4 (-7.82 vs -5.27), week 8 (-9.71 vs -5.86), and
      week 12 (-10.14 vs -5.85). The difference between tibolone 1.25 mg and placebo
      was significant (P < 0.001) at week 8 (-7.96) and week 12 (-8.32). Findings for
      the average daily severity of hot flashes were similar, with significantly
      greater reductions at week 4 (P < 0.05) and weeks 8 and 12 (P < 0.001) for
      tibolone 2.5 mg versus placebo and at weeks 8 and 12 for tibolone 1.25 mg versus
      placebo (P < 0.001). A menopausal atrophic symptom questionnaire revealed that
      tibolone 2.5 mg significantly (P < 0.05) reduced nocturia compared with placebo
      at weeks 4, 8, and 12 and urinary urgency at week 4. Compared with placebo, both
      doses of tibolone also significantly (P < 0.001) increased the vaginal maturation
      value from baseline. The overall incidence of adverse events was similar in all
      treatment groups. CONCLUSIONS: Tibolone is effective and well tolerated for the
      treatment of moderate to severe vasomotor symptoms and the effects of vaginal
      atrophy associated with menopause.

PMID- 17006378
TI  - Conversion of tibolone to 7alpha-methyl-ethinyl estradiol using gas
      chromatography-mass spectrometry and liquid chromatography-mass spectrometry:
      interpretation and clinical implications.
AB  - OBJECTIVE: Tibolone, a hormone therapy drug, is used to treat climacteric
      symptoms. This drug is rapidly metabolized into three major metabolites (3alpha
      hydroxytibolone, 3beta-hydroxytibolone, and Delta4-tibolone). One clinical study
      provided evidence of conversion of tibolone to another estrogenic metabolite,
      7alpha-methyl-ethinyl estradiol (MEE). However, no evidence of MEE formation was
      found in another study using the human aromatase enzyme. Because MEE was analyzed
      by gas chromatography-mass spectrometry (GC-MS), which requires derivatization,
      together with the fact that derivatization of some steroids may lead to
      aromatization, it is feasible that the MEE detected resulted from an artifact
      generated during the derivatization process. Hence, our objective was to assess
      whether tibolone is converted to MEE. DESIGN: We assayed MEE formation in a
      nonbiological system using GC-MS after derivatization and by analyzing MEE
      formation using liquid chromatography-mass spectrometry (LC-MS) in nonderivatized
      samples. RESULTS: MEE formation was evident in tibolone samples derivatized with
      either pentafluoropropionic anhydride or trimethylsilyl and analyzed by GC-MS.
      The amount of MEE formed increased with increasing amounts of tibolone (0.5, 1,
      2.5, and 5 microg) derivatized; however, relative to tibolone, the percentage of
      MEE formed remained constant and ranged between 0.22% and 0.29% of tibolone. In
      contrast to GC-MS, no MEE formation was seen when tibolone was analyzed by liquid
      chromatography-mass spectrometry without derivatization. CONCLUSIONS: Our
      findings prove that conversion of tibolone to MEE is an artifact that is
      generated in a GC-MS system and is largely due to the intense heating step
      involved in GC-MS. Caution should be exercised to extrapolate clinical
      implications from existing data on MEE formation using a GC-MS system.

PMID- 17006380
TI  - Is a prophylactic treatment by erythropoietin relevant to reduce red blood cell
      transfusion in the pediatric intensive care unit?
AB  - OBJECTIVE: An adult trial reported the efficacy of recombinant human
      erythropoietin in critically ill patients with a 19% decrease in red blood cell
      transfusion. Our aim was to evaluate the relevance of this prophylactic treatment
      in children hospitalized in a pediatric intensive care unit (PICU). DESIGN:
      Cohort study from January 1995 to December 2004. SETTING: University hospital
      PICU. PATIENTS: Children between 1 month and 18 yrs of age. INTERVENTIONS: We
      searched through a prospective databank for all children hospitalized in the PICU
      for > or =4 days (potential recipients of erythropoietin, as proposed in the
      adult trial) and transfused with red blood cells after day 7 following PICU entry
      (in whom erythropoietin might prevent anemia, according to results of the adult
      trial). MEASUREMENTS AND MAIN RESULTS: We found that 799 of 2,578 children (31%)
      were hospitalized for > or =4 days. The study group comprised 787 patients who
      were hospitalized for > or =4 days in the PICU and for whom full records were
      available. One hundred eighty-three children in this study group were transfused
      during their stay in the PICU (median age, 7 months; weight, 6.60 kg). Hemoglobin
      levels before transfusion (mean +/- sd) were 7.7 +/- 1.5 g/dL. These transfused
      children represented 23% of the study group and 7% of the total PICU admissions.
      Forty-seven children (6% of the study group, 2% of the total PICU admissions)
      were transfused with red blood cells after 7 days of hospitalization and could
      have benefited from a prophylactic treatment with erythropoietin. Relative risk
      to benefit of a prophylactic treatment by erythropoietin was higher in cases of
      mechanical ventilation (relative risk, 1.18) and inotropic treatment (relative
      risk, 1.72) and if the main diagnosis involved dermatological (relative risk,
      3.03) or oncologic disease (relative risk, 3.94). CONCLUSIONS: If we applied the
      results of the adult trial to our PICU, we would have to treat 31% of the
      children with prophylactic erythropoietin and thereby expect a reduction of one
      red blood cell transfusion for every 17 treated patients.

PMID- 17006379
TI  - Estrogen and raloxifene inhibit the monocytic chemoattractant protein-1-induced
      migration of human monocytic cells via nongenomic estrogen receptor alpha.
AB  - OBJECTIVE: To investigate the effects of estradiol (E2) and raloxifene on the
      migration of human monocytic THP-1 cells to endothelium. DESIGN: A prospective
      comparative study. THP-1 cells, a human acute monocytic leukemia cell line, were
      used for the study. Migration assays were performed using transwell inserts. THP
      1 cells were exposed to E2 or raloxifene in the presence of monocytic
      chemoattractant protein-1 (MCP-1), a major chemoattractant for monocytes. The
      cells were transfected with small interfering RNA (siRNA) against estrogen
      receptor (ER) alpha and ERbeta for gene silencing. ER expression was evaluated by
      Western blot analysis. RESULTS: MCP-1 induced the migration of the cells for 90
      minutes. The addition of E2 or raloxifene significantly inhibited the MCP-1
      induced migration for 90 minutes. Preincubation of THP-1 cells with an ER
      antagonist, ICI 182780, significantly attenuated the inhibitory effects of E2 and
      raloxifene. Whereas transfection with siRNA of ERalpha significantly attenuated
      the inhibition by E2 of MCP-1-induced monocyte migration, transfection with
      control siRNA or siRNA of ERbeta had no effect on the rapid inhibitory action of
      E2. Moreover, preincubation of THP-1 cells with a transcriptional inhibitor,
      actinomycin D, had no effect on the rapid inhibitory action of E2. CONCLUSIONS:
      Our findings suggest that both E2 and raloxifene inhibited the MCP-1-induced
      monocyte migration through nongenomic ERalpha. This result may explain one of the
      antiatherosclerotic effects of E2 and raloxifene on vasculature.

PMID- 17006381
TI  - Is there a "right" way to wean my patient from the ventilator? A critical
      appraisal of Randolph et al: Effect of mechanical ventilator weaning protocols on
      respiratory outcomes in infants and children: A randomized controlled trial (JAMA
      2002; 288:2561-2568).
AB  - OBJECTIVE: To review the findings and discuss the implications of mechanical
      ventilator weaning protocols in children. DESIGN: A critical appraisal of
      Randolph et al. Effect of mechanical ventilator weaning protocols on respiratory
      outcomes in infants and children: A randomized controlled trial. JAMA
      2002;288:2561-2568, and literature review. FINDINGS: There was no difference in
      ventilator weaning times between children randomized to a ventilator weaning
      protocol (pressure support, volume support, or no protocol). However, the study
      did show that increased sedative use during the first 24 hrs of weaning (the only
      time during which these data were collected) was an important predictor of
      weaning duration (p < .001) and weaning failure (p = .04). CONCLUSIONS: The
      majority of children are weaned from mechanical ventilation over a short period
      of time. Weaning protocols may not shorten this brief duration of weaning but may
      have other advantages such as improved collaboration between healthcare team
      members. Future research into the effects of sedation on weaning from mechanical
      ventilation is needed in children.

PMID- 17006382
TI  - Arterial pulse wave analysis: An accurate means of determining cardiac output in
      children.
AB  - OBJECTIVE: Cardiac output is a useful measure of myocardial performance. Standard
      methods of determining cardiac output are not without risk and can be problematic
      in children. Arterial pulse wave analysis (PulseCO), a novel, minimally invasive
      cardiac output determination technique, offers the advantage of continuous
      monitoring, convenience, and low risk. This technique has not been validated in
      children. The purpose of this study was to validate PulseCO as an accurate means
      of noninvasively determining real-time cardiac output in children. DESIGN:
      Prospective, single-center evaluation. SETTING: Children's hospital. PATIENTS:
      Any child with a structurally normal heart, undergoing hemodynamic evaluation in
      the cardiac catheterization laboratory, was included. INTERVENTIONS: A prograde
      right heart catheterization was performed, and cardiac output was determined
      using the thermodilution technique, via placement of a pulmonary arterial
      catheter. MEASUREMENTS AND MAIN RESULTS: Thermodilution results were compared
      with continuous real-time cardiac output measurements obtained with the PulseCO
      system, and they were then analyzed by standard correlation techniques and Bland
      Altman analysis. Twenty patients were evaluated with a median age of 10.5 yrs and
      a median weight of 25 kg. The mean thermodilution cardiac index was 3.3 +/- 0.9
      L/min/m, whereas the mean PulseCO cardiac index was 3.1 +/- 0.9 L/min/m. Standard
      Pearson correlation tests revealed a correlation coefficient of .94 (p < .001).
      Bland-Altman analysis revealed excellent clinical agreement with a mean
      difference of 0.19 L/min/m and a precision of 0.28 L/min/m at 2 sd. CONCLUSIONS:
      Arterial pulse wave analysis by the PulseCO system provides a novel, minimally
      invasive method of determining real-time cardiac output in children.

PMID- 17006383
TI  - Successful use of surfactant to treat severe intrapulmonary hemorrhage after
      iatrogenic lung injury--A case report.
AB  - OBJECTIVE: To describe the beneficial clinical effect of the use of surfactant in
      a patient with severe unilateral pulmonary hemorrhage after iatrogenic lung
      injury during corrective surgery for congenital heart defects. DESIGN: Case
      report. SETTING: Pediatric cardiac intensive care unit of a tertiary care
      hospital. PATIENT: An 11-wk-old boy. INTERVENTIONS: Intratracheal instillation of
      4 mL (100 mg) of surfactant (Survanta) per kilogram of body weight to treat
      profound and refractory hypoxia and hypercapnia despite high-ventilation
      pressures, high respiratory rate, and the use of nitric oxide caused by severe
      pulmonary hemorrhage and atelectasis. MEASUREMENTS AND MAIN RESULTS: The
      aggressive ventilation variables could be reduced within the following 2 hrs
      after surfactant use (from Fio2 0.8, peak inspiratory pressure 36 cm, positive
      end-expiratory pressure 10 cm, respiratory rate 50, tidal volume 63 mL, and
      nitric oxide 10 ppm to Fio2 0.4, peak inspiratory pressure 28 cm, positive end
      expiratory pressure 10, respiratory rate 40, tidal volume 38 mL, and nitric oxide
      5 ppm). There was rapid improvement of clinical variables (inotropic support,
      chest radiograph) as well as oxygenation (Pao2 from 56 to 149 mm Hg), CO2
      exchange (Paco2 from 85 to 39 mm Hg), and acidosis (from pH 7.13 to 7.44).
      CONCLUSIONS: The administration of surfactant may be a promising approach to
      treat severe respiratory failure caused by severe pulmonary hemorrhage.

PMID- 17006384
TI  - Ventricular peritoneal shunt infection resulting from group B streptococcus.
AB  - OBJECTIVE: To report, to our knowledge, the first case of a ventricular
      peritoneal shunt infection by group B streptococcus occurring in infancy. DESIGN:
      Descriptive case report. SETTING: Neonatal intensive care unit in a tertiary
      referral military hospital. PATIENT: A 3-month-old, former preterm infant with a
      case of postoperative ventricular peritoneal shunt infection by group B
      streptococcus occurring in infancy. INTERVENTIONS: The infant's shunt infection
      was treated with a prolonged course of antibiotics, shunt removal, and eventual
      shunt replacement. He developed a persistently enlarging third ventricular region
      cyst, which ultimately required endoscopic surgical fenestration. MEASUREMENTS
      AND MAIN RESULTS: Currently, at 25 months of age, the patient has some moderate
      developmental delays but is otherwise healthy and making progress with no
      evidence of any recurrent infection CONCLUSIONS: Group B streptococcus should be
      considered as a potential pathogen in ventricular peritoneal shunt infections in
      infants even outside of the immediate neonatal period. Providers caring for
      infants should be especially cognizant of the potential risk for nosocomial
      infections in former premature neonates, especially following high-risk surgical
      procedures. Prompt recognition of ventricular peritoneal shunt infections and
      management to include early shunt removal and appropriate antibiotic coverage are
      recommended in an effort to optimize outcome.

PMID- 17006385
TI  - Use of fenoldopam to increase urine output in a patient with renal insufficiency
      secondary to septic shock: A case report.
AB  - OBJECTIVE: We describe the use of fenoldopam to increase urine output in a
      pediatric patient with sepsis, heart failure, oliguria, and volume overload.
      DESIGN: Case report. SETTING: A tertiary pediatric intensive care unit. PATIENT:
      A 17-year-old male who was being treated for acute lymphoblastic leukemia and was
      admitted from outside the hospital to the pediatric intensive care unit, in
      septic shock, after a course of chemotherapy. INTERVENTIONS: A continuous
      fenoldopam infusion of 0.03 microg/kg/min was added to a regimen of multiple
      inotropic and vasopressor agents and a furosemide continuous infusion.
      MEASUREMENTS AND MAIN RESULTS: Urine output increased 586% 12 hrs after starting
      the fenoldopam infusion and 775% from baseline 24 hrs after starting the
      infusion. Diuretics were decreased while maintaining adequate urine output. No
      hypotension was noted. CONCLUSIONS: Fenoldopam increased urine output in a
      pediatric patient who was in septic shock and oliguria. The mechanism for this
      effect is unclear, and further trials are necessary to determine the role of
      fenoldopam in this patient population.

PMID- 17006386
TI  - Acute thiamine deficiency in diabetic ketoacidosis: Diagnosis and management.
AB  - OBJECTIVE: Persistent encephalopathy in a patient with diabetic ketoacidosis is
      often feared as a sign of cerebral edema. Although thiamine deficiency is a rare
      diagnosis in children, marginal nutritional status and osmotic diuresis may be
      risk factors. The objective was to describe a heretofore unreported cause of
      encephalopathy in a child with diabetic ketoacidosis and review the mechanisms
      and pathophysiology of thiamine deficiency in this clinical scenario. DESIGN:
      Case report and review of the literature. SETTING: Pediatric intensive care unit
      of a tertiary care pediatric hospital. PATIENT: A 13-yr-old girl. INTERVENTIONS:
      Treatment of dehydration and hyperglycemia, osmotherapy, and intravenous thiamine
      administration. MEASUREMENTS AND MAIN RESULTS: The patient presented with new
      onset diabetes mellitus, severe diabetic ketoacidosis, and significant
      encephalopathy. Despite biochemical improvement with treatment of dehydration and
      hyperglycemia, her encephalopathy persisted. Computed tomography did not show
      cerebral edema and she showed no response to osmotherapy. Quantitative and
      functional assays revealed severe thiamine deficiency. The patient showed an
      immediate and dramatic response to intravenous thiamine administration.
      CONCLUSIONS: The clinical improvement as well as lab investigations suggests that
      thiamine deficiency was the cause of this child's encephalopathy. Because
      potential mechanisms exist for thiamine deficiency in diabetes mellitus and
      institution of insulin and glucose therapy may stress thiamine body stores,
      thiamine deficiency should be considered in children with diabetic ketoacidosis
      whose encephalopathy does not improve with improvement of biochemical status.

PMID- 17006387
TI  - Urinary S100B concentrations are increased after brain injury in children: A
      preliminary study.
AB  - OBJECTIVE: S100B is a renally excreted protein concentrated in glial cells of the
      nervous system. Increases in serum S100B concentrations reflect brain injury.
      However, increases in serum are rapid and transient and therefore may be of
      limited use in certain patients. Urinary S100B concentrations may be able to
      provide information about brain injury in this subgroup of patients. DESIGN:
      Prospective, descriptive study. SETTING: Level I trauma center. PATIENTS: Fifteen
      children with acute traumatic or hypoxemic brain injury (subjects) and 14 healthy
      controls. INTERVENTIONS: Urine and serum samples were collected from subjects and
      controls. Serial samples were collected in brain injury subjects up to every 12
      hrs for 3 days. S100B concentrations were measured by enzyme-linked immunosorbent
      assay (Nanogen, San Diego CA). Outcome was assessed by Glasgow Outcome Scale
      score. MEASUREMENTS AND MAIN RESULTS: Urinary S100B concentrations were
      detectable in 80% of subjects with increased serum S100B concentrations and 0% of
      controls. Peak urinary S100B concentrations occurred significantly later than
      peak serum S100B concentrations: 55.3 (29.8) (mean [sd]) vs. 14.6 (11.8) hrs
      after injury (p = .002). All subjects with an undetectable urinary S100B had a
      good outcome vs. only 20% of subjects with a detectable urinary S100B. Subjects
      with increased serum S100B were more likely to have a poor outcome than those
      with normal S100B (p = .01). CONCLUSIONS: Increases in urinary S100B are found in
      the majority of children with acute brain injury and an increased serum S100B.
      Urinary S100B concentrations peak later than serum concentrations, suggesting
      that measurement of urinary S100B may be helpful in subjects in whom early serum
      S100B is unavailable. Urinary and/or serum S100B concentrations may be useful to
      assist in the prediction of outcome after pediatric brain injury.

PMID- 17006388
TI  - Blunt bowel and mesenteric injuries in children: Do nonspecific computed
      tomography findings reliably identify these injuries?
AB  - OBJECTIVE: Abdominal computed tomography has proven accurate for the detection of
      pediatric solid organ injuries following blunt abdominal trauma but is less
      reliable in detecting blunt bowel and mesenteric injuries (BBMI). The purpose of
      this study was to determine the significance of nonspecific findings on abdominal
      computed tomography (CT) scan in children at risk for BBMI. DESIGN: Retrospective
      chart review. SETTING: Regional pediatric trauma center. PATIENTS: All patients
      who received an abdominal CT scan as part of their evaluation following blunt
      abdominal trauma over a 10-yr period (September 1991 to September 2001).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Individual records were
      reviewed by one of the authors and analyzed for age, gender, mechanism of injury,
      diagnostic studies and procedures, results of initial CT scan, treatment,
      surgical procedures, complications, and outcome. Patients were excluded if they
      suffered penetrating trauma, had an abdominal CT scan performed at another
      institution, had a surgical procedure before CT scan, or had incomplete records.
      A total of 2,114 patients met inclusion criteria. Sixty-five percent were male
      and ages ranged from 3 wks to 18 yrs. There were 178 patients who had at least
      one nonspecific finding on abdominal CT scan suggestive of BBMI; 151 patients had
      one finding, 24 patients had two findings, and three had three findings. The risk
      of BBMI increased with the number of nonspecific findings (positive predictive
      value = 11% with at least one finding and 44% with two or more findings). This
      increase in positive predictive value, however, was accompanied by a reduction in
      sensitivity (62% and 37%, respectively). A total of 32 patients had surgically
      proven BBMI. Of these, eight had a single nonspecific finding on CT scan, ten had
      two findings, and two had three findings (12 patients had no CT findings
      suggestive of BBMI). There were complications in four of the 32 patients with
      BBMI and one death (due to laceration of the superior mesenteric artery). The
      complications appeared to occur independent of the time to surgical intervention.
      CONCLUSIONS: The presence of multiple nonspecific findings on abdominal CT scan
      does not reliably predict BBMI in children. Children also appear to suffer
      complications from BBMI less frequently than adults, regardless of the time to
      surgery. Therefore, nonspecific findings alone do not warrant surgical
      exploration. The decision to operate should instead be based on clinical data
      that include serial physical examinations.

PMID- 17006389
TI  - Healthcare-associated infection in pediatric patients on extracorporeal life
      support: The role of multidisciplinary surveillance.
AB  - OBJECTIVE: To describe the use of a multidisciplinary approach to sepsis
      surveillance and evaluate impact on outcome. DESIGN: Prospective clinical study
      or clinical audit cycle. SETTING: Tertiary pediatric extracorporeal membrane
      oxygenation (ECMO) center. PATIENTS: Patients were 215 children supported with
      ECMO January 1999 to December 2004. INTERVENTIONS: A multidisciplinary team met
      monthly to evaluate cases of bloodstream infection and mediastinitis, review
      trends, and update unit policies. Changes in practice were made at the end of
      2001 in order to address a perceived high rate of sepsis: a) reeducation; b)
      introduction of electively preprimed ECMO circuits; and c) preference for neck
      rather than chest cannulation in cardiac patients. Prophylactic antibiotics were
      used from preprocedure for 24 hrs only throughout the study. MEASUREMENTS AND
      MAIN RESULTS: Over the entire study period, 39 children had 47 septic episodes,
      with a rate of 24.9 per 1000 ECMO days. Multiple logistic regression analyses
      indicated that infection was associated with duration of ECMO support (odds ratio
      1.24; 95% confidence interval 1.15, 1.35 per day) and case type: Closed vs. open
      chest was protective in cardiac patients (odds ratio 0.08; 95% confidence
      interval 0.01, 0.50). Infection increased the odds of death by 2.01 (95%
      confidence interval 1.00, 4.05), but this effect was less important than case
      type and ECMO days. After policy changes were implemented, there was a reduction
      in sepsis from 29.3 to 20.1 episodes per 1000 ECMO days. There was reduced sepsis
      in respiratory patients: neonates from 28.0 to 6.6 and pediatric patients from
      42.4 to 16.9 episodes per 1000 ECMO days. Despite policy changes, sepsis remained
      a problem in cardiac patients with open sternum: 65.1 per 1000 ECMO days.
      CONCLUSIONS: ECMO support is a high-risk setup for nosocomial infection, in
      particular for cardiac patients with open sternum for whom antibiotic prophylaxis
      is justified. Multidisciplinary surveillance offers an excellent approach for
      quality improvement in this challenging field.

PMID- 17006390
TI  - Childhood obesity increases duration of therapy during severe asthma
      exacerbations.
AB  - OBJECTIVES: Childhood obesity contributes to a wide array of medical conditions,
      including asthma. There is also increasing evidence in adult patients admitted to
      the intensive care unit (ICU) that obesity contributes to increased morbidity and
      to a prolonged length of stay. We hypothesized that obesity is associated with
      the need for increased duration of therapy in children admitted to the ICU with
      status asthmaticus. DESIGN: Retrospective cohort study. SETTING: A tertiary
      pediatric ICU in a university-affiliated children's hospital. PATIENTS: We
      retrospectively examined data from all children older than 2 yrs admitted to the
      ICU with status asthmaticus between April 1997 and June 2004. Children were
      classified as normal weight (<95% weight-for-age percentile) or obese (>95%
      weight-for-age). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 209
      children admitted to the ICU with asthma, 45 (22%) were obese. Compared with
      children of normal weight, the obese children were older (9.7 +/- 4.4 vs. 8.0 +/-
      4.3 yrs, p = .02), more likely to be female (60% vs. 37%, p < .01), and more
      likely to have been admitted to the ICU previously (40% vs. 20%, p = .01). The
      obese children also had a statistically significant difference in race (more
      likely to be Hispanic) and in baseline asthma classification (more likely to have
      persistent asthma). Despite similar severity of illness at ICU admission, obese
      children had a significantly longer ICU length of stay (116 +/- 125 hrs vs. 69 +/
      57 hrs, p = .02) and hospital length of stay (9.8 +/- 7.0 vs. 6.5 +/- 3.4 days,
      p < .01). Obese children also received longer courses of supplemental oxygen,
      continuous albuterol, and intravenous steroids. CONCLUSIONS: Childhood obesity
      significantly affects the health of children with asthma. Obese children with
      status asthmaticus recovered more slowly from an acute exacerbation, even after
      adjustment for baseline asthma severity and admission severity of illness.

PMID- 17006391
TI  - Abnormal vascular tone in infants and children with lung hypoplasia: Findings
      from cardiac catheterization and the response to chronic therapy.
AB  - OBJECTIVE: We describe four cases of chronic pulmonary hypertension in infants
      and children with chronic lung disease and pulmonary hypoplasia due to severe
      congenital diaphragmatic hernia (CDH) or congenital cystic adenomatoid
      malformation (CCAM). We report data from cardiac catheterization under various
      conditions: baseline respiratory support and room air, hyperoxic and inhaled
      nitric oxide challenge. We further report cardiac catheterization measures after
      chronic pulmonary vasodilator therapy with sildenafil alone or a combination of
      sildenafil and inhaled nitric oxide (three patients). DESIGN: Case series.
      SETTING: Tertiary academic center. PATIENTS: Infants and children ages 0-11 yrs
      with CDH (n = 3) or CCAM (n = 1) with evidence of chronic pulmonary hypertension
      by echocardiogram and cor pulmonale (n = 3). INTERVENTIONS: Catheterization and
      pulmonary vasodilator therapy. MEASUREMENTS AND MAIN RESULTS: Pulmonary vascular
      resistance, pulmonary arterial pressure, and changes in these measures were
      assessed. A 20% change in pulmonary vascular resistance was considered a
      clinically significant response. Ten catheterizations were performed in four
      patients. All patients had elevated pulmonary vascular resistance and pulmonary
      arterial pressures at initial catheterizations and significant vasodilation
      during inhaled nitric oxide. CONCLUSIONS: Chronic lung disease following
      pulmonary hypoplasia from CDH and CCAM is associated with abnormal pulmonary
      vascular tone in infants and children with evidence of chronic pulmonary
      hypertension. Chronic pulmonary vasodilator therapy may improve pulmonary
      vascular function and enhance lung growth in infants and children who are treated
      during their period of potential for rapid lung growth.

PMID- 17006392
TI  - Characteristics and outcomes of interhospital transfers from level II to level I
      pediatric intensive care units.
AB  - OBJECTIVE: To examine the characteristics, resource utilization, and outcomes for
      transfer admissions from level II to level I pediatric intensive care units
      (PICUs). DESIGN: Retrospective study. SETTING: A 16-bed level I PICU in a
      tertiary care children's hospital. PATIENTS: All transfer admissions from level
      II PICUs from January 1, 1997, through December 31, 2003; admissions for cardiac
      surgery were excluded. Patient characteristics, resource utilization, and
      outcomes were described and then compared across predefined strata (low <5%,
      moderate 5-30%, and high >30%) of predicted probability of death. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Of 168 transfer admissions, 45%, 30%, and
      25% were in the low, moderate, and high mortality risk groups, respectively.
      Length of stay at the referring PICU was shortest for the high-risk admissions.
      The most frequent diagnoses among all risk groups were respiratory failure (49%)
      and sepsis (14%). High-risk admissions were more likely to receive advanced
      therapies such as extracorporeal membrane oxygenation (41.5% high risk vs. 39.2%
      moderate vs. 6.6% low risk, p < .01) and renal replacement therapy (34.2% vs.
      17.7% vs. 2.6%, p < .01). The high-risk admissions had longer PICU length of stay
      and the highest death rates (34% vs. 10% vs. 4%, p < .01) when compared with the
      moderate- and low-risk admissions, respectively. CONCLUSIONS: This study
      highlights significant differences in patient characteristics, resource
      utilization, and outcomes across mortality risk-stratified groups of critically
      ill and injured children transferred from level II to level I PICU care. Further
      studies are warranted to investigate decision making that prompt inter-PICU
      transfers.

PMID- 17006393
TI  - Correlation of near-infrared spectroscopy with perfusion parameters at the
      hepatic and systemic levels in an endotoxemic shock model.
AB  - BACKGROUND: To determine the correlation of near-infrared spectrophotometry
      (NIRS) readings from the liver surface with invasive measurements of blood flow
      and tissue perfusion parameters in an animal model of endotoxemic shock.
      MATERIAL/METHODS: Laparotomy was performed in 12 Yorkshire piglets, and
      ultrasound blood flow probes were placed on the hepatic artery and portal vein.
      Hepatic vein, portal vein, and femoral artery catheters were inserted for
      intermittent blood sampling, and a pulmonary artery catheter was inserted via the
      jugular vein for cardiac output measurements. Near-infrared spectrophotometry
      optodes were placed across the right hepatic lobe. Endotoxemic shock was induced
      by continuous infusion of Escherichia coli lipopolysaccharide 055: B5. Pearson
      correlations were calculated between the perfusion parameters and the near
      infrared spectrophotometry (NIRS) readings. RESULTS: After endotoxemic shock
      induction, liver blood flow decreased from 144 +/- 36 to 62 +/- 24 ml*min(-1)*100
      g(-1) and oxygen delivery to the liver decreased from 20 +/- 6 to 7 +/- 4 ml*min(
      1)*100 g(-1). Near-infrared spectrophotometry readings of oxyhemoglobin
      concentration decreased by 11.7+/-15.1 micromol*L(-1), and readings of
      deoxyhemoglobin concentration increased by 12.3 +/- micromol*L(-1). There were
      significant correlations (p < 0.05 for r2 > 0.11) between the oxyhemoglobin
      readings and liver oxygen delivery (r2 = 0.58), liver blood flow (r2 = 0.73) and
      cardiac output (r2 = 0.80). Deoxyhemoglobin readings highly correlated (p < 0.05
      for r2 > 0.11) with mixed venous lactate (r2 = 0.87) and with hepatic vein
      lactate (r2 = 0.82). CONCLUSIONS: Noninvasive near-infrared spectrophotometry
      measurements of hepatic oxyhemoglobin and deoxyhemoglobin correlate with liver
      hemodynamics as well as with global and specific organ perfusion parameters and
      may serve, in the future, as a useful tool to monitor tissue perfusion in septic
      patients.

PMID- 17006394
TI  - Role of sphingosine kinase activity in protection of heart against ischemia
      reperfusion injury.
AB  - BACKGROUND: Sphingosine kinase (SKase) has been implicated in the protection of
      hearts from ischemia/reperfusion injury. This hypothesis was further examined.
      MATERIAL/METHODS: Changes in SKase activity and cardiac function (left
      ventricular developed pressure, LVDP, and infarct size) in response to ischemia
      and reperfusion were studied in adult rat hearts by the ex vivo Langendorff
      method. Following initial equilibration or preconditioning, there was 45 min no
      flow ischemia and then 45 min of reperfusion. RESULTS: SKase activity declined
      61% during ischemia and did not recover upon reperfusion. LVDP also did not
      recover upon reperfusion and the infarct size was 47%. A short 30 min period of
      ischemia was associated with variable recovery of SKase activity that directly
      correlated with LVDP recovery. Preconditioning of hearts reduced the decrease in
      SKase activity during ischemia by half, and upon reperfusion activity returned to
      normal. The LVDP recovered 79% and infarct size was small. Preconditioned hearts
      had higher S-1-P levels after ischemia/reperfusion relative to non-preconditioned
      hearts. The decline in SKase activity during ischemia of preconditioned hearts
      could not be mimicked in vitro by treatment with protein phosphatases. Attempts
      to alter activity of SKase from control, preconditioned, ischemic, or reperfused
      hearts by phosphorylation with ERK1/2 were unsuccessful. Treatment of non
      preconditioned hearts at reperfusion with 100 nM S-1-P improved recovery of LVDP.
      The SKase inhibitor dimethylsphingosine blocked hemodynamic recovery in
      preconditioned hearts. CONCLUSIONS: The data support a role for SKase activity in
      recovery of hemodynamic function after ischemic injury and also in the
      cardioprotective effect of preconditioning.

PMID- 17006395
TI  - Short term lead exposure induces a stress-like response in adult mice.
AB  - BACKGROUND: Developmental and perinatal lead exposure in rats affects the
      Hypothalamus-Pituitary-Adrenal Cortex (HPA) axis function resulting in elevated
      corticosterone blood levels thus affecting the level of stress responsivity of
      the offspring. The majority of the studies on lead exposure and stress have been
      done by exposing the animal indirectly during gestation, or lactation periods.
      This study presents evidence supporting that short term lead exposure affects a
      stress-like response in adult lead-exposed mice. MATERIAL/METHODS: DBA/2J mice
      were exposed to three different lead concentrations, 250, 500 and 1000 ppm, in
      the drinking water for a two week period. After the exposure period the animals
      were subjected to behavioral tests, i.e., social contact, and the plus maze using
      a computer-assisted videomonitoring system, Videomex-V (Columbia Instruments).
      The levels of ACTH and corticosterone in plasma were also measured using a
      Radioimmunoassay (RIA). RESULTS: Exposed animals displayed a significant decrease
      in the length of time the mice pairs spent within social contact distance (5.18
      +/- 0.58 seconds for controls and 3.23 +/- 0.34 seconds for 1000 ppm exposure),
      and a significant decrease in the percent of time the mice stayed in the open
      arms of the plus maze (7% for controls and 1% for 1000 ppm exposure) a measure
      indicator of anxiety. In addition exposed mice showed increased blood levels of
      ACTH (573 +/- 106 microg/dL for 1000 ppm and 127 +/- 25 microg/dL for control
      mice) and corticosterone (195.12 +/- 52.47 controls and 87.33 +/- 10.94 for
      exposed). CONCLUSIONS: These results support the hypothesis that exposure to lead
      of the adult mice affects a behavioral and hormonal response consistent with
      stress.

PMID- 17006396
TI  - Innate anti-viral immunity is associated with the protection elicited by the
      simian immunodeficiency virus (SIV) live attenuated virus vaccine in cynomolgus
      monkeys.
AB  - BACKGROUND: The Delta-nef live attenuated virus vaccine approach offered in the
      SIV-macaque model the opportunity to identify humoral and cell-mediated immune
      responses associated with protection against viral infections. In addition,
      soluble factors different from those related to specific immune responses appear
      to correlate with the establishment and maintenance of the protective status.
      MATERIAL/METHODS: Investigated were: 1) the ability of CD8+ T cells from
      cynomolgus monkeys vaccinated with SIV Delta-nef and long-term protected against
      sequential SIVs and SHIV challenges to inhibit in vitro SHIV replication in an
      acute infection cell system, 2) the ability of cell-free supernatants from CD8+ T
      cell cultures to inhibit replication of HIV in chronically infected cells, and 3)
      whether the antiviral activity of CD8+ T cells correlated with IFNgamma
      production. RESULTS: Soluble factor(s) secreted by CD8+ T cells from Delta-nef
      vaccinated monkeys significantly inhibited SHIV replication in an autologous cell
      system. This effect was not dependent on beta-chemokine secretion and correlated
      with an increased IFNgamma production. In addition, since supernatants from CD8+
      T cells inhibited HIV production in chronically infected monocytic cells, the
      suppressive activity was not related to the viral strain. CONCLUSIONS:
      Vaccination with the live attenuated virus induces both a CD8+ T cell-dependent
      antiviral activity and IFNgamma responses potentially responsible for the
      protection from challenge with heterologous highly pathogenic SHIV89.6P. It is
      conceivable that boosting the "natural" along with the antigen-specific immunity
      is a desirable outcome to improve the protective efficacy of any vaccine
      approach.

PMID- 17006397
TI  - The effect of a Health Realization/Innate Health psychoeducational seminar on
      stress and anxiety in HIV-positive patients.
AB  - BACKGROUND: Chronic stress and depression have a negative impact on immune
      functioning and threaten the well-being of HIV-positive patients. Although
      therapy methods, such as Cognitive Behavioral Therapy, have been shown to reduce
      stress and depression in such patients, not all patients are willing or able to
      undergo therapy over time. The Health Realization/Innate Health (HR/IH)
      psychoeducational approach is a brief intervention alternative that can be
      presented in a classroom setting. It engages participants' innate capacity to
      realize peace of mind. MATERIAL/METHODS: Eight volunteer participants from
      patients in the Positive Health Clinic at West Virginia University School of
      Medicine attended a 1-1/2 day HR/IH seminar called "Finding Your Natural Peace of
      Mind". Shortly before the seminar started, the Brief Symptom Inventory (BSI) was
      administered by a Clinic staff member. The BSI was administered again immediately
      following the seminar. The BSI was mailed to the participants four weeks
      following the seminar with a return envelope. Participants' confidentiality was
      maintained through a coded ID. Pre-, post- and follow-up results were compared.
      RESULTS: Each case was evaluated individually. The participant who pre-tested in
      the "psychiatric inpatient" range of the BSI showed no change after the seminar
      or at follow-up. The participants who tested in the non-patient normal range
      before the seminar showed some improvement after and at follow-up. The
      participants who scored in the "psychiatric outpatient" range entering the
      seminar all showed improvement that was sustained upon follow-up. CONCLUSIONS:
      The HR/IH psychoeducational approach deserves further study as a brief
      intervention for stress-reduction in HIV-positive patients.

PMID- 17006398
TI  - The effect of aging on conductive heat exchange in the skin at two environmental
      temperatures.
AB  - BACKGROUND: Ageing diminishes the blood flow (BF) response of the skin to
      autonomic stressors. While the diminished response of skin BF to global heating
      has been well documented, the effect of this reduction in skin BF on the ability
      of the skin to dissipate heat has not. When heat is added to the skin by the
      application of hot packs, if heat is not adequately removed, the skin can become
      dangerously hot and become damaged. The present investigation examined the heat
      dissipating properties of the skin in older individuals. This study has
      importance for the therapeutic application of hot packs which might cause burns
      easier in older people. MATERIAL/METHODS: In the present investigation, 10
      younger and 10 older subjects were examined. The average age of the younger group
      was 25.9+/-3.4 years and the older group was 60 +/- 5.8 years. Heat was applied
      through a 49 gram brass probe that was heated to 41 degrees C and by a Peltier
      junction in a cool and warm environment. RESULTS: Skin required about 20 calories
      of heat to raise skin temperature 1 degrees C the cool room and double this
      Figure in the warm room. Ageing reduced the caloric requirement to increase skin
      temperature under both conditions (p < 0.01). CONCLUSIONS: The results of the
      experiments showed that older individuals had impaired ability of the skin to
      dissipate heat in both environments. Special precautions should be taken in
      physical therapy when applying hot packs in older populations.

PMID- 17006399
TI  - Dukes' classification as a prognostic factor in patients with squamous cell
      carcinoma of the thoracic esophagus undergoing combined-modality treatment.
AB  - BACKGROUND: Several disadvantages of the TNM classification have resulted in a
      search for a simpler, clearer, and more reliable staging system for esophageal
      cancer. We evaluated Dukes' classification as a prognostic indicator in 81
      patients with squamous cell carcinoma of the thoracic esophagus treated with
      combined-modality therapy. MATERIAL/METHODS: The pathological staging was
      determined according to the TNM and Dukes' classification. The cumulative
      survival rates were calculated using the Kaplan-Meier method. The differences in
      survival between the patients in particular stages of both classifications were
      estimated with the log-rank test. RESULTS: The differences in cumulative survival
      rates between TNM I and TNM IIa, between TNM IIa and TNM IIb and between TNM IIb
      and TNM III patients were 20.2% (37.2 vs. 46.6), 27.5% (46.6 vs. 33.8) and 60.7%
      (33.8 vs. 13.3), respectively, and were not statistically significant (P = 0.58,
      P = 0.53 and P = 0.18). The cumulative survival rates for TNM III and TNM IV
      patients were similar (13.3 and 14.3). The difference in cumulative survival
      rates between Dukes' A and B patients amounted to 52.5% (54.3 vs. 25.8), which
      was statistically significant (P = 0.02). The difference in cumulative survival
      rates between Dukes' B and C patients was 41.5% (25.8 vs. 15.1), but fell short
      of statistical significance (P = 0.12). The cumulative survival rates for Dukes'
      C and D patients were similar (15.1 and 16.6). CONCLUSIONS: Dukes' staging system
      for esophageal cancer is simpler, clearer and more accurate, and could thus be a
      better prognostic tool than the TNM classification.

PMID- 17006400
TI  - Influence of 12-week exercise training on fat mass percentage in adolescents with
      Down syndrome.
AB  - BACKGROUND: Current findings suggest that more attention needs to be given to the
      increase in body mass achieved by disabled populations, especially by individuals
      with mental retardation, to minimize long-term negative health consequences.
      Accordingly, it would be of interest to design adequate strategies based on
      physical activities that may be easily performed to ensure adherence as a healthy
      lifestyle choice for these populations. MATERIAL/METHODS: To attain this goal, 22
      male adolescents with Down's syndrome (mean age: 16.2 +/- 1.0 years) underwent a
      12-week physical exercise intervention consisting of three sessions of one hour
      per week in both water and on land for 12 weeks. Fat mass percentage was
      calculated from anthropometric measurements according to the Durnin-Womersley
      equation. A paired t test was performed to evaluate possible differences in
      antropometrical characteristics between before and after the physical exercise
      intervention. RESULTS: According to the body mass index, it was observed that
      31.8% of the studied individuals presented overweight and 27.3% of them were
      obese before starting our experiment. The mean value of the percentage of fat
      mass was reduced significantly, from 31.8 +/- 3.7% to 26 +/- 2.3%, at the end of
      the study (p = 0.021). CONCLUSIONS: We may conclude that the adolescents with
      Down's syndrome were able to reduce their fat mass percentage significantly when
      performing a 12-week training program, which could have important impact on the
      comorbidity associated with obesity and on the quality of life of this
      population.

PMID- 17006401
TI  - Low-dose oral contraceptive to re-induce menstrual bleeding in amenorrheic women
      on DMPA treatment: a randomized clinical trial.
AB  - BACKGROUND: Depot medroxy progesterone acetate (DMPA) is one of the most reliable
      contraceptive methods with a failure rate less than 0.3 percent. It is injected
      every three months and Although it has many advantages over many other hormonal
      contraceptives, But a major disadvantage of it is bleeding disorders which
      comprise most of the discontinuance reasons. Our Aim was to study bleeding
      complications of DMPA when used as a contraceptive in Ardabil district and
      clinical trial of LD and Ethynil oestradiol in controlling these complications.
      MATERIAL/METHODS: All the 917 women who referred to ardabil's health centers for
      having a DMPA injection for the first time, were entered into a longitudinal
      study. Those complaining of menstrual cessation were entered into a double
      blinded randomized clinical trial. Data were collected by means of 9
      questionnaires 7 of them used for descriptive and 2 for clinical trial study.
      Data was analyzed by SPSS statistical package. RESULTS: Those DMPA users with a
      cesarean section history had a higher chance of bleeding complications. Four
      hundred forty-four of the 917 women receiving the injection discontinued using it
      before the end of the study period. The main reason for discontinuation (in 70%)
      was irregular menstrual bleedings and menstrual cessation. In the clinical trial
      of women with bleeding cessation, 70% of those receiving the LD-OC pill
      experienced menstrual bleedings again, compared with only 22.7% in the placebo
      group. The discontinuation rate in the drug group was lower than in the placebo
      group as well (p < 0.05). CONCLUSIONS: Treating menstrual cessation caused by
      DMPA with LDs, improves the complication and decreases the discontinuance rate.

PMID- 17006402
TI  - Application of fluorescent in situ hybridization (FISH) for the detection of
      Helicobacter pylori.
AB  - BACKGROUND: Peptic ulceration following infection of the stomach with H. Pylori
      is a common disease. Accurate and rapid detection of the bacteria can lead to the
      implementation of appropriate treatment and recovery. Chronic infection of the
      gastric milieu with H. Pylori may lead to gastric carcinoma. Routine detection of
      this bacterium in peptic ulcer is based on the urease test and culture of peptic
      biopsies. Unfortunately, the sensitivity and specificity of both tests are not
      satisfying. Molecular techniques have been successfully applied for the rapid and
      accurate detection of bacterial agents in clinical samples. This study was
      undertaken to evaluate the sensitivity and specificity of fluorescent in situ
      hybridization (FISH) in the detection of H. Pylori in patients suffering from
      dyspepsia. MATERIAL/METHODS: One hundred gastric biopsy samples taken by
      endoscopy from the antrum and corpus of the stomach were tested by FISH and
      compared with the conventional culture method complemented by biochemical tests.
      RESULTS: FISH detected H. Pylori in 48 clinical samples, while the conventional
      method detected 42 samples. The sensitivity and specificity of FISH for the
      detection of H. Pylori were calculated as 98% and 100%, respectively.
      CONCLUSIONS: The findings of this study suggest that FISH is a highly suitable
      and rapid method for diagnosing H. Pylori. Especially when the samples are taken
      from the antrum and the corpus of the stomach, this technique potentially can be
      applied routinely for the detection of this bacterium in clinical samples.

PMID- 17006403
TI  - Effects of posterior pericardiotomy on the incidence of pericardial effusion and
      atrial fibrillation after coronary revascularization.
AB  - BACKGROUND: The aim of this prospective, randomized study was to assess the
      efficacy of posterior pericardiotomy in decreasing the prevalence of pericardial
      effusion and postoperative atrial fibrillation (AF). MATERIAL/METHODS: The study
      was performed in 100 patients who underwent elective coronary artery bypass
      grafting surgery (CABG) between October 2003 and July 2005. They were randomized
      to receive posterior pericardiotomy (Group A) or no posterior pericardiotomy
      (Group B). A 4-cm longitudinal incision was made parallel and posterior to the
      left phrenic nerve, extending from the left inferior pulmonary vein to the
      diaphragm in group A patients. Posterior pericardiotomy was not performed in
      group B patients. RESULTS: Early pericardial effusion developed in 6 patients
      (12%) of group A and 21 patients (42%) of group B; no late pericardial effusion
      developed in group A, but did in 3 patients (6%) of group B. The number of
      patients who developed postoperative AF was significantly lower in the
      fenestration group compared with the control group (10% vs. 30%, p < 0.010). The
      overall incidence of supraventricular tachycardia in patients with early
      pericardial effusion was significantly higher than in patients without early
      pericardial effusion (18 patients vs. 9 patients). CONCLUSIONS: These findings
      suggest that posterior pericardiotomy reduces the prevalence of early pericardial
      effusion and related AF by improving pericardial drainage in patients undergoing
      coronary artery bypass surgery.

PMID- 17006404
TI  - The relationship of the Functional Rating Index with disability, pain, and
      quality of life in patients with low back pain.
AB  - BACKGROUND: The study was planned to determine the relationship of the Functional
      Rating Index (FRI) with disability, pain, and quality of life in patients with
      low back pain. MATERIAL/METHODS: A total of 84 patients with low back pain, of
      whom 58 were women and 26 were men, with average age of 47.8 +/- 12.0 years
      participated in this study. The Functional Rating Index was used to determine the
      functional status of the patients. Disability was evaluated using the Roland
      Morris Disability Questionnaire (RMQ), pain intensity was evaluated with the
      Visual Analog Scale (VAS), and the Short Form-36 (SF-36) was used to assess
      quality of life. The Pearson correlation coefficient was used for correlation of
      the FRI with the RMQ, VAS, and SF-36. The internal consistency for test-retest
      reproducibility of FRI was assessed with Cronbach's alpha. RESULTS: There was a
      strong positive correlation between the FRI and the RMQ (p < 0.05). It was found
      that an increase in severity of pain was associated with the FRI survey score (p
      < 0.05). There was a negative statistically significant correlation between the
      FRI and all parameters of SF-36 (p < 0.05). FRI demonstrated high internal
      consistency, with alpha = 0.960. The test-retest correlation was r = 0.926 (p =
      0.000). CONCLUSIONS: Our study reveals that the FRI, as a reliable instrument in
      assessing functional status, is associated with the RMQ, the VAS, and all items
      of the SF-36 in patients with LBP. It was concluded that changes in functional
      status were related to changes in disability, pain, and quality of life.

PMID- 17006405
TI  - Diagnostic utility of ultrasonography for respiratory distress syndrome in
      neonates.
AB  - BACKGROUND: Respiratory distress syndrome (RDS) is the most frequent cause of
      respiratory failure treated in the neonatal intensive care unit (NICU). The
      diagnosis is usually based on clinical manifestation and chest X-ray. The aim of
      the study was to investigate the possible role of chest ultrasound in the
      diagnosis of the RDS. MATERIAL/METHODS: Ultrasound examination was performed in
      131 consecutive newborns admitted to the NICU in their first day of life with
      symptoms of respiratory failure. The method of ultrasound examination of the
      chest is based on the "mirror reflection" phenomenon arising on the pulmonary
      diaphragmatic border. RESULTS: Retrohepatic or retrosplenic hyperechogenicity was
      shown in 109 of the 131 examined newborns and the diagnosis was confirmed by X
      ray in 101 cases. RDS was diagnosed in no patient without retrohepatic or
      retrosplenic hyperechogenicity. In eight patients with positive ultrasound images
      unconfirmed by chest X-ray, congenital pneumonia (four cases) and pneumothorax
      (one case) were diagnosed and in three cases no pathology was found. CONCLUSIONS:
      The ultrasound examination is characterized by 100% sensitivity and 92%
      specificity in RDS. There was a strong positive correlation between ultrasound
      and X-ray imaging in the description of RDS severity (tau = 0.835; p < 0.001).
      Ultrasound examination cannot replace chest X-ray in the respiratory failure work
      up as it overestimates the diagnosis, but it can be useful in excluding RDS as a
      cause of respiratory insufficiency in newborns.

PMID- 17006406
TI  - A case of transient central hyperthyroidism.
AB  - BACKGROUND: Thionamides are the main therapeutic arsenal for treating
      hyperthyroidism. Perhaps the first case of a patient who developed a transient
      pituitary hyperthyroidism after discontinuation of a lengthy intake of a
      thionamide is reported. CASE REPORT: A 48-year-old woman presented with menstrual
      irregularities when hypothyroidism with pituitary enlargement was detected. She
      had been undergoing treatment with methimazole for Graves's hyperthyroidism since
      the age of 34. Three months after discontinuation of methimazole she presented
      with clinical and laboratory evidence of thyrotoxicosis, with elevated thyroid
      stimulating hormone (TSH) levels and blunted response to thyrotropin releasing
      hormone (TRH). This secondary hyperthyroidism was self-limited and resolved a few
      months later. CONCLUSIONS: Chronic primary hypothyroidism caused by lengthy use
      of thionamides can result in pituitary hyperplasia and transient thyrotrope
      dysfunction.

PMID- 17006407
TI  - Malignant solitary fibrous tumor originating from the peritoneum and review of
      the literature.
AB  - BACKGROUND: Solitary fibrous tumor (SFT) is a rare neoplasm frequently involving
      the pleura. Benign and malignant forms of the tumor occur, the benign variant
      being three to four times more common than the malignant. CASE REPORT: We present
      herein a rare case of large malignant solitary fibrous tumor (SFT) originating
      from the peritoneum. An abdominal computed tomography scan revealed a well
      defined solid tumor with mixed density. An abdominal ultrasonography (US)
      revealed a well-circumscribed solid tumor containing a partially cystic lesion.
      T1-weighted abdominal magnetic resonance imaging demonstrated a hypo- to
      isointensity, which was a hypo- to hyperintensity on T2-weighted images.
      Liposarcoma originating from the retroperitoneum was suggested, and the patient
      underwent a complete resection of the tumor as well as the left kidney because
      tumor invasion of the upper left kidney was suspected. Immunohistochemically, the
      spindle-shaped cells were positive for CD34, and the diagnosis was SFT
      originating from the peritoneum. At the 14-month follow-up evaluation, no
      recurrence or metastasis was detected. CONCLUSIONS: This case gave us some
      difficulty, and the correct diagnosis of the peritoneal mass was valuable. To
      diagnose the malignant potential of this type of tumor accurately may have value
      to direct the appropriate therapeutic operations after surgery and postoperative
      progress observation.

PMID- 17006408
TI  - An unusual case of lymphedema tarda.
AB  - BACKGROUND: Lymphedema is the result of the equilibrium between the load to be
      cleared and the transport capacity of the clearing system. Lymphedema may be
      classified as primary or secondary, based on the underlying etiology. Primary
      lymphedema is an unusual disorder characterized by inadequate lymphatic drainage.
      Lymphedema tarda is a rare form of primary lymphedema. CASE REPORT: The case of
      lymphedema tarda documented here was chronic, progressive, and resistant to
      medical therapy and recurred several times after previous operations.
      CONCLUSIONS: We performed two-staged operations and we recommend that the staged
      excisional procedures offers reliable long-term improvement and minimizes
      postoperative complications in chronic advanced lymphedema.

PMID- 17006409
TI  - Morphine synthesis in animals.

PMID- 17006410
TI  - Comments to: Budd-Chiari syndrome: current options in the interventional
      radiology treatment exemplified by three selected cases.

PMID- 17006411
TI  - Occupational health services in Greek hospitals.

PMID- 17006412
TI  - Effect of yoga on somatic indicators of distress in professional computer users.

PMID- 17006413
TI  - De novo biosynthesis of morphine in animal cells: an evidence-based model.
AB  - Recent empirical findings have contributed valuable mechanistic information in
      support of a regulated de novo biosynthetic pathway for chemically authentic
      morphine in animal cells, with many similarities to the extensively characterized
      multi-enzyme plant pathway in opium poppy (Papaver somniferum). The present
      review elaborates an evidence-based model of cellular morphine expression that
      reflects a coalescence of these recent biochemical data with historical data
      gleaned from over thirty years of neurochemical/neuropharmacological
      investigation into the etiology and biological significance of dopamine (DA)
      related heterocyclic conjugate molecules, termed tetrahydroisoquinoline (TIQ) or
      benzylisoquinoline (BIQ) alkaloids, and with outstanding work completed over the
      last decade that has elucidated biochemical and molecular bases of morphine and
      related isoquinoline alkaloid expression in plant systems. In essence, we are now
      afforded a rare window of opportunity to firmly establish essential biochemical
      linkages between plant and animal biosynthetic pathways that have been conserved
      throughout evolution.

PMID- 17006414
TI  - Signaling cascades in radiation-induced apoptosis: roles of protein kinase C in
      the apoptosis regulation.
AB  - Apoptosis is a biologic mechanism for eliminating damaged cells from the cell
      population. Apoptosis is known to be induced by irradiation and can prevent the
      development of disease states such as carcinogenesis or abnormal tissue
      formation. On the other hand, if the mechanism is properly controlled,
      radiotherapy can be used to kill cancer cells more efficiently. Radiation-induced
      apoptosis is regulated by the balance between cellular anti-apoptotic and (pro
      )apoptotic signals. Many regulators of radiation-induced apoptosis have been
      identified and analyzed. Protein kinase C (PKC) is a family of serine/threonine
      kinases and one of the regulators in radiation-induced apoptosis. PKC has some
      subtypes, each of whose functions has been analyzed in radiation-induced
      signaling cascades. It has been demonstrated that each of PKC subtypes has
      distinct functions in radiation-induced apoptosis. Moreover, some participants in
      PKC-related signaling cascades have been identified in radiation-induced
      apoptosis. Interestingly, PKC-related signaling cascades have been found to be
      regulated in part by ATM (the gene that is mutated in the human genetic disorder
      ataxia telangiectasia). ATM is a protein related to cell-cycle checkpoints and
      cell radiosensitivity, and it also regulates radiation-induced apoptosis. This
      article reviews recent developments in the understanding of radiation-induced
      apoptosis, focusing on PKC functions, and the relationship with ATM.

PMID- 17006415
TI  - The inflammatory response: an efficient way of life.
AB  - The successive pathophysiological mechanisms that develop in the interstitium of
      tissues when these undergo acute post-traumatic inflammation are considered
      increasingly complex trophic functional systems for using oxygen. The nervous or
      immediate functional system presents ischemia-revascularization and edema, which
      favor nutrition by diffusion through injured tissue. In this phase of the
      inflammatory response, while the progression of the interstitial edema produces
      progressive distancing of the epithelial cells from the capillaries, it
      simultaneously enhances lymphatic circulation, which assumes an unusually
      important role. During immune system function, tissue nutrition is carried out by
      leukocytes through symbiosis with bacteria. Improper use of oxygen persists in
      this immune phase. Activated phagocytes would require anaerobic glycolysis as the
      main source of ATP for their functions. During this immune phase, lymphatic
      circulation still plays a major role. The dilatation of lymphatics may be
      mediated by cytokines, leuokotrienes, and prostaglandins produced at the trauma
      site by activated resident and infiltrating cells. Finally, the endocrine
      functional system facilitates the arrival of oxygen, transported by red blood
      cells and capillaries. Their trophic potential permits the tissue specialization
      required for tissue repair to take place. However, if complications occur during
      the evolution of acute inflammation, the tissues could go back to using more
      primitive trophic mechanisms. In summary, the ability of the interstitial tissue
      to express increasingly complex nutritional systems in relation to oxygen use
      could reflect the importance of this space as a battleground for inflammation
      and, as a result, for evolution.

PMID- 17006416
TI  - Pesticides may be altering constitutive nitric oxide release, thereby
      compromising health.
AB  - Numerous studies, focusing on the effects of environmental pollutants such as
      pyrethroids, organochlorines, organophosphate pesticides, etc, appear to affect
      intracellular ion balance, particularly calcium. We speculate that these
      chemicals may specifically target constitutive nitric oxide synthase (cNOS)
      mediated processes, e.g., immune. The alteration of intracellular Ca2+ transients
      by these pollutants may represent an important common mechanism responsible for
      the abrogation of cNOS activation. Moreover, one can hypothesize that exposure to
      sublethal levels of pesticides that alter calcium transients, could potentially
      lead to immune, neural and vascular dysfunction in animals. This may be
      especially true for marine organisms that can be found close to shore and in
      estuaries, which are more likely to be exposed to these compounds resulting from
      riverine and other inputs.

PMID- 17006417
TI  - SIAARTI recommendations for analgo-sedation in intensive care unit.

PMID- 17006418
TI  - Continuous intrathecal baclofen administration by a fully implantable electronic
      pump for severe spasticity treatment: our experience.
AB  - AIM: With this 8-month study, we wanted to evaluate the efficacy of continuous
      intrathecal baclofen infusion delivery by a programmable pump for severe
      spasticity according to patient selection criteria, implantation technique and
      related parameters, and outcome after the initial follow-up period. METHODS:
      Intrathecal baclofen infusion was initiated in 30 patients within 24 h after a
      test dose of the agent resulted positive in spinal anaesthesia. During the
      procedure and the follow-up period, the following parameters were measured:
      incidence of anaesthesiological or surgical complications and adverse events,
      postdural puncture headache, prolonged motor block, difficulty in wound healing,
      infection, necessity to remove the pump; clinical response as measured on the
      Ashworth and spasms scales, quality of sleep, autonomy, quality of life and pain
      before and after intrathecal baclofen therapy. RESULTS: Perioperative vital
      parameters (mean duration of the operation, 86+/-13 min) were stable; no motor
      block or postdural puncture headache, early or late infection developed. The 1
      case of delayed wound healing resolved with treatment; a dislocated catheter was
      repositioned in 1 other case. The differences in changes between pre- and
      posttreatment were statistically significant, with best results obtained on
      rigidity and pain. The mean length of hospital stay was 8+/-2 days. Baclofen
      tolerance was observed in 1 case, but resolved after baclofen holiday with
      morphine. One case of pump malfunctioning was resolved with replacement of the
      device; no new neurological deficits occurred thereafter. CONCLUSIONS: The good
      clinical response to treatment of spasticity and rigidity, improved quality of
      life, pain reduction and patient satisfaction with short length of admission
      demonstrate the efficacy of intrathecal baclofen therapy. Safe and efficacious,
      this mode of treatment appears to be the gold standard for treating severe
      spasticity.

PMID- 17006419
TI  - Sevoflurane as a single anesthetic and physostigmine failure to enhance arousal.
AB  - AIM: Sevoflurane is recommended for inhalational induction of anesthesia.
      Physostigmine may antagonize general anesthetics. The study investigates
      sevoflurane as a single anesthetic and its possible antagonism by physostigmine.
      METHODS: In 60 women scheduled for breast lump excision, anesthesia was induced
      with 8% sevoflurane. After 3 min of sevoflurane inhalation, a laryngeal mask
      airway (LMA) was inserted. Anesthesia was maintained with spontaneous ventilation
      at end tidal sevoflurane 3%. Systolic and diastolic blood pressure, heart rate
      and end tidal CO(2) were recorded intraoperatively. After skin closure and at end
      tidal sevoflurane 0.9%, physostigmine 2 mg or normal saline was given. After 2
      min systolic, diastolic blood pressure, heart rate and end tidal CO(2) were
      recorded and sevoflurane was discontinued. Time to eyes opening, LMA removal and
      verbal response was recorded. Patients were also assessed for orientation,
      sedation, sitting ability and the ''picking up matches'' test at 0, 15 and 30 min
      after LMA removal. RESULTS: Systolic, diastolic blood pressure and heart rate
      increased after laryngeal mask placement (P=0.0001, P=0.0001 and P=0.0001,
      respectively). Orientation, sitting ability and ''picking up'' matches were
      similar in the 2 groups. Sedation at 15 min was less in the control group
      (P=0.004). CONCLUSIONS: Sevoflurane can be used as a single anesthetic but its
      recovery is not enhanced by physostigmine.

PMID- 17006420
TI  - Anesthesiological management and outcome of 100 ''beating heart'' coronary artery
      bypass grafting.
AB  - AIM: The aim of this paper is to describe the anesthesiological management and
      the outcome of beating heart revascularization. METHODS: A prospective study has
      been performed in a tertiary teaching hospital on 100 consecutive patients
      undergoing off-pump coronary artery revascularization. The main features of
      anesthetic technique are the maintenance hemodynamic stability and atrial kick.
      RESULTS: Mechanical stabilisers shunts have improved the management of these
      patients. In hospital mortality was 1%, acute myocardial infarction 3%, low
      output syndrome 2%, atrial fibrillation 16%. Only 2% of patients had acute renal
      failure, but no patient needed renal replacement treatment. No neurologic event
      was noted. Only 19% of patients received blood transfusion. Ninety-seven % of
      patients were extubated within 12 h. CONCLUSIONS: The application of this
      anesthetic strategy combined with surgical skillful and new devices makes off
      pump surgery safe also in high risk patients.

PMID- 17006421
TI  - Short-course monotherapy strategy for treating bacteremia in the critically ill.
AB  - AIM: Routine practice in the ICU of University College London (UCL) Hospitals is
      to use short course (5-6 days) monotherapy, unless contraindicated (e.g.
      endocarditis, osteomyelitis). The aim of this study is to assess our policy by
      monitoring the clinical response, relapse rate and patient outcome. METHODS: A
      prospective observational study was carried out from February to July 2000.
      Clinically significant bacteraemia was identified by daily prospective
      surveillance of all positive blood cultures. On all the patients we recorded: 1)
      demographics; 2) antibiotic therapy (type, duration) and ACCP/SCCM sepsis
      criteria; 3) ICU support techniques (e.g. mechanical ventilation, intravascular
      catheter changes); 4) development of further bacteraemia or relapses. For all
      positive results, Gram stain, identification and antibiotic sensitivity patterns
      were noted. SPSS software was used for statistical analyses. RESULTS: Out of 713
      admitted to the ICU over the study period, 84 (8.2%) patients experienced 102
      bacteraemic episodes: 14 community-, 28 hospital- and 60 ICU-acquired (occurring
      in 49 patients). A total of 78 (76.4%) episodes [8 (57%) community-, 22 (79%)
      hospital- and 48 (80%) ICU-acquired] were treated with short course monotherapy.
      Moreover a low rate (23.8%) of death directly related to the bacteraemia and a
      satisfactory (72%) clinical response were recorded. ICU-acquired multidrug
      resistant Gram-negative bacteraemias (6.5%) and fungaemias (3%) were also
      uncommon. No patient discharged from the ICU, subsequently developed either
      bacteraemia relapse, or any long-term related complication. CONCLUSIONS: Short
      course antibiotic monotherapy strategy appears to provide a satisfactory clinical
      response, low relapse rate and no long-term infectious complications. Multicentre
      studies are warranted to confirm the efficacy of our practice.

PMID- 17006422
TI  - Endoscopic management of endometriosis.
AB  - Randomized clinical trials in the effectiveness of laparoscopic surgery in the
      management of endometriosis associated with chronic pelvic pain show a 66% to 80%
      response rate. There is a 20% to 30% ''placebo'' response rate. The value of
      surgery for infertile patients with minimal and mild disease is still debated but
      is most likely small. In advanced disease, surgery clearly improves outcome,
      although the surgery is more challenging. After an initial unsuccessful surgery
      for restoration of fertility in patients with advanced endometriosis, in vitro
      fertilization rather than repeat surgery is more effective. Laparoscopic
      treatment of endometriomas should be performed by excisional surgery. Drainage
      and/or medical therapy is associated with a very high recurrence rate. The main
      concern with excision of endometriomas is the potential to decrease ovarian
      reserve. Most experts would agree that if there is an endometrioma of 4 cm or
      greater that a laparoscopic excision be performed before an anticipated in vitro
      fertilization cycle to decrease the potential risk of infection and improve
      access to follicle. Surgery for pelvic extragenital disease is challenging.
      Excision of rectal endometriosis may require disc excision of the nodular lesion
      or segmental resection. Morbidity of a laparoscopic procedure is similar to
      laparotomy. Relief of symptoms after laparoscopic bowel surgery is excellent but
      there are potential complications such as rectovaginal fistula and pelvic
      abscess. Endo-metriosis of the bladder or ureter typically only involves the
      overlying peritoneum and can be easily excised by laparoscopy. Excision of deeper
      lesions of the bladder and ureter require resection. This can be accomplished
      laparoscopically but requires experience with laparoscopic suturing.

PMID- 17006423
TI  - [Laparoscopic hysterectomy in the management of endometrial cancer].
AB  - Endometrial carcinoma is the most commonly reported gynaecologic malignancy in
      industrialized countries. Traditionally the surgical treatment of endometrial
      cancer is total abdominal hysterectomy, bilateral salpingo-oophorectomy, and
      peritoneal washing cytology. Alternative surgical procedures have been proposed
      compared to abdominal hysterectomy: increased number of issues about laparoscopy
      shows the common trend to use this technique. Literature largely described
      advantages of the laparoscopic procedure compared to abdominal and vaginal
      surgery. Long-term follow-up series are not available; further investigation into
      survival and recurrence rates is indicated.

PMID- 17006424
TI  - [Laparoscopic treatment of adnexal cystic masses].
AB  - Operative laparoscopy has become the gold standard for the surgical treatment of
      numerous gynecological benign conditions. In the case of ovarian cysts, however,
      the use of the laparoscopic approach has been debated due to the possibility of
      encountering an unexpected ovarian malignancy at the time of surgery. This would
      upstage a IA or IB ovarian malignancy to IC. In this review, the authors evaluate
      the preoperative parameters that could help in the selection of the patients who
      are candidate to a laparoscopic approach. In particular, the authors consider the
      age related risk of the patients, the use of sonography and color-Doppler
      velocimetry, the use of CA 125, and as a last diagnostic step, the findings at
      laparoscopy. In a personal series of 1.584 cysts in patients under 40 years of
      age, the first author encountered 7 unexpected borderline tumors and 1 mucinous
      G1 adenocarcinoma, while no malignancy was found in a group of strictly selected
      postmenopausal patients. These data have been compared with those found in
      scientific literature. There is no sound evidence that the stripping procedure
      determines a reduction of the ovarian reserve when performed with strict
      microsurgical principles. Recent evidence in the literature suggests that the
      decreased ovarian responsiveness reported by some authors following ovarian
      cystectomy may not be a consequence of surgery. The concern of a possible
      reduction of the ovarian reserve needs to be balanced with the benefits obtained
      with surgery. Finally, it should always be kept in mind the risk of an unexpected
      malignancy, even in cysts apparently benign, malignancy that can only be
      diagnosed through surgery obtaining a specimen for pathology.

PMID- 17006425
TI  - Laparoscopic surgery for pelvic organ prolapse.
AB  - There is growing interest in laparoscopic procedures for the correction of pelvic
      organ prolapse. The goals of prolapse surgery are to correct symptomatic pelvic
      floor defects and reestablish vaginal support resulting in the maintenance or
      restoration of normal visceral and sexual function. A thorough understanding of
      pelvic floor support as well as anterior abdominal wall and intra-abdominal,
      pelvic, and retropubic anatomy must be ascertained before attempting laparoscopic
      prolapse procedures. As many of these procedures require advanced laparoscopic
      skills and experienced surgeons, most of the literatures are comprised of case
      series by expert surgeons, with many of the studies centered on sacral
      colpopexies. However, the principles of laparoscopic prolapse surgery are based
      on open procedures and the only difference in the technique should be related to
      the route of operation; therefore, the efficacy of laparoscopic prolapse
      procedures should theoretically be comparable to their open abdominal
      counterparts.

PMID- 17006426
TI  - The position of neoadjuvant chemotherapy within the treatment of ovarian cancer.
AB  - It is clear that primary debulking remains the standard of care within the
      treatment of advanced ovarian cancer (International Federation of Gynaecology and
      Obstetrics, FIGO, stage III and IV). Debulking surgery should be performed by a
      gynaecologic oncologist without any residual tumour load, or so called optimal
      debulking'. Over the last decades, interest in the use of neoadjuvant
      chemotherapy together with an interval debulking has increased. Open laparoscopy
      is probably the most valuable tool for evaluating the operability primarily or at
      the time of interval debulking surgery. Neoadjuvant therapy can be used for
      patients that are primarily suboptimally debulked due to an extensive tumor load.
      In this situation, based on the randomized EORTC-GCG trial, interval debulking by
      an experienced surgeon improves survival in some patients who did not undergo
      optimal primary debulking surgery. Based on the GOG 152 data, interval debulking
      surgery does not seem to be indicated in patients who underwent primarily a
      maximal surgical effort by a gynecological oncologist. Neoadjuvant chemotherapy
      can also be used as an alternative to primary debulking. In retrospective
      analyses neoadjuvant chemotherapy followed by interval debulking surgery does not
      seem to worsen prognosis compared to primary debulking surgery followed by
      chemotherapy. However, we will have to wait for the results of future randomized
      trials to know whether neoadjuvant chemotherapy followed by interval debulking
      surgery is a good alternative to primary debulking surgery in stage IIIc and IV
      patients.

PMID- 17006427
TI  - [Laparoscopic promontal fixation: assessment of 100 cases].
AB  - AIM: Aim of the study is to evaluate long term results of 100 patients treated
      laparoscopically to repair genital prolapse and urinary incontinence. METHODS: A
      retrospective review analysis of 100 women, who underwent laparoscopic genital
      prolapse repair at Primary Referral University Hospital in Clermont-Ferrand.
      Patients characteristics, preoperatory exams, intraoperative, postoperative and
      outpatient clinic data were collected and analyzed. RESULTS: The mean operative
      time was 172 minutes. One laparotomy conversion was required, due to a technical
      problem. The mean hospitalization stay was 4.7 days. Two patients required a
      reintervention during their hospitalization stay, due to a complication. All the
      patients were reviewed during the 6 months later the intervention. The follow-up
      is between 6 months and 3 years. The average degree of cystocele and hysterocele
      was ameliorated from stage 3 to stage 0, the average stage of rectocele was
      ameliorated from stage 2 to stage 0, finally the average stage of vault prolapse
      was ameliorated from stage 1 to stage 0. The incidence of genuine stress
      incontinence was 47% in the preoperative time and only 4% at the long follow-up.
      We had a total 4% rate of mesh vaginal erosion. CONCLUSIONS: The laparoscopic
      sacrocolpopexy is an effective and safe technique to repair the major pelvic
      prolapses.

PMID- 17006428
TI  - Vascular endothelial growth factor (VEGF): can we use it as prognostic factor in
      endometrial cancer?
AB  - AIM: The aim of the study was to investigate if VEGF levels reflect the severity
      of endometrial cancer and the clinic relationship between microvasal density
      (MVD) and concentration of VEGF in tumor. METHODS: The study was conducted on 22
      patients affected by endometrial cancer who were submitted to total abdominal
      radical hysterectomy plus bilateral salpingo-ophorectomy. VEGF (pg/mL) and MVD
      values were measured on histologic specimens of endometrial cancer obtained
      during the surgical treatment. The means and standard deviations of estimated
      values were calculated and a statistical comparison was effected by student t
      test for not coupled data. Pearson correlation test was used to analyze the
      eventual correlation among VEGF and MVD values in overall patients. RESULTS: We
      have documented that VEGF expression and MVD change according to FIGO stage,
      lympho-vascular infiltration and lymph node involvement. Pearson correlation test
      shows a good linear positive correlation in overall patients between VEGF and MVD
      values. CONCLUSIONS: Results obtained show a possible use of VEGF as prognostic
      factor in endometrial cancer. Confirmation of these data may permit both to
      identify high-risk patients, who must be treated with a more aggressive
      treatment, and to use an angiogenic therapy in endometrial cancer.

PMID- 17006429
TI  - [Hypercoagulability during pregnancy: evidences for a thrombophilic state].
AB  - AIM: The development of thrombotic disorders is a major threat for young women
      during pregnancy. It is one of the main causes of pregnancy-related disorders,
      which may also result in harm for the conceptus. Successful pregnancies require
      an even balance of coagulation and fibrinolysis, in order to secure stabilization
      of the basal plate as well as adequate placental perfusion. Broad spectrum assays
      which measure a range of thrombin/fibrin formation in serum have become an
      established means of identifying activation of blood coagulation and/or
      fibrinolysis. There is considerable interest in the application of these assays
      to the diagnosis of other hypercoagulable states, such as thrombophilia during
      pregnancy. We investigated coagulation/fibrinolysis parameters for significant
      differences between pregnant women during their gestation (first, second and
      third trimester) with or without pregnancy loss and healthy nonpregnant women.
      METHODS: Thirty-nine pregnant women, aged 24-39 years, were studied. They were
      subdivided according to pregnancy trimester: 15 patients in the first trimester;
      13 in the second and 11 in the third. The selection of patients was carried out
      in cooperation with the Transfusion Center of the Second University of Naples in
      order to obtain a homogeneous sample group. The control group included 400
      healthy patients. Biochemical and blood coagulation tests were performed for each
      patient and the results obtained were compared with the control group. RESULTS: A
      decrease in free protein S (PS) and fibrinolysis (t-PA/PAI-1) activities and an
      increase in Factor VII, Factor VIII, prothrombin fragment 1+2 (F1+2), D-dimer (D
      dimer) were observed in pregnant women during the follow-up of gestation.
      However, there were statistical differences between the groups of women with one
      or more pregnancy loss where it was found the lowest values in t-PA and PAI and
      the highest values in FVII and F1+2. Among subjects with more than one abortion,
      coagulation/fibrinolysis derangements before the partum were more prominent. A
      significant association exists between consecutive recurrent abortions and
      pregnancy complications such as placental abruption, hypertensive disorders and
      CS. This association persists after controlling for variables considered to
      coexist with recurrent abortions. CONCLUSIONS: These findings suggest that an
      excessive hypercoagulable state is associated with the termination of pregnancy
      resulting into a moderate risk for thrombosis during the different trimesters of
      pregnancy. The follow-up of fibrinolytic markers could represent a useful
      diagnostic tool for termination of pregnancy.

PMID- 17006430
TI  - [Fetal and maternal amniocentesis complications].
AB  - AIM: The aim of this study was to estimate the incidence of complications due to
      the prenatal invasive diagnosis performed by amniocentesis at the Department of
      Prenatal Diagnosis of the Second University of Naples. METHODS: A total of 1.580
      patients who underwent amniocentesis from January 2001 to December 2003, were
      submitted to a telephone interview concerning the complications that occurred
      after the invasive diagnosis. RESULTS: Only 1.416 patients out of the total
      patients interviewed answered correctly to the questionnaire. The complications
      that occurred in the first 24 h from amniocentesis (early complications) included
      light contractions and lipothymia respectively in 8.3% and 6.7% of cases; losses
      of amniotic fluid took place in 1.06% while bleedings were observed in 0.85% of
      cases. The incidence of abortions occurred in the week following amniocentesis
      was 0.78%. Preterm labor occurred in only 6% of the patients submitted to
      amniocentesis, spontaneous labor at term in 43% and cesarean section in 51%. The
      Apgar index at birth was normal in 95.7% of cases. In the remaining 4.3%
      pathologies like hypoglycemia or respiratory distress, which promptly regressed,
      were observed. Early complications and the incidence of abortions were
      significantly and independently associated with the double needle puncture but
      not with maternal age or the placenta specimen obtained during amniocentesis.
      CONCLUSIONS: A careful observation of the technique and the protocol, as well as
      a careful selection of patients are necessary presuppositions in order to further
      decrease the occurrence of complications due to amniocentesis.

PMID- 17006431
TI  - [First abdominal access in gynecological laparoscopy: which method to utilize?].
AB  - The choice of the technique to enter the peritoneal cavity, during a laparoscopy,
      depends on a lot of variables which hinder a standardized method and, actually,
      it appears impossible to show, with certainty, the best method to choose for the
      first abdominal access in gynecological laparoscopy. The preference for one or
      another technique depends on the operator experience, school and speciality of
      the surgeon, laparoscopical upgrading and the work environment; many surgical
      techniques are not yet used due the limits and fears of some surgeons to change
      the preference in first access approaching and for the lack of operating
      versatility by a method or another one. A review of the scientific literature,
      underlines that the major problems during the first laparoscopical abdominal
      access are two, vascular and intestinal and their percentage is variable. In this
      paper we describe the large range of methods for open and closed laparoscopy and
      for direct access, that permit to perform a first abdominal laparoscopical
      access, and their major possible problems.

PMID- 17006432
TI  - [Hydronephrosis and acute renal failure in pregnant patient affected by solitary
      kidney never diagnosed before].

PMID- 17006433
TI  - The effects of low doses of delta-9 tetrahydrocannabinol on reinforcement
      processing in the risky decision-making of young healthy adults.
AB  - Research suggests that risky decision-making is sensitive to neuromodulatory
      influences acting upon corticolimbic circuitry. However, while other evidence
      attests to effects of delta-9 tetrahydrocannabinol (THC) on the activity of
      reward pathways, relatively little is known about the possible involvement of
      cannabinoid activity in risky choice. In this experiment, we examined the effects
      of a single sublingual 5 mg dose of THC on a test of risky decision-making
      (requiring choices between simultaneously presented gambles differing in their
      magnitude of gains, magnitude of losses and the probability with which these
      outcomes were delivered). Tests of non-normative decision-making involving risk
      aversion when deciding between gains and risk-seeking choices when deciding
      between losses were also included. In all, 15 healthy adults were administered 5
      mg THC and placebo in a double-blind, placebo-controlled, within-subject, cross
      over design. THC had three principal effects relative to placebo: (i) THC reduced
      choice of gambles with variable gains and losses, but increased choice of gambles
      with zero-expected value; (ii) THC reduced participants' attention towards losses
      when the probability of winning was low (and the probability of losing was high);
      and (iii) THC speeded participants' responses to gambles with large compared to
      small potential gains. These results suggest that THC mediates specific
      motivational processes and the processing of reinforcement cues during risky
      choice, perhaps reflecting altered CB1 receptor or catecholamine activity within
      corticolimbic pathways.

PMID- 17006434
TI  - Linking data to models: data regression.
AB  - Mathematical models are an essential tool in systems biology, linking the
      behaviour of a system to the interactions between its components. Parameters in
      empirical mathematical models must be determined using experimental data, a
      process called regression. Because experimental data are noisy and incomplete,
      diagnostics that test the structural identifiability and validity of models and
      the significance and determinability of their parameters are needed to ensure
      that the proposed models are supported by the available data.

PMID- 17006435
TI  - Association between PM2.5 and all-cause and specific-cause mortality in 27 US
      communities.
AB  - While fine mode particulate matter (PM(2.5)) forms the basis for regulating
      particles in the US and other countries, there is a serious paucity of large
      population-based studies of its acute effect on mortality. To address this issue,
      we examined the association between PM(2.5) and both all-cause and specific-cause
      mortality using over 1.3 million deaths in 27 US communities between 1997 and
      2002. A two-stage approach was used. First, the association between PM(2.5) and
      mortality in each community was quantified using a case-crossover design. Second,
      meta-analysis was used to estimate a summary effect over all 27 communities.
      Effect modification of age and gender was examined using interaction terms in the
      case-crossover model, while effect modification of community-specific
      characteristics including geographic location, annual PM(2.5) concentration above
      15 microg/m(3) and central air conditioning prevalence was examined using meta
      regression. We observed a 1.21% (95% CI 0.29, 2.14%) increase in all-cause
      mortality, a 1.78% (95% CI 0.20, 3.36%) increase in respiratory related mortality
      and a 1.03% (95% CI 0.02, 2.04%) increase in stroke related mortality with a 10
      microg/m(3) increase in previous day's PM(2.5). The magnitude of these
      associations is more than triple that recently reported for PM(10), suggesting
      that combustion and traffic related particles are more toxic than larger sized
      particles. Effect modification occurred in all-cause and specific-cause deaths
      with greater effects in subjects >or=75 years of age. There was suggestive
      evidence that women may be more susceptible to PM(2.5) effects than men, and that
      effects were larger in the East than in the West. Increased prevalence of central
      air conditioning was associated with a decreased effect of PM(2.5). Our findings
      describe the magnitude of the effect on all-cause and specific-cause mortality,
      the modifiers of this association, and suggest that PM(2.5) may pose a public
      health risk even at or below current ambient levels.

PMID- 17006436
TI  - Inhalation exposure and risk from mobile source air toxics in future years.
AB  - Modeling of inhalation exposure and risks resulting from exposure to mobile
      source air toxics can be used to evaluate impacts of reductions from control
      programs on overall risk, as well as changes in relative contributions of
      different source sectors to risk, changes in contributions of different
      pollutants to overall risk, and changes in geographic distributions of risk. Such
      analysis is useful in setting regulatory priorities, and informing the decision
      making process. In this paper, we have conducted national-scale air quality,
      exposure, and risk modeling for the US in the years 2015, 2020, and 2030, using
      similar tools and methods as the 1999 National-Scale Air Toxics Assessment. Our
      results suggest that US Environmental Protection Agency emission control programs
      will substantially reduce average inhalation cancer risks and potential noncancer
      health risks from exposure to mobile source air toxics. However, cancer risk and
      noncancer hazard due to inhalation of air toxics will continue to be a public
      health concern.

PMID- 17006437
TI  - Is the midnight-to-midnight average concentration of pollutants an appropriate
      exposure index for a daily mortality study?
AB  - Midnight-to-midnight average pollutant concentration has been widely used as the
      exposure index in many epidemiological studies. This index, however, does not
      take account of the variability of time of death, because it simply takes 24-h
      average concentration from midnight to midnight, and this is equivalent to
      assuming that all deaths happened at the end of the day. This assumption is
      clearly inappropriate in the real situation, and might be a significant
      information bias in the exposure assessment. In order to take account of the
      variability of time of death, a new exposure index, the number-of-death-weighted
      24-h average, is introduced in this study. This new index is calculated for each
      subject by taking 24-h average concentration preceding the time of death. In this
      study, this new index is applied to the suspended particulate matter (SPM)
      exposure assessment in Japan, and compared with the result obtained from the
      conventional index, the midnight-to-midnight average. There are quite large
      differences in the SPM average concentration between these two indices. Moreover,
      risk ratio calculated by the new index at time lag 0, where the mortality data
      and the average concentration data on the same day are used, is a lot larger than
      that obtained by the conventional one. In addition to the difference in its
      magnitude, time lag structure (from 1-5 days) also shows the different patterns
      between these two indices. This study suggests that the conventional exposure
      index, the midnight-to-midnight average, may evaluate the risk of SPM
      incorrectly, because of its inadequacy of capturing the temporal variability.

PMID- 17006438
TI  - Di-n-butylphthalate and butylbenzylphthalate - urinary metabolite levels and
      estimated daily intakes: pilot study for the German Environmental Survey on
      children.
AB  - We analysed urine samples from the 2001/2002 pilot study of the German
      Environmental Survey on Children (GerES IV) for the concentrations of the di-n
      butylphthalate (DnBP) metabolite mono-n-butylphthalate (MnBP) and the
      butlybenzylphthalate (BBzP) metabolite mono-benzyl-phthalate (MBzP). The study
      population consisted of 239 children (106 boys, 133 girls) aged between 2 and 14
      years (median 8.5 years). We applied two calculation models to estimate the daily
      intake for the two parent phthalates from metabolite excretion. One was based on
      the creatinine-related metabolite concentrations; the other was based on the
      volume-related metabolite concentrations. Median urinary metabolite
      concentrations were 174 microg/l (136 microg/g creatinine) for MnBP and 19.7
      microg/l (15.3 microg/g creatinine) for MBzP. Such levels have been determined in
      German children before. Compared to the USA, German median MnBP levels were about
      3-10 times higher, whereas MBzP levels were in the same range. Median daily
      intakes calculated with the creatinine-based model were 4.07 (range: 0.66-76.4;
      95th percentile: 14.9) microg/kg body weight (bw)/day for DnBP and 0.42 (range:
      0.06-13.9; 95th percentile: 2.57) microg/kg bw/day for BBzP. Daily intakes
      calculated with the volume-based model were approximately two times higher with a
      median of 7.61 (range: 0.91-110; 95th percentile: 30.5) microg/kg bw/day for DnBP
      and a median of 0.77 (range: 0.05-31.3; 95th percentile: 4.48) microg/kg bw/day
      for BBzP. Using the creatinine model, 28 (11.7%) of the 239 children exceeded the
      TDI for DnBP of 10 microg/kg bw/day defined by the European Union. Employing the
      volume model, 89 (37.2%) children exceeded the TDI. For BBzP, no preventive limit
      values (TDI or RfD) were exceeded. For both phthalates and independent of the
      model, we found increasing daily intakes with decreasing age. Between 25%
      (creatinine model) and 50% (volume model) of the 2-4-year old children had daily
      intakes for DnBP above the TDI.

PMID- 17006439
TI  - In vivo effects of corticotropin-releasing hormone on femoral adipose tissue
      metabolism in women.
AB  - OBJECTIVE: To investigate whether i.v. injected corticotropin-releasing hormone
      (CRH) (1 microg/kg) has a direct effect on adipose tissue metabolism in humans.
      DESIGN: Double-blinded, placebo-controlled, crossover study. SUBJECTS: Twelve
      healthy normal weight female volunteers (age 20-37 years, body mass index:
      22.75+/-1.33 kg/m(2)) MEASUREMENTS: Assessment of local generation of glycerol,
      and glucose in adipose tissue by microdialysis. Measurement of adipose tissue and
      skin blood flow by laser Doppler flowmetry. RESULTS: Injection of CRH acutely
      increases interstitial concentrations of glycerol (19.0+/-5.4%, P<0.05) and
      glucose (13.5+/-5.8%, P<0.05) reaching peak levels after 15 min. Plasma glycerol
      increases in parallel (Delta=16.7+/-5.9% after 15 min (P<0.05)), whereas plasma
      glucose remains unaffected. Changes in tissue blood flow do not explain
      interstitial metabolite alterations. Initial CRH effects on adipose tissue
      metabolism are short lasting and disappear after 15 min. CONCLUSIONS: The
      importance of CRH on human energy metabolism is underlined by the present in vivo
      study demonstrating peptidergic effects on lipolysis and glucose homeostasis in
      human subcutaneous adipose tissue.

PMID- 17006440
TI  - Physiologic correlates of dyspnea in patients with morbid obesity.
AB  - OBJECTIVE: Mechanisms of dyspnea in obesity remain unclear. This study was
      undertaken to determine the relationships between dyspnea and pulmonary function
      including inspiratory muscle endurance (IME) in morbidly obese patients before
      bariatric surgery. RESEARCH METHODS AND PROCEDURES: Fifty-five patients with a
      mean+/-s.d. body mass index (BMI) of 49.4+/-7.0 kg/m(2) were included. Dyspnea
      was evaluated by the Baseline Dyspnea Index (BDI; 0-12, 0=maximal dyspnea).
      Pulmonary function tests included a plethysmography, maximal inspiratory pressure
      (PImax) and IME was assessed by the incremental threshold loading test,
      determining the maximal pressure sustained for 2 min (Plim(2)) and Plim(2)/PImax
      ratio. Patients were classified according to their BMI in two groups: BMI < or
      =49 (n=27) and >49 kg/m(2) (n=28). RESULTS: Breathlessness was higher in the BMI
      >49 kg/m(2) group compared to the BMI < or =49 kg/m(2) group (BDI score at 6.9+/
      2.2 in the BMI >49 kg/m(2) group vs 8.9+/-2.5 in the BMI < or =49 kg/m(2) group,
      P<0.01). Patients with BMI >49 kg/m(2) had significantly higher PaCO(2) level and
      significantly lower vital capacity, inspiratory capacity and PImax values
      compared with the BMI < or =49 kg/m(2) group. Correlations between BDI and lung
      function were moderate: forced expiratory volume in 1 s (FEV(1))% pred: Rho=0.27;
      P=0.05; vital capacity % pred: Rho=0.40; P=0.004; and Plim(2)/PImax: Rho=0.40;
      P=0.003. Higher correlations with dyspnea were found in the BMI < or =49 kg/m(2)
      group: FEV(1)% pred: Rho=0.38; P=0.05; and Plim(2)/PImax: Rho=0.49; P=0.01.
      DISCUSSION: Inspiratory muscle performance is moderately reduced in morbid
      obesity. Dyspnea in these patients remains moderately related to lung function
      and inspiratory muscle performance. However, inspiratory muscles performance
      correlates more significantly with dyspnea in patients with a BMI < or =49
      kg/m(2).

PMID- 17006441
TI  - Self-selection contributes significantly to the lower adiposity of faster, longer
      distanced, male and female walkers.
AB  - OBJECTIVE: Cross-sectional studies show that active individuals are leaner than
      their sedentary counterparts. The purpose of this paper is to determine the
      extent that this is due to self-selection bias, specifically to initially leaner
      men and women choosing to exercise longer and more intensely. METHODS: Walking
      quantity (weekly distance) and intensity (speed) were compared to current body
      mass index (BMI) (BMI(current)) and BMI at the start of walking (BMI(starting))
      in 20,353 women and 5174 men who on average had walked regularly for exercise for
      7.2 and 10.6 years, respectively. RESULTS: The relationships of both BMI(current)
      and BMI(starting) to both distance and intensity were nonlinear (convex). On
      average, BMI(starting) explained >70% of the association between BMI(current) and
      intensity, and 40 and 17% of the associations between BMI(current) and distance
      in women and men, respectively. Although the declines in BMI(current) with
      distance and intensity were greater among fatter individuals than leaner
      individuals, the portions attributable to BMI(starting) remained relatively
      constant regardless of fatness. Thus, self-selection bias accounted for most of
      the decline in BMI with walking intensity and smaller, albeit significant,
      proportions of the decline with distance. CONCLUSION: Although walking intensity
      and walking distance are both strongly associated with greater leanness,
      intensity is less likely to be causally related to leanness than is distance, and
      the latter should be encouraged for reversing or preventing weight gain.

PMID- 17006442
TI  - Treatment of morbid obesity by intraparietogastric administration of botulinum
      toxin: a randomized, double-blind, controlled study.
AB  - OBJECTIVE: The stomach is the main target organ for bariatric surgery, but no
      medical treatment has been developed to increase satiety and decrease food intake
      via gastric pathways. The aim of our study was to investigate whether or not the
      intraparietogastric administration of botulinum toxin A (BTX), able to modify the
      motility patterns of the stomach, could be useful for treatment of obesity.
      DESIGN: Double blind controlled study. SUBJECTS: Twenty-four morbidly obese
      patients (mean weight (s.e.m.) 116.1+/-4.89 kg, mean body mass index (BMI) 43.6+/
      1.09 kg/m(2)) were blindly randomized to receive 200 IU BTX or placebo into the
      antrum and fundus of the stomach by intraparietal endoscopic administration.
      MEASUREMENTS: We evaluated weight loss, BMI changes, satiety score, the maximal
      gastric capacity for liquids and the gastric emptying time (octanoic acid breath
      test). RESULTS: The two groups were homogeneous for anthropometric
      characteristics. Eight weeks after treatment, BTX patients had significantly
      higher weight loss (11+/-1.09 vs 5.7+/-1.1 kg, P<0.001) and BMI reduction (4+/
      0.36 vs 2+/-0.58 kg/m(2), P<0.001) and a higher satiety score on a visual
      analogic scale (7.63+/-0.38 vs 4.72+/-0.44, P<0.001) than controls. Furthermore,
      BTX patients showed a significantly greater reduction in maximal gastric capacity
      for liquids (266.6+/-48 vs 139+/-31, P<0.001) and a greater prolongation in
      gastric emptying time (+18.93+/-8 vs -2.2+/-6.9 min, P<0.05). No significant side
      effects or neurophysiologic changes were found. CONCLUSIONS: Topical intragastric
      BTX was effective in reducing food intake and body weight in morbidly obese
      patients.

PMID- 17006443
TI  - The association between low physical fitness and high body mass index or waist
      circumference is increasing with age in children: the 'Quebec en Forme' Project.
AB  - OBJECTIVE: To evaluate physical fitness and body composition of children involved
      in the 'Quebec en Forme' (QEF) Project and to compare data obtained to the
      reference values of the 1981 Canada Fitness Survey (CFS). DESIGN: Cross-sectional
      study. SUBJECTS: A total of 1140 children (591 boys and 549 girls) of first (7
      years), second (8 years) and fourth (10 years) grade from primary schools in the
      City of Trois-Rivieres (Quebec) were selected to participate in this study.
      MEASUREMENTS: Body mass index (BMI) and waist circumference (WC) were measured.
      The physical fitness tests included standing long jump, 1-min speed sit-ups and
      speed shuttle run. RESULTS: The prevalence of overweight in children ranged
      between 20 and 30%, which represents a substantial increase compared to the 1981
      CFS. The relationship between BMI and WC was highly significant in boys and girls
      (r=0.90 and 0.86, respectively, P<0.0001). The negative correlations between BMI
      or WC and the performance in all physical fitness tests were mostly significant
      in children of both genders (-0.16 < or = r < or = -0.45, at least P<0.05), and
      these relationships were significantly greater in older children (P<0.05). Based
      on the 1981 CFS, only 4.7-14.1% of QEF boys still performed in the upper quartile
      of the distribution (fit boys), whereas 32.1-69% performed not much higher than
      the lower quartile (unfit boys) for each fitness test. In girls, the relative
      fitness decrease observed in 2003 was more pronounced since only 1-9.9% of
      subjects performed in the upper quartile of the distribution compared to 42.8
      81.4% who did not perform higher than the lower quartile of the 1981 reference
      scores of the CFS. CONCLUSION: This study shows that BMI and WC are negatively
      correlated with physical fitness and that these associations are more pronounced
      in older children. Furthermore, physical fitness of our cohort, especially in
      girls, was much lower than what was documented in the 1981 CFS in subjects of the
      same age. This study thus emphasizes the necessity to develop early interventions
      to improve physical fitness in children and to prevent the increase of childhood
      obesity.

PMID- 17006444
TI  - Eating habits in relation to body fatness and gender in adolescents--results from
      the 'SWEDES' study.
AB  - OBJECTIVE: To investigate if eating habits among adolescents are related to body
      fatness and gender. DESIGN: Cross-sectional study. SETTING: Obesity Unit,
      Huddinge University Hospital, Sweden, 2001-2002. SUBJECTS: Two hundred and
      seventy-five girls and 199 boys, aged 16-17 years. METHOD: Questionnaires were
      used for dietary intake and meal frequency, BodPod for measuring body fatness
      (BF%). In all, 169 girls and 128 boys were classified as adequate reporters (AR)
      of energy intake, and were used in the dietary analyses. The whole sample was
      used in the meal frequency analyses. RESULTS: The correlation between reported
      energy intake and weight in the AR group was 0.23 (P<0.01) for girls and 0.36 for
      boys (P<0.001). The correlations were inverse or not significant in the whole
      sample. The following variables correlated significantly with a high BF% (r
      (s)=+/-0.2): a low intake of milk in both girls and boys, a high intake of fibre
      and alcohol and a low intake of sugar in girls and a low intake of breakfast
      cereals in boys. Those with regular breakfast habits had healthier food choices
      than others, but this was not related to BF%. Boys had more meals per day (4.9 vs
      4.6, P=0.02), especially early in the morning and late at night, whereas girls
      reported a higher relative intake of light meals and fruit and a lower intake of
      milk than boys. CONCLUSIONS: A few associations between eating habits and body
      fatness were found, but without any obvious patterns. The true differences in
      eating habits between lean and overweight adolescents are probably very small.

PMID- 17006445
TI  - Hb A1c in relation to intrauterine growth among male adolescents in southern
      Brazil.
AB  - The fetal origins hypothesis states that nutritional deprivation in utero affects
      fetal development and contributes to the incidence of diseases associated with
      the metabolic syndrome in later life. This study investigated whether haemoglobin
      (Hb) A(1c), an indicator of blood glucose, varied among healthy male adolescents
      according to their fetal growth rate, in a middle-income setting. Participants
      were men aged 18 years, belonging to the 1982 Pelotas birth cohort. Complete
      data, including gestational age and Hb A(1c) at age 18 years, were available for
      197 individuals. There was an inverse association between mean Hb A(1c) and
      birthweight for the gestational age, but not birthweight alone. The association
      remained significant after adjustment for family income and mother's education,
      as well as for body mass index at 18 years (P for trend=0.01 and 0.03,
      respectively).

PMID- 17006446
TI  - Comparison of anthropometric, metabolic and dietary fatty acids profiles in lean
      and obese dyslipidaemic Asian Indian male subjects.
AB  - OBJECTIVES: To compare obesity measures, metabolic profiles and dietary fatty
      acids in lean and obese dyslipideamic Asian Indian male subjects. DESIGN: Cross
      sectional. SETTINGS: Asian Indians living in the eastern part of India. SUBJECTS:
      One hundred and thirty (Group I: lean control, n=50; Group II: lean
      dyslipidaemic, n=40 and Group III: obese dyslipidaemic, n=40) Asian Indian male
      subjects (> or =30 years) living in the eastern part of India. METHODS:
      Anthropometric measures namely height, weight, circumferences of waist (WC) and
      hip, lipids (total cholesterol (TC) and triglycerides (TG)), lipoproteins (high-
      (HDL) and low-density lipoproteins (LDL)), fasting plasma glucose (FPG) and
      dietary fatty acids were obtained from each participant. Obesity measures, that
      is, body mass index (BMI), waist-hip ratio (WHR) and conicity index (CI) were
      subsequently calculated from anthropometric measures. Obesity was defined as
      individuals having BMI> or =25 kg/m(2). SUBJECTS with one or more of the
      following conditions were considered as dyslipidaemic: TG> or =2.3 mmol/l, TC> or
      =6.2 mmol/l, or TC/HDL> or =4.4 mmol/l. Daily intake of nutrients as well as
      saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA)
      were estimated by adding together all the foodstuffs consumed on weekly and
      monthly manner. Conversion of foodstuffs into nutrients was performed according
      to standard nutritive values of Indian foodstuffs. RESULTS: Analysis of variance
      with Scheffe's post hoc test revealed that Group I had significantly lower mean
      compared to both Group II and Group III for age, WC, WHR, CI, TC, TG, LDL, FPG,
      total carbohydrates intake and intake of trans fatty acids. On the other hand,
      Group I had significantly lower mean than Group III only for BMI as well as
      intake of total proteins, total fats, total energy and erucic acids. Although,
      Group I had significantly greater mean compared to both Group II and Group III
      for HDL, UFA/SFA, MUFA/SFA and PUFA/SFA. Pearson's partial correlations
      (controlling for age and total energy) revealed that central obesity measures
      (WC, WHR and CI) had significant association with dietary fatty acids and their
      ratios. Furthermore, partial correlations (controlling for age) also showed that
      the ratios of unsaturated to SFA had significant negative association with
      lipids, lipoproteins (except HDL) and plasma glucose. Discriminant function
      analysis revealed that overall 78% of all entries were positively (correctly)
      classified in three groups using fatty acids and their ratios. CONCLUSION: It
      seems rational to argue that while dealing with dyslipidaemic Asian Indians,
      clinicians should consider obesity measures, metabolic profiles and dietary fatty
      acids simultaneously to better comprehend the condition (s).

PMID- 17006448
TI  - Co-evolution of transcriptional and post-translational cell-cycle regulation.
AB  - DNA microarray studies have shown that hundreds of genes are transcribed
      periodically during the mitotic cell cycle of humans, budding yeast, fission
      yeast and the plant Arabidopsis thaliana. Here we show that despite the fact the
      protein complexes involved in this process are largely the same among all
      eukaryotes, their regulation has evolved considerably. Our comparative analysis
      of several large-scale data sets reveals that although the regulated subunits of
      each protein complex are expressed just before its time of action, the identity
      of the periodically expressed proteins differs significantly between organisms.
      Moreover, we show that these changes in transcriptional regulation have co
      evolved with post-translational control independently in several lineages; loss
      or gain of cell-cycle-regulated transcription of specific genes is often mirrored
      by changes in phosphorylation of the proteins that they encode. Our results
      indicate that many different solutions have evolved for assembling the same
      molecular machines at the right time during the cell cycle, involving both
      transcriptional and post-translational layers that jointly control the dynamics
      of biological systems.

PMID- 17006449
TI  - Genomic analysis of increased host immune and cell death responses induced by
      1918 influenza virus.
AB  - The influenza pandemic of 1918-19 was responsible for about 50 million deaths
      worldwide. Modern histopathological analysis of autopsy samples from human
      influenza cases from 1918 revealed significant damage to the lungs with acute,
      focal bronchitis and alveolitis associated with massive pulmonary oedema,
      haemorrhage and rapid destruction of the respiratory epithelium. The contribution
      of the host immune response leading to this severe pathology remains largely
      unknown. Here we show, in a comprehensive analysis of the global host response
      induced by the 1918 influenza virus, that mice infected with the reconstructed
      1918 influenza virus displayed an increased and accelerated activation of host
      immune response genes associated with severe pulmonary pathology. We found that
      mice infected with a virus containing all eight genes from the pandemic virus
      showed marked activation of pro-inflammatory and cell-death pathways by 24 h
      after infection that remained unabated until death on day 5. This was in contrast
      with smaller host immune responses as measured at the genomic level, accompanied
      by less severe disease pathology and delays in death in mice infected with
      influenza viruses containing only subsets of 1918 genes. The results indicate a
      cooperative interaction between the 1918 influenza genes and show that study of
      the virulence of the 1918 influenza virus requires the use of the fully
      reconstructed virus. With recent concerns about the introduction of highly
      pathogenic avian influenza viruses into humans and their potential to cause a
      worldwide pandemic with disastrous health and economic consequences, a
      comprehensive understanding of the global host response to the 1918 virus is
      crucial. Moreover, understanding the contribution of host immune responses to
      virulent influenza virus infections is an important starting point for the
      identification of prognostic indicators and the development of novel antiviral
      therapies.

PMID- 17006450
TI  - Reassembly of shattered chromosomes in Deinococcus radiodurans.
AB  - Dehydration or desiccation is one of the most frequent and severe challenges to
      living cells. The bacterium Deinococcus radiodurans is the best known
      extremophile among the few organisms that can survive extremely high exposures to
      desiccation and ionizing radiation, which shatter its genome into hundreds of
      short DNA fragments. Remarkably, these fragments are readily reassembled into a
      functional 3.28-megabase genome. Here we describe the relevant two-stage DNA
      repair process, which involves a previously unknown molecular mechanism for
      fragment reassembly called 'extended synthesis-dependent strand annealing'
      (ESDSA), followed and completed by crossovers. At least two genome copies and
      random DNA breakage are requirements for effective ESDSA. In ESDSA, chromosomal
      fragments with overlapping homologies are used both as primers and as templates
      for massive synthesis of complementary single strands, as occurs in a single
      round multiplex polymerase chain reaction. This synthesis depends on DNA
      polymerase I and incorporates more nucleotides than does normal replication in
      intact cells. Newly synthesized complementary single-stranded extensions become
      'sticky ends' that anneal with high precision, joining together contiguous DNA
      fragments into long, linear, double-stranded intermediates. These intermediates
      require RecA-dependent crossovers to mature into circular chromosomes that
      comprise double-stranded patchworks of numerous DNA blocks synthesized before
      radiation, connected by DNA blocks synthesized after radiation.

PMID- 17006451
TI  - Sodium-dependent uptake of inorganic phosphate by the intracellular malaria
      parasite.
AB  - As the malaria parasite, Plasmodium falciparum, grows within its host erythrocyte
      it induces an increase in the permeability of the erythrocyte membrane to a range
      of low-molecular-mass solutes, including Na+ and K+ (ref. 1). This results in a
      progressive increase in the concentration of Na+ in the erythrocyte cytosol. The
      parasite cytosol has a relatively low Na+ concentration and there is therefore a
      large inward Na+ gradient across the parasite plasma membrane. Here we show that
      the parasite exploits the Na+ electrochemical gradient to energize the uptake of
      inorganic phosphate (P(i)), an essential nutrient. P(i) was taken up into the
      intracellular parasite by a Na+-dependent transporter, with a stoichiometry of
      2Na+:1P(i) and with an apparent preference for the monovalent over the divalent
      form of P(i). A P(i) transporter (PfPiT) belonging to the PiT family was cloned
      from the parasite and localized to the parasite surface. Expression of PfPiT in
      Xenopus oocytes resulted in Na+-dependent P(i) uptake with characteristics
      similar to those observed for P(i) uptake in the parasite. This study provides
      new insight into the significance of the malaria-parasite-induced alteration of
      the ionic composition of its host cell.

PMID- 17006452
TI  - Functional epistasis on a common MHC haplotype associated with multiple
      sclerosis.
AB  - Genes in the major histocompatibility complex (MHC) encode proteins important in
      activating antigen-specific immune responses. Alleles at adjacent MHC loci are
      often in strong linkage disequilibrium; however, little is known about the
      mechanisms responsible for this linkage disequilibrium. Here we report that the
      human MHC HLA-DR2 haplotype, which predisposes to multiple sclerosis, shows more
      extensive linkage disequilibrium than other common caucasian HLA haplotypes in
      the DR region and thus seems likely to have been maintained through positive
      selection. Characterization of two multiple-sclerosis-associated HLA-DR alleles
      at separate loci by a functional assay in humanized mice indicates that the
      linkage disequilibrium between the two alleles may be due to a functional
      epistatic interaction, whereby one allele modifies the T-cell response activated
      by the second allele through activation-induced cell death. This functional
      epistasis is associated with a milder form of multiple-sclerosis-like disease.
      Such epistatic interaction might prove to be an important general mechanism for
      modifying exuberant immune responses that are deleterious to the host and could
      also help to explain the strong linkage disequilibrium in this and perhaps other
      HLA haplotypes.

PMID- 17006453
TI  - Identification of a mammalian mitochondrial porphyrin transporter.
AB  - The movement of anionic porphyrins (for example, haem) across intracellular
      membranes is crucial to many biological processes, but their mitochondrial
      translocation and coordination with haem biosynthesis is not understood.
      Transport of porphyrins into isolated mitochondria is energy-dependent, as
      expected for the movement of anions into a negatively charged environment. ATP
      binding cassette transporters actively facilitate the transmembrane movement of
      substances. We found that the mitochondrial ATP-binding cassette transporter
      ABCB6 is upregulated (messenger RNA and protein in human and mouse cells) by
      elevation of cellular porphyrins and postulated that ABCB6 has a function in
      porphyrin transport. We also predicted that ABCB6 is functionally linked to haem
      biosynthesis, because its mRNA is found in both human bone marrow and CD71+ early
      erythroid cells (by database searching), and because our results show that ABCB6
      is highly expressed in human fetal liver, and Abcb6 in mouse embryonic liver.
      Here we demonstrate that ABCB6 is uniquely located in the outer mitochondrial
      membrane and is required for mitochondrial porphyrin uptake. After ABCB6 is
      upregulated in response to increased intracellular porphyrin, mitochondrial
      porphyrin uptake activates de novo porphyrin biosynthesis. This process is
      blocked when the Abcb6 gene is silenced. Our results challenge previous
      assumptions about the intracellular movement of porphyrins and the factors
      controlling haem biosynthesis.

PMID- 17006454
TI  - Alpha-interferon for relapsed non-Hodgkin's lymphoma.

PMID- 17006455
TI  - Titrating graft-versus-host disease: is it worth a try?
AB  - The optimum graft-versus-host disease (GVHD) management in today's clinical
      practice remains controversial. There is an enormous heterogeneity among
      transplanters in their therapeutic decisions for each individual patient with
      GVHD. Existing guidelines do not always cover many unique clinical scenarios.
      Consequently, a significant number of allograft recipients fail either because of
      severe GVHD or relapse of underlying malignancy. Until more effective methods are
      available, tailoring the current GVHD management by modification of
      immunosuppressive therapy in each patient based on disease and transplant
      characteristics may decrease the mortality. The purpose of this review is to
      raise several questions among readers about GVHD management and generate new
      hypotheses, which may need to be tested in cooperative group studies.

PMID- 17006456
TI  - Minimum compliance for a microarray experiment?
AB  - Results generated with the use of microarrays should be properly described and
      deposited in one of the public databases prior to review. We examine the last two
      years of the journal's publications in an attempt to ensure that community
      standards for data deposition are met.

PMID- 17006457
TI  - Many hypotheses but no replication for the association between PDE4D and stroke.

PMID- 17006459
TI  - The genetics of health.
AB  - Recent experience with several high-profile drugs demonstrates the great
      challenges in developing effective and safe therapeutics. A complementary
      approach to the popular paradigm of disease genetics is based on inherited
      factors that reduce the incidence and severity of disease among individuals who
      are genetically predisposed to disease. We propose testing specifically for
      modifier genes and protective alleles among at-risk individuals and studying the
      efficacy of therapeutics based on the genetics of health.

PMID- 17006461
TI  - Tiling DNA microarrays for fly genome cartography.

PMID- 17006462
TI  - (Re)modeling the transcriptional enhancer.

PMID- 17006463
TI  - New evidence that DNA encodes its packaging.

PMID- 17006464
TI  - A WNK in the kidney controls blood pressure.

PMID- 17006468
TI  - Plant genetics: increased outcrossing in hothead mutants.
AB  - Arising from: S. J. Lolle, J. L. Victor, J. M. Young & R. E. Pruitt 434, 505-509
      (2005); Lolle et al. reply. Lolle et al. report that loss-of-function alleles of
      the HOTHEAD (HTH) gene in Arabidopsis thaliana are genetically unstable, giving
      rise to wild-type revertants. On the basis of the reversion of many other genetic
      markers in hth plants, they suggested a model in which a cache of extragenomic
      information could cause genes to revert to the genotype of previous generations.
      In our attempts to reproduce this phenomenon, we discovered that hth mutants show
      a marked tendency to outcross (unlike wild-type A. thaliana, which is almost
      exclusively self-fertilizing). Moreover, when hth plants are grown in isolation,
      their genetic inheritance is completely stable. These results may provide an
      alternative explanation for the genome wide non-mendelian inheritance reported by
      Lolle et al.

PMID- 17006472
TI  - A German academy.

PMID- 17006473
TI  - Priorities in astronomy.

PMID- 17006474
TI  - Reforms on drug safety.

PMID- 17006476
TI  - Superconductivity research is down but not out.

PMID- 17006478
TI  - Is US hurricane report being quashed?

PMID- 17006479
TI  - Statistical flaw trips up study of bad stats.

PMID- 17006477
TI  - Stem cells derived from 'dead' human embryo.

PMID- 17006480
TI  - Snapshot: face facts.

PMID- 17006481
TI  - Mouse brain map is complete.

PMID- 17006482
TI  - Bad Boys question received wisdom on HIV.

PMID- 17006484
TI  - 'Big science' protein project under fire.

PMID- 17006487
TI  - Turbulent times.

PMID- 17006488
TI  - Decadal surveys: wishing for the stars.

PMID- 17006489
TI  - Hagia Sophia: shaken, not stirred.

PMID- 17006490
TI  - Science journalism: fighting a reporting battle.

PMID- 17006491
TI  - Piltdown wasn't cricket but does the hobbit ring true?

PMID- 17006492
TI  - Funders with money to spare could just pay more.

PMID- 17006493
TI  - Challenge of choosing right level of microarray detail.

PMID- 17006494
TI  - Hungary's 'reforms' are threatening basic science.

PMID- 17006501
TI  - Chemistry: hydrogen at the flick of a switch.

PMID- 17006500
TI  - Ecology: a pitcher of things to come.

PMID- 17006502
TI  - Evolution: different paths to the same end.

PMID- 17006503
TI  - Condensed-matter physics: coherent questions.

PMID- 17006504
TI  - Climate change: a nasty surprise in the greenhouse.

PMID- 17006505
TI  - Biomaterials: silk-like secretion from tarantula feet.
AB  - An unsuspected attachment mechanism may help these huge spiders to avoid
      catastrophic falls. Spiders spin silk from specialized structures known as
      abdominal spinnerets--a defining feature of the creatures--and this is deployed
      to capture prey, protect themselves, reproduce and disperse. Here we show that
      zebra tarantulas (Aphonopelma seemanni) from Costa Rica also secrete silk from
      their feet to provide adhesion during locomotion, enabling these spiders to cling
      to smooth vertical surfaces. Our discovery that silk is produced by the feet
      provides a new perspective on the origin and diversification of spider silk.

PMID- 17006506
TI  - Bose-Einstein condensation of exciton polaritons.
AB  - Phase transitions to quantum condensed phases--such as Bose-Einstein condensation
      (BEC), superfluidity, and superconductivity--have long fascinated scientists, as
      they bring pure quantum effects to a macroscopic scale. BEC has, for example,
      famously been demonstrated in dilute atom gas of rubidium atoms at temperatures
      below 200 nanokelvin. Much effort has been devoted to finding a solid-state
      system in which BEC can take place. Promising candidate systems are semiconductor
      microcavities, in which photons are confined and strongly coupled to electronic
      excitations, leading to the creation of exciton polaritons. These bosonic quasi
      particles are 10(9) times lighter than rubidium atoms, thus theoretically
      permitting BEC to occur at standard cryogenic temperatures. Here we detail a
      comprehensive set of experiments giving compelling evidence for BEC of
      polaritons. Above a critical density, we observe massive occupation of the ground
      state developing from a polariton gas at thermal equilibrium at 19 K, an increase
      of temporal coherence, and the build-up of long-range spatial coherence and
      linear polarization, all of which indicate the spontaneous onset of a macroscopic
      quantum phase.

PMID- 17006507
TI  - Evolution of alternative transcriptional circuits with identical logic.
AB  - Evolution of gene regulation is an important contributor to the variety of life.
      Here, we analyse the evolution of a combinatorial transcriptional circuit
      composed of sequence-specific DNA-binding proteins that are conserved among all
      eukaryotes. This circuit regulates mating in the ascomycete yeast lineage. We
      first identify a group of mating genes that was transcriptionally regulated by an
      activator in a fungal ancestor, but is now transcriptionally regulated by a
      repressor in modern bakers' yeast. Despite this change in regulatory mechanism,
      the logical output of the overall circuit remains the same. By examining the
      regulation of mating in modern yeasts that are related to different extents, we
      deduce specific, sequential changes in both cis- and trans-regulatory elements
      that constitute the transition from positive to negative regulation. These
      changes indicate specific mechanisms by which fitness barriers were traversed
      during the transition.

PMID- 17006508
TI  - Infall of gas as the formation mechanism of stars up to 20 times more massive
      than the Sun.
AB  - Theory predicts and observations confirm that low-mass stars (like the Sun) in
      their early life grow by accreting gas from the surrounding material. But for
      stars approximately 10 times more massive than the Sun (approximately 10M(o)),
      the powerful stellar radiation is expected to inhibit accretion and thus limit
      the growth of their mass. Clearly, stars with masses >10M(o) exist, so there must
      be a way for them to form. The problem may be solved by non-spherical accretion,
      which allows some of the stellar photons to escape along the symmetry axis where
      the density is lower. The recent detection of rotating disks and toroids around
      very young massive stars has lent support to the idea that high-mass ( > 8M(o))
      stars could form in this way. Here we report observations of an ammonia line
      towards a high-mass star forming region. We conclude that the gas is falling
      inwards towards a very young star of approximately 20M(o), in line with
      theoretical predictions of non-spherical accretion.

PMID- 17006509
TI  - Bose-Einstein condensation of quasi-equilibrium magnons at room temperature under
      pumping.
AB  - Bose-Einstein condensation is one of the most fascinating phenomena predicted by
      quantum mechanics. It involves the formation of a collective quantum state
      composed of identical particles with integer angular momentum (bosons), if the
      particle density exceeds a critical value. To achieve Bose-Einstein condensation,
      one can either decrease the temperature or increase the density of bosons. It has
      been predicted that a quasi-equilibrium system of bosons could undergo Bose
      Einstein condensation even at relatively high temperatures, if the flow rate of
      energy pumped into the system exceeds a critical value. Here we report the
      observation of Bose-Einstein condensation in a gas of magnons at room
      temperature. Magnons are the quanta of magnetic excitations in a magnetically
      ordered ensemble of magnetic moments. In thermal equilibrium, they can be
      described by Bose-Einstein statistics with zero chemical potential and a
      temperature-dependent density. In the experiments presented here, we show that by
      using a technique of microwave pumping it is possible to excite additional
      magnons and to create a gas of quasi-equilibrium magnons with a non-zero chemical
      potential. With increasing pumping intensity, the chemical potential reaches the
      energy of the lowest magnon state, and a Bose condensate of magnons is formed.

PMID- 17006510
TI  - Violation of the incompressibility of liquid by simple shear flow.
AB  - In standard fluid dynamics, the density change associated with flow is often
      assumed to be negligible, implying that the fluid is incompressible. For example,
      this has been established for simple shear flows, where no pressure change is
      associated with flow: there is no volume deformation due to viscous stress and
      inertial effects can be neglected. Accordingly, any flow-induced instabilities
      (such as cavitation) are unexpected for simple shear flows. Here we demonstrate
      that the incompressibility condition can be violated even for simple shear flows,
      by taking into account the coupling between the flow and density fluctuations,
      which arises owing to the density dependence of the viscosity. We show that a
      liquid can become mechanically unstable above a critical shear rate that is given
      by the inverse of the derivative of viscosity with respect to pressure. Our model
      predicts that, for very viscous liquids, this shear-induced instability should
      occur at moderate shear rates that are experimentally accessible. Our results
      explain the unusual shear-induced instability observed in viscous lubricants, and
      may illuminate other poorly understood phenomena associated with mechanical
      instability of liquids at low Reynolds number; for example, shear-induced
      cavitation and bubble growth, and shear-banding of very viscous liquids such as
      metallic glasses and the Earth's mantle.

PMID- 17006511
TI  - Contribution of anthropogenic and natural sources to atmospheric methane
      variability.
AB  - Methane is an important greenhouse gas, and its atmospheric concentration has
      nearly tripled since pre-industrial times. The growth rate of atmospheric methane
      is determined by the balance between surface emissions and photochemical
      destruction by the hydroxyl radical, the major atmospheric oxidant. Remarkably,
      this growth rate has decreased markedly since the early 1990s, and the level of
      methane has remained relatively constant since 1999, leading to a downward
      revision of its projected influence on global temperatures. Large fluctuations in
      the growth rate of atmospheric methane are also observed from one year to the
      next, but their causes remain uncertain. Here we quantify the processes that
      controlled variations in methane emissions between 1984 and 2003 using an
      inversion model of atmospheric transport and chemistry. Our results indicate that
      wetland emissions dominated the inter-annual variability of methane sources,
      whereas fire emissions played a smaller role, except during the 1997-1998 El Nino
      event. These top-down estimates of changes in wetland and fire emissions are in
      good agreement with independent estimates based on remote sensing information and
      biogeochemical models. On longer timescales, our results show that the decrease
      in atmospheric methane growth during the 1990s was caused by a decline in
      anthropogenic emissions. Since 1999, however, they indicate that anthropogenic
      emissions of methane have risen again. The effect of this increase on the growth
      rate of atmospheric methane has been masked by a coincident decrease in wetland
      emissions, but atmospheric methane levels may increase in the near future if
      wetland emissions return to their mean 1990s levels.

PMID- 17006512
TI  - Continental-scale patterns of canopy tree composition and function across
      Amazonia.
AB  - The world's greatest terrestrial stores of biodiversity and carbon are found in
      the forests of northern South America, where large-scale biogeographic patterns
      and processes have recently begun to be described. Seven of the nine countries
      with territory in the Amazon basin and the Guiana shield have carried out large
      scale forest inventories, but such massive data sets have been little exploited
      by tropical plant ecologists. Although forest inventories often lack the species
      level identifications favoured by tropical plant ecologists, their consistency of
      measurement and vast spatial coverage make them ideally suited for numerical
      analyses at large scales, and a valuable resource to describe the still poorly
      understood spatial variation of biomass, diversity, community composition and
      forest functioning across the South American tropics. Here we show, by using the
      seven forest inventories complemented with trait and inventory data collected
      elsewhere, two dominant gradients in tree composition and function across the
      Amazon, one paralleling a major gradient in soil fertility and the other
      paralleling a gradient in dry season length. The data set also indicates that the
      dominance of Fabaceae in the Guiana shield is not necessarily the result of root
      adaptations to poor soils (nodulation or ectomycorrhizal associations) but
      perhaps also the result of their remarkably high seed mass there as a potential
      adaptation to low rates of disturbance.

PMID- 17006513
TI  - BRX mediates feedback between brassinosteroid levels and auxin signalling in root
      growth.
AB  - Brassinosteroid and auxin decisively influence plant development, and overlapping
      transcriptional responses to these phytohormones suggest an interaction between
      the two pathways. However, whether this reflects direct feedback or merely
      parallel inputs on common targets is unclear. Here we show that in Arabidopsis
      roots, this interaction is mediated by BREVIS RADIX (BRX), which is required for
      optimal root growth. We demonstrate that the brx phenotype results from a root
      specific deficiency of brassinosteroid and is due to reduced, BRX-dependent
      expression of a rate-limiting enzyme in brassinosteroid biosynthesis.
      Unexpectedly, this deficiency affects the root expression level of approximately
      15% of all Arabidopsis genes, but the transcriptome profile can be restored to
      wild type by brassinosteroid treatment. Thus, proper brassinosteroid levels are
      required for the correct expression of many more genes than previously suspected.
      Moreover, embryonic or post-embryonic brassinosteroid application fully or
      partially, respectively, rescues the brx phenotype. Further, auxin-responsive
      gene expression is globally impaired in brx, demonstrating that brassinosteroid
      levels are rate-limiting for auxin-responsive transcription. BRX expression is
      strongly induced by auxin and mildly repressed by brassinolide, which means that
      BRX acts at the nexus of a feedback loop that maintains threshold brassinosteroid
      levels to permit optimal auxin action.

PMID- 17006514
TI  - Centrosome polarization delivers secretory granules to the immunological synapse.
AB  - Cytotoxic T lymphocytes (CTLs) destroy virally infected and tumorigenic cells by
      releasing the contents of specialized secretory lysosomes--termed 'lytic
      granules'--at the immunological synapse formed between the CTL and the target. On
      contact with the target cell, the microtubule organizing centre of the CTL
      polarizes towards the target and granules move along microtubules in a minus-end
      direction towards the polarized microtubule organizing centre. However, the final
      steps of secretion have remained unclear. Here we show that CTLs do not require
      actin or plus-end microtubule motors for secretion, but instead the centrosome
      moves to and contacts the plasma membrane at the central supramolecular
      activation cluster of the immunological synapse. Actin and IQGAP1 are cleared
      away from the synapse, and granules are delivered directly to the plasma
      membrane. These data show that CTLs use a previously unreported mechanism for
      delivering secretory granules to the immunological synapse, with granule
      secretion controlled by centrosome delivery to the plasma membrane.

PMID- 17006515
TI  - Structural insights into yeast septin organization from polarized fluorescence
      microscopy.
AB  - Septins are polymerizing GTPases that function in cortical organization and cell
      division. In Saccharomyces cerevisiae they localize at the isthmus between the
      mother and the daughter cells, where they undergo a transition from a non-dynamic
      hourglass-shaped assembly to two separate rings, at the onset of cytokinesis.
      Septins form filaments as pure protein and in vivo, but the filament organization
      within the hourglass and ring structures is controversial. Here, we use polarized
      fluorescence microscopy of orientationally constrained green fluorescent protein
      to determine septin filament organization and dynamics in living yeast. We found
      that the hourglass is made of filaments aligned along the yeast bud neck. During
      the transition from hourglass to rings the filaments rotate through 90 degrees in
      the membrane plane and become circumferential. These data resolve a long-standing
      controversy in the field and provide strong evidence that septins have a
      mechanical function in cell division.

PMID- 17006516
TI  - Ion permeation through the Na+,K+-ATPase.
AB  - P-type ATPase pumps generate concentration gradients of cations across membranes
      in nearly all cells. They provide a polar transmembrane pathway, to which access
      is strictly controlled by coupled gates that are constrained to open alternately,
      thereby enabling thermodynamically uphill ion transport (for example, see ref.
      1). Here we examine the ion pathway through the Na+,K+-ATPase, a representative P
      type pump, after uncoupling its extra- and intracellular gates with the marine
      toxin palytoxin. We use small hydrophilic thiol-specific reagents as
      extracellular probes and we monitor their reactions, and the consequences, with
      cysteine residues introduced along the anticipated cation pathway through the
      pump. The distinct effects of differently charged reagents indicate that a wide
      outer vestibule penetrates deep into the Na+,K+-ATPase, where the pathway narrows
      and leads to a charge-selectivity filter. Acidic residues in this region, which
      are conserved to coordinate pumped ions, allow the approach of cations but
      exclude anions. Reversing the charge at just one of those positions converts the
      pathway from cation selective to anion selective. Close structural homology among
      the catalytic subunits of Ca2+-, Na+,K+- and H+,K+-ATPases argues that their
      extracytosolic cation exchange pathways all share these physical characteristics.

PMID- 17006524
TI  - Adjustable fortification of human milk fed to preterm infants.

PMID- 17006525
TI  - Bronchopulmonary dysplasia in very low birth weight infants is associated with
      prolonged hospital stay.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with prolonged
      hospital length of stay (LOS) and delayed discharge home. OBJECTIVES: To evaluate
      the association between BPD and LOS and to assess the contribution of concomitant
      major morbidities on LOS among infants with BPD. STUDY DESIGN: A population-based
      observational study of very low birth weight (VLBW) infants born from 1995
      through 2003. Multivariate analyses, adjusted for perinatal variables, assessed
      the association between BPD and concomitant morbidities on LOS. RESULTS: Of 10
      134 survivors, 1926 (19.0%) had BPD. The adjusted LOS for infants with and
      without BPD was 84.1 days (95% CI, 82.8, 85.6) and 58.1 days (95% CI, 57.2,
      59.0), respectively. Addition of a single concomitant morbidity increased mean
      LOS by 4 to 13 days. CONCLUSIONS: BPD is a major cause of increased length of
      hospitalization among VLBW infants. Preventive or therapeutic modalities are
      required to reduce the significant burden of this condition.

PMID- 17006526
TI  - Failed methotrexate termination of pregnancy: a case report.
AB  - We report a case of a fetus with shortened proximal long bones, ambiguous
      genitalia, intrauterine growth restriction and abnormal umbilical artery Doppler
      velocities observed on antenatal ultrasound exam. At 34 weeks the patient
      revealed methotrexate/misoprostol exposure at 6 weeks gestational age in
      attempted medical termination of pregnancy. On newborn exam, the baby had
      dysmorphic facial features, a short torso, scoliosis, a micropenis (phallus <1
      cm) and shortened proximal long bones both upper and lower extremities. X-ray
      exam revealed a hemivertebra at T10 level, rib abnormalities, shortened proximal
      long bones, an absent pubic bone and bilateral knee ossification centers. With
      methotrexate exposure, improved counseling and surveillance could potentially
      avoid these significant abnormalities and prevent psychological distress.

PMID- 17006527
TI  - Successful treatment with oral valganciclovir in immunocompetent infant with
      gastrointestinal manifestations of cytomegalovirus infection.
AB  - A 3-month-old male infant was admitted to hospital with anemia. Follow-up
      controls revealed the presence of specific cytomegalovirus (CMV) antibodies.
      Virus was isolated from urine, blood, and saliva. At 7 months of age, he
      presented with melena. Polymerase chain reaction (PCR) of biopsy samples from the
      duodenum was positive for CMV. Anemia resolved after starting antiviral therapy
      with oral valganciclovir.

PMID- 17006528
TI  - Cannula tip intravascular migration in an infant.
AB  - In infants, the tip of a cannula is sometimes used as introducer during
      peripherally inserted central catheters placement. We report a rare complication
      of this procedure, characterized by intravascular migration of the cannula tip
      during peripheral insertion of a central venous catheter. We review this unlikely
      complication and treatment options.

PMID- 17006529
TI  - A newborn with multiple fractures as first presentation of infantile
      myofibromatosis.
AB  - Pathological fractures occur in infancy from a variety of causes, but are a rare
      condition during neonatal period. We describe the case of a male newborn with a
      metaphyseal fracture of femur and multiple lytic lesions, diagnosed as infantile
      myofibromatosis.

PMID- 17006530
TI  - Inheritance of litter size at birth in farmed arctic foxes (Alopex lagopus,
      Canidae, Carnivora).
AB  - Natural populations of the arctic fox (Alopex lagopus, Canidae, Carnivora) differ
      drastically in their reproductive strategy. Coastal foxes, which depend on stable
      food resources, produce litters of moderate size. Inland foxes feed on small
      rodents, whose populations are characterized by cycling fluctuation. In the years
      with low food supply, inland fox populations have a very low rate of
      reproduction. In the years with high food supply, they undergo a population
      explosion. To gain insight into the genetic basis of the reproductive strategy of
      this species, we performed complex segregation analysis of the litter size in the
      extended pedigree of the farmed arctic foxes involving 20,665 interrelated
      animals. Complex segregation analysis was performed using a mixed model assuming
      that the trait was under control of a major gene and a large number of additive
      genetic and random factors. To check the significance of any major gene effect,
      we used Elston-Stewart transmission probability test. Our analysis demonstrated
      that the inheritance of this trait can be described within the frameworks of a
      major gene model with recessive control of low litter size. This model was also
      supported by the pattern of its familial segregation and by comparison of the
      distributions observed in the population and that expected under our model. We
      suggest that a system of balanced polymorphism for litter size in the farmed
      population might have been established in natural populations of arctic foxes as
      a result of adaptation to the drastic fluctuations in prey availability.

PMID- 17006531
TI  - Fine-scale population differentiation and gene flow in a terrestrial salamander
      (Plethodon cinereus) living in continuous habitat.
AB  - Several recent studies have shown that amphibian populations may exhibit high
      genetic subdivision in areas with recent fragmentation and urban development.
      Less is known about the potential for genetic differentiation in continuous
      habitats. We studied genetic differentiation of red-backed salamanders (Plethodon
      cinereus) across a 2-km transect through continuous forest in Virginia, USA. Mark
      recapture studies suggest very little dispersal for this species, whereas homing
      experiments and post-Pleistocene range expansion both suggest greater dispersal
      abilities. We used six microsatellite loci to examine genetic population
      structure and differentiation between eight subpopulations of red-backed
      salamanders at distances from 200 m to 2 km. We also used several methods to
      extrapolate dispersal frequencies and test for sex-biased dispersal. We found
      small, but detectable differentiation among populations, even at distances as
      small as 200 m. Differentiation was closely correlated with distance and both
      Mantel tests and assignment tests were consistent with an isolation-by-distance
      model for the population. Extrapolations of intergenerational variance in spatial
      position (sigma(2)<15 m(2)) and pair-wise dispersal frequencies (4 Nm < 25 for
      plots separated by 300 m) both suggest limited gene flow. Additionally, tests for
      sex-biased dispersal imply that dispersal frequency is similarly low for both
      sexes. We suggest that these low levels of gene flow and the infrequent dispersal
      observed in mark-recapture studies may be reconciled with homing ability and
      range expansion if dispersing animals rarely succeed in breeding in saturated
      habitats, if dispersal is flexible depending on the availability of habitat, or
      if dispersal frequency varies across the geographic range of red-backed
      salamanders.

PMID- 17006532
TI  - Quantitative and evolutionary biology of alternative splicing: how changing the
      mix of alternative transcripts affects phenotypic plasticity and reaction norms.
AB  - Alternative splicing (AS) of pre-messenger RNA is a common phenomenon that
      creates different transcripts from a single gene, and these alternative
      transcripts affect phenotypes. The majority of AS research has examined tissue
      and developmental specificity of expression of particular AS transcripts, how
      this specificity affects cell function, and how aberrant AS is related to
      disease. Few studies have examined quantitative between-individual variation in
      AS within a cell or tissue type, or in relation to phenotypes, but the results
      are compelling: quantitative variation in AS affects plastic traits such as
      stress, anxiety, fear, egg production, muscle performance, energetics and plant
      growth. Genomic analyses of AS are also at a nascent stage, but have revealed a
      number of significant evolutionary patterns. Growing knowledge of upstream genes
      and kinases that regulate AS provides the as-yet little explored potential to
      examine how these genes and pathways respond to environmental and genotype
      variables. Research in this area can provide glimpses of a labyrinth of genetic
      architectures that have rarely been considered in evolutionary and organismal
      biology, or in quantitative genetics. The scarcity of contribution to knowledge
      about AS from these fields is illustrated by the fact that heritability of
      quantitative variation in AS has not yet been determined for any gene in any
      organism. New research tactics that incorporate quantitative analyses of AS will
      allow organismal and evolutionary biologists to attain a fuller mechanistic
      understanding of many of the traits they study, and may lead to more rapid
      discovery of functionally important polymorphisms.

PMID- 17006533
TI  - The recent demographic and adaptive history of Drosophila melanogaster.
AB  - Population genetic analyses of the past two decades confirmed an earlier
      hypothesis by L Tsacas and D Lachaise that the cosmopolitan species Drosophila
      melanogaster has an Afrotropical origin, and that it colonized the rest of the
      world only very recently. Maximum likelihood analyses based on multilocus data
      suggest that the putative ancestral African population expanded its size about
      60,000 years ago (ya). These demographic changes were accompanied by the fixation
      of numerous beneficial mutations, as revealed by signatures of positive
      directional selection in the genome (selective sweeps). The estimated rate of
      adaptive substitution on the X chromosome is in the order of 10(-11) per
      nucleotide site per generation. Comparable (but not significantly higher)
      substitution rates are found in derived populations that colonized new habitats
      outside Africa, such as in a European population that branched off from the
      African lineage about 16,000 ya.

PMID- 17006534
TI  - Self-fertilization in mosses: a comparison of heterozygote deficiency between
      species with combined versus separate sexes.
AB  - Self-fertilization is a key difference of adaptive significance between species
      with combined versus separate sexes. In haploid-dominant species such as mosses
      and ferns, species with either combined or separate sexes (monoicous and
      dioicous, respectively) have the potential to self-fertilize (intergametophytic
      selfing), but being monoicous allows an additional mode of selfing
      (intragametophytic selfing). We used allozyme electrophoresis to estimate
      deviations from expected levels of heterozygosity under Hardy-Weinberg
      equilibrium to infer selfing rates in 10 moss species from 36 New Zealand
      populations. We found that while there were deficiencies of heterozygotes
      compared to expectation in both monoicous and dioicous mosses, monoicous species
      had significantly higher levels of heterozygote deficiency than dioicous species
      (F(IS)=0.89+/-0.12 and 0.41+/-0.11, respectively). Estimated selfing rates
      suggest that selfing occurs frequently in monoicous populations, and rarely in
      dioicous populations. However, in two dioicous species (Polytrichadelphus
      magellanicus and Breutelia pendula), we found significant indications of mixed
      mating or biparental inbreeding in a handful of populations. These data provide
      the first analysis of heterozygote deficiency and selfing among haploid-dominant
      species with breeding system variation, and we discuss our results with respect
      to the consequences of inbreeding depression and the evolution of breeding
      systems.

PMID- 17006535
TI  - Polluting gene flow from crops: radishes gone wild.

PMID- 17006536
TI  - The longevity of Y chromosomes: the human Y chromosome is not dead (yet).

PMID- 17006537
TI  - A ubiquitin ligase complex assembles linear polyubiquitin chains.
AB  - The ubiquitin system plays important roles in the regulation of numerous cellular
      processes by conjugating ubiquitin to target proteins. In most cases, conjugation
      of polyubiquitin to target proteins regulates their function. In the
      polyubiquitin chains reported to date, ubiquitin monomers are linked via
      isopeptide bonds between an internal Lys and a C-terminal Gly. Here, we report
      that a protein complex consisting of two RING finger proteins, HOIL-1L and HOIP,
      exhibits ubiquitin polymerization activity by recognizing ubiquitin moieties of
      proteins. The polyubiquitin chain generated by the complex is not formed by Lys
      linkages, but by linkages between the C- and N-termini of ubiquitin, indicating
      that the ligase complex possesses a unique feature to assemble a novel head-to
      tail linear polyubiquitin chain. Moreover, the complex regulates the stability of
      Ub-GFP (a GFP fusion protein with an N-terminal ubiquitin). The linear
      polyubiquitin chain generated post-translationally may function as a new
      modulator of proteins.

PMID- 17006538
TI  - Restraining the conformation of HIV-1 gp120 by removing a flexible loop.
AB  - The trimeric HIV/SIV envelope glycoprotein, gp160, is cleaved to noncovalently
      associated fragments, gp120 and gp41. Binding of gp120 to viral receptors leads
      to large structural rearrangements in both fragments. The unliganded gp120 core
      has a disordered beta3-beta5 loop, which reconfigures upon CD4 binding into an
      ordered, extended strand. Molecular modeling suggests that residues in this loop
      may contact gp41. We show here that deletions in the beta3-beta5 loop of HIV-1
      gp120 weaken the binding of CD4 and prevent formation of the epitope for
      monoclonal antibody (mAb) 17b (which recognizes the coreceptor site). Formation
      of an encounter complex with CD4 binding and interactions of gp120 with mAbs b12
      and 2G12 are not affected by these deletions. Thus, deleting the beta3-beta5 loop
      blocks the gp120 conformational change and may offer a strategy for design of
      restrained immunogens. Moreover, mutations in the SIV beta3-beta5 loop lead to
      greater spontaneous dissociation of gp120 from cell-associated trimers. We
      suggest that the CD4-induced rearrangement of this loop releases structural
      constraints on gp41 and thus potentiates its fusion activity.

PMID- 17006540
TI  - Unliganded thyroid hormone receptor is essential for Xenopus laevis eye
      development.
AB  - Thyroid hormone receptors generally activate transcription of target genes in the
      presence of thyroid hormone (T(3)) and repress their transcription in its
      absence. Here, we investigated the role of unliganded thyroid hormone receptor
      (TR) during vertebrate development using an amphibian model. Previous studies led
      to the hypothesis that before production of endogenous T(3), the presence of
      unliganded receptor is essential for premetamorphic tadpole growth. To test this
      hypothesis, we generated a Xenopus laevis TR beta mutant construct ineffective
      for gene repression owing to impaired corepressor NCoR recruitment.
      Overexpression by germinal transgenesis of the mutant receptor leads to lethality
      during early development with numerous defects in cranio-facial and eye
      development. These effects correlate with TR expression profiles at these early
      stages. Molecular analysis of transgenic mutants reveals perturbed expression of
      genes involved in eye development. Finally, treatment with iopanoic acid or NH-3,
      modulators of thyroid hormone action, leads to abnormal eye development. In
      conclusion, the data reveal a role of unliganded TR in eye development.

PMID- 17006539
TI  - Tissue kallikrein stimulates Ca(2+) reabsorption via PKC-dependent plasma
      membrane accumulation of TRPV5.
AB  - The transient receptor potential vanilloid 5 (TRPV5) channel determines urinary
      Ca(2+) excretion, and is therefore critical for Ca(2+) homeostasis.
      Interestingly, mice lacking the serine protease tissue kallikrein (TK) exhibit
      robust hypercalciuria comparable to the Ca(2+) leak in TRPV5 knockout mice. Here,
      we delineated the molecular mechanism through which TK stimulates Ca(2+)
      reabsorption. Using TRPV5-expressing primary cultures of renal Ca(2+)
      transporting epithelial cells, we showed that TK activates Ca(2+) reabsorption.
      The stimulatory effect of TK was mimicked by bradykinin (BK) and could be
      reversed by application of JE049, a BK receptor type 2 antagonist. A cell
      permeable analog of DAG increased TRPV5 activity within 30 min via protein kinase
      C activation of the channel since mutation of TRPV5 at the putative PKC
      phosphorylation sites S299 and S654 prevented the stimulatory effect of TK. Cell
      surface labeling revealed that TK enhances the amount of wild-type TRPV5
      channels, but not of the TRPV5 S299A and S654A mutants, at the plasma membrane by
      delaying its retrieval. In conclusion, TK stimulates Ca(2+) reabsorption via the
      BK-activated PLC/DAG/PKC pathway and the subsequent stabilization of the TRPV5
      channel at the plasma membrane.

PMID- 17006541
TI  - Regulation of TopBP1 oligomerization by Akt/PKB for cell survival.
AB  - Regulation of E2F1-mediated apoptosis is essential for proper cellular growth.
      This control requires TopBP1, a BRCT (BRCA1 carboxyl-terminal) domain-containing
      protein, which interacts with E2F1 but not other E2Fs and represses its
      proapoptotic activity. We now show that the regulation of E2F1 by TopBP1 involves
      the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway, and is independent of
      pocket proteins. Akt phosphorylates TopBP1 in vitro and in vivo. Phosphorylation
      by Akt induces oligomerization of TopBP1 through its seventh and eighth BRCT
      domains. The Akt-dependent oligomerization is crucial for TopBP1 to interact with
      and repress E2F1. Akt phosphorylation is also required for interaction between
      TopBP1 and Miz1 or HPV16 E2, and repression of Miz1 transcriptional activity,
      suggesting a general role for TopBP1 oligomerization in the control of
      transcription factors. Together, this study defines a novel pathway involving
      PI3K-Akt-TopBP1 for specific control of E2F1 apoptosis, in parallel with cyclin
      Cdk-Rb for general control of E2F activities.

PMID- 17006542
TI  - A molecular insight of Hes5-dependent inhibition of myelin gene expression: old
      partners and new players.
AB  - This study identifies novel mechanisms of Hes5 function in developmental
      myelination. We report here upregulation of myelin gene expression in Hes5-/-
      mice compared to wild-type siblings and downregulation in overexpressing
      progenitors. This effect was only partially explained by the ability to regulate
      the levels of Mash1 and bind to N boxes in myelin promoters, as deletion of the
      DNA-binding domain of Hes5 did not suppress its inhibitory role on myelin gene
      expression. Novel mechanisms of Hes5 function in the oligodendrocyte lineage
      include the regulation of feedback loops with the cell-specific transcriptional
      activator Sox10. In progenitors with low levels of Sox10, Hes5 further decreases
      the bioavailability of this protein by transcriptional inhibition and direct
      sequestration of this activator. Increasing levels of Sox10 in progenitors, in
      turn, bind to Hes5 and titrate out its inhibitory effect by sequestration and
      displacement of the repressive complexes from myelin promoters. Thus, Hes5
      dependent modulation of myelin gene expression involves old players (i.e. Mash1)
      and novel mechanisms of transcriptional regulation that include cell-specific
      regulatory loops with transcriptional activators (i.e. Sox10).

PMID- 17006543
TI  - Mdm2 is involved in the ubiquitination and degradation of G-protein-coupled
      receptor kinase 2.
AB  - G-protein-coupled receptor kinase 2 (GRK2) is a central regulator of G-protein
      coupled receptor signaling. We report that Mdm2, an E3-ubiquitin ligase involved
      in the control of cell growth and apoptosis, plays a key role in GRK2
      degradation. Mdm2 and GRK2 association is enhanced by beta(2)-adrenergic receptor
      stimulation and beta-arrestin. Increased Mdm2 expression accelerates GRK2
      proteolysis and promotes kinase ubiquitination at defined residues, whereas GRK2
      turnover is markedly impaired in Mdm2-deficient cells. Moreover, we find that
      activation of the PI3K/Akt pathway by insulin-like growth factor-1 alters Mdm2
      mediated GRK2 degradation, leading to enhanced GRK2 stability and increased
      kinase levels. These data put forward a novel mechanism for controlling GRK2
      expression in physiological and pathological conditions.

PMID- 17006544
TI  - Retrotranslocation of a viral A/B toxin from the yeast endoplasmic reticulum is
      independent of ubiquitination and ERAD.
AB  - K28 is a viral A/B toxin that traverses eukaryotic cells by endocytosis and
      retrograde transport through the secretory pathway. Here we show that toxin
      retrotranslocation from the endoplasmic reticulum (ER) requires Kar2p/BiP, Pdi1p,
      Scj1p, Jem1p, and proper maintenance of Ca(2+) homeostasis. Neither cytosolic
      chaperones nor Cdc48p/Ufd1p/Npl4p complex components or proteasome activity are
      required for ER exit, indicating that K28 retrotranslocation is mechanistically
      different from classical ER-associated protein degradation (ERAD). We demonstrate
      that K28 exits the ER in a heterodimeric but unfolded conformation and
      dissociates into its subunits as it emerges into the cytosol where beta is
      ubiquitinated and degraded. ER export and in vivo toxicity were not affected in a
      lysine-free K28 variant nor under conditions when ubiquitination and proteasome
      activity was blocked. In contrast, toxin uptake from the plasma membrane required
      Ubc4p (E2) and Rsp5p (E3) and intoxicated ubc4 and rsp5 mutants accumulate K28 at
      the cell surface incapable of toxin internalization. We propose a model in which
      ubiquitination is involved in the endocytic pathway of the toxin, while ER-to
      cytosol retrotranslocation is independent of ubiquitination, ERAD and proteasome
      activity.

PMID- 17006546
TI  - p21((WAF1))-mediated transcriptional targeting of inducible nitric oxide synthase
      gene therapy sensitizes tumours to fractionated radiotherapy.
AB  - Cancer gene therapy that utilizes toxic transgene products requires strict
      transcriptional targeting to prevent adverse normal tissue effects. We report on
      the use of a promoter derived from the cyclin dependent kinase inhibitor,
      p21((WAF1)), to control transgene expression. We demonstrate that this promoter
      is relatively silent in normal cells (L132, FSK, HMEC-1) compared to the almost
      constitutive expression obtained in tumour cells (DU145, LNCaP, HT29 and MCF-7)
      of varying p53 status, a characteristic that will be important in gene therapy
      protocols. In addition, we found that the p21((WAF1)) promoter could be further
      induced by both external beam radiation (up to eight-fold in DU145 cells),
      intracellular-concentrated radionuclides ([(211)At]MABG) (up to 3.5-fold in SK-N
      BE(2c) cells) and hypoxia (up to four-fold in DU145 cells). We have previously
      achieved significant radiosensitization of tumour cells both in vitro and in vivo
      by using inducible nitric oxide synthase (iNOS) gene therapy to generate the
      potent radiosensitizer, nitric oxide (NO(.-)). Here, we report that a clinically
      relevant schedule of p21((WAF1))-driven iNOS gene therapy significantly
      sensitized both p53 wild-type RIF-1 tumours and p53 mutant HT29 tumours to
      fractionated radiotherapy. Our data highlight the utility of this
      p21((WAF1))/iNOS-targeted approach.

PMID- 17006545
TI  - Role of conserved intracellular motifs in Serrate signalling, cis-inhibition and
      endocytosis.
AB  - Notch is the receptor in a signalling pathway that operates in a diverse spectrum
      of developmental processes. Its ligands (e.g. Serrate) are transmembrane proteins
      whose signalling competence is regulated by the endocytosis-promoting E3
      ubiquitin ligases, Mindbomb1 and Neuralized. The ligands also inhibit Notch
      present in the same cell (cis-inhibition). Here, we identify two conserved motifs
      in the intracellular domain of Serrate that are required for efficient
      endocytosis. The first, a dileucine motif, is dispensable for trans-activation
      and cis-inhibition despite the endocytic defect, demonstrating that signalling
      can be separated from bulk endocytosis. The second, a novel motif, is necessary
      for interactions with Mindbomb1/Neuralized and is strictly required for Serrate
      to trans-activate and internalise efficiently but not for it to inhibit Notch
      signalling. Cis-inhibition is compromised when an ER retention signal is added to
      Serrate, or when the levels of Neuralized are increased, and together these data
      indicate that cis-inhibitory interactions occur at the cell surface. The balance
      of ubiquitinated/unubiquitinated ligand will thus affect the signalling capacity
      of the cell at several levels.

PMID- 17006548
TI  - Characterization of capsid-modified adenovirus vectors containing heterologous
      peptides in the fiber knob, protein IX, or hexon.
AB  - Adenovirus (Ad) vectors are widely used in gene therapy and in vitro/in vivo gene
      transfer because of their high transduction efficiency. However, Ad vector
      application in the gene therapy field is limited by poor transduction into cells
      not expressing the primary receptor, coxsackievirus and adenovirus receptor. To
      overcome this problem, several types of capsid-modified Ad vectors have been
      developed. The HI loop or C-terminus of the fiber knob, the C-terminus of the
      protein IX (pIX) and the hypervariable region 5 of the hexon are promising
      candidate locations for displaying foreign peptide sequences. In the present
      study, we constructed Ad vectors in which each of the above region was modified
      by a simple in vitro ligation-based method, and examined the characterization of
      each Ad vector containing the FLAG tag (DYKDDDDK) or RGD (CDCRGDCFC) peptide.
      Enzyme-linked immunosorbent assay examining the surface expression of foreign
      peptides on the virus suggested that foreign peptides are exposed on virion
      surfaces in all types vectors and that the hexon was the most efficiently
      reacted, reflecting the copy number of the modification. However, in the case of
      the transduction efficiency of Ad vectors containing the RGD peptides, the
      modification of pIX and the hexon showed no effect. The modification of the HI
      loop of the fiber knob was the most efficient, followed by the modification of
      the C-terminus region of the fiber knob. These comparative analyses, together
      with a simple construction method for each modified Ad vector, could provide
      basic information for the generation of capsid-modified Ad vectors.

PMID- 17006547
TI  - Glucose-6-phosphate transporter gene therapy corrects metabolic and myeloid
      abnormalities in glycogen storage disease type Ib mice.
AB  - Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the
      glucose-6-phosphate transporter (G6PT), an endoplasmic reticulum-associated
      transmembrane protein that is ubiquitously expressed. GSD-Ib patients suffer from
      disturbed glucose homeostasis and myeloid dysfunctions. To evaluate the
      feasibility of gene replacement therapy for GSD-Ib, we have infused adenoviral
      (Ad) vector containing human G6PT (Ad-hG6PT) into G6PT-deficient (G6PT(-/-)) mice
      that manifest symptoms characteristics of the human disorder. Ad-hG6PT infusion
      restores significant levels of G6PT mRNA expression in the liver, bone marrow and
      spleen, and corrects metabolic as well as myeloid abnormalities in G6PT(-/-)
      mice. The G6PT(-/-) mice receiving gene therapy exhibit improved growth;
      normalized serum profiles for glucose, cholesterol, triglyceride, uric acid and
      lactic acid; and reduced hepatic glycogen deposition. The therapy also corrects
      neutropenia and lowers the elevated serum levels of granulocyte colony
      stimulating factor. The development of bone and spleen in the infused G6PT(-/-)
      mice is improved and accompanied by increased cellularity and normalized myeloid
      progenitor cell frequencies in both tissues. This effective use of gene therapy
      to correct metabolic imbalances and myeloid dysfunctions in GSD-Ib mice holds
      promise for the future of gene therapy in humans.

PMID- 17006549
TI  - Proposal of a service delivery integration index of home care for older persons:
      application in several European cities.
AB  - PURPOSE: To propose an integration index of home care delivery to older persons,
      to study its validity and to apply it to home care services of European cities.
      THEORY: Home care delivery integration was based on two dimensions referring to
      process-centred integration and organisational structure approach. METHOD: Items
      considered as part of both dimensions according to an expert consensus (face
      validity) were extracted from a standardised questionnaire used in "Aged in Home
      care" (AdHoc) study to capture basic characteristics of home care services. Their
      summation leads to a services' delivery integration index. This index was applied
      to AdHoc services. A factor analysis was computed in order to empirically test
      the validity of the theoretical constructs. The plot of the settings was
      performed. RESULTS: Application of the index ranks home care services in four
      groups according to their score. Factor analysis identifies a first factor which
      opposes working arrangement within service to organisational structure bringing
      together provisions for social care. A second factor corresponds to basic nursing
      care and therapies. Internal consistency for those three domains ranges from 0.78
      to 0.93. When plotting the different settings different models of service
      delivery appear. CONCLUSION: The proposed index shows that behind a total score
      several models of care delivery are hidden. Comparison of service delivery
      integration should take into account this heterogeneity.

PMID- 17006550
TI  - Policy change and policy dilemmas: interpreting the community services White
      Paper in England.
AB  - CONTEXT: In 2006 the Labour Government in England published its long awaited
      White Paper on 'community services', following on from the 2005 Green Paper on
      the future of social care. The policy envisages an unprecedented shift of
      activity and resources from acute care to community settings, along with a much
      stronger focus on preventive care. Several mechanisms are to be put in place to
      ensure this shift takes place, most notably practice-based commissioning,
      payments-by-results and enhanced partnership working. PURPOSE: This article
      outlines the intended changes and assesses the extent to which they add up to a
      coherent strategy. CONCLUSION: It is argued that although there is widespread
      support for the overall vision, the strategy contains some difficult policy
      tensions that are common to other welfare systems. These will have to be
      addressed if the vision is to be a reality.

PMID- 17006551
TI  - Disease management programs in the USA and Europe are comparable (yet?)
      different.

PMID- 17006552
TI  - Integrated care: a fresh perspective for international health policies in low and
      middle-income countries.
AB  - PURPOSE: To propose a social-and-democrat health policy alternative to the
      current neoliberal one. CONTEXT OF CASE: The general failure of neoliberal health
      policies in low and middle-income countries justifies the design of an
      alternative to bring disease control and health care back in step with ethical
      principles and desired outcomes. DATA SOURCES: National policies, international
      programmes and pilot experiments--including those led by the authors--are
      examined in both scientific and grey literature. CASE DESCRIPTION: We call for
      the promotion of a publicly-oriented health sector as a cornerstone of such
      alternative policy. We define 'publicly-oriented' as opposed to 'private-for
      profit' in terms of objectives and commitment, not of ownership. We classify
      development strategies for such a sector according to an organisation-based
      typology of health systems defined by Mintzberg. As such, strategies are adapted
      to three types of health systems: machine bureaucracies, professional
      bureaucracies and divisionalized forms. We describe avenues for family and
      community health and for hospital care. We stress social control at the
      peripheral level to increase accountability and responsiveness. Community-based,
      national and international sources are required to provide viable financing.
      CONCLUSIONS AND DISCUSSION: Our proposed social-and-democrat health policy calls
      for networking, lobbying and training as a joint effort in which committed health
      professionals can lead the way.

PMID- 17006553
TI  - Disintegrated care: the Achilles heel of international health policies in low and
      middle-income countries.
AB  - PURPOSE: To review the evidence basis of international aid and health policy.
      CONTEXT OF CASE: Current international aid policy is largely neoliberal in its
      promotion of commoditization and privatisation. We review this policy's
      responsibility for the lack of effectiveness in disease control and poor access
      to care in low and middle-income countries. DATA SOURCES: National policies,
      international programmes and pilot experiments are examined in both scientific
      and grey literature. CONCLUSIONS AND DISCUSSION: We document how health care
      privatisation has led to the pool of patients being cut off from public disease
      control interventions--causing health care disintegration--which in turn resulted
      in substandard performance of disease control. Privatisation of health care also
      resulted in poor access. Our analysis consists of three steps. Pilot local
      contracting-out experiments are scrutinized; national health care records of
      Colombia and Chile, two countries having adopted contracting-out as a basis for
      health care delivery, are critically examined against Costa Rica; and specific
      failure mechanisms of the policy in low and middle-income countries are explored.
      We conclude by arguing that the negative impact of neoliberal health policy on
      disease control and health care in low and middle-income countries justifies an
      alternative aid policy to improve both disease control and health care.

PMID- 17006554
TI  - Biventricular pacing in congestive heart failure.

PMID- 17006555
TI  - Current status of internal cardioversion in atrial fibrillation.

PMID- 17006556
TI  - Radiofrequency catheter ablation of supraventricular tachycardia.

PMID- 17006557
TI  - High resolution electrocardiography.
AB  - Over the past decade, significant advances were made in the research, diagnosis,
      and treatment of cardiovascular diseases. Such progress was in every sphere of
      cardiology that includes non-invasive, minimally invasive, and invasive
      technologies. Interpretive electrocardiography, cardiac pacemakers, cardiac
      stents, and angioplasty are some areas where the progress has been significant.
      Non-invasive methods of diagnosis of cardiac disorders involve digital recording
      of cardiac signals at the body surface (chest) and subsequent computerized
      analysis. Such methods and instruments provide a vital first step to the
      diagnosis of the heart without involving surgical procedures. One such non
      invasive field is High Resolution Electrocardiography (HRECG). A high-resolution
      electrocardiogram detects very low amplitude signals in the ventricles called
      'Late Potentials' in patients with abnormal heart conditions. A standard
      electrocardiogram cannot detect these signals. The presence of late potentials is
      widely accepted to have prognostic significance in patients after Acute
      Myocardial Infarction (AMI) High Resolution Electrocardiography enhances the
      diagnostic capabilities of ECGs. This article describes the principles involved
      in HRECG and the techniques that are employed to derive such superior diagnostic
      capabilities. The use of these techniques may lead to more discoveries in the
      causes of cardiac disorders and improved drug discoveries to combat such
      conditions.

PMID- 17006558
TI  - Development of pacing, electrophysiology and defibrillation in India.

PMID- 17006559
TI  - Reminiscences of the first His bundle electrography in India.

PMID- 17006560
TI  - Electromagnetic interference in implantable rhythm devices--the Indian scenario.

PMID- 17006561
TI  - Temperature controlled radiofrequency ablation.

PMID- 17006563
TI  - Electromagnetic interference in patients with implanted cardioverter
      defibrillators and implantable loop recorders.

PMID- 17006562
TI  - Electromagnetic interference on pacemakers.
AB  - External sources, either within or outside the hospital environment, may
      interfere with the appropriate function of pacemakers which are being implanted
      all around the world in current medical practice. The patient and the physician
      who is responsible for follow-up of the pacing systems may be confronted with
      some specific problems regarding the various types of electromagnetic
      interference (EMI). To avoid these unwanted EMI effects one must be aware of this
      potential problem and need to take some precautions. The effects of EMI on
      pacemaker function and precautions to overcome some specific problems were
      discussed in this review article. There are many sources of EMI interacting with
      pacemakers. Magnetic resonance imaging creates real problem and should be avoided
      in pacemaker patients. Cellular phones might be responsible for EMI when they
      were held on the same side with the pacemaker. Otherwise they don't cause any
      specific type of interaction with pacemakers. Sale security systems are not a
      problem if one walks through it without lingering in or near it. Patients having
      unipolar pacemaker systems are prone to develop EMI because of pectoral muscle
      artifacts during vigorous active physical exercise.

PMID- 17006564
TI  - Ablation of atrial flutter: block (isthmus conduction) or not a block, that is
      the question?
AB  - It is important to identify residual slow conduction and minimize the chance of
      resumption of conduction after right atrial isthmus ablation to reduce the chance
      of recurrence of atrial flutter (AFL). The aim of this article is to discuss the
      best possible way of confirming a bi-directional isthmus conduction (BIC) block
      after ablation of an isthmus-dependent AFL. A combination of activation and
      double potential mapping seems to be the most practical way of acutely confirming
      the BIC block.

PMID- 17006566
TI  - Brugada syndrome: the syndrome of right bundle branch block, ST segment elevation
      in V1 to V3 and sudden death.

PMID- 17006565
TI  - Managing ventricular tachyarrhythmias in the developing world: insights from
      recent ICD trials.

PMID- 17006567
TI  - Evaluation of syncope: an overview.

PMID- 17006568
TI  - A re-analysis of our current understanding of isthmus-dependent atrial flutter:
      some gaps, some hypotheses.
AB  - The macro-reentrant circuit of isthmus-dependent atrial flutter (AFL) is located
      in the right atrium around the tricuspid annulus. High acute success and low
      recurrence rate makes isthmus ablation a definitive therapy for patients with
      only AFL. However, a review of the literature suggests that, different aspects of
      this macro-reentrant circuit are still not entirely understood, while new
      information continues to emerge. The aim of this article is to discuss some gaps
      in our "complete" understanding of isthmus-dependent AFL. Few hypotheses have
      been stated which are open to investigation.

PMID- 17006569
TI  - Management of the patient with an acute massive rise in the capture threshold.

PMID- 17006570
TI  - Arrhythmia care in India--poised for the big leap.

PMID- 17006571
TI  - Early history of cardiac pacing and defibrillation.

PMID- 17006572
TI  - Non-pharmacological treatment of atrial fibrillation.
AB  - In selected patients with atrial fibrillation and severe symptoms, non
      pharmacological treatment may be an alternative or supplement to drug therapy.
      Atrioventricular nodal radiofrequency ablation (requires pacemaker implantation),
      or atrial pacing for sick sinus syndrome, are established treatment modalities.
      All other non-pharmacological therapies for atrial fibrillation are still
      experimental. After the Maze operation, atrial depolarization has to follow one
      specific path determined by surgical scars in the myocardium. This prevents new
      episodes of atrial fibrillation, but at a cost of perioperative morbidity and
      mortality. Catheter-based "Maze-like" radiofrequency ablation is technically
      difficult, and thrombo-embolic complications may occur. Paroxysmal atrial
      fibrillation sometimes is initiated by spontaneous depolarizations in a pulmonary
      vein inlet. Radio frequency ablation against such focal activity has been
      reported with high therapeutic success, but the results await confirmation from
      several centres. For ventricular rate control, most electrophysiologists
      presently prefer ablation to induce a complete atrioventricular conduction block
      (with pacemaker) rather than trying to modify conduction by incomplete block.
      Atrial or dual chamber pacing may prevent atrial fibrillation induced by
      bradycardia. It remains to confirm that biatrial or multisite right atrial pacing
      prevents atrial fibrillation more efficiently than ordinary right atrial pacing.
      An atrial defibrillator is able to diagnose and convert atrial fibrillation. The
      equipment is expensive, and therapy without sedation may be unpleasant beyond
      tolerability.

PMID- 17006573
TI  - The implantable loop recorder: a tool that is "here to stay".

PMID- 17006574
TI  - Cardiac mapping: utility or futility?

PMID- 17006575
TI  - Arrhythmia diagnosis following an ICD shock: comment.

PMID- 17006577
TI  - Environmental planning and urban health.

PMID- 17006578
TI  - Infected pancreatic necrosis--an evaluation of the timing and technique of
      necrosectomy in a Southeast Asian population.
AB  - INTRODUCTION: Acute pancreatitis appears to be less prevalent in multi-ethnic
      Southeast Asia, where the aetiology also appears to be influenced by ethnicity.
      As with acute pancreatitis elsewhere, however, pancreatic necrosis is a cause of
      significant mortality and the aim of this study was to review our institutional
      experience with pancreatic necrosectomy. MATERIALS AND METHODS: The records of
      all patients who underwent pancreatic necrosectomy from January 2000 to December
      2004 were analysed. Indications for surgery were the presence of infected
      necrosis, unresolving sepsis attributable to ongoing pancreatitis or the presence
      of gas in the pancreatic bed on imaging. Surgical debridement was achieved by
      debridement with closure over drains or by debridement with open packing.
      RESULTS: The cohort comprised 14 of 373 patients admitted for acute pancreatitis
      (3.8%), with an overall mortality rate of 29%. All patients had infected necrosis
      with positive bacteriological cultures. Eight patients (57%) underwent
      debridement with closure over drains and 6 patients (43%) underwent debridement
      with open packing. All mortalities occurred in patients who underwent open
      packing, who were also associated with a higher mean Acute Physiology and Chronic
      Health Evaluation (APACHE) II score. The mortality rate in patients who underwent
      debridement less than 4 weeks after admission was 33% (2 of 6), compared with 25%
      (2 of 8) in patients who underwent debridement after 4 weeks. There were no
      mortalities in patients operated on after 6 weeks. CONCLUSION: Surgical
      debridement with closure of drains and a policy of performing delayed
      necrosectomy are viable in our population.

PMID- 17006579
TI  - Diabetic retinopathy in type II diabetics detected by targeted screening versus
      newly diagnosed in general practice.
AB  - INTRODUCTION: The aim of this study was to compare the occurrence of diabetic
      retinopathy in targeted screening diabetic patients (Group I) with newly
      diagnosed diabetic patients in general practice (Group II). MATERIALS AND
      METHODS: This was an observational cross-sectional study. Data were obtained from
      25,313 subjects who participated in the diabetic screening camps, and 128 newly
      diagnosed diabetes who presented to the diabetic retinopathy screening camps in
      general practice in rural and urban south India. The study variables were
      collected from all patients who underwent eye examination from the target
      screening detected diabetics [(n = 173) Group I] and those newly diagnosed in
      general practice [(n = 128) Group II]. The variations in prevalence of diabetic
      retinopathy and sight-threatening diabetic retinopathy in Group I and Group II
      and the factors affecting it were identified. RESULTS: The occurrence of diabetic
      retinopathy was 6.35% (95% CI, 2.5-9.5) in Group I and 11.71% (95% CI, 5.6-16.4)
      in Group II. No significant difference was observed on occurrence of diabetic
      retinopathy, including sightthreatening retinopathy, in rural versus urban
      population and in Group I versus Group II. Patients diagnosed in general practice
      (Group II) with systolic blood pressure (BP) >140 were more likely to have
      retinopathy (P = 0.02). CONCLUSIONS: Diabetic retinopathy including
      sightthreatening complications was found at the time of diagnosis of diabetes in
      the targeted screening group as well as in newly diagnosed diabetics in the
      general practice group.

PMID- 17006580
TI  - Role of ultrasound biomicroscopy (UBM) in the detection and localisation of
      anterior segment foreign bodies.
AB  - INTRODUCTION: The aim of this study was to investigate the role of ultrasound
      biomicroscopy (UBM) in imaging anterior segment foreign bodies and compare it
      with conventional B-scan ultrasound and computed tomography (CT). MATERIALS AND
      METHODS: The charts of 18 eyes with anterior segment foreign bodies were
      reviewed. The rates of detection of foreign bodies using ultrasound, CT scan and
      UBM were compared. RESULTS: The foreign body detection rates were 36.5% by
      ultrasound, 88.9% by CT scan, and 94.4% by UBM. The diagnosis of presence of a
      foreign body using UBM was made based on high reflective echoes causing shadowing
      or reverberations. In 7 eyes, UBM detected injury to the zonules, guiding the
      operative procedure. In the 8 eyes for which all tests were performed, rates of
      detection of foreign bodies were 25% (2/8) with ultrasound, 87.5% (7/8) with CT,
      and 100% (8/8) with UBM. CONCLUSION: UBM is a valuable adjunct for the accurate
      localisation of small foreign bodies, including cilia. It offers a higher
      detection rate than that provided by ultrasound and CT scan.

PMID- 17006581
TI  - Efficacy of measuring visual performance of LASIK patients under photopic and
      mesopic conditions.
AB  - INTRODUCTION: The aim of the study was to compare the visual performance of LASIK
      eyes measured using high-contrast logMAR letter charts under bright (photopic)
      and dim (mesopic) conditions. MATERIALS AND METHODS: A total of 46 subjects (35
      +/- 8 years of age) undergoing LASIK procedures were recruited for the study. The
      best spectacle-corrected visual acuity (BSCVA) of each subject was measured using
      the high-contrast ETDRS logMAR chart under photopic and mesopic conditions at 3
      visits: preoperative (Pre), 1 month postoperative (Post1) and 3 months
      postoperative (Post3). The differences in logMAR scores for the right eyes only
      were analysed for the Pre-Post1 (n = 46), Pre-Post3 (n = 18) and Post1-Post3 (n =
      16) comparisons. RESULTS: The logMAR scores of subjects were worse at the 1-month
      postoperative visit than preoperatively, and improvement in visual performance
      was seen at the 3-month postoperative visit. These changes in visual performance
      became more evident under mesopic conditions. The means and standard errors of
      the differences in logMAR scores for the Pre-Post3 (0.097 +/- 0.020) were
      slightly larger than those of the Pre-Post1 (-0.067 +/- 0.019) and Post1-Post3
      (0.031 +/- 0.012) comparisons. Under mesopic conditions, the visual performance
      of the subjects was statistically significant for the 3 comparisons, but not
      under photopic conditions. CONCLUSION: High-contrast logMAR chart performed under
      mesopic conditions has the potential to replace visual acuity measured under
      photopic conditions in providing more reliable representation of postoperative
      visual outcomes of LASIK eyes. Eye doctors should consider performing this vision
      test routinely to gauge the success of LASIK surgery.

PMID- 17006582
TI  - Bodies recovered from wells, sewerage systems and pits: what is the cause of
      death?
AB  - INTRODUCTION: The aim of this study was to determine the problems encountered
      during investigations into causes of death in corpses found in wells, sewer
      systems and pits, and to seek solutions to the problems. In fact, wells, sewer
      systems and pits have some common characteristics which may cause the problems.
      They contain water, have a hypoxic/anoxic environment and prevent corpses from
      being recognised. MATERIALS AND METHODS: Based on the data obtained from the 1st
      Specialization Board of the Council of Forensic Medicine, affiliated with the
      Ministry of Justice, we retrospectively reviewed 69 corpses found in wells, sewer
      systems and pits between 1 January 1992 and 31 December 2002. Data on age, sex,
      crime scene and causes of death were obtained and evaluated using the SPSS 11.0
      package programme. RESULTS: Of 69 cases, 69.1% were male and 33.4% were aged 0 to
      10 years. Fifty-eight per cent and 13.1% of the cases were found in wells and
      sewer systems respectively. Forty-three (62.3%) cases were found in a place with
      water. However, 34.9% of them had not drowned. The most frequent cause of death
      was drowning (40.6%). The cause of death was unknown in 18.8% of the cases. 15.9%
      of the corpses were exhumed to determine the cause of death. Twenty-six cases
      (37.7%) had signs of putrefaction and the cause of death was not determined in 9
      cases. Diatom was investigated in 42.0% of the cases (29 cases), but 17 cases did
      not have diatom. CONCLUSION: It is a complicated process to determine the causes
      of death in bodies recovered from wells, pits, water supplies and sewer systems,
      etc. Thorough forensic investigations are required because death may result from
      a wide variety of factors, and lesions on the corpses may undergo some changes
      quickly or can be covered in wells, pits and water supplies. A complete crime
      scene investigation, a thorough autopsy and histopathological, toxicological and
      biochemical examinations would prevent potential problems in determining the
      causes of death in bodies recovered from wells, sewer systems and pits. Almost
      one-third of the bodies recovered from wells, sewer systems and pits were aged 10
      years or younger, which indicates a public health problem. Extra safety
      precautions will help to solve this problem.

PMID- 17006583
TI  - Teleradiology in Singapore--taking stock and looking ahead.
AB  - Teleradiology will have a significant impact on the delivery of healthcare and
      the practice of medicine. In order to ensure a positive outcome, the expected
      benefits, limitations and potential pitfalls of teleradiology must be carefully
      considered. For Singapore, teleradiology can be used to facilitate a quantum leap
      in the standards of radiological services. This can be achieved through the
      development of an integrated, nationwide, high-speed radiology network which will
      allow patients to have access to high-quality and responsive subspecialty
      radiology expertise located throughout the country. If judiciously implemented,
      teleradiology has the potential to propel Singapore radiology to an unprecedented
      level of professional quality and service delivery, and will provide the
      framework for sustainable radiological insourcing from other countries.

PMID- 17006584
TI  - Singapore National Medical Image Resource Centre (SN.MIRC): a world wide web
      resource for radiology education.
AB  - Radiology education is heavily dependent on visual images, and case-based
      teaching files comprising medical images can be an important tool for teaching
      diagnostic radiology. Currently, hardcopy film is being rapidly replaced by
      digital radiological images in teaching hospitals, and an electronic teaching
      file (ETF) library would be desirable. Furthermore, a repository of ETFs deployed
      on the World Wide Web has the potential for e-learning applications to benefit a
      larger community of learners. In this paper, we describe a Singapore National
      Medical Image Resource Centre (SN.MIRC) that can serve as a World Wide Web
      resource for teaching diagnostic radiology. On SN.MIRC, ETFs can be created using
      a variety of mechanisms including file upload and online form-filling, and users
      can search for cases using the Medical Image Resource Center (MIRC) query schema
      developed by the Radiological Society of North America (RSNA). The system can be
      improved with future enhancements, including multimedia interactive teaching
      files and distance learning for continuing professional development. However,
      significant challenges exist when exploring the potential of using the World Wide
      Web for radiology education.

PMID- 17006585
TI  - Updates on the surgical management of paediatric cataract with primary
      intraocular lens implantation.
AB  - With the advent of modern surgical techniques, paediatric cataract has become
      much more manageable. Intraocular lens (IOL) implantation is the standard of care
      for patients over the age of 2 years. The use of IOL in young infants is still
      controversial. In addition, there are still unresolved issues, such as the
      minimum age at which IOL can be safely implanted, IOL power selection and IOL
      power calculation. The current trends in the management of the above challenges
      are discussed. Although numerous reports on the prevention and management of
      posterior capsule opacification have been published, there are ongoing intensive
      debates and research. Long-term postoperative complications like glaucoma and
      rhegmatogenous retinal detachment are problems that cannot be overemphasised and
      these issues are also reviewed.

PMID- 17006586
TI  - Diabetes as a risk factor for periodontal disease: current status and future
      considerations.
AB  - INTRODUCTION: Over the past decade, there has been an emerging interest in the
      interrelationship between systemic conditions and oral health. Diabetes is
      perhaps one of the best documented conditions that have been closely linked with
      periodontal disease. This paper reviews the role of diabetes as a risk factor in
      periodontal disease. The treatment implications in the management of periodontal
      disease as an integral component of diabetes care is also discussed in light of
      the current understanding of the pathogenesis of these 2 chronic conditions.
      MATERIALS AND METHODS: Epidemiological, clinical and laboratory studies examining
      the relationship between diabetes and periodontal diseases were selected from
      both medical and dental journals. RESULTS: The severity of periodontal
      destruction has been shown to be related to the direct and indirect effects of
      glycaemic control, with other factors also being implicated. Although some
      studies have pointed towards a bi-directional relationship between glycaemic
      control and periodontal health, it is still not clear if improvement in
      periodontal health could lead to improved metabolic control. CONCLUSION: Diabetes
      and periodontal disease are closely related in many ways, though the effect of
      periodontal disease on diabetes control remain to be determined, with larger
      intervention studies. In light of the increasing evidence of the relationship
      between diabetes and periodontal disease, management of oral health should form
      an integral part of diabetes management.

PMID- 17006587
TI  - A report of two families with sarcosinaemia in Hong Kong and revisiting the
      pathogenetic potential of hypersarcosinaemia.
AB  - INTRODUCTION: Sarcosinaemia is a rare metabolic disorder which has not been
      reported in Asia. CLINICAL PICTURE: The urine samples of 2 patients were screened
      as a routine metabolic screening offered for patients with mental retardation in
      our hospital. We used gas chromatography-mass spectrometry (GC-MS) which is
      capable of detecting abnormal pattern in amino acids and organic acids. Plasma
      sarcosine level was further quantified by GC-MS. The same methods were used in
      the investigations of asymptomatic family members. Urine examination by GC-MS
      revealed excessive amount of sarcosine in urine (normally undetectable) and their
      plasma sarcosine levels were raised. The 2 differential diagnoses of presence of
      sarcosine in urine--glutaric aciduria type II and folate deficiency--were ruled
      out by the absence of abnormal organic acids in the initial urine screen and by
      normal serum folate level respectively. Screening of the 2 families identified
      excessive sarcosine in urine in 2 siblings, one from each family. However, these
      2 siblings of indexed patients thus identified have no neurological or
      developmental problem. CONCLUSION: Our finding was consistent with the notion
      that sarcosinaemia is a benign condition picked up coincidentally during
      screening for mental retardation.

PMID- 17006588
TI  - Cutaneous and subcutaneous metastases of adenocarcinoma of the colon and rectum.
AB  - INTRODUCTION: The interesting topic of cutaneous and subcutaneous metastasis from
      rectal carcinoma is discussed using 3 cases. CLINICAL PICTURE: The first case was
      a 70-year-old man with T3N2M0 rectal mucinous adenocarcinoma, who developed an
      inflammatory subcutaneous metastasis at the left scapula 2 years after anterior
      resection. The second case was a 51-year-old man with T4N2M0 splenic flexure
      mucinous adenocarcinoma, who developed metastatic disease including a
      subcutaneous secondary to the back. The third case was a 53-year-old woman who
      developed vulval recurrence 10 months after abdomino-perineal resection for a low
      T3N1M0 rectal adenocarcinoma. TREATMENT: All underwent wide resection.
      CONCLUSION: This entity is rare and usually signifies disseminated disease if
      found remote from the resection site and warrants a thorough metastatic work up.
      A high index of suspicion is recommended when encountered with unresolving skin
      lesions in cancer patients.

PMID- 17006589
TI  - Surgically-induced corneal changes following macular translocation with punctate
      retinotomies and chorioscleral infolding (limited macular translocation).
AB  - INTRODUCTION: To report the sequential changes in corneal topography and
      astigmatism following limited macular translocation. CLINICAL PICTURE AND
      TREATMENT: A 45-year-old-man who underwent limited macular translocation for
      idiopathic subfoveal choroidal neovascularisation in the right eye was evaluated
      by corneal topography and manifest refraction preoperatively and serially for 1
      year postoperatively. OUTCOME: An increase in astigmatism with corneal steepening
      along meridians corresponding to the area of chorioscleral infolding was observed
      and this persisted for 1 year after surgery. Vector-analysed astigmatic change
      showed significant surgically induced astigmatism of 2.18 dioptres (D) X 52.9
      degrees, 2.17 D X 57.8 degrees and 2.56 D X 59.1 degrees at 2, 5 and 12 months
      after surgery respectively. CONCLUSION: Surgically induced corneal changes are
      evident after limited macular translocation and may remain up to 1 year after
      surgery.

PMID- 17006590
TI  - 3rd FY Khoo Memorial Lecture--education, professionalism, outsourcing and the
      future of radiology.

PMID- 17006592
TI  - A single-base deletion in soybean flavonol synthase gene is associated with
      magenta flower color.
AB  - The Wm locus of soybean [Glycine max (L.) Merr.] controls flower color. Dominant
      Wm and recessive wm allele of the locus produce purple and magenta flower,
      respectively. A putative full-length cDNA of flavonol synthase (FLS), gmfls1 was
      isolated by 5' RACE and end-to-end PCR from a cultivar Harosoy with purple flower
      (WmWm). Sequence analysis revealed that gmfls1 consisted of 1,208 nucleotides
      encoding 334 amino acids. It had 59-72% homology with FLS proteins of other plant
      species. Conserved dioxygenase domains A and B were found in the deduced
      polypeptide. Sequence comparison between Harosoy and Harosoy-wm (magenta flower
      mutant of Harosoy; wmwm) revealed that they differed by a single G deletion in
      the coding region of Harosoy-wm. The deletion changed the subsequent reading
      frame resulting in a truncated polypeptide consisting of 37 amino acids that
      lacked the dioxygenase domains A and B. Extracts of E. coli cells expressing
      gmfls1 of Harosoy catalyzed the formation of quercetin from dihydroquercetin,
      whereas cell extracts expressing gmfls1 of Harosoy-wm had no FLS activity.
      Genomic Southern analysis suggested the existence of three to four copies of the
      FLS gene in the soybean genome. CAPS analysis was performed to detect the single
      base deletion. Harosoy and Clark (WmWm) exhibited longer fragments, while Harosoy
      wm had shorter fragments due to the single-base deletion. The CAPS marker co
      segregated with genotypes at Wm locus in a F(2) population segregating for the
      locus. Linkage mapping using SSR markers revealed that the Wm and gmfls1 were
      mapped at similar position in the molecular linkage group F. The above results
      strongly suggest that gmfls1 represents the Wm gene and that the single-base
      deletion may be responsible for magenta flower color.

PMID- 17006591
TI  - The cellulose synthase (CESA) gene superfamily of the moss Physcomitrella patens.
AB  - The CESA gene superfamily of Arabidopsis and other seed plants comprises the CESA
      family, which encodes the catalytic subunits of cellulose synthase, and eight
      families of CESA-like (CSL) genes whose functions are largely unknown. The CSL
      genes have been proposed to encode processive beta-glycosyl transferases that
      synthesize noncellulosic cell wall polysaccharides. BLAST searches of EST and
      shotgun genomic sequences from the moss Physcomitrella patens (Hedw.) B.S.G. were
      used to identify genes with high similarity to vascular plant CESAs, CSLAs,
      CSLCs, and CSLDs. However, searches using Arabidopsis CSLBs, CSLEs, and CSLGs or
      rice CSLFs or CSLHs as queries identified no additional CESA superfamily members
      in P. patens, indicating that this moss lacks representatives of these families.
      Intron insertion sites are highly conserved between Arabidopsis and P. patens in
      all four shared gene families. However, phylogenetic analysis strongly supports
      independent diversification of the shared families in mosses and vascular plants.
      The lack of orthologs of vascular plant CESAs in the P. patens genome indicates
      that the divergence of mosses and vascular plants predated divergence and
      specialization of CESAs for primary and secondary cell wall syntheses and for
      distinct roles within the rosette terminal complexes. In contrast to Arabidopsis,
      the CSLD family is highly represented among P. patens ESTs. This is consistent
      with the proposed function of CSLDs in tip growth and the central role of tip
      growth in the development of the moss protonema.

PMID- 17006593
TI  - Self-compatible peach (Prunus persica) has mutant versions of the S haplotypes
      found in self-incompatible Prunus species.
AB  - This study demonstrates that self-compatible (SC) peach has mutant versions of S
      haplotypes that are present in self-incompatible (SI) Prunus species. All three
      peach S haplotypes, S (1), S (2), and S (2m), found in this study encode mutated
      pollen determinants, SFB, while only S (2m) has a mutation that affects the
      function of the pistil determinant S-RNase. A cysteine residue in the C5 domain
      of the S (2m)-RNase is substituted by a tyrosine residue, thereby reducing RNase
      stability. The peach SFB mutations are similar to the SFB mutations found in SC
      haplotypes of sweet cherry (P. avium) and Japanese apricot (P. mume). SFB (1) of
      the S (1) haplotype, a mutant version of almond (P. dulcis) S (k) haplotype,
      encodes truncated SFB due to a 155 bp insertion. SFB (2) of the S (2) and S (2m)
      haplotypes, both of which are mutant versions of the S (a) haplotype in Japanese
      plum (P. salicina), encodes a truncated SFB due to a 5 bp insertion. Thus,
      regardless of the functionality of the pistil determinant, all three peach S
      haplotypes are SC haplotypes. Our finding that peach has mutant versions of S
      haplotypes that function in almond and Japanese plum, which are phylogenetically
      close and remote species, respectively, to peach in the subfamily Prunoideae of
      the Roasaceae, provides insight into the SC/SI evolution in Prunus. We discuss
      the significance of SC pollen part mutation in peach with special reference to
      possible differences in the SI mechanisms between Prunus and Solanaceae.

PMID- 17006594
TI  - Comparative expression profiling in meristems of inbred-hybrid triplets of maize
      based on morphological investigations of heterosis for plant height.
AB  - Heterosis, the superior performance of hybrids as compared to their parental mean
      is an agronomically important phenomenon well-described morphologically. However,
      little is known about its molecular basis. We investigated four genetically
      unrelated maize (Zea mays L.) inbred lines and their F(1) crosses both at the
      phenotype and transcriptome level, focusing on plant height (PHT) component
      traits. Substantial mid-parent heterosis (MPH) was found for all parent-hybrid
      triplets for PHT in the range of 37.9-56.4% in the field and 11.1-39.5% under
      controlled greenhouse conditions. Analyses of heterosis for number and length of
      internodes showed two to three times higher MPH in the field as compared to the
      greenhouse. All three traits exhibited high heritabilities, highest for PHT 95
      98%. Two methods for gene expression quantification were applied. High-density
      cDNA uni-gene microarrays containing 11,827 ESTs were utilized for the selection
      of differentially expressed genes related to heterosis for PHT. For the four
      triplets with eight possible parent-hybrid comparisons we identified 434
      consistently differentially expressed genes with a p < or = 0.05. Microarray
      results were used to verify the dominance/overdominance hypothesis. In our study,
      more than 50% genes showed overdominance, 26% partial dominance, 12.6% complete
      dominance and 10.2% additive gene action. Moreover, more consistently
      differentially expressed genes were detected in related triplets, sharing one
      parent, than in unrelated triplets. Quantitative RT-PCR was applied in order to
      validate microarray results. The role of the differentially expressed genes in
      relation to heterosis for PHT is discussed.

PMID- 17006595
TI  - Characterization of the plant Notchless homolog, a WD repeat protein involved in
      seed development.
AB  - We have isolated a plant NOTCHLESS (NLE) homolog from the wild potato species
      Solanum chacoense Bitt., encoding a WD-repeat containing protein initially
      characterized as a negative regulator of the Notch receptor in animals. Although
      no Notch signaling pathway exists in plants, the NLE gene is conserved in
      animals, plants, and yeast. Overexpression of the plant ScNLE gene in Drosophila
      similarly affected bristle formation when compared to the overexpression of the
      endogenous Drosophila NLE gene, suggesting functional conservation. Expression
      analyses showed that the ScNLE gene was fertilization-induced and primarily
      expressed in ovules after fertilization, mainly in the integumentary tapetum
      (endothelium). Significant expression was also detected in the shoot apex.
      Promoter deletion analysis revealed that the ScNLE promoter had a complex
      modulatory architecture with both positive, negative, and tissue specific
      regulatory elements. Transgenic plants with reduced levels of ScNLE transcripts
      displayed pleitotropic phenotypes including a severe reduction in seed set,
      consistent with ScNLE gene expression pattern.

PMID- 17006596
TI  - Coat protein gene diversity among Chrysanthemum virus B isolates from India.
AB  - The complete coat protein (CP) sequences from 29 Indian isolates of Chrysanthemum
      virus B (CVB) were determined and analysed in relation to other previously
      characterized carlaviruses. The CP genes of the Indian CVB isolates were highly
      heterogeneous, sharing nucleotide sequence identities of 74-98%. Based on
      phylogenetic analyses, the isolates formed three groups potentially representing
      either two or three major CVB strain groupings. Recombination analysis revealed
      at least one definite recombination event involving the exchange of sequences
      between members of different groups. To our knowledge this is the first reported
      evidence of homologous recombination in carlaviruses.

PMID- 17006597
TI  - Evidence for independent segregation of the VP6- and NSP4- encoding genes in
      porcine group A rotavirus G6P[13] strains.
AB  - Molecular characterization of two porcine group A rotavirus strains (HP113 and
      HP140), detected from eastern India, revealed a VP7 closely related to those of
      human G6P[14] strains, VP4 with a borderline P[13] genotype, and VP6 related to
      bovine and human SGI strains rather than porcine SGI and/or SGII group A
      rotaviruses. Both strains had NSP4 and NSP5 of porcine origin. Therefore, to our
      knowledge, the present study is the first report of detection of group A
      rotavirus strains with G6P[13] genotype specificities and provides evidence for
      independent segregation of the VP6- and NSP4-encoding genes in porcine group A
      rotaviruses.

PMID- 17006598
TI  - Infection of soybean by cucumber mosaic virus as determined by viral movement
      protein.
AB  - To characterize the host range determinant of the soybean strain of Cucumber
      mosaic virus (CMV) we analyzed a series of pseudorecombinants and chimeric
      viruses between infectious transcripts from two soybean strains (CMV-SC and CMV
      SD) and an ordinary strain (CMV-Y). CMV-Y could not infect soybeans, even
      locally. Systemic infection of the two soybean-adapted soybean isolates on
      soybean plants mapped to RNA3. Chimeric RNA3s from between CMV-SC and CMV-Y, and
      chimeric RNA3s from between CMV-SC and CMV-SD, were made and inoculated onto wild
      soybean Iwate and soybean cv. Tsurunoko. The 3a region determined the viral
      systemic movement in the plants. In the wild soybean ecotype Hyougo, cell-to-cell
      movement of two different CMV soybean strains, one of which infects systemically
      while the other does not, in the inoculated leaves were almost the same,
      suggesting that the resistance of soybean operates at the level of long-distance
      movement. Our results clearly suggest that movement protein is a host determinant
      of CMV soybean strains.

PMID- 17006599
TI  - Armored RNA as positive control and standard for quantitative reverse
      transcription-polymerase chain reaction assay for rubella virus.
AB  - RV Armored RNA constructed in the laboratory was shown to be resistant to RNase
      and DNase digestion. It could remain stable at 4 degrees C for at least 60 days,
      and was much more stable than RV strain TR23 [corrected] in normal human plasma.
      Therefore it could be used as stable, well-characterized positive control and
      standard for quantitative RT-PCR assay.

PMID- 17006600
TI  - L-methionine as immune supportive supplement: a clinical evaluation.
AB  - The objective of the study was to test L-methioinine as a possible immune
      supportive supplement in HIV infected patients by means of a clinical study. A
      double-blind, placebo-controlled study was designed. The patients (n = 253) from
      four different trial centres were randomly divided into two groups, active and
      placebo, and regularly assessed by clinical and safety parameters. After six
      months from commencement, clinically and statistically significant differences
      were observed. The females of the active treatment group presented with a
      decreased level of decline in their CD4 counts (p = 0.0027), so also the patients
      of Centre 1 (p = 0.0377). All patients were placed onto active treatment after 12
      months and were followed up for 48 months after the trial started. The same
      tendencies could be observed in the group as a whole, with no serious side
      effects directly associated to treatment. The study confirmed the supportive role
      of L-methionine in immune-compromised or deficient patients.

PMID- 17006601
TI  - Free glutamine as a major precursor of brown products and fluorophores in
      Maillard reaction systems.
AB  - Glutamine is one of the most abundant free amino acid found in raw food. In this
      study, the contribution of free glutamine to nonenzymatic browning and
      fluorescence was investigated using an aqueous model system with methylglyoxal.
      The results indicated that glutamine contributed to the Maillard reaction via two
      pathways. First, the hydrolysis of the amide bond of glutamine led to the release
      of ammonia which was implicated in the formation of brown color and fluorescence.
      Among other nitrogen donors tested (asparagine, glutamic acid and urea) our
      results demonstrated that free glutamine was a major source of ammonia during
      heating. When heated at 120 and 180 degrees C, 100% of ammonia was released from
      glutamine after 60 and 10 min, respectively. The second pathway involved a direct
      Maillard reaction with the alpha-amino group of glutamine. Both pathways led to a
      rapid and complete destruction of glutamine when heated in the model systems.
      With reference to the Maillard browning (absorbance at 420 nm) glutamine turned
      out to be the most reactive amine, followed by asparagine, glutamate, ammonia and
      urea. Maximum fluorescence (excitation and emission wavelengths at 330 and 450
      nm, respectively) was also observed with glutamine followed by urea and ammonia.
      Overall this study suggested that free glutamine predominantly contributes to the
      color and fluorescence formations of foodstuffs.

PMID- 17006602
TI  - The effect of taurine on renal ischemia/reperfusion injury.
AB  - Ischemia-reperfusion (I/R) injury is one of the most common causes of renal
      dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing,
      intracellular, free beta-amino acid. It has been demonstrated to have protective
      effects against I/R injuries to tissues other than kidney. The aim of this study
      was to determine whether taurine has a beneficial role in renal I/R injury. Forty
      Wistar-Albino rats were allocated into four groups as follows: sham, taurine,
      I/R, and I/R+taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in
      the groups taurine and I/R+taurine. Renal I/R was achieved by occluding the renal
      arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately
      thereafter, blood was drawn and tissue samples were harvested to measure 1) serum
      levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde
      (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6
      phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3)
      renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine
      administration reduced I/R-induced increases in serum BUN and creatinine, and
      serum and tissue MDA levels (p<0.05). Additionally, taurine lessened the
      reductions in serum and tissue glutathione levels secondary to I/R (p<0.05).
      Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R
      induced P-selectin immunoreactivity (p<0.05). Overall, then, taurine
      administration appears to reduce the injurious effects of I/R on kidney.

PMID- 17006603
TI  - Neuropeptides in anxiety and depression.

PMID- 17006604
TI  - Gene-gene interaction between IL-13 and IL-13Ralpha1 is associated with total IgE
      in Korean children with atopic asthma.
AB  - Interleukin (IL)-13, which is essential for IgE synthesis, mediates its effects
      by binding with a receptor composed of IL-4Ralpha and IL-13Ralpha1. We
      investigated the effects of IL-13 and IL-13Ralpha1 polymorphisms in Korean
      children with asthma, and whether these have been associated with IgE production.
      We enrolled 358 atopic asthmatic, 111 non-atopic asthmatic, and 146 non-atopic
      healthy children. IL-13 and IL-13Ralpha1 genotypes were identified using the PCR
      RFLP method. There was an association between the asthma susceptibility and
      homozygosity for risk allele of IL-13 G+2044A. In children with atopic asthma,
      risk alleles in IL-13 (A-1512C and C-1112T) and IL-13Ralpha1 (A+1398G) showed
      increased total IgE (P=0.012, 0.015 and 0.017, respectively). Three-loci
      haplotype analysis for IL-13 showed that the haplotype composed of -1512C, -1112T
      and +2044A was associated with higher total IgE than other tested haplotypes in
      children with atopic asthma (P=0.003). The gene-gene interaction between risk
      alleles of each IL-13 promoter polymorphism and IL-13Ralpha1 polymorphism was
      associated with higher total IgE in children with atopic asthma (P=0.002, 0.010).
      These findings indicate that the IL-13 G+2044A is associated with asthma
      development and the IL-13 and IL-13Ralpha1 polymorphisms may interact to enhance
      IgE production.

PMID- 17006605
TI  - Molecular analysis of two uncharacterized sequence variants of the VHL gene.
AB  - Mutations in the VHL gene cause von Hippel-Lindau disease, a cancer predisposing
      syndrome characterized by a variety of benign and malignant neoplasms. We report
      the molecular characterization of two sequence variants of the VHL gene: a
      synonymous substitution c.462 A>C in exon 2 and a duplication of 11 bp in the
      promoter region (c.-65_-55dup11). The first variant is a pathogenic mutation
      because, although it does not change the sense of the affected codon, it causes
      skipping of exon 2 in the affected allele by altering the splicing consensus site
      at the 3' end of exon 2. The 11 bp duplication represents a nonpathogenic
      variant. In fact, although it affects a critical region of the VHL promoter, it
      was found in healthy controls, and we show that carrier individuals express both
      VHL alleles at equimolar levels. Our data underline the importance of careful
      evaluation of the potential pathogenicity of sequence variants that may not
      belong to the obvious disease-causing mutation categories, or that affect
      relevant regulatory regions. mRNA analysis will be required to ultimately resolve
      this issue.

PMID- 17006606
TI  - A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of
      advanced gastric adenocarcinoma in a Japanese population.
AB  - Proinflammatory cytokine gene polymorphisms have been demonstrated to associate
      with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well
      investigated due to the possibility that they may alter the IL1B transcription.
      The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the
      nuclear factor of kappa B (NFkappaB) activation, supports cancer development,
      signal transduction in which is mediated by FS-7 cell-associated cell surface
      antigen (FAS) signaling. Based on recent papers describing the prognostic roles
      of the polymorphisms and the NFkappaB functions on cancer development, we sought
      to determine if Japanese gastric cancer patients were affected by the IL1B -31/
      511 and FAS-670 polymorphisms. A case-control study was conducted on incident
      gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control
      subjects (n=271). We observed strong linkage disequilibrium between the T allele
      at -511 and the C allele at -31 and between the C allele at -511 and the T allele
      at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511
      nor FAS-670 polymorphisms showed significantly different risks of gastric
      adenocarcinoma. Though FAS-670 polymorphisms did not show any significant
      difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased
      according to stage (trend P=0.019). In particular, subjects with stage IV had a
      two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype
      compared with stage I subjects. These observations suggest that IL1B-31TT and
      IL1B-511CC are associated with disease progression.

PMID- 17006608
TI  - Treatment of peritoneal carcinomatosis by cytoreductive surgery and
      intraperitoneal hyperthermic chemoperfusion (IHCP): postoperative outcome and
      risk factors for morbidity.
AB  - BACKGROUND: Cytoreductive surgery with limited or extended peritonectomy
      associated with intraperitoneal hyperthermic chemoperfusion (IHCP) has been
      proposed for treatment of peritoneal carcinomatosis (PC) from abdominal
      neoplasms. METHODS: Fifty-nine patients with PC from abdominal neoplasms
      underwent 61 treatments using this technique from January 2000 to August 2005.
      Surgical debulking, completed by partial or total peritonectomy, was performed in
      most cases. In 16 patients with positive peritoneal cytology without macroscopic
      peritoneal disease, IHCP was performed in order to prevent peritoneal recurrence.
      IHCP was carried out throughout the abdominopelvic cavity for 60 minutes using a
      closed abdomen technique. Intra-abdominal temperature ranged between 41 degrees C
      and 43 degrees C; mitomycin C (25 mg/mq) and cisplatin (100 mg/mq) were the
      anticancer drugs generally used, and they were administered with a flow rate of
      700-800 ml/minute. RESULTS: Mean hospital stay was 13 +/- 7 (range 7-49) days.
      Postoperative complications occurred in 27 patients (44.3%); of these, major
      morbidity was observed in 17 (27.9%). The most frequent complications were wound
      infection (9 cases), grade 2 or greater hematological toxicity (5 cases),
      intestinal fistula (5 cases), and pleural effusion requiring drainage (5 cases).
      Reoperation was necessary in 5 patients (8.2%). One patient with multiorgan
      failure died in the postoperative period (mortality rate: 1.6%). Multivariate
      analysis of several variables identified completeness of cancer resection (CCR
      2/3 vs. CCR-0/1, relative risk: 9.27) and age (relative risk: 1.06 per year) as
      independent predictors of postoperative morbidity. Preliminary follow-up data
      indicate that survival probability may be high in patients with ovarian or
      colorectal cancer and low in patients with gastric cancer. CONCLUSIONS: IHCP
      combined with cytoreductive surgery involves a high risk of morbidity, but
      postoperative complications could be resolved favorably in most cases with
      correct patient selection and adequate postoperative care. Tumor residual and
      advanced age significantly increase the risk of morbidity after this procedure.

PMID- 17006609
TI  - Pancreatoduodenectomy for distal cholangiocarcinoma: prognostic impact of lymph
      node metastasis.
AB  - BACKGROUND: The aim of this study was to identify useful prognostic factors in
      patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma. METHODS:
      The records of 36 patients with distal cholangiocarcinoma undergoing
      pancreatoduodenectomy were retrospectively reviewed. Potential
      clinicopathological prognostic factors that may affect survival were examined by
      univariate and multivariate analysis. RESULTS: There was no mortality. Overall
      survival rates were 75%, 54%, and 50% for 1, 3 and 5 years, respectively (median
      survival time, 26 months). Univariate analysis found that age (>== 65 years),
      pancreatic invasion, duodenal invasion, lymph node metastasis, perineural
      invasion and a positive surgical margin were significant predictors of poor
      prognosis (P < 0.05). Furthermore, lymph node metastasis was found to be a
      significant independent predictor of poor prognosis by multivariate analysis (P =
      0.043). Moreover, there were significant differences in the 5-year survival
      between patients with 2 or less involved lymph nodes and those with 3 or more
      positive nodes (P < 0.001). There were no 2-year survivors of the group of
      patients with 3 or more positive nodes. CONCLUSIONS: These results suggest that
      the presence and number of lymph nodes exhibiting metastatic disease might be
      useful in predicting the postsurgical outcome in patients undergoing
      pancreatoduodenectomy for distal cholangiocarcinoma.

PMID- 17006610
TI  - Survival after neoadjuvant therapy compared with surgery alone for resectable
      esophageal cancer in a population-based study.
AB  - BACKGROUND: Esophagectomy remains the standard treatment for resectable
      esophageal cancer, but the cure rate is low. Neoadjuvant therapy has been tried
      in attempts to prolong survival and reduce tumor recurrence. The aim of this
      study was to assess the surgical outcomes with and without neoadjuvant treatment
      for resectable esophageal cancer in a population-based setting. METHODS: All
      1,155 patients treated with esophagectomy for esophageal cancer in Sweden in 1987
      through 2000 with or without neoadjuvant therapy were identified and followed up
      in nationwide registers up to 18 October 2004. Tumor characteristics and response
      to neoadjuvant treatment were obtained from histopathological reports. Hazard
      ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential
      confounding factors were calculated by a Cox proportional hazards regression
      model. RESULTS: Overall survival was similar in the groups with and without
      neoadjuvant therapy (adjusted HR 0.99, 95% CI 0.86-1.16). The 3-year survival
      rates were 34.6% and 32.0%, respectively. Survival was better among the 27.6% of
      the neoadjuvant group with a complete histopathological response (HR 0.71, 95% CI
      0.53-0.94) compared with the surgery only group. Patients without complete
      response to neoadjuvant therapy had seemingly poorer survival (HR 1.10, 95% CI
      0.94-1.29). CONCLUSIONS: Surgical outcomes with and without neoadjuvant therapy
      were equivalent. Only patients with a complete histopathological response after
      neoadjuvant treatment had better survival.

PMID- 17006611
TI  - Subtotal thyroidectomy: a reliable method to achieve euthyroidism in Graves'
      disease. Prognostic factors.
AB  - BACKGROUND: Subtotal thyroidectomy is a widely accepted surgical procedure for
      Graves' disease. The purpose of this work is to evaluate functional long-term
      results and determine predictive prognostic factors of postoperative thyroid
      function. STUDY DESIGN: This is a retrospective study conducted on 202 patients
      with Graves' disease undergoing subtotal thyroidectomy during the period 1979
      2002. Predictive prognostic factors of final thyroid status were investigated by
      logistic ordinal regression, and probability of hypothyroidism during the years
      of follow-up was obtained by the Kaplan-Meier method. RESULTS: Surgery controlled
      hyperthyroidism in 196 out of 202 patients (97%). The probability of hypo-, eu-,
      and hyperthyroidism at 5 years was 62.1%, 35.5%, and 2.4%, respectively. No
      statistical change in thyroid function occurred in the follow-up after 60 months.
      Multivariate analysis by a logistic ordinal regression analysis showed that
      weight of the remnant, age, and gender seemed to influence long-term thyroid
      function. The higher rates of euthyroidism were obtained when the remnant weight
      was between 6 and 8 g. No recurrence or persistence of hyperthyroidism occurred
      with remnant weights under 5 g. CONCLUSIONS: Subtotal thyroidectomy controlled
      hyperfunction symptoms in 97% of our patients. Cure (euthyroidism) of Graves'
      disease patients should be attempted by leaving a thyroid tissue remnant between
      6 and 8 g. Even more significant, our results suggest that euthyroidism rates
      could be improved by leaving a smaller remnant in elderly women and greater
      remnants in young men.

PMID- 17006612
TI  - Lessons learned from initial experience with peritonectomy and intra-peritoneal
      chemotherapy infusion.
AB  - INTRODUCTION: Patients diagnosed with peritoneal carcinomatous usually survive
      for less than 6 months. Cytoreductive surgery allows relief of the obstruction
      and improvement in functional status, while intraperitoneal chemotherapy infusion
      provides high local concentrations of chemotherapeutic agents. Our institutional
      experience is reviewed to assess the selection criteria, peri-operative
      complications, and outcomes. MATERIALS AND METHODS: We carried out a
      retrospective review of nine patients who had undergone aggressive cytoreductive
      surgery and hyperthermic intra- and early post-operative chemotherapy by a single
      surgeon between April 2000 and October 2004. The inclusion criteria were: (1) a
      demonstrated absence of extra-peritoneal and hepatic spread, (2) fitness of the
      patient and ability to tolerate cytoreductive surgery and intra-operative
      chemotherapy, and (3) the presence of a primary tumor originating form the gastro
      intestinal tract (colonic, appendiceal, and gastric primaries). RESULTS: Seven
      women and two men, with a median age of 55 years, were treated. The median
      duration of the operation was 12 hours and 55 minutes. Seven of the nine patients
      required the insertion of at least one chest tube. All patients were monitored in
      the surgical intensive care unit (SICU) for a median of 1 day, started on feeds
      after a median of 6 days, and were hospitalized for a median of 16 days (range:11
      18 days). There was no peri-operative mortality and only one major peri-operative
      complication (11.1%). At the time of analysis, the median follow-up was 16 months
      (range: 2-40 months), and the median disease-free survival was 8 months, with
      four of the nine patients showing no evidence of recurrence. To date, all of the
      patients are still alive. A 1-year survival rate of 100% is also documented.
      CONCLUSIONS: This article describes our initial experience with peritonectomy and
      intra-operative, intra-peritoneal chemotherapy infusion. Our initial problems
      included difficulty with leakage of the chemotherapeutic agents into the thoracic
      cavity that had to be overcome by the early insertion of chest-tubes. With
      appropriate patient selection, cytoreductive surgery with the infusion of intra
      operative chemotherapy can be considered to be a therapeutic option for some
      patients with diffuse peritoneal metastases, and good disease-free and overall
      survival can be achieved with minimal morbidity.

PMID- 17006613
TI  - A systematic review of the efficacy of cesarean section in the preservation of
      anal continence.
AB  - PURPOSE: Elective primary cesarean section is performed largely to avoid maternal
      pelvic trauma that may result in anal incontinence, although its efficacy in this
      regard has not been thoroughly assessed. We perform a systematic review of
      published reports that compare anal incontinence risk by mode of delivery.
      METHODS: PubMed was searched from 1966 through August 2005. Authors were
      contacted for missing data or analyses. Both randomized and nonrandomized reports
      were included. Eligible studies included females having vaginal delivery or
      cesarean section, fecal and/or flatal incontinence was reported as an outcome,
      and risk was calculable from the reported data. Crude data were extracted from
      the reports, as well as reported odds ratios and confidence intervals. In the
      nonrandomized studies, adjusted odds ratios also were extracted and additional
      data obtained from authors to adjust risks for age and parity if not originally
      done. Sensitivity analyses were performed using quality indicators: age and
      parity adjustment, time to continence assessment, and mode of previous delivery.
      RESULTS: Fifteen studies were found eligible, encompassing 3,010 cesarean
      sections and 11,440 vaginal deliveries. The summary relative risk for fecal
      incontinence was 0.91 (95 percent confidence interval, 0.74-1.14). For flatus the
      relative risk was 0.98 (range, 0.86-1.13). The number needed to treat by cesarean
      section was 167 to prevent a single case of fecal incontinence. Five studies were
      judged to be of high quality. In these studies, the summary relative risk was
      0.94 (range, 0.72-1.22) and number needed to treat was 198. CONCLUSIONS: The best
      evidence to assess the efficacy of cesarean section in the prevention of anal
      incontinence would be in randomized trials of average-risk pregnancies with few
      crossovers. In the absence of such trials and based on this review, cesarean
      section does not prevent anal incontinence. This implies that incontinence
      associated with delivery may be more likely incontinence caused by pregnancy.

PMID- 17006616
TI  - Comment on "Pregnancy and delivery following tension-free vaginal tape".

PMID- 17006615
TI  - A decade's experience with vesicovaginal fistula in India.
AB  - A retrospective analysis of 252 cases of vesicovaginal fistulae was done to
      analyse its etio-pathology and management in an Indian population. After a
      thorough evaluation, different techniques of fistula closure were used for repair
      and the results were listed. The main outcome measures were the etiology of the
      fistula, need for tissue interposition and cure rate per repair as well as the
      overall cure rate. We compared our results with literature and concluded that
      simple and small fistulae should be repaired with layered closure. All
      complicated fistulae should be repaired with tissue interposition or tissue
      graft. This is the first study from India compiling 10 years of experience on
      vesicovaginal fistula.

PMID- 17006617
TI  - Inhibition of cell proliferation and induction of apoptosis by genistein in
      experimental hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the leading cause of cancer related deaths in
      the world, with increasing incidence in many developed countries. Epidemiological
      data suggest that consumption of soy products may be associated with a decreased
      risk of cancer. We investigate the effects of genistein on cell proliferation,
      apoptosis and caspase-3 in DEN induced (200 mg/kg body weight; by single
      intraperitoneal injection) and Phenobarbital promoted (0.05% through drinking
      water for 14 successive weeks) cancer-bearing rats. Immunohistochemistry was
      employed to detect cell proliferating markers proliferating cell nuclear antigen
      (PCNA), DNA fragmentation was determined by agarose gel electrophoresis and
      terminal deoxynucleatide transferase dUTP nick labeling (TUNEL) staining and
      caspase by enzyme-linked immunosorbent assay. We found inhibition of cell
      proliferation, induction of apoptosis and activation of caspase-3 in genistein
      treated animals. From these results, we conclude that genistein inhibit cell
      proliferation, induced apoptosis. This activation of caspsase-3 in genistein
      treated liver cancer bearing animals correlated well with its apoptosis inducing
      effect.

PMID- 17006618
TI  - Functional characterization of AATF transcriptome in human leukemic cells.
AB  - The study, addressed to explore the transcriptional expression and regulation of
      Apoptosis-antagonizing transcription factor (AATF) gene within various types of
      human leukemic cell lines, revealed that AATF gene was overexpressed ubiquitously
      in all the leukemic cell lines studied and this upregulation was accompanied by c
      myc gene overamplification in these cells. Downregulation of AATF gene
      transcription within leukemic cells not only resulted in the downregulation of c
      myc gene and vice-versa but also contributed to apoptosis leading to cell death.
      Further, the link between AATF expression and leukemic cellular apoptosis
      involved PI3K/Akt pathway. Based on these results we propose that AATF gene may
      be of crucial importance in maintaining the leukemic state of a cell compartment
      through its ability to initiate cell proliferation coupled with repression of
      cellular apoptosis.

PMID- 17006619
TI  - The role of a heat shock protein from V. cholerae 0139 in the gut immune
      response.
AB  - An immunodominant heat shock protein (Hsp 24) was purified from Vibrio cholerae
      O139 at 42 degrees C and used as an immunomodulator for studying the gut immune
      response. T cell clone and T cell line specific for the Hsp 24 were generated
      from the lymphocytes of lamina propria and intra-epithelial lymphocytes of mice
      orally infected with V. cholerae O139, respectively. The T cell clone was TCR
      alphabeta(+), CD4(+) and appeared to play an important role in the functioning of
      gut B-lymphocytes. The T cell line had heterogenous population of CD8+ and CD4+
      cells, most of which were found to be TCR alphabeta(+) and a minor population was
      TCR gammadelta(+). The lymphokine profile of T cell line showed IFN-gamma to be
      the most abundant lymphokine followed by IL-2 and IL-4. The possible involvement
      of alternative pathway of activation for T cell clone was also addressed in this
      study. The splenocytes showed an up-regulation of their CD2 receptor expression
      on stimulation with the Hsp-24. The pattern of lymphokines released by
      splenocytes stimulated with the Hsp-24 showed no particular cell type to be
      responsible for mounting immune response. Thus, there is involvement of both,
      mucosal and peripheral arm of the immune system.

PMID- 17006620
TI  - Succinic acid monoethyl ester, a novel insulinotropic agent: effect on lipid
      composition and lipid peroxidation in streptozotocin-nicotin-amide induced type 2
      diabetic rats.
AB  - Succinic acid monoethyl ester (EMS) is recently proposed as an insulinotropic
      agent for the treatment of non-insulin dependent diabetes mellitus. Oxidative
      stress has been suggested to be a contributory factor in the development and
      complications of diabetes. In the present study the effect of EMS and Metformin
      on plasma glucose, insulin, serum and tissue lipid profile, lipoproteins and
      lipid peroxidation in streptozotocin-nicotinamide induced type 2 diabetic model
      was investigated. The carboxylic nutrient EMS was administered intraperitonially
      (8 micromol/g body weight) to streptozotocin diabetic rats for 30 days. The
      levels of thiobarbituric acid reactive substances (TBARS) and hydroperoxides in
      liver and kidney and serum and tissue lipids [cholesterol, triglycerides,
      phospholipids and free fatty acids] and very low density lipoprotein-cholesterol
      (VLDL-C) and low density lipoprotein-cholesterol (LDL-C), were significantly
      increased in diabetic rats, whereas the levels of high-density lipoprotein
      cholesterol (HDL-C) and antiatherogenic index (AAI) (ratio of HDL to total
      cholesterol) were significantly decreased. The effect of EMS was compared with
      metformin, a reference drug. Treatment with EMS and metformin resulted in a
      significant reduction of plasma glucose with increase plasma insulin in diabetic
      rats. EMS also resulted in a significant decrease in serum and tissue lipids and
      lipid peroxidation products. These biochemical observations were supplemented by
      histopathological examination of liver and kidney section. Our results suggest
      the possible antihyperlipidemic and antiperoxidative effect of EMS apart from its
      antidiabetic effect.

PMID- 17006621
TI  - Multiple variations of the hepatobiliary vasculature including double cystic
      arteries, accessory left hepatic artery and hepatosplenic trunk: a case report.
AB  - Anatomical variations in the origins and branching patterns of the hepatobiliary
      arterial system may be encountered during both conventional surgical and
      laparoscopic cholecystectomy. We report a rare case of double cystic arteries
      arising from both the right hepatic artery and the proximal part of the posterior
      superior pancreaticoduodenal artery. Additional variations consisting of an
      accessory left hepatic artery arising from a left gastric which in turn arose
      from the descending aorta superior to the origin of the celiac trunk and a small
      left hepatic artery arising from the hepatic proper artery were also noted. The
      celiac trunk bifurcated into the splenic artery and the common hepatic artery
      forming a hepatosplenic or lienohepatic trunk. The possible clinical implications
      are discussed.

PMID- 17006622
TI  - Laparoscopic repair of recurrent childhood inguinal hernias after open
      herniotomy.
AB  - BACKGROUND: Open repair of recurrent paediatric inguinal hernias (IH) is
      difficult and there is definite risk of damaging the vas deferens and testicular
      vessels during dissection of the previous open herniotomy field. Laparoscopic
      repair (LR) has the benefit of avoiding the previous operative site. METHOD:
      Records of patients with recurrent IH that had LR after open repair were reviewed
      and evaluated retrospectively. The results were compared with data from cases in
      which the LR method was used in the initial IH repair. RESULTS: From September
      2002 to October 2005, four boys and one girl (mean age 58.8 months) were treated
      in our institution for recurrent IH after open repair. Operative time, success
      rate and complications did not show any statistically significant difference when
      compared with our previous prospectively collected data for primary repairs.
      CONCLUSION: Laparoscopic repair is the preferred operation for recurrent
      childhood IH after open repair.

PMID- 17006623
TI  - Occult hernias and bilateral endoscopic total extraperitoneal inguinal hernia
      repair: is there a need for prophylactic repair? : Results of endoscopic
      extraperitoneal repair over a period of 10 years.
AB  - BACKGROUND: An advantage of the endoscopic total extraperitoneal approach over
      the conventional hernia repair is detection of an unsuspected, asymptomatic
      hernia on the contralateral side. A high incidence of occult contralateral
      hernias has been reported in the literature. However, few studies have examined
      the incidence of development of a hernia on the healthy side evaluated previously
      during an endoscopic unilateral hernia repair. This study aims to evaluate the
      incidence of development of a contralateral hernia after a previous bilateral
      exploration. The need for a prophylactic contralateral repair is also addressed.
      PATIENTS AND METHODS: We retrospectively reviewed the results of 822 endoscopic
      total extraperitoneal inguinal hernia repairs done in 634 patients over a period
      of 10 years from May 1993 to 2003. Incidence of hernia undetected clinically and
      during previous contralateral repair was assessed over a follow up period ranging
      from 10 to 82 months. RESULTS: About 7.97% of bilateral hernias were clinically
      occult hernias. Only 1.12% of unilateral hernia repairs (who had undergone a
      contralateral evaluation at surgery) subsequently developed a hernia on the other
      side. CONCLUSIONS: The endoscopic approach to inguinal hernia repair is an
      excellent tool to detect and treat occult contralateral hernias. The incidence of
      hernia occurring at the contralateral side after a previous bilateral exploration
      is low, hence a prophylactic repair on the contralateral side is not recommended
      on a routine basis.

PMID- 17006624
TI  - Laparoscopic repair of late presenting congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia usually presents in the neonatal period, with
      delayed presentation being uncommon. Traditionally repair was performed by
      laparotomy or thoracotomy. We have performed laparoscopic repair of a previously
      undiagnosed congenital diaphragmatic hernia that presented acutely in a 10-year
      old male. Laparoscopic repair of late-presenting congenital diaphragmatic hernia
      is a safe and effective approach even in an emergency. The laparoscopic approach
      has advantages including reduced hospital stay, excellent visualisation of the
      defect even for obese patients, and improved cosmesis.

PMID- 17006625
TI  - The biology of hernias and the abdominal wall.
AB  - The fundamental mechanism for hernia formation is loss of the mechanical
      integrity of abdominal wall structural tissue that results in the inability to
      offset and contain intra-abdominal forces during valsalva and loading of the
      torso. There is evidence that genetic or systemic extracellular matrix disorders
      may predispose patients to hernia formation. There is also evidence that acute
      laparotomy wound failure leads to hernia formation and increases the risk of
      recurrent hernia disease. It may be that hernia formation is a heterogeneous
      disease, not unlike cancer, where one population of patients express an
      extracellular matrix defect leading to primary hernia disease, while other
      subsets of patients acquire a defective, chronic wound phenotype following failed
      laparotomy and hernia repairs. It is evident that an improved understanding of
      structural tissue matrix biology will lead to improved results following
      abdominal wall reconstructions.

PMID- 17006626
TI  - Effective creases and contact angles between membrane domains with high
      spontaneous curvature.
AB  - We show that the short-scale elastic distortions that are excited in the vicinity
      of the joint between different lipidic membrane domains (at a scale of
      approximately 10nm) may produce a "crease" from the point of view of the standard
      elastic description of membranes, i.e., an effective discontinuity in the
      membrane slope at the level of Helfrich's theory. This "discontinuity" may be
      accounted for by introducing a line tension with an effective angular dependence.
      We show that domains bearing strong spontaneous curvatures, such as biological
      rafts, should exhibit creases with a finite contact angle, almost prescribed,
      corresponding to a steep extremum of the line energy. Finite contact angles might
      also occur in symmetric membranes from the recruitment of impurities at the
      boundary.

PMID- 17006628
TI  - Specific cleavage of insulin-like growth factor-binding protein-1 by a novel
      protease activity.
AB  - Insulin-like growth factor-binding protein-1 (IGFBP-1) is secreted in a highly
      phosphorylated form that binds IGF-I with high affinity and is resistant to
      proteolysis. We have purified IGFBP-1-specific protease activity from the urine
      of an individual with multiple myeloma. This protease efficiently cleaves both
      phosphorylated and non-phosphorylated IGFBP-1 at Ile130-Ser131, generating
      fragments that together have higher association and dissociation rates for IGFs
      compared with intact IGFBP-1. The proteolytic fraction contained azurocidin, a
      protease homologue hitherto considered inactive. After cleavage of IGFBP-1, there
      was a lower affinity, but higher capacity for IGF-I binding, suggesting both N-
      and C-terminal fragments may interact with ligand independently. There was
      decreased inhibition of IGF-II-stimulated cell growth and glucose uptake. Alone,
      proteolysed IGFBP-1 stimulated glucose uptake in muscle. We conclude that
      specific cleavage of IGFBP-1 at target tissues is important in cellular growth
      and metabolism and opens novel strategies for targeting IGFBP-1 in treatment of
      disease.

PMID- 17006627
TI  - Characterization of apoptosis induced by marine natural products in non small
      cell lung cancer A549 cells.
AB  - The effects of different marine derived agents were studied in A549 cell growth.
      These drugs induced cell cycle arrest at the G2-M phase associated with the up
      regulation of GADD45alpha-gamma and down-regulation of c-Myc. In treated cells,
      GADD45alpha-gamma and c-Myc were up- and down-regulated, respectively. A cascade
      of events leading to apoptotic mitochondrial 'intrinsic' pathway was observed in
      treated cells: (1) dephosphorylation of BAD serine136; (2) BAD dissociation from
      14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4)
      caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor
      prevented the formation of cleavage products and, in turn, apoptosis was
      inhibited through a p53-independent mechanism. Moreover, these compounds did not
      activate NF-kappaB. Our findings may offer new insights into the mechanisms of
      action of these agents in A549 cells. The better understanding of their effects
      might be important to fully exploit the potential of these new drugs.

PMID- 17006629
TI  - p27 small interfering RNA induces cell death through elevating cell cycle
      activity in cultured cortical neurons: a proof-of-concept study.
AB  - Recent research has demonstrated that cell cycle-associated molecules are
      activated in multiple forms of cell death in mature neurons, and raised a
      hypothesis that unscheduled cell cycle activity leads to neuronal cell death. But
      there is little evidence that changes in endogenous level of these molecules are
      causally associated with neuronal cell death. Here we transfected small
      interfering RNA (siRNA) targeting cyclin-dependent kinase (CDK) inhibitor p27,
      which plays an important role in cell cycle arrest at G1-S phase, into cultured
      cortical neurons. Transfection of p27 siRNA reduced neuronal viability in a time
      dependent manner. p27 siRNA induced phosphorylation of retinoblastoma protein
      (Rb), a marker of cell cycle progression at late G1 phase. Moreover,
      phosphorylation of Rb and neuronal cell death provoked by p27 siRNA were
      abrogated by pharmacological CDK inhibitors, olomoucine and purvalanol A. Our
      data demonstrate that a decrease in endogenous p27 induces neuronal cell death
      through elevating cell cycle activity.

PMID- 17006630
TI  - Peduncular hallucinosis: a syndrome of impaired reality monitoring.
AB  - Peduncular hallucinosis (PH) is a syndrome of hallucinations and brainstem
      symptoms which has only been described in single case reports. A detailed
      analysis of five patients was undertaken to investigate the clincial
      characteristics, hallucinations and behavioural abnormalities of PH in greater
      detail. Frequent clinical symptoms were oculomotor disturbances, impaired
      arousal, dysarthria and ataxia. In the chronic stage, sleep-wake cycle
      disturbances were common. Hallucinations were naturalistic, complex, scenic,
      mostly visual, but also combined visual-acoustic or visual-tactile and recurred
      stereotypically over months. Patients experienced their hallucinations as genuine
      and were unable to discriminate their percepts from reality. Neuropsychological
      testing disclosed severe impairments of episodic memory, occasionally coupled
      with confabulatory behaviour. By contrast, memory for hallucinations remained
      intact. Deficits of attentional and executive functions were found in a subgroup
      of patients. Associated abnormal behaviours were common, comprising confusion,
      delusional misidentification for persons and places, and loss of disease
      awareness. PH appeared after focal lesions in various regions, such as the
      midbrain, thalamus and pons. These findings document that subcortical, brainstem
      related hallucinations are vivid, recurring percepts that have a strong
      naturalistic character and are often associated with cognitive and behavioural
      abnormalities. It seems likely that brainstem hallucinosis is caused by damage to
      ascending reticular systems and thalamocortical circuits. Available observations
      suggest that PH compromises cognitive functions which enable us to differentiate
      between illusionary percepts and reality, a reality monitoring system.

PMID- 17006631
TI  - Essential tremor prevalence is low in Arabic villages in Israel: door-to-door
      neurological examinations.
AB  - OBJECTIVE: To estimate the prevalence of essential tremor (ET) in Arabic villages
      of Wadi Ara. BACKGROUND: The prevalence ET which is higher than Parkinson's
      disease in North America and Europe, differs according to study population and
      methodology. Since hospital record based epidemiology carries referral bias and
      might provide low estimates of ET prevalence, we carried a population based
      survey. METHODS: This door-to-door survey comprised the Arabic villages of Wadi
      Ara in Northern Israel. Consecutive residents who agreed to participate in the
      study and were older than 64 years at prevalence day, underwent neurological
      examination. Medical and family history, medication and response to medication
      were recorded. RESULTS: Of the 444 subjects that were approached, 428 agreed to
      participate in the study (refusal rate 3.6%). Four were excluded owing to severe
      systemic disease. The study population consisted of 424 subjects (54% men, mean
      age 74+/-7 years). A clearly oscillatory action tremor of moderate amplitude was
      observed in 8 patients (age 75+/-7 years). Six patients had another possible
      cause of tremor. The prevalence of ET was calculated as 1.89% (95% CI 1.76-2.0)
      when all tremor cases were accepted as possible ET and 0.47% (95 CI 0.43-0.52)
      when patients with other causes of tremor were excluded. CONCLUSIONS: The
      prevalence of ET in Arabic villages of Wadi Ara is low.

PMID- 17006632
TI  - Intravenous immunoglobulins in paraneoplastic brainstem encephalitis with anti-Ri
      antibodies.

PMID- 17006633
TI  - Effects of anesthesia on echocardiographic assessment of left ventricular
      structure and function in rats.
AB  - Echocardiography is an essential diagnostic tool for accurate noninvasive
      assessment of cardiac structure and function in vivo. However, the use of
      anesthetic agents during echocardiographic studies is associated with alterations
      in cardiac anatomical and functional parameters. We sought to systematically
      compare the effects of three commonly used anesthetic agents on echocardiographic
      measurements of left ventricular (LV) systolic and diastolic function, LV
      dimensions, and LV mass in rats. Adult male Fischer 344 rats underwent
      echocardiographic studies under pentobarbital (PB, 25 mg/kg i.p.) (group I, n =
      25), inhaled isoflurane (ISF, 1.5%) (group II, n = 25),or ketamine/xylazine (K/X,
      37 mg/kg ketamine and 7 mg/kg xylazine i.p.) (group III, n = 25) anesthesia in a
      cross-over design. Echocardiography was also performed in an additional group of
      unanesthetized conscious rats (group IV, n = 5). Postmortem studies were
      performed to validate echocardiographic assessment of LV dimension and mass. Rats
      in group I exhibited significantly higher LV ejection fraction, fractional
      shortening, fractional area change, velocity of circumferential fiber shortening
      corrected for heart rate, and heart rate as compared with groups II and III. LV
      end-diastolic volume, end-diastolic diameter, and cross-sectional area in
      diastole were significantly smaller in group I compared with groups II and III.
      Cardiac output was significantly lower in group III compared with groups I and
      II. Postmortem LV mass measurements correlated well with echocardiographic
      estimation of LV mass for all anesthetic agents, and the correlation was best
      with PB anesthesia. Limited echocardiographic data obtained in conscious rats
      were similar to those obtained under PB anesthesia. We conclude that compared
      with ISF and K/X anesthesia, PB anesthesia at a lower dose yields
      echocardiographic LV structural and functional data similar to those obtained in
      conscious rats. In addition, PB anesthesia also facilitates more accurate
      estimation of LV mass.

PMID- 17006634
TI  - Alterations in the endothelial G-protein coupled receptor pathway in epicardial
      arteries and subendocardial arterioles in compensated left ventricular
      hypertrophy.
AB  - The present study was designed to compare alterations of endothelium-dependent
      vasorelaxation in coronary epicardial arteries and subendocardial arterioles
      occurring in left ventricular hypertrophy (LVH) secondary to 60 days of aortic
      banding in a porcine model. Development of LVH was documented by echocardiogram
      and the endothelial function of subendocardial and epicardial vessels was studied
      by constructing concentration-response curves in a pressure myograph and standard
      organ chambers, respectively. 5-HT induced relaxations were reduced (p<0.05) in
      both vessel types isolated from pigs with LVH. Dilations of subendocardial
      arterioles and epicardial vessels to UK14304 were depressed by LVH. In the
      presence of Nomega-nitro-L-arginine (L-NNA), EDHF solely accounts for BK-induced
      relaxations; it fully compensates for the loss of NO in arterioles, but only
      partially in epicardial arteries isolated from LVH swine. Endothelium-independent
      relaxations induced by SNP were not altered in both vessel types from the LVH
      group. In a porcine model of LVH secondary to 60 days of aortic banding, the
      associated coronary endothelial dysfunction preferentially involves Gi-protein
      mediated relaxations in arterioles and arteries but also affects Gq-protein
      mediated relaxations in epicardial coronary arteries.

PMID- 17006635
TI  - Real-time vascular interventional magnetic resonance imaging: the future of
      aortic stent-graft placement?
AB  - Endovascular stent-graft placement is emerging as a promising alternative to
      medical and surgical treatment of patients with diseases of the descending
      thoracic and abdominal aorta. Precise placement of the stentgraft, which is
      currently performed under x-ray control, remains, however, challenging as there
      are several shortcomings to fluoroscopic guidance beyond that related to the
      harmful effect of radiation exposure and nephrotoxic contrast media. While
      transesophageal echocardiography and intravascular ultrasound have been used as
      adjunct imaging modalities during endovascular stent-graft procedures to overcome
      the limitations of angiography, these techniques have not mitigated the need for
      fluoroscopy. Magnetic resonance imaging (MRI) guidance of vascular interventional
      procedures offers several potential advantages over fluoroscopy-guided
      techniques, including image acquisition in any desired orientation, superior 3D
      soft-tissue contrast with simultaneous visualization of the interventional
      device, absence of ionizing radiation, and avoidance of nephrotoxic contrast
      media. Magnetic resonance imaging is often used for pre-operative diagnosis of
      aortic disease and can provide all relevant information for the planning of
      endovascular stent-graft procedures as well as for accurate and immediate post
      interventional evaluation. However, visualization of interventional instruments
      by MRI has proven to be the chief obstacle. This article will review current
      approaches that have been developed for depicting vascular instruments by MRI and
      will also discuss the first experimental experiences with MRI-guided endovascular
      stent-graft placement in a swine model of aortic dissection.

PMID- 17006636
TI  - Canal wall reconstruction and mastoid obliteration with composite multi-fractured
      osteoperiosteal flap.
AB  - We used inferior pedicled composite multi-fractured osteoperiosteal flap (CMOF),
      our original and new surgical approach, to obliterate the mastoid cavity and
      reconstruct the external auditory canal (EAC) to prevent the open cavity
      problems. CMOF was used to obliterate the mastoid cavity and reconstruct the EAC
      in 24 patients (13 women, 11 men; age span 12-51 years) who underwent radical
      mastoidectomy to treat the chronic otitis media between 1998 and 2004. Small
      meatoplasty was done in all 24 patients to relieve their aesthetical concerns.
      Temporal bone CT scanning was done to observe the neo-osteogenesis in the
      mastoidectomy cavity and the CMOF, and the EAC volume was measured
      postoperatively. All our patients were followed-up for 2 years. The
      epithelization of the new EAC in our patients was complete at the end of the
      second month. Cholesteatoma, granulation, and recurrence of osteitis did not
      occur in any of the patients. We saw the new bone formation filling the mastoid
      cavity in the postoperative temporal bone CT scanning images. The mean volume of
      the new EAC on the 24th month was 1.83 +/- 0.56 cm(3). We had an almost natural
      EAC, which owed its existence to the neo-osteogenesis that grows behind the CMOF,
      which we use to obliterate the mastoid cavity and to reconstruct the EAC.

PMID- 17006637
TI  - A study on the prognostic significance of qualitative olfactory dysfunction.
AB  - We investigated the frequency and prognostic significance of qualitative
      olfactory dysfunction (parosmia, phantosmia) in a retrospective patient based
      study. A total of 392 patients with impairment of olfaction were tested at least
      two times for their olfactory function using the "Sniffin' Sticks". The mean
      interval between the first and the last test was 11 months. At the first visit
      34% of all patients reported parosmia. Parosmia was most frequent in patients
      with postinfectious olfactory loss (56%), and less frequent in idiopathic,
      posttraumatic, sinunasal disease with frequencies of 10, 14, and 28%,
      respectively. In contrast, only 12% of all patients had phantosmias, with no
      significant differences between the patient groups. Improvement of olfactory
      function was found in 23% of all patients (n = 90). Pre-existing parosmia or
      phantosmia had no significant effect on recovery rate. Regarding qualitative
      olfactory dysfunction, 29% of those patients reporting parosmia reported relief
      of this symptom after an average of 12 months, whereas 53% of phantosmic patients
      lost phantosmia during the observation period. Although it has been suggested
      that olfactory distortion s could be regarded as an indicator of early recovery
      of decreased olfactory sensitivity, the current data indicate that occurrence of
      parosmia or phantosmia has little prognostic value. Phantosmia disappears at a
      faster rate than parosmia. These insights into qualitative olfactory dysfunction
      are regarded to be significant in the counseling of patients with olfactory loss.

PMID- 17006638
TI  - Galactosylation of IgG from rheumatoid arthritis (RA) patients--changes during
      therapy.
AB  - It is well documented that serum IgG from rheumatoid arthritis (RA) patients
      exhibits decreased galactosylation of its conservative N-glycans (Asn-297) in CH2
      domains of the heavy chains; it has been shown that this agalactosylation is
      proportional to disease severity. In the present investigation we analyzed
      galactosylation of IgG derived from the patients using a modified ELISA-plate
      test, biosensor BIAcore and total sugar analysis (GC-MS). For ELISA and BIAcore
      the binding of IgG preparations, purified from the patients' sera, to two
      lectins: Ricinus communis (RCA-I) and Griffonia simplicifolia (GSL-II) was
      applied. Based on ELISA-plate test an agalactosylation factor (AF, a relative
      ratio of GSL-II/RCA-I binding) was calculated, which was proportional to actual
      disease severity. Repeated testing of several patients before and after treatment
      with methotrexate (MTX) alone or in combination with Remicade (a chimeric
      antibody anti-TNF-alpha) supplied results indicating an increase of IgG
      galactosylation during the treatment. This introductory observation suggests that
      IgG galactosylation may be an additional indicator of the RA patients'
      improvement.

PMID- 17006639
TI  - Kinetic properties and substrate specificities of two recombinant human N
      acetylglucosaminyltransferase-IV isozymes.
AB  - N-acetylglucosaminyltransferase (GnT)-IV catalyzes the formation of the
      GlcNAcbeta1-4 branch on the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of
      N-glycans. Two human GnT-IV isozymes (GnT-IVa and GnT-IVb) had been identified,
      which exhibit different expression profiles among human tissues and cancer cell
      lines. To clarify the enzymatic properties of the respective enzymes, their
      kinetic parameters were determined using recombinant full-length enzymes
      expressed in COS7 cells. The K (m) of human GnT-IVb for UDP-GlcNAc was estimated
      to be 0.24 mM, which is 2-fold higher than that of human GnT-IVa. The K (m)
      values of GnT-IVb for pyridylaminated (PA) acceptor sugar chains with different
      branch numbers were 3- to 6-fold higher than those of GnT-IVa. To compare
      substrate specificities more precisely, we generated recombinant soluble enzymes
      of human GnT-IVa and GnT-IVb with N-terminal flag tags. Both enzymes showed
      similar substrate specificities as determined using fourteen PA-sugar chains.
      They preferred complex-type N-glycans over hybrid-types. Among the complex-type N
      glycans tested, the relative activities of both enzymes were increased in
      proportion to the number of GlcNAc branches on the Man alpha1-6 arm. The Man
      alpha1-6 arm of the acceptors was not essential for their activities because a
      linear pentasaccharide lacking this arm, GlcNAcbeta1-2Manalpha1-3Manbeta1
      4GlcNAcbeta1-4 GlcNAc-PA, was a substrate for both enzymes. These results
      indicate that human GnT-IVb exhibits the same acceptor substrate specificities as
      human GnT-IVa, although GnT-IVb has lower affinities for donors or acceptors than
      GnT-IVa. This suggests that GnT-IVa is more active than GnT-IVb under
      physiological conditions and that it primarily contributes to the biosynthesis of
      N-glycans.

PMID- 17006641
TI  - Unique disialosyl gangliosides from salmon kidney: characterization of
      V3alphaFuc, IV3betaGalNAc, II3(alphaNeuAc)2-Gg4Cer and its analogue with 4-O
      acetyl-N-acetylneuraminic acid.
AB  - Four unidentified acidic glycolipids (X3-X6) were isolated from the kidney of the
      Pacific salmon on an anion exchange column and by high performance liquid
      chromatography using a silica bead (Iatrobeads) column. Based on methylation
      analysis, chemical and enzymatic degradation, proton nuclear magnetic resonance
      spectroscopy and mass spectrometry, the glycon structure of X5 and X6 was
      identified as a unique disialosyl fucosyl-N-acetylgalactosaminyl ganglio-N
      tetraose:Fucalpha3GalNAcbeta3Galbeta3GalNAcbeta4[NeuAcalpha8NeuAcalpha3]
      Galbeta4Glcbeta1Cer. NMR showed that X3 and X4 were analogues of X5 and X6 and
      contained O-acetyl groups on C4 of the outer N-acetylneuraminic acid, first
      disialosyl gangliosides containing 4-O-acetyl-N-acetylneuraminic acid. The
      ceramides of X3 and X5 contained predominantly C24: 1, and X4 and X6 contained
      saturated fatty acids (C14: 0, C16: 0 and C18: 0), whereas the long chain base
      was exclusively sphingenine. The concentrations of X3 and X4 were 0.13 and 0.16
      nmol/g of kidney respectively and those of X5 and X6, were 0.07 nmol/g each.

PMID- 17006640
TI  - Utility of pentose colorimetric assay for the purification of potato lectin, an
      arabinose-rich glycoprotein.
AB  - Potato lectin (Solanum tuberosum agglutinin, STA) is an unusual glycoprotein
      containing approximately 50% carbohydrates by weight. Of the total carbohydrates,
      92% is contributed by L: -arabinose, which are O-linked to hydroxyproline
      residues. The ferric chloride-orcinol assay (Bial's test), which is specific for
      pentoses has so far been used only for the determination of free pentoses in
      biological samples. However, this colorimetric assay has not been used for the
      detection of pentoses in bound form as it occurs in Solanaceae lectins (potato,
      tomato, and Datura lectins). Utilizing the pentose colorimetric assay for
      monitoring the presence of potato lectin, a simpler and shorter procedure for the
      purification of this lectin from potato tubers has been developed. The yield of
      potato lectin (1.73 mg per 100 g potato tuber) is twice compared to the yields
      reported in earlier procedures. Although potato lectin is well known for its
      specificity to free trimers and tetramers of N-acetyl-D: -glucosamine (GlcNAc),
      it possesses a similar specificity to the core (GlcNAc)(2) of N-linked
      glycoproteins. The utilization of the pentose assay in the purification of
      arabinose-rich lectins/agglutinins obviates the necessity for the use of
      agglutination assay in the various purification steps. The pentose assay appears
      to be a simple and convenient colorimetric assay for detecting any pentose-rich
      glycoprotein in plant extracts. The utility of the pentose assay appears to have
      a significant potential in the detection of hydroxyproline-rich glycoproteins
      (HRGPs), which are generally O-arabinosylated.

PMID- 17006642
TI  - Transferase and hydrolytic activities of the laminarinase from Rhodothermus
      marinus and its M133A, M133C, and M133W mutants.
AB  - Comparative studies of the transglycosylation and hydrolytic activities have been
      performed on the Rhodothermus marinus beta-1,3-glucanase (laminarinase) and its
      M133A, M133C, and M133W mutants. The M133C mutant demonstrated near 20% greater
      rate of transglycosylation activity in comparison with the M133A and M133W
      mutants that was measured by NMR quantitation of nascent beta(1-4) and beta(1-6)
      linkages. To obtain kinetic probes for the wild-type enzyme and Met-133 mutants,
      p-nitrophenyl beta-laminarin oligosaccharides of degree of polymerisation 2-8
      were synthesized enzymatically. Catalytic efficiency values, k (cat)/K (m), of
      the laminarinase catalysed hydrolysis of these oligosaccharides suggested
      possibility of four negative and at least three positive binding subsites in the
      active site. Comparison of action patterns of the wild-type and M133C mutant in
      the hydrolysis of the p-nitrophenyl-beta-D-oligosac- charides indicated that the
      increased transglycosylation activity of the M133C mutant did not result from
      altered subsite affinities. The stereospecificity of the transglycosylation
      reaction also was unchanged in all mutants; the major transglycosylation products
      in hydrolysis of p-nitrophenyl laminaribioside were beta-glucopyranosyl-beta-1,3
      D-glucopy- ranosyl-beta-1,3-D-glucopyranose and beta-glucopyranosyl-beta-1, 3-D
      glucopyranosyl-beta-1,3-D-glucpyranosyl-beta-1,3-D- glucopyranoxside.

PMID- 17006643
TI  - Detection of oligosaccharide ligands for hepatocyte growth factor/scatter factor
      (HGF/SF), keratinocyte growth factor (KGF/FGF-7), RANTES and heparin cofactor II
      by neoglycolipid microarrays of glycosaminoglycan-derived oligosaccharide
      fragments.
AB  - Neoglycolipid technology is eminently adaptable for microarray design for high
      throughput detection and specificity assignments of carbohydrate-protein
      interactions. Dermatan sulfate (DS) is known to play an important role because of
      its ability to bind growth factors as well as chemokines and to modulate their
      biological activities during inflammation and response to injury. We prepared
      various iduronic acid-rich fragments from DS by complete digestion with
      chondroitinase ACI, and investigated whether the DS-binding proteins, such as
      HGF/SF, RANTES, KGF/FGF-7 and HCII, can detect their oligosaccharide ligands in a
      neoglycolipid microarray. First, a comparison of the intensity of binding signals
      obtained from chondroitin oligosaccharides with those of heparin oligosaccharides
      showed that our microarray system is feasible not only to single-out the
      oligosaccharide ligands, but also to detect the difference between an intrinsic
      interaction unrelated only to electrostatic interaction and non-specific
      electrostatic interaction. Second, HGF/SF, KGF/FGF-7 and HCII showed preferential
      binding to iduronic acid-rich fragments of DS oligosaccharides that are greater
      than 8-mers in lengths. In contrast, RANTES binding seemed to depend only on the
      negative charges; their binding intensity towards the DS oligosaccharides was
      somewhat stronger than the binding of HGF/SF, KGF/FGF-7 and HCII. Third, the use
      of polyvinylpyrrolidone-40 (PVP-40), ovalbumin (OV) and Tween 20 in place of BSA
      as a blotting agent was useful in these glycosaminoglycan dependent reactions to
      minimize background due to non-specific interactions.

PMID- 17006644
TI  - UDP-Gal: GlcNAc-R beta1,4-galactosyltransferase--a target enzyme for drug design.
      Acceptor specificity and inhibition of the enzyme.
AB  - Galactosyltransferases are important enzymes for the extension of the glycan
      chains of glycoproteins and glycolipids, and play critical roles in cell surface
      functions and in the immune system. In this work, the acceptor specificity and
      several inhibitors of bovine beta1,4-Gal-transferase T1 (beta4GalT, EC 2.4.1.90)
      were studied. Series of analogs of N-acetylglucosamine (GlcNAc) and GlcNAc
      carrying glycopeptides were synthesized as acceptor substrates. Modifications
      were made at the 3-, 4- and 6-positions of the sugar ring of the acceptor, in the
      nature of the glycosidic linkage, in the aglycone moiety and in the 2-acetamido
      group. The acceptor specificity studies showed that the 4-hydroxyl group of the
      sugar ring was essential for beta4GalT activity, but that the 3-hydroxyl could be
      replaced by an electronegative group. Compounds having the anomeric beta
      configuration were more active than those having the alpha-configuration, and O-,
      S- and C-glycosyl compounds were all active as substrates. The aglycone was a
      major determinant for the rate of Gal-transfer. Derivatives containing a 2
      naphthyl aglycone were inactive as substrates although quinolinyl groups
      supported activity. Several compounds having a bicyclic structure as the aglycone
      were found to bind to the enzyme and inhibited the transfer of Gal to control
      substrates. The best small hydrophobic GlcNAc-analog inhibitor was found to be 1
      thio-N-butyrylGlcNbeta-(2-naphthyl) with a K(i) of 0.01 mM. These studies help to
      delineate beta4GalT-substrate interactions and will aid in the development of
      biologically applicable inhibitors of the enzyme.

PMID- 17006645
TI  - Comparative characterisation of recombinant invertebrate and vertebrate peptide O
      Xylosyltransferases.
AB  - Chondroitin and heparan sulphates have key functions in animal development and
      their synthesis is initiated by the action of UDP-alpha-D-xylose:proteoglycan
      core protein beta-D-xylosyltransferase (EC 2.4.2.26). cDNAs encoding this enzyme
      have been previously cloned from mammalian species; this in turn facilitated
      identification of corresponding Caenorhabditis elegans (sqv-6) and Drosophila
      melanogaster (oxt) genes. In the present study, we report the expression in
      Pichia pastoris and subsequent assay using either MALDI-TOF MS or RP-HPLC of
      recombinant forms of the Caenorhabditis xylosyltransferase SQV-6 and the human
      xylosyltransferase I, in addition to extending our previous studies on the
      xylosyltransferase from Drosophila. The enzyme activities were tested with a
      number of peptide substrates based on portions of the human bikunin, human
      perlecan and Drosophila syndecan core peptides. Whereas a variant of the latter,
      containing two Ser-Gly motifs was only modified on one of these motifs, the
      perlecan peptide with three Ser-Gly motifs could be multiply modified in vitro.
      Using this substrate, we could for the first time follow, by mass spectrometry,
      the xylosylation of a peptide with multiple xylosyltransferase acceptor motifs.

PMID- 17006647
TI  - A chemical synthesis of UDP-LacNAc and its regioisomer for finding
      'oligosaccharide transferases'.
AB  - A chemical synthesis of uridine 5'-diphospho-N-acetyllactosamine (Galbeta(1-
      >4)GlcNAc-UDP; UDP-LacNAc) and Galbeta(1-->3)GlcNAc-UDP is described. Coupling of
      the disaccharide imidate derivatives with dibenzylphosphate gave the
      corresponding 1-phosphates, which were condensed with UMP-imidazolate to give the
      target UDP-oligosaccharides after purification by anion exchange HPLC and gel
      filtration column chromatography. Using this methodology a variety of
      oligosaccharide nucleotide analogues can be synthesized. These UDP
      oligosaccharides may be useful for finding so-called ;oligosaccharide
      transferases', the glycosyltransferases which transfer the oligosaccharide moiety
      onto glycosyl acceptors.

PMID- 17006646
TI  - Isolation and characterization of heparan sulfate from various murine tissues.
AB  - Heparan sulfate (HS), is a proteoglycan (PG) found both in the extracellular
      matrix and on cell surface. It may represent one of the most biologically
      important glycoconjugates, playing an essential role in a variety of different
      events at molecular level. The publication of the mouse genome, and the intensive
      investigations aimed at understanding the proteome it encodes, has motivated us
      to initiate studies in mouse glycomics focused on HS. The current study is aimed
      at determining the quantitative and qualitative organ distribution of HS in mice.
      HS from brain, eyes, heart, lung, liver, kidney, spleen, intestine and skin was
      purified from 6-8 week old male and female mice. The recovered yield of HS from
      these organs is compared with the recovered whole body yield of HS. Structural
      characterization of the resulting HS relied on disaccharide analysis and (1)H-NMR
      spectroscopy. Different organs revealed a characteristic HS structure. These data
      begin to provide a structural understanding of the role of HS in cell-cell
      interactions, cell signaling and sub-cellular protein trafficking as well as a
      fundamental understanding of certain aspects of protein-carbohydrate
      interactions.

PMID- 17006648
TI  - Expressions of polypeptide: N-acetylgalactosaminyltransferase in leukemia cell
      lines during 1,25-dihydroxyvitamin D3 induced differentiation.
AB  - The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3] on two leukemia cell
      lines, K562 and SHI-1, and its relation to the expression of different subtypes
      of polypeptide: N-acetylgalactosaminyltransferase (pp-GalNAc-T) was studied. With
      morphological and cell flow-cytometric method, it was found that 1,25(OH)(2)D3
      induced the differentiation of both leukemia cell lines toward monocytic lineage,
      but not affected the cell growth and apoptosis. The expressions of different
      subtypes of pp-GalNAc-T, the initial glycosyltransferase in O-glycan synthesis,
      were studied with RT-PCR before and after the treatment of different
      concentrations of 1,25(OH)(2)D3. Among fourteen subtypes of pp-GalNAc-T (T1
      approximately T14), K562 cells obviously expressed pp-GalNAc-T2, T4, T5, T7 (T2
      was the highest) and SHI-1 cells apparently expressed pp-GalNAcT1, T2, T3 and T4
      (T4 was the highest) only. After K562 cells were treated 1, 25(OH)(2)D3 for 72 h,
      pp-GalNAc-T2, T4, T5, T7 were increased in a dose dependent manner. In contrast,
      pp-GalNAc-T1 and T2, especially T1, were up-regulated in SHI-1 cells by
      1,25(OH)(2)D3, but T3 was unchanged and T4 was down-regulated. The different
      alterations of pp-GalNAc-Ts in these two cell lines were probably related to the
      different structural changes of O-glycans during 1,25(OH)(2)D3 induced
      differentiation.

PMID- 17006649
TI  - Presence of natural anti-Galalpha1-4GalNAcbeta1-3Gal (anti-NOR) antibodies in
      animal sera.
AB  - Rare polyagglutinable NOR erythrocytes contain unusual globoside extention
      products terminating with a Galalpha1-4GalNAcbeta1-3Gal- unit. This trisaccharide
      epitope is recognized by recently characterized antibodies naturally occurring in
      most human sera (Duk et al., Glycobiology, 15, 109, 2005). These antibodies
      represent two major types of fine specificity. All these antibodies are most
      strongly inhibited by Galalpha1-4GalNAcbeta1-3Gal (NOR-tri), and weakly by
      Galalpha1-4Gal. However, the type 1 antibodies are strongly inhibited by
      Galalpha1-4Galbeta1-3Gal-R and weakly by Galalpha1-4GalNAc, while the type 2
      antibodies show the opposite reactivities with these two oligosaccharides.
      Similar antibodies have now been found in horse, rabbit and pig sera. The
      antibodies were purified from animal sera by affinity chromatography on Galalpha1
      4GalNAcbeta1-3Gal-human serum albumin(HSA)-Sepharose 4B conjugate. The
      specificity of the antibodies was determined by binding to ELISA plates coated
      with several alpha-galactosylated oligosaccharide-polyacrylamide (PAA) or -HSA
      conjugates and by inhibition with synthetic oligosaccharides. The purified
      antibodies bound specifically to conjugates containing NOR-tri. The inhibition of
      binding showed that the animal sera also contain two types of anti-NOR
      antibodies: type 2 was found in the horse serum, and a mixture of both types was
      present in rabbit and pig serum. These results indicate that anti-NOR, a new and
      distinct kind of anti-alphaGal antibody, are present in animal sera and show
      similar specificties and diversity as their counterparts found in human sera.

PMID- 17006650
TI  - Isolation and characterization of the potential receptor for wheat germ
      agglutinin from human neutrophils.
AB  - Neutrophils participate in host protection and central to this process is the
      regulation of oxidative mechanisms. We purified by affinity chromatography the
      receptor for the GlcNAc-specific WGA from CD14+ CD16+ cell lysates (WGAr). The
      receptor is a 141 kDa glycoprotein constituted by two subunits of 78 and 63 kDa.
      It is mainly composed of Ser, Asx, and Gly, and, in a minor proportion, His, Cys,
      and Pro. Its glycan portion contains GlcNAc, Gal, and Man; NeuAc and GalNAc were
      identified in a minor proportion. The amino acid sequence of the WGA receptor was
      predicted from tryptic peptides by MALDI-TOF, both subunits showed homology with
      cytokeratin type II (26 and 29% for the 78 and 63 kDa subunits, respectively);
      the 78 kDa subunit showed also homology with the human transferrin receptor
      (24%). Antibodies against WGAr induce higher oxidative burst than WGA, determined
      by NBT reduction; however, this effect was inhibited (p < 0.05) with GlcNAc
      suggesting that WGAr participates as mediator in signal transduction in
      neutrophils.

PMID- 17006652
TI  - Polysaccharide-based polymer blends: methods of their production.
AB  - The existing methods of preparing polymer blends of cellulose, chitin and
      chitosan with natural and synthetic polymers and their applications are reviewed.
      The methods of solid-phase blending of these polymers under conditions of joint
      action of high pressure and shear deformation are discussed. Normally, under
      these conditions the processes of dispersion of polymer particles, amorphization,
      mixing at different levels, depolymerization as well as a chemical interaction
      resulting in formation of branched and crosslinked structures can take place. The
      probability and intensity of these processes depend in many respects on the type
      and magnitude of the external force, but the properties of the polymers are of
      higher importance. The advantages of the method of joint action of high pressure
      and shear deformation compared to the conventional techniques of polysaccharides
      mixtures production are shown.

PMID- 17006651
TI  - Structural characterization of the N-glycans of gpMuc from Mucuna pruriens seeds.
AB  - Mucuna pruriens seeds are used in some countries as a human prophylactic oral
      anti-snake remedy. Aqueous extracts of M. pruriens seeds possess in vivo activity
      against cobra and viper venoms, and protect mice against Echis carinatus venom.
      It was recently demonstrated that the seed immunogen generating the antibody that
      cross-reacts with the venom proteins is a multiform glycoprotein (gpMuc), and the
      immunogenic properties of gpMuc seemed to mainly reside in its glycan chains. In
      the present study, gpMuc was found to contain only N-glycans. Part of the N
      glycans could be released with peptide-(N (4)-(N-acetyl-beta 
      glucosaminyl)asparagine amidase F (PNGase F-sensitive N-glycans); the PNGase F
      resistant N-glycans were PNGase A-sensitive. The oligosaccharides released were
      analyzed by a combination of MALDI-TOF mass spectrometry, HPLC profiling of 2
      aminobenzamide-labelled derivatives and (1)H NMR spectroscopy. The PNGase F
      sensitive N-glycans comprised a mixture of oligomannose-type structures ranging
      from Man(5)GlcNAc(2) to Man(9)GlcNAc(2), and two xylosylated structures,
      Xyl(1)Man(3)GlcNAc(2) and Xyl(1)Man(4)GlcNAc(2). The PNGase A-sensitive N
      glycans, containing (alpha 1-3)-linked fucose, were identified as
      Fuc(1)Xyl(1)Man(2)GlcNAc(2) and Fuc(1)Xyl(1)Man(3)GlcNAc(2). In view of the
      determined N-glycan ensemble, the immunoreactivity of gpMuc was ascribed to the
      presence of core (beta 1-2)-linked xylose- and core alpha (1-3)-linked fucose
      modified N-glycan chains.

PMID- 17006653
TI  - [Sleep in neurodegenerative disorders].
AB  - Neurodegenerative disorders are a group of heterogeneous, progressive disorders
      of varying etiology that affect one or more systems. They occur predominantly at
      older age, during which the structure and amount of sleep undergo changes.
      Neurodegenerative processes cause structural changes of the sleep/wake generators
      in the brainstem which result in disorders such as daytime sleepiness, insomnia,
      sleep-related movement and breathing disturbances, and disorders of the circadian
      rhythms. Some sleep disorders manifest years before the onset of
      neurodegenerative disorders and may serve as predictors. Polysomnography shows
      sleep fragmentation, tonic or phasic movements of the extremities, alteration of
      respiratory muscles, reduced slow wave sleep, REM sleep absence or without muscle
      atonia, increased arousal or wake activity, epileptiform EEG activity, and
      changes in sleep-related breathing. Very frequently, REM sleep behaviour disorder
      is associated with neurodegenerative disorders. In this overview we present
      symptoms, pathophysiology, and polysomnographic findings of sleep disorders in
      prevalent neurodegenerative disorders.

PMID- 17006654
TI  - Aneurysm of the ductus arteriosus in a patient with Larsen syndrome.
AB  - Larsen syndrome is characterized by multiple congenital joint dislocations and a
      characteristic flattened facial appearance. The aetiology is unknown, but the
      syndrome is considered a probable connective tissue disorder and the
      cardiovascular manifestations are similar to those of Marfan syndrome. We
      describe an 8-year-old girl with the characteristic features of Larsen syndrome
      who was also affected by a saccular aneurysm of the descending aorta, just distal
      to the left subclavian artery. We present the radiological findings and review
      the literature.

PMID- 17006655
TI  - Three-dimensional morphological magnetic resonance imaging in infants and
      children with congenital heart disease.
AB  - BACKGROUND: Cardiac MRI has become a clinically useful supplement to ECHO and
      conventional X-ray angiography in the diagnostic work-up of patients with
      congenital heart disease (CHD). Three-dimensional (3D) sequences are capable of
      depicting both intracardiac and extracardiac structures with high accuracy in
      adults and adolescents. However, diagnostic image quality in infants and young
      children has not yet been reported. OBJECTIVE: To apply an optimized 3D steady
      state free-precession (SSFP) MR sequence in infants and children with CHD.
      MATERIALS AND METHODS: In 20 patients (median age 1.8 years; ten male) with CHD,
      whole-chest imaging was performed with navigator-gated, isotropic 3D SSFP MRI at
      1.5 T. Sequence parameters were adapted to special requirements in infancy.
      Measurements of intra- and extracardiac structures were performed by two
      independent observers and compared to spin-echo and cine gradient-recalled-echo
      sequences. RESULTS: Diagnostic image quality was achieved with the 3D SSFP
      technique in all patients, allowing the establishment of a diagnosis in all
      cases. Interobserver comparison of measurements from reformatted 3D SSFP datasets
      revealed only minor differences with standard deviations ranging from 0.3-1.3 mm
      for intracardiac and 0.3-0.7 mm for extracardiac anatomy (P = ns). CONCLUSION:
      Isotropic 3D SSFP MRI allows reliable and accurate assessment of CHD, even in
      free-breathing infants and young children.

PMID- 17006656
TI  - Fos immunoreactivity in some locomotor neural centres of 6OHDA-lesioned rats.
AB  - In this study, we explore Fos expression (a measure of cell activity) in three
      nuclei associated with locomotion, namely the zona incerta, pedunculopontine
      tegmental nucleus and cuneiform nucleus (the latter two form the mesencephalic
      locomotor region) in hemiparkinsonian rats. Sprague-Dawley rats had small volumes
      of either saline (control) or 6 hydroxydopamine (6OHDA) injected into the medial
      forebrain bundle, the major tract carrying dopaminergic nigrostriatal axons.
      After various post-lesion survival periods, ranging from 2 h to 28 days, rats
      were perfused with formaldehyde and their brains processed for routine tyrosine
      hydroxylase and Fos immunocytochemistry. Our results showed a significant
      increase (P < 0.05) in the number of strongly labelled Fos+ cells in the
      cuneiform nucleus in the 6OHDA-lesioned cases compared to the controls after 7
      and 28 days survival periods. By contrast, there were no significant differences
      (P > 0.05) in the number of strong-labelled Fos+ cells in the zona incerta and
      pedunculopontine nucleus of 6OHDA-lesioned rats compared to controls at any
      survival period. Many of the Fos+ cells within the pedunculopontine and cuneiform
      nuclei were glutamatergic (35-60%), while none or very few were nitric oxide
      synthase+. In conclusion, we reveal an increase in the number of strongly
      labelled Fos+ cells within the cuneiform nucleus of the so-called defensive
      locomotive system in 6OHDA-lesioned rats. In relation to Parkinson disease, we
      suggest that this increase is associated with the akinesia or lack of movement
      seen in patients.

PMID- 17006657
TI  - Somite compartments in anamniotes.
AB  - Somites are a common feature of the phylotypic stage of embryos of all higher
      chordates. In amniote species like mouse and chick, somite development has been
      the subject of intense research over many decades, giving insight into the
      morphological and molecular processes leading to somite compartmentalization and
      subsequent differentiation. In anamniotes, somite development is much less
      understood. Except for recent data from zebrafish, and morphological studies in
      Xenopus, very little is known about the formation of somite compartments and the
      differentiation of somite derivatives in anamniotes. Here, we give a brief
      overview on the development of myotome, sclerotome and dermomyotome in various
      anamniote organisms, and point out the different mechanisms of somite development
      between anamniotes and the established amniote model systems.

PMID- 17006658
TI  - Regulation of scapula development.
AB  - The scapula is a component of the shoulder girdle. Its structure has changed
      greatly during evolution. For example, in humans it is a large quite flat
      triangular bone whereas in chicks it is a long blade like structure. In this
      review we describe the mechanisms that control the formation of the scapula. To
      assimilate our understanding regarding the development of the scapula blade we
      start by addressing the issue concerning the origin of the scapula. Experiments
      using somite extirpation, chick-quail cell marking system and genetic cell
      labelling techniques in a variety of species have suggested that the scapula had
      its origin in the somites. For example we have shown in the chick that the
      scapula blade originates from the somite, while the cranial part, which
      articulates with the upper limb, is derived from the somatopleure of the forelimb
      field. In the second and third part of the review we discuss the compartmental
      origin of this bone and the signalling molecules that control the scapula
      development. It is very interesting that the scapula blade originates from the
      dorsal compartment, dermomyotome, which has been previously been associated as a
      source of muscle and dermis, but not of cartilage. Thus, the development of the
      scapula blade can be considered a case of dermomyotomal chondrogenesis. Our
      results show that the dermomyotomal chondrogenesis differ from the sclerotomal
      chondrogenesis. Firstly, the scapula precursors are located in the hypaxial
      domain of the dermomyotome, from which the hypaxial muscles are derived. The fate
      of the scapula precursors, like the hypaxial muscle, is controlled by ectoderm
      derived signals and BMPs from the lateral plate mesoderm. Ectoderm ablation and
      inhibition of BMP activity interfers the scapula-specific Pax1 expression and
      scapula blade formation. However, only somite cells in the cervicothoracic
      transition region appear to be committed to form scapula. This indicates that the
      intrinsic segment specific information determines the scapula forming competence
      of the somite cells. Taken together, we conclude that the scapula forming cells
      located within the hypaxial somitic domain require BMP signals derived from the
      somatopleure and as yet unidentified signals from ectoderm for activation of
      their coded intrinsic segment specific chondrogenic programme. In the last part
      we discuss the new data that provides evidence that neural crest contributes for
      the development of the scapula.

PMID- 17006659
TI  - Size and number of binucleate and mononucleate superior cervical ganglion neurons
      in young capybaras.
AB  - The total number of neurons in the superior cervical ganglion (SCG) of adult
      capybaras is known from a previous study, where a marked occurrence of binucleate
      neurons (13%) was also noted. Here, distribution, number and fate of binucleate
      neurons were examined in younger, developing capybaras, aged 3 months. The mean
      neuronal cross-sectional area was 575.2 microm2 for mononucleate neurons and
      806.8 microm2 in binucleate neurons. Frequency of binucleate neurons was about
      36%. The mean ganglion volume was about 190 mm3 in young capybaras and the mean
      neuronal density was about 9,517 neurons/mm3. The total number of neurons per
      ganglion was about 1.81 mill. Neuronal cell bodies constituted 22.5% of the
      ganglion volume and the average neuronal volume was 23,600 microm3. By comparing
      the present data with those previously published the conclusion is drawn that the
      maturation period was characterized by the following points: a 26% remarkable
      decrease in neuronal density which was significant (P < 0.05) and a significant
      16% (P < 0.05) decrease in the total number of SCG neurons accompanied by a 23%
      decrease in the total number of SCG binucleate neurons.

PMID- 17006660
TI  - Glenoid defect associated with anterior shoulder instability: results of open
      Bankart repair.
AB  - The purpose of the study was to analyse the clinical results of an open Bankart
      repair for anterior instability in patients with a glenoid defect and those
      without a glenoid defect, and to identify factors related to the glenoid defect
      associated with anterior instability. The prospective study involved 20 patients
      with a glenoid defect (glenoid defect group) and 20 patients without a glenoid
      defect (control group) who were enrolled after an open Bankart repair. The
      average age of each group at the time of surgery was 28 and 23 years
      respectively. The average follow-up periods were 48 and 55 months. There were no
      significant differences in subjective pain and stability between the two groups.
      But the final Rowe score decreased significantly as the size of the glenoid
      defect increased. Redislocation or subluxation was seen in three patients in the
      glenoid defect group. The open Bankart procedure restored stability and improved
      shoulder functions in the patients with a glenoid defect associated with anterior
      instability, even though the glenoid defect group experienced a significant loss
      in the range of external rotation with the arm at the side, and the final outcome
      of the surgery depended upon the size of a glenoid defect. This was a
      therapeutic, level III case-control study.

PMID- 17006661
TI  - Is tennis elbow the same type of tendinosis as achilles and patellar tendinosis?

PMID- 17006662
TI  - Posterior instability near extension is related to clinical disability in
      isolated posterior cruciate ligament deficient patients.
AB  - The purpose of this study is to evaluate the relationship between the magnitude
      of knee laxity and posterior instability at different knee flexion angles and
      clinical disability in isolated posterior cruciate ligament (PCL) deficient
      patients. Knee laxity at 20 degrees and 70 degrees of knee flexion were evaluated
      using KT-2000 arthrometer, and the posterior instability at 20 degrees , 45
      degrees and 90 degrees of flexion were evaluated using stress radiography. We
      assessed the differences in the knee laxity and the tibial translation between
      isolated PCL deficient knees and normal knees, and between the patients with
      giving-way during activities of daily living (ADL) and without giving-way. There
      were statistical differences in the knee laxity and the tibial translation at all
      knee flexion angles between the PCL deficient knees and normal knees. The
      magnitude of the knee laxity at 20 degrees of flexion measured with KT-2000
      arthrometer was significantly larger in the patients with giving-way than those
      in the patients without giving-way although there was no significant difference
      in the tibial translation at 70 degrees between the two groups. The tibial
      translation in both medial and lateral compartments at 20 degrees and 45 degrees
      measured with stress radiography were significantly larger in the patients with
      giving-way than those in the patients without giving-way although there was not
      significant difference at 90 degrees between the two groups. These results
      suggested that the magnitude of the knee laxity and the posterior tibial
      translation at shallow knee flexion angles would be related to giving-way during
      ADL in isolated PCL deficient patients.

PMID- 17006663
TI  - Quadriceps femoris muscle voluntary isometric force production and relaxation
      characteristics before and 6 months after unilateral total knee arthroplasty in
      women.
AB  - The purpose of the present prospective intervention study was to evaluate
      voluntary isometric force production, relaxation and activation capacity of the
      quadriceps femoris (QF) muscle before and 6 months after unilateral total knee
      arthroplasty (TKA). TKA was performed in ten women with primary knee
      osteoarthritis (OA) using the condylar endoprostheses. Isometric maximal
      voluntary contraction (MVC) force, rate of force development at 50% of MVC
      (RFD50) and their ratio to body mass, half-relaxation time (HRT) and voluntary
      activation (VA) of the QF muscle were recorded in patients for operated and non
      operated leg before and 6 months after TKA. Established characteristics were
      compared with data on the dominant leg of ten age- and gender-matched controls.
      The clinical examination was performed using the Knee Society System (KSS) scores
      and pain intensity was assessed by visual analogue scale. MVC force in operated
      leg was lower (P < 0.05) before and 6 months after TKA as compared with the non
      operated leg (31 and 32%, respectively) and controls (48 and 44%, respectively).
      Patients had lower (P < 0.05) VA of the QF muscle in operated leg 6 months after
      TKA as compared to controls. Significant increase (P < 0.05) of KSS clinical
      scores and the tendency for the increasing of explosive force production of QF
      muscle in the operated leg were observed 6 months after TKA (RFD50 was 60% lower
      before TKA and 40% lower 6 months after surgery as compared to controls). When
      compared with the preoperative value, HRT prolongation (P < 0.05) was noted 6
      months after TKA in QF muscle of both legs in patients. Therefore, the present
      study confirmed that patients with knee OA had reduced force generation ability
      of QF muscle before TKA and the improvement of explosive force was noted 6 months
      after surgery.

PMID- 17006664
TI  - A 4D-microscopic analysis of the germ band in the isopod crustacean Porcellio
      scaber (Malacostraca, Peracarida)-developmental and phylogenetic implications.
AB  - Malacostracan crustaceans have evolved a conserved stereotyped cell division
      pattern in the post-naupliar germ band. This cleavage pattern is unique in
      arthropods investigated so far, and allows a combined analysis of gene expression
      and cell lineage during segmentation and organ development at the level of
      individual cells. To investigate the cell lineage in the germ band of the isopod
      Porcellio scaber, we used a 4D-microscopy system, which enables us to analyse
      every cell event in the living embryo. The study was combined with the analysis
      of the expression of the gene engrailed (en) at different stages of germ band
      formation. Our findings confirm the results of earlier investigations of the cell
      division pattern in the posterior part of the isopod germ band. Furthermore, we
      can show that in the anterior region, in contrast to the posterior part, cleavage
      directions are variable and cell sorting takes place-similar to other arthropod
      germ bands. Additionally, the gene expression pattern of en in this region is not
      as regular as in the post-naupliar germ band, and only later becomes regulated
      into its characteristic stripe pattern. The comparison of the cell lineage of P.
      scaber with that of other malacostracan crustaceans shows an enhancement in the
      velocity of cell divisions relative to the arrangement of these cells in rows in
      the isopod germ band. The striking similarity of the formation of the
      genealogical units in the anterior part suggests a sister group relationship
      between the peracarid taxa Tanaidacea and Isopoda.

PMID- 17006665
TI  - Evolutionary relationships of vertebrate NACHT domain-containing proteins.
AB  - Phylogenetic analyses of conserved [neuronal apoptosis inhibitory protein (NAIP),
      MHC class II transcription activator (CIITA), incompatibility locus protein from
      Podospora anserina (HET-E), and telomerase-associated protein (TP1)] (NACHT)
      domains were used to reconstruct the evolutionary history of vertebrate NACHT
      containing proteins. The results supported the hypothesis that NOD3 is basal to
      the other NACHT-containing proteins found in tetrapods. The latter formed two
      strongly supported clusters or subfamilies, here designated NALP and nucleotide
      binding oligomerization domain (NOD). The presence of apparent bony fish
      orthologs of NOD3 and CIITA supported the hypothesis that the origin of these
      molecules predates the origin of tetrapods, and the presence of avian sequences
      in both NALP and NOD clusters supported the origin of these subfamilies before
      the bird-mammal divergence. However, the extensive diversification of the NALP
      subfamily seen in mammals evidently occurred within the mammalian lineage. Both
      NALP and NOD subfamilies include members with differential expression in the
      antigen-presenting cells of the immune system, and the phylogenetic analyses
      supported the hypothesis that this expression pattern has evolved independently
      more than once in each of these subfamilies.

PMID- 17006666
TI  - Sustained activation of the mammalian target of rapamycin nutrient sensing
      pathway is associated with hepatic insulin resistance, but not with steatosis, in
      mice.
AB  - AIMS/HYPOTHESIS: Activation of nutrient sensing through mammalian target of
      rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We
      examined activation of mTOR-signalling in relation to insulin resistance and
      hepatic steatosis in mice. MATERIALS AND METHODS: Chronic hepatic steatosis and
      hepatic insulin resistance were induced by high-fat feeding of male C57BL/6Jico
      mice for 6 weeks. In addition, acute hepatic steatosis in the absence of insulin
      resistance was induced by pharmacological blockade of beta-oxidation using
      tetradecylglycidic acid (TDGA). mTOR signalling was examined in liver
      homogenates. RESULTS: High-fat feeding caused obesity (p<0.001), hepatic
      steatosis (p<0.05) and hepatic insulin resistance (p<0.05). The phosphorylation
      of mTOR and its downstream targets p70S6 kinase and S6 ribosomal protein was two
      fold higher in mice on a high-fat diet than in mice fed standard chow (all
      p<0.05) and associated with enhanced rates of protein synthesis. Acute induction
      of hepatic steatosis with TDGA had no effect on mTOR activity. The increased
      activity of the mTOR pathway in livers from mice on a high-fat diet could not be
      ascribed to diet-induced alterations in known modulators of mTOR activity such as
      circulating plasma leucine levels, phosphorylation of protein kinase B and AMP
      activated protein kinase, and changes in mitochondrial function.
      CONCLUSIONS/INTERPRETATION: High-fat diet induces increase of the mTOR nutrient
      sensing pathway in association with hepatic insulin resistance, but not with
      hepatic lipid accumulation as such.

PMID- 17006667
TI  - Not all imatinib resistance in CML are BCR-ABL kinase domain mutations.
AB  - Point mutations within the ABL kinase domain of the BCR-ABL gene are associated
      with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML).
      To obtain more information about the association between BCR-ABL mutations and
      type of imatinib resistance, we studied 30 early chronic phase (CP) CML patients,
      commencing imatinib therapy, using a conventional sequencing technique. Seven
      patients treated in late CP and three patients treated in the accelerated phase
      were included for comparison. Blood samples were collected before and every third
      month during imatinib therapy. Mutations were not seen in any blood sample
      collected before start of therapy. During imatinib treatment, 2 of the 30 early
      CP patients acquired point mutations and both of them had other signs of imatinib
      resistance. None of the five early CP patients with a complete hematologic
      response (HR), but no cytogenetic response at 12 months, displayed any missense
      mutation. Likewise, none of 12 early CP patients with detectable BCR-ABL
      transcripts but in complete hematologic and cytogenetic remission at 12 months
      displayed any mutation. We conclude that screening early CP patients for BCR-ABL
      mutations before start of imatinib therapy is not cost-effective. BCR-ABL kinase
      domain mutations do not appear to explain cytogenetic or molecular (detectable
      BCR-ABL transcripts by polymerase chain reaction) disease persistence in patients
      otherwise in stable disease. However, in patients with signs of expanding disease
      burden, a search for BCR-ABL mutations is warranted.

PMID- 17006668
TI  - Laser microdissection and cryogenic nuclear magnetic resonance spectroscopy: an
      alliance for cell type-specific metabolite profiling.
AB  - Laser microdissection was used as a tool to harvest secretory cavities (SC) from
      leaves of Dilatris pillansii Barker (Haemodoraceae) and from leaves and flowers
      of herbarium specimens of Dilatris corymbosa Berg. and Dilatris viscosa L.
      Cryogenic (1)H NMR spectroscopy and HPLC analysis of microdissected samples
      indicated specific accumulation of methoxyphenylphenalenones in the SC. The
      structures of two novel and a known natural product in the secretory tissue were
      confirmed by comparison with authentic compounds isolated from rhizomes and roots
      from which further phenylphenalenones and phenylphenalenone glucosides were
      isolated and identified by spectroscopic methods. How it will be possible to use
      the LMD technique to localize natural products in specific plant cell populations
      is also discussed.

PMID- 17006669
TI  - A comparative analysis of the Arabidopsis mutant amp1-1 and a novel weak amp1
      allele reveals new functions of the AMP1 protein.
AB  - Ethylene and gibberellins have a synergistic stimulatory effect on hypocotyl
      elongation of light-grown Arabidopsis thaliana (L.) Heynh. seedlings. A screen
      for mutants with decreased response to these hormones led to the isolation of a
      novel allele (ampl-7) of the ALTERED MERISTEM PROGRAM (AMP) 1 locus. The amp1-7
      allele contains a missense mutation causing a phenotype, which is weaker than
      that of the amp1-1 mutant that carries a nonsense mutation. The mutant phenotype
      prompted the hypothesis that AMP1 is involved in ethylene and GA signalling
      pathways or in a parallel pathway-controlling cell and hypocotyl elongation and
      cellular organization. Amp1 mutants contain higher zeatin concentrations causing
      enlargement of the apical meristem, which was confirmed by cytokinin application
      to wild type seedlings. Light grown amp1 seedlings have shorter hypocotyls than
      wild type; however, application of cytokinins promotes hypocotyl elongation of
      both Col-0 and amp1. We suggest that in amp1 mutants either zeatin overproduction
      or its action is strictly localized.

PMID- 17006670
TI  - Identification of a regulatory SNP in the retinol binding protein 4 gene
      associated with type 2 diabetes in Mongolia.
AB  - Increased levels of retinol binding protein 4 (RBP4) in serum is associated with
      insulin resistance. To examine this further, the genomic region of RBP4 was
      genetically surveyed in Mongolian people, who as a group are suffering from a
      recent rapid increase in diabetes. The RBP4 gene was screened by DHPLC system,
      and the PCR fragments which showed heteroduplex peaks in multiple samples were
      followed by direct sequencing to identify common polymorphisms in 48 Mongolian
      diabetic samples. Identified single nucleotide polymorphisms (SNPs) were
      genotyped in 511 control and 281 type 2 diabetes samples. The functions of SNPs
      in the regulatory region were assessed by reporter gene assay and electrophoretic
      mobility shift assay. Possible association between functional SNPs and serum RBP4
      levels or metabolic parameters was statistically assessed. Nine SNPs were
      identified in the RBP4 gene. A case-control study revealed that the rare alleles
      of four SNPs were associated with increased risk of diabetes, even after
      Bonferroni correction (-803, G > A, P = 0.0054; +5169, C > T, P = 0.0025; +6969,
      G > C, P = 0.0015; +7542, T > del, P = 0.0015). The -803 G > A SNP influenced the
      transcription efficiency in a hepatocarcinoma cell line as well as the binding
      efficiency of hepatocyte nuclear factor 1 alpha to the motif. In addition, the 
      803 A allele was associated with increased serum RBP4 levels in diabetic
      patients. We have identified a functional SNP in the RBP4 gene associated with
      type 2 diabetes in Mongolian people.

PMID- 17006671
TI  - Elevated male European and female African contributions to the genomes of African
      American individuals.
AB  - The differential relative contribution of males and females from Africa and
      Europe to individual African American genomes is relevant to mapping genes
      utilizing admixture analysis. The assessment of ancestral population
      contributions to the four types of genomic DNA (autosomes, X and Y chromosomes,
      and mitochondrial) with their differing modes of inheritance is most easily
      addressed in males. A thorough evaluation of 93 African American males for 2,018
      autosomal single nucleotide polymorphic (SNP) markers, 121 X chromosome SNPs, 10
      Y chromosome haplogroups specified by SNPs, and six haplogroup defining mtDNA
      SNPs is presented. A distinct lack of correlation observed between the X
      chromosome and the autosomal admixture fractions supports separate treatment of
      these chromosomes in admixture-based gene mapping applications. The European
      genetic contributions were highest (and African lowest) for the Y chromosome
      (28.46%), followed by the autosomes (19.99%), then the X chromosome (12.11%), and
      the mtDNA (8.51%). The relative order of admixture fractions in the genomic
      compartments validates previous studies that suggested sex-biased gene flow with
      elevated European male and African female contributions. There is a threefold
      higher European male contribution compared with European females (Y chromosome
      vs. mtDNA) to the genomes of African American individuals meaning that admixture
      based gene discovery will have the most power for the autosomes and will be more
      limited for X chromosome analysis.

PMID- 17006672
TI  - Evidence for statistical epistasis between catechol-O-methyltransferase (COMT)
      and polymorphisms in RGS4, G72 (DAOA), GRM3, and DISC1: influence on risk of
      schizophrenia.
AB  - Catechol-O-methyltransferase (COMT) regulates dopamine degradation and is located
      in a genomic region that is deleted in a syndrome associated with psychosis,
      making it a promising candidate gene for schizophrenia. COMT also has been shown
      to influence prefrontal cortex processing efficiency. Prefrontal processing
      dysfunction is a common finding in schizophrenia, and a background of inefficient
      processing may modulate the effect of other candidate genes. Using the NIMH
      sibling study (SS), a non-independent case-control set, and an independent German
      (G) case-control set, we performed conditional/unconditional logistic regression
      to test for epistasis between SNPs in COMT (rs2097603, Val158Met (rs4680),
      rs165599) and polymorphisms in other schizophrenia susceptibility genes. Evidence
      for interaction was evaluated using a likelihood ratio test (LRT) between nested
      models. SNPs in RGS4, G72, GRM3, and DISC1 showed evidence for significant
      statistical epistasis with COMT. A striking result was found in RGS4: three of
      five SNPs showed a significant increase in risk [LRT P-values: 90387 = 0.05 (SS);
      SNP4 = 0.02 (SS), 0.02 (G); SNP18 = 0.04 (SS), 0.008 (G)] in interaction with
      COMT; main effects for RGS4 SNPs were null. Significant results for SNP4 and
      SNP18 were also found in the German study. We were able to detect statistical
      interaction between COMT and polymorphisms in candidate genes for schizophrenia,
      many of which had no significant main effect. In addition, we were able to
      replicate other studies, including allelic directionality. The use of epistatic
      models may improve replication of psychiatric candidate gene studies.

PMID- 17006673
TI  - Subsets of SNPs define rare genotype classes that predict ischemic heart disease.
AB  - Single nucleotide polymorphisms (SNPs) are hypothesized to explain the genetic
      predisposition to ischemic heart disease (IHD) in the general population. Lack of
      evidence for a role of such variation is fostering pessimism about the utility of
      genetic information in the practice of medicine. In this study we determined the
      utility of exonic and 5' SNPs in apolipoprotein E (APOE) and lipoprotein lipase
      (LPL) when considered singly and in combination for predicting incidence of IHD
      in 8,456 individuals from the general population during 24 years of follow-up. In
      men, LPL D9N improved prediction of IHD (P = 0.03) beyond smoking, diabetes and
      hypertension. The group of men heterozygous and homozygous for the rare D9N
      variant had a hazard ratio (HR) of 1.69 (95% confidence interval = 1.10-2.58)
      relative to the most common genotype. Pairwise combinations of D9N with -219G > T
      in APOE and N291S and S447X in LPL significantly improved the prediction of IHD
      (P = 0.05 in women, P = 0.04 in men, P = 0.03 in men, respectively) beyond
      smoking, diabetes and hypertension, and identified subgroups of individuals (n =
      6-94) with highly significant HRs of 1.92-4.35. These results were validated in a
      case-control study (n = 8,806). In conclusion, we present evidence that
      combinations of SNPs in APOE and LPL identify subgroups of individuals at
      substantially increased risk of IHD beyond that associated with smoking, diabetes
      and hypertension.

PMID- 17006674
TI  - [Foreign body-induced angiosarcoma 60 years after a shell splinter injury].
AB  - An 84-year-old gentleman developed an angiosarcoma in the lateral temporal fossa
      60 years after a World War II injury. The tumour resection confirmed the close
      spatial relationship of the tumour and a shell splinter. Analysis of the metallic
      composition showed no clear carcinogenic potential of the ingredients; an
      inflammation-related carcinogenesis seems more probable. A review of the
      literature revealed two similar cases.

PMID- 17006675
TI  - Interindividual variability of aminoglycoside pharmacokinetics in preterm
      neonates at birth.

PMID- 17006676
TI  - Reversible immobilization of proteins with streptavidin affinity tags on a
      surface plasmon resonance biosensor chip.
AB  - Dissociation of biotin from streptavidin is very difficult due to their high
      binding affinity. The re-use of streptavidin-modified surfaces is therefore
      almost impossible, making devices containing them (e.g. surface plasmon resonance
      (SPR) sensor chips) expensive. This paper describes a new protocol for reversible
      and site-directed immobilization of proteins with streptavidin affinity tags on
      the streptavidin-coated SPR biosensor chip (SA chip). Two streptavidin affinity
      tags, nano-tag and streptavidin-binding peptide (SBP tag), were applied. They
      both can specifically interact with streptavidin but have weaker binding force
      compared to the biotin-streptavidin system, thus allowing association and
      dissociation under controlled conditions. The SA chip surface could be
      regenerated repeatedly without loss of activity by injection of 50 mM NaOH
      solution. The fusion construct of a SBP tag and a single-chain antibody to mature
      bovine prion protein (scFv-Z186-SBP) interacts with the SA chip, resulting in a
      single-chain-antibody-modified surface. The chip showed kinetic response to the
      prion antigen with equilibrium dissociation constant K (D) approximately equal to
      4.01 x 10(-7). All results indicated that the capture activity of the SA chip has
      no irreversible loss after repeated immobilization and regeneration cycles. The
      method should be of great benefit to various biosensors, biochips and immunoassay
      applications based on the streptavidin capture surface.

PMID- 17006677
TI  - Development of a monoclonal antibody-based enzyme-linked immunosorbent assay for
      the analysis of glycyrrhizic acid.
AB  - Glycyrrhizic acid (GL) is a major active compound of licorice. The specific
      monoclonal antibody (MAb) (designated as 8F8A8H42H7) against GL was produced with
      the immunogen GL-BSA conjugate. The dissociation constant (Kd) value of the MAb
      was approximately 9.96x10(-10) M. The cross reactivity of the MAb with
      glycyrrhetic acid was approximately 2.6%. The conventional indirect competitive
      enzyme-linked immunosorbent assay (icELISA) and simplified icELISA adapted with a
      modified procedure were established using the MAb. The IC50 value and the detect
      range by the conventional icELISA were 1.1 ng mL-1 and 0.2-5.1 ng mL-1,
      respectively. The IC50 value and the detect range by the simplified icELISA were
      5.3 ng mL-1 and 1.2-23.8 ng mL-1, respectively. The two icELISA formats were used
      to analyze GL contents in the roots of wild licorice and different parts of
      cultivated licorice (Glycyrrhiza uralensis Fisch). The results obtained with the
      two icELISAs agreed well with those of the HPLC analysis. The correlation
      coefficient was more than 0.98 between HPLC and the two icELISAs. The two
      icELISAs were shown to be appropriate, simple, and effective for the quality
      control of raw licorice root materials.

PMID- 17006678
TI  - Revising the quantitative analysis laboratory: what to keep? What to change?

PMID- 17006679
TI  - Influence of different purification techniques on triamcinolone yield and
      particle size spectrum.
AB  - BACKGROUND: To systematically investigate the common purification techniques for
      commercially available triamcinolone acetonide preparations and the influence of
      different filter parameters on final yield, reproducibility and particle size
      spectrum. METHODS: Two non-filter techniques using either sedimentation or
      centrifugation, and two different filter techniques were tested. Filters with
      different characteristics were investigated with the pore size ranging from 0.1
      to 5.0 microm, and the filter diameter ranging from 4 to 30 mm. Only sterile
      standard syringe filters with low adsorptive characteristics (hydrophilic
      cellulose filter membranes) for pharmaceutical use were employed. For
      quantification, triamcinolone acetonide was dissolved in 60% methanol and
      measured spectrophotometrically at 239 nm. The crystal size spectrum was
      determined using a particle size analyzer that combines electronic pulse area
      analysis and resistance measurement. RESULTS: Depending on the purification
      technique used the resulting triamcinolone doses differed significantly. While
      the centrifugation method achieved purification without relevant loss, the
      sedimentation method yielded only 28.7% compared to the original commercial
      suspension, and in addition, the predictability was low (range 8.1-17.2 mg). With
      filter techniques high and consistent doses with a good reproducibility were
      achieved, but results were highly dependent on the filter characteristics. The
      final triamcinolone amount inversely correlated with the filter diameter due to a
      uniform loss of crystalline particles. In contrast, enlarging the pore size
      caused a substantial shift in the particle size spectrum due to a selective loss
      of small crystalline particles. CONCLUSIONS: The most common purification
      techniques vary notably in regard to final triamcinolone doses, reproducibility
      and particle size spectrum. The appropriate choice of the filter parameters seems
      to be more important than assumed, as pore size and filter diameter substantially
      influence both the final TA doses and the particle size of the TA crystals.

PMID- 17006680
TI  - Real-time imaging of transscleral diode laser cyclophotocoagulation by optical
      coherence tomography.
AB  - PURPOSE: To present optical coherence tomography (OCT) for real-time imaging of
      cyclophotocoagulation effects. METHODS: In a pilot study, real-time transscleral
      OCT images were generated during diode laser cyclophotocoagulation in four eyes
      of four patients suffering from uncontrolled glaucoma using a specially designed
      contact applicator containing the OCT fiber, a focussing fiber optic and the
      fiber of the diode laser. RESULTS: When the contact system was used, two layers
      could be differentiated: a superficial thick hyperreflective complex representing
      conjunctiva, Tenon's capsule, episclera and sclera, and a thinner hyporeflective
      layer representing the ciliary body. During cyclophotocoagulation, real-time OCT
      showed a clear and sudden thickening of the ciliary body in the treated area.
      CONCLUSION: This new OCT device represents a first step towards visual, real-time
      imaging of cyclophotocoagulation. After further adaptation of the delivery
      system, further trials are needed to correlate OCT findings with aqueous
      production and intraocular pressure.

PMID- 17006681
TI  - Intravitreal bevacizumab therapy for neovascular age-related macular
      degeneration: a pilot study.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab therapy
      for neovascular age-related macular degeneration (ARMD). METHODS: Patients with
      diagnosis of neovascular ARMD without any other ocular pathology were injected
      with 2.5 mg of intravitreal bevacizumab. A complete ophthalmic examination was
      undertaken in all patients, including best corrected visual acuity (BCVA), slit
      lamp biomicroscopy and ocular fundus examination. Ophthalmic follow-up
      evaluations included visual acuity measurements, optical coherence tomography
      (OCT) imaging, and fluorescein angiography at first, second and fourth week post
      injection. RESULTS: 39 eyes of 39 patients were injected. The median age was 76
      years-old (range 65-90), median visual acuity was 1.18 logMAR (range 0.18-3.00)
      and median retinal thickness was 388 microns (range 157-1237). By the fourth week
      of treatment, the median visual acuity was 0.88 (range 0.18-2.78) and median
      retinal thickness was 247 microns (range 108-1262). Statistically significant
      differences were found in visual acuity and retinal thickness before and after
      intravitreal injection (p=0.002, p<0.001, Wilcoxon rank test). CONCLUSIONS: Our
      results suggest that intravitreal bevacizumab is well tolerated and is associated
      with improvement in BCVA and decreased mean retinal thickness by OCT. Further
      controlled and long term evaluation of intravitreal bevacizumab for the treatment
      of neovascular ARMD is warranted.

PMID- 17006682
TI  - Desensitization of cold- and menthol-sensitive rat dorsal root ganglion neurones
      by inflammatory mediators.
AB  - The interaction between cold sensitivity and inflammation in mammals is not
      entirely understood. We have used adult rat dorsal root ganglion neurones in
      primary culture together with calcium microfluorimetry to assess the effects of
      selected inflammatory mediators on cold responses of cold- and menthol-sensitive
      (most likely TRPM8-expressing) neurones. We observed a high degree of functional
      co-expression of TRPM8, the receptors for the inflammatory agents bradykinin,
      prostaglandin E2 and histamine, and TRPA1 in cultured sensory neurones. Treatment
      with either bradykinin or prostaglandin E2 led to a reduction in the amplitude of
      the response to cooling and shifted the threshold temperature to colder values,
      and we provide evidence for a role of protein kinases C and A, respectively, in
      mediating these effects. In both cases the effects were mainly restricted to the
      subgroups of cold- and menthol-sensitive cells which had responded to the
      application of the inflammatory agents at basal temperature. This desensitization
      of cold-sensitive neurones may enhance inflammatory pain by removing the
      analgesic effects of gentle cooling.

PMID- 17006683
TI  - Dynamics of quadrupedal locomotion of monkeys: implications for central control.
AB  - We characterized the three-dimensional kinematics and dynamics of quadrupedal
      gait of young adult rhesus and cynomolgus monkeys while they walked with diagonal
      and lateral gaits at 0.4-1.0 m/s on a treadmill. Rigid bodies on the wrist,
      ankle, and back were monitored by an optical motion detection system (Optotrak).
      Kinematic data could be normalized using characteristic stride length, reducing
      variance due to different gait styles, to emphasize common characteristics of
      swing and stance parameters among animals. Mean swing phase durations fell as
      walking speed increased, but the swing phase durations increased at each walking
      velocity as a linear function of increases in amplitude, thereby following a main
      sequence relationship. The phase plane trajectories of the swing phases, i.e.,
      plots of the relation of the rising and falling limb velocity to limb position in
      the sagittal (X-Z) plane, had unique dynamic characteristics. Trajectories were
      separable at each walking velocity and increases in swing amplitude were linearly
      related to peak swing velocities, thus comprising main sequences. We infer that
      the swing phase dynamics are set by central neural mechanisms at the onset of the
      swing phases according to the intended amplitude, which in turn is based on the
      walking velocity in the stance phases. From the many dynamic similarities between
      swing phases and rapid eye movements, we further suggest that the swing phases
      may be generated by neural mechanisms similar to those that produce saccades and
      quick phases of nystagmus from a signal related to sensed or desired walking
      velocity.

PMID- 17006685
TI  - Controlling reaching movements with predictable and unpredictable target motion
      in 10-year-old children and adults.
AB  - We investigated interception behavior in adults and 10-year-old children.
      Participants had to intercept virtual targets moving on either a predictable
      (linear) or unpredictable (non-linear) path (with random direction changes).
      Targets moved at two different velocities, which varied randomly from trial to
      trial. Participants reached for the targets via a force-feedback device. Reaching
      movements for linearly moving targets in a block of linearly moving targets were
      compared with reaching movements for linearly moving targets in the context of
      non-linearly moving targets. Movement direction and maximum speed of the first
      sub-movement were analyzed as well as frequency of target hits and number of sub
      movements. Unpredictable target motion caused faster movement speeds than
      predictable target motion for both children and adults. Additionally,
      unpredictable target motion caused children and adults to gear their initial
      movement direction further towards the current position of the target, while with
      predictable target motion, they geared their initial movement direction further
      ahead of the target towards an anticipated interception position. Together, these
      results suggest differential processing of predictable and unpredictable object
      behavior in an interception task, and that this differential processing is
      already in place in 10-year-olds.

PMID- 17006684
TI  - Neuroprotective effects of safflor yellow B on brain ischemic injury.
AB  - The present study was conducted to investigate whether safflor yellow B (SYB) had
      a protective effect on cerebral ischemic injury and to determine the possible
      mechanisms in vivo and in vitro. In vivo, Male Wistar-Kyoto (WKY) rats were used
      to make the model of middle cerebral artery occlusion (MCAO). The behavioral test
      was used to measure neurological deficit scores for evaluation of the ischemic
      damage of brain. The infarction area of brain was assessed in brain slices
      stained with 2% solution of 2,3,5-triphenyl tetrazolium chloride (TTC).
      Spectrophotometric assay was used to determine the activities of superoxide
      dismutase (SOD) and glutathione peroxidase (GPx), contents of malondialdehyde
      (MDA) and adenosine triphosphate (ATP) of the brain. Furthermore, the respiratory
      control ratio (RCR = state 3/state 4) was assessed in the brain mitochondria. In
      vitro, the effect of SYB was tested in cultured fetal cortical cells exposed to
      glutamate to identify its neuroprotection against neurons damage. The results in
      vivo showed that SYB at doses of 3.0 and 6.0 mg kg(-1) markedly decreased the
      neurological deficit scores and the infarction area in MCAO rats. At the same
      time, SYB significantly improved mitochondrial energy metabolism, decreased MDA
      content, and increased SOD and GPx activities in ischemic brain. The results in
      vitro showed that SYB remarkably inhibited neuron damage induced by glutamate in
      cultured fetal cortical cells. These suggest that SYB might act as a potential
      neuroprotective agent against the cerebral ischemia-induced injury in rat brain
      through reducing lipid peroxides, scavenging free radicals, and improving the
      energy metabolism.

PMID- 17006686
TI  - Neuronal activity in monkey primary somatosensory cortex is related to
      expectation of somatosensory and visual go-cues.
AB  - The present study was to investigate whether neuronal activity in primary
      somatosensory cortical areas (SI) differs when monkeys expect go-cues of
      different sensory modalities. Two monkeys made wrist extensions and flexions
      after steadily holding wrist at a center position. Movements were guided by
      increases in vibration to the monkey's palm (VIB), visual targets (VIS), or both
      in combination (COM). Neuronal activity recorded in SI during the early and late
      phases (i.e., the first and last 250 ms) of the instructed delay periods (IDP)
      were analyzed. Of 406 neurons recorded during all three paradigms, 263 (64.8%)
      showed significant changes in firing rates (FR) between the early and late IDP
      phases during either VIB or VIS trials and were selected for further analyses.
      The selected neurons were classified as VIB- or VIS-biased, depending on the
      paradigm (VIB or VIS) in which the greater FR changes occurred. Both increases
      and decreases in FRs were observed during the analyzed epochs. Most VIB-biased
      neurons showed the biggest FR changes during VIB trials and the least during VIS
      trials. Conversely, most VIS-biased neurons had the biggest FR changes during VIS
      trials and the least during VIB trials. For both VIB- and VIS-biased neurons,
      however, the FR changes were intermediate during COM trials. These results
      suggest that SI neurons play an important role in initiating/executing wrist
      movements. Neurons involved in wrist movements showed biases to the modality of
      cueing signals. Most SI neurons were biased to only one sensory modality. The
      expectation-related FR changes suggest different involvement by SI in movement
      initiation when tasks are guided by vibratory and visual signals.

PMID- 17006688
TI  - Impaired scaling of responses to vestibular stimulation in incomplete SCI.
AB  - Patients with incomplete spinal cord injury (iSCI) have impaired postural control
      leading to a high danger of falling. Clinically, it is impossible to assess the
      extent to which postural instability due to sensorimotor deficit is influenced by
      a disturbance in the vestibulospinal pathways. Galvanic vestibular stimulation
      (GVS) was applied to investigate changes in the vestibular spinal responses and
      their potential influence on postural stability in iSCI patients. Six chronic
      iSCI patients and age-matched controls were stimulated with a bipolar binaural
      stimulus. The centre of pressure (CoP) and soleus EMG responses during free
      standing with closed eyes on firm and compliant ground were measured. The
      impairment in postural stability was assessed by the mean amplitude of CoP
      deflections during two minutes undisturbed standing. Although iSCI patients were
      significantly less stable than controls, direct GVS responses of the soleus EMG
      and postural sways tended to be increased on firm ground. The GVS responses
      increased when changing from firm to compliant ground, showing a close
      correlation between the extent of postural instability and the response
      amplitudes. Therefore, challenging proprioceptive feedback induced a significant
      up-modulation of the GVS responses. However, when we took the postural
      instability in iSCI patients into account, the EMG and CoP responses to GVS were
      reduced compared to controls. The combined assessment of EMG and CoP responses to
      GVS complements the clinical examination and permits evaluation of the
      preservation and modulation of vestibulospinal responses in iSCI.

PMID- 17006687
TI  - The role of medial prefrontal cortex in context-specific inhibition during
      reversal learning of a visual discrimination.
AB  - Rats with medial prefrontal cortex or sham lesions were trained on a visual
      discrimination task designed for the eight-arm radial maze. After reaching
      asymptotic performance on this task, both groups were divided into sub-groups
      that would experience reversal learning in the same or different context from
      original training. The results showed that both groups reversed in the different
      context had accelerated learning compared to the groups reversed in the same
      context. Reversal learning in rats with medial prefrontal cortex damage was
      faster than sham animals in the same context. These and other results from a
      transfer test suggest that the medial prefrontal cortex participates in the
      behavioral effects of a context-specific inhibitory association acquired during
      visual discrimination learning.

PMID- 17006689
TI  - Axo-somatic inhibition of projection neurons in the lateral nucleus of amygdala
      in human temporal lobe epilepsy: an ultrastructural study.
AB  - Here, we report ultrastructural alterations in the synaptic circuitry of the
      human amygdala related to neuronal cell densities in surgical specimens of
      patients suffering from temporal lobe epilepsy (TLE). The neuronal cell densities
      quantified in the basolateral complex of amygdala were significantly reduced only
      in the lateral nucleus (LA) of TLE patients as compared to autopsy or non-Ammon's
      horn sclerosis (AHS) controls (Nissl staining, immunostaining against the
      neuronal marker NeuN). For this reason, we focussed on the LA to perform a more
      detailed quantitative ultrastructural analysis, which revealed an inverse
      correlation between the number of axo-somatic inhibitory synaptic profiles at the
      somata of glutamic acid decarboxylase (GAD)-negative projection neurons and the
      extent of perisomatic fibrillary gliosis. In contrast, the density of GAD
      immunoreactive interneurons positively correlated with the number of axo-somatic
      inhibitory synaptic profiles. The fibrillary material in perisomatic glial cell
      processes was preferentially labeled by the astroglial marker S100B. In addition,
      a qualitative study of the dendrites of GAD- and parvalbumin (PARV)-containing
      interneurons showed that they were often contacted by asymmetrical excitatory
      synapses. Our results are in line with anatomical data from rodents and cats,
      which show that amygdalar interneurons form axo-somatic inhibitory synapses on
      GAD-negative projection neurons, whereas the interneurons themselves receive
      excitatory input from recurrent collaterals of projection neurons and from
      cortico- and thalamo-amygdalar afferents. The structural reorganization patterns
      observed in the GABAergic circuitry are compatible with a reduced feedback or
      feed forward inhibition of amygdalar projection neurons in human TLE.

PMID- 17006690
TI  - Neuromuscular-skeletal constraints on the acquisition of skill in a discrete
      torque production task.
AB  - The organisation of the human neuromuscular-skeletal system allows an extremely
      wide variety of actions to be performed, often with great dexterity. Adaptations
      associated with skill acquisition occur at all levels of the neuromuscular
      skeletal system although all neural adaptations are inevitably constrained by the
      organisation of the actuating apparatus (muscles and bones). We quantified the
      extent to which skill acquisition in an isometric task set is influenced by the
      mechanical properties of the muscles used to produce the required actions.
      Initial performance was greatly dependent upon the specific combination of
      torques required in each variant of the experimental task. Five consecutive days
      of practice improved the performance to a similar degree across eight actions
      despite differences in the torques required about the elbow and forearm. The
      proportional improvement in performance was also similar when the actions were
      performed at either 20 or 40% of participants' maximum voluntary torque capacity.
      The skill acquired during practice was successfully extrapolated to variants of
      the task requiring more torque than that required during practice. We conclude
      that while the extent to which skill can be acquired in isometric actions is
      independent of the specific combination of joint torques required for target
      acquisition, the nature of the kinetic adaptations leading to the performance
      improvement in isometric actions is influenced by the neural and mechanical
      properties of the actuating muscles.

PMID- 17006691
TI  - Grain characterization and milling behaviour of near-isogenic lines differing by
      hardness.
AB  - Wheat grain hardness is a major factor affecting the milling behaviour and end
      product quality although its exact structural and biochemical basis is still not
      understood. This study describes the development of new near-isogenic lines
      selected on hardness. Hard and soft sister lines were characterised by near
      infrared reflectance (NIR) and particle size index (PSI) hardness index, grain
      protein content, thousand kernel weight and vitreousness. The milling behaviour
      of these wheat lines was evaluated on an instrumented micromill which also
      measures the grinding energy and flour particle size distribution was
      investigated by laser diffraction. Endosperm mechanical properties were measured
      using compression tests. Results pointed out the respective effect of hardness
      and vitreousness on those characteristics. Hardness was shown to influence both
      the mode of fracture and the mechanical properties of the whole grain and
      endosperm. Thus, this parameter also acts on milling behaviour. On the other
      hand, vitreousness was found to mainly play a role on the energy required to
      break the grain. This study allows us to distinguish between consequences of
      hardness and vitreousness. Hardness is suggested to influence the adhesion forces
      between starch granules and protein matrix whereas vitreousness would rather be
      related to the endosperm microstructure.

PMID- 17006692
TI  - Unexpected and potentially misleading TTF-1 expression: a word of caution.

PMID- 17006693
TI  - Validation and application of the sentinel lymph node concept in malignant vulvar
      tumours.
AB  - PURPOSE: Inguinal lymphadenectomy, unilateral or bilateral, is widely used in
      cases of vulvar squamous cell carcinoma and melanoma but has a high morbidity.
      Sentinel lymph node (SLN) biopsy may be used in the management of these patients.
      The aims of this study were firstly to determine the reliability of SLN biopsy in
      predicting regional lymph node status and secondly to apply this technique in the
      routine clinical setting. METHODS: We prospectively studied 70 women with vulvar
      malignancies. The first 50 cases were of squamous vulvar cancer and were used to
      validate the SLN technique in this clinical setting (validation group). Once a
      satisfactory success rate had been achieved in the validation group, the SLN
      technique was applied to a further 20 patients with vulvar malignancies, i.e.
      squamous cell carcinoma (n=12) and melanomas (n=8) (application group). Dynamic
      and static images were acquired after the injection of 74-148 MBq of a colloidal
      albumin, and continued until SLN identification. Fifteen minutes before surgery,
      blue dye injection was administered in a similar manner to the radiocolloid.
      After incision, a hand-held gamma probe was used to find the SLN. In the
      validation group, dissection of the SLN was always followed by lymphadenectomy.
      In the application group, this procedure was only performed if the SLN was
      positive for metastases. For pathological staging, samples were evaluated using
      haematoxylin and eosin and immunohistochemistry. RESULTS: In the validation
      group, lymphoscintigraphy allowed SLN detection in 49/50 patients (98%). Blue dye
      detected the SLN in 40/50 patients (80%). In 16 patients (33%), the SLN showed
      metastases in the pathology study. All 33 patients with negative SLN had regional
      lymph nodes negative for metastases (negative predictive value 100%). In the
      application group, lymphoscintigraphy showed drainage to an SLN in 19 out of 20
      patients (95%) and blue dye demonstrated a stained SLN in 17/20 patients (85%).
      Seven of the 19 SLN-identified nodes (37%) were positive for metastases.
      CONCLUSION: SLN identification permits the accurate pathological study of
      regional nodes and could reduce the high morbidity of current surgical treatment
      in vulvar tumour patients if the technique were to be adopted on a routine
      clinical basis.

PMID- 17006694
TI  - Latex allergy in health care workers in Taiwan: prevalence, clinical features.
AB  - BACKGROUND: Latex allergy is becoming a major health concern among healthcare
      workers, of whom approximately 2.8 to 18% are reportedly sensitized. OBJECTIVE:
      The purpose of this study was to analyze the results of a natural rubber latex
      (NRL) allergy screening program to identify sensitized hospital employees.
      METHODS: Nurses (n = 130) assigned to operating theaters and intensive care units
      were evaluated using a written questionnaire for symptoms of atopy (asthma,
      rhinoconjunctivitis, and atopic eczyma), possible reactions to latex gloves,
      other medical devices and previous surgery. Serological testing for total
      immunoglobulin E (IgE), latex-specific IgE, and specific-IgE to melon, banana,
      kiwi, tomato, and chestnut were performed using Pharmacia CAP radioallergosorbent
      tests. Skin pick test (SPT) for latex allergen was also performed. RESULTS:
      Elevated serum total IgE was found in 22(16.9%) of the 130 nurses, 3(16.7%) of
      whom had increased latex-specific IgE further confirmed by SPT. The overall
      prevalence of latex allergy was 2.3% (3/130). No cross reactive fruit-allergy was
      found among the latex-sensitized nurses. CONCLUSION: This study supports the
      existence of other forms of atopy are related to an increased risk of latex
      sensitization. The NRL screening program used in this study is feasible for use
      in identifying latex-sensitized employees.

PMID- 17006695
TI  - Direct stimulatory effects of the TLR2/6 ligand bacterial lipopeptide MALP-2 on
      neutrophil granulocytes.
AB  - Bacterial lipopeptides represent a group of bacterial compounds able to trigger
      the functions of cells of the innate immune response. Whereas diacylated
      lipopeptides are recognized by TLR2/6 dimers, triacylated lipopeptides were shown
      to act via TLR2/1 dimers. Although several previous studies dealt with the effect
      of the TLR2/1 ligand Pam(3)CysSK(4) on neutrophil granulocytes (PMN), it is still
      not clear whether TLR2/6 ligand lipopeptides can directly influence PMN
      functions. In the present study we used highly purified human neutrophils to
      investigate the direct effects of the diacylated mycoplasmal macrophage
      activating lipopeptide-2 (MALP-2) on the function of neutrophil granulocytes.
      After exposure to 10 ng/ml MALP-2 neutrophils acquired activated cell shape,
      secreted IL-8 and MIP-1beta and their phagocytic capacity was enhanced. Analysis
      of cell surface activation markers confirmed the activating effect of MALP-2, the
      expression of CD62L was downregulated whereas CD11b was upregulated on PMN after
      exposure to MALP-2. The constitutive apoptosis of PMN was inhibited after
      exposure to MALP-2. However, MALP-2 exerted only a short-term effect on the
      apoptosis of resting neutrophils, a longer lasting effect was observed after
      transendothelial migration. MALP-2 did not directly induce the production of
      reactive oxygen intermediates but primed PMN for a fMLP-induced oxidative burst.
      The migration of neutrophils was enhanced after treatment with MALP-2. This was
      due, however, to a chemokinetic rather than to a chemotactic effect.
      Pam(3)CysSK(4) also activated PMN, but in comparison to MALP-2, at higher
      concentrations. These findings suggest that diacylated lipopeptides are important
      microbial structures recognized by and acting on neutrophil granulocytes.

PMID- 17006696
TI  - [What does "PSA recurrence mean? "Active surveillance" for all risk groups is an
      option].

PMID- 17006697
TI  - [Local recurrence of prostate cancer after curative therapy. HIFU (Ablatherm) as
      a treatment option].
AB  - In terms of effectivity and impact, no ideal approach is as yet available for
      treatment of local recurrence of prostate cancer. We direct our attention mainly
      toward high-intensity focused ultrasound (HIFU). HIFU therapy (Ablatherm) is only
      performed in our department when the following criteria are met: the recurrent
      tumor must be visualizable with imaging procedures (for HIFU, transrectal
      ultrasound is employed), the tumor must be accessible to the scanner head
      (penetration depth: 25 mm), and finally the diagnosis of recurrent tumor has to
      be histologically confirmed. An indisputable advantage of HIFU is the option of
      easily administering HIFU therapy for a second time in the presence of tumor
      remnants or in the event of cancer recurrence. Depending on the primary cancer
      treatment given, salvage HIFU achieves a biopsy-proven tumor-free state in 60-74%
      of patients. These results are in line with those that can be obtained with other
      salvage strategies (radical prostatectomy, radiation therapy). However HIFU shows
      reduced postoperative morbidity with less side effects.

PMID- 17006698
TI  - [PET and PET/CT in relapsing prostate carcinoma].
AB  - Of patients with carcinoma of the prostate undergoing therapeutic regimes with
      curative intent, 15-23% will ultimately relapse and 16-35% will need some sort of
      salvage therapy within 5 years. Of relapsing patients, 50% will have local
      recurrence and 50% systemic disease with or without local recurrence. Therefore,
      localization of recurrent prostate cancer is critical for selecting a local or
      systemic therapeutic strategy. Modern fusion imaging with PET/CT and 11C/18F
      choline or 11C-acetate has augmented the diagnostic imaging spectrum for
      assessment of relapsing prostate cancer. In 60-70% of patients with biochemical
      relapse, recurrent tumor can be detected and anatomically precisely localized.
      Detection sensitivity is probably negatively correlated with serum PSA
      concentration. Below a PSA level of 1 ng/ml, mean detection sensitivity is
      probably 50-66%. Fusion imaging with 11C-choline PET/CT and MRI possesses a high
      potential for early localization of recurrent prostate carcinoma.

PMID- 17006699
TI  - [Recurrence of prostate cancer--value of salvage radiotherapy].
AB  - Approximately 25% of patients experience recurrent disease after radical
      prostatectomy. Most frequently, the only evidence of a relapse is a rising PSA
      level without clinical evidence. Without further treatment the natural history of
      PSA progression results in local recurrence or distant metastasis of prostate
      cancer. Since a proportion of these biochemical failures relate to a local
      recurrence, radiotherapy offers a potential curative approach. Up to now, no
      randomized studies are available. Therefore any decision can only be based on
      prospective observation studies or retrospective data. The data available
      indicate that optimal results can be obtained in patients with PSA levels below 1
      2 ng/ml or even lower, a documented R1 resection, and a PSA doubling time>10
      months. Doses of 64-66 Gy seem to be required for adequate control. Side effects
      are generally well acceptable and importantly no adverse effects on urinary
      continence have been documented. Taken together, radiotherapy is the only
      treatment option with curative potential in situations where a local failure is
      highly likely.

PMID- 17006700
TI  - [PSA recurrence following radical prostatectomy and radiotherapy].
AB  - Relapses after curative therapy for localised prostate cancer using radiotherapy
      or radical prostatectomy occur in a significant percentage of cases, even in
      times of continually improving patient selection. The definition of a biochemical
      relapse after surgery is a PSA value of >or=0.4 ng/ml. After radiotherapy with
      maintenance of the organ and residual PSA production the definition is more
      complicated. The current algorithm is based on the ASTRO consensus of 1996 and
      defines a relapse as three consecutive increases in PSA above the post
      therapeutic low. A biochemical relapse can indicate a local relapse, systemic
      metastasising of the disease or a combination of both. The differentiation of
      these two possibilities can be made, apart from imaging modalities, primarily on
      the basis of variation in PSA kinetics, whereby a short PSA doubling time and
      early PSA increase after primary therapy indicate a systemic problem.

PMID- 17006701
TI  - [Introduction to the topic: organ manifestation of the underlying rheumatic
      disease and association with widespread diseases].

PMID- 17006702
TI  - Changes in the liver function tests during the attacks of familial Mediterranean
      fever.
AB  - The present study aims to investigate whether or not FMF patients display
      abnormal liver functions during attack periods. About 41 consecutive FMF patients
      with attacks were enrolled on this study. Bilirubin levels, liver transaminases,
      erythrocyte sedimentation rate and C-reactive protein (C-RP) levels were
      determined within the first 72 h after the onset of attacks. This procedure could
      be performed on only 28 of these 41 FMF patients, 4 weeks after the attack of the
      patients' had completely disappeared. As for the disease control group, 44
      patients were determined to be eligible for the study. Another 31 healthy
      individuals were also included. Hyperbilirubinemia was determined in 11 of the 41
      patients (26.8%) with FMF. The number of FMF patients with hyperbilirubinemia was
      significantly higher than in DC and HC (P < 0.001, P = 0.03, respectively).
      Levels of liver transaminases slightly increased in four patients with FMF during
      the attack and two of these four patients had also mild hyperbilirubinemia. A
      significant correlation was found between C-RP levels and total and unconjugated
      bilirubin levels in FMF patients with attack (r = 0.43, P = 0.01; r = 0.40, P =
      0.02, respectively). In conclusion, mild hyperbilirubinemia may occur in one
      fourth of the patients with FMF during the attack period.

PMID- 17006703
TI  - Hypertrophic pulmonary osteoarthropathy (HPOA) (Pierre Marie-Bamberger syndrome):
      two cases presenting as acute inflammatory arthritis. Description and review of
      the literature.
AB  - We report the cases of two middle-aged male smokers who presented to the early
      synovitis clinic with an acute phase response, synovitis of the wrists and ankles
      and clubbing of the fingers, but no respiratory symptoms. Both proved to have
      primary lung tumours with hypertrophic pulmonary osteoarthropathy, in one case
      resolving promptly with treatment of the carcinoma. We review the literature,
      including theories on pathogenesis.

PMID- 17006704
TI  - Does cyclically iloprost infusion prevent severe isolated pulmonary hypertension
      in systemic sclerosis? Preliminary results.
AB  - The objective of this study was to present our clinical experience about
      scleroderma-related pulmonary hypertension in the patients treated with
      intermittent iloprost infusions. Eighty-one patients affected by systemic
      sclerosis (12 men, 69 women; 30 with diffuse pattern and 51 with limited pattern;
      mean age 55.1 years; mean duration of disease 105.3 months) have been treated
      with cyclic iloprost infusions for at least 15 months (range 15-126 months).
      During the last 4 months all patients underwent Doppler echocardiography in order
      to estimate the value of systolic pulmonary artery pressure. In 14 subjects
      (17.2%) systolic pulmonary artery pressure was = or > 35 mmHg. Four patients
      presented high systolic pulmonary artery pressure associated with pulmonary
      fibrosis (mean value 40.5 +/- 4.5 mmHg). Ten women (one with diffuse pattern of
      disease and nine with limited form) showed isolated high systolic pulmonary
      artery pressure; one of these patients underwent right heart catheterization
      which resulted normal. The remaining nine patients (mean age of 67.1 years; age
      at the onset of scleroderma 52.2 years) showed estimated systolic pulmonary
      artery pressure values between 35 and 50 mmHg. Among these patients affected by
      isolated pulmonary hypertension only one has been receiving bosentan in
      association with iloprost infusions. None of our scleroderma patients treated
      with cyclic iloprost infusions developed severe isolated pulmonary hypertension.
      In systemic sclerosis the multiple effects of iloprost on endothelium, platelets
      and cytokine network may counteract the vasospastic profile of lung
      microvasculature in pulmonary arterial hypertension and the consequent vascular
      wall remodelling, thus preventing the development of severe illness.

PMID- 17006705
TI  - Immunogenicity, efficacy and adverse events of adalimumab in RA patients.
AB  - To assess the immunogenicity of adalimumab, a human anti-TNF-alpha mAb, we
      evaluated the formation of antibodies to adalimumab, efficacy and adverse events
      among 15 patients with highly active rheumatoid arthritis. Four patients were
      treated with adalimumab as monotherapy, and 11 patients with concomitant DMARDs.
      Disease activity was measured by DAS28. The antibodies were detected by ELISA.
      Thirteen (87%) patients withdrew from therapy within 45 weeks and overall 13
      (87%) patients showed antibodies to adalimumab including 11 patients who withdrew
      from therapy. In four patients without concomitant DMARDs and in nine patients
      with concomitant DMARDs, we detected anti-adalimumab antibodies. Overall, five of
      seven patients with adverse drug reactions and all nine patients with lack of
      efficacy were associated with the formation of antibodies. Two antibody-positive
      patients developed an exantheme. The results indicate that adalimumab is, in
      spite of its fully human sequences, immunogenic and induces antibodies in a high
      rate of adalimumab-treated patients.

PMID- 17006706
TI  - [Leiomyosarcoma of the inferior vena cava].
AB  - Leiomyosarcomas of the inferior vena cava are rare and the clinical symptoms
      unspecific. We report a case of leiomyosarcoma of the inferior vena cava in an 82
      year-old woman presenting with weight loss and abdominal pain. Following
      elaborate preoperative examinations, surgical resection was performed and the
      inferior vena cava was reconstructed. Clinical signs, diagnosis, therapy, and
      prognosis are discussed.

PMID- 17006707
TI  - Treatment of a leaking ACE conduit with Deflux injections.
AB  - Faecal leakage from the catheter conduit can be troublesome and reduces the
      convenience of use of antegrade continence enema (ACE). We report the results of
      Deflux injection treatment for leaking ACE conduits in nine patients. From 1994
      to the end of 2005, 81 patients underwent a procedure for ACE [appendicostomy
      with wrap (AW) n = 29, appendicostomy straight (AS) n = 44, Monti-Yang ileal tube
      (MY) n = 5, lateral caecal flap (LCF) n = 1, caecal tube (CT) n = 1, sigmoid tube
      (ST) n = 1]. Nine (11%) patients (AW n = 3, AS n = 1, MY n = 3, LCF n = 1, ST n =
      1) had persistent stomal leak and underwent Deflux injections of the ACE conduit.
      With the patients in general anaesthesia, the conduit was visualised with CH10.5
      cystoscope. At the junction of the conduit and colon, 0.5-1.0 ml of Deflux was
      injected submucosally at three sites to create intermingling mounds in order to
      narrow the conduit. After the injections, a balloon catheter was left in the
      conduit for 3-7 days. When necessary, the injections were repeated. The result
      was graded as no improvement, moderate improvement, significant improvement. Nine
      patients underwent a median of 2 (range 1-4) injections. No major complications
      occurred. The results after a median follow-up of 22 (range 3-53) months from the
      first injection were as follows: no improvement (n = 1), moderate improvement (n
      = 5), significant improvement (n = 3). Repeated injection of the ACE conduit with
      Deflux is a low invasive method and provides moderate to good results in the
      majority of the patients who suffer from faecal leakage from conduit.

PMID- 17006708
TI  - Postnatal development of the mucosal plexus in the porcine small and large
      intestine.
AB  - Knowledge regarding the foetal and postnatal development of the enteric nervous
      system is crucial for the understanding of congenital disorders. While lot of
      information exists regarding the myenteric and submucosal plexuses, the
      development of the mucosal plexus has not been previously studied. The mucosal
      innervation seems to play an important role in the local reflex activity of the
      gut. In this study, we examined the development of enteric mucosal innervation in
      the pig at various ages of life. Small and large bowel paraffin-embedded
      specimens were stained with PGP 9.5 and neurofilament protein in three piglets
      from six age groups (60 and 90 days gestation, newborn, 4 and 12 weeks old, and
      adult pigs). Small and large bowel demonstrated identical innervation patterns.
      Myenteric and submucosal plexuses were stained with PGP 9.5 at 60 days gestation.
      However, the mucosal staining was first noted clearly at the newborn period. By 4
      weeks, PGP 9.5 staining was noted in small amounts within the mucosa. Inner
      proprial and villous fibres were seen ahead in time to the subepithelial fibres.
      Both inner proprial and villous staining became quiet prominent by 12 weeks of
      age and remained unchanged into adulthood. However, the subepithelial fibres
      appear to increase in adulthood. This study demonstrates for the first time that
      enteric mucosal innervation first appears only at birth. The immaturity of the
      mucosa generated reflex activity, and secretory functions may have implication in
      the management of functional intestinal obstruction in the premature infant.

PMID- 17006709
TI  - Long-term results of bowel function after treatment for Hirschsprung's disease: a
      29-year review.
AB  - Although various surgical procedures have been described to treat Hirschsprung's
      disease (HD), few studies have evaluated the long-term results of these children.
      The purpose of this study was to assess the long-term clinical outcome and bowel
      function of patients with HD. The hospital records of 259 consecutive patients
      with a confirmed histological diagnosis of HD during 1975-2003 were examined.
      Data was assessed for age at presentation, sex, clinical presentation, associated
      anomalies, level of aganglionosis, surgical procedures, complications and bowel
      function. Follow up was carried out by personal/telephone interviews with
      patients or their parents. Of the 259 patients with HD, 200 were males (77.2%)
      and 59 females (22.8%). Intestinal obstruction was the presenting feature in 147
      patients (56.8%), intestinal perforation in 5 (1.9%), enterocolitis in 30 (11.6%)
      and constipation in 77 (29.7%). Thirty-nine patients (15.1%) had associated
      Down's syndrome. Two hundred and nine patients (80.7%) had rectosigmoid disease,
      31 (12%) had long segment disease and 19 (7.3%) had total colonic aganglionosis.
      Forty-three patients (16.6%) had preoperative enterocolitis. Primary colostomy
      was performed in 160 patients and a primary pull through in 90. Seven patients
      had a sphincteromyectomy for ultrashort HD. Two patients died prior to treatment.
      Various pull through procedures were performed in these patients. Postoperative
      complications included: pelvic abcess in 2, rectal stricture in 10, perianal
      excoriation in 7, anastomotic leak in 8, intestinal obstruction in 3, wound
      dehiscence in 1, stomal prolapse/stenosis in 5, rectovesical fistula in 2 and
      enterocolitis in 56. Five patients underwent a redo pull through and 46 required
      a post pull through sphincterectomy. At the time of follow-up, 27 were lost to
      follow-up, 9 died, 18 had permanent stomas and 4 were too young to assess bowel
      function. Of the remaining 194 patients, bowel function was normal in 132 (68%).
      Twenty patients (10.3%) had soiling and 42 (21.7%) had constipation requiring
      laxatives or enemas. There was no difference in bowel function in relation to
      type of pull through operation. Only 34% of patients with Down's syndrome had
      normal continence. The majority of patients with HD continue to have disturbances
      of bowel function for many years before attaining normal continence.

PMID- 17006710
TI  - No correlation between circulating ACE activity and VO2max or mechanical
      efficiency in women.
AB  - The insertion (I) variant of the angiotensin-1 converting enzyme (ACE) I/D
      genetic polymorphism is associated with lower circulating and tissue ACE
      activity. Some studies have also suggested associations of ACE I/D genotype with
      endurance phenotypes. This study assessed the relationships between circulating
      ACE activity, ACE I/D genotype, mechanical efficiency and the maximal rate of
      oxygen uptake in sedentary individuals. Sixty-two untrained women were tested for
      mechanical efficiency during submaximal cycle ergometry (delta and gross
      efficiencies during exercise between 40 and 80 W) and the maximal rate of oxygen
      uptake during incremental treadmill running. Respiratory variables were measured
      using indirect calorimetry. Venous blood was obtained for direct assay of
      circulating ACE activity, allowing for the assessment of correlations between two
      continuous variables, rather than a categorical analysis of endurance phenotype
      by genotype alone. ACE I/D genotype was also determined, and was strongly
      associated with circulating ACE activity (P < 0.0005). Neither circulating ACE
      activity (27.4 +/- 8.4 nM His-Leu-ml(-1)) nor ACE genotype showed a statistically
      significant association with any of the endurance phenotypes measured. The weak
      correlations observed included r = -0.122 (P = 0.229) for the relationship
      between delta efficiency (23.9 +/- 2.5%) and circulating ACE activity and r =
      0.134 (P > 0.6) for the relationship between maximal aerobic power (149.1 +/-
      22.9 ml kg(-2/3) min(-1)) and circulating ACE activity. The data do not support a
      role for systemic ACE activity in the regulation of endurance performance in
      sedentary individuals, extending this observation to a large female cohort.

PMID- 17006711
TI  - Effect of exercise on postprandial lipemia in men with hypertriglyceridemia.
AB  - We examined the effect of exercise on postprandial lipemia (PPL) and insulin
      resistance in individuals with metabolic syndrome. Subjects were 10
      hypertriglyceridemia (HTG) males with insulin resistance [age = 40.1 +/- 2.2
      years, body weight = 96.3 +/- 3.3 kg, fasting triglyceride (TG) = 263 +/- 25
      mg/dl, VO(2)max = 37 +/- 1.1 ml/kg/min, and Homeostatic Model Assessment (HOMA
      IR, an index of insulin resistance) = 3.05 +/- 0.40]. Each subject performed a
      control trial (Ctr, no exercise), and three exercise trials at 40% (40%T), 60%
      (60%T), and 70% (70%T) of their VO(2)max. The order of trials was randomized and
      there were 1-2 weeks wash-out period between the trials. All subjects had a fat
      meal in each trial. In the exercise trials, subjects jogged on a treadmill for 1
      h at a designated intensity 12 h prior to a fat-meal ingestion. Blood samples
      were taken at 0 h (before the meal), and 2, 4, 6, and 8 h after the meal. The
      plasma TG, area score under TG concentration curve for over an 8 h-period (TG
      AUC) after the meal, and HOMA-IR were analyzed. The TG AUC score in 40%T was 30%
      lower (P = 0.003), 60%T was 31% lower (P = 0.02), and 70%T was 39% lower (P =
      0.02) than Ctr. There were no significant differences in the TG AUC scores among
      the exercise trials (P > 0.05). The insulin concentrations in both 60 and 70%T
      were lower than Ctr (P < 0.01) which did not differ from 40%T. HOMA-IR in both
      60%T (P = 0.041) and 70%T (P = 0.002) were lower than Ctr, but not different from
      40%T (HOMA-IR: Ctr = 3.05 +/- 0.40, 40%T = 2.67 +/- 0.35, 60%T = 2.49 +/- 0.31,
      70%T = 2.21 +/- 0.27). The results suggest that for physically inactive
      individuals with metabolic syndrome, exercising at low to moderate intensity may
      be sufficient to attenuate PPL and increase insulin sensitivity, whereas higher
      intensity exercise may be needed to normalize blood glucose.

PMID- 17006712
TI  - Reliability of 31P-magnetic resonance spectroscopy during an exhaustive
      incremental exercise test in children.
AB  - This study examined the reliability of (31)P-magnetic resonance spectroscopy
      (MRS) to measure parameters of muscle metabolic function in children. On separate
      days, 14 children (7 boys and 7 girls) completed three knee-extensor incremental
      tests to exhaustion inside a whole-body scanner (1.5 T, Phillips). The dynamic
      changes in the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) and
      intracellular muscle pH were resolved every 30 s. Using plots of Pi/PCr and pH
      against power output (W), intracellular thresholds (ITs) for each variable were
      determined using both subjective and objective procedures. The IT(Pi/PCr) and
      IT(pH) were observed subjectively in 93 and 81% of their respective plots,
      whereas the objective method identified the IT(Pi/PCr) in 88% of the plots. The
      IT(pH) was undetectable using the objective method. End exercise (END)
      END(Pi/PCr), END(pH), IT(Pi/PCr) and IT(pH) were examined using typical error
      statistics expressed as a % coefficient of variation (CV) across all three
      exercise tests. The CVs for the power output at the subjectively determined
      IT(Pi/PCr) and IT(pH) were 10.6 and 10.3%, respectively. Objective identification
      of the IT(Pi/PCr) had a CV of 16.3%. CVs for END(pH) and END(Pi/PCr) were 0.9 and
      50.0%, respectively. MRS provides a valuable window into metabolic changes during
      exercise in children. During knee-extensor exercise to exhaustion, END(pH) and
      the subjectively determined IT(Pi/PCr) and IT(pH) demonstrate good reliability
      and thus stable measures for the future study of developmental metabolism.
      However, the objectively determined IT(Pi/PCr) and END(Pi/PCr) displayed poor
      reliability.

PMID- 17006713
TI  - Biomechanical muscle properties and angiotensin-converting enzyme gene
      polymorphism: a model-based study.
AB  - Previous studies reported an association of angiotensin-converting enzyme (ACE)
      I/D gene polymorphism with physical performance. The study was based on the
      hypothesis that certain individual biomechanical muscle properties could be
      associated with ACE genotype and that they could influence athletes' physical
      performance. Movement-independent individual biomechanical muscle properties of
      62 sports students were determined by applying a mathematical model to
      experimental data. Subjects exerted concentric and isometric contractions at a
      leg-press. The model was based on a Hill-type muscle model, a function describing
      the geometrical arrangement of human leg extensor muscles, and an exponential
      function describing muscle activation. Mouthwash samples were taken to determine
      the ACE genotypes. Several combinations of experimentally determined
      biomechanical properties served as input variables for a discriminant analysis.
      We were able to show that individual biomechanical muscle properties correlated
      with ACE I/D gene polymorphism. With a combination of certain individual muscle
      parameters based on a Hill-type muscle model, we were able to separate three
      individual ACE genotypes (II, ID, DD) in a significant way (P<0.03) and correctly
      classify 89% of the cases using a discriminant analysis. We conclude that local
      biomechanical muscle properties are influenced by ACE genotype.

PMID- 17006714
TI  - Maximal fat oxidation rates in endurance trained and untrained women.
AB  - The aim of the present study was to examine the differences in fat oxidation
      between endurance trained (ET) and untrained (UT) women. Eight ET and nine UT
      women performed a progressive cycle ergometer test until exhaustion. The rate of
      fat oxidation was similar at low work rates (<or=90 W) but was 80-200% higher in
      ET subjects at 120-180 W. When related to relative exercise intensity, the fat
      oxidation was similar in the low-intensity domain (<or=40% VO2max), but higher in
      the ET subjects both at moderate intensities (45-60% VO2max; +22% vs. UT) and at
      high intensities (65-80% VO2max; +35% vs. UT). There was no difference in the
      maximal fat oxidation rates between the trained and untrained women. The relative
      exercise intensity that elicited the highest rate of fat oxidation (Fatmax) was
      56+/-3% and 53+/-2% VO2max in ET and UT women, respectively (NS). In biopsies
      from m. vastus lateralis, the activity of the enzymes citrate synthase, beta
      hydroxy acyl CoA dehydrogenase (HAD), and hormone sensitive lipase was higher in
      the ET subjects. The HAD activity correlated significantly with fat oxidation at
      moderate and high intensities. We conclude that the ET women had a higher fat
      oxidation at moderate- and high-exercise intensities both at same relative and at
      absolute intensity compared with the UT women. The HAD activity and fat oxidation
      rates were highly correlated indicating that training-induced adaptation in
      muscle fat oxidative capacity is an important factor for enhanced fat oxidation.
      Interestingly, maximal fat oxidation occurred at the same exercise intensity.

PMID- 17006716
TI  - Associations among maternal soy intake, isoflavone levels in urine and blood
      samples, and maternal and umbilical hormone concentrations (Japan).
AB  - OBJECTIVES: In utero exposure to high levels of endogenous estrogens has been
      hypothesized to increase breast cancer risk in later life. A high intake of soy
      has been suggested to protect against breast cancer. We examined the hypothesis
      that maternal soy intake may be inversely associated with pregnancy hormone
      levels. METHODS: The concentrations of hormones (estradiol, estriol, and
      testosterone) and isoflavones (genistein, deidzein, and equol) were measured in
      the maternal urine and serum, and umbilical cord blood of 194 women during
      pregnancy and at delivery. Soy intake during pregnancy was assessed by 5-day diet
      records at approximately the 29th week of pregnancy. RESULTS: High correlations
      were observed for isoflavone levels between maternal samples and umbilical cord
      blood, indicating that isoflavone can be transferred from the maternal to the
      fetal compartment. None of the hormones measured in umbilical cord blood was
      significantly associated with any of the isoflavones measured. There were a few
      significant associations between maternal hormone levels and isoflavone measures
      during pregnancy, but their patterns of associations varied by gestational week
      and differed depending on whether isoflavone exposure was measured by diet
      records, urine or serum. CONCLUSION: Our data contain no strong evidence showing
      that soy intake affects hormone levels during pregnancy.

PMID- 17006715
TI  - Acute and chronic effects of ketamine upon human memory: a review.
AB  - INTRODUCTION: Ketamine is attracting increasing research interest not only
      because of its powerful amnestic effects but also as a putative model of
      schizophrenia and as a substance with an expanding following of recreational
      users. OBJECTIVE: This article reviews the existing literature on the effects of
      acute ketamine on the memory of healthy volunteers and of repeated doses of
      ketamine in recreational users. CURRENT TRENDS: Although there have been
      relatively few, often methodologically diverse, studies to date of the mnemonic
      effects of ketamine, there is an emerging consensus that an acute dose of the
      drug impairs the manipulation of information in working memory and produces
      decrements in the encoding of information into episodic memory. Preliminary
      evidence suggests that ketamine may differ from other classic amnestic drugs in
      impairing aspects of semantic memory. Acute-on-chronic effects in ketamine users
      generally mimic the pattern seen in controlled studies with healthy volunteers.
      However, chronic ketamine use may be associated with a more specific pattern of
      memory decrements and with episodic memory impairment, which might not abate
      following cessation of use. FUTURE TRENDS: An important aim of future research
      should be to detail the specificity of ketamine's amnestic effects on both a
      neuropharmacological and a cognitive level.

PMID- 17006717
TI  - Communication and colorectal cancer screening among the uninsured: data from the
      Health Information National Trends Survey (United States).
AB  - OBJECTIVE: Colorectal cancer screening allows for both prevention and early
      detection of the disease, with early detection often resulting in improved
      prognosis. Too few Americans over 50 are screened for colorectal cancer, but
      among certain subpopulations screening rates are particularly low for various
      reasons. We examined the role of communication factors and insurance, with a
      specific focus on the uninsured to examine disparities in colorectal cancer
      screening. METHODS: We used Health Information National Trends Survey data to
      examine: disparities in colorectal cancer screening, by calculating proportions
      of subpopulations screened; and the association between communication and
      screening among the uninsured, by performing chi-square tests and simple logistic
      regression to examine the potential factors associated with screening. RESULTS:
      The uninsured were 64% less likely to be screened than the insured. Provider
      recommendation was the only significant communication measure, with the uninsured
      lacking a recommendation 98.5% less likely to be screened than those with one.
      CONCLUSION: These data suggest expansion of programs of screening among the
      uninsured and more aggressive communication campaigns to promote the awareness
      and provider recommendation of screening as possible ways to increase screening
      and reduce mortality of colorectal cancer.

PMID- 17006718
TI  - Association between the presence of bacterial 16S RNA in prostate specimens taken
      during transurethral resection of prostate and subsequent risk of prostate cancer
      (Sweden).
AB  - OBJECTIVE: To study bacterial 16S RNA in archival prostate samples from 352
      patients with benign prostate hyperplasia (BPH) and evaluate whether the presence
      of bacterial DNA was different in those who later developed prostate cancer (n =
      171) and in the matched controls that did not progress to cancer (n = 181).
      METHODS: 16S DNA PCR followed by cloning and sequencing the positive samples.
      RESULTS: In 96/352 (27%) of the prostate tissue specimens 16S RNA were detected.
      Sequence analysis revealed Propionibacterium acnes as the predominant
      microorganism (23% of 16S RNA positive patients). The second most frequent
      isolate-Escherichia coli was found in 12 (12%) patients. The other isolates
      included Pseudomonas sp. (3 patients), Actinomyces sp. (2), Streptococcus mutans
      (1), Corynebacterium sp. (2), Nocardioides sp. (1), Rhodococcus sp. (1)
      Veillonella sp. (2). In P. acnes positive samples 62% exhibited severe
      histological inflammation versus 50% in the bacteria-negative group (p = 0.602).
      The presence of P. acnes in the prostate was associated with prostate cancer
      development (OR 2.17, 95% CI 0.77-6.95). CONCLUSIONS: This study has revealed P.
      acnes as the most common bacteria in the prostate in BPH. Further studies are
      needed to clarify its role in contributing to the development of prostatic
      inflammation and prostate cancer.

PMID- 17006719
TI  - Influence of alternative mammographic screening scenarios on breast cancer
      incidence predictions (Finland).
AB  - BACKGROUND: A population-based early detection programme for breast cancer has
      been in progress in Finland since 1987. Recently, detailed information about
      actual screening invitation schemes in 1987-2001 has become available in
      electronic form, which enables more specific modeling of breast cancer incidence.
      OBJECTIVES: To present a methodology for taking into account historical
      municipality-specific schemes of mass screening when constructing predictions for
      breast cancer incidence. To provide predictions for numbers of new cancer cases
      and incidence rates according to alternative future screening policies. METHODS:
      Observed municipality-specific screening invitation schemes in Finland during
      1987-2001 were linked together with breast cancer data. The incidence rate during
      the observation period was analyzed using Poisson regression, and this was done
      separately for localized and non-localized cancers. For modeling, the screening
      programme was divided into seven different components. Alternative screening
      scenarios for future mass-screening practices in Finland were created and an
      appropriate model for incidence prediction was defined. RESULTS AND CONCLUSION:
      Expanding the screening programme would increase the incidence of localized
      breast cancers; the biggest increase would be obtained by expanding from women
      aged 50-59 to 50-69. The impacts of changes in the screening practices on
      predictions for non-localized cancers would be minor.

PMID- 17006721
TI  - Oral contraceptive use and risk of breast carcinoma in situ (United States).
AB  - OBJECTIVE: Our study assesses the impact of oral contraceptive use on breast
      carcinoma in-situ (BCIS) risk. METHODS: We conducted a population based case
      control study of incident BCIS among black and white women ages 35-64 years
      residing in Los Angeles County. Case patients (n = 567) were newly diagnosed with
      BCIS and control participants (n = 614) were identified by random digit dialing
      between 1 March 1995 and 31 May 1998. All subjects were required to have had a
      mammogram in the 2 years before case diagnosis or control recruitment. Data were
      collected during in-person interviews. Multivariable logistic regression analyses
      provide estimates of odds ratios (ORs) and 95% confidence intervals (95% CIs).
      RESULTS: Oral contraceptive use was not associated with risk of BCIS (OR = 1.04,
      95% CI (0.76-1.42)). Risk did not increase with longer periods of use. No
      associations with BCIS risk were observed for oral contraceptive use before first
      term pregnancy, age at first oral contraceptive use, or for time since last use.
      Risk was not modified by estrogen dose, age, race, or parity. CONCLUSIONS: Our
      results are consistent with recent results on invasive breast cancer reported for
      the Women's Contraceptive and Reproductive Experiences Study and show no
      association between oral contraceptive use and risk of BCIS.

PMID- 17006720
TI  - Meeting the mammography screening needs of underserved women: the performance of
      the National Breast and Cervical Cancer Early Detection Program in 2002-2003
      (United States).
AB  - OBJECTIVE: To examine the extent to which the National Breast and Cervical Cancer
      Early Detection Program (Program) has helped to meet the mammography screening
      needs of underserved women. METHODS: Low-income, uninsured women aged 40-64 are
      eligible for free mammography screening through the Program. We used data from
      the U.S. Census Bureau to estimate the number of women eligible for services. We
      obtained the number of women receiving Program-funded mammograms from the
      Program. We then calculated the percentage of eligible women who received
      mammograms through the Program. RESULTS: In 2002-2003, of all U.S. women aged 40
      64, approximately 4 million (8.5%) had no health insurance and had a family
      income below 250% of the federal poverty level, meeting Program eligibility
      criteria. Of these women, 528,622 (13.2%) received a Program-funded mammogram.
      Rates varied substantially by race and ethnicity. The percentage of eligible
      women screened in each state ranged from about 2% to approximately 79%.
      CONCLUSIONS: Although the Program provided screening services to over a half
      million low-income, uninsured women for mammography, it served a small percentage
      of those eligible. Given that in 2003 more than 2.3 million uninsured, low
      income, women aged 40-64 did not receive recommended mammograms from either the
      Program or other sources, there remains a substantial need for services for this
      historically underserved population.

PMID- 17006722
TI  - A prospective study of fish, marine fatty acids, and bladder cancer risk among
      men and women (United States).
AB  - OBJECTIVE: To evaluate prospectively the association between intakes of fish,
      marine fatty acids, and bladder cancer risk in two ongoing cohorts, the Health
      Professionals Follow-up Study and the Nurses' Health Study. METHODS: During 16
      and 18 years of follow-up, 501 and 235 incident cases of bladder cancer were
      diagnosed among men and women, respectively. Cox proportional hazard models were
      used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI)
      between fish intake and bladder cancer risk adjusting for age, total caloric
      intake, pack-years of cigarette smoking, and current smoking. RESULTS: We
      observed no significant overall association between total fish intake and bladder
      cancer risk, even when we compared >/=1 servings of fish per day to fish intake
      </=1-3 servings per month. Among men, a statistically significant lower risk of
      bladder cancer was observed among men consuming fish or high marine fatty acid,
      after excluding the first 4 years of follow-up (MV RR = 0.60; 95% CI, 0.38-0.94,
      for >/=1 total fish servings per day compared to </=1-3 servings per month).
      CONCLUSIONS: Overall, these findings suggest that fish intake is not likely to be
      appreciably associated with the risk of bladder cancer.

PMID- 17006723
TI  - NAT2, meat consumption and colorectal cancer incidence: an ecological study among
      27 countries.
AB  - The polymorphic gene NAT2 is a major determinant of N-acetyltransferase activity
      and, thus, may be responsible for differences in one's ability to bioactivate
      heterocyclic amines, a class of procarcinogens in cooked meat. An unusually
      marked geographic variation in enzyme activity has been described for NAT2. The
      present study re-examines the international direct correlation reported for meat
      intake and colorectal cancer (CRC) incidence, and evaluates the potential
      modifying effects of NAT2 phenotype and other lifestyle factors on this
      correlation. Country-specific CRC incidence data, per capita consumption data for
      meat and other dietary factors, prevalence of the rapid/intermediate NAT2
      phenotype, and prevalence of smoking for 27 countries were used. Multiple linear
      regression models were fit and partial correlation coefficients (PCCs) were
      computed for men and women separately. Inclusion of the rapid/intermediate NAT2
      phenotype with meat consumption improved the fit of the regression model for CRC
      incidence in both sexes (males-R (2) = 0.78, compared to 0.70 for meat alone; p
      for difference in model fit-0.009; females-R (2) = 0.76 compared to 0.69 for meat
      alone; p = 0.02). Vegetable consumption (inversely and in both sexes) and fish
      consumption (directly and in men only) were also weakly correlated with CRC,
      whereas smoking prevalence and alcohol consumption had no effects on the models.
      The PCC between NAT2 and CRC incidence was 0.46 in males and 0.48 in females when
      meat consumption was included in the model, compared to 0.14 and 0.15,
      respectively, when it was not. These data suggest that, in combination with meat
      intake, some proportion of the international variability in CRC incidence may be
      attributable to genetic susceptibility to heterocyclic amines, as determined by
      NAT2 genotype.

PMID- 17006724
TI  - Genetic polymorphisms in anti-inflammatory cytokine signaling and the prevalence
      of gastric precancerous lesions in Venezuela.
AB  - OBJECTIVES: The aim of the study was to assess the effects of genetic
      polymorphisms in anti-inflammatory mediators, i.e., IL10, IL4 and IL4R on the
      prevalence of gastric precancerous lesions and their interactions with other
      environmental factors. METHODS: The study population consisted of 2,033
      Venezuelan subjects known to have extremely high Helicobacter Pylori (HP)
      infection rates. The odds ratios (OR) and 95% confidence intervals (CI)
      associated with these polymorphisms were estimated by multinominal logistic
      regression models for gastric precursor lesions. RESULTS: We found a 60% increase
      in risk of intestinal metaplasia (IM) and dysplasia combined (OR 1.62, 95% CI:
      1.10-2.38) among the carriers of the IL10-1082 low activity allele. This
      increased risk was more pronounced for dysplasia than for IM. On the other hand,
      homozygotes with the low activity allele of the A398G polymorphism in the IL4R
      gene had a modest increase in risk of atrophic gastritis (OR = 1.52, 95% CI: 1.05
      2.21), compared with homozygotes of the high activity allele. There were no
      statistically significant synergetic interactions between these polymorphisms and
      environmental risk factors (low fruit intake, high starchy vegetable intake and
      cigarette smoking) for these lesions. CONCLUSION: While the results of the
      present study suggest roles of genetic variability in these anti-inflammatory
      mediators in different stages of gastric carcinogenesis, there is high likelihood
      that they were chance findings due to multiple comparisons.

PMID- 17006725
TI  - Prostate cancer incidence and intake of fruits, vegetables and related
      micronutrients: the multiethnic cohort study* (United States).
AB  - OBJECTIVE: To describe the relationship between the intake of fruits, vegetables,
      and related vitamins and antioxidants, and the risk of prostate cancer in male
      participants in a large multiethnic cohort study. METHODS: Food and nutrient
      intakes in 1993-1996 were calculated from a detailed food frequency questionnaire
      (FFQ) designed to account for the food and nutrient intake of the ethnic groups
      represented in the study (82,486 African-American, Japanese-American, Native
      Hawaiian, Latino and White males included here). Follow-up for incident cancers
      utilized local SEER registries. Vital status was ascertained using state death
      files. Data on PSA utilization from a later questionnaire was also examined.
      RESULTS: A total of 3,922 incident cancer cases were ascertained during follow
      up. Modestly increased risks of prostate cancer were observed in relation to
      higher intakes of several food items including light green lettuce and dark leafy
      green vegetables. Notably, no significant protective associations of any foods
      were seen, including tomato intake; and intakes of two complex foods containing
      tomato sauce (pizza and Spanish rice) were associated with modest increases in
      risk. PSA test use was significantly and positively related to intake of some of
      these same items, implying a degree of disease detection-bias. Analysis of non
      localized and high grade disease (1,345 cases) showed no significant protective
      associations with overall fruits and vegetables intake, related micronutrients,
      or with intake of selected complex food items. CONCLUSIONS: We found no
      statistically significant evidence of a protective effect against prostate cancer
      of higher levels of intake of any of these foods, associated micronutrients or
      supplements. A possible explanation for the positive associations with risk of
      several of the foods normally considered to be healthy is detection bias, since
      "healthy" dietary intake was related to greater use of the PSA test.

PMID- 17006726
TI  - Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of
      French women.
AB  - OBJECTIVE: Adequate folate intake may be important for breast cancer prevention.
      Its protective effect may be influenced by factors associated with folate
      metabolism. We sought to evaluate folate intake in relation to breast cancer risk
      and examine whether the relation is affected by alcohol and intake of vitamin
      B(2) and B(12). METHODS: A prospective cohort analysis of folate intake was
      conducted among 62,739 postmenopausal women in the French E3N cohort who had
      completed a validated food frequency questionnaire in 1993. During nine years'
      follow-up, 1,812 cases of pathology-confirmed breast cancer were documented
      through follow-up questionnaires. Nutrients were categorized in quintiles and
      energy-adjusted using the regression-residual method. Cox model-derived relative
      risks (RRs) were adjusted for known breast cancer determinants. RESULTS: The
      multivariate RR for extreme quintiles of folate intake was 0.78 (95% CI: 0.67
      0.90; p-trend = 0.001) [Median intake for Q(1) = 296 microg/day and Q(5) = 522
      microg/day]. There was no evidence to support effect modification by alcohol or
      B(2) intake. The decreasing trend was most marked in women with higher folate and
      vitamin B(12 )intake. However, test for interaction was not statistically
      significant (p = 0.29). CONCLUSIONS: High folate intake was associated with
      decreased breast cancer risk. Vitamin B(12) intake may modify this association.

PMID- 17006727
TI  - The influence of sevoflurane on the bispectral index, regional cerebral oxygen
      saturation, and propofol concentration during propofol/N2O anesthesia.
AB  - OBJECTIVE: This study was undertaken to investigate the influence of sevoflurane
      on the bispectral index (BIS), regional cerebral oxygen saturation (rSO(2)), and
      serum propofol concentration during propofol/N(2)O anesthesia. This study tested
      the hypothesis that sevoflurane affect BIS values, rSO(2), and the
      pharmacokinetics of propofol during propofol/ N(2)O anesthesia. METHODS: General
      anesthesia was administered to 15 ASA I-II patients with a continuous infusion of
      propofol to maintain a BIS value of 45 +/- 5. After recording baseline values,
      patients were assigned to receive sevoflurane (2.0%, 20 min). BIS values, rSO(2)
      using near-infrared spectroscopy, and hemodynamic parameters were recorded for 60
      min. Cardiac output (CO) and stroke volume (SV) were evaluated using impedance
      cardiograph methods. Propofol concentration was determined using high-performance
      liquid chromatography. RESULTS: Sevoflurane (2.0%, 20 min) decreased the BIS
      score from 47.4 +/- 8.2 to 27.3 +/- 5.9 (P < 0.01, n = 15) without affecting
      rSO(2). Sevoflurane decreased systolic blood pressure from 112.1 +/- 14.0 mmHg to
      96.5 +/- 13.2 mmHg (P < 0.001, n = 15) without affecting heart rate. Both CO and
      SV were significantly decreased during sevoflurane application. Propofol
      concentration was increased from 2.71 +/- 0.51 microg/ml to 3.30 +/- 0.57
      microg/ml (P < 0.05) after sevoflurane application, and was returned to baseline
      after sevoflurane washout. CONCLUSIONS: We have shown that sevoflurane decreases
      BIS values during propofol/N(2)O anesthesia without affecting rSO(2) and that
      this change is accompanied by an increase in serum propofol concentration.
      Changes in propofol concentration may be due to, at least in part, hemodynamic
      changes such as decreased CO produced by sevoflurane.

PMID- 17006728
TI  - Illumination correction on MR images.
AB  - OBJECTIVE: An important artifact corrupting Magnetic Resonance Images is the rf
      inhomogeneity, also called bias artifact. This anomaly produces an abnormal
      illumination fluctuation on the image, due to variations of the device magnetic
      field. This artifact is particularly strong on images acquired with a device
      specialized on upper and lower limbs due to their coil configuration. A method
      based on homomorphic filtering aimed to suppress this artifact was proposed by
      Guillemaud. This filter has two faults: it doesn't provide an indication about
      the cutoff frequency (cf) and introduces another illumination artifact on the
      edges of the foreground. This work is an improvement to this method because it
      resolves both problems. METHODS: The experimental setup has been performed on
      knee images obtained by 5 volunteers and acquired through an Artoscan device
      using the following parameters: Spin Echo sequence, Repetition time: 980 ms, Echo
      time: 26 ms, Slice thickness: 4 mm, Flip Angle: 90 degrees . RESULTS: Two
      specialists in orthoptics evaluated the results of the proposed approach by
      examining the restored images and validating the results produced by the filter.
      A quantitative evaluation has been performed on a manually segmented restored
      image using the coefficient of variation (cv) measure. CONCLUSIONS: Following the
      specialists qualitative evaluation, the illuminance of upper and lower peripheral
      zones results to be enhanced; a loose of contrast can be noted only in few cases.
      The Bias image exhibits an artifact focused usually on the central part of the
      foreground. The quantitative evaluation based on cv shows that this index is
      lowered for all the segmented regions with respect to the original value. The
      method is automatic and doesn't require any hypothesis on the tissues. A manual
      version of the algorithm can be also implemented allowing the physician to choose
      the preferred cf. In this case the value selected by the method can be considered
      as a default value.

PMID- 17006729
TI  - Utility of cardiac MRI for diagnosis and post-treatment follow-up of lupus
      myocarditis.
AB  - Clinical myocardial involvement in systemic lupus erythematosus is rare. Lupus
      myocarditis is usually not detected until significant decrease in myocardial
      function becomes clinically evident. This case report describes MR imaging of
      lupus myocarditis that was used for diagnosis and follow up in a patient who
      declined cardiac biopsy. We also review the literature related to myocardial
      imaging by MRI.

PMID- 17006730
TI  - Adenosine myocardial contrast echo in intermediate severity coronary stenoses: a
      prospective two-center study.
AB  - BACKGROUND: We sought to evaluate the role of adenosine myocardial contrast
      echocardiography (MCE) for the determination of functional relevance of coronary
      stenoses with intermediate angiographic severity and compared the results to
      single photon imaging (SPECT). We hypothezised that sole assessment of myocardial
      blood volume changes during adenosine on MCE would indicate functional stensosis
      relevance when accompanied by increased myocardial oxygen consumption (MVO2).
      METHODS: Fifty-seven patients with >or=1 coronary stenosis underwent adenosine
      MCE (ultraharmonic imaging) and exercise SPECT. On MCE, myocardial blood volume
      was assessed and constant or increased myocardial opacification during adenosine
      coupled with increased MVO2 was defined as normal and decreased opacification as
      abnormal. RESULTS: Rate-pressure product significantly increased during adenosine
      in all patients due to reflex tachycardia following mild hypotension, indicative
      of increased MVO2. Concordance between MCE and SPECT for the detection of
      reversible myocardial perfusion defects was 89% (kappa = 0.83). Comparison of
      regions between rest and during adenosine as opposed to comparison to remote
      regions of the same stage was important for accurate assessment because
      concordance betweenn MCE and SPECT was less on separate assessment at rest (73%,
      kappa = 0.40) compared to stress (91%, kappa = 0.81, P < 0.05) mainly due to
      territories scored normal on SPECT and abnormal on MCE. CONCLUSIONS: Assessment
      of myocardial blood volume changes during adenosine using MCE can be used for the
      determination of the functional relevance of coronary stenoses of intermediate
      angiographic severity if MVO2 is increased during adenosine.

PMID- 17006731
TI  - Coronary artery stent fracture.
AB  - Coronary stent fracture is a rare but potentially serious complication of
      coronary artery stenting. In light of the non-specific presentation of stent
      fracture, it is also an easily missed complication. In order to ensure rapid
      recognition and treatment of this entity, physicians must be aware of its
      existence and its possibility under the right circumstances. We present the case
      of a 61-year-old Guyanese male who presented with unstable angina secondary to a
      stent fracture within two weeks of elective percutaneous coronary intervention
      (PCI) for in-stent restenosis.

PMID- 17006732
TI  - Apex techniques, old and new, hold the key to estimated left ventricular end
      diastolic and right ventricular systolic pressure.

PMID- 17006733
TI  - Minimal invasive treatment of vesicouterine fistula: a case report.
AB  - We report a case of vesicouterine fistula presenting after cesarean operation.
      The fistula was treated successfully by cystoscopic fulguration of the tract and
      hormonal amenorrhea. Although various surgical approaches to this problem have
      been described, to date there is no reports of treatment of this problem via
      cystoscopic fulguration and hormonal amenorrhea. The problem has been solved by
      hormonal amenorrhea and cystoscopic fulguration. We advocate this simple
      technique as a primary approach to proper case of vesicouterine fistulas.

PMID- 17006734
TI  - Assessment of the continence status and patients' satisfaction after retropubic
      radical prostatectomy: a questionnaire based study.
AB  - OBJECTIVE: The aim of this study was to assess the continence status and
      patients' satisfaction after retropubic radical prostatectomy by a self
      administered questionnaire composed of 12 questions. MATERIALS AND METHODS: In
      total, 143 patients who underwent RRP operation at our department from 1992 to
      2000 with a minimum 6 months of follow-up were assessed. Seventy two patients
      participated in the study. The continence status was classified as follows;
      patients who did not leak were considered as "continent", those who had leakage
      that occurred less frequent than or equal to once a day were regarded as
      "socially continent", and those who had more than once a day leakage were
      regarded as "incontinent". The correlation between urinary leakage, patients'
      satisfaction and pre-operative, peri-operative and post-operative factors were
      investigated. Univariate and multivariate analyses were done using Fisher's
      exact, chi-square, Student's-t and logistic regression tests. RESULTS: The mean
      age of patients at surgery was 63.9 years (49-76) with a follow-up period of 37.1
      months (6-97). Of these patients, 44% were continent, 48% were socially
      continent, 8% were incontinent. A total of 64 of 72 patients (89%) were satisfied
      with their final continence status, and 63 (87%) patients accepted to undergo the
      same surgery again if it is indicated. Pre-, peri- and post-operative factors did
      not influence the urinary leakage rates. Patients with nocturnal leakage,
      urgency, decreased urinary flow and patients who use pad (-s) were significantly
      less satisfied on univariate analysis, while only nocturnal leakage had a
      significant impact on patients' satisfaction on multivariate analysis.
      CONCLUSION: Urinary leakage and patients' satisfaction rates after RRP were 56%
      and 89%, respectively. None of the factors could predict the post-operative
      continence status. When evaluating the patients' satisfaction, only nocturnal
      leakage was found to have an adverse affect on multivariate analyses.

PMID- 17006735
TI  - Local anesthesia during transrectal ultrasonography-guided prostate biopsy: does
      it have any effect on sexual function?
AB  - INTRODUCTION: TRUS (Trans Rectal Ultra Sonographic)-guided biopsy of the prostate
      is the procedure of choice for prostate cancer diagnosis in urological clinical
      practice. TRUS-guided biopsies are associated with pain and anxiety and may
      interfere with sexual function and potency. The aim of this study was to evaluate
      whether local anesthesia during TRUS-guided prostate biopsies has any effect on
      the sexual behavior of patients and to compare the periprostatic infiltration
      with lidocaine to simple sonographic gel application in a randomized prospective
      trial. PATIENTS AND METHODS: A total of 62 consecutive patients were included in
      the study randomized in two groups; Group A (n = 30, control group) and Group B
      (n = 32, lidocaine infiltration group). Interviews regarding their sexual status
      were conducted at the time they were informed of the need for biopsy, at the time
      of biopsy and at two scheduled interviews following the biopsy. RESULTS: Similar
      results of sexual dysfunction were observed between the two groups. About 6% of
      patients experienced some degree of dysfunction in anticipation of biopsy (P >
      0.02 between the two groups) that was resolved by the end of the follow-up
      period. In total, only one Group B patient continued to show sexual dysfunction
      at the time of the last interview compared to two patients in Group A.
      CONCLUSIONS: Local infiltration with lidocaine does not seem to play a role in
      sexual dysfunction following prostate biopsies. Psychological factors influence
      patients and the urologist should be ready to inform and reassure both the
      patient and his family.

PMID- 17006736
TI  - Associations between coronary heart disease, obesity and histological prostate
      cancer.
AB  - OBJECTIVE: The present study investigates the possible associations between
      coronary heart disease and histological prostate carcinoma in autopsy material.
      MATERIAL AND METHOD: The material of our study, were 116 men between 55 years and
      98 years of age, who died in the period of August 2002-January 2005. The initial
      segment of the aorta and the prostate glands of all cadavers were removed while
      the initial 30 mm of the left and right coronary arteries and the peripheral zone
      of the prostate gland underwent pathologic examination. RESULTS: Of all subjects
      examined 71.8% had pathological findings suggesting advanced coronary heart
      disease. Twenty out of 116 cadavers were found with histological carcinoma in
      their prostate specimen. Among subjects positive for prostate cancer, 12 had died
      of cardiovascular diseases, while 16 had macroscopic evidence of advanced
      coronary artery obstructive disease, a finding that was confirmed on pathologic
      examination. Although most of the subjects had atheromatous lesions on the
      coronary arteries, the percentage of men with prostate cancer, which had advanced
      atheromatosis, was greater when compared to those of subjects without prostate
      cancer. The relation between the coronary artery obstructive disease severity and
      the presence of latent prostate cancer was statistically significant (P = 0.02).
      No statistically significant correlation was obtained between body mass index and
      the presence of prostate cancer. CONCLUSIONS: Our results indicate that there
      could be an association between coronary artery obstructive disease and prostate
      cancer, however due to the relatively low sample further studies are needed in
      order to confirm such findings.

PMID- 17006737
TI  - Hybridization, recombination, and the genetic basis of fitness variation across
      environments in Avena barbata.
AB  - We created Recombinant Inbred Lines (RILs) derived from a cross between ecotypes
      of Avena barbata associated with moist (mesic) and dry (xeric) habitats in
      California. Traits which were correlated with fitness across RILs mapped to the
      same Quantitative Trait Loci (QTLs) as fitness. However, different QTL affected
      fitness in different environments so that fitness was weakly correlated across
      environments. Recombination released considerable heritable variation both in
      fitness, and in ecologically relevant traits. Many traits showed transgressive
      segregation caused by recombination of QTL associated in repulsion phase in the
      parents. In addition, some traits were uncorrelated, allowing novel combinations
      of those traits to be created. Recombination also created heritable variation in
      reaction norms for at least one trait (root allocation). Altogether these results
      suggest that recombination can combine the most selectively advantageous genes
      and traits of the parents to produce broadly adapted genotypes that are capable
      of outperforming the parents. Indeed, two of the RILs showed higher fitness than
      the parental ecotypes across a range of environmental treatments in the
      greenhouse, but their superiority was less pronounced in the field. Although late
      generation recombinants exhibited hybrid breakdown, being less fit, on average,
      than the mid-parent, early generation hybrids appear to exhibit hybrid vigour
      through the expression of dominance effects in the heterozyotes. This vigour may
      offset the effects of hybrid breakdown in the early generations following a
      cross, enhancing the opportunity for recombination to create broadly adapted
      genotypes. We discuss the implications of these findings to the evolution of
      colonizing species.

PMID- 17006738
TI  - RNA unrestrained molecular dynamics ensemble improves agreement with experimental
      NMR data compared to single static structure: a test case.
AB  - Nuclear magnetic resonance (NMR) provides structural and dynamic information
      reflecting an average, often non-linear, of multiple solution-state
      conformations. Therefore, a single optimized structure derived from NMR
      refinement may be misleading if the NMR data actually result from averaging of
      distinct conformers. It is hypothesized that a conformational ensemble generated
      by a valid molecular dynamics (MD) simulation should be able to improve agreement
      with the NMR data set compared with the single optimized starting structure.
      Using a model system consisting of two sequence-related self-complementary
      ribonucleotide octamers for which NMR data was available, 0.3 ns particle mesh
      Ewald MD simulations were performed in the AMBER force field in the presence of
      explicit water and counterions. Agreement of the averaged properties of the
      molecular dynamics ensembles with NMR data such as homonuclear proton nuclear
      Overhauser effect (NOE)-based distance constraints, homonuclear proton and
      heteronuclear (1)H-(31)P coupling constant (J) data, and qualitative NMR
      information on hydrogen bond occupancy, was systematically assessed. Despite the
      short length of the simulation, the ensemble generated from it agreed with the
      NMR experimental constraints more completely than the single optimized NMR
      structure. This suggests that short unrestrained MD simulations may be of utility
      in interpreting NMR results. As expected, a 0.5 ns simulation utilizing a
      distance dependent dielectric did not improve agreement with the NMR data,
      consistent with its inferior exploration of conformational space as assessed by 2
      D RMSD plots. Thus, ability to rapidly improve agreement with NMR constraints may
      be a sensitive diagnostic of the MD methods themselves.

PMID- 17006739
TI  - The natural hosts for larvae and nymphs of Amblyomma neumanni and Amblyomma
      parvum (Acari: Ixodidae).
AB  - Based on the hypothesis that birds and rodents are important hosts for subadults
      of the Neotropical Amblyomma neumanni and Amblyomma parvum ticks, a survey of
      these type of hosts was carried out from July 2004 to March 2006, in Quilino (A.
      parvum) and Dean Funes (A. neumanni), Cordoba province, Argentina. Additionally,
      monthly tick counts were performed on cattle and goats with occasional tick
      search in other domestic hosts. Records of questing height of subadult ticks on
      vegetation were also carried out monthly. Rodents (n = 123) and birds (n = 122)
      captured in Dean Funes showed no infestation with A. neumanni. Apart of few
      nymphs found on horses, all larvae and nymphs of A. neumanni were on cattle with
      a larval prevalence and mean number of 22.2%, and 7.7 +/- 22.52, respectively,
      and a prevalence of nymphs of 47.8% with a mean of 7.9 +/- 18.49. The average
      questing height of larvae and nymphs of A. neumanni was 23.5 +/- 17.1 cm and 30.7
      +/- 26.7 cm, respectively. A total of 138 rodents and 130 birds were captured in
      Quilino but the Caviidae rodent Galea musteloides carried 99.3% of larvae and
      99.8% of nymphs of A. parvum, and no immature stages were detected on cattle,
      goat or vegetation. Tick counts on G. musteloides (n = 74) showed a prevalence of
      42% and a mean number of 9.9 +/- 24.83 for larvae, while nymphal infestation had
      a prevalence of 56.5% and a mean of 8.7 +/- 11.31. Cattle appear to be suitable
      hosts to sustain the complete cycle of A. neumanni in nature (adult ticks infest
      cattle too) and questing height of subadults indicates that they are expecting to
      feed on medium and large-sized mammals, such as cattle and other ungulates. At
      least in the study site, G. musteloides is the principal host for the survival
      strategy of A. parvum subadults; adult ticks are common on cattle and goats.
      These hosts are introduced in the Neotropics but A. neumanni was able to develop
      a surrogate cycle independent of native hosts while A. parvum still depends on
      probably primeval hosts to sustain their larvae and nymphs.

PMID- 17006740
TI  - Fusion of carbohydrate binding modules from Thermotoga neapolitana with a family
      10 xylanase from Bacillus halodurans S7.
AB  - Xylanase A of Thermotoga neapolitana contains binding domains both at the N- and
      C-terminal ends of the catalytic domain. In the N-terminal position it contains
      two carbohydrate-binding modules (CBM) which belong to family 22. These CBMs bind
      xylan but not to cellulose. The gene encoding the mature peptide of these CBMs
      was fused with an alkaline active GH10 xylanase from Bacillus halodurans S7 and
      expressed in Escherichia coli. The (His)(6) tagged hybrid protein was purified by
      immobilized metal affinity chromatography and characterized. Xylan binding by the
      chimeric protein was influenced by NaCl concentration and pH of the binding
      medium. Binding increased with increasing salt concentration up to 200 mM. Higher
      extent of binding was observed under acidic conditions. The fusion of the CBM
      structures enhanced the hydrolytic efficiency of the xylanase against insoluble
      xylan, but decreased the stability of the enzyme. The optimum temperature and pH
      for the activity of the xylanase did not change.

PMID- 17006741
TI  - Spider monkey, Muriqui and Woolly monkey relationships revisited.
AB  - The taxonomic relationships among the four genera of the Atelidae family,
      Alouatta (Howler), Ateles (Spider), Lagothrix (Woolly) and Brachyteles (Muriqui),
      have been the subject of great debate. In general, almost all authors agree with
      the assignment of Howler monkeys as the basal genus, either in its own tribe
      Alouattini or in the subfamily Alouattinae, but they disagree on the associations
      among the other members of the family. Muriquis have been grouped with Spider
      monkeys based on the fact that they share various behavioral and morphological
      characteristics. Cladistic analyses using morphological, biochemical, karyotype
      and behavioral characteristics depicted a phylogenetic tree that places Howler as
      the basal genus and the remaining genera in an unresolved politomy. More recent
      studies using molecular data have suggested that Muriqui and Woolly monkeys are
      sister groups. However, a recent study based on nuclear and mtDNA argued that
      politomy is what best represents the relationships among Spider, Woolly and
      Muriqui. To contribute to this debate we have added new data from two nuclear
      genes, Transferrin and von Willebrand Factor, and using an alignment of 17,997 bp
      we demonstrate that a total analysis strongly supports the Muriqui-Woolly clade.
      A gene-to-gene approach showed that four of the eight nuclear genes provide
      support for the Muriqui-Woolly clade, two strongly and two moderately, while none
      of the eight genes provide support for any alternative arrangement. The
      mitochondrial genes were not able to resolve the politomy. A possible reason for
      the difficulty in resolving atelid relationships may be the short period of time
      separating each cladogenetic event in the evolutionary process that shaped this
      family.

PMID- 17006742
TI  - Is tumor size the best predictor of outcome for papillary thyroid cancer?
AB  - BACKGROUND: There are many risk classification schemes that determine both
      treatment and outcome for patients with papillary thyroid cancer. Most of these
      formulas often utilize tumor size as the key predictor of outcome. Furthermore,
      there is no clear consensus regarding the treatment of small papillary cancers.
      Therefore, we reviewed our experience in order to determine which factors best
      predict outcome for papillary thyroid cancer. In addition, we sought to establish
      a tumor size threshold beyond which papillary cancers require treatment. METHODS:
      From May 1994 to October 2004, 174 patients underwent surgery for papillary
      thyroid cancer (PTC) at our institution. These patients were divided into five
      groups based on tumor size. The data from these groups were analyzed utilizing
      ANOVA, Chi-square and linear regression analysis. RESULTS: The mean age of the
      patients was 42 +/- 1 years and 126 (72%) were female. Mean tumor size was 17.2
      +/- 1.1 mm. The overall outcome was quite good with a survival rate of 97% and a
      recurrence rate of 12%. On univariate analysis, there was no difference amongst
      the groups in regards to age or gender. However, there was a significantly higher
      incidence of lymph node metastasis amongst those with the largest tumors.
      Consequently, those patients with the largest tumors were treated more
      aggressively, with 75% undergoing total thyroidectomies and 85% receiving
      radioactive iodine therapy. However, on univariate and multivariate analysis,
      tumor size was not shown to correlate with higher recurrence. Rather, the only
      factor associated with a greater recurrence rate was the presence of lymph node
      metastases. CONCLUSION: At our institution, the recurrence rates for PTC were
      similar for all sizes of tumors. Furthermore, presence of metastatic disease at
      the time of diagnosis, rather than tumor size, seems to be a better predictor of
      recurrence and outcome.

PMID- 17006743
TI  - Stimulation of expression of the intestinal glutamine transporter ATB0 in tumor
      bearing rats.
AB  - BACKGROUND: Glutamine supplementation ameliorates host catabolic response in
      tumor bearing states. The purpose of this in vivo study was to investigate
      intestinal glutamine transport and expression of glutamine transporter ATB(0) in
      methyl-cholanthrene (MCA)-sarcoma bearing rats. METHODS: Fisher-344 rats
      underwent subcutaneous flank implantation of MCA-sarcoma cells (saline as
      control) and were pair-fed an equal quantity of chow as controls, to account for
      tumor-induced anorexia, until tumors reached 10 or 20% body weight. Intestinal
      mucosal brush border membrane [3H]-Glutamine transport was measured. Glutamine
      transporter ATB(0) mRNA and protein levels were measured by real-time PCR and
      western blot techniques, respectively. RESULTS: Glutamine transport activity
      across the intestinal brush border membrane (BBM) was 3.7-fold higher in tumor
      bearing rats (TBR) than in controls (TBR 153 +/- 22.6 vs. Control 41.9 +/- 9.7
      pmol/mg protein/10s, P < .01). Transporter ATB(0) mRNA levels were 1.4-fold
      higher in tumor-bearing rats (Relative value TBR .61 +/- .12 vs. Control .43 +/-
      .1, P < .05). A 1.4-fold increase in transporter ATB(0) protein levels was
      observed in the tumor-bearing rats (Relative value TBR .52 +/- .07 vs. Control
      .37 +/- .04, P < .05). Circulating aortic plasma glutamine levels were 1.3-fold
      higher in tumor bearing rats ([Glutamine] = .63 +/- .02 Control vs. [Glutamine] =
      .74 +/- .01 mmol/l TBR, P < .0001). Portal venous plasma glutamine levels were
      also higher in tumor bearing rats ([Glutamine] = .47 +/- .01 Control vs.
      [Glutamine] = .60 +/- .02 mmol/l TBR, P < .0001). CONCLUSION: Intestinal brush
      border membrane glutamine transport activity, transporter ATB(0) mRNA and protein
      levels are up-regulate in tumor-bearing rats.

PMID- 17006744
TI  - The estimated impact of fungi on nutrient dynamics during decomposition of
      Phragmites australis leaf sheaths and stems.
AB  - Decomposition of culms (sheaths and stems) of the emergent macrophyte Phragmites
      australis (common reed) was followed for 16 months in the litter layer of a
      brackish tidal marsh along the river Scheldt (the Netherlands). Stems and leaf
      sheaths were separately analyzed for mass loss, litter-associated fungal biomass
      (ergosterol), nutrient (N and P), and cell wall polymer concentrations (cellulose
      and lignin). The role of fungal biomass in litter nutrient dynamics was evaluated
      by estimating nutrient incorporation within the living fungal mass. After 1 year
      of standing stem decay, substantial fungal colonization was found. This
      corresponded to an overall fungal biomass of 49 +/- 8.7 mg g(-1) dry mass. A
      vertical pattern of fungal colonization on stems in the canopy is suggested. The
      litter bag experiment showed that mass loss of stems was negligible during the
      first 6 months, whereas leaf sheaths lost almost 50% of their initial mass during
      that time. Exponential breakdown rates were -0.0039 +/- 0.0004 and -0.0026 +/-
      0.0003 day(-1) for leaf sheaths and stems, respectively (excluding the initial
      lag period). In contrast to the stem tissue--which had no fungal colonization-
      leaf sheaths were heavily colonized by fungi (93 +/- 10 mg fungal biomass g(-1)
      dry mass) prior to placement in the litter layer. Once being on the sediment
      surface, 30% of leaf sheath's associated fungal biomass was lost, but ergosterol
      concentrations recovered the following months. In the stems, fungal biomass
      increased steadily after an initial lag period to reach a maximal biomass of
      about 120 mg fungal biomass g(-1) dry mass for both plant parts at the end of the
      experiment. Fungal colonizers are considered to contain an important fraction of
      nutrients within the decaying plant matter. Fungal N incorporation was estimated
      to be 64 +/- 13 and 102 +/- 15% of total available N pool during decomposition
      for leaf sheaths and stems, respectively. Fungal P incorporation was estimated to
      be 37 +/- 9 and 52 +/- 15% of total available P during decomposition for leaf
      sheaths and stems, respectively. Furthermore, within the stem tissue, fungi are
      suggested to be active immobilizers of nutrients from the external environment
      because fungi were often estimated to contain more than 100% of the original
      nutrient stock.

PMID- 17006745
TI  - Age does not affect airway pH and ammonia as determined by exhaled breath
      measurements.
AB  - Measurement of airway pH has been used as a diagnostic and monitoring tool in a
      variety of pulmonary diseases in adults. These diseases occur across a wide age
      range. Few investigations have addressed the effects of aging on airway pH and
      ammonia. The aim of this study was to determine whether exhaled breath condensate
      (EBC) measurements of pH and ammonia differ in older and younger populations of
      normal subjects. Twenty-three normal younger individuals (median age-24 years)
      and 25 normal older participants (median age-72 years) were investigated by
      measuring EBC for pH and ammonia using recommended methodologies. EBC ammonia and
      pH values were not significantly different between younger and older individuals.
      Thus, we conclude that EBC ammonia and pH do not appear to be affected by age.

PMID- 17006746
TI  - Single dose of tiotropium improves the 6-minute walk distance in chronic
      obstructive pulmonary disease.
AB  - The aim of this study was to evaluate the effect of a single dose of tiotropium
      on the exercise capacity of stable chronic obstructive pulmonary disease (COPD)
      patients. The study was a randomized, placebo-controlled, double-blind, cross
      over study. Forty-four stable COPD patients with moderate to severe airway
      obstruction were selected according to the GOLD criteria. The regular
      anticholinergic therapies of the patients were interrupted one week before the
      test. In the morning hours of the first day, half the group was given one capsule
      (18 mcg) of tiotropium and the other half was given placebo as inhalation using
      the HandiHaler device. Before and 120 min after the medication, the 6-min walk
      test was performed. Oxygen saturation, modified Borg dyspnea ratings, blood
      pressure, and heart rate were recorded before and after the test. The same
      procedure was repeated at the same time on the third day but this time the
      patients were given placebo if they used tiotropium on the first day and vice
      versa. Before using tiotropium or placebo there was no difference between 6-min
      walk distances. The 6-min walk distance after the use of tiotropium (429.3 +/-
      70.6 m) was significantly longer than that after the use of placebo (414.7 +/-
      74.6 m). The changes in Borg dyspnea ratings and arterial oxygen saturation
      values with tiotropium and placebo use were not significant. We conclude that
      exercise capacity might be improved by using a single-dose tiotropium inhalation
      in moderate to severe COPD patients.

PMID- 17006747
TI  - Cardiopulmonary support in duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked, rapidly progressive myopathy
      affecting the limb muscles, the respiratory muscles, the heart, the intestines,
      and the brain. Since about 90% of DMD patients die from muscular respiratory
      failure or cardiomyopathy, early and adequate therapy is essential. Ventilatory
      failure from muscle weakness requires mechanical support for ventilation and
      coughing as soon as there is symptomatic nocturnal hypoventilation. Today
      noninvasive positive-pressure ventilation (NIPPV) is the method of choice for
      supportive long-term mechanical ventilation in DMD. For assisted coughing,
      various methods are available, among which the mechanical in-exsufflator is the
      most widely used device. There is large nonrandomized clinical trial evidence
      that NIPPV improves quality of life and prolongs the lives of DMD patients if
      medical, social, economic, and ethical issues, raised by the availability of long
      term NIPPV, are adequately addressed. Cardiac involvement in DMD manifests as
      impulse generation or impulse conduction abnormalities or cardiomyopathy. Cardiac
      abnormalities in DMD respond well to adequate therapy. Though DMD is ultimately a
      fatal disease, quality of life and life expectancy can be markedly improved if
      cardiopulmonary manifestations are adequately treated.

PMID- 17006748
TI  - Inhaled fluticasone and salmeterol suppress eosinophilic airway inflammation in
      chronic obstructive pulmonary disease: relations with lung function and
      bronchodilator reversibility.
AB  - The aim of this study was to determine whether combined inhaled corticosteroids
      and long-acting beta(2) agonists can suppress eosinophilic inflammation in
      chronic dostructive plumonary disease (COPD) and to investigate the association
      between the level of eosinophilia and the degree of bronchodilator reversibility.
      Sixty-two patients with stable COPD (forced expiratory volume in 1 [FEV(1)] of
      30%-70% predicted before bronchodilation) were enrolled from our outpatient
      clinic. Patients received inhaled fluticasone (100 microg)/salmeterol (50 microg)
      twice daily for two months. Lung function measurements, bronchodilator tests, and
      sputum induction were performed. The number of inflammatory cells and mediators,
      including interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and
      eosinophilic cationic protein (ECP), were measured. Treatment with inhaled
      fluticasone and salmeterol significantly suppressed eosinophilic inflammation in
      COPD patients with sputum eosinophilia (mean 8.9% +/- 2.0% vs. 1.6% +/- 0.5%, p =
      0.003), but insignificant differences in FEV(1) and FVC between patients with and
      without eosinophilia suggested that suppression of eosinophilic inflammation had
      no effect on FEV(1) or FVC. Reduction in the percentage of eosinophils was
      significantly correlated with decreased levels of ECP (r = 0.48, p < 0.001).
      Levels of neutrophils, IL-8, and TNF-alpha were not affected. Sputum eosinophilia
      was not related to the degree of bronchodilator reversibility. The degree of
      bronchodilator reversibility did not predict the increase in FEV(1) and FVC after
      treatment with inhaled corticosteroids/long-acting beta(2) agonists. Suppression
      of eosinophilic inflammation and bronchodilator responsiveness indices were not
      correlated with clinical outcomes in COPD patients treated with inhaled
      corticosteroids/long-acting beta(2) agonists.

PMID- 17006749
TI  - A case of alpha-thalassemia-2 associated with pulmonary infarction.
AB  - Pulmonary infarction is an entity of medical significance that develops
      concurrently in beta-thalassemia but not in alpha-thalassemia. The reason for
      this difference is yet to be elucidated. We have evaluated a 21-year-old male
      alpha-thalassemia-2 patient who had profound microcytic anemia and pulmonary
      infarction. Analysis of the alpha-globin gene revealed -alpha3.7/alpha alpha
      genotype. His mother also had the same heterozygous gene deletion, though she had
      neither anemia nor pulmonary infarction. Since the patient had no other
      predisposition to pulmonary infarction, it is suggested that there is a close
      etiologic relationship between morphologic abnormality of the erythrocytes caused
      by alpha-thalassemia-2 and development of pulmonary infarction.

PMID- 17006750
TI  - Immune cell infiltration and broncovascular remodeling after nitric acid nasal
      instillation in a mouse bronchiolitis obliterans model.
AB  - Immune cell airway infiltration and the bronchovascular remodeling process have
      shown to be promising in the understanding of bronchiolitis obliterans (BO)
      pathogenesis. In this study we sought to validate the importance of immune cells,
      whether diffusely distributed or forming lymphoid follicles, collagen density,
      and vascular factors. Eight weeks after a single nitric acid (NA) nasal
      instillation, lung changes were characterized by lumen distortion, epithelial
      layer folding, reduction or total obliteration of terminal bronchiole (TB) lumen,
      and wall thickness increase. The morphologic changes in the TB and TA (terminal
      artery) lumen coincide with the measurement difference in the three groups. The
      TB diameter and lumen were significantly decreased in BO when compared with non
      BO lungs (0.76 +/- 0.05 microm vs. 0.81 +/- 0.05 microm and 12,286.13 +/- 378.83
      microm vs. 18,182.27 +/- 5,593.98 microm, p = 0.05 and p = 0.01, respectively).
      Equally significant was the increase in TB thickness in BO when compared with the
      non-BO group (201.72 +/- 35.75 microm vs. 149.75 +/- 40.61 microm, p = 0.007).
      The morphologic changes in immune cells seen in TB, TA, and bronchus-associated
      lymphoid tissue (BALT) also coincide with the quantification differences observed
      in the three groups. We concluded that immune cell infiltration and
      collagen/vascular remodeling are related to the spectrum of histologic changes in
      a BO nasal-induced model in mice and may be an appropriate target for prospective
      studies of human bronchiolitis.

PMID- 17006751
TI  - Structural features of epithelial remodeling in usual interstitial pneumonia
      histologic pattern.
AB  - Epithelial remodeling probably contributes to parenchymal deterioration in usual
      interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF), but understanding
      its mechanisms is still a challenge. The aim of our study was to examine
      apoptosis and the epithelial changes in the histologic pattern of UIP. After
      immunohistochemical staining we quantified the content of type I cells, type II
      cells, surfactant-A protein, bcl-2, and Fas-ligand (Fas-L) in control and
      alveolar collapse, fibroblastic foci, and honeycomb in UIP areas of 23 open lung
      biopsies. A significant association was found between epithelial changes and
      parenchymal deterioration (p < 0.05). Type I epithelial cell density was similar
      between control (1.7 +/- 0.7%) and UIP alveolar collapse areas (1.8 +/- 0.6%) but
      decreased progressively in fibroblastic foci zones (0.8 +/- 0.4%) and honeycomb
      changes (0.4 +/- 0.3%). Type II cell density increased from control (25.6 +/-
      8.3%) to areas of alveolar collapse (34.5 +/- 11.4%), then decreased toward
      fibroblastic foci (15.4 +/- 6.0%) and honeycomb change areas (23.1 +/- 8.6%). The
      surfactant-A protein increased from control (6.7 +/- 3.2%) to areas of alveolar
      collapse (31.1 +/- 9.5%) and decreased toward fibroblastic foci (14.5 +/- 4.9%)
      and honeycomb change areas (21.1 +/- 8.9%). Fas-L positive epithelial cell
      density presented a progressive decline from control (48.5 +/- 9.5%), alveolar
      collapse (37.9 +/- 12.4%), fibroblastic foci (27.4 +/- 6.8%), and honeycomb
      change areas (21.9 +/- 6.5%). A similar decline in density was found for bcl-2
      positive epithelial cells from control (20.4 +/- 2.7%), alveolar collapse (18.9
      +/- 5.1%), and fibroblastic foci areas (13.8 +/-2.9%), then increased honeycomb
      change areas (16.3 +/- 2.8%). We conclude that loss of the nuclear (bcl-2) and
      membrane (Fas-L) regulation of normal cell population density and suppression of
      cell death by apoptosis in UIP may be a determinant of the abnormal
      epithelial/parenchymal remodeling in UIP.

PMID- 17006752
TI  - An unusual cause of dyspnea in a patient with relapsing breast cancer.
AB  - Bilateral diaphragmatic paralysis (BDP) is usually caused by anatomic lesions of
      both phrenic nerves or generalized neurologic diseases. BDP has also been
      observed during and after infections, associated with mediastinal tumors, or may
      have an idiopathic etiology. A 57-year-old woman with breast cancer had
      progressive dyspnea that worsened when in the supine position. Lung function
      tests and phrenic nerve stimulation revealed bilateral diaphragmatic paralysis.
      Clinical suspicion of BDP should always be raised in patients suffering from
      progressive dyspnea and orthopnea. Determination of (VC) when standing and in the
      supine position and measurement of trandiaphragmatic pressure should reveal this
      uncommon diagnosis.

PMID- 17006753
TI  - Acute renal failure associated with gefitinib therapy.

PMID- 17006754
TI  - Evaluation of Goldmann applanation tonometry using a nonlinear finite element
      ocular model.
AB  - Goldmann applanation tonometry (GAT) is the internationally accepted standard for
      intra-ocular pressure (IOP) measurement, which is important for the diagnosis of
      glaucoma. The technique does not consider the effect of the natural variation in
      the corneal thickness, curvature and material properties. As these parameters
      affect the structural resistance of the cornea, their variation is expected to
      lead to inaccuracies in IOP determination. Numerical Analysis based on the finite
      element method has been used to simulate the loading conditions experienced in
      GAT and hence assess the effect of variation in corneal parameters on GAT IOP
      measurements. The analysis is highly nonlinear and considers the hyper-elastic J
      shaped stress-strain properties of corneal tissue observed in laboratory tests.
      The results reveal a clear association between both the corneal thickness and
      material properties, and the measured IOP. Corneal curvature has a considerably
      lower effect. Similar trends have been found from analysis of clinical data
      involving 532 patients referred to the Glaucoma Unit at Moorfields Hospital, and
      from earlier mathematical analyses. Nonlinear modelling is shown to trace the
      behaviour of the cornea under both IOP and tonometric pressure, and to be able to
      provide additional, and potentially useful, information on the distribution of
      stress, strain, contact pressure and gap closure.

PMID- 17006755
TI  - Mechanical response of a calcified plaque model to fluid shear force.
AB  - Vascular calcification is associated with atherosclerosis, but whether it
      mechanically affects plaque stability remains controversial. To assess the effect
      of mineralization on plaque vulnerability to mechanical shear stress, we applied
      fluid shear to cultures of calcifying vascular cells (CVC), a subpopulation of
      smooth muscle cells that spontaneously mineralize. CVC cultures containing
      nodules were treated for 10 days with vehicle control or beta-glycerophosphate
      (BGP) to accelerate mineralization. Cultures were placed in a parallel-plate flow
      system and were subjected to increasing fluid shear stress (4.9 dyn/cm(2)/min up
      to 400 dyn/cm(2)). The number of nodules remaining attached was recorded every 10
      min. Results showed that control cultures and BGP-treated cultures, which
      contained significantly greater calcium mineral than control cultures, had
      similar detachment thresholds (50-100 dyn/cm(2)), with linear portions of their
      stress/detachment curves from 100 to 275 dyn/cm(2). Based on repeated measure
      analysis of variance, BGP-treated nodules were no more likely to detach at a
      given shear than controls, although they showed a trend toward greater stability.
      Thus, calcification does not appear to increase plaque vulnerability to fluid
      shear stress, although it may contribute to a slight stabilization. This model
      may represent the first in vitro model of mechanical rupture of atherosclerotic
      plaque.

PMID- 17006756
TI  - Coexistence of the loss of heterozygosity at the PTEN locus and HER2
      overexpression enhances the Akt activity thus leading to a negative progesterone
      receptor expression in breast carcinoma.
AB  - Serine/threonine kinase Akt/PKB is known to regulate divergent cellular
      processes, including apoptosis, proliferation, differentiation, and metabolism.
      Akt is activated by a variety of stimuli, through such growth factor receptors as
      HER2, in phosphoinositide-3-OH kinase (PI3K)-dependent manner. A loss of
      phosphatase and tensin homolog deleted on chromosome 10 (PTEN) function also
      activates Akt. It has recently been shown that Akt activation is associated with
      a worse outcome among endocrine treated breast cancer patients and that it also
      inhibits the progesterone receptor (PR) expression via the PI3K/Akt pathway in
      breast cancer cells. Therefore, the PI3K/Akt signaling pathway has recently
      attracted considerable attention as a new target for effective therapeutic
      strategies. In the present study, we investigated the relationship between Akt
      activation and either HER2 overexpression or PTEN gene alteration, as well as the
      PR expression. We analyzed the incidence of LOH at the PTEN locus in 138 breast
      cancer patients, using our new system for microsatellite analysis, called high
      resolution fluorescent microsatellite analysis (HRFMA). We showed Akt activation
      to significantly correlate with HER2 overexpression or LOH at the PTEN gene locus
      while inversely correlating with the PR expression. In addition, when LOH at the
      PTEN gene locus and HER2 overexpression occurred simultaneously, the incidence of
      Akt activation and reduced PR expression was significant. The association between
      Akt activation and PR negative expression was observed even in the ER-positive
      cases. Our results suggest that simultaneous PTEN LOH and HER2 overexpression
      enhances Akt activation and may thus lead to a negative PR expression.

PMID- 17006758
TI  - Possible mechanisms of neurodegeneration in schizophrenia.
AB  - Brain morphological alterations in schizophrenic patients have led to the
      neurodevelopmental hypothesis of schizophrenia. On the other hand, a progressive
      neurodegenerative process has also been suggested and some follow-up studies have
      shown progressive morphological changes in schizophrenic patients. Several
      neurotransmitter systems have been suggested to be involved in this disorder and
      some of them could lead to neuronal death under certain conditions. This review
      discusses some of the biochemical pathways that could lead to neurodegeneration
      in schizophrenia showing that neuronal death may have a role in the etiology or
      natural course of this disorder.

PMID- 17006759
TI  - 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) induces cell death through
      caspase-independent mechanism in A172 human glioma cells.
AB  - 15-Deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ(2)) is a naturally occurring
      cyclopentenone metabolite of prostaglandin D(2) (PGD(2)) and is known as a
      specific potent ligand for the peroxisome proliferators activator receptor-gamma
      (PPARgamma). 15d-PGJ(2) inhibits cell growth and induces apoptosis in a number of
      different cancer cells. However, the underlying mechanism by which 15d-PGJ(2)
      induces cell death remains to be defined. The present study was undertaken to
      determine the effect of 15d-PGJ(2) on cell death in A172 human glioma cells. 15d
      PGJ(2) caused reactive oxygen species (ROS) generation. 15d-PGJ(2)-induced ROS
      production and cell death were prevented by the antioxidant N-acetylcysteine.
      Activation of mitogen-activated protein kinases (MAPK) was not observed in cells
      treated with 15d-PGJ(2 )and inhibitors of MAPK subfamilies also were not
      effective in preventing 15d-PGJ(2)-induced cell death. 15d-PGJ(2) treatment
      caused mitochondrial dysfunction, as evidenced by depolarization of mitochondrial
      membrane potential. 15d-PGJ(2) induced caspase activation at 24 h of treatment,
      but the 15d-PGJ(2)-induced cell death was not prevented by caspase inhibitors.
      The antiapoptotic protein XIAP levels and release of apoptosis inducing factor
      (AIF) into the cytosol were not altered by 15d-PGJ(2) treatment. Taken together,
      these findings indicate that 15d-PGJ(2) triggers cell death through a caspase
      independent mechanism and ROS production and disruption of mitochondrial membrane
      potential play an important role in the 15d-PGJ(2)-induced cell death in A172
      human glioma cells.

PMID- 17006760
TI  - Increased expression of p130 in Alzheimer disease.
AB  - A number of recent findings support the notion of mechanistic parallels between
      Alzheimer disease (AD) and oncogenic processes, specifically, that neurons in AD,
      like cancer cells, display aberrant mitotic cell cycle re-entry. However, the
      mechanism that drives postmitotic neurons to reenter cell cycle remains elusive.
      In this study, we focused on the retinoblastoma-related protein p130 in AD. p130
      is a transcriptional regulator that complexes with E2F4/5 in the nucleus and
      suppresses genes that regulate entry into the cell cycle. Interestingly, our
      results show that there are increases in p130 in cytoplasm of susceptible
      pyramidal neurons as well as neuroglia, often surrounding senile plaques, and
      within Hirano bodies in AD. By marked contrast, p130 is found at background
      levels in non-diseased, age-matched controls. Our data suggest that, despite its
      upregulation, the aberrant localization of p130 to the neuronal cytoplasm
      facilitates neuronal cell cycle re-entry in AD.

PMID- 17006761
TI  - Mini review: immune response to myelin-derived sulfatide and CNS-demyelination.
AB  - Here we briefly review our understanding of the immune response to myelin-derived
      glycolipids during an inflammatory autoimmune response in the central nervous
      system (CNS). We focus primarily on the recognition of the self-glycolipid
      sulfatide by a distinct population of non-invariant NK T cells. The results of
      studies we have obtained so far in investigating the presentation of sulfatide by
      CNS-resident cells including microglia and their interactions with T cells
      indicate that this pathway might be successfully targeted for the treatment of
      autoimmune demyelination in multiple sclerosis.

PMID- 17006765
TI  - Pro-angiogenic cytokines and their role in tumor angiogenesis.
AB  - The development of solid tumors depends upon an adequate supply of blood. This
      can be achieved by way of co-option of preexisting blood vessels and by the
      induction of angiogenesis. During the past 30 years, tumor angiogenesis had been
      found to play a crucial role in the progression of solid tumors. Tumor
      angiogenesis was found to be induced by a variety of pro-angiogenic cytokines of
      which the best characterized is vascular endothelial growth factor (VEGF).
      Indeed, the first FDA approved anti-angiogenic drug for the treatment of cancer
      is Avastin, a neutralizing antibody directed against VEGF. This review focuses on
      cytokines which have been reported to induce tumor angiogenesis.

PMID- 17006764
TI  - Evidence of mechanoelectric feedback in the atria of patients with
      atrioventricular nodal reentrant tachycardia.
AB  - OBJECTIVE: Patients with atrioventricular nodal reentrant tachycardia (AVNRT)
      could serve as a clinical model to study the effects of mechanical stretch in the
      electrical properties of atrial myocardium. MATERIALS AND METHODS: We studied 14
      patients with AVNRT. Peak, mean and minimal atrial pressures, atrial
      refractoriness (ERP) in the right atrial appendage and high right atrial lateral
      wall and monophasic action potential duration at 90% of repolarisation (MAPd90)
      in the right atrial appendage were assessed during atrial pacing at 500 and 400
      ms and after 2 min of pacing at the tachycardia cycle length. Measurements were
      repeated from the same positions after ventricular pacing at the same cycle
      lengths and after 2 min of tachycardia. Susceptibility to atrial fibrillation
      (AF) was assessed by noting whether AF was induced during ERP evaluation.
      RESULTS: Atrial pressure showed a statistically significant increase during
      ventricular pacing compared to baseline. This increase remained substantially
      unchanged when the tachycardia was induced. A significant reduction in atrial ERP
      and MAPd90 was also observed during ventricular pacing at all cycle lengths
      compared to atrial pacing. Two minutes of spontaneous tachycardia were enough to
      change the atrial ERP and MAPd90 to values significantly lower than those during
      atrial pacing at the cycle length of tachycardia. During the ERP evaluation AF
      was induced more often during the tachycardia (28%) than during ventricular (14%)
      and atrial pacing (0%). CONCLUSION: In AVNRT patients, ventricular pacing and
      reentrant tachycardia significantly increase right atrial pressures and
      subsequently shorten ERP and MAPd90, leading to an enhanced propensity for AF.

PMID- 17006767
TI  - "It's like going through an earthquake": anthropological perspectives on
      depression among Latino immigrants.
AB  - Depression is one of the most prevalent mental illnesses in the community and is
      responsible for a significant amount of disability. According to epidemiological
      and primary care studies, Latinos suffer from depression at high rates. This
      paper examines in depth Latinos' conceptions of depression and their attitudes
      towards and expectations of mental health treatment. The aim of this paper is to
      summarize several qualitative studies examining Latinos' cultural understandings
      of mental health in general and depression in particular, as well as to obtain
      information about the barriers to care that this community experienced. The
      results are a compilation of findings from four different research projects in
      New Jersey and New York that examined diverse Latinos' conceptions of mental
      health, treatment and barriers to care.

PMID- 17006763
TI  - Regional expression of key cell cycle proteins in brain from subjects with
      amnestic mild cognitive impairment.
AB  - Mild cognitive impairment (MCI) is regarded as a transition stage between the
      cognitive changes of normal aging and the more serious problems caused by
      Alzheimer's disease (AD). Previous studies had demonstrated increased expression
      of cell cycle proteins in AD brain. In the present study, we have analyzed the
      expression of the cell cycle proteins, CDK2, CDK5 and cyclin G1 in hippocampus
      and inferior parietal lobule (IPL) in subjects with amnestic mild cognitive
      impairment and control using Western blot analysis. The expression of CDK2, CDK5
      and cyclin G1 were found to be significantly increased in MCI hippocampus as well
      as in IPL compared to control brain. These results suggest that some cells may
      have re-entered the cell cycle. However, the expression of CDK2 and CDK5 is
      greater in MCI hippocampus compared to those of MCI IPL, and hippocampus is a
      region that is severely affected by AD pathology. Since these proteins are
      involved directly or indirectly in microtubule destabilization and
      hyperphosphorylation of tau, and also in APP processing we hypothesize that cell
      cycle disturbance may be important contributor in the pathogenesis of AD.

PMID- 17006762
TI  - Kinetic parameters and lactate dehydrogenase isozyme activities support possible
      lactate utilization by neurons.
AB  - Lactate is potentially a major energy source in brain, particularly following
      hypoxia/ischemia; however, the regulation of brain lactate metabolism is not well
      understood. Lactate dehydrogenase (LDH) isozymes in cytosol from primary cultures
      of neurons and astrocytes, and freshly isolated synaptic terminals (synaptosomes)
      from adult rat brain were separated by electrophoresis, visualized with an
      activity-based stain, and quantified. The activity and kinetics of LDH were
      determined in the same preparations. In synaptosomes, the forward reaction
      (pyruvate + NADH + H(+ )--> lactate + NAD(+)), which had a V (max) of 1,163
      micromol/min/mg protein was 62% of the rate in astrocyte cytoplasm. In contrast,
      the reverse reaction (lactate + NAD(+ )--> pyruvate + NADH + H(+)), which had a V
      (max) of 268 micromol/min/mg protein was 237% of the rate in astrocytes. Although
      the relative distribution was different, all five isozymes of LDH were present in
      synaptosomes and primary cultures of cortical neurons and astrocytes from rat
      brain. LDH1 was 14.1% of the isozyme in synaptic terminals, but only 2.6% and
      2.4% in neurons and astrocytes, respectively. LDH5 was considerably lower in
      synaptic terminals than in neurons and astrocytes, representing 20.4%, 37.3% and
      34.8% of the isozyme in these preparations, respectively. The distribution of LDH
      isozymes in primary cultures of cortical neurons does not directly reflect the
      kinetics of LDH and the capacity for lactate oxidation. However, the kinetics of
      LDH in brain are consistent with the possible release of lactate by astrocytes
      and oxidative use of lactate for energy in synaptic terminals.

PMID- 17006766
TI  - The sero-prevalence of antibodies to trypanosoma cruzi in Latin American refugees
      and immigrants to Canada.
AB  - BACKGROUND: Chagas' disease is caused by infection with the protozoan agent
      Trypanosoma cruzi. An estimated sixteen to eighteen million people are infected
      in Latin America. Outside of endemic regions, Chagas' disease may be transmitted
      through the transfusion of infected blood components, congenital infection and
      organ transplantation. We sought to determine the sero-prevalence of antibodies
      to T. cruzi in a community sample of Latin American refugees and immigrants to
      Canada. METHODS: This was a sero-prevalence study in Latin American refugees and
      immigrants living in Canada. Eligible subjects were born in South America,
      Central America or in Mexico. Participants were recruited from a variety of
      community settings, as well as from medical clinics. Serum was tested by enzyme
      linked immunoassay for antibodies to T. cruzi. RESULTS: A total of 102
      participants were enrolled. One sample tested positive for antibodies for T.
      cruzi. The seroprevalence in our sample was 1.0% (95% CI: 0.2%- 5.3%).
      INTERPRETATION: We found a low sero-prevalence of Chagas' disease in a community
      sample of Latin American immigrants and refugees. Physicians who treat Latin
      American immigrants should consider the risk profile and clinical status of the
      individual in their decision to screen for Chagas' disease.

PMID- 17006769
TI  - Percutaneous penetration of methyl nicotinate from ointments using the laser
      Doppler technique: bioequivalence and enhancer effects.
AB  - Laser Doppler flowmetry (LDF) may be used to quantify erythema response as a
      result of an increased cutaneous microcirculation induced by methyl nicotinate
      (MN). Bioequivalence of a test and a standard preparation (vehicles: light
      mineral oil and medium chain triglycerides, respectively) was confirmed according
      to the pilot study of the FDA Guidance for Industry "Topical dermatologic
      corticosteroids: In Vivo bioequivalence" applying the staggered application and
      synchronized removal method for one defined concentration. Furthermore, the
      influence of penetration enhancers (5% w/w Dimethylsulfoxide (DMSO) and 10% w/w
      diethylene glycol monoethyl ether) on MN penetration was investigated. It was
      shown that DMSO and diethylene glycol monoethyl ether altered cutaneous
      microcirculation and thus MN penetration in comparison to the standard
      formulation. However, true penetration enhancement could only be proved with
      diethylene glycol monoethyl ether resulting from an improved drug solubility in
      the skin which was confirmed by attenuated total reflectance fourier transform
      infrared spectroscopy (ATR-FTIR). Increased MN penetration by DMSO was only
      caused by thermodynamic effects, i.e. a decreased drug solubility in the vehicle.

PMID- 17006771
TI  - Birth weight and infant growth: optimal infant weight gain versus optimal infant
      weight.
AB  - OBJECTIVE: Infant growth assessment often focuses on "optimal" infant weights and
      lengths at specific ages, while de-emphasizing infant weight gain. Objective of
      this study was to examine infant growth patterns by measuring infant weight gain
      relative to birth weight. METHODS: We conducted this study based on data
      collected in a prospective cohort study including 3,302 births with follow up
      examinations of infants between the ages of 8 and 18 months. All infants were
      participants in the Louisiana State Women, Infant and Children Supplemental Food
      Program between 1999 and 2001. Growth was assessed by infant weight gain
      percentage (IWG%, defined as infant weight gain divided by birth weight) as well
      as by mean z-scores and percentiles for weight-for-age, length-for-age, and
      weight-for-length calculated based on growth charts published by the U.S. Centers
      for Disease Control (CDC). RESULTS: An inverse relationship was noted between
      birth weight category and IWG% (from 613.9% for infants with birth weights <1500
      g to 151.3% for infants with birth weights of 4000 g or more). In contrast, low
      birth weight infants had lower weight-for-age, weight-for-length z-scores and
      percentiles compared to normal birth weight infants according to CDC growth
      charts. CONCLUSIONS: Although low birth weight infants had lower anthropometric
      measures compared to a national reference population, they had significant catch
      up growth; High birth weight infants had significant slow-down growth. We suggest
      that growth assessments should compare infants' anthropometric data to their own
      previous growth measures as well as to a reference population. Further studies
      are needed to identify optimal ranges of infant weight gain.

PMID- 17006770
TI  - Prenatal programming of childhood overweight and obesity.
AB  - OBJECTIVE: To review the scientific evidence for prenatal programming of
      childhood overweight and obesity, and discuss its implications for MCH research,
      practice, and policy. METHODS: A systematic review of observational studies
      examining the relationship between prenatal exposures and childhood overweight
      and obesity was conducted using MOOSE guidelines. The review included literature
      posted on PubMed and MDConsult and published between January 1975 and December
      2005. Prenatal exposures to maternal diabetes, malnutrition, and cigarette
      smoking were examined, and primary study outcome was childhood overweight or
      obesity as measured by body mass index (BMI) for children ages 5 to 21. RESULTS:
      Four of six included studies of prenatal exposure to maternal diabetes found
      higher prevalence of childhood overweight or obesity among offspring of diabetic
      mothers, with the highest quality study reporting an odds ratio of adolescent
      overweight of 1.4 (95% CI 1.0-1.9). The Dutch famine study found that exposure to
      maternal malnutrition in early, but not late, gestation was associated with
      increased odds of childhood obesity (OR 1.9, 95% CI 1.5-2.4). All eight included
      studies of prenatal exposure to maternal smoking showed significantly increased
      odds of childhood overweight and obesity, with most odds ratios clustering around
      1.5 to 2.0. The biological mechanisms mediating these relationships are unknown
      but may be partially related to programming of insulin, leptin, and
      glucocorticoid resistance in utero. CONCLUSION: Our review supports prenatal
      programming of childhood overweight and obesity. MCH research, practice, and
      policy need to consider the prenatal period a window of opportunity for obesity
      prevention.

PMID- 17006773
TI  - Mobilizing residents for action: the role of small wins and strategic supports.
AB  - Yes we can! is a community-building initiative funded by the W. K. Kellogg
      Foundation that aims to improve educational and economic outcomes in Battle
      Creek, Michigan by mobilizing low-income communities and resident leaders and
      building their capacity to influence the decisions and policies that impact their
      lives. This paper describes the strategies pursued during the first phase of this
      initiative to foster resident mobilization by building small wins within the
      neighborhood. Primarily through a neighborhood-based mini-grant program and staff
      supports to encourage collective action, Yes we can! has started to increase
      levels of resident mobilization within the seven economically distressed
      neighborhoods that initially partnered with the W. K. Kellogg Foundation on this
      effort. The specific programming components and how they were implemented as well
      as the initial successes experienced are described. Lessons learned are
      discussed.

PMID- 17006772
TI  - Evaluating a program to build data capacity for core public health functions in
      local maternal child and adolescent health programs in california.
AB  - OBJECTIVES: To improve local Maternal and Child Health programs' capacity to
      collect and analyze data to support core public health functions, the California
      Maternal and Child Health Branch (CAMCHB) and the University of California San
      Francisco Family Health Outcomes project (FHOP) entered into a cooperative
      agreement. FHOP utilizes a 6-pronged strategy: face-to-face training, telephone
      technical assistance, on-site consultation, development of automated analytic
      tools, development of written guidelines, and web dissemination of data and
      materials. We evaluated the acceptability and effectiveness of these approaches.
      METHODS: Local Health Jurisdiction (LHJ) staff completed a self-administered
      questionnaire on use of and satisfaction with FHOP's services. A 34-item
      assessment tool was used to independently evaluate each 5-year community
      assessment plan submitted by LHJs to the CAMCHB. Administrative data on the use
      of FHOP's service was also considered. Correlational analyses were done to
      determine if use of FHOP services and materials was related to more adequate
      plans. RESULTS: LHJs with higher overall adequacy scores on their plans had an
      overall higher level of use of FHOP's products and services. LHJs with higher
      adequacy scores reported calling FHOP for technical assistance more frequently,
      using FHOP's book - "Developing an Effective Planning Process: A Guide for Local
      MCH Programs," and using FHOP's automated tools including EpiBC, an EpiINFO based
      program for birth certificate analysis, and Microsoft Excel data analysis
      templates. CONCLUSION: This 6-pronged strategy is well utilized and accepted by
      local MCH staff and appears to have some degree of association with better
      quality of local MCH plan documents.

PMID- 17006774
TI  - Organizational cultural competency: shifting programs for Latino immigrants from
      a client-centered to a community-based orientation.
AB  - This paper discusses how the organizational cultural competency of social service
      agencies may be improved by shifting the philosophy of service delivery from a
      client-centered to a community-based orientation. This analysis is based on two
      years of fieldwork and interviews that were conducted as part of an action
      research project initially developed to increase the number of certified Spanish
      speaking Latino family childcare providers and knowledge about Latino immigrant
      families in the Midwest. In developing a culturally-specific certification
      program in Spanish, both the Latino participants and the bilingual program
      director challenged the agency to consider how the social context and social
      location of its participants required a more holistic community approach.

PMID- 17006768
TI  - Emotion and pain: a functional cerebral systems integration.
AB  - Emotion and pain are psychological constructs that have received extensive
      attention in neuropsychological research. However, neuropsychological models of
      emotional processing have made more progress in describing how brain regions
      interact to process emotion. Theories of emotional processing can describe inter
      hemispheric and intra-hemispheric interactions during emotional processing. Due
      to similarities between emotion and pain, it is thought that emotional models can
      be applied to pain. The following review examines the neuropsychology of emotion
      and pain using a functional cerebral systems approach. Specific comparisons are
      made between pain and anger. Attention is given to differences in cerebral
      function and physiology that may contribute to the processing of emotion and
      pain. Suggestions for future research in emotion and pain are given.

PMID- 17006775
TI  - Abnormal use of facial information in high-functioning autism.
AB  - Altered visual exploration of faces likely contributes to social cognition
      deficits seen in autism. To investigate the relationship between face gaze and
      social cognition in autism, we measured both face gaze and how facial regions
      were actually used during emotion judgments from faces. Compared to IQ-matched
      healthy controls, nine high-functioning adults with autism failed to make use of
      information from the eye region of faces, instead relying primarily on
      information from the mouth. Face gaze accounted for the increased reliance on the
      mouth, and partially accounted for the deficit in using information from the
      eyes. These findings provide a novel quantitative assessment of how people with
      autism utilize information in faces when making social judgments.

PMID- 17006776
TI  - Longitudinal relationships between sibling behavioral adjustment and behavior
      problems of children with developmental disabilities.
AB  - Siblings of children with developmental disabilities were assessed twice, 2 years
      apart (N = 75 at Time 1, N = 56 at Time 2). Behavioral adjustment of the siblings
      and their brother or sister with developmental disability was assessed.
      Comparisons of adjustment for siblings of children with autism, Down syndrome,
      and mixed etiology mental retardation failed to identify group differences.
      Regression analysis showed that the behavior problems of the child with
      developmental disability at Time 1, but not the change in their behavior over
      time, predicted sibling adjustment over 2 years. There was no evidence that this
      putative temporal relationship operated bidirectionally: sibling adjustment did
      not appear to be related to the behavior problems of the children with
      developmental disabilities over time.

PMID- 17006777
TI  - Brief report: visual-spatial deficit in a 16-year-old girl with maternally
      derived duplication of proximal 15q.
AB  - Duplications of chromosome 15 may be one of the most common single genetic causes
      of autism spectrum disorders (ASD), aside from fragile X. Most of the cases are
      associated with maternally derived interstitial duplication involving 15q11-13.
      This case report describes a female proband with a maternally derived
      interstitial duplication of proximal 15q. She did not exhibit any symptoms of ASD
      apart from some developmental delay. By adolescence, she showed mild dysmorphism,
      a discrepant profile on the Wechsler Intelligence Scale for Children (Verbal IQ =
      87; Performance IQ = 65) and a major deficit in visual-spatial abilities
      affecting fine motor skills, mathematical reasoning, visual memory and some
      global reading tasks. This is one of the first reports of a child with a maternal
      duplication who exhibits a visual-spatial deficit without ASD.

PMID- 17006778
TI  - Improving the reliability of autism diagnoses: examining the utility of adaptive
      behavior.
AB  - The classification agreement of the Autism Diagnostic Interview-Revised (ADI-R)
      and the Autism Diagnostic Observation Schedule (ADOS) was examined in 129
      children and adolescents (aged 7-18 years) who were evaluated for autism.
      Participants received a diagnosis of autism or non-autism based on the ADI-R.
      Linear discriminant analysis revealed adequate concordance between the ADI-R and
      ADOS, with 75% of the participants being correctly classified using the ADOS.
      Classification accuracy significantly improved to 84% when a measure of adaptive
      functioning (i.e., the Vineland Adaptive Behavior Scales) was included in the
      analysis. The findings suggest that when clinicians obtain discrepant information
      on the ADI-R and ADOS, assessment of an individual's adaptive functioning may
      reduce diagnostic errors.

PMID- 17006780
TI  - The effects of PECS teaching to Phase III on the communicative interactions
      between children with autism and their teachers.
AB  - The study investigated the impact of mastery of the Picture Exchange
      Communication System (PECS) to Phase III, on the communications of children with
      autism. Children aged between 3 and 7 years, formed a PECS intervention group and
      a non-intervention control group. The intervention group received 15 h of PECS
      teaching over 5 weeks. Three 2-h classroom observations recorded communications
      between the children and their teachers. These occurred: 6 weeks before teaching;
      during the week immediately prior to teaching; during the week immediately
      following teaching. For the control group, two 2-h observations were separated by
      a 5-week interval without PECS teaching. Communicative initiations and dyadic
      interactions increased significantly between the children and teachers in the
      PECS group but not for the control group.

PMID- 17006787
TI  - [Benefits of a multimodular outpatient training program for patients with COPD].
AB  - BACKGROUND: The partition and chronological sequence of the different training
      items and modalities necessary for an effective training of patients with chronic
      obstructive pulmonary disease (COPD) remains a subject of debate. We investigated
      the combination of effective components of pulmonary rehabilitation in the
      settings outpatient lung sports group, home-based training and training in a gym.
      METHODS: Subjects were randomized to a 12-month training program and a no
      training group. PATIENTS AND MAIN RESULTS: The training group (n = 10, mean age:
      62.5 years, FEV1 53.4% predicted) reached an average increase in peakVO2 of 10%
      (p = 0.01) from 1.30 +/- 0.41 L/minute to 1.44 +/- 0.38 L/minute, in peak work
      rate of 14% (p = 0.007) from 82 +/- 39 W to 93 +/- 43 W and in the six-minute
      walking distance of 79 meters (p = 0.003), whereas in the control group (n = 9,
      mean age: 63.2 years, FEV1 53.7% predicted) no significant changes were observed.
      The quality of life obtained by use of the SF36-questionnaire and SGRQ also
      significantly improved in the training group, but not in the control group.
      CONCLUSION: This outpatient rehabilitation program is effective and appropriate
      for long-term rehabilitation of patients with COPD.

PMID- 17006788
TI  - [Pulmonary hamartoma--a rare cause of recurrent pneumonia in the course of
      immunosuppression].

PMID- 17006779
TI  - Characterization of an autism-associated segmental maternal heterodisomy of the
      chromosome 15q11-13 region.
AB  - Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome (PWS/AS) critical
      region have been described in individuals with autism. Maternal duplications and
      linkage disequilibrium in families with autism suggest the existence of a
      susceptibility locus at 15q11-q13. Here, we describe a 6-year-old girl diagnosed
      with autism, developmental delay, and delayed expressive and receptive language.
      The karyotype was designated de novo 47, XX, idic(15)(q13). Fluorescence in situ
      hybridization (FISH) and molecular analysis with 15q11-q13 markers revealed an
      additional copy of the region being of maternal origin. Duplication of the 15q11
      q13 segment represents the most consistent known chromosomal abnormality reported
      in association with autism. This present case report reinforces the hypothesis
      that additional copies of this chromosome segment are causally related to autism.

PMID- 17006789
TI  - [Quality of life in patients with home mechanical ventilation].
AB  - Health-related quality of life (HRQL) is defined as a psychological construct
      describing the subjectively experienced health status based on different
      components of health including physical state, psychological well-being, social
      relations and functional capacities. Assessment of HRQL has become steadily more
      essential in order to evaluate the costs and benefits of modern treatment
      modalities in patients with chronic and incurable diseases. This is particularly
      true for patients with home mechanical ventilation (HMV) and severe objective
      limitations in daily living. Modern instruments such as the Severe Respiratory
      Insufficiency (SRI) Questionnaire have been specifically designed for clinical
      trials which aim at assessing the effects of HMV on HRQL in these patients.
      Recent work has shown that mental health in clinically stable patients following
      establishment of HMV can be normal despite substantial physical handicaps.
      Further, HRQL has been shown to be predominantly influenced by the underlying
      disease. Accordingly, there is increasing evidence that HMV provides beneficial
      effects on HRQL in patients with neuromuscular and thoracic rib cage diseases,
      but in contrast, this remains still controversial in patients with COPD. Here,
      prospective controlled trials using modern specific instruments for HRQL
      assessment are required in the future to reliably evaluate the effects of HMV on
      HRQL in patients with COPD.

PMID- 17006790
TI  - [Diagnosis of community-acquired pneumonia].

PMID- 17006791
TI  - [Inhaled cyclosporin suppresses chronic projection following lung
      transplantation].

PMID- 17006792
TI  - [100th anniversary of the name DZK (German Central Committee against
      Tuberculosis)].

PMID- 17006793
TI  - [Endosonography in diagnosis and staging of lung cancer].
AB  - Today endosonography in form of endobronchial (EBUS) and endoesophageal
      ultrasound (EUS) is a routine adjunct to endoscopy in many pulmonary centers.
      Three different techniques are available and can improve the diagnosing and
      staging in patients with lung cancer. The clinical application and the diagnostic
      benefit have been established in a lot of studies compared with conventional
      radiologic methods and other diagnostic procedures. The role of endosonography is
      expected to grow in the near future as an important tool. Especially the
      approaches with EUS-fine needle aspiration (EUS-FNA) and/or EBUS controlled
      transbronchial needle aspiration (EBUS-TBNA) may be able to replace more invasive
      methods like mediastinoscopy for evaluating patients with lung cancer.

PMID- 17006794
TI  - [Sleep-related breathing disorders--a second edition of the International
      Classification of Sleep Disorders (ICSD-2) of the American Academy of Sleep
      Medicine (AASM)].
AB  - In 2005 the American Academy of Sleep Medicine (AASM) published a revised form of
      the International Classification of Sleep Disorders (ICSD-2). Goals of the ICSD-2
      are: A) To describe all currently recognized sleep and arousal disorders, and to
      base the descriptions on scientific and clinical evidence. B) To present the
      sleep and arousal disorders in an overall structure that is rational and
      scientifically valid. C) To render the sleep and arousal disorders as compatible
      with ICD-9 and ICD-10 as possible. In this article, sleep-disordered breathing
      disorders, as classified in the ICSD-2 are presented.

PMID- 17006795
TI  - [Recommendations on spirometry by Deutsche Atemwegsliga].

PMID- 17006796
TI  - Plasticity of photoprotective mechanisms of Buxus sempervirens L. leaves in
      response to extreme temperatures.
AB  - Summer 2003 was unusually hot in Western Europe, with local droughts and an
      intense heatwave, that led to a massive damage in vegetation. Since high
      temperatures are supposed to generate photooxidative stress, we analysed
      photoprotective responses in leaves of the evergreen boxtree (Buxus sempervirens
      L.) during summer 2003. All the photoprotective compounds analysed (alpha
      tocopherol, beta-carotene, and xanthophylls cycle pigments) were simultaneously
      induced in parallel with a reduction in photochemical efficiency (Fv/Fm). To
      characterise these responses, we compared these data with other data obtained
      during cold stress periods (2003, 2005) and with an unstressful summer (2002).
      Photoprotective responses observed during the heatwave were also induced by low
      temperature stress, and in both situations, this effect was exacerbated by light.
      In parallel with such induction the accumulation of red retro-carotenoids and
      xanthophyll esters was also observed under unfavourable conditions, suggesting a
      photoprotective role for both groups of carotenoids. This is the first report
      showing that in any species (Buxus sempervirens L.), the same retro-carotenoids
      can be induced in response to winter and summer stress. Present results
      demonstrate that the same mechanisms are induced as response to sub- and
      supraoptimal temperatures and the plasticity of such responses plays a critical
      role in plant acclimation to extreme temperatures, an ability that is specially
      important in the context of any future climate warming.

PMID- 17006797
TI  - Genetic diversity of Picea asperata populations based on RAPDs.
AB  - The genetic diversity of ten natural populations of Picea asperata Mast. were
      studied using RAPD markers. A total of 160 reproducible fragments were produced
      from the ten primers used. The mean number of fragments detected per individual
      was 114.7. Altogether 120 fragments were polymorphic among the ten populations,
      none of them were found to be population-specific. Nei's expected heterozygosity
      (H (e)) ranged from 0.233 to 0.269, and the average was 0.247. The analysis of
      molecular variance revealed that the coefficient of gene differentiation among
      populations, based on F (ST) and the unbiased estimate PhiST, equaled 0.224 and
      0.290, respectively. Such high values indicate that there is significant
      differentiation among populations, which could result from several factors,
      including restricted gene flow between populations (Nm = 0.866). Founder events
      may be another factor attributing to the high level of genetic differentiation.
      In addition, it was discovered that the geographic distribution is not correlated
      with the genetic distances among the populations of P. asperata.

PMID- 17006798
TI  - Designing and transgenic expression of melanin gene in tobacco trichome and
      cotton fiber.
AB  - In Streptomyces antibioticus, there are two genes TYRA and ORF438 required for
      the melanin biogenesis. To investigate whether expression of these two genes in
      cotton can change cotton fiber colour, we modified the TYRA and ORF438 genes to
      make their codon usage closer to the codon preference of cotton fiber genes. The
      resulting versions of these two genes were referred to as DTYRA and DORF438,
      respectively. Vacuolar targeting signals were also added to their ends. Under the
      cotton fiber specific LTP3 promoter, DORF438 and DTYRA were first transformed
      into model plant tobacco (Nicotiana tabacum). Molecular analyses showed that both
      the DORF438 and DTYRA genes were successfully expressed in transgenic plants, and
      the melanin deposition was observed in the trichomes of transgenic tobacco.
      Excitedly, when the same DORF438 and DTYRA expression cassettes were transformed
      into cotton (Gossypium hirsutum L.) by pollen tube pathway, the colour of cotton
      fiber changed from white to brown. Molecular analyses confirmed that both genes
      were transformed into cotton and expressed successfully. All these results
      indicate that the synthesized DOFR438 and DTYRA genes can work well in tobacco
      and cotton. Our study may provide a potential method for modifying the colour of
      cotton fiber.

PMID- 17006799
TI  - Subcellular effects of drought stress in Rosmarinus officinalis.
AB  - The use of Rosmarinus officinalis, and other wild plant species, in the
      Mediterranean area is an interesting solution in order to avoid the
      desertification and rapid soil erosion, because of their good resistance to
      environmental conditions. Previous articles have described experiments designed
      to determine the impact of water stress at the plant level in this species, but
      more knowledge is required at the subcellular and ultrastructural levels. An
      anatomic and ultrastructural study of the leaves was conducted on Rosmarinus
      officinalis plants growing under different water treatments. In the leaves of
      water-stressed plants, the leaf water potential and turgor decreased, and leaf
      osmotic potential became more negative with respect to control plants. The
      anatomic investigations showed that both the mesophyll intercellular spaces and
      the epidermal cell size were reduced significantly under the more intense drought
      stress conditions. At the subcellular level, chloroplasts accumulated
      plastoglobuli and lipid bodies, and cuticle thickness was increased under water
      stress. In our experiment, the anatomic and ultrastructural modifications of
      Rosmarinus officinalis could be considered an additional adaptation to drought
      stress together with physiological and biochemical modifications as antioxidant
      accumulation.

PMID- 17006801
TI  - Changes in the community of ectomycorrhizal fungi and increased fine root number
      under adult beech trees chronically fumigated with double ambient ozone
      concentration.
AB  - Forest soils are an important but under-studied part of forest ecosystems. The
      effects of O(3) on below-ground processes in a mature forest have only received
      limited attention so far. In our study, we have analysed the community of
      ectomycorrhizal fungi and beech fine root dynamics over two growing seasons (2003
      - 2004) in a 70-year old mixed spruce-beech forest stand, in which two groups of
      five adult beech trees were either fumigated by 2 x ambient ozone concentration
      or used as control. The main difference between previous studies and our approach
      was that previous studies were performed on seedlings in pot experiments or in
      closed or open top chambers, and not IN SITU, in a mature forest stand. Although
      beech is a relatively unresponsive species to tropospheric O(3), we found a
      pronounced effect of 2 x O(3) on the number of vital ectomycorrhizal root tips
      and non-turgescent fine roots. Both categories of roots were significantly
      increased when compared to controls in two consecutive years at each sampling
      event. The number of types of ectomycorrhizae and species richness increased in
      2004, but not in the extremely dry year 2003. We hypothesised that the observed
      changes might be an expression of a transitional state in below-ground succession
      of niches caused by an O(3) induced effect on carbon allocation to roots and the
      rhizosphere. We have detected changes in ectomycorrhizal species level, however
      Shannon-Weavers species diversity index and percentage of types of
      ectomycorrhizae did not change significantly in any sampling year thus indicating
      our results cannot be unequivocally explained by summer drought in year 2003 or
      by O(3) exposure alone.

PMID- 17006800
TI  - Structural-functional changes in detached cucumber leaves, and modelling these by
      hormone-treated leaf discs.
AB  - Senescence and rejuvenation were investigated in detached cucumber (Cucumis
      sativus L.) leaves after cultivation in nutrient solution for one week or four
      weeks. Rooting of the petiole (visible generally from the 7th day) elicited a
      combination of different morphological, anatomical, and physiological changes in
      the lamina. Extensive growth in area and thickness, extreme regreening, changes
      of chloroplast structure and activity, as well as the pattern of Chl-protein
      complexes were observed and compared either to the corresponding parameters of
      young detached leaves or mature attached leaves. These responses could be
      provoked separately by treating excised leaf discs with kinetin, benzyladenine,
      or indolylacetic acid. The hormones showed mutuality in their effects,
      benzyladenine being responsible for the growth of cells, while indolylacetic acid
      and kinetin promoted an increase in chlorophyll content. However, none of the
      treatments resulted in the growth of the chloroplasts in the leaf discs, which
      was only prominent in the rooting leaves.

PMID- 17006802
TI  - Effect of hydration state on testosterone and cortisol responses to training
      intensity exercise in collegiate runners.
AB  - Exercise intensity powerfully influences testosterone, cortisol, and testosterone
      : cortisol ratio (T:C) responses to endurance exercise. Hydration state may also
      modulate these hormones, and therefore may alter the anabolic/catabolic balance
      in response to endurance exercise and training. This study examined the effect of
      running intensity on testosterone, cortisol, and T : C when exercise was
      initiated in a hypohydrated state. Nine male collegiate runners (age = 20 +/- 0
      y, height = 178 +/- 2 cm, mass = 67.0 +/- 1.8 kg, body fat % = 9.8 +/- 0.7 %,
      V.O2max = 65.7 +/- 1.1 ml.kg (-1).min (-1)) completed four 10-min treadmill runs
      differing in pre-exercise hydration status (euhydrated, or hypohydrated by 5 % of
      body mass) and exercise intensity (70 % or 85 % V.O2max). Body mass, urine
      osmolality, and urine-specific gravity documented fluid balance; blood samples
      drawn pre-, immediately post-, and 20 min post-exercise were analyzed for
      testosterone, cortisol, and T : C. Except for heart rate measured during the 70 %
      V.O2max trials, heart rate, V.O2, and plasma lactate were similar between
      euhydrated and hypohydrated conditions for a given intensity, suggesting
      hypohydration did not measurably increase the physiological stress of the
      exercise bouts. Furthermore, hydration state had no measurable effect on
      testosterone concentrations before, during, or after exercise at either
      intensity. Regardless of exercise intensity, cortisol concentrations were greater
      during hypohydration than euhydration pre-exercise and 20 min post-exercise.
      Additionally, T : C was significantly lower 20 min post-exercise at 70 % V.O2max
      when subjects were initially hypohydrated (T : C = 0.055) versus euhydrated (T :
      C = 0.072). These findings suggest that depending on exercise intensity, T : C
      may be altered by hydration state, therefore influencing the balance between
      anabolism and catabolism in response to running exercise performed at typical
      training intensities.

PMID- 17006803
TI  - Evaluation of the energy cost of playing a dance simulation video game in
      overweight and non-overweight children and adolescents.
AB  - The purpose of this study was to determine if there were any differences in the
      submaximal energy cost of movement between overweight (OW) and non-overweight
      (NO) children while playing a dance simulation video game, Dance Dance Revolution
      (DDR) and to determine if the cardiorespiratory measures obtained while playing
      the game met the American College of Sports Medicine (ACSM) recommendations for
      developing and maintaining cardiorespiratory fitness. Twenty-two children and
      adolescents (10 OW vs. 12 NO) participated in the study. Cardiorespiratory
      measurements were taken both during a maximal treadmill walking test and during a
      12-minute Dance Dance Revolution protocol. The average absolute VO2 (OW: 917.1 +/
      257.1 vs. 590.6 +/- 147.9 mL . min (-1)) sustained over the DDR protocol was
      significantly higher in the OW group compared to the NO group. There was no
      significant difference in the average energy cost of movement when VO2 was
      normalized to fat-free mass (OW: 17.7 +/- 5.1 vs. NO: 17.3 +/- 3.9 mL . kgFFM (
      1) . min (-1)). Both groups were above the minimal ACSM recommended heart rate
      intensity for developing and maintaining cardiorespiratory fitness when
      participating in the DDR protocol (OW: 64.83 % +/- 7.14 vs. NO: 64.51 % +/-
      7.71), VO2 reserve, however, did not meet ACSM standards for developing and
      maintaining cardiorespiratory fitness.

PMID- 17006804
TI  - Doing the right thing (and figuring out what that is).

PMID- 17006805
TI  - Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA)
      decreases the incidence of MRSA bacteremia.
AB  - OBJECTIVES: To evaluate the influence of performance of active surveillance
      cultures for methicillin-resistant Staphylococcus aureus (MRSA) on the incidence
      of nosocomial MRSA bacteremia in an endemic hospital. DESIGN: Before-after trial.
      SETTING: A 700-bed hospital. PATIENTS: All patients admitted to the hospital who
      were at high risk for MRSA bacteremia. INTERVENTION: Performance of surveillance
      cultures for detection of MRSA were recommended for all patients at high risk,
      and contact isolation was implemented for patients with positive results of
      culture. Each MRSA-positive patient received one course of eradication treatment.
      We compared the total number of surveillance cultures, the percentage of
      surveillance cultures with positive results, and the number of MRSA bacteremia
      cases before the intervention (from January 2002 through February 2003) after the
      start of the intervention (from July 2003 through October 2004). RESULTS: The
      number of surveillance cultures performed increased from a mean of 272.57
      cultures/month before the intervention to 865.83 cultures/month after the
      intervention. The percentage of surveillance cultures with positive results
      increased from 3.13% before to 5.22% after the intervention (P < .001). The mean
      number of MRSA bacteremia cases per month decreased from 3.6 cases before the
      intervention to 1.8 cases after the intervention (P < 0.001). CONCLUSIONS: Active
      surveillance culture is important for identifying hidden reservoirs of MRSA.
      Contact isolation can prevent new colonization and infection and lead to a
      significant reduction of morbidity and healthcare costs.

PMID- 17006806
TI  - Active screening in high-risk units is an effective and cost-avoidant method to
      reduce the rate of methicillin-resistant Staphylococcus aureus infection in the
      hospital.
AB  - OBJECTIVE: To evaluate the impact of active screening for methicillin-resistant
      Staphylococcus aureus (MRSA) on MRSA infection rates and cost avoidance in units
      where the risk of MRSA transmission is high. METHODS: During a 15-month period,
      all patients admitted to our adult medical and surgical intensive care units
      (ICUs) were screened for MRSA nasal carriage on admission and weekly thereafter.
      The overall rates of all MRSA infections and of nosocomial MRSA infection in the
      2 adult ICUs and the general wards were compared with rates during the 15-month
      period prior to the start of routine screening. The percentage of patients
      colonized or infected with MRSA on admission and the cost avoidance of the
      surveillance program were also assessed. RESULTS: The overall rate of MRSA
      infections for all 3 areas combined decreased from 6.1 infections per 1,000
      census-days in the preintervention period to 4.1 infections per 1,000 census-days
      in the postintervention period (P = .01). The decrease remained statistically
      significant when only nosocomial MRSA infections were examined (4.5 vs 2.8
      infections per 1,000 census-days; P < .01), despite a corresponding increase
      during the postintervention period in the percentage of patients with onset of
      MRSA infection in the first 72 hours after admission to the general wards (46% to
      81%; P < .005). A total of 3.7% of ICU patients were colonized or infected with
      MRSA on admission; MRSA would not have been detected in 91% of these patients if
      screening had not been performed. At a cost of Dollars 3,475/month for the
      program, we averted a mean of 2.5 MRSA infections/month for the ICUs combined,
      avoiding Dollars 19,714/month in excess cost in the ICUs. CONCLUSIONS: Even in a
      setting of increasing community-associated MRSA, active MRSA screening as part of
      a multi-factorial intervention targeted to high-risk units may be an effective
      and cost-avoidant strategy for achieving a sustained decrease of MRSA infections
      throughout the hospital.

PMID- 17006807
TI  - Impact of alcohol-based, waterless hand antiseptic on the incidence of infection
      and colonization with methicillin-resistant Staphylococcus aureus and vancomycin
      resistant enterococci.
AB  - OBJECTIVE: Colonized and infected inpatients are major reservoirs for methicillin
      resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci
      (VRE), and transient carriage of these pathogens on the hands of healthcare
      workers remains the most common mechanism of patient-to-patient transmission. We
      hypothesized that use of alcohol-based, waterless hand antiseptic would lower the
      incidence of colonization and/or infection with MRSA and VRE. METHODS: On June
      19, 2001, alcohol hand antiseptic was introduced at the University campus and not
      the nearby Memorial campus of the University of Massachusetts Medical School
      (Worcester, MA), allowing us to evaluate the impact of this antiseptic on the
      incidence of MRSA and VRE colonization and infection. From January 1 through
      December 31, 2001, the incidence of MRSA colonization or infection was compared
      between the 2 campuses before and after the hand antiseptic was introduced. Its
      effect on VRE colonization and infection was only studied in the medical
      intensive care unit at the University campus. RESULTS: At the University campus,
      the incidence of MRSA colonization or infection decreased from 1.26 cases/1,000
      patient-days before the intervention to 0.75 cases/1,000 patient-days after the
      intervention, for a 1.46-fold decrease (95% confidence interval, 1.04-2.58; P =
      .037). At the Memorial campus, the incidence of MRSA colonization or infection
      remained virtually unchanged, from 0.34 cases/1,000 patient-days to 0.49
      cases/1,000 patient-days during the same period. However, a separate analysis of
      the University campus data that controlled for proximity to prevalent cases did
      not show a significant improvement in the rates of infection or colonization. The
      incidence of nosocomial VRE colonization or infection before and after the hand
      antiseptic decreased from 12.0 cases/1,000 patient-days to 3.0 cases/1,000
      patient-days, a 2.25-fold decrease (P = .018). Compliance with rectal
      surveillance for detection of VRE was 86% before and 84% after implementation of
      the hand antiseptic intervention. The prevalences of VRE cases during these 2
      periods were 25% and 29%, respectively (P = .017). CONCLUSIONS: Alcohol hand
      antiseptic appears to be effective in controlling the transmission of VRE.
      However, after controlling for proximity to prevalent cases (ie, for clustering),
      it does not appear to be more effective than standard methods for controlling
      MRSA. Further controlled studies are needed to evaluate its effectiveness.

PMID- 17006808
TI  - Characteristics of patients with healthcare-associated infection due to SCCmec
      type IV methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) with the
      staphylococcal cassette chromosome mec (SCCmec) type IV allele is most commonly
      associated with community-acquired MRSA (CA-MRSA) infection; however, such
      organisms have also been identified in the healthcare setting. The objective of
      the present study was to characterize the epidemiology of and clinical outcomes
      associated with SCCmec-IV MRSA infection acquired in the healthcare setting,
      compared with infection caused by MRSA of other SCCmec types. DESIGN: We
      evaluated a cohort of 100 inpatients with MRSA infection that met the Centers for
      Disease Control and Prevention definition for healthcare-associated infection and
      compared the patients' demographic characteristics, the antimicrobial
      susceptibilities of the MRSA isolates, the infection types, and the associated
      clinical and microbiological outcomes. For each MRSA isolate, the SCCmec type and
      the presence of Panton-Valentine leukocidin (PVL) were determined by polymerase
      chain reaction methods. RESULTS: SCCmec-IV MRSA isolates were isolated from 53
      patients (42% of these isolates were positive for PVL), and SCCmec-II or SCCmec
      III MRSA was isolated from 47 patients (3% of these isolates were positive for
      PVL). No differences were noted between the patients in the SCCmec-II/III group
      and the patients in the SCCmec-IV group with respect to age (median, 55 vs 50
      years); sex (77% vs 64% of patients were male); medical service (surgical
      service, 60% in both groups; ICU admission, 55% vs 53%), Acute Physiology and
      Chronic Health Evaluation II score (median, 8 vs. 7); infection type; or
      underlying comorbidities, except for presence of a burn wound (13% vs 2%; P <
      .04). Patients in the SCCmec-II/III group were more likely to have multiple sites
      of infection (P = .006) and a longer length of stay (LOS) prior to detection of
      MRSA than were patients in the SCCmec-IV group (median, 4 vs 1 days; P < .001).
      Total LOS was significantly greater for patients in the SCCmec-II/III, compared
      with those in the SCCmec-IV group (P = .006). Multiple logistic regression
      identified liver disease and longer LOS prior to detection of MRSA as predictors
      of infection with SCCmec-II/III MRSA. Rates of susceptibility to clindamycin,
      gentamicin, ciprofloxacin, levofloxacin, and tetracycline was significantly
      greater among SCCmec-IV MRSA isolates, compared with type II/III isolates (P < or
      = .05). Compared with SCCmec-IV isolates acquired in the community, the
      susceptibility rates among healthcare-associated SCCmec-IV isolates was
      significantly less for clindamycin, gentamicin, and levofloxacin, indicating that
      these organisms may quickly acquire resistance to non- beta -lactam antibiotics,
      as do SCCmec-II/III strains. CONCLUSIONS: SCCmec-IV MRSA appears to have become
      established in hospitals. The onset of infection caused by SCCmec-IV strains is
      earlier than the onset of infection with SCCmec-II/III strains; however,
      associated types of infection are similar. Infection with SCCmec-II/III MRSA is
      currently associated with an adverse impact on outcome, compared with infection
      with SCCmec-IV MRSA. Further research is warranted to determine the impact of
      SCCmec type IV strains in hospital settings.

PMID- 17006809
TI  - Epidemiology of methicillin-resistant Staphylococcus aureus colonization in a
      surgical intensive care unit.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of
      healthcare-associated infections among surgical intensive care unit (ICU)
      patients, though transmission dynamics are unclear. OBJECTIVE: To determine the
      prevalence of MRSA nasal colonization at ICU admission, to identify associated
      independent risk factors, to determine the value of these factors in active
      surveillance, and to determine the incidence of and risk factors associated with
      MRSA acquisition. DESIGN: Prospective cohort study. SETTING: Surgical ICU at a
      teaching hospital. PATIENTS: All patients admitted to the surgical ICU. RESULTS:
      Active surveillance for MRSA by nasal culture was performed at ICU admission
      during a 15-month period. Patients who stayed in the ICU for more than 48 hours
      had nasal cultures performed weekly and at discharge from the ICU, and clinical
      data were collected prospectively. Of 1,469 patients, 122 (8%) were colonized
      with MRSA at admission; 75 (61%) were identified by surveillance alone. Among 775
      patients who stayed in the ICU for more than 48 hours, risk factors for MRSA
      colonization at admission included the following: hospital admission in the past
      year (1-2 admissions: adjusted odds ratio [aOR], 2.60 [95% confidence interval
      {CI}, 1.47-4.60]; more than 2 admissions: aOR, 3.56 [95% CI, 1.72-7.40]), a
      hospital stay of 5 days or more prior to ICU admission (aOR, 2.54 [95% CI, 1.49
      4.32]), chronic obstructive pulmonary disease (aOR, 2.16 [95% CI, 1.17-3.96]),
      diabetes mellitus (aOR, 1.87 [95% CI, 1.10-3.19]), and isolation of MRSA in the
      past 6 months (aOR, 8.18 [95% CI, 3.38-19.79]). Sixty-nine (10%) of 670 initially
      MRSA-negative patients acquired MRSA in the ICU (corresponding to 10.7 cases per
      1,000 ICU-days at risk). Risk factors for MRSA acquisition included tracheostomy
      in the ICU (aOR, 2.18 [95% CI, 1.13-4.20]); decubitus ulcer (aOR, 1.72 [95% CI,
      0.97-3.06]), and receipt of enteral nutrition via nasoenteric tube (aOR, 3.73
      [95% CI, 1.86-7.51]), percutaneous tube (aOR, 2.35 [95% CI, 0.74-7.49]), or both
      (aOR, 3.33 [95% CI, 1.13-9.77]). CONCLUSIONS: Active surveillance detected a
      sizable proportion of MRSA-colonized patients not identified by clinical culture.
      MRSA colonization on admission was associated with recent healthcare contact and
      underlying disease. Acquisition was associated with potentially modifiable
      processes of care.

PMID- 17006810
TI  - Molecular characterization of methicillin-resistant Staphylococcus aureus
      disseminated in a home care system.
AB  - OBJECTIVE: To study colonization with methicillin-resistant Staphylococcus aureus
      in a home care service during a 4-month period. DESIGN: Prospective study.
      SETTING: A home care service located in Rio de Janeiro, Brazil. PARTICIPANTS:
      Patients admitted to the home care service during this period, their household
      contacts, and health care workers (HCWs). METHODS: Swab specimens from the
      anterior nares were collected from each patient in the 3 groups at admission.
      Screening was repeated every 7 days. MRSA was detected using a mecA probe, and
      the clonality of isolates was evaluated by molecular methods, primarily pulsed
      field gel electrophoresis. RESULTS: Of the 59 study patients, 9 (15.3%) had MRSA
      colonization detected; these cases of colonization were classified as imported.
      Only 1 (2.0%) of the 50 patients not colonized at admission became an MRSA
      carrier (this case of colonization was classified as autochthonous). Two (0.9%)
      of 224 household contacts and 16 (7.4%) of 217 HCWs had MRSA colonization. Cross
      transmission from patient to HCW could be clearly demonstrated in 8 cases. The
      great majority of MRSA isolates belonged to the Brazilian epidemic clone.
      CONCLUSIONS: MRSA colonization was common in the home care service analyzed. The
      fact that the majority of MRSA isolates obtained were primarily of nosocomial
      origin (and belonged to the so-called Brazilian epidemic clone) substantiated our
      findings that all but 1 patient had already been colonized before admission to
      the home care service. Only cross-transmission from patients to healthcare
      workers could be verified. On the basis of these results, we believe that a
      control program built on admission screening of patients for detection of MRSA
      carriage could contribute to the overall quality of care.

PMID- 17006812
TI  - Emergence of community-associated methicillin-resistant Staphylococcus aureus
      infection among patients with end-stage renal disease.
AB  - OBJECTIVE: To evaluate the frequency of infections due to community-associated
      methicillin-resistant Staphylococcus aureus (CA-MRSA) strains among our patients
      with end-stage renal disease. DESIGN: Prospective observational clinical and
      laboratory study of patients in 2005. Molecular features of isolates recovered
      from these patients were compared with those of isolates recovered in 2000 from
      patients with end-stage renal disease. SETTING: A 600-bed urban academic medical
      center. PATIENTS: Thirty-two patients with end-stage renal disease and MRSA
      infection at the time of hospitalization from 2005 were evaluated. For
      comparison, laboratory analysis was performed for 17 MRSA isolates recovered from
      patients with end-stage renal disease in 2000. RESULTS: The patients from 2005
      were more likely than the patients from 2000 to have infection with strains that
      carried the staphylococcal cassette chromosome (SCC) mec type IV complex (50% vs
      11.8%; relative risk, 4.25 [95% confidence interval, 1.17-25.98]; P = .012) and
      the Panton-Valentine leukocidin toxin genes (25% vs 0%; P = .038). Eight patients
      from 2005 were infected with a strain that is identical to MRSA clone USA300 in
      terms of molecular type and presence of SCCmec type IV and Panton-Valentine
      leukocidin genes. Among the patients from 2005, those infected with SCCmec type
      IV strains (ie, CA-MRSA strains) and those infected with SCCmec type II strains
      (ie, healthcare-associated MRSA [HA-MRSA] strains) were similar with respect to
      demographic characteristics, risk factors, and outcomes. CONCLUSIONS: We
      documented an increased proportion of infections with CA-MRSA strains, including
      clone USA300, among our population of patients undergoing dialysis. Patients
      infected with CA-MRSA strains and HA-MRSA strains were similar with respect to
      presenting illness and outcomes.

PMID- 17006811
TI  - Community-associated strains of methicillin-resistant Staphylococccus aureus as
      the cause of healthcare-associated infection.
AB  - OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) isolates from
      patients with community-associated infection have been described as strains
      genetically distinct from the strains isolated from patients with healthcare
      associated infection. This study examines the hypothesis that community
      associated MRSA (CA-MRSA) strains now cause serious infections in hospitalized
      patients. METHODS: Thirty-seven clinical MRSA isolates were randomly selected
      from blood isolates obtained from July 2003 through June 2004. Strains were
      tested for staphylococcal chromosomal cassette mec (SCCmec) type, pulsed-field
      gel electrophoresis (PFGE) type, and presence of Panton-Valentine leukocidin
      (PVL) genes. Medical records review and epidemiologic classification was
      performed by an investigator blinded to the results of the bacterial strain
      analysis. Episodes of bloodstream infection were independently classified as
      either community-associated or healthcare-associated infections, and bacterial
      isolates were independently classified as either CA-MRSA strains or healthcare
      associated MRSA (HA-MRSA) strains, according to established definitions. SETTING:
      A tertiary care Veterans Affairs Medical Center. RESULTS: Twenty-four (65%) of 37
      MRSA isolates were SCCmec type IV, a genetic type characteristic of CA-MRSA
      strains; 22 of these 24 isolates belonged to the CA-MRSA clone USA300 and carried
      PVL genes. Thirteen (35%) of the 37 strains were SCCmec type II, of which 12 were
      USA100-ST5 and 12 lacked PVL genes. Thirty patients (81%) had healthcare
      associated infections; 18 (60%) of these 30 were infected with isolates carrying
      markers of CA-MRSA strains. Of 7 patients with CA-MRSA infections, 6 were
      infected with isolates belonging to the USA300 clone. Patients with healthcare
      associated bloodstream infections were as likely to be infected with a CA-MRSA
      strain as patients with a community-associated infection (P = .38). CONCLUSIONS:
      MRSA strains with molecular characteristics of CA-MRSA strains have emerged as an
      important cause of serious healthcare-associated infection in our hospital.

PMID- 17006813
TI  - Carriage of multiple subtypes of methicillin-resistant Staphylococcus aureus by
      intensive care unit patients.
AB  - OBJECTIVE: To determine how consistently patients are colonized with methicillin
      resistant Staphylococcus aureus (MRSA) at various sites and how many subtypes can
      be carried simultaneously by a single patient. SETTING: A 28-bed Intensive care
      unit in a tertiary-care referral hospital. METHODS: A total of 1,181 patients
      were screened by culture of swab specimens obtained from the nose, throat, groin,
      and axilla on admission to the intensive care unit (ICU), twice weekly during
      their ICU stay, and at discharge. RESULTS: MRSA was isolated at least once from
      224 patients. Of these isolates, 359 were selected from 32 patients to be
      subtyped using pulsed-field gel electrophoresis. The rate of compliance with
      collection of swab specimens was 79.9%. The combination of sites colonized varied
      frequently over time for many patients. Of patients who had swab specimens
      obtained twice in 1 day, 8.7% had discordant results from the 2 swab sets. No
      patient had a clinical isolate that was not of an identical subtype to an isolate
      from an anatomical site that was sampled for screening. Half the patients carried
      multiple subtypes during their stay, with up to 4 subtypes per patient.
      CONCLUSIONS: The findings of this study may indicate that these patients have
      been colonized with MRSA on more than one occasion, possibly because of multiple
      breaches in infection control procedure. In MRSA-colonized patients, anatomical
      sites were intermittently colonized and carriage of multiple subtypes was common.
      These findings indicate that MRSA carriage is not a fixed state but may vary over
      time.

PMID- 17006814
TI  - Surveillance for vancomycin-resistant enterococci: type, rates, costs, and
      implications.
AB  - OBJECTIVE: To evaluate 2 active surveillance strategies for detection of enteric
      vancomycin-resistant enterococci (VRE) in an intensive care unit (ICU). DESIGN:
      Thirty-month prospective observational study. SETTING: ICU at a university
      affiliated referral center. PATIENTS: All patients with an ICU stay of 24 hours
      or more were eligible for the study. INTERVENTION: Clinical active surveillance
      (CAS), involving culture of a rectal swab specimen for detection of VRE, was
      performed on admission, weekly while the patient was in the ICU, and at
      discharge. Laboratory-based active surveillance (LAS), involving culture of a
      stool specimen for detection of VRE, was performed on stool samples submitted for
      Clostridium difficile toxin detection. RESULTS: Enteric colonization with VRE was
      detected in 309 (17%) of 1,872 patients. The CAS method initially detected 280
      (91%) of the 309 patients colonized with VRE, compared with 25 patients (8%)
      detected by LAS; colonization in 4 patients (1%) was initially detected by
      analysis of other clinical specimens. Most patients with colonization (76%) would
      have gone undetected by LAS alone, whereas use of the CAS method exclusively
      would have missed only 3 patients (1%) who were colonized. CAS cost Dollars 1,913
      per month, or Dollars 57,395 for the 30-month study period. Cost savings of CAS
      from preventing cases of VRE colonization and bacteremia were estimated to range
      from Dollars 56,258 to Dollars 303,334 per month. CONCLUSIONS: A patient-based
      CAS strategy for detection of enteric colonization with VRE was superior to LAS.
      In this high-risk setting, CAS appeared to be the most efficient and cost
      effective surveillance method. The modest costs of CAS were offset by the averted
      costs associated with the prevention of VRE colonization and bacteremia.

PMID- 17006815
TI  - Molecular characterization of vancomycin-resistant enterococci from clinical and
      surveillance specimens.
AB  - OBJECTIVE: To compare the molecular characteristics of infection-derived (ID)
      isolates and intestinal colonization-derived (ICD) isolates of vancomycin
      resistant enterococci (VRE) recovered from hospitalized patients. DESIGN: A 12
      month prospective cohort study. SETTING: A 1,000-bed teaching facility. METHODS:
      From January through December 2004, a total of 30 pairs of vanA-containing
      enterococcal isolates were collected from patients admitted to a teaching
      hospital in South Korea. Each pair comprised an ID and an ICD VRE isolate from
      the same patient. All VRE isolates were investigated on the basis of SmaI
      restricted pulsed-field gel electrophoresis (PFGE) pattern, Tn1546 type, and
      presence of the esp gene, including A and C repeat number variation. RESULTS:
      Members of 19 pairs (63%) of VRE isolates were genetically indistinguishable from
      each other. The 11 patients for whom the molecular characteristics of the ID
      isolates differed from those of the ICD isolates had longer durations of
      hospitalization and intensive care unit (ICU) stay, compared with the other 19
      patients. CONCLUSIONS: These findings suggest the longer durations of
      hospitalization and ICU stay may be possible risk factors for colonization with
      multiple clones of VRE.

PMID- 17006816
TI  - Role of horizontal transfer of the transposon Tn1546 in the nosocomial spread of
      vanA vancomycin-resistant enterococci at a tertiary care hospital in Korea.
AB  - OBJECTIVE: To investigate the epidemiologic characteristics of vancomycin
      resistant enterococci (VRE) infection. DESIGN: An epidemiologic description by
      means of chromosomal DNA fingerprinting and transposon typing. SETTING: A 2,200
      bed tertiary care hospital in Korea. PATIENTS: First VRE isolates were obtained
      from patients hospitalized from April 1997 to December 2001. INTERVENTIONS: The
      van genotypes of isolates were identified by means of multiplex polymerase chain
      reaction (PCR). The macrorestriction patterns of chromosomal DNA were determined
      by pulsed-field gel electrophoresis (PFGE). The transposon Tn1546 was typed by
      means of 2 sets of long PCR restriction fragment-length polymorphism analysis,
      which were ClaI restriction of a 10.4-kb region from orf1 to vanZ and DdeI
      restriction of a 4.4-kb region from vanR to vanX. RESULTS: VRE isolates were
      recovered from 215 patients. All were vanA genotype. PFGE analysis of the 215
      isolates showed 172 types, including 21 clusters composed of 64 isolates and 151
      types of as many isolates. Each type was composed of 2-10 isolates; the isolates
      within each PFGE cluster were detected within a 10-month period and mostly shared
      a transposon type. Transposon typing classified 169 strains into 15 types and 158
      strains belonged to 4 major transposon clusters. Each of these 4 transposon
      clusters was isolated from patients treated in 5-22 different wards during a 31
      52 month period and consisted of 9-80 PFGE types. Each of the other 11 types were
      found in only one strain. CONCLUSIONS: Our findings suggest that the horizontal
      transfer of Tn1546 has a major role in the nosocomial spread of vanA VRE. Clonal
      spread of VRE seemed to contribute to short-term dissemination in limited areas.

PMID- 17006817
TI  - Antimicrobial use control measures to prevent and control antimicrobial
      resistance in US hospitals.
AB  - OBJECTIVE: Clinical practice guidelines and recommended practices to control use
      of antibiotics have been published, but the effect of these practices on
      antimicrobial resistance (AMR) rates in hospitals is unknown. The objective of
      this study was to examine relationships between antimicrobial use control
      strategies and AMR rates in a national sample of US hospitals. DESIGN: Cross
      sectional, stratified study of a nationally representative sample of US
      hospitals. METHODS: A survey instrument was sent to the person responsible for
      infection control at a sample of 670 US hospitals. The outcome was current
      prevalences of 4 epidemiologically important, drug-resistant pathogens,
      considered concurrently: methicillin-resistant Staphylococcus aureus (MRSA),
      vancomycin-resistant enterococci, ceftazidime-resistant Klebsiella species, and
      quinolone (ciprofloxacin)-resistant Escherichia coli. Five independent variables
      regarding hospital practices were selected from the survey: the extent to which
      hospitals (1) implement practices recommended in clinical practice guidelines and
      ensure best practices for antimicrobial use, (2) disseminate information on
      clinical practice guidelines for antimicrobial use, (3) use antimicrobial-related
      information technology, (4) use decision support tools, and (5) communicate to
      prescribers about antimicrobial use. Control variables included the hospitals'
      number of beds, teaching status, Veterans Affairs status, geographic region, and
      number of long-term care beds; and the presence of an intensive care unit, a burn
      unit, or transplant services. A generalized estimating equation modeled all
      resistance rates simultaneously to identify overall predictors of AMR levels at
      the facility. RESULTS: Completed survey instruments were returned by 448
      hospitals (67%). Four antimicrobial control measures were associated with higher
      prevalence of AMR. Implementation of recommended practices for antimicrobial use
      (P < .01) and optimization of the duration of empirical antibiotic prophylaxis (P
      < .01) were associated with a lower prevalence of AMR. Use of restrictive
      formularies (P = .05) and dissemination of clinical practice guideline
      information (P < .01) were associated with higher prevalence of AMR. Number of
      beds and Veterans Affairs status were also associated with higher AMR rates
      overall. CONCLUSIONS: Implementation of guideline-recommended practices to
      control antimicrobial use and optimize the duration of empirical therapy appears
      to help control AMR rates in US hospitals. A longitudinal study would confirm the
      results of this cross-sectional study. These results highlight the need for
      systems interventions and reengineering to ensure more-consistent application of
      guideline-recommended measures for antimicrobial use.

PMID- 17006818
TI  - What to think if the results of the National Institutes of Health randomized
      trial of methicillin-resistant Staphylococcus aureus and vancomycin-resistant
      enterococcus control measures are negative (and other advice to young
      epidemiologists): a review and an au revoir.
AB  - The incidence of methicillin-resistant Staphylococcus aureus (MRSA) and
      vancomycin-resistant Enterococcus (VRE) infections continues to rise in National
      Nosocomial Infections Surveillance system hospitals, and these pathogens are
      reportedly causing more than 100,000 infections and many deaths each year in US
      healthcare facilities. This has led some to insist that control measures are now
      urgently needed, but several recent articles have suggested that isolation of
      patients does not work, is not needed, or is unsafe, or that a single cluster
      randomized trial could be used to decide such matters. At least 101 studies have
      reported controlling MRSA infection and 38 have reported controlling VRE
      infection by means of active detection by surveillance culture and use of
      isolation for all colonized patients in healthcare settings where the pathogens
      are epidemic or endemic, in academic and nonacademic hospitals, and in acute
      care, intensive care, and long-term care settings. MRSA colonization and
      infection have been controlled to exceedingly low levels in multiple nations and
      in the state of Western Australia for decades by use of active detection and
      isolation. Studies suggesting problems with using such data to control MRSA
      colonization and infection have their own problems, which are discussed.
      Randomized trials are epidemiologic tools that can sometimes provide erroneous
      results, and they have not been considered necessary for studying isolation
      before it is used to control other important infections, such as tuberculosis,
      smallpox, and severe acute respiratory syndrome. No single epidemiologic study
      should be considered definitive. One should always weigh all available evidence.
      Infection with antibiotic-resistant pathogens such as MRSA and VRE is
      controllable to a low level by active detection and isolation of colonized and
      infected patients. Effective measures should be used to minimize the morbidity
      and mortality attributable to these largely preventable infections.

PMID- 17006819
TI  - Use of germicides in the home and the healthcare setting: is there a relationship
      between germicide use and antibiotic resistance?
AB  - BACKGROUND: The spread of antibiotic-resistant pathogens represents an increasing
      threat in healthcare facilities. Concern has been expressed that the use of
      surface disinfectants and antiseptics may select for antibiotic-resistant
      pathogens. OBJECTIVE: To review the scientific literature on whether there is a
      link between use of germicides (ie, disinfectants and antiseptics) and bacterial
      resistance to antibiotics. In addition, we will review whether antibiotic
      resistant bacteria exhibit altered susceptibility to germicides that are
      recommended for use as disinfectants or antiseptics. DESIGN: A review of the
      appropriate scientific literature. RESULTS: In the laboratory, it has been
      possible to develop bacterial mutants with reduced susceptibility to
      disinfectants and antiseptics that also demonstrate decreased susceptibility to
      antibiotics. However, the antibiotic resistance described was not clinically
      relevant because the test organism was rarely a human pathogen, the altered level
      of antimicrobial susceptibility was within achievable serum levels for the
      antibiotic, or the antibiotic tested was not clinically used to treat the study
      pathogen. Similarly, wild-type strains with reduced susceptibility to
      disinfectants (principally, quaternary ammonium compounds) and antiseptics
      (principally, triclosan) have been reported. However, because the concentration
      of disinfectants used in the healthcare setting greatly exceeds the concentration
      required to kill strains with reduced susceptibility to disinfectants, the
      clinical relevance of these observations is questionable. CONCLUSION: To date,
      there is no evidence that using recommended antiseptics or disinfectants selects
      for antibiotic-resistant organisms in nature. Disinfectants and antiseptics
      should be used when there are scientific studies demonstrating benefit or when
      there is a strong theoretical rationale for using germicides.

PMID- 17006820
TI  - Use of gaseous ozone for eradication of methicillin-resistant Staphylococcus
      aureus from the home environment of a colonized hospital employee.
AB  - An intensive care nurse with eczema was repeatedly treated for methicillin
      resistant Staphylococcus aureus (MRSA) carriage. Because cultures remained
      positive for MRSA, her house was investigated. Thirty-four percent of
      environmental samples yielded MRSA. Her children and cat were free of MRSA. The
      house was decontaminated with gaseous ozone. All subsequent cultures were
      negative for MRSA. This decontamination cost Euros 2,000 (approximately Dollars
      2,400).

PMID- 17006821
TI  - How often do asymptomatic healthcare workers cause methicillin-resistant
      Staphylococcus aureus outbreaks? A systematic evaluation.
AB  - A systematic search was performed to identify outbreaks of methicillin-resistant
      Staphylococcus aureus infection and colonization caused by healthcare workers
      (HCWs). Of 191 outbreaks identified, 11 had strong epidemiological evidence that
      HCWs were the source. In 3 of these outbreaks, asymptomatic carriers were the
      cause. The frequent practice of screening asymptomatic HCWs should be
      reconsidered.

PMID- 17006822
TI  - Association between hand hygiene compliance and methicillin-resistant
      Staphylococcus aureus prevalence in a French rehabilitation hospital.
AB  - We simultaneously investigated the prevalence of methicillin-resistant
      Staphylococcus aureus (MRSA) and compliance with hand hygiene in the clinical
      wards of a French rehabilitation hospital. We found that the rate of hand hygiene
      compliance observed at the patient's bedside was a strong predictor of MRSA
      prevalence.

PMID- 17006823
TI  - The decrease in healthcare-associated methicillin-resistant Staphylococcus aureus
      infections and savings from glycopeptide use.
AB  - We evaluated changes in the rate of healthcare-associated methicillin-resistant
      Staphylococcus aureus (MRSA) infections and healthcare-associated S. aureus
      infections after implementation of infection control precautions and the effect
      of this on glycopeptide use and expenditures for glycopeptides in a private
      medical center in Turkey in the years 2000-2005. A striking decrease was obtained
      in the number of MRSA infections, and the expenditure for glycopeptide use also
      decreased.

PMID- 17006824
TI  - Epidemiology of community-acquired methicillin-resistant Staphylococcus aureus
      skin infections among healthcare workers in an outpatient clinic.
AB  - We describe an investigation of soft-tissue infections caused by community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strains in 2
      healthcare workers employed in an outpatient clinic for patients with human
      immunodeficiency virus infection. Cultures of environmental samples from multiple
      surfaces in the clinic grew toxin-producing CA-MRSA strains, suggesting fomites
      may play a role in the transmission of these strains of MRSA.

PMID- 17006825
TI  - Incidence and epidemiology of methicillin-resistant Staphylococcus aureus
      infection in a Saudi Arabian Hospital, 1999-2003.
AB  - During 1999-2003 in a Saudi Arabian Hospital, methicillin-resistant
      Staphylococcus aureus constituted 6% of all S. aureus isolates; the proportion
      had increased from 2% in 1999, to 9.7% in 2002, to 8% in 2003. Of all MRSA
      isolates, 62% represented community-acquired infection, 20.4% represented
      healthcare-associated infection, and 17.6% represented nosocomial infection. The
      proportion of community-acquired isolates increased from 41.7% in 1999 to 66.6%
      in 2002, and the proportion representing nosocomial infection decreased from 33%
      in 1999 to 19% in 2003. Isolates representing nosocomial infection showed higher
      rates of resistance to ciprofloxacin (76.6%), clindamycin (76.6%), erythromycin
      (68%) and trimethoprim-sulfamethoxazole (68%) than did isolates in the other
      categories (P<.001).

PMID- 17006826
TI  - Technical note: assay of cell quantity in the fibroblast-populated collagen
      matrix with a tetrazolium reagent.
AB  - Determination of cell quantity in three-dimensional culture systems, such as the
      fibroblast-populated collagen matrix, can be difficult secondary to the abundance
      of extracellular collagen. The WST-1 assay, which can quantitate cellular
      processes in monolayer culture, was tested as a measure of relative cell quantity
      in a three dimensional culture system, the fibroblast-populated collagen matrix.
      The assay had acceptable accuracy and precision, and was not affected by the
      extracellular matrix. It was concluded that the assay was a reasonable
      alternative to other measures of cell quantity in the fibroblast-populated
      collagen matrix.

PMID- 17006827
TI  - [Small lesions of the thyroid gland--the significance of ultrasound examination
      in the selection of lesions for biopsy].
AB  - INTRODUCTION: The aim of this study was to find the ultrasound (US) features
      which can be helpful in selecting small thyroid lesions for fine needle
      aspiration biopsy (FNAB). MATERIALS AND METHODS: The outcomes were analyzed of US
      examinations, FNABs, and postoperative histopathological examinations performed
      during the years 2000-2005. The occurrence of small lesions of the thyroid
      revealed by US was assessed. Then, palpability and several US features of those
      lesions were evaluated, like the total echogenicity, the pattern of
      vascularisation, the presence of microcalcifications and coexistence with other
      lesions in the goitre. Those features were correlated with the results of
      histopathological examinations. Altogether 356 lesions found in 284 patients were
      analyzed, of which 315 were non-neoplastic lesions, 12 - follicular neoplasms,
      and 29 - thyroid carcinomas. RESULTS: The small thyroid lesions were revealed in
      53.8% patients examined by US. The detailed analysis of US outcomes and the
      postoperative histopathological examinations showed that carcinomas with diameter
      <or= 10 mm when compared with small benign lesions presented more frequently as
      solitary lesions (48.2% vs. 16.2%; p < 0.001), hypoechoic (72.5% vs. 45.6%; p <
      0.01) and with microcalcifications (10.3% vs. 1.5%; p < 0.01). Moreover,
      carcinomas with extrathyroidal invasion were hypoechoic more frequently than the
      other carcinomas (90.0% vs. 36.8%; p < 0.05). CONCLUSIONS: The obtained results
      show the necessity for the limitation of number of performed biopsies in case of
      small thyroid lesions. They also provide rationale for consideration of some US
      features (like lowered echogenicity, the presence of microcalcifications or other
      lesions in the goitre) during selection of lesions to FNAB.

PMID- 17006828
TI  - [Chronic thyroiditis--current issue in the cytological diagnostics of the thyroid
      gland].
AB  - INTRODUCTION: Lowered and non-homogenous echogenicity in patients with chronic
      thyroiditis (CT) may cause problems in revealing focal lesions in ultrasound
      scans. Moreover, frequent anisocytosis of thyroid follicular cells and of
      oncocytes may falsely suggest neoplastic growth. The aim of the study was to
      evaluate the frequency of CT diagnosed in patients subjected to fine-needle
      aspiration biopsy (FNAB) of the thyroid in years 1994-2005, as well as to assess
      the cancer frequency in the operated patients with CT. MATERIAL AND METHODS: As
      much as 23 173 cytological reports and corresponding outcomes were analyzed and
      in patients treated surgically verified against postoperative histopathological
      examinations. Moreover, the analysis of cytological smears in CT with
      distinguishing its types (lymphocytic, epithelial-hyperplastic, colloidal,
      oxyphillic) was performed in 50 patients; the changes between subsequent FNABs in
      the picture of the smears were also assessed. RESULTS: The frequency of diagnosed
      CT had been increasing in the evaluated time span from 2.6% to 9.7% (p < 0.0001).
      There were 11 cases of papillary carcinoma found coexisting with CT. The analysis
      of cytological types of CT showed that the lymphocytic type prevailed over the
      others (lymphocytic - 43%, colloidal--21%, epithelial-hyperplastic--20%,
      oxyphilic--16%, p < 0.001). The evolution in time of the cytological picture was
      observed. CONCLUSION: The increase in the frequency of CT observed in smears
      obtained from the thyroid gland and the reports on the coexistence of CT with
      papillary carcinoma suggest the necessity of prudent diagnostics and follow-up of
      patients with CT.

PMID- 17006829
TI  - [Preliminary approach towards construction of peptide libraries as potential
      tools for diagnosis of malignant thyroid tumors].
AB  - INTRODUCTION: Cancer of thyroid gland is the most common malignancy of the
      endocrine system. The treatment improvement could be achieved by early diagnosis.
      The aim of the study was to identify cancer specific antigenes with use of
      peptide libraries. MATERIAL AND METHODS: The material from 6 patients with
      thyroid cancer (4 with papillary cancer, 1 with follicular cancer and 1 with
      oxyphilic tumor) were analyzed. It was performed with use of lipophylic peptide
      libraries by direct comparison of staining of specimens prepared from normal and
      malignant tissue. RESULTS: Preliminary results confirm practical value of peptide
      libraries in early diagnostics of thyroid cancer. CONCLUSIONS: It is important to
      optimize construction of peptide libraries by using different staining agents
      hydrolyzed by proteases.

PMID- 17006830
TI  - [Comparison of CD15, galectin-3 and HBME-1 expression in follicular thyroid
      neoplasms].
AB  - INTRODUCTION: Estimation of malignancy in thyroid follicular neoplasms is a
      common diagnostic problem, thus revealing of differences in expression of some
      antigens in both benign and malignant lesions seems to be essential. The aim of
      this study is to evaluate the immunohistochemical expression of CD15, galectin-3
      and HBME-1 in follicular adenomas and carcinomas. MATERIAL AND METHODS: Samples
      of 38 follicular adenomas (23 "classical", 5 with intracapsular invasion, 10
      oncocytic) and 15 follicular carcinomas (9 "classic", 6 oncocytic) were stained
      immunohistochemically with anti-CD15, galectin-3 and HBME-1. RESULTS: In the
      whole group we found statistically significant differences in CD15 expression
      between follicular adenomas and carcinomas. "Classic" follicular carcinomas
      (without oncocytic tumors) showed stronger CD15 and HBME- 1 expression than
      "classic" adenomas. Adenomas with intracapsular invasion differed from "classic"
      adenomas only in HBME-1 expression. In oncocytic tumors the expression of
      examined antigens was similar. CONCLUSIONS: 1. In the group of nonoxyphilic
      tumors positive reaction with HBME-1 was more common in adenomas with
      intracapsular invasion and carcinomas, but positive reaction with anti-CD15--only
      in carcinomas. We suggest that reactivity with these antibodies could mark
      malignancy. 2. Oncocytic tumors had similar expression of CD15 and HBME-1 and
      galectin-3.

PMID- 17006831
TI  - [Evaluation of p53 and soluble Fas ligand (sFasL) serum level concentration as
      indicators of apoptosis in serum of patients with benign and malignant primary
      follicular thyroid tumors].
AB  - INTRODUCTION: Apoptosis (programmed cell death) is the best described mode of
      physiological cell death. During embryonal development and morphogenesis,
      apoptosis may be induced by two pathways. The first is external protein signal
      originating from other cell--also named as "death signal". Another one is
      specific cell reaction for external stress factors. Blood concentration of
      proteins regulating both pathways of apoptosis may be useful in early diagnosis
      and staging of thyroid tumors. The aim of study was evaluation of p53 and sFasL
      blood concentration in patients with benign follicular adenoma and follicular
      thyroid cancer. MATERIALS AND METHODS: The study population was composed of 28
      patients: 14 with thyroid carcinoma and 14 patients with follicular neoplasm
      (NF). All patients underwent surgical treatment. P53 and sFasL levels were
      evaluated before surgery and related to the histopathological diagnosis obtained
      post-surgery. RESULTS: The analysis revealed high sFasL blood concentration in
      patients with follicular thyroid cancer in comparison with the group with
      follicular adenoma. There was no statistically significant difference between
      levels of p53 in both groups. CONCLUSIONS: Evaluation of sFasL serum level
      concentration may be useful in preoperative diagnosis of follicular thyroid
      tumors.

PMID- 17006832
TI  - [Expression of the selected adhesive molecules (cadherin E, CD44, LGAL3 and CA50)
      in papillary thyroid carcinoma].
AB  - INTRODUCTION: The aim of the study was to determine the expression of selected
      adhesive molecules in papillary thyroid carcinoma. MATERIAL AND METHODS: 47
      papillary thyroid carcinoma cases and 11 nonmalignant goiter cases were analyzed
      by immunohistochemistry. RESULTS: Galectin-3 (LGAL3) was a sensitive and specific
      marker, present in 91% of analyzed tumors and only in 5% of tumor margin. The
      presence of CA50 was 86% and 3% respectively with only 3% positive non-malignant
      cases. Cadherin E expression was noted in 91% of primary tumors, in 84% of the
      surrounding tissue and in 63% of non-malignant goiter. CD44 (DF1485) was observed
      in 89% of primary tumors and 48% of surrounding tissue; the reaction with BBA10
      was more characteristic for metastases. CONCLUSIONS: Our study confirms the high
      diagnostic value of galectin-3 in papillary thyroid carcinoma and reveals the
      similar efficiency of CA50. CD44 (DF1485) expression in primary tumor is more
      intensive than in surrounding tissue, but the diagnostical inportance is not high
      because it is often observed in benign lesions. Using of BBA10 is more sensitive,
      but less specific. High expression of cadherin E in benign lesions impairs its
      diagnostical application in papillary thyroid cancer.

PMID- 17006833
TI  - [Histopathological diagnosis of thyroid cancer in a multicenter trial].
AB  - INTRODUCTION: In the front of the problems related to the differentiation between
      benign and malignant thyroid tumors we decided to perform a multicentre study in
      order to validate diagnoses of malignant thyroid tumors and assess the inter
      observer variability. MATERIAL AND METHODS: Material included 690 cases of
      malignant and benign thyroid lesions with primary histopathology established in
      1985-1999. These cases were selected to multicentre study. The studies were sent
      from centres which agreed to participate in the project and than coded in the
      independent centre--Department of Nuclear Medicine and Endocrine Oncology. 40
      pathologists from 25 centres provided their diagnoses which were compared with
      the reference ones. RESULTS: 10 547 diagnoses were evaluated, both on their
      accuracy of the distinction between malignant and benign lesions and on their
      accuracy of cancer histotype definition. The reference diagnosis was made by an
      agreement between four expert pathologists (D.L., S.S., J.S. and A.K.). The
      participants diagnosed 21% of cases differently than experts. Concerning the
      diagnosis of cancer histotype, the difference between participants diagnosis and
      the reference one was even higher. The best concordance was achieved in the
      diagnosis of papillary thyroid cancer, however, on the cost of cancer
      overdiagnosis by some participants. Follicular cancer was diagnosed accurately
      only in 75.4% of cases. CONCLUSION: The study documents a high inter-observer
      variability of thyroid cancer diagnosis and confirms the lesser accuracy of
      diagnosis of follicular cancer.

PMID- 17006834
TI  - [Value of the intraoperative neuromonitoring in surgery for thyroid cancer in
      identification and prognosis of function of the recurrent laryngeal nerves].
AB  - INTRODUCTION: The aim of this study was both, to evaluate the usefulness of the
      method of neuromonitoring in intraoperative identification of the RLN and to
      estimate its value in the prognosis of postoperative RLN function in patients
      operated for TC. MATERIAL AND METHODS: Among 109 patients undergoing surgery for
      TC between 12/2004 and 12/2005 the neuromonitoring method was used in 69 (63.3%)
      individuals (including 5 operations of completion total thyroidectomy). A
      Neurosign 100 equipment with laryngeal electrodes was employed in identification
      and assessment of total number of 134 RLN. Intraoperative results were compared
      to the postoperative results of the ENT-specialist examination of vocal cords
      mobility in indirect laryngoscopy, in each patient. RESULTS: Transient vs.
      permanent, unilateral RLN palsy was noted in 3 vs. 2 patients (2.2% vs. 1.4% of
      nerves at risk). The method of neuromonitoring facilitated identification of 123
      (91.8%) RLN being not helpful in 11 (8.2%) cases. However, neuromonitoring was
      helpful in identification of the RLN, the value of the method in prognosis of
      posteoperative function of the RLN was limited. Results of indirect
      neurostimulation were more accurate than direct neurostimulation and were more
      accurate in prognosis of late rather than early RLN function after surgery
      (sensitivity 98.3%; specificity 100%; positive predictive value 100%; negative
      predictive value 50%, accuracy 98.4%). CONCLUSIONS: Application of intraoperative
      neuromonitoring facilitates identification of the RLN during surgery for TC.
      However, the method is of limited value in prognosis of postoperative RLN
      dysfunction in cases of missing signal after nerve stimulation.

PMID- 17006835
TI  - [The impact of the extent and time of operation on the survival in patients with
      differentiated thyroid carcinoma (DTC)].
AB  - INTRODUCTION: To analyze the impact of time and extent of operation on overall
      and disease-free survival in patients with differentiated thyroid carcinoma
      (DTC). MATERIAL AND METHODS: Retrospective analysis of 1235 DTC patients, a
      representative probe of patients diagnosed or treated between 1986 to 1998 was
      performed. 277 patients were staged T1M0 and 958 ones staged > T1M0. 10-year
      outcomes were analyzed by Kaplan-Meier survival curves and Cox proportional
      hazard model. RESULTS: The T1M0 patients were characterized by the best overall
      and disease-free survival independently of the time and the extent of operation
      (98% and 96% respectively); in > T1M0 group the survival was better in patients
      who were treated by total thyroidectomy (94% and 68% respectively) than in
      patients treated by non-total thyroidectomy (78% and 47% respectively). In
      patients treated by completion of total thyroidectomy delayed more than 1 year
      post cancer diagnosis the incidence of carcinoma in postoperative pathological
      material was twice as high in comparison to the group in whom total thyroidectomy
      was performed within the first year of therapy (p = 0.000). CONCLUSIONS: 1. In
      differentiated thyroid carcinoma the prognosis is related to the extent of
      operation only in patients staged more than T1M0. 2. A delay > 12 months in
      completion surgery in patients with differentiated thyroid cancer (tumors > 1 cm
      of diameter) significantly increases the risk of progression of multifocal
      disease in thyroid remnants.

PMID- 17006836
TI  - [Completion total thyroidectomy in children with differentiated thyroid cancer].
AB  - INTRODUCTION: The optimal surgical treatment of children with differentiated
      thyroid cancer remains an important point of discussion. Especially the need for
      completion operation is questioned in young patients. Our objective was to
      examine the rate of residual neoplastic disease after non radical initial
      operation. MATERIAL AND METHODS: From the 235 children diagnosed with
      differentiated thyroid cancer, 131 (56%) needed completion operation due to
      incomplete primary surgery. Completion operation involved thyroid bed, lymph
      nodes or both respectively in 91 (39%), 13 (6%) and 27 (11%) cases. Risk factors
      responsible for residual disease were evaluated by means of logistic regression
      analysis. RESULTS: Residual disease was detected in 46 (35%) of reoperated
      children (25% in thyroid bed and 85% in lymph node of lateral neck compartment).
      Sex and age did not influence the risk of residual disease in thyroid bed or
      lymph nodes. Papillary type of cancer and multifocality increased risk of
      residual disease in thyroid bed respectively by the factor of 15 (95% CI: 2-125)
      and 2.3 (95% CI: 1.2-4.4). Infiltration of thyroid capsule did not correlate with
      the risk of residual disease. Lymph node metastases in primary operation
      increased risk of residual disease by the factor of 16 (95% CI: 1.2-245).
      Histopathology, multifocality of primary tumour or infiltration of lymph node
      capsule did not influence the risk of residual disease in lymph nodes of lateral
      neck compartment. CONCLUSIONS: In children with differentiated thyroid cancer
      residual disease is diagnosed in about 1/3 of non radically operated cases. This
      high incidence justifies completion operations. The risk of residual disease is
      significantly increased in papillary thyroid cancer, multifocal tumours and cases
      with lymph node metastases.

PMID- 17006837
TI  - [Evaluation of the therapeutic benefits in relation to the extent of surgery in
      patients with differentiated thyroid carcinoma].
AB  - INTRODUCTION: Evaluation of the therapeutic benefits in relation to the stage of
      thyroid cancer and to the extent of surgery and the risk of postoperative
      complications. MATERIAL AND METHODS: Retrospective analysis of differentiated
      thyroid carcinoma (DTC) patients staged T1M0 versus T2-T4M0 was performed. All of
      them were treated or diagnosed in Institute of Oncology in Gliwice between 1986
      1998. Previously they were operated in various surgical centers all-over Poland.
      The risk of death, local relapse and postoperative complications were analyzed
      using the decisiontree model to evaluate the therapeutic benefits. RESULTS: The
      recurrent laryngeal nerve injury (transient or permanent) was observed in
      retrospective analysis in 21% of patients, while postoperative
      hyperparathyroidism in 15.8%. The analysis of the therapeutic benefit index
      showed no advantage of total thyroidectomy in the T1M0 group (0.96 vs. 0.98 in
      patients treated by less than total thyroidectomy). The advantage of radical
      surgery was confirmed in T2-T4M0 group. The therapeutic benefit index was 0.92 in
      patients treated by total thyroidectomy and 0.69 in those who received less
      extensive operation. CONCLUSIONS: The analysis of therapeutic benefits confirmed
      the limit of 1 cm tumor diameter between less extensive surgery and total
      thyroidectomy. It showed that total thyroidectomy brings a significant
      therapeutic benefits in patients in > T1M0 stage. The improvement of overall
      survival and decrease of local relapse far outweigh the disadvantages related to
      postoperative complications.

PMID- 17006838
TI  - An evaluation of the value of first thyroglobulin determination in the
      diagnostics of metastases immediately following differentiated thyroid carcinoma
      surgery.
AB  - INTRODUCTION: Evaluation of the differential value of the first thyroglobulin
      (Tg) concentration, measured after thyroidectomy (Tx) but before thyroid remnant
      ablation, in patients with differentiated thyroid carcinoma (DTC) as a marker of
      either metastases or residual cancer (M). MATERIAL AND METHODS: Data from 517
      patients with DTC after Tx, with follow-up > 1.5 year were analysed
      retrospectively. Patients in whom either the course of the disease was unclear or
      interference in the Tg test was possible (a-TgAb [+], Tg recovery < 80%) were
      excluded from the study. Finally, the data from 247 patients were evaluated (age:
      14-79 years; 223 women, 24 men). The results of TSH, thyroid radioiodine uptake
      (T(up24)), thyroid remnant volume (V) and Tg in patients with diagnosed M (group
      M1; n = 35) were compared with the same parameters in patients with remission >
      1.5 year (group M0; n = 212). The area under the ROC curve was calculated. The
      clinical decision limit of Tg level to be suggestive of metastases was determined
      by means of efficiency curve. RESULTS: Groups M0 and M1 did not differ from each
      other with respect to TSH concentration (median 49.7 mIU/l vs 44.3; p = 0.16) or
      thyroid remnant volume (1.4 vs 1.1 ml; p = 0.79). However, they did differ with
      respect to T(up24) (7.6 vs 3.2%; p = 0.01) and Tg (4.5 vs 96.7 ng/ml; p =
      0.000000). Area under ROC for Tg was 0.78 +/- 0.05 (mean +/- s.e.m.). The
      decision limit of Tg for suspected M was determined at 38.1 ng/ml, Tg sensitivity
      was 0.57 (95%CI 0.39-0.74) and specificity 0.96 (95%CI 0.92-0.98). CONCLUSIONS:
      First thyroglobulin concentration, determined after thyroidectomy but before
      other treatment, is higher in patients with metastatic DTC than in patients
      without such metastases. This indicates that Tg level may be used as an early
      marker of either residual or metastatic DTC (even if thyroid remnants are
      present).

PMID- 17006839
TI  - [Optimization of 131I ablation in patients with differentiated thyroid carcinoma:
      comparison of early outcomes of treatment with 100 mCi versus 60 mCi].
AB  - INTRODUCTION: The aim of this study was to compare the early outcomes between two
      groups of patients with differentiated thyroid carcinoma (DTC) who received 60 or
      100 mCi of (131)I for remnant ablation. MATERIAL AND METHODS: 224 DTC patients
      with primary tumor > 1 cm of diameter or multifocal were randomised into
      prospective clinical trial. Patients with extrathyroideal extension of primary
      tumor and nodal metastases or M1 were not enrolled. 99 patients received 60 mCi,
      and 125--100 mCi of radioiodine as the first ablative dose. RESULTS: The
      effectiveness of thyroid ablation was evaluated after one year, during endogenous
      TSH (thyroid stimulating hormone) stimulation, and after two years during
      Lthyroxine therapy. Whole body scintigraphy (WBS) was performed under thyroxine
      withdrawal and thyroglobulin serum level was assessed. Distant micrometastases
      were detected in 9.8% of patients by post-therapy WBS, 11 patients in group A
      treated with 60 mCi and 11 in group B treated with 100 mCi. In other patients no
      symptoms of persistent disease were detected. At one year follow up full
      remission was diagnosed in 176 patients: 76 in group A and 100 in group B. The
      remaining ones, 13.3% and 11.2% respectively, received the second course of
      (131)I for remnant ablation. There were no statistically significant differences
      in Tg (thyroglobulin) serum level either 12 or 24 months after 131I treatment.
      CONCLUSIONS: Our evaluation of early efficacy of adjuvant radioiodine treatment
      in low risk DTC patients shows no differences between two radioiodine activities 
      60 and 100 mCi in relation to thyroid ablation. Thus, the activity of 60 mCi is
      recommended.

PMID- 17006840
TI  - [Diagnostic scintigraphy and effectiveness of 131I radioiodine therapy in
      differentiated thyroid carcinoma (DTC)].
AB  - INTRODUCTION: Since the effect of pre-therapeutic scintigraphy on the outcome of
      DTC treatment is debated, we evaluated factors affecting the effectiveness of
      (131)I therapy with respect to the delay between diagnostic scintigraphy and the
      application of radioiodine. MATERIAL AND METHODS: In the studied group of 60
      patients with DTC, mean age 54.6 +/- 13.0 years, four weeks prior to the planned
      diagnostics, L-thyroxine was withdrawn and the following tests performed: (131)I
      (4 MBq) uptake above the neck, thyroid volume by USG, TSH and hTg level.
      Wholebody scintigraphy (37 MBq) was performed. The time between this diagnostic
      scintigraphy and application of (131)I (3657 MBq) was calculated. Based on whole
      body 131I scintigraphy (74 MBq) performed 1 year after radioiodine treatment, the
      patients were divided into: group I - 42 patients with no tracer accumulation,
      and group II--18 patients who continued to accumulate (131)I in the neck.
      RESULTS: The differences between the median values of (131)I uptake and of
      thyroid volumes, and between the TSH and hTg median values in the two groups of
      patients were found not to be statistically significant. The average times
      between diagnostic scintigraphy and (131)I treatment in group I and II (9.4 vs.
      8.3 weeks, respectively) were not significantly different either. CONCLUSION:
      Despite the different effectiveness of supplementary (131)I treatment, patients
      in group I and group II showed no statistically significant differences in the
      studied parameters. It appears that the diagnostic (131)I activity of 37 MBq and
      the time between diagnostic scintigraphy and application of (131)I did not have
      any effect on the results of the treatment in our group of patients.

PMID- 17006841
TI  - [Relapse of differentiated thyroid carcinoma in low-risk patients].
AB  - INTRODUCTION: The low incidence of relapse in differentiated thyroid carcinoma
      (DTC), primarily treated by total thyroidectomy and (131)I ablation, stimulates
      the search for optimal follow-up algorithms which do not include too many tests
      but are not connected with a risk of missing early recurrence. The aim of the
      study was to analyze the impact of the routine follow up examinations for early
      detection of DTC recurrence in low risk DTC patients. MATERIAL AND METHODS: The
      group consisted of 617 DTC patients diagnosed in 1995-1996. In 513 (83%) total
      thyroidectomy was performed. 449 (73%) received ablative (131)I therapy. After
      primary approach complete remission (CR) was stated in 453 (73%), persistent
      disease in 116 (19%), asymptomatic hyperthyroglobulinaemia in 14 (2%). Patients
      with CR constituted the low risk group analyzed in this study. The median follow
      up was 4.16 yrs. RESULTS: Recurrent disease appeared in 28 (6%) patients (23
      locoregional, 9 distant metastases, both in 4). Serum Tg (thyroglobulin) level at
      the moment of relapse diagnosis was detectable in 44% while neck sonography was
      the first examination to detect recurrence in 56% of cases. CONCLUSION: In the
      selected group of DTC patients treated by radical primary approach and showing a
      low risk of recurrence only half of all relapse cases are diagnosed by the rise
      of serum Tg level. Regular sonography contributes to the second half of
      diagnoses. Thus, a special weight should be put on neck sonography as the
      important element of regular follow up in low risk DTC patients.

PMID- 17006843
TI  - [Indications for surgery of thyroid cancer based on bioptate molecular
      examination].
AB  - INTRODUCTION: In differentiated thyroid cancer (DTC) the differentiation between
      reactive and metastatic lymph nodes is difficult at the early stages of
      metastasis. The aim of the study was to assess the results of fine needle
      aspiration (FNA) samples examination by the use of RT-PCR for Tg mRNA. The
      special attention was directed to the evaluation of specificity of TgRNA
      estimation. MATERIAL AND METHODS: The group consisted of 193 DTC patients with
      suspicion of lymph node recurrence and at least one positive RT-PCR result.
      Thyroglobulin RT-PCR was conducted in residual material left after preparation of
      cytological smears from FNA specimens. Primer spanning exons 3-5 were used with
      39 cycles of PCR. RNA isolation control and cDNA amplification were carried out
      using GAPDH starters. 308 lymph node biopsies were included. RESULTS: 246
      positive results for Tg RNA were observed in the analyzed group, 71.1% confirmed
      by FNA. Among other 71 results, in which cytological examination did not
      correspond unequivocally to molecular findings, in 34 metastases were confirmed
      both by cytological and clinical examination. There were 11 patients operated due
      to the positive serial molecular examination only. In 10 (91%) of them DTC
      metastases were confirmed. So, the positive predictive value of the molecular
      result ranged between 75-89% and the negative one was 100%. CONCLUSIONS: In DTC
      patients RT-PCR Tg mRNA is helpful in qualification of suspicious lymph nodes to
      surgery in DTC patients. At the negative cytological finding, the positive
      molecular result constitutes an indication for early surgery.

PMID- 17006842
TI  - The diagnostic value of thyroglobulin concentration in fine-needle aspiration of
      the cervical lymph nodes in patients with differentiated thyroid cancer.
AB  - INTRODUCTION: Recurrent differentiated thyroid cancer generally occurs first in
      the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but
      is not specific enough. Ultrasound-guided fine-needle biopsy increases the
      specificity but still may fail to detect a recurrence of the disease in the
      cystic metastatic lymph nodes. The aim of the study was to estimate the value of
      Tg concentration in the needle washout after fine-needle aspiration of suspicious
      lymph nodes. MATERIAL AND METHODS: The 105 patients studied had presented one or
      more enlarged suspicious cervical lymph nodes. All had undergone total
      thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration
      was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94
      100%. The positive Tg washout concentration cut-off value was established as
      equal to the mean plus two standard deviations of the Tg washout concentration of
      patients with negative cytology. RESULTS: Lymph node involvement was diagnosed by
      cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration
      was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned
      out to have positive cytology had a positive Tg washout concentration. All lymph
      nodes with positive cytology were positive in pathology. Seven patients and 20
      lymph nodes with negative cytology were positive in the Tg washout concentration
      test. All but one patients and all but two lymph nodes with a positive Tg washout
      concentration had positive pathology. CONCLUSIONS: 1. Ultrasound-guided fine
      needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2.
      The Tg washout concentration test is 100% sensitive in the detection of
      metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is
      100% specific. 4. The Tg washout concentration test carries a risk of false
      positive results. 5. Both methods should be used for early detection of
      metastatic lymph nodes in patients with differentiated thyroid cancer.

PMID- 17006844
TI  - [Application of 13-cis-retinoic acid in patients with 131I scintigraphically
      negative metastases of differentiated thyroid carcinoma].
AB  - INTRODUCTION: The loss of iodine uptake by differentiated thyroid carcinoma (DTC)
      cells is a major therapeutic problem especially in patients with nonsurgical
      metastatic foci or local recurrence. Using 13-cis-retinoic acid, it was attempted
      to retain iodine uptake as a result of redifferentiation (influence by retinoic
      acid receptors present in DTC cells). MATERIAL AND METHODS: Between 1999 and
      2005, 13-cis-retinoic acid was used in 11 patients with disseminated PTC and high
      serum level of thyroglobulin (Tg) before (131)I treatment (2 patients were
      treated twice - 13 treatment cycles in total). Side effects in skin and mucous
      membranes were observed in all the patients, however, their intensity did not
      require termination of the therapy. RESULTS: Increase of iodine uptake was
      observed in 5 patients (45%). Decreased Tg concentration was observed in 9
      patients. In that group, increased (131)I uptake was observed in 4 patients with
      distant metastases. All determinations of Tg concentrations were carried out
      under TSH stimulation. CONCLUSIONS: 13-cis-retinoic acid causes an increase of
      radioiodine uptake in around half of treated patients, however, the follow-up of
      these patients indicates that this increase does not result in either full
      remission or even stabilisation of neoplastic disease. The possibility should be
      considered to use cis-retinoic acid as an independent therapeutic approach in
      patients with radioiodine non-avid foci of thyroid carcinoma especially those
      showing high expression of RARb and RXRg receptors.

PMID- 17006845
TI  - [Medullary thyroid carcinoma: the comparison of the hereditary and sporadic types
      of cancer].
AB  - INTRODUCTION: The assessment of frequency and type of mutation and differences in
      prognosis between sporadic and hereditary type of medullary thyroid carcinoma
      (MTC), based on own DNA analysis, was performed. MATERIAL AND METHODS: The group
      of 190 persons with hereditary MTC or asymptomatic mutation carriers was
      analyzed. Patients with sporadic MTC without RET gene mutation were included into
      control group (708 persons). The recognition of MTC type was based on assessment
      of family history, physical examination and genetic analysis. The family history
      consisted of information about MTC, pheochromocytoma and other neoplasms and
      hyperparathyroidism in relatives. RESULTS: The mutations located in codon 634 of
      exon 11 were the most often (43% of all mutations and 49% of mutations in
      syndrome MEN 2A/FMTC). The age of diagnosis was ranged between 7 and 71 years
      (mean age: 39 +/- 15.2 years, median age: 41 years). In hereditary MTC the mean
      age of diagnosis was 27 +/- 13.9 years and was significantly lower than in
      sporadic one, where it was 45.7 +/- 14.3 years. The relationship between
      diagnosis, age and subtypes of hereditary MTC was assessed--no significant
      differences in examined subgroups were observed. The mean age of diagnosis in MEN
      2A/FMTC and MEN 2A syndrome was 28-29 years, in MEN 2B - 21 years. The overall
      survival in sporadic MTC after 5 years was 97%, in hereditary MTC - 79%. Analysis
      performed after excluding suprarenal causes of death revealed no statistically
      significant differences in overall survival between both subtypes of MTC.
      CONCLUSIONS: 1. Hereditary MTC is still diagnosed too late, besides of DNA
      analysis. 2. In hereditary and sporadic MTC the prognosis is comparable.

PMID- 17006846
TI  - [Clinical and genetic profile of patients with medullary thyroid cancer treated
      in the Cancer Centre--Institute of Oncology in Warsaw].
AB  - INTRODUCTION: The aim of this study was to analyse the distribution and frequency
      of mutations and their correlations with clinical phenotypes of patients with
      MTC, to reveal the differences between sporadic and familial type of MTC, and to
      describe the phenotypes of patients. MATERIALS AND METHODS: 212 patients with
      medullary thyroid cancer (MTC) were treated in Cancer Centre in Warsaw between
      1997 and 2005. In most patients, DNA isolated from peripheral blood leukocytes
      was tested for RET gene mutations by sequencing and accordingly MTC form was
      assessed. Genetic testing was performed in the relatives of patients with
      familial MTC in order to distinguish asymptomatic mutation carriers from
      noncarriers. RESULTS: RET gene mutations were identified in 46 patients (22%).
      The others were found noncarriers and sporadic MTC was diagnosed. MEN 2A/FMTC
      syndrome (multiple endocrine neoplasia type 2A/ familial type of MTC) was
      diagnosed in 44 patients, MEN 2B syndrome (multiple endocrine neoplasia type 2B)
      in 2 patients. In patients with sporadic and familial MTC, age at diagnosis and
      multifocal occurrence was analysed, and the results were found to be in
      accordance with those of other research centres. However, the distribution and
      frequency of mutations, as well as some clinical data, such as the frequency of
      pheochromocytoma occurrence as the first manifestation of MEN syndrome, differed
      from the published data, and further studies are necessary to reveal the reasons
      of these differences. CONCLUSIONS: DNA testing for RET gene mutations is reliable
      as a diagnostic tool and therefore it should be performed for screening of all
      patients with MTC or other diseases of MEN syndrome.

PMID- 17006847
TI  - [Gene expression profile of medullary thyroid carcinoma--preliminary results].
AB  - INTRODUCTION: Medullary thyroid carcinoma occurs both as a sporadic and a
      familial disease. Inherited MTC (iMTC) patients usually exhibit better prognosis
      than patients with sporadic form of MTC (sMTC), however, in both subtypes the
      outcome is unpredictable. No molecular markers contributing to the prognosis or
      predicting the type of therapy have been introduced to clinical practice until
      now. The aim of this study was to analyze gene expression pattern of MTC by high
      density oligonucleotide microarray. MATERIAL AND METHODS: 24 samples were
      studied: 12 MTC and 12 corresponding normal tissues, (Affymetrix HG-U 133A).
      Among MTC patients there were half inherited cases and half sporadic ones.
      RESULTS: First, the differences between MTC and thyroid tissue were analyzed by
      Singular Value Decomposition (SVD) which indicated three main modes determining
      the variability of gene expression profile: the first two were related to the
      tumor/normal tissue difference and the third one was related to the immune
      response. The characteristic expression pattern, beside of numerous changes
      within cancer- related genes, included many up-regulated genes specific for
      thyroid C cells. Further analysis of the second component revealed two subgroups
      of MTC, but the subdivision was not related to the iMTC/sMTC difference.
      Recursive Feature Replacement (RFR) confirmed the very similar expression profile
      in both forms of MTC. With subsequent ANOVA analysis some genes with differential
      expression could be specified, among them monoamine oxidase B (MAOB) and gamma
      aminobutyric acid receptor (GABRR1) which were consistently up-regulated in sMTC.
      In contrary, some genes involved in regulation of cell proliferation: opioid
      growth factor receptor(OGFR) and synaptotagmin V (SYT 5) were up-regulated in
      iMTC. CONCLUSIONS: The obtained data indicate a very similar gene expression
      pattern in inherited and sporadic MTC. Minor differences in their molecular
      profile require further analysis.

PMID- 17006848
TI  - [The use of a new analogue DGlu-Octagastrin in scintigraphy of medullary thyroid
      carcinoma].
AB  - INTRODUCTION: Medullary thyroid carcinomas (MTC) reveal overexpression of several
      peptide receptors particularly of gastrin and cholecystokinin 2 (CCK2).
      Experimental studies of various CCK-2/gastrin analogues found that a C-terminal,
      8-aminoacid peptide, (D)Glu-octagastrin, has optimal properties. Thus, the aim of
      our studies was to prepare (99m)Tc-labelled HYNIC-octagastrin, to evaluate its
      biologic tolerance in animals and introduce for scintigraphy in patients with
      MTC. MATERIAL AND METHODS: HYNIC-(D)Glu-octagastrin was from piCHEM (Graz,
      Austria), (99m)Tc generator from Amersham (Health), other reagents were purchased
      from Sigma. Labelling of the peptide was performed in phosphate buffer of pH 6.0
      for 10 minutes at 100(o)C using EDDA and tricine as coligands. RESULTS: The
      labeling yields were high (above 95%); the specific activity amounted to 1200 to
      1430 microCi/microg. Radiochemical purity on SepPak cartridge and ITLC ranged
      from 94 to 98%. No adverse effects were observed in mice after administration of
      10 to 50 times greater doses that those used in patients. Clinical studies
      comprised 20 patients with MTC and high serum calcitonin. (99m)Tc-EDDA/HYNIC
      (D)Glu-octagastrin, 500 to 700 MBq, was administered iv and whole body
      scintigraphy was performed using a double head gamma-camera (Varicam, Elscint) 2
      and 4 hours later. Increased accumulation of the tracer in foci of MTC and its
      metastases was found in 8 patients. CONCLUSIONS: Scintigraphy with a new gastrin
      analogue ((D)Glu-octagastrin) makes it possible to detect MTC with overexpression
      of CCK-2/gastrin receptors and to select patients for receptor-mediated
      radiopeptide therapy using DOTA-gastrin analogues labelled with (177)Lu and
      (90)Y.

PMID- 17006849
TI  - [The role of scintigraphy with the use of 99mTc-HYNIC-TOC in the diagnosis of
      medullary thyroid carcinoma].
AB  - INTRODUCTION: Recently a new somatostatin analogue labelled with (99m)Tc ((99m)Tc
      HYNIC-TOC) has been synthetized. Aim of this study was to evaluate the utility of
      (99m)Tc-HYNIC-TOC in the radionuclide imaging in patients with medullary thyroid
      carcinoma (MTC). MATERIAL AND METHODS: 30 patients with MTC aged 22-83 years in
      different stages of the disease were investigated. In 6 patients (group 1)
      scintigraphy was performed before surgery directly after diagnosis of MTC. Four
      patients (group 2) were qualified to the study in the phase of remission after
      surgical treatment that had been confirmed by low concentrations of calcitonin.
      Twenty patients (group 3) were investigated due to stagnation or recurrence
      confirmed by persistent hypercalcitoninemia. The scintigraphy using (99m)Tc-HYNIC
      TOC (Tektrotyd, POLATOM) was performed 2 and 4 hours post injection of 20 mCi
      (740 MBq) of the tracer. Other imaging techniques were also employed and analysed
      in individual cases (US, CT, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In
      octreotide and FDG-PET). RESULTS: Images obtained 2 and 4 hours p.i. were
      similar. In group 1, uptake of the tracer was found in the primary tumour of MTC
      in all patients. In group 2, a false positive result was found in 1 of 6
      patients. In the remaining 5 of 6 cases no pathological foci were visualised. In
      group 3, uptake in the thyroid bed was found in 3 of 20 cases and in the lymph
      nodes in 14 of 20 patients. In 3 of 20 cases uptake in the bone metastases was
      found. Globally, sensitivity of the scintigraphy using (99m)Tc-HYNIC-TOC was
      86.4%, specificity - 75.0%, and accuracy - 84.6%. CONCLUSION: The scintigraphy
      using (99m)Tc-HYNIC-TOC showed high utility in the diagnosis of MTC. Confirmation
      of the presence of somatostatin receptors with this method may be used for
      treatment planning: surgery or radionuclide therapy.

PMID- 17006850
TI  - [BRAF initiating mutations in the papillary thyroid carcinoma].
AB  - Among genetic alterations most important for the initiation of papillary thyroid
      carcinoma (PTC) is mutation T1799A in the BRAF gene which is the most frequent
      event (54.5%) in this type of thyroid cancer. It is seen in all stages, from
      microcarcinoma through clinically overt disease to anaplastic cancer. It has been
      shown that BRAF mutation is correlated with PTC histotype. It is identified most
      frequently in classical PTC and in tall cell variant. Moreover, BRAF mutation is
      described more often in older patients, whereas in young patients RET/PTC
      rearrangements dominate. In PTC cases with BRAF mutation V600E the prognosis is
      poorer, with more cancer invasiveness, metastasis and recurrence. The presence of
      BRAF mutation is related to the specific gene expression signature, different
      than in cancer cases showing RET/PTC rearrangement or no known initiating
      mutation.

PMID- 17006852
TI  - Positron emission tomography (18FDG-PET) in the detection of medullary thyroid
      carcinoma metastases.
AB  - INTRODUCTION: Medullary thyroid carcinoma (MTC) is usually more advanced at
      presentation than differentiated thyroid cancers and often has distant
      metastases. The primary treatment of MTC is total thyroidectomy and regional
      lymph node dissection. The efficacy of these procedures has been limited by the
      aggressiveness of the disease and metastatic spread at the time of surgery.
      Persistently elevated levels of calcitonin (CT) and carcinoembryonic antigen
      (CEA) or their increase postoperatively are indicative for residual or recurrent
      disease. Conventional imaging methods such as ultrasonography, computed
      tomography, magnetic resonance imaging and MIBI scintigraphy usually fail to find
      the source of calcitonin. Better imaging properties have been shown by DMSA
      scintigraphy, somatostatin receptor scintigraphy or by positron emission
      tomography (PET). The aim of the study was to evaluate the diagnostic accuracy of
      PET for the localisation of occult MTC in patients after surgery with increased
      concentrations of CT, in whom conventional imaging procedures have not been
      successful. MATERIAL AND METHODS: The PET investigation using (18)F-fluoro- 2
      deoxy-D-glucose combined with computed tomography ((18)FDG-PET/CT) was performed
      at the Department of Nuclear Medicine (Oncology Centre in Bydgoszcz) between
      January and October 2004. In five patients with postoperative calcitonin ranging
      from 164 to > 2000 ng/l (normal < 10 ng/l) no tumour lesions were found using
      other imaging methods. RESULTS: In four of five cases, responsible lesions with a
      higher metabolism of FDG, indicating MTC tissue (remnants or metastases), were
      localised. In one patient no focus of FDG accumulation was found despite high CT
      concentration. PET detected tumour manifestations in the neck and the mediastinum
      in two patients, in the lung and the left adrenal gland in one case and in the
      neck and the liver in another patient. As a result of surgery for the removal of
      a residual tumour or metastases the accuracy of diagnosis was confirmed by
      histopathology in all four cases and a decrease in CT and CEA levels was observed
      in 3/4 cases. The metabolic imaging findings by PET/CT ensured that the surgery
      on these patients was successful. CONCLUSIONS: For the detection of occult
      residual or metastatic MTC lesions, (18)FDG-PET is a valuable procedure in
      imaging diagnostics.

PMID- 17006851
TI  - [Recombinant human TSH stimulation in radioiodine treatment of disseminated
      differentiated thyroid cancer--update of current and our own experiences].
AB  - Traditionally, for diagnostic and therapeutic application of radioiodine in
      patients with differentiated thyroid cancer (DTC), a 4 to 6 week withdrawal of
      thyroid hormone was applied. Recombinant human TSH (rhTSH) was developed to
      provide TSH stimulation without withdrawal of thyroid hormone and associated
      morbidity. The results of rhTSH administration and endogenous TSH stimulation are
      equivalent in detecting recurrent DTC. At the present time rhTSH is approved as
      an adjunct for diagnostic procedures and thyroid ablation in patients with DTC.
      In addition, rhTSH has potential for use in facilitating the treatment of
      metastases in patients with DTC. In this review we have summarized our own
      experiences with rhTSH aided radioiodine therapy in patients with disseminated
      thyroid cancer. Generally, rhTSH was very well tolerated and treatment results
      were comparable to those achieved with thyroid hormone withdrawal.

PMID- 17006855
TI  - [Reflections on the role of primary health care in outpatient neurological
      services].

PMID- 17006856
TI  - [Prior authorisation to visit the neurologist from primary care may not be
      necessary: the findings of a prospective, controlled study].
AB  - INTRODUCTION: The system by which approval must be given by the primary care
      physician before a patient can visit a specialist is known as gatekeeping and is
      aimed at preventing the mistaken or simple referral of patients to the next stage
      of health care services. We present a study that compares the final diagnoses of
      400 patients who used a direct access model of referral (DAM) with those of 400
      patients referred by a primary care physician in a prior authorisation model
      (PAM). PATIENTS AND METHODS: We conducted a prospective analysis of two cohorts
      of patients who visited the same neurologist in a PAM system versus a DAM system.
      The 800 patients were evaluated following similar diagnostic criteria. The
      primary objective of the study was to compare the patients who were referred with
      a final diagnosis of 'non-neurological pathology' in the PAM and the DAM systems.
      Secondary aims consisted in conducting an analysis of the diagnoses by different
      pathologies between the two models. RESULTS: No significant differences were
      found between the referrals that were considered to be non-neurological in the
      PAM and the DAM systems (27.0% versus 26.3%; p = 0.48). A logistic regression
      model was performed with 'non-neurological pathology' as the dependent variable
      and age, sex and type of model (PAM or DAM) as the independent variables, similar
      results being obtained in both cases. CONCLUSIONS: Our data suggest that the role
      played by the primary care physician is not effective when it comes to preventing
      mistaken referrals to the neurologist in our area. A populational study would be
      needed to evaluate the rate at which resources are used and the spending on
      health care in the two models.

PMID- 17006857
TI  - [Effectiveness and safety of levetiracetam in 133 children with medication
      resistant epileptic seizures].
AB  - INTRODUCTION: Levetiracetam (LEV) is the latest drug approved in the European
      Union for use in polytherapy in children over 4 years of age with partial
      epileptic seizures that are resistant to other antiepileptic drugs. AIM. To
      report our experience of associating LEV in children with medication resistant
      epileptic seizures. PATIENTS AND METHODS: We conducted an open, observational,
      respective study involving 133 children with refractory epilepsies: 106 with
      focal seizures and 27 with other types of seizures. LEV was associated over a
      period of more than 6 months and we evaluated its repercussion on the frequency
      of the seizures and the side effects related to the drug. RESULTS: With average
      doses of LEV of 1,192 +/- 749 mg/day the frequency of the seizures was reduced by
      over 50% in 58.6% of cases and seizures were quelled in 15.8% of patients. Side
      effects were produced in 27.8% of cases, and were usually transient or tolerable;
      these effects led to withdrawal of LEV in only eight cases (6.02%). In 37
      children (27.8%), their relatives noted an improvement in their social behaviour
      and cognitive abilities. CONCLUSIONS: a) LEV is an effective drug that is well
      tolerated in children with refractory epilepsy; b) Its effectiveness in different
      types of seizures indicates a broad therapeutic spectrum; and c) LEV can even
      condition favourable secondary effects, a circumstance that has been reported
      only exceptionally in the case of other antiepileptic drugs.

PMID- 17006859
TI  - [Lesion of extrahippocampal cortices of left medial temporal lobe: a case
      report].
AB  - INTRODUCTION: The cortex of medial temporal lobe is a group of different
      allocortical fields which included the hippocampal formation (dentate gyrus,
      hippocampus proper, and subicular complex) and extrahippocampal cortices
      (entorhinal, perirhinal, and parahippocampal). It is widely accepted that both of
      them play an important role in memory process. In humans, several reports
      indicates that damage to the hippocampus alone would lead to a clinically
      significant amnesia; when the injuries are more extensive others cognitive
      disorders, as those related to visual sphere, make worse the clinic picture, and
      some of these cases were reported as associative visual agnosias. Nevertheless,
      although evidence from animal studies points to the importance of the
      extrahippocampal medial temporal lobe cortices in order to recognise visual
      stimuli, such involvement has not been demonstrated in humans. CASE REPORT: A 44
      year-old male who consulted us because they had lost about of '80% of his vision'
      after a stroke. Ophthalmological examination was entirely within normal limits,
      but neuropsychological test put in evidence difficulties in the visuo-verbal
      naming, discrimination of superposed images, recognition of faces and, mainly, in
      the test of immediate and deferred visual memory. Anterograde memory impairment
      was also revealed. Magnetic resonance imaging showed a lesion of left entorhinal,
      perirhinal and parahippocampal cortices. CONCLUSIONS: We suggest, in relation to
      anatomical evidences, that isolation of hippocampus is responsible for
      symptomatollogy of our patient.

PMID- 17006858
TI  - [The effects of bromazepam on contingent negative variation and reaction time in
      a visuomotor task].
AB  - INTRODUCTION: Bromazepam is the second most commonly used benzodiazepine in
      Brazil. Psychophysiological research on this substance is still in its early
      stages. AIM: To determine the neurotoxicity of bromazepam by examining reaction
      times (RT) and contingent negative variations (CNV). SUBJECTS AND METHODS: Using
      a videogame produced in our laboratory for psychophysiological research purposes
      (Car Acquisition), 14 healthy volunteers (9 males) aged between 23 and 42 drove a
      vehicle along a road full of curves (i.e. distractors) while they had to respond
      to imperative stimuli (i.e. orders to press the button on the joystick) that were
      preceded by warnings (S1-S2-RM paradigm with distractor). We compared RT,
      amplitudes and latencies of the CNV at each of the three electrodes on the median
      line (Fz, Cz and Pz) one hour after random, double-blind and crossed
      administration of placebo (P), 3 mg of bromazepam (B3) or 6 mg of bromazepam (B6)
      on different days. STATISTICS: one-way ANOVA and Post Hoc Scheffe. RESULTS: No
      significant differences were observed in the RT. At Pz, the CNV amplitudes
      displayed significant differences for P, B3 and B6 (p = 0.006), and also for B3
      and B6 (p = 0.018), with B6 > B3 = P. At Fz, a non-significant tendency (p =
      0.074) suggested a difference between the latencies, shorter in B6 than in B3 (p
      = 0.098), both equivalent to placebo. The mean amplitudes ranged between 2.4 and
      5.9 microV. CONCLUSIONS: Behavioural and neurophysiological neurotoxicity was
      insignificant one hour after administration of a single 3 or 6 mg dose of
      bromazepam in healthy young adults. Low mean amplitudes were compatible with the
      interference from distractors and did not result in floor effect.

PMID- 17006860
TI  - [From neuronal recovery to the reorganisation of neuronal circuits: a review of
      the functions of sleep].
AB  - AIM: To analyse the data and concepts that have been produced in relation to one
      of the functions that have been suggested for sleep, namely, neuronal recovery.
      DEVELOPMENT: Sleep is a state of consciousness that is different to that of
      arousal. Mammals devote an important part of their lives to sleeping; for
      example, as humans, we sleep for a third of our lives, but why do we spend so
      much time in a state where we lose contact with our surroundings? What would
      happen if we didn't sleep? Total sleep deprivation alters cognitive processes
      such as memory or attention, and if this deprivation is prolonged, the individual
      deteriorates and dies. It has been suggested that sleep provides the organism
      with time to recover from the wear and tear that occurs during the waking state
      and, given that the first effects of the absence of sleep are seen to affect
      processes that are directly dependent on the brain, it has been claimed that its
      main purpose is to allow neuronal recovery. In this work we analyse some of the
      studies on the effects of total sleep deprivation in humans and rats, as well as
      the relationship between sleep and the neurotrophin system, which promotes
      neuronal survival and recovery. Finally, the latest theories about the function
      of sleep are discussed. CONCLUSIONS: Neuron recovery is not the ultimate purpose
      of sleep; rather it is to allow for maintenance and reorganisation of neuronal
      circuits, including new synapse formation, which enables existing neuronal
      networks to be modified by the effect of experience, and all this makes it
      possible for the brain to work properly and to adapt itself to the environment.

PMID- 17006861
TI  - [Diseases of the human mitochondrial oxidative phosphorylation system].
AB  - AIM: The diseases of the oxidative phosphorylation system consist of a group of
      disorders originated by a deficient synthesis of adenosine triphosphate (ATP).
      These diseases are increasingly being diagnosed among patients with multisystemic
      disorders. Mitochondrial deoxyribonucleic acid (mtDNA) mutations are usually
      maternally inherited, but they also can be sporadic or secondary to nuclear
      mutations, that are inherited in a Mendelian mode, or due to environmental
      hazards. In this review we will update, from a genetic point of view, the
      knowledge on human mitochondrial diseases, remarking the difficulties to study
      these pathologies. DEVELOPMENT: To mirror these difficulties, we will use
      selected examples of mutations in the mitochondrial genome, and review recent
      advances on mitochondrial pathology due to mutations in the nuclear genes
      codifying for mitochondrial proteins that participate in a good performance of
      the oxidative phosphorylation system. CONCLUSIONS: Sequencing of the complete
      human mtDNA should be part of the basic profile in the study of mitochondrial
      diseases. Due to the increasing number of nuclear genes involved in the oxidative
      phosphorylation system performance, their analysis should be based on solid
      biochemical clues.

PMID- 17006862
TI  - [Good practice guidelines for the treatment of autistic spectrum disorders].
AB  - INTRODUCTION: Due to the inexistence of an aetiology-based intervention for
      autistic spectrum disorders (ASD) families and professionals are exposed to
      diverse and sometimes conflictive recommendations when they have to decide the
      most adequate alternative for treatment. AIM: To elaborate treatment guidelines
      agreed by consensus at the ASD Study Group of the (National) Institute of Health
      Carlos III. DEVELOPMENT: Information about treatment of ASD was searched and
      gathered through available evidence based medical (EBM) databases. The data
      generated was complemented with practice parameters published elsewhere, reports
      from prestigious international institutions, focus oriented searches in PubMed
      and, finally, the opinion and experience of a multidisciplinary Study Group with
      extensive experience in treating ASD in Spain. Most popular treatment methods
      were reviewed as well as the common elements to be considered in successful
      support programs. CONCLUSION: No simple treatment algorithm can be produced at
      this time, and the level of available evidence based recommendations are in the
      weaker degrees of EBM classifications. Nevertheless, there is widespread
      agreement to stress that education, with special incidence in the development of
      communication and social competence, with the addition of community support are
      the main means of treatment. They can be complemented, depending on individual
      needs, with medication, behavioural approaches and cognitive-behavioural therapy
      for associated psychological problems in persons with higher cognitive level.
      Support to families and community empowerment are essential elements for the
      quality of life of persons with ASD.

PMID- 17006863
TI  - [Proton spectroscopy in mild cognitive impairment].

PMID- 17006864
TI  - [Pseudotumoral demyelinating brain lesions with neuropathological confirmation].

PMID- 17006865
TI  - [Paraparesis following anaesthesia with nitrous oxide].

PMID- 17006866
TI  - [Progression of botulinum toxin dosage in focal spasticity and cervical
      dystonia].

PMID- 17006867
TI  - [Regarding generic antiepileptic drugs].

PMID- 17006869
TI  - Calculation of the dependence of homo- and heteronuclear 3J and 2J scalar
      couplings for the determination of the 2'-hydroxy conformation in RNA.

PMID- 17006870
TI  - Total synthesis and antitumor activity of ZK-EPO: the first fully synthetic
      epothilone in clinical development.

PMID- 17006871
TI  - Validation of the Spanish version of the EURO-D scale: an instrument for
      detecting depression in older people.
AB  - OBJECTIVE: To standardize the EURO-D scale as a method for detecting depression
      in Spanish older people. METHODS: In a first phase, a sample of 1080 community
      older people was assessed with the GMS-AGECAT by lay interviewers. In a second
      phase, all the probable cases and a similar number of randomly selected probable
      non-cases were assessed using DSM-III-R diagnosis by psychiatrists. To test
      reliability, internal consistency with the Cronbach alpha coefficient and test
      retest reliability (Kappa value) were obtained. Validity, sensitivity and
      specificity, predictive values, Receiver Operating Characteristic (ROC) curve,
      and Specific Likelihood Ratios (SSLR) were calculated. RESULTS: A high internal
      consistency was obtained in both phases of the study (alpha = 0.75; alpha = 0.79,
      respectively). Test-retest reliability was acceptable (weighted kappa = 0.60).
      For the prediction of DSM-III-R diagnosis validity coefficients (cut-off point
      3/4) were: sensitivity 91.8%, specificity 76.6% and area under the ROC curve 0.92
      [95% Confidence Intervals (0.89-0.95)]. Illiteracy and cognitive difficulties had
      a small negative effect on the performance of the scale. CONCLUSIONS: The EURO-D
      scale is a reliable and valid instrument for detecting probable cases of
      depression in older people in Spain. Illiteracy and cognitive difficulties should
      be considered when interpreting the results.

PMID- 17006872
TI  - A systematic review of intervention studies about anxiety in caregivers of people
      with dementia.
AB  - BACKGROUND: There is considerable literature on managing depression, burden and
      psychological morbidity in caregivers of people with dementia (CG). Anxiety has
      been a relatively neglected outcome measure but may require specific
      interventions. OBJECTIVE: To synthesise evidence regarding interventions that
      reduce anxiety in CGs. METHODS: Twenty-four studies met our inclusion criteria.
      We rated the methodology of studies, and awarded grades of recommendation (GR)
      for each type of intervention according to Centre for Evidence Based Medicine
      guidelines, from A (highest level of evidence) to D. RESULTS: Anxiety level was
      the primary outcome measure in only one study and no studies were predicated on a
      power calculation for anxiety level. There was little evidence of efficacy for
      any intervention. The only RCT to report significantly reduced anxiety involved a
      CBT and relaxation-based intervention specifically devised to treat anxiety, and
      there was preliminary evidence (no randomised controlled trials) that caregiver
      groups involving yoga and relaxation without CBT were effective. There was grade
      B evidence that behavioural management, exercise therapies and respite were
      ineffective. LIMITATIONS: Many interventions were heterogeneous, so there is some
      overlap between groups. Lack of evidence of efficacy is not evidence of lack of
      efficacy. CONCLUSIONS: CBT and other therapies developed primarily to target
      depression did not effectively treat anxiety. Good RCTs are needed to
      specifically target anxiety which might include relaxation techniques. Some of
      the interventions focussed on reducing contact with the care recipients but
      caregivers may want to cope with caring and preliminary evidence suggests
      strategies to help CGs manage caring demands may be more effective.

PMID- 17006873
TI  - Cognitive and psychiatric predictors of medical treatment adherence among older
      adults in primary care clinics.
AB  - OBJECTIVES: Medical treatment non-adherence among older adults is common and
      represents a significant public health care concern. Treatment non-adherence has
      been associated with a number of factors in older adults; however few studies
      have delineated the role of cognition and psychiatric status. PARTICIPANTS: Data
      were collected from 212 ethnically diverse older primary care patients as part of
      a larger study. MEASUREMENTS: Cognitive status was evaluated with the Mattis
      Dementia Rating scale (DRS). Psychiatric status was evaluated using the Geriatric
      Depression Scale (GDS) and the Beck Anxiety Inventory (BAI). Treatment adherence
      was assessed by the total number of missed healthcare appointments and by
      physician and patient ratings. Physician ratings of patients' understanding of
      medical instructions were also obtained. DESIGN: A series of multiple regression
      analyses were conducted to determine cognitive and psychiatric predictors for
      each measure of treatment adherence. RESULTS: GDS and DRS memory scores were both
      independent predictors of the total number of missed medical appointments,
      F(7,55) = 2.34, p = 0.038. GDS score was also shown to be a significant predictor
      of physician ratings of patients' understanding of medical instructions, F(7,33)
      = 0.89, p = 0.031. Neither cognitive performance nor psychiatric status was
      associated with patient or physician ratings of treatment adherence. CONCLUSIONS:
      Measures of cognitive functioning and depression severity were supported as
      predictors of objective measures of treatment adherence but they were not
      associated with physician or patient ratings of adherence. Patient depression may
      influence physician ratings of patients' comprehension of medical instructions.

PMID- 17006874
TI  - Specific symptomatic changes following donepezil treatment of Alzheimer's
      disease: a multi-centre, primary care, open-label study.
AB  - BACKGROUND: Standard measurement scales used in anti-dementia trials may not
      capture symptomatic changes recognized by clinicians and caregivers. We studied a
      symptom checklist, completed separately by caregivers and by clinicians, to
      identify patterns of change associated with donepezil treatment. METHODS: In a
      multi-centre, 6-month, open-label study of 101 primary care patients, changes in
      a 19-symptom checklist were assessed in relation to changes in standardized
      scales of cognition, activities of daily living, behavior, and caregiver burden.
      RESULTS: Three symptoms were reported in more than 80% of patients by both
      clinicians and caregivers: problems in remembering, (97%), temporal orientation
      (89%), and repetitiveness (85%). Five others overlapped on each of the clinician
      and caregiver 'top ten', including cognitive activation, spatial orientation,
      leisure, attention, and apathy. Clinicians reported that symptoms did not improve
      in 38 patients, whereas there was some improvement in 43, and improvement in most
      symptoms in 20. Caregivers reported that symptoms did not improve in 55 patients,
      whereas 27 and 19 patients showed some and most symptoms improving respectively.
      Patients with the greatest symptomatic improvement also improved most on the ADAS
      Cog and the other standardized measures, whereas no improvement (or decline) in
      each standardized measure was observed in people whose symptoms worsened or did
      not improve. CONCLUSION: A symptom checklist allowed clinically meaningful
      profiles to be identified, but revealed different estimates of response between
      clinicians and caregivers. Both agreed that improved executive function was the
      most common response. A symptom checklist can help translate between standard
      measures and everyday practice.

PMID- 17006875
TI  - A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride
      (Aricept) for reducing the incidence of postoperative delirium after elective
      total hip replacement.
AB  - OBJECTIVES: This was a pilot, phase 2a study to assess methodological feasibility
      and the safety and efficacy of donepezil in preventing postoperative delirium
      after elective total hip replacement surgery in older people without pre-existing
      dementia. The hypothesis was that donepezil would reduce the incidence of
      postoperative delirium. METHODS: A double blind, placebo controlled, parallel
      group randomized trial was undertaken. Patients were block randomized pre
      operatively to receive placebo or donepezil 5 mg immediately following surgery
      and every 24 h thereafter for a further three days. The main outcome was the
      incidence of delirium (using the Delirium Symptom Interview). The secondary
      outcome was length of hospital stay. RESULTS: Thirty-three patients (mean age 67
      years; 17 males, 16 females) completed the study (19 donepezil, 14 placebo).
      Donepezil was well tolerated with no serious adverse events. Postoperative
      delirium occurred in 21.2% of subjects. Donepezil did not significantly reduce
      the incidence of delirium. The unadjusted risk ratio (donepezil vs placebo) for
      delirium was 0.29 (95% CI = 0.06,1.30) (chi(2) ([1]) = 3.06; p = 0.08). Mean
      length of hospital stay was 9.9 days for the donepezil group vs 12.1 days in the
      placebo group; difference in means = -2.2 days (95% CI = -0.39,4.78) (t([31]) =
      1.73: p = 0.09). CONCLUSIONS: The experimental paradigm was feasible and
      acceptable. Donepezil did not significantly reduce the incidence of delirium or
      length of hospital stay, however for both outcomes there was a consistent trend
      suggesting possible benefit. The sample size required for a definitive trial (99%
      power, alpha 0.05) would be 95 subjects per arm.

PMID- 17006876
TI  - Survey of the year 2005: literature on applications of isothermal titration
      calorimetry.
AB  - Isothermal titration calorimetry (ITC) can provide a full thermodynamic
      characterization of an interaction. Its usage does not suffer from constraints of
      molecular size, shape or chemical constitution. Neither is there any need for
      chemical modification or attachment to solid support. This ease of use has made
      it an invaluable instrumental resource and led to its appearance in many
      laboratories. Despite this, the value of the thermodynamic parameterization has,
      only quite recently, become widely appreciated. Although our understanding of the
      correlation between thermodynamic data and structural details continues to be
      somewhat naive, a large number of publications have begun to improve the
      situation. In this overview of the literature for 2005, we have attempted to
      highlight works of interest and novelty. Furthermore, we draw attention to those
      works which we feel have provided a route to better analysis and increased our
      ability to understand the meaning of thermodynamic change on binding.

PMID- 17006877
TI  - BAY 41-4109 has multiple effects on Hepatitis B virus capsid assembly.
AB  - Here we report the effect of a heteroaryldihydropyrimidine (HAP) antiviral
      compound, BAY 41-4109, on Hepatitis B virus (HBV) capsid assembly and on
      preformed HBV capsids. The HBV capsid is an icosahedral complex of 120 capsid
      protein dimers. BAY41-4109 inhibits virus production in vivo by a mechanism that
      targets the viral capsid. We found that BAY 41-4109 was able to both accelerate
      and misdirect capsid assembly in vitro. As little as one HAP molecule for every
      five HBV dimers was sufficient to induce formation of non-capsid polymers. Unlike
      the related molecule HAP-1 (Stray et al., Proc. Natl. Acad. Sci. USA 102:8138-43,
      2005), no stable assembly intermediates were observed in assembly reactions with
      BAY 41-4109, indicating that accelerated assembly by BAY 41-4109 was still
      kinetically regulated by the nucleation rate. Preformed capsids were stabilized
      by BAY 41-4109, up to a ratio of one inhibitor molecule per two dimers. However,
      at BAY 41-4109:dimer ratios of 1:1 and greater, capsids were destabilized to
      yield very large non-capsid polymers. These data suggest the existence of two
      functionally distinguishable classes of drug-binding sites on HBV capsids.
      Occupation of the first class of site stabilizes capsid, while binding at the
      second class requires or induces structural changes that cannot be tolerated
      without destabilizing the capsid. Our data suggest that HAP compounds may inhibit
      virus replication by inducing assembly inappropriately and, when in excess, by
      misdirecting assembly decreasing the stability of normal capsids.

PMID- 17006878
TI  - MASCOT HTML and XML parser: an implementation of a novel object model for protein
      identification data.
AB  - Protein identification using MS is an important technique in proteomics as well
      as a major generator of proteomics data. We have designed the protein
      identification data object model (PDOM) and developed a parser based on this
      model to facilitate the analysis and storage of these data. The parser works with
      HTML or XML files saved or exported from MASCOT MS/MS ions search in peptide
      summary report or MASCOT PMF search in protein summary report. The program
      creates PDOM objects, eliminates redundancy in the input file, and has the
      capability to output any PDOM object to a relational database. This program
      facilitates additional analysis of MASCOT search results and aids the storage of
      protein identification information. The implementation is extensible and can
      serve as a template to develop parsers for other search engines. The parser can
      be used as a stand-alone application or can be driven by other Java programs. It
      is currently being used as the front end for a system that loads HTML and XML
      result files of MASCOT searches into a relational database. The source code is
      freely available at http://www.ccbm.jhu.edu and the program uses only free and
      open-source Java libraries.

PMID- 17006879
TI  - Sialic acid and oxidizability of lipid and proteins and antioxidant status in
      patients with coronary artery disease.
AB  - The aim of this study was to investigate the possible relationship between serum
      total sialic acid (TSA) concentration, recently shown to be a cardiovascular risk
      factor, and lipid and protein oxidation and antioxidant status and the severity
      of coronary artery disease (CAD) according to the obstructive vessel number in
      patients. The study was carried out on a total of 200 patients (142 men and 58
      women) who were hospitalized for elective coronary angiographic evaluation with
      complaint of typical angina pectoris. According to the results of angiography,
      150 patients had angiographically proven CAD (CAD group) and 50 patients had a
      history suggestive of angina pectoris but normal coronary angiograms (control
      group). The CAD group was further divided into single-, double- and triple-vessel
      disease groups according to the number of vessels involved. Lipid parameters were
      determined by routine laboratory methods. Plasma malondialdehyde (MDA) and
      vitamin E concentrations were determined by high-performance liquid
      chromatography. TSA and other oxidant and antioxidant parameters were studied
      spectrophotometrically. Our results demonstrated significant increases both in
      TSA levels and in indicators of oxidative stress in the patients with CAD
      compared with the controls. However, antioxidant parameters were decreased in the
      patients with CAD. We found strong positive correlations between TSA and plasma
      MDA, Delta-MDA which represents the degree of oxidative modification of
      apolipoprotein B-containing lipoproteins, serum protein carbonyls and
      apolipoprotein B and weak correlations between TSA and low density lipoprotein
      cholesterol, triacylglycerol, paraoxonase, glutathione peroxidase (GPx), vitamin
      C and vitamin E. In conclusion, TSA is related to markers of lipid and protein
      oxidation, paraoxonase and GPx activities, vitamin C and E levels and the
      severity of CAD.

PMID- 17006880
TI  - The fabrication and evaluation of inline coupling of microdialysis with capillary
      electrophoresis and its application in the determination of blood glucose.
AB  - A novel method of inline coupling of microdialysis (MD) with CE has been
      investigated. A polysulfone MD membrane was in situ prepared at the inlet end of
      the separation capillary, which endued the capillary with an additional function
      of clean-up sampling and made the pretreatment of complex matrices simple. The
      properties of the membrane and its influence on electrophoresis were evaluated.
      The membrane cut off macromolecules and particles efficiently and persistently,
      and changing the components of membrane-casting solution could control the
      molecular weight cutoff of the membrane. Using the capillary having the MD
      membrane in electrophoresis, column efficiency with little reduction was
      achieved. The mixture of chlorpheniramine (CPA) and BSA was used to verify the
      analytical characteristics. Only the peak of CPA appears in the electropherograms
      and the RSDs of migration times and peak areas of CPA were 0.8 and 4.6%,
      respectively. The method was applied for the determination of glucose in human
      blood using an electrochemical detector. Whole blood containing glucose and
      macromolecules was electrokinetically injected directly into the capillary
      without pretreatment, and the concentration of glucose in human blood was 5.5
      mmol/L. Equilibrium dialysis injection is also investigated in this paper. The
      results show that the method may be further used for in vivo sampling to monitor
      the endogenous or exogenous small molecules and their metabolites.

PMID- 17006881
TI  - Capillary electrochromatographic separation of proteins on a column coated with
      titanium dioxide nanoparticles.
AB  - A TiO2 nanoparticle (TiO2 NP)-coated open-tubular column for the capillary
      electrochromatographic separation of proteins is described. The surface chemistry
      of the TiO2 NPs on the inner wall of the fused silica was significantly affected
      by the running buffer. By varying of the phosphate buffer pH, only cathodic EOF
      was indicated. The results showed that TiO2 NPs are existed as a complexed form
      with the buffer ligand. Good separation of conalbumin (ConA), apo-transferrin
      (apoTf), ovalbumin (OVA), and BSA could be achieved with phosphate buffer (40 mM,
      pH 8.0) and an applied voltage of 15 kV. Five peaks of glycoisoforms of OVA were
      observed under these conditions. In comparison with the retention behavior of the
      analytes on the bare fused-silica column, the new column's high resolving power
      seems to be predominantly derived from the ligand exchange of the analytes with
      the phosphate adsorbed onto the TiO2 NPs. The method was also used to separate
      egg-white proteins. Both acidic and basic proteins in egg white were separated in
      a single run. The microheterogeneities of OVA could also be found in it. The
      separation efficiency for the main peak of OVA in egg white was around 10,000
      plates/m.

PMID- 17006882
TI  - Hybrid silica monolithic column for capillary electrochromatography with enhanced
      cathodic electroosmotic flow.
AB  - A hybrid silica monolithic stationary phase for RP CEC was prepared by in situ co
      condensation of (3-mercaptopropyl)-trimethoxysilane (MPTMS),
      phenyltriethoxysilane (PTES), and tetraethoxysilane (TEOS) via a sol-gel process.
      The thiol groups on the surface of the stationary phase were oxidized to sulfonic
      acids by peroxytrifluoroacetic acid. The introduced sulfonic acid moieties on the
      monoliths were characterized by a strong and relatively stable EOF in a broad pH
      range from 2.35 to 7.0 in CEC. Aromatic acids and neutral compounds can be
      simultaneously separated in this column under cathodic EOF. The CEC column
      exhibited a typical RP chromatographic mechanism for neutral compounds due to the
      introduced phenyl groups.

PMID- 17006883
TI  - Stereoselective separations of chiral phosphinic acid pseudodipeptides by CEC
      using silica monoliths modified with an anion-exchange-type chiral selector.
AB  - A nonaqueous CEC method for the simultaneous separation of the four stereoisomers
      of the N-benzyloxycarbonyl phosphinic pseudodipeptide methyl ester
      benzyloxycarbonyl-homophenylalanine Z-hPhepsi(PO2HCH2)Phe-OCH3 as well as of the
      corresponding N-2,4-dinitrophenyl (DNP)-derivative with free C-terminal
      carboxylic group DNP-hPhepsi(PO2HCH2)Phe-OH was developed. For this purpose, a
      monolithic silica capillary column modified with a cinchona alkaloid-derived
      anion-exchange-type chiral selector, namely O-9-(tert-butylcarbamoyl)quinidine
      (tBuCQD) was prepared. The mobile phase composition (ACN/methanol ratio,
      counterion type) was thoroughly optimized to end up with baseline resolution of
      all four stereoisomers with critical resolution of as high as about 2. The CEC
      method proved to be superior over the corresponding HPLC separations primarily
      due to significantly enhanced plate numbers (between 200,000 and 600,000 m(-1) in
      CEC). Diastereoselectivity contributions arising from electrophoretic mobility
      differences of the diastereomers facilitated the separation of the later eluted
      diastereomeric peak pair (peaks III and IV), but had a negative influence on the
      selectivity of the earlier eluted diastereomeric peak pair (peaks I and II). The
      stereoselective CEC assay allowed the assessment of the stereoisomeric purity of
      the individual isomers which were obtained by preparative HPLC on a CHIRALPAK QD
      AX column that is based on the same tBuCQD selector. The present study
      demonstrates that there exist problems which are hard to solve by HPLC, yet can
      be conveniently solved by CEC. Moreover, it was intended to prove by this
      practical application that CEC with monolithic columns is robust enough to be
      used for solving real-life problems.

PMID- 17006884
TI  - Enantioselectivity of basic analytes in CZE enantioseparation under reversed
      polarity mode using sulfated beta-cyclodextrins as chiral selectors: An unusual
      temperature effect.
AB  - Temperature effects on the enantioselectivity of basic analytes in CZE
      enantioseparation were studied under reversed-polarity mode using randomly
      sulfate-substituted beta-CDs (MI-S-beta-CD) as chiral seletors. Two
      catecholamines (epinephrine and isoproterenol) and two structurally related
      compounds (octopamine and norephedrine) were selected as test compounds in an
      electrophoretic system at low pH. The mobility differences between the (+)
      enantiomers and the (-)-enantiomers of the two catecholamines and dopamine at 40
      degrees C are greater than those at 25 degrees C with MI-S-beta-CD, even at a
      concentration as low as 0.3% w/v. Thus the enantioselectivity of these three
      basic analytes increases with increasing temperature. This phenomenon results
      from the inequality of the temperature effect on the mobility of the two
      enantiomers. In contrast, norephedrine behaves differently. The (+)-enantiomers
      of these basic analytes were found to migrate faster than the (-)-enantiomers.
      Consequently, the unusual temperature effect on the enantioselectivity can be
      observed when the mobility difference of the (+)-enantiomer between 40 and 25
      degrees C is greater than that of the (-)-enantiomer using MI-S-beta-CD at a
      concentration greater than about 0.7% w/v for enantioseparation of isoproterenol,
      0.4% w/v for epinephrine, and 0.3% w/v for octopamine. This unusual temperature
      effect offers the advantages to enhance enantioselectivity, to improve
      enantioseparation, and to reduce migration times.

PMID- 17006885
TI  - In-depth study of the electromagnetics of ultrahigh-field MRI.
AB  - In this work, numerical and experimental studies of the transverse
      electromagnetic (TEM) resonator modes at ultrahigh-field (UHF) MRI are performed
      using an in-house finite difference time domain package at 340 MHz and using an 8
      T whole-body MRI system. The simulations utilized anatomically detailed human
      head mesh and a spherical head-sized phantom, while the experiments included an
      electromagnetically equivalent (to simulations) phantom and in vivo human head
      studies. An in-depth look at the homogeneity of the transmit-and-receive fields
      and local and global polarization of the electromagnetic waves inside the cavity
      of the head coil, and also the current distribution obtained on the resonator
      elements, is provided for several coil modes when the coil is empty and loaded.
      Based on the numerical and experimental results, which are in excellent
      agreement, an electromagnetic characterization of loading radio-frequency (RF)
      head coils during a UHF MRI experiment is provided. The possibility of using the
      aforementioned modes for specific types of imaging application is briefly
      reviewed.

PMID- 17006886
TI  - Prediction of chemotherapeutic response of colorectal liver metastases with
      dynamic gadolinium-DTPA-enhanced MRI and localized 19F MRS pharmacokinetic
      studies of 5-fluorouracil.
AB  - Systemic chemotherapy is effective in only a subset of patients with metastasized
      colorectal cancer. Therefore, early selection of patients who are most likely to
      benefit from chemotherapy is desirable. Response to treatment may be determined
      by the delivery of the drug to the tumor, retention of the drug in the tumor and
      by the amount of intracellular uptake, metabolic activation and catabolism, as
      well as other factors. The first aim of this study was to investigate the
      predictive value of DCE-MRI with the contrast agent Gd-DTPA for tumor response to
      first-line chemotherapy in patients with liver metastases of colorectal cancer.
      The second aim was to investigate the predictive value of 5-fluorouracil (FU)
      uptake, retention and catabolism as measured by localized (19)F MRS for tumor
      response to FU therapy. Since FU uptake, retention and metabolism may depend on
      tumor vascularization, the relationship between (19)F MRS and the DCE-MRI
      parameters k(ep), K(trans) and v(e) was also examined (1). In this study, 37
      patients were included. The kinetic parameters of DCE-MRI, k(ep), K(trans) and
      v(e), before start of treatment did not predict tumor response after 2 months,
      suggesting that the delivery of chemotherapy by tumor vasculature is not a major
      factor determining response in first-line treatment. No evident correlations
      between (19)F MRS parameters and tumor response were found. This suggests that in
      liver metastases that are not selected on the basis of their tumor diameter, FU
      uptake and catabolism are not limiting factors for response. The transfer
      constant K(trans), as measured by DCE-MRI before start of treatment, was
      negatively correlated with FU half-life in the liver metastases, which suggests
      that, in metastases with a larger tumor blood flow or permeability surface area
      product, FU is rapidly washed out from the tumor.

PMID- 17006887
TI  - Two new disposable bioreactors for plant cell culture: The wave and undertow
      bioreactor and the slug bubble bioreactor.
AB  - The present article describes two novel flexible plastic-based disposable
      bioreactors. The first one, the WU bioreactor, is based on the principle of a
      wave and undertow mechanism that provides agitation while offering convenient
      mixing and aeration to the plant cell culture contained within the bioreactor.
      The second one is a high aspect ratio bubble column bioreactor, where agitation
      and aeration are achieved through the intermittent generation of large diameter
      bubbles, "Taylor-like" or "slug bubbles" (SB bioreactor). It allows an easy
      volume increase from a few liters to larger volumes up to several hundred liters
      with the use of multiple units. The cultivation of tobacco and soya cells
      producing isoflavones is described up to 70 and 100 L working volume for the SB
      bioreactor and WU bioreactor, respectively. The bioreactors being disposable and
      pre-sterilized before use, cleaning, sterilization, and maintenance operations
      are strongly reduced or eliminated. Both bioreactors represent efficient and low
      cost cell culture systems, applicable to various cell cultures at small and
      medium scale, complementary to traditional stainless-steel bioreactors.

PMID- 17006888
TI  - Expression of bacterial biphenyl-chlorobiphenyl dioxygenase genes in tobacco
      plants.
AB  - Optimized plant-microbe bioremediation processes in which the plant initiates the
      metabolism of xenobiotics and releases the metabolites in the rhizosphere to be
      further degraded by the rhizobacteria is a promising alternative to restore
      contaminated sites in situ. However, such processes require that plants produce
      the metabolites that bacteria can readily oxidize. The biphenyl dioxygenase is
      the first enzyme of the bacterial catabolic pathway involved in the degradation
      of polychlorinated biphenyls. This enzyme consists of three components: the two
      sub-unit oxygenase (BphAE) containing a Rieske-type iron-sulfur cluster and a
      mononuclear iron center, the Rieske-type ferredoxin (BphF), and the FAD
      containing ferredoxin reductase (BphG). In this work, based on analyses with
      Nicotiana benthamiana plants transiently expressing the biphenyl dioxygenase
      genes from Burkholderia xenovorans LB400 and transgenic Nicotiana tabacum plants
      transformed with each of these four genes, we have shown that each of the three
      biphenyl dioxygenase components can be produced individually as active protein in
      tobacco plants. Therefore, when BphAE, BphF, and BphG purified from plant were
      used to catalyze the oxygenation of 4-chlorobiphenyl, detectable amounts of 2,3
      dihydro-2, 3-dihydroxy-4'-chlorobiphenyl were produced. This suggests that
      creating transgenic plants expressing simultaneously all four genes required to
      produce active biphenyl dioxygenase is feasible.

PMID- 17006889
TI  - Expansion of mouse embryonic stem cells on microcarriers.
AB  - Embryonic stem (ES) cells have been shown to differentiate in vitro into a wide
      variety of cell types having significant potential for tissue regeneration.
      Therefore, the operational conditions for the ex vivo expansion and
      differentiation should be optimized for large-scale cultures. The expansion of
      mouse ES cells has been evaluated in static culture. However, in this system,
      culture parameters are difficult to monitor and scaling-up becomes time
      consuming. The use of stirred bioreactors facilitates the expansion of cells
      under controlled conditions but, for anchorage-dependent cells, a proper support
      is necessary. Cytodex-3, a microporous microcarrier made up of a dextran matrix
      with a collagen layer at the surface, was tested for its ability to support the
      expansion of the mouse S25 ES cell line in spinner flasks. The effect of inocula
      and microcarrier concentration on cell growth and metabolism were analyzed.
      Typically, after seeding, the cells exhibited a growth curve consisting of a
      short death or lag phase followed by an exponential phase leading to the maximum
      cell density of 2.5-3.9 x 10(6) cells/mL. Improved expansion was achieved using
      an inoculum of 5 x 10(4) cells/mL and a microcarrier concentration of 0.5 mg/mL.
      Medium replacement allowed the supply of the nutrients and the removal of waste
      products inhibiting cell growth, leading to the maintenance of the cultures in
      steady state for several days. These conditions favored the preservation of the
      S25 cells pluripotent state, as assessed by quantitative real-time PCR and
      immunostaining analysis.

PMID- 17006890
TI  - Haplotype matching is not an essential requirement to achieve remyelination of
      demyelinating CNS lesions.
AB  - Transplantation of oligodendrocyte precursor cells (OPCs) results in efficient
      remyelination in animal models of demyelination. However, the experiments so far
      undertaken have not addressed the need for tissue-type matching to achieve graft
      mediated remyelination. Examination of MHC expression (main determinant of
      allograft rejection) by OPCs showed nondetectable levels under standard culture
      conditions and upregulation of MHC Class I expression only upon exposure to
      interferon gamma. We therefore hypothesized that MHC matching of OPC grafts may
      not be crucial to achieve transplant-mediated remyelination. Transplant
      experiments performed using a nonself repairing toxin-induced demyelination model
      showed that, similarly to allogeneic neurons, survival of allogeneic
      oligodendrocyte lineage cells is influenced by donor-host haplotype combination
      and graft composition. Transplantation of allogeneic mixed glial cell cultures
      resulted in remyelination failure by 1 month postengraftment due to a rejection
      response targeting both myelinating oligodendrocytes and OPCs, suggesting that
      inflammation-induced upregulation of OPC MHC I expression results in
      susceptibility to cytotoxic T cell attack. In contrast, remyelination persisted
      for at least 2 months following transplantation of OPC-enriched cultures whose
      overall MHC expression level was significantly decreased. While OPC-enriched
      preparations elicited delayed type hypersensitivity responses in hosts sensitized
      to alloantigens, allografting of such preparations into a central nervous system
      demyelinating lesion did not result in recipient priming. We conclude that while
      allografted oligodendrocyte lineage cells become targets of a graft rejection
      response once this response has been initiated, transplantation of OPC-enriched
      preparations can evade priming against alloantigens and graft rejection. This
      finding indicates that close tissue matching may not be an essential requirement
      for successful transplant-mediated remyelination.

PMID- 17006892
TI  - Calcium signaling in invertebrate glial cells.
AB  - Calcium signaling studies in invertebrate glial cells have been performed mainly
      in the nervous systems of the medicinal leech (Hirudo medicinalis) and the sphinx
      moth Manduca sexta. The main advantages of studing glial cells in invertebrate
      nervous systems are the large size of invertebrate glial cells and their easy
      accessibility for optical and electrophysiological recordings. Glial cells in
      both insects and annelids express voltage-gated calcium channels and, in the case
      of leech glial cells, calcium-permeable neurotransmitter receptors, which allow
      calcium influx as one major source for cytosolic calcium transients. Calcium
      release from intracellular stores can be induced by metabotropic receptor
      activation in leech glial cells, but appears to play a minor role in calcium
      signaling. In glial cells of the antennal lobe of Manduca, voltage-gated calcium
      signaling changes during postembryonic development and is essential for the
      migration of the glial cells, a key step in axon guidance and in stabilization of
      the glomerular structures that are characteristic of primary olfactory centers.

PMID- 17006894
TI  - Functional role of calcium signals for microglial function.
AB  - In this review we summarize mechanisms of Ca(2+) signaling in microglial cells
      and the impact of Ca(2+) signaling and Ca(2+) levels on microglial function. So
      far, Ca(2+) signaling has been only characterized in cultured microglia and thus
      these data refer rather to activated microglia as observed in pathology when
      compared with the resting form found under physiological conditions. Purinergic
      receptors are the most prominently expressed ligand-gated Ca(2+)-permeable
      channels in microglia and control several microglial functions such as cytokine
      release in a Ca(2+)-dependent fashion. A large variety of metabotropic receptors
      are linked to Ca(2+) release from intracellular stores. Depletion of these
      intracellular stores triggers a capacitative Ca(2+) entry. While microglia are
      already in an activated state in culture, they can be further activated, for
      example, by exposure to bacterial endotoxin. This activation leads to a chronic
      increase of [Ca(2+)](i) and this Ca(2+) increase is a prerequisite for the
      release of nitric oxide and cytokines. Moreover, several factors (TNFalpha, IL
      1beta, and IFN-gamma) regulate resting [Ca(2+)](i) levels.

PMID- 17006893
TI  - Calcium signaling in specialized glial cells.
AB  - This article reviews calcium signaling in three specialized types of glial cells:
      Muller cells of the retina, Bergmann glial cells of the cerebellum, and radial
      glial cells of the developing cortex. Muller cells generate spontaneous and
      neuronal activity-evoked increases in Ca(2+). Neuron to Muller cell signaling is
      mediated by neuronal release of ATP and activation of glial P2Y receptors. Muller
      cells, in turn, modulate neuronal excitability and mediate vasomotor responses.
      Bergmann glial cells also generate spontaneous and activity-evoked Ca(2+)
      increases. Neuron to Bergmann glia signaling is mediated by neuronal release of
      nitric oxide, noradrenaline, and glutamate. In Bergmann glia, Ca(2+) increases
      control the structural and functional interactions between these cells and
      Purkinje cell synapses. In the ventricular zone of the developing cortex, radial
      glial cells generate spontaneous Ca(2+) increases that propagate as Ca(2+) waves
      through clusters of neighboring glial cells. These Ca(2+) increases control cell
      proliferation and neurogenesis.

PMID- 17006895
TI  - Neurotransmitter-mediated calcium signalling in oligodendrocyte physiology and
      pathology.
AB  - The function of oligodendrocytes is to myelinate CNS axons. Oligodendrocytes and
      the axons they myelinate are functional units, and neurotransmitters released by
      axons can influence all stages of oligodendrocyte development via calcium
      dependent mechanisms. Some of the clearest functional evidence is for adenosine,
      ATP, and glutamate, which are released by electrically active axons and regulate
      the migration and proliferation of oligodendrocyte progenitor cells and their
      differentiation into myelinating oligodendrocytes. Glutamate and ATP, released by
      both axons and astrocytes, continue to mediate Ca(2+) signaling in mature
      oligodendrocytes, acting via AMPA and NMDA glutamate receptors, and heterogeneous
      P2X and P2Y purinoceptors. Physiological signalling between axons, astrocytes,
      and oligodendrocytes is likely to play an important role in myelin maintenance
      throughout life. Significantly, ATP- and glutamate-mediated Ca(2+) signaling are
      also major components of oligodendrocyte and myelin damage in numerous
      pathologies, most notably ischemia, injury, periventricular leukomalacia, and
      multiple sclerosis. In addition, NG2-expressing glia (synantocytes) in the adult
      CNS are highly reactive cells that respond rapidly to any CNS insult by a
      characteristic gliosis, and are able to regenerate oligodendrocytes and possibly
      neurons. Glutamate and ATP released by neurons and astrocytes evoke Ca(2+)
      signaling in NG2-glia (synantocytes), and it is proposed these regulate their
      differentiation capacity and response to injury. In summary, clear roles have
      been demonstrated for neurotransmitter-mediated Ca(2+) signaling in
      oligodendrocyte development and pathology. A key issue for future studies is to
      determine the physiological roles of neurotransmitters in mature oligodendrocytes
      and NG2-glia (synantocytes).

PMID- 17006896
TI  - Astrocyte calcium elevations: properties, propagation, and effects on brain
      signaling.
AB  - The possibility that astrocytes are involved in brain signaling began to emerge
      in the late 1970s, when it was first shown that astroglia in vitro possess
      numerous receptors for neurotransmitters. It was later demonstrated that cultured
      astroglia and astrocytes in situ respond to neurotransmitters with increases in
      intracellular second messengers, including cyclic AMP and calcium. Astrocyte
      calcium responses have since been extensively studied both in culture and in
      intact tissue. We continue to gather information regarding the various compounds
      able to trigger astrocyte calcium increases, as well as the mechanisms involved
      in their initiation, propagation as a calcium wave within and between astrocytes,
      and effects on signaling within the brain. This review will focus on each of
      these aspects of astrocyte calcium regulation, and attempt to sort out which
      effects are more likely to occur in developmental, pathological, and
      physiological conditions. While we have come far in our understanding of the
      properties or potential of astrocytes' ability to signal to neurons using our
      array of pharmacological tools, we still understand very little regarding the
      level of involvement of astrocyte signaling in normal brain physiology.

PMID- 17006897
TI  - Calcium signaling in Schwann cells at synaptic and extra-synaptic sites: active
      glial modulation of neuronal activity.
AB  - Glial cells are widely dispersed in the central nervous system (CNS) as well as
      in the peripheral nervous system (PNS). In the PNS, perisynaptic Schwann cells
      (PSCs) are the glial cells associated with the pre- and postsynaptic elements of
      the neuromuscular junction (NMJ). They, as other glial cells of the CNS, respond
      to high-frequency motor nerve stimulation with an increase in intracellular
      Ca(2+). In addition to detecting and responding to neurotransmission, PSCs are
      involved in short-term plasticity events where they depress neurotransmission
      through G-protein-dependent mechanisms and potentiate synaptic activity via
      Ca(2+)-dependent mechanisms. In this review, we will discuss evidence that
      outlines the role of PSCs in short- and long-term modulation of synaptic
      activity. We will also emphasize present functional similarities and differences
      in PSC activation at different NMJs. The importance of glial-neural interactions
      along myelinating axons will also be discussed.

PMID- 17006898
TI  - Vesicular transmitter release from astrocytes.
AB  - Astrocytes can release a variety of transmitters, including glutamate and ATP, in
      response to stimuli that induce increases in intracellular Ca(2+) levels. This
      release occurs via a regulated, exocytotic pathway. As evidence of this,
      astrocytes express protein components of the vesicular secretory apparatus,
      including synaptobrevin 2, syntaxin, and SNAP-23. Additionally, astrocytes
      possess vesicular organelles, the essential morphological elements required for
      regulated Ca(2+)-dependent transmitter release. The location of specific
      exocytotic sites on these cells, however, remains to be unequivocally determined.

PMID- 17006899
TI  - Neuronal precursors within the adult rat subventricular zone differentiate into
      dopaminergic neurons after substantia nigra lesion and chromaffin cell
      transplant.
AB  - Neurogenesis in the adult mammalian brain continues in the subventricular zone
      (SVZ). Neuronal precursors from the SVZ migrate along the rostral migratory
      stream to replace olfactory bulb interneurons. After the destruction of the nigro
      striatal pathway (SN-lesion), some SVZ precursors begin to express tyrosine
      hydroxylase (TH) and neuronal markers (NeuN). Grafting of chromaffin cells (CCs)
      into the denervated striatum increases the number of TH+ cells (SVZ TH+ cells;
      Arias-Carrion et al., 2004). This study examines the functional properties of
      these newly differentiating TH+ cells. Under whole-cell patch-clamp, most SVZ
      cells recorded from lesioned and grafted animals (either TH+ or TH-) were non
      excitable. Nevertheless, a small percentage of SVZ TH+ cells had the
      electrophysiologic phenotype of mature dopaminergic neurons and showed
      spontaneous postsynaptic potentials. Dopamine (DA) release was measured in SVZ
      and striatum from both control and SN-lesioned rats. As expected, 12 weeks after
      SN lesion, DA release decreased drastically. Nevertheless, 8 weeks after CCs
      graft, release from the SVZ of SN-lesioned rats recovered, and even surpassed
      that from control SVZ, suggesting that newly formed SVZ TH+ cells release DA.
      This study shows for the first time that in response to SN-lesions and CC grafts
      neural precursors within the SVZ change their developmental program, by not only
      expressing TH, but more importantly by acquiring excitable properties of mature
      dopaminergic neurons. Additionally, the release of DA in a Ca(2+)-dependent
      manner and the attraction of synaptic afferents from neighboring neuronal
      networks gives further significance to the overall findings, whose potential
      importance is discussed.

PMID- 17006901
TI  - Molecular determinants of D-serine-mediated gliotransmission: from release to
      function.
AB  - Since the late 80s, it is recognized that functional activation of N-methyl D
      aspartate receptors (NMDARs) requires the binding of both glutamate and glycine.
      However, the surprising discovery that the wrong isomer of serine, D-serine, is
      present in mammals has profoundly challenged this dogmatic model of NMDARs
      activation. Indeed, there are accumulating evidence indicating that D-serine is
      the endogenous ligand for the glycine modulatory binding site in many brain
      areas. D-Serine is synthesized in glial cells by serine racemase (SR) and
      released upon activation of glutamate receptors. Here, we will provide an
      overview of recent findings on the molecular and cellular mechanisms involved in
      the synthesis and release of this gliotransmitter. We will also emphasize the
      function of this novel messenger in regulating synaptic excitatory transmission
      and plasticity in different brain areas. Because it fulfils all criteria for a
      gliotransmitter, D-serine regulatory action on glutamatergic transmission further
      illustrates the emerging concept of the "tripartite synapse".

PMID- 17006900
TI  - Astrocyte calcium waves: what they are and what they do.
AB  - Several lines of evidence indicate that the elaborated calcium signals and the
      occurrence of calcium waves in astrocytes provide these cells with a specific
      form of excitability. The identification of the cellular and molecular steps
      involved in the triggering and transmission of Ca(2+) waves between astrocytes
      resulted in the identification of two pathways mediating this form of
      intercellular communication. One of them involves the direct communication
      between the cytosols of two adjoining cells through gap junction channels, while
      the other depends upon the release of "gliotransmitters" that activates membrane
      receptors on neighboring cells. In this review we summarize evidence in favor of
      these two mechanisms of Ca(2+) wave transmission and we discuss that they may not
      be mutually exclusive, but are likely to work in conjunction to coordinate the
      activity of a group of cells. To address a key question regarding the functional
      consequences following the passage of a Ca(2+) wave, we list, in this review,
      some of the potential intracellular targets of these Ca(2+) transients in
      astrocytes, and discuss the functional consequences of the activation of these
      targets for the interactions that astrocytes maintain with themselves and with
      other cellular partners, including those at the glial/vasculature interface and
      at perisynaptic sites where astrocytic processes tightly interact with neurons.

PMID- 17006902
TI  - P2X(7) receptors: properties and relevance to CNS function.
AB  - Among seven members of P2X ionotropic receptors activated by extracellular ATP,
      the P2X(7) subtype is unique in that it can function as a cation channel, a
      nonselective pore, or even a signaling complex coupled with multiple downstream
      components. Several roles of P2X(7) receptors have been described in CNS cells in
      the past decade, including release of cytokines and transmitters, modulation of
      presynaptic transmitter release, and activation of multiple signaling pathways.
      The finding that P2X(7) pores may directly mediate efflux of cytosolic glutamate,
      GABA, and ATP in glial cells is particularly interesting, as it provides a novel
      mechanism of glial transmitter release that may play important roles not only in
      physiological intercellular communication but also in pathological neural injury.

PMID- 17006904
TI  - Functional connexin "hemichannels": a critical appraisal.
AB  - "Hemichannels" are defined as the halves of gap junction channels (also termed
      connexons) that are contributed by one cell; "hemichannels" are considered to be
      functional if they are open in nonjunctional membranes in the absence of pairing
      with partners from adjacent cells. Several recent reviews have summarized the
      blossoming literature regarding functional "hemichannels", in some cases
      encyclopedically. However, most of these previous reviews have been written with
      the assumption that all data reporting "hemichannel" involvement really have
      studied phenomena in which connexons actually form the permeability or
      conductance pathway. In this review, we have taken a slightly different approach.
      We review the concept of "hemichannels", summarize properties that might be
      expected of half gap junctions and evaluate the extent to which the properties of
      presumptive "hemichannels" match expectations. Then we consider functions
      attributed to hemichannels, provide an overview of other channel types that might
      fulfill similar roles and provide sets of criteria that might be applied to
      verify involvement of connexin hemichannels in cell and tissue function. One firm
      conclusion is reached. The study of hemichannels is technically challenging and
      fraught with opportunities for misinterpretation, so that future studies must
      apply rigorous standards for detection of hemichannel expression and function. At
      the same time there are reasons to expect surprises, including the possibility
      that some time honored techniques for studying gap junctions may prove unsuitable
      for detecting hemichannels. We advise hemichannel researchers to proceed with
      caution and an open mind.

PMID- 17006903
TI  - Anion channels in astrocytes: biophysics, pharmacology, and function.
AB  - The chloride/anion channels that have been so far identified in cultured
      astrocytes and those that have been confirmed in situ by a combination of mRNA
      identification, immunocytochemistry, and biophysical studies are reviewed. It is
      emphasized that we are just beginning to describe such channels and analyze their
      functions in astrocytes. The best-studied anion channels studied so far are those
      known as volume-regulated anion channels (VRACs). These, as for most channels,
      have been mainly studied in cultured astrocytes, but some correlative studies
      have been done in situ, because these channels have been emphasized as release
      routes for transmitters; namely, excitatory amino acids and ATP. They are
      activated by cell shape changes and cell swelling, and the release of amino acids
      and ATP and chloride currents, measured by whole cell clamping, by these
      processes has been well described, as is also their activation by low
      concentrations of extracellular ATP. However, the identity of these channels in
      astrocytes, as in all other cells, remains elusive. The potential involvement of
      VRACs in pathological states such as stroke, metastasis, and spreading depression
      is also discussed.

PMID- 17006905
TI  - Hepatitis C virus E2 and CD81 interaction may be associated with altered
      trafficking of dendritic cells in chronic hepatitis C.
AB  - Dendritic cells (DC) are crucially involved in the induction of immune responses;
      however, reports on DC functions in chronic hepatitis C are controversial.
      Function of DC includes proper cell trafficking between sites of infection and
      lympho-cellular compartments. Thus, we analyzed DC compartmentalization and
      changes in DC migration in hepatitis C virus (HCV)-infected patients. We found
      significantly lower numbers of circulating BDCA1+ and BDCA2+ DC in HCV(+)
      patients (n = 20) than in healthy controls (n = 12) (P < .05). Analyzing liver
      samples from HCV(+) patients (n = 15), HCV(-) controls (n = 15), and disease
      controls (n = 10), we demonstrated chronic hepatitis C to be associated with
      intrahepatic DC enrichment (P < .05). In vitro studies indicated that HCV E2
      induced secretion of RANTES efficiently attracts CCR5(+) immature DC. Incubation
      of DC with sera derived from HCV(+) patients made DC unresponsive to CCL21, the
      chemokine recruiting DC to lymphoid tissues for T cell priming. Unlike attraction
      of CCR5+ DCs via RANTES, direct inhibition of DC migration in response to CCL21
      was specific for patients with chronic hepatitis C and could be attributed to
      interaction of HCV E2 with CD81 on DC. In conclusion, migration of DC is markedly
      affected by interaction of HCV E2 with CD81. Failure of DC to recirculate to
      lymphoid tissue may be critically involved in impaired T cell priming during HCV
      infection.

PMID- 17006906
TI  - Interleukin-29 uses a type 1 interferon-like program to promote antiviral
      responses in human hepatocytes.
AB  - Interleukin-28A (IL-28A), IL-28B and IL-29 are a family of class II cytokines
      that stimulate antiviral responses through a heterodimeric receptor that is
      distinct from the type I interferon (IFN) receptor. To better understand how this
      newly described family of cytokines regulates the antiviral state, we compared
      various cellular responses elicited by IL-29 and IFN-alpha. Here we show that
      these cytokines stimulate similar patterns of signal transducer and activator of
      transcription 1 (STAT-1), -2, -3, and -5 phosphorylation and nearly identical
      patterns of gene expression when analyzed in two distinct cell types by
      microarray analysis. Interestingly, the IL-29 receptor is preferentially
      expressed on primary hepatocytes within normal liver and pegylated forms of IL-29
      and IFN-alpha induced equivalent 2'5' oligoadenylate synthetase (OAS) and MX1
      gene expression in this cell type. Pegylated IL-29 also produced a significant
      reduction in human hepatitis B and hepatitis C viral load in vitro and reduced
      the cytopathic effect caused by the fully replicating flavivirus, West Nile
      virus. In conclusion, IL-29 and IFN-alpha stimulate identical antiviral responses
      despite their utilization of different receptors. This fact, combined with
      significant receptor expression in hepatitis virus-infected livers, suggests that
      IL-29 may have therapeutic value against chronic viral hepatitis in human
      patients.

PMID- 17006907
TI  - Favorable effect of adefovir on the number and functionality of myeloid dendritic
      cells of patients with chronic HBV.
AB  - In patients with chronic hepatitis B virus (HBV), 2 predominant precursor
      dendritic cell (DC) subtypes, the myeloid dendritic cell (mDC) and the
      plasmacytoid dendritic cell (pDC), were recently found to be functionally
      impaired. HBV DNA was found to be present in the DC subtypes, but no viral
      replication could be detected. The question remains whether simply the presence
      of the virus and viral proteins causes this dysfunction of DCs. To address this
      issue, the effect of viral load reduction resulting from treatment with the
      nucleotide analogue adefovir dipivoxil on the number and functionality of
      circulating DCs was studied during 6 months of treatment. Treatment resulted in a
      mean 5 log(10) decrease in the viral load and normalization of alanine
      aminotransferase within 3 months. The number of mDCs, but not of pDCs, increased
      significantly over 6 months of treatment to a level comparable to that of
      uninfected healthy controls. The allostimulatory capacity of isolated and in
      vitro matured mDCs increased significantly after 3 months of treatment.
      Accordingly, mDCs exhibited an increased capacity to produce tumor necrosis
      factor alpha and interleukin-12 after 3-6 months of treatment. There was no
      change in interferon alpha production by pDCs during treatment. In conclusion,
      adefovir treatment results in an improvement in the number and functionality of
      mDCs, but not of pDCs. Our findings provide clues for the reasons why current
      antiviral therapy does not lead to consistently sustained viral eradication.

PMID- 17006908
TI  - Influence of hepatitis B virus genotypes on the intra- and extracellular
      expression of viral DNA and antigens.
AB  - Various genotypes of the hepatitis B virus (HBV) induce liver disease of distinct
      severity, but the underlying virological differences are not well defined. Huh7
      cells were transfected with plasmids carrying 1.24-fold the HBV genome of
      different genotypes/subgenotypes (2 strains each for Aa/A1, Ae/A2, Ba/B2 and D; 3
      each for Bj/B1 and C). HBV DNA levels in cell lysates, determined by Southern
      hybridization, were the highest for C followed by Bj/Ba and D/Ae (P < .01), and
      the lowest for Aa (P < .01), whereas in culture media, they were the highest for
      Bj, distantly followed by Ba/C/D and further by Ae/Aa (P < .01). The
      intracellular expression of core protein was more than 3-fold lower for Ae/Aa
      than the others. Hepatitis B e antigen (HBeAg) was excreted in a trend similar to
      that of HBV DNA with smaller differences. Secretion of hepatitis B surface
      antigen (HBsAg) was most abundant for Ae followed by Aa, Ba, Bj/C and remotely by
      D, which was consistent with mRNA levels. Cellular stress determined by the
      reporter assay for Grp78 promoter was higher for C and Ba than the other
      genotypes/subgenotypes (P < .01). Severe combined immunodeficiency mice
      transgenic for urokinase-type plasminogen activator (uPA/SCID), with the liver
      replaced for human hepatocytes, were inoculated with virions passed in mouse and
      recovered from culture supernatants. HBV DNA levels in their sera were higher for
      C than Ae by 2 logs during 4-7 weeks after inoculation. In conclusion,
      virological differences among HBV genotypes were demonstrated both in vitro and
      in vivo. These differences may influence HBV infections with distinct genotypes
      in clinical and epidemiological settings.

PMID- 17006909
TI  - Modeling hepatic fibrosis in African American and Caucasian American patients
      with chronic hepatitis C virus infection.
AB  - Assessment of histological stage is an integral part of disease management in
      patients infected with the hepatitis C virus (HCV). The aim of this study was to
      develop a model incorporating objective clinical and laboratory parameters to
      estimate the probability of severe fibrosis (i.e., Ishak fibrosis > or = 3) in
      previously untreated African American (AA) and Caucasian American (CA) patients
      with HCV genotype 1. The Ishak fibrosis scores of 205 CA and 194 AA patients
      enrolled in the Viral Resistance to Antiviral Therapy of Chronic Hepatitis C
      study (Virahep-C) were modeled using simple and multiple logistic regression. The
      model was then validated in an independent cohort of 461 previously untreated
      patients with HCV. The distribution of fibrosis scores was similar in the AA and
      CA patients as was the proportion of patients with severe fibrosis (35% vs. 39%,
      P = .47). After accounting for the number of portal areas in the biopsy, patient
      age, serum aspartate aminotransferase, alkaline phosphatase, and platelet count
      were independently associated with severe fibrosis in the overall cohort, and the
      relationship with fibrosis was similar in both the AA and CA subgroups. The area
      under the receiver operating characteristic curve (AUROC) of the Virahep-C model
      (0.837) was significantly better than in other published models (P = .0003). The
      AUROC of the Virahep-C model was 0.851 in the validation population. In
      conclusion, a model consisting of widely available clinical and laboratory
      features predicted severe hepatic fibrosis equally well in AA and CA patients
      with HCV genotype 1 and was superior to other published models. The excellent
      performance of the Virahep-C model in an external validation cohort suggests the
      findings are replicable and potentially generalizable.

PMID- 17006910
TI  - HCV core expression in hepatocytes protects against autoimmune liver injury and
      promotes liver regeneration in mice.
AB  - Hepatitis C virus (HCV) infection causes acute and chronic liver disease often
      leading to liver cirrhosis and hepatocellular carcinoma. Numerous studies have
      shown that despite induction of virus specific immunity, a curative response is
      often not attained; this has led to the hypothesis that HCV genes modulate
      immunity, thereby enabling chronic infections. This study examined the effects on
      immune-mediated liver injury in transgenic mice expressing core protein
      throughout the body and bone marrow chimeras expressing core protein in either
      the lymphoid compartment or liver parenchyma. Presence of core protein in the
      liver parenchyma but not in lymphoid cells protects from autoimmune hepatitis
      induced by mitogen concanavalin A (ConA). Consistent with this observation, core
      transgenic hepatocytes are relatively resistant to death induced by anti-Fas
      antibody and tumor necrosis factor alpha (TNFalpha). This protective effect is
      associated with preferential activation of signal transducer and activation of
      transcription factor 3 (STAT3) versus STAT1 in livers of ConA-injected animals.
      In agreement with this effect of core protein on the Janus kinase (JAK)-STAT
      signaling pathway, transgenic mice accelerate liver regeneration after partial
      hepatectomy but are not protected from hepatocyte death. In conclusion, HCV core
      inhibits STAT1 and stimulates STAT3 activation, which protects infected
      hepatocytes from attack by the cell-mediated immune system and promotes their
      proliferation.

PMID- 17006912
TI  - Hepatobiliary transporters and drug-induced cholestasis.
AB  - Drug-induced liver injury is an important clinical problem with significant
      morbidity and mortality. Whereas for most hepatocellular forms of drug-induced
      hepatic injury the underlying pathophysiological mechanism is poorly understood,
      there is increasing evidence that cholestatic forms of drug-induced liver damage
      result from a drug- or metabolite-mediated inhibition of hepatobiliary
      transporter systems. In addition to their key role in determining hepatic drug
      exposure and clearance, the coordinated action of these transport systems is
      essential for bile formation and the biliary secretion of cholephilic compounds
      and xenobiotics. Any drug-mediated functional disturbance of these processes can
      lead to an intracellular accumulation of potentially harmful bile constituents
      and result in the development of cholestatic liver cell damage. In addition to
      direct drug-mediated inhibition of hepatocellular transport, function of these
      transporters can be altered by pre-existing hepatic disease and genetic factors,
      which contribute to the development of drug-induced cholestasis in susceptible
      individuals. This review summarizes current knowledge about the function of
      hepatobiliary uptake and efflux systems and discusses factors that might
      predispose to drug-induced cholestasis.

PMID- 17006913
TI  - Glutamine: a Trojan horse in ammonia neurotoxicity.
AB  - Mechanisms involved in hepatic encephalopathy still remain to be defined.
      Nonetheless, it is well recognized that ammonia is a major factor in its
      pathogenesis, and that the astrocyte represents a major target of its CNS
      toxicity. In vivo and in vitro studies have shown that ammonia evokes
      oxidative/nitrosative stress, mitochondrial abnormalities (the mitochondrial
      permeability transition, MPT) and astrocyte swelling, a major component of the
      brain edema associated with fulminant hepatic failure. How ammonia brings about
      these changes in astrocytes is not well understood. It has long been accepted
      that the conversion of glutamate to glutamine, catalyzed by glutamine synthetase,
      a cytoplasmic enzyme largely localized to astrocytes in brain, represented the
      principal means of cerebral ammonia detoxification. Yet, the "benign" aspect of
      glutamine synthesis has been questioned. This article highlights evidence that,
      at elevated levels, glutamine is indeed a noxious agent. We also propose a
      mechanism by which glutamine executes its toxic effects in astrocytes, the
      "Trojan horse" hypothesis. Much of the newly synthesized glutamine is
      subsequently metabolized in mitochondria by phosphate-activated glutaminase,
      yielding glutamate and ammonia. In this manner, glutamine (the Trojan horse) is
      transported in excess from the cytoplasm to mitochondria serving as a carrier of
      ammonia. We propose that it is the glutamine-derived ammonia within mitochondria
      that interferes with mitochondrial function giving rise to excessive production
      of free radicals and induction of the MPT, two phenomena known to bring about
      astrocyte dysfunction, including cell swelling. Future therapeutic approaches
      might include controlling excessive transport of newly synthesized glutamine to
      mitochondria and its subsequent hydrolysis.

PMID- 17006914
TI  - Assessing the outcome of nonalcoholic steatohepatitis? It's time to get serious.

PMID- 17006915
TI  - Impaired 11 beta-hydroxysteroid dehydrogenase contributes to renal sodium avidity
      in cirrhosis: hypothesis or fact?
AB  - Exaggerated renal sodium retention with concomitant potassium loss is a hallmark
      of cirrhosis and contributes to the accumulation of fluid as ascites, pleural
      effusion, or edema. This apparent mineralocorticoid effect is only partially
      explained by increased aldosterone concentrations. I present evidence supporting
      the hypothesis that cortisol confers mineralocorticoid action in cirrhosis. The
      underlying molecular pathology for this mineralocorticoid receptor (MR)
      activation by cortisol is a reduced activity of the 11 beta-hydroxysteroid
      dehydrogenase type 2, an enzyme protecting the MR from promiscuous activation by
      cortisol in healthy mammalians.

PMID- 17006916
TI  - Hemodynamic response-guided therapy for prevention of variceal rebleeding: an
      uncontrolled pilot study.
AB  - The clinical usefulness of assessing hemodynamic response to drug therapy in the
      prophylaxis of variceal rebleeding is unknown. An open-labeled, uncontrolled
      pilot trial was performed to evaluate the feasibility and efficacy of using the
      hemodynamic response to pharmacological treatment to guide therapy in this
      setting. Fifty patients with acute variceal bleeding underwent a hepatic venous
      pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and
      nitrates were initiated, and a second HVPG was measured 15 days later. Responder
      patients (> or =20% decrease in HVPG from baseline) were maintained on drugs,
      partial responders (> or =10% and <20%) had banding ligation added to the drugs,
      and nonresponders (<10%) received a transjugular intrahepatic portal-systemic
      shunt (TIPS). Mean follow-up was 22 months. Eight patients (16%) did not receive
      the second HVPG, 6 of them because of early variceal rebleeding. Of the other 42
      patients, 24 were classified as responders (57%); 10 as partial responders (24%),
      who had banding added; and 8 as nonresponders (19%), who received a TIPS.
      Patients with cirrhosis of viral etiology compared to alcoholic cirrhosis tended
      to present more early rebleedings, less response to drugs and needed more TIPS.
      Variceal rebleeding occurred in 22% of all patients but only in 12% of patients
      whose hemodynamic response was assessed. The 3 therapeutic groups were not
      different. In conclusion, using hemodynamic response to pharmacological treatment
      to guide therapy in secondary prophylaxis to prevent variceal bleeding is
      feasible and effectively protects patients from rebleeding. In this context,
      viral cirrhosis seems to present a worse outcome than alcoholic cirrhosis.

PMID- 17006918
TI  - Derivation and validation of a new global method for assessing nutritional status
      in patients with cirrhosis.
AB  - Accurate assessments of nutritional status are difficult to obtain in patients
      with cirrhosis. The aim of this study was to devise and validate a global
      nutritional assessment scheme for use in this patient population. Measures of
      body mass index (BMI) and mid-arm muscle circumference (MAMC) were combined with
      details of dietary intake in a semistructured, algorithmic construct to provide a
      nutritional assessment scheme for use in patients with cirrhosis; evaluated
      individuals were classified as adequately nourished, moderately malnourished (or
      suspected to be), or severely malnourished. There was good interobserver
      agreement in the nutritional categorization of 50 patients with cirrhosis (34
      men, 16 women) using this scheme (kappa = 0.79) and significant associations with
      the contributing objective variables--namely, BMI (Spearman's correlation r = 
      0.78; P < .001) and relative MAMC (r = -0.69; P < .001)--confirming its internal
      validity. There was a significant association between nutritional categorization
      in 20 patients with cirrhosis (10 men, 10 women) and estimates of total body
      protein obtained using a four-component model (r = -0.45; P = .046), confirming
      the external validity of the scheme. Finally, a significant association was found
      between poor nutritional status in 116 patients with cirrhosis (65 men, 51
      women), followed for 14 to 52 months, and shorter subsequent survival (P =
      .0005), confirming the scheme's predictive validity. In conclusion, a global
      assessment scheme has been devised that provides a simple, reproducible, valid,
      and predictive method of assessing nutritional status in patients with cirrhosis.

PMID- 17006917
TI  - Contribution of hepatic adenosine A1 receptors to renal dysfunction associated
      with acute liver injury in rats.
AB  - Acute liver injury is associated with renal insufficiency, whose mechanism may be
      related to activation of the hepatorenal reflex. We previously showed that
      intrahepatic adenosine is involved in activation of the hepatorenal reflex to
      restrict urine production in both healthy rats and in rats with cirrhosis. The
      aim of the present study was to test the hypothesis that activation of
      intrahepatic adenosine receptors is involved in the pathogenesis of the renal
      insufficiency seen in acute liver injury. Acute liver injury was induced by
      intraperitoneal injection of thioacetamide (TAA, 500 mg/kg) in rats. The animals
      were instrumented 24 hours later to monitor systemic, hepatic, and renal
      circulation and urine production. Severe liver injury developed following TAA
      insult, which was associated with renal insufficiency, as demonstrated by
      decreased (approximately 25%) renal arterial blood flow, a lower (approximately
      30%) glomerular filtration rate, and decreased urine production. Further, the
      increase in urine production following volume expansion challenge was inhibited.
      Intraportal, but not intravenous, administration of a nonselective adenosine
      receptor antagonist, 8-phenyltheophylline, improved urine production. To specify
      receptor subtype, the effects of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, an
      adenosine A(1) receptor antagonist) and 3,7-dimethyl-1-propargylxanthine (DMPX,
      an adenosine A(2) receptor antagonist) were compared. Intraportal but not
      intravenous administration of DPCPX greatly improved impaired renal function
      induced by acute liver injury, and this beneficial effect was blunted in rats
      with liver denervation. In contrast, neither intraportal nor intravenous
      administration of DMPX showed significant improvement in renal function. In
      conclusion, an activated hepatorenal reflex, triggered by intrahepatic adenosine
      A(1) receptors, contributed to the pathogenesis of the water and sodium retention
      associated with acute liver injury.

PMID- 17006919
TI  - Significance of circulating endothelial progenitor cells in hepatocellular
      carcinoma.
AB  - This study evaluated the significance of circulating bone marrow-derived
      endothelial progenitor cells (EPCs) in patients with hepatocellular carcinoma
      (HCC), a solid tumor with rich neovasculature. Eighty patients with HCC were
      recruited for the study, and 16 patients with liver cirrhosis and 14 healthy
      subjects were also included for comparison. Blood samples were taken before
      treatment. Total mononuclear cells were isolated from peripheral blood, preplated
      to eliminate mature circulating endothelial cells, and colony-forming units
      (CFUs) formed by circulating EPCs were counted. To validate the CFU scores, FACS
      quantification of EPCs using CD133, VEGFR2, and CD34 as markers was performed in
      30 cases. Our study showed significantly higher mean CFU scores in patients with
      HCC compared to patients with cirrhosis and healthy controls (P = .001 and .009,
      respectively). Furthermore, the CFU scores of patients with HCC positively
      correlated with levels of serum alpha-fetoprotein (r = .303, P = .017), plasma
      VEGF (r = .242, P = .035), and plasma interleukin-8 (IL-8) (r = .258, P = .025).
      Patients with unresectable HCC had higher CFU scores than patients with
      resectable tumors (P = .027). Furthermore, for those who underwent curative
      surgery, higher preoperative CFU scores were observed in patients with recurrence
      within 1 year compared with those who were disease-free after 1 year (P = .013).
      In conclusion, higher circulating levels of EPCs are seen in patients with
      advanced unresectable HCC as compared to patients with resectable HCC or those
      with liver cirrhosis. Our evidence supports the potential use of circulating
      level of EPCs as a prognostic marker in patients with HCC.

PMID- 17006920
TI  - Determinants of the clinical expression of amoxicillin-clavulanate
      hepatotoxicity: a prospective series from Spain.
AB  - Amoxicillin-clavulanate (AC) hepatotoxicity has been reported to exhibit a higher
      predominance of cholestatic types of damage, especially in males. However, the
      determinants of its clinical expression are unknown. This study prospectively
      evaluated the profile of AC hepatotoxicity. Data on all cases of hepatotoxicity
      reported to the Spanish Registry attributed to AC and assessed as definite or
      probable on the Council for International Organizations of Medical Sciences
      (CIOMS) scale were collated and compared to published case series. Hepatotoxicity
      related to amoxicillin-clavulanate was identified in 69 patients (36 males; mean
      age 56 years) representing 14% of all cases of hepatotoxicity submitted to the
      Registry. There was an overall sex distribution and the predominant pattern of
      lesion was hepatocellular (36%) which occurred at a shorter duration of treatment
      (P < .03). Mean time lapse between therapy initiation and jaundice onset was 16
      days. Late onset of symptoms following end of treatment occurred in half the
      cases. Multiple logistic regression analysis identified advancing age as the
      factor associated with the development of cholestatic/mixed type of injury (odds
      ratio for an age interval for 1 year: 1.045 [95% CI = 1.013-1.078; P = .005). An
      unfavorable outcome was seen in 7% of patients. In conclusion, age is the most
      important determinant in the biochemical expression of AC hepatotoxicity; younger
      age is associated with cytolytic damage and shorter treatment duration, whereas
      cholestatic/mixed type of damage is related to older age and prolonged AC
      therapy.

PMID- 17006921
TI  - Effects of clonidine on diuretic response in ascitic patients with cirrhosis and
      activation of sympathetic nervous system.
AB  - The effects of the addition of clonidine to diuretics on the mobilization of
      ascites in the short term (diuretic response and requirement of diuretics) and
      the long term (readmissions for tense ascites and requirement of diuretics) were
      examined in patients with cirrhosis and with increased sympathetic nervous system
      (SNS) activity. We also studied neurohormonal, hemodynamic effects and side
      effects of clonidine and diuretics. Patients were randomized to receive placebo
      (group 1, n = 32) or clonidine (0.075 mg) twice daily (group 2, n = 32) for 3
      months. After 8 days and for 10 days duration, spironolactone (200 mg/day) was
      added in both groups. After this period, the dosages of diuretics were
      individually increased until diuretic response. Responding patients were
      discharged and followed at the outpatient clinic. During the first
      hospitalization, the time needed for diuretic response was shorter in group 2
      than in group 1. The mean requirement for diuretics was significantly higher in
      group 1 than in group 2, and the diuretic complications (hyperkalemia and renal
      impairment) were significantly lower in group 2. Clonidine induced a permanent
      decrease in SNS activity and delayed decrease in renin/aldosterone levels. During
      the follow-up, the time to the first readmission for tense ascites was shorter in
      group 1 than in group 2. Readmissions related to tense ascites or diuretic
      complications were significantly lower in group 2. The mean requirement for
      diuretics was significantly higher in group 1 than in group 2. In conclusion, the
      additional administration of clonidine to diuretics induced an earlier diuretic
      response associated with fewer diuretic requirements and complications.

PMID- 17006922
TI  - Alpha 1-antitrypsin mutations in NAFLD: high prevalence and association with
      altered iron metabolism but not with liver damage.
AB  - Hyperferritinemia, a common feature of nonalcoholic fatty liver disease (NAFLD),
      has been associated with steatohepatitis and fibrosis. Heterozygosity for alpha 1
      antitrypsin (AAT) mutations is a cofactor of liver damage, and AAT influences
      inflammation and iron metabolism. This study evaluated the prevalence of the
      common AAT PiS/PiZ mutants in 353 patients with NAFLD, 195 of whom had
      hyperferritinemia, versus 114 matched controls and their influence on iron
      metabolism and the severity of liver damage in the 212 patients submitted to
      biopsy. PiS and PiZ alleles were searched for by restriction analysis. Thirty
      eight patients (10.8%) carried non-MM genotypes versus 4/114 (3.5%) controls (P =
      .02). Patients carrying AAT mutations had higher ferritin (573 [454-966] vs. 348
      [201-648]; P = .001) with similar transferrin saturation. The difference was more
      evident in males (P < .0001) and significant in patients not carrying HFE
      genotypes associated with iron overload (P = .015). The prevalence of non-MM
      genotypes was higher in patients with hyperferritinemia than in those without
      (28/195, 14% vs. 10/158, 6%, P = .016), and AAT mutations were associated with
      higher prevalence of sinusoidal siderosis (17/27, 63% vs. 70/180, 39%; P = .02),
      and sinusoidal/total iron score (46.3 +/- 38% vs. 25.1 +/- 35%, P = .01).
      Although ferritin was independently associated with fibrosis (P = .047), AAT
      mutations favoring sinusoidal iron deposition did not affect liver damage. In
      conclusion, AAT mutations are associated with hyperferritinemia and sinusoidal
      iron accumulation, but not with more severe liver damage in NAFLD.

PMID- 17006923
TI  - Long-term follow-up of patients with NAFLD and elevated liver enzymes.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated
      liver enzymes in patients of developed countries. We determined the long-term
      clinical and histological courses of such patients. In a cohort study, 129
      consecutively enrolled patients diagnosed with biopsy-proven NAFLD were
      reevaluated. Survival and causes of death were compared with a matched reference
      population. Living NAFLD patients were offered repeat liver biopsy and clinical
      and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years.
      Mortality was not increased in patients with steatosis. Survival of patients with
      nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more
      often died from cardiovascular (P = .04) and liver-related (P = .04) causes.
      Seven patients (5.4%) developed end-stage liver disease, including 3 patients
      with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had
      a negative predictive value of 100% in predicting liver-related complications. At
      follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance.
      Progression of liver fibrosis occurred in 41%. These subjects more often had a
      weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04),
      and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow
      up. In conclusion, NAFLD with elevated liver enzymes is associated with a
      clinically significant risk of developing end-stage liver disease. Survival is
      lower in patients with NASH. Most NAFLD patients will develop diabetes or
      impaired glucose tolerance in the long term. Progression of liver fibrosis is
      associated with more pronounced insulin resistance and significant weight gain.

PMID- 17006924
TI  - Tensin2 variant 3 is associated with aggressive tumor behavior in human
      hepatocellular carcinoma.
AB  - Tensins are a new family of proteins that act as an important link among
      extracellular matrix, actin cytoskeleton, and signal transduction and have been
      implicated in human cancers. Tensin2 was initially identified in a search for new
      tensin family members that share extensive sequence homology with tensin1.
      Tensin2 was highly expressed in liver tissues. A recent study reported that one
      of the splicing variants of tensin2, variant 3, promotes cell migration. In the
      present study, we aimed to elucidate the role of variant 3 in
      hepatocarcinogenesis by assessing the expression of variant 3 mRNA in
      hepatocellular carcinoma (HCC) tissue and ectopically expressing variant 3 in HCC
      cell lines. Analysis of variant 3 expression in human HCC tissue revealed it was
      overexpressed in 46% (23/50) of tumor tissues as compared with the corresponding
      nontumorous livers. High expression of variant 3 was significantly associated
      with venous invasion (P = .037), tumor microsatellite formation (P = .022), and
      tumor nonencapsulation (P = .049). Our ectopic expression study showed that
      variant 3 significantly promoted the cell growth and motility of HCC cells. The
      clonal transfectants of variant 3 were more closely packed and resulted in a
      higher saturation density than in the control vector transfectants. Variant 3
      expression also enhanced the proliferation rate in culture and in vivo
      tumorigenicity in nude mice. In conclusion, we reveal a novel role for variant 3
      in the progression of HCC and suggest the feasibility of elevated variant 3
      expression as a tumor progression marker for HCC.

PMID- 17006925
TI  - Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial.
AB  - Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a
      major clinical problem. This randomized controlled trial evaluated whether
      postoperative adjuvant therapy with oral uracil-tegafur (UFT) prevents recurrence
      of HCC. A total of 160 patients who underwent curative hepatic resection for HCC
      were randomly assigned to receive either 300 mg/day of UFT for 1 year after
      surgery (n = 79, UFT group) or surgery alone (n = 80, control group). The primary
      endpoint was recurrence-free survival, and the secondary endpoint was overall
      survival. Other study variables included liver function and type of recurrence.
      During a median follow-up of 4.8 years (range: 0.5-7.9), recurrence-free survival
      curves in the groups were similar (P = .87). Overall survival was slightly but
      not significantly worse in the UFT group than in the control group (P = .08). The
      rates of recurrence-free and overall survival at 5 years were 29% and 58%,
      respectively, in the UFT group, as compared with 29% and 73%, respectively, in
      the control group. The hazard ratio for recurrence in the UFT group, relative to
      the control, was 1.01 (95% confidence interval: 0.84-1.22, P = .87). The
      proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or
      associated with vascular invasion) was significantly higher in the UFT group
      (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of
      57) (P = .02). In conclusion, our results offer no evidence to support potential
      benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and
      suggest that such treatment may even worsen overall survival.

PMID- 17006926
TI  - Cleavage of cystatin C is not associated with multiple sclerosis.
AB  - Recently, Irani and colleagues proposed a C-terminal cleaved isoform cystatin C
      (12.5 kDa) in cerebrospinal fluid as a marker of multiple sclerosis. In this
      study, we demonstrate that the 12.5 kDa product of cystatin C is formed by
      degradation of the first eight N-terminal residues. Moreover, such a degradation
      is not specific in the cerebrospinal fluid of multiple sclerosis, but rather is
      given by an inappropriate sample storage at -20 degrees C. We conclude that the
      use of the 12.5 kDa product of cystatin C in cerebrospinal fluid might lead to a
      fallacious diagnosis of multiple sclerosis. Preanalytical validation procedure is
      mandatory for proteomics investigations.

PMID- 17006928
TI  - B lineage cells in inflammatory central nervous system.

PMID- 17006927
TI  - Role of neurofilament aggregation in motor neuron disease.
AB  - A major question in the pathogenesis of motor neuron disease is why motor neurons
      are selectively susceptible to mutations in widely expressed gene products.
      Reexamination of motor neuron degeneration due to alterations of neurofilament
      (NF) expression suggests that disruption of assembly with aggregation of the
      light neurofilament (NFL) protein may be an upstream event and contributing
      factor leading to the preferential degeneration of motor neurons. The
      implications of these findings are that aggregation of NFL is not only a
      triggering mechanism to account for the hallmark aggregates of NF protein in
      sporadic and familial forms of amyotrophic lateral sclerosis, but that aggregates
      of NFL may also promote aggregation of wildly expressed proteins that are
      destabilized by missense mutations, such as by mutations in superoxide dismutase
      1 protein. This review examines the potential role of NFs in determining and
      promoting the preferential degeneration of motor neurons in motor neuron disease.
      The underlying premise is that motor neurons are selectively susceptible to
      alterations in NF expression, that alterations in NF expression lead to NF
      aggregates in motor neurons, and that elevated levels of NF aggregates provide a
      favorable microenvironment for the formation of neurotoxic aggregation and
      degeneration of motor neurons.

PMID- 17006929
TI  - Hepatic expression of glutamine synthetase in rats is controlled by STAT5 and TCF
      transcription factors.
AB  - In mammalian liver, high glutamine synthetase (GS) expression is restricted to
      hepatocytes surrounding the terminal venules. The most important enhancer of the
      GS gene is located approximately 2520 base pairs (bp) upstream from the
      transcriptional start point. The nature of the transcription factors that bind to
      the enhancers has remained enigmatic. In this study, we purified nuclear proteins
      binding to the element. Supershift assays and footprint experiments with purified
      protein identified activated STAT5 as a transcription factor binding to a site
      within the enhancer. In addition, a second binding site close to the STAT5 site
      was observed that also binds a protein present in nuclear extracts. Sequence
      analysis indicated that the second site may bind a member of the LEF/TCF
      transcription factor family. Reporter gene assays demonstrate that the STAT5
      binding site mediates enhancement of expression whereas the LEF/TCF site
      functions as a silencer of growth hormone-mediated enhancement in normal
      hepatocytes. LEF/TCF-sites are known to function as silencers in the absence and
      as enhancers in the presence of activated beta-catenin. In conclusion, the GS 5'
      enhancer contains elements important for GS expression in cells carrying an
      activated form of beta-catenin as previously shown in experimentally induced
      hepatocellular carcinomas.

PMID- 17006930
TI  - STAT1 contributes to dsRNA inhibition of liver regeneration after partial
      hepatectomy in mice.
AB  - Increasing evidence suggests that liver regeneration is suppressed in patients
      with chronic HCV infection; however, the underlying mechanisms remain unclear.
      Previously, we demonstrated that injection of the synthetic double-stranded RNA
      (dsRNA) poly I:C to mimic viral infection suppresses liver regeneration in the
      partial hepatectomy (PHx) model, whereby IFN-gamma contributes to the inhibition.
      In this study, we examined the role of the IFN-gamma-activated downstream signal
      (STAT1) and genes (IRF-1, p21(cip1), and SOCS1) in liver regeneration and
      hepatocyte proliferation. Results show that disruption of the STAT1 gene
      abolished poly I:C suppression of liver regeneration and the inhibitory effect of
      poly I:C on liver regeneration was diminished in IRF-1(-/-) and p21(cip1-/-)mice.
      Treatment with IFN-gamma in vitro inhibited cell proliferation of wild-type mouse
      hepatocytes, but not STAT1(-/-) hepatocytes. The inhibitory effect of IFN-gamma
      on cell proliferation was also diminished in IRF-1(-/-) and p21(cip1-/-)
      hepatocytes, but enhanced in SOCS1(-/-) hepatocytes. Hepatocyte proliferation was
      unaffected by treatment with poly I:C alone, but when hepatocytes were co
      cultured with liver lymphocytes, proliferation was inhibited by IFN-gamma/STAT1
      dependent mechanisms. Moreover, in HCV-infected livers with cirrhosis, activation
      of STAT1 was detected and correlated positively with liver injury (elevated serum
      levels of AST) but negatively with hepatocyte proliferation (hepatocyte PCNA and
      Ki-67 positive immunostaining). In conclusion, STAT1 is involved in dsRNA
      suppression of liver regeneration; not only does STAT1 activation contribute to
      liver injury, it may also block liver repair through inhibition of hepatocyte
      proliferation in HCV-infected patients, playing an important role in the
      pathogenesis of disease.

PMID- 17006931
TI  - Oncogene-specific gene expression signatures at preneoplastic stage in mice
      define distinct mechanisms of hepatocarcinogenesis.
AB  - We applied a genome-wide microarray analysis to three transgenic mouse models of
      liver cancer in which targeted overexpression of c-Myc, E2f1, and a combination
      of the two was driven by the albumin promoter. Although gene expression profiles
      in HCC derived in all three transgenic lines were highly similar, oncogene
      specific gene expression signatures were identified at an early dysplastic stage
      of hepatocarcinogenesis. Overexpression of E2f1 was associated with a strong
      alteration in lipid metabolism, and Srebp1 was identified as a candidate
      transcription factor responsible for lipogenic enzyme induction. The molecular
      signature of c-Myc overexpression included the induction of more than 60 genes
      involved in the translational machinery that correlated with an increase in liver
      mass. In contrast, the combined activity of c-Myc and E2f1 specifically enhanced
      the expression of genes involved in mitochondrial metabolism--particularly the
      components of the respiratory chain--and correlated with an increased ATP
      synthesis. Thus, the results suggest that E2f1, c-Myc, and their combination may
      promote liver tumor development by distinct mechanisms. In conclusion,
      determination of tissue-specific oncogene expression signatures might be useful
      to identify conserved expression modules in human cancers.

PMID- 17006933
TI  - Information processing and transmission in glia: calcium signaling and
      transmitter release.

PMID- 17006932
TI  - Transcriptomic and genomic analysis of human hepatocellular carcinomas and
      hepatoblastomas.
AB  - This study analyzed gene expression patterns and global genomic alterations in
      hepatocellular carcinomas (HCC), hepatoblastomas (HPBL), tissue adjacent to HCC
      and normal liver tissue derived from normal livers and hepatic resections. We
      found that HCC and adjacent non-neoplastic cirrhotic tissue have considerable
      overlap in gene expression patterns compared to normal liver. Several genes
      including Glypican 3, spondin-2, PEG10, EDIL3 and Osteopontin are over-expressed
      in HCC vs. adjacent tissue whereas Ficolin 3 is the most consistently under
      expressed gene. HCC can be subdivided into three clusters based on gene
      expression patterns. HCC and HPBL have clearly different patterns of gene
      expression, with genes IGF2, Fibronectin, DLK1, TGFb1, MALAT1 and MIG6 being over
      expressed in HPBL versus HCC. In addition, specific areas of the genome appear
      unstable in HCC, with the same regions undergoing either deletion or increased
      gene dosage in all HCC. In conclusion, a set of specific genes and areas of
      genomic instability are found across the board in liver neoplasia.

PMID- 17006934
TI  - Correlation of paired liver biopsies in morbidly obese patients with suspected
      nonalcoholic fatty liver disease.
AB  - In the absence of surrogate markers, the evaluation of suspected nonalcoholic
      fatty liver disease (NAFLD) is highly dependent on histological examination. The
      extent of sampling variability affecting the reliability of a single liver biopsy
      in patients with suspected NAFLD is poorly characterized. This prospective study
      aimed to correlate precise histological findings in paired biopsies--right and
      left lobe--in the diagnosis of NAFLD in morbidly obese subjects undergoing
      bariatric surgery employing both Brunt and Matteoni classifications and the NAFLD
      Activity Score (NAS). We also aimed to determine whether the composite
      histopathological findings of the two biopsies would improve diagnostic accuracy.
      Consecutive subjects had an intraoperative biopsy from both right and left lobes,
      evaluated and scored in a blinded manner. Intraobserver agreement was also
      assessed. Kappa coefficients of agreement were calculated. Forty-one subjects had
      acceptable biopsies. Agreement for steatosis was excellent and moderate for
      fibrosis. Concordance was only fair for most features of necroinflammation.
      Intraobserver agreement was only moderate for lobular inflammation. Excellent
      agreement was seen for the diagnosis of NASH using Brunt criteria and good
      agreement when using Matteoni and NAS scoring systems. Composite biopsy data
      particularly improved identification of hepatocyte ballooning. The diagnostic
      accuracy also improved substantially when composite features were compared with
      single-sided biopsy features, especially for the Matteoni and NAS scoring
      systems. In conclusion, significant sampling variability occurs in NAFLD,
      particularly for features of necroinflammation. This should be factored into the
      design of clinical trials and studies of the natural history of the disease.

PMID- 17006935
TI  - Comparison of clinical characteristics in episodic and chronic obsessive
      compulsive disorder.
AB  - Our objective in this study was to compare the demographics and clinical
      characteristics of patients with episodic and chronic obsessive-compulsive
      disorder (OCD). We recruited 128 outpatients with a primary diagnosis of OCD
      according to DSM-IV diagnostic criteria. The episodic (n=24) and chronic (n=104)
      OCD patient groups were compared with respect to demographic variables and scores
      from various psychiatric rating scales. The severity of compulsions was found to
      be significantly lower in the episodic OCD group than in the chronic OCD group.
      When the frequency of Axis I disorders was assessed in the two groups, bipolar
      disorder was found to have a significantly higher prevalence rate in the episodic
      OCD group than that in the chronic OCD group. The results of our study point to
      the possibility of an association between a subgroup of OCD with an episodic
      course and bipolar disorder. The evidence of such a relationship, which needs to
      be confirmed in a larger sample, might expand the scope of the clinical
      assessment and therapy of this subgroup of OCD.

PMID- 17006938
TI  - Leptin-mediated neovascularization is a prerequisite for progression of
      nonalcoholic steatohepatitis in rats.
AB  - Nonalcoholic steatohepatitis (NASH) may cause fibrosis, cirrhosis, and
      hepatocellular carcinoma (HCC); however, the exact mechanism of disease
      progression is not fully understood. Angiogenesis has been shown to play an
      important role in the progression of chronic liver disease. The aim of this study
      was to elucidate the role of angiogenesis in the development of liver fibrosis
      and hepatocarcinogenesis in NASH. Zucker rats, which naturally develop leptin
      receptor mutations, and their lean littermate rats were fed a choline-deficient,
      amino acid-defined diet. Both Zucker and littermate rats showed marked
      steatohepatitis and elevation of oxidative stress markers (e.g., thiobarbital
      acid reactive substances and 8-hydroxydeoxyguanosine). In sharp contrast, liver
      fibrosis, glutathione-S-transferase placental form (GST-P)-positive preneoplastic
      lesions, and HCC developed in littermate rats but not in Zucker rats. Hepatic
      neovascularization and the expression of vascular endothelial growth factor
      (VEGF), a potent angiogenic factor, only increased in littermate rats, almost in
      parallel with fibrogenesis and carcinogenesis. The CD31-immunopositive neovessels
      were mainly localized either along the fibrotic septa or in the GST-P-positive
      lesions. Our in vitro study revealed that leptin exerted a proangiogenic activity
      in the presence of VEGF. In conclusion, these results suggest that leptin
      mediated neovascularization coordinated with VEGF plays an important role in the
      development of liver fibrosis and hepatocarcinogenesis in NASH.

PMID- 17006939
TI  - Activation of Wnt/beta-catenin pathway during hepatocyte growth factor-induced
      hepatomegaly in mice.
AB  - Hepatocyte growth factor (HGF) and beta-catenin both play a crucial role in
      stimulating hepatocyte proliferation, but whether these 2 pathways cooperate in
      inducing hepatocyte proliferation is unclear. We have previously reported that
      beta-catenin forms a complex with c-Met (HGF receptor) that undergoes
      dissociation because of beta-catenin tyrosine phosphorylation on stimulation by
      HGF. It is also known that delivery of the human HGF gene cloned in a plasmid
      under a CMV promoter results in hepatomegaly in mice. In addition, recently
      characterized beta-catenin transgenic mice also showed hepatomegaly. The present
      study was based on the hypothesis that HGF-induced hepatomegaly is mediated, at
      least in part, by activation of the Wnt/beta-catenin pathway. Here we report that
      delivery of the human HGF gene delivery in mice led to hepatomegaly via beta
      catenin activation in the liver in 1- and 4-week studies. The mechanisms of beta
      catenin activation in the 1-week study included loss of c-Met-beta-catenin
      association as well as canonical beta-catenin activation, leading to its nuclear
      translocation. In the 4-week study, beta-catenin activation was observed via
      canonical mechanisms, whereas the c-Met-beta-catenin complex remained unchanged.
      In both studies there was an associated increase in the E-cadherin-beta-catenin
      association at the membrane. In addition, we generated liver-specific beta
      catenin knockout mice, which demonstrated significantly smaller livers. HGF gene
      delivery failed to induce hepatomegaly in these beta-catenin conditionally null
      mice. In conclusion, beta-catenin- and HGF-mediated signaling pathways cooperate
      in hepatocyte proliferation, which may be crucial in liver development,
      regeneration following partial hepatectomy, and pathogenesis of hepatocellular
      carcinoma.

PMID- 17006940
TI  - Coagulation disorders and hemostasis in liver disease: pathophysiology and
      critical assessment of current management.
AB  - Normal coagulation has classically been conceptualized as a Y-shaped pathway,
      with distinct "intrinsic" and "extrinsic" components initiated by factor XII or
      factor VIIa/tissue factor, respectively, and converging in a "common" pathway at
      the level of the FXa/FVa (prothrombinase) complex. Until recently, the lack of an
      established alternative concept of hemostasis has meant that most physicians view
      the "cascade" as a model of physiology. This view has been reinforced by the fact
      that screening coagulation tests (APTT, prothrombin time--INR) are often used as
      though they are generally predictive of clinical bleeding. The shortcomings of
      this older model of normal coagulation are nowhere more apparent than in its
      clinical application to the complex coagulation disorders of acute and chronic
      liver disease. In this condition, the clotting cascade is heavily influenced by
      numerous currents and counter-currents resulting in a mixture of pro- and
      anticoagulant forces that are themselves further subject to change with altered
      physiological stress such as super-imposed infection or renal failure. This
      report represents a summary of a recent multidisciplinary symposium held in
      Charlottesville, VA. We present an overview of the coagulation system in liver
      disease with emphasis on the limitations of the current clinical paradigm and the
      need for a critical re-evaluation of the current tenets governing clinical
      practice. With the realization that there is often limited or conflicting data,
      we have attempted to represent diverse opinion and experience from the
      perspectives of both hepatology and hematology beginning with a brief update on
      the physiology of normal coagulation.

PMID- 17006941
TI  - An autoimmune biliary disease mouse model for primary biliary cirrhosis:
      something for everyone.

PMID- 17006943
TI  - The brain permeability-surface product for ammonia.

PMID- 17006944
TI  - Treatment duration in acute hepatitis C: the issue is not solved yet.

PMID- 17006946
TI  - Indomethacin increases liver damage in a murine model of liver injury from alpha
      1-antitrypsin deficiency.
AB  - Homozygous (PIZZ) alpha-1-antitrypsin (alpha(1)-AT) deficiency is associated with
      the development of liver damage in children as well as chronic liver injury and
      hepatocellular carcinoma in adults. The alpha(1)-AT mutant Z gene encodes a
      mutant protein that accumulates in the endoplasmic reticulum of hepatocytes
      rather than being secreted appropriately into serum. Liver injury is caused by
      the accumulation of alpha(1)-AT mutant Z protein in hepatocytes, which triggers
      downstream intracellular injury pathways. However, development of clinical liver
      disease among PIZZ homozygotes is highly variable, suggesting other genetic or
      environmental factors contribute to liver injury. In this study, we tested
      whether nonsteroidal anti-inflammatory drugs (NSAIDs) could be a comorbid factor
      in the development of liver injury in alpha(1)-AT deficiency using the PiZ mouse.
      This mouse model is transgenic for the mutant Z allele of the human alpha(1)-AT
      gene, in which alpha(1)-ATZ expression is regulated by the human promoter
      regulatory sequences. Our results showed that administration of indomethacin to
      PiZ mice resulted in increased hepatic injury, indicated by increased
      hepatocellular proliferation and increased activation of caspase 9. This
      indomethacin-induced injury was associated with activation of IL-6-STAT3
      signaling, increased expression of alpha(1)-AT mRNA, and greater accumulation of
      mutant polymerized alpha(1)-ATZ protein in livers of indomethacin-treated PiZ
      mice compared to vehicle-treated PiZ animals. In conclusion, environmental
      factors, such as exogenous medication administration, can significantly
      potentiate the liver injury associated with alpha(1)-ATZ hepatic accumulation;
      NSAIDs may be especially injurious to patients with alpha(1)-AT deficiency,
      possibly by increasing the expression and accumulation of the hepatotoxic mutant
      protein.

PMID- 17006947
TI  - Comparison of gene expression profiles between Opisthorchis viverrini and non
      Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma.
AB  - Intrahepatic cholangiocarcinoma (ICC) is the second most common primary cancer in
      the liver, and its incidence is highest in the northeastern part of Thailand.
      ICCs in this region are known to be associated with infection with liver flukes,
      particularly Opisthorchis viverrini (OV), as well as nitrosamines from food. To
      clarify molecular mechanisms of ICC associated with or without liver flukes, we
      analyzed gene expression profiles of OV-associated ICCs from 20 Thai patients and
      compared their profiles with those of 20 Japanese ICCs that were not associated
      with OV, by means of laser microbeam microdissection and a cDNA microarray
      containing 27,648 genes. We identified 77 commonly upregulated genes and 325
      commonly downregulated genes in the two ICC groups. Unsupervised hierarchical
      cluster analysis separated the 40 ICCs into two major branches almost completely
      according to the fluke status. The putative signature of OV-associated ICC
      exhibited elevated expression of genes involved in xenobiotic metabolism
      (UGT2B11, UGT1A10, CHST4, SULT1C1), whereas that of non-OV-associated ICC
      represented enhanced expression of genes related to growth factor signaling
      (TGFBI, PGF, IGFBP1, IGFBP3). Additional random permutation tests identified a
      total of 49 genes whose expression levels were significantly different between
      the two groups. We also identified genes associated with macroscopic type of
      ICCs. In conclusion, these data may not only contribute to clarification of
      common and OV-specific mechanisms underlying ICC, but also may serve as a
      starting point for the identification of novel diagnostic markers or therapeutic
      targets for the disease.

PMID- 17006948
TI  - Sleep-disordered breathing and insulin resistance.

PMID- 17006949
TI  - SPINFAST: using structure alignment profiles to enhance the accuracy and assess
      the reliability of protein side-chain modeling.
AB  - We present a novel, knowledge-based method for the side-chain addition step in
      protein structure modeling. The foundation of the method is a conditional
      probability equation, which specifies the probability that a side-chain will
      occupy a specific rotamer state, given a set of evidence about the rotamer states
      adopted by the side-chains at aligned positions in structurally homologous
      crystal structures. We demonstrate that our method increases the accuracy of
      homology model side-chain addition when compared with the widely employed
      practice of preserving the side-chain conformation from the homology template to
      the target at conserved residue positions. Furthermore, we demonstrate that our
      method accurately estimates the probability that the correct rotamer state has
      been selected. This interesting result implies that our method can be used to
      understand the reliability of each and every side-chain in a protein homology
      model.

PMID- 17006950
TI  - Crystal structure of the diadenosine tetraphosphate hydrolase from Shigella
      flexneri 2a.

PMID- 17006951
TI  - Impact of long work hours on police officers and the communities they serve.
AB  - BACKGROUND: Police officers in the United States often are overly fatigued
      because of long and erratic work hours, shift work, and insufficient sleep. These
      factors likely contribute to elevated levels of morbidity and mortality,
      psychological disorders, and family dysfunction observed among police. Fatigue
      related impairments to officer performance and decision making can generate
      unexpected social and economic costs. METHODS: Information was gathered from the
      literature and analysis of government data as well as meetings with sleep
      researchers, police executives, and union officials in order to understand the
      causes and consequences of police long work hours. RESULTS AND CONCLUSIONS: Long
      work hours and shift work threaten police officer health, safety, and
      performance. This situation is aggravated by understaffing associated with
      demographic shifts and new threats to homeland security. Ongoing research
      suggests that the police may be a useful model occupational group for basic and
      applied research on sleep, fatigue, and human performance.

PMID- 17006952
TI  - Health status of Army Chemical Corps Vietnam veterans who sprayed defoliant in
      Vietnam.
AB  - BACKGROUND: U.S. Army Chemical Corps veterans handled and sprayed herbicides in
      Vietnam resulting in exposure to Agent Orange and its contaminant 2,3,7, 8
      tetrachlorodibenzo-p-dioxin (TCDD or dioxin). This study examined the long-term
      health effects associated with herbicide exposure among these Vietnam veterans.
      METHODS: A health survey of these 1,499 Vietnam veterans and a group of 1,428 non
      Vietnam veterans assigned to chemical operations jobs was conducted using a
      computer-assisted telephone interview (CATI) system. Exposure to herbicides was
      assessed by analyzing serum specimens from a sample of 897 veterans for dioxin.
      Logistic regression analyses were used to estimate the risk of selected medical
      outcomes associated with herbicide exposure. RESULTS: Odds ratios for diabetes,
      heart disease, hypertension, and chronic respiratory disease were elevated, but
      not significantly (P>0.05) for those who served in Vietnam. However, they were
      significantly elevated among those Vietnam veterans who sprayed herbicides:
      diabetes, odds ratio (OR)=1.50 (95% confidence interval [95%CI]=1.15-1.95); heart
      disease, OR=1.52 (1.18-1.94); hypertension, OR=1.32 (1.08-1.61); and chronic
      respiratory condition, OR=1.62 (1.28-2.05). Hepatitis was associated with Vietnam
      service, but not with herbicide application. CONCLUSIONS: Vietnam veterans who
      were occupationally exposed to herbicide experienced a higher risk of several
      chronic medical conditions relative to other non-Vietnam veterans. A potential
      selection bias is of concern. However, there were relatively high participation
      rates in both the Vietnam and non-Vietnam veteran groups, and the prevalence
      rates of some of these medical conditions among non-Vietnam veterans were
      comparable to general populations. Therefore, self-selection factors are
      considered unlikely to have biased the study results.

PMID- 17006953
TI  - The chloromethylketone protease inhibitor AAPF(CMK) also targets ATP-dependent
      helicases and SAP-domain proteins.
AB  - We have been studying a nuclear protease, which appears to be involved in
      cellular transformation, as well as in infections with high-risk human
      papillomaviruses (HPVs). This protease has a chymotrypsin-like substrate
      specificity and the chloromethylketone inhibitor AAPF(CMK) is a potent (and
      relatively selective) inhibitor of it. Recently, we have observed that AAPF(CMK)
      has potent effects in some model systems which appear not to be mediated by
      decreases in the nuclear protease. Here we show that AAPF(CMK) selectively reacts
      with ATP-dependent helicases as well as a limited spectrum of proteins in other
      DNA repair/chromatin remodeling nuclear complexes, including for example Cohesin
      complex components and proteins containing SAP-domains. In vitro, AAPF(CMK)
      selectively reacts with SV40 large T antigen, and inhibits its helicase activity.

PMID- 17006954
TI  - X-ray fluorescence microprobe imaging in biology and medicine.
AB  - Characteristic X-ray fluorescence is a technique that can be used to establish
      elemental concentrations for a large number of different chemical elements
      simultaneously in different locations in cell and tissue samples. Exposing the
      samples to an X-ray beam is the basis of X-ray fluorescence microscopy (XFM).
      This technique provides the excellent trace element sensitivity; and, due to the
      large penetration depth of hard X-rays, an opportunity to image whole cells and
      quantify elements on a per cell basis. Moreover, because specimens prepared for
      XFM do not require sectioning, they can be investigated close to their natural,
      hydrated state with cryogenic approaches. Until several years ago, XFM was not
      widely available to bio-medical communities, and rarely offered resolution better
      then several microns. This has changed drastically with the development of third
      generation synchrotrons. Recent examples of elemental imaging of cells and
      tissues show the maturation of XFM imaging technique into an elegant and
      informative way to gain insight into cellular processes. Future developments of
      XFM-building of new XFM facilities with higher resolution, higher sensitivity or
      higher throughput will further advance studies of native elemental makeup of
      cells and provide the biological community including the budding area of
      bionanotechnology with a tool perfectly suited to monitor the distribution of
      metals including nanovectors and measure the results of interactions between the
      nanovectors and living cells and tissues.

PMID- 17006955
TI  - Matrix regulation of skeletal cell apoptosis III: mechanism of ion pair-induced
      apoptosis.
AB  - Our previous work has demonstrated that while the Ca(2+) and Pi ions acting in
      concert function as a potent osteoblast apoptogen, the underlying mechanisms by
      which it activates cell death is not known. We hypothesize that the ion pair
      causes release of Ca(2+) from intracellular stores ([Ca(2+)]i); the increase in
      intracellular calcium prompts the mitochondria to uptake more calcium. This
      accumulation of calcium eventually results in the loss of mitochondrial membrane
      potential (MMP) and, subsequently, apoptosis. To test this hypothesis, we
      evaluated apoptosome formation in MC3T3-E1 osteoblast-like cells treated with the
      ion pair. Western blot analysis indicated migration of cytochrome-c and
      Smac/DIABLO from mitochondria to the cytoplasm. Inhibition of either the electron
      transfer chain (with antimycin a and rotenone), or the activation of a MMP
      transition (with bongkrekic acid) inhibited apoptosis in a dose-dependent manner.
      Pre-treating osteoblasts with ruthenium red, a Ca(2+) uniporter inhibitor of both
      mitochondria and the endoplasmic reticulum (ER), also completely abolished
      Ca(2+.)Pi-induced apoptosis. Moreover, we showed that an increase in [Ca(2+)]i
      preceded the increase in MMP over the first 45 min of treatment; a mitochondrial
      membrane permeability transition was evident at 75 min. To determine the role of
      ER, Ca(2+) stores in the generation of the apoptotic signal by the ion pair,
      cells were treated with several inhibitors. Apoptosis was inhibited when cells
      were treated with dantrolene, an inhibitor of ER ryanodine receptors, and 2
      aminodiphenylborate, an IP3 Ca(2+) channel inhibitor, but not cyclopiazonic acid,
      an ER Ca(2)-ATPase inhibitor. Together, these data demonstrate that Ca(2+) Pi
      induced osteoblast apoptosis is characterized by the generation of an apoptosome
      and that Ca(2+) release from ER stores may promote ion pair-dependent cell death.

PMID- 17006956
TI  - A new approach for bone marrow-derived stem cells intrapancreatic
      autotransplantation in diabetic rats.
AB  - PURPOSE: A new technique for stem cells intrapancreatic autotransplantation in
      rats. BASIC PROCEDURES: Section of a femoral diaphysis and aspirations of the
      bone marrow in both femoral segments were performed. A Kirschner needle was
      placed into the femur. Cells were isolated in Ficoll gradients and preserved at 4
      6 degrees C. The second day, cells were injected, via aortic celiac trunk, into
      the pancreas of the same rat. RESULTS: Femoral surgery were well tolerated.
      Intrapancreatic homing of the injected cells was suggested with methylene blue
      injection that stained the pancreas, and proved by labeled cells in pancreas
      sections. Cell counts after Ficoll isolation were 1 x 10(6) +/- 2 x 10(5) ES.
      CONCLUSIONS: A technique is described for stem cell autotransplantation in rats.
      First we obtain autologous bone marrow-derived stem cells. Second, we inject the
      cells in the pancreas of the donor rat. This approach can be applied to
      experimental diabetes and other pancreatic processes.

PMID- 17006957
TI  - Collaboration with microsurgery prevents arterial complications and provides
      superior success in partial liver transplantation.
AB  - Hepatic artery thrombosis is the most common technical complication in liver
      transplantation. The objective of this study was to investigate the arterial
      complications of partial liver transplantation using microsurgical technique. At
      a period of 31-months, we participated in a total of 42 right lobes, 7 left
      lobes, and 1 whole-liver liver transplantations from cadaveric (n = 20) or living
      (n = 30) donors. Hepatic artery anastomosis was performed using microsurgical
      techniques. All anastomoses were accomplished successfully. Fifteen patients
      expired postoperatively and 35 hepatic artery anastomoses remained patent at a
      mean follow-up period of 10.6 +/- 8.4 months. The mean diameters of the donor and
      recipient hepatic arteries were 2.9 +/- 1.2 mm and 3.2 +/- 1.1 mm, respectively.
      Specific technical challenges were encountered during operation in eight cases
      (16%). We have found that microsurgical techniques are not only useful for a
      superior anastomosis but also reliable to adapt to vascular anomalies with less
      arterial complications. complications.

PMID- 17006958
TI  - MS-KIF18A, a kinesin, is associated with estrogen receptor.
AB  - The study of MS-KIF18A kinesin protein is focused on its cellular distribution
      and association with a cargo protein. Indirect immunofluorescence (IF) analyzed
      the intracellular distribution of endogenous MS-KIF18A and the transfected
      enhanced green fluorescence protein (eGFP)-MS-KIF18A in osteogenic cells. In both
      cases, the proteins were localized at the plasma membrane, cytosol, and nucleus.
      Bioinformatics analysis suggested interactions between MS-KIF18A and estrogen
      receptor (ERalpha) which were further elucidated by immunoprecipitation (IP). We
      identified interaction between endogenous MS-KIF18A with 66 and 46 kDa isoforms
      of ERalpha in MBA-15 cells. Moreover, MS-KIF18A and 66 kDa ERalpha complex has
      been demonstrated between ectopically expressed proteins in COS-7 cells. We have
      shown that anti-MS-KIF18A antibody immunoprecipitated the ERalpha and pERK in
      cells challenged with 17beta-estrogen (17beta-E2). The hormone activation induced
      mitogen-activated protein kinases (MAPK) pathway and increased p-ERK. The
      activation was interfered when cells were pre-treated with either ICI-182,780 or
      MAPK inhibitor PD98059 prior the challenge with 17beta-E2 that resulted in a
      decrease in association between MS-KIF18A and p-ERK1/2. The obtained results
      suggest a role for the proteins in a non-genomic response of MBA-15 cells
      challenged with 17beta-E2. This study presents a novel interaction between MS
      KIF18A and ER that may have important physiological and pharmacological
      implications for estrogen action in various cells.

PMID- 17006959
TI  - Refill adherence for patients with asthma and COPD: comparison of a pharmacy
      record database with manually collected repeat prescriptions.
AB  - PURPOSE: To compare refill adherence data based on two different methods of data
      capturing, that is, manually collected repeat prescriptions and a pharmacy record
      database. METHODS: The study comprised a comparison of adherence data from
      manually collected repeat prescriptions of asthma and chronic obstructive
      pulmonary disease (COPD) drugs with fixed dosages dispensed in 2002 and the
      corresponding data from a pharmacy record database. Data were collected in the
      county of Jamtland in Sweden. Refill adherence was calculated for the different
      collection methods. RESULTS: Data from 285 manually collected repeat
      prescriptions for asthma/COPD drugs for 2002 showed that 35% of the prescribings
      had been satisfactory refilled, while 42% showed an undersupply and 23% an
      oversupply. The pharmacy record database had 490 prescribings for asthma/COPD
      drugs registered in 2002, 28% of these had a satisfactory refill adherence, while
      43% showed an undersupply, and 29% an oversupply. Based on the database it could
      be shown that 11% of the individuals had used more than one repeat prescription
      of the same medicine during 2002. Based on the pharmacy record database for 1999
      2002, it was shown that 29% of the prescribings had been satisfactory refilled
      whereas undersupply increased (53%) and oversupply decreased (18%) as compared to
      the 1-year data. CONCLUSIONS: Refill adherence determined from manually collected
      repeat prescriptions and from a pharmacy record database did not differ for a 1
      year period. Four-year data might give a better overview of patients' refill
      adherence than 1-year data.

PMID- 17006960
TI  - Use of albumin in three French university hospitals: is prescription monitoring
      still useful in 2004?
AB  - PURPOSE: Use of albumin (indications and quantities involved) has not been
      assessed in France since major changes occurred after the publication of Cochrane
      group meta-analysis. The objectives of this study were to measure the repartition
      of albumin indications in three French university hospitals in 2004 and to assess
      the feasibility and usefulness to implement a prescription-monitoring program.
      METHODS: Exhaustive record of albumin prescription during 2 months in three
      French university hospitals of Marseille. Inclusion of all patients with a first
      prescription of albumin between 15 March 2004 and 15 May 2004. Indication,
      formulation and quantity prescribed were recorded for each prescription. RESULTS:
      One hundred and eighty-seven patients received a total of 426 prescriptions for a
      total quantity of 21 094 g of albumin during the study. The first indications
      were hypoalbuminemia (33% of total quantity), plasmapheresis (30.2%) and ascites
      or hepatorenal syndrome (13.7%). Fifty per cent of total quantity was used by 14
      patients (7.5% of included patients). CONCLUSIONS: Most of albumin consumption in
      our study is concentrated on recognized indications or indications without
      alternative to albumin. The different levels of analysis (number of patient
      treated, number of prescription and quantities used) must be taken into account
      when analyzing medications such as albumin. Only a marginal proportion of
      consumption is expected to be saved with close monitoring of indications.

PMID- 17006961
TI  - A sensitive and reliable semi-quantitative real-time PCR assay to detect JAK2
      V617F in blood.
AB  - Diagnosis of the myeloproliferative disorders, polycythemia vera (PV), essential
      thrombocythemia (ET) and idiopathic myelofibrosis (IMF) is difficult due to lack
      of diagnostic markers. Recently, the acquisition of a mutation in the Janus
      kinase 2 (JAK2) gene by hemopoietic cells has been described as a genetic defect
      underlying myeloproliferative disorders. The mutation leads to constitutive
      activation of JAK2, a tyrosine kinase involved in cytokine receptor signalling.
      Because of the clinical importance of this mutation (JAK2 V617F) in diagnosing
      myeloproliferative disorders and its relevance for disease progression, we
      developed a semi-quantitative real-time PCR test to detect JAK2 V617F. With this
      assay, quantities down to 0.8% JAK2 V617F amongst wild-type DNA could reliably be
      detected. For quantification purposes, low intra- and inter-assay variabilities
      ensure good reproducibility of the assay. Thus the JAK2 V617F qPCR assay
      described here is quick, robust, simple and more sensitive than direct
      sequencing, RFLP, ARMS assay and other methods published so far to detect JAK2
      V617F. We therefore believe that the assay will contribute to early diagnosis of
      myeloproliferative disorders and to disease management, especially when JAK2
      specific inhibitors have become available for therapeutic use.

PMID- 17006963
TI  - A comparison of patient and population values for health states in varicose veins
      patients.
AB  - Cost utility analyses typically incorporate preferences based upon the mean
      values for health states generated from a sample of the general population. The
      main argument for using general population values rests upon the premise that in
      a publicly funded health care system the main objective of the health care system
      is a societal one, namely to maximise health subject to equity concerns.
      Alternatively, it can be argued that patients themselves should be asked to value
      their own health state given that they have first hand experience of the state
      being valued. This paper investigates the relationship between patient and
      general population values within the context of a randomised controlled trial to
      compare alternative treatments for varicose veins. It was found that patients'
      own health valuations tended to be higher than those of the general population
      sample. The results from this study have important implications for economic
      evaluation. The incremental QALY gain for patients receiving treatment for
      moderate varicose veins would be almost halved if patients' own values were used
      to estimate QALYs in contrast to the general population values. The results also
      suggest that the variant of elicitation technique may be more important than the
      source of those values in revealing discrepancies.

PMID- 17006962
TI  - Biological interactions between herpesviruses and cyclooxygenase enzymes.
AB  - Decades ago, medical researchers noted that non-steroidal anti-inflammatory drugs
      (NSAIDs), for example aspirin and indomethacin, modulate primary herpesvirus
      infections and diminish reactivation of latent herpesvirus infections. NSAIDs
      inhibit cyclooxygenase (COX) enzymes, molecules necessary for generation of
      prostaglandins. Numerous studies indicate that herpesvirus infections elicit
      elevated levels of cyclooxygenase 2 (COX-2) with a resultant increase in
      prostaglandin E(2) levels (PGE(2)). Thus, the biochemical pathway underlying the
      anti-herpetic mechanism of NSAIDs is linked to the inhibition of COX. The precise
      roles of COX-2 and PGE(2) in the viral life cycle are unknown. However, among the
      alphaherpesvirus, betaherpesvirus and gammaherpesvirus subfamilies,
      evolutionarily conserved mechanisms ensure modulated expression of COX molecules,
      underscoring their importance in viral replication and virus-host interactions.

PMID- 17006964
TI  - Kinetic distribution of paeoniflorin in cortex of normal and cerebral ischemia
      reperfusion rats after intravenous administration of Paeoniae Radix extract.
AB  - The time course of paeoniflorin in the cortex of normal and cerebral ischemia
      reperfusion rats, following intravenous administration of Paeoniae Radix extract
      at a dose of 60 mg/kg of paeoniflorin, was determined using high-performance
      liquid chromatographic (HPLC) assay. The results showed that paeoniflorin could
      penetrate through the blood-brain barrier to reach the cortex, and that the
      injuries of ischemia-reperfusion could play an important role in pharmacokinetic
      process of paeoniflorin in the cortex after intravenous administration of
      Paeoniae Radix extract. The cortex concentrations of paeoniflorin in cerebral
      ischemia-reperfusion rats were lower 5 min after dosing and declined more slowly
      than that in normal control.

PMID- 17006965
TI  - Validation of a simple HPLC method for DRF-4848, a novel COX-2 inhibitor suitable
      for pharmacokinetic application in rats.
AB  - For pharmacokinetic and toxicokinetic purpose a simple HPLC-UV method has been
      developed and validated for the estimation of DRF-4848, a novel COX-2 inhibitor
      in rat plasma. A liquid-liquid extraction was used to extract DRF-4848 and
      internal standard (IS, DRF-4367) from rat plasma. The analysis was performed on a
      C(18) column with UV detection at 285 nm. The isocratic mobile phase, 0.01 M
      potassium dihydrogen ortho phosphate (pH 3.2) and acetonitrile (50:50, v/v) was
      run at a flow rate of 1 mL/min. The retention times of DRF-4848 and IS were 6.8
      and 11.2 min, respectively. Absolute recovery for analyte and IS was >80% from
      rat plasma. A linear response was observed over a concentration range 0.1-20
      microg/mL. The lower limit of quantification (LLOQ) of DRF-4848 was 0.1
      microg/mL. The inter- and intra-day precisions in the measurement of quality
      control (QC) samples, 0.1, 0.3, 8.0 and 15.0 microg/mL, were in the range 1.74
      8.70% relative standard deviation (RSD) and 0.75-8.43% RSD, respectively.
      Accuracy in the measurement of QC samples was in the range 93.29-116.51% of the
      nominal values. Analyte and IS were stable in the battery of stability studies
      viz., benchtop, autosampler, long-term and freeze/thaw cycles.

PMID- 17006966
TI  - High-performance liquid chromatographic method for the determination of
      mangiferin in rat plasma and urine.
AB  - A reversed-phase high-performance liquid chromatography assay for mangiferin in
      rat plasma and urine was developed. Rutin was employed as an internal standard.
      The mobile phase consisted of acetonitrile-water (16:84, v/v) containing 3%
      acetic acid at a flow rate of 1 mL/min. Detection was at 257 and 365 nm for
      mangiferin in plasma and urine, respectively. The limit of quantitation (LOQ) of
      mangiferin was 0.6 microg/mL in plasma, and 0.48 microg/mL in urine. The standard
      curve was linear from 0.6 to 24 microg/mL in plasma, and 0.48 to 24 microg/mL in
      urine, both intra- and inter-day precision of the mangiferin were determined and
      their RSD did not exceed 10%. The method provides a technique for rapid analysis
      of mangiferin in rat plasma and urine, which can be used in pharmacokinetic
      studies.

PMID- 17006967
TI  - Usage of the claim database of national health insurance programme for analysis
      of cisapride-erythromycin co-medication in Taiwan.
AB  - PURPOSE: This study aimed to use the National Health Insurance Research Database,
      Taiwan for risk analysis of concomitant use of cisapride and erythromycin.
      METHODS: The sample consisted of subjects identified in the Outpatient Sampling
      Database (OSD) and Longitudinal Health Insurance Database 2000 (LHID 2000),
      derived from the original claim data of the National Health Insurance Research
      Database, Taiwan. RESULTS: According to the LHID 2000, a total of 464 individuals
      experienced 685 episodes of cisapride-erythromycin co-medication prescribed by
      295 physicians, revealing a prevalence of 4.5% concomitant use, with higher
      prevalence in clinics (9.2%) than in other medical institutes (3.7-5.4%). Among
      the co-medication episodes, 81.9% and 61.2% were prescribed from the same health
      institutes and by the same physicians, respectively. No medical record of cardiac
      arrhythmias was found among these patients in 2001 and 2002, probably due to the
      fact that 78.9% of the 464 individuals were under age 16, 84.0% had short
      exposure duration (1-4 days) and 98.0% of the episodes were prescribed with a
      cisapride dose of less than 0.8 mg/kg/day. CONCLUSIONS: Findings from this study
      suggest that there exists an urgent need for accreditation in terms of
      pharmacovigilance of clinical sites and their practicing physicians for the
      prevention of irrational concomitant prescription in Taiwan. Our findings also
      indicate that it is necessary to investigate other possible conditions of
      potentially dangerous co-medication in Taiwan and other developing countries.

PMID- 17006968
TI  - Japanese cancer patients' communication style preferences when receiving bad
      news.
AB  - This study describes the communication style preferences of Japanese patients
      when receiving bad news, examines the factor structure of the measure for
      patients' preferences (MPP) in a Japanese population, and explores variables that
      may be associated with patients' communication style preferences. Five hundred
      twenty-nine cancer outpatients completed several psychosocial measures including
      the Japanese version of the MPP (MPP-J), the Mental Adjustment to Cancer Scale
      (MAC), and the Hospital Anxiety and Depression Scale (HADS). The patients desired
      detailed information and a supportive environment when receiving bad news. The
      MPP-J demonstrated a 5-factor structure: support, facilitation, medical
      information, clear explanation, and encouraging question-asking. Regression
      analyses indicated that a female gender, the fighting spirit and anxious
      preoccupation dimensions of the MAC were positively associated with all 5 MPP-J
      factors. In conclusion, Japanese cancer patients' preferences for communication
      when receiving bad news differ somewhat from those of American patients. Japanese
      physicians should encourage patients to ask questions and should consider the
      demographic (e.g. gender), medical (disease status) and psychosocial
      characteristics (fighting spirit and anxious preoccupation) of patients when
      delivering bad news.

PMID- 17006969
TI  - Pegylated liposomal doxorubicin, melphalan and prednisone therapy for elderly
      patients with multiple myeloma.
AB  - Melphalan & Prednisone (MP) is considered as the standard therapy for Multiple
      Myeloma (MM) patients not eligible for high-dose therapy. Here, we report the
      results of a phase I-II study to evaluate the feasibility and efficacy of the
      association of PLD to the conventional MP regimen during the first six cycles of
      the front-line therapy for untreated MM patients older than 70. Thirty patients
      were included in the study with a median age of 77 years (71-84) and a M/F ratio
      of 17/13. The phase I of the study demonstrated that the maximum tolerable dose
      of PLD in this setting was 30 mg/m(2), so it was the final dose evaluated in the
      study. Twenty-nine patients were valuable for response, which was: complete in 4
      (14%) partial in 15 (52%) minor/no changes in 7 (24%) and progressive in 3 (10%).
      The median progression free survival (PFS) was 24 months. The median overall
      survival (OS) has not been reached yet, with a 3-year probability for OS and PFS
      of 52 and 37%, respectively. Haematological toxicity was frequent but usually
      weak/moderate (grades 1 & 2 of the WHO scale) and it was resolved only with dose
      delays. Infection was a relatively frequent event (30% of patients), but only in
      4 cases it was of grade 3. No cases of palmar-plantar erythrodysesthesia were
      observed. In conclusion, pegylated liposomal doxorubicin can be safely added to
      the other chemotherapeutic drugs in the treatment of elderly MM patients, which
      can be very useful for patients in whom novel agents are not tolerated or
      inefficient.

PMID- 17006970
TI  - Discounting in economic evaluations: stepping forward towards optimal decision
      rules.
AB  - The National Institute for Clinical Excellence has recently changed its
      guidelines on discounting costs and effects in economic evaluations. In common
      with most other regulatory bodies it now requires that health effects should be
      discounted at the same rate as costs. We show that the guideline leads to sub
      optimal decisions because it fails to account for the changing value of health.
      NICE (and other regulatory bodies) should either use differential discounting or
      stipulate how the changing value of health should otherwise be dealt with. We
      also show how binding health service budget constraints should be incorporated in
      evaluations.

PMID- 17006971
TI  - Antidermatophyte activity of medicago extracts and contained saponins and their
      structure-activity relationships.
AB  - Saponin-rich extracts of Medicago sativa L. have been shown to display antifungal
      activity against a range of common fungibut only a few individual saponins have
      been tested against dermatophytes. Total saponins were separately obtained from
      roots and aerial parts of Medicago sativa, M. murex, M. arabica and M. hybrida.
      Nineteen saponins and three parent triterpenoids, were tested against three
      dermatophytic fungi Microsporum gypseum, Trichophyton interdigitale and T.
      tonsurans using mircowell plate serial dilution assay to determine the Minimum
      Inhibitory Concentration (MIC). Miconazole was used as a positive control. T.
      tonsurans appeared to be the most sensitive of the dermatophytes to the active
      compounds. Aglycones showed less antifungal effect than the glycosides, which
      displayed a range of activities. Monodesmosidic glycosides of medicagenic acid
      were the most active compounds, especially the 3-O-beta-D-glucopyranoside, which
      displayed MIC less than 0.09mm against all three fungi, although those of
      hederagenin and zanhic acid also showed weak activity (MIC 3.3mm against two
      fungal species). Bidesmosidic saponins had weaker activity than monodesmosidic
      ones. This corresponds to activity of these and similar compounds against other
      fungal species but this is the first comprehensive report of activity of Medicago
      saponins against dermatophytes.

PMID- 17006972
TI  - Hypolipidemic effect of lactobacillus ferment as a functional food supplement.
AB  - The Lactobacillus ferment used in this study was composed of Lactobacillus
      fermented wheat, barley and kefir grains. Fermentation increased the CFU of
      lactic acid bacteria with a reduction in pH value and in the contents of dietary
      fi ber and glucan. Male SD rats were fed a high fat diet with or without 10%
      Lactobacillus ferment for 4 weeks. In the Lactic-F group (group fed high-fat diet
      with Lactobacillus ferment) there was a significantly reduced increase of body
      weight compared with the HF-control (group fed high-fat diet without
      Lactobacillus ferment). The food efficiency ratio (FER) tended to be decreased in
      the Lactic-F group, but there was no significant difference between the Lactic-F
      and HF-control groups. The perirenal and the epididymal fat weights in the normal
      dietary group (control) and in the Lactic-F group were significantly lower than
      those of the HF-control. The serum HDL-cholesterol and the total cholesterol in
      the Lactic-F group were similar to the control group, and were significantly
      different from those of the HF-control. These results indicated that the
      Lactobacillus ferment is a functional material having antiobesity effects, with
      use as a supplement in functional, health-favoring food.

PMID- 17006973
TI  - Bioassay-guided isolation of antiatherosclerotic phytochemicals from Artocarpus
      altilis.
AB  - The cytoprotective effects of various solvent extracts of Artocarpus altilis
      (Parkinson) Fosberg were evaluated. The cytoprotective effects were determined in
      human U937 cells incubated with oxidized LDL (OxLDL) using the 4-[3-(4
      iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1, 3-benzene disulfonate (WST-1)
      assay. The results demonstrated that the ethyl acetate extract showed
      cytoprotective activities. To identify the main cytoprotective components, a
      bioassay guided isolation of the ethyl acetate extract afforded b-sitosterol (1)
      and six flavonoids (2-7). Their chemical structures were established on the basis
      of spectroscopic evidence and comparison with literature data. Of these
      compounds, compound 6 was obtained from A. altilis for the first time. The
      cytoprotective effect offers good prospects for the medicinal applications of A.
      altilis.

PMID- 17006974
TI  - Flavonoids as antagonists at A1 adenosine receptors.
AB  - This study aimed to investigate the potential for flavonoid action at A(1)
      adenosine receptors in vitro. In a radioligand binding assay for A(1) adenosine
      receptor occupancy in particulate preparations from guinea-pig cerebral cortex,
      flavonoids competed in concentration-dependent manners with Hill slopes typically
      not different from unity. Of the flavonoids tested, quercetin showed highest
      affinity (pKi value of 5.33). At a concentration of 28 mm, quercetin evoked a
      rightward shift in the N(6)-cyclopentyladenosine-induced inhibition of
      electrically evoked contractions of the guinea-pig isolated ileum, allowing the
      calculation of a pK(i) value of 4.71. These data suggest, therefore, that
      flavonoids represent an additional dietary source of A(1) adenosine receptor
      antagonists (beyond the methylxanthines, caffeine and theophylline).

PMID- 17006975
TI  - Effect of the water extract and ethanol extract from traditional Chinese
      medicines Angelica sinensis (Oliv.) Diels, Ligusticum chuanxiong Hort. and Rheum
      palmatum L. on rat liver cytochrome P450 activity.
AB  - Angelica sinensis (Oliv.) Diels (DG), Ligusticum chuanxiong Hort. (CX) and Rheum
      palmatum L. (DH), three well known traditional Chinese medicines (TCM), have been
      used widely for the treatment of various types of disorders in China. Herb-drug
      interactions, especially cytochrome P450 (CYP)-mediated interactions, cause an
      enhancement or attenuation in the efficacy of co-administered drugs. In this
      study, to assess the possible interactions between TCM and drugs, the effect of
      water and ethanol extracts of DG, CX and DH on cytochrome P450 were studied in
      rats. The activities of various CYP enzymes were determined by HPLC method.
      Treatment of rats with water extracts or ethanol extracts of DG, CX and DH at
      daily dosages equivalent to 3 g (dry herbal material)/kg all increased the
      microsome protein contents and decreased the total CYP levels. The water extract
      of DG strongly increased the activities of CYP2D6 and 3A and the water extract of
      DH significantly increased the activity of 2D6. The other water extracts all
      showed inhibition against CYP isoforms. Only the ethanol extract of DG and DH
      increased the CYP2D6 and 3A activities, respectively, and the other ethanol
      extracts all decreased the level of CYP isoforms. All extract treatments had
      significant effects on CYP isoforms activities, whether induction or inhibition,
      compared with the blank control. Thus, caution should be paid to possible drug
      interactions of DG, CX, DH and CYP substrates.

PMID- 17006976
TI  - Hypolipidaemic activity of aqueous Ocimum basilicum extract in acute
      hyperlipidaemia induced by triton WR-1339 in rats and its antioxidant property.
AB  - Hyperlipidaemia, atherosclerosis and related diseases are becoming a major health
      problem in developing countries. Ocimum basilicum is one of the medicinal plants
      widely used in Morocco to reduce plasma cholesterol and to reduce the risk of
      atherosclerosis-related diseases. However, mechanisms underlying the reported
      hypolipidaemic effect of this plant have not been investigated. This study
      evaluates the lipid lowering effect of aqueous Ocimum basilicum extract in Triton
      WR-1339-induced hyperlipidaemic rats. Hyperlipidaemia was developed in animals by
      intraperitoneal injection of Triton (200 mg/kg). After injection of Triton the
      animals were divided into three treatment groups: hyperlipidaemic,
      hyperlipidaemic plus herb extract and hyperlipidaemic plus fenofibrate treated
      rats. At 7 h after the Triton injection, levels of plasma cholesterol,
      triglycerides and LDL-cholesterol in rats treated also with the Ocimum basilicum
      extract (0.5 g/100 g body weight) were, respectively, 50%, 83% and 79% lower than
      Triton-treated rats and HDL-cholesterol was 129% higher than in rats given Triton
      alone. At 24 h following Ocimum basilicum administration, total cholesterol,
      triglycerides and LDL-cholesterol levels decreased by 56%, 63% and 68%,
      respectively, in comparison with the Triton treated group and HDL-cholesterol was
      not increased significantly. The hypolipidaemic effect exerted by Ocimum
      basilicum extract was markedly stronger than the effect induced by fenofibrate
      treatments. Further it was demonstrated that Ocimum basilicum aqueous extract
      displayed a very high antioxidant power. These results indicate that Ocimum
      basilicum extract may contain hypolipidaemic and antioxidant substances and its
      use as a therapeutic tool in hyperlipidaemic subjects may be of benefit and
      encourage further investigation in this field.

PMID- 17006977
TI  - Randomized clinical trial of postoperative hernia prophylaxis in open bariatric
      surgery.
AB  - BACKGROUND: Postoperative hernia following bariatric procedures is more common
      than in other groups of surgical patients, and remains a serious problem. Gastric
      bypass is the most often performed bariatric procedure and, despite the
      increasing popularity of a laparoscopic approach, many morbidly obese patients
      are still offered open procedures. The aim of this study was to assess the
      effects of prophylactic polypropylene mesh in morbidly obese patients undergoing
      gastric by-pass surgery. METHODS: The study randomized 74 patients undergoing
      open Roux-en-Y gastric bypass into two groups: wound closure with (n = 36) or
      without (n = 38) a polypropylene mesh. Mean(s.d.) body mass and body mass index
      in the mesh group were 137.3(24.5) kg and 46.2(7.1) kg/m(2) and in the non-mesh
      group were 139.0(24.9) kg and 46.8(7.6) kg/m(2) respectively. In the non-mesh
      group, the wound was closed with a polypropylene suture. Patients in the mesh
      group had in addition a polypropylene mesh inserted in a sublay manner. RESULTS:
      Patients were followed up for at least 6 (range 6-38) months. Hernia developed in
      eight patients in the non-mesh group but in none in the mesh group. The duration
      of hospital stay was similar in both groups: mean(s.d.) 8.4(3.2) and 10.3(5.9)
      days (P = 0.092). There were no serious complications in either group.
      CONCLUSION: The use of a mesh prevented hernia development and did not lengthen
      hospital stay.

PMID- 17006979
TI  - Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct
      clinico-pathological and epidemiological features.
AB  - Gastrinomas are defined as gastrin secreting tumors that are associated with
      Zollinger-Ellison syndrome (ZES). ZES is characterized by elevated fasting
      gastrin serum levels, positive secretin stimulation test and clinical symptoms
      such as recurrent peptic ulcer disease, gastroesophageal reflux disease and
      occasional diarrhea. Genetically, nonhereditary (sporadic) gastrinomas are
      distinguished from hereditary gastrinomas, which are associated with multiple
      endocrine neoplasia type 1 (MEN1) syndrome. In general, duodenal gastrinomas are
      small and solitary if they are sporadic and multiple as well as hereditary. The
      sporadic gastrinomas occur in the duodenum or in the pancreas while the
      hereditary gastrinomas almost all occur in the duodenum. Our series of 77
      sporadic duodenal neuroendocrine tumors (NETs) includes 18 patients (23.4%) with
      gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET
      archives of the departments of pathology in Zurich, Switzerland, and Kiel,
      Germany, 24 patients (4.5%) suffered from sporadic pancreatic gastrinomas and
      ZES. These NETs have to be distinguished from tumors with immunohistochemical
      positivity for gastrin but without evidence of ZES. An additional 19 patients
      suffered from MEN1 and ZES. These patients showed exclusively duodenal
      gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1
      associated duodenal gastrinomas is better than that of pancreatic gastrinomas,
      since they progress slowly to liver metastasis. In summary, sporadic and MEN1
      associated gastrinomas in the duodenum and pancreas show different clinico
      pathological and genetic features. The incidence of sporadic duodenal gastrin
      producing tumors is increasing, possibly due to optimized diagnostic procedures.
      In contrast, pancreatic MEN1-associated gastrinomas seem to be extremely rare. A
      considerable subset of tumors with immunohistochemical expression of gastrin but
      without evidence of ZES should be designated as functionally inactive NETs
      expressing gastrin, but not as gastrinomas.

PMID- 17006978
TI  - Human hepatic sinusoidal endothelial cells can be distinguished by expression of
      phenotypic markers related to their specialised functions in vivo.
AB  - The hepatic sinusoids are lined by a unique population of hepatic sinusoidal
      endothelial cells (HSEC), which is one of the first hepatic cell populations to
      come into contact with blood components. However, HSEC are not simply barrier
      cells that restrict the access of blood-borne compounds to the parenchyma. They
      are functionally specialised endothelial cells that have complex roles, including
      not only receptor-mediated clearance of endotoxin, bacteria and other compounds,
      but also the regulation of inflammation, leukocyte recruitment and host immune
      responses to pathogens. Thus understanding the differentiation and function of
      HSEC is critical for the elucidation of liver biology and pathophysiology. This
      article reviews methods for isolating and studying human hepatic endothelial cell
      populations using in vitro models. We also discuss the expression and functions
      of phenotypic markers, such as the presence of fenestrations and expression of
      VAP-1, Stabilin-1, L-SIGN, which can be used to identify sinusoidal endothelium
      and to permit discrimination from vascular and lymphatic endothelial cells.

PMID- 17006980
TI  - Do probiotics have a therapeutic role in gastroenterology?
AB  - Several hundred species of bacteria inhabit the gut, and affect its cell biology,
      morphology and homeostasis. Many bacteria are however potential pathogens,
      especially if the integrity of the epithelial barrier is physically or
      functionally breached. Conversely, the interaction between host and commensal
      microbes can confer important health benefits. This has led to commercial and
      public interest in "probiotics", live microbes principally taken as food
      supplements. Might probiotics also be used in disease therapy? Experimental
      evidence that probiotics modulate gut physiology, particularly barrier integrity
      and immunological function, underpins exciting new gastroenterological research.
      We discuss below the scientific basis for probiotic effects and present a
      critical perspective for their use in relation to gastrointestinal disease.

PMID- 17006981
TI  - H pylori and gastric cancer: shifting the global burden.
AB  - Infection with H pylori leads to a persistent chronic inflammation of the gastric
      mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous
      studies have determined a clear correlation between H pylori infection and the
      risk of gastric cancer; however, general eradication is not recommended as cancer
      prophylaxis and time points for treatment remain controversial in different areas
      of the world. Prevalence rates in Western countries are decreasing, especially in
      younger people (< 10%); and a decline in distal gastric adenocarcinoma has been
      observed. Risk groups in Western countries still show considerably higher risk of
      developing cancer, especially in patients infected with cagA+ strains and in
      persons harboring genetic polymorphism of the IL-1B promoter (-511T/T) and the
      corresponding IL-1 receptor antagonist (IL-1RN*2). Thus, general eradication of
      all infected persons in Western countries not recommended and is limited to risk
      groups in order to achieve a risk reduction. In contrast, infection rates and
      cancer prevalence are still high in East Asian countries. A prevention strategy
      to treat infected persons may avoid the development of gastric cancer to a large
      extent and with enormous clinical importance. However, studies in China and Japan
      indicate that prevention of gastric cancer is effective only in those patients
      that do not display severe histological changes such as atrophy and intestinal
      metaplasia. Thus, prophylactic strategies to prevent gastric cancer in high risk
      populations such as China should therefore especially aim at individuals now at
      younger age when the histological alterations caused by the bacterial infection
      was still reversible. In countries with a low prevalence of gastric cancer, risk
      groups carrying cagA+ strains and IL-1 genetic polymorphisms should be identified
      and treated.

PMID- 17006983
TI  - -765G > C COX-2 polymorphism may be a susceptibility marker for gastric
      adenocarcinoma in patients with atrophy or intestinal metaplasia.
AB  - AIM: To investigate the relationship between the -765G > C COX-2 polymorphism and
      the development of different gastric lesions: atrophy or intestinal metaplasia
      and gastric adenocarcinoma. METHODS: A cross-sectional study was performed
      involving 320 Portuguese individuals (210 without evidence of neoplastic disease,
      73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal
      metaplasia) using a PCR-RFLP method. RESULTS: -765C allele was overrepresented in
      the patients with gastric adenocarcinoma (51%) when compared either with the
      control group (38%) or patients with atrophy or intestinal metaplasia (27%).
      Callele was found to be very common in our population (0.22), and a multivariate
      logistic regression analysis revealed nearly 3-fold increased risk for the
      progression to gastric adenocarcinoma in patients with atrophy or intestinal
      metaplasia carrying the -765C allele (OR = 2.67, 95% CI = 1.03-6.93; P = 0.04).
      CONCLUSION: -765C carrier status should be considered as another susceptibility
      marker for gastric adenocarcinoma development in patients with atrophy or
      intestinal metaplasia.

PMID- 17006982
TI  - H pylori status and angiogenesis factors in human gastric carcinoma.
AB  - AIM: To investigate H pylori expression in gastric cancer patients in relation to
      primary tumor angiogenic markers, such as microvessel density (MVD), thymidine
      phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53
      and circulating VEGF levels. METHODS: Angiogenic markers were analyzed
      immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA)
      and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR
      assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels
      were detected in 39 and 38 patients by ELISA, respectively. RESULTS: A total of
      69% of patients were positive for circulating IgG antibodies against H pylori.
      cagA-positive H pylori strains were found in 41% of gastric patients. vacA was
      found in 50% of patients; s1 strains were more highly expressed among vacA
      positive patients. The presence of the s1 strain was significantly associated
      with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF
      expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041).
      Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression.
      However, H pylori was not related to any angiogenic markers except for the plasma
      VEGF level (P = 0.026). CONCLUSION: H pylori antigen is related to higher plasma
      VEGF levels, but not to angiogenic characteristics. It can be hypothesized that
      the toxic effects of H pylori on angiogenesis occurs in early preclinical disease
      phase or in long-lasting aggressive infections, but only when high H pylori IgG
      levels are persistent.

PMID- 17006984
TI  - H pylori infection among 1000 southern Iranian dyspeptic patients.
AB  - AIM: To describe the frequency of H pylori infection among 1000 southern Iranian
      dyspeptic patients. METHODS: A prospective study was performed in a referral
      hospital in south of Iran from 1999 to 2005. One thousand dyspeptic patients (518
      males, mean +/- SD age of 49.12 +/- 12.82 years) consecutively underwent upper
      gastrointestinal endoscopy. Multiple gastric antral biopsy samples were taken
      from all patients for rapid urease test and histopathologic examination (96.9%
      satisfactory samples). Patients were considered H pylori-infected if one or both
      tests were positive. RESULTS: Six hundred and seventy-one patients (67.1%, 95%
      confidence interval [CI]: 64.2%-70.0%) were H pylori-infected. H pylori
      positivity was significantly more frequent in patients with peptic ulcer disease
      (PUD) than in those with non-ulcer dyspepsia (P < 0.001). Male-to-female ratio
      for duodenal and gastric ulcers was 2.7:1 and 1.5:1, respectively. Moreover, the
      duodenal-to-gastric ulcer ratio was 1.95:1. The frequency of H pylori infection
      among those with endoscopic diagnosis of gastritis, duodenal ulcer, gastric
      ulcer, and normal mucosa was 70.1% (398/568), 86.2% (150/174), 71.9% (64/89), and
      33.5% (54/161), respectively. H pylori infection, male sex, and older age were
      independently associated with PUD in multivariate analysis. H pylori positivity
      was associated with chronic gastritis, and chronic active gastritis with odds
      ratios of 34.21 (95% CI: 12.19%-96.03%) and 81.21 (95% CI: 28.85%-228.55%),
      respectively. CONCLUSION: H pylori and PUD are highly frequent in dyspeptic
      patients from south of Iran. H pylori is a cardinal risk factor for chronic
      active or inactive gastritis.

PMID- 17006985
TI  - Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in
      fibroblasts and its effect on matrix metalloproteinase secretion.
AB  - AIM: To examine the existence of Nitric oxide/cGMP sensitive store-operated
      Ca(2+) entry in mouse fibroblast NIH/3T3 cells and its influence on matrix
      metalloproteinase (MMP) production and adhesion ability of fibroblasts. METHODS:
      NIH/3T3 cells were cultured. Confocal laser scanning microscopy was used to
      examine the existence of thapsigargin-induced store-operated Ca(2+) entry in
      fibroblasts. Gelatin zymography and semiquantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) were employed to detect the involvement of
      [Ca(2+)]i and NO/cGMP in MMP secretion. The involvement of NO/cGMP-sensitive
      Ca(2+) entry in adhesion was determined using matrigel-coated culture plates.
      RESULTS: 8-bromo-cGMP inhibited the thapsigargin-induced Ca(2+) entry in 3T3
      cells. The cGMP-induced inhibition was abolished by an inhibitor of protein
      kinase G, KT5823 (1 micromol/L). A similar effect on the Ca(2+) entry was
      observed in 3T3 cells in response to a NO donor, (+/-)-S-nitroso-N
      acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin
      induced Ca(2+) entry was also observed, indicating NO/cGMP-regulated Ca(2+) entry
      in 3T3 cells. Results of gelatin zymography assay showed that addition of
      extracellular Ca(2+) concentration induced MMP release and activation in a dose
      dependent manner. RT-PCR also showed that cGMP and SNAP reduced the production of
      MMP mRNA in 3T3 cells. Experiments investigating adhesion potentials demonstrated
      that cGMP and SNAP could upgrade 3T3 cell attachment rate to the matrigel-coated
      culture plates. CONCLUSION: NO/cGMP sensitive store-operated Ca(2+) entry occurs
      in fibroblasts, and attenuates their adhesion potentials through its influence on
      MMP secretion.

PMID- 17006986
TI  - Adiponectin and its receptors in rodent models of fatty liver disease and liver
      cirrhosis.
AB  - AIM: To determine circulating and hepatic adiponectin in rodents with fatty liver
      disease or liver cirrhosis and investigate expression of the adiponectin
      receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level.
      METHODS: Fat fed rats were used as a model for fatty liver disease and bile duct
      ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and
      AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by
      immunoblot. Adiponectin was measured by ELISA. RESULTS: Systemic adiponectin is
      reduced in fat-fed rats but is elevated in mice after bile duct ligation (BDL).
      Hepatic adiponectin protein is lower in steatotic liver but not in the liver of
      BDL-mice when compared to controls. Adiponectin mRNA was not detected in human
      liver samples or primary human hepatocytes nor in rat liver but recombinant
      adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and
      AdipoR1 protein levels are similar in the liver tissue of control and fat fed
      animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and
      protein is suppressed in the liver of BDL-mice. CONCLUSION: Our studies show
      reduced circulating adiponectin in a rat model of fatty liver disease whereas
      circulating adiponectin is elevated in a mouse model of cirrhosis and similar
      findings have been described in humans. Diminished hepatic expression of
      adiponectin receptors was only found in liver cirrhosis.

PMID- 17006987
TI  - C-reactive protein is a prognostic indicator in patients with perihilar
      cholangiocarcinoma.
AB  - AIM: To evaluate prognostic indicators for the outcome of patients with perihilar
      extrahepatic cholangiocarcinoma in an unselected cohort. METHODS: We
      retrospectively analyzed 98 patients with perihilar cholangiocarcinoma. Twenty
      three patients (23.5%) underwent tumor resection. Patients with non-resectable
      tumors underwent either transpapillary or percutaneous transhepatic biliary
      drainage. Additionally, 32 patients (32.7%) received photodynamic therapy (PDT)
      and 18 patients (18.4%) systemic chemotherapy. Predefined variables at the time
      of diagnosis and characteristics considering the mode of treatment were entered
      into a Cox's proportional hazards model. Included in the analysis were age, tumor
      stage following the modified Bismuth-Corlette classification, bilirubin,
      prothrombin time (PT), C-reactive protein (CRP), carbohydrate antigen 19-9 (CA19
      9), history of weight loss, surgical resection, chemotherapy and PDT. RESULTS:
      The Kaplan-Meier estimate of overall median survival was 10.5 (95%CI: 8.4-12.6)
      mo. In the univariate analysis, low Bismuth stage, low CRP and surgical resection
      correlated significantly with better survival. In the multivariate analysis, only
      CRP (P = 0.005) and surgical resection (P = 0.029) were found to be independently
      predictive of survival in the cohort. Receiver operating characteristic (ROC)
      analysis identified a CRP level of 11.75 mg/L as the value associated with the
      highest sensitivity and specificity predicting a survival > 5 mo. Applying Kaplan
      Meier analysis, patients with a CRP < 12 mg/L at the time of diagnosis had a
      significantly longer median survival than patients with higher values (16.2 vs
      7.6 mo; P = 0.009). CONCLUSION: This retrospective analysis identified CRP level
      at the time of diagnosis as a novel indicator for the prognosis of patients with
      perihilar cholangiocarcinoma. It should be evaluated in future prospective trials
      on this entity.

PMID- 17006988
TI  - Intensity-modulated radiation therapy with concurrent chemotherapy for locally
      advanced cervical and upper thoracic esophageal cancer.
AB  - AIM: To evaluate the dosimetry, efficacy and toxicity of intensity-modulated
      radiation therapy (IMRT) and concurrent chemotherapy for patients with locally
      advanced cervical and upper thoracic esophageal cancer. METHODS: A retrospective
      study was performed on 7 patients who were definitively treated with IMRT and
      concurrent chemotherapy. Patients who did not receive IMRT radiation and
      concurrent chemotherapy were not included in this analysis. IMRT plans were
      evaluated to assess the tumor coverage and normal tissue avoidance. Treatment
      response was evaluated and toxicities were assessed. RESULTS: Five- to nine-beam
      IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the
      primary tumor with 6-MV photons. The minimum dose received by the planning tumor
      volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription
      dose (standard deviation [SD]: 3.7%-5.7%). The minimum dose received by the PTV
      of the clinical tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%) of the prescribed
      dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients
      achieved complete response. Of them, 2 developed local recurrences and 2 had
      distant metastases, 3 survived with no evidence of disease. After treatment, 2
      patients developed esophageal stricture requiring frequent dilation and 1 patient
      developed tracheal-esophageal fistula. CONCLUSION: Concurrent IMRT and
      chemotherapy resulted in an excellent early response in patients with locally
      advanced cervical and upper thoracic esophageal cancer. However, local and
      distant recurrence and toxicity remain to be a problem. Innovative approaches are
      needed to improve the outcome.

PMID- 17006989
TI  - Prevalence of H pylori associated "high risk gastritis" for development of
      gastric cancer in patients with normal endoscopic findings.
AB  - AIM: To investigate the prevalence of H pylori associated corpus-predominant
      gastritis (CPG) or pangastritis, severe atrophy, and intestinal metaplasia (IM)
      in patients without any significant abnormal findings during upper-GI endoscopy.
      METHODS: Gastric biopsies from 3548 patients were obtained during upper GI
      endoscopy in a 4-year period. Two biopsies from antrum and corpus were
      histologically assessed according to the updated Sydney-System. Eight hundred and
      forty-five patients (mean age 54.8 +/- 2.8 years) with H pylori infection and no
      peptic ulcer or abnormal gross findings in the stomach were identified and
      analyzed according to gastritis phenotypes using different scoring systems.
      RESULTS: The prevalence of severe H pylori associated changes like pangastritis,
      CPG, IM, and severe atrophy increased with age, reaching a level of 20% in
      patients of the age group over 45 years. No differences in frequencies between
      genders were observed. The prevalence of IM had the highest increase, being 4
      fold higher at the age of 65 years versus in individuals less than 45 years.
      CONCLUSION: The prevalence of gastritis featuring at risk for cancer development
      increases with age. These findings reinforce the necessity for the histological
      assessment, even in subjects with normal endoscopic appearance. The age-dependent
      increase in prevalence of severe histopathological changes in gastric mucosa,
      however, does not allow estimating the individual risk for gastric cancer
      development--only a proper follow-up can provide this information.

PMID- 17006990
TI  - Genetic association of autoimmune hepatitis and human leucocyte antigen in German
      patients.
AB  - AIM: To report on our large German collective and updated data of 142 patients
      with autoimmune hepatitis (AIH) type 1. METHODS: Key investigations performed
      were liver biopsy, serum autoantibodies as well as serum markers such as IgG and
      elevated transaminases. Antinuclear antigen (ANA) and smooth muscle antigen (SMA)
      autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by
      the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP)
      autoantibodies either with or without ANA or SMA autoantibodies. RESULTS: Most
      prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90
      patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42
      patients, 30%). Compared to the Italian and North American patients, we found
      fewer patients with a DQ2 subtype. Furthermore, the B8-DR3-DQ2 human leucocyte
      antigen (HLA) was also less prominent compared to the North American patients.
      However, prevalences of B8, DR3, DR4, DR7, DR11 and DR13 were comparable to the
      Italian and North American patients. Furthermore, we report on an additional
      subgroup of patients with SLA/LP positive AIH. Generally, in this subgroup of
      patients the same HLA subtypes were favoured as the AIH type 1. CONCLUSION:
      Although HLA subtypes were comparable between these three collectives, the German
      patients were distinct from the Italian and North American patients with respect
      to DQ2 and from the North American patients with respect to B8-DR3-DQ2 HLA. A
      clinical correlation, e.g. difference in severity or treatability of AIH type 1,
      has yet to be determined.

PMID- 17006991
TI  - Expression pattern of leptin and leptin receptor (OB-R) in human gastric cancer.
AB  - AIM: To examine the expression of leptin and its receptor, OB-R, in normal
      gastric mucosa and neoplasia. METHODS: By immunohistochemical staining using
      specific antibodies, we evaluated the expression of leptin and OB-R in 207
      gastric carcinomas (100 early and 107 advanced carcinomas) and analyzed their
      relationship with clinicopathological features. RESULTS: Both normal gastric
      epithelium and carcinoma cells expressed a significant level of leptin. In cases
      with OB-R staining, carcinoma cells showed OB-R-positive expression, but the
      intensity was weaker than that in normal mucosa. The expression of OB-R showed a
      significant correlation with the level of leptin expression. The expression
      levels of both leptin and OB-R tended to increase as the depth of tumor invasion
      or TMN stage increased (P < 0.01). Lymph node metastasis was detected in 49.5%
      (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and
      the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative
      cases. Both venous and lymphatic invasion also tended to be observed frequently
      in positive tumors as compared with negative tumors. Interestingly, in the 96
      leptin- or OB-R-positive tumors, hematogenous metastasis was detected
      preoperatively in 3 (3.1%) patients. In contrast, none of the carcinomas that
      lacked expression of leptin and OB-R showed hematogenous metastasis. CONCLUSION:
      Overexpression of leptin and expression of OB-R may play a positive role in the
      process of progression in gastric cancer. Functional upregulation of leptin/OB-R
      may have a positive role in the development and initial phase of progression in
      gastric cancer.

PMID- 17006992
TI  - Luminal oxidants selectively modulate electrogenic ion transport in rat colon.
AB  - AIM: To investigate the effects of luminal exposure to H2O(2) and two related
      thiol oxidizing agents on basal and stimulated chloride secretion in native colon
      using electrophysiological and pharmacological approaches. METHODS: Unstripped
      rat distal colon segments were mounted in Ussing chambers. Potential difference,
      calculated resistance and short-circuit current across unstripped colon segments
      were monitored with a dual voltage/current clamp. Paracellular permeability was
      assessed by measuring the mucosa-to-serosa flux of a fluorescent probe (FITC).
      RESULTS: Luminal exposure to hydrogen peroxide transitorily stimulated chloride
      secretion without altering barrier function. This stimulatory effect could be
      blocked by basolateral atropine but not indomethacin. The cysteine and methionine
      oxidizing compounds, phenylarsine oxide and chloramine T respectively, mimicked
      the effect of H2O(2), except for a drop in transcolonic resistance after 30 min.
      In contrast to the observed stimulatory effect on basal secretion, cAMP
      stimulated electrogenic ion transport was blunted by luminal H2O(2). However, the
      Ca(2+)-activated response remained unchanged. CONCLUSION: H2O(2) may be an
      important selective modulator of intestinal ion and water secretion in certain
      pathologic conditions such as inflammation or ischemia-reperfusion by multiple
      mechanisms.

PMID- 17006993
TI  - Timing of laparoscopic cholecystectomy for acute cholecystitis: a prospective non
      randomized study.
AB  - AIM: To study the timing of laparoscopic cholecystectomy for patients with acute
      cholecystitis. METHODS: Between January 2002 and December 2005, all American
      Society of Anesthesiologists classification (ASA) I, II and III patients with
      acute cholecystitis were treated laparoscopically during the urgent (index)
      admission. The patients were divided into three groups according to the timing of
      surgery: (1) within the first 3 d, (2) between 4 and 7 d and (3) beyond 7 d from
      the onset of symptoms. The impact of timing on the conversion rate, morbidity and
      postoperative hospital stay was studied. RESULTS: One hundred and twenty-nine
      patients underwent laparoscopic cholecystectomy for acute cholecystitis during
      the index admission. Thirty six were assigned to group 1, 58 to group 2, and 35
      to group 3. The conversion rate and morbidity for the whole cohort of patients
      were 4.6% and 10.8%, respectively. There was no significant difference in the
      conversion rate, morbidity and postoperative hospital stay between the three
      groups. CONCLUSION: Laparoscopic cholecystectomy for acute cholecystitis during
      the index admission is safe, regardless of the time elapsed from the onset of
      symptoms. This policy can result in an overall shorter hospitalization.

PMID- 17006994
TI  - Long-term outcomes of chronic hepatitis C patients with sustained virological
      response at 6 months after the end of treatment.
AB  - AIM: To assess the clinical, biochemical, and virological outcome during long
      term follow-up of chronic hepatitis C patients with sustained virological
      response following effective antiviral therapy. METHODS: This study was a
      retrospective cohort study including 171 sustained responders defined as HCV RNA
      PCR negative at 6 mo after the end of effective antiviral treatment (SVR-6).
      Clinical signs and symptoms, biochemical hepatic parameters, ultrasonography and
      HCV RNA PCR were followed. RESULTS: Mean follow-up period was 35.38 +/- 22.2 mo
      after the end of treatment. Twenty-seven (15.8%) responders had evidence of
      cirrhosis before treatment. Forty-eight (28.1%), 107 (62.6%) and 6 (3.5%)
      patients were genotype 1, 3, and 6 respectively, while 10 patients (5.8%) were
      unclassified. There were no virological and biochemical relapses during the
      period of follow-up. None of the patients showed evidence of hepatic
      decompensation. However, there were 3 patients (1.8%) developing hepatocellular
      carcinoma at 14, 18, 29 mo after treatment discontinuation, two of whom had
      evidence of cirrhosis prior to therapy. CONCLUSION: The study shows that during a
      follow-up interval for about 3 years in 171 chronic hepatitis C patients with
      sustained viral response after effective antiviral treatment there were no
      evident signs of either biochemical or clinical relapse of liver disease in all
      but three patients who developed hepatocellular carcinoma.

PMID- 17006995
TI  - Comparative study of two bowel preparation regimens for colonoscopy: senna
      tablets vs sodium phosphate solution.
AB  - AIM: To compare the efficacy and acceptance of senna tablet and sodium phosphate
      solution for bowel preparation before colonoscopy. METHODS: One hundred and
      thirty four patients, who needed elective colonoscopy, were randomly allocated to
      take 180 mg senna tablet or 95 mL sodium phosphate solution on the day before
      colonoscopy. The efficacies of both laxatives were compared using the mean
      difference of colon-cleanliness score of the rectum, sigmoid segments, descending
      colon, transverse colon and cecum. The scores were rated by two observers who
      were blinded to the laxatives administered. The higher score means that the colon
      is cleaner. The efficacy of both laxatives were equivalent if the 95% confidence
      interval of the mean difference of the score of colon lie within -1 to +1.
      RESULTS: On intention-to-treat analysis, the mean cleanliness scores in the four
      segments of colon except the cecum were higher in the sodium phosphate group than
      those in senna group (7.9 +/- 1.7 vs 8.3 +/- 1.5, 8.0 +/- 1.8 vs 8.5 +/- 1.4, 7.9
      +/- 2.0 vs 8.5 +/- 1.3, 7.9 +/- 2.0 vs 8.2 +/- 1.4 and 7.2 +/- 1.7 vs 6.9 +/-
      1.4, respectively). The 95% confidence intervals (95% CI) of mean difference in
      each segment of colon were not found to lie within 1 point which indicated that
      their efficacies were not equivalent. The taste of senna was better than sodium
      phosphate solution. Also, senna had fewer side effects. CONCLUSION: The efficacy
      of senna is not equivalent to sodium phosphate solution in bowel preparation for
      colonoscopy, but senna may be considered an alternative laxative.

PMID- 17006996
TI  - Acute effect of smoking on gallbladder emptying and refilling in chronic smokers
      and nonsmokers: a sonographic study.
AB  - AIM: To ultrasonographically evaluate the acute effects of smoking on gallbladder
      contraction and refilling in chronic smokers and nonsmokers. METHODS: Fifteen
      chronic smokers (21-30 years old) and fifteen nonsmokers (21-35 years old)
      participated in this study. Chronic smokers were selected among the volunteers
      who had been smoking for at least 5 years and 10 cigarettes per day (mean
      17.5/d). Examinations were performed in two separate days. In the first day,
      basal gallbladder (GB) volumes of volunteers were measured after 8-h fasting.
      After the examinations, participants had a meal containing at least 30-40 gram
      fat. Gallbladder volume was assessed at 5, 15, 30, 60, 120 and 180 min after the
      meal. In the second day, participants smoked 2 cigarettes after 8-h fasting.
      Then, they had the same meal, and gallbladder measurements were repeated at the
      same time points. Same procedures were applied to both groups. RESULTS: The mean
      starving GB volumes were 23.3 +/- 3.3 mL in the first day, 21.9 +/- 3.0 mL in the
      second day in nonsmoker group and 18.3 +/- 3.0 mL in the first day, 19.5 +/- 2.8
      mL in second day in smoker group. There was no significant difference between
      starving GB volumes. We did not find any significant difference between the GB
      volumes measured at 5, 15, 30, 60, 120 and 180 min in the first and second days
      in nonsmoker group. In smokers, post cigarette GB volume was found significantly
      higher at 5, 15 and 30 min which corresponded to GB contraction phase (P < 0.05).
      Control GB volume measurements were not significantly different between the two
      groups. Post-smoking GB volumes were also not significantly different between the
      two groups. CONCLUSION: Smoking prolongs the maximal GB emptying time both in
      smokers and in nonsmokers though it is not significant. It delays GB contraction
      in chronic smokers and causes a significant decrease in GB emptying volume.
      Smoking causes no significant delay in GB refilling in both smokers and
      nonsmokers. These effects of smoking observed in acute phase result in bile
      stasis in GB. Bile stasis is the underlying cause of most GB disorders in chronic
      process.

PMID- 17006997
TI  - Furazolidone-based triple therapy for H pylori gastritis in children.
AB  - AIM: To evaluate the furazolidone-based triple therapy in children with
      symptomatic H pylori gastritis. METHODS: A prospective and consecutive open trial
      was carried out. The study included 38 patients with upper digestive symptoms
      sufficiently severe to warrant endoscopic investigation. H pylori status was
      defined based both on histology and on positive (13)C-urea breath test. Drug
      regimen was a seven-day course of omeprazole, clarithromycin and furazolidone
      (100 mg, 200 mg if over 30 kg) twice daily. Eradication of H pylori was assessed
      two months after treatment by histology and (13)C -urea breath test. Further
      clinical evaluation was performed 7 d, 2 and 6 mo after the treatment. RESULTS:
      Thirty-eight patients (24 females, 14 males) were included. Their age ranged from
      4 to 17.8 (mean 10.9 +/- 3.7) years. On intent-to-treat analysis (n = 38), the
      eradication rate of H pylori was 73.7% (95% CI, 65.2%-82%) whereas in per
      protocol analysis (n = 33) it was 84.8% (95% CI, 78.5%-91%). All the patients
      with duodenal ulcer (n = 7) were successfully treated (100% vs 56.2% with antral
      nodularity). Side effects were reported in 26 patients (68.4%), mainly vomiting
      (14/26) and abdominal pain (n = 13). Successfully treated dyspeptic patients
      showed improvement in 78.9% of H pylori-negative patients after six months and in
      50% of H pylori-positive patients after six months of treatment. CONCLUSION:
      Triple therapy with furazolidone achieves moderate efficacy in H pylori
      treatment. The eradication rate seems to be higher in patients with duodenal
      ulcer.

PMID- 17006998
TI  - Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric
      patients with Crohn's disease.
AB  - AIM: To investigate the frequency of the common NOD2/CARD15 susceptibility
      variants and two functional polymorphisms of OCTN cation transporter genes in
      Hungarian pediatric patients with Crohn's disease (CD). METHODS: A cohort of 19
      unrelated pediatric and 55 unrelated adult patients with Crohn's disease and 49
      healthy controls were studied. Genotyping of the three common CD-associated
      CARD15 variants (Arg702Trp, Gly908Arg and 1007finsC changes) with the SLC22A4
      1672C-->T, and SLC22A5 -207G-->C mutations was performed by direct sequencing of
      the specific regions of these genes. RESULTS: At least one CARD15 mutation was
      present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in
      controls. Surprisingly, strongly different mutation profile was detected in the
      pediatric versus adult patients. While the G908R and 1007finsC variants were
      18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults,
      and were 1.02% and 3.06% in the controls, respectively. The R702W allele was
      increased approximately two-fold in the adult subjects, while in the pediatric
      group it was only approximately 64% of the controls (9.09% in the adults, 2.63%
      in pediatric patients, and 4.08% in the controls). No accumulation of the OCTN
      variants was observed in any patient group versus the controls. CONCLUSION: The
      frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric
      CD population is high and the profile differs from the adult CD patients, whereas
      the results for SLC22A4 and SLC22A5 mutation screening do not confirm the
      assumption that the carriage of these genotypes means an obligatory
      susceptibility to CD.

PMID- 17006999
TI  - Efficacy of low dose peginterferon alpha-2b with ribavirin on chronic hepatitis
      C.
AB  - AIM: To assess the efficacy of peginterferon alpha 2b at doses of 50 microg
      weekly and 80 microg weekly (based on body weight) plus ribavirin in HCV genotype
      2 and genotype 3 chronic hepatitis C patients. METHODS: During the study period
      of Jan 2002 to Dec 2003, all patients diagnosed as chronic hepatitis C or HCV
      related compensated cirrhosis were treated with peginterferon alpha 2b 50 microg
      S/C weekly (body weight < 60 kg) or 80 microg S/C weekly (body weight > 60 kg)
      plus ribavirin 800 mg/d for 24 wk. RESULTS: Overall 28 patients, 14 patients in
      each group (based on body weight) were treated during the period. Out of 28
      patients, 75% were genotype 3, 18% were genotype 2 and 7% were genotype 1. The
      mean dose of peginterferon alpha 2b was 0.91 microg/kg in group 1 and 1.23
      microg/kg in group 2 respectively. The end of treatment and sustained virologic
      response rates were 82% and 78% respectively. Serious adverse effects were seen
      in 3.5% patients. CONCLUSION: Low dose peginterferon alpha 2b in combination with
      ribavirin for 24 wk is effective in HCV genotype 2 and 3 chronic hepatitis C
      patients.

PMID- 17007000
TI  - Enhanced expression of epidermal growth factor receptor gene in gastric mucosal
      cells by the serum derived from rats treated with electroacupuncture at stomach
      meridian acupoints.
AB  - AIM: To investigate the effect of serum derived from rats treated with
      electroacupuncture at stomach meridian acupoints on the expression of epidermal
      growth factor receptor (EGFR) gene in gastric mucosal cells. METHODS: The stress
      induced gastric mucosal injury in rat model was established by water-immersion
      and restrained stress methods. 52 rats were randomly divided into: normal group
      (n = 8), model group (n = 8), model serum group (n = 12), stomach serum group (n
      = 12), and gallbladder serum group (n = 12). The gastric mucosal cells were
      separated by pronase-EDTA digestion method and incubated with serum. The EGFR
      gene expression in gastric mucosal cells was detected by reverse transcription
      polymerase chain reaction (RT-PCR) method. RESULTS: Compared with normal group
      (0.6860 +/- 0.0594), the serum derived from rats of the stomach group (1.2272 +/-
      0.0813, P = 0.00 < 0.01) and gallbladder group (0.9640 +/- 0.0387, P = 0.00 <
      0.01) had a tendency to enhance the EGFR gene expression in gastric mucosal
      cells. Such tendency existed in the model group (0.7104 +/- 0.0457) but with no
      significant difference (P = 0.495 > 0.05) and in model serum group (0.8516 +/-
      0.0409) with an extremely obvious difference (P = 0.001 < 0.01). Furthermore, the
      EGFR gene expression in stomach serum group was significantly higher than that in
      gallbladder serum group (P = 0.00 < 0.01). CONCLUSION: The present study shows
      that serum derived from rats treated with electroacupuncture at stomach meridian
      acupoints can distinctly increase the EGFR gene expression of gastric mucosal
      cells. Therefore, there is certain meridian specificity in the serum, which could
      provide a proof for the TCM theory "particular relation between meridian and
      internal organ".

PMID- 17007001
TI  - Percutaneous transarterial embolization of extrahepatic arteroportal fistula.
AB  - Arteroportal fistula is a rare cause of prehepatic portal hypertension. A 44-year
      old male with hepatitis virus C infection was admitted for acute variceal
      bleeding. Endoscopy showed the presence of large esophageal varices. The
      ultrasound revealed a mass near the head of pancreas, which was characterized at
      the color-Doppler by a turbulent flow, and arterialization of portal vein flow.
      CT scan of abdomen showed a large aneurysm of the gastroduodenal artery
      communicating into the superior mesenteric vein. The sinusoidal portal pressure
      measured as hepatic vein pressure gradient was normal, confirming the pre-hepatic
      origin of portal hypertension. The diagnosis of extrahepatic portal hypertension
      secondary to arteroportal fistula was established, and the percutaneous
      embolization was performed. Three months later, the endoscopy showed absence of
      esophageal varices and ascites. At the moment, the patient is in good clinical
      condition, without signs of portal hypertension.

PMID- 17007003
TI  - Collision tumor of the rectum: a case report of metastatic gastric adenocarcinoma
      plus primary rectal adenocarcinoma.
AB  - Collision tumors are thought to arise from the accidental meeting and
      interpenetration of two independent tumors. We report here a highly unusual case
      of a 61-year old man who had a unique tumor that was composed of a metastatic
      adenocarcinoma from the stomach to the rectum, which harbored a collision tumor
      of primary rectal adenocarcinoma. The clonalities of the two histologically
      distinct lesions of the rectal mass were confirmed by immunohistochemical and
      molecular analysis. Although histologic examination is the cornerstone in
      pathology, immunohistochemical and molecular analysis can provide evidence
      regarding whether tumors originate from the same clone or different clones. To
      the best of our knowledge, this is the first reported case of such an occurrence.

PMID- 17007002
TI  - Successful outcome after combined chemotherapeutic and surgical management in a
      case of esophageal cancer with breast and brain relapse.
AB  - Esophageal cancer (EC) is a highly lethal disease. Approximately 50% of patients
      present with metastatic EC and most patients with localized EC will have local
      recurrence or develop metastases, despite potentially curative local therapy. The
      most common sites of distant recurrence are represented by lung, liver and bone
      while brain and breast metastases are rare. Usually patients with advanced
      disease are not treated aggressively and their median survival is six months. We
      report a woman patient who developed breast and brain metastases after curative
      surgery. We treated her with a highly aggressive chemotherapeutic and surgical
      combination resulting in a complete remission of the disease even after 11-year
      follow-up. We think that in super selected patients with more than one
      metastasis, when functional status is good and metastases are technically
      resectable, a surgical excision may be considered as a salvage option and
      chemotherapy should be delivered to allow a systemic control.

PMID- 17007004
TI  - Mucosa-associated lymphoid tissue lymphoma of the transverse colon: a case
      report.
AB  - We herein present a case of a 75-year-old female with mucosa-associated lymphoid
      tissue (MALT) lymphoma of the transverse colon with the stage IE (Ann Arbor
      classification). Colonoscopy revealed the tumor's appearance as a IIa plus II c
      like early colon cancer as defined according to the macroscopic classification of
      the Japanese Research Society for Cancer of Colon, Rectum and Anus, measuring
      less than 2 cm in diameter. Histologically, the tumor was diagnosed as MALT
      lymphoma because of the presence of lymphoepithelial lesions consisting of
      diffuse proliferation of atypical lymphocytes and glandular destruction. The
      majority of these lymphocytes immunohistochemically stained for the B-lymphocyte
      marker. The patient first underwent H pylori eradication therapy with Lansap.
      However, the tumor size gradually increased over the next 4 mo and the patient
      eventually underwent surgical resection. The operative procedure included a
      partial colectomy with dissection of the paracolic lymph nodes. The tumor
      measured 45 mm multiply 30 mm in diameter and histological examination showed
      that the lymphoma cells had infiltrated the muscle layer of the colon without
      nodal involvement. The patient has had no recurrence postoperatively without any
      chemotherapy.

PMID- 17007005
TI  - Unusual site of recurrent musculoskeletal hydatid cyst: case report and brief
      review of the literature.
AB  - A case of a large multiplex recurrent hydatid cyst involving the left gluteal
      muscle and the left iliopsoas, accompanied with degeneration of the musculature
      of the left upper leg is presented along with a review of the relevant
      literature. Very few such cases have been reported worldwide. The presented case
      is also distinguished by the involvement of muscles of distant anatomic areas.

PMID- 17007006
TI  - An alternative surgical approach to a difficult case of Mirizzi syndrome: a case
      report and review of the literature.
AB  - Mirizzi syndrome (MS) is an uncommon complication of gallstone disease and occurs
      in approximately 1% of all patients suffering from cholelithiasis. The syndrome
      is characterized by extrinsic compression of the common hepatic duct frequently
      resulting in clinical presentation of intermittent or constant jaundice. Most
      cases are not identified preoperatively. Surgery is the indicated treatment for
      patients with MS. We report here a 71-year-old male patient referred to the
      surgical outpatient department for diffuse upper abdominal pain and mild jaundice
      (bilirubin rate: 4.2 mg/dL). Ultrasound examination revealed a stone in the
      cystic duct compressing the common hepatic duct. The patient had a history of
      gastrectomy for gastric ulcer 30 years ago. MRCP revealed a stone impacted in the
      cystic duct causing obstruction of the common hepatic duct by extrinsic
      compression. With these findings the preoperative diagnosis was indicative of MS.
      At laparotomy a moderately shrunken gallbladder was found embedded in adhesions
      containing a large stone which was palpable in the common bile duct. The anterior
      wall of the body of the gallbladder was opened by an incision which extended
      longitudinally along the gallbladder towards the common bile duct. The stone
      measuring 3.0 cm in diameter, was then removed setting astride a large
      communication with the common bile duct. A Roux-en-Y cholecysto-choledocho
      jejunostomy was performed. The subhepatic region was drained. The patient had an
      uneventful recovery. He was discharged eleven days after operation and remained
      well after a 30-mo follow-up.

PMID- 17007007
TI  - Portal venous gas and thrombosis in a Chinese patient with fulminant Crohn's
      colitis: a case report with literature review.
AB  - Ever since its earliest reports, portal venous gas (PVG) has been associated with
      numerous intraabdominal catastrophes and has served as an indication for urgent
      surgical exploration. It is traditionally regarded to be an ominous finding of
      impending death, with highest mortality reported in patients with underlying
      bowel ischemia. Today, computed tomography has demonstrated a wider range of
      clinical conditions associated with PVG, some of which are "benign" and do not
      necessarily require surgery, unless when there are signs of intraabdominal
      catastrophe or systemic toxicity. One of these "benign" conditions is Crohn's
      disease. The present report describes a 19-year-old Chinese boy with Crohn's
      pancolitis who presented with septic shock associated with PVG and portal vein
      thrombosis, and was successfully managed surgically. To our knowledge, this is
      the first report of PVG and portal vein thrombosis associated with Crohn's
      disease in a Chinese patient. In addition, we have also reviewed the reports of
      another 18 Crohn's patients with PVG previously described in the English
      literature. Specific predisposing factors for PVG were identified in 8 patients,
      including barium enema, colonoscopy, blunt abdominal trauma, and enterovenous
      fistula. The patients who developed PVG following barium enema and blunt trauma
      were all asymptomatic and no specific treatment was necessary. Eleven patients
      (58%) who presented with signs of intraabdominal catastrophe or systemic toxicity
      required either immediate or eventual surgery. The overall mortality rate among
      the 19 patients was only 11%. The present literature review has shown that the
      finding of PVG associated with Crohn's disease does not always mandate surgical
      intervention. It is the clinical features and the related complications that
      ultimately determine the treatment approaches. The overall outcome of PVG
      associated with Crohn's disease has been favourable.

PMID- 17007008
TI  - Is there an alternative therapy to cyanoacrylate injection for safe and effective
      obliteration of bleeding gastric varices?

PMID- 17007009
TI  - Immune response to H. pylori.
AB  - The gastric mucosa separates the underlying tissue from the vast array of
      antigens that traffic through the stomach lumen. While the extreme pH of this
      environment is essential in aiding the activation of enzymes and food digestion,
      it also renders the gastric epithelium free from bacterial colonization, with the
      exception of one important human pathogen, H. pylori. This bacterium has
      developed mechanisms to survive the harsh environment of the stomach, actively
      move through the mucosal layer, attach to the epithelium, evade immune responses,
      and achieve persistent colonization. While a hallmark of this infection is a
      marked inflammatory response with the infiltration of various immune cells into
      the infected gastric mucosa, the host immune response is unable to clear the
      infection and may actually contribute to the associated pathogenesis. Here, we
      review the host responses involved during infection with H. pylori and how they
      are influenced by this bacterium.

PMID- 17007010
TI  - H pylori and host interactions that influence pathogenesis.
AB  - H. pylori is probably the most prevalent human pathogen worldwide. Since it was
      initially suggested in 1983 by Marshall and Warren to be implicated in gastritis
      and peptic ulcer disease, H. pylori has also been implicated in gastric carcinoma
      and was classified as a class I carcinogen. In the last two decades, a noteworthy
      body of research has revealed the multiple processes that this gram negative
      bacterium activates to cause gastroduodenal disease in humans. Most infections
      are acquired early in life and may persist for the life of the individual. While
      infected individuals mount an inflammatory response that becomes chronic, along
      with a detectable adaptive immune response, these responses are ineffective in
      clearing the infection. H. pylori has unique features that allow it to reside
      within the harsh conditions of the gastric environment, and also to evade the
      host immune response. In this review, we discuss the various virulence factors
      expressed by this bacterium and how they interact with the host epithelium to
      influence pathogenesis.

PMID- 17007011
TI  - Interleukin-12 and Th1 immune response in Crohn's disease: pathogenetic relevance
      and therapeutic implication.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory
      disorders of the gastrointestinal tract that share clinical and pathological
      characteristics. The most accredited hypothesis is that both CD and UC result
      from a deregulated mucosal immune response to normal constituents of the gut
      microflora. Evidence, however, indicates that the main pathological processes in
      these two diseases are distinct. In CD, the tissue-damaging inflammatory reaction
      is driven by activated type 1 helper T-cell (Th1), whereas a humoral response
      predominates in UC. Consistently, a marked accumulation of macrophages making
      interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC
      mucosa. Preliminary studies also indicate that administration of a monoclonal
      antibody blocking the IL-12/p40 subunit can be useful to induce and maintain
      clinical remission in CD patients. Notably, the recently described IL-23 shares
      the p40 subunit with IL-12, raising the possibility that the clinical benefit of
      the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23
      activity. This review summarizes the current information on the expression and
      functional role of IL-12 and IL-12-associated signaling pathways both in patients
      with CD and experimental models of colitis, thus emphasizing major differences
      between IL-12 and IL-23 activity on the development of intestinal inflammation.

PMID- 17007013
TI  - Assessing risks for gastric cancer: new tools for pathologists.
AB  - Although the Sydney Systems (original and updated) for the classification of
      gastritis have contributed substantially to the uniformity of the reporting of
      gastric conditions, they lack immediacy in conveying to the user information
      about gastric cancer risk. In this review, we summarize the current understanding
      of the gastric lesions associated with an increased risk for cancer, and present
      the rationale for a proposal for new ways of reporting gastritis. In addition to
      the traditional histopathological data gathered and evaluated according to the
      Sydney System rules, pathologists could add an assessment expressed as grading
      and staging of the gastric inflammatory and atrophic lesions and integrate these
      findings with pertinent laboratory information on pepsinogens and gastrin levels.
      Such an integrated report could facilitate clinicians' approach to the management
      of patients with gastric conditions.

PMID- 17007014
TI  - Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells.
AB  - AIM: To investigate the intracellular apoptotic signals engaged by resveratrol in
      three gastric adenocarcinoma cancer cell lines, two of which (AGS and SNU-1)
      express p53 and one (KATO-III) with deleted p53. METHODS: Nuclear fragmentation
      was used to quanti-tate apoptotic cells; caspase activity was determined by
      photometric detection of cleaved substrates; formation of oxidized cytochrome C
      was used to measure cytochrome C activity, and Western blot analysis was used to
      determine protein expression. RESULTS: Gastric cancer cells, irrespective of
      their p53 status, responded to resveratrol with fragmentation of DNA and cleavage
      of nuclear lamins A and B and PARP. Resveratrol, however, has no effect on
      mitochondria-associated apoptotic proteins Bcl-2, Bcl-xl, Bax, Bid or
      Smac/Diablo, and did not promote sub-cellular redistribution of cytochrome C,
      indicating that resveratrol-induced apoptosis of gastric carcinoma cells does not
      require breakdown of mitochondrial membrane integrity. Resveratrol up-regulated
      p53 protein in SNU-1 and AGS cells but there was a difference in response of
      intracellular apoptotic signals between these cell lines. SNU-1 cells responded
      to resveratrol treatment with down-regulation of survivin, whereas in AGS and
      KATO-III cells resveratrol stimulated caspase 3 and cytochrome C oxidase
      activities. CONCLUSION: These findings indicate that even within a specific
      cancer the intracellular apoptotic signals engaged by resveratrol are cell type
      dependent and suggest that such differences may be related to differentiation or
      lack of differentiation of these cells.

PMID- 17007012
TI  - Upper gastrointestinal function and glycemic control in diabetes mellitus.
AB  - Recent evidence has highlighted the impact of glycemic control on the incidence
      and progression of diabetic micro- and macrovascular complications, and on
      cardiovascular risk in the non-diabetic population. Postprandial blood glucose
      concentrations make a major contribution to overall glycemic control, and are
      determined in part by upper gastrointestinal function. Conversely, poor glycemic
      control has an acute, reversible effect on gastrointestinal motility. Insights
      into the mechanisms by which the gut contributes to glycemia have given rise to a
      number of novel dietary and pharmacological strategies designed to lower
      postprandial blood glucose concentrations.

PMID- 17007016
TI  - Hemoglobin induces colon cancer cell proliferation by release of reactive oxygen
      species.
AB  - AIM: To study whether hemoglobin could amplify colon cancer cell proliferation
      via reactive oxygen species (ROS) production. METHODS: Colon cancer cell line HT
      29 was grown in the conventional method using RPMI1640 media. The viability of
      the cells was measured using the colorimetric MTT [3-(4, 5-dimethylthiazol-2-yl)
      2, 5-diphenyltetrazolium bromide] assay after adding hemoglobin. We determined
      reactive oxygen species levels to be indicators of oxidative stress in HT 29 cell
      lines with and without hemoglobin and/or 5-fluorouracil (5-FU), 5'-deoxy-5
      fluorouridine (5-DFUR) using fluorometric dichlorofluorescin diacetate (DCFH-DA)
      assay. RESULTS: Cellular proliferation was increased with hemoglobin in a
      concentration-dependent manner. A significant increment on ROS levels was found
      in HT 29 cells following hemoglobin incubation. The cytotoxic effects of 5-FU and
      5-DFUR were significantly blunted by administration of hemoglobin. There was a
      slight increase of peroxiredoxin 1, superoxide dismutase 1 concentration
      according to different hemoglobin concentrations. CONCLUSION: Hemoglobin has a
      cellular proliferative effect on HT-29 colon cancer cell line by production of
      ROS. Also, hemoglobin abates cytotoxic effects of chemotherapeutic agents such as
      5-FU and 5-DFUR.

PMID- 17007017
TI  - Promoter hypomethylation and reactivation of MAGE-A1 and MAGE-A3 genes in
      colorectal cancer cell lines and cancer tissues.
AB  - AIM: To verify the expression and methylation status of the MAGE-A1 and MAGE-A3
      genes in colorectal cancer tissues and cancer cell lines. METHODS: We evaluated
      promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis
      and methylation-specific PCR (MS-PCR), as well as sequencing analysis, after
      sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer
      tissues. RESULTS: Of the 32 cell lines, MAGE-A1 and MAGE-A3 expressions were
      observed in 59% and 66%, respectively. Subsequent to sodium bisulfite
      modification and MS-PCR analysis, the promoter hypomethylation of MAGE-A1 and
      MAGE-A3 was confirmed in both at 81% each. Promoter hypomethylation of MAGE-A1
      and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%,
      respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding
      normal tissues were observed in 2% and 6%, respectively. CONCLUSION: The promoter
      hypomethylation of MAGE genes up-regulates its expression in colorectal
      carcinomas as well as in gastric cancers and might play a significant role in the
      development and progression of human colorectal carcinomas.

PMID- 17007015
TI  - Tyrosine kinase of insulin-like growth factor receptor as target for novel
      treatment and prevention strategies of colorectal cancer.
AB  - AIM: To investigate the antineoplastic potency of the novel insulin-like growth
      factor 1 receptor (IGF-1R) tyrosine kinase inhibitor (TKI) NVP-AEW541 in cell
      lines and primary cell cultures of human colorectal cancer (CRC). METHODS: Cells
      of primary colorectal carcinomas were from 8 patients. Immunostaining and crystal
      violet staining were used for analysis of growth factor receptor protein
      expression and detection of cell number changes, respectively. Cytotoxicity was
      determined by measuring the release of the cytoplasmic enzyme lactate
      dehydrogenase (LDH). The proportion of apoptotic cells was determined by
      quantifying the percentage of sub-G1 (hypodiploid) cells. Cell cycle status
      reflected by the DNA content of the nuclei was detected by flow cytometry.
      RESULTS: NVP-AEW541 dose-dependently inhibited the proliferation of colorectal
      carcinoma cell lines and primary cell cultures by inducing apoptosis and cell
      cycle arrest. Apoptosis was characterized by caspase-3 activation and nuclear
      degradation. Cell cycle was arrested at the G1/S checkpoint. The NVP-AEW541
      mediated cell cycle-related signaling involved the inactivation of Akt and
      extracellular signal-regulated kinase (ERK) 1/2, the upregulation of the cyclin
      dependent kinase inhibitors p21(Waf1/CIP1) and p27(Kip1), and the downregulation
      of the cell cycle promoter cyclin D1. Moreover, BAX was upregulated during NVP
      AEW541-induced apoptosis, whereas Bcl-2 was downregulated. Measurement of LDH
      release showed that the antineoplastic effect of NVP-AEW541 was not due to
      general cytotoxicity of the compound. However, augmented antineoplastic effects
      were observed in combination treatments of NVP-AEW541 with either 5-FU, or the
      EGFR-antibody cetuximab, or the HMG-CoA-reductase inhibitor fluvastatin.
      CONCLUSION: IGF-1R-TK inhibition is a promising novel approach for either mono-
      or combination treatment strategies of colorectal carcinoma and even for CRC
      chemoprevention.

PMID- 17007018
TI  - H. pylori infection and reflux oesophagitis: a case-control study.
AB  - AIM: To examine the relationship between H. pylori and gastro-oesophageal reflux
      disease (GORD) in Iran. METHODS: In this study 51 GORD patients (referred to
      endoscopy at Taleghani hospital) were compared with 49 age-sex matched controls.
      Diagnosis of H. pylori was made by gastric mucosal biopsy and rapid urease test
      (positive if the result of one or both diagnostic methods was positive). Updated
      Sydney system was used to report histopathological changes. RESULTS: The
      frequency of H. pylori infection based on rapid urease test and histology was
      88.2% (45) in patients and 77.6% (38) in controls, which showed no significant
      difference. The frequency of H. pylori infection was significantly higher in the
      antrum than in the corpus and cardia. The mean activity, inflammation, and
      gastritis scores were also higher in the antrum of patients than in the antrum of
      controls. The mean scores were significantly higher in the corpus of controls
      than in the corpus of patients. Diffuse active gastritis was observed in a
      significantly larger number of controls, while the frequency of diffuse chronic
      gastritis was higher in patients. There was no significant difference in the
      frequency of other histological findings between patients and controls.
      CONCLUSION: H. pylori infection cannot prevent GORD in this region.

PMID- 17007019
TI  - Natural maternal transmission of H. pylori in Mongolian gerbils.
AB  - AIM: To investigate maternal H. pylori infection status to determine the
      potential of maternal transmission. METHODS: In the present study, we examined
      these issues in an experimental murine model, which is a Mongolian gerbil model
      that has been reported as an optimal laboratory animal model to study H. pylori.
      Pregnant Mongolian gerbils, infected experimentally with H. pylori, were divided
      into as four groups. Following the experimental design, the stomachs of the
      mother and litters were isolated and assessed for transmission of H. pylori at
      the prenatal period, parturition day, 1-wk old and 3-wk old respectively.
      Bacterial culture and polymerase chain reaction (PCR) were used to examine the
      presence of transmitted H. pylori. RESULTS: All litters showed no transmission of
      H. pylori during pregnancy and at parturition day. However, they revealed 33.3%
      and 69.6% at 1-wk and 3-wk of age respectively by PCR. CONCLUSION: These results
      suggested that vertical infection during the prenatal period or delivery
      procedure is unlikely as a route of mother-to-child H pylori infection. It may be
      that H. pylori is acquired through breast-feeding, contaminated saliva and fecal
      oral transmission during co-habitation.

PMID- 17007020
TI  - Mechanical behavior of colonic anastomosis in experimental settings as a measure
      of wound repair and tissue integrity.
AB  - AIM: To determine the mechanical properties of anastomotic colonic tissue in
      experimental settings and therefore give a measure of wound healing. METHODS:
      Thirty-six male Wistar rats were used as experimental models of anastomotic
      tissue integrity. On the 5th post-operative day, the tensile strength was
      measured by application of an axial force, providing a quantitative measure of
      anastomotic dehiscence and leakage. RESULTS: Diagrams of the load as a function
      of the time [P = P (t)] and of the displacement also as a function of time [Delta
      s = Delta s (t)] were recorded for each test, permitting the design of the load
      versus the displacement diagram and thus providing significant data about the
      critical values of anastomotic failure. Quantitative data were obtained
      concerning the anastomotic strength of both control specimens (healthy rats), as
      well as specimens from non-healthy rats for comparison. CONCLUSION: This
      experimental model provides an excellent method of measuring anastomotic
      strength. Despite the relative small number of specimens used, this method
      provides an accurate way of measuring wound repair. More experimental
      measurements need to be performed to correlate emerging tensile strength values
      to anastomotic failure.

PMID- 17007021
TI  - Localization of ANP-synthesizing cells in rat stomach.
AB  - AIM: To study the morphological positive expression of antrial natriuretic
      peptide (ANP)-synthesizing cells and ultrastructural localization and the
      relationship between ANP-synthesizing cells and microvessel density in the
      stomach of rats and to analyze the distribution of the three histologically
      distinct regions of ANP-synthesizing cells. METHODS: Using immunohistochemical
      techniques, we studied positive expression of ANP-synthesizing cells in rat
      stomach. A postembedding immunogold microscopy technique was used for
      ultrastructural localization of ANP-synthesizing cells. Microvessel density in
      the rat stomach was estimated using tannic acid-ferric chloride (TAFC) method
      staining. Distribution of ANP-synthesizing cells were studied in different
      regions of rat stomach histochemically. RESULTS: Positive expression of ANP
      synthesizing cells were localized in the gastric mucosa of rats. Localization of
      ANP-synthesizing cells identified them to be enterochrochromaffin cells (EC) by
      using a postembedding immunogold electron microscopy technique. EC cells were in
      the basal third of the cardiac mucosa region. ANP-synthesizing cells existed in
      different regions of rat stomach and its density was largest in the gastric
      cardiac region, and the distribution order of ANP-synthesizing cells in density
      was cardiac region, pyloric region and fundic region in mucosa layer. We have
      also found a close relationship between ANP-synthesizing cells and microvessel
      density in gastric mucosa of rats using TAFC staining. CONCLUSION: ANP
      synthesizing cells are expressed in the gastric mucosa. EC synthesize ANP. There
      is a close relationship between ANP-synthesizing cells and microvessel density in
      gastric mucosa of rats. The distribution density of ANP-synthesizing cells is
      largest in the gastric cardiac region.

PMID- 17007023
TI  - Expressions of sonic hedgehog, patched, smoothened and Gli-1 in human intestinal
      stromal tumors and their correlation with prognosis.
AB  - AIM: To investigate the role that the hedgehog (Hh) signaling pathway, which
      includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays
      in human gastrointestinal stromal tumors (GISTs). METHODS: Surgically resected
      specimens from patients with GISTs, leiomyomas and schwannomas were examined by
      immunohistochemical staining for aberrant expression of hedgehog signaling
      components, Shh, Ptc, Smo and Gli-1, respectively. RESULTS: In GISTs, 58.1% (18
      of 31), 77.4% (24 of 31), 80.6% (25 of 31) and 58.1% (18 of 31) of the specimens
      stained positive for Shh, Ptc, Smo and Gli-1, respectively. In leiomyomas, 92.3%
      (12 of 13), 92.3% (12 of 13), 69.2% (9 of 13) and 92.3% (12 of 13) stained
      positive for Shh, Ptc, Smo and Gli-1, respectively. In schwannomas, 83.3% (5 of
      6), 83.3% (5 of 6), 83.3% (5 of 6) and 100% (6 of 6) stained positive for Shh,
      Ptc, Smo and Gli-1, respectively. Immunohistochemistry revealed that the
      expressions of Shh and Gli-1 were significantly higher in leiomyomas than in
      GISTs (P < 0.05, respectively). Shh expression strongly correlated with the grade
      of tumor risk category and with tumor size (P < 0.05, respectively). However, the
      expressions of Ptc and Smo did not correlate with histopathological
      differentiation. CONCLUSION: These results suggest that the Hh signaling pathway
      may play an important role in myogenic differentiation and the malignant
      potential of human intestinal stromal tumors.

PMID- 17007022
TI  - Mutifactorial analysis of risk factors for reduced bone mineral density in
      patients with Crohn's disease.
AB  - AIM: To determine the prevalence of osteoporosis in a cohort of patients with
      Crohn's disease (CD) and to identify the relative significance of risk factors
      for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M,
      166 F) with CD were studied. Bone mineral density (BMD) was measured at the
      lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by
      measuring bone specific alkaline phosphatase (BSAP) and bone resorption by
      measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX).
      RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the
      lumbar spine and/or hip. NTX levels were significantly higher in the patients
      with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly
      different. Independent risk factors for osteoporosis at either the lumbar spine
      or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P <
      0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37%
      of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our
      results confirm that osteoporosis is common in patients with CD and suggest that
      increased bone resorption is the mechanism responsible for the bone loss.
      However, less than half of the reduction in BMD can be attributed to risk factors
      such as corticosteroid use and low BMI and therefore remains unexplained.

PMID- 17007024
TI  - Treatment of hepatitis C virus genotype 4 with peginterferon alfa-2a: impact of
      bilharziasis and fibrosis stage.
AB  - AIM: To evaluate pegylated interferon alpha2a (PegIFN-alpha2a) in Egyptian
      patients with HCV genotype 4, and the impact of pretreatment viral load, co
      existent bilharziasis and histological liver changes on response rate. METHODS: A
      total of 73 naive patients (61 with history of bilharziasis) with compensated
      chronic HCV genotype 4 were enrolled into: group A (38 patients) who received 180
      mg PegIFN-alpha2a subcutaneously once weekly for a year and group B (35 patients)
      received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at
      a dose of 1200 mg. Patients were followed for 72 wk and sustained response was
      assessed. RESULTS: Significant improvement in both end of treatment response
      (ETR) (P < 0.002) and sustained response (SR) (P < 0.05) was noted with pegylated
      interferon, where ETR was achieved in 29 (76.3%) and 14 patients (40%) in both
      groups respectively, and 25 patients in group A (65.8%) and 9 (25.7%) in group B
      could retain negative viraemia by the end of follow up period. Sustained
      virological response (SVR) showed a significant negative correlation with age and
      positive correlation with pretreatment inflammation in patients receiving PegIFN.
      Viral clearance after 3 mo of therapy was associated with high incidence of ETR
      and SR (P < 0.001), but without significant difference between both forms of
      interferon. Significant improvement in response was achieved in patients with
      high grade fibrosis (grade 3 and 4) with PegIFN-alpha2a, where SR was seen in 5
      out of 13 patients in group A, but none in group B. There was no significant
      difference in response between bilharzial and non-bilharzial patients in both
      groups. In terms of safety and tolerability, neutropenia was the predominant side
      effect; both drugs were comparable. CONCLUSION: PegIFN-alpha2a combined with
      ribavirin results in improvement in sustained response in HCV genotype 4,
      irrespective of history of bilharzial infestation.

PMID- 17007025
TI  - Endoscopic mucosal resection of large hyperplastic polyps in 3 patients with
      Barrett's esophagus.
AB  - AIM: To report the endoscopic treatment of large hyperplastic polyps of the
      esophagus and esophago-gastric junction (EGJ) associated with Barrett's esophagus
      (BE) with low-grade dysplasia (LGD), by endoscopic mucosal resection (EMR).
      METHODS: Cap fitted EMR (EMR-C) was performed in 3 patients with hyperplastic
      inflammatory polyps (HIPs) and BE. RESULTS: The polyps were successfully removed
      in the 3 patients. In two patients, with short segment BE (SSBE) (<= 3 cm), the
      metaplastic tissue was completely excised. A 2 cm circumferential EMR was
      performed in one patient with a polyp involving the whole EGJ. A simultaneous EMR
      C of a BE-associated polypoid dysplastic lesion measuring 1 cm multiply 10 cm,
      was also carried out. In the two patients, histologic assessment detected LGD in
      BE. No complications occurred. Complete neosquamous re-epithelialization occurred
      in the two patients with SSBE. An esophageal recurrence occurred in the remaining
      one and was successfully retreated by EMR. CONCLUSION: EMR-C appears to be a safe
      and effective method for treating benign esophageal mucosal lesions, allowing
      also the complete removal of SSBE.

PMID- 17007026
TI  - Assessment of oxidative stress in chronic pancreatitis patients.
AB  - AIM: To assess the levels of antioxidant capacity and oxidative damage in blood
      of chronic pancreatitis (CP) patients in comparison with those in healthy control
      subjects, by using several different analytical techniques. METHODS: Thirty-five
      CP patients and 35 healthy control subjects were investigated prospectively with
      respect to plasma levels of thiols, ferric reducing ability of plasma (FRAP, i.e.
      antioxidant capacity), levels of protein carbonyls and thiobarbituric acid
      reactive substances (TBARS). Additionally, we evaluated the production of
      reactive oxygen species (ROS) in whole blood. RESULTS: The antioxidative thiols
      including cysteine, cysteinylglycine and glutathione were significantly lower in
      CP patients. In addition, the non-enzymatic antioxidant capacity was
      significantly lower in CP patients, which correlated with the amount of oxidative
      protein (protein carbonyls) and the extent of lipid damage (TBARS), both were
      significantly higher in CP patients. The ROS production in whole blood after
      stimulation with phorbol 12-myritate 13-acetaat, demonstrated a strong tendency
      to produce more ROS in CP patients. CONCLUSION: Oxidative stress may contribute
      to the pathogenesis of chronic pancreatitis by decreasing antioxidant capacity
      and increasing oxidative damage in CP patients may be a rationale for
      intervention with antioxidant therapy.

PMID- 17007027
TI  - Chronic Epstein-Barr virus-related hepatitis in immunocompetent patients.
AB  - AIM: To investigate reactivated Epstein-Barr virus (EBV) infection as a cause for
      chronic hepatitis. METHODS: Patients with occasionally established elevated serum
      aminotransferases were studied. HIV, HBV and HCV-infections were excluded as well
      as any other immunosuppressive factors, metabolic or toxic disorders. EBV viral
      capsid antigen (VCA) IgG and IgM, EA-R and EA-D IgG and Epstein-Barr nuclear
      antigen (EBNA) were measured using IFA kits. Immunophenotyping of whole blood was
      performed by multicolor flow cytometry. CD8(+) T cell responses to EBV and PHA
      were determined according to the intracellular expression of IFN-gamma. RESULTS:
      The mean alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGTP)
      values exceeded twice the upper normal limit, AST/ALT ratio < 1. Serology tests
      showed reactivated EBV infection in all patients. Absolute number and percentages
      of T, B and NK cells were within the reference ranges. Fine subset analysis, in
      comparison to EBV(+) healthy carriers, revealed a significant decrease of naive T
      cells (P < 0.001), accompanied by increased percentage of CD45RA(-) (P < 0.0001),
      and terminally differentiated CD28(-)CD27(-)CD8(+) T cells (P < 0.01). Moderately
      elevated numbers of CD38 molecules on CD8(+) T cells (P < 0.05) proposed a low
      viral burden. A significantly increased percentage of CD8(+) T cells expressing
      IFN-gamma in response to EBV and PHA stimulation was registered in patients, as
      compared to controls (P < 0.05). Liver biopsy specimens from 5 patients revealed
      nonspecific features of low-grade hepatitis. CONCLUSION: Chronic hepatitis might
      be a manifestation of chronic EBV infection in the lack of detectable immune
      deficiency; the expansion of CD28(-)CD27(-) and increase of functional EBV
      specific CD8(+) T cells being the only surrogate markers of viral activity.

PMID- 17007028
TI  - Association of promoter polymorphism of the CD14 C (-159) T endotoxin receptor
      gene with chronic hepatitis B.
AB  - AIM: To investigate whether single-nucleotide polymorphisms in the promoter
      regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic
      hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established
      diagnosis of chronic hepatitis B and 126 healthy subjects served as a control
      population. The CD 14 C (-159) T polymorphism was investigated using an allele
      specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B
      patients and 75% of controls were heterozygous for CT genotype. The difference
      between the chronic hepatitis B and control groups was statistically significant
      [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six
      percent of chronic hepatitis B and patients 12.3% of the control group were
      heterozygous for TT genotype. The difference between groups was not statistically
      significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four
      percent of chronic hepatitis B patients and 12.7% of control were homozygote for
      CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele
      C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency
      of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR
      = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a
      risk factor for chronic hepatitis B. CC homozygote genotype is protective for
      hepatitis B. Lack of heterozygosis of genotype CT is a risk factor for chronic
      hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These
      findings show the role of a single-nucleotide polymorphism at CD14/-159 on the
      development of chronic hepatitis B. Endotoxin susceptibility may play a role in
      the pathogenesis of chronic hepatitis B.

PMID- 17007029
TI  - Inhibition of hepatitis B virus production by Boehmeria nivea root extract in
      HepG2 2.2.15 cells.
AB  - AIM: To explore the anti-hepatitis B virus (HBV) effects of Boehmeria nivea (B.
      nivea) root extract (BNE) by using the HepG2 2.2.15 cell model system. METHODS:
      Hepatitis B surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg), and HBV
      DNA were measured by using ELISA and real-time PCR, respectively. Viral DNA
      replication and RNA expression were determined by using Southern and Northern
      blot, respectively. RESULTS: In HepG2 2.2.15 cells, HBeAg (60%, P < 0.01) and
      particle-associated HBV DNA (> 99%, P < 0.01) secretion into supernatant were
      significantly inhibited by BNE at a dose of 100 mg/L, whereas the HBsAg was not
      inhibited. With different doses of BNE, the reduced HBeAg was correlated with the
      inhibition of HBV DNA. The anti-HBV effect of BNE was not caused by its
      cytotoxicity to cells or inhibition of viral DNA replication and RNA expression.
      CONCLUSION: BNE could effectively reduce the HBV production and its anti-HBV
      machinery might differ from the nucleoside analogues.

PMID- 17007030
TI  - Resection of non-cystic adenocarcinoma in pancreatic body and tail.
AB  - AIM: To report the outcome of Chinese patents with non-cystic adenocarcinoma in
      pancreatic body and tail (NCAPBT) after resection and to discuss its surgical
      strategy. METHODS: Resection of NCAPBT was performed in eight Chinese patients
      with complete clinical-pathological data in our hospital from January 2000 to May
      2004. The surgical strategy was explored by analyzing the results of these
      patients. RESULTS: The resection rate of NCAPBT in patients without back pain was
      higher than that in patients with back pain (66.67% vs 20%, 2/3 vs 1/5). The
      prognosis in the group receiving palliative resection was poorer than that in the
      group receiving curative resection. The median survival time was 12 mo in the
      curative resection group and 6 mo in the palliative resection group,
      respectively. CONCLUSION: The overall survival time of the Chinese patients with
      NCAPBT is dismal. The Chinese patients after curative resection of NCAPBT have a
      longer survival time. The Chinese NCAPBT patients with back pain trend to have a
      lower curative resection rate, but back pain should not be considered a
      contraindication for curative resection.

PMID- 17007031
TI  - Hepatic intra-arterial infusion of yttrium-90 microspheres in the treatment of
      recurrent hepatocellular carcinoma after liver transplantation: a case report.
AB  - Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after
      liver transplantation. Recurrence is associated with a mortality rate exceeding
      75%. Approximately one-third of recurrences develop in the transplanted liver and
      are therefore amenable to local therapy. A variety of treatment modalities have
      been reported including resection, transarterial chemo-embolization (TACE),
      radiofrequency ablation (RFA), ethanol ablation, cryoablation, and external beam
      irradiation. Goals of treatment are tumor control and the minimization of toxic
      effect to functional parenchyma. Efficacy of treatment is mitigated by the need
      for ongoing immunosuppression. Yttrium-90 microspheres have been used as a
      treatment modality both for primary HCC and for pre-transplant management of HCC
      with promising results. Twenty-two months after liver transplantation for
      hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence
      of HCC in his transplant allograft. Treatment of multiple right lobe lesions with
      anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal
      recurrence in the remaining liver allograft was treated with hepatic intra
      arterial infusion of yttrium-90 microspheres (SIR-Spheres, Sirtex Medical Inc.,
      Lake Forest, IL, USA). Efficacy was demonstrated by tumor necrosis on imaging and
      a decrease in alpha-fetoprotein (AFP) level. There were no adverse consequences
      of initial treatment.

PMID- 17007032
TI  - Successful management of hepatic artery pseudoaneurysm complicating chronic
      pancreatitis by stenting.
AB  - A 41-year old alchoholic male with a history of chronic pancreatitis was admitted
      for nausea, vomiting and weight loss. Angiogram was performed and demonstrated an
      aneurysmal sac with a narrow neck originating from the inferior aspect of the
      distal portion of the proper hepatic artery. The origin of the pseudoaneurysm was
      covered with a 5 mm multiply 2.5 cm Viabahn cover stent (Gore). A repeat
      angiogram showed some leak and a second stent (6 mm multiply 2.3 cm) was deployed
      and overlapped with the first stent by 3 mm. Contrast was injected and a repeat
      angiogram demonstrated complete exclusion of the aneurysm. A repeat computerized
      axial tomography (CAT) scan of the abdomen after 24 h showed successful stenting.
      The patient had an uneventful post-operative course.

PMID- 17007033
TI  - Obstructive jaundice due to hepatobiliary cystadenoma or cystadenocarcinoma.
AB  - Hepatobiliary cystadenomas (HBC) and cystadenocarcinomas are rare cystic lesions.
      Most patients with these lesions are asymptomatic, but presentation with
      obstructive jaundice may occur. The first patient presented with intermittent
      colicky pain and recurrent obstructive jaundice. Imaging studies revealed a
      polypoid lesion in the left hepatic duct. The second patient had recurrent
      jaundice and cholangitis. Endoscopic retrograde cholangiopancreatography (ERCP)
      showed a cystic lesion at the confluence of the hepatic duct. In the third
      patient with intermittent jaundice and cholangitis, cholangioscopy revealed a
      papillomatous structure protruding into the left bile duct system. In the fourth
      patient with obstructive jaundice, CT-scan showed slight dilatation of the
      intrahepatic bile ducts and dilatation of the common bile duct of 3 cm. ERCP
      showed filling of a cystic lesion. All patients underwent partial liver
      resection, revealing HBC in the specimen. In the fifth patient presenting with
      obstructive jaundice, ultrasound examination showed a hyperechogenic cystic
      lesion centrally in the liver. The resection specimen revealed a hepatobiliary
      cystadenocarcinoma. HBC and cystadenocarcinoma may give rise to obstructive
      jaundice. Evaluation with cross-sectional imaging techniques is useful. ERCP is a
      useful tool to differentiate extraductal from intraductal obstruction.

PMID- 17007034
TI  - Benign multicystic peritoneal mesothelioma: a case report and review of the
      literature.
AB  - Benign multicystic peritoneal mesothelioma (BMPM) is a rare tumor that occurs
      mainly in women in their reproductive age. The pathogenesis of BMPM is unclear
      and a controversy regarding its neoplastic and reactive nature exists. The
      biological behavior of BMPM is characterized by its slowly progressive process
      and high rate of recurrence after surgical resection. In addition this lesion
      does not present a strong tendency to transform into malignancy. Today
      approximately 130 cases have been reported. We here report a 62-year-old woman
      who had diffuse abdominal pain, nausea and vomiting. Physical examination
      revealed a painful mass in her upper abdomen. She reported a mild dehydration,
      but the vital signs were normal. Peristaltic rushes, gurgles and high-pitched
      tinkles were audible. Upright plain abdominal film revealed small bowel loops
      with air-fluid levels. She was diagnosed having an incarcerated incisional hernia
      that resulted in intestinal obstruction. The patient underwent surgery during
      which a cystic mass of the right ovary measuring 6 cm multiply 5 cm multiply 4
      cm, four small cysts of the small bowel (1 cm in diameter) and a cyst at the
      retroperitoneum measuring 11 cm multiply 10 cm multiply 3 cm were found. Complete
      resection of the lesion was performed. The patient had an uneventful recovery and
      had no recurrence two years after surgery.

PMID- 17007035
TI  - Activation of c-Yes in hepatocellular carcinoma: a preliminary study.

PMID- 17007036
TI  - Unilateral leg edema in a cirrhotic patient with tense ascites.

PMID- 17007037
TI  - Diagnostic dilemma between intestinal Behcet disease and inflammatory bowel
      disease with pyoderma gangrenosum.

PMID- 17007039
TI  - Non-surgical treatment of esophageal achalasia.
AB  - Esophageal achalasia is an infrequent motility disorder characterized by a
      progressive stasis and dilation of the oesophagus; with subsequent risk of
      aspiration, weight loss, and malnutrition. Although the treatment of achalasia
      has been traditionally based on a surgical approach, especially with the
      introduction of laparoscopic techniques, there is still some space for a medical
      approach. The present article reviews the non-surgical therapeutic options for
      achalasia.

PMID- 17007038
TI  - Gastric atrophy, diagnosing and staging.
AB  - H. pylori is now accepted as the cause of gastritis and gastritis-associated
      diseases, such as duodenal ulcer, gastric ulcer, gastric carcinoma, and gastric
      MALT lymphoma. The natural history of H. pylori gastritis includes inflammation
      progressing from the antrum into the adjacent corpus resulting in an atrophic
      front of advancing injury leading to a reduction in acid secretion and eventual
      loss of parietal cells and development of atrophy. Sub-typing intestinal
      metaplasia has no clinical value to the patient, the pathologist, or the
      endoscopist. The pattern, extent, and severity of atrophy, with or without
      intestinal metaplasia, is a far more important predictor than is intestinal
      metaplasia subtype. The challenge remains to identify a reliable marker that
      relates to pre-malignant potential.

PMID- 17007040
TI  - Gastric carditis: Is it a histological response to high concentrations of luminal
      nitric oxide?
AB  - During the last decade, inflammation (carditis) and intestinal metaplasia
      localized to immediately below the human gastro-oesophageal junction have
      received much attention in relation to the rising incidence of cancer at this
      site. Since these histological findings are frequently observed even among those
      who are H pylori-negative, the causative factors for such histologic events at
      the human gastro-oesophageal junction remain obscure. A series of recent studies
      have demonstrated that a high level of salivary nitrite is sustained over several
      hours after the ingestion of a high nitrate meal, and that the nitrite in
      swallowed saliva is rapidly converted to nitric oxide by an acid catalyzed
      chemical reaction at the gastro-oesophageal junction. Eventually, a substantial
      amount of nitric oxide diffuses from the lumen into the adjacent tissue.
      Therefore, the human gastro-oesophageal junction is likely to be a region of high
      nitrosative stress. Considering the life-time exposure of the gastro-oesophageal
      junction to cytotoxic levels of nitric oxide, this may account for the high
      prevalence of inflammation, intestinal metaplasia, and subsequent development of
      neoplasia at this site. Although gastric acid, pepsin, and bile acid have been
      intensively investigated as a cause of adenocarcinoma at the gastro-oesophageal
      junction and the distal esophagus, nitric oxide and the related nitrosative
      stress should also be examined.

PMID- 17007041
TI  - Risk factors of gastric cancer specific for tumor location and histology in Cali,
      Colombia.
AB  - AIM: To examine histology- and tumor-location specific risk factors of gastric
      cancer (GC). METHODS: This was a case-control study. The study subjects were 216
      GC patients newly diagnosed during the period 2000-2002 and 431 controls selected
      from non-cancer patients matching in age, gender, and hospital. We obtained
      information on lifestyles, dietary habits, and others by a questionnaire.
      RESULTS: The subjects who were not eldest among his/her siblings were at a
      slightly elevated GC risk (OR 1.3; 95% CI 0.8-2.0). Salting meals before tasting
      was related to an increased GC risk (OR 3.5; 95% CI 1.6- 7.3). Frequent
      consumptions of fruits (OR 0.3; 95% CI 0.1-1.0) and vegetables (OR 0.3; 95% CI
      0.1-1.0) were related to decreased GC risks. On the other hand, frying foods (OR
      1.9; 95% CI 1.0-3.6) and cooking with coal (OR 1.8; 95% CI 1.3-2.6) were related
      to increased GC risks. Neither Laurenos histological classification (intestinal
      and diffuse types) nor tumor location significantly affected those associations
      except birth order. The subjects who were not eldest among his/her siblings had
      an increased risk of GCs in the distal and middle thirds, and their ORs were 1.7
      (95% CI 1.0-2.8) and 1.9 (95% CI 0.8-4.3), respectively. The corresponding OR in
      the upper third stomach was 0.3 (95% CI 0.1-0.9). The differences of those three
      ORs were statistically significant (P = 0.010). CONCLUSION: The present study
      shows that birth order, salt intake, consumption of fruits and vegetables, the
      type of cooking, and cigarette smoking are related to GC risk. In histology and
      tumor-location specific analyses, non-eldest person among their siblings is
      related to an increased GC risk in the distal and middle thirds of the stomach,
      and is related to a decreased GC risk in the cardia.

PMID- 17007042
TI  - Inhibitory effect of arsenic trioxide on angiogenesis and expression of vascular
      endothelial growth factor in gastric cancer.
AB  - AIM: To investigate the inhibitory effect of As(2)O(3) on angiogenesis of tumor
      and expression of vascular endothelial growth factor (VEGF) in tumor cells in
      vivo and in vitro. METHODS: The solid tumor model was formed in nude mice with
      the gastric cancer cell line SGC-7901. The animals were randomly divided into
      three groups. As(2)O(3) was injected into the arsenic-treated groups (2.5 mg/kg
      and 5 mg/kg) and the same volume of saline solution was injected into the control
      group. Microvessel density (MVD) and expression of VEGF were detected with
      immunofluorescence laser confocal technology. Further expression of VEGF protein
      and VEGF mRNA was measured with Western bloting and fluorescence quantitative RT-
      PCR in SGC-7901 cells treated with As(2)O(3). RESULTS: In nude mice, after
      treatment with 5 mg/kg and 2.5 mg/kg As(2)O(3) respectively, about 50% and 30%
      tumor growth inhibition were observed correspondingly (P<0.05, P<0.05). Decrease
      in MVD appeared in As(2)O(3)-treated tumors compared with control group (P<0.001,
      P<0.001). MVD in tumors was significantly lower in 5 mg/kg group than in 2.5
      mg/kg group (P<0.01). The fluorescence intensity levels of VEGF in tumor cells
      were significantly lowered in the arsenic-treated groups (P<0.01, P<0.01). The
      fluorescence intensity level of VEGF in 5 mg/kg group was lower than that in 2.5
      mg/kg group (P<0.01). In vitro, the expression of VEGF protein decreased in dose-
      and time-dependent manner after the treatment with As(2)O(3), but in VEGF mRNA no
      significant difference was found between the control group and the treated
      groups. CONCLUSION: As(2)O(3) can inhibit solid tumor growth by inhibiting the
      formation of new blood vessels. One of the mechanisms is that As(2)O(3) can
      inhibit VEGF protein expression.

PMID- 17007043
TI  - Prevalence of autoantibodies and the risk of autoimmune thyroid disease in
      children with chronic hepatitis C virus infection treated with interferon-alpha.
AB  - AIM: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus
      (HCV)-infected children focusing on thyroid autoimmunity. METHODS: We
      investigated the prevalence of auto-antibodies in 123 chronic HCV-infected
      children before, during and after monotherapy with interferon-alpha (IFN-alpha)
      or combined treatment with interferon-alpha or peginterferon-alpha and ribavirin.
      Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney
      microsomes (LKM), the incidence of anti-thyroid peroxidase antibodies as well as
      thyroid function parameters (TSH, FT3 and FT4) were determined. RESULTS: We found
      that 8% of children had autoantibodies before treatment. During treatment, 18% of
      children were found positive for at least one autoantibody; 15.5% of children
      developed pathologic thyroid values during IFN-alpha treatment compared to only
      one child before therapy. Six children had to be substituted while developing
      laboratory signs of hypothyroidism. CONCLUSION: Our data indicate a strong
      correlation between interferon-alpha treatment and autoimmune phenomena, notably
      the emergence of thyroid antibodies. The fact that some children required hormone
      replacement underlines the need of close monitoring in particularly those who
      respond to therapy and have to be treated for more than 6 mo.

PMID- 17007044
TI  - Human beta-defensin-3 induction in H. pylori-infected gastric mucosal tissues.
AB  - AIM: To examine human beta-defensin-3 (hBD-3) expression in inflamed gastric
      mucosal tissues or MKN45 gastric cancer cells with or without H. pylori infection
      for better understanding the innate immune response to H. pylori. METHODS: We
      used reverse transcription-polymerase chain reactions and immunohistochemistry to
      examine hBD-3 expression in inflamed gastric mucosal tissues or MKN45 gastric
      cancer cells with or without H. pylori. Effects of hBD-3 against H. pylori were
      also evaluated. RESULTS: The mean mRNA expression of hBD-3 in H. pylori-positive
      specimens was significantly higher than that in H pylori-negative specimens (P =
      0.0002, Mann-Whitney). In addition, unlike uninfected samples, 8 of 15 (53.33%)
      infected mucosal samples expressed hBD-3 protein. H. pylori dose-dependently
      induced mRNA expression of hBD-3 in MKN45 cells, an effect inhibited by adding
      anti-toll-like receptor (TLR)-4 antibody. HBD-3 protein completely inhibited H.
      pylori growth. CONCLUSION: Our results suggest that like hBD-2, hBD-3 may be
      involved in the pathophysiology of H. pylori-induced gastritis.

PMID- 17007045
TI  - Bromophenacyl bromide, a phospholipase A2 inhibitor attenuates chemically induced
      gastroduodenal ulcers in rats.
AB  - AIM: To study the effect of bromophenacyl bromide (BPB), a phospholipase A2
      inhibitor on gastric secretion and to protect chemically induced gastric and
      duodenal ulcers in rats. METHODS: Acid secretion studies were undertaken in
      pylorus-ligated rats with BPB treatment (0, 5, 15 and 45 mg/kg). Gastric and
      duodenal lesions in the rats were induced by ethanol and cysteamine respectively.
      The levels of gastric wall mucus, nonprotein sulfhydryls (NP-SH) and
      myeloperoxidase (MPO) were also measured in the glandular stomach of rats
      following ethanol induced gastric lesions. RESULTS: BPB produced a dose-dependent
      inhibition of gastric acid secretion and acidity in rats. Pretreatment with BPB
      significantly attenuated the formation of ethanol induced gastric lesion. BPB
      also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The
      antiulcer activity of BPB was associated with significant inhibition of ethanol
      induced depletion of gastric wall mucus, NP-SH and MPO. These findings pointed
      towards the mediation of sulfhydryls in BPB induced gastrointestinal
      cytoprotection. CONCLUSION: BPB possesses significant antiulcer and
      cytoprotective activity against experimentally induced gastroduodenal lesions.

PMID- 17007046
TI  - Effect of intestinal lymphatic circulation blockage in two-hit rats.
AB  - AIM: To study the effect of blocking intestinal lymphatic circulation in two-hit
      rats and explore the significance of intestinal lymphatic circulation in two-hit.
      METHODS: Wistar rats were divided equally into three groups: mesenteric lymph
      duct ligation group, non-ligation group and sham group. Mesenteric lymph was
      diverted by ligation of mesenteric lymph duct, and the two-hit model was
      established by hemorrhage and lipopolysaccharide (LPS) methods. All rats were
      sampled for serum pre-experiment and 24 h post-experiment. The organs including
      kidney, liver, lung and heart were collected for pathomorphologic observation and
      biochemical investigation. The nitric oxide (NO), malondialdehyde (MDA) and
      superoxide dismutase (SOD) were determined in serum and tissue homogenate.
      RESULTS: Pathomorphology study showed that the structures of kidney, lung, liver
      and heart tissues were normal in sham group; congestion, degeneration and
      necrosis in non-ligation group; but only mild lesions in ligation group. After
      two-hits, the contents of AST, ALT, BUN, Cr and LDH-1 in the serum of non
      ligation group and ligation group were obviously higher than that in pre
      experiment group and sham group, but obviously lower than that in non-ligation
      group. The contents of NO(2)(-)/NO(3)(-), NOS, iNOS and MDA in the serum of non
      ligation group were significantly increased, compared with pre-experiment and
      sham group, but SOD was significantly lower. These parameters were significantly
      different in ligation group compared with that in sham group, but NO2-/NO3-, iNOS
      and MDA in ligation group were significantly lower than that in non-ligation
      group. CONCLUSION: Ligation of mesenteric lymph duct could improve the
      disturbance of organic function and morphologic damage in two-hit rats; the
      lymphatic mechanism in two-hit should be emphasized.

PMID- 17007047
TI  - Effect of nutritional counselling on hepatic, muscle and adipose tissue fat
      content and distribution in non-alcoholic fatty liver disease.
AB  - AIM: To assess the effectiveness of the current UK clinical practice in reducing
      hepatic fat (IHCL). METHODS: Whole body MRI and (1)H MRS were obtained, before
      and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles
      in 10 subjects with non-alcoholic fatty liver disease (NAFLD). RESULTS: A 500
      Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,)
      accompanied by significant reductions in most adipose tissue (AT) depots,
      including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra
      abdominal-AT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced
      in the tibialis muscle (-28.2%). Decreases in both IHCL (-39.9%) and soleus IMCL
      (-12.2%) content were also observed, although these were not significant. Several
      individuals showed dramatic decreases in IHCL, while others paradoxically showed
      increases in IHCL content. Changes in body composition were accompanied by
      improvements in certain liver function tests: serum aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT). Significant correlations were found
      between decreases in IHCL and reductions in both intra-abdominal and abdominal
      subcutaneous AT. Improvements in liver function tests were associated with
      reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION: This
      study shows that even a very modest reduction in body weight achieved through
      lifestyle modification can result in changes in body fat depots and improvements
      in LFTs.

PMID- 17007048
TI  - Adult-to-adult right lobe living donor liver transplantation: comparison of
      endoscopic retrograde cholangiography with standard T2-weighted magnetic
      resonance cholangiography for evaluation of donor biliary anatomy.
AB  - AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and
      standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation
      process as adult-to-adult right lobe living donor liver transplantation (LDLTx)
      demands a successful outcome, and exact knowledge of the biliary tree is
      implicated to avoid biliary complications, postoperatively. METHODS: After
      starting the LDLTx program, 18 liver transplant candidates were selected for
      LDLTx by a stepwise evaluation process. ERC and standard T2-weighted MRC were
      performed to evaluate the biliary system of the donor liver. The anatomical
      findings of ERC and MRC mapping were compared using the Ohkubo classification.
      RESULTS: ERC allowed mapping of the whole biliary system in 15/15 (100%) cases,
      including 14/15 (93.3%) with biliary variants while routine MRC was only accurate
      in 2/13 (15.4%) cases. MRC was limited in depicting the biliary system proximal
      of the hepatic bifurcation. Postoperative biliary complications occurred in 2
      donors and 8 recipients. Biliary complications were associated with Ohkubo type
      C, E or G in 6/8 recipients, and 2/3 recipients with biliary leak received a
      graft with multiple (>=2) bile ducts. CONCLUSION: Pretransplant ERC is safe and
      superior over standard MRC for detection of biliary variations that occur with a
      high frequency. However, precise knowledge of biliary variants did not reduce the
      incidence of postoperative biliary complications.

PMID- 17007049
TI  - Fatty liver, carotid disease and gallstones: a study of age-related associations.
AB  - AIM: To evaluate carotid intima-media thickening (IMT) and plaques, gallstone
      disease (GD) and fatty liver (FL) as a function of age. METHODS: In 449 subjects,
      FL and carotid disease were assessed ultrasonographically. In a subgroup of
      65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease,
      GD and associated factors were determined. RESULTS: FL of unspecified etiology
      was more common in younger and GD in older individuals. FL subjects had an
      increased prevalence of IMT and a decreased prevalence of plaques and manifested
      carotid disease earlier. Plaques were more common in subjects with GD. Age was an
      independent predictor of carotid disease outcome and FL was a protective factor
      for plaques. In NAFLD, there was an inverse correlation between body weight and
      age and the latter independently predicted carotid findings. CONCLUSION:
      Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a
      function of age and body weight.

PMID- 17007050
TI  - Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue
      in comparison with bone marrow mesenchymal stem cells.
AB  - AIM: To investigate and compare the hepatogenic transdifferentiation of adipose
      tissue-derived stem cells (ADSC) and bone marrow-derived mesenchymal stem cells
      (BMSC) in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been
      described. Adipose tissue represents an accessible source of ADSC, with similar
      characteristics to BMSC. METHODS: BMSCs were obtained from patients undergoing
      total hip arthroplasty and ADSC from human adipose tissue obtained from
      lipectomy. Cells were grown in medium containing 15% human serum. Cultures were
      serum deprived for 2 d before cultivating under similar pro-hepatogenic
      conditions to those of liver development using a 2-step protocol with sequential
      addition of growth factors, cytokines and hormones. Hepatic differentiation was
      RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.
      RESULTS: BMSC and ADSC exhibited a fibroblastic morphology that changed to a
      polygonal shape when cells differentiated. Expression of stem cell marker Thy1
      decreased in differentiated ADSC and BMSC. However, the expression of the hepatic
      markers, albumin and CYPs increased to a similar extent in differentiated BMSC
      and ADSC. Hepatic gene activation could be attributed to increased liver-enriched
      transcription factors (C/EBPbeta and HNF4alpha), as demonstrated by adenoviral
      expression vectors. CONCLUSION: Mesenchymal stem cells can be induced to
      hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic
      differentiation potential to BMSC, but a longer culture period and higher
      proliferation capacity. Therefore, adipose tissue may be an ideal source of large
      amounts of autologous stem cells, and may become an alternative for hepatocyte
      regeneration, liver cell transplantation or preclinical drug testing.

PMID- 17007052
TI  - Doppler study of hepatic vein in cirrhotic patients: correlation with liver
      dysfunction and hepatic hemodynamics.
AB  - AIM: To elucidate the significance of Doppler measurements of hepatic vein in
      cirrhotic patients and to correlate with liver dysfunction and hepatic
      hemodynamics. METHODS: One hundred patients with liver cirrhosis and 60 non
      cirrhotic controls were studied. Doppler waveforms were obtained from right
      hepatic vein and flow velocity measured during quiet respiration. Doppler
      measurements were also obtained from portal trunk, right portal vein and proper
      hepatic artery. RESULTS: Hepatic vein waveforms were classified into three
      classical patterns. Flat waveform was uncommon. Mean hepatic vein velocity was
      significantly higher in cirrhotic patients (12.7 +/- 6.4 vs 5.1 +/- 2.1 and 6.2
      +/- 3.2 cm/s; P<0.0001). The poorer the grade of cirrhosis, the higher was the
      mean velocity. Maximum forward velocity was never greater than 40 cm/s in
      controls. Degree of ascites was found to be highly correlated with mean velocity.
      "Very highq group (>=20 cm/s) presented clinically with moderate to massive
      ascites. Correlations between right portal flow and mean velocity was significant
      (P<0.0001, r = 0.687). CONCLUSION: Doppler waveforms of hepatic vein, which is
      independent of liver dysfunction, should be obtained during normal respiration.
      Mean hepatic vein velocity reflects the change in hepatic circulation associated
      with progression of liver cirrhosis. It can be used as a new parameter in the
      assessment of liver cirrhosis.

PMID- 17007051
TI  - Improved method of plasma 8-Isoprostane measurement and association analyses with
      habitual drinking and smoking.
AB  - AIM: To develop a simple and accurate method for quantifying 8-isoprostane in
      plasma by employing a combination of two-step solid-phase extraction of samples
      and a commercially available ELISA kit, and by this method to examine the effects
      of drinking and smoking habits against the levels of plasma 8-isoprostane in
      healthy Japanese volunteers. METHODS: Plasma 8-isoprostane was extracted with ODS
      gel suspension followed by NH(2) Sep-Pak column. The 8-isoprostane fractions were
      assayed using a commercially available ELISA kit. We measured plasma 8
      isoprostane levels in 157 healthy Japanese volunteers divided into three groups
      (64 non-habitual drinkers, 56 moderate drinkers and 37 habitual drinkers)
      according to their alcohol consumption per week. Genotypes of aldehyde
      dehydrogenase 2 (ALDH2) were also determined to investigate the plasma 8
      isoprostane levels with reference to drinking habits. In addition, the plasma 8
      isoprostane levels of 96 non-smokers and 61 smokers from the same subjects were
      compared. RESULTS: Our method fulfilled all the requirements for use in routine
      clinical assays with respect to sensitivity, intra- and inter-assay
      reproducibility, accuracy and dynamic assay range. Significant increases of
      plasma 8-isoprostane levels were observed in female habitual drinkers when
      compared with those of non-habitual drinkers (t = 5.494, P<0.0001) as well as
      moderate drinkers (t = 3.542, P<0.005), and 8-isoprostane levels were also
      significantly different between ALDH2*2/1 and ALDH2*1/1 in the female habitual
      drinkers (t = 6.930, P<0.0001), suggesting that excessive drinking of alcohol may
      increase oxidization stress, especially in females. On the contrary, no
      significant difference of the plasma 8-isoprostane levels was observed between
      non-smokers and smokers. CONCLUSION: Our present method was proved to be a simple
      and accurate tool for measuring plasma 8-isoprostane. However, the clinical
      utility of plasma 8-isoprostane for drinking and smoking habits was limited since
      elevated 8-isoprostane levels were observed in female heavy drinkers, and no
      association was found between smokers and nonsmokers.

PMID- 17007053
TI  - Acute interstitial edematous pancreatitis: Findings on non-enhanced MR imaging.
AB  - AIM: To study the appearances of acute interstitial edematous pancreatitis (IEP)
      on non-enhanced MR imaging. METHODS: A total of 53 patients with IEP diagnosed by
      clinical features and laboratory findings were underwent MR imaging. MR imaging
      sequences included fast spoiled gradient echo (FSPGR) fat saturation axial T1
      weighted imaging, gradient echo T1-weighted (in phase), single shot fast spin
      echo (SSFSE) T2-weighted, respiratory triggered (R-T) T2-weighted with fat
      saturation, and MR cholangiopancreatography. Using the MR severity score index,
      pancreatitis was graded as mild (0-2 points), moderate (3-6 points) and severe (7
      10 points). RESULTS: Among the 53 patients, IEP was graded as mild in 37 patients
      and as moderate in 16 patients. Forty-seven of 53 (89%) patients had at least one
      abnormality on MR images. Pancreas was hypointense relative to liver on FSPGR T1
      weighted images in 18.9% of patients, and hyperintense in 25% and 30% on SSFSE T2
      weighted and R-T T2-weighted images, respectively. The prevalences of the
      findings of IEP on R-T T2-weighted images were, respectively, 85% for pancreatic
      fascial plane, 77% for left renal fascial plane, 55% for peripancreatic fat
      stranding, 42% for right renal fascial plane, 45% for perivascular fluid, 40% for
      thickened pancreatic lobular septum and 25% for peripancreatic fluid, which were
      markedly higher than those on in-phase or SSFSE T2-weighted images (P<0.001).
      CONCLUSION: IEP primarily manifests on non-enhanced MR images as thickened
      pancreatic fascial plane, left renal fascial plane, peripancreatic fat stranding,
      and peripancreatic fluid. R-T T2-weighted imaging is more sensitive than in-phase
      and SSFSE T2-weighted imaging for depicting IEP.

PMID- 17007054
TI  - The epidemiology of hyperferritinaemia.
AB  - AIM: To discover the causes of markedly raised ferritin levels in patients seen
      at a teaching hospital in Newcastle Upon Tyne, United Kingdom. METHODS:
      Demographic and medical data were collected for all patients over 18 years who
      had a serum ferritin levels recorded as >=1500 microg/L during the period January
      to September 2002. The cause or causes for their hyperferritinaemia were
      identified from their medical notes. Patients from a defined local population
      were identified. RESULTS: A total of 19583 measurements were provided of which
      406 from 199 patients were >=1500 microg/L. An annual incidence for the local
      population was determined to be 0.44/1000. 150/199 medical notes were scrutinised
      and 81 patients were identified as having a single cause for their raised
      ferritin level. The most common single cause was alcoholic liver disease in the
      local population and renal failure was the most common single cause in the
      overall population. Confirmed hereditary haemochromatosis was the 10th most
      common cause. Liver disease contributed to hyperferritinaemia in 44% of the
      patients. Weight loss may have contributed to hyperferritinaemia in up to 11%.
      CONCLUSION: Alcohol related liver disease, haemat-ological disease, renal failure
      and neoplasia are much more common causes of marked hyperferritinaemia than
      haemochromatosis. The role of weight loss in hyperferritinaemia may warrant
      further investigation.

PMID- 17007055
TI  - Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases.
AB  - AIM: To investigate the expression of nucleoporin 88 (Nup88) in hepatitis B virus
      (HBV) and C virus (HCV)-related liver diseases. METHODS: We generated a new
      monoclonal Nup88 antibody to investigate the Nup88 protein expression by
      immunohistochemistry (IHC) in 294 paraffin-embedded liver specimens comprising
      all stages of hepatocellular carcinogenesis. In addition, in cell culture
      experiments HBV-positive (HepG2.2.15 and HB611) and HBV-negative (HepG2) hepatoma
      cell lines were tested for the Nup88 expression by Western-immunoblotting to test
      data obtained by IHC. RESULTS: Specific Nup88 expression was found in chronic HCV
      hepatitis and unspecific chronic hepatitis, whereas no or very weak Nup88
      expression was detected in normal liver. The Nup88 expression was markedly
      reduced or missing in mild chronic HBV infection and inversely correlated with
      HBcAg expression. Irrespective of the HBV- or HCV-status, increasing Nup88
      expression was observed in cirrhosis and dysplastic nodules, and Nup88 was highly
      expressed in hepatocellular carcinomas. The intensity of Nup88 expression
      significantly increased during carcinogenesis (P<0.0001) and correlated with
      dedifferentiation (P<0.0001). Interestingly, Nup88 protein expression was
      significantly downregulated in HBV-positive HepG2.2.15 (P<0.002) and HB611
      (P<0.001) cell lines as compared to HBV-negative HepG2 cells. CONCLUSION: Based
      on our immunohistochemical data, HBV and HCV are unlikely to influence the
      expression of Nup88 in cirrhotic and neoplastic liver tissue, but point to an
      interaction of HBV with the nuclear pore in chronic hepatitis. The expression of
      Nup88 in nonneoplastic liver tissue might reflect enhanced metabolic activity of
      the liver tissue. Our data strongly indicate a dichotomous role for Nup88 in non
      neoplastic and neoplastic conditions of the liver.

PMID- 17007056
TI  - Elevated plasma levels of N-terminal pro-brain natriuretic peptide in patients
      with chronic hepatitis C during interferon-based antiviral therapy.
AB  - AIM: To investigate plasma levels of N-terminal pro-brain natriuretic peptide (NT
      proBNP), an established marker of cardiac function, in patients with chronic
      hepatitis C during interferon-based antiviral therapy. METHODS: Using a sandwich
      immunoassay, plasma levels of NT-proBNP were determined in 48 patients with
      chronic hepatitis C at baseline, wk 24 and 48 during antiviral therapy and at wk
      72 during follow-up. RESULTS: Plasma NT-proBNP concentrations were significantly
      increased (P<0.05) at wk 24, 48 and 72 compared to the baseline values. NT-proBNP
      concentrations at baseline and wk 24 were closely correlated (r = 0.8; P<0.001).
      At wk 24, 7 (14.6%) patients had NT-proBNP concentrations above 200 ng/L compared
      to 1 (2%) patient at baseline (P = 0.059). Six of these 7 patients had been
      treated with high-dose IFN-alpha induction therapy. In multiple regression
      analysis, NT-proBNP was not related to other clinical parameters, biochemical
      parameters of liver disease or virus load and response to therapy. CONCLUSION:
      Elevated levels of NT-proBNP during and after interferon-based antiviral therapy
      of chronic hepatitis C may indicate the presence of cardiac dysfunction, which
      may contribute to the clinical symptoms observed in patients during therapy.
      Plasma levels of NT-proBNP may be used as a diagnostic tool and for guiding
      therapy in patients during interferon-based antiviral therapy.

PMID- 17007057
TI  - Sustained low diffusing capacity in hepatopulmonary syndrome after liver
      transplantation.
AB  - AIM: To study the presence of sustained low diffusing capacity (DL(CO)) after
      liver transplantation (LT) in patients with hepatopulmonary syndrome (HPS).
      METHODS: Six patients with mild-to-severe HPS and 24 without HPS who underwent LT
      were prospectively followed before and after LT at mid-term (median, 15 mo). HPS
      patients were also assessed at long-tem (median, 86 mo). RESULTS: Before LT, HPS
      patients showed lower PaO(2) (71 +/- 8 mmHg), higher AaPO(2) (43 +/- 10 mmHg) and
      lower DL(CO) (54% +/- 9% predicted), due to a combination of moderate-to-severe
      ventilation-perfusion (V(A)/Q) imbalance, mild shunt and diffusion limitation,
      than non-HPS patients (94 +/- 4 mmHg and 19 +/- 3 mmHg, and 85% +/- 3% predicted,
      respectively) (P<0.05 each). Seven non-HPS patients had also reduced DL(CO) (70%
      +/- 4% predicted). At mid- and long-term after LT, compared to pre-LT, HPS
      patients normalized PaO(2) (91 +/- 3 mmHg and 87 +/- 5 mmHg), AaPO(2) (14 +/- 3
      mmHg and 23 +/- 5 mmHg) and all V(A)/Q descriptors (P<0.05 each) without changes
      in DL(CO) (53% +/- 8% and 56% +/- 7% predicted, respectively). Post-LT DL(CO) in
      non-HPS patients with pre-LT low DL(CO) was unchanged (75% +/- 6% predicted).
      CONCLUSION: While complete V(A)/Q resolution in HPS indicates a reversible
      functional disturbance, sustained low DL(CO) after LT also present in some non
      HPS patients, points to persistence of sub-clinical liver-induced pulmonary
      vascular changes.

PMID- 17007058
TI  - ECA39 is a novel distant metastasis-related biomarker in colorectal cancer.
AB  - AIM: To investigate the possible role of polysaccharide-K (PSK) -related markers
      in predicting distant metastasis and in the clinical outcome of colorectal cancer
      (CRC). METHODS: Firstly, we used protein microarrays to analyze the in vitro
      expression profiles of potential PSK-related markers in the human colorectal
      adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we
      investigated the clinical implications of these markers in the prognosis of CRC
      patients. RESULTS: ECA39, a direct target of c-Myc, was identified as a candidate
      protein affected by the anti-metastatic effects of PSK. Immunohistochemistry
      revealed that ECA39 was expressed at significantly higher levels in tumor tissues
      with distant metastases compared to those without (P<0.00001). Positive ECA39
      expression was shown to be highly reliable for the prediction of distant
      metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value:
      86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr
      disease free survival rate was observed in the ECA39-negative patient group
      (77.3%) compared with the ECA39-positive patient group (25.8%) (P<0.05).
      CONCLUSION: Our results suggest that ECA39 is a dominant predictive factor for
      distant metastasis in patients with advanced CRC and that its suppression by PSK
      might represent a useful application of immunotherapy as part of a program of
      integrated medicine.

PMID- 17007059
TI  - Organisms causing spontaneous bacterial peritonitis in children with liver
      disease and ascites in Southern Iran.
AB  - AIM: To determine the causative agents of spontaneous bacterial peritonitis (SBP)
      in children with liver disease and ascites in our center. METHODS: During a 2.5
      year period, from September 2003 to March 2006, 12 patients with 13 episodes of
      SBP were studied. In all cases at the time of admission serum albumin and
      glucose, urinalysis and urine culture was performed. Analysis [white blood cell
      (WBC) count with differential, albumin, glucose], gram stain, culture by BACTEC
      method and antibiogram was done on ascitic fluids. Abdominal paracentesis was
      repeated after 48 h of antibiotic therapy for bacteriologic assay. The patients
      were followed for at least three months in a gastroenterology clinic. RESULTS:
      There were 7 girls (58%) and 5 boys (42%) with a median age of 5.2 years (range,
      6 mo to 16 years). All cases had positive ascitic fluid culture. Gram stain was
      positive in 5 (38.5%) of them. The isolated organisms were S. pneumoniae in 5
      (38.5%), E. coli in 2 (15.3%), S. viridans in 2 (15.3%), and K. pneumoniae, H.
      influenza, Enterococci, and nontypable Streptococcus each in one (7.7%). All of
      them except Enterococci were sensitive to ciprofloxacin and ceftriaxone. All
      ascitic fluid cultures were negative after 48 h of antibiotic therapy.
      CONCLUSION: S. pneumoniae is the most common cause of SBP in the pediatric age
      group and we recommend a third generation cephalosporine (e.g., Ceftriaxione or
      Cefotaxime) for empirical therapy in children with SBP.

PMID- 17007060
TI  - Comparison of different diagnostic methods in infants with Cholestasis.
AB  - AIM: To evaluate different methods in differentiating idiopathic neonatal
      hepatitis from biliary atresia. METHODS: Sixty-five infants with cholestatic
      jaundice and final diagnosis of idiopathic neonatal hepatitis and biliary atresia
      were studied prospectively from September 2003 to March 2006. A thorough history
      and physical examination were undertaken and the liver enzymes were examined. All
      cases underwent abdominal ultrasonography, hepatobiliary scintigraphy, and
      percutaneous liver biopsy. The accuracy, sensitivity, specificity and predictive
      values of these various methods were compared. RESULTS: There were 34 girls and
      31 boys, among them 46 subjects had idiopathic neonatal hepatitis (age, 61 +/- 17
      d) and 19 had biliary atresia (age, 64 +/- 18 d). The mean age at onset of
      jaundice was significantly lower in cases of biliary atresia when compared to
      idiopathic neonatal hepatitis cases (9 +/- 13 d vs 20 +/- 21 d; P = 0.032). The
      diagnostic accuracy of different methods was as follows: liver biopsy, 96.9%;
      clinical evaluation, 70.8%; ultrasonography, 69.2%; hepatobiliary scintigraphy,
      58.5%; and liver enzymes, 50.8%. CONCLUSION: Our results indicate that clinical
      evaluation by an experienced pediatric hepatologist and a biopsy of the liver are
      considered as the most reliable methods to differentiate idiopathic neonatal
      hepatitis and biliary atresia.

PMID- 17007062
TI  - Endoscopic placement of flatus tube using "lasso" technique with snare wire.
AB  - A 55-year old man presented with acute sigmoid volvulus. The distal level of
      obstruction was above the level which could be reached by the rigid sigmoidoscope
      to allow decompression, and so a flatus tube was "lassoed" onto the side of a
      flexible endoscope which allowed accurate placement under direct vision. This
      technique allows accurate placement of catheters, feeding tubes and other devices
      endoscopically, which cannot be placed through the instrument channel of the
      endoscope.

PMID- 17007061
TI  - Effect of electroacupuncture at Sibai on the gastric myoelectric activities of
      denervated rats.
AB  - AIM: To explore the mechanism of the exciting effects of electro-acupuncture (EA)
      at Sibai on the gastric myoelectric activities. METHODS: A total of 32 rats were
      randomly divided into four groups. Through intraperitoneal injection with
      atropine (the anti-cholinergic agent by blockade of muscarinic receptors),
      hexamethonium (automatic nerve ganglion-blocking agent) and reserpine (anti
      adrenergic agent by depleting the adrenergic nerve terminal of its norepinephrine
      store), effects of EA at Sibai on the gastric myoelectric activities of the
      denervated rats were observed. RESULTS: After intraperitoneal injection of
      atropine and hexamethonium, the average amplitude and ratio of period to time in
      the phase of high activity of gastric myoelectric slow wave, and the average
      numbers of the peaks of gastric myoelectric fast wave were significantly
      decreased (P<0.01, P<0.05, P<0.01), while after intraperitoneal injection of
      reserpine, the aforementioned three parameters were increased (P<0.01, P<0.05,
      P<0.01). EA at Sibai point partially relieved the inhibitory effect of atropine
      and hexamethonium on the gastric myoelectric activities in the rats (P<0.05 or
      P>0.05). CONCLUSION: Cholinergic and adrenergic nervous systems and autonomic
      nerve ganglion participate in the peripheral passage of the controlling effects
      of EA at Foot Yangming Channel on gastrointestinal tract.

PMID- 17007063
TI  - Autoimmune pancreatitis associated with a large pancreatic pseudocyst.
AB  - Pancreatic cystic lesions comprise various entities with different
      histopathological characteristics and their differential diagnosis is often a
      challenge for clinicians. Autoimmune pancreatitis (AIP) is usually not considered
      in the differential diagnosis of cystic lesions, but often mimics the
      morphological aspects of pancreatic neoplasm. We report the case of a 64-year-old
      male patient with a cystic pancreatic head lesion (diameter 5 cm) and stenosis of
      the distal bile duct requiring repeated stenting. Because of the clinical
      presentation together with moderate elevation of serum CA19-9 and massive
      elevation of cyst fluid CA19-9 (122.695 U/L; normal range: <37.0 U/L), the
      patient underwent explorative laparotomy and pylorus preserving partial
      pancreaticoduodenectomy. Histology revealed surprisingly AIP with an inflammatory
      pseudocyst. In conclusion, cyst fluid analysis of tumor markers and cyst fluid
      cytology lack high accuracy to clearly differentiate cystic pancreatic lesions.
      Although AIP is rarely associated with pseudocysts, the disease has to be
      considered in the differential diagnosis of cystic pancreatic lesions. Early
      examination of serum IgG, IgG4 and auto-antibodies might save these patients from
      unnecessary endoscopical and surgical procedures.

PMID- 17007064
TI  - Is acute dyspnea related to oxaliplatin administration?
AB  - The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin.
      Oxaliplatin improves the efficacy of this combination in patients with stage III
      colon cancer and moreover its toxicity is well tolerable. We describe a rare
      clinical case of acute dyspnoea probably related to oxaliplatin at one month from
      the end of the adjuvant treatment. A 74-year-old man developed a locally advanced
      sigmoid carcinoma (pT3N1M0). A port a cath attached to an open-ended catheter was
      implanted in order to administer primary chemotherapy safely according to the
      FOLFOX4 schedule. One month following the end of the 6th cycle, the patient
      referred a persistent cough and moderate dyspnoea. Chest radiography displayed a
      change in the lung interstitium, chest CT scan confirmed this aspect of adult
      respiratory distress syndrome, spirometry reported a decreased carbon monoxide
      diffusion capacity. Antibiotic and corticosteroids were administered for 10 d,
      then a repeated chest X ray evidenced a progressive pulmonary infiltration. A
      transbronchial biopsy and cytology did not show an infective process, a CT scan
      reported radiological abnormalities including linear and nodular densities which
      were becoming confluents. Antimicotic and antiviral drugs did not evidence any
      benefit. The antiviral therapy was stopped and high dose metilprednisolone was
      started. The patient died of pulmonary distress after 10 d.

PMID- 17007066
TI  - Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis.
AB  - We experienced a very rare case of ulcerative colitis (UC) accompanied with
      analogous lesions in the stomach, duodenum, and ileal J-pouch. Ileal J-pouch anal
      anastomosis was performed on a 29-year old woman in 1996. Six years later, she
      was admitted again to our hospital because of epigastralgia, nausea, watery
      diarrhea and low fever. Based on the results of endoscopic examination, we
      diagnosed it as pouchitis. Moreover, on hypotonic duodenography, expansion of the
      duodenal bulb and the descending portion were poor. Kerckring folds disappeared
      with typical lead-pipe appearance. The pathogenesis of the gastric and duodenal
      lesion in this patient was similar to that of the colonic lesions of UC. For the
      gastroduodenal lesions in this patient, symptomatic remission was obtained
      following administration of crushed mesalazine tablets (1500 mg/d) for 14 d with
      continuous administration of omeprazole. Firstly we used ciprofloxacin to treat
      pouchitis. On the fifth day, she got a fever because of catheter infection. In
      the catheter culture, methicillin-resistant Staphylococcus aureus (MRSA) was
      detected. Therefore we changed ciprofloxacin to vancomycin hydrochloride
      (Vancomycin). Vancomycin was very effective, and the stool frequency dramatically
      improved in three days. Now she continues to take mesalazine, but her condition
      is stable and there has been no recurrence of pouchitis.

PMID- 17007065
TI  - Removal of press-through-packs impacted in the upper esophagus using an overtube.
AB  - Foreign bodies in the upper esophagus should be removed as soon as possible to
      avoid serious complications. However, removals of foreign bodies in the upper
      esophagus are very difficult, especially if they have sharp edges, such as press
      through-packs (PTPs). We experienced four cases of the impacted PTPs in the upper
      esophagus which was successfully extracted endoscopically with the overtube.
      Because two edges of PTPs were so firmly impacted in the esophageal wall in all
      cases, the PTPs were not movable in the upper esophagus. However, after insertion
      of the overtube, PTPs became movable and were successfully extracted and no
      serious complications occurred after extraction of PTPs. In one case, insertion
      of the overtube rapidly expanded the upper esophagus and PTP progressed to the
      gastric cavity and it could be extracted with the endoscopic protector hood. The
      endoscopic removal with the overtube was a simple, safe and effective technique
      for the removal of the impacted PTPs in upper esophagus.

PMID- 17007067
TI  - Translation regulation of intron-containing genes in chloroplasts.
AB  - The paper provides a short description of the originally developed algorithm for
      searching of the conservative protein-RNA binding sites. The algorithm is applied
      to analyze chloroplast genes. The candidate protein-RNA binding sites were
      detected upstream of atpF, petB, clpP, psaA, psbA, and psbB genes in many
      chloroplasts of algae and plants. We suggest that some of these sites are
      involved in suppressing translation until splicing is completed.

PMID- 17007068
TI  - Residue conservation information for generating near-native structures in protein
      protein docking.
AB  - MOTIVATION: Protein-protein docking algorithms typically generate large numbers
      of possible complex structures with only a few of them resembling the native
      structure. Recently (Duan et al., Protein Sci, 14:316-218, 2005), it was observed
      that the surface density of conserved residue positions is high at the interface
      regions of interacting protein surfaces, except for antibody-antigen complexes,
      where a lesser number of conserved positions than average is observed at the
      interface regions. Using this observation, we identified putative interacting
      regions on the surface of interacting partners and significantly improved docking
      results by assigning top ranks to near-native complex structures. In this paper,
      we combine the residue conservation information with a widely used shape
      complementarity algorithm to generate candidate complex structures with a higher
      percentage of near-native structures (hits). What is new in this work is that the
      conservation information is used early in the generation stage and not only in
      the ranking stage of the docking algorithm. This results in a significantly
      larger number of generated hits and an improved predictive ability in identifying
      the native structure of protein-protein complexes. RESULTS: We report on results
      from 48 well-characterized protein complexes, which have enough residue
      conservation information from the same 59 benchmark complexes used in our
      previous work. We compute conservation indices of residue positions on the
      surfaces of interacting proteins using available homologous sequences from
      UNIPROT and calculate the solvent accessible surface area. We combine this
      information with shape-complementarity scores to generate candidate protein
      protein complex structures. When compared with pure shape-complementarity
      algorithms, performed by FTDock, our method results in significantly more hits,
      with the improvement being over 100% in many instances. We demonstrate that
      residue conservation information is useful not only in refinement and scoring of
      docking solutions, but also helpful in enrichment of near-native-structures
      during the generation of candidate geometries of complex structures.

PMID- 17007069
TI  - Reconstructing an ultrametric galled phylogenetic network from a distance matrix.
AB  - Given a distance matrix M that specifies the pairwise evolutionary distances
      between n species, the phylogenetic tree reconstruction problem asks for an edge
      weighted phylogenetic tree that satisfies M, if one exists. We study some
      extensions of this problem to rooted phylogenetic networks. Our main result is an
      O(n(2) log n)-time algorithm for determining whether there is an ultrametric
      galled network that satisfies M, and if so, constructing one. In fact, if such an
      ultrametric galled network exists, our algorithm is guaranteed to construct one
      containing the minimum possible number of nodes with more than one parent (hybrid
      nodes). We also prove that finding a largest possible submatrix M' of M such that
      there exists an ultrametric galled network that satisfies M' is NP-hard.
      Furthermore, we show that given an incomplete distance matrix (i.e. where some
      matrix entries are missing), it is also NP-hard to determine whether there exists
      an ultrametric galled network which satisfies it.

PMID- 17007070
TI  - Clustering biological annotations and gene expression data to identify putatively
      co-regulated biological processes.
AB  - MOTIVATION: Functional profiling is a key step of microarray gene expression data
      analysis. Identifying co-regulated biological processes could help for better
      understanding of underlying biological interactions within the studied biological
      frame. RESULTS: We present herein an original approach designed to search for
      putatively co-regulated biological processes sharing a significant number of co
      expressed genes. An R language implementation named "FunCluster" was built and
      tested on two gene expression data sets. A discriminatory functional analysis of
      the first data set, related to experiments performed on separated adipocytes and
      stroma vascular fraction cells of human white adipose tissue, highlighted the
      prevalent role of nonadipose cells in the synthesis of inflammatory and immunity
      molecules in human adiposity. On the second data set, resulting from a model
      investigating insulin coordinated regulation of gene expression in human skeletal
      muscle, FunCluster analysis spotlighted novel functional classes of putatively co
      regulated biological processes related to protein metabolism and the regulation
      of muscular contraction. AVAILABILITY: Supplementary information about the
      FunCluster tool is available on-line at
      http://corneliu.henegar.info/FunCluster.htm.

PMID- 17007071
TI  - Coexpressionfinder: a new algorithm for finding groups of coexpressed genes.
AB  - RESULTS: A new algorithm is developed which is intended to find groups of genes
      whose expression values change in a concordant manner in a series of experiments
      with DNA arrays. This algorithm is named as CoexpressionFinder. It can find more
      complete and internally coordinated groups of gene expression vectors than
      hierarchical clustering. Also, it finds more genes having coordinated expression.
      The algorithm's design allows parallel execution. AVAILABILITY: The algorithm is
      implemented as a Java application which is freely available at:
      http://www.bioinformatics.ru/cf/index.jsp and
      http://bioinformatics.ru/cf/index.jsp.

PMID- 17007072
TI  - Mathematical modeling of living cell metabolism using the method of steady-state
      stoichiometric flux balance.
AB  - This approach uses a set of algebraic linear equations for reaction rates (the
      method of steady-state stoichiometric flux balance) to model the purposeful
      metabolism of the living self-reproducing biochemical system (i.e. cell), which
      persists in steady-state growth. Linear programming (SIMPLEX method) is used to
      derive the solution for the model equations set (determining reaction rates which
      provide flux balance at given conditions). Here, we demonstrate the approach
      through the mathematical modeling of steady-state metabolism in Saccharomyces
      cerevisiae mitochondria.

PMID- 17007073
TI  - Optimal spectral coordination of subantennae in natural antennae as an efficient
      strategy for light harvesting in photosynthesis.
AB  - This work continues a series of our investigations on efficient strategies of
      functioning of natural light-harvesting antennae, initiated by a concept of
      rigorous optimization of photosynthetic apparatus by functional criterion, and
      deals with the problem of an optimal spectral coordination of subantennae in
      photosynthetic superantenna of the green bacterium Oscillochloris trichoides from
      a new family of green bacteria Oscillochloridaceae based in 2000. At present, two
      subantennae were identified surely: chlorosomal BChl c subantenna B750 and
      membrane BChl a subantennae B805-860. Some indirect experiments indicated on the
      presence of minor amounts of BChl a in isolated chlorosomes which allowed us to
      propose on the existence of an intermediate-energy subantenna which can connect
      the chlorosomal BChl c and the membrane BChl a ones. However, in the absorption
      spectra of isolated chlorosomes, this BChl a subantenna was not visually
      identified. This promoted us to perform a theoretical analysis of the optimality
      of spectral coordination of Oscillochloris trichoides subantennae. Using
      mathematical modeling for the functioning of the natural superantenna, we showed
      that an intermediate-energy subantenna, connecting B750 and B805-860 ones, allows
      one to control superantenna efficiency, i.e. to optimize the excitation energy
      transfer from B750 to B805 by functional criterion, and hence, the existence of
      such intermediate-energy subantenna is biologically expedient.

PMID- 17007074
TI  - A general framework for biclustering gene expression data.
AB  - A large number of biclustering methods have been proposed to detect patterns in
      gene expression data. All these methods try to find some type of biclusters but
      no one can discover all the types of patterns in the data. Furthermore,
      researchers have to design new algorithms in order to find new types of
      biclusters/patterns that interest biologists. In this paper, we propose a novel
      approach for biclustering that, in general, can be used to discover all
      computable patterns in gene expression data. The method is based on the theory of
      Kolmogorov complexity. More precisely, we use Kolmogorov complexity to measure
      the randomness of submatrices as the merit of biclusters because randomness
      naturally consists in a lack of regularity, which is a common property of all
      types of patterns. On the basis of algorithmic probability measure, we develop a
      Markov Chain Monte Carlo algorithm to search for biclusters. Our method can also
      be easily extended to solve the problems of conventional clustering and
      checkerboard type biclustering. The preliminary experiments on simulated as well
      as real data show that our approach is very versatile and promising.

PMID- 17007075
TI  - First seizure: do multiple seizures predict recurrence?

PMID- 17007077
TI  - Abstracts from the 47th International Conference on the Bioscience of Lipids.
      September 5-10, 2006. Pecs, Hungary.

PMID- 17007076
TI  - Objects to veterinarians as animal rights advocates.

PMID- 17007078
TI  - My story: the discovery and mapping to chromosome 21 of the Alzheimer amyloid
      gene.
AB  - When I decided to clone the amyloid gene I did not know that there were some
      twenty groups around the research world that desperately tried to do the same. If
      I knew that I would have never started the project. I was so ignorant about the
      disease that I did not know how to spell the name Alzheimer. I had to look at the
      papers of other researchers to make sure that I my spelling was correct. After
      the cloning, I was invited to numerous national and international meetings on AD.
      These meetings became my University where I majored in AD.

PMID- 17007079
TI  - Immunopotentiators in modern vaccines. Proceedings of the second IMV meeting. May
      18-20, 2005. Malaga, Spain.

PMID- 17007080
TI  - A national audit of care for myocardial infarction.

PMID- 17007081
TI  - History of cardiology: Etienne-Louis Fallot, MD.

PMID- 17007084
TI  - The elusive stomach ache.

PMID- 17007085
TI  - The biochemical mechanisms of oncogene action: cell surface receptors.

PMID- 17007086
TI  - Anatomy of the transcription apparatus.

PMID- 17007088
TI  - Analyses detect sequence variants.

PMID- 17007087
TI  - Cumulative gene damage can lead to cancer.

PMID- 17007089
TI  - Types of mutations found in BRCA1.

PMID- 17007090
TI  - Reach a consensus.

PMID- 17007091
TI  - Keep options open.

PMID- 17007092
TI  - Gingival vesicle. Gingival cyst of the adult.

PMID- 17007093
TI  - Single versus double wrap.

PMID- 17007094
TI  - Prostate cancer treatment. Permanent low-dose rate prostate brachytherapy.

PMID- 17007095
TI  - [Q & A: A case with fever and hepatosplenomegaly].

PMID- 17007096
TI  - Differential role of slits in dorsal versus ventral retinal axon guidance.

PMID- 17007097
TI  - Federal report documents extensive discrimination against Katrina evacuees with
      psychiatric disabilities.

PMID- 17007098
TI  - Visions and voices: HIV in the 21st century. Indigent persons living with
      HIV/AIDS in the southern USA use photovoice to communicate meaning.

PMID- 17007099
TI  - A weighty issue.

PMID- 17007100
TI  - [A 54-year-old man with a large subcutaneous skull erosion and focal epileptic
      seizures].
AB  - BACKGROUND: Extracranial metastases from meningioma are rare, and are reported to
      occur in less than 1 per 1000. CASE REPORT: We report a 54-year-old man, who
      presented with a parasagittal meningioma with skull erosion and overlying soft
      tissue invasion. Tumour invading the superior sagittal sinus was not removed, and
      postoperative radiation was therefore delivered to the excision site. Histology
      was consistent with an atypical meningioma. The patient had a re-operation of a
      recurrence 3.5 years later, and after another year six tumours were detected
      close to pleura and in the lungs. A biopsy from the largest one demonstrated a
      metastasis having the same histology as the primary tumour. CONCLUSION: Risk
      factors for metastasis of cerebral meningiomas have been suggested to be
      histological malignancy grade, venous sinus invasion, and local recurrences after
      previous craniotomy.

PMID- 17007101
TI  - [Usually good prognosis in meningiomas].

PMID- 17007102
TI  - Comment and reply on: the dose of aspirin for the prevention of cardiovascular
      and cerebrovascular events.

PMID- 17007103
TI  - Effect of lipopolysaccharide and bleeding on the expression of intestinal
      proteins involved in iron and haem transport.
AB  - Haem carrier protein 1 (Hcpl) is a component of the haem-iron uptake pathway in
      the small intestine. Using quantitative real-time PCR, we examined the expression
      of Hcp1 and other intestinal iron-transporting proteins in male C57BL/6 mice with
      experimentally altered iron homeostasis. Intestinal Hcp1 mRNA content was not
      significantly changed by iron overload (600 mg/kg); however, it was increased to
      170 % of controls 72 h after withdrawal of 0.7 ml of blood; the same treatment
      increased intestinal Cybrd1 mRNA to 900 % of controls. LPS treatment (1 mg/kg, 6
      h) decreased intestinal Hcp1 mRNA content to 66 % of controls and Flvcr mRNA
      content to 65 % of controls, while Cybrd1 mRNA, Dmt1 mRNA and Fpn1 mRNA decreased
      to 6 %, 43 % and 32 %, respectively. In 129SvJ mice with targeted disruption of
      the hemojuvelin (Hfe2) gene, which display very low expression of liver hepcidin,
      Cybrd1 mRNA content increased to 1040 %, Dmt1 mRNA content to 200 % and Fpn1 mRNA
      to 150 % when compared to wild-type mice; changes in Hcp1, Abcg2 and Flver mRNA
      content were only minor. Overall, these results suggest that, during
      inflammation, the intestinal haem-iron uptake pathway is not as strongly
      transcriptionally downregulated as the non-haem iron uptake pathway. A decrease
      in circulating hepcidin increases the expression of proteins participating in non
      haem iron uptake, but has no significant effect on Hcp1 mRNA content.

PMID- 17007104
TI  - Apoptosis of cardiomyocytes in myocarditis.
AB  - Apoptosis of cardiomyocytes has been reported to be involved in the pathogenesis
      of heart failure of different aetiologies. The purpose of this study is to assess
      the role and extent of apoptosis of cardiomyocytes in active myocarditis.
      Endomyocardial samples from the right ventricle of 22 patients with active
      myocarditis were compared with 25 traffic accident victims without a history of
      cardiovascular disease. Twenty-two patients fulfilled the histopathologic Dallas
      criteria for myocarditis. The TUNEL method and immunostaining for active caspase
      3 were used for the detection of apoptosis. Immunohistochemical methods were used
      for the evaluation of regulators of apoptosis (p53, Bcl-2) and evaluation of
      interstitial cells (macrophages, T and B lymphocytes). Apoptosis of
      cardiomyocytes (TUNEL-positive and anti-caspase 3-positive cardiomyocytes), which
      was not p53-dependent, was present in 0.3 to 0.4% (0.3% by TUNEL method and 0.4%
      by immunostaining for active caspase 3) of cardiomyocytes in active myocarditis,
      whereas only few apoptotic cardiomyocytes (0.0006 +/- 0.002% TUNEL-positive
      cardiomyocytes and 0.001 +/- 0.002% active caspase 3-positive cardiomyocytes)
      were found in the control group (P = 0.001). Apoptotic (TUNEL-positive and active
      caspase 3-positive) cardiomyocytes were found in small clusters. An increased
      expression of Bcl-2 was found in active myocarditis compared to the controls (P <
      0.01), yet Bcl-2 failed to protect myocytes from apoptosis. We provide evidence
      of apoptosis of cardiomyocytes in active myocarditis, which may be involved in
      the development of heart failure.

PMID- 17007105
TI  - Glycophenotype of psoriatic skin.
AB  - Psoriasis is considered an auto-immune disease with consequential keratinocyte
      hyperproliferation resulting in specific architecture of psoriatic skin. This
      process is associated with phenotypical keratinocyte changes including an altered
      carbohydrate expression pattern studied by labelled plant lectins. Expression of
      endogenous lectins and their reactive glycoligands are differentiation-dependent
      in squamous epithelia including epidermis. However, no data are available on
      psoriatic skin, although this disease represents an important medical problem. We
      investigated the expression of galectin-1, -3, -7 and the presence of their
      glycoligands in the psoriatic skin and compared the results with the normal skin
      samples. The results were correlated to expression patterns of cytokeratin 10 and
      cytokeratin peptide 37 as markers of keratinocyte differentiation as well as to
      the expression of proliferation marker Ki67. Contrary to normal epidermis, the
      psoriatic epithelium expressed no galectin-3 and no glycoligands for galectin-1.
      Strong expression of galectin-3/galectin-3-reactive glycoligands in capillaries
      of psoriatic dermis represents one of the most important findings demonstrating
      the activation of endothelium in the course of the disease. The keratin
      expression pattern was not affected in psoriatic skin compared with normal
      epidermis. In conclusion, the altered galectin expression and binding pattern in
      psoriatic skin indicates the modified process of keratinocyte maturation in
      hyperactivated psoriatic epithelium. The enhanced expression of galectin
      3/galectin-3-reactive glycoligands in dermal capillaries of psoriatic skin can be
      important for rearrangement of the capillary network and migration of
      inflammatory cells to psoriatic skin.

PMID- 17007106
TI  - A karyometric note on nucleoli in human early granulocytic precursors.
AB  - The diameter of nucleoli was measured in human bone marrow early granulocytic
      precursors after visualization by a simple cytochemical method for demonstration
      of RNA. Such method facilitated to clearly see nucleolar bodies without
      perinucleolar chromatin, including those of micronucleoli. The bone marrow of
      patients suffering from chronic myeloid leukaemia (untreated with cytostatics)
      provided a satisfactory number of both myeloblasts and promyelocytes for
      nucleolar measurements because of prevailing granulopoiesis. The direct nucleolar
      measurement was carried out on digitized and processed images on the screen at
      magnification 4,300x. It seems to be likely that the nucleolar size is directly
      related to the number of nucleoli per cell. The largest nucleoli were present in
      both myeloblasts and promyelocytes that possessed a single nucleolus. In
      contrast, the nucleolar diameter was significantly smaller in cells with multiple
      nucleoli. However, in cells with small multiple nucleoli, one of them was always
      larger and dominant with a large number of AgNORs. Such large nucleoli are
      possibly visible in specimens stained with panoptic procedures or methods
      staining nuclear chromatin or DNA. It should also be mentioned that both
      myeloblasts and promyelocytes mostly possessed two nucleoli with the mean
      diameter close to 1.5 microm. The incidence of early granulocytic precursors
      classified according to the nucleolar number and size strongly suggested that the
      various nucleolar number and nucleolar size in these cells might be related to
      the different stage of the cell cycle and might also explain their heterogeneity.

PMID- 17007107
TI  - Elevated and deregulated expression of HDAC3 in human astrocytic glial tumours.
AB  - Abnormal expression of histone deacetylases may contribute to the establishment
      of a cancer specific transcription profile. We examined expression of HDAC3 in
      human non-malignant gliosis and glial astrocytic tumours. Samples from four non
      malignant gliosis and 17 astrocytic gliomas (six of grade II, one of grade III
      and ten of grade IV) removed for therapeutic purposes were assayed for HDAC3
      expression at mRNA and protein levels. HDAC3 mRNA was detected in non-tumorous
      gliosis as well as in all examined glial tumours. Seven out of eleven examined
      high-grade tumours showed an elevated number of copies of HDAC3 mRNA. Western
      blot analysis detected high levels of expression of HDAC3 in the majority of the
      examined tumours. Immunohistochemistry and immunofluorescence made on a
      collection of 35 astrocytic tumours detected nuclear as well as cytoplasmic HDAC3
      expression in all of those tumours. While the distribution of HDAC3 was both
      nuclear as well as cytoplasmic and moderate in intensity in non-malignant tissues
      and low-grade gliomas, high-grade tumours expressed HDAC3 in a focally
      deregulated pattern that included strongly pronounced cytoplasmic localization.
      Confocal microscopy and additional co-localization analysis detected nuclear
      HDAC3 in all tumours examined. We conclude that HDAC3 expression is elevated in
      human astrocytic tumours and its expression pattern is deregulated at the
      cellular level in high-grade gliomas.

PMID- 17007108
TI  - Cell death signalling pathways in the pathogenesis and therapy of haematologic
      malignancies: overview of apoptotic pathways.
AB  - Apoptosis, a Greek descriptive term for falling leaves or petals, plays an
      important role in the progression of many diseases. Apoptosis is essential for
      the development and survival of multi-cellular organisms. Malignant diseases,
      including haematologic malignancies, are associated with defects in the cell
      death mechanism. These defects are not only important for the growth advantage of
      malignant clones, but when understood can be used for specific therapeutic
      targeting of malignant cells while sparing normal cells. The cellular and
      molecular mechanisms of apoptosis have been extensively demonstrated and are
      reviewed in this article. In this part of the review we focus on basic details of
      the apoptosis pathways, key players of the receptor-mediated apoptosis, and
      molecules involved in the cross-talk between individual apoptosis pathways and
      apoptosis regulation.

PMID- 17007109
TI  - Human papillomavirus (HPV) and HPV-associated tumour vaccines.

PMID- 17007110
TI  - Synthetic fragrances perfume lake sediments.

PMID- 17007111
TI  - New consequences of household pesticides.

PMID- 17007112
TI  - Fungi partly disarm asbestos.

PMID- 17007113
TI  - "Fruit farmers, florists, and clockmakers".

PMID- 17007114
TI  - Particulate matter: A strategic vision for transportation-related research.

PMID- 17007115
TI  - Survey of catalysts for oxidation of mercury in flue gas.
AB  - Methods for removing mercury from flue gas have received increased attention
      because of recent limitations placed on mercury emissions from coal-fired utility
      boilers by the U. S. Environmental Protection Agency and various states. A
      promising method for mercury removal is catalytic oxidation of elemental mercury
      (Hg0) to oxidized mercury (Hg2+), followed by wet flue gas desulfurization (FGD).
      FGD cannot remove Hg0, but easily removes Hg2+ because of its solubility in
      water. To date, research has focused on three broad catalyst areas: selective
      catalytic reduction catalysts, carbon-based materials, and metals and metal
      oxides. We review published results for each type of catalyst and also present a
      discussion on the possible reaction mechanisms in each case. One of the major
      sources of uncertainty in understanding catalytic mercury oxidation is a lack of
      knowledge of the reaction mechanisms and kinetics. Thus, we propose that future
      research in this area should focus on two major aspects: determining the reaction
      mechanism and kinetics and searching for more cost-effective catalyst and support
      materials.

PMID- 17007116
TI  - The sediment-water flux of HOCs due to "diffusion" or is there a well-mixed
      layer? If there is, does it matter?
AB  - In most present modeling of the sediment-water flux of hydrophobic organic
      chemicals (HOCs), the flux due to sediment erosion/deposition is described
      explicitly by means of a sediment transport model, while the remaining components
      of the flux (molecular diffusion, bioturbation, and groundwater flow) are lumped
      together and modeled as a "diffusive" flux. This diffusive flux is usually
      described by means of a mass transfer approximation with the implicit assumption
      of a well-mixed contaminant layer of thickness h in the sediments. On the basis
      of recent experiments and theoretical modeling, the justification forthis
      assumption and the quantification of this diffusive flux are discussed here. In
      particular, for HOCs with large partition coefficients, it is argued that a well
      mixed layer often may not exist, and, when it does, it is slow to form; that h is
      difficult to define and even harder to quantify; and that, as far as long-term
      predictions (up to 100 years) of this diffusive flux are concerned, the exact
      value for h probably does not matter. What does matter are the magnitudes and
      time dependencies of each of the components of the flux and the interactions
      between the diffusive flux and the flux due to erosion/deposition.

PMID- 17007117
TI  - Ecological tracers can quantify food web structure and change.
AB  - Disruption of natural food webs is becoming a commonplace occurrence as a result
      of human activities. Considering this, there is a need to improve our ability to
      define food web structure as well as to detect and understand the implications of
      trophodynamic change. This requires the development, validation, and application
      of ecologicaltracers that can provide insights into the movement of energy,
      nutrients, and contaminants through food webs. In this study, we examine the
      utility of two groups of naturally occurring intrinsic tracers (stable nitrogen
      isotopes and fatty acids) to provide such information in a predatory seabird, the
      herring gull (Larus argentatus). Spatial and temporal patterns in gull trophic
      position (inferred from egg stable nitrogen isotope values) were related to gull
      diet composition (inferred from egg fatty acid concentrations). These two
      independent groups of ecological tracers provided corroborating evidence that
      gull trophic position was related to the degree to which aquatic foods, namely
      fish, were consumed. The use of these tracers in concert led to a better
      understanding of routes of energy flow and contaminant transfer in food webs and
      how these pathways may be affected by ecosystem change.

PMID- 17007118
TI  - Adjusting for temporal change in trophic position results in reduced rates of
      contaminant decline.
AB  - The development of ecological tracers to track the flow of energy and nutrients
      through food webs has provided new insights into the factors that are important
      in regulating diet composition in wildlife. The Great Lakes Herring Gull
      Monitoring Program has provided information regarding temporal trends in levels
      of bioaccumulative contaminants since the early 1970s. In recent years, data from
      this program have also been generated to examine ecological changes in the Great
      Lakes. Because the contaminants that are evaluated as part of this program
      biomagnify, food is the primary determinant of contaminant concentrations in the
      eggs that are analyzed annually. Fluctuations in diet composition could affect
      the interpretation of temporal trends by affecting exposure to contaminants.
      Retrospective analyses involving ecological tracers, i.e., stable nitrogen
      isotopes and fatty acids, have shown temporal change in the diets of Great Lakes
      herring gulls at some monitoring colonies. These dietary differences have led to
      temporal variation in the trophic position of herring gulls. Given that higher
      trophic level organisms incur greater exposure to biomagnifying contaminants, it
      is necessary to adjust for these temporal changes in trophic position to get an
      accurate indication of how contaminant burdens are changing within the Great
      Lakes ecosystem. Here, we outline a method to adjust for temporal changes in
      indicator species trophic position and discuss how these adjustments affect the
      interpretation of contaminant temporal trend monitoring data.

PMID- 17007120
TI  - Forensic fingerprinting of diamondoids for correlation and differentiation of
      spilled oil and petroleum products.
AB  - Diamondoids (adamantanes and diamantanes) are rigid, three-dimensionallyfused
      cyclohexyl-ring alkane compounds that can be found in almost all crude oils and
      in most petroleum products. Forforensic environmental investigations, the most
      commonly used biomarkers are high molecular weight (MW) tri- to pentacyclic
      terpanes and steranes. Most of these high MW biomarkers, however, are removed
      from the original crude oil feedstocks during the refining processes, while
      smaller biomarkers including diamondoids are concentrated in petroleum products.
      Fingerprinting diamondoids could thus provide another diagnostic means for
      correlation and differentiation of spilled oils and be particularly valuable for
      light to midrange distillates, such as jet and diesel fuels, the source of which
      may be difficult to identify using routine biomarker techniques. In this work, a
      reliable GC-MS analytical method has been developed for characterization and
      quantitation of diamondoids. The method detection limits for five target
      diamondoids were determined to be in the range of 0.06-0.14 microg/g oil.
      Distributions of diamondoids in over 100 different oils and refined products were
      quantitatively compared. The concentrations of four groups of target biomarkers
      were found, in general, to decrease in the order of sesquiterpanes > terpanes and
      steranes > adamantanes > diamantanes in both crude oils and refined products. A
      number of indices of admantanes and diamantanes have been developed and assessed
      as source indicators using their diagnostic powers (DP). The effects of
      evaporative weathering and biodegradation on alteration of diamondoid
      distributions have been quantitatively investigated. Finally, a spill case study
      by statistical evaluation of diagnostic ratios using the "two-tailed" Student's
      tapproach is presented to illustrate the unique utility of diamondoids for
      correlation and differentiation of unknown spilled diesels.

PMID- 17007119
TI  - Synthetic musk fragrances in Lake Erie and Lake Ontario sediment cores.
AB  - Two sediment cores collected from Lake Ontario and Lake Erie were sectioned,
      dated, and analyzed for five polycyclic musk fragrances and two nitro musk
      fragrances. The polycyclic musk fragrances were HHCB (Galaxolide), AHTN
      (Tonalide), ATII (Traseolide), ADBI (Celestolide), and AHMI (Phantolide). The
      nitro musk fragrances were musk ketone and musk xylene. Chemical analysis was
      performed by gas chromatography/mass spectrometry (GC/MS), and results from Lake
      Erie were confirmed using gas chromatography/triple-quadrupole mass spectrometry
      (GC/MS/MS). The chemical signals observed at the two sampling locations were
      different from each other primarily because of large differences in the
      sedimentation rates at the two sampling locations. HHCB was detected in the Lake
      Erie core whereas six compounds were detected in the Lake Ontario core. Using
      measured fragrance and 210Pb activity, the burden of synthetic musk fragrances
      estimated from these sediment cores is 1900 kg in Lake Erie and 18 000 kg in Lake
      Ontario. The input of these compounds to the lakes is increasing. The HHCB
      accumulation rates in Lake Erie for 1979-2003 and 1990-2003 correspond to
      doubling times of 16 +/- 4 and 8 +/- 2 years, respectively. The results reflect
      current U.S. production trends for the sum of all fragrance compounds.

PMID- 17007122
TI  - Biological oxygen demand dynamics in the lower San Joaquin River, California.
AB  - Dissolved oxygen less than 5 mg L(-1) (U. S. EPA advisory level) commonly occurs
      in the lower San Joaquin River (SJR), California. Most acute episodes typically
      occur in late summer and fall. The oxygen deficit can stress and kill aquatic
      organisms, often inhibiting the upstream migration of Chinook salmon
      (Oncorhynchus tshawytscha). This 5 year study examined watershed-scale spatial
      and temporal biological oxygen demand (BOD) loads and the primary components
      believed to contribute to BOD: ammonium, algal biomass, nonalgal particulate
      organic carbon, dissolved organic carbon, and dissolved organic nitrogen. Samples
      were collected bimonthly at 15 sites during the summers of 2000 and 2001 and from
      three lower mainstem sites from May 2002 to March 2005. BOD loads showed a
      downstream increase in parallel with increasing algal biomass loads resulting
      primarily from in-stream growth. BOD loads from measured tributaries and drains
      accounted for 28% and 39% of the BOD load at the downstream Vernalis site in 2000
      and 2001, respectively. Algal C was positively correlated (r=0.80) with BOD,
      explaining 64% of BOD variance for data collected from 2001 to 2005. Less than
      20% of BOD was found in the dissolved fraction (<0.45 microm). We conclude that
      algal biomass is the primary contributor to BOD loads in the lower SJR, upstream
      of Mossdale.

PMID- 17007121
TI  - Perfluorooctanesulfonate and periluorooctanoate in red panda and giant panda from
      China.
AB  - Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are important
      perfluorochemicals (PFCs) in various applications. Recently, it has been shown
      that these compounds are widespread in the environment, wildlife, and humans. The
      giant panda and the red panda belong to the order Carnivora, but are highly
      specialized as bamboo feeders. Both species are considered rare and endangered.
      In this study, we report for the first time on levels of PFOS and PFOA in serum
      of the giant panda and the red panda captured in zoos and animal parks from six
      provinces in China. PFOS was the predominant compound in all panda samples
      measured (ranging from 0.80 to 73.80 microg/L for red panda and from 0.76 to
      19.00 microg/L for giant panda). The PFOA level ranged from 0.33 to 8.20 microg/L
      for red panda, and from 0.32 to 1.56 microg/L for giant panda. There was a
      positive significant correlation between concentrations of PFOS and PFOA in the
      serum obtained from pandas. No age- or sex- related differences were observed in
      concentrations of the fluorochemicals in panda sera. Greater concentrations of
      the fluorochemicals were found for those individuals collected from zoos near
      urbanized or industrialized areas than for other areas. These data combined with
      other reported data suggest that there are large differences in distribution of
      perfluorinated compounds in terrestrial animals.

PMID- 17007123
TI  - Status of worker exposure to asphalt paving fumes with the use of engineering
      controls.
AB  - Since 1996, industry, labor, and government have partnered to minimize workers'
      exposure to asphalt fumes using engineering controls. The objective of this study
      was to determine the use after some years of experience and to benchmark the
      effectiveness of the engineering controls as compared to the current exposure
      limits. To accomplish this objective, the current highway class pavers equipped
      with controls to reduce asphalt fumes, occupational exposure levels, and
      ventilation flow rates were monitored, and a user acceptance survey was
      conducted. Personal breathing-zone sampling was administered to determine
      concentrations of total particulate matter (TPM) and benzene soluble matter
      (BSM). Personal monitoring of workers yielded a BSM arithmetic mean of 0.13 mg/m3
      (95% confidence limits (0.07, 0.43) mg/m3). All site average worker BSM values
      are below the American Conference of Governmental Industrial Hygienists (ACGIH)
      adopted threshold limit value (TLV) time weighted average (TWA) of 0.5 mg/m3 as
      benzene soluble inhalable particulate, although five sites contained 95%
      confidence limits slightly above the ACGIH TLV. The TPM arithmetic mean was 0.35
      mg/m3 (95% confidence limits (0.27, 0.69) mg/m3). All sites showed average worker
      and area TPM values below NIOSH's recommended exposure limit for asphalt fumes (5
      mg/m3, 15 min). One screed area sample and one operator area sample were also
      taken each day. Area samples followed a similar pattern to the worker breathing
      zone samples, but were generally slightly higher in TPM and BSM concentration.
      The effect of work practices and application temperatures appears to have an
      impact on the ability of the engineering controls to keep exposure below the TLV
      for BSM. To gain a better understanding of the aerodynamic properties of asphalt
      fumes, particle size and airborne concentrations were also monitored using a TSI
      model 3320 aerodynamic particle sizer spectrometer. The geometric mean particle
      size was between 0.64 and 0.98 micrometers for the worker breathing zone samples,
      with a geometric mean of 0.73 micrometers for all sites. Total airborne
      concentrations were typically higher for the asphalt fume exposed groups than for
      the background samples. During high fume events, four 15-minute samples were
      taken each day. Only one 15-minute sample was above the limit of quantification.
      Stack flow rates were measured, and results are discussed and compared to the
      manufacturers' nominal values. Survey results were generally positive, with
      recommendations discussed for continuous improvement.

PMID- 17007124
TI  - Xenoendocrine pollutants may reduce size of sexual organs in East Greenland polar
      bears (Ursus maritimus).
AB  - Reproductive organs from 55 male and 44 female East Greenland polar bears were
      examined to investigate the potential negative impact from organohalogen
      pollutants (OHCs). Multiple regressions normalizing for age showed a significant
      inverse relationship between OHCs and testis length and baculum length and
      weight, respectively, and was found in both subadults (dichlorodiphenyl
      trichloroethanes, dieldrin, chlordanes, hexacyclohexanes, polychlorinated
      biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)) and adults
      (hexachlorobenzene [HCB]) (all p < 0.05). Baculum bone mineral densities
      decreased with increasing chlordanes, DDTs, and HCB in subadults and adults,
      respectively (all p < 0.05). In females, a significant inverse relationship was
      found between ovary length and sigma PCB (p = 0.03) and sigma CHL (p < 0.01),
      respectively, and between ovary weight and sigma PBDE (p < 0.01) and uterine horn
      length and HCB (p = 0.02). The study suggests thatthere is an impact from
      xenoendocrine pollutants on the size of East Greenland polar bear genitalia. This
      may pose a riskto this polar bear subpopulation in the future because of reduced
      sperm and egg quality/quantity and uterus and penis size/robustness.

PMID- 17007125
TI  - Changing chemical composition of precipitation in Wilmington, North Carolina,
      U.S.A.: implications for the Continental U.S.A.
AB  - The H+(aq) concentration in Wilmington, NC, precipitation has decreased by
      approximately 50% during the preceding two decades, similar to trends seen
      nationwide. The decrease in acidity is important because solution pH plays a key
      role in atmospheric reactions, and because the change is so large. This study
      presents the first long-range study of dissolved organic carbon (DOC) levels in
      precipitation which demonstrates that DOC concentrations have decreased by
      approximately half in Wilmington, NC, precipitation. The concentrations of H+(aq)
      and DOC are highly correlated primarily because small organic acids contribute to
      both DOC and H+(aq) in precipitation. Ammonium ion concentrations in
      precipitation have increased due to increased agricultural activities, and this
      also affects precipitation pH. The reduction of SO2 emissions in 1995 imposed by
      the Clean Air Act Amendment, better control of emissions of volatile organic
      compounds, and the increase in ammonia emissions all contribute to the decreasing
      H+(aq) in precipitation nationwide. These compositional changes in precipitation
      have many environmental implications, such as decreased acid deposition to lakes,
      changing speciation for trace metals in precipitation, increased ammonium
      deposition to coastal waters, and decreased DOC transport to the open ocean.

PMID- 17007126
TI  - Role of weathered coal tar pitch in the partitioning of polycyclic aromatic
      hydrocarbons in manufactured gas plant site sediments.
AB  - Polycyclic aromatic hydrocarbons (PAHs) in manufactured gas plant (MGP) site
      sediments are often associated with carbonaceous particles that reduce
      contaminant bioavailability. Although black carbon inclusive partitioning models
      have been proposed to describe elevated PAH partitioning behavior, questions
      remain on the true loading and association of PAHs in different particle types in
      industrially impacted sediments. In the studied MGP sediments, the light density
      organic particles (coal, coke, wood, and coal tar pitch) comprised 10-20% of the
      total mass and 70-95% of the PAHs. The remainder of the PAHs in sediment was
      associated with the heavy density particles (i.e., sand, silt, and clays). Among
      the different particle types, coal tar pitch (quantified by a quinoline
      extraction method) contributed the most to the bulk sediment PAH concentration.
      Aqueous partition coefficients for PAHs measured using a weathered pitch sample
      from the field were generally an order of magnitude higher than reported for
      natural organic matter partitioning, and match well with theoretical predictions
      based on a coal tar-water partitioning model. A pitch-partitioning inclusive
      model is proposed that gives better estimates of the measured site-specific PAH
      aqueous equilibrium values than standard estimation based on natural organic
      matter partitioning only. Thus, for MGP impacted sediments containing weathered
      pitch particles, the partitioning behavior may be dominated by the sorption
      characteristics of pitch and not by natural organic matter or black carbon.

PMID- 17007127
TI  - Zinc coordination to multiple ligand atoms in organic-rich surface soils.
AB  - We report on the solid-phase speciation of naturally occurring Zn in
      metalliferous organic-matter-rich surface soils. Synchrotron-based studies were
      used to probe elemental distribution and associations in soil particles (micro
      XRF) together with the mineralogy (micro-XRD) and Zn bonding environment (Zn
      micro-XANES) at the micrometer-scale level. The average bonding environment of Zn
      was also probed for bulk soils using XANES. We found the distribution of elements
      within soil particles to be heterogeneous; however, some elements are
      consistently co-located. While conventional XRD analyses of whole soils did not
      identify any Zn mineral phase, synchrotron-based-micro-XRD analyses indicated
      that sphalerite (ZnS) is present in a particle from a wetland soil (soil labeled
      G3). Linear combination fit (LCF) analyses of XANES spectra collected for bulk
      soils (Zn-XANES) and microm-regions (Zn-micro-XANES) within soil particles
      suggest Zn bonds to oxygen-, nitrogen-, and sulfur-functional groups in these
      sulfur-, nitrogen-, and zinc-rich organic surface soils. The XANES spectra of all
      bulk soils and of all microm-regions except for the wetland soil (G3), where ZnS
      was the most significant constituent, were best fitted by the Zn-arginine
      reference compound and therefore seems to indicate Zn bonding to nitrogen. Thus,
      these results provide compelling evidence of the formation of highly covalent Zn
      organic bonds in the organic-rich surface soils that were studied. This may
      explain in part why metal partition coefficients (Kd) are generally higher in
      organic soils, and why the toxic thresholds for total metal concentrations are
      higher in organic than in mineral soils.

PMID- 17007128
TI  - Quantification of particle number and mass emission factors from combustion of
      Queensland trees.
AB  - The quantification of particle emission factors under controlled laboratory
      conditions for burning of the following five common tree species found in South
      East Queensland forests has been studied: Spotted Gum (Corymbia citriodora), Blue
      Gum (Eucalyptus tereticornis), Bloodwood (Eucalyptus intermedia), Iron Bark
      (Eucalyptus crebra), and Stringybark (Eucalyptus umbra). The results of the study
      show that the particle number emission factors and PM2.5 mass emission factors
      depend on the type of tree and the burning rate. For fast burning conditions, the
      average particle number emission factors are in the range of 3.3-5.7 x 10(15)
      particles/kg for woods and 0.5-6.9 x 10(15) particles/kg for leaves and branches,
      and the PM2.5 emission factors are in the range of 140-210 mg/kg for woods and
      450-4700 mg/kg for leaves and branches. For slow burning conditions, the average
      particle number emission factors are in the range of 2.8-44.8 x 10(13)
      particles/kg for woods and 0.5-9.3 x 10(13) particles/kg for leaves and branches,
      and the PM2.5 emissions factors are in the range of 120-480 mg/kg for woods and
      3300-4900 mg/kg for leaves and branches.

PMID- 17007129
TI  - Stimulatory and inhibitory effects of organohalides on the dehalogenating
      activities of PCB-dechlorinating bacterium o-17.
AB  - Bacterium o-17, a microorganism capable of the ortho dechlorination of 2,3,5,6
      polychlorinated biphenyl (PCB), is a member of a sediment-free, nonmethanogenic
      mixed culture. The culture was examined for the ability to dechlorinate 26 PCB
      congeners, 12 chlorobenzenes (CBZs), and 6 chlorinated ethenes (CEs). Eight of
      the PCBs and 4 of the CBZs were dechlorinated including single-flanked ortho PCB
      chlorines, but double-flanked chlorines of PCBs and CBZs were preferentially
      dechlorinated. The dechlorination of three of the PCBs (2,3,4,5,6-, 2,3,4,6-, and
      2,3,5,6-PCB), three of the CBZs (hexa-, penta-, and 1,2,3-CBZ), and PCE could be
      sustained for three or more sequential transfers of the bacterial community. Two
      PCBs (2,3,4- and 2,3,5-PCB), two CBZs (1,2,3,5- and 1,2,4,5-CBZ), and
      trichloroethene were dechlorinated only when a more extensively chlorinated
      parent compound was present. Aroclor 1260 and 2,4,6-PCB, not dechlorinated by the
      culture, inhibited the dechlorination of 2,3,5,6-PCB. Within the culture only
      bacterium o-17 was linked to dechlorination by PCR-DGGE analysis, confirming that
      this dehalogenating species was the catalyst for the dechlorination of the
      compounds tested. The microorganism is capable of dechlorinating several
      different congeners of PCBs, CBZs, and CEs, and it remains a rare example of an
      ortho-PCB dechlorinator. However, its limited ability to dechlorinate more
      extensively chlorinated congeners and Aroclor plus the inhibitory effects of some
      PCB congeners upon the bacterium is consistent with the observed infrequency of
      this reaction in the environment. An assessment of bioremediation potential of
      this microorganism in situ will require a greater understanding of the
      synergistic, cometabolic and competitive interactions of PCB dechlorinating
      microbial communities.

PMID- 17007130
TI  - Differential E. coli die-off patterns associated with agricultural matrices.
AB  - The investigation of fecal bacterial die-off in various agricultural and
      catchment related matrices remains important because of the growing concern over
      pathogens in agricultural environments and watercourses. The aim of this research
      was to investigate the die-off of Escherichia coli within cattle manure (both
      slurry [liquid mix of excrement and urine produced by housed livestock] and
      feces), soil, and runoff water and to determine if cell numbers would be
      influenced by the presence of cattle manure within soil and runoff water. E. coli
      survived better within feces than in slurry; cells within feces declined from 7.5
      to 3.3 log CFU g(-1) in 76 days. Within slurry, cells fell from 8.5 log CFU g(-1)
      to below levels of detection by day 42. E. coli died off more quickly within
      manure and slurry than in soil amended with the same fecal material, and declined
      significantly faster within microcosms when introduced to the soil via sterile
      water rather than cattle manure. E. coli was found to decline more rapidly within
      wet (50% moisture w/w), rather than dry (25% moisture w/w), soil. Conversely, in
      runoff water, die-off of E. coli was increased in the presence of feces. Overall,
      E. coli die-off was most rapid in water incorporated with cattle manure >
      unincorporated cattle manure > soil incorporated with cattle manure. The derived
      die-off characteristics including half-life and decimal reduction times can now
      provide (i) input for predictive models and (ii) information upon which to
      consider mitigation strategies associated with both manure and land management.

PMID- 17007131
TI  - Kinetics and mechanism of degradation of dichlorvos in aqueous solutions
      containing reduced sulfur species.
AB  - Reactions of dichlorvos with five reduced sulfur species (hydrogen sulfide,
      bisulfide, thiosulfate, thiophenol, and thiophenolate) were examined in well
      defined anoxic aqueous solutions to investigate their role in its degradation.
      Reactions were monitored at varying concentrations of reduced sulfur species over
      pH range to obtain the second-order reaction rate constants. Experiments at 25
      degrees C demonstrated that degradation of dichlorvos promoted by bisufide,
      thiosulfate, and thiophenolate were of much greater importance than hydrolysis
      under the experimental conditions in our study. In contrast, hydrogen sulfide and
      thiophenol were not effective in the degradation of dichlorvos. The activation
      parameters of the reaction of dichlorvos with bisulfide, thiosulfate, and
      thiophenolate were also determined from the measured second-order rate constants
      over a temperature range of 12-50 degrees C. The relative reactivity of the
      reduced sulfur species decreases in the following order: PhS- > HS- approximately
      equal to S2O3(2-). When the second-order rate constants at 25 degrees C are
      multiplied by the environmentally relevant concentration of the reduced sulfur
      species, predicted half-lives of dichlorvos ranged from hours to days. The
      results indicated that reduced sulfur species could play a very important role in
      the chemical fate of dichlorvos in coastal marine environments.

PMID- 17007132
TI  - Experimental measurement of proton, Cd, Pb, Sr, and Zn adsorption onto the fungal
      species Saccharomyces cerevisiae.
AB  - Proton, Cd, Pb, Sr, and Zn adsorption onto the fungal species Saccharomyces
      cerevisiae were measured in bulk adsorption experiments as a function of time,
      pH, surface: metal ratio, and ionic strength, and we measured the electrophoretic
      mobility of the cells as a function of pH. We modeled the acid/base properties of
      the fungal cell wall by invoking a nonelectrostatic surface complexation model
      with four discrete surface organic acid functional group types, with average pKa
      values (with 1 sigma uncertainties) of 3.4 +/- 0.4, 5.0 +/- 0.2, 6.8 +/- 0.4, and
      8.9 +/- 0.6. The affinity of the fungal cells for the metal ions follows the
      following trend: Pb > Zn > Cd > Sr. We used the metal adsorption data to
      determine site-specific stability constants for the important metal fungal
      surface complexes. Our results suggest that S. cerevisiae may represent a novel
      biosorbent for the removal of heavy metal cations from aqueous waste streams.

PMID- 17007133
TI  - Arsenic sequestration in iron plaque, its accumulation and speciation in mature
      rice plants (Oryza sativa L.).
AB  - A compartmented soil-glass bead culture system was used to investigate
      characteristics of iron plaque and arsenic accumulation and speciation in mature
      rice plants with different capacities of forming iron plaque on their roots. X
      ray absorption near-edge structure spectra and extended X-ray absorption fine
      structure were utilized to identify the mineralogical characteristics of iron
      plaque and arsenic sequestration in plaque on the rice roots. Iron plaque was
      dominated by (oxyhydr)oxides, which were composed of ferrihydrite (81-100%), with
      a minor amount of goethite (19%) fitted in one of the samples. Sequential
      extraction and XANES data showed that arsenic in iron plaque was sequestered
      mainly with amorphous and crystalline iron (oxyhydr)oxides, and that arsenate was
      the predominant species. There was significant variation in iron plaque formation
      between genotypes, and the distribution of arsenic in different components of
      mature rice plants followed the following order: iron plaque > root > straw >
      husk > grain for all genotypes. Arsenic accumulation in grain differed
      significantly among genotypes. Inorganic arsenic and dimethylarsinic acid (DMA)
      were the main arsenic species in rice grain for six genotypes, and there were
      large genotypic differences in levels of DMA and inorganic arsenic in grain.

PMID- 17007134
TI  - Biodegradation of synthetic base fluid surrogates in Gulf of Mexico sediments
      under simulated deep-sea conditions.
AB  - In this study, an anaerobic marine biodegradability test was adapted to study the
      fate of synthetic base fluid (SBF) surrogates, ethyl oleate and tetradecene, by
      deep-sea microorganisms. Sediment samples from hundreds of meters deep in the
      Gulf of Mexico were incubated at low temperatures (4 degrees C) and high
      hydrostatic pressure in steel vessels. Stimulation of indigenous microbial
      communities to SBF biodegradation was evident in the fact that the rate of
      removal of ethyl oleate was greater in sediments that had some previous exposure
      to SBF (first-order decay coefficient kof -0.22 +/- 0.02 week(-1)) compared to
      unexposed control sediments (first-order decay coefficient k of -0.11 +/- 0.02
      week(-1)). When sulfate-linked tetradecene degradation occurred within the test
      period, the activity could also be modeled as a first-order decay following an
      initial lag phase, with an average decay coefficient of k = -0.05 +/- 0.01 week(
      1). This study also revealed that the degradation of SBF surrogates by
      microorganisms collected from deep-sea sediments was not significantly effected
      by the hydrostatic incubation pressure.

PMID- 17007135
TI  - Colloid mobilization during soil iron redox oscillations.
AB  - In redox-dynamic soils, iron reduction-oxidation events may initiate wide shifts
      in the concentration of colloidal and dissolved material because of either Fe
      mineral dissolution or pH shifts associated with Fe oxidation state changes. This
      can have profound effects on the mobilization of organic and metal constituents.
      We conducted laboratory studies of colloid dynamics in a Hawaiian soil subjected
      to four consecutive 14-day reduction-oxidation cycles across the "soil-Fe"
      (Fe(OH)3)/(Fe2+(aq)) equilibrium. Size fractionated samples were isolated by
      differential centrifugation and characterized based on analysis of the framework
      and trace elements (Si, C, Fe, Ti, Al, Zr, Nb, La, and U). Intracycle
      oscillations in all colloidal (3 kDa to 160 nm) elements peaked during the
      reduction half-cycles, mobilizing 10% of total soil Ti and from 1-5% of total
      soil Zr, Nb, La, and U at peak dispersion. Colloid dynamics were dependent on pH
      shifts accompanying the redox oscillations rather than the fluctuating solubility
      of Fe oxides. TEM/EDS and mass-balance calculations suggest a carbon-based
      colloid matrix with zones of metal enrichment. The cumulative effects of four
      redox cycles included an apparent increase in colloid stability. Proton
      production/consumption associated with Fe-redox cycling has important
      implications for mobilization colloid-borne trace elements and sorbed
      contaminants.

PMID- 17007136
TI  - Isotopic evidence in tree rings for historical changes in atmospheric sulfur
      sources.
AB  - Little is understood about the usefulness of sulfur isotopic ratios (sigma 34S)
      in tree rings because the sulfur content in rings is generally insufficient for
      analysis using conventional methods. We present sigma 34S values of the water
      soluble and the organically bound sulfur fractions in rings of coniferous trees
      grown in Japan, analyzed using a large-volume oxygen bomb. Comparing the sigma
      34S values of the organically bound fraction in tree rings with past atmospheric
      sulfur concentrations and with those of their sources, we find clear evidence
      that the sigma 34S values of the organically bound fraction in the rings are
      dependent upon the values of the atmospheric sulfur sources. The evidence
      suggests that the sigma 34S values in tree rings are a useful chronological proxy
      for evaluating possible causes of past atmospheric sulfur pollution.

PMID- 17007137
TI  - Comparison of ultraviolet absorbance, chemiluminescence, and DOAS instruments for
      ambient ozone monitoring.
AB  - This paper evaluates the accuracy of ozone measurements made by monitors that
      determine ozone concentrations in ambient air by UV absorption. These monitors
      are typically used to measure ozone for the purpose of establishing local
      compliance to air-quality standards. The study was predicated by the concern that
      commercially available UV absorbance O3 monitors may be subject to interference
      from volatile organic carbon (VOC) species that absorb light at 254 nm. To test
      for these and other effects, we compared simultaneous O3 measurements made by a
      commercial UV O3 monitor with an O3-NO chemiluminescence instrument, which is not
      subject to interference by VOC compounds. The comparisons were carried out in the
      summers of 1999 and 2000 at urban/industrial sites in Nashville and Houston, and
      in 2004 aboard a ship in the Gulf of Maine. In the two urban areas, we also
      compared the 03 measurements from these two methods with O3 measurements made by
      a long-path differential optical absorption spectrometer (DOAS). Our tests
      indicate that, with well-maintained monitors, there are no significant
      interferences even in areas with significant ambient concentrations of
      potentially interfering VOCs.

PMID- 17007139
TI  - On-board generation of a highly volatile starting fuel to reduce automobile cold
      start emissions.
AB  - The on-board distillation system (OBDS) was developed to extract, from gasoline,
      a high-volatility fuel for exclusive use during the starting and warm-up periods.
      The use of OBDS distillate fuel results in much improved mixture preparation,
      allowing combinations of air/fuel ratio and ignition timing that are not possible
      with gasoline, even with a fully warm engine. The volatility of the distillate is
      a function of the parent fuel volatility; however, the variability in distillate
      quality can be diminished via manipulation of the OBDS operating conditions.
      Thus, it is possible to develop aggressive starting calibrations that are
      relatively immune to variations in pump gasoline volatility. The key benefits
      provided bythe OBDS fuel relative to standard gasoline were found to be (1)
      improved mixture preparation allowing a 70% reduction of cranking fuel
      requirements, elimination of air-fuel mixture enrichment during the warm-up
      period, and significant extension of warm-up ignition timing retard; (2) a 57%
      decrease in catalyst light-off time, (3) emissions reductions over the FTP drive
      cycle of 81% for regulated hydrocarbons (NMOG); (4) emissions index (NMOG)
      approaching that of SULEV/PZEV vehicles; and (5) an apparent 1% increase in fuel
      economy over the FTP drive cycle.

PMID- 17007138
TI  - High temporal resolution oxygen imaging in bioirrigated sediments.
AB  - A technique is presented for temporal characterization of the bioirrigation
      activity of benthic macrofauna and for quantitative estimation of its effects on
      the oxygen exchange between the sediment and the overlying water. The technique
      is based on high temporal resolution (15-30 s) oxygen imaging aided by a planar
      oxygen optode and can be applied under laboratory and field conditions, both
      freshwater and marine. It allows direct observation of the complex 2D oxygen
      dynamics in the sediment around the burrow while the animal dwells undisturbed in
      its natural environment. The conditions to which the animal is exposed can easily
      be controlled or manipulated. Chironomus plumosus, widely distributed freshwater
      insect larvae, were used in a case study. Their bioirrigation activity was
      divided into a random succession of pumping intervals (duration 5.4 +/- 1.7 min)
      and rest periods (duration 9.2 +/- 5.8 min). The burrow ventilation resulted in a
      highly variable volume of the oxygenated sediment surrounding the burrow and the
      associated sedimentary oxygen uptake rate through the burrow wall (OUB), both
      changing dramatically within minutes. Their variability was higher in a burrow
      under construction than around a stationary burrow. The average OUB rate
      (approximately 0.15 micromol O2 h(-1)), when translated into a time-averaged 02
      flux across the burrow wall, constituted approximately 64% of the stationary
      diffusive oxygen flux measured at the sediment-water interface (approximately0.9
      mmol O2 m(-2) h(-1)).

PMID- 17007140
TI  - An experimental and kinetic modeling study of the reaction of CHF3 with methane.
AB  - The gas-phase reaction of CHF3 with CH4 has been studied experimentally and
      computationally. The motivation behind the study is that reaction of CHF3 with
      CH4 provides a possible route for synthesis of CH2=CF2 (C2H2F2). Experiments are
      carried out in a plug flow, isothermal alpha-alumina reactor at atmospheric
      pressure over the temperature range of 973-1173 K. To assist in understanding the
      reaction mechanism and the role of the reactor material involved in the reaction
      of CHF3 with CH4, the reaction of CHF3 with CH4, pyrolysis of CH4, and pyrolysis
      of CHCIF2 have been studied in the presence of alpha-alumina or alpha-AIF3
      particles under various conditions. Under all conditions studied for the reaction
      of CHF3 and CH4, the major products are C2F4, C2H2F2, and HF. Minor products
      include C2H2, C2H4, C2H3F, C2HF3, C3F6, CO2, and H2. C2H6, CH2F2, and CHF2CHF2
      are detected in trace amounts. The initial step is the gas-phase unimolecular
      decomposition of CHF3, producing CF2 and HF. It is proposed that CF2 decomposes
      on the surface of alpha-alumina, producing F radicals that are responsible for
      the activation of CH4. A reaction scheme developed on the basis of the existing
      NIST HFC and GRI-Mech 3.0 mechanisms is used to model the reaction of CHF3 with
      CH4. Generally satisfactory agreement between experimental and modeling results
      is obtained on the conversion levels of CHF3 and CH4 and rates of formation of
      major products. Using the software package AURORA, the reaction pathways leading
      to the formation of major products are elucidated.

PMID- 17007141
TI  - Ettringite-induced heave in chromite ore processing residue (COPR) upon ferrous
      sulfate treatment.
AB  - A pilot-scale treatment study was implemented at a deposition site of chromite
      ore processing residue (COPR) in New Jersey. Ferrous sulfate heptahydrate (FeSO4
      x 7H2O) was employed to reduce hexavalent chromium in two dosages with three
      types of soil mixing equipment. XANES analyses of treated samples cured for 240
      days indicated that all treatment combinations failed to meet the Cr(VI)
      regulatory limit of 240 mg/kg. More importantly, the discrepancy between XANES
      and alkaline digestion results renders the latter unreliable for regulatory
      purposes when applied to ferrous-treated COPR. Regardless of Cr-(VI), the
      introduction of reductant containing sulfate, mechanical mixing, water, acidity,
      and the resulting temperature increase in treated COPR promoted dissolution of
      brownmillerite (Ca2FeAlO5), releasing alumina and alkalinity. The pH increase
      caused initially precipitated gypsum (CaSO4 x 2H2O) to progressively convert to
      ettringite (Ca6Al2(SO4)3 x 32H2O) and its associated volume expansion under both
      in situ and ex situ conditions, with a maximum of 0.8 m vertical swell within 40
      days of curing. While Cr-(VI) treatment remains a challenge, the intentional
      exhaustion of the heave potential of COPR by transforming all Al sources to
      ettringite emerges as a possible solution to delayed ettringite formation, which
      would hamper site redevelopment.

PMID- 17007142
TI  - Soil fungi reduce the iron content and the DNA damaging effects of asbestos
      fibers.
AB  - Some soil fungi growing on asbestos fibers release chelators and antioxidants.
      The bioweathering potential of fungi has thus been envisaged as a possible route
      for bioremediation of asbestos rich soils, where no inactivation procedures have
      been established so far. The present study reports fungal-mediated modification
      of the surface reactivity of the fibers and of their potential to damage DNA in
      vitro. Verticillium sp. and Paecilomyces sp. were selected among the fungi
      isolated from fragments of chrysotile bearing rocks, as the most potent in iron
      extraction, and studied in parallel with F. oxysporum, previously reported to
      modify the surface reactivity of asbestos fibers. One sample of chrysotile from
      the Western Alps and a sample of UICC (Union Internationale Contre le Cancer)
      crocidolite were incubated with or without fungi. All fungi extracted iron from
      both fibers (7.3% from crocidolite and 33.6% from chrysotile by Verticillium
      sp.), releasing it into the medium. F. oxysporum and Paecilomyces sp. suppressed
      the potential of the fibers to release hydroxyl radical, while Verticillium sp.
      suppressed it on crocidolite but enhanced it on chrysotile, a hallmark of ongoing
      mobilization of reactive iron. Fibers incubated in the growth medium, but in the
      absence of fungi, exhibited a remarkable potential to damage DNA in vitro,
      measured by the generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, while all the
      fungi reduced such effect. Fungi may thus be regarded as appropriate candidates
      for bioremediation of asbestos rich soils whereby the reactive iron ions
      responsible for DNA damage are progressively removed from the fibers.

PMID- 17007143
TI  - Efficient decomposition of benzene over a beta-Ga2O3 photocatalyst under ambient
      conditions.
AB  - A porous beta-Ga2O3 photocatalyst has been successfully prepared. The
      photocatalyst was characterized by XRD, N2 adsorption-desorption, TEM, UV/vis,
      and FTIR techniques. The photocatalytic activity of the sample was evaluated by
      the decomposition of benzene in air under UV light illumination and was compared
      with that of the commercial titania (Degussa P25) and Pt/P25. Results revealed
      that the synthesized Ga2O3 was porous beta-Ga2O3 and was highly photoactive for
      mineralizing benzene and its derivatives (e.g., toluene and ethylbenzene) to CO2
      under ambient conditions. The photocatalytic conversion of benzene over beta
      Ga2O3 was about 1 order of magnitude higher than that over P25, and no obvious
      deactivation of beta-Ga2O3 was observed during the prolonged operation of 80 h.
      The high activity and long-term stability of the Ga2O3 have been ascribed to its
      stronger oxidative capability and higher specific surface area in comparison with
      P25.

PMID- 17007144
TI  - Competitive sorption of pyrene, phenanthrene, and naphthalene on multiwalled
      carbon nanotubes.
AB  - Knowledge of toxic chemical sorption by carbon nanotubes (CNTs) is critical for
      environmental application of CNTs as superior sorbents and for environmental risk
      assessment of both CNTs and toxic chemicals. Single-solute sorption results were
      reported in the literature, however, they cannot be used for predicting pollutant
      sorption by CNTs in wastewater and natural water systems where multiple organic
      contaminants are present. In this study, competitive sorption of pyrene,
      phenanthrene, and naphthalene on a multiwalled CNT material was investigated. All
      isotherms in single-, bi-, and tri-solute systems were fitted well by the Dubinin
      Ashtakhov (DA) model. The isotherm of a given primary solute changed from being
      significantly nonlinear to nearly linear when competitors were added. The
      observed competitive sorption depended on the relative equilibrium concentrations
      of both primary and cosolutes. Significant competition was observed at relatively
      low concentrations of primary solute and high concentrations of competitors,
      while competition was much weaker in the case of relatively high concentrations
      of primary solute and low competitor concentrations. When the relative
      concentration of primary solute (Ce/Cs) approached 1, competition by other
      solutes seemed to disappear. Sorption and competition of three polycyclic
      aromatic hydrocarbons (PAHs) on CNTs could not be explained with either pore
      filling or partition-adsorption mechanisms. A Polanyi-based surface adsorption
      mechanism was proposed to interpret the observed sorption and competition.

PMID- 17007145
TI  - Elimination of pharmaceuticals and personal care products in subsurface flow
      constructed wetlands.
AB  - Removal efficiency and elimination rates of 11 pharmaceuticals and personal care
      products (PPCPs)were measured in two subsurface horizontal flow constructed
      wetlands (SSFs) characterized by different water depths (i.e. 0.3 and 0.5 m) in a
      2-year study. Dissolved and particulate phases of wastewater and gravel samples
      were collected and analyzed. The PPCP influent concentration ranged from 1 to 25
      microg L(-1). The best removal efficiency was found in the shallower bed SSF due
      to its less negative redox potential. PPCPs were classified in four groups
      according to their removal behavior: (i) the efficiently removed (>80%) namely
      caffeine, salicylic acid, methyl dihydrojasmonate, and carboxy-ibuprofen, (ii)
      the moderately removed (50-80%) namely ibuprofren, hydroxy-ibuprofen, and
      naproxen, (iii) the recalcitrant to the elimination namely ketoprofen and
      diclofenac, and,finally, (iv) compounds that were eliminated by hydrophobic
      interactions namely polycyclic musks (i.e. galaxolide and tonalide). These
      compounds were removed more than 80% from the effluent but occurred at high
      concentrations (up to 824 microg kg(-1)) in the gravel bed. Accordingly, their
      elimination by sorption onto the organic matter retained is the predominant
      removal mechanism. Furthermore, the constructed wetland clogging appears to
      induce a negative effect in the PPCP degradation in the SSF evaluated. The PPCP
      elimination classified as efficiently and moderately removed through the shallow
      bed fitted to either zero- or a first-order areal kinetics. Finally, the apparent
      distribution coefficients between suspended solids (Kd'ss) or gravel bed (Kd'gb)
      and water were determined in the different sampling points of the wetland
      obtaining values comparable to the described previously for sewage sludge.

PMID- 17007146
TI  - Aquatic effects of aerial spraying for mosquito control over an urban area.
AB  - In an effort to combat West Nile Virus, planes dispersed insecticide over
      Sacramento, CA, treating nearly 50,000 hectares with pyrethrins and the synergist
      piperonyl butoxide (PBO). Widespread dispersal of insecticide over a metropolitan
      area, coupled with extensive pretreatment data on the area's urban creeks,
      provided a unique opportunity to study effects of mosquito control agents on
      aquatic habitats within an urban setting. There was no evidence of aquatic
      toxicity from the two active ingredients in the product applied. However, PBO
      concentrations were high enough to enhance toxicity of pyrethroids already
      existing in creek sediments from general urban pesticide use. PBO concentrations
      of 2-4 microg/L were high enough to nearly double the toxicity of sediments to
      the amphipod Hyalella azteca. Though the increase in toxicity was modest, it was
      unexpected to find environmental synergy at all. Risk assessments for mosquito
      control agents have focused on the active ingredients but have failed to
      recognize the potential for interactions with pesticides previously existing in
      the environment, which in this case appeared to represent a risk to aquatic life
      greater than that of the active ingredients themselves.

PMID- 17007147
TI  - Sharps safety devices.
AB  - Injuries from needles or other sharps are a danger to patients and clinicians
      alike, particularly due to the risk of bloodborne pathogen transmission. One way
      to reduce the likelihood of such injuries is to implement protective devices as
      substitutes for more dangerous conventional products. Over the years, Health
      Devices has evaluated several sharps safety devices. In this issue, we evaluate
      four new types of protective alternatives: disposable prep razors, epidural
      needles, ophthalmic knives, and stitch cutters. Our Evaluation discusses whether
      these sharps safety devices deliver the added safety that they are designed to
      provide and whether they are effective at performing their intended clinical
      purposes.

PMID- 17007148
TI  - Sharps safety. Five steps for maintaining an effective program.
AB  - Although most hospitals have had sharps safety programs in place for years, these
      programs may be out of date or may fail to address new procedures. Facilities
      should therefore regularly take stock of their current practices and evaluate new
      devices on the market. In this article, we describe a five-step process for
      developing, assessing, or revising a sharps safety program. Such programs are
      typically broad based, addressing several types of risks and the activities of
      multiple departments. Facilities may have well-established procedures for dealing
      with one of these aspects, while having few if any measures in place to address
      another. Consequently, the steps in the program described in this article may
      need to be applied in different ways to different areas within a single hospital.
      Yet even well-established programs require ongoing review, so these five steps
      are recommended regardless of how complete or effective a facility's current
      efforts may seem.

PMID- 17007149
TI  - Do positive fluid-displacement Luer-activated devices increase infection rates?
      The jury is still out.
AB  - Luer-activated devices (LADs) are needleless connectors that allow access to
      intravenous systems. There have been anecdotal reports that one type of LAD,
      which uses a positive fluid-displacement (PFD) design, has been associated with
      elevated rates of catheter-related bloodstream infections (CR-BSIs). As yet,
      however, there isn't enough scientific evidence to conclusively demonstrate a
      link between PFD LADs and CR-BSIs. (Shown at right are three examples of PFD
      LADs. No one design, model, or manufacturer of these devices has been
      particularly associated with CR-BSIs.) In this article, we explain why detecting
      the problem can be so difficult and outline some steps healthcare facilities can
      take to identify LAD-related infections. And we describe a survey we've placed on
      our Web site to collect data on LADs and infection rates, including changes in
      rates following a change of device type.

PMID- 17007150
TI  - Hazard report. Calf supports on Hill-Rom Affinity Three birthing beds may shift
      unexpectedly.

PMID- 17007151
TI  - User experience network. Hill-Rom stretchers may need upgrade of fifth-wheel
      steering assembly.

PMID- 17007152
TI  - Culturally responsive interventions to enhance immunosuppressive medication
      adherence in older African American kidney transplant recipients.
AB  - CONTEXT: Immunosuppressive medication nonadherence is variable among older kidney
      transplant recipients and is a problem in African American recipients despite the
      severe consequences of this behavior. Many factors place older African American
      recipients at risk for medication nonadherence. OBJECTIVE: To provide an overview
      of interventions to enhance immunosuppressive medication adherence in older
      African American kidney transplant recipients using a culturally responsive
      model. Culturally sensitive, innovative, and transformation interventions are
      discussed. Situations when each intervention would be most and least appropriate
      are described. CONCLUSION: Moving culturally appropriate interventions forward
      into practice and testing their effectiveness in improving adherence outcomes in
      vulnerable, older African American kidney transplant recipients is a worthy
      practice and research goal for transplant nursing.

PMID- 17007153
TI  - Analysis of morbidity in liver transplant recipients following human albumin
      supplementation: a retrospective pilot study.
AB  - OBJECTIVES: To assess incidence of morbidity (i.e., documented infection, acute
      renal failure, acute graft rejection, acute cardiovascular events, and hospital
      readmission rates) 6 months following liver transplantation using linear
      regression as a function of cumulative albumin dose. DESIGN: Retrospective chart
      review. SETTING: A 473-bed tertiary care teaching facility with a solid-organ
      transplantation center. PATIENTS: Forty liver transplant recipients examined from
      January 1 to December 31, 2003. MEASUREMENTS AND RESULTS: Data from 40 liver
      transplant recipients were collected. Mean albumin dose administered was 190.9 +/
      162.3 g. No statistical differences were identified in patients receiving less
      than 140 g (n=20) or more than 140 g (n=20) with respect to demographic data
      other than gender and ethnicity. The mean APACHE III (Acute Physiology and
      Chronic Health) score was 69.7 +/- 24.3. Approximately 70 episodes of morbidity
      and 23 readmissions were observed. Regardless of the APACHE III score, albumin
      was associated with increased overall morbidity and cardiovascular complications.
      Liver transplant recipients receiving more than 140 g had a longer hospital stay
      (14 vs. 8 days, P = .025) and intensive care unit stay (6 vs. 3 days, P = .051)
      than patients receiving 140 g or less. No correlation with risk of acute
      rejection was seen with albumin or tacrolimus. Conclusion-Albumin supplementation
      among liver transplant recipients was associated with a significant risk for
      cardiovascular complications and overall number of complications regardless of
      APACHE III score. Future prospective studies are needed to further define the
      potential risk for complications in this patient population.

PMID- 17007154
TI  - Nonadherence with immunosuppressive drugs: U.S. compared with European kidney
      transplant recipients.
AB  - BACKGROUND: System factors increasingly are suggested as important yet
      understudied correlates of nonadherence. OBJECTIVE: To explore the relationship
      between healthcare system and prevalence of nonadherence with immunosuppressive
      regimen by studying variation in nonadherence between European and US kidney
      transplant recipients and as well as nonadherence in European countries. METHODS:
      We performed a secondary data analysis on data collected in 3 independent cross
      sectional studies using comparable methodology including patients from the United
      States, the Netherlands, Belgium, and Switzerland. Nonadherence was measured
      using 1 item of the Siegal questionnaire. Patients were categorized as
      nonadherent if they reported missing a dose of immunosuppression in the last 4
      weeks. Analyses were performed by multiple mixed logistic regression, with center
      as a random effect and clinical and demographical differences between groups as
      fixed effects. RESULTS: 1563 U.S. and 614 European patients from 3 different
      countries (Belgium [n=187], the Netherlands [n=85], and Switzerland [n=342]) were
      included. Prevalence of nonadherence in the United States and Europe was 19.3%
      and 13.2.%, respectively. This higher nonadherence in US patients was confirmed
      in a multiple logistic regression analysis (OR = 1.78; 95% CI, 1.10-2.89).
      Nonadherence differed between Belgium (16%) and the Netherlands (14.1%) (OR =
      0.27; 95% CI, 0.09-0.80) and between Belgium and Switzerland (11.4%; OR = 0.17;
      95% CI, 0.0-0.42). CONCLUSION: This is the first study showing differences in
      prevalence of nonadherence between European and US patients and among European
      patients. Further research should aim at unraveling the dynamics explaining these
      differences.

PMID- 17007156
TI  - Advance care planning after lung transplantation: a case of missed opportunities.
AB  - After lung transplantation, recipients are regularly evaluated by the transplant
      team and often require multiple hospitalizations. The primary focus of care
      during this time is on detecting and treating complications and may not
      necessarily include advance care planning discussions. This focus may leave
      clinicians unaware of the recipient's treatment preferences and place a burden on
      families trying to decide whether to undergo or forgo life-sustaining treatment
      when the recipient's medical condition deteriorates. We report the case of a
      woman with bronchiolitis obliterans who was admitted to the transplant center 37
      times and died in the intensive care unit. Although progressive deterioration of
      her medical condition was well documented, her medical records revealed no
      evidence of advance care planning discussions with the patient and family.
      Incorporating timely advance care planning and integrating palliative care in the
      ongoing posttransplant clinical management may benefit patients, families, and
      clinicians as recipients approach the final stage of their illness.

PMID- 17007155
TI  - Relationship between coping and depression in heart transplant candidates and
      their spouses.
AB  - CONTEXT: Survival rates for heart transplantation are encouraging, but the
      pretransplant period can be extremely stressful for patients and their spouses.
      Although a relationship between patients' depression levels and the coping
      strategies employed by their spouses has been demonstrated, this association has
      not been examined in heart transplant candidates and their spouses. Depression in
      this group of patients is important because heart transplant patients with
      preoperative depression have been found to have a higher mortality rate after
      transplantation. OBJECTIVE: To determine if a relationship exists between spousal
      coping strategies and heart transplant candidates' depression. METHODS: A
      descriptive, exploratory pilot study. PARTICIPANTS: Twenty-two individuals with
      end-stage heart disease who were undergoing an inpatient evaluation for heart
      transplantation, plus their spouses. Design-Heart transplant candidates were
      assessed via the Structured Interview Guide for the Hamilton Depression Scale.
      Spouses completed the COPE Inventory and the Center for Epidemiological Studies
      Depression Scale. RESULTS: Spousal behavioral disengagement was positively
      associated with heart transplant candidates' depression. CONCLUSIONS: Heart
      transplant candidate depression may follow spousal disengagement, or, conversely,
      a spouse may disengage in response to the patient becoming depressed.
      Identification during the pretransplant evaluation of those spouses who cope
      using behavioral disengagement might be a first step in the process of assessment
      and intervention. Clinical interventions may need to focus on the spouse as well
      as on the transplant candidate.

PMID- 17007157
TI  - Alternative therapy use in liver transplant recipients.
AB  - BACKGROUND: The extent of use of alternative therapies and the psychosocial
      variables predictive of their use have not been well defined in liver transplant
      recipients. OBJECTIVE: To determine types of alternative therapies used by liver
      transplant recipients and to assess psychosocial, behavioral, and quality of life
      variables associated with the use of alternative therapies in these patients.
      METHODS: Assessment of types of alternative therapies used, demographic
      characteristics, satisfaction with social support, coping styles, sense of
      personal control (mastery), quality of life, and health beliefs in 32 liver
      transplant recipients. RESULTS: Overall, 34.4% of the liver transplant recipients
      used a form of alternative therapy. Herbal products were used by 45% of the
      alternative therapy users and included milk thistle (silymarin), eclipta, and
      green beet leaf-all considered "hepatic tonics". Alternative therapy users tended
      to have greater problem-focused coping skills than nonusers (P = .08). Nineteen
      percent of the patients incurred annual out-of-pocket expense of at least dollars
      100 for alternative therapies. Patients incurring out-of-pocket expenses reported
      better overall health (P = .02), were more likely to be employed (P = .025), and
      had higher mastery scores (P = .01). CONCLUSIONS: Use of alternative therapies is
      common after liver transplantation. Herbal products used by liver transplant
      recipients are disease specific; that is, they claim to promote liver health.

PMID- 17007158
TI  - Lifestyle and health status differ over time in long-term heart transplant
      recipients.
AB  - OBJECTIVE: To describe differences in lifestyle and health status across 5 post
      transplant periods. METHODS: The sample consisted of 126 heart transplant
      recipients (87% men) grouped by time after transplantation: group 1, 12 to 24
      months (n= 13); group 2, 25 to 48 months (n= 19); group 3, 49 to 72 months
      (n=24); group 4, 72 to 96 months (n=27); and group 5, > or =97 months (n=43).
      Data were obtained using demographic and health status evaluation forms and the
      Lifestyle Profile-II, which measures physical activity, nutrition, health
      responsibility, interpersonal relationships, stress management, and spiritual
      growth. RESULTS: Most often reported lifestyle attributes were spiritual growth
      and interpersonal relationships. Least often reported was physical activity.
      Pairwise comparisons revealed that groups 3 (chi2 = 16.4; SD = 4.8; P = .03) and
      4 (chi2 = 16.6; SD= 5.8; P = .04) had lower physical activity than group 2 (chi2
      = 21.3; SD = 5.2). Health status evaluation revealed that there were no group
      differences in systolic (P = .46) or diastolic (P = .77) blood pressure. Although
      creatinine was elevated, there were no group differences (P = .86). High-density
      lipoprotein was higher than 42 mg/dL in all groups, but there were differences
      across groups in low-density lipoprotein (P = .003). Groups 1 (chi2 = 139.2; SD =
      38.5) and 2 (chi2 = 141.0; SD = 47.8) were different than group 5 (chi2 = 112.9;
      SD = 36.1; P = .05). There were group differences in cholesterol (P = .002), with
      lower levels in groups 4 (chi2 = 190.5; SD= 38.6) and 5 (chi2 = 186.3; SD = 37.7)
      as compared to group 2 (chi2 = 230.8; SD = 66.5). CONCLUSIONS: Identifying
      posttransplant periods in which healthy behaviors and health status may be
      vulnerable to decline is important for providing ongoing education and
      psychological support to transplant recipients who manage a complex regimen.

PMID- 17007159
TI  - Acanthosis nigricans following single lung transplantation: a case report.
AB  - Acanthosis nigricans was observed 3 months after single lung transplantation in a
      51-year-old African American woman with idiopathic pulmonary fibrosis. The
      patient had no endocrinological abnormalities and was not taking any medications
      known to cause acanthosis nigricans; extensive investigation did not reveal an
      underlying malignant process. Because acanthosis nigricans may occur as a
      paraneoplastic phenomenon, it is important to rule out an underlying malignancy.
      This is especially important in solid-organ transplant recipients receiving
      chronic immunosuppressive therapy.

PMID- 17007160
TI  - Managing the kidney waiting list.
AB  - Candidates on the kidney transplant list wait for longer periods and have
      increasing numbers of comorbid conditions. To ensure that these candidates are
      acceptable for transplantation when an organ becomes available, physical,
      psychosocial, and financial strategies are essential. The authors surveyed 68
      transplant centers to determine current practices. Eighteen percent of centers
      did not reevaluate candidates. Other programs used time on the list, disease,
      age, or a combination of these factors as evaluation criteria. Initial cardiac
      evaluation was relied upon by 51.4% of centers, with varying criteria used to
      determine status. Social work evaluation was done by 42.6% of centers, usually
      annually. Annual financial reevaluation was performed in 57.4%. Data support
      reviewing candidates, especially those with diabetes, those who have been
      receiving dialysis for a long time, and those older than 60 years. The dedication
      of one coordinator to manage waitlisted candidates using age, diagnosis, and time
      receiving dialysis was effective in this study.

PMID- 17007161
TI  - Providing support to families considering the option of organ donation: an
      innovative training method.
AB  - Families must make decisions about organ donation for a loved one during
      intensely emotional circumstances in the hospital, where support from others is
      crucial to their coping. Research about families' experiences during the decision
      making process regarding donating their loved ones' organs has shown that quality
      of hospital care and receiving psychosocial support are important factors
      influencing their decision. Typically, a donation coordinator from the local
      organ procurement organization approaches the family about the option of
      donation, whereas the role of medical and nursing staff is to convey diagnostic
      and prognostic information to the family. Currently, no requirement is in place
      for training of professional staff in communication skills for approaching and
      interacting with families about organ donation. This article discusses a
      simulated training method in empathic communication used for supporting families
      who are approached about organ donation. This innovative method can be adapted to
      and should be tested with professional audiences.

PMID- 17007162
TI  - Design and evaluation of a workplace intervention to promote organ donation.
AB  - BACKGROUND: A number of efforts have been made to improve rates of deceased organ
      donation. However, few have been specifically designed for implementation in the
      workplace. OBJECTIVES: To design and evaluate a workplace intervention to
      increase documentation of intention to be posthumous organ donors, communication
      of donation intention to families, and family members' documentation of their
      donation intentions. METHODS: The study was a randomized controlled trial of
      corporate employees. Within each corporation, worksites were randomized to a
      control condition or 1 of 2 educational interventions. Measures included baseline
      and 1-month postintervention measures of stage of organ donation intention, stage
      of family notification, and family members' organ donation intention. RESULTS:
      Across 12 corporations, 40 worksites with a total of 754 participants were
      randomized. At 1-month follow-up, 495 participants (66%) completed a
      posttreatment questionnaire. The percentage of participants who signed organ
      donor cards increased in the 2 intervention groups (29%, P < .001, and 31%, P <
      .002) but not in the control group (17%, P = .454). The percentage who discussed
      their donation intentions with family members increased significantly across all
      3 arms (39%-47%, P < .001). The mean percentage of participants' family members
      who signed organ donor cards increased by 14% in the control group (P = .016) and
      by 17% in the 2 intervention groups (P < .001). CONCLUSIONS: Educational
      interventions in the corporate workplace setting can be effective in increasing
      organ donation intention, family notification, and recruitment of family members
      as potential organ donors.

PMID- 17007164
TI  - Maximize Medicare risk scores and watch revenue soar.

PMID- 17007163
TI  - Intention to register as organ donors: a survey of adolescents.
AB  - BACKGROUND: Little is known about factors that influence the intention of
      adolescents to register as organ donors. The identification of such factors has
      important implications for the development and implementation of educational
      programs and subsequent donor registration rates. OBJECTIVE: To determine whether
      adolescents with an expressed commitment to becoming organ donor registrants
      differ significantly from nondonors on sociodemographic characteristics and
      factors influencing their decision. PARTICIPANTS: Four hundred forty-five
      adolescents visiting a Department of Motor Vehicles office for a permit or
      license (n=153) or attending a driver's education course (n=292) completed a
      semistructured interview and questionnaire. RESULTS: Female (52.6%) and white
      (55.8%) adolescents were more likely to have favorable donation intentions
      relative to male (45.6%) and nonwhite (39.0%) adolescents (chi2 = 7.5, P = .02,
      and chi2 = 19.7, P = .003, respectively). Those with favorable donation
      intentions also endorsed significantly more positive factors (benevolence, need
      awareness, existentialism) as being more important in their decision. Adolescents
      who did not want to donate (58.7%) and those who were undecided (23.1%) were less
      likely to have discussed their decision with parents than were those who wanted
      to donate (67.7%, chi2 = 63.6, P = .0001). Finally, providing adolescents with a
      free driver's license in exchange for organ donor registration would have the
      greatest impact on registering undecided adolescents (29.8%, chi2 = 33.2, P =
      .0001). CONCLUSIONS: There is a pressing need for more systematic and culturally
      sensitive organ donation education directed toward adolescents, and the
      Department of Motor Vehicles and driver's education courses may be appropriate
      venues. An educational program from the U.S. Department of Health and Human
      Services, Decision: Donation, could be used in this context.

PMID- 17007165
TI  - Arizona still a model for capitated Medicaid programs.

PMID- 17007166
TI  - Priorities of MCOs, physicians differ in managing costs of care.

PMID- 17007167
TI  - Therapeutic potential of cell therapy for cardiac regeneration.

PMID- 17007168
TI  - Acute aortic dissection in children and adolescents: diagnostic and after-event
      follow-up obligation to the patient and family.
AB  - Acute aortic dissection in childhood and adolescence is a rare but life
      threatening condition with many known risk factors, most of which are heritable.
      The importance of determining the presence of any predisposing disorders is
      stressed, since all close relatives can then be screened for any such inherited
      trait that would make them at risk for a similar catastrophic event. Even with no
      obvious predisposing disorder, it may still be prudent to evaluate close kin for
      the presence of aortic root dilatation, since some genetic disorders have no
      manifestation other than acute aortic dissection secondary to aortic medial
      pathology. Close monitoring for at-risk family members, including the index
      patient, may need to be a life-long process.

PMID- 17007169
TI  - Difficulties in maintaining potassium homeostasis in patients with heart failure.
AB  - Potassium (K) concentration plays a significant role in cell metabolism and
      membrane excitability. The imbalance of serum potassium is important because it
      can lead to life-threatening events. Potassium balance may be lost both through
      the neurohormonal mechanisms involved in cardiovascular diseases and through the
      drugs used in the treatment of this illness. Avoiding both hypo- and hyperkalemia
      is beneficial in several cardiovascular diseases, especially heart failure.
      Electrolyte abnormalities are frequently seen complications in subjects with
      heart failure. Malignant ventricular arrhythmias and sudden cardiac death are
      particularly feared complications in K+ instability.

PMID- 17007170
TI  - The effect of a six-week program of yoga and meditation on brachial artery
      reactivity: do psychosocial interventions affect vascular tone?
AB  - BACKGROUND: Chronic stress is estimated to increase the risk of cardiovascular
      (CV) events two-fold. Although stress reduction has been linked to a reduction in
      CV events, little is known regarding its exact mechanism of benefit. HYPOTHESIS:
      Yoga and meditation will improve parameters of endothelial function. METHODS: We
      examined the effects of yoga and meditation on hemodynamic and laboratory
      parameters as well as on endothelial function in a 6-week pilot study. Systolic
      and diastolic blood pressures, heart rate, body mass index (BMI), fasting
      glucose, lipids, hs C-reactive protein (CRP), and endothelial function (as
      assessed by brachial artery reactivity) were all studied at baseline and after 6
      weeks of yoga practice. RESULTS: A course in yoga and meditation was given to the
      subjects for 1.5 h three times weekly for 6 weeks and subjects were instructed to
      continue their efforts at home. This prospective cohort study included 33
      subjects (mean age 55 +/- 11 years) both with (30%) and without (70%) established
      coronary artery disease (CAD). There were significant reductions in blood
      pressure, heart rate, and BMI in the total cohort with yoga. None of the
      laboratory parameters changed significantly with yoga. For the total cohort there
      was no significant improvement in endothelial-dependent vasodilatation with yoga
      training and meditation compared with baseline (16.7% relative improvement from
      7.2-8.4%; p = 0.3). In the group with CAD, endothelial-dependent vasodilatation
      improved 69% with yoga training (6.38-10.78%; p = 0.09). CONCLUSION: Yoga and
      meditation appear to improve endothelial function in subjects with CAD.

PMID- 17007171
TI  - Is there a better way to predict death using heart rate recovery?
AB  - BACKGROUND: Heart rate recovery (HRR) during exercise testing is an independent
      predictor of prognosis. The relative predictive power of computational analysis
      of HRR as a function of resting and maximum heart rate (HR) compared with direct
      measurement of the drop in HR has not been determined. HYPOTHESIS: We aimed to
      improve on the prognostic value of HRR by the use of mathematical representations
      of HRR kinetics. METHODS: In all, 2,193 patients who underwent exercise testing,
      coronary angiography, and clinical evaluation were followed up for 10.2 +/- 3.6
      years. Mathematical functions were used to model HRR as a function of resting
      (HR(Rest)), maximum HR (HR(Peak)) and time (t): (a) HRR= HR(Rest) + (HR(peak) -
      HR(Rest)) X e(-kt) and (b) HRR= HR(Rest) + (HR(peak) - HR(Rest)) e(-kt2) RESULTS:
      Equation (b) provided the best fit of the recovery HR curve. An abnormal HRR at 2
      min was a better predictor of mortality than HRR at 1, 3, or 5 min. At 2 min, HRR
      also predicted mortality better than computational models of HRR, relating HRR as
      a function of maximum and resting HRs. After adjusting for univariately
      significant predictors of mortality, HRR, age, exercise capacity, and maximum HR
      were chosen in order as the best predictors of mortality. CONCLUSION: Even though
      the computational models of HRR and the determination of HRR at different time
      intervals were significant predictors of mortality, the simple discrete measure
      of HRR at 2 min was the best predictor of mortality. At 2 min, HRR outperformed
      age, METs, and maximum exercise HR in predicting all-cause mortality.

PMID- 17007172
TI  - Prognostic value of serum biomarkers in association with TIMI risk score for
      acute coronary syndromes.
AB  - BACKGROUND: Markers of neurohormonal activation and inflammation play a pivotal
      role in non-ST-elevation acute coronary syndromes (NSTE-ACS). HYPOTHESIS: We
      hypothesized that other biochemical markers could add prognostic value on
      Thrombolysis In Myocardial Infarction (TIMI) risk score to predict major
      cardiovascular events in patients with NSTE-ACS. METHODS: In a cohort of 172
      consecutive patients with NSTE-ACS, TIMI score was assessed in the first 24 h,
      and blood samples were collected for measurement of N-terminal pro-brain
      natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein, CD40
      ligand, and creatinine. Major clinical outcomes (death and cardiovascular
      hospitalization) were accessed at 30 days and 6 months. Multivariate logistic
      regression was applied to identify markers significantly associated with outcomes
      and, based on individual coefficients, an expanded score was developed. RESULTS:
      Of 172 patients, 42% had acute myocardial infarction. The unadjusted 30-day event
      rate increased with age (odds ratio [OR] = 1.03; 95% confidence interval [CI]
      1.00-1.06), creatinine (OR = 2.4; 1.4-4.1), TIMI score (OR = 1.6; 1.2-2.2),
      troponin I (OR = 3.4; 1.5-7.7), total CK (OR = 2.7; 1.2-6.1), and NT-proBNP (OR =
      2.9; 1.3-6.3) levels. In multivariate analysis, TIMI risk score, creatinine, and
      NT-proBNP remained associated with worse prognosis. Multimarker Expanded TIMI
      Risk Score [TIMI score + (2 X creatinine [in mg/dl]) + (3, if NT-proBNP > 400
      pg/ml)] showed good accuracy for 30-day (c statistic 0.77; p < 0.001) and 6-month
      outcomes (c statistic 0.75; p < 0.001). The 30-day event rates according to
      tertiles of expanded score were 7, 26, and 75%, respectively (p < 0.01).
      CONCLUSION: In NSTE-ACS, baseline levels of NT-proBNP and creatinine are
      independently related to cardiovascular events. Both markers combined with TIMI
      risk score provide a better risk stratification than either test alone.

PMID- 17007173
TI  - Respiratory changes in the pulse-oximetry waveform associated with pericardial
      tamponade.
AB  - BACKGROUND: Timely identification of hemodynamic compromise in patients with
      acute pericardial effusion and tamponade is critical in patient management.
      Respiratory variability in pulse-oximetry waveforms has been correlated with
      pulsus paradoxus, but has not been reported with cardiac tamponade in adult
      patients. HYPOTHESIS: This study describes changes in respiratory variability in
      pulse-oximetry waveform pre and post pericardiocentesis in patients with
      hemodynamically significant pericardial effusions. METHODS: A single-center,
      catheterization laboratory hemodynamic database was reviewed for all patients who
      underwent pericardiocentesis for clinically suspected tamponade and had
      continuous digital pulse-oximetry, electrocardiographic, and respiration
      waveforms recorded during the procedure. Phasic respiratory changes in pulse
      oximetry waveform amplitude (maxima-minima) were expressed as an
      expiratory/inspiratory ratio and compared pre and post pericardiocentesis.
      RESULTS: The study population consisted of 12 patients (6 men:6 women, age 60 +/-
      10 years) with pericardial effusion documented by echocardiography on the day of
      pericardiocentesis. Phasic respiratory variability in the pulse-oximetry waveform
      was evident in all patients prior to aspiration (respiratory ratio = 1.9 +/-
      0.5). Following pericardiocentesis (aspirated volume: 650 +/- 300 ml), the
      respiratory ratio decreased in all patients (1.2 +/- 0. 1, p = 0.001). Receiver
      operator characteristic curve analysis suggests that pulse-oximetry respiratory
      ratios > or = 1.5 should raise suspicion of hemodynamic compromise in high-risk
      populations. CONCLUSIONS: Pulse-oximetry is a commonly used tool for monitoring
      critically ill patients. The present study suggests that increased respiratory
      variability in the pulse-oximetry waveform should raise suspicion for hemodynamic
      compromise in patients at risk for pericardial effusion.

PMID- 17007174
TI  - The value of using the entire New York Heart Association's classification of
      heart and vascular disease.
AB  - The New York Heart Association functional classification is commonly used because
      the value of its determination is generally appreciated. The other four parts of
      the classification (etiology, anatomy, physiology, and objective assessment) are
      used less often. The purpose of this paper is to point out the value of using the
      entire New York Heart Association classification.

PMID- 17007176
TI  - Images in cardiology: subaortic stenosis caused by left ventricular outflow tract
      lipoma.

PMID- 17007175
TI  - Transient global left ventricular dysfunction in a localized myocardial
      infarction related to occlusion of the distal left anterior descending artery.
AB  - In some patients with acute myocardial infarction (MI), wall motion in the
      noninfarcted area declines globally despite localized myocardial damage. In most,
      an infarct-related lesion is the proximal part of the left anterior descending
      artery (LAD). Previous studies have reported that hypokinesis of remote
      myocardium may be related to multivessel disease, impaired coronary flow, or
      coronary flow reserve in nonculprit arteries. This report describes the case of a
      53-year-old man who presented with severe global left ventricular (LV)
      dysfunction after an acute MI associated with distal LAD occlusion. Follow-up
      echocardiographic examination revealed nearly normalized LV function 5 days after
      the episode. We discuss a plausible mechanism of dysfunction of noninfarcted
      myocardium.

PMID- 17007177
TI  - Images in cardiology: macroscopic T-wave alternans.

PMID- 17007178
TI  - Images in cardiology: diffuse aneurysmal disease.

PMID- 17007179
TI  - William Thornton Mustard.

PMID- 17007180
TI  - Pregnancy and prosthetic atrioventricular valve thrombosis.

PMID- 17007181
TI  - [Pathophysiology of cholesteatoma].
AB  - OBJECTIVE: To describe the development of cholesteatoma using current knowledge.
      METHOD: Review of the literature. RESULTS: Cholesteatoma describes a mass of
      keratin (skin) in the middle ear which consists of a perimatrix and matrix. There
      are at least three kinds of cholesteatoma in the middle ear one resulting from
      invagination (retraction's pocket), another from migration and the last one from
      congenital inclusion. Cholesteatoma needs three successive inflammatory phases,
      the first leading to a retraction pocket, the second leading to pathology of the
      epidermis and of the floor of the external auditory canal and the third is the
      actual phase of cholesteatoma with invasion and middle ear auto-destruction with
      bone resorption. In this last phase, many factors play a role, collagenasis,
      osteoclats, cytokines, NO, bacteria and their biofilm and rupture of the
      retraction pocket. CONCLUSION: Cholesteatoma is an inflammatory disease of the
      ear caracterised by bone resorption. Current research is starting to appreciate
      the important role the immune system plays in the pathophysiology of
      cholesteatoma.

PMID- 17007182
TI  - [Revision ossiculoplasty: anatomical and functional results].
AB  - OBJECTIVES: To analyse the anatomical and functional results after second-look
      ossiculoplasty using Titanium (TI) and Hydroxyapatite (HA) prosthesis and to
      study the prognostic factors for good functional results. PATIENTS AND METHODS:
      Forty nine patients (19 men and 30 women) with an average age of 36 years were
      included in this study. The patients presented with anatomical and/or functional
      failures after a first ossiculoplasty and had a second-look intervention. The
      status of the first prosthesis and also the anatomical status of the middle ear
      and the remaining ossicular chain were described intra operatively. The
      functional and anatomical results were assessed 2 months after the second
      ossiculoplasty and during the most recent out patient clinic. Postoperative air
      conduction gain (ACG) and air bone gap (ABG) were calculated in average values
      using four frequencies: 0.5, 1, 2 and 4 kHz. The variables used in statistical
      analysis were the following: Tympanic membrane and preoperative middle ear
      status, the type of prosthesis (partial or total) and its material (TI and HA).
      RESULTS: The average time to second-look operation was 18 months. The
      postoperative ABG did not show any significant statistic improvement and in
      several patients auditory function deteriorated in the operated ear The
      predictive factors for good functional results were: The integrity of the
      tympanic membrane, chronic otitis media without cholesteatoma, total prosthesis
      and HA prosthesis. If three of these factors were present, the postoperative ABG
      would always be less than 20 dB. CONCLUSION: When selecting patients for second
      look ossibuloplasty it is important to understand the predictive facctors for
      good results. This will allow a full discussion of options, risks and morbidity
      with the patient.

PMID- 17007183
TI  - [Far-advanced otosclerosis].
AB  - OBJECTIVES: The aim of this study was to report a series of patients with far
      advanced otosclerosis who were unable to benefit from hearing aids. Among
      patients with profound hearing loss, it is particularly useful to diagnose far
      advanced otosclerosis even if relatively rare, because stapes surgery can improve
      hearing to a level allowing conventional hearing aid use (sometime the only
      choice before cochlear implant). MATERIAL AND METHODS: We retrospectively
      reviewed the charts of 7 patients (9 operated ears) in order to highlight
      diagnostic criteria, surgical indications and results of stapes surgery
      (stapedectomy or stapedotomy). RESULTS: Diagnosis of far-advanced otosclerosis
      was based on clinical presentation, course of hearing loss, positive family
      history of otosclerosis, and results of CT scan which was helpful in all the
      cases. Obliterative otosclerosis was found in 55% of the cases. Success of stapes
      surgery was observed in 89%, with no significant difference between stapedectomy
      or stapedotomy. CONCLUSION: Although rare, far-advanced otosclerosis must be
      diagnosed because patients can benefit from stapes surgery (and subsequently
      fitting of appropriate hearing aids).

PMID- 17007184
TI  - Comparison of radical (nasalisation) and functional ethmoidectomy in patients
      with severe sinonasal polyposis. A retrospective study.
AB  - OBJECTIVE: To compare the 5-year outcomes of two endoscopic surgical approaches
      for diffuse and severe nasal polyposis. STUDY DESIGN: A natural experimental
      situation gave us the opportunity to compare the results 5 years after radical
      ethmoidectomy (nasalisation) (n= 39), and functional ethmoidectomy (n= 37). The
      two surgical procedures were performed by two different surgeons on 76
      consecutive patients. There was no random assignment for this retrospective
      study. METHODS: Five years after surgery, the criteria for comparison were 1)
      functional results based on a questionnaire using visual analogue scales in
      patients free of revision surgery; 2) endoscopic and CT-scan assessments of
      anatomical results. The CT-scans were blinded and randomized, and opacities were
      measured using a computerized model; 3) the recurrence rate of nasal polyps.
      RESULTS: Five years after surgery, the overall nasal functional benefit was
      scored 8.41 +/- 0.40 (mean +/- SEM) after nasalisation, and 5.69 +/- 0.83 after
      ethmoidectomy P= 0.002) in patients free of revision surgery. The endoscopic
      appearance of the mucosa was methodically scored according to a pre-defined
      scale. Results were significantly better in the nasalisation group (6.03 +/- 0.7
      versus 3.27 +/- 1.0, P= 0.02). A good correlation was found between the
      endoscopic and CT-scan scores (r= -0.78, P= 0.0001 for nasalisation, and r= 
      0.65, P= 0.001 for ethmoidectomy). The total recurrence rate was 22.7% in the
      nasalisation group, and 58.3% in the ethmoidectomy group (chi2= 10.41, P< 0.01).
      CONCLUSION: Our study suggests that in the treatment of nasal polyposis complete
      ethmoidectomy leads to better long term results than incomplete ethmoidectomy.

PMID- 17007185
TI  - [Early PTH assay after total thyroidectomy: predictive factor for post operative
      hypocalcemia?].
AB  - OBJECTIVES: Hypocalcemia is the most common complication of total thyroidectomy.
      During surgery the blood supply to preserved parathyroid glands may be
      compromised, monitoring for post operative hypocalcemia is often the primary
      reason patients remain in hospital. The aim of this prospective study was to
      evaluate the role of early parathyroid hormone (PTH) assay for predicting
      thyroidectomy-related hypocalcemia. MATERIAL AND METHODS: 62 patients underwent
      total thyroidectomy between November 2004 and April 2005 in our institution.
      Quick PTH assay was performed 1 hour post thyroidectomy. Based on the result (PTH
      > or <16 pg/mL) the patients were separated into two groups. Serum calcium levels
      and ionised fractions were determined 24, 48 and 72 hours after surgery. Post
      operative hypocalcemia was defined as calcium levels <2.00 mmol/L and/or ionised
      calcium levels <1.00 mmol/L. RESULTS: In 16 cases hypocalcemia occurred in the
      first 72 hours (25.8 %). In all of these cases, PTH measured 1 hour after
      thyroidectomy was < or = 16 pg/mL. All patients with PTH >16 pg/mL one hour after
      the operation remained normocalcemic. Of the 29 patients with a PTH < or =16
      pg/mL at one hour post surgery, 13 remained normocalcemic. Quick PTH measurements
      which were < or =16 pg/mL post thyroidectomy were an excellent predictive factor
      of hypocalcemia with a sensibility of 100%, a specificity of 71.7%, a positive
      predictive value of 55.2% and a negative predictive value of 100%. CONCLUSION:
      PTH measurement 1 hour post thyroidectomy can potentially highlight those
      patients at risk of hypocalcemia. This would allow more efficient replacement
      therapy with calcium and vitamin D thus avoiding complications and reducing total
      hospital stay.

PMID- 17007186
TI  - [Amphicrine adenoma of the middle ear: three cases reports and a review of the
      literature].
AB  - Amphicrine adenoma is an extremely rare tumor of the middle ear. We report three
      cases obtained over a twenty year period. THE AIM OF THIS STUDY: is to discuss
      our clinical cases and review the literature. MATERIALS AND METHODS: Three cases
      of middle ear amphicrine tumour were reviewed. RESULTS: During a 10 year period
      (1986-2006) three cases of middle ear amphicrine tumour were treated at our unit
      (2 male, 1 female). The presenting complaint was hearing loss in all 3 cases.
      Amphicrine adenoma is diagnosed by an immuno-histological examination of
      pathological specimens. Differential diagnosis can be difficult and one
      individual was initially treated as an adenocarcinoma by radiotherapy. This
      patient succumbed to cerebral mycosis two years post-radiotherapy. The other two
      patients have no evidence of recurrence eight and nine years post treatment.
      CONCLUSION: Historically, differential diagnosis between amphicrine adenoma and
      adenocarcinoma of the middle ear has been very difficult. Carcinoid tumour is
      considered to be a more agressive form of amphicrine adenoma. Tumour progression
      is through loco regional invasion. Complete excision by surgical management with
      long term follow up is the treatment of choice.

PMID- 17007187
TI  - [Dehiscence of the anterior semicircular canal and otosclerosis: a case report].
AB  - The dehiscence of the anterior semicircular canal is a new clinical entity, it is
      necessary to consider this when a gusher occurs during stapedial surgery. CASE
      REPORT: We report a rare case of dehiscence of the anterior canal associated with
      otosclerosis. This was revealed by a gusher during the initial stapedectomy. At 3
      months, an obliteration of the dehiscence was necessary by middle cranial fossa
      approach (persistant vestibular symptoms), seven months later. Revision stapedial
      surgery resulted in complete closure of the air-bone-gap. CONCLUSION: High
      resolution CT scans of the temporal bone are the key to diagnosis. It is
      necessary to appreciate this pathology with advances in canal and vestibular
      surgery.

PMID- 17007188
TI  - [Association of Bezold's abscess and sigmoid sinus thrombosis. A case report].
AB  - Bezold's abscess and sigmoid sinus thrombosis are both classic complications of
      otitis media. However, since the introduction of antibiotics both have become
      very rare. Very few cases of these complications occurring concomitantly have
      been reported. We describe the clinical case of a 45 year old male with a 10 year
      history of neglected right ear cholesteatoma. The patient presented to our
      department with a 10 day history of purulent right otorrhea, otalgia, increasing
      headach, pyrexia and suppurating right parapharyngeal mass. CT scan confirmed
      right middle ear cholesteatoma associated with ipsilateral Bezold abscess and and
      sigmoid sinus thrombosis. Treatment was by mastoidectomy, broad spectrum
      intravenous antibiotics and anticoagulation. The patient made a full
      uncomplicated recovery. The association between chronic middle ear disease,
      sigmoid sinus thrombosis and Bezold abscess are discussed.

PMID- 17007189
TI  - [Posterior cranial fossa abscess secondary to cholesteatoma].
AB  - OBJECTIVE: The intra cranial complications of chronic ear disease continue to
      pose a challenge in Senegal, despite advances in anti microbial therapy.
      Posterior cranial fossa abscesses are rare and continue to be associated with
      significant morbidity and mortality rates. We describe the presentation and
      management of a large cerebellar abscess secondary to cholesteatoma. METHODS AND
      RESULTS: A 11-year-old female presented with an inflammed fluctuant swelling of
      the right temporal region with ipsilateral otorrhoea. Examination demonstrated an
      auto atticotomy, large marginal perforation of the tympanic membrane associated
      with polyp. A diagnosis of otomastoiditis secondary to cholesteatoma was made.
      The abscess of the right temporal region was incised and drained and the patient
      was commenced on broad spectrum antibiotics. However the patients clinical status
      did not improve and there was a deterioration in her neurological status. CT
      brain and temporal bones demonstrated a large abscess in the cerebellum. 30 CC of
      pus were drained through a posterior fossa burr hole by the neurosurgeons. A
      radical mastoidectomy for extensive cholesteatoma of the right ear was
      subsequently carried out when the patients condition improved. CONCLUSION:
      Cerebellar abscess is a life threathning condition. In the presence of
      complicated chronic ear disease, clinical suspicion must be high as early
      symptoms and signs may be misleading. A low threshold for the performance of
      brain imagining will aid early diagnosis and allow prompt definitive treatment.

PMID- 17007190
TI  - [Sphenoid sinus mucocele of unusual aetiology and location].
AB  - Mucoceles of the sphenoid sinnus are rare. 140 cases have been reported in the
      literature. PURPOSES: We review a case and discuss: 1) pathophysiology and
      diagnosis of mucoceles; 2) etiologies, anatomical variants, clinical
      manifestations and treatment of sphenoidal mucoceles. MATERIAL AND METHOD: Case
      report and literature review. CASE REPORT: An 18-year-old female, with no past
      medical history was hospitalized for right fluctuating monocular blindness. MRI
      and CT scan facilitated the diagnosis of right clinoid mucocele with compression
      of the optic nerve. Imagery also revealed fibrous dysplasia of the anterior skull
      base which probably induced the mucocele formation. The mucocele was successfully
      decompressed during endoscopic sinus surgery. Postoperative course was
      unremarkable. At four months post surgery there was no recurrence of
      ophtalmological symptoms. DISCUSSION-CONCLUSION: The pathophysiology of mucoceles
      remains uncertain. Diagnosis is based on imagery (CT scan, RMI). Imagery allows
      accurate location of the mucocele, defines any concomitant pathology and oulines
      important anatomical structures necessary for safe endoscopic sinus surgery. The
      association of fibrous dysplasia and an anterior clinoidal mucocele is
      exceptional. To our knowledge this is the only report in the literature.
      Ophtalmologic symptoms with a risk of blindness require urgent surgical
      treatment. Surgery involves decompression, ideally endoscopically.

PMID- 17007191
TI  - [Giant form of infantile myofibromatosis located on the jaw].
AB  - INTRODUCTION: Infantile myofibromatosis is a rare fibrovascular-like tumour,
      characterized by the development of single or multiple nodular lesions arising
      from cutaneous, subcutaneous, muscular bone or visceral structures, diagnosed
      before 2 years. OBSERVATION: We report a case of infantile myofibromatosis
      located on the jaw, which is unique because of its large size (12 cm), its
      location and its neonatal presentation. It was a voluminous proliferate tumour
      with an ulcerated centre, located on the left jaw. Surgical excision was complete
      and the diagnosis was maded on histological examination. Recovery was
      uncomplicated with no recurrence on follow up. DISCUSSION: Diagnosis of infantile
      myofibromatosis is difficult because of the clinical heterogeneity and the
      histopathological appearance. The histological diagnosis relies on identification
      of two separate components, fascicular myofibroblastic at the periphery and
      hemangiopericytome in the centre. The most freqaent treatment is conservative
      surgical excision, because recurrence rates are low and there is a possibility of
      spontaneous regression. Some authors recommend conservative management of very
      large or multiple lesions particularly if excision will result in significant
      functional or cosmetic morbidity.

PMID- 17007192
TI  - [Papillary thyroid carcinoma metastasis to parapharyngeal lymph nodes: interest
      of the PET scan].
AB  - Thyroid cancer rarely metastasizes to the parapharyngeal space. A inconsistent
      lymphatic drainage pathway is involved, as described by Rouviere. OBJECTIVES: To
      demonstrate the interest of [18 F]-FDG PET in early diagnosis of metastasis and
      in the follow up of the patient. MATERIAL AND METHOD: 40 y.o. male with papillary
      carcinoma who had a secondary parapharyngeal metastasis. The diagnosis of
      recurrence was difficult, as the plasmatic thyglobulin was low, and the iodine
      scan was not informative. In this case, [18 F]-FDG PET-CT was informative (clear
      parapharyngeal fixation) and led to the diagnosis of recurrence. CONCLUSION: It
      appears that 18F FDG PET has a good diagnostic value and that its sensitivity is
      better than CT scan and MRI. Some authors recommend the use of [18 F]-FDG PET and
      scintigraphy with Iodine 131 to screen patients with thyroid cancer recurrences.

PMID- 17007194
TI  - [Granular cell tumours (Abrikossoff's tumour) of the parotid region].
AB  - BACKGROUND: Granular cell tumour (Abrikossoff's tumour) was first described by
      Abrikossoff in 1926. These tumours are rare and usually presents as a solitary
      lesion, located mainly in the subcutaneous tissue of the head and neck, and in
      the oral cavity (tongue). CASE REPORT: We report a rare case of a granular cell
      tumor of the parotid gland, in a 55-year old woman, who was referred with a left
      preauricular mass that had rapidly increased in size over 2 months. There was no
      cervical lymph adenopathy. RMI demonstrated a solitary lesion of the parotid
      gland. Surgical resection was performed. CONCLUSION: We discuss the
      classification, pathophysiology and the treatment of granular cell tumours
      through a review of the literature.

PMID- 17007193
TI  - [Papillary thyroid microcarcinoma presenting as cervical lymph node metastasis.
      Interest of tetrofosmin scintigraphy and lymph node thyroglobulin measurement].
AB  - PURPOSE OF THE STUDY: Thyroid microcarcinoma presenting as cervical lymph node
      metastasis is common and it is associated in most cases with the papillary
      variety. Diagnosis of lymph node metastases from a thyroid microcarcinoma is not
      always easy, because a thyroid nodule may not be palpable. MATERIAL AND METHOD:
      In this work, the authors report two cases of papillary microcarcinoma presenting
      as cervical lymph adenopathy. RESULTS: The diagnosis was made preoperatively by
      Tetrofosmin scintigraphy and thyroglobulin measurement in the lymph node.
      CONCLUSION: Tetrofosmine scintigraphy is a performing exam but with a poor
      specificity. Lymph node thyroglobulin is a simple exam which is very sensitive
      and specific.

PMID- 17007195
TI  - [Primary sub-mandibular gland tumours: experience based on 68 cases].
AB  - Sub-mandibulary gland tumours are less common than tumours of the parotid and
      pose many clinical and therapeutic challengers. OBJECTIVE: We report our
      experience of sub-mandibular tumours and review the literature. PATIENTS AND
      METHODS: Retrospective studies of sub-mandibular gland tumours presenting to our
      department between 1986 and 2000. RESULTS: 68 cases were reviewed comprising 37
      benign and 31 malignant tumours (15 females and 33 males). Average age of patient
      was 46 years and all presented with a sub-mandibular swelling. Clinical suspicion
      of malignancy was associated with symptom of pain, cervical adenopathy, nerve
      palsy, skin and/or bone invasion. CAT Scans were performedd to assess tumour
      extent / invasion. Definitive diagnosis was by complete excision and pathological
      examination. Pleomorphic adenoma (n= 32) were the most frequent benign tumours.
      For malignant lesions (n= 31) the most frequent were: Adenoid cystic carcinoma
      (n= 10), epidermoid carcinoma (n= 5), adenocarcinoma (n= 5), mucoepidermoid
      carcinoma (n= 3), malignant non Hodgkinien lymphoma (n= 5). Treatment was by
      total surgical excision of the submandibular gland for the begnin tumours. For
      the malignant lesions it was associated acording to their extension with other
      anatomical region or in case of adenopathy with neck dissection. Radiotherapy was
      performed in 24 cases and chemotherapy in 10 cases. CONCLUSION: Malignity in sub
      mandibular gland tumours is more frequent than in the parotid gland. Any delay in
      diagnosis or inappropriate management may result in a poor prognosis for the
      patient.

PMID- 17007196
TI  - Interstitial brachytherapy as the sole treatment for tongue metastasis from
      breast carcinoma.
AB  - Breast carcinoma metastasize more frequently to the bone, liver lung and brain as
      compared to other anatomical sites. As such, advanced breast tumours with
      secondaries involving the rarer sites often pose when a therapeutic challenge for
      the clinician to find a good balance between offering the most effective therapy
      and its potential toxicity. We report the first case of tongue metastasis from
      breast cancer that was successfully treated with interstitial brachytherapy,
      resulting in good local control and no severe side effects.

PMID- 17007197
TI  - [Clinical research pays off. Big net profits are to be gained by improved health
      according to an American study].

PMID- 17007198
TI  - [Increasing incidence of early reoperation of dislocation after primary hip
      arthroplasty. An analysis of the national hip arthroplasty registry].

PMID- 17007199
TI  - [The physician-patient-relative meeting--two case reports].

PMID- 17007200
TI  - [Hypereosinophilic syndrome--difficult-to-catch diagnosis. Targeted molecular
      diagnostics and treatment now possible thanks to gene discovery].

PMID- 17007201
TI  - [Four cases of lactic acidosis following metformin treatment].

PMID- 17007202
TI  - [Investigation of scientific fraud. Responsibility of the authorities].

PMID- 17007203
TI  - [Unnecessarily long sick leave caused by the Social Insurance Office and the
      employers].

PMID- 17007204
TI  - [It's possible to increase the number of house calls in primary health care].

PMID- 17007205
TI  - [Students with to spend more time at community health centers].

PMID- 17007206
TI  - [Clinical research must be based on teaming physician and researcher].

PMID- 17007207
TI  - [Homocysteine not yet out of the game!].

PMID- 17007208
TI  - [Physicians' dressing important in the patient-physician encounter].

PMID- 17007209
TI  - Helminths in Mesaspis monticola (Squamata: Anguidae) from Costa Rica, with the
      description of a new species of Entomelas (Nematoda: Rhabdiasidae) and a new
      species of Skrjabinodon (Nematoda: Pharyngodonidae).
AB  - Entomelas duellmani n. sp. (Rhabditida: Rhabdiasidae) from the lungs and
      Skrjabinodon cortagoensis n. sp. (Oxyurida: Pharyngodonidae) from the intestines
      of Mesaspis monticola (Sauria: Anguidae) are described and illustrated. E.
      duellmani is the sixth species assigned to the genus and is the third species
      described from the Western Hemisphere. It is easily separated from other
      neotropical species in the genus by pre-equatorial position of its vulva.
      Skrjabinodon cartagoensis is the 24th species assigned to the genus and differs
      from other neotropical species in the genus by female tail morphology.

PMID- 17007210
TI  - New filarial nematode from Japanese serows (Naemorhedus crispus: Bovidae) close
      to parasites from elephants.
AB  - A new onchocercid species, Loxodontofilaria caprini n. sp. (Filarioidea:
      Nematoda), found in subcutaneous tissues of 37 (33%) of 112 serows (Noemorhedus
      crispus) examined in Japan, is described. The female worm had the characteristics
      of Loxodontofilaria, e.g., the large body size, well-developed esophagus with a
      shallow buccal cavity, and the long tail with three caudal lappets. The male worm
      of the new species, which was first described in the genus, had unequal length of
      spicules, 10 pairs of pre- and post-caudal papillae, and three terminal caudal
      lappets. Deirids were present in both sexes. Among four species of the genus
      loxodontofiloria: one from the hippopotamus and three from the Elepantidae, L.
      caprini n. sp. appears close to L. asiatica Bain, Baker & Chabaud, 1982, a
      subcutaneous parasite of Elephas indicus in Myanmar (Burma). However, L. caprini
      n. sp. is distinct from L. asiatica in that the Japanese female worm has an
      esophagus half as long and the microfilariae also half as long with a coiled
      posterior. The microfilariae were found in the skin of serows. The new parasite
      appears to clearly illustrate a major event in the evolution of onchocercids: the
      host-switching. This might have occurred on the Eurasian continent, where
      elephantids and the lineage of rupicaprines diversified during the Pliocene
      Pleistocene, or in Japan, into which some of these hosts migrated.

PMID- 17007211
TI  - A new species of Hypocristata (Nematoda, Trichostrongyuna, Heligmosomoidea) a
      parasite of Sigmodon hispidus (Cricetidae, Sigmodontinae) from Venezuela.
AB  - Description of Hypocristata tercera n. sp. (Heligmonellidae, Nippostrongylinae) a
      parasite of the small intestine of Sigmodon hispidus (Rodent, Sigmodontinae) from
      Venezuela. Two other species were described in the genus, both from Colombia and
      parasitic in Sigmodontinae. H. thomosomysi Durette-Desset, 1970, a parasite of
      Thomasomys sp. has about the same number of cuticular ridges at mid-body but
      differs by ridges having chitinoid struts, a caudal bursa pattern of type 2-2-1
      (vs 1-3-1). H. anguillula Durette-Desset, 1970, a parasite of Sigmodontomys
      alfari (= Nectomys alfari) has the same caudal bursa pattern (type 1-3-1) but
      differs by the presence of ridges at mid-body in both sexes (absent at that level
      in H. tercera) and by ridges having chitinoid struts in female. This is the first
      report of the genus Hypocristata Durette-Desset, 1971 in Venezuela and in the
      genus Sigmodon (Sigmodontinae).

PMID- 17007212
TI  - Seasonal morphological variations in bird schistosomes.
AB  - The present work is a contribution to the systematics of Bilhorziello and
      Dendritobilharzio. Wildfowl was killed in hunting seasons or found dead in
      Champagne-Ardenne region, France, and autopsied with focus on schistosomes. Seven
      Anas plotyrhynchos (mallards), one Ardeo cinerea (grey heron) and two Cygnus olor
      (mute swans) were parasitized by Bilharziella. One C. olor was parasitized by
      Dendritobilharzia. Depending on season and hosts, various morphological forms of
      Bilharziello suggesting several species were observed. The differences in male
      and female worms concerned the morphology of genital apparatus, the spination on
      suckers, the body size and proportions. However, the comparison of DNA sequences
      led to a conclusion that these forms belonged to one species, Bilharziella
      polonica (Kowalewski, 1895). The morphological features and the body sizes of our
      samples of Dendritobilharzia seemed to differ from the type species of D.
      pulverulenta (Braun, 1901). Nevertheless, molecular analysis confirmed identity.
      We hypothesize that the differences in Bilharziella and Dendritobilharzia might
      be linked to internal host factors (e.g. hormonal levels), and influenced by
      season, host, and worm age. The definition of the genera Bilharziello and
      Dendritobilharzio was amended.

PMID- 17007213
TI  - Three new fleas from Sulawesi, Indonesia (Siphonaptera: Pygiopsyllidae &
      Ceratophyllidae).
AB  - Gryphopsylla maxomydis n. sp. (Pygiopsyllidae), Medwayella rubrisciurae n. sp.
      (Pygiopsyllidae) and Macrostylophora theresae n. sp. (Ceratophyllidae) are
      described from endemic rodents in Sulawesi. Gryphopsylla maxomydis was collected
      from the murids Maxomys musschenbroekii and Paruromys dominator in Central
      Sulawesi (Sulawesi Tengah). However, M. musschenbroekii appears to be the true
      host of this flea because it has spiny pelage and G. maxomydis shows
      morphological adaptations for parasitizing spiny hosts including a remarkable
      "beak-like" structure on the head. This adatation is similar to a beak-like
      structure on the head of Gryphopsyllo hopkinsi (Traub) which parasitizes the
      spiny murid Maxomys whiteheadi in Borneo (Sabah). Medwayella rubrisciurae was
      collected from the large tree squirrel Rubrisciurus rubriventer in Central
      Sulawesi and this represents the first report of this flea genus in Sulawesi.
      Macrostylophora theresce was recorded from the murids Bunomys fratrorum, P.
      dominator and Rattus xanthurus in North Sulawesi (Sulawesi Utara); most other
      members of this flea genus parasitize squirrels in the Oriental and Palaearctic
      zoogeographical regions.

PMID- 17007214
TI  - [A new bird flea from Chile (Siphonaptera: Ceratophyllidae].
AB  - Doasypsyllus (Neomipsyllus) aedon n. sp. is described from specimens obtained
      from Passeriform's nests (Troglodytidae and Furnariidae).

PMID- 17007215
TI  - The sera from individuals suffering from cutaneous leishmaniasis due to
      Leishmania brazilensis present antibodies against parasitic conserved proteins,
      but not their human counterparts.
AB  - Sera from individuals suffering from leishmaniasis have been shown to strongly
      react against conserved proteins from the parasite, such as ribosomal, histones
      and heat-shock proteins. Some of these proteins have also been described as
      immunogenic in several auto-immune syndromes, and the detection of antibodies
      against them is considered to be indicative of disorder of the immune system. In
      this paper, we investigate whether there is any relationship between the
      recognition of some conserved proteins from leishmania braziliensis by
      individuals suffering from cutaneous (CL) and mucocutaneous (MCL) leishmaniasis,
      and the recognition of the human homologues of these antigens found in sufferers
      from autoimmune diseases. Our findings reveal that the immune response generated
      during CL and MCL is elicited specifically by the parasitic histone H1 and Hsp70,
      since the CL and MCL sera do not react against their human counterparts. In
      addition, evidence is presented showing the specific recognition of human
      proteins by the autoimmune sera, showing only a weak cross-reaction with the most
      divergent regions of the parasitic proteins.

PMID- 17007216
TI  - Peridomestic structure, farming activity and triatomine infestation.
AB  - The role of peridomestic structure and farming activity on triatomine infestation
      was studied on two vector species of Chagas disease (Triatoma pseudomaculata and
      T. brasiliensis) in Bahia State, northeastern Brazil. A randomly selected
      population issued from 136 farms was divided into four categories according to
      the householder activity. At regional scale, the dwellings of farmers working on
      degraded land of irrigated farms are less exposed to T. pseudomaculata
      infestation. At premises scale, the farmers and casual workers, who have smaller
      peridomiciles and less cattle, are also less exposed to T. pseudomaculata. The
      association of T. brosiliensis with the most mobile populations (casual workers
      and young breeders) suggests a passive transport of this competitive species.
      Finally, the retired farmers that own large premises and cattle, but have more
      sedentary behavior, are the most exposed to T. pseudomaculata infestation.

PMID- 17007217
TI  - First survey of seasonal abundance and daily activity of Stomoxys spp. (Diptera:
      Muscidae) in Kamphaengsaen Campus, Nakornpathom province, Thailand.
AB  - The seasonal changes and the daily activity of Stomoxyine species (Diptera:
      Muscidae) were examined, using Vavoua traps, in a dairy and a beef cattle farm in
      Nakhonpathom province, Thailand during July 2004 to June 2005. Over this period,
      Stomoxys calcitrans was the most commonly trapped species, followed by S. sitiens
      and S. indica. For the later species, this is the first report of its presence in
      Thailand. A total of 80 % of flies were captured during the rainy season from May
      to October and 20 % during the dry season from November to April. No major
      difference of fly density was observed between the dairy and the beef cattle
      farm. The activity pattern of S. calcitrans was diurnal with a peak between 08:00
      am to 10:00 am and another less marked one in the afternoon. The activity pattern
      of S. sitiens and S. indica was mainly crepuscular with 2 peaks, early in the
      morning (06:00 a.m.) and late in the afternoon (6:00 p.m.). Those species are
      important pests of livestock in Thailand, where they are known as a mechanical
      vector of trypanosomes. A better knowledge of their ecology is a prerequisite for
      more efficient control measures.

PMID- 17007218
TI  - Co-infection by Semliki forest virus and malarial parasite modulates viral
      multipucation, pathogenesis and cytokines in mice.
AB  - Environmental, technological and societal factors continue to have a dramatic
      effect on infectious diseases worldwide and are considered to be facilitating the
      emergence of several infectious diseases at a time. Co-infection with different
      species of viral and malaria infections are currently emerging problems of dual
      infection in the developing as well as developed countries. Understanding of
      interactions between the host, malaria and virus infection is of current concern
      and we have initiated studies to delineate the mechanisms involved during the
      progression of Semliki forest virus (SFV) and Plasmodium yoelii (P. yoelii)
      infection in mice. Enhanced virus multiplication and up-regulation of cytokine
      mRNA level in P. yoelii and SFV co-infected mice were observed on day 4 post
      infection compared to respective controls. Collectively, our observations
      indicate that malaria infection may influence virus multiplication, pathogenesis
      and up-regulation of cytokine mRNA during co-infection in mice.

PMID- 17007219
TI  - ELISA study of oocyst-sporozoite transition in malaria vectors.
AB  - Intrinsic vector characteristics and environmental factors affect the sporogonic
      development of P. falciparum in Anopheles mosquitoes. We tested for the presence
      of the circumsporozoite protein, as a marker of the oocyst to sporozoite
      transition in naturally infected Anopheles gambiae s.l. and Anopheles funestus.
      Malaria vectors were collected in a village in the Sahel of Niger during the
      rainy and dry seasons. ELISA-CSP was carried out on abdomen and head/thorax
      portions from more than 2000 samples. No significant difference was found in the
      overall rates of infection of An. gambiae s.l. (4.13%) and An. funestus (3.58%).
      Given the differences in duration of the two parasite stages, P. falciparum CSP
      antigen prevalence was nearly as high in the abdomen as in the head/thorax, and
      did not differ significantly between An. gambiae s.l. and An. funestus. These
      preliminary results suggest that development from oocysts to salivary gland
      sporozoites is similar in the two vectors. However, these developmental indices
      varied as a function of the season in which samples were collected, particularly
      for An. gambiae s.l. This simple method may be useful for field studies assessing
      the effect of environmental and genetic factors on parasite survival.

PMID- 17007220
TI  - Serodiagnosis of trichinellosis: in-house versus commercial ELISA.

PMID- 17007221
TI  - Cannabis and psychosis put in perspective.

PMID- 17007222
TI  - Is cannabis use a contributory cause of psychosis?
AB  - OBJECTIVE: To assess whether cannabis use in adolescence and young adulthood is a
      contributory cause of schizophreniform psychosis in that it may precipitate
      psychosis in vulnerable individuals. METHOD: We reviewed longitudinal studies of
      adolescents and young adults that examined the relations between self-reported
      cannabis use and the risk of diagnosis with a psychosis or of reporting psychotic
      symptoms. We also reviewed studies that controlled for potential confounders,
      such as other forms of drug use and personal characteristics that predict an
      increased risk of psychosis. We assessed evidence for the biological plausibility
      of a contributory causal relation. RESULTS: Evidence from 6 longitudinal studies
      in 5 countries shows that regular cannabis use predicts an increased risk of a
      schizophrenia diagnosis or of reporting symptoms of psychosis. These relations
      persisted after controlling for confounding variables, such as personal
      characteristics and other drug use. The relation did not seem to be a result of
      cannabis use to self-medicate symptoms of psychosis. A contributory causal
      relation is biologically plausible because psychotic disorders involve
      disturbances in the dopamine neurotransmitter systems with which the cannabinoid
      system interacts, as demonstrated by animal studies and one human provocation
      study. CONCLUSION: It is most plausible that cannabis use precipitates
      schizophrenia in individuals who are vulnerable because of a personal or family
      history of schizophrenia.

PMID- 17007223
TI  - What are the policy implications of the evidence on cannabis and psychosis?
AB  - OBJECTIVE: To explore the implications for mental health services, for health
      education about the risks of cannabis use, and for public policy toward cannabis
      use of observational evidence that cannabis use is a contributory cause of
      psychosis. METHOD: Using comparative analyses of similar evidence for the harmful
      effects of alcohol, tobacco, and amphetamine use, we considered the relation
      between observational evidence and action on cannabis. We examined arguments on
      the grounds of public health prudence for discouraging cannabis use by young
      individuals. With the assumption that the relation may be causal, we considered
      recommendations for policy in mental health services, health education, and
      public policy toward cannabis. RESULTS: The observational evidence and biological
      plausibility of the hypothesis that cannabis is a contributory cause of psychosis
      is at least as strong as evidence for causal relations between heavy alcohol and
      amphetamine use and psychosis. On public health grounds, there is a good case for
      discouraging cannabis use among adolescents and young adults. It remains
      uncertain how best to discourage use and at whom campaigns to reduce cannabis use
      should be targeted. CONCLUSIONS: We should discourage young adults seeking
      treatment in mental health services from using cannabis and inform them of the
      probable mental health risks of cannabis use, especially of early and frequent
      use. We must exercise caution in liberalizing cannabis laws in ways that may
      increase young individuals' access to cannabis, decrease their age of first use,
      or increase their frequency of cannabis use. We should consider the feasibility
      of reducing the availability of high-potency cannabis products.

PMID- 17007224
TI  - Going beyond: an adventure- and recreation-based group intervention promotes well
      being and weight loss in schizophrenia.
AB  - OBJECTIVE: To undertake a preliminary study to assess the feasibility of clinical
      implementation and evaluate the effectiveness of a novel adventure- and
      recreation-based group intervention in the rehabilitation of individuals with
      schizophrenia. METHODS: In a 2-year, prospective, case-control study, 23
      consecutively referred, clinically stabilized schizophrenia patients received the
      new intervention over an 8-month period; 31 patients on the wait list, considered
      the control group, received standard clinical care that included some
      recreational activities. Symptom severity, self-esteem, self-appraised cognitive
      abilities, and functioning were documented for both groups with standardized
      rating scales administered at baseline, on completion of treatment, and at 12
      months posttreatment. RESULTS: Treatment adherence was 97%, and there were no
      dropouts. Patients in the study group showed marginal improvement in perceived
      cognitive abilities and on domain-specific functioning measures but experienced a
      significant improvement in their self-esteem and global functioning (P < 0.05),
      as well as a weight loss of over 12 lb. Improvement was sustained over 1 year
      with further occupational and social gains. CONCLUSION: In the context of
      overcoming barriers to providing early intervention for youth and preventing
      metabolic problems among older adults with schizophrenia, adventure- and
      recreation-based interventions could play a useful complementary role.

PMID- 17007225
TI  - Suicide cases in New Brunswick from April 2002 to May 2003: the importance of
      better recognizing substance and mood disorder comorbidity.
AB  - OBJECTIVE: To investigate all suicide cases that occurred in New Brunswick in the
      14 months spanning April 1, 2002, to May 31, 2003, to determine 6-month and
      lifetime prevalence rates of psychopathology in the deceased. METHOD: We used 2
      psychological autopsy methods: direct proxy-based interviews and medical chart
      reviews, together with telephone contacts with informants. Consensus DSM-IV
      diagnoses were formulated by clinical panels on the basis of the Structured
      Clinical Interviews I and II for DSM-IV complemented by medical charts. RESULTS:
      Of the 109 suicide deaths identified by the coroner at the time of the study, we
      were able to investigate 102. At time of death, 65% of the suicide victims had a
      mood disorder, 59% had a substance-related disorder, and 42% had concurrent mood
      and substance-related disorders. The lifetime prevalence of substance-related
      disorders among these suicide victims was 66%. Finally, 52% of the suicide
      victims presented with a personality disorder; one-half of these were of the
      cluster B type. CONCLUSIONS: Although treatment of depression has frequently been
      recognized as the focal point of clinically based suicide-prevention efforts, our
      results underscore substance-related disorders as a key dimension of completed
      suicide. Suicide-prevention programs should be designed to address this problem
      more directly.

PMID- 17007226
TI  - Screening for major depression and posttraumatic stress disorder among asylum
      seekers: adapting a standardized instrument to the social and cultural context.
AB  - OBJECTIVE: To adapt the PTSD and MDE sections of a validated psychiatric
      diagnostic instrument, we used the Mini International Neuropsychiatric Interview
      (MINI) during an initial health assessment into a primary care facility for
      asylum seekers. METHOD: A 3-step process was carried out. First, items of the
      original version of the MINI were adapted to the specific context of life of
      asylum seekers in the host country (by a multidisciplinary group that included
      public health nurses, a primary care physician, a psychologist, a psychiatrist,
      and an epidemiologist). Second, we submitted the reworded and original versions
      of the MINI to 14 interpreters' who tested for general and cultural
      acceptability. Each diagnostic criterion was rated according to interpreters'
      comments on a 4-point Likert scale (1 = an item good for translation and 4 = an
      unusable or completely inadequate item). In the third step, we rephrased the most
      problematic items identified by the interpreters. RESULTS: Some original items
      were considered particularly ill-adapted for this context, and 4 had to be
      dropped. This final rewording took into account cultural inadequacies and lack of
      structure (including temporal organization) of the everyday life of newly arrived
      asylum seekers. CONCLUSION: The reworded MINI was successfully tested, and its
      items are presented in the final part of the study.

PMID- 17007227
TI  - Inattention, hyperactivity, and impulsivity in teenagers with intellectual
      disabilities, with and without autism.
AB  - OBJECTIVE: To explore inattentive, hyperactive, and impulsive behaviours in
      teenagers with intellectual disabilities (ID), with and without autism. METHOD:
      We identified teenagers with ID, with and without autism, in a single geographic
      area. Those with autism were matched for age, sex, and nonverbal IQ to those with
      ID only. We compared inattentive, hyperactive, and impulsive (IHI) behaviours in
      the 2 groups, along with adaptive functioning and medical circumstances. We
      further subdivided the autism group into those with IHI behaviours (autism IHI)
      and those without (autism non-IHI) and explored similarities and differences
      between autism subgroups. RESULTS: As a group, those with autism and ID had more
      IHI behaviours than those with ID alone. More in the autism group met criteria
      for attention-deficit hyperactivity disorder and hyperkinetic syndrome. Lifetime
      exposure to psychotropic medication was greater in the autism group, with
      stimulant and antipsychotic medications predominating. However, just under one
      half of those in the autism group showed no IHI behaviours. Comparison of autism
      IHI and autism non-IHI groups showed that those with IHI behaviours were
      significantly more likely to have past (but not current) exposure to stimulant
      medication. CONCLUSIONS: One in 2 teenagers with ID and coexisting autism
      displayed clinically significant inattentive, hyperactive, and (or) impulsive
      behaviours, compared with 1 in 7 of those with ID alone. Most of the remaining
      teenagers with autism displayed no IHI behaviours. Our results support the need
      for further investigation into the prevalence and etiology of these IHI
      behaviours in individuals with autism.

PMID- 17007228
TI  - Daycare attendance, stress, and mental health.
AB  - OBJECTIVE: Daycare stress can be indexed by cortisol, and elevated levels of
      cortisol have been implicated in the onset and development of mental health
      disorders. Our objective was to quantify the associations between daycare and
      cortisol and to identify individual and environmental conditions under which
      daycare attendance is associated with cortisol concentrations. METHODS: We used
      Cohen effect size statistics to quantify these associations and to compare them
      across 11 published studies that were identified with MEDLINE and PsycINFO.
      RESULTS: Cortisol levels increased during the daycare day, whereas they decreased
      when children stayed at home. The mean effect size was d = 0.72. The magnitude of
      the daycare-stress relation seemed to vary under 3 specific conditions. First,
      the effect size was larger for children in low-quality daycare (d = 1.15),
      whereas there was essentially little or no effect for children in high-quality
      daycare (d = 0.10). Second, the effect size was larger for preschoolers (aged 39
      to 59 months) (d = 1.17) than for infants (aged 3 to 16 months) (d = 0.11) or
      school-aged children (aged 84 to 106 months) (d = 0.09). Third, children with
      difficult temperaments in daycare were more likely to exhibit a rising pattern of
      cortisol, compared with children who were not difficult. CONCLUSIONS: Our review
      suggests that daycare attendance in relatively low-quality daycare conditions and
      for children with difficult temperaments may result in atypical cortisol
      elevation. Although the link between atypical cortisol elevation and mental
      health requires further study, programs aimed at improving the quality of daycare
      services during the preschool years are expected to lead to better physiological
      adaptation to daycare and to reduce the risks of mental health problems.

PMID- 17007229
TI  - Electroconvulsive therapy in older adults: 13-year trends.
AB  - OBJECTIVES: To examine temporal trends in electroconvulsive therapy (ECT) use
      among all 12 million Ontario residents between January 1992 and December 2004 and
      to examine the differential trends in older adults, compared with younger ones.
      METHODS: We undertook a time-series analysis to examine annual trends in the use
      and prevalence of ECT, using linked provincial datasets. Descriptive data were
      presented for the population as a whole, and then trends were described
      separately by age groups (younger and older). As a comparator, we similarly
      examined antidepressant prevalence for older adults over the same time period.
      RESULTS: Overall rates of ECT prevalence were stable. Annual population rates of
      individuals receiving ECT increased by about 27%, from 12.3 per 100 000
      population in 1992 to 15.6 per 100 000 in 1997, and then decreased to 12.5 per
      100 000 by 2004. The population rates of ECT were about threefold higher among
      older adults, relative to the younger population. Antidepressant prevalence
      increased by 90.1% among older adults over the same time period. The female-to
      male ratio was relatively stable over time. CONCLUSIONS: The rate of ECT has been
      relatively stable since the early 1990s. Older adults were much more likely to be
      prescribed a course of ECT than younger adults. ECT remains a commonly prescribed
      treatment, particularly in old age.

PMID- 17007230
TI  - Implicit memory for novel conceptual associations in amnesia.
AB  - In two experiments, we evaluated the status of implicit memory for novel
      associations in amnesia. Experiment 1 assessed priming in a category exemplar
      generation task in which contextual information associated with a target could
      increase the likelihood of target generation. Control participants, but not
      amnesic patients, showed associative priming. Amnesics' impairment was not due to
      the use of explicit memory by control subjects but reflected a genuine impairment
      in implicit memory for novel conceptual associations. Experiment 2 assessed
      priming in a relatednessjudgment task, in which associative priming was manifest
      as longer latencies for old than for recombined pairs of unrelated words. Amnesic
      patients showed intact associative priming in this task. We discuss differences
      in the status of implicit memory for novel conceptual associations in amnesia,
      with reference to the nature of the representation that supports priming in the
      two tasks and the type of processing that is required at test.

PMID- 17007231
TI  - Cultural differences in neural function associated with object processing.
AB  - Behavioral research suggests that Westerners focus more on objects, whereas East
      Asians attend more to relationships and contexts. We evaluated the neural basis
      for these cultural differences in an event-related fMRI study. East Asian and
      American participants incidentally encoded pictures of (1) a target object alone,
      (2) a background scene with no discernable target object, and (3) a distinct
      target object against a meaningful background. Americans, relative to East
      Asians, activated more regions implicated in object processing, including
      bilateral middle temporal gyrus, left superior parietal/angular gyrus, and right
      superior temporal/supramarginal gyrus. In contrast to the cultural differences in
      object-processing areas, few differences emerged in background-processing
      regions. These results suggest that cultural experiences subtly direct
      neuralactivity, particularly for focal objects, at an early stage of scene
      encoding.

PMID- 17007233
TI  - On the relations between implicit and explicit spatial binding: evidence from
      Balint's syndrome.
AB  - We report two experiments examining whether factors that affect binding in
      explicit report tasks also affect implicit binding in a patient with Balint's
      syndrome, G.K. Replicating prior studies, we showed that there could be implicit
      binding of visual features in a patient with Balint's syndrome who was at chance
      at explicitly discriminating the relations between the features. Nevertheless,
      when color-form relationships were coded, we showed that G.K.'s implicit binding,
      as well as his explicit report of binding relationships, was affected by the
      spatial distance between the stimuli. Similarly, we demonstrated effects of
      grouping on both implicit and explicit binding of the spatial relations between
      shapes. We interpret the qualitative similarities between implicit and explicit
      binding as indicating that they reflect a single process in which binding
      relations, initially established preattentively, are later consolidated by
      attention. This later process, of attentional consolidation, is disrupted in
      Balint's syndrome.

PMID- 17007232
TI  - Processing emotional pictures and words: effects of valence and arousal.
AB  - There is considerable debate regarding the extent to which limbic regions respond
      differentially to items with different valences (positive or negative) or to
      different stimulus types (pictures or words). In the present event-related fMRI
      study, 21 participants viewed words and pictures that were neutral, negative, or
      positive. Negative and positive items were equated on arousal. The participants
      rated each item for whether it depicted or described something animate or
      inanimate or something common or uncommon. For both pictures and words, the
      amygdala, dorsomedial prefrontal cortex (PFC), and ventromedial PFC responded
      equally to all high-arousal items, regardless of valence. Laterality effects in
      the amygdala were based on the stimulus type (word = left, picture = bilateral).
      Valence effects were most apparent when the individuals processed pictures, and
      the results revealed a lateral/medial distinction within the PFC: The lateral PFC
      responded differentially to negative items, whereas the medial PFC was more
      engaged during the processing of positive pictures.

PMID- 17007234
TI  - Behavioral, but not reward, risk modulates activation of prefrontal, parietal,
      and insular cortices.
AB  - Risky decisions may involve uncertainty about possible outcomes (i.e., reward
      risk) or uncertainty about which action should be taken (i.e., behavioral risk).
      Determining whether different forms of risk have distinct neural correlates is a
      central goal of neuroeconomic research. In two functional magnetic resonance
      imaging experiments, subjects viewed shapes that had well-learned response-reward
      contingencies. Magnitude of a monetary reward was held constant within one
      experiment, whereas expected value was held constant within the other. Response
      selection, in the absence of behavioral risk, evoked activation within a broad
      set of brain regions, as had been found in prior studies. However, behavioral
      risk additionally modulated activation in prefrontal, parietal, and insular
      regions,within which no effect of reward risk was observed. Reward delivery, in
      comparison with omission, evoked increased activity in the ventromedial
      prefrontal cortex and the nucleus accumbens. We conclude that distinct brain
      systems are recruited for the resolution of different forms of risk.

PMID- 17007235
TI  - Interference produced by emotional conflict associated with anterior cingulate
      activation.
AB  - The anterior cingulate cortex (ACC) is involved in cognition and emotion. In the
      classic Stroop task, presentation of stimuli that are in response conflict with
      one another produces activation in the caudal ACC. In the emotional Stroop task,
      presentation of emotionally salient stimuli produces activation in the rostral
      ACC. Presentation of stimuli that are emotionally conflicting should activate the
      caudal ACC; stimuli that are emotionally salient should activate the rostral ACC.
      We tested this prediction using functional magnetic resonance imaging while
      subjects made emotional valence judgments of words overlaid on emotional faces
      (word-face Stroop task). Emotionally incongruent pairs were responded to more
      slowly than emotionally congruent pairs. Emotionally incongruent trials were
      associated with increased activation within the caudal ACC, whereas no ACC
      activation was found in response to emotional saliency. These results support the
      conflict-monitoring model of caudal ACC and extend this function to conflict
      within the domain of emotional stimuli.

PMID- 17007237
TI  - Elevated levels of brain natriuretic peptide as a predictor of impaired coronary
      endothelial function in patients with left ventricular remodeling.
AB  - BACKGROUND: Plasma levels of brain natriuretic peptide (BNP) correlate with left
      ventricular remodeling, but the relationship between BNP induction and coronary
      function remains unclear. OBJECTIVES: The present study assessed BNP production
      in response to left ventricular enlargement and investigated the relationship
      between BNP production and coronary vasodilating function in patients with left
      ventricular remodeling. METHODS: Patients (n = 63) with normal or mildly diseased
      coronary arteries underwent Doppler flow study of the left anterior descending
      coronary artery. Vascular reactivity was examined using intracoronary
      acetylcholine, papaverine and nitroglycerin using a Doppler guidewire. RESULTS:
      Left ventricular end-diastolic dimension was positively correlated with BNP (r =
      0.45, p < 0.001) in all patients. BNP was significantly and inversely correlated
      with percentage change in coronary artery diameter induced by acetylcholine (r = 
      0.56, p < 0.001) but not by nitroglycerin (r = -0.20, p = 0.28) in patients with
      left ventricular end-diastolic dimension > or = 55 mm (n = 32). By contrast, BNP
      was not significantly correlated with percentage change in coronary artery
      diameter induced by either acetylcholine or nitroglycerin in patients with left
      ventricular end-diastolic dimension < 55 mm (n = 31). Further, BNP was not
      correlated with the percentage change in coronary blood flow induced by
      acetylcholine or by papaverine in patients with or without left ventricular
      remodeling. CONCLUSIONS: The elevation in plasma BNP levels that occurs in
      association with left ventricular enlargement is a predictor of impaired
      endothelium-dependent vasodilation in conductance coronary arteries.

PMID- 17007236
TI  - The role of awareness in delay and trace fear conditioning in humans.
AB  - Expression of conditional fear without awareness has been previously demonstrated
      during delay conditioning, a procedure in which the conditioned stimulus (CS) and
      unconditioned stimulus (UCS) overlap. However, less is known about the role of
      awareness in trace fear conditioning, where an interval of time separates the CS
      and UCS. The present study assessed skin conductance response (SCR) and UCS
      expectancy during delay and trace conditioning. UCS predictability was varied on
      a trial-by-trial basis by presenting perithreshold auditory CSs. Differential UCS
      expectancies were demonstrated only on perceived delay and trace trials. Learning
      related SCRs were observed during both perceived and unperceived delay CSs. In
      contrast, differential SCRs were demonstrated only for perceived trace CSs. These
      data suggest that awareness is necessary for conditional responding during trace,
      but not delay, fear conditioning.

PMID- 17007238
TI  - [Clinical manifestations and acute myocardial infarction in women treated with
      primary coronary angioplasty].
AB  - OBJECTIVES: The differences in presentation, complications, and outcome of acute
      myocardial infarction treated with primary coronary angioplasty were compared in
      male and female patients. METHODS: Consecutive patients with acute myocardial
      infarction who were admitted within 12 hr of onset underwent primary percutaneous
      coronary intervention, including 120 female (31%) and 264 male (69%) patients.
      RESULTS: There were significantly more patients with diabetes mellitus (42% vs
      31%, p = 0.03), and hyperlipidemia(56% vs 38%, p = 0.001), and fewer patients
      with current smoking (10% vs 60%, p < 0.0001) in the female group than in the
      male group (p < 0.01). The female group was significantly older (75 +/- 11 vs 67
      +/- 12 years, p < 0.0001). The value of acute phase brain natriuretic peptide was
      significantly higher (483 +/- 543 vs 306 +/- 404 pg/ml, p = 0.001), and peak
      creatine kinase value was significantly lower (1,743 +/- 1,732 vs 2,855 +/- 2,997
      IU/l, p = 0.0003) in the female group than in the male group. Both Killip's
      classification on admission (p = 0.04) and Thrombolysis in Myocardial Infarction
      grade soon after mechanical reperfusion therapy (p = 0.03) were significantly
      worse in the female group. There were significantly more patients with heart
      failure in the female group (40% vs 27%, p = 0.04). The cardiac mortality rates
      during 6 months was significantly higher in the female group (11% vs 5%, p =
      0.02). However, multivariate analysis showed that female sex was not an
      independent predictor of cardiac death. CONCLUSIONS: Female patients with acute
      myocardial infarction seemed to have a poor prognosis, in spite of lower peak
      creatine kinase value and higher brain natriuretic peptide value. The reasons for
      poorer outcomes in women were considered to be patient background, such as higher
      age and diabetes mellitus, and condition of heart failure on admission.

PMID- 17007239
TI  - [Relationship between high sensitive C-reactive protein and coronary plaque
      component in patients with acute coronary syndrome: Virtual Histology study].
AB  - OBJECTIVES: Elevated circulating C-reactive protein (CRP)is commonly observed in
      patients with acute coronary syndrome(ACS), suggesting enhanced inflammation in
      vulnerable plaques. However, few data are available on the relationship between
      the levels of CRP and the histological composition of coronary plaque. We
      investigated the relationship between plasma high sensitive CRP level and
      coronary plaque component with Virtual Histology intravascular ultrasound (VH
      IVUS). METHODS: Twenty eight patients with ACS and 37 patients with non-ACS were
      enrolled in the study. Plasma high sensitve CRP levels were measured before
      catheterization. A total of 125 lesions (ACS; 24 culprit lesions, 30 non-culprit
      lesions, non-ACS; 34 culprit lesions, 37 non-culprit lesions)underwent IVUS
      volumetric investigation, and the volume of plaque and media were calculated.
      Spectral analysis of IVUS radiofrequency data was performed with VH software, and
      plaque and media were classified into fibrous, fibro-fatty, dense calcium, and
      necrotic core elements. RESULTS: Although the plasma high sensitive CRP level in
      patients with ACS was higher than that in those with non-ACS (0.26 +/- 0.2 vs
      0.15 +/- 0.17 mg/dl, p < 0.05), necrotic core volume was not different between
      the two groups(11.7 +/- 7.3 vs 12.3 +/- 7.2mm3/cm, p = 0.71). There was a
      positive correlation between high sensitve CRP and necrotic core volume in
      patients with ACS, not only in culprit lesions (p = 0.0004, r2 = 0.564) but also
      in non-culprit lesions (p = 0.0008, r2 = 0.473), whereas patients with non-ACS
      showed no correlations. CONCLUSIONS: IVUS spectral analysis revealed that
      elevated plasma high sensitve CRP level was correlated with necrotic core volume
      in patients with ACS, both in culprit and non-culprit lesions, suggesting
      enhanced vascular inflammation.

PMID- 17007241
TI  - Successfully treated massive pulmonary thromboembolism and thrombus in the right
      atrium due to diffuse malignant lymphoma: a case report.
AB  - A 40-year-old man presented with massive pulmonary embolism related to diffuse
      large B cell lymphoma. His hemodynamic state worsened rapidly to shock after
      sudden onset of dyspnea. Echocardiography and thoracic computed tomography
      indicated pulmonary thromboembolism due to deep venous thromboembolism,
      associated with a mass in the anterior mediastinum and a 5 x 8 cm mass in the
      left pelvis compressing the left femoral vein. He underwent emergent surgery to
      remove a huge thrombus from the right atrium through the bilateral pulmonary
      arteries. Soon after this surgery, his hemodynamic state recovered and excision
      of the left cervical lymph node revealed diffuse large B cell lymphoma. Venous
      compression by the lymphoma mass had caused hemostasis and thrombus formation in
      the present case.

PMID- 17007240
TI  - Transient left ventricular apical ballooning developing after the Central Niigata
      Prefecture Earthquake: two case reports.
AB  - Two patients presented with transient left ventricular apical ballooning
      (takotsubo cardiomyopathy) induced by emotional stress caused by the Central
      Niigata Prefecture Earthquake in 2004. These patients complained of chest pain
      immediately after the earthquake. In patient 1, electrocardiography (ECG) showed
      slight ST elevation in leads V5 to V6 and 1 mm ST depression in lead III. Serial
      ECG revealed inverted giant T waves in leads V3 to V6 and inverted T waves in
      leads I, II, aVL and aVF 13 days after the earthquake occurred. Patient 2 also
      complained of chest pain right after the earthquake, but consulted a doctor 15
      days after the earthquake occurred. ECG showed inverted giant T wave in leads V1
      to V6 and inverted T waves in leads I, II and aVL. Transthoracic echocardiography
      showed hypokinesis of the apical area of the left ventricle with normokinesis in
      the basal area in both patients. Coronary angiography showed no stenotic segments
      and coronary spasms were not induced by provocative testing. Serial cardiac
      radionuclide single photon emission computed tomography of myocardial functional
      sympathetic innervation using iodine-123-metaiodobenzyl-guanidine (MIBG) and
      thiallium-201 (201Tl) showed an MIBG uptake defect and increased wash-out in the
      apical area, but only mild decrease of apical 201Tl uptake. Due to strong
      emotional stress, earthquakes may induce transient left ventricular apical
      ballooning (takotsubo cardiomyopathy).

PMID- 17007242
TI  - [Percutaneous transluminal angioplasty via dorsalis pedis artery for chronic
      total occlusion of superficial femoral artery: a case report].
AB  - A 60-year-old woman with intermittent claudication underwent angiography, which
      showed total occlusion of the left superficial femoral artery and no distal flow.
      Computed tomography with contrast medium revealed that the occlusion extended to
      the popliteal artery but distal flow was maintained to the dorsalis pedis artery.
      Percutaneous transluminal angioplasty was attempted via the right femoral artery,
      but the guidewire could not be advanced. Therefore, a 4F sheath was inserted into
      the dorsalis pedis artery and the guidewire was passed through the occluded
      lesion. After pre-dilation, the guidewire was re-crossed from the right femoral
      artery and two stents were successfully implanted. Finally sufficient antegrade
      blood flow was achieved after the procedure. The trans-dorsalis pedis artery
      approach is a valuable option for the percutaneous transluminal angioplasty of
      long superficial femoral artery occlusion if the antegrade approach is
      impossible.

PMID- 17007243
TI  - [Severe aortic regurgitation with mild ascending aortic dilatation].

PMID- 17007244
TI  - [Guidelines for clinical use of cardiac nuclear medicine (JCS 2005)].

PMID- 17007245
TI  - [Review: diagnostic methods for the detection of porcine reproductive and
      respiratory syndrome virus (PRRSV) infections].
AB  - This review describes methods that have been developed for the diagnose porcine
      reproductive and respiratory syndrome virus (PRRSV) infections. It summarizes the
      organs and tissues which should be sampled and the sampling times, and methods to
      detect viral RNA, viral antigens, and antibodies directed against PRRSV. The
      sensitivity, specificity, and limitations of the various tests are also
      described.

PMID- 17007246
TI  - [UGCN warns for Klebsiella mastitis].

PMID- 17007247
TI  - [Human, animal and veterinarian].

PMID- 17007248
TI  - [From use to enjoyment of the human-animal relationship].

PMID- 17007249
TI  - [A good mouth].

PMID- 17007250
TI  - [The recognizable specialist?].

PMID- 17007251
TI  - [The weight of a signature of a Dutch Veterinarian].

PMID- 17007252
TI  - [He always gave a discount...].

PMID- 17007253
TI  - [Are the square milking devices the future?].

PMID- 17007254
TI  - [(With) the PAO-D continuing the academic year 2006-2007].

PMID- 17007255
TI  - [Pathophysiology and management of perioperative hypothermia].
AB  - The paper is a review of pathophysiology and management of perioperative
      hypothermia. The advanced methods of rewarming, such as passive and active:
      external and core used in clinic allow for efficient management ant prophylactics
      of hypothermia. Thermotherapy with use of infrared ceiling heaters CTS and mobile
      MTC as well as Infutherm system applying by authors are desirable and even
      indispensable in contemporary equipment of surgery clinics, cardiovascular
      surgery clinics and burn centers. The ideal rewarming method should be safe and
      enable fast, reliable and predictable warming or rewarming. The clinical
      parameter to determine the efficacy of rewarming is the change of core
      temperature. There is no doubt that active warming with forced-air warmers (Warm
      Touch 5700 and Bair Hugger 500) or radiative heaters (IR-A:Hydrosun 500, IR-C
      radiation: CTC X, MTC) is more effective than use of standard, passive insulation
      hospital blankets or convectional heaters. Actually the forced-air warmers are
      counted to be more useful in cardiovascular surgery hypothermia management,
      because of fast rate core temperature rise and faster rise in mean skin
      temperature compared to the control group. CTC X and MTC Aragona radiative
      heaters are useful in burn management being the most effective when the distance
      of heater from the patient body is less than 80 cm. The observation of 60
      consecutive extensive burns leads to conclusion that long-lasting dressings in
      burn patients when the whole body is not covered and protected, can be performed
      safely only in conditions excluding heat losses and core temperature drop. While
      the cold intravenous fluids may significantly contribute to the temperature drop
      depending on the volume infused, the use of fluids warming systems as well as
      external heat application is absolutely indicated to improve the heat balance of
      the patient body.

PMID- 17007256
TI  - [Prevalence of dangerous arrhythmia during pharmacological stress
      echocardiography].
AB  - Pharmacological stress echocardiography (SE) has become a routine diagnostic and
      prognostic method in patients with ischemic heart disease. However, all stress
      tests can provoke undesirable adverse effects including dangerous arrhythmia. The
      aim of the study was to access the prevalence and types of arrhythmia that can
      appear during SE. MATERIALS AND METHODS: A retrospective study included the
      cohort of patients studied using SE in our Department of Cardiology between 1995
      and 2002. We followed the data of 836 patients (pts) (615 men, aged 52 +/- 5
      yrs). Dobutamine SE was performed in 695 pts (83.2%) and dipyridamole SE in a
      group of 141 pts (16.8%). Additionally, atropine was administrated to achieve
      submaximal heart rate in a group of 694 pts (83%). 519 pts (62%) underwent SE was
      performed according to high dose protocol and in 317 pts (35%)--low dose
      protocol. RESULTS: During SE the following arrhythmia events were observed: one
      persistent ventricular tachycardia (0.12%) and two paroxysmal atrial fibrillation
      (0.24%) in dobutamine test. The set of unsustained ventricular tachycardia in six
      patients (0.72%) 5 patients from dobutamine group and 1 from dipyridamole group).
      Complex forms of ventricular extrasystoles (as bigeminy and trigeminy) in 46 pts
      (5.5%) 43 in dobutamine SE and 3 in dipyridamole SE. All arrhythmias were mild
      and withdrew spontaneously or after beta-blockers administration. CONCLUSIONS:
      The risk of dangerous arrhythmia during either dobutamine SE or dipyridamole SE
      is small and similar in both groups. Dobutamine SE tends to provoke of mild
      arrhythmia (p = 0.075) more often.

PMID- 17007257
TI  - [Evaluation of surgical treatment of mitral valve defect in patients with chronic
      renal failure].
AB  - Renal failure of patients qualified for open-heart surgical treatment seems to be
      very important problem since years. The operation with extracorporeal circulation
      is large burden for kidneys and there is huge risk of intensifying of existing
      failure. The aim of the study was the evaluation of renal parameters,
      complications occurrence and mortality of patients with chronic renal failure
      (ChRF) (grade II--mild ChRF) subjected to mitral valve replacement. MATERIALS AND
      METHODS: To retro- and prospective analysis were subjected 34 patients with
      severe mitral valve defect, subjected to operation between 1998 and 2002 in
      Department of Cardiac Surgery in Lodz. All patients included to study had
      increased level of creatinine--1, 5-3, 0 mg/dl (at least in three measurements).
      All examined patients were subjected to artificial mitral valve replacement and
      13 patients to simultaneous tricuspid valve plastic surgery. Postoperative
      evaluation of clinical condition and renal parameters was performed twice: early
      (till 30 day after operation) and long-term (after meanly 14 months). RESULTS: In
      seven patients, in early postoperative period, it was necessary to implement
      extracorporeal dialysis with artificial kidney dialysis machine. Among these
      patients we ascertained three deaths (intrahospital mortality was 8.8%). During
      long-term observation we noted two cases of infective endocarditis requiring
      reoperation and re-implantation of mitral valve. During this time of observation
      only one death was noted (post-hospital mortality was 3.2%). CONCLUSIONS:
      Dysfunction of kidneys, even in mild degree, causes significant increase of risk
      of early death (about 2.5 times). In most research population in long-term
      observation we ascertained the large improvement of kidney functions (significant
      decrease of creatinine level; p < 0.001). Concomitant tricuspid valve
      regurgitation, requiring plastic surgery is an additional factor incriminating
      long-term results of surgical treatment.

PMID- 17007258
TI  - [Aortic valve replacement in patients with heart failure].
AB  - Severe aortic regurgitation and stenosis are urgent indication for aortic valve
      replacement in patients with left ventricular dysfunction, however the effect of
      cardiac surgery may differ in both groups. The aim of the study was to evaluate
      the early changes of haemodynamic parameters of heart: ejection fraction,
      endsystolic and enddiastolic left ventricle diameters, endsystolic and
      enddiastolic left ventricular wall thickness and left atrium diameter, depending
      on ejection fraction value (EF), in patients undergoing aortic valve replacement
      due to isolated aortic stenosis or regurgitation. MATERIALS AND METHODS: 250
      patients engaged to the study were subjected to the mechanical aortic valve
      replacement in Cardiac Surgery Department in Lodz. All patients were divided into
      two groups--patients operated due to aortic regurgitation and aortic stenosis.
      Then each group, depending on EF volume before operation, was divided into two
      subgroups (A - EF between 35 and 50%; B - EF below 35%). RESULTS: Comparing the
      pre- and early postoperative period, ejection fraction rose markedly in both
      subgroups of patients with aortic stenosis and the highest increase was
      ascertained in subgroups A. Analyzing endsystolic and enddiastolic left ventricle
      diameters we observed the reduction of left ventricle diameters in all groups.
      Evaluating endsystolic left ventricular wall thickness we observed the increase
      of wall thickness in both subgroups B. Analogically enddiastolic left ventricular
      wall thickness increased in all analyzing groups, whereas in groups with lowest
      fraction the rise was essential. CONCLUSIONS: Aortic valve replacement both due
      to aortic stenosis and regurgitation is associated with improved haemodynamic
      status in early postoperative period.

PMID- 17007259
TI  - [Evaluation of some selected structural and functional parameters of red blood
      cells as oxidative stress markers in elderly people with primary hypertension].
AB  - The aim of the study was to evaluate the degree of membrane lipid peroxidation,
      internal microviscosity, activity of both total and Na+, K+ membrane ATP-ase and
      markers of oxidative damage of membrane protein in erythrocytes of elderly people
      with primary hypertension. MATERIAL AND METHODS: The examination was performed on
      50 people. The first group (HA) consisted of 15 elderly people with primary
      hypertension (mean age 71, 3 years old). The reference groups were formed with
      healthy elderly people (K1) (15 people, mean age 72, 4 years old) and younger
      healthy people (K2) (20 people, mean age 55, 3 years old). RESULTS: Membrane
      lipid peroxidation of red blood cells was significantly increased in the group of
      elderly people with primary hypertension (HA). The lowest level of lipid
      peroxidation was observed in the (K2) normotensive group of younger people.
      Erythrocyte internal microviscosity was significantly higher in the group of
      healthy elderly people (K1) compared with the group of healthy younger people
      (K2). In HA group additional essential increase in microviscosity was observed in
      comparison with K1 and K2. The activity of both total and Na+, K+ membrane ATP
      ase was significantly the highest in the group of younger people and the lowest
      in the group of elderly people with primary hypertension. In HA group increased
      damage of membrane protein was observed that was indicated by the reduced -SH
      group content and the increased value of W/S parameter in comparison with K1 and
      K2 groups. CONCLUSIONS: The obtained results indicate that in the elderly people
      with accompanying primary hypertension the whole-body oxidative stress is
      increased, which may be indicated by structural and functional oxidative damage
      of red blood cells. These observations may be significant in the pathogenesis of
      hypertension complications. This observation may be important in the pathogenesis
      of hypertension complications in this period of life.

PMID- 17007260
TI  - [Estimation of the effect of lipoic acid in the rat's lung during
      lipopolysaccharide-induced oxidative stress].
AB  - The aim of this study was to investigate the effect of lipoic acid (LA) on lipid
      peroxidation, hydrogen peroxide concentration (H2O2), sulphydryl group (-SH)
      contents and total capacity protein a few hours after administration
      lipopolysaccharide (LPS) -induced oxidative stress in rats. MATERIALS AND METODS:
      Male albino Wistar rats were used in this study. The animals were divided into
      four groups, each group consisting of ten male animals. Control group received
      physiological saline alone i.v. The second group was given LA (60 mg/kg b.w.,
      i.v.). The third second group received LPS (30 mg/kg b.w., i.v.). The fourth
      group received LPS (30 mg/kg b.w., i.v.) and after 0.5h received LA (60 mg/kg
      b.w., i.v.). In the lung homogenates were measured thiobarbituric acid reactants
      (TBARS), hydrogen peroxide concentration, -SH groups and protein contents.
      RESULTS: The administration of LA after to LPS -induced oxidative stress caused a
      significant decrease in TBARS and H2O2 concentrations (appropriate 3.65 +/- 0.2
      microM and 0.014 +/- 0.008 microM) compared with the group treated with LPS
      (appropriate 6.030 +/- 0.16 microM and 0.189 +/- 0.03 microM). Treatment of LPS
      injected rats with LA caused increase in -SH groups and protein concentration (p
      < 0.05). CONCLUSION: The early administration of LA a significant decreased
      symptoms of oxidative stress - induced LPS, that shows decrease in lipid
      peroxidation process, H2O2 concentration and increase in -SH groups and protein
      contents in rat's lung homogenates.

PMID- 17007261
TI  - [Application of VEGF165 plasmid in treatment of critical lower limb ischemia].
AB  - In the study we assessed the clinical and histological benefits of gene therapy
      in no-option patients with critical lower limb ischemia. MATERIAL AND METHODS: We
      administrated VEGF165 (Vascular Endothelial Growth Factor) plasmid to 10
      patients. The plasmid was injected intramuscularly into lower limb. In the study
      we evaluated: clinical outcomes, venous blood VEGF protein concentration before
      and after (7th, 14th, 28th and 90th day) administration of plasmid. From patients
      who required amputation we obtained samples of muscles, which were examined
      histological and by PCR (Polymerase Chain Reaction) for detection of plasmid
      genes. RESULTS: Only two patients from the group did not require amputation due
      to the therapy. In eight patients the operation was essential. Serum VEGF
      concentration was higher than in healthy controls (p < 0.05). We observed
      increase of the concentration of the cytokine on the 14th day an decrease on the
      90th day after administration of plasmid (p < 0.05). Histological analysis did
      not reveal any sings of new blood vessels formation in the samples taken from
      amputated limbs. There was also no signs of expression of plasmid primers in PCR.
      CONCLUSIONS: The therapy is safe. We did not observe significant improvement in
      patient's clinical state. The therapy needs further investigations.

PMID- 17007262
TI  - [Post transfusion purpura--a serious underdiagnosed delayed post-transfusion
      event].
AB  - Post-transfusion purpura (PTP), a delayed post-transfusion event, is
      underdiagnosed, not only in Poland. Thrombocytopenia results from the destruction
      of patients' and transfused platelets by platelet specific antibodies (anti-HPA).
      The incidence of PTP is not estabilished. THE AIM: Analysis of 10 cases with PTP
      diagnosed in Poland during last 25 years. MATERIAL AND METHODS: 9 women and 1 man
      with normal platelet count who developed thrombocytopenia with diathesis
      haemorrhagica after transfusion of red cells or/and platelets. Platelet specific
      antibodies (anti-HPA) were examined by the platelet immunofluorescence test and
      by the monoclonal immobilization of platelet antibodies (MAIPA) assay; leucocyte
      antibodies by standard lymophocytotoxicity test (LCT). RESULTS: In all 10
      patients the PTP was diagnosed because: 1) thrombocytopenia with diathesis
      haemorrhagia occured 3-10 days after the transfusion (in 5 cases blood was
      transfused during the operation), 2) in all the patients anti-HPA were detected
      (in 9- anti-HPA-1a, in 1 case anti-HPA-3a), 3) a primary HPA alloimmunization was
      very probable. A recovery of platelets count occured in 6 patients within 8-34
      days after corticosteroids and/or IVIG, however, therapeutic effect of them was
      difficult to assess due to a great probability of spontaneous remission up to 1
      month. Four patients died due to their basic disease although the impact of the
      PTP cannot be excluded. CONCLUSION: The diagnosis of PTP was possible because of
      the detection of anti-HPA antibodies in patients who developed thrombocytopoenia
      after blood transfusion.

PMID- 17007263
TI  - [Assessment of malonyldialdehyde concentration as a product of lipid peroxidation
      and lipid metabolism in patients on chronic dialysis].
AB  - Chronic hemodialysis in patients with renal insufficiency is a factor
      significantly intensifying oxidative stress, resulting in increased lipid and
      lipoprotein peroxidation. It intensifies atherosclerotic activity.
      Malonyldialdehyde (MDA) concentration in serum, and isolated fraction of low
      density lipoprotein is indicators of lipid peroxidation intensification and
      therefore arteriosclerosis development. THE AIM OF THE STUDY: Assessment of MDA
      concentration as a product of lipid peroxidation and lipid metabolism in patients
      on chronic dialysis. MATERIALS AND METHODS: The study included 48 dialyzed
      patients, age 22-68 undergoing chronic dialysis for, on average, 56 months. On
      account of dialysis period the patients were included into 3 subgroups: group 1
      (n = 17) dialysis period 2 years, group 2 (n = 13) dialysis period 2-5 years and
      group 3 (n = 18) dialysis period longer than 5 years. Control group consisted of
      30 healthy subjects. We assessed: malonyldialdehyde in serum and isolated
      fraction of low density lipids (LDL) and high density lipid (HDL) and cholesterol
      (CH) and triglycerides (TG), phospholipids (PL) in serum and isolated lipoprotein
      fractions. RESULTS: Significantly decreased levels of HDL, LDL fractions and
      increased triglicerides and elevated levels of MDA in serum and isolated LDL
      fraction were found in patients on chronic dialysis in comparison to control
      group (p < 0.05). CONCLUSION: Our results indicate apparent normalization of
      lipid metabolism in patients on chronic dialysis and suggest that MDA assessment
      is better marker for arteriosclerosis risk estimation in long-term dialyzed
      patients.

PMID- 17007264
TI  - [Serum cystatin C concentration in children with urinary stones].
AB  - Stone formation precedes long period, when the crystals are accumulated in
      basement membranes of renal tubules and intestinal tissue. Accumulated, inside of
      renal tubules crystals and stones in urinary tract cause urinary tract
      obstruction, what may lead to impairment of renal function. The aim of work was
      the assessment of serum cystatin C (cys C) concentration in children with
      urolithiasis, confirmed by the presence of renal stones in renal pelvis in
      comparison to serum creatinine concentration and creatinine clearance (Cr cl).
      MATERIAL AND METHODS: Examined group (B) consisted of 30 children aged (13.08 +/-
      4.14 years) with urolithiasis, which was divided into 3 subgroups (I, II, Ill) in
      dependence on stones' diameter (0.35-1.6cm). Control group (C) consisted of 26
      healthy children at the same age. Nephelometric method was used to determine
      serum cystatin C level, Jaffe method to assess serum creatinine and the Schwartz
      formula to estimate glomerular filtration rate. RESULTS: In control group (C)
      serum cys C did not exceed 0.95 mg/l. In group B serum cystatin C and serum
      creatinine concentration and Cr cl was similar to the results of control group (p
      > 0.05). However in 16% of children with urolithiasis, in whom the stones of 0.8
      1.6cm diameter were found in both renal pelvis, the concentration of serum cys C
      exceed 1.2 mg/l, and the value differed significantly from the results of control
      group (p < 0.05). A weak positive correlation between cys C and creatinine
      concentration and also between cys C and Cr cl was found. The serum cys C
      concentration in children with single stones of 0.35-0.8 diameter was normal.
      CONCLUSION: Serum cystatin C increases with increased degrees of urolithiasis
      assessed by stone size and their number in kidney.

PMID- 17007266
TI  - [Adrenal tumours in a selected 10-years surgical material].
AB  - The aim of the study was to analyze the number and proportions of different
      adrenal tumours resected during the last 10 years in our centre. Besides, we seek
      correlations between the size of tumours and the age and body mass indexes (BMI)
      of the examined patients. MATERIAL AND METHODS: The tumours where measured on CT
      and MRI before surgery, and on pathological examination after resection. The
      examined group consisted of 69 patients, 22 males and 47 females, mean age 50.51
      +/- 12.26 yrs. In 45 (65.22%) cases the right adrenal was affected, in 21
      (30.43%)--the left, in 3 (4.35%)--both. RESULTS: 12 adrenocortical cancers, 20
      phaeochromocytomas, 9 cortisol-secreting adenomas, 4 aldosteronomas, 18
      hormonally inactive adenomas, 6 miscellaneous tumours were found. Malignant
      tumours where significantly larger than benign (12.20 +/- 6.81 vs 6.71 +/- 5.62
      cm, p < 0.005). We observed no correlation between the age and preoperative tumor
      size (p = 0.1756), between the age and pathological tumor size (p = 0.3601), and
      between BMI and the preoperative and histopathologic size (p = 0.4204, and p =
      0.6478, respectively). CONCLUSIONS: The most common tumour was phaeochromocytoma.
      Most tumours where found in the right adrenal. The malignant tumours where larger
      than benign ones. No correlations between age and BMI, and tumour size where
      demonstrated.

PMID- 17007265
TI  - [Evaluation of influence of selenium, copper, zinc and iron concentrations on
      thyroid gland size in school children with normal ioduria].
AB  - Proper diet with regard to quantity and quality of meals is of vital importance
      for normal development and functioning of the organism. There are many proofs
      that environmental factors play an important role in the pathogenesis of goiter.
      Iodine deficit in diet is best known of all factors contributing to goiter.
      Deficit of other elements like, iron, selenium, copper and zinc is also
      essential. The purpose of this study was to evaluate the influence of chosen
      environmental factors, i.e., iron and trace elements of selenium, zinc and copper
      -essential for the thyroid functioning on the development of goiter in school
      children aged 6-13 years with normal ioduria in the Polish population. MATERIAL
      AND METHODS: In 2002, the study was performed in 4 elementary schools chosen
      randomly in Bialystok and in the Children's Outpatient Clinic of Endocrinology of
      the Specialist Regional Hospital. The study included 400 children aged 7-13 years
      from schools and 120 patients at the same age treated with KJ and/or tyroxine for
      minimum 12 months due to goiter in the Out-patient Clinic of Endocrinology.
      Basing on the assessment of the thyroid size as well as the criteria of WHO from
      1997 year for body surface and sex, children were divided into 2 subgroups: with
      goiter and the thyroid gland within the norm. Children aged 9-11 years were
      qualified and chosen from subgroups to further examinations. In both subgroups,
      blood samples were taken to determine concentrations of iron, selenium, copper
      and zinc. RESULTS: The mean concentration of selenium in the blood was
      statistically significantly lower in children with goiter in comparison with
      children with the thyroid gland within the norm (44.4 +/- 7.8 microg/L vs. 49.2
      +/- 9.1 microg/L, p = 0.044) in the study population of school children and the
      Outpatient Clinic of Endocrinology. No differences of serum iron concentrations
      were observed in children with goiter and with the thyroid gland within the norm.
      However, nearly the half (45.5%) of patients with the lower serum concentration
      of iron (< 60 microg/dL) had goiter despite average 22-month therapy with KJ
      and/or tyroxine. CONCLUSION: Observed, in spite of proper iodine prophylaxis, 7%
      rate of goiter occurring in school children suggests other than iodine deficiency
      factors that influence goiter development. The study proved that the low
      concentration of iron and/or selenium deficit found in the serum of children with
      goiter in spite of their treatment with KJ and/or tyroxine may be additional
      factors influencing the effectiveness of this treatment.

PMID- 17007267
TI  - [SP-selectin and beta-TG as serum markers of platelet activation in menopausal
      women with depression].
AB  - During activation, blood platelets (PLT) release a number of micromolecular
      compounds, of which P-selectin and beta-thromboglobulin (beta-TG) are considered
      the major markers of the activation. The activated platelets and the released
      micromolecular compounds actively participate in thromboembolic disorders
      frequently observed in menopause. Low estrogen level in menopausal women is a
      common cause of depressive disorders. The aim of the study was to compare the
      state of PLT activation in menopausal women with and without depression. The
      assessment of PLT activation was based on the concentration of sP-selectin and
      beta-TG as serum markers of the activation. MATERIAL AND METHODS: Among 65
      menopausal women examined, 16 (approx. 25%) had depression. PLT activation was
      assessed on the basis of sP-selectin and beta-TG levels. The investigation was
      performed in the low-platelet citrate serum obtained from venous blood collected
      onto anticoagulant. The levels of beta-TG and sP-selectin were determined using
      the immunoenzymatic method, with ELISA Kit reagents. RESULTS: In all the women,
      both with and without depression, the levels of beta-TG and sP-selectin several
      times exceeded the accepted norms. The concentration of beta-TG was statistically
      significantly higher (p < 0.05) in women with depression as compared to those
      with no depressive disorders. CONCLUSIONS: Menopausal women suffering from
      depression show enhanced intravascular platelet activation. High beta-TG level in
      women with depression indicates higher risk of thromboembolic disorders in
      comparison with depression-free women in menopause.

PMID- 17007268
TI  - [The dynamics of changes glucose concentration of patients with ischemic stoke in
      chosen times of day].
AB  - Cerebral ischemic stroke which basic exponent is an sudden occurrence of
      neurological deficits is also characterized by deep disturbances of human
      organism homeostasis. It is known that many functions of a healthy human organism
      is subjected to the rhythmical changes during the twenty-four hours, and the
      state of illness can disturb them in a crucial way. The aim of the study was to
      examine the dynamics of changes of glucose concentration in blood of patients
      with acute phase of cerebral ischemic stroke in chosen times of day. MATERIAL AND
      METHODS: The examinations were carried out on 16 non-diabetic patients (11 men, 5
      women), aged between 57 and 76 where the cerebral ischemic stroke was confirmed
      by the Computer Tomography of the head. The patients were on high protein diet
      with total energy value of 2283 +/- 130.0 kcal per twenty-four hours in three
      meal times: at 09AM, 02PM, 06PM. The venous blood for examinations was drawn 6
      times during the day: at 01AM, 05AM, 09AM, 01PM, 05PM, 09PM on the 1st, 3rd, 5th
      and 10th day after the stroke occurred. The following concentrations in blood
      were denoted glucose. RESULTS: In patients with the acute phase of cerebral
      ischemic stroke the significant disorders of carbohydrate metabolism can be
      observed in times between 09AM and 01PM on both the 1st, 3rd and the 5th day of
      the duration of the disease. CONCLUSIONS: The received results may take effect in
      the proofreading of pharmacological treatment with the consideration of the times
      of day.

PMID- 17007269
TI  - [Evaluation of effectiveness of the micrographia's therapy in Parkinson's disease
      patients].
AB  - Micrographia is one of the characteristic symptoms of Parkinson's disease. Its
      cause is hypokinesia (reduced movement's amplitude). The methods of management of
      micrographia are founded on the assumption that the important cause of prolonged
      hypokinesia in Parkinson's disease patients is impairment of attention. The aim
      of the work was to analyse relationship between an occurrence and intensity of
      micrographia and others clinical features of Parkinson's disease. The another aim
      was to assessment of effectiveness of micrographia's management. MATERIAL AND
      METHODS: 40 Parkinson's disease patients (19 women and 21 men) aged from 49 to 82
      years (mean--65.5) were examined. In the analysis age, duration of disease,
      predominance of right- or left - side symptoms, impairments of concentration of
      attention, dosage of levodopa, UPDRS score, and the level on the Hoehn and Yahr's
      scale were taken into account. In therapy of micrographia three methods were
      managed: writing between lines determining desired height of letters, writing
      with a big dot as a guide for letter's size and regular reminding the patient of
      the need to write at bigger size. RESULTS: micrographia was occurred in 30 of 40
      Parkinson's disease patients (75%). The better writing magnitude was obtained in
      all patients, but in 16 patients the effect was much better and maintained to 6
      hours, whereas in 14 patients the effect was worse and maintained only short
      time. No relationship was found between an applied method of therapy and its
      effect. A significant statistical relationship was established between
      impairments of concentration of attention and a worse effect micrographia's
      therapy. CONCLUSIONS: Micrographia occurs in 75% Parkinson's disease patients.
      The therapy is successful in more than 50% of patients. Impairments of
      concentration of attention exert an adverse effect on micrographia's therapy.

PMID- 17007270
TI  - [The venous ulcer therapy in use of the selected physical methods (Part 2)--The
      comparison analysis].
AB  - The aim of the study was to evaluate the influence of a high voltage stimulation,
      sonotherapy and laser biostimulation on the process of healing of venous leg
      ulcers. MATERIAL AND METHODS: Four comparative groups--A, B, C and D--were made
      at a random from 92 patients with venous leg ulcers. The group A consisted of 26
      patients, the group B--21 patients, the group C--21 patients, and the group D--24
      patients. The patients in all comparative groups were treated pharmacologically.
      Ulcerations at the patients in the group A were additionally treated with the
      high voltage stimulation. However, ulcerations at the patients in the group B
      were treated with the sonotherapy. Ulcerations at the patients in the group C
      were treated with the laser biostimulation. Changes of the area, length, width
      and volume of the tissue defekt after above physical therapies were assessed.
      Changes of the pus decontamination and granulation processes were observed too.
      CONCLUSIONS: After treatment concluded, high voltage stimulation and ultrasound
      therapy had been more efficient at enhancing healing of venous leg ulcers than
      topical pharmacology. No significant effect of laser biostimulation on healing
      process was observed.

PMID- 17007271
TI  - [Acute myocardial ischemia after carbon monoxide exposure: a case report].
AB  - We describe the case of a patient who was admitted to the internal ward because
      of carbon monoxide poisoning. The examined level of carboxyhemoglobin measured
      32%. The patient did not complain of any chest pain, but the features of
      myocardial hypoxia were observed in the electrocardiogram and significantly
      increased level of troponin T was revealed in laboratory tests. The ischaemic
      abnormalities ceased after normalization of carboxyhemoglobin level and the
      stress test was negative. Within the submitted study we report the possible
      interaction between carbon monoxide and cardiovascular system.

PMID- 17007272
TI  - [Massive bleeding from the upper digestive tract in patients with pseudoaneurysm
      of splenic artery].
AB  - Pancreatic pseudocysts are common complication of both chronic and acute
      pancreatitis. Sanguination from damaged peripancreatic vessels into the lumen of
      pseudocyst results in pseudoaneurysm. The rupture of pancreatic pseudoaneurysm
      into the lumen of digestive tract causes massive bleeding witch source is often
      difficult to find during endoscopic examination. We present a case of patient
      with chronic alcohol pancreatitis, with pancreatic pseudocyst and of acute
      bleeding from upper digestive tract. In the endoscopy we found gastric ulcer with
      visible vessel. During hospitalization we observed increase the diameter of
      pseudocyst and circulation of it's liquid contence. Second-look endoscopy showed
      gastric fundic varices. Surgical operation revealed pseudoaneurysm of splenic
      artery inserting pressure on gastric wall.

PMID- 17007273
TI  - [Gastrointestinal stromal tumors of jejunum as a reason for bleeding of
      alimentary tract--case report].
AB  - We describe the case of a patient who was admitted to the ward because of
      bleeding from the alimentary tract. Both gastroscopy and colonoscopy did not
      permit to establish the reason of bleeding. The patient was qualified for
      laparoscopy. During laparoscopy the tumour as a reason of bleeding was found and
      removed from jejunum. The histopathological tests confirmed the diagnosis of low
      malignant gastrointestinal stromal tumours (GIST). We present in our paper the
      rules applying to dealing with GIST.

PMID- 17007274
TI  - [Non-Hodgkin extranodular lymphoma of the palate].
AB  - Non-Hodgkin lymphomas belong to the neoplasms of lymphoreticular system. They
      derive form lymphocytes or their precursors, and cells that form as a result of
      lymphocytes' transformation. In most cases, the extranodular localisation of the
      neoplasm is alimentary tract, particularly the stomach. Less frequent locations
      are the ovaries, kidneys, adrenal glands, caecum, anus area, and retroperitoneal
      space. Also the region of the head and neck, especially the salivary glands,
      eyeballs, naso-fauces, maxillary sinus, should be considered when talking about
      extranodular localization. However lymphomas in those regions rarely penetrate
      the orbital and cranial cavity. In very few cases non-Hodgkin lymphomas locate
      themselves in the fundus of the oral cavity and lips. The aim of the study is to
      present a patient with rarely occuring lymphoma of the soft palate. First
      complaints of pain have been noticed 3 months before the patient arrived in our
      hospital, and gradually intensified themselves, which caused problems during
      meals. The patient has lost 5 kg of weight since the beginning of the disease,
      and suffered from profuse night sweating. In local anaesthesia a biopsy specimen
      has been taken for histological examination. The result of the examination was:
      MALT lymphoma, CD20, CD3. The patient was qualified for chemotherapy according to
      CHOP scheme, in the Chair of Oncology of Medical University in Lodz. Next, the
      patient has been transferred to the Department of the Radiotherapy. The patient
      completed the treatment in good condition.

PMID- 17007275
TI  - [Acute lower gastrointestinal tract bleeding caused by Dieulafoy lesion in rectum
      -case report].
AB  - Dieulafoy lesion may be one of the rare causes of acute gastrointestinal (GI)
      bleeding. This pathology mostly appears in the stomach wall, but very rarely it
      can be found in other parts of GI tract. Authors describe a case of 57-year-old
      female patient with a history of ulcerative colitis, staying in the complete
      remission since the moment of diagnosis many years ago, without any treatment.
      During the week before admission to the hospital, patient observed streaks of
      blood in the stool and felt some pain in the lower abdomen. On the day of
      admission to one of surgical departments in Szczecin, acute rectal bleeding had
      started in the patient, causing very serious state. The primary diagnosis was:
      rectal bleeding caused by a flare of ulcerative colitis. Sigmoidoscopy was
      performed in Gastroenterology Departament and it showed a vessel coming out of
      the rectal wall (like Dleulafoy lesion), with symptoms of active bleeding, while
      the mucosa was unchanged. The hemoclipping was performed and bleeding has been
      stopped. There was no recurrent bleeding.

PMID- 17007276
TI  - [Statins in chronic heart failure--new indication?].
AB  - Chronic heart failure (CHF) is connected with very high risk of death. Discovery
      of neurohormonal mechanisms which contribute to pathogenesis of CHF changed
      therapeutic management of CHF. It was indicated that statins may exert beneficial
      effects in patients with CHF through preventing acute coronary syndromes,
      reducing myocardial hypertrophy, decreasing activation of renin-angiotensin
      aldosterone system and sympathetic system, inhibitory effects on inflammatory
      cytokines and metalloproteinases, improving endothelial function. Usefulness of
      statins in CHF is however controversial. There is some evidence that lower serum
      cholesterol concentrations relate to impaired survival in patients with CHF.
      Before data from large scale trials (CORONA, GISSI-HF, UNIVERSE) will be
      published, statin therapy in CHF must be recommended carefully.

PMID- 17007277
TI  - [Leptin--adipose tissue hormone and its role in cardiovascular diseases].
AB  - The discovery of leptin in 1994 led to research into the participation of that
      hormone in the development of many pathologic states. This article presents
      current knowledge on the role of leptin, in the pathogenesis of cardiovascular
      diseases. Leptin is a circulating peptide hormone produced by adipose cells which
      plays the main role in the regulation of metabolism in humans. Leptin, in the
      physiological range of plasma levels, is a regulator of cardiovascular function.
      In fact, higher plasma leptin levels as well as insulin resistance are directly
      correlated with adiposity. Hyperleptinemia accompanying obesity leads to many
      pathologic states: stimulation in platelets aggregation, tachycardia,
      hypertension, increases in plasma levels of pro-thrombotic factors and in levels
      of CRP and ET-1. In a multicenter study, hyperleptinemia turned out to be the
      main risk factor responsible for the ischemic disease, especially acute
      myocardial infarction. Elevated plasma leptin levels play a key role in increased
      incidence of cardiovascular mortality in obese.

PMID- 17007278
TI  - [Thrombinogenesis in chronic myeloproliferative syndromes].
AB  - Haemostatic disturbances are important in clinical complications in patients with
      chronic myeloproliferative syndromes and sometimes the reason of death.
      Pathogenesis of thrombo-embolic disease during these states is not clear. The aim
      of study was the evaluation of the risk of thrombosis in patients with chronic
      myeloproliferative syndromes using very detailed test to measure the
      concentration of TAT (thrombin-antithrombin) complexes. MATERIAL AND METHODS: The
      study was performed in 73 patients: in 22 with chronic myeloid leucaemia (CML),
      in 25 with polycythemia vera (PV), in 21 with essential thrombocytemia (ET) and
      in 5 with myelofibrosis (MF). The control group consisted of 29 healthy
      volunteers. In the blood plasma of studied persons concentration of TAT complexes
      and antithrombin (AT) activity were detected. RESULTS: We observed in patients,
      except MF, significant increase of TAT but diminished AT activity. CONCLUSIONS:
      Increased TAT complexes in chronic myeloproliferative syndromes is the evidence
      of significant thrombinogenesis. AT activity diminished in PV showes too high
      consumption of it with concomitant low synthesis.

PMID- 17007279
TI  - [Postparum thyroiditis].
AB  - Postpartum thyroiditis is one of the most common endocrinological disorders
      annually affecting millions of women world-wide. It is is defined as a syndrome
      of transient or permanent thyroid dysfunction occurring in the first year after
      delivery. A thyrotoxic phase of postpartum thyroiditis may be brief and unnoticed
      before a more long-lasting (permanent in up to 30%) hypothyroid phase occurs. The
      disease, found in approximately 5-10% of mothers in the general population, is an
      autoimmune disorder, and thyroid antibody-positive women in the first trimester
      have a 33% to 50% chance of developing thyroiditis in the postpartum period.
      Women suffering from other autoimmune conditions, or having a previous or family
      history of thyroid disease are at increased risk of its development. In this
      paper we present an overview of the pathogenesis, clinical aspects, diagnosis,
      and treatment options for postpartum thyroiditis with putting special emphasis on
      the results of recently published studies.

PMID- 17007280
TI  - [Sex hormones and adipocytokines in postmenopausal women].
AB  - Visceral fat accumulation occuring in postmenopausal women is connected with
      hypoestrogenism, decreased production of sex-hormone binding globuline (SHBG) and
      with rise in free testosterone. They have been identified as risk factors for
      cardiovascular diseases. The exact mechanisms mediating relationships between the
      excess of visceral adiposity, hormonal variations after menopause and metabolic
      disturbances, remain unknown. We speculate that adipocytokines produced by
      adipose tissue: adiponectin, leptin and resistin, might play a role. Adiponectin
      is a hormone which plays a role in insulin sensitivity and lipid oxidation, and
      possesses anti-inflammatory properties. Increased levels of androgens post
      menopause and low SHBG are connected with decreased production of adiponectin.
      Leptin is another of the adipocytokines which has been shown to be linked to
      insulin resistance, increased pressure and hypertriglyceridaemia. Sex steroids
      have effect on leptin secretion but the associations between leptin and menopause
      are controversial. Recently it was found that resistin, another bioactive
      substance produced by adipose tissue may related to insulin resistance. Studies
      on animals indicate that ovariectomy and testosterone significantly increased
      resistin expression. It seems that adipocytokines may be a link connecting
      postmenopasual hormonal changes, the excess of visceral fat and increased risk of
      cardiovascular diseases.

PMID- 17007281
TI  - [Clinico-pathological collations in borreliosis].
AB  - Borreliosis is an infectious disease caused by spirochetal microorganisms
      Borrelia burgdorferi transmitted by ticks. Due to versatile clinical
      symptomatology and many pathogenetic aspects not explained yet, diagnosis of this
      disease is often very difficult. Borreliosis may affect various human organs and
      systems such as movement system, nervous system (central and peripheral), skin,
      heart and vessels. One of the diagnostic methods for detection of microbial
      organisms in tissues is the histochemical staining by Warthin-Starry. Very
      important problem connected with this illness is the relationship between
      borrelial antigens and autoimmunity.

PMID- 17007282
TI  - [Alternations of bronchial smooth muscle and effect of therapy on remodeling in
      asthma].
AB  - Alternations in airway wall architecture, particularly increased smooth muscle
      mass are associated with pathogenesis of asthma. Muscle fiber hyperplasia and
      hypertrophy is a major contributor to the increase in smooth muscle mass. Airway
      smooth muscle was traditionally considered to have only contractile and
      proliferative functions and has little attention with regard to its ability to
      express and release inflammatory mediators. Airway smooth muscle cells have been
      shown to release cytokines such as: GM-CSF, IL-11, IL-6, IL-1, IL-5, IL-8, PGs
      and NO. Airway remodeling has been shown to respond to some degree anti
      inflammatory therapy. Several study results indicate that steroid can positively
      influence progressive airflow limitation. Combined use of a beta2-agonist and
      steroid can reduced the remodeling progression.

PMID- 17007283
TI  - [Glycosylated hemoglobin and left ventricular diastolic dysfunction in patients
      with type 2 diabetes mellitus].
AB  - Glycosylated hemoglobin (HbA1c) is a confirmed prognostic factor of
      cardiovascular complications in diabetic patients. The relative odds of
      cardiovascular disease (CD) increase by 20% for 1% increase of HbA1c above HbA1c
      5%. The aim of the study was to assess relationship between diastolic dysfunction
      and HbA1c in patients with diabetes mellitus 2 (DM 2) without critical coronary
      stenosis in coronarography. MATERIAL AND METHODS: The study comprised 57 subjects
      (35 men and 22 women) with DM 2, without coronary stenosis in coronarography,
      with normal and elevated HbA1c levels. The subjects were divided into two groups
      depending on HbA1c level: with HbA1c < or = 6.1% and HbA1c >6.1%. Parameters of
      left ventricular diastolic function were assessed in echocardiography according
      to criterions of European Society of Cardiology. Subjects with decreased systolic
      function (EF<50%) were excluded from the study. RESULTS: Diastolic dysfunction of
      the left ventricle was observed in 43% of patients with HbA1c >6.1% comparing to
      4.5% of patients in the group with HbA1 < or = 6.1%. In the group with HbA1c
      >6.1% in 38% of the patients abnormal relaxation in early filling phase and in 5%
      abnormal isovolumetric relaxation were observed. In the group with HbA1 < or =
      6.1% in only 1 patient (4.5%) abnormal relaxation in early filling phase was
      observed. CONCLUSION: Diastolic function of the left ventricle in patients with
      diabetes is dependent on HbA1c levels.

PMID- 17007284
TI  - [Evaluation of selected acute phase proteins in patients with metabolic
      syndrome].
AB  - Metabolic syndrome is a global epidemic problem. The latest studies revealed that
      metabolic syndrome can be associated with low-grade chronic inflammation which is
      postulated to play an essential role in the atherosclerotic process. The aim of
      the study was evaluation of selected acute phase proteins concentration in
      patients with metabolic syndrome. MATERIAL AND METHODS: 30 patients with
      metabolic syndrome were recruited to the study. The control group comprised 15
      healthy persons. In all subjects assessment of C-reactive protein (CRP), alpha1
      acid glycoprotein (AGP), alpha1-antichymotrypsin (ACT), ceruloplazmin (Cp),
      haptoglobin (Hp), alpha2-makroglobulin (alpha2-M), with use of rocket
      immunoelectroforesis method were performed. RESULTS: In the group with metabolic
      syndrome concentration of the studied acute phase proteins significantly exceeded
      those observed in the control group. Positive correlations between BMI, waist
      circumference and CRP ACT, AGP, Cp, Hp were found. CONCLUSIONS: Metabolic
      syndrome is associated with increased inflammatory process. Visceral obesity is
      an important determinant of low-grade inflammation in metabolic syndrome.
      Increased inflammatory process observed in patients with metabolic syndrome
      should be considered as a potential factor in atherosclerotic process.

PMID- 17007285
TI  - [Excessive body weight and coexisting with it changes in levels of hormones of
      adrenal and gonadal origin are associated with coronary artery disease in men].
AB  - The aim of study was to estimate relation between excessive body weight (EBW) and
      coronary artery disease (CAD) in men and to assess changes in concentrations of
      hormones due to EBW which may predispose to atherogenesis. MATERIAL AND METHODS:
      Study group (CADM) - 33 men in the age 52 +/- 6 years, with body mass index (BMI)
      above 25 kg/m2 and angiographically documented CAD. Comparative group (CM) - 13
      men in the same age without CAD. Apart from evaluation of occurence of risk
      factors in men of both groups concentrations of hormones in blood were assessed:
      insulin, insulin-like growth factor I, estradiol (E2), testosterone (T),
      dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone, luteinizing
      hormone, progesterone (Prog), cortisol (Cort) and leptin (Lept). RESULTS: In
      CADM, comparing to CM, greater values of parameters related to EBW, BMI (30,0 +/-
      2,6 vs. 26,8 +/- 2,6 kg/m2, p<0,0007) and waist-hip ratio (WHR 1,07 +/- 0,04 vs.
      0,92 +/- 0,03, p<0,000001), higher concentrations of Prog (3,0 +/- 1,3 vs. 1,4 +/
      0,9 nmol/l, p<0,0003), Kort (350 +/- 108 vs. 246 +/- 97nmol/l, p<0,006) and Lept
      (18,2 +/- 10,5 vs. 8,0 +/- 3,6 lU/l, p<0,0003) and lower of T (9,9 +/- 4,0 vs.
      12,3 +/- 3,2 nmol/l, p<0,046) were found. In regression analysis coexistence of
      EBW and eleveted level of Prog revealed the best fit with presence of CAD.
      Positive correlation between EBW and concentration of Lept and E2 and negative
      correlation between EBW and concentrations of T, Cort and DHEAS in CADM were
      found. CONCLUSIONS: EBW is a highly aggravating risk factor of CAD in men and is
      linked to proatherogenic changes in levels of steroid hormones of adrenal and
      gonadal origin.

PMID- 17007286
TI  - [Genetics analysis of microsatellite instability in patients from hereditary
      nonpolyposis colorectal cancer (HNPCC) families].
AB  - Microsatellite instability (MSI) is due to defective DNA mismatch repair and is
      characteristic of HNPCC tumours. THE AIM: The role of MSI in familial
      predisposition to colorectal cancer was investigated in this study by
      microsatellite analysis among familial cases. MATERIAL AND METHODS: PCR-based
      microsatellite analysis was performed in blood obtained from 30 members from
      HNPCC families. Blood samples age matched healthy individuals (n = 28) served as
      control. MSI was studied at five loci containing single- or dinucleotide repeat
      sequences and mapping to different chromosomal locations: BAT-25 (at locus 4q12),
      BAT-26 (2p16), D2S123 (2p16-p21), D5S346 (5q21-q22) and D17S250 (17q11.2-q12).
      RESULTS: MSI frequency was higher in member of HNPCC families (40%) than in
      control (10.7%) cases. Out of the 30 samples tested, 12 were found to be MSI
      positive, 9 MSI high and 3 MSI low. CONCLUSION: The present study suggest that
      microsatellite instability seem to be a risk factor of colorectal cancer in
      subjects belonged to HNPCC families with high incidence of this cancer.

PMID- 17007287
TI  - [Intentional self-poisonings among children and youth hospitalized in pediatric
      clinic].
AB  - The aim of the study was to identify the most important factors that can favour
      suicide attempts among children and to establish the age of highest risk, and
      note the extent of the phenomenon on the base of admissions to hospital within
      five years. MATERIAL AND METHODS: The research covered 42 patients of Paediatric
      clinic at the age of 12-17 years. Clinical intervention and observation,
      psychological evaluation and psychiatric examination were carried out. RESULTS:
      Fifty percent of the patients came of an incomplete (single-parent) families.
      Thirty one percents of patients' families were affected by alcoholism, nearly
      half of poisoned children were 14-15 years of age. There was a significant
      prevalence of girls in the group (88%). Seventeen percents of them had a history
      of multiple suicidal attempts. Children hospitalized by reason of intentional
      self-poisoning constituted, according to a year of observation, 0.45-1.34% (mean
      0,81%) of all patients of the Paediatric Clinic. CONCLUSIONS: Female sex and age
      of 15-16 years is a time of highest risk. Alcoholism is a frequent problem in
      families of children attempting suicide. Children with disturbed personality,
      behaviour and emotionality are particularly at risk of repeating an suicidal
      attempt and require longer psychological and psychiatrical care.

PMID- 17007288
TI  - [Concentration of interleukin 6 and 10 in tick-borne and purulend
      encephalomeningitis].
AB  - The aim of the study was to evaluate concentrations of interleukin 6 (IL-6) and
      interleukin (IL-10) in serum and cerebrospinal fluid (csf) of patients with tick
      borne encephalitis (tbe) and purulent meningitis before and after 4 weeks of
      treatment. MATERIAL AND METHODS: Group I consisted of 23 patients with tbe and
      group II - 16 patients with bacterial meningitis. Group III (control) consisted
      of 10 healthy men. RESULTS AND CONCLUSIONS: In patients with tbe and purulent
      meningitis concentrations of IL-6 and IL-10 in serum and csf were initially
      increased and tended to remain increased after 4 weeks of treatment. It suggests
      significant role of IL-6 and IL-10 in inflammatory process within cns. Higher
      concentrations of IL-6 than IL-10 in csf than in serum suggests their local
      synthesis within cns and tendency to the limitation of the inflammatory response
      to the intratecal compartment. Concentrations of both IL-6 and IL-10 in csf and
      serum remained sgnificantly higher in patints with purulent meningits than in
      tbe, both before and after treatment. This observation may be helpful in
      diagnosing the ethiology of meningitis and meningoencephalitis and monitoring the
      course of the disease.

PMID- 17007289
TI  - [Influence of digital subtraction cerebral angiography on blood flow in the
      middle cerebral artery].
AB  - The aim. Despite adhibition of new, improved enhancing agents some subjective
      signs during cerebral angiography are notified. This suggests that cerebral blood
      flow might be influenced by this procedure. The validity of transcranial color
      doppler sonography (TCCS) in cerebral blood flow evaluation is already proved and
      this method was selected for blood flow parameters estimation before and after
      cerebral angiography. MATERIAL AND METHODS: 33 subjects (17 female and 16 male)
      aged 50 +/- 13 were diagnosed by cerebral angiography. Before and immediately
      after angiographic examination cerebral blood flow parameters were evaluated in
      middle cerebral arteries by transcranial, sektor 2.5 MHz probe of Toshiba Aplio
      SSA 770A system. RESULTS: In comparison to pre-angiographic TCCS examination
      middle cerebral artery systolic velocity decreased about 3 cm/s (p<0.05). Mean
      and end-diastolic velocity in MCA insignificantly increased about 1 and 2 cm/s
      respectively (p>0.05). Impedance index values significantly decreased (Wilcoxon
      test, p<0.05) after angiography. CONCLUSION: Change of flow parameters in the
      middle cerebral artery prove increase of cerebral blood flow after diagnostic
      angiography.

PMID- 17007290
TI  - [Masked (atypical) depression in patients with back pain syndrome in outpatient
      neurological care].
AB  - Affective disorders, mainly depression is fast growing problem in highly
      civilised communities. The literature reports that 30-40% of patients seeking
      medical advice from specialists (not psychiatrists) in outpatient departments,
      suffer from these disorders. Many authors mention also diagnostic difficulties in
      dealing with atypical depression, and draw attention to the fact that this
      process is often "masked" by chronic pain. In neurological care we find a
      remarkable group of outpatients with back pain syndrome, mainly cervical and
      lumbar, with no corresponding lesions found on examination. This enabled us to
      assume that in some patients presenting with somatic symptoms and therefore
      referred to a neurologist, the reason of complaints can be depressive disorders.
      The aim of the study was to verify this hypothesis and to estimate the frequency
      of masked depression in neurological care. MATERIAL AND METHOD: 100 patients were
      examined in the neurological outpatient department, with the use of the two--Beck
      and Hamilton--scales of depression evaluation. RESULTS: A statistical analysis of
      the data thus obtained, showed that: back pain syndrome, as a symptom of
      depression, occurred in 14% of all patients referred to a neurologist, whereas in
      37%--depressive disorders, not diagnosed before, were detected; in 88,2% they
      were of mild and moderate type. CONCLUSION: In some patients presenting with
      somatic symptoms and therefore referred to a neurologist, the reason of
      complaints are depresive disorders.

PMID- 17007291
TI  - [The prevalence of intraarticular lesions in patients with active growth plate].
AB  - Anterior cruciate ligament (ACL) injuries are becoming increasingly prevalent in
      children and adolescents. In those who had undergone ligament injuries
      progressive meniscal damage is frequently observed. This, in turn, can lead to
      osteoarthritis in older age. The aim of the study was to assess the prevalence of
      ACL injury and/or other intraarticular lesions in patients with active growth
      plate. MATERIALS AND METHODS: 59 patients (30 girls and 29 boys) with an average
      age of 15.5 years (range 7-16 years) were included in the study. Thirty-nine
      injuries occurred during sports activities. Average time between knee trauma and
      surgery was 7,3 months (range 1 week-3 years). The relationships between meniscal
      and ligament injuries were analyzed by means of logistic regression. RESULTS: Of
      all 50 patients had meniscal tears (36 localized in the medial side) and 35 ACL
      tears. Both type of injuries occurred together in 26 patients. Three patients had
      undergone additional cartilage injury. We observed that in patients with ACL
      injury medial meniscus tear was found with higher frequency (20 knees, 57%) than
      lateral one (6 knees, 17%). Although meniscal tear was slightly higher
      distributed in boys (27/29) than in girls (23/30), sex appeared not to be the
      risk factor to knee injury. CONCLUSIONS: Anterior cruciate injuries are common in
      adolescents and have similar character to those observed in adults. Higher
      incidence of medial meniscus tear may be related to chronic anterolateral knee
      instability caused by delay in surgical treatment.

PMID- 17007292
TI  - [Quality of life in patients with hip bone fractures].
AB  - The aim of the study was to evaluate quality of life in patients who received
      surgical treatment of hip fracture. MATERIAL AND METHODS: Fifty patients (mean
      age: 77,5) including 37 women and 13 men participated in the study. All patients
      filled in a questionnaire constructed specially for the study. Patients were
      investigated three times: first time during hospitalization after surgery, second
      time within one month, and the last time after one year since surgery. Patients
      were not diagnosed as osteoporotic, before fracture had occurred. The diagnosis
      of osteoporosis was done on the basis of risk factors analysis and occurrence of
      low-energy fracture. RESULTS: Eight percent of patients assesed their economical
      status as very good before the hip fracture has occurred. There were no such
      assessments after the hip fracture. Before hip fracture 28% of patients' assessed
      their economical status as low, after hip fracture there were 50% of low
      economical status assessments. Twenty two percent of patients need continuous
      care after one year since hip fracture in comparison to 16% of patients before
      hip fracture. Twenty eight percent of patients who suffered from hip fracture
      assessed their health condition as bad, in comparison to 16% of such assessments
      before hip fracture. Eight percent of patients stated that their quality of life
      is low, in comparison to 40% of such assessments after one year since hip
      fracture. All patients declared that pain ailments increased during last year.
      Mortality rate in investigated group, despite immediate treatment, was 40%. In
      investigated group 40% of patients died within one year since hip fracture,
      despite immediate treatment. In group of patients who died within one year 54%
      assessed their quality of life as low. CONCLUSION: Quality of life assessment is
      important indicator of overall health condition and treatment efficiency.

PMID- 17007293
TI  - [Impacted morsellized bone grafting in primary total hip arthroplasty for
      acetabular protrusion in patients with rheumatoid arthritis].
AB  - Between 1991 and 2002, we performed 156 primary total hip replacements in
      rheumatoid arthritis patients with protrusion acetabulum. The deficient
      acetabulum was reconstructed with autologous and allogous morsellized bone grafts
      from the femoral head. MATERIAL AND METHODS: Group 1 were 26 patients with
      reconstruction acetabulum deficient with autologous morsellized bone grafts and
      group 2 were 10 patients in witch we use allogous grafts. All patients were
      reviewed at an average follow-up of 5 years. The function of operated hips was
      determining according WOMAC, HHS and Merle-d'Aubigne-Postela scores.
      Incorporation of grafts was assessing according to Avci criteria. RESULTS: We
      found similarly good and very good results in both groups. Incorporation of allo-
      and auto- bone grafts was observed after average 26 months. In 1 hip we found
      porotic grafts but without of loosening of the acetabular component. CONCLUSION:
      This technique is a good option in cases with protrusion acetabulum due to
      rheumatoid arthritis.

PMID- 17007295
TI  - [The role of melatonin in lipid peroxidation in healthy subjects].
AB  - Melatonin is naturally occurring hormone, synthesized in the pineal gland of the
      vertebrates. There were reports that it has an antioxidative properties connected
      with scavenging of reactive oxygen species. The aim of the study is to
      investigate the changes in the blood antioxidative activity and in lipid
      peroxidation after oral administration of small doses of melatonin. Melatonin was
      given for 2 weeks and the estimation of lenght of hormone therapy effect was
      carried out. MATERIAL AND METHODS: Venous blood was obtained from healthy
      volunteers (n = 20; 12 women and 8 men, aged 42 +/- 2), who were treated with 3
      mg melatonin per day. Blood was obtained before melatonin adminstration, on 7 and
      on 14th day of melatonin treatment, and on 10th day after last melatonin
      administration. The antioxidative properties were examined by FRAP method (ferric
      reducing ability of plasma) and concentration of lipids' peroxidation products
      were examined by reaction with thiobarbituric acid (TBARS). RESULTS: The higest
      plasma antioxidant activity was observed after 14 days of melatonin treatment and
      that increased level was maintained for the next 10 days after last dose of
      melatonin. The TBARS plasma concentrations reached the lowest level after 14 days
      of melatonin treatment and stayed the low level for 10 days after last dose of
      melatonin. CONCLUSION: It was estimated that oral administration of melatonin
      increases the plasma antioxidative properties and parallely decreases the process
      of lipids peroxidation. The biochemical changes were still observed on the 10th
      day of the end of melatonin treatment.

PMID- 17007294
TI  - [The G/C polymorphism of RAD51 gene in breast cancer].
AB  - The development of breast cancer is associated with an accumulation of specific
      genetic alterations. The aim. In this study the distribution of G/G, G/C and C/C
      genotype and frequencies of the G and C allele of RAD51 G/C polymorphism in women
      with breast cancer was examined. MATERIAL AND METHODS: 85 breast cancer samples
      were included in this study. They were categorised according to Scarf-Bloom
      Richardson criteria in women with breast cancer. Blood samples age matched
      healthy individuals (n = 91) served as control. RESULTS: The distribution of the
      genotypes of the G/C polymorphism RAD51 in both control and patients did not
      differ significantly (p>0.05) from those predicted by the Hardy-Weinberg
      distribution. There were no significant differences in the genotype distributions
      and allele frequencies between node-positive and node-negative patients.
      CONCLUSION: Our study implies that it is possible that the G/C polymorphism of
      the RAD51 gene may not be directly involved in the development and/or progression
      of breast cancer but further researches, conducted on larger population, are
      needed to clarify this point.

PMID- 17007296
TI  - [Thrombocytopenia and other extrahepatic manifeststions of hepatitis C virus
      infection--case report].
AB  - Authors present a case of forty seven years old woman with thrombocytopenia in
      the course of hepatitis C virus infection. Thrombocytopenia might be related to
      immunological mechanisms or be an effect of hypersplenism. Moreover mixed
      cryoglobulinemia, lymphocytic autoimmune thyroiditis with hypothyroidism and
      other laboratory abnormalities (impaired rate of lymphocytes CD4 to CD8, increase
      of B cells and natural killer cells, hypocomplementemia, hypergammaglobulinemia,
      increase of immune complexes concentration) were revealed. Above-mentioned
      abnormalities might be an effect of hepatitis C virus infection.

PMID- 17007297
TI  - [Haemangiopericytoma of the nasal cavity as a cause of recurrent epistaxis--case
      report].
AB  - A case of haemangiopericytoma of the nasal septum in 73-year-old female admitted
      to the Department of Otolaryngology of Wroclaw Medical University with a history
      of recurrent epistaxis and progressive right monolateral nasal respiratory
      obstruction is reported. On admission presented smooth, cyanotic, easily bleeding
      lesion in the nasal cavity on the right. Nose CT scans identified presence of a
      soft-tissue mass arising from the nasal septum. She was treated with a complete
      surgical resection of the mass. The diagnosis was established based on the
      careful histopathological examination. Haemangiopericytomas are rare soft-tissue
      neoplastic lesions, occurring mainly in adults, originating from pericytes and
      primarily arising in the lower extremities and retroperitoneum.
      Haemangiopericytomas of head and neck are very unusual and comprise about 15 to
      30%; of these, approximately 5% occur in the sinonasal area. Authors have
      presented etiology, symptomatology, histopathological features, differential
      diagnoses, diagnostic and therapeutic management. Malignant and benign clinical
      course have been described.

PMID- 17007298
TI  - [Markers of inflammatory process in stable and unstable coronary artery disease].
AB  - Clinical studies performed in last few years proved great role of inflammatory
      processes in development of atherosclerosis. Inflammatory markers indicating
      unstable atherosclerotic plaque were isolated. These biomarkers are used in
      diagnostics and identification of patients with unstable angina pectoris and
      miocardial infarct. Moreover usefulness of proinflammatory markers in indicating
      patients with high cardiovascular risk was confirmed. In result different markers
      of inflammation found their use in diagnostics of patients with stable and
      unstable coronary artery disease.

PMID- 17007299
TI  - [Incidentaloma--one of the greatest challenges of modern endocrinology].
AB  - Technological advance of the recent years has contributed to the development of
      the situation during which clinically inapparent masses are discovered in
      endocrine organs by high-resolution radiological imaging procedures that have
      been performed for other reasons. Most of these lesions, frequently referred to
      as incidentalomas, are clinically insignificant benign and hormonally inactive
      adenomas that neither pose a risk to a patient's health nor warrant the risks of
      further diagnosis and treatment. One of the greatest challenges of modern
      endocrinology is to distinguish the vast majority of clinically insignificant
      changes from other masses requiring further management such as hormone-secreting
      tumours and malignant lesions. Over the years a myriad of the diagnostic and
      therapeutic approaches has been recommended and presently there are still no
      uniform guidelines. The purpose of his article is to give an overview on the
      recent advances in diagnosis and management of pituitary and adrenal
      incidentalomas. We provide the reader with practical recommendations and
      underline areas in which further studies are required.

PMID- 17007300
TI  - [The role of matrix metalloproteinases and their tissue inhibitors in
      angiogenesis].
AB  - Cellular aspect of angiogenesis - the multilevel process involving the growth of
      new blood vessels from pre-existing vessels--includes migration and proliferation
      of the cells as well as remodelling of their environment--extracellular matrix
      (ECM). The key role in ECM remodelling is played by proteolytic enzymes
      classified as matrix metalloproteinases (MMPs). Recent research shows that
      performed by MMPs degradation of vascular ECM components is a significant event
      ocurring during angiogenesis. This process enables migration of endothelial cells
      that is crucial part in new vessel formation. MMPs also release sequestered
      angiogenic molecules, such as VEGF, bFGF and TGF-beta. Angiogenesis is a normal
      process in growth and development, as well as in wound healing, monthly
      reproductive cycle and during pregnancy. However, this is also a fundamental step
      in such conditions as malignancies, inflammation or ischaemia. The influence of
      MMPs on agiogenesis as terminal agents in many physio- and pathological events
      makes this group of enzymes very promissing aim of new therapeutic strategies
      based on modulation of angiogenesis.

PMID- 17007301
TI  - [The effects of amiodaron on the thyroid function].
AB  - The use of several groups of medications may result in thyroid dysfunction
      including thyrotoxicosis or hypothyroidism of various degree (from subclinical to
      full-clinical syndrome). The mentioned disturbances may develop either on the
      basis of normal euthyroid gland or may overlap the previously-existing oceult
      changes (first of all different forms of autoimmune thyroiditis). Amiodarone is a
      widely used anti-arrythmic drug with considerable potential to cause thyroid
      dysfunction because of its 35% iodine content. Besides amiodarone particles are
      known to inhibit T4 to T3 conversion, they work as inhibitors of nuclear
      receptors for thyroid hormones, exert cytotoxic effect and induce
      immune/inflammatory process in thyroid gland. Both thyrotoxicosis (AIT -
      amiodarone induced thyrotoxicosis) and hypothyroidism (AIH - amiodarone induce
      hypothyroidism) may develop during amiodarone therapy. AIT appears to occur more
      frequently in geographical areas with low iodine intake, whereas AIH is more
      frequent in iodine-sufficient areas. Two forms of AIT are known. Their
      differentiation is very important for further therapeutical procedures. Because
      thyrotoxicosis and hypothyroidism symptoms during amiodarone therapy are scanty,
      there is need for periodic determination of thyroid function. Normal ranges for
      amiodarone patients differ from those for the rest of population. They are
      presented in this review. Treatment of AIT is very complicated. Sometimes there
      is need to use few methods together, especially when amiodarone treatment can not
      be stopped.

PMID- 17007302
TI  - [Morgagni's hernia--still a difficult diagnostic problem].
AB  - Morgagni's hernia due to its non-specific symptoms and signs along with
      difficulties to detect it by x-ray imaging is still a disease difficult to
      diagnose. Patients suffering from this hernia are often treated unsuccessfully
      because of false diagnosis of other illnesses of the abdomen or thorax. It is
      only detailed diagnostics that can lead to a proper diagnosis. The authors
      present the current status of knowledge of Morgagni's hernia, its most common
      signs and symptoms and available diagnostic and therapeutic methods.

PMID- 17007303
TI  - [Laryngeal cancer risk factors].
AB  - Laryngeal cancer is the most common of head and neck cancers. Neoplasm used to
      develop basing on DNA mutation which leads to uncontrolled growth and cells'
      division. It is due to spontaneous mutations or influence of chemical, biological
      and physical factors. Laryngeal cancer generation is conditioned by many synergic
      factors. Some of them certainly participate in cancer genesis and this thesis is
      accepted by medical environment and other of them have been discussed giving
      different information. Definition of the risk factors role in laryngeal cancer
      etiology is very difficult especially regarding their contemporary occurrence in
      one person. Most common risk factors are environmental factors, gastroesophageal
      reflux, viral infections, diet, radiation, individual predisposition. Some of
      them, such as cigarette smoking and abuse alcohol are significantly oftener
      confirmed in patients with neoplasm diagnosis and others' role in developing of
      illness has been still researched. Thus the purpose of the study was to present
      so far achievements in laryngeal cancer etiology and to emphasize controversies
      relating to some factors' role in cancer genesis.

PMID- 17007304
TI  - [Gastroesophageal reflux disease in hazardous drinkers].
AB  - Excess alcohol consumption has been associated with multiple pathologies of the
      gastrointestinal tract. The consumption of large amounts of alcohol (hazardous
      drinking) facilitates acid regurgitation by reducing the pressure of the lower
      oesophageal sphincter and slowing both oesophageal motility and gastric emptying.
      Regardless of the type of alcoholic beverage involved lower alcohol doses also
      have been shown to induce decreased pressure in lower oesophageal, decrease in
      oesophageal motility and enhanced risk of gastroesophageal reflux disease (GERD).
      GERD can be important risk factor for oesophageal adenocarcinoma. For
      identification of hazardous drinking patients we can use AUDIT (Alcohol Use
      Disorder Identification Test). AUDIT has been created by World Health
      Organization experts as a simple screening test looking for hazardous drinking
      people.

PMID- 17007305
TI  - Taking the pulse of consumer-driven health plans.

PMID- 17007306
TI  - Consumer-directed health care: A panacea or the wrong prescription?

PMID- 17007307
TI  - Is the science of medicine trumping the art of medicine?

PMID- 17007308
TI  - Medical management on the bayou: one year after Katrina.

PMID- 17007309
TI  - Low patient satisfaction scores: the five stages of response.
AB  - When faced with poor patient satisfaction scores, emergency department physicians
      and medical directors have similar reactions. Ironically, the emotions
      experienced mimic the stages of grief.

PMID- 17007310
TI  - Tossing hand grenades: how to deliver feedback in medicine today.

PMID- 17007311
TI  - Cascading improvements in communication: adopting a new approach to
      organizational communication.

PMID- 17007312
TI  - Going solo in a group.

PMID- 17007313
TI  - What jobs will there be in the future?
AB  - Physicians often ask what kinds of jobs there will be for physician executives in
      the future. Learn what two futurists and four recruiters think about this issue
      in this excerpt from ACPE's recent book: A Career Guide for Physician Executives.

PMID- 17007314
TI  - Who owns health care's most valuable information?

PMID- 17007315
TI  - Do you want us to hide information or release information? Make up your mind.

PMID- 17007316
TI  - The government's war on health care fraud: what every physician executive needs
      to know.

PMID- 17007317
TI  - Making smart mistakes.

PMID- 17007318
TI  - Moving from resistance to support.

PMID- 17007319
TI  - Employers want to know, "what can you do for me"?

PMID- 17007320
TI  - All eyes on congressional elections.

PMID- 17007321
TI  - Ratcheting up quality reporting.

PMID- 17007322
TI  - A quest for better quality.

PMID- 17007323
TI  - Here's to your (mental) health.

PMID- 17007324
TI  - Striking a balance on new technology. When a health technology assessment guides
      patient management, health outcomes can improve significantly.

PMID- 17007325
TI  - Striking a balance on new technology. Cost-effectiveness analysis can help sort
      out emerging health care technologies, but what are the consequences for
      continued medical innovation?

PMID- 17007326
TI  - A sustainable solution.

PMID- 17007327
TI  - Analytics turn adversaries into allies.

PMID- 17007328
TI  - Outsourcing: better for the bottom line?

PMID- 17007329
TI  - The state of our health.

PMID- 17007330
TI  - EHR certification eliminates barriers.

PMID- 17007331
TI  - [Free-living amoebae as vehicles of pathogenic bacteria].
AB  - The free-living amoebae are ubiquitous organisms. They are found in humid soil
      and all water reservoirs, i.e. fresh, sea, freezing and hot water. They mainly
      feed on bacteria. Pathogenic properties of amoebae and the mechanisms underlying
      pathological changes induced during human infection have not yet been fully
      elucidated. They are the causative agents of primary amoebic meningo-encephalitis
      (PAM), granulomatous amebic encephalitis (GAE), a chronic progressive disease of
      the central nervous system, amebic keratitis (AK), a chronic eye infection;
      amebic pneumitis (AP), a chronic lung infection, and skin infection. Only a few
      isolates are strongly and permanently pathogenic to humans. Some isolates lose
      their pathogenic properties after one passage. It has been assumed that such
      "temporary", unstable pathogenic properties of the amoebae may be caused by
      internal factors carried by them. It is generally known that the free-living
      amoebae may be naturally infected with pathogenic bacteria, which have the
      ability to survive for a long time and to proliferate in the amoebae cells. The
      role of the amoeba in the process of maintaining, propagating and transmitting
      human pathogens has not been well recognized. It has been suggested that some
      infections can be acquired by inhaling aerosols containing amoebae cells filled
      with bacteria. The presence of bacteria inside the free-living amoebae possess a
      great challenge to organisations responsible for testing and inspecting the
      quality and cleanliness of surface waters, swimming pools and drinking water
      intakes.

PMID- 17007332
TI  - [Malaria and HIV co-infection].
AB  - The coexistence of malaria and HIV infection beyond inhabitants of sub-Saharan
      Africa, South America and South-East Asia arises a question whether there is an
      interaction between these two infections. This problem is extremely important in
      relation to pregnant women because of possibility of mother to child
      transmission. The available options are reviewed in the paper.

PMID- 17007333
TI  - [DNA microarrays in parasitology and medical sciences].
AB  - The article presents the current knowledge on the microarray technique and its
      applications in medical sciences and parasitology. The first part of the article
      is focused on the technical aspects (microarray preparation, different microarray
      platforms, probes preparation, hybridization and signal detection). The article
      also describes possible ways of proceeding during laboratory work on organism of
      which the genome sequence is not known or has been only partially sequenced. The
      second part of the review describes how microarray technique have been, or
      possibly will be, used for better understanding parasite life cycles and
      development, host-parasite relationship, comparative genomics of virulent
      organisms, develpoment vaccines against the most virulent parasites and host
      responses to infection.

PMID- 17007334
TI  - [Molecular techniques applied in species identification of Toxocara].
AB  - Toxocarosis is still an important and actual problem in human medicine. It can
      manifest as visceral (VLM), ocular (OLM) or covert (CT) larva migrans syndroms.
      Complicated life cycle of Toxocara, lack of easy and practical methods of species
      differentiation of the adult nematode and embarrassing in recognition of the
      infection in definitive hosts create difficulties in fighting with the infection.
      Although studies on human toxocarosis have been continued for over 50 years there
      is no conclusive answer, which of species--T. canis or T. cati constitutes a
      greater risk of transmission of the nematode to man. Neither blood serological
      examinations nor microscopic observations of the morphological features of the
      nematode give the satisfied answer on the question. Since the 90-ths molecular
      methods were developed for species identification and became useful tools being
      widely applied in parasitological diagnosis. This paper cover the survey of
      methods of DNA analyses used for identification of Toxocara species. The review
      may be helpful for researchers focused on Toxocara and toxocarosis as well as on
      detection of new species. The following techniques are described: PCR (Polymerase
      Chain Reaction), RFLP (Restriction Fragment Length Polymorphism), RAPD (Random
      Amplified Polymorphic DNA) and SSCP (Single Strand Conformation Polymorphism).

PMID- 17007335
TI  - Fish monogeneans from a shallow, eutrophic Oswin Lake in Poland.
AB  - BACKGROUND: A study was carried out in a shallow, eutrophic Oswin Lake, within
      Seven Islands Reserve (north-eastern Poland), in order to determine the infection
      of fish with monogeneans as sensitive indicators of water quality. This paper
      presents comparative analysis of the occurrence of Monogenea in fishes from two,
      distinctly separated pools of the lake, differing in environmental conditions.
      The impact of fish size and sampling season on the infection parameters was also
      analyzed. MATERIAL AND METHODS: In 1998 and 1999, a total of 1091 fish
      representing 8 dominant species were examined. Samples were collected four times
      a year (in May, July, August, and October) simultaneously from the eastern and
      western parts of the lake. RESULTS: 16 species of Monogenea (and some
      unidentified specimeus) occurred in the fish examined, most of them from the
      Dactylogyridae family: Dactylogyrus sphyrna, D. auriculatus, D. intermedius, D.
      anchoratus, D. falcatus, D. tincae, D. wunderi, D. zandti, D. difformis, D.
      nanus, D. distinguendus, D. crucifer, D. caballeroi. Furthermore, Tetraonchus
      monenteron (Tetraonchidae), Gyrodactylus elegans (Gyrodactylidae), and
      Paradiplozoon megan (Diplozoidae) were detected. Monogenea occurred abundantly on
      the gills of pike, roach, rudd, white bream, carp bream and crucian carp, but
      rather sporadically in tench and perch. The highest species variety and diversity
      of monogenean guilds were detected in carp bream and roach. It was proved that D.
      crucifer and D. difformis were significantly more abundant in the western pool
      compared to the eastern one. Infection of fish with Dactylogyridae was season
      dependent, contrary to the infection of pike with T. monenteron. Intensity of
      infection of white bream with D. sphyrna and roach with D. crucifer increased
      with fish body length; such a relationship did not appear for the other
      monogeneans and their hosts. CONCLUSION: Presence of common Monogenea in the fish
      examined, lack of rare species, poor diversity of monogenean guilds and
      relatively low infection rate could be connected with the low stability of the
      lake environment. Location-dependent occurrence of D. crucifer and D. difformis
      indicated that the exchange between fish groups from the eastern and western
      parts of the lake is limited.

PMID- 17007336
TI  - Parasites of carnivorous mammals in Bialowieza Primeval Forest.
AB  - BACKGROUND: Although the parasitofauna of wild carnivorous mammals in Poland is
      quite well recognized, there has been only one research carried on this issue so
      far in Bialowieza Forest--the last lowland primeval forest of temperate zone in
      Europe. MATERIAL AND METHODS: Twelve wild and two domestic species of carnivorous
      mammals are living in Bialowieza Forest. In our work faeces or intestines of all
      of them except ermine (Mustela erminea) have been examined and parasites or their
      eggs (or oocysts) recorded. In total 222 faecal probes from 13 species and 11
      intestines of weasels have been investigated. RESULTS: All species of examined
      carnivorous mammals were infected with parasites. The most infected species has
      occurred red fox Vulpes vulpes (over 70% infected with parasites) meanwhile only
      about 30% of otters Lutra lutra were infected. We found at least three protozoan
      species, one trematode, one tapeworm and nine species of nematodes. Except
      trematode Alaria alata, all of them are reported for the first time from
      Bialowieza Primeval Forest. Oocysts of coccidia have been found in faeces of nine
      host species, with the highest prevalence (29.4%) in badger. Six species of
      carnivorous mammals have been occurred infected with trematodes (highest
      prevalence 42.1% in wolves) and two with tapeworms (Diphyllobothrium latum with
      the prevalence 2.6% in otter and 31.6% in wolves). All examined host species were
      infected with nematodes (with prevalence from 14.7% in lynx to 72.7% in red fox).
      Results of our work should be treated as preliminary researches on the species
      composition of parasitic fauna invading carnivorous mammals in Bialowieza
      Primeval Forest.

PMID- 17007337
TI  - The gastro-intestinal parasites community of the Przewalski's horse, Equus
      przewalskii Poljakov, 1881, and the domestic horse in the Chernobyl exclusion
      zone.
AB  - A diagnostic deworming of 21 Przewalski horses, free-living in the Chernobyl
      exclusion zone Ukraine, and of six stabled domestic horses, has been conducted
      eighteen years after the Chernobyl nuclear disaster. This survey yielded 31
      species (of 5 families and 3 classes, 28 species of nematodes, 1 species of
      cestodes, and 2 larvae of botflies). A total 29 and 19 helmith species has been
      recorded in the Przewalski horse and domestic horse respectively. Only six
      helmith species were common for the two horse species. Species from the family
      Strongylidae constituted the dominant helmith group. Four cyathostomine species
      (Cyathostomum catinatum, Cylicostephanus minutes, C. longibursatus, Cylicocyclus
      nassatus) formed the majority of helmith parasites both in the Przewalski and
      domestic horses. The presently reported study revealed that Przewalski's horses
      keep their typical biological features and high resistance to parasitic
      infections. A substantial growth of heard was observed as well as good clinical
      health state of horses. This can be an argument favouring the use of Przewalski
      horses in re-naturalization of ecological disaster areas.

PMID- 17007338
TI  - Seasonal activity of the common European tick, Ixodes ricinus (Linnaeus, 1758),
      in the forested areas of the city of Olsztyn and its surroundings.
AB  - Common European ticks, Ixodes ricinus, have been found in forest areas situated
      within the boundaries of big cities, and in areas changed by anthropogenic
      pressure. Monitoring I. ricinus, in the areas used by the public for recreation
      and leisure, makes it possible to assess the risk of infection with the diseases
      they transmit. The objective of this study was the comparison of the seasonal
      activity of ticks, I. ricinus, in the afforested areas of the city of Olsztyn and
      its surroundings. MATERIAL AND METHODS: This survey was conducted at sites
      located in the afforested areas of Olsztyn and within the Warminski Forest
      situated about 15 km from Olsztyn. Ticks, I. ricinus, were caught every 10-14
      days from April to October 2001 by the commonly applied method of flagging.
      During each catch, the temperature (T) and relative humidity (%RH) was measured
      with a thermohygrometer, 1 m above the duff level. RESULTS: The tick population
      density at the Warminski Forest site was higher than that at the sites within the
      city limits (116.8 and 20.5 ticks per 100 m2, respectively). Two peaks of tick
      activity were recorded in this area--the spring peak in June and the autumn peak
      (much lower) in September. The activity of ticks in the afforested area within
      the city limits was much lower--only one (spring) peak occurred, which at most
      sites was observed in June. At all sites, included in the study, the peak
      activity of ticks was observed in April. CONCLUSION: The study suggests that the
      afforested areas outside the city are more dangerous to people than the area
      within the city because of the large number of ticks there.

PMID- 17007339
TI  - The use of gauze: will it ever change?
AB  - Although the benefits of healing in a moist environment have been published
      worldwide, the use of woven gauze as a wound contact material still prevails in
      many countries. This article traces the history of gauze and problems associated
      with usage against the introduction of one of the first modern materials, the
      hydrocolloid. Why this revolution in dressing material did not herald an
      immediate change of practice away from gauze is examined. Since the 1970s, the
      range, availability and sophistication of these and other moisture-retentive
      dressings have increased dramatically, and yet it seems that some practitioners
      remain unconvinced. The processes that underpin personal and organisational
      change that may contribute to this reluctance are also considered.

PMID- 17007340
TI  - Prediction and monitoring the therapeutic response of chronic dermal wounds.
AB  - A significant proportion of chronic wounds fail to heal in response to treatment
      of underlying pathologies combined with good wound care practice. Current
      prognostic tests to identify these wounds rely on the use of algorithms based on
      clinically measurable parameters such as wound dimensions and wound duration.
      Venous leg ulcers may be stratified into healing/non healing at 24 weeks of
      compression therapy and diabetic foot ulcer treatment outcome assessed using a 3
      parameter algorithm. Accurate and reproducible measurement of wound area is
      required for these algorithms to have clinical utility. Whilst a number of
      attempts have been made to develop computerised wound-assessment techniques,
      wound tracing by clinicians combined with planimetry remains the standard
      methodology. Once treatment has been initiated, it is important to continuously
      monitor the wound to assess efficacy of treatment. This can be achieved by
      measuring wound area change over the first weeks of treatment to identify whether
      re-assessment of treatment strategy is required. A number of algorithms for
      assessing rate of wound area change have been evaluated to determine a surrogate
      endpoint for healing. Retrospective analysis of large patient groups indicates
      that approximately 75% correct prediction of healing outcome can be achieved.

PMID- 17007341
TI  - Advances in the management of leg ulcers--the potential role of growth factors.
AB  - Venous ulcers are a major health problem because of the increased costs of the
      treatment and the refractory nature of the ulcers. The treatment cost is
      estimated to be around 1 billion dollars per year in the United States (US), and
      the average cost for one patient over a lifetime exceeds dollars 400,000. There
      has been an increasing trend in the use of growth factors in their management.
      Genetic engineering has revolutionised the research of wound healing, as the
      majority of recombinant growth factors are now available for in vitro and in vivo
      studies. Online searches of Medline, Pub Medical and Embase were carried out
      using the terms venous ulcers, leg ulcers, growth factors and growth hormone. The
      literature regarding the potential role of growth factors in the management of
      leg ulcers is reviewed. The important clinical studies are critically analysed
      with a view to appreciate the emerging therapies and the further research
      possibilities in the management of venous leg ulcers. Clinical results with the
      use of growth factors in non-healing wounds are encouraging. However, small
      sample sizes and inconsistent end points in different clinical studies have been
      the main hurdle in reaching a definite conclusion. Further research is needed to
      provide the definite evidence. Future developments may include different delivery
      methods for the growth factors, use of different combinations of growth factors
      administered simultaneously or, sequentially, bioengineered skin grafts and
      chemical induction of angiogenesis with the use of gene transfer techniques.

PMID- 17007342
TI  - The effect of various concentrations of human recombinant epidermal growth factor
      on split-thickness skin wounds.
AB  - Epidermal growth factor (EGF) is a potent stimulant of epithelialisation.
      However, topical application of EGF to achieve facilitated re-epithelialisation
      in partial thickness wounds has been controversial. A total of 10 pigs, each with
      eight 4 x 4 cm partial thickness wounds, were treated twice a day for 10 days to
      observe the effect of human recombinant EGF in concentrations of 0.1, 1, 5, 10,
      25 ug/g, vehicle only and two controls. The control and the vehicle-only wounds
      each demonstrated 100% healing time (HT100) of 9.31 +/- 1.34 and 8.5 +/- 1.12
      while the wounds treated with EGF ointment with concentrations of 0.1 (HT100 =
      6.4 +/- 0.71), 1 (HT100 = 5.2 +/- 0.63), 5 (HT100 = 5.8 +/- 0.85), 10 (HT100 =
      7.1 +/- 1.45) and 25 ug/g (HT100 = 7.4 + 0.57) demonstrated significant reduction
      in time to achieve re-epithelialisation. Among the EGF-treated wounds, the wounds
      treated with EGF concentrations of 1 and 5 ug/g achieved the fastest re
      epithelialisation with evidence of substantial increase in basal keratinocyte
      activity observed through Ki-67 activity. In conclusion, this article
      demonstrates the efficacy of human recombinant EGF in facilitating re
      epithelialisation of partial thickness wounds with the most efficient healing
      found in EGF concentrations of 1 and 5 ug/g.

PMID- 17007343
TI  - The management of wounds following primary lower limb arthroplasty: a
      prospective, randomised study comparing hydrofibre and central pad dressings.
AB  - Wound care following lower limb arthroplasty has not been subject to in-depth
      clinical research, primarily because such wounds usually heal without
      complication. However, when prosthetic implants are used, serious wound problems
      can be disastrous (Whitehouse et al. Infect Control Hosp Epidemiol 2002;23:183-9;
      Lindwell OM. Clin Orthop Relat Res 1986;211:91-103). We report the results of a
      prospective, randomised, controlled trial comparing a hydrofibre (Aquacel) and
      central pad (Mepore) dressing in the management of acute wounds following primary
      total hip or knee arthroplasty left to heal by primary intention. Dressing
      performance was measured in 61 patients receiving total hip or knee replacements.
      There was a significant reduction in the requirement for dressing changes before
      five postoperative days in the hydrofibre group (43% compared with 77% in the
      central pad group), and there were fewer blisters amongst patients in the
      hydrofibre group (13% compared with 26% in the central pad group). We conclude
      that there is a potential role for hydrofibre dressing in the management of
      arthroplasty wounds.

PMID- 17007344
TI  - Burn wound depth assessment--is laser Doppler imaging the best measurement tool
      available?
AB  - Accurate early assessment of burn wound depth is increasingly important in
      clinical decision-making. Clinimetric principles are absolutely mandatory while
      developing a new test or tool for use in the clinical setting. This article
      critically evaluates the clinimetrics of a powerful tool for assessment of burn
      depth and whether Laser Doppler Imaging can meet those criteria by virtue of
      differentiation between superficial and deep burns.

PMID- 17007345
TI  - Nocturnal sedation in a child with facial ulceration.
AB  - Mostly, herpes zoster affects adults and therefore childhood presentation can
      represent a diagnostic challenge. Childhood herpes zoster, when it occurs, can
      also be associated with peripheral nerve complications, as illustrated by this
      case. A 3-year-old child who had herpes zoster developed a nasolabial scar
      resulting in a shallow non-healing ulcer from being repeatedly picked. Healing
      was only achieved after nocturnal sedation, with chloral hydrate.

PMID- 17007347
TI  - [Liposome electrokinetic chromatography and its application in evaluating drug
      membrane interaction].

PMID- 17007346
TI  - [Advances in the study of the integrin alpha(v) beta3 antagonists].

PMID- 17007348
TI  - [Effect of preparation technique on in vitro release mechanism of huperzine A
      microspheres].
AB  - AIM: To investigate the effect of preparation technique on in vitro release
      mechanism of huperzine A-PLGA microspheres. METHODS: Huperzine A-PLGA
      microspheres were prepared by two kinds of O/O emulsion solvent evaporation
      method (method A and B). In vitro release mechanism was explained by release
      profile, degradation rate and swelling rate of microspheres in vitro. The
      microspheres morphology and drug distribution within microspheres were observed
      in order to explain further the drug release mechanism. RESULTS: The
      encapsulation efficiency of huperzine A microspheres prepared by method A and B
      was 47.60% and 83.50% respectively. Microspheres prepared by method A could
      sustain release for 35 days with nearly no initial burst release. The release
      profile fitted well to zero order equation and drug release mainly through
      degradation and diffusion mechanism. Huperzine A microspheres prepared by method
      B could sustain release for 21 days with some evidence of initial burst release.
      The release profile fitted well to the Higuchi equation and drug release was
      mainly through diffusion mechanism. CONCLUSION: Huperzine A microspheres prepared
      by method A had more desirable release profile.

PMID- 17007349
TI  - [Ester prodrug of scutellarin: synthesis, physicochemical property and
      degradation].
AB  - AIM: To establish the fundamentals for the design of scutellarin prodrug and
      formulation with feasible physicochemical and biopharmaceutical properties by
      esterifying scutellarin, an active component with poor absorption extracted from
      Erigeron breviscapus of Chinese medicine. METHODS: With the method of salifying
      followed by esterifying, ethyl and benzyl ester of scutellarin were synthesized.
      Glycolamide ester of scutellarin was also synthesized with an improved method.
      Their structures were confirmed by MS and 1H NMR. The solubility and partition
      coefficient of the prodrugs were determined and their degradations were
      investigated in various buffers and in human plasma. The emulsion and
      cyclodextrin complex of glycolamide ester were prepared and the protection of the
      ester from degradation was compared in the intestinal tract contents.
      Furthermore, the degradation of glycolamide ester in the homogenates of various
      intestinal segments was studied. Results Three prodrugs were synthesized
      successfully and their structures were confirmed. Glycolamide ester of
      scutellarin showed better stability in the aqueous solution (t(1/2) approximately
      =16 d, pH 4.2) and the shortest half-life in the human serum (t(1/2)
      approximately =7 min). Compared with scutellarin, the solubility of glycolamide
      ester was increased about ten times in pH 4.0 buffer, and about thirty five times
      in water. Partition coefficient of the glycolamide ester increased significantly
      from -2.56 to 1.48. However, the ester degradation in the homogenates of
      intestinal mucus would be an obstacle for its absorption. The degradation rates
      were in the order duodenum > ileum > or = jejunum > colon. The emulsion showed a
      better protection of glycolamide ester from the degradation than cyclodextrin
      complex. CONCLUSION: Glycolamide ester of scutellarin shows better
      physicochemical properties than ethyl and benzyl eater of scutellarin, but its
      stability in intestinal tract needs to be improved. The emulsion or / and colon
      targeted delivery may be selected as one of strategies to decrease the
      presystemic degradation.

PMID- 17007350
TI  - [Long-acting injectable microspheres of glucagon-like peptide-1].
AB  - AIM: To prepare glucagon-like peptide-1 (GLP-1) loaded long-acting injectable
      microspheres and to evaluate their in vitro release behavior as well as its
      pharmacodynamics. METHODS: GLP-1 loaded microspheres were prepared with poly
      (lactic-co-glycolic acid) (PLGA) as carrier materials by dowble emulsion (W/O/W)
      method. Physical and chemical characteristics of microspheres, such as mean
      diameter, morphology and drug loading were evaluated. The in vitro release
      behavior and its influencing factors were determined by HPLC, also the
      bioactivity of GLP-1 in the course of encapsulation process and in vitro release
      were evaluated by in vivo animal experiments. The effect of reducing plasma
      glucose about GLP-1 microspheres were evaluated on the diabetes mice. RESULTS:
      Microspheres with good shape and dispersive quality were prepared. The drug
      entrapment efficiency was more than 80%. The accumulated release in one month is
      up to 85% and the release equation is in accord with zero-class release model.
      The bioactivity of GLP-1 was conserved with glutin as inner water phase, but in
      the course of in vitro release, the specific activity of CLP-1 in the
      microspheres decreased a little. GLP-1 microspheres can decrease the plasma
      glucose significantly and the effect can go on for one month. CONCLUSION: GLP-1
      can be encapsulated in injectable microspheres to yield one-month continuous
      release when using biodegradable polymers PLGA as carrier material, and this
      technique will have a favorable perspective in the near future.

PMID- 17007351
TI  - Rapid purification of human albumin with immunomagnetic microsphere technology.
AB  - AIM: To develop a rapid and inexpensive method for purification of human albumin,
      a method of immunomagnetic microspheres (IMMS) based on enzyme-linked
      immunosorbent assay (ELISA) for the purification of human albumin from human
      serum. METHODS: Polystyrene magnetic microspheres with carboxyl groups as
      carriers were prepared, and then the carboxyl groups on the surface of the
      microspheres were activated by ethylcarbodiimide (EDC). Finally rabbit anti-human
      serum albumin (HSA) antibodies were covalently bound to it and the complex can
      specifically capture HSA. After the procedure of capturing HSA, through taking
      rabbit anti-human albumin protein antibodies as a capture antibody, and goat anti
      human albumin protein antibodies as a detection antibody, an ELISA on IMMS was
      developed, which can determine the recovery yield of HSA from the human serum.
      RESULTS: The result of the experiment was that the recovery of human albumin with
      IMMS was (86 +/- 4)%, and IMMS were reused for two other purifying cycles, the
      results of which were (69.0 +/- 0.6)% and (40.8 +/- 0.8)%, and the purity of the
      product was about 90%. CONCLUSION: The results above prove that the
      immunomagnetic purifiying strategy was shown to be efficient and offers an new
      thought for a large scale production of high-purity HSA.

PMID- 17007352
TI  - [Effect of hyaluronic acid chitosan-based microemulsion on the permeability of
      blood brain barrier in mice].
AB  - AIM: To study the effect of hyaluronic acid chitosan-based microemulsion (HAC-ME)
      on the permeability of blood brain barrier( BBB) by using Evans blue (EB) as the
      indicator. METHODS: A formamide extraction-ultraviolet spectrophotometry method
      was employed to determine the concentrations of EB in each of the tissues. The in
      vivo distribution of HAC-ME groups containing EB in mice and the fluorescence
      intensity and diffusion domain of brain slices were all studied. RESULTS:
      Contrasting to the common microemulsion (ME), HAC-ME at the lower concentration
      of HAC (<5 mg x mL(-1)) could further improve the transporting of EB across the
      BBB while EB concentration in other tissues decreased, and Tmax was delayed about
      30 min. CONCLUSION: HAC-ME could facilitate the transporting of EB across the BBB
      and it was concentration dependent. While the brain targeting absorptive
      capability of HAC-ME was enhanced.

PMID- 17007353
TI  - [Effect of baicalin on HSP70 expression of hippocampal neurons in focal brain
      ischemia-reperfusion injury rats].
AB  - AIM: To investigate the effect of baicalin on the hippocampal neuronal apoptosis
      and the expression of HSP70 in rats with focal brain ischemia-reperfusion injury.
      METHODS: One hundred and twenty male Wistar rats were randomly divided into six
      groups:sham operated group, ischemia-reperfusion group, nimodipine group and
      three baicalin groups,to which baicalin was administered at doses of 50, 100 and
      200 mg x kg(-1), separately. The models of focal brain ischemia-reperfusion
      injury induced by middle cerebral artery occlusion (MCAO) were used in this
      study. HE stain was used to observe the pathological changes. Flow cytometry
      (FCM) was used for determination of neuronal apoptosis. HSP70 protein expression
      of the neurons was detected with immunohistochemistry. Reverse transcription
      polymerase chain reaction (RT-PCR) was used to detect the expression of the mRNA
      level of HSP70. RESULTS: Baicalin can significantly relieve the pathological
      changes and inhibit apoptosis in hippocampus CA1 area, and at the same time
      increase the expression of HSP70 and HSP70 mRNA. CONCLUSION: Baicalin can relieve
      brain damage induced by focal brain ischemia-reperfusion in rats, which may be
      related to inhibiting the process of the neuronal apoptosis. The mechanism of
      antiapoptosis effect of baicalin may be related to the promotion of transcription
      of HSP70 mRNA and increasing the expression of the protein.

PMID- 17007354
TI  - [Resveratrol inhibits expression of EMMPRIN from macrophages].
AB  - AIM: To investigate the effect of resveratrol on EMMPRIN expression of
      macrophages. METHODS: Human monocytic cell line THP-1 cells were co-cultured with
      EMMPRIN-highly-expressed MCF-7 cells; MMP-9 production was assayed by zymography.
      THP-1 cells were induced by PMA, expression of EMMPRIN was assayed by Western
      blotting. Cells were treated with resveratrol or PPARgamma agonist--pioglitazone
      during differentiation, EMMPRIN expression and MMP-9 activity were assayed. U937
      cells were co-transfected with PPARy expression and luciferase-coding reporter
      vector, then cultured with pioglitazone or resveratrol, the activating capability
      of resveratrol on PPARgamma was evaluated by measuring the luciferase activity.
      THP-1 cells were pretreated with PPARgamma antagonist--GW9662 before pioglitazone
      or resveratrol treatment, then assayed for EMMPRIN expression and MMP-9
      production. RESULTS: EMMPRIN expression was greatly increased during the
      differentiation from monocytes to macrophages; co-culturing with MCF-7 cells
      significantly increased MMP-9 production by monocytes. Both resveratrol and
      pioglitazone markedly inhibited EMMPRIN expression during monocytes
      differentiation. Resveratrol significantly activated PPARgamma and GW9662 greatly
      decreased the effect of resveratrol on EMMPRIN and MMP-9. CONCLUSION: EMMPRIN
      expression is greatly up-regulated from monocytes to macrophages, which may play
      a role in inducing MMPs production by monocytes/macrophages. Resveratrol can
      significantly inhibit EMMPRIN expression via activating PPARgamma, which may be
      the underlying mechanism of its inhibitory effect on MMPs production by
      monocytes/macrophages.

PMID- 17007355
TI  - [Protective effect of tanshinones against liver injury in mice loaded with
      restraint stress].
AB  - AIM: To observe the protective effects of tanshinones (tanshinone IIA, tanshinone
      I, cryptotanshinone and dihydrotanshinone) against liver injury in mice loaded
      with restraint stress. METHODS: The liver injury model was established under 12 h
      restraint stress in mice 5 days after tanshinones treatment. The hepatoprotective
      effects were evaluated by assessing alanine aminotransferase (ALT) levels in
      plasma. The contents of vitamin C, GSH and malondialdehyde (MDA) in liver were
      performed by HPLC and TBARS methods, respectively. Oxygen radical absorbance
      capacity (ORAC) assay was used to measure the antioxidant capacity. RESULTS:
      Tanshinones decreased ALT and MDA levels, and increased ORAC, vitamin C and GSH
      levels in liver tissues as compared with restraint stress control. Tanshinones
      also significantly inhibited oxidation in vitro. Among four tanshinones,
      dihydrotanshinone was more effective than others both in vivo and in vitro test.
      CONCLUSION: Tanshinones possesses potent antioxidant activity in vitro and in
      vivo, and protected against liver injury induced by restraint stress. The active
      mechanisms may be related to their antioxidant capability.

PMID- 17007356
TI  - [Protective action of ulinastatin against lipopolysaccharides-induced acute lung
      injury in mice and the relation of it to iNOS and c-Jun expressions].
AB  - AIM: To study the protective action of ulinastatin against lipopolysaccharide
      (LPS)-induced acute lung injury in mice and the mechanism of its action. METHODS:
      Mice were intraperitoneally injected with ulinastatin (50 and 100 ku x kg(-1)) or
      saline at a period of 12 h, separately, 30 min after the last injection of
      ulinastatin, except normal control, all mice of other groups were injected a dose
      of LPS 15 mg x kg(-1) via tail vein. The levels of TNFalpha in serum and lung
      were measured by ELISA. The expression of TNFalpha mRNA and iNOS mRNA in lung was
      assayed by RT-PCR. The expression of c-Fos and c-Jun protein in lung was measured
      by Western blotting method. And the NO2- / NO3- level in serum and MDA in lung
      were measured with kits. RESULTS: The levels of NO2- / NO3- and TNFalpha in
      serum, MDA and TNFa in lung all increased after iv injection of LPS. The
      expressions of TNFa mRNA, iNOS mRNA, c-Fos and c-Jun in lung of LPS-injected mice
      were enhanced. Pretreatment with ulinastatin 100 ku x kg(-1) decreased the levels
      of NO2- / NO3- in serum and lung, reduced the index of lung, and inhibited the
      expressions of iNOS mRNA and c-Jun in lung induced by LPS in mice, while
      ulinastatin showed no effect on TNFa level in serum and lung. CONCLUSION:
      Ulinastatin protected mice from acute lung injury induced by lipopolysaccharides
      via inhibiting the activation of c-Jun and iNOS mRNA expression.

PMID- 17007357
TI  - [Desensitization of dust mite drops on antigen-specific asthmatic reaction in
      guinea pigs].
AB  - AIM: To establish an antigen-specific asthmatic model of guinea pig induced by
      protein antigen extracted from Dermatophagoides farinae (Der f), and study the
      desensitization of dust mite drops (DMD, extracted from Der f) in a dose
      progressive manner and long-term sublingual administration. METHODS: To sensitize
      the guinea pigs, the protein antigen emulsified in aluminium hydroxide gel was
      subcutaneously and intraperitoneally injected. To observe early-phase reaction of
      asthma, lung resistance (R(L)) and lung dynamic compliance (Cdyn) in the
      sensitized guinea pigs were determined by intravenously injecting antigen. To
      observe late-phase reaction of asthma, the sensitized guinea pigs were challenged
      with aerosolized antigen for 7 days. Subsequently, methacholine (Mch) in a
      cumulative dose-manner induced-airway hyperreactivity (AHR), inflammatory cells
      numbers in bronchoalveolar lavage fluid (BALF) and pathological changes of lung
      tissue were measured in the model. From the first day of sensitization, the
      guinea pigs in treatment group sublingually received DMD in a dose progressive
      manner. The model group sublingually received equivalent saline. The normal
      control group did not receive any treatment. RESULTS: The guinea pigs in model
      group showed a significant increase in R(L) and decrease in Cdyn, and developed a
      marked AHR to Mch. The number of total leukocytes and eosinophils increased
      significantly in BALF. Serious infiltration of eosinophils was observed in
      pathological section of lung tissue. Compared with model group, DMD treatment
      group exhibited a significant amelioration for early-phase and late-phase
      reaction of asthma. CONCLUSION: DMD in a dose progressive manner and long-term
      sublingual administration displays a significant desensitization on Der f antigen
      specific asthmatic reaction. The results provided experimental evidence for
      clinical therapy.

PMID- 17007358
TI  - Synthesis of a salacinol analogue and its alpha-glucosidase inhibitory activity.
AB  - AIM: To investigate more efficient synthetic method of the nitrogen analogue 4 of
      salacinol (1) for searching new antidiabetic agents. METHODS: The synthesis of
      the key intermediate 2, 4-O-isopropylidene-L-erythritol 1,3-cyclic sulfate (2a)
      was accomplished by modification of reports from D-glucose via seven steps in
      much more less expensive. Using this method, an efficient synthesis of 4 was
      carried out. The glycosidase inhibitory activity of 4 was tested for the
      intestinal alpha-glucosidase in vitro and compared with that of salacinol.
      RESULTS: A nitrogen analogue 4 of salacinol (1) was synthesized by the coupling
      reaction between the cyclic sulfate 2a and an azasugar 3b. CONCLUSION:
      Substitution of the sulfur atom in 1 with a nitrogen reduced the activity
      considerably.

PMID- 17007359
TI  - [Quantitative structure-activity relationship study of
      tetrahydroimidazobenzodiazepinone anti-HIV drug using three-dimensional
      holographic vector of atomic interaction field].
AB  - AIM: To study the quantitative structure-activity relationship ( QSAR) of 23
      tetrahydroimidazobenzodiazepinone (TIBO) as anti-HIV drug. METHODS: A newly
      developed three-dimensional holographic vector of atomic interaction field (3D
      HoVAIF) was used to describe the chemical structure of anti-HIV drug-23 TIBO, a
      partial least square regression (PLS) model was built. RESULTS: The obtained
      model with the cumulative multiple correlation coefficient (Rcum(2)), cumulative
      cross-validated (Qcum(2)) and standard error of estimation (SD) were Rcum(2) = 0.
      824, Qcum(2) = 0.778 and SD = 0.56, respectively. The model had favorable
      estimation stability and good prediction capabilities. CONCLUSION: Satisfactory
      results showed that 3D-HoVAIF with definite physic-chemical meanings and easy
      structural interpretation for structural characterization could preferably
      express information related to biological activity of TIBO.

PMID- 17007360
TI  - [A new sesqui-norlignan from Herpetospermum pedunculosum].
AB  - AIM: To study the chemical components from the bioactive extract of
      Herpetospermum pedunculosum, a Tibetan medicinal herb for liver diseases.
      METHODS: The isolation and purification of this extract were conducted by means
      of silica gels column chromatography and preparative HPLC. The structures of the
      compounds were elucidated based on their physical and chemical features, and
      spectral data. RESULTS: Two lignans were isolated from this extract. They were
      elucidated as herpetone (I), dehydrodiconiferyl alcohol (II). CONCLUSION:
      Compound I is a new compound with the rare structure of sesqui-norlignan.
      Compound II is isolated from the genus of Herpetospermum for the first time.

PMID- 17007361
TI  - [A IL-6R antagonist 2520A produced by a fungal species].
AB  - AIM: To isolate IL-6R antagonists from the cultured broth of the strain
      Torulomyces ovatus. METHODS: Various column chromatographyes were used to
      separate and purify the compounds with IL-6R antagonist activity. The spectral
      data and physic-chemical properties were measured for structure identification.
      RESULTS: One compound namely 2520 was isolated from the cultured broth of
      Torulomyces ovatus. CONCLUSION: 2520A is a known compound (ferrichrome). It is
      first reported about its antagonistic activity of IL-6R and identification of
      iron atom in its structure.

PMID- 17007362
TI  - [Interaction between strychnine and bovine serum albumin].
AB  - AIM: To study the interaction between strychnine and bovine serum albumin.
      METHODS: Fluorescence spectroscopy and ultraviolet spectroscopy were used.
      RESULTS: The static quenching and the non-radiation energy transfer are the two
      main reasons to leading the fluorescence quenching of BSA. The apparent combining
      constants (K(A)) between strychnine and BSA are 3.72 x 10(3) at 27 degrees C,
      4.27 x 10(3) at 37 degrees C, 4.47 x 10(3) at 47 degrees C and the combining
      sites are 1.01 +/- 0.03. The combining distance (r = 3.795 nm) and energy
      transfer efficiency (E = 0.0338) are obtained by Forster's non-radiation energy
      transfer mechanism. CONCLUSION: The interaction between strychnine and BSA was
      driven mainly by hydrophobic force.

PMID- 17007363
TI  - [Inclusion of coenzyme Q10 with beta-cyclodextrin studied by polarography].
AB  - AIM: To investigate the inclusion of coenzyme Q10 with beta-cyclodextrin (beta
      CD). METHODS: The inclusion of the electroactive guest molecule coenzyme Q10 with
      the host molecule beta-CD was studied by the polarography. The change of the
      reduction peak current of the inclusion complex with time and the change of the
      peak potential of the inclusion complex with beta-CD concentration were examined.
      In order to study the photostability, the change of the reduction peak current of
      both coenzyme Q10 and coenzyme Q10-beta-CD inclusion complex with time were also
      examined under light, separately. RESULTS: In 0.1 mol x L(-1) HAc/NaAc (pH 4.7)
      buffer-ethanol/water (60:40) medium, coenzyme Q10 was included with p-CD to form
      an 1:1 inclusion complex. The formation constant Kf was 1.26 x 10(4) L x mol(-1)
      the apparent formation rate constant was 6.64 x 10(-2) min(-1). The
      photodegradation apparent rate constant of coenzyme Q10 as 7.77 x 10(-3) min(-1)
      and that of the coenzyme Q10-beta-CD inclusion complex was 3.38 x 10(-3) min(-1).
      CONCLUSION: The inclusion of coenzyme Q10 with beta-CD took place. The stability
      of coenzyme Q10 to lights was improved in a certain degree due to the formation
      of the inclusion complex.

PMID- 17007364
TI  - [Structures of leucogen and its related substances in solution state].
AB  - AIM: To study the four diastereomers of leucogen and structure of the related
      substances. METHODS: LC-DAD, LC-MS/MS and LC- 1H NMR were used. LC was carried
      out with a Phenomnex Luna C18 (250 mm x 4.60 mm ID, 5 microm) column and a mobile
      phase of water-acetonitrile-glacial acetic acid (58:42: 0.3). RESULTS: The
      structures of leucogen and its related substances were identified. Leucogen and
      the related substances were found to have four diastereomers in solution state
      separately. The stability and transformation of the four diastereomers were
      analyzed and 3R4S5R was found to be more stable than the others according to
      quantum calculations. CONCLUSION: Leucogen have four diastereomers in solution
      state and it can transform from one diastereomer to the others, and the 3R4S5R is
      more stable than the others.

PMID- 17007365
TI  - [Pharmacokinetics of hylotelephin in Beagle dogs].
AB  - AIM: To investigate the pharmacokinetics of hylotelephin in Beagle dogs and
      obtain the main pharmacokinetic parameters. METHODS: An HPLC method with UV
      detection was developed to study the pharmacokinetics of hylotelephin in dogs by
      joining an internal standard (anthracene). Benzoyl chloride was used to the pre
      column derivatization of hylotelephin and methanol-water (64:36) was used as the
      mobile phase. According to the 3P97 pharmacokinetic program, the main parameters
      were calculated. RESULTS: The hylotelephin pharmacokinetics conforms to a two
      compartment open model after a single iv dose of hylotelephin 10.6 or 21.3 mg x
      kg(-1) in Beagle dogs. The parameters of two groups were as follows: T(1/2) alpha
      were 2.3 and 2.1 min, T(1/2) beta were 1.9 and 2.0 h, K12 were 0. 12 and 0.11
      min, K21 were 0.17 and 0.21 min, K10 were 0.011 and 0.0094 min, Vc were 0.54 and
      0.54 L x kg(-1), AUC were 1.8 and 4.1 g x min x L(-1), CL were 0.0048 and 0.0056
      L x kg(-1) x min(-1), MRT were 2.10 and 2.4 h, respectively. CONCLUSION: The
      pharmacokinetics of hylotelephin after iv administration showed a rapid
      distribution and elimination process in Beagle dogs and was of first order
      kinetics.

PMID- 17007366
TI  - [Determination of risperidone in human plasma by liquid chromatography-tandem
      mass spectrometry].
AB  - AIM: To develop and validate a liquid chromatographic-tandem mass spectrometric
      (LC-MS/MS) method for the determination of risperidone in human plasma. METHODS:
      Risperidone and the internal standard, diphenhydramine, were isolated from plasma
      by liquid-liquid extraction with etherdichloromethane (3:2, v/v) , then
      chromatographed on a Zorbax Extend-C18 column (150 mm x 4.6 mm ID, 5 microm)
      using a mobile phase consisted of acetonitrile-water-formic acid (40:60: 0.5,
      v/v), at a flow rate of 0.7 mL x min(-1). A Finnigan TSQ tandem mass spectrometer
      equipped with atmospheric pressure chemical ionization source was used as
      detector and was operated in the positive ion mode. Selected reaction monitoring
      (SRM) using the precursor product ion combinations of m/z 411-->191 and m/z 256-
      >167 were used to quantify risperidone and diphenhydramine (IS) , respectively.
      RESULTS: The linear concentration range of the calibration curve for risperidone
      was 0.025 - 50 microg L(-1). The lower limit of quantification was 0.025 microg x
      L(-1). The intra- and inter-day relative standard deviation (RSD) across three
      validation running over the entire concentration range was less than 7.1%. The
      accuracy was within +/- 3.8%. Each sample was chromatographed within 2.7 min.
      CONCLUSION: The method was proved to be rapid, sensitive and suitable for
      pharmacokinetic investigations of risperidone.

PMID- 17007367
TI  - [Allergic rhinitis in China].

PMID- 17007368
TI  - [Effect of Pranlukast on tissue remodeling in experimental guinea pig allergic
      rhinitis model].
AB  - OBJECTIVE: To explore the impact of Pranlukast in nasal mucosal remodeling in
      experimental allergic rhinitis. METHODS: Fourteen male guinea pigs were randomly
      divided into 3 groups: control group, ovalbumin (OVA) group and OVA + Pranlukast
      group. In the OVA group and OVA + Pranlukast group, OVA sensitized Hartley guinea
      pigs were exposured intranasally to OVA for a total of 12 weeks, the OVA +
      Pranlukast group received additional Pranlukast treatment from the second week to
      the 12th week. Paraffin embedded sections were stained with hematoxylin and eosin
      (HE), alcian blue-periodic acid-Schiff (AB-PAS), and Masson's Trichrome (MT).
      Infiltrating eosinophils, the number of goblet cells in the surface epithelium
      and gland cells in subepithelial nasal septal mucosa were counted. The damage of
      epithelium in nasal septum and extracellular matrix of nasal septal mucosa and
      conchae were determined. RESULTS: Compared with the control, the prolonged OVA
      exposure protocol caused significant pathological changes in the nasal mucosa,
      which included eosinophils infiltration into epithelium and submucosa (106.90 +/-
      13.66), significant goblet hyperplasia (22.05 +/- 5.81/mm), epithelial damage
      (intact epithelium: 47.25% +/- 7.67%) and deposition of extracellular matrix.
      These changes were significantly inhibited by Pranlukast, in which group, there
      were few eosinophils(8.95 +/- 2.32) , few goblet cells (5.73 +/- 1.07/mm), and
      relative intact epithelium (intact epithelium: 83.15% +/- 8.05%), and no
      significant ECM deposition. CONCLUSIONS: Early Pranlukast intervention could
      inhibit nasal mucosal remodeling in allergic rhinitis.

PMID- 17007369
TI  - [Mizolastine improves the quality of life in patients with perennial allergic
      rhinitis: a randomized, double blind, controlled study].
AB  - OBJECTIVE: To assess the effect of Mizolastine on quality of life (QOL) in
      patients with perennial allergic rhinitis. METHODS: A randomized, double-blind,
      placebo-controlled study was carried out with Mizolastine in sixty patients with
      perennial allergic rhinitis. QOL was measured by using the Medical Outcome Study
      Short-Form Health Survey (SF-36) questionnaire (Chinese version). Mizolastine (10
      mg once daily, 26 patients), Cetirizine (10 mg once daily, 22 patients) or
      placebo (12 patients) was given for 3 weeks. The SF-36 questionnaire was
      administered at the start of treatment and after 1 and 3 weeks of treatment.
      Symptom-medication scores were measured daily during the study. RESULTS: After
      the run-in period (baseline), there were no significant differences among the
      Mezolastine, Cetirizine and placebo groups in terms of symptoms or QOL scores.
      After 1 and 3 weeks of treatment, symptoms scores were significantly decreased
      and QOL scores significantly improved in the Mezolastine group and Cetirizine
      group in comparison with the placebo group ( both P < 0.001, chi2 test). All of
      the eight QOL dimensions were significantly improved (from P = 0.001 to P <
      0.0001, F test) after 1 and 3 weeks of Mizolastine treatment compared with
      placebo. There was no improvement in the placebo group. CONCLUSIONS: Mizolastine
      can not only decrease symptoms scores but also improve the QOL in patients with
      perennial allergic rhinitis. Placebo can relieve the symptoms but can not improve
      the QOL.

PMID- 17007370
TI  - [Characteristics of computed tomography of allergic fungal sinusitis].
AB  - OBJECTIVE: To sum up the characteristics of computed tomography of allergic
      fungal sinusitis (AFS) and to compare the CT changes with the findings in the
      operation. The diagnostic role of CT scan was discussed. METHODS: The CT scans of
      21 patients diagnosed as AFS were analyzed. The patients ranged from 15 to 50
      years old,there were 17 males and 4 females. The CT was scanned with both bony
      and soft tissue windows. The preoperative examinations included nasal endoscopy,
      skin prick test, total serum IgE and nasal secretion smear. The findings in the
      operation were compared with the preoperative CT scans. Histopathology and fungal
      smear were done postoperatively. RESULTS: Endoscopy showed that all patients had
      polyps with wasfy yellow or inspissated white secretion. Nine cases (11 sides)
      showed yellow-to-brown material similar to peanut butter in the nasal cavities.
      Nasal CT scan demonstrated unilateral lesion in 10 cases (10 sides) and bilateral
      lesions in 11 cases (22 sides), who were all pansinus diseases. CT scan
      demonstrated a sheet areas of high-attenuation like "ground glass" within sinuses
      coupled with soft tissue image around them. Bone erosion of anterior skull base
      was encountered in 3 cases (4 sides). One case showed the intracranial extension.
      Twenty cases had conceived nasal endoscopic sinus surgeries. One case underwent
      endoscopic sinus surgery combined with coronal approach. The yellow-to-brown
      material (allergic mucin) was detected in the cavities of 17 cases. Four cases
      had green-to-brown secretion like mud. After follow-up of 6 months to 7 years, 14
      cases were cured, 7 cases improved. Among them, 3 cases had to get revision
      surgeries because of recurrence 2 years after surgery. CONCLUSIONS: The
      characteristic of a sheet area of high-attenuation like " ground glass" within
      sinuses coupled with soft tissue image around them in computed tomography of
      nasal sinus, accompanied with invasive expansion or bone erosion, has a
      diagnostic significance for AFS.

PMID- 17007372
TI  - [Expression and localization of merlin in vestibular schwannoma].
AB  - OBJECTIVE: To clarify the expression and subcellular localization of merlin in
      vestibular schwannoma. METHODS: Fifty four paraffin embedded vestibular
      schwannoma samples confirmed by pathology after resection were included in the
      study. The expression of merlin in vestibular schwannoma was analyzed by
      immunohistochemistry. Nerve tissues that were resected during surgical treatment
      for trigeminal neuralgia and Meniere's disease were used as control. Western
      blotting was used to analyze the electrophoresis migration of merlin in the
      acoustic neuroma. Image analysis was used to calculate the positive expression
      percentage of merlin in each individual. The expression percentage of merlin in
      the tumor tissue was compared with age and gender of the patients, clinical
      course of the tumor, tumor growth index, tumor diameter and clinical stage.
      RESULTS: Merlin was expressed in 0 to 87.5% of the cells in vestibular schwannoma
      tissue with a mean of (46.66 +/- 5.75)%. There was a negative correlation between
      merlin expression percentage and tumor growth index. There were no correlations
      between merlin expression percentage and the age, gender, tumor diameter and
      clinical stage. There exists a difference for the location of merlin, mainly in
      the nucleus and perinucleus. There was also a cytoplasmic location. Merlin in the
      tumor tissue was shown by western blot to be in 65000 and 125000 positions.
      CONCLUSIONS: Merlin was expressed in vestibular schwannoma tissue, with a
      different intra-cellular location. Merlin might also exist as a complex with
      other proteins in the tumor tissue.

PMID- 17007371
TI  - [Patients suffered from enlarged vestibular aqueduct syndrome in Chifeng deaf and
      dumb school detected by Pendred's syndrome gene hot spot mutation screening].
AB  - OBJECTIVE: To investigate the incidence of hot spot mutation of PDS gene by
      genetic screening testing method in Chifeng City, Inner Mongolia. The feasibility
      and effectiveness of genetic screening method in finding enlarged vestibular
      aqueduct syndrome were confirmed by temporal bone CT scan. METHODS: DNA were
      extracted from peripheral blood of 141 students of Chifeng Deaf and Dumb school.
      PDS IVS7-2 A-G mutation, the most common PDS mutation in Chinese population, was
      analyzed by direct sequencing for PDS exon 7, exon 8 with intron 7. The
      individuals found with homozygous or heterozygous PDS IVS7-2 A-G mutation were
      given further temporal CT scan, ultrasound scan of thyroid and thyroid hormone
      assays. The results of PDS genetic screening and temporal bone CT scan were
      compared with each other. RESULTS: The sequencing results revealed twenty cases
      carrying PDS IVS7-2 A-G mutation, of whom nine cases were homozygous mutation and
      eleven cases were heterozygous mutation. Eighteen cases underwent temporal bone
      CT scan except two cases that left the school due to other health problem.
      Sixteen cases were confirmed to be enlarged vestibular aqueduct syndrome (EVAS)
      by CT scan and the shape and function of thyroid were clinically normal by
      ultrasound scan of thyroid and thyroid hormone assays, respectively. CONCLUSIONS:
      The patients suffered from EVAS can be diagnosed by the screening for the PDS hot
      spot mutation which has unique advantage in epidemiologic study in large scale
      deaf population. The preliminary data of this study suggested relatively high
      incidence of EVAS in Chifeng area.

PMID- 17007373
TI  - [Endonasal anatomy of lacrimal sac and its clinical significance in
      dacryocystorhinostomy].
AB  - OBJECTIVE: To explore the intranasal surface localization of the lacrimal sac in
      endoscopic dacryocystorhinostomy. METHODS: Fifteen adult cadavers (30 sides) were
      studied, the data of projection position of the lacrimal sac on the lateral wall
      of nasal cavity were measured. RESULTS: In 2/3 cadavers, the lacrimal sac is
      located above the axilla of the middle turbinate, and 1/3 lies below it. A
      majority of the lacrimal sac (2/3) are located below the entry point of the
      common lacrimal canaliculus, about 1/3 lies above it. Inner canthal ligament
      projects on the middle of the lacrimal sac, almost equal to the level of common
      lacrimal canaliculus. Thirty-two cases (thirty-nine sides) of chronic
      dacryocystitis were followed-up > 6 months after operation. Thirty-five sides
      were cured, 2 sides improved and 2 sides ineffective. The cure rate was 89.8%,
      improve rate 5.1% and ineffective rate 5.1%, respectively, and the total
      effective rate was 94.9%. CONCLUSIONS: The central position of
      dacryocystorhinostomy should be 0.2 cm above the front of the axilla of the
      middle turbinate, to make an curved mucous membrane incision 0.8 cm above and 0.
      4 cm below the front of the axilla of the middle turbinate and bone ostium about
      1.2 cm x 1.0 cm. It is the best position in endoscopic dacryocystorhinostomy.
      Locating the inner canthal ligament with a bayonet type forceps to find the
      projection of lacrimal sac is also a simple and easy method.

PMID- 17007374
TI  - [Effect of erythromycin on apoptosis of epithelial cell in nasal polyps].
AB  - OBJECTIVE: To study the effect of erythromycin on apoptosis and expression of Bax
      and Bcl-2 of epithelial cell in nasal polyps. METHODS: Epithelial cells from
      thirty nasal polyps and fifteen inferior turbinates were cultured in Dulbecco
      Eagle and Ham F12 (1:1) and divided into two groups (one group were treated with
      Erythromycin). Apoptosis was detected by terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling and expression of Bcl-2 and Bax detected by
      immunohistochemistry at 1, 3, 5 days after culture. RESULTS: The apoptosis
      indexes (AI) of epithelial cell in nasal polyps after cultured for 1, 3, 5 days
      with erythromycin were (33.23 +/- 6.50)%, (38.21 +/- 7.22)% and (52.63 +/- 7.86)%
      respectively. The AI of epithelial cell in inferior turbinates were (31.02 +/-
      5.60)%, (32.13 +/- 7.15)% and (39.64 +/- 7.48)% respectively. There was
      significant difference between two groups at 5 day after culture (P < 0.05).
      Expression of Bax and Bcl-2 of epithelial cell was significantly higher in nasal
      polyps than that in inferior turbinates (P < 0.01). Expression of Bax of
      epithelial cell cultured with erythromycin was significantly higher than that in
      the controls (P < 0.05). Apoptosis was clearly promoted after 5 day culture with
      Erythromycin (P < 0.05). CONCLUSIONS: Erythromycin promoted expression of Bax and
      apoptosis of epithelial cell in nasal polyps.

PMID- 17007375
TI  - [Intraoral submandibular gland excision and how to deal with external maxillary
      artery].
AB  - OBJECTIVE: To investigate the feasibility and safety of intraoral submandibular
      gland excision. METHODS: Analyze the relationship between the external maxillary
      artery and submandibular gland, and offer a reliable anatomical base for 10 cases
      of intraoral submandibular gland excision, including 8 cases of chronic
      sialadenitis, 1 case of pleomorphic adenoma and 1 case of cyst of submandibular
      gland. RESULTS: The external maxillary artery went across the surface of gland
      submandibular, and its branches provided nutrition for the gland in most cases.
      The results of 10 cases intraoral submandibular gland excision were effective and
      satisfied, without major complications. The average time of operation was 50
      minutes and the average hemorrhage of operation was 60 ml. CONCLUSION: Intraoral
      submandibular gland excision is safe and feasible for chronic sialadenitis and
      cyst of submandibular gland and some of benign tumor submandibular gland as long
      as indications strictly controlled and the external maxillary artery well coped
      with.

PMID- 17007376
TI  - [Diagnosis and treatment for the neck lump caused by migrating foreign body from
      the pharynx].

PMID- 17007378
TI  - [One case report of a laryngeal schwannoma].

PMID- 17007377
TI  - [Diagnosis of recurrent or residual nasopharyngeal carcinomas in the skull base
      area with F-18-fluoro-deoxyglucose positron emission tomography].
AB  - OBJECTIVE: To investigate the diagnostic value of F-18-fluoro-deoxyglucose
      positron emission tomography (FDG-PET) for the recurrent or residual
      nasopharyngeal carcinomas in the skull base area. METHODS: Nine post-irradiation
      nasopharyngeal carcinoma patients did FDG-PET scanning, CT/MRI imaging and
      underwent nasopharynx and skull base-biopsy under endoscopy. The results of FDG
      PET were evaluated and compared with CT/MRI studies and biopsies. RESULTS: In 9
      cases of post-irradiation nasopharyngeal carcinoma, CT/MRI detected 7 recurrent
      cases and 2 suspected recurrent cases in occipital bone and clivus. All 9 cases
      had accumulated FDG in nasopharynx and cranial base. A definite diagnosis was
      made by biopsy, 3 cases were confirmed recurrence, and others 6 cases were proved
      mucous chronic inflammation and (or) osteoradionecrosis. The accuracy of FDG-PET
      was 33.3% (3/9), and the false positive rate was 66.7% (6/9). CONCLUSIONS:
      Diagnosis of recurrent or residual nasopharyngeal carcinomas in the skull base
      area with FDG-PET had high false-positive rate, final diagnosis must depend on
      histopathologic examination under endoscopy.

PMID- 17007379
TI  - [Endoscope-assisted thyroidectomy with minimal incision in neck].
AB  - OBJECTIVE: To explore the feasibility of endoscope-assisted thyroidectomy with
      minimal neck incision. METHODS: Endoscope-assisted thyroid surgeries had been
      accomplished through incision above sternal notch and in submental area
      respectively from August 2003 to August 2005, including 11 partial lobectomy, 3
      lobectomy, 2 two-sides partial lobectomy, 1 isthmectomy. RESULTS: In this group,
      12 cases approached through above sternal notch, 5 cases approached through the
      submental area, and all were successful. The mean length of incisions was 2.3 cm
      (range from 1.5 cm to 3.0 cm). No one was converted to open surgery. The mean
      time of operation was 61.3 minutes (range from 30 minutes to 120 minutes). The
      mean volume of hemorrhage during the operation was 15.6 ml (range from 10 to 40
      ml). The mean volume of drainage of post-operation was 22.5 ml (range from 6 ml
      to 40 ml). The mean length of stay was 4. 5 days (range from 3 days to 6 days).
      There were no hoarseness and no low serum calcium. Following visits were
      performed after operation from 1 month to 12 months, and there were no stiff
      feelings on skin. The cosmetic outcomes of the incisions were good, except 1 case
      for scar physique. CONCLUSIONS: Endoscope-assisted thyroidectomy was safe and
      feasible with good cosmetic outcome. The selection of approach with minimal
      incision depends on the location of neoplasm.

PMID- 17007380
TI  - [Diagnosis and treatment of Madelung's disease].
AB  - OBJECTIVE: To review the characteristics of Madelung's disease which is rare and
      unfamiliar to clinicians and to find the method of diagnosis and treatment.
      METHODS: Detailed clinical data of 7 patients with Madelung's disease were
      reviewed and analyzed. And related literatures were discussed together. RESULTS:
      All of 7 patients have excessive subcutaneous fat deposit predominantly around
      neck. One patients had the complication of central and peripheral neuropathy, One
      patients had the complication of glucose intolerance, One patients had the
      complication of chronic hepatopathy and hyperuricaemia. These 3 patients were
      associated with sleep apnea syndrome simultaneously. Another one patient was
      accompanied by autonomic nervous system disease only. Total neck lipectomy and
      abstinence from alcohol were performed on 5 patients. No recurrence was seen
      during a follow-up of 6 months to 5 years. One patient received partial lipectomy
      twice and relapsed again. All pathological results were nonencapsulated fat. One
      patient refused treatment. Six men patients were alcohol abusers. CONCLUSIONS:
      Madelung's disease is characterized by massive accumulation of nonencapsulated
      subcutaneous fat mainly located symmetrically in the neck. Chronic alcoholism may
      be a major risk factor. It may be associated with some internal diseases. Total
      neck lipectomy to improve figuration and relieve pressure and abstinence from
      alcohol may be the main effective therapy.

PMID- 17007381
TI  - [Surgical approach for intrathoracic goiter].
AB  - OBJECTIVE: To explore the Surgical approach and management of intrathoracic
      goiter. METHODS: Seventy patients were operated on for thyromegaly extending to
      the thorax in an 15-year period at the department of Head and Neck surgery,
      Cancer Hospital, Chinese Academy of Medical Sciences. The median age of the 70
      patients (44 women and 26 men) was 55 years, with a range of 23 to 71 years.
      Sixty cases were benign intrathoracic goiter and ten cases were malignancy. To
      help choice of operative approach, the intrathoracic goiter was divided into
      three types to based on chest film, computed tomography or magnetic resonance
      imaging and clinical symptom. I type: the inferior extremity of goiter is on the
      aortic arch. II type is the goiter to enter intrathoracic and portion located
      behind aortic arch, or the goiter enter posterior mediastinum. For III type,
      intrathoracic goiter intrude thoracic cavity, or accompany superior vena caval
      syndrome. Operative method, surgical access and treatment effect were discussed
      in this essay. RESULTS: A cervical incision alone was performed in 62 cases (I
      type 41 cases, II type 21 cases), and sternotomy in 8 (II type 3 cases, III type
      5 cases). There was low morbidity and no deaths. Removal rate by cervical
      approach for intrathoracic benign and malignant goiter were 95% (57/60) and 50%
      (5/10) respectively. The Complication rate of cervical approach was significantly
      lower (8.1%) than that sternotomy approach (37.5%, P < 0.01). CONCLUSIONS: Most
      cases of intrathoracic goiter can be managed by cervical incision alone. Only a
      few cases, a median sternotomy approach may be needed when adhesions or an
      anomalous blood supply are present or carcinoma is suspected.

PMID- 17007382
TI  - [Regulation of nitric oxide-cyclic guanosine monophosphate pathway on cochlear
      sensitivity].
AB  - OBJECTIVE: To investigate the effect of nitric oxide (NO)-cyclic guanosine
      monophosphate (cGMP) pathway on cochlear sensitivity. Methods Ten groups of
      guinea pigs were treated with the following solutions by whole cochlear perfusion
      for 2 hours: (1) Artificial perilymph; (2) L-arginine; 93) Ca(2+)-ATPase
      inhibitor; (4) Ca(2+)-ATPase inhibitor + L-arginine; (5) Ca(2+)-ATPase inhibitor
      + cGMP; (6) Ca 2+ ATPase inhibitor + L-arginine + Non-selective NOS inhibitor;
      (7) eNOS inhibitor; (8) eNOS inhibitor + Ca(2+)-ATPase inhibitor; (9) eNOS
      inhibitor + Ca(2+)-ATPase inhibitor + L-arginine; (10) eNOS inhibitor + Ca(2+)
      ATPase inhibitor + L-arginine + nNOS inhibitor. The compound action potential
      (CAP) and cochlea microphonics (CM) were measured to assess the changes of
      cochlear sensitivity. After the perfusion, the cochleae were harvested and
      prepared for transmission electron microscopy. RESULTS: The average threshold
      shift of CAP after perfusion Ca(2+)-ATPase inhibitor was 28.5 dB, and it was
      improved in group 4 with 9 dB by L-arginine, similar with group 5. The threshold
      shift of CAP in group 8 was 42.5 dB, and it decreased in group 9 by L-arginine,
      on this foundation nNOS inhibitor was added, increased threshold shift of CAP was
      6.5 dB, similar with group 8. The results indicated that L-arginine could rivalry
      the role of Ca(2+)-ATPase inhibitor through the path of NO-cGMP. Transmission
      electron microscopy showed that Ca(2+)-ATPase inhibitor + L-arginine combined
      administration resulted in less vacuolization in out hair cell than that treated
      with Ca(2+)-ATPase inhibitor only. CONCLUSIONS: The NO-cGMP pathway could
      regulate cochlear sensitivity; L-arginine may improve the function of Corti's
      organ via nNOS, and they indicate an important role of supporting cells in the
      modulation of cochlear function.

PMID- 17007383
TI  - [Association of age-related hearing loss with mice which expressed only one copy
      of gene encoding NKCC1 co-transporter].
AB  - OBJECTIVE: To generate transgenic mice of NKCC1 +/- (heterozygous) and NKCC1 +/+
      (wild-type) that have a targeted disruption in the NKCC1 gene in order to
      investigate the relationship of one copy of NKCC1 gene (NKCC1 +/-) and age
      related hearing loss (AHL) and to study the possible pathogenesis of AHL METHODS:
      Auditory function of NKCC1 +/- mice was detected regularly by auditory brain
      response (ABR) and endocochlear potential (EP). Morphology of cochlea was
      observed by scanning electron microscope and content of NKCC1 protein was
      detected by Western blot. RESULTS: The mean value for ABR thresholds was elevated
      in NKCC1 +/- mice more than that of NKCC1 +/+ mice (P < 0.01). A progression of
      age-related hearing loss was found in NKCC1 +/- mice. Compared with younger NKCC1
      +/- mice, the mean value for ABR thresholds in aged NKCC1 +/- mice was
      significantly increased (P < 0.05). The EP of NKCC1 +/- aged mice was also
      significantly decreased more than that of the younger NKCC1 +/+ mice (P < 0.05).
      And content of NKCC1 protein were reduced with the growth of the age. The
      scanning electron microscope showed a kind of scattered punctiform absence of
      outer hair cells in elder NKCC1 +/- mice cochlea. CONCLUSIONS: NKCC1 gene maybe
      takes part in the pathogenesis of AHL. Mice that expressed only one copy of NKCC1
      could lead to AHL. AHL may be correlative with the amounts of NKCC1 protein and
      its function and also with the loss of outer hair cells perhaps.

PMID- 17007384
TI  - [Expressions and correlation with radiotherapy's effect of five kinds of genes in
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the expressions of E-cadherin, CD44H, matrix
      metalloproteinase-3 (MMP-3), nm23H1 and vascular endothelial growth factor (VEGF)
      in nasopharyngeal carcinoma and its relationship to the effect of radiotherapy.
      Furthermore, to analyze the predict value of radiotherapy effect. METHODS: The
      expressions of E-cadherin, CD44H, MMP-3, nm23H1 and VEGF in 62 patients with
      nasopharyngeal carcinoma were determined by immunohistochemical SP method. There
      were 62 patients (17 to 70 years old) with nasopharyngeal carcinoma which were
      treated by radiotherapy from March 1995 to October 1995 and the period of follow
      up had full 10 years. RESULTS: The expressions of CD44H (chi2 = 18.739, P =
      0.028) and VEGF (chi2 = 18.523, P = 0.030) were closely related with short-term
      effect after radiotherapy in nasopharyngeal carcinoma. The short-term effect was
      descent along with enhancement of their expressions. In the group of low
      expressions in CD44H and nm23H1, 3-year overall survival rate were 65.5% and
      45.5%, and 5-year overall survival rate were 47.3% and 22.7%. In the group of
      high expressions in CD44H and nm23H1, 3-year overall survival rate were 54.6% and
      75.9%, and 5-year overall survival rate were 27.8% and 53.2%. There were
      respectively significant difference between two group of expressions in CD44H
      (chi2 = 7.31, P = 0.0069) and nm23H1 (chi2 = 15.64, P = 0.0001). CONCLUSIONS:
      These findings indicated that to detect the expressions of CD44H and VEGF gene
      may predict short-term effect of radiotherapy. Furthermore, to detect the
      expressions of CD44H and nm23H1 gene may predict long-term effect of radiotherapy
      in nasopharyngeal carcinoma.

PMID- 17007385
TI  - [Research on lymphatic microvessel density and the relationship between it and
      lymphatic metastasis in human laryngeal carcinoma of type supraglottic].

PMID- 17007386
TI  - [Infant thyroglossal duct cyst presenting as a retropharyngeal and lateral
      pharyngeal abscess].

PMID- 17007387
TI  - [One case of posttraumatic cerebrospinal fluid rhinorrhea].

PMID- 17007388
TI  - [Three cases report of nasal polyps followed kidney transplantation].

PMID- 17007389
TI  - [One case of atypical carcinoid of larynx].

PMID- 17007390
TI  - [Specific sublingual immunotherapy of respiratory inflammatory diseases].

PMID- 17007391
TI  - Advanced chemical design with supported metal complexes for selective catalysis.
AB  - This review covers several recent topics of novel catalyst design with supported
      metal complexes on oxide surfaces for selective catalysis such as chiral self
      dimerization to create asymmetric oxidative coupling catalysis, surface
      functionalization with achiral reagents to promote asymmetric catalysis, and
      molecular imprinting to design shape-selective catalysis. The new concepts and
      designs find wide applications to a variety of selective catalysts.

PMID- 17007392
TI  - Design and solvothermal synthesis of luminescent copper(I)-pyrazolate
      coordination oligomer and polymer frameworks.
AB  - Two luminescent coordination compounds, [Cu(Pz)]3 (1) and [Cu2(Bpz)]n (2), were
      isolated from solvothermal reactions of Cu(NO3)2 with 3,5-dimethylpyrazole (HPz)
      and 3,3',5,5'-tetra-methyl-4,4'-bipyrazole (H2Bpz) respectively in the presence
      of NH3, of which 1 was revealed to be a planar trimer and 2 a three-dimensional
      framework, presenting a rare 3-connected binodal (6(2).10)(6.10(2)) topology and
      eight-fold interpenetration.

PMID- 17007393
TI  - Total synthesis of the macrocyclic cysteine knot microprotein MCoTI-II.
AB  - The first total synthesis of MCoTI-II, a cysteine knot microprotein and potent
      trypsin inhibitor, is described; a synthetic strategy has been developed that
      combines efficient backbone construction via optimised solid phase peptide
      synthesis with one-pot 'thia-zip' native chemical ligation and refolding to yield
      the natural product.

PMID- 17007394
TI  - Fluorescence quenching immunoassay performed in an ionic liquid.
AB  - We describe the first example of immunoanalysis performed within an ionic liquid
      with minimal deleterious effect; our results bode well for the development of
      second-generation biosensors, particularly in applications involving poorly water
      soluble analytes including pesticides, phospholipids, and illicit drugs.

PMID- 17007395
TI  - Reading the operation of an acid/base-controllable molecular switch by naked eye.
AB  - We report a pH-controllable molecular switch whose switching can be monitored by
      the naked eye; this system involves the formation of a complex between a
      [2]rotaxane--featuring dibenzylammonium and 4,4'-bipyridinium stations--and a TTF
      side-walled molecular clip.

PMID- 17007396
TI  - Metamagnetism in hydrophobically induced carboxylate (phenylmalonate)-bridged
      copper(II) layers.
AB  - Self-assembly of copper(l) ions, phenylmalonate and pyrimidine yields the layered
      compound [Cu(pym)(Phmal)n (1) where intralayer ferro- and interlayer
      antiferromagnetic interactions occur with three-dimensional antiferromagnetic
      ordering at T(c) = 2.15 K.

PMID- 17007397
TI  - Studies on the direct electrochemistry of hemoglobin immobilized by yeast cells.
AB  - The direct electrochemistry of hemoglobin can be achieved by immobilizing
      hemoglobin onto the surface of yeast cells through electrostatic attractions on a
      glassy carbon electrode.

PMID- 17007398
TI  - Biomimetic synthesis of marine sponge metabolite spiculoic acid A and
      establishment of the absolute configuration of the natural product.
AB  - The synthesis of spiculoic acid A (1) using a biomimetic Diels-Alder reaction is
      described; comparison of the specific rotation of the natural and synthetic
      material revealed that the enantiomer of the natural product has been
      synthesized.

PMID- 17007399
TI  - 2-D self-assembly of the bis(phthalocyaninato)terbium(III) single-molecule magnet
      studied by scanning tunnelling microscopy.
AB  - The presence of alkoxyl chains on the single-molecule magnet [(Pc')2Tb(III)] and
      its planar character favour its 2-D self-assembly on HOPG with the molecular
      plane parallel to the graphite surface, enabling us to control and/or predict the
      orientation of the preferential magnetization axis on the surface.

PMID- 17007400
TI  - Reversible lithium insertion and copper extrusion in layered oxysulfides.
AB  - All of the copper in the layered oxysulfides Sr2MnO2Cu1.5S2 and Sr2MnO2CU3.5S3
      may be extruded as the element and the copper ions replaced quasi-reversibly by
      lithium ions in reductive topotactic ion exchange reactions; dramatic changes in
      magnetic properties result.

PMID- 17007401
TI  - Ionic liquids enable electrospray ionisation mass spectrometry in hexane.
AB  - Addition of a lipophilic ionic liquid to non-polar, hydrocarbon solvents (such as
      hexane and toluene) permits electrospray ionisation mass spectrometric analysis
      of dissolved analytes.

PMID- 17007402
TI  - 2,2'-Disubstituted F12binaphthyl derivatives: stannanes, boranes, and (R)
      F12BINOL.
AB  - 2,2'-Distannyl derivatives of dodecafluorobinaphthalene are converted to a novel
      D2 symmetric borane dimer, which can be oxidized to (+)-F12BINOL; resolution
      using (S)-acetoxypropanoyl chloride affords enantiopure material.

PMID- 17007403
TI  - Balancing framework densification with charged, halogen-bonded-pi-conjugated
      linkages: [PPh4]2{[E-TTF-I2][Re6Se8(CN)6]} versus [PPh4]2[EDT-TTF-I]2{[EDT-TTF
      I][Re6Se8(CN)6]}.
AB  - The ionic character of a set of two redox linkages and strong, directional
      halogen bonding at the organic-inorganic interface compromise to produce two
      materials sharing a common two-dimensional net, eventually extended in a third
      dimension, although two of the six symmetrical halogen bond acceptors ultimately
      remain uninvolved as a result of charge densification.

PMID- 17007404
TI  - Stereoselective polymerization of rac- and meso-lactide catalyzed by sterically
      encumbered N-heterocyclic carbenes.
AB  - New sterically encumbered N-heterocyclic carbene catalysts were synthesized and
      used to polymerize rac-lactide to give highly isotactic polylactide or meso
      lactide to give heterotactic polylactide.

PMID- 17007405
TI  - Rapid synthesis of diketopiperazine macroarrays via Ugi four-component reactions
      on planar solid supports.
AB  - Libraries of diketopiperazines have been generated in high purity using the small
      molecule macroarray synthesis platform.

PMID- 17007406
TI  - Sulfamides and sulfamide polymers directly from sulfur dioxide.
AB  - SO2 gas is effectively used for the preparation of N,N'-diarylsulfamides and
      shape-persistent sulfamide polymers, which utilize a network of intermolecular N
      H...O=S hydrogen bonds to self-assemble into soft porous materials.

PMID- 17007407
TI  - Gold as intermolecular glue: a predicted planar triaurotriazine, C3Au3N3, isomer
      of gold cyanide.
AB  - It is predicted that solid gold cyanide, AuCN, could have an alternative infinite
      trigonal-sheet crystal structure, of almost the same energy as the known
      hexagonally-packed infinite-chain structure.

PMID- 17007408
TI  - Tin-free radical alkylation of ketones via N-silyloxy enamines.
AB  - The radical alkylation of ketones is achieved by their conversion into
      corresponding N-silyloxy enamines, followed by a radical reaction with alkyl
      halides bearing electron-withdrawing groups.

PMID- 17007409
TI  - A mild and convenient synthesis of N-carbobenzyloxy ketimines.
AB  - N-Carbobenzyloxy (Cbz) ketimines were prepared conveniently from N-Cbz amines by
      oxidation with N-tert-butylbenzenesulfinimidoyl chloride.

PMID- 17007411
TI  - Enantioselective synthesis of alpha-terpineol and nephthenol by intramolecular
      acyloxazolidinone enolate alkylations.
AB  - Enolate anions generated from norterpenyl bromides bearing oxazolidinone chiral
      auxiliaries at the chain termini underwent efficient, stereo-biased cyclizations
      to form 6- and 14-membered rings in novel synthetic routes to alpha-terpineol and
      nephthenol enantiomers.

PMID- 17007410
TI  - Dendrimer-assisted low-temperature growth of carbon nanotubes by plasma-enhanced
      chemical vapor deposition.
AB  - Using a shielded growth approach and N2-annealed, nearly monodispersed Fe2O3
      nanoparticles synthesized by interdendritic stabilization of Fe3+ species within
      fourth-generation poly(amidoamine) dendrimers, carbon nanotubes and nanofibers
      were successfully grown at low substrate temperatures (200-400 degrees C) by
      microwave plasma-enhanced chemical vapor deposition.

PMID- 17007412
TI  - Regulation of alpha-chymotrypsin activity on the surface of substrate
      functionalized gold nanoparticles.
AB  - A gold nanoparticle functionalized with substrates for alpha-chymotrypsin was
      fabricated to afford an enzyme modulator that exhibited enzyme-specific
      activation coupled with general inhibition of other proteases.

PMID- 17007413
TI  - Inhibition of C(2)-H/D exchange of a bis(imidazolium) dication upon complexation
      with cucubit[7]uril.
AB  - Inclusion of the alpha,alpha'-bis(3-(1-methylimidazolium))-p-xylene dication in
      cucurbit[7]uril (CB[7], K(CB[7]) = (4.3 x 10(9) M(-1)), with C-H...O=C hydrogen
      bonding between the guest C(2)-protons and the carbonyl oxygens of the host
      portals, inhibits the H/D exchange for the C(2)-proton with k(OD) (25 degrees C,
      D2O) decreasing from 1.2 x 10(3) M(-1) s(-1) (pKa = 22.3) in the absence of CB[7]
      to 0.9 M(-1) s(-1) (pKa = 25.4) in the presence of 1.1 equiv. CB[7].

PMID- 17007414
TI  - Fabrication of zeolite-4A membranes on a catalyst particle level.
AB  - Zeolite-4A membranes are coated onto spherical Pt/gamma-Al2O3 particles with an
      average diameter of 1.5 mm, and a model oxidation reaction of a mixture of CO and
      n-butane (50 : 50) is used to demonstrate the concept of reactant selectivity via
      the coated defect-free membranes.

PMID- 17007415
TI  - Facile routes to alkyl-BIAN ligands.
AB  - The Alkyl-BIAN ligands tert-Butyl-BIAN and 1-Adamantyl-BIAN have been synthesized
      and their structures have been determined by single-crystal X-ray diffraction
      along with that of the ZnCl2 complex of tert-Butyl-BIAN.

PMID- 17007416
TI  - An efficient and highly stereoselective synthesis of new P-chiral 1,5
      diphosphanylferrocene ligands and their use in enantioselective hydrogenation.
AB  - An efficient and highly stereoselective synthesis of P-chiral 1,5
      diphosphanylferrocene ligands has been developed, and the introduction of P
      chirality in ferrocene-based phosphine ligands enhances the enantioselective
      discrimination produced by the corresponding catalyst when matching of the planar
      chirality, the chirality at carbon and the chirality at phosphorus occurs.

PMID- 17007417
TI  - Rapid phosphorus triester hydrolysis catalyzed by bimetallic tetrabenzimidazole
      complexes.
AB  - Bimetallic complexes based on the binucleating ligand N,N,N',N'-tetrakis[(2
      benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane (1L) and its new toluoyl
      ester derivative (2L) catalyze the hydrolysis of phosphorus triesters at ambient
      temperature with activities rivalling the fastest known systems.

PMID- 17007418
TI  - Encoding calamitic mesomorphism in thermotropic lanthanidomesogens.
AB  - Peripheral cyanobiphenyl dendrimers impose a microphase organization compatible
      with smectic mesomorphism, in which the bulky nine-coordinate lanthanide core is
      located between the decoupled mesogenic sublayers made up of parallel
      cyanobiphenyl groups.

PMID- 17007419
TI  - Mild hydrolysis of nitriles by Fusarium solani strain O1.
AB  - High levels of an aromatic nitrilase (about 37 microkat/L culture) were induced
      in Fusarium solani O1 after transfer of the mycelium from a rich medium into a
      medium with 20 mmol/L picolinonitrile. The mycelium was entrapped in lense-shaped
      particles consisting of a polyvinyl alcohol/polyethylene glycol copolymer
      (LentiKats). The cell-free extract was immobilized by hydrophobic binding onto a
      Butyl Sepharose column. The enzyme was useful for the mild hydrolysis of
      nicotinonitrile, isonicotinonitrile and benzonitrile.

PMID- 17007420
TI  - Use of the industrial yeast Candida utilis for cadmium sorption.
AB  - The sorption ability of Candida utilis biomass for cadmium ions with accumulating
      competence of dried cells and cells in alginate was compared. After an
      optimization of process conditions (pH 5.5, biomass concentration 1 g/L and c0 50
      mg/L), the cadmium sorption capacity of dried yeast biomass was perceptibly
      higher than that of the other tested adsorbents. Considering the sorption of the
      dried yeast biomass equal to 100 %, the cells in alginate reached 86 % while
      native cells showed only 42 %.

PMID- 17007421
TI  - Xyn11A, a multidomain multicatalytic enzyme from Pseudobutyrivibrio xylanivorans
      Mz5T.
AB  - The rumen bacterium Pseudobutyrivibrio xylanivorans Mz5T has a potent xylanolytic
      enzyme system. A small native peptide (approximately 30-kDa, designated Xyn11A)
      from the bacterium was first isolated and characterized by Edman degradation. The
      gene coding for Xyn11A was identified using PCR amplification with consensus
      primers. It was then fully sequenced to reveal an open reading frame of 1809 bp.
      The predicted N-terminal domain exhibited xylanolytic activity and was classed to
      the family 11 of glycosyl hydrolases; it is followed by a region with homology to
      a family 6 cellulose binding module. The C-terminal domain codes for a putative
      NodB-like polysaccharide deacetylase which is predicted to be an acetyl esterase
      implicated in debranching activity in the xylan backbone. As similar domain
      organization was also found in several other xylanases from a diverse range of
      bacteria, a common ancestor of such a xylanase is considered to be present and
      spread, possibly by horizontal gene transfer, to other microorganisms from
      different ecological niches.

PMID- 17007422
TI  - Interference of Salmonella enteritidis and Lactobacillus spp. with IL-8 levels
      and transepithelial electrical resistance of enterocyte-like Caco-2 cells.
AB  - Caco-2 cells (exhibiting characteristics of mature villus enterocytes) were used
      to determine bacteria (Salmonella enteritidis causing human gastroenteritis)
      intestinal cell interactions. The interference of bacteria with the
      transepithelial electrical resistance (TEER) of filter-grown Caco-2 cells and the
      production of IL-8 after exposure of the cells to S. enteritidis 857 and/or
      Lactobacillus strains (L. gasseri LF221 and L. rhamnosus BGT10) was evaluated.
      The strain 857 decreased TEER of filter-grown Caco-2 cells; in contrast,
      lactobacilli had a little or no effect. The effect of S. enteritidis on the TEER
      decreased if Caco-2 cells were pre-incubated with lactobacilli. This strain
      induced high levels of IL-8 (which can lead to cell damage). Compared to the IL-8
      synthesis after exposure of Caco-2 cells to S. enteritidis 857, simultaneous
      exposure of Caco-2 cells to S. enteritidis and lactobacilli inhibited the IL-8
      synthesis after short recovery periods.

PMID- 17007423
TI  - Differentiation of anaerobic polycentric fungi by rDNA PCR-RFLP.
AB  - The suitability of restriction fragment length polymorphism (RFLP) analysis of
      the ribosomal DNA cluster for discriminating two genera of anaerobic polycentric
      fungi, Orpinomyces and Anaeromyces, was determined. Three PCR-amplified DNA
      fragments--nuclear small subunit (SSU; 18S rDNA), the nuclear large subunit (LSU;
      28S rDNA) and internal transcribed spacer (ITS)--were restricted with
      endonucleases AluI, DraI, HinfI and MboI. Although the SSU DNA fragment could be
      restricted successfully by all four enzymes, no differences were observed between
      restriction patterns of Orpinomyces and Anaeromyces. The most polymorphic
      restriction pattern between Orpinomyces and Anaeromyces resulted from cleavage of
      LSU rDNA fragments cut by AluI and HinfI and ITS fragment cut by DraI and HinfI.
      Genus-specific RFLP patterns were determined for Orpinomyces and Anaeromyces
      genera; the results showed that the PCR-RFLP analysis of rDNA offers an easy and
      rapid tool for differentiation of two polycentric genera of anaerobic fungi,
      which could be hardly separated on the basis of morphology.

PMID- 17007424
TI  - Effect of oregano essential oil on chicken lactobacilli and E. coli.
AB  - The effect of the oregano essential oil (EO) on lactobacilli and E. coli isolated
      from chicken was showed in the series of in vitro and in vivo experiments.
      Minimum inhibitory concentrations of amikacin, apramycin, streptomycin, neomycin
      against E. coli strains increased after oral application of EO.

PMID- 17007425
TI  - Effect of lactobacilli on E. coli adhesion to Caco-2 cells in vitro.
AB  - Inhibitory effect of various lactobacilli against pathogenic strains of E. coli
      in model system Caco2 cells was determined by enumerating the number of adhering
      E. coli after pre-incubation (exclusion), post-incubation (displacement) or co
      incubation (competition) with lactobacilli. Porcine E. coli strain F107 (F18ab,
      Stx2v) in the competition assay with porcine lactobacillus strain P10 gave
      bacterial counts 7.25 (log CFU per well); in the exclusion test it was only 7.05
      while in displacement test it reached 7.29. The lowest E. coli counts adhering to
      Caco-2 cells were in exclusion assay (pre-incubation, Lactobacillus inoculated as
      the first). Pre-treatment of E. coli with our lactobacilli strains reduced the
      cultivable E. coli numbers.

PMID- 17007426
TI  - Spreading and mutability of Selenomonas ruminantium plasmids.
AB  - Two small plasmids from Selenomonas ruminantium strain 19D were cloned in
      Escherichia coli and completely characterized. Sequence comparison indicated that
      the plasmids are similar to those reported in genetically vaguely related S.
      ruminantium strain S20. Small 1.4-kb plasmids pSRD191 and pONE430 are only
      distantly related (approximately 30 % for deduced Rep protein amino acid
      sequence) but possess a short highly conserved region outside rep gene. Larger
      plasmids pSRD192 and pONE429 possess large identical DNA regions in an otherwise
      dissimilar background. Recombination is proposed as an important mechanism of
      evolution and spreading of S. ruminantium plasmids.

PMID- 17007427
TI  - Effect of gluten-free diet on microbes in the colon.
AB  - The effect of gluten-free diet (GFD) and chitosan was evaluated in healthy
      individuals; GFD remarkably influenced the structure of the gut bacterial
      population and its metabolism. Administration of GFD and chitosan (3 g daily)
      significantly changed composition and metabolism of the bacterial population.
      Chitosan stimulated the counts of fecal chitinolytic bacteria and decreased the
      body mass of treated persons.

PMID- 17007428
TI  - Effect of fatty acids on growth of conjugated-linoleic-acids-producing bacteria
      in rumen.
AB  - Microorganisms with high activity of linoleic acid delta12-cis,delta11-trans
      isomerase were isolated from the digestive tract of ruminants and characterized.
      The isolate with the highest isomerase activity was identified as
      Pseudobutyrivibrio ruminis. The susceptibility of this strain to 3 fatty acids
      added to the grow medium was determined. A significant inhibition of bacterial
      growth (during a 3-d period) by linoleic acid (0.1 %) and oleic acid (5 ppm) was
      observed; no inhibition was found in the presence of stearic acid.

PMID- 17007429
TI  - Diet-dependent shifts in ruminal butyrate-producing bacteria.
AB  - The influence of a host's diet on Butyrivibrio and Pseudobutyrivibrio populations
      was investigated by competitive PCR. Specific primers were designed and
      competitive PCRs developed for both groups. Results (from 4 cows with different
      diets) suggested that high-fiber intake essentially increases the Butyrivibrio
      amounts in the rumen, whereas high-energy food additives lead to its suppression.
      The Pseudobutyrivibrio concentration also changed during the experiment but
      without any significant relation to the host's diet.

PMID- 17007430
TI  - Limited genetic variability in Megasphaera elsdenii strains.
AB  - Levels of phenotypic and genotypic diversity among seven Megasphaera elsdenii
      strains recovered from rumen contents of cattle, sheep and lambs were determined
      by a combination of antibiotic-resistance analysis and PCR fingerprint techniques
      targeted both to the ribosomal RNA operon (ARDRA, RISA) and the whole genome
      (ERIC-PCR, RAPD-PCR). Despite exhibiting different antibiotic resistance
      profiles, the tested strains represent genetically nearly identical isolates.
      Close genetic relatedness was found among M. elsdenii isolates that originated
      from vastly different habitats worldwide, as revealed by the comparison of 16S
      rDNA sequences.

PMID- 17007431
TI  - New species of rumen treponemes.
AB  - Three strains of rumen treponemes were isolated and partially characterized. The
      strains differed significantly one from another in morphology, fermentation
      characteristics and plasmid profiles. Their genetic variability was assayed using
      DNA-based molecular approaches. Easily differentiated ARDRA (amplified ribosomal
      DNA restriction analysis) patterns indicated that the strains represent different
      bacterial species.

PMID- 17007432
TI  - Effect of chitosan on the growth of human colonic bacteria.
AB  - Growth of 6 bacterial strains representing dominant members of the human colonic
      microflora was measured in the presence of 0.025, 0.05 and 0.5 % chitosan (from
      shrimp shells, with a 97 % final degree of deacetylation). The effect of chitosan
      was variable and dependent on bacterial species. The most susceptible to chitosan
      were bacteria belonging to genera Bacteroides and Clostridium (91-97% growth
      inhibition). On the other hand, Roseburia sp., Eubacterium sp. and
      Faecalibacterium sp. were more resistant (63-83 % inhibition of growth). Chitosan
      can thus be considered as one of the means for influencing the bacterial
      population in the human colon.

PMID- 17007433
TI  - Activity and cellular localization of amylases of rabbit cecal bacteria.
AB  - Five 11-week-old rabbits, fed a commercial granulated feed, were slaughtered and
      cecal starch-degrading bacteria enumerated; total concentration of cultivable
      bacteria utilizing starch averaged 5.5 x 10(10) CFU/g. The activity and cellular
      localization of amylases was determined in 9 bacteria identified as Actinomyces
      israeli (strains AA2 and AD4), Bacteroides spp. (strain AA3), Dichelobacter
      nodosus (strain AA4), Mitsuokella multiacidus (strain AA6), Eubacterium spp.
      (strains AA7 and AB2), Clostridium spp. (strains AD1 and AA5). Four strains (AA3,
      AA4, AA5, AD4) produced extracellular amylases with an activity of 26-35 micromol
      of reducing sugars per h per mg of protein; in five strains (AA2, AA6, AA7, AB2,
      AD1) amylases were membrane-bound with an activity of 14-18 micromol of reducing
      sugars per h per mg of protein. All strains exhibited a low intracellular
      amylolytic activity. The pH optimum of amylases was 6.8-7.0. In strains producing
      extracellular amylases a substantial loss of viscosity was observed during
      incubations of cultivation supernatant with starch, similar to viscosity
      reduction in starch solutions treated with alpha-amylase; this indicates an endo
      type (random cleavage) of extracellular amylase reaction in the bacteria under
      study. No strain possessed glucoamylase activity.

PMID- 17007434
TI  - Amiloride resistance in the methanoarcheon Methanothermobacter
      thermoautotrophicus: characterization of membrane-associated proteins.
AB  - An amiloride-resistant mutant with diminished Na+/H+ antiporter activity was
      isolated from Methanothermobacter thermoautotrophicus. To define the protein
      basis of amiloride resistance, the composition of membrane-associated proteins
      was partially characterized and compared with that of the wild type strain. An
      abundant 670-kDa membrane-associated protein that was present only in the mutant
      strain was analyzed by MALDI-TOF MS and identified as a coenzyme F420-reducing
      hydrogenase. The amiloride resistance was not accompanied by changes in protein
      size or changes in the level of subunits A or B of the A1A0-type ATP synthase; on
      the other hand, the SDS-PAGE patterns of the chloroform-methanol extract of
      membranes from both strains were different. Two bands with calculated molecular
      mass 16 and 11 kDa were identified as MtrD and AtpK, respectively. The observed
      over-expression of a 22.7-kDa protein in the mutant cells may represent the
      multimeric form of the MtrD subunit. These results show that the impairment of
      the Na+/H+ antiporter system in the amiloride-resistant mutant of
      Methanothermobacter thermoautotrophicus is accompanied by only small changes in a
      few membrane-associated proteins.

PMID- 17007435
TI  - Mercuric reductase gene transfer from soil to rumen bacteria.
AB  - Conjugal transfer between soil bacterial population and microorganisms isolated
      from the rumen of herbivores from mercury-polluted area was investigated. The
      transfer of merA encoding mercury-resistance plasmids from soil bacteria
      Enterobacter cloacae and Enterococcus durans into two ruminal isolates
      Citrobacter freundii and Bacillus subtilis was observed. Approximately the same
      frequency of mobilization in mating experiments was observed for both Gram
      negative (approximately 2.5 x 10(-8), transconjugants-to-recipient ratio) and
      Gram-positive (approximately 1.3 x 10(-8)) bacteria.

PMID- 17007436
TI  - Different utilization of glucose and raffinose in Bifidobacterium breve and
      Bifidobacterium animalis.
AB  - Growth of 2 strains of Bifidobacterium breve and 4 strains of Bifidobacterium
      animalis was evaluated with glucose, raffinose or a mixture of glucose and
      raffinose as substrates. All strains of B. animalis and one strain of B. breve
      grew more slowly on glucose than on raffinose or the mixture of glucose and
      raffinose; one strain of B. breve grew more rapidly on the mixture of glucose and
      raffinose than on raffinose while 2 strains of B. animalis grew faster on
      raffinose than on the mixture of raffinose and glucose. Both strains of B. breve
      utilized glucose and raffinose simultaneously. In contrast, all strains of B.
      animalis strains displayed atypical growth with rapid utilization of raffinose
      followed by slow utilization of glucose. The cell morphology of all strains of B.
      animalis was affected by the sugar used for cultivation: tiny and rather
      spherical cells were observed on glucose while on media with raffinose the cells
      were large and had the species-specific shape. Description of preferential
      utilization of various saccharides by bifidobacteria can contribute to the
      development of new synbiotic preparations and new cultivation media for
      bifidobacteria.

PMID- 17007437
TI  - Distribution of bifidobacteria in the gastrointestinal tract of calves.
AB  - Development of gastrointestinal microflora of calves with special reference to
      bifidobacteria was investigated; fecal bacteria were enumerated in calves aged 3
      days to 7 weeks. Bacteria were detected by using selective media, bifidobacteria
      using modified TPY agar with an addition of mupirocin and acetic acid and by
      fluorescence in situ hybridization (FISH). Bifidobacteria were dominant group of
      fecal flora of calves after 7 d of life, constituting 10 % of total bacterial
      counts. The highest bacterial concentrations were observed in rumen, cecum, and
      colon, the lowest in abomasum and duodenum. Bifidobacteria and lactobacilli
      exhibited the highest survival ability during stomach passage and dominated in
      all parts of the digestive tract. Bifidobacteria counts determined by FISH were
      significantly higher than those provided by cultivation. Modified TPY agar was
      highly selective and suitable for bifidobacteria isolation but FISH was shown to
      be a more precise method for their enumeration. Our results show that
      gastrointestinal microflora of calves in the milk-feeding period is similar to
      breast-fed infants with respect to the occurrence of bifidobacteria as a dominant
      bacterial group. The use of Bifidobacterium strains offers a promising way for
      providing beneficial effectors for calves in the milk-feeding period.

PMID- 17007438
TI  - Identification of Arcobacter species using phospholipid and total fatty acid
      profiles.
AB  - High-performance liquid chromatography (HPLC) and gas chromatography-mass
      spectrometry (GC-MS) were used to analyze the phospholipids and fatty acids of
      four Arcobacter species (becoming routinely isolated from a wide variety of food
      sources, especially of animal origin) to provide information for the
      identification within these species. Phospholipid differences were observed in
      the HPLC profiles. GC-MS analysis provided a complete fatty acid composition for
      each arcobacter that after pattern recognition analysis allows taxonomic
      classification of each species.

PMID- 17007439
TI  - The use of hydroxyl-radical-generating systems for the treatment of olive mill
      wastewaters.
AB  - Three hydroxyl-radical producing biomimetic systems, composed of CuII, hydrogen
      peroxide and pyridine, glucaric or succinic acid, were able to perform
      decolorization of olive mill wastewaters (OMW) >85 % within 3 d combined with a
      significant removal of total phenols (>75 %). The systems consisting of 50 mmol/L
      succinic acid, 5-10 mmol/L CuSO4 and 100 mmol/L H2O2 were the most effective at
      OMW treatment, and led to the reduction of phenol contents to <1 % along with
      high decolorization (>88 %) and acceptable values of chemical oxygen demand.

PMID- 17007440
TI  - The effect of light color on the nucleocytoplasmic and chloroplast cycle of the
      green chlorococcal alga Scenedesmus obliquus.
AB  - The color of light (white, red, blue, and green) had a significant effect on the
      growth and reproductive processes (both in the nucleocytoplasmic and chloroplast
      compartment of the cells) in synchronous cultures of Scenedesmus obliquus. This
      effect decreased in the order red > white > blue > green. In the same order, the
      light phase of the cell cycle (time when first autospores started to be released)
      was prolonged. The length of dark phase (time when 100 % of daughters were
      allowed to release from mothers) was not influenced and was the same for all
      colors. Critical cell size for cell division in green light was shifted to a
      smaller size (compared with cells grown in other lights) and so was the size of
      released daughters. The nuclear cycle was slowed in blue and even in green light,
      contrary to cells grown in red and white light. At the beginning of the cell
      cycle, one-nucleus daughters possess approximately 10 nucleoids; during the cell
      cycle their number doubled in all variants before the division of nuclei. Both
      events were delayed in cultures grown more slowly most markedly in green light.
      Smaller daughters in the green variant possessed a lower number of nucleoids.
      Motile cells released in continuous green or blue lights but not in red one were
      rarely observed.

PMID- 17007441
TI  - Comparative study of zooid and non-zooid forming strains of Scenedesmus obliquus.
      Physiology and cytomorphology.
AB  - Two zooid forming strains and four non-zooid strains of the green chlorococcal
      alga Scenedesmus obliquus were compared in terms of growth, morphological and
      physiological characteristics. Large differences were observed among the strains
      grown under various growth conditions (light and temperature). The assumption
      that the zooid forming strains may be similar was not confirmed. Since they
      considerably differed in daughter cells morphology, photosynthesis, growth rate
      in batch culture or commitment to cellular division. Molecular-genetic comparison
      of 18S RNA/DNA might distinguish zooid forming strains from non-zooid ones.

PMID- 17007443
TI  - Cyclooxygenase-2 (cox-2) expression and angiogenesis in intracranial ependymomas.
AB  - AIM: Cyclooxygenase-2 (Cox-2), the inducible key enzyme in the biosynthesis of
      prostaglandins, appears to play a role in the regulation of progression,
      invasiveness and angiogenesis of various neoplasms including some glial tumors.
      Little is known about the role of Cox-2 in angiogenesis and proliferation of
      ependymomas. We studied Cox-2 expression, Ki-67 labeling index (Ki-67 LI) and
      microvessel density (MVD) in 30 intracranial ependymomas and analyzed the
      relationship among these parameters to evaluate their importance in the tumor
      biology of ependymomas. RESULTS: The mean Ki-67 LI for all tumors ranged from 1 -
      50% (mean 9%). Statistically significant difference was present for Ki-67 LI
      between ependymomas (grade II, WHO) and anaplastic ependymomas (grade III, WHO)
      (p < 0.001) (mean Ki-67 LI for ependymoma, 2.8%, for anaplastic ependymomas,
      15.6%). Anaplastic ependymomas did not demonstrate a greater vascularization than
      ependymomas, and the MVD values were 84.5 +/- 39.7 for ependymomas, and 90.6 +/-
      61.4 for anaplastic ependymomas. Cox-2 immunohistochemical expression was
      observed in 19 tumors (63%). Although Cox-2 expression was slightly higher in
      anaplastic ependymomas, it was not statistically significant. No correlation was
      found between Cox-2 expression and MVD and Ki-67 LI. CONCLUSION: Similar to
      morphologic and prognostic heterogeneity in ependymomas, Cox-2 expression, MVD
      and Ki-67 LI also show a great variability. Other factors may be more important
      for the proliferation and angiogenesis of ependymomas.

PMID- 17007442
TI  - Laminar degeneration of the frontal and temporal cortex in neuronal intermediate
      filament inclusion disease (NIFID): a study original using alpha-internexin
      immunohistochemistry.
AB  - OBJECTIVE: To determine the laminar distribution of the pathological changes in
      the frontal and temporal lobe in neuronal intermediate filament inclusion disease
      (NIFID). METHOD: The distribution of the alpha-internexin-positive neuronal
      cytoplasmic inclusions (NCI), surviving neurons, swollen achromatic neurons (SN)
      and glial cell nuclei was studied across the cortex in gyri of the frontal and
      temporal lobe in 10 cases of NIFID. RESULTS: The distribution of the NCI was
      highly variable within different gyri, a peak in the upper cortex, a bimodal
      distribution with peaks of density in the upper and lower laminae, or no
      significant variation in density across the cortex. The surviving neurons were
      either bimodally distributed or exhibited no significant change in density across
      the cortex. The SN and glial cell nuclei were most abundant in the lower cortical
      laminae. In half of the gyri, variations in density of the NCI across the cortex
      were positively correlated with the SN. In some gyri, the surviving neurons were
      positively correlated with the SN and negatively correlated with the glial cell
      nuclei. In addition, the SN and glial cell nuclei were positively correlated in
      over half the gyri studied. CONCLUSION: The data suggest that frontal and
      temporal lobe degeneration in NIFID characterized by NCI, SN, neuronal loss and
      gliosis extends across the cortical laminae with considerable variation between
      cases and gyri. alpha-internexin-positive neurons in the upper laminae appear to
      be particularly vulnerable. The gliosis appears to be largely correlated with the
      appearance of SN and with neuronal loss and not related to the NCI.

PMID- 17007444
TI  - Suprasellar and intrasellar paragangliomas.
AB  - Neoplasms of the sellar region are entities with a large differential diagnosis.
      Although paraganglionic cells have not been demonstrated in the pituitary or
      adjacent structures, the existence of sellar region paragangliomas is well
      documented. To elucidate, in this area the nature of these unusual tumors is
      relatively difficult. Clinical history, physical examination, radiographic
      investigation as well as intraoperative gross observation are the same as those
      of sellar meningioma or pituitary adenoma. Immunohistochemistry, using
      neuroendocrine markers and electron microscopy are the two definitive diagnostic
      methods to differentiate among these entities. The clinical management, the
      possible pathogenesis of the tumor, the importance of immunohistochemistry in
      making the diagnosis and the clinical outcome of these patients are discussed.

PMID- 17007445
TI  - Morphophenotype of medulloblastoma in children and adults. The size of nuclei.
AB  - OBJECTIVE: Uniform cells with round, regular nuclei characterize the typical
      histologic aspect of medulloblastoma. Enlargement of nuclei distinguishes the
      large-cell medulloblastoma variant and is associated with a poor prognosis in
      pediatric medulloblastomas. The aim of the present study was to compare the size
      of nuclei between pediatric and adult medulloblastomas by a morphometric
      analysis. MATERIAL AND METHODS: In 79 neurosurgical specimens of cerebellar
      medulloblastomas, the maximum nuclear diameter of the largest nuclei was
      measured. Measurements were performed with a digital-image analysis system. The
      measure of the maximum diameter was chosen in order to reduce the split cell
      error. RESULTS: The difference between the mean values in children and adults was
      statistically significant (p = 0,001). The distribution of maximum values
      measured in each case had two distinct peaks in the two age groups, in 3.5% of
      adult cases and in more than 30% of pediatric cases the maximum nuclear size was
      superior to 12 microm. CONCLUSIONS: The present results show that nuclei of tumor
      cells in pediatric medulloblastomas are larger than those in adult
      medulloblastomas and confirm that the phenotype of medulloblastoma is different
      in the two age groups. Distinct genetic events can, thus, underlie
      medulloblastoma in childhood and adult age, the prognostic role of genetic
      variables can differ by age.

PMID- 17007446
TI  - Rare primary CNS anaplastic large cell lymphoma in an immunocompetent adult: a
      clinical-pathologic case report and review case of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Isolated anaplastic large cell lymphoma (ALCL)
      presenting in the primary central nervous system is distinctly uncommon. The
      authors describe a case that clinically and radiographically simulated a primary
      glial neoplasm. CLINICAL PRESENTATION: A 39-year-old immunocompetent male
      presented with seizures and a rapidly enlarging right occipital/parietal lesion.
      Magnetic resonance images demonstrated a right occipitoparietal lesion, hypodense
      on T1WI, with patchy contrast enhancement with gadolinium and significant white
      matter edema pattern on T2WI along with mass effect and midline shift.
      INTERVENTION: The patient underwent a frameless stereotactic assisted needle
      biopsy. There appeared to be a clear demarcation between white matter and tumor
      with no obvious necrosis. Biopsy showed a proliferation of single cells and
      poorly cohesive groups of cells with large, pleomorphic nuclei, many containing
      prominent nucleoli, and a moderate amount of cytoplasm. Immunohistochemical
      staining revealed CD-30 and ALK-positivity typical of ALCL, a rare form of T-cell
      lymphoma. An extensive workup revealed neither systemic disease nor evidence of
      immunocompromise. CONCLUSION: Reported in less than 20 patients, primary ALCL in
      an immunocompetent patient is rarely found intracranially; however, its ability
      to mimic glial neoplasms as well as other pathologies underlines its importance.

PMID- 17007447
TI  - Extensive mixed vascular malformation clinically imitating multiple sclerosis-
      case report.
AB  - Vascular malformations usually develop as a result of influence of teratogenic
      factor(s) acting in the defined embryonic/fetal period. However, in the case
      examined by us, various types of vascular malformations formed in different
      periods of the ontogenic development were found. They were seen in all parts of
      the central nervous system and clinically mimicked multiple sclerosis. On the
      background of generalized ischemic lesions of the CNS, certain kinds of vascular
      malformations were seen: cavernous or fetallike vessels within meninges,
      superficially located capillary angioma penetrating into the brain and spinal
      cord white matter, and arterio-venous pathological conglomerates forming
      meningeal angiomatosis. In pathological vessels, immunocytochemical assessment of
      vascular endothelium with antibodies against antigens CD31, CD34, von Willebrand
      factor and lectin Ulex europaeus was normal but examination of the vascular basal
      membrane compounds revealed poor immunoreactivity to laminin and fibronectin.
      There were no disturbances in expression of angiopoietin, platelet-derived growth
      factor, transforming growth factor beta and vascular endothelial growth factor
      receptors Tie-1/2, PDGFR-alpha/beta, endoglin and Flk-1, respectively. The
      presence of various types of pathological vessels originating from different
      ontogenic periods indicates remittent or prolonged influence of teratogenic
      factor(s) in all periods of fetal vessel development.

PMID- 17007448
TI  - Highlights in the history of neurosciences in Austria--review.

PMID- 17007449
TI  - [The children from Zanzibar, hepcidin and iron].

PMID- 17007450
TI  - [Management of patients after liver transplantation].
AB  - The success of liver transplantation essentially depends on the prevention and
      treatment of long term complications, which may be due to surgery, opportunistic
      infections, organ rejection and relapse of the initial liver disease. The side
      effects of immunosuppressive drugs--arterial hypertension, glucose intolerance
      and diabetes, dyslipidemia and obesity, renal failure, osteoporosis, malignancy,
      and anaemia--should be regularly screened and treated without delay. Surgical
      procedures in transplanted patients are safe and rarely followed by
      complications. Although pregnancy in this setting is considered at risk, because
      of prematurity and low birth weight, overall outcomes are favourable. The yearly
      influenza vaccination is strongly recommended. The survival and the quality of
      life of liver transplant patients also depend on a good communication between the
      general practitioner and the transplantation centre.

PMID- 17007451
TI  - [Cholestasis in adults. 1. Diagnostic procedure approach].
AB  - Cholestasis results abnormal biliary excretion, from the hepatocyte to the
      ampulla of Vater. Diagnosis of the cause of cholestasis is guided by liver
      ultrasonography, which can be done at the bedside. Management is then dictated by
      the level of obstruction. In intrahepatic cholestasis (without bile duct
      dilatation at ultrasonography), the workup will include blood tests for liver
      disease and liver biopsy will be discussed case by case. In extrahepatic
      cholestasis (with bile duct dilatation at ultrasonography), a multidisciplinary
      approach will involve the radiologist, the surgeon, as well as the endoscopist,
      and delineate the role of magnetic resonance cholangiopancreatography (MRCP),
      endoscopic ultrasonography (EUS) and endoscopic retrograde
      cholangiopancreatography (ERCP).

PMID- 17007452
TI  - [Cholestasis in adults. 2. Clinical signs and symptomatic treatment].
AB  - Cholestasis, a frequent occurrence in clinical practice, can be suspected when
      confronted to clinical signs (pruritus and jaundice) and/or increased blood level
      of alkaline phosphatases, gammaglutamyl transpeptidase and/or conjugated
      bilirubin. This short review will deal with the management of clinical
      manifestations and extrahepatic complications, whatever the cause of cholestasis.
      The management according to etiology will be dealt with in a separated chapter.

PMID- 17007453
TI  - [Clinical management of a patient with alcoholic cirrhosis].
AB  - Prolonged abstinence from alcohol is crucial in the management and prognosis of a
      patient with alcoholic cirrhosis. It is also important to prevent complications
      such as variceal bleeding, hepatocellular and extrahepatic cancers, and
      malnutrition. Liver transplantation should be considered in patients with
      persistent liver failure in spite of complete cessation of alcohol consumption.
      We provide some recommendations in commonly encountered clinical situations for
      compensated and decompensated alcoholic cirrhosis.

PMID- 17007454
TI  - [Therapy of chronic hepatitis B].
AB  - The aim of chronic hepatitis B therapy is to suppress hepatitis B virus
      replication, to control disease activity and progression towards cirrhosis. The
      first-line drug is the pegylated interferon a, which suppresses HBV replication
      in 40% of cases, albeit burdened with several contraindications and side effects.
      Lamivudine, a nucleoside analog inhibiting HBV reverse transcriptase, is
      indicated in case of failure or contraindication to interferon, may however lead
      to the selection of resistant mutant HBV strains (20% yearly). In that case,
      adefovir is indicated and has a lower risk of selection of resistant strains (5%
      yearly). More effective drugs (telbivudine and entecavir) will soon be available
      in Switzerland. Two inhibitors of HIV (tenofovir and emtricitabine) may also be
      used to treat hepatitis B in selected cases. Drug combinations, although
      supported by theoretical considerations, bring no known clinical benefit and are
      not reimbursed.

PMID- 17007455
TI  - [Functional bowel disorders: impact and limitations of evidence-based medicine].
AB  - Although tremendous efforts have been carried out to explore the physiopathology,
      classification and therapeutic modalities of functional bowels disorders, these
      conditions still elude the classical anatomical-clinical approach. This article
      summarizes recent advances in the field, discusses critically their impact on
      daily clinical practice and provides some practical recommendations.

PMID- 17007456
TI  - [Cervicobrachialgia: which management? (1) Point of view of the rheumatologist].

PMID- 17007457
TI  - [Leukotriene-modifiers in asthma treatment].
AB  - This review aims to evaluate the efficacy of the leukotriene modifiers in the
      different stages and subgroups of asthma. In mild asthma, they bring some
      improvement as monotherapy, but less than inhaled steroids. In moderate asthma,
      leukotriene modifiers associated with inhaled steroids seem to offer a slight
      advantage over placebo. No evidence of additional effect has been published in
      severe asthma. Exercice- and aspirin-induced asthma are particulary responsive to
      leukotriene modifiers. This treatment may also play a role in acute asthma. In
      practice, it is possible to select patients who benefit from those molecules. If
      only these "responders" are treated, leukotriene modifiers are an adequate
      treatment, easy to use and well tolerated.

PMID- 17007458
TI  - [The possible drawbacks of applying the DRG classification].
AB  - The objective of this article is to present the difficulties linked to the
      measure and use of the Diagnosis Related Group (DRG) as part of a hospital's
      production and management accounting evaluation system. We will present here all
      the criticisms brought forth in management literature against DRG
      classifications. The article isn't intended to argue against and to push people
      to reconsider the tool but rather to attract the attention of politicians and
      hospital managers to all the possible difficulties and outcomes that could be
      generated by the DRG, this in terms of either the AP-DRG or the German-DRG, the
      latter being the classification that has been adopted in Switzerland as the basis
      for the construction of the future Swiss-DRG.

PMID- 17007459
TI  - [The year 2006, between cloning and doping (2)].

PMID- 17007460
TI  - [On the Vatican and Dr. Robert Lanza].

PMID- 17007461
TI  - [A new portal to the human genome has just opened].

PMID- 17007462
TI  - [Vibrations in the health system].

PMID- 17007463
TI  - Schistosomiasis and the molecular biology of the male-female interaction of S.
      mansoni.
AB  - Parasitic helminths of the genus Schistosoma are the causative agents of
      schistosomiasis, an infectious disease affecting humans and animals. For humans,
      it is one of the most prevalent parasitemias in the world, second behind malaria.
      Estimates of the World Health Organisation (WHO) indicate that more than 200
      million people live in endemic areas (WHO, Fact Sheet No 115). With respect to
      animals, a number of 530 million cattle is estimated to live in endemic
      territories of Africa and Asia. In the last two decades ambitious efforts have
      been made to develop an effective vaccine against schistosomes, but without
      resounding success. In addition, there is a pressing need to develop new
      anthelmintics due to the potential emerging resistance against the commonly used
      drug praziquantel. Therefore, the understanding of essential physiological or
      developmental processes of schistosome biology and attempts to intervene in these
      processes may open new ways to control the parasite. Towards this end, one
      possibility is to study the unusual biology of schistosomes. These digenean
      parasites differ from other parasitic flukes by living in the blood vessels.
      Furthermore, schistosomatids are the only bisexual family of the class trematoda.
      A nearly unique phenomenon in nature is that a continuous pairing-contact is
      essential for the development of the reproductive organs of the female, an aspect
      for the possible design of novel control strategies.

PMID- 17007464
TI  - [Performance-related health disorders in farm animals--the ethical dimension].
AB  - The term "performance-related health disorders" has been defined by Bergmann
      (1992) as catabolic phenomena and pathological processes that are related to or
      caused by high productivity levels. In the past few years, a cause and effect
      relationship has been determined between numerous health disorders found in farm
      animals and their increased productivity. In contrast to the classic hereditary
      diseases, the performance-related health disorders are anthropogenic diseases.
      The severity of these disorders is, as a rule, determined by anthropogenic
      environmental factors. Breeding and keeping animals in such a way that they
      suffer from performance-related health disorders therefore is an ethical problem.
      Furthermore, it has also been a legal problem since the implementation of Section
      11b of the German Protection of Animals Act (TierSchG) in 1986. However, this ban
      has not been enforced; the federal ministry responsible argues that this is
      because there is still a "very controversial discussion" on the question of when
      the "line that separates breeding from 'problem' or 'agony breeding' (Qualzucht)"
      has been reached or overstepped. The following article takes a close look at the
      almost 20-year-old debate on the lack of enforcement. There is a large amount of
      circumstantial evidence that indicates that the problems that arise in
      determining whether specific animals fall under Section 11b TierSchG do not arise
      from a veterinary dispute but rather from the difficulty of identifying
      responsibilities. The traditional ethical model used to appeal to the feelings of
      responsibility in a layperson is the so-called Golden Rule ("do unto others as
      you would have them do unto you") which so far has not been applied to the area
      of animal breeding. The following article presents a model on how to create an
      awareness for ethical malpractice. The model makes it possible to use the change
      of perspective demanded by the Golden Rule and apply it to the area of animal
      breeding. This provides what could potentially be a useful aid in understanding
      ones own responsibility. While looking at possible solutions, two aspects are
      differentiated: the chronic non-enforcement of Section 11b TierSchG and the
      complete abolition of the problem. Possible solutions are presented for both
      areas and put up for discussion.

PMID- 17007465
TI  - Variation in the mortality rate of turkeys during transport to the slaughterhouse
      with travel distance and month.
AB  - Failure to comply with animal welfare requirements during the transport of
      turkeys to the slaughterhouse increases stress in animals, which is manifested by
      increased mortality rate during transport. The numbers of turkeys that died
      during transport or soon after arrival may serve as an important parameter to
      indicate the level of animal welfare during transport of turkeys. The number of
      turkeys that died during transport to slaughterhouses in the Czech Republic in
      the period from 1997 to 2004 was investigated. The mortality rate found was 0.28%
      +/- 0.06% but varied with travel distance. The lowest mortality rate was found in
      case of travel distance below 50 km (0.18% +/- 0.08%) while long travel distances
      resulted in considerable increase in the mortality rates of turkeys (between
      0.28% +/- 0.07 and 0.37% +/- 0.10%). The mortality rate of transported turkeys
      was also affected by the particular month of the year. Thus, the highest overall
      mortality rate occurred at long travel distances during winter months, i.e. in
      December (0.34% +/- 0.18%), January (0.32% +/- 0.06%), and February (0.36% +/-
      0.07%). The comparison of individual years has shown a long-term trend towards a
      decrease in turkeys' mortality during transportation to slaughterhouses from
      0.32% in 1998 to 0.20% in 2004. The decrease was statistically significant
      (Spearman's rank correlation coefficient r = -0.86, p < 0.01). This trend can be
      evaluated as positive.

PMID- 17007466
TI  - [The bacteriological and serological prevalence of Campylobacter spp. and
      Yersinia enterocolitica in fattening pig herds in Lower Saxony].
AB  - This article presents the results of a study on the occurrence of two bacteria
      that cause zoonoses, Campylobacter spp. and Yersinia enterocolitica. The study
      was carried out in 30 fattening herds in Lower Saxony, Germany, in 2004 and
      compares the results of bacteriological and serological methods of detection.
      Bacteriological findings of Campylobacter spp. in the faeces indicated that 69.7%
      of the fattening pigs were positive, but 81.2% tested positive serologically. All
      herds tested here were both bacteriologically and serologically positive for
      Campylobacter spp. Furthermore, only 8.4% tested positive for Yersinia
      enterocolitica in the faecal samples, but 66.8% of the animals were serologically
      positive for that bacterium. While bacteriological examination did not detect
      Yersinia enterocolitica in 56.7% of the herds tested, serological testing showed
      that only 16.7% of the units were without reacting animals. The great difference
      between the results of bacteriological and serological testing, especially in the
      case of Yersinia enterocolitica, can be explained by the intermittent intestinal
      excretion and predominance of this bacterium in the animals' tonsils. Low faecal
      excretion is also the reason for the low detection rate of 3.4% of Yersinia
      enterocolitica in the environmental samples, while that of Campylobacter spp. was
      33.3%. These results indicate that the environment plays only a secondary role in
      the distribution of Yersinia enterocolitica in pig herds.

PMID- 17007467
TI  - [Day-to day variability of cardiac pressure values in horses measured with right
      heart catheterization on 3 consecutive days].
AB  - In the present study, a right heart catheterisation was carried out on three
      consecutive days in 17 healthy horses to evaluate the day-to-day variability of
      cardiac pressure values. Cardiac pressure values were measured in the right
      atrium, the right ventricle, the pulmonary artery, and the pulmonary capillaries
      (pulmonary artery wedge pressure). Additionally it was examined wether the
      cardiac pressure variability was influenced by the heart rate and if there are
      differences between trained and untrained horses. Beside the coefficient of
      variances, statistical analysis with assessment of variance components were
      carried out. Therefore the variation between repeated measurements at one day and
      within one horse, and the variation between repeated measurements over three days
      and within the horses (day to day intraindividual variation) as well as the
      variation between the horses (interindividual variation) were taken into account.
      The absolute interindividual variance of the pressure values and the heart rate
      was between 0.4 and 19.6 at all day and for all horses. Between trained and
      untrained horses the variation of the pressure values and the heart rate was
      lower than in the trained horses. A significant difference between trained and
      untrained horses was seen in right atrial mean pressure (p < 0.001) and right
      atrial diastolic pressure (p < 0.005). The coefficient of variances of the mean
      heart rate was 11.8%. The coefficient of variances of the different pressure
      values ranged between 13.1 (mean pulmonary artery pressure) and 46.4% (right
      ventricular pressure). By splitting the variances, 54.4-78.9% of the variation
      was caused by the effect of days, 6.2-30.7% of the variation was caused by the
      effect of horses and 12.5-23% of the variation was caused by the repeated
      measurements at the different days. In sumary the results shows that nearly all
      of the pressure values had a low effect of days on the variation, thus cardiac
      pressure measurements at one day seem to be sufficient.

PMID- 17007468
TI  - [Disease monitoring in European mouflon (Ovis gmelini musimon) populations by
      clinical blood tests--aspects of epidemiology and treatment control of claw
      diseases].
AB  - European mouflon are in the focus of research since they were brought from the
      Tyrrhenic islands to the European mainland a hundred years ago. From the
      beginning many populations on European mainland suffer from different claw
      diseases which are unknown in their original habitats. Foot rot, the ovine
      purulent laminitis, whose existence im wild ruminants was negotiated some years
      before, furthermore claw alterations caused by primary or secondary lack of trace
      elements similar to the copper deficiency syndrome of the boreal deer species
      moose and reindeer and finally horn hyperplasia with a genetic background are
      found as main claw diseases in Central Europe. Object of this study was the
      acquiring of clinical parameters from blood for the installation of a mouflon
      specific diagnostic profile "claw diseases". Count of leucocytes (WBC), activity
      of Alkaline phosphatase, serum contents of phosphorus, iron, copper and zinc were
      found to be parameters for successful differential diagnosis and control of
      progress in cure programs.

PMID- 17007469
TI  - [First-time endoscopic detection of larvae of Gasterophilus spp. in the oral
      cavity in 14 warmblood horses].
AB  - Intraoral endoscopy is used as a standard diagnostic technique at the reporting
      clinics in horses presented with stomatological problems. Endoscopy of the oral
      cavity was performed using a chip camera, camera control unit, xenon cold light
      source and a rigid endoscope. In a three year period (2002 to 2004), second
      instars of Gasterophilus spp. were diagnosed in 14 warmblood horses 2 to 17 years
      of age. All horses were presented with masticatory problems or problems accepting
      the bit. In one horse oesophageal obstruction occurred in the course of larval
      migration. Oral endoscopy can not only be used for the diagnosis of dental
      disease but also for detection of instars of Gasterophilus spp. in the
      interdental spaces of maxillary cheek teeth.

PMID- 17007470
TI  - [Pilot study to evaluate the efficiency of insecticide-treated mosquito net
      fences for the protection of horses against nuisance insects in northern
      Brandenburg].
AB  - A fence of black mosquito netting of 100 cm height, pre-treated with 80 mg/m2 of
      deltamethrin and UV-protected, was used to shelter horses from nuisance and
      biting insects on pasture in northern Brandenburg. The netting material was
      attached to the surrounding poles of the existing fences at a height of 15 cm
      above ground. Three trial groups were selected grazing in spatially separated
      areas with comparable densities of insect populations. One paddock was completely
      fenced apart from a wall of 170 cm height and 70 m length. The second pasture had
      only partial protection with 126 m (13.4%) of fence out of a total perimeter of
      942 m. The third pasture served as control. Trap catches outside the fully or
      partially protected pasture were by at least 60% lower than those recorded for
      the control pasture. Digital pictures from five different anatomical regions
      indicated fewer flies on horses kept at the completely or partially protected
      areas as compared to the control area. The average attack rate in the protected
      areas amounted to 4.4 and 7.6 flies per horse at the completely or partially
      protected areas, respectively, as opposed to horses on the control pasture with
      172.1 flies. In comparison to the control pasture the horses grazing on the
      protected areas showed fewer defensive movements, grazing in an undisturbed
      manner.

PMID- 17007471
TI  - [Use of biochemical markers of bone metabolism in veterinary medicine].
AB  - Effective, non-invasive bone assessment methods for screening, diagnosis and
      follow-up of the skeleton are more and more requested in veterinary medicine. In
      contrast to clinical parameters, invasive methods and imaging techniques, indices
      of bone turnover is a tool for bone metabolism evaluation of the whole skeleton.
      Biochemical bone markers therefore provide a more real-time assessment of the
      bone status with simple blood- or urine-analysis. This article surveys currently
      available biochemical marker of bone metabolism used in veterinary medicine.
      Additionally, information is provided about physiological and pathological, as
      well as therapeutic variations of biochemical bone marker concentrations in
      various species.

PMID- 17007472
TI  - [Experiences with the FAMACHA-Eye-Colour-Chart for identifying sheep and goats
      for targeted anthelmintic treatment].
AB  - The bloodsuckling abomasal parasite Haemonchus contortus is the most pathogenic
      worm in sheep and goats. High prevalences of anthelmintic-resistant isolates make
      H. contortus difficult to control. Detecting the most anaemic animals could
      support a targeted selective treatment approach. Leaving the rest of the flock
      untreated would generate a refuge for anthelmintic-sensitive parasites. South
      African researchers tried the FAMACHA-Eye-Colour-Chart for anaemic sheep and
      goats with good success. Field studies, carried out in Northern Germany on
      naturally infected sheep and goats showed, that at a comparatively low prevalence
      of H. contortus the FAMACHA-test proved not being sufficient in detecting all
      animals with high fecal egg counts. Under these conditions there was no
      satisfying reliability to identify small ruminants for selective deworming only
      based on the FAMACHAEye-Colour-Test. But if not working hours are the limiting
      factor, the repeated score could support the selection of pale animals in need to
      be treated.

PMID- 17007473
TI  - [Integral psychiatry].

PMID- 17007474
TI  - [Short- and long-term results of a systematic benzodiazepine discontinuation
      programme for psychiatric patients].
AB  - BACKGROUND: Although guidelines for the use of benzodiazepines emphasise that
      these drugs should only be prescribedfor short periods of time, in practice long
      term usage persists and can be a serious problem. There is afear among patients
      and among doctors prescribing the drugs that symptoms will become more acute if
      attempts are made to terminate the regimen. AIM: To determine the short- and long
      term results of a standardized method for discontinuing the use of
      benzodiazepines (BZD) and to test whether these results were related to the age
      and gender of the patients, the BZD dosage level and the treatment modality.
      METHOD: A retrospective cohort study was performed at the Department of
      Psychiatry of the Radboud University Nijmegen Medical Centre. A systematic BZD
      discontinuation programme was offered by the Department of Psychiatry to patients
      who had been using BZD for at least three months. By studying the medical
      records, by conducting telephone interviews and by examining the prescription
      data of the GP or the pharmacy it was ascertained how many patients managed to
      become abstinent in the short- and long-term. RESULTS: Upon termination of the
      discontinuation programme 65% of the patients had managed to stop taking BZD and
      at follow-up approximately 2 years later 37% of the patients interviewed had not
      used BZD for the last 3 months. Neither age, nor gender, nor treatment modality
      predicted BZD usage immediately after the end of the discontinuation programme or
      at the 2-year follow-up. A high dose of BZD was the only significant predictor of
      post-programme usage 2 years later. CONCLUSION: A systematic discontinuation
      programme seems to be just as effective for psychiatric patients as it isfor
      general practice patients and deserves to be included in the regular treatment
      programmes provided by psychiatric practices.

PMID- 17007475
TI  - [Predicting the success of a benzodiazepine discontinuation programme: myths or
      clinical wisdom?].
AB  - BACKGROUND: After successful completion of a benzodiazepine withdrawal programme
      it nevertheless is hard to remain abstinent in the long term. AIM: To determine
      to what extent the success of a benzodiazepine discontinuation programme for
      psychiatric patients with chronic benzodiazepine use (> or = 3 months) can be
      predicted from the severity of the anxiety, sleep disorders and depressive
      symptoms, and from the level of benzodiazepine dependence. The predictive values
      of coping style and personality characteristics were also studied. METHOD: A
      prognostic cohort study with patients of the Radboud University Nijmegen Medical
      Centre was conducted. Before entering the programme 92 patients were given a
      psychological assessment. Anxiety level, benzodiazepine dependence, coping style
      and personality traits were measured by means of psychological questionnaires.
      The DSM-IV axis I classification for each patient was known. Patients who had
      stopped their medication immediately after the discontinuation programme ended (n
      = 6o) were compared with patients who had not been successful in completing the
      programme (n = 32). Thereafter, patients who were still abstinent at the follow
      up about 2 years later (n = 25) were compared with patients who at that time
      /used benzodiazepine (n = 43). RESULTS: Of all the variables examined, it was
      only a specific coping style whereby patients expressed their (negative) emotions
      which was associated with the short- and long-term success of the discontinuation
      programme. The more patients expressed their negative emotions, the greater the
      chance of a successful outcome and permanent abstinence. Coping style, however,
      predicted for only a small proportion of the variance in the success of the
      discontinuation programme. CONCLUSION: The psychological characteristics and the
      DSM-IV axis I classifications should not exert undue influence on the clinician's
      decision to advise the patient to stop or continue taking benzodiazepines.

PMID- 17007476
TI  - [Diagnosing frontotemporal dementia, a chameleon in psychiatry].
AB  - BACKGROUND: Frontotemporal dementia (FTD) generally has a presenile onset,
      behavioural problems dominate the clinical picture and cognitive functions are
      still relatively intact. Therefore particularly in the early stages of FTD it is
      difficult to differentiate this type of dementia from other types of dementia and
      psychiatric disorders. AIM: To review the options currently available for
      diagnosing FTD and to evaluate their significance for clinical practice. METHOD:
      A literature search via PubMed, Embase and the Cochrane Library (1999-2005) using
      the key words 'frontotemporal dementia' and 'diagnosis' or 'differential
      diagnosis'. Genetic and post-mortem studies were excluded. RESULTS: The selected
      literature concerned differential clinical symptoms, neuropsychological research
      and questionnaires, neuroimaging and fluid abnormalities and dealt mainly with
      the difference between FTD and other types of dementia but not with differences
      between FTD and psychiatric disorders. CONCLUSION: Measuring instruments that are
      helpful for diagnosing FTD are the Manchester Behavioural Questionnaire, the
      Frontal Behaviour Inventory and the Frontal Assessment Battery. Even better
      indicators of FTD are asymmetrical frontotemporal structural abnormalities in a
      CT- or MRI-scan and a decrease infrontal metabolism and perfusion in a PET- or
      SPECT-scan, although not all detected abnormalities are specific for FTD.
      Whatever the method used, early diagnosis is difficult; the sensitivity of nearly
      all diagnostic methods increases as the illness progresses. On the basis of this
      review of the literature some diagnostic techniques are recommended that can be
      applied if FTD is suspected.

PMID- 17007477
TI  - [Late-onset schizophrenia: is it a dementia nonpraecox? Review article with
      advice on differential diagnosis].
AB  - BACKGROUND: For many years now researchers have been discussing whether late
      onset schizophrenia (LOS) is in fact a separate subgroup of schizophrenia. They
      also want to find out whether LOS has a neurodegenerative aetiology and is a
      progressive illness. AIM: To obtain insight into the clinical aspects,
      aetiological factors and the course of late-onset schizophrenia. In addition,
      advice is given about better ways of diagnosing LOS in clinical practice and
      about differentiating LOS from dementia. METHOD: The literature was searched via
      Medline and the Cochrane Library on the basis of the key words '(very) late-onset
      schizophrenia' and 'paraphrenia' combined with 'course', 'outcome', 'cognition',
      'decline', 'white matter hyperintensities', 'MRI', and 'neuropsychological',
      'postmortem' and cerebrospinal fluid'. The period studied was from 1960 to
      November 2004. RESULTS: Clinical parameters andfunctional and structural brain
      research point to differences from and similarities to the early form of
      schizophrenia (EOS). In cases of 'very-late-onset schizophrenia-like psychosis'
      (VLOS) the clinical differences vis-a-vis EOS are even more marked. It is not
      known to what extent neurodegenerative factors play a role. There is no clear
      consensus about the course of (V)LOS either. CONCLUSION: In view of the
      aetiologial and physiopathological factors it is still not clear whether (V)LOS
      can be differentiated from EOS on a neurobiological basis. There is insufficient
      proof about the extent to which (V)LOS is a dementia nonpraecox with
      neurodegenerative aetiology. To achieve clear differentiation between the various
      forms of dementia it is essential that the clinical diagnosis of LOS is supported
      as strongly as possible and is evaluated continually.

PMID- 17007478
TI  - [Late-onset psychopathology: a difficult diagnostic puzzle].

PMID- 17007479
TI  - [Complementary and alternative medicine and psychiatry: opinions of patients and
      psychiatrists].
AB  - All over the world people are becoming increasingly interested in complementary
      and alternative medicine (CAM). Some would like CAM to be integrated into
      conventional medicine, others are strongly opposed to its integration. We
      distributed printed questionnaires in order to discover the views of patients and
      psychiatrists on CAM and to obtain information about the extent to which people
      actually use CAM. Patients often turn to CAM and are generally satisfied with the
      results and many support integration. Psychiatrists underestimate the number of
      times that patients use CAM. They are reluctant to support the integration of
      alternative medicine but are less opposed to the integration of complementary
      medicine. Patients and psychiatrists want more information about CAM. Asking the
      patients whether they use CAM seems desirable.

PMID- 17007480
TI  - [The development of psychotic symptoms in later life: late-onset schizophrenia or
      frontotemporal dementia? A case study].
AB  - The diagnosis of psychotic disorders that develop later in life is complicated,
      as can be seen from the case of a 65-year-old woman. Initially she was admitted
      to hospital for psychotic depression, but after some time doubts arose regarding
      the diagnosis. The most striking symptoms were bizarre delusions with acoustic,
      haptic and gustatory hallucinations. In addition, she showed behavioral and
      personality changes. It is difficult to establish whether a patient has late
      onset schizophrenia or frontotemporal dementia. The similarities and differences
      between the symptoms of these two disorders are discussed and advice is given to
      assist with clinicians with diagnosis in the future.

PMID- 17007481
TI  - [Anxiety disorders and epilepsy: not unknown, but sometimes unexpected. A case
      study].
AB  - Epileptic disorders can manifest themselves with symptoms of anxiety and panic.
      In clinical practice it is not always easy to achieve a correct diagnosis. The
      subject of this case study is an adult with symptoms of anxiety and panic who was
      referred to the mental health care service but who was diagnosed as having
      epilepsy when subjected to a supplementary examination. Psychological and in
      particular anxiety symptoms in epilepsy are discussed. The psychiatrist needs to
      consider the possibility of epilepsy in a patient presenting with anxiety
      symptoms.

PMID- 17007483
TI  - [Reaction to 'What is a delusion?'].

PMID- 17007482
TI  - [Reaction to 'The end of the mental healthcare sector'].

PMID- 17007484
TI  - Costs and benefits of combining probation and substance abuse treatment.
AB  - AIMS OF THE STUDY: We compared seamless combination of probation and treatment
      (where the probation officer is co-located with treatment provider or is actively
      engaged in treatment) to traditional probation where treatment is left to the
      client's choice. METHODS: Clients were randomly assigned to either seamless or
      traditional probation. We used a decision analytic approach which had two
      advantages: First it separated estimation of probability of adverse events (e.g.
      hospitalization) from the daily cost of the adverse event, thereby allowing use
      of estimates of daily costs available within the literature. Second, the reliance
      on daily probability of various adverse events also had the benefit of reflecting
      both length of the event and its intermittent re-occurrence. Subjects were 272
      clients on probation in Northern Virginia and Maryland in the United States.
      Clients were randomly assigned to seamless and traditional probation and were
      followed for an average of 2.75 years (arrest information was only available for
      1 year); 77% of clients participated in the follow-up interviews. At baseline,
      there was no statistically significant difference among the clients. RESULTS:
      During the follow-up period, clients in the seamless probation had less
      recidivism but the cost savings from this component (dollar 2.31 per client per
      follow-up day) was not sufficient to overcome increased costs due to mental
      hospitalization of seamless clients (dollar 13.50 per client per follow-up day),
      cost of delivery of seamless probation (dollar 2.58 per client per follow-up
      day), more frequent use of jail/prison for clients in the seamless group (dollar
      2.08 per client per follow-up day) and additional treatment costs (dollar 1.24
      per client per follow-up day). The expected cost of seamless probation and its
      consequences was dollar 38.84 per follow-up day. The expected cost of traditional
      probation and its consequences was dollar 21.60 per follow-up day. Seamless
      probation was dollar 6,293 more expensive than traditional probation per client
      per year. DISCUSSION: Sensitivity analysis suggested that the analysis was not
      sensitive to small change in any single cost or probability estimate. Sensitivity
      analysis suggested that increased supervision intensity and use of sanctions had
      contributed to lower cost-effectiveness. IMPLICATIONS: One possible way of
      improving seamless probation is to improve the intensity of the substance abuse
      treatment while reducing the intensity of supervision to its traditional levels.
      This analysis was limited to 2.75 years follow-up period and does not address
      cost savings that might occur after this period.

PMID- 17007485
TI  - Income and employment of people living with combined HIV/AIDS, chronic mental
      illness, and substance abuse disorders.
AB  - BACKGROUND: This paper examines the labor market outcomes of HIV triply-diagnosed
      adults having a combination of HIV, mental illness and substance abuse problems.
      AIMS OF THE STUDY: We sought to determine the sources of money income for HIV
      triply diagnosed adults (public or private), receipt of transfer income (e.g.,
      welfare) and financial support from others. We further sought to ascertain their
      employment status and analyze the characteristics associated with full- and part
      time employment. METHODS: We use self-reported money income during the past 30
      days and self-reported employment status. We calculate earnings losses due to
      illness by subtracting self-reported earnings from average earnings for all U.S.
      workers based on 5-year age and gender categories. We provide descriptive
      statistics to show how income and employment vary by patient characteristics and
      logistic regression analysis to examine correlates of income and employment.
      RESULTS: Average income is below the poverty level for single individuals, with
      more than two-thirds coming from public income sources. The likelihood of
      receiving disability/retirement income was lower among those with the worst
      mental health (RR=0.80; 95% CI=0.64, 0.97). Blacks were more likely than others
      to rely on public assistance (RR=1.24; 95% CI=1.02, 1.55) and married individuals
      were less likely (RR=0.60; 95% CI=0.41, 0.79). While most private income comes
      from employment, less than 15 percent of this population is employed full- or
      part-time. On a monthly basis, the average individual in our sample lost $2,726
      in income when compared to the earnings of individuals of the same age and sex in
      the general population. The relative probability of current full-time/part-time
      employment was lower among females (RR=0.56; 95% CI=0.34, 0.83); such employment
      also was lower among those in the worst physical health (RR=0.39; 95% CI=0.26,
      0.65) and those in moderate physical health (RR=0.55; 95% CI=0.34, 0.81) relative
      to those in the best physical health. IMPLICATIONS FOR HEALTH CARE PROVISION AND
      USE: This population represents an important opportunity for better health and
      labor market outcomes through prevention and improved treatment adherence.
      IMPLICATIONS FOR HEALTH POLICIES: Despite its relatively small size (at least
      100,000), this population merits closer attention due to a combination of their
      high medical and companion social costs (e.g., income transfers) and the large
      potential for improving their ability to earn income. IMPLICATIONS FOR FURTHER
      RESEARCH: Future research should determine the marginal contribution of mental
      health conditions or substance abuse on income or labor market outcomes relative
      to individuals having only HIV/AIDS. This would allow policymakers to better
      understand how much of income and employment can be attributed to HIV/AIDS,
      mental health or substance abuse. Future work also should examine the impact of
      integrated treatment services on income and employment for this population.

PMID- 17007486
TI  - Cost of depression in Europe.
AB  - BACKGROUND: Depression is one of the most disabling diseases, and causes a
      significant burden both to the individual and to society. WHO data suggests that
      depression causes 6% of the burden of all diseases in Europe in terms of
      disability adjusted life years (DALYs). Yet, the knowledge of the economic impact
      of depression has been relatively little researched in Europe. AIMS OF THE STUDY:
      The present study aims at estimating the total cost of depression in Europe based
      on published epidemiologic and economic evidence. METHODS: A model was developed
      to combine epidemiological and economic data on depression in Europe to estimate
      the cost. The model was populated with data collected from extensive literature
      reviews of the epidemiology and economic burden of depression in Europe. The cost
      data was calculated as annual cost per patient, and epidemiologic data was
      reported as 12-month prevalence estimates. National and international statistics
      for the model were retrieved from the OECD and Eurostat databases. The aggregated
      annual cost estimates were presented in Euro for 2004. RESULTS: In 28 countries
      with a population of 466 million, at least 21 million were affected by
      depression. The total annual cost of depression in Europe was estimated at Euro
      118 billion in 2004, which corresponds to a cost of Euro 253 per inhabitant.
      Direct costs alone totalled dollar 42 billion, comprised of outpatient care (Euro
      22 billion), drug cost (Euro 9 billion) and hospitalization (Euro 10 billion).
      Indirect costs due to morbidity and mortality were estimated at Euro 76 billion.
      This makes depression the most costly brain disorder in Europe, accounting for
      33% of the total cost. The cost of depression corresponds to 1% of the total
      economy of Europe (GDP). DISCUSSION: Our cost results are in good agreement with
      previous research findings. The cost estimates in the present study are based on
      model simulations for countries where no data was available. The predictability
      of our model is limited to the accuracy of the input data employed. As there is
      no earlier cost-of-illness study conducted on depression in Europe, it is,
      however, difficult to evaluate the validity of our results for individual
      countries and thus further research is needed. CONCLUSION: The cost of depression
      poses a significant economic burden to European society. The simulation model
      employed shows good predictability of the cost of depression in Europe and is a
      novel approach to estimate the cost-of-illness in Europe. IMPLICATIONS FOR HEALTH
      CARE PROVISION AND POLICIES: Health and social care policy and commissioning must
      be evidence-based. The empirical results from this study confirm previous
      findings, that depression is a major concern to the economic welfare in Europe
      which has consequences to both healthcare providers and policy makers. One
      important way to stop this explosion in cost is through increased research
      efforts in the field. Moreover, better detection, prevention, treatment and
      patient management are imperatives to reduce the burden of depression and its
      costs. Mental healthcare policies and better access to healthcare for mentally
      ill are other challenges to improve for Europe. IMPLICATIONS FOR FURTHER
      RESEARCH: This study has identified several research gaps which are of interest
      for future research. In order to better understand the impact of depression to
      European society long-term prospective epidemiology and cost-of-illness studies
      are needed. In particular data is lacking for Central European countries. On the
      basis of our findings, further economic evaluations of treatments for depression
      are necessary in order to ensure a cost-effective use of European healthcare
      budgets.

PMID- 17007487
TI  - Modeling costs and burden of informal caregiving for persons with bipolar
      disorder.
AB  - BACKGROUND: Informal caregiving contributes significantly to the health and well
      being of chronically ill persons. While a vast literature demonstrates this
      connection, the cost and financial burden of informal caregiving has received
      considerably less research attention, especially as it-pertains to bipolar
      disorder. AIMS OF THE STUDY: This paper develops an integrated burden model of
      informal caregiving, which is contrasted with other more traditional models of
      caregiving costs, and then uses these models to estimate the financial burden of
      bipolar disorder. The "goodness" of these various models is measured in terms of
      their correlation with measures of objective and subjective burden for caregivers
      of persons with bipolar disorder. METHODS: The study was an ancillary protocol to
      the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and
      included primary caregivers of 500 people with bipolar disorder. Approximately
      96% (n=486) caregivers participated in the study. Caregivers were interviewed at
      baseline, and six and 12 months after an initial interview. The semi-structured
      interview included questions on (i) subjective distress; (ii) the types of
      support and services; (iii) caregiver use of formal and informal services and
      support; and (iv) contributions received from the relative with bipolar over the
      past month. RESULTS: The correlations between financial burden and psychological
      burden measures were positive and statistically significant in cases where all
      resource costs were measured but adjusted for reciprocated giving and customary
      generosity (the integrated model). The strength of correlations was greater when
      time is valued at its opportunity cost (and not imputed) and the caregiving costs
      based on this valuation approach were logarithmically transformed. DISCUSSION:
      The magnitude of the correlations is consistent with the notion that caregiver
      burden is a coherent construct with multiple different dimensions. Financial
      burden appears to be a unique dimension that is significantly intercorrelated
      with psychological measures but is not redundant with them. The robustness of
      these findings need to be tested with larger samples and across caregiver illness
      groups. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Caregiving is likely to
      have health and stress-related consequences that increase caregiving costs.
      Understanding which costs are associated with feelings of burden can be used to
      inform the design of interventions to minimize the stressful or burdensome
      aspects of caregiving. Giving back reduces the magnitude of caregiving costs and
      the sense of psychological burden. Interventions that develop the potential to
      "give back" are likely to be beneficial for both the caregiver and the care
      receiver as it increases reciprocity and decreases dependency. IMPLICATIONS FOR
      FURTHER RESEARCH: Caution is needed in estimating the costs of informal
      caregiving needs as many costs are possible but their relationship to burden
      varies in strength and significance. Assumptions related to what is given and
      received and how this relates to expected patterns of giving and receiving in
      measuring and determining financial burden and costs are particularly important,
      as is the valuation of time.

PMID- 17007488
TI  - Consensus statement on negative pressure wound therapy (V.A.C. Therapy) for the
      management of diabetic foot wounds.
AB  - In 2004, a multidisciplinary expert panel convened at the Tucson Expert Consensus
      Conference (TECC) to determine appropriate use of negative pressure wound therapy
      as delivered by a Vacuum Assisted Closure device (V.A.C. THERAPY, KCI, San
      Antonio, Texas) in the treatment of diabetic foot wounds. These guidelines were
      updated by a second multidisciplinary expert panel at a consensus conference on
      the use of V.A.C. THERAPY, held in February 2006, in Miami, Florida. This updated
      version of the guidelines summarizes current clinical evidence, provides
      practical guidance, offers best practices to clinicians treating diabetic foot
      wounds, and helps direct future research. The Miami consensus panel discussed the
      following 12 key questions regarding V.A.C. THERAPY: (1) How long should V.A.C.
      THERAPY be used in the treatment of a diabetic foot wound? (2) Should V.A.C."
      THERAPY be applied without debriding the wound? (3) How should the patient using
      V.A.C. THERAPY be evaluated on an outpatient basis? (4) When should V.A.C.
      THERAPY be applied following revascularization? (5) When should V.A.C. THERAPY be
      applied after incision, drainage, and debridement of infection? (6) Should V.A.C.
      THERAPY be applied over an active soft tissue infection? (7) How should V.A.C.
      THERAPY be used in patients with osteomyelitis? (8) How should noncompliance to
      V.A.C. THERAPY be defined? (9) How should V.A.C. THERAPY be used in combination
      with other modalities? (10) Should small, superficial wounds be considered for
      V.A.C. THERAPY? (11) How should success in the use of V.A.C. THERAPY be defined?
      (12) How can one combine effective offloading and V.A.C. THERAPY?

PMID- 17007489
TI  - Monitoring dopamine in vivo by microdialysis sampling and on-line CE-laser
      induced fluorescence.
AB  - Microdialysis sampling was coupled on-line to micellar electrokinetic
      chromatography (MEKC) to monitor extracellular dopamine concentration in the
      brains of rats. Microdialysis probes were perfused at 0.3 microL/min and the
      dialysate mixed on-line with 6 mM naphthalene-2,3-dicarboxaldehye and 10 mM
      potassium cyanide pumped at 0.12 microL/min each into a reaction capillary. The
      reaction mixture was delivered into a flow-gated interface and separated at 90-s
      intervals. The MEKC separation buffer consisted of 30 mM phosphate, 6.5 mM SDS,
      and 2 mM HP-beta-CD at pH 7.4, and the electric field was 850 V/cm applied across
      a 14-cm separation distance. Analytes were detected by laser-induced fluorescence
      excited using the 413-nm line of a 14-mW diode-pumped laser. The detection limit
      for dopamine was 2 nM when sampling by dialysis. The basal dopamine concentration
      in dialysates collected from the striatum of anesthetized rats was 18 +/- 3 nM (n
      = 12). The identity of the putative dopamine peak was confirmed by showing that
      dopamine uptake inhibitors increased the peak and dopamine synthesis inhibitors
      eliminated the peak. The utility of this method for behavioral studies was
      demonstrated by correlating dopamine concentrations in vivo and with psychomotor
      behavior in freely moving rats following the intravenous administration of
      cocaine. Over 60 additional peaks were detected in the electropherograms,
      suggesting the potential for monitoring many other substances in vivo by this
      method.

PMID- 17007490
TI  - Measurement of gas-phase hydroperoxides by chemical ionization mass spectrometry.
AB  - A new method for the detection of gas-phase hydroperoxides is described. The
      clustering chemistry of CF3O- is exploited to produce speciated measurements of
      several hydroperoxides with high sensitivity and fast time response.
      Correspondence of airborne observations made with this technique and the
      established HPLC method is illustrated. CF3O- appears to be a highly versatile
      reagent ion for measurements of both weak and strong acids in the atmosphere.

PMID- 17007491
TI  - Charge neutralization process of mobile species at any distance from the
      electrode/solution interface. 1. Theory and simulation of concentration and
      concentration gradients developed during potentiostatic conditions.
AB  - The theoretical framework of a general model for the simulation of concentration
      profiles of electroactive and nonelectroactive species, driven by an
      electrochemical process under potentiostatic conditions, is presented. Based on
      this analysis, finite differences simulations are performed to calculate the
      actual profiles under different experimental conditions. Furthermore, the effect
      of experimental parameters (diffusion coefficients of the ions of the redox
      couple or the supporting electrolyte, charge of the different species, etc.) on
      the concentration profiles is also examined. The results obtained when low and
      high concentrations of supporting electrolyte are compared aid understanding of
      the effect of the electrolyte on the measurements. The presented model also
      underlines the role of supporting electrolyte species when nonspecific techniques
      are employed to measure the concentration changes produced by electroactive
      species. On the other hand, if a highly specific technique were used to detect
      changes in the concentration or concentration gradient of a given species, then
      it would be possible to estimate the respective profiles of the other species.
      The simulations suggest that techniques measuring concentration gradients are
      more sensitive to determining concentration changes than those involving a
      measurable linearly related to concentration.

PMID- 17007492
TI  - Charge neutralization process of mobile species at any distance from the
      electrode/solution interface. 2. Concentration gradients during potential pulse
      experiments.
AB  - The theoretical model presented in part 1 of this work is employed to simulate
      and fit experimental probe beam deflection (PBD) data of Fe(CN)6(3-)/Fe(CN)6(4-)
      and Fe3+/Fe2+ couples. Current and beam deviation dependency on time at constant
      potential (chronoamperometry and chronodeflectometry) is analyzed via a new
      treatment based on the migration and diffusion properties of all the species
      involved. The diffusion coefficients of electroactive species are obtained by
      fitting chronoamperometric curves. Those coefficients are then employed to
      simulate the respective chronodeflectometric profiles. The experimental data and
      the theoretical function are fitted by the minimum squares Simplex algorithm. The
      effect of working with systems in which both electroactive species are charged is
      discussed in detail. Specifically, the possibility of quantitative analysis of
      nonspecific techniques data is analyzed when a relative high concentration of
      supporting electrolyte is used. Such analysis widens the scope of techniques as
      PBD since in many cases the effect of supporting electrolyte species could be
      negligible as compared to the response of electroactive species. The variation of
      the refraction index with the concentration gradient of each soluble species is
      also discussed.

PMID- 17007493
TI  - Cyclic chronopotentiometry as a detection tool for flowing solution systems.
AB  - Cyclic chronopotentiometry provides a very simple detection method, which may be
      particularly useful in capillary electrophoresis (CE) and microseparation
      systems. It has been shown that for disk microelectrodes it is possible to define
      safe reduction and oxidation currents that would never lead to the formation of
      H2 or O2 gas bubbles, even if they are applied for an indefinitely long time
      period. During end-column CE detection, currents passing through the working
      microelectrode can be completely controlled by the external electronic circuit
      and they are not affected by the separation current. Consequently, problems
      created by the offset potential in CE can be completely eliminated. The detection
      can be accomplished through a variety of different mechanisms; however,
      generation of the electrode response as a result of analyte adsorption seems to
      be most common. The method is applicable to many analytes, which do not have to
      be electroactive. The analytical signal is obtained by monitoring the change in
      the average electrode potential (calculated for either a cathodic or an anodic
      half-cycle) caused by an analyte interacting with the electrode. The analytical
      signal is proportional to the analyte concentration, within a concentration range
      extending over approximately 2 orders of magnitude.

PMID- 17007494
TI  - In vitro continuous amperometry with a diamond microelectrode coupled with video
      microscopy for simultaneously monitoring endogenous norepinephrine and its effect
      on the contractile response of a rat mesenteric artery.
AB  - Continuous amperometry with a diamond microelectrode and video microscopy were
      used to record (in vitro) endogenous norepinephrine release simultaneously with
      the evoked contractile response of a mesenteric artery from a healthy Sprague
      Dawley rat. Norepinephrine (NE) is a vasoconstricting neurotransmitter released
      from sympathetic nerves that innervate the smooth muscle cell layers surrounding
      arteries and veins. Using these two techniques along with several drugs, the NE
      released at sympathetic neuroeffector junctions nearby the microelectrode was
      measured as an oxidation current. Key to the amperometric measurement was the use
      of a diamond microelectrode because of the response sensitivity, reproducibility,
      and stability it provided. NE release was elicited by electrical stimulation at
      frequencies between 1 and 60 Hz, with a maximum response seen at 20 Hz.
      Confirmation that the oxidation current was, in fact, associated with endogenous
      NE came from the results of several drugs. Tetrodotoxin (TTX, 0.3 microM), a
      voltage-dependent sodium channel antagonist that blocks nerve conduction,
      abolished both the oxidation current and the arterial constriction. The alpha(2)
      adrenergic autoreceptor antagonist, yohimbine (1.0 microM), caused an increase in
      the oxidation current and the corresponding constriction. The addition of cocaine
      (10 microM), an antagonist that inhibits neuronal NE reuptake, caused both the
      oxidation current and the contractile response to increase. These results,
      combined with the fact that the hydrodynamic voltammetric E(1/2) for endogenous
      NE was identical to that for a standard solution, confirmed that the oxidation
      current was due to NE and that this compound caused, at least in part, the
      contractile response. The results demonstrate that continuous amperometric
      monitoring of NE with a diamond microelectrode and video imaging of vascular tone
      allow real time local measurement of the temporal relationship between nerve
      stimulated NE release and arterial constriction.

PMID- 17007495
TI  - Ultrafast gas chromatographic separation of organophosphor and organosulfur
      compounds utilizing a microcountercurrent flame photometric detector.
AB  - A microcountercurrent flame photometric detector (microcc-FPD) was adapted and
      optimized for ultrafast gas chromatographic (GC) separation and detection of
      organophosphor (OP) and organosulfur (OS) compounds on short chromatographic
      columns. Air and hydrogen are introduced to the microcc-FPD from opposite
      directions, creating a hydrogen-rich flame. In this microcc-FPD, combustion takes
      place between the burner tips without touching them. The separation between the
      tips and the flame reduces heat loss from the flame to the surrounding
      environment, resulting in low hydrogen consumption and a compact flame. The
      microcc-FPD is capable of detecting very narrow (13 ms) chromatographic peaks. An
      ultrafast GC separation of a group of six OP and OS compounds is achieved within
      less than 5 s using fast temperature programming of a 0.5-m-long microbore
      column. Very fast separations are also demonstrated on a 1-m-long microfabricated
      column consisting of 150-microm-wide, 240-microm-deep channels, etched in a 1.9
      cm square silicon chip, covered with a Pyrex wafer, and statically coated with
      dimethyl polysiloxane. With a hydrogen flow rate of 10 mL/min, the detection
      limit for OP is 12 pg of P/s and 3 ng of S/s for OS compounds at a signal-to
      noise ratio of 2. The coupling of a microfabricated column and a miniature FPD is
      an important step toward the development of a miniaturized GC-FPD capable of
      ultrafast detection of low levels of OP and OS compounds.

PMID- 17007496
TI  - Simultaneous determination of carbohydrates, carboxylic acids, alcohols, and
      metals in foods by high-performance liquid chromatography inductively coupled
      plasma atomic emission spectrometry.
AB  - The applicability of the HPLC-ICP-AES coupling for the simultaneous determination
      of carbohydrates, carboxylic acids, alcohols, and metals in a single
      chromatographic run has been demonstrated in the present work. Five saccharides,
      glucose, fructose, sucrose, sorbitol, and lactose; five carboxylic acids, citric,
      tartaric, malic, lactic, and acetic; and three alcohols, glycerol, ethanol, and
      methanol, have been determined. A H+ cation exchange column has been used to
      separate these compounds. The chromatograms have been obtained by monitoring the
      carbon emission signal at 193.09 nm. The results obtained by HPLC-ICP-AES have
      been compared against those found with conventional detection systems (i.e.,
      refractive index, UV, and photodyode array detectors). The HPLC-ICP-AES method
      has shown the following features: (i) organic compounds and metals can be
      simultaneously determined; (ii) the detection method is universal; (iii) for
      nonvolatile organic compounds, a complete calibration line can be obtained from a
      single injection; and (iv) it provides absolute limits of detection similar to or
      lower than those found with conventional detection systems (i.e., on the order of
      several tens of nanograms of organic compound). The methodology has been
      validated through the analysis of food samples such as juices, isotonic
      beverages, wines, and a certified nonfat milk powder sample.

PMID- 17007497
TI  - Time-dependent phenomena in the potential response of ion-selective electrodes
      treated by the Nernst-Planck-Poisson model. 1. Intramembrane processes and
      selectivity.
AB  - The variability of selectivity coefficients, resulting from potential changes
      over time and the concentration ratio of primary to interfering ions, impedes
      many practical applications of ion-selective electrodes (ISEs). Existing
      theoretical interpretations of ISE selectivity are restricted by severe
      assumptions, such as steady state and electroneutrality, which hinder theorizing
      on this problem. For this reason, for the first time, the Nernst-Planck-Poisson
      equations are used to predict and visualize the selectivity variability over time
      and the concentration ratio. Special emphasis is placed on the non-Nernstian
      response in the measurements with liquid-ion-exchanger- and neutral-carrier-based
      ISEs. The conditions under which measured selectivity coefficients are true
      (unbiased) are demonstrated.

PMID- 17007499
TI  - Micro hot plate-based sensor array system for the detection of environmentally
      relevant gases.
AB  - A monolithic stand-alone gas sensor system is presented, which includes on a
      single chip an array of three metal oxide-coated micro hot plates with integrated
      MOS-transistor heaters, as well as a specifically designed digital system
      architecture. An octagonal-shaped micro hot plate design with MOS-transistor
      heaters has been adopted for the three gas sensors. The integrated circuitry
      includes a programmable digital temperature regulation, digital sensor readout
      units, and a standard serial interface. The programmable digital temperature
      controllers enable individual regulation of the micro hot plate temperatures in
      constant or dynamic mode. Nanocrystalline tin oxide thick films with different Pd
      dopings (undoped, 0.2 and 3 wt %) were used. Gas test measurements for
      environmentally relevant gases were carried out and evidenced detection limits of
      less than 1 ppm for carbon monoxide, or 100 ppm for methane, both at 40% relative
      humidity. Temperature modulation techniques were successfully applied for
      improved analyte discrimination.

PMID- 17007498
TI  - Exploring crown ethers as shift reagents for ion mobility spectrometry.
AB  - A series of crown ethers, 12-crown-4, 15-crown-5, 18-crown-6, and dibenzo-30
      crown-10, are examined as a possible means of shifting the mobilities of peptide
      ions. In this approach, a crown ether is added to a solution containing a mixture
      of peptides and is electrosprayed into the gas phase in order to create
      distributions of peptide-crown complexes. The ion complexes have different
      mobilities than the naked peptide ions, and the crown ether molecules appear to
      interact specifically with basic sites in the peptides thus providing some
      sequence selectivity. After the peptide-crown complexes are separated by ion
      mobility spectrometry, the ions can be collisionally activated to dissociate the
      complex (forming the naked peptide ions) prior to m/z analysis. The overall
      effect is that complex formation shifts peptide ions to different regions of the
      mobility spectrum, extending the ability to resolve components. The approach is
      illustrated by examining isobaric dipeptides as well as a combinatorial library
      containing 27 tripeptides. Cross sections for the series of crown ether ions and
      complexes that are observed are reported.

PMID- 17007500
TI  - Direct analysis of trace phenolics with a microchip: in-channel sample
      preconcentration, separation, and electrochemical detection.
AB  - A micrototal analytical method assembling in-channel preconcentration,
      separation, and electrochemical detection steps has been developed for trace
      phenolic compounds. A micellar electrokinetic chromatography separation technique
      was coupled with two preconcentration steps of field-amplified sample stacking
      (FASS) and field-amplified sample injection (FASI). An amperometric detection
      method with a cellulose-dsDNA-modified, screen-printed carbon electrode was
      applied to detect preconcentrated and separated species at the end of the
      channel. The microchip was composed of three parallel channels: first, two are
      for the sample preconcentration using FASS and FASI methods, and the third one is
      for the separation and electrochemical detection. The modification of the
      electrode surface improved the detection performance by enhancing the signal-to
      noise characteristic without surface fouling of the electrode. The method was
      examined for the analysis of eight phenolic compounds. Experimental parameters
      affecting the analytical performance of the method were assessed and optimized.
      The preconcentration factor was increased by about 5200-fold as compared with a
      simple capillary zone electrophoretic analysis using the same channel.
      Reproducible response was observed during multiple injections of samples with a
      RSD of <8.0%. The calibration plots were shown to be linear (with the correlation
      coefficient between 0.9913 and 0.9982) over the range of 0.4-600 nM. The
      sensitivity was between 0.17 +/- 0.001 and 0.48 +/- 0.006 nA/nM, with the
      detection limit of approximately 100 to approximately 150 pM based on S/N = 3.
      The applicability of the method to the direct analysis of trace phenolic
      compounds in water samples was successfully demonstrated.

PMID- 17007501
TI  - Determination of carboxyl content in high-yield kraft pulps using photoacoustic
      rapid-scan Fourier transform infrared spectroscopy.
AB  - Pinus radiata kraft pulps with varying carboxyl content were studied using
      Fourier transform infrared photoacoustic spectroscopy (FT-IR-PAS). The examined
      pulp samples, with Kappa number ranging from 20.8 to 128, originated from pulping
      experiments conducted in flow-through reactors utilizing varying effective
      alkali, temperature, and cooking time. A partial least-squares (PLS) analysis was
      used to formulate a model that correlates the spectral data with the carboxyl
      content of pulp. Using three principal components, the resultant PLS model could
      explain approximately 98.5% of the variance in the X-matrix (spectral features)
      and 96.8% of the variance in the Y-matrix (measured carboxyl content). The FT-IR
      PAS technique in combination with PLS analysis predicts the carboxyl content of
      the pulps with a high degree of accuracy. This method is much faster than the
      conventional titration methods and also not destructive to the pulp sample.

PMID- 17007503
TI  - Evanescent wave cavity ring-down spectroscopy in a thin-layer electrochemical
      cell.
AB  - The application of evanescent wave cavity ring-down spectroscopy (EW-CRDS) in
      monitoring electrogenerated species within a thin-layer electrochemical cell is
      demonstrated. In the proof-of-concept experiments described, ferricyanide,
      Fe(CN)6(3-), was produced by the transport-limited oxidation of ferrocyanide,
      Fe(CN)6(4-), in a thin-layer solution cell (25-250 microm) formed between an
      electrode and the hypotenuse of a fused-silica prism. The prism constituted one
      element of a high-finesse optical cavity arranged in a triangular ring geometry
      with light being totally internally reflected at the silica/solution interface.
      The cavity was pumped with the output (approximately 417 nm) of a single-mode
      external cavity diode laser, which was continuously scanned across the cavity
      modes. The presence of electrogenerated ferricyanide within the resulting
      evanescent field, beyond the optical interface, was detected by the enhanced loss
      of light trapped within the cavity, as measured by the characteristic cavity ring
      down. In this way, the EW-CRDS technique is sensitive to absorption in only the
      first few hundred nanometers of solution above the silica surface. The cavity
      ring-down response accompanying both cyclic voltammetric and step potential
      chronoamperometry experiments at a variety of electrode-surface distances is
      presented, and the results are shown to be well reproduced in modeling by finite
      element methods. The studies herein thus provide a foundation for further
      applications of EW-CRDS combined with electrochemistry.

PMID- 17007502
TI  - Massively parallel sample preparation for the MALDI MS analyses of tissues.
AB  - Investigation of the peptidome of the nervous system containing large, often
      easily identifiable neurons has greatly benefited from single-cell matrix
      assisted laser desorption/ionization (MALDI) mass spectrometry and has led to the
      discovery of hundreds of novel cell-to-cell signaling peptides. By combining new
      sample preparation methods and established protocols for bioanalytical mass
      spectrometry, a high-throughput, small-volume approach is created that allows the
      study of the peptidome of a variety of nervous systems. Specifically,
      approximately single-cell-sized samples are rapidly prepared from thin tissue
      slices by adhering the tissue section to a glass bead array that is anchored to a
      stretchable membrane. Stretching the membrane fragments the tissue slice into
      thousands of individual samples, their dimensions predominately governed by the
      size of the individual glass beads. Application of MALDI matrix, followed by the
      repeated condensation of liquid microdroplets on the fragmented tissue, allows
      for maximal analyte extraction and incorporation into MALDI matrix crystals.
      During extraction, analyte migration between the pieces of tissue on separate
      beads is prevented by the underlying hydrophobic substrate and by controlling the
      size of the condensation droplets. The procedure, while general in nature, may be
      tailored to the needs of a variety of analyses, producing mass spectra equivalent
      to those acquired from single-cell samples.

PMID- 17007504
TI  - Binding behavior of subphthalocyanine-tagged testosterone with human serum
      albumin at the n-hexane/water interface.
AB  - Subphthalocyaninatoboron(III) was applied for the first time as a novel marker
      tag of testosterone (Subpc-test) for the binding analysis with human serum
      albumin (HSA) at a liquid/liquid interface. The binding interaction of Subpc-test
      with HSA at the n-hexane/water interface was studied by UV-visible absorption and
      circular dichroism (CD) spectroscopy combined with a centrifugal liquid membrane
      cell at different pHs of aqueous solutions. Complementary studies by a high-speed
      stirring experiment and an interfacial tension measurement were also performed to
      characterize the interfacial adsorptivity of Subpc-test and HSA molecules,
      respectively. The n-hexane solution of Subpc-test showed no optical chirality,
      but the contact with the aqueous solution of HSA induced its optical chirality,
      clearly suggesting the formation of Subpc-test/HSA complexes at the n
      hexane/water interface. Furthermore, pH profiles of CD signals showed that the
      interaction between Subpc-test and HSA was very sensitive to the neutral-to-base
      transition (N-B transition). Interfacial formation of the Subpc-test/HSA complex
      was studied in the presence of the site-selective ligand, furosemide (site I) or
      cefaclor (site II). The experimental results suggested that Subpc-test is bound
      to site I of the HSA molecule at the n-hexane/water interface. This technique
      using subphthalocyanine as a tag molecule and the liquid/liquid interface as a
      two-dimensional nanoreaction field will be useful for the evaluation of the
      interaction between drugs or hormones and proteins.

PMID- 17007505
TI  - New role for an old probe: affinity labeling of oxylipid protein conjugates by N'
      aminooxymethylcarbonylhydrazino d-biotin.
AB  - Free radicals, electrophiles, and endogenous reactive intermediates are generated
      during normal physiological processes and are capable of modifying DNA, lipids,
      and proteins. However, elevated levels of oxidative modifications of proteins by
      reactive species are implicated in the etiology and pathology of oxidative stress
      mediated diseases, neurodegeneration, and aging. A mass spectrometry-based
      approach is reported that aids to the identification and characterization of
      carbonyl-modified proteins. The method uses N'-aminooxymethylcarbonylhydrazino d
      biotin, a biotinylated hydroxylamine derivative that forms an oxime derivative
      with the aldehyde/keto group found in oxidatively modified proteins. In this
      paper, the method is demonstrated for one class of carbonyl-modified proteins,
      namely, oxylipid peptide and protein conjugates formed by Michael addition-type
      conjugation reactions of alpha,beta-unsaturated aldehydic lipid peroxidation
      products with nucleophilic peptide side chains. This new application of an "old"
      probe, which has been used for the detection of abasic sites in DNA strands,
      introduces a biotin moiety into the oxylipid peptide conjugate. The biotin
      modified oxylipid peptide conjugate is then amenable to enrichment using avidin
      affinity capture. The described method represents an attractive alternative to
      hydrazine-based derivatization methods for oxidized peptides and proteins because
      the reduction step necessary for the transformation of the hydrazone bond to the
      chemically more stable hydrazine bond can be omitted. Tandem mass spectrometry of
      the labeled oxylipid peptide conjugates indicates that the biotin moiety is at
      least partially retained on the fragment ion during the collisionally induced
      dissociation experiments, a prerequisite for the use of automated database
      searching of uninterpreted tandem mass spectra. The reported approach is outlined
      for the detection, identification, and characterization of oxylipid peptide
      conjugates, but the labeling chemistry may also be applicable to other carbonyl
      modified proteins.

PMID- 17007506
TI  - Infrared multiphoton dissociation for enhanced de novo sequence interpretation of
      N-terminal sulfonated peptides in a quadrupole ion trap.
AB  - Infrared multiphoton dissociation (IRMPD) of N-terminal sulfonated peptides
      improves de novo sequencing capabilities in a quadrupole ion trap mass
      spectrometer. Not only does IRMPD promote highly efficient dissociation of the N
      terminal sulfonated peptides but also the entire series of y ions down to the
      y(1) fragment may be detected due to alleviation of the low-mass cutoff problem
      associated with conventional collisional activated dissociation (CAD) methods in
      a quadrupole ion trap. Commercial de novo sequencing software was applied for the
      interpretation of CAD and IRMPD MS/MS spectra collected for seven unmodified
      peptides and the corresponding N-terminal sulfonated species. In most cases, the
      additional information obtained by N-terminal sulfonation in combination with
      IRMPD provided significant improvements in sequence identification. The software
      sequence tag results were combined with a commercial database searching algorithm
      to interpret sequence information of a tryptic digest on alpha-casein s1. Energy
      variable CAD studies confirmed a 30-40% reduction in the critical energies of the
      N-terminal sulfonated peptides relative to unmodified peptides. This reduction in
      dissociation energy facilitates IRMPD in a quadrupole ion trap.

PMID- 17007507
TI  - Non-size-based membrane chromatographic separation and analysis of monoclonal
      antibody aggregates.
AB  - Humanized monoclonal antibody produced by mammalian cell culture may contain
      significant amounts of antibody dimers and smaller amounts of higher order
      aggregates. These are undesirable in therapeutic formulations, and their content
      should be lower than specific allowable limits. Quantitative analysis of
      aggregate content is usually carried out by size exclusion chromatography (SEC),
      which is slow and often gives poorly resolved peaks. We describe a novel
      hydrophobic interaction membrane chromatography-based technique for rapid, non
      size-based separation and analysis of the aggregate content in monoclonal
      antibody samples. The typical sample analysis time using this technique is less
      than 3 min, this being significantly faster than SEC. The technique gives
      excellent resolution of the antibody, its dimer, and higher order aggregates and
      could potentially be scaled up for large-scale manufacture of aggregate-free
      monoclonal antibody. This work also clearly shows that monoclonal antibody
      aggregates are more hydrophobic than the monomer form, a fact that could have
      significant theoretical and practical implications.

PMID- 17007508
TI  - Metal/polypyrrole quasi-reference electrode for voltammetry in nonaqueous and
      aqueous solutions.
AB  - As an alternative to the usual commercial reference and quasi-reference
      electrodes (QREs), we propose metal (Pt, stainless steel) coated with partially
      oxidized polypyrrole as a QRE. The electrode is easily fabricated by cyclic
      voltammetry (CV) with the metal electrode in an acetonitrile or CH2Cl2 solution
      of 10 mM pyrrole containing 0.1 M Bu4NPF6. These QREs were more stable than the
      widely used metal (e.g., Ag, Pt) wire QRE as demonstrated by testing in several
      aqueous and organic media, with the stability checked by CV with
      ferrocenemethanol as the redox species. The results obtained demonstrate good
      stability of these QREs over a period of 1 day and relatively reproducible
      potential in a given solvent and supporting electrolyte. This electrode has the
      advantage that it does not contaminate the test solution with ions or solvent
      from a usual liquid electrolyte (e.g., the KCl in an Ag/AgCl). It is also simple
      to fabricate very small electrodes for use in nanocells, e.g., in scanning
      tunneling and electrochemical microscopy.

PMID- 17007509
TI  - Detection of phosphopeptides by localized surface plasma resonance of titania
      coated gold nanoparticles immobilized on glass substrates.
AB  - We herein demonstrate a new sensing method for phosphopeptides by localized
      surface plasmon resonance (LSPR) using titania-coated gold nanoparticles
      immobilized on the surface of a glass slide as the sensing substrate and using UV
      visible spectrophotometry as the detection tool. Titania has been known to be an
      effective substrate for binding with phosphorylated species. The detection
      principle is the shift of wavelength of optical absorption due to SPR of the gold
      nanoparticles induced by binding of phosphorylated species with titania on the
      surface of the gold nanoparticles. The feasibility of the approach is
      demonstrated by detection of tryptic digest products of beta-casein and milk.
      Gold nanoparticles coated with thin films of titania, immobilized on a glass
      slide, can selectively bind traces of phosphopeptides from complex samples,
      resulting in a wavelength shift of the absorption band in the SPR spectrum with
      good reproducibility. The LSPR results are confirmed by matrix-assisted laser
      desorption/ionization mass spectrometry. The detection limit for the tryptic
      digest product of beta-casein is 50 nM.

PMID- 17007510
TI  - Antioxidant redox sensors based on DNA modified carbon screen-printed electrodes.
AB  - Antioxidant redox sensors based on DNA modified carbon screen-printed electrodes
      were developed. The carbon ink was doped with TiO2 nanoparticles, onto which
      double-strand DNA was adsorbed. A redox mediator, namely, tris-2,2'-bipyridine
      ruthenium(II) [Ru(bpy)3(2+)] was electrooxidized on the electrode surface to
      subsequently oxidize both the adsorbed ds-DNA and the antioxidants in solution.
      The resulting oxidation damage of the adsorbed ds-DNA was then detected by square
      wave voltammetry in a second solution containing only Ru(bpy)3Cl2 at a low
      concentration (microM). A kinetic model was developed to study the protecting
      role of antioxidants in aqueous solutions. The electrochemical sensor has been
      applied to evaluate the redox antioxidant capacity of different molecules.

PMID- 17007511
TI  - Amide proton back-exchange in deuterated peptides: applications to MS and NMR
      analyses.
AB  - Deuterium for hydrogen exchange at amide sites in proteins is a well-established
      means of probing the stability of certain proteins and the effects of
      interactions with ligands and other proteins. When deuterium content is analyzed
      by mass spectrometry (MS) of digested peptides, corrections frequently need to be
      made for back-exchange that occurs during digestion, separation, and analysis.
      The back-exchange process is actually complex and deserving of analysis in a
      sequence-specific manner. Here an analysis of back-exchange in the decapeptide,
      angiotensin I, and a hexapeptide derived by digestion of a 15N-labeled
      carbohydrate-binding protein, galectin-3, is presented. Nuclear magnetic
      resonance (NMR) data are used to study back-exchange at specific sites in typical
      solvents used for separation and analysis, and the derived rates are found to be
      predictable using methods established for aqueous solvents. The predictability
      provides potentially new means of improving site specificity of MS analysis and
      new means of assigning NMR resonances for deuterium content analysis in peptides.

PMID- 17007512
TI  - Voltammetric heparin-selective electrode based on thin liquid membrane with
      conducting polymer-modified solid support.
AB  - A novel, solid-supported voltammetric ion-selective electrode to detect
      anticoagulant/antithrombotic heparin at polarizable poly(vinyl chloride) (PVC)
      membrane/water interfaces was developed. An approximately 3-4.5-microm-thick PVC
      membrane plasticized with 2-nitrophenyl octyl ether was supported on a gold
      electrode modified with a poly(3-octylthiophene) (POT) film as an ion-to-electron
      transducer. Charge transport through the PVC-covered POT film is
      electrochemically reversible, as demonstrated by cyclic voltammetry with
      nonpolarizable membrane/water interfaces. In addition to the fast charge
      transport, adequate redox capacity of the POT film and a small ohmic potential
      drop in the thin PVC membrane enable ion transfer voltammetry at polarizable
      macroscopic membrane/water interfaces in a standard three-electrode cell.
      Reversible ClO4- transfer at the interfaces coupled with oxidation of a neutral
      POT film was examined by cyclic voltammetry to determine the distribution of the
      applied potential to the two polarizable interfaces by convolution technique.
      Interfacial adsorption and desorption of heparin facilitated by
      octadecyltrimethylammonium were studied also by cyclic voltammetry and
      convolution technique to demonstrate that the processes are electrochemically
      irreversible. Stripping voltammetry based on the interfacial processes gives a
      low detection limit of 0.005 unit/mL heparin in a saline solution, which is
      slightly lower than the detection limit of most sensitive heparin sensors
      reported so far (0.01 unit/mL).

PMID- 17007513
TI  - Isolated electrodeless high-frequency quartz crystal microbalance for
      immunosensors.
AB  - This paper presents a contactless technique to measure shear bulk wave resonance
      frequencies of an isolated quartz crystal in a flow cell. The line antenna placed
      outside the cell generates and detects the resonance frequencies in a wireless
      electrodeless manner. It is revealed that this mechanism relies on the
      quasistatic electric field. A 0.3-mm-thick AT-cut quartz was used, and its
      overtone resonance frequencies up to 80 MHz were measured in liquids. Exact
      vibrational analysis was carried out for a triple-layered resonator system
      consisting of the adsorbed material layer, the electrode film, and the quartz
      plate. It predicts higher frequency sensitivity to the adsorbed material at
      higher modes when the electrode layer is removed. The 13th overtone (72-MHz
      resonance frequency) was used to detect human immunoglobulin G with
      concentrations between 0.1 and 20 microg/mL captured by protein A immobilized on
      one side of the crystal. The real-time measurement of the frequency response
      yielded the equilibrium constant KA=5.21 x 10(7) M(-1).

PMID- 17007514
TI  - Detection and discrimination capabilities of a multitransducer single-chip gas
      sensor system.
AB  - The performance of a single-chip, three-transducer, complementary metal oxide
      semiconductor gas sensor microsystem has been thoroughly evaluated. The
      monolithic gas sensor system includes three polymer-coated transducers, a mass
      sensitive cantilever, a thermoelectric calorimetric sensor, and an interdigitated
      capacitive sensor that are integrated along with all electronic circuits needed
      to operate these sensors. The system additionally includes a temperature sensor
      and a serial interface unit so that it can be directly connected to, for example,
      a microcontroller. Several multitransducer chips have been coated with various
      partially selective polymers and then have been exposed to different volatile
      organic compounds. The sensitivities of the three different polymer-coated
      transducers to defined sets of gaseous analytes have been determined. The
      obtained sensitivity values have then been normalized with regard to the
      partition coefficients of the respective analyte/polymer combination to reveal
      the transducer-specific effects. The results of this investigation show that the
      three different transducers respond to fundamentally different molecular
      properties, such as the analyte molecular mass (mass-sensitive), its dielectric
      coefficient (capacitive), and its sorption heat (calorimetric) so that
      correlations between the determined sensitivity values and the different
      molecular properties of the absorbed analytes could be established. The
      information as provided by the system, hence, represents a body of orthogonal
      data that can serve as input to appropriate signal processing and pattern
      recognition techniques to address issues such as the quantification of analytes
      in mixtures.

PMID- 17007515
TI  - Capillary electrochromatography coupled to atmospheric pressure photoionization
      mass spectrometry for methylated benzo[a]pyrene isomers.
AB  - Benzo[a]pyrene, one of the most carcinogenic PAHs, has 12 monomethylated
      positional isomers (MBAPs). A strong correlation between the carcinogenicity of
      these isomers and methyl substitution has been reported. In this study, on-line
      coupling of capillary electrochromatography (CEC) and atmospheric pressure
      photoionization mass spectrometry (APPI-MS) provides a unique solution to highly
      selective separation and sensitive detection of MBAP isomers. The studies
      indicated that APPI provides significantly better sensitivity compared to
      electrospray ionization and atmospheric pressure chemical ionization modes of MS.
      A systematic investigation of APPI-MS detection parameters and CEC separation is
      established. First, several sheath liquid parameters (including type and
      concentration of volatile buffers, type and content of organic modifiers, use of
      dopants and inorganic/organic additives, and sheath liquid flow rate) and APPI-MS
      spray chamber parameters (capillary voltage, vaporizer temperature, nebulizer
      pressure) were found to have effects on detection sensitivity as well as the
      profile of mass spectrum. For example, when ammonium acetate was replaced with
      acetic acid in the sheath liquid, the MS signal was enhanced as much as 90% and
      the formation of ammonia adduct was effectively suppressed. Next, the separation
      of MBAP isomers was conducted on internal tapered columns packed with polymeric
      C18 stationary phase. With the use of a mobile phase consisting of slightly
      higher acetonitrile content (90%,v/v) and a small amount of tropylium ion, the
      analysis times were significantly shortened by 20 min without compromising the
      resolutions between the isomers. Finally, quantitative aspects of the CEC-APPI-MS
      method were demonstrated using 7-MBAP as the internal standard. The calibration
      curves of three of the most carcinogenic isomers, namely, 1-MBAP, 3-MBAP, and 11
      MBAP, showed good linearity in the range of 2.5-50 microg/mL with a limit of
      detection at 400 ng/mL.

PMID- 17007516
TI  - Optically trapping confocal Raman microscopy of individual lipid vesicles:
      kinetics of phospholipase A(2)-catalyzed hydrolysis of phospholipids in the
      membrane bilayer.
AB  - Phospholipase A2 (PLA2)-catalyzed hydrolysis at the sn-2 position of 1,2
      dimyristoyl-sn-glycero-3-phosphocholine in optically trapped liposomes is
      monitored in situ using confocal Raman microscopy. Individual optically trapped
      liposomes (0.6 microm in diameter) are exposed to PLA2 isolated from cobra (Naja
      naja naja) venom at varying enzyme concentrations. The relative Raman scattering
      intensities of C-C stretching vibrations from the trans and gauche conformers of
      the acyl chains are correlated directly with the extent of hydrolysis, allowing
      the progress of the reaction to be monitored in situ on a single vesicle. In
      dilute vesicle dispersions, the technique allows the much higher local
      concentration of lipid molecules in a single vesicle to be detected free of
      interferences from the surrounding solution. Observing the local composition of
      an optically trapped vesicle also allows one to determine whether the products of
      enzyme-catalyzed hydrolysis remain associated with the vesicle or dissolve into
      solution. The observed reaction kinetics exhibited a time lag prior to the rapid
      hydrolysis. The lag time varied inversely with the enzyme concentration, which is
      consistent with the products of enzyme-catalyzed lipid hydrolysis reaching a
      critical concentration that allows the enzyme to react at a much faster rate. The
      turnover rate of membrane-bound enzyme determined by Raman microscopy during the
      rapid, burst-phase kinetics was 1200 s(-1). Based on previous measurements of the
      equilibrium for PLA2 binding to lipid membranes, the average number of enzyme
      molecules responsible for catalyzing the hydrolysis of lipid on a single
      optically trapped vesicle is quite small, only two PLA2 molecules at the lowest
      enzyme concentration studied.

PMID- 17007517
TI  - Real-time detection of kinetic germination and heterogeneity of single Bacillus
      spores by laser tweezers Raman spectroscopy.
AB  - Germination is the process by which a dormant spore returns to its vegetative
      state when exposed to suitable conditions. We report on the real-time detection
      of kinetic germination and heterogeneity of single Bacillus thuringiensis spores
      in an aqueous solution by monitoring the calcium dipicolinate (CaDPA) biomarker
      with laser tweezers Raman spectroscopy (LTRS). A single B. thuringiensis spore
      was optically trapped in a focused laser beam, and its Raman spectra were
      recorded sequentially in time after exposure to a nutrient-rich medium, so that
      the CaDPA amount inside the trapped spore was monitored during the dynamic
      germination process. The CaDPA content in an individual spore was observed to
      remain almost constant in the first period and then decrease very rapidly due to
      its release into the medium (within approximately 2 min). The time-to-germination
      (t(germ)), defined as the time required for the CaDPA band intensity to decrease
      to the midpoint from its initial value, was found to be stochastic for individual
      spores with a typical value of approximately 30 min under the experimental
      conditions. The distribution of the time-to-germination was measured from a time
      lapse measurement of a population of spores. The results demonstrated that LTRS
      can be used to noninvasively detect the kinetic germination process at the single
      cell level and explore cellular heterogeneity.

PMID- 17007518
TI  - Evaporation of water from particles in the aerodynamic lens inlet: an
      experimental study.
AB  - The extremely high particle transmission efficiency of aerodynamic lens inlets
      resulted in their wide use in aerosol mass spectrometers. One of the consequences
      of transporting particles from high ambient pressure into the vacuum is that it
      is accompanied by a rapid drop in relative humidity (RH). Since many atmospheric
      particles exist in the form of hygroscopic water droplets, a drop in RH may
      result in a significant loss of water and even a change in phase. How much water
      is lost in these inlets is presently unknown. Since water loss can affect
      particle size, transmission efficiency, ionization probability, and mass
      spectrum, it is imperative to provide definitive experimental data that can serve
      to guide the field to a reasonable and uniform sampling approach. In this study,
      we present the results of a number of highly resolved measurements, conducted
      under well-defined conditions, of water evaporation from a range of particles,
      during their transport through an aerodynamic lens inlet. We conclude that the
      only sure way to avoid ambiguities during measurements of aerodynamic diameter in
      instruments that utilize low-pressure aerodynamic lens inlets is to dry the
      particles prior to sampling.

PMID- 17007520
TI  - Parts per billion doping and characterization of uranium distribution in an epoxy
      polymer matrix.
AB  - Formulating an epoxy polymer provides a broadly applicable method for
      homogeneously doping a chemically stable, particulate-resistant, and radiation
      hardened matrix with virtually any trace elements of interest. In the example
      reported, control of uranium levels over the range, 15 microg/g-15 ng/g, is
      demonstrated. Fission track density determinations, referenced to NIST SRMs,
      indicate +/-5% variations in lateral uranium distributions. Determinations of
      levels of uranium impurities in commercially available high-purity samples of
      graphite, fused silica, and aluminum show respective nanogram per gram ranges of
      3 +/- 0.1-5 +/- 0.3, 3 +/- 0.8-27 +/- 2, and 113 +/- 11-546 +/- 11. The prepared
      polymer materials cover 3 orders of magnitude of uranium levels in an ideal
      matrix. This accomplishes the prerequisite for subsequent investigations of the
      chemistry occurring at fission fragment-induced damage sites of selected track
      registering materials as a function of controlled reactive site densities. The
      matrix also serves as a source of swift heavy ions for creating nanoscale
      features in dielectric materials.

PMID- 17007519
TI  - Capillary electrophoresis separation in the presence of an immiscible boundary
      for droplet analysis.
AB  - This paper demonstrates the ability to use capillary electrophoresis (CE)
      separation coupled with laser-induced fluorescence for analyzing the contents of
      single femtoliter-volume aqueous droplets. A single droplet was formed using a T
      channel (3 microm wide by 3 microm tall) connected to microinjectors, and then
      the droplet was fluidically moved to an immiscible boundary that isolates the CE
      channel (50 microm wide by 50 microm tall) from the droplet generation region.
      Fusion of the aqueous droplet with the immiscible boundary effectively injects
      the droplet content into the separation channel. In addition to injecting the
      contents of droplets, we found aqueous samples can be introduced directly into
      the separation channel by reversibly penetrating and resealing the immiscible
      partition. Because droplet generation in channels requires hydrophobic surfaces,
      we have also investigated the advantages to using all hydrophobic channels versus
      channel systems with patterned hydrophobic and hydrophilic regions. To fabricate
      devices with patterned surface chemistry, we have developed a simple strategy
      based on differential wetting to deposit selectively a hydrophilic polymer
      (poly(styrenesulfonate)) onto desired regions of the microfluidic chip. Finally,
      we applied our device to the separation of a simple mixture of fluorescein
      labeled amino acids contained within a approximately 10-fL droplet.

PMID- 17007521
TI  - Carbon nanofiber electrodes and controlled nanogaps for scanning electrochemical
      microscopy experiments.
AB  - The electrochemical behavior of electrodes made by sealing carbon nanofibers in
      glass or with electrophoretic paint has been studied by scanning electrochemical
      microscopy (SECM). Because of their small electroactive surface area, conical
      geometry with a low aspect ratio and high overpotential for proton and oxygen
      reduction, carbon nanofiber (CNF) electrodes are promising candidates for
      producing electrode nanogaps, imaging with high spatial resolution and for the
      electrodeposition of single metal nanoparticles (e.g., Pt, Pd) for studies as
      electrocatalysts. By using the feedback mode of the SECM, a CNF tip can produce a
      gap that is smaller than 20 nm from a platinum disk. Similarly, the SECM used in
      a tip-collection substrate-generation mode, which subsequently shows a feedback
      interaction at short distances, makes it possible to detect a single CNF by
      another CNF and then to form a nanometer gap between the two electrodes. This
      approach was used to image vertically aligned CNF arrays. This method is useful
      in the detection in a homogeneous solution of short-lifetime intermediates, which
      can be electrochemically generated at one electrode and collected at the second
      at distances that are equivalent to a nanosecond time scale.

PMID- 17007522
TI  - Nanoparticle probes with surface enhanced Raman spectroscopic tags for cellular
      cancer targeting.
AB  - We have developed biocompatible, photostable, and multiplexing-compatible surface
      enhanced Raman spectroscopic tagging material (SERS dots) composed of silver
      nanoparticle-embedded silica spheres and organic Raman labels for cellular cancer
      targeting in living cells. SERS dots showed linear dependency of Raman signatures
      on their different amounts, allowing their possibility for the quantification of
      targets. In addition, the antibody-conjugated SERS dots were successfully applied
      to the targeting of HER2 and CD10 on cellular membranes and exhibited good
      specificity. SERS dots demonstrate the potential for high-throughput screening of
      biomolecules using vibrational information.

PMID- 17007523
TI  - Sensitive immunoassay of a biomarker tumor necrosis factor-alpha based on
      poly(guanine)-functionalized silica nanoparticle label.
AB  - A novel electrochemical immunosensor for the detection of tumor necrosis factor
      alpha (TNF-alpha) based on poly(guanine)-functionalized silica nanoparticles
      (NPs) label is presented. The detection of mouse TNF-alpha via immunological
      reaction is based on a dual signal amplification: (1) a large amount of guanine
      residues introduced on the electrode surface through sandwich immunoreaction and
      poly(guanine)-functionalized silica NP label; (2) Ru(bpy)3(2+)-induced catalytic
      oxidation of guanine, which results in great enhancement of anodic current. The
      synthesized silica NP conjugates were characterized with atomic force microscopy,
      X-ray photoelectron spectroscopy, and electrochemistry. These experiments
      confirmed that poly(guanine) and avidin were immobilized on the surface of silica
      NPs. The performance of the electrochemical immunosensor was evaluated and some
      experiment parameters (e.g., concentration of Ru(bpy)3(2+), incubation time of
      TNF-alpha, etc.) were optimized. The detection limit for TNF-alpha is found to be
      5.0 x 10(-11) g mL(-1) (2.0 pM), which corresponds to 60 amol of TNF-alpha in 30
      microL of sample. This immunosensor based on the poly(guanine)-functionalized
      silica NP label offers great promise for rapid, simple, cost-effective analysis
      of biological samples.

PMID- 17007524
TI  - Ionic liquid high-temperature gas sensor array.
AB  - A novel sensor array using seven room-temperature ionic liquids (ILs) as sensing
      materials and a quartz crystal microbalance (QCM) as a transducer was developed
      for the detection of organic vapors at ambient and elevated temperatures.
      Ethanol, dichloromethane, benzene, and heptane were selected as representative
      gas analytes for various kinds of environmental pollutants and common industrial
      solvents. The QCM/IL sensors responded proportionately and reversibly to the
      organic vapor concentrations (i.e., ethanol, heptane, and benzene) in the gas
      phase from 0 to 100% saturation at room and elevated temperatures (e.g., 120
      degrees C) but deviated from this linear relationship at high concentrations for
      dichloromethane, a highly volatile compound. Linear discriminant analysis was
      used to analyze the sensing patterns. Excellent classifications were obtained for
      both known and unknown concentrations of vapor samples. The correct
      classifications were 100% for known concentration samples and 96% for samples
      with unknown concentrations. Thermodynamics and ATR-FT-IR studies were conducted
      to understand specific molecular interactions, the strength of the interaction
      between ILs and organic vapors, and the degree of ordering that takes place upon
      dissolution of the vapors in ILs. The different response intensity of the QCM/IL
      sensors to the organic vapors depends on the different solubilities of organic
      vapors in ILs and varying molecular/ion interactions between each organic vapor
      and IL. The diverse set of IL studied showed selective responses due to
      structural differences. Therefore, a sensor array of ILs would be able to
      effectively differentiate different vapors in pattern recognitions, facilitating
      discrimination by their distinctive patterns in response to organic vapors in
      both room and high temperatures.

PMID- 17007525
TI  - Subsecond voltammetric separation between dopamine and serotonin in the presence
      of ascorbate.
AB  - Although voltammetry has proved an important tool for unraveling the dynamics of
      specific neurotransmitter molecules during the past decade, it has been very
      difficult to monitor more than one neurotransmitter simultaneously. In this work,
      we present a voltammetric methodology that allows discrimination between dopamine
      and serotonin, two important neurotransmitter molecules with very similar
      electrochemical properties, in the presence of high concentrations of ascorbate.
      We combined the application of a novel large-amplitude/high-frequency voltage
      excitation with signal processing techniques valid for the analysis of
      nonstationary and nonlinear phenomena. This allows us to minimize the
      contribution from capacitance and preserve the faradaic features of the
      voltammetric response providing us with excellent voltammetric detail. Using
      appropriate voltage excitation parameters and defining specific regions in the
      voltage space, so-called voltage windows, we can measure the concentrations of
      dopamine and serotonin separately or independently in mixed solutions even in the
      presence of high concentrations of ascorbate. Because of the enhanced
      voltammetric detail of this new technique, it is also possible to explore effects
      attributed to interfacial phenomena such as adsorption/desorption and electrode
      fouling.

PMID- 17007526
TI  - Flow-through multianalyte chemiluminescent immunosensing system with designed
      substrate zone-resolved technique for sequential detection of tumor markers.
AB  - A novel flow-through immunosensing system for performing a multianalyte
      chemiluminescent determination in a single run was designed. A new analytical
      strategy of substrate zone-resolved technique was proposed. Using carcinoma
      antigen 125 (CA 125) and carcinoembryonic antigen (CEA) as model analytes, the
      capture antibodies for CA 125 and CEA were immobilized on an UltraBind aldehyde
      activated membrane to act as an immunoreactor, to which the mixture of CA 125,
      CEA, and their corresponding tracers, horseradish peroxidase (HRP)-labeled anti
      CA 125 and alkaline phosphatase (ALP)-labeled anti-CEA, was introduced for on
      line incubation. The substrates for HRP and ALP were then delivered into the
      detection cell sequentially to perform substrate zone-resolved immunoassay by a
      sandwich format. Under optimal conditions, CA 125 and CEA could be assayed in the
      ranges of 5.0-100 units/mL and 1.0-120 ng/mL, respectively. The whole assay
      process including incubation, wash, detection, and regeneration could be
      completed in 35 min. The serum samples from the clinic were assayed with the
      proposed method, and the results were in acceptable agreement with the reference
      values. This method and the strategy of substrate zone-resolved technique could
      be further developed for high-throughput multianalyte immunoassay.

PMID- 17007527
TI  - Assessment of the electrochemical behavior of two-dimensional networks of single
      walled carbon nanotubes.
AB  - Scanning electrochemical microscopy (SECM) has been employed in the feedback mode
      to assess the electrochemical behavior of two-dimensional networks of single
      walled carbon nanotubes (SWNTs). It is shown that, even though the network
      comprises both metallic and semiconducting SWNTs, at high density (well above the
      percolation threshold for metallic SWNTs) and with approximately millimolar
      concentrations of redox species the network behaves as a thin metallic film,
      irrespective of the formal potential of the redox couple. This result is
      particularly striking since the fractional surface coverage of SWNTs is only
      approximately 1% and SECM delivers high mass transport rates to the network.
      Finite element simulations demonstrate that under these conditions diffusional
      overlap between neighboring SWNTs is significant so that planar diffusion
      prevails in the gap between the SECM tip and the underlying SWNT substrate. The
      SECM feedback response diminishes at higher concentrations of the redox species.
      However, wet gate measurements show that at the solution potentials of interest
      the conductivity is sufficiently high that lateral conductivity is not expected
      to be limiting. This suggests that reaction kinetics may be a limiting factor,
      especially since the low surface coverage of the SWNT network results in large
      fluxes to the SWNTs, which are characterized by a low density of electronic
      states. For electroanalytical purposes, significantly, two-dimensional SWNT
      networks can be considered as metallic films for typical millimolar
      concentrations employed in amperometry and voltammetry. Moreover, SWNT networks
      can be inexpensively and easily formed over large scales, opening up the
      possibility of further electroanalytical applications.

PMID- 17007528
TI  - Detection of organophosphorus compounds by covalently immobilized
      organophosphorus hydrolase.
AB  - As a consequence of organophosphorus (OP) toxins posing a threat to human life
      globally, organophosphorus hydrolase (OPH) has become the enzyme of choice to
      detoxify such compounds. Organophosphorus hydrolase was covalently immobilized
      onto a quartz substrate for utilization in paraoxon detection. The substrate was
      cleaned and modified prior to chemical attachment. Each modification step was
      monitored by imaging ellipsometry as the thickness increased with each
      modification step. The chemically attached OPH was labeled with a fluorescent dye
      (7-isothiocyanato-4-methylcoumarin) for the detection of paraoxon in aqueous
      solution, ranging from 10(-9) to 10(-5) M. UV-visible spectra were also acquired
      for the determination of the hydrolysis product of para-oxon, namely p
      nitrophenol.

PMID- 17007529
TI  - Enzyme-nanoparticle functionalization of three-dimensional protein scaffolds.
AB  - Various surface modification techniques have been developed for patterning
      functional biomolecules in two dimensions, allowing enzymes, antibodies, and
      other compounds to be localized for applications in bioanalysis and
      bioengineering. Here, we report a strategy for extending high-resolution
      patterning of biomolecules to three dimensions. In this approach, three
      dimensional protein scaffolds are created by a direct-write process in which
      multiphoton excitation promotes photochemical cross-linking of protein molecules
      from aqueous solution within specified volume elements. After scaffold
      fabrication, protein microstructures are functionalized with enzyme-gold
      nanoparticle conjugates via a targeting process based in part on electrostatic
      attraction between the low-isoelectric-point enzyme and the microstructure,
      fabricated from high-isoelectric-point proteins. High signal-to-background ratios
      (approximately 20:1) are demonstrated for fluorescent product streams created by
      dephosphorylation of the fluorogenic compound, fluorescein diphosphate, at
      microstructures decorated with alkaline phosphatase-gold nanoparticle conjugates.
      We also demonstrate feasibility for using such structures to quantify substrate
      concentrations in flowing streams with low-micromolar detection limits and to
      create sensor suites based on both enzyme-nanoparticle functionalization and
      intrinsic enzymatic activity of protein scaffolds. These topographically complex
      sensors and dosing sources have potential applications in microfluidics, sensor
      array fabrication, and real-time chemical modification of cell culture
      environments.

PMID- 17007531
TI  - Fabrication and characterization of submicrometer- and nanometer-sized double
      barrel pipets.
AB  - Submicro- and nanometer-sized glass double-barrel pipets have been fabricated by
      a laser puller with new pulling programs and have been used to support submicro-
      and nanometer dual liquid/liquid interfaces. The smallest pipet that can be made
      by this approach is approximately 20 nm in radius. These pipets have been
      characterized by cyclic voltammetry and scanning electron microscopy.
      Generation/collection mode of charge-transfer reaction is demonstrated at the
      submicro- and nanometer dual-liquid/liquid interfaces. The dependence of
      collection efficiency upon geometric parameters of the pipets has been discussed.
      Among the micro-, submicro-, and nanopipets, we have found that the submicro
      double-barrel pipets have higher collection efficiencies than that of others and
      are also very close to the values predicted by the theory. Therefore, in terms of
      G/C mode applications, the optimal size of double-barrel pipets should be in
      submicrometer scale. As one of the examples of special application, we have also
      demonstrated that in the case of no supporting electrolyte, only the nanometer
      double-barrel pipets can provide reasonably good G/C results.

PMID- 17007530
TI  - Nonretentive solid-phase extraction of phosphorylated peptides from complex
      peptide mixtures for detection by matrix-assisted laser desorption/ionization
      mass spectrometry.
AB  - Widespread interest in protein phosphorylation has led to the development of a
      variety of methods for the analysis of phosphoproteomes of different types of
      organisms. Many applications involve pretreatment of the sample before mass
      spectrometric measurement and can crucially improve the detection efficiency of
      individual phosphopeptides. Despite intense research efforts, separation and
      extraction of phosphorylated peptides, especially multiphosphorylated ones,
      remain challenging tasks and need to be further explored and expanded with
      unconventional approaches. In this study, we describe the application of
      nonretentive solid-phase extraction (SPE) to the analysis of phosphopeptides
      using the highly cross-linked polystyrene-divinylbenzene material Strata-X. This
      study indicates that the procedure allows for the preferential extraction of
      phosphopeptides regardless of their extent of phosphorylation. The Strata-X
      material primarily retains nonphosphorylated peptides by hydrophobic interaction,
      whereas the inherent hydrophilicity of phosphorylated peptides leads to their
      partitioning into the aqueous phase. Phosphopeptides that were rapidly segregated
      out of tryptic digest mixtures and collected in the early aqueous fractions
      generated intense signals in mass spectra. The method was developed using SPE
      Strata-X columns, then suited for detection and sequencing of phosphopeptides by
      miniaturizing the system to the scale of custom-made microcolumns. This provided
      fast isolation of phosphopeptides from protein digests along with direct MALDI on
      target deposition. The possibility of on-target washing during sample preparation
      is also presented.

PMID- 17007532
TI  - Observation of chemical reactions at the solid-water interface by quick XAFS
      combined with a column reactor.
AB  - A simple method for the observation of the kinetics of the reactions at the solid
      water interface was developed using quick X-ray absorption fine structure
      combined with a column reactor. We applied the method to the oxidation reaction
      of As(III) by manganese oxide, a strong oxidizer in natural systems. A reliable
      reaction rate constant k', 3.9 x 10(-4) %(-1) min(-1) at pH 7.1, was obtained,
      where the effect of photooxidation under X-ray beam can be eliminated.
      Considering the average Mn/As molar ratio in the system, the value is reasonable
      compared with other reported values. Since this method is very simple, we can
      apply it to various elements and reaction systems at the solid-water interface as
      a tool to understand the kinetics of various reactions in detail.

PMID- 17007533
TI  - Acid stability of carbon paste enzyme electrodes.
AB  - This note reports on the unusual protection of several enzymes against harsh pH
      conditions provided by carbon paste electrodes. Both glucose oxidase and
      polyphenol oxidase carbon paste amperometric biosensors display a remarkable
      resistance to acid deactivation compared to conventional biosensors prepared by
      electropolymeric entrapment of enzymes. For example, the carbon paste enzyme
      electrodes fully retain their activity upon stressing in strongly acidic
      conditions (pH approximately 2.0-2.5) for prolonged periods, where conventional
      (polymer-based) biosensors rapidly lose most of their response. Such unusual acid
      stability of carbon paste enzyme electrodes is attributed to the "pH memory" of
      enzymes in the hydrophobic paste environment, to the barrier to hydronium ions
      provided by the pasting liquid and to decreased conformational mobility.

PMID- 17007534
TI  - Electrochemical characterization of recessed nanodisk-array electrodes prepared
      from track-etched membranes.
AB  - Recessed nanodisk-array electrodes (RNEs) fabricated from track-etched
      polycarbonate membranes (TEPCMs) having cylindrical nanopores (50 nm in diameter)
      were characterized using cyclic voltammetry (CV). Such electrodes were prepared
      by depositing a gold thin film onto a TEPCM via sputtering or thermal
      evaporation. CV of the RNEs showed the transition from linear to radial diffusion
      modes of redox-active molecules with decreasing scan rate. The resulting change
      in maximum faradic current, which is the peak current in a peak-shaped CV and the
      plateau current in a sigmoidal CV, provides a simple means for calculating the
      pore length and effective pore density within a RNE. This method permits us to
      assess the completeness of the seal between a TEPCM and gold film as well as the
      extent to which air bubbles block the nanopores.

PMID- 17007535
TI  - Electroenzymatic polypyrrole-intercalator sensor for the determination of West
      Nile virus cDNA.
AB  - The chemical binding of a redox acridone derivative onto a polypyrrole film
      functionalized by N-hydroxysuccinimide groups provided an electrode capable of
      anchoring DNA duplex by simple insertion of the grafted acridone intercalator
      into the dsDNA solution. This electrode was applied for the detection of a ssDNA
      derived from a West Nile virus sequence. The latter was thus amperometrically
      detected after its hybridization in solution with a biotinylated complementary
      oligonucleotide followed by its anchoring and labeling by a glucose oxidase at 1
      pg/mL.

PMID- 17007536
TI  - Supercritical fluid chromatography reduction of hydrogen/deuterium back exchange
      in solution-phase hydrogen/deuterium exchange with mass spectrometric analysis.
AB  - The single biggest problem with solution-phase H/D exchange as a mass
      spectrometric probe of surface exposure in a protein (or protein complex) is back
      exchange of H for D after the initial H/D exchange has been quenched. Back
      exchange results in loss of pertinent data and also greatly hampers data
      analysis. Previously, very fast, cold (0-4 degrees C) HPLC was performed to help
      reduce back-exchange, but calculated back-exchange still averages approximately
      30%. In this report, supercritical fluid chromatography replaces HPLC as the
      desalting/separation technique prior to mass analysis, providing a dramatic
      reduction in back-exchange compared to the fast, cold HPLC methods.

PMID- 17007537
TI  - Synthesis, characterization, and application of chiral ionic liquids and their
      polymers in micellar electrokinetic chromatography.
AB  - Two amino acid-derived (leucinol and N-methylpyrrolidinol) chiral ionic liquids
      are synthesized and characterized in both monomeric and polymeric forms. Leucinol
      based chiral cationic surfactant is a room-temperature ionic liquid, and
      pyrrolidinol-based chiral cationic surfactant melts at 30-35 degrees C to form an
      ionic liquid (IL). The monomeric and polymeric ILs are thoroughly characterized
      to determine critical micelle concentration, aggregation number, polarity,
      optical rotation, and partial specific volume. Herein, we present the first
      enantioseparation using chiral IL as a pseudostationary phase in capillary
      electrophoresis. Chiral separation of two acidic analytes, (+/-)-alpha
      bromophenylacetic acid and (+/-)-2-(2-chlorophenoxy)propanoic acid (+/-)-(2-PPA)
      can be achieved with both monomers and polymers of undecenoxycarbonyl-L
      pryrrolidinol bromide (L-UCPB) and undecenoxycarbonyl-L-leucinol bromide (L-UCLB)
      at 25 mM surfactant concentration using phosphate buffer at pH 7.50. The chiral
      recognition seems to be facilitated by the extent of interaction of the acidic
      analytes with the cationic headgroup of chiral selectors. Polysodium N
      undecenoxycarbonyl-L-leucine sulfate (poly-L-SUCLS) and polysodium N
      undecenoxycarbonyl-L-leucinate (poly-L-SUCL) were compared at high and low pH for
      the enantioseparation of (+/-)-(2-PPA). At pH 7.5, poly-L-SUCLS, poly-L-SUCL, and
      (+/-)-(2-PPA) are negatively charged resulting in no enantioseparation. However,
      chiral separation was observed for (+/-)-(2-PPA) using poly-L-SUCLS at low pH (pH
      2.00) at which the analyte is neutral. The comparison of chiral separation of
      anionic and cationic surfactants demonstrates that the electrostatic interaction
      between the acidic analyte and cationic micelle plays a profound role in
      enantioseparation.

PMID- 17007538
TI  - Role of bacterial superantigens in atopic dermatitis : implications for future
      therapeutic strategies.
AB  - The role of staphylococcal superantigens in the pathophysiology of atopic
      dermatitis (AD) has been the focus of intense interest during the past decade.
      Although the increased prevalence of Staphylococcus aureus and its bacterial
      toxins in AD skin is well established, exploitation of the known mechanisms of
      superantigens in this disease for the development of novel therapies remains an
      active area of research. With the emergence of multi-drug resistant S. aureus,
      the need for a better understanding of the pathophysiology of bacterial
      superantigens in AD has become increasingly important. This review examines the
      mechanisms of S. aureus colonization and infection, of which the most important
      are defective skin barrier function, increased S. aureus adherence, and the
      decreased innate immune responses found in AD skin. The contribution of
      superantigens to the pathophysiology of AD is then discussed. Important
      immunologic mechanisms in this context include the role of superantigens in
      promoting T helper-2 skin inflammation, IgE production, T-regulatory cell
      subversion, expansion and migration of skin-homing T cells, and IgE anti
      superantigen production. Lastly, these findings are discussed with reference to
      current therapeutic approaches, of which the most important include anti
      inflammatory and antimicrobial medications, and future strategies, which are
      expected to consist of immune-modulators and synthetic antibacterials.

PMID- 17007539
TI  - Persistent acne in women : implications for the patient and for therapy.
AB  - Acne is traditionally regarded as a skin disorder of the teenage years. However,
      recent epidemiologic studies have shown that a significant number of female
      patients aged >25 years experience acne. One recent community-based UK study
      estimated the prevalence of facial acne in adult women aged between 26 and 44
      years to be 14%. It is not clear whether there is a true increase in acne in this
      age group or whether these patients are less tolerant of their acne and/or better
      informed of available therapies and so seek advice. The reasons for persistent
      acne are not fully understood. External factors such as use of certain cosmetics,
      ingestion of drugs, and endocrine abnormalities should all be considered when
      managing these patients. Post-adolescent acne in females can be divided into
      'persistent acne', which represents a continuation of acne from adolescence into
      adult life, and 'late-onset' acne, which describes significant acne occurring
      sometimes for the first time after the age of 25 years. The clinical picture of
      each of these forms of acne in adult females can differ slightly from
      conventional adolescent disease. The course of each form is more indolent.
      Because of these variations, the approach to investigation and management of
      these cases may have subtle differences when compared with that for teenage
      disease. Acne treatment should aim to reduce sebum, comedogenesis,
      propionibacteria population, and inflammation. Treatment selection will depend on
      the acne grade and site as well as the patient's preference and ability to comply
      with therapy. Maintenance therapy plays an important role in managing this group
      of patients. As the response to treatment is inevitably slow, patients must be
      encouraged to adhere to the chosen treatment regimen. This article reviews the
      literature on persistent acne in women in terms of clinical presentation and
      possible etiologic factors, and outlines principles of therapy related to
      managing these cases.

PMID- 17007540
TI  - Cutaneous manifestations of syphilis : recognition and management.
AB  - After a marked decline in the number of syphilis cases in the context of AIDS
      prevention campaigns, a significant increase has been observed in states of the
      former Soviet Union since 1994. In recent years, outbreaks have also been
      reported in the US, Canada, and several European countries. The current epidemic
      in the US and in different parts of Europe has largely involved men who have sex
      with men, many of whom are infected with HIV. Since a misdiagnosis of syphilis
      can have serious consequences for the patient and also for pregnancies and
      newborns, clinicians should be aware of the many manifestations of syphilis and
      difficulties in the diagnosis and management of the disease. Younger clinicians
      in particular are no longer familiar with the diverse clinical symptoms and the
      complex diagnostics of syphilis. Patients co-infected with HIV may present with
      atypical clinical manifestations and laboratory test results. Furthermore,
      through its association with an increased risk of HIV infection, syphilis has
      acquired a new potential for morbidity and mortality, and the diagnosis of
      syphilis should be routinely considered in patients with uveitis, sudden
      deafness, aortic thoracic aneurysm, or pregnancy. Only a minority of syphilis
      infections are detected in the primary stage. This may be because of atypical
      locations and, occasionally, atypical morphology of the lesions; however, it may
      also be because of the difficulty of detecting the pathogen. In the secondary
      stage, which is clinically extremely diverse, the diagnosis is confirmed
      serologically. There is a need for increased awareness of the symptoms and signs
      of acute infections, together with a willingness to consider the diagnosis of
      syphilis in patients with vague symptoms. An increasing number of diagnostic
      tests (both specific and nonspecific) are now available. However, in the absence
      of clinical symptoms or in cases with a low titer or inconsistent test results,
      diagnosis of syphilis can be difficult or even impossible. Treatment and follow
      up should follow current guidelines designed for the involved area. In this
      article, the cutaneous manifestations of syphilis and their diagnostic and
      therapeutic management are described in detail.

PMID- 17007541
TI  - Confluent and reticulated papillomatosis : a review of the literature.
AB  - Confluent and reticulated papillomatosis (CARP) was first described >60 years
      ago. It is distinct from acanthosis nigricans. This article presents the results
      of a review of the literature in MEDLINE through May 2006 using the terms
      'confluent and reticulated papillomatosis', 'reticulated and confluent
      papillomatosis of Gougerot and Carteaud', and 'reticulated papillomatosis'. A
      recent report has linked the presence of Dietzia spp. (family: Dietziaceae;
      suborder: Corynebacterineae; order: Actinomycetales) in the skin to CARP. CARP
      has also been linked to defects in keratinization. Other possible causes of CARP
      that have been suggested but seem less likely include endocrine abnormalities,
      Pityrosporum, a reaction to UV light, and a variation of cutaneous amyloidosis.
      CARP has been reported worldwide and occurs in both sexes, all age groups, and
      all races. The disorder can initially manifest as hyperkeratotic or verrucous
      papules that coalesce to form a reticular pattern peripherally and confluent
      plaques centrally. Although a variety of treatments for CARP exist, oral
      minocycline 50-100mg twice daily has been the preferred treatment. However,
      recent reports of the effectiveness of azithromycin 250-500mg three times weekly
      may make azithromycin the preferred treatment for CARP, since it has a more
      benign adverse effect profile than minocycline. Other effective antibacterial
      treatments include fusidic acid 1000mg daily, clarithromycin 500mg daily,
      erythromycin 1000mg daily, tetracycline 500mg twice daily, and cefdinir 300mg
      twice daily. If a recent finding that CARP is caused by a bacterial microorganism
      is replicated, treatment should likely be determined by bacterial sensitivities,
      antibacterial adverse effect profiles, and cost considerations. Other oral
      treatments of CARP that are effective but currently disfavored because of the
      effectiveness of minocycline include isotretinoin, acitretin, and etretinate.
      There have been mixed reports regarding the effectiveness of topical treatments,
      which include selenium sulfide, ketoconazole cream, tretinoin, tazarotene,
      tacalcitol, and calcipotriene (calcipotriol).

PMID- 17007542
TI  - Mycetoma : a review.
AB  - Mycetoma is a chronic granulomatous infection that is present worldwide and
      endemic in tropical and subtropical regions. The infection is caused by the
      traumatic inoculation of a fungus (eumycetoma) or a bacterium (actinomycetoma)
      and generally remains localized, causing cutaneous and subcutaneous tissue
      swelling, nodule formation, and drainage through sinus tracts. This review
      details the history of mycetoma, which may date as far back as the Byzantine
      period (300-600 AD), the epidemiology of the disease, which is characterized by
      an endemic region located between the latitudes of 15 degrees south and 30
      degrees north, and the clinical presentation and treatment of mycetoma, focusing
      on the differences between eumycete and actinomycete infections. Diagnosis is
      established by identifying the type of grains found in the discharge, which
      guides treatment. Mycetoma caused by bacteria can usually be managed effectively
      with antibacterial medication alone, while infections with fungi require
      antifungal medication and surgery. Without proper treatment, mycetoma can lead to
      deformity, amputation, and death.

PMID- 17007543
TI  - Collagen fibril arabesques in connective tissue disorders.
AB  - BACKGROUND: In various connective tissue disorders, collagen fibrils and elastic
      fibers may exhibit some ultrastructural abnormalities. OBJECTIVE: This electron
      microscopy study focused on collagen fibril orientation and unusual shapes in the
      dermis of Ehlers-Danlos syndrome (EDS) and related entities, including
      spontaneous cervical artery dissection syndrome and recurrent preterm premature
      rupture of fetal membranes syndrome. RESULTS: In addition to some abnormal fibril
      shapes typically found in these syndromes, other conformations (hook shaped, S
      shaped, ring shaped) that have not been illustrated previously in the literature
      were observed. CONCLUSION: The abnormal collagen fibril conformations observed in
      EDS and other related conditions characterized by tissue fragility likely affect
      both the internal cohesiveness of the bundles and the mechanobiologic properties
      of the tissue.

PMID- 17007544
TI  - Oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis :
      case reports and review of the literature.
AB  - Inflammatory flare-up reactions of some dermatomycoses, particularly those caused
      by zoophilic fungi, are typical and potentially severe adverse effects following
      the intake of some oral antifungals. However, this condition has not previously
      been reported with the most frequently used antifungals in dermatology, namely
      fluconazole, itraconazole, and terbinafine. In this report, we describe five
      patients, observed over a 10-year period, who presented with inflammatory
      exacerbations following oral antifungal therapy for dermatomycoses. We also
      review the literature on inflammatory reactions exacerbated by oral antifungal
      agents. Details of the patients' age, sex, occupation, and atopic background; the
      site of the lesion, its clinical and histologic features, and any systemic signs;
      the identity of the fungal pathogen; the antifungal agent taken by the patient;
      the time between drug intake and occurrence of the flare-up; the approach to
      management; and the outcome were documented for each patient. A PubMed literature
      search was also conducted, focusing on inflammatory exacerbations induced by
      griseofulvin, ketoconazole, itraconazole, fluconazole, and terbinafine. The
      patients were four farmers and one veterinarian (all male). All primary lesions
      were inflammatory dermatophytoses, including one kerion. Inflammatory
      exacerbation of the skin lesions started 12-24 hours after the intake of oral
      antifungals. Mild systemic changes, including slight fever and malaise, occurred
      in two cases. Itraconazole 400 mg/day was implicated as the causative agent in
      four cases and terbinafine 250 mg/day in one case. Mycologic cultures grew
      Trichophytonverrucosum in four cases. Antifungal treatment was discontinued in
      all patients. Oral and topical corticosteroids were administered to the two
      patients with systemic changes; the other three patients were treated with
      topical corticosteroids only. Two days after the onset of corticosteroids, lower
      doses of itraconazole (100 mg/day) and terbinafine (125 mg/day) were
      reintroduced. All lesions healed after 4-5 weeks. The PubMed search did not
      identify any articles that described inflammatory exacerbations of dermatomycoses
      induced by oral antifungals. Inflammatory flare-up of dermatomycoses is a rare
      but potentially severe cutaneous complication of oral antifungal use.
      Occupational contact with animals, inflammatory dermatomycoses, and zoophilic
      fungi represent common features in these patients. Although evidence-based data
      are not available, clinical experience shows that, in addition to antifungal
      therapy, topical and/or systemic corticosteroids are helpful to reduce the
      inflammatory reactions. The cases described in this article represent the first
      published report of oral antifungal-exacerbated inflammatory flare-up reactions
      of dermatomycosis in patients taking itraconazole or terbinafine.

PMID- 17007546
TI  - Enlarging tumor on the anterior scalp.

PMID- 17007545
TI  - A case report and discussion of cetuximab-induced folliculitis.
AB  - Use of human epidermal growth factor receptor inhibitors by oncologists has led
      to the occurrence of an acne-like eruption that is technically a folliculitis.
      Misidentification of the rash often leads to unfruitful treatment attempts as its
      morphologic features do not correlate well with its histologic findings. We
      describe a case history, diagnosis, and management of a man undergoing treatment
      with cetuximab for colorectal carcinoma who experienced the characteristic
      follicular eruption. Our patient responded well to daily moisturizers and 1%
      clindamycin gel and experienced near complete resolution of the rash. The
      evolving research and understanding of this unique entity are also discussed.

PMID- 17007548
TI  - Fractionated X-radiation treatment can elicit an inducible-like radioprotective
      response that is not dependent on the intrinsic cellular X-radiation
      resistance/sensitivity.
AB  - Inducible responses are well documented to play a role in the radiation response
      of cells. However, it is not known whether clinically relevant fractionated X
      radiation treatment could elicit an inducible-like radioprotective response and
      whether there is a direct correlation between the inducible radiation response
      phenomenon and the intrinsic radiation response of the cell. Therefore, the
      purpose of this study was to determine whether closely related human colorectal
      tumor (HCT116) clones treated with fractionated X rays could elicit an inducible
      like radiation response to a subsequent acute (i.e. single) X-ray challenge, and
      whether the magnitude of the inducible-like response correlates with the
      intrinsic X-ray resistance of the responding clones. After fractionated X
      irradiation, only the radiosensitive clone showed enhanced clonogenic survival
      with a subsequent acute X-ray exposure. Cell cycle changes or the selection of
      subclones with increased intrinsic radiation resistance induced by the
      fractionated X rays were excluded as the basis of this enhanced tolerance,
      suggesting the presence of an inducible-like radioprotective response. Using the
      comet assay, we found similar amounts of intrinsic DNA damage among the clones
      after acute X irradiation. Our findings demonstrate that fractionated X-ray
      treatment can elicit an inducible-like radioprotective response and represent the
      first evidence that this response is independent of the intrinsic radiation
      resistance/sensitivity of the responding cells.

PMID- 17007547
TI  - Cidofovir administered with radiation displays an antiangiogenic effect mediated
      by E6 inhibition and subsequent TP53-dependent VEGF repression in HPV18+ cell
      lines.
AB  - Therapeutic administration of the antiviral agent cidofovir with radiation
      markedly enhanced the antitumor effect of ionizing radiation in cells of two
      HPV18+ human cervical carcinoma cell lines. Although this potent radiosensitizing
      effect was associated with repression of the viral oncoproteins E6/ E7 and
      restoration of TP53 as shown previously, additional mechanisms may be involved.
      In the present study, we investigated the antiangiogenic effect of the
      combination of cidofovir and radiation in cells of two HPV18+ cervical cancer
      cell lines, HeLa and ME180, and assessed the molecular mechanisms associated with
      the antiangiogenic effect observed. Cells were exposed to cidofovir (10
      microg/ml) and irradiated (1-9 Gy). The angiogenic response was studied in vitro
      by a matrigel invasion assay. Modulations of E6, TP53 and VEGF mRNA and protein
      levels were studied by real-time RT-PCR, Western blot analysis and ELISA,
      respectively. Then a double RNA interference approach was used to analyze the
      connection between E6/TP53 and VEGF. The combination of cidofovir and radiation
      had a potent antiangiogenic effect. It induced E6 inhibition, restoration of
      TP53, and reduction of the proangiogenic phenotype of HPV18+ cells associated
      with VEGF inhibition. A siRNA strategy showed an anti-VEGF action of the
      combination mediated directly by E6 inhibition and TP53 restoration, since E6
      siRNA inhibited VEGF whereas co-transfection with E6 and TP53 siRNA abrogated the
      anti-VEGF effect. This study showed that the combination of cidofovir with
      ionizing radiation has an antiangiogenic effect associated with VEGF inhibition
      subsequent to E6 inhibition and TP53 restoration.

PMID- 17007549
TI  - Distinct mechanisms of nonhomologous end joining in the repair of site-directed
      chromosomal breaks with noncomplementary and complementary ends.
AB  - DNA double-strand breaks (DSBs) are considered the most important type of DNA
      damage inflicted by ionizing radiation. The molecular mechanisms of DSB repair by
      nonhomologous end joining (NHEJ) have not been well studied in live mammalian
      cells, due in part to the lack of suitable chromosomal repair assays. We
      previously introduced a novel plasmid-based assay to monitor NHEJ of site
      directed chromosomal I-SceI breaks. In the current study, we expanded the
      analysis of chromosomal NHEJ products in murine fibroblasts to focus on the error
      prone rejoining of DSBs with noncomplementary ends, which may serve as a model
      for radiation damage repair. We found that noncomplementary ends were efficiently
      repaired using microhomologies of 1-2 nucleotides (nt) present in the single
      stranded overhangs, thereby keeping repair-associated end degradation to a
      minimum (2-3 nt). Microhomology-mediated end joining was disrupted by Wortmannin,
      a known inhibitor of DNA-PKcs. However, Wortmannin did not significantly impair
      the proficiency of end joining. In contrast to noncomplementary ends, the
      rejoining of cohesive ends showed only a minor dependence on microhomologies but
      produced fivefold larger deletions than the repair of noncomplementary ends.
      Together, these data suggest the presence of several distinct NHEJ mechanisms in
      live cells, which are characterized by the degree of sequence deletion and
      microhomology use. Our NHEJ assay should prove a useful system to further
      elucidate the genetic determinants and molecular mechanisms of site-directed DSBs
      in living cells.

PMID- 17007550
TI  - Induction of micronuclei in human fibroblasts across the Bragg curve of energetic
      heavy ions.
AB  - The space environment consists of a varying field of radiation particles
      including high-energy ions, with spacecraft shielding material providing the
      major protection to astronauts from harmful exposure. Unlike low-LEpsilonTau
      gamma or X rays, the presence of shielding does not always reduce the radiation
      risks for energetic charged-particle exposure. The dose delivered by the charged
      particle increases sharply as the particle approaches the end of its range, a
      position known as the Bragg peak. However, the Bragg curve does not necessarily
      represent the biological damage along the particle path since biological effects
      are influenced by the track structures of both primary and secondary particles.
      Therefore, the "biological Bragg curve" is dependent on the energy and the type
      of the primary particle and may vary for different biological end points. Here we
      report measurements of the biological response across the Bragg curve in human
      fibroblasts exposed to energetic silicon and iron ions in vitro at two different
      energies, 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response
      curve generated for micronuclei per binucleated cell across the Bragg curve did
      not reveal an increased yield of micronuclei at the location of the Bragg peak.
      However, the ratio of mono- to binucleated cells, which indicates inhibition of
      cell progression, increased at the Bragg peak location. These results confirm the
      hypothesis that severely damaged cells at the Bragg peak are more likely to go
      through reproductive death and not be evaluated for micronuclei.

PMID- 17007551
TI  - Microdosimetric measurements and estimation of human cell survival for heavy-ion
      beams.
AB  - The microdosimetric spectra for high-energy beams of photons and proton, helium,
      carbon, neon, silicon and iron ions (LET = 0.5-880 keV/microm) were measured with
      a spherical-walled tissue-equivalent proportional counter at various depths in a
      plastic phantom. Survival curves for human tumor cells were also obtained under
      the same conditions. Then the survival curves were compared with those estimated
      by a microdosimetric model based on the spectra and the biological parameters for
      each cell line. The estimated alpha terms of the liner-quadratic model with a
      fixed beta value reproduced the experimental results for cell irradiation for ion
      beams with LETs of less than 450 keV/microm, except in the region near the distal
      peak.

PMID- 17007552
TI  - The release of bystander factor(s) from tissue explant cultures of rainbow trout
      (Onchorhynchus mykiss) after exposure to gamma radiation.
AB  - The bystander response has been documented in cell lines and cell cultures
      derived from aquatic species over the past several years. However, little work
      has been undertaken to identify a similar bystander response in tissue explant
      cultures from fish. In this study, indirect effects of ionizing gamma radiation
      on tissue explant cultures of fish were investigated. Tissue explants in culture
      were exposed to 0.5 Gy and 5 Gy gamma radiation from a 60Co teletherapy unit. A
      bystander response in Epithelioma papulosum cyprini (EPC) cells exposed to gamma
      irradiated tissue conditioned medium from rainbow trout explants was
      investigated, and the effects on cell survival were quantified by the clonogenic
      survival assay. Dichlorofluorescein and rhodamine 123 fluorescent dyes were used
      to identify alterations in reactive oxygen species (ROS) and mitochondrial
      membrane potential (MMP), respectively. Results indicate a different response for
      the three tissue types investigated. Clonogenic assay results vary from a
      decrease in cell survival (gill) to no effect (skin) to a stimulatory effect
      (spleen). Results from fluorescence assays of ROS and MMP show similarities to
      clonogenic assay results. This study identifies a useful model for further
      studies relating to the bystander effect in aquatic organisms in vivo and ex
      vivo.

PMID- 17007553
TI  - Hydroxylation of 3-nitrotyrosine and its derivatives by gamma irradiation.
AB  - Radiation-induced hydroxylation of 3-nitrotyrosine (3-NY) and its derivatives in
      aqueous solution were investigated as a function of gamma-radiation dose.
      Irradiated 3-NY, 3-nitrotyrosine ethyl ester (3-NYE) and 3-NY containing peptide
      Gly-nitroTyr-Gly were separated and analyzed with reverse-phase HPLC and UV-Vis
      absorption spectroscopy. The structures of the hydroxylated products were
      confirmed by electrospray ionization mass spectrometry and (1)H-NMR spectrometry.
      The amounts of the hydroxylated products in irradiated 3-NY and Gly-nitroTyr-Gly
      solutions increased with increasing radiation dose. Tandem electrospray
      ionization mass spectrometry (ESI-Mass(2)) was performed to investigate the
      hydroxylation of peptide Gly-nitroTyr-Gly. These studies showed that the
      hydroxylation occurred at 3-NY residue. We also found that the identification of
      3-NY hydroxylation in peptide could be identified by ion scanning for the
      specific immonium ion at m/z 197.0.

PMID- 17007554
TI  - Association of ionizing radiation-induced foci of NBS1 with chromosomal
      instability and breast cancer susceptibility.
AB  - NBS1, a protein essential for DNA double-strand break repair, relocalizes into
      subnuclear structures upon induction of DNA damage by ionizing radiation, forming
      ionizing radiation-induced foci. We compared radiation-induced NBS1 foci in
      peripheral blood lymphocytes (PBLs) from 46 sporadic breast cancer patients and
      30 healthy cancer-free volunteers. The number of persistent radiation-induced
      NBS1 foci per nucleus at 24 h after irradiation for patients with invasive cancer
      was significantly higher than for normal healthy volunteers. The frequency of
      spontaneous chromosome aberration increased as the number of persistent radiation
      induced NBS1 foci increased, indicating that the number of persistent radiation
      induced NBS1 foci might be associated with chromosome instability. There was also
      an inverse correlation between the number of radiation-induced NBS1 foci and the
      activity of DNA-dependent protein kinase (DNA-PK), which plays an important role
      in the nonhomologous end-joining (NHEJ) pathway, another mechanism of DNA DSB
      repair, indicating a close interrelationship between homologous recombination
      (HR) and NHEJ in DNA DSB repair. In conclusion, the number of persistent
      radiation-induced NBS1 foci is associated with chromosomal instability and risk
      of sporadic breast cancer and hence might be used to select individuals for whom
      a detailed examination is necessary because of their increased susceptibility to
      breast cancer, although refinement of the techniques for technical simplicity and
      accuracy will be required for clinical use.

PMID- 17007555
TI  - CHK2-dependent phosphorylation of BRCA1 in hypoxia.
AB  - Hypoxia induces a diverse spectrum of changes in the expression and activity of
      numerous DNA repair factors within the tumor microenvironment. In particular, we
      and others have shown that hypoxia induces phosphorylation and activation of the
      checkpoint kinase, CHK2, in an ATM-dependent manner. One downstream target of
      CHK2, the BRCA1 protein, plays a critical role in both DNA repair and cell cycle
      checkpoint regulation in mammalian cells. Here we report that BRCA1 is
      specifically phosphorylated on Serine 988 in response to hypoxic stress, and
      phosphorylation at this site is dependent on CHK2 expression. These findings
      enhance our understanding of ATM-CHK2 pathway activation in hypoxia, and they
      identify a novel role for BRCA1 in the response to hypoxic stress.

PMID- 17007558
TI  - Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation
      dose response and its modifiers.
AB  - Radiation exposure at a young age is a strong risk factor for thyroid cancer. We
      conducted a nested case-control study of 69 thyroid cancer cases and 265 controls
      from a cohort of 14,054 childhood cancer survivors to evaluate the shape of the
      radiation dose-response relationship, in particular at high doses, and to assess
      modification of the radiation effects by patient and treatment characteristics.
      We considered several types of statistical models to estimate the excess relative
      risk (ERR), mainly guided by radiobiological models. A two-parameter model with a
      term linear in dose and a negative exponential in dose squared provided the best
      parsimonious description with an ERR of 1.3 per gray (95% confidence interval 0.4
      4.1) at doses below 6 Gy and a relative decrease in ERR of 0.2% per unit dose
      squared with increasing dose, that is, decreases in the ERR/Gy of 53% at 20 Gy
      and 95% at 40 Gy. Further analyses using spline models suggested that the
      significant nonlinearity at high doses was characterized most appropriately as a
      true downturn rather than a flattening of the dose-response curve. We found no
      statistically significant modification of the dose-response relationship by
      patient characteristics; however, the linear parameter (i.e., the ERR/ Gy at
      doses less than 6 Gy) did decrease consistently and linearly with increasing age
      at childhood cancer diagnosis, from 4.45 for 0-1-year-olds to 0.48 for 15-20-year
      olds. In summary, we applied models derived from radiobiology to describe the
      radiation dose-response curve for thyroid cancer in an epidemiological study and
      found convincing evidence for a downturn in risk at high doses.

PMID- 17007559
TI  - Efficient photoinduced DNA damage by coralyne.
AB  - The photoinduced DNA damage by the berberine derivative coralyne is presented.
      The irradiation of coralyne in the presence of plasmid DNA namely, pBR322, leads
      to remarkably fast DNA damage by single-strand cleavage, as determined by agarose
      gel electrophoresis. Even upon exposure to sunlight, almost all of the
      supercoiled plasmid is converted to the open circular form in less than a minute
      [c(pBR322) = 3.5 x 10(-9) M; c(coralyne) = 4.3 x 10(-5) M]. The efficiency of the
      DNA strand cleavage is not decreased in the presence of radical-trapping reagents
      such as tert-butanol or DMSO. Moreover, the extent of the DNA damage is the same
      under aerobic conditions and at reduced oxygen concentration. Thus, the formation
      of reactive intermediates such as hydroxyl radicals or singlet oxygen is
      excluded. These results show that the exposure of coralyne and derivatives
      thereof to light, even with moderate light intensity, needs to be avoided during
      experiments in which their biological activity is assessed by plasmid unwinding
      assays.

PMID- 17007560
TI  - Combination of surgical resection and photodynamic therapy of 9L gliosarcoma in
      the nude rat.
AB  - The objective of the present study was to investigate the treatment of 9L
      gliosarcoma brain tumor in the rat with the combination of surgical resection and
      photodynamic therapy (PDT). Nude rats with intracranial 7-day-old 9L gliomas were
      randomly subjected to no treatment, PDT alone (Photofrin: 2 mg kg(-1), optical:
      80 J cm(-2)), surgical resection alone or resection combined with 2 mg kg(-1)
      Photofrin-mediated PDT at an optical dose of 80 J cm(-2). All animals were
      sacrificed 14 days after tumor implantation. Hematoxylin-and-eosin and
      immunohistochemical stainings were performed to assess the tumor volume and the
      expression of vascular endothelial growth factor (VEGF) in the brain adjacent to
      the tumor (BAT) as well as the tumor cell apoptosis and proliferation. Our data
      show that both surgical resection alone and PDT alone significantly decreased
      tumor volume, but furthermore, surgical resection combined with PDT significantly
      reduced the tumor volume and reduced local tumor infiltration compared to either
      surgical resection or PDT treatment alone. PDT treatment with or without
      resection increased tumor apoptosis, but resection alone did not alter the tumor
      cell apoptosis compared with a nontreatment control group. Both surgical
      resection alone and PDT alone induced a significant increase in VEGF expression
      in the BAT; however intraoperative PDT did not further increase VEGF expression,
      compared with surgery alone or PDT alone. No significant differences were found
      in tumor cell proliferation as indicated by Ki67 immunoreactivity among the four
      groups. Our results suggest that PDT enhances the efficacy of surgical resection
      in the management of malignant gliomas without increasing VEGF expression in the
      BAT.

PMID- 17007561
TI  - The surface oxidation potential of melanosomes measured by free electron laser
      photoelectron emission microscopy.
AB  - A technique for measuring the photoionization spectrum and the photoelectron
      emission threshold of a microscopic structured material is presented. The
      theoretical underpinning of the experiment and the accuracy of the measurements
      are discussed. The technique is applied to titanium silicide nanostructures and
      melanosomes isolated from human hair, human and bovine retinal pigment epithelium
      cells, and the ink sac of Sepia officinalis. A common photothreshold of 4.5 +/-
      0.2 eV is found for this set of melanosomes and is attributed to the
      photoionization of the eumelanin pigment. The relationship between the
      photoionization threshold and the electrochemical potential referenced to the
      normal hydrogen electrode is used to quantify the surface oxidation potential of
      the melanosome. The developed technique is used to examine the effect of iron
      chelation on the surface oxidation potential of Sepia melanosomes. The surface
      oxidation potential is insensitive to bound Fe(III) up to saturation, suggesting
      that the metal is bound to the interior of the granule. This result is discussed
      in relation to the age-dependent accumulation of iron in human melanosomes in
      both the eye and brain.

PMID- 17007562
TI  - Effect of UVC-induced damage to DNA on the intercalation of thiazole orange: a
      convenient reporter for DNA damage.
AB  - We report a novel method of identifying damage to DNA leading to the loss of
      intercalation sites. Thiazole orange (TO), an intercalating cyanine dye,
      fluoresces strongly when intercalated in DNA, but not free in solution. Upon UVC
      induced damage to DNA, the change in TO fluorescence is greater than the change
      in any of the other spectral or biochemical indicators (absorbance, circular
      dichroism and agarose gel electrophoresis), thus providing a fast screening
      method to identify damage to DNA. The method is geared toward high levels of
      damage, such as those that may result during radiation treatment of food
      products.

PMID- 17007563
TI  - Photosensitizing activity of advanced glycation endproducts on tryptophan,
      glucose 6-phosphate dehydrogenase, human serum albumin and ascorbic acid
      evaluated at low oxygen pressure.
AB  - A comparative study of the photosensitizing activity of advanced glycation
      endproducts (AGEs) prepared by incubating glucose (Glc), threose (Threo) and
      ascorbate (AH-) in the presence of lysine (Lys) was performed. Photochemical
      activity was evaluated under low oxygen pressure with the aim to simulate the
      conditions of the eye lens. AGE-sensitized tryptophan and AH- photodecomposition
      and glucose 6-phosphate dehydrogenase inactivation were studied. In all systems,
      glucose-derived AGEs showed the highest photosensitizing efficiency, followed by
      ascorbate and threose. The presence of different sensitizers in glycation
      products mixtures was investigated. For this purpose, Trp decomposition quantum
      yields were determined at 344 and 367 nm. The values obtained at 344 nm are
      between three and six times higher than those observed at 367 nm, confirming the
      presence of at least two compounds with different photosensitizing activities in
      the mixtures. The chemiluminescence associated with the AGE-mediated oxidation of
      free Trp and Trp residues in human serum albumin was also studied, and a good
      correlation between the emission of light and the extent of Trp decomposition was
      found. In conclusion, it is demonstrated that glucose derived AGEs, which can be
      formed in vivo in the eye lens of diabetic patients and are accumulated in
      elderly lenses, have a higher photosensitizing efficiency, at low oxygen
      pressure, than those arising from ascorbate and threose. This high efficiency is
      especially significant when proteins are employed as photochemical targets,
      indicating that protein-sensitizer interaction and the local environment around
      the sensitizers play an important role.

PMID- 17007564
TI  - Medium effects on zwitterionic-biradicaloid intermediates from two phenyl-alpha
      oxoamides. Irradiations in fluid and solid protic media, neat solid phases, and
      the solid, smectic and isotropic phases of a completely saturated phosphonium
      salt at different temperatures.
AB  - The photochemical processes of two N,N-dialkyl phenyl-alpha-oxoamides, N,N
      diisopropyl phenyl-alpha-oxoamide (1) and N,N-dibenzyl phenyl-alpha-oxoamide (2),
      are investigated at different temperatures in methanol and ethylene glycol (to
      probe the influences of H-bonding and viscosity), in the solid phase of D
      sorbitol at room temperature (to compare with the results in the liquid alcohols
      and to assess the influence of a poorly organized "stiff" environment), in the
      neat solid phase (to probe the influence of well-ordered, "stiff" matrices), and
      in the solid, smectic A2 and isotropic phases of methyl-tris
      tetradecylphosphonium tetrafluoroborate (1P14BF4) (to assess the ability of the
      intermediates to respond to subtle changes in the order and polarity of their
      local environments). From differences between the activation parameters for
      product pathways from irradiations in methanol and in 1P14BF4, we conclude that
      the zwitterionic pre-product intermediate from 1 is much more sensitive to the
      polarity, viscosity and order of its local environment than is the isomeric pre
      product biradicaloid intermediate or either of the pre-product intermediates from
      2. A very sensitive balance among the medium parameters, as well as internal
      steric and electronic factors of 1 and 2, controls the reactive pathways of the
      photochemically generated intermediates.

PMID- 17007565
TI  - Synthetic intron improves transduction efficiency of trans-splicing adeno
      associated viral vectors.
AB  - Trans-splicing adeno-associated viral (AAV) vectors hold great promise in many
      gene therapy applications. We have shown that rational selection of the gene
      splitting site in a therapeutic target gene can lead to extremely efficient trans
      splicing vectors [Lai, Y., Yue, Y., Liu, M., Ghosh, A., Engelhardt, J.F.,
      Chamberlain, J.S., and Duan, D. (2005). Nat. Biotechnol. 23, 1435-1439]. Our
      original strategy requires the screening of endogenous introns that are capable
      of overcoming the mRNA accumulation barrier. To further develop transsplicing
      vectors, we have tested whether the use of a generic synthetic intron can bypass
      the labor-intensive intron-screening process. Two previously characterized
      exon/intron/exon junctions (60/60/61 and 63/63/64, respectively) in the 6 kb
      minidystrophin gene were used as templates to represent highly efficient
      (60/60/61) and relatively poor (63/63/64) gene-splitting sites. We compared RNA
      production from the reconstituted viral genome and transduction efficiency of the
      trans-splicing vectors in dystrophin-null mdx mouse skeletal muscle. Our results
      suggest that a synthetic intron can successfully overcome the mRNA accumulation
      barrier at the exon 63/64 junction. Furthermore, when the gene was split at the
      exon 63/64 junction, the synthetic intronbased vectors performed better than the
      endogenous intron-based vectors. When the gene was split at the exon 60/61
      junction, we observed only nominal improvement in mRNA production. Nevertheless,
      vectors based on the exon 60/61 junction remain the best set in transduction
      efficiency. Taken together, our results suggest that optimizing intron sequence
      may boost the transduction efficiency of trans-splicing AAV vectors.

PMID- 17007567
TI  - Adenylylcyclase gene transfer increases function of the failing heart.
AB  - A persistent question in cardiovascular gene transfer concerns whether an
      exogenously delivered gene can increase function of the failing heart. Here we
      test the hypothesis that intracoronary delivery of adenovirus encoding
      adenylylcyclase type VI (Ad.ACVI) in the setting of active heart failure will
      increase function of the failing heart. As a model of heart failure, we used
      transgenic mice with dilated and poorly functioning hearts resulting from cardiac
      directed expression of Galphaq.Galphaq mice with equivalent pretreatment
      impairment in left ventricular (LV) function (echocardiography) received 2.5x1010
      viral particles of Ad.ACVI or Ad.EGFP (enhanced green fluorescent protein), or
      saline, by indirect intracoronary delivery. Serial echocardiograms obtained
      before and 14 days after gene transfer showed that Ad.ACVI increased LV ejection
      fraction (p<0.01) and velocity of circumferential fiber shortening (p<0.03).
      Detailed measurements in isolated hearts showed that ACVI gene transfer increased
      LV positive dP/dt (p=0.02) and LV negative dP/dt (p=0.01). Gene transfer was
      confirmed by polymerase chain reaction. These data show that, in an animal model
      that mimics key aspects of clinical congestive heart failure, cardiac gene
      transfer of ACVI increases function of the failing heart.

PMID- 17007566
TI  - Synthetic messenger RNA as a tool for gene therapy.
AB  - Transfection of human cells with DNA in biomedical applications carries the risk
      of insertional mutagenesis. Transfection with mRNA avoids this problem; however,
      in vitro production of mRNA, based on preliminary DNA template cloning in special
      vectors, is a laborious and time-consuming procedure. We report an efficient
      vectorfree method of mRNA production from polymerase chain reaction-generated DNA
      templates. For all cell types tested mRNA was transfected more readily than DNA,
      and its expression was highly uniform in cell populations. Even cell types
      relatively resistant to transfection with DNA could express transfected mRNA
      well. The level of mRNA expression could be controlled over a wide range by
      changing the amount of input RNA. Cells could be efficiently and simultaneously
      loaded with several different transcripts. To test a potential clinical
      application of this method, we transfected human T lymphocytes with mRNA encoding
      a chimeric immune receptor directed against CD19, a surface antigen widely
      expressed in leukemia and lymphoma. The transfected mRNA conferred powerful
      cytotoxicity to T cells against CD19+ targets from the same donor. These results
      demonstrate that this method can be applied to generate autologous T lymphocytes
      directed toward malignant cells.

PMID- 17007568
TI  - Intravenous delivery of anti-RhoA small interfering RNA loaded in nanoparticles
      of chitosan in mice: safety and efficacy in xenografted aggressive breast cancer.
AB  - Overexpression of RhoA in cancer indicates a poor prognosis, because of increased
      tumor cell proliferation and invasion and tumor angiogenesis. We showed
      previously that anti-RhoA small interfering RNA (siRNA) inhibited aggressive
      breast cancer more effectively than conventional blockers of Rho-mediated
      signaling pathways. This study reports the efficacy and lack of toxicity of
      intravenously administered encapsulated anti-RhoA siRNA in chitosan-coated
      polyisohexylcyanoacrylate (PIHCA) nanoparticles in xenografted aggressive breast
      cancers (MDA-MB-231). The siRNA was administered every 3 days at a dose of 150 or
      1500 microg/kg body weight in nude mice. This treatment inhibited the growth of
      tumors by 90% in the 150-microg group and by even more in the 1500-microg group.
      Necrotic areas were observed in tumors from animals treated with anti-RhoA siRNA
      at 1500 microg/kg, resulting from angiogenesis inhibition. In addition, this
      therapy was found to be devoid of toxic effects, as evidenced by similarities
      between control and treated animals for the following parameters: body weight
      gain; biochemical markers of hepatic, renal, and pancreatic function; and
      macroscopic appearance of organs after 30 days of treatment. Because of its
      efficacy and the absence of toxicity, it is suggested that this strategy of anti
      RhoA siRNA holds significant promise for the treatment of aggressive cancers.

PMID- 17007586
TI  - Challenged by complexity: my twentieth century in immunology.
AB  - My research career has focused on complex experimental systems, principally virus
      induced infectious processes. I have always run my own experimental program and
      never had a major mentor, although I have had many great colleagues. After
      graduating from the School of Veterinary Science at the University of Queensland,
      Australia, I worked for nine years on diseases of domestic animals. During that
      interval I completed a part-time PhD at the University of Edinburgh while
      employed as an experimental neuropathologist. Returning to the John Curtin School
      of Medical Research in Canberra, I focused on cell-mediated immunity, started to
      work seriously with mice, and thus became both an immunologist and a basic
      medical scientist. It was there in 1973 that Rolf Zinkernagel and I discovered
      MHC I-restricted CD8(+) T cell recognition, a finding that, together with the
      "single T cell receptor/altered self" hypothesis that we developed to explain our
      results, led to the 1996 Nobel Prize for Physiology or Medicine. Part of my focus
      since then has been to communicate the societal value and power of science to the
      broader community. As my scientific life is not yet over, I confine the present
      historical account to the twentieth century.

PMID- 17007587
TI  - Preconditioning: the mitochondrial connection.
AB  - Over the past decade there has been considerable progress in elucidating the
      signaling pathways involved in cardioprotection. Considerable recent data suggest
      that many of these signaling pathways converge on the mitochondria, where such
      pathways alter the activity of key mitochondrial proteins, leading to reduced
      apoptosis and necrosis. Inhibition of the mitochondrial permeability transition
      pore is emerging as a central mechanism in cardioprotection. This review focuses
      on mechanisms by which cardioprotection alters mitochondrial proteins and
      channels that regulate cell death and survival.

PMID- 17007595
TI  - Responsivity to offspring's expression of emotion among childhood-onset depressed
      mothers.
AB  - This study examined responsivity of mothers with childhood-onset depression (COD)
      in relation to children's overt expression of positive and negative emotion. It
      was hypothesized that COD and control mothers would differ in contingent
      responsivity to their children's expression of both positivity and different
      types of negative emotionality. Using observations and maternal reports of their
      own emotional reactions, COD mothers were found to be less responsive to
      children's expression of distress. A Gender x Group interaction was also found
      with respect to observed maternal responsiveness to child positivity, such that
      COD mothers were more responsive to girls' than boys' expression of positivity.
      The results are discussed in reference to transactional models of early child
      psychopathology.

PMID- 17007596
TI  - Schools, parents, and youth violence: a multilevel, ecological analysis.
AB  - Using data from the National Longitudinal Study of Adolescent Health (Add
      Health), this study utilized an ecological approach to investigate the joint
      contribution of parents and schools on changes in violent behavior over time
      among a sample of 6,397 students (54% female) from 125 schools. This study
      examined the main and interactive effects of parent and school connectedness as
      buffers of violent behavior within a hierarchical linear model, focusing on both
      students and schools as the unit of analysis. Results show that students who feel
      more connected to their schools demonstrate reductions in violent behavior over
      time. On the school level, our findings suggest that school climate serves as a
      protective factor for student violent behavior. Finally, parent and school
      connectedness appear to work together to buffer adolescents from the effects of
      violence exposure on subsequent violent behavior.

PMID- 17007597
TI  - Symptoms of depression and anxiety in children: specificity of the hopelessness
      theory.
AB  - The common etiology hypothesis proposes that depression and anxiety commonly co
      occur because they share etiological factors. This study examined the specificity
      of the hopelessness theory in the development of depressive and anxious symptoms
      in children. Students in Grades 3 through 6 (N = 418, 47% boys) completed
      measures assessing inferential styles about causes, consequences, and the self,
      depressive symptoms, and anxious symptoms. Six weeks later, children completed
      measures of depressive symptoms, anxious symptoms, and hassles. All 3 inferential
      styles interacted with hassles to predict increases in depressive symptoms,
      although this relation only held for children with low levels of initial
      symptoms. Inferential styles about consequences and the self also predicted
      increases in anxious symptoms. Consistent with the common etiology hypothesis,
      after controlling for the association between depressive and anxious symptoms,
      the effects of inferential styles about consequences and the self persisted.

PMID- 17007598
TI  - Client similarities and differences in two childhood anxiety disorders research
      clinics.
AB  - Some evidence suggests that research and service clinics differ on treatment
      relevant dimensions, but no study has examined whether research clinics (RCs)
      themselves differ. We compared 2 samples of children and adolescents (ages 7 to
      17 years) with anxiety disorders treated in 2 different university-based child
      anxiety RCs, one in Philadelphia (n = 184) and one in Miami (n = 64), on child
      symptom and diagnostic measures, family characteristics (e.g., income), and level
      of maternal depression. The samples were not significantly different on any youth
      symptom and diagnostic measures except 1 (parent-reported diagnoses); further,
      the 2 samples were statistically equivalent on 3 of 6 youth symptom measures.
      Although the Miami sample had significantly more parent-reported diagnoses than
      the Philadelphia sample, the effect size was small (Cohen's d = .44).
      Statistically significant differences between the samples in ethnic background
      and family income were observed, though the former was not significant after
      controlling for population differences. Findings are discussed in terms of the
      implications of homogeneity of RCs for treatments tested there.

PMID- 17007599
TI  - Body dissatisfaction prospectively predicts depressive mood and low self-esteem
      in adolescent girls and boys.
AB  - This research examined whether body dissatisfaction prospectively predicted
      depressive mood and low self-esteem in adolescent girls and boys 5 years later.
      Participants were early-adolescent girls (n = 440, Time 1 M age = 12.7 years) and
      boys (n = 366, Time 1 M age = 12.8 years) and midadolescent girls (n = 946, Time
      1 M age = 15.8 years) and boys (n = 764, Time 1 M age = 15.9 years). After
      controlling for Time 1 of the relevant dependent variable, ethnicity,
      socioeconomic status, and body mass index, Time 1 body dissatisfaction was a
      unique predictor of Time 2 depressive mood and low self-esteem in early
      adolescent girls (depressive mood: F = 4.80, p < .05; self-esteem: F = 9.64, p <
      .01) and midadolescent boys (depressive mood: F = 12.27, p < .001; self-esteem: F
      = 9.38, p < .01) but not in early-adolescent boys or midadolescent girls. These
      findings are consistent with the hypothesis that body dissatisfaction is a risk
      factor for depressive mood and low self-esteem in both girls and boys but in
      different phases of adolescence.

PMID- 17007600
TI  - Efficacy of cognitive-behavioral interventions targeting personality risk factors
      for youth alcohol misuse.
AB  - Sensation seeking, anxiety sensitivity, and hopelessness are personality risk
      factors for alcohol use disorders, each associated with specific risky drinking
      motives in adolescents. We developed a set of interventions and manuals that were
      designed to intervene at the level of personality risk and associated maladaptive
      coping strategies, including alcohol misuse. Manuals contained psychoeducational
      information on the target personality risk factor and how it is associated with
      maladaptive coping, as well as exercises targeting maladaptive cognitions and
      behaviors specific to each personality type. We tested the efficacy of these
      novel interventions on reducing drinking behavior by randomly assigning 297
      Canadian high school students (56% girls, mean age 16, mean grade 11) to
      personality-targeted interventions (group format; 2 sessions) or to a no
      treatment control group. Intent-to-treat analyses indicated beneficial effects of
      the intervention and Intervention x Personality interactions on drinking rates,
      drinking quantity, binge drinking, and problem drinking symptoms at 4-month
      follow-up.

PMID- 17007601
TI  - Family stability as a protective factor against psychopathology for urban
      children receiving psychological services.
AB  - Family stability, defined as the consistency of family activities and routines,
      was examined in a sample of urban families (n = 70) with children (ages 7 to 16)
      receiving psychological services. Parent-reported family stability was associated
      with lower parent-reported children's internalizing behavior problems. Child
      reported family stability significantly attenuated the influence of parental
      depressive symptoms on parent-reported children's internalizing, externalizing,
      and total behavior problems, while controlling for the effect of children's age.
      Parental depressive symptoms were associated with problems in child adjustment
      only at the low level of family stability.

PMID- 17007602
TI  - Childhood ADHD predicts risky sexual behavior in young adulthood.
AB  - This study compared young adults (ages 18 to 26) with and without childhood
      attention deficit hyperactivity disorder (ADHD) on self-reported risky sexual
      behaviors. Participants were 175 men with childhood ADHD and 111 demographically
      similar men without ADHD in the Pittsburgh ADHD Longitudinal Study (PALS).
      Childhood ADHD predicted earlier initiation of sexual activity and intercourse,
      more sexual partners, more casual sex, and more partner pregnancies. Although
      childhood conduct problems did contribute significantly to risky sexual behaviors
      among participants with ADHD, there was also an independent contribution of ADHD,
      suggesting that the characteristic deficits of the disorder or other associated
      features may be useful childhood markers of later vulnerability.

PMID- 17007603
TI  - A factor analytic approach to distinguish pure and co-occurring dimensions of
      proactive and reactive aggression.
AB  - This study used a confirmatory factor model to distinguish pure and co-occurring
      dimensions of proactive and reactive aggression, and examined the relation
      between parenting variables and these dimensions of aggression in a sample of 100
      children (9 to 12 years of age; 69 boys). Confirmatory factor analysis (CFA)
      supported 3 dimensions of proactive and reactive aggression: pure proactive, pure
      reactive, and their co-occurrence. Parenting variables differentially related to
      the pure and co-occurring dimensions of aggression. Findings indicate that CFA
      provides a promising approach for conceptualizing aggression on a continuum and
      allows researchers to distinguish pure and co-occurring dimensions of proactive
      and reactive aggression.

PMID- 17007604
TI  - The inclusion of fathers in the empirical investigation of child psychopathology:
      an update.
AB  - This investigation provides an update on the inclusion of fathers in child
      psychopathology research. Articles published from January 1992 to January 2005
      that examined parental contributions to child psychological maladjustment were
      identified. Each article was coded for child age, parental race, how parent
      gender was analyzed, type of journal, and year of publication. Overall, results
      replicated previous reviews (Phares & Compas, 1992), suggesting that fathers
      continue to be neglected in child psychopathology research. Further analyses
      revealed (a) higher rates of paternal research involvement as child age
      increased, (b) studies with a predominantly Caucasian sample included separate
      analyses for mothers and fathers more frequently than those with predominantly
      African American samples, (c) paternal research inclusion was higher in clinical
      compared to developmental psychology journals, and (d) over the past 6 years,
      more research has included fathers as participants than from the previous 7-year
      period (1992-1998).

PMID- 17007605
TI  - Parental assessment of childhood social phobia: psychometric properties of the
      social phobia and anxiety inventory for children-parent report.
AB  - Validity and parent-child agreement of the Social Phobia and Anxiety Inventory
      for Children-Parent Report (SPAI-C-P) were examined in a racially diverse sample
      of 158 students in Grades 5 through 8 (87 girls; ages 10 to 14; M = 11.53) and
      their caregivers. Children completed the Social Phobia and Anxiety Inventory for
      Children (SPAI-C), and caregivers completed the SPAI-C-P and the Child Behavior
      Checklist (CBCL). The SPAI-C-P demonstrated good internal consistency and was
      significantly correlated with child self-reported social anxiety. Confirmatory
      factor analysis supported a 3-factor model over a 5-factor model, and concurrent
      validity was evidenced. Implications and directions for future research are
      discussed.

PMID- 17007609
TI  - Mutagenesis and crystallographic studies of the catalytic residues of the papain
      family protease bleomycin hydrolase: new insights into active-site structure.
AB  - Bleomycin hydrolase (BH) is a hexameric papain family cysteine protease which is
      involved in preparing peptides for antigen presentation and has been implicated
      in tumour cell resistance to bleomycin chemotherapy. Structures of active-site
      mutants of yeast BH yielded unexpected results. Replacement of the active-site
      asparagine with alanine, valine or leucine results in the destabilization of the
      histidine side chain, demonstrating unambiguously the role of the asparagine
      residue in correctly positioning the histidine for catalysis. Replacement of the
      histidine with alanine or leucine destabilizes the asparagine position,
      indicating a delicate arrangement of the active-site residues. In all of the
      mutants, the C-terminus of the protein, which lies in the active site, protrudes
      further into the active site. All mutants were compromised in their catalytic
      activity. The structures also revealed the importance of a tightly bound water
      molecule which stabilizes a loop near the active site and which is conserved
      throughout the papain family. It is displaced in a number of the mutants, causing
      destabilization of this loop and a nearby loop, resulting in a large movement of
      the active-site cysteine. The results imply that this water molecule plays a key
      structural role in this family of enzymes.

PMID- 17007611
TI  - Chronic administration of genistein improves endothelial dysfunction in
      spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin
      expression and NADPH oxidase activity.
AB  - The soya-derived phytoestrogen genistein has been suggested to be protective in
      cardiovascular diseases. In the present study, we have analysed whether chronic
      oral genistein might influence endothelial function in male SHRs (spontaneously
      hypertensive rats) via ERs (oestrogen receptors), changes in eNOS (endothelial NO
      synthase) activity and vascular O(2)(-) (superoxide) production. Rats (23-weeks
      old) were divided into the following groups: WKY (Wistar-Kyoto)-vehicle, SHR
      vehicle, WKY-genistein (10 mg.kg(-1) of body weight.day(-1)); SHR-genistein; SHR
      genistein-faslodex (ICI 182780; 2.5 mg.kg(-1) of body weight.day(-1)). Vascular
      expression of eNOS, caveolin-1 and calmodulin-1 were analysed by Western
      blotting, eNOS activity by conversion of [(3)H]arginine into L-[(3)H]citrulline
      and O(2)(-) production by chemoluminescence of lucigenin. In SHRs, after 5 weeks
      of treatment, genistein reduced systolic blood pressure and enhanced endothelium
      dependent aortic relaxation to acetylcholine, but had no effect on the
      vasodilator responses to sodium nitroprusside. Compared with WKY rats, SHRs had
      up-regulated eNOS and down-regulated caveolin-1 and calmodulin-1 expression,
      increased NADPH-induced O(2)(-) production, but reduced eNOS activity. Genistein
      increased aortic calmodulin-1 protein abundance and eNOS activity, and reduced
      NADPH-induced O(2)(-) production in SHRs. The pure ERalpha and ERbeta antagonist
      faslodex did not modify any of the changes induced by genistein in SHRs,
      suggesting that these effects are unrelated to ER stimulation. In conclusion,
      genistein reduced the elevated blood pressure and endothelial dysfunction in
      SHRs. This latter effect appears to be related to increased eNOS activity
      associated with increased calmodulin-1 expression and decreased O(2)(-)
      generation.

PMID- 17007610
TI  - Two metallocarboxypeptidases from the protozoan Trypanosoma cruzi belong to the
      M32 family, found so far only in prokaryotes.
AB  - MCPs (metallocarboxypeptidases) of the M32 family of peptidases have been
      identified in a number of prokaryotic organisms, and only a few of them have been
      characterized biochemically. Members of this family are absent from eukaryotic
      genomes, with the remarkable exception of those of trypanosomatids. The genome of
      the CL Brener clone of Trypanosoma cruzi, the causative agent of Chagas' disease,
      encodes two such MCPs, with 64% identity between them: TcMCP-1 and TcMCP-2. Both
      genes, which are present in a single copy per haploid genome, were expressed in
      Escherichia coli as catalytically active polyHis-tagged recombinant enzymes.
      Despite their identity, the purified TcMCPs displayed marked biochemical
      differences. TcMCP-1 acted optimally at pH 6.2 on FA {N-(3-[2-furyl]acryloyl)}
      Ala-Lys with a K(m) of 166 muM. Activity against benzyloxycarbonyl-Ala-Xaa
      substrates revealed a P1' preference for basic C-terminal residues. In contrast,
      TcMCP-2 preferred aromatic and aliphatic residues at this position. The K(m)
      value for FA-Phe-Phe at pH 7.6 was 24 muM. Therefore the specificities of both
      MCPs are complementary. Western blot analysis revealed a different pattern of
      expression for both enzymes: whereas TcMCP-1 is present in all life cycle stages
      of T. cruzi, TcMCP-2 is mainly expressed in the stages that occur in the
      invertebrate host. Indirect immunofluorescence experiments suggest that both
      proteins are localized in the parasite cytosol. Members of this family have been
      identified in other trypanosomatids, which so far are the only group of
      eukaryotes encoding M32 MCPs. This fact makes these enzymes an attractive
      potential target for drug development against these organisms.

PMID- 17007613
TI  - Template for surgical training in resource-poor countries.

PMID- 17007612
TI  - The Dbs PH domain contributes independently to membrane targeting and regulation
      of guanine nucleotide-exchange activity.
AB  - Dbl family GEFs (guanine nucleotide-exchange factors) for the Rho GTPases almost
      invariably contain a PH (pleckstrin homology) domain adjacent to their DH (Dbl
      homology) domain. The DH domain is responsible for GEF activity, and the PH
      domain plays a regulatory role that remains poorly understood. We demonstrated
      previously that Dbl family PH domains bind phosphoinositides with low affinity
      and cannot function as independent membrane targeting modules. In the present
      study, we show that dimerization of a Dbs (Dbl's big sister) DH/PH domain
      fragment is sufficient to drive it to the plasma membrane through a mechanism
      involving PH domain-phosphoinositide interactions. Thus, the Dbs PH domain could
      play a significant role in membrane targeting if it co-operates with other
      domains in the protein. We also show that mutations that prevent phosphoinositide
      binding by the Dbs PH domain significantly impair cellular GEF activity even in
      chimaeric proteins that are robustly membrane targeted by farnesylation or by the
      PH domain of phospholipase C-delta1. This finding argues that the Dbs PH domain
      plays a regulatory role that is independent of its ability to aid membrane
      targeting. Thus, we suggest that the PH domain plays dual roles, contributing
      independently to membrane localization of Dbs (as part of a multi-domain
      interaction) and allosteric regulation of the DH domain.

PMID- 17007614
TI  - Point of care testing of aspirin resistance in patients with vascular disease.
AB  - INTRODUCTION: The reported range in rates of aspirin resistance (5.5-60%) may
      reflect difficulties in studying platelet function and the variety of tests used.
      This study used a platelet function analyzer (PFA-100) to prospectively document
      aspirin resistance in a cohort of patients with arterial disease. METHODS:
      Patients with internal carotid artery (ICA) stenosis or intermittent claudication
      (IC) were recruited. Exclusion criteria were contraindications to aspirin,
      prescription of other medication with known antiplatelet effects or known
      platelet abnormalities. After prescription of 100 mg aspirin/day for 2 weeks an
      uncuffed venous blood sample was taken and analysed with the PFA-100. Aspirin
      resistance was defined as closure time (CT) less than the upper limit of normal
      (158 s collagen/epinephrine agonist; 118 s collagen/adenosine diphosphate (ADP)
      agonist). RESULTS: Thirty-three patients with IC and 12 patients with ICA
      stenosis were recruited (n = 45). Median (range) age was 74 years (49-85) and the
      male to female ratio was 1.5:1. The median (range) CT was >300 (85 to >300) s
      with collagen/epinephrine and 100 (52 to >300) s with collagen/ADP agonist.
      Twelve patients (27%) in the collagen/epinephrine group had normal CT despite
      treatment with 100 mg aspirin, indicating resistance. Of the 33 patients with
      collagen/epinephrine CT prolonged by aspirin, 10 patients also had prolonged
      collagen/ADP CT, suggesting excessive platelet inhibition. CONCLUSION: A
      significant proportion of patients taking aspirin do not show laboratory evidence
      of platelet inhibition and may not be protected from atherothrombotic events. The
      PFA-100 appears to be a useful tool to screen for both aspirin resistance and
      excessive aspirin mediated platelet inhibition.

PMID- 17007615
TI  - Durability of autogenous vein and polytetrafluoroethylene bypass grafts to the
      carotid arteries.
AB  - BACKGROUND: Bypass for extra-cranial arterial disease is infrequently carried
      out. We reviewed our experience to determine the outcome of carotid artery
      grafting using either an autogenous vein or polytetrafluoroethylene (PTFE).
      METHODS: Details of patients were recorded prospectively as part of a vascular
      surgical registry. Patients identified from the registry as having carotid artery
      bypass procedures were classified according to the type of conduit used.
      Comparison was made between patients with autogenous vein and PTFE grafts.
      RESULTS: Between 1978 and 2002, 24 patients (13 men and 11 women) mean age 60.0
      +/- 13.4 years (range, 20-81 years) underwent 28 bypass procedures (three were
      bilateral and one was a reoperation). Symptomatic carotid disease was the
      clinical indication in 20 of 28 procedures (71.4%). Pathological indications
      included advanced atherosclerosis of the carotid arteries (15), past radiotherapy
      (4), failed stenting (3), resection of carotid body tumour (2), trauma (1),
      reoperation on a failed graft (1), carotid aneurysm (1) and iatrogenic carotid
      occlusion (1). An autogenous vein was used in 16, PTFE in 11 and autogenous
      artery in 1 of the patients. Using the Kaplan-Meier method, the overall patient
      cumulative 5-year survival was 84% and cumulative 5-year stroke-free survival was
      93%. The combined perioperative stroke and mortality rate was 7.1%. Two patients
      had transient ischaemic attacks (7.1%), one had cranial nerve palsies (3.6%) and
      one required reoperation for bleeding (3.6%). Five-year cumulative graft primary
      patency using the Kaplan-Meier method was 74% for PTFE grafts and 92% for
      autogenous vein grafts (P = 0.37). CONCLUSION: Carotid artery bypass is a safe
      and a useful treatment option for complex extra-cranial arterial disease. Either
      PTFE or autogenous veins may be used as conduits.

PMID- 17007616
TI  - Are biochemical values predictive of adenoma's weight in primary
      hyperparathyroidism?
AB  - BACKGROUND: Preoperative laboratory findings may carry some predictive value
      about the size of the abnormal parathyroid tissue that needs to be removed in
      primary hyperparathyroidism. METHODS: In a retrospective study from 1988 to 2003,
      records of 71 patients with parathyroid adenoma were reviewed. The correlation
      between preoperative serum calcium, phosphate and parathyroid hormone (PTH) with
      adenoma's weight was analysed separately. RESULTS: There was a significant
      correlation between preoperative serum PTH and calcium with adenoma's weight (P <
      0.001 and P = 0.03, respectively). The correlation between preoperative serum
      phosphate and adenoma's weight was not significant (P = 0.1). CONCLUSION:
      Preoperative PTH level cannot be used as a definite guide to the parathyroid
      adenoma's weight. Large parathyroid adenomas seem to secrete less PTH per unit
      weight than small adenomas. Calcium and phosphate do not seem to be of much value
      in predicting adenoma's weight in primary hyperparathyroidism.

PMID- 17007617
TI  - Predicting functional capacity outcome 12 months after hospitalized injury.
AB  - BACKGROUND: There is a recognized need to move from mortality to morbidity
      outcome predictions following traumatic injury. However, there are few morbidity
      outcome prediction scoring methods and these fail to incorporate important
      comorbidities or cofactors. This study aims to develop and evaluate a method that
      includes such variables. METHODS: This was a consecutive case series registered
      in the Queensland Trauma Registry that consented to a prospective 12-month
      telephone conducted follow-up study. A multivariable statistical model was
      developed relating Trauma Registry data to trichotomized 12-month post-injury
      outcome (categories: no limitations, minor limitations and major limitations).
      Cross-validation techniques using successive single hold-out samples were then
      conducted to evaluate the model's predictive capabilities. RESULTS: In total, 619
      participated, with 337 (54%) experiencing no limitations, 101 (16%) experiencing
      minor limitations and 181 (29%) experiencing major limitations 12 months after
      injury. The final parsimonious multivariable statistical model included whether
      the injury was in the lower extremity body region, injury severity, age, length
      of hospital stay, pulse at admission and whether the participant was admitted to
      an intensive care unit. This model explained 21% of the variability in post
      injury outcome. Predictively, 64% of those with no limitations, 18% of those with
      minor limitations and 37% of those with major limitations were correctly
      identified. CONCLUSION: Although carefully developed, this statistical model
      lacks the predictive power necessary for its use as a basis of a useful
      prognostic tool. Further research is required to identify variables other than
      those routinely used in the Trauma Registry to develop a model with the necessary
      predictive utility.

PMID- 17007618
TI  - Early trauma management skills in Australian general practitioners.
AB  - BACKGROUND: General practitioners (GPs) have a role in the early management of
      major trauma in rural Australia. The Early Management of Severe Trauma (EMST)
      course fulfils their educational needs by providing skills for the systematic
      management of the seriously injured patient. However, with any skill there is a
      natural loss over time. This study surveyed GPs who have completed the EMST
      course to determine their confidence in trauma management. METHODS: A two-page
      survey was mailed in December 2004 to all GPs who had completed an EMST course
      from 1989 to 2004 and were currently residing in Western Australia. The survey
      consisted of background questions, open-ended questions regarding the EMST course
      and skills confidence ratings using visual analogue scales. The final sample size
      was 223. RESULTS: Response rate was 55%. GPs were least confident in carrying out
      diagnostic peritoneal lavage and cricothyroidotomy. They were most confident
      inserting i.v. cannulas and managing fluid replacement. Their confidence in some
      of these skills were related to the frequency of managing trauma patients but not
      to the interval since completing the EMST course. GPs found the systematic
      approach to trauma management and practical/procedural skills as the most
      relevant components of EMST. They felt that EMST could be improved with more
      accessible refresher courses and more practical/procedural skills. CONCLUSION:
      Most of these GPs were involved in rural hospital work where they may be required
      to manage seriously injured patients. They require regular refresher courses to
      maintain their confidence levels in treating seriously injured patients.

PMID- 17007619
TI  - Acute surgical admissions for abdominal pain in adults in Kumasi, Ghana.
AB  - BACKGROUND: Abdominal pain of less than a weeks' duration is the presenting
      complaint in one of every five patients admitted to the surgical Accidents and
      Emergency Ward of the Komfo Anokye Teaching Hospital in Kumasi. This study is a
      prospective one, to determine the cause of abdominal pain in a large number of
      patients. METHODS: A monthly audit of discharge summaries for all patients
      admitted with acute abdominal pain was prepared and transferred to a special
      study pro forma to provide data over the 84-month period from January 1998 to
      December 2004. RESULTS: There were 3114 patients, 2070 men and 1044 women. The
      ages ranged from 15 to 95 years. The seven most common causes of the admissions
      were acute appendicitis 698 (22.4%), typhoid ileal perforation (506) 16.2%, acute
      intestinal obstruction 391 (12.6%), gastroduodenal perforations 342 (11.0%), non
      specific abdominal pain 306 (9.8%), abdominal injures 260 (8.3%) and acute
      cholecystitis 102 (3.2%). There were 1976 (63.4%) emergency operations.
      Appendicectomy was a common operation that was carried out (638 cases or 32.3%).
      Two hundred and thirty patients (7.4%) died. Thirty-five patients died before and
      195 after operation. Of these 230 deaths, 110 (47.8%) reported to the hospital
      after three or more days of illness. Twenty-six per cent and 23.7% of
      postoperative deaths occurred after emergency colonic resections and closure of
      gastroduodenal perforations, respectively. CONCLUSION: Acute appendicitis,
      typhoid ileal perforation, acute intestinal obstruction and gastroduodenal
      perforations were the leading causes of acute admissions for abdominal pain to
      our hospital. Late presentation was associated with increased mortality.

PMID- 17007620
TI  - Lower extremity venous changes in pneumoperitoneum during laparoscopic surgery.
AB  - BACKGROUND: The effect of pneumoperitoneum on veins of the lower limbs related to
      the intra-abdominal working pressures during laparoscopic cholecystectomy has not
      been thoroughly investigated. We tested the hypothesis that working pressures do
      not affect the venous haemodynamics in the lower limbs. METHODS: The cross
      sectional area and peak flow rates of femoral and saphenous veins in the right
      groin were measured in 60 patients divided into two groups according to the intra
      abdominal working pressures (11 vs 14 mmHg). All measurements were carried out
      preoperatively and at predetermined periods during and after laparoscopic
      cholecystectomy by colour Doppler ultrasonography. One-way anova and chi(2) test
      were used for the analysis of demographic data. For the repeated measures, anova
      and Student's t-test were used for statistical analysis. The probabilities less
      than 0.05 were accepted as statistically significant. RESULTS: The cross
      sectional area of the veins increased, whereas the peak flow rate in veins
      decreased during pneumoperitoneum. Comparing the peak flow rate in the saphenous
      vein at the third intraoperative measurement, there is statistically significant
      difference between the two groups (P < 0.05). CONCLUSION: The degree of intra
      abdominal pressure affects the haemodynamics of the peripheral veins.
      Pneumoperitoneum during laparoscopy causes stasis in the peripheral veins. It is
      reasonable to use routine prophylaxis for deep vein thrombosis, in the light of
      these findings.

PMID- 17007621
TI  - Influence of training on the family.
AB  - BACKGROUND: There is currently a shortage of surgeons working in rural Australia.
      This may be due to partner dissatisfaction with rural placements during training.
      METHODS: A questionnaire encompassing logistic, financial and emotional aspects
      of peripheral placements was distributed to trainees and their partners. A
      similar questionnaire was also distributed to 25 rural surgical consultants.
      RESULTS: Seventy-four per cent of trainees were either married or in long-term
      relationships. A further 24% had children. The average number of residential
      moves per year of training was 0.74. Respondents reported difficulties that
      included accommodation suitability, general practitioner availability, financial
      burden and finding amenities such as school and creches. Many (66%) partners had
      experienced high levels of isolation or loneliness, whereas some reported the
      development of a stress-related disorder, depression or anxiety. Most respondents
      indicated that their partner would influence their decision to work in a given
      location. Furthermore, 20% of consultant surgeons had either moved town or had
      seriously considered moving town because of their spouse or children's
      dissatisfaction. CONCLUSION: Training in peripheral locations causes significant
      stress to the trainee and their families. These experiences dissuade trainees
      from working in rural locations as consultants.

PMID- 17007622
TI  - Management of popliteal artery aneurysms.
AB  - BACKGROUND: Popliteal artery aneurysms (PAA) are the most common peripheral
      aneurysm and are recognized as 'the silent killer of the leg circulation'. The
      timing and type of interventions used in their treatment is still controversial.
      This review examines the published data on the natural history, epidemiology,
      clinical presentation and management options available. The aim of this study is
      to try and reach a consensus with regards to the best management of PAA. METHOD:
      A systematic review of data in the English published works since 1980. RESULTS:
      The authors include 53 studies containing 2854 patients with 4291 PAA. Most
      published data involves retrospective studies and personal experience, with one
      multicentre study. No randomized controlled studies exist regarding the
      management of PAA. CONCLUSIONS: 1. Although most PAA are of atherosclerotic
      origin in old patients, trauma, infection and family history are the main causes
      in young patients. 2. Great vigilance is needed for diagnosis as only
      approximately five patients are seen each year by a major vascular centre. There
      is no place for screening programmes to detect PAA. 3. Approximately 45% of
      patients are asymptomatic at the time of initial diagnosis. Aortic aneurysms are
      found in 40% and bilateral PAA in 50% of patients. More than 95% of patients are
      men with a mean age of 65 years and 45% have hypertension. 4. Surgical
      reconstruction is recommended for all symptomatic and asymptomatic aneurysms
      larger than 2 cm. Five-year graft patency rates after surgical repair range from
      30 to 97%, with 5-year limb salvage ranging from 70 to 98%. Patient survival
      rates at 5 and 10 years are 75 and 46%, respectively. 5. If carried out
      carefully, intra-arterial thrombolysis can safely prepare patients presenting
      with acute ischaemia from occluded PAA, for surgical revascularization to restore
      distal run-off. 6. Endovascular repair of a PAA is a feasible option, although
      little evidence is yet available. 7. Lifelong, careful patient surveillance is
      essential to detect and treat new aneurysms at other sites.

PMID- 17007623
TI  - The conundrum of claudication.
AB  - Stable claudication has traditionally been treated conservatively by many
      clinicians as operative therapies involve considerable risk for a condition that
      is often slowly progressive and non-fatal. The relative safety of less invasive
      endovascular techniques brings potential survival benefits from the increased
      exercise tolerance that result. We aimed to revisit and clarify the aetiologies
      of intermittent claudication in a review of the rarer causes that can mimic
      atherosclerotic occlusive disease. An extensive search of Medline, Embase and the
      Cochrane databases was carried out to compile published work addressing the
      aetiology of claudication and specific non-atherosclerotic causes. The reference
      lists of these manuscripts were also searched for relevant articles. There are
      several vasculogenic and neurogenic causes for intermittent claudication, many of
      which are unrelated to atherosclerosis. Recognition of these rarer syndromes is
      essential when planning endovascular or operative management strategies.
      Consideration of non-atherosclerotic differential diagnoses is recommended when
      assessing the patient with intermittent claudication. This is particularly
      critical in the young patient whose pattern of symptoms and risk factors may not
      fit precisely with atherosclerosis.

PMID- 17007624
TI  - Extralaryngeal bifurcation of the recurrent laryngeal nerve: a common variation.
AB  - Extralaryngeal bifurcation and trifurcation of the recurrent laryngeal nerve
      (RLN) is not well described in anatomical texts. This significant anatomical
      variation is important because prevention of vocal cord paralysis requires
      preservation of all branches of the RLN. The aim of this study was to examine the
      prevalence of extralaryngeal bifurcation of the RLN seen during
      thyroid/parathyroid surgeries. All patients undergoing total thyroidectomy,
      hemithyroidectomy and parathyroidectomy (excluding all minimally invasive
      procedures) carried out by a single endocrine surgeon from November 2003 to
      December 2004 were included. Operative data obtained prospectively included the
      location of the nerve, number of branches and the distance in millimetres from
      the inferior border of the cricothyroid to the point of bifurcation. A total of
      213 (right = 114, left = 99) RLN in 137 patients were studied. Seventy-seven
      (36%) nerves bifurcated or trifurcated before entry into the larynx. Bifurcations
      were more common on the right (43%) than on the left (28%) (P = 0.05).
      Trifurcations were seen in eight nerves, seven on the right and one on the left
      (P = 0.05). Bilaterally branched RLN were observed in 14 (18%) of 77 patients
      undergoing a bilateral procedure. One non-RLN was identified on the right. The
      median distance from the cricothyroid to the point of division was 18 mm on the
      right and 13 mm on the left. Extralaryngeal division of the RLN is a common
      anatomical variant occurring more frequently on the right. Unseen branches of the
      RLN are at risk of injury during surgery. Therefore, great care is required
      following presumed identification of the RLN to ensure that there are no other
      unidentified branches.

PMID- 17007625
TI  - Anatomical study of the ankle with view to the anterior arthroscopic portals.
AB  - This article evaluates the risk of interference with the neurovascular structures
      in the four anterior ankle arthroscopic portals, described on each side of the
      extensor tendons: anteromedial, medial midline, anterocentral and anterolateral.
      Complications after ankle arthroscopies have been described in up to 17%, most
      being neurovascular. To quantify the neurovascular risks we dissected 68
      cadaveric feet and evaluated the correlations between tendons, vessels and
      nerves. The mean distance between tibialis anterior and extensor hallucis longus
      and between extensor hallucis longus and extensor digitorum longus is 4 mm, but
      in 10-20% these tendons are in apposition or are overlapped. The tibialis
      anterior vascular bundle was absent in 11.8%, was located between the tibialis
      anterior and the extensor hallucis longus in 3% and between the extensor hallucis
      longus and the extensor digitorum longus in 64.7%. A peroneal vascular bundle or
      branches of the tibialis anterior vascular bundle were located lateral to the
      extensor digitorum longus/peroneus tertius tendon in 88.2%. Transverse vascular
      branches were identified in 41.2% over the medial side of the joint line and in
      52.9% over the lateral side. The deep peroneal nerve was located between the
      extensor hallucis longus and the extensor digitorum longus tendons in 58.8%. The
      superficial peroneal nerve had branches located between the tibialis anterior and
      the extensor hallucis longus tendons in 2.9%, between the extensor hallucis
      longus and the extensor digitorum longus tendons in 23.5% and lateral to the
      extensor digitorum longus/peroneus tertius tendon in 32.4%. These results show
      that the anteromedial and medial midline portals are the safest. The
      anterolateral portal should be noted not only for the risks to the superficial
      peroneal nerve, but also to the peroneal vessels.

PMID- 17007626
TI  - Specialist surgical training in Papua New Guinea: the outcomes after 10 years.
AB  - Surgical training commenced in 1975, the year that Papua New Guinea (PNG) gained
      independence. The training involves a 4-year programme leading to a Master of
      Medicine (MMed), awarded by the University of Papua New Guinea. In the past 30
      years just over 50 general surgeons have graduated. There have also been 9
      graduates in the area of ear nose and throat, 10 in ophthalmology and 2 in oral
      surgery. The subspecialization of general surgeons began in 1994 with four
      trainees, two orthopaedic, one head and neck and one urological. The model used
      was to develop specialist skills over 2-3 years only qualified (MMed) general
      surgeons so that their ability to carry out general surgical procedures and work
      in a remote hospital was not lost. The different specialties required different
      balances of in-country and out-of-country training depending on the local ability
      to provide training in PNG. An important sponsor has been the PNG National
      Department of Health, which has funded the training posts by using existing
      general surgical positions and covering the loss of manpower while surgeons are
      training overseas, sometimes for up to 2 years. Medical education and tertiary
      health service projects, funded by Aus-Aid, have also contributed significantly
      to the teaching and training. These projects have provided visiting specialists
      to teach and hospital attachments for national surgeons to train in Australasia.
      Various individual surgeons and their specialist societies in Australasia have
      also provided invaluable support. Three surgeons have been recipients of the
      Rowan Nicks scholarship. Twelve surgeons have been awarded a specialist diploma
      and a further five are in training. The posting of national specialist surgeons
      to Port Moresby has resulted in all modules of the General surgery MMed programme
      being taught by Papua New Guineans, which would have been hard to imagine back in
      1993. The MMed is now a sustainable programme and can be provided without
      external support. National surgeons carry out a wide range of specialist
      procedures, formerly carried out only by visiting teams. They are also able to
      make outreach visits within PNG and specialist visits to neighbouring Pacific
      Island countries.

PMID- 17007627
TI  - Concepts of transtibial amputation: Burgess technique versus modified Bruckner
      procedure.
AB  - The technique of a long posterior myocutaneous flap described by Ernest M.
      Burgess in the late 1960s is one of the most frequent procedures for below-knee
      amputations worldwide. To account for some potential problems associated with
      this procedure in patients with occlusive arterial disease, Lutz Bruckner
      developed a modified amputation technique for transtibial amputation in the
      1980s. Although this new standardized procedure has been widely used in Germany,
      it is not well known outside central Europe, secondary to its lack of description
      in English published work. In this review article, we describe a comparison of
      the technical aspects of the Burgess procedure with the modified Bruckner
      technique for transtibial amputations. In addition, the charts of 69 consecutive
      patients with end-stage occlusive arterial disease undergoing below-knee
      amputation by either of the two standardized procedures (Burgess, n = 29;
      Bruckner, n = 40) were reviewed. The clinical results of the two procedures are
      reported and compared. Review of the German published work suggests that the two
      techniques for transtibial amputation in patients with occlusive arterial disease
      appear to have similar results. This is further supported by data from our own 10
      year experience with 69 patients undergoing below-knee amputation by either of
      the two standardized procedures. This suggests that the Bruckner technique is at
      least equivalent to the Burgess procedure with regard to the clinical outcome in
      patients with occlusive arterial disease. The potential advantages of the
      standardized modified Bruckner procedure compared with the 'classical' Burgess
      technique for transtibial amputation remain to be assessed in prospective
      multicentre trials.

PMID- 17007628
TI  - Reversed intestinal rotation: report of two cases and review of the published
      reports.

PMID- 17007629
TI  - Component separation in the repair of a giant inguinoscrotal hernia.

PMID- 17007630
TI  - Neurological deficit as a presentation of occult metastatic thyroid carcinoma.
AB  - Three cases of occult metastatic thyroid carcinoma presenting with neurological
      deficits are reviewed. In each case the patient's initial presentation was with
      symptoms of neurological deficiency secondary to a spinal cord compression. All
      patients received a combination of surgery, external beam radiotherapy and
      postoperative thyroxine treatment. Two of the three patients are alive and well,
      able to mobilize with minor neurological dysfunction. The diagnosis and
      management of the patients, as well as their outcomes are reviewed, with a
      discussion on further management issues alongside a review of the current
      published work.

PMID- 17007632
TI  - Beyond open access: open discourse, the next great equalizer.
AB  - The internet is expanding the realm of scientific publishing to include free and
      open public debate of published papers. Journals are beginning to support web
      posting of comments on their published articles and independent organizations are
      providing centralized web sites for posting comments about any published article.
      The trend promises to give one and all access to read and contribute to cutting
      edge scientific criticism and debate.

PMID- 17007633
TI  - Ubiquitin crosstalk connecting cellular processes.
AB  - The polypeptide ubiquitin is used in many processes as different as endocytosis,
      multivesicular body formation, and regulation of gene transcription. Conjugation
      of a single ubiquitin moiety is typically used in these processes. A polymer of
      ubiquitin moieties is required for tagging proteins for proteasomal degradation.
      Besides its role in protein degradation, ubiquitin is also engaged as mono- or
      polymer in intracellular signalling and DNA repair. Since free ubiquitin is
      present in limiting amounts in cells, changes in the demands for ubiquitin in any
      of these processes is likely to indirectly affect other ubiquitin modifications.
      For example, proteotoxic stress strongly increases poly-ubiquitylated proteins at
      the cost of mono-ubiquitylated histones resulting in chromatin remodelling and
      altered transcription. Here we discuss the interconnection between ubiquitin
      dependent processes and speculate on the functional significance of the ubiquitin
      equilibrium as a signalling route translating cellular stress into molecular
      responses.

PMID- 17007634
TI  - Migraine, fibromyalgia, and depression among people with IBS: a prevalence study.
AB  - BACKGROUND: Case descriptions suggest IBS patients are more likely to have other
      disorders, including migraine, fibromyalgia, and depression. We sought to examine
      the prevalence of these conditions in cohorts of people with and without IBS.
      METHODS: The source of data was a large U.S. health plan from January 1, 1996
      though June 30, 2002. We identified all people with a medical claim associated
      with an ICD-9 code for IBS. A non-IBS cohort was a random sample of people with
      an ICD-9 code for routine medical care. In the cohorts, we identified all claims
      for migraine, depression, and fibromyalgia. We estimated the prevalence odds
      ratios (PORs) of each of the three conditions using the Mantel-Haenszel method.
      We conducted quantitative sensitivity analyses to quantify the impact of residual
      confounding and in differential outcome identification. RESULTS: We identified
      97,593 people in the IBS cohort, and a random sample of 27,402 people to compose
      the non-IBS comparison cohort. With adjustment, there was a 60% higher odds in
      the IBS cohort of having any one of the three disorders relative to the
      comparison cohort (POR 1.6, 95% CI 1.5 - 1.7). There was a 40% higher odds of
      depression in the IBS cohort (POR 1.4, 95% CI 1.3 - 1.4). The PORs for
      fibromyalgia and migraine were similar (POR for fibromyalgia 1.8, 95% CI 1.7 -
      1.9; POR for migraine 1.6, 95% CI 1.4 - 1.7). Differential prevalence of an
      unmeasured confounder, or imperfect sensitivity or specificity of outcome
      detection would have impacted the observed results. CONCLUSION: People in the IBS
      cohort had a 40% to 80% higher prevalence odds of migraine, fibromyalgia, and
      depression.

PMID- 17007636
TI  - The automatic recognition and counting of cough.
AB  - BACKGROUND: Cough recordings have been undertaken for many years but the analysis
      of cough frequency and the temporal relation to trigger factors have proven
      problematic. Because cough is episodic, data collection over many hours is
      required, along with real-time aural analysis which is equally time-consuming. A
      method has been developed for the automatic recognition and counting of coughs in
      sound recordings. METHODS: The Hull Automatic Cough Counter (HACC) is a program
      developed for the analysis of digital audio recordings. HACC uses digital signal
      processing (DSP) to calculate characteristic spectral coefficients of sound
      events, which are then classified into cough and non-cough events by the use of a
      probabilistic neural network (PNN). Parameters such as the total number of coughs
      and cough frequency as a function of time can be calculated from the results of
      the audio processing. Thirty three smoking subjects, 20 male and 13 female aged
      between 20 and 54 with a chronic troublesome cough were studied in the hour after
      rising using audio recordings. RESULTS: Using the graphical user interface (GUI),
      counting the number of coughs identified by HACC in an hour long recording, took
      an average of 1 minute 35 seconds, a 97.5% reduction in counting time. HACC
      achieved a sensitivity of 80% and a specificity of 96%. Reproducibility of
      repeated HACC analysis is 100%. CONCLUSION: An automated system for the analysis
      of sound files containing coughs and other non-cough events has been developed,
      with a high robustness and good degree of accuracy towards the number of actual
      coughs in the audio recording.

PMID- 17007635
TI  - Analysis of latent tuberculosis and mycobacterium avium infection data using
      mixture models.
AB  - BACKGROUND: Estimation of the frequency of latent tuberculosis infection (LTBI)
      is difficult in areas with low tuberculosis infection rates and high exposure to
      non-tuberculous mycobacteria (NTM), including BCG vaccination. The objective was
      to assess LTBI and M avium infection and to estimate their probability based on
      skin tests responses in an infant population from a region with the
      aforementioned characteristics. METHODS: A population-based tuberculin skin test
      (TST) and sensitin (M avium) survey was conducted on seven years old infants in
      Biscay, a province from The Basque Country (Spain). 2268 schoolchildren received
      sensitin and 5277 TST. Participation rate was 89%. Commonly used estimation
      methods were compared with a method based on the fit of mixture models using the
      Expectation Maximization algorithm. Functions estimating the probabilities of
      LTBI and M avium infection given the observed skin tests responses were developed
      for vaccinated and unvaccinated children. RESULTS: LTBI prevalences varied widely
      according to the estimation method. The mixture model provided prevalences higher
      than expected although intermediates between those obtained by currently
      recommended approaches. Exposure to previous BCG vaccine produces an upward shift
      of an average of about 3 mm on the induration size to attain the same probability
      of infection. CONCLUSION: Our results confirm the commonplace exposure to NTM
      which effect should be taken into account when performing and assessing
      tuberculin surveys. The use of mixture analysis under the empirical Bayes
      framework allows to better estimate the probability of LTBI in settings with
      presence of other NTM and high BCG-vaccination coverage. An estimation of the
      average effect of BCG vaccination on TST induration is also provided. These
      models maximise information coming from classical tuberculin surveys and could be
      used together with the newly developed blood tests to improve survey's
      specificity and cost-effectiveness.

PMID- 17007637
TI  - Right pulmonary artery occlusion by an acute dissecting aneurysm of the ascending
      aorta.
AB  - We describe the case of a 76-year old female who presented with a Type A aortic
      dissection requiring repair with an interposition graft and aortic valve
      replacement. Post-operatively she had clinical features and computerised
      tomographic images suggestive of a pulmonary embolus and died 24 hours later. The
      extremely rare finding of intramural thrombus occluding the right pulmonary
      artery was seen at post mortem.

PMID- 17007638
TI  - CD97 neutralisation increases resistance to collagen-induced arthritis in mice.
AB  - Synovial tissue of rheumatoid arthritis (RA) patients is characterised by an
      influx and retention of CD97-positive inflammatory cells. The ligands of CD97,
      CD55, chondroitin sulfate B, and alpha5beta1 (very late antigen [VLA]-5) are
      expressed abundantly in the synovial tissue predominantly on fibroblast-like
      synoviocytes, endothelium, and extracellular matrix. Based upon this expression
      pattern, we hypothesise CD97 expression to result in accumulation of inflammatory
      cells in the synovial tissue of RA patients. To determine the therapeutic effect
      of blocking CD97 in an animal model of RA, collagen-induced arthritis was induced
      in a total of 124 DBA/J1 mice. Treatment was started on day 21 (early disease) or
      on day 35 (longstanding disease) with the blocking hamster anti-mouse CD97
      monoclonal antibody (mAb) 1B2, control hamster immunoglobulin, or NaCl, applied
      intraperitoneally three times a week. The paws were evaluated for clinical signs
      of arthritis and, in addition, examined by radiological and histological
      analysis. Mice receiving 0.5 mg CD97 mAb starting from day 21 had significantly
      less arthritis activity and hind paw swelling. Furthermore, joint damage and
      inflammation were reduced and granulocyte infiltration was decreased. When
      treatment was started on day 35, CD97 mAb treatment had similar effects, albeit
      less pronounced. The results support the notion that CD97 contributes to synovial
      inflammation and joint destruction in arthritis.

PMID- 17007639
TI  - Gender associated differences in determinants of quality of life in patients with
      COPD: a case series study.
AB  - BACKGROUND: The influence of gender on the expression of COPD has received
      limited attention. Quality of Life (QoL) has become an important outcome in COPD
      patients. The aim of our study was to explore factors contributing to gender
      differences in Quality of Life of COPD patients. METHODS: In 146 men and women
      with COPD from a pulmonary clinic we measured: Saint George's Respiratory
      Questionnaire (SGRQ), age, smoking history, PaO2, PaCO2, FEV1, FVC, IC/TLC, FRC,
      body mass index (BMI), 6 minute walk distance (6MWD), dyspnea (modified MRC),
      degree of comorbidity (Charlson index) and exacerbations in the previous year. We
      explored differences between genders using Mann-Whitney U-rank test. To
      investigate the main determinants of QoL, a multiple lineal regression analysis
      was performed using backward Wald's criteria, with those variables that
      significantly correlated with SGRQ total scores. RESULTS: Compared with men,
      women had worse scores in all domains of the SGRQ (total 38 vs 26, p = 0.01,
      symptoms 48 vs 39, p = 0.03, activity 53 vs 37, p = 0.02, impact 28 vs 15, p =
      0.01). SGRQ total scores correlated in men with: FEV1% (-0.378, p < 0.001),
      IC/TLC (-0.368, p = 0.002), PaO2 (-0.379, p = 0.001), PaCO2 (0.256, p = 0.05),
      6MWD (-0.327, p = 0.005), exacerbations (0.366, p = 0.001), Charlson index
      (0.380, p = 0.001) and MMRC (0.654, p < 0.001). In women, the scores correlated
      only with FEV1% (-0.293, p = 0.013) PaO2 (-0.315, p = 0.007), exacerbations
      (0.290, p = 0.013) and MMRC (0.628, p < 0.001). Regression analysis (B, 95% CI)
      showed that exercise capacity (0.05, 0.02 to 0.09), dyspnea (17.6, 13.4 to 21.8),
      IC/TLC (-51.1, -98.9 to -3.2) and comorbidity (1.7, 0.84 to 2.53) for men and
      dyspnea (9.7, 7.3 to 12.4) and oxygenation (-0.3, -0.6 to -0.01) for women
      manifested the highest independent associations with SGRQ scores. CONCLUSION: In
      moderate to severe COPD patients attending a pulmonary clinic, there are gender
      differences in health status scores. In turn, the clinical and physiological
      variables independently associated with those scores differed in men and women.
      Attention should be paid to the determinants of QoL scores in women with COPD.

PMID- 17007640
TI  - Consistency and accuracy of diagnostic cancer codes generated by automated
      registration: comparison with manual registration.
AB  - BACKGROUND: Automated procedures are increasingly used in cancer registration,
      and it is important that the data produced are systematically checked for
      consistency and accuracy. We evaluated an automated procedure for cancer
      registration adopted by the Lombardy Cancer Registry in 1997, comparing
      automatically-generated diagnostic codes with those produced manually over one
      year (1997). METHODS: The automatically generated cancer cases were produced by
      Open Registry algorithms. For manual registration, trained staff consulted
      clinical records, pathology reports and death certificates. The social security
      code, present and checked in both databases in all cases, was used to match the
      files in the automatic and manual databases. The cancer cases generated by the
      two methods were compared by manual revision. RESULTS: The automated procedure
      generated 5027 cases: 2959 (59%) were accepted automatically and 2068 (41%) were
      flagged for manual checking. Among the cases accepted automatically,
      discrepancies in data items (surname, first name, sex and date of birth)
      constituted 8.5% of cases, and discrepancies in the first three digits of the ICD
      9 code constituted 1.6%. Among flagged cases, cancers of female genital tract,
      hematopoietic system, metastatic and ill-defined sites, and oropharynx
      predominated. The usual reasons were use of specific vs. generic codes, presence
      of multiple primaries, and use of extranodal vs. nodal codes for lymphomas. The
      percentage of automatically accepted cases ranged from 83% for breast and thyroid
      cancers to 13% for metastatic and ill-defined cancer sites. CONCLUSION: Since 59%
      of cases were accepted automatically and contained relatively few, mostly trivial
      discrepancies, the automatic procedure is efficient for routine case generation
      effectively cutting the workload required for routine case checking by this
      amount. Among cases not accepted automatically, discrepancies were mainly due to
      variations in coding practice.

PMID- 17007641
TI  - Repeated successful surgical rescues of early and delayed multiple ruptures of
      ventricular septum, right ventricle and aneurysmal left ventricle following
      massive biventricular infarction.
AB  - A 58 year old man underwent 6 surgical interventions for various complications of
      massive biventricular myocardial infarction over a period of 2 years following
      acute occlusion of a possibly "hyperdominant" left anterior descending coronary
      artery. These included concomitant repair of apicoanterior post-infarction VSD
      and right ventricular free wall rupture, repeat repair of recurrent VSD following
      inferoposterior extension of VSD in the infarcted septum 5 weeks later, repair of
      delayed right ventricular free wall rupture 4 weeks subsequently, repair of a
      bleeding left ventricular aneurysm eroding through left chest wall 16 months
      thereafter, repair of right upper lobe lung tear causing massive anterior
      mediastinal haemorrhage, mimicking yet another cardiac rupture, 2 months later,
      followed, at the same admission, 2 weeks later, by sternal reconstruction for
      dehisced and infected sternum using pedicled myocutaneous latissimus dorsi flap.
      5 years after the latissimus myoplasty, the patient remains in NYHA class 1 and
      is leading a normal life.

PMID- 17007643
TI  - A novel electron paramagnetic resonance-based assay for prostaglandin H synthase
      1 activity.
AB  - BACKGROUND: Prostaglandin H2 synthase (PGHS) is the enzyme that catalyses the two
      stage conversion of arachidonic acid to prostaglandin H2 (PGH2) prior to
      formation of prostanoids that are important in inflammation. PGHS isozymes (-1
      and -2) are the target for nonsteroidal anti-inflammatory drugs (NSAIDs). Given
      the rekindled interest in specific anti-inflammatory PGHS inhibitors with reduced
      unwanted side effects, it is of paramount importance that there are reliable and
      efficient techniques to test new inhibitors. Here, we describe a novel in vitro
      electron paramagnetic resonance (EPR)-based assay for measuring the activity of
      PGHS-1. METHODS: We validated a novel in vitro PGHS-1 activity assay based on the
      oxidation of spin-trap agent, 1-hydroxy-3-carboxy-pyrrolidine (CPH) to 3-carboxy
      proxy (CP) under the action of the peroxidase element of PGHS-1. This
      quantifiable spin-adduct, CP, yields a characteristic 3-line electron
      paramagnetic (EPR) spectrum. RESULTS: The assay is simple, reproducible and
      facilitates rapid screening of inhibitors of PGHS-1. Aspirin (100 microM, 1 mM)
      caused significant inhibition of spin-adduct formation (72 +/- 11 and 100 +/- 16%
      inhibition of control respectively; P < 0.05). Indomethacin (100 microM) also
      abolished the signal (114 +/- 10% inhibition of control; P < 0.01). SA and the
      PGHS-2-selective inhibitor, NS398, failed to significantly inhibit spin-adduct
      generation (P > 0.05). CONCLUSION: We have demonstrated and validated a simple,
      reproducible, quick and specific assay for detecting PGHS-1 activity and
      inhibition. The EPR-based assay described represents a novel approach to
      measuring PGHS activity and provides a viable and competitive alternative to
      existing assays.

PMID- 17007642
TI  - Survey and analysis of microsatellites from transcript sequences in Phytophthora
      species: frequency, distribution, and potential as markers for the genus.
AB  - BACKGROUND: Members of the genus Phytophthora are notorious pathogens with world
      wide distribution. The most devastating species include P. infestans, P. ramorum
      and P. sojae. In order to develop molecular methods for routinely characterizing
      their populations and to gain a better insight into the organization and
      evolution of their genomes, we used an in silico approach to survey and compare
      simple sequence repeats (SSRs) in transcript sequences from these three species.
      We compared the occurrence, relative abundance, relative density and cross
      species transferability of the SSRs in these oomycetes. RESULTS: The number of
      SSRs in oomycetes transcribed sequences is low and long SSRs are rare. The in
      silico transferability of SSRs among the Phytophthora species was analyzed for
      all sets generated, and primers were selected on the basis of similarity as
      possible candidates for transferability to other Phytophthora species. Sequences
      encoding putative pathogenicity factors from all three Phytophthora species were
      also surveyed for presence of SSRs. However, no correlation between gene function
      and SSR abundance was observed. The SSR survey results, and the primer pairs
      designed for all SSRs from the three species, were deposited in a public
      database. CONCLUSION: In all cases the most common SSRs were trinucleotide repeat
      units with low repeat numbers. A proportion (7.5%) of primers could be
      transferred with 90% similarity between at least two species of Phytophthora.
      This information represents a valuable source of molecular markers for use in
      population genetics, genetic mapping and strain fingerprinting studies of
      oomycetes, and illustrates how genomic databases can be exploited to generate
      data-mining filters for SSRs before experimental validation.

PMID- 17007644
TI  - Identification and characterization of the heme-binding proteins SeShp and SeHtsA
      of Streptococcus equi subspecies equi.
AB  - BACKGROUND: Heme is a preferred iron source of bacterial pathogens. Streptococcus
      equi subspecies equi is a bacterial pathogen that causes strangles in horses.
      Whether S. equi has a heme acquisition transporter is unknown. RESULTS: An S.
      equi genome database was blasted with the heme binding proteins Shp and HtsA of
      Streptococcus pyogenes, and found that S. equi has the homologue of Shp
      (designated SeShp) and HtsA (designated SeHtsA). Tag-free recombinant SeShp and
      SeHtsA and 6xHis-tagged SeHtsA (SeHtsAHis) were prepared and characterized.
      Purified holoSeShp and holoSeHtsA bind Fe(II)-protoporphyrin IX (heme) and
      Fe(III)-protoporphyrin IX (hemin) in a 1:1 stoichiometry, respectively, and are
      designated hemoSeShp and hemiSeHtsA. HemiSeShp and hemiSeHtsAHis can be
      reconstituted from apoSeShp and apoSeHtsAHis and hemin. HemoSeShp is stable in
      air and can be oxidized to hemiSeShp by ferricyanide. HemiSeHtsA can be reduced
      into hemoSeHtsA, which autoxidizes readily. HemoSeShp rapidly transfers its heme
      to apoSeHtsAHis. In addition, hemoSeShp can also transfer its heme to apoHtsA,
      and hemoShp is able to donate heme to apoSeHtsAHis. CONCLUSION: The primary
      structures, optical properties, oxidative stability, and in vitro heme transfer
      reaction of SeShp and SeHtsA are very similar to those of S. pyogenes Shp and
      HtsA. The data suggest that the putative cell surface protein SeShp and
      lipoprotein SeHtsA are part of the machinery to acquire heme in S. equi. The
      results also imply that the structure, function, and functional mechanism of the
      heme acquisition machinery are conserved in S. equi and S. pyogenes.

PMID- 17007645
TI  - The impact of iron overload and its treatment on quality of life: results from a
      literature review.
AB  - BACKGROUND: To assess the literature for the impact of iron overload and infusion
      Iron Chelation Therapy (ICT) on patients' quality of life (QoL), and the
      availability of QoL instruments for patients undergoing infusion ICT. Also, to
      obtain patients' experiences of having iron overload and receiving infusion ICT,
      and experts' clinical opinions about the impact of treatment on patients' lives.
      METHODS: A search of studies published between 1966 and 2004 was conducted using
      Medline and the Health Economic Evaluation Database (HEED). Qualitative results
      from patient and expert interviews were analysed. Hand searching of relevant
      conference abstracts completed the search. RESULTS: Few studies measuring the
      impact of ICT with deferoxamine (DFO) on patients QoL were located (n = 15). QoL
      domains affected included: depression; fatigue; dyspnoea; physical functioning;
      psychological distress; decrease in QoL during hospitalization. One theme in all
      articles was that oral ICT should improve QoL. No iron overload or ICT-specific
      QoL instruments were located in the articles. Interviews revealed that the impact
      of ICT on patients with thalassemia, sickle cell disease, and myelodysplastic
      syndromes is high. CONCLUSION: A limited number of studies assessed the impact of
      ICT or iron overload on QoL. All literature suggested a need for easily
      administered, efficacious and well tolerated oral iron overload treatments, given
      the impact of current ICT on adherence. Poor adherence to ICT was documented to
      negatively impact survival. Further research is warranted to continue the
      qualitative and quantitative study of QoL using validated instruments in patients
      receiving ICT to further understanding the issues and improve patients QoL.

PMID- 17007646
TI  - The effects of moderate fatigue on dynamic balance control and attentional
      demands.
AB  - BACKGROUND: During daily activities, the active control of balance often is a
      task per se (for example, when standing in a moving bus). Other constraints like
      fatigue can add to the complexity of this balance task. In the present
      experiment, we examined how moderate fatigue induced by fast walking on a
      treadmill challenged dynamic balance control. We also examined if the attentional
      demands for performing the balance task varied with fatigue. METHODS: Subjects (n
      = 10) performed simultaneously a dynamic balance control task and a probe
      reaction time task (RT) (serving as an indicator of attentional demands) before
      and after three periods of moderate fatigue (fast walking on a treadmill). For
      the balance control task, the real-time displacement of the centre of pressure
      (CP) was provided on a monitor placed in front of the subject, at eye level.
      Subjects were asked to keep their CP within a target (moving box) moving upward
      and downward on the monitor. The tracking performance was measured (time spent
      outside the moving box) and the CP behavior analyzed (mean CP speed and mean
      frequency of the CP velocity). RESULTS: Moderate fatigue led to an immediate
      decrement of the performance on the balance control task; increase of the
      percentage of time spent outside the box and increase of the mean CP speed.
      Across the three fatigue periods, subjects improved their tracking performance
      and reduced their mean CP speed. This was achieved by increasing their frequency
      of actions; mean frequency of the CP velocity were higher for the fatigue periods
      than for the no fatigue periods. Fatigue also induced an increase in the
      attentional demands suggesting that more cognitive resources had to be allocated
      to the balance task with than without fatigue. CONCLUSION: Fatigue induced by
      fast walking had an initial negative impact on the control of balance.
      Nonetheless, subjects were able to compensate the effect of the moderate fatigue
      by increasing the frequency of actions. This adaptation, however, required that a
      greater proportion of the cognitive resources be allocated to the active control
      of the balance task.

PMID- 17007647
TI  - Endovascular control of haemorrhagic urological emergencies: an observational
      study.
AB  - BACKGROUND: Transarterial embolisation (TAE) is an effective method in control of
      haemorrhage irrespective of the nature of urological emergency. As the technique
      and technology have evolved, it is now possible to perform highly selective
      embolisation. The aim of this study was to critically appraise feasibility and
      efficacy of therapeutic TAE in control of haemorrhagic urological emergencies
      using selective and non-selective embolisation. Specifically, we aimed to assess
      the impact of timing of embolisation on the requirement of blood transfusion and
      long-term morphological and functional follow-up of embolised organs. METHODS:
      This is a single institutional observational study carried out between March 1992
      and March 2006. Records of all patients who underwent selective and non-selective
      angioembolisation to control bleeding in urological emergencies were reviewed.
      Data on success rate, periprocedural complications, timing of embolisation,
      requirement of blood transfusion and the long-term morphological and functional
      outcomes of embolised organs was recorded. RESULTS: Fourteen patients underwent
      endovascular control of bleeding as a result of trauma, iatrogenic injury and
      spontaneous perinephric haemorrhage during a period of 14 years. All these
      patients would have required emergency open surgery without the option of
      embolisation procedure. The mean time between the first presentation and
      embolisation was 22 hours (range 30 minutes to 60 hours). Mean pre-embolisation
      transfusion requirement was 6.8 units (range 0-22 units). None of the patients
      with successful embolisation required post-procedural blood transfusion.
      Permanent haemostasis was achieved in all but one patient, who required emergency
      nephrectomy. There were no serious procedure related post-embolisation
      complications. CONCLUSION: Endovascular control using transarterial
      angioembolisation is an effective method for managing haematuria or haemorrhage
      in urological emergencies. Wherever and whenever indicated, this option should be
      considered early in the management of these cases.

PMID- 17007648
TI  - Firing patterns of rat vestibulospinal neurons during quadrupedal standing on a
      pitching platform.
AB  - The neuronal activity of vestibulospinal neurons projecting to the lumbar
      enlargement was recorded in conscious rats standing with four limbs on a pitching
      platform. The neurons were classified into 3 groups: up-neurons firing maximally
      in the head-up phase (2/8), down-neurons with maximal firing in the head-down
      phase (2/8), and nonmodulated neurons (4/8). The 3 groups may play differential
      roles in stance control.

PMID- 17007649
TI  - Information leaflets in medical screening.

PMID- 17007650
TI  - Women's information needs about ductal carcinoma in situ before mammographic
      screening and after diagnosis: a qualitative study.
AB  - OBJECTIVES: To explore the attitudes of women with screen-detected ductal
      carcinoma in situ (DCIS) towards information provision for mammographic
      screening. SETTING: Respondents recruited throughout the UK during 2003-2004.
      METHODS: Qualitative study using semi-structured interviews. PARTICIPANTS: Ten
      women diagnosed with DCIS as a result of mammographic screening. RESULTS: None of
      the women with DCIS had heard of it before their diagnosis. Most would have liked
      more information about DCIS when invited for routine screening. Comprehensive
      information about the benefits and risks of mammographic screening, including the
      possibility of a DCIS diagnosis, would have enabled them to make a fully informed
      choice about attending for screening. CONCLUSION: DCIS is an inescapable outcome
      of mammographic screening and, until it is better understood, the screening
      industry needs to inform women about its existence and the lack of understanding
      of its natural history and management. Being alerted before screening to the
      possibility of a DCIS diagnosis and the uncertainty associated with it would
      better enable women to make fully informed decisions about whether to attend and
      could help to alleviate some of the distress women currently feel when diagnosed
      with DCIS.

PMID- 17007651
TI  - Interval breast cancers: prognostic features and survival by subtype and time
      since screening.
AB  - OBJECTIVES: To investigate the hypothesis that interval cancers arising soon
      after the previous screen and true interval cancers are biologically aggressive
      and have a relatively poor prognosis compared with other interval cancers, and to
      assess which prognostic features are relevant to interval cancers. METHODS:
      Analysis of prognostic pathological features (grade, lymph node stage, size,
      vascular invasion, oestrogen receptor [ER] status and histological type),
      radiological features (comedo/non-comedo calcification and spiculation) and
      survival for 538 invasive interval breast cancer cases by type and time since
      previous screen. RESULTS: Late interval cancers were less likely to be lymph node
      positive (13 versus 43%, P = 0.003). Type 1 interval cancers were more likely to
      be histological grade 3 than type 2 (minimal signs) and type 3 (false-negative)
      intervals (52 versus 35%, P = 0.05). Type 3 interval cancers were more likely to
      have lobular features than other intervals (47 versus 20%, P < 0.0001). There was
      no significant survival difference by interval cancer type (P = 0.64) or interval
      year (P = 0.83). At univariate analysis of all interval cancers, tumour size,
      grade, nodal stage, ER status, vascular invasion and comedo calcification were
      associated with survival. On multivariate analysis of prognostic features
      significant at univariate analysis, nodal stage (P value = 0.009), tumour size (P
      = 0.001), ER status (P < 0.0001) and vascular invasion (P < 0.0001) maintained
      independent significance. CONCLUSIONS: Our study shows that true intervals and
      interval cancers arising quickly after screening do not have a worse prognosis
      than other interval cancers, and that interval cancers have a unique set of
      prognostic features.

PMID- 17007652
TI  - The effect of screening programmes on the treatment of benign breast neoplasms:
      observations from current practice in Italy.
AB  - PURPOSE: In the Lazio region, Italy, mammographic screening programmes were
      gradually activated from 1999 to 2003, providing an opportunity to compare two
      unselected populations in the same time period: women who were contacted in
      writing, and those who had not been contacted. In this study, we compare the
      incidences of treatments for benign and malignant neoplasms in the two groups.
      METHODS: The target population was women aged 50-69 years. We linked all incident
      cases of surgery for benign and malignant breast neoplasms, from the Hospital
      Information System (1999-2003) to the Mammographic Screening Information System
      (1999-2001). We calculated incidence, adjusted for age and standardized breast
      cancer mortality ratio in each area of residence, for benign and malignant
      neoplasms surgery in non-yet-contacted and contacted woman. Incidence for
      contacted women was calculated for the two years following initial contact.
      RESULTS: The target population in Lazio is 681,000; 116,000 women were contacted
      during the study period and 3252 malignant and 1566 benign neoplasms were
      surgically treated. Annual incidence was, respectively, 2.0/1000 and 1.1/1000 for
      malignant and benign neoplasms in women not contacted, and, respectively,
      2.9/1000 and 1.1/1000 in the contacted population. Among the contacted group,
      annual incidence was 4.3/1000 and 1.5/1000 in compliant women, and 2.0/1000 and
      0.9/1000 in non-compliant women. About one-half of the surgeries for benign
      neoplasms in compliant women were treated against the recommendation of the
      screening programme. CONCLUSIONS: The implementation of the screening programme
      did not increase the incidence of treatment for benign neoplasms, and detected
      50% more malignant neoplasms.

PMID- 17007653
TI  - Red blood cell disorders in Rwandese neonates: screening for sickle cell disease
      and glucose-6-phosphate dehydrogenase deficiency.
AB  - OBJECTIVES: To determine the prevalence of haemoglobin (Hb) variants and glucose
      6-phosphate dehydrogenase (G6PD) deficiency in Rwanda. METHODS: During a two
      month period in 2005, 987 cord blood samples were obtained in two hospitals in
      Kigali and Butare, Rwanda. Screening for sickle cell disorders, other Hb
      disorders, G6PD deficiency and other rare erythroenzymopathy deficiencies was
      done using isoelectric focusing techniques and quantitative kinetic assays,
      respectively. RESULTS: The prevalence of Hb S trait was 2.7% and that of G6PD
      deficiency was 3.8%. No neonate suffered from a sickle cell disease (homozygous
      for Hb S or compound heterozygous for Hb S), from another clinically significant
      haemoglobinopathy, or from pyruvate kinase or glucose phosphate isomerase
      deficiency. CONCLUSIONS: Sickle cell disorders should be considered a public
      health problem in Kigali and Butare. A systematic neonatal screening programme
      for those disorders, and to diagnose G6PD deficiency, seems reasonable, but local
      health priorities must be considered. Adapted management of hereditary sickle
      cell and G6PD disorders should be available.

PMID- 17007654
TI  - Screening for sickle cell disease on dried blood: a new approach evaluated on
      27,000 Belgian newborns.
AB  - SETTING: Early diagnosis of sickle cell disease decreases morbidity. However,
      cost-effective screening programmes are not yet available. METHODS: We explored
      the feasibility of systematic screening performed on dried blood harvested from
      five-day-old newborns. RESULTS: A total of 27,010 samples were collected in
      Belgian maternity units between June 2003 and February 2005, and the presence of
      haemoglobin (Hb) C or S in the eluted blood was examined by an enzyme-linked
      immunosorbent assay (ELISA) test performed with a monoclonal antibody detecting
      both mutated forms. As this antibody slightly cross-reacts with Hb A, better
      specificity is achieved if the test is performed not later than day 5. Among the
      27,010 samples, 132 (0.49%) were positive. Molecular biology tests performed on
      dried blood from positive samples showed that 106 of these babies were
      heterozygotes for the Hb S mutation and three were heterozygotes for the Hb C
      mutation, while three newborns were SS homozygotes (0.011%). Seventeen samples
      (0.063%) were false-positives as we could not detect any mutation. CONCLUSIONS:
      We have developed a new immunological approach in the field of haemoglobinopathy
      neonatal screening. This ELISA test is cheap (0.2 euro/test or 1800 euro/detected
      SS homozygote) and could be centralized. Its cost-effectiveness in the whole
      Belgian population is comparable with that of screening for phenylketonuria or
      congenital adrenal hyperplasia. Further improvements should obviously be achieved
      in order to better discriminate heterozygotes and homozygotes, but the
      accessibility and the low cost of the test are relevant arguments for the
      screening extension in a wide range of countries, especially in Central Africa.

PMID- 17007655
TI  - A new method for the classification of invasive cervical cancer screening
      histories.
AB  - OBJECTIVES: To examine the ability of existing classification systems to provide
      screening histories for invasive cervical cancers which can be used in the
      evaluation of the NHS Cervical Screening Programme (NHSCSP), and to provide the
      diagnostic route data item required for the National Cancer Data Set (NCDS).
      METHODS: The ability of existing classification systems to derive unique,
      consistent screening histories for a cohort of invasive cervical cancers
      diagnosed in the West Midlands region in the period 2000-03 was tested using two
      separate timelines for women on normal routine recall (usually 3 or 5 years) and
      those on early recall having had an inadequate, low-grade abnormal or negative
      smear. RESULTS: Neither of the existing classification systems was capable of
      adequately categorizing all invasive cervical cancers. An original classification
      system incorporating features from the existing systems was therefore developed.
      This system includes both a 'screening status' component that essentially
      describes the status of a woman's interaction with the NHSCSP at the time her
      cancer was diagnosed, and a 'screening history' component that describes the
      results of previous screening tests. CONCLUSIONS: National adoption of this new
      screening histories classification system would provide a detailed, consistent,
      nationally comparable screening history for all invasive cervical cancers which
      can be used in the national and regional evaluation of the NHSCSP and in local
      audit by clinical teams supplemented by histology and colposcopy data. The
      classification categories could be collapsed down to provide the diagnostic route
      data item required for the NCDS.

PMID- 17007656
TI  - Self-reported prostate cancer screening in Austria.
AB  - OBJECTIVES: The prevalence of self-reported participation and frequency of
      prostate cancer screening (digital rectal examination (DRE), prostate-specific
      antigen (PSA)) in Austrian men aged 40-79 years in the year 2005 is reported.
      METHODS: In a population-based cross-sectional study, a representative sample of
      500 men was asked whether they ever had heard of early detection of prostate
      cancer by DRE or PSA test and, if so, whether they had ever had a prostate cancer
      screening test during their life, and if so the number of tests and the type of
      physician. RESULTS: Overall, the prevalence of self-reported prostate cancer
      screening was 55.8% (23.7% DRE only). The highest prevalence was observed in the
      age group of 60-69 years with 68.8% (28.1% DRE only). The highest prevalence of
      PSA tests was observed in the age group 70-79 years (40.9%). About 75% of the
      screening tests were performed by urologists. CONCLUSIONS: More than half of the
      target population (men aged 40-79 years) have had at least one prostate cancer
      screening test. Nearly one-third of men have already had one or more PSA tests.
      One-fifth of the PSA tests were requested by general practitioners or internists.

PMID- 17007657
TI  - Diabetes retinopathy screening: audit of equity in participation and selected
      outcomes in South East London.
AB  - OBJECTIVES: To assess uptake of the diabetes retinopathy screening programme in
      South East London and examine variation in attendance and screening outcomes.
      METHODS: Cross-sectional study of patients on a centralized disease register
      invited for retinal screening during 2003. The influence of age, gender,
      deprivation, region of birth and type of diabetes on screening attendance and
      outcomes was assessed. RESULTS: An estimated 46% of residents with known diabetes
      (9750/21,104) were offered digital retinopathy screening during 2003. In all,
      88.9% of patients who were invited for screening attended. Attendance rates were
      significantly lower in younger patients (< or = 40 years), in those with type 1
      diabetes and in patients residing in areas with the highest levels of
      deprivation. A total of 28.9% of patients had background retinopathy or worse
      during 2003. Retinopathy was more common in older patients (>40 years) and in
      individuals with type 1 diabetes after adjusting for other factors. Patients born
      outside the United Kingdom and the Republic of Ireland were significantly more
      likely to present with retinopathy. CONCLUSIONS: This study identified
      considerable inequity in the delivery of a local diabetic retinopathy screening
      programme. Equity audits should form an integral component of ongoing quality
      assurance monitoring of retinopathy screening programmes.

PMID- 17007658
TI  - Cascade screening for familial hypercholesterolaemia: implications of a pilot
      study for national screening programmes.
AB  - OBJECTIVES: To determine what proportion of cases of heterozygous familial
      hypercholesterolaemia would be identified by cascade screening conducted by a
      specialist hospital clinic, and by how much this would increase the prevalence of
      diagnosed cases. SETTING: Hospital clinic serving a population of 605,900 in
      Oxfordshire, UK. METHODS: A specialist nurse obtained details of living first
      degree relatives from 227 adult patients with heterozygous familial
      hypercholesterolaemia currently or previously attending Oxford lipid clinic after
      excluding 79 adults without relatives living in Oxfordshire and 48 children.
      Index cases were asked to invite relatives resident in Oxfordshire for testing.
      RESULTS: A total of 227 index cases had 1075 first-degree relatives, including
      442 adults and 117 children aged < 18 years resident in Oxfordshire. We excluded
      171 previously screened adults and 46 for other reasons. Among 225 eligible adult
      relatives, 28 responders (12%) planned to consult their general practitioner and
      52 (23%) attended the clinic for testing. Parents of 113 children (97%) wanted
      them tested. The positive diagnostic rate was 29% (15/52) in adults and 32%
      (36/113) in children. Screening increased prevalence by 14.4%, from 0.58/1000
      (95% confidence intervals [CI] 0.52-0.65) to 0.67/1000 (95% CI 0.60-0.73),
      representing 33.5% of predicted cases. CONCLUSIONS: Cascade screening conducted
      by a specialist hospital clinic within its population catchment area did not
      substantially increase the prevalence of diagnosed familial
      hypercholesterolaemia. To maximize response rates, clinic staff need to approach
      relatives directly. Validated age, sex and country-specific diagnostic criteria
      should be defined, possibly with access to DNA-based tests, to help resolve
      diagnostic uncertainty.

PMID- 17007659
TI  - Screening for abdominal aortic aneurysm by general practitioners and practice
      based ultrasonographers.
AB  - AIM: To find out if aortic aneurysm screening could be successfully organized
      from a general practice with ultrasound facilities, and to offer a screening
      service to surrounding general practices within a primary health care trust
      (PHCT) in Surrey. METHODS: The study screened men between the ages of 65 and 80
      years for abdominal aortic aneurysm (AAA). The screening project was set up and
      carried out entirely in primary care (in local practices). Funding was received
      from the PHCT; the costs of the screening programme had to fit within this
      budget. RESULTS: There was a 71.7% attendance rate and 4.1% of the screened
      population had an AAA. The screens cost approximately 17.39 pounds per scan.
      CONCLUSIONS: The costs for the screening programme were low, although it is hard
      to find direct comparisons. The attendance rate could be improved, but the
      prevalence of AAA in this study was comparable to those found in hospital-led
      screening trials.

PMID- 17007661
TI  - Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in
      interpreting pregnancy outcome.
AB  - The aim of this study was to assess the clinical value of serum oestradiol
      concentration 8 days after embryo transfer (D8E2) and beta-human chorionic
      gonadotrophin (HCG-beta) concentration 12 days after embryo transfer (D12HCG
      beta) in the prediction of pregnancy and the outcome of pregnancy following
      assisted reproduction, taking into account the day of transfer, which was either
      day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by
      giving quantitative and reliable predictive information instead of non-specific
      uncertainties. A total of 2035 embryo transfer cycles performed between January
      2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic
      pregnancy and first-trimester abortions were classified as non-viable
      pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing
      pregnancies (OP). Significantly higher D8E2 and D12HCG-beta were obtained in D5
      transfers compared with D3 transfers with regard to pregnancy and OP
      (P<or=0.001). For D3 embryo transfers, the cut-off value of D8E2 in predicting OP
      was 130 pg/ml (sensitivity 80%, specificity 72%), compared with 98 mIU/ml
      (sensitivity 89%, specificity 69%) for D12HCG-beta. For D5 embryo transfers, the
      values were 179 pg/ml (sensitivity 79%, specificity 84%) and 257 mIU/ml
      (sensitivity 78%, specificity 81%) respectively. It appears that serum post
      embryo transfer D8E2 and D12HCG-beta concentrations provided clear information
      regarding pregnancy and the outcome of pregnancy following IVF-embryo transfer.

PMID- 17007662
TI  - Precycle administration of GnRH antagonist and microdose HCG decreases clinical
      pregnancy rates without affecting embryo quality and blastulation.
AB  - The outcome of a novel protocol utilizing precycle gonadotrophin-releasing
      hormone (GnRH) antagonist administration and LH activity support with microdose
      recombinant human chorionic gonadotrophin (HCG) was compared to GnRH agonist long
      protocol used in patients undergoing their first ICSI (n=707) or IVF (n=571)
      cycles, which had resulted in one or two blastocyst transfers. In GnRH antagonist
      cycles, cetrorelix acetate (3 mg) was administered s.c. 4 days before FSH
      stimulation and a repeat dose was given when the lead follicular diameter was 13
      14 mm. LH support was provided by recombinant HCG (2.5 microg). Embryo
      progression and blastulation were evaluated using embryo progression indices and
      blastocyst quality scores. The tested protocol demonstrated reduced implantation
      and clinical pregnancy rates as compared with GnRH agonist long protocol,
      although the embryo progression and blastulation parameters and blastocyst
      quality were comparable among the groups. Logistic regression models further
      supported the significant negative impact of GnRH antagonist/microdose HCG
      protocol on clinical pregnancy rates in both ICSI and IVF patients. Assisted
      reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH
      antagonist administration and microdose HCG support resulted in lower
      implantation and clinical pregnancy rates as compared with GnRH agonist cycles,
      although the embryo progression and blastulation parameters were comparable.

PMID- 17007663
TI  - Optimum number of oocytes for a successful first IVF treatment cycle.
AB  - Ovarian stimulation in IVF allows selection of embryos for transfer, but may have
      detrimental effects on oocyte and embryo quality and endometrial receptivity.
      This study investigated the optimal response to ovarian stimulation in terms of
      number of oocytes for achieving pregnancy in a first IVF cycle. Data from 7422
      women who underwent their first IVF cycle for standard indications were analysed.
      All had been treated with exogenous gonadotrophins and gonadotrophin releasing
      hormone (GnRH) agonist co-treatment in a long down-regulation protocol between
      1990 and 1995. Pregnancy rates in relation to the number of obtained oocytes were
      adjusted for age, fecundity, subfertility cause, gonadotrophin dosage, type of
      luteal support, and number of transferred embryos by multivariate analysis. Of
      the 7422 women who underwent oocyte retrieval, overall 85% had an embryo transfer
      and 24% conceived. The highest pregnancy rates per embryo transfer and per
      started cycle were observed when 13 oocytes were obtained (31 and 28%,
      respectively). This study supports the concept of an optimal range of oocytes
      obtained in response to ovarian stimulation for IVF, below and above which
      outcomes are compromised.

PMID- 17007665
TI  - Transcriptional profiling of granulosa cells from a patient with recurrent empty
      follicle syndrome.
AB  - Empty follicle syndrome (EFS) is characterized by the absence of oocytes after
      apparently normal follicular development and the pathogenesis of this syndrome is
      not well characterized. The aim of this study was to analyse whole gene
      expression of granulosa cells (GC) from a patient with recurrent EFS by using
      Affymetrix GeneChip. A total of 160 genes were identified as being differentially
      expressed (by at least two-fold) between EFS GC and the control GC. Most of the
      differentially expressed genes were involved in cell growth and death. Among
      these were MAPK3, which plays an important role in the inhibition of apoptosis,
      was down-regulated 2.3-fold in EFS GC. Moreover, secretory phospholipase A2 and
      transforming growth factor receptor II, key regulators of cell death pathway,
      were down-regulated 3.54- and 2.82-fold respectively in EFS. Gene expression of
      granulosa cells from the EFS patient was significantly altered. The absence of
      the oocytes might be due to the increased apoptotic gene expression and the
      reduction of transcripts whose products are responsible for healthy follicular
      growth. Gene expression analyses might be a useful technique in identifying
      markers to follow a healthy follicular maturation and understanding the events
      that lead to EFS.

PMID- 17007666
TI  - p53 tumour suppressor gene polymorphism is associated with recurrent implantation
      failure.
AB  - Implantation failure is the most frequent cause of lack of pregnancy after IVF
      and embryo transfer. Successful implantation requires trophoblastic growth into
      the endometrium to stimulate its own blood supply. The p53 tumour suppressor gene
      has been shown to regulate cell growth and induce angiogenesis. Therefore, the
      prevalence of p53 codon 72 polymorphism was investigated among women with a
      history of recurrent implantation failure to determine whether this polymorphism
      may serve as a risk factor for implantation failure. DNA was extracted from the
      buccal swabs obtained from 70 women experiencing implantation failure and
      polymerase chain reaction amplification of p53 arginine (Arg) 72 and proline
      (Pro) 72 variants were performed. The frequency of homozygous Arg and Pro or
      heterozygous Arg/Pro genotypes was compared with frequencies among 205 women
      experiencing recurrent pregnancy loss and 20 control women. The frequency of
      Pro72 was significantly higher (P=0.003) among women experiencing recurrent
      implantation failure compared with women experiencing recurrent miscarriage and
      with control women. It is concluded that p53 codon 72 polymorphisms may serve as
      a susceptibility factor affecting the chances of recurrent implantation after IVF
      or embryo transfer.

PMID- 17007667
TI  - D & C and dead baby.

PMID- 17007668
TI  - Comparison of embryo quality between sibling embryos originating from frozen or
      fresh oocytes.
AB  - Human embryo cryopreservation techniques allow storage of surplus embryos created
      during assisted reproduction procedures; however, the existence of these same
      surplus embryos has sparked further debate. What can be their fate once they are
      no longer desired by their parents, or if the parents are deceased? Thus, the
      level of interest in the cryopreservation of oocytes has increased, as has the
      necessity for further scientific study. This study had the objective of comparing
      embryo quality from 16 women who underwent intracytoplasmic sperm injection,
      where approximately half of the retrieved oocytes per cycle were inseminated
      fresh after collection, and the remainder cryopreserved for subsequent
      fertilization. Normal fertilization rates were not significantly different
      between the two oocyte-treatment groups. There was no significant difference in
      the frequency of good quality embryos (morphology grades I and II) on the second
      day of laboratory evaluation between embryos derived from the two oocyte
      treatment groups. It is interesting to note that embryo transfer from fresh
      oocytes produced no pregnancies, which shows that even embryos derived from
      frozen oocytes that are fragmented or have a slower cleavage rate are viable
      embryos, capable of producing healthy babies.

PMID- 17007670
TI  - Role of embryo quality in predicting early pregnancy loss following assisted
      reproductive technology.
AB  - Early pregnancy loss (EPL) significantly reduces the initial success rate of
      assisted reproduction treatments and increases the psychological burden on the
      patient. The aim of the current study was to investigate the association between
      embryo quality and EPL in IVF. A retrospective study of 1471 women undergoing IVF
      between July 2000 and October 2004 was performed. Multivariate logistic
      regression models evaluated the effect on EPL of the woman's age, type and cause
      of infertility, endometrial thickness on the day of oocyte retrieval, performance
      of intracytoplasmic sperm injection, number of transferred embryos, embryo
      quality as assessed by the number of blastomeres in the leading transferred
      embryo at day 3, and the percentage of fragmentation. The 2902 oocyte retrieval
      embryo transfer cycles resulted in 816 pregnancies (28.1%; 705 women)
      constituting the study cohort. Of these, 259 pregnancies (31.7%) ended in EPL and
      557 (68.3%) in ongoing pregnancies. EPL risk was significantly associated with
      advanced (>35 years) maternal age (OR=1.53; 95% CI 1.12-2.09) and five or fewer
      blastomeres in the leading embryo transferred at day 3 (OR=1.82; 95% CI 1.16
      2.85). In conclusion, the quality of transferred embryos, as assessed by the
      total number of blastomeres in the leading transferred embryo, and maternal age
      are predictors of EPL.

PMID- 17007671
TI  - Right varicocele and hypoxia, crucial factors in male infertility: fluid
      mechanics analysis of the impaired testicular drainage system.
AB  - Varicocele is considered a predominantly unilateral left-sided disease. However,
      since male fertility is preserved with only one healthy testis, infertility
      perforce represents bilateral testicular dysfunction. It was hypothesized that:
      (i) right varicocele cannot be diagnosed by palpation and therefore has not been
      treated in the past by the traditional treatment, and (ii) right varicocele
      causes impaired oxygen supply in the right testicular microcirculation, leading
      to germ cell degeneration. This study performed venographies of both right and
      left internal spermatic veins during the treatment of 840 infertile men with
      varicocele and analysed the results using tools of fluid mechanics.
      Histopathology of the right testis revealed stagnation of blood flow and
      degenerative changes attributed to lack of adequate oxygenation in all testicular
      cell types. Right varicocele was found in the vast majority of the patients. We
      found that due to the destruction of one-way valves, pathologic hydrostatic
      pressure is produced in the testicular venous microcirculatory system about five
      times higher than normal, exceeding arteriolar pressure. The pressure gradient
      between the arterioles and venules in the testicular tissue is therefore
      reversed, leading to persistent hypoxia. Right varicocele, although undetected,
      is prevalent in infertile men with varicocele, hence only bilateral occlusion of
      the internal spermatic veins, including the associated bypasses, eliminating the
      pathologic hydrostatic pressure will lead to resumption of arterial blood flow in
      the testicular microcirculation.

PMID- 17007673
TI  - Assessment of endocervical and endometrial damage inflicted by embryo transfer
      trial: a hysteroscopic evaluation.
AB  - The aim was to assess the endocervical and endometrial damage inflicted by embryo
      transfer trial using office hysteroscopy. Seventy-five consecutive infertile
      women who underwent office hysteroscopy were enrolled. Hysteroscopy was performed
      immediately after embryo transfer trial. The relationship between clinical
      perception of easiness of transfer, presence of blood on the catheter, degree of
      endocervical and endometrial damage was examined. In the difficult transfer
      group, minor and moderate endocervical lesions were noted in 35% and 24% of the
      cases, respectively. The respective figures for the easy transfer group were 19%
      and 3% (P>.05). There was a statistically significant concordance between the
      perceived difficulty of transfer and degree of endometrial damage (P<0.05). Of
      interest, in the easy transfer group, 32% of the patients had minor, 3% moderate
      and 65% no endometrial damage. The respective figures were 42%, 29% and 29% in
      the difficult transfer group. There was blood on the catheter in 25%, 56% and 71%
      of the easy, moderate and difficult transfer groups, respectively. There was a
      statistically significant concordance between the perceived difficulty of embryo
      transfer and presence of blood on the catheter (P<0.05). These results suggest
      that clinical perception of difficulty of transfer and the presence of blood on
      the catheter are directly associated with endometrial disruption.

PMID- 17007672
TI  - Outcome of 1114 ICSI and embryo transfer cycles of women 40 years of age and
      over.
AB  - The purpose of this study was to contribute to the development of strategies to
      obtain acceptable outcomes in assisted reproduction treatments in women over 40
      years of age. A retrospective study was carried out on the database of the German
      Hospital in Istanbul using data from the years 1997 to 2004. A total of 1114
      embryo transfer cycles were assessed. The pregnancy, implantation and delivery
      rates of the assessed population were 18.2, 8.3 and 10.9% respectively. The
      results showed that the demographics and outcome of cycles of women at 40 years
      differed significantly from those over 40. Cycles in which six or more oocytes
      were retrieved displayed better characteristics and outcome than those with five
      or fewer. The clinical pregnancy and delivery rates after transfer of three
      embryos were similar to four or more. Therefore, women over 40 years with a good
      ovarian response and at least three embryos available for transfer have an
      acceptable pregnancy and delivery rate with a low multiple pregnancy risk.

PMID- 17007674
TI  - Control and function of uterine peristalsis during the human luteal phase.
AB  - Rhythmic peristaltic contractions of the muscular wall of the non-pregnant uterus
      can be demonstrated throughout the menstrual cycle, with a maximum just before
      ovulation. However, not only during the follicular phase but also during the
      luteal phase, the uterus shows remarkable contractile activity. The present study
      was conducted in order to examine uterine peristaltic activity and its function
      during the luteal phases of the human menstrual cycle. The results of vaginal
      sonography of uterine peristalsis, of hysterosalpingoscintigraphy and of the
      documentation of the sites of embryo implantation in natural and artificial
      cycles have shown that uterine peristalsis during the luteal phase is controlled
      by systemic and probably even more by local hormonal secretion from the fresh
      corpus luteum, and facilitates the fundal implantation of the blastocyst
      predominantly ipsilateral to the site of the dominant ovarian structure.
      Furthermore, this study suggests that the defence against the infiltration and
      inflammation of the upper genital tract, and thus the degradation of the
      implanted embryo, represents a further and phylogenetically old and genuine
      function of the archimetra, which in placentalia was modified in order to
      participate in the control of invasion of the endometrium by the trophoblast.

PMID- 17007675
TI  - Implantation sites after embryo transfer into the central area of the uterine
      cavity.
AB  - A total of 63 pregnancies (47 singleton, 15 twin, 1 triplet) from
      intracytoplasmic sperm injection cycles were analysed. In all embryo transfers,
      the catheter was introduced into the endometrial cavity guided by abdominal
      ultrasound, with the catheter tip placed at the middle point of the endometrial
      cavity. Gestational sacs (GS) were located 21-24 days after transfer (gestational
      age=5 weeks) by two-dimensional and three-dimensional transvaginal ultrasound.
      The uterine cavity was divided into three parts: upper, middle and lower.
      Furthermore, the upper region was subdivided into right, middle and left areas,
      and the middle region was subdivided into right and left areas. The frequency of
      gestational sacs in each area was evaluated. In singleton pregnancies 66.0%
      (31/47) of the GS were detected in the upper region, 29.8% (14/47) in the middle
      region and 4.2% (2/47) in the lower region. In multiple pregnancies (twins and
      triplet) 45.5% (15/33) of the GS were detected in the upper region, 51.5% (17/33)
      in the middle region and 3.0% (1/33) in the lower region. In conclusion, the
      results demonstrate that when embryos are transferred to the central area of the
      uterine cavity there is an increase in implantation rate in the middle region
      compared with the rate expected in naturally conceived pregnancies (9-15%).

PMID- 17007676
TI  - Repository of human embryonic stem cell lines and development of individual
      specific lines using stembrid technology.
AB  - A human embryonic stem cell (HESC) line repository has been established,
      containing HESC lines with normal and abnormal genotypes, providing the source
      for studying the primary mechanisms of genetic disorders at the cellular level.
      Because the outcome of HESC transplantation treatment depends on access to human
      leukocyte antigen identical stem cells, the development of individual specific
      HESC was initiated, using the original stembrid technology, which is based on the
      hybridization of adult somatic cells with cytoplast of HESC lines. The data
      presented here demonstrate feasibility of this approach in the future development
      of HESC transplantation treatment of genetic and acquired disorders. The
      established HESC repository presently contains 166 HESC lines, including 127 with
      normal genotype and 39 with genetic and chromosomal disorders.

PMID- 17007678
TI  - Totipotency, cell differentiation and reprogramming in humans.
AB  - Understanding the molecular mechanisms defining totipotency and cell
      differentiation in humans is a promising strategy in order to expand knowledge
      about reprogramming. Totipotency and the very first steps of cell differentiation
      can be studied well in early human embryos. Based on analysis of marker genes
      such as Oct-4 and -HCG, blastomeres seem to differ in their potency and can be
      regarded as lineage-specific stem cells as early as the 4-cell stage. The
      allocation of these stem cells to specific fates might hereby follow a pattern
      reminiscent of animal and vegetal poles. On the opposite end of the developmental
      spectrum, differentiated human cells can be used as a means of studying nuclear
      reprogramming. Intact human 293T kidney cells and primary leukocytes were
      reprogrammed towards a more undifferentiated state by Xenopus laevis egg extract.
      Molecular screens identified the chromatin-remodelling ATPase BRG1 as a factor
      required for this process. Based on these results, more efficient reprogramming
      protocols allowing for the generation of fully differentiated or undifferentiated
      human cells for clinical application may be developed.

PMID- 17007679
TI  - Recovery and amplification of placental RNA from dried maternal blood spots:
      utility for non-invasive prenatal diagnosis.
AB  - Methods utilizing circulating cell-free RNA in plasma have clinical applications
      for cancer and prenatal genetic analysis. Given these potential roles, the
      feasibility of detecting placental specific RNA in dried maternal blood spots
      after storage at room temperature for varying lengths of time was investigated.
      Using real-time polymerase chain reaction (PCR), positive amplification of
      placental-specific beta-human chorionic gonadotrophin transcripts was
      demonstrated in nine of 11 dried blood samples from first and second trimester
      pregnancies stored at room temperature for up to 4 weeks. This work demonstrates
      feasibility in isolation and amplification of placental mRNA using dried maternal
      blood spots. With the development of fetal and placental RNA markers, this
      approach would allow simplified collection, transport, and storage of samples for
      prenatal genetic diagnosis and pregnancy related complications.

PMID- 17007681
TI  - Potential clinical applications using stem cells derived from human umbilical
      cord blood.
AB  - There is an abundance of clinical applications using human umbilical cord blood
      (HUCB) as a source for stem cell populations. Other than haematopoietic
      progenitors, there are mesenchymal, endothelial stem cells and neuronal
      precursors, in varying quantities, that are found in human umbilical cord blood.
      These may be useful in diseases such as immune deficiency and autoimmune
      disorders. Considering issues of safety, availability, transplant methodology,
      rejection and side effects, it is contended that a therapeutic stem cell
      transplant, utilizing stem cells from HUCB, provides a reliable repository of
      early precursor cells that can be useful in a great number of diverse conditions.
      Drawbacks of relatively smaller quantities of mononucleated cells in one unit of
      cord blood can be mitigated by in-vitro expansion procedures, improved in-vivo
      signalling, and augmentation of the cellular milieu, while simultaneously
      choosing the appropriate transplantation site and technique for introduction of
      the stem cell graft.

PMID- 17007682
TI  - Egg harvesting for stem cell research: medical risks and ethical problems.
AB  - Increasingly, researchers are seeking eggs from young women to be used for embryo
      cloning procedures. The harvesting of multiple eggs often involves the
      administration of drugs that have not been approved for this purpose. Also these
      drugs have not been adequately studied for their long-term effects on women
      despite research providing some evidence of significant harm to women in both the
      short and long term. Current practices follow a historical pattern of exposing
      women to risks that ultimately prove unacceptable. In addition, egg harvesting is
      taking place in a research climate marked by conflicts of interest, the
      misleading use of language to describe research goals, and a commercial push that
      may lead to the exploitation of young women. In this article, we outline these
      matters and explain how they are leading to an international campaign for a
      moratorium on egg harvesting for cloning purposes.

PMID- 17007685
TI  - Human embryonic stem cell culture: current limitations and novel strategies.
AB  - Embryonic stem cells (ESC) are multipotent cells isolated from blastocyst-stage
      preimplantation embryos. Since their first culture in 1998, human ESC have
      revolutionized reproductive and regenerative medicine by allowing the
      establishment of detailed molecular and therapeutic models for certain metabolic
      pathways and life-threatening disorders. They also offer significant
      contributions to genetics and pharmacology in designing and analysing disease
      models that can be closer to in vivo than any other procedures available.
      However, the procedures by which they are obtained and manipulated also create
      intense ethical and social debates worldwide. This article discusses the current
      limitations and recent advances in isolation, culture and differentiation of
      human ESC from the laboratory perspective.

PMID- 17007686
TI  - Defective implantation and placentation: laying the blueprint for pregnancy
      complications.
AB  - Normal implantation and placentation is critical for pregnancy success. Many
      pregnancy-related complications that present late in gestation (such as pre
      eclampsia and preterm labour) appear to have their origins early in pregnancy
      with abnormalities in implantation and placental development. Implantation is
      characterized by invasion of the maternal tissues of the uterus by fetal
      trophoblast, and the degree to which trophoblast invades these tissues appears to
      be a major determinant of pregnancy outcome. Excessive invasion can lead to
      abnormally firm attachment of the placenta to the myometrium (placenta accreta)
      with increased maternal and perinatal morbidity. Inadequate invasion,
      specifically restricted endovascular invasion, has been implicated in the
      pathophysiology of such conditions as pre-eclampsia (gestational proteinuric
      hypertension), preterm premature rupture of membranes, preterm labour, and
      intrauterine growth restriction. The molecular and cellular mechanisms
      responsible for implantation remain enigmatic. This review will include an
      overview of implantation followed by a discussion of a number of molecular
      mechanisms implicated in defective implantation and placentation including the
      role of decidual prostaglandins and haemorrhage in regulating trophoblast
      invasion. An improved understanding of the molecular mechanisms responsible for
      abnormal implantation and placentation will likely improve clinicians' abilities
      to treat disorders that occur along this continuum, including infertility,
      recurrent pregnancy loss, pre-eclampsia, and preterm birth.

PMID- 17007688
TI  - Chronic conditions and the developing world: a contribution to the evidence base.

PMID- 17007689
TI  - The hard work of being ill.

PMID- 17007691
TI  - Researching chronic childhood illness: the example of childhood cancer.
AB  - OBJECTIVES: To provide an overview of issues raised by conducting research in the
      area of chronic childhood illness, using the example of childhood cancer.
      METHODS: This literature review used informal methods. RESULTS: Children with
      cancer and their families may participate in a wide variety of studies in
      different research traditions, including social science studies, epidemiological,
      biological and genetic research, and clinical trials. Different concerns about
      research participation have been raised in these different contexts. Sociological
      debate has tended to characterize exclusion from research as a manifestation of
      assumptions of poor competence on the part of children, and to see inclusion in
      research as a means of restoring proper balance in power relations and giving
      children a voice. The ethical imperative within clinical research, on the other
      hand, has been in favour of protection of individuals from risk or direct harm.
      Lack of consensus on issues such as the status of children's consent for research
      participation persists, in part because debates have taken place within rather
      than across disciplinary boundaries, and in part because of a tendency to debate
      issues as ethical principles in an empirical vacuum. The lack of research on the
      experiences and views of those asked to take part in childhood cancer research is
      striking. DISCUSSION: It is important that debates about the involvement of
      children in research are informed by high-quality social science research and by
      interdisciplinary dialogue.

PMID- 17007692
TI  - Researching chronic childhood illness: autonomy or beneficence?

PMID- 17007693
TI  - Ethical issues related to the increased emphasis on children participating in
      research.

PMID- 17007694
TI  - Researching childhood illness: the need for methodological studies.

PMID- 17007695
TI  - Self-managing and managing self: practical and moral dilemmas in accounts of
      living with chronic illness.
AB  - BACKGROUND: Patient education self-management programmes draw on sociological
      understanding of experiencing single chronic illnesses, but health practitioners
      do not always recognize the tensions and ambiguities permeating individuals'
      management experiences, particularly for those with multiple morbidity. The aim
      of this study was to illuminate how people negotiate multiple chronic illness,
      and everyday life. METHODS: A sample of 23 people in their early 50s was
      recruited from a community health survey in Scotland. The participants had four
      or more chronic illnesses and were interviewed twice. The qualitative data that
      were generated highlighted the impact of illness and associated management
      strategies, as people attempted to continue familiar lives. Analysis was based on
      constant comparison and informed by a narrative approach. RESULTS: People used
      multiple techniques to manage symptoms and conveyed a moral obligation to manage
      'well'. However, maintaining valued social roles, coherent identities and a
      'normal life' were prioritized, sometimes over symptom containment. This led to
      tensions, and participants faced moral dilemmas as they self-managed. DISCUSSION:
      Self-management policies, programmes and healthcare practitioners need to
      recognize the tensions that people experience as they negotiate symptoms, valued
      social roles, positive identities, and daily life. Addressing these issues may
      improve opportunities to support patients in particular contexts, and enhance
      self-management.

PMID- 17007696
TI  - 'When I am together with them I feel more ill.' The stigma of multiple sclerosis
      experienced in social relationships.
AB  - OBJECTIVES: We explored the stigma that people with multiple sclerosis (MS)
      experienced in social relationships. Informed by the symbolic integrationist
      paradigm, this sociological study focuses on the creation of personal identity
      through interaction with others. The symbolic interactionist account of stigma
      examines the meaning and reality being negotiated in communication with others.
      METHODS: Fourteen people with MS and their relatives were interviewed. The
      unstructured interviews were tape-recorded, transcribed and coded in accordance
      with the procedure of grounded theory. RESULTS: Informants reported being ignored
      or, in contrast, having people overemphasize MS in interpersonal encounters.
      Although people tried to act tactfully, these acts were experienced as crucial
      stigmatizing. Informants were coping to counteract stigmatizing experiences in
      social relationships. DISCUSSION: People with MS perceive that their bodily
      performance and impression management is being judged in interpersonal
      encounters. Being ignored or perceiving that MS is overemphasized indicates the
      dilemma of managing stigma in social networks. Consequently, during interaction
      and in social relationships, people with MS experience a sense of 'feeling more
      ill'. This paper describes strategies of networking to affirm self and identity.

PMID- 17007697
TI  - Remaking the future: contemplating a life with chronic widespread pain.
AB  - OBJECTIVES: This paper reports findings from a larger study that aimed to explore
      how people with chronic widespread pain experience, understand and make meaning
      of their 'condition', and attempt to influence or exert control over their pain.
      This included an exploration of sufferers' understanding of the past and future
      as well as of their present situation. METHODS: A combination of data generation
      methods was used, including lifegrid interviews, diaries and diary interviews,
      with eight people with chronic widespread pain. Five family members also
      participated in interviews. Analytical methods were based on interpretative
      phenomenological analysis (IPA). RESULTS: With regard to their views about the
      future, participants could be categorized into those who were 'optimistic'
      ('things can only get better'), those who were pessimistic ('things will get
      worse'), and those who were overwhelmed with uncertainty about the future.
      Uncertainty was a dominant feature in all the accounts of the future. DISCUSSION:
      The pervading uncertainty of chronic widespread pain, in which there is no
      framework for the trajectory of the condition, affects perceptions of the future
      and makes planning for the future difficult. The findings also raise the question
      of how this makes chronic widespread pain different from other chronic conditions
      in terms of understanding of chronicity, time and future, and hence 'acceptance'.

PMID- 17007698
TI  - Factors important for the measurement of social comparison in chronic illness: a
      mixed-methods study.
AB  - OBJECTIVES: The aim of this study was to examine social comparison in illness
      using a mixed-methods approach that combined inductive exploration of how people
      used social comparison in this self-help group with a quantitative study of
      social comparison processes and their relationship to quality of life. METHODS:
      The qualitative study involved 15 semi-structured interviews with people with
      Meniere's disease. Themes from the analysis of the interviews informed the
      development of the Social Comparison in Illness Scale (SCIS), which was then
      validated in a questionnaire study, in which participants with Meniere's disease
      (n = 196) completed the SCIS, the previously validated Identification/Contrast
      social comparison scale, and the SF-36 health status questionnaire. RESULTS: The
      qualitative study uncovered a wide range of forms of social comparison, including
      upward, downward and lateral comparison on illness and coping dimensions, as well
      as comparing solely for informational purposes. The quantitative study indicated
      that these varied directions and dimensions of social comparison could be mapped
      onto five reliable categories that were related to quality of life: upward
      positive and downward positive comparison, upward negative and downward negative
      comparison, and comparing for information. DISCUSSION: These analyses highlight
      the complexity of socially comparing in chronic illness, but also confirm the
      validity of the Identification/Contrast model of social comparison in this
      context.

PMID- 17007699
TI  - Qualitative study of an intervention for depression among patients with diabetes:
      how can we optimize patient-professional interaction?
AB  - OBJECTIVES: To describe the communication between the depression care specialist
      (DCS) nurses and patients with both depression and diabetes in an intervention
      study. Our aims were to inform both the quantitative findings of the present
      trial and the design of future primary care intervention studies. METHODS:
      Qualitative content analysis of consultations between DCS nurses and patients in
      nine primary care clinics. RESULTS: Patients experienced a wide range of
      physical, social and psychological problems. The DCS nurses employed a range of
      interventions in addition to the problem-solving and case-management skills that
      formed the basis of this intervention. CONCLUSIONS: Patients sometimes posed
      difficulties in being unable to understand the treatment, unprepared to engage
      with a new treatment and unready (or even unable) to acquire new skills. To
      optimize the interaction between patient and professional in the case management
      of depression and diabetes, training should provide guidance in the use of
      different models of care (medical and psychological), help case managers to
      identify and negotiate problem scenarios and combine an active model of therapy
      such as problem-solving treatment for primary care (PST-PC) with elements from
      motivational interviewing, ensure effective engagement in treatment, and
      specifically explore how interaction between depression and diabetes might result
      in adverse outcomes.

PMID- 17007701
TI  - Gastro-oesophageal reflux disease: a re-appraisal.

PMID- 17007702
TI  - General practice specialty training: an innovative programme.

PMID- 17007703
TI  - Preferences for access to the GP: a discrete choice experiment.
AB  - BACKGROUND: Access to primary care services is one of the key components of the
      NHS Plan which states that patients should be able to see a health professional
      within 24 hours and a GP within 48 hours. However, it is not clear how patients
      value speed of access in comparison with other aspects of primary care. AIM: To
      investigate patient preferences when making an routine appointment for a GP, and
      to describe the trade-offs and relationships between speed of access, choice of
      time and choice of doctor in different patient groups. DESIGN OF STUDY: Discrete
      choice experiment. SETTING: Adults consulting a GP in six general practices in
      Sunderland. METHOD: Choice sets based on three attributes (time to appointment,
      choice of time, choice of doctor) were presented in a self-completion
      questionnaire. RESULTS: We obtained 6985 observations from 1153 patients. We
      found that the waiting time to make an appointment was only important if the
      appointment is for a child or when attending for a new health problem. Other
      responders would trade-off a shorter waiting time and be willing to wait in order
      to either see their own choice of doctor or attend an appointment at their own
      choice of time. For responders who work, choice of time is six times more
      important than a shorter waiting time and they are willing to wait up to 1 day
      extra for this. Those with a long-standing illness value seeing their own GP more
      than seven times as much as having a shorter waiting time for an appointment and
      will wait an extra 1 day for an appointment with the GP of their choice, women
      will wait an extra 2 days, and older patients an extra 2.5 days. CONCLUSION:
      Speed of access is of limited importance to patients accessing their GP, and for
      many is outweighed by choice of GP or convenience of appointment.

PMID- 17007704
TI  - How are different types of continuity achieved? A mixed methods longitudinal
      study.
AB  - BACKGROUND: In the context of developments in healthcare services that emphasise
      swift access to care, concern has been expressed about whether and how continuity
      of care, particularly interpersonal continuity, will continue to be achieved.
      AIM: To explore how patients regard and use primary care services in relation to
      continuity of provider and access to care, to identify factors that promote or
      hinder their success in achieving their preferences, and to describe what this
      means for how different types of continuity are achieved. DESIGN OF STUDY:
      Longitudinal, mixed methods. SETTING: Community in London and Leicester. METHOD:
      Purposive sample of 31 patients recruited from general practices, walk-in centres
      and direct advertising. Data collection involved in-depth interviews,
      consultation record booklets completed over 6 months and general practice records
      for the year including the study period. Data were analysed qualitatively.
      RESULTS: Four patterns were identified in the way patients used primary care.
      These were shaped by their own preferences, by the organisation and culture of
      their primary care practices, and by their own and their provider's efforts to
      achieve their preferences. Different configurations of these factors gave rise to
      different types of continuity. Patients were not always able to achieve the type
      they wanted. Patients with apparently similar consulting patterns could
      experience them differently. CONCLUSION: Within a programme of modernisation,
      policies that promote a commitment to meeting the preferences of different
      patients with flexibility and understanding are most likely to provide continued
      support for interpersonal and other types of continuity of care.

PMID- 17007705
TI  - Clinical features of prostate cancer before diagnosis: a population-based, case
      control study.
AB  - BACKGROUND: Even in areas where screening is available, many prostate cancers are
      diagnosed after the symptoms begin. However, the risk posed by particular
      symptoms is largely unknown, especially in unselected populations such as primary
      care. AIM: To identify and quantify the features of prostate cancer before
      diagnosis, both individually and in combination. DESIGN OF STUDY: Population
      based case-control study. SETTING: All 21 general practices in Exeter, Devon, UK.
      METHODS: We studied all 217 prostate cancer patients diagnosed between 1998 and
      2002, and 1080 male controls, matched by age and general practice. The full
      medical record for 2 years before diagnosis was coded, using the International
      Classification of Primary Care. We calculated odds ratios for variables
      independently associated with cancer, using conditional logistic regression, and
      calculated the positive predictive values for these, both individually and in
      combination. RESULTS: Eight features were associated with prostate cancer before
      diagnosis. Their positive predictive values against a background risk of 0.35%
      were: urinary retention 3.1% (95% confidence interval [CI] = 1.5 to 6.0);
      impotence 3.0% (95% CI = 1.7 to 4.9); frequency 2.2% (95% CI = 1.3 to 3.5);
      hesitancy 3.0% (95% CI = 1.5 to 5.5); nocturia 2.2% (95% CI = 1.2 to 3.6);
      haematuria 1.0% (95% CI = 0.57 to 1.8); weight loss 0.75% (95% CI = 0.38 to 1.4);
      abnormal rectal examination, deemed benign 2.8% (95% CI = 1.6 to 4.6); abnormal
      rectal examination, deemed malignant 12% (95% CI = 5.0 to 37): all P <0.001,
      except for hesitancy P = 0.032, nocturia P = 0.004 and haematuria P = 0.009. Loss
      of weight, impotence, frequency and abnormal rectal examination remained
      associated with cancer after excluding the final 180 days from analysis.
      CONCLUSION: Most men with prostate cancer present with symptoms. The predictive
      values for these symptoms will help guide GPs and patients about the value of
      further investigation.

PMID- 17007706
TI  - Predicting colorectal cancer risk in patients with rectal bleeding.
AB  - BACKGROUND: Rectal bleeding is an important symptom of colorectal cancer but has
      low predictive value in primary care. AIM: To determine which characteristics of
      rectal bleeding, along with other factors, are predictive of colorectal cancer.
      DESIGN OF STUDY: Observation study of patients with rectal bleeding referred to
      an open-access diagnostic clinic. SETTING: Primary care, southern England.
      METHOD: Symptom data were collected, using a self-completed questionnaire.
      Logistic regression techniques were used to determine predictors of colorectal
      cancer. RESULTS: There were 604 patients in the study and 22 (3.6%, 95%
      confidence interval [CI] = 2.0% to 5.2%) were diagnosed with colorectal cancer.
      Significant predictors of colorectal cancer were found to be age (<50 years: odds
      ratio [OR] = 1; 50-69 years: OR = 5.1, 95% CI = 1.4 to 18.6; > or = 70 years: OR
      = 8.2, 95% CI = 2.1 to 31.8) and blood mixed with the stool (Likelihood ratio
      [LR] 1.5; adjusted OR = 3.8; 95% CI = 1.4 to 10.5). Presence of haemorrhoids
      associated with bright red bleeding not mixed with stool reduced the likelihood
      of cancer (OR = 0.4, 95% CI = 0.1 to 1.2) but did not eliminate it--a cancer was
      present in 2% of patients with these symptoms. CONCLUSION: Patient-reported type
      of rectal bleeding as an isolated symptom has insufficient diagnostic value to be
      useful in general practice. By studying referred patients, we may even have
      overestimated its value. At best, it could be useful as a component of a
      composite symptom score to guide referral decisions.

PMID- 17007707
TI  - A randomised controlled trial of motivational interviewing for smoking cessation.
AB  - BACKGROUND: Motivational interviewing is a technique used to promote change in
      addictive behaviour, initially used to treat alcoholism. Despite this, its
      effectiveness has not been sufficiently demonstrated for giving up smoking. AIM:
      The aim of the study was to establish whether motivational interviewing, compared
      with anti-smoking advice, is more effective for giving up the habit. DESIGN OF
      STUDY: Randomised controlled trial. SETTING: Primary care in Albecete, Spain.
      METHOD: Random experimental study of 200 smokers assigned to two types of
      interventions: anti-smoking advice (n = 86) and motivational interviewing (n =
      114). Subjects in both groups were offered bupropion when nicotine dependency was
      high (Fagerstrom score >7). The success rate was evaluated by intention to treat;
      point prevalence abstinence was measured 6 and 12 months post intervention by
      personal testimony, confirmed by means of CO-oximetry (value < 6ppm). RESULTS:
      The measure of effectiveness of the treatment for giving up smoking after both 6
      and 12 months, showed that the motivational interviewing action was 5.2 times
      higher than anti-smoking advice (18.4 % compared to 3.4%; 95% confidence interval
      = 1.63 to 17.13). CONCLUSION: The results of our study show that motivational
      interviewing is more effective than brief advice for giving up smoking.

PMID- 17007708
TI  - Feasibility study of a primary care-based model for stroke aftercare.
AB  - BACKGROUND: A new primary care model for stroke aftercare has been developed to
      address the longer-term needs of patients who have had a stroke and their
      families. AIM: To test the feasibility and acceptability of the new model on
      patients who have had a stroke and their carers. DESIGN OF STUDY: An
      observational feasibility study. SETTING: Patient and carer assessments and
      interviews conducted in patients' homes. METHOD: Patients who have had a stroke,
      and their carers, were assessed using a purposely developed primary care stroke
      model. Qualified health- and social-care professionals acted as stroke care
      coordinators and carried out the assessments. Four evaluations were undertaken as
      part of the study: analysis of care plans, a survey of unmet needs, focus group
      sessions for staff, and patient/carer interviews. RESULTS: Forty-seven patients
      and 21 carers were recruited to the study. Analysis of care plans indicated that
      the assessment process was successful in identifying patient and carer problems
      (n = 219). Actions were instigated against 190 of these problems and, at 3 months
      after the assessment, 75% of the problems had been resolved. Patients/carers
      thought that the review process would be more valuable if conducted sooner after
      hospital discharge. CONCLUSION: The model was acceptable to professionals,
      encouraging them to work in a manner more consistent with the expressed needs of
      patients and carers who were adjusting to the longer-term impact of stroke.
      Essential aspects informing the care process were also identified. Further work
      is now required to investigate the effects of the intervention on patient and
      carer outcomes.

PMID- 17007710
TI  - High-dose inhaled corticosteroid use in childhood asthma: an observational study
      of GP prescribing.
AB  - Inhaled corticosteroids are effective and safe treatments for childhood asthma in
      standard doses, yet at high dosages they may be associated with adverse events
      and suboptimal outcomes; add-on therapy is, therefore, recommended to minimise
      their use. We quantified prescribing of high-dose inhaled corticosteroids and add
      on therapy in children in July 2003 and found that high-dose inhaled
      corticosteroids were prescribed to 10% of children aged 5-11 years and 6% of
      under-5's who were treated for asthma. Add-on therapy was lacking for almost half
      of these individuals. Some children were receiving treatment not in accord with
      current licences and evidence-based recommendations and, as such, may be at risk
      of adverse outcomes.

PMID- 17007709
TI  - The effects of a team-based continuous quality improvement intervention on the
      management of primary care: a randomised controlled trial.
AB  - AIM: To study the effects of a team-based model for continuous quality
      improvement (CQI) on primary care practice management. DESIGN OF STUDY:
      Randomised controlled trial. SETTING: Twenty-six intervention and 23 control
      primary care practices in the Netherlands. METHOD: Practices interested in taking
      part in the CQI project were, after assessment of their practice organisation,
      randomly assigned to the intervention or control groups. During a total of five
      meetings, a facilitator helped the teams in the intervention group select
      suitable topics for quality improvement and follow a structured approach to
      achieve improvement objectives. Checklists completed by an outreach visitor,
      questionnaires for the GPs, staff and patients were used to assemble data on the
      number and quality of improvement activities undertaken and on practice
      management prior to the start of the intervention and 1 year later. RESULTS: Pre
      test and post-test data were compared for the 26 intervention and 23 control
      practices. A significant intervention effect was found for the number of
      improvement objectives actually defined (93 versus 54, P<0.001) and successfully
      completed (80 versus 69% of the projects, P<0.001). The intervention group also
      improved on more aspects of practice management, as measured by our practice
      visit method, than the control group but none of these differences proved
      statistically significant. CONCLUSION: The intervention exerted a significant
      effect on the number and quality of improvement projects undertaken and self
      defined objectives met. Failure of the effects of the intervention on the other
      dimensions of practice management to achieve significance may be due to the
      topics selected for some of the improvement projects being only partly covered by
      the assessment instrument.

PMID- 17007711
TI  - Is the promotion of physical activity in vulnerable older people feasible and
      effective in general practice?
AB  - There is convincing evidence about the benefits of exercise training in community
      dwelling frailer older people, but little evidence that this intervention can be
      delivered in general practice. In this prospective cohort study in 14 general
      practices in north London we assessed the feasibility and effectiveness of a
      tailored exercise referral programme for frail elderly patients delivered within
      a variety of inner city primary care settings. One hundred and twenty-six women
      and 32 men aged 75 years and older, deemed borderline frail by their GPs, took
      part in a two-phase progressive exercise programme (Stage 1--primary care
      setting; Stage II--leisure/community centre setting) using the Timed Up And Go
      (TUG) test as the primary outcome measure. Baseline TUG measures confirmed that
      the participants were borderline frail and that GP selection was accurate. Of
      those referred by their GP or practice nurse 89% took up the exercise programme;
      73% completed Stage I and 63% made the transition to the community Stage II
      programme. TUG improved in Stage I with a mean difference of 3.5 seconds
      (P<0.001). An individually tailored progressive exercise programme following GP
      referral, delivered in weekly group sessions by specialist exercise instructors
      within general practices, was effective in achieving participation in exercise
      sessions and in improving TUG values in a significant number of frailer older
      citizens.

PMID- 17007713
TI  - Ever been HAD?

PMID- 17007712
TI  - Henna tattooing dermatitis: consider an additive as the culprit.

PMID- 17007715
TI  - Should I go or should I stay?

PMID- 17007714
TI  - Euthanasia abroad.

PMID- 17007716
TI  - Privatising primary care.

PMID- 17007717
TI  - NICE guidelines on antidepressants.

PMID- 17007718
TI  - Living wills to provide a legal "indication".

PMID- 17007719
TI  - Dangerous CATS and non-barking dogs.

PMID- 17007721
TI  - The future of general practice.

PMID- 17007722
TI  - Do standardised patients lose their confidence in primary medical care? Personal
      experiences of standardised patients with GPs.

PMID- 17007723
TI  - Bodies at the Edinburgh Festival.

PMID- 17007725
TI  - Atraumatic.

PMID- 17007727
TI  - Losing our way.

PMID- 17007728
TI  - The itching, burning eye: diagnostic algorithm and management options.
AB  - The healthy ocular surface is a complex, composite unit that is essential for
      patient comfort and visual function. A number of components need to work in an
      integrated manner to ensure that this is achieved, and a variety of causes can
      result in the final common symptom complex that can be termed the itching,
      burning eye. Many of these causes may be due to relatively common and simple
      issues related to lid disease, allergies, tear dysfunction, excessive computer
      use, exposure to polluted environment, and convergence problems. However, a
      smaller group may have potentially more serious pathology due to causes such as
      underlying immune dysfunction, or tumors; rarely, intraocular conditions and some
      neurological causes may present with ocular redness and grittiness. Failure or
      delay in the diagnosis of these latter entities can result in significant
      morbidity to the eye. This article will clarify issues related to the functioning
      of the ocular surface, provide a diagnostic algorithm for managing these
      patients, and discuss the current knowledge in the management of these conditions
      once they are diagnosed. It is targeted at the practicing ophthalmologist and
      should help him or her to manage this problem effectively.

PMID- 17007730
TI  - Vitreous floaters.
AB  - Floaters are a common presenting ophthalmic symptom that may accompany sight
      threatening disorders. In most cases, they are often secondary to benign,
      degenerative changes in the vitreous. In this review, we briefly examine the
      anatomy of the vitreous and describe how degenerative vitreous change contributes
      to the development of floaters. The causality of floaters in the presence and
      absence of a posterior vitreous detachment is reviewed, as is the clinical
      significance of these symptoms and signs in relation to their predictive value
      for determining the presence of sight-threatening retinal tears and/or
      detachment. Finally, a brief review of management options for debilitating
      floaters is presented.

PMID- 17007731
TI  - Proliferative vitreoretinopathy: developments in pathogenesis and treatment.
AB  - Proliferative vitreoretinopathy is an abnormal wound-healing response following
      retinal detachment and occurs in 5% to 10% of cases. It is now possible to treat
      this once-blinding condition. However, proliferative vitreoretinopathy still
      remains the most common cause of failure to reattach the retina. Recent work has
      helped to unravel the causes of proliferative vitreoretinopathy, and new adjuvant
      treatments are being evaluated to improve the success rate of retinal
      reattachment surgery, both anatomically and functionally. At present,
      preventative treatment has only been found to work in high-risk cases. It is
      hoped that improvement in targeted immunosupression will eventually reduce the
      incidence of proliferative vitreoretinopathy. At the current time, the management
      of proliferative vitreoretinopathy still remains a surgical skill.

PMID- 17007732
TI  - Evaluation and treatment of papilledema in pregnancy.
AB  - Papilledema is defined as optic disk edema that is secondary to increased
      intracranial pressure. During pregnancy, papilledema poses additional diagnostic
      and therapeutic challenges. As in the nonpregnant patient, the primary goal is to
      urgently determine the cause of the papilledema followed by implementing
      appropriate management for life-threatening conditions in a timely fashion while
      safeguarding the fetus. Papilledema may occur also in conditions that are not
      life threatening; in either case, papilledema may cause visual failure. We
      describe the two most common causes of papilledema during pregnancy, idiopathic
      intracranial hypertension and cerebral venous thrombosis. In the former, there is
      no threat to life, while in the latter, depending on the extent of the cerebral
      venous thrombosis, life-threatening medical issues may dominate the picture. In
      these conditions, attention to the prevention of visual failure is of major
      importance; however, treatment options may need to be modified to safeguard the
      developing fetus. In this article, we review the current diagnostic and treatment
      options for patients with papilledema, emphasizing special considerations for the
      pregnant patient, including a chart to help the clinician differentiate between
      the different conditions causing papilledema. A flow chart suggests an approach
      as to how to monitor vision function and steps to take to prevent visual loss in
      these conditions causing papilledema. Drugs that may be considered in the
      management of papilledema are reviewed, and the FDA information regarding their
      safety for the fetus is provided.

PMID- 17007734
TI  - Neuronal nicotinic acetylcholine receptors serve as sensitive targets that
      mediate beta-amyloid neurotoxicity.
AB  - Alzheimer's disease (AD) is the most common form of brain dementia characterized
      by the accumulation of beta-amyloid peptides (Abeta) and loss of forebrain
      cholinergic neurons. Abeta accumulation and aggregation are thought to contribute
      to cholinergic neuronal degeneration, in turn causing learning and memory
      deficits, but the specific targets that mediate Abeta neurotoxicity remain
      elusive. Recently, accumulating lines of evidence have demonstrated that Abeta
      directly modulates the function of neuronal nicotinic acetylcholine receptors
      (nAChRs), which leads to the new hypothesis that neuronal nAChRs may serve as
      important targets that mediate Abeta neurotoxicity. In this review, we summarize
      current studies performed in our laboratory and in others to address the question
      of how Abeta modulates neuronal nAChRs, especially nAChR subunit function.

PMID- 17007735
TI  - Animal models of Huntington's disease: implications in uncovering pathogenic
      mechanisms and developing therapies.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder,
      which is caused by an abnormal expansion of Cytosine Adenine Guanine (CAG)
      trinucleotide repeat in the gene making huntingtin (Htt). Despite intensive
      research efforts devoted to investigate molecular mechanisms of pathogenesis,
      effective therapy for this devastating disease is still not available at present.
      The development of various animal models of HD has offered alternative approaches
      in the study of HD molecular pathology. Many HD models, including chemical
      induced models and genetic models, mimic some aspects of HD symptoms and
      pathology. To date, however, there is no ideal model which replicates all of the
      essential features of neuropathology and progressive motor and cognitive
      impairments of human HD. As a result, our understanding of molecular mechanisms
      of pathogenesis in HD is still limited. A new model is needed in order to uncover
      the pathogenesis and to develop novel therapies for HD. In this review we
      discussed usefulness and limitations of various animal and cellular models of HD
      in uncovering molecular mechanisms of pathogenesis and developing novel therapies
      for HD.

PMID- 17007736
TI  - Traditional Chinese medicine in treatment of opiate addiction.
AB  - Traditional Chinese medicine (TCM) includes Chinese medicine and acupuncture.
      Chinese medicine consists of natural products including plants, animals and
      minerals. TCM has been practiced in China for more than 2000 years, and for the
      past 200 years has been used in treatment of drug addiction. Ten Chinese
      medicines for the treatment of opiate addiction have been approved by the Chinese
      State Food and Drug Administration (SFDA), and at least 6 are in clinical trials.
      The general therapeutic principle of Chinese medicine developed was based on its
      unique theory of " reinforcing healthy Qi and resolving and removing effects of
      toxicity". Acupuncture, another essential part of TCM, which was developed based
      on the principle that " functions of the human body are controlled by the ' Jing
      Luo' and 'Qi-Xue'system" , has been used not only in China, but also in Europe,
      the USA and other countries, for controlling opiate addiction. There are some
      advantages in using TCM for opiate detoxification, including less harmful side
      effects, high safety and ideal effects in the inhibition of protracted withdrawal
      symptoms and relapse. Co-administration of TCM with modern medicine shows some
      synergistic effects in detoxification. Many TCM for detoxification also have
      efficacy in the rehabilitation of abnormal body functions induced by chronic drug
      use, including improving immune function, increasing working memory and
      preventing neurological disorder. Given that TCM is effective in the prevention
      of relapse and causes fewer side effects, it may be used widely in the treatment
      of opiate addiction.

PMID- 17007737
TI  - Effects of sodium ferulate on amyloid-beta-induced MKK3/MKK6-p38 MAPK-Hsp27
      signal pathway and apoptosis in rat hippocampus.
AB  - AIM: To observe the effects of sodium ferulate (SF) on amyloid beta (Abeta)1-40
      induced p38 mitogen-activated protein kinase (MAPK) signal transduction pathway
      and the neuroprotective effects of SF. METHODS: Rats were injected
      intracerebroventricularly with Abeta1-40. Six hours after injection, Western
      blotting was used to determine the expressions of phosphorylated mitogen
      activated protein kinase kinase (MKK) 3/MKK6, phospho-p38 MAPK, interleukin (IL)
      1beta, phospho-MAPK activating protein kinase 2 (MAPKAPK-2), the 27 kDa heat
      shock protein (Hsp27), procaspase-9, -3, and -7 cleavage, and poly (ADP-ribose)
      polymerase (PARP) cleavage. Seven days after injection, Nissl staining was used
      to observe the morphological change in hippocampal CA1 regions. RESULTS:
      Intracerebroventricular injection of Abeta1-40 induced an increase in
      phosphorylated MKK3/MKK6 and p38 MAPK expressions in hippocampal tissue. These
      increases, in combination with enhanced interleukin (IL)-1beta protein expression
      and reduced phospho-MAPKAPK2 and phospho-Hsp27 expression, mediate the Abeta
      induced activation of cell death events as assessed by cleavage of procaspase-9, 
      3, and -7 and caspase-3 substrate PARP cleavage. Pretreatment with SF (100 mg/kg
      and 200 mg/kg daily, 3 weeks) significantly prevented Abeta1-40-induced increases
      in phosphorylated MKK3/MKK6 and p38 MAPK expression. The Abeta1-40-induced
      increase in IL-1beta protein level was attenuated by pretreatment with SF. In
      addition, Abeta1-40-induced decreases in phosphorylated MAPKAPK2 and Hsp27
      expression were abrogated by administration of SF. In parallel with these
      findings, Abeta1-40-induced changes in activation of caspase-9, caspase-7, and
      caspase-3 were inhibited by pretreatment with SF. CONCLUSION: SF prevents Abeta1
      40-induced neurotoxicity through suppression of MKK3/MKK6-p38 MAPK activity and
      IL-1beta expression and upregulation of phospho-Hsp27 expression.

PMID- 17007738
TI  - Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and
      histopathological recovery after experimental spinal cord injury.
AB  - AIM: To investigate the neuroprotective effect of resveratrol in an experimental
      spinal cord injury (SCI) model in rats. METHODS: Male Wistar albino rats weighing
      200-250 g were randomized into six groups. Weight-drop trauma was performed for
      SCI. Group 1 underwent laminectomy alone. Group 2 underwent laminectomy followed
      by SCI. Groups 3, 4, 5, and 6 underwent laminectomy followed by SCI and received
      resveratrol (100 mg/kg), methylprednisolone (MP) (30 mg/kg), resveratrol (100
      mg/kg) plus MP (30 mg/kg), and ethanol (2%), respectively. The rats were divided
      into two subgroups for biochemical analysis (killed at 24 h after surgery) and
      for neurobehavioral and histopathological evaluation (killed at 6 weeks after
      surgery). Posttraumatic neurological recovery after surgery was recorded weekly.
      RESULTS: Groups 3 and 5 revealed significantly lower malon-dialdehyde, nitric
      oxide, xanthine oxidase, and higher glutathione levels than group 4 (P<0.05).
      Neurological recovery rates were significantly better in groups 3 and 5 than
      group 4 (P<0.05). When spinal trauma size ratios were compared, there was no
      significant difference between treatment groups. CONCLUSION: Resveratrol
      treatment revealed better biochemical recovery in the acute stage of trauma than
      MP treatment. Although resveratrol and combined treatment revealed better
      neurobehavioral recovery than MP treatment; resveratrol, MP, and combined
      treatment modalities improved histopathological recovery at the same level in the
      final stage of the experiment. Future studies involving different doses of
      resveratrol and different doses combinations with MP could promise better results
      as each drug has a different anti-oxidative mechanism of action.

PMID- 17007739
TI  - Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion
      of monocytes to smooth muscle cells in vitro.
AB  - AIM: To explore the effects of cariporide on the expression of intercellular
      adhesion molecule-1 (ICAM-1) and the adhesion of monocytes to vascular smooth
      muscle cells (SMC) in vitro. METHODS: Monocytes were isolated from human
      peripheral blood by the Ficoll-Hypaque method. The expression of ICAM-1 in SMC
      was detected by ELISA. The adhesion of monocytes to SMC was stimulated by
      lysophosphatidylcholine (LPC). The adhesion ratio of monocytes was assayed by
      measuring protein contents. The intracellular pH ([pH]i) of SMC was measured with
      2' ,7' -bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF). RESULTS:
      Preincubation of SMC with LPC alone (5 microg/mL) for 4 h markedly enhanced the
      expression of ICAM-1 in SMC and the rate of the adhesion of monocytes to SMC in a
      concentration-dependent and time-related manner. LPC simultaneously also induced
      an increase of [pH]i value in SMC. Cariporide concentration-dependently reduced
      the adhesion ratio of monocytes to SMC and the expression of ICAM-1 in SMC
      induced by LPC. The inhibitory effects of cariporide on the expression of ICAM-1
      in SMC and the adhesion of monocytes to SMC also were associated with blocking
      LPC-induced elevation of the [pH]i value in SMC. CONCLUSION: LPC-induced monocyte
      SMC adhesion may be mediated via activation of the Na+/H+ (NHE) exchanger. The
      action mechanism of cariporide may be related with inhibition of activation of
      the Na+/H+ exchanger of plasma membranes and ICAM-1 expression on the surface of
      SMC induced by LPC.

PMID- 17007740
TI  - Deferiprone protects the isolated atria from cardiotoxicity induced by
      doxorubicin.
AB  - AIM: To investigate the effects of deferiprone on doxorubicin-induced
      cardiotoxicity and determine its protection on cardiac contractility in vivo at
      tissue level. METHODS: Spontaneously-beating isolated atria from rats were
      pretreated with deferiprone for 10 min at 1.2 mmol/L or 0.3 mmol/L, respectively
      before co-incubation with doxorubicin (DOX) at 0.03 mmol/L for 60 min.
      Contractility (dF/dt) was assessed every 10 min during the incubation. After
      that, the tissues around the sinuatrial nodes were fixed for ultrastructural
      study; succinate dehydrogenase (SDH) and Cu, Zn superoxide dismutase (Cu, Zn-SOD)
      activity, as well as malondialdehyde (MDA) level of the atria were assayed.
      RESULTS: Treatment with DOX alone resulted in a 49.34% reduction of the
      contractility, mitochondria swelling, disruption of mitochondrial crista and
      decreased electron density of the matrices. Conversely, with the presence of
      deferiprone, the negative inotropic effect and lesions in the cardiac
      mitochondria structure induced by DOX were attenuated. Cu, Zn-SOD activity
      increased by 12.97%-12.11%, the MDA level decreased by 29.12%-39.82% and
      succinate dehydrogenase (SDH) activity was ameliorated by 25.15%-34.76%.
      CONCLUSION: Deferiprone can efficiently preserve cardiac contractility. Moreover,
      the results of this study indicate that deferiprone is able to protect
      mitochondrial function and structure form damage induced by DOX. This cardiac
      protective potential of deferiprone could be due to its defense capability
      against oxidative damage.

PMID- 17007741
TI  - Calcitonin gene-related peptide inhibits interleukin-1beta-induced interleukin-8
      secretion in human type II alveolar epithelial cells.
AB  - AIM: Our previous data have shown that type II alveolar epithelial (AEII) cells
      express neuropeptide calcitonin gene-related peptide (CGRP), and that pro
      inflammatory factor interleukin1-beta (IL-1beta) induces CGRP secretion in the
      A549 human AEII cell line. In the present study, we investigated the effect of
      endogenous and exogenous CGRP on IL-1beta-induced chemokine interleukin-8 (IL-8)
      secretion. METHODS: We used enzyme-linked immunosorbent assay (ELISA) and RT-PCR
      to detect IL-8 protein and mRNA levels, respectively. siRNA and the stably
      transfected cell line were used to knock down and overexpress the CGRP gene,
      respectively, and chemiluminescence assay was used to detect reactive oxygen
      species (ROS) formation. RESULTS: CGRP-1 receptor antagonist hCGRP8-37 (0.1-1
      nmol/L) greatly amplified IL-1beta-induced IL-8 production. The inhibition of
      CGRP expression by siRNA significantly increased IL-8 secretion upon IL-1beta
      stimulation. However, cell clones stably transfected with CGRP showed
      significantly inhibited mRNA and protein levels of IL-8 induced by IL-1beta.
      CONCLUSION: These data imply that AEII cell-derived CGRP suppress IL-1beta
      induced IL-8 secretion in an autocrine/paracrine mode. Further investigation
      showed that CGRP attenuated IL-1beta-aroused ROS formation, which is an early
      indication of pro-inflammatory factor signaling.

PMID- 17007742
TI  - Antidiabetic effect of a novel non-thiazolidinedione PPAR gamma/alpha agonist on
      ob/ob mice.
AB  - AIM: To study whether T33, a new synthesized non-thiazolidinedione (TZD)
      peroxisome proliferator-activated receptor (PPAR) gamma/alpha dual agonist has an
      antidiabetic effect on ob/ob mice. METHODS: Ob/ob mice were treated with 4 mg/kg
      or 8 mg/kg T33 by gavage for 20 d. Blood glucose levels were measured regularly.
      An oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT) were
      preformed on d 8 and d 12, respectively. The levels of insulin, triglyceride and
      free fatty acid (FFA) in the serum were measured at the end of administration.
      The intramuscular and liver triglyceride content was also determined. RESULTS:
      T33 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia of the ob/ob
      mice. The OGTT and ITT showed that the insulin resistance state of the ob/ob mice
      was obviously ameliorated after T33 treatment. After 20 d treatment with 8 mg/kg
      T33, the triglyceride content in the gastrocnemius muscle decreased
      significantly. T33 did not have any effect on triglyceride content in the liver,
      whereas rosiglitazone significantly increased the hepatocyte lipid deposition.
      CONCLUSION: The PPARgamma/alpha dual agonist T33 has antidiabetic and insulin
      sensitizing effects in ob/ob mice. It has the potential to be a new therapeutic
      candidate for the treatment of type 2 diabetes.

PMID- 17007743
TI  - Translocation of classical PKC and cortical granule exocytosis of human oocyte in
      germinal vesicle and metaphase II stage.
AB  - AIM: Protein kinase C (PKC) is as a family of serine/threonine kinases that can
      be activated by Ca2+, phospholipid and diacylglycerol. PKC plays an important
      role in oocyte maturation and activation. This study was undertaken to
      investigate classical PKC (cPKC) in human oocyte maturation and activation.
      METHODS: Germinal vesicle (GV) and metaphase II (MII) stage oocytes were
      collected from healthy women. The expression and distribution of cPKC were
      investigated by immunoflourescence. MII oocytes were treated with PKC activator
      or inhibitor and imaged using a laser confocal scanning microscope (LCSM).
      RESULTS: In GV oocytes, PKCalpha, beta1 and gamma were localized to the germinal
      vesicles, with a weak expression in ooplasm. In MII oocytes, PKCalpha, beta1 and
      gamma were distributed evenly in ooplasm. After treatment with PKC activator,
      phorbol 12-myristate 13-acetate (PMA), cPKC translocated to the periphery of
      oocyte, and cortical granules (CG) exocytosis was found. When the oocytes were
      treated with PKC inhibitor, staurosporine, no translocation of cPKC and CG
      exocytosis were found. CONCLUSION: PKCalpha, beta1 and gamma exist in human
      oocytes and activation of these subunits could induce CG exocytosis in MII stage.

PMID- 17007744
TI  - Sphingosylphosphorylcholine stimulates human monocyte-derived dendritic cell
      chemotaxis.
AB  - AIM: To investigate the effects of sphingosylphosphorylcholine (SPC) on human
      monocyte-derived dendritic cell (DC) chemotaxis. METHODS: Human DC were generated
      from peripheral blood monocytes by culturing them with granulocyte macrophage
      colony stimulating factor and interleukin-4. The effect of SPC on the DC
      chemotactic migration was measured by chemotaxis assay. Intracellular signaling
      event involved in the SPC-induced DC chemotaxis was investigated with several
      inhibitors for specific kinase. The expression of the SPC receptors was examined
      by reverse transcription polymerase chain reaction. RESULTS: We found that SPC
      induced chemotactic migration in immature DC (iDC) and mature DC (mDC). In terms
      of SPC-induced signaling events, mitogen activated protein kinase activation and
      Akt activation in iDC and mDC were stimulated. SPC-induced chemotaxis was
      mediated by extracellular signal-regulated protein kinase and phosphoino-sitide-3
      kinase, but not by calcium in both iDC and mDC. Although mDC express ovarian
      cancer G protein-coupled receptor 1, but not G protein-coupled receptor 4, iDC do
      not express any of these receptors. To examine the involvement of sphingosine-1
      phosphate (S1P) receptors, we checked the effect of an S1P receptor antagonist
      (VPC23019) on SPC-induced DC chemotaxis. VPC23019 did not affect SPC-induced DC
      chemotaxis. CONCLUSION: The results suggest that SPC may play a role in
      regulating DC trafficking during phagocytosis and the T cell-stimulating phase,
      and the unique SPC receptor, which is different from S1P receptors, is involved
      in SPC-induced chemotaxis.

PMID- 17007745
TI  - Efflux of potassium ion is an important reason of HL-60 cells apoptosis induced
      by tachyplesin.
AB  - AIM: To investigate the role of intercellular potassium in tachyplesin-induced HL
      60 cells apoptosis. METHODS: The concentration of intercellular potassium, cell
      volume and mitochondrial membrane potential were examined by flow cytometry.
      RESULTS: The concentration of intercellular potassium reduced in a time-dependent
      manner in tachyplesin-treated HL-60 cells. In addition, the loss of mitochondrial
      membrane potential was tightly coupled with the shrinkage of cell volume.
      Different caspase inhibitors protected against DNA degradation but did not
      prevent the loss of HL-60 cell viability induced by tachyplesin. Ba2+, which was
      a kind of blocker of volume-regulatory K+ channels, increased the viability of
      tachyplesin-treated HL-60 cells and maintained mitochondrial membrane potential
      and cell volume. CONCLUSION: Efflux of K+ was an important reason for apoptosis
      in tachyplesin-treated HL-60 cells. Efflux of K+ affected the viability of
      tachyplesin-treated HL-60 cells independent of the process of caspase activation.

PMID- 17007746
TI  - Efficacy of sequential treatment of HCT116 colon cancer monolayers and xenografts
      with docetaxel, flavopiridol, and 5-fluorouracil.
AB  - AIM: Clinical treatment of solid tumors with docetaxel, flavopiridol, or 5
      fluorouracil (5-FU) often encounters undesirable side effects and drug
      resistance. This study aims to evaluate the potential role of combination therapy
      with docetaxel, flavopiridol, or 5-FU in modulating chemosensitivity and better
      understand how they might be used clinically. METHODS: HCT116 colon cancer cells
      were treated with docetaxel, flavopiridol, and 5-FU in several different
      administrative schedules in vitro, either sequentially or simultaneously. Cell
      survival was measured by MTT assay. The activity of caspase-3 was determined by
      caspase-3 assays and the soft agar colony assay was used to test the colony
      formation of HCT116 cells in soft agar. We also established xenograft models to
      extend in vitro observations to an in vivo system. RESULTS: The maximum
      cytotoxicity was found when human colon cancer HCT116 cells were treated with
      docetaxel for 1 h followed by flavopiridol for 24 h and 5-FU for another 24 h.
      This sequential combination therapy not only inhibits tumor cell growth more
      strongly compared to other combination therapies but also significantly reduces
      colony formation in soft agar and augments apoptosis of HCT116 cells. Sequencing
      of docetaxel followed 1 h later by flavopiridol, followed 24 h later by 5-FU in
      xenograft models, also resulted in delayed tumor growth and higher survival rate.
      CONCLUSION: These results highlight the importance of an administrative schedule
      when combining docetaxel with flavopiridol and 5-FU, providing a rationale
      explanation for its development in clinical trials.

PMID- 17007747
TI  - In vitro and in vivo evaluation of a novel oral insulin formulation.
AB  - AIM: To develop a stable self-emulsifying formulation for oral delivery of
      insulin. METHODS: Caco-2 cell line and diabetic beagles were used as in vitro and
      in vivo models to study the absorption mechanism and the hypoglycemic efficacy of
      the formulation. In addition, various physicochemical parameters of the
      formulation such as droplet size, insulin encapsulation efficiency and stability
      were evaluated. RESULTS: This formulation enabled changes in barrier properties
      of Caco-2 monolayers, as referred by transepithelial electrical resistance (TEER)
      and apparent permeability coefficients (P(app)) of the paracellular marker
      ranitidine (20-fold greater than control) but not transcellular marker
      propranolol, suggesting that the opening of tight junctions was involved. In
      diabetic beagle dogs, the bioavailability of this formulation was up to 15.2% at
      a dose of 2.5 IU/kg in comparison with the hypoglycemic effect of native insulin
      (0.5 IU/kg) delivered by subcutaneous injection. CONCLUSION: This formulation,
      recently approved by the China State Food and Drug Administration to enter
      clinical trials, was stable, degradation-protected and absorption-enhanced, and
      provided a promising formulation for oral insulin delivery.

PMID- 17007748
TI  - HIV/AIDS threat in Pakistan: changing concerns and realities.

PMID- 17007749
TI  - Thyroid function in pulmonary tuberculosis.
AB  - OBJECTIVE: To evaluate the thyroid hormone economy in pulmonary tuberculosis
      (PTB). DESIGN: Cohort comparative study. PLACE AND DURATION OF STUDY: Multan
      Institute of Radiotherapy and Nuclear Medicine (MINAR) from January 2003 to June
      2005. PATIENTS AND METHODS: The study included 266 confirmed cases of pulmonary
      tuberculosis (PTB), aged between 11 and 65 years, who had completed short course
      of chemotherapy. Two samples were collected from each patient, first after final
      diagnosis and second after completion of the treatment. Initial analysis of
      samples showed that 31 samples had both T3 (triiodothyronine) and T4 (thyroxine)
      in lower than normal range. One more sample in the middle of treatment was
      collected for these patients. Radioimmunoassays and immunoradiometeric assays
      were applied to estimate mean TT3, TT4 and TSH (thyroid stimulating hormone)
      levels. Students t-test was used to compare patient and normal values derived
      from 713 volunteers. RESULTS: The age had no effect on levels of T3, T4 and TSH
      in normal persons. Mean T3 and T4 values (0.74 nmol/l and 91.9 nmol/l) in PTB
      patients were significantly decreased (p < 0.001) with 50% and 11.6 % cases in
      lower than normal range respectively. Follow-up data on subgroup of 31 patients
      showed that both T3 and T4 levels improved after chemotherapy. TSH levels
      remained unaffected throughout. CONCLUSION: Both T3 and T4 levels were decreased
      in PTB but T4 levels were less affected. TSH was found unaffected by the disease.
      This confirms that PTB produces euthyroid sick syndrome (SES) i.e., decreased T3
      and T4, and no change affected by 5'deiodinase (an enzyme that causes
      deiodination of T4). The levels improved after chemotherapy.

PMID- 17007750
TI  - Antioxidant markers in human senile and diabetic cataractous lenses.
AB  - OBJECTIVE: To determine the role of free radicals and antioxidant enzymes in
      patients suffering from cataract due to aging and diabetes. DESIGN: Experimental
      study. PLACE AND DURATION OF STUDY: Department of Biochemistry, University of
      Karachi from December 2004 to May 2005. PATIENTS AND METHODS: The study was
      conducted on 80 cataract patients. Lens and plasma samples from senile and
      diabetic subjects suffering from cataract were analyzed and activity of Cu, Zn
      superoxide dismutase (Cu, Zn-SOD) was measured using xanthine oxidase system.
      Catalase (CAT) activity was estimated. Levels of malondialdehyde (MDA) was
      measured by thiobarbituric acid reaction. Student's t- test was employed for
      analysis of results. RESULTS: Significant difference (p<0.001) was found in
      activity of Cu, Zn-SOD in cataract lenses from diabetic patients as compared to
      senile subjects, CAT activities was also lower (p<0.001) in lenses from diabetic
      cataract patients when compared to lenses from senile cataractous subjects. Lens
      MDA levels were significantly higher (p<0.001) in cataract lenses from diabetic
      patients than in senile subjects. Plasma MDA levels were lowest (p<0.001) in
      controls as compared to senile and diabetic cataractous patients. CONCLUSION:
      Results of present study suggest that increased production of high levels of free
      oxygen species is linked to glucose oxidation and non-enzymatic glycation of
      proteins. Furthermore, elevated glucose levels might be involved in the
      insufficiency of antioxidant enzymatic activity and in the progression of lipid
      peroxidation.

PMID- 17007751
TI  - Comparison of plain potassium hydroxide mounts, fungal cultures and nail plate
      biopsies in the diagnosis of onychomycosis.
AB  - OBJECTIVE: To compare the relative sensitivity of direct microscopy, fungal
      culture and nail plate biopsy in the diagnosis of onychomycosis. DESIGN: Cross
      sectional study. PLACE AND DURATION OF STUDY: The Skin Department, Military
      Hospital, Rawalpindi from February 1998 to February 1999. PATIENTS AND METHODS: A
      total of 50 patients who were suffering from different clinical variants of
      onychomycosis, irrespective of their age, gender, with or without simultaneous
      presence of systemic diseases, were subjected to laboratory investigations
      including direct microscopy with 20% potassium hydroxide (KOH) for fungal hyphae,
      fungal cultures and nail plate biopsies. These patients were later categorized
      into two groups based upon the results of nail plate biopsies. RESULTS: Of 50
      patients, 15 (30%) were positive for fungal elements in direct microscopy, 8
      (16%) were positive for fungal culture and 16 (32%) revealed positive results in
      nail plate biopsies. Amongst nail plate biopsy positive cases, 10 (63%) were
      positive for direct microscopy and 6 (37.5%) were positive for fungal cultures.
      In biopsy negative cases, positive results for direct microscopy were seen in 5
      (14.7%) patients and positive fungal culture was found in 2 (5.88%) patients.
      CONCLUSION: The clinical impression of onychomycosis is not true in all the
      cases. Nail scraping for direct microscopy with 20% KOH should be the first line
      screening test for all patients which should then be supplemented with fungal
      culture and/ or nail plate biopsy.

PMID- 17007752
TI  - Pattern of visceral injuries following blunt abdominal trauma in motor vehicular
      accidents.
AB  - OBJECTIVE: To determine the frequency of various visceral injuries following,
      high-speed motor vehicle crashes with special reference to frequency of liver
      injuries, severity and complications. DESIGN: A descriptive study. PLACE AND
      DURATION OF STUDY: Surgical Unit III, Jinnah Hospital, Lahore, from August 1999
      to February 2002. PATIENTS AND METHODS: The study included 100 consecutive
      patients of blunt abdominal trauma. Patients of either gender and age above 12
      and below 70 were included in this study. Purposive non-probability sampling was
      done. Injuries were identified, graded and managed accordingly. The data was then
      entered into SPSS and descriptive statistical tests were applied. RESULTS: Liver
      was the most common organ injured (35%), followed by spleen (32 %) and small gut
      (30 %). In 23 patients, liver was the only organ injured. Most of the liver
      injuries fell under grade I (42.8%) followed by grade II (28.35%) and grade III
      (22.85%) and were treated by suture hepatorrhaphy alone in 71.42% cases. The
      operated cases were mostly complicated by wound infection (33.76%). Overall
      mortality remained high (12%) and was related to a combination of delays in
      arriving at a diagnosis due to non-availability of CT scan and routine use of
      peritoneal lavage. CONCLUSION: Liver is the most commonly affected organ in high
      speed motor vehicle crashes that is reliably treated by suture hepatorrhaphy. The
      rate of postoperative infection and morbidity is high.

PMID- 17007753
TI  - Maternal morbidity and mortality associated with delivery after intrauterine
      fetal death.
AB  - OBJECTIVE: To determine the maternal morbidity and mortality associated with
      delivery after intrauterine fetal death (IUFD) and to find out the place of fetal
      destructive procedures and cesarean section. DESIGN: Cross-sectional study. PLACE
      AND DURATION OF STUDY: Labour Room, Nishtar Hospital, Multan from January to
      December 2003. PATIENTS AND METHODS: All women were included in the present study
      who presented before the onset of labour pains, after intrauterine fetal death at
      26 weeks or onward with singleton pregnancy. Assessment of maternal demographic
      characteristics, gestational age at fetal demise, delivery-IUFD interval, mode of
      delivery; vaginal with or without fetal destructive procedures/cesarean section
      and maternal complications were the main outcome measures. RESULTS: There were
      1834 live birth and 63 deliveries with intrauterine fetal death. Mode of delivery
      was vaginal in 87.4% and cesarean section in 12.6% of the cases. Twelve (21%) of
      the vaginal deliveries were complicated by lower urogenital tract injuries in
      certain cases, whereas 75% (6/8) of patients delivered by cesarean section
      developed major postoperative complications like postpartum haemorrhage, shock,
      endometritis, peritonitis and wound dehiscence. No maternal death was identified.
      Rate of delivery with intrauterine fetal death was 34.3/1000 live-birth
      deliveries. CONCLUSION: Maternal morbidity like perineal tear, urinary tract
      infection, menstrual disorder and even secondary infertility may follow after
      vaginal mode of delivery by forceps and destructive procedures. The frequency and
      severity of complications after cesarean delivery are quite higher and may rarely
      lead to even maternal death.

PMID- 17007754
TI  - Cosmetic outcome of three sutures levator aponeurosis tuck procedure in
      congenital ptosis.
AB  - OBJECTIVE: To determine the results of three sutures aponeurosis tuck procedure
      in patients with congenital ptosis. DESIGN: A quasi-experimental study. PLACE AND
      DURATION OF STUDY: Department of Ophthalmology, Khyber Teaching Hospital,
      Peshawar from January 2004 to January 2005. PATIENTS AND METHODS: Twenty-four
      eyes of 20 patients (13 males and 7 females) with congenital ptosis were included
      in the study. All these lids had either good or fair levator function. Amount of
      ptosis in all lids were measured before surgery and their mean calculated. Single
      surgeon performed the three sutures levator aponeurosis tuck procedure on all
      these lids. Degree of ptosis, after surgery was measured on multiple occasions
      and mean of measures of last follow-up was calculated. At this stage, the
      patients' satisfaction level was also documented. RESULTS: Mean amount of ptosis
      was 3.25 +/-0.99 mm before surgery and 0.33 +/- 0.56 mm after surgery (p <
      0.0001). Satisfaction level of 18 (90%) patients was 70-90%, while in 2 (10%)
      patients it was 50-60%. CONCLUSION: Levator aponeurosis tuck procedure had good
      cosmetic outcome in patients with congenital ptosis having good and fair levator
      function in this series.

PMID- 17007755
TI  - Mortality and morbidity in elderly patients with fracture neck of femur treated
      by hemiarthroplasty.
AB  - OBJECTIVE: To determine mortality and morbidity in elderly patients with fracture
      neck of femur treated by hemiarthroplasty (Austin Moore Prosthesis) during one
      year postoperatively. STUDY DESIGN: Descriptive, analytical study. PLACE AND
      DURATION OF STUDY: Department of Orthopaedics, Postgraduate Medical
      Institute/Hayatabad Medical Complex, Peshawar, from June 2001 to May 2002.
      PATIENTS AND METHODS: During the study period, all patients with fracture neck of
      femur, who were 65 years of age or above and treated by Austin Moore Prosthesis
      (AMP), were included. The patients were followed for one year at intervals of 2
      weeks, 4 weeks, 6 months, and one year. All surviving patients were assessed for
      complications, both general and mechanical, related to the implant. The mortality
      and morbidity were compared for various age subgroups, and in patients with and
      without systemic co-morbidities.Chi square test was applied to see the
      significance of results. RESULTS: The total number of patients was 46 with
      average age of 70 years. Male to female ratio was 1:2. There were 70% patients
      who had one or more associated systemic disease. The mortality at 2 weeks was
      4.3%, 17.4% at 6 months and 26% at one year. The overall dislocation rate was
      4.3%. Two patients had infection and 17.4% patients had thigh pain at one year.
      The mortality and morbidity was high in patients with systemic co-morbidities,
      and those above 70 years of age, but this was statistically not significant (p
      value >0.05). The functional assessment of surviving patients at one year was
      graded as excellent or good in 76.4% of patients. CONCLUSION: In this series,
      Austin Moore Prosthesis in elderly patients was associated with dislocation,
      infection and thigh pain in short-term follow-up. The postoperative mortality was
      high, but it was age and systemic co-morbidity-related rather than due to the
      surgical procedure. The functional assessment of hip at one year was excellent or
      good in majority of surviving patients.

PMID- 17007756
TI  - Hearing improvement after stapedotomy using teflon loop prosthesis.
AB  - OBJECTIVE: To assess hearing improvement after stapedotomy for otosclerosis using
      teflon loop prosthesis. DESIGN: Quasy experimental study. PLACE AND DURATION OF
      STUDY: January 2001 to May 2003 in the Otorhinolaryngology Department, CMH,
      Rawalpindi. PATIENTS AND METHODS: Thirty diagnosed cases of otosclerosis were
      included in the study. Ear with greater air-bone gap was selected and stapedotomy
      was done using teflon loop prosthesis (size 4 - 4.5 mm). Mild vertigo occurred
      during immediate postoperative period, which subsided with Inj. Prochlorperazine.
      Patients were followed-up postsurgically at one month, two months, four months,
      six months and one year and postoperative air-bone gap was calculated. RESULTS:
      Out of 30 cases, there were 24 males and 06 females. The age ranged from 18 to 50
      years. Twenty-one (70%) patients had bilateral hearing loss and 09 (30%) had
      tinnitis also. Pre-operative audiograms showed conductive deafness. Carhart's
      notch was present in 10 (33.3%) cases. Tympanogram revealed loss of stapedial
      reflex. Postoperatively good hearing improvement was seen in 56.7% (postoperative
      air-bone gap closure upto 10 dB), fair improvement in 30% (postoperative air bone
      gap closure from 11 to 20 dB) and poor results in 10% (postoperative air-bone gap
      more than 21 dB) cases. One patient developed dead ear. CONCLUSION: Stapedotomy
      using teflon loop prosthesis for otosclerosis is an effective method to restore
      hearing. Complications are uncommon.

PMID- 17007757
TI  - Corticosteroids therapy in the management of infantile cutaneous hemangiomas.
AB  - OBJECTIVE: To determine the effectiveness of systemic and intra-lesional
      corticosteroids, in the management of infantile cutaneous hemangiomas and to
      compare the results with untreated lesions. DESIGN: Randomized controlled trial.
      PLACE AND DURATION OF STUDY: Surgical Unit B of National Institute of Child
      Health, Karachi, from January 2001 to January 2003. PATIENTS AND METHODS: A total
      of 75 cases with cutaneous hemangiomas were included in the study. Three groups
      of 25 patients each were made by allocating first patient to control group, every
      second patient to oral steroid group and every third patient to intra-lesional
      steroid group. In control group, patients were managed conservatively with
      repeated hospital visits in order to note down changes occurring in the lesion.
      In oral steroid group, tablet prednisolone was given at a dose of 2mg/kg/day on
      alternate days. The dose was gradually tapered over a period of 8 weeks. In intra
      lesional steroid group, injection triamcinolone was given at a dose of 1 to 5
      mg/kg, with a maximum dose of 30mg. Six injections of triamcinolone in monthly
      intervals were given. Outcome measures noted were the change in size before and
      after treatment, duration of proliferative phase, change in morphology and
      complications. RESULTS: In the control group,76% lesions showed little or no
      change, 5.8% had less than 50% reduction and 20% lesions showed actual increase
      in size. In oral steroid group, 32% lesions showed greater than 50% reduction in
      size, 44% lesions had less than 50% reduction and 24% lesions had little or no
      change. In intra-lesional steroid group, 44% lesions showed greater than 50%
      reduction in size, 32% lesions showed less than 50% reduction and 24% lesions had
      little or no change. Morphology change in terms of color change, surface
      bosselation and soft consistency was found in 88% lesions of oral steroid group,
      92% in intra-lesional steroid group and 16% in observation group. Complication
      rate was 16% in observation group, 20% in oral steroid group and 24% in intra
      lesional steroid group. CONCLUSION: Hemangiomas when left untreated behave in an
      unpredictable manner. Low dose steroids whether given orally or intra-lesionally,
      showed remarkable reduction in size with minimal side effects.

PMID- 17007758
TI  - Superior mesenteric artery syndrome: an uncommon cause of upper intestinal
      obstruction.
AB  - A previously healthy young boy who was operated for upper gastrointestinal
      obstruction, 12 weeks earlier, without relief of his symptoms of projectile
      bilious emesis and colicky pain, is described. He underwent upper
      gastrointestinal contrast studies, suggesting duodenal obstruction at its third
      part and superior mesenteric artery syndrome, which was confirmed by selective
      superior mesenteric arteriography. Duodenojejunostomy was carried out. The
      patient was symptom-free with normal built and growth after 4 years of follow-up.

PMID- 17007759
TI  - Adenoid cystic carcinoma of larynx.
AB  - This case report presents the clinical picture, diagnostic methodology, and
      surgical treatment of a 30 years old female patient, who presented with
      hoarseness of voice and difficulty in breathing. Direct laryngoscopy showed mass
      in right side of subglottic region, and biopsy-proven adenoid cystic carcinoma.
      Total laryngectomy was performed and patient was discharged three weeks
      postoperatively and doing well.

PMID- 17007760
TI  - Submandibular duct sialolithiasis : an unusual presentation.
AB  - Multiple calculi in a submandibular gland duct is an uncommon occurrence. One
      such case occurring in a young boy of 25 years is reported here where thirteen
      very small stones of 1-3 mm of maximum diameter were lined up in the Wharton's
      duct in such a way that they were difficult to appreciate on inspection and
      palpation. Successful exploration was done in two steps.

PMID- 17007761
TI  - Progressive familial intrahepatic cholestasis.
AB  - Progressive familial intrahepatic cholestasis (PFIC) is an important cause of
      cholestatic liver disease and biliary cirrhosis in pediatric population. Three
      cases of PFIC are described that were diagnosed on the basis of family history,
      pruritus, cirrhosis and / or paucity of interlobular bile ducts on liver biopsy
      and presence of extrahepatic biliary tree on imaging. These patients were
      initially labeled as suffering from extra-hepatic biliary atresia and neonatal
      hepatitis. PFIC-1 and 2 could not be differentiated on histological grounds,
      since these patients presented late and process of fibrosis was advanced.

PMID- 17007762
TI  - Developing a surveillance system for HIV/AIDS in Pakistan.
AB  - Apart from other interventions, surveillance remains a major focus of the
      national response to HIV/AIDS. However, with a shift in the epidemic pattern, the
      existing surveillance strategies are barely insufficient and long-term structural
      changes are desirable. This article provides a conceptual framework for
      developing a scientific system for HIV surveillance in Pakistan. Second
      generation surveillance system including repeated cross-sectional surveys in high
      risk population groups are suggested to collect behavioral and serological data
      at regular intervals on an annual basis to monitor the epidemic trend as well as
      the associated behaviors. In addition, multiple data resources have been
      highlighted, which could be coordinated to describe the epidemic pattern in the
      country. This information should form the basis for national prevention planning
      and ought to be used for making sensible choices through which prevention efforts
      are most likely to reduce new infections.

PMID- 17007763
TI  - Initial diagnostic categories of patients presenting to four major emergency
      departments in Karachi.

PMID- 17007764
TI  - Acute pancreatitis due to hypertriglyceridemia.

PMID- 17007765
TI  - Medical system: need for appraisal and suggestions.

PMID- 17007767
TI  - The denaturation maxima of proteins and of drug-biomolecule complex formation in
      a wide range of methanol/water mixtures. Solvophobic theory predictions as
      compared to experiments.
AB  - Independent experiments have shown that both protein folding (G. Velicelebi and
      J.M. Sturtevant, Biochemistry 18 (1979) 1180) and drug-biomolecule complexation
      (D.M. Crothers and D.I. Ratner, Biochemistry 7 (1968) 1823) in a wide range of
      compositions of methanol/water mixed solvents exhibit a maximum at 8% (v/v) MeOH.
      This hitherto unexplained phenomenon is shown to be given a priori by the
      'solvophobic theory' developed earlier by Sinanoglu which had related the solvent
      effects including water in biochemistry to the then introduced 'molecular surface
      areas' and to 'microthermodynamic cavity inner surface tensions' and in a
      different version to interfacial microtensions between side chains and the
      solvent. Both analyses carried out in the present paper in detail for MeOH/water
      mixtures show how the denaturation or complexation free energies are predicted
      for the entire range of MeOH/water compositions from only data at one point. The
      molecular surface area changes for the conformational processes are obtained as
      well as the free energies in the hypothetical but theoretically important in
      vacuo limits with no solvent present.

PMID- 17007768
TI  - Denaturation of proteins in methanol/water mixtures.
AB  - The solvophobic theory developed earlier by Sinanoglu introducing the use of
      molecular surface areas and microthermodynamic surface and interfacial tensions
      at molecular dimensions is applied to the interpretation of calorimetric data on
      denaturation of lysozyme in a wide range of methanol/water mixtures. The
      experimental values of standard unitary free energies of denaturation correlate
      well with our predictions. The molecular surface area change of the protein upon
      denaturation is evaluated using the solvophobic theory. The maximum in the
      stability of the native form of the protein is predicted to occur at 8% (v/v)
      methanol. This is found to be in agreement with the experimental results.

PMID- 17007769
TI  - Solvophobic forces and molecular surface area changes in drug-biomolecule
      associations as with actinomycin-deoxyguanosine in a wide range of methanol/water
      mixtures.
AB  - A method is given to predict the unitary free energies of complexation between
      drug-like and nucleoside-like biomolecules in a range of mixed solvent
      compositions. A stability maximum for the actinomycin (A)-deoxyguanosine (D)
      complex at 8% MeOH (v/v) in methanol/water mixtures is correctly predicted by the
      theory in agreement with existing experimental data. The molecular surface areas
      of A and D exposed to the solvent are found to diminish by 36.4 A(2) upon
      association. The 'microthermodynamic differential surface tension' of the
      solvophobic theory obtained for nucleoside-like and organic molecules in contact
      with MeOH/H2O can be used to predict the solvent effect free energies in other
      such molecular or biopolymeric associations in solution.

PMID- 17007770
TI  - The influence of diffusion on the rate of a reversible quasi-unimolecular
      reaction in one, two or three dimensions.
AB  - The role of diffusion in the kinetics of a reversible quasi-unimolecular reaction
      is considered. Equations that couple diffusion and reversible reaction are
      defined. From these equations are derived expressions for the concentrations of
      the reacting species, as a function of time, after a perturbation from their
      equilibrium concentrations. These expressions demonstrate how the time-dependent
      approach by a concentration to its equilibrium value is determined by the binding
      rate of adjacent molecules, the dissociation rate, the diffusion coefficients,
      the distance of closest approach of the reactants, the concentrations of the
      reactants, and the dimensionality. The expressions are applicable to perturbation
      relaxation experiments in one, two, and three dimensions. The formalism is
      compared with previously existing theories.

PMID- 17007771
TI  - Derivation of rate equations for a theoretical model for the proposed kinetic
      pathway for regulation of LDL receptor metabolism in fibroblast cells.

PMID- 17007772
TI  - Variation of the shuttling constants for recycling receptors.

PMID- 17007773
TI  - Channel structures in synthetic polypeptides with alternating configurations.
      Conformational analysis of poly(DL-proline).
AB  - Theoretical conformational analysis of L,D alternating sequences of poly alpha
      amino acids is reported in connection with the ability of naturally occurring
      peptide and depsipeptide having alternating configurations to increase
      selectively the ion permeability across membranes. The most stable structures of
      poly(DL-proline), of which the conformational variability is practically limited
      to the choice between cis and trans conformations of the peptide bonds, were
      characterized. The all-trans conformation results in a flat helical structure
      possessing the main features for acting as an ion channel across membranes as
      actually found experimentally. Random cis-trans conformational sequences provide
      an alternative mechanism of ion transport intermediate between the ion channel
      and the ion carrier.

PMID- 17007774
TI  - Aggregation of chlorophylls in monolayers. VI. Infrared study of the CH
      stretching bands of chlorophyll a and of chlorophyll b in monolayers.
AB  - The CH vibrational stretch bands of chlorophyll (Chl) in monolayers, obtained by
      the Langmuir-Blodgett technique have been studied by infrared spectroscopy.
      Compared to a solution or to a multilayer which shows three to four bands, the
      spectra of Chl a or Chl b molecules in monolayers have revealed more than seven
      bands, which are assigned to the various CH groups in the molecule. In contrast
      to solutions or to multilayer samples which give featureless bands, each band of
      the monolayers is composed of many components which are modified when the system
      is perturbed either by drying or by hydration techniques. The separation between
      the components of the CH aliphatic bands is typical of crystalline field
      splitting and the modification of the intensities of these components is
      associated with the movement of the phytyl chain of the chlorophyll molecules.
      The CH aromatic stretch bands have been observed; the displacement and variation
      of the intensities of these bands are associated with deformation of the
      porphyrin ring. The CH band of the formyl group on Chl b has also been observed.
      The displacement and variation of the intensity of this band are related to the
      association that this group makes with the surrounding molecules and with the
      displacement of the porphyrin ring.

PMID- 17007775
TI  - Polarizability of the ionic cloud around a charged membrane sheet.
AB  - The polarizability of the ionic cloud around a charged membrane sheet parallel to
      the surface is calculated. The membrane is modeled as an infinitely thin and long
      strip of width 2d'. The Poisson-Boltzmann equation is solved with an external
      electric field as a perturbation. The polarizability is given in closed integral
      form, with numerical results. At higher salt concentration the polarizability
      varies approximately as kappa(-3), where kappa is the Debye-Huckel constant. The
      given theoretical result can account for the a.c. electrodichroism of purple
      membrane suspensions.

PMID- 17007776
TI  - Band structure of surface electric potential in growing roots.
AB  - For growing roots of azuki bean (Phaseolus chrysanthos), an electric potential is
      measured minutely along the surface of the root, together with the surface pH. It
      was found that the root begins to display a band-type pattern of potential with a
      spatial period of about 2 cm in a mature region as soon as it grows to about 10
      cm in root length, while the surface potential shows only one convex peak around
      a position 5-20 mm behind a root tip and a succeeding concave peak around 20-35
      mm, providing the length of root is shorter than about 10 cm. Since the surface
      potential takes a relatively positive value on average at the side of the root
      base compared with that in an elongation zone near the tip, electric current is
      supposed to flow into the elongation zone, accompanied by some local current
      loops in the mature region. The present band-type pattern observed first in multi
      cell systems seems to be a kind of dissipative structure appearing far from
      equilibrium, and hence its relationship to growth is discussed.

PMID- 17007777
TI  - Dynamic property of membrane formation in a protoplasmic droplet of Nitella.
AB  - A theory is presented to explain the dynamic characteristics of an electric
      potential and the resistance of a surface membrane during the formation of a
      protoplasmic droplet isolated from Nitella. Basic equations are coupled ones for
      describing ion concentrations near the surface of the droplet, active and passive
      ion fluxes on the surface, and kinetics of membrane-constituting molecules
      diffusing from the inside of the protoplasm. The present results give a good
      explanation of the observed kinetics of electric properties throughout the
      formative process of surface membranes after the ion concentrations are replaced
      by lower ones. The results can also explain well the observed data on the steady
      state. Oscillatory changes in the membrane potential induced by ions strongly
      adsorbed on the surface membrane are discussed in relation to growth and
      regeneration phenomena in biological systems such as bean roots and Acetabularia.

PMID- 17007778
TI  - A time-resolved fluorescence study of 4',6'-diamidine-2-phenylindole
      dihydrochloride binding to polynucleotides.
AB  - At phosphate/dye (P/D) ratios greater than 30 the quantum yield of 4',6'
      diamidine-2-phenylindole dihydrochloride (DAPI)-DNA and DAPI-poly(d(A-T))
      complexes was found to be 0.62 and 0.66, respectively. Contrary to earlier
      reports a fluorescence enhancement of DAPI-poly(d(G-C)) complexes was observed
      with a quantum yield of 0.22. Time-resolved fluorescence measurements of
      complexes with a P/D ratio of 150:1 indicate that there were three fluorescent
      components in DAPI-DNA complexes with lifetimes of 3.86, 1.79 and 0.13 ns. In
      DAPI-poly(d(A-T)) complexes the lifetimes were 3.91, 1.20 and 0.11 ns. Also,
      three components with lifetimes of 3.98, 0.87 and 0.12 ns were found in DAPI
      poly(d(G-C)) complexes. At low P/D ratios (< 5) another binding form of DAPI was
      observed which was assigned to the interaction of one or more molecules of DAPI
      with one previously bound to DNA. It is concluded that DAPI does not exhibit A-T
      binding specificity and that at high P/D ratios there are two types of binding
      having similar binding constants.

PMID- 17007779
TI  - Thermotropic properties of bipolar lipids of Sulfolobus solfataricus and of their
      mixtures with dipalmitoylphosphatidylcholine.
AB  - The thermotropic properties of the bipolar lipids, glycerol dialkylglycerol
      tetraether (GDGT) and glycerol dialkylnonitol tetraether (GDNT), were determined
      at different degrees of hydration and in mixtures with
      dipalmitoylphosphatidylcholine (DPPC). The number of water molecules rendered
      unfreezable by the GDNT molecule is 10+/-1.5 and that by the GDGT molecule 2.8+/
      0.7 or about 1.1-1.5 H2O molecules per OH group. Binding of water molecules
      causes randomization of the two polar heads from the oriented form prevailing in
      the dry state. The hydration seems to be a cooperative process extending over a
      whole lipid domain. DPPC added in small amounts to GDNT interacts preferentially
      with the nonitol halves of the molecules separating them from the glycerol half
      molecules. In the cooperative interaction domain each DPPC molecule is surrounded
      by up to six GDNT molecules. Cooperative domains formed during the interaction of
      DPPC with GDGT are less pronounced. In both cases they affect the thermotropic
      properties of the system.

PMID- 17007780
TI  - A multicomponent self-diffusion NMR study of aggregation of nucleotides,
      nucleosides, nucleic acid bases and some derivatives in aqueous solution with
      divalent metal ions added.
AB  - The self-aggregation of the mononucleotides AMP, CMP, and UMP with Mg2+ added
      (nucleotide concentration = Mg2+ concentration) up to 0.4 molal or to their
      solubility limit in 2H2O has been monitored through self-diffusion measurements,
      using the Fourier transform NMR pulsed-gradient spin-echo multicomponent-self
      diffusion technique. Also, purine, cytidine, uridine, purine with Mg2+ added and
      both cytidine and uridine with Mg2+, Zn2+ or Cd2+ added, were studied in the same
      way. The experimental data were fitted to two different aggregation models. For
      the mononucleotides with Mg2+ added a cooperative indefinite aggregation model,
      where the first (dimerization) aggregation constant is a magnitude lower than
      those for the higher aggregation step gives the best agreement between
      simulations and experiment. Typical values are 0.3 and 12 kg mol(-1),
      respectively. The latter value is about twice that found for the uncomplexed
      nucleotides. Also, purine and the nucleosides, cytidine and uridine, with
      divalent metal ions added fit best with this model. The degree of aggregation is
      increased upon metal ion addition, as previously shown for the mononucleotides.
      For purine, cytidine and uridine without metal ions added an 'isodesmic',
      indefinite aggregation model, with the aggregation constant for each step equal,
      fits the data as well. Here the application of the 'semi-isodesmic' model results
      in a higher first (dimerization) aggregation constant than is found for the
      nucleotides. The typical value is 2 kg mol(-1). In this case, the evaluated
      aggregation constants for the higher step become only about twice as large as
      those of the first step. The same measurements on isopropylcytidine,
      isopropyluridine and theophylline-7-acetic acid in water show that these three
      compounds aggregate to the same extent as the nucleosides, cytidine and uridine.
      Pyrimidine diffusion data reveal no aggregation at all; the application of either
      model results in essentially zero aggregation constants.

PMID- 17007781
TI  - Conformational and dynamic features of cocaine in DMSO-d6 solution.
AB  - 13C spin-lattice relaxation rates, 13C {1H} NOESs, 1H spin-spin relaxation rates
      and 1H two-dimensional magnetization transfer spectroscopy were used for
      delineating conformational features of cocaine in DMSO-d6 solution. Two main
      conformations differing in the orientation of the plane made by the benzoxy
      substituent with respect to the piperidine ring principal axis were observed.
      Relatively slow interconversions of the piperidine ring were delineated together
      with the main motional features of the whole molecule.

PMID- 17007782
TI  - Selective 1H-NMR relaxation investigations of membrane-bound drugs in vitro. 1.
      Colchicine.
AB  - Binding of colchicine to dipalmitoylphosphatidylcholine bilayer vesicles was
      detected by measuring the 1H-NMR selective spin-lattice relaxation rates of the
      low-field protons of colchicine. From the temperature dependence of the selective
      rates, preferential binding was observed above the temperature of transition. In
      the same way, binding of colchicine to red blood cells was detected and the
      equilibrium constant determined. Binding to the lipid matrix of red blood cells
      accounted only partially for the binding of colchicine to whole cells.

PMID- 17007783
TI  - Excluded-volume effect of inert macromolecules on the melting of nucleic acids.
AB  - It is shown on the basis of the excluded-volume effect that inert macromolecules
      may be expected to suppress the dissociation of double-helical nucleic acids into
      single helices and thus to raise the melting point of the double helix. The rise
      in melting temperature of the ribonucleic acid [poly(I).poly(C)] caused by
      dextran polymers and by poly(ethylene oxide) is described and compared with the
      theoretical prediction. Good agreement was found in respect of the extent of the
      rise in melting point and in respect of its dependence upon polymer length. An
      additional dependence upon the identify of the polymer was attributed to detailed
      effects of shape in solution.

PMID- 17007784
TI  - Properties of strange attractors in yeast glycolysis.
AB  - The properties of periodic and aperiodic glycolytic oscillations observed in
      yeast extracts under sinusoidal glucose input were analyzed by the following
      methods. (1) Spectral analysis, rendering sharp peaks for periodic responses and
      enhanced broad-band noise for aperiodic oscillations. (2) Phase plane analysis,
      leading to closed and to open trajectories for periodic and aperiodic
      oscillations, respectively. (3) Rotation of a phase plane proportionally to time,
      revealing strange attractors associated with the aperiodic oscillations. (4)
      Stroboscopic plot on the phase plane, showing that the strange attractors follow
      a stretch-fold-press process, if the stroboscoping phase is varied. (5)
      Stroboscopic transfer plot, admitting a period of three transfer processes and
      thus implying chaos according to the Li-Yorke theorem. (6) Determination of the
      rate of information production by differentiation of the transfer plot, yielding
      approx. 0.21 bits per min for the chaotically glycolyzing yeast extract.

PMID- 17007785
TI  - On the oscillatory phenomenon in an oil/water interface.
AB  - A simple theoretical model is presented for simulating the self-sustained
      oscillations of electric potential and pH at an oil/water interface appearing in
      a two-phase system composed of 2-nitropropane solution containing picrate acid
      and an aqueous solution of cetyltrimethylammonium bromide. In the present model,
      a well-known condition necessary for the occurrence of self-sustained
      oscillations, i.e., the presence of a positive feedback process far from
      equilibrium, is taken into account in a set of kinetic equations to describe
      simplified characters of the following two processes: (i) a cooperative formation
      of ion pair complexes at the interface, and (ii) supply of picrate anions and
      cetyltrimethylammonium cations to the interface accompanied by release of ion
      pair complexes to the organic phase. The numerical solutions of the present
      equations are shown to reproduce fairly well the characteristic properties of the
      oscillation of electric potential and pH such as wave forms and frequencies.

PMID- 17007786
TI  - Thermodynamics of the conversion of aqueous xylose to xylulose.
AB  - The thermodynamics of the conversion of aqueous xylose to xylulose has been
      investigated using high-pressure liquid chromatography (HPLC) and
      microcalorimetry. The reaction was carried out in aqueous phosphate buffer over
      the pH range 6.8-7.4 using solubilized glucose isomerase with MgSO(4) as a
      cofactor. The temperature range over which this reaction was investigated was
      298.15-342.15 K. A combined analysis of both the HPLC and microcalorimetric data
      leads to the following results at 298.15 K for the conversion process: DeltaG
      degrees = 4389 +/- 31 J mol(-1), DeltaH degrees = 16090 +/- 670 J mol(-1), and
      DeltaC(p) degrees = 40 +/- 23 J mol(-1) K(-1). The temperature dependence of the
      equilibrium constant for the reaction is expressed as R ln K = -4389/298.15
      +16090[(1/298.15)-(1/T)]+40[(298.15/T)-1 + ln(T/298.15)]. Comparisons are made
      with literature data.

PMID- 17007787
TI  - Heterogeneous binding of oxygen and carbon monoxide to dissociated molluscan
      hemocyanin.
AB  - Functional heterogeneity in O2 or CO binding of sites of dissociated molluscan
      hemocyanin polypeptide chains (Helix pomatia and Octopus vulgaris) has been
      estimated by an analysis of accurate noncooperative binding curves. Three types
      of experiments were performed: pure O2 or CO binding, competitive displacement of
      one ligand by the other, and simultaneous removal of both gases from protein
      partially saturated with O2 and CO. The data were analyzed in terms of a model
      which has two fractions of sites with different properties for O2 and CO. The
      relative proportion of the different binding sites and their affinity constant
      values were found by the combined use of the three different procedures. All
      species show a marked functional heterogeneity of sites for O2 binding, while for
      CO binding it has been observed only in the case of H. pomatia beta-hemocyanin.
      Moreover, in all three molluscan hemocyanins examined, the two classes of O2
      binding sites, although present in different proportions within the polypeptide
      chains, display similar affinity constant values. The data reported show a good
      consistency with results obtained using digested and isolated domains, providing
      confidence in the analytical procedure used. From comparison of the O2/CO
      affinity ratios (KO2, KCO) of each class it may be suggested that the difference
      in O2 affinity of two kinds of binding sites is related to a different local
      structure of the active sites. The results, moreover, unequivocally confirm that
      binding and displacement of two gaseous ligands to hemocyanin occur by a simple
      competitive mechanism, although the binding site is structurally complex and the
      two ligands are bound with different geometries.

PMID- 17007788
TI  - Dynamic light scattering from dilute suspensions of thin discs and thin rods as
      limiting forms of cylinder, ellipsoid and ellipsoidal shell of revolution.
AB  - A previous formulation of the field correlation function G1(tau) of light
      quasielastically scattered from suspensions of rigid rods undergoing anisotropic
      translational as well as rotational diffusion (T. Maeda and S. Fujime,
      Macromolecules 17 (1984) 1157) was extended to the cases of suspensions of
      cylinders (length L and radius R), ellipsoids and ellipsoidal shells of
      revolution (x2/b2 + y2/b2 + z2/a2 = 1). The present formulation includes that for
      suspensions of rigid rods in the limit of KR 1 or in the limit of b/a 1 and Kb 1
      (an extremely prolate ellipsoid), and also that for suspensions of discs in the
      limit of KL 1 or in the limit of b/a 1 and Ka 1 (an extremely oblate ellipsoid),
      where K is the length of the scattering vector. Explicit forms of G1(tau), of the
      first cumulant Gamma of G1(tau) and of the dynamic form factors will be given,
      and numerical methods suitable for computation of dynamic form factors will be
      discussed. The present results can be applied to the analysis of experimental
      data for dilute suspensions of thin rods and thin discs. When the situation is
      favorable, our method can provide transport coefficients D1, D3, and Theta from
      dynamic light-scattering data only, where D(1) and D(3) are, respectively, the
      translational diffusion coefficients parallel with the x (y) and z axes, and
      Theta the rotational diffusion coefficient around the x (y) axis.

PMID- 17007789
TI  - Dynamic light scattering study of suspensions of purple membrane.
AB  - Purple membrane from Halobacterium halobium in suspensions has been studied by
      quasielastic light scattering. The intensity correlation functions of polarized
      scattered light were measured at various K2 values (K being the magnitude of the
      scattering vector), and the first cumulant Gamma of the field correlation
      function G1(tau) was obtained by a cumulant expansion method. The apparent
      diffusion coefficient Gamma /K2 did not increase monotonically with K2 values and
      showed a distinct anomaly in an intermediate range of K. A theoretical
      formulation of G1(tau) for a disc and an extremely oblate ellipsoidal shell of
      revolution (S. Fujime and K. Kubota, Biophys. Chem. 23 (1985) 1) was applied to
      the analysis of the spectra, and characteristic features of experimental spectra
      were well reproduced. It was suggested that a strong interference effect between
      scattered rays on Gamma /K2 should be attributed to a slight noncircular shape of
      the purple membrane and that a contribution to Gamma /K2 from membrane
      flexibility should be taken into account. This study will provide experimental
      evidence of the feasibility of membrane studies by dynamic light scattering.

PMID- 17007790
TI  - Studies on the interaction between alkali metal cations and polyion by sound
      velocity.
AB  - The sound velocities in polyelectrolyte solutions were measured at various
      concentrations of added salts. When aqueous solutions of tetra (n-butyl)ammonium
      polyacrylate were titrated with concentrated solutions of LiCl, NaCl, KCl or
      CsCl, the sound velocity, i.e., the adiabatic compressibility of the solution,
      did not change linearly with added salt concentration, but showed a breaking
      point. The degrees of counterion binding on polyacrylate ion estimated from the
      breaking points were 0.25-0.30, independent of cation species. In
      polystyrenesulfonate, moreover, no Na+ binding was detected from such sound
      velocity measurements.

PMID- 17007791
TI  - Magnesium-sugar interaction. Synthesis, spectroscopic and structural
      characterization of Mg-sugar complexes containing beta-D-fructose.
AB  - The interaction between beta-D-fructose and hydrated magnesium salts has been
      studied and complexes of the type Mg(beta-D-fructose)Cl2.4H2O and Mg(beta-D
      fructose)Br2.4H2O have been isolated and characterized. On the basis of
      comparisons of the spectroscopic and other chemical properties of several
      structurally known calcium-fructose compounds with those of the corresponding
      magnesium complexes, it is concluded that Mg2+ binds to two sugar moieties via
      O(2), O(3) of the first and O(4), O(5) of the second and to two water molecules,
      resulting in a six-coordinate geometry around the Mg2+. The strong sugar hydrogen
      bonding network is rearranged upon sugar metallation and the sugar moiety shows
      the beta-anomer conformation in these magnesium-sugar complexes.

PMID- 17007792
TI  - Dynamic properties of bacteriorhodopsin in purple membranes upon heat treatment.
AB  - Reversible temperature-dependent conformational changes in bacteriorhodopsin of
      the purple membranes from Halobacterium halobium have been studied by the method
      of deuterium exchange. A noticeable increase in the mobility of structured
      peptide groups in bacteriorhodopsin was revealed upon reorganization of the
      supermolecular structure at about 60 degrees C. In the supermolecular structure
      formed, bacteriorhodopsin molecules have no contacts with external medium at 75
      80 degrees C. Membrane destruction results in a drastic increase in molecular
      mobility within the narrow temperature range 100-110 degrees C. The effects
      observed are induced by predenaturation changes in the bacteriorhodopsin
      structure and rearrangements in the structure of a protein-lipid complex. The
      temperature dependence of the number of peptide groups involved in reversible
      conformational rearrangements is in good agreement with the microcalorimetry
      data.

PMID- 17007793
TI  - Kinetic study of transfer of 11-cis-retinal between rod outer segment membranes
      using regeneration of rhodopsin.
AB  - The present study demonstrates some important facts on the regeneration of
      rhodopsin in rod outer segment membranes. 11-cis-Retinal added to a rod outer
      segment membrane suspension did not react directly with opsin but was rapidly
      solubilized into membranes and then recombined with opsin in the membrane. It was
      also revealed that the regeneration of rhodopsin was perturbed by the formation
      of retinylidene Schiff base with phosphatidylethanolamine in rod outer segment
      membranes, which decreased with increasing temperature. The activation energy of
      rhodopsin regeneration in rod outer segment membranes was 18.7 kcal/mol, being
      smaller than the value of 22 kcal/mol in 1% digitonin solution. 11-cis-Retinal
      could be found to transfer relatively fast (tau-1/k(1) R 10(3) s) between rod
      outer segment membranes by using the regeneration of rhodopsin. It was
      demonstrated that the kinetic measurement for the transport of membrane-soluble
      molecules such as retinal between membranes could be perform ed with ease and
      precisely by the method described in this paper.

PMID- 17007794
TI  - Thermodynamics of the conversion of aqueous L-aspartic acid to fumaric acid and
      ammonia.
AB  - The thermodynamics of the conversion of aqueous L-aspartic acid to fumaric acid
      and ammonia have been investigated using both heat conduction microcalorimetry
      and high-pressure liquid chromatography. The reaction was carried out in aqueous
      phosphate buffer over the pH range 7.25-7.43, the temperature range 13-43 degrees
      C, and at ionic strengths varying from 0.066 to 0.366 mol kg(-1). The following
      values have been found for the conversion of aqueous L-aspartateH- to fumarate2-
      and NH4+ at 25 degrees C and at zero ionic strength: K = (1.48 +/- 0.10) x 10(
      3), DeltaG degrees = 16.15 +/- 0.16 kJ mol(-1), DeltaH degrees = 24.5 +/- 1.0 kJ
      mol(-1), and DeltaC(p) degrees = -147 +/- 100 J mol(-1) K(-1). Calculations have
      also been performed which give values of the apparent equilibrium constant for
      the conversion of L-aspartic acid to fumaric acid and ammonia as a function of
      temperature, pH and ionic strength.

PMID- 17007795
TI  - Subzero-temperature preservation of reactive fluids in the undercooled state. I.
      The reduction of potassium ferricyanide by potassium cyanide.
AB  - Many reactions show enhanced rates at subzero temperatures due to freeze
      concentration. The reduction of potassium ferricyanide by potassium cyanide has
      been studied at subzero temperatures in both the undercooled and the frozen
      state. The pseudo-first-order rate constants calculated differ greatly from those
      in previous reports. A high degree of freeze concentration and supersaturation in
      frozen bulk solutions occurs. It has been clearly demonstrated that undercooled
      preservation provides a useful method for the long-term storage of reactive
      mixtures.

PMID- 17007796
TI  - 1H, 7Li and 133Cs multicomponent self-diffusion NMR study on ion binding of Li+
      and Cs+ to nucleotides and aggregation of nucleotides in aqueous solution.
AB  - The Fourier transform NMR pulsed-gradient spin-echo self-diffusion technique was
      used for studies of nucleotides (AMP, CMP, GMP and UMP) with Li+ or Cs+ added, in
      2H2O. 1H-, 7Li- and 133Cs-NMR-based self-diffusion data on the constituents
      provide a picture of both the degree of ion binding to nucleotides and the self
      association of nucleotides in aqueous solution. Self-diffusion coefficients were
      investigated in a concentration range up to 0.3 molal nucleotide in 2H2O, while
      keeping the metal ion concentration of Li+ or Cs+ at twice the nucleotide
      concentration throughout the investigations. The self-association studies reveal
      that the aggregation constants of the Li salts differ only slightly from the
      corresponding constants for the disodium salts of the mononucleotides. Within a
      two-site bound-free model for the counterions and a cooperative indefinite
      aggregation model for the nucleotides one finds that the degree of ion binding
      for all these nucleotide systems remains approximately constant, in spite of
      increasing aggregate concentration. This corresponds to the well-known
      polyelectrolyte ion condensation behaviour, indicating that large aggregates are
      formed, supporting previous findings by the present authors on the aggregation
      behaviour of nucleotides. An observed large effect on the 17O relaxation of water
      in nucleotide systems can only be reconciled with the presence of relatively
      large aggregates in solution.

PMID- 17007797
TI  - Indo-mo investigation of gas-phase acidities of carbamates and thiocarbamates.
AB  - Gas-phase anion proton affinities of carbamic (I), thiol- (II), thio- (III) and
      dithiocarbamic (IV) acids are calculated by the INDO-MO method employing energy
      gradients for full geometry optimizations. The effect of d-type functions on
      sulphur on the calculated proton affinities has been examined. Detailed energy
      partitioning analysis enabled a much better understanding of the protonation
      process. Energetics of the isomerization II --> III have been computed and
      discussed.

PMID- 17007798
TI  - Analysis of multi-component fluorescence emission by phase-sensitive detection
      using one modulation frequency.
AB  - We describe the use of phase-sensitive detection of fluorescence to resolve the
      lifetimes and fractional intensities from multi-component fluorescence samples,
      using data obtained at a single modulation frequency. Phase-sensitive spectra of
      the mixture are recorded at arbitrarily chosen detector phase angles. The steady
      state spectrum of each component must be known. The phase-sensitive spectra are
      fitted, using a nonlinear least-squares algorithm, to obtain the lifetimes and
      fractional intensities of each fluorophore in the mixture. Simulations for two-
      and three-component mixtures are presented to illustrate how the resolution is
      affected by spectral overlap and lifetime separation. Experimentally, we resolved
      two- and three-component mixtures of protein-like fluorophores (N-acetyl-L
      tyrosinamide, N-acetyl- L-tryptophanamide, indole and 2,3-dimethylindole) using
      data collected at 30 MHz. These fluorophores have closely spaced lifetimes of
      1.5, 2.9, 4.5 and 4.3 ns, respectively, and display extensive spectral overlap.
      These results demonstrate that phase-sensitive spectra, recorded at only one
      modulation frequency with a standard phase fluorometer, can be used to resolve
      multi-component emissions.

PMID- 17007799
TI  - Photoacoustic spectroscopy of purple membrane fragments. Evidence for disorder
      during photocycle.
AB  - A strong band at 412 nm has been observed in the photoacoustic spectrum of
      partially dried purple membrane, peaking sharply at a modulation frequency of
      about 70 Hz. This may be explained in terms of a disorder-order transition.

PMID- 17007800
TI  - Interactions of myoglobin with urea and some alkylureas. II. Calorimetric and
      circular dichroic studies.
AB  - The interactions of myoglobin with urea, methyl-, N,N'-dimethyl- and ethylurea
      were studied by means of calorimetry and circular dichroism (CD). The enthalpies
      of transfer from water to aqueous denaturant solutions are positive for the
      alkylureas and negative for urea. The difference is due to the presence of
      hydrophobic groups in the alkylureas. Gibbs free energies of transfer for urea
      solutions were obtained from preferential binding data determined previously. An
      attempt is made to interpret the values of the thermodynamic quantities in terms
      of various interactions between protein and denaturant. Analysis of the far
      ultraviolet CD spectra reveals some differences in the denaturing activity of
      urea and the alkylureas, the latter being stronger denaturants than urea.
      Myoglobin displays relatively high stability towards these denaturants since
      concentrations above 5 M are needed for achieving major conformational changes.

PMID- 17007801
TI  - Subzero-temperature preservation of reactive fluids in the undercooled state. II.
      The effect on the oxidation of ascorbic acid of freeze concentration and
      undercooling.
AB  - The rate of oxidation of ascorbic acid has been measured in both frozen and
      undercooled solutions. A new interpretation is advanced for changes in the rate
      of ascorbic acid oxidation in freeze-concentrated solutions. The results obtained
      with undercooled solutions indicate a rate reduction in line with that predicted
      by the Arrhenius equation. It is also demonstrated that undercoohng provides a
      method for greatly extending the shelf life of reactive fluids.

PMID- 17007802
TI  - Thermodynamics of carbohydrate isomerization reactions. The conversion of aqueous
      allose to psicose.
AB  - The thermodynamics of the conversion of aqueous D-psicose to D-allose has been
      investigated using high-pressure liquid chromatography. The reaction was carried
      out in phosphate buffer at pH 7.4 over the temperature range 317.25-349.25 K. The
      following results are obtained for the conversion process at 298.15 K: DeltaG
      degrees = - 1.41 +/- 0.09 kJ mol(-1), DeltaH degrees = 7.42 +/- 1.7 kJ mol(-1),
      and DeltaC(p) degrees = 67 +/- 50 J mol(-1) K(-1). An approximate equilibrium
      constant of 0.30 is obtained at 333.15 K for the conversion of aqueous D-psicose
      to D-altrose. Available thermodynamic data for isomerization reactions involving
      aldohexoses and aldopentoses are summarized.

PMID- 17007803
TI  - Discrimination of tertiary and quaternary Bohr effect in the O2 binding of Helix
      pomatia beta-hemocyanin.
AB  - Simultaneous determination of proton uptake and oxygen binding has been carried
      out on Helix pomatia beta-hemocyanin under equilibrium conditions in the absence
      of buffer and at different initial pH values. Oxygen-binding isotherms of
      unbuffered H. pomatia beta-hemocyanin, in the presence of phenol red as pH
      indicator, have been determined employing a thin-layer apparatus. Application of
      this very accurate technique allows monitoring of proton uptake (or release)
      coupled to O2-binding also at extremes of saturation which are often difficult to
      explore and analyze. The data have been analyzed within the framework of the
      cooperon model (M. Brunori, M. Coletta and E. Di Cera, Biophys. Chem. 23 (1986)
      215) and compared with those obtained in the presence of buffer. Comparison of pH
      changes with ligand binding of the T state over all the saturation range has
      allowed us to discriminate and obtain quantitative estimates of the Bohr protons
      associated with both oxygenation of the T state and quaternary allosteric
      transition; no protons are taken up or released during oxygenation of the R
      state. These results differ quantitatively from those obtained in the presence of
      buffer, which alters significantly the T state contribution to the overall Bohr
      effect.

PMID- 17007804
TI  - Eye movement correlates of younger and older adults' strategies for complex
      addition.
AB  - This study examined performance measures and eye movements associated with
      complex arithmetic strategies in young and older adults. Participants added pairs
      of three-digit numbers using two different strategies, under choice and no-choice
      conditions. Older adults made more errors but were not significantly slower than
      young adults, and response times and errors showed no interaction between age and
      the number of carries. Older adults chose strategies less adaptively than young
      adults. Eye movements were consistent with use of required strategies on no
      choice trials and reported strategies on choice trials. Eye movement data also
      suggested that young adults more successfully distinguished between strategies.
      Implications of these findings for understanding aging effects in complex
      arithmetic are discussed.

PMID- 17007805
TI  - The host's genetic background determines the extent of angiogenesis induced by
      schistosome egg antigens.
AB  - Schistosomiasis is characterised by periovular granuloma formation within the
      portal tract and presinusoidal venules. As inflammation wanes, continued attempts
      to wall off and repair hepatic injury, lead to the development of extensive
      fibrosis. The codependence of chronic inflammation and angiogenesis is a well
      known phenomenon. Neovascularisation is a complex process of endothelial cell
      proliferation and remodelling of the extracellular matrix. Previous studies
      demonstrated the ability of schistosome soluble egg antigens (SEAs) to stimulate
      endothelial cell activation in vitro. In the present study, we investigated the
      angiogenic potential of SEA in Swiss and BALb/c mice, after infection with
      Schistosoma mansoni or S. haematobium and by implanting SEA-coated beads into the
      murine liver. Anti-CD34 and anti-Ki-67 immunohistochemical stainings demonstrated
      newly formed blood vessels within and at the periphery of the granulomas.
      However, in one third of the granulomas the pre-existing portal stroma was not
      destroyed by the granulomatous inflammation, angiogenesis was minimal or absent
      and further growth of the granuloma was prevented. In C57BL/6J and C3H/HeN inbred
      mice, this polarisation was even more pronounced. In 91% of the granulomas in
      C57BL6/J mice the portal stroma was preserved. These mice had significantly
      smaller granulomas, less fibrosis and less mortality as compared to the high
      pathology C3H/HeN mice, where 87% of the granulomas were of the angiogenic type
      with destruction of the pre-existing stroma, leading to more severe chronic
      pathology. Thus, host's genetic mechanisms regulating the degree of angiogenesis
      and fibrosis, determine the severity of schistosome-induced pathology.

PMID- 17007807
TI  - Detection of reversible protein thiol modifications in tissues.
AB  - Oxidation/reduction reactions of protein thiol groups (PSH) have been implicated
      in many physiological and pathological processes. Although many new techniques
      for separation and identification of modified cysteinyl residues in proteins have
      been developed, critical assessment of reagents and sample processing often are
      overlooked. We carefully compared the effectiveness of N-ethylmaleimide (NEM),
      iodoacetamide (IAM), and iodoacetic acid (IAA) in alkylating protein thiols and
      found that NEM required less reagent (125 vs. 1000 mol:mol excess), required less
      time (4 min vs. 4h), and was more effective at lower pHs (4.3 vs. 8.0) in
      comparison with IAM and IAA. The relative efficacy of dithiothreitol (DTT) and
      tris(2-carboxyethyl)phosphine (TCEP) for reducing protein disulfides suspended in
      NaPO(4) buffer or MeOH was assessed, and no differences in total normalized
      fluorescence were detected at the concentrations tested (10-100mM); however,
      individual band resolution appeared better in samples reduced with DTT in MeOH.
      In addition, we found that oxidation ex vivo was minimized in tissue samples that
      were homogenized in aqueous buffers containing excess molar quantities of NEM
      compared with samples homogenized in MeOH containing NEM. Using NEM for thiol
      alkylation, DTT for disulfide reduction, and mBBr for labeling the reduced
      disulfide and fluorimetric detection, we were able to generate an in-gel standard
      curve and quantitate total disulfide contents within biological samples as well
      as to identify changes in specific protein bands by scanning densitometry. We
      demonstrated that reagents and techniques we have identified for disulfide
      detection in complex samples are also applicable to two-dimensional
      electrophoresis separations.

PMID- 17007806
TI  - Comparative analysis of 10 small molecules binding to carbonic anhydrase II by
      different investigators using Biacore technology.
AB  - In this benchmark study, 26 investigators were asked to characterize the kinetics
      and affinities of 10 sulfonamide inhibitors binding to the enzyme carbonic
      anhydrase II using Biacore optical biosensors. A majority of the participants
      collected data that could be fit to a 1:1 interaction model, but a subset of the
      data sets obtained from some instruments were of poor quality. The experimental
      errors in the k(a), k(d), and K(D) parameters determined for each of the
      compounds averaged 34, 24, and 37%, respectively. As expected, the greatest
      variation in the reported constants was observed for compounds with exceptionally
      weak affinity and/or fast association rates. The binding constants determined
      using the biosensor correlated well with solution-based titration calorimetry
      measurements. The results of this study provide insight into the challenges, as
      well as the level of experimental variation, that one would expect to observe
      when using Biacore technology for small molecule analyses.

PMID- 17007808
TI  - Absolute quantitation of microRNAs with a PCR-based assay.

PMID- 17007809
TI  - Anxiety-related biases in children's avoidant responses to a masked angry face.
AB  - While anxious children often show escape and withdrawal behaviours towards
      threats, few studies have experimentally assessed avoidance. The present study
      examined whether children with high levels of anxiety showed more avoidant
      responses to a neutral conditioned cue (CS+) that was paired with an
      unconditioned threat stimulus (UCS), a masked angry facial expression. Thirty-six
      10 and 11 year-olds participated in a task, which involved choosing between two
      CS card stimuli of different colours to win points. Whilst both cards awarded the
      same number of points, one colour was systematically paired with a masked angry
      face (CS+), whilst the other colour was paired with a masked neutral face (CS-).
      Children with higher anxiety scores had an overall tendency to choose the card
      associated with the neutral face, with some evidence suggesting that this
      tendency emerged gradually across trials. These results suggest a relationship
      between anxiety and stimulus-response learning for CS+-UCS associations that
      support behavioural avoidance.

PMID- 17007810
TI  - Responsibility to continue thinking and worrying: evidence of incremental
      validity.
AB  - This two-part study examined the role of the responsibility to continue thinking,
      beliefs that one needs prolonged thinking about stressful problems, in the
      prediction of excessive worry. This construct is considered to reflect high
      levels of motivation to continue inflexible thinking and the use of rigid stop
      rules. In Study 1, 122 students completed questionnaires. A regression analysis
      revealed that responsibility accounted for a unique variance beyond negative meta
      cognitive beliefs about worry. One hundred and fifty students participated in
      Study 2, where worry was regressed on emotional instability (Neuroticism),
      responsibility, and other worry-related cognitive variables (intolerance of
      uncertainty, positive/negative meta-cognitive beliefs, poor problem-solving
      orientation, and cognitive avoidance). Again, responsibility was a significant
      predictor, after controlling for emotional instability (Neuroticism) and other
      worry-related cognitions. These results indicate the incremental validity of the
      responsibility to continue thinking.

PMID- 17007811
TI  - Neuropsychological functioning in kleptomania.
AB  - Kleptomania is characterized by the failure to resist impulses to steal objects
      not needed for personal use or their monetary value. The objective of this study
      was to examine cognitive and executive functioning in subjects with kleptomania.
      Fifteen women with a primary DSM-IV diagnosis of kleptomania underwent a detailed
      psychiatric examination, including measures of kleptomania severity, and a
      battery of neuropsychological tests that emphasized executive functions.
      Correlational analyses were computed between measures of kleptomania severity and
      tests of executive functioning. Kleptomania subjects reported a mean duration of
      illness of 17.9 years and shoplifting a mean of 1.7 times per week. All subjects
      reported an inability to resist urges to shoplift. Neuropsychological testing
      revealed group mean test scores within 0.5 standard deviations of normative
      standards for age. Five subjects (33.3%), however, had below-average performance
      on at least one measure of executive functioning, and 4 (26.7%) had below-average
      scores on two executive measures. Correlational analyses revealed a statistically
      significant correlation between kleptomania severity and Wisconsin Card Sorting
      Test performance (r=-0.693, p=0.004). As a group, subjects with kleptomania did
      not demonstrate deficits on neuropsychological testing. Greater kleptomania
      symptom severity, however, was correlated with impairment in executive
      functioning.

PMID- 17007812
TI  - Randomized trial of a brief depression prevention program: an elusive search for
      a psychosocial placebo control condition.
AB  - This trial compared a brief group cognitive-behavioral (CBT) depression
      prevention program to a waitlist control condition and four placebo or
      alternative interventions. High-risk adolescents with elevated depressive
      symptoms (N=225, M age=18, 70% female) were randomized to CBT, supportive
      expressive group intervention, bibliotherapy, expressive writing, journaling, or
      waitlist conditions and completed assessments at baseline, termination, and 1-
      and 6-month follow-up. All five active interventions showed significantly greater
      reductions in depressive symptoms at termination than waitlist controls; effects
      for CBT and bibliotherapy persisted into follow-up. CBT, supportive-expressive,
      and bibliotherapy participants also showed significantly greater decreases in
      depressive symptoms than expressive writing and journaling participants at
      certain follow-up points. Findings suggest there may be multiple ways to reduce
      depressive symptoms in high-risk adolescents, although expectancies, demand
      characteristics, and attention may have contributed to the observed effects.

PMID- 17007813
TI  - Social anxiety disorder in childhood and adolescence: descriptive
      psychopathology.
AB  - Although the presentation of social anxiety disorder (SAD) in adults is well
      documented, less is known about its clinical manifestation in children and
      adolescents. To date, most studies have included combined samples of children and
      adolescents despite the fact that this age range represents an extensive period
      of growth and development. This study compares and contrasts the clinical
      presentation of SAD among children (ages 7-12) and adolescents (ages 13-17). One
      hundred and fifty children (n=74) and adolescents (n=76) with a primary diagnosis
      of SAD participated in the study. The assessment battery included clinical
      ratings and behavioral observation as well as parental and self-report. The
      results indicate that, although the symptom presentation of children and
      adolescents with primary SAD shares many features, children tend to present with
      a broader pattern of general psychopathology, while adolescents have a more
      pervasive pattern of social dysfunction and may be more functionally impaired as
      a result of their disorder. These findings suggest that interventions for SAD
      need to carefully consider clinical presentation of the disorder as it manifests
      in childhood and adolescence.

PMID- 17007814
TI  - The crystal structure of L-lactate oxidase from Aerococcus viridans at 2.1A
      resolution reveals the mechanism of strict substrate recognition.
AB  - L-Lactate oxidase (LOX) from Aerococcus viridans is a member of the alpha
      hydroxyacid-oxidase flavoenzyme family. We have determined the three-dimensional
      structure of LOX and revealed the mechanism of substrate recognition. The LOX
      monomer structure has a typical alpha(8)/beta(8) motif commonly found in other
      flavin family proteins. A related enzyme, glycolate oxidase, catalyzes the
      oxidation of glycolate rather than lactate. Comparison of the two enzyme
      structures highlights the importance of five residues around the FMN prosthetic
      group of LOX, which act synergistically to discriminate between the l/d
      configurations of lactate. X-ray crystallography of LOX gave a space group I422
      of unit-cell parameters a=b=191.096A, c=194.497A and alpha=beta=gamma=90 degrees
      with four monomers per asymmetric unit. The four independent monomers display
      slight structural differences around the active site. Diffraction data were
      collected, under cryogenic conditions to 2.1A resolution at the synchrotron
      facilities in Japan.

PMID- 17007815
TI  - Activation of mitochondrial promoter P(H)-binding protein in a radio-resistant
      Chinese hamster cell strain associated with Bcl-2.
AB  - The cellular response to ionizing radiation is mediated by a complex interaction
      of number of proteins involving different pathways. Previously, we have shown
      that up regulation of mitochondrial genes ND1, ND4, and COX1 transcribed from the
      heavy strand promoter (P(H)) has been increased in a radio-resistant cell strain
      designated as M5 in comparison with the parental Chinese hamster V79 cells. These
      genes are also up regulated in Chinese hamster V79 cells VB13 that express
      exogenous human Bcl2. In the present study, the expression of the gene ND6 that
      is expressed from the light strand promoter (P(L)) was found to be similar in
      both the cell lines, as determined by RT-PCR. To test the possibility that this
      differential expression of mitochondrial genes under these two promoters was
      mediated by differences in proteins' affinity to interact with these promoters,
      we have carried out electrophoretic mobility shift assay (EMSA) using
      mitochondrial cell extracts from these two cell lines. Our result of these
      experiments revealed that two different proteins formed complex with the
      synthetic promoters and higher amount of protein from M5 cell extracts interacted
      with the P(H) promoter in comparison to that observed with cell extracts from
      Chinese hamster V79 cells. The promoter-specific differential binding of proteins
      was also observed in VB13. These results showed that differential mitochondrial
      gene expression observed earlier in the radio-resistant M5 cells was due to
      enhanced interaction proteins with the promoters P(H) and mediated by the
      expression of Bcl2.

PMID- 17007816
TI  - MT1-MMP shedding involves an ADAM and is independent of its localization in lipid
      rafts.
AB  - The membrane type 1-matrix metalloproteinase (MT1-MMP) is a membrane-anchored
      protease that its entire ectodomain is shed from the cell surface. Here we show
      that in HT1080 cells MT1-MMP is shed as two soluble forms of approximately 52 and
      approximately 50kDa. Analyses in purified HT1080 plasma membranes show that
      release of these species is a two-step time-dependent process that is mediated by
      integral membrane metalloprotease(s). Differential sensitivity to TIMP-3
      inhibition of the shedding process suggests that the second cleavage step leading
      to the formation of the 50-kDa soluble species is mediated by an ADAM. We also
      show that shedding of MT1-MMP is independent of its partition into lipid rafts
      because both wild type and glycosylphosphatidylinositol (GPI)-anchored MT1-MMP
      are shed. These studies provide new insights into the process of MT1-MMP
      ectodomain shedding, which may regulate pericellular proteolysis.

PMID- 17007817
TI  - Polycystin-1 promotes PKCalpha-mediated NF-kappaB activation in kidney cells.
AB  - Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates
      many cell functions, including cell proliferation and apoptosis, both typically
      increased in cyst lining cells in autosomal dominant polycystic kidney disease.
      Here we show that PC1 upregulates the NF-kappaB signalling pathway in kidney
      cells to prevent cell death. Human embryonic kidney cell lines (HEK293(CTT)),
      stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF
      kappaB nuclear levels and NF-kappaB-mediated luciferase promoter activity. This,
      consistently, was reduced in HEK293 cells in which the endogenous PC1 was
      depleted by RNA interference. CTT-dependent NF-kappaB promoter activation was
      mediated by PKCalpha because it was blocked by its specific inhibitor Ro-320432.
      Furthermore, it was observed that apoptosis, which was increased in PC1-depleted
      cells, was reduced in HEK293(CTT) cells and in porcine kidney LtTA cells
      expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and
      parthenolide, a NF-kappaB inhibitor, significantly reduced the CTT-dependent
      antiapoptotic effect. These data reveal, therefore, a novel pathway by which
      polycystin-1 activates a PKCalpha-mediated NF-kappaB signalling and cell
      survival.

PMID- 17007818
TI  - Pharmacological inhibition of poly(ADP-ribose) polymerase inhibits angiogenesis.
AB  - Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which plays an important
      role in regulating cell death and cellular responses to DNA repair.
      Pharmacological inhibitors of PARP are being considered as treatment for cancer
      both in monotherapy as well as in combination with chemotherapeutic agents and
      radiation, and were also reported to be protective against untoward effects
      exerted by certain anticancer drugs. Here we show that pharmacological inhibition
      of PARP with 3-aminobenzamide or PJ-34 dose-dependently reduces VEGF-induced
      proliferation, migration, and tube formation of human umbilical vein endothelial
      cells in vitro. These results suggest that treatment with PARP inhibitors may
      exert additional benefits in various cancers and retinopathies by decreasing
      angiogenesis.

PMID- 17007819
TI  - Differential hypothalamic neuronal activation following peripheral injection of
      GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance
      imaging.
AB  - The anorexigenic gut hormones oxyntomodulin (OXM) and glucagon-like peptide-1
      (GLP-1) are thought to physiologically regulate appetite and food intake. Using
      manganese-enhanced magnetic resonance imaging, we have shown distinct patterns of
      neuronal activation in the hypothalamus in response to intraperitoneal injections
      into fasted mice of 900 and 5400 nmol/kg OXM or 900 nmol/kg GLP-1. Administration
      of OXM at either dose resulted in a reduced rate of signal enhancement,
      reflecting a reduction in neuronal activity, in the arcuate, paraventricular, and
      supraoptic nuclei of the hypothalamus. Conversely, GLP-1 caused a reduction in
      signal enhancement in the paraventricular nucleus only and an increase in the
      ventromedial hypothalamic nucleus. Our data show that these two apparently
      similar peptides generate distinct patterns of activation within the
      hypothalamus, suggesting that GLP-1 and OXM may act via different hypothalamic
      pathways.

PMID- 17007820
TI  - The immunoglobulin-like domain is involved in interaction of Neuregulin1 with
      ErbB.
AB  - Neuregulin1 (NRG1) is a growth factor that signals through the interaction of the
      epidermal growth factor (EGF)-like domain with ErbB receptors. An immunoglobulin
      (Ig)-like domain is contained together with EGF-like domain in the ectodomain of
      some isoforms generated by alternative splicing, but its role in NRG1 signaling
      remained unclear. In the present study, we identified a novel isoform of NRG1
      containing an Ig-like domain conserved among species from adult Xenopus laevis,
      which is predominantly expressed in the testis and brain. We generated
      recombinant proteins for the whole ectodomain and EGF-like domain alone of the
      isoform to compare their effects on cell proliferation, and phosphorylation of
      and their association with ErbB receptor, demonstrating that the ectodomain had
      approximately 10(3)-fold higher abilities than the EGF-like domain. Therefore,
      the Ig-like domain is probably essential for efficient interaction of an EGF-like
      domain with ErbB receptors.

PMID- 17007821
TI  - R-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo-[1,2,3-de]-1,4
      benzoxazin-6-yl]-1-naphtalenylmethanone (WIN-2) ameliorates experimental
      autoimmune encephalomyelitis and induces encephalitogenic T cell apoptosis:
      partial involvement of the CB(2) receptor.
AB  - Many reports have shown that cannabinoids might be beneficial in the symptomatic
      treatment of multiple sclerosis (MS). We have investigated the therapeutic
      properties of the non-selective cannabinoid receptor agonist WIN-2 as a
      suppressive drug in the experimental autoimmune encephalomyelitis (EAE) model of
      MS. In the passive variety of EAE, induced in Lewis rats by adoptive transfer of
      myelin-reactive T cells, WIN-2 ameliorates the clinical signs and diminishes the
      cell infiltration of the spinal cord. Due to the involvement of cannabinoids in
      the regulation of cell death and survival, we investigated the effects of WIN-2
      on the encephalitogenic T cell population. WIN-2 induced a profound increase of
      apoptosis in a dose- and time-dependent manner. The potential involvement of
      cannabinoid receptors (CB) was investigated by encephalitogenic T cell
      stimulation in the presence of the CB(1) (SR141716A) and CB(2) (SR144528)
      antagonists, pertussis toxin (PTX) and the inactive enantiomer WIN-3. WIN-2
      induced apoptosis was partially blocked by SR144528 and PTX, whereas, WIN-3 only
      exerted a mild effect on cell viability. These results point to the partial
      involvement of CB(2) receptor together with other receptor-independent mechanism
      or by yet unknown cannabinoid receptors. Moreover, WIN-2 induced the extrinsic
      pathway of apoptosis, as shown by caspase-10 and -3 activation. These results
      suggest that cannabinoid-induced apoptosis of encephalitogenic T cells may
      cooperate in their anti-inflammatory action in EAE models. The partial
      involvement of CB(2) receptors in WIN-2 action may open new therapeutic doors in
      the management of MS by non-psychoactive selective cannabinoid agonists.

PMID- 17007823
TI  - A rat homologue of CED-6 is expressed in neurons and interacts with clathrin.
AB  - We isolated from a brain library a cDNA encoding an isoform of rat CED-6 that has
      not been previously described. This transcript results from alternative splicing
      of the ced-6 gene present on chromosome 9. We expressed this isoform as his
      tagged protein in E. coli and used the purified protein to raise antibodies to
      investigate the expression of CED-6 in rat brain. Immunoblot analysis showed the
      presence of CED-6 as a doublet of approximately 34 and 33 kDa in cortex,
      hippocampus and cerebellum, indicating that the protein was present in different
      regions of the brain. Subcellular fractionation experiments showed that CED-6
      immunoreactivity did not concentrate in GFAP-containing glial vesicles, whereas
      it showed a distribution similar to the synaptotagmin in synaptosomes-enriched
      fractions, suggesting that CED-6 is present in neurons. CED-6 immunoreactivity
      was also investigated using immunohistochemistry analysis and it was found in
      several brain regions, being particularly strong in the cell body of some groups
      of neurons such as Purkinje cell layer of cerebellum, and pyramidal cells of the
      hippocampal formation and also in epithelial cells from the choroid plexus.
      Importantly, CED-6 immunoreactivity colocalized with a neuronal marker but not
      with a glial marker. Considering that several PTB-containing proteins bind
      clathrin, we investigated whether rat CED-6 would also have this property. Yeast
      two-hybrid and GST pull-down analysis indicated that ratCED-6 interacts with
      clathrin and in cultured cells we detected colocalization between CED-6 and
      clathrin-coated vesicles. The present findings suggest that CED-6 may have a role
      in endocytic trafficking or signaling in neurons.

PMID- 17007822
TI  - Biphasic cytoarchitecture and functional changes in the BBB induced by chronic
      inflammatory pain.
AB  - The blood-brain barrier (BBB) is a dynamic system which maintains brain
      homeostasis and limits CNS penetration via interactions of transmembrane and
      intracellular proteins. Inflammatory pain (IP) is a condition underlying several
      diseases with known BBB perturbations, including stroke, Parkinson's, multiple
      sclerosis and Alzheimer's. Exploring the underlying pathology of chronic IP, we
      demonstrated alterations in BBB paracellular permeability with correlating
      changes in tight junction (TJ) proteins: occludin and claudin-5. The present
      study examines the IP-induced molecular changes leading to a loss in functional
      BBB integrity. IP was induced by injection of Complete Freund's Adjuvant (CFA)
      into the plantar surface of the right hindpaw of female Sprague-Dawley rats.
      Inflammation and hyperalgesia were confirmed, and BBB paracellular permeability
      was assessed by in situ brain perfusion of [14C]sucrose (paracellular diffusion
      marker). The permeability of the BBB was significantly increased at 24 and 72 h
      post-CFA. Analysis of the TJ proteins, which control the paracellular pathway,
      demonstrated decreased claudin-5 expression at 24 h, and an increase at 48 and 72
      h post-injection. Occludin expression was significantly decreased 72 h post-CFA.
      Expression of junction adhesion molecule-1 (JAM-1) increased 48 h and decreased
      by 72 h post-CFA. Confocal microscopy demonstrated continuous expression of both
      occludin and JAM-1, each co-localizing with ZO-1. The increased claudin-5
      expression was not limited to the junction. These results provide evidence that
      chronic IP causes dramatic alterations in specific cytoarchitectural proteins and
      demonstrate alterations in molecular properties during CFA, resulting in
      significant changes in BBB paracellular permeability.

PMID- 17007824
TI  - Synthesis of spacer-containing chlamydial disaccharides as analogues of the alpha
      Kdop-(2-->8)-alpha-Kdop-(2-->4)-alpha-Kdop trisaccharide epitope.
AB  - On the basis of high-resolution crystal structures of the antigen binding
      fragment of the chlamydia-specific monoclonal antibody S25-2 in complex with the
      trisaccharide alpha-Kdop-(2-->8)-alpha-Kdop-(2-->4)-alpha-Kdop and part
      structures thereof, seven modified alpha-Kdop-(2-->8)-alpha-Kdop disaccharide
      derivatives were synthesized starting from the protected disaccharide allyl
      ketoside 1. Hydroboration and subsequent oxidation as well as ozonolysis,
      respectively, followed by Wittig-reaction for chain elongation were used to
      install a terminal carboxylic group on spacer entities of various chain lengths.
      Furthermore, addition of methyl 2-thioacetate to the allyl group furnished the
      corresponding thioether derivative. Standard deprotection gave the target
      disaccharides as simplified trisaccharide analogues, which will be used to probe
      the contribution of the proximal carboxylic group in the binding of chlamydia
      specific di- and trisaccharide-reactive monoclonal antibodies.

PMID- 17007825
TI  - The use of cyclic bifunctional protecting groups in oligosaccharide synthesis--an
      overview.
AB  - A historical overview is presented on stereo-directing effects of cis- and trans
      fused diol protective groups used on both donor and acceptor glycosides.
      Attention is focused on the use of cyclic carbonates and carbamates, diacetals
      and acetals and finally the special case of 1,2-O-orthoesters and 1,2-O
      cyanoalkylidene functionalised residues.

PMID- 17007826
TI  - Intracellular peptides of natriuretic peptide receptor-C inhibit vascular
      hypertrophy via Gqalpha/MAP kinase signaling pathways.
AB  - OBJECTIVE: The present studies were undertaken to investigate if the activation
      of natriuretic peptide receptor-C (NPR-C) that has been shown to inhibit cell
      proliferation could also modulate the hypertrophic responses of vasoactive
      peptides in A10 vascular smooth muscle cells (VSMC). METHODS: For these studies
      A10 VSMC were incubated in the presence of angiotensin II (AngII), endothelin (ET
      1) or arginine vasopressin (AVP) alone or in combination with C-ANP4-23 or NPR-C
      peptides for 24 h and were used for Western blotting and [3H]leucine
      incorporation. The different peptide fragments used were K461KYRITIERRNH472
      (peptide-1) and H481RELREDSIRSH492 (peptide-3) with complete Gi activator
      sequences and R469RNHQEESNIGK480 (peptide-2) and I465TIERRNH472 (peptideY) with
      partial Gi activator sequences. The other peptide used had no structural
      specificity, (Q473EESNIGK480; peptide X) or was the scrambled peptide control for
      peptide-1 (ITIYKKRRNHRE; peptide Z). RESULTS: AngII, ET-1 and AVP significantly
      stimulated protein synthesis in these cells as determined by 3H-leucine
      incorporation, which was inhibited by peptides 1, 2 and 3 and not by peptides X,
      Y or Z in a concentration-dependent manner with an apparent Ki between 1-10 nM.
      In addition, C-ANP4-23 also inhibited protein synthesis stimulated by AngII, ET-1
      and AVP; whereas basal protein synthesis in these cells was not inhibited by C
      ANP4-23 or by the peptide fragments. Furthermore, AngII-, AVP- and ET-1-induced
      stimulation of protein synthesis was inhibited by PD98059 (MEK inhibitor) and
      wortmannin (P13K inhibitor) and this inhibition was potentiated by peptide-1. In
      addition, peptide-1 was also able to inhibit vasoactive peptide-induced
      phosphorylation of ERK1/2 and AKT and enhanced the expression of Gqalpha protein
      in these cells. CONCLUSIONS: These data suggest that C-ANP4-23 and small peptide
      fragments containing 12 amino acids from different regions of cytoplasmic domain
      of NPR-C could modulate vasoactive peptide-stimulated protein synthesis through
      Gqalpha/MAP kinase/P13K and AKT pathways.

PMID- 17007827
TI  - Mortality patterns among industrial workers exposed to chloroprene and other
      substances. II. Mortality in relation to exposure.
AB  - As part of an historical cohort study to investigate the mortality experience of
      industrial workers exposed to chloroprene (CD) and other substances, including
      vinyl chloride monomer (VC), we analyzed mortality from all cancers combined,
      respiratory system (RSC) and liver cancer in relation to CD and VC exposures.
      Subjects were 12,430 workers ever employed at one of two U.S. sites (Louisville,
      KY (n=5507) and Pontchartrain, LA (n=1357)) or two European sites (Maydown,
      Northern Ireland (n=4849) and Grenoble, France (n=717)). Historical exposures for
      individual workers were estimated quantitatively for CD and VC. For sites L, M, P
      and G, respectively, average intensity of CD exposures (median value of exposed
      workers in ppm) were 5.23, 0.16, 0.028 and 0.149 and median cumulative exposures
      (ppm years) were 18.35, 0.084, 0.133 and 1.01. For sites L and M, respectively,
      average intensity of VC exposures (median value of exposed workers in ppm) was
      1.54 and 0.03 and median cumulative exposures (ppm years) were 1.54 and 0.094. We
      performed relative risk (RR) regression modeling to investigate the dependence of
      the internal cohort rates for all cancers combined, RSC and liver cancer on
      combinations of the categorical CD or VC exposure measures with adjustment for
      potential confounding factors. We categorized exposure measures into approximate
      quartiles based on the distribution of deaths from all cancers combined. We also
      considered 5- and 15-year lagged exposure measures and adjusted some RR models
      for worker pay type (white/blue collar) as a rough surrogate for lifetime smoking
      history. All modeling was site-specific to account for exposure heterogeneity. We
      also computed exposure category-specific standardized mortality ratios (SMRs) to
      assess absolute mortality rates. With the exception of a one statistically
      significant association with duration of exposure to CD and all cancers combined
      in plant M, we observed no evidence of a positive association with all cancers,
      RSC or liver cancer and exposure to CD and/or VC using both the unlagged and
      lagged exposure measures: duration, average intensity or cumulative exposure to
      CD or VC; time since first CD or VC exposure; and duration of CD exposure or time
      since first CD exposure in presence or absence of VC exposure. We observed
      elevated and statistically significantly elevated RRs for some analysis
      subgroups, but these were due to inordinately low death rates in the baseline
      categories. With the possible exception of all cancer mortality in plant G, our
      additional adjustment of RRs for pay type revealed no evidence of positive
      confounding by smoking. We conclude that exposures to CD or VC at the levels
      encountered in the four study sites do not elevate mortality risks from all
      cancers, RSC or liver cancer. This conclusion is corroborated by our analysis of
      general mortality patterns among the CD cohort reported in our companion paper
      [G. Marsh, A. Youk, J. Buchanich, M. Cunningham, N. Esmen, T. Hall, M. Phillips,
      Mortality patterns among industrial workers exposed to chloroprene and other
      substances. I. General mortality patterns, Chem.-Biol. Interact., submitted for
      publication].

PMID- 17007828
TI  - Effect of the antibiotic azithromycin on thermotropic behavior of DOPC or DPPC
      bilayers.
AB  - Azithromycin is a macrolide antibiotic known to bind to lipids and to affect
      endocytosis probably by interacting with lipid membranes [Tyteca, D., Schanck,
      A., Dufrene, Y.F., Deleu, M., Courtoy, P.J., Tulkens, P.M., Mingeot-Leclercq,
      M.P., 2003. The macrolide antibiotic azithromycin interacts with lipids and
      affects membrane organization and fluidity: studies on Langmuir-Blodgett
      monolayers, liposomes and J774 macrophages. J. Membr. Biol. 192, 203-215]. In
      this work, we investigate the effect of azithromycin on lipid model membranes
      made of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC). Thermal transitions of both lipids in contact
      with azithromycin are studied by (31)P NMR and DSC on multilamellar vesicles.
      Concerning the DPPC, azithromycin induces a suppression of the pretransition
      whereas a phase separation between the DOPC and the antibiotic is observed. For
      both lipids, the enthalpy associated with the phase transition is strongly
      decreased with azithromycin. Such effects may be due to an increase of the
      available space between hydrophobic chains after insertion of azithromycin in
      lipids. The findings provide a molecular insight of the phase merging of DPPC gel
      in DOPC fluid matrix induced by azithromycin [Berquand, A., Mingeot-Leclercq,
      M.P., Dufrene, Y.F., 2004. Real-time imaging of drug-membrane interactions by
      atomic force microscopy. Biochim. Biophys. Acta 1664, 198-205] and could help to
      a better understanding of azithromycin-cell interaction.

PMID- 17007829
TI  - Two independent origins of Hb Dhonburi (Neapolis) [beta 126 (H4) Val-->Gly]: an
      electrophoretically silent hemoglobin variant.
AB  - BACKGROUND: A beta-hemoglobin variant (beta 126 (H4) Val-->Gly) was reported from
      Thailand and Naples (Southern Italy) as Hb Dhonburi (1) and Hb Neapolis (2),
      respectively. This abnormal hemoglobin, resulting from a valine to glycine
      substitution in the contact region between alpha and beta subunits, gives rise to
      instability at non-physiological conditions. However, it was difficult to
      distinguish this variant from Hb A using hemoglobin electrophoresis and cation
      exchange liquid chromatography. Hb Dhonburi was rarely reported, possibly due to
      a relatively milder phenotype in heterozygote with slightly decreased MCV. Thus
      several Hb Dhonburi carriers might have been under-diagnosed. METHODS: Combined
      molecular analyses by PCR-single strand conformation polymorphism (PCR-SSCP) and
      direct genomic sequencing of the beta globin genes were carried out in 2
      pediatric patients with mild thalassemia intermedia. A novel amplification
      refractory mutation system (ARMS-PCR) was developed and performed in five
      individuals with microcytosis and borderline Hb A(2). RESULTS: Both patients were
      compound heterozygotes for Hb E and Hb Dhonburi. In addition, 5 Hb Dhonburi
      heterozygotes, including 3 identified through thalassemia carrier screening, were
      identified by ARMS-PCR. Linkage analysis of the affected families revealed that
      the haplotype of Hb Dhonburi in Thailand (VII) was different from that of Hb
      Neapolis (V) suggesting 2 independent mutational events. CONCLUSIONS: The
      molecular strategy described provides a robust and economical measure,
      alternative to the whole beta globin genes sequencing, to identify rare or
      unknown beta globin mutations. To overcome its 'silent' nature on
      electrophoresis, we proposed a novel ARMS-PCR for a rapid diagnosis of Hb
      Dhonburi in future cases.

PMID- 17007830
TI  - Impulsive decision-making: learning to gamble wisely?
AB  - A decade ago, Bechara et al. [Bechara, A., Damasio, A. R., Damasio, H., &
      Anderson, S. W. (1994). Insensitivity to future consequences following damage to
      human prefrontal cortex. Cognition, 50, 7-15] published a paper in Cognition,
      introducing a Gambling Task which was designed to mimic everyday decision-making.
      Since then, the task has been computerized, its decision-making components have
      been scrutinized, and it has been employed in various patient groups, such as
      pathological gamblers, substance abusers, and so forth. Time and again it has
      been shown that while normal controls perform well on the task, it is the various
      target populations under scrutiny who exhibit poor performance. Yet, as we show
      in this paper, a total of 46% of normal individuals exhibited poor performance on
      the task, indicating a lack of learning. We argue that while so much importance
      has been placed on contrasting patients with controls, perhaps the real emphasis
      should lie in distinguishing among different individual profiles of performance
      on the task, irrespective of clinical classification. Our basic recommendation is
      to look at the individual data, pool when you can, and only then to contrast
      groups.

PMID- 17007831
TI  - Neurogenin 3 and the enteroendocrine cell lineage in the adult mouse small
      intestinal epithelium.
AB  - It is thought that small intestinal epithelial stem cell progeny, via Notch
      signaling, yield a Hes1-expressing columnar lineage progenitor and an Atoh1 (also
      known as Math1)-expressing common progenitor for all granulocytic lineages
      including enteroendocrine cells, one of the body's largest populations of
      endocrine cells. Because Neurogenin 3 (Neurog3) null mice lack enteroendocrine
      cells, Neurog3-expressing progenitors derived from the common granulocytic
      progenitor are thought to produce the enteroendocrine lineage, although more
      recent work indicates that Neurog3+ progenitors also contribute to non
      enteroendocrine lineages. We aimed to test this model and better characterize the
      progenitors leading from the stem cells to the enteroendocrine lineage. We
      investigated clones derived from enteroendocrine precursors and found no evidence
      of a common granulocytic progenitor that routinely yields all granulocytic
      lineages. Rather, enteroendocrine cells are derived from a short-lived
      bipotential progenitor whose offspring, probably via Notch signaling, yield a
      Neurog3+ cell committed to the enteroendocrine lineage and a progenitor committed
      to the columnar lineage. The Neurog3+ cell population is heterogeneous; only
      about 1/3 are slowly cycling progenitors, the rest are postmitotic cells in early
      stages of enteroendocrine differentiation. No evidence was found that Neurog3+
      cells contribute to non-enteroendocrine lineages. Revised lineage models for the
      small intestinal epithelium are introduced.

PMID- 17007832
TI  - Myogenic regulatory factors Myf5 and Myod function distinctly during craniofacial
      myogenesis of zebrafish.
AB  - The functions of Myf5 and Myod are well known in trunk myogenesis. However, the
      roles that Myf5 and Myod play during craniofacial myogenesis are far from well
      known. We observed that zebrafish myf5 was detected in the primordia of the
      obliques, lateral rectus, sternohyoideus, and pharyngeal mesoderm cores. In
      contrast, myod transcripts were expressed in all head muscle precursors at later
      stages. Knockdown of myf5 revealed that Myf5 was required for the development of
      the obliques, lateral rectus, sternohyoideus, and all pharyngeal muscles, whereas
      knockdown of myod proved that Myod was required for the development of superior
      rectus, medial rectus, inferior rectus, lateral rectus, and the ventral
      pharyngeal muscles. myod mRNA did not rescue the loss of the cranial muscle
      caused by injecting myf5-morpholino, or vice versa, suggesting that the functions
      of Myf5 and Myod were not redundant in head paraxial mesoderm, a finding
      different from their functions in trunk myogenesis. Myf5, but not Myod, was
      required for the forward migration of myf5-positive oblique precursors. All
      evidences reveal that Myf5 and Myod function independently during cranial
      myogenesis. On the basis of the expression patterns of myf5 and myod, we propose
      a model to present how Myf5 and Myod are involved in head myogenesis of
      zebrafish.

PMID- 17007833
TI  - A database of mRNA expression patterns for the sea urchin embryo.
AB  - We present an initial characterization of a database that contains temporal
      expression profiles of sequences found in 35,282 gene predictions within the sea
      urchin genome. The relative RNA abundance for each sequence was determined at 5
      key stages of development using high-density oligonucleotide microarrays that
      were hybridized with populations of polyA+ RNA sequence. These stages were two
      cell, which represents maternal RNA, early blastula, the time at which major
      tissue territories are specified, early and late gastrula, during which important
      morphogenetic events occur, and the pluteus larva, which marks the culmination of
      pre-feeding embryogenesis. We provide evidence that the microarray reliably
      reports the temporal profiles for the large majority of predicted genes, as shown
      by comparison to data for many genes with known expression patterns. The
      sensitivity of this assay allows detection of mRNAs whose concentration is only
      several hundred copies/embryo. The temporal expression profiles indicate that 5%
      of the gene predictions encode mRNAs that are found only in the maternal
      population while 24% are embryo-specific. Further, we find that the concentration
      of >80% of different mRNAs is modulated by more than a factor of 3 during
      development. Along with the annotated sea urchin genome sequence and the whole
      genome tiling array (the transcriptome, Samanta, M., Tongprasit, W., Istrrail,
      S., Cameron, R., Tu, Q., Davidson, E., Stolc, V., in press. A high-resolution
      transcriptome map of the sea urchin embryo. Science), this database proves a
      valuable resource for designing experiments to test the function of specific
      genes during development.

PMID- 17007834
TI  - The mutagenic hazards of environmental PM2.5 in Turin.
AB  - Owing to the large number of natural and anthropogenic sources, particulate
      matter (PM) may present several physical and chemical patterns in different
      areas. The finer PM2.5 fraction, which is now widely but not routinely measured
      in Europe, is considered to be the alveolar fraction of the ambient particles.
      Annual and winter mean concentrations of PM2.5 substantially vary in Europe, with
      higher concentrations in the South. The aims of this work were to (a) measure the
      PM2.5 levels in Turin over a long period, (b) evaluate mutagenic activities of
      organic extracts containing this collected complex mixture using the Ames test
      and (c) determine the level of polycyclic aromatic hydrocarbons (PAHs) in order
      to identify important mutagens in ambient air. Sampling was carried out from
      November 2001 to December 2004. The monthly mean of PM2.5 was 48.76+/-24.12
      microg/m3. From the beginning to the end of the sample period there was a
      decrease in gravimetric levels, with annual means of 54.10+/-29.77 microg/m3 in
      2002; 42.48+/-15.73 microg/m3 in 2003 and 45.89+/-24.92 microg/m3 in 2004.
      Samples were tested for mutagenicity using Salmonella typhimurium strains TA98
      and TA100, with and without S9 mix metabolic activation. A positive genotoxic
      response was observed for TA98, with and without metabolic activation. The
      measured PAHs monthly mean level was 8.24+/-6.30 ng/m3, with values ranging from
      0.20 to 21.38 ng/m3 Seasonal variation of gravimetric, mutagenic and PAH values
      was significant. The Salmonella assay results statistically correlated to PM2.5
      and PAHs levels, but sometimes the mutagenic potencies were rather different
      despite an equal concentration of pollutant. The results confirm the usefulness
      of this biological approach to detect genotoxic properties of sampled PM2.5 and
      they show the variability of the mutagenic properties of the airborne mixture
      over time.

PMID- 17007835
TI  - Requirement for JNK-dependent upregulation of BimL in anti-IgM-induced apoptosis
      in murine B lymphoma cell lines WEHI-231 and CH31.
AB  - The cross-linking of B cell receptor (BCR) undergoes growth arrest, accompanied
      by apoptosis, in the CH31 and WEHI-231 B lymphoma cells, a model representing
      primary immature B cells. We have previously demonstrated that sustained
      activation of c-Jun N-terminal kinase (JNK) is required for BCR-mediated
      apoptosis. In the present study, we examined how the anti-IgM-induced prolonged
      activation of JNK results in apoptosis. Anti-IgM upregulated the expression
      levels of three isoforms of Bim protein, especially BimL, which appeared to be
      dependent on JNK activation. In contrast to protein expression, BimL mRNA levels
      were down-regulated upon anti-IgM stimulation, suggesting that anti-IgM-induced
      upregulation of BimL is regulated through post-transcriptional control. Upon JNK
      activation, phosphorylated form of JNK, together with Bax migrated from cytosol
      to mitochondria. In unstimulated cells, BimL protein was complexed with Bcl-x(L)
      and changed the partner to associate with Bax on the mitochondrial membrane after
      ligation of BCR, leading to initiation of apoptotic processes. Retroviral
      transduction of BimL into WEHI-231 cells overexpressing dominant-negative form of
      JNK1 (dnJNK1) resulted in a comparable level of apoptotic cells to control cells,
      whereas the BimL-mediated apoptosis was partially prevented by Bcl-x(L). Taken
      together, engagement of BCR with anti-IgM results in association of Bax-alpha
      with BimL in the mitochondria, at least in part, through a sustained activation
      of JNK.

PMID- 17007836
TI  - Macroglial and retinal changes in hypercholesterolemic rabbits after
      normalization of cholesterol levels.
AB  - This study evaluates hypercholesterolemic rabbits, examining the retinal changes
      in Muller cells and astrocytes as well as their variations after a period of
      normal blood-cholesterol values induced by a standard diet. New Zealand rabbits
      were divided into three groups: G0, fed a standard diet; G1A, fed a 0.5%
      cholesterol-enriched diet for 8 months; and G1B, fed as G1A followed by standard
      diet for 6 months. Eyes were processed for transmission electron microscopy and
      immunohistochemistry (GFAP). While G1B resembled G0 more than did G1A, they
      shared alterations with G1A: a) as in G1A, Muller cells were GFAP+, filled spaces
      left by axonal degeneration, formed glial scars and their nuclei were displaced
      to the nerve-fibre layer. The area occupied by the astrocytes associated with the
      nerve-fibre bundles (AANFB) and by perivascular astrocytes (PVA) in G1A and G1B
      was significantly lower than in controls. However, no significant differences in
      PVA were found between G1A and G1B. In G1B, type I PVA was absent and replaced by
      hypertrophic type II cells; b) Bruch's membrane (BM) was thinner in G1B than in
      G1A; c) the retinal pigment epithelium (RPE) cytoplasm contained fewer lipids in
      G1B than in G1A; d) in G1A and G1B choriocapillaris and retinal vessel showed
      alterations with respect to G0; e) cell death and axonal degeneration in the
      retina were similar in G1A and G1B. The substitution of a hyperlipemic diet by a
      standard one normalizes blood-lipid levels. However, the persistence of damage at
      retinal vessels and BM-RPE could trigger chronic ischemia.

PMID- 17007838
TI  - Recombinant adenovirus vector-mediated functional expression of neurotropin-3
      receptor (TrkC) in neural stem cells.
AB  - We have constructed a recombinant adenovirus expression vector carrying the human
      neurotrophin-3 (NT-3) receptor TrkC (tyrosine protein kinase C) gene (rAd-TrkC;
      2478 bp) and confirmed the expression of the encoded TrkC in green fluorescent
      protein (GFP)-murine neural stem cells (NSCs) by reverse transcription polymerase
      chain reaction (RT-PCR), Western blot analysis, and immunocytochemistry. The
      activity of the expressed rAd-TrkC was verified in vitro by evaluating dose
      related responses of NSCs to NT-3, a TrkC specific ligand. TrkC-GFP-NSCs had a
      significantly higher percentage of neuronal differentiation when treated with NT
      3 relative to the rAd-LacZ control cells (55.2% vs. 29.8%; P<0.05, chi(2) test).
      Thus, our rAd-TrkC vector can transfect NSCs and produce functional TrkC
      receptors to promote neuronal differentiation of NSCs.

PMID- 17007837
TI  - Apolipoprotein E alleles can contribute to the pathogenesis of numerous clinical
      conditions including HSV-1 corneal disease.
AB  - Apolipoprotein E (ApoE) alleles have been reported to affect the clinical outcome
      of numerous cardiovascular, neurodegenerative, and viral infectious diseases,
      including atherosclerosis, Alzheimer's disease (AD), hepatitis C, and HIV. The
      major alleles of ApoE are 2, 3, and 4. ApoE genotypes have been hypothesized to
      regulate many biological functions, resulting in significant changes in the onset
      and/or outcome (severity and duration) of several clinical conditions. Based on
      genetic analyses in human and animal studies using knockout (ApoE -/-) mice and
      mice transgenic for human 3 and 4, we present evidence that strongly suggests
      that the ApoE alleles can regulate the pathogenesis of ocular herpes simplex
      virus type 1 (HSV-1) infections. This review will summarize the major studies
      that support this hypothesis. Significant gender based differences in HSV-1
      pathogenesis have also been reported, suggesting that hormonal regulation
      combined with ApoE genotype plays a significant role in HSV-1 pathogenesis.
      Identification of specific mechanisms in ocular HSV-1 infections related to the
      ApoE alleles and gender could lead to therapeutic intervention based on the
      properties of the apoE isoforms. While many clinical investigations have been
      reported and, to a lesser extent, transgenic mouse studies have been conducted,
      no specific mechanisms of how ApoE induces or alters clinical disease are known.

PMID- 17007839
TI  - Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)
      induced cognitive deficits in mice.
AB  - Consumption of caffeine, an adenosine receptor antagonist, was found to be
      inversely associated with the incidence of Alzheimer's disease. Moreover,
      caffeine protects cultured neurons against beta-amyloid-induced toxicity, an
      effect mimicked by adenosine A(2A) but not A(1) receptor antagonists. We now
      tested if caffeine administration would prevent beta-amyloid-induced cognitive
      impairment in mice and if this was mimicked by A(2A) receptor blockade. One week
      after icv administration of the 25-35 fragment of beta-amyloid (Abeta, 3 nmol),
      mice displayed impaired performance in both inhibitory avoidance and spontaneous
      alternation tests. Prolonged treatment with caffeine (1 mg/ml) had no effect
      alone but prevented the Abeta-induced cognitive impairment in both tasks when
      associated with acute caffeine (30 mg/kg) 30 min treatment before Abeta
      administration. The same protective effect was observed after subchronic (4 days)
      treatment with daily injections of either caffeine (30 mg/kg) or the selective
      adenosine A(2A) receptor antagonist SCH58261 (0.5 mg/kg). This provides the first
      direct in vivo evidence that caffeine and A(2A) receptor antagonists afford a
      protection against Abeta-induced amnesia, which prompts their interest for
      managing Alzheimer's disease.

PMID- 17007840
TI  - Audiogenic seizure susceptibility is reduced in fragile X knockout mice after
      introduction of FMR1 transgenes.
AB  - The Fmr1 knockout (KO) mouse is characterized by an increased audiogenic seizure
      (AGS) susceptibility and is considered a good animal model for epilepsy and
      seizures in the human fragile-X (FRAX) syndrome. Here, we tested the hypothesis
      that the reintroduction of the FMR1 gene is able to revert the AGS susceptibility
      characterizing Fmr1 KO mice. To this aim, two groups of Fmr1 KO transgenic mice,
      which have additional copies of the human FMR1 gene (YAC) or FMR1 cDNA (G6) were
      used. AGS susceptibility of these mice was examined and compared to that of Fmr1
      KO, wild type, and wild-type animals in whom the FMR1gene was also introduced
      (over-expressed). Mice were tested at different ages because AGS susceptibility
      is age dependent. The intensity of response was scored and the results were
      analyzed by means of 2-way analysis of variance to evaluate the effects of age
      and genetic condition. We found that AGS susceptibility rescue is complete in the
      G6 mice and partial in YAC mice. Our data indicate that the introduction of the
      human FMR1 gene in Fmr1 KO mice is able to revert the Fmr1 KO epileptic
      phenotype.

PMID- 17007841
TI  - Analysis of detergent-resistant membranes associated with apical and basolateral
      GPI-anchored proteins in polarized epithelial cells.
AB  - Detergent-resistant membranes (DRMs) represent specialized membrane domains
      resistant to detergent extraction, which may serve to segregate proteins in a
      specific environment in order to improve their function. Segregation of
      glycosylphosphatidylinositol-anchored proteins (GPI-APs) in DRMs has been shown
      to be involved in their sorting to the apical membrane in polarized epithelial
      cells. Nonetheless, we have shown that both apical and basolateral GPI-APs
      associate with DRMs. In this report we investigated the lipid composition of DRMs
      associated with an apical and a basolateral GPI-AP. We found that apical and
      basolateral DRMs contain the same lipid species although in different ratios.
      This specific lipid ratio is maintained after mixing the cells before lysis
      indicating that DRMs maintain their identity after Triton extraction.

PMID- 17007842
TI  - Transcriptome changes in a colon adenocarcinoma cell line in response to
      photochemical treatment as used in photochemical internalisation (PCI).
AB  - The photochemical internalisation (PCI) technology liberates endocytosed
      macromolecules like transgenes from endocytic vesicles in response to
      photochemical treatment. Thereby PCI improves gene transfection and is suggested
      for use in gene therapy. It has been proposed that PCI might also stimulate
      transcription of internalised transgenes, especially if they are controlled by
      photochemically inducible promoters (transcriptional targeting). In order to
      identify inducible promoters, and to evaluate the treatments influence on
      cellular transcriptional activity, the effect of the photochemical treatment as
      used in PCI (with the photosensitizer disulfonated meso-tetraphenylporphin
      followed by illumination) on gene transcription in WiDr adenocarcinoma cells was
      evaluated using microarrays. The expression of 390 genes were identified
      significantly changed (89% were up-regulated), of which genes associated with DNA
      binding and transcriptional functions were the most represented. This may be
      important for the expression of a photochemically internalised transgene under a
      specific promoter control. Real-time PCR verified photochemical up-regulation of
      the HSP family genes, as well as down-regulation of EGR-1 at 2-10h post
      treatment, suggesting that the HSP (particularly HSP70), in addition to the
      microarray-identified metallothioneins, but not the EGR-1 promoters, could be
      relevant promoter candidates for transcriptional targeting via PCI. The resulting
      overview of gene expression changes in WiDr cells exposed to the PCI-relevant
      photochemical treatment also provide a basis for the design of new PCI-based
      strategies with respect of transcriptional targeting.

PMID- 17007843
TI  - Molecular characterization of the hypothetical 66.3-kDa protein in mouse:
      lysosomal targeting, glycosylation, processing and tissue distribution.
AB  - Recently, we and others identified the 66.3-kDa protein as one of several
      putative novel lysosomal matrix proteins by analyzing mannose 6-phosphate
      receptors binding proteins [Kollmann K., Mutenda K.E., Balleininger M., Eckermann
      E., von Figura K., Schmidt B., Lubke T. (2005) Identification of novel lysosomal
      matrix proteins by proteome analysis. Proteomics 5(15), 3966-3678, Sleat D.E.,
      Lackland H., Wang Y., Sohar I., Xiao G., Li H., Lobel P. (2005) The human brain
      mannose 6-phosphate glycoproteome: a complex mixture composed of multiple
      isoforms of many soluble lysosomal proteins. Proteomics. 5(6), 1520-1532]. Here,
      we describe the expression of the mouse 66.3-kDa protein in HT1080 cells in which
      it is synthesized as a precursor of about 75kDa and subsequently processed by
      limited proteolysis to mature polypeptides accumulating in the lysosomal
      compartment. The lysosomal localisation of the endogenous 66.3-kDa protein was
      verified by indirect immunofluorescence in mouse embryonic fibroblasts and by
      subcellular fractionation of tyloxapol-filled mouse liver lysosomes. Northern
      blot analysis reveals high transcriptional levels in testis, liver and kidney,
      whereas Western blot analysis shows high protein levels in brain, heart, lung and
      spleen. Interestingly, in mouse the endogenous 66.3-kDa protein is processed in a
      highly tissue-dependent manner to mature forms.

PMID- 17007844
TI  - Observation of single-stranded DNA on mica and highly oriented pyrolytic graphite
      by atomic force microscopy.
AB  - Atomic force microscopy was used to image single-stranded DNA (ssDNA) adsorbed on
      mica modified by Mg(2+), by 3-aminopropyltriethoxysilane or on modified highly
      oriented pyrolytic graphite (HOPG). ssDNA molecules on mica have compact
      structures with lumps, loops and super twisting, while on modified HOPG graphite
      ssDNA molecules adopt a conformation without secondary structures. We have shown
      that the immobilization of ssDNA under standard conditions on modified HOPG
      eliminates intramolecular base-pairing, thus this method could be important for
      studying certain processes involving ssDNA in more details.

PMID- 17007845
TI  - Plant mitochondrial genes can be expressed from mRNAs lacking stop codons.
AB  - The mRNAs of the nad6 and ccmC genes of Arabidopsis and cauliflower were found to
      be processed upstream of the inframe stop codons. This result was confirmed by
      northern hybridization and by RT-PCR. There is no evidence that an alternative
      stop codon is created post-transcriptionally, either by RNA editing or by
      polyadenylation. The non-stop mRNAs are found in the high molecular weight
      polysomal fractions, suggesting that they are translated. Using antibodies
      directed against CcmC, the corresponding protein was detected in Arabidopsis
      mitochondrial extracts. These observations raise the question of how the plant
      mitochondrial translation system deals with non-stop mRNAs.

PMID- 17007846
TI  - Defining residues involved in human rhinovirus 2A proteinase substrate
      recognition.
AB  - The 2A proteinase (2A(pro)) of human rhinoviruses (HRVs) initiates proteolytic
      processing by cleaving between the C-terminus of VP1 and its own N-terminus. It
      subsequently cleaves the host protein eIF4GI. HRV2 and HRV14 2A(pro) cleave at
      IITTA *GPSD and DIKSY *GLGP on their respective polyproteins. The HRV2 2A(pro)
      cleavage site on eIF4GI is TLSTR *GPPR. We show that HRV2 2A(pro) can self
      process at the eIF4GI cleavage sequence whereas HRV14 2A(pro) cannot, due to the
      presence of the arginine residue at P1. The mutations A104C or A104S in HRV14
      2A(pro) restored cleavage when arginine was present at P1, although not to wild
      type levels. These experiments define residues which determine substrate
      recognition in rhinoviral 2A(pro).

PMID- 17007847
TI  - Is the addition of metformin efficacious in the treatment of clomiphene citrate
      resistant patients with polycystic ovary syndrome? A structured literature
      review.
AB  - OBJECTIVE: The aim of this literature search is to establish if metformin is
      efficacious when given to clomiphene citrate (CC)-resistant polycystic ovary
      syndrome (PCOS) patients. DESIGN: Medline database was searched from 1 January
      1980 to 1 January 2005. Inclusion criteria were prospective randomized control
      trials where metformin was randomized either with placebo or CC to induce
      ovulation in the CC-resistant patient. RESULT(S): Group 1: Four trials were
      prospective double-blind placebo controlled. When the data of the four trials
      were pooled, the overall effect of the addition of metformin in the CC patient
      was P=.0006 with a 95% confidence interval (CI) of odds ratio (OR) 1.81-8.84.
      Group 2: In two trials the randomization was only prospective. When the data of
      these two trials were pooled, the overall effect of the addition of metformin in
      the CC-resistant patient was P<.0001 with a 95% CI of OR 6.24-70.27. Groups 1 and
      2: The combined data show an overall effect of P<.0001 with a 95% CI of OR 3.59
      12.96. CONCLUSION(S): The addition of metformin in the CC-resistant patient is
      highly effective in achieving ovulation induction.

PMID- 17007848
TI  - Select patients with hypogonadotropic hypogonadism may respond to treatment with
      clomiphene citrate.
AB  - OBJECTIVE: To review the management of male hypogonadotropic hypogonadism (HH)
      and evaluate the efficacy of clomiphene citrate (CC). DESIGN: Retrospective
      review. SETTING: Two university-based urology clinics. PATIENT(S): Ten patients
      referred for male infertility evaluation. INTERVENTION(S): Patients were treated
      with either clomiphene citrate or injectable gonadotropins. MAIN OUTCOME
      MEASURE(S): Changes in seminal parameters, gonadotropin levels, serum
      testosterone, and pregnancy. RESULT(S): Ten men who were evaluated for
      infertility were diagnosed with HH. Four had Kallmann's syndrome, four idiopathic
      HH, and two panhypopituitarism. Eight patients were azoospermic, and two were
      oligospermic on presentation. Three of the four men with adult-onset idiopathic
      HH responded to CC alone with increases in testosterone, FSH, and LH. Semen
      parameters in this group also improved, and two of the three men achieved
      pregnancies with CC alone. Out of the ten men actively attempting conception,
      four pregnancies were achieved. Three pregnancies (two with CC and one with
      gonadotropins) were in men diagnosed with adult-onset idiopathic forms of HH.
      CONCLUSION(S): Select patients with adult-onset idiopathic forms of HH may
      benefit from a trial of clomiphene citrate.

PMID- 17007849
TI  - A prospective randomized trial comparing anastrozole and clomiphene citrate in an
      ovulation induction protocol using gonadotropins.
AB  - OBJECTIVE: To compare the ovarian and endometrial effects of anastrozole and
      clomiphene when used with gonadotropins in a combination protocol. DESIGN:
      Prospective randomized trial. SETTING: Academic infertility center. PATIENT(S):
      Fifty infertile women. INTERVENTIONS(S): Women were randomized to receive either
      1 mg anastrozole or 100 mg clomiphene citrate for 5 days (cycle days 3-7)
      followed by FSH injections (days 7-11) for ovulation induction. A subset
      participated in a crossover arm of the study. MAIN OUTCOME MEASURE(S): Ovarian
      follicle number and size, E(2) levels, endometrial thickness, pregnancy, and
      cancellation rates. RESULT(S): On cycle day 12, anastrozole cycles were
      associated with fewer total follicles (1.4 vs. 3.6, P=0.01), fewer mature
      follicles (0.6 vs. 1.6, P<.01), lower serum E(2) (131 pg/mL vs. 613 pg/mL,
      P<.01,) and the same endometrial stripe thickness compared with clomiphene
      citrate cycles. Cycle cancellation rates were similar between the two groups. On
      the day of hCG administration in noncancelled cycles, anastrozole cycles were
      associated with fewer total follicles (1.6 vs. 3.8, P<.01), fewer mature
      follicles (1.3 vs. 2.1, P<.01), and an equal endometrial stripe thickness
      compared with clomiphene citrate cycles. Pregnancy rates were similar between
      clomiphene (20%) and anastrozole (12%) cycles. CONCLUSION(S): Anastrozole when
      used in conjunction with gonadotropins results in lower E(2) levels and fewer
      follicles than clomiphene citrate. A combination protocol of anastrozole and
      gonadotropins may be a safer protocol for patients at higher risk of
      hyperstimulation and multiple births after infertility treatments.

PMID- 17007850
TI  - A prospective evaluation of uterine abnormalities by saline infusion
      sonohysterography in 1,009 women with infertility or abnormal uterine bleeding.
AB  - OBJECTIVE: To evaluate the role of saline infusion sonohysterography (SIS) in the
      investigation of uterine abnormalities and malformations in patients referred for
      infertility work-up compared with women with abnormal uterine bleeding (AUB).
      DESIGN: Prospective cohort study. SETTING: Academically oriented private
      practice. PATIENT(S): One thousand nine consecutive women examined by SIS for
      infertility work-up (n = 600, infertility group) or AUB investigation (n = 409,
      AUB group). INTERVENTION(S): SIS. MAIN OUTCOME MEASURE(S): Intracavitary
      abnormalities and uterine anomalies. RESULT(S): Among the women in the
      infertility group, 16.2% (n = 97) were found to have intracavitary abnormalities,
      including polyps (13.0%), submucous fibroids (2.8%), and adhesions (0.3%).
      Significantly, more patients in the AUB group (39.6%, n = 162) revealed
      intracavitary abnormalities, including polyps (29.8%), submucous fibroids (9.0%),
      and adhesions (0.7%). In contrast, significantly more uterine anomalies were
      found in the infertility group (20%, n = 120) compared with the AUB group (9.5%,
      n = 39). Arcuate uterus was the most common finding (15% vs. 6.4% of patients,
      respectively). CONCLUSION(S): An SIS procedure for infertility work-up revealed a
      substantial percentage of infertile patients with intracavitary abnormalities and
      uterine anomalies. Because the technique is safe, well tolerated, and feasible in
      an outpatient setting, SIS should be considered routinely in the early stage of
      infertility and AUB investigation.

PMID- 17007851
TI  - Conservative management of placenta increta with selective arterial embolization
      preserves future fertility and results in a favorable outcome in subsequent
      pregnancies.
AB  - OBJECTIVE: To present a case of selective arterial embolization for the treatment
      of placenta increta in a patient with subsequent pregnancy. DESIGN: Case report
      and literature review. SETTING: Community-based hospital. PATIENT(S): A 31-year
      old G2P1 woman with placenta increta presenting with delayed postpartum
      hemorrhage. INTERVENTION(S): Selective uterine artery embolization. MAIN OUTCOME
      MEASURE(S): Cessation of uterine hemorrhage, future pregnancy. RESULT(S): The
      patient's uterine bleeding immediately resolved. She subsequently delivered a
      healthy neonate at term without recurrence of abnormal placentation.
      CONCLUSION(S): Arterial embolization is effective for treating placenta increta
      in women who wish to preserve fertility. A review of the literature demonstrates
      a 76.9% success rate and an 11% complication rate.

PMID- 17007852
TI  - Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating
      endometriosis.
AB  - OBJECTIVE: To detect and quantify mast cells in peritoneal, ovarian, and deep
      infiltrating endometriosis and to study the relationship between mast cells and
      nerves in endometriosis. DESIGN: Prospective histological and immunohistochemical
      study. SETTING: University of Brussels, Belgium. PATIENT(S): Sixty-nine women
      undergoing laparoscopic excision of endometriosis for pain. Thirty-seven biopsies
      of normal tissue were obtained from women without endometriosis. INTERVENTION(S):
      Excision of endometriosis from different anatomical locations. MAIN OUTCOME
      MEASURE(S): Immunohistochemistry with chymase and tryptase to confirm the
      presence of mast cells and activated mast cells, respectively, in endometriotic
      lesions. Quantification of mast cells, activated mast cells, and degranulating
      mast cells in the different locations of endometriosis. Study of the relationship
      between mast cells and nerves by quantifying mast cells located less than 25 mum
      from nerves immunohistochemically stained with S-100 protein. Preoperative pain
      score evaluation by visual analogue scales. RESULT(S): Patients with deeply
      infiltrating lesions had significantly higher preoperative pain scores than
      patients with peritoneal or ovarian endometriosis. Mast cells and degranulating
      mast cells are significantly more abundant in endometriotic lesions than in
      nonaffected tissues. Deep infiltrating lesions show a significantly higher number
      of mast cells, activated mast cells, and mast cells located <25 microm from
      nerves than peritoneal and ovarian lesions. We found significantly more
      degranulating mast cells in deep infiltrating lesions than in peritoneal lesions.
      CONCLUSION(S): The presence of increased activated and degranulating mast cells
      in deeply infiltrating endometriosis, which are the most painful lesions, and the
      close histological relationship between mast cells and nerves strongly suggest
      that mast cells could contribute to the development of pain and hyperalgesia in
      endometriosis, possibly by a direct effect on nerve structures.

PMID- 17007853
TI  - Effect of the copper-intrauterine device (TCu 380A) on subendometrial
      microvascularization and uterine artery blood flow.
AB  - During this cohort study, the copper-intrauterine device (IUD) did not modify
      subendometrial microvascularization. However, subendometrial blood flow increased
      in patients who experienced IUD-induced side effects.

PMID- 17007854
TI  - Expression and immunolocalization of the mu-opioid receptor in human sperm cells.
AB  - The expression of the mu-opioid receptor in human sperm cells was investigated by
      immunocytochemistry and immunoblot analyses. Results demonstrated that the
      receptor is localized on the acrosomal region and the neck portion of the sperm
      head. These results suggest a possible role for the mu-opioid receptor in
      mediating the action of endogenous opioid peptides on sperm cells during the
      complex and poorly characterized cellular events that enable spermatozoa to
      fertilize oocytes.

PMID- 17007855
TI  - Expression of the HSPA2 gene in ejaculated spermatozoa from adolescents with and
      without varicocele.
AB  - OBJECTIVE: To evaluate mRNA expression of the HSPA2 gene in ejaculated
      spermatozoa in adolescents with and without varicocele. DESIGN: Controlled
      prospective study. SETTING: Patients in an academic research environment.
      PATIENTS: Adolescent patients with clinical diagnosed bilateral varicocele grades
      II and III, and adolescent patients without varicocele. INTERVENTION: Reverse
      transcription-polymerase chain reaction (RT-PCR) analysis of HSPA2 gene
      expression in adolescents with and without varicocele. MAIN OUTCOME MEASURE:
      Comparative RT-PCR expression analysis of HSPA2 gene mRNA, compared to the
      housekeeping beta-actin gene. RESULTS: Sperm from adolescents with varicocele and
      oligozoospermia had significantly lower levels of HSPA2 gene expression than both
      adolescents without varicocele (controls) and adolescents with varicocele and
      normal sperm concentration (P<.05). The latter group had a nonsignificant
      increase in gene expression compared to the control group. CONCLUSIONS: This is
      the first report on HSPA2 gene expression in ejaculated spermatozoa from
      adolescents and its relationship with varicocele pathology. Results demonstrated
      that HSPA2 expression was down-regulated in adolescents with varicocele and
      oligozoospermia compared to controls. There was a higher, albeit nonsignificant,
      gene expression in adolescents with varicocele and normal sperm concentration
      than in controls. We speculate that expression levels of this gene might be used
      as a molecular marker for the acquisition of thermal tolerance in ejaculated
      spermatozoa.

PMID- 17007856
TI  - Social environment regulates corticotropin releasing factor, corticosterone and
      vasopressin in juvenile prairie voles.
AB  - Stressful social conditions, such as isolation, that occur during sensitive
      developmental periods may alter present and future social behavior. Changes in
      the neuroendocrine mechanisms closely associated with affiliative behaviors and
      stress reactivity are likely to underlie these changes in behavior. In the
      present study, we assessed the effects of post-weaning social housing conditions
      on the neuropeptides arginine vasopressin (AVP) and oxytocin (OT), and components
      of the hypothalamic-pituitary-adrenal axis (corticotropin releasing factor:
      [CRF], and corticosterone: [CORT]) in the prairie vole (Microtus ochrogaster), a
      socially monogamous bi-parental rodent. Following weaning at 21 days of age,
      prairie voles were maintained in one of three housing conditions: social
      isolation (isolate), paired with a same sex sibling (sibling) or paired with a
      stranger (stranger) of the same sex and age. Housing conditions were maintained
      for either 4 or 21 days. Central CRF, AVP and OT immunoreactivity (ir) were
      quantified and circulating plasma CORT, AVP and OT were assayed. Isolated voles
      had higher CRF-ir in the paraventricular nucleus of the hypothalamus (PVN)
      compared with sibling and stranger housed voles. Plasma CORT was significantly
      higher in isolates. AVP-ir was significantly lower in the PVN of isolate females
      compared to either sibling females or stranger females. However, AVP-ir was
      significantly higher in the supraoptic nucleus (SON) of isolates compared to
      siblings. There were no differences in central OT-ir or plasma OT. These results
      identify neuroendocrine mechanisms which respond to isolation and potentially
      modulate behavior.

PMID- 17007857
TI  - Pre-pregnancy body mass index and pregnancy outcomes.
AB  - OBJECTIVE: To determine the effect of maternal pre-pregnancy BMI on pregnancy
      outcomes. METHODS: Pregnancy cohort recruited pregnancies between 16 and 18
      weeks. BMI evaluated underweight, BMI<18.5, normal, BMI 18.5-25, overweight BMI
      25-30, and obese BMI>30 women. RESULTS: Pre-pregnancy BMI classified 331 women as
      underweight (11.7%), 1982 normal (69.9%), 326 overweight (11.5%), and 188 as
      obese (6.6%). Obese women were more likely to develop gestational diabetes
      (p<0.001), hypertension (p<0.001), preeclampsia (p<0.001), need labor induction
      (p<0.001), cesarean delivery for fetal distress (p<0.001), postpartum hemorrhage
      (p=0.003), need neonatal resuscitation (p=0.001) and deliver hypoglycemic infants
      (p=0.007). Being underweight is correlated with fetal growth restriction
      (p=0.001). CONCLUSION: Pre-pregnancy obesity is a risk factor for gestational
      diabetes, preeclampsia, labor induction, cesarean for fetal distress, postpartum
      hemorrhage and neonatal hypoglycemic and need for resuscitation. Being
      underweight is risk factor for fetal growth restriction.

PMID- 17007858
TI  - Red clover extract (MF11RCE) supplementation and postmenopausal vaginal and
      sexual health.

PMID- 17007859
TI  - Serious mental illness and physical health problems: a discussion paper.
AB  - People with serious mental illness have higher morbidity and mortality rates of
      chronic diseases than the general population. This discussion paper explores the
      complex reasons for these disparities in health, such as limitations of health
      services, the effects of having a serious mental illness, health behaviours and
      the effects of psychotropic medication. Physical health can be enhanced by
      improved monitoring and lifestyle interventions initiated at the start of
      treatment. There are opportunities for mental health nurses to play a significant
      role in improving both the physical and mental health of people with serious
      mental illness.

PMID- 17007860
TI  - Comparative analysis of the excretory-secretory proteome of the muscle larva of
      Trichinella pseudospiralis and Trichinella spiralis.
AB  - The nematodes Trichinella spiralis and Trichinella pseudospiralis are both
      intracellular parasites of skeletal muscle cells and induce profound alterations
      in the host cell resulting in a re-alignment of muscle-specific gene expression.
      While T. spiralis induces the production of a collagen capsule surrounding the
      host-parasite complex, T. pseudospiralis exists in a non-encapsulated form and is
      also characterised by suppression of the host inflammatory response in the
      muscle. These observed differences between the two species are thought to be due
      to variation in the proteins excreted or secreted (ES proteins) by the muscle
      larva. In this study, we use a global proteomics approach to compare the ES
      protein profiles from both species and to identify individual T. pseudospiralis
      proteins that complement earlier studies with T. spiralis. Following two
      dimensional gel electrophoresis, tandem mass spectrometry was used to identify
      the peptide spots. In many cases identification was aided by the determination of
      partial peptide sequence from selected mass ions. The T. pseudospiralis spots
      identified included the major secreted glycoproteins and the secreted 5'
      nucleotidase. Furthermore, two major groups of T. spiralis-specific proteins and
      several T. pseudospiralis-specific proteins were identified. Our results
      demonstrate the value of proteomics as a tool for the identification of ES
      proteins that are differentially expressed between Trichinella species and as an
      aid to identifying key parasite proteins that are involved in the host-parasite
      interaction. The value of this approach will be further enhanced by data arising
      out the current T. spiralis genome sequencing project.

PMID- 17007861
TI  - Beneficial effect of statins in multiple sclerosis: is it dose-dependent?

PMID- 17007862
TI  - Optical coherence tomography accurately identifies intermediate atherosclerotic
      lesions--an in vivo evaluation in the rabbit carotid artery.
AB  - OBJECTIVE: We tested the ability of optical coherence tomography (OCT) to
      identify very early stages of atherosclerosis in vivo. METHODS: Twelve New
      Zealand white male rabbits (weight 3.5-4.0 kg) underwent perivascular electrical
      injury of the common carotid arteries, and were then fed a cholesterol-rich diet.
      At 43+/-16 (range 27-63) days after injury, arteries were imaged by OCT, then
      rabbits were euthanized and vessels processed for histology. RESULTS: A total of
      14 carotid arteries were imaged by OCT and histology; 22 atherosclerotic lesions
      were identified, 16 (73%) occurring at the site of the electrical injury. At
      histology, 4 lesions were defined as Stary type I (isolated macrophages), 8 as
      type II (intracellular lipid accumulations), and 10 as type III (small
      extracellular lipid pools). No advanced (> or =type IV) lesions were documented.
      OCT failed to detect any type I lesions, but correctly defined a minority (2/8,
      25%) of type II lesions and the majority (8/10, 80%) of type III lesions. For
      type III lesions, sensitivity, specificity and diagnostic accuracy of OCT were
      80%, 95%, and 95%, respectively. CONCLUSIONS: OCT can accurately detect
      intermediate (type-III) atherosclerotic lesions in vivo, but still fails to
      identify earlier stages of atherosclerosis.

PMID- 17007863
TI  - Simultaneous determination of binary diffusion coefficients from multiple
      response curves by chromatographic measurements.
AB  - The chromatographic impulse response technique with a polymer coated capillary
      column was applied to measurements of infinite dilution binary diffusion
      coefficients D and retention factors k in supercritical carbon dioxide by
      injecting a hexane solution dissolving a mixture of three unsaturated fatty acids
      such as alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid.
      The coefficients were simultaneously estimated by the curve fitting analysis even
      from partially overlapping response curves with the resolution of 0.8. The D and
      k values for each solute were able to be so obtained as accurately as those
      determined by individually injecting a single component solution. Almost no
      effect of the interaction among the components in the mixture was found from
      various approaching ways for curve fitting and the consecutive injection of the
      mixture at a certain interval.

PMID- 17007864
TI  - Qualitative and quantitative determination of ten major saponins in Platycodi
      Radix by high performance liquid chromatography with evaporative light scattering
      detection and mass spectrometry.
AB  - Saponins in Platycodi Radix (platycosides) exhibit potent biological activities
      in mammalian systems, including several beneficial effects such as anti
      inflammatory, immunomodulatory and anti-obesity activities. In this study, we
      developed a new HPLC separation coupled with evaporative light scattering
      detector (ELSD) for the simultaneous quantitative determination of ten major
      saponins in Platycodi Radix. Simultaneous separation of these saponins was
      achieved on a C18 analytical column. The mobile phase consisted of a gradient of
      aqueous acetonitrile. The method was validated for linearity, precision,
      accuracy, limit of detection and quantification. Electrospray ionization mass
      spectrometry (ESI-MS) and liquid chromatography coupled with on-line mass
      spectrometry (LC-ESI MS/MS) were applied to identify platycosides in the purified
      fractions and in the crude extract. Under ESI-MS/MS conditions, the fragmentation
      patterns of [M-H]- ions exclusively show signals corresponding to cleavage of the
      glycosidic bonds, thus allowing a rapid identification of saponins in the crude
      extract of Platycodi Radix. The validated HPLC method provides a new basis of
      overall assessment on quality of Platycodi Radix, and ESI-MS/MS and LC-ESI MS/MS
      approaches offers analytical tools for a rapid screening of platycosides in the
      crude extract.

PMID- 17007865
TI  - Fatty acids by high-performance liquid chromatography and evaporative light
      scattering detector.
AB  - A high-performance liquid chromatographic (HPLC) separation method with an
      evaporative light-scattering detector (ELSD) has been developed for the
      separation and quantitative analysis of fatty acid methyl esters (FAME) in three
      different oils. Reverse-phased C18 HPLC separation of 13 FAME is achieved using a
      methanol/water eluent mixture. The retention times (RT) reflect the elution
      behavior of these compounds on C18 reversed-phase HPLC. The proposed method is
      tested on: soybean oil (Glycine max L.) as reference sample, rice bran oil (Oryza
      sativa L.), pumpkin seed oil (Cucurbita pepo L.) and algal oil (Arthrospira
      platensis Nordst.).

PMID- 17007866
TI  - Study of cetyltrimethylammonium and cetylpyridinium adsorption on
      montmorillonite.
AB  - Adsorption of cetyltrimethylammonium (CTA) and cetylpyridinium (CP) onto Na-rich
      montmorillonite (MMT) was studied. For this purpose, the adsorption isotherms of
      CTA and CP, along with desorption curves of metal cations (Na+, K+, Ca2+, Mg2+),
      were obtained by means of capillary isotachophoresis and atomic absorption
      spectrometry. Infrared, X-ray diffraction pattern, specific surface area,
      porosity, and moisture adsorption measurements of montmorillonite revealed that
      CTA and CP were adsorbed in monolayer arrangements. CTA is assumed to be attached
      to the negatively charged MMT surface mainly by electrostatic forces. On the
      other hand, CP, adsorbed in higher amounts, can be additionally bound via other
      interactions of pyridinium rings, such as induced and pi-pi interactions. By the
      surfactant adsorption, the montmorillonite surface became hydrophobic and its
      micro- and mesopores were significantly diminished. Using scanning electron
      microscopy, aggregation of such organically modified MMT particles was observed.

PMID- 17007867
TI  - Catalytic properties of carboxylic acid functionalized-polymer microsphere
      stabilized gold metallic colloids.
AB  - Polymer-microsphere-stabilized gold metallic colloids have been prepared by a
      novel strategy of simple and convenient reduction of the metallic salt through
      the stabilization of the active carboxylic acid group on the gel and surface
      layer of the microsphere. The nature of the interaction between the carboxylic
      acid and Au nanoparticles was studied in detail by XPS. Preliminary results
      indicate that polymer-microsphere-stabilized gold colloids are active catalysts
      for the reduction of 4-nitrophenol to 4-aminophenol with sodium borohydride as
      reductant. The catalytic properties of the stabilized catalyst for recycling were
      also investigated.

PMID- 17007868
TI  - Talking about parts of a past experience: The impact of discussion style and
      event structure on memory for discussed and nondiscussed information.
AB  - This experiment examined the impact of selective postevent discussion of high-
      and low-elaborative styles on 5- and 6-year-olds' (N = 47) memory for discussed
      and nondiscussed aspects of a staged event ("Visiting the Pirate"). The event
      contained both logically and arbitrarily connected scenes. Discussion was spaced
      over 3 days, and memory was assessed 1 day later. Compared with a no-discussion
      condition, memory for discussed information was enhanced after high- but not low
      elaborative discussion for both logically and arbitrarily connected scenes. For
      arbitrarily connected scenes, memory for nondiscussed aspects was impaired
      relative to the no-discussion condition, with the degree of impairment being
      equal after high- and low-elaborative discussion. In contrast, for logically
      connected scenes, memory for nondiscussed information was not impaired after
      discussion of either style.

PMID- 17007869
TI  - Holistic face processing is mature at 4 years of age: evidence from the composite
      face effect.
AB  - Although it is acknowledged that adults integrate features into a representation
      of the whole face, there is still some disagreement about the onset and
      developmental course of holistic face processing. We tested adults and children
      from 4 to 6 years of age with the same paradigm measuring holistic face
      processing through an adaptation of the composite face effect [Young, A. W.,
      Hellawell, D., & Hay, D. C. (1987). Configurational information in face
      perception. Perception, 16, 747-759]. In Experiment 1, only 6-year-old children
      and adults tended to perceive the two identical top parts as different,
      suggesting that holistic face processing emerged at 6 years of age. However,
      Experiment 2 suggested that these results could be due to a response bias in
      children that was cancelled out by always presenting two faces in the same format
      on each trial. In this condition, all age groups present strong composite face
      effects, suggesting that holistic face processing is mature as early as after 4
      years of experience with faces.

PMID- 17007871
TI  - X-ray interference studies of crossbridge action in muscle contraction: evidence
      from quick releases.
AB  - We have used a high-resolution small angle X-ray scattering system, together with
      a high-performance CCD camera, on the BioCAT beamline at the APS synchrotron
      radiation facility at the Argonne National Laboratory, to study X-ray
      interference effects in the meridional reflections generated by the arrays of
      myosin crossbridges in contracting muscle. These give information about axial
      movements of the myosin heads during contraction with sub-nanometer resolution.
      Using whole intact muscle preparations (frog sartorius) we have been able to
      record the detailed behavior of M3 (the first order meridional reflection from
      the myosin crossbridges, at 14.56 nm) at each of a number of quick releases of
      increasing magnitude, on the same specimen, and at the same time make similar
      measurements on higher order myosin meridional reflections, particularly M6. The
      latter provides information about the dispersion of lever arm angles of the actin
      attached myosin heads. The observations show that in isometric contraction the
      lever arm angles are dispersed through +/- 20-25 degrees on either side of a mean
      orientation that is about 60 degrees away from their orientation at the end of
      the working stroke: and that they move towards that orientation in synchronized
      fashion, with constant dispersion, during quick releases. The relationship
      between the shift in the interference fringes (which measures the shift of the
      myosin heads scattering mass towards the center of the sarcomere, and the changes
      in the total intensity of the reflections, which measures the changes in the
      axial profile of the heads, is consistent with the tilting lever arm mechanism of
      muscle contraction. Significant fixed contributions to the meridional reflections
      come from unattached myosin heads and from backbone components of the myosin
      filaments, and the interaction of these with the contributions from actin
      attached myosin heads determines the behavior of these reflections.

PMID- 17007872
TI  - Structural basis for Rab11-mediated recruitment of FIP3 to recycling endosomes.
AB  - The Rab11 GTPase regulates recycling of internalized plasma membrane receptors
      and is essential for completion of cytokinesis. A family of Rab11 interacting
      proteins (FIPs) that conserve a C-terminal Rab-binding domain (RBD) selectively
      recognize the active form of Rab11. Normal completion of cytokinesis requires a
      complex between Rab11 and FIP3. Here, we report the crystal structure and
      mutational analysis of a heterotetrameric complex between constitutively active
      Rab11 and a FIP3 construct that includes the RBD. Two Rab11 molecules bind to
      dyad symmetric sites at the C terminus of FIP3, which forms a non-canonical
      coiled-coiled dimer with a flared C terminus and hook region. The RBD overlaps
      with the coiled coil and extends through the C-terminal hook. Although FIP3
      engages the switch and interswitch regions of Rab11, the mode of interaction
      differs significantly from that of other Rab-effector complexes. In particular,
      the switch II region undergoes a large structural rearrangement from an ordered
      but non-complementary active conformation to a remodeled conformation that
      facilitates the interaction with FIP3. Finally, we provide evidence that FIP3 can
      form homo-oligomers in cells, and that a critical determinant of Rab11 binding in
      vitro is necessary for FIP3 recruitment to recycling endosomes during
      cytokinesis.

PMID- 17007870
TI  - Thioredoxin and ventricular remodeling.
AB  - Increasing bodies of evidence indicate that reactive oxygen species (ROS)
      produced by mitochondria and other sources play an essential role in mediating
      ventricular remodeling after myocardial infarction and the development of heart
      failure. Antioxidants scavenge ROS, thereby maintaining the reduced environment
      of cells and inhibiting ventricular remodeling in the heart. Thioredoxin not only
      functions as a major antioxidant in the heart but also interacts with important
      signaling molecules and transcription factors, thereby modulating various
      cellular functions. The activity of thioredoxin is regulated by a variety of
      mechanisms, such as transcription, localization, protein-protein interaction, and
      post-translational modification. In this review, we will summarize the cardiac
      effects of thioredoxin and the mechanisms by which thioredoxin mediates
      inhibition of ventricular remodeling.

PMID- 17007873
TI  - Towards a comprehensive analysis of the protein phosphatase 1 interactome in
      Drosophila.
AB  - Protein phosphatase type 1 (PP1) is one of the major classes of serine/threonine
      protein phosphatases, and has been found in all eukaryotic cells examined to
      date. Metazoans from Drosophila to humans have multiple genes encoding catalytic
      subunits of PP1 (PP1c), which are involved in a wide range of biological
      processes. Different PP1c isoforms have pleiotropic and overlapping functions;
      this has complicated the analysis of their biological roles and the
      identification of specific in vivo substrates. PP1c isoforms are associated in
      vivo with regulatory subunits that target them to specific locations and modify
      their substrate specificity and activity. The PP1c-binding proteins are therefore
      the key to understanding the role of PP1 in particular biological processes. The
      existence of isoform specific PP1c-binding subunits may also help to explain the
      unique roles of different PP1c isoforms. Here we report the identification of 24
      genes encoding Drosophila PP1c-binding proteins in the yeast two-hybrid system.
      Sequence analysis identified a minimal interacting fragment and putative PP1c
      binding motif for each protein, delimiting the region involved in binding to
      PP1c. Further two-hybrid analysis showed that virtually all of the interactors
      were capable of binding all Drosophila PP1c isoforms. One of the novel
      interactors, CG1553, was examined further and shown to interact with multiple
      isoforms by co-immunoprecipitation from Drosophila extracts and functional
      interaction with PP1c isoforms in vivo. Bioinformatic analyses implicate the
      putative PP1c-associated subunits in a diverse array of intracellular processes.
      Our identification of a large number of PP1c-binding proteins with the potential
      for directing PP1c's specific functions in Drosophila represents a significant
      step towards a full understanding of the range of PP1 complexes and function in
      animals.

PMID- 17007874
TI  - Elucidation of human choline kinase crystal structures in complex with the
      products ADP or phosphocholine.
AB  - Choline kinase, responsible for the phosphorylation of choline to phosphocholine
      as the first step of the CDP-choline pathway for the biosynthesis of
      phosphatidylcholine, has been recognized as a new target for anticancer therapy.
      Crystal structures of human choline kinase in its apo, ADP and phosphocholine
      bound complexes, respectively, reveal the molecular details of the substrate
      binding sites. ATP binds in a cavity where residues from both the N and C
      terminal lobes contribute to form a cleft, while the choline-binding site
      constitutes a deep hydrophobic groove in the C-terminal domain with a rim
      composed of negatively charged residues. Upon binding of choline, the enzyme
      undergoes conformational changes independently affecting the N-terminal domain
      and the ATP-binding loop. From this structural analysis and comparison with other
      kinases, and from mutagenesis data on the homologous Caenorhabditis elegans
      choline kinase, a model of the ternary ADP.phosphocholine complex was built that
      reveals the molecular basis for the phosphoryl transfer activity of this enzyme.

PMID- 17007875
TI  - A free energy cascade with locks drives assembly and maturation of bacteriophage
      HK97 capsid.
AB  - We investigated the thermodynamic basis of HK97 assembly by scanning calorimetry
      and cryo-electron microscopy. This pathway involves self-assembly of hexamers and
      pentamers of the precursor capsid protein gp5 into procapsids; proteolysis of
      their N-terminal Delta-domains; expansion, a major conformational change; and
      covalent crosslinking. The thermal denaturation parameters convey the changes in
      stability at successive steps in assembly, and afford estimates of the
      corresponding changes in free energy. The procapsid represents a kinetically
      accessible local minimum of free energy. In maturation, it progresses to lower
      minima in a cascade punctuated by irreversible processes ("locks"), i.e.
      proteolysis and crosslinking, that lower kinetic barriers and prevent regression.
      We infer that Delta-domains not only guide assembly but also restrain the
      procapsid from premature expansion; their removal by proteolysis is conducive to
      initiating expansion and to its proceeding to completion. We also analyzed the
      mutant E219K, whose capsomers reassemble in vitro into procapsids with vacant
      vertices called "whiffleballs". E219K assemblies all have markedly reduced
      stability compared to wild-type gp5 (DeltaT(p) approximately -7 degrees C to -10
      degrees C; where T(p) is the denaturation temperature). As the mutated residue is
      buried in the core of gp5, we attribute the observed reduction in stability to
      steric and electrostatic perturbations of the packing of side-chains in the
      subunit interior. To explain the whiffleball phenotype, we suggest that these
      effects propagate to the capsomer periphery in such a way as to differentially
      affect the stability or solubility of dissociated pentamers, leaving only
      hexamers to reassemble.

PMID- 17007876
TI  - Conserved small non-coding RNAs that belong to the sigmaE regulon: role in down
      regulation of outer membrane proteins.
AB  - Enteric bacteria respond to misfolded proteins by activating the transcription of
      "heat shock" genes. These genes are arranged in two major regulons controlled by
      the alternative sigma factors sigmaH and sigmaE. The two transcription factors
      coordinate the stress response in different cellular compartments; the sigmaH
      regulon is induced by stress in the cytoplasm whereas the sigmaE regulon is
      activated by stress signals in the cell envelope. In Escherichia coli sigmaE
      plays a central role in maintaining cell envelope integrity both under stress
      conditions and during normal growth. Previous work established that sigmaE is
      essential for viability of the bacterium and up-regulates expression of
      approximately 100 protein-encoding genes that influences nearly every aspect of
      the cell envelope. Moreover, the expression of several outer membrane proteins is
      down-regulated upon sigmaE activation. Here, we show that two Hfq-binding small
      RNAs, MicA and RybB, are under positive control of sigmaE. Transient induction of
      RybB resulted in decreased levels of the mRNAs encoding OmpC and OmpW. sigmaE 
      mediated regulation of ompC and ompW expression was abolished in strains lacking
      RybB or Hfq. Recently MicA was shown to act in destabilizing the ompA transcript
      when rapidly grown cells entered the stationary phase of growth. Also, the
      alternative sigma factor down-regulates this message in a small non-coding RNA
      dependent fashion. These findings add the sigmaE regulon to the growing list of
      stress induced regulatory circuits that include small regulatory RNAs and provide
      insight in a homeostatic loop that prevent a build-up of unassembled outer
      membrane proteins in the envelope.

PMID- 17007877
TI  - Structural basis for nucleic acid and toxin recognition of the bacterial
      antitoxin CcdA.
AB  - Toxin-antitoxin systems are highly abundant in plasmids and bacterial
      chromosomes. They ensure plasmid maintenance by killing bacteria that have lost
      the plasmid. Their expression is autoregulated at the level of transcription.
      Here, we present the solution structure of CcdA, the antitoxin of the ccd system,
      as a free protein (16.7 kDa) and in complex with its cognate DNA (25.3 kDa). CcdA
      is composed of two distinct and independent domains: the N-terminal domain,
      responsible for DNA binding, which establishes a new family of the ribbon-helix
      helix fold and the C-terminal region, which is responsible for the interaction
      with the toxin CcdB. The C-terminal domain is intrinsically unstructured and
      forms a tight complex with the toxin. We show that CcdA specifically recognizes a
      6 bp palindromic DNA sequence within the operator-promoter (OP) region of the ccd
      operon and binds to DNA by insertion of the positively charged N-terminal beta
      sheet into the major groove. The binding of up to three CcdA dimers to a 33mer
      DNA of its operator-promoter region was studied by NMR spectroscopy, isothermal
      titration calorimetry and single point mutation. The highly flexible C-terminal
      region of free CcdA explains its susceptibility to proteolysis by the Lon ATP
      dependent protease.

PMID- 17007878
TI  - The solution structure of a domain from the Neisseria meningitidis lipoprotein
      PilP reveals a new beta-sandwich fold.
AB  - Type IV pili are long, thin fibres, which extend from the surface of the
      bacterial pathogen Neisseria meningitidis; they play a key role in adhesion and
      colonisation of host cells. PilP is a lipoprotein, suggested to be involved in
      the assembly and stabilization of an outer membrane protein, PilQ, which is
      required for pilus formation. Here we describe the expression of a recombinant
      fragment of PilP, spanning residues 20 to 181, and determination of the solution
      structure of a folded domain, spanning residues 85 to 163, by NMR. The N-terminal
      third of the protein, from residues 20 to 84, is apparently unfolded. Protease
      digestion yielded a 113 residue fragment that contained the folded domain. The
      domain adopts a simple beta-sandwich type fold, consisting of a three-stranded
      beta-sheet packed against a four-stranded beta-sheet. There is also a short
      segment of 3(10) helix at the N-terminal part of the folded domain. We were
      unable to identify any other proteins that are closely related in structure to
      the PilP domain, although the fold appears to be distantly related to the
      lipocalin family. Over 40 homologues of PilP have been identified in Gram
      negative bacteria and the majority of conserved residues lie within the folded
      domain. The fourth beta-strand and adjacent loop regions contain a high
      proportion of conserved residues, including three glycine residues, which seem to
      play a role in linking the two beta-sheets. The two beta-sheets pack together to
      form a crevice, lined with conserved hydrophobic residues: we suggest that this
      feature could act as a binding site for a small ligand. The results show that
      PilP and its homologues have a conserved, folded domain at the C-terminal end of
      the protein that may be involved in mediating binding to hydrophobic ligands.

PMID- 17007880
TI  - A pilot study on early versus delayed hypertonic saline dextran resuscitation in
      a porcine model of near-lethal liver injury: early hemodynamic response and short
      term survival.
AB  - BACKGROUND: We studied the effects of early versus delayed fluid resuscitation on
      hemodynamic response and short-term survival in a porcine model of severe hepatic
      injury associated with hemorrhagic shock. MATERIALS AND METHODS: Eighteen
      anesthetized swine were randomized after standardized liver injury into two
      groups: early resuscitation (ER, n = 9) and delayed resuscitation (DR, n = 9).
      The ER and DR groups were resuscitated with hypertonic saline dextran (HSD) 20
      min and 40 min after the injury, respectively. Mean arterial pressure (MAP),
      cardiac output (CO), and arterial blood gases were measured in addition to
      vascular blood flow rates in the aorta, hepatic artery and portal vein. The
      duration of follow-up was 100 min. RESULTS: MAP decreased from 112 +/- 4 to 23 +/
      2 mmHg (P < 0.05) during 20 min after the injury. Bolus infusion of HSD
      significantly elevated MAP, CO, and flow rates in the aorta, portal vein and
      common hepatic artery in both groups. Portal vein flow remained relatively high
      during the shock. Intra-abdominal bleeding (ER, 701 +/- 42 mL; DR 757 +/- 78 mL)
      and the mortality rate (ER 44%; DR 33%) did not differ between the groups 100 min
      after injury (P > 0.05). Aortic flow, portal vein flow, common hepatic artery
      flow, MAP, CO, PaO(2), PaCO(2), base deficit, pH, hemoglobin measurements, and
      the volume of blood shed into the intraperitoneal cavity did not affect survival
      in the Cox regression analysis. CONCLUSIONS: Early versus delayed fluid infusion
      with HSD resulted in a comparable hemodynamic response and survival 100 min after
      injury. No rebleeding was observed.

PMID- 17007879
TI  - Partially unfolded forms and non-two-state folding of a beta-sandwich: FHA domain
      from Arabidopsis receptor kinase-associated protein phosphatase.
AB  - FHA domains adopt a beta-sandwich fold with 11 strands. The first evidence of
      partially unfolded forms of a beta-sandwich is derived from native-state hydrogen
      exchange (NHX) of the forkhead-associated (FHA) domain from kinase-associated
      protein phosphatase from Arabidopsis. The folding kinetics of this FHA domain
      indicate that EX2 behavior prevails at pH 6.3. In the chevron plot, rollover in
      the folding arm and bends in the unfolding arm suggest folding intermediates. NHX
      of this FHA domain suggests a core of six most stable beta-strands and two loops,
      characterized by rare global unfolding events. Flanking this stable core are beta
      strands and recognition loops with less stability, termed subglobal motifs. These
      suggest partially unfolded forms (near-native intermediates) with two levels of
      stability. The spatial separation of the subglobal motifs on the flanks suggests
      possible parallelism in their folding as additional beta-strands align with the
      stable core of six strands. Intermediates may contribute to differences in
      stabilities and m-values suggested by NHX or kinetics relative to chemical
      denaturation. Residual structure in the unfolded regime is suggested by
      superprotection of beta-strand 6 and by GdmCl-dependence of adjustments in amide
      NMR spectra and residual optical signal. The global folding stability depends
      strongly on pH, with at least 3 kcal/mol more stability at pH 7.3 than at pH 6.3.
      This FHA domain is hypothesized to fold progressively with initial hydrophobic
      collapse of its stable six-stranded core followed by addition of less stable
      flanking beta-strands and ordering of recognition loops.

PMID- 17007881
TI  - Major hepatic trauma: warm ischemic tolerance of the liver after hemorrhagic
      shock.
AB  - BACKGROUND: The management of severe hepatic trauma frequently involves exposing
      the liver to varying periods of warm ischemia. The ischemic tolerance of the
      liver, in the setting of hemorrhagic shock (HS) and trauma, is presently unknown.
      We tested the hypothesis that warm ischemic tolerance of the porcine liver will
      be decreased following resuscitation from HS. MATERIALS AND METHODS: Twenty-three
      Yorkshire pigs were divided into three groups: 1) hepatic ischemia alone (HI, n =
      9); 2) hemorrhagic shock alone (HS, n = 3); and 3) hemorrhagic shock plus hepatic
      ischemia combined (HSHI, n = 11). Following reperfusion, a liver biopsy was
      obtained and serial blood chemistries were sampled. RESULTS: Post-operative day 7
      mortality was increased in the HSHI group (7/11) compared to the HI (0/9) group,
      P = 0.038. Notably, deaths did not result from acute liver failure, but rather
      from intra-operative hemodynamic collapse shortly following hepatic reperfusion.
      In addition, the HSHI group experienced significantly elevated lactic acid, serum
      creatinine and liver enzyme levels. Analysis of the liver biopsy samples is
      consistent with a more severe liver injury in the HSHI group. CONCLUSIONS: The
      warm ischemic tolerance of the liver following resuscitation from HS is
      significantly decreased in this porcine model compared to HS or HI alone.
      Mortality was associated with acute intra-operative hemodynamic collapse
      occurring shortly after hepatic reperfusion.

PMID- 17007882
TI  - Cytotoxic gene therapy for human breast cancer in vitro.
AB  - BACKGROUND: Transcription factor PDX-1 is expressed by human pancreatic and
      breast cancers. Although cytotoxicity of PDX-1-directed RIP-TK/GCV gene therapy
      to pancreatic cancer cells has been demonstrated, the efficacy of this treatment
      in breast cancer cells is unknown. The purpose of this study was to determine the
      expression of PDX-1 and its effect on RIP activation in two human breast cancer
      cell lines, AU565 and T47D. We also investigated the efficacy of RIP-TK/GCV gene
      therapy and examined whether exogenous PDX-1 to would enhance its cytotoxic
      effect. MATERIALS AND METHODS: RT-PCR was used to determine PDX-1 expression.
      Gene constructs RSVLacZ and RIPLacZ were used for transient transfection and LacZ
      expression was determined using reporter assays. T47D cells were also transfected
      with adenoviral vectors. Cells were transfected with RIP-TK and the suboptimal
      level of GCV was determined for each cell line. Following GCV treatment,
      cytotoxicity was measured using MTS assays. The effect of exogenous PDX-1 on LacZ
      expression and RIP-TK cytotoxicity was determined. RESULTS: PDX-1 mRNA was
      expressed in human breast cancer cells and activated the RIP. Exogenous PDX-1
      enhanced LacZ expression in AU565 cells but not in T47D cells. Adenoviral
      transfection was more efficient in T47D cells than non-viral transfection. RIP-TK
      treatment was cytotoxic to AU565 and T47D cells and this effect was enhanced by
      exogenous PDX-1 with both transfection methods. CONCLUSIONS: RIP-TK/GCV therapy
      is cytotoxic to human breast cancer cells and exogenous PDX-1 enhances
      cytotoxicity. In vivo studies are necessary to determine the tumor specificity
      and efficacy of this treatment.

PMID- 17007883
TI  - TNF-alpha induces Lnk expression through PI3K-dependent signaling pathway in
      human umbilical vein endothelial cells.
AB  - BACKGROUND: A better understanding of activation process of endothelial cells
      (ECs) might reveal new ways of controlling inflammation. Adaptor proteins play
      crucial roles in ECs activation. Lnk is a newly discovered adaptor protein that
      has been proposed as a negative regulator of cytokine signaling. While limited
      information is available about Lnk in human ECs. This study was conducted to
      investigate the effect of TNF-alpha on Lnk expression in ECs and to identify the
      signal transduction pathway that is associated with Lnk regulation. MATERIALS AND
      METHODS: Primary human umbilical vein endothelial cells (HUVECs) were cultured
      with designated doses of TNF-alpha and harvested at designated time points. Then
      Lnk mRNA and protein were detected using real-time polymerase chain reaction,
      immunoprecipitation and Western blot analysis, respectively. RESULTS: The data
      demonstrated that Lnk mRNA and protein expression are induced significantly (P <
      0.05) by TNF-alpha in a dose- and time-dependent manner. This inductive effect
      was abolished while phosphatidylinositol 3-kinase (PI3K) pathway was blocked by
      the PI3K inhibitor LY294002 and Wortmannin. CONCLUSION: These results suggest
      that TNF-alpha induces Lnk expression through PI3K-dependent signaling pathway in
      HUVEC. This may indicate a role for this new adaptor protein in the regulation of
      TNF-alpha-induced ECs activation.

PMID- 17007884
TI  - The role of neutrophils and oxygen free radicals in post-operative adhesions.
AB  - BACKGROUND: Postoperative intra-abdominal adhesion formation remains a major
      surgical problem. Surgery induces an inflammatory reaction, which is responsible
      for adhesion formation. Neutrophils and their oxygen-free radicals are key
      mediators in the early post-operative inflammatory response. The present study
      evaluates the effect of either blocking the influx of neutrophils or its products
      by scavenging oxygen-free radicals on adhesion formation. MATERIALS AND METHODS:
      Reproducible rat models were used to induce post-surgical intra-abdominal
      adhesions. In the first experiment anti-neutrophil serum (ANS) was used to
      prevent neutrophils from entering the peritoneal cavity after surgery. In a
      second experiment superoxide dismutase (SOD), catalase, and mannitol were tested,
      to scavenge the superoxide, hydrogen peroxide, and hydroxyl radicals,
      respectively. RESULTS: In positive control groups 69 to 76% of the area of
      interest contained adhesions. In all experimental groups, except for mannitol, a
      significant reduction in post-surgical adhesion formation could be achieved. ANS
      reduced adhesion formation by 38% (P < 0.001) and SOD/catalase by 42% (P < 0.01).
      Mannitol could not reduce adhesion formation. CONCLUSIONS: Intra-abdominal influx
      of neutrophils after surgical peritoneal trauma plays an important role in post
      operative adhesion formation. Preventing the intra-abdominal influx of
      neutrophils in the early post-operative inflammatory reaction can reduce adhesion
      formation, but an even more selective approach, by scavenging its products,
      proved as efficient.

PMID- 17007885
TI  - Technology-enhanced interactive surgical education.
AB  - BACKGROUND: Our goal was to create surgical resident centered, interactive
      teaching modules rich in basic science and clinical content directly pertinent to
      patient care and surgical techniques that would facilitate education in the 80-h
      work week environment. METHODS: A systematic evaluation of available
      instructional tools determined that a technology-enhanced approach can
      effectively and efficiently address the new requirements for resident learning.
      An extensive evaluation of available technology determined the technology best
      suited to teaching the adult surgical learner. RESULTS: An on-line, multimedia
      based surgical education environment using WebCT Vista (WebCT, Inc., Lynnfield,
      MA) and Macromedia Breeze (Adobe Systems, Inc., San Jose, CA) software packages
      was implemented. The concept was constructed on tenets of adult learning theory
      and based on the APDS curriculum and ACGME core competencies. WebCT Vista serves
      as virtual scaffolding, and Macromedia Breeze functions to deliver content rich
      multimedia audio and visual presentations. Core subdiscipline teaching modules
      were created, comprised of individual lecture packets developed by faculty.
      Components for testing pre/post module knowledge, feedback and evaluations are
      built-in. The online nature allows for 24-h access at locations that are
      convenient to the resident. CONCLUSIONS: Teaching modules enable maximal trainee
      and instructor flexibility, which translates into optimal adult learning and
      teaching. Lecture packets can be conveyed to all residents with unlimited
      availability in the virtual domain. Further refinement and continued
      implementation will help fill the void in direct didactic teaching left by
      mandated work hour restrictions, allowing for more efficient learning and
      teaching. There is great potential for broad application of the concept and
      technology to other training programs.

PMID- 17007886
TI  - A mathematical model of plants as ecosystem engineers.
AB  - Understanding the structure and dynamics of plant communities in water-limited
      systems often calls for the identification of ecosystem engineers--key species
      that modify the landscape, redistribute resources and facilitate the growth of
      other species. Shrubs are excellent examples; they self-organize to form patterns
      of mesic patches which provide habitats for herbaceous species. In this paper we
      present a mathematical model for studying ecosystem engineering by woody plant
      species in drylands. The model captures various feedbacks between biomass and
      water including water uptake by plants' roots and increased water infiltration at
      vegetation patches. Both the uptake and the infiltration feedbacks act as
      mechanisms for vegetation pattern formation, but have opposite effects on the
      water resource; the former depletes the soil-water content under a vegetation
      patch, whereas the latter acts to increase it. Varying the relative strength of
      the two feedbacks we find a trade-off between the engineering capacity of a plant
      species and its resilience to disturbances. We further identify two basic soil
      water distributions associated with engineering at the single patch level, hump
      shaped and ring-shaped, and discuss the niches they form for herbaceous species.
      Finally, we study how pattern transitions at the landscape level feedback to the
      single patch level by affecting engineering strength.

PMID- 17007887
TI  - Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated
      apoptosis in lung cancer cells.
AB  - Ganoderma lucidum is a well-known traditional Chinese medicinal herb containing
      many bioactive compounds. Ganoderic acid T (GA-T), which is a lanostane
      triterpenoid purified from methanol extract of G. lucidum mycelia, was found to
      exert cytotoxicity on various human carcinoma cell lines in a dose-dependent
      manner, while it was less toxic to normal human cell lines. Animal experiments in
      vivo also showed that GA-T suppressed the growth of human solid tumor in athymic
      mice. It markedly inhibited the proliferation of a highly metastatic lung cancer
      cell line (95-D) by apoptosis induction and cell cycle arrest at G(1) phase.
      Moreover, reduction of mitochondria membrane potential (Delta psi(m)) and release
      of cytochrome c were observed during the induced apoptosis. Our data further
      indicate that the expression of proteins p53 and Bax in 95-D cells was increased
      in a time-dependent manner, whereas the expression of Bcl-2 was not significantly
      changed; thus the ratio of Bcl-2/Bax was decreased. The results show that the
      apoptosis induction of GA-T was mediated by mitochondrial dysfunctions.
      Furthermore, stimulation of the activity of caspase-3 but not caspase-8 was
      observed during apoptosis. The experiments using inhibitors of caspases (Z-VAD
      FMK, Z-DEVD-FMK and Z-IETD-FMK) confirmed that caspase-3 was involved in the
      apoptosis. All our findings demonstrate that GA-T induced apoptosis of metastatic
      lung tumor cells through intrinsic pathway related to mitochondrial dysfunction
      and p53 expression, and it may be a potentially useful chemotherapeutic agent.

PMID- 17007888
TI  - Antivasoconstrictor effect of the neuroprotective agent dexrazoxane in rat aorta.
AB  - Dexrazoxane is used clinically to reduce the cardiotoxicity of anthracycline
      cancer chemotherapeutic agents, acting by an iron-chelating antioxidant
      mechanism. In a study designed to explore the possible mechanism of the recently
      described neuroprotective effect of the drug in cerebral ischemia, its influence
      on vascular reactivity was determined in rat aortic rings. Dexrazoxane was found
      to be devoid of direct contractile or relaxant activity and to have no influence
      on responses to acetylcholine or histamine (relaxation), or to angiotensin or
      serotonin (contraction). In contrast, it decreased contractions to
      norepinephrine, as evidenced by rightward displacement of the concentration
      response curves. The effect was prevented by the removal of the endothelium and
      by the alpha(2)-adrenoceptor antagonist yohimbine; it was partially antagonized
      by the endothelium-derived depolarizing factor inhibitor clotrimazole, but was
      not affected by L-NAME or indomethacin, inhibitors of endothelial nitric oxide
      and prostacyclin production. The anti-contractile effect did not occur in rings
      stimulated with the alpha(1)-adrenoceptor agonist phenylephrine. It was concluded
      that dexrazoxane opposes norepinephrine vascular contraction by enhancing
      endothelial alpha(2)-adrenoceptor-mediated release of relaxing factor(s). The
      drug could thus offset the deleterious vasoconstriction elicited by the increased
      circulating catecholamines present during cerebral ischemia, and by this
      mechanism produce neuroprotection.

PMID- 17007889
TI  - Selectivity of fatty acid ligands for PPARalpha which correlates both with
      binding to cis-element and DNA binding-independent transactivity in Caco-2 cells.
AB  - It is thought that peroxisome proliferator-activated receptor alpha (PPARalpha)
      is a major regulator for fatty acid metabolism. Long-chain fatty acids have been
      shown to induce expression of the genes related to fatty acid metabolism through
      PPARalpha. However, it is unclear whether the intensity of PPARalpha activation
      is different among various fatty acids. In this study, we compared various fatty
      acids in the capability of PPARalpha activation by differential protease
      sensitivity assay (DPSA), electrophoretic mobility shift assay and GAL4-PPAR
      chimera reporter assay in intestinal cell line, Caco-2. DPSA revealed that
      polyunsaturated fatty acids of 18 to 20 carbon groups with 3-5 double bonds
      strongly induced a PPARalpha conformational change. The ligand-induced changes in
      the sensitivity to protease corresponded to the enhancement of the binding of
      PPARalpha-RXRalpha heterodimer to the PPAR-response element (PPRE). The GAL4-PPAR
      chimera reporter assay revealed that the DNA binding-independent transactivity of
      PPARalpha was induced by various fatty acids with a wide spectrum of intensity
      which correlated with the conformational change of PPARalpha. These results
      suggest that PPARalpha has greater selectivity to certain types of
      polyunsaturated fatty acids, and that the ligand-induced conformational change of
      PPARalpha leads to parallel increases in both DNA binding to the PPAR-response
      element and the DNA binding-independent transactivity.

PMID- 17007890
TI  - Parasitism as a source of potential distortion in studies on endocrine disrupting
      chemicals in molluscs.
AB  - The effects of endocrine disrupting chemicals (EDC) on molluscs in both marine
      and freshwater polluted environments are a continuing area of concern resulting
      in many field and laboratory studies. However, molluscs are commonly infected
      with trematode parasites which, in order to obtain sufficient nutrients for their
      own development, naturally disrupt the functioning of the endocrine system of the
      host. The physiological effects of parasitisation on the reproduction and immune
      response of molluscs are summarised, using a number of examples, and the
      implications for EDC studies are discussed.

PMID- 17007891
TI  - An approach to the intercalibration of benthic ecological status assessment in
      the North Atlantic ecoregion, according to the European Water Framework
      Directive.
AB  - The European Water Framework Directive (WFD) establishes a framework for the
      protection and improvement of transitional and coastal waters; its final
      objective is to achieve at least 'good water status' for all waters, by 2015. The
      WFD requires Member States (MSs) to assess the Ecological Status (ES) of water
      bodies. This assessment will be based upon the status of the biological,
      hydromorphological and physico-chemical quality elements, by comparing data
      obtained from monitoring networks to reference (undisturbed) conditions, and then
      deriving an Ecological Quality Ratio (EQR). One of the biological quality
      elements to be considered is the benthic invertebrate component and some
      structural parameters (composition, diversity and disturbance-sensitive taxa)
      must be included in the ES assessment. Following these criteria, several
      approaches to benthic invertebrate assessment have been proposed by MSs. The WFD
      requires that these approaches are intercalibrated. This contribution describes
      the comparison of the different methodologies proposed by United Kingdom, Spain,
      Denmark and Norway. Results show a high consistency between the approaches, both
      with regard to determining the EQR and boundary settings for the ES.

PMID- 17007892
TI  - Paradox of estuarine quality: benthic indicators and indices, consensus or debate
      for the future.
AB  - The European Water Framework Directive will have instituted the concept of
      Ecological Quality Status (EQS) as a way to assess the biological quality of
      water masses. The EQS will be based mainly upon the composition of the different
      biological compartments in the ecosystem specially the benthos as compared to
      certain reference sites. Such management tools are already well established for
      freshwater (i.e. biotic indices), but not for coastal and estuarine (i.e.
      transitional) waters. In the framework of the Seine-Aval programme a workshop on
      benthic indicators was organized at Wimereux (France) in June 2005. The aim of
      this workshop and this paper is (1) to present the experiences of the Seine Aval
      researchers, and the French scientific approaches to benthic indicators, with
      those international experiences and approaches that have been published or are
      under development; and (2) to examine the existing benthic tools and their
      possible use in the characterization of the state of estuarine ecosystems. The
      debate during the workshop and the numerous recently published on the WFD are
      discussed in term of the implementation of the WFD in transitional water bodies
      using benthic indicators and indices. Some proposals for the future underline the
      needs to re-examine and adapt the different index thresholds, to take into
      account physical disturbances, to inventory the existing conditions vs reference
      conditions and to be as pragmatic as possible in using the WFD in transitional
      waters.

PMID- 17007893
TI  - Harmonization of international risk assessment protocol.
AB  - For over centuries developments in food production and new food safety management
      systems in most developed countries have been perceived by many to be efficient
      in the prevention of food-borne disease. Nevertheless a number of problems remain
      dominant, one of these being the high level of food-borne microbiological disease
      which seems, for some pathogens, to have increased over the last decades. The
      development of an interdisciplinary approach with direct interaction between
      surveillance and risk analysis systems is described as a potential basis for
      improved prevention of food-borne disease. Quantitative microbiological risk
      assessment is a relatively new scientific approach, able to link data from food
      within the entire food chain and the various data on human disease to provide a
      clear estimation of risk. Today food safety is one of the WHOs top eleven
      priorities; the Organization calls for more systematic and aggressive steps to be
      taken to reduce significantly the risk of microbiological food-borne diseases.
      Dealing with this challenge is one of the major challenges for the 21st century
      in regard to food safety, implying a significant re-direction of food
      microbiology efforts in many parts of the world.

PMID- 17007894
TI  - When "happy" means "sad": neuropsychological evidence for the right prefrontal
      cortex contribution to executive semantic processing.
AB  - The contribution of the left inferior prefrontal cortex in semantic processing
      has been widely investigated in the last decade. Converging evidence from
      functional imaging studies shows that this region is involved in the "executive"
      or "controlled" aspects of semantic processing. In this study, we report a single
      case study of a patient, PW, with damage to the right prefrontal and temporal
      cortices following stroke. PW showed a problem in executive control of semantic
      processing, where he could not easily override automatic but irrelevant semantic
      processing. This case, thus, shows the necessary role of the right inferior
      prefrontal cortex in executive semantic processing. Compared to tasks previously
      used in the literature, our tasks placed higher demands on executive semantic
      processing. We suggest that the right inferior prefrontal cortex is recruited
      when the demands on executive semantic processing are particularly high.

PMID- 17007895
TI  - Tobacco use among youth and adults in Mainland China: the China Seven Cities
      Study.
AB  - OBJECTIVE: The China Seven Cities Study (CSCS) monitors geographic and temporal
      trends in tobacco use among adolescents and adults in seven cities throughout
      Mainland China: Harbin, Shenyang, Wuhan, Chengdu, Kunming, Hangzhou, and Qingdao.
      This article presents the methodology and prevalence data from the baseline
      survey of the CSCS, conducted in 2002. METHODS: Stratified random samples of
      middle schools, high schools, and colleges were selected within each city.
      Students and their parents completed self-report surveys of their tobacco use.
      Data were obtained from 6138 middle school students, 5848 academic high school
      students, 2448 vocational high school students, 2556 college students, and 25 697
      parents. RESULTS: Smoking prevalence varied across age groups, school types,
      genders, and cities. Past-month smoking prevalence was 9% among middle school
      students, 8% among academic high school students, 26% among vocational high
      school students, 21% among college students, and 40% among parents. Smoking
      prevalence was higher among males than among females, with larger gender
      disparities among adults than among youth. Smoking also varied across cities,
      with higher smoking prevalence in southwestern cities and lower prevalence in
      coastal cities. Intraclass correlations of students within schools are presented
      to inform statistical power estimates for further research in China. CONCLUSIONS:
      These results provide a baseline for future longitudinal studies of smoking in
      these cities and identify demographic groups at risk for tobacco-related disease.
      Effective smoking prevention programmes for youth and smoking cessation
      programmes for adults are needed in China, especially in the lower-income
      southwestern cities and in vocational high schools throughout the country.

PMID- 17007896
TI  - Usual drinking patterns and non-fatal injury among patients seeking emergency
      care.
AB  - OBJECTIVES: To explore the association between drinking patterns, irrespective of
      whether alcohol was consumed in the event of the injury or not, and different
      injury variables; and to identify settings and situations in which risky drinkers
      have an increased likelihood of injury. STUDY DESIGN: The study population
      consisted of all patients aged 18-70 years registered for an injury according to
      ICD-10 at a Swedish emergency department during an 18-month period. After
      informed consent, the injury patients were screened for drinking habits by the
      AUDIT-C questionnaire. The gender, age and drinking pattern of injury patients
      were compared with the general population. METHODS: A total of 2782 patients aged
      18-70 years were registered for an injury during the study period. The number of
      drop-outs was 631. Drop-outs include those who did not consent to participate,
      were severely injured, too intoxicated or did not fill out the questionnaire
      satisfactory. Thus, 77.3% of the target group were included for further analysis
      (1944 drinkers and 207 abstainers). The patients were categorized into three
      drinking categories: abstainers, non-risky and risky drinkers. Risky drinkers
      were defined according to usual weekly consumption of 80g or more of alcohol for
      women and 110g or more for men and/or heavy episodic drinking (i.e. having six
      glasses or more one glass=12g alcohol), or both, on one occasion at least once a
      month, valid for both women and men. To estimate the relationship between
      drinking patterns and the injury variables (environment, cause of injury,
      activity and diagnosis), odds ratios (OR) were calculated by logistic regression.
      Multiple logistic regression was used in order to control for age and sex
      differences between the various drinking and injury categories. RESULTS: The
      proportion of risky drinkers was higher in the study population compared with the
      general population in the same area. When controlling for age and sex, risky
      drinkers (OR 6.4(adj) Confidence interval CI 1.9-21.2) and non-risky drinkers (OR
      .4.5(adj) CI 1.4-14.5) displayed an increased risk for injury compared with
      abstainers, in amusement locations, parks, by or on lakes or seas, especially
      while engaged in play, hobby or other leisure activities (risky drinkers: OR
      2.8(adj) CI 1.3-5.6; non-risky drinkers: OR 2.4(adj) CI 1.2-4.6). All differences
      between drinking patterns in external cause of injury disappeared when age and
      sex were considered. During rest, meals and attending to personal hygiene, the
      non-risky drinkers had a lower probability of injury compared with abstainers (OR
      0.3(adj) CI 0.1-0.8). Non-risky drinkers had a higher probability than abstainers
      of suffering luxation (dislocation) or distortion (OR 1.6(adj) CI 1.1-2.5). Nine
      per cent of the study population reported that they believed that their injury
      was related to intake of alcohol. Half of this group were non-risky drinkers (CI
      for the 13.7% difference was 9.7-17.6). CONCLUSIONS: Few significant associations
      between drinking pattern and injury remained when age and sex were controlled
      for.

PMID- 17007897
TI  - Relationships between biomarkers of exposure and toxicokinetics in Fischer 344
      rats and B6C3F1 mice administered single doses of acrylamide and glycidamide and
      multiple doses of acrylamide.
AB  - Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic,
      mutagenic to somatic and germ cells and carcinogenic in rodents. AA is also
      formed in many commonly consumed starchy foods during cooking. Our previous
      toxicokinetic investigations of AA and its important genotoxic metabolite,
      glycidamide (GA), in rodents showed that AA is highly bioavailable from oral
      routes of administration, is widely distributed to tissues and that the dietary
      route, in particular, favors metabolism to GA. Measurements of DNA adducts in
      many tissues supported the hypothesis that AA is carcinogenic in rodent bioassays
      through metabolism to GA. The current investigation describes the development and
      validation of methodology for measuring hemoglobin (Hb) adducts with AA and GA in
      the same rodents previously used for toxicokinetic and DNA adduct measurements.
      The goal was to investigate possible relationships between these circulating
      biomarkers of exposure and serum toxicokinetic parameters for AA and GA and
      tissue GA-DNA adducts in rodents from both single and repeated dosing with AA.
      Significant correlations were observed between GA-Hb and liver GA-DNA adducts for
      either single or multiple dosing regimens with AA. Using available GA-Hb adduct
      data, empirical and allometric relationships permitted estimation of liver DNA
      adducts in humans in the range of 0.06-0.3 adducts/10(8) nucleotides. This
      approach may prove useful in extrapolating human cancer risks from findings in
      rodent bioassays.

PMID- 17007898
TI  - The psychophysical law of speed estimation in Michotte's causal events.
AB  - Observers saw an event in which a computer-animated square moved up to and made
      contact with another, which after a short delay moved off, its motion appearing
      to be caused by launch by the first square. Observers chose whether the second
      (launched) square was faster in this causal event than when presented following a
      long delay (non-causal event). The speed of the second object in causal events
      was overestimated for a wide range of speeds of the first object (launcher), but
      accurately assessed in non-causal events. Experiments 2 and 3 showed that
      overestimation occurred also in other causal displays in which the trajectories
      were overlapping, successive, spatially separated or inverted but did not
      occurred with consecutive speeds that did not produce causal percepts. We also
      found that if the first object in a causal event was faster, then Weber's law
      holds and overestimation of the launched object speed was proportional to the
      speed of the launcher. In contrast, if the second object was faster,
      overestimation was constant, i.e. independent of the launcher. We propose that
      the particular speed integration of causal display results in overestimation and
      that the way overestimation depends on V1 phenomenally affects the attribution of
      the source of V2 motion: either in V1 (in launching) or in V2 (in triggering).

PMID- 17007899
TI  - Detection of multidimensional targets in visual search.
AB  - Search performance for targets defined along multiple dimensions was investigated
      with an accuracy visual search task. Initially, threshold was measured for
      targets that differed from homogeneous distractors along a single dimension
      (e.g., a reddish target among achromatic distractors, or a right-tilted target
      among vertically oriented distractors). Threshold was then measured for a
      multidimensional target (a redundant target) that differed from homogeneous
      distractors along two dimensions (e.g., a reddish AND right-tilted target among
      achromatic, vertically oriented distractors). Search performance for
      multidimensional target combinations of chromaticity and luminance, chromaticity
      and orientation, and chromaticity and spatial frequency was tested. Measurements
      were evaluated within several summation models, allowing for a test of the
      mechanisms mediating the detection of multidimensional targets in search.
      Measurements were generally consistent with probability summation suggesting the
      particular combinations of stimulus dimensions tested were coded along
      independent, noisy, neural mechanisms.

PMID- 17007900
TI  - The global processing deficit in amblyopia involves noise segregation.
AB  - Some studies have reported deficits in amblyopia for global form and motion
      integration, whereas other studies have shown global integration of form and
      motion information to be normal in amblyopia. Here, we attempt to resolve this
      discrepancy by showing that amblyopes only exhibit selective performance deficits
      on global tasks that contain noise as well as signal. We hypothesized that signal
      integration is normal, but noise segregation is not. We used comparable global
      orientation and motion direction discrimination tasks to measure integration
      performance in the presence of controlled amounts of pedestal noise (i.e.,
      elements whose orientations or directions were randomly selected). We modelled
      the performance using an equivalent noise model, which has the parameters of
      internal noise and number of samples. Our results show that amblyopic eyes can
      integrate form (i.e., orientation) and motion information (i.e., motion
      direction) similarly to normals when all the information is signal (i.e., no
      pedestal noise). However, introducing pedestal noise perturbs the performance of
      the amblyopic eyes significantly more than that of the normal eyes.

PMID- 17007901
TI  - Learning alters local face space geometry.
AB  - The effects of learning on the geometry of face space were investigated by
      measuring thresholds for discrimination and recognition of synthetic faces. This
      was based on a novel experimental technique that permitted measurement of
      psychometric functions for face recognition. Two major results were obtained.
      First, thresholds for face recognition were significantly better than thresholds
      for discrimination among novel faces. Second, rapid discrimination in the
      neighborhood of learned faces was better than discrimination near novel faces.
      Control experiments showed that this discrimination improvement occurred only
      with learned faces, and it could not be explained by generalized discrimination
      learning. Thus, face learning selectively alters or distorts face space in the
      vicinity of learned faces. This alteration may be due to an improvement in the
      signal/noise ratio as a result of face learning.

PMID- 17007902
TI  - Contributions of lateral inhibition to object substitution masking and attention.
AB  - Lateral inhibition, the inhibition of neurons by other neurons at the same level,
      exists at several levels of the visual system. Implications of lateral inhibition
      for sensory coding and perception have been investigated with a mathematical
      model that accounts for many properties of metacontrast masking and brief storage
      of sensory information. Here that model simulates object substitution masking,
      where a target and mask appear simultaneously but the mask disappears after a
      variable delay. The target becomes strongly masked if the mask offset is delayed
      after target offset, and target visibility does not recover with longer mask
      offset delays. Object substitution masking is most effective if attention is
      diverted by the presence of many simultaneous masks, only one of which surrounds
      a target. The lateral inhibitory model reproduces the effects of attention on
      object substitution masking by exploiting the longer latency of response to
      unattended stimuli. Decreasing the interval over which sensory codes are
      analyzed, reflecting the shorter latency of response to attended stimuli, weakens
      the masking in a way that reflects the psychophysical effects of attention.

PMID- 17007903
TI  - Luminescence of imidazo[1,2-a]pyrazin-3(7H)-one compounds.
AB  - In this review I will discuss chemical principles of the luminescence of
      imidazo[1,2-a]pyrazin-3(7H)-one compounds described to date. The review is
      composed of two main parts, the first dealing with the bioluminescence of
      coelenterate luciferin "coelenterazine" and Cypridina luciferin in marine
      organisms and the second with the chemiluminescence of these luciferins and their
      analogues. In the second section, possible applications of chemiluminescence and
      enhanced chemiluminescence in the area of bioassay are also discussed.

PMID- 17007904
TI  - A comparison of river water quality sampling methodologies under highly variable
      load conditions.
AB  - When river water quality fluctuates over relatively short periods of time with
      respect to the sampling frequency, the collection of grab samples may be
      inappropriate for characterising average water quality. This paper presents the
      results of a water quality monitoring study carried out on a stretch of the river
      Lambro (northern Italy) dominated by a periodically overloaded sewage treatment
      works (STW) located near its upstream end. Water quality was strongly influenced
      by a pronounced diurnal cycle in pollutant loads caused by the regular emission
      of untreated waste water during periods of high domestic flow (daytime). Two
      different sampling techniques were employed: grab sampling and 24-h composite
      sampling using automatic samplers. Samples were collected at the plant overflow
      and at several sites along the river and analysed for two common ingredients of
      household detergents, linear alkylbenzene sulphonate (LAS) and boron (B) and for
      routine water quality variables. The results obtained show that: (1) The diurnal
      variability of point-source-derived chemical concentrations in the river
      downstream of the undersized STW increased with increasing removal efficiency in
      sewage treatment. (2) The shape of the diurnal concentration signal remained
      relatively intact for a considerable distance downstream of the STW for several
      water quality variables, suggesting that hydrodynamic dispersion plays a
      relatively minor role in controlling concentration patterns in this river. (3) In
      stream degradation of LAS was consistent with first order kinetics with a rate
      constant of 0.05-0.06 h(-1). (4) Grab sampling is a relatively inefficient
      methodology for capturing mean concentrations for rivers subjected to highly
      variable loads, especially when it is restricted to office hours. The
      inefficiency of grab sampling is more marked for substances (e.g. LAS) which are
      effectively removed during sewage treatment than for substances which are not.
      (5) For LAS, diurnal variability in the concentration signal decreases with
      distance downstream, making grab sampling an increasingly reliable methodology
      for estimating mean concentrations. (6) 24-h composite sampling is an efficient
      way of eliminating the effect of diurnal variations in load strength.

PMID- 17007905
TI  - Enzyme and fungal treatments and a combination thereof reduce olive mill
      wastewater phytotoxicity on Zea mays L. seeds.
AB  - The phytotoxicity of olive-mill wastewater (OMW) has been suggested to be mainly
      due to its phenolic components. This study investigated the impact of three
      different low-cost dephenolization treatments on the wastewater phytotoxicity. To
      this aim, germinability of maize (Zea mays L.) seeds sown on a sandy-loamy soil
      which had been spread with different volumes (from 40 to 160m(3)ha(-1)) of either
      biologically-treated OMW or relative incubation control was determined.
      Biological treatments included either Panus tigrinus liquid cultures or
      incubation with commercial laccase (1UIml(-1)) or an innovative sequential
      combination of laccase and P. tigrinus cultures. All treatments markedly reduced
      phytotoxicity and promising results were obtained with commercial laccase. In
      fact, germinability and mean germination times in soil spread with laccase
      treated OMW, did not significantly differ from those observed in soil irrigated
      with tap water (control) up to OMW volumes of 120m(3)ha(-1). Although the highest
      phenol reduction (ca. 81%) was obtained by the sequential use of laccase and P.
      tigrinus, the feasibility of the enzyme treatment is undoubtedly more convincing
      under the technological point of view.

PMID- 17007906
TI  - Comparison of organochlorine compound concentrations in colostrum and mature
      milk.
AB  - Human breast milk represents the best choice for the nutrition of infants. It is
      often used for monitoring human exposures to environmental chemicals. Uniquely
      suited to meet human biological needs, breast milk composition, especially fat
      content, changes significantly with time from delivery. With the aim to compare
      the concentration of organochlorine compounds (OCs) in colostrum versus mature
      milk, we obtained samples of fourth-fifth day postpartum milk (colostrum) and day
      14 postpartum milk (mature milk) from 12 women enrolled in the project "Early
      Childhood Development and PCB Exposure in Slovakia". The concentrations of
      selected organochlorine pesticides and congeners of polychlorinated biphenyls
      (PCBs) were measured using gas chromatography with electron capture detection and
      reported on lipid adjusted basis. No significant differences were found between
      organochlorine levels in colostrum and those in mature milk samples. A very close
      correlation was found between the concentrations of organochlorine compounds in
      colostrum and mature milk (Spearman correlation coefficient r=0.94-0.98 for PCBs,
      and r=0.85-0.99 for organochlorine pesticides, p<0.001 for all compounds). The
      present study concludes that the use of colostrum samples provides a close
      estimate of the child's exposure to OCs in the early neonatal period and
      demonstrates that, despite the lower fat content, colostrum specimens are
      adequate to conduct OC analyses.

PMID- 17007907
TI  - Seasonal variations in decomposition processes in a valley-bottom riparian
      peatland.
AB  - A year-long field survey was carried out at a valley-bottom riparian peatland
      site in North Wales, UK from January 2002 to December 2002 to examine the
      seasonal variation of decomposition processes and dissolved organic carbon (DOC)
      concentrations. Peat temperature, physicochemistry, organic carbon pools, basal
      CO(2) respiration and extracellular enzyme activities (beta-glucosidase,
      phosphatase, sulphatase and phenol oxidase) were monitored monthly. The results
      of a principle component eigenanalysis of field data show that concentrations of
      basal CO(2) respiration, soil solution DOC and phenolics were positively
      correlated to soil temperature (P<0.01, F=12.25; P<0.001, F=59.8; P<0.001,
      F=141.27) with Q(10) responses of 2.29, 6.42 and 14.42, respectively.
      Extracellular enzyme activities, however, were more strongly associated with
      seasonal changes in ion concentrations and did not correspond significantly to
      temperature alone suggesting limitations attributable to a combination of
      continuous anaerobiosis and/or the suppressive compounds. Restraints on soil
      enzyme activities may limit the loss of CO(2) from the microbial community that
      is dependent on soil enzyme activities for nutrient availability. The seasonal
      effect of temperature on DOC may be explained by increased plant rhizodeposition
      and microbial activity. These results do not imply that the long-term increasing
      trend in DOC export is explainable by temperature increase but suggest that
      temperature may be a key factor regulating the seasonal variation in DOC
      concentrations. Thus, seasonal temperature effects on DOC may represent an
      important component of long-term models of DOC export.

PMID- 17007908
TI  - Triclosan in plasma and milk from Swedish nursing mothers and their exposure via
      personal care products.
AB  - The bactericide triclosan is commonly used in e.g. plastics, textiles and health
      care products. In vitro studies on rat and human biological systems indicate that
      triclosan might exert adverse effects in humans. Triclosan has previously been
      found in human plasma and milk, but neither the primary source of human exposure
      nor the efficiency of triclosan transfer to human milk is known. In this study,
      plasma and milk were sampled from 36 mothers and analyzed for triclosan.
      Scrutinization of the women's personal care products revealed that nine of the
      mothers used toothpaste, deodorant or soap containing triclosan. Triclosan and/or
      its metabolites were omnipresent in the analyzed plasma and milk. The
      concentrations were higher in both plasma and milk from the mothers who used
      personal care products containing triclosan than in the mothers who did not. This
      demonstrated that personal care products containing triclosan were the dominant,
      but not the only, source of systemic exposure to triclosan. The concentrations
      were significantly higher in plasma than in milk, indicating that infant exposure
      to triclosan via breast milk is much less than the dose in the mother.

PMID- 17007909
TI  - A vulnerability study of the low-income elderly in the context of high
      temperature and mortality in Seoul, Korea.
AB  - INTRODUCTION: We investigated the impact of environmental high temperature on
      mortality in Seoul, Korea, and the consequences of high temperature-induced
      mortality with a focus on the low-income elderly. METHODS: Changes in the risk of
      death by age and income were estimated by a 1 degrees C increase in temperature
      using a generalized additive model adjusting for non-temperature related factors:
      time trends, seasonality, and air pollution. The study covered the years of 2000,
      2001, and 2002. RESULTS: We found that income and age were potential factors in
      high-temperature-induced excess mortality. Evidences to support these results are
      as follows: first, regarding the effect of an economic factor in the association
      between mortality and high temperature, the study shows that the mortality rate
      of the low-income group is higher, by as much as 1.3- to 1.7-fold, than that of
      the general population. Second, taking age into consideration, the mortality of
      low-income elderly people is 1.5-fold higher than that of the whole low-income
      group. The combined effect of income and age on mortality is estimated as 2.3
      fold higher than that of the general population. But the results of the low
      income and elderly group were not statistically significant due to wide standard
      deviation. CONCLUSIONS: The relationship between high-temperature-induced excess
      mortality, income, and age suggests the need for a public health message, yet
      many results were not statistically significant: preventive and health care
      interventions need to be administered to the elderly and low-income group during
      periods of high temperature.

PMID- 17007910
TI  - A mouse model for human atherosclerosis: long-term histopathological study of
      lesion development in the aortic arch of apolipoprotein E-deficient (E0) mice.
AB  - Apolipoprotein E-deficient mice, since their introduction in the early 1990s,
      have proved to be a very popular model for studying spontaneous
      hypercholesterolemia and the subsequent development of atherosclerotic lesions.
      The pathogenesis of atherosclerotic lesions in these mice mimics that found in
      humans on a very short time-scale. Atherosclerotic lesion development is
      especially prominent in the aortic arch. We have followed the progressive
      histopathological development of atherosclerotic lesions in the aortic arch of
      apolipoprotein E-deficient mice aged from 6 weeks to 18 months in 1 microm epoxy
      resin sections stained with alkaline toluidine blue, which gives greatly improved
      resolution over wax sections. During the early stages of lesion formation, lipid
      filled macrophages appear in the subendothelium, and accumulate leading to "fatty
      streaks". Macrophage degeneration and the formation of lipid pools are
      accompanied by accumulation of cholesterol deposits. Disruptions of elastic
      laminae of the Tunica media are accompanied by structural changes in the
      myocytes. More advanced lesions involve fibrous cap development, calcification of
      the vessel wall and progressive occlusion of the lumen. Unstable plaque may also
      be found. Various approaches for quantitative determination of lesion size are
      considered. The study provides a histopathological baseline for spontaneous
      atherosclerosis associated with hypercholesterolemia, which can be used in
      connection with experimental interventional studies on the efficacy of drugs or
      foodstuffs in retardation of atherosclerosis.

PMID- 17007911
TI  - Alterations of seizure-induced c-fos immunolabelling and gene expression in the
      rat cerebral cortex following dexamethasone treatment.
AB  - We examined the effects of dexamethasone on the expression of the inducible
      transcription factor c-fos in 4-aminopyridine (4-AP) seizures. Induction of c-fos
      mRNA due to 4-AP-elicited convulsion was detected by means of the polymerase
      chain reaction (PCR) in samples from the neocortex. Adult male rats were
      pretreated with different doses of dexamethasone (0.5, 1, 3, 5mg/kg body weight);
      1h later 5mg/kg 4-AP was injected intraperitoneally. Controls received the
      solvent of dexamethasone. Pretreatment with dexamethasone provided significant
      symptomatic protection against 4-AP-induced convulsions. Immunohistochemistry was
      used to evaluate the presence of the c-fos protein. The number of Fos
      immunoreactive nuclei per section area was measured in the neocortex and
      hippocampus. Pretreatment with dexamethasone resulted in a dose-dependent,
      significant decrease of seizure-induced Fos-protein immunoreactivity in the
      neocortex, in the hilum of the dentate fascia, as well as in regions CA1-3 of the
      hippocampus, compared to control animals. Brains processed for mRNA isolation and
      PCR, displayed a significant increase of c-fos mRNA following the 4-AP treatment,
      while pretreatment with dexamethasone did not prevent or decrease this boosted c
      fos mRNA expression. We conclude that seizure-induced c-fos expression and
      intracellular Fos-protein localization are mediated by transmitter and receptor
      systems, and dexamethasone significantly decreases Fos immunoreactivity, probably
      by regulating the intracellular traffic of the protein. We also conclude that
      dexamethasone does not interfere with the genomic regulation of c-fos mRNA
      synthesis.

PMID- 17007912
TI  - Rapporteur report: Basics and technology and metrology and standards.
AB  - The first and second sessions of the Workshop focussed on the basics of
      ultrasound and infrasound, their applications in both industry and medicine, and
      metrology and protection standards for ultrasound applications.

PMID- 17007913
TI  - Retroperitoneal liposarcoma weighing over one hundred pounds with review of the
      literature.
AB  - BACKGROUND: Rarely, excessively large, slow growing tumors are found to be
      malignant. One exception includes retroperitoneal tumors, which if considered a
      mass of pelvic origin, may be encountered by the gynecologic oncologist. CASE: A
      post-menopausal female was referred for evaluation of a huge mass thought to
      arise from the pelvis. The patient underwent exploratory laparotomy and had
      resected a 50x48x45 cm, 103.6 lb. liposarcoma arising from the right
      retroperitoneum. DISCUSSION: Rarely, large slow growing abdomino-pelvic masses
      may be malignant, and one should be prepared to perform an appropriate surgical
      resection. This case represents removal of the largest retroperitoneal
      liposarcoma reported.

PMID- 17007914
TI  - Fertility sparing therapy in a patient with placental site trophoblastic tumor: a
      case report.
AB  - BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare form of
      gestational trophoblastic disease (GTD) that is generally resistant to
      conventional chemotherapeutic treatment. Patients with localized disease are
      usually managed with hysterectomy. CASE: A 29-year-old female presented with
      vaginal bleeding and an elevated serum human chorionic gonadotropin (HCG). After
      initial observation, the patient experienced continued vaginal bleeding and a
      persistently elevated HCG. Therefore, she underwent a dilation and curettage and
      final pathology revealed PSTT. Since the patient desired future fertility, the
      patient received combination chemotherapy with etoposide, methotrexate,
      actinomycin-D followed by etoposide and cisplatin (EMA-EP). The patient had a
      complete response to chemotherapy and subsequently delivered a term infant 2
      years after completion of therapy. CONCLUSION: PSTT is thought to be a
      chemoresistant disease and the preferred method of treatment is hysterectomy or
      local uterine resection. However, combination chemotherapy is a reasonable option
      in a properly counseled patient who strongly desires future fertility.

PMID- 17007915
TI  - The full bibliography of Ernst Ludwig Wynder.
AB  - The chronology of lifetime publications authored and/or co-authored by Dr. Ernst
      L. Wynder spans a rich assortment of topics relating to the etiology and
      prevention of chronic diseases. Dr. Wynder's interdisciplinary approach to
      research in cancer and heart disease embraces the disciplines of epidemiology,
      biology, pathology, chemistry, biochemistry, tobacco sciences, and nutrition as
      well as health behavior, and health education. His works reflect his attention to
      diverse subjects from methodology in scientific endeavors, to mechanisms in
      carcinogenesis, brain development, alternative medicine, principles of disease
      prevention, history of medicine, and societal issues, as well as philosophy, and
      religion. In 1972 Dr. Wynder created the journal Preventive Medicine as an
      international forum for the exchange of ideas that address the promotion of
      health and prevention of disease in our time. Many of his ideas were developed
      and nurtured in the symposia and workshops the Journal has published.

PMID- 17007916
TI  - Reproductive patterns and reproductive pathologies of stray bitches in the
      tropics.
AB  - The objectives of this study were to determine the annual reproductive pattern
      and to estimate the frequency of reproductive pathologies in female mongrel stray
      dogs under tropical conditions. The genital tracts of 300 mongrel bitches from a
      municipal dog pound were examined post-mortem from January to December 2003.
      Season of the year, age, size, and body condition score (BCS) were recorded for
      each dog. The year was divided into three seasons: warm-dry (March-June), warm
      humid (July-October), and fresh-humid (November-February). Distribution of estrus
      periods was not influenced by any of the factors studied (i.e. season, age, size,
      BCS). A significantly lower number of pregnancies were recorded during the warm
      dry season, probably as a consequence of embryo resorption. Underweight animals
      had a significantly lower percentage of pregnancies than bitches of ideal BCS.
      More ovulations per bitch occurred during the warm-humid season than during the
      other seasons of the year, probably due to climatic factors. Bitches of medium
      and large size had more ovulations than those of small size. Of the 300 bitches
      examined, 43.5% had one or more genital pathologies. The most frequent
      pathologies found in the ovary, uterus, and vagina were epoophoron cysts (6.7%),
      serosal inclusion cysts (5.0%), and transmissible venereal tumors (15.3%), but
      the capacity of the females to come into estrus or to become pregnant was not
      affected by these conditions. We concluded that stray domestic bitches in the
      tropics were not seasonal breeders, but their reproductive pattern was apparently
      modified by environmental factors such as temperature and probably photoperiod.
      Although several bitches in the present study had reproductive pathology, the
      most prevalent pathologies did not adversely reproductive capacity.

PMID- 17007917
TI  - A meta-analysis of the effects of Vitamin E supplementation on the incidence of
      retained foetal membranes in dairy cows.
AB  - A meta-analysis was performed to consolidate the results of studies which have
      evaluated the effects of Vitamin E supplementation during the dry period on the
      risk of retained foetal membranes (RFM) in the dairy cow. Twenty studies
      demonstrated a beneficial response to Vitamin E whilst 21 found no benefit and 3
      reported an increase in the incidence of RFM in treated cows. The odds ratios
      (OR) of the available studies exhibited significant heterogeneity, so
      multivariable logistic regression analysis was performed to enable the
      identification of factors associated with the response to Vitamin E
      supplementation. Our multivariable analysis included parity and Vitamin E
      supplementation (control/treated) in the model, because all other factors were co
      linear. Results indicated that Vitamin E supplementation led to a reduction in
      the incidence of RFM. A second multivariable analysis was undertaken on a subset
      of the data including only supplemented cows to determine the influence of
      supplementation factors on the risk of RFM. All factors were co-linear with each
      other, therefore, only type of Vitamin E supplementation was included in this
      analysis. The regression model demonstrated that administration of the synthetic
      Vitamin E alpha-tocopheryl acetate was associated with a lower risk of RFM than
      treatment with natural Vitamin E (alpha-tocopherol) (P=0.047, OR=0.49), whereas
      the difference between the synthetic Vitamin E alpha-tocopherol acetate and
      natural Vitamin E just failed to attain statistical significance (P=0.059,
      OR=0.53). Overall the analyses indicate that Vitamin E supplementation during the
      dry period is associated with a reduced risk of RFM, and that the synthetic forms
      of Vitamin E are more effective than the natural compound.

PMID- 17007918
TI  - Developmental competence of bovine oocytes is not related to apoptosis incidence
      in oocytes, cumulus cells and blastocysts.
AB  - The number of follicles undergoing atresia in an ovary is very high, and
      isolation of cumulus-oocyte complexes (COCs) from such atretic follicles may
      impair subsequent embryo development in vitro. Our aim was to study if stringent
      selection by morphological assessment of COCs can improve embryo development, and
      to evaluate whether oocyte diameter is related with apoptotic ratio in oocytes
      and blastocysts. COCs from slaughtered cattle were recovered by follicle
      aspiration and classified depending on oocyte diameter: (A) <110 microm; (B) 110
      120 microm; (C) >120 microm. COCs were matured, fertilized and cultured in vitro.
      Early and late stages of apoptosis were detected by Annexin-V and TUNEL staining,
      respectively, in denuded oocytes, COCs and blastocysts. Immature oocytes from
      Group A showed higher apoptotic ratio assessed by TUNEL assay, and the COCs
      corresponding to this group also showed a higher proportion of apoptotic cumulus
      cells. After maturation, no differences were present in the incidence of
      apoptosis among oocytes from different groups, but COCs corresponding to the
      largest diameter showed less apoptotic cumulus cells. In addition, the percentage
      of apoptotic oocytes decreased during in vitro maturation in all groups.
      Apoptotic cell ratio (ACR) in blastocysts was not related to oocyte diameter. In
      conclusion, oocyte selection and oocyte morphological evaluation prior to
      maturation was not sufficient to select non-atretic oocytes. When oocyte diameter
      was used as an additional selection the embryonic developmental potential
      increased together with oocyte diameter, but this improvement was not related to
      a lower incidence of apoptosis in the largest oocytes.

PMID- 17007919
TI  - Fatigue behavior of resin composites in aqueous environments.
AB  - OBJECTIVES: Interaction between mechanical and chemical fatigue of resin
      composites was investigated. METHODS: Fatigue fracture resistance of composites
      after (1) water immersion and under (2) dry and (3) aqueous conditions was
      analyzed using a fatigue crack propagation test. The characteristics of fatigue
      crack propagation were expressed as the correlation between the fatigue crack
      growth rate (da/dN) and stress intensity factor range (DeltaK) and by the fatigue
      crack growth threshold (DeltaKth). Following the fatigue test, a fractographic
      examination was performed by scanning electron microscopy. RESULTS: Contrary to
      common perception, fatigue crack propagation was retarded under aqueous
      conditions but accelerated after water immersion. In addition, fatigue cracks
      detoured around inorganic macro-fillers, but penetrated organic fillers.
      SIGNIFICANCE: It was concluded that the inverse effects of water on fatigue
      resistance of composites are dependent on the experimental conditions. Moreover,
      inorganic macro-fillers were shown to be functional in retarding fatigue cracks
      in composites.

PMID- 17007921
TI  - Plasma-sprayed carbon nanotube reinforced hydroxyapatite coatings and their
      interaction with human osteoblasts in vitro.
AB  - Carbon nanotubes (CNT) possess excellent mechanical properties to play the role
      as reinforcement for imparting strength and toughness to brittle hydroxyapatite
      (HA) bioceramic coating. However, lack of processing technique to uniformly
      distribute multiwalled CNTs in HA coating and limited studies and sparse
      knowledge evincing toxicity of CNTs has kept researchers in dispute for long. In
      the current work, we have addressed these issues by (i) successfully distributing
      multiwalled CNT reinforcement in HA coating using plasma spraying to improve the
      fracture toughness (by 56%) and enhance crystallinity (by 27%), and (ii)
      culturing human osteoblast hFOB 1.19 cells onto CNT reinforced HA coating to
      elicit its biocompatibility with living cells. Unrestricted growth of human
      osteoblast hFOB 1.19 cells has been observed near CNT regions claiming assistance
      by CNT surfaces to promote cell growth and proliferation.

PMID- 17007920
TI  - Volumetric interpretation of protein adsorption: competition from mixtures and
      the Vroman effect.
AB  - A Vroman-like exchange of different proteins adsorbing from a concentrated
      mixture to the same hydrophobic adsorbent surface is shown to arise naturally
      from the selective pressure imposed by a fixed interfacial-concentration capacity
      (w/v, mg/mL) for which protein molecules compete. A size (molecular weight, MW)
      discrimination results because fewer large proteins are required to accumulate an
      interfacial w/v concentration equal to smaller proteins. Hence, the surface
      region becomes dominated by smaller proteins on a number-or-mole basis through a
      purely physical process that is essentially unrelated to protein biochemistry.
      Under certain conditions, this size discrimination can be amplified by the
      natural variation in protein-adsorption avidity (quantified by partition
      coefficients P) because smaller proteins (MW<50 kDa) have been found to exhibit
      characteristically higher P than larger proteins (MW<50 kDa). The standard
      depletion method is implemented to measure protein-adsorption competition between
      two different test proteins (i and j) for the same hydrophobic octyl sepharose
      adsorbent particles. SDS-gel electrophoresis is used as a multiplexing,
      separation-and-quantification tool for this purpose. Identical results obtained
      using sequential and simultaneous competition of human immunoglobulin G (IgG,
      protein j) with human serum albumin (HSA, protein i) demonstrates that HSA was
      not irreversibly adsorbed to octyl sepharose over a broad range of competing
      solution concentrations. A clearly observed exchange of HSA for IgG or fibrinogen
      (Fib) shows that adsorption of different proteins (i competing with j) to the
      same hydrophobic surface is coupled whereas adsorption among identical proteins
      (i or j adsorbing from purified solution) is not coupled. Interpretive theory
      shows that this adsorption coupling is due to competition for the fixed surface
      capacity. Theory is extended to hypothetical ternary mixtures using a
      computational experiment that illustrates the profound impact size-discrimination
      has on adsorption from complex mixtures such as blood.

PMID- 17007922
TI  - The effect of polypyrrole with incorporated neurotrophin-3 on the promotion of
      neurite outgrowth from auditory neurons.
AB  - This research aims to improve the nerve-electrode interface of the cochlear
      implant using polymer technology to encourage neuron survival, elongation and
      adhesion to the electrodes. Polypyrrole (Ppy) doped with p-toluene sulphonate
      (pTS) is an electroactive polymer into which neurotrophin-3 (NT3) can be
      incorporated. Ppy/pTS+/-NT3 was synthesised over gold electrodes and used as a
      surface for auditory neuron explant culture. Neurite outgrowth from explants
      grown on Ppy/pTS was equivalent to tissue culture plastic but improved with the
      incorporation of NT3 (Ppy/pTS/NT3). Electrical stimulation of Ppy/pTS/NT3 with a
      biphasic current pulse, as used in cochlear implants, significantly improved
      neurite outgrowth from explants. Using (125)I-NT3, it was shown that low levels
      of NT3 passively diffused from Ppy/pTS/NT3 during normal incubation and that
      electrical stimulation enhanced the release of biologically active NT3 in
      quantities adequate for neuron survival. Furthermore, Ppy/pTS/NT3 and its
      constituents were not toxic to auditory neurons and the Ppy/pTS/NT3 coating on
      gold electrodes did not alter impedance. If applied to the cochlear implant,
      Ppy/pTS/NT3 will provide a biocompatible, low-impedance substrate for storage and
      release of NT3 to help protect auditory neurons from degradation after
      sensorineural hearing loss and encourage neurite outgrowth towards the
      electrodes.

PMID- 17007923
TI  - Biomimetic hydrogels for enhanced loading and extended release of ocular
      therapeutics.
AB  - We have applied the principles of biomimesis by incorporating a natural receptor
      based rational design strategy in the synthesis of novel recognitive soft contact
      lenses. We have demonstrated the potential of biomimetic carriers to load
      significant amounts of ocular medication such as H(1)-antihistamines, as well as
      to release a therapeutic dosage of drug in vitro in a controlled fashion for 5
      days, with an even further extension in the presence of protein. Gels of multiple
      complexation points with varying functionalities outperformed gels formed with
      less diverse functional monomers and showed superior loading with a six-fold
      difference over control gels and a three-fold difference over less biomimetic
      gels. Moreover, mechanical and optical properties of these hydrogels agreed with
      conventional lenses, and increased loading was reflected in a reduced propagation
      of polymer chains. This approach can be extended to a wider biological spectrum
      in the design of novel, controlled and modulated delivery devices to alleviate
      ocular disorders and provide an alternative to topical therapy.

PMID- 17007924
TI  - Longitudinal inhibition of PI3K/Akt/mTOR signaling by LY294002 and rapamycin
      induces growth arrest of adult T-cell leukemia cells.
AB  - This study found that phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target
      of rapamycin (mTOR) signaling was activated in human T-cell lymphotropic virus
      type I (HTLV-1)-infected leukemia cells. Rapamycin (1-100 nM, 48h), the inhibitor
      of mTOR and its analog RAD001 (1-100 nM, 48 h)-induced growth inhibition and
      G0/G1 cell cycle arrest of these cells in association with de-phosphorylation of
      p70S6K and 4E-BP-1, although IC50 was not achieved. Paradoxically, rapamycin
      stimulated phosphorylation of Akt at Ser473. Blockade of Akt signaling by the
      PI3K inhibitor LY294002 (1-20 microM, 48 h) also resulted in the growth
      inhibition and G0/G1 cell cycle arrest of HTLV-1-infected cells, with IC50
      ranging from 5 to 20muM, and it caused de-phosphorylation of p70S6K and 4E-BP-1.
      Of note, when rapamycin was combined with LY294002, rapamycin-induced
      phosphorylation of Akt was blocked, and the ability of rapamycin to induce growth
      arrest of HTLV-1-infected T-cells and suppress the p-p70S6K and p-4E-BP-1
      proteins was potentiated. Moreover, both LY294002 and rapamycin down-regulated
      the levels of c-Myc and cyclin D1 proteins in these cells, and their combination
      further decreased levels of these cell cycle-regulating proteins. Taken together,
      longitudinal inhibition of PI3K/Akt/mTOR signaling represents a promising
      treatment strategy for individuals with adult T-cell leukemia.

PMID- 17007925
TI  - Hairy cell leukaemia complicated by anti-MAG paraproteinemic demyelinating
      neuropathy: resolution of neurological syndrome after cladribrine treatment.
AB  - Hairy cell leukaemia (HCL) occasionally displays a monoclonal gammopathy, yet the
      association of HCL with paraproteinemic demyelinating neuropathy (PDN) has not
      been reported. We describe a HCL case complicated by PDN and high titers of
      monoclonal IgM against myelin associated glycoprotein (MAG). Heavy and light
      chains of the patient's anti-MAG monoclonal protein were consistent with those
      expressed by HCL cells. After treatment with cladribrine, remission of HCL
      strictly paralleled disappearance of the IgM monoclonal protein and of the serum
      anti-MAG activity, and led to PDN clinical and electrophysiological improvement.
      Purine analogs may represent a choice in IgM PDN associated with
      lymphoproliferative disorders.

PMID- 17007926
TI  - Scutellaria baicalensis, a herbal medicine: anti-proliferative and apoptotic
      activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines.
AB  - Scutellaria baicalensis (S.B.) is a widely used Chinese herbal medicine. We
      initially investigated its in vitro anti-tumor activities. S.B inhibited the
      growth of ALL, lymphoma and myeloma cell lines by inducing apoptosis and cell
      cycle arrest at clinically achievable concentrations. The anti-proliferative
      effect was associated with mitochondrial damage, modulation of the Bcl family of
      genes, increased level of the CDK inhibitor p27(KIP1) and decreased level of c
      myc oncogene. HPLC analysis of S.B. showed it contains 21% baicalin and further
      studies confirmed it was the major anti-cancer component of S.B. Thus,
      Scutellaria baicalensis should be tested in clinical trials for these
      hematopoietic malignancies.

PMID- 17007927
TI  - A survival study and prognostic factors analysis on acute promyelocytic leukemia
      at a single center.
AB  - This study was aimed to investigate the factors influencing long-term survival on
      patients with acute promyelocytic leukemia. Here, we present a single center
      retrospective study with long-term follow-up to explore the prognostic factors
      and a rationale of the using of ATRA, chemotherapy and As(2)O(3) in the treatment
      of newly diagnosed APL patients. In total, 222 patients, 184 achieved complete
      remission (CR) with the CR rate of 82.88% and 22 patients died during early
      induction therapy with the early-death-rate of 10%. Total 171 newly diagnosed APL
      patients entering CR were retrospectively analyzed from November 1989 to December
      2004,with a median follow-up of 36 months (6-185 months). Univariate and
      multivariate analysis of eight factors potentially influencing survival and
      prognosis were carried out with Log-Rank and Cox regression method, including
      sex, age, initial WBC count, the level of lactic dehydrogenase (LDH), first
      induction regimen, days from induction therapy to CR, post-remission therapy and
      the status of PML-RAR alpha fusion gene by reverse transcription-polymerase chain
      reaction (RT-PCR). The results showed that the estimated 5-year overall survival
      (OS) and relapse-free survival (RFS) were 80.9+/-4.0 and 71.0+/-4.0%,
      respectively. Univariate analyses showed that initial WBC count, first induction
      regimen, days from induction therapy to CR, post-remission therapy regimen and
      the status of PML-RAR alpha in remission were important prognostic factors for
      long-term survival. Multivariate study showed that only post-remission therapy
      regimen was associated with RFS and OS. It is concluded that the post-remission
      treatment combining ATRA, As(2)O(3) and chemotherapy would significantly improve
      the long-term survival of APL patients achieving CR(1).

PMID- 17007928
TI  - Characterization of cytosolic glutathione S-transferases in California Halibut
      (Paralichthys californicus).
AB  - Two cytosolic glutathione S-transferase (GST) classes were isolated and
      characterized from California halibut (Paralichthys californicus) liver.
      Nanospray liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to
      elucidate peptide sequences and the proteins were identified as theta and alpha
      by searching against the NCBI non-redundant database (nrDB). Catalytic activity
      of the cytosolic GSTs towards 1-chloro-2,4-dinitrobenzene (CDNB) was determined
      to be 0.23+/-0.003 U/mg cytosolic protein.

PMID- 17007929
TI  - Methylmercury genotoxicity: a novel effect in human cell lines of the central
      nervous system.
AB  - Methylmercury is an important source of environmental contamination and the
      central nervous system (CNS) is one of the main target organs. Methylmercury
      genotoxicity was already demonstrated in peripherical tissues but was never
      detected in the brain. Thus, the objective of this work was to verify its
      genotoxic effect using brain cell lines. Glioblastoma (U373) and neuroblastoma
      (B103) human cell lines were exposed to methylmercury (0-10 microM). By measuring
      cellular viability, concentrations inducing <20% of cellular death (P<0.05) were
      selected: 1 and 0.1 microM. To detect micronuclei, 200,000 cells were treated
      with methylmercury for 24 h, and then incubated with cytochalasin B (2 microg/ml)
      for 72 h (U373) or 48 h (B103). The binucleation index, frequency of
      micronucleated cells, micronucleation index, metaphasic index and index of
      nucleoplasmic bridges were determined. Statistical analysis showed indices and
      percentages significantly higher (P<0.05) in methylmercury-treated cells. Each
      cell line was shown to be differently sensitive to each biomarker of genotoxic
      damage, which seems to indicate the existence of different mechanisms of
      toxicity. This work demonstrates, for the first time, MeHg ability to provoke
      genotoxicity in cells of brain origin with relatively low levels of exposure.

PMID- 17007930
TI  - CD55 in rat male reproductive tissue: differential expression in testis and
      expression of a unique truncated isoform on spermatozoa.
AB  - CD55 is a key regulator of complement activation, expressed on most tissues and
      cells in man and other mammals. In the rat, alternative splicing in the gene
      encoding CD55 yields GPI-anchored (GPI-CD55) and transmembrane (TM-CD55) forms.
      Published Northern blot analysis indicated that while GPI-CD55 was broadly
      expressed, TM-CD55 was primarily expressed in the testis, although the precise
      site of expression was not identified. To clarify the distribution of CD55
      isoforms in rat reproductive tissues, we first performed immunohistochemistry and
      Western blot analysis with an anti-rat CD55 mAb that recognized all reported CD55
      isoforms, and a polyclonal immunoglobulin specific for TM-CD55. CD55 was absent
      in testis prior to puberty. Post-puberty, CD55 was expressed at high levels on
      all spermiogenic cells from step 6 spermatid onward, and on mature spermatozoa
      focussed on the acrosome, but was absent from support cells and early
      progenitors. Enzymatic digestion revealed that GPI-CD55 was predominant in testis
      and spermatozoa. Staining for TM-CD55 with specific immunoglobulin confirmed its
      absence from mature sperm and expression on spermatids only between steps 11 and
      14 of development. GPI-CD55 on spermatozoa was of lower molecular weight than
      that in testis and other tissues; sequencing from spermatozoal mRNA identified a
      unique isoform of GPI-CD55 missing short consensus repeat 4. The predominant
      acrosome expression and presence of a unique, truncated isoform of CD55 on
      spermatozoa provides further support for the hypothesis that the acrosome is a
      highly specialized region in which closely regulated complement activation may
      contribute to reproductive function.

PMID- 17007931
TI  - Selection of cholera toxin specific IgNAR single-domain antibodies from a naive
      shark library.
AB  - Shark immunoglobulin new antigen receptor (IgNAR, also referred to as NAR)
      variable domains (Vs) are single-domain antibody (sdAb) fragments containing only
      two hypervariable loop structures forming 3D topologies for a wide range of
      antigen recognition and binding. Their small size ( approximately 12kDa) and high
      solubility, thermostability and binding specificity make IgNARs an exceptional
      alternative source of engineered antibodies for sensor applications. Here, two
      new shark NAR V display libraries containing >10(7) unique clones from non
      immunized (naive) adult spiny dogfish (Squalus acanthias) and smooth dogfish
      (Mustelus canis) sharks were constructed. The most conserved consensus sequences
      derived from random clone sequence were compared with published nurse shark
      (Ginglymostoma cirratum) sequences. Cholera toxin (CT) was chosen for panning one
      of the naive display libraries due to its severe pathogenicity and commercial
      availability. Three very similar CT binders were selected and purified soluble
      monomeric anti-CT sdAbs were characterized using Luminex(100) and traditional
      ELISA assays. These novel anti-CT sdAbs selected from our newly constructed shark
      NAR V sdAb library specifically bound to soluble antigen, without cross reacting
      with other irrelevant antigens. They also showed superior heat stability,
      exhibiting slow loss of activity over the course of one hour at high temperature
      (95 degrees C), while conventional antibodies lost all activity in the first 5
      10min. The successful isolation of target specific sdAbs from one of our non
      biased NAR libraries, demonstrate their ability to provide binders against an
      unacquainted antigen of interest.

PMID- 17007932
TI  - Association of the pre-B cell receptor (BCR) expression level with the quality of
      pre-BII cell differentiation reveals hierarchical pre-BCR function.
AB  - The expression of a pre-B cell receptor (pre-BCR) is required for allelic
      exclusion and pre-BII cell differentiation. V(H)12 microH chains are unusual in
      that they form pre-BCRs and mediate allelic exclusion, but most cannot drive pre
      BII cell differentiation. To explain this paradox, we examined pre-BCR functions
      and pre-BII cell differentiation in mice expressing microH chain transgenes
      encoding a B cell-permissible V(H)12 microH chain (designated 10/G4(6-1)), and a
      non-permissible V(H)12 microH chain (designated 8/G0). Compared with 10/G4 pre
      BCRs, 8/G0 pre-BCRs are expressed at low levels on the cell surface. 8/G0 pre
      BCRs mediate allelic exclusion, but 8/G0 pre-BII cells are defective in
      proliferation and expression of survival factors Bcl-2, Bcl-X(L) and hemokinin 1
      (HK1). Increasing 8/G0 microH chain production restores HK1 transcription and
      improves proliferation of pre-BII cells as well as later stage B cell
      development. These data reveal a hierarchy of pre-BCR function that determines
      the development and plasticity of early B cells.

PMID- 17007933
TI  - Antibiotic treatment of community acquired pneumonia varies widely across
      Germany.
AB  - Community Acquired Pneumonia (CAP) is a frequent and potentially fatal infectious
      disease which, in the majority of cases, needs an antibiotic intervention.
      OBJECTIVES: Aim was to evaluate antibiotic treatment patterns regarding all types
      of mono- and combination-therapy throughout the local clinical centres (LCCs)
      represented in the German competence network CAPNETZ (=Community Acquired
      Pneumonia Network) and to identify clinical indicators for regional differences.
      METHODS: We analysed outpatients and inpatients recruited between March 2003 and
      April 2005. Patient and treatment details were registered online using
      standardised data entry forms. A logistic regression model was issued for the 4
      most frequently applied antibiotics, adjusting for potentially relevant
      confounders. RESULTS: The study sample consisted of 3221 patients at the age of
      18 to 102 years. Overall, aminopenicillins plus betalactamase inhibitor (20.4%),
      fluoroquinolone (17.0%), macrolides combined with cephalosporins third generation
      (10.6%) and cephalosporins third generation (8.9%) were most frequently
      prescribed. After control for potential confounders, significant treatment
      differences remained between study sites. Regional variability of antibiotic CAP
      treatment could not be attributed to a number of clinical or sociodemographic
      factors. CONCLUSIONS: The presented treatment variability ranges within given
      guidelines, but indicates the need for an ongoing implementation of evidence
      based guidelines in order to avoid potential negative clinical or economic
      consequences.

PMID- 17007934
TI  - Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue
      syndrome (CFS): indication for the involvement of gram-negative enterobacteria in
      the etiology of CFS and for the presence of an increased gut-intestinal
      permeability.
AB  - There is now evidence that chronic fatigue syndrome (CFS) is accompanied by
      immune disorders and by increased oxidative stress. The present study has been
      designed in order to examine the serum concentrations of IgA and IgM to LPS of
      gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa,
      Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri,
      and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal
      controls. We found that the prevalences and median values for serum IgA against
      the LPS of enterobacteria are significantly greater in patients with CFS than in
      normal volunteers and patients with partial CFS. Serum IgA levels were
      significantly correlated to the severity of illness, as measured by the
      FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension,
      fatigue, concentration difficulties, and failing memory. The results show that
      enterobacteria are involved in the etiology of CFS and that an increased gut
      intestinal permeability has caused an immune response to the LPS of gram-negative
      enterobacteria. It is suggested that all patients with CFS should be checked by
      means of the IgA panel used in the present study and accordingly should be
      treated for increased gut permeability.

PMID- 17007935
TI  - Carbon dioxide provocation of anxiety and respiratory response in bipolar
      disorder.
AB  - BACKGROUND: Frequent bipolar/panic comorbidity implies bipolar individuals may
      experience CO2-provoked anxiety and changes in respiratory patterns similar to
      those experienced by individuals with panic disorder. METHODS: 16 euthymic
      bipolar individuals breathed air and air combined with 5% CO2 for 15 min each.
      Respiratory and subjective anxiety measures were collected. RESULTS: On CO2
      subjects were more anxious and breathed more deeply and rapidly than with air;
      the degree of increase in anxiety attributable to CO2 was directly correlated
      with the degree of increase in minute ventilation. Five individuals were assessed
      as having a panic attack. Panic response to CO2 was predicted by the degree of
      anxiety experienced with air alone. CONCLUSIONS: Comparison with the results of
      similar panic studies shows bipolar disorder is associated with enhanced
      respiratory response to CO2. Hypersensitivity to CO2 among bipolar individuals
      suggests a possible pathological mechanism common to both bipolar and panic
      disorders. These preliminary data support the expanded application of CO2
      challenges in bipolar subjects.

PMID- 17007936
TI  - Abnormalities of auditory event-related potentials in students with high scores
      on the Schizotypal Personality Questionnaire.
AB  - Some auditory event-related potential (ERP) abnormalities characterize both
      patients with schizophrenia and subjects with schizotypal personality disorder.
      It was therefore hypothesized that subjects from the community with schizotypal
      traits might also present ERP abnormalities. In this study, we compared auditory
      ERP latencies and amplitudes in 13 subjects with high (H-SPQ) and 12 subjects
      with low (L-SPQ) scores on the Schizotypal Personality Questionnaire (SPQ),
      selected from 198 Tunisian students. Auditory ERPs were recorded at Fz, Cz, and
      Pz, with a standard oddball paradigm. Smaller P300 amplitudes and delayed P300
      latencies were found in H-SPQ compared with L-SPQ participants. Confirming
      previous reports, our results suggest that reduced P300 amplitudes and delayed
      P300 latencies may be considered as vulnerability markers of the schizophrenia
      spectrum in nonclinical subjects from the community.

PMID- 17007937
TI  - Interaction of negative olfactory stimulation and working memory in schizophrenia
      patients: development and evaluation of a behavioral neuroimaging task.
AB  - Negative affect plays a crucial role in the psychopathology of schizophrenia.
      Although it is known that negative emotion has a strong effect on cognitive
      performance, this interaction has mainly been studied in healthy volunteers.
      Hence, working memory was assessed in 24 schizophrenia patients and 24 matched
      comparison subjects with a 0-back/2-back continuous performance test.
      Simultaneously, negative emotion was induced by olfactory stimulation. Although
      subjective ratings confirmed that stimulation with a negative odor was associated
      with a significant increase in negative affect in patients and healthy
      volunteers, working memory performance was affected differentially in healthy
      volunteers and schizophrenia patients. Whilst a similar trend of a reduced
      behavioral performance during negative odor stimulation was observed in patients,
      only controls demonstrated a significantly higher response time and a reduced
      number of correct reactions during higher working memory demands (2-back).
      Patients, on the other hand, revealed an increase in false alarms during both
      conditions. The present data indicate a differential effect of negative mood
      induction on working memory performance in schizophrenia patients and healthy
      subjects.

PMID- 17007938
TI  - Cognitive retraining for organizational impairment in obsessive-compulsive
      disorder.
AB  - Individuals with obsessive-compulsive disorder (OCD) have difficulties in
      organizing information during encoding associated with subsequent memory
      impairments. This study was designed to investigate whether impairments in
      organization in individuals with OCD can be alleviated with cognitive training.
      Thirty-five OCD subjects and 36 controls copied and recalled the Rey-Osterrieth
      Complex Figure Test (RCFT) [Osterrieth, P.A., 1944. Le test de copie d'une figure
      complexe: Contribution a l'etude de la perception et de la memoire (The test of
      copying a complex figure: A contribution to the study of perception and memory).
      Archive de Psychologie 30, 286-350.] before being randomly assigned to a training
      or non-training condition. The training condition was designed to improve the
      ability to organize complex visuospatial information in a meaningful way. The
      intervention phase was followed by another copy and recall trial of the RCFT.
      Both OCD and control subjects who underwent training improved more in
      organization and memory than subjects who did not receive organizational
      training, providing evidence that the training procedure was effective. OCD
      subjects improved more in organizational during encoding than control subjects,
      irrespective of whether or not they had received training. This suggests that
      organization impairment in OCD affects primarily the ability to spontaneously
      utilize strategies when faced with complex, ambiguous information but that the
      ability to implement such strategies when provided with additional trials is
      preserved. These findings support a distinction in OCD between failure to utilize
      a strategy and incapacity to implement a strategy.

PMID- 17007939
TI  - Chromosomal fragile site expression in Turkish psychiatric patients.
AB  - Chromosomal aberrations associated with psychiatric disorders may suggest regions
      in which to focus a search for genes predisposing to psychosis by a linkage
      strategy. Identification of these may be especially important given the unknown
      pathophysiology and the probable genetic heterogeneity of psychiatric disorders.
      In this study, the frequencies of folate sensitive fragile sites (FS) were
      compared among psychiatric disorders (e.g., schizophrenia, bipolar disorder, and
      other psychosis) and normal individuals. The rate of FS expression in the
      patients was considerably higher than in the controls. Sites 1p22, 1q21, 1q32,
      2q31, 3p14, 3p25, 5q22, 5q31, 6p21, 6q21, 6q25, 7q22, 7q32, 8q22, 10q21, 11q23,
      12q24, 13q32, 14q24, 16q22, 17q21, Xp22 and Xq26 were expressed more frequently
      in the patients. Thirty possible relevant chromosomal sites were identified in
      schizophrenia: 1q21, 1q32, 2p13, 2q21, 3p14, 3p25, 3q21, 5q22, 5q31, 6p21, 6q25,
      6q26, 7q21, 7q22, 7q32, 8q22, 9q21, 10q21, 11q23, 12q24, 13q32, 14q24, 16q22,
      17q21, Xp22, Xq22, and Xq26. Possible relevant sites were also identified in
      bipolar disorder: sites 1p36, 1q21, 1q32, 3p14, 3p25, 5q31, 7q22, 7q32, 11q23,
      12q24, 13q32, 14q24, Xp22, and Xq26. Sites in the other psychosis group were:
      1p22, 1p32, 1p36, 1q21, 1q32, 2q31, 3p14, 3p25, 5q31, 6p21, 6q21, 6q25, 6q26,
      7q22, 7q32, 8q22, 10q21, 11q23, 12q13, 12q24, 13q32, 16q22, 16q24, 17q21 and
      Xq26. Among patient groups, there were significant differences in bands 1p32,
      2p13, 2q21, 2q31, 3p14, 3p25, 5q31, 6q21, 6q26, 7q22, 7q32, 9q21, 11qq23, 12q13,
      12q24, 16q24, and Xq22 between schizophrenic and bipolar patients. These regions
      were more frequently expressed in schizophrenic patients than in bipolar
      patients. The 1p22, 1p32, and 16q24 regions were significantly more frequently
      expressed in the other psychosis group than in the bipolar group. These
      interesting regions, which may harbor important genes for psychosis, have
      produced strong support for linkage in the majority of genome scan projects.

PMID- 17007940
TI  - A novel calpain inhibitor for the treatment of acute experimental autoimmune
      encephalomyelitis.
AB  - Aberrant activation of calpain plays a key role in the pathophysiology of several
      neurodegenerative disorders. Calpain is increasingly expressed in inflammatory
      cells in EAE and is significantly elevated in the white matter of patients with
      multiple sclerosis, thus calpain inhibition could be a target for therapeutic
      intervention. The experiments reported here employed a myelin oligodendrocyte
      glycoprotein-induced disease model in C57Bl/6 mice (EAE) and a novel calpain
      inhibitor, targeted to nervous tissue. CYLA was found to reduce clinical signs of
      EAE and prevent demyelination and inflammatory infiltration in a dose- and time
      dependent manner. Oral administration of the diacetal prodrug was equally
      effective.

PMID- 17007941
TI  - Nasal and paranasal sinus endoscopy, computed tomography and microbiology of
      upper airways and the correlations with genotype and severity of cystic fibrosis.
AB  - OBJECTIVE: Many studies have assessed clinical and functional aspects of lower
      airway affections in cystic fibrosis. Conversely, few studies have been performed
      to assess the clinical and functional affections of upper airways. The objective
      of the present study was to correlate the variables obtained by nasal and
      paranasal sinuses endoscopy, paranasal sinus laboratory and computed tomography
      (CT) scan findings, and to check the association with severity and genotype of
      cystic fibrosis patients. METHODS: Clinical and laboratory study of 50 patients
      with cystic fibrosis at a university center. All patients were submitted to CT
      scan, nasal and paranasal endoscopy and bacterioscopy of maxillary sinus, trachea
      and oropharynx secretion. Severity of cystic fibrosis was assessed by Shwachman
      score and the most frequent genetic mutations were identified. RESULTS: The
      prevalence of polyposis in the studied population was 36% and it was greater
      among homozygote for DeltaF 508. Shwachman score was correlated with age
      (p=0.003). The genotype was correlated with presence of nasal polyposis
      (p=0.006). There was no association between affections in CT scan and severity of
      cystic fibrosis (CF). Patients presented high prevalence of early colonization of
      Pseudomonas aeruginosa. CONCLUSIONS: Sinus disease in CF patients presents
      several clinical, endoscopic and tomographic affections. Although most of them
      are not correlated with severity and disease genotype, severity of CF is
      correlated with age and presence of polyposis is genotype-dependent.

PMID- 17007942
TI  - Ivermectin selection on beta-tubulin: evidence in Onchocerca volvulus and
      Haemonchus contortus.
AB  - Ivermectin resistance is common in trichostrongylid nematodes of livestock, such
      as Haemonchus contortus. This anthelmintic is the only drug approved for mass
      administration to control onchocerciasis caused by the nematode parasite,
      Onchocerca volvulus. In parts of West Africa up to 18 rounds of ivermectin
      treatment have been administered to communities and there are reports of poor
      parasitological responses to treatment. Understanding ivermectin resistance and
      ivermectin selection is an important step to reduce selection pressure for
      resistance, and to develop molecular markers which can be used to monitor the
      development of resistance and its spread. Here we report evidence that ivermectin
      selection changes the frequency of beta-tubulin alleles in both the sheep
      parasite, H. contortus, and the human parasite, O. volvulus. In O. volvulus we
      have been able to look at the frequency of beta-tubulin alleles in O. volvulus
      obtained before any ivermectin was used in humans in Africa, and following its
      widespread use. In H. contortus, we have been able to look at the frequency of
      beta-tubulin alleles in a strain which has not seen any anthelmintic selection
      and in an ivermectin selected strain derived from the unselected strain. We have
      found ivermectin selects on beta-tubulin in both of these nematode species. In
      the case of O. volvulus, we had previously reported that ivermectin selects for
      specific single nucleotide polymorphisms in the O. volvulus beta-tubulin gene.
      This polymorphism results in three amino acid changes in the H3 helix of beta
      tubulin, as well as deletions in an associated intron. We report a simple PCR
      assay to detect the amplicon length polymorphism, resulting from these intronic
      deletions, which can be used to monitor the frequency of the beta-tubulin allele
      selected for by ivermectin in O. volvulus.

PMID- 17007943
TI  - Influences along the path to maturity: regulation of cellular levels of RNA.
AB  - Initiation of RNA transcription may be a rate-limiting step in gene expression
      but it is only the first of many regulatory processes that impinge on nascent RNA
      along its path to maturity. Discontinuity between gene expression patterns within
      the nucleus and the cytoplasm suggests that multiple post-transcription
      regulatory points greatly influence the final RNA product, even to the extent of
      dramatically shifting the gene targets identified as a defined regulatory
      response.

PMID- 17007944
TI  - Peroxisome targeting signal 1: is it really a simple tripeptide?
AB  - Originally, the peroxisomal targeting signal 1 (PTS1) was defined as a tripeptide
      at the C-terminus of proteins prone to be imported into the peroxisomal matrix.
      The corresponding receptor PEX5 initiates the translocation of proteins by
      identifying potential substrates via their C-termini and trapping PTS1s through
      remodeling of its TPR domain. Thorough studies on the interaction between PEX5
      and PTS1 as well as sequence-analytic tools revealed the influence of amino acid
      residues further upstream of the ultimate tripeptide. Altogether, PTS1s should be
      defined as dodecamer sequences at the C-terminal ends of proteins. These
      sequences accommodate physical contacts with both the surface and the binding
      cavity of PEX5 and ensure accessibility of the extreme C-terminus. Knowledge
      based approaches in applied Bioinformatics provide reliable tools to accurately
      predict the peroxisomal location of proteins not yet determined experimentally.

PMID- 17007945
TI  - Generalised and conditional inactivation of Pex genes in mice.
AB  - During the past 10 years, several Pex genes have been knocked out in the mouse
      with the purpose to generate models to study the pathogenesis of peroxisome
      biogenesis disorders and/or to investigate the physiological importance of the
      Pex proteins. More recently, mice with selective inactivation of a Pex gene in
      particular cell types were created. The metabolic abnormalities in peroxisome
      deficient mice paralleled to a large extent those of Zellweger patients. Several
      but not all of the clinical and histological features reported in patients also
      occurred in peroxisome deficient mice as for example hypotonia, cortical and
      cerebellar malformations, endochondral ossification defects, hepatomegaly, liver
      fibrosis and ultrastructural abnormalities of mitochondria in hepatocytes.
      Although the molecular origins of the observed pathologies have not yet been
      resolved, several new insights on the importance of peroxisomes in different
      tissues have emerged.

PMID- 17007946
TI  - The psychophysiological determinants of fatigue.
AB  - Driver fatigue is a major risk for road accidents that can often result in injury
      and death. However, considerable debate still exists concerning factors
      associated with driver fatigue. Because of the complex nature of fatigue, this
      paper reports a study that investigated both physiological and psychological
      determinants of fatigue. Three fatigue outcome measures were used, including a
      physiological, psychological and a combined physiological and psychological
      measure. Fifty participants performed a driving simulator task till they showed
      symptoms of fatigue and were assessed before and after the task. Significant
      factors associated with physiological fatigue included higher levels of baseline
      delta activity and an extraverted personality. Factors related to the
      psychological fatigue outcome measure included sleepiness, low healthy lifestyle
      status, an extraverted personality and tension-prone personality, and negative
      mood states. The combined fatigue outcome measure was associated with factors
      such as a tension-prone and extraverted personality, low systolic blood pressure,
      and negative mood states. The findings emphasize the importance of assessing
      fatigue using a range of outcome measures in order to achieve a thorough
      understanding of what factors contribute to fatigue and highlight the need to
      develop fatigue countermeasures that employ a broad range of measures.

PMID- 17007947
TI  - Expression changes of cation chloride cotransporters in the rat spinal cord
      following intraplantar formalin.
AB  - Cation chloride cotransporters, K(+)-Cl(-) cotransporter 2 (KCC2) and Na(+)-K(+)
      Cl(-) cotransporter 1 (NKCC1) are reported to be expressed in the neurons in the
      spinal cord and regulate intracellular Cl(-) concentration. Evidence has been
      accumulating that the expression of cation chloride cotransporters changes in
      inflammatory or neuropathic pain, and such changes take a part in pathophysiology
      of the persistent pain states. However, it is largely unknown how these
      cotransporters contribute to hyperalgesia in the acute pain state. We, therefore,
      investigated expression changes of KCC2 and NKCC1 in the spinal dorsal horn of
      the rat after the intraplantar injection of formalin as an acute nociceptive
      stimulus. The rats showed two phases (phases 1 and 2) of increase in pain-related
      behavior in response to formalin. We found that expression of KCC2-like
      immunoreactivity (IR) was reduced in lamina I and II in the lumbar spinal cord on
      the stimulated side in phase 1, and then recovered gradually. In contrast, the
      number of NKCC1-like IR-positive cells was unchanged over the period examined.
      These results suggest that KCC2, rather than NKCC1, mainly contributes to
      modulating excitability of the dorsal spinal cord neurons in the initial stage of
      formalin-evoked hyperalgesia.

PMID- 17007948
TI  - Synaptic pattern of AMPA receptor subtypes upon direction-selective retinal
      ganglion cells.
AB  - In the search for anisotropies that might contribute to a directional preference
      of direction-selective (DS) retinal ganglion cells (RGCs), we studied the
      distributions of AMPA receptor subtypes GluR1, GluR2/3, and GluR4 upon the
      dendritic arbors of DS RGCs of the rabbit with antibody immunocytochemistry. DS
      RGCs were injected with Lucifer yellow and the cells were identified by their
      characteristic morphology. The double-labeled images of dendrites and receptors
      were visualized by confocal microscopy and were reconstructed from high
      resolution confocal images. We found no evidence of asymmetry in any of the AMPA
      receptor subunits examined upon the dendritic arbors of both On and Off layers of
      DS RGCs. The present results indicate that direction selectivity appears to lie
      in presynaptic pattern.

PMID- 17007949
TI  - Campylobacter spp. contamination of chicken carcasses during processing in
      relation to flock colonisation.
AB  - The presence and numbers of campylobacters on chicken carcasses from 26 slaughter
      groups, originating from 22 single-house flocks and processed in four UK plants,
      were studied in relation to the level of flock colonisation determined by
      examining the caecal contents of at least ten birds per group. The prevalence of
      campylobacters on carcasses from five campylobacter-negative flocks processed
      just after other negative flocks was low (</=30%). Campylobacters were isolated
      from 90 to 100% of carcasses from three flocks which were partly colonised, with
      5, 5 and 30% of caecal contents positive, and which were processed after fully
      colonised flocks. All carcasses from the remaining fully colonised flocks were
      contaminated with campylobacters, and they had significantly (P<0.001) higher
      numbers per carcass (average of 5.3 log(10) cfu; range: 1.3 to >8.0 log(10) cfu)
      than carcasses originating from low prevalence flocks (average of 2.3 log(10)
      cfu; range: <1.1 to 4.1 log(10) cfu). There was a reduction in the numbers of
      campylobacters on carcasses between plucking and chilling in eight of ten fully
      colonised flocks. In another eight flocks, a significant (P<0.001) decrease (0.8
      log(10) cfu) in the number of campylobacters on carcasses from just before to
      after chilling was detected. Campylobacter spp. could be isolated from aerosols,
      particles and droplets in considerable numbers in the hanging-on, defeathering
      and evisceration areas but not in the chillers. This was the case even when
      campylobacters were not isolated from the target flock. Campylobacters on
      carcasses from two partly colonised flocks were either the same subtype, as
      determined by speciation, Multi-Locus Sequence Typing (MLST) and flaA Restricted
      Fragment Length Polymorphism (RFLP) typing, as those in the fully colonised
      flocks processed previously, although not necessarily the most prevalent ones; or
      were the same subtypes as those found in the caeca of the flock itself. The
      prevalences of the different campylobacter subtypes found on carcasses from two
      fully colonised flocks did not closely reflect those found in the caeca. MLST
      combined with flaA RFLP provided a good method for ascertaining the relatedness
      of strains isolated from carcasses and caecal contents. This study showed that
      carcass contamination is related to the within-flock prevalence of campylobacter
      colonisation, but that contamination from previously processed flocks was also
      significant, especially on carcasses from low prevalence flocks. Forced dry air
      cooling of carcasses reduced contamination levels.

PMID- 17007950
TI  - Biological control of postharvest spoilage caused by Penicillium expansum and
      Botrytis cinerea in apple by using the bacterium Rahnella aquatilis.
AB  - The epiphytic bacterium Rahnella aquatilis, isolated from fruit and leaves of
      apples, was tested for antagonistic properties against Penicillium expansum and
      Botrytis cinerea on Red Delicious apple fruit. In "in vitro" assays, this
      bacterium inhibited completely the germination of P. expansum and B. cinerea
      spores, but it needed direct contact with the spores to do it. However the
      putative mechanism seemed be different for the two pathogens. The bacterium did
      not produce extracellular antibiotic substances and when the acute toxicity test
      was performed no mortality, toxicity symptoms or organ alterations of the test
      animals (Wistar rats) were observed. Assays of biological control of P. expansum
      and B. cinerea on apple fruit were carried out at different temperatures. At 15
      degrees C and 90% RH, the incidence of disease caused by P. expansum on apples
      stored for 20 days, was reduced by nearly 100% by R. aquatilis (10(6) cells/ml),
      while in the case of B. cinerea, the reduction of decay severity was nearly 64%
      but there was no reduction in the incidence of disease. At 4 degrees C and 90% RH
      the treatment with the bacterium significantly inhibited the development of B.
      cinerea on apples stored for 40 days and the incidence of disease was reduced by
      nearly 100%, while the incidence of disease caused by P. expansum at 4 degrees C
      was 60%. The results obtained show that R. aquatilis would be an interesting
      microorganism to be used as a biocontrol agent.

PMID- 17007951
TI  - Isolation and characterization of Shiga toxin-producing Escherichia coli O157:H7
      and non-O157 from beef carcasses at a slaughter plant in Mexico.
AB  - The contamination of beef carcasses with Shiga toxin-producing O157:H7 and non
      O157 Escherichia coli (STEC) obtained from a slaughter plant in Guadalajara,
      Mexico was investigated. A total of 258 beef carcasses were sampled during a 12
      month period. All samples were assayed for STEC by selective enrichment in
      modified tryptone soy broth supplemented with cefixime, cefsulodin and
      vancomycin, followed by plating on Sorbitol MacConkey Agar supplemented with
      cefixime and tellurite (CT-SMAC). Simultaneously, all samples were assayed by
      immunomagnetic separation (IMS) and plated on CT-SMAC and CHROMagar. The presence
      of the stx1, stx2, eaeA and hly933 genes, recognized as major virulence factors
      of STEC, was tested for O157:H7 and non-O157 E. coli isolates by multiplex
      polymerase chain reaction (PCR). STEC was detected in two (0.8%) samples. One of
      these STEC isolates corresponded to the serotype O157:H7 showing stx2, eaeA and
      hyl933 genes. The other isolate corresponded to non-O157 STEC and only had the
      stx1 gene. Thirteen carcasses (5%) were positive for nonmotile E. coli O157 and 7
      (2.7%) were positive for E. coli O157:H7. The presence of O157:H7 and non-O157
      STEC on beef carcasses in this slaughter plant in Guadalajara, Mexico, emphasizes
      the importance of implementing the Hazard Analysis and Critical Control Point
      (HACCP) system, as well as the need for implementing, evaluating, and validating
      antimicrobial interventions to reduce the presence of potential pathogenic
      microorganisms.

PMID- 17007952
TI  - The effect of reuterin on the lag time of single cells of Listeria innocua grown
      on a solid agar surface at different pH and NaCl concentrations.
AB  - The lag time of single cells of Listeria innocua grown on the surface of Brain
      Heart Infusion Agar was studied by microscopy and image analysis. An experimental
      set-up that enabled relocation of the cells on the agar surface was developed and
      used to collect data from 50 to 100 individual cells at a time. Reuterin was
      added at different concentrations (0-10 AU/ml) and it was observed that it
      increased both the lag time of the cells and its variance. Furthermore, for a
      large proportion of cells, reuterin completely prevented the cell division within
      the time of observation. Reuterin in combination with low pH inhibited the cell
      division even more efficiently. A similar effect was observed for the combination
      of reuterin and sodium chloride. Our experimental set-up provides a good model
      system for generating data on the lag time of single cells on solid surfaces,
      which can improve the predictions of microbial growth on solid food matrices.

PMID- 17007953
TI  - Polyketone polymer: a new support for direct enzyme immobilization.
AB  - Polyketone polymer -[-CO-CH(2)-CH(2)-](n)-, obtained by copolymerization of
      ethene and carbon monoxide, is utilized for immobilization of three different
      enzymes, one peroxidase from horseradish (HRP) and two amine oxidases, from
      bovine serum (BSAO) and lentil seedlings (LSAO). The easy immobilization
      procedure is carried out in diluted buffer, at pH 7.0 and 3 degrees C, gently
      mixing the proteins with the polymer. No bifunctional reagents and spacer arms
      are required for the immobilization, which occurs exclusively via a large number
      of hydrogen bonds between the carbonyl groups of the polymer and the -NH groups
      of the polypeptidic chain. Experiments demonstrate a high linking capacity of
      polymer for BSAO and an extraordinary strong linkage for LSAO. Moreover, activity
      measurements demonstrate that immobilized LSAO totally retains the catalytic
      characteristics of the free enzyme, where only a limited increase of K(M) value
      is observed. Finally, the HRP-activated polymer is successfully used as active
      packed bed of an enzymatic reactor for continuous flow conversion and flow
      injection analysis of hydrogen peroxide containing solutions.

PMID- 17007954
TI  - Kinetic model of 1,3-specific triacylglycerols alcoholysis catalyzed by lipases.
AB  - A new model of enzymatic 1,3-specific alcoholysis of triacylglycerols has been
      developed. The irreversibility of the acyl bounds cleavage in glycerides, a
      reversible monoglycerides isomerization and an irreversible enzyme deactivation
      have been assumed. The Ping Pong Bi Bi mechanism with competitive inhibition by
      alcohol has been applied to describe rates of acyl bonds cleavage. The enzymatic
      propanolysis and iso-propanolysis of triacetin and tricaprylin catalyzed by
      immobilized lipase B from Candida antarctica (Novozym 435) have been investigated
      to verify the model. Good agreement between experimental data and calculations
      has been obtained. It was shown that the rate of tricaprylin alcoholysis is
      higher than the triacetin alcoholysis and that the rate of iso-propanolysis
      reactions are higher than propanolysis. The irreversible enzyme deactivation
      affects the conversion of glycerides whereas the competitive alcohol inhibition
      may be neglected. Empirical correlations of rates for monoglycerides
      isomerization and enzyme deactivation have been proposed.

PMID- 17007955
TI  - Urinary PGDS levels are associated with vascular injury in type 2 diabetes
      patients.
AB  - BACKGROUND: The presence of metabolic syndrome has been shown to be predictors of
      cardiovascular morbidity and mortality in patients with type 2 diabetes. In a
      cross-sectional clinical study, we investigated the association of metabolic
      syndrome with asymptomatic lacunar strokes and cardiovascular disease (CVD) and
      we compared its significance with urinary protein markers. METHODS: We studied
      Japanese type 2 diabetes patients (n=233, men=124, women=109). The diagnosis of
      metabolic syndrome was made according to WHO and International Diabetes
      Federation (IDF) criteria. Cardiovascular events were recorded and asymptomatic
      lacunar lesions were evaluated with magnetic resonance imaging (MRI). We also
      measured urinary levels of albumin, type IV collagen, beta2-microglobulin
      (beta2MG), N-acetyl-beta-d-glucosaminidase (NAG) and lipocalin-type prostaglandin
      D synthase (PGDS). RESULTS: The prevalence of metabolic syndrome is 31.3% (IDF)
      and 52% (WHO) in 233 patients and microalbuminuria was present in 62 subjects
      (26.6%). Metabolic syndrome (WHO) significantly associated with asymptomatic
      lacunar lesions (p=0.035, OR=2.854, CI 1.075-7.579), while metabolic syndrome
      (IDF) or urinary markers failed to associate with presence of asymptomatic
      lacunar lesions. The presence of metabolic syndrome or microalbuminuria did not
      show significant association with CVD; however, the elevation of beta2MG, NAG and
      PGDS showed significant association with CVD. By a logistic regression analysis
      using urinary proteins as independent variables, the presence of higher PGDS
      excretion independently associated with history of CVD (p=0.025, OR=3.847, CI
      1.180-12.545). CONCLUSIONS: In type 2 diabetes patients, the elevation of urinary
      PGDS secretion closely associated with cardiovascular events and may be a
      supplemental or additional marker to the criteria of metabolic syndrome.

PMID- 17007956
TI  - Coping strategies in immigrant men and women with type 2 diabetes.
AB  - The aim of this study was to assess coping strategies of foreign-born men and
      women with type 2 diabetes in relation to demographic (sex, age, time in Sweden),
      medical, and socio-economic situation, and as compared with Swedish-born
      patients. Participants were foreign-born type 2 diabetic patients of European and
      non-European origin in primary health care in Stockholm County, comprising 41 men
      and 36 women aged 35-64 years, compared with Swedish-born type 2 diabetes
      patients, 121 men and 111 women. The General Coping Questionnaire, which measures
      five main orientations, dichotomised into "positive" and "negative" factors, i.e.
      10 coping strategies, was used in the assessment. Medical and socio-economic data
      were obtained from medical records and postal questionnaires. Foreign-born men
      showed an impact on 6 of 10 coping strategies, and foreign-born women on 2 of 10
      coping strategies, as compared to Swedish-born subjects. Longer time since
      migration and higher educational level were associated with lower scores for
      stressful coping strategies, while having financial problems and receiving a
      disability pension were associated with higher scores. In conclusion, the most
      stressful coping strategies were found among foreign-born men. It seems to be
      essential to improve and adjust diabetes care for immigrants, also including the
      psycho-social perspective.

PMID- 17007957
TI  - Association between insulin resistance and endothelial dysfunction in type 2
      diabetes and the effects of pioglitazone.
AB  - Endothelial dysfunction is regarded as an early stage of atherosclerosis, and
      plays a role in the development of atherosclerotic diseases. Insulin resistance
      is related to the atherosclerotic process. In this study, we examined the
      association between endothelial function and insulin resistance in 48 subjects
      with type 2 diabetes. In addition, the effects of pioglitazone treatment on
      endothelial function and insulin resistance were investigated in a subgroup of
      subjects. Endothelial function of the brachial artery was non-invasively assessed
      using ultrasound technique. We measured flow-mediated endothelium-dependent
      vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent
      vasodilation (GTN). Insulin sensitivity was measured by the steady-state plasma
      glucose (SSPG) method. High SSPG levels indicate insulin resistance. There was a
      significant inverse correlation (r=-0.462, p<0.001) between SSPG and FMD.
      Systolic blood pressure was inversely correlated with FMD (r=-0.360, p<0.013). By
      multiple regression analysis, insulin resistance was the sole predictor of FMD.
      The effects of chronic treatment with pioglitazone were assessed in 10 subjects
      with type 2 diabetes. The increase in FMD significantly correlated with the
      decrease in SSPG. There is a significant association between vascular endothelial
      dysfunction and insulin resistance in type 2 diabetes. This result was supported
      by the effects of the insulin sensitizer, pioglitazone.

PMID- 17007958
TI  - Know thy mouse.
AB  - In science it is imperative that the basic reagents and materials are defined and
      uniform. Unlike chemical reagents, which are uniform over time, mice, like all
      living creatures, have an intrinsic genetic drive to change, with mutations
      accumulating over time leading to increasing genetic variation and phenotypic
      change. Such changes compromise the reproducibility of experimental data over
      time and place. The use of the mouse has expanded rapidly in recent years and
      many scientists who have turned to the mouse as a research model might be unaware
      of the profound impact of changes in genetic background. Here we discuss the
      sources of genetic change and strategies to reduce them with the idea of
      strengthening international genetic standards for inbred mice.

PMID- 17007959
TI  - Human cancer vaccines.

PMID- 17007960
TI  - Anaerobic dechlorination and redox activities after full-scale Electrical
      Resistance Heating (ERH) of a TCE-contaminated aquifer.
AB  - The effects of Electrical Resistance Heating (ERH) on dechlorination of TCE and
      redox conditions were investigated in this study. Aquifer and groundwater samples
      were collected prior to and after ERH treatment, where sediments were heated to
      approximately 100 degrees C. Sediment samples were collected from three locations
      and examined in microcosms for 250 to 400 days of incubation. Redox activities,
      in terms of consumed electron acceptors, were low in unamended microcosms with
      field-heated sediments, although they increased upon lactate-amendment. TCE was
      not dechlorinated or stalled at cDCE with field-heated sediments, which was
      similar or lower compared to the degree of dechlorination in unheated microcosms.
      However, in microcosms which were bioaugmented with a mixed anaerobic
      dechlorinating culture (KB-1) and lactate, dechlorination past cDCE to ethene was
      observed in field-heated sediments. Dechlorination and redox activities in
      microcosms with field-heated sediments were furthermore compared with controlled
      laboratory-heated microcosms, which were heated to 100 degrees C for 10 days and
      then slowly cooled to 10 degrees C. In laboratory-heated microcosms, TCE was not
      dechlorinated and redox activities remained low in unamended and lactate-amended
      sediments, although organic carbon was released to the aqueous phase. In
      contrast, in field-heated sediments, high aqueous concentrations of organic
      carbon were not observed in unamended microcosms, and TCE was dechlorinated to
      cDCE upon lactate amendment. This suggests that dechlorinating microorganisms
      survived the ERH or that groundwater flow through field-heated sediments carried
      microorganisms into the treated area and transported dissolved organic carbon
      downstream.

PMID- 17007962
TI  - Oscillations of the internal CO(2) concentration in tobacco leaves transferred to
      low CO(2).
AB  - Measurement of the internal CO(2) concentration (Ci) in tobacco leaves using a
      fast-response CO(2) exchange system showed that in the light, switching from 350
      microLL(-1) to a low CO(2) concentration of 36.5 microLL(-1) (promoting high
      photorespiration) resulted in the Ci oscillating near the value of CO(2)
      compensation point (Gamma*). The oscillations are highly irregular, the range of
      Ci varying by 2-4 microLL(-1) in substomatal cavities with a period of a few
      seconds. The statistical properties of the time series became stationary after a
      transient of approximately 100s following transfer to low CO(2). Attractor
      reconstruction shows that the observed oscillations are not chaotic but exhibit
      stochastic behavior. The period of oscillations is consistent with the duration
      of photorespiratory post-illumination burst (PIB). We suggest that the observed
      oscillations may be due to a similar mechanism to that which leads to PIB, and
      may play a role in switching mitochondrial operation between oxidation of the
      photorespiratory glycine and of the tricarboxylic acid cycle substrates.

PMID- 17007961
TI  - NtGRAS1, a novel stress-induced member of the GRAS family in tobacco, localizes
      to the nucleus.
AB  - We report the isolation and initial characterization of a new member of the GRAS
      gene family from tobacco, NtGRAS1. Analysis of the predicted amino acid sequence
      shows that NtGRAS1 shares the highly conserved carboxy-terminal motifs common to
      all members of the GRAS family. NtGRAS1 expression was strongly induced in
      tobacco (BY-2) suspension cells by antimycin A, H(2)O(2), salicylic acid, and L
      cysteine which were all found to raise intracellular reactive oxygen levels. An
      increase in NtGRAS1 expression was also triggered by treating cells with the
      nitric oxide donor sodium nitroprusside. By employing inhibitors of protein
      kinase and phosphatase action, we show that reversible phosphorylation is
      required for the stress-induced induction of NtGRAS1 and that reactive oxygen as
      well as NO-dependent signaling pathways probably share key intracellular
      components. Interestingly, in soil-grown plants, high constitutive expression of
      NtGRAS1 was found only in roots while expression was strongly induced in leaf
      tissue upon antimycin A treatment or following Pseudomonas syringae infection.
      Many members of the GRAS family are implicated in regulating transcription and
      this function for NtGRAS1 is supported by our finding that an NtGRAS1-GFP fusion
      protein localizes to the nucleus of onion epidermal cells. Our data suggest that
      NtGRAS1 may represent an important transcriptional regulator involved in the
      plant stress response.

PMID- 17007963
TI  - Genotype-related changes of ganglioside composition in brain regions of
      transgenic mouse models of Alzheimer's disease.
AB  - In this study, brain gangliosides of different transgenic mouse models of
      Alzheimer's disease (AD) were analyzed and compared with age-matched wild-type
      mice. Gangliosides were analyzed in cerebral cortex, a region with extensive A
      beta plaques, and cerebellum, a non-vulnerable region with no A beta containing
      plaques. There was a marked increase in simple gangliosides GM2 and GM3 only
      within the cortex of all mice expressing APP(SL). Additionally, loss of complex
      "a" gangliosides (GT1a, GD1a and GM1) was recorded in APP/PS1Ki model, whereas in
      APP(SL) and APP/PS1 mice, the complex "b" gangliosides (GQ1b, GT1b and GD1b)
      moderately decreased. Surprisingly, expression of either mutant PS1(M146L) or PS1
      mutant FAD (Ki model) alone tended to lower the levels of both GM2 and GM3 within
      the cortex. Conversely, only slight changes of the ganglioside pattern were found
      in the cerebellum. Because ganglioside alterations occurring in APP transgenic
      mice were similar to those observed in human AD brain, these transgenic models
      would represent valuable tools to further investigate the role of altered
      ganglioside metabolism in the pathogenesis of AD.

PMID- 17007964
TI  - Synthesis and antimicrobial studies on novel chloro-fluorine containing hydroxy
      pyrazolines.
AB  - A series of chloro-fluorine containing chalcones (3) were prepared by Claisen
      Schmidt condensation. Chalcone dibromides (4) were obtained by the bromination of
      chalcones at room temperature. Treatment of chalcone dibromides (4) with aryloxy
      acid hydrazides (5) in the presence of triethylamine gave chloro-fluorine
      containing hydroxy pyrazolines (7) rather than the expected 1-aryloxy-3-aryl-5
      aryl pyrazoles (6). The structures of the newly synthesized compounds were
      confirmed by IR, NMR, mass and elemental analysis. All the compounds were tested
      for their antibacterial and antifungal activities. Some compounds showed very
      good antibacterial activity and antifungal activity.

PMID- 17007965
TI  - Study on the substituents' effects of a series of synthetic chalcones against the
      yeast Candida albicans.
AB  - A large series of chalcones were synthesized and studied for activity against
      Candida albicans. The SAR analysis showed that the antifungal activity was highly
      dependent on the substitution pattern of the aryl rings and correlated to a large
      extent with the ability of compounds to interact with sulfhydryl groups. The most
      active were the hydroxylated chalcones as their activity related to the location
      of the phenolic group in the aryl ring B as follows: o-OH>p-OH approximately 3,4
      di-OH>m-OH. These and other correlations obtained strongly contribute to the
      knowledge for design of anticandidal chalcones.

PMID- 17007966
TI  - Synthesis, structural activity relationship and anti-tubercular activity of novel
      pyrazoline derivatives.
AB  - In the present investigation, a series of 5-(-4-(substituted) phenyl)-3-(4
      hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolyl-2-toluidino methane thione and
      5-(substituted) phenyl-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolyl-2
      methoxyanilino methane thione were synthesized by the reaction between hydrazine
      hydrate and chalcones (3a-k) followed by condensation with appropriate aryl
      isothiocyanate which yielded N-substituted pyrazoline derivatives. Newly
      synthesized compounds were tested for their in vitro anti-tubercular activity
      against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system.
      Among the synthesized compounds, compound anilino-3-(4-hydroxy-3-methylphenyl)-5
      (2,6-dichlorophenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione (6i) was found to be
      more active agent against M. tuberculosis H37Rv with minimum inhibitory
      concentration of 0.0034 microM.

PMID- 17007967
TI  - [Renal manifestations in tuberous sclerosis].
AB  - BACKGROUND: Tuberous sclerosis is a rare inherited disease which can involve
      several organs. Renal involvement is one of the most severe manifestations of the
      disease. We analysed in this study renal involvement of tuberous sclerosis.
      METHODS: We studied retrospectively nine cases of tuberous sclerosis with renal
      involvement diagnosed between 1994 and 2005. The diagnosis was based on the
      presence of typical extra-renal manifestations and familial history of tuberous
      sclerosis. RESULTS: There were eight females and one male. Their mean age was
      40.8+/-16.4 years (range: 15-62). At first presentation, we noted hypertension in
      three cases, proteinuria in seven cases, hematuria in eight cases and renal
      failure in five cases (end stage renal failure in four cases). By
      ultrasonography, we found angiomyolipoma in one case, cysts in four cases and
      angiomyolipoma associated to cysts in four cases. Nephrectomy was performed in
      two patients, in one case for hydronephrosis secondary to urolithiasis and in the
      other for hemorrhagic complication. In the later, pathological examination
      revealed renal carcinoma. At last evaluation, two patients were lost to follow
      up, one had normal serum creatinine, five were on renal replacement therapy and
      the latter died from sepsis following kidney removal. CONCLUSIONS: In our
      patients, renal disease was diagnosed late at chronic renal failure stage.
      Patients with end-stage renal failure require dialysis and renal transplantation,
      but we recommend binephrectomy after starting dialysis and before transplantation
      due to the risk of cancer and bleeding related to angiomyolipomas.

PMID- 17007968
TI  - Nutritional status, perceived body image and eating behaviours in adults with
      cystic fibrosis.
AB  - BACKGROUND & AIMS: Achieving and maintaining an ideal nutritional status is the
      primary aim of the nutritional management of cystic fibrosis (CF). It is unclear
      how nutritional interventions impact on patients' perceptions and behaviours
      concerning body image and eating. This work aimed to provide a psychosocial
      profile and compare CF patients receiving (a) enteral tube feeding, (b)
      nutritional supplements, (c) no nutritional interventions, and (d) healthy
      controls. METHODS: A cross-sectional questionnaire design was employed. Age,
      gender, lung function, and body mass index were recorded. Subjects completed
      measures of eating attitudes, perceived and desired body shape, body image, self
      esteem and quality of life (QoL). RESULTS: A minority of CF patients reported
      disordered eating. Those receiving nutritional interventions engaged in less
      dieting behaviour. All CF groups, especially intervention groups, received more
      pressure from others to eat. For females, control groups desired to be slimmer
      whereas intervention groups desired to be heavier. Healthy males were content
      with their body whereas CF males wished to be heavier. Patients receiving enteral
      tube feeding were less satisfied with their body image, reported lower self
      esteem and poorer QoL. CONCLUSION: Body image and eating behaviours are important
      considerations of nutritional interventions for maintaining QoL.

PMID- 17007969
TI  - Immunization against anthrax using Bacillus subtilis spores expressing the
      anthrax protective antigen.
AB  - Protective immunity to anthrax can be achieved by antibodies raised against the
      secreted protective antigen (PA) and this forms the basis of the current
      acellular vaccines for human use. Bacillus subtilis spores have previously been
      used for delivery of heterologous antigens by the oral and nasal routes and their
      intrinsic heat-stability make them attractive vaccine vehicles. In this study we
      have expressed PA, or segments of PA, in B. subtilis using two strategies. First,
      display on the spore coat, and second, in the germinated spore (or vegetative
      cell). Using parenteral delivery we show that recombinant spores can be used to
      confer protective immunity in a murine model using an in vitro toxin
      neutralization assay and a challenge experiment with the latter showing
      protection to 100 median lethal dose of B. anthracis spores. PA must be secreted
      from the live bacterium or alternatively displayed on the spore surface to confer
      protective immunity. Intracellular expression of PA failed to confer protective
      immunity. The highest levels of protective immunity were achieved when PA was
      displayed on the spore surface as well as in the germinating spore.

PMID- 17007970
TI  - A Semliki Forest virus replicon vectored DNA vaccine expressing the E2
      glycoprotein of classical swine fever virus protects pigs from lethal challenge.
AB  - Classical swine fever virus (CSFV) causes significant losses in pig industry in
      many countries in Asia and Europe. The E2 glycoprotein of CSFV is the main target
      for neutralizing antibodies. Recently, the replicon of alphaviruses, such as
      Semliki Forest virus (SFV), has been developed as replicative expression vectors
      for gene delivery. In this study, we constructed a plasmid DNA based on SFV
      replicon encoding the E2 glycoprotein of CSFV and evaluated its efficacy in
      rabbits and pigs. The results showed that the animals immunized with the DNA
      vaccine developed CSFV-specific neutralizing antibodies and were protected from
      virulent or lethal challenge. This demonstrates that the SFV replicon-derived DNA
      vaccine can be a potential marker vaccine against CSFV infections.

PMID- 17007971
TI  - Innate antiviral resistance influences the efficacy of a recombinant murine
      cytomegalovirus immunocontraceptive vaccine.
AB  - Recombinant betaherpesviruses are attractive vaccine candidates because of their
      persistence in the host. A recombinant murine cytomegalovirus expressing the
      mouse ovarian glycoprotein zona pellucida 3 induces long lasting sterility in
      female BALB/c mice. Using inbred mouse strains selected for their innate
      resistance or susceptibility to MCMV, we show that genetically determined innate
      resistance to MCMV can reduce immunocontraceptive success. The Cmv1 locus that
      controls natural killer cell mediated responses to MCMV was implicated in
      determining vaccine efficacy. However, the role of the H-2 haplotype was less
      clear. Interestingly, Mus domesticus from an outbred colony of wild-derived mice
      were readily sterilised by vaccination, consistent with observations that strong
      innate immunity to MCMV is not common in Australian wild mice.

PMID- 17007972
TI  - Developing an ELISA using serotype-specific antigens from selected pneumococcal
      strains of own selection.
AB  - Streptococcus pneumoniae (pneumococcus) is a significant cause of morbidity and
      mortality in infants and elderly people. Pneumococcal strains possess a
      polysaccharide capsule, and 90 different serotypes have been identified. The
      pneumococcal ELISA suggested by World Health Organization (WHO) guidelines is
      based on capsular serotypes included in the 23-valent polysaccharide vaccine
      (Pneumovax((R))). Pneumococcal antigens were developed and applied in an ELISA,
      which elicited a low baseline cross-reaction with the common cell wall
      polysaccharide (C-Ps). The aim of this study was to develop an ELISA using type
      specific antigens from S. pneumoniae strains with serotypes of own selection in
      order to quantify type-specific pneumococcal antibodies in human serum.

PMID- 17007973
TI  - Ecological half-lives of 90Sr and 137Cs in terrestrial and aquatic ecosystems.
AB  - This paper describes the long-term behaviour of (90)Sr and (137)Cs in foods,
      feeds and a variety of environmental media. The long-term behaviour is quantified
      by means of the ecological half-life which integrates all processes that cause a
      decrease of activity in a given medium such as leaching, fixation and erosion. A
      large number of long-term time series of concentrations of radiocaesium and
      radiostrontium in these media have been identified and re-evaluated using a
      standardised statistical procedure to establish reference data sets of ecological
      half-lives. By example of undisturbed soils and marine water bodies it is shown
      that the ecological half-life concept is questionable if the distribution of the
      radionuclide of interest within the medium studied is non-uniform and if mixing
      and transport processes within this medium, therefore, are of considerable
      importance during the time period of observation.

PMID- 17007974
TI  - A comparison of conventional versus locking plates in intraarticular calcaneus
      fractures: a biomechanical study in human cadavers.
AB  - BACKGROUND: Internal fixation of displaced intraarticular calcaneal fractures in
      patients older than 50 years remains controversial. This is, in many cases, due
      to fear of loss of fixation and the risk of implant failure in osteoporotic bone.
      It is the objective of this study to compare the fixation strength obtained using
      calcaneal plates with and without locking screws, in the fixation of osteoporotic
      cadaveric intraarticular calcaneal fractures. METHODS: In seven pairs of fresh
      frozen lower limbs cadavers, intraarticular calcaneal fractures were created with
      a dynamic single impact loading device and stabilized using either the low
      profile locking plate, or the conventional calcaneus plate. Radiographs were
      obtained to assess reduction. The specimens were then subjected to cyclic loading
      followed by loading to failure, using matched pairs of cadaveric lower limbs. The
      Wilcoxon signed rank test was used to test for differences in the results.
      FINDINGS: The locking plate showed a significant lower irreversible deformation
      during cyclic loading and a significant higher load to failure. The difference
      between the ultimate displacement, and work to failure was not significant. A low
      bone mineral content in the area of the posterior facet correlated only in the
      conventional plate group with increased irreversible deformation. INTERPRETATION:
      This study supports the mechanical viability of using locking calcaneal plates
      for the fixation of intraarticular calcaneal fractures in elderly patients.

PMID- 17007975
TI  - Epiphytic lichens as indicators of environmental quality in Rome.
AB  - A synthesis of the studies on lichen diversity carried out in Rome over the
      period 1982-2003 is presented. In this work, the Lichen Diversity (LD) method has
      been applied. Besides air pollution, the most important variable affecting the
      epiphytic lichen flora of Rome, currently updated to 102 taxa, is the influence
      of the Tyrrhenian Sea. Significant changes in the lichen flora have been noted
      over the past 20 years, with the lowest diversity now being found in the urban
      centre and in the eastern and southern sectors, while the "lichen desert" area
      has decreased in parallel with decreasing concentrations of CO, NO(x) and SO2.

PMID- 17007976
TI  - Possible interaction between MAOA and DRD2 genes associated with antisocial
      alcoholism among Han Chinese men in Taiwan.
AB  - Both monoamine oxidase A (MAOA) and dopamine D(2) receptor (DRD2) genes have been
      considered as candidate genes for antisocial personality disorder with alcoholism
      (Antisocial ALC) [Parsian, A., 1999. Sequence analysis of exon 8 of MAO-A gene in
      alcoholics with antisocial personality and normal controls. Genomics. 45, 290
      295.; Samochowiec, J., Lesch, K.P., Rottmann, M., Smolka, M., Syagailo, Y.V.,
      Okladnova, O., Rommelspacher, H., Winterer, G., Schmidt, L.G., Sander, T., 1999.
      Association of a regulatory polymorphism in the promoter region of the monoamine
      oxidase A gene with antisocial alcoholism. Psychiatry. Res. 86, 67-72.; Schmidt,
      L.vG., Sander, T., Kuhn, S., Smolka, M., Rommelspacher, H., Samochowiec, J.,
      Lesch, K.P., 2000. Different allele distribution of a regulatory MAO-A gene
      promotor polymorphism in antisocial and anxious-depressive alcoholics. J. Neural
      .Transm. 107, 681-689.]. However, the association between alcoholism and MAOA or
      DRD2 gene has not been universally accepted [Lee, J.F., Lu, R.B., Ko, H.C.,
      Chang, F.M., Yin, S.J., Pakstis, A.J., Kidd, K.K., 1999. No association between
      DRD(2) locus and alcoholism after controlling the ADH and ALDH genotypes in
      Chinese Han population. Alcohol. Clin. Exp. Res. 23, 592-599.; Lu, R.B., Lin,
      W.W., Lee, J.F., Ko, H.C., Shih, J.C., 2003. Neither antisocial personality
      disorder nor antisocial alcoholism association with MAOA gene among Han Chinese
      males in Taiwan. Alcohol. Clin. Exp. Res. 27, 889-893.]. Since dopamine is
      metabolized to 3,4-dihydroxyphenyl-acetaldehyde (DOPAL) via monoamine oxidase
      (MAO) [Westerink, B.H., de Vries, J.B., 1985. On the origin of dopamine and its
      metabolite in predominantly noradrenergic innervated brain areas. Brain. Res.
      330, 164-166.], the interaction between MAOA and DRD2 genes might be related to
      Antisocial ALC. The present study aimed to determine whether Antisocial ALC might
      be associated with the possible interactions of DRD2 gene with MAOA gene. Of the
      231 Han Chinese subjects who were recruited for the study, 73 participants were
      diagnosed with Antisocial ALC and 158 subjects were diagnosed with antisocial
      personality disorder without alcoholism (Antisocial Non-ALC). The DRD2 TaqI A and
      MAOA-uVNTR (variable number of tandem repeat located upstream) polymorphisms were
      not found to be associated with Antisocial ALC. However, an association between
      DRD2 TaqI A polymorphisms and Antisocial ALC was shown only after stratification
      for the MAOA-uVNTR 4-repeat polymorphism. Additionally, after multiple logistic
      regressions, we found that, under stratification of MAOA-uVNTR 4-repeat
      polymorphism and in comparison with the DRD2 A1/A1 genotype as a reference group,
      the DRD2 A1/A2 genotype has a possible protective effect against alcoholism in
      individuals with antisocial personality disorder (ASPD). We concluded that the
      possible interactions between MAOA-uVNTR polymorphism and DRD2 TaqI A
      polymorphism might be related to Antisocial ALC among Han Chinese men in Taiwan.

PMID- 17007977
TI  - Psychopharmacologic treatment of aggressive preschoolers: a chart review.
AB  - Very young children with severe aggression are a growing focus of care in child
      psychiatry. Notwithstanding diagnostic uncertainties in this age group,
      medication, not usually considered a first-line intervention, is becoming a
      treatment option for a growing number of clinicians in spite of a dearth of
      research in this area. This chart review assessed the patient characteristics,
      diagnoses and treatment responses of aggressive preschoolers who were treated in
      a university child psychiatry outpatient clinic from 2001-2004. The most common
      diagnoses were Attention Deficit Hyperactivity Disorder (ADHD), Disruptive
      Behavior Disorder and Posttraumatic Stress Disorder (PTSD). Medication was
      prescribed for a majority of the children with prominent aggression; atypical
      antipsychotics were prescribed with the greatest frequency, followed by
      stimulants and then alpha agonists--treatment response ratings indicated moderate
      to marked improved in a majority of the preschoolers who received one or a
      combination of these medications. Findings support the need for controlled trials
      of medication in preschoolers with severe aggression.

PMID- 17007978
TI  - [The lymphatic malformations: clinical aspects and evolution].
AB  - Lymphatic malformations (LM) are the most frequent vascular malformations. There
      are three types of lesions involving lymphatic development that must be included
      in LM: vascular anomalies and knots (truncal malformations [TLM]); cystic
      anomalies, superficial or deep, uni- or multicystic (extratruncal malformations
      [ETLM]) and hemolymphatic anomalies which combine venous, arterial, or capillary
      malformations with LM. ETLM can be ubiquitously distributed but most are located
      in the cervical or axillary regions. Most ETLM are diagnosed at birth and in 80
      90% of the cases before the age of 2. The clinical aspects are extremely
      variable: superficial ETLM (vesicular) and deep ETLM, localised or diffuse, mono-
      or multicystic. TLM are generally located on a lower limb with neonatal lymphatic
      oedema (often in a polymalformation context). All forms of the hemolymphatic
      combination can be identified. They are generally located on the limbs and are
      often unilateral. They are usually sporadic but can also be can be found in
      polymalformation syndromes (Klippel-Trenaunay, Parkes-Weber, Protee, Maffucci).
      ETLM generally tend to increase in volume and spread with age with stabilisation
      at puberty. They do not tend to spontaneously regress. Specific local
      complications can have serious consequences. They are linked to haemorrhaging,
      infections and compression phenomena. There can also be complications such as
      skeletal and soft tissue hypertrophy.

PMID- 17007979
TI  - [Surgical treatment of lymphatic malformations].
AB  - Lymphatic malformations remain a therapeutic challenge. Many treatments by the
      past led to poor success. The wide variety of clinical presentations makes it
      difficult to outline specific management programs. Often, diagnosis or
      complication circumstances as infection, bleeding, airway obstruction, or
      handicap force acting. Thus, a specific follow-up joined to a multidisciplinary
      analysis are the key of well-planned surgery. Through our experience and a review
      of literature, we will describe principles of lymphatic malformations surgery and
      specific technics for specific locations.

PMID- 17007980
TI  - [Clinical aspects of capillary malformations].
AB  - Capillary malformations (CM) are defects of the dermal capillary bed. These slow
      flow malformations can affect any part of the body and are always lateralized,
      despite Unna's naevus. Present at birth, they grow proportionally with the child.
      In rare instance, they can be part of a more complex syndrome such as Sturge
      Weber syndrome. Ectatic CMs of telangiectatic types can be cutaneous, isolated,
      multiples, diffuse or generalized. In rare instance, they can be associated with
      epidermal modifications. They can also be part of a syndrome such as Fabry
      disease, Osler-Weber-Rendu disorder or Cutis marmorata telangiectatica congenita
      (CMTC). This chapter details the various clinical aspects of CMs.

PMID- 17007981
TI  - [Endovascular management of arteriovenous malformations].
AB  - Management of high-flow arteriovenous malformation remain often problematic.
      Complete eradication of the nidus is the only potential cure, but this, however,
      is often difficult if not impossible. Frequently, a multidisciplinary approach is
      required. In these article, techniques and results of the endovascular management
      of MAV are discussed.

PMID- 17007982
TI  - [Indications of lasers treatment for lymphatic malformations].
AB  - Cutaneous dermatologic lesions of LM, in type of superficial, translucent,
      localized or diffuse vesicles, are accessible to laser treatment. The useful
      lasers are essentially laser CO(2), and rarely pulsed dye laser and the Nd: YAG.
      Treatment by laser allows to obtain the ablation of vesicles by limiting
      aftereffects (scare) and so to dry up the transcutaneous lymphatic liquid.
      However laser has no action on the deep constituent of the LM and it's why medium
      and long term recurrences are inevitable. Finally, the indication of the laser
      must be retained only as a supplement to the surgery and has to be done by
      experimented persons.

PMID- 17007983
TI  - [Percutaneous treatment of venous malformations].
AB  - Percutaneous sclerotherapy under fluoroscopic guidance can be used to treat
      venous malformations, in order to reduce the lesion's size and associated pain,
      to improve fonctional impairment or esthetic prejudice. Although this treatment
      modality seems to be simple, a multidisciplinary approach and rigorous technique
      is required to avoid serious complications. Technical details, the various
      sclerosing agents, possible complications and results are reviewed.

PMID- 17007984
TI  - [Venous malformations: clinical characteristics and differential diagnosis].
AB  - Venous malformations (VM) are localized defects of blood vessels that are due to
      vascular dysmorphogenesis. These slow-flow lesions can affect any tissue or
      organ. Clinically, a cutaneous VM is characterized by a bluish mass that is
      compressible on palpation. Phleboliths are commonly present. Symptoms depend on
      location and size. VM are often sporadic and isolated, however, they can be
      associated with other malformations and be part of a syndrome; Klippel-Trenaunay
      (capillary-lymphatico-venous malformation with limb hypertrophy) is the most
      common. Glomuvenous malformation (GVM) is another type of venous anomaly. In
      contrast to VM, GVM is often painful on palpation and not compressible. Clinical
      diagnosis of VM is often made in the presence of a bluish cutaneous lesion:
      however, other lesions can mimick VM. The most frequent anomalies are a blue
      naevus, a hemorrhagic lymphatic malformation, a sub-cutaneous hemangioma or even
      the presence of dilated superficial normal veins due to underlying venous
      stenoses. This chapter will detail the clinical characteristics of venous
      anomalies and their differential diagnosis.

PMID- 17007985
TI  - [Infantile hemangiomas: differential diagnosis and associated anomalies].
AB  - Infantile hemangiomas are frequent benign vascular tumors that are often easily
      recognized. However, the diagnosis between infantile hemangiomas and other
      vascular tumors, whether benign or malignant, may be difficult. This chapter
      describes the different clinical presentations of hemangiomas and details the
      investigations that are needed to confirm the nature of the lesion and to
      diagnose the potentially associated anomalies. Knowledge on differential
      diagnosis enables clinicians to detect hemangiomas that can lead to complications
      and that necessitate a multidisciplinary approach.

PMID- 17007986
TI  - [Surgical treatment of arteriovenous malformations].
AB  - MAV surgery remains still today one of most difficult in the surgery of vascular
      malformations. Embolisation the most selective possible follow-up of a surgical
      removal carrying the totality of the nidus is the only effective treatment.
      Usually, MAV of small size, quiescent, should not be operated, the surgery being
      reserved for the evolutionary or complicated forms. This surgical procedure must
      allow the complete eradication of the lesion without which the cure is not
      possible. The incomplete removal causes repetition, sometimes aggravation with,
      sometimes, life threatening problems.

PMID- 17007987
TI  - Human paraoxonase: a promising approach for pre-treatment and therapy of
      organophosphorus poisoning.
AB  - The limited efficiency of medical countermeasures against poisoning by nerve
      agent justifies efforts to find new prophylactic means and new antidotes. The
      concept of bioscavengers has emerged as an alternative approach to
      pharmacological pre- and post-exposure treatments. Catalytic scavengers are
      enzymes displaying a turnover with OPs as substrates, allowing rapid and
      efficient protection using administration of small doses. Several reasons have
      endorsed human paraoxonase (PON1) to be a pertinent candidate as catalytic
      bioscavenger. The physiological function of PON1 has not yet been unambiguously
      identified. Considered as a promiscuous enzyme, PON1 appears to be primarily a
      lactonase and also displays an anti-atherogenic activity closely linked to its
      localization on HDL particles. A HDL-associated phosphate transporter termed
      human phosphate binding protein (HPBP) was found to be a partner of natural human
      PON. In the absence of its natural environment (or mimicry by detergents), human
      PON1 is unstable and tends to aggregate. Converging data indicate that both the
      activity and the stability of PON1 are dramatically dependent on the HDL
      component molecular environment, including HPBP. Therefore, biochemical and
      physiological characterization of PON1-HPBP complexes, the environment allowing
      retaining functional enzyme state(s), and the thermal and storage stability of
      PON1 are mandatory. Synergistic efforts on characterization of recombinant hybrid
      PON1 expressed in E. coli and natural human PON1 provide information for the
      future rational design of stable mutants of PON1-based catalytic scavengers to be
      used as safe and effective countermeasures to OP intoxication.

PMID- 17007988
TI  - Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in
      female goat offspring.
AB  - The aim of this study was to investigate if environmentally relevant doses of the
      putative estrogenic non dioxin-like PCB 153 and the dioxin-like PCB 126 caused
      changes in bone tissue in female goat offspring following perinatal exposure.
      Goat dams were orally dosed with PCB 153 in corn oil (98 microg/kg body wt/day)
      or PCB 126 (49 ng/kg body wt/day) from day 60 of gestation until delivery. The
      offspring were exposed to PCB in utero and through mother's milk. The suckling
      period lasted for 6 weeks. Offspring metacarpal bones were analysed using
      peripheral quantitative computed tomography (pQCT) after euthanisation at 9
      months of age. The diaphyseal bone was analysed at a distance of 18% and 50% of
      the total bone length, and the metaphyseal bone at a distance of 9%. Also,
      biomechanical three-point bending of the bones was conducted, with the load being
      applied to the mid-diaphyseal pQCT measure point (50%). PCB 153 exposure
      significantly decreased the total cross-sectional area (125 mm(2)+/-4) versus non
      exposed (142 mm(2)+/-5), decreased the marrow cavity (38 mm(2)+/-4) versus non
      exposed (50 mm(2)+/-3) and decreased the moment of resistance (318 mm(3)+/-10)
      versus non-exposed (371 mm(3)+/-20) at the diaphyseal 18% measure point. At the
      metaphyseal measure point, the trabecular bone mineral density (121 mg/cm(3)+/-5)
      was increased versus non-exposed (111 mg/cm(3)+/-3). PCB 126 exposure did not
      produce any observable changes in bone tissue. The biomechanical testing of the
      bones did not show any significant changes in bone strength after PCB 153 or PCB
      126 exposure. In conclusion, perinatal exposure to PCB 153, but not PCB 126,
      resulted in altered bone composition in female goat offspring.

PMID- 17007989
TI  - (+/-)-2-Chloropropionic acid elevates reactive oxygen species formation in human
      neutrophil granulocytes.
AB  - (+/-)-2-Chloropropionic acid (2-CPA) is a neurotoxic compound which kills
      cerebellar granule cells in vivo, and makes cerebellar granule cells in vitro
      produce reactive oxygen species (ROS). We have studied the effect of 2-CPA on ROS
      formation in human neutrophil granulocytes in vitro. We found an increased
      formation of ROS after 2-CPA exposure using three different methods; the
      fluorescent probe DCFH-DA and the chemiluminescent probes lucigenin and luminol.
      Four different inhibitors of ROS formation were tested on the cells in
      combination with 2-CPA to characterize the signalling pathways. The spin-trap s
      PBN, the ERK1/2 inhibitor U0126 and the antioxidant Vitamin E inhibited the 2-CPA
      induced ROS formation completely, while the mitochondrial transition permeability
      pore blocker cyclosporine A inhibited the ROS formation partly. We also found
      that 2-CPA induced an increased nitric oxide production in the cells by using the
      Griess reagent. The level of reduced glutathione, measured with the DTNB assay,
      was decreased after exposure to high concentrations of 2-CPA. Western blotting
      analysis showed that 2-CPA exposure led to an elevated phosphorylation of ERK MAP
      kinase. This phosphorylation was inhibited by U0126. Based on these experiments
      it seems like the mechanisms for 2-CPA induced toxicity involves ROS formation
      and is similar in neutrophil granulocytes as earlier shown in cerebellar granule
      cells. This also implies that 2-CPA may be immunotoxic.

PMID- 17007990
TI  - Distribution and genetic diversity of bacterial thiopurine methyltransferases in
      soils emitting dimethyl selenide.
AB  - Dimethyl selenide (DMSe) and dimethyl diselenide (DMDSe) emissions by soil
      samples spiked with selenite or (methyl)selenocysteine, with or without a
      supplement of nutrient broth and glucose were measured. DMSe was the main form of
      volatile Se produced, and was observed for both Se-substrates. DMDSe was only
      emitted from soils spiked with (methyl)selenocysteine. Two bacterial thiopurine
      methyltransferases (TPMTs), TPMT-I and TPMT-E, have been reported to be involved
      in DMSe and DMDSe emissions [J. Bacteriol. 184 (2002) 3146; Appl. Environ.
      Microbiol. 69 (2003) 3784]. To establish if these TPMTs or other members of their
      gene family could have contributed to the DMSe emissions observed, the diversity
      of bTPMT gene (tpm) sequences among the soils of this study was investigated.
      Total DNAs from these soils were extracted and screened using the tpm PTCF2-PTCR2
      consensus primers defined to PCR amplify this gene family. The PCR products
      obtained from two soils were cloned, analysed by PCR-RFLP, and sequenced. Their
      analysis showed an important diversity of tpm lineages (around 12) in soils.
      Phylogenetic analysis of the deduced TPMT sequences of these soils revealed
      lineages not previously recorded in the databases, sequences closely related or
      identical to freshwater TPMTs, or sequences encoding TPMTs closely related to
      those of Pseudomonas fragi TPMT-K, Pseudomonas Hsa.28 TPMT-I, or Colwellia
      psychrerythraea TPMT-Z. Nested PCRs, allowing detection of about 13 distinct tpm
      soil and freshwater lineages by PTCF2-PTCR2 PCR screenings, were performed on the
      soil total DNAs. These PCRs confirmed the sequencing data, and allowed to recover
      lineages not detected by the cloning strategy. These results indicate that soils,
      like the freshwater samples, harbour TPMT-I gene sequences but may also have
      distinct tpm lineages. This study further supports our hypothesis that TPMTs
      contribute to DMSe soil emissions.

PMID- 17007991
TI  - An interdisciplinary approach to investigate the impact of cobalt in a human
      keratinocyte cell line.
AB  - Since in nuclear power plants, risks of skin contact contamination by radiocobalt
      are significant, we focused on the impact of cobalt on a human cutaneous cell
      line, i.e. HaCaT keratinocytes. The present paper reports an interdisciplinary
      approach aimed at clarifying the biochemical mechanisms of metabolism and
      toxicity of cobalt in HaCaT cells. Firstly, a brief overview of the used
      instrumental techniques is reported. The following parts present description and
      discussion of results concerning: (i) toxicological studies concerning cobalt
      impact towards HaCaT cells (ii) structural and speciation fundamental studies of
      cobalt-bioligand systems, through X-ray absorption spectroscopy (XAS), ab initio
      and thermodynamic modelling (iii) preliminary results regarding intracellular
      cobalt speciation in HaCaT cells using size exclusion chromatography/inductively
      coupled plasma-atomic emission spectroscopy (SEC/ICP-AES) and direct in situ
      analysis by ion beam micropobe analytical techniques.

PMID- 17007992
TI  - Iodine transfers in the coastal marine environment: the key role of brown algae
      and of their vanadium-dependent haloperoxidases.
AB  - Brown algal kelp species are the most efficient iodine accumulators among all
      living systems, with an average content of 1.0% of dry weight in Laminaria
      digitata, representing a ca. 30,000-fold accumulation of this element from
      seawater. Like other marine macroalgae, kelps are known to emit volatile short
      lived organo-iodines, and molecular iodine which are believed to be a main vector
      of the iodine biogeochemical cycle as well as having a significant impact on
      atmospheric chemistry. Therefore, radioactive iodine can potentially accumulate
      in seaweeds and can participate in the biogeochemical cycling of iodine, thereby
      impacting human health. From a radioecological viewpoint, iodine-129 (129I, half
      life of 1.6 x 10(7) years) is one of the most persistent radionuclide released
      from nuclear facilities into the environment. In this context, the speciation of
      iodine by seaweeds is of special importance and there is a need to further
      understand the mechanisms of iodine uptake and emission by kelps. Recent results
      on the physiological role and biochemistry of the vanadium haloperoxidases of
      brown algae emphasize the importance of these enzymes in the control of these
      processes.

PMID- 17007993
TI  - Leptin levels in serum depending on Body Mass Index in patients with endometrial
      hyperplasia and cancer.
AB  - Leptin levels in serum depending on Body Mass Index (BMI) in patients with
      endometrial hyperplasia and cancer. OBJECTIVES: Concentrations of leptin, a
      hormone secreted by white adipose tissue, correlate strongly with body mass.
      Leptin interacts with several other hormones, modifies the activities of some
      enzymes and proinflammatory cytokines, participates in hematopoiesis,
      thermogenesis, and angiogenesis, and is involved in the control of carbohydrate
      and lipid metabolism. This study was undertaken to determine whether serum
      concentrations of leptin in obese patients with endometrial hyperplasia and
      cancer deviate from values in patients with normal endometrium. STUDY DESIGN: We
      enrolled 86 obese postmenopausal women, including 40 with endometrial cancer and
      hyperplasia and 46 with normal endometrium. Depending on BMI, three subgroups
      were formed: I<30; II = 30-40; III > 40. Leptin concentrations were measured with
      immunoenzymatic test kits from IBL. Statistical comparison was done with the chi
      square (chi(2)) test and Statistica software package. RESULTS: Mean serum
      concentration of leptin in endometrial cancer and hyperplasia was 16737.1 pg/ml
      as opposed to 9048.7 pg/ml in patients without endometrial pathology (p<0.0001).
      Significantly, higher concentrations of leptin were noted in every BMI subgroup
      of patients with endometrial pathology in comparison to controls (p<0.005).
      CONCLUSIONS: Leptin appears to participate in proliferative processes of the
      endometrium. Obesity is an important risk factor in endometrial cancer.

PMID- 17007994
TI  - Translational and rotational motions of proteins in a protein crowded
      environment.
AB  - Fluorescence correlation spectroscopy (FCS) was used to measure the translational
      diffusion of labeled apomyoglobin (tracer) in concentrated solutions of
      ribonuclease A and human serum albumin (crowders), as a quantitative model system
      of protein diffusive motions in crowded physiological environments. The ratio of
      the diffusion coefficient of the tracer protein in the protein crowded solutions
      and its diffusion coefficient in aqueous solution has been interpreted in terms
      of local apparent viscosities, a molecular parameter characteristic for each
      tracer-crowder system. In all protein solutions studied in this work, local
      translational viscosity values were larger than the solution bulk viscosity, and
      larger than rotational viscosities estimated for apomyoglobin in the same
      crowding solutions. Here we propose a method to estimate local apparent
      viscosities for the tracer translational and rotational diffusion directly from
      the bulk viscosity of the concentrated protein solutions. As a result of this
      study, the identification of protein species and the study of hydrodynamic
      changes and interactions in model crowded protein solutions by means of FCS and
      time-resolved fluorescence depolarization techniques may be expected to be
      greatly simplified.

PMID- 17007995
TI  - Antiandrogens in the treatment of prostate cancer.
AB  - OBJECTIVES: To give an overview on the contemporary role of antiandrogens in
      prostate cancer treatment. METHODS: A review of the literature was performed
      concerning pharmacologic properties, possible indications and side effects of
      antiandrogens in the treatment of early and advanced prostate cancer. RESULTS:
      One steroidal and three non-steroidal antiandrogens are in common use for the
      treatment of prostate cancer. Monotherapy with non-steroidal antiandrogens may
      prevent osteoporosis, loss of musculature and may preserve sexual activity in a
      proportion of patients and therefore has advantages in quality of life compared
      to castration. In patients with localized disease managed by watchful waiting or
      in an adjuvant setting, there are no studies showing an advantage in early versus
      delayed treatment with antiandrogens regarding clinical progression. In locally
      advanced non-metastatic prostate cancer, antiandrogen monotherapy seems to be an
      alternative to castration treatment if treatment is required. In patients with
      metastatic disease and a high tumor burden, antiandrogen monotherapy is inferior
      to castration. In advanced disease, combined androgen blockade can provide a
      small survival advantage, which, however, has to be balanced against increased
      side effects and costs. CONCLUSIONS: Antiandrogens are a treatment option in some
      patients with prostate cancer. However, it has to be taken into account that the
      hormonal effect is inferior to castration.

PMID- 17007996
TI  - Current indications for chemotherapy in prostate cancer patients.
AB  - Recently, data from two randomized studies, TAX327 and SWOG 9916, which compared
      docetaxel-based chemotherapy to mitoxantrone-based therapy, have demonstrated
      that treatment with docetaxel can prolong life in a statistically significant way
      in patients with hormone refractory prostate cancer (HRPC). In the TAX237 trial
      the median overall survival rates for patients treated with docetaxel every 3 wk
      was 18.9 mo, compared with 16.4 mo for the patients in the control arm (p=0.009).
      Patients treated with the combination of docetaxel and estramustine in the SWOG
      trial had a significant improvement in median survival (18 mo vs 16 mo, p=0.01),
      longer progression-free survival (6 mo compared with 3 mo, p<0.0001), and a 20%
      reduction in the risk of death. The optimal timing of docetaxel-based
      chemotherapy is still unknown because there are no prospective clinical trials
      indicating whether earlier treatment is more effective than delayed treatment.
      There are now increasing options also for second-line therapies in the palliative
      treatment of HRPC, and ongoing studies on new drugs such as satraplatin and
      ixabepilone will define the role of these agents in this setting. Preliminary
      neoadjuvant and adjuvant chemotherapy studies in high-risk prostate cancer
      patients have demonstrated that these approaches are feasible and do not add
      morbidity to surgery or radiotherapy, but their impact on survival still needs to
      be proven in randomized studies.

PMID- 17007997
TI  - Presence of LDL modified by myeloperoxidase in the penis in patients with
      vascular erectile dysfunction: a preliminary study.
AB  - OBJECTIVE: Erectile dysfunction (ED) is a major vascular disorder.
      Atherosclerosis is closely related to lipoprotein metabolism and especially,
      oxidative modifications of low-density lipoproteins (LDLs), which are involved in
      early development of the atherosclerotic lesions. Current major questions include
      how LDLs are oxidised (OxLDL) in vivo. Myeloperoxidase (MPO) is an enzyme present
      in the azurophile granules of neutrophils and monocytes that can contribute to
      LDL oxidation in the presence of H(2)O(2). We have developed a new monoclonal
      antibody against LDL modified by MPO (Mox-LDL) and have used it on penile
      biopsies from patients operated on for penile implant. METHODS: Seven patients
      with vascular ED and one impotent patient after radical prostatectomy (RP)
      underwent biopsy of the cavernous body during penile implant procedures. An
      immunohistochemical study with a monoclonal antibody against Mox-LDL and an
      antibody against apoprotein B (ApoB), the protein moiety of LDL, to confirm the
      presence of LDL was performed. RESULTS: The staining was positive for Mox-LDL and
      ApoB and was present between the endothelial cells of the sinusoid spaces and the
      smooth muscle cells in the seven patients with vascular ED. The patient with RP
      was negative for Mox-LDL. DISCUSSION: Because it is known that modified LDL could
      decrease nitric oxide production, Mox-LDL could be one of the agents responsible
      for ED. Further studies are needed to confirm this hypothesis.

PMID- 17007998
TI  - Molecular cloning and characterization of rat brain endothelial cell derived gene
      1 (tumor suppressor candidate 5) expressing abundantly in adipose tissues.
AB  - We report the cloning and expressional analysis of rat brain endothelial cell
      derived gene-1 (BEC-1), detected as a gene dominantly expressed in rat brain
      endothelial cells by the use of suppression subtractive hybridization technique.
      The complementary deoxyribonucleic acid sequence of BEC-1 messenger ribonucleic
      acid was completely determined with a full length of 3410 bp. The open reading
      frame within the sequence consisted of 522 bp, and the predicted protein sequence
      was 173 amino acid residues. BEC-1 gene was thought to be rat tumor suppressor
      candidate 5 (TUSC5), since BEC-1 had considerable homology with both mouse TUSC5
      and human located at 17-p-13 point three 1 (LOST1) categorized as human TUSC5
      (identities of 97% and 85%, respectively), which were recently identified as a
      novel tumor suppressor gene candidate. Expressional analyses for BEC-1 mRNA with
      real-time PCR and of BEC-1 protein by Western blotting demonstrated that both
      were dominantly expressed in the adipose tissues of Sprague-Dawley (SD) rats. We
      analyzed and compared the differential expressions of BEC-1 (TUSC5) mRNA and
      protein in fat tissues between obese homozygous (fa/fa) and lean wild-type (+/+)
      Zucker rats. Both expressions in the epididymal white adipose tissue (WAT) were
      highest, followed by those in the interscapular brown adipose tissue (BAT),
      subcutaneous, and mesenteric WATs, respectively. Interestingly, both expressions
      in epididymal WAT of obese Zucker rats were significantly lower than those in
      lean rats. Although cold exposure at 4 degrees C for 6 h significantly stimulated
      uncoupling protein-1 (UCP-1) mRNA expression, it significantly inhibited BEC-1
      (TUSC5) mRNA expression in the interscapular BAT. These data indicated that rat
      BEC-1 (TUSC5) was abundantly expressed in adipose tissues, and that it might be
      involved in their regulation independently of UCP-1.

PMID- 17007999
TI  - Removal of ammonium from wastewater using calcium form clinoptilolite.
AB  - The paper concerns the removal of ammonium ions from aqueous solution using a
      modified clinoptilolite-Ca(2+)-formed clinoptilolite (CaY) prepared from natural
      clinoptilolite. The batch study results show that the pH has an effect on
      ammonium adsorption capacity as it can influence both the character of the
      exchanging ions and the clinoptilolite itself; the CaY has a high selectivity to
      NH(4)(+) and the exchange decreases with increasing temperature; ammonium ion
      uptake onto CaY was suitably described by the Langmuir model. The column results
      indicated that the effluent of simulated wastewater treated with CaY could meet
      the integrated wastewater discharge standard of China, and CaY can be circulated
      through regenerating by Ca(OH)(2).

PMID- 17008000
TI  - Catalytic combustion of ethyl acetate on supported copper oxide catalysts.
AB  - Total oxidation of ethyl acetate on supported copper oxide catalysts was
      investigated. The catalysts have been prepared by wet impregnation method and
      characterized by XRD, TEM and XPS. Among the catalysts with the supports of TiO2,
      CeO2/TiO2 and CeO2-ZrO2/TiO2, CeO2-ZrO2 solid solutions doped TiO2 supported
      catalyst gives the highest catalytic activity. Catalyst with the composition of 5
      wt.% CuO/10 wt.% CeO2-ZrO2-TiO2 shows the total oxidation of ethyl acetate at
      about 270 degrees C with the 100% CO2 selectivity. The characterization studies
      of supported copper oxide catalysts showed that the highly dispersed CuO is one
      of the active phase which contacts intimately with the support, the action of the
      interface between the components was not be ignored.

PMID- 17008001
TI  - Industrial and simulation analysis of the nitrogen trichloride decomposition
      process in electrolytic chlorine production.
AB  - This work presents the dynamic simulation of the thermal decomposition of
      nitrogen trichloride (NCl(3)) during electrolytic chlorine (Cl(2)) production,
      using an industrial plant as a case study. NCl(3) is an extremely unstable and
      explosive compound and the decomposition process has the following main problems:
      changeability of the reactor temperature and loss of solvent. The results of this
      work will be used to establish a more efficient and safe control strategy and to
      analyze the loss of solvent during the dynamic period. The implemented model will
      also be used to study the use of a new solvent, considering that currently used
      solvent will be prohibited from commercial use in 2010. The process was simulated
      by using the commercial simulator Aspen and the simulations were validated with
      plant data. From the results of the simulation it can be concluded that the rate
      of decomposition depends strongly on the temperature of the reactor, which has a
      stronger relationship to the liquid Cl(2) (reflux) and gaseous Cl(2) flow rates
      which feed the system. The results also showed that the loss of solvent changes
      strongly during the dynamic period.

PMID- 17008002
TI  - Reuse of waste silica as adsorbent for metal removal by iron oxide modification.
AB  - Silica gel is widely used in research laboratories, especially for the
      purification of organic compounds. Consequently, waste silica gel is generated in
      increasing amounts. In this work, waste silica was modified by coating its
      surface with iron oxide aiming to obtain an effective adsorbent for metal removal
      from wastewater. In the preparation of the adsorbent, the optimal pretreatment
      temperature and iron concentration were investigated. The coated waste silica was
      characterized for BET surface area, pore size, specific pore volume and iron
      content. Iron oxide-coated waste silica was tested for the adsorption of Pb(II),
      Cu(II), Cd(II) and Ni(II) from solutions in a batch system. The effect of contact
      time, pH and salt concentration on metal adsorption was investigated. It was
      found that the adsorption of metals occurred rapidly and reached equilibrium
      within 30 min. The pH suitable for metal adsorption was between 6 and 7 and
      leaching of iron from the coating was observed only at pH 3 or lower. The
      presence of salt reduced the adsorption efficiency of the adsorbent. The
      adsorption behavior followed both Langmuir and Freundlich isotherms (25 degrees
      C). Finally, the efficacy of the adsorbents was investigated using aqueous lab
      waste where removal efficiencies ranging from 62 to 89% were achieved when the
      initial metal concentrations ranged from 13 to 42 mg L(-1).

PMID- 17008003
TI  - The metal-leaching and acid-neutralizing capacity of MSW incinerator ash co
      disposed with MSW in landfill sites.
AB  - Municipal solid waste (MSW) incinerator (MSWI) bottom ash and fly ash were used
      as landfill cover or were co-disposed with MSW to measure their potential metal
      releasing and acid-neutralizing capacity (ANC) in landfill sites. Five lysimeters
      (height 1.2m, diameter 0.2m), simulating landfill conditions, were used in the
      experiment. Four contained either bottom ash (BA) or fly ash (FA) with BA:MSW
      ratios of 100 and 200 g L(-1) and FA:MSW ratios of 10 and 20 g L(-1), and the
      fifth was the control, which contained no ash. The lysimeters were arranged so as
      to contain four layers, with BA or FA placed on top of MSW within each layer.
      Each lysimeter was recirculated with 100mL leachate using peristaltic pumps, and
      100mL of the leachate was collected weekly to measure the soluble metal
      concentrations. The results showed that the concentrations of soluble alkali
      metals measured in the leachate were in the order Ca>K>Na>Mg. In addition, the
      concentrations of soluble alkali metals of Ca and K collected from the lysimeters
      containing FA were found to be higher than the concentrations from the lysimeters
      containing BA. The concentrations of heavy metals (Cd, Cr, Cu, Ni, and Zn) were
      found to be <1 mg L(-1) except for Pb, which reached 2 mg L(-1). These results
      suggest that for alkali metals there might be an ANC consistent with the results
      of an acid titration curve, which would provide suitable conditions for anaerobic
      digestion of the MSW in the landfill. Furthermore, heavy metals and trace metals
      were found in concentrations, which were too low to exert inhibitory effects on
      anaerobic digestion, and thus they could serve as micronutrients to exert
      beneficial rather than detrimental effects on landfill biostabilization.

PMID- 17008004
TI  - Comparative investigation of N,N'-bis-(dithiocarboxy)piperazine and
      diethyldithiocarbamate as precipitants for Ni(II) in simulated wastewater.
AB  - The performances of a coordination polymerization precipitant, N,N'-bis
      (dithiocarboxy)piperazine (BDP) were compared with the widely used heavy metal
      precipitant, diethyldithiocarbamate (DDTC), through the treatment of three kinds
      of nickel-containing wastewaters, NiSO(4), nickel citrate (NiCA) and Ni(2+)-dye.
      Results indicated that both BDP and DDTC at their stiochiometric doses could
      reduce 50.00 mg l(-1) free nickel(II) to lower than 1.0 mg l(-1) (discharge limit
      of nickel ions in China) and 10% precipitants doses increase could treat NiCA
      containing 50.00 mg l(-1) Ni(2+) to meet the discharge limit. But [NiBDP](n)
      coordination polymerization precipitates had more rapid settling speed than
      Ni(DDTC)(2) precipitates. It was also observed that BDP could still partly remove
      Reactive Brilliant Red X-3B from Ni(II)-dye integrated wastewater through the
      adsorption of the precipitates [NiBDP](n), in addition to precipitating Ni(II). A
      1:1 stiochiometric dose of BDP/Ni(II) could decrease Ni(II) from 50.00 to 0.87 mg
      l(-1), and simultaneously reduce the dye from 30.00 to 19.52 mg l(-1).

PMID- 17008005
TI  - Fenton-enhanced gamma-radiolysis of cyanuric acid.
AB  - Degradation of cyanuric acid (OOOT), a stable end product of oxidative
      decomposition of atrazine, is investigated in a combined field of gamma
      radiolysis and fenton reaction. The reaction of hydroxyl radical (OH) at pH 6 was
      carried out by irradiating N(2)O saturated aqueous solutions containing OOOT (1 x
      10(-3) mol dm(-3)), and this resulted only a marginal degradation (20%). However,
      when the same reaction was carried out in the presence of varying concentrations
      of ferrous sulfate ((5-10)x10(-5) mol dm(-3)), the decay of OOOT has been
      enhanced to more than 80%. This decay followed a first order kinetics. Nearly
      similar effects were observed with another triazine derivative, 2,4
      dioxohexahydro-1,3,5-triazine (DHT). Two major reaction mechanisms are proposed
      for the enhanced decay of OOOT. The formation of unstable hydroxyl radical
      adducts from the reaction of .OH which is the result of gamma radiolysis and the
      Fenton reaction (resulting from the reaction of the added Fe(II) and of the
      H(2)O(2) from the radiolysis of water), is proposed as the first mechanism. The
      second mechanism, which is likely the major contributor to degradation, is
      proposed as the reaction of a nucleophilic adduct, Fe(II)OOH, which could
      directly react with the electron deficient triazine ring. It is highlighted that
      such degradation reactions must be explored for the complete degradation of the
      byproducts of the oxidative decomposition of atrazine.

PMID- 17008006
TI  - Electrochemical treatment of Procion Black 5B using cylindrical flow reactor--a
      pilot plant study.
AB  - The paper presents the results of an efficient electrochemical treatment of
      Procion Black 5B--a pilot plant study. Experiments were conducted at different
      current densities and selected electrolyte medium using Ti/RuO2 as anode,
      stainless-steel as cathode in a cylindrical flow reactor. By cyclic voltammetric
      analysis, the best condition for maximum redox reaction rate was found to be in
      NaCl medium. During the various stages of electrolysis, parameters such as COD,
      colour, FTIR, UV-vis spectra studies, energy consumption and mass transfer
      coefficient were computed and presented. The experimental results showed that the
      electrochemical oxidation process could effectively remove colour and the
      chemical oxygen demand (COD) from the synthetic dye effluent. The maximum COD
      reduction and colour removal efficiencies were 74.05% and 100%, respectively.
      Probable theory, reaction mechanism and modeling were proposed for the oxidation
      of dye effluent. The results obtained reveal the feasibilities of application of
      electrochemical treatment for the degradation of Procion Black 5B.

PMID- 17008007
TI  - Kinetic and wet oxidation of phenol catalyzed by non-promoted and potassium
      promoted manganese/cerium oxide.
AB  - The wet oxidation of organic compounds to CO2 and H2O has been shown to be a very
      efficient technique in the outflows treatment. This work focuses on the
      interaction of the chemical element potassium with the catalyst MnO2-CeO2 in the
      wet degradation of phenol. The reaction has been carried out in an autoclave with
      a controlled system of agitation, pressure, temperature and sampling of the
      liquid phase. The experiments were performed in the presence of the catalysts
      MnO2-CeO2 and K-MnO2-CeO2 in the following operational conditions: temperature of
      130 degrees C, P = 20.4 atm, catalyst concentration in the range 1.5-5.0 g/L,
      initial phenol concentration of 0.5 g/L, initial pH varying between 6.8 and 8.5,
      and percentage of potassium in the catalyst MnO2-CeO2 ranging between 0% and 10%.
      Curves indicating the profile of conversion of total organic carbon show that the
      phenol degradation is favored when the potassium quantity is reduced. This
      behaviour is confirmed by BET analysis, whereby the catalyst presents larger
      specific area when compared to the percentages of other components. Regardless of
      the catalyst used in the phenol oxidation, the kinetic constant of reaction had
      the same order of magnitude for two parallel stages proposed by a first-order
      kinetic model.

PMID- 17008008
TI  - A novel thermostable alpha-galactosidase from the thermophilic fungus Thermomyces
      lanuginosus CBS 395.62/b: purification and characterization.
AB  - High levels of an extracellular alpha-galactosidase are produced by the
      thermophilic fungus Thermomyces lanuginosus CBS 395.62/b when grown in submerse
      culture and induced by sucrose. The enzyme was purified 114-fold from the culture
      supernatant by (NH(4))(2)SO(4) fractionation, and by chromatographical steps
      including Sepharose CL-6B gel filtration, DEAE-Sepharose FF anion-exchange, Q
      Sepharose FF anion-exchange and Superose 12 gel filtration. The purified enzyme
      exhibits apparent homogeneity as judged by sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis (SDS-PAGE) and iso-electric focusing (IEF). The native
      molecular weight of the monomeric alpha-galactosidase is 93 kDa with an
      isoelectric point of 3.9. The enzyme displays a pH and temperature optimum of 5
      5.5 and 65 degrees C, respectively. The purified enzyme retains more than 90% of
      its activity at 45 degrees C in a pH range from 5.5 to 9.0. The enzyme proves to
      be a glycoprotein and its carbohydrate content is 5.3%. Kinetic parameters were
      determined for the substrates p-nitrophenyl-alpha-galactopyranoside, raffinose
      and stachyose and very similar K(m) values of 1.13 mM, 1.61 mM and 1.17 mM were
      found. Mn(++) ions activates enzyme activity, whereas inhibitory effects can be
      observed with Ca(++), Zn(++) and Hg(++). Five min incubation at 65 degrees with
      10 mM Ag(+) results in complete inactivation of the purified alpha-galactosidase.
      Amino acid sequence alignment of N-terminal sequence data allows the alpha
      galactosidase from Thermomyces lanuginosus to be classified in glycosyl hydrolase
      family 36.

PMID- 17008009
TI  - Selective binding of imatinib to the genetic variants of human alpha1-acid
      glycoprotein.
AB  - Imatinib is a selective tyrosine kinase inhibitor, successfully used for the
      treatment of chronic myelogenous leukaemia. Its strong plasma protein binding
      referred to alpha1-acid glycoprotein (AGP) component was found to inhibit the
      pharmacological activity. AGP shows genetic polymorphism and the two main genetic
      variants have different drug binding properties. The binding characteristics of
      imatinib to AGP genetic variants and the possibility of its binding interactions
      were investigated by various methods. The results proved that binding of imatinib
      to the two main genetic variants is very different, the high affinity binding
      belongs dominantly to the F1-S variant. This interaction is accompanied with
      specific spectral changes (induced circular dichroism, UV change, intrinsic
      fluorescence quenching), suggesting that the bound ligand has chiral conformation
      that would largely overlap with other ligands inside the protein cavity. Binding
      parameters of Ka=1.7(+/-0.2)x10(6)M(-1) and n=0.94 could be determined for the
      binding on the F1-S variant at 37 degrees . Imatinib binding on the A variant is
      weaker and less specific. The binding affinity of imatinib to human serum albumin
      (nKa approximately 3 x 10(4)M(-1)) is low. Pharmacologically relevant binding
      interactions with other drugs can be expected on the F1-S variant of AGP.

PMID- 17008010
TI  - Dual benefit procedures: combining aesthetic surgery with burn reconstruction.
AB  - Burn accounts for a significant proportion of injuries, and of these, the face,
      neck, and anterior torso are commonly affected. Burn scars remain a lasting
      reminder of the insult both for the patient and the outside world. There is
      little doubt that the changes in appearance, and limitations imposed by the burn
      scar contribute to a negative body image. We present a series of four women, who
      sustained full thickness burns in childhood with subsequent burn scarring and
      contracture. These women were noted to have poor body image in areas less
      affected by burn injury, notably breast ptosis, breast asymmetry and abdominal
      skin laxity. They were suitable candidates for planned aesthetic procedures, and
      the skin excised was used to effect synchronous burn reconstruction or
      contracture release. We believe the potential to use areas of skin excised during
      aesthetic procedures as possible donor sites of full thickness skin, confers the
      dual benefits of improved aesthetic and functional outcome, while minimising
      unnecessary donor site morbidity.

PMID- 17008011
TI  - Evidence profiles for lung cancer: benefit/harms data based on the totality of
      randomized evidence.

PMID- 17008012
TI  - Clinical review - small cell carcinoma of the bladder.
AB  - OBJECTIVES: To review the published literature on the diagnosis and management of
      small cell carcinoma of the bladder (SCCB). METHODS: Papers were identified by
      searches of PubMed using the terms "small cell", "bladder" and "carcinoma".
      Additional papers were identified from review of references of relevant articles.
      RESULTS: SCCB comprises less than 1% of bladder malignancies. It is an aggressive
      tumour that commonly presents at an advanced stage, in an elderly population.
      Consequently, patients are often not fit for anti-neoplastic therapy. In fit
      patients, the bedrock of treatment in the majority of cases is platinum-based
      systemic chemotherapy, which was the only factor predictive of improved outcome
      on multivariate analysis in one large review. The use of neoadjuvant chemotherapy
      has been associated with favourable results and may therefore be the preferred
      approach when scheduling treatment. Options for local management comprise surgery
      or radiotherapy (sequentially or concurrently with chemotherapy), both of which
      are potentially curative in selected cases. However, the subsequent frequent
      development of urothelial malignancies with bladder-sparing approaches should be
      considered when planning treatment, particularly in younger patients. Prognosis
      of SCCB overall is poor, the median survival of all cases varies from 4 to 23
      months, and overall survival at 5 years from 10% to 40% of patients. CONCLUSIONS:
      SCCB is a rare and aggressive tumour with a poor prognosis. Future efforts should
      be directed at its early detection and the development of more effective systemic
      therapies.

PMID- 17008013
TI  - Safety of adjuvant aromatase inhibitor therapy.
AB  - The long-term effects of aromatase inhibitors (AIs) on lipids and bone and
      cardiovascular and gynecological health are of particular interest to clinicians.
      The safety data of anastrozole, letrozole, and exemestane are limited to trials
      with follow-up periods of 5 years or less, and much of the data arise from
      comparisons with tamoxifen, a drug that has both estrogen agonist and antagonist
      effects. With the lack of extensive long-term data, indirect comparisons between
      the safety profiles of the AIs provide some insights. Although results from these
      indirect comparisons should be interpreted cautiously, they may assist physicians
      in the decision-making process. Thus far, AIs confer an increased risk of bone
      loss and osteoporosis and fractures, while the effects on lipid profiles and
      cardiovascular health seem to indicate only that AIs lack the cardioprotective
      and lipid-lowering effects of tamoxifen. Some data also are available from
      comparisons with placebo, a more appropriate comparator to investigate the
      tolerability and safety of a specific drug. In the MA.17 trial, patients
      receiving letrozole experienced similar rates of cardiovascular ischemic events
      and hypercholesterolemia compared with those on placebo. The significant clinical
      benefits of AIs compared with tamoxifen have been achieved without worsening
      quality of life.

PMID- 17008014
TI  - Targeted therapies in melanoma.
AB  - In the last decade the incidence of melanoma has been rising. Despite this,
      survival remains substantially constant because early diagnosis of thin lesions
      has increased. By contrast, metastatic melanoma continues to have a poor
      prognosis and it still represents a challenge for oncologists. Response rates
      with single agent dacarbazine range from 10% to 25% with median survival of 8
      months. The advent of new drugs with specific mechanisms of action could help to
      improve the poor results of traditional therapies. In this review, we focused on
      the novel agents that entered clinical trials in melanoma patients. We show the
      results of some clinical trials with target-oriented drugs in melanoma patients.
      Moreover pre-clinical data and rationale for use in melanoma was explained.
      Trials with protein-kinase inhibitors, anti-CTLA-4 agents, pro-apoptotic
      oligonucleotides and anti-angiogenic agents were reviewed. Combinations with
      chemotherapeutic agents, immunotherapy and vaccine therapy were also analyzed.

PMID- 17008015
TI  - The up-to-date evidence on colposcopy practice and treatment of cervical
      intraepithelial neoplasia: the Cochrane colposcopy & cervical cytopathology
      collaborative group (C5 group) approach.
AB  - This overview presents the up-to-date evidence on colposcopy practice and other
      diagnostic modalities such as HPV DNA test and cytology for cervical
      intraepithelial neoplasia (CIN). Current evidence supports the use of colposcopy
      for the detection of intraepithelial lesions as a second line tool. CIN treatment
      involves either excisional or destructive techniques, usually performed under
      local anesthesia. Although a debate exists about the most efficient approach, the
      currently available evidence reveals no differences in efficacy among the
      available conservative methods of treatment. New evidence supports treatment by
      destructive rather than excisional techniques, at least for low grade lesions in
      women wishing future childbearing, as they appear to have no apparent pregnancy
      related morbidity. Treatment failures rates might increase in cases of involved
      excision margins, older age or glandular involvement. There is no worldwide
      consensus on the optimal follow-up policy, interventions or frequency in
      surveillance after treatment. HPV DNA test combined with either colposcopy or
      cytology is a promising combination for the early detection of treatment failures
      due to residual disease. Existing guidelines should probably be updated
      incorporating the new information emerged from recently published work.

PMID- 17008016
TI  - Divergent anatomical pattern of D1 and D3 binding and dopamine- and cyclic AMP
      regulated phosphoprotein of 32 kDa mRNA expression in the Roman rat strains:
      Implications for drug addiction.
AB  - Autoradiography analysis of D1, D2 and D3 dopamine receptors and in situ
      hybridization analysis of mRNA for dopamine and cAMP regulated phosphoprotein of
      32 kDa (DARPP-32) were performed in brains of naive Roman high avoidance (RHA)
      and Roman low avoidance (RLA) inbred rats. These strains, genetically selected
      for high (RHA) or extremely low (RLA) active avoidance acquisition in the two-way
      shuttle box, differ in indices of dopaminergic activity along with
      sensation/novelty and substance-seeking behavioral profiles. The present study
      shows no differences in D2 receptor binding between the two strains. In contrast,
      the D1 and D3 receptor binding in the nucleus accumbens was higher in RHA-I rats,
      whereas RLA-I rats show higher D3 binding in the Calleja islands. Together with
      previous evidence showing behavioral and presynaptic differences related to the
      dopamine system, the present results suggest a higher dopaminergic tone at the
      nucleus accumbens shell in RHA-I rats. Besides, the comparison of the expression
      pattern of DARPP-32 mRNA with that of dopamine receptor binding revealed a
      mismatch in some amygdala nuclei. In some cortical structures (prelimbic and
      cingulate cortices, the dentate gyrus) as well as in the central amygdala, RHA-I
      rats showed higher DARPP-32 mRNA expression than RLA-I rats. Hence, RHA-I and RLA
      I rats may be a useful tool to identify dopamine-related mechanisms that
      predispose to drug and alcohol dependence.

PMID- 17008017
TI  - Substantia nigra compacta neurons that innervate the reticular thalamic nucleus
      in the rat also project to striatum or globus pallidus: implications for abnormal
      motor behavior.
AB  - The projections of the substantia nigra pars compacta (SNc) to the reticular
      thalamic nucleus (RTn) were assessed by measuring dopamine content and counting
      tyrosine hydroxylase positive (TH (+)) cells in rats with unilateral lesions
      induced by 6-hydroxydopamine (6-OHDA), and by using a fluorescent tract-tracing
      technique in rats without lesions. Injection of 6-OHDA in the RTn reduced
      dopamine content and the number of TH (+) cells in the SNc by about 50%.
      Branching of SNc was suggested by the finding that 6-OHDA deposited in the RTn
      significantly reduced dopamine in the striatum and globus pallidus. Moreover,
      injections of 6-OHDA into either the striatum or the globus pallidus
      significantly reduced dopamine content in the RTn. Fluorescent tracers injected
      into the RTn labeled TH (+) cells in the SNc. A high proportion of these TH (+)
      cells was double labeled when tracers were also injected into either the globus
      pallidus or striatum. Other experiments showed that systemic injection of
      apomorphine or methamphetamine induced turning behavior in rats with local
      deposits of 6-OHDA in either the RTn or the studied basal ganglia nuclei. The
      extensive dopaminergic branching suggests that the abnormal motor behavior of
      rats with 6-OHDA deposits in the RTn may be caused by dopaminergic denervation of
      more than one structure. The fact that lesion of a single dopaminergic neuron can
      reduce dopamine transmission in more than one structure is probably important in
      generating the manifestations of Parkinson's disease.

PMID- 17008018
TI  - Organizational and activational effects of testosterone on carrageenan-induced
      inflammatory pain and morphine analgesia.
AB  - Men are typically reported to have higher pain thresholds than women. Gonadal
      hormones, particularly testosterone for males, may contribute to this effect.
      This study tested whether changes in the male hormonal milieu early or late in
      development alter the inflammatory pain induced by carrageenan (CARR, 3%,
      intraarticular). Male rats were either gonadectomized or sham gonadectomized
      neonatally. Once adults, the same rats underwent either sham surgery or
      gonadectomy, and received a testosterone or oil implant. After baseline testing
      two weeks later, animals were tested in response to mechanical and thermal
      stimulation following CARR-induced inflammation and injection of saline, 1 mg/kg,
      or 5 mg/kg morphine. Hormone alterations did not affect baseline responses, but
      CARR induced mechanical and thermal hyperalgesia in the injured limb. Gonadectomy
      in adult males injected with saline enhanced inflammation-induced sensitivity to
      mechanical but not thermal stimulation and the effect was reversed by
      testosterone. After inflammation, saline-treated males gonadectomized neonatally
      displayed lower mechanical threshold than control sham animals but this effect
      was not reversed by testosterone. Both doses of morphine increased mechanical and
      thermal thresholds. However, compared with the control group, 1 mg/kg morphine
      was equally effective in reducing mechanical hyperalgesia among groups of animals
      gonadectomized as adults, but less effective in males gonadectomized neonatally.
      The results suggest that in males: 1. the antihyperalgesic effect of testosterone
      (or its metabolites) in CARR-induced inflammation is established during
      development and maintained by circulating levels of testosterone in adulthood; 2.
      the nociception-related interaction between the opioid and gonadal systems
      influences the sensitivity to mechanical stimuli and is likely established during
      the period of sexual differentiation.

PMID- 17008020
TI  - Developmental localization of potassium chloride co-transporter 2 in granule
      cells of the early postnatal mouse cerebellum with special reference to the
      synapse formation.
AB  - In the adult CNS, GABA is the predominant inhibitory neurotransmitter, mediating
      the hyperpolarization of membrane potential and regulating the glutamatergic
      activity. In the immature CNS, on the other hand, GABA mediates depolarization
      and is involved in controlling morphogenesis. This developmental shift in GABA
      actions from depolarization to hyperpolarization occurs as a result of decreasing
      the intracellular chloride ion (Cl(-)) concentration ([Cl(-)](i)) which is
      regulated by the potassium (K(+))-Cl(-) co-transporter 2 (KCC2). To clarify the
      time-course of changes in the GABA actions during development, we examined the
      developmental localization of the KCC2 in the granule cells of the postnatal
      mouse cerebellum using specific antibodies against KCC2. The granule cell
      precursors and migrating granule cells were devoid of immunoreactivity against
      KCC2 antibodies. At postnatal day 3 (P3), the KCC2-immunolabeling was negative in
      the internal granular layer, although synaptophysin-positive mossy fiber
      terminals were detected. At P5, we first detected the KCC2-immunolabeling at the
      somata of granule cells and their dendrites before granule cells received
      inhibitory input from Golgi cells. Almost all KCC2-positive dendrites (more than
      98%) attached to and formed synapses with mossy fiber terminals. As development
      proceeded, the number of KCC2-positive granule cells increased, and all granule
      cells became positive by P21. These results suggested that GABAergic transmission
      on granule cells might shift from excitation to inhibition after the synapse
      formation, and the excitatory synapse-formation and related factors might be the
      triggers for the expression and localization of the KCC2 in the granule cells.
      Furthermore, it was also suggested that formation of the GABAergic synapses and
      GABAergic transmission were not necessary for the KCC2-expression in the mouse
      cerebellar granule cells in vivo.

PMID- 17008019
TI  - Electrophysiological characterization of neurons in the dorsolateral pontine
      rapid-eye-movement sleep induction zone of the rat: Intrinsic membrane properties
      and responses to carbachol and orexins.
AB  - Pharmacological, lesion and single-unit recording techniques in several animal
      species have identified a region of the pontine reticular formation
      (subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved
      in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic
      membrane properties and responses of SubC neurons to neurotransmitters important
      in REM sleep control, such as acetylcholine and orexins/hypocretins, have not
      previously been examined in any animal species and thus were targeted in this
      study. We obtained whole-cell patch-clamp recordings from visually identified
      SubC neurons in rat brain slices in vitro. Two groups of large neurons (mean
      diameter 30 and 27 mum) were tentatively identified as cholinergic (rostral SubC)
      and noradrenergic (caudal SubC) neurons. SubC reticular neurons (non-cholinergic,
      non-noradrenergic) showed a medium-sized depolarizing sag during hyperpolarizing
      current pulses and often had a rebound depolarization (low-threshold spike, LTS).
      During depolarizing current pulses they exhibited little adaptation and fired
      maximally at 30-90 Hz. Those SubC reticular neurons excited by carbachol (n=27)
      fired spontaneously at 6 Hz, often exhibited a moderately sized LTS, and varied
      widely in size (17-42 mum). Carbachol-inhibited SubC reticular neurons were
      medium-sized (15-25 mum) and constituted two groups. The larger group (n=22) was
      silent at rest and possessed a prominent LTS and associated one to four action
      potentials. The second, smaller group (n=8) had a delayed return to baseline at
      the offset of hyperpolarizing pulses. Orexins excited both carbachol excited and
      carbachol inhibited SubC reticular neurons. SubC reticular neurons had intrinsic
      membrane properties and responses to carbachol similar to those described for
      other reticular neurons but a larger number of carbachol inhibited neurons were
      found (>50%), the majority of which demonstrated a prominent LTS and may
      correspond to pontine-geniculate-occipital burst neurons. Some or all carbachol
      excited neurons are presumably REM-on neurons.

PMID- 17008021
TI  - The involvement of cholinergic and noradrenergic systems in behavioral recovery
      following oxotremorine treatment to chronically stressed rats.
AB  - Chronic stress in rats has been shown to impair learning and memory, and
      precipitate several affective disorders like depression and anxiety. The
      mechanisms involved in these stress-induced disorders and the possible reversal
      are poorly understood, thus limiting the number of drugs available for their
      treatment. Our earlier studies suggest cholinergic dysfunction as the underlying
      cause in the behavioral deficits following stress. Muscarinic cholinergic
      agonist, oxotremorine is demonstrated to have a beneficial effect in reversing
      brain injury-induced behavioral dysfunction. In this study, we have evaluated the
      effect of oxotremorine treatment on chronic restraint stress-induced cognitive
      deficits. Rats were subjected to restraint stress (6 h/day) for 21 days followed
      by oxotremorine treatment for 10 days. Spatial learning and memory was assessed
      in a partially baited eight-arm radial maze task. Stressed rats exhibited
      impairment in performance, with decreased percentage of correct choices and an
      increase in the number of reference memory errors (RMEs). Oxotremorine treatment
      (0.1 or 0.2 mg/kg, i.p.) to stressed rats resulted in a significant increase in
      the percent correct choices and a decrease in the number of RMEs compared with
      stress as well as the stress+vehicle-treated groups. In the retention test,
      oxotremorine treated rats committed less RMEs compared with the stress group.
      Chronic restraint stress decreased acetylcholinesterase (AChE) activity in the
      hippocampus, frontal cortex and septum, which was reversed by both the doses of
      oxotremorine. Further, oxotremorine treatment also restored the norepinephrine
      levels in the hippocampus and frontal cortex. Thus, this study demonstrates the
      potential of cholinergic muscarinic agonists and the involvement of both
      cholinergic and noradrenergic systems in the reversal of stress-induced learning
      and memory deficits.

PMID- 17008023
TI  - Neurotrophic receptor TrkB: Is it a predictor of poor prognosis for carcinoma
      patients?
AB  - The neurotrophic receptor tyrosine kinase TrkB, while binding its high affinity
      ligand brain-derived neurotrophic factor (BDNF), will play an essential role for
      nervous system development, neuronal survival, differentiation, and maintenance.
      However, accumulating evidences implies that TrkB signal pathway may also be
      involved in a variety of human cancers, in which TrkB is likely to play a role in
      initiation and metastasis of carcinomas. Overexpression of TrkB is often
      correlated with the tumorigenesis, angiogenesis and drug resistance in these
      malignancies, contributing significantly to the metastasis and aggressive
      phenotype of these poor prognosis tumors. The evidences to show the significant
      contribution of TrkB to malignancy not only came from solid tumors such as
      neoblastoma, pancreas cancer, Wilm's tumor and hepatocarcinoma, but also came
      from haematological malignancies such as Hodgkin lymphoma and multiple myeloma.
      In summary, besides its role in development and function of nervous system, TrkB
      is likely to also play a role in initiation and metastasis of carcinoma although
      it still remains to be further investigated and confirmed. Emerging data have
      suggested that TrkB may be a mediator as well as a marker of carcinogenesis and
      metastasis, therefore TrkB may be used as a valuable target for cancer therapy
      especially for the metastatic tumors with poor prognosis.

PMID- 17008022
TI  - High sensitivity analysis of amyloid-beta peptide composition in amyloid deposits
      from human and PS2APP mouse brain.
AB  - Cortical amyloid-beta (Abeta) deposition is considered essential in Alzheimer's
      disease (AD) and is also detectable in nondemented individuals with pathologic
      aging (PA). The present work presents a detailed analysis of the Abeta
      composition in various plaque types from human AD and PA cases, compared with
      plaque Abeta isolated from PS2APP mice. To determine minute amounts of Abeta from
      30 to 50 laser-dissected amyloid deposits, we used a highly sensitive mass
      spectrometry procedure after restriction protease lysyl endopeptidase (Lys-C)
      digestion. This approach allowed the analysis of the amino-terminus and,
      including a novel ionization modifier, for the first time the carboxy-terminus of
      Abeta at a detection limit of approximately 200 fmol. In addition, full length
      Abeta 40/42 and pyroglutamate 3-42 were analyzed using a highly sensitive urea
      based Western blot procedure. Generally, Abeta fragments were less accessible in
      human deposits, indicative of more posttranslational modifications. Thioflavine S
      positive cored plaques in AD were found to contain predominantly Abeta 42,
      whereas thioflavine S positive compact plaques and vascular amyloid consist
      mostly of Abeta 40. Diffuse plaques from AD and PA, as well as from PS2APP mice
      are composed predominantly of Abeta 1-42. Despite biochemical similarities in
      human and PS2APP mice, immuno-electron microscopy revealed an extensive
      extracellular matrix associated with Abeta fibrils in AD, specifically in diffuse
      plaques. Amino-terminal truncations of Abeta, especially pyroglutamate 3-40/42,
      are more frequently found in human plaques. In cored plaques we measured an
      increase of N-terminal truncations of approximately 20% between Braak stages IV
      to VI. In contrast, diffuse plaques of AD and PA cases, show consistently only
      low levels of amino-terminal truncations. Our data support the concept that
      diffuse plaques represent initial Abeta deposits but indicate a structural
      difference for Abeta depositions in human AD compared with PS2APP mice already at
      the stage of diffuse plaque formation.

PMID- 17008024
TI  - Phentermine, sibutramine and metformin could be used for the prevention and
      treatment of steroid-induced weight gain.

PMID- 17008025
TI  - A connection between medication adherence, patient sense of uniqueness, and the
      personalization of information.
AB  - Adherence to treatment regimens is important to achieve optimal disease
      management. However, nonadherence is evident across numerous clinical contexts,
      which leads to a higher disease burden on society. Among the various factors
      associated with patient adherence behavior, patient beliefs are the most
      influential set of factors. Several cognitive-social models and constructs that
      incorporate patient belief have been developed to explain patient health
      behaviors, such as the Health Belief Model, Self-Efficacy Model, Theory of
      Planned Behavior and so on. However, these models do not explain the formulation
      of health beliefs. The underlying mechanism accounting for patient variation in
      information processing that generates beliefs needs to be investigated, which
      will inform the development of interventions. We propose that patient's sense of
      uniqueness moderates the self-attribution of statistically-based information.
      Self-attribution is defined as a person's perceived probability that a statement
      applies to herself, and is influenced by experience and sense of uniqueness.
      Sense of uniqueness is a person's general belief regarding how unique she is.
      Statistically-based information is defined as information derived from or
      regarding aggregated effects or influences. Basically, the proposed hypothesis is
      that patients who have a stronger belief that they are unique are less likely to
      attribute to themselves statistically-based propositions regarding the majority
      of their group and are more likely to attribute to themselves statistically-based
      propositions regarding the minority. We further model the relationship between
      sense of uniqueness and self-attribution of information in terms of an idealized
      inexperienced person, and then extend the model to include the effect of personal
      experience. The estimation of hypothesis-specific effect parameters can be
      achieved by maximum likelihood. In conclusion, the sense of uniqueness hypothesis
      is general to the formulation of personal beliefs and consequently has
      implications for deliberate health behavior and indeed personal behavior in
      general.

PMID- 17008026
TI  - Losing weight by defaecating at night theory: The gastroenterologists'
      perspective.

PMID- 17008027
TI  - Hair zinc, aflatoxin and malnutrition.

PMID- 17008028
TI  - The possible role of protein X, a putative auxiliary factor in pathological prion
      replication, in regulating a physiological endoproteolytic cleavage of cellular
      prion protein.
AB  - The posttranslational conformational conversion of the cellular isoform of prion
      protein PrP(C) into its scrapie isoform PrP(Sc) is the fundamental process
      underlying the pathogenesis of prion disease. Based on several transgenic data,
      it has been postulated that a putative auxiliary factor denoted protein X
      functions as a molecular chaperone through its unfolding activity of PrP(C)
      during the formation of PrP(Sc). However, the assumption that protein X therefore
      exists exclusively in prion diseases appears improbable and thus, it should have
      some simultaneous physiological role. We, hereby, propose a novel concept - a
      characteristic role of protein X in supporting a physiological endoproteolytic
      cleavage of PrP(C). The events corresponding to the formation of the
      physiologically metabolized PrP(C) or the pathologically transformed PrP(Sc) are
      mutually exclusive. Amino acid residues that are critical in terms of the target
      site of protein X for the pathological alteration into PrP(Sc) overlap at the
      cleavage site. These amino acid residues tend to have a hydrophobic property and
      are most probably found buried inside the native protein structure. Therefore, a
      putative molecular chaperone identical to protein X may target the same
      hydrophobic residues in PrP(C) and work in conjunction with either PrP(Sc) in
      prion disease or PrP proteases during the physiological state. This postulation
      may help explain in a relatively simple manner these two mutually exclusive
      phenomena, viz. the physiological endoproteolytic cleavage of PrP(C) and its
      pathological conversion into PrP(Sc).

PMID- 17008029
TI  - Changes in PTSD symptomatology during acute and protracted alcohol and cocaine
      abstinence.
AB  - Previous research with substance users has demonstrated, across a variety of
      psychiatric disorders, significant decreases in psychological symptoms during
      early substance abstinence. To build on this literature, the current study
      prospectively assessed trauma symptomatology over 28 days during acute and
      protracted cocaine and alcohol abstinence. Participants were 162 male and female
      cocaine and/or alcohol dependent outpatients who reported a history of trauma.
      Trauma-related symptoms and substance use were assessed at 2, 5, 10, 14, 21, and
      28 days following last substance use. For participants who were known to relapse,
      assessments began again after the last day of substance use. Latent growth
      modeling was employed to estimate changes in posttraumatic stress disorder (PTSD)
      symptoms. Consistent with studies of other psychiatric syndromes, PTSD symptoms
      declined across the 28-day study period regardless of withdrawal substance (i.e.,
      cocaine or alcohol). The majority of change in trauma symptoms occurred within 2
      weeks of last substance use. Moreover, while trauma symptoms for the PTSD
      participants were more severe than those reported by the non-PTSD participants,
      trauma symptoms declined across the study period at the same rate irrespective of
      PTSD status.

PMID- 17008031
TI  - Diversity and evolution of Ty1-copia and Ty3-gypsy retroelements in the non
      photosynthetic flowering plants Orobanche and Phelipanche (Orobanchaceae).
AB  - We present the first study on the diversity and evolution of Ty1-copia and Ty3
      gypsy retroelements in a group of non-photosynthetic flowering plants. To this
      end partial sequences of the reverse transcriptase (rt) gene were obtained from
      20 clones for each retroelement type from seven and six accessions of Orobanche
      and Phelipanche (Orobanchaceae), respectively. Overall sequence similarity is
      higher in Ty3-gypsy elements than in Ty1-copia elements in agreement with the
      results from other angiosperm groups. Higher sequence diversity and stronger
      phylogenetic structure, especially of Ty1-copia sequences, in Orobanche species
      compared to Phelipanche species support the previously suggested hypothesis
      (based on karyological and cytological data) that genomes of Orobanche species
      are more dynamic than those of Phelipanche species. No evidence was found for
      intraspecific differences of retroelement diversity nor for differences between
      pest taxa and their putative wild relatives, e.g., O. crenata and O. owerini. The
      occurrence of a few sequences from Phelipanche species in clades otherwise
      comprising sequences from Orobanche species might be due to horizontal gene
      transfer, but the alternative of vertical transmission cannot be rejected
      unambiguously.

PMID- 17008030
TI  - Oral fluid as an alternative matrix to monitor opiate and cocaine use in
      substance-abuse treatment patients.
AB  - Interest in oral fluid as an alternative matrix for monitoring drug use is due to
      its ease-of-collection and non-invasiveness; however, limited data are available
      on the disposition of drugs into oral fluid. The objective of this research was
      to provide data on the presence and concentrations of heroin, cocaine and
      multiple metabolites in oral fluid after illicit opioid and cocaine use. Thrice
      weekly oral fluid specimens (N=403) from 16 pregnant opiate-dependent women were
      obtained with the Salivette oral fluid collection device. Evidence of heroin
      (N=62) and cocaine (N=130) use was detected in oral fluid by LC-APCI-MS/MS. 6
      Acetylmorphine (6-AM), heroin and morphine were the major opiates detected, with
      median concentrations of 5.2, 2.3, and 7.5 microg/L, respectively. Cocaine and
      benzoylecgonine (BE) had median concentrations of 6.4 and 3.4 microg/L.
      Application of the Substance Abuse Mental Health Services Administration (SAMHSA)
      recommended cutoffs for morphine and codeine (40 microg/L), 6-AM (4 microg/L) and
      cocaine and BE (8 microg/L), yielded 28 opiate- and 50 cocaine-positive
      specimens. Oral fluid is a promising alternative matrix to monitor opiate and
      cocaine use in drug testing programs. These data guide interpretation of oral
      fluid test results and evaluate currently proposed SAMHSA oral fluid testing
      cutoffs.

PMID- 17008032
TI  - Genes from a Dietzia sp. for synthesis of C40 and C50 beta-cyclic carotenoids.
AB  - Dietzia sp. CQ4 accumulated the C(40) beta-cyclic carotenoids (canthaxanthin and
      echinenone) and the C(50) beta-cyclic carotenoid (C.p.450 monoglucoside). A plant
      type lycopene beta-cyclase gene crtL was identified for beta-cyclization of the
      C(40) carotenoids. A carotenoid synthesis gene cluster was identified away from
      the crtL gene, which contained the crtEBI genes for the synthesis of lycopene
      followed by the lbtABC genes for lycopene elongation and beta-cyclization of the
      C(50) carotenoids. This C(50) beta-cyclic carotenoid synthesis gene cluster from
      Dietzia sp. CQ4 showed high homology with the gene clusters for synthesizing the
      C(50) epsilon-cyclic carotenoids (decaprenoxanthin and glucosides) from
      Corynebacterium glutamicum and Agromyces mediolanus. One unique feature of the
      C(50) beta-cyclic carotenoid synthesis genes in Dietzia sp. CQ4 was that the gene
      encoding a C(50) carotenoid beta-cyclase subunit and the gene encoding the
      lycopene elongase appeared to be fused as a single gene (lbtBC). Expression of
      the gene (lbtA) encoding another subunit of the C(50) carotenoid beta-cyclase and
      the lbtBC gene in lycopene-accumulating Escherichia coli produced almost
      exclusively the C(50) beta-cyclic carotenoid C.p.450. One gene (crtX) with high
      homology to glycosyl transferases was transcribed in the opposite orientation
      downstream of the lbtBC gene. The crtX gene was likely involved in C.p.450
      glucosylation in Dietzia sp. CQ4. The pathway analogous to the synthesis of the
      C(50) epsilon-cyclic carotenoids was proposed for the synthesis of the C(50) beta
      cyclic carotenoids.

PMID- 17008034
TI  - Encapsulation of hydrophobic drugs in polymeric micelles through co-solvent
      evaporation: the effect of solvent composition on micellar properties and drug
      loading.
AB  - This study was designed to develop an optimized co-solvent evaporation procedure
      for the efficient encapsulation of hydrophobic drugs in polymeric micelles of
      methoxy poly(ethylene oxide)-block-poly(epsilon-caprolactone) (MePEO-b-PCL).
      MePEO-b-PCL block copolymers having varied MePEO and PCL molecular weights were
      synthesized, assembled to polymeric micelles, and used for the encapsulation of
      cyclosporine A (CyA) by a co-solvent evaporation method. The co-solvent
      composition was varied by changing the type of organic co-solvent (using acetone,
      acetonitrile and tetrahydrofuran), the ratio of organic to aqueous phase, and
      their order of addition. Carrier size, morphology and encapsulated CyA levels
      were defined by dynamic light scattering (DLS), transmission electron microscopy
      (TEM) and HPLC, respectively, and the effect of co-solvent composition on
      micellar properties and loaded CyA levels was evaluated. Application of acetone
      and acetonitrile as the selective co-solvent for the core-forming block led to a
      decrease in the average diameter of self-assembled structures. When acetone was
      added to water, a decrease in the ratio of organic to aqueous phase led to an
      increase in the loading efficiency of CyA in MePEO-b-PCL micelles. A similar
      trend in CyA loading was observed for MePEO-b-PCL micelles of varied MePEO and
      PCL block lengths. The ratio of organic to aqueous phase did not affect CyA
      loading when water was added to acetone. Irrespective of the order of addition,
      the decrease in the organic to aqueous phase ratio caused a reduction in the
      average diameter of the empty and CyA loaded micelles. We conclude that the co
      solvent evaporation method may be optimized to improve the efficiency of drug
      encapsulation in polymeric micelles. For CyA encapsulation in MePEO-b-PCL
      micelles, addition of acetone to water at lower organic to aqueous phase ratio is
      shown to be the optimum procedure leading to higher drug encapsulation and
      smaller average diameter for the self-assembled structures.

PMID- 17008033
TI  - Prenatal mood disturbance predicts sleep problems in infancy and toddlerhood.
AB  - BACKGROUND: Experimental animal data link prenatal stress with sleep disturbance
      in offspring, but the link in humans is unclear. AIMS: To investigate the link
      between prenatal maternal anxiety and depression and infant sleep disturbance
      from 6 to 30 months of age. STUDY DESIGN: Longitudinal prospective study of a
      large birth cohort from pregnancy to 30 months. Questionnaire measures of anxiety
      and depression were completed by mothers at 18 and 32 weeks gestation and at 8
      weeks and 8 months postpartum. SUBJECTS: The ALSPAC cohort, a prospective
      community study of women in the UK who have been followed since pregnancy.
      OUTCOME MEASURES: Measures of total sleep time, number of awakenings, and broadly
      defined sleep problems were available on children at ages 6, 18, and 30 months.
      RESULTS: Reliable measures of total sleep time, nighttime awakenings, and sleep
      problems were identified at 6, 18, and 30 months. Higher levels of prenatal
      maternal anxiety and depression predicted more sleep problems at 18 and 30
      months, after controlling for postnatal mood and obstetric and psychosocial
      covariates; the association was not restricted to clinical extremes. No link with
      total sleep time was observed. CONCLUSIONS: Mood disturbance in pregnancy has
      persisting effects on sleep problems in the child, a finding that is consistent
      with experimental animal research. The findings add to a growing literature
      showing that maternal prenatal stress, anxiety, and depression may have lasting
      effects on child development.

PMID- 17008035
TI  - Novel solvent-free fabrication of biodegradable poly-lactic-glycolic acid (PLGA)
      capsules for antibiotics and rhBMP-2 delivery.
AB  - Osteomyelitis has been one of the most common causes of post-operative problems
      and complications despite the advances in surgical techniques and the
      availability of newly developed antibiotics. Local antibiotic and growth factor
      delivery devices for treatment of various surgical infections have been studied
      recently, especially in the case of orthopedic infections. The report was to
      develop novel solvent-free biodegradable capsules for antibiotics and growth
      factors delivery. To fabricate a biodegradable capsule, polylactide-polyglycolide
      copolymers were pre-mixed with vancomycin. The mixture was then compression
      molded and sintered to form a cylinder with a cover of 8 mm in diameter. After
      the addition of 1 and 10 microg recombinant bone morphogenetic protein (rhBMP-2)
      into the core, an ultrasonic welder was used to seal the capsules. An elution
      method was employed to characterize the in vitro release characteristics of the
      antibiotics and the rhBMP-2 over a 30-day period. The HPLC analysis and the
      bacterial inhibition test showed that biodegradable capsules released high
      concentrations and activity of vancomycin (well above the minimum inhibition
      concentration) in vitro for the period of time needed to treat bone infection;
      i.e. 4-6 weeks. In addition, the results of ELISA and ALP tests also suggested
      that the capsules released active rhBMP-2 for up to 30 days. By adopting this
      novel technique, we will be able to fabricate biodegradable capsules of various
      medicines for long-term drug deliveries.

PMID- 17008036
TI  - The approximate scaling law of the cochlea box model.
AB  - The hydrodynamic box-model of the cochlea is reconsidered here for the primary
      purpose of studying in detail the approximate scaling law that governs tonotopic
      responses in the frequency domain. "Scaling law" here means that any two
      solutions representing waveforms elicited by tones of equal amplitudes differ
      only by a complex factor depending on frequency. It is shown that this property
      holds with excellent approximation almost all along the basilar membrane (BM)
      length, with the exception of a small region adjacent to the BM base. The
      analytical expression of the approximate law is explicitly given and compared to
      numerical solutions carried out on a virtually exact implementation of the model.
      It differs significantly from that derived by Sondhi in 1978, which suffers from
      an inaccuracy in the hyperbolic approximation of the exact Green's function.
      Since the cochleae of mammals do not exhibit the scaling properties of the box
      model, the subject presented here may appear to be just an academic exercise. The
      results of our study, however, are significant in that a more general scaling law
      should hold for real cochleae. To support this hypothesis, an argument related to
      the problem of cochlear amplifier-gain stabilization is advanced.

PMID- 17008037
TI  - Therapeutic efficacy of intra-cochlear administration of methylprednisolone after
      acoustic trauma caused by gunshot noise in guinea pigs.
AB  - The therapeutic efficacy of cochlear infusion of methylprednisolone (MP) after an
      impulse noise trauma (170dB SPL peak) was evaluated in guinea pigs. The compound
      action potential threshold shifts were measured over a 14 days recovery period
      after the gunshot exposure. For each animal, one of the cochlea was perfused
      directly into the scala tympani with MP during 7 days via a mini-osmotic pump,
      whereas the other cochlea was not pump-implanted. The functional study of hearing
      was supplemented by histological analysis. Forty eight hours after the trauma,
      significant differences between auditory threshold shifts in the implanted and
      non-implanted ears were observed for frequencies above 8kHz. At day 7, the
      difference was significant for only one frequency and no difference was observed
      after 14 days recovery. Cochleograms showed that the hair cell losses were
      significantly lower in the MP treated ears. This work indicates that direct
      infusion of MP into perilymphatic space accelerates hearing recovery, reduces
      hair cell losses after impulse noise trauma but does not limit permanent
      threshold shifts.

PMID- 17008038
TI  - Y chromosome STR haplotypes of Tibetan Living Tibet Lassa.
AB  - Allele frequencies and haplotypes of the 17 Y-chromosome STRs loci, namely DYS19,
      DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438,
      DYS439, DYS448, DYS456, DYS458, DYS635 (YGATA C4), and YGATA H4 were determined
      in a sample of 131 healthy unrelated males from the Lassa area of Tibet Autonomy
      Region of China (SW China). In 131 samples 106 different haplotypes were
      encountered, of which 105 were observed only once. The overall haplotype
      diversity was 0.9998. The results demonstrate that these loci will be very useful
      for human identification in forensic cases and paternity tests in the Lassa
      region.

PMID- 17008039
TI  - Extramedullary haematopoiesis in liver of sudden infant death cases.
AB  - AIMS: To determine the frequency of extramedullary haematopoiesis (EMH) in sudden
      infant death and control cases, and to provide descriptive data on extramedullary
      haematopoietic islands and diffuse cells. METHODS: The study was carried out in
      51 SIDS and 102 non-SIDS cases. Liver-tissue sections were stained with
      haematoxylin and eosin, and immunohistochemistry was done with streptavidin
      biotin-peroxidase complexes by Polyclonal Haemoglobin "A" antibody. The
      prevalence of data was estimated statistically by Pearson chi-square test,
      descriptive statistics, and Kruskal-Wallis test. RESULTS: The Pearson chi-square
      values (CI: 95%; OR: 0.071-0.49; p: 0.0474) show higher frequency of EMH islands
      in SIDS than in controls. The number of diffuse extramedullary haematopoetic
      cells was higher in SIDS cases compared to non-SIDS (p=0.017). CONCLUSIONS: EMH
      is a frequent finding in SIDS cases, and this may be a consequence of anaemia
      associated with intrauterine hypoxia, or infections.

PMID- 17008040
TI  - Lower brainstem dysfunction in an infant with persistent primitive trigeminal
      artery.
AB  - A 6-month-old boy with persistent primitive trigeminal artery (PPTA) presented
      with stridor, dysphagia, delayed motor development and postural neck and shoulder
      dystonia. Magnetic resonance imaging/angiography and ultrasonography revealed
      PPTA, with flow from the dilated basilar artery to the right internal carotid
      artery, lower brainstem compression by the dilated basilar artery, and cerebellar
      vermis hypoplasia. Evoked potentials showed lower pons and medulla oblongata
      functional disruption. These lesions may be related to vascular etiology in the
      lower brainstem or to congenital malformation syndrome involving infratentorial
      structures. The relationship of this condition to Mobius syndrome is discussed.

PMID- 17008041
TI  - Delayed neuropsychiatric syndrome in a child following carbon monoxide poisoning.
AB  - Here, we report the case of a five-year-old boy with carbonic monoxide (CO)
      poisoning. The patient initially recovered after the initiation of hyperbaric
      oxygen (HBO) therapy, but lethargy as well as visual and gait disturbances
      appeared two days later. Left hemiparesis and mood lability also subsequently
      appeared. Slow frontal activity was noted on electroencephalography, while fluid
      attenuation inversion recovery and diffusion-weighted magnetic resonance imaging
      (MRI) revealed high signal-intensity lesions in the hippocampus and deeper layers
      of the occipital and frontal cerebral cortex. The neurological symptoms subsided
      gradually during the 10-day course of HBO therapy, but the left-hand paresis and
      quadrantic hemianopsia persisted, in association with impaired attention, slow
      mental processing, and incontinence. Lesions in the globus pallidum were noted on
      follow-up MRI at 14 days, and cortical lesions became evident as linear, low
      signal-intensity areas on T1-weighted imaging 4 months after presentation.
      Delayed neuropsychiatric syndrome in CO poisoning is rare in childhood, although
      children should be carefully monitored after CO exposure. The finding of cortical
      laminar necrosis in this patient is quite atypical in CO poisoning, and suggests
      a broader and previously nonpredicted pathomechanism in this condition.

PMID- 17008042
TI  - Acute encephalitis with refractory, repetitive partial seizures: case reports of
      this unusual post-encephalitic epilepsy.
AB  - We report on three acute encephalitis patients with refractory, repetitive
      partial seizures (AERRPS). All three suffered acute febrile episodes associated
      with status epilepticus, which necessitated high-dose barbiturate therapy under
      artificial ventilation for several weeks. Electroencephalography (EEG) revealed a
      predominance of diffuse epileptiform discharges initially, subsequently
      developing into periodic bursts of these discharges. Reduction of the barbiturate
      dosage resulted in clinical and subclinical partial seizures appearing
      repetitively in clusters. Prolonged fever persisted for 2-3 months, even several
      weeks after normalization of cell counts in the cerebrospinal fluid. The EEG
      showed an improvement after resolution of this fever, and seizures became less
      frequent, although still intractable. Oral administration of high-dose
      barbiturate and benzodiazepines were partially effective during the acute phase,
      and a barbiturate dependency, lasting for years, was noted in one patient.
      Steroid administration was effective in stopping the febrile episodes in one
      patient, with concurrent improvement in seizure control. Magnetic resonance
      imaging showed enhancement of bitemporal cortical areas in one patient, and high
      signal intensity on T2 weighted image in the bilateral claustrum in another
      patient. Diffuse cortical atrophy appeared within two months after the onset of
      encephalitis in all patients. The evolution of the seizures and EEG findings
      suggested a high degree of cortical excitability in AERRPS. In this report, we
      propose a tentative therapeutic regimen for seizure control in this condition. We
      also hypothesize that a prolonged inflammatory process exists in the cerebral
      cortex with AERRPS, and may be pivotal in the epileptogenesis.

PMID- 17008043
TI  - Consequences of pilocarpine-induced recurrent seizures in neonatal rats.
AB  - Accumulated evidence have shown that a series of morphological alternations occur
      in patients with epilepsy and in different epileptic animal models. Given most of
      animal model studies have been focused on adulthood stage, the effect of
      recurrent seizures to immature brain in neonatal period has not been well
      established. This study was designed to observe the certain morphological changes
      following recurrent seizures occurred in the neonatal rats. For seizure
      induction, neonatal Wistar rats were intraperitoneally injected with pilocarpine
      on postnatal day 1 (P1), P4 and P7. Rat pups were grouped and sacrificed at 1d,
      7d, 14d and 42d after the last pilocarpine injection respectively.
      Bromodeoxyuridine (BrdU) was intraperitoneally administered 36h before the rats
      were sacrificed. BrdU single and double labeling with neuronal markers were used
      to analyze cell proliferation and differentiation. Nissl and Timm staining were
      performed to evaluate cell loss and mossy fiber sprouting. Rats with neonatal
      seizures had a significant reduction in the number of Bromodeoxyuridine-(BrdU)
      labeled cells in the dentate gyrus compared with the control groups when the
      animals were killed either 1 or 7 days after the third seizure (P<0.05) but there
      was no difference between two groups on P21. On the contrary, BrdU-labeled cells
      significantly increased in the experimental group compared with control group on
      P49 (P<0.05). The majority of the BrdU-labeled cells colocalized with neuronal
      marker-NF200 (Neurofilament-200). Nissl staining showed that there was no obvious
      neuronal loss after seizure induction over all different time points. Rats with
      the survival time of 42 days after neonatal seizures developed to increased mossy
      fiber sprouting in both the CA3 region and supragranular zone of the dentate
      gyrus compared with the control groups (P<0.05). Taken together, the present
      findings suggest that synaptic reorganization only occurs at the later time point
      following recurrent seizures in neonatal rats, and neonatal recurrent seizures
      can modulate neurogenesis oppositely over different time window with a down
      regulation at early time and up-regulation afterwards.

PMID- 17008044
TI  - A case of acute cerebellitis accompanied by autoantibodies against glutamate
      receptor delta2.
AB  - A 13-year-old boy presented with a six-day history of headache and gradually
      developed severe meningeal irritation symptoms. Brain magnetic resonance imaging
      revealed left cerebellar swelling and obstructive hydrocephalus. Then he showed
      transient ataxia, but recovered without any sequelae soon after high dose steroid
      therapy. IgG type of autoantibodies against glutamate receptor delta2
      (GluRdelta2) were detected in the serum, but not in the cerebrospinal fluid in
      his early clinical course. It was suggested that autoantibodies against
      GluRdelta2 might not have injured the tissue due to the immunological action, but
      might be induced as a consequence of cerebellar damage. Early steroid treatment
      for acute cerebellitis might have been effective to prevent the progress of the
      disease and improve the prognosis.

PMID- 17008045
TI  - Protein modification in aging: an update.
AB  - Post-translational modifications of proteins are an important biologic tool for
      the production of various protein species from a single gene, which may vary in
      conformation, function, biologic half-life and complex formation with other
      proteins. The present minireview summarizes a few selected research observations
      important for the role of post-translational modifications in biologic aging and
      age-related diseases, including farnesylation, methylglyoxal-derivatization,
      transglutaminase pathways and the formation of 3-nitrotyrosine and 2-oxo
      histidine in vivo.

PMID- 17008046
TI  - [The physician facing legal procedures: points of view of the physician and the
      lawyer].

PMID- 17008047
TI  - Adaptive response of microglial cells to in vitro infection by Candida albicans
      isolates with different genomic backgrounds.
AB  - It has been recently demonstrated that Candida albicans isolates with distinct
      genomic backgrounds (namely, b and c genotypes) express different susceptibility
      to antifungal activity by human monocytes in vitro. We show here that, although
      comparable in their ability to undergo dimorphic transition and in susceptibility
      to phagocytosis by microglial cells, the b and c isolates show striking
      differences in terms of intracellular survival. Only the c genotype resists
      indeed to intracellular killing and eventually replicates inside microglial
      cells, that in turn respond to fungal infection, preferentially towards the c
      genotype, with nuclear factor-kappaB (NF-kappaB) activation and increased
      Mip1alpha production. These data indicate that C. albicans-microglial cell
      interaction is strictly dependent upon fungal genotype, strengthening the
      potential significance of genotyping as prognostic parameter in clinical
      infections by C. albicans.

PMID- 17008048
TI  - Inflammatory responses to psychological stress in fatigued breast cancer
      survivors: relationship to glucocorticoids.
AB  - Fatigue is a common problem following cancer treatment and our previous studies
      suggest that a chronic inflammatory process might contribute to cancer-related
      fatigue. However, immune responses to challenge have not yet been evaluated among
      individuals with cancer-related fatigue, and it is not known what mechanisms
      drive increased levels of inflammatory markers in fatigued cancer survivors. We
      have previously reported that fatigued breast cancer survivors show a blunted
      cortisol response to an experimental psychological stressor. In this report, we
      focus on inflammatory responses to this stressor and their relationship to
      circulating glucocorticoids and cellular sensitivity to glucocorticoid
      inhibition. Relative to non-fatigued control survivors, participants experiencing
      persistent fatigue showed significantly greater increases in LPS-stimulated
      production of IL-1beta and IL-6 following the stressor (Group x Time interaction:
      p<.05). Fatigued participants did not show any difference in cellular sensitivity
      to cortisol inhibition of cytokine production, but they did show significantly
      less salivary cortisol increase in the aftermath of the stressor. Moreover,
      blunted cortisol responses were associated with significantly increased
      production of IL-6 in response to LPS stimulation (p<.05). These data provide
      further evidence of enhanced inflammatory processes in fatigued breast cancer
      survivors and suggest that these processes may stem in part from decreased
      glucocorticoid response to stress.

PMID- 17008049
TI  - Association between exposure to persistent organohalogen pollutants and
      epididymal and accessory sex gland function: multicentre study in Inuit and
      European populations.
AB  - Exposure to persistent organochlorine pollutants (POPs) may have negative impact
      on male reproductive function. We, therefore, investigated the association
      between serum levels of POPs and epididymal and accessory sex gland function.
      Serum levels of CB-153, p,p'-DDE and seminal markers of epididymal [neutral-alpha
      glucosidase (NAG)], prostatic [prostate specific-antigen (PSA)] and zinc, and
      seminal vesicle function (fructose) were measured from 135 Swedish fishermen and
      fertile men from Greenland (n=163), Warsaw, Poland (n=167) and Kharkiv, Ukraine
      (n=158). Multiple linear regression analyses, adjusting for potential
      confounders, were employed using both continuous and categorized exposure
      variables. Both exposure and outcome variables were log transformed. Considering
      the consistency between models with either continuous or categorized CB-153
      levels, negative associations with the activity of NAG were found among
      Greenlandic men (mean difference 7.0 mU/ejaculate, 95% CI 3.0, 34), and in the
      aggregated cohort (mean difference 4.0 mU/ejaculate, 95% CI -0.2, 8.0). A
      positive association was observed between CB-153 and PSA as well as zinc among
      Kharkiv men. In the Swedish cohort, a negative association was found between CB
      153 and fructose. In conclusion, the negative effects of POP on sperm motility,
      observed in the same study population might partly be caused by post-testicular
      mechanisms, involving a decreased epididymal function.

PMID- 17008050
TI  - ATM regulates ionizing radiation-induced disruption of HDAC1:PP1:Rb complexes.
AB  - Ionizing radiation elicits signaling events that coordinate DNA repair and
      interruption of cell cycle progression. We previously demonstrated that ionizing
      radiation (IR) of cells activates nuclear protein phosphatase-1 (PP1) by
      promoting dephosphorylation of Thr320, an inhibitory site in the enzyme and that
      the ATM kinase is required for this response. We sought to identify potential
      targets of IR-activated PP1. Untreated and IR-treated Jurkat cells were labeled
      with (32)P orthophosphate, and nuclear extracts were subjected to microcystin
      affinity chromatography to recover phosphatase complexes that were analyzed by 2D
      PAGE and mass spectrometry. Several proteins associated with protein phosphatases
      demonstrated a significant decrease in (32)P intensity following IR, and one of
      these was identified as HDAC1. Co-immunoprecipitation revealed complexes
      containing PP1 with HDAC1 and Rb in cell extracts. In response to IR, there was
      an ATM-dependent activation of PP1, dephosphorylation of HDAC1, dissociation of
      HDAC1-PP1-Rb complexes and increased HDAC1 activity. These results suggest that
      IR regulates HDAC1 phosphorylation and activity through ATM-dependent activation
      of PP1.

PMID- 17008051
TI  - Zn2+-induced NF-kappaB-dependent transcriptional activity involves site-specific
      p65/RelA phosphorylation.
AB  - Zinc is an essential micronutrient, but is proinflammatory when inhaled into the
      lung. While it is recognized that zinc exposure of airway epithelial cells
      activates the transcription factor NF-kappaB and increases the expression of
      inflammatory cytokines to mediate this response, the underlying mechanism of NF
      kappaB activation remains to be characterized. In this study, we investigated
      these Zn2+-induced signaling mechanisms in the BEAS-2B human airway epithelial
      cell line. Fifty micromolars Zn2+ induced NF-kappaB-dependent transcriptional
      activity. However, this occurred independently of IkappaBalpha degradation, an
      essential event in activation of the canonical NF-kappaB pathway, which is
      induced by physiological stimuli such as TNFalpha and IL-1beta. We also observed
      that 50 microM Zn2+ exposure caused p65/RelA phosphorylation on Ser 276, Ser 529,
      and Ser 536 in both cytoplasmic and nuclear cell fractions. Mutational analysis
      pointed to Ser 536 of p65/RelA as the determinant of Zn2+-induced NF-kappaB
      transactivation in BEAS-2B cells. Pharmacological inhibition of IKKalpha/beta
      activity reduced both Zn2+-induced p65/RelA phosphorylation at Ser 536 and NF
      kappaB-dependent transcriptional activity, suggesting that IKKalpha/beta is
      necessary for these Zn2+-induced effects. Taken together, these data show that
      exposure to supraphysiological concentrations of Zn2+ induces NF-kappaB-dependent
      transcription through an alternate mechanism, suggesting a novel pathway for
      cellular responses to environmental stress.

PMID- 17008052
TI  - Extended vertical lower trapezius island myocutaneous flap for reconstruction of
      cranio-maxillofacial defects.
AB  - This study explored an effective method for repairing cranio-maxillofacial soft
      tissue defects following radical craniofacial surgery in four patients with
      malignant tumours involving the skull base and frontal region. The large cranio
      maxillofacial soft-tissue defects were reconstructed using an extended vertical
      lower trapezius island myocutaneous flap based on the transverse cervical artery.
      The flap was 8-12 cm long and 5-7 cm wide. No major flap failure occurred, and
      there was no shoulder dysfunction. The patients were followed for 3-12 months.
      One patient suffered a local recurrence, and another died of lung metastasis 12
      months postoperatively. The extended vertical lower trapezius island myocutaneous
      flap is a simple, reliable and large flap. It is preferred for reconstructing
      cranio-maxillofacial soft-tissue defects when a pedicled flap is used following
      craniofacial surgery for cancer.

PMID- 17008054
TI  - Patients' perceived health status following primary surgery for oral and
      oropharyngeal cancer.
AB  - How oral and oropharyngeal cancer patients view their 'quality of life' is of
      fundamental importance. Any differences seen in their health state compared with
      normative data and with other disease conditions allows a wider perspective on
      their outcome after surgery. A cross-sectional postal survey was undertaken of
      patients treated for oral/oropharyngeal squamous cell carcinoma by primary
      surgery using the University of Washington Quality of Life Questionnaire Version
      4 (UW-QOL v4) and the EuroQol EQ-5D. Of 348 patients surveyed, 224 returned
      analysable forms, (response rate 64%). In the EQ-5D items, 40% of the group
      reported a problem in walking, 23% with self-care, 44% in performing usual
      activities, 50% with pain or discomfort and 33% with anxiety or depression. The
      mean overall health visual analogue scale (VAS) score was 74 (SE 1) minimum 30
      and maximum 100. The mean utility (health index) score was 0.75 (SE 0.02) minimum
      -0.18 and maximum 1.0. Compared to national reference data, patients in our
      cohort of under 60 years of age fared significantly worse than expected for their
      age but this was not so for older patients. There were strong correlations
      between appropriate domains of the EQ-5D and UW-QOLv4 and between UW-QOL global
      measures and EQ-5D VAS.

PMID- 17008053
TI  - Complications in maxillary distraction using the RED II device: a retrospective
      analysis of 21 patients.
AB  - Rigid external distraction osteogenesis (DO) in the treatment of midface
      hypoplasia has been shown to be effective and safe, but there have been several
      case reports on complications. Here is presented an overview of the complications
      in a series of 21 patients with various craniofacial anomalies. All patients were
      treated using the rigid external distraction II (RED II) device after Le Fort I
      or III osteotomy. Distraction started 1 week postoperatively and continued until
      Class I occlusion was achieved; it was then continued to include a 15%
      overcorrection. All data were collected and categorized retrospectively from the
      patients' files. After a mean period of distraction of 34 days, 42 complications
      were reported in six different categories. Pin loosening (42.9%) and frame
      migrations (28.6%) were the most common complications. Of the frame migrations
      25% were traumatic. Intracranial penetration of one fixation pin occurred during
      removal of the RED II device in one patient. From these results it can be deduced
      that application of the RED II device is associated with a substantial number of
      specific complications that mainly concern the pins of the halo-frame. The
      stability of the device is discussed as the distraction distance achieved was
      less than expected.

PMID- 17008055
TI  - Pacinian neuroma in adipose herniation of the buccal mucosa.
AB  - An interesting case of a trauma-induced tender mass of the buccal mucosa in a 45
      year-old man was presented. Following surgery, the patient was relieved from
      pain. Microscopically, the mature adipose tissue is unique in that it contained a
      single enlarged Pacinian corpuscle near the deep margin. This is the hitherto
      undescribed intraoral lesion of Pacinian neuroma in the herniated buccal fat pad.

PMID- 17008056
TI  - Soft-tissue chondroma of the masticatory space.
AB  - Soft-tissue chondroma is an infrequent, benign, cartilaginous tumour that is
      uncommon in the head and neck region. Single-location chondromas rarely evolve
      into malignant neoplasms. Chondromas are composed of hyaline cartilage with focal
      calcification. There have been a few reports published of cases of soft-tissue
      chondroma of the neck and parapharyngeal space. Here is described a new location
      of this tumour in the masticatory space.

PMID- 17008057
TI  - Altered expression of hippocampal dentate granule neuron genes in a mouse model
      of human 22q11 deletion syndrome.
AB  - Hemizygous deletion of a 3 Mb region of 22q11.2 is found in 1/4000 humans and
      produces 22q11 deletion syndrome (22q11DS). Up to 35% of 22q11DS patients develop
      schizophrenia, making it the second highest risk factor for schizophrenia. A
      mouse model for 22q11DS, the Df1/+ mouse, carries a hemizygous deletion in a
      region syntenic with the human deletion. Df1/+ mice are mostly viable but display
      deficits in prepulse inhibition and learning and memory, two common traits of
      schizophrenia thought to result, at least in part, from defects in hippocampal
      neurons. We used oligonucleotide microarrays and QRT-PCR to evaluate gene
      expression changes in hippocampal dentate granule neurons of Df1/+ mice versus
      wild-type littermates (n=12/group). The expression of only 287 genes changed with
      p value significance below 0.05 by microarray, yet 12 of the 21 Df1 region genes
      represented on the array showed highly significantly reduced expression compared
      to wild-type controls (33% on average, p values from 10(-3) to 10(-7)). Variants
      in two of these genes, COMT and PRODH, have been linked with schizophrenia.
      Overlap of the 287 genes with the reportedly reduced expression of mitochondrial,
      ubiquitin/proteasome, and synaptic plasticity genes in schizophrenia dentate
      granule neurons, was not significant. However, modest increases in expression of
      mitochondrial electron transport genes were observed in the Df1/+ mice. This
      perhaps indicates a compensation for mitochondrial dysfunction caused by the
      strongly reduced expression of the Df1 region-encoded mitochondrial enzymes
      proline dehydrogenase (Prodh) and thioredoxin reductase 2 (Txnrd2).

PMID- 17008058
TI  - Lack of care for diabetes among schizophrenia patients.

PMID- 17008059
TI  - Macrophage-derived chemokine (MDC)/CCL22 produced by monocyte derived dendritic
      cells reflects the disease activity in patients with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a recurrent inflammatory skin disease
      characterized by high serum levels of IgE and Th2-type cytokines such as IL-4, IL
      5 or IL-13. Chemokines attract leukocytes in inflamed tissues. We have previously
      found that thymus and activation regulated chemokine (TARC)/CCL17 and macrophage
      derived chemokine (MDC)/CCL22 are highly secreted in the plasma levels of AD
      patients. Dendritic cells (DCs) are antigen-presenting cells that are divided
      into two subgroups including monocyte derived DCs (MoDCs) and plasmacytoid DCs
      (pDCs). OBJECTIVES: The aim of the study was to elucidate CCL17 and CCL22
      production by MoDCs in AD patients, psoriasis vulgaris (PsV) patients and healthy
      controls (HC). METHODS: MoDCs were obtained from AD patients, PsV patients or HC
      and were cultured. In addition, the chemokine levels were measured in the
      supernatants. RESULTS: We found that the CCL22 levels produced by MoDCs in AD
      patients to be significantly higher than those of PsV patients and HC. There was
      a significant correlation between the CCL22 levels produced by MoDCs and the
      SCORAD index. No significant difference in the CCL17 levels produced by MoDCs was
      detected among AD patients, PsV patients or HC. Immunosuppressive drugs such as
      dexamethasone (Dex), tacrolimus and cyclosporine (Cys) inhibited the CCL22
      production by MoDCs in the AD patients. CONCLUSION: These data suggest that the
      CCL22 level produced by MoDCs thus reflects the disease activity of AD and it may
      also play an important role regarding the production of CCL22 in the pathogenesis
      of AD.

PMID- 17008060
TI  - Two novel mutations detected in Japanese patients with oculocutaneous albinism.

PMID- 17008061
TI  - Identification of a novel mutation and a genetic polymorphism of EVER1 gene in
      two families with epidermodysplasia verruciformis.
AB  - BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare autosomal recessive
      disease. The main clinical features include three kinds of lesions, high risk of
      skin cancer, and abnormal susceptibility to HPV 5 and 8. Recent studies have
      shown that mutations in EVER1 and EVER2 genes are responsible for the condition.
      OBJECTIVE: In the present study, we investigated the molecular basis of EV in two
      families with EV. METHODS: PCR and direct sequencing of the EVER1 and EVER2 genes
      were used to identify and confirm the mutations in our probands in the two
      families. Direct sequencing and SacI digestion were used to detect the
      polymorphism of exon 6. RESULTS: Sequencing of the EVER1 and EVER2 genes revealed
      a novel mutation and a genetic polymorphism. The novel mutation by inserting
      CATGT after nucleotide 916 in exon 9 resulted in a nonsense mutation and a
      premature termination codon. Direct sequencing and SacI digestion revealed
      genotype frequencies of C457T, 457T, and 457C alleles in 16 individuals of EV
      families were of 9, 3, and 4, which were 26, 0, and 24 in 50 unrelated normal
      controls, respectively. To our knowledge, the novel mutation and genetic
      polymorphism have not been described in literatures. CONCLUSIONS: The growing
      number of mutations in EV pedigrees supports the hypothesis that EVER1 and EVER2
      are the molecular basis of EV.

PMID- 17008062
TI  - No effect of heparin on IgE-dependent and IgE-independent histamine release in
      human skin in vivo: a microdialysis study.

PMID- 17008063
TI  - Identification of population dynamics in sulfate-reducing consortia on exposure
      to sulfate.
AB  - The microbial population structure and function of a mixed culture of sulfate
      reducing bacteria (SRB) maintained in anaerobic continuous bioreactors were
      tracked before and after a major perturbation, which involved the addition of
      sulfate to the influent of a bioreactor when operated at steady state at 35
      degrees C, pH 7.8 and a 2.5 day residence time with feed stream containing 10 and
      15 kg m(-3) sulfate as terminal electron acceptor and 19.6 and 29.4 kg m(-3)
      ethanol as carbon source and electron donor, respectively. The population
      structure determined by fluorescence in situ hybridization (FISH), by using 16S
      rRNA-targeted oligonucleotide probes, was linked to the functional performance of
      the SRB in the reactor. Hybridization analysis using these 16S rRNA-targeted
      oligonucleotide probes revealed that a high concentration of sulfate was toxic
      for Desulfobacterium and Desulfobulbus. On the other hand, the Desulfococcus
      group was found to be the most dominant group of SRB in the feed stream
      containing 15 kg m(-3) sulfate as terminal electron acceptor and 29.4 kg m(-3)
      ethanol as carbon source and electron donor.

PMID- 17008064
TI  - Utility of the polymerase chain reaction in the diagnosis of tuberculous
      meningitis.
AB  - Due to inconsistent clinical presentations and the lack of a rapid, sensitive and
      specific test, tuberculous meningitis (TBM) is particularly difficult to
      diagnose. The present study was carried out to determine the utility of the
      polymerase chain reaction (PCR) using INS primers in the diagnosis of TBM and to
      compare the efficacy of two different DNA extraction protocols. Fifty-seven
      cerebrospinal fluid (CSF) samples from suspected cases of meningitis -- 30
      definitive/possible TBM and 27 non-TBM -- were processed for microscopy, culture
      and PCR. Results of computer tomographic (CT) scan findings were noted. The
      results of smear, culture and PCR were compared using culture and/or clinical
      response to treatment as the gold standard. The sensitivity of microscopy,
      culture, CT scan and PCR was 3.3%, 26.7%, 60.0% and 66.7%, respectively. PCR
      following QIAmp DNA extraction had a sensitivity of 66.7% compared to PCR
      following a DNA extraction protocol based on the use of cetyl trimethyl ammonium
      bromide (CTAB) (50%). PCR was positive in all culture-positive CSF samples using
      either extraction method. PCR is a rapid and sensitive technique; above all, it
      can diagnose tuberculous meningitis at a very early stage.

PMID- 17008065
TI  - Cell-cell signaling, cyclic di-GMP turnover and regulation of virulence in
      Xanthomonas campestris.
AB  - The synthesis of virulence factors in the plant pathogen Xanthomonas campestris
      pathovar campestris is regulated by cell-cell signaling mediated by a diffusible
      signal factor (DSF), and by the RpfC/RpfG two-component regulatory system. Recent
      findings have indicated that the perception of the DSF signal requires the RpfC
      sensor and is linked to the degradation of the intracellular second messenger
      cyclic di-GMP by the HD-GYP domain regulator RpfG.

PMID- 17008066
TI  - Comparative in vitro activity of ertapenem against extended-spectrum beta
      lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated in Spain.
AB  - The in vitro activity of ertapenem was tested against extended-spectrum beta
      lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolated in
      Spain. Ertapenem activity was similar to that of imipenem and meropenem and
      better than that of the other antimicrobials tested. No differences in activity
      were observed regarding the origin of the isolates or type of ESBL produced.

PMID- 17008067
TI  - First report of Listeria monocytogenes endocarditis treated with linezolid.

PMID- 17008068
TI  - Lipopolysaccharide attenuates mRNA levels of several adenylyl cyclase isoforms in
      vivo.
AB  - Signals that elevate intracellular levels of cyclic adenosine monophosphate
      (cAMP) are among the factors that control lipopolysaccharide (LPS)-mediated
      inflammatory mediator production by macrophages. cAMP signaling is also involved
      in maintaining body functions that are commonly impaired in sepsis, including the
      endothelial cell barrier function and heart function. Several agents successfully
      used for sepsis intervention target cAMP signaling, and it was recently shown
      that liver and lung may be protected from inflammation injury by cAMP-elevating
      phosphodiesterase inhibitors. Here, we show that LPS attenuates adenylyl cyclase
      (AC) mRNA levels in liver, lung, heart, spleen and kidney in an animal model of
      endotoxemia, and in macrophages from liver and lung. In particular, AC5, AC6, AC7
      and AC9 mRNA were reduced in most tissues examined and in tissue macrophages. In
      Kupffer cells, prostaglandin E2-mediated cAMP production was inhibited by LPS
      treatment. The reduction in AC mRNA by LPS would be expected to lead to a lowered
      potential for cAMP production in most organs, and in particular, changes in AC6
      mRNA may affect endothelial cell barrier function and heart function. In
      contrast, AC4 mRNA was elevated in heart and lung. The present work indicates a
      possible mechanism for LPS-mediated alteration of cAMP signaling in vivo.

PMID- 17008070
TI  - [Drugs news].

PMID- 17008069
TI  - Drosophila alpha-actinin in ovarian follicle cells is regulated by EGFR and Dpp
      signalling and required for cytoskeletal remodelling.
AB  - alpha-Actinin is an evolutionarily conserved actin filament crosslinking protein
      with functions in both muscle and non-muscle cells. In non-muscle cells,
      interactions between alpha-actinin and its many binding partners regulate cell
      adhesion and motility. In Drosophila, one non-muscle and two muscle-specific
      alpha-actinin isoforms are produced by alternative splicing of a single gene. In
      wild-type ovaries, alpha-actinin is ubiquitously expressed. The non-muscle alpha
      actinin mutant Actn(Delta233), which is viable and fertile, lacks alpha-actinin
      expression in ovarian germline cells, while somatic follicle cells express alpha
      actinin at late oogenesis. Here we show that this latter population of alpha
      actinin, termed FC-alpha-actinin, is absent from the dorsoanterior follicle
      cells, and we present evidence that this is the result of a negative regulation
      by combined Epidermal growth factor receptor (EGFR) and Decapentaplegic
      signalling. Furthermore, EGFR signalling increased the F-actin bundling activity
      of ectopically expressed muscle-specific alpha-actinin. We also describe a novel
      morphogenetic event in the follicle cells that occurs during egg elongation. This
      event involves a transient repolarisation of the basal actin fibres and the
      assembly of a posterior beta-integrin-dependent adhesion site accumulating alpha
      actinin and Enabled. Clonal analysis using Actn null alleles demonstrated that
      although alpha-actinin was not necessary for actin fibre formation or
      maintenance, the cytoskeletal remodelling was perturbed, and Enabled did not
      localise in the posterior adhesion site. Nevertheless, epithelial morphogenesis
      proceeded normally. This work provides the first evidence that alpha-actinin is
      involved in the organisation of the cytoskeleton in a non-muscle tissue in
      Drosophila.

PMID- 17008071
TI  - Cell-nuclear data reduction and prognostic model selection in bladder tumor
      recurrence.
AB  - OBJECTIVE: The paper aims at improving the prediction of superficial bladder
      recurrence. To this end, feedforward neural networks (FNNs) and a feature
      selection method based on unsupervised clustering, were employed. MATERIAL AND
      METHODS: A retrospective prognostic study of 127 patients diagnosed with
      superficial urinary bladder cancer was performed. Images from biopsies were
      digitized and cell nuclei features were extracted. To design FNN classifiers,
      different training methods and architectures were investigated. The unsupervised
      k-windows (UKW) and the fuzzy c-means clustering algorithms were applied on the
      feature set to identify the most informative feature subsets. RESULTS: UKW
      managed to reduce the dimensionality of the feature space significantly, and
      yielded prediction rates 87.95% and 91.41%, for non-recurrent and recurrent
      cases, respectively. The prediction rates achieved with the reduced feature set
      were marginally lower compared to the ones attained with the complete feature
      set. The training algorithm that exhibited the best performance in all cases was
      the adaptive on-line backpropagation algorithm. CONCLUSIONS: FNNs can contribute
      to the accurate prognosis of bladder cancer recurrence. The proposed feature
      selection method can remove redundant information without a significant loss in
      predictive accuracy, and thereby render the prognostic model less complex, more
      robust, and hence suitable for clinical use.

PMID- 17008073
TI  - Levels of the n-3 fatty acid eicosapentaenoic acid in addition to those of alpha
      linolenic acid are significantly raised in blood lipids by the intake of four
      walnuts a day in humans.
AB  - BACKGROUND AND AIMS: Ingestion of alpha linolenic acid (ALA), with the richest
      source among dry fruits such as walnuts, is associated with cardiovascular
      prevention. The aim of this study was to selectively evaluate the effects of
      moderate walnut consumption on the levels of ALA and its metabolic derivatives in
      human blood. METHODS AND RESULTS: After a 2-week run-in period, 10 volunteers
      consumed 4 walnuts per day (in addition to their habitual diet) for 3 weeks.
      Fatty acid profiles, with special attention to levels of ALA and long chain
      polyunsaturated fatty acids (LC-PUFA), were assessed in blood drops collected
      from fingertips. The data indicate that the administration of a few walnuts a day
      for 3 weeks significantly increases blood levels, not only of ALA (from 0.23+/
      0.07 SD to 0.47+/-0.13 SD), but also of its longer chain derivative
      eicosapentaenoic acids (EPA) (from 0.23+/-0.37 to 0.82+/-0.41) with levels
      remaining elevated over basal values after washout. CONCLUSION: The findings of
      this pilot study indicate that plant ALA in appropriate food items favourably
      affects the n-3 LC-PUFA status.

PMID- 17008072
TI  - Evaluating the correlation and prediction of trunk fat mass with five
      anthropometric indices in Chinese females aged 20-40 years.
AB  - BACKGROUND AND AIMS: Obesity is a worldwide problem, and excess trunk fat mass
      (FM(trunk)) has been associated with an increased risk of diseases. The early
      measurement of FM(trunk) has potential importance to evaluate trunk obesity. We
      sought to evaluate the correlation and predication of FM(trunk) with five
      anthropometric indices in Chinese females. METHODS AND RESULTS: A sample of 850
      China females aged 20-40 years were recruited and divided into four age groups
      with a 5-year range in each group. Five anthropometric indices were measured or
      calculated. FM(trunk) in kg was measured using a dual-energy X-ray absorptiometry
      scanner. Principal component analysis (PCA) and multiple regression analysis were
      performed to develop prediction equations. There was an increasing trend of
      FM(trunk) and five anthropometric indices in successively older age groups. Four
      formed principal components (PCs) interpreted over 99% of the total variation of
      five relative anthropometric indices in all age groups. Regression analyses
      showed that four PCs combined explained a greater variance (R(2)=45.2-81.6%) in
      FM(trunk) than did each of the five indices alone (R(2)=2.4-72.2%). CONCLUSIONS:
      Our results suggested that there is an increasing trend of FM(trunk) and five
      anthropometric indices with aging; that age obviously influences the relationship
      of FM(trunk) and the anthropometric indices studied; and that the accuracy of
      predicting the FM(trunk) using five anthropometric indices combined is greater
      than using the five indices alone.

PMID- 17008074
TI  - Beneficial effects of physical exercise on hypertension and cardiovascular
      adverse remodeling of diet-induced obese rats.
AB  - BACKGROUND AND AIMS: Obesity is present among all age groups and in all
      socioeconomic groups. This study on obese rats aims to quantify the beneficial
      effects of physical exercise on blood pressure (BP), the heart, the elasticity
      and resistance of arteries. METHODS AND RESULTS: Obese male Wistar rats, (obesity
      due to a high fat diet with 30% fat), and non-obese rats, were assigned to four
      groups (n=5): sedentary obese; exercise-practice obese; sedentary control; and
      exercise-practice control (motor treadmill for 13 weeks). Their organs were
      studied through light microscopy and stereology. The diet-induced obesity caused
      mild hypertension with adverse cardiovascular changes. Physical exercise
      diminished the alterations associated with BP elevation and obesity. The pressure
      lowering effect observed in obese rats submitted to physical exercise improved
      the myocardial vascularization and the aortic and the carotid wall structure by
      reducing the thickness and normalizing both the elastic lamellae and the smooth
      muscle cells. The adaptive response of the gluteus superficialis muscle to
      physical exercise also improved the peripheral resistance arteries of obese rats.
      CONCLUSION: Current research supports the notion of physical exercise as a
      potential non-pharmacological antihypertensive treatment for diet-induced obesity
      hypertension.

PMID- 17008075
TI  - Gene-alcohol interactions in the metabolic syndrome.
AB  - AIMS: Recent studies have reported that moderate alcohol consumption is
      associated with a lesser prevalence of the metabolic syndrome (MetS). However,
      this relationship is still confusing and the presence of gene-environment
      interactions has been suggested. Our aim is to summarize evidence for gene
      alcohol interactions in the MetS. DATA SYNTHESIS: Research in gene-alcohol
      interactions applied to MetS is very complex due to the difficulties surrounding
      the definition of phenotype, environment and genotype, as well as in estimating
      the influence of the social context. In the MetS there is a constellation of
      metabolic disturbances the definition of which is still changing. Thus, most
      studies that have reported on gene-alcohol interactions have done so by analyzing
      isolated components. Likewise, the definition of alcohol consumption is also
      complex given that apart from the amount of ethanol consumed, the type of drink,
      the frequency of consumption, etc., may be important. No less difficult is the
      definition of genotype as there are many candidate genes involved, including not
      only those relevant for each phenotype studied, but also those related with
      alcohol metabolism, as well as those related to alcohol intake. CONCLUSIONS:
      Although various studies exist that show statistically significant interactions
      between alcohol consumption and MetS components, a greater integration of
      variables as well as greater homogeneity in definitions is required.

PMID- 17008076
TI  - Effect of poloxamers on nifedipine microparticles prepared by Hot Air Coating
      technique.
AB  - The Hot Air Coating (HAC) technique was used to prepare microparticles consisting
      of 30% nifedipine coated with different lipid mixtures. Cetearyl alcohol or
      cetearyl alcohol and 5% or 15% of a poloxamer (Pluronic F68 or Pluronic F127)
      were used as excipients. HAC products were analyzed in terms of morphology,
      flowability, thermal properties and nifedipine release behaviour, in order to
      elucidate the role played by the Pluronics on the physico-chemical and
      pharmaceutical characteristics of microparticles. HAC particles were spherical
      and their surface appeared scale-worked; thermal studies demonstrated the
      existence of relevant interactions among the system components and the
      dissolution experiments led to the hypothesis that the drug is released primarily
      by diffusion through the lipid coating: the poloxamer and its concentration have
      a significant influence on the pharmaceutical properties of the dosage form, as
      shown by the a parameter of Weibull model.

PMID- 17008077
TI  - Comparative study on the forefoot and hindfoot intrinsic muscles of some
      cavioidea rodents (Mammalia, Rodentia).
AB  - The present study compares the forefoot and hindfoot musculature of five
      representative species of Cavioidea rodents. In all species, the musculature of
      both forefeet and hindfeet have the same array regardless of the absence of digit
      I in the manus of Hydrochaeris hydrochaeris and Cavia porcellus. Our results
      suggest a tendency in these species towards a three-digit system, with a
      functional loss of digit V and a predominance of digit III in their forefeet. In
      the same way, the muscular reduction of digit I in the other rodents analyzed
      indicates a four-digit system with predominance of digit II in Myoprocta acouchy
      and Dasyprocta leporina and of digit V in Agouti paca. There seems to be an
      association between the muscular arrangement and functional axis of the foot,
      raising the general question why this axis runs between the third and forth
      digit, or along the third digit.

PMID- 17008078
TI  - Quantification of cell size distribution as applied to the growth of
      Corynebacterium glutamicum.
AB  - It is known that the cell size is related to the physiological state of a cell.
      Therefore, cell size distribution directly reflects the average physiological
      properties of the cell culture. Cell size distribution can be enumerated by image
      analysis, flow cytometry and coulter counter. In this study, image analysis was
      used to characterize the cell size distribution during the growth of
      Corynebacterium glutamicum and was further analyzed by a distribution function.
      The parameters of the distribution function indicate the mean value and spread of
      the distribution. Analysis demonstrated that the maximum specific growth rate was
      higher (0.67h(-1)) for the growth obtained through serial dilution of seed as
      compared to growth from a normal seed culture (0.53h(-1)). This was due to a
      greater percentage of the cell population being in the state of division for the
      growth through serial dilution in the mid-log phase. The measurement of the cell
      size distribution demonstrated that the average cell size decreased during the
      course of growth. The distribution function was also used to enumerate the
      average specific growth rate of both the conditions of the culture. The
      demonstrated methodology can be used to predict an average growth property of a
      cell culture.

PMID- 17008079
TI  - Characterisation of Pseudomonas aeruginosa isolated from freshwater culture
      systems.
AB  - Members of the genus Pseudomonas are important phytopathogens and agents of human
      infections, while other strains and species exhibit bioremediation and biocontrol
      activities. Species-specific detection of Pseudomonas species in the environment
      may help to gain a more complete understanding of the ecological significance of
      these microorganisms. The objective of present study was comparative analysis of
      biochemically and PCR based confirmed 10 isolates of Pseudomonas aeruginosa (6
      from fish intestine and 4 from pond sediment). PCR-ribotyping and PAGE revealed
      that there was extensive heterogeneity at the genetic and protein levels. Both
      genetic and phenotypic heterogeneity were more in the sediment isolates compared
      to the fish isolates. SDS-PAGE clearly demonstrated the differences between fish
      and sediment isolates as evident from the higher range of protein profiling. In
      antibiotic sensitivity test no habitat specific antibiogram was obtained. Zinc
      adversely affected the DNA of all the isolates to be amplified by PCR as DNA
      banding pattern was different from normal DNA in stressed DNA. Thus stress,
      particularly, zinc may interfere monitoring of Pseudomonas by PCR.

PMID- 17008080
TI  - Kinetic study of cytokines production by human peripheral blood mononuclear cells
      in response to Brucella DNA.
AB  - In spite of reports on cytokines induction by the Brucella DNA in murine model,
      there is no comparison between pathogenic and appropriate vaccine strains in
      human. We investigated the cytokines profile of human peripheral blood
      mononuclear cells (PBMCs) induced by DNA extracted from pathogenic isolates of
      Brucella melitensis and B. abortus as well as Rev1 and S19; the appropriate
      vaccine strains. It was observed that despite differential induction of
      Interleukin(IL)-12 and IL-10 production, identical IL-12/IL-10 concentration
      ratio was obtained by all Brucella strains DNAs that was 2 after 24 h and 4 after
      5 days of incubation. In addition, IL-2 and Interferon(IFN)-gamma production were
      profoundly increased compared to the medium at day 3 and 5 respectively but IFN
      alpha was not induced. Therefore, Brucella strains DNAs are Th1 inducing
      component with similar pattern in human PBMCs.

PMID- 17008081
TI  - Humanized mouse models for organ-specific autoimmune diseases.
AB  - Murine models for human autoimmune diseases are an essential tool for studying
      pathogenesis and for identifying new therapeutic targets. Mice are not the
      natural disease host, and conventional models have proved to be poor predictors
      of efficacy and safety in recent trials aiming to translate drug and biologic
      treatments to humans. Evidently, further steps towards recapitulating human
      diseases are urgently needed, for example using transgenic predisposing human HLA
      allele(s) plus T-cell receptor(s) implicated in a representative patient's
      autoimmune disease. The latest development - humanizing most of the immune system
      by transplanting human hematopoietic stem cells into severely immunodeficient
      mice - should lead to even better modeling.

PMID- 17008082
TI  - Penicillium purpurogenum produces a family 1 acetyl xylan esterase containing a
      carbohydrate-binding module: characterization of the protein and its gene.
AB  - At least three acetyl xylan esterases (AXE I, II and III) are secreted by
      Penicillium purpurogenum. This publication describes more detailed work on AXE I
      and its gene. AXE I binds cellulose but not xylan; it is glycosylated and
      inactivated by phenylmethylsulphonyl fluoride, showing that it is a serine
      esterase. The axe1 gene presents an open reading frame of 1278 bp, including two
      introns of 68 and 61 bp; it codes for a signal peptide of 31 residues and a
      mature protein of 351 amino acids (molecular weight 36,693). AXE I has a modular
      structure: a catalytic module at the amino terminus belonging to family 1 of the
      carbohydrate esterases, a linker rich in serines and threonines, and a family 1
      carboxy terminal carbohydrate binding module (CBM). The CBM is similar to that of
      AXE from Trichoderma reesei, (with a family 5 catalytic module) indicating that
      the genes for catalytic modules and CBMs have evolved separately, and that they
      have been linked by gene fusion. The promoter sequence of axe1 contains several
      putative sequences for binding of gene expression regulators also found in other
      family 1 esterase gene promoters. It is proposed that AXE I and II act in
      succession in xylan degradation; first, xylan is attacked by AXE I and other
      xylanases possessing CBMs (which facilitate binding to lignocellulose), followed
      by other enzymes acting mainly on soluble substrates.

PMID- 17008083
TI  - Fungicides affect the production of extracellular mucilaginous material (ECMM)
      and the peripheral growth unit (PGU) in two wood-rotting basidiomycetes.
AB  - This study shows the effect of two fungicides on the production of extracellular
      mucilaginous material (ECMM) in two wood-rotting basidiomycetes and identifies a
      mechanism that might be responsible for the variation observed. Increasing
      concentrations of the fungicides copper sulphate (CuSO4) and cyproconazole in the
      growth medium increased the proportion of ECMM in the biomass of Trametes
      versicolor and Gloeophyllum trabeum. These fungicides also caused a reduction in
      the length of the peripheral growth unit (PGU) of the mycelia leading to a more
      highly branched morphology and a larger number of hyphal tips, the sites for
      active secretion of ECMM, per unit length of mycelium. It is postulated that both
      in T. versicolor and G. trabeum this change in growth leads to the increases
      observed in the proportion of ECMM in the total biomass. The implications of
      these results are discussed with a view to a potential protective role of ECMM
      against stress and toxic environments.

PMID- 17008084
TI  - Optimal bulking agent particle size and usage for heat retention and disinfection
      in domestic wastewater sludge composting.
AB  - Composting of two types of sludge produced in wastewater treatment plants, raw
      sludge (RS) and anaerobically digested sludge (ADS), has been systematically
      studied by means of the experimental design technique. The results have been
      analyzed using a full factorial experimental design in order to determine the
      optimal conditions for composting such sludges in terms of bulking agent particle
      size and bulking agent:sludge volumetric ratio, two of the key parameters to
      ensure an optimal performance of the composting process. The objective function
      selected was a simulated death kinetics of Salmonella, which was chosen as a
      model pathogen microorganism to represent the disinfection of the material. For
      both types of sludge, optimal values were found at 5mm bulking agent particle
      size and 1:1 bulking agent:sludge volumetric ratio when a Gaussian function was
      fitted to the experimental data. Pilot scale experiments using optimal values
      obtained were successfully undertaken and confirmed a full disinfection of the
      sludge by means of the composting process. A mathematical model to simulate the
      disinfection performance of a composting material is presented. The model can be
      applied to simulate the disinfection performance of a given pathogen.

PMID- 17008085
TI  - Metals, non-metals and PCB in electrical and electronic waste--actual levels in
      Switzerland.
AB  - The chemical composition of waste of small electrical and electronic equipment (s
      WEEE), a rapidly growing waste stream, was determined for selected metals (Cu,
      Sb, Hg etc.) and non-metals (Cl, Br, P) and PCBs. During a 3-day experiment, all
      output products and the s-WEEE input mass flows in a WEEE recycling plant were
      measured. Only output products were sampled and analyzed. Material balances were
      established, applying substance flow analysis (SFA). Transfer coefficients for
      the selected substances were also determined. The results demonstrate the
      capability of SFA to determine the composition of the highly heterogeneous WEEE
      for most substances with rather low uncertainty (2 sigma +/- 30%). The results
      confirm the growing importance of s-WEEE regarding secondary resource metals and
      potential toxic substances. Nowadays, the thirty times smaller s-WEEE turns over
      larger flows for many substances, compared to municipal solid waste. Transfer
      coefficient results serve to evaluate the separation efficiency of the recycling
      process and confirm--with the exception of PCB and Hg--the limitation of hand
      sorting and mechanical processing to separate pollutants (Cd, Pb, etc.) out of
      reusable fractions. Regularly applied SFA would serve to assess the efficacy of
      legislative, organizational and technical measures on the WEEE.

PMID- 17008086
TI  - Micro hole-based cell chip with impedance spectroscopy.
AB  - Electric fields can be used for the characterisation and manipulation of single
      biological cells. One approach to avoid the effect of electrode polarisation is
      to position cells on micro holes and to apply the electrical fields via the micro
      holes. For a correct characterisation and optimal manipulation, the electrical
      properties of the micro hole/cell interface must be understood. In this article,
      the electrical characteristics of a micro hole-based cell chip were investigated.
      By FEM simulation, it was estimated that the impedance measurement with micro
      hole-based chip is most dependent on the cell adhesion/spread rather than the
      intra-cellular space (contribution of intra-cellular space to the total
      impedance: 0.07% at 1 kHz, 0.3% at 1 MHz). The effective frequency range in which
      the impedance related with cell state on the hole considerably influences total
      measured impedance was below several kiloHertz. From the experiments, it was
      shown that the impedance of cell cultured on the hole at the low frequency range
      is increased during the increase of cultivation period, but is sensitively
      decreased after applying only several nanolitres of culture medium including 5%
      dimethlysulfoxide. This micro hole-based chip has a potential for monitoring the
      cell growth and the membrane integrity of even single cell without any labelling.

PMID- 17008087
TI  - Bisulfite modification of immobilized DNAs for methylation detection.
AB  - We have developed a novel method for detecting DNA methylation status of multiple
      samples, in which the DNA samples were firstly immobilized on the slide and
      treated with bisulfite directly on the chip. In this experiment, DNAs of pUC19
      plasmid were restricted by the enzymes, and ligated with a linker bearing 5'
      terminal acrylamide group at the sticky ends. Using universal acrylamide gel
      polymerization technique, a large amount of DNAs could be immobilized on the
      slide. The immobilized DNAs were converted by soaking the chip in bisulfite
      reaction mixtures for 16 h. The probes for detection of the methylation patterns
      of CpG sites hybridized with the converted DNAs on the microarray, and non
      specifically bound probes were cleaned by electrophoresis. We have optimized the
      experimental conditions of both bisulfite treatment and electrophoresis to
      increase sensitivity and specificity. The results were further validated by
      bisulfite DNA sequencing. The experiments show that the method can simplify the
      experimental processes and increase the efficiency of the bisulfite treatment.
      This novel method could be used as a convenient tool to detect the methylation
      status of the multiple genes for a large amount of samples in the future.

PMID- 17008088
TI  - Microbial imprinted polypyrrole/poly(3-methylthiophene) composite films for the
      detection of Bacillus endospores.
AB  - The fabrication of Bacillus subtilis endospore imprinted conducting polymer films
      and subsequent electrochemical detection of bound spores is reported. Imprinted
      films were prepared by absorbing spores on the surface of glassy carbon
      electrodes upon which a polypyrrole, followed by a poly(3-methylthiophene), layer
      were electrochemically deposited. Spore template release was achieved through
      soaking the modified electrode in DMSO. Binding of endospores to imprinted films
      could be detected via impedance spectroscopy by monitoring changes in Y''
      (susceptance) using Mn(II)Cl2 (0.5M pH 3) as the supporting electrolyte. Here,
      the change in Y'' could be correlated to spore densities between 10(4) and
      10(7)cfu/ml. More sensitive detection of absorbed spores was achieved by
      following endospore germination via changes in film charge as measured using
      cyclic voltammetry. Here, imprinted films were submerged in spore suspensions to
      permit absorption, heat activated at 70 degrees C for 10 min prior to
      transferring to an electrochemical cell containing germination activators. By
      using the assay format it was possible to detect 10(2)cfu/ml. The observed
      changes in film charge could be attributed to the interaction of the supporting
      conducting polymer with dipicolinic acid (DPA) and other constituents released
      from the core in the course of germination. In all cases, it was not possible to
      regenerate the imprinted films without losing electrode response. In summary, the
      study has provided proof-of-concept for fabricating microbial imprinted films
      using conducting polymers.

PMID- 17008089
TI  - Culturing neuron cells on electrode with self-assembly monolayer.
AB  - The success of neuronal implantable microsystems relies on the quality of the
      interface with neuronal cells. Depending on the application, specifically
      engineered surfaces may either prevent or enhance cell/tissue growth with an
      appropriate host response. The surface chemistry and topography have major
      effects on the cell adherence and the interaction between the tissue and devices.
      We report on a simple technique to precisely explant cortical neurons in a serum
      free medium on 2D electrode arrays and investigated the pad size effect on neuron
      cell culture and immobilization. We produced gold patterns on glass substrates
      using microfabrication processes. 11-Amino-1-undecanethiol self-assembled
      monolayer was coated only on the gold surface. Cortical neurons were cultured on
      the arrays to examine the dependence of neuron growth and cells distribution on
      pad size. We found that the terminal functional groups of the highly oriented 11
      amino-1-undecanethiol thin film are essential for generating cell-adhesive areas
      for the rat cortical neurons. A 50 microm x 50 microm SAM pad size was found to
      be suitable for single cortical neuron immobilization, while the larger pads
      provide excellent neuron coverage. This technology may enable precise and
      localized neuron stimulation and surveillance for both biological research and
      medical applications.

PMID- 17008090
TI  - Using DNA microarrays to study natural variation.
AB  - The emerging field of genomics examines the relationship between genetic and
      phenotypic variation by describing and analyzing patterns of natural variation on
      a genome-wide scale. In this endeavor, an important tool is the use of
      microarrays, which enable simultaneous screening of thousands of assays.
      Microarrays were originally designed for the detection of differences between
      samples and are thus ideally suited to high-throughput studies of natural
      variation. Novel microarray platforms enable the high throughput survey of
      variation at multiple levels, including DNA sequences, gene expression, protein
      binding, and methylation. However, most microarray data analysis tools, notably
      normalization methods, were developed for experiments in which only few features
      differed between samples. In studies of natural variation, this assumption does
      not always hold, raising a number of new challenges.

PMID- 17008091
TI  - Scanning the human genome for signals of selection.
AB  - The search for adaptive evolution in the human genome has reached a new era with
      the advent of genome-wide surveys of genetic variation. However, making sense,
      let alone use, of such experiments is far from straightforward. Key problems
      include the way in which the data have been collected, the need to control for
      factors such as population history and variable recombination rates, which
      influence the discovery rates for both true and false positives, and the inherent
      difficulty of falsification. Nevertheless, recent work has shown that genome
      scans can be used to identify both functional polymorphisms underlying selected
      traits and entire classes of genes enriched for signals of adaptation.

PMID- 17008092
TI  - Does marital status and altered contact with the social network predict
      colorectal cancer survival?
AB  - We examined whether changes in the frequency of contact with the social network
      (partner, children, grandchildren, other relatives, friends and colleagues) in a
      group of colorectal cancer patients were associated with survival. The study was
      based on a questionnaire survey from 1991. The study population consisted of 770
      Danish colorectal cancer patients diagnosed in the period 1985-1990, and followed
      up for survival until March 2002. Using Cox regression analysis we found a
      significantly higher mortality among patients who had lost their partner before
      the operation compared to patients cohabiting with the same partner as before the
      operation (rate ratio (RR)=1.4, 95% confidence interval (CI): 1.1-1.8) possibly
      because of less active cancer treatment. This needs investigation in future
      studies. Contrary to expectations we also found a significantly higher mortality
      among patients reporting increased contact with their children compared to
      patients reporting unchanged contact frequency (RR=1.7, 95% CI: 1.3-2.4).
      However, a low physical functioning of the cancer patient may have confounded the
      latter result.

PMID- 17008093
TI  - Safety and efficacy of once-per-cycle pegfilgrastim in support of ABVD
      chemotherapy in patients with Hodgkin lymphoma.
AB  - The objective of this prospective study was to examine the safety and efficacy of
      pegfilgrastim in support of chemotherapy regimens that are administered every 14
      d. Patients with Hodgkin lymphoma receiving standard ABVD (doxorubicin,
      bleomycin, vinblastine, and decarbazine) chemotherapy every 14 d were eligible
      for the study. All patients received one fixed dose of 6 mg pegfilgrastim
      approximately 24h after each ABVD infusion. Absolute neutrophil counts (ANCs)
      were measured weekly while on therapy. After completion of therapy, ANCs were
      measured every 3-4 months for 2 years, and every 6 months thereafter. Twenty
      three patients received 115 courses (230 doses) of ABVD. Nadir ANC below 0.5 x
      10(9)/L was observed only in two cases (1.1%), and ANC counts on the day of ABVD
      therapy below 1 x 10(9)/L was observed only once (0.4%). No neutropenic fever was
      observed. Two hundred and fifteen (93.5%) doses of ABVD were given on time as
      scheduled. Grade 3/4 bone pain was observed after 0.4% of ABVD doses, and
      bleomycin lung toxicity was observed in two patients. With a median follow-up of
      29 months after completion of ABVD, no myelodysplastic syndrome was observed. Two
      patients relapsed and subsequently underwent successful stem cell collection and
      transplantation. Pegfilgrastim was found to be safe in support of ABVD
      chemotherapy that is administered every 14 d. Pegfilgrastim was also effective in
      maintaining ABVD dose intensity, and keeping planned dose of chemotherapy on
      schedule.

PMID- 17008094
TI  - Health technology assessment in cancer: a personal view from public health.
AB  - Health technology assessment (HTA) poses three main questions: does it work? at
      what cost? is it worth it? Since funds for health care are always finite, it will
      not be possible to provide every form of care that may do some good for some
      people. Hard choices have to be made. HTA is a form of policy analysis that helps
      decide what to fund and what not to fund. Tensions arise mainly when a new
      intervention is clinically effective but not cost-effective, usually because the
      benefit is small and the cost high.

PMID- 17008095
TI  - Economic evaluation of cancer therapies: more and better studies will lead to
      better choices in cancer care.
AB  - Randomised phase III trials are the ideal setting for prospective collection of
      economic and health related quality of life (HRQL) data. Many studies combine
      prospective clinical data with economic assumptions or data collected in separate
      costing studies. To extrapolate the trial outcomes to lifelong consequences,
      modelling approaches are often used. Also, in situations where no randomised
      trial data are available, modelling approaches are often applied. In this paper
      some methodological and practical issues are described. The aim of the economic
      evaluations is to support decision-making. As many new promising anti cancer
      drugs are forthcoming, the questions of how decision-makers will use the results
      of the economic evaluations and how patients can optimally benefit from these new
      drugs arise.

PMID- 17008097
TI  - What's diving got to do with it?

PMID- 17008096
TI  - Evaluation of a upflow anaerobic sludge blanket reactor with partial
      recirculation of effluent used to treat wastewaters from pulp and paper plants.
AB  - The main purpose of this study was to evaluate the performance of a UASB reactor
      treating diluted black liquor from a Kraft pulp mill, which simulates an
      unbleached Kraft plant wastewater, under different operational conditions,
      including partial recycling of the effluent. The reactor's performance was
      evaluated from the standpoint of COD, pH, volatile acid concentration,
      alkalinity, concentration of methane in the biogas, and microbiological
      examinations of the sludge. Without recirculation the reduction of the HRT from
      36 to 30h did not significantly affect the average COD removal efficiency. The
      parameter displaying the greatest variation was the average concentration of
      effluent volatile acids, which increased by 16%. With recirculation the reduction
      of the HRT from 30 to 24h increased the average COD removal efficiency from 75%
      to 78%. In this case, the average effluent alkalinity also showed an increase.
      The use of partial recirculation of the effluent did not improve significantly
      the COD removal under the operational conditions tested in this work, but it was
      possible to operate the reactor with lower hydraulic retention time without
      disintegration of the granules.

PMID- 17008098
TI  - The effect of serial casting on gait in children with cerebral palsy: preliminary
      results from a crossover trial.
AB  - Serial casting aims to improve an equinus gait pattern in children with spastic
      cerebral palsy (SCP). We evaluated the effect of short-term stretch casting on
      gait in children with SCP, compared to the natural history. A crossover trial,
      consisting of a control phase and a casting phase, was conducted with children
      randomised into two groups. Both groups were assessed clinically, and using 3D
      gait analysis, at 0, 5 and 12 weeks. Subjects in one group had the 3 month
      casting phase first and in the other had the 3 month control period first. Casts
      were changed weekly and set at maximum available ankle dorsiflexion. The mean
      changes at 5 weeks and 12 weeks from baseline measurements in the casting phase
      were compared with the change within the same time interval in the control phase.
      Significant improvements in passive ankle dorsiflexion (knee flexed) were found
      at 5 and 12 weeks. Passive ankle dorsiflexion (knee extended), ankle dorsiflexion
      in single support, ankle dorsiflexion in swing and minimum hip flexion in stance
      improved significantly at 5 weeks but not at 12 weeks from baseline. Other
      kinematic parameters, the score on the Gillette Functional Assessment
      Questionnaire, and maximum reported walking distance were not changed by casting.
      Casting to improve range appears to improve passive and dynamic ankle
      dorsiflexion, but the changes are small, short lived and do not appear to affect
      function.

PMID- 17008099
TI  - Microbial rhodopsins: functional versatility and genetic mobility.
AB  - The type 1 (microbial) rhodopsins are a diverse group of photochemically reactive
      proteins that span the three domains of life. Their broad phylogenetic
      distribution has motivated conjecture that rhodopsin-like functionality was
      present in the last common ancestor of all life. Here, we discuss the evolution
      of the type 1 microbial rhodopsins and document five cases of lateral gene
      transfer (LGT) between domains. We suggest that, thanks to the functional
      versatility of these retinylidene proteins and the relative ease with which they
      can complement the existing energy-generating or photosensory repertoires of many
      organisms, LGT is in fact the principal force that determines their broad but
      patchy distribution.

PMID- 17008100
TI  - Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[omega
      (benzylmethylamino)alkoxy]xanthen-9-ones.
AB  - In this work, we further investigated a previously introduced class of
      cholinesterase inhibitors. The removal of the carbamic function from the lead
      compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new
      3-[omega-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed,
      synthesized, and evaluated for their inhibitory activity against both
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the
      alkoxy chain of compound 3 was increased and different substituents were
      introduced. From the IC(50) values, it clearly appears that the carbamic residue
      is crucial to obtain highly potent AChE inhibitors. On the other hand,
      peculiarity of these compounds is the high selectivity toward BuChE with respect
      to AChE, being compound 12 the most selective one (6000-fold). The development of
      selective BuChE inhibitors may be of great interest to clarify the physiological
      role of this enzyme and to provide novel therapeutics for various diseases.

PMID- 17008101
TI  - Design, synthesis and preliminary evaluation of new cinnamoyl pyrrolidine
      derivatives as potent gelatinase inhibitors.
AB  - A series of new cinnamoyl pyrrolidine derivatives have been synthesized based on
      the l-hydroxyproline scaffold and inhibiting activities on gelatinase (MMP-2 and 
      9) and APN were tested. Structure-activity relationship studies showed that the
      side chain with aromatic ring at C4 in pyrrolidine ring showed better inhibitory
      activities on gelatinase than aliphatic side chain. Most compounds exhibited poor
      activities on APN compared with MMP-2. Within this series, three compounds, A8,
      B9 and C10, have the good potency (IC(50)=5.2-9.7nM) and could be used as lead
      compounds in the future.

PMID- 17008102
TI  - Synthesis and evaluation of peptidic irreversible inhibitors of tissue
      transglutaminase.
AB  - Herein we report the synthesis and the evaluation of eight novel compounds as
      irreversible inhibitors of transglutaminase (TGase). These compounds are based on
      a minimal peptidic scaffold shown previously [Chem. Biol.2005, 12, 469-475] to
      confer affinity for the TGase active site and bear electrophilic groups such as
      alpha,beta-unsaturated amide, chloroacetamide or maleimide; their general
      structure being Cbz-Phe-spacer-electrophile. The affinity conferred by the Cbz
      Phe scaffold was determined by comparison to N-propylacrylamide and the length of
      the spacer was also varied to evaluate its importance. The inhibitory
      efficiencies (k(inact)/K(I)) of these compounds vary up to 10(5)M(-1)min(-1),
      among the highest reported for derivatives based on this simple Cbz-Phe peptidic
      scaffold.

PMID- 17008103
TI  - Microwave-assisted, one-pot syntheses and fungicidal activity of polyfluorinated
      2-benzylthiobenzothiazoles.
AB  - Polyfluorinated 2-benzylthiobenzothiazoles 3a-l are prepared via a microwave
      assisted, one-pot procedure. The advantages, such as good to excellent yields,
      shorter reaction time (14-21min), readily available starting material, and simple
      purification procedure, distinguish the present protocol from other existing
      methods used for the synthesis of 2-benzylthiobenzothiazoles. Bioassay indicated
      that most of the compounds showed significant fungicidal activity against
      Rhizoctonia solani, Botrytis cinereapers, and Dothiorella gregaria at a dosage of
      50microg/mL. Interestingly, compared to the control of commercial fungicide,
      triadimefon, compound 3c exhibited much higher activities against R. solani, B.
      cinereapers, and D. gregaria, which showed that the polyfluorinated 2
      benzylthiobenzothiazoles can be used as lead compound for developing novel
      fungicides.

PMID- 17008104
TI  - Synthesis and biological evaluation of a cyclic ether fluorinated noscapine
      analog.
AB  - We present here a novel semi-synthetic cyclic ether fluorinated noscapine analog
      (CEFNA) that shows potent antiproliferative and anticancer activity in both
      hormone-responsive (MCF-7) and hormone non-responsive (MDA-MB-231) breast cancer
      cells. Interestingly, it is also effective against MCF-7/Adr, an adriamycin
      resistant variant of MCF-7 cells. Immunofluorescence experiments showed numerous
      micronuclei, indicative of apoptotic cell death triggered by this novel analog.
      Mechanistically, CEFNA exerts a strong antimitotic effect as revealed by cell
      cycle studies that show a dose-dependent increase in G2/M population preceding a
      rising sub-G1 population, suggesting apoptosis.

PMID- 17008105
TI  - A new morphology of copper 7,7,8,8-tetracyano-p-quinodimethane.
AB  - Morphology control is a long-standing problem that needs to be solved for making
      the switching mechanism of copper 7,7,8,8-tetracyano-p-quinodimethane (CuTCNQ)
      understood all the time, but up till now how many morphologies CuTCNQ possesses
      and which morphology should be responsible for the on/off switching phenomenon
      are still unclear. A new morphology of CuTCNQ, namely the tubular structure, has
      been obtained and characterized in our experiment, whose formation mechanism has
      also been investigated. Through characterizing, we can conclude that the tubular
      structure belongs to the phase I, which can be further confirmed by the
      electrical measurements. From the I-V plots, the carrier mobility of the tubular
      structure is estimated to be approximately 0.1 cm2 V-1 s-1, which suggests the
      potential application of CuTCNQ in devices.

PMID- 17008106
TI  - The effect of estrogen and progesterone on spreading depression in rat
      neocortical tissues.
AB  - Although gender differences in the incidence of migraine with aura appear to be
      related to high circulating levels of ovarian hormones, the underlying mechanisms
      are not yet fully understood. Several studies have suggested a major role for
      spreading depression (SD) in the pathogenesis and symptomatology of migraine with
      aura. To investigate a possible role of SD in the association of high female
      hormones and attacks of migraine with aura, the effects of beta-estradiol and
      progesterone on SD were studied in rat neocortical tissues. Application of both
      hormones enhanced the repetition rate as well as the amplitude of SD in
      neocortical slices treated with hypotonic artificial cerebrospinal fluid. beta
      Estradiol and progesterone also dose dependently increased the amplitude of SD
      induced by KCl microinjection. Both hormones exhibited a pronounced, persisting,
      and significant enhancement of long-term potentiation of the field excitatory
      postsynaptic potential in the neocortical tissues. The changes in SD
      characteristics in the presence of estrogen and progesterone may responsible for
      increased migraine with aura attacks associated by high female hormones. These
      hormones may exert their effects on SD via facilitation of synaptic transmission.

PMID- 17008108
TI  - Neuronal neprilysin overexpression is associated with attenuation of Abeta
      related spatial memory deficit.
AB  - Converging evidence links abnormally high brain concentrations of amyloid-beta
      peptides (Abeta) to the pathology of Alzheimer's disease (AD). Lowering brain
      Abeta levels, therefore, is a therapeutic strategy for the treatment of AD.
      Neuronal neprilysin upregulation led to increased degradation of Abeta, reduced
      the formation of Abeta-plaques and the associated cytopathology, but whether
      overexpression of neprilysin can improve cognition is unknown. We show that
      neuronal overexpression of neprilysin improved the Morris water maze memory
      performance in mice with memory deficits resulting from overexpression of the AD
      causing mutated human amyloid precursor protein (APP). This improvement was
      associated with decreased brain levels of Abeta and with unchanged
      endoproteolytic processing of APP. These results provide the evidence that
      lowering of brain Abeta levels by increasing its degradation can improve
      cognitive functions in vivo, and suggest that increasing the activity of
      neprilysin in brain may be effective in preventing cognitive decline in AD.

PMID- 17008107
TI  - Signal transducers and activators of transcription 5 contributes to
      erythropoietin-mediated neuroprotection against hippocampal neuronal death after
      transient global cerebral ischemia.
AB  - The signal transducers and activators of transcription (STAT) proteins are a
      group of transcriptional factors. Among them, STAT5 initiates a pro-survival
      signaling cascade. So far, little has been known about the role of STAT5 in
      cerebral ischemia and reperfusion. This study examines the phosphorylation status
      of STAT5 in hippocampal CA1 in the early stage after transient global cerebral
      ischemia in rats. Our data show that the phosphorylation of STAT5 was increased
      in hippocampal CA1 at 1h and 3h ischemia. Taking advantage of the neuroprotective
      effect of erythropoietin (EPO) in CA1, we further demonstrated that the
      administration of EPO enhanced the phosphorylation of STAT5, with SATA5a being
      phosphorylated earlier. The enhanced phosphorylation of STAT5 in the EPO-treated
      group was accompanied by the upregulation of STAT5 downstream gene products, Bcl
      xL and XIAP. Consequently, ischemic CA1 neuronal damage was attenuated by the
      administration of EPO. Both the enhancement of STAT5 phosphorylation and the
      neuroprotection rendered by EPO were blocked by Tyrphostin, a selective inhibitor
      for Janus kinase 2, which is an upstream kinase of STAT5. These findings suggest
      an association between the activation of STAT5 and CA1 neuronal survival after
      cerebral ischemia.

PMID- 17008109
TI  - Surgical treatment of chronic atrial fibrillation combined with rheumatic mitral
      valve disease: Effects of the cryo-maze procedure and predictors for late
      recurrence.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of the modified maze
      procedure using cryoablation for treating chronic atrial fibrillation (AF)
      associated with rheumatic mitral valve disease and to assess the risk factors for
      late failure of sinus rhythm restoration. METHODS: Between March 2000 and June
      2004, 170 consecutive patients, who underwent the modified maze procedure using
      cryoablation concomitant with mitral valve surgery for atrial fibrillation
      associated with rheumatic mitral valve disease, were divided into two groups
      based on the type of right-sided maze: the modified Cox-maze III (CM group, n=93)
      and modified Kosakai-maze (KM group, n = 77) procedures. The postoperative and
      mid-term follow-up results were analyzed and compared between the two groups.
      Both univariate and multivariate analyses were used to assess the risk factors
      for late recurrence of atrial fibrillation. RESULTS: There were three in-hospital
      deaths, including two in the CM group (2.2%) and one in the KM group (1.3%), and
      there were no significant differences in the incidence of postoperative
      complications between the two groups. The cardiopulmonary bypass and aortic cross
      clamp times were significantly shorter in the KM group than the CM group. At
      discharge, the sinus rhythm rate was 70% in the CM group and 74% in the KM group
      (p = 0.55). Follow-up was completed in 97% of the patients, with a mean time of
      26.6+/-15.2 months. At the latest follow-up, one death occurred in the CM group
      (0.6%). Sinus rhythm was documented in 141 (84%) out of all the patients,
      including 76 (84%) in the CM group and 65 (86%) in the KM group (p=0.72). The 4
      year actuarial survival free from stroke was 90.3+/-5.9% for the CM group and
      96.4+/-3.5% for the KM group (p = 0.68), and 4-year event-free survival was
      81.2+/-7.4% for the CM group and 96.4+/-3.5% for the KM group (p = 0.078). Using
      a multivariate analysis, a left atrial dimension >65 mm (p = 0.011) and repair
      for rheumatic mitral valve disease (p = 0.038) were independent risk factors for
      a late recurrence of AF. CONCLUSIONS: The modified maze procedures using
      cryoablation are safe and effective in treating chronic atrial fibrillation
      associated with rheumatic mitral valve disease.

PMID- 17008110
TI  - Decreased nerve growth factor levels in hyperthyroid Graves' ophthalmopathy
      highlighting the role of neuroprotective factor in autoimmune thyroid diseases.
AB  - Nerve growth factor (NGF), which is a neurotrophic factor, is involved in
      autoimmune and inflammatory processes. Serum NGF levels were investigated in 131
      patients with autoimmune (95 with Graves' disease, of whom 57 had ophthalmopathy,
      19 with Hashimoto's thyroiditis) and nonimmune thyroid diseases (17 with toxic
      nodular goitre), and 20 controls. NGF levels were measured via enzyme-linked
      immunosorbent assay. Twenty-nine positive cases for NGF were detected: 21 cases
      in Graves' disease, 7 cases in Hashimoto's thyroiditis, no case in toxic nodular
      goitre and one case in controls. NGF levels were higher in patients with Graves'
      disease and particularly with Hashimoto's thyroiditis compared with controls
      (1786.47+/-34.79 pg/ml and 1996.27+/-77.71pg/ml vs 1579.16+/-57.45pg/ml, P<0.049
      and P<0.0001, respectively). Increased NGF levels associated with Graves'
      hyperthyroidism and correlated with FT(3) (P<0.01). Patients with the presence of
      antibodies against TSH receptor showed higher NGF levels than those with no
      antibodies (1938.61+/-56.44pg/ml vs 1712.12+/-54.22pg/ml, P<0.009). Decreased NGF
      levels were demonstrated in hyperthyroid Graves' ophthalmopathy compared with
      those without eye symptoms (1746.65+/-51.98pg/ml vs 1910.47+/-55.62pg/ml,
      P<0.036). NGF may be involved in the pathomechanism of autoimmune thyroid
      diseases. Decreased NGF levels in hyperthyroid Graves' ophthalmopathy highlight
      the importance of NGF in the neuroprotection of orbital tissues.

PMID- 17008111
TI  - Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient
      vascularization and subchondral bone remodeling in drilled cartilage defects.
AB  - OBJECTIVE: Marrow-stimulation techniques are used by surgeons to repair cartilage
      lesions although consistent regeneration of hyaline cartilage is rare. We have
      shown previously that autologous blood can be mixed with a polymer solution
      containing chitosan in a glycerol phosphate (GP) buffer (chitosan-GP), and that
      implantation of this polymer/blood composite onto marrow-stimulated chondral
      defects in rabbit and sheep leads to the synthesis of more chondral repair tissue
      with greater hyaline character compared to marrow-stimulation alone. In the
      current study, we examined the modulation of cell recruitment and repair tissue
      characteristics at early post-surgical time points (from day 1 to 56) in a rabbit
      model to elucidate potential mechanisms behind this improved repair outcome.
      DESIGN: Thirty-three skeletally mature New Zealand White rabbits underwent
      bilateral arthrotomies, with each trochlea receiving a cartilage defect (3.5 mm x
      4.5mm) bearing four microdrill holes (0.9 mm diameter, approximately 4 mm deep)
      into the subchondral bone. One defect per rabbit was treated with a chitosan
      GP/blood implant, while the other defect was left as a microdrilled control.
      Repair tissues were stained by histochemistry, for collagen types I, II, and X by
      immunohistochemistry and analyzed using quantitative stereological tools.
      RESULTS: Histological analyses demonstrated that control defects followed a
      typical healing sequence observed previously in marrow-stimulation animal models
      while chitosan-GP/blood implants led to three significant modifications in the
      healing sequence at early stages: (1) increased inflammatory and marrow-derived
      stromal cell recruitment to the microdrill holes, (2) increased vascularization
      of the provisional repair tissue in the microdrill holes, and (3) increased
      intramembranous bone formation and subchondral bone remodeling (BR). CONCLUSIONS:
      These results suggest that the greater levels of provisional tissue
      vascularization and BR activity are main factors supporting improved cartilage
      repair when chitosan-GP/blood implants are applied to marrow-stimulated cartilage
      lesions.

PMID- 17008112
TI  - Double-quantum filtered rotational-echo double resonance.
AB  - The homonuclear scalar coupling of a directly bonded 13C-13C pair has been used
      to create a double-quantum filter (DQF) to remove the natural-abundance 13C
      background in 13C{15N} rotational-echo double-resonance (REDOR) experiments. The
      DQF scalar and REDOR dipolar evolution periods are coincident which is important
      for sensitivity in the event of weak 13C-15N dipolar coupling. Calculated and
      observed 13C{15N} DQF-REDOR dephasings were in agreement for a test sample of
      mixed recrystallized labeled alanines. Glycine metabolism in a single uniform-15N
      soybean leaf labeled for 6 min by 13CO2 was measured quantitatively by 13C{15N}
      DQF-REDOR with no background interferences.

PMID- 17008113
TI  - Redistribution of carbon flux in Torulopsis glabrata by altering vitamin and
      calcium level.
AB  - Manipulation of cofactor (thiamine, biotin and Ca(2+)) levels as a potential tool
      to redistribute carbon flux was studied in Torulopsis glabrata. With sub
      optimization of vitamin in fermentation medium, the carbon flux was blocked at
      the key node of pyruvate, and 69 g/L pyruvate was accumulated. Increasing the
      concentrations of thiamine and biotin could selectively open the valve of carbon
      flux from pyruvate to pyruvate dehydrogenase complex, the pyruvate carboxylase
      (PC) pathway and the channel into the TCA cycle, leading to the over-production
      of alpha-ketoglutarate. In addition, the activity of PC was enhanced with Ca(2+)
      present in fermentation medium. By combining high concentration's vitamins and
      CaCO(3) as the pH buffer, a batch culture was conducted in a 7-L fermentor, with
      the pyruvate concentration decreased to 21.8 g/L while alpha-ketoglutarate
      concentration increased to 43.7 g/L. Our study indicated that the metabolic flux
      could be redistributed to overproduce desired metabolites with manipulating the
      cofactor levels. Furthermore, the manipulation of vitamin level provided an
      alternative tool to realize metabolic engineering goals.

PMID- 17008114
TI  - Cytosolic NADPH metabolism in penicillin-G producing and non-producing chemostat
      cultures of Penicillium chrysogenum.
AB  - This study addresses the relation between NADPH supply and penicillin synthesis,
      by comparing the flux through the oxidative branch of the pentose phosphate
      pathway (PPP; the main source of cytosolic NADPH) in penicillin-G producing and
      non-producing chemostat cultures of Penicillium chrysogenum. The fluxes through
      the oxidative part of the PPP were determined using the recently introduced
      gluconate-tracer method. Significantly higher oxidative PPP fluxes were observed
      in penicillin-G producing chemostat cultures, indicating that penicillin
      production puts a major burden on the supply of cytosolic NADPH. To our knowledge
      this is the first time direct experimental proof is presented for the causal
      relationship between penicillin production and NADPH supply. Additional insight
      in the metabolism of P. chrysogenum was obtained by comparing the PPP fluxes from
      the gluconate-tracer experiment to oxidative PPP fluxes derived via metabolic
      flux analysis, using different assumptions for the stoichiometry of NADPH
      consumption and production.

PMID- 17008115
TI  - Tyrosinemia type I treated by NTBC: how does AFP predict liver cancer?
AB  - BACKGROUND: Tyrosinemia type I is associated with an increased risk of liver
      cancer development. The formation of the pathogenic fumarylacetoacetate is
      prevented by 2-(2-nitro-4-3 trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC).
      Still, some patients with NTBC treatment develop liver cancer. A rise of alpha
      fetoprotein (AFP) is an indicator of liver cancer. AIM: To study the predictive
      value of AFP in tyrosinemia type I patients for the discrimination between
      patients at high and low risk of liver cancer development. METHODS: We examined
      the course of AFP values of 11 Dutch patients with tyrosinemia type I treated by
      NTBC, of whom four were diagnosed with liver cancer. RESULTS: The four patients
      with liver cancer had a course of AFP different from the other patients in either
      velocity of the decrease of AFP, achieving normal AFP and/or having a rise of AFP
      concentrations. CONCLUSION: Apart from a rise of AFP, a slow AFP decrease, and
      never normalizing levels of AFP are important predictors of liver cancer
      development in further life.

PMID- 17008116
TI  - Impact of a CART promoter genetic variation on plasma lipid profile in a general
      population.
AB  - The cocaine and amphetamine regulated transcript (CART), an anorexigenic peptide
      responding to leptin, is expressed in various areas of the hypothalamus. The role
      of CART in humans and its potential contribution to abnormalities in feeding
      control are mostly unknown. Since CART plays an important role in the
      hypothalamic regulation of energy balance by reducing food intake and increasing
      lipid substrate utilization, it might affect cholesterol metabolism as
      Neuropeptide Y or pro-opiomelanocortin do. In the present work, we studied the
      potential effects of three SNPs of the CART promoter in a WHO-MONICA general
      population from North of France (n=840), untreated for hypercholesterolemia,
      hypertension, or diabetes mellitus since any treatment is likely to interfere
      with lipoprotein/lipid variables. Our results show associations between these
      SNPs and plasma LDL-cholesterol level and the LDL/HDL ratio, a marker of
      atherogenicity. A haplotypic study suggests that these effects are mainly
      attributable to the functional SNP -3608C>T. Subjects bearing the -3608 C allele
      present a plasma lipid profile protective against atherogenesis: decrease of
      plasma LDL-cholesterol level (p=0.001) and of the LDL/HDL ratio (p=0.0003). This
      result offers new evidences for a potential implication of the CART gene in lipid
      metabolism and in atherogenesis.

PMID- 17008117
TI  - The effect of solution level on calorific and dosimetric results in a 70 kHz
      tower type sonochemical reactor.
AB  - In order to design and optimise sonochemical reactors it is important to study
      the impact of liquid level, or path length, on the standing wave phenomena and
      the influence this has on temperature increase and OH radical rate of production.
      In this work, an ultrasonic tower type reactor operating at 70 kHz is
      investigated with results from variations to liquid levels reported. Calorimetry
      data was obtained using a modified reactor set up with temperature change
      monitored at selected points within the chamber. OH radical rate of formation was
      shown via chemical dosimetry, following the conversion of terephthalic acid (TA)
      to 2-hydroxyterephthalic acid (HTA). The results obtained have shown that changes
      in solution depth of a few millimetres significantly impacts on the interaction
      of the propagated and reflected waveforms with the results of calorific
      measurements and HTA rates of formation varying by 90% (750 J) and 88% (80 mmol
      dm(-3) min(-1)) between the operational extremes over the studied depth range.

PMID- 17008118
TI  - A role for WASP Interacting Protein, WIP, in fibroblast adhesion, spreading and
      migration.
AB  - The WASP (Wiskott Aldrich Syndrome Protein) Interacting Protein, WIP, regulates
      actin polymerization and the formation of actin-rich structures such as filopodia
      and lamellipodia, each of which is involved in cellular adhesion, spreading and
      migration. To define the role for WIP in these activities, we analysed cell
      adhesion and spreading as well as the redistribution of polymerised actin and
      paxillin that occurred when fibroblasts were plated onto different substrata. We
      compared the effect of WIP overexpression (gain of function) with that of WIP
      deficiency (loss of function) on these parameters. WIP-overexpression delayed
      cellular adhesion and spreading, an effect that could be compensated for by
      exposure to Y-27632, a well characterized ROCK (Rho kinase) inhibitor. WIP
      overexpression augmented the phosphorylation of Erk and JNK induced by binding to
      fibronectin, suggesting that WIP participates in signal transduction pathways
      initiated by integrin engagement. Conversely, WIP deficiency accelerated
      fibroblast adhesion to plastic and led to the formation of enlarged focal
      adhesions. The influence of WIP on fibroblast migration was measured by scratch
      assay. WIP-overexpression reduced migration while WIP-deficiency increased it,
      suggesting that WIP acts as a negative regulator of fibroblast migration.
      Together, these findings suggest a novel role for WIP in fibroblast adhesion,
      spreading and migration.

PMID- 17008119
TI  - Bacillus anthracis: a multi-faceted role for anthrax lethal toxin in thwarting
      host immune defenses.
AB  - Lethal factor (LF), along with its receptor-binding partner protective antigen
      (PA), forms lethal toxin (LT), a critical virulence factor for Bacillus
      anthracis. LF is a Zn(2+) protease that cleaves specific mitogen activated
      protein kinase kinases (MAPKKs), inactivating signal transduction intermediates
      required for normal immune function. Initial research emphasized the role of LT
      in attenuating pro-inflammatory responses by macrophages, the primary targets of
      infection. More recent studies have revealed that LT affects a broad range of
      immune cells. In addition to direct effects on macrophages and neutrophils, LT
      suppresses the costimulatory functions of dendritic cells, thereby impeding
      essential cross-talk between innate and adaptive immune responses. Moreover, LT
      acts directly on T and B lymphocytes, blocking antigen receptor-dependent
      proliferation, cytokine production and Ig production. In this manner, LT mounts a
      broad-based attack on host immunity, thus providing B. anthracis with multiple
      mechanisms for avoiding protective host responses.

PMID- 17008120
TI  - Recent surprises in protein targeting to mitochondria and plastids.
AB  - The functions of mitochondria and chloroplasts rely on thousands of proteins,
      mostly imported from the cytosol through specialized import channels. Neither the
      detailed import mechanisms nor the identities of all targeted proteins are known.
      Recent surprises include unexpected results concerning import receptors,
      unexpectedly frequent dual-targeting of proteins, and the discovery of novel
      routes of protein trafficking. Such findings make it more difficult to predict
      which proteins really are targeted to organelles. By combining experimental and
      bioinformatics data, we estimate the size of the mitochondrial and plastid
      proteomes to be approximately 2000 and 2700 proteins, respectively. Advances in
      cell and organelle fractionation coupled with modern proteomics techniques are
      probably the best route to understanding organellar protein composition.

PMID- 17008121
TI  - Endomembrane proton pumps: connecting membrane and vesicle transport.
AB  - pH-homeostasis in the endomembrane system requires the activity of proton-pumps.
      In animals, the progressive acidification of compartments along the endocytic and
      secretory pathways is critical for protein sorting and vesicle trafficking, and
      is achieved by the activity of the vacuolar H(+)-ATPase (V-ATPase). Plants have
      an additional endomembrane pump, the vacuolar H(+)-pyrophosphatase (V-PPase), and
      previous research was largely focused on the respective functions of the two
      pumps in secondary active transport across the tonoplast. Recent approaches,
      including reverse genetics, have not only provided evidence that both enzymes
      play unique and essential roles but have also highlighted the important functions
      of the two proton pumps in endocytic and secretory trafficking.

PMID- 17008123
TI  - Herd protection against influenza.
AB  - Mortality and hospitalization rates due to influenza have risen despite
      increasing vaccine coverage for the most vulnerable population; however, those
      most vulnerable to complications and death are the least likely to respond to the
      vaccine. New strategies for influenza control are needed and indirect
      effectiveness (herd protection) has been demonstrated for several currently used
      vaccines - rubella, H. influenzae type b, pneumococcus varicella and hepatitis A.
      The Japanese schoolchildren program provided proof of concept of indirect
      effectiveness of influenza vaccine. The Central Texas field trial has
      demonstrated significant herd protection of adults utilizing the live, attenuated
      influenza vaccine (LAIV) to children. Immunization of <20% of children at the
      intervention site resulted in an 8-18% reduction of medically attended acute
      respiratory illness in adults compared to rates in the comparison sites. LAIV
      given by nasal spray is efficacious against matched and poorly matched prevalent
      strains, easy to administer and readily accepted by children for annual
      immunization. School-based clinics could provide a platform for rapid deployment
      of vaccine accessible to all segments of the population. This strategy could be
      critical for control of pandemic influenza.

PMID- 17008122
TI  - Multi-year study of human metapneumovirus infection at a large US Midwestern
      Medical Referral Center.
AB  - BACKGROUND: Because of its recent identification, few multi-year epidemiologic
      studies of hMPV infection have been reported. OBJECTIVE: We sought to
      retrospectively describe hMPV infections among patients evaluated by a large US
      Midwestern referral laboratory. STUDY DESIGN: Clinical specimens were submitted
      to a large US Midwest referral hospital from 1 October 2001 to 18 May 2004. RT
      PCR was used to retrospectively screen the clinical specimens for human
      metapneumovirus. Demographic and clinical data were retrieved. RESULTS: 34 (2.6%)
      of 1294 specimens were hMPV positive. Among these, 21 (62%) were culture positive
      and available for genetic typing. A previously considered rare genotype of hMPV,
      B1, was the most common single genotype identified, comprising 9 (43%) of the 21
      isolates. Multivariate logistic regression modeling identified patients aged 0.4
      9 years (OR=8.9; 95% CI=2.0-38.5) and those under intensive care (OR=3.2; 95%
      CI=1.1-8.7) as more likely to have hMPV infection than their peers. CONCLUSION:
      In this large referral hospital viral assays more often had evidence of hMPV when
      they were collected from children receiving intensive care.

PMID- 17008124
TI  - The silent period of the thenar muscles to contralateral and ipsilateral deep
      brain stimulation.
AB  - OBJECTIVE: We aimed at characterizing the silent period induced in hand muscles
      by subcortical stimulation through electrodes implanted on the subthalamic
      nucleus for deep brain stimulation (STN-DBS). METHODS: In 10 patients with
      Parkinson's disease, we analyzed the inhibitory effects induced in the
      contralateral and ipsilateral thenar muscles by STN-DBS of varying stimulus
      intensity and strength of muscle contraction. RESULTS: Both, the contralateral
      silent period (CSP) and the ipsilateral silent period (ISP) were induced by
      stimuli at an intensity subthreshold for eliciting a contralateral motor evoked
      potential (MEP) and were composed of two phases. With a stimulus intensity of
      120% of active threshold and a strength of 20%, the first CSP had a mean onset
      latency of 38.0 +/- 2.9 ms and a mean duration of 37.7 ms +/- 2.8 ms, and the
      second CSP had a mean onset latency of 90.6 +/- 18.5 ms and a mean duration of
      53.4 +/- 6.3 ms. The first ISP had a mean onset latency of 34.9 +/- 4.3 ms and a
      mean duration of 12.5 +/- 3.4 ms, and the second ISP had a mean onset latency of
      76.3 +/- 10.1 ms and a mean duration of 23.1 +/- 9.0 ms. The duration of both
      phases of the CSP increased with increasing the stimulus intensity and the burst
      separating the two phases of the CSP increased in size with increasing the
      strength of muscle contraction or the stimulus intensity. No ipsilateral MEP was
      observed in any patient at any strength or stimulus intensity. CONCLUSION: Our
      results indicate that the silent period induced by STN-DBS has specific
      physiological mechanisms that differ from those of the silent period induced by
      cortical transcranial magnetic stimulation. SIGNIFICANCE: The induction of ISP by
      stimulation of the motor tract at a point caudal to the corpus callosum indicates
      that non-callosal pathways are capable of generating ISP.

PMID- 17008126
TI  - Clinical neurophysiology of language: the MEG approach.
AB  - Clinical evaluation of language function and basic neuroscience research into the
      neurophysiology of language are tied together. Whole-head MEG systems readily
      facilitate detailed spatiotemporal characterization of language processes. A fair
      amount of information is available about the cortical sequence of word perception
      and comprehension in the auditory and visual domain, which can be applied for
      clinical use. Language production remains, at present, somewhat less well
      charted. In clinical practice, the most obvious needs are noninvasive evaluation
      of the language-dominant hemisphere and mapping of areas involved in language
      performance to assist surgery. Multiple experimental designs and analysis
      approaches have been proposed for estimation of language lateralization. Some of
      them have been compared with the invasive Wada test and need to be tested
      further. Development of approaches for more comprehensive pre-surgical
      characterization of language cortex should build on basic neuroscience research,
      making use of parametric designs that allow functional mapping. Studies of the
      neural basis of developmental and acquired language disorders, such as dyslexia,
      stuttering, and aphasia can currently be regarded more as clinical or basic
      neuroscience research rather than as clinical routine. Such investigations may
      eventually provide tools for development of individually targeted training
      procedures and their objective evaluation.

PMID- 17008125
TI  - Gamma and beta neural activity evoked during a sensory gating paradigm: effects
      of auditory, somatosensory and cross-modal stimulation.
AB  - OBJECTIVE: Stimulus-driven salience is determined involuntarily, and by the
      physical properties of a stimulus. It has recently been theorized that neural
      coding of this variable involves oscillatory activity within cortical neuron
      populations at beta frequencies. This was tested here through experimental
      manipulation of inter-stimulus interval (ISI). METHODS: Non-invasive
      neurophysiological measures of event-related gamma (30-50 Hz) and beta (12-20 Hz)
      activity were estimated from scalp-recorded evoked potentials. Stimuli were
      presented in a standard "paired-stimulus" sensory gating paradigm, where the S1
      (conditioning) stimulus was conceptualized as long-ISI, or "high salience", and
      the S2 (test) stimulus as short-ISI, or "low salience". Three separate studies
      were conducted: auditory stimuli only (N = 20 participants), somatosensory
      stimuli only (N = 20), and a cross-modal study for which auditory and
      somatosensory stimuli were mixed (N = 40). RESULTS: Early (20-150 ms) stimulus
      evoked beta activity was more sensitive to ISI than temporally-overlapping gamma
      band activity, and this effect was seen in both auditory and somatosensory
      studies. In the cross-modal study, beta activity was significantly modulated by
      the similarity (or dissimilarity) of stimuli separated by a short ISI (0.5 s); a
      significant cross-modal gating effect was nevertheless detected. CONCLUSIONS:
      With regard to the early sensory-evoked response recorded from the scalp, the
      interval between identical stimuli especially modulates beta oscillatory
      activity. SIGNIFICANCE: This is consistent with developing theories regarding the
      different roles of temporally-overlapping oscillatory activity within cortical
      neuron populations at gamma and beta frequencies, particularly the claim that the
      latter is related to stimulus-driven salience.

PMID- 17008127
TI  - Environmental factors influence the production of enterobactin, salmochelin,
      aerobactin, and yersiniabactin in Escherichia coli strain Nissle 1917.
AB  - The probiotic Escherichia coli strain Nissle 1917 produces four siderophores: the
      catecholates enterobactin and salmochelin, the hydroxamate aerobactin, and the
      mixed-type siderophore yersiniabactin. We studied the influence of pH,
      temperature, and carbon source on the production of these four siderophores.
      Yersiniabactin and salmochelin were maximally produced under neutral to alkaline
      conditions (pH 7.0 and 7.6, respectively), whereas aerobactin was maximally
      produced at a more acidic pH (pH 5.6), which agrees with the slightly higher
      complex stability of hydroxamates at acidic pH values compared to the
      catecholates. Under nearly all conditions studied, catecholate siderophore
      production was higher with glycerol than with glucose as the carbon source.
      Yersiniabactin production was also higher with glycerol as the carbon source at
      pH 7.0. At 42 degrees C, strain Nissle 1917 grew poorly or not at all because of
      the iron-limiting conditions. In a competition experiment between wild-type
      strain Nissle 1917 and a mutant of this strain with a deletion in the
      yersiniabactin operon, the wild-type overgrew the mutant at pH 7.0 and 7.6 and
      not at pH 5.6. These results agree with yersiniabactin production being of
      greater advantage at neutral and slightly alkaline pH values. The production of
      four siderophores may help the probiotic E. coli Nissle 1917 to compete with
      other E. coli strains in the colon. The probiotic strain Nissle 1917 used in our
      experiments has many characteristics in common with uropathogenic E. coli and
      other pathogenic strains which also secrete these siderophores. Uropathogenic E.
      coli strains may need the multitude of siderophores to adapt to the pH of urine,
      which varies between pH 4.6 and 8.0.

PMID- 17008128
TI  - Pesticide poisoning of farm workers-implications of blood test results from
      Vietnam.
AB  - Information on the health impacts of pesticides is quite limited in many
      developing countries, with many surveys relying solely on farmer self-assessments
      of their health status. To test the reliability of self-reported data, an acetyl
      cholinesterase enzyme (AChE) blood test was conducted for 190 rice farmers in the
      Mekong Delta, Vietnam. Results reveal a high prevalence of pesticide poisoning by
      organophosphate and carbamate exposure, where over 35% of test subjects
      experienced acute pesticide poisoning (a reduction of AChE >25%), and 21%
      chronically poisoned (>66% AChE reduction). Using the medical test results as
      benchmarks, we find that farmers' self-reported symptoms have very weak
      associations with actual poisoning. To investigate the possible determinants of
      pesticide poisoning, a probit model was constructed with pesticide amount,
      toxicity, training, and the use of protective measures as explanatory variables.
      The results indicate that although the absolute amount of pesticides used does
      not increase the probability of poisoning, a 1% increase in the use of highly
      hazardous pesticides (WHO Ia or Ib) increases the probability of poisoning by
      3.9% and an increased use of protective measures decreases the probability of
      poisoning by 44.3%. We also find significant provincial differences in poisoning
      incidence after we control for individual factors. The provincial effects
      highlight the potential importance of negative externalities, and suggest that
      future research on pesticide-related damage should include information on local
      water, air and soil contamination.

PMID- 17008129
TI  - Clustering of childhood cancer in the inner city of Tehran metropolitan area: a
      GIS-based analysis.
AB  - The aim of this study was both to map the childhood cancer incidence in the
      districts of Tehran metropolitan area and to explore possible clustering of
      cancer cases in the diverse environments of this area. All incidence cases of
      childhood cancers (age group under 15 years) belonging to the 22 districts of
      Tehran metropolis and occurring during the period of 1998 till 2002 were
      ascertained from three sources. Each case's place of residency was geo
      referenced. The scan statistics cluster detecting technique was used to evaluate
      clustering of cases throughout Tehran. The overall incidence rate (IR) of
      childhood cancer was 176.3/1,000,000 children under 15 years of age. The lowest
      IR among both boys and girls was observed in district 22 (69.4/1,000,000) and the
      highest was observed in district 6 (242.09/1,000,000). The detection of clusters
      was performed for all cancer sites. All the cancer sites combined category showed
      clustering in the districts 7, 13, 8, 6, 3, 14, 12, 11, and 4. For this category,
      the clustering likelihood was marginally statistically significant (p
      value=0.056), with an overall relative risk of 1.30. No statistically significant
      patterns of clustering were detected for other categories.

PMID- 17008130
TI  - B cell reconstitution after rituximab treatment of lymphoma recapitulates B cell
      ontogeny.
AB  - The long-term immunologic effects of B cell depletion with rituximab and the
      characteristics of the reconstituting B cell pool in lymphoma patients are not
      well defined, despite the widespread usage of this therapy. Here we report that
      during the B cell reconstitution phase a majority of the peripheral blood B cells
      have an immature transitional phenotype (47.8%+/-25.2% vs. 4.4%+/-2.4% for normal
      controls, p<0.0001), similar to what has been described during the original
      ontogeny of the immune system and following bone marrow transplantation.
      Moreover, the recovery of the CD27+ memory B cell pool was delayed compared to
      normal B cell ontogeny, remaining below normal controls at 1 year post-rituximab
      (4.4%+/-3% vs. 31%+/-7%, p<0.0001). Expansion of functionally immature B cells
      and decreased memory B cells may contribute to an immunodeficient state in
      patients recovering from rituximab mediated B cell depletion, particularly with
      repeated treatment.

PMID- 17008131
TI  - Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe
      disease.
AB  - Enzyme replacement therapy (ERT) became a reality for patients with Pompe
      disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a
      deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA).
      The therapy, which relies on receptor-mediated endocytosis of recombinant human
      GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal
      muscle. We have previously shown a profound disturbance of the lysosomal
      degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice
      (KO). Our findings here demonstrate a progressive age-dependent autophagic
      buildup in addition to enlargement of glycogen-filled lysosomes in multiple
      muscle groups in the KO. Trafficking and processing of the therapeutic enzyme
      along the endocytic pathway appear to be affected by the autophagy. Confocal
      microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA
      indicates that a significant portion of the endocytosed enzyme in the KO was
      trapped as a partially processed form in the autophagic areas instead of reaching
      its target--the lysosomes. A fluid-phase endocytic marker was similarly
      mistargeted and accumulated in vesicular structures within the autophagic areas.
      These findings may explain why ERT often falls short of reversing the disease
      process and point toward new avenues for the development of pharmacological
      intervention.

PMID- 17008132
TI  - Therapeutic angiogenesis: translating experimental concepts to medically relevant
      goals.
AB  - Angiogenesis is central to many physiological and pathological phenomena. In
      physiological angiogenesis, new vessels are well shaped and their growth is
      finely tuned to match the metabolic needs of tributary tissues. Accordingly,
      neovascularization is activated by physical exercise and destabilized by non-use.
      In contrast, pathological blood vessels that are observed in retinal
      neovascularization, cancer or in ischemic tissues are leaky, irregularly shaped,
      and tend to form arterial-venous fistulae. A great deal of attention is focused
      on new approaches for medical manipulation of vascular growth. These methods are
      aimed at facilitating the reperfusion of ischemic tissues or eradicating
      pathological vasculature. In this position paper, we challenge the rationale of
      therapeutic angiogenesis for the cure of myocardial and peripheral ischemia.
      Therapeutic angiogenesis aims at combating the insufficiency of, or insensitivity
      to angiogenic factors in the setting of atherosclerotic-induced arterial
      occlusion. However, clinical evidence indicates that such a defect is not common
      among patients with ischemic disease, as a whole. Genetic and environmental
      factors could account for the great heterogeneity in the expression of the master
      angiogenic factors. Future improvements in the strategy would require the
      introduction of in vitro assays and in vivo imaging systems for assessing human
      angiogenesis. Finally, the promise is to find individualized angiogenesis-based
      therapies for a genuine cure of ischemia and prevention of organ failure.

PMID- 17008133
TI  - Hypothyroidism: a possible risk factor for liver cancer in patients with no known
      underlying cause of liver disease.
AB  - BACKGROUND & AIMS: Up to 25% of hepatocellular carcinomas (HCCs) seen in U.S.
      centers are of unknown etiology. Animal studies suggest that hypothyroidism can
      directly cause liver cell damage and might be a risk factor for HCC. We conducted
      a case-control study to evaluate the relationship between hypothyroidism and HCC.
      METHODS: Cases (n = 54) were HCC patients seen at Mayo Clinic Rochester in whom
      no underlying etiology for chronic liver disease could be determined. Two groups
      of controls were selected, HCC patients with HCV (n = 57) and HCC patients with
      alcoholic liver disease (n = 49). Hypothyroidism was defined as thyroid
      stimulating hormone level >5.0, history of hypothyroidism before HCC diagnosis,
      or a history of being on thyroid replacement at the time of HCC diagnosis. We
      used multivariate logistic regression to model the relationship between
      hypothyroidism and HCC etiology. RESULTS: Of the 160 patients, 18 (11%) had a
      history of hypothyroidism. Twelve (22%) of those with no known etiology for HCC,
      2 (4%) of those with HCV, and 4 (8%) of those with alcoholic liver disease had
      hypothyroidism. Patients with HCC of unknown etiology were significantly more
      likely to have a history of hypothyroidism as compared with HCC patients with HCV
      (adjusted odds ratio, 12.7; 95% confidence interval, 1.4-117.1) and as compared
      with all controls (adjusted odds ratio, 6.8; 95% confidence interval, 1.1-42.1).
      CONCLUSIONS: Hypothyroidism is more prevalent in HCC patients with an unknown
      etiology. It should be further investigated as a potential risk factor in liver
      carcinogenesis.

PMID- 17008134
TI  - GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo.
AB  - JAK/STAT signaling is essential for a wide range of developmental processes in
      Drosophila melanogaster. The mechanism by which the JAK/STAT pathway contributes
      to these processes has been the subject of recent investigation. However, a
      reporter that reflects activity of the JAK/STAT pathway in all Drosophila tissues
      has not yet been developed. By placing a fragment of the Stat92E target gene
      Socs36E, which contains at least two putative Stat92E binding sites, upstream of
      GFP, we generated three constructs that can be used to monitor JAK/STAT pathway
      activity in vivo. These constructs differ by the number of Stat92E binding sites
      and the stability of GFP. The 2XSTAT92E-GFP and 10XSTAT92E-GFP constructs contain
      2 and 10 Stat92E binding sites, respectively, driving expression of enhanced GFP,
      while 10XSTAT92E-DGFP drives expression of destabilized GFP. We show that these
      reporters are expressed in the embryo in an overlapping pattern with Stat92E
      protein and in tissues where JAK/STAT signaling is required. In addition, these
      reporters accurately reflect JAK/STAT pathway activity at larval stages, as their
      expression pattern overlaps that of the activating ligand unpaired in imaginal
      discs. Moreover, the STAT92E-GFP reporters are activated by ectopic JAK/STAT
      signaling. STAT92E-GFP fluorescence is increased in response to ectopic upd in
      the larval eye disc and mis-expression of the JAK kinase hopscotch in the adult
      fat body. Lastly, these reporters are specifically activated by Stat92E, as
      STAT92E-GFP reporter expression is lost cell-autonomously in stat92E homozygous
      mutant tissue. In sum, we have generated in vivo GFP reporters that accurately
      reflect JAK/STAT pathway activation in a variety of tissues. These reporters are
      valuable tools to further investigate and understand the role of JAK/STAT
      signaling in Drosophila.

PMID- 17008135
TI  - Shape patterns of genital papillae in pinworms (Enterobiinae, Oxyurida, Nematoda)
      parasite of primates: a landmark analysis.
AB  - The Enterobiinae includes 47 species of pinworms parasite of primates. A previous
      cladistic analysis of this subfamily supported its monophyly and its subdivision
      into three genera. Based on morphological characters, this cladistic analysis
      excluded characters describing the shape of the genital papillae of male
      pinworms, because the corresponding patterns could not be described using
      discrete characters. In this study, the shape of the genital papillae of the
      males of 35 within the 47 species is analyzed using geometric morphometric
      approaches. The aims of this study are to investigate: (i) the relationships
      between the phylogeny and the shape patterns of the caudal bursa, (ii) the shape
      differences between and within monophyletic groups, and (iii) the functional
      implications of the shape patterns observed within the subfamily. Results
      demonstrate that different patterns of evolution of the caudal bursa, each one
      characterized by a particular spatial distribution of the phasmids and genital
      papillae may be recognized, which are consistent with the classification of the
      Enterobiinae into three groups. On the whole, these patterns may be related to
      particular mating behavior of the pinworms. When incongruence is observed between
      shape patterns distribution and species distribution into monophyletic groups,
      they are found to correspond to homoplasic events. This suggests that convergent
      selective pressures are involved in the evolution of the shape of the genital
      papillae. This analysis also confirms that morphometric shape patterns cannot be
      interpreted unequivocally without the support of a pre-existing phylogenetic
      framework.

PMID- 17008136
TI  - Quantitative profiling of the pathological prion protein allotypes in bank voles
      by liquid chromatography-mass spectrometry.
AB  - The conversion of the cellular prion protein (PrP(C)) into a misfolded isoform
      (PrP(TSE)) that accumulates in the brain of affected individuals is the key
      feature of transmissible spongiform encephalopaties (TSEs). Susceptibility to
      TSEs is influenced by polymorphisms of the prion gene suggesting that the
      presence of certain amino acid residues may facilitate the pathological
      conversion. In this work, we describe a quantitative, fast and reliable HPLC-MS
      method that allowed to demonstrate that in the brain of 109(Met/Ile) heterozygous
      bank voles infected with the mouse adapted scrapie strain 139A, there are
      comparable amounts of PrP(TSE) with methionine or isoleucine in position 109,
      suggesting that in this TSE model the two allotypes have similar rates of
      accumulation. This method can be easily adapted for the quantitative
      determination of PrP allotypes in the brain of other natural or experimental TSE
      models.

PMID- 17008137
TI  - Fast differentiation of meats from fifteen animal species by liquid
      chromatography with electrochemical detection using copper nanoparticle plated
      electrodes.
AB  - A simple, rapid and reliable method based on high-performance liquid
      chromatography with electrochemical detection was developed to routinely
      differentiate among meat products from fifteen food animal species. Samples from
      cattle, pigs, goats, deer, horses, chickens, ducks, ostriches, salmon, cod,
      shrimp, crabs, scallops, bullfrogs and alligators each exhibited unique
      electrochemical profiles. Species-specific markers exhibited reproducible peak
      retention times with coefficients of variation less then 6% across different
      runs, body regions and subjects. The method requires no derivatization or
      extraction steps and may be applicable to fresh or cooked meats. Incubation of
      fresh beef, pork or chicken at room temperature for 24h or repeated freezing and
      thawing changed the intensity but not the pattern of species-specific peaks. In
      conclusion, this method appears suitable for rapid differentiation of meats from
      various food animal species and demonstrates the utility of electrochemical
      detection to supplement existing immunochemical and molecular biological methods.
      The possibility of using this method to detect adulteration and degradative
      changes of meat proteins is discussed.

PMID- 17008138
TI  - Picosecond dynamics of T and R forms of aspartate transcarbamylase: a neutron
      scattering study.
AB  - E. coli aspartate transcarbamylase (ATCase) is a 310 kDa allosteric enzyme which
      catalyses the first committed step in pyrimidine biosynthesis. The binding of its
      substrates, carbamylphosphate and aspartate, induces significant conformational
      changes. This enzyme shows homotropic cooperative interactions between the
      catalytic sites for the binding of aspartate. This property is explained by a
      quaternary structure transition from T state (aspartate low affinity) to R state
      (aspartate high affinity) accompanied by a 5% increase of radius of gyration of
      ATCase. The same quaternary structure change is observed upon binding of the
      bisubstrate analogue PALA (N-(phosphonacetyl)-L-aspartate. Owing to the large
      incoherent neutron scattering cross-section of the hydrogen atom and the
      abundance of this element in proteins, inelastic neutron scattering gives a
      global view of protein dynamics as sensed via the individual motions of its
      hydrogen atoms. We present neutron scattering results of the local dynamics (few
      angstroms), at short time (few tens of picoseconds), of ATCase in T and R forms.
      Compared to the T form, we observe an increased mobility of the protein in the R
      form that we associate to an increase of accessible surface area to the solvent.
      Beyond this specific result, this highlights the key role of the accessible
      surface area (ASA) in dynamic contribution to inelastic neutron data in the
      picosecond time scale. In particular, we want to stress out (i) that a difference
      at the picosecond time scale does not allow to conclude to a difference in the
      dynamics at a longer time scale and to address whether the T state is looser than
      the R state (ii) how challenging is, any comparison in terms of general dynamics
      (tense or relaxed) between dynamic values deduced from experimental neutron data
      on proteins with different sequences and therefore ASA. This caveat holds
      particularly when comparing dynamics of a mesophile with the corresponding
      extremophile.

PMID- 17008139
TI  - A case of long latency amoebic liver abscess in a nonendemic country: the clue
      diagnostic value of subtle colonoscopic changes.

PMID- 17008141
TI  - Special issue on proton transfer in biological systems.

PMID- 17008142
TI  - Stress and its consequences: an evolving story.

PMID- 17008144
TI  - Longitudinal assessment of cognitive performance in Holocaust survivors with and
      without PTSD.
AB  - BACKGROUND: There are currently no longitudinal studies of cognitive performance
      in older patients with Posttraumatic Stress Disorder (PTSD). It is therefore
      unclear whether relationships between memory and symptoms differ over time among
      older persons with and without PTSD. METHODS: Twenty-eight Holocaust survivors
      and nineteen comparison subjects were evaluated 5 years after they had received a
      memory assessment including paired-associates learning and the California Verbal
      Learning Test (CVLT). RESULTS: While Holocaust survivors with PTSD showed a
      diminution in symptom severity (t = 2.99, df = 12, p = .011), they still
      manifested a decline in paired associates learning, suggesting an acceleration in
      age-related memory impairment (related word pairs: t = 2.87, df = 13, p = .013;
      unrelated word pairs: t = 2.06, df = 13, p = .060). The survivors with PTSD
      showed improvements on several CVLT measures over time. These improvements
      correlated with symptom improvements, such that group differences at the follow
      up were no longer detected. CONCLUSIONS: The discrepancy in the pattern of
      performance on these two tests of memory following symptom improvement suggests
      possible differentiation between of aspects of memory functions associated with
      aging and trauma exposure and those associated with the severity of PTSD
      symptoms. Performance on the CVLT appeared related to clinical symptom severity
      while paired associate learning worsened over time in Holocaust survivors with
      PTSD, consistent with earlier cross-sectional findings.

PMID- 17008143
TI  - Childhood maltreatment, subsequent antisocial behavior, and the role of monoamine
      oxidase A genotype.
AB  - BACKGROUND: A functional promoter polymorphism in monoamine oxidase A (MAOA) has
      been implicated as a moderating factor in the relationship between childhood
      maltreatment and later adolescent and adult antisocial behavior. Despite wide
      interest in this hypothesis, results remain mixed from the few attempts at
      replication. METHODS: Regression-based analyses were conducted to test for a
      genotype-environment interaction using self-reported physical abuse and MAOA
      genotype to predict later antisocial behavior and arrests for violence by
      participants in the National Youth Survey Family Study. We also examined the
      interaction using a measure of violent victimization. The analysis sample
      included 277 Caucasian male respondents, aged 11-15 in 1976, who provided buccal
      swab DNA samples and who were successfully genotyped for the variable number
      tandem repeat (VNTR) in the MAOA promoter using polymerase chain reaction.
      RESULTS: Maltreatment by a parent during adolescence was a risk factor for
      adolescent and adult antisocial and violence related behavioral problems. Tests
      for the main effect of MAOA and a MAOA-maltreatment interaction were
      nonsignificant. Similar results were obtained using the measure of adolescent
      violent victimization. CONCLUSIONS: Findings from this general population sample
      could not confirm the hypothesis that MAOA moderates the relationship between
      adolescent maltreatment and adolescent or adult antisocial behavior.

PMID- 17008145
TI  - Psychobiological characteristics of dissociative identity disorder: a symptom
      provocation study.
AB  - BACKGROUND: Dissociative identity disorder (DID) patients function as two or more
      identities or dissociative identity states (DIS), categorized as 'neutral
      identity states' (NIS) and 'traumatic identity states' (TIS). NIS inhibit access
      to traumatic memories thereby enabling daily life functioning. TIS have access
      and responses to these memories. We tested whether these DIS show different
      psychobiological reactions to trauma-related memory. METHODS: A symptom
      provocation paradigm with 11 DID patients was used in a two-by-two factorial
      design setting. Both NIS and TIS were exposed to a neutral and a trauma-related
      memory script. Three psychobiological parameters were tested: subjective ratings
      (emotional and sensori-motor), cardiovascular responses (heart rate, blood
      pressure, heart rate variability) and regional cerebral blood flow as determined
      with H(2)(15)O positron emission tomography. RESULTS: Psychobiological
      differences were found for the different DIS. Subjective and cardiovascular
      reactions revealed significant main and interactions effects. Regional cerebral
      blood flow data revealed different neural networks to be associated with
      different processing of the neutral and trauma-related memory script by NIS and
      TIS. CONCLUSIONS: Patients with DID encompass at least two different DIS. These
      identities involve different subjective reactions, cardiovascular responses and
      cerebral activation patterns to a trauma-related memory script.

PMID- 17008146
TI  - Naltrexone and disulfiram in patients with alcohol dependence and comorbid post
      traumatic stress disorder.
AB  - BACKGROUND: Although disulfiram and naltrexone have been approved by the Food and
      Drug Administration for the treatment of alcoholism, the effect of these
      medications on alcohol use outcomes and on psychiatric symptoms is still unknown
      in patients with co-occurring disorders post-traumatic stress disorder (PTSD).
      METHODS: Patients (n = 254) with a major Axis I psychiatric disorder and comorbid
      alcohol dependence were treated for 12 weeks in a medication study at three
      Veterans Administration outpatient clinics. Randomization included (1) open
      randomization to disulfiram or no disulfiram; and (2) double-blind randomization
      to naltrexone or placebo. This resulted in four groups: (1) naltrexone alone; (2)
      placebo alone; (3) disulfiram and naltrexone; or (4) disulfiram and placebo.
      Outcomes were measures of alcohol use, PTSD symptoms, alcohol craving, GGT levels
      and adverse events. RESULTS: 93 individuals (36.6%) met DSM-IV criteria for PTSD.
      Subjects with PTSD had better alcohol outcomes with active medication
      (naltrexone, disulfiram or the combination) than they did on placebo; overall
      psychiatric symptoms of PTSD improved. Individuals with PTSD were more likely to
      report some side effects when treated with the combination. CONCLUSIONS: The
      results of this study suggest that disulfiram and naltrexone are effective and
      safe for individuals with PTSD and comorbid alcohol dependence.

PMID- 17008147
TI  - Oocyte cryopreservation.
AB  - OBJECTIVE: To review historical and contemporary advances in oocyte
      cryopreservation techniques and outcomes. DESIGN: Publications related to oocyte
      cryopreservation were identified through MEDLINE and other bibliographic
      databases. CONCLUSION(S): Oocyte cryopreservation can be used as an adjunct to
      conventional IVF and as an option for fertile women to electively cryopreserve
      their gametes. Recent reports indicate pregnancy rates comparable to those for
      cryopreserved embryos by either slow-freeze or vitrification methods. Larger
      prospective trials are needed to determine the true efficacy and safety of oocyte
      cryopreservation. Until a sufficient number of births is reached and adequate
      outcome data are collected, oocyte cryopreservation should continue to be
      considered experimental and to be performed under the oversight of an
      institutional review board.

PMID- 17008148
TI  - Effect of oxidized regenerated cellulose (Interceed) on the expression of tissue
      plasminogen activator and plasminogen activator inhibitor-1 in human peritoneal
      fibroblasts and mesothelial cells.
AB  - OBJECTIVE: To characterize the molecular changes that occur in normal
      fibroblasts, adhesion fibroblasts, and mesothelial cells as a result of exposure
      to oxidized regenerated cellulose (Interceed; Johnson & Johnson Medical, Inc.,
      New Brunswick, NJ). DESIGN: Control and Interceed-treated normal peritoneal
      fibroblasts, adhesion fibroblasts, and mesothelial cells in culture were assessed
      for messenger RNA levels of molecules known to be associated with adhesion
      development, using multiplex reverse transcriptase polymerase chain reaction (n =
      4). SETTING: University research laboratory. PATIENT(S): Normal and adhesion
      fibroblasts and mesothelial cells. INTERVENTION(S): Exposure of cells, normal
      fibroblasts, adhesion fibroblasts, and mesothelial cells to oxidized regenerated
      cellulose. MAIN OUTCOME MEASURE(S): Real-time reverse transcriptase polymerase
      chain reaction expression of messenger RNA tissue plasminogen activator (tPA),
      plasminogen activator inhibitor-1 (PAI-1), and tPA-PAI-1 ratio, an indicator of
      overall fibrinolytic activity. RESULT(S): Interceed treatment of normal
      peritoneal fibroblasts, adhesion fibroblasts, and mesothelial cells results in an
      increased expression of tPA in mesothelial cells and an increase in the tPA-PAI-1
      ratio, signifying an overall increase in fibrinolytic activity. CONCLUSION(S):
      Interceed, which has been shown in multiple human in vivo studies to decrease
      postoperative adhesion development, increases the expression of tPA and the tPA
      PAI-1 ratio (an indicator of overall fibrinolytic activity), thereby promoting
      dissolution of fibrin and healing without adhesion development. Thus, the ability
      of Interceed to reduce postoperative adhesion development may be derived from
      both a barrier and biologic effect.

PMID- 17008149
TI  - Effects of oxygen tension on gene expression in preimplantation mouse embryos.
AB  - OBJECTIVE: To compare the effects of atmospheric and physiologic oxygen
      concentrations on the global patterns of gene expression during mouse
      preimplantation development. DESIGN: Comparative analysis of in vivo-produced and
      in vitro-produced embryos. SETTING: Research laboratory. PATIENT(S): None.
      INTERVENTION(S): Control embryos at the blastocyst stage that developed in vivo
      were collected from uteri. Experimental embryos were obtained at the zygote stage
      and cultured to the blastocyst stage in Whitten's medium or KSOM medium with
      amino acids under 20% oxygen (atmospheric) or 5% oxygen (physiologic). MAIN
      OUTCOME MEASURE(S): Embryo development, cell number, and gene expression assayed
      by microarray technology. RESULT(S): Low (physiologic) oxygen concentration is
      associated with faster embryo development and increased cell number. In addition,
      there are marked perturbations in the global pattern of gene expression, as
      assessed by oligonucleotide microarray, after culture in 20% oxygen as compared
      with 5% oxygen. CONCLUSION(S): Culture in low oxygen is associated with fewer
      perturbations in the global pattern of gene expression and more closely resembles
      that of the in vivo control embryos. These findings provide rationale for
      culturing human embryos in the presence of 5%, rather than 20%, oxygen.

PMID- 17008150
TI  - Innovative barriers for peritoneal adhesion prevention: liquid or solid? A rat
      uterine horn model.
AB  - OBJECTIVE: To compare the effects of solid barriers (PDLA membrane and foil,
      Interceed), innovative barrier solutions (Adept and Hyalobarrier Gel,
      phospholipid emulsion), and Ringer's lactate solution in preventing postsurgical
      peritoneal adhesions in the rat. DESIGN: Prospective, randomized experimental
      study. SETTING: Rat model in an academic research environment. ANIMAL(S): Female,
      nonpregnant Wistar rats. INTERVENTION(S): Standardized surgical injuries were
      applied to the parietal and visceral peritoneum and the uterine horns. The
      barrier agents were applied and the wound was closed. A second-look laparoscopy
      was performed 31 days after surgery to assess adhesion formation. MAIN OUTCOME
      MEASURE(S): Severity and extent of adhesion formation assessed using a
      multidimensional adhesion scoring system. RESULT(S): Significantly fewer
      postsurgical adhesions were seen after treatment with Adept, Hyalobarrier Gel,
      Interceed, PDLA membrane, and phospholipid emulsion than after Ringer's lactate
      solution. Severe, clinically relevant adhesions were not observed after
      Hyalobarrier Gel and in only one animal after Adept. CONCLUSION(S): Both solid
      and liquid barriers can prevent adhesions. Hydroflotation formulas, such as Adept
      and Hyalobarrier Gel, avoid suture-induced adhesions, are easy to use, and their
      protective effects are evenly distributed. They are suitable for adhesion
      prevention after multifocal trauma in rats, and require further testing in the
      everyday clinical situation.

PMID- 17008151
TI  - The new marine green? Sustainability and health challenges for coastal
      communities.

PMID- 17008153
TI  - Chemistry of gluten proteins.
AB  - Gluten proteins play a key role in determining the unique baking quality of wheat
      by conferring water absorption capacity, cohesivity, viscosity and elasticity on
      dough. Gluten proteins can be divided into two main fractions according to their
      solubility in aqueous alcohols: the soluble gliadins and the insoluble glutenins.
      Both fractions consist of numerous, partially closely related protein components
      characterized by high glutamine and proline contents. Gliadins are mainly
      monomeric proteins with molecular weights (MWs) around 28,000-55,000 and can be
      classified according to their different primary structures into the alpha/beta-,
      gamma- and omega-type. Disulphide bonds are either absent or present as
      intrachain crosslinks. The glutenin fraction comprises aggregated proteins linked
      by interchain disulphide bonds; they have a varying size ranging from about
      500,000 to more than 10 million. After reduction of disulphide bonds, the
      resulting glutenin subunits show a solubility in aqueous alcohols similar to
      gliadins. Based on primary structure, glutenin subunits have been divided into
      the high-molecular-weight (HMW) subunits (MW=67,000-88,000) and low-molecular
      weight (LMW) subunits (MW=32,000-35,000). Each gluten protein type consists or
      two or three different structural domains; one of them contains unique repetitive
      sequences rich in glutamine and proline. Native glutenins are composed of a
      backbone formed by HMW subunit polymers and of LMW subunit polymers branched off
      from HMW subunits. Non-covalent bonds such as hydrogen bonds, ionic bonds and
      hydrophobic bonds are important for the aggregation of gliadins and glutenins and
      implicate structure and physical properties of dough.

PMID- 17008154
TI  - Biodiversity and identification of sourdough lactic acid bacteria.
AB  - This review deals with recent developments on the biodiversity of sourdough
      lactic acid bacteria (LAB) and the recent description of new sourdough LAB
      species. One of the outcomes of biodiversity studies of particular sourdough
      ecosystems throughout Europe is the description of new taxa of LAB. During the
      last 3 years, several new LAB species have been isolated from traditional
      sourdoughs: Lactobacillus mindensis, Lactobacillus spicheri, Lactobacillus
      rossiae, Lactobacillus zymae, Lactobacillus acidifarinae, Lactobacillus hammesii,
      and Lactobacillus nantensis. Some of these species have been described on one
      single isolate only. Isolation of novel taxa mainly depends on the cultivation
      approach used, i.e. (selective) incubation media and conditions. The distribution
      of the taxa of LAB is highly variable from one sourdough ecosystem to another.
      Therefore, it is difficult to define correlations between population composition
      and both the type of sourdough or the geographic location. Identification of
      isolated strains needs a polyphasic approach, including a combination of
      phenotypic and genotypic methods, the latter often based on the polymerase chain
      reaction (PCR) and encompassing 16S rRNA sequencing and DNA-DNA hybridizations. A
      main obstacle in current identification approaches of LAB strains is the lack of
      a robust and exchangeable identification system for all LAB species. Recent
      studies based on complete genomes have provided the basis for establishing sets
      of genes useful for multi-locus sequence analysis (MLSA). Monitoring the
      population dynamics of sourdough ecosystems can be performed by both culture
      dependent (plating and incubation) and culture-independent (e.g. PCR-Denaturing
      Gradient Gel Electrophoresis) methods. Although highly valuable for community
      fingerprinting, culture-independent methods do not always yield precise
      quantitative information.

PMID- 17008155
TI  - Carbohydrate, peptide and lipid metabolism of lactic acid bacteria in sourdough.
AB  - The metabolic pathways of lactic acid bacteria that influence bread quality are
      coupled to the central carbon flux by the availability of cofactors influencing
      the cellular and environmental redox potential. Homo- and heterofermentative
      metabolism differ fundamentally with respect to the requirement for regeneration
      of reduced cofactors, NADH or NADPH. The utilization of co-substrates such as
      oxygen or fructose as electron acceptors by obligate heterofermentative
      lactobacilli is coupled to an increased production of acetate in dough. Recently,
      several oxidoreductases involved in cofactor regeneration were characterized and
      glutathione and short-chain aldehydes derived from lipid oxidation were
      identified as substrates for cofactor regeneration by Lactobacillus
      sanfranciscensis. Based on the different metabolic requirements for cofactor
      regeneration, homo- and heterofermentative lactobacilli exert divergent effects
      on redox-reactions in sourdough that influence bread quality beyond the formation
      of acetate. Proteolysis, followed by peptide or amino acid metabolism by LAB is
      one of the key routes of flavour formation in bread flavour, and enables the
      strain-specific formation of antifungal metabolites. Peptide metabolism as well
      as the metabolism of cysteine, arginine, and phenylalanine in Lactobacillus
      plantarum, L. sanfranciscensis, and Lactobacillus pontis is increasingly
      understood and these insights provide new opportunities for the directed
      application of sourdough LAB for improved bread quality.

PMID- 17008156
TI  - Generation of aroma compounds in sourdough: effects of stress exposure and
      lactobacilli-yeasts interactions.
AB  - The effects of the interaction between Saccharomyces cerevisiae LBS and
      Lactobacillus sanfranciscensis LSCE1 and of their responses to acid, oxidative or
      osmotic stress on alcohol and aroma production were assessed. The exposure of S.
      cerevisiae LBS and L. sanfranciscensis LSCE1 cells to oxidative, acid or osmotic
      sub-lethal stress gave rise to a common or specific responses. Gamma-decalactone,
      2(5H)-furanones and aldehydes were overproduced by LAB following oxidative
      stress. The acid stress induced both in yeasts and LAB, as well as in their co
      cultures, a relevant accumulation of isovaleric and acetic acids and higher
      alcohols. A cross-exposure of yeasts and LAB to their preconditioned media,
      generated in S. cerevisiae a release of esters including esters of long-chain
      unsaturated fatty acids coming from membrane phospholipids. These esters were
      excreted also by yeasts following a pressure stress.

PMID- 17008158
TI  - Liquid sourdough fermentation: industrial application perspectives.
AB  - Sourdough fermentation is considered to play a key role to get improved flavour,
      texture, nutritional and shelf-life properties of bakery products. Since few
      years Barilla R&D has been focusing on liquid sourdough fermentation which may
      deserve several advantages with respect to traditional processes. The results
      showed that the micro-biota of sourdough markedly influences flavour and texture
      of bakery products. Particular attention has been paid to lactic acid bacteria
      and yeasts. Selected lactic acid bacteria and yeasts were tested in sourdough
      liquid fermentation as single strain or in association. The parameters of
      fermentations were optimized and standardized to set up a laboratory plant liquid
      fermentation. Only a few strains of lactic acid bacteria were found to be
      suitable for liquid fermentation alone or in association with yeasts.
      Fermentations were carried out at pilot plant and an industrial technology was
      developed. This work describes the results found for the organoleptic profile of
      an industrial bread started with liquid sourdough with respect to bakers' yeast
      bread without sourdough addition.

PMID- 17008159
TI  - Emerging fermentation technologies: development of novel sourdoughs.
AB  - The increasing knowledge of sourdough fermentation generates new opportunities
      for its use in the bakery field. New fermentation technologies emerged through in
      depth sourdough research. Dextrans are extracellular bacterial polysaccharides
      produced mainly by lactic acid bacteria (LAB). These bacteria convert sucrose
      thanks to an inducible enzyme called dextransucrase into dextran and fructose.
      The structure of dextran depends on the producing micro-organism and on culture
      conditions. Depending on its structure, dextran has specific properties which
      lead to several industrial applications in different domains. The use of dextran
      is not widely spread in the bakery field even if its impact on bread volume and
      texture was shown. A new process has been developed to obtain a sourdough rich in
      dextran using a specific LAB strain able to produce a sufficient amount of HMW
      dextran assuring a significant impact on bread volume. The sourdough obtained
      permits to improve freshness, crumb structure, mouthfeel and softness of all
      kinds of baked good from wheat rich dough products to rye sourdough breads. From
      fundamental research on dextran technology, a new fermentation process has been
      developed to produce an innovative functional ingredient for bakery industry.

PMID- 17008160
TI  - Sourdough products for convenient use in baking.
AB  - Sourdough fermentations require a specific knowledge on the effects of process
      parameters, raw materials and micro-organisms in order to obtain a specific,
      reproducible sourdough and bread quality. This knowledge is not necessarily
      available in bakeries. Sourdough starter cultures, either active sourdoughs
      (Reinzuchtsauerteig) or freeze-dried micro-organisms are used to start sourdough
      fermentation with the required micro-flora. As sourdough fermentation is a labour
      intensive and a time-consuming process, a growing demand for convenient products
      arised early. First organic acids (lactic acid, acetic acid, citric acid) and
      mixtures thereof came in use. These agents were used directly without or in
      combination with a sourdough; however, flavour and taste of the resulting breads
      were unsatisfactory. Based on modified and optimized traditional sourdough
      processes, dried, pasty and liquid sourdoughs were developed. Companies which
      produce such ready-to-use products, claim for a convenient, direct production of
      baked goods in constant quality, in combination with all advantages of a
      biological sourdough fermentation, e.g. flavour and taste, fresh keeping and
      prolonged microbial shelf-life. Currently, a broad variety of sourdough products
      with different fermented cereals is available on the market. In order to obtain a
      stable product, it is a necessity to inactivate the sourdough micro-biota by e.g.
      pasteurization, drying or autosterilization.

PMID- 17008161
TI  - Impact of sourdough on the texture of bread.
AB  - Sourdough has been used since ancient times and its ability to improve the
      quality and increase the shelf-life of bread has been widely described. During
      sourdough fermentation, lactic acid bacteria (LAB) produce a number of
      metabolites which have been shown to have a positive effect on the texture and
      staling of bread, e.g. organic acids, exopolysaccharides (EPS) and/or enzymes.
      EPS produced by LAB have the potential to replace more expensive hydrocolloids
      used as bread improvers. Organic acids affect the protein and starch fractions of
      flour. Additionally, the drop in pH associated with acid production causes an
      increase in the proteases and amylases activity of the flour, thus leading to a
      reduction in staling. While improving the textural qualities of bread, sourdough
      fermentation also results in increased mineral bioavailability and reduced
      phytate content. In this review we will be discussing the effect of sourdough on
      wheat and rye bread as well as the potential of sourdough to improve the quality
      of gluten-free bread.

PMID- 17008162
TI  - Bran fermentation as a means to enhance technological properties and bioactivity
      of rye.
AB  - Response surface methodology was applied to study the effects of fermentation on
      the levels of phytochemicals (folates, phenolic compounds, alkylresorcinols) and
      on the solubilization of pentosans in rye bran from native and peeled grains.
      Furthermore, the microbial composition of the brans before and after fermentation
      was studied. Peeling reduced the microbial load and lower microbial counts were
      detected in the fermentation experiments carried out with the bran from peeled
      grains. High temperature and long fermentation time favoured the growth of
      indigenous lactic acid bacteria (LAB), and a diverse microbial community was
      detected. The brans contained low levels of aerobic spore-forming bacteria, but
      their number was not increased during the fermentations. Fermentation of both
      brans increased the levels of folates, easily extractable total phenolics and
      free ferulic acid. During fermentation of bran from native grains, the levels of
      alkylresorcinols slightly increased but during fermentation of bran from peeled
      grains they decreased. Significant increase in soluble pentosans was established
      in both types of rye bran fermentations. Enhanced bioactivity and solubilization
      of pentosans with limited microbial growth were obtained after 12-14 h
      fermentation at 25 degrees C. The results suggest that fermentation is a
      potential bioprocessing technology for improved technological properties and
      bioactivity of rye bran.

PMID- 17008163
TI  - Sourdough lactobacilli and celiac disease.
AB  - Celiac disease (CD) is one of the most common food intolerance. The only
      effective treatment for CD is a strict adherence to a gluten-free diet throughout
      the patient's lifetime. Gluten-free products are not widely available and are
      usually more expensive than their gluten-containing counterparts. There is,
      therefore, an urgent need to develop safe and effective therapeutic alternatives,
      to develop high-quality gluten-free products and to investigate the potential of
      the bread making biotechnology following ancient protocols which include long
      time fermentation by selected sourdough lactic acid bacteria. This review
      describes the most relevant results related to biotechnologies that use selected
      sourdough lactic acid bacteria and probiotics as starters for sourdough
      fermentation to investigate their potential to decrease the risk of gluten
      contamination in gluten-free products. As shown by studies in vitro on celiac
      intestinal tissue and in vivo on CD patients, the bacterial proteolytic activity
      is rather promising not only as currently demonstrated for eliminating traces of
      contaminant gluten but probably also in perspective for the manufacture of
      tolerated baked goods.

PMID- 17008164
TI  - Testing for heparin-induced thrombocytopenia antibodies.
AB  - Heparin-induced thrombocytopenia (HIT) has a distinct clinical profile and unique
      pathogenesis. It is caused by platelet-activating IgG antibodies that recognize
      multimolecular complexes of platelet factor 4 (PF4) bound to heparin or certain
      other polyanions. Although an immune response to PF4/heparin associated with
      heparin treatment is very common, clinical HIT occurs only among the minority of
      patients whose antibodies are capable of strongly activating platelets. This
      explains why certain platelet activation assays and anti-PF4/polyanion
      immunoassays have high sensitivity for HIT and why diagnostic specificity is
      highest for those assays that preferentially detect pathogenic antibodies, such
      as the washed platelet activation assays or immunoassays that detect only IgG
      antibodies. Negative results obtained in a solid-phase PF4/polyanion immunoassay
      generally exclude HIT (high negative predictive value), especially in a setting
      of a low pretest probability. In addition, because the magnitude of a positive
      test result correlates with greater likelihood of HIT, a Bayesian diagnostic
      approach that combines pretest probability and the magnitude of a positive test
      result is recommended. Recent studies suggest that presence of anti-PF4/polyanion
      antibodies in certain clinical settings confers an adverse prognosis, even
      without clinically evident HIT. Whether such antibodies impart "forme fruste" HIT
      or are simply a surrogate marker for a non-HIT adverse risk factor such as
      inflammation is unresolved.

PMID- 17008165
TI  - Serious hazards of transfusion: a decade of hemovigilance in the UK.
AB  - The Serious Hazards of Transfusion (SHOT) scheme is a UK-wide, independent,
      professionally led hemovigilance system focused on learning from adverse events.
      SHOT was established in 1996 as a confidential reporting system for significant
      transfusion-related events, building an evidence base to support blood safety
      policy decisions, clinical guidelines, clinician education, and improvements in
      transfusion practice. Recommendations are formulated by an independent steering
      group drawn from medical royal colleges and professional bodies. Ten years after
      its inception, SHOT has analyzed 2630 transfusion safety events, published 8
      annual reports with recommendations, and presented data nationally and
      internationally. These recommendations have underpinned key initiatives, in
      particular the UK Department of Health "Better Blood Transfusion" strategy. SHOT
      has encouraged open reporting of adverse events and "near-misses" in a
      supportive, learning culture, vigilance in hospital transfusion practice, and
      evaluation of information technology to support this process. The importance of
      education and training has been emphasized. Detailed analysis of events has
      identified weaknesses in the transfusion chain. A collaborative initiative
      between SHOT, the Chief Medical Officer for England's National Blood Transfusion
      Committee, and the National Patient Safety Agency aims to reduce ABO-incompatible
      transfusions by improving bedside practice. Cumulative SHOT data have documented
      the decline in transfusion-related graft vs host disease after implementation of
      leucodepletion and have highlighted transfusion-related acute lung injury and
      bacterial contamination of platelets as important causes of death and morbidity.
      The UK blood services have developed strategies to reduce these risks. Future
      SHOT data will evaluate the success of these and other blood safety improvements.

PMID- 17008166
TI  - Clinical approaches involving thrombopoietin to shorten the period of
      thrombocytopenia after high-dose chemotherapy.
AB  - High-dose chemotherapy followed by a peripheral blood stem cell transplant is
      successfully used for a wide variety of malignancies. A major drawback, however,
      is the delay in platelet recovery. Several clinical strategies using
      thrombopoietin (Tpo) have been developed in an attempt to speed up platelet
      repopulation. In contrast to its success in immune thrombocytopenia and in low
      dose toxic chemotherapeutic regimens, Tpo appears less effective in the case of
      high-dose chemotherapy and peripheral blood stem cell transplant. To develop a
      successful therapeutic approach, more knowledge is needed on several aspects of
      megakaryocyte (progenitor) biology, such as homing to the bone marrow,
      endomitosis, and platelet formation. Interactions of the megakaryocytes with the
      marrow vasculature and the microvascular microenvironment are other key factors
      for optimal thrombocytopoiesis. The present report reviews the background of the
      inefficiency of Tpo after intensive chemotherapy and describes possible
      strategies that might lead to successful therapies to treat chemotherapy-induced
      thrombocytopenia.

PMID- 17008168
TI  - Watching the world wash its hands of sanitation.

PMID- 17008167
TI  - Platelet immunopathology and therapy: a Canadian Blood Services Research and
      Development Symposium.

PMID- 17008169
TI  - No evidence for capsule replacement following mass immunisation with
      meningococcal serogroup C conjugate vaccines in England and Wales.

PMID- 17008171
TI  - What's brewing?

PMID- 17008172
TI  - The worldwide emergence of plasmid-mediated quinolone resistance.
AB  - Fluoroquinolone resistance is emerging in gram-negative pathogens worldwide. The
      traditional understanding that quinolone resistance is acquired only through
      mutation and transmitted only vertically does not entirely account for the
      relative ease with which resistance develops in exquisitely susceptible
      organisms, or for the very strong association between resistance to quinolones
      and to other agents. The recent discovery of plasmid-mediated horizontally
      transferable genes encoding quinolone resistance might shed light on these
      phenomena. The Qnr proteins, capable of protecting DNA gyrase from quinolones,
      have homologues in water-dwelling bacteria, and seem to have been in circulation
      for some time, having achieved global distribution in a variety of plasmid
      environments and bacterial genera. AAC(6')-Ib-cr, a variant aminoglycoside
      acetyltransferase capable of modifying ciprofloxacin and reducing its activity,
      seems to have emerged more recently, but might be even more prevalent than the
      Qnr proteins. Both mechanisms provide low-level quinolone resistance that
      facilitates the emergence of higher-level resistance in the presence of
      quinolones at therapeutic levels. Much remains to be understood about these
      genes, but their insidious promotion of substantial resistance, their horizontal
      spread, and their co-selection with other resistance elements indicate that a
      more cautious approach to quinolone use and a reconsideration of clinical
      breakpoints are needed.

PMID- 17008173
TI  - Evidence-based model for hand transmission during patient care and the role of
      improved practices.
AB  - Hand cleansing is the primary action to reduce health-care-associated infection
      and cross-transmission of antimicrobial-resistant pathogens. Patient-to-patient
      transmission of pathogens via health-care workers' hands requires five sequential
      steps: (1) organisms are present on the patient's skin or have been shed onto
      fomites in the patient's immediate environment; (2) organisms must be transferred
      to health-care workers' hands; (3) organisms must be capable of surviving on
      health-care workers' hands for at least several minutes; (4) handwashing or hand
      antisepsis by the health-care worker must be inadequate or omitted entirely, or
      the agent used for hand hygiene inappropriate; and (5) the caregiver's
      contaminated hand(s) must come into direct contact with another patient or with a
      fomite in direct contact with the patient. We review the evidence supporting each
      of these steps and propose a dynamic model for hand hygiene research and
      education strategies, together with corresponding indications for hand hygiene
      during patient care.

PMID- 17008175
TI  - Sputum processing methods to improve the sensitivity of smear microscopy for
      tuberculosis: a systematic review.
AB  - In low-income and middle-income countries, direct (unconcentrated) sputum smear
      microscopy is the primary method for diagnosing pulmonary tuberculosis. The
      method is fast, inexpensive, and specific for Mycobacterium tuberculosis in high
      incidence areas. The main limitations of direct microscopy are its relatively low
      sensitivity, especially in individuals co-infected with HIV, and variable quality
      of the test in programme conditions. Thus, there is a need to identify methods to
      improve the sensitivity of microscopy. Physical and chemical sputum processing
      methods, including centrifugation, sedimentation, and bleach, have been studied
      and found to show promise. We did a systematic review to assess the ability of
      different processing methods to improve the sensitivity of microscopy. By
      searching many sources, we identified 83 studies. Overall, by comparison with
      direct smears, the results suggested that centrifugation with any of several
      chemical methods (including bleach) is more sensitive, that overnight
      sedimentation preceded by chemical processing is more sensitive, and that
      specificity is similar. There were insufficient data to determine the value of
      sputum processing methods in patients with HIV infection. Operational studies are
      needed to determine whether the increased sensitivity provided by processing
      methods is sufficient to offset their increased cost, complexity, and potential
      biohazards, and to examine their feasibility.

PMID- 17008176
TI  - The polio eradication effort has been a great success--let's finish it and
      replace it with something even better.
AB  - The polio eradication campaign has greatly reduced the effects of this disease,
      but many new challenges have emerged. These challenges include the occurrence of
      polio outbreaks caused by wild-type polioviruses or circulating vaccine-derived
      polioviruses (cVDPVs) in areas where vaccination coverage is low, the existence
      of people who excrete poliovirus persistently, and the inability to know
      definitely that poliovirus has gone. As a result, there is uncertainty about if,
      when, and how we can end polio immunisation. In this article, we discuss several
      scenarios for the future of polio control. Because the emergence of cVDPVs
      necessitates discontinuing the use of live oral polio vaccine, we propose to
      strive towards a global coverage of near 100% vaccination against all major
      childhood infections using combination vaccines that contain inactivated
      poliovirus vaccine. Such a policy will present multiple challenges.

PMID- 17008174
TI  - Genetic susceptibility to infectious diseases: big is beautiful, but will bigger
      be even better?
AB  - Genetic epidemiology, including twin studies, provides robust evidence that
      genetic variation in human populations contributes to susceptibility to
      infectious disease. One of the major limitations of studies that attempt to
      identify the genes and mechanisms that underlie this susceptibility has been lack
      of power caused by small sample size. With the development of novel technologies,
      burgeoning information on the human genome, the HapMap project, and human genetic
      diversity, we are at the beginning of a new era in the study of the genetics of
      complex diseases. This review looks afresh at the epidemiological evidence that
      supports a role for genetics in susceptibility to infectious disease, examines
      the somewhat limited achievements to date, and discusses current advances in
      methodology and technology that will potentially lead to translational data in
      the future.

PMID- 17008189
TI  - What's new in Nicotine & Tobacco Research?

PMID- 17008190
TI  - Menstrual cycle phase effects on nicotine withdrawal and cigarette craving: a
      review.
AB  - Evidence suggests that women are less likely to quit smoking than are men. This
      may reflect differences in nicotine dependence and, more specifically perhaps,
      nicotine withdrawal and craving. However, there is conflicting research on gender
      differences on the experience of withdrawal and craving. Menstrual cycle effects
      may moderate this relationship. Given hormonal changes during the menstrual
      cycle, abstinence-related symptoms such as withdrawal and craving may vary as a
      function of menstrual phase as well. This qualitative review summarizes the
      modest but expanding body of research in this area. One of the challenges
      inherent in interpreting this literature is the difficulty in distinguishing
      withdrawal symptomatology from premenstrual symptomatology. Methodological
      variation, including limited sample size and possible selection bias, in which
      several studies finding null effects excluded women with severe premenstrual
      dysphoric disorder, may explain some of the inconsistent findings across studies.
      Nonetheless, some of the 13 studies included in this review found heightened
      experiences of withdrawal or craving within the latter days of the menstrual
      cycle (i.e., the luteal phase). Further research is necessary to replicate these
      findings, but they may suggest the need for focused cessation treatment during
      the luteal phase or quit attempts that are well timed relative to specific
      menstrual phases.

PMID- 17008191
TI  - Peer and parental influences on longitudinal trajectories of smoking among
      African Americans and Puerto Ricans.
AB  - The purpose of this study was to identify distinct trajectories of smoking
      behavior during a period extending from adolescence (mean age = 14 years) to
      young adulthood (mean age = 26 years) among African American and Puerto Rican
      adolescents/young adults, to examine ethnic and gender differences in group
      membership, and to assess the ability of peer and parental smoking to distinguish
      among trajectory groups. A community-based sample of 451 African American and
      Puerto Rican adolescents was interviewed four times during adolescence and in
      early adulthood, covering a span of 12 years. For both ethnic/racial groups, four
      distinct trajectories were identified: Nonsmokers, maturing-out smokers, late
      starting smokers, and early-starting continuous smokers. Compared with Puerto
      Ricans, African Americans were over-represented in the nonsmoking group, whereas
      Puerto Ricans were over-represented in the early-starting continuous group.
      Females were more likely than males to be early-starting continuous smokers than
      late starters. Adolescents who were exposed to peer and parental smoking in early
      adolescence were more likely to belong to trajectory groups characterized by
      higher levels of smoking. These findings show that exposure to peer and parental
      smoking in early adolescence constitutes a risk factor for engaging in elevated
      levels of smoking behavior at an early age and for continued smoking into
      adulthood for urban African Americans and Puerto Ricans. To be most effective,
      smoking prevention programs should address peer group and family influences on
      adolescent smoking.

PMID- 17008192
TI  - Expired carbon monoxide levels in self-reported smokers and nonsmokers in prison.
AB  - Breath carbon monoxide (CO) is a convenient, widely used method for abstinence
      validation, with cutoffs of 8-10 ppm commonly employed. The goal of the present
      study was to determine an appropriate CO cutoff to differentiate nonsmokers and
      smokers within a large sample (N = 374) of female prisoners incarcerated at a
      correctional facility in Virginia. Mean age of the population was 34.5 years,
      49.2% were White, and 29% had less than a high school education. Smoking
      prevalence was 74.1% within the prison population. Examination of CO levels
      versus smoking self-report using a receiver operator characteristic (ROC)
      analysis revealed that a CO cutoff of 3 ppm resulted in the best sensitivity
      (98.1%) and specificity (95.8%). Overall ROC area under the curve was 99% (95% CI
      = 98.2%-99.9%). This same cutoff was optimal for smoking subgroups including
      Black and light (<10 cigarettes/day) smokers. Results suggest that CO cutoffs
      higher than 3 ppm may misclassify some smokers as nonsmokers and underestimate
      the prevalence of smoking.

PMID- 17008193
TI  - Population effectiveness of pharmaceutical aids for smoking cessation: what is
      associated with increased success?
AB  - Although nicotine replacement therapy (NRT) has shown efficacy in randomized
      controlled trials, population effectiveness has appeared to diminish after it
      became available over the counter. The present study examined the population
      effectiveness of bupropion. It also examined whether population effectiveness of
      pharmaceutical-aid use in general (NRT, bupropion, or both) might be influenced
      by environmental factors: Having a smoke-free home (possible indication of
      motivation to quit) or no other smoker in the household. Data from the large
      population-based cross-sectional 1999 and 2002 California Tobacco Surveys were
      combined to improve statistical power for subgroup analyses of duration of
      abstinence following the most recent quit attempt in the past year. Moderate-to
      heavy daily smokers (at least 15 cigarettes/day) a year prior to the survey (N =
      2,640) were the main focus. A Cox proportional-hazards analysis suggested that
      bupropion was effective, perhaps even in the longer term. Further analyses
      identified significant interactions on abstinence duration between having a smoke
      free home and any pharmaceutical-aid use (NRT, bupropion, or both), and between
      having a smoke-free home and no other smoker in the household. Although
      pharmaceutical aids may have had a slight short-term benefit if the home was not
      smoke free, they appeared particularly effective if the home was smoke free, both
      in the short and longer term. The California population experience supports the
      policy that programs subsidizing pharmaceutical aids to help smokers quit
      (particularly bupropion, if appropriate) should target highly motivated smokers
      who have already taken a behavioral action, such as implementing a smoke-free
      home.

PMID- 17008194
TI  - Efficacy of naltrexone in smoking cessation: a preliminary study and an
      examination of sex differences.
AB  - This double-blinded, placebo-controlled trial evaluated the efficacy of
      naltrexone as an adjunct to standard smoking cessation treatment. Participants (N
      = 110) were adult male and female nicotine-dependent smokers who expressed
      interest in quitting smoking. All subjects received six sessions of behavioral
      counseling (1 hr/session for 6 weeks), and 1 month of the nicotine patch (21 mg
      for the first 2 weeks, 14 mg the third week, 7 mg the fourth week). Subjects were
      randomly assigned to the naltrexone or placebo group. The naltrexone group
      started at 25 mg daily for 3 days prior to the quit date, and increased to 50
      mg/day on the quit date and following 8 weeks. At the end of medication
      treatment, the naltrexone group had better quit rates versus the placebo group
      (48% quit on naltrexone vs. 41% on placebo), but this difference was not
      statistically significant. However, men and women differed on several measures:
      in the placebo group, women had significantly lower quit rates than men (39% vs.
      67%, p<.05), but in the naltrexone group, women had quit rates comparable with
      those of men (58% vs. 62%, p = ns). Further examination revealed that naltrexone
      significantly reduced men's and women's cessation-related weight gain and
      selectively reduced women's urge to smoke to relieve negative affect and
      withdrawal. The results suggest continued examination of naltrexone as an adjunct
      in smoking cessation, particularly in female smokers, who have historically shown
      worse outcomes with traditional treatment methods.

PMID- 17008195
TI  - Adolescent definitions of change in smoking behavior: an investigation.
AB  - Although adolescent smoking cessation has received increased research attention,
      little information exists as to how adolescents define change efforts for smoking
      behaviors. This issue is of particular importance because surveys routinely
      incorporate items assessing smoking cessation, yet how adolescents interpret such
      items is unclear. The present study investigated definitions of smoking behavior
      change efforts among adolescents. A total of 94 adolescent smokers-of average age
      16.7 years (SD = 1.0), 56% female, and 71% White-were asked to define the terms
      quit, stop, and cut down smoking. Responses to the three questions were
      categorized using content analysis. Definitions of quit and stop were categorized
      as (a) stop permanently, (b) stop temporarily, (c) stop except in certain
      situations, and (d) reduce smoking (for quit only). Definitions of cut down were
      categorized as (a) reduce the number of cigarettes, (b) smoke less in a time
      frame, (c) reduce smoking occasions, and (d) smoke less. Three trained raters
      sorted responses into each of the categories. Definitions of quit and stop were
      most frequently categorized in the stop permanently category (86% and 75%,
      respectively). Definitions of cut down were distributed across categories, with
      51% categorized as smoke less, 25% smoking less in a time frame, and 25% reducing
      number of cigarettes. Different definitions of stop were related to smoking
      history and motivation to quit, although the other two terms were not related to
      adolescent individual characteristics. Findings highlight the importance of using
      clearly defined questionnaire items when assessing adolescent smoking change
      efforts.

PMID- 17008196
TI  - Smoking cessation in homeless populations: a pilot clinical trial.
AB  - This study, which tested two motivational interviewing treatment approaches,
      assessed the feasibility of conducting a community-based smoking cessation
      intervention among homeless smokers. Participants (N = 46) were recruited from
      multiple facilities in the Kansas City area and were randomized to two counseling
      conditions in which they received five individual motivational interviewing
      sessions, six group meetings, and their choice of 8 weeks of 21-mg nicotine patch
      or 4-mg nicotine lozenge. The two counseling conditions consisted of motivational
      interviewing targeted either to smoking behaviors exclusively (smoking only) or
      to smoking and other addictions or life events that could affect ability to quit
      (smoking plus). Group meetings were designed to provide educational information
      and social support. Measures of feasibility assessed included the proportion of
      participants who returned for randomization among those eligible, adherence to
      prescribed nicotine replacement therapies, retention rates at the week 26 final
      study visit, and biochemically verified 7-day abstinence at week 26. Most
      participants (69.6%) chose nicotine patches, and 32% of those participants
      reported using at least four patches per week. Carbon monoxide verified 7-day
      abstinence rates in the smoking-only and smoking-plus groups were 13.04% and
      17.39% (ns), respectively, at week 8 and 8.70% and 17.39% (ns), respectively, at
      week 26. Participants who used at least four patches per week were more likely to
      have quit at 8 weeks than were those who used fewer patches (33.3% vs. 10.5%, p =
      .30). Results support the feasibility of conducting a smoking cessation
      intervention among homeless smokers. Findings also show promising effects for
      nicotine replacement therapy and counseling in this population. Developing
      programs to improve smoking cessation outcomes in underserved populations is an
      essential step toward achieving national health objectives and for ultimately
      reducing tobacco-related health disparities.

PMID- 17008197
TI  - Exposure to second-hand smoke air pollution assessed from bar patrons' urinary
      cotinine.
AB  - We used physical and pharmacokinetic modeling to estimate personal exposures to
      respirable particle (RSP) and carcinogenic particulate polycyclic aromatic
      hydrocarbon (PPAH) air pollution from second-hand smoke (SHS) from the increase
      in urinary cotinine of eight patrons of three bars in Bismarck, North Dakota. We
      compared SHS-RSP levels to the U.S. Air Quality Index (AQI), used to forecast
      outdoor air pollution conditions. We measured smoker density and air exchange
      rates to generalize our results. Urinary cotinine increased by an average of 4.28
      ng/ml to 6.88 ng/ml to 9.55 ng/ml above preexposure background from 6-hr
      exposures in the three bars. Corresponding estimated SHS-RSP levels were,
      respectively, 246 microg/m3, 396 microg/m3, and 549 microg/m3, comparable to
      those measured in 6 Wilmington, Delaware, bars and in 14 western New York bars.
      Estimated personal SHS-RSP air pollution exposures for the eight subjects, when
      converted to the 24-hr averaging time of the AQI, were "code red" (unhealthy).
      Measured outdoor air quality RSP levels for the same period were 1%-3% of the
      indoor RSP levels in the three bars, and were AQI "code green" (healthy).
      Estimated SHS-PPAH levels were comparable to peak 3-hr PPAH levels reported at a
      highway tollbooth. Bismarck cotinine-estimated SHS-RSP varied with smoker
      density, as did measured SHS-RSP levels in smoking bars in Delaware and New York.
      Our results show that smoking in bars produces levels of personal air pollution
      for bar patrons that merit air pollution alerts when sustained in the outdoor
      air.

PMID- 17008208
TI  - Introduction: Conditions for the emergence of life on the early Earth.

PMID- 17008209
TI  - The prebiotic molecules observed in the interstellar gas.
AB  - Over 130 molecules have been identified in the interstellar gas and circumstellar
      shells, the largest among them is a carbon chain with 13 atoms and molecular
      weight of 147 (twice that of the simplest amino acid glycine). The high
      reliability of astronomical identifications, as well as the fairly accurate
      quantitative analysis which can often be achieved, is emphasized. Glycine itself
      has been claimed, but a recent analysis indicates that few, if any, of the
      astronomical radio lines attributed to glycine are actually from that molecule.
      Polycyclic aromatic hydrocarbons (PAHs) have long been proposed as the source of
      the unidentified infrared bands between 3 and 16 microm, but no single PAH has
      been identified in space, partly because PAHs generally have weak or non-existent
      radio spectra. A remarkable exception is the non-planar corannulene molecule
      (C20H10) that has a strong radio spectrum; in the rich molecular cloud TMC-1, it
      is found that less than 10-5 of the carbon is contained in this molecule,
      suggesting that PAHs are not the dominant large molecules in the interstellar
      gas, as has been claimed. Owing to inherent spectroscopic limitations,
      determining the structures of the large molecules in space may require capture of
      the dust grains, which are continually entering the outer Solar System.

PMID- 17008210
TI  - Prebiotic materials from on and off the early Earth.
AB  - One of the greatest puzzles of all time is how did life arise? It has been
      universally presumed that life arose in a soup rich in carbon compounds, but from
      where did these organic molecules come? In this article, I will review proposed
      terrestrial sources of prebiotic organic molecules, such as Miller-Urey synthesis
      (including how they would depend on the oxidation state of the atmosphere) and
      hydrothermal vents and also input from space. While the former is perhaps better
      known and more commonly taught in school, we now know that comet and asteroid
      dust deliver tons of organics to the Earth every day, therefore this flux of
      reduced carbon from space probably also played a role in making the Earth
      habitable. We will compare and contrast the types and abundances of organics from
      on and off the Earth given standard assumptions. Perhaps each process provided
      specific compounds (amino acids, sugars, amphiphiles) that were directly related
      to the origin or early evolution of life. In any case, whether planetary, nebular
      or interstellar, we will consider how one might attempt to distinguish between
      abiotic organic molecules from actual signs of life as part of a robotic search
      for life in the Solar System.

PMID- 17008211
TI  - The carbon cycle on early Earth--and on Mars?
AB  - One of the goals of the present Martian exploration is to search for evidence of
      extinct (or even extant) life. This could be redefined as a search for carbon.
      The carbon cycle (or, more properly, cycles) on Earth is a complex interaction
      among three reservoirs: the atmosphere; the hydrosphere; and the lithosphere.
      Superimposed on this is the biosphere, and its presence influences the fixing and
      release of carbon in these reservoirs over different time-scales. The overall
      carbon balance is kept at equilibrium on the surface by a combination of tectonic
      processes (which bury carbon), volcanism (which releases it) and biology (which
      mediates it). In contrast to Earth, Mars presently has no active tectonic system;
      neither does it possess a significant biosphere. However, these observations
      might not necessarily have held in the past. By looking at how Earth's carbon
      cycles have changed with time, as both the Earth's tectonic structure and a more
      sophisticated biology have evolved, and also by constructing a carbon cycle for
      Mars based on the carbon chemistry of Martian meteorites, we investigate whether
      or not there is evidence for a Martian biosphere.

PMID- 17008212
TI  - Searching for signatures of life on Mars: an Fe-isotope perspective.
AB  - Recent spacecraft and lander missions to Mars have reinforced previous
      interpretations that Mars was a wet and warm planet in the geological past. The
      role of liquid water in shaping many of the surface features on Mars has long
      been recognized. Since the presence of liquid water is essential for survival of
      life, conditions on early Mars might have been more favourable for the emergence
      and evolution of life. Until a sample return mission to Mars, one of the ways of
      studying the past environmental conditions on Mars is through chemical and
      isotopic studies of Martian meteorites. Over 35 individual meteorite samples,
      believed to have originated on Mars, are now available for lab-based studies. Fe
      is a key element that is present in both primary and secondary minerals in the
      Martian meteorites. Fe-isotope ratios can be fractionated by low-temperature
      processes which includes biological activity. Experimental investigations of Fe
      reduction and oxidation by bacteria have produced large fractionation in Fe
      isotope ratios. Hence, it is considered likely that if there is/were any form of
      life present on Mars then it might be possible to detect its signature by Fe
      isotope studies of Martian meteorites. In the present study, we have analysed a
      number of Martian meteorites for their bulk-Fe-isotope composition. In addition,
      a set of terrestrial analogue material has also been analysed to compare the
      results and draw inferences. So far, our studies have not found any measurable Fe
      isotopic fractionation in bulk Martian meteorites that can be ascribed to any low
      temperature process operative on Mars.

PMID- 17008213
TI  - Physical conditions on the early Earth.
AB  - The formation of the Earth as a planet was a large stochastic process in which
      the rapid assembly of asteroidal-to-Mars-sized bodies was followed by a more
      extended period of growth through collisions of these objects, facilitated by the
      gravitational perturbations associated with Jupiter. The Earth's inventory of
      water and organic molecules may have come from diverse sources, not more than 10%
      roughly from comets, the rest from asteroidal precursors to chondritic bodies and
      possibly objects near Earth's orbit for which no representative class of
      meteorites exists today in laboratory collections. The final assembly of the
      Earth included a catastrophic impact with a Mars-sized body, ejecting mantle and
      crustal material to form the Moon, and also devolatilizing part of the Earth. A
      magma ocean and steam atmosphere (possibly with silica vapour) existed briefly in
      this period, but terrestrial surface waters were below the critical point within
      100 million years after Earth's formation, and liquid water existed continuously
      on the surface within a few hundred million years. Organic material delivered by
      comets and asteroids would have survived, in part, this violent early period, but
      frequent impacts of remaining debris probably prevented the continuous
      habitability of the Earth for one to several hundred million years. Planetary
      analogues to or records of this early time when life began include Io (heat
      flow), Titan (organic chemistry) and Venus (remnant early granites).

PMID- 17008214
TI  - Atmospheric composition and climate on the early Earth.
AB  - Oxygen isotope data from ancient sedimentary rocks appear to suggest that the
      early Earth was significantly warmer than today, with estimates of surface
      temperatures between 45 and 85 degrees C. We argue, following others, that this
      interpretation is incorrect-the same data can be explained via a change in
      isotopic composition of seawater with time. These changes in the isotopic
      composition could result from an increase in mean depth of the mid-ocean ridges
      caused by a decrease in geothermal heat flow with time. All this implies that the
      early Earth was warm, not hot.A more temperate early Earth is also easier to
      reconcile with the long-term glacial record. However, what triggered these early
      glaciations is still under debate. The Paleoproterozoic glaciations at
      approximately 2.4Ga were probably caused by the rise of atmospheric O2 and a
      concomitant decrease in greenhouse warming by CH4. Glaciation might have occurred
      in the Mid-Archaean as well, at approximately 2.9Ga, perhaps as a consequence of
      anti-greenhouse cooling by hydrocarbon haze. Both glaciations are linked to
      decreases in the magnitude of mass-independent sulphur isotope fractionation in
      ancient rocks. Studying both the oxygen and sulphur isotopic records has thus
      proved useful in probing the composition of the early atmosphere.

PMID- 17008215
TI  - Phosphorus in prebiotic chemistry.
AB  - The prebiotic synthesis of phosphorus-containing compounds-such as nucleotides
      and polynucleotides-would require both a geologically plausible source of the
      element and pathways for its incorporation into chemical systems on the primitive
      Earth. The mineral apatite, which is the only significant source of phosphate on
      Earth, has long been thought to be problematical in this respect due to its low
      solubility and reactivity. However, in the last decade or so, at least two
      pathways have been demonstrated which would circumvent these perceived problems.
      In addition, recent results would seem to suggest an additional, extraterrestrial
      source of reactive phosphorus. It appears that the 'phosphorus problem' is no
      longer the stumbling block which it was once thought to be.

PMID- 17008216
TI  - Transcription and translation in an RNA world.
AB  - The RNA world hypothesis requires a ribozyme that was an RNA-directed RNA
      polymerase (ribopolymerase). If such a replicase makes a reverse complementary
      copy of any sequence (including itself), in a simple RNA world, there is no
      mechanism to prevent self-hybridization. It is proposed that this can be avoided
      through the synthesis of a parallel complementary copy. The logical consequences
      of this are pursued and developed in a computer simulation, where the behaviour
      of the parallel copy is compared to the conventional reverse complementary copy.
      It is found that the parallel copy is more efficient at higher temperatures (up
      to 90 degrees C). A model for the ribopolymerase, based on the core of the large
      subunit (LSU) of the ribosome, is described. The geometry of a potential active
      site for this ribopolymerase suggests that it contained a cavity (now occupied by
      the aminoacyl-tRNA) and that an amino acid binding in this might have 'poisoned'
      the ribopolymerase by cross-reacting with the nucleoside-triphosphate before
      polymerization could occur. Based on a similarity to the active site components
      of the class-I tRNA synthetase enzymes, it is proposed that the amino acid could
      become attached to the nascent RNA transcript producing a variety of
      aminoacylated tRNA-like products. Using base-pairing interactions, some of these
      molecules might cross-link two ribopolymerases, giving rise to a precursor of the
      modern ribosome. A hybrid dimer, half polymerase and half proto-ribosome, could
      account for mRNA translocation before the advent of protein elongation factors.

PMID- 17008217
TI  - The origin of replicators and reproducers.
AB  - Replicators are fundamental to the origin of life and evolvability. Their
      survival depends on the accuracy of replication and the efficiency of growth
      relative to spontaneous decay. Infrabiological systems are built of two coupled
      autocatalytic systems, in contrast to minimal living systems that must comprise
      at least a metabolic subsystem, a hereditary subsystem and a boundary, serving
      respective functions. Some scenarios prefer to unite all these functions into one
      primordial system, as illustrated in the lipid world scenario, which is
      considered as a didactic example in detail. Experimentally produced chemical
      replicators grow parabolically owing to product inhibition. A selection
      consequence is survival of everybody. The chromatographized replicator model
      predicts that such replicators spreading on surfaces can be selected for higher
      replication rate because double strands are washed away slower than single
      strands from the surface. Analysis of real ribozymes suggests that the error
      threshold of replication is less severe by about one order of magnitude than
      thought previously. Surface-bound dynamics is predicted to play a crucial role
      also for exponential replicators: unlinked genes belonging to the same genome do
      not displace each other by competition, and efficient and accurate replicases can
      spread. The most efficient form of such useful population structure is
      encapsulation by reproducing vesicles. The stochastic corrector model shows how
      such a bag of genes can survive, and what the role of chromosome formation and
      intragenic recombination could be. Prebiotic and early evolution cannot be
      understood without the models of dynamics.

PMID- 17008218
TI  - Montmorillonite-catalysed formation of RNA oligomers: the possible role of
      catalysis in the origins of life.
AB  - Large deposits of montmorillonite are present on the Earth today and it is
      believed to have been present at the time of the origin of life and has recently
      been detected on Mars. It is formed by aqueous weathering of volcanic ash. It
      catalyses the formation of oligomers of RNA that contain monomer units from 2 to
      30-50. Oligomers of this length are formed because this catalyst controls the
      structure of the oligomers formed and does not generate all possible isomers.
      Evidence of sequence-, regio- and homochiral selectivity in these oligomers has
      been obtained. Postulates on the role of selective versus specific catalysts on
      the origins of life are discussed. An introduction to the origin of life is given
      with an emphasis on reaction conditions based on the recent data obtained from
      zircons 4.0-4.5Ga.

PMID- 17008219
TI  - From volcanic origins of chemoautotrophic life to Bacteria, Archaea and Eukarya.
AB  - The theory of a chemoautotrophic origin of life in a volcanic iron-sulphur world
      postulates a pioneer organism at sites of reducing volcanic exhalations. The
      pioneer organism is characterized by a composite structure with an inorganic
      substructure and an organic superstructure. Within the surfaces of the inorganic
      substructure iron, cobalt, nickel and other transition metal centres with
      sulphido, carbonyl and other ligands were catalytically active and promoted the
      growth of the organic superstructure through carbon fixation, driven by the
      reducing potential of the volcanic exhalations. This pioneer metabolism was
      reproductive by an autocatalytic feedback mechanism. Some organic products served
      as ligands for activating catalytic metal centres whence they arose. The unitary
      structure-function relationship of the pioneer organism later gave rise to two
      major strands of evolution: cellularization and emergence of the genetic
      machinery. This early phase of evolution ended with segregation of the domains
      Bacteria, Archaea and Eukarya from a rapidly evolving population of pre-cells.
      Thus, life started with an initial, direct, deterministic chemical mechanism of
      evolution giving rise to a later, indirect, stochastic, genetic mechanism of
      evolution and the upward evolution of life by increase of complexity is grounded
      ultimately in the synthetic redox chemistry of the pioneer organism.

PMID- 17008220
TI  - Self-assembly processes in the prebiotic environment.
AB  - An important question guiding research on the origin of life concerns the
      environmental conditions where molecular systems with the properties of life
      first appeared on the early Earth. An appropriate site would require liquid
      water, a source of organic compounds, a source of energy to drive polymerization
      reactions and a process by which the compounds were sufficiently concentrated to
      undergo physical and chemical interactions. One such site is a geothermal
      setting, in which organic compounds interact with mineral surfaces to promote
      self-assembly and polymerization reactions. Here, we report an initial study of
      two geothermal sites where mixtures of representative organic solutes (amino
      acids, nucleobases, a fatty acid and glycerol) and phosphate were mixed with high
      temperature water in clay-lined pools. Most of the added organics and phosphate
      were removed from solution with half-times measured in minutes to a few hours.
      Analysis of the clay, primarily smectite and kaolin, showed that the organics
      were adsorbed to the mineral surfaces at the acidic pH of the pools, but could
      subsequently be released in basic solutions. These results help to constrain the
      range of possible environments for the origin of life. A site conducive to self
      assembly of organic solutes would be an aqueous environment relatively low in
      ionic solutes, at an intermediate temperature range and neutral pH ranges, in
      which cyclic concentration of the solutes can occur by transient dry intervals.

PMID- 17008221
TI  - Early anaerobic metabolisms.
AB  - Before the advent of oxygenic photosynthesis, the biosphere was driven by
      anaerobic metabolisms. We catalogue and quantify the source strengths of the most
      probable electron donors and electron acceptors that would have been available to
      fuel early-Earth ecosystems. The most active ecosystems were probably driven by
      the cycling of H2 and Fe2+ through primary production conducted by anoxygenic
      phototrophs. Interesting and dynamic ecosystems would have also been driven by
      the microbial cycling of sulphur and nitrogen species, but their activity levels
      were probably not so great. Despite the diversity of potential early ecosystems,
      rates of primary production in the early-Earth anaerobic biosphere were probably
      well below those rates observed in the marine environment. We shift our attention
      to the Earth environment at 3.8Gyr ago, where the earliest marine sediments are
      preserved. We calculate, consistent with the carbon isotope record and other
      considerations of the carbon cycle, that marine rates of primary production at
      this time were probably an order of magnitude (or more) less than today. We
      conclude that the flux of reduced species to the Earth surface at this time may
      have been sufficient to drive anaerobic ecosystems of sufficient activity to be
      consistent with the carbon isotope record. Conversely, an ecosystem based on
      oxygenic photosynthesis was also possible with complete removal of the oxygen by
      reaction with reduced species from the mantle.

PMID- 17008222
TI  - Hyperthermophiles in the history of life.
AB  - Today, hyperthermophilic ('superheat-loving') bacteria and archaea are found
      within high-temperature environments, representing the upper temperature border
      of life. They grow optimally above 80 degrees C and exhibit an upper temperature
      border of growth up to 113 degrees C. Members of the genera, Pyrodictium and
      Pyrolobus, survive at least 1h of autoclaving. In their basically anaerobic
      environments, hyperthermophiles (HT) gain energy by inorganic redox reactions
      employing compounds like molecular hydrogen, carbon dioxide, sulphur and ferric
      and ferrous iron. Based on their growth requirements, HT could have existed
      already on the early Earth about 3.9Gyr ago. In agreement, within the
      phylogenetic tree of life, they occupy all the short deep branches closest to the
      root. The earliest archaeal phylogenetic lineage is represented by the extremely
      tiny members of the novel kingdom of Nanoarchaeota, which thrive in submarine hot
      vents. HT are very tough survivors, even in deep-freezing at -140 degrees C.
      Therefore, during impact ejecta, they could have been successfully transferred to
      other planets and moons through the coldness of space.

PMID- 17008223
TI  - The origin and emergence of life under impact bombardment.
AB  - Craters formed by asteroids and comets offer a number of possibilities as sites
      for prebiotic chemistry, and they invite a literal application of Darwin's 'warm
      little pond'. Some of these attributes, such as prolonged circulation of heated
      water, are found in deep-ocean hydrothermal vent systems, previously proposed as
      sites for prebiotic chemistry. However, impact craters host important
      characteristics in a single location, which include the formation of diverse
      metal sulphides, clays and zeolites as secondary hydrothermal minerals (which can
      act as templates or catalysts for prebiotic syntheses), fracturing of rock during
      impact (creating a large surface area for reactions), the delivery of iron in the
      case of the impact of iron-containing meteorites (which might itself act as a
      substrate for prebiotic reactions), diverse impact energies resulting in
      different rates of hydrothermal cooling and thus organic syntheses, and the
      indiscriminate nature of impacts into every available lithology-generating large
      numbers of 'experiments' in the origin of life. Following the evolution of life,
      craters provide cryptoendolithic and chasmoendolithic habitats, particularly in
      non-sedimentary lithologies, where limited pore space would otherwise restrict
      colonization. In impact melt sheets, shattered, mixed rocks ultimately provided
      diverse geochemical gradients, which in present-day craters support the growth of
      microbial communities.

PMID- 17008224
TI  - Implications of a 3.472-3.333 Gyr-old subaerial microbial mat from the Barberton
      greenstone belt, South Africa for the UV environmental conditions on the early
      Earth.
AB  - Modelling suggests that the UV radiation environment of the early Earth, with DNA
      weighted irradiances of about three orders of magnitude greater than those at
      present, was hostile to life forms at the surface, unless they lived in specific
      protected habitats. However, we present empirical evidence that challenges this
      commonly held view. We describe a well-developed microbial mat that formed on the
      surface of volcanic littoral sediments in an evaporitic environment in a 3.5
      3.3Ga-old formation from the Barberton greenstone belt. Using a multiscale,
      multidisciplinary approach designed to strongly test the biogenicity of potential
      microbial structures, we show that the mat was constructed under flowing water by
      0.25 microm filaments that produced copious quantities of extracellular polymeric
      substances, representing probably anoxygenic photosynthesizers. Associated with
      the mat is a small colony of rods-vibroids that probably represent sulphur
      reducing bacteria. An embedded suite of evaporite minerals and desiccation cracks
      in the surface of the mat demonstrates that it was periodically exposed to the
      air in an evaporitic environment. We conclude that DNA-damaging UV radiation
      fluxes at the surface of the Earth at this period must either have been low
      (absorbed by CO2, H2O, a thin organic haze from photo-dissociated CH4, or SO2
      from volcanic outgassing; scattered by volcanic, and periodically, meteorite
      dust, as well as by the upper layers of the microbial mat) and/or that the micro
      organisms exhibited efficient gene repair/survival strategies.

PMID- 17008225
TI  - Conditions for the emergence of life on the early Earth: summary and reflections.
AB  - This review attempts to situate the emergence of life on the early Earth within
      the scientific issues of the operational and mechanistic description of life, the
      conditions and constraints of prebiotic chemistry, together with bottom-up
      molecular fabrication and biomolecular nanofabrication and top-down
      miniaturization approaches to the origin of terrestrial life.

PMID- 17008226
TI  - A 10-year follow-up study of penicillin-non-susceptible S. pneumoniae during an
      intervention programme in Malmo, Sweden.
AB  - Changes in the proportion of penicillin-non-susceptible Streptococcus pneumoniae
      (PNSP) isolates during an intervention programme were evaluated by phenotypic
      analysis of all initial isolates with penicillin MIC > or =0.5 microg/ml (n=1248)
      collected 1995-2004. During the study period, the proportion of such isolates was
      fairly constant (12-19%), and there was no statistically significant variation in
      the proportion of total PNSP cases (MIC > or =0.12 microg/ml) or PNSP with MIC >
      or =0.5 microg/ml, with the exception of an increase in 2004. Analysis restricted
      to clinical cases revealed no statistically significant changes. 23 different
      serogroups were found, and serogroup 9 isolates accounted for almost half of the
      PNSP cases. Only minor changes in phenotypic characteristics occurred in the
      other serogroups, which indicates that the increase in PNSP in 2004 was not due
      to import of a new resistant clone. Antibiotic consumption is considered to be an
      important risk factor for penicillin resistance in S. pneumoniae. After
      initiation of the intervention programme in Malmo, overall prescribing of
      antibiotics decreased 28%, and the reduction was even greater among children
      (52%). In conclusion, the proportion of PNSP isolates in Malmo has remained
      stable, despite the intervention programme and decreased consumption of
      antibiotics.

PMID- 17008227
TI  - Leptospirosis in Istanbul, Turkey: a wide spectrum in clinical course and
      complications.
AB  - Patients with high fever and multiorgan involvement were investigated for the
      determination of frequency, clinical course and complications of leptospirosis in
      Istanbul. Leptospirosis was determined in 22 cases among the 35 hospitalized
      patients that were pre-diagnosed as leptospirosis according to 'Probable
      Leptospirosis Diagnosis and Follow-up' form. Among the leptospirosis cases 19
      were male and 16 were military staff. Mean age was 35.6 y. Dark field examination
      (DFE), latex agglutination test (LAG), ELISA IgM, leptospirosis culture (LC) and
      microscopic agglutination test (MAT) were performed to confirm the diagnoses. The
      most frequent initial symptoms and findings were fever, fatigue, headache, nausea
      vomiting and increased muscle sensitivity. Jaundice was noted only in 2 cases. A
      74-y-old female patient died after the recurrence of the disease with severe
      rhabdomyolysis and pulmonary failure. Sagittal sinus thrombosis, perimyocarditis
      and chronic renal failure were major complications in another 3 patients. ELISA
      IgM, LC, DFE, LAG and MAT tests were positive in 68, 72, 82, 100 and 100% of the
      patients, respectively. As a conclusion, diagnosis of leptospirosis is usually
      overlooked. Clinical awareness, use of probable leptospirosis diagnosis forms and
      the application of different laboratory methods in the diagnosis of suspected
      cases may offer the chance to diagnose the leptospirosis accurately.

PMID- 17008228
TI  - In vitro activities of three carbapenems against recent bacterial isolates from
      severely ill patients at Swedish hospitals.
AB  - To study the in vitro activity of imipenem, meropenem and ertapenem against
      common pathogens isolated from patients in intensive care, haematology and
      dialysis/nephrology units at 7 Swedish university hospitals, a total of 788
      isolates were collected during 2002-2003. The distribution of the isolates was as
      follows: Escherichia coli (n = 140), Klebsiella spp. (n = 132), Proteus spp. (n =
      97), Enterobacter spp. (n = 113), Pseudomonas aeruginosa (n = 126), Acinetobacter
      spp. (n = 53) and Enterococcus faecalis (n = 127). The susceptibility to the 3
      carbapenems was determined by E-test, and the MICs were interpreted according to
      SRGA criteria. All 3 carbapenems were highly active against Enterobacteriaceae.
      The overall susceptibility to imipenem, meropenem and ertapenem was 90%, 98% and
      93%, respectively. Against Enterobacteriaceae, Enterobacter spp. excluded,
      ertapenem had an equal or lower MIC(90) than meropenem. Apart from being the most
      active carbapenem against Enterobacteriaceae, meropenem was also the most active
      carbapenem against P. aeruginosa, whereas imipenem was the most active drug
      against Acinetobacter spp. The carbapenems are still potent antibiotics. With the
      introduction of ertapenem, and an expected increase in the carbapenem consumption
      due to an increased prevalence of strains with extended-spectrum beta-lactamases,
      continuous surveillance of carbapenem resistance appears to be warranted, with
      special attention to P. aeruginosa, Enterobacter and Proteus spp.

PMID- 17008229
TI  - Adverse outcomes in patients with community acquired pneumonia discharged with
      clinical instability from Internal Medicine Department.
AB  - There are well established admission criteria for patients suffering from
      community-acquired pneumonia, yet the clinical tool for decision to discharge the
      hospitalized patient is lacking. Continuous pressure to reduce hospital
      expenditures can lead to a premature discharge of unstable patients. The current
      study assessed the impact of clinical instability at discharge on short-term
      outcomes. Demographic data, background disease, laboratory tests results and PORT
      score were assessed prospectively. On the last day of the hospitalization 7
      physiological parameters of instability were evaluated. 60 d composite mortality
      and readmission rate was a primary outcome measure. Of the 373 patients, 22% were
      discharged with 1 or more instabilities, of whom 26.8% reached primary outcome
      within 60 d, compared to 8.2% of patients with no instabilities. 60 d death rate
      was 2.1% in the former group, compared to 14.6% in the unstable patients
      (p<0.001). Instability on discharge remained a significant prognosticator of
      adverse outcome (odds ratio 3.5; 95% CI 1.8-6.8) after adjustment for pneumonia
      severity and baseline comorbidity. We concluded that discharging an unstable
      patient hospitalized with pneumonia is associated with elevated risk of death or
      readmission within 60 d. Pneumonia guidelines should include objective criteria
      for judging patients' stability and promptness for discharge.

PMID- 17008230
TI  - Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis:
      prognostic value of TIMP-1 in severe sepsis.
AB  - The enzyme group of matrix metalloproteinases (MMPs) and their inhibitors, so
      called tissue inhibitors of matrix-metalloproteinases (TIMPs), are crucial
      mediators responsible for wound repair after parenchymal damage. Little is known
      about the role of MMPs and TIMPs in severe sepsis. The aim of the present study
      was therefore to investigate their levels in patients with severe sepsis and to
      examine their association with prognosis. MMP-2, MMP-9, TIMP-1, TIMP-2 and
      interleukin-6 (IL-6) plasma levels were measured by ELISA methods in 37 patients
      on day 1 of severe sepsis. 37 healthy volunteers served as controls. Levels of
      MMP-9, TIMP-1, TIMP-2 and IL-6 in septic patients were significantly higher
      compared to healthy controls (p<0.001), whereas MMP-2 levels were not different
      in patients and controls. TIMP-1 levels were significantly higher in non
      survivors (4675+/-435 ng/ml, mean+/-SEM) compared to survivors of severe sepsis
      (3201+/-249 ng/ml; p<0.01). Septic patients with TIMP-1 values >3200 ng/ml were
      4.5 times more likely to die than patients with lower values (RR = 4.5; 95% CI
      1.14-17.6, p = 0.014). Our results indicate that MMP-9, TIMP-2 and TIMP-1 are
      elevated in severe sepsis. Furthermore, TIMP-1 may serve as a useful laboratory
      marker to predict the clinical outcome of patients presenting with severe sepsis.

PMID- 17008231
TI  - Native-valve infective endocarditis caused by Enterobacteriaceae: report on 9
      cases and literature review.
AB  - Although the demographic characteristics of patients who develop infective
      endocarditis (IE) have changed over the last few decades, Enterobacteriaceae
      remain rarely responsible. We report the clinical and epidemiological
      characteristics of 9 patients with native-valve Enterobacteriaceae IE from 6
      French medical intensive care units over a 10-y period and have identified 29
      additional cases in the literature. Nearly a third of the 38 patients were
      immunocompromised and/or had previously known valvular heart disease. Salmonella
      spp. and Yersinia spp. were the most frequently isolated microorganisms reported
      in the literature. The overall mortality rate was 24% (9/38) and was lower for
      operated patients (10% (1/10)) compared to those who did not undergo valve
      surgery (31% (8/26)). Our results confirmed the rarity of native-valve
      endocarditis caused by Enterobacteriaceae, pathogens frequently responsible for
      nosocomial and community-acquired bacteraemias. This paradox may be explained by
      susceptibility to the bactericidal action of serum and the inability of these
      bacteria to colonize the endocardium.

PMID- 17008232
TI  - Routes of M. tuberculosis transmission among merchant seafarers.
AB  - For centuries, tuberculosis has been identified as a burden to seafarers. In this
      study, we assessed the magnitude of tuberculosis among merchant seafarers today.
      Furthermore, we identified the most likely routes of M. tuberculosis transmission
      by the use of DNA fingerprinting. A database containing all culture-positive
      tuberculosis cases in Denmark in 1992-2003 was combined with a register on all
      seafarers and their employment periods aboard Danish ships. All strains of M.
      tuberculosis were analysed using DNA-subtyping. 64 cases of culture positive
      tuberculosis among seafarers were identified. The risk of tuberculosis among
      males was 1.51 (1.10-2.01) compared with the general population. Two of the 64
      cases were likely to be shipping-related, 5 were possibly shipping-related, and
      10 were less likely to be shipping-related. The remaining 47 cases were very
      unlikely to be shipping related. Including the 2 first categories, the incidence
      was 0.09 cases per 1000 y at sea. The excess risk of tuberculosis among active
      and former Danish seafarers is most probably due to infections acquired in
      Denmark. Despite multi-cultural crews aboard, including many from high-incidence
      countries, our study indicates that only limited transmission of M. tuberculosis
      takes place among crew aboard modern ships or during shore leaves.

PMID- 17008233
TI  - The throat: an important site for MRSA colonization.
AB  - In order to evaluate the value of bacterial cultures taken from the throat, 266
      patients with MRSA were retrospectively assessed. At the time when MRSA was first
      detected in the patient, the most frequent sites positive for MRSA were a skin
      lesion (110 patients, 41%), the anterior nares (109 patients, 41%), and the
      throat (102 patients, 38%). In 26%, 17%, and 17% of the patients, a skin lesion,
      the anterior nares, and the throat, respectively, were the only site where MRSA
      was seen. In 123 patients cultured for MRSA because of a close contact with an
      already known MRSA patient, 65 patients (53%) were positive for MRSA in their
      throat and in 40 patients (33%), throat was the only sample site with MRSA at the
      time when the patient was found to be MRSA positive. 146 of the 266 patients
      (55%) were colonized with MRSA in the throat any time throughout the period they
      were MRSA positive. We conclude that throat is an important reservoir for MRSA
      and that samples taken from the throat should be included in screening patients
      for MRSA.

PMID- 17008234
TI  - Lack of correlation between nutritional status and seroprotection against
      influenza in a long term care facility.
AB  - We conducted a prospective study in a long-term care facility. Virologic
      diagnosis was assessed using viral isolation, polymerase chain reaction and
      serology for all patients with a flu-like syndrome. Albumin, vitamins and trace
      elements were also measured. RESULTS: The risk of influenza increased 6.5-fold in
      patients with an antibody titer of 40 during the influenza outbreak (P=0.04).
      Micronutrients and vitamins deficiencies were important. Patients with antibody
      titer >1:40 could still be infected by the virus without correlation with the
      nutritional status. CONCLUSION: Humoral protection with a titer >1:40 might not
      be protective in the elderly. Nutritional deficiencies were too prevalent to
      detect any effect on the results.

PMID- 17008235
TI  - The clinical and laboratory survey of Iranian patients with hyper-IgE syndrome.
AB  - In order to determine the clinical and laboratory findings of Iranian patients
      with presumed hyper-immunoglobulin E syndrome (HIES), the medical records of 22
      patients from 21 unrelated families, who had been registered in the Iranian
      Primary Immunodeficiency Registry, were observed. The median age of patients at
      the time of first symptom and at the time of diagnosis was 1 month and 52.5
      months, respectively, with a median diagnosis delay of 70 months. 13 families had
      consanguineous marriages. IgE level was higher than 2000 IU/ml in all patients,
      ranging from >2000 to 80,000 IU/ml. The most commonly occurring manifestations
      were: eczema and dermatitis, pneumonia, upper respiratory tract infections,
      cutaneous abscesses, diarrhoea, deep abscesses, and otitis media. Other less
      frequent manifestations were: mucocutaneous candidiasis, sinusitis, cutaneous
      ulcers, Molluscum contagiosum, herpetic keratitis, onychomycosis, conjunctivitis,
      septic arthritis, and meningitis. Five patients were complicated by
      bronchiectasis due to recurrent pneumonia and 5 patients died because of severe
      infections and malignancy. The HIES is a multisystem disorder that affects
      especially cutaneous, respiratory, skeletal and the immune system. Although HIES
      is a rare condition, the recurrent infections should always raise a suspicion,
      which deserves further evaluation for detecting the syndrome.

PMID- 17008236
TI  - Moxifloxacin distribution in the interstitial space of infected decubitus ulcer
      tissue of patients with spinal cord injury measured by in vivo microdialysis.
AB  - We investigated the distribution of moxifloxacin in the interstitial space of
      normal and infected subcutaneous tissue in patients with spinal cord injury and
      decubitus ulcers using in vivo microdialysis. Drug concentrations achieved in
      serum, saliva, normal and infected tissues showed approximately parallel time
      profiles. The interstitial tissue fluids reached bactericidal levels for common
      bacteria found in infected skin lesions. Our findings suggest that moxifloxacin
      exhibits good and similar penetration into the interstitial space fluid in normal
      subcutaneous tissue and infected decubitus ulcers in patients with spinal cord
      injury.

PMID- 17008237
TI  - Monocytes as a site of production of soluble triggering receptor expressed on
      myeloid cells-1 (sTREM-1) in the septic host.
AB  - The role of blood monocytes in the secretion of soluble triggering receptor
      expressed on myeloiod cells (sTREM-1) was studied in 90 patients with septic
      syndrome due to ventilator-associated pneumonia. Blood monocytes were isolated on
      7 consecutive d after initiation of symptoms. Monocytes were incubated in the
      absence or presence of LPS and concentrations of sTREM-1 and TNFalpha in cell
      supernatants and serum were estimated by an enzyme-immunoassay. sTREM-1 and
      TNFalpha were consistently present at detectable levels in the cell supernatants.
      LPS induced increased levels of TNFalpha but not of sTREM-1. Supernatants
      recovered from monocytes on d 1 showed levels of sTREM-1 higher than those
      recovered on any of the following 6 d (p<0.05); these levels were higher in non
      survivors than in survivors. Supernatants recovered from monocytes on d 1 of
      patients with severe sepsis had elevated concentrations of sTREM-1 compared to
      patients with septic shock and similar to patients with sepsis. A negative
      correlation was found between levels of sTREM-1 in the cell supernatants and the
      percentage of apoptotic monocytes. In essence, the above results suggest that
      monocytes contribute to the production of sTREM-1 in the event of septic
      syndrome.

PMID- 17008238
TI  - Native valve Aspergillus endocarditis in two patients with aplastic anaemia.
AB  - Native valve fungal endocarditis is an uncommon disease with a high mortality
      rate. We present the clinical features, histological findings and outcome of 2
      patients with native valve Aspergillus endocarditis. Both patients had aplastic
      anaemia as a predisposing disease. The diagnosis was made by Duke's criteria in 1
      case and by histology in the other. Surgery was precluded owing to profound
      thrombocytopenia. Both patients had fatal outcome despite administration of
      liposomal amphotericin beta.

PMID- 17008239
TI  - Enhanced chickenpox exanthema in vaccine injection site.
AB  - Exacerbation of viral exanthema has been described after different types of
      aggression. We report a case of enhanced chickenpox exanthema occurring in the
      vaccination site of an otherwise healthy boy. Specific local inflammatory
      modifications may explain the increased number of varicella skin lesions on the
      site of a previous vaccine-induced inflammation.

PMID- 17008241
TI  - The influence of antimicrobial therapy on the sensitivity of Legionella PCR.
AB  - The aim of our study was to establish the sensitivity of Legionella DNA detection
      in lower respiratory tract samples in 3 cases of Legionnaires' disease after
      initiation of specific antibiotic therapy. The results showed that Legionella
      amplicon intensity was highest in the sputum or bronchial aspirates collected at
      or before the start of appropriate therapy and decreased markedly within 3 days
      of therapy. PCR testing was negative within 4 to 6 days of therapy. These data
      suggest that within a few days specific antimicrobial therapy induces a
      significant drop of bacterial concentration in respiratory secretions reaching
      the detection limit of PCR assay. Respiratory samples for Legionella PCR should
      be obtained before or early after initiating antimicrobial therapy.

PMID- 17008240
TI  - Multiple opportunistic infections after high-dose steroid therapy for giant cell
      arteritis in a patient previously treated with a purine analog.
AB  - We present the case of a 74-y-old HIV-negative female who suffered simultaneously
      from multiple opportunistic infections and a Klebsiella pneumoniae sepsis during
      high-dose steroids for giant cell arteritis. The patient was treated with a
      purine analog due to hairy cell leukaemia 10 y previously. Purine analog therapy
      can lead to long lasting defects in cell-mediated immunity. In these patients,
      treatment with steroids should be closely monitored with CD4 counts.

PMID- 17008242
TI  - Fulminant varicella hepatitis in a human immunodeficiency virus infected patient:
      case report and review of the literature.
AB  - We report the case of a 35-y-old HIV-infected female, who presented fulminant
      varicella hepatitis and recovered under medical treatment. Varicella zoster virus
      is an uncommon cause of acute liver disease which occurs mainly in
      immunocompromised patients. Acyclovir is the cornerstone of the treatment.

PMID- 17008243
TI  - DNA sequence-based detection of group B Streptococcus directly from heart valve
      tissue in a patient with culture-negative endocarditis.
AB  - A human case of culture-negative bacterial endocarditis is presented where
      conventional methods failed to determine a microbial aetiology. DNA sequencing
      performed directly on autopsy heart valve tissue revealed Streptococcus
      agalactiae (group B streptococcus). To our knowledge, this is the first report of
      DNA sequence-based detection of this organism directly from a heart valve.

PMID- 17008244
TI  - Hip arthroplasty infection with heterogeneous vancomycin-resistant Staphylococcus
      aureus.
AB  - We report a case of heterogeneous vancomycin-resistant Staphylococcus aureus hip
      arthroplasty infection. Apparent cure was obtained by excision of infected
      tissues and removal of prosthetic material combined with optimal and closely
      monitored prolonged intravenous antibiotic therapy including continuous high-dose
      vancomycin.

PMID- 17008245
TI  - Abiotrophia defectiva: a rare cause of infective endocarditis.
AB  - A case of Abiotrophia defectiva-caused infective endocarditis is described. The
      patient was successfully treated with penicillin combined with gentamicin. Due to
      the fastidious nature of the agent, there is a need for special media for
      isolation and moreover, there is a need for a future development of
      susceptibility assays applicable to the organism.

PMID- 17008246
TI  - Multiphasic encephalomyelitis in a patient with recurrent herpes simplex type 2
      meningitis.
AB  - We here describe a patient with a history of recurrent HSV-2 meningitis who had
      been free from symptoms for almost 20 y when he developed an acute
      encephalomyelitis. The clinical course laboratory and radiological findings
      support an acute multiphasic disseminated encephalomyelitis induced by a
      recurrent HSV-2 infection.

PMID- 17008247
TI  - Acute pulmonary aspergillosis in immunocompetent subjects after exposure to bark
      chippings.
AB  - We describe 2 cases of immunocompetent males with acute community-acquired
      invasive pulmonary aspergillosis developing shortly after spreading bark
      chippings. One patient with a fatal outcome was initially diagnosed as allergic
      alveolitis rather than infection and received steroid treatment illustrating the
      obvious challenges in the differential diagnosis between these disease entities.

PMID- 17008248
TI  - Severe Candida albicans panophthalmitis treated with all available and
      potentially effective antifungal drugs: fluconazole, liposomal amphotericin B,
      caspofungin, and voriconazole.
AB  - A severe case of Candida albicans panophthalmitis, probably prompted by an
      underlying diabetes mellitus, is reported. The course was prolonged (more than 16
      weeks), although favourable after treatment with several antifungal agents, all
      with a predictable activity in this ocular complication and with proven
      susceptibility in the present case: fluconazole, liposomal amphotericin B,
      caspofungin, and voriconazole.

PMID- 17008250
TI  - Collaborative planning and situation awareness in Army command and control.
AB  - We conducted a theoretical investigation of a complex command and control (C2)
      operation--the manoeuvres planning processes in Army land-battle situations, to
      improve understanding of how technology can best be designed to support planning
      and course of action development. We drew upon results from cognitive task
      analyses and interviews with subject matter experts and insights gleaned from
      observations of Army training exercises and experiments to make inferences on the
      C2 activities carried out in preparation for tactical manoeuvres. In this paper,
      we summarize several critical human factors issues associated with planning in a
      rapidly evolving environment, as identified in our investigation, and describe
      system design concepts aimed at addressing these challenges to distributed
      collaborative planning of C2 activities. We conclude with implications for the
      application of these findings to other C2 domains.

PMID- 17008251
TI  - Effects of battlefield display frames of reference on navigation tasks, spatial
      judgements, and change detection.
AB  - This paper describes an experiment which illustrates the cause of 'cognitive
      tunnelling' as it affects information gathering and perception-based task
      performance in computer-generated terrain displays of varying frames of
      reference. Cognitive tunnelling refers to the effect where observers focus
      attention on information from specific areas of a display to the exclusion of
      information presented outside these areas. Previous research suggests that
      cognitive tunnelling is induced by more immersive or egocentric visual displays.
      Results from our preceding study suggested that an immersed split-screen display
      induces cognitive tunnelling and results in poorer information extraction and
      situation awareness than an exocentric display of the same information. The
      current study determined that failure of the observers to integrate information
      across the two views of the immersed display led to the cognitive tunnelling
      effect. Cognitive tunnelling was also affected by primacy of information
      initially presented within the larger egocentric view in the immersed display.

PMID- 17008252
TI  - Understanding emergency medical dispatch in terms of distributed cognition: a
      case study.
AB  - Emergency medical dispatch (EMD) is typically a team activity, requiring fluid
      coordination and communication between team members. Such working situations have
      often been described in terms of distributed cognition (DC), a framework for
      understanding team working. DC takes account of factors such as shared
      representations and artefacts to support reasoning about team working. Although
      the language of DC has been developed over several years, little attention has
      been paid to developing a methodology or reusable representation which supports
      reasoning about an interactive system from a DC perspective. We present a case
      study in which we developed a method for constructing a DC account of team
      working in the domain of EMD, focusing on the use of the method for describing an
      existing EMD work system, identifying sources of weakness in that system, and
      reasoning about the likely consequences of redesign of the system. The resulting
      DC descriptions have yielded new insights into the design of EMD work and of
      tools to support that work within a large EMD centre.

PMID- 17008253
TI  - Command and control in emergency services operations: a social network analysis.
AB  - There is increasing interest in the use of social network analysis as a tool to
      study the performance of teams and organizations. In this paper, processes of
      command and control in the emergency services are explored from the perspective
      of social network theory. We report a set of network analyses (comprising
      visualization, a selection of mathematical metrics, and a discussion of
      procedures) based on the observation of six emergency service incidents: three
      fire service operations involving the treatment of hazardous chemicals, and three
      police operations involving immediate response to emergency calls. The findings
      are discussed in terms of our attempts to categorize the network structures
      against a set of extant command and control network archetypes and the
      relationship between those structures; comments on the qualities the networks
      display are put into the contexts of the incidents reported. We suggest that
      social network analysis may have a valuable part to play in the general study of
      command and control.

PMID- 17008254
TI  - Speech acts, communication problems, and fighter pilot team performance.
AB  - Two aspects of team communication, speech acts and communication problems, and
      their relation to team performance in a team air combat simulator were studied.
      The purpose was to enhance the understanding of how team performance is related
      to team communication. Ten Swedish fighter pilots and four fighter controllers of
      varying experience participated. Data were collected during fighter simulator
      training involving four pilots and one fighter controller in each of two teams.
      Speech acts were collapsed over seven categories and communication problems over
      five categories. Communication was studied from two perspectives: critical
      situation outcome and mission outcome. Some problems were closely related to
      particular speech acts. Speech act frequency, especially meta-communications and
      tactics, was highest when winning. However, the timing of tactics in critical
      situations needs further research. Communication problem frequency was highest
      for runs which ended equally. The most common problem was simultaneous speech,
      possibly because of the simulator radio system. The number of speech acts was
      related to enhanced performance but in a complex manner. Thus in order to work
      efficiently team members need to communicate, but to communicate sufficiently and
      at appropriate times. This work has applications for fighter pilot and controller
      team training and the development of communication standards.

PMID- 17008255
TI  - Cognitive task load in a naval ship control centre: from identification to
      prediction.
AB  - Deployment of information and communication technology will lead to further
      automation of control centre tasks and an increasing amount of information to be
      processed. A method for establishing adequate levels of cognitive task load for
      the operators in such complex environments has been developed. It is based on a
      model distinguishing three load factors: time occupied, task-set switching, and
      level of information processing. Application of the method resulted in eight
      scenarios for eight extremes of task load (i.e. low and high values for each load
      factor). These scenarios were performed by 13 teams in a high-fidelity control
      centre simulator of the Royal Netherlands Navy. The results show that the method
      provides good prediction of the task load that will actually appear in the
      simulator. The model allowed identification of under- and overload situations
      showing negative effects on operator performance corresponding to controlled
      experiments in a less realistic task environment. Tools proposed to keep the
      operator at an optimum task load are (adaptive) task allocation and interface
      support.

PMID- 17008256
TI  - Automated assistance for human factors analysis in complex systems.
AB  - A tool and a method for scenario-based workload assessment and performance
      validation in complex socio-technical systems design, such as command and control
      rooms of military vessels, are described. We assess workload in terms of
      communication and the task load that each agent is able to handle. The method
      employs subjective task and communication estimates used to calculate the
      workload of human operators, using static and scenario-based analyses. This
      enables the identification of bottlenecks to be addressed by the designer with
      the appropriate allocation of function between humans and smart technology. This
      task is supported by the functional allocation adviser tool. A case study
      demonstrating the use of the tool for the design of the command and control room
      of a military vessel is presented.

PMID- 17008257
TI  - Distributed situation awareness in dynamic systems: theoretical development and
      application of an ergonomics methodology.
AB  - The purpose of this paper is to propose foundations for a theory of situation
      awareness based on the analysis of interactions between agents (i.e. both human
      and non-human) in subsystems. This approach may help to promote a better
      understanding of technology-mediated interaction in systems, as well as helping
      in the formulation of hypotheses and predictions concerning distributed situation
      awareness. It is proposed that agents within a system each hold their own
      situation awareness, which may be very different from (although compatible with)
      that of other agents. It is argued that we should not always hope for, or indeed
      want, sharing of this awareness, as different system agents have different
      purposes. This view marks situation awareness as a dynamic and collaborative
      process binding agents together on tasks on a moment-by-moment basis.
      Implications of this viewpoint for the development of a new theory of, and
      accompanying methodology for, distributed situation awareness are offered.

PMID- 17008258
TI  - Measuring team situation awareness in decentralized command and control
      environments.
AB  - Decentralized command and control settings like those found in the military are
      rife with complexity and change. These settings typically involve dozens, if not
      hundreds to thousands, of heterogeneous players coordinating in a distributed
      fashion in a dynamically networked battlefield laden with sensor data,
      intelligence reports, communications, and plans emanating from many different
      perspectives. Consider the concept of team situation awareness in this setting.
      What does it mean for a team to be aware of a situation or, more importantly, of
      a critical change in a situation? Is it sufficient or necessary for all
      individuals on the team to be independently aware? Or is there some more holistic
      awareness that emerges as team members interact? We re-examine the concept of
      team situation awareness in decentralized systems beyond an individual-oriented
      knowledge-based construct by considering it as a team interaction-based
      phenomenon. A theoretical framework for a process-based measure called
      'coordinated awareness of situations by teams' is outlined.

PMID- 17008259
TI  - A framework for managing system disturbances and insights from air traffic
      management.
AB  - System disturbances are likely to be a key factor affecting the acceptance and
      safety of future automation. Since hardware and software are rarely totally
      reliable, humans are always required in socio-technical command and control
      environments such as air traffic management (ATM). Unfortunately, human
      automation interaction is known to be problematic, particularly when the human
      assumes a monitoring or back-up role. Hence an understanding of how humans manage
      system disturbances is required, together with a method of looking at the problem
      for new systems. In this paper we outline a contextual framework of the process
      by which people recover from system disturbances, together with literature data
      and findings from 31 interviews with ATM personnel. The framework describes the
      context and causes of a problem, the problem itself, the effect and exposure, the
      recovery process, and the outcome. The framework, together with the research
      findings and operational experience, is also the basis for a performance
      prediction tool called the Recovery from Automation Failure Tool (RAFT).

PMID- 17008260
TI  - Event Analysis of Systemic Teamwork (EAST): a novel integration of ergonomics
      methods to analyse C4i activity.
AB  - C4i is defined as the management infrastructure needed for the execution of a
      common goal supported by multiple agents in multiple locations and technology. In
      order to extract data from complex and diverse C4i scenarios a descriptive
      methodology called Event Analysis for Systemic Teamwork (EAST) has been
      developed. With over 90 existing ergonomics methodologies already available, the
      approach taken was to integrate a hierarchical task analysis, a coordination
      demand analysis, a communications usage diagram, a social network analysis, and
      the critical decision method. The outputs of these methods provide two summary
      representations in the form of an enhanced operation sequence diagram and a
      propositional network. These offer multiple overlapping perspectives on key
      descriptive constructs including who the agents are in a scenario, when tasks
      occur, where agents are located, how agents collaborate and communicate, what
      information is used, and what knowledge is shared. The application of these
      methods to live data drawn from the UK rail industry demonstrates how alternative
      scenarios can be compared on key metrics, how multiple perspectives on the same
      data can be taken, and what further detailed insights can be extracted. The
      ultimate aim of EAST is, by applying it across a number of scenarios in different
      civil and military domains, to provide data to develop generic models of C4i
      activity and to improve the design of systems aimed at enhancing this management
      infrastructure.

PMID- 17008261
TI  - A naturalistic study of railway controllers.
AB  - There is an increasing prevalence for work to be analysed through naturalistic
      study, especially using ethnographically derived methods of enquiry and
      qualitative field research. The relatively unexplored domain of railway control
      (in comparison to signalling) in the UK is described in terms of features derived
      from observations and semi-structured interviews. In addition, task diagrams (a
      technique taken from the Applied Cognitive Task Analysis toolkit) are used to
      represent controllers' core elements of work, i.e. to manage events or incidents,
      and to identify the challenging steps in the process. The work features
      identified, the task diagrams, and the steps identified as challenging form a
      basis from which future ergonomics studies on railway controllers in the UK will
      be carried out.

PMID- 17008262
TI  - Human processes of control: tracing the goals and strategies of control room
      teams.
AB  - This study utilized a process tracing methodology to analyse the goals and
      strategies of control room teams in dealing with an unpredicted plant
      disturbance. The human processes of control used by operators and their
      supervisors, and interactions between them, were analysed during phases of
      detection, diagnosis, and control of a small plant leak. Five control room teams
      were videotaped tackling this simulated scenario on a full-scale simulator. The
      results found substantial differences both within and between teams in how the
      goals of monitoring and implementing procedures during the detection phase, and
      problem-solving and plant control during the diagnosis phase were achieved. The
      temporal patterning of the activities associated with these goals revealed that
      the teams used different strategies. The training implications of these findings
      are discussed, in particular with respect to the control room supervisor who had
      a pivotal role.

PMID- 17008263
TI  - Supporting command and control training functions in the emergency management
      domain using cognitive systems engineering.
AB  - The design and implementation of MERMAIDS, a computer-based training system in
      the domain of emergency command and control, is described. The research
      investigates the use of cognitive systems engineering and information management
      tools for modelling and representing training knowledge of emergency system
      operators. We propose a decision-centric human-computer interface as a new method
      of supporting computer-based modelling in the domain of emergency systems.
      Several interacting themes in information management relevant to emergency
      response planning are discussed.

PMID- 17008264
TI  - The hypogonadal (hpg) mouse as a model to investigate the estrogenic regulation
      of spermatogenesis.
AB  - The hypogonadal (hpg) mouse is an excellent animal model in which to investigate
      the mechanism of action of estrogens on spermatogenesis because it has arrested
      reproductive development without the need for surgical, endocrine,
      pharmacological or immunological intervention. Hpg mice are hypogonadotrophic and
      fail to show normal postnatal testicular development due to the congenital
      inability to synthesize gonadotropin-releasing hormone in the hypothalamus. The
      hpg testis remains responsive to gonadotropins and androgens in that fertility
      can be induced by treatment with these hormones. Surprisingly, chronic treatment
      with low concentrations of estradiol alone induces qualitatively normal
      spermatogenesis. The induction of testicular development by estradiol in hpg mice
      is accompanied by a paradoxical increase in FSH production. The actions of
      estradiol in hpg mice appear to be via genomic estrogen receptors, as concurrent
      treatment with estrogen-receptor antagonist ICI182,780 completely blocks these
      pituitary and testis responses. Concurrent treatment with the androgen receptor
      antagonist bicalutamide does not affect the estradiol-induced increase in
      pituitary FSH content, but markedly attenuates the estradiol-induced increase in
      testicular weight. Western blot analyses and immunohistochemistry provide
      evidence for estrogen-receptor alpha and beta expression in both pituitary gland
      and testis of the hpg mouse. Estradiol may therefore exert direct actions within
      the testes and/or indirect neuroendocrine actions via the release of FSH or other
      hormones from the pituitary gland, but its actions are dependent upon the
      availability of low levels of androgen within the testis.

PMID- 17008265
TI  - Gamete/embryo - oviduct interactions: implications on in vitro culture.
AB  - Fertilization and development of mouse embryos occur in the oviduct. Accumulating
      data suggested that embryo-maternal communication exists in the preimplantation
      period, with the female reproductive tract providing the optimal microenvironment
      conducive to the development of embryos. Signals produced from the developing
      embryos not only affect their own transport in the oviduct, but the physiology
      and gene expression patterns of the oviduct. As a step towards understanding the
      action of embryos on oviductal physiology, both genomics and proteomics
      approaches are being used to unveil the underlying mechanism of embryo-maternal
      interaction at the preimplantation stage. Results from recent studies allow us to
      better understand the roles and the use of oviductal secretory proteins or
      factors that affect embryo development in vivo and in vitro. It has been shown
      that in vitro culture alters gene expression of the cultured embryos and may
      predispose the embryo to certain disease. Therefore, the interaction between
      gamete/embryo and oviduct in vitro and in vivo, and the long-term effects of
      embryo culture on foetal development warrant further investigation.

PMID- 17008266
TI  - Analysing the performance of in vitro fertilization clinics in the United
      Kingdom.
AB  - During the past century, the manufacturing industry has achieved major successes
      in improving the quality of its products. An essential factor in these successes
      has been the use of Walter A. Shewhart's pioneering work in the economic control
      of variation, which culminated in the development of a simple yet powerful theory
      of variation, which classifies variation as having a common or special cause and
      thus guides the user to the most appropriate action to effect improvement. Using
      publicly available performance data, which includes percentage of live births and
      multiple births, for in vitro fertilization (IVF) clinics in the United Kingdom,
      we show a central role for Shewhart's approach in moving away from the
      limitations and controversies associated with performance league tables towards
      data analyses to support continual improvement. We outline strategies for dealing
      with common and special causes of variation in IVF clinic performance data.

PMID- 17008267
TI  - A pelvic pseudoaneurysm (a rare complication of oocyte retrieval for IVF) treated
      by arterial embolization.
AB  - This is a case report of the diagnosis and treatment of a pelvic pseudoaneurysm
      in a patient. Her history leads to the conclusion that this developed following
      egg retrieval during in vitro fertilization six years earlier.

PMID- 17008268
TI  - Can 'abnormally' fertilized zygotes give rise to viable embryos?
AB  - Conventional practice in in vitro fertilization or intracytoplasmic sperm
      injection is to select the best quality embryos based on their morphology and
      cleavage status from a cohort of fertilized oocytes in which two pronuclei were
      observed at the time they were checked for fertilization. However, in a small
      proportion of cycles, the selection is limited to embryos that appeared to be
      either unfertilized (displaying zero pronuclei) or abnormally fertilized
      (displaying one or three pronuclei) at the time they were checked for
      fertilization. There is a lack of consensus on whether such embryos should be
      transferred to the uterus. Cytogenetic analysis of embryos from oocytes with one
      pronucleus has shown a proportion is diploid. Transfer of such embryos has
      resulted in healthy births. Limited cytogenetic analysis of oocytes that divide
      despite the absence of pronuclei at fertilization check indicates that a
      proportion also have a normal cytogenetic constitution. Cytogenetic analysis of
      embryos from oocytes with three pronuclei has shown high rates of triploidy and
      chaotic cell divisions. Subsequent foetuses have extremely unfavourable outcomes.
      Here, we review the published literature on the cytogenetic analysis of
      'unfertilized' and 'abnormally fertilized' embryos and discuss possible pathways
      which lead to their formation. The limited evidence indicates that oocytes with
      one pronucleus and oocytes that show normal onward division despite the absence
      of pronuclei may be considered for replacement in certain circumstances.

PMID- 17008269
TI  - Molar pregnancy, childhood cancer and genomic imprinting - is there a link?
AB  - The United Kingdom Childhood Cancer Study (UKCCS) is a national multi-centre case
      control study that was designed to evaluate the potential aetiological role of
      prenatal events in childhood cancer. The obstetric records of 2692 mothers of
      children diagnosed with cancer and 4864 mothers of children without cancer were
      available for analysis. Overall, 1754 (65%) case mothers and 3220 (66%) control
      mothers had at least one prior pregnancy before the birth of the index child. Of
      these, 12 (0.68%) of the former and 9 (0.28%) of the latter had a prior molar
      pregnancy (odds ratio 2.5, 95% confidence interval 1.1 - 6.1). Both childhood
      cancer and molar pregnancy are rare neoplastic events, and the numbers are small.
      Nonetheless, whilst the associations were strongest for common precursor B-cell
      acute lymphoblastic leukaemia (OR 5.2, 95% CI 1.9 - 14.7) and sarcoma (OR 6.2,
      95% CI 1.3 - 30.3), the spread across the remaining diagnostic groups suggests
      that the relationship, if confirmed, may be of a generalized, rather than
      specific, type. This is the first time that an association between childhood
      cancer and hydatidiform mole has been reported. The UKCCS's systematic use of
      clinical records permitted a more precise characterization of reproductive events
      than is possible in investigations that rely on individuals own accounts, and we
      are confident that our findings cannot be explained by recall bias or other
      methodological limitations. Accordingly, we suggest that there may be an
      aetiologic connection between molar pregnancy and childhood cancer, and speculate
      here on the various genetic/epigenetic mechanisms that could be involved.

PMID- 17008270
TI  - The optimal length of 'coasting protocol' in women at risk of ovarian
      hyperstimulation syndrome undergoing in vitro fertilization.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life
      threatening complication following ovarian stimulation for in vitro fertilization
      (IVF). Coasting is the practice whereby the gonadotrophins are withheld and the
      administration of human chorionic gonadotrophin (hCG) is delayed until serum
      oestradiol (E2) has decreased to what is considered to be a safe level, to
      prevent the onset of OHSS. This study aimed to assess the length of coasting on
      the reproductive outcome in women at risk of developing OHSS. Coasting was
      undertaken when the serum E2 concentrations were > or = 17000 pmol/L but < 21000
      pmol/L. Daily E2 measurements were performed and hCG was administered when
      hormone levels decreased to < 17000 pmol/L. Eighty-one women who had their
      stimulation cycles coasted were grouped according to the number of coasting days.
      Severe OHSS occurred in one case, which represented 1.2% of patients who
      underwent coasting because of an increased risk of developing the syndrome. No
      difference was found between cycles coasted for 1 - 3 days and cycles coasted for
      > or = 4 days in terms of oocyte maturity, fertilization and embryo cleavage
      rates. Women in whom coasting lasted for > or = 4 days had significantly fewer
      oocytes retrieved (P < 0.05) and decreased implantation rate (P < 0.05) compared
      to those coasted for 1 - 3 days. Pregnancy rate/embryo transfer and live birth
      rate did not differ between groups. In conclusion, coasting appears to decrease
      the risk of OHSS without compromising the IVF cycle pregnancy outcome. Prolonged
      coasting is, however, associated with reduced implantation rates, perhaps due to
      the deleterious effects on the endometrium rather than the oocytes.

PMID- 17008271
TI  - Implementation of the NICE guideline - recommendations from the British Fertility
      Society for national criteria for NHS funding of assisted conception.
AB  - Assisted conception providers in England were surveyed to establish the uptake of
      NICE guideline for infertility particularly in respect of assisted conception and
      the criteria used to accept patients for NHS funded treatment. Detailed
      information on selection criteria was obtained from a group of commissioning
      consortia at an advanced stage in their arrangements. While there was an overall
      increase in the number of NHS IVF cycles purchased in England, implementation is
      stalled at one fresh cycle in the vast majority of Primary Care Trusts (PCTs).
      There is little consensus about the criteria used for acceptance into an NHS
      programme. This is particularly so in respect of social criteria which are often
      arbitrary and used as a rationing tool. This information complements that
      provided by the survey of Primary Care Trusts performed in March 2005 by the All
      Party Parliamentary Group on Infertility (APPGI) in partnership with the National
      Infertility Awareness Campaign (NIAC) which together provide a basis for
      recommendations for NHS funding. The recommendations presented should be applied
      across England and Wales to ensure consistency, fairness and equity of access.

PMID- 17008275
TI  - Evaluation of oestrogen and progesterone receptor status in HER-2 positive breast
      carcinomas and correlation with outcome.
AB  - AIM: HER-2/neu amplification occurs in 15-25% of breast carcinomas. This
      oncogene, also referred to as c-erbB-2, encodes a transmembrane tyrosine kinase
      receptor belonging to the epidermal growth factor receptor family. HER-2 over
      expression is reported to be associated with a poor prognosis in breast carcinoma
      patients and in some studies is associated with a poorer response to anti
      oestrogen therapy. These patients are less likely to benefit from CMF
      (cyclophosphamide, methotrexate, fluorouracil)-based chemotherapy compared with
      anthracycline-based chemotherapy. The aim of this study was to evaluate breast
      carcinomas to determine hormone receptor status and if there is a difference in
      breast cancer specific survival for HER-2 positive patients. METHODS: A total of
      591 breast carcinomas were evaluated using immunohistochemistry (IHC) for
      oestrogen receptor (ERp), progesterone receptor (PRp) and three different HER-2
      antibodies (CB11, A0485 and TAB250). Percentage of tumour cells and intensity of
      staining for ERp were evaluated using a semiquantitative method. RESULTS: Of the
      591 tumours, 91 (15.4%) showed 3+ membrane staining for HER-2 with one or more
      antibodies. Of these 91 tumours, 41 (45.1%) were ERp+/PRp+, seven (7.7%) were
      ERp+/PR-, six (6.6%) were ERp-/PRp+ and 37 (40.7%) were ERp-/PR-. Of HER-2
      positive tumours, 5.5% showed >80% 3+ staining for ERp compared with 31.8% of 0
      2+ HER-2 tumours; 24.2% of HER-2-positive tumours showed 60% or more cells with
      2+ or 3+ staining for ERp. Treatment data were available for 209 patients and no
      difference was observed in breast cancer specific survival (BCSS) with HER-2
      status and tamoxifen. CONCLUSION: Oestrogen receptor status cannot be used to
      select tumours for evaluation of HER-2 status, and oestrogen and progesterone
      receptor positivity does not preclude a positive HER-2 status. There is a higher
      proportion of ERp negative tumours associated with HER-2 positivity, however,
      more than 20% of HER-2 positive tumours show moderate or strong staining for ERp.
      HER-2 positive patients in this study did not show an adverse BCSS with tamoxifen
      treatment unlike some previous studies.

PMID- 17008276
TI  - Aberrant FHIT protein expression in classical Hodgkin's lymphoma: a potential
      marker.
AB  - AIMS: The fragile histidine triad (FHIT) gene is frequently inactivated in human
      cancers; however, the FHIT gene remains unexplored in Hodgkin's lymphoma. The aim
      of this study was to investigate the role of FHIT expression in classical
      Hodgkin's lymphoma. METHODS: Classical Hodgkin's lymphomas were analysed for FHIT
      gene expression by two-step non-biotin immunohistochemical method and Western
      blotting. RESULTS: Thirty of the 33 (91%) cases of Hodgkin's lymphoma tested were
      positive for FHIT protein by immuohistochemistry. The expression of FHIT was
      mainly located in cytoplasm of Reed-Sternberg (HRS) cells. The protein expression
      was also documented by Western blotting. The non-Hodgkin's lymphomas were
      negative for FHIT protein. CONCLUSIONS: The results indicate that abnormal FHIT
      expression is noted frequently in classical Hodgkin's lymphoma and the expression
      can give insight into the pathogenesis of the disease. The protein may serve as a
      marker to localise HRS cells in classical Hodgkin's lymphoma.

PMID- 17008277
TI  - Expression of adhesion proteins E-cadherin, alpha-catenin, beta-catenin and gamma
      catenin is different in T1 and T2 breast tumours.
AB  - BACKGROUND: Breast cancer is the most common malignancy in women. Although an
      increasing number of patients with breast cancer are being cured by surgery, a
      considerable number of patients suffer relapse in the form of metastases after
      surgery. E-cadherin and catenins have documented roles in breast cancer
      progression. Mammography is supposed to decrease breast cancer mortality by
      detecting tumours while they are small and before they have reached a clinically
      detectable stage. AIM: In the present study, we wanted to evaluate whether there
      are differences in expression patterns of adhesion proteins, shown to be crucial
      in the metastatic process, between small tumours detected by mammography and
      clinically detected large tumours. METHODS: Expression of E-cadherin, alpha
      catenin, beta-catenin and gamma-catenin was analysed using immunohistochemistry
      methods in 86 invasive breast carcinomas detected by mammography and compared
      with 90 clinically palpable invasive breast carcinomas. RESULTS: In the group of
      tumours detected by mammography (86 samples), reduced expression of E-cadherin
      was observed in 12 (14%) samples. Reduced expression of alpha-catenin was
      observed in four (4.6%) samples, and three (3.5%) samples showed reduced
      expression of beta-catenin. All samples showed strong expression of gamma
      catenin. When expression patterns of these proteins were evaluated in 90
      clinically detected tumours, we observed reduced expression of E-cadherin in 58
      (64.4%) samples, 12 (13.3%) samples showed reduced expression of alpha-catenin,
      while nine (10%) samples showed reduced expression of beta-catenin. Strong
      expression of gamma-catenin was detected in all tumours also in this
      group.Statistical analyses revealed a highly significant difference in expression
      of E-cadherin (p<0.001). However, no statistically significant differences were
      observed in expression of alpha-catenin (p = 0.081) and beta-catenin (p = 0.092)
      between the two groups of tumours. CONCLUSION: Results indicate that T1 breast
      tumours harbour less alterations in E-cadherin-catenin complexes and therefore
      are probably less likely to disseminate, and patients probably have a better
      prognosis than if tumours are diagnosed as T2.

PMID- 17008278
TI  - The prognostic significance of angiogenesis and the effect of vascular
      endothelial growth factor on angiogenic process in Wilms' tumour.
AB  - AIMS: There is a subgroup of patients with Wilms' tumour (WT) having favourable
      clinicopathological features but adverse outcome. We aimed to investigate the
      prognostic significance of angiogenesis and whether it can be used for predicting
      which patients will fall into this category, and the possible role of vascular
      endothelial growth factor (VEGF) on angiogenesis in WT. METHODS: Tumours in
      nephrectomy specimens from 63 WT patients were investigated for
      neovascularisation and VEGF expression by immunohistochemistry. The endothelial
      cells were highlighted by anti-CD34 and anti-CD31, and the microvessels in the
      hot-spots were counted. Correlations between the microvessel density (MVD), VEGF
      expression, clinicopathological features and prognosis were studied. RESULTS:
      Among 21 patients with follow-up data, favourable histology was detected in 17,
      seven of which died of disease. Patients with highly vascular tumours showed
      significantly poorer prognosis than those with low vascular tumours. There was no
      significant relationship between angiogenesis and VEGF expression. VEGF
      immunostaining revealed various patterns in different components of WT.
      CONCLUSIONS: We suggest that high MVD can be used as an indicator of poor
      prognosis with WT patients displaying favourable histology and there might be
      some additional growth factors other than VEGF which may also be responsible for
      angiogenesis in WTs.

PMID- 17008279
TI  - Perivascular epithelioid cell tumour (PEComa) of the soft tissue.
AB  - AIMS: PEComa is a rare tumour developing from perivascular epithelioid cells
      (PEC) and is characterised by positive immunoreactivity for HMB45. Since PEComas
      are tumours having both a spindle cell component and an epithelioid and giant
      cell component, as seen in many sarcomas, as well as having a wide distribution
      in various organs and soft tissue, we reviewed cases originally diagnosed as
      sarcomas of the soft tissue in our institution and screened them by
      immunostaining for HMB45. METHODS: Consecutive soft tissue sarcomas (31 tumours)
      retrieved from the Surgical Pathology file at our institution for a period of 3
      years were submitted for immunostaining for HMB45. Cases with positive HMB45
      immunostaining were submitted for further immunostaining for MART1, CD68, S100
      protein, cytokeratin AE1/3, EMA, vimentin, MSA and CD117. RESULTS: Of 31
      sarcomas, three tumours in the group of 11 malignant fibrous histiocytomas (MFH)
      and unclassified sarcomas showed positive immunoreactivity for HMB45 and MART1 in
      1-25% of tumour cells. The three tumours were located in the lower extremities
      and measured 8, 11 and 12 cm in diameter. Patient gender male:female was 2:1 and
      ages were 46, 56 and 60 years. Microscopically, the tumours were composed of a
      variable proportion of spindled cells, multinucleated cells and epithelioid cells
      disposed in diffuse sheets or nests. Mitotic figures and necrosis were frequent.
      The immunoreactivity was diffuse for CD68, focal for AE3 and EMA, negative or
      focal for MSA and CD117, and negative for S100 and AE1. All three patients
      developed lymph node or distant metastases and died of the disease within 1-2
      years. CONCLUSIONS: PEComa re-screened from the group of high grade sarcomas
      without definite differentiation range from pleomorphic to monomorphic
      cytohistopathological features. Immunostaining for HMB45 of unclassified sarcomas
      is useful for the classification of these tumours. They occur preferentially in
      the lower extremities and have a high malignant potential when associated with
      large size, tumoural necrosis and high mitotic activity.

PMID- 17008280
TI  - Inverse relationships between the expression of MMP-7 and MMP-11 and predictors
      of poor prognosis of papillary thyroid carcinoma.
AB  - AIMS: Matrix metalloproteinases (MMPs) have various functions that play roles in
      carcinoma development. In this study, we investigated the expression of two
      representative MMPs, MMP-7 and MMP-11, in papillary thyroid carcinomas. METHODS:
      We immunohistochemically investigated the expression of these MMPs in 196 cases
      of papillary carcinoma. RESULTS: A high level of MMP-7 expression was observed in
      56 cases (28.3%). The expression level was significantly decreased in cases
      showing large tumour, N positivity, large pT and poor differentiation. MMP-11
      expression was high in 119 cases (60.1%). The expression level was inversely
      related to tumour size, N factor, pT factor, pN factor, extrathyroid extension,
      and poor differentiation. CONCLUSIONS: In contrast to other MMPs, MMP-7 and MMP
      11 are inversely linked to aggressive characteristics of papillary thyroid
      carcinoma and their down-regulations may even be a marker of poor prognosis in
      patients.

PMID- 17008281
TI  - Abundant expression of AMACR in many distinct tumour types.
AB  - AIMS: Alpha-methylacyl-CoA racemase (AMACR), a mitochondrial and peroxisomal
      enzyme, is a valuable tool to confirm the diagnosis of prostate cancer,
      especially if combined with basal cell markers. To extend this diagnostic utility
      to other neoplasias, we comprehensively surveyed AMACR expression in human
      tumours. METHODS: We performed immunohistochemical analyses on tissue microarrays
      of AMACR expression in over 125 different human tumour types and 80 normal
      tissues. RESULTS: Microarray analysis revealed that tumours with prominent AMACR
      expression included adenocarcinomas of the prostate (72%), hepatocellular
      carcinomas (77%), papillary renal cell carcinomas (70%), and colorectal
      adenocarcinomas (71%). AMACR expression was equally frequent in colorectal
      adenomas and carcinomas. No significant difference in AMACR expression between
      untreated and hormone-refractory prostate cancers was observed. In the thyroid,
      AMACR expression was found in 42% of the follicular carcinomas but in only 16% of
      follicular adenomas. However, a more detailed analysis on a thyroid tissue
      microarray did not confirm a significant difference of AMACR expression in
      follicular adenoma and carcinomas. CONCLUSION: Taken together, the results
      indicate that AMACR is expressed in a wide variety of adenocarcinomas, and its
      diagnostic utility is restricted to specific areas.

PMID- 17008282
TI  - Heterogeneous proliferation of type II pneumocytes in usual interstitial
      pneumonia.
AB  - AIMS: Heterogeneous alveolar fibrosis, the most specific pathological finding in
      idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), enables
      differentiation of UIP from other interstitial pneumonias. Heterogeneous and mild
      alveolar injury may occur, and this will be a clue to clarifying the pathogenesis
      of UIP. METHODS: We examined nine lung biopsy specimens obtained from patients
      with IPF and five control specimens. We semi-quantitatively examined alveolar
      injury by measuring the density of type II pneumocytes. Serial 3 microm sections
      were stained with anti-Thomsen-Friedenreich (TF) antibody. We divided each UIP
      lesion into three areas: area near fibrosis (fibrous area), area with an
      apparently normal alveolar structure (normal area), and area between the fibrous
      and normal areas (intervening area). RESULTS: Immunostaining with anti-TF
      antibody stained the apical surface of type II pneumocytes and enabled us to
      recognise and count type II pneumocytes. The density of type II pneumocytes was
      increased in the fibrous area, and gradually decreased away from the fibrous
      lesion. The densities of type II pneumocytes in the above three areas were,
      respectively: 13.9+/-2.0, 7.2+/-1.6, and 9.5+/-1.6/mm alveolar length. The
      densities in the fibrous and intervening areas were significantly greater than
      those in the normal area and in control specimens (6.6+/-0.7/mm). CONCLUSIONS: If
      the density of type II pneumocytes indicates their degree of regeneration after
      alveolar injury, it reflects the severity of the pre-existing injury. This study
      confirms that heterogeneous and mild alveolar injury occurs in UIP.

PMID- 17008283
TI  - Characterisation and confirmation of rare beta-thalassaemia mutations in the
      Malay, Chinese and Indian ethnic groups in Malaysia.
AB  - AIMS: In Malaysia, about 4.5% of the Malay and Chinese populations are
      heterozygous carriers of beta-thalassaemia. The initial identification of rare
      beta-globin gene mutations by genomic sequencing will allow the development of
      simpler and cost-effective PCR-based techniques to complement the existing
      amplification refractory mutation system (ARMS) and gap-PCR used for the
      identification of beta-thalassaemia mutations. METHODS: DNA from 173 beta
      thalassaemia carriers and five beta-thalassaemia major patients from the Malay,
      Chinese and Indian ethnic groups were first analysed by ARMS and gap-PCR. Ninety
      five per cent (174/183) of the 183 beta-globin genes studied were characterised
      using these two techiques. The remaining nine uncharacterised beta-globin genes
      (4.9%) were analysed using genomic sequencing of a 904 bp amplified PCR product
      consisting of the promoter region, exon 1, intervening sequence (IVS) 1, exon 2
      and the 5' IVS2 regions of the beta-globin gene. RESULTS: The rare beta-globin
      mutations detected in the Chinese patients were CD27/28 (+C) and CD43 (GAG-TAG),
      and -88 (C-T) in an Indian patient. Beta-globin mutations at CD16 (-C), IVS1-1 (G
      A), IVS2-1 (G-A), -86 (C-G) and Haemoglobin South Florida (CD1, GTG-ATG) were
      confirmed in the Malay patients. CONCLUSIONS: The seven rare beta-globin
      mutations and a rare haemoglobin variant confirmed in this study have been
      described in other populations but have not been previously described in
      Malaysian beta-thalassemia patients.

PMID- 17008284
TI  - Prevalence of factor V R2 (H1299R) polymorphism in the Lebanese population.
AB  - AIMS: A recently identified polymorphism in factor V gene (His1299Arg; also named
      HR2) has been reported to be a possible risk factor for the development of venous
      thromboembolism (VTE), with a high prevalence of 9.5-15.2% in patients of
      different ethnic groups in different parts of the world. The aim of this study is
      to assess the prevalence of HR2 haplotype in Lebanon. METHODS: We randomly
      selected 125 samples from unrelated donors logged into our HLA registry; these
      represent healthy Lebanese individuals originating from different provinces and
      religious communities of the country. Their DNA was extracted using the Pel-Freez
      extraction kit and stored at -80 degrees C for later use. The CVD StripAssay was
      used for PCR and reverse hybridisation. It screens for several gene mutations
      including factor V H1299R. RESULTS: A total of 125 controls were studied: 72
      males and 53 females with a median age 42 years. Thirteen (10.4%) had the HR2
      haplotype; 11 (8.8%) were heterozygous (R1/R2), and two (1.6%) were homozygous
      (R2/R2), with an allelic frequency of 0.06. CONCLUSIONS: Our study is the first
      report from Lebanon that describes the prevalence of HR2 haplotype and the
      frequency of its alleles. We are reporting a high prevalence of the HR2 in our
      population (10.4%). The hypothesis that A4070G polymorphism might contribute to
      the expression of a thrombotic phenotype deserves to be tested in our population
      through larger studies.

PMID- 17008285
TI  - Evidence that the gonococcal porA pseudogene is present in a broad range of
      Neisseria gonorrhoeae strains; suitability as a diagnostic target.
AB  - AIMS: The primary aim of the study was to determine if the gonococcal porA
      pseudogene is a stable sequence target for the detection of Neisseria gonorrhoeae
      by PCR. METHODS: A total of 240 gonococcal strains from various geographic
      locations were tested by porA pseudogene PCR. In addition, porA pseudogene PCR
      positivity rates were compared with established gonococcal assays in three
      Australian states. RESULTS: All N. gonorrhoeae isolates provided positive results
      in the porA pseudogene PCR. Positivity rates compared favourably with established
      gonococcal assays, with increased N. gonorrhoeae detection in the Northern
      Territory and Western Australia. CONCLUSIONS: The results of this multicentre
      study provide further evidence that the porA pseudogene is highly conserved
      across a diverse range N. gonorrhoeae strains and is a suitable PCR target for
      routine detection of N. gonorrhoeae.

PMID- 17008286
TI  - Test and Teach. Mysterious waxy deposit in urine. Urine contamination with
      paracetamol suppository which had not been recorded in the clinical notes.

PMID- 17008287
TI  - Extensive calcification within a gastrointestinal stromal tumour: a potential
      diagnostic pitfall.

PMID- 17008288
TI  - Islet of Langerhans heterotopia in Meckel's diverticulum.

PMID- 17008289
TI  - Symptomatic renal leiomyoma: report of two cases.

PMID- 17008290
TI  - Fine needle aspiration diagnosis of metastatic Merkel cell carcinoma with
      multinucleated bizarre tumour cells in a post-renal transplant patient.

PMID- 17008291
TI  - Primary hepatic carcinoid tumours: report of two cases.

PMID- 17008292
TI  - Struma ovarii in a patient with a history of papillary thyroid carcinoma.

PMID- 17008293
TI  - Chondromyxoid fibroma of the distal clavicle.

PMID- 17008294
TI  - A case of dermatopathic lymphadenitis diagnosed by fine needle aspiration.

PMID- 17008295
TI  - Tubule neck dysplasia: precursor lesion of signet ring cell carcinoma and the
      immunohistochemical profile.

PMID- 17008296
TI  - MICE: a potential histopathological pitfall.

PMID- 17008297
TI  - Fetal fibronectin assay may reduce management cost of preterm labour: an interval
      analysis.

PMID- 17008298
TI  - Maybe babies are different.

PMID- 17008299
TI  - Roxithromycin induced hypersensitivity pneumonitis.

PMID- 17008302
TI  - Thrombin activatable fibrinolysis inhibitor (TAFI)--how does thrombin regulate
      fibrinolysis?
AB  - The thrombin-catalysed conversion of plasma fibrinogen into fibrin and the
      development of an insoluble fibrin clot are the final steps of the coagulation
      cascade during haemostasis. A delicate balance between coagulation and
      fibrinolysis determines the stability of the fibrin clot. Thrombin plays a
      central role in this process, it not only forms the clot but it is also involved
      in stabilizing the clot by activating thrombin activatable fibrinolysis inhibitor
      (TAFI). Activated TAFI protects the fibrin clot against lysis. Here we will
      discuss the mechanisms for regulation of fibrinolysis by thrombin. The role of
      the coagulation system for the generation of thrombin and for the activation of
      TAFI implies that defects in thrombin generation will directly affect the
      protection of clots against lysis. Thus, defects in activation of TAFI might
      contribute to the severity of bleeding disorders. Vice versa an increased
      activation of TAFI due to an increased rate of thrombin generation might lead to
      thrombotic disorders. Specific inhibitors of activated TAFI or inhibitors that
      interfere with the generation of thrombin might provide novel therapeutic
      strategies for thrombolytic therapy. Besides having a role in the regulation of
      fibrinolysis, TAFI may also have an important function in the regulation of
      inflammation, wound healing and blood pressure.

PMID- 17008303
TI  - The metabolic syndrome: role of skeletal muscle metabolism.
AB  - Skeletal muscle constitutes the largest insulin-sensitive tissue in the body and
      is the primary site for insulin-stimulated glucose utilization. Skeletal muscle
      resistance to insulin is fundamental to the metabolic dysregulation associated
      with obesity and physical inactivity, and contributes to the development of the
      metabolic syndrome (MS). The inability to efficiently take up and store fuel, and
      to transition from fat to glucose as the primary source of fuel during times of
      caloric abundance (high insulin) or scarcity (low insulin) has been termed
      metabolic inflexibility which contributes to a whole body metabolic dysregulation
      and cardiovascular risk. Potential mechanisms contributing to reduced insulin
      signaling and action in skeletal muscle includes adipose tissue expansion and
      increased inflammatory adipokines, increased renin-angiotensin-aldosterone system
      (RAAS) activity, decreases in muscle mitochondrial oxidative capacity, increased
      intramuscular lipid accumulation, and increased reactive oxygen species. Future
      research is focused upon understanding these and other potential mechanisms in
      order to identify therapeutic targets for reducing MS risk. Strategies will
      include adequate physical activity and maintaining a healthy weight, but may also
      require specific pharmacologic interventions.

PMID- 17008304
TI  - Mutations of TGFbeta signaling molecules in human disease.
AB  - The transforming growth factor beta (TGFbeta) signaling pathway regulates several
      biological processes including cellular proliferation, differentiation,
      apoptosis, migration, and extracellular matrix deposition. Ligand and receptor
      family members signal through two main Smad signaling branches, TGFbeta/activin
      to Smad2/3 (Sma and MAD-related proteins) and bone morphogenetic protein (BMP) to
      Smad1/5. At the molecular level, TGFbeta acts by modifying cytoskeletal
      organization and ultimately regulating expression of specific target genes.
      Germline disruption of TGFbeta signaling leads to several types of hereditary
      congenital malformation or dysfunction of the skeletal, muscular and/or
      cardiovascular systems, and to cancer predisposition syndromes. In this review,
      the molecular etiology of TGFbeta-associated disorders is examined, together with
      a discussion of clinical overlap between syndromes and possible biological
      explanations underlying the variable penetrance and expressivity of clinical
      characteristics. Increasing our understanding of the molecular etiology
      underlying genotype-phenotype correlations will ultimately provide a molecular
      based approach that should result in better prognostic tools, smart therapeutics
      and individualized disease management, not only for these rare syndromes, but for
      more generalized disorders of the cardiovascular and musculoskeletal systems and
      cancer. The clinical consequence of TGFbeta signaling mutations appears to depend
      on environmental factors and on the basal levels of ongoing signaling
      transduction networks specific to each individual. In this respect, genetic
      background might be a central factor in determining disease outcome and treatment
      strategy for TGFbeta-associated diseases.

PMID- 17008305
TI  - Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits
      and risks of therapeutic strategies.
AB  - Patients who take non-steroidal anti-inflammatory drugs (NSAIDs) may develop
      serious gastrointestinal (GI) side effects in both the upper and lower GI tract.
      Those at risk should be considered for prevention with misoprostol, proton pump
      inhibitor (PPI) or COX-2 selective inhibitor (coxib) therapy. A coxib or an
      NSAID+PPI combination is considered to have comparable GI safety profiles, but
      evidence from direct comparison is limited. PPIs are effective in the prevention
      of upper GI events in endoscopy trials and in a few, small, outcome trials in
      patients at risk. Coxibs have been evaluated in endoscopic ulcer studies and
      clinical outcome trials, and shown to significantly reduce the risk of upper GI
      ulcer and complications. Moreover, unlike PPIs, coxibs significantly reduce
      toxicity in the lower GI tract compared with NSAIDs. Coxibs and possibly some
      NSAIDs also increase the risk of developing serious cardiovascular events, an
      effect which may depend on the drug, dose and duration of therapy. It is not
      known whether concomitant low-dose aspirin use, which occurs in more than 20% of
      patients, will reduce the incidence of cardiovascular events, although
      concomitant aspirin increases the risk of developing serious GI events in
      patients taking either an NSAID or a coxib. Such patients may require additional
      PPI co-therapy. Current prevention strategies with an NSAID+PPI, misoprostol or a
      coxib must be considered in the individual patient with GI and cardiovascular
      risk factors. A PPI+coxib is indicated in those at highest risk (e.g. previous
      ulcer bleeding). PPI therapy must be considered for the treatment and prevention
      of NSAID-induced dyspepsia.

PMID- 17008306
TI  - Cell surface F1Fo ATP synthase: a new paradigm?
AB  - The mitochondrial F1Fo adenosine triphosphate (ATP) synthase is one of the most
      thoroughly studied enzyme complexes known. Yet, a number of new observations
      suggesting that the enzyme is also located on the cell surface necessitate
      further investigation. While the mitochondrial synthase utilizes the proton
      gradient generated by oxidative phosphorylation to power ATP synthesis, the cell
      surface synthase has instead been implicated in numerous activities, including
      the mediation of intracellular pH, cellular response to antiangiogenic agents,
      and cholesterol homeostasis. Intriguingly, a common thread uniting these various
      models of cell surface ATP synthase functions is the apparently caveolar
      distribution of the enzyme. Recent studies concerning the cell surface ATP
      synthase manifest applications in the regulation of serum cholesterol levels,
      cellular proliferation and antitumor strategies. This review addresses the
      expression, interactions, functions, and consequences of inhibition of cell
      surface ATP synthase, an enzyme now displaying a shift in paradigm, as well as of
      location.

PMID- 17008307
TI  - The NPAS3 gene--emerging evidence for a role in psychiatric illness.
AB  - NPAS3 is a member of the basic helix-loop-helix PAS domain class of transcription
      factors expressed in the brain. Evidence from a human chromosomal rearrangement
      and a mouse knock-out strain suggest that it may play a part in the aetiology of
      psychiatric illness. In this review, we describe evolutionary constraints on the
      NPAS3 gene, relevant functional studies from a related gene and the behavioural
      and hippocampal neurogenesis deficit observed in the mutant mouse. In addition,
      we speculate on the physiological regulation of NPAS3 and whether NPAS3 gene
      variation contributes to psychiatric illness at the population level.

PMID- 17008308
TI  - The zinc finger protein Ynr046w is plurifunctional and a component of the eRF1
      methyltransferase in yeast.
AB  - Protein release factor eRF1 in Saccharomyces cerevisiae, in complex with eRF3 and
      GTP, is methylated on a functionally crucial Gln residue by the S
      adenosylmethionine-dependent methyltransferase Ydr140w. Here we show that eRF1
      methylation, in addition to these previously characterized components, requires a
      15-kDa zinc-binding protein, Ynr046w. Co-expression in Escherichia coli of
      Ynr046w and Ydr140w allows the latter to be recovered in soluble form rather than
      as inclusion bodies, and the two proteins co-purify on nickel-nitrilotriacetic
      acid chromatography when Ydr140w alone carries a His tag. The crystal structure
      of Ynr046w has been determined to 1.7 A resolution. It comprises a zinc-binding
      domain built from both the N- and C-terminal sequences and an inserted domain,
      absent from bacterial and archaeal orthologs of the protein, composed of three
      alpha-helices. The active methyltransferase is the heterodimer Ydr140w.Ynr046w,
      but when alone, both in solution and in crystals, Ynr046w appears to be a
      homodimer. The Ynr046w eRF1 methyltransferase subunit is shared by the tRNA
      methyltransferase Trm11p and probably by two other enzymes containing a Rossman
      fold.

PMID- 17008309
TI  - G protein-coupled receptor kinase and beta-arrestin-mediated desensitization of
      the angiotensin II type 1A receptor elucidated by diacylglycerol dynamics.
AB  - Receptor desensitization progressively limits responsiveness of cells to
      chronically applied stimuli. Desensitization in the continuous presence of
      agonist has been difficult to study with available assay methods. Here, we used a
      fluorescence resonance energy transfer-based live cell assay for the second
      messenger diacylglycerol to measure desensitization of a model seven
      transmembrane receptor, the Gq-coupled angiotensin II type 1(A) receptor,
      expressed in human embryonic kidney 293 cells. In response to angiotensin II, we
      observed a transient diacylglycerol response reflecting activation and complete
      desensitization of the receptor within 2-5 min. By utilizing a variety of
      approaches including graded tetracycline-inducible receptor expression, mutated
      receptors, and overexpression or short interfering RNA-mediated silencing of
      putative components of the cellular desensitization machinery, we conclude that
      the rate and extent of receptor desensitization are critically determined by the
      following: receptor concentration in the plasma membrane; the presence of
      phosphorylation sites on the carboxyl terminus of the receptor; kinase activity
      of G protein-coupled receptor kinase 2, but not of G protein-coupled receptor
      kinases 3, 5, or 6; and stoichiometric expression of beta-arrestin. The findings
      introduce the use of the biosensor diacylglycerol reporter as a powerful means
      for studying Gq-coupled receptor desensitization and document that, at the levels
      of receptor overexpression commonly used in such studies, the properties of the
      desensitization process are markedly perturbed and do not reflect normal cellular
      physiology.

PMID- 17008310
TI  - Size matters: Erythromelalgia mutation S241T in Nav1.7 alters channel gating.
AB  - The Nav1.7 sodium channel is preferentially expressed in most nociceptive dorsal
      root ganglion neurons and in sympathetic neurons. Inherited erythromelalgia (IEM,
      also known as erythermalgia), an autosomal dominant neuropathy characterized by
      burning pain in the extremities in response to mild warmth, has been linked to
      mutations in Nav1.7. Recently, a substitution of Ser-241 by threonine (S241T) in
      the domain I S4-S5 linker of Nav1.7 was identified in a family with IEM. To
      investigate the possible causative role of this mutation in the pathophysiology
      of IEM, we used whole-cell voltage-clamp analysis to study the effects of S241T
      on Nav1.7 gating in HEK293 cells. We found a hyperpolarizing shift of activation
      midpoint by 8.4 mV, an accelerated time to peak, slowing of deactivation, and an
      increase in the current in response to small, slow depolarizations. Additionally,
      S241T produced an enhancement of slow inactivation, shifting the midpoint by 
      12.3 mV. Because serine and threonine have similar biochemical properties, the
      S241T substitution suggested that the size of the side chain at this position
      affected channel gating. To test this hypothesis, we investigated the effect of
      S241A and S241L substitutions on the gating properties of Nav1.7. Although S241A
      did not alter the properties of the channel, S241L mimicked the effects of S241T.
      We conclude that the linker between S4 and S5 in domain I of Nav1.7 modulates
      gating of this channel, and that a larger side chain at position 241 interferes
      with its gating mechanisms.

PMID- 17008311
TI  - Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral
      infection and double-stranded RNA.
AB  - Viral infection induces the production of interleukin (IL)-1beta and IL-18 in
      macrophages through the activation of caspase-1, but the mechanism by which host
      cells sense viruses to induce caspase-1 activation is unknown. In this report, we
      have identified a signaling pathway leading to caspase-1 activation that is
      induced by double-stranded RNA (dsRNA) and viral infection that is mediated by
      Cryopyrin/Nalp3. Stimulation of macrophages with dsRNA, viral RNA, or its analog
      poly(I:C) induced the secretion of IL-1beta and IL-18 in a cryopyrin-dependent
      manner. Consistently, caspase-1 activation triggered by poly(I:C), dsRNA, and
      viral RNA was abrogated in macrophages lacking cryopyrin or the adaptor ASC
      (apoptosis-associated speck-like protein containing a caspase-activating and
      recruitment domain) but proceeded normally in macrophages deficient in Toll-like
      receptor 3 or 7. We have also shown that infection with Sendai and influenza
      viruses activates the cryopyrin inflammasome. Finally, cryopyrin was required for
      IL-1beta production in response to poly(I:C) in vivo. These results identify a
      mechanism mediated by cryopyrin and ASC that links dsRNA and viral infection to
      caspase-1 activation resulting in IL-1beta and IL-18 production.

PMID- 17008312
TI  - Mitochondrial matrix copper complex used in metallation of cytochrome oxidase and
      superoxide dismutase.
AB  - A mitochondrial matrix copper ligand (CuL) complex, conserved in mammalian cells,
      is the likely source of copper for assembly of cytochrome c oxidase (CcO) and
      superoxide dismutase 1 (Sod1) within the intermembrane space (IMS) in yeast.
      Targeting the copper-binding proteins human Sod1 and Crs5 to the mitochondrial
      matrix results in growth impairment on non-fermentable medium caused by decreased
      levels of CcO. This effect is reversed by copper supplementation. Matrix-targeted
      Crs5 diminished Sod1 protein within the IMS and impaired activity of an inner
      membrane tethered human Sod1. Copper binding by the matrix-targeted proteins
      attenuates levels of the CuL complex without affecting total mitochondrial
      copper. These data suggest that attenuation of the matrix CuL complex via
      heterologous competitors limits available copper for metallation of CcO and Sod1
      within the IMS. The ligand also exists in the cytoplasm in an apparent metal-free
      state.

PMID- 17008313
TI  - The cytoplasmic substrate permeation pathway of serotonin transporter.
AB  - Serotonin transporter (SERT) catalyzes reuptake of the neurotransmitter serotonin
      (5-HT) and is a target for antidepressant drugs and psychostimulants. It is a
      member of a large family of neurotransmitter and amino acid transporters. A
      recent study using site-directed cysteine modification identified a helical
      region of the transporter with high accessibility to the cytoplasm. Subsequently,
      the high resolution structure of LeuT, a prokaryotic homologue, showed that the
      residues corresponding to this helical region are part of the fifth transmembrane
      domain. The accessibility of these positions is now shown to depend on
      conformational changes corresponding to interconversion of SERT between two forms
      that face the extracellular medium and the cytoplasm, respectively. Binding of
      the extracellular inhibitor cocaine decreased accessibility at these positions,
      whereas 5-HT, the transported substrate, increased it. The effect of 5-HT
      required the simultaneous presence of Na+ and Cl-, which are transported into the
      cell together (symported) with 5-HT. In light of the LeuT structure, these
      results begin to define the pathway through which 5-HT diffuses between its
      binding site and the cytoplasm. They also confirm a prediction of the alternating
      access model for transport, namely, that all symported substrates must bind
      together before translocation.

PMID- 17008314
TI  - Myeloid leukemia factor 1 associates with a novel heterogeneous nuclear
      ribonucleoprotein U-like molecule.
AB  - Myeloid leukemia factor 1 (MLF1) is an oncoprotein associated with hemopoietic
      lineage commitment and acute myeloid leukemia. Here we show that Mlf1 associated
      with a novel binding partner, Mlf1-associated nuclear protein (Manp), a new
      heterogeneous nuclear ribonucleoprotein (hnRNP) family member, related to hnRNP
      U. Manp localized exclusively in the nucleus and could redirect Mlf1 from the
      cytoplasm into the nucleus. The nuclear content of Mlf1 was also regulated by 14
      3-3 binding to a canonical 14-3-3 binding motif within the N terminus of Mlf1.
      Significantly Mlf1 contains a functional nuclear export signal and localized
      primarily to the nuclei of hemopoietic cells. Mlf1 was capable of binding DNA,
      and microarray analysis revealed that it affected the expression of several
      genes, including transcription factors. In summary, this study reveals that Mlf1
      translocates between nucleus and cytoplasm, associates with a novel hnRNP, and
      influences gene expression.

PMID- 17008315
TI  - Activation of STAT3 by G alpha(s) distinctively requires protein kinase A, JNK,
      and phosphatidylinositol 3-kinase.
AB  - Signal transducer and activator of transcription 3 (STAT3) can be stimulated by
      several G(s)-coupled receptors, but the precise mechanism of action has not yet
      been elucidated. We therefore examined the ability of Galpha(s)Q226L
      (Galpha(s)QL), a constitutively active mutant of Galpha(s), to stimulate STAT3
      Tyr705 and Ser727 phosphorylations in human embryonic kidney 293 cells. Apart
      from Galpha(s)QL, the stimulation of Galpha(s) by cholera toxin or beta2
      adrenergic receptor and the activation of adenylyl cyclase by forskolin, (Sp)
      cAMP, or dibutyryl-cAMP all promoted both STAT3 Tyr705 and Ser727
      phosphorylations. Moreover, the removal of Galpha(s) by RNA interference
      significantly reduced the beta2-adrenergic receptor-mediated STAT3
      phosphorylations, denoting its capacity to regulate STAT3 activation by a G
      protein-coupled receptor. The possible downstream signaling molecules involved
      were assessed by using specific inhibitors and dominant negative mutants.
      Induction of STAT3 Tyr705 and Ser727 phosphorylations by Galpha(s)QL was
      suppressed by inhibition of protein kinase A, Janus kinase 2/3, Rac1, c-Jun N
      terminal kinase (JNK), or phosphatidylinositol 3-kinase, and a similar profile
      was observed in response to beta2-adrenergic receptor stimulation. In contrast to
      the Galpha16-mediated regulation of STAT3 in HEK 293 cells (Lo, R. K., Cheung,
      H., and Wong, Y. H. (2003) J. Biol. Chem. 278, 52154-52165), the Galpha(s)
      mediated responses, including STAT3-driven luciferase activation, were resistant
      to inhibition of phospholipase Cbeta. Surprisingly, Galpha(s)-mediated
      phosphorylation at Tyr705, but not at Ser727, was resistant to inhibition of c
      Src, Raf-1, and MEK1/2 as well as to the expression of dominant negative Ras.
      Therefore, as with other Galpha-mediated activations of STAT3, the stimulatory
      signal arising from Galpha(s) is transduced via multiple signaling pathways.
      However, unlike the mechanisms employed by Galpha(i) and Galpha(14/16), Galpha(s)
      distinctively requires protein kinase A, JNK, and phosphatidylinositol 3-kinase
      for STAT3 activation.

PMID- 17008316
TI  - Similar transition states mediate the Q-cycle and superoxide production by the
      cytochrome bc1 complex.
AB  - The cytochrome bc complexes found in mitochondria, chloroplasts and many bacteria
      play critical roles in their respective electron transport chains. The quinol
      oxidase (Q(o)) site in this complex oxidizes a hydroquinone (quinol), reducing
      two one-electron carriers, a low potential cytochrome b heme and the "Rieske"
      iron-sulfur cluster. The overall electron transfer reactions are coupled to
      transmembrane translocation of protons via a "Q-cycle" mechanism, which generates
      proton motive force for ATP synthesis. Since semiquinone intermediates of quinol
      oxidation are generally highly reactive, one of the key questions in this field
      is: how does the Q(o) site oxidize quinol without the production of deleterious
      side reactions including superoxide production? We attempt to test three possible
      general models to account for this behavior: 1) The Q(o) site semiquinone (or
      quinol-imidazolate complex) is unstable and thus occurs at a very low steady
      state concentration, limiting O(2) reduction; 2) the Q(o) site semiquinone is
      highly stabilized making it unreactive toward oxygen; and 3) the Q(o) site
      catalyzes a quantum mechanically coupled two-electron/two-proton transfer without
      a semiquinone intermediate. Enthalpies of activation were found to be almost
      identical between the uninhibited Q-cycle and superoxide production in the
      presence of antimycin A in wild type. This behavior was also preserved in a
      series of mutants with altered driving forces for quinol oxidation. Overall, the
      data support models where the rate-limiting step for both Q-cycle and superoxide
      production is essentially identical, consistent with model 1 but requiring
      modifications to models 2 and 3.

PMID- 17008317
TI  - Human T-cell leukemia virus type I p30 nuclear/nucleolar retention is mediated
      through interactions with RNA and a constituent of the 60 S ribosomal subunit.
AB  - Human T-cell leukemia virus type I is the etiological agent of adult T-cell
      leukemia/lymphoma, an aggressive and fatal lymphoproliferative malignancy. The
      virus has evolved strategies to escape immune clearance by remaining latent in
      most infected cells in vivo. We demonstrated previously that virally encoded p30
      protein is a potent post-transcriptional inhibitor of virus replication (Nicot,
      C., Dundr, M., Johnson, J. M., Fullen, J. R., Alonzo, N., Fukumoto, R., Princler,
      G. L., Derse, D., Misteli, T., and Franchini, G. (2004) Nat. Med. 10, 197-201).
      p30 is unable to shuttle out of the nucleus in heterokaryon assays, suggesting
      the existence of specific retention signals. Because suppression of virus
      replication relies on nuclear retention of the tax/rex mRNA by p30, determining
      the retention features of p30 will offer hints to break latency in infected cells
      and insights into new therapeutic approaches. In this study, we used live cell
      imaging technologies to study the kinetics of p30 and to delineate its retention
      signals and their function in virus replication. Notably, this is the first study
      to identify p30 nucleolar retention domains. Using mutants of p30 that localized
      in different cellular compartments, we show that post-transcriptional control of
      virus replication by p30 occurs in the nucleoplasm. We further demonstrate that
      p30 nuclear/nucleolar retention is dependent upon de novo RNA transcripts and
      interactions with components of the ribosomal machinery.

PMID- 17008318
TI  - A derivative of lipid A is involved in signal recognition particle/SecYEG
      dependent and -independent membrane integrations.
AB  - A cell-free system was developed that allows the correct integration of single
      and multispanning membrane proteins of Escherichia coli into proteoliposomes. We
      found that physiological levels of diacylglycerol were required to prevent
      spontaneous integration into liposomes even of the polytopic mannitol permease.
      Using diacylglycerol-containing proteoliposomes, we identified a novel
      integration-stimulating factor. Integration of mannitol permease was dependent on
      both the SecYEG translocon and this factor and was mediated by signal recognition
      particle and signal recognition particle receptor. Integration of M13 procoat,
      which is independent of both signal recognition particle/signal recognition
      particle receptor and SecYEG, was also promoted by this factor. Furthermore, the
      factor stimulated the post-translational translocation of presecretory proteins,
      suggesting that it also mediates integration of a signal sequence. This factor
      was found to be a lipid A-derived membrane component possessing a peptide moiety.

PMID- 17008319
TI  - Differences in hydration coupled to specific and nonspecific competitive binding
      and to specific DNA Binding of the restriction endonuclease BamHI.
AB  - Using the osmotic stress technique together with a self-cleavage assay we measure
      directly differences in sequestered water between specific and nonspecific DNA
      BamHI complexes as well as the numbers of water molecules released coupled to
      specific complex formation. The difference between specific and nonspecific
      binding free energy of the BamHI scales linearly with solute osmolal
      concentration for seven neutral solutes used to set water activity. The observed
      osmotic dependence indicates that the nonspecific DNA-BamHI complex sequesters
      some 120-150 more water molecules than the specific complex. The weak sensitivity
      of the difference in number of waters to the solute identity suggests that these
      waters are sterically inaccessible to solutes. This result is in close agreement
      with differences in the structures determined by x-ray crystallography. We
      demonstrate additionally that when the same solutes that were used in competition
      experiments are used to probe changes accompanying the binding of free BamHI to
      its specific DNA sequence, the measured number of water molecules released in the
      binding process is strikingly solute-dependent (with up to 10-fold difference
      between solutes). This result is expected for reactions resulting in a large
      change in a surface exposed area.

PMID- 17008320
TI  - Removal of pattern-breaking sequences in microtubule binding repeats produces
      instantaneous tau aggregation and toxicity.
AB  - Aggregated and highly phosphorylated tau protein is a pathological hallmark of
      Alzheimer's disease (AD) and other tauopathies. We identified motifs of
      alternating polar and apolar amino acids within the microtubule-binding repeats
      of tau which were interrupted by small breaking stretches. Minimal mutation of
      these breaking sequences yielded a unique instantly aggregating tau mutant
      containing longer stretches of polar/apolar amino acids without losing its
      microtubule-binding capacity. These modifications produced rapid aggregation and
      cytotoxicity with accompanying occurrence of pathologic tau phosphoepitopes (AT8,
      AT180, AT270, AT100, Ser(422), and PHF-1) and conformational epitopes (MC-1 and
      Alz50) in cells. Similar to pathological tau in the pretangle state, toxicity
      appeared to occur early without the requirement for extensive fibril formation.
      Thus, our mutant protein provides a novel platform for the investigation of the
      molecular mechanisms for toxicity and cellular behavior of pathologically
      aggregated tau proteins and the identification of its interaction partners.

PMID- 17008321
TI  - Control of the p53-p21CIP1 Axis by E2f1, E2f2, and E2f3 is essential for G1/S
      progression and cellular transformation.
AB  - The E2F family of transcription factors is believed to have an essential role in
      the control of cellular proliferation by regulating the transcription of genes
      involved in cell cycle progression. Previous work has demonstrated that the
      targeted inactivation of E2f1, E2f2, and E2f3 results in elevated p21(CIP1)
      protein levels, loss of E2F target gene expression, and cell cycle arrest at G1/S
      and G2/M, suggesting a strict requirement for these E2Fs in the control of normal
      cellular proliferation. We now demonstrate that E2f1, E2f2, and E2f3 are also
      required for oncogene-mediated transformation of mouse embryonic fibroblasts.
      Analysis of synchronized populations of mouse embryonic fibroblasts revealed that
      the inactivation of p21(CIP1) restores the ability of E2f1-3-deficient cells to
      enter and transit through G1/S (but not G2/M). In contrast, loss of p53 restored
      the ability of these cells to progress through both G1/S and mitosis, leading to
      their continued proliferation. The inactivation of p53 (but not p21(CIP1))
      rendered E2f1-3-deficient cells sensitive to transformation and tumorigenesis.
      These results suggest that the negative regulation of the p53-p21(CIP1) axis by
      the E2F1-3 factors is critical for cell cycle progression and cellular
      transformation.

PMID- 17008322
TI  - Transgenic expression of group V, but not group X, secreted phospholipase A2 in
      mice leads to neonatal lethality because of lung dysfunction.
AB  - In an effort to elucidate the functions of secreted phospholipase A2 (sPLA2)
      enzymes in vivo, we generated transgenic (Tg) mice for group V sPLA2 (sPLA2-V)
      and group X sPLA2 (sPLA2-X), which act potently on phosphatidylcholine in vitro.
      We found that sPLA2-V Tg mice died in the neonatal period because of respiratory
      failure. The lungs of sPLA2-V Tg mice exhibited atelectasis with thickened
      alveolar walls and narrow air spaces, accompanied by infiltration of macrophages
      and only modest changes in eicosanoid levels. This severe pulmonary defect in
      sPLA2-V Tg mice was attributable to marked reduction of the lung surfactant
      phospholipids, phosphatidylcholine and phosphatidylglycerol. Given that the
      expression of sPLA2-V is greatly elevated in human lungs with severe
      inflammation, our present results raise the intriguing possibility that this
      isozyme may contribute to ongoing surfactant hydrolysis often observed in the
      lungs of patients with respiratory distress syndrome. In contrast, sPLA2-X Tg
      neonates displayed minimal abnormality of the respiratory tract with normal
      alveolar architecture and surfactant composition. This unexpected result was
      likely because sPLA2-X protein existed as an inactive zymogen in most tissues.
      The active form of sPLA2-X was detected in tissues with inflammatory granulation
      in sPLA2-X Tg mice. These results suggest that sPLA2-X mostly remains inactive
      under physiological conditions and that its proteolytic activation occurs during
      inflammation or other as yet unidentified circumstances in vivo.

PMID- 17008323
TI  - Ginsenoside-Rg1 induces vascular endothelial growth factor expression through the
      glucocorticoid receptor-related phosphatidylinositol 3-kinase/Akt and beta
      catenin/T-cell factor-dependent pathway in human endothelial cells.
AB  - Ginsenoside-Rg1, the most prevalent active constituent of ginseng, is a potent
      proangiogenic factor of vascular endothelial cells. This suggests that Rg1 may be
      a new modality for angiotherapy. Rg1 can activate the glucocorticoid receptor
      (GR). However, the regulatory steps downstream from GR that promote Rg1-induced
      angiogenesis have not been elucidated. Here we showed for the first time that Rg1
      was a potent stimulator of vascular endothelial growth factor (VEGF) expression
      in human umbilical vein endothelial cells, and importantly this induction was
      mediated through a phosphatidylinositol 3-kinase (PI3K)/Akt and beta-catenin/T
      cell factor-dependent pathway via the GR. Rg1 stimulation resulted in an increase
      in the level of beta-catenin, culminating its nuclear accumulation, and
      subsequent activation of VEGF expression. Transfection of a stable form of beta
      catenin (S37A) or the use of a glycogen synthase kinase 3beta inhibitor to
      stabilize beta-catenin induced VEGF synthesis, whereas small interfering RNA
      mediated down-regulation of beta-catenin did not, confirming that the effect was
      beta-catenin-specific. Using a luciferase reporter gene assay, we observed that
      Rg1 increased T-cell factor/lymphoid enhancer factor transcriptional activity.
      These events were mediated via a PI3K-dependent phosphorylation of the inhibitory
      Ser9 residue of glycogen synthase kinase 3beta. In addition, the GR antagonist
      RU486 was able to inhibit Rg1-induced PI3K/Akt and beta-catenin activation. These
      findings provide new insights into the mechanism responsible for Rg1 functions.

PMID- 17008324
TI  - Mitochondrial functions and estrogen receptor-dependent nuclear translocation of
      pleiotropic human prohibitin 2.
AB  - Proteins with multiple cellular functions provide biological diversity to
      eukaryotic cells. In the current studies, we identified the mitochondrial
      functions of human prohibitin 2 (PHB2), which was initially identified as a
      repressor of estrogen-dependent transcriptional activity. The mitochondrial
      complex of PHB2 consists of PHB1, voltage-dependent anion channel 2, adenine
      nucleotide translocator 2, and the anti-apoptotic Hax-1, which is a novel binding
      partner for PHB2. RNA interference-mediated knockdown of PHB2 in HeLa cells
      resulted in caspase-dependent apoptosis through down-regulation of Hax-1 and
      fragmentation of mitochondria. We also found that, although PHB2 is predominantly
      expressed in the mitochondria of HeLa cells, it translocates to nucleus in the
      presence of estrogen receptor alpha and estradiol. Here, we first demonstrated
      the roles of mammalian PHB2 in mitochondria and the molecular mechanism of its
      nuclear targeting and showed that PHB2 is a possible molecule directly coupling
      nuclear-mitochondrial interaction.

PMID- 17008325
TI  - Expression of molecules associated with tissue homeostasis in secretory
      endometria from untreated women with polycystic ovary syndrome.
AB  - BACKGROUND: The hormonal alterations observed in women with polycystic ovary
      syndrome (PCOS) may promote implantation failure as well as disruption of their
      endometrial homeostasis. To evaluate cell survival of mid-secretory endometrium
      from untreated women with PCOS, we measured the expression of apoptosis and
      proliferation-related proteins. METHODS: A case-control study of 11 patients with
      PCOS and 11 fertile women in the Hospital Research Unit was performed.
      Endometrial samples were obtained from PCOS women (PCOSE) and fertile healthy
      women (CE) during the mid-secretory phase of the menstrual cycle. Protein
      expressions for Akt, p-AktSer473 and p-AktThr308, Bad, p-BadSer136, Bcl-2, Bax
      and pro-caspase-3/caspase-3, were assessed by western blot, and Ki67 and p
      histone-3 (p-H3) by immunohistochemistry. RESULTS: In CE and PCOSE, a
      predominance of p-AktThr308 over p-AktSer473 is observed; p-BadSer136 expression
      is higher in PCOSE than in CE (P < 0.05). Also, Bcl-2 protein is overexpressed in
      PCOSE (P < 0.05), with no changes in Bax expression among the two groups,
      resulting in a significantly higher Bcl-2/Bax ratio in PCOSE than in CE (P <
      0.05). No changes in the expression of caspase-3 are obtained between both groups
      of endometria. Furthermore, cell proliferation detected by the expression of Ki67
      and p-H3 proteins is higher in the epithelia than the stroma of PCOSE versus CE
      (P < 0.05). CONCLUSION: The abnormal tissue homeostasis exhibited by the
      secretory endometrium from PCOS patients with spontaneous ovulation may interfere
      with their endometrial receptivity.

PMID- 17008326
TI  - Placental pathology of recurrent spontaneous abortion: the role of
      histopathological examination of products of conception in routine clinical
      practice: a mini review.
AB  - BACKGROUND: Histopathological examination of products of conception from
      miscarriages is part of routine clinical practice. The extent of additional
      clinically relevant information provided by this investigation in the setting of
      recurrent spontaneous abortion remains uncertain. METHODS: Review of the
      literature was performed to identify studies reporting on findings of
      histological examination of routinely obtained products of conception in the
      setting of recurrent spontaneous abortion. The initial search identified 312
      potential references, but 300 were excluded on further examination due to lack of
      data on specific histopathological findings in routine products of conception
      specimens from patients with recurrent spontaneous abortion. The 12 included
      studies indicated that such examination may identify hydatidiform moles, villous
      dysmorphic features suggesting fetal aneuploidy, chronic histiocytic
      intervillositis (CHI) and massive perivillous fibrin deposition and impaired
      trophoblast invasion. However, in most cases, morphological assessment cannot
      reliably determine the cause of the miscarriage or distinguish recurrent from
      sporadic miscarriage. Studies reporting on the use of additional
      immunohistochemical methods do not currently provide additional clinically useful
      diagnostic or prognostic information. CONCLUSION: Routine histological
      examination of products of conception in the setting of recurrent spontaneous
      abortion can provide important clinical information in a minority of cases.

PMID- 17008327
TI  - Cytokine and hormonal profile in blood serum and follicular fluids during ovarian
      stimulation with the multidose antagonist or the long agonist protocol.
AB  - BACKGROUND: The aim of our study was to explore cytokine and hormonal profiles in
      blood and follicular fluids from normal women stimulated with either the
      multidose antagonist or the long agonist protocol. METHODS: Fifty-six patients
      were stimulated with the multidose antagonist protocol and 12 with the long
      agonist protocol. Interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha
      (TNFalpha), leptin, vascular endothelial growth factor (VEGF), basic fibroblast
      growth factor (bFGF), estradiol (E(2)), progesterone and testosterone levels were
      measured in serum and follicular fluids by immunoassays. RESULTS: The two
      treatment groups had similar cytokine concentrations in serum. The
      intrafollicular concentrations of IL-1beta, IL-6, VEGF and leptin were also
      similar in the two groups. The concentrations of bFGF in follicular fluids from
      the antagonist group (169.5 +/- 113.2 ng/ml) were lower than those from the
      agonist group (249.7 +/- 119.8 ng/ml). bFGF concentrations were correlated with
      the amount of administered gonadotrophins (R = 0.364, P < 0.01) which was
      significantly lower in the antagonist group (antagonist group: 2037.7 +/- 725.8
      IU; agonist group: 2836.4 +/- 1163.5 IU). CONCLUSIONS: Normal women stimulated
      with either the multidose antagonist or the long agonist protocol generally have
      similar cytokine profiles in serum and follicular fluids. The intrafollicular
      levels of bFGF tend to be lower in antagonist cycles because of the lower amount
      of administered gonadotrophins.

PMID- 17008328
TI  - Type 2 diabetes and impaired fasting blood glucose in rural Bangladesh: a
      population-based study.
AB  - BACKGROUND: Diabetes is a fast expanding global health problem but more so in the
      developing countries. Therefore, it is of particular interest to study the
      epidemiological transition of the state and to identify the risk factors in order
      to recognize the extent of the problem. METHODS: A random sample of 5000 rural
      individuals (age >/=20 years) were included in a cross-sectional study. Fasting
      capillary blood glucose levels were measured from 4757 individuals. Height,
      weight, waist, hips including blood pressure and demographic information was
      collected. RESULTS: The study population was lean [mean body mass index (BMI)
      19.4] with a low prevalence of type 2 diabetes but relatively high impaired
      fasting glucose. No relationship between type 2 diabetes and BMI in men, but an
      overall relationship was observed for women (P = 0.04) (data not shown). Age,
      sex, and waist/hip ratio appeared to be important risk factors for the occurrence
      of type 2 diabetes in this population. CONCLUSIONS: Low prevalence of type 2
      diabetes and relative high impaired fasting blood glucose was observed. The
      factors associated with the occurrence of diabetes in this population appeared to
      differ than its known relations with BMI. This may indicate that the risk factors
      for type 2 diabetes are likely to differ in different population. Our results are
      likely to be in line with the Indian data suggesting that a revised guideline for
      anthropometric measures in the South Asian population is called for, in order to
      classify people at risk.

PMID- 17008329
TI  - The use of unipolar intracardiac impedance for discrimination of haemodynamically
      stable and unstable arrhythmias in man.
AB  - AIMS: To determine the feasibility of discriminating haemodynamically stable from
      unstable arrhythmias using right ventricular (RV) unipolar intracardiac impedance
      (Z). METHODS AND RESULTS: A quadrapolar temporary pacing electrode was positioned
      at the RV apex and unipolar impedance was measured between the tip electrode and
      a surface patch electrode. Changes in peak-to-peak Z amplitude were measured
      simultaneously with surface ECG and blood pressure during induced arrhythmias.
      Haemodynamic instability was defined as a systolic pressure of <90 mmHg. There
      were 25 episodes of ventricular fibrillation (VF) induced in 15 patients, 18
      episodes of ventricular tachycardia in 16 patients, and 33 episodes of
      supraventricular tachycardia (SVT) in 16 patients. Compared with the baseline
      rhythm, mean Z amplitude reduced from 51.3+/-7.7 to 11.2+/-7.4 Ohm (P<0.001)
      during VF, from 52.2+/-6.3 to 21.7+/-10.1 Ohm (P<0.01) during haemodynamically
      unstable VT, from 55.0+/-6.9 to 39.9+/-11 Ohm (ns) during stable VT, and from
      56.4+/-8.4 to 36.9+/-9.3 Ohm during SVT (P<0.001). CONCLUSION: Right ventricular
      unipolar impedance is an adequate sensor for determining mechanical ventricular
      contraction and acts as a surrogate marker for a fall in arterial blood pressure
      during VF. However, for ventricular and supraventricular tachycardias, variations
      between patients did not allow adequate discrimination between stable and
      unstable arrhythmias.

PMID- 17008330
TI  - Neural bases of personal and extrapersonal neglect in humans.
AB  - Human awareness of left space may be disrupted by cerebral lesions to the right
      hemisphere (hemispatial neglect). Current knowledge on the anatomical bases of
      this complex syndrome is based on the results of group studies that investigated
      primarily the best known aspect of the syndrome, which is visual neglect for near
      extrapersonal (or peripersonal) space. However, another component-neglect for
      personal space-is more often associated with, than double-dissociated from,
      extrapersonal neglect, especially, in chronic patients. The present investigation
      aimed at exploring the anatomical substrate of both extrapersonal and personal
      neglect by using different advanced methodological approaches to lesion-function
      correlation. Fifty-two right ischaemic patients were submitted to
      neuropsychological assessment and in-depth MRI evaluation. The borders of each
      patient's lesion were delimited onto its own high-resolution anatomical image and
      then submitted to an automated spatial normalization algorithm. Besides
      conventional lesion density plots and subtraction analysis, region-based
      statistical analyses were performed on percentage values of the lesioned tissue
      also using a new parcellation of the white matter (WM). Data were finally
      submitted to voxelwise statistical analysis using a recently proposed method
      (voxel-based lesion-symptom mapping). Results converged in showing that awareness
      of extrapersonal space is based on the integrity of a circuit of right frontal
      (ventral premotor cortex and middle frontal gyrus) and superior temporal regions,
      whereas awareness of personal space is rooted in right inferior parietal regions
      (supramarginal gyrus, post-central gyrus and especially the WM medial to them).
      Common but less crucial regions for both neglect sub-types were located in the
      temporo-peri-Sylvian cortex. We suggest that extrapersonal space awareness
      critically involves a ventral circuit recently described for the exogenous
      allocation and reorienting of attention in space. Disruption of personal space
      awareness, instead, seems to be due to a functional disconnection between regions
      important for coding proprioceptive and somatosensory inputs, and regions coding
      more abstract egocentric representations of the body in space. In conclusion,
      present data strongly support a segregation of personal and extrapersonal spatial
      awareness in humans, both from a functional and an anatomical point of view.

PMID- 17008331
TI  - A novel autosomal recessive limb-girdle muscular dystrophy with quadriceps
      atrophy maps to 11p13-p12.
AB  - Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of pathologies.
      We have identified a cohort of 14 French-Canadian patients from eight different
      families displaying a novel form of LGMD with an autosomal recessive inheritance.
      These patients share some features with previously described cases of 'quadriceps
      myopathy' that evolved into an LGMD. All demonstrate quadriceps femoris
      asymmetrical atrophy. Creatine kinase values were variable from normal to 6000
      U/l. Clinical evaluations and MRI studies demonstrate a variable intrafamilial
      and interfamilial phenotype. Asymmetrical muscle involvement was clinically
      observed and confirmed by imaging. MRI studies suggest that the hamstrings and
      the adductor magnus are the first limb muscles to demonstrate fatty infiltration.
      Muscle pathology shows no sign of active inflammation but increased endomysial
      connective tissue associated with basal lamina duplication and collagen
      disorganization. A genome-wide scan using the two largest families uncovered
      linkage to marker D11S1360 on chromosome 11p12 [multipoint logarithm of the odds
      (LOD) score of 2.78]. Further genotyping for the eight families confirmed linkage
      to this new LGMD locus (multipoint LOD score of 4.56). Fine mapping subsequently
      defined a less than 3.3 cM candidate interval on 11p13-p12. Haplotype analysis of
      carrier chromosomes suggests that the most frequent mutation may account for up
      to 81.3% of French-Canadian mutations. In this study, we describe the chromosomal
      locus of a new form of recessive LGMD with prominent quadriceps femoris atrophy.

PMID- 17008332
TI  - Spatial patterns of cortical thinning in mild cognitive impairment and
      Alzheimer's disease.
AB  - Cortical thickness is a more reliable measure of atrophy than volume due to the
      low variability in the cytoarchitectural structure of the grey matter. However,
      this more desirable measure of disease-related alterations is not fully evaluated
      in early dementia. The study presented here is the first to report the spatial
      patterns of cortical thickness in the pre-clinical stages of Alzheimer's disease,
      namely mild cognitive impairment (MCI). Cortical thickness measurements for 34
      healthy elderly, 62 MCI and 42 Alzheimer's disease subjects were made using fully
      automated magnetic resonance imaging-based analysis techniques in order to
      determine the pattern of cortical thinning as a function of disease progression.
      The thickness of the cortex decreased significantly when the healthy elderly
      brains were compared to those with MCI, mainly in the medial temporal lobe region
      and in some regions of the frontal and the parietal cortices. With the
      progression of disease from MCI to Alzheimer's disease, a general thinning of the
      entire cortex with significant extension into the lateral temporal lobe was
      found. In all cases, the results were more pronounced in the left hemisphere. In
      conclusion, we have shown that there is a specific pattern in the thinning of the
      cortical ribbon which is in agreement with the previous histological reports.
      These novel findings support the notion of increased isocortical involvement with
      the progression of disease.

PMID- 17008333
TI  - Perinatal risk factors altering regional brain structure in the preterm infant.
AB  - Neuroanatomical structure appears to be altered in preterm infants, but there has
      been little insight into the major perinatal risk factors associated with
      regional cerebral structural alterations. MR images were taken to quantitatively
      compare regional brain tissue volumes between term and preterm infants and to
      investigate associations between perinatal risk factors and regional
      neuroanatomical alterations in a large cohort of preterm infants. In a large
      prospective longitudinal cohort study of 202 preterm and 36 term infants, MR
      scans at term equivalent were undertaken for volumetric estimates of cortical and
      deep nuclear grey matter, unmyelinated and myelinated white matter (WM) and CSF
      within 8 parcellated regions for each hemisphere of the brain. Perinatal
      correlates analysed in relation to regional brain structure included gender,
      gestational age, intrauterine growth restriction, bronchopulmonary dysplasia,
      white matter injury (WMI) and intraventricular haemorrhage. Results revealed
      region-specific reductions in brain volumes in preterm infants compared with term
      controls in the parieto-occipital (preterm mean difference: -8.1%; 95% CI = -13.8
      -2.3%), sensorimotor (-11.6%; -18.2--5.0%), orbitofrontal (-30.6%; -49.8--11.3%)
      and premotor (-7.6%; -14.2--0.9%) regions. Within the sensorimotor and
      orbitofrontal regions cortical grey matter and unmyelinated WM were most clearly
      reduced in preterm infants, whereas deep nuclear grey matter was reduced mainly
      within the parieto-occipital and subgenual regions. CSF (ventricular and
      extracerebral) was doubled in volume within the superior regions in preterm
      infants compared with term controls. Cerebral WMI and intrauterine growth
      restriction were both associated with a more posterior reduction in brain
      volumes, whereas bronchopulmonary dysplasia was associated with a more global
      reduction across all regions. In contrast degree of immaturity was not related to
      regional brain structure among preterm infants. In summary, preterm birth is
      associated with regional cerebral tissue reductions, with the adverse pattern
      varying between risk factors. These findings add to our understanding of the
      potential pathways leading to altered brain structure and outcome in the preterm
      infant.

PMID- 17008334
TI  - Structural anatomy of empathy in neurodegenerative disease.
AB  - Empathy is a complex social behaviour mediated by a network of brain structures.
      Recently, several functional imaging studies have investigated the neural basis
      of empathy, but few corroborative human lesion studies exist. Severe empathy loss
      is a common feature of frontotemporal lobar degeneration (FTLD), and is also seen
      in other neurodegenerative diseases. In this study, the neuroanatomic basis of
      empathy was investigated in 123 patients with FTLD, Alzheimer's disease,
      corticobasal degeneration and progressive supranuclear palsy using the
      Interpersonal Reactivity Index (IRI). IRI Empathic Concern and Perspective taking
      scores were correlated with structural MRI brain volume using voxel-based
      morphometry. Voxels in the right temporal pole, the right fusiform gyrus, the
      right caudate and right subcallosal gyrus correlated significantly with total
      empathy score (P < 0.05 after whole-brain correction for multiple comparisons).
      Empathy score correlated positively with the volume of right temporal structures
      in semantic dementia, and with subcallosal gyrus volume in frontotemporal
      dementia. These findings are consistent with previous research suggesting that a
      primarily right frontotemporal network of brain regions is involved in emotion
      processing, and highlights the roles of the right temporal pole and inferior
      frontal/striatal regions in regulating complex social interactions. This is the
      first large-scale lesion study to investigate the neural basis of empathy using
      correlational analytic methods. The results suggest that the right anterior
      temporal and medial frontal regions are essential for real-life empathic
      behaviour.

PMID- 17008335
TI  - Seizure prediction: the long and winding road.
AB  - The sudden and apparently unpredictable nature of seizures is one of the most
      disabling aspects of the disease epilepsy. A method capable of predicting the
      occurrence of seizures from the electroencephalogram (EEG) of epilepsy patients
      would open new therapeutic possibilities. Since the 1970s investigations on the
      predictability of seizures have advanced from preliminary descriptions of seizure
      precursors to controlled studies applying prediction algorithms to continuous
      multi-day EEG recordings. While most of the studies published in the 1990s and
      around the turn of the millennium yielded rather promising results, more recent
      evaluations could not reproduce these optimistic findings, thus raising a debate
      about the validity and reliability of previous investigations. In this review, we
      will critically discuss the literature on seizure prediction and address some of
      the problems and pitfalls involved in the designing and testing of seizure
      prediction algorithms. We will give an account of the current state of this
      research field, point towards possible future developments and propose
      methodological guidelines for future studies on seizure prediction.

PMID- 17008336
TI  - Community patient education and exercise for people with fibromyalgia: a parallel
      group randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effects of a community patient education -exercise
      programme, using a cognitive-behavioural approach, for people with fibromyalgia.
      DESIGN: A randomized, parallel group trial with assessments at 0, 4 and 8 months.
      SETTING: Community leisure centres. SUBJECTS: People with fibromyalgia (n=183)
      attending a rheumatology outpatient department at a large district general
      hospital. INTERVENTIONS: Participants were randomized to a patient education
      exercise group (n=97) or relaxation (attention control) group (n=86). MAIN
      MEASURES: The Fibromyalgia Impact Questionnaire (0-80; lower score means better
      health). Secondary outcomes included: the Arthritis Self-Efficacy Scale(pain and
      other symptoms subscales: 1 -10 scale; higher scores mean greater self-efficacy)
      and self-reported improvement. RESULTS: Fifty participants withdrew or were
      unable to attend and 133 completed and returned baseline questionnaires: patient
      education group (n=71); relaxation group (n=62); 120/133 participants were women.
      Average age was 48.53 (SD 10.89) years. Follow-up ranged between 73 and 82% of
      questionnaires returned. At four months, there was a difference in average
      changes in total Fibromyalgia Impact Questionnaire scores between the two groups:
      patient education group--3.38 (SD 9.35); relaxation group 0.3 (SD 8.85); P=0.02.
      Arthritis Self-Efficacy Scale scores were significantly higher in the patient
      education group: pain 0.59 (SD 1.45)compared to the relaxation group's--0.12 (SD
      1.22); P=0.003; other symptoms (patient education group 0.72 (SD 1.33);
      relaxation group 0.03 (SD 1.16); P=0.002). At eight months these differences were
      no longer apparent. Forty-seven per cent in the patient education group self
      reported improvement compared with 13% in the relaxation group (chi2=13.65;
      P=0.0001). CONCLUSION: Short-term improvements resulted from the education 
      exercise programme but were not sustained. Appropriate selection may improve
      efficacy.

PMID- 17008337
TI  - Improving the rehabilitative management of client sexual health concerns after
      neurological disability: evaluation of a staff sexuality training programme in
      New Zealand.
AB  - OBJECTIVE: To evaluate the effectiveness of a staff sexuality training programme
      as a means of improving the rehabilitative management of client sexual health
      concerns after neurological disability. DESIGN: A prospective controlled pre- and
      posttest evaluation design with six-month follow-up. SUBJECTS: Seventy-four
      multidisciplinary rehabilitation and disability staff who attended a two-day
      workshop, and a control group of 25 staff members who did not receive the
      training. SETTING: Two workshops were held at major rehabilitation centres in the
      North and South Islands of New Zealand respectively. MAIN MEASURES: The Sex
      Attitude Scale, as well as three purpose-designed measures including an objective
      knowledge test, a self-rating inventory of skills and clinical activity, and a
      single-item measure of the degree of staff comfort. RESULTS: Workshop
      participants showed significant increases in knowledge, skills and comfort
      comparing pre-to post-workshop scores. A number of these gains were maintained at
      the six-month follow-up. There was an associated increase in the level of
      reported staff activity in addressing patient/client sexual health concerns in
      the six months to follow-up, compared to a similar time period preceding the
      workshop. In contrast, the control group had similar pre-workshop scores to the
      workshop participants, but recorded no increase on the measures, or in their
      level of reported activity, at the six-month follow-up. CONCLUSIONS: The
      programme showed initial promise as an effective intervention in upgrading the
      capacity of staff working in rehabilitation and disability agencies to address
      the sexual health concerns of their patients/clients.

PMID- 17008338
TI  - Task-oriented progressive resistance strength training improves muscle strength
      and functional performance in individuals with stroke.
AB  - OBJECTIVE: To examine the effectiveness of task-oriented progressive resistance
      strength training on lower extremity strength and functional performance in
      chronic stroke subjects. DESIGN: Single-blind, randomized controlled trial.
      SETTING: Medical centre and district hospital. SUBJECTS: Forty-eight subjects at
      least one year post stroke. INTERVENTIONS: Participants randomly allocated to two
      groups, control (n-/24) and experimental (n-/24). Subjects in the control group
      did not receive any rehabilitation training. Subjects in the experimental group
      were put on a four-week task-oriented progressive resistance strength training.
      MAIN MEASURES: Lower extremity muscle strength, gait velocity, cadence, stride
      length, six-minute walk test, step test, and timed up and go test. RESULTS:
      Muscle strength significantly improved in the experimental group for strong side
      muscle groups (ranged from 23.9% to 36.5%) and paretic side muscle groups (ranged
      from 10.1% to 77.9%). In the control group muscle strength changes ranged from
      6.7% gain to 11.2% decline. The experimental group showed significant improvement
      in all selected measures of functional performance except for the step test. In
      the control group, the number of repetitions of the step test significantly
      decreased (-20.3%) with no change in other functional tests. There was a
      significant difference between groups for muscle strength and all functional
      measures. The strength gain was significantly associated with gain in the
      functional tests. CONCLUSIONS: The task-oriented progressive resistance strength
      training programme could improve lower extremity muscle strength in individuals
      with chronic stroke and could carry over into improvement in functional
      abilities.

PMID- 17008339
TI  - Can quality of movement be measured? Rasch analysis and inter-rater reliability
      of the Motor Evaluation Scale for Upper Extremity in Stroke Patients (MESUPES).
AB  - OBJECTIVE: Clinical scales evaluating arm function after stroke are weak at
      detecting quality of movement. Therefore a new scale, the Motor Evaluation Scale
      for Upper Extremity in Stroke Patients (MESUPES), was developed, comprising 22
      items pertaining to arm and hand performance. The scale was investigated for
      validity and unidimensionality using the Rasch measurement model, and for inter
      rater reliability. SETTING: Twelve hospitals and rehabilitation centres in
      Belgium, Germany and Switzerland. PATIENTS: There were 396 patients (average age
      63.38+/-12.89 years) in the Rasch study and 56 patients (average age 65.68+/
      12.75 years) in the reliability study. MAIN MEASURES: The scale was examined on
      its fit to the Rasch model, thereby evaluating the scale's unidimensionality and
      validity. Differential item functioning was performed to test the stability of
      item hierarchy on several variables. Inter-rater reliability was examined with
      kappa values, weighted percentage agreement and intraclass correlation
      coefficients (ICC). RESULTS: Based on Rasch analysis, five items were removed.
      The MESUPES was divided in two tests: the MESUPES-arm test (8 items) and MESUPES
      hand test (9 items). Both scales fitted the Rasch model. All items were stable
      among the subgroups of the sample. ICCs were 0.95 (95% confidence interval (CI)
      0.91 -0.97) and 0.97 (95% CI 0.95-0.98) for the total score on arm and hand test
      respectively. The scale was also reliable at item level (weighted kappa 0.62 
      0.79, weighted percentage agreement 85.71 -98.21). CONCLUSION: The MESUPES-arm
      and MESUPES-hand meet the statistical properties of reliability, validity and
      unidimensionality. Both tests provide a useful clinical and research tool to
      qualitatively evaluate arm and hand function during recovery after stroke.

PMID- 17008340
TI  - The Community Balance and Mobility Scale--a balance measure for individuals with
      traumatic brain injury.
AB  - OBJECTIVE: To provide evidence for the validity and reliability of a new outcome
      measure of balance, the Community Balance and Mobility Scale, developed for the
      ambulatory individual with traumatic brain injury. DESIGN: A validity and
      reliability study. SETTING: Acute care, in- and outpatient rehabilitation and day
      hospital settings. SUBJECTS: Two convenience samples (n=36, 32) of ambulatory
      patients with traumatic brain injury. MAIN MEASURES: The content and construct
      validity, test-retest, inter- and intra-rater reliability and internal
      consistency of the Community Balance and Mobility Scale. RESULTS: Content
      validity was demonstrated by the involvement of patients with traumatic brain
      injury (n=7) and clinicians (n=17) in the process of item generation and by
      physical therapists' ratings of item relevance. Further support is the
      correlation of the Community Balance and Mobility Scale scores with physical
      therapists' global balance ratings of the patient (r=0.62). Construct validity
      was supported by the ability of the measure to differentiate between patients
      along the continuum of care and also by comparisons with maximal walking velocity
      (r=0.64). Patients who scored greater than or less than 50 on the balance measure
      demonstrated significantly different Community Integration Questionnaire scores
      (P=0.004). The Community Balance and Mobility Scale demonstrated intraclass
      correlation coefficients (ICCs) of 0.977, 0.977, 0.975 and Cronbach's alpha of
      0.96 for intra-, inter-, test-retest reliability and internal consistency,
      respectively. CONCLUSION: The Community Balance and Mobility Scale is a valid and
      reliable outcome measure for the ambulatory individual with traumatic brain
      injury.

PMID- 17008341
TI  - Hand function in Charcot Marie Tooth: test retest reliability of some
      measurements.
AB  - OBJECTIVE: To evaluate the reliability of some measurements of hand function in
      people with Charcot Marie Tooth disease. DESIGN: Test retest study. SETTING:
      University, hospitals/clinics in northern Sweden. SUBJECTS: Twenty people with
      Charcot Marie Tooth disease. MAIN OUTCOME MEASURES: Measures of (1) dexterity;
      Box and Block Test and Nine-Hole Peg Test, (2) strength; Grippit instrument (grip
      and pinch), (3) tactile sensation; Shape Texture Identification Test. Statistics
      used: intraclass correlation (ICC 2.1), limits of agreement, coefficient of
      repeatability, coefficient of variation, and linear weighted kappa. RESULTS: The
      ICC for the Box and Block Test was very high (0.95). The limits of agreement,
      coefficient of repeatability (CR) (11.5 blocks/min) and coefficient of variation
      (CV) (8.4%) were acceptable. There was bias towards a better result on the second
      occasion. For the Nine-Hole Peg Test, the reliability was good if performance was
      within 2 min (ICC =0.99, CR = 4.3 s, CV = 3.9%). Grip strength proved to be
      reliable (ICC = 0.99, CR = 26.7 N, CV = 6.6%), while pinch strength was less
      reliable. The kappa value of the Shape Texture Identification Test was 0.87,
      which was considered very good although the test has limitations in terms of how
      well it can describe patients either performing very well or very poorly.
      CONCLUSIONS: The tested instruments can all be used to evaluate hand function in
      people with Charcot Marie Tooth. Certain factors, however, like limited time
      aspects for the Nine-Hole Peg Test and the number of trials used, should be taken
      into consideration. Pinch strength evaluation should be interpreted with caution.

PMID- 17008342
TI  - Psychometric properties of the Fear-Avoidance Beliefs Questionnaire in patients
      with neck pain.
AB  - OBJECTIVES: To translate the Fear-Avoidance Beliefs Questionnaire and investigate
      the validity and reliability of the Chinese version of the questionnaire in
      patients with neck pain. DESIGN: Observational cross-sectional and prospective
      study. SETTING: Physiotherapy outpatient departments. SUBJECTS: Four samples with
      476 consecutive adult patients with neck pain from four physiotherapy centres.
      METHODS: The original questionnaire was translated into Chinese by forward and
      backward translation and reviewed by a panel of experts. The subjects completed
      the Chinese version of the fear-avoidance questionnaire, Northwick Park Neck Pain
      Questionnaire, Medical Outcomes 36-Item Short-Form Health Survey and their pain
      intensity was measured using an 11-point pain numerical rating scale. They were
      observed and measured at the beginning of physiotherapy, at week 3 and at week 6
      after treatment began. RESULTS: The questionnaire had very good content validity
      and test-retest reliability with an intraclass correlation coefficient of 0.81
      and Cronbach's alpha coefficient of 0.90. Spearman's correlation coefficients
      between fear-avoidance and the neck pain questionnaire, the health survey
      (physical), health survey (mental) and pain scale were 0.56, 0.45, 0.36 and 0.34,
      respectively. The standard response mean and effect size at week 6 were 0.38 and
      0.32, respectively. Factor analysis yielded three factors which accounted for
      61.6% of the total variance of the questionnaire. CONCLUSION: The Fear-Avoidance
      Beliefs Questionnaire is a valid and reliable tool for patients with neck pain.
      It has been shown to demonstrate very good content validity, a high degree of
      test-retest reliability and internal consistency, good construct validity and
      medium responsiveness.

PMID- 17008343
TI  - The criterion-related validity of the Northwick Park Dependency Score as a
      generic nursing dependency instrument for different rehabilitation patient
      groups.
AB  - OBJECTIVE: To investigate the criterion or concurrent validity of the Northwick
      Park Dependency Score (NPDS) for determining nursing dependence in different
      rehabilitation groups, with the Barthel Index (BI) and the Care Dependency Scale
      (CDS). DESIGN: Cross-sectional study. SETTING: Centre for Rehabilitation of the
      University Medical Center Groningen, The Netherlands. SUBJECTS: Patients after
      stroke, spinal cord injury, multitrauma, head injury, amputation, rheumatoid
      arthritis, diabetes mellitus, lung diseases, tuberculosis and coronary artery
      disease. One hundred and fifty-four patients were included. MEASURES: The
      Northwick Park Dependency Score (NPDS), the Barthel Index (BI) and the Care
      Dependency Scale (CDS). RESULTS: The correlation (rho) between the NPDS and the
      BI for all groups was -0.87; R2=0.76 (n=154). Per patient group rho varied from 
      0.70 (R2=0.49) to -0.93 (R2=0.86). The overall correlation between the NPDS and
      CDS was larger than the criterion of rho=0.60 (r=-0.74; R2=0.55) but was <0.60 in
      the rheumatoid arthritis and tuberculosis group. The overall correlation between
      BI and CDS exceeded the criterion (r=0.75; R2=0.56). CONCLUSIONS: The NPDS is a
      generic nursing dependency instrument that can be used as a valid measure across
      various patient groups in rehabilitation.

PMID- 17008344
TI  - The big finger: the second to fourth digit ratio is a predictor of sporting
      ability in women.
AB  - BACKGROUND: The second to fourth finger length ratio (2d:4d) is thought to be
      related to diverse traits including cognitive ability, disease susceptibility,
      and sexuality. OBJECTIVE: To examine the relationship between 2d:4d and sports
      ability in women. METHODS: Hand radiographs from 607 women (mean age 54 years)
      were used to estimate 2d:4d. Ranking of sports ability was on a scale (1-5).
      RESULTS: The highest achieved level of participation in any sport was
      significantly negatively associated with 2d:4d (b = -4.93, p = 0.01) as was the
      relationship between 2d:4d and running level (b = -6.81, p = 0.034). Ability in
      other sports also showed a negative relationship albeit non-significant.
      CONCLUSIONS: These results suggest that a low 2d:4d ratio is related to increased
      female sports ability. It can be postulated that this ratio may predict potential
      sports ability. Understanding the mechanisms underpinning this relationship may
      give important insights into musculoskeletal fitness, health and disease.

PMID- 17008345
TI  - Factors influencing the parotid function in nasopharyngeal carcinoma treated with
      parotid-sparing radiotherapy.
AB  - BACKGROUND: To evaluate the factors influencing post-irradiation parotid gland
      function in nasopharyngeal cancer treated with parotid-sparing radiotherapy.
      METHODS: This study consisted of 45 patients with nasopharyngeal cancer treated
      with radiotherapy including 3D conformal radiotherapy, intensity-modulated
      radiotherapy and high-dose-rate brachytherapy. The mean follow-up time was 37.5
      months (range: 15-50 months). Objective parotid gland function was assessed by
      series sialoscintigraphy pre-irradiation and post-irradiation at 1, 6, 12 and 18
      months. Subjective salivary function was recorded by the LENT/SOMA system.
      Wilcoxon signed-rank test was used to compare the secretion ratio (SR) of parotid
      gland before and after treatment. Mann-Whitney rank-sum test was used to
      determine the factors influencing the post-irradiated SR. Chi-square test was
      used to compare the correlation between subjective grading of xerostomia and
      objective grading of parotid glands. RESULTS: There was a significant difference
      between the pre-irradiation and post-irradiation parotid gland's SR at 1 (0.30
      versus 0.01, P < 0.05) and 6 months (0.03 versus 0.08, P < 0.05). However, there
      was no significant difference compared with the pre-irradiation SR at 12 (0.30
      versus 0.20, P > 0.05) and 18 months (0.30 versus 0.18, P > 0.05). There was
      significant correlation between subjective and objective salivary function (P =
      0.024) at 12 months after radiotherapy. The factor that impacted the preservation
      of parotid function was mean dose to the parotid gland >38.0 Gy (P < 0.05).
      CONCLUSIONS: Our results demonstrated that parotid function could recover 1 year
      after treatment with parotid-sparing radiotherapy in patients with nasopharyngeal
      cancer. The most important factor that influenced parotid function was the mean
      dose to the parotid gland.

PMID- 17008346
TI  - What is the appropriate oxygen tension for in vitro culture?

PMID- 17008347
TI  - Interaction between methyl CpG-binding protein and ran GTPase during cell
      division in tobacco cultured cells.
AB  - BACKGROUND AND AIMS: Methyl CpG-binding proteins are considered to play critical
      roles in epigenetic control of gene expression by recognizing and interacting
      with 5-methylcytosine (m(5)C) in eukaryotes. However, among 13 corresponding
      genes in Arabidopsis thaliana, designated as featuring a methyl-binding domain
      (MBD), only four have so far been shown actually to bind to m(5)C. One example,
      AtMBD5, was selected here to screen for interacting proteins. METHODS: Yeast two
      hybrid assays were used for screening, and physical interaction was confirmed by
      pull-down and bimolecular fluorescence complementation (BiFC) assays. Cellular
      localization was analysed by fluorescence-tagged fusion proteins using tobacco
      (Nicotiana tabacum) cultured bright yellow 2 cells. KEY RESULTS: A gene finally
      identified was found to encode AtRAN3, a protein that belongs to the Ran GTPase
      family, which plays a critical role in nucleocytoplasmic transport and spindle
      bipolarization during cell division. AtMBD5 and AtRAN3 were clearly shown to
      interact in the nucleus by BiFC. On co-expression of AtMBD5-cyan fluorescence
      protein and yellow fluorescence protein-AtRAN3 in tobacco cells, both localized
      to the nucleus in the resting stage, migrating to the cytoplasm, primarily around
      chromatin, during mitosis, particularly at metaphase. CONCLUSIONS: These results
      suggest that AtMBD5 becomes localized to the vicinity of chromosomes with the aid
      of AtRAN3 during cell division, and may play an important role not only in
      maintenance of chromatin structures by binding to m(5)C, but also in progress
      through mitosis by detaching from m(5)C. The present findings also shed light on
      the physiological function of Ran GTPases, direct target proteins of which have
      not thus far been well defined, suggesting their key role in chromatin movements
      in plant cells.

PMID- 17008348
TI  - Genetic diversity and the reproductive system in related species of antirrhinum.
AB  - BACKGROUND AND AIMS: Seven related species of Antirrhinum (A. siculum, A. majus,
      A. latifolium, A. linkianum, A. litigiosum, A. cirrhigherum and A. tortuosum)
      were studied in order to compare levels of genetic variation and its partitioning
      in them, and to check relationships between genetic patterns and the reproductive
      system. METHODS: Eight hundred and fifty-one plants were screened for variability
      at 13 allozyme loci by means of horizontal starch gel electrophoresis. Parameters
      of genetic diversity and its partitioning, the inbreeding coefficient as well as
      an indirect estimate of gene flow based on the equation: Nm = (1 - G(ST))/4G(ST),
      were calculated. KEY RESULTS: Genetic variability in A. siculum was found to be
      the lowest known in the genus. Mean values of F(IT) and F(IS) were mostly
      positive and not significantly different from zero. Population differentiation
      (F(ST)) ranged between 6.1 in A. tortuosum and 17.6 in A. linkianum. The
      inbreeding coefficient within populations ranged between F(IS) = -0.5 in A.
      tortuosum and F(IS) = 1 in A. siculum. Estimates of gene flow ranged between Nm =
      15 in A. majus (considered as very high) to Nm = 0.42 in A. siculum (considered
      as low). CONCLUSIONS: Correlation was found between levels of diversity and
      differentiation on one hand, and the reproductive system of the studied taxa on
      the other. Striking differences among species in the inbreeding coefficient
      (F(IS)) show different reproductive systems, which mostly support previous
      reports. Strategies for the conservation of A. siculum are recommended, such as
      preservation of natural populations as well as ex situ preservation of seeds from
      different populations.

PMID- 17008349
TI  - Low genetic structure in an epiphytic Orchidaceae (Oncidium hookeri) in the
      Atlantic rainforest of South-eastern Brazil.
AB  - BACKGROUND AND AIMS: Oncidium hookeri is a neotropical species of epiphytic
      Orchidaceae found in the Brazilian Atlantic rainforest at the top of the
      Mantiqueira Range of mountains. The genetic variation of O. hookeri was studied
      to assess the distribution of genetic variability within and among six
      populations localized in Atlantic rainforest remnants. Gene flow among
      populations and the occurrence of recent bottlenecks were investigated in order
      to infer the degree of isolation of these populations. METHODS: Thirteen
      polymorphic loci were used for allozyme electrophoresis. The data were analysed
      by means of standard statistical approaches, to estimate gene diversity and the
      genetic structure of the populations. KEY RESULTS: The mean gene diversity and
      allelic richness were H(e) = 0.099 and A = 1.75, respectively. F-statistics
      revealed high heterozygote deficiencies in all populations (F(IS) = 0.43-0.82).
      Several rare alleles were found in all the populations, and three populations
      presented private alleles. Low genetic differentiation among O. hookeri
      populations was detected (F(ST) = 0.029); natural selection may be involved in
      PGM locus differentiation among populations. The genetic differentiation between
      paired populations was low, bearing no correlation with geographic distance
      (Mantel test: r = -0.34, P = 0.72). Only two populations showed signs of recent
      bottlenecks. CONCLUSIONS: The heterozygote deficiency found seems to be caused by
      pollinator behaviour; the low frequencies of several alleles of different loci
      can be maintained due to clonal propagation. Despite the stochastic nature of the
      wind-dispersal of seeds to long distances, this process may promote an effective
      gene flow among populations, thus avoiding genetic differentiation.

PMID- 17008350
TI  - Differential resistance among host and non-host species underlies the variable
      success of the hemi-parasitic plant Rhinanthus minor.
AB  - BACKGROUND AND AIMS: Rhinanthus minor is a root hemiparasitic plant that attacks
      a wide range of host species which are severely damaged by the parasite.
      Rhinanthus minor also attempts unsuccessfully to form connections to a range of
      non-hosts which in contrast are not damaged by the parasite; however, the
      underlying physiological basis of these differences is not fully understood.
      METHODS: Biomass of host-parasite combinations was studied, and histology,
      electron microscopy and FT-IR microspectroscopy were used to determine the
      cellular-level interactions between Rhinanthus haustoria (the parasite's
      connective structure) and the roots of a range of potential host species.
      RESULTS: Two distinct defence responses were observed in the non-host forbs
      Plantago lanceolata and Leucanthemum vulgare. Firstly, L. vulgare was able to
      encapsulate the parasite's invading structures preventing it from gaining access
      to the stele. This was supported by FT-IR microspectroscopy, used to monitor
      lignification in response to Rhinanthus haustoria. Secondly, host cell
      fragmentation was observed at the interface between the parasite and P.
      lanceolata. Growth data confirmed the non-host status of the two forbs whilst, in
      contrast, grasses and a legume which were good hosts showed no evidence of
      defence at the host/parasite interface. CONCLUSIONS: Variable resistance to
      Rhinanthus is shown for the first time to be controlled by cellular-level
      resistance to haustoria by either cell fragmentation or lignification at the
      host/parasite interface.

PMID- 17008351
TI  - Ecophysiology of seed dormancy in the Australian endemic species Acanthocarpus
      preissii (Dasypogonaceae).
AB  - BACKGROUND AND AIMS: Seedlings of Acanthocarpus preissii are needed for coastal
      sand dune restoration in Western Australia. However, seeds of this Western
      Australian endemic have proven to be very difficult to germinate. The aims of
      this study were to define a dormancy-breaking protocol, identify time of suitable
      conditions for dormancy-break in the field and classify the type of seed dormancy
      in this species. METHODS: Viability, water-uptake (imbibition) and seed and
      embryo characteristics were assessed for seeds collected in 2003 and in 2004 from
      two locations. The effects of GA(3), smoke-water, GA(3) + smoke-water and warm
      stratification were tested on seed dormancy-break. In a field study, soil
      temperature and the moisture content of soil and buried seeds were monitored for
      1 year. KEY RESULTS: Viability of fresh seeds was >90 %, and they had a fully
      developed, curved-linear embryo. Fresh seeds imbibed water readily, with mass
      increasing approx. 52 % in 4 d. Non-treated fresh seeds and those exposed to 1000
      ppm GA(3), 1 : 10 (v/v) smoke-water/water or 1000 ppm GA(3) + 1 : 10 (v/v) smoke
      water/water germinated <8 %. Fresh seeds germinated to >80 % when warm-stratified
      for at least 7 weeks at 18/33 degrees C and then moved to 7/18 degrees C, whereas
      seeds incubated continuously at 7/18 degrees C germinated to <20 %. CONCLUSIONS:
      Seeds of A. preisii have non-deep physiological dormancy that is released by a
      period of warm stratification. Autumn (March/April) is the most likely time for
      warm stratification of seeds of this species in the field. This is the first
      report of the requirement for warm stratification for dormancy release in seeds
      of an Australian species.

PMID- 17008352
TI  - Labellar micromorphology of Bifrenariinae Dressler (Orchidaceae).
AB  - BACKGROUND AND AIMS: The two closely related subtribes Bifrenariinae Dressler and
      Maxillariinae Benth. are easily distinguished on morphological grounds. Recently,
      however, molecular techniques have supported the inclusion of Bifrenariinae
      within a more broadly defined Maxillariinae. The present paper describes the
      diverse labellar micromorphology found amongst representatives of Bifrenariinae
      (Bifrenaria Lindl., Rudolfiella Hoehne, Teuscheria Garay and Xylobium Lindl.) and
      compares it with that found in Maxillaria Pabst & Dungs and Mormolyca Fenzl
      (Maxillariinae). METHODS: The labella of 35 specimens representing 22 species of
      Bifrenariinae were examined by means of light microscopy and scanning electron
      microscopy and their micromorphology compared with that of Maxillaria sensu
      stricto and Mormolyca spp. The labellar epidermis of representatives of
      Bifrenaria, Xylobium and Mormolyca was tested for protein, starch and lipids in
      order to ascertain whether this tissue is involved in the rewarding of
      pollinators. KEY RESULTS AND CONCLUSIONS: The labella of Bifrenaria spp. and
      Mormolyca spp. are densely pubescent but those of Xylobium, Teuscheria and
      Rudolfiella are generally papillose. However, whereas the trichomes of Bifrenaria
      and Mormolyca are unicellular, those found in the other three genera are
      multicellular. Hitherto, no unicellular trichomes have been described for
      Maxillaria, although the labella of a number of species secrete a viscid
      substance or bear moniliform, pseudopollen-producing hairs. Moniliform hairs and
      secretory material also occur in certain species of Xylobium and Teuscheria and
      these genera, together with Maxillaria, are thought to be pollinated by stingless
      bees (Meliponini). Differences in the labellar micromorphology of Bifrenaria and
      Mormolyca are perhaps related to Euglossine- and/ or bumble bee-mediated
      pollination and pseudocopulation, respectively. Although Xylobium and Teuscheria
      share a number of labellar features with Maxillaria sensu stricto, this does not
      necessarily reflect taxonomic relationships but may be indicative of convergence
      in response to similar pollinator pressures.

PMID- 17008353
TI  - Heterogeneity in spatial P-distribution and foraging capability by Zea mays:
      effects of patch size and barriers to restrict root proliferation within a patch.
AB  - BACKGROUND AND AIMS: Localized proliferation of roots in nutrient-enriched
      patches seems to be an adaptive response in many plants, but its function is
      still debatable. To understand the efficiency and limitation of foraging
      behaviour, the impact of patch size and the presence or absence of a barrier to
      root proliferation within phosphorus (P)-enriched patches was examined. METHODS:
      In pots filled with P-poor soil, six treatments of heterogeneous P supply were
      prepared: three patch sizes with or without a root barrier between patches. In
      addition, a homogeneous P supply treatment was also prepared. Irrespective of
      these treatments, each pot received the same total amount of P. Maize (Zea mays)
      was grown in each pot for 45 d in a greenhouse. KEY RESULTS: P content and
      biomass were greatest in plants grown in the largest patch due to successful root
      proliferation, and were higher in the presence of a root barrier. Interestingly,
      plants preferentially developed adventitious nodal roots projecting from the stem
      into the P-enriched soil, particularly in the largest patch with a root barrier.
      Removal of the barrier reduced the P-uptake capacity per unit root surface area
      or volume in P-enriched patches, revealing that the P-uptake capacity per root
      can be suppressed even in P-rich soil if other portions on the root axis
      encounter P-poor conditions. CONCLUSIONS: The results suggest that the efficiency
      of root morphological plasticity is largely determined by the size of the P
      enriched patch. Furthermore, the results imply a novel aspect of P-uptake
      physiology that roots in heterogeneous P cannot demonstrate their potential
      capacity, as would be observed in roots encountering P continuously; this effect
      is probably mediated by an internal root factor.

PMID- 17008354
TI  - Glutathione reductase in leaves of cowpea: cloning of two cDNAs, expression and
      enzymatic activity under progressive drought stress, desiccation and abscisic
      acid treatment.
AB  - BACKGROUND AND AIMS: Reactive oxygen species are frequently produced when plants
      are exposed to abiotic stresses. Among the detoxication systems, two enzymes,
      ascorbate peroxidase and glutathione reductase (GR) play key roles. GR has also a
      central role in keeping the reduced glutathione pool during stress thus allowing
      the adjustments on the cellular redox reactions. The aim of this work was to
      study the variations in cytosolic and dual-targeted GR gene expression in the
      leaves of cowpea plants submitted to progressive drought, rapid desiccation and
      application of exogenous abscisic acid (ABA). METHODS: Two cowpea (Vigna
      unguiculata) cultivars, one drought-resistant ('EPACE-1'), the other drought
      sensitive ('1183') were submitted to progressive drought stress by withholding
      irrigation. Cut-off leaves were air-dried or treated with exogenous ABA. Two GR
      cDNAs, one cytosolic, the other dual-targeted to chloroplasts and mitochondria
      were isolated by PCR and cloned in plasmid vectors. Reverse-transcription PCR was
      used to study the variations in GR gene expression. KEY RESULTS: Two new cDNAs
      encoding a putative dual-targeted and a cytosolic GR were cloned and sequenced
      from leaves of V. unguiculata. Drought stress induced an up-regulation of the
      expression of the cytosolic GR gene directly related to the intensity of the
      stress in both cultivars. The expression of dual-targeted GR was up-regulated by
      the drought treatment in the susceptible cultivar only. Under a fast desiccation,
      the '1183' cultivar responded later than the 'EPACE-1', although in 'EPACE-1' it
      was the cytosolic isoform which responded and in '1183' the dual-targeted one.
      Exogenous ABA enhanced significantly the activity and expression levels of GR in
      both cultivars after treatment for 24 h. CONCLUSIONS: These results demonstrate a
      noticeable activation in both cultivars of the antioxidant metabolism under a
      progressive water stress, which involves both GR genes in the case of the
      susceptible cultivar. Under a fast desiccation, the susceptible cultivar
      responded later than the resistant one, suggesting a weaker capacity of response
      versus the resistant one. Exogenous ABA probably acts on GR gene expression via a
      mediated signal transduction pathway.

PMID- 17008355
TI  - Globozoospermia revisited.
AB  - Globozoospermia is a rare (incidence <0.1%) but severe disorder in male
      infertility. Total globozoospermia is diagnosed by the presence of 100% round
      headed spermatozoa lacking an acrosome. It is still unclear whether patients
      whose ejaculate contains both normal and globozoospermic cells (partial
      globozoospermia) suffer from a variation of the same syndrome. Apart from the
      fact that affected males suffer from reduced fertility or even infertility, no
      other physical characteristics can be associated with the syndrome. ICSI is a
      treatment option for these patients, although low fertilization rates after ICSI
      show a reduced ability to activate the oocyte. In globozoospermic cells, the use
      of acrosome markers has demonstrated an absent or severely malformed acrosome.
      Chromatin compaction appears to be disturbed but is not consistently over- or
      undercondensed. In some cases, an increased number of cells with DNA
      fragmentation have been observed. The analysis of the cytogenetic composition
      revealed an increased aneuploidy rate in some cases. Nonetheless, no increased
      number of spontaneous abortions or congenital defects has been reported in
      pregnancies conceived after ICSI. The pathogenesis of globozoospermia most
      probably originates in spermiogenesis, more specifically in acrosome formation
      and sperm head elongation. In several knockout mouse models, a phenotype similar
      to that in humans was found. Together with the occurrence of affected siblings,
      these findings indicate a genetic origin, which makes globozoospermia a good
      candidate for genetic analysis. More research is needed to elucidate the
      pathogenesis of human globozoospermia to further understand globozoospermia as
      well as (abnormalities in) spermiogenesis and spermatogenesis in general.

PMID- 17008356
TI  - A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in
      centronuclear myopathy.
AB  - In eukaryotic cells, phosphoinositides are lipid second messengers important for
      many cellular processes and have been found dysregulated in several human
      diseases. X-linked myotubular (centronuclear) myopathy is a severe congenital
      myopathy caused by mutations in a phosphatidylinositol 3-phosphate (PtdIns3P)
      phosphatase called myotubularin, and mutations in dominant centronuclear myopathy
      (CNM) cases were identified in the dynamin 2 gene. The genes mutated in autosomal
      recessive cases of CNMs have not been found. We have identified a novel
      phosphoinositide phosphatase (hJUMPY) conserved through evolution, which
      dephosphorylates the same substrates as myotubularin, PtdIns3P and
      PtdIns(3,5)P(2), in vitro and ex vivo. We found, in sporadic cases of CNMs, two
      missense variants that affect the enzymatic function. One of these appeared de
      novo in a patient also carrying a de novo mutation in the dynamin 2 gene. The
      other missense (R336Q) found in another patient changes the catalytic arginine
      residue of the core phosphatase signature present in protein tyrosine/dual
      specificity phosphatases and in phosphoinositide phosphatases and drastically
      reduces the enzymatic activity both in vitro and in transfected cells. The
      inheritance of the phenotype with regard to this variant is still unclear and
      could be either recessive with an undetected second allele or digenic. We propose
      that impairment of hJUMPY function is implicated in some cases of autosomal CNM
      and that hJUMPY cooperates with myotubularin to regulate the level of
      phosphoinositides in skeletal muscle.

PMID- 17008357
TI  - Secretin receptor-deficient mice exhibit impaired synaptic plasticity and social
      behavior.
AB  - Secretin is a peptide hormone released from the duodenum to stimulate the
      secretion of digestive juice by the pancreas. Secretin also functions as a
      neuropeptide hormone in the brain, and exogenous administration has been reported
      to alleviate symptoms in some patients with autism. We have generated secretin
      receptor-deficient mice to explore the relationship between secretin signaling in
      the brain and behavioral phenotypes. Secretin receptor-deficient mice are overtly
      normal and fertile; however, synaptic plasticity in the hippocampus is impaired
      and there are slightly fewer dendritic spines in the CA1 hippocampal pyramidal
      cells. Furthermore, secretin receptor-deficient mice show abnormal social and
      cognitive behaviors. These findings suggest that the secretin receptor system has
      an important role in the central nervous system relating to social behavior.

PMID- 17008358
TI  - Kinesin-2 mediates physical and functional interactions between polycystin-2 and
      fibrocystin.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in
      PKD1, encoding polycystin-1 (PC1), or PKD2 (polycystin-2, PC2). Autosomal
      recessive PKD (ARPKD) is caused by mutations in PKHD1, encoding
      fibrocystin/polyductin (FPC). No molecular link between ADPKD and ARPKD has been
      determined. Here, we demonstrated, by yeast two-hybrid and biochemical assays,
      that KIF3B, a motor subunit of kinesin-2, associates with PC2 and FPC. Co
      immunoprecipitation experiments using Madin-Darby canine kidney (MDCK) and inner
      medullary collecting duct (IMCD) cells and human kidney revealed that PC2 and
      KIF3B, FPC and KIF3B and, furthermore, PC2 and FPC are endogenously in the same
      complex(es), though no direct association between the PC2 and FPC intracellular
      termini was detected. In vitro binding and Far Western blot experiments
      demonstrated that PC2 and FPC are in the same complex only if KIF3B is present,
      presumably by forming a PC2-KIF3B-FPC complex. This was supported by our
      observation that altering KIF3B level in IMCD cells by over-expression or siRNA
      significantly affected complexing between PC2 and FPC. Immunofluorescence
      experiments showed that PC2, FPC and KIF3B partially co-localized in primary
      cilia of over-confluent and perinuclear regions of sub-confluent cells.
      Furthermore, KIF3B mediated functional modulation of purified PC2 channels by FPC
      in a planer lipid bilayer electrophysiology system. The FPC C-terminus
      substantially stimulated PC2 channel activity in the presence of KIF3B, whereas
      FPC or KIF3B alone had no effect. Taken together, we discovered that kinesin-2 is
      a linker between PC2 and FPC and mediates the regulation of PC2 channel function
      by FPC. Our study may be important for elucidating common molecular pathways for
      PKD of different genotypes.

PMID- 17008359
TI  - Neighbourhood effects and the real world beyond randomized community trials: a
      reply to Michael J Oakes.

PMID- 17008360
TI  - Is tuberculin skin testing useful to diagnose latent tuberculosis in BCG
      vaccinated children?
AB  - BACKGROUND: The tuberculin skin test (TST) is the most commonly used tool to
      detect infection with Mycobacterium tuberculosis. We sought to determine whether
      tuberculin skin testing is useful to detect latent infection by M. tuberculosis
      in a population that was vaccinated with the Bacille Calmette Guerin (BCG)
      vaccine. METHODS: We performed a cross-sectional study during October 2000
      February 2001, enrolling first and sixth graders from a random, stratified sample
      of public elementary schools in Orizaba, Veracruz, Mexico. We assessed the
      relationship between sociodemographic and epidemiological information, BCG scars,
      and TST reactivity. RESULTS: There were 858 children enrolled in the study with a
      completed questionnaire and TST result. The prevalence of a positive TST result
      (> or =10 mm) was 12.4%. Controlling for BCG scar, age, and other
      characteristics, close contact with pulmonary tuberculosis patients (odds ratio
      6.56, 95% confidence interval 2.05-21.07, P = 0.001) was independently associated
      with TST reactivity. CONCLUSIONS: TST results helped identify children in a BCG
      vaccinated population who had recent exposure to persons with pulmonary
      tuberculosis, were probably infected with M. tuberculosis, and could benefit from
      treatment for their latent tuberculosis infection.

PMID- 17008361
TI  - Parental age and risk of childhood cancers: a population-based cohort study from
      Sweden.
AB  - BACKGROUND: Frequent germ line cells mutations were previously demonstrated to be
      associated with aging. This suggests a higher incidence of childhood cancer among
      children of older parents. A population-based cohort study of parental ages and
      other prenatal risk factors for five main childhood cancers was performed with
      the use of a linkage between several national-based registries. METHODS: In
      total, about 4.3 million children with their parents, born between 1961 and 2000,
      were included in the study. Multivariate Poisson regression was used to obtain
      the incidence rate ratios (IRR) and 95% confidence interval (CI). Children <5
      years of age and children 5-14 years of age were analysed independently. RESULTS:
      There was no significant result for children 5-14 years of age. For children <5
      years of age, maternal age were associated with elevated risk of retinoblastoma
      (oldest age group's IRR = 2.39, 95%CI = 1.17-4.85) and leukaemia (oldest age
      group's IRR = 1.44, 95%CI = 1.01-2.05). Paternal age was significantly associated
      with leukaemia (oldest age group's IRR = 1.31, 95%CI = 1.04-1.66). For central
      nervous system cancer, the effect of paternal age was found to be significant
      (oldest age group's IRR = 1.69, 95%CI = 1.21-2.35) when maternal age was included
      in the analysis. CONCLUSION: Our findings indicate that advanced parental age
      might be associated with an increased risk of early childhood cancers.

PMID- 17008362
TI  - Factors associated with HIV sero-status in young rural South African women:
      connections between intimate partner violence and HIV.
AB  - BACKGROUND: This paper aims to describe factors associated with HIV sero-status
      in young, rural South African women and the relationship between intimate partner
      violence (IPV) and HIV. METHODS: A total of 1295 sexually active female
      volunteers, aged 15-26, from 70 villages were recruited to participate in a
      cluster randomized controlled trial of an HIV behavioural intervention. The main
      measures were HIV sero-status, and IPV and sexual practices measured using a
      questionnaire administered during baseline interviews. RESULTS: About 12.4% of
      women had HIV and 26.6% had experienced more than one episode of physical or
      sexual IPV. After adjusting for age, HIV infection was associated with having
      three or more past year partners [odds ratio (OR) 2.39; 95% confidence interval
      (95% CI) 1.48-3.85], sex in past 3 months (OR 3.33; 95% CI 1.87-5.94), a partner
      three or more years older (OR 1.69; 95% CI 1.16-2.48), and a more educated
      partner (OR 1.91; 95% CI 1.30-2.78). IPV was associated with HIV in two-way
      analyses (OR 1.56; 95% CI 1.08-2.23), but the effect was non-significant after
      adjusting for HIV risk behaviours. The experience of IPV was strongly associated
      with past year partner numbers, time of last sex, and partner's education; it was
      also marginally associated with partner age difference. Adverse experiences in
      childhood, including sexual abuse, increased the likelihood of having more past
      year partners (OR 1.43; 95% CI 1.21-1.69). CONCLUSIONS: IPV was strongly
      associated with most of the identified HIV risk factors. Our findings provide
      further evidence of links between IPV and HIV among women and the importance of
      joint prevention.

PMID- 17008363
TI  - Pre-irradiation and post-irradiation fading of the Harshaw 8841 TLD in different
      environmental conditions.
AB  - The pre-irradiation and post-irradiation fading of a commercially available
      LiF:Mg,Cu,P thermoluminescent detector (TLD)-the Harshaw 8841 TLD-have been
      assessed. The Harshaw 8841 TLD comprises three TLD-700H chips (99.7% 7LiF and
      0.03% 6LiF by weight) and one TLD-600H chip (4.4% 7LiF and 95.6% 6LiF by weight).
      Pre-irradiation and post-irradiation fading were measured for storage times up to
      164 d and three different storage temperatures (-8, 25 and 50 degrees C).
      Dosemeters were irradiated in a mixed photon-neutron field so that the fading
      behaviour of the photon and neutron signals could be studied. The TLD-700H and
      TLD-600H chips exhibited complex changes in sensitivity and signal that depended
      on storage time, storage temperature and the type of radiation to which the chips
      had been exposed. However, the magnitudes of these changes in sensitivity and
      signal were relatively small. TLD-600H and TLD-700H, therefore, exhibit good
      stability of sensitivity and signal.

PMID- 17008364
TI  - Irritable bowel syndrome in twins: genes and environment.
AB  - BACKGROUND AND AIMS: Both environmental and genetic factors may contribute to
      irritable bowel syndrome (IBS). Nutrition in fetal life, an early environmental
      factor, seems to influence the development of chronic diseases later in life,
      such as coronary heart disease, hypertension, and non-insulin diabetes. This
      population based twin study evaluated the association between intrauterine
      growth, measured by weight and gestational age, and IBS. Structural equation
      analyses were conducted to analyse genetic and environmental sources of variation
      in liability to IBS. METHODS: A postal questionnaire was sent to 12 700 Norwegian
      twins born between 1967 and 1979. The questionnaire included a checklist of 31
      illnesses and symptoms, including IBS. The influence of birth weight on
      developing IBS was tested in four weight groups. Disease discordant monozygotic
      (MZ) pairs were analysed to test the association between intrauterine growth and
      IBS. RESULTS: Concordance for IBS was significantly greater (p = 0.011) in
      monozygotic (22.4%) than in dizygotic (9.1%) twins. The heritability of IBS was
      estimated to be 48.4% among females. Birth weight below 1500 g (adjusted odds
      ratio 2.4 (95% confidence interval 1.1, 5.3)) contributed significantly to the
      development of IBS, which appeared 7.7 years earlier than in higher weight
      groups. In the MZ group with birth weights lower than 2500 g, twins with IBS were
      significantly lighter than twins without disease (190.6 g; p = 0.02). CONCLUSION:
      The present study demonstrates that restricted fetal growth has a significant
      influence on the development of IBS later in life. Weight below 1500 g influences
      age at onset. Genetic contribution appears to be important for IBS among females.

PMID- 17008365
TI  - Life expectancy of adult liver allograft recipients in the UK.
AB  - BACKGROUND: Liver transplantation is a very successful therapy for those with end
      stage disease. Although there are numerous data on patient and graft survival
      after liver transplantation, life expectancy and possible loss of life (compared
      with a normal matched population) in those who survive remains unknown. AIMS: To
      assess the life expectancy and life years lost of adult liver allograft
      recipients, compared with an age and sex matched UK population to provide
      patients with more information and to improve the use of a scarce resource.
      METHODS: Using the National Transplant Database held by UK Transplant, on over
      3600 adult liver allograft recipients transplanted between 1985 and 2003, we
      analysed survival of all adults who survived more than six months after
      transplantation and compared survival after transplantation with national age and
      sex matched controls to assess life years lost. RESULTS: Estimated median
      survival time of the analysis cohort of 2702 adult liver allograft recipients was
      22.2 years (95% confidence interval 19.3-25.6), with an estimated loss of seven
      life years compared with an age and sex matched population. CONCLUSIONS: Overall,
      female recipients have a longer life expectancy and lose fewer life years than
      male recipients. While younger recipients have a longer life expectancy, they
      also lose more life years. Those transplanted for cancer, hepatitis C virus
      infection, and alcoholic liver disease had the greatest loss of life years.

PMID- 17008366
TI  - Use of routinely collected amniotic fluid for whole-genome expression analysis of
      polygenic disorders.
AB  - BACKGROUND: Neural tube defects related to polygenic disorders are the second
      most common birth defects in the world, but no molecular biologic tests are
      available to analyze the genes involved in the pathomechanism of these disorders.
      We explored the use of routinely collected amniotic fluid to characterize the
      differential gene expression profiles of polygenic disorders. METHODS: We used
      oligonucleotide microarrays to analyze amniotic fluid samples obtained from
      pregnant women carrying fetuses with neural tube defects diagnosed during
      ultrasound examination. The control samples were obtained from pregnant women who
      underwent routine genetic amniocentesis because of advanced maternal age (>35
      years). We also investigated specific folate-related genes because maternal
      periconceptional folic acid supplementation has been found to have a protective
      effect with respect to neural tube defects. RESULTS: Fetal mRNA from amniocytes
      was successfully isolated, amplified, labeled, and hybridized to whole-genome
      transcript arrays. We detected differential gene expression profiles between
      cases and controls. Highlighted genes such as SLA, LST1, and BENE might be
      important in the development of neural tube defects. None of the specific folate
      related genes were in the top 100 associated transcripts. CONCLUSIONS: This pilot
      study demonstrated that a routinely collected amount of amniotic fluid (as small
      as 6 mL) can provide sufficient RNA to successfully hybridize to expression
      arrays. Analysis of the differences in fetal gene expressions might help us
      decipher the complex genetic background of polygenic disorders.

PMID- 17008367
TI  - Molecular system bioenergetics: regulation of substrate supply in response to
      heart energy demands.
AB  - This review re-evaluates regulatory aspects of substrate supply in heart. In
      aerobic heart, the preferred substrates are always free fatty acids, and workload
      induced increase in their oxidation is observed at unchanged global levels of
      ATP, phosphocreatine and AMP. Here, we evaluate the mechanisms of regulation of
      substrate supply for mitochondrial respiration in muscle cells, and show that a
      system approach is useful also for revealing mechanisms of feedback signalling
      within the network of substrate oxidation and particularly for explaining the
      role of malonyl-CoA in regulation of fatty acid oxidation in cardiac muscle. This
      approach shows that a key regulator of fatty acid oxidation is the energy demand.
      Alterations in malonyl-CoA would not be the reason for, but rather the
      consequence of, the increased fatty acid oxidation at elevated workloads, when
      the level of acetyl-CoA decreases due to shifts in the kinetics of the Krebs
      cycle. This would make malonyl-CoA a feedback regulator that allows acyl-CoA
      entry into mitochondrial matrix space only when it is needed. Regulation of
      malonyl-CoA levels by AMPK does not seem to work as a master on-off switch, but
      rather as a modulator of fatty acid import.

PMID- 17008368
TI  - Novelty exploration elicits a reversal of acute stress-induced modulation of
      hippocampal synaptic plasticity in the rat.
AB  - Acute behavioural stress has been recognized as a strong influence on the
      inducibility of hippocampal long-term synaptic plasticity. We have reported
      previously that in adult male rats, acute behavioural stress impairs long-term
      potentiation (LTP) but enhances long-term depression (LTD) in the hippocampal CA1
      region. In this study we report that the effects of stress on LTP and LTD were
      reversed when animals were introduced into a novel 'stimulus-rich' environment
      immediately after the stress. Novelty exploration-induced reversal of stress
      effects was prevented when the animals were given the NMDA receptor antagonist D
      (-)-2-amino-5-phosphonopentanoic acid, the cholinergic antagonist atropine and
      the protein phosphatase (PP) 2B inhibitors cyclosporin A and cypermethrin, but
      not the alpha1-adrenergic antagonist prazosin, the beta-adrenergic antagonist
      propranolol or the PP1/2A inhibitor okadaic acid, respectively before being
      subjected to the novel environment. In addition, the ability of novelty
      exploration to reverse the stress effects was mimicked by a direct application of
      the cholinergic agonist carbachol. Exposure to the novel environment following
      stress was accompanied by the activation of both PP2B and striatal-enriched
      tyrosine phosphatase (STEP). Taken together, these findings suggest that the
      activation of the cholinergic system and, in turn, the triggering of an NMDA
      receptor-mediated activation of PP2B to increase STEP activity appear to mediate
      the novelty exploration-induced reversal of stress-related modulation of
      hippocampal long-term synaptic plasticity.

PMID- 17008369
TI  - Computational principles of sensorimotor control that minimize uncertainty and
      variability.
AB  - Sensory and motor noise limits the precision with which we can sense the world
      and act upon it. Recent research has begun to reveal computational principles by
      which the central nervous system reduces the sensory uncertainty and movement
      variability arising from this internal noise. Here we review the role of optimal
      estimation and sensory filtering in extracting the sensory information required
      for motor planning, and the role of optimal control, motor adaptation and
      impedance control in the specification of the motor output signal.

PMID- 17008370
TI  - Ca2+ sensitivity of regulated cardiac thin filament sliding does not depend on
      myosin isoform.
AB  - Myosin heavy chain (MHC) isoforms in vertebrate striated muscles are
      distinguished functionally by differences in chemomechanical kinetics. These
      kinetic differences may influence the cross-bridge-dependent co-operativity of
      thin filament Ca(2+) activation. To determine whether Ca(2+) sensitivity of
      unloaded thin filament sliding depends upon MHC isoform kinetics, we performed in
      vitro motility assays with rabbit skeletal heavy meromyosin (rsHMM) or porcine
      cardiac myosin (pcMyosin). Regulated thin filaments were reconstituted with
      recombinant human cardiac troponin (rhcTn) and alpha-tropomyosin (rhcTm)
      expressed in Escherichia coli. All three subunits of rhcTn were coexpressed as a
      functional complex using a novel construct with a glutathione S-transferase (GST)
      affinity tag at the N-terminus of human cardiac troponin T (hcTnT) and an
      intervening tobacco etch virus (TEV) protease site that allows purification of
      rhcTn without denaturation, and removal of the GST tag without proteolysis of
      rhcTn subunits. Use of this highly purified rhcTn in our motility studies
      resulted in a clear definition of the regulated motility profile for both fast
      and slow MHC isoforms. Maximum sliding speed (pCa 5) of regulated thin filaments
      was roughly fivefold faster with rsHMM compared with pcMyosin, although speed was
      increased by 1.6- to 1.9-fold for regulated over unregulated actin with both MHC
      isoforms. The Ca(2+) sensitivity of regulated thin filament sliding speed was
      unaffected by MHC isoform. Our motility results suggest that the cellular changes
      in isoform expression that result in regulation of myosin kinetics can occur
      independently of changes that influence thin filament Ca(2+) sensitivity.

PMID- 17008371
TI  - Reversal of diet-induced insulin resistance with a single bout of exercise in the
      rat: the role of PTP1B and IRS-1 serine phosphorylation.
AB  - Lifestyle interventions including exercise programmes are cornerstones in the
      prevention of obesity-related diabetes. In this study, we demonstrate that a
      single bout of exercise inhibits high-fat diet-induced insulin resistance. Diet
      induced obesity (DIO) increased the expression and activity of the protein
      tyrosine phosphatase 1B (PTP1B) and attenuated insulin signalling in
      gastrocnemius muscle of rats, a phenomenon which was reversed by a single session
      of exercise. In addition, DIO was observed to lead to serine phosphorylation of
      insulin receptor substrate 1 (IRS-1), which was also reversed by exercise in
      muscle in parallel with a reduction in c-Jun N-terminal kinase (JNK) activity.
      Thus, acute exercise increased the insulin sensitivity during high-fat feeding in
      obese rats. Overall, these results provide new insights into the mechanism by
      which exercise restores insulin sensitivity.

PMID- 17008372
TI  - Functional segregation of synaptic GABAA and GABAC receptors in goldfish bipolar
      cell terminals.
AB  - The transmission of light responses to retinal ganglion cells is regulated by
      inhibitory input from amacrine cells to bipolar cell (BC) synaptic terminals.
      GABA(A) and GABA(C) receptors in BC terminals mediate currents with different
      kinetics and are likely to have distinct functions in limiting BC output;
      however, the synaptic properties and localization of the receptors are currently
      poorly understood. By recording endogenous GABA receptor currents directly from
      BC terminals in goldfish retinal slices, I show that spontaneous GABA release
      activates rapid GABA(A) receptor miniature inhibitory postsynaptic currents
      (mIPSCs) (predominant decay time constant (tau(decay)), 1.0 ms) in addition to a
      tonic GABA(C) receptor current. The GABA(C) receptor antagonist (1,2,5,6
      tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) has no effect on the
      amplitude or kinetics of the rapid GABA(A) mIPSCs. In addition, inhibition of the
      GAT-1 GABA transporter, which strongly regulates GABA(C) receptor currents in BC
      terminals, fails to reveal a GABA(C) component in the mIPSCs. These data suggest
      that GABA(A) and GABA(C) receptors are highly unlikely to be synaptically
      colocalized. Using non-stationary noise analysis of the mIPSCs, I estimate that
      GABA(A) receptors in BC terminals have a single-channel conductance (gamma) of 17
      pS and that an average of just seven receptors mediates a quantal event. From
      noise analysis of the tonic current, GABA(C) receptor gamma is estimated to be 4
      pS. Identified GABA(C) receptor mIPSCs exhibit a slow decay (tau(decay), 54 ms)
      and are mediated by approximately 42 receptors. The distinct properties and
      localization of synaptic GABA(A) and GABA(C) receptors in BC terminals are likely
      to facilitate their specific roles in regulating the transmission of light
      responses in the retina.

PMID- 17008373
TI  - Interstitial matrix proteins determine hyaluronan reflection and fluid retention
      in rabbit joints: effect of protease.
AB  - Hyaluronan (HA) retention inside the synovial cavity of joints serves diverse
      protective roles. We tested the hypothesis that HA retention is mediated by the
      network of extracellular matrix proteins in the synovial lining. Cannulated
      rabbit knee joints were infused with HA solution with or without pretreatment by
      chymopapain, a collagen-sparing protease. Trans-synovial fluid escape rate was
      measured and, after a period of trans-synovial filtration, samples of intra
      articular fluid and subsynovial fluid were analysed for HA to assess its trans
      synovial ultrafiltration. In control joints, HA ultrafiltration was confirmed by
      postfiltration increases in intra-articular HA concentration (259 +/- 17% of
      infused concentration) and reduced subsynovial concentration (30 +/- 8%; n = 11).
      The proportion of HA molecules reflected by the synovium was 57-75%. Chymopapain
      treatment increased the hydraulic permeability of the synovial lining
      approximately 13-fold, almost abolished the trans-synovial difference in HA
      concentration and reduced the HA reflected fraction to 3-7% (n = 6; P < 0.001,
      ANOVA). Structural studies confirmed that chymopapain treatment depleted the
      matrix of proteoglycans but preserved its collagen. The findings thus demonstrate
      that HA ultrafiltration and synovial hydraulic permeability are determined by the
      network of non-collagen, extracellular matrix proteins. This may be important
      clinically, since protease activity is raised in rheumatoid arthritis, as are HA
      and fluid escape.

PMID- 17008374
TI  - Cell domain-dependent changes in the glutamatergic and GABAergic drives during
      epileptogenesis in the rat CA1 region.
AB  - An increased ratio of the glutamatergic drive to the overall
      glutamatergic/GABAergic drive characterizes the chronic stage of temporal lobe
      epilepsy (TLE), but it is unclear whether this modification is present during the
      latent period that often precedes the epileptic stage. Using the pilocarpine
      model of TLE in rats, we report that this ratio is decreased in hippocampal CA1
      pyramidal cells during the early phase of the latent period (3-5 days post
      pilocarpine). It is, however, increased during the late phase of the latent
      period (7-10 days post pilocarpine), via cell domain-dependent alterations in
      synaptic current properties, concomitant with the occurrence of interictal-like
      activity in vivo. During the late latent period, the glutamatergic drive was
      increased in somata via an enhancement in EPSC decay time constant and in
      dendrites via an increase in EPSC frequency and amplitude. The GABAergic drive
      remained unchanged in the soma but was decreased in dendrites, since the drop off
      in IPSC frequency was more marked than the increase in IPSC kinetics. Theoretical
      considerations suggest that these modifications are sufficient to produce
      interictal-like activity. In epileptic animals, the ratio of the glutamatergic
      drive to the overall synaptic drive was not further modified, despite additional
      changes in synaptic current frequency and kinetics. These results show that the
      global changes to more glutamatergic and less GABAergic activities in the CA1
      region precede the chronic stage of epilepsy, possibly facilitating the
      occurrence and/or the propagation of interictal activity.

PMID- 17008375
TI  - Modelling spinal circuitry involved in locomotor pattern generation: insights
      from the effects of afferent stimulation.
AB  - A computational model of the mammalian spinal cord circuitry incorporating a two
      level central pattern generator (CPG) with separate half-centre rhythm generator
      (RG) and pattern formation (PF) networks has been developed from observations
      obtained during fictive locomotion in decerebrate cats. Sensory afferents have
      been incorporated in the model to study the effects of afferent stimulation on
      locomotor phase switching and step cycle period and on the firing patterns of
      flexor and extensor motoneurones. Here we show that this CPG structure can be
      integrated with reflex circuits to reproduce the reorganization of group I reflex
      pathways occurring during locomotion. During the extensor phase of fictive
      locomotion, activation of extensor muscle group I afferents increases extensor
      motoneurone activity and prolongs the extensor phase. This extensor phase
      prolongation may occur with or without a resetting of the locomotor cycle, which
      (according to the model) depends on the degree to which sensory input affects the
      RG and PF circuits, respectively. The same stimulation delivered during flexion
      produces a temporary resetting to extension without changing the timing of
      following locomotor cycles. The model reproduces this behaviour by suggesting
      that this sensory input influences the PF network without affecting the RG. The
      model also suggests that the different effects of flexor muscle nerve afferent
      stimulation observed experimentally (phase prolongation versus resetting) result
      from opposing influences of flexor group I and II afferents on the PF and RG
      circuits controlling the activity of flexor and extensor motoneurones. The
      results of modelling provide insights into proprioceptive control of locomotion.

PMID- 17008376
TI  - Modelling spinal circuitry involved in locomotor pattern generation: insights
      from deletions during fictive locomotion.
AB  - The mammalian spinal cord contains a locomotor central pattern generator (CPG)
      that can produce alternating rhythmic activity of flexor and extensor
      motoneurones in the absence of rhythmic input and proprioceptive feedback. During
      such fictive locomotor activity in decerebrate cats, spontaneous omissions of
      activity occur simultaneously in multiple agonist motoneurone pools for a number
      of cycles. During these 'deletions', antagonist motoneurone pools usually become
      tonically active but may also continue to be rhythmic. The rhythmic activity that
      re-emerges following a deletion is often not phase shifted. This suggests that
      some neuronal mechanism can maintain the locomotor period when motoneurone
      activity fails. To account for these observations, a simplified computational
      model of the spinal circuitry has been developed in which the locomotor CPG
      consists of two levels: a half-centre rhythm generator (RG) and a pattern
      formation (PF) network, with reciprocal inhibitory interactions between
      antagonist neural populations at each level. The model represents a network of
      interacting neural populations with single interneurones and motoneurones
      described in the Hodgkin-Huxley style. The model reproduces the range of
      locomotor periods and phase durations observed during real locomotion in adult
      cats and permits independent control of the level of motoneurone activity and of
      step cycle timing. By altering the excitability of neural populations within the
      PF network, the model can reproduce deletions in which motoneurone activity fails
      but the phase of locomotor oscillations is maintained. The model also suggests
      criteria for the functional identification of spinal interneurones involved in
      the mammalian locomotor pattern generation.

PMID- 17008377
TI  - Vasomotor sympathetic neural control is maintained during sustained upright
      posture in humans.
AB  - Vasomotor sympathetic activity plays an important role in arterial pressure
      maintenance via the baroreflex during acute orthostasis in humans. If orthostasis
      is prolonged, blood pressure may be supported additionally by humoral factors
      with a possible reduction in sympathetic baroreflex sensitivity. We tested the
      hypothesis that baroreflex control of muscle sympathetic nerve activity (MSNA)
      decreases during prolonged upright posture. MSNA and haemodynamics were measured
      supine and during 45 min 60 deg upright tilt in 13 healthy individuals.
      Sympathetic baroreflex sensitivity was quantified using the slope of the linear
      correlation between MSNA and diastolic pressure during spontaneous breathing. It
      was further assessed as the relationship between MSNA and stroke volume, with
      stroke volume derived from cardiac output (C2H2 rebreathing) and heart rate.
      Total peripheral resistance was calculated from mean arterial pressure and
      cardiac output. We found that MSNA increased from supine to upright (17+/-8
      (S.D.) versus 38+/-12 bursts min-1; P<0.01), and continued to increase to a
      smaller degree during sustained tilt (39+/-11, 41+/-12, 43+/-13 and 46+/-15
      bursts min-1 after 10, 20, 30 and 45 min of tilt; between treatments P<0.01).
      Sympathetic baroreflex sensitivity increased from supine to upright (-292+/-180
      versus -718+/-362 units beat-1 mmHg-1; P<0.01), but remained unchanged as tilting
      continued (-611+/-342 and -521+/-221 units beat-1 mmHg-1 after 20 and 45 min of
      tilt; P=0.49). For each subject, changes in MSNA were associated with changes in
      stroke volume (r=0.88+/-0.13, P<0.05), while total peripheral resistance was
      related to MSNA during 45 min upright tilt (r=0.82+/-0.15, P<0.05). These results
      suggest that the vasoconstriction initiated by sympathetic adrenergic nerves is
      maintained by ongoing sympathetic activation during sustained (i.e. 45 min)
      orthostasis without obvious changes in vasomotor sympathetic neural control.

PMID- 17008378
TI  - Activation of protein kinase C augments T-type Ca2+ channel activity without
      changing channel surface density.
AB  - T-type Ca2+ channels play essential roles in numerous cellular processes.
      Recently, we reported that phorbol-12-myristate-13-acetate (PMA) potently
      enhanced the current amplitude of Cav3.2 T-type channels reconstituted in Xenopus
      oocytes. Here, we have compared PMA modulation of the activities of Cav3.1,
      Cav3.2 and Cav3.3 channels, and have investigated the underlying mechanism. PMA
      augmented the current amplitudes of the three T-type channel isoforms, but the
      fold stimulations and time courses differed. The augmentation effects were not
      mimicked by 4alpha-PMA, an inactive stereoisomer of PMA, but were abolished by
      preincubation with protein kinase C (PKC) inhibitors, indicating that PMA
      augmented T-type channel currents via activation of oocyte PKC. The stimulation
      effect on Cav3.1 channel activity by PKC was mimicked by endothelin when
      endothelin receptor type A was coexpressed with Cav3.1 in the Xenopus oocyte
      system. Pharmacological studies combined with fluorescence imaging revealed that
      the surface density of Cav3.1 T-type channels was not significantly changed by
      activation of PKC. The PKC effect on Cav3.1 was localized to the cytoplasmic II
      III loop using chimeric channels with individual cytoplasmic loops of Cav3.1
      replaced by those of Cav2.1.

PMID- 17008379
TI  - Carotid baroreceptor stimulation alters cutaneous vascular conductance during
      whole-body heating in humans.
AB  - Prior studies investigating carotid baroreflex control of the cutaneous
      vasculature have yielded mixed findings. However, previously used methodological
      and analytical techniques may limit the ability to detect carotid baroreflex
      mediated changes in cutaneous vascular conductance (CVC). The aim of this study
      was to test the hypothesis that dynamic carotid baroreceptor stimulation (i.e. 5
      s trials) using neck pressure (NP, simulated carotid hypotension) and neck
      suction (NS, simulated carotid hypertension) will decrease and increase CVC,
      respectively, during normothermic and whole-body heating conditions in resting
      humans. Data were obtained from nine subjects (age, 31 +/- 2 year). The ratio of
      forearm skin blood flux (laser-Doppler flowmetry) and arterial blood pressure
      (Finapres) was used as an index of CVC. Multiple 5 s trials of NP (+40(Torr)) and
      NS (-60(Torr)), as well as breath-hold/airflow control trials, were applied
      during end-expiratory breath-holds while subjects were normotheric and heat
      stressed (change in core temperature approximately 0.75 degrees C). CVC responses
      to each NP and NS trial were averaged into 1 s intervals during the following
      periods: 3 s prestimulus, 5 s during stimulus, and 5 s poststimulus. Peak CVC
      responses (3 s average) to NP and NS were compared to prestimulus values using
      paired t test. During normothermia, NP decreased CVC by 0.032 +/- 0.007 arbitrary
      units (a.u.) mmHg(-1); (P < 0.05); however, breath-hold/airflow control trials
      resulted in similar decreases in CVC. NS did not change CVC (Delta = 0.002 +/-
      0.005 a.u. mmHg(-1); P = 0.63). During whole-body heating, NP decreased CVC (by
      0.16 +/- 0.04 a.u. mmHg(-1); (P < 0.05), whereas NS increased CVC by 0.07 +/-
      0.03 a.u. mmHg(-1); (P < 0.05). Furthermore, these changes were greater than, or
      directionally different from, the breath-hold/airflow control trials. These
      findings indicate that carotid baroreceptor stimulation elicits dynamic changes
      in CVC and that these changes are more apparent during whole-body heating.

PMID- 17008380
TI  - The ionic stoichiometry of the GLAST glutamate transporter in salamander retinal
      glia.
AB  - Maintaining a low extracellular glutamate concentration in the central nervous
      system is important for terminating synaptic transmission and preventing
      excitotoxic cell death. The stoichiometry of the most abundant glutamate
      transporter, GLT-1, predicts that a very low glutamate concentration,
      approximately 2 nM, should be reached in the absence of glutamate release, yet
      microdialysis measurements give a value of approximately 1 microM. If other
      glutamate transporters had a different stoichiometry, the predicted minimum
      glutamate concentration could be higher, for example if those transporters were
      driven by the cotransport of 2 Na+ (rather than of 3 Na+ as for GLT-1). Here we
      investigated the ionic stoichiometry of the glutamate transporter GLAST, which is
      the major glutamate transporter expressed in the retina and cerebellum, is
      expressed in other adult brain areas at a lower level than GLT-1, and is present
      throughout the brain early in development when expression of GLT-1 is low.
      Glutamate transport by GLAST was found to be driven, as for GLT-1, by the
      cotransport of 3 Na+ and 1 H+ and the counter-transport of 1 K+, suggesting that
      the minimum extracellular glutamate concentration should be similar during
      development and in the adult brain. A less powerful accumulation of glutamate by
      GLAST than by GLT-1 cannot be used to explain the high glutamate concentration
      measured by microdialysis.

PMID- 17008382
TI  - In vivo transcript profiling and phylogenetic analysis identifies suppressor of
      cytokine signaling 2 as a direct signal transducer and activator of transcription
      5b target in liver.
AB  - The GH-activated signal transducer and activator of transcription 5b (STAT5b) is
      an essential regulator of somatic growth. The transcriptional response to STAT5b
      in liver is poorly understood. We have combined microarray-based expression
      profiling and phylogenetic analysis of gene regulatory regions to study the
      interplay between STAT5b and GH in the regulation of hepatic gene expression. The
      acute transcriptional response to GH in vivo after a single pulse of GH was
      studied in the liver of hypophysectomized rats in the presence of either
      constitutively active or a dominant-negative STAT5b delivered by adenoviral gene
      transfer. Genes showing differential expression in these two situations were
      analyzed for the presence of STAT5b binding sites in promoter and intronic
      regions that are phylogenetically conserved between rats and humans. Using this
      approach, we showed that most rapid transcriptional effects of GH in the liver
      are not results of direct actions of STAT5b. In addition, we identified novel
      STAT5b cis regulatory elements in genes such as Frizzled-4, epithelial membrane
      protein-1, and the suppressor of cytokine signaling 2 (SOCS2). Detailed analysis
      of SOCS2 promoter demonstrated its direct transcriptional regulation by STAT5b
      upon GH stimulation. A novel response element was identified within the first
      intron of the human SOCS2 gene composed of an E-box followed by tandem STAT5b
      binding sites, both of which are required for full GH responsiveness. In summary,
      we demonstrate the power of combining transcript profiling with phylogenetic
      sequence analysis to define novel regulatory paradigms.

PMID- 17008381
TI  - Heart repair and stem cells.
AB  - Of the medical conditions currently being discussed in the context of possible
      treatments based on cell transplantation therapy, few have received more
      attention than the heart. Much focus has been on the potential application of
      bone marrow-derived cell preparations, which have already been introduced into
      double-blind, placebo-controlled clinical trials. The consensus is that bone
      marrow may have therapeutic benefit but that this is not based on the ability of
      bone marrow cells to transdifferentiate into cardiac myocytes. Are there
      potential stem cell sources of cardiac myocytes that may be useful in replacing
      those lost or dysfunctional after myocardial infarction? Here, this question is
      addressed with a review of the recent literature.

PMID- 17008383
TI  - Asymmetric cleavage of beta-carotene yields a transcriptional repressor of
      retinoid X receptor and peroxisome proliferator-activated receptor responses.
AB  - beta-Carotene and its metabolites exert a broad range of effects, in part by
      regulating transcriptional responses through specific nuclear receptor
      activation. Symmetric cleavage of beta-carotene can yield 9-cis retinoic acid (9
      cisRA), the natural ligand for the nuclear receptor RXR, the obligate
      heterodimeric partner for numerous nuclear receptor family members. A significant
      portion of beta-carotene can also undergo asymmetric cleavage to yield
      apocarotenals, a series of poorly understood naturally occurring molecules whose
      biologic role, including their transcriptional effects, remains essentially
      unknown. We show here that beta-apo-14'-carotenal (apo14), but not other
      structurally related apocarotenals, represses peroxisome proliferator-activated
      receptors (PPAR) and RXR activation and biologic responses induced by their
      respective agonists both in vitro and in vivo. During adipocyte differentiation,
      apo14 inhibited PPARgamma target gene expression and adipogenesis, even in the
      presence of the potent PPARgamma agonist BRL49653. Apo14 also suppressed known
      PPARalpha responses, including target gene expression and its known
      antiinflammatory effects, but not if PPARalpha agonist stimulation occurred
      before apo14 exposure and not in PPARalpha-deficient cells or mice. Other
      apocarotenals tested had none of these effects. These data extend current views
      of beta-carotene metabolism to include specific apocarotenals as possible
      biologically active mediators and identify apo14 as a possible template for
      designing PPAR and RXR modulators and better understanding modulation of nuclear
      receptor activation. These results also suggest a novel model of molecular
      endocrinology in which metabolism of a parent compound, beta-carotene, may
      alternatively activate (9-cisRA) or inhibit (apo14) specific nuclear receptor
      responses.

PMID- 17008384
TI  - Methylation status of a single CpG locus 3 bases upstream of TATA-box of receptor
      activator of nuclear factor-kappaB ligand (RANKL) gene promoter modulates cell-
      and tissue-specific RANKL expression and osteoclastogenesis.
AB  - Receptor activator of nuclear factor-kappaB ligand (RANKL) expression is tissue
      specific and limited to certain subsets of T-lymphocytes and stromal/osteoblastic
      cells. Even among osteoblasts, RANKL is expressed on about 20% of osteoblasts of
      the normal mouse. To clarify the mechanism of population-specific RANKL
      expression, we analyzed the effect of CpG methylation on its transcription, mRNA
      and protein expression as well as on osteoclastogenesis. Subpopulations of ST2
      cells were used: P9, which expresses RANKL and supports osteoclastogenesis, and
      P16, which does not. By sodium bisulfite mapping, the rate of CpG methylation of
      the -65/+350 region, especially of CpG locus no. 1 three bases upstream of the
      TATA-box, was higher in P16 than in P9 ST2 cells. ChIP and gel shift assay showed
      that methylated CpG locus no. 1 was a target of MeCP2 binding that, in turn,
      blocked the binding of the TATA-box binding protein to the TATA-box. In vitro
      methylation by SssI of the promoter construct reduced its transcriptional
      activity at the steady state and its response to 1alpha,25(OH)2 vitamin D3.
      Conversely, treatment with DNA methylase inhibitor, 5-aza-2'-deoxycytidine,
      significantly restored RANKL expression and osteoclastogenesis in P16 cells.
      Except for primary cultured osteoblasts, CpG locus no. 1 was frequently
      methylated in various normal mouse tissues. We propose that the methylation
      status of the CpG locus three bases upstream of the TATA-box modulates the
      control of cell- and tissue-specific expression of RANKL gene and
      osteoclastogenesis. The heterogeneity of stromal/ osteoblastic cells in response
      to bone-resorbing stimuli may be attributed, in part, to the methylation status
      of the RANKL gene promoter.

PMID- 17008385
TI  - Ligand-selective interdomain conformations of estrogen receptor-alpha.
AB  - Selective estrogen receptor modulators (SERMs) inhibit estrogen activation of the
      estrogen receptor (ER) in some tissues but activate ER in other tissues. These
      tissue-selective actions suggest that SERMs may be identified with tissue
      specificities that would improve the safety of breast cancer and hormone
      replacement therapies. The identification of an improved SERM would be aided by
      understanding the effects of each SERM on the structure and interactions of ER.
      To date, the inability to obtain structures of the full-length ER has limited our
      structural characterization of SERM action to their antiestrogenic effects on the
      isolated ER ligand binding domain. We studied the effects of estradiol and the
      clinically useful SERMs 4-hydroxytamoxifen and fulvestrant on the conformation of
      the full-length ERalpha dimer complex by comparing, in living human breast cancer
      cells, the amounts of energy transfer between fluorophores attached to different
      domains of ERalpha. Estradiol, 4-hydroxytamoxifen, and fulvestrant all promoted
      the rapid formation of ERalpha dimers with equivalent interaction kinetics. The
      amino- and carboxyl-terminal ERalpha domains both contain activation functions
      differentially affected by these ligands, but the positions of only the carboxyl
      termini differed upon binding with estradiol, 4-hydroxytamoxifen, or fulvestrant.
      The association of a specific ERalpha dimer conformation with the binding of
      ligands of different clinical effect will assist the identification of a SERM
      with optimal tissue-selective estrogenic and antiestrogenic activities. These
      studies also provide a roadmap for dissecting important structural and kinetic
      details for any protein complex from the quantitative analysis of energy
      transfer.

PMID- 17008386
TI  - Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans
      cells.
AB  - The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One
      of the major problems of the therapeutical use of nicotinic acid is a strong
      cutaneous vasodilation called flushing, which develops in almost every patient
      taking nicotinic acid. Nicotinic acid-induced flushing has been shown to be
      mediated by the nicotinic acid receptor GPR109A and to involve the formation of
      vasodilatory prostanoids. However, the cellular mechanisms underlying this short
      term effect are unknown. Here, we show that epidermal Langerhans cells are
      essential for the cutaneous flushing response induced by nicotinic acid.
      Langerhans cells respond with an increase in [Ca(2+)](i) to nicotinic acid and
      express prostanoid synthases required for the formation of the vasodilatory
      prostanoids prostaglandin E(2) and prostaglandin D(2). Depletion of epidermal
      Langerhans cells but not of macrophages or dendritic cells abrogates nicotinic
      acid-induced flushing. These data unexpectedly identify epidermal Langerhans
      cells as essential mediators of nicotinic acid-induced flushing and may help to
      generate new strategies to suppress the unwanted effects of nicotinic acid. In
      addition, our results suggest that Langerhans cells besides their immunological
      roles are also involved in the local regulation of dermal blood flow.

PMID- 17008387
TI  - Pyrrolidine dithiocarbamate inhibits induction of immunoproteasome and decreases
      survival in a rat model of amyotrophic lateral sclerosis.
AB  - Pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear transcription factor
      kappa-B (NF-kappaB) and an antioxidant, has beneficial effects in animal models
      of various diseases, including arthritis, brain ischemia, spinal cord injury,
      Alzheimer's disease, and Duchenne muscular dystrophy. Because inflammation and
      oxidative damage are also hallmarks of amyotrophic lateral sclerosis (ALS), we
      studied the effect of oral PDTC treatment on G93A-superoxide dismutase 1 (SOD1)
      transgenic (TG) rat model of human ALS and observed that PDTC treatment
      significantly decreases the survival. PDTC treatment evoked the end stage of the
      disease at 121 +/- 21 days, whereas untreated TG animals reached the end stage at
      141 +/- 13 days (p < 0.01). The DNA binding activity of NF-kappaB was not altered
      in G93A-SOD1 TG rats by PDTC treatment. The copper concentration in the spinal
      cord was increased after PDTC treatment both in G93A-SOD1 TG and wild-type rats,
      suggesting that increased copper may enhance the neurotoxicity of mutant SOD1.
      The amount of ubiquitinated proteins were significantly higher and proteasomal
      activity was decreased in the spinal cords of PDTC-treated TG rats compared with
      other groups, suggesting that PDTC treatment decreases proteasome function.
      Immunoblotting and immunocytochemistry showed that the level of immunoproteasome
      but not constitutive proteasome was increased in glia of G93A-SOD1 TG rats along
      with disease development. PDTC treatment completely blocked the induction of
      immunoproteasome expression without affecting constitutive proteasome. These
      results suggest that PDTC acts as an immunoproteasome inhibitor in mutant SOD1
      rats and that immunoproteasome may help the nervous system to cope with
      deleterious effects of SOD1-G93A mutation.

PMID- 17008388
TI  - Regulation of the homologous two-component systems KvgAS and KvhAS in Klebsiella
      pneumoniae CG43.
AB  - In Klebsiella pneumoniae CG43, deletion of the sensor gene kvgS reduced the kvgAS
      expression in M9 medium with 0.2 mM paraquat, 0.2 mM 2,2-dihydropyridyl, or 300
      mM NaCl. This result shows an autoregulatory role of KvgS and a stress-responsive
      expression of the two-component system (2CS). The kvgS deletion also appeared to
      decrease the expression of kvhAS, paralogous genes of kvgAS. Additionally,
      measurements of the promoter activity in kvgA(-) mutant revealed that KvgA is
      probably an activator for the expression of kvgAS and kvhAS. The subsequent
      electrophoretic mobility shift assay, indicating a specific binding of the
      recombinant KvgA to the putative promoters P(kvgAS) and P(kvhAS), also supported
      an interacting regulation between the 2CSs. In P(kvgAS) and P(kvhAS), the
      presence of RpoS binding elements suggested an RpoS-dependent regulation.
      Nevertheless, the rpoS deletion reduced the expression of kvgAS but increased
      that of kvhAS. Moreover, the kvgA deletion reduced the expression of katG and
      sodC. The overexpression of KvhA altered the susceptibility to fosfomycin and an
      increasing activity of UDP-N-acetylglucosamine enolpyruvyl transferase, the
      target protein of fosfomycin, which suggesting a regulation by KvhA. Taken
      together, these indicated that the two 2CSs probably belong to different
      regulatory circuits of the RpoS regulon.

PMID- 17008389
TI  - Postnatally elevated levels of insulin-like growth factor (IGF)-II fail to rescue
      the dwarfism of IGF-I-deficient mice except kidney weight.
AB  - This study tested whether elevated levels of IGF-II in the postnatal period can
      rescue the dwarfism in IGF-I-deficient mice. Heterozygous Igf1 mutant mice [I(+/
      ) II(wt)] were crossed with heterozygous Igf1 mutant, phosphoenolpyruvate
      carboxykinase promoter IGF-II transgenic mice [I(+/-) II(tg)], and [I(+/+)
      II(wt)], [I(+/+) II(tg)], [I(-/-) II(wt)], and [I(-/-) II(tg)] offspring were
      investigated. IGF-II levels were 11- and 6-fold higher in male and female [I(-/-)
      II(tg)] vs. [I(-/-) II(wt)] animals. Western ligand blot analysis revealed
      markedly reduced activities of 30- and 32-kDa IGF binding proteins (IGFBPs) (most
      likely IGFBP-1 and IGFBP-2) and the 39- to 43-kDa IGFBP-3 double band in serum
      from IGF-I-deficient mice. These binding proteins were partially restored by
      overexpression of IGF-II. Analysis of weight data from the early postnatal period
      until d 60 showed that, in the absence of IGF-I, elevated levels of IGF-II have
      no effect on body weight gain. A detailed analysis of body proportions, bone
      parameters, and organ weights of 60-d-old mice also failed to show effects of IGF
      II with one important exception: in Igf1 mutant and also Igf1 intact male mice,
      IGF-II overexpression significantly increased absolute (+32.4 and +28.6%; P <
      0.01) and relative kidney weights (+29.0 and +22.4%; P < 0.001). These changes in
      kidney weight were associated with reduced phosphorylation of p38 MAPK. In
      summary, our genetic model shows that substantial amounts of IGF-II in the
      circulation do not rescue the postnatal growth deficit of IGF-I-deficient mice
      but increase absolute and relative kidney weights of normal and IGF-I-deficient
      male mice, suggesting a gender-specific role of IGF-II for kidney growth.

PMID- 17008390
TI  - Intravascular glucocorticoid metabolism during inflammation and injury in mice.
AB  - 11beta-hydroxysteroid dehydrogenases (11betaHSDs) catalyze interconversion of 11
      hydroxy-glucocorticoids with inactive 11-keto metabolites. In blood vessel walls,
      loss of 11betaHSD1 is thought to reduce local glucocorticoid concentrations,
      reducing the progression of atheroma and enhancing angiogenesis. Conversely, on
      the basis that 11betaHSD1 is up-regulated approximately 5-fold by inflammatory
      cytokines in cultured human vascular smooth muscle cells, it has been proposed
      that increased 11betaHSD1 during vascular inflammation provides negative feedback
      suppression of inflammation. We aimed to determine whether inflammation and
      injury selectively up-regulate 11betaHSD1 reductase activity in vitro and in vivo
      in intact vascular tissue in mice. In isolated mouse aortae and femoral arteries,
      reductase activity (converting 11-dehydrocorticosterone to corticosterone) was
      approximately 10-fold higher than dehydrogenase activity and was entirely
      accounted for by 11betaHSD1 because it was abolished in vessels from 11betaHSD1(
      /-) mice. Although 11betaHSD1 activity was up-regulated by proinflammatory
      cytokines in cultured murine aortic smooth muscle cells, no such effect was
      evident in intact aortic rings in vitro. Moreover, after systemic inflammation
      induced by ip lipopolysaccharide injection, there was only a modest (18%)
      increase in 11beta-reductase activity in the aorta and no increase in the
      perfused hindlimb. Furthermore, in femoral arteries in which neointimal
      proliferation was induced by intraluminal injury, there was no change in basal
      11betaHSD1 activity or the sensitivity of 11betaHSD1 to cytokine up-regulation.
      We conclude that increased generation of glucocorticoids by 11betaHSD1 in the
      murine vessel wall is unlikely to contribute to feedback regulation of
      inflammation.

PMID- 17008391
TI  - Differential regulation of steroidogenesis by bone morphogenetic proteins in
      granulosa cells: involvement of extracellularly regulated kinase signaling and
      oocyte actions in follicle-stimulating hormone-induced estrogen production.
AB  - In the present study, we investigated the cellular mechanism by which oocytes and
      bone morphogenetic proteins (BMPs) govern FSH-induced steroidogenesis using rat
      primary granulosa cells. BMP-6 and BMP-7 both inhibited FSH- and forskolin (FSK)
      induced progesterone synthesis and reduced cAMP synthesis independent of the
      presence or absence of oocytes. BMP-7 also increased FSH-induced estradiol
      production, and the response was further augmented in the presence of oocytes. In
      contrast, BMP-6 had no impact on estradiol synthesis regardless of the presence
      of oocytes. Because BMP-7 changed neither FSK- nor cAMP-induced estradiol
      production, the BMP-7 action was mediated through a FSH receptor signaling
      mechanism that was independent of cAMP-protein kinase A pathway. Treatment with
      FSH but not cAMP activated ERK1/2 phosphorylation in granulosa cells, which was
      further accelerated by oocytes. A specific ERK inhibitor, U0126, increased
      estradiol production and decreased FSH- and FSK-induced progesterone production
      and cAMP synthesis. This suggests that ERK activation is directly linked to
      inhibition of estradiol synthesis and amplification of cAMP. Moreover, FSH
      induced ERK1/2 phosphorylation was inhibited by BMP-7 but not influenced by BMP
      6. In contrast, BMP signaling including Smad1/5/8 phosphorylation and Id-1
      transcription was up-regulated by FSH and oocytes in granulosa cells through
      inhibition of Smad6/7 expression. Collectively, oocytes enhance FSH-induced MAPK
      activation and BMP signaling in granulosa cells, which leads to differential
      regulation of steroidogenesis elicited by BMPs in the presence of FSH in
      developing follicles.

PMID- 17008392
TI  - Atrial natriuretic peptide, a regulator of nuclear factor-kappaB activation in
      vivo.
AB  - Natriuretic peptides (NPs) comprise a family of vasoactive hormones that play
      important roles in the regulation of cardiovascular and renal homeostasis. Along
      this line, atrial NP (ANP) (international non-proprietary name: carperitide,
      HANP) is an approved drug for the treatment of acute heart failure. In recent
      years, evidence has been given that the NP system possesses a far broader
      biological spectrum than the regulation of blood pressure and volume homeostasis.
      In fact, a substantial amount of in vitro work indicates that ANP affects
      important inflammatory processes and signaling pathways. Quite surprisingly,
      however, no information exists on the in vivo antiinflammatory potential and
      signaling of ANP. We show here that pretreatment of lipopolysaccharide
      (Salmonella abortus equi, 2.5 mg/kg)-challenged mice with ANP (5 microg/kg iv, 15
      min) rapidly inhibits nuclear factor-kappaB activation via inhibition of
      phosphorylation and degradation of the IkappaB-alpha protein. ANP also reduces
      Akt activation upon lipopolysaccharide injection. In ANP-pretreated mice, the
      increase of TNF-alpha serum concentration is markedly prevented; most
      importantly, the survival of these animals improved. These findings demonstrate
      both in vitro and in vivo an antiinflammatory profile of ANP that deserves to be
      further investigated in a therapeutic perspective.

PMID- 17008393
TI  - Effects of obestatin on energy balance and growth hormone secretion in rodents.
AB  - Ghrelin stimulates food intake and adiposity and thereby increases body weight
      (BW) in rodents after central as well as peripheral administration. Recently, it
      was discovered that the gene precursor of ghrelin encoded another secreted and
      bioactive peptide named obestatin. First reports appeared to demonstrate that
      this peptide requires an amidation for its biological activity and acts through
      the orphan receptor, GPR-39. Obestatin was shown to have actions opposite to
      ghrelin on food intake, BW, and gastric emptying. In the present study, we failed
      to observe any effect of obestatin on food intake, BW, body composition, energy
      expenditure, locomotor activity, respiratory quotient, or hypothalamic
      neuropeptides involved in energy balance regulation. In agreement with the first
      report, we were unable to find any effect of obestatin on GH secretion in vivo.
      Moreover, we were unable to find mRNA expression of GPR-39, the putative
      obestatin receptor, in the hypothalamus of rats. Therefore, the results presented
      here do not support a role of the obestatin/GPR-39 system in the regulation of
      energy balance.

PMID- 17008394
TI  - Gut mucosal homeostasis and cellular mediators after severe thermal trauma and
      the effect of insulin-like growth factor-I in combination with insulin-like
      growth factor binding protein-3.
AB  - Increased small bowel epithelial cell apoptosis and decreased cell proliferation
      lead to impairment of gut mucosal integrity and function after thermal injury.
      Impairment of gut integrity is associated with increased bacterial translocation
      and incidence of sepsis. The purpose of this study was to determine whether IGF
      I/IGF binding protein (IGFBP)-3 can improve small bowel homeostasis after injury
      and by which cellular mechanisms these changes occur and to identify changes in
      apoptosis-related genes after burn and the effect of bile acid on small bowel
      epithelial cell apoptosis after burn. Rats sustained a thermal injury and
      received saline or the IGF-I/IGFBP-3 complex. Serum and small intestine were
      taken at 1, 2, 5, and 7 d after injury and serum inflammatory cytokines and
      mucosal apoptosis, proliferation, villous morphology, and apoptotic and
      proliferative mediators were measured. Apoptosis-related gene expression and the
      bile acid pool were determined in separate experiments up to 6 h after burn. Gut
      epithelial cell apoptosis as well as apoptosis-related genes were increased after
      the thermal injury, whereas bile acid secretion was significantly decreased (P <
      0.05). IGF-I/IGFBP-3 significantly improved villous height and cells per villous
      by decreasing small bowel epithelial cell apoptosis and increasing proliferation
      (P < 0.05). Decreased apoptosis was associated with decreased Fas, Fas-ligand,
      and TNF when compared with saline (P < 0.05). A severe thermal injury caused an
      up-regulation of apoptosis and apoptosis-related genes and down-regulation of
      bile acid secretion. IGF-I/IGFBP-3 decreases small bowel epithelial cell
      apoptosis through down-regulation of the Fas pathway, which improves gut mucosal
      integrity after a severe thermal injury.

PMID- 17008395
TI  - Potential antiinflammatory role of insulin via the preferential polarization of
      effector T cells toward a T helper 2 phenotype.
AB  - Hyperglycemia in critical illness is a common complication and a strong
      independent risk factor for morbidity and death. Intensive insulin therapy
      decreases this risk by up to 50%. It is unclear to what extent this benefit is
      due to reversal of glucotoxicity or to a direct effect of insulin, because
      antiinflammatory effects of insulin have already been described, but the
      underlying mechanisms are still poorly understood. The insulin receptor is
      expressed on resting neutrophils, monocytes, and B cells, but is not detectable
      on T cells. However, significant up-regulation of insulin receptor expression is
      observed on activated T cells, which suggests an important role during T cell
      activation. Exogenous insulin in vitro induced a shift in T cell differentiation
      toward a T helper type 2 (Th2)-type response, decreasing the T helper type 1 to
      Th2 ratio by 36%. This result correlated with a corresponding change in cytokine
      secretion, with the interferon-gamma to IL-4 ratio being decreased by 33%. These
      changes were associated with increased Th2-promoting ERK phosphorylation in the
      presence of insulin. Thus, we demonstrate for the first time that insulin
      treatment influences T cell differentiation promoting a shift toward a Th2-type
      response. This effect of insulin in changing T cell polarization may contribute
      to its antiinflammatory role not only in sepsis, but also in chronic inflammation
      associated with obesity and type 2 diabetes.

PMID- 17008396
TI  - NFkappaB1/p50 is not required for tumor necrosis factor-stimulated growth of
      primary mammary epithelial cells: implications for NFkappaB2/p52 and RelB.
AB  - Nuclear factor kappaB (NFkappaB) plays an important role in mammary gland
      development and breast cancer. We previously demonstrated that TNF stimulates
      growth of mammary epithelial cells (MEC) in a physiologically relevant three
      dimensional primary culture system, accompanied by enhanced DNA-binding of the
      NFkappaB p50 homodimer. To further understand the mechanism of TNF-stimulated
      growth of primary MEC, the requirement for NFkappaB1/p50, and the role of cyclin
      D1 in TNF-stimulated growth were examined. TNF induced the formation of DNA
      binding complexes of p50 and p52 with their coactivator bcl3 in MEC nuclear
      extracts. Concomitantly, TNF increased the binding of NFkappaB proteins to the
      kappaB site on the cyclin D1 promoter, and increased expression of cyclin D1 mRNA
      and protein. Using MEC from p50 null mice, we found that p50 was not required for
      TNF-induced growth nor for up-regulation of cyclin D1. However, TNF induced a
      p52/RelB NFkappaB DNA-binding complex in p50 null MEC nuclear extracts. In
      addition, we found that in wild-type MEC, TNF stimulated the occupancy of p52 and
      RelB on the cyclin D1 promoter kappaB site, whereas p50 was present
      constitutively. These data suggest that in wild-type MEC, TNF stimulates the
      interaction of bcl3 with p50 and p52, and the binding of p52, as well as RelB, to
      cyclin D1 promoter kappaB sites, and as a consequence, stimulates the growth of
      MEC. In the absence of p50, p52 and RelB can compensate for p50 in TNF-stimulated
      growth and cyclin D1 induction in MEC.

PMID- 17008397
TI  - A purine analog kinase inhibitor, calcium/calmodulin-dependent protein kinase II
      inhibitor 59, reveals a role for calcium/calmodulin-dependent protein kinase II
      in insulin-stimulated glucose transport.
AB  - Olomoucine is known as a cyclin-dependent kinase inhibitor. We found that
      olomoucine blocked insulin's ability to stimulate glucose transport. It did so
      without affecting the activity of known insulin signaling proteins. To identify
      the olomoucine-sensitive kinase(s), we prepared analogs that could be immobilized
      to an affinity resin to isolate binding proteins. One of the generated analogs
      inhibited insulin-stimulated glucose uptake with increased sensitivity compared
      with olomoucine. The IC(50) for inhibition of insulin-stimulated glucose uptake
      occurred at analog concentrations as low as 0.1 microM. To identify proteins
      binding to the analog, [(35)S]-labeled cell lysates prepared from 3T3-L1
      adipocytes were incubated with analog chemically cross-linked to a resin support
      and binding proteins analyzed by SDS-PAGE. The major binding species was a
      doublet at 50-60 kDa, which was identified as calcium/calmodulin-dependent
      protein kinase II (CaMKII) by N-terminal peptide analysis and confirmed by matrix
      assisted laser desorption ionization-mass spectrometry as the delta- and beta
      like isoforms. To investigate CaMKII involvement in insulin-stimulated glucose
      uptake, 3T3-L1 adipocytes were infected with retrovirus encoding green
      fluorescent protein (GFP)-hemagluttinin tag (HA)-tagged CaMKII wild-type or the
      ATP binding mutant, K42M. GFP-HA-CaMKII K42M cells had less kinase activity than
      cells expressing wild-type GFP-HA-CaMKII. Insulin-stimulated glucose transport
      was significantly decreased (approximately 80%) in GFP-HA-CaMKII K42M cells,
      compared with nontransfected cells, and cells expressing either GFP-HA-CaMKII or
      GFP-HA. There was not a concomitant decrease in insulin-stimulated GLUT4
      translocation in GFP-HA-CaMKII K42M cells when compared with GFP-HA alone.
      However, insulin-stimulated GLUT4 translocation in GFP-HA-CaMKII cells was
      significantly higher, compared with either GFP-HA or GFP-HA-CaMKII K42M cells.
      Our results implicate the involvement of CaMKII in glucose transport in a
      permissive role.

PMID- 17008398
TI  - Thyroid hormone insufficiency during brain development reduces parvalbumin
      immunoreactivity and inhibitory function in the hippocampus.
AB  - Thyroid hormones are necessary for brain development. gamma-Amino-butyric acid
      (GABA)ergic interneurons comprise the bulk of local inhibitory circuitry in
      brain, many of which contain the calcium binding protein, parvalbumin (PV). A
      previous report indicated that severe postnatal hypothyroidism reduces PV
      immunoreactivity (IR) in rat neocortex. We examined PV-IR and GABA-mediated
      synaptic inhibition in the hippocampus of rats deprived of thyroid hormone from
      gestational d 6 until weaning on postnatal d 30. Pregnant dams were exposed to
      propylthiouracil (0, 3, 10 ppm) via the drinking water, which decreased maternal
      serum T(4) by approximately 50-75% and increased TSH. At weaning, T(4) was
      reduced by approximately 70% in offspring in the low-dose group and fell below
      detectable levels in high-dose animals. PV-IR was diminished in the hippocampus
      and neocortex of offspring killed on postnatal d 21, an effect that could be
      reversed by postnatal administration of T(4). Dose-dependent decreases in the
      density of PV-IR neurons were observed in neocortex and hippocampus, with the
      dentate gyrus showing the most severe reductions (50-75% below control counts).
      Altered staining persisted to adulthood despite the return of thyroid hormones to
      control levels. Developmental cross-fostering and adult-onset deprivation studies
      revealed that early postnatal hormone insufficiency was required for an
      alteration in PV-IR. Synaptic inhibition of the perforant path-dentate gyrus
      synapse evaluated in adult offspring, in vivo, revealed dose-dependent reductions
      in paired pulse depression indicative of a suppression of GABA-mediated
      inhibition. These data demonstrate that moderate degrees of thyroid hormone
      insufficiency during the early postnatal period permanently alters interneuron
      expression of PV and compromises inhibitory function in the hippocampus.

PMID- 17008400
TI  - Expression, translation, and localization of a novel, small growth hormone
      variant.
AB  - A novel transcript of the GH gene has been identified in ocular tissues of chick
      embryos. It is, however, unknown whether this transcript (small chicken GH, scGH)
      is translated. This possibility was therefore assessed. The expression of scGH
      mRNA was confirmed by RT-PCR, using primers that amplified a 426-bp cDNA of its
      coding sequence. This cDNA was inserted into an expression plasmid to transfect
      HEK 293 cells, and its translation was shown by specific scGH immunoreactivity in
      extracts of these cells. This immunoreactivity was directed against the unique N
      terminus of scGH and was associated with a protein of 16 kDa, comparable with its
      predicted size. Most of the immunoreactivity detected was, however, associated
      with a 31-kDa moiety, suggesting scGH is normally dimerized. Neither protein was,
      however, present in media of the transfected HEK cells, consistent with scGH's
      lack of a signal sequence. Similar moieties of 16 and 31 kDa were also found in
      proteins extracted from ocular tissues (neural retina, pigmented epithelium,
      lens, cornea, choroid) of embryos, although they were not consistently present in
      vitreous humor. Specific scGH immunoreactivity was also detected in these tissues
      by immunocytochemistry but not in axons in the optic fiber layer or the optic
      nerve head, which were immunoreactive for full-length GH. In summary, we have
      established that scGH expression and translation occurs in ocular tissues of
      chick embryos, in which its localization in the neural retina and the optic nerve
      head is distinct from that of the full-length protein.

PMID- 17008399
TI  - TC10alpha is required for insulin-stimulated glucose uptake in adipocytes.
AB  - Previous studies have suggested that activation of the Rho family member GTPase
      TC10 is necessary but not sufficient for the stimulation of glucose transport by
      insulin. We show here that endogenous TC10alpha is rapidly activated in response
      to insulin in 3T3L1 adipocytes in a phosphatidylinositol 3-kinase-independent
      manner, whereas platelet-derived growth factor was without effect. Knockdown of
      TC10alpha but not TC10beta by RNA interference inhibited insulin-stimulated
      glucose uptake as well as the translocation of the insulin-sensitive glucose
      transporter GLUT4 from intracellular sites to the plasma membrane. In contrast,
      loss of TC10alpha had no effect on the stimulation of Akt by insulin.
      Additionally, knockdown of TC10alpha inhibited insulin-stimulated translocation
      of its effector CIP4. These data indicate that TC10alpha is specifically required
      for insulin-stimulated glucose uptake in adipocytes.

PMID- 17008401
TI  - Pharmacological and x-ray structural characterization of a novel selective
      androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle
      with hypostimulation of prostate in rats.
AB  - A novel, highly potent, orally active, nonsteroidal tissue selective androgen
      receptor (AR) modulator (BMS-564929) has been identified, and this compound has
      been advanced to clinical trials for the treatment of age-related functional
      decline. BMS-564929 is a subnanomolar AR agonist in vitro, is highly selective
      for the AR vs. other steroid hormone receptors, and exhibits no significant
      interactions with SHBG or aromatase. Dose response studies in castrated male rats
      show that BMS-564929 is substantially more potent than testosterone (T) in
      stimulating the growth of the levator ani muscle, and unlike T, highly selective
      for muscle vs. prostate. Key differences in the binding interactions of BMS
      564929 with the AR relative to the native hormones were revealed through x-ray
      crystallography, including several unique contacts located in specific helices of
      the ligand binding domain important for coregulatory protein recruitment. Results
      from additional pharmacological studies effectively exclude alternative
      mechanistic contributions to the observed tissue selectivity of this unique,
      orally active androgen. Because concerns regarding the potential hyperstimulatory
      effects on prostate and an inconvenient route of administration are major
      drawbacks that limit the clinical use of T, the potent oral activity and tissue
      selectivity exhibited by BMS-564929 are expected to yield a clinical profile that
      provides the demonstrated beneficial effects of T in muscle and other tissues
      with a more favorable safety window.

PMID- 17008402
TI  - Conditions for extreme sensitivity of protein diffusion in membranes to cell
      environments.
AB  - We study protein diffusion in multicomponent lipid membranes close to a rigid
      substrate separated by a layer of viscous fluid. The large-distance, long-time
      asymptotics for Brownian motion are calculated by using a nonlinear stochastic
      Navier-Stokes equation including the effect of friction with the substrate. The
      advective nonlinearity, neglected in previous treatments, gives only a small
      correction to the renormalized viscosity and diffusion coefficient at room
      temperature. We find, however, that in realistic multicomponent lipid mixtures,
      close to a critical point for phase separation, protein diffusion acquires a
      strong power-law dependence on temperature and the distance to the substrate H,
      making it much more sensitive to cell environment, unlike the logarithmic
      dependence on H and very small thermal correction away from the critical point.

PMID- 17008403
TI  - Policy strategies to address sustainability of Alaskan boreal forests in response
      to a directionally changing climate.
AB  - Human activities are altering many factors that determine the fundamental
      properties of ecological and social systems. Is sustainability a realistic goal
      in a world in which many key process controls are directionally changing? To
      address this issue, we integrate several disparate sources of theory to address
      sustainability in directionally changing social-ecological systems, apply this
      framework to climate-warming impacts in Interior Alaska, and describe a suite of
      policy strategies that emerge from these analyses. Climate warming in Interior
      Alaska has profoundly affected factors that influence landscape processes
      (climate regulation and disturbance spread) and natural hazards, but has only
      indirectly influenced ecosystem goods such as food, water, and wood that receive
      most management attention. Warming has reduced cultural services provided by
      ecosystems, leading to some of the few institutional responses that directly
      address the causes of climate warming, e.g., indigenous initiatives to the Arctic
      Council. Four broad policy strategies emerge: (i) enhancing human adaptability
      through learning and innovation in the context of changes occurring at multiple
      scales; (ii) increasing resilience by strengthening negative (stabilizing)
      feedbacks that buffer the system from change and increasing options for
      adaptation through biological, cultural, and economic diversity; (iii) reducing
      vulnerability by strengthening institutions that link the high-latitude impacts
      of climate warming to their low-latitude causes; and (iv) facilitating
      transformation to new, potentially more beneficial states by taking advantage of
      opportunities created by crisis. Each strategy provides societal benefits, and we
      suggest that all of them be pursued simultaneously.

PMID- 17008404
TI  - wasted away, a Drosophila mutation in triosephosphate isomerase, causes
      paralysis, neurodegeneration, and early death.
AB  - To identify genes required for maintaining neuronal viability, we screened our
      collection of Drosophila temperature-sensitive paralytic mutants for those
      exhibiting shortened lifespan and neurodegeneration. Here, we describe the
      characterization of wasted away (wstd), a recessive, hypomorphic mutation that
      causes progressive motor impairment, vacuolar neuropathology, and severely
      reduced lifespan. We demonstrate that the affected gene encodes the glycolytic
      enzyme, triosephosphate isomerase (Tpi). Mutations causing Tpi deficiency in
      humans are also characterized by progressive neurological dysfunction,
      neurodegeneration, and early death. In Tpi-deficient flies and humans, a decrease
      in ATP levels did not appear to cause the observed phenotypes because ATP levels
      remained normal. We also found no genetic evidence that the mutant Drosophila Tpi
      was misfolded or involved in aberrant protein-protein associations. Instead, we
      favor the hypothesis that mutations in Tpi lead to an accumulation of
      methylglyoxal and the consequent enhanced production of advanced glycation end
      products, which are ultimately responsible for the death and dysfunction of Tpi
      deficient neurons. Our results highlight an essential protective role of Tpi and
      support the idea that advanced glycation end products may also contribute to
      pathogenesis of other neurological disorders.

PMID- 17008406
TI  - NMR structural and kinetic characterization of a homeodomain diffusing and
      hopping on nonspecific DNA.
AB  - Nonspecific protein-DNA interactions are inherently dynamic and involve both
      diffusion of the protein along the DNA and hopping of the protein from one DNA
      molecule or segment to another. Understanding how gene regulatory proteins
      interact nonspecifically with DNA in terms of both structure and dynamics is
      challenging because the experimental observables are an ensemble average of many
      rapidly exchanging states. By using a variety of NMR spectroscopic techniques,
      including relaxation analysis, paramagnetic relaxation enhancement, and residual
      dipolar couplings, we have characterized structural and kinetic aspects of the
      interaction of the HoxD9 homeodomain with a nonspecific, 24-bp DNA duplex in a
      system in which the protein is not constrained to any particular site. The data
      reveal that HoxD9 binds to nonspecific DNA with the same binding mode and
      orientation as that observed in the specific complex. The mobility, however, of
      Arg side-chains contacting the DNA is increased in the nonspecific complex
      relative to the specific one. The kinetics of intermolecular translocation
      between two different nonspecific DNA molecules have also been analyzed and
      reveal that at high DNA concentrations (such as those present in vivo) direct
      transfer from one nonspecific complex to another nonspecific DNA molecule occurs
      without going through the intermediary of free protein. This finding provides a
      simple mechanism for accelerating the target search in vivo for the specific site
      in a sea of nonspecific sites by permitting more effective sampling of available
      DNA sites as the protein jumps from one segment to another.

PMID- 17008405
TI  - Defective RNA processing enhances RNA silencing and influences flowering of
      Arabidopsis.
AB  - Many eukaryotic cells use RNA-directed silencing mechanisms to protect against
      viruses and transposons and to suppress endogenous gene expression at the
      posttranscriptional level. RNA silencing also is implicated in epigenetic
      mechanisms affecting chromosome structure and transcriptional gene silencing.
      Here, we describe enhanced silencing phenotype (esp) mutants in Arabidopsis
      thaliana that reveal how proteins associated with RNA processing and 3' end
      formation can influence RNA silencing. These proteins were a putative DEAH RNA
      helicase homologue of the yeast PRP2 RNA splicing cofactor and homologues of mRNA
      3' end formation proteins CstF64, symplekin/PTA1, and CPSF100. The last two
      proteins physically associated with the flowering time regulator FY in the 3' end
      formation complex AtCPSF. The phenotypes of the 3' end formation esp mutants
      include impaired termination of the transgene transcripts, early flowering, and
      enhanced silencing of the FCA-beta mRNA. Based on these findings, we propose that
      the ESP-containing 3' end formation complexes prevent transgene and endogenous
      mRNAs from entering RNA-silencing pathways. According to this proposal, in the
      absence of these ESP proteins, these RNAs have aberrant 3' termini. The aberrant
      RNAs would enter the RNA silencing pathways because they are converted into dsRNA
      by RNA-dependent RNA polymerases.

PMID- 17008407
TI  - Direct observation of Bin/amphiphysin/Rvs (BAR) domain-induced membrane curvature
      by means of molecular dynamics simulations.
AB  - The process of membrane curvature generation by BAR (Bin/amphiphysin/Rvs) domains
      is thought to involve the plastering of the negatively charged cell membrane to
      the positively charged concave surface of the BAR domain. Recent work [Peter, B.
      J., et al. (2004) Science, 303,495-499; Masuda, M., et al. (2006) EMBO J. 25,
      2889-2897; and Gallop, J. L., et al. (2006) EMBO J. 25, 2898-2910] has
      demonstrated the importance of the charged, crescent-shaped surface and the N
      terminal amphipathic helices (present in N-BAR domains) for generating membrane
      curvature. These experiments suggest that curvature is generated by the
      synergistic action of the N-terminal helices embedding in the lipid bilayer and
      the charged crescent-shaped dimer acting to "scaffold" membrane curvature. Here,
      we present atomistic molecular dynamics simulations that directly show membrane
      binding to the concave face of N-BAR domains, resulting in the generation of
      local membrane curvature that matches the curvature presented by the BAR domain.
      These simulations provide direct molecular-scale evidence that BAR domains create
      curvature by acting as a scaffold, forcing the membrane to locally adopt the
      intrinsic shape of the BAR domain. We find that BAR domains bind strongly through
      the maximum curvature surface and, additionally, at an orientation that presents
      a lesser degree of curvature, thus enabling N-BAR domains to induce a range of
      local curvatures. Finally, we find that the N-terminal region may play a role in
      biasing the orientations of N-BAR domains on the membrane surface to those that
      favor binding to the concave face and subsequent membrane bending.

PMID- 17008408
TI  - Phosphodiesterase genes are associated with susceptibility to major depression
      and antidepressant treatment response.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) constitute a family of enzymes that
      degrade cAMP and cGMP. Intracellular cyclic nucleotide levels increase in
      response to extracellular stimulation by hormones, neurotransmitters, or growth
      factors and are down-regulated through hydrolysis catalyzed by PDEs, which are
      therefore candidate therapeutic targets. cAMP is a second messenger implicated in
      learning, memory, and mood, and cGMP modulates nervous system processes that are
      controlled by the nitric oxide (NO)/cGMP pathway. To investigate an association
      between genes encoding PDEs and susceptibility to major depressive disorder
      (MDD), we genotyped SNPs in 21 genes of this superfamily in 284 depressed Mexican
      Americans who participated in a prospective, double-blind, pharmacogenetic study
      of antidepressant response, and 331 matched controls. Polymorphisms in PDE9A and
      PDE11A were found to be associated with the diagnosis of MDD. Our data are also
      suggestive of the association between SNPs in other PDE genes and MDD. Remission
      on antidepressants was significantly associated with polymorphisms in PDE1A and
      PDE11A. Thus, we found significant associations with both the diagnosis of MDD
      and remission in response to antidepressants with SNPs in the PDE11A gene. We
      show here that PDE11A haplotype GAACC is significantly associated with MDD. We
      conclude that PDE11A has a role in the pathophysiology of MDD. This study
      identifies a potential CNS role for the PDE11 family. The hypothesis that drugs
      affecting PDE function, particularly cGMP-related PDEs, represent a treatment
      strategy for major depression should therefore be tested.

PMID- 17008409
TI  - CD8+ regulatory T cells generated by neonatal recognition of peripheral self
      antigen.
AB  - In comparison with CD4+ regulatory T cells, the generation and function of
      immunomodulatory CD8+T cells is less well defined. Here we describe the existence
      of regulatory anti-Kb-specific CD8+ T cells that are rendered tolerant during
      neonatal life via antigen contact exclusively on keratinocytes. These regulatory
      T cells maintain tolerance during adulthood as they prevent Kb-specific graft
      rejection by naive CD8+ T cells. Third-party immune responses remain unaffected.
      Up-regulation of TGF-beta1 and granzyme B in the regulatory CD8+ T cell
      population suggests the involvement of these molecules in common suppressive
      pathways shared with CD4+ regulatory T cells. In summary, CD8+ regulatory T cells
      can be induced extrathymically through antigen contact on neonatally accessible
      parenchymal cells and maintain tolerance throughout adult life.

PMID- 17008410
TI  - Operant matching is a generic outcome of synaptic plasticity based on the
      covariance between reward and neural activity.
AB  - The probability of choosing an alternative in a long sequence of repeated choices
      is proportional to the total reward derived from that alternative, a phenomenon
      known as Herrnstein's matching law. This behavior is remarkably conserved across
      species and experimental conditions, but its underlying neural mechanisms still
      are unknown. Here, we propose a neural explanation of this empirical law of
      behavior. We hypothesize that there are forms of synaptic plasticity driven by
      the covariance between reward and neural activity and prove mathematically that
      matching is a generic outcome of such plasticity. Two hypothetical types of
      synaptic plasticity, embedded in decision-making neural network models, are shown
      to yield matching behavior in numerical simulations, in accord with our general
      theorem. We show how this class of models can be tested experimentally by making
      reward not only contingent on the choices of the subject but also directly
      contingent on fluctuations in neural activity. Maximization is shown to be a
      generic outcome of synaptic plasticity driven by the sum of the covariances
      between reward and all past neural activities.

PMID- 17008411
TI  - Celecoxib reduces microvessel density in patients treated with nasopharyngeal
      carcinoma and induces changes in gene expression.
AB  - BACKGROUND: Celecoxib is a selective cyclooxygenase-2 inhibitor with antitumor
      and antiangiogenic activity. We sought to determine pharmacodynamic change in
      tumors of patients with nasopharyngeal carcinoma (NPC) treated with celecoxib.
      METHODS: Tumor biopsies were obtained before and after treatment with celecoxib
      400 mg b.i.d. for 14 days in patients with newly diagnosed, untreated NPC. Tumor
      angiogenesis and cell proliferation were assessed by immunohistochemistry and
      gene expression by microarray analysis. Plasma celecoxib concentrations were
      obtained on days 8 and 14. RESULTS: Paired samples were analyzed in 15 patients.
      Microvessel density was reduced in post-treatment samples and mean celecoxib
      levels reached therapeutic levels. Thirty-five genes (27 down-regulated, eight up
      regulated) were differentially expressed on microarray analysis (p < 0.001). Down
      regulated genes included cell cycle regulation-related (cyclin-dependent kinase
      2, YES1), transcription factor (TRIP-Br2), whereas the antigen processing and
      presentation-related gene HLA-DM B was up-regulated. CONCLUSION: Celecoxib
      reduced angiogenesis and induced tumor transcriptional changes. Further
      characterization of these transcriptional changes in vivo is needed to provide
      further insights into the effects of celecoxib in neoplastic tissue. Our findings
      provide a rationale for clinical studies aimed at assessing the efficacy of
      celecoxib in the treatment of NPC.

PMID- 17008412
TI  - Multidrug-resistance-associated protein 1 (Mrp1) is probably not required for
      murine Th cell activation.
AB  - Previously, we have demonstrated that multidrug-resistance-associated protein 1
      (Mrp1) represents an activation marker for murine Th1 cells and is constitutively
      expressed by Th2 cells. Using the inhibitor MK571, we and others also suggested
      that Mrp1 is necessary for Th cell activation. However, herein, we show that Mrp1
      deficient Th cells can be differentiated to a similar extent to Th1 and Th2 cells
      in vitro and, upon re-stimulation, produce comparable amounts of IL-2, IFNgamma
      and IL-4. Mrp1-deficient mice are equally susceptible than wild-type mice to
      infection with the protozoan parasite Leishmania major, a well-respected model
      for in vivo Th1 and Th2 cell differentiation. Intriguingly, MK571 is able to
      completely block activation of Mrp1-deficient Th cells. Most likely, therefore,
      the molecule relevant for Th cell activation which is blocked by MK571 is
      different from Mrp1. While these results are compatible with our previously
      reported data on Mrp1 expression, they contradict our previous conclusions about
      Mrp1 function in murine Th1 cells as well as those published in a very recent
      report in this journal on human Th cells.

PMID- 17008413
TI  - Behavioral influences on cortical neuronal responses to optic flow.
AB  - Optic flow selectively activates neurons in medial superior temporal (MST)
      cortex. We find that many MST neurons yield larger and more selective responses
      when the optic flow guides a subsequent eye movement. Smaller, less selective
      responses are seen when optic flow is preceded by a flashed precue that guides
      eye movements. Selectivity can decrease by a third (32%) after a flashed precue
      is presented at a peripheral location as a small spot specifying the target
      location of the eye movement. Smaller decreases in selectivity (18%) occur when
      the precue is presented centrally with its shape specifying the target location.
      Shape precues presented centrally, but not linked to specific target locations,
      do not appear to alter optic flow selectivity. The effects of spatial precueing
      can be reversed so that the precue leads to larger and more selective optic flow
      responses: A flashed precue presented as a distracter before behaviorally
      relevant optic flow is associated with larger optic flow responses and a 45%
      increase in selectivity. Together, these findings show that spatial precues can
      decrease or increase the size and selectivity of optic flow responses depending
      on the associated behavioral contingencies.

PMID- 17008415
TI  - Measuring a doctor's performance: personality, health and well-being.

PMID- 17008418
TI  - Time cost associated with smoking at work highlighted by baseline survey of
      employees participating in a workplace smoking cessation programme.

PMID- 17008419
TI  - Exposure to loud noise and risk of acoustic neuroma.

PMID- 17008420
TI  - Mutations in olfactory signal transduction genes are not a major cause of human
      congenital general anosmia.
AB  - Anosmia affects the western world population, mostly the elderly, reaching to 5%
      in subjects over the age of 45 years and strongly lowering their quality of life.
      A smaller minority (about 0.01%) is born without a sense of smell, afflicted with
      congenital general anosmia (CGA). No causative genes for human CGA have been
      identified yet, except for some syndromic cases such as Kallman syndrome. In
      mice, however, deletion of any of the 3 main olfactory transduction components
      (guanidine triphosphate binding protein, adenylyl cyclase, and the cyclic
      adenosine monophosphate-gated channel) causes profound reduction of physiological
      responses to odorants. In an attempt to identify human CGA-related mutations, we
      performed whole-genome linkage analysis in affected families, but no significant
      linkage signals were observed, probably due to the small size of families
      analyzed. We further carried out direct mutation screening in the 3 main
      olfactory transduction genes in 64 unrelated anosmic individuals. No potentially
      causative mutations were identified, indicating that transduction gene variations
      underlie human CGA rarely and that mutations in other genes have to be
      identified. The screened genes were found to be under purifying selection,
      suggesting that they play a crucial functional role not only in olfaction but
      also potentially in additional pathways.

PMID- 17008421
TI  - N-glycolylneuraminic acid xenoantigen contamination of human embryonic and
      mesenchymal stem cells is substantially reversible.
AB  - Human embryonic and mesenchymal stem cell therapies may offer significant benefit
      to a large number of patients. Recently, however, human embryonic stem cell lines
      cultured on mouse feeder cells were reported to be contaminated by the xeno
      carbohydrate N-glycolylneuraminic acid (Neu5Gc) and considered potentially unfit
      for human therapy. To determine the extent of the problem of Neu5Gc contamination
      for the development of stem cell therapies, we investigated whether it also
      occurs in cells cultured on human feeder cells and in mesenchymal stem cells,
      what are the sources of contamination, and whether the contamination is
      reversible. We found that N-glycolylneuraminic acid was present in embryonic stem
      cells cultured on human feeder cells, correlating with the presence of Neu5Gc in
      components of the commercial serum replacement culture medium. Similar
      contamination occurred in mesenchymal stem cells cultured in the presence of
      fetal bovine serum. The results suggest that the Neu5Gc is present in both
      glycoprotein and lipid-linked glycans, as detected by mass spectrometric analysis
      and monoclonal antibody staining, respectively. Significantly, the contamination
      was largely reversible in the progeny of both cell types, suggesting that
      decontaminated cells may be derived from existing stem cell lines. Although major
      complications have not been reported in the clinical trials with mesenchymal stem
      cells exposed to fetal bovine serum, the immunogenic contamination may
      potentially be reflected in the viability and efficacy of the transplanted cells
      and thus bias the published results. Definition of safe culture conditions for
      stem cells is essential for future development of cellular therapies.

PMID- 17008422
TI  - Differentiation potential of parthenogenetic embryonic stem cells is improved by
      nuclear transfer.
AB  - Parthenogenesis is the process by which an oocyte develops into an embryo without
      being fertilized by a spermatozoon. Although such embryos lack the potential to
      develop to full term, they can be used to establish parthenogenetic embryonic
      stem (pES) cells for autologous cell therapy in females without needing to
      destroy normally competent embryos. Unfortunately, the capacity for further
      differentiation of these pES cells in vivo is very poor. In this study, we
      succeeded in improving the potential of pES cells using a nuclear transfer (NT)
      technique. The original pES cell nuclei were transferred into enucleated oocytes,
      and the resulting NT embryos were used to establish new NT-pES cell lines. We
      established 84 such lines successfully (78% from blastocysts, 12% from oocytes).
      All examined cell lines were positive for several ES cell markers and had a
      normal extent of karyotypes, except for one original pES cell line and its NT-pES
      cell derivatives, in which all nuclei were triploid. The DNA methylation status
      of the differentially methylated domain H19 and differentially methylated region
      IG did not change after NT. However, the in vivo and in vitro differentiation
      potentials of NT-pES cells were significantly (two to five times) better than the
      original pES cells, judged by the production of chimeric mice and by in vitro
      differentiation into neuronal and mesodermal cell lines. Thus, NT could be used
      to improve the potential of pES cells and may enhance that of otherwise poor
      quality ES cells. It also offers a new tool for studying epigenetics.

PMID- 17008423
TI  - Basal cells of the human adult airway surface epithelium retain transit
      amplifying cell properties.
AB  - In numerous airway diseases, such as cystic fibrosis, the epithelium is severely
      damaged and must regenerate to restore its defense functions. Although the human
      airway epithelial stem cells have not been identified yet, we have suggested
      recently that epithelial stem/progenitor cells exist among both human fetal basal
      and suprabasal cell subsets in the tracheal epithelium. In this study, we
      analyzed the capacity of human adult basal cells isolated from human adult airway
      tissues to restore a well-differentiated and functional airway epithelium. To
      this end, we used the human-specific basal cell markers tetraspanin CD151 and
      tissue factor (TF) to separate positive basal cells from negative columnar cells
      with a FACSAria cell sorter. Sorted epithelial cells were seeded into epithelium
      denuded rat tracheae that were grafted subcutaneously in nude mice and on
      collagen-coated porous membranes, where they were grown at the air-liquid
      interface. Sorted basal and columnar populations were also analyzed for their
      telomerase activity, a specific transit-amplifying cell marker, by the telomeric
      repeat amplification protocol assay. After cell sorting, the pure and viable
      CD151/TF-positive basal cell population proliferated on plastic and adhered on
      epithelium-denuded rat tracheae, as well as on collagen-coated porous membranes,
      where it was able to restore a fully differentiated mucociliary and functional
      airway epithelium, whereas viable columnar negative cells did not. Telomerase
      activity was detected in the CD151/TF-positive basal cell population, but not in
      CD151/TF-negative columnar cells. These results demonstrate that human adult
      basal cells are at least airway surface transit-amplifying epithelial cells.

PMID- 17008424
TI  - The cell surface glycosphingolipids SSEA-3 and SSEA-4 are not essential for human
      ESC pluripotency.
AB  - Pluripotent cells can be isolated from the human blastocyst and maintained in
      culture as self-renewing, undifferentiated, human ESCs (hESCs). These cells are a
      valuable model of human development in vitro and are the focus of substantial
      research aimed at generating differentiated populations for cellular therapies.
      The extracellular markers that have been used to characterize hESCs are primarily
      carbohydrate epitopes on proteoglycans or sphingolipids, such as stage-specific
      embryonic antigen (SSEA)-3 and -4. The expression of SSEA-3 and -4 is tightly
      regulated during preimplantation development and on hESCs. Although this might
      imply a molecular function in undifferentiated cells, it has not yet been tested
      experimentally. We used inhibitors of sphingolipid and glycosphingolipid (GSL)
      biosynthesis to block the generation of SSEA-3 and -4 in hESCs. Depletion of
      these antigens and their precursors was confirmed using immunostaining, flow
      cytometry, and tandem mass spectroscopy. Transcriptional analysis,
      immunostaining, and differentiation in vitro and in teratomas indicated that
      other properties of pluripotency were not noticeably affected by GSL depletion.
      These experiments demonstrated that the GSLs recognized as SSEA-3 and -4 do not
      play critical functional roles in maintaining the pluripotency of hESCs, but
      instead suggested roles for this class of molecules during cellular
      differentiation.

PMID- 17008425
TI  - N-Cadherin is expressed by putative stem/progenitor cells and melanocytes in the
      human limbal epithelial stem cell niche.
AB  - Corneal epithelial stem cells are known to be localized to the basal layer of the
      limbal epithelium, providing a model system for epithelial stem cell biology;
      however, the mechanisms regarding the maintenance of these stem cells in their
      specialized niche remain poorly understood. N-cadherin is a member of the classic
      cadherin family and has previously been demonstrated to be expressed by
      hematopoietic stem cells. In the present study, we demonstrate that N-cadherin is
      expressed by putative stem/progenitor cells, as well as melanocytes, in the human
      limbal epithelial stem cell niche. In addition, we demonstrate that upon in vitro
      culture using 3T3 feeder layers, loss of N-cadherin expression occurs with cell
      proliferation. These results indicate that N-cadherin may be a critical cell-to
      cell adhesion molecule between corneal epithelial stem/progenitor cells and their
      corresponding niche cells in the limbal epithelium.

PMID- 17008426
TI  - Survivin identifies keratinocyte stem cells and is downregulated by anti-beta1
      integrin during anoikis.
AB  - Survivin belongs to the family of inhibitor of apoptosis proteins and is involved
      in regulation of cell death as well as cell division. Here, we show that wild
      type (WT) survivin is expressed in a subpopulation of basal keratinocytes in
      normal human skin at the cytoplasmic level. WT survivin is highly expressed in
      keratinocyte stem cells (KSCs), whereas its mRNA level decreases in transit
      amplifying (TA) cells and disappears in postmitotic (PM) cells. Likewise, WT
      survivin protein is expressed in KSCs, almost undetectable in TA cells, and
      absent in PM cells. Real time polymerase chain reaction demonstrates that the
      putative antiapoptotic isoforms survivin-2B and survivin-DeltaEx3 are expressed
      at the highest levels in KSCs, whereas they tend to decrease in TA cells and
      disappear in PM cells. On the contrary, the putative proapoptotic variants of
      survivin, survivin-3B, and survivin-2alpha tend to be high in PM and TA cells and
      are almost absent in KSCs. By confocal microscopy, survivin is predominantly
      expressed at the nuclear level in KSCs, which proliferate significantly better
      than TA cells, which, in turn, express mostly cytosolic WT survivin. Blocking
      beta1 integrin signal downregulates WT survivin mRNA and protein expression and
      induces apoptosis (anoikis) in KSCs. On the other hand, inhibition of beta1
      integrin upregulates mRNA expression of survivin-2alpha. Taken together, these
      results indicate that survivin identifies human KSCs. Expression of nuclear
      survivin could reflect the different behavior between KSCs in vitro and in vivo,
      in terms of proliferation. Finally, survivin could be part of the "niche"
      protection by preventing anoikis in KSCs.

PMID- 17008427
TI  - Antibodies to stem cell marker antigens reduce engraftment of hematopoietic stem
      cells.
AB  - Hematopoietic stem cells (HSCs) have enormous potential for use in
      transplantation and gene therapy. However, the frequency of repopulating HSCs is
      often very low; thus, highly effective techniques for cell enrichment and
      maintenance are required to obtain sufficient cell numbers for therapeutic use
      and for studies of HSC physiology. Common methods of HSC enrichment use
      antibodies recognizing HSC surface marker antigens. Because antibodies are known
      to alter the physiology of other cell types, we investigated the effect of such
      enrichment strategies on the physiology and lineage commitment of HSCs. We sorted
      HSCs using a method that does not require antibodies: exclusion of Hoechst 33342
      to isolate side population (SP) cells. To elucidate the effect of antibody
      binding on this HSC population, we compared untreated SP cells with SP cells
      treated with the Sca-1(+)c-Kit(+)Lin(-) (SKL) antibody cocktail prior to SP
      sorting. Our findings revealed that HSCs incubated with the antibody cocktail had
      decreased expression of the stem cell-associated genes c-Kit, Cd34, Tal-1, and
      Slamf1 relative to untreated SP cells or to cells treated with polyclonal isotype
      control antibodies. Moreover, SKL antibodies induced cycling in SP cells and
      diminished their ability to confer long-term hematopoietic engraftment in
      lethally irradiated mice. Taken together, these data suggest that antibody-based
      stem cell isolation procedures can have negative effects on HSC physiology.

PMID- 17008428
TI  - Stem/progenitor cell-specific enhanced green fluorescent protein expression
      driven by the endogenous Mcm2 promoter.
AB  - Previous studies have demonstrated expression of the minichromosome maintenance
      protein Mcm2 in cells that remain competent to divide, including stem/progenitor
      cells of the subventricular zone (SVZ) within the brain. Here, a transgenic mouse
      line in which the Mcm2 gene drives expression of enhanced green fluorescent
      protein (EGFP) was constructed by insertion of an internal ribosomal entry site
      (IRES)-EGFP cassette into the last exon of the gene, 3' to the stop codon. In
      these mice, expression of EGFP is observed in the SVZ and several other tissues
      with high proliferative activity, including the spleen, intestine, hair
      follicles, and bone marrow. These observations suggest that EGFP fluorescence in
      this mouse line provides an index of the proliferative capacity of different
      tissues. Immunohistological analysis demonstrates a direct concordance between
      expression of EGFP and Mcm2, consistent with a transcriptional level
      downregulation of Mcm2 expression in postmitotic cells. To test the utility of
      EGFP expression for recovery of live cells retaining the capacity to divide, EGFP
      expressing and -nonexpressing cells from bone marrow and brain were isolated from
      an adult Mcm2(IRES-EGFP) mouse by fluorescence-activated cell sorting and assayed
      for clonal growth. The EGFP-positive fraction contained the entire clonogenic
      population of the bone marrow and greater than 90% of neurosphere-forming cells
      from the brain. Brain-derived clonogenic cells were shown to remain competent to
      differentiate towards all three neural lineages. These studies demonstrate that
      the Mcm2(IRES-EGFP) transgenic line constructed here can be used for recovery of
      proliferation competent cells from different tissue types.

PMID- 17008429
TI  - Placental growth factor-1 potentiates hematopoietic progenitor cell mobilization
      induced by granulocyte colony-stimulating factor in mice and nonhuman primates.
AB  - The complex hematopoietic effects of placental growth factor (PlGF) prompted us
      to test in mice and nonhuman primates the mobilization of peripheral blood
      progenitor cells (PBPCs) elicited by recombinant mouse PlGF-2 (rmPlGF-2) and
      recombinant human PlGF-1 (rhPlGF-1). PBPC mobilization was evaluated by assaying
      colony-forming cells (CFCs), high-proliferative potential-CFCs (HPP-CFCs), and
      long-term culture-initiating cells (LTC-ICs). In mice, both rmPlGF-2 and rhPlGF-1
      used as single agents failed to mobilize PBPCs, whereas the combination of rhPlGF
      1 and granulocyte colony-stimulating factor (rhG-CSF) increased CFCs and LTC-ICs
      per milliliter of blood by four- and eightfold, respectively, as compared with
      rhG-CSF alone. rhPlGF-1 plus rhG-CSF significantly increased matrix
      metalloproteinase-9 plasma levels over rhG-CSF alone, suggesting a mechanistic
      explanation for rhPlGF-1/rhG-CSF synergism. In rhesus monkeys, rhPlGF-1 alone had
      no mobilization effect, whereas rhPlGF-1 (260 microg/kg per day) plus rhG-CSF
      (100 microg/kg per day) increased rhG-CSF-elicited mobilization of CFCs, HPP
      CFCs, and LTC-ICs per milliliter of blood by 5-, 7-, and 15-fold, respectively.
      No specific toxicity was associated with the administration of rhPlGF-1 alone or
      in combination. In conclusion, our data demonstrate that rhPlGF-1 significantly
      increases rhG-CSF-elicited hematopoietic mobilization and provide a preclinical
      rationale for evaluating rhPlGF-1 in the clinical setting.

PMID- 17008430
TI  - A comparison of neural differentiation and retinal transplantation with bone
      marrow-derived cells and retinal progenitor cells.
AB  - Retinal progenitor cells (RPCs) are immature precursors that can differentiate
      into retinal neurons, including photoreceptors. Recently, it has been reported
      that bone marrow-derived cells may also be capable of differentiation into cells
      of central nervous system lineage, including retinal neurons. We compared these
      two cell types to evaluate their potential as a source of cells for retinal
      transplantation. Marrow stromal cells (MSCs) and macrophages were isolated from
      enhanced green fluorescence protein mice. MSCs were cultured with brain-derived
      neurotrophic factor, nerve growth factor, and basic fibroblast growth factor to
      induce neuronal differentiation. RPCs were cultured under the same conditions or
      with 10% fetal bovine serum. Neuronal marker expression was examined and compared
      between MSCs and RPCs. MSCs, macrophages, and RPCs were also cultured with
      explanted retinas from rhodopsin knockout mice to study their potential for
      retinal integration. MSCs expressed neuronal and retina-specific markers by
      reverse transcription-polymerase chain reaction and immunocytochemistry. Both
      types of cells migrated into retinal explants and expressed neurofilament 200,
      glial fibrillary acidic protein, protein kinase C-alpha, and recoverin. RPCs
      expressed rhodopsin, a photoreceptor marker we never detected in MSCs. A majority
      of bone marrow derived-macrophages differentiated into cells that resembled
      microglia, rather than neural cells, in the explanted retina. This study shows
      that RPCs are likely to be a preferred cell type for retinal transplantation
      studies, compared with MSCs. However, MSCs may remain an attractive candidate for
      autologous transplantation.

PMID- 17008431
TI  - Detection threshold for inspiratory resistive loads and respiratory-related
      evoked potentials.
AB  - The relationship between detection threshold of inspiratory resistive loads and
      the peaks of the respiratory-related evoked potential (RREP) is unknown. It was
      hypothesized that the short-latency and long-latency peaks of the RREP would only
      be elicited by inspiratory loads that exceeded the detection threshold. The
      detection threshold for inspiratory resistive loads was measured in healthy
      subjects with inspiratory-interruption or onset load presentations. In a separate
      protocol, the RREPs were recorded with resistive loads that spanned the detection
      threshold. The loads were presented in stimulus attend and ignore sessions. Onset
      and interruption load presentations had the same resistive load detection
      threshold. The P(1), N(f), and N(1) peaks of the RREP were observed with loads
      that exceeded the detection threshold in both attend and ignore conditions. The
      P(300) was present with loads that exceeded the detection threshold only in the
      attend condition. No RREP components were elicited with subthreshold loads. The
      P(1), N(f), and P(300) amplitudes varied with resistive load magnitude. The
      results support the hypothesis that there is a resistive load threshold for
      eliciting the RREPs. The amplitude of the RREP peaks vary as a function of load
      magnitude. The cognitive P(300) RREP peak is present only for detectable loads
      and when the subject attends to the stimulus. The absence of the RREP with loads
      below the detection threshold and the presence of the RREP elicited by
      suprathreshold loads are consistent with the gating of these neural measures of
      respiratory mechanosensory information processing.

PMID- 17008432
TI  - Intrinsic and antigen-induced airway hyperresponsiveness are the result of
      diverse physiological mechanisms.
AB  - Airway hyperresponsiveness (AHR) is a defining feature of asthma. We have
      previously shown, in mice sensitized and challenged with antigen, that AHR is
      attributable to normal airway smooth muscle contraction with exaggerated airway
      closure. In the present study we sought to determine if the same was true for
      mice known to have intrinsic AHR, the genetic strain of mice, A/J. We found that
      A/J mice have AHR characterized by minimal increase in elastance following
      aerosolized methacholine challenge compared with mice (BALB/c) that have been
      antigen sensitized and challenged [concentration that evokes 50% change in
      elastance (PC(50)): 22.9 +/- 5.7 mg/ml for A/J vs. 3.3 +/- 0.4 mg/ml for antigen
      challenged and -sensitized mice; P < 0.004]. Similar results were found when
      intravenous methacholine was used (PC(30) 0.22 +/- 0.08 mg/ml for A/J vs. 0.03 +/
      0.004 mg/ml for antigen-challenged and -sensitized mice). Computational model
      analysis revealed that the AHR in A/J mice is dominated by exaggerated airway
      smooth muscle contraction and that when the route of methacholine administration
      was changed to intravenous, central airway constriction dominates. Absorption
      atelectasis was used to provide evidence of the lack of airway closure in A/J
      mice. Bronchoconstriction during ventilation with 100% oxygen resulted in a mean
      9.8% loss of visible lung area in A/J mice compared with 28% in antigen
      sensitized and -challenged mice (P < 0.02). We conclude that the physiology of
      AHR depends on the mouse model used and the route of bronchial agonist
      administration.

PMID- 17008434
TI  - Multifarious microarray-based gene expression patterns in response to exercise.

PMID- 17008435
TI  - MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle
      hypertrophy.
AB  - MicroRNAs (miRNAs) are a class of highly conserved, noncoding RNAs involved in
      posttranscriptional gene regulation. A small number of muscle-specific miRNAs
      have been identified and shown to have a role in myoblast proliferation and
      differentiation as well as embryonic muscle growth. The primary objective of the
      present study was to determine the expression level of the muscle-specific miRNAs
      in the soleus and plantaris muscles and whether their expression in the plantaris
      was altered in response to functional overload. Of the miRNAs examined, only
      miRNA-206 was differentially expressed between soleus and plantaris muscles, as
      reflected by the sevenfold higher expression in the soleus for both the primary
      miRNA (pri-miRNA) and mature miRNA (miR). Following 7 days of functional
      overload, transcript levels for both pri-miRNA-1-2 and pri-miRNA-133a-2 increased
      by approximately 2-fold, whereas pri-miRNA-206 levels were elevated 18.3-fold. In
      contrast, expression of miR-1 and miR-133a were downregulated by approximately
      50% following overload. The discrepancy between pri-miRNA and miR expression
      following overload was not explained by a change in the expression of components
      of the miRNA biogenesis pathway, since Drosha and Exportin-5 transcript levels
      were significantly increased by 50% in response to functional overload, whereas
      Dicer expression remained unchanged. These results are the first to report
      alterations in expression of muscle-specific miRNAs in adult skeletal muscle and
      suggest miRNAs may have a role in the adaptation to functional overload.

PMID- 17008436
TI  - Fiber type-specific muscle glycogen sparing due to carbohydrate intake before and
      during exercise.
AB  - The effect of carbohydrate intake before and during exercise on muscle glycogen
      content was investigated. According to a randomized crossover study design, eight
      young healthy volunteers (n = 8) participated in two experimental sessions with
      an interval of 3 wk. In each session subjects performed 2 h of constant-load
      bicycle exercise ( approximately 75% maximal oxygen uptake). On one occasion
      (CHO), they received carbohydrates before ( approximately 150 g) and during (1
      g.kg body weight(-1).h(-1)) exercise. On the other occasion they exercised after
      an overnight fast (F). Fiber type-specific relative glycogen content was
      determined by periodic acid Schiff staining combined with immunofluorescence in
      needle biopsies from the vastus lateralis muscle before and immediately after
      exercise. Preexercise glycogen content was higher in type IIa fibers [9.1 +/- 1 x
      10(-2) optical density (OD)/microm(2)] than in type I fibers (8.0 +/- 1 x 10(-2)
      OD/microm(2); P < 0.0001). Type IIa fiber glycogen content decreased during F
      from 9.6 +/- 1 x 10(-2) OD/microm(2) to 4.5 +/- 1 x 10(-2) OD/microm(2) (P =
      0.001), but it did not significantly change during CHO (P = 0.29). Conversely, in
      type I fibers during CHO and F the exercise bout decreased glycogen content to
      the same degree. We conclude that the combination of carbohydrate intake both
      before and during moderate- to high-intensity endurance exercise results in
      glycogen sparing in type IIa muscle fibers.

PMID- 17008437
TI  - Effect of endurance exercise training on heart rate onset and heart rate recovery
      responses to submaximal exercise in animals susceptible to ventricular
      fibrillation.
AB  - Both a large heart rate (HR) increase at exercise onset and a slow heart rate
      (HR) recovery following the termination of exercise have been linked to an
      increased risk for ventricular fibrillation (VF) in patients with coronary artery
      disease. Endurance exercise training can alter cardiac autonomic regulation.
      Therefore, it is possible that this intervention could restore a more normal HR
      regulation in high-risk individuals. To test this hypothesis, HR and HR
      variability (HRV, 0.24- to 1.04-Hz frequency component; an index of cardiac vagal
      activity) responses to submaximal exercise were measured 30, 60, and 120 s after
      exercise onset and 30, 60, and 120 s following the termination of exercise in
      dogs with healed myocardial infarctions known to be susceptible (n = 19) to VF
      (induced by a 2-min coronary occlusion during the last minute of a submaximal
      exercise test). These studies were then repeated after either a 10-wk exercise
      program (treadmill running, n = 10) or an equivalent sedentary period (n = 9).
      After 10 wk, the response to exercise was not altered in the sedentary animals.
      In contrast, endurance exercise increased indexes of cardiac vagal activity such
      that HR at exercise onset was reduced (30 s after exercise onset: HR pretraining
      179 +/- 8.4 vs. posttraining 151.4 +/- 6.6 beats/min; HRV pretraining 4.0 +/- 0.4
      vs. posttraining 5.8 +/- 0.4 ln ms(2)), whereas HR recovery 30 s after the
      termination of exercise increased (HR pretraining 186 +/- 7.8 vs. posttraining
      159.4 +/- 7.7 beats/min; HRV pretraining 2.4 +/- 0.3 vs. posttraining 4.0 +/- 0.6
      ln ms(2)). Thus endurance exercise training restored a more normal HR regulation
      in dogs susceptible to VF.

PMID- 17008438
TI  - Similar acute molecular responses to equivalent volumes of isometric,
      lengthening, or shortening mode resistance exercise.
AB  - The present study was undertaken to test the hypothesis that the contraction mode
      of action [static-isometric (Iso), shortening-concentric (Con), or lengthening
      eccentric (Ecc)] used to stress the muscle provides a differential mechanical
      stimulus eliciting greater or lesser degrees of anabolic response at the
      initiation of a resistance training program. We performed an acute resistance
      training study in which different groups of rodents completed four training
      sessions in either the Iso, Con, or Ecc mode of contraction under conditions of
      activation and movement specifically designed to elicit equivalent volumes of
      force accumulation. The results of this experiment indicate that the three modes
      of contraction produced nearly identical cell signaling, indicative of an
      anabolic response involving factors such as increased levels of mRNA for IGF-I,
      procollagen III alpha1, decreased myostatin mRNA, and increased total RNA
      concentration. The resulting profiles collectively provide evidence that pure
      mode of muscle action, in and of itself, does not appear to be a primary variable
      in determining the efficacy of increased loading paradigms with regard to the
      initiation of selected muscle anabolic responses.

PMID- 17008439
TI  - Cerebral blood flow autoregulation in early experimental S. pneumoniae
      meningitis.
AB  - We studied cerebral blood flow (CBF) autoregulation and intracranial pressure
      (ICP) during normo- and hyperventilation in a rat model of Streptococcus
      pneumoniae meningitis. Meningitis was induced by intracisternal injection of S.
      pneumoniae. Mean arterial blood pressure (MAP), ICP, cerebral perfusion pressure
      (CPP, defined as MAP - ICP), and laser-Doppler CBF were measured in anesthetized
      infected rats (n = 30) and saline-inoculated controls (n = 30). CPP was either
      incrementally reduced by controlled hemorrhage or increased by intravenous
      norepinephrine infusion. Twelve hours postinoculation, rats were studied solely
      during normocapnia, whereas rats studied after 24 h were exposed to either
      normocapnia or to acute hypocapnia. In infected rats compared with control rats,
      ICP was unchanged at 12 h but increased at 24 h postinoculation (not significant
      and P < 0.01, respectively); hypocapnia did not lower ICP compared with
      normocapnia. Twelve hours postinoculation, CBF autoregulation was lost in all
      infected rats but preserved in all control rats (P < 0.01). Twenty-four hours
      after inoculation, 10% of infected rats had preserved CBF autoregulation during
      normocapnia compared with 80% of control rats (P < 0.01). In contrast, 60% of the
      infected rats and 100% of the control rats showed an intact CBF autoregulation
      during hypocapnia (P < 0.05 for the comparison of infected rats at normocapnia
      vs. hypocapnia). In conclusion, CBF autoregulation is lost both at 12 and at 24 h
      after intracisternal inoculation of S. pneumoniae in rats. Impairment of CBF
      autoregulation precedes the increase in ICP, and acute hypocapnia may restore
      autoregulation without changing the ICP.

PMID- 17008440
TI  - Neuromechanical control of upper airway patency during sleep.
AB  - Obstructive sleep apnea is caused by pharyngeal occlusion due to alterations in
      upper airway mechanical properties and/or disturbances in neuromuscular control.
      The objective of the study was to determine the relative contribution of
      mechanical loads and dynamic neuromuscular responses to pharyngeal collapse
      during sleep. Sixteen obstructive sleep apnea patients and sixteen normal
      subjects were matched on age, sex, and body mass index. Pharyngeal
      collapsibility, defined by the critical pressure, was measured during sleep. The
      critical pressure was partitioned between its passive mechanical properties
      (passive critical pressure) and active dynamic responses to upper airway
      obstruction (active critical pressure). Compared with normal subjects, sleep
      apnea patients demonstrated elevated mechanical loads as demonstrated by higher
      passive critical pressures [-0.05 (SD 2.4) vs. -4.5 cmH2O (SD 3.0), P = 0.0003].
      Dynamic responses were depressed in sleep apnea patients, as suggested by failure
      to lower their active critical pressures [-1.6 (SD 3.5) vs. -11.1 cmH2O (SD 5.3),
      P < 0.0001] in response to upper airway obstruction. Moreover, elevated
      mechanical loads placed some normal individuals at risk for sleep apnea. In this
      subset, dynamic responses to upper airway obstruction compensated for mechanical
      loads and maintained airway patency by lowering the active critical pressure. The
      present study suggests that increased mechanical loads and blunted neuromuscular
      responses are both required for the development of obstructive sleep apnea.

PMID- 17008441
TI  - Heterogeneity of responses to orthostatic stress in homozygous twins.
AB  - Early analysis into the role of genetics on cardiovascular regulation has been
      accomplished by comparing blood pressure and heart rate in homozygous twins
      during unstressed, resting physiological conditions. However, many variables,
      including cognitive and environmental factors, contribute to the regulation of
      cardiovascular hemodynamics. Therefore, the purpose of this study was to
      determine the hemodynamic response of identical twins to an orthostatic stress,
      ranging from supine rest to presyncope. Heart rate, arterial blood pressure,
      middle cerebral artery blood velocity, an index of cerebrovascular resistance,
      cardiac output, total peripheral resistance, and end-tidal carbon dioxide were
      measured in 16 healthy monozygotic twin pairs. Five minutes of supine resting
      baseline data were collected, followed by 5 min of 60 degrees head-up tilt. After
      5 min of head-up tilt, lower body negative pressure was applied in increments of
      10 mmHg every 3 min until the onset of presyncope, at which time the subject was
      returned to the supine position for a 5-min recovery period. The data indicate
      that cardiovascular regulation under orthostatic stress demonstrates a
      significant degree of variance between identical twins, despite similar
      orthostatic tolerance. As the level of stress increases, so does the difference
      in the cardiovascular response within a twin pair. The elevated variance with
      increasing stress may be due to an increase in the role of environmental factors,
      as the influential role of genetics nears a functional limit. Therefore, although
      orthostatic tolerance times were very similar between identical twins, the
      mechanism involved in sustaining cardiovascular function during increasing stress
      was different.

PMID- 17008442
TI  - The severity of respiratory syncytial virus bronchiolitis in young infants in the
      United Arab Emirates.
AB  - Respiratory syncytial virus (RSV) respiratory infections are very common during
      infancy and account for the majority of hospitalizations during the fall and
      winter seasons. Patients vary in the severity of their illnesses, with most
      hospitalized patients needing oxygen and intravenous fluids. The objective of
      this study was to assess in hospitalized patients the severity of the disease in
      relation to age. We compared children who were <90 days old with children who
      were >90 days old for the duration of oxygen therapy, maximum oxygen
      concentration used, duration of stay and duration of intravenous fluids. We
      conducted a retrospective case review of national children <2 years admitted to
      the pediatric ward at Sheikh Khalifa Medical City with RSV proven
      bronchiolitis/pneumonia over a 3-month period from 1 September to 30 November
      2001. Morbidity for group 1 (birth-90 days) and group 2 (91 days-2 years) was
      compared by the Mann-Whitney U-test using duration of oxygen therapy, maximum
      oxygen concentration used, duration of stay and duration of intravenous fluids.
      Multiple regression for duration of oxygen therapy was tested using the following
      risk factors as predictors: age group (1 or 2), previous ventilation,
      bronchopulmonary dysplasia (BPD) and prematurity. A total of 89 patients were
      admitted during this period. The mean age (SD) of group 1 (n = 28) and group 2 (n
      = 61) was 46.35 (25.57) days and 275.67 (156.79) days, respectively. The only
      statistically significant difference using the Mann-Whitney U-test was detected
      for duration of oxygen between the groups (p = 0.002). Using multiple regression,
      only age group acted as a predictor for duration of oxygen therapy (p < 0.001).
      This implies that the youngest children, group 1, are at a risk for prolonged
      oxygen therapy. Four patients from group 1 were admitted to the intensive care
      unit, of which two received ventilatory support. RSV respiratory infections
      affect infants <3 months old in a more severe form than older infants. Even
      though overall duration of stay was similar for both groups, young infants who in
      fact did require oxygen had a more protracted and severe illness compared with
      the older infants. This was evidenced by their longer duration of oxygen and more
      frequent need to be managed in the intensive care unit.

PMID- 17008443
TI  - Vaccination against tuberculosis.

PMID- 17008444
TI  - Requirement for the gravity-controlled transport of auxin for a negative
      gravitropic response of epicotyls in the early growth stage of etiolated pea
      seedlings.
AB  - Gravity-controlled transport of auxin was studied for a negative gravitropic
      response in the early growth stage of etiolated pea (Pisum sativum L. cv. Alaska)
      seedlings, in which epicotyl bending was observed near the cotyledon nodes of the
      seedlings grown continuously from seeds germinated in a horizontal or an inclined
      position. Increased expression of an auxin-inducible gene, PsIAA4/5, was observed
      in the elongated side of epicotyls grown in a horizontal or an inclined position.
      Regardless of the conditions of seed germination, polar auxin transport in the
      proximal side of the first internodes of the seedlings was significantly higher
      than in the distal side. Polar auxin transport in the proximal side of epicotyls
      grown in an inclined position was significantly lower than in those grown in a
      horizontal position. In contrast, lateral auxin distribution from the proximal to
      distal sides in epicotyls grown in an inclined position was significantly higher
      than in epicotyls grown in a horizontal position. Accumulation of PsPIN1 mRNA
      encoding a putative auxin efflux facilitator, which was observed in vascular
      tissue, cortex and epidermis in the proximal and distal sides of epicotyls, was
      markedly influenced by gravistimulation. These results strongly suggest that
      gravistimulation induces changeable polar auxin transport and one-way lateral
      auxin distribution in epicotyls as well as asymmetric auxin accumulation in the
      proximal and distal sides of epicotyls, resulting in a negative gravitropic
      response of epicotyls in the early growth stage of pea seedlings.

PMID- 17008445
TI  - A dual role for 7-dehydrocholesterol reductase in regulating Hedgehog signalling?

PMID- 17008447
TI  - The bHLH transcription factor hand2 is essential for noradrenergic
      differentiation of sympathetic neurons.
AB  - The basic helix-loop-helix transcription factor Hand2, together with Ascl1,
      Phox2a, Phox2b and Gata2/Gata3, is induced by bone morphogenetic proteins in
      neural crest-derived precursor cells during sympathetic neuron generation. Hand2
      overexpression experiments and the analysis of its function at the Dbh promotor
      implicated Hand2 in the control of noradrenergic gene expression. Using the
      zebrafish hand2 deletion mutant hands off, we have now investigated the
      physiological role of hand2 in the development of sympathetic ganglia. In hands
      off mutant embryos, sympathetic precursor cells aggregate to form normal
      sympathetic ganglion primordia characterized by the expression of phox2b, phox2a
      and the achaete-scute family member zash1a/ascl1. The expression of the
      noradrenergic marker genes th and dbh is strongly reduced, as well as the
      transcription factors gata2 and tfap2a (Ap-2alpha). By contrast, generic neuronal
      differentiation seems to be unaffected, as the expression of elavl3 (HuC) is not
      reduced in hands off sympathetic ganglia. These results demonstrate in vivo an
      essential and selective function of hand2 for the noradrenergic differentiation
      of sympathetic neurons, and implicates tfap2a and gata2 as downstream effectors.

PMID- 17008448
TI  - Schnurri transcription factors from Drosophila and vertebrates can mediate Bmp
      signaling through a phylogenetically conserved mechanism.
AB  - Bone Morphogenetic Proteins (Bmps) are secreted growth factors that play crucial
      roles in animal development across the phylogenetic spectrum. Bmp signaling
      results in the phosphorylation and nuclear translocation of Smads, downstream
      signal transducers that bind DNA. In Drosophila, the zinc finger protein Schnurri
      (Shn) plays a key role in signaling by the Bmp2/Bmp4 homolog Decapentaplegic
      (Dpp), by forming a Shn/Smad repression complex on defined promoter elements in
      the brinker (brk) gene. Brk is a transcriptional repressor that downregulates Dpp
      target genes. Thus, brk inhibition by Shn results in the upregulation of Dpp
      responsive genes. We present evidence that vertebrate Shn homologs can also
      mediate Bmp responsiveness through a mechanism similar to Drosophila Shn. We find
      that a Bmp response element (BRE) from the Xenopus Vent2 promoter drives Dpp
      dependent expression in Drosophila. However, in sharp contrast to its activating
      role in vertebrates, the frog BRE mediates repression in Drosophila. Remarkably,
      despite these opposite transcriptional polarities, sequence changes that abolish
      cis-element activity in Drosophila also affect BRE function in Xenopus. These
      similar cis requirements reflect conservation of trans-acting factors, as human
      Shn1 (hShn1; HIVEP1) can interact with Smad1/Smad4 and assemble an hShn1/Smad
      complex on the BRE. Furthermore, both Shn and hShn1 activate the BRE in Xenopus
      embryos, and both repress brk and rescue embryonic patterning defects in shn
      mutants. Our results suggest that vertebrate Shn proteins function in Bmp signal
      transduction, and that Shn proteins recruit coactivators and co-repressors in a
      context-dependent manner, rather than acting as dedicated activators or
      repressors.

PMID- 17008449
TI  - The yolk syncytial layer regulates myocardial migration by influencing
      extracellular matrix assembly in zebrafish.
AB  - The roles of extra-embryonic tissues in early vertebrate body patterning have
      been extensively studied, yet we know little about their function during later
      developmental events. Here, we analyze the function of the zebrafish extra
      embryonic yolk syncytial layer (YSL) specific transcription factor, Mtx1, and
      find that it plays an essential role in myocardial migration. Downregulating the
      function of Mtx1 in the YSL leads to cardia bifida, a phenotype in which the
      myocardial cells fail to migrate to the midline. Mtx1 in the extra-embryonic YSL
      appears to regulate the embryonic expression of fibronectin, a gene previously
      implicated in myocardial migration. We further show dosage-sensitive genetic
      interactions between mtx1 and fibronectin. Based on these data, we propose that
      the extra-embryonic YSL regulates myocardial migration, at least in part by
      influencing fibronectin expression and subsequent assembly of the extracellular
      matrix in embryonic tissues.

PMID- 17008450
TI  - Characterization and function of the bHLH-O protein XHes2: insight into the
      mechanisms controlling retinal cell fate decision.
AB  - Neurons and glial cells differentiate from common multipotent precursors in the
      vertebrate retina. We have identified a novel member of the hairy/Enhancer of
      split [E(spl)] gene family in Xenopus, XHes2, as a regulator to bias retinal
      precursor cells towards a glial fate. XHes2 expression is predominantly
      restricted to sensory organ territories, including the retina. Using in vivo
      lipofection in the optic vesicle, we found that XHes2 overexpression dramatically
      increases gliogenesis at the expense of neurogenesis. This increase in glial
      cells correlates with a delayed cell cycle withdrawal of some retinal
      progenitors. In addition, birthdating experiments suggest that XHes2 deviates
      some early born cell types towards a glial fate that would normally have given
      rise to neurons. Conversely, a significant inhibition of glial differentiation is
      observed upon XHes2 loss of function. The gliogenic activity of XHes2 relies on
      its ability to inhibit neuronal differentiation by at least two distinct
      mechanisms: it not only negatively regulates XNgnr1 and NeuroD transcription, but
      it also physically interacts with a subset of proneural bHLH proteins.

PMID- 17008451
TI  - The prevention of colitis by E Prostanoid receptor 4 agonist through enhancement
      of epithelium survival and regeneration.
AB  - Inflammatory bowel disease (IBD) is often triggered and/or exacerbated by
      nonsteroidal anti-inflammatory drugs (NSAIDs). Among various prostanoids affected
      by NSAIDs, prostaglandin E2 (PGE2), in particular, seems to play critical roles
      in IBD via the EP4 receptor, one of the four PGE2 receptor subtypes (EP1-4). An
      EP4 agonist, [[3-[[(1R,2S,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxy-4-[3
      (methoxymethyl)phenyl]-1-butenyl]-5-oxocyclopentyl]thio]propyl]thio]-acetic acid,
      C22H30O6S2 (ONO-AE1-329), for example, when topically applied, has been reported
      to ameliorate typical colitis symptoms by suppressing the production of cytotoxic
      cytokines in the dextran sodium sulfate (DSS)-induced colitis model. EP4 agonists
      are also known, however, for their ability to protect epithelial cells from
      apoptosis in vitro, which may contribute to the protection of mucosal barrier
      functions. To investigate this potential application, we have tested another EP4
      selective agonist in the DSS-indomethacin mouse colitis model. 7-[2-(3-Hydroxy-4
      phenyl-but-1-enyl)-6-oxo-piperidin-1-yl]-heptanoic acid methyl ester, C23H33NO4
      (AGN205203), an analog from the 8-azapiperidinone series of EP4 agonists, is
      metabolically and chemically more stable than the ONO agonist, because of its
      lack of oxidizable sulfur atoms in the alpha-chain and of 11-OH group, a
      potential source of beta-elimination reaction. Treatment of mice subcutaneously
      with AGN205203 at 3 mg/kg/day minimized colitis symptoms, such as weight loss,
      diarrhea, and colonic bleeding. Further histological examination of colons
      revealed healthy surface columnar epithelial cells free of erosion and ulceration
      compared with those without the drug treatment. At cellular level, the drug
      treatment decreased colon epithelial apoptosis, prevented goblet cell depletion,
      and promoted epithelial regeneration. AGN205203 may be unique among known EP4
      agonists for its metabolic and chemical stability, and it is amenable to systemic
      applications for the prevention and recovery of IBD.

PMID- 17008452
TI  - The effects of hyperthermia and hypoxia on ventilation during low-intensity
      steady-state exercise.
AB  - This study assessed whether the elevated sensitivity of ventilation to hypoxia
      during exercise is accounted for by an elevation of esophageal temperature
      (T(es)). Eleven males volunteered for two exercise sessions on an underwater,
      head-out cycle ergometer at a steady-state rate of oxygen consumption
      (V(.)(O(2))) of approximately 0.87 l/min (SD 0.07). In one exercise session, 31.5
      degrees C (SD 1.4) water held T(es) at a normothermic level of approximately 37.1
      degrees C, and in the other exercise session, water at 38.2 degrees C (SD 0.1)
      maintained a hyperthermic T(es) of approximately 38.5 degrees C. After a 30-min
      rest and 20-min warm-up, exercising participants inhaled air for 10 min [Euoxia 1
      (E1)], an isocapnic hypoxic gas mixture with 12% O(2) in N(2) (H1) for the next
      10 min and air again [Euoxia 2 (E2)] for the last 10 min. A significant increase
      in V(.)(E) during all hyperthermia conditions (0.01< P < 0.048) was evident;
      however, during hyperthermic hypoxia, there was a disproportionate and
      significant (P = 0.017) increase in V(.)(E) relative to normothermic hypoxia.
      This was the main explanation for a significant esophageal temperature and gas
      type interaction (P = 0.012) for V(.)(E). Significant effects of hyperthermia,
      isocapnic hypoxia, and their positive interaction remained evident after removing
      the influence of (V(.)(O(2))) on V(.)(E). Serum lactate and potassium
      concentrations, as well as hemoglobin oxygen saturation, were each not
      significantly different between normothermic and hyperthermic-hypoxic conditions.
      In conclusion, the elevated sensitivity of exercise ventilation to hypoxia during
      exertion appears to be modulated by elevations in esophageal temperature,
      potentially because of a temperature-mediated stimulation of the peripheral
      chemoreceptors.

PMID- 17008453
TI  - Thermoregulation: some concepts have changed. Functional architecture of the
      thermoregulatory system.
AB  - While summarizing the current understanding of how body temperature (T(b)) is
      regulated, this review discusses the recent progress in the following areas:
      central and peripheral thermosensitivity and temperature-activated transient
      receptor potential (TRP) channels; afferent neuronal pathways from peripheral
      thermosensors; and efferent thermoeffector pathways. It is proposed that
      activation of temperature-sensitive TRP channels is a mechanism of peripheral
      thermosensitivity. Special attention is paid to the functional architecture of
      the thermoregulatory system. The notion that deep T(b) is regulated by a unified
      system with a single controller is rejected. It is proposed that T(b) is
      regulated by independent thermoeffector loops, each having its own afferent and
      efferent branches. The activity of each thermoeffector is triggered by a unique
      combination of shell and core T(b)s. Temperature-dependent phase transitions in
      thermosensory neurons cause sequential activation of all neurons of the
      corresponding thermoeffector loop and eventually a thermoeffector response. No
      computation of an integrated T(b) or its comparison with an obvious or hidden set
      point of a unified system is necessary. Coordination between thermoeffectors is
      achieved through their common controlled variable, T(b). The described model
      incorporates Kobayashi's views, but Kobayashi's proposal to eliminate the term
      sensor is rejected. A case against the term set point is also made. Because this
      term is historically associated with a unified control system, it is more
      misleading than informative. The term balance point is proposed to designate the
      regulated level of T(b) and to attract attention to the multiple feedback,
      feedforward, and open-loop components that contribute to thermal balance.

PMID- 17008454
TI  - Atrophy-related ubiquitin ligases atrogin-1 and MuRF-1 are associated with
      uterine smooth muscle involution in the postpartum period.
AB  - The regulation of cell size depends on a delicate balance between protein
      synthesis and breakdown. Skeletal and cardiac muscle adapt to hormonal and
      neuronal stimuli and can rapidly hypertrophy and atrophy; however, the extent to
      which these processes occur in smooth muscle is less clear. Atrophy in striated
      muscle results from enhanced protein breakdown and is associated with a common
      transcriptional profile and activation of the ubiquitin-proteasome pathway,
      including induction of the muscle-specific ubiquitin protein ligases atrogin-1
      and muscle ring-finger protein 1 (MuRF-1). Here we show that atrogin-1 is also
      expressed in smooth muscle, and that both atrogin-1 and MuRF-1 are upregulated in
      the uterus following delivery, as rapid involution occurs. While these two genes
      are similarly induced in all types of muscle during rapid loss of cell mass,
      other striated muscle atrophy-specific transcriptional changes are not observed
      during uterine involution, suggesting different underlying molecular mechanisms.
      These results raise the possibility that activation of atrogin-1 and MuRF-1 may
      be a common general adaptation in cells undergoing a rapid reduction in size.

PMID- 17008455
TI  - Changes in mitochondrial electron transport chain activity during insect
      metamorphosis.
AB  - The midgut of the tobacco hornworm (Manduca sexta) is a highly aerobic tissue
      that is destroyed by programmed cell death during larval-pupal metamorphosis. The
      death of the epithelium begins after commitment to pupation, and the oxygen
      consumption of isolated midgut mitochondria decreases soon after commitment. To
      assess the role of the electron transport chain in this decline in mitochondrial
      function, the maximal activities of complexes I-IV of the respiratory chain were
      measured in isolated midgut mitochondria. Whereas there were no developmental
      changes in the activity of complex I or III, activities of complexes II and IV
      [cytochrome c oxidase (COX)] were higher in mitochondria from precommitment than
      postcommitment larvae. This finding is consistent with a higher rate of succinate
      oxidation in mitochondria isolated from precommitment larvae and reveals that the
      metamorphic decline in mitochondrial respiration is due to the targeted
      destruction or inactivation of specific sites within the mitochondria, rather
      than the indiscriminate destruction of the organelles. The COX turnover number (e
      x s(-1) x cytochrome aa3(-1)) was greater for the enzyme from precommitment than
      postcommitment larvae, indicating a change in the enzyme structure and/or its
      lipid environment during the early stages of metamorphosis. The turnover number
      of COX in the intact mitochondria (in organello COX) was also lower in
      postcommitment larvae. In addition to changes in the protein or membrane
      phospholipids, the metamorphic decline in this rate constant may be a result of
      the observed loss of endogenous cytochrome c.

PMID- 17008456
TI  - Myocardial preconditioning against ischemia-reperfusion injury is abolished in
      Zucker obese rats with insulin resistance.
AB  - Insulin resistance (IR) precedes the onset of Type 2 diabetes, but its impact on
      preconditioning against myocardial ischemia-reperfusion injury is unexplored. We
      examined the effects of diazoxide and ischemic preconditioning (IPC; 5-min
      ischemia and 5-min reperfusion) on ischemia (30 min)-reperfusion (240 min) injury
      in young IR Zucker obese (ZO) and lean (ZL) rats. ZO hearts developed larger
      infarcts than ZL hearts (infarct size: 57.3 +/- 3% in ZO vs. 39.2 +/- 3.2% in ZL;
      P < 0.05) and also failed to respond to cardioprotection by IPC or diazoxide
      (47.2 +/- 4.3% and 52.5 +/- 5.8%, respectively; P = not significant). In
      contrast, IPC and diazoxide treatment reduced the infarct size in ZL hearts (12.7
      +/- 2% and 16.3 +/- 6.7%, respectively; P < 0.05). The mitochondrial ATP
      activated potassium channel (K(ATP)) antagonist 5-hydroxydecanoic acid inhibited
      IPC and diazoxide-induced preconditioning in ZL hearts, whereas it had no effect
      on ZO hearts. Diazoxide elicited reduced depolarization of isolated mitochondria
      from ZO hearts compared with ZL (73 +/- 9% in ZL vs. 39 +/- 9% in ZO; P < 0.05).
      Diazoxide also failed to enhance superoxide generation in isolated mitochondria
      from ZO compared with ZL hearts. Electron micrographs of ZO hearts revealed a
      decreased number of mitochondria accompanied by swelling, disorganized cristae,
      and vacuolation. Immunoblots of mitochondrial protein showed a modest increase in
      manganese superoxide dismutase in ZO hearts. Thus obesity accompanied by IR is
      associated with the inability to precondition against ischemic cardiac injury,
      which is mediated by enhanced mitochondrial oxidative stress and impaired
      activation of mitochondrial K(ATP).

PMID- 17008457
TI  - Comparative shell buffering properties correlate with anoxia tolerance in
      freshwater turtles.
AB  - Freshwater turtles as a group are more resistant to anoxia than other
      vertebrates, but some species, such as painted turtles, for reasons not fully
      understood, can remain anoxic at winter temperatures far longer than others.
      Because buffering of lactic acid by the shell of the painted turtle is crucial to
      its long-term anoxic survival, we have tested the hypothesis that previously
      described differences in anoxia tolerance of five species of North American
      freshwater turtles may be explained at least in part by differences in their
      shell composition and buffering capacity. All species tested have large
      mineralized shells. Shell comparisons included 1) total shell CO2 concentration,
      2) volume of titrated acid required to hold incubating shell powder at pH 7.0 for
      3 h (an indication of buffer release from shell), and 3) lactate concentration of
      shell samples incubated to equilibrium in a standard lactate solution. For each
      measurement, the more anoxia-tolerant species (painted turtle, Chrysemys picta;
      snapping turtle, Chelydra serpentina) had higher values than the less anoxia
      tolerant species (musk turtle, Sternotherus odoratus; map turtle, Graptemys
      geographica; red-eared slider, Trachemys scripta). We suggest that greater
      concentrations of accessible CO2 (as carbonate or bicarbonate) in the more
      tolerant species enable these species, when acidotic, to release more buffer into
      the extracellular fluid and to take up more lactic acid into their shells. We
      conclude that the interspecific differences in shell composition and buffering
      can contribute to, but cannot explain fully, the variations observed in anoxia
      tolerance among freshwater turtles.

PMID- 17008458
TI  - Denervation does not change the ratio of collagen I and collagen III mRNA in the
      extracellular matrix of muscle.
AB  - Denervation or inactivity is known to decrease the mass and alter the phenotype
      of muscle and the mechanics of tendon. It has been proposed that a shift in the
      collagen of the extracellular matrix (ECM) of the muscle, increasing type III and
      decreasing type I collagen, may be partially responsible for the observed
      changes. We directly investigated this hypothesis using quantitative real-time
      PCR on muscles and tendons that had been denervated for 5 wk. Five weeks of
      denervation resulted in a 2.91-fold increase in collagen concentration but no
      change in the content of collagen in the muscle, whereas in the tendon there was
      no change in either the concentration or content of collagen. The expression of
      collagen I, collagen III, and lysyl oxidase mRNA in the ECM of muscle decreased
      (76 +/- 1.6%, 73 +/- 2.3%, and 83 +/- 3.2%, respectively) after 5 wk of
      denervation. Staining with picrosirius red confirmed the earlier observation of a
      change in staining color from red to green. Taken with the observed equivalent
      decreases in collagen I and III mRNA, this suggests that there was a change in
      orientation of the ECM of muscle becoming more aligned with the axis of the
      muscle fibers and no change in collagen type. The change in collagen orientation
      may serve to protect the smaller muscle fibers from damage by increasing the
      stiffness of the ECM and may partly explain why the region of the tendon closest
      to the muscle becomes stiffer after inactivity.

PMID- 17008459
TI  - Temperature acclimation modifies sinoatrial pacemaker mechanism of the rainbow
      trout heart.
AB  - The hypothesis of pacemaker level origin of thermal compensation in heart rate
      was tested by recording action potentials (AP) in intact sinoatrial tissue and
      enzymatically isolated pacemaker cells of rainbow trout acclimated at 4 degrees C
      (cold) and 18 degrees C (warm). With electrophysiological recordings, the primary
      pacemaker was located at the base of the sinoatrial valve, where a
      morphologically distinct ring of tissue comprising myocytes and neural elements
      was found by histological examination. Intrinsic beating rate of this pacemaker
      was higher in cold-acclimated (46 +/- 6 APs/min) than warm-acclimated trout (38
      +/- 3 APs/min; P < 0.05), and a similar difference was seen in beating rate of
      isolated pacemaker cells (44 +/- 6 vs. 38 +/- 6 APs/min; P < 0.05), supporting
      the hypothesis that thermal acclimation modifies the intrinsic pacemaker
      mechanism of fish heart. Inhibition of sarcoplasmic reticulum (SR) with 10 microM
      ryanodine and 1 microM thapsigargin did not affect heart rate in either warm- or
      cold-acclimated trout at 11 degrees C but reduced heart rate in warm-acclimated
      trout from 74 +/- 2 to 42 +/- 6 APs/min (P < 0.05) at 18 degrees C. At 11 degrees
      C, a half-maximal blockade of the delayed rectifier K+ current (I(Kr)) with 0.1
      microM E-4031 reduced heart rate more in warm-acclimated (from 45 +/- 1 to 24 +/-
      5 APs/min) than cold-acclimated trout (56 +/- 3 vs. 48 +/- 2 APs/min), whereas
      I(Kr) density was higher and AP duration less in cold-acclimated trout (P >
      0.05). Collectively, these findings suggest that a cold-induced increase in AP
      discharge frequency is at least partly due to higher density of the I(Kr) in the
      cold-acclimated trout, whereas contribution of SR Ca2+ release to thermal
      compensation of heart rate is negligible.

PMID- 17008460
TI  - Sex-based differences in myocardial contractile reserve.
AB  - Recent studies have identified sex differences in heart function that may affect
      the risk of developing heart failure. We hypothesized that there are fundamental
      differences in calcium (Ca) regulation in cardiac myocytes of males and
      premenopausal females. Isometric force transients (n = 45) were measured at
      various stimulation frequencies to define the force frequency responses (FFR)
      (0.5, 1.0, 1.5, and 2.0 Hz) during either changes in bath Ca ([Ca]o) (1.0, 1.75,
      3.5, and 7.0 mM) or length-tension (20, 40, 60, 80, and 100% L(max)) in right
      ventricle trabeculae from normal male (MT) and premenopausal female (FT) cats.
      Force-Ca measurements were also obtained in chemically skinned trabeculae. Under
      basal conditions (0.5 Hz, 1.75 mM Ca, 80% L(max)) both MT and FT achieved similar
      developed forces (DF) (MT 11 +/- 1, FT = 10 +/- 1 mN/mm2). At low rates and
      lengths, there is no sex difference. At higher preloads and rates, there is a
      separation in DF in MT and FT. At basal [Ca]o both MT and FT exhibited positive
      FFR (2.0 Hz, 1.75 mM Ca: MT 38 +/- 3, FT 21 +/- 4 mN/mm2); however, at higher
      [Ca]o, MT achieved greater DF (2.0 Hz, 7.0 mM Ca: MT 40 +/- 3 and FT = 24 +/- 4
      mN/mm2). We detected no sex difference in myofilament Ca sensitivity at a
      sarcomere length of 2.1 mum. However, rapid cooling contractures indicated
      greater sarcoplasmic reticulum (SR) Ca load in MT at higher frequencies. Despite
      virtually identical contractile performance under basal conditions, significant
      sex differences emerge under conditions of increased physiological stress. Given
      the lack of sex differences in myofilament Ca sensitivity, these studies suggest
      fundamental sex differences in cellular Ca regulation to achieve contractile
      reserve, with myocardium from males exhibiting higher SR Ca load.

PMID- 17008461
TI  - Estrogen deficiency decreases ischemic tolerance in the aged rat heart: Roles of
      PKCdelta, PKCepsilon, Akt, and GSK3beta.
AB  - The mechanisms underlying the age-dependent reversal of female cardioprotection
      are poorly understood and complicated by findings that estrogen replacement is
      ineffective at reducing cardiovascular mortality in postmenopausal women.
      Although several protective signals have been identified in young animals,
      including PKC and Akt, how these signals are affected by age, estrogen
      deficiency, and ischemia-reperfusion (I/R) remains unknown. To determine the
      independent and combined effects of age and estrogen deficiency on I/R injury and
      downstream PKC-Akt signaling, adult and aged female F344 rats (n = 12/age) with
      ovaries intact or ovariectomy (Ovx) were subjected to I/R using Langendorff
      perfusion (31-min global-ischemia). Changes in cytosolic (s), nuclear (n),
      mitochondrial (m) PKC (delta, epsilon) levels, and changes in total Akt and mGSK
      3beta phosphorylation after I/R were assessed by Western blot analysis.
      Senescence increased infarct size 50% in ovary-intact females (P < 0.05), whereas
      no differences in LV functional recovery or estradiol levels were observed. Ovx
      reduced functional recovery to a greater extent in aged compared with adult rats
      (P < 0.05). In aged (vs. adult), levels of m- and nPKC(-delta, -epsilon) were
      markedly decreased, whereas mGSK3beta levels were increased (P < 0.05). Ovx led
      to greater levels of sPKC(-delta, -epsilon) independent of age (P < 0.05). I/R
      reduced p-Akt(Ser473) levels by 57% and increased mGSK-3beta accumulation 1.77
      fold (P < 0.05) in aged, ovary-intact females. These data suggest, for the first
      time, that estrogen alone cannot protect the aged female myocardium from I/R
      damage and that age- and estrogen-dependent alterations in PKC, Akt, and GSK
      3beta signaling may contribute to loss of ischemic tolerance.

PMID- 17008462
TI  - Expression and localization of monocarboxylate transporters and sodium/proton
      exchangers in bovine rumen epithelium.
AB  - Monocarboxylate-H+ cotransporters, such as monocarboxylate transporter (MCT)
      SLC16A, have been suggested to mediate transruminal fluxes of short-chain fatty
      acids, ketone bodies, and lactate. Using an RT-PCR approach, we demonstrate
      expression of MCT1 (SLC16A1) and MCT2 (SLC16A7) mRNA in isolated bovine rumen
      epithelium. cDNA sequence from these PCR products combined with overlapping
      expressed sequence tag data allowed compilation of the complete open reading
      frames for MCT1 and MCT2. Immunohistochemical localization of MCT1 shows plasma
      membrane staining in cells of the stratum basale, with intense staining of the
      basal aspects of the cells. Immunostaining decreased in the cell layers toward
      the rumen lumen, with weak staining in the stratum spinsoum. Immunostaining in
      the stratum granulosum and stratum corneum was essentially negative. Since
      monocarboxylate transport will load the cytosol with acid, expression and
      location of Na+/H+ exchanger (NHE) family members within the rumen epithelium
      were determined. RT-PCR demonstrates expression of multiple NHE family members,
      including NHE1, NHE2, NHE3, and NHE8. In contrast to MCT1, immunostaining showed
      that NHE1 was predominantly localized to the stratum granulosum, with a
      progressive decrease toward the stratum basale. NHE2 immunostaining was observed
      mainly at an intracellular location in the stratum basale, stratum spinosum, and
      stratum granulosum. Given the anatomic localization of MCT1, NHE1, and NHE2, the
      mechanism of transruminal short-chain fatty acid, ketone body, and lactate
      transfer is discussed in relation to a functional model of the rumen epithelium
      comprising an apical permeability barrier at the stratum granulosum, with a cell
      syncitium linking the stratum granulosum to the blood-facing stratum basale.

PMID- 17008463
TI  - The impact of hypoxia on in vivo glucose uptake in a hypoglycemic fish,
      Myoxocephalus scorpius.
AB  - The mechanisms controlling carbohydrate utilization in teleost fish are poorly
      understood, particularly in the heart. Tissue glucose uptake and cardiovascular
      characteristics were measured in the short-horned sculpin, Myoxocephalus
      scorpius, a species exhibiting low blood glucose levels, during normoxia and
      hypoxia to assess the role of adenosine receptors in the control of glucose
      uptake and anaerobic metabolism. As expected, hypoxia exposure (300 min at 2 mg/l
      dissolved oxygen) resulted in a bradycardia and plasma lactate accumulation, but
      glucose uptake rates did not change in heart, brain, gill, spleen, and white
      muscle. Plasma glucose-to-intracellular glucose ratios indicated that glucose
      uptake was the rate-limiting step in glucose utilization. The majority of
      intracellular glucose was unphosphorylated, however, suggesting that hexokinase
      is also important in controlling the tissue glucose gradient. During hypoxia, the
      cholinergic blocker atropine resulted in tachycardia but did not significantly
      change tissue glucose uptake rates or heart and brain adenosine levels. In
      contrast, the combined treatment of atropine and an adenosine receptor blocker [8
      (p-sulfophenyl)theophylline] during hypoxia increased heart glucose uptake to
      levels fivefold higher than normoxic fish, with no additive effects on
      cardiovascular parameters. Significant tissue lactate accumulation was observed
      in this group of fish, signifying that adenosine receptors may depress anaerobic
      metabolism, even though tissue adenosine accumulation was absent during hypoxia.
      White muscle accumulated glucose during normoxia, suggesting the presence of
      gluconeogenic pathways or active uptake mechanisms not previously described in
      this tissue.

PMID- 17008464
TI  - Estrogen effects on fetal and neonatal testicular development.
AB  - In recent years, evidences have accumulated that exposure to environmental
      components with estrogenic activity causes reproductive disorders in human
      populations. Studies conducted over the past 50 years have clearly shown a
      continual decline in semen quality accompanied by an increase in male
      reproductive disorders during this period in industrial countries. As healthy
      gametes are a prerequisite for healthy children, such disorders are a significant
      problem not only for the current society, but also for future generations. These
      male reproductive disorders have been attributed to xenobiotics, and particularly
      to xenoestrogens, which have steadily increased in diversity and concentration in
      the environment and food. Epidemiological, clinical, and experimental studies
      have suggested that excessive exposure to estrogens and xenoestrogens during
      fetal and neonatal development may induce testicular developmental disorders,
      leading to alterations in the adult male fertility. Recently, we have clearly
      demonstrated that fetal and neonatal testes are very sensitive to estrogens, as
      the inactivation of estrogen receptor alpha increases steroidogenesis and the
      inactivation of estrogen receptor beta enhances development of the germ cell
      lineage in the male.

PMID- 17008465
TI  - Prenatal programming of the female reproductive neuroendocrine system by
      androgens.
AB  - It has been clear for several decades that the areas of the brain that control
      reproductive function are sexually dimorphic and that the 'programming actions'
      of the male gonadal steroids are responsible for sex-specific release of the
      gonadotrophins from the pituitary gland. The administration of exogenous steroids
      to fetal/neonatal animals has pinpointed windows of time in an animals'
      development when the reproductive neuroendocrine axis is responsive to the
      organisational influences of androgens. These 'critical' periods for sexual
      differentiation of the brain are trait- and species-specific. The neural network
      regulating the activity of the gonadotrophin releasing hormone (GnRH) neurones is
      vital to the control of reproductive function. It appears that early exposure to
      androgens does not influence the migratory pathway of the GnRH neurone from the
      olfactory placode or the size of the population of neurones that colonise the
      postnatal hypothalamus. However, androgens do influence the number and the nature
      of connections that these neurones make with other neural phenotypes. Gonadal
      steroid hormones play key roles in the regulation of GnRH release acting largely
      via steroid-sensitive intermediary neurones that impinge on the GnRH cells.
      Certain populations of hormonally responsive neurones have been identified that
      are sexually dimorphic and project from hypothalamic areas known to be involved
      in the regulation of GnRH release. These neurones are excellent candidates for
      the programming actions of male hormones in the reproductive neuroendocrine axis
      of the developing female.

PMID- 17008466
TI  - Abilities of cumulus and granulosa cells to enhance the developmental competence
      of bovine oocytes during in vitro maturation period are promoted by midkine; a
      possible implication of its apoptosis suppressing effects.
AB  - We previously reported that when midkine (MK), a heparin-binding growth
      differentiation factor was used in in vitro maturation (IVM) culture of bovine
      cumulus-enclosed oocytes (CEOs), their developmental competence to the blastocyst
      stage after in vitro fertilization (IVF) was enhanced and the effect of MK might
      be mediated by its action upon mural granulosa cells and cumulus cells that
      closely surround the oocyte. In the present study, when denuded oocytes (DOs)
      were matured in IVM medium with or without MK (200 ng/ml) in the presence or
      absence of isolated cumulus cell masses and subjected to IVF, the enhancing
      effects of MK on the developmental competence of DOs to the blastocyst stage
      after IVF were exerted only in the presence of cumulus cells. In addition, we
      prepared the conditioned media of granulosa cells cultured with or without 200 ng
      MK/ml (CMMK+ or CMMK- respectively) and examined their effects on the IVM of DOs
      in terms of their developmental competence to the blastocyst stage after IVF. The
      supplementation of CMMK+ into IVM medium at 40% (v/v) significantly enhanced the
      blastocyst development compared with the no additive control and the CMMK-
      supplemented groups. Furthermore, the effects of MK during IVM of bovine CEOs on
      the cumulus cell apoptosis were investigated. CEOs were cultured up to 24 h in
      IVM medium without (control) or with 200 ng MK/ml. The genomic DNA was extracted
      from CEOs at 0, 6, 12, 18 and 24 h of IVM and subjected to ligation-mediated PCR
      (LM-PCR) to detect the apoptotic internucleosomal DNA fragmentation. DNA
      fragmentation was scarcely detected at the start of IVM, whereas it increased
      time-dependently as the IVM culture progressed. The degree of the fragmentation
      was significantly lower in the MK-treatment group compared with the control group
      at 18 and 24 h of IVM. The apoptosis-suppressing effect of MK on cumulus cells
      was further confirmed in situ by using TUNEL on CEOs. In conclusion, data from
      the present study further confirmed that MK enhances the developmental competence
      of bovine oocytes via cumulus and granulosa cells. It was also demonstrated that
      MK suppresses the apoptosis that occurs in cumulus cells during the period of IVM
      of bovine CEOs. The putative soluble factor(s) from cumulus cells was suggested
      from the experiment using CMMK+ . MK may promote the production of such factors
      in part by its anti-apoptotic effects on cumulus cells.

PMID- 17008467
TI  - Diploid porcine parthenotes produced by inhibition of first polar body extrusion
      during in vitro maturation of follicular oocytes.
AB  - We investigated nuclear progression and in vitro embryonic development after
      parthenogenetic activation of porcine oocytes exposed to cytochalasin B (CB)
      during in vitro maturation (IVM). Nuclear progression was similar in control
      oocytes and oocytes matured in the presence of 1 microg/ml CB (IVM-CB group) by
      37 h IVM; at this time the proportion of oocytes that had reached or passed
      through the anaphase-I stage did not differ significantly between the IVM-CB and
      the control groups (61.3 and 69.9% respectively; P < 0.05). After IVM for 37 h,
      no polar body extrusion was observed in the IVM-CB group. In these oocytes, the
      two lumps of homologous chromosomes remained in the ooplasm after their
      segregation and turned into two irregular sets of condensed chromosomes. By 41 h
      IVM, the double sets of chromosomes had reunited in 89.5% IVM-CB oocytes and
      formed a single large metaphase plate, whereas 68.8% of the control oocytes had
      reached the metaphase-II stage by this time. When IVM-CB oocytes cultured for 46
      h were stimulated with an electrical pulse and subsequently cultured for 8 h
      without CB, 39.0% of them extruded a polar body and 82.9% of them had a female
      pronucleus. Chromosome analysis revealed that the majority of oocytes that
      extruded a polar body were diploid in both the control and the IVM-CB groups.
      However, the incidence of polyploidy in the IVM-CB group was higher than that in
      the control group (P < 0.05). In vitro development of diploid parthenotes in the
      control and the IVM-CB groups was similar in terms of blastocyst formation rates
      (45.8 and 42.8% respectively), number of blastomeres (39.9 and 44.4
      respectively), the percentage of dead cells (4.3 and 2.9% respectively), and the
      frequency of apoptotic cells (7.3 and 6.3% respectively). Tetraploid embryos had
      a lower blastocyst formation rate (25.5%) and number of cells (26.2); however,
      the proportion of apoptotic nuclei (7.0%) was similar to that in diploid
      parthenotes. These results suggest that the proportion of homozygous and
      heterozygous genes does not affect in vitro embryo development to the blastocyst
      stage.

PMID- 17008468
TI  - Effects of selective inhibition of cyclooxygenase and lipooxygenase pathways in
      follicle rupture and ovulation in the rat.
AB  - Treatment with non-steroidal anti-inflammatory drugs, either non-selective or
      selective cyclooxygenase-2 (COX-2) inhibitors, consistently impairs ovulation,
      indicating the essential role of COX-2/prostaglandins in the ovulatory process.
      Indomethacin, a potent inhibitor of both COX-1 and COX-2, induced several
      ovulatory alterations, consisting of a decrease in the number of oocytes
      effectively ovulated, trapping of oocytes inside the luteinized follicle, as well
      as abnormal follicle rupture at the basolateral sides, with release of the oocyte
      and follicular fluid to the interstitium. Yet, the precise role of prostaglandins
      in ovulation and whether some of the ovulatory defects induced by indomethacin
      are due to interference with additional components of the ovulatory cascade,
      beyond prostaglandin synthesis, are not completely understood. We have used
      gonadotrophin-primed immature rats to analyse whether, compared to indomethacin,
      selective inhibition of COX-2, with or without concomitant inhibition of COX-1,
      or selective inhibition of the lipooxygenase (LOX) pathway, induce similar
      ovulatory alterations. Immature rats (27 days of age) were injected PMSG (10 IU),
      and 48 h later hCG (10 IU) subcutaneously, and different anti-inflammatory drugs.
      Animals were killed at 21 h after hCG injection. Rats treated with the selective
      COX-2 inhibitor NS398 (10 mg/kg body weight, (bw)) showed alterations in follicle
      rupture as those treated with indomethacin (0.5 mg/rat), albeit affecting a lower
      number of follicles, irrespective of the concomitant inhibition of COX-1 with the
      selective inhibitor SC560 (10 mg/kg bw). Rats treated with the LOX inhibitor NDGA
      (300 mg/kg bw) did not show ovulatory alterations. These data indicate that the
      characteristic alterations of follicle rupture induced by indomethacin, are also
      induced by selective COX-2 inhibitors, strengthening the contention that
      prostaglandins play a crucial role in the spatial targeting of follicle rupture
      at the apex.

PMID- 17008469
TI  - Expression of endothelial nitric oxide synthase in the ovine ovary throughout the
      estrous cycle.
AB  - This study was conducted to evaluate the expression of endothelial nitric oxide
      synthase (eNOS) in ovarian follicles and corpora lutea (CL) throughout the
      estrous cycle in sheep. Three experiments were conducted to (1) immunolocalize
      eNOS protein, (2) determine expression of mRNA for eNOS and its receptor
      guanylate cyclase 1 soluble beta3 (GUCY1B3), and (3) co-localize eNOS and
      vascular endothelial growth factor (VEGF) proteins in the follicles and/or CL
      throughout the estrous cycle. In experiment 1, ovaries were collected from ewes
      treated with FSH, to induce follicular growth or atresia. In experiment 2,
      ovaries were collected from ewes treated with FSH and hCG to induce follicular
      growth and ovulation. In experiment 3, ovaries were collected from superovulated
      ewes to generate multiple CL on days 2, 4, 10, and 15 of the estrous cycle. In
      experiments 1 and 2, the expression of eNOS protein was detected in the blood
      vessels of the theca externa and interna of healthy ovarian follicles. However,
      in early and advanced atretic follicles, eNOS protein expression was absent or
      reduced. During the immediate postovulatory period, eNOS protein expression was
      detected in thecal-derived cells that appeared to be invading the granulosa
      layer. Expression of eNOS mRNA tended to increase in granulosa cells at 12 and 24
      h, and in theca cells 48 h after hCG injection. In experiment 3, eNOS protein was
      located in the blood vessels of the CL during the estrous cycle. Dual
      localization of eNOS and VEGF proteins in the CL demonstrated that both were
      found in the blood vessels.

PMID- 17008470
TI  - Administration of vascular endothelial growth factor Trap during the 'post
      angiogenic' period of the luteal phase causes rapid functional luteolysis and
      selective endothelial cell death in the marmoset.
AB  - The intense angiogenesis characteristic of early corpus luteum development is
      dependent upon vascular endothelial growth factor (VEGF) as inhibitors of VEGF
      administered at the peri-ovulatory period suppress endothelial cell proliferation
      and progesterone secretion. We now report that administration of VEGF Trap, a
      soluble decoy receptor-based inhibitor, at the mid- or the late luteal phase in
      the marmoset results in a rapid decline in plasma progesterone. Since
      vascularisation of the corpus luteum is largely complete by the mid-luteal phase,
      it suggested that this functional luteolysis involved mechanisms other than
      inhibition of angiogenesis. A second experiment investigated the role of VEGF in
      maintaining the integrity of the luteal vasculature and hormone-producing cells.
      VEGF Trap was administered to marmosets in the mid-luteal phase and ovaries were
      obtained 1, 2, 4 or 8 days later for localisation of activated caspase-3 staining
      in the corpus luteum and compared with those obtained 2, 4 and 8 days after
      administration of control protein. The number of cells with activated caspase-3
      staining was significantly increased after administration of VEGF Trap. Dual
      staining of activated caspase-3 with the endothelial cell marker CD31 showed that
      at 1 day post-treatment, more than 90% caspase-3-stained cells were vascular
      endothelium, prior to detection of an increasing incidence in death of hormone
      producing cells on days 2 and 4. Staining with CD31 showed that the endothelial
      cell area was decreased after treatment. By 8 days after treatment, corpora lutea
      had regressed to varying degrees, while all control corpora lutea remained
      healthy. These results show that VEGF inhibition in the mid- or the late luteal
      phase induces functional luteolysis in the marmoset that is associated with
      premature and selective death of endothelial cells.

PMID- 17008471
TI  - Spermatogenesis does not require the local production of follistatin.
AB  - It has been proposed that follistatin can modulate the actions of activins and/or
      other members of the transforming growth factor-beta superfamily of proteins on
      testicular function, since mice overexpressing follistatin showed spermatogenic
      disruption. However, since mice with targeted disruption of the follistatin gene
      die soon after birth, it is not feasible to determine the effect of the absence
      of follistatin on testicular function using this model. To further understand the
      role of follistatin on the development and maintenance of spermatogenesis, fetal
      testes, collected by Caesarean section at day 18 of gestation from follistatin
      null mice, were transplanted to the external ear of castrated recombination
      activating gene 1 immunocompromised male mice. The testicular grafts were then
      analysed 7-8 weeks after transplantation and showed that full spermatogenesis
      developed in both the testes of wild-type and follistatin null mice. This study
      indicates that, if follistatin is required to modulate spermatogenic development,
      it is not supplied by local testicular production but by circulating follistatin
      from the host mouse.

PMID- 17008472
TI  - Leydig cell function in mice lacking connexin43.
AB  - Connexin43 (Cx43) is the most abundantly expressed member of the connexin (gap
      junction protein) family and the only one so far identified in mouse Leydig cell
      gap junctions. Mice lacking Cx43 were used to investigate its role in testicular
      androgen production and regulation. Testes from term fetuses were grafted under
      the kidney capsules of castrated adult males. After 3 weeks, serum from host mice
      was analyzed for androgens. In order to test their response to stimulation, the
      grafted testes were incubated in vitro with varying concentrations of LH and
      their androgen end products analyzed. Incubation with radiolabeled progesterone
      was followed by high performance liquid chromatography to quantify the androgen
      intermediate metabolites. Radiolabeled testosterone in the presence of NADPH was
      used to determine the activity of testosterone-metabolizing enzymes 17beta
      hydroxysteroid dehydrogenase (17betaHSD), 5alpha-reductase (5alphaR), and 3alpha
      hydroxysteroid dehydrogenase (3alpha HSD). Serum androgen levels did not differ
      between hosts carrying wild-type versus null mutant grafts although Cx43
      deficient testes had more 17betaHSD and 5alphaR activity than wild-type controls.
      Furthermore, the genotype of grafted testes did not influence LH-stimulated
      androgen production in vitro. These results indicate that the steroidogenic
      function of Leydig cells is not compromised by the absence of Cx43, perhaps
      because other gap junction proteins are present. Dye transfer experiments
      demonstrated that Cx43-deficient Leydig cells retain intercellular coupling,
      indicating that Cx43 is not the only protein contributing to their gap junctions.
      Thus, despite their prominence in Leydig cells, Cx43 gap junctions are not
      essential for androgen production.

PMID- 17008473
TI  - Successful transplantation of bovine testicular cells to heterologous recipients.
AB  - While heterologous germ cell transplantation was successful in pigs and goats,
      autologous transplantation alone has been reported to result in donor-derived
      spermatogenesis in cattle. The objective of this study was to investigate whether
      the transplantation of heterologous germ cells could result in colonization of
      recipient testes in cattle of different breeds. Testicular cells were isolated
      from 8 Bos taurus donor bull calves and then transferred into 15 Bos indicus
      cross bull calves. All animals were prepubertal, donors were aged 5-7 months and
      recipients 5-11 months, and scrotal circumferences ranged from 15 to 22 cm.
      Single cell suspensions of donor testicular cells, prepared by enzymatic
      digestion, were labelled with fluorescent dyes PKH26 or CFDA-SE, before transfer
      into the rete testis of recipients under ultrasonographic guidance. To assess the
      longevity of colonization by donor cells, recipients were castrated 2-30 weeks
      after cell transfer. Donor cells were observed in 15/25 (60%) of the testes that
      received PKH26-labelled cells, whereas no CFDA-SE-positive cell was identified in
      any recipients. The maturity of the donors or recipients (measured by scrotal
      circumference) did not affect colonization potential. In freshly isolated
      tubules, clumps of PKH26-positive cells were observed, which indicated either
      cell division or extensive local colonization of specific areas of the tubules.
      In frozen sections, PKH26-positive cells were identified on the seminiferous
      tubule basement membrane, which indicated that these cells had successfully
      migrated from the tubule lumen and were likely to be spermatogonia. We conclude
      that PKH26 was more suitable for labelling donor testis cells and donor cells can
      be identified up to 6 months following transfer. These results indicate that
      allogeneic transplantation of testicular cells can occur between Bos taurus and
      Bos indicus cattle. Further studies will investigate functionality of transferred
      testicular cells.

PMID- 17008474
TI  - Expression of stathmin in human uterus and decidualizing endometrial stromal
      cells.
AB  - The cytosolic phosphoprotein stathmin is upregulated at the site of embryo
      implantation in the rodents. However, stathmin expression in the human uterus has
      not yet been investigated. The distribution of uterine and placental stathmin was
      analyzed by immunohistochemistry, while stathmin mRNA expression was detected in
      endometrial tissues by the reverse transcriptase-PCR. Cultured endometrial
      stromal cells were used to investigate whether stathmin plays a role in
      decidualization. Stathmin is expressed specifically in the glandular epithelium
      and the stromal cells of human endometrial tissue. It is also expressed by
      cytotrophoblasts and extravillous trophoblasts, but not by syncytiotrophoblasts
      or decidual tissues during the first trimester of pregnancy. When stromal cells
      isolated from normal endometrial tissues were cultured and stimulated to
      decidualize by progesterone (P4) plus estrogen or dibutyryl cyclic 3',5'-AMP,
      their total and phosphorylated stathmin levels decreased. Knocking down stathmin
      expression in the cultured stromal cells using small interfering RNA, before the
      cells were exposed to the decidualizing agents, significantly suppressed
      decidualization, as indicated by the decreased expression of IGF-binding protein
      1 and prolactin. Stathmin is differently expressed in human endometrial and
      placental cells and may participate in the decidualization of endometrial stromal
      cells.

PMID- 17008475
TI  - A bovine oviduct epithelial cell suspension culture system suitable for studying
      embryo-maternal interactions: morphological and functional characterization.
AB  - We established a short-term (24 h) culture system for bovine oviduct epithelial
      cells (BOECs), obtained on day 3.5 of the estrous cycle and evaluated the cells
      with respect to morphological criteria, marker gene expression, and hormone
      responsiveness. BOEC sheets were isolated mechanically from the ampulla with
      similar yields from oviducts ipsi- and contralateral to the ovulation site (57.9
      +/- 4.6 and 56.4 +/- 8.0 x 10(6) cells). BOECs showed > 95% purity and cells
      cultured for 24 h maintained morphological characteristics present in vivo, as
      determined by light microscopy, scanning electron microscopy, and transmission
      electron microscopy. Both secretory cells with numerous secretory granules and
      ciliated cells with long, well-developed, and vigorously beating kinocilia were
      visible. Quantitative real-time PCR failed to detect significant differences in
      transcript levels between ipsi-and contralateral BOECs for the majority of marker
      genes (estrogen receptors alpha and beta (ESR1 and ESR2), 3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMGCR), oviductal glycoprotein 1 (OVGP1),
      progesterone receptor (PGR), and tumor rejection antigen 1 (TRA1)) throughout the
      24 h culture period. However, the combined data of all time points for
      glutathione peroxidase 4 (GPX4), a gene previously shown to be expressed at
      higher levels in the ipsilateral oviduct in vivo, also indicated significantly
      different mRNA levels in vitro. The expression of marker genes remained stable
      after 6 h cell culture, indicating only a short adaptation period. Western blot
      analysis confirmed ESR1 and PGR protein expression throughout the culture period.
      In agreement with cyclic differences in vivo, estradiol-17beta stimulation
      increased PGR transcript abundance in BOECs. Our novel culture system provides
      functional BOECs in sufficient quantities for holistic transcriptome and proteome
      studies, e.g. for deciphering early embryo-maternal communication.

PMID- 17008476
TI  - Endocrine differentiation of fetal ovaries and testes of the spotted hyena
      (Crocuta crocuta): timing of androgen-independent versus androgen-driven genital
      development.
AB  - Female spotted hyenas (Crocuta crocuta) have an erectile peniform clitoris and a
      pseudoscrotum but no external vagina, all established by day 35 of a 110-day
      gestation. Recent studies indicate that these events are androgen-independent,
      although androgen secretion by fetal ovaries and testis was hypothesized
      previously to induce phallic development in both sexes. We present the first data
      relating to the capacity of the ovaries and testes of the spotted hyena to
      synthesize androgens at different stages of fetal life. Specifically, spotted
      hyena fetal gonads were examined by immunohistochemistry at GD 30, 45, 48, 65,
      and 95 for androgen-synthesizing enzymes, as related to the morphological
      development. Enzymes included 17alpha-hydroxylase/17,20-lyase cytochrome P450
      (P450c17), cytochrome b5, 3beta-hydroxysteroid dehydrogenase (3betaHSD), and
      cholesterol side-chain cleavage cytochrome P450 (P450scc). Anti-Mullerian-hormone
      (AMH) expression was also examined. AMH was strongly expressed in fetal Sertoli
      cells from GD 30 and after. P450c17 expression was detected in Leydig cells of
      developing testes and surprisingly in Mullerian duct epithelium. Fetal ovaries
      began to organize and differentiate by GD 45, and medullary cells expressed
      P450c17, cytochrome b5, 3betaHSD, and P450scc. The findings support the
      hypothesis that external genital morphology is probably androgen-independent
      initially, but that fetal testicular androgens modify the secondary, male
      specific phallic form and accessory organs. Fetal ovaries appear to develop
      substantial androgen-synthesizing capacity but not until phallic differentiation
      is complete, i.e. after GD 45 based on circulating androstenedione
      concentrations. During late gestation, fetal ovaries and testes synthesize
      androgens, possibly organizing the neural substrates of aggressive behaviors
      observed at birth in spotted hyenas. These data provide an endocrine rationale
      for sexual dimorphisms in phallic structure and reveal a potential source of
      androgenic support for neonatal aggression in female and male C. crocuta.

PMID- 17008477
TI  - Phodopus campbelli detect reduced photoperiod during development but, unlike
      Phodopus sungorus, retain functional reproductive physiology.
AB  - Golden (Mesocricetus auratus) and Siberian (Phodopus sungorus) hamsters are
      widely used as animal models for seasonal reproduction; but M. auratus shows no
      developmental delay in short days until after sexual maturity, whereas P.
      sungorus juveniles delay development in short days. As the photoperiodic response
      of Phodopus campbelli is not well established, litters of the two Phodopus
      species were gestated and reared under long days (14 h light:10 h darkness) or
      short days (10 h light:14 h darkness) until 70 days of age. As expected, under
      short photoperiod P. sungorus showed reduced body, testes, epididymides, uterus,
      and ovary weight; antral follicles and corpora lutea were absent and vaginae
      remained closed. Animals moulted to winter pelage, and low concentrations of each
      of leptin, testosterone, and prolactin were present in male serum. Phodopus
      campbelli juveniles also responded to the short photoperiod as measured by
      reduced body, testes, epididymides, and ovary weight. The summer pelage
      persisted. However, both sexes of P. campbelli developed functional reproduction
      under 10 h light:14 h darkness. All females had a patent vagina by 10 weeks;
      ovaries contained antral follicles and corpora lutea, and uteri were not reduced
      in weight. In males, the concentrations of testosterone, leptin, and prolactin
      were not reduced by short photoperiod. Developmental patterns in the three
      species of hamster, therefore, differ and are not predicted by relatedness or
      latitude of origin. Other ecological traits, such as predictability of summer
      rainfall, ambient temperature, and differential responses to social cues might be
      important.

PMID- 17008478
TI  - Caring for the burden of COPD.

PMID- 17008479
TI  - Anger, stress, dysregulation produces wear and tear on the lung.

PMID- 17008480
TI  - Spirometric screening: Does it work?

PMID- 17008481
TI  - IL-10: Another therapeutic target in idiopathic pulmonary fibrosis?

PMID- 17008483
TI  - Mesothelioma after lung transplantation.
AB  - The case history is presented of a lung transplant recipient who developed
      malignant mesothelioma. This is thought to be the first such report. Mesothelioma
      should be suspected in lung transplant recipients with a haemorrhagic pleural
      effusion in the native lung when there is no convincing evidence for bronchogenic
      carcinoma or post transplant lymphoproliferative disease, even in the absence of
      exposure to asbestos.

PMID- 17008482
TI  - Asthma exacerbations . 3: Pathogenesis.
AB  - Asthma exacerbations are an exaggerated lower airway response to an environmental
      exposure. Respiratory virus infection is the most common environmental exposure
      to cause a severe asthma exacerbation. Airway inflammation is a key part of the
      lower airway response in asthma exacerbation, and occurs together with airflow
      obstruction and increased airway responsiveness. The patterns of airway
      inflammation differ according to the trigger factor responsible for the
      exacerbation. The reasons for the exaggerated response of asthmatic airways are
      not completely understood, but recent studies have identified a deficient
      epithelial type 1 interferon response as an important susceptibility mechanism
      for viral infection.

PMID- 17008485
TI  - Whole blood IFN-gamma assay for detecting TB in children.

PMID- 17008486
TI  - Heme oxygenase-1 gene promoter polymorphism and decline in lung function in
      Japanese men.

PMID- 17008487
TI  - Cerebral tuberculoma.

PMID- 17008488
TI  - Localized temporal change of the Earth's inner core boundary.
AB  - Compressional waves of an earthquake doublet (two events occurring in the South
      Sandwich Islands on 1 December 1993 and 6 September 2003), recorded at three
      seismic stations in Russia and Kyrgyzstan and reflected off Earth's inner core
      boundary, arrived at least from 39 to 70 milliseconds earlier in the 2003 event
      than in the 1993 event. Such changes indicate that Earth's inner core radius
      enlarged locally beneath middle Africa by 0.98 to 1.75 kilometers between the
      times of these two events. Changes of the inner core radius may be explained by
      either a differential motion of the inner core, assuming that irregularities are
      present at the inner core boundary and fixed to the inner core, or a rapid growth
      of the inner core by this amount.

PMID- 17008489
TI  - Correcting quantum errors with entanglement.
AB  - We show how entanglement shared between encoder and decoder can simplify the
      theory of quantum error correction. The entanglement-assisted quantum codes we
      describe do not require the dual-containing constraint necessary for standard
      quantum error-correcting codes, thus allowing us to "quantize" all of classical
      linear coding theory. In particular, efficient modern classical codes that attain
      the Shannon capacity can be made into entanglement-assisted quantum codes
      attaining the hashing bound (closely related to the quantum capacity). For
      systems without large amounts of shared entanglement, these codes can also be
      used as catalytic codes, in which a small amount of initial entanglement enables
      quantum communication.

PMID- 17008490
TI  - Anatomy of a flaring proto-planetary disk around a young intermediate-mass star.
AB  - Although planets are being discovered around stars more massive than the Sun,
      information about the proto-planetary disks where such planets have built up is
      sparse. We have imaged mid-infrared emission from polycyclic aromatic
      hydrocarbons at the surface of the disk surrounding the young intermediate-mass
      star HD 97048 and characterized the disk. The disk is in an early stage of
      evolution, as indicated by its large content of dust and its hydrostatic flared
      geometry, indicative of the presence of a large amount of gas that is well mixed
      with dust and gravitationally stable. The disk is a precursor of debris disks
      found around more-evolved A stars such as beta-Pictoris and provides the rare
      opportunity to witness the conditions prevailing before (or during) planet
      formation.

PMID- 17008491
TI  - Genetic testing oversight.

PMID- 17008492
TI  - Genetics. Pollen contamination may explain controversial inheritance.

PMID- 17008493
TI  - Geology. Mud eruption threatens villagers in Java.

PMID- 17008494
TI  - Plant science. Parasitic weed uses chemical cues to find host plant.

PMID- 17008495
TI  - Immunology. Study says HIV blood levels don't predict immune decline.

PMID- 17008496
TI  - Cancer. T cells a boon for colon cancer prognosis.

PMID- 17008497
TI  - Stem cells. Scientists create human stem cell line from 'dead' embryos.

PMID- 17008498
TI  - Climate change. Royal Society takes a shot at ExxonMobil.

PMID- 17008499
TI  - Astronomy. Search for giant scope site narrows to two.

PMID- 17008500
TI  - DOE science. Embracing small science in a big way.

PMID- 17008501
TI  - DOE science. A manager who cashes in on consensus.

PMID- 17008502
TI  - DOE science. Ray Orbach asks science to serve society.

PMID- 17008504
TI  - Neuroscience. 'Google of the brain': atlas maps brain's genetic activity.

PMID- 17008503
TI  - Arthur Demarest profile. Living among the Maya, past and present.

PMID- 17008506
TI  - PASCOS 2006. A cosmic-scale test for string theory?

PMID- 17008505
TI  - PASCOS 2006. Neutrino physics probes mysteries of 'flavor' and origins.

PMID- 17008507
TI  - PASCOS 2006. Snapshots from the meeting.

PMID- 17008508
TI  - A fresh look at innovation and security.

PMID- 17008509
TI  - Does the world really need more babies?

PMID- 17008510
TI  - Balancing fertility rates with resources.

PMID- 17008511
TI  - Comment on "Asymmetric coevolutionary networks facilitate biodiversity
      maintenance".
AB  - Bascompte et al. (Reports, 21 April 2006, p. 431) used network asymmetries to
      explain mathematical conditions necessary for stability in historic models of
      mutualism. The Lotka-Volterra equations they used artificially created conditions
      in which some factor, such as asymmetric interaction strengths, is necessary for
      community coexistence. We show that a more realistic model incorporating
      nonlinear functional responses requires no such condition and is consistent with
      their data.

PMID- 17008512
TI  - The early years. Evaluating Montessori education.

PMID- 17008513
TI  - Applied physics. Tuning interface states.

PMID- 17008514
TI  - Geochemistry. Manganese redox chemistry revisited.

PMID- 17008515
TI  - Genomics. Genomics and the tree of life.

PMID- 17008516
TI  - Planetary science. Merging views on Mars.

PMID- 17008517
TI  - Chemistry. Unveiling the membrane domains.

PMID- 17008518
TI  - Immunology. Restless T cells sniff and go.

PMID- 17008521
TI  - The evolution of function & form.

PMID- 17008520
TI  - Mining the molecules that made our mind.

PMID- 17008522
TI  - Casting a genetic light on the evolution of eyes.
AB  - Light has been exploited for information by organisms through the evolution of
      photoreceptors and, ultimately, eyes in animals. Only a handful of eye types
      exist because the physics of light constrains photodetection. In the past few
      years, genetic tools have revealed several parallel pathways through which light
      guides behavior and have provided insights into the convergent evolution of eyes.
      The gene encoding opsin (the primary phototransduction protein) and some
      developmental genes had very early origins and were recruited repeatedly during
      eye evolution. Eye lens proteins arose separately and make up a diverse group,
      many of which were co-opted from other functions. A major challenge now is
      understanding how newly discovered pathways for processing light evolved and how
      they collaborate with eyes to harvest information from light.

PMID- 17008523
TI  - Genomic evolution of Hox gene clusters.
AB  - The family of Hox genes, which number 4 to 48 per genome depending on the animal,
      control morphologies on the main body axis of nearly all metazoans. The
      conventional wisdom is that Hox genes are arranged in chromosomal clusters in
      colinear order with their expression patterns on the body axis. However, recent
      evidence has shown that Hox gene clusters are fragmented, reduced, or expanded in
      many animals-findings that correlate with interesting morphological changes in
      evolution. Hox gene clusters also contain many noncoding RNAs, such as intergenic
      regulatory transcripts and evolutionarily conserved microRNAs, some of whose
      developmental functions have recently been explored.

PMID- 17008524
TI  - Gene regulatory networks in the evolution and development of the heart.
AB  - The heart, an ancient organ and the first to form and function during
      embryogenesis, evolved by the addition of new structures and functions to a
      primitive pump. Heart development is controlled by an evolutionarily conserved
      network of transcription factors that connect signaling pathways with genes for
      muscle growth, patterning, and contractility. During evolution, this ancestral
      gene network was expanded through gene duplication and co-option of additional
      networks. Mutations in components of the cardiac gene network cause congenital
      heart disease, the most common human birth defect. The consequences of such
      mutations reveal the logic of organogenesis and the evolutionary origins of
      morphological complexity.

PMID- 17008525
TI  - Elevated Eocene atmospheric CO2 and its subsequent decline.
AB  - Quantification of the atmospheric concentration of CO2 ([CO2]atm) during warm
      periods of Earth's history is important because burning of fossil fuels may
      produce future [CO2]atm approaching 1000 parts per million by volume (ppm). The
      early Eocene (~56 to 49 million years ago) had the highest prolonged global
      temperatures of the past 65 million years. High Eocene [CO2]atm is established
      from sodium carbonate minerals formed in saline lakes and preserved in the Green
      River Formation, western United States. Coprecipitation of nahcolite (NaHCO3) and
      halite (NaCl) from surface waters in contact with the atmosphere indicates
      [CO2]atm > 1125 ppm (four times preindustrial concentrations), which confirms
      that high [CO2]atm coincided with Eocene warmth.

PMID- 17008527
TI  - Ultrafast vibrational dynamics at water interfaces.
AB  - Time-resolved sum-frequency vibrational spectroscopy permits the study of
      hitherto neglected ultrafast vibrational dynamics of neat water interfaces.
      Measurements on interfacial bonded OH stretch modes revealed relaxation behavior
      on sub-picosecond time scales in close resemblance to that of bulk water.
      Vibrational excitation is followed by spectral diffusion, vibrational relaxation,
      and thermalization in the hydrogen-bonding network. Dephasing of the excitation
      occurs in </=100 femtoseconds. Population relaxation of the dangling OH stretch
      was found to have a time constant of 1.3 picoseconds, the same as that for
      excitation transfer between hydrogen-bonded and unbonded OH stretches of water
      molecules surrounded by acetone.

PMID- 17008526
TI  - The Connectivity Map: using gene-expression signatures to connect small
      molecules, genes, and disease.
AB  - To pursue a systematic approach to the discovery of functional connections among
      diseases, genetic perturbation, and drug action, we have created the first
      installment of a reference collection of gene-expression profiles from cultured
      human cells treated with bioactive small molecules, together with pattern
      matching software to mine these data. We demonstrate that this "Connectivity Map"
      resource can be used to find connections among small molecules sharing a
      mechanism of action, chemicals and physiological processes, and diseases and
      drugs. These results indicate the feasibility of the approach and suggest the
      value of a large-scale community Connectivity Map project.

PMID- 17008528
TI  - Phase separation of lipid membranes analyzed with high-resolution secondary ion
      mass spectrometry.
AB  - Lateral variations in membrane composition are postulated to play a central role
      in many cellular events, but it has been difficult to probe membrane composition
      and organization on length scales of tens to hundreds of nanometers. We present a
      high-resolution imaging secondary ion mass spectrometry technique to reveal the
      lipid distribution within a phase-separated membrane with a lateral resolution of
      approximately 100 nanometers. Quantitative information about the chemical
      composition within small lipid domains was obtained with the use of isotopic
      labels to identify each molecular species. Composition variations were detected
      within some domains.

PMID- 17008529
TI  - Ultrafast carbon-carbon single-bond rotational isomerization in room-temperature
      solution.
AB  - Generally, rotational isomerization about the carbon-carbon single bond in simple
      ethane derivatives in room-temperature solution under thermal equilibrium
      conditions has been too fast to measure. We achieved this goal using two
      dimensional infrared vibrational echo spectroscopy to observe isomerization
      between the gauche and trans conformations of an ethane derivative, 1-fluoro-2
      isocyanato-ethane (1), in a CCl4 solution at room temperature. The isomerization
      time constant is 43 picoseconds (ps, 10(-12) s). Based on this value and on
      density functional theory calculations of the barrier heights of 1, n-butane, and
      ethane, the time constants for n-butane and ethane internal rotation under the
      same conditions are approximately 40 and approximately 12 ps, respectively.

PMID- 17008530
TI  - Soluble Mn(III) in suboxic zones.
AB  - Soluble manganese(III) [Mn(III)] has been thought to disproportionate to soluble
      Mn(II) and particulate Mn(IV)O2 in natural waters, although it persists as
      complexes in laboratory solutions. We report that, in the Black Sea, soluble
      Mn(III) concentrations were as high as 5 micromolar and constituted up to 100% of
      the total dissolved Mn pool. Depth profiles indicated that soluble Mn(III) was
      produced at the top of the suboxic zone by Mn(II) oxidation and at the bottom of
      the suboxic zone by Mn(IV)O2 reduction, then stabilized in each case by unknown
      natural ligands. We also found micromolar concentrations of dissolved Mn(III) in
      the Chesapeake Bay. Dissolved Mn(III) can maintain the existence of suboxic zones
      because it can act as either an electron acceptor or donor. Our data indicate
      that Mn(III) should be ubiquitous at all water column and sediment oxic/anoxic
      interfaces in the environment.

PMID- 17008531
TI  - Type, density, and location of immune cells within human colorectal tumors
      predict clinical outcome.
AB  - The role of the adaptive immune response in controlling the growth and recurrence
      of human tumors has been controversial. We characterized the tumor-infiltrating
      immune cells in large cohorts of human colorectal cancers by gene expression
      profiling and in situ immunohistochemical staining. Collectively, the
      immunological data (the type, density, and location of immune cells within the
      tumor samples) were found to be a better predictor of patient survival than the
      histopathological methods currently used to stage colorectal cancer. The results
      were validated in two additional patient populations. These data support the
      hypothesis that the adaptive immune response influences the behavior of human
      tumors. In situ analysis of tumor-infiltrating immune cells may therefore be a
      valuable prognostic tool in the treatment of colorectal cancer and possibly other
      malignancies.

PMID- 17008532
TI  - Volatile chemical cues guide host location and host selection by parasitic
      plants.
AB  - The importance of plant volatiles in mediating interactions between plant species
      is much debated. Here, we demonstrate that the parasitic plant Cuscuta pentagona
      (dodder) uses volatile cues for host location. Cuscuta pentagona seedlings
      exhibit directed growth toward nearby tomato plants (Lycopersicon esculentum) and
      toward extracted tomato-plant volatiles presented in the absence of other cues.
      Impatiens (Impatiens wallerana) and wheat plants (Triticum aestivum) also elicit
      directed growth. Moreover, seedlings can distinguish tomato and wheat volatiles
      and preferentially grow toward the former. Several individual compounds from
      tomato and wheat elicit directed growth by C. pentagona, whereas one compound
      from wheat is repellent. These findings provide compelling evidence that
      volatiles mediate important ecological interactions among plant species.

PMID- 17008533
TI  - Expression of a bcr-1 isoform of RARalpha-PML does not affect the penetrance of
      acute promyelocytic leukemia or the acquisition of an interstitial deletion on
      mouse chromosome 2.
AB  - Expression of a bcr-3 isoform of retinoic acid receptor alpha-promyelocytic
      leukemia (RARalpha-PML) in mice expressing a bcr-1 isoform of PML-RARalpha is
      associated with increased penetrance of murine acute promyelocytic leukemia (APL)
      and the frequent acquisition of an interstitial deletion of one copy of mouse
      chromosome 2 (del(2)). To determine whether the isoform of RARalpha-PML is
      important for these effects, we created mice that expressed a bcr-1 isoform of
      RARalpha-PML. Coexpression with the bcr-1 isoform of PML-RARalpha did not
      increase the penetrance of APL (7 of 45 animals developed APL with PML-RARalpha
      alone vs 12 of 44 with both transgenes; P=.19). Furthermore, the frequency of
      del(2) in APL cells from doubly transgenic mice was not different from that of
      mice expressing PML-RARalpha alone (3 of 6 vs 6 of 12, respectively-P=1.38
      compared with 11 of 11 for mice coexpressing PML-RARalpha and bcr-3 RARalpha
      PML). The bcr-1 and bcr-3 isoforms of RARalpha-PML, therefore, have different
      biological activities that may be relevant for the pathogenesis of murine APL.

PMID- 17008534
TI  - Tropomyosin modulates erythrocyte membrane stability.
AB  - The ternary complex of spectrin, actin, and 4.1R (human erythrocyte protein 4.1)
      defines the nodes of the erythrocyte membrane skeletal network and is inseparable
      from membrane stability under mechanical stress. These junctions also contain
      tropomyosin (TM) and the other actin-binding proteins, adducin, protein 4.9,
      tropomodulin, and a small proportion of capZ, the functions of which are poorly
      defined. Here, we have examined the consequences of selective elimination of TM
      from the membrane. We have shown that the mechanical stability of the membranes
      of resealed ghosts devoid of TM is grossly, but reversibly, impaired. That the
      decreased membrane stability of TM-depleted membranes is the result of
      destabilization of the ternary complex of the network junctions is demonstrated
      by the strongly facilitated entry into the junctions in situ of a beta-spectrin
      peptide, containing the actin- and 4.1R-binding sites, after extraction of the
      TM. The stabilizing effect of TM is highly specific, in that it is only the
      endogenous isotype, and not the slightly longer muscle TM that can bind to the
      depleted membranes and restore their mechanical stability. These findings have
      enabled us identify a function for TM in elevating the mechanical stability of
      erythrocyte membranes by stabilizing the spectrin-actin-4.1R junctional complex.

PMID- 17008536
TI  - Prophylactic human granulocyte colony-stimulating factor after induction therapy
      in pediatric acute myeloid leukemia.
AB  - Children with acute myelogenous leukemia (AML) have a high risk of infectious
      complications that might be reduced by prophylactic granulocyte colony
      stimulating factor (G-CSF). However, G-CSF could induce AML blast proliferation.
      The prospective randomized trial AML-BFM 98 investigated the impact of G-CSF on
      hematopoetic recovery and infectious complications (primary endpoints) and on
      outcome (secondary endpoint) in children (aged 0-18 years) with de novo AML.
      Patients with more than 5% blasts in day-15 bone marrow or with FAB M3 were not
      included. Between 1998 and 2003, 161 children with AML were randomized to receive
      G-CSF after inductions 1 and 2, whereas 156 patients were assigned to the control
      group. Time of neutropenia after inductions 1 and 2 was significantly shorter in
      the G-CSF group (23 vs 18 days and 16 vs 11 days; P=.02 and=.001, respectively).
      G-CSF did not decrease the incidence of febrile neutropenia (72 and 36 patients
      vs 78 and 37 patients, respectively), microbiologically documented infections (27
      and 25 patients vs 36 and 19 patients, respectively) and infection-associated
      mortality (5 vs 2 patients). Both groups had similar 5-year event-free survival
      (EFS; 59%+/-4% vs 58%+/-4%). Since G-CSF does not influence the risk of
      infectious complications or outcome in children undergoing therapy for AML, one
      cannot advocate the routine use of G-CSF in this patient group.

PMID- 17008535
TI  - Commonly dysregulated genes in murine APL cells.
AB  - To identify genes that are commonly dysregulated in a murine model of acute
      promyelocytic leukemia (APL), we first defined gene expression patterns during
      normal murine myeloid development; serial gene expression profiling studies were
      performed with primary murine hematopoietic progenitors that were induced to
      undergo myeloid maturation in vitro with G-CSF. Many genes were reproducibly
      expressed in restricted developmental "windows," suggesting a structured
      hierarchy of expression that is relevant for the induction of developmental fates
      and/or differentiated cell functions. We compared the normal myeloid
      developmental transcriptome with that of APL cells derived from mice expressing
      PML-RARalpha under control of the murine cathepsin G locus. While many
      promyelocyte-specific genes were highly expressed in all APL samples, 116 genes
      were reproducibly dysregulated in many independent APL samples, including Fos,
      Jun, Egr1, Tnf, and Vcam1. However, this set of commonly dysregulated genes was
      expressed normally in preleukemic, early myeloid cells from the same mouse model,
      suggesting that dysregulation occurs as a "downstream" event during disease
      progression. These studies suggest that the genetic events that lead to APL
      progression may converge on common pathways that are important for leukemia
      pathogenesis.

PMID- 17008537
TI  - Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab
      shows significant clinical activity with low accompanying toxicity in previously
      untreated B chronic lymphocytic leukemia.
AB  - Building on the prior work of use of pentostatin in chronic lymphocytic leukemia
      (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide
      (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated
      patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were
      nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were
      CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by
      fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects.
      Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal
      transfusion needs and no major infections. Responses occurred in 58 patients
      (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses
      (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also
      lacked evidence of minimal residual disease by 2-color flow cytometry.
      Examination of prognostic factors demonstrated poor response in the 3 patients
      with del(17p). In contrast, we found this regimen was equally effective in young
      versus older (>70 years) patients and in del(11q22.3) versus other favorable
      prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide,
      and rituximab for previously untreated patients with CLL demonstrated significant
      clinical activity despite poor risk-based prognoses, achievement of minimal
      residual disease in some, and modest toxicity.

PMID- 17008538
TI  - The activity of lenalidomide with or without dexamethasone in patients with
      primary systemic amyloidosis.
AB  - Primary systemic amyloidosis (AL) is an incurable plasma cell disorder.
      Lenalidomide, especially in conjunction with dexamethasone, is highly active in
      patients with multiple myeloma. We studied the toxicity and efficacy of
      lenalidomide in patients with AL. Patients with symptomatic AL, a measurable
      plasma cell disorder, and adequate hematologic and renal reserve were eligible.
      Patients received single-agent lenalidomide. If there was no evidence of
      progression after 3 months or of hematologic response after 3 cycles,
      dexamethasone was added. Twenty-three patients were enrolled. Thirteen were
      previously treated. Organ involvement was cardiac (64%), renal (73%), hepatic
      (23%), and nerve (14%). Within the first 3 cycles of therapy, 10 patients
      discontinued treatment: 4 early deaths, 3 adverse events, and 3 other causes.
      With a median follow-up of 17 months, 10 patients responded to treatment. In
      these patients, responses included 9 hematologic, 4 renal, 2 cardiac, and 2
      hepatic. All but one of the responders had dexamethasone added to their treatment
      program. The most common grade 3 or 4 adverse events at least possibly
      attributable to lenalidomide were neutropenia (45%), thrombocytopenia (27%), rash
      (18%), and fatigue (18%). In AL patients, we saw limited activity of single-agent
      lenalidomide, but significant activity of the combination with dexamethasone,
      which warrants further investigation.

PMID- 17008539
TI  - Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML):
      biologic and clinical features.
AB  - The nucleophosmin (NPM1) gene encodes for a multifunctional nucleocytoplasmic
      shuttling protein that is localized mainly in the nucleolus. NPM1 mutations occur
      in 50% to 60% of adult acute myeloid leukemia with normal karyotype (AML-NK) and
      generate NPM mutants that localize aberrantly in the leukemic-cell cytoplasm,
      hence the term NPM-cytoplasmic positive (NPMc+ AML). Cytoplasmic NPM accumulation
      is caused by the concerted action of 2 alterations at mutant C-terminus, that is,
      changes of tryptophan(s) 288 and 290 (or only 290) and creation of an additional
      nuclear export signal (NES) motif. NPMc+ AML shows increased frequency in adults
      and females, wide morphologic spectrum, multilineage involvement, high frequency
      of FLT3-ITD, CD34 negativity, and a distinct gene-expression profile. Analysis of
      mutated NPM has important clinical and pathologic applications.
      Immunohistochemical detection of cytoplasmic NPM predicts NPM1 mutations and
      helps rationalize cytogenetic/molecular studies in AML. NPM1 mutations in absence
      of FLT3-ITD identify a prognostically favorable subgroup in the heterogeneous AML
      NK category. Due to their frequency and stability, NPM1 mutations may become a
      new tool for monitoring minimal residual disease in AML-NK. Future studies should
      focus on clarifying how NPM mutants promote leukemia, integrating NPMc+ AML in
      the upcoming World Health Organization leukemia classification, and eventually
      developing specific antileukemic drugs.

PMID- 17008540
TI  - Beyond HLA: the significance of genomic variation for allogeneic hematopoietic
      stem cell transplantation.
AB  - The last 2 years have seen much excitement in the field of genetics with the
      identification of a formerly unappreciated level of "structural variation" within
      the normal human genome. Genetic structural variants include deletions,
      duplications, and inversions in addition to the recently discovered, copy number
      variants. Single nucleotide polymorphisms are the most extensively evaluated
      variant within the genome to date. Combining our knowledge from these studies
      with our rapidly accumulating understanding of structural variants, it is
      apparent that the extent of genetic dissimilarity between any 2 individuals is
      considerable and much greater than that which was previously recognized. Clearly,
      this more diverse view of the genome has significant implications for allogeneic
      hematopoietic stem cell transplantation, not least in the generation of
      transplant antigens but also in terms of individual susceptibility to transplant
      related toxicities. With advances in DNA sequencing technology we now have the
      capacity to perform genome-wide analysis in a high throughput fashion, permitting
      a detailed genetic analysis of patient and donor prior to transplantation.
      Understanding the significance of this additional genetic information and
      applying it in a clinically meaningful way will be one of the challenges faced by
      transplant clinicians in the future.

PMID- 17008541
TI  - Glycoprotein Ibalpha forms disulfide bonds with 2 glycoprotein Ibbeta subunits in
      the resting platelet.
AB  - It is widely accepted that glycoprotein (GP) Ib contains one Ibalpha and one
      Ibbeta subunit that are connected by a disulfide bond. It is unclear which Cys
      residue in Ibalpha, C484 or C485, forms the disulfide bond with Ibbeta. Using
      mutagenesis studies in transfected Chinese hamster ovary (CHO) cells, we found
      that both C484 and C485 formed a disulfide bond with C122 in Ibbeta. In the
      context of isolated peptides containing the Ibalpha or Ibbeta transmembrane
      domain and nearby Cys residue, C484 and C485 in the Ibalpha peptide were both
      capable of forming a disulfide bond with the Ibbeta peptide. Furthermore,
      coimmunoprecipitation of epitope-tagged subunits showed that at least 2 Ibbeta
      subunits but only 1 Ibalpha and 1 IX subunit were present in the GP Ib-IX
      complex. Finally, the size difference between GP Ib from transfected CHO cells
      and human platelets was attributed to a combination of sequence polymorphism and
      glycosylation difference in Ibalpha, not the number of Ibbeta subunits therein.
      Overall, these results demonstrate that Ibalpha is covalently connected to 2
      Ibbeta subunits in the resting platelet, necessitating revision of the subunit
      stoichiometry of the GP Ib-IX-V complex. The alphabeta2 composition in GP Ib may
      provide the basis for possible disulfide rearrangement in the receptor complex.

PMID- 17008543
TI  - PDGFRalpha-expressing mesenchyme regulates thymus growth and the availability of
      intrathymic niches.
AB  - The thymus provides a specialized site for the production of T cells capable of
      recognizing foreign antigens in the context of self-major histocompatibility
      complex (MHC) molecules. During development, the thymus arises from an epithelial
      rudiment containing bipotent progenitors that differentiate into distinct
      cortical and medullary epithelial cells to regulate the maturation and selection
      of self-tolerant CD4+ and CD8+ T cells. In addition to their differentiation,
      thymic epithelial cells undergo cellular expansion to ensure that sufficient
      intrathymic cellular niches are available to support the large number of immature
      thymocytes required to form a self-tolerant T-cell pool. Thus, intrathymic T-cell
      production is intimately linked to the formation and availability of niches
      within thymic microenvironments. Here, we show the increase in intrathymic niches
      caused by the proliferation of the epithelium in the developing thymus is
      temporally regulated, and correlates with the presence of a population of fetal
      thymic mesenchyme defined by platelet-derived growth factor receptor alpha
      (PDGFRalpha) expression. Depletion of PDGFRalpha+ mesenchyme from embryonic thymi
      prior to their transplantation to ectopic sites results in the formation of
      functional yet hypoplastic thymic tissue. In summary, we highlight a specialized
      role for PDGFRalpha+ fetal mesenchyme in the thymus by determining availability
      of thymic niches through the regulation of thymic epithelial proliferation.

PMID- 17008542
TI  - PI3K regulates pleckstrin-2 in T-cell cytoskeletal reorganization.
AB  - Pleckstrin-2 is composed of 2 pleckstrin homology (PH) domains and a disheveled
      Egl-10-pleckstrin (DEP) domain. A lipid-binding assay revealed that pleckstrin-2
      binds with greatest affinity to D3 and D5 phosphoinositides. Pleckstrin-2
      expressed in Jurkat T cells bound to the cellular membrane and enhanced actin
      dependent spreading only after stimulation of the T-cell antigen receptor or the
      integrin alpha4beta1. A pleckstrin-2 variant containing point mutations in both
      PH domains failed to associate with the Jurkat membrane and had no effect on
      spreading under the same conditions. Although still membrane bound, a pleckstrin
      2 variant containing point mutations in the DEP domain demonstrated a decreased
      ability to induce membrane ruffles and spread. Pleckstrin-2 also colocalized with
      actin at the immune synapse and integrin clusters via its PH domains. Although
      pleckstrin-2 can bind to purified D3 and D5 phosphoinositides, the intracellular
      membrane association of pleckstrin-2 and cell spreading are dependent on D3
      phosphoinositides, because these effects were disrupted by pharmacologic
      inhibition of phosphatidylinositol 3-kinase (PI3K). Our results indicate that
      pleckstrin-2 uses its modular domains to bind to membrane-associated
      phosphatidylinositols generated by PI3K, whereby it coordinates with the actin
      cytoskeleton in lymphocyte spreading and immune synapse formation.

PMID- 17008544
TI  - CD33 responses are blocked by SOCS3 through accelerated proteasomal-mediated
      turnover.
AB  - CD33 is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec)
      family of inhibitory receptors and a therapeutic target for acute myeloid
      leukemia (AML). CD33 contains a cytoplasmic immunoreceptor tyrosine-based
      inhibitory motif (ITIM), which can recruit SHP-1 and SHP-2. How CD33 expression
      is regulated is unclear. Suppressor of cytokine signaling 3 (SOCS3) is expressed
      in response to cytokines, LPS, and other PAMPs, and competes with SHP-1/2 binding
      to ITIMs of cytokine receptors, thereby inhibiting signaling. In this study,
      using peptide pull-down experiments, we found that SOCS3 can specifically bind to
      the phosphorylated ITIM of CD33. Additionally, following cross-linking SOCS3 can
      recruit the ECS E3 ligase resulting in accelerated proteasomal degradation of
      both CD33 and SOCS3. Our data suggest that the tyrosine motifs in CD33 are not
      important for internalization, while they are required for degradation. Moreover,
      SOCS3 inhibited the CD33-induced block on cytokine-induced proliferation. This is
      the first receptor shown to be degraded by SOCS3 and where SOCS3 and its target
      protein are degraded concomitantly. Our findings clearly suggest that during an
      inflammatory response, the inhibitory receptor CD33 is lost by this mechanism.
      Moreover, this has important clinical implications as tumors expressing SOCS3 may
      be refractory to alpha-CD33 therapy.

PMID- 17008545
TI  - Attenuation of phagocytosis of xenogeneic cells by manipulating CD47.
AB  - Signal regulatory protein alpha (SIRPalpha) is a critical immune inhibitory
      receptor on macrophages, and its interaction with CD47, a ligand for SIRPalpha,
      prevents autologous phagocytosis. We hypothesized that interspecies
      incompatibility of CD47 may contribute to the rejection of xenogeneic cells by
      macrophages. Here, we show that pig CD47 does not interact with mouse SIPRalpha.
      Similar to CD47-/- mouse cells, porcine red blood cells (RBCs) failed to induce
      SIRPalpha tyrosine phosphorylation in mouse macrophages. Blocking SIRPalpha with
      antimouse SIRPalpha mAb (P84) significantly enhanced the phagocytosis of CD47+/+
      mouse cells, but did not affect the engulfment of porcine or CD47-/- mouse cells
      by mouse macrophages. CD47-deficient mice, whose macrophages do not phagocytose
      CD47-/- mouse cells, showed markedly delayed clearance of porcine RBCs compared
      with wild-type mouse recipients. Furthermore, mouse CD47 expression on porcine
      cells markedly reduced their phagocytosis by mouse macrophages both in vitro and
      in vivo. These results indicate that interspecies incompatibility of CD47
      contributes significantly to phagocytosis of xenogeneic cells by macrophages and
      suggest that genetic manipulation of donor CD47 to improve its interaction with
      the recipient SIRPalpha may provide a novel approach to prevent phagocyte
      mediated xenograft rejection.

PMID- 17008546
TI  - Histone deacetylase activities are required for innate immune cell control of Th1
      but not Th2 effector cell function.
AB  - Histone deacetylases (HDACs) play a critical role in regulating gene expression
      and key biological processes. However, how HDACs are involved in innate immunity
      is little understood. Here, in this first systematic investigation of the role of
      HDACs in immunity, we show that HDAC inhibition by a small-molecule HDAC
      inhibitor (HDACi), LAQ824, alters Toll-like receptor 4 (TLR4)-dependent
      activation and function of macrophages and dendritic cells (DCs). Surprisingly,
      pan-HDAC inhibition modulates only a limited set of genes involved in distinct
      arms of immune responses. Specifically, it inhibited DC-controlled T helper 1
      (Th1) effector but not Th2 effector cell activation and migration. It also
      inhibited macrophage- and DC-mediated monocyte but not neutrophil chemotaxis.
      These unexpected findings demonstrate the high specificity of HDAC inhibition in
      modulating innate and adaptive immune responses, and highlight the potential for
      HDACi to alter the Th1 and Th2 balance in therapeutic settings.

PMID- 17008547
TI  - Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB
      activation in dendritic cells.
AB  - Dendritic cells (DCs) play a key role in immune homeostasis and maintenance of
      self-tolerance. Tolerogenic DCs can be established by an encounter with apoptotic
      cells (ACs) and subsequent inhibition of maturation and effector functions. The
      receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DCs
      have yet to be defined. We demonstrate that pretreatment with apoptotic but not
      necrotic cells inhibits activation of IkappaB kinase (IKK) and downstream NF
      kappaB. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is required
      for mediating this effect. Monocyte-derived DCs lacking MerTK expression
      (MerTKKD) or treated with blocking MerTK-specific antibodies (Abs) are resistant
      to AC-induced inhibition and continue to activate NF-kappaB and secrete
      proinflammatory cytokines. Blocking MerTK activation of the phosphatidylinositol
      3-kinase (PI3K)/AKT pathway prevents AC-induced inhibition. These results
      demonstrate an essential role for MerTK-mediated regulation of the PI3K/AKT and
      NF-kappaB pathways in AC-induced inhibition of monocyte-derived DCs.

PMID- 17008548
TI  - The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2
      independently of sphingosine-1-phosphate receptors.
AB  - FTY720 is a potent immunomodulator drug that inhibits the egress of lymphocytes
      from secondary lymphoid tissues and thymus. FTY720 is phosphorylated in vivo by
      sphingosine kinase 2 to FTY720-phosphate, which acts as a potent sphingosine-1
      phosphate (S1P) receptor agonist. However, in contrast to S1P, FTY720 has no
      effect on mast-cell degranulation, yet significantly reduces antigen-induced
      secretion of PGD2 and cysteinyl-leukotriene. Unexpectedly, this effect of FTY720
      was independent of its phosphorylation and S1P receptor functions. The rate
      limiting step in the biosynthesis of all eicosanoids is the phospholipase A2
      (PLA2)-mediated release of arachidonic acid from glycerol phospholipids. Although
      FTY720 also reduced arachidonic acid release in response to antigen, it had no
      effect on translocation of cPLA2 or ERK1/2 activation, suggesting that it does
      not interfere with FcepsilonRI-mediated events leading to cPLA2 activation.
      Remarkably, however, FTY720 drastically inhibited recombinant cPLA2alpha
      activity, whereas FTY720-phosphate, sphingosine, or S1P had no effect. This study
      has uncovered a unique action of FTY720 as an inhibitor of cPLA2alpha and hence
      on production of all eicosanoids. Our results have important implications for the
      potential therapeutic mechanism of action of FTY720 in eicosanoid-driven
      inflammatory disorders such as asthma and multiple sclerosis.

PMID- 17008549
TI  - Annexin-1 modulates T-cell activation and differentiation.
AB  - Annexin-1 is an anti-inflammatory protein that plays an important homeostatic
      role in innate immunity; however, its potential actions in the modulation of
      adaptive immunity have never been explored. Although inactive by itself, addition
      of annexin-1 to stimulated T cells augmented anti-CD3/CD28-mediated CD25 and CD69
      expression and cell proliferation. This effect was paralleled by increased
      nuclear factor-kappaB (NF-kappaB), nuclear factor of activated T cells (NFATs),
      and activator protein-1 (AP-1) activation and preceded by a rapid T-cell receptor
      (TCR)-induced externalization of the annexin-1 receptor. Interestingly,
      differentiation of naive T cells in the presence of annexin-1 increased skewing
      in Th1 cells; in the collagen-induced arthritis model, treatment of mice with
      annexin-1 during the immunization phase exacerbated signs and symptoms at disease
      onset. Consistent with these findings, blood CD4+ cells from patients with
      rheumatoid arthritis showed a marked up-regulation of annexin-1 expression.
      Together these results demonstrate that annexin-1 is a molecular "tuner" of TCR
      signaling and suggest this protein might represent a new target for the
      development of drugs directed to pathologies where an unbalanced Th1/Th2 response
      or an aberrant activation of T cells is the major etiologic factor.

PMID- 17008550
TI  - Promoter SNPs in G1/S checkpoint regulators and their impact on the
      susceptibility to childhood leukemia.
AB  - Mutations leading to the alteration of cell-cycle checkpoint functions are a
      common feature of most cancers. Because of the highly regulated nature of the
      cell cycle, it seems likely that variation in gene dosage of key components due
      to functional regulatory polymorphisms could play an important role in cancer
      development. Here we provide evidence of the involvement of promoter single
      nucleotide polymorphisms (pSNPs) in the cyclin-dependent-kinase inhibitor genes
      CDKN2A, CDKN2B, CDKN1A, and CDKN1B in the etiology of childhood pre-B acute
      lymphoblastic leukemia (ALL). A case-control study, conducted in 240 patients
      with pre-B ALL and 277 healthy controls, combined with a family-based analysis
      using 135 parental trios, all of French-Canadian origin, were used to evaluate
      single-site genotypic as well as multilocus haplotypic associations for a total
      of 10 pSNPs. Using both study designs, we showed evidence of association between
      variants CDKN2A -222A, CDKN2B -593A, and CDKN1B -1608A, and an increased risk of
      ALL. These findings suggest that variable expression levels of cell-cycle
      inhibitor genes CDKN2A, CDKN2B, and CDKN1B due to regulatory polymorphisms could
      indeed influence the risk of childhood pre-B ALL and contribute to
      carcinogenesis.

PMID- 17008551
TI  - The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell
      migration.
AB  - Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM)
      involve a complex interplay between chemokines, cytokines, and nonpeptide
      molecules. Extracellular nucleotides and their cognate P2 receptors are emerging
      as key factors of inflammation and related chemotactic responses. In this study,
      we investigated the activity of extracellular adenosine triphosphate (ATP) and
      uridine triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis. In vitro,
      UTP significantly improved HSC migration, inhibited cell membrane CXCR4 down
      regulation by migrating CD34+ cells, and increased cell adhesion to fibronectin.
      In vivo, preincubation with UTP significantly enhanced the BM homing efficiency
      of human CD34+ cells in immunodeficient mice. Pertussis toxin blocked CXCL12- and
      UTP-dependent chemotactic responses, suggesting that G-protein alpha-subunits
      (Galphai) may provide a converging signal for CXCR4- and P2Y-activated
      transduction pathways. In addition, gene expression profiling of UTP- and CXCL12
      treated CD34+ cells and in vitro inhibition assays demonstrated that Rho
      guanosine 5'-triphosphatase (GTPase) Rac2 and downstream effectors Rho GTPase
      activated kinases 1 and 2 (ROCK1/2) are involved in UTP-promoted/CXCL12-dependent
      HSC migration. Our data suggest that UTP may physiologically modulate the homing
      of HSCs to the BM, in concert with CXCL12, via the activation of converging
      signaling pathways between CXCR4 and P2Y receptors, involving Galphai proteins
      and RhoGTPases.

PMID- 17008552
TI  - Hypusination of eukaryotic initiation factor 5A (eIF5A): a novel therapeutic
      target in BCR-ABL-positive leukemias identified by a proteomics approach.
AB  - Inhibition of BCR-ABL tyrosine kinase with imatinib represents a major
      breakthrough in the treatment of patients with chronic myeloid leukemia (CML).
      However, resistance to imatinib develops frequently, particularly in late-stage
      disease. To identify new cellular BCR-ABL downstream targets, we analyzed
      differences in global protein expression in BCR-ABL-positive K562 cells treated
      with or without imatinib in vitro. Among the 19 proteins found to be
      differentially expressed, we detected the down-regulation of eukaryotic
      initiation factor 5A (eIF5A), a protein essential for cell proliferation. eIF5A
      represents the only known eukaryotic protein activated by posttranslational
      hypusination. Hypusination inhibitors (HIs) alone exerted an antiproliferative
      effect on BCR-ABL-positive and -negative leukemia cell lines in vitro. However,
      the synergistic dose-response relationship found for the combination of imatinib
      and HI was restricted to Bcr-Abl-positive cells. Furthermore, this synergistic
      effect was confirmed by cytotoxicity assays, cell-cycle analysis, and CFSE
      labeling of primary CD34+ CML cells. Specificity of this effect could be
      demonstrated by cotreatment of K562 cells with imatinib and siRNA against eIF5.
      In conclusion, through a comparative proteomics approach and further functional
      analysis, we identified the inhibition of eIF5A hypusination as a promising new
      approach for combination therapy in BCR-ABL-positive leukemias.

PMID- 17008553
TI  - Mucosal stimulation activates secretomotor neurons via long myenteric pathways in
      guinea pig ileum.
AB  - This study examined whether mucosal stimulation activates long secretomotor
      neural reflexes and, if so, how they are organized. The submucosa of in vitro
      full thickness guinea pig ileal preparations was exposed in the distal portion
      and intracellular recordings were obtained from electrophysiologically identified
      secretomotor neurons. Axons in the intact mucosa of the oral segment were
      stimulated by a large bipolar stimulating electrode. In control preparations, a
      single stimulus pulse evoked a fast excitatory postsynaptic potential (EPSP) in
      86% of neurons located 0.7-1.0 cm anal to the stimulus site. A stimulus train
      evoked multiple fast EPSPs, but slow EPSPs were not observed. To examine whether
      mucosal stimulation specifically activated mucosal sensory nerve terminals, the
      mucosa/submucosa was severed from the underlying layers and repositioned. In
      these preparations, fast EPSPs could not be elicited in 89% of cells. Superfusion
      with phorbol dibutyrate enhanced excitability of sensory neurons and pressure
      pulse application of serotonin to the mucosa increased the fast EPSPs evoked by
      mucosal stimulation, providing further evidence that sensory neurons were
      involved. To determine whether these reflexes projected through the myenteric
      plexus, this plexus was surgically lesioned between the stimulus site and the
      impaled neuron. No fast EPSPs were recorded in these preparations following
      mucosal stimulation whereas lesioning the submucosal plexus had no effect. These
      results demonstrate that mucosal stimulation triggers a long myenteric pathway
      that activates submucosal secretomotor neurons. This pathway projects in parallel
      with motor and vasodilator reflexes, and this common pathway may enable
      coordination of intestinal secretion, blood flow, and motility.

PMID- 17008554
TI  - Persistent alterations to enteric neural signaling in the guinea pig colon
      following the resolution of colitis.
AB  - Functional changes induced by inflammation persist following recovery from the
      inflammatory response, but the mechanisms underlying these changes are not well
      understood. Our aim was to investigate whether the excitability and synaptic
      properties of submucosal neurons remained altered 8 wk post-trinitrobenzene
      sulfonic acid (TNBS) treatment and to determine whether these changes were
      accompanied by alterations in secretory function in submucosal preparations
      voltage clamped in Ussing chambers. Mucosal serotonin (5-HT) release measurements
      and 5-HT reuptake transporter (SERT) immunohistochemistry were also performed.
      Eight weeks after TNBS treatment, colonic inflammation resolved, as assessed
      macroscopically and by myeloperoxidase assay. However, fast excitatory
      postsynaptic potential (fEPSP) amplitude was significantly increased in
      submucosal S neurons from previously inflamed colons relative to those in control
      tissue. In addition, fEPSPs from previously inflamed colons had a hexamethonium
      insensitive component that was not evident in age-matched controls. AH neurons
      were hyperexcitable, had shorter action potential durations, and decreased
      afterhyperpolarization 8 wk following TNBS adminstration. Neuronally mediated
      colonic secretory function was significantly reduced after TNBS treatment,
      although epithelial cell signaling, as measured by responsiveness to both
      forskolin and bethanecol in the presence of tetrodotoxin, was comparable with
      control tissue. 5-HT levels and SERT immunoreactivity were comparable to controls
      8 wk after the induction of inflammation, but there was an increase in glucagon
      like peptide 2-immunoreactive L cells. In conclusion, sustained alterations in
      enteric neural signaling occur following the resolution of colitis, which are
      accompanied by functional changes in the absence of active inflammation.

PMID- 17008555
TI  - Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of
      sterol regulatory element binding protein 2.
AB  - Niemann-Pick C1-like 1 (NPC1L1) is an essential intestinal component of
      cholesterol absorption. However, little is known about the molecular regulation
      of intestinal NPC1L1 expression and promoter activity. We demonstrated that human
      NPC1L1 mRNA expression was significantly decreased by 25-hydroxycholesterol but
      increased in response to cellular cholesterol depletion achieved by incubation
      with Mevinolin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase) in
      human intestinal Caco-2 cells. We also showed that a -1741/+56 fragment of the
      NPC1L1 gene demonstrated high promoter activity in Caco-2 cells that was reduced
      by 25-hydroxycholesterol and stimulated by cholesterol depletion. Interestingly,
      we showed that the NPC1L1 promoter is remarkably transactivated by the
      overexpression of sterol regulatory element (SRE) binding protein (SREBP)-2,
      suggesting its involvement in the sterol-induced alteration in NPC1L1 promoter
      activity. Finally, we identified two putative SREs in the human NPC1L1 promoter
      and established their essential roles in mediating the effects of cholesterol on
      promoter activity. Our study demonstrated the modulation of human NPC1L1
      expression and promoter activity by cholesterol in a SREBP-2-dependent mechanism.

PMID- 17008556
TI  - Both Ca2+ -dependent and -independent pathways are involved in rat hepatic
      stellate cell contraction and intrahepatic hyperresponsiveness to methoxamine.
AB  - In chronic liver injury, hepatic stellate cells (HSCs) have been implicated as
      regulators of sinusoidal vascular tone. We studied the relative role of Ca(2+)
      dependent and Ca(2+)-independent contraction pathways in rat HSCs and correlated
      these findings to in situ perfused cirrhotic rat livers. Contraction of primary
      rat HSCs was studied by a stress-relaxed collagen lattice model. Dose-response
      curves to the Ca(2+) ionophore A-23187 and to the calmodulin/myosin light chain
      kinase inhibitor W-7 served to study Ca(2+)-dependent pathways. Y-27632,
      staurosporin, and calyculin (inhibitors of Rho kinase, protein kinase C, and
      myosin light chain phosphatase, respectively) were used to investigate Ca(2+)
      independent pathways. The actomyosin interaction, the common end target, was
      inhibited by 2,3-butanedione monoxime. Additionally, the effects of W-7, Y-27632,
      and staurosporin on intrahepatic vascular resistance were evaluated by in situ
      perfusion of normal and thioacetamide-treated cirrhotic rat livers stimulated
      with methoxamine (n = 25 each). In vitro, HSC contraction was shown to be
      actomyosin based with a regulating role for both Ca(2+)-dependent and 
      independent pathways. Although the former seem important, an important auxiliary
      role for the latter was illustrated through their involvement in the phenomenon
      of "Ca(2+) sensitization." In vivo, preincubation of cirrhotic livers with Y
      27632 (10(-4) M) and staurosporin (25 nM), more than with W-7 (10(-4) M),
      significantly reduced the hyperresponsiveness to methoxamine (10(-4) M) by -66.8
      +/- 1.3%, -52.4 +/- 2.7%, and -28.7 +/- 2.8%, respectively, whereas in normal
      livers this was significantly less: -43.1 +/- 4.2%, -40.2 +/- 4.2%, and -3.8 +/-
      6.3%, respectively. Taken together, these results suggest that HSC contraction is
      based on both Ca(2+)-dependent and -independent pathways, which were shown to be
      upregulated in the perfused cirrhotic liver, with a predominance of Ca(2+)
      independent pathways.

PMID- 17008557
TI  - M2 and M3 muscarinic receptors are involved in enteric nerve-mediated contraction
      of the mouse ileum: Findings obtained with muscarinic-receptor knockout mouse.
AB  - The involvement of muscarinic receptors in neurogenic responses of the ileum was
      studied in wild-type and muscarinic-receptor (M-receptor) knockout (KO) mice.
      Electrical field stimulation to the wild-type mouse ileum induced a biphasic
      response, a phasic and sustained contraction that was abolished by tetrodotoxin.
      The sustained contraction was prolonged for an extended period after the
      termination of electrical field stimulation. The phasic contraction was
      completely inhibited by atropine. In contrast, the sustained contraction was
      enhanced by atropine. Ileal strips prepared from M2-receptor KO mice exhibited a
      phasic contraction similar to that seen in wild-type mice and a sustained
      contraction that was larger than that in wild-type mice. In M3-receptor KO mice,
      the phasic contraction was smaller than that observed in wild-type mice.
      Acetylcholine exogenously administrated induced concentration-dependent
      contractions in strips isolated from wild-type, M2- and M3-receptor KO mice.
      However, contractions in M3-receptor KO mice shifted to the right. The sustained
      contraction was inhibited by capsaicin and neurokinin NK2 receptor antagonist,
      suggesting that it is mediated by substance P (SP). SP-induced contraction of M2
      receptor KO mice did not differ from that of wild-type mice. SP immunoreactivity
      was located in enteric neurons, colocalized with M2 receptor immunoreactivity.
      These results suggest that atropine-sensitive phasic contraction is mainly
      mediated via the M3 receptor, and SP-mediated sustained contraction is negatively
      regulated by the M2 receptor at a presynaptic level.

PMID- 17008558
TI  - Short-form Ron receptor is required for normal IFN-gamma production in
      concanavalin A-induced acute liver injury.
AB  - Abrogation of Ron receptor tyrosine kinase function results in defects in
      macrophage activation and dysregulated acute inflammatory responses in vivo.
      Several naturally occurring constitutively active alternative forms of Ron have
      been identified, including from primary human tumors and tumor cell lines. One of
      these alternative forms, short-form (SF) Ron, is generated from an alternative
      start site in intron 10 of the Ron gene that eliminates most of the extracellular
      portion of the receptor and is overexpressed in several human cancers. To test
      the physiological significance of SF-Ron in vivo, mice were generated that solely
      express the full-length form of Ron (FL-Ron). Our results show that elimination
      of the capacity to express SF-Ron in vivo leads to augmented production of IFN
      gamma from splenocytes following stimulation ex vivo with either concanavalin A
      or anti-CD3/T cell receptor monoclonal antibody. Moreover, in a concanavalin A
      induced murine model of acute liver injury, FL-Ron mice have increased production
      of serum INF-gamma and serum alanine aminotransferase levels and worsened liver
      histology and overall survival compared with wild-type control mice. Taken
      together, these results suggest for the first time that SF-Ron impacts the
      progression of inflammatory immune responses in vivo and further support a role
      for the Ron receptor and its various forms in liver pathophysiology.

PMID- 17008559
TI  - We must fight HIV/AIDS with science, not politics.

PMID- 17008560
TI  - The Poussaint-Satcher-Cosby chair in mental health: creating activists on behalf
      of our communities, our youths, and ourselves.

PMID- 17008561
TI  - Communal housing settings enhance substance abuse recovery.
AB  - Oxford Houses are democratic, mutual help-oriented recovery homes for individuals
      with substance abuse histories. There are more than 1200 of these houses in the
      United States, and each home is operated independently by its residents, without
      help from professional staff. In a recent experiment, 150 individuals in Illinois
      were randomly assigned to either an Oxford House or usual-care condition (i.e.,
      outpatient treatment or self-help groups) after substance abuse treatment
      discharge. At the 24-month follow-up, those in the Oxford House condition
      compared with the usual-care condition had significantly lower substance use,
      significantly higher monthly income, and significantly lower incarceration rates.

PMID- 17008562
TI  - Prisons and health reforms in England and Wales.
AB  - Prison health in England and Wales has seen rapid reform and modernization.
      Previously it was characterized by over-medicalization, difficulties in staff
      recruitment, and a lack of professional development for staff. The Department of
      Health assumed responsibility from Her Majesty's Prison Service for health
      policymaking in 2000, and full budgetary and health care administration control
      were transferred by April 2006. As a result of this reorganization, funding has
      improved and services now relate more to assessed health need. There is early but
      limited evidence that some standards of care and patient outcomes have improved.
      The reforms address a human rights issue: that prisoners have a right to expect
      their health needs to be met by services that are broadly equivalent to services
      available to the community at large. We consider learning points for other
      countries which may be contemplating prison health reform, particularly those
      with a universal health care system.

PMID- 17008563
TI  - Privatization of public services: organizational reform efforts in public
      education and public health.
AB  - The public health and the public education systems in the United States have
      encountered problems in quality of service, accountability, and availability of
      resources. Both systems are under pressure to adopt the general organizational
      reform of privatization. The debate over privatization in public education is
      contentious, but in public health, the shift of functions from the public to the
      private sector has been accepted with limited deliberation. We assess the
      benefits and concerns of privatization and suggest that shifting public health
      functions to the private sector raises questions about the values and mission of
      public health. Public health officials need to be more engaged in a public debate
      over the desirability of privatization as the future of public health.

PMID- 17008564
TI  - Mental hygiene. 1916.

PMID- 17008565
TI  - Thomas W. Salmon: advocate of mental hygiene.

PMID- 17008566
TI  - Freeing the insane.

PMID- 17008567
TI  - US suicide rates by age group, 1970-2002: an examination of recent trends.
AB  - US suicide rates have declined in recent years, reversing earlier trends. We
      examined suicide rates among 4 age groups from 1970 to 2002 and the factors that
      may have contributed to the decline. We paid particular attention to newer anti
      depressants because of recent concerns and controversy about a possible
      association with suicidal behaviors. These trends warrant more extensive analysis
      of suicide rates among specific subgroups, including consideration of additional
      variables that may influence rates differentially. The relative contributions of
      depression diagnosis and treatment, postsuicide attempt care, and other
      contextual factors (e.g., overall economic conditions) also deserve attention. If
      the decline is associated with contextual factors, clarifying these associations
      will better inform public policy decisions and contribute to more effective
      interventions for preventing suicide.

PMID- 17008568
TI  - Opioid analgesic involvement in drug abuse deaths in American metropolitan areas.
AB  - I measured the role of opioid analgesics in drug abuse-related deaths in a
      consistent panel of 28 metropolitan areas from the Drug Abuse Warning Network.
      The number of reports of opioid analgesics increased 96.6% from 1997 to 2002;
      methadone, oxycodone, and unspecified opioid analgesics accounted for 74.3% of
      the increase. Oxycodone reports increased 727.8% (from 72 to 596 reports). By
      2002, opioid analgesics were noted more frequently than were heroin or cocaine.
      Dramatic increases in the availability of such opioids have made their abuse a
      major, growing problem.

PMID- 17008569
TI  - Sudden infant death syndrome and reported maternal smoking during pregnancy.
AB  - We investigated the effect of maternal smoking during pregnancy on the relative
      risk of sudden infant death syndrome (SIDS) by linking data from Georgia birth
      and death certificates from 1997 to 2000. We estimated the effect of
      misclassifying smokers as non-smokers and the effect of being misclassified on
      SIDS rates, and we calculated the fraction of cases caused by exposure. Of all
      SIDS cases, 21% were attributable to maternal smoking; among smokers, 61% of SIDS
      cases were attributable to maternal smoking. Maternal smoking during pregnancy is
      associated with a significantly increased risk of SIDS.

PMID- 17008570
TI  - Incarceration as forced migration: effects on selected community health outcomes.
AB  - OBJECTIVES: We estimated the effects of high incarceration rates on rates of
      sexually transmitted infections and teenage pregnancies. METHODS: We calculated
      correlations between rates of incarceration in state prisons and county jails and
      rates of sexually transmitted infections and teenage pregnancies for each of the
      100 counties in North Carolina during 1995 to 2002. We also estimated increases
      in negative health outcomes associated with increases in incarceration rates
      using negative binomial regression analyses. RESULTS: Rates of sexually
      transmitted infections and teenage pregnancies, adjusted for age, race, and
      poverty distributions by county, consistently increased with increasing
      incarceration rates. In the most extreme case, teenage pregnancies exhibited an
      increase of 71.61 per 100000 population (95% confidence interval [CI]=41.88,
      101.35) in 1996 after an increase in the prison population rate from 223.31 to
      468.58 per 100000 population in 1995. CONCLUSIONS: High rates of incarceration
      can have the unintended consequence of destabilizing communities and contributing
      to adverse health outcomes.

PMID- 17008571
TI  - Public conceptions of serious mental illness and substance abuse, their causes
      and treatments: findings from the 1996 general social survey.
AB  - OBJECTIVES: We examined the degree to which lay beliefs about the causes of
      disorders may predict beliefs about what constitutes appropriate treatment.
      METHODS: We analyzed randomized vignette data from the MacArthur Mental Health
      Module of the 1996 General Social Survey (n=1010). RESULTS: Beliefs in biological
      causes (i.e., chemical imbalance, genes) were significantly associated with the
      endorsement of professional, biologically focused treatments (e.g., prescription
      medication, psychiatrists, and mental hospital admissions). Belief that the way a
      person was raised was the cause of a condition was the only nonbiologically based
      causal belief associated with any treatment recommendations (talking to a clergy
      member). CONCLUSIONS: Lay beliefs about the biological versus nonbiological
      causes of mental and substance abuse disorders are related to beliefs regarding
      appropriate treatment. We suggest areas for further research with regard to
      better understanding this relationship in an effort to construct effective
      messages promoting treatment for mental health and substance abuse disorders.

PMID- 17008572
TI  - Mild cognitive impairment in early life and mental health problems in adulthood.
AB  - OBJECTIVES: We assessed the extent to which borderline mental retardation and
      mental retardation at preschool ages are related to emotional and behavioral
      problems in young adulthood. We also explored early risk factors for having
      mental health problems as a young adult that might be related to preschool
      differences in cognitive ability. METHODS: We used data from a cohort of births
      studied in the Johns Hopkins Collaborative Perinatal Study and followed up in the
      Pathways to Adulthood Study. Preschool cognitive functioning was assessed at 4
      years of age. Individual characteristics, psychosocial factors, and mental
      problems were prospectively evaluated from birth through young adulthood.
      RESULTS: Children with subaverage cognitive abilities were more likely to develop
      mental health problems than their counterparts with IQs above 80. Inadequate
      family interactions were shown to increase 2- to 4-fold the risk of emotional or
      behavioral problems among children with borderline mental retardation.
      CONCLUSIONS: Subaverage cognitive functioning in early life increases later risk
      of mental health problems. Future research may help to delineate possible
      impediments faced at different developmental stages and guide changes in
      supportive services to better address the needs of children with borderline
      mental retardation.

PMID- 17008573
TI  - Trends in Mental Health and Substance Abuse Services at the Nation's Community
      Health Centers: 1998-2003.
AB  - OBJECTIVE: We examined trends in delivery of mental health and substance abuse
      services at the nation's community health centers. METHODS: Analyses used data
      from the Health Resources and Services Administration (HRSA), Bureau of Primary
      Care's (BPHC) 1998 and 2003 Uniform Data System, merged with county-level data.
      RESULTS: Between 1998 and 2003, the number of patients diagnosed with a mental
      health/substance abuse disorder in community health centers increased from
      210,000 to 800,000. There was an increase in the number of patients per specialty
      mental health/substance abuse treatment provider and a decline in the mean number
      of patient visits, from 7.3 visits per patient to 3.5 by 2003. Although most
      community health centers had some on-site mental health/substance abuse services,
      centers without on-site services were more likely to be located in counties with
      fewer mental health/substance abuse clinicians, psychiatric emergency rooms, and
      inpatient hospitals. CONCLUSIONS: Community health centers are playing an
      increasingly central role in providing mental health/substance abuse treatment
      services in the United States. It is critical both to ensure that these centers
      have adequate resources for providing mental health/substance abuse care and that
      they develop effective linkages with mental health/substance abuse clinicians in
      the communities they serve.

PMID- 17008574
TI  - Detection of co-occurring mental illness among adult patients in the New Jersey
      substance abuse treatment system.
AB  - OBJECTIVES: We assessed the detection of mental illness in an adult population of
      substance abuse patients and the rate of referral for mental health treatment.
      METHODS: We obtained combined administrative records from 1994 to 1997 provided
      by the New Jersey substance abuse and mental health systems and estimated
      detection and referral rates of patients with co-occurring disorders (n =
      47,379). Mental illness was considered detected if a diagnosis was in the record
      and considered undetected if a diagnosis was not in the record but the patient
      was seen in both treatment systems within the same 12-month period. Predictors of
      detection and referral were identified. RESULTS: The detection rate of co
      occurring mental illness was 21.9% (n=10364); 57.9% (n=6001) of these individuals
      were referred for mental health treatment. Methadone maintenance clinics had the
      lowest detection rate but the highest referral rate. Male, Hispanic, and African
      American patients, as well as those who used heroin or were in the criminal
      justice system, had a higher risk of mental illness not being detected. Once
      detected, African American patients, heroin users, and patients in the criminal
      justice system were less likely to be referred for treatment. CONCLUSIONS: There
      is a need to improve the detection of mental illness among substance abuse
      patients and to provide integrated treatment.

PMID- 17008575
TI  - Characteristics of black and white suicide decedents in Fulton County, Georgia,
      1988-2002.
AB  - OBJECTIVES: We compared the prevalence of risk factors for Black and White
      suicide decedents in Fulton County, Georgia, from 1988-2002. METHODS: We used
      data from the Fulton County Medical Examiner's Office to compile information on
      suicides that occurred in Fulton County between 1988 and 2002. We used the chi2
      test and logistic regression to identify associations between suicide risk
      factors and race. RESULTS: Black suicide decedents were more likely than White
      suicide decedents to be male (odds ratio [OR]=2.06; 95% confidence interval
      [CI]=1.38, 3.09), to be younger, (< or =24 y [OR = 4.74; 95% CI = 2.88, 7.81]; 25
      34 y [OR = 2.79; 95% CI = 1.74, 4.47]; 35-44 y [OR = 1.86; 95% CI = 1.13, 3.07]),
      and to hurt others in a suicide (OR = 4.22; 95% CI = 1.60, 11.15) but less likely
      to report depression (OR=0.63; 95% CI=0.48, 0.83), to have a family history of
      suicide (OR=0.08; 95% CI=0.01, 0.61), or to leave a suicide note (OR=0.37; 95%
      CI=0.26, 0.52). CONCLUSIONS: Future research should consider that Black suicide
      decedents are less likely to report depression than White suicide decedents. This
      suicide risk difference is important when developing effective suicide prevention
      programs.

PMID- 17008576
TI  - Persistent tobacco use during pregnancy and the likelihood of psychiatric
      disorders.
AB  - OBJECTIVES: We examined the association between psychiatric disorders and tobacco
      use during pregnancy. METHODS: Data were derived from a population-based cohort
      of 744 pregnant African American and White low-income women living in urban and
      rural areas. The Diagnostic Interview Schedule was used to assess women for 20
      different psychiatric disorders. RESULTS: In comparison with nonusers, persistent
      tobacco users (women who had used tobacco after confirmation of their pregnancy)
      and nonpersistent users (women who had used tobacco but not after pregnancy
      confirmation) were 2.5 and 2 times as likely to have a psychiatric disorder.
      Twenty-five percent of persistent users had at least 1 of the following
      diagnoses: generalized anxiety disorder, bipolar I disorder, oppositional
      disorder, drug abuse or dependence, and attention deficit-hyperactivity disorder.
      CONCLUSIONS: In this cohort study, 5 diagnoses were more prevalent among
      persistent tobacco users than among nonusers, suggesting that several psychiatric
      disorders contribute to difficulty discontinuing tobacco use during pregnancy.
      Smoking cessation efforts focusing on pregnant women may need to address co
      occurring psychiatric disorders if they are to be successful.

PMID- 17008577
TI  - Treatment for cigarette smoking among depressed mental health outpatients: a
      randomized clinical trial.
AB  - OBJECTIVES: Using a brief contact control, we tested the efficacy of a staged
      care intervention to reduce cigarette smoking among psychiatric patients in
      outpatient treatment for depression. METHODS: We conducted a randomized clinical
      trial that included assessments at baseline and at months 3, 6, 12, and 18. Three
      hundred twenty-two patients in mental health outpatient treatment who were
      diagnosed with depression and smoked > or =1 cigarette per day participated. The
      desire to quit smoking was not a prerequisite for participation. Staged care
      intervention participants received computerized motivational feedback at baseline
      and at 3, 6, and 12 months and were offered a 6-session psychological counseling
      and pharmacological cessation treatment program. Brief contact control
      participants received a self-help guide and referral list of local smoking
      treatment providers. RESULTS: As we hypothesized, abstinence rates among staged
      care intervention participants exceeded those of brief contact control
      participants at months 12 and 18. Significant differences favoring staged care
      intervention also were found in occurrence of a quit attempt and stringency of
      abstinence goal. CONCLUSION: The data suggest that individuals in psychiatric
      treatment for depression can be aided in quitting smoking through use of staged
      care interventions and that smoking cessation interventions used in the general
      population can be implemented in psychiatric outpatient settings.

PMID- 17008578
TI  - Consumption of soft drinks and hyperactivity, mental distress, and conduct
      problems among adolescents in Oslo, Norway.
AB  - OBJECTIVES: We examined whether high levels of consumption of sugar-containing
      soft drinks were associated with mental distress, hyperactivity, and conduct
      problems among adolescents. METHODS: A cross-sectional population-based survey
      was conducted with 10th-grade students in Oslo, Norway (n = 5498). We used the
      Hopkins Symptom Checklist and the Strengths and Difficulties Questionnaire to
      assess mental health outcomes. RESULTS: There was a J-shaped dose-response
      relationship between soft drink consumption and mental distress, conduct
      problems, and total mental health difficulties score; that is, adolescents who
      did not consume soft drinks had higher scores (indicating worse symptoms) than
      those who consumed soft drinks at moderate levels but lower scores than those
      with high consumption levels. The relationship was linear for hyperactivity. In a
      logistic regression model, the association between soft drink consumption and
      mental health problems remained significant after adjustment for behavioral,
      social, and food-related variables. The highest adjusted odds ratios were
      observed for conduct problems among boys and girls who consumed 4 or more glasses
      of sugar-containing soft drinks per day. CONCLUSIONS: High consumption levels of
      sugar-containing soft drinks were associated with mental health problems among
      adolescents even after adjustment for possible confounders.

PMID- 17008579
TI  - Self-reported discrimination and mental health status among African descendants,
      Mexican Americans, and other Latinos in the New Hampshire REACH 2010 Initiative:
      the added dimension of immigration.
AB  - OBJECTIVES: We examined whether self-reported racial discrimination was
      associated with mental health status and whether this association varied with
      race/ethnicity or immigration status. METHODS: We performed secondary analysis of
      a community intervention conducted in 2002 and 2003 for the New Hampshire Racial
      and Ethnic Approaches to Community Health 2010 Initiative, surveying African
      descendants, Mexican Americans, and other Latinos. We assessed mental health
      status with the Mental Component Summary (MCS12) of the Medical Outcomes Study
      Short Form 12, and measured discrimination with questions related to respondents'
      ability to achieve goals, discomfort/anger at treatment by others, and access to
      quality health care. RESULTS: Self-reported discrimination was associated with a
      lower MCS12 score. Additionally, the strength of the association between self
      reported health care discrimination and lower MCS12 score was strongest for
      African descendants, then Mexican Americans, then other Latinos. These patterns
      may be explained by differences in how long a respondent has lived in the United
      States. Furthermore, the association of health care discrimination with lower
      MCS12 was weaker for recent immigrants. CONCLUSIONS: Discrimination may be an
      important predictor of poor mental health status among Black and Latino
      immigrants. Previous findings of decreasing mental health status as immigrants
      acculturate might partly be related to experiences with racial discrimination.

PMID- 17008580
TI  - Rates and correlates of seeking mental health services among Cambodian refugees.
AB  - OBJECTIVES: We assessed the rates and correlates of seeking mental health
      services among a probability sample of Cambodian refugees who needed such
      services. METHODS: Interviewers conducted face-to-face interviews with a
      representative sample drawn from the largest US community of Cambodian refugees.
      The analytic sample included 339 persons who met past 12-month criteria for
      posttraumatic stress disorder, major depression disorder, or alcohol use
      disorder. Respondents described contact with service providers for psychological
      problems during the preceding 12 months. We examined bivariate and multivariate
      predictors of seeking services. RESULTS: Respondents reported high rates of
      contact with both medical care providers (70%) and mental health care providers
      (46%). Seeking services from both types of providers was associated with lack of
      English-speaking proficiency, unemployment, 3 or fewer years of preimmigration
      education, and being retired or disabled. Women, individuals with health
      insurance, and persons receiving government assistance also were more likely to
      seek services. CONCLUSIONS: Cambodian refugees with mental health problems had
      high rates of seeking service for psychological problems during the preceding 12
      months. Research is needed to examine the effectiveness of services received by
      Cambodian refugees.

PMID- 17008581
TI  - Childhood trauma and women's health outcomes in a California prison population.
AB  - OBJECTIVES: We sought to describe the prevalence of childhood traumatic events
      among incarcerated women in substance abuse treatment and to assess the relation
      between cumulative childhood traumatic events and adult physical and mental
      health problems. METHODS: The study was modeled after the Adverse Childhood
      Events study's findings. In-depth baseline interview data for 500 women
      participating in the Female Offender Treatment and Employment Program evaluation
      were analyzed. RESULTS: Hypotheses were supported, and regression results showed
      that the impact of childhood traumatic events on health outcomes is strong and
      cumulative (greater exposure to childhood traumatic events increased the
      likelihood of 12 of 18 health-related outcomes, ranging from a 15% increase in
      the odds of reporting fair/poor health to a 40% increase in the odds of mental
      health treatment in adulthood). CONCLUSIONS: Our findings suggest a need for
      early prevention and intervention, and appropriate trauma treatment, within
      correctional treatment settings.

PMID- 17008583
TI  - Relative efficacy of a multisession sexual risk-reduction intervention for young
      men released from prisons in 4 states.
AB  - OBJECTIVES: We compared the effects of an enhanced multisession intervention with
      a single-session intervention on the sexual risk behavior of young men released
      from prison. METHODS: Young men, aged 18 to 29 years, were recruited from US
      prisons in 4 states and systematically assigned to the prerelease single-session
      intervention or the pre- and postrelease enhanced intervention. Both
      interventions addressed HIV, hepatitis, and other sexually transmitted
      infections; the enhanced intervention also addressed community reentry needs
      (e.g., housing, employment). Assessment data were collected before intervention,
      and 1, 12, and 24 weeks after release. RESULTS: A total of 522 men were included
      in intent-to-treat analyses. Follow-up rates ranged from 76% to 87%. Unprotected
      vaginal or anal sex during the 90 days before incarceration was reported by 86%
      of men in the enhanced intervention and 89% in the single-session intervention
      (OR=0.78; 95% CI=0.46, 1.32). At 24 weeks, 68% of men assigned to the enhanced
      intervention reported unprotected vaginal or anal sex compared with 78% of those
      assigned to the single-session intervention (OR=0.40; 95% CI=0.18, 0.88).
      CONCLUSION: Project START demonstrated the efficacy of a sexual risk-reduction
      intervention that bridges incarceration and community reentry.

PMID- 17008582
TI  - Concordance between self-reported maltreatment and court records of abuse or
      neglect among high-risk youths.
AB  - OBJECTIVES: We examined the concordance between measures of self-reported
      maltreatment and court records of abuse or neglect in a sample of detained
      youths. METHODS: Data were collected by the Northwestern Juvenile Project and
      include interviews from 1829 youths aged 10-18 years. Participants were newly
      detained youths in the Cook County Juvenile Temporary Detention Center in
      Illinois between 1995 and 1998. Self-reported cases of child maltreatment were
      compared with court records of abuse or neglect in the Cook County judicial
      system. RESULTS: We found that among detained youths, 16.6% of those who reported
      any maltreatment, 22.2% of those who reported the highest level of maltreatment,
      and 25.1% of those who reported that they required medical treatment as a result
      of maltreatment had a court record of abuse or neglect. Among those with any self
      reported maltreatment, girls (vs boys) and African Americans (vs Whites) were
      more likely to have a court record (adjusted odds ratio [AOR]=2.18; 95%
      confidence interval [CI]=1.53, 3.09; and AOR=2.12; 95% CI=1.23, 3.63,
      respectively). CONCLUSIONS: Official records seriously underestimate the
      prevalence of maltreatment, which indicates that multiple data sources are needed
      to document the true prevalence of maltreatment.

PMID- 17008584
TI  - Chlamydia trachomatis and Neisseria gonorrhoeae infections among men and women
      entering California prisons.
AB  - OBJECTIVE: We estimated the prevalence of Chlamydia trachomatis and Neisseria
      gonorrhoeae infection among newly arriving inmates at 6 California prisons.
      METHODS: In this cross-sectional study in 1999, urine specimens collected from
      698 men aged 18 to 25 years and 572 women aged 18 years or older were tested at
      intake for C trachomatis and N gonorrhoeae using ligase chain reaction. An
      analysis of demographic and arrest-related correlates of C trachomatis and N
      gonorrhoeae infection was performed. RESULTS: The overall C trachomatis
      prevalence was 9.9% (95% CI=7.8%, 12.3%) among men aged 18 to 25 years, 8.9% (95%
      CI = 2.9%, 22.1%) among women aged 18 to 25 years, and 3.3% (95% CI=2.0%, 5.1%)
      among women overall. Three N gonorrhoeae cases were detected with an overall
      prevalence of 0.24% (95% CI=0.05%, 0.69%). CONCLUSIONS: The prevalence of C
      trachomatis infection at entry to California prisons, especially among young
      female and male inmates, was high, which supports routine screening at entry into
      prison. In addition, screening in a jail setting where most detainees are
      incarcerated before entry into the prison setting may provide an excellent
      earlier opportunity to identify these infections and treat disease to prevent
      complications and burden of infection in this high-risk population.

PMID- 17008585
TI  - Employee and customer injury during violent crimes in retail and service
      businesses.
AB  - OBJECTIVES: We sought to compare the frequency and risk factors for employees and
      customers injured during crimes in retail (convenience, grocery, and liquor
      stores) and service businesses (bars, restaurants, motels). METHODS: A total of
      827 retail and service businesses in Los Angeles were randomly selected. Police
      crime reports (n=2029) from violent crimes that occurred in these businesses from
      January 1996 through June 2001 were individually reviewed to determine whether a
      customer or an employee was injured and to collect study variables. RESULTS: A
      customer injury was 31% more likely (95% confidence interval [CI]=1.11, 1.51)
      than an employee injury during a violent crime. Customer injury was more frequent
      than employee injury during violent crimes in bars, restaurants, convenience
      stores, and motels but less likely in grocery or liquor stores. Injury risk was
      increased for both employees and customers when resisting the perpetrator and
      when the perpetrator was suspected of using alcohol. Customers had an increased
      risk for injury during crimes that occurred outside (relative risk [RR]=2.01; 95%
      CI=1.57, 2.58) and at night (RR=1.79; 95% CI=1.40, 2.29). CONCLUSIONS: Security
      programs should be designed to protect customers as well as employees.

PMID- 17008586
TI  - The RXR agonist bexarotene improves cholesterol homeostasis and inhibits
      atherosclerosis progression in a mouse model of mixed dyslipidemia.
AB  - OBJECTIVE: The activity of the antitumoral agent bexarotene (Targretin,
      Bexarotene) depends on its binding to the nuclear retinoid-X receptor (RXR) and
      subsequent transcriptional regulation of target genes. Through RXR activation,
      bexarotene may modulate numerous metabolic pathways involved in atherosclerosis.
      Here, we investigated the effect of bexarotene on atherosclerosis progression in
      a dyslipidemic murine model, the human apolipoprotein E2 knockin mouse, that
      develops essentially macrophage-laden lesions. METHODS AND RESULTS:
      Atherosclerotic lesions together with different metabolic pathways involved in
      atherosclerosis were investigated in mice treated or not with bexarotene.
      Bexarotene protects from atherosclerosis development in mice, at least in part by
      improving the circulating cholesterol distribution profile likely via a marked
      decrease of dietary cholesterol absorption caused by modulation of intestinal
      expression of genes recently identified as major players in this process, Niemann
      Pick-C1-Like1 (NPC1L1) and CD13. This atheroprotection appears despite a strong
      hypertriglyceridemia. Moreover, bexarotene treatment only modestly modulates
      inflammatory gene expression in the vascular wall, but markedly enhanced the
      capacity of macrophages to efflux cellular lipids. CONCLUSIONS: These data
      provide evidence of a favorable pharmacological effect of bexarotene on
      atherosclerosis despite the induction of hypertriglyceridemia, likely via a
      beneficial action on intestinal absorption and macrophage efflux.

PMID- 17008587
TI  - Increased concentrations of C-reactive protein and IL-6 but not IL-18 are
      independently associated with incident coronary events in middle-aged men and
      women: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002.
AB  - OBJECTIVE: We performed a prospective case-cohort study in initially healthy,
      middle-aged men and women from the MONICA/KORA Augsburg studies conducted between
      1984 and 2002 to assess the role of IL-18 in comparison with IL-6 and CRP in the
      prediction of incident coronary heart disease (CHD). METHODS AND RESULTS:
      Concentrations of IL-18 were measured in 382 case subjects with incident CHD and
      1980 noncases. Mean follow-up was 11 years. Baseline concentrations of IL-18 were
      slightly higher in cases than in noncases (172.4 [1.0] versus 161.3 [1.0] pg/mL,
      respectively; P=0.114), but were clearly elevated for C-reactive protein (CRP)
      and IL-6 in cases compared with noncases. In multivariable analyses, accounting
      for classical cardiovascular risk factors and inflammatory markers, no
      statistically significant association was seen between increased concentrations
      of IL-18 and incident CHD both in men (hazard ratio [HR] and 95% confidence
      intervals [CIs] comparing extreme tertiles, 1.20; 95% CI, 0.85 to 1.69), and in
      women (HR, 1.25; 95% CI, 0.67 to 2.34). However, in this population increased
      concentrations of CRP and IL-6 were found to be independent predictors of future
      CHD events, even after multivariable adjustment. CONCLUSIONS: Elevated
      concentrations of CRP and IL-6, but not IL-18, were independently associated with
      risk of CHD in subjects from an area with moderate absolute risk.

PMID- 17008588
TI  - Cholesterol 7alpha-hydroxylase deficiency in mice on an APOE*3-Leiden background
      increases hepatic ABCA1 mRNA expression and HDL-cholesterol.
AB  - OBJECTIVE: High-density lipoprotein (HDL) plays a key role in protection against
      development of atherosclerosis by reducing inflammation, protecting against LDL
      oxidation, and promoting reverse cholesterol transport from peripheral tissues to
      the liver for secretion into bile. Cholesterol 7alpha-hydroxylase (Cyp7a1)
      catalyzes the rate-limiting step in the intrahepatic conversion of cholesterol to
      bile acids that may have a role in HDL metabolism. We investigated the effect of
      Cyp7a1 deficiency on HDL metabolism in APOE*3-Leiden transgenic mice. METHODS AND
      RESULTS: Reduced bile acid biosynthesis in Cyp7a1-/-.APOE*3-Leiden mice versus
      APOE*3-Leiden mice did not affect total plasma cholesterol levels, but the
      distribution of cholesterol over various lipoproteins was different. Cholesterol
      was decreased in apoB-containing lipoproteins (ie, VLDL and IDL/LDL), whereas
      cholesterol was increased in HDL. The activity of PLTP and LCAT, which play a
      role in HDL catabolism, were not changed, and neither was HDL clearance. However,
      the hepatic cholesterol content was 2-fold increased, which was accompanied by a
      2-fold elevated expression of hepatic ABCA1 and increased rate of cholesterol
      efflux from the liver to HDL. CONCLUSIONS: Strongly reduced bile acid synthesis
      in Cyp7a1-/-.APOE*3-Leiden mice leads to increased plasma HDL-cholesterol levels,
      as related to an increased hepatic expression of ABCA1.

PMID- 17008589
TI  - Endotoxin induces toll-like receptor 4 expression in vascular smooth muscle cells
      via NADPH oxidase activation and mitogen-activated protein kinase signaling
      pathways.
AB  - OBJECTIVE: Toll-like receptor 4 (TLR4) plays a major role mediating endotoxin
      induced cellular inflammation and regulates vascular smooth muscle cell (VSMC)
      proliferation, which is related to atherogenesis and restenosis. This study was
      conducted to investigate the mechanisms involved in lipopolysaccharide (LPS)
      induced TLR4 expression in VSMCs. METHODS AND RESULTS: Stimulation of human
      aortic smooth muscle cells (HASMCs) with LPS significantly increased TLR4
      expression. The increase was regulated by nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase (including the activation of subunits p47(phox) and
      Rac1), which mediates the production of reactive oxygen species and the
      activation of intracellular mitogen-activated protein kinase signaling pathways.
      Treatment with polyethylene-glycol-conjugated superoxide dismutase, N
      acetylcysteine (NAC), diphenylene iodonium (DPI), or apocynin significantly
      decreased LPS-induced TLR4 expression. An actinomycin D chase experiment showed
      that LPS increased the half-life of TLR4 mRNA. Inhibition of NADPH oxidase
      activity by DPI, apocynin, or NAC significantly decreased TLR4 mRNA stability, as
      did the knock-down of RAC1 gene expression by RNA interference. We also
      demonstrated in an animal model that LPS administration led to a significant
      elevation of balloon-injury-induced neointimal hyperplasia, and of TLR4
      expression, in rabbit aorta. CONCLUSIONS: These findings suggest that NADPH
      oxidase activation, mRNA stabilization, and MAPK signaling pathways play critical
      roles in LPS-enhanced TLR4 expression in HASMCs, which contributes to vascular
      inflammation and cardiovascular disorders.

PMID- 17008590
TI  - Tissue factor and coagulation factor VII levels during acute myocardial
      infarction: association with genotype and adverse events.
AB  - OBJECTIVE: We investigated in patients with ongoing myocardial infarction (MI)
      whether coagulation factor VII (FVII) and tissue factor (TF) levels are affected
      at admission by genetic components and whether they may predict subsequent
      cardiovascular events. METHODS AND RESULTS: 256 patients admitted for MI were
      evaluated for FVII and TF antigen levels before any treatment at entry, and were
      genotyped for FVII and TF polymorphisms. FVII gene insertions at -323, 11293 and
      the -402G/A change predicted FVII levels and explained 14% of variance. The -603
      TF gene polymorphism failed to affect significantly TF levels (P=0.07). These
      variables were correlated with the incidence of death (36 patients) and
      reinfarction (9 patients) after a median follow-up of 397 days. Events were
      independently predicted by FVII (HR 2.1, 95% CI 1.2 to 5.7) and TF (HR 4.1, 95%
      CI 2 to 11) levels. Composite end point was significantly worse when both
      parameters were above the receiver-operating characteristics (ROC) values (HR
      8.3, 95% CI 5 to 18, compared with FVII and TF below), and above the ROC value of
      TF (>630 pg/mL) it differed among FVII genotype groups. CONCLUSIONS: Admission
      FVII and TF antigen levels, partially predicted by polymorphisms, are independent
      predictors of mortality and reinfarction in patients with acute MI.

PMID- 17008591
TI  - Asp92Asn polymorphism in the myeloid IgA Fc receptor is associated with
      myocardial infarction in two disparate populations: CARE and WOSCOPS.
AB  - OBJECTIVE: Statins reduce inflammation and risk of myocardial infarction (MI).
      Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we
      hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI
      and that this risk would be modified by pravastatin. METHODS AND RESULTS: In the
      placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers
      of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI
      1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12%
      in noncarriers (P(interaction)=0.007). In the placebo arm of the all-male West of
      Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio
      for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for
      pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55
      (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers
      (P(interaction)=0.55). CONCLUSIONS: Carriers of 92Asn had increased risk of MI in
      CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk
      in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was
      observed in CARE but not in WOSCOPS.

PMID- 17008592
TI  - Histone deacetylase inhibitor reduces monocyte adhesion to endothelium through
      the suppression of vascular cell adhesion molecule-1 expression.
AB  - OBJECTIVE: Tumor necrosis factor (TNF)-alpha initiates numerous changes in
      endothelial cell (EC) gene expression that contributes to the pathology of
      various diseases including inflammation. We hypothesized that TNF-alpha-mediated
      gene induction involves multiple signaling pathways, and that inhibition of one
      or more of these pathways may selectively target subsets of TNF-alpha-responsive
      genes and functions. METHODS AND RESULTS: Human umbilical vein endothelial cells
      (ECs) were preincubated with inhibitors of PI3 kinase (LY294002), histone
      deacetylases (HDAC) (trichostatin A [TSA]), de novo protein synthesis (CHX),
      proteasome (MG-132), and GATA factors (K-11430) before exposure to TNF-alpha at 4
      hours and analyzed by microarray. TNF-alpha-mediated induction of vascular cell
      adhesion molecule-1 (VCAM-1) was attenuated by all of these inhibitors, whereas
      in contrast, stimulation of intercellular adhesion molecule-1 (ICAM-1) was
      blocked by MG-132 alone. Moreover TSA blocked TNF-alpha-mediated induction of
      monocyte adhesion both in vitro and in vivo through the suppression of VCAM-1.
      Further analysis demonstrated that HDAC3 plays a significant role in the
      regulation of TNF-alpha-mediated VCAM-1 expression. CONCLUSIONS: TNF-alpha
      activates ECs via multiple signaling pathways, and these pathways may be
      selectively targeted to modulate EC function. Moreover, TSA treatment reduced
      monocyte adhesion via VCAM-1 suppression in vitro and in vivo, suggesting that
      TSA might be useful for the attenuation of the inflammatory response in EC.

PMID- 17008593
TI  - Smooth muscle cells in atherosclerosis originate from the local vessel wall and
      not circulating progenitor cells in ApoE knockout mice.
AB  - OBJECTIVE: Recent studies of bone marrow (BM)-transplanted apoE knockout (apoE-/
      ) mice have concluded that a substantial fraction of smooth muscle cells (SMCs)
      in atherosclerosis arise from circulating progenitor cells of hematopoietic
      origin. This pathway, however, remains controversial. In the present study, we
      reexamined the origin of plaque SMCs in apoE-/- mice by a series of BM
      transplantations and in a novel model of atherosclerosis induced in surgically
      transferred arterial segments. METHODS AND RESULTS: We analyzed plaques in
      lethally irradiated apoE-/- mice reconstituted with sex-mismatched BM cells from
      eGFP+ apoE-/- mice, which ubiquitously express enhanced green fluorescent protein
      (eGFP), but did not find a single SMC of donor BM origin among approximately
      10,000 SMC profiles analyzed. We then transplanted arterial segments between
      eGFP+ apoE-/- and apoE-/- mice (isotransplantation except for the eGFP transgene)
      and induced atherosclerosis focally within the graft by a recently invented
      collar technique. No eGFP+ SMCs were found in plaques that developed in apoE-/-
      artery segments grafted into eGFP+ apoE-/- mice. Concordantly, 96% of SMCs were
      eGFP+ in plaques induced in eGFP+ apoE-/- artery segments grafted into apoE-/-
      mice. CONCLUSIONS: These experiments show that SMCs in atherosclerotic plaques
      are exclusively derived from the local vessel wall in apoE-/- mice.

PMID- 17008594
TI  - Preconditioning enters the era of "physiological proteomics".

PMID- 17008595
TI  - Vascular endothelial growth factor signaling to endothelial nitric oxide
      synthase: more than a FLeeTing moment.

PMID- 17008596
TI  - Sphingosine-1-phosphate: waging a battle in the diabetic blood vessel.

PMID- 17008597
TI  - Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms.
AB  - Chronic hypoxic exposure induces changes in the structure of pulmonary arteries,
      as well as in the biochemical and functional phenotypes of each of the vascular
      cell types, from the hilum of the lung to the most peripheral vessels in the
      alveolar wall. The magnitude and the specific profile of the changes depend on
      the species, sex, and the developmental stage at which the exposure to hypoxia
      occurred. Further, hypoxia-induced changes are site specific, such that the
      remodeling process in the large vessels differs from that in the smallest
      vessels. The cellular and molecular mechanisms vary and depend on the cellular
      composition of vessels at particular sites along the longitudinal axis of the
      pulmonary vasculature, as well as on local environmental factors. Each of the
      resident vascular cell types (ie, endothelial, smooth muscle, adventitial
      fibroblast) undergo site- and time-dependent alterations in proliferation, matrix
      protein production, expression of growth factors, cytokines, and receptors, and
      each resident cell type plays a specific role in the overall remodeling response.
      In addition, hypoxic exposure induces an inflammatory response within the vessel
      wall, and the recruited circulating progenitor cells contribute significantly to
      the structural remodeling and persistent vasoconstriction of the pulmonary
      circulation. The possibility exists that the lung or lung vessels also contain
      resident progenitor cells that participate in the remodeling process. Thus the
      hypoxia-induced remodeling of the pulmonary circulation is a highly complex
      process where numerous interactive events must be taken into account as we search
      for newer, more effective therapeutic interventions. This review provides
      perspectives on each of the aforementioned areas.

PMID- 17008598
TI  - Environmental cardiology: studying mechanistic links between pollution and heart
      disease.
AB  - Environmental factors are considered key determinants of cardiovascular disease.
      Although lifestyle choices such as smoking, diet, and exercise are viewed as
      major environmental influences, the contribution of pollutants and environmental
      chemicals is less clear. Accumulating evidence suggests that exposure to
      pollutants and chemicals could elevate the risk of cardiovascular disease. Many
      epidemiological studies report that exposure to fine particles present in ambient
      air is associated with an increase in cardiovascular mortality. Statistically
      significant relationships between particulate air pollution and ischemic heart
      disease, arrhythmias, and heart failure have been reported. Animal studies show
      that exposure to ambient air particles increases peripheral thrombosis and
      atherosclerotic lesion formation. Exposures to arsenic, lead, cadmium, pollutant
      gases, solvents, and pesticides have also been linked to increased incidence of
      cardiovascular disease. Mechanistically, these effects have been attributed to
      changes in the synthesis or reactivity of nitric oxide that may be caused by
      environmental oxidants or increased endogenous production of reactive oxygen
      species. Additional studies are urgently needed to: identify the contribution of
      individual pollutants to specific aspects of cardiovascular disease; establish
      causality; elucidate the underlying physiological and molecular mechanisms;
      estimate the relative susceptibility of diseased and healthy individuals and that
      of specific population groups; and determine whether pollutant exposure are risk
      correlates, that is, whether they influence major risk factors, such as
      hypertension, cholesterol, or diabetes, or whether they contribute to the
      absolute risk of heart disease. Collectively, these investigations could
      contribute to the emergent field of environmental cardiology.

PMID- 17008599
TI  - Membrane potential fluctuations resulting from submembrane Ca2+ releases in
      rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic
      depolarization that controls their chronotropic state.
AB  - Stochastic but roughly periodic LCRs (Local subsarcolemmal ryanodine receptor
      mediated Ca(2+) Releases) during the late phase of diastolic depolarization (DD)
      in rabbit sinoatrial nodal pacemaker cells (SANCs) generate an inward current
      (I(NCX)) via the Na(+)/Ca(2+) exchanger. Although LCR characteristics have been
      correlated with spontaneous beating, the specific link between LCR
      characteristics and SANC spontaneous beating rate, ie, impact of LCRs on the fine
      structure of the DD, have not been explicitly defined. Here we determined how
      LCRs and resultant I(NCX) impact on the DD fine structure to control the
      spontaneous SANC firing rate. Membrane potential (V(m)) recordings combined with
      confocal Ca(2+) measurements showed that LCRs impart a nonlinear, exponentially
      rising phase to the DD later part, which exhibited beat-to-beat V(m) fluctuations
      with an amplitude of approximately 2 mV. Maneuvers that altered LCR timing or
      amplitude of the nonlinear DD (ryanodine, BAPTA, nifedipine or isoproterenol)
      produced corresponding changes in V(m) fluctuations during the nonlinear DD
      component, and the V(m) fluctuation response evoked by these maneuvers was
      tightly correlated with the concurrent changes in spontaneous beating rate
      induced by these perturbations. Numerical modeling, using measured LCR
      characteristics under these perturbations, predicted a family of local I(NCX)
      that reproduced V(m) fluctuations measured experimentally and determined the
      onset and amplitude of the nonlinear DD component and the beating rate. Thus,
      beat-to-beat V(m) fluctuations during late DD phase reflect the underlying
      LCR/I(NCX) events, and the ensemble of these events forms the nonlinear DD
      component that ultimately controls the SANC chronotropic state in tight
      cooperation with surface membrane ion channels.

PMID- 17008600
TI  - Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in
      heart development and beta-adrenergic signaling.
AB  - G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate
      ligand-bound 7-transmembrane receptors, causing receptor uncoupling from G
      proteins and potentially activating non-G-protein signaling pathways. GRK2 is
      unique among members of the GRK family in that its genetic ablation causes
      embryonic lethality. Cardiac abnormalities in GRK2 null embryos implicated GRK2
      in cardiac development but prevented studies of the knockout phenotype in adult
      hearts. Here, we created GRK2-loxP-targeted mice and used Cre recombination to
      generate germline and cardiac-specific GRK2 knockouts. GRK2 deletion in the
      preimplantation embryo with EIIa-Cre (germline null) resulted in developmental
      retardation and embryonic lethality between embryonic day 10.5 (E10.5) and E11.5.
      At E9.5, cardiac myocyte specification and cardiac looping were normal, but
      ventricular development was delayed. Cardiomyocyte-specific ablation of GRK2 in
      the embryo with Nkx2.5-driven Cre (cardiac-specific GRK2 knockout) produced
      viable mice with normal heart structure, function, and cardiac gene expression.
      Cardiac-specific GRK2 knockout mice exhibited enhanced inotropic sensitivity to
      the beta-adrenergic receptor agonist isoproterenol, with impairment of normal
      inotropic and lusitropic tachyphylaxis, and exhibited accelerated development of
      catecholamine toxicity with chronic isoproterenol treatment. These findings show
      that cardiomyocyte autonomous GRK2 is not essential for myocardial development
      after cardiac specification, suggesting that embryonic developmental
      abnormalities may be attributable to extracardiac effects of GRK2 ablation. In
      the adult heart, cardiac GRK2 is a major factor regulating inotropic and
      lusitropic tachyphylaxis to beta-adrenergic agonist, which likely contributes to
      its protective effects in catecholamine cardiomyopathy.

PMID- 17008601
TI  - Increases in mitochondrial reactive oxygen species trigger hypoxia-induced
      calcium responses in pulmonary artery smooth muscle cells.
AB  - Mitochondria have been implicated as a potential site of O(2) sensing underlying
      hypoxic pulmonary vasoconstriction (HPV), but 2 disparate models have been
      proposed to explain their reaction to hypoxia. One model proposes that hypoxia
      induced increases in mitochondrial reactive oxygen species (ROS) generation
      activate HPV through an oxidant-signaling pathway, whereas the other proposes
      that HPV is a result of decreased oxidant signaling. In an attempt to resolve
      this debate, we use a novel, ratiometric, redox-sensitive fluorescence resonance
      energy transfer (HSP-FRET) probe, in concert with measurements of
      reduced/oxidized glutathione (GSH/GSSG), to assess cytosolic redox responses in
      cultured pulmonary artery smooth muscle cells (PASMCs). Superfusion of PASMCs
      with hypoxic media increases the HSP-FRET ratio and decreases GSH/GSSG,
      indicating an increase in oxidant stress. The antioxidants
      pyrrolidinedithiocarbamate and N-acetyl-l-cysteine attenuated this response, as
      well as the hypoxia-induced increases in cytosolic calcium ([Ca(2+)](i)),
      assessed by the Ca(2+)-sensitive FRET sensor YC2.3. Adenoviral overexpression of
      glutathione peroxidase or cytosolic or mitochondrial catalase attenuated the
      hypoxia-induced increase in ROS signaling and [Ca(2+)](i). Adenoviral
      overexpression of cytosolic Cu, Zn-superoxide dismutase (SOD-I) had no effect on
      the hypoxia-induced increase in ROS signaling and [Ca(2+)](i), whereas
      mitochondrial matrix-targeted Mn-SOD (SOD-II) augmented [Ca(2+)](i). The
      mitochondrial inhibitor myxothiazol attenuated the hypoxia-induced changes in the
      ROS signaling and [Ca(2+)](i), whereas cyanide augmented the increase in
      [Ca(2+)](i). Finally, simultaneous measurement of ROS and Ca(2+) signaling in the
      same cell revealed that the initial increase in these 2 signals could not be
      distinguished temporally. These results demonstrate that hypoxia triggers
      increases in PASMC [Ca(2+)](i) by augmenting ROS signaling from the mitochondria.

PMID- 17008602
TI  - Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines
      the noninflammatory and protective transcriptional response of macrophages to
      hemoglobin.
AB  - Heme toxicity contributes to the pathogenesis of chronic inflammatory diseases,
      atherosclerosis, and hemolysis associated vasculopathy. Macrophage clearance of
      cell free hemoglobin (Hb) is thus an essential homeostatic function of these
      cells. We examined the transcriptional response of human PBMC derived macrophages
      to Hb by gene array analysis. The observed noninflammatory macrophage response
      was characterized by induction of an antioxidative and antiinflammatory gene
      expression pattern with most prominent induction of the inducible heme oxygenase
      (HO-1). The metabolically active Hb-CD163-HO-1 pathway resulted in synthesis of
      ferritin-1 of the antioxidative and antiinflammatory end products linked to heme
      breakdown by HO-1. This response was mediated by the Hb scavenger receptor CD163
      and heme and was not related to Hb mediated depletion of reduced glutathione. In
      contrast to other cellular responses induced by CD163, there was no role of
      protein phosphorylation dependent CD163 signaling in the protective macrophage
      response to Hb. Instead, CD163 acted as an Hb transporter, which undergoes
      constitutive and ligand independent internalization and recycling between the
      cell surface and early endosomes. The expression of CD163 and HO-1 in macrophages
      of neovascularized atherosclerotic lesions suggests that the pathway described
      herein is active in vivo. Noninflammatory Hb clearance and intimately linked HO-1
      expression may provide the long sought-after explanation for the antiinflammatory
      activity associated with CD163-positive macrophages.

PMID- 17008603
TI  - Neuronal angiotensin II type 1 receptor upregulation in heart failure: activation
      of activator protein 1 and Jun N-terminal kinase.
AB  - Chronic heart failure (CHF) is a leading cause of mortality in developed
      countries. Angiotensin II (Ang II) plays an important role in the development and
      progression of CHF. Many of the important functions of Ang II are mediated by the
      Ang II type 1 receptor (AT(1)R), including the increase in sympathetic nerve
      activity in CHF. However, the central regulation of the AT(1)R in the setting of
      CHF is not well understood. This study investigated the AT(1)R in the rostral
      ventrolateral medulla (RVLM) of rabbits with CHF, its downstream pathway, and its
      gene regulation by the transcription factor activator protein 1 (AP-1). Studies
      were performed in 5 groups of rabbits: sham (n=5), pacing-induced (3 to 4 weeks)
      CHF (n=5), CHF with intracerebroventricular (ICV) losartan treatment (n=5),
      normal with ICV Ang II treatment (n=5), and normal with ICV Ang II plus losartan
      treatment (n=5). AT(1)R mRNA and protein expressions, plasma Ang II, and AP-1-DNA
      binding activity were significantly higher in RVLM of CHF compared with Sham
      rabbits (240.4+/-30.2%, P<0.01; 206.6+/-25.8%, P<0.01; 280+/-36.5%, P<0.05; 207+/
      16.4%, P<0.01, respectively). Analysis of the stress-activated protein kinase/Jun
      N-terminal kinase (SAPK/JNK) pathway showed that phosphorylated c-Jun proteins,
      phosphorylated JNK proteins, and JNK activity increased significantly in RVLM of
      CHF compared with sham (262.9+/-48.1%, 213.8+/-27.7%, 148.2+/-10.1% of control,
      respectively). Importantly, ICV losartan in CHF rabbits attenuated these
      increases. ICV Ang II in normal rabbits simulated the molecular changes seen in
      CHF. This effect was blocked by concomitant ICV losartan. In addition, Ang II
      induced AT(1)R expression was blocked by losartan and a JNK inhibitor, but not by
      extracellular signal-regulated kinase or p38 MAP kinase inhibitors in a neuronal
      cell culture. These data suggest that central Ang II activates the AT(1)R,
      SAPK/JNK pathway. AP-1 may further regulate gene expression in RVLM in the CHF
      state.

PMID- 17008604
TI  - Transient receptor potential vanilloid 4-mediated disruption of the alveolar
      septal barrier: a novel mechanism of acute lung injury.
AB  - Disruption of the alveolar septal barrier leads to acute lung injury, patchy
      alveolar flooding, and hypoxemia. Although calcium entry into endothelial cells
      is critical for loss of barrier integrity, the cation channels involved in this
      process have not been identified. We hypothesized that activation of the
      vanilloid transient receptor potential channel TRPV4 disrupts the alveolar septal
      barrier. Expression of TRPV4 was confirmed via immunohistochemistry in the
      alveolar septal wall in human, rat, and mouse lung. In isolated rat lung, the
      TRPV4 activators 4alpha-phorbol-12,13-didecanoate and 5,6- or 14,15
      epoxyeicosatrienoic acid, as well as thapsigargin, a known activator of calcium
      entry via store-operated channels, all increased lung endothelial permeability as
      assessed by measurement of the filtration coefficient, in a dose- and calcium
      entry dependent manner. The TRPV antagonist ruthenium red blocked the
      permeability response to the TRPV4 agonists, but not to thapsigargin. Light and
      electron microscopy of rat and mouse lung revealed that TRPV4 agonists
      preferentially produced blebs or breaks in the endothelial and epithelial layers
      of the alveolar septal wall, whereas thapsigargin disrupted interendothelial
      junctions in extraalveolar vessels. The permeability response to 4alpha-phorbol
      12,13-didecanoate was absent in TRPV4(-/-) mice, whereas the response to
      thapsigargin remained unchanged. Collectively, these findings implicate TRPV4 in
      disruption of the alveolar septal barrier and suggest its participation in the
      pathogenesis of acute lung injury.

PMID- 17008605
TI  - Oxidized low-density lipoprotein-dependent endothelial arginase II activation
      contributes to impaired nitric oxide signaling.
AB  - Oxidized low-density lipoprotein (OxLDL) impairs NO signaling and endothelial
      function, and contributes to the pathogenesis of atherosclerosis. Arginase
      reciprocally regulates NO levels in endothelial cells by competing with NO
      synthase for the substrate l-arginine. In human aortic endothelial cells, OxLDL
      stimulation increased arginase enzyme activity in a time- and dose-dependent
      manner. Arginase activity reached its maximum as early as 5 minutes, was
      maintained for a period of more than 48 hours, and was associated with a
      reciprocal decrease in NO metabolite (NOx [nitrite and nitrate]) production.
      Furthermore, OxLDL induced arginase II mRNA expression after 4 hours. Small
      interfering RNA targeted to arginase II decreased both the quantity and the
      activity of arginase from baseline, prevented OxLDL-dependent increases in
      arginase activity, and induced an increase in NOx production. Immunofluorescence
      analysis revealed an association of arginase II with the microtubule
      cytoskeleton. Microtubule disruption with nocodazole caused a dramatic
      redistribution of arginase II to a diffuse cytosolic pattern, increased arginase
      activity, and decreased NOx production, which was restored in the presence of the
      specific arginase inhibitor (S)-(2-boronoethyl)-l-cysteine (BEC). On the other
      hand, epothilone B prevented microtubule disruption and inhibited OxLDL-dependent
      increases in arginase activity and attenuated OxLDL-dependent decreases in NOx.
      Preincubation of rat aortic rings with OxLDL resulted in an increase in arginase
      activity and a decrease in NOx production. This was reversed by arginase
      inhibition with the BEC. Thus, OxLDLs increase arginase activity by a sequence of
      regulatory events that involve early activation through decreased association
      with microtubules and a later increase in transcription. Furthermore, increased
      arginase activity contributes to OxLDL-dependent impairment of NOx production.
      Arginase, therefore, represents a novel target for therapy in atherosclerosis.

PMID- 17008607
TI  - Cost-effectiveness of recombinant activated factor VII in the treatment of
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is among the most costly
      and debilitating forms of stroke. Results from a recent Phase IIb clinical trial
      demonstrate that administration of recombinant activated factor VII (rFVIIa)
      reduces ICH mortality and improves functional outcome. In the current analysis,
      we examine the cost-effectiveness of early treatment with rFVIIa for ICH in the
      United States. METHODS: A decision-analytic model was developed to estimate the
      lifetime costs and outcomes associated with rFVIIa treatment at doses of 40, 80
      and 160 microg/kg compared with current standard of care in treating ICH, from a
      US third-party payer perspective. The patient population was similar to that of
      the Phase IIb clinical trial. Model structure and inputs were obtained from
      published literature, clinical trial data, claims databases, and expert opinion.
      All costs are presented in 2005 US dollars. Outcomes included incremental cost
      per life-year (LY) saved and incremental cost per quality-adjusted life-year
      (QALY) gained. Costs and outcomes were discounted at 3% annually. Univariate and
      multivariate sensitivity analyses were conducted to assess model robustness.
      RESULTS: Compared with standard care, treatment with rFVIIa 40 microg/kg, and 160
      microg/kg results in total lifetime cost-effectiveness ratios of 6308
      dollars/QALY and 3152 dollars/QALY, respectively. Treatment with rFVIIa 80
      microg/kg was found to be cost saving and a gain of 1.67 QALYs is achieved over a
      patient's lifetime. These results are robust to changes in input parameters.
      CONCLUSIONS: Treatment of ICH with rFVIIa 40 microg/kg and 160 microg/kg appears
      to be cost-effective (<or=50,000 dollars/QALY). At the 80 microg/kg dose, rFVIIa
      was not only cost-effective, but also cost saving.

PMID- 17008606
TI  - Heparin-II domain of fibronectin is a vascular endothelial growth factor-binding
      domain: enhancement of VEGF biological activity by a singular growth
      factor/matrix protein synergism.
AB  - We describe extracellular interactions between fibronectin (Fn) and vascular
      endothelial growth factor (VEGF) that influence integrin-growth factor receptor
      crosstalk and cellular responses. In previous work, we found that VEGF bound
      specifically to fibronectin (Fn) but not vitronectin or collagens. Herein we
      report that VEGF binds to the heparin-II domain of Fn and that the cell-binding
      and VEGF-binding domains of Fn, when physically linked, are necessary and
      sufficient to promote VEGF-induced endothelial cell proliferation, migration, and
      Erk activation. Using recombinant Fn domains, the C-terminal heparin-II domain of
      Fn (type III repeats 13 to 14) was identified as a key VEGF-binding site.
      Mutation of the heparin-binding residues on FnIII(13-14) abolished VEGF binding,
      and peptides corresponding to the heparin-binding sequences in FnIII(13-14)
      inhibited VEGF binding to Fn. Fn fragments containing both the alpha5beta1
      integrin-binding domain (III 9 to 10) and the VEGF-binding domain (III 13 to 14)
      significantly enhanced VEGF-induced EC migration and proliferation and induced
      strong phosphorylation of the VEGF receptor and Erk. Neither the cell-binding or
      VEGF-binding fragment of Fn alone had comparable VEGF-promoting effects. These
      results suggest that the mechanism of VEGF/Fn synergism is mediated
      extracellularly by the formation of a novel VEGF/Fn complex requiring both the
      cell-binding and VEGF-binding domains linked in a single molecular unit. These
      data also highlight a new function for the Fn C-terminal heparin-binding domain
      that may have important implications for angiogenesis and tumor growth.

PMID- 17008608
TI  - Modulation of dilator responses of cerebral arterioles by extracellular
      superoxide dismutase.
AB  - BACKGROUND AND PURPOSE: Extracellular superoxide dismutase (ECSOD) is highly
      expressed in the wall of blood vessels and plays an important role in modulation
      of vascular function in extracranial arteries. Expression of ECSOD appears to
      affect cerebral vascular responses during disease states. Effects of ECSOD on
      dilator function in cerebral arterioles, however, have not been fully elucidated.
      In the present study, we examined effects of ECSOD deficiency on cerebrovascular
      reactivity under control conditions and during oxidative stress. METHODS: Dilator
      responses of cerebral arterioles were examined in cranial windows in vivo in
      anesthetized ECSOD-deficient (-/-) and wild-type (+/+) mice under normal
      conditions and during oxidative stress induced by angiotensin II. RESULTS: Total
      SOD activity in the aorta in ECSOD-/- mice (176+/-24 [mean+/-SEM] U/mg) was
      approximately 30% lower than in ECSOD+/+ mice (270+/-38, P=0.051). Dilator
      responses to acetylcholine (10 micromol/L) in cerebral arterioles were similar
      under control conditions in ECSOD+/+ (34+/-5% changes in diameter) and -/- mice
      (32+/-4%). Angiotensin II (500 nmol/L for 30 minutes) tended to reduce responses
      to acetylcholine in ECSOD+/+ mice (not significant) and significantly impaired
      responses in ECSOD-/- mice (42% reduction, P<0.05). Tempol (1 mmol/L), a
      scavenger of superoxide, restored the impaired dilator responses in ECSOD-/-
      mice. Responses to nitroprusside in cerebral arterioles were similar in ECSOD+/+
      and -/- mice and were not affected by angiotensin II nor by tempol. CONCLUSIONS:
      ECSOD deficiency has little effect on cerebrovascular reactivity in control
      conditions but plays an important role in the regulation of vascular tone during
      oxidative stress produced by angiotensin II.

PMID- 17008609
TI  - Validity of a virtual environment for stroke rehabilitation.
AB  - BACKGROUND AND PURPOSE: Virtual environments for use in stroke rehabilitation are
      in development, but there has been little evaluation of their suitability for
      this purpose. We evaluated a virtual environment developed for the rehabilitation
      of the task of making a hot drink. METHODS: Fifty stroke patients undergoing
      rehabilitation in a UK hospital stroke unit were involved. The performance of
      stroke rehabilitation patients when making a hot drink had the neurological
      impairments associated with performance of this task, and the errors observed
      were compared for standardized task performance in the real world and in a
      virtual environment. Neurological impairments were measured using standardized
      assessments. Errors in task performance were assessed rating video recordings and
      classified into error types. RESULTS: Real-world and virtual environment
      performance scores were not strongly associated (rho=0.30; P<0.05). Performance
      scores in both settings were associated with age, Barthel ADL score, Mini Mental
      State Examination score, and tests of visuospatial function. Real-world
      performance only was associated with arm function and sequencing ability. Virtual
      environment performance only was associated with language function and praxis.
      Participants made different errors during task performance in the real world and
      in the virtual environment. CONCLUSIONS: Although this virtual environment was
      usable by stroke rehabilitation patients, it posed a different rehabilitation
      challenge from the task it was intended to simulate, and so it might not be as
      effective as intended as a rehabilitation tool. Other virtual environments for
      stroke rehabilitation in development require similar evaluation.

PMID- 17008610
TI  - Early intravenous infusion of sodium nitrite protects brain against in vivo
      ischemia-reperfusion injury.
AB  - BACKGROUND AND PURPOSE: The rate of nitric oxide (NO) generation from nitrite is
      linearly dependent on reductions in oxygen and pH levels. Recently, nitrite
      derived NO has been reported to exert a profound protection against liver and
      heart ischemia-reperfusion injury. In this study, we hypothesized that nitrite
      would be reduced to NO in the ischemic brain and exert NO-dependent
      neuroprotective effects. METHODS: Cerebral ischemia-reperfusion injury was
      induced by intraluminal thread occlusion of middle cerebral artery in the adult
      male rats. Solutions of sodium nitrite were infused intravenously at the time of
      reperfusion. Sodium nitrate and carboxy-PTIO (30 minutes before ischemic
      surgery), a direct NO scavenger, were infused for comparisons. RESULTS: Nitrite
      reduced infarction volume and enhanced local cerebral blood flow and functional
      recovery. The effects were observed at concentrations of 48 nmol and 480 nmol,
      but not at 4800 nmol nitrite and 480 nmol nitrate. The neuroprotective effects of
      nitrite were inhibited completely by the carboxy-PTIO. The 480 nmol nitrite
      attenuated dihydroethidium activity, 3-nitrotyrosine formation, and lipid
      peroxidation in the ischemic brain. CONCLUSIONS: Nitrite exerted profound
      neuroprotective effects with antioxidant properties in the ischemic brains. These
      results suggest that nitrite, as a biological storage reserve of NO, may be a
      novel therapeutic agent in the setting of acute stroke.

PMID- 17008611
TI  - Cortical neuronal apoptosis in CADASIL.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is caused by mutations of the NOTCH3
      gene and is a model of pure vascular dementia. Cortical atrophy has been reported
      to be associated with cognitive decline in the disease, although the underlying
      mechanism is unknown. We postulated that apoptosis may be involved in this
      process. METHODS: We report the clinical history, magnetic resonance imaging
      findings, and pathologic examinations of 4 patients (2 of whom were demented) who
      died from complications of the disease. Apoptosis was evaluated in brain tissue
      using antibodies against activated caspase3 and in situ end labeling assays for
      DNA fragmentation. RESULTS: Widespread neuronal apoptosis in the cerebral cortex
      (predominantly in layers 3 and 5) was observed in all patients. This was not seen
      in 3 non-CADASIL controls. Semiquantitative analysis suggested that apoptosis was
      more extensive in the presence of larger load of subcortical ischemic lesions and
      smaller brain volumes. CONCLUSIONS: Neuronal apoptosis may be involved in
      cortical atrophy in CADASIL and appears related to the burden of subcortical
      ischemic lesions. These findings may have important implications in other small
      vessel diseases and may provide a potential target for future therapeutic
      interventions.

PMID- 17008612
TI  - Neuroprotection by a central nervous system-type prostacyclin receptor ligand
      demonstrated in monkeys subjected to middle cerebral artery occlusion and
      reperfusion: a positron emission tomography study.
AB  - BACKGROUND AND PURPOSE: Recently, we found that a novel subtype of prostacyclin
      (PGI(2)) receptor clearly distinct from the peripheral subtype in terms of ligand
      specificity is expressed in the central nervous system (CNS). (15R)-16-m-tolyl
      17,18,19,20-tetranorisocarbacyclin (15R-TIC) was synthesized and demonstrated to
      be a specific ligand for this CNS-type PGI(2) receptor. Previously, we
      demonstrated 15R-TIC to be neuroprotective in vivo during transient forebrain
      ischemia in gerbils and permanent middle cerebral artery occlusion (MCAO) in
      rats. Furthermore, this compound was shown to exert an anti-apoptotic effect on
      primary cultured hippocampal neurons, indicating its neuroprotective effect
      against ischemic insults occurs via direct action on CNS-type PGI(2) receptor.
      METHODS: Local cerebral hemodynamics and oxygen metabolism were measured
      simultaneously by using positron emission tomography with the (15)O steady-state
      method, before and up to 18 hours after 3-hour transient MCAO reperfusion in
      cynomolgus monkeys. Methyl ester of 15R-TIC (50 microg/kg, n=4) or its vehicle
      (10% Intralipos, n=4) was injected intravenously within 5 minutes after onset of
      MCAO and continuously infused for 5 hours (50 microg/kg per hour). RESULTS:
      Neuropathology showed that 15R-TIC significantly reduced cortical damage after 3
      hour MCAO. Positron emission tomography results showed 15R-TIC significantly
      reduced the volume of "infarct" region of interest and attenuated the decrease in
      cerebral metabolic rate of oxygen and oxygen extraction fraction, and these
      protective effects were not attributable to improvement of cerebral circulation.
      CONCLUSIONS: These results suggest that 15R-TIC has a potent neuroprotective
      effect against focal cerebral ischemia in a monkey MCAO via its direct action on
      CNS-type PGI(2) receptors.

PMID- 17008613
TI  - Plasma S100B level after acute spontaneous intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: We sought to determine plasma S100B level after acute
      (<24 hours) spontaneous intracerebral hemorrhage (ICH) and to study its relation
      with neurological outcome. METHODS: We determined S100B concentration on plasma
      samples from 78 ICH patients on admission. Clinical (Glasgow Coma Scale and
      National Institutes of Health Stroke Scale [NIHSS] scores) and radiological
      information (ICH and perihematomal edema volumes) were collected at baseline and
      follow-up visits. Early neurological deterioration, defined as the increase of
      >or=4 points in the NIHSS score at 48 hours, and unfavorable outcome (modified
      Rankin Scale >2) at 3 months were also recorded. RESULTS: The median S100B level
      was higher than our laboratory reference values for healthy controls (103.6
      versus 48.5 pg/mL; P<0.001) and a positive correlation was observed between S100B
      level and baseline ICH volume (r=0.45; P<0.0001). The median S100B level was
      higher in patients who deteriorated early (256.8 versus 89.7 pg/mL; P=0.001) and
      also in patients with an unfavorable outcome (136 versus 75.9 pg/mL; P=0.003).
      Multivariate analysis showed baseline ICH volume as the best predictor for both
      early neurological deterioration (odds ratio 15; 95% CI, 2.9 to 76.3) and
      unfavorable outcome at 3 months (odds ratio 17; 95% CI, 2.0 to 142). CONCLUSIONS:
      Increased S100B level is found after acute spontaneous ICH, in association with a
      worse early and late evolution, and closely related to initial hematoma volume.

PMID- 17008614
TI  - Heritability of MRI lesion volume in CADASIL: evidence for genetic modifiers.
AB  - BACKGROUND AND PURPOSE: The phenotypic expressivity shows striking variability
      among individuals with CADASIL (cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy), a small vessel disease caused by
      mutations in NOTCH3. However, little is known about the factors that underlie
      this variability. We sought to quantify the contribution of modifying genetic
      effects to individual differences in the volume of cerebral ischemic lesions.
      METHODS: One hundred and fifty-one affected individuals (mean age+/-SD=45.7+/
      10.4) from 95 unrelated families with CADASIL underwent MRI. The volume of
      lesions visible on T2-weighted images and the intracranial volume (ICV) were
      quantified and vascular risk factors were assessed. Because of a skewed
      distribution, lesion volume measures were square-root transformed. Variance
      component methods were used to estimate the heritability of lesion volumes (ie,
      the proportion of variation caused by additive genetic factors) after adjusting
      for covariates. RESULTS: In multivariate analyses, higher age, a larger ICV, and
      a higher diastolic blood pressure were independently associated with a larger
      volume of T2-visible lesions (all P<0.05). After adjustment for age the point
      estimate for the heritability of the square-root-transformed measure of T2 lesion
      volume was 0.634 (SE=+/-0.286). Adjustment for age, sex, ICV, and diastolic blood
      pressure increased the estimated heritability to 0.738 (SE+/-0.255). CONCLUSIONS:
      Heritability estimates in CADASIL suggest a strong modifying influence of genetic
      factors distinct from the causative NOTCH3 mutation on the amount of ischemic
      brain lesions. These findings justify a systematic search for genetic variants
      that modify disease progression.

PMID- 17008615
TI  - Economic evaluation of Australian stroke services: a prospective, multicenter
      study comparing dedicated stroke units with other care modalities.
AB  - BACKGROUND AND PURPOSE: Level I evidence from randomized controlled trials
      demonstrates that the model of hospital care influences stroke outcomes; however,
      the economic evaluation of such is limited. An economic appraisal of 3 acute
      stroke care models was facilitated through the Stroke Care Outcomes: Providing
      Effective Services (SCOPES) study in Melbourne, Australia. The aim was to
      describe resource use up to 28 weeks poststroke for each model and examine the
      cost-effectiveness of stroke care units (SCUs). METHODS: A prospective,
      multicenter, cohort study design was used. Costs and outcomes of stroke patients
      receiving 100% treatment in 1 of 3 inpatient care models (SCUs, mobile service,
      conventional care) were compared. Health-sector resource use up to 28 weeks was
      measured in 1999. Outcomes were thorough adherence to a suite of important
      clinical processes and the number of severe inpatient complications. RESULTS: The
      sample comprised 395 participants (mean age 73 [SD 14], 77% first-ever strokes,
      males 53%). When compared with conventional care (n=84), costs for mobile service
      (n=209) were significantly higher (P=0.024), but borderline for SCU (n=102,
      P=0.08; 12,251 Australian dollars; 15,903 Australian dollars; 15,383 Australian
      dollars respectively). This was primarily explained by the greater use of
      specialist medical services. The incremental cost-effectiveness of SCUs over
      conventional care was 9867 Australian dollars per patient achieving thorough
      adherence to clinical processes and 16,372 Australian dollars per patient with
      severe complications avoided, based on costs to 28 weeks. CONCLUSIONS: Although
      acute SCU costs are generally higher, they are more cost-effective than either
      mobile service or conventional care.

PMID- 17008616
TI  - Hyperoxic exposure leads to nitrative stress and ensuing microvascular
      degeneration and diminished brain mass and function in the immature subject.
AB  - BACKGROUND AND PURPOSE: Neonates that survive very preterm birth have a high
      prevalence of cognitive impairment in later life. A common factor detected in
      premature infants is their postnatal exposure to high oxygen tension relative to
      that in utero. Hyperoxia is known to elicit injury to premature lung and retina.
      Because data on the exposure of the brain to hyperoxia are limited, we studied
      the effects of high oxygen on this tissue. METHODS: Rat pups were exposed from
      birth until day 6 to 21% or 80% O(2). Cerebral vascular density was quantified by
      lectin immunohistochemistry. Immunoblots for several proteins were performed on
      brain extracts. We assessed cerebral functional deficits by visual evoked
      potentials. RESULTS: Exposure of pups to hyperoxia leads to cerebral
      microvascular degeneration, diminished brain mass, and cerebral functional
      deficits. These effects are preceded by an upregulation of endothelial nitric
      oxide synthase (eNOS) in cerebral capillaries and a downregulation of Cu/Zn
      superoxide dismutase (SOD). The imbalance in nitric oxide (NO) production and
      antioxidant defenses favors the formation of nitrating agents in the microvessels
      revealed by increased nitrotyrosine (3-nt) immunoreactivity and decreased
      expression of NF-kappaB and the dependent vascular endothelial growth factor
      receptor 2. NOS inhibitors and eNOS deletion as well as an SOD mimetic (CuDIPS)
      restore vascular endothelial growth factor receptor-2 levels and nearly abolish
      the vasoobliteration. NOS inhibitors and SOD mimetic also prevent O(2)-induced
      diminished brain mass and functional deficit. CONCLUSIONS: Data identify NO and
      nitrating agents as major mediators of cerebral microvascular damage, ensuing
      impaired brain development and function in immature subjects exposed to
      hyperoxia.

PMID- 17008617
TI  - Off-pump surgery is associated with reduced occurrence of stroke and other
      morbidity as compared with traditional coronary artery bypass grafting: a meta
      analysis of systematically reviewed trials.
AB  - BACKGROUND AND PURPOSE: There is growing enthusiasm for coronary artery bypass
      grafting (CABG) without cardiopulmonary bypass (CPB). Although deleterious
      effects of CPB are known, it remains to be proven that avoiding CPB will result
      in reduction in morbidity. We sought to determine whether off-pump surgery is
      associated with reduced occurrence of adverse outcomes as compared with CABG with
      CPB. METHODS: Studies were identified by searching the MEDLINE, EMBASE and the
      Cochrane Register 1980 to 2006 (February). We also searched the reference lists
      of randomized clinical trials (RCT) and reviews to look for additional studies.
      STUDY SELECTION: RCTs comparing off-pump surgery to CABG with CPB. No restriction
      applied on the size of the trial or end point reports. DATA EXTRACTION: 2
      reviewers independently searched for studies, read abstracts and abstracted all
      data. DATA SYNTHESIS: combined estimates were obtained using fixed or random
      effect meta-analyses. Relative risks and risk differences were calculated.
      Heterogeneity was assessed using chi(2) and I(2) values. RESULTS: There were 3996
      patients enrolled in 41 RCTs (mean age 62, 22% female). No study reported
      information on race. Off-pump CABG was associated with a 50% reduction in the
      relative risk of stroke (95% CI, 7% to 73%), 30% reduction in atrial fibrillation
      (AF; 95% CI, 16% to 43%) and 48% reduction in wound infection (95% CI, 26% to
      63%) with no heterogeneity among RCTs. This translated into avoidance of 10
      strokes, 80 cases of AF and 40 infections per 1000 CABG. Fewer distal grafts were
      performed and there was evidence for >10 reinterventions per 1000 with off-pump
      CABG. Long-term follow-up is not yet reported in the trials. CONCLUSIONS: Off
      pump CABG is associated with reduced risk of stroke, AF and infections as
      compared with CABG with CPB. Evidence should be generalized taking into account
      RCT enrollment limitations, drawbacks related to training requirements,
      propensity to perform fewer grafts and likely reinterventions after off-pump
      surgery.

PMID- 17008618
TI  - Direct demonstration that repetitive transcranial magnetic stimulation can
      enhance corticospinal excitability in stroke.
AB  - BACKGROUND AND PURPOSE: Preliminary studies suggest that electrical stimulation
      of the damaged cortex may be able to enhance motor recovery after stroke. The
      hypothesis has been that this increases cortical excitability, making it easier
      for the system to respond to and learn from conventional physiotherapy. However,
      there is no direct evidence that the cortex of patients with stroke can respond
      in this fashion; hence, the basis of these new approaches has been questioned.
      METHODS: We had the opportunity to evaluate directly the effects of noninvasive
      cortical stimulation on the excitability of corticospinal output from the damaged
      hemisphere of a chronic stroke patient who had epidural electrodes implanted in
      the upper dorsal cord for treatment of pain. RESULTS: We found that it was
      possible to enhance corticospinal activity evoked by single test stimuli.
      CONCLUSIONS: This study confirms directly that it is possible to noninvasively
      manipulate cortical excitability in stroke.

PMID- 17008620
TI  - Candidate gene polymorphisms do not differ between newborns with stroke and
      normal controls.
AB  - BACKGROUND AND PURPOSE: Neonatal stroke is increasingly recognized with an
      estimated incidence of one in 4000 live births per year. Pathways involved in the
      pathophysiology of neonatal stroke are diverse and may include thrombosis and
      thrombolysis, vascular reactivity, and inflammation. METHODS: We compared
      frequencies of polymorphisms in genes regulating thrombosis and thrombolysis,
      nitric oxide, cytokines, vascular tone, and cell adhesion in a hospital-based
      cohort of 59 newborns with stroke relative to a random sample of 437 California
      newborns. RESULTS: Of the 31 polymorphisms evaluated, no variant allele was
      significantly more common than the reference allele in newborns with stroke than
      in the general population. CONCLUSIONS: Using a series of polymorphisms in
      pathways implicated in the etiology of stroke, newborns with stroke were not
      distinguished from a normal control group. Further studies are needed to
      determine the interaction of genetic polymorphisms with environmental risk
      factors in the pathogenesis of neonatal stroke.

PMID- 17008621
TI  - Conjugate eye deviation in acute stroke: incidence, hemispheric asymmetry, and
      lesion pattern.
AB  - BACKGROUND AND PURPOSE: The authors studied clinical features and lesion patterns
      associated with conjugate eye deviation (CED) in acute stroke. METHODS:
      Consecutive patients with supratentorial stroke (<6 hours after symptom onset)
      were prospectively recruited. CED was classified according to the National
      Institute of Health Stroke Scale (NIHSS) item "gaze palsy" as being forced,
      partial, or absent. Lesion patterns on diffusion-weighted images (DWI) were
      analyzed in 46 patients using a normalization procedure for direct comparisons
      between patients. Perfusion data were analyzed for a subset of patients. RESULTS:
      Partial CED was found in 7 (6%) and forced CED in 31 (26.7%) of 116 patients.
      Forced and partial CED were associated with higher initial NIHSS scores compared
      with patients without CED (16 and 10 versus 5; P<0.05). DWI lesion volume was
      larger in patients with CED (103.24+/-102.4 mL, mean+/-SD) as compared with
      patients without CED (17+/-34.98 mL, P<0.001). CED was more frequent in right
      hemispheric stroke (44.6% versus 23%, P<0.02). DWI pattern analysis in patients
      with CED with right hemispheric stroke revealed a network of affected regions,
      including basal ganglia and temporoparietal cortex. In left hemispheric CED,
      lesions were larger than in patients without CED, but no consistent pattern could
      be established. In a subset of selected patients with CED, a small
      temporoparietal perfusion deficit was sufficient to elicit CED. CONCLUSIONS:
      Selective dysfunction of cortical areas involved in spatial attention and control
      of eye movements is sufficient to cause CED in patients with acute stroke.
      However, in the majority of cases, CED is an indicator of large infarcts
      involving more than one area, including both cortical and subcortical structures.

PMID- 17008622
TI  - Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white
      matter lesions after chronic cerebral hypoperfusion in rodents.
AB  - BACKGROUND AND PURPOSE: Cerebrovascular white matter (WM) lesions contribute to
      cognitive impairment and motor dysfunction in the elderly. A disruption of the
      blood-brain barrier (BBB) is believed to be a critical early event leading to
      these WM lesions. Previous studies have suggested the involvement of matrix
      metalloproteinase-2 (MMP-2) in BBB disruptions and the upregulation of MMP-2
      after chronic cerebral hypoperfusion in a rat model. In the present study, we
      asked whether MMP-2 is involved in the BBB disruption and the subsequent WM
      lesions after chronic cerebral hypoperfusion. METHODS: We compared the severity
      of white matter lesions in rats after chronic cerebral hypoperfusion with or
      without an MMP inhibitor. Then, we also induced the chronic cerebral
      hypoperfusion in wild-type and MMP-2-null mice. RESULTS: In the rats treated with
      a relatively selective MMP-2 inhibitor, AG3340, the WM lesions after chronic
      cerebral hypoperfusion were significantly less severe, and the number of
      activated astroglia and microglia were also significantly lower as compared with
      the vehicle-treated rats. Gene knockout of MMP-2 also reduced the severity of the
      WM lesions and the number of activated astroglia and microglia in a mice system.
      In both rodents, the disruption of BBB function, as assessed by IgM staining and
      the Evans blue extravasation test, was less severe when MMP-2 activity was
      attenuated. CONCLUSIONS: These findings indicate that MMP-2 plays a critical role
      in the BBB disruption, glial cell activation, and WM lesions after chronic
      cerebral hypoperfusion and suggest the potential value of MMP-2 inhibitors as a
      therapeutic tool in cerebrovascular WM lesions.

PMID- 17008623
TI  - Tissue oxygen index: thresholds for cerebral ischemia using near-infrared
      spectroscopy.
AB  - BACKGROUND AND PURPOSE: To date, the clinical application of near infrared
      spectroscopy in the adult brain has been limited. The NIRO 300 (Hamamatsu
      Photonics) provides a continuous measurement of tissue oxygen index (TOI) using
      spatially resolved spectroscopy. Although TOI reflects cerebral oxygenation to a
      high degree of sensitivity and specificity, to become a useful clinical tool,
      thresholds for cerebral ischemia need to be defined. This study has attempted to
      identify a quantifiable TOI threshold for ischemia in the adult brain. METHODS:
      One hundred sixty-seven patients undergoing carotid endarterectomy were studied.
      The NIRO 300 was incorporated into an established multimodal monitoring system
      enabling observations of cerebral hemodynamic changes under highly controlled
      conditions. Changes in TOI (%DeltaTOI) on clamping the internal carotid artery
      were compared with intracranial blood flow (middle cerebral artery flow velocity)
      and cerebral function monitoring to identify and quantify periods of cerebral
      ischemia. RESULTS: Significant correlation was seen between changes in middle
      cerebral artery flow velocity and DeltaTOI on clamping (r=0.74, P=0.0001). Thirty
      one patients showed cerebral ischemia on internal carotid artery clamping as
      defined by a sustained fall in cerebral function monitoring. A threshold for
      %DeltaTOI of -13 was identified, above which no patients showed any evidence of
      ischemia on clamping. This threshold provided 100% sensitivity and 93.2%
      specificity for patients satisfying the preset criteria for cerebral ischemia.
      CONCLUSIONS: These data demonstrate the potential to identify TOI-quantified
      thresholds for cerebral ischemia in the adult brain and thus improve the clinical
      use of near infrared spectroscopy. Our observations have defined a drop in TOI
      (13%) that can be adopted as a threshold for severe cerebral ischemia with high
      sensitivity and specificity.

PMID- 17008624
TI  - Prevalence of depression and use of antidepressant medication at 5-years
      poststroke in the North East Melbourne Stroke Incidence Study.
AB  - BACKGROUND AND PURPOSE: There are few data on the prevalence or treatment of
      depression from unselected populations long-term poststroke. We assessed the
      prevalence of depression and antidepressant use at 5-years poststroke in an
      unselected stroke population. METHODS: Five-year survivors from a prospective
      community-based stroke incidence study were assessed for depression with the
      Irritability, Depression and Anxiety Scale. Medications indicated primarily for
      treatment of depression were recorded. RESULTS: At 5-years poststroke, 441 (45%)
      of 978 incident cases were alive (mean age=74+/-15 years, 49% female). Seventeen
      percent of those assessed were depressed. Twenty-two percent with depression were
      taking an antidepressant medication. Of those taking an antidepressant, 72% were
      not depressed. CONCLUSIONS: Although nearly one-fifth of survivors were
      depressed, few were taking antidepressants. Further exploration of this low level
      of treatment is warranted.

PMID- 17008625
TI  - The impact of poststroke depression on healthcare use by veterans with acute
      stroke.
AB  - BACKGROUND AND PURPOSE: Poststroke depression (PSD) is common among stroke
      survivors, and it is associated with worse functional outcomes and increased
      poststroke mortality. Limited information is available about its impact on
      healthcare use. This study assessed the impact of PSD on healthcare use by
      veterans with acute stroke. METHODS: In this retrospective, observational
      national study, 5825 veterans with acute stroke were identified from Veterans
      Affairs' (VA) inpatient databases. To determine the patients' comprehensive PSD
      and use status, VA and Medicare fee-for-service inpatient and outpatient as well
      as VA pharmacy data were used. PSD was established if a patient had an inpatient
      or outpatient depression diagnosis or if a patient received one of the
      antidepressants within the VA 12 months postindex stroke. Healthcare use referred
      to the number of hospital stays, outpatient visits, and cumulative length of
      inpatient stays under both VA and Medicare fee-for-service programs. Poisson
      regression was fitted to estimate the impact of PSD on use controlling for
      sociodemographic, clinical, and disease severity factors. RESULTS: Forty-one
      percent of the sample had PSD. After adjusting for patient demographic and
      clinical factors, we found that the patients with stroke with PSD had
      significantly (P<0.0001) more hospitalizations, outpatient visits, and longer
      length of stays 12 months poststroke compared with these patients with stroke
      without PSD. CONCLUSIONS: Patients with PSD had greater 12-month poststroke
      healthcare use even when controlling for other demographic and clinical
      variables. Early detection and appropriate management of PSD for veterans with
      acute stroke may help reduce their poststroke healthcare use.

PMID- 17008626
TI  - Transcranial Doppler monitoring of transcervical carotid stenting with flow
      reversal protection: a novel carotid revascularization technique.
AB  - BACKGROUND AND PURPOSE: Transfemoral carotid stenting, despite becoming very
      frequent, has some limitations such as difficult groin access in few patients,
      lack of distal protection during filter placement, or embolization despite
      protection. Transcervical stenting (TCS) is a novel technique during which a
      common carotid to jugular vein shunt is placed creating a protective reversal
      flow in the internal carotid artery after proximal common carotid artery (CCA)
      clamping. We aim to study, with transcranial Doppler (TCD), cerebral flow changes
      and microemboli detection during transcervical stenting. METHODS: From September
      2005 to March 2006, of 65 consecutive patients eligible for carotid
      revascularization, 23 were considered high risk (sapphire criteria) and underwent
      TCS. Neurologic examination was performed before and after the procedure by a
      neurologist and a preprocedure vascular reactivity TCD examination was done in
      all patients. RESULTS: After CCA clamping, flow inversion was observed in the
      anterior cerebral artery, supplying blood to the middle cerebral artery (MCA) and
      internal carotid artery (reversal). TCD did not detect any air/solid emboli
      during stent deployment and angioplasty confirming the reversal flow protection
      hypothesis. Mean reversal flow time was 15.4 minutes; in all cases, substantial
      MCA flow was present during CCA clamping (initial mean velocity 30 cm/s), and a
      slow gradual increase was observed traducing collateral flow recruitment (mean
      velocity after 5 minutes 36 cm/s, P<0.001). Flow increase was observed in all
      patients except in those with preprocedural exhausted ipsilateral vascular
      reactivity (16% versus 2%, P=0.036). The only in-procedure complication was one
      transient ischemic attack. After CCA unclamping, normal antegrade flow was
      restored in anterior cerebral artery and mean final MCA velocity increased 16%
      according to preprocedure flow. CONCLUSIONS: TCS with protective internal carotid
      artery flow reversal can eliminate showers of micoremboli during stent deployment
      making it a promising carotid revascularization technique in high-risk patients
      with carotid stenosis.

PMID- 17008627
TI  - Carotid plaque surface irregularity predicts ischemic stroke: the northern
      Manhattan study.
AB  - BACKGROUND AND PURPOSE: There is scant population-based evidence regarding
      extracranial carotid plaque surface irregularity and ischemic stroke. Using a
      prospective cohort design, we evaluated the association of carotid plaque surface
      irregularity and the risk of ischemic stroke in a multiethnic population.
      METHODS: High-resolution B-mode ultrasound of the carotid arteries was performed
      in 1939 stroke-free subjects (mean age 69+/-10.0 years; 59% women; 53% Hispanic,
      25% black, 22% white). Plaque was defined as a focal protrusion 50% greater than
      the surrounding area and localized along the extracranial carotid tree (internal
      carotid artery/bifurcation vs common carotid artery). Plaque surface was
      categorized as regular or irregular. Cox proportional hazard models were used to
      assess the association of surface characteristics and the risk of ischemic
      stroke. RESULTS: Among 1939 total subjects, carotid plaque was visualized in
      56.3% (1 plaque: 21.6%, >1 plaque: 34.7%, irregular plaque: 5.5%). During a mean
      follow up of 6.2 years after ultrasound examination, 69 ischemic strokes
      occurred. Unadjusted cumulative 5-year risks of ischemic stroke were: 1.3%, 3.0%,
      and 8.5% for no plaque, regular plaque, and irregular plaque, respectively. After
      adjusting for demographics, traditional vascular risk factors, degree of
      stenosis, and plaque thickness, presence of irregular plaque (vs no plaque) was
      independently associated with ischemic stroke (Hazard ratio, 3.1; 95% CI, 1.1 to
      8.5). CONCLUSIONS: The presence of irregular carotid plaque independently
      predicted ischemic stroke in a multiethnic cohort. Plaque surface irregularities
      assessed by B-mode ultrasonography may help identify intermediate- to high-risk
      individuals beyond their vascular risk assessed by the presence of traditional
      risk factors.

PMID- 17008628
TI  - Enriched environment attenuates cell genesis in subventricular zone after focal
      ischemia in mice and decreases migration of newborn cells to the striatum.
AB  - BACKGROUND AND PURPOSE: Cells proliferate continuously in the adult mammalian
      brain, and in rodents, cell genesis is affected by housing conditions and brain
      injury. Increase in neurogenesis after brain ischemia has been postulated to be
      linked to functional recovery after stroke. Housing rodents in an enriched
      environment improves motor function after stroke injury. We have investigated
      whether changes in cell genesis can explain the beneficial effects of an enriched
      environment. METHODS: Intact mice and mice subjected to transient occlusion of
      the middle cerebral artery were exposed to an enriched environment for 1 month.
      Bromodeoxyuridine was injected daily to label proliferating cells during the
      first postischemic week. Newborn cells were analyzed immunohistochemically after
      4 weeks. RESULTS: The enriched environment increased neurogenesis in the dentate
      gyrus in both intact and stroke-injured animals. An increased number of newborn
      cells was found in the subventricular zone of stroke-injured mice, but not in
      injured mice exposed to an enriched environment. Also, the number of newborn
      astrocytes (BrdU+/S-100beta+ cells), neuroblasts (dcx+ cells), and reactive
      astrocytes (vimentin mRNA) in the striatum ipsilateral to the ischemic injury was
      markedly attenuated and new adult neurons (BrdU+/NeuN+) were not found. The
      enriched environment did not affect infarct size or mortality. CONCLUSIONS: An
      enriched environment after experimental stroke increased neurogenesis in the
      hippocampus, whereas there was a decreased cell genesis and migration of
      neuroblasts and newborn astrocytes in the striatum.

PMID- 17008629
TI  - Progressive decline in stroke mortality in Brazil from 1980 to 1982, 1990 to
      1992, and 2000 to 2002.
AB  - BACKGROUND AND PURPOSE: We describe the trends in stroke mortality in Brazil
      during 3 decades and investigate their differences according to regional
      disparities, sex, and age distributions. METHODS: Official data on mortality and
      population estimates were retrieved to calculate standardized mortality rates
      (with the 1980 Brazilian population as a reference) in 6 age strata and in the 5
      political regions for the initial period (3 first years) of the 1980, 1990, and
      2000 decades. Data were corrected for undefined causes of death. The Poisson
      model was used to estimate risk reduction during the 3 decades and to study the
      interaction between those rates and sex, age strata, and regions. RESULTS: The
      stroke standardized mortality rate decreased consistently in the last 20 years,
      from 68.2 to 40.9 per 100,000 habitants. This reduction paralleled a decrease in
      total cardiovascular mortality rates in the same period, from 208.2 to 126.1 per
      100,000 habitants. The reduction in stroke standardized mortality rate was
      detected in men and women and in all age strata. The reduction was evident in all
      geopolitical regions of the country, with the wealthiest regions' exhibiting
      higher initial rates and more marked standardized mortality rate reductions. The
      risk of dying of stroke in the period 2000 to 2002 was 0.45 (95% CI, 0.44 to
      0.45) of that found in the period 1980 to 1982. CONCLUSIONS: The risk of dying of
      stroke in Brazil declined dramatically between the initial period in the early
      1980s and the early 2000s. The decline was especially marked in the most
      developed regions and may reflect an improvement in general health conditions
      during the study period.

PMID- 17008630
TI  - Impact of basilar artery vasospasm on outcome in patients with severe cerebral
      vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to evaluate the
      impact of basilar artery (BA) vasospasm on outcome in patients with severe
      vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Sixty-five
      patients with clinically suspect severe cerebral vasospasm after aSAH underwent
      cerebral angiography before endovascular treatment. Vasospasm severity was
      assessed for each patient by transcranial Doppler measurements, angiography, and
      (99m)Tc-ethylcysteinate dimer single-photon emission computed tomography (ECD
      SPECT) imaging. Percentage of BA narrowing was calculated in reference to the
      baseline angiogram. RESULTS: BA narrowing >or=25% was found in 23 of 65 patients,
      and delayed brain stem (BS) hypoperfusion, as estimated by ECD-SPECT, was found
      in 16. Fourteen of 23 patients with BA narrowing >or=25% experienced BS
      hypoperfusion, whereas only 2 of 42 patients with >or=25% BA narrowing
      experienced BS ischemia (P<0.001). Stepwise logistic regression after adjusting
      for age with Hunt and Hess grade, Fisher grade, hydrocephalus, and aneurysmal
      location as covariables revealed BA narrowing >or=25% and delayed BS
      hypoperfusion to be significantly and independently associated with unfavorable 3
      month outcome (P=0.0001; odds ratio, 10.1; 95% CI, 2.5 to 40.8; and P=0.007; odds
      ratio, 13.8, 95% CI, 2.18 to 91.9, respectively). CONCLUSIONS: These findings
      suggest for the first time that BA vasospasm after aSAH is an independent and
      significant prognostic factor associated with poor outcome in patients with
      severe cerebral vasospasm requiring endovascular therapy. Further study should be
      done to evaluate the role of interventional therapy on outcome in patients with
      posterior circulation vasospasm.

PMID- 17008631
TI  - Homocysteine and carotid intima-media thickness in a german population: lack of
      clinical relevance.
AB  - BACKGROUND AND PURPOSE: Common carotid artery intima-media thickness (CCA IMT) is
      a predictor of stroke. This study aimed to analyze whether homocysteine (Hcys)
      metabolism influences CCA IMT. METHODS: We analyzed the association of personal,
      clinical, and biochemical data (multivariate analysis) and of 9 polymorphisms
      involved in Hcys metabolism (ANOVA) with CCA IMT in 714 individuals of 187
      families. RESULTS: CCA IMT was significantly predicted by age, sex, creatinine
      levels, lipoprotein(a) levels, pack-years of smoking, the presence of
      hypertension, and the presence of diabetes mellitus but not by Hcys levels.
      Homozygosity for the T allele of the polymorphism methylenetetrahydrofolate
      reductase c.677C>T was significantly associated with higher Hcys levels but not
      with a higher CCA IMT. CONCLUSIONS: These data do not support the thesis that
      elevated Hcys levels are causally involved in cerebrovascular disease.

PMID- 17008632
TI  - Combined measurement of carotid stiffness and intima-media thickness improves
      prediction of complex aortic plaques in patients with ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We hypothesized that for the prediction or exclusion of
      aortic thrombi or plaques >or=4 mm, the combination of intima-media thickness
      (IMT) and distensibility (DC) of the common carotid arteries would be superior to
      the measurement of IMT alone. METHODS: We prospectively included 208 stroke
      patients (mean age, 60 years) undergoing transesophageal echocardiography for
      screening of aortic plaques. IMT and DC were determined by ultrasound, and DC was
      quantified by measuring blood pressure and the common carotid arteries diameter
      change on M-mode ultrasound during the cardiac cycle. RESULTS: Negative
      predictive values of IMT <0.9 mm and DC >or=24x10(-3)/kPa for the exclusion of
      aortic atheroma >or=4 mm were similar (92.0% and 91.7%, respectively). However,
      negative predictive values increased to 98.2% and to 100.0% for the exclusion of
      aortic thrombi when both parameters were combined. Positive predictive values of
      IMT >or=0.9 mm and DC <24 were lower (46.3%, 41.1%; respectively), but they also
      increased in combination (54.3%). CONCLUSIONS: Our findings suggest that IMT and
      DC represent different vessel wall properties and that measuring both parameters
      provides optimized characterization of carotid atherosclerosis. Combining IMT and
      DC increases the predictive power of carotid ultrasound, making transesophageal
      echocardiography dispensable for assessment of the aorta for those with normal
      carotid arteries and indispensable for those patients with carotid
      atherosclerosis.

PMID- 17008633
TI  - Sentinel headache and the risk of rebleeding after aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: The clinical significance of sentinel headaches in
      patients with subarachnoid hemorrhage (SAH) is still unknown. We investigated
      whether patients with a sentinel headache (SH) have a higher rate of rebleeding
      after SAH. METHODS: An SH was defined as a sudden, severe, unknown headache
      lasting >1 hour with or without accompanying symptoms, not leading to a diagnosis
      of SAH in the 4 weeks before the index SAH. Age, sex, smoking status, clinical
      grade, computed tomography (CT) findings, angiographic findings, placement of an
      external ventricular drain, and time to aneurysm obliteration were prospectively
      recorded. All rebleeding events were confirmed by CT. Outcome was assessed at 6
      months according to the modified Rankin Scale. RESULTS: Of 237 consecutive
      patients with SAH, 41 (17.3%) had an SH. Rebleeding occurred in 23 (9.7%) of all
      patients. Patients with an SH had a 10-fold increased odds of rebleeding compared
      with patients without SH. Aneurysm size and the total number of aneurysms were
      also significantly associated with rebleeding. There were no differences in age,
      sex, smoking, CT or angiographic findings, external ventricular drain placement,
      or time to aneurysm obliteration between groups. Patients with rebeeding had a
      significantly worse outcome. Logistic regression revealed the presence of an SH
      as an independent risk factor for rebleeding. CONCLUSIONS: In our study, patients
      with SAH who had an SH constituted a special group of patients with a 10-fold
      odds for early rebleeding. The presence of an SH may select candidates for
      ultraearly aneurysm obliteration or drug treatment.

PMID- 17008634
TI  - Medium-term variability of blood pressure and potential underdiagnosis of
      hypertension in patients with previous transient ischemic attack or minor stroke.
AB  - BACKGROUND AND PURPOSE: Blood pressure (BP) is a major risk factor for stroke.
      However, the variability of systolic and diastolic BP (SBP and DBP) means that
      single measurements do not provide a reliable measure of usual BP. Although 24
      hour ambulatory BP monitoring can correct for the effects of short-term
      variation, there is also important medium-term variability. The extent of medium
      term variability in BP is most marked in patients with a previous transient
      ischemic attack (TIA) or stroke. We studied the potential impact of this
      variability on the likely recognition of hypertension. METHODS: We analyzed
      multiple repeated measurements of BP in 3 large cohorts with a TIA or minor
      stroke: the UK-TIA trial (n=2098), the Dutch TIA trial (n=2953), and the European
      Carotid Surgery Trial (ECST; n=2646). Regression dilution ratios and coefficients
      of variation were calculated for SBP and DBP from baseline and repeated
      measurements during the subsequent 12 months. Categorization based on single
      baseline measurements was also compared with categorization based on the
      subsequent "usual" BP. RESULTS: The correlation between measurements of BP at
      baseline and 3 to 5 months later was poor (R(2) from 0.17 to 0.31 for SBP and
      from 0.10 to 0.20 for DBP). Categorization of patients by baseline values
      resulted in substantial misclassification in relation to usual BP. For example,
      of patients with an SBP <140 mm Hg at baseline, the percentage with a usual SBP
      >or=140 mm Hg was 31.6% in the UK-TIA trial, 48.2% in the Dutch TIA trial, and
      57.7% in the ECST. At least 3 consecutive measurements of SBP <120 mm Hg were
      required to be >90% certain that subsequent usual SBP would not be >or=140 mm Hg.
      CONCLUSIONS: Given the greater medium-term variability of BP in patients with a
      previous TIA or stroke than in the general population, single measurements of
      "normal" or "low" BP will substantially underestimate the true prevalence of
      hypertension.

PMID- 17008636
TI  - Trefoil factor family 3 peptide promotes human airway epithelial ciliated cell
      differentiation.
AB  - Human airway surface epithelium is frequently damaged by inhaled factors
      (viruses, bacteria, xenobiotic substances) as well as by inflammatory mediators
      that contribute to the shedding of surface epithelial cells. To regain its
      protective function, the epithelium must rapidly repair and redifferentiate. The
      Trefoil Factor Family (TFF) peptides are secretory products of many mucous cells.
      TFF3, the major TFF in the airways, is able to enhance airway epithelial cell
      migration, but the role of this protein in differentiation has not been defined.
      To identify the specific role of TFF3 in the differentiation of the human airway
      surface epithelium, we analyzed the temporal expression pattern of TFF3, MUC5AC,
      and MUC5B mucins (goblet cells) and ciliated cell markers beta-tubulin (cilia)
      and FOXJ1 (ciliogenesis) during human airway epithelial regeneration using in
      vivo humanized airway xenograft and in vitro air-liquid interface (ALI) culture
      models. We observed that TFF3, MUC5AC, MUC5B, and ciliated cell markers were
      expressed in well-differentiated airway epithelium. The addition of exogenous
      recombinant human TFF3 to epithelial cell cultures before the initiation of
      differentiation resulted in no change in MUC5AC or cytokeratin 13 (CK13, basal
      cell marker)-positive cells, but induced an increase in the number of FOXJ1
      positive cells and in the number of beta-tubulin-positive ciliated cells (P <
      0.05). Furthermore, this effect on ciliated cell differentiation could be
      reversed by specific epidermal growth factor (EGF) receptor (EGF-R) inhibition.
      These results indicate that TFF3 is able to induce ciliogenesis and to promote
      airway epithelial ciliated cell differentiation, in part through an EGF-R
      dependent pathway.

PMID- 17008635
TI  - Bioelectric properties of chloride channels in human, pig, ferret, and mouse
      airway epithelia.
AB  - The development of effective therapies for cystic fibrosis (CF) requires animal
      models that can appropriately reproduce the human disease phenotype. CF mouse
      models have demonstrated cAMP-inducible, non-CF transmembrane conductance
      regulator (non-CFTR) chloride transport in conducting airway epithelia, and this
      property is thought to be responsible for the lack of a spontaneous CF-like
      phenotype in the lung. Thus, an understanding of species diversity in airway
      epithelial electrolyte transport and CFTR function is critical to developing
      better models for CF. Two species currently being used in attempts to develop
      better animal models of CF include the pig and ferret. In the study reported
      here, we sought to comparatively characterize the bioelectric properties of in
      vitro polarized airway epithelia--from human, mouse, pig and ferret--grown at the
      air-liquid interface (ALI). Bioelectric properties analyzed include amiloride
      sensitive Na(+) transport, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid
      (DIDS)-sensitive Cl(-) transport, and cAMP-sensitive Cl(-) transport. In
      addition, as an index for CFTR functional conservation, we evaluated the ability
      of four CFTR inhibitors, including glibenclamide, 5-nitro-2-(3-phenylpropyl
      amino)-benzoic acid, CFTR (inh)-172, and CFTR(inh)-GlyH101, to block cAMP
      mediated Cl(-) transport. Compared with human epithelia, pig epithelia
      demonstrated enhanced amiloride-sensitive Na(+) transport. In contrast, ferret
      epithelia exhibited significantly reduced DIDS-sensitive Cl(-) transport.
      Interestingly, although the four CFTR inhibitors effectively blocked cAMP
      mediated Cl(-) secretion in human airway epithelia, each species tested
      demonstrated unique differences in its responsiveness to these inhibitors. These
      findings suggest the existence of substantial species-specific differences at the
      level of the biology of airway epithelial electrolyte transport, and potentially
      also in terms of CFTR structure/function.

PMID- 17008637
TI  - EGFR-activated signaling and actin remodeling regulate cyclic stretch-induced
      NRF2-ARE activation.
AB  - Cyclic stretch (CS) associated with mechanical ventilation (MV) can cause
      excessive alveolar and endothelial distention, resulting in lung injury and
      inflammation. Antioxidant enzymes (AOEs) play a major role in suppressing these
      effects. The transcription factor Nrf2, via the antioxidant response element
      (ARE), alleviates pulmonary toxicant- and oxidant-induced oxidative stress by up
      regulating the expression of several AOEs. Although gene expression profiling has
      revealed the induction of AOEs in the lungs of rodents exposed to MV, the
      mechanisms by which mechanical forces, such as CS, regulate the activation of
      Nrf2-dependent ARE-transcriptional responses are poorly understood. To mimic
      mechanical stress associated with MV, we have cultured pulmonary alveolar
      epithelial and endothelial cells on collagen I-coated BioFlex plates and
      subjected them to CS. CS exposure stimulated ARE-driven transcriptional responses
      and subsequent AOE expression. Ectopic expression of a dominant-negative Nrf2
      suppressed the CS-stimulated ARE-driven responses. Our findings suggest that
      actin remodeling is necessary but not sufficient for high-level CS-induced ARE
      activation in both epithelial and endothelial cells. We also found that
      inhibition of EGFR activity by a pharmacologic agent ablated the CS-induced ARE
      transcriptional response in both cell types. Additional studies revealed that
      amphiregulin, an EGFR ligand, regulates this process. We further demonstrated
      that the PI3K-Akt pathway acts as the downstream effector of EGFR and regulates
      CS-induced ARE-activation in an oxidative stress-dependent manner. Collectively,
      these novel findings suggest that EGFR-activated signaling and actin remodeling
      act in concert to regulate the CS-induced Nrf2-ARE transcriptional response and
      subsequent AOE expression.

PMID- 17008638
TI  - Superoxide dismutase improves oxygenation and reduces oxidation in neonatal
      pulmonary hypertension.
AB  - RATIONALE: Hyperoxic ventilation in the management of persistent pulmonary
      hypertension of the newborn (PPHN) can result in the formation of reactive oxygen
      species, such as superoxide anions, which can inactivate nitric oxide (NO) and
      cause vasoconstriction and oxidation. OBJECTIVE: To compare the effect of
      intratracheal recombinant human superoxide dismutase (rhSOD) and/or inhaled NO
      (iNO) on systemic oxygenation, contractility of pulmonary arteries (PAs), and
      lung reactive oxygen species (isoprostane, 3-nitrotyrosine) levels in neonatal
      lambs with PPHN. METHODS: Six newborn lambs with PPHN (induced by antenatal
      ductal ligation) were killed at birth. Twenty-six PPHN lambs were ventilated for
      24 h with 100% O(2) alone (n = 6) or O(2) combined with rhSOD (5 mg/kg
      intratracheally) at birth (n = 4), rhSOD at 4 h of age (n = 5), iNO (20 ppm, n =
      5), or rhSOD + iNO (n = 6). Contraction responses of fifth-generation PAs to
      norepinephrine and KCl, lung isoprostane levels, and 3-nitrotyrosine fluorescent
      intensity were measured. RESULTS: Systemic oxygenation was impaired in PPHN lambs
      and significantly improved (up to threefold) in both rhSOD groups with or without
      iNO. Oxygenation improved more rapidly with the combination of rhSOD + iNO
      compared with either intervention alone. Norepinephrine- and KCl-induced
      contractions and lung isoprostane levels were significantly increased by 100%
      O(2) compared with nonventilated newborn lambs with PPHN. Both rhSOD and iNO
      mitigated the increased PA contraction response and lung isoprostane levels.
      Intratracheal rhSOD decreased the enhanced lung 3-nitrotyrosine fluorescence
      observed with iNO therapy. CONCLUSION: Intratracheal rhSOD and/or iNO rapidly
      increase oxygenation and reduce both vasoconstriction and oxidation in newborn
      lambs with PPHN. This has important implications for clinical trials of rhSOD and
      iNO in newborn infants with PPHN.

PMID- 17008639
TI  - Cigarette smoke drives small airway remodeling by induction of growth factors in
      the airway wall.
AB  - BACKGROUND: Small airway remodeling (SAR) is an important cause of airflow
      obstruction in cigarette smokers with chronic obstructive pulmonary disease, but
      the pathogenesis of SAR is not understood. OBJECTIVE: To determine whether smoke
      causes production of profibrotic growth factors in the airway wall. METHODS: We
      exposed C57Bl/6 mice to cigarette smoke for up to 6 mo and examined growth
      factor/procollagen gene expression in laser-capture microdissected small airways
      by real-time reverse transcription-polymerase chain reaction. RESULTS: With a
      single smoke exposure, increases in procollagen, connective tissue growth factor
      (CTGF), transforming growth factor (TGF)-beta(1), platelet-derived growth factor
      (PDGF)-A and -B expression were seen 2 h after the start of smoking and declined
      to baseline by 24 h. With repeated exposures and at killing of animals 24 h after
      the last exposure, increases in procollagen, CTGF, PDGF-B, and (minimally) PDGF-A
      expression persisted through 1 wk, 1 mo, and 6 mo. TGF-beta(1) gene expression
      declined over time; however, increased immunochemical staining for phopho-Smad 2
      was present at all time points, indicating continuing TGF-beta downstream
      signaling. Morphometric analysis showed that the small airways in smoke-exposed
      mice had more collagen at 6 mo. CONCLUSIONS: These findings suggest that smoke
      can induce growth factor and procollagen production in small airways in a time
      frame that initially is too short for a significant inflammatory response and
      that profibrotic growth factor and procollagen gene expression become self
      sustaining with repeated smoke exposures. These results imply that the
      pathogenesis of and possible treatment approaches to emphysema and small airway
      remodeling might be quite different.

PMID- 17008640
TI  - Chronic rhinoviral infection in lung transplant recipients.
AB  - RATIONALE: Lung transplant recipients are particularly at risk of complications
      from rhinovirus, the most frequent respiratory virus circulating in the
      community. OBJECTIVES: To determine whether lung transplant recipients can be
      chronically infected by rhinovirus and the potential clinical impact. METHODS: We
      first identified an index case, in which rhinovirus was isolated repeatedly, and
      conducted detailed molecular analysis to determine whether this was related to a
      unique strain or to re-infection episodes. Transbronchial biopsies were used to
      assess the presence of rhinovirus in the lung parenchyma. The incidence of
      chronic rhinoviral infections and potential clinical impact was assessed
      prospectively in a cohort of 68 lung transplant recipients during 19 mo by
      screening of bronchoalveolar lavages. MEASUREMENTS AND MAIN RESULTS: We describe
      3 lung transplant recipients with graft dysfunctions in whom rhinovirus was
      identified by reverse transcriptase-polymerase chain reaction in upper and lower
      respiratory specimens over a 12-mo period. In two cases, rhinovirus was
      repeatedly isolated in culture. The persistence of a unique strain in each case
      was confirmed by sequence analysis of the 5'NCR and VP1 gene. In the index case,
      rhinovirus was detected in the lower respiratory parenchyma. In the cohort of
      lung transplant recipients, rhinoviral infections were documented in
      bronchoalveolar lavage specimens of 10 recipients, and 2 presented with a
      persistent infection. CONCLUSIONS: Rhinoviral infection can be persistent in lung
      transplant recipients with graft dysfunction, and the virus can be detected in
      the lung parenchyma. Given the potential clinical impact, chronic rhinoviral
      infection needs to be considered in lung transplant recipients.

PMID- 17008641
TI  - Lung tissue engineering technique with adipose stromal cells improves surgical
      outcome for pulmonary emphysema.
AB  - RATIONALE AND OBJECTIVES: Hepatocyte growth factor (HGF) is a potent regenerative
      factor generated after a lung injury, and HGF supplementation after surgical
      reduction has been shown to enhance compensatory growth in remnant lungs and
      improve pathophysiologic conditions in a rat model of emphysema. Adipose tissue
      derived stromal cells (ASCs) produce a large amount of angiogenic factors,
      including HGF. After lung volume reduction surgery (LVRS), we treated rats by
      implanting HGF-secreting ASCs with a scaffold onto the remnant lung tissue to
      determine the usefulness of this technique for treating respiratory dysfunction.
      METHODS AND MAIN RESULTS: Cells were isolated from rat inguinal adipose tissue
      and characterized by flow cytometry. ASCs were cultured on a polyglycolic acid
      felt sheet as a sealant material, and were shown to secrete significantly greater
      amounts of HGF than other angiogenic factors. Next, ASCs on polyglycolic acid
      felt sheets were used to cover the cut edge of the remaining lungs after LVRS for
      emphysema in rats. One week after implantation of the ASCs, both alveolar and
      vascular regeneration were significantly accelerated as compared with the rats
      that underwent LVRS alone. Consequently, gas exchange and exercise tolerance were
      also significantly restored, with these good results persisting for more than 1
      mo. CONCLUSIONS: The present findings demonstrate the therapeutic potential of
      cell therapy using ASCs with a scaffold for selective delivery of HGF to remnant
      lungs, which resulted in enhancement of compensatory growth, after surgical
      resection. This approach may provide a new strategy for lung tissue engineering
      to improve LVRS outcome.

PMID- 17008642
TI  - Incidence of chronic obstructive pulmonary disease in a cohort of young adults
      according to the presence of chronic cough and phlegm.
AB  - RATIONALE: The few prospective studies aimed at assessing the incidence of
      chronic obstructive pulmonary disease (COPD) in relation to the presence of
      chronic cough/phlegm have produced contrasting results. OBJECTIVES: To assess the
      incidence of COPD in a cohort of young adults and to test whether chronic
      cough/phlegm and dyspnea are independent predictors of COPD. METHODS: An
      international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal
      lung function (FEV(1)/FVC ratio >/= 70%) from 12 countries was followed from 1991
      2002 in the frame of the European Community Respiratory Health Survey II.
      Incident cases of COPD were those who had an FEV(1)/FVC ratio less than 70% at
      the end of the follow-up, but did not report having had a doctor diagnose asthma
      during the follow-up. MAIN RESULTS: The incidence rate of COPD was 2.8
      cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was
      an independent and statistically significant predictor of COPD (incidence rate
      ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and
      other potential confounders, whereas dyspnea was not associated with the disease
      (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both
      at baseline and at the follow-up had a nearly threefold-increased risk of
      developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44
      5.79). CONCLUSIONS: The incidence of COPD is substantial even in young adults.
      The presence of chronic cough/phlegm identifies a subgroup of subjects with a
      high risk of developing COPD, independently of smoking habits.

PMID- 17008643
TI  - Antioxidant treatment ameliorates respiratory syncytial virus-induced disease and
      lung inflammation.
AB  - RATIONALE: Respiratory syncytial virus (RSV) is a major cause of lower
      respiratory tract infection in children. No treatment has been shown to
      significantly improve the clinical outcome of patients with this infection.
      Recent evidence suggests that oxidative stress could play an important role in
      the pathogenesis of acute and chronic lung inflammatory diseases. We do not known
      whether RSV induces pulmonary oxidative stress and whether antioxidant treatment
      can modulate RSV-induced lung disease. OBJECTIVES: To investigate the effect of
      antioxidant administration on RSV-induced lung inflammation, clinical disease,
      and airway hyperreactivity (AHR). METHODS: BALB/c mice were infected with 10(7)
      plaque-forming units of RSV, in the presence or absence of orally administered
      butylated hydroxyanisole (BHA), an antioxidant. Malondialdehyde and 4
      hydroxynonenal were measured in bronchoalveoar lavage (BAL) by colorimetric
      assay. Cytokines and chemokines were measured in BAL by Bio-Plex and leukotrienes
      were measured by enzyme-linked immunosorbent assay. AHR to methacholine challenge
      was measured by whole-body plethysmography. RESULTS: BHA treatment significantly
      attenuated RSV-induced lung oxidative stress, as indicated by the decrease of
      malondialdehyde and 4-hydroxynonenal content in BAL of RSV-infected mice. RSV
      induced clinical illness and body weight loss were also reduced by BHA treatment,
      which inhibited neutrophil recruitment to the lung and significantly reduced
      pulmonary cytokine and chemokine production after RSV infection. Similarly,
      antioxidant treatment attenuated RSV-induced AHR. CONCLUSION: Modulation of
      oxidative stress represents a potential novel pharmacologic approach to
      ameliorate RSV-induced acute lung inflammation and potentially prevent long-term
      consequences associated with RSV infection, such as bronchial asthma.

PMID- 17008644
TI  - Adverse reactions to intravascular contrast agents.

PMID- 17008645
TI  - Bullying and harassment in medical schools.

PMID- 17008647
TI  - Criminal prosecution for HIV transmission.

PMID- 17008646
TI  - Congenital anomalies after treatment for infertility.

PMID- 17008648
TI  - Commissioning health education in primary care.

PMID- 17008650
TI  - US agency recommends opportunistic HIV testing.

PMID- 17008651
TI  - Better care for Michael Stone might still not have prevented the killings.

PMID- 17008654
TI  - More cancer patients in England are getting approved drugs.

PMID- 17008656
TI  - Uganda struggles to cope with rise in diabetes incidence.

PMID- 17008660
TI  - FDA warns US consumers not to eat spinach after E coli outbreak.

PMID- 17008661
TI  - Guidelines on drug trials in children go out for consultation.

PMID- 17008663
TI  - US Institute of Medicine calls for major changes at FDA.

PMID- 17008666
TI  - Two thirds of doctors in UK say the NHS could not cope with bird flu epidemic.

PMID- 17008668
TI  - Meningococcal disease and its management in children.

PMID- 17008669
TI  - Fever of unknown origin: case outcome.

PMID- 17008674
TI  - ABC of obesity. Assessment of obesity and its clinical implications.

PMID- 17008675
TI  - Parachute approach to evidence based medicine.

PMID- 17008676
TI  - Implications of ejection fraction value for trastuzumab.

PMID- 17008677
TI  - Are eligibility criteria for over the counter statins appropriate?

PMID- 17008678
TI  - Clinical examination for non-cephalic presentation: external cephalic version
      should be a maternity service quality indicator.

PMID- 17008679
TI  - Clinical examination for non-cephalic presentation: Royal College of Midwives'
      response to research.

PMID- 17008680
TI  - Extensively drug resistant tuberculosis: problem will get worse in South Africa
      unless poverty is alleviated.

PMID- 17008681
TI  - Extensively drug resistant tuberculosis: beware patients lost to follow-up.

PMID- 17008682
TI  - Detecting plagiarism: Google could be the way forward.

PMID- 17008683
TI  - Detecting plagiarism: meaning of citations is important.

PMID- 17008684
TI  - Detecting plagiarism: current quality control systems don't work.

PMID- 17008685
TI  - Phase I trials may not need to be viewed as extraordinarily different from other
      clinical research.

PMID- 17008686
TI  - Reversible posterior leukoencephalopathy syndrome induced by RAF kinase inhibitor
      BAY 43-9006.

PMID- 17008688
TI  - Changing face of small-cell lung cancer: real and artifact.

PMID- 17008689
TI  - Intraperitoneal chemotherapy in ovarian cancer remains experimental.

PMID- 17008690
TI  - Intraperitoneal therapy for ovarian cancer: a treatment ready for prime time.

PMID- 17008691
TI  - Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical
      pharmacogenomics arrives in cancer therapy.

PMID- 17008692
TI  - Changing epidemiology of small-cell lung cancer in the United States over the
      last 30 years: analysis of the surveillance, epidemiologic, and end results
      database.
AB  - PURPOSE: Small-cell lung cancer (SCLC) is a histologic subtype of lung cancer
      with a distinct biology and clinical course. It has been observed that the
      incidence of SCLC has been decreasing over the last several years. METHODS: We
      used the Surveillance, Epidemiologic, and End Results (SEER) database to
      determine the incidence of SCLC over the last 30 years. In addition, we sought to
      determine sex- and stage-based differences in the incidence and survival of SCLC
      among a proportion of reported cases of lung cancer over the last 30 years (1973
      to 2002). Joinpoint analyses were applied to test the trends in annual percentage
      change for statistical significance. RESULTS: The proportion of SCLC (among all
      lung cancer histologic types) decreased from 17.26% in 1986 to 12.95% in 2002. Of
      all patients with SCLC, the proportion of women with SCLC increased from 28% in
      1973% to 50% in 2002. A modest but statistically significant improvement in 2-
      and 5-year survival was noted among both limited-stage SCLC and extensive-stage
      SCLC cohorts during the study period. CONCLUSION: Our analysis indicates that the
      incidence of SCLC is decreasing in the United States, and only modest
      improvements have been seen in survival over the last 30 years. Possible
      explanations for the decreasing incidence include the decrease in the percentage
      of smokers and the change to low-tar filter cigarettes. Despite trends toward
      modest improvement in survival, the outcome remains very poor.

PMID- 17008693
TI  - Invisible barriers to clinical trials: the impact of structural, infrastructural,
      and procedural barriers to opening oncology clinical trials.
AB  - PURPOSE: To investigate the administrative barriers that impact the opening of
      clinical trials at the Vanderbilt-Ingram Cancer Center (VICC) and at VICC
      Affiliate Network (VICCAN) sites. METHODS: VICC, a National Cancer Institute
      designated comprehensive cancer center, and three VICCAN community practice sites
      were studied. Methodology used was identification and mapping of existing
      processes and analysis of historical timing data. RESULTS: At course granularity,
      the process steps required at VICC and VICCAN main office plus local sites are 20
      v 17 to 30 steps, respectively; this gap widens with finer granularity, with more
      than 110 v less than 60 steps, respectively. Approximately 50% of the steps are
      nonvalue added. For example, in the institutional review board (IRB) process,
      less than one third of the steps add value to the final protocol. The numbers of
      groups involved in the approval processes are 27 (VICC) and 6 to 14 (VICCAN home
      office and local sites). The median times to open a trial are 171 days (95% CI,
      158 to 182 days) for VICC and 191 days (95% CI, 119 to 269 days) for the VICCAN
      sites. Contrary to expectations, the time for IRB review and approval (median, 47
      days) is the fastest process compared with the scientific review committee review
      and approval (median, 70 days) and contracts and grants review (median, 78.5
      days). Opening a cooperative group clinical trial is significantly (P = .05) more
      rapid because they require fewer review steps. CONCLUSION: There are numerous
      opportunities to remove nonvalue-added steps and save time in opening clinical
      trials. With increasing numbers of new agents, fewer domestic principal
      investigators, and more companies off-shoring clinical trials, overcoming such
      barriers is of critical importance for maintenance of core oncology research
      capabilities in the United States.

PMID- 17008694
TI  - Processes to activate phase III clinical trials in a Cooperative Oncology Group:
      the Case of Cancer and Leukemia Group B.
AB  - PURPOSE: National Cancer Institute-sponsored cooperative oncology groups are
      major sponsors of phase III clinical trials, yet the time and steps required to
      design and activate such studies has not been well studied. We examine the
      processes and document the calendar time required to activate such studies opened
      by the Cancer and Leukemia Group B (CALGB). METHODS: Setup steps were documented
      by (1) interviewing CALGB headquarters and statistical center staff and committee
      chairs to discover the steps required to transit from concept development to
      final study activation, (2) reviewing procedure manuals, and (3) inspecting all
      study records, documents, and e-mails to identify any additional steps. Calendar
      time was collected for each major process. RESULTS: Thirteen phase III studies
      were activated by CALGB during the study period of May 2002 to May 2005. More
      than 370 distinct processes were required for study activation: 317 work steps,
      42 decision points, and 29 processing loops. Sixty-three percent of the decision
      points were outside CALGB. The complete process map measures 243.5" x 41" in 8
      point font. Median calendar days to activate a phase III study at CALGB was 580
      days (range, 295 to 1,248 days) from concept approval and 784 days (range, 537 to
      1,130 days) from initial conception of the study. CONCLUSION: Setup of a phase
      III study at a major cooperative oncology group is a complex and lengthy process,
      with the majority of decision points external to the cooperative group. To
      improve the activation process, research should to be directed toward both
      internal and external groups and processes.

PMID- 17008695
TI  - Clinical and pharmacologic study of the farnesyltransferase inhibitor tipifarnib
      in cancer patients with normal or mildly or moderately impaired hepatic function.
AB  - PURPOSE: This study explored the feasibility of treating patients with impaired
      hepatic function with tipifarnib. The safety profile, pharmacokinetics, and
      relationship between the pharmacokinetics and toxicities were evaluated. PATIENTS
      AND METHODS: Patients with mildly or moderately impaired hepatic function (Child
      Pugh classification) were treated with tipifarnib bid on days 1 to 5 of cycle 1.
      Further dosing was based on the individual day 5 pharmacokinetic data and
      absolute neutrophil count. For patients with normal hepatic function, tipifarnib
      was dosed on days 1 to 14, followed by 1 week of rest. For all patients, in
      subsequent cycles, tipifarnib was administered for 21 consecutive days out of
      every 28 days. RESULTS: Twenty-eight patients were included in the normal (n =
      16), mild (n = 9), and moderate (n = 3) impairment groups. The most important
      grade 3 to 4 hematologic toxicity was leukocytopenia/neutropenia, which was
      mostly observed in patients with moderate impairment. Common nonhematologic
      toxicities were fatigue, nausea, and vomiting. The pharmacokinetic data showed
      higher plasma concentrations of tipifarnib in patients with liver impairment
      compared with patients with normal hepatic function. CONCLUSION: In patients with
      mildly impaired hepatic function, tipifarnib can be administered safely at a
      starting dose of 200 mg bid, but it is not safe to treat patients with moderate
      hepatic impairment.

PMID- 17008696
TI  - Prognostic significance of nuclear receptor coactivator-3 overexpression in
      primary cutaneous melanoma.
AB  - PURPOSE: To assess the prognostic significance of nuclear receptor coactivator-3
      (NCOA3) overexpression in primary cutaneous melanoma. PATIENTS AND METHODS: NCOA3
      expression was assessed using immunohistochemical analysis of a melanoma tissue
      microarray (TMA) containing primary melanomas from 343 patients with defined
      histology and follow-up. The impact of the presence or absence of various
      prognostic factors on relapse-free survival (RFS) and disease-specific survival
      (DSS) of melanoma patients was assessed using Cox regression and Kaplan-Meier
      analysis. The impact of presence or absence of various factors on sentinel lymph
      node (SLN) metastasis was assessed using logistic regression analysis. RESULTS:
      Increasing degree of NCOA3 expression was significantly predictive of SLN
      metastasis (P = .013) and the mean number of SLN metastases (P = .031). Kaplan
      Meier analysis demonstrated a significant association between NCOA3
      overexpression and reduced RFS (P = .021) and DSS (P = .030). Logistic regression
      analysis revealed increasing degree of NCOA3 expression to be an independent
      predictor of SLN status (P = .017). Multivariate Cox regression analysis showed
      the independent impact of NCOA3 expression on RFS (P = .0095) and DSS (P = .021).
      NCOA3 was the most powerful factor predicting DSS, outperforming tumor thickness
      and ulceration. CONCLUSION: These results identify NCOA3 as a novel, independent
      marker of melanoma outcome, with a significant impact on SLN metastasis, RFS, and
      DSS.

PMID- 17008697
TI  - Long-term follow-up of high-dose methotrexate-based therapy with and without
      whole brain irradiation for newly diagnosed primary CNS lymphoma.
AB  - PURPOSE: We previously reported a series of patients treated with high-dose
      methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy.
      The purpose of this report is to update the initial results and provide long-term
      data regarding overall survival, patterns of relapse, and the risk of treatment
      related neurotoxicity. PATIENTS AND METHODS: Fifty-seven patients with an average
      age of 65 and median Karnofsky performance score of 70 were treated; all patients
      have been observed longitudinally with serial magnetic resonance imaging scans
      and neurologic examinations. RESULTS: The overall median survival was 51 months
      with a median follow-up of 115 months for surviving patients. Twenty-five
      patients relapsed or developed progressive disease; median progression-free
      survival was 129 months. Seventeen patients developed treatment-related
      neurotoxicity; all but one had received whole brain radiotherapy as a component
      of treatment. Seventy-four percent of patients younger than 60 years who received
      both MTX-based chemotherapy and whole brain radiotherapy were alive at last
      follow-up. Median survival for patients older than 60 years was 29 months
      regardless of whether or not they received whole brain radiotherapy. CONCLUSION:
      Long-term follow-up of our initial cohort confirms the observation of excellent
      overall survival, particularly for those patients younger than age 60 at
      diagnosis. For older patients, it appears to be reasonable to defer whole brain
      radiotherapy in an effort to minimize treatment-related neurotoxicity.

PMID- 17008698
TI  - Catheter-related deep venous thrombosis and other catheter complications in
      children with cancer.
AB  - PURPOSE: Asymptomatic deep vein thrombosis (DVT) is a complication of central
      venous catheter (CVC) use in children with cancer, but its clinical significance
      is not well defined. Children with CVCs commonly experience two other CVC-related
      complications: occlusion and infection. The aim of this study was to determine
      the frequency of these two complications and their association with DVT. PATIENTS
      AND METHODS: We conducted a retrospective cohort study of patients who were
      diagnosed with cancer. Data collected included number and type of catheter
      insertions, duration of use, reason for removal, associated catheter
      complications, and demographic information. RESULTS: Catheters were placed in 287
      patients for a total of 128,403 days (mean, 290 +/- 269 days/catheter). Of 21
      patients (7%) diagnosed with CVC-related DVT, only five had specific signs or
      symptoms. Nineteen (90%) of these 21 children had prior history of catheter
      occlusion, and 10 of the 19 also experienced infection. Ten children (48%) were
      not identified as having DVT until they had had multiple catheters with recurrent
      complications. Odds of having DVT were higher in patients who had a single
      catheter complicated by repeated occlusions (odds ratio [OR], 3.7; P = .001) or
      infection (OR, 2.2; P = .016). Patients experiencing both infection and occlusion
      were at 6.4 times (P < .0001) higher risk of developing DVT. CONCLUSION: Children
      with CVC-related DVT frequently have recurrent catheter complications.
      Unrecognized thrombosis may therefore be clinically important. Prospective
      studies are needed to determine if identification and treatment of occult DVT
      will prevent additional CVC-related complications and prolong the duration of
      catheter use.

PMID- 17008699
TI  - Do patients with localized prostate cancer treatment really want more aggressive
      treatment?
AB  - PURPOSE: Examine whether patients with prostate cancer choose the more aggressive
      of two radiotherapeutic options, whether this choice is reasoned, and what the
      determinants of the choice are. PATIENTS AND METHODS: One hundred fifty patients
      with primary prostate cancer (T(1-3)N(0)M(0)) were informed by means of a
      decision aid of two treatment options: radiotherapy with 70 Gy versus 74 Gy. The
      latter treatment is associated with more cure and more toxicity. The patients
      were asked whether they wanted to choose, and if so which treatment they
      preferred. They also assigned importance weights to the probability of various
      outcomes, such as survival, cure and adverse effects. Patients who wanted to
      choose their own treatment (n = 119) are described here. RESULTS: The majority of
      these patients (75%) chose the lower radiation dose. Their choice was highly
      consistent (P < or = .001), with the importance weights assigned to the
      probability of survival, cure (odds ratio [OR] = 6.7 and 6.9) and late GI and
      genitourinary adverse effects (OR = 0.1 and 0.2). The lower dose was chosen more
      often by the older patients, low-risk patients, patients without hormone
      treatment, and patients with a low anxiety or depression score. CONCLUSION: Most
      patients with localized prostate cancer prefer the lower radiation dose. Our
      findings indicate that many patients attach more weight to specific quality-of
      life aspects (eg, GI toxicity) than to improving survival. Treatment preferences
      of patients with localized prostate cancer can and should be involved in
      radiotherapy decision making.

PMID- 17008700
TI  - Early response evaluation in malignant pleural mesothelioma by positron emission
      tomography with [18F]fluorodeoxyglucose.
AB  - PURPOSE: Response evaluation with conventional criteria based on computed
      tomography (CT) is particularly challenging in malignant pleural mesothelioma
      (MPM) due to its diffuse pattern of growth. There is growing evidence that
      therapy-induced changes in tumor [(18)F]fluorodeoxyglucose (FDG) uptake as
      measured by positron emission tomography (PET) may predict response and patient
      outcome early in the course of treatment. PATIENTS AND METHODS: Patients with
      histologically proven MPM, not candidates to curative surgery, scheduled to
      undergo palliative chemotherapy with a pemetrexed-based regimen were eligible for
      this study. Patients were evaluated by FDG-PET and CT at baseline and after two
      cycles of therapy. A decrease of 25% or more in tumor FDG uptake as measured by
      standardized uptake value was defined as a metabolic response (MR). Best overall
      response from CT scans was determined according to previously published criteria.
      RESULTS: Twenty-two patients were included in the study, and 20 were assessable
      for early metabolic response with FDG-PET. Of these, eight were classified as
      responders (40%) and 12 as nonresponders (60%). Early MR was significantly
      correlated to median time-to-tumor progression (TTP) with a median TTP for
      metabolic responders of 14 months versus 7 months for nonresponders (P = .02). No
      correlation was found between TTP and radiologic response evaluated by CT.
      Patients with a MR had a trend toward longer overall survival. CONCLUSION: The
      use of MR evaluated by FDG-PET in the assessment of treatment efficacy in MPM
      appears promising. Our observations need to be validated in a larger prospective
      series.

PMID- 17008701
TI  - Genomic prediction of locoregional recurrence after mastectomy in breast cancer.
AB  - PURPOSE: This study aims to explore gene expression profiles that are associated
      with locoregional (LR) recurrence in breast cancer after mastectomy. PATIENTS AND
      METHODS: A total of 94 breast cancer patients who underwent mastectomy between
      1990 and 2001 and had DNA microarray study on the primary tumor tissues were
      chosen for this study. Eligible patient should have no evidence of LR recurrence
      without postmastectomy radiotherapy (PMRT) after a minimum of 3-year follow-up (n
      = 67) and any LR recurrence (n = 27). They were randomly split into training and
      validation sets. Statistical classification tree analysis and proportional
      hazards models were developed to identify and validate gene expression profiles
      that relate to LR recurrence. RESULTS: Our study demonstrates two sets of gene
      expression profiles (one with 258 genes and the other 34 genes) to be of
      predictive value with respect to LR recurrence. The overall accuracy of the
      prediction tree model in validation sets is estimated 75% to 78%. Of patients in
      validation data set, the 3-year LR control rate with predictive index more than
      0.8 derived from 34-gene prediction models is 91%, and predictive index 0.8 or
      less is 40% (P = .008). Multivariate analysis of all patients reveals that
      estrogen receptor and genomic predictive index are independent prognostic factors
      that affect LR control. CONCLUSION: Using gene expression profiles to develop
      prediction tree models effectively identifies breast cancer patients who are at
      higher risk for LR recurrence. This gene expression-based predictive index can be
      used to select patients for PMRT.

PMID- 17008702
TI  - Magnetic resonance imaging captures the biology of ductal carcinoma in situ.
AB  - PURPOSE: Magnetic resonance imaging (MRI) is an important tool for characterizing
      invasive breast cancer but has proven to be more challenging in the setting of
      ductal carcinoma in situ (DCIS). We investigated whether MRI features of DCIS
      reflect differences in biology and pathology. PATIENTS AND METHODS: Forty five of
      100 patients with biopsy-proven DCIS who underwent MRI and had sufficient tissue
      to be characterized by pathologic (nuclear grade, presence of comedo necrosis,
      size, and density of disease) and immunohistochemical (IHC) findings
      (proliferation, Ki67; angiogenesis, CD34; and inflammation, CD68). Pathology and
      MRI features (enhancement patterns, distribution, size, and density) were
      analyzed using pairwise and canonical correlations. RESULTS: Histopathologic and
      IHC variables correlated with MRI features (r = 0.73). The correlation was
      largely due to size, density (by either MRI or pathology), and inflammation (P <
      .05). Most small focal masses were estrogen receptor-positive. MRI enhancement
      patterns that were clumped were more likely than heterogeneous patterns to be
      high-grade lesions. Homogenous lesions were large, high grade, and rich in
      macrophages. Presence of comedo necrosis and size could be distinguished on MRI
      (P < .05). MRI was most likely to over-represent the size of less dense, diffuse
      DCIS lesions. CONCLUSION: The heterogeneous presentation of DCIS on MRI reflects
      underlying histopathologic differences.

PMID- 17008703
TI  - The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast
      cancer.
AB  - PURPOSE: We previously identified three genes, HOXB13, IL17BR and CHDH, and the
      HOXB13:IL17BR ratio index in particular, that strongly predicted clinical outcome
      in breast cancer patients receiving tamoxifen monotherapy. Confirmation in larger
      independent patient cohorts was needed to fully validate their clinical utility.
      PATIENTS AND METHODS: Expression of HOXB13, IL17BR, CHDH, estrogen receptor (ER)
      and progesterone receptor (PR) were quantified by real-time polymerase chain
      reaction in 852 formalin-fixed, paraffin-embedded primary breast cancers from 566
      untreated and 286 tamoxifen-treated breast cancer patients. Gene expression and
      clinical variables were analyzed for association with relapse-free survival (RFS)
      by Cox proportional hazards regression models. RESULTS: ER and PR mRNA
      measurements were in close agreement with immunohistochemistry. In the entire
      cohort, expression of HOXB13 was associated with shorter RFS (P = .008), and
      expression of IL17BR and CHDH was associated with longer RFS (P < .0001 for
      IL17BR and P = .0002 for CHDH). In ER+ patients, the HOXB13:IL17BR index
      predicted clinical outcome independently of treatment, but more strongly in node
      negative patients. In multivariate analysis of the ER+ node-negative subgroup
      including age, PR status, tumor size, S phase fraction, and tamoxifen treatment,
      the two-gene index remained a significant predictor of RFS (hazard ratio = 3.9;
      95% CI, 1.5 to 10.3; P = .007). CONCLUSION: This tumor bank study demonstrated
      HOXB13:IL17BR index is a strong independent prognostic factor for ER+ node
      negative patients irrespective of tamoxifen therapy.

PMID- 17008704
TI  - Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin
      in T3-4 rectal cancers: results of FFCD 9203.
AB  - PURPOSE: In 1992, preoperative radiotherapy was considered in France as the
      standard treatment for T3-4 rectal cancers. The present randomized trial compares
      preoperative radiotherapy with chemoradiotherapy. PATIENTS AND METHODS: Patients
      were eligible if they presented a resectable T3-4, Nx, M0 rectal adenocarcinoma
      accessible to digital rectal examination. Preoperative radiotherapy with 45 Gy in
      25 fractions during 5 weeks was delivered. Concurrent chemotherapy with
      fluorouracil 350 mg/m2/d during 5 days, together with leucovorin, was
      administered during the first and fifth week in the experimental arm. Surgery was
      planned 3 to 10 weeks after the end of radiotherapy. All patients should receive
      adjuvant chemotherapy with the same fluorouracil/leucovorin regimen. The primary
      end point of the trial was overall survival. RESULTS: A total of 733 patients
      were eligible. Grade 3 or 4 acute toxicity was more frequent with
      chemoradiotherapy (14.6% v 2.7%; P < .05). There was no difference in sphincter
      preservation. Complete sterilization of the operative specimen was more frequent
      with chemoradiotherapy (11.4% v 3.6%; P < .05). The 5-year incidence of local
      recurrence was lower with chemoradiotherapy (8.1% v 16.5%; P < .05). Overall 5
      year survival in the two groups did not differ. CONCLUSION: Preoperative
      chemoradiotherapy despite a moderate increase in acute toxicity and no impact on
      overall survival significantly improves local control and is recommended for T3
      4, N0-2, M0 adenocarcinoma of the middle and distal rectum.

PMID- 17008705
TI  - Prospective evaluation of clonal evolution during long-term follow-up of patients
      with untreated early-stage chronic lymphocytic leukemia.
AB  - PURPOSE: Retrospective studies suggest cytogenetic abnormalities detected by
      interphase fluorescent in situ hybridization (FISH) can identify patients with
      chronic lymphocytic leukemia (CLL) who will experience a more aggressive disease
      course. Other studies suggest that patients may acquire chromosome abnormalities
      during the course of their disease. There are minimal prospective data on the
      clinical utility of the widely used hierarchical FISH prognostic categories in
      patients with newly diagnosed early-stage CLL or the frequency of clonal
      evolution as determined by interphase FISH. PATIENTS AND METHODS: Between 1994
      and 2002, we enrolled 159 patients with previously untreated CLL (83% Rai stage
      0/I) on a prospective trial evaluating clonal evolution by FISH. Patients
      provided baseline and follow-up specimens for FISH testing during 2 to 12 years.
      RESULTS: Chromosomal abnormalities detected by FISH at study entry predicted
      overall survival. Eighteen patients experienced clonal evolution during follow
      up. The rate of clonal evolution increased with duration of follow-up with only
      one occurrence in the first 2 years (n = 71; 1.4%) but 17 occurrences (n = 63;
      27%) among patients tested after 5+ years. Clonal evolution occurred among 10% of
      ZAP-70-negative and 42% of ZAP-70-positive patients at 5+ years (P = .008).
      CONCLUSION: This clinical trial confirms prospectively that cytogenetic
      abnormalities detected by FISH can predict overall survival for CLL patients at
      the time of diagnosis, but also suggests that many patients acquire new
      abnormalities during the course of their disease. Patients with higher ZAP-70
      expression may be more likely to experience such clonal evolution. These findings
      have important implications for both clinical management and trials of early
      treatment for patients with high-risk, early-stage CLL.

PMID- 17008706
TI  - ASCO/SSO review of current role of risk-reducing surgery in common hereditary
      cancer syndromes.
AB  - Although the etiology of solid cancers is multifactorial, with environmental and
      genetic factors playing a variable role, a significant portion of the burden of
      cancer is accounted for by a heritable component. Increasingly, the heritable
      component of cancer predispositions has been linked to mutations in specific
      genes, and clinical interventions have been formulated for mutation carriers
      within affected families. The primary interventions for mutations carriers for
      highly penetrant syndromes such as multiple endocrine neoplasias, familial
      adenomatous polyposis, hereditary nonpolyposis colon cancer, and hereditary
      breast and ovarian cancer syndromes are primarily surgical. For that reason, the
      American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology
      (SSO) have undertaken an educational effort within the oncology community. A
      joint ASCO/SSO Task Force was charged with presenting an educational symposium on
      the surgical management of hereditary cancer syndromes at the annual ASCO and SSO
      meetings, resulting in an educational position article on this topic. Both the
      content of the symposium and the article were developed as a consensus statement
      by the Task Force, with the intent of summarizing the current standard of care.
      This article is divided into four sections addressing breast, colorectal, ovarian
      and endometrial cancers, and multiple endocrine neoplasia. For each, a brief
      introduction on the genetics and natural history of the disease is provided,
      followed by a detailed description of modern surgical approaches, including a
      description of the clinical and genetic indications and timing of prophylactic
      surgery, and the efficacy of prophylactic surgery when known. Although a number
      of recent reviews have addressed the role of genetic testing for cancer
      susceptibility, including the richly illustrated Cancer Genetics and Cancer
      Predisposition Testing curriculum by the ASCO Cancer Genetics Working Group
      (available through http://www.asco.org), this article focuses on the issues
      surrounding the why, how, and when of surgical prophylaxis for inherited forms of
      cancer. This is a complex process, which requires a clear understanding of the
      natural history of the disease and variance of penetrance, a realistic
      appreciation of the potential benefit and risk of a risk-reducing procedure in a
      potentially otherwise healthy individual, the long-term sequelae of such surgical
      intervention, as well as the individual patient and family's perception of
      surgical risk and anticipated benefit.

PMID- 17008707
TI  - The discussion group for mortals.

PMID- 17008708
TI  - Role of neoadjuvant chemotherapy in rectal cancer: interpretation of the EXPERT
      study.

PMID- 17008709
TI  - Raltitrexed and pemetrexed studies in mesothelioma have not shown improved
      quality of life nor prolonged survival compared with effective pleurodesis with
      thoracoscopic talc poudrage.

PMID- 17008710
TI  - Are dose-finding studies still necessary when targeted therapy is associated with
      chemotherapy?

PMID- 17008711
TI  - Problems with the randomized discontinuation design.

PMID- 17008712
TI  - The origami of thioredoxin-like folds.
AB  - Origami is the Japanese art of folding a piece of paper into complex shapes and
      forms. Much like origami of paper, Nature has used conserved protein folds to
      engineer proteins for a particular task. An example of a protein family, which
      has been used by Nature numerous times, is the thioredoxin superfamily. Proteins
      in the thioredoxin superfamily are all structured with a beta-sheet core
      surrounded with alpha-helices, and most contain a canonical CXXC motif. The
      remarkable feature of these proteins is that the link between them is the fold;
      however, their reactivity is different for each member due to small variations in
      this general fold as well as their active site. This review attempts to unravel
      the minute differences within this protein family, and it also demonstrates the
      ingenuity of Nature to use a conserved fold to generate a diverse collection of
      proteins to perform a number of different biochemical tasks.

PMID- 17008713
TI  - Characterization of the five novel Ly-6 superfamily members encoded in the MHC,
      and detection of cells expressing their potential ligands.
AB  - Lymphocyte Antigen 6 (Ly-6) superfamily members are cysteine-rich, generally GPI
      anchored cell surface proteins, which have definite or putative immune related
      roles. There are 27 members of this family described so far in the human genome
      and 37 in the mouse. Five of them are clustered in the class III region of the
      human and mouse MHCs. Following computational analyses, we functionally
      characterized the encoded proteins by creating epitope-tagged fusion constructs
      to determine molecular weight, complex formation, subcellular localization, post
      translational modifications and ligand binding. We found that all human and mouse
      proteins were glycosylated, and most could form part of larger complexes. Human
      and mouse Ly6G6c and Ly6G6d, and mouse Ly6g6e were found to be GPI-anchored cell
      surface proteins, highly expressed at the leading edges of cells, on filopodia,
      which are normally involved in cell adhesion and migration. However, analysis of
      Ly6G5c and Ly6G5b indicated that they are potentially secreted proteins. Our
      results indicate that there are two subclusters of related Ly-6 proteins in this
      region of the MHC, with Ly6G6c, Ly6G6d, and Ly6G6e forming one and Ly6G5c and
      Ly6G5b forming another. In addition, by FACS analysis we have found that the
      potential ligands for human LY6G6C, LY6G6D, and LY6G5C are expressed on K562
      cells, an undifferentiated megakaryocyte cell line, indicating a potential role
      in hematopoietic cell differentiation. This characterization of the five MHC
      class III region Ly-6 family members is of great relevance, as they represent 18%
      of the human Ly-6 protein family and 50% of the secreted ones.

PMID- 17008714
TI  - Methods for the accurate estimation of confidence intervals on protein folding
      phi-values.
AB  - Phi-values provide an important benchmark for the comparison of experimental
      protein folding studies to computer simulations and theories of the folding
      process. Despite the growing importance of phi measurements, however, formulas to
      quantify the precision with which phi is measured have seen little significant
      discussion. Moreover, a commonly employed method for the determination of
      standard errors on phi estimates assumes that estimates of the changes in free
      energy of the transition and folded states are independent. Here we demonstrate
      that this assumption is usually incorrect and that this typically leads to the
      underestimation of phi precision. We derive an analytical expression for the
      precision of phi estimates (assuming linear chevron behavior) that explicitly
      takes this dependence into account. We also describe an alternative method that
      implicitly corrects for the effect. By simulating experimental chevron data, we
      show that both methods accurately estimate phi confidence intervals. We also
      explore the effects of the commonly employed techniques of calculating phi from
      kinetics estimated at non-zero denaturant concentrations and via the assumption
      of parallel chevron arms. We find that these approaches can produce significantly
      different estimates for phi (again, even for truly linear chevron behavior),
      indicating that they are not equivalent, interchangeable measures of transition
      state structure. Lastly, we describe a Web-based implementation of the above
      algorithms for general use by the protein folding community.

PMID- 17008715
TI  - Association of putative concave protein-binding sites with the fluctuation
      behavior of residues.
AB  - Here, we propose a binding site prediction method based on the high frequency end
      of the spectrum in the native state of the protein structural dynamics. The
      spectrum is obtained using an elastic network model (GNM). High frequency
      vibrating (HFV) residues are determined from the fastest modes dynamics. HFV
      residue clusters and the associated surface patch residues are tested for their
      likelihood to locate at the binding interfaces using two different data sets, the
      Benchmark Set of mainly enzymes and antigen/antibodies and the Cluster Set of
      more diverse structures. The binding interface is identified to be within 7.5 A
      of the HFV residue clusters in the Benchmark Set and Cluster Set, for 77% and 70%
      of the structures, respectively. The success rate increases to 88% and 84%,
      respectively, by using the surface patches. The results suggest that concave
      binding interfaces, typically those of enzyme-binding sites, are enriched by the
      HFV residues. Thus, we expect that the association of HFV residues with the
      interfaces is mostly for enzymes. If, however, a binding region has invaginations
      and cavities, as in some of the antigen/antibodies and in cases in the Cluster
      data set, we expect it would be detected there too. This implies that binding
      sites possess several (inter-related) properties such as cavities, high packing
      density, conservation, and disposition for hotspots at binding surfaces. It
      further suggests that the high frequency vibrating residue-based approach is a
      potential tool for identification of regions likely to serve as protein-binding
      sites. The software is available at http://www.prc.boun.edu.tr/PRC/software.html.

PMID- 17008716
TI  - Elucidation of the mechanism of the regulatory function of the Ig1 module of the
      fibroblast growth factor receptor 1.
AB  - The extracellular part of the fibroblast growth factor (FGF) receptor (FGFR)
      consists of up to three Ig modules (Ig1-Ig3), in which the Ig2 and Ig3 modules
      determine affinity and specificity for FGF and heparin. The FGFR isoforms lacking
      the Ig1 module have higher affinity for FGF and heparin than the triple Ig-module
      isoforms, suggesting that the Ig1 module is involved in the regulation of the
      FGFR-ligand interaction. We show here by surface plasmon resonance and NMR
      analyses that the Ig1 module binds to the Ig2 module, and identify by NMR the
      binding sites involved in the Ig1-Ig2 interaction. The identified binding site in
      the Ig2 module was found to be in the area of the FGF-Ig2 and Ig2-heparin contact
      sites, thus providing direct structural evidence that the Ig1 module functions as
      a competitive autoinhibitor of the FGFR-ligand interaction. Furthermore, the Ig1
      binding site of the Ig2 module overlaps the Ig2-Ig2 contact site. This suggests
      that the function of the Ig1 module is not only regulation of the FGFR-ligand
      binding affinity but also prevention of spontaneous FGFR dimerization (through a
      direct Ig2-Ig2 interaction) in the absence of FGF.

PMID- 17008717
TI  - Molecular dynamics and in vitro analysis of Connexin43: A new 14-3-3 mode-1
      interacting protein.
AB  - The interaction of cellular proteins with the gap junction protein Connexin43
      (Cx43) is thought to form a dynamic scaffolding complex that functions as a
      platform for the assembly of signaling, structural, and cytoskeletal proteins. A
      high stringency Scansite search of rat Cx43 identified the motif containing
      Ser373 (S373) as a 14-3-3 binding site. The S373 motif and the second best mode-1
      motif, containing Ser244 (S244), are conserved in rat, mouse, human, chicken, and
      bovine, but not in Xenopus or zebrafish Cx43. Docking studies of a mouse/rat 14-3
      3 homology model with the modeled phosphorylated S373 or S244 peptide ligands or
      their serine-to-alanine mutants, S373A or S244A, revealed that the pS373 motif
      facilitated a greater number of intermolecular contacts than the pS244 motif,
      thus supporting a stronger 14-3-3 binding interaction with the pS373 motif. The
      alanine substitution also reduced more than half the number of intermolecular
      contacts between 14-3-3 and the S373 motif, emphasizing the phosphorylation
      dependence of this interaction. Furthermore, the ability of the wild-type or the
      S244A GST-Cx43 C-terminal fusion protein, but not the S373A fusion protein, to
      interact with either 14-3-3 or 14-3-3zeta in GST pull-down experiments clearly
      demonstrated that the S373 motif mediates the direct interaction between Cx43 and
      14-3-3 proteins. Blocking growth factor-induced Akt activation and presumably any
      Akt-mediated phosphorylation of the S373 motif in ROSE 199 cells did not prevent
      the down-regulation of Cx43-mediated cell-cell communication, suggesting that an
      Akt-mediated interaction with 14-3-3 was not involved in the disruption of Cx43
      function.

PMID- 17008718
TI  - Combinatorial Domain Hunting: An effective approach for the identification of
      soluble protein domains adaptable to high-throughput applications.
AB  - Exploitation of potential new targets for drug and vaccine development has an
      absolute requirement for multimilligram quantities of soluble protein. While
      recombinant expression of full-length proteins is frequently problematic, high
      yield soluble expression of functional subconstructs is an effective alternative,
      so long as appropriate termini can be identified. Bioinformatics localizes
      domains, but doesn't predict boundaries with sufficient accuracy, so that
      subconstructs are typically found by trial and error. Combinatorial Domain
      Hunting (CDH) is a technology for discovering soluble, highly expressed
      constructs of target proteins. CDH combines unbiased, finely sampled gene
      fragment libraries, with a screening protocol that provides "holistic" readout of
      solubility and yield for thousands of protein fragments. CDH is free of the
      "passenger solubilization" and out-of-frame translational start artifacts of
      fusion-protein systems, and hits are ready for scale-up expression. As a proof of
      principle, we applied CDH to p85alpha, successfully identifying soluble and
      highly expressed constructs encapsulating all the known globular domains, and
      immediately suitable for downstream applications.

PMID- 17008719
TI  - Three-dimensional structure and ligand interactions of the low molecular weight
      protein tyrosine phosphatase from Campylobacter jejuni.
AB  - A putative low molecular weight protein tyrosine phosphatase (LMW-PTP) was
      identified in the genome sequence of the bacterial pathogen, Campylobacter
      jejuni. This novel gene, cj1258, has sequence homology with a distinctive class
      of phosphatases widely distributed among prokaryotes and eukaryotes. We report
      here the solution structure of Cj1258 established by high-resolution NMR
      spectroscopy using NOE-derived distance restraints, hydrogen bond data, and
      torsion angle restraints. The three-dimensional structure consists of a central
      four-stranded parallel beta-sheet flanked by five alpha-helices, revealing an
      overall structural topology similar to those of the eukaryotic LMW-PTPs, such as
      human HCPTP-A, bovine BPTP, and Saccharomyces cerevisiae LTP1, and to those of
      the bacterial LMW-PTPs MPtpA from Mycobacterium tuberculosis and YwlE from
      Bacillus subtilis. The active site of the enzyme is flexible in solution and
      readily adapts to the binding of ligands, such as the phosphate ion. An NMR-based
      screen was carried out against a number of potential inhibitors and activators,
      including phosphonomethylphenylalanine, derivatives of the cinnamic acid, 2
      hydroxy-5-nitrobenzaldehyde, cinnamaldehyde, adenine, and hypoxanthine. Despite
      its bacterial origin, both the three-dimensional structure and ligand-binding
      properties of Cj1258 suggest that this novel phosphatase may have functional
      roles close to those of eukaryotic and mammalian tyrosine phosphatases. The three
      dimensional structure along with mapping of small-molecule binding will be
      discussed in the context of developing high-affinity inhibitors of this novel LMW
      PTP.

PMID- 17008720
TI  - Trapping the tetrahedral intermediate in the alkaline phosphatase reaction by
      substitution of the active site serine with threonine.
AB  - We report here the construction of a mutant version of Escherichia coli alkaline
      phosphatase (AP) in which the active site Ser was replaced by Thr (S102T), in
      order to investigate whether the enzyme can utilize Thr as the nucleophile and
      whether the rates of the critical steps in the mechanism are altered by the
      substitution. The mutant AP with Thr at position 102 exhibited an approximately
      4000-fold decrease in k(cat) along with a small decrease in Km. The decrease in
      catalytic efficiency of approximately 2000-fold was a much smaller drop than that
      observed when Ala or Gly were substituted at position 102. The mechanism by which
      Thr can substitute for Ser in AP was further investigated by determining the X
      ray structure of the S102T enzyme in the presence of the Pi (S102T_Pi), and after
      soaking the crystals with substrate (S102T_sub). In the S102T_Pi structure, the
      Pi was coordinated differently with its position shifted by 1.3 A compared to the
      structure of the wild-type enzyme in the presence of Pi. In the S102T_sub
      structure, a covalent Thr-Pi intermediate was observed, instead of the expected
      bound substrate. The stereochemistry of the phosphorus in the S102T_sub structure
      was inverted compared to the stereochemistry in the wild-type structure, as would
      be expected after the first step of a double in-line displacement mechanism. We
      conclude that the S102T mutation resulted in a shift in the rate-determining step
      in the mechanism allowing us to trap the covalent intermediate of the reaction in
      the crystal.

PMID- 17008722
TI  - Engineered zinc-binding sites confirm proximity and orientation of transmembrane
      helices I and III in the human serotonin transporter.
AB  - The human serotonin transporter (hSERT) regulates neurotransmission by removing
      released serotonin (5-HT) from the synapse. Previous studies identified residues
      in SERT transmembrane helices (TMHs) I and III as interaction sites for
      substrates and antagonists. Despite an abundance of data supporting a 12-TMH
      topology, the arrangement of the TMHs in SERT and other biogenic amine
      transporters remains undetermined. A high-resolution structure of a bacterial
      leucine transporter that demonstrates homology with SERT has been reported, thus
      providing the basis for the development of a SERT model. Zn2+-binding sites have
      been utilized in transporters and receptors to define experimentally TMH
      proximity. Focusing on residues near the extracellular ends of hSERT TMHs I and
      III, we engineered potential Zn2+-binding sites between V102 or W103 (TMH I) and
      I179-L184 (TMH III). Residues were mutated to either histidine or cysteine. TMH
      I/III double mutants were constructed from functional TMH I mutants, and Zn2+
      sensitivity was assessed. Dose-response assays suggest an approximately twofold
      increase in sensitivity to Zn2+ inhibition at the hSERT V102C/M180C and
      approximately fourfold at the V102C/I179C mutant compared to the hSERT V102C
      single mutant. We propose that the increased sensitivity to Zn2+ confirms the
      proximity and the orientation of TMHs I and III in the membrane. Homology
      modeling of the proposed Zn2+-binding sites using the coordinates of the Aquifex
      aeolicus leucine transporter structure provided a structural basis for
      interpreting the results and developing conclusions.

PMID- 17008721
TI  - Altered dynamics in Lck SH3 upon binding to the LBD1 domain of Herpesvirus
      saimiri Tip.
AB  - The Tip protein from Herpesvirus saimiri interacts with the SH3 domain from the
      Src-family kinase Lck via a proline-containing sequence termed LBD1. Src-family
      kinase SH3 domains related to Lck have been shown to be dynamic in solution and
      partially unfold under physiological conditions. The rate of such partial
      unfolding is reduced by viral protein binding. To determine if the Lck SH3 domain
      displayed similar behavior, the domain was investigated with hydrogen exchange
      and mass spectrometry. Lck SH3 was found to be highly dynamic in solution. While
      other SH3 domains require as much as 10,000 sec to become totally deuterated, Lck
      SH3 became almost completely labeled within 200 sec. A partial unfolding event
      involving 8-10 residues was observed with a half-life of approximately 10 sec.
      Tip LBD1 binding did not cause gross structural changes in Lck SH3 but globally
      stabilized the domain and reduced the rate of partial unfolding by a factor of
      five. The region of partial unfolding in Lck SH3 was found to be similar to that
      identified for other SH3 domains that partially unfold. Although the sequence
      conservation between Lck SH3 and other closely related SH3 domains is high, the
      dynamics do not appear to be conserved.

PMID- 17008725
TI  - RbBa2(N3)5: a new ternary azide.
AB  - Rubidium dibarium pentaazide, RbBa2(N3)5, was prepared from an aqueous solution
      of the binary azides at room temperature. It crystallizes in the monoclinic
      system (space group P2/n). Two central atoms of azide groups occupy the 2c (1)
      and 2b (1) positions, another azide group lies completely on a twofold axis (2f),
      while Rb atoms are situated in 2e (2) positions. The crystal structure of
      RbBa2(N3)5 can be regarded as a distorted AlB2-type arrangement of the metal
      atoms, with the azide groups occupying the voids between the cations. This
      results in coordination numbers of 8 (Rb) and 10 (Ba). The N-N distances are in
      the range 1.169 (8)-1.190 (5) A, typical for the azide group.

PMID- 17008723
TI  - The MRG domain of human MRG15 uses a shallow hydrophobic pocket to interact with
      the N-terminal region of PAM14.
AB  - MRG15 is a transcription factor expressed in a variety of human tissues, and its
      orthologs have been found in many other eukaryotes which constitute the MRG
      protein family. It plays a vital role in embryonic development and cell
      proliferation, and is involved in cellular senescence. The C-terminal part of
      MRG15 forms a conserved MRG domain which is involved in interactions with the
      tumor suppressor protein retinoblastoma and a nucleoprotein PAM14 during
      transcriptional regulation. We report here the characterization of the
      interaction between the MRG domain of human MRG15 and PAM14 using both yeast two
      hybrid and in vitro binding assays based on the crystal structure of the MRG
      domain. The MRG domain is predominantly hydrophobic, and consists of mainly alpha
      helices that are arranged in a three-layer sandwich topology. The hydrophobic
      core is stabilized by interactions among a number of conserved hydrophobic
      residues. The molecular surface is largely hydrophobic, but contains a few
      hydrophilic patches. Structure-based site-directed mutagenesis studies identified
      key residues involved in the binding of PAM14. Structural and biochemical data
      together demonstrate that the PAM14 binding site is consisted of residues Ile160,
      Leu168, Val169, Trp172, Tyr235, Val268, and Arg269 of MRG15, which form a shallow
      hydrophobic pocket to interact with the N-terminal 50 residues of PAM14 through
      primarily hydrophobic interactions. These results provide the molecular basis for
      the interaction between the MRG domain and PAM14, and reveal insights into the
      potential biological function of MRG15 in transcription regulation and chromatin
      remodeling.

PMID- 17008724
TI  - Variants of DsRed fluorescent protein: Development of a copper sensor.
AB  - The fluorescence quenching of drFP583 (DsRed) protein by metal ions was
      investigated. CuSO4 reversibly and pH dependently quenched the red emission at
      583 nm of drFP583. The copper binding constant was 15 mM. Following random
      mutagenesis, blue- and red-shifted mutants of drFP583 were generated, and their
      metal sensing properties were examined. Mutant gRF possessed properties similar
      to green fluorescent protein and had a 18 mM copper binding constant. Mutant
      Rmu162 had an extraordinary red-shifted emission peak at 620 nm. A third mutant,
      Rmu13, had dual emission peaks at 500 nm and 583 nm and possessed the properties
      of a copper sensor with a binding constant of 11 mM.

PMID- 17008726
TI  - The new lead vanadylphosphate Pb2VO(PO4)2.
AB  - The structure of dilead vanadium oxide bis(phosphate) contains corrugated layers
      formed by VO5 square pyramids oriented in opposite directions in a chessboard
      fashion. The pyramids are connected by tetrahedral PO4 groups. The layers are
      separated by the Pb atoms and isolated PO4 tetrahedra.

PMID- 17008727
TI  - catena-Poly[bis[(1,10-phenanthroline)nickel(II)]-mu-3,6-dicarboxycyclohexane
      1,2,4,5-tetracarboxylato].
AB  - In the title compound, [Ni2(C12H8O12)(C12H8N2)2]n, the 3,6-dicarboxycyclohexane
      1,2,4,5-tetracarboxylate (H2chhc4-) anion has crystallographically imposed C(2)
      symmetry and bridges the six-coordinate Ni atoms to generate polymeric
      infinity1[Ni2(H2chhc)2/2(C12H8N2)2] chains extending in the [010] direction. The
      coordination polymer chains are linked into a three-dimensional framework by O
      H...O and C-H...O hydrogen bonds.

PMID- 17008728
TI  - A linear Fe-O-Fe unit in bis(dibenzyldimethylammonium) mu-oxo
      bis[tribromoferrate(III)].
AB  - The title compound, (C16H20N)2[Fe2Br6O], crystallizes with one
      dibenzyldimethylammonium cation and one half of a mu-oxo
      bis[tribromoferrate(III)] anion in the asymmetric unit. The bridging oxo group is
      situated on an inversion centre, resulting in a linear conformation for the Fe-O
      Fe unit. The iron(III) cations have tetrahedral geometry, with bond angles in the
      range 106.8 (1)-112.2 (1) degrees . The ion pairs are held together by Coulombic
      forces and C-H...Br hydrogen bonds. Each Br- anion forms one hydrogen bond. No C
      H...O hydrogen bonds are found between the O atom in the Fe-O-Fe unit and
      surrounding counter-cations, consistent with the linear configuration of the Fe-O
      Fe unit.

PMID- 17008729
TI  - Cis-bis[(3-aminopropyl)dimethylphosphine-kappa2N,P]palladium(II) dichloride
      methanol solvate.
AB  - In the title compound, cis-[Pd(C5H14NP)2]Cl2.CH4O, the coordination geometry
      around the PdII center is distorted square planar, with a cis-P2N2 configuration
      of the two chelating (3-aminopropyl)dimethylphosphine (pdmp) ligands. The six
      membered pdmp chelate rings adopt chair conformations, and pairing of the chairs
      designates the complex cation as a (Cs)-chair2 conformer. The distances between
      the PdII center and the Cl- anions are greater than 4.5 A, indicating no obvious
      interaction.

PMID- 17008730
TI  - Redetermination of the trigonal prismatic complex tris(cis-1,2-diphenylethylene
      1,2-dithiolato)rhenium.
AB  - The first trigonal prismatic molecular compound characterized by single-crystal X
      ray diffraction, [Re(C14H10S2)3], has been redetermined using modern laboratory
      equipment. The new experiment reaffirms the results of the original. Since then,
      numerous tris-dithiolene complexes have been structurally characterized, having
      geometries ranging from trigonal prismatic to nearly octahedral. An examination
      of the coordination geometries of these structures is included.

PMID- 17008731
TI  - Chloro(diethylenetriamine)copper(II) chloride: a disordered quasi-one-dimensional
      structure.
AB  - The title structure, [CuCl(C4H13N3)]Cl, consists of alternating [CuCl(dien)]+
      (dien is diethylenetriamine) and Cl- ions arranged in quasi-one-dimensional
      stacks along the crystallographic a axis and forming tetragonally elongated
      octahedral coordination shells around each Cu atom [equatorial Cu-Cl = 2.2552 (8)
      A, and axial Cu-Cl = 2.831 (1) and 3.341 (1) A]. Crystallographic mirror planes
      bisect each stack vertically through the Cu, Cl and central N atoms, and
      horizontally through the [CuCl(dien)]+ cation. The horizontal mirrors lead to
      each atom in the puckered [CuCl(dien)]+ cations being disordered over two
      crystallographically equivalent sites. Comparison of the title structure with its
      Br and I analogues shows a growing influence of hydrogen bonding relative to
      coordination bonds on traversing the series I < Br < Cl.

PMID- 17008732
TI  - Tetraaqua(7-hydroxy-5-oxidoflavone-6-sulfonato-kappa2O4,O5)nickel(II)
      dimethylformamide solvate monohydrate.
AB  - In the title compound, [Ni(C15H8O7S)(H2O)4].C3H7NO.H2O, the NiII cation is
      chelated by a 7-hydroxy-5-oxidoflavone-6-sulfonate ligand through one oxide and
      one carbonyl O atom, and the sixfold coordination is completed by four aqua
      ligands. Individual molecules are linked into hydrogen-bonded dimers by way of
      five pairs of O-H...O hydrogen bonds. These dimers, in turn, determine a three
      dimensional supramolecular arrangement through a variety of interdimeric
      interactions, such as O-H...O, C-H...O and pi-pi stacking.

PMID- 17008733
TI  - Comparison of copper imine and amine podates: geometric consequences of podand
      size and donor type.
AB  - The imine podands tris[(2-nitrobenzylidene)aminoethyl]amine and tris[(2
      nitrobenzylidene)aminopropyl]amine both stabilize copper(I), forming {tris[(2
      nitrobenzylidene)aminoethyl]amine-kappa4N}copper(I) perchlorate acetonitrile
      disolvate, [Cu(C27H27N7O6)]ClO4.2CH3CN, (II), and {tris[(2
      nitrobenzylidene)aminopropyl]amine-kappa4N}copper(I) perchlorate,
      [Cu(C30H33N7O6)]ClO4, (VI), respectively. The larger propyl-based ligand is a
      poorer fit for the CuI ion. The reduced amine podand tris[(2
      nitrobenzyl)aminoethyl]amine binds CuII and the resulting compound,
      chloro{tris[(2-nitrobenzyl)aminoethyl]amine-kappa4N}copper(II) chloride ethanol
      solvate, [Cu(C27H33N7O6)Cl]Cl.C2H5OH, (IV), shows both intra- and intermolecular
      hydrogen bonding, which gives rise to RRS or SSR conformations in the podand
      strands rather than the expected pseudo-threefold symmetry.

PMID- 17008734
TI  - Supramolecular assembly of (methanol)[10,15,20-tris(4-cyanophenyl)-5-(4
      pyridyl)porphyrinato]zinc(II) by intermolecular hydrogen bonding and weak
      coordination.
AB  - The crystal structure of the title compound, [Zn(C46H24N8)(CH4O)], consists of
      two-dimensional supramolecular arrays sustained by O-H...N(pyridyl) hydrogen
      bonding and weak Zn...NC coordination. The interlayer organization in the crystal
      structure is characterized by tight stacking of the corrugated layers.

PMID- 17008735
TI  - Solvent water tapes in two hydrates of mu-oxo-bis[bis(2,2'-bipyridine
      kappa2N,N')(sulfato-kappaO)iron(III)].
AB  - The title compound, [Fe2O(SO4)2(C10H8N2)4], crystallizes as two different
      hydrates, viz. 11H2O, (I), and 15H2O, (II). The complex is binuclear, in which
      the two FeIII atoms are coordinated in an octahedral geometry to four N atoms
      from the two bipyridine ligands, to one O atom from the sulfate ion and to an
      oxide ion on a twofold axis, which acts as a bridge between the symmetry-related
      units. The Fe...Fe separation is 3.556 (4) A and the Fe-O-Fe angle is 161.6 (2)
      degrees in (I); the corresponding values are 3.544 (1) A and 165.8 (2) degrees in
      (II). In (II), one of the O atoms of the sulfate ion is disordered over two
      positions. In both compounds, the solvent water molecules form slightly different
      one-dimensional hydrogen-bonded networks which pass along the c axis of the unit
      cell. In (I), three solvent water molecules and, in (II), one solvent water
      molecule, are situated on the twofold axis. In both (I) and (II), the central O
      atom of the metal complex lies on a twofold axis.

PMID- 17008736
TI  - Hydrogen bonding and pi-pi stacking in methylaminium 4',7-dihydroxyisoflavone-3'
      sulfonate dihydrate and hexaaquairon(II) bis(4',7-diethoxyisoflavone-3'
      sulfonate) tetrahydrate.
AB  - In methylaminium 4',7-dihydroxyisoflavone-3'-sulfonate dihydrate, CH6N+.C15H9O7S
      .2H2O, 11 hydrogen bonds exist between the methylaminium cations, the isoflavone
      3'-sulfonate anions and the solvent water molecules. In hexaaquairon(II) bis(4',7
      diethoxyisoflavone-3'-sulfonate) tetrahydrate, [Fe(H2O)6](C19H17O7S)2.4H2O, 12
      hydrogen bonds exist between the centrosymmetric [Fe(H2O)6]2+ cation, the
      isoflavone-3'-sulfonate anions and the solvent water molecules. Additional pi-pi
      stacking interactions generate three-dimensional supramolecular structures in
      both compounds.

PMID- 17008737
TI  - Diaquabis[2'-(4,5-diazafluoren-9-ylidene)picolinohydrazidato-kappa2N,O]zinc(II)
      tetrahydrate: a metal-water chain complex containing cyclic water hexamers.
AB  - In the title compound, [Zn(C17H10N5O)2(H2O)2].4H2O, cyclic water hexamers forming
      one-dimensional metal-water chains are observed. The water clusters are trapped
      by the co-operative association of coordination interactions and hydrogen bonds.
      The ZnII ion resides on a centre of symmetry and is in an octahedral coordination
      environment comprising two O atoms and two N atoms from two 2'-(4,5-diazafluoren
      9-ylidene)picolinohydrazidate ligands and two water molecules.

PMID- 17008738
TI  - A chloro-bridged dinuclear phosphinitopalladium complex, di-mu-chloro
      bis[(diphenoxyphosphinite-kappaP)(diphenoxyphosphinito-kappaP)palladium(II)].
AB  - The title compound, [Pd2(C12H10O3P)2Cl2(C12H11O3P)2], consists of a dinuclear mu
      chloro-bridged palladium unit with two diphenoxyphosphinite groups per Pd atom,
      linked together by a hydrogen bond. The asymmetric unit contains one half of the
      molecule, with the other half generated by an inversion centre. The geometry
      around the P atoms may be described as distorted tetrahedral. Adjacent molecules
      of the complex are linked by weak C-H...O and C-H...Cl hydrogen bonds. The
      structure is additionally stabilized by pi-pi stacking interactions between the
      aryl rings. These interactions form a herring-bone pattern in the crystal
      structure.

PMID- 17008739
TI  - Poly[[[mu-5,10,15,20-tetrakis(4-methoxycarbonylphenyl)porphyrinato(2-)]zinc(II)]
      N,N'-dimethylacetamide disolvate].
AB  - The crystal structure of the title compound, {[Zn(C52H36N4O8)].2C4H9NO}n,
      consists of two-dimensional coordination polymers of the six-coordinate zinc
      porphyrin unit [Zn-N = 2.039 (2) and 2.061 (2) A, and Zn-O = 2.540 (2) A], which
      intercalate between the molecules of N,N-dimethylacetamide solvent. The Zn atom
      lies on an inversion centre.

PMID- 17008740
TI  - Bis(ethylenediaminium) bis[oxalohydroxamato(3-)]nickelate(II) dihydrate.
AB  - The title compound, (C2H10N2)2[Ni(C2HN2O4)2].2H2O, has an ionic structure
      containing a centrosymmetric complex 4- anion, charge-balancing ethylenediaminium
      dications and solvent water molecules. The oxalohydroxamate unit is triply
      deprotonated and forms five-membered chelate rings with the central Ni ion; the
      Ni ion lies on an inversion centre. The two hydroxamate O atoms in the complex
      anion are linked by short intramolecular hydrogen bonds.

PMID- 17008741
TI  - Catena-poly[[diisothiocyanatocadmium(II)]-bis[mu-1,3-bis(1,2,4-triazol-1
      ylmethyl)benzene-kappa2N4:N4']]: a double-chain coordination polymer.
AB  - The coordination geometry of the CdII atom in the title complex,
      [Cd(NCS)2(C12H12N6)2]n or [Cd(NCS)2(mbtz)2]n, where mbtz is 1,3-bis(1,2,4-triazol
      1-ylmethyl)benzene, is a distorted compressed octahedron in which the CdII atom
      lies on an inversion centre, coordinated by four N atoms from the triazole rings
      of four mbtz ligands and two N atoms from two monodentate NCS- ligands. The
      structure is polymeric, with 24-membered spiro-fused rings extending along [100]
      and with the 24-membered ring containing two inversion-related mbtz molecules.

PMID- 17008742
TI  - Two-dimensional hydrogen-bond network in bis[(ferrocenylmethyl)dimethylammonium]
      sulfate pentahydrate.
AB  - In the title compound, [Fe(C5H5)(C8H13N)]2(SO4).5H2O, the Fe-C bond lengths lie
      in the range 2.021 (3)-2.047 (2) A. Intermolecular N-H...O and O-H...O hydrogen
      bonds link the cations, sulfate anions and water molecules into a two-dimensional
      hydrogen-bonded network, which stabilizes the crystal packing.

PMID- 17008743
TI  - 2,5-Dicarboxyanilinium chloride monohydrate.
AB  - The title compound, C8H8NO4+.Cl-.H2O, is the chlorohydrated form of 2
      aminobenzene-1,4-dicarboxylic acid, the basic crystal structure of which is still
      not known. Molecules are linked by classical N-H...O, O-H...O, N-H...Cl and O
      H...Cl hydrogen bonds, mainly along the molecular plane, into sheets built by
      unusual R6(4)(26), R6(4)(22) and R4(3)(22) rings. The stacking between layers is
      stabilized by another N-H...Cl hydrogen bond and by pi-pi interactions between
      aromatic rings facing each other.

PMID- 17008744
TI  - 2,6-Dibromo-3,5-dimethylpyridine and 2,6-diiodo-3,5-dimethylpyridine.
AB  - The title compounds 2,6-dibromo-3,5-dimethylpyridine, C7H7Br2N, (I), and 2,6
      diiodo-3,5-dimethylpyridine, C7H7I2N, (II), constitute the first structurally
      characterized examples of 2,6-dihalo-3,5-dimethylpyridines. Compound (I)
      crystallizes as a racemic twin with two symmetry-independent molecules in the
      asymmetric unit, while (II) is non-planar with the pyridine ring slightly
      deformed into a saddle shape, and exhibits crystallographically imposed twofold
      symmetry. Both (I) and (II) exhibit aromatic face-to-face pi-stacking in the
      solid state, although there are no other long-range interactions. In (I),
      alternate molecules are oriented at 90 degrees, resulting in X-shaped columns,
      while in (II), molecules pack in a parallel fashion, leading to a zigzag array.

PMID- 17008745
TI  - 2-Amino-7-chloro-2'-deoxytubercidin.
AB  - In 4-chloro-7-(2-deoxy-beta-D-erythro-pentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
      2,4-diamine, C11H14ClN5O3, the conformation of the N-glycosylic bond is between
      anti and high-anti [chi = -102.5 (6) degrees]. The 2'-deoxyribofuranosyl unit
      adopts the C3'-endo-C4'-exo (3T4) sugar pucker (N-type) with P = 19.6 degrees and
      taum = 32.9 degrees [terminology: Saenger (1989). Landolt-Bornstein New Series,
      Vol. 1, Nucleic Acids, Subvol. a, edited by O. Madelung, pp. 1-21. Berlin:
      Springer-Verlag]. The orientation of the exocyclic C4'-C5' bond is +ap (trans)
      with a torsion angle gamma = 171.5 (4) degrees. The compound forms a three
      dimensional network that is stabilized by four intermolecular hydrogen bonds (N
      H...O and O-H...N) and one intramolecular hydrogen bond (N-H...Cl).

PMID- 17008746
TI  - A hydrogen-bonded heterodimer of 1-(4-hexyloxyphenyl)pyridin-4(1H)-one with 4
      cyanobenzoic acid.
AB  - The two components of the title heterodimer, C17H21NO2.C8H5NO2, are linked end-to
      end via O-H...O(=C) and C-H...O(=C) hydrogen-bond interactions. Additional
      lateral C-H...O interactions link the dimers in a side-by-side fashion to produce
      wide infinite molecular ribbons. Adjacent ribbons are interconnected via pi-pi
      stacking and C-H...pi(arene) interactions. This structure represents the first
      evidence of robust hydrogen-bond formation between the moieties of pyridin-4(1H)
      one and benzoic acid.

PMID- 17008747
TI  - A unique tautomer of 1-n-hexyl-3-phenyl-1H-pyrazol-5-ol.
AB  - In the title compound, C15H20N2O, the bond distances and angles are consistent
      with the presence of the hydroxy tautomer. This tautomer was unambiguously
      determined by the clear presence of a H atom bonded to oxygen, as well as the
      total absence of any residual electron density around the N atom in the
      heterocycle, thus precluding any possibility of desmotropism.

PMID- 17008748
TI  - Dihydrobis(methylamine)borate triiodide.
AB  - Both cation and anion in the title compound, C2H12BN2+.I3-, lie on a
      crystallographic mirror plane and are bound in the lattice by N-H...I- hydrogen
      bonds, forming layers. Methyl-H-borane-H dihydride [-C-H(delta+)...(delta-)H-B-]
      interactions between molecules crosslink adjacent layers, giving ;sandwich'
      stacking along the a axis.

PMID- 17008749
TI  - Hydrogen-bonding and pi-pi interactions in 2-amino-4,6-dimethylpyrimidinium
      salicylate.
AB  - In the crystal structure of the title compound, C6H10N3+.C7H5O3-, the asymmetric
      unit contains four crystallographically independent 2-amino-4,6
      dimethylpyrimidinium and salicylate ions (Z = 8). In each of these, one of the
      pyrimidine N atoms is protonated, and the carboxylate group of the salicylate ion
      interacts with the pyrimidine group through a pair of N-H...O hydrogen bonds,
      forming an R2(2)(8) motif. The pyrimidine cations also form base pairs via a pair
      of N-H...N hydrogen bonds (involving the amino group and the unprotonated ring N
      atom), forming another R2(2)(8) motif. Three such R2(2)(8) motifs, fused
      together, constitute a closed cyclic aggregate, and the linking of these
      aggregates, arranged in consecutive layers, can be analysed in terms of off-face
      stacking interactions.

PMID- 17008750
TI  - 3-[5-(4-Bromophenyl)-1H-pyrazol-3-ylamino]-5,5-dimethylcyclohex-2-en-1-one-(Z)-3
      (4-bromophenyl)-3-chloroacrylonitrile (2/1): a stoichiometric cocrystal of a
      reaction product with one of its early precursors.
AB  - The title compound, 2C17H18BrN3O.C9H5BrClN, was crystallized from the reaction
      between 5,5-dimethylcyclohexane-1,3-dione, triethyl orthoformate and 5-amino-3-(4
      bromophenyl)pyrazole, which had itself been prepared from the reaction between
      (Z)-3-(4-bromophenyl)-3-chloroacrylonitrile and hydrazine. The compound is a
      stoichiometric 2:1 cocrystal of the reaction product 3-[5-(4-bromophenyl)-1H
      pyrazol-3-ylamino]-5,5-dimethylcyclohex-2-en-1-one and the early reactant (Z)-3
      (4-bromophenyl)-3-chloroacrylonitrile. The two independent molecules of cyclohex
      2-en-1-one are linked by N-H...N and N-H...O hydrogen bonds into complex bilayers
      and the molecules of acrylonitrile are trapped within large cavities in the
      substructure formed by the cyclohex-2-en-1-one molecules.

PMID- 17008751
TI  - Hydrogen-bonding motifs in 4-carboxyphenylammonium nitrate and perchlorate
      monohydrate, and in bis(4-carboxyphenylammonium) sulfate.
AB  - In the title compounds, C7H8NO2+.NO3-, (I), C7H8NO2+.ClO4-.H2O, (II), and
      2C7H8NO2+.SO4(2-), (III), the carboxyl planes of the 4-carboxyphenylammonium
      cations are twisted from the aromatic plane. A homonuclear C(8) hydrogen-bonding
      motif of 4-carboxyphenylammonium cations is observed in both (I) and (II),
      leading to ;head-to-tail' layers. The cations in (III) form carboxyl group
      dimers, making a graph-set motif of R2(2)(8). In all the structures, anions
      connect the cationic layers and an infinite chain running along the c axis is
      observed, having the C2(2)(6) graph-set motif. Interestingly, in (II), the anions
      are connected through weak hydrogen bonds involving the water molecules, leading
      to a graph-set motif of R4(4)(12). Alternate hydrophobic and hydrophilic layers
      are observed in all three compounds as a result of the column-like arrangement of
      the aromatic rings of the cations and the anions. Furthermore, in (I), head-to
      tail N-H...O interactions and interactions linking the cations and anions form an
      R6(4)(16) hydrogen-bonding motif, resulting in a pseudo-inversion centre at (1/2,
      1/2, 0).

PMID- 17008752
TI  - Four substituted benzohydrazides: hydrogen-bonded structures in one, two and
      three dimensions.
AB  - The molecules of 2,6-dichlorobenzohydrazide, C7H6Cl2N2O, are linked into simple
      chains by a single N-H...O hydrogen bond, while in the isomeric compound 2,4
      dichlorobenzohydrazide, the molecules are linked by N-H...N and N-H...O hydrogen
      bonds into complex sheets comprising an inner polar layer sandwiched between two
      non-polar layers. In 4-amino-2-chlorobenzohydrazide monohydrate, C7H8ClN3O.H2O,
      the components are linked into a three-dimensional framework by a combination of
      O-H...O, O-H...N, N-H...N and N-H...O hydrogen bonds, and in 2
      nitrobenzohydrazide, C7H7N3O3, a three-dimensional framework is formed by a
      combination of N-H...N and N-H...O hydrogen bonds.

PMID- 17008753
TI  - Chalcone epoxide intermediates in the syntheses of lignin-related
      phenylcoumarans.
AB  - Compounds (2R*,3S*)-1-(3,4-dimethoxyphenyl)-3-{3-methoxy-2-[(2R*)-tetrahydropyran
      2-yloxy]phenyl}-2,3-epoxy-1-propanone, C23H26O7, (I), and trans-1-(3,4
      dimethoxyphenyl)-3-[3-methoxy-2-(methoxymethoxy)phenyl]-2,3-epoxy-1-propanone,
      C20H22O7, (II), were obtained on epoxidation of chalcones. The stereochemistries
      of (I) and (II) were elucidated. In both compounds, the substituents on the
      oxirane ring are trans-oriented. Compound (I) was obtained together with a
      diastereometric form that differs from (I) with respect to the configuration of
      the asymmetric C atom in the tetrahydropyran group. The geometries of the
      substituted oxirane rings of (I) and (II) are very similar. The hydrogen-bonding
      patterns, mediated via weak C-H...O interactions, differ considerably. The
      crystal structures of (I) and (II) are compared with those of related chalcone
      epoxides. The conversion of (I) and (II) into lignin-related phenylcoumarans is
      discussed.

PMID- 17008754
TI  - Cyclodecyl 4-nitrophenylacetate.
AB  - Cyclodecyl 4-nitrophenylacetate, C18H25NO4, has its ten-membered ring in the
      expected diamond-lattice boat-chair-boat [2323] conformation, with the
      substituent 4-nitrophenylacetoxy group in the BCB IIIe position. The ester unit
      has the expected Z conformation, with an O=C-O-C torsion angle of -0.3 (3)
      degrees, and the connection to the benzene ring is nearly perpendicular to the
      ester, with an O=C-C-C torsion angle of 85.5 (2) degrees. An intermolecular
      contact exists between the ester C atom and a nitro O atom, having a C...O
      distance of 2.909 (2) A.

PMID- 17008755
TI  - (2S,RS)-6-Phenyl-1-(p-tolylsulfinyl)hexa-3(E),5(E)-dien-2-ol.
AB  - The molecule of the title compound, C19H20O2S, corresponds to a chiral
      sulfinyldienol with two stereogenic centres, viz. the C atom susbtituted by the
      hydroxy group and the sulfinyl S atom. The molecule displays a V-shape in the
      solid state. The dihedral angle defined by the least-squares planes of the
      aromatic rings is 72.9 (1) degrees. The packing pattern exhibits the following
      intermolecular hydrogen bonds: one O-H...O [H...O = 1.98 A, O...O = 2.785 (4) A
      and O-H...O = 166 degrees] and two C-H...O [H...O = 2.58 and 2.60 A, C...O =
      3.527 (5) and 3.347 (5) A, and C-H...O = 164 and 134 degrees]. These define a
      chain along b.

PMID- 17008756
TI  - Comparison of the growth performances of offspring produced by a pair of cloned
      cattle and their nuclear donor animals.
AB  - In the present study, the growth performance of a calf produced by mating a
      somatic cell cloned dam and sire was compared with that of its full siblings
      produced by mating the cattle used as nuclear donors for the cloned animals. The
      somatic cell cloned dam and sire were derived from cultured cumulus cells and ear
      cells, respectively. The cloned dam was artificially inseminated with semen from
      the cloned sire. A female calf was produced that was reared under general group
      feeding conditions. The calf was subjected to a clinical examination and to
      hematology, serum biochemistry, and telomere length analyses; all of these tests
      indicated that the calf was normal. The growth characteristics (body weight and
      shoulder height) of the calf fell within the range of the full siblings of the
      same sex produced by mating the animals used as the nuclear donors of clones.
      These findings suggest that the same breeding performance is expected from mating
      a cloned dam and sire as from mating the animals used as nuclear donors for the
      clones.

PMID- 17008758
TI  - Seasonal differences in the parameters of luteinizing hormone release to
      exogenous gonadotropin releasing hormone in prepubertal Holstein heifers in
      Sapporo.
AB  - Stress due to summer heat has adverse effects on reproduction in Holstein dairy
      cattle. Summer suppression of reproduction of Holsteins can pose an important
      economic problem, even in Hokkaido prefecture located in the northern region of
      Japan. Hokkaido is one of the most important dairy farming areas of Japan. This
      study is an attempt to clarify the seasonal differences in the parameters of
      luteinizing hormone (LH) response to exogenous gonadotropin releasing hormone
      (GnRH) in Sapporo, Hokkaido, Japan. A total of 12 prepubertal heifers received an
      injection with GnRH analogue intramuscularly in either May (n=4, May group), July
      (n=4, July group), or November (n=4, November group), and serial blood samples
      were collected to analyze the parameters of the LH response curve after GnRH
      injection. The parameters were as follows: the basal LH concentration, peak LH
      concentration, duration from the time of GnRH injection to the time of the peak
      LH concentration, and area under the LH response curve (AUC). There were no
      significant differences in the basal and peak LH concentrations or the AUC among
      the three groups. The July group reached the LH peak significantly (P<0.05)
      faster than the May group, but there was no significant difference with the
      November group. Therefore, the results of the present study do not demonstrate an
      effect of summer heat on the LH response to the exogenous GnRH in Holstein
      heifers.

PMID- 17008757
TI  - Acute lipoprivation suppresses pulsatile luteinizing hormone secretion without
      affecting food intake in female rats.
AB  - The present study examined the effect of acute lipoprivation on pulsatile
      luteinizing hormone (LH) secretion in both normal-fat diet, ad libitum-fed and
      fasted female rats. To produce an acute lipoprivic condition, mercaptoacetate
      (MA), an inhibitor of fatty acid oxidation, was administered intraperitoneally to
      ad libitum-fed or 24-h fasted ovariectomized (OVX) rats with or without an
      estradiol (E2) implant, that produces a negative feedback effect on LH pulses.
      The steroid treatment was performed to determine the effect of estrogen on
      lipoprivic changes in LH release, because estrogen enhances fasting- or
      glucoprivation-induced suppression of LH pulses. Pulsatile LH secretion was
      suppressed by MA administration in a dose-dependent manner in the ad libitum-fed
      OVX and OVX+E2 rats. LH pulses were more severely suppressed in the 24-h-fasted
      OVX and OVX+E2 rats compared to the ad libitum-fed rats. Estrogen slightly
      enhanced lipoprivic suppression but the effect was not significant. In the
      present study, increased plasma glucose and free-fatty acid concentrations may
      indicate a blockade of fatty acid metabolism by the MA treatment, but food intake
      was not affected by any of the MA doses. Acute vagotomy did not block lipoprivic
      suppression of LH pulses. Thus, the present study indicates that lipid metabolism
      is important for maintenance of normal reproductive function even in rats fed a
      normal-fat diet and lipoprivation may be more critical in fasted animals that
      probably rely more heavily on fatty acid oxidation to maintain appropriate
      metabolic fuel levels. In addition, failure of blockade of lipoprivic LH
      inhibition by vagotomy suggests that lipoprivic information resulting in LH
      suppression is not transmitted to the brain via the vagus nerve.

PMID- 17008759
TI  - Myogenic and adipogenic properties of goat skeletal muscle stem cells.
AB  - The aims of the present study were to establish a culture system for goat
      skeletal muscle stem cells and to examine their myogenic and adipogenic
      properties in vitro. Cells were isolated from the skeletal muscle of the Shiba
      goat and cultured in vitro. Most of the cells were positive for myogenic markers,
      such as Pax7, MyoD, and desmin, and immunocytochemistry revealed they
      differentiated to form myotubes expressing myosin heavy chain, indicating they
      were highly myogenic. Myogenic differentiation was strongly suppressed by the
      addition of basic fibroblast growth factor, while proliferation was unaffected.
      When the cells were cultured in adipogenic differentiation medium, some of the
      cells differentiated into mature adipocytes that stained with Oil Red-O. These
      cells were immunocytochemically positive for adipogenic markers, including
      peroxisome proliferator-activated receptor-gamma (PPAR gamma) and CCAAT/enhancer
      binding protein-alpha (C/EBP alpha). These results clearly demonstrate the
      presence of both myogenic and adipogenic stem cells in goat skeletal muscle.

PMID- 17008760
TI  - Fecal progestagen and estrone during pregnancy in a giraffe: a case report.
AB  - The present study was carried out to measure fecal progestagen and estrone
      concentrations during pregnancy in a giraffe and examine the possibility of
      utilizing this assay system for pregnancy diagnosis. Fecal samples were collected
      from a giraffe during her third and fourth parities and mixed with methanol to
      prepare a fecal solution. Diluted fecal solution was used for direct enzyme
      immunoassay for progestagen and estrone. The newborn calf from the third parity
      was viable, although that from the fourth parity died 5 days after calving. In
      the third parity, the giraffe's progestagen and estrone concentrations increased
      transiently from days 30 to 120 of pregnancy. Then, they decreased and remained
      low until day 330. This was followed by a drastic rise in both concentrations as
      parturition approached. Parturition caused a reduction in the progestagen and
      estrone concentrations of the feces. In the fourth parity, the progestagen
      concentration increased gradually after mating until day 320. This was followed
      by a reduction in the concentration until parturition. However, the estrone
      concentration fluctuated, and the duration and extent of the prepartum rise in
      concentration were shorter and lower than those of the third parity. The hormone
      dynamics of the third parity suggest the possibility of early pregnancy diagnosis
      by measuring progestagen or estrone between days 30 and 120 after mating.

PMID- 17008761
TI  - MR imaging of mouse lung using hyperpolarized 3He: image acquisition and T1
      estimation under spontaneous respiration.
AB  - PURPOSE: The purpose of this study was to acquire a hyperpolarized (HP) (3)He
      image of the mouse lung and to estimate 3He T1 in the lung from wash-out curve
      analysis under spontaneous respiration. MATERIALS AND METHODS: We first tested
      the K-Rb hybrid method for the spin-exchange optical pumping (SEOP) of 3He using
      a home-built noble gas polarizer operated at atmospheric pressure and then
      applied it to MR imaging and spectroscopy of the mouse lung. The longitudinal
      relaxation time (T1) of 3He in the mouse lung was estimated under spontaneous
      respiration by exploiting a novel method in which SF6 gas at thermal equilibrium
      was utilized in combination with the HP 3He gas in the quantitative wash-out
      curve analysis. This method utilizes the difference in the profile of the wash
      out curve of HP 3He and SF6 at thermal equilibrium. That is, the slope of the 3He
      wash-out curve in the semi-logarithmic plots is affected by 3 factors, including
      RF pulse angle, respiration, and T1, whereas the slope of the SF6 wash-out curve
      is only the function of respiratory term. RESULTS: A 3He lung image was obtained
      successfully, and we were able to estimate successfully 3He T1 in the mouse lung
      under spontaneous respiration using a novel method; the estimated T1 value was
      68+/-25 s, which was reasonable compared with the value calculated from the
      literature data measured during breath-hold. CONCLUSION: We succeeded in
      acquiring the first 3He image of mouse lung in vivo in this country, and our
      proposed method of estimating 3He T1 in the lung under spontaneous respiration is
      noninvasive and readily applied to animals and would be useful to evaluate the
      alveolar gas exchange function as well as oxygen partial pressure (pO2) in lungs
      of animals.

PMID- 17008762
TI  - Hemodynamic changes with liver fibrosis measured by dynamic contrast-enhanced MRI
      in the rat.
AB  - PURPOSE: To evaluate the hemodynamic changes of liver cirrhosis in the rat and
      investigate the relationship between hemodynamic changes and properties of
      fibrotic change in the liver. MATERIALS AND METHODS: Three rats with cirrhosis
      induced by thioacetamide (TAA), three with disease induced by carbon
      tetrachloride (CCl4), and three with no treatment were measured on dynamic MRI
      using a 1.5T scanner. Compartment and moment analysis were used to quantitate
      hemodynamic changes. RESULTS: Compartment model analysis showed that increased
      transition speed from vessels to the liver correlated with grade of liver
      fibrosis. Moment analysis demonstrated that decrease of area under the curve
      (AUC), mean residence time (MRT), variance of residence time (VRT), half life
      (T1/2) and increased total clearance (CL) correlated with grade of liver
      fibrosis. CONCLUSIONS: Hemodynamic changes in injured fibrotic liver may be
      influenced by the grade of fibrosis. Compartment model and moment analysis may be
      useful for evaluating hemodynamic changes in injured liver.

PMID- 17008763
TI  - Assessment of fixed charge density in regenerated cartilage by Gd-DTPA-enhanced
      MRI.
AB  - PURPOSE: Applying regenerated cartilage in a clinical setting requires
      noninvasive evaluation to detect the maturity of cartilage tissue. Magnetic
      resonance (MR) imaging of articular cartilage is well accepted and has been
      applied clinically in recent years. We attempt to establish a noninvasive method
      to evaluate the maturity of regenerated cartilage tissue using gadolinium
      enhanced MR imaging. METHODS: To reconstruct cartilaginous tissue, we embedded
      articular chondrocytes harvested from bovine humeral head in agarose gel and
      cultured the cells in vitro up to 4 weeks. The fixed charge density (FCD) of the
      cartilage was determined using MRI gadolinium exclusion method. The sulfated
      glycosaminoglycan (sGAG) content was determined by dimethylmethylene blue dye
      binding assay. RESULTS: The sGAG content and FCD of the regenerated cartilage
      increased with duration of culture. In the T1Gd maps, the [Gd-DTPA(2-)] in the
      specimen decreased, and the boundary between the sample disk and the bath
      solution of phosphate buffered saline (PBS) became clearer as time in culture
      increased. In the linear regression analysis, FCD and sGAG content correlated
      significantly. CONCLUSION: Gadolinium-enhanced MR imaging measurements can be
      useful predictors of the degree of cartilaginous tissue formation.

PMID- 17008764
TI  - Evaluation of RF heating on humerus implant in phantoms during 1.5T MR imaging
      and comparisons with electromagnetic simulation.
AB  - PURPOSE: To evaluate the effect of radiofrequency (RF) heating on a metallic
      implant during magnetic resonance imaging (MRI), temperatures at several
      positions of an implant were measured, and results are compared with
      electromagnetic simulations using a finite element method. METHODS: A humerus
      nail implant made of stainless steel was embedded at various depths of tissue
      equivalent gel-phantoms with loop (loop phantom) and partially cut loop (loop-cut
      phantom), and the phantoms were placed parallel to the static magnetic field of a
      1.5T MRI device. Scans were conducted at maximum RF for 15 min, and temperatures
      were recorded with 2 RF-transparent fiberoptic sensors. Finally, electromagnetic
      field analysis was performed. RESULTS: Temperatures increased at both ends of the
      implants at various depths, and temperature increase was suppressed with
      increasing depth. The maximum temperature rise was 12.3 degrees C at the tip of
      the implant and decreased for the loop-cut phantom. These tendencies resembled
      the results of electromagnetic simulations. CONCLUSION: RF heating was verified
      even in a nonmagnetizing metal implant in a case of excessive RF irradiation.
      Particularly, rapid temperature rise was observed at both ends of the implant
      having large curvatures. The difference in temperature increase by depth was
      found to reflect the skin-depth effect of RF intensity. Electromagnetic
      simulation was extremely useful for visualizing the eddy currents within the loop
      and loop-cut phantoms and for evaluating RF heating of a metallic implant for MRI
      safety.

PMID- 17008765
TI  - Evaluation of superparamagnetic iron oxide for MR imaging of liver injury: proton
      relaxation mechanisms and optimal MR imaging parameters.
AB  - PURPOSE: To investigate the proton relaxation mechanisms and the optimal MR
      imaging parameters in superparamagnetic iron oxide (SPIO)-enhanced MR imaging of
      liver injury. METHODS: A liver injury model was created in the rat using carbon
      tetrachloride. The T1 and T2 relaxation effects of SPIO in normal and injured
      liver were estimated by ex vivo relaxometry. In vivo laser confocal microscopy of
      the liver was performed to simulate the distribution and clustering of SPIO
      particles in the hepatic macrophages. SPIO-enhanced MR imaging (1.5T) of normal
      and diseased rats was performed with variable parameters. The liver specimens
      were prepared for histopathological examination. RESULTS: Histopathological and
      laser confocal microscopic findings showed diffuse macrophage distribution but
      decreased intracellular clustering of SPIO in injured liver. Ex vivo relaxometry
      showed sustained T1 and T2 relaxation effects of SPIO in liver injury. On MR
      images obtained with moderate echo time (spin echo [SE] 2000/40 and gradient echo
      [GRE] 130/9.0/60 degrees), injured liver showed significantly lower decrease in
      signal-to-noise ratio (SNR) than the normal liver, whereas little difference in
      SNR was found between the normal and injured liver on heavily T2-(SE 2000/80) and
      T1-weighted (SE 300/11 and GRE 130/2.0/90 degrees) MR images. CONCLUSION: Pulse
      sequences with a moderately long echo time (TE) may be more appropriate than
      heavily T1- or T2-weighted images for distinguishing normal and injured liver in
      SPIO-enhanced MR imaging because of the maintained T1 and T2 relaxation effect
      but decreased T2* relaxation effect of SPIO in injured liver.

PMID- 17008766
TI  - White matter changes in elderly people: MR-pathologic correlations.
AB  - Magnetic resonance (MR) imaging features of white matter lesions, often seen in
      the elderly, are correlated with histologic findings. Dilatation of perivascular
      spaces is seen, especially in the frontal and/or parietal subcortical white
      matter; the spaces are less than 3 mm in diameter and have sharp margins with no
      perifocal abnormality. Old lacunar infarcts are larger than 3 mm in diameter and
      are irregularly shaped and accompanied by perifocal myelin pallor and gliosis.
      Periventricular hyperintensity, including cap and rim, histologically shows
      myelin pallor, dilatation of perivascular spaces, discontinuity of the ependymal
      lining, and subependymal gliosis. Deep and subcortical white matter
      hyperintensity reflects myelin pallor and dilatation of perivascular spaces.
      Diffuse white matter lesion, seen in Binswanger's disease, shows myelin pallor
      and tissue rarefaction associated with loss of myelin and axons. U-fibers are
      usually well preserved. Severe arteriosclerosis and arteriolosclerosis are
      usually seen in the white matter. Knowledge of the pathologic features of
      incidental changes in white matter helps in understanding MR imaging findings.

PMID- 17008767
TI  - Multi-volume fusion imaging of MR ductography and MR mammography for patients
      with nipple discharge.
AB  - Because nipple discharge is caused by carcinoma as well as benign disease,
      identification of intraductal abnormalities with ductography is important.
      Ductography is an invasive mammographic examination in which contrast material is
      injected directly into the duct. Failure to cannulate or extravasation may occur.
      Ductography shows evidence of lesions, such as filling defects, duct obstruction,
      or wall irregularity, but it does not reveal the lesion itself. Furthermore,
      ductography produces a two-dimensional image, so it does not show the shape of
      the dilated duct or the precise location of the intraductal lesion in the breast.
      We applied three-dimensional (3D) heavily T2-weighted imaging with fat
      suppression of the breast to produce MR ductography. The dilated ducts are seen
      in 3D as tubular structures with high signal, and intraductal abnormalities are
      seen as signal defects. Furthermore, MR ductography can show an obstructed duct
      that cannot be seen on ductography. We also performed 3D breast MRI with the
      intravenous infusion of contrast material to show the lesion itself. Finally, we
      fused these 2 volume images into a single 3D fused image that not only shows the
      existence of intraductal abnormality, but reveals the shape, size, and extent of
      lesion, allowing us to understand easily the relationship between the ducts with
      dilation and any intraductal lesions in the breast. We herein introduce and
      describe this noninvasive method and discuss various factors related to its
      diagnostic use.

PMID- 17008768
TI  - Giant angioleiomyoma in extremity: report of two cases.
AB  - Angioleiomyomas are smooth muscle tumors that occur most often in the extremities
      and are usually less than 2 cm in diameter. We present 2 case reports of giant
      angioleiomyoma. Case 1 was a 51-year-old woman with a 5-year history of a slowly
      growing mass 12x10 cm in diameter in the right posterior thigh. The tumor was
      larger than any previously reported. Case 2 was a 72-year-old man with an 8-year
      history of a slowly growing mass 6x6 cm in diameter in the left palm. The tumor
      was unique in that it grew to a giant size in the hand of the elderly patient.
      Magnetic resonance imaging of both cases confirmed the tumors' presence in the
      subcutis. T1-weighted images showed homogenous signal isointense to muscle. On T2
      weighted images, areas of hyperintensity and hypointensity intermingled. Three
      dimensional gadolinium-enhanced magnetic resonance angiography showed rapid
      initial enhancement followed by a gradual increase in enhancement, suggesting
      that the tumors were rich in vessels. Microscopic examination revealed numerous
      vascular channels embedded within a huge smooth muscle component.

PMID- 17008769
TI  - Combination therapy with the single inhaler salmeterol/fluticasone propionate
      versus increased doses of inhaled corticosteroids in patients with asthma.
AB  - BACKGROUND: Although results from a few meta-analyses were most uniformly
      supportive of the beneficial effect of combination therapy on lung function,
      there were inconsistent results on other endpoints such as asthma exacerbation.
      Single inhalers of salmeterol and fluticasone propionate have been available, and
      some studies compared the effect of combination products with increased doses of
      inhaled corticosteroids (ICSs) on several outcome variables. OBJECTIVES: We
      reviewed the studies systematically, providing a quantitative summary estimate on
      the efficacy and safety measures of the combination products. METHODS: We
      searched databases (Medline and Embase) from January 1997 to December 2005 using
      'fluticasone and salmerterol' or 'Seretide' or 'Advair', in combination with
      'randomized controlled trial'. The databases of GlaxoSmithKline Clinical Trial
      Register and Cochrane Controlled Trials Register, or relevant articles were
      searched for additional studies. RESULTS: Combination products had a
      comparatively low, but significant improvement in pulmonary function, with
      morning peak expiratory flow (PEF), evening PEF and FEV1 increasing by 17.86
      liters/min, 15.57 liters/min and 0.09 liter, respectively, compared with
      increased doses of inhaled corticosteroid (ICSs) over 12 weeks' treatment. But
      there were no statistically significant differences in other endpoints such as
      asthma exacerbation, overall withdrawal and drug-related adverse events, with the
      exception of overall adverse events and symptom free 24 h, which favored
      combination products. CONCLUSIONS: Thecombination products provided a
      statistically significant improvement in lung function and in symptoms but
      provided no significantly increased protection against exacerbation. Unless high
      doses of ICSs are required, there is insufficient evidence at present to
      recommend the use of combination products rather than increased moderate doses of
      ICSs as a first-line treatment for patients uncontrolled on their current doses
      of ICSs.

PMID- 17008770
TI  - A simple method for rapid separation of endothelial and smooth muscle mRNA
      reveals Na/K+ -ATPase alpha-subunit distribution in rat arteries.
AB  - BACKGROUND/AIMS: The endothelium has been recognized as a key component in the
      regulation of blood vessels. We designed a simple procedure to separate
      endothelial and smooth muscle RNA from rat aorta and mesenteric artery and used
      this method to establish the distribution of Na(+)/K(+)-ATPase alpha-subunit
      isoforms (NaKalpha1, NaKalpha2 and NaKalpha3) within the arterial wall. METHODS:
      Rat aorta was perfused with Tripure, a reagent for RNA isolation, yielding 3
      successive RNA fractions (E1-E3) and the remaining tissular RNA (Ao[E-]). A
      similar procedure was applied to the mesenteric artery. Gene expression was
      studied by semiquantitative reverse-transcription polymerase chain reaction.
      RESULTS: Compared to unperfused aorta (Ao[E+]), typical endothelial mRNAs were
      enriched 3- to 5-fold in E1-E3 but almost absent in Ao[E-], whereas smooth muscle
      mRNAs were low in E1-E3 but similarly expressed in Ao[E-] and Ao[E+]. NaKalpha1
      was uniformly expressed in all fractions, NaKalpha2 closely followed the
      expression pattern of smooth muscle markers and NaKalpha3 expression was weak and
      attributable to blood contamination. Comparable results were obtained with the
      mesenteric artery. CONCLUSION: We conclude that, in aorta and mesenteric artery,
      Tripure perfusion allows for a rapid and reliable separation of endothelial mRNA
      from smooth muscle mRNA, and that endothelium only expresses NaKalpha1, whereas
      smooth muscle expresses NaKalpha1 and NaKalpha2, but not NaKalpha3.

PMID- 17008771
TI  - Inhibition of hypoxia-inducible factor-1alpha and endothelial progenitor cell
      differentiation by adenoviral transfer of small interfering RNA in vitro.
AB  - RNA interference is applied to study gene function in different organisms and in
      various cell types. Little is known about the effect of RNA interference on human
      endothelial progenitor cells (EPCs) in vitro. To address this issue, short
      hairpin RNA targeting the human hypoxia inducible factor-1alpha (HIF-1alpha) was
      transferred into human EPCs by an adenoviral vector. HIF-1alpha mRNA and protein
      expression was dramatically and specifically downregulated after adeno-small
      interfering RNA (siRNA)-HIF-1alpha infection in cells under hypoxia, a condition
      in which HIF-1alpha would have been induced. This effect persisted for at least
      72 h and was accompanied by suppression of vascular endothelial growth factor
      (VEGF) mRNA and protein expression. The expression of endothelial cell markers
      CD31, VEGF receptor 2 (Flk-1) and eNOS as well as NO production were also
      markedly decreased. Functional studies showed HIF-1alpha knockdown via adenoviral
      siRNA transfer inhibited EPC colony formation, differentiation, proliferation and
      migration. These data indicate that specific gene knockdown via adenoviral
      transfer of siRNA is feasible in EPCs, and the effect is long-lasting. Our
      findings raise the possibility that such long-term modified human EPCs may be
      used to treat hypoxic tumor metastases that are known to be resistant to
      conventional therapeutic regimes.

PMID- 17008772
TI  - Pharmacology and statistics: recommendations to strengthen a productive
      partnership.
AB  - Critical to the discovery, development and rational use of drugs and vaccines are
      the foundational principles and proper application of statistics. However, in too
      many cases, there has been misuse of statistics and/or overemphasis on
      statistical significance (p < 0.05), as though this criterion possessed truth
      guaranteeing properties. To clarify confusion about the proper use of statistics
      in pharmacology, we summarize briefly the foundational principles of probability;
      the role of statistics in assessment of causality; the three basic uses of
      statistical methods, especially those employed in hypothesis testing; and current
      statistical issues in pharmacological research. We then review and provide
      examples of the meaning of statistical significance, the consequences of lack of
      randomization in epidemiology/observation studies, the criteria for measurement
      instrument validation, the problems with subgroup analyses, the need for multiple
      comparison statistical methods, and how to handle dropouts and missing data.
      Finally, based on sound experimental and statistical principles, we make a series
      of recommendations to both experimentalists and journal editors to improve
      published pharmacological experiments. These include widespread use of blinding
      and randomization and/or random selection of subjects in both basic and clinical
      pharmacology, mandatory use of rigorous evidentiary criteria in
      epidemiology/observation studies claiming causal associations, proper
      interpretation of statistical versus clinical/pharmacological significance,
      appropriate interpretation of meta-analyses, meaningful validation of methods,
      and a more rational statistical approach to subgroup analyses and genetic
      association studies.

PMID- 17008773
TI  - Extracellular signal-regulated kinase (ERK1/2) contributes to endotoxin-induced
      hyporeactivity via nitric oxide and prostacyclin production in rat aorta.
AB  - This study was conducted to determine if mitogen-activated protein kinases
      (MAPKs) such as extracellular signal-regulated kinase (ERK1/2) contribute to
      endotoxin-induced vascular hyporeactivity via nitric oxide (NO) and/or
      prostacyclin (PGI(2)) production in the rat isolated thoracic aorta. Incubation
      of endothelium-intact rings with endotoxin (100 microg/ml) for 4 h decreased the
      E(max) value and increased the EC(50) value of norepinephrine. The endotoxin
      induced increase in the EC(50) value of norepinephrine was decreased by phenylene
      1,3-bis[ethane-2-isothiourea] dihydrobromide (1,3-PBIT), a selective inducible NO
      synthase inhibitor, and U0126, a selective inhibitor of ERK1/2 phosphorylation by
      MAPK kinase. The endotoxin-induced decrease in the E(max) value of norepinephrine
      was reversed by 1,3-PBIT and further decreased by U0126. 1,3-PBIT and U0126
      decreased the endotoxin-induced increase in the tissue nitrite and 6-keto
      PGF(1)(alpha) levels. These data suggest that events related to the activation of
      ERK1/2 contribute to the endotoxin-induced hyporeactivity by increasing NO and
      PGI(2) production.

PMID- 17008774
TI  - Measuring the refractoriness of the electrically stimulated auditory nerve.
AB  - Intracochlear recordings in cochlear implant recipients provide access to the
      electrically evoked compound action potential (ECAP). ECAP thresholds are
      potential predictors of speech processor map's threshold and comfortable loudness
      levels. The auditory nerve's refractory properties can influence these levels due
      to high-rate stimulation with interpulse intervals within the relative refractory
      period. Recovery functions were investigated at 84 stimulation sites in 14
      Nucleus CI24 recipients using neural response telemetry and a modified forward
      masking technique. This technique introduces a reference masker-probe interval
      (MPI). In our study, an appropriate value between 300 and 375 micro s was
      determined for this reference MPI, and the use of a reference MPI of 300 micro s
      is suggested for recovery and amplitude growth functions. A median absolute
      refractory period of about 390 micro s and a median time constant of about 425
      micro s were obtained by fitting an exponential model to the data. Hence, the
      auditory nerve is usually in relative refractory state when standard neural
      response telemetry forward masking is selected because of its default MPI of 500
      micro s. This can bias the measurement of ECAP thresholds. Additionally, the
      shape of standard forward masking recovery functions was explained by the
      influence of latency shift of the neural response.

PMID- 17008775
TI  - Clinical and morphologic features of the congenitally unicuspid acommissural
      stenotic and regurgitant aortic valve.
AB  - Five adults, aged 30-75 years, are described with stenotic and regurgitant
      unicuspid acommissural aortic valves. Because none of these patients had
      clinical, echocardiographic or hemodynamic evidence of mitral valve disease, a
      case is made that these valves were congenitally malformed and not the result of
      an acquired condition.

PMID- 17008776
TI  - Parathyroid development and the role of tubulin chaperone E.
AB  - The development of the parathyroid glands involves complex embryonic processes of
      cell-specific differentiation and migration of the glands from their sites of
      origin in the pharynx and pharyngeal pouches to their final positions along the
      ventral midline of the pharyngeal and upper thoracic region. The recognition of
      several distinct genetic forms of isolated and syndromic hypoparathyroidism led
      us to review the recent findings on the molecular mechanisms of the development
      of the parathyroid glands. Although far from being understood, a special emphasis
      was given to the possible role of tubulin chaperone E (TBCE), which was
      implicated in the pathogenesis of the hypopathyroidism, retardation and
      dysmorphism (HRD) syndrome. The novel finding that TBCE plays a critical role in
      the formation of the parathyroid opens a novel domain of research, not
      anticipated previously, into the complex process of parathyroid development.

PMID- 17008777
TI  - Insulin-like growth factor delivery across the blood-brain barrier. Potential use
      of IGF-1 as a drug in child neurology.
AB  - BACKGROUND: Recent data indicate that insulin-like growth factor-1 (IGF-1) can
      cross the blood-brain barrier when bound to binding proteins. IGF-1 is very
      important for early brain development, myelination and survival of cerebellar
      neurons. It is antiapoptotic and is important for synaptic development. The aim
      of this study was to identify neurological conditions with low CNS IGF-1.
      METHODS: Levels of CSF IGF-1 were determined by radio-immunoassay (Mediagnost,
      Tubingen, Germany). RESULTS: Levels of CSF IGF-1 were low in some progressive
      diseases of white matter and the cerebellum. In some other diseases not involving
      cerebellum or white matter, CSF IGF-1 was normal. CONCLUSIONS: Our findings might
      pave the way for rational therapy in patients with neurodegeneration. Patients
      with low CNS IGF-1 might be candidates for IGF-1 therapy.

PMID- 17008778
TI  - Autoimmune cholangitis presented as fever of unknown origin.
AB  - Autoimmune cholangitis is a rare chronic cholestatic liver disease. Fever of
      unknown origin is defined as a temperature higher than 38.3 degrees C that lasts
      for more than 3 weeks with no obvious source despite appropriate investigation.
      We describe the case of a 62-year-old woman who presented with fever, fatigue and
      weight loss. The serum biochemical study showed an increase in alkaline
      phosphatase and gamma-glutamyl transpeptidase levels. Antinuclear,
      antimitochondrial, anti-smooth-muscle antibodies and antibodies against the
      cytoplasm of neutrophils were negative. Liver biopsy was compatible with
      autoimmune cholangitis. The patient was successfully treated with
      methylprednisolone and ursodeoxycholic acid. We describe here a rare case of
      fever as preceding and leading symptom of autoimmune cholangitis.

PMID- 17008779
TI  - Synergism of CAY-1 with amphotericin B and itraconazole.
AB  - BACKGROUND: CAY-1 is a fungicidal saponin from cayenne pepper whose mode of
      action differs from amphotericin B (AB) and itraconazole (IT). This work
      determined CAY-1 synergism with AB or IT. METHODS: CAY-1 was purified and used in
      checkerboard microdilution studies where CAY-1 and AB or IT were mixed with
      nongerminated (NG) and germinating (G) conidia of three Aspergillus species and
      Candida albicans. Inhibition was visually determined at 24 and 48 h. RESULTS: CAY
      1 had predominantly additive-synergistic interaction with AB or IT against the
      Aspergillus NG and G conidia. Excellent synergy between CAY-1 and AB occurred at
      24 and 48 h against C. albicans. Results suggest CAY-1 enhances AB and IT
      efficacy.

PMID- 17008780
TI  - In vitro and in vivo antiplasmodial activity of Momordica balsamina alone or in a
      traditional mixture.
AB  - BACKGROUND: Because of the dramatic situation of malaria in Africa, there is an
      urgent need to find new and cheap drugs, such as herbal medicines. Here we report
      the study of the in vitro and in vivo antimalarial activity of Momordica
      balsamina alone or in a traditional mixture used in Niger. METHODS: Extracts were
      obtained with different solvents and tested in vitro on Plasmodium falciparum and
      in vivo on Plasmodium vinckei. RESULTS: The best extracts are methanolic and
      present promising results in vivo by intraperitoneal and oral administration.
      CONCLUSION: The antimalarial activity of M. balsamina, traditionally used in
      Niger, is confirmed in vitro and in vivo without any toxicity in healthy mice.

PMID- 17008781
TI  - Urinary bactericidal activity of oral antibiotics against common urinary tract
      pathogens in an ex vivo model.
AB  - BACKGROUND: In this investigation, the urine samples obtained in a single oral
      dose pharmacokinetic study were examined for their bactericidal activity against
      a range of relevant urinary tract pathogens. METHODS: Six healthy volunteers
      received a single oral dose of ten oral antibiotics available in Croatia. Urine
      samples were taken every 2 h during the whole dosing interval of the particular
      antibiotic. The urinary bactericidal activity was tested by determination of
      urinary bactericidal titers. RESULTS: All antibiotics showed a significant
      urinary bactericidal activity against non-extended spectrum beta-lactamase
      Escherichia coli and Proteus mirabilis. Fluoroquinolones displayed high and
      persisting levels of urinary bactericidal activity against all gram-negative
      bacteria and Staphylococcus saprophyticus. CONCLUSIONS: Average urinary
      bactericidal activity can be predicted from in vitro susceptibility testing, but
      we expect that there will be patients with a low level of urinary bactericidal
      activity.

PMID- 17008782
TI  - Responses of the rat medullary neurons to central penicillin microinjection.
AB  - BACKGROUND: The microinjection of penicillin in the medulla oblongata caused
      different alterations in the global respiratory output. The purpose of this paper
      was to study the involvement of impulse activity and the functional relationship
      of bulbar neurons in mechanisms underlying experimentally induced respiratory
      arrhythmias. METHODS: Extracellular activity of neurons and diaphragmatic
      electromyogram activity were recorded and analyzed. RESULTS: Penicillin
      microinjection increased the mean discharge rate of bulbar neurons and caused the
      prolongation of discharge of inspiratory neurons. Cross-correlation analysis
      revealed new excitatory connections between neurons and a high level of positive
      synchronization of neuronal activity. CONCLUSION: The local blockage of synaptic
      inhibition by penicillin within respiratory areas leads to drastic changes in the
      functioning of neuronal elements of the single respiratory network.

PMID- 17008783
TI  - Comparison between molecular epidemiology, geographical regions and drug
      resistance in Mycobacterium tuberculosis strains isolated from Iranian and Afghan
      patients.
AB  - The aim of this study was to determine the prevalence of drug-resistant
      tuberculosis (TB) and its associated risk factors. The susceptibilities of
      Mycobacterium tuberculosis isolates were tested against four first-line
      antituberculous drugs and were typed by spoligotyping. Spoligotyping of M.
      tuberculosis strains resulted in 95 different patterns that were divided into
      three evolutionary groups (1-3). Eighty-six (90%) of the isolates had unique
      patterns that were reported for the first time. Interestingly, 9.4% of the
      strains belonged to the Beijing family. Multidrug resistance (MDR) was seen in
      group 1 of the evolutionary scenario. All M. tuberculosis isolates belonging to
      the Beijing family were associated with a resistance pattern. MDR was much higher
      in bacteria isolated from Afghan TB patients residing in Iran.

PMID- 17008784
TI  - The future in diagnosis and staging of lung cancer. Molecular techniques.
AB  - Lung cancers at the same stage of disease have markedly different rates of
      disease progression. In this review, we will address current molecular techniques
      which provide new opportunities according to diagnosis, prediction of survival or
      selection of therapy. New molecular techniques might be helpful in TNM staging
      and lead to additional individual prognostic information. A revised TNM system
      could include a TNM component and a molecular supplemental component allowing new
      markers to be evaluated without undermining the value of classic TNM staging.
      Furthermore, molecular techniques might be helpful in the early or differential
      diagnosis of lung cancer. Since many new targeted agents are effective only if
      their respective molecular markers are mutated or expressed at sufficient levels,
      DNA-based or RNA-based techniques have the potential to influence treatment
      selection in the future. Overall, we can expect that molecular markers will
      contribute to a more personalized lung cancer treatment.

PMID- 17008785
TI  - Respiratory muscle function in a large cohort of healthy subjects: can strength
      predict endurance?

PMID- 17008786
TI  - EBUS: a new dimension in bronchoscopy. Of sounds and images--a paradigm of
      innovation.

PMID- 17008787
TI  - Comparison between compliance of fluticasone propionate diskhaler and of
      fluticasone propionate diskus in adult bronchial asthma patients.
AB  - BACKGROUND AND OBJECTIVES: Because inhaled corticosteroids (ICS) play a central
      role in the management of asthma, new drug delivery systems for fluticasone
      propionate, Diskhaler (FPdh) and Diskus (FPdk), were developed. However, few
      studies have focused on compliance with these drug delivery systems, which can
      influence drug efficacy. Hence, we compared compliance with FPdk versus that with
      FPdh. METHODS: Data were obtained from a survey of pharmacists dispensing anti
      asthmatic drugs to adult asthma patients who visited participating pharmacies
      between October 2002 and November 2003. Patients were limited to regular users of
      FPdh or FPdk whose medication had not been changed for >6 months before the
      survey. Compliance and daily administration frequency of ICS were evaluated on
      the basis of pharmaceutical records. Data on asthma status and various other
      factors affecting ICS compliance were obtained by questionnaire. RESULTS: Data
      were acquired on 337 patients. There were no significant differences in gender,
      age, and duration between the FPdk and FPdh groups. Although FPdk compliance was
      significantly higher than that of FPdh, conversely there was no significant
      difference in daily dose and administration frequency between the 2 groups.
      Furthermore, there was no significant difference in the rate of concomitant drug
      and in various influencing factors associated with drug compliance. Regarding
      compliance of concomitant drug, that of oral sustained-released theophylline was
      significantly lower in FPdk versus FPdh users. CONCLUSION: In the area of drug
      compliance, FPdk is superior to FPdh. Although the reason for this is unclear, it
      is probably due to the characteristics of FPdk itself.

PMID- 17008788
TI  - Hemothorax following administration of intrapleural alteplase.

PMID- 17008789
TI  - Quantitative thin-section CT analysis of the enlargement and coalescence of low
      attenuation clusters in patients with emphysema.
AB  - BACKGROUND: The analysis of the number and size of low-attenuation clusters has
      been adopted as quantitative computed tomography (CT) analysis of emphysema;
      however, a detailed examination has not been made on the relation between the
      number of various cluster sizes and the extent of emphysema. OBJECTIVE: The aim
      of this study was to evaluate the relationship between the size and number of
      clusters on CT scans in patients with emphysema. METHODS: This retrospective
      study included 31 emphysema patients. The number (LAN) and mean size (LAS) of
      clusters below -950 HU, and relative low-attenuation area below -950 HU (RA950)
      were calculated using an image-processing program. The size of clusters was
      divided into 3 categories, and the number in each size category was obtained as
      follows: small (sLAN 0.4-8 mm(2)), medium (mLAN 8.4-40 mm(2)), and large (lLAN
      >40 mm(2)). The relationships between the RA950 and sLAN, mLAN, or lLAN were
      evaluated. Patients were divided according to the extent of RA950 (>25% = severe
      emphysema, <25% = mild emphysema), and the relations between RA950 and LAN, and
      between RA950 and sLAN, mLAN, or lLAN were evaluated. RESULTS: The sLAN decreased
      as RA950 increased (r = -0.477), whereas mLAN and lLAN increased (r = 0.421, and
      r = 0.819). In severe emphysema, sLAN and mLAN decreased as RA950 increased (r = 
      0.722, and r = -0.698). In mild emphysema, mLAN and lLAN increased as RA950
      increased (r = 0.732, and r = 0.972). CONCLUSIONS: The degree of the coalescence
      of the clusters depends on the size of clusters and the extent of emphysema.
      Quantitative CT analyses of clusters are helpful to elucidate the pathophysiology
      and progressive nature of emphysema.

PMID- 17008790
TI  - Efficacy of S-1 for patients with peritoneal metastasis of gastric cancer.
AB  - BACKGROUND: This study was designed to examine the efficacy and compliance of S-1
      for the patients with peritoneal metastasis of gastric cancer. METHODS: Sixteen
      consecutive patients with peritoneal metastasis of gastric cancer were treated
      with S-1. Their survival was compared with that of the historical control group
      (25 patients). Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine
      phosphorylase and orotate phosphoribosyl transferase mRNA expression in the tumor
      were evaluated. RESULTS: The median survival time of S-1-treated patients was 550
      days, which was significantly longer than that of the historical control group
      (215 days). We elucidated some factors to prolong the survival of the patients
      treated with S-1 for peritoneal metastasis: peritoneal metastasis without other
      distant metastases, the combination of S-1 treatment and gastrectomy, and low
      expression of thymidine phosphorylase mRNA in primary tumors. CONCLUSIONS: S-1
      showed a surprisingly long-term survival with minimum toxicity in patients with
      peritoneal metastasis of gastric cancer.

PMID- 17008792
TI  - Evaluation on scolicidal efficacy of propolis.
AB  - BACKGROUND: Propolis is a resinous material collected by bees from various
      plants. It has antimicrobial, antioxidative, immunostimulative, and regenerative
      properties. We determined the scolicidal effect of propolis in different
      concentrations and various exposure times. MATERIALS AND METHODS: Tubes
      containing Echinococcus granulosus protoscoleces were supplemented with different
      concentrations of ethyl alcohol extract of propolis. At the end of the incubation
      times, viability of protoscoleces was assessed by trypan blue exclusion test. We
      also applied 5 ml of 1 microg/ml propolis intraperitoneally for determination of
      side effects and mortality rates. RESULTS: We determined that 1 microg/ml
      concentration of propolis killed all of the protoscoleces at the end of the 3rd
      minute. In the in vivo part of the study, intraperitoneal application of propolis
      did not cause any side effects or mortality. CONCLUSION: We concluded that this
      natural agent can be used as a potent scolicidal agent after studies which will
      determine in vivo efficacy and the effects on liver and biliary tree when
      injected directly into the common bile duct.

PMID- 17008791
TI  - In vitro induction of apoptosis in U937 cells by perillyl alcohol with
      sensitization by pentoxifylline: increased BCL-2 and BAX protein expression.
AB  - BACKGROUND: Chemotherapy is effective against a wide variety of tumor cells,
      although its use is limited by side effects. In vitro experiments and phase I and
      II trials have shown that phytochemicals such as perillyl alcohol (P-OH) have
      antitumor effects. Pentoxifylline (PTX), a synthetic methylxanthine used mainly
      to treat pathologies associated with hematological diseases, sensitizes tumor
      cells to chemotherapy. The aim of this study was to determine whether PTX
      amplifies the antitumor effects of P-OH in U937 human myelomonocytic leukemia
      cells. METHODS: Apoptosis was measured by the loss of mitochondrial membrane
      potential determined by flow cytometry using dihexyloxacarbocyanine iodide
      (DiOC6) and propidium iodide. Bcl-2 and Bax protein expression was also assessed
      by Western blot analysis. RESULTS: P-OH and PTX induced loss of the mitochondrial
      membrane potential in U937 cells in vitro. Culturing the cells in the presence of
      both compounds caused a significant increase (p < 0.001) in apoptosis and
      expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins. However,
      despite their coexistence, Bax expression prevailed in our experiments. These
      data suggest that the effects of PTX might be attributable to changes in the
      mitochondrial membrane potential. CONCLUSION: PTX sensitizes tumor cells to the
      anti-neoplastic action of P-OH. These observations may have clinical relevance in
      the treatment of cancer patients.

PMID- 17008793
TI  - Changes in lung function and respiratory muscle strength after sternotomy vs.
      laparotomy in patients without ventilatory limitation.
AB  - A relevant ventilatory defect occurs after sternotomy, a very common thoracic
      surgical opening. The mechanism of the ventilatory impairment is unclear.
      Moreover, until now, the effect of sternotomy on pulmonary gas exchange has
      scarcely been investigated. We evaluated the time-course up to recovery and
      changes in spirometry, maximum static inspiratory (PI(max)) and expiratory
      (PE(max)) mouth pressures and pulmonary gas exchange in 6 patients after
      sternotomy and in 8 patients after laparotomy. All patients were free of
      cardiopulmonary diseases and had normal preoperative lung function. Sternotomy
      and laparotomy decreased forced vital capacity (FVC) by 67 and 49%, respectively.
      Moreover, the percent decreases in PI(max), PE(max) and PaO(2) after sternotomy
      vs. laparotomy were respectively 54 vs. 57%, 54 vs. 60%, and 22.6 vs. 7.5% (p <
      0.05). Following sternotomy, the percent decreases in FVC correlated with the
      percent decreases in PI(max) (p < 0.05) and PE(max) (p < 0.01). The return to
      baseline values occurred after approximately 2 weeks. The present study shows
      that sternotomy can induce greater respiratory effects than laparotomy and
      suggests a relevant involvement of respiratory muscle weakness after surgical
      opening of the thorax. The study also supports the view that the evaluation of
      patient's lung function before sternotomy can be clinically relevant.

PMID- 17008794
TI  - Prevention and treatment of type 2 diabetes in youth.
AB  - Parallel to the increase in obesity worldwide, there has been a rise in the
      prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents. The
      etiology of T2DM in youth, similar to adults, is multifactorial including genetic
      and environmental factors, among them obesity, sedentary lifestyle, family
      history of the disease, high-risk ethnicity and insulin resistance phenotype
      playing major roles. Treatment of T2DM should not have a glucocentric approach;
      it should rather target improving glycemia, dyslipidemia, hypertension, weight
      management and the prevention of short- and long-term complications. Prevention
      strategies, especially in high-risk groups, should focus on environmental change
      involving participation of families, schools, the food and entertainment
      industries and governmental agencies. Presently, limited pharmacotherapeutic
      options need to be expanded both for childhood T2DM and obesity. The coming
      decades will prove very challenging for healthcare providers battling
      socioeconomic waves conducive to obesity and T2DM. Evidence-based research and
      clinical experience in pediatrics, possibly modeled after adult trials, need to
      be developed if this public health threat is to be contained.

PMID- 17008795
TI  - Morphologic, phenotypic and functional characteristics of endothelial cells
      derived from human hepatic cavernous hemangioma.
AB  - BACKGROUNDS/AIMS: The pathogenesis of cavernous hemangiomas is largely unknown,
      and it is speculated that abnormal vasculogenesis and angiogenesis may be
      involved. In this study, the characteristics of cavernous hemangioma endothelial
      cells (CHECs) derived from the human liver were analyzed in terms of morphology,
      phenotype and function and compared with human liver sinusoidal endothelial cells
      (LSECs). METHODS AND RESULTS: By transmission electron microscopy, abnormally
      expanded endoplasmic reticulum (ER) and similarly arranged cytoplasmic vacuoles
      were only found in CHECs. Phenotypic analysis showed that the expression of
      alphavbeta3 was significantly increased in CHECs. mRNA expression of vascular
      endothelial growth factor A, and angiopoietins 1 and 2 was significantly
      increased in CHECs compared to LSECs. The functional analysis indicated that
      CHECs released more vascular endothelial growth factor A, produced significantly
      more pro-matrix metalloproteinase 2 (pro-MMP2) and activated MMP2, and exhibited
      higher procoagulant and fibrinolytic activities compared with LSECs. Confocal
      microscopy revealed that MMP2 was concentrated in some cytoplasmic granules of
      CHECs and was consistent with the distribution of expanded ER. CHECs exhibited
      more activated angiogenesis capacity and formed abnormal capillary-like
      structures in vitro. CONCLUSION: These results suggested that endothelial cells
      (ECs) derived from human cavernous hemangiomas differ from normal ECs in
      morphology, phenotype and function.

PMID- 17008796
TI  - Lack of very strong association between pre-treatment fibrinogen and PAI-1 with
      long-term mortality after coronary bypass surgery.
AB  - AIM: To explore the association between the coagulation protein fibrinogen and
      the fibrinolytic biomarker plasminogen activator inhibitor-1 (PAI-1) and the long
      term mortality after coronary artery bypass grafting (CABG). PATIENTS AND
      METHODS: In 729 patients undergoing CABG at Sahlgrenska University Hospital, a
      blood sample for fibrinogen and PAI-1 was collected prior to the procedure.
      Patients were followed for 10 years. RESULTS: Among patients with high levels of
      fibrinogen (>3.6 g/l; median), the 10-year mortality was 32.3 vs. 20.7% among
      patients with fibrinogen levels below the median (p = 0.0005). However, patients
      with higher levels of fibrinogen were older and had an adverse risk factor
      pattern. When adjusting for these differences, pre-operative fibrinogen levels
      did not clearly appear as an independent predictor of long-term mortality. The 10
      year mortality was similar in patients with high (25.3%) and low (26.5%) levels
      of PAI-1. CONCLUSION: Our results do not suggest that fibrinogen and PAI-1, when
      evaluated prior to the operative procedure, are strongly associated with
      increased mortality in the long-term after CABG, when other co-morbidity factors
      are simultaneously considered.

PMID- 17008797
TI  - Histologic assessment of right atrial appendage myocardium in patients with
      atrial fibrillation after coronary artery bypass graft surgery.
AB  - Atrial fibrillation (AF) is a common complication after coronary artery bypass
      graft (CABG) surgery. Despite the prevalence of AF occurring after cardiac
      surgery, its pathophysiology is incompletely understood. Our previous study
      demonstrated that age and left atrial enlargement were independent predictors of
      postoperative AF. Accordingly, the purpose of this study was to determine whether
      cellular changes such as fibrosis and/or hypertrophy occurred in the atrium in
      patients who subsequently developed postoperative AF. Right atrial appendage
      tissue was obtained during atriotomy in patients undergoing elective CABG
      surgery. Quantitative assessment of atrial fibrosis was performed with Sirius red
      stain, and atrial cell diameter was measured with the HE stain. Linear
      regression, t test, chi2 test or Fisher exact test were used for statistical
      analysis. Sixty-one patients (mean age 71 +/- 8 years) were studied. Increasing
      age was significantly associated with fibrosis (beta 0.3, 95% CI: 0.06-0.55, p =
      0.017). The amount of right atrial fibrosis tended to correlate with the
      incidence of postoperative AF (p = 0.08). Cell diameter was not significantly
      different between patients with versus without postoperative AF (p = 0.85). These
      results suggest that the age-related atrial fibrosis rather than cellular
      hypertrophy may be important in the pathogenesis of AF after CABG surgery and
      should be further investigated.

PMID- 17008798
TI  - Effects of enhanced external counterpulsation on carotid circulation in patients
      with coronary artery disease.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive method
      previously shown to improve measures of myocardial ischemia in patients with
      coronary artery disease. However, the concomitant effects of EECP on large and
      small arterial properties have been poorly examined. In a randomized controlled
      study, we investigated whether arterial stiffness and resistance of the carotid
      circulation are altered by EECP. METHODS: Thirty patients with angiographically
      demonstrated coronary artery disease were randomized into two groups to receive
      either 'sham' or active EECP therapy for 35 1-hour sessions. The beta stiffness
      index was calculated by the ln(Ps/Pd)/DD equation where Ps and Pd = systolic and
      diastolic blood pressure, and DD = the ratio between carotid pulse and diastolic
      diameter, measured by ultrasound sequential frames during the cardiac cycle.
      Carotid vascular resistance was calculated as the ratio between mean arterial
      pressure and mean common carotid blood flow. RESULTS: No significant between
      group differences were seen in clinical characteristics or carotid hemodynamics
      at baseline. The beta stiffness index and carotid vascular resistance were
      significantly reduced after 35 h of active EECP (p < 0.01), and the decrease was
      significantly different when compared with controls (p < 0.05 for beta stiffness
      index and p < 0.001 for carotid vascular resistance). These reductions persisted
      after multiple covariate adjustment. CONCLUSIONS: This study suggests that EECP
      exerts clear arterial effects on large and small vessels of the carotid
      circulation. The combined effects on arterial stiffness and vascular resistance
      are of particular interest in cardiovascular disease involving reduction in blood
      flow, in which techniques that increase regional blood flow may be beneficial.

PMID- 17008799
TI  - Cardiac arrhythmias and atrioventricular block in a cohort of asymptomatic
      individuals without heart disease.
AB  - AIMS: To evaluate cardiac arrhythmias and rhythm disturbances on 24 h ambulatory
      electrocardiographic monitoring in a cohort of asymptomatic healthy individuals
      with normal clinical examination. METHODS AND RESULTS: 625 asymptomatic healthy
      individuals, in the age range 15-83 (mean 42, SD 11.9) years; 276 (44.2%) men and
      349 (55.8%) women were submitted to 24-hour ambulatory electrocardiographic
      monitoring. Statistical analysis was performed with likelihood ratio test and
      automatic backward logistic regression. The frequency of atrial arrhythmias (p <
      0.0001; OR 1.059; 95% CI 1.050-1068) and of ventricular arrhythmias (p < 0.0001;
      OR 1.023; 95% CI 1.017-1.029) increased for each age increase of 1 year; neither
      atrial nor ventricular arrhythmias demonstrated a statistically significant
      difference relative to gender. Transient second-degree atrioventricular block
      (Mobitz I) was observed in 14 (2.2%) individuals and was more frequent in
      individuals with resting heart rate <60 bpm (p = 0.006; OR 6.7, 95% CI 1.7-25.5).
      CONCLUSION: The frequency of atrial and ventricular arrhythmias increased with
      age and did not demonstrate a significant difference relative to gender.
      Transient atrioventricular block was more frequent in individuals with lower
      resting heart rate.

PMID- 17008800
TI  - Perspectives in medical education-2. A blueprint for reform of medical education
      in Japan.
AB  - A blueprint for reform of medical education in Japan is presented, with the goal
      of training well rounded physicians who possess the ability to think critically
      and the clinical skill to function as generalists before they enter specialty
      training. Practical solutions are offered in three problem areas that lie at the
      heart of the shortcomings in Japanese medical education. They have to do with (i)
      the way Japanese students learn, (ii) the way Japanese teachers teach, and (iii)
      the material that students are taught. The inherently passive nature of Japanese
      students can be changed by emphasizing "active learning" and "critical thinking
      at the bedside" through a problem-oriented approach, both in the classroom and in
      the wards. Changing student learning, however, requires a commitment to teaching.
      At the present time, there is no incentive to teach at all, let alone teach in a
      constructive or interactive way. Teaching is widely perceived as a burden that
      takes time away from research, rather than as a credible and rewarding academic
      pursuit. Thus, promotion policies must be altered to reward teachers and accord
      teaching its rightful place as a primary function of the faculty. Finally, the
      introduction of active learning and interactive teaching depends on reducing the
      current emphasis on didactic instruction, which is passive and unidirectional.
      Thus, medical school curricula must be restructured to emphasize a problem
      oriented, organ system-based approach throughout medical school, starting from
      the preclinical years. Reforms in all three areas must be implemented in concert
      for them to succeed.

PMID- 17008801
TI  - Duodenal carbonic anhydrase: mucosal protection, luminal chemosensing, and
      gastric acid disposal.
AB  - The duodenum serves as a buffer zone between the stomach and jejunum. Over a
      length of only 25 cm, large volumes of strong acid secreted by the stomach must
      be converted to the neutral-alkaline chyme of the hindgut lumen, generating large
      volumes of CO2, which the duodenum then absorbs. The duodenal mucosa consists of
      epithelial cells connected by low-resistance tight junctions, forming a leaky
      epithelial barrier. Despite this high permeability, the epithelial cells, under
      intense stress from luminal mineral acid and highly elevated P(CO2), maintain
      normal functioning. Furthermore, the duodenum plays an active role in foregut
      acid-base homeostasis, absorbing large amounts of H+ and CO2 that are recycled by
      the gastric parietal cells. Prompted by the high expression of cytosolic and
      membrane carbonic anhydrase (CAs) in duodenal epithelial cells, and the
      intriguing observation that CA activity appears to augment cellular acid stress,
      we formulated a novel hypothesis regarding the role of CA in duodenal acid
      absorption, epithelial protection, and chemosensing. In this review, we will
      describe how luminal CO2/H+ traverses the duodenal epithelial cell brush border
      membrane, acidifies the cytoplasm, and is sensed in the subepithelium.

PMID- 17008802
TI  - Large-scale correlation of DNA accession numbers to the cDNAs in the FANTOM full
      length mouse cDNA clone set.
AB  - Oligonucleotide-based microarrays, such as GeneChip, are widely used to determine
      the large-scale gene expression profiles. However, GeneChip only provides
      information on the identity of the molecules, and the investigator must obtain
      each cDNA clone for further analyses. In this study, we devised a program which
      enables us to correlate a large number of DNA accession numbers to the FANTOM
      (functional annotation of the mouse) full-length mouse cDNA clone set, and made a
      correlative table between mouse GeneChip clones and FANTOM clones. This allows
      easy identification of the corresponding FANTOM clone for each GeneChip clone,
      even if the sequence of the GeneChip clone does not directly match the FANTOM
      clone. Using this table, for example, a large number of in situ hybridization
      probes can be synthesized easily, because the FANTOM clones are flanked by T3/T7
      promoters on both ends. In addition, we further developed a program which
      retrieves the amino acid sequence (AA Seq) for each clone, even for the FANTOM
      clones that lack the AA Seq description, and classifies the proteins
      automatically. As an example, we devised a correlation table with predictions of
      the secretory or transmembrane molecules. The correlation table is useful for a
      large-scale screening of molecules involved in cell-cell communication in various
      biological processes. The full correlation table for the GeneChip clones is
      available at http://www.kjm.keio.ac.jp/past/55/3/correlation_table1.html.

PMID- 17008804
TI  - A new global perspective of evidence-based wound protocols.

PMID- 17008803
TI  - Induction therapy with twice-daily interferon-beta does not improve the
      therapeutic efficacy of consensus interferon monotherapy for chronic hepatitis C.
AB  - We examined therapeutic superiority of induction therapy with twice-daily IFN
      beta (3X2=6 million units/day) onto 6-months consensus interferon monotherapy for
      chronic hepatitis C. Patients were randomly assigned to monotherapy without
      (group I, n=16) and with induction therapy (group II, n=12). The mean age of
      group II was older than that of group I, and other baseline condition was not
      statistically significant. Sustained virological response (SVR) rates of group I
      and II were 81.3% (13/16) and 58.3% (7/12), respectively (p=0.365). SVR rates in
      patients with genotype 1b were 66.7% (4/6) and 0% (0/2, because of drop-out), and
      those with high viral load were 70% (7/10) and 75% (6/8) in group I and II,
      respectively (p=1.000). Drop-out rates during therapy were 6.3% (1/16) and 33.3%
      (4/12) in group I and II, respectively (p=0.176). Age less than 50 years was the
      only independent factor that was shown by multivariate logistic model analysis to
      be associated with a sustained virological response. Although randomization
      failed to produce and equal age distribution in the two groups in this study, our
      results suggest that induction therapy with twice-daily IFN-beta has no
      beneficial effect on the efficacy of monotherapy with consensus interferon,
      probably because of the higher drop-out rates and incidence of adverse reactions
      with induction therapy.

PMID- 17008811
TI  - Voicing opinions on local coverage determinations: part II.

PMID- 17008812
TI  - Pressure mapping: seeing the invisible.

PMID- 17008813
TI  - Wound care in Tanzania at the Regional Dermatological Training Centre.

PMID- 17008814
TI  - Evaluation of clinical effectiveness of MIST ultrasound therapy for the healing
      of chronic wounds.
AB  - OBJECTIVES: (1) To determine the incidence of wound closure for chronic
      nonhealing lower extremity wounds of various etiologies using MIST ultrasound
      therapy, a 510(K)-approved, low-frequency, noncontact ultrasound device indicated
      for the cleansing and debridement of chronic wounds. (2) To determine the optimum
      treatment duration for therapy with this low-frequency, noncontact ultrasound
      device, quantifying end points that correlate with a maximal clinical response
      and identifying potential synergistic therapies that could be used in conjunction
      with this therapy. (3) To analyze the impact of low-frequency noncontact
      ultrasound therapy on the microcirculatory flow patterns within the wound bed.
      DESIGN: A noncomparative clinical outcomes trial utilizing low-frequency,
      noncontact ultrasound. SETTING: A tertiary-referral hospital-based wound clinic.
      PATIENTS: Twenty-three patients from a single tertiary-referral hospital-based
      wound clinic. Control data were obtained from a previously published,
      prospectively collected database from the same clinic. INTERVENTIONS: During an 8
      month period, a total of 29 lower extremity wounds in 23 patients who met
      criteria for inclusion were treated with low-frequency, noncontact ultrasound
      therapy. Standard of care was provided for 2 weeks for all wounds screened for
      the study. A failure to achieve an area reduction greater than 15% qualified the
      patient for enrollment to the trial and the addition of low-frequency, noncontact
      ultrasound therapy to the current treatment regimen. MAIN OUTCOME MEASURES: Wound
      healing, area and volume reduction, and laser Doppler-derived mean voltage (a
      marker for microcirculatory flow) are the main outcome measures for the study.
      RESULTS: Overall, 69% of the wounds in the study were healed using an intent-to
      treat model. When low-frequency, noncontact ultrasound was used as a stand-alone
      device, median time to healing was 7 weeks. Historic controls were healed with a
      median time to healing of 10 weeks; however, a statistically significant number
      of these patients required wound-related hospitalization and surgical procedures
      to achieve closure compared with the wounds in the present study. CONCLUSIONS:
      Treatment with low-frequency, noncontact ultrasound achieved healing in chronic
      wounds when used as a stand-alone device or in combination with moist wound care
      in 69% of cases. Response to low-frequency, noncontact ultrasound was evident
      within 4 weeks of therapy. Earlier transition to secondary procedures and
      decreased utilization of inpatient care might result in more cost-effective wound
      healing than the current standard of care. A well-designed health economic-based
      trial is warranted to assess this technology.

PMID- 17008815
TI  - Increased bacterial burden and infection: the story of NERDS and STONES.
AB  - PURPOSE: The purpose of this article is to provide practitioners with an overview
      of wound infection/inflammation and bacterial balance and to offer a guide to
      assessment and treatment of chronic wounds. TARGET AUDIENCE: This continuing
      education activity is intended for physicians and nurses who assess and treat
      wound infections. OBJECTIVES: After reading this article and taking this test,
      the participant should be able to: 1. Discuss factors associated with infection
      of the chronic wound, including the concept of bacterial balance and burden. 2.
      Identify signs of infection in the chronic wound and applicable diagnostic tests.
      3. Describe appropriate treatment for the infected chronic wound.

PMID- 17008817
TI  - Warriors versus worriers: the role of COMT gene variants.
AB  - Behavioral phenotypes are generally complex, reflecting the action of multiple
      different genes. Nevertheless, there is growing evidence that key gene variants
      can alter activity within specific neuronal circuits and, therefore, influence
      particular cognitive-affective phenomena. One example is the catechol-O
      methyltransferase (COMT) gene, which has a common variant at codon 158. Those
      with valine (Val158) alleles have increased greater COMT activity and lower
      prefrontal extracellular dopamine compared with those with the methionine
      (Met158) substitution. Val158 alleles may be associated with an advantage in the
      processing of aversive stimuli (warrior strategy), while Met158 alleles may be
      associated with an advantage in memory and attention tasks (worrier strategy).
      Under conditions of increased dopamine release (eg, stress), individuals with
      Val158 alleles may have improved dopaminergic transmission and better
      performance, while individuals with Met158 alleles may have less efficient
      neurotransmission and worse performance. Some evidence suggests that Val158
      alleles are associated with schizophrenia, while Met158 alleles are associated
      with anxiety.

PMID- 17008818
TI  - Potential markers for problematic internet use: a telephone survey of 2,513
      adults.
AB  - OBJECTIVE: The Internet has positively altered many aspects of life. However, for
      a subset of users, the medium may have become a consuming problem that exhibits
      features of impulse control disorders recognized in the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition. METHOD: This is the first
      large-scale epidemiological study of problematic Internet use through a random
      digit-dial telephone survey of 2,513 adults in the United States. Given the lack
      of validated criteria, survey questions were extrapolated from established
      diagnostic criteria for impulse control disorders, obsessive-compulsive disorder,
      and substance abuse. Four possible diagnostic criteria sets were generated. The
      least restrictive set required the respondent to report an unsuccessful effort to
      reduce Internet use or a history of remaining online longer than intended,
      Internet use interfering with relationships, and a preoccupation with Internet
      use when offline. RESULTS: The response rate was 56.3%. Interviews averaged 11.3
      minutes in duration. From 3.7% to 13% of respondents endorsed > or =1 markers
      consistent with problematic Internet use. The least restrictive proposed
      diagnostic criteria set yielded a prevalence of problematic Internet use of 0.7%.
      CONCLUSION: Potential markers of problematic Internet use seem present in a
      sizeable proportion of adults. Future studies should delineate whether
      problematic Internet use constitutes a pathological behavior that meets criteria
      for an independent disorder, or represents a symptom of other psychopathologies.

PMID- 17008819
TI  - A poor metabolizer for cytochromes P450 2D6 and 2C19: a case report on
      antidepressant treatment.
AB  - Scientific literature has never described a poor metabolizer for both the
      cytochrome P450 (CYP) 2D6 and the CYP 2C19. They are expected to be rare (<1% in
      different ethnic groups) and prone to adverse drug reactions with many
      antidepressants. In an ongoing pharmacogenetic study, after genotyping 1,576
      subjects in three Kentucky state hospitals we have found one poor metabolizer for
      both CYP 2D6 and CYP 2C19, which corresponds to a prevalence of 0.06% (95% CI
      0.01 to 0.36). The naturalistic antidepressant treatment of this poor metabolizer
      for both enzymes is described in this article. As genotyping reaches clinical
      practice, it will be interesting to prospectively establish whether mirtazapine
      is a reasonable choice as an antidepressant for these patients, as the data and
      this case suggest.

PMID- 17008820
TI  - What is the optimal way to subdivide obsessive-compulsive disorder?
AB  - The clinical presentation of obsessive-compulsive disorder (OCD) varies not only
      across patients but over the course of the disorder. This diversity indicates
      that OCD is a heterogeneous disorder, which may have an important impact on
      psychopathological, longitudinal, genetic, and treatment research. To better
      understand OCD heterogeneity, more homogeneous phenotypic descriptions are
      necessary to delimiting clinically meaningful subgroups of patients. Besides
      phenotypic descriptions, another method of delimiting OCD patient subgroups
      includes the search for endophenotypes (extended phenotypes) based on
      neurophysiological, immunological, genetic, neuropsychological, or neuroanatomic
      (neuroimaging) paradigms. This article will describe some strategies that deal
      with OCD heterogeneity, including the identification of more homogeneous
      phenotypical categories, an improved understanding of obsessive-compulsive
      symptom dimensions and how to use them as quantitative traits, and broadening the
      diagnostic boundaries of OCD to include other related conditions. The relevance
      and limitations of each approach are also discussed. Since the etiological
      mechanisms associated with the expressions of OCD are unknown, there is probably
      not one but several heuristic strategies to search for more homogeneous OCD
      subgroup, that combined may provide the most fruitful results.

PMID- 17008821
TI  - A pilot survey of inmate preferences for on-site, visiting consultant, and
      telemedicine psychiatric services.
AB  - OBJECTIVE: To assess inmate preferences for in-prison mental health services,
      outside psychiatric consultants, and telemedicine psychiatric consultation for 16
      mental health services. METHODS: Structured interviews were conducted of the
      service modality preferences of 28 inmates who received psychiatric telemedicine
      consultations in New York State Department of Corrections facilities. RESULTS:
      For five of the 16 mental health services assessed, a significantly larger
      proportion of inmates preferred delivery of mental services by their on-site
      mental health team to an outside psychiatric consultant, whether visiting or
      using telemedicine. For another eight services, inmate preferences were
      approximately equal. For three services (treatment progress, evaluation of
      childhood sexual abuse, and sexual concerns), inmates reported a trend toward
      preference for outside consultation (visiting and telemedicine combined). For no
      service did inmates prefer telemedicine to a visiting consultant. CONCLUSION:
      Although inmates prefer the use of on-site mental health professionals for many
      mental health services, some inmates prefer visiting or telemedicine consultants
      for the evaluation of safety and sexual issues. Because telemedicine is efficient
      and readily available, its role in these areas requires further evaluation.

PMID- 17008822
TI  - The use of antiepileptic drugs in bipolar disorders: a review based on evidence
      from controlled trials.
AB  - Antiepileptic drugs (AEDs) have diverse psychotropic profiles. Some AEDs have
      proven to be efficacious in the treatment of mood disorders, especially bipolar
      disorder. Others are ineffective as primary treatments but may be useful adjuncts
      for mood disorders or comorbid conditions. Valproate (acute mania and mixed
      episodes), carbamazepine (acute mania and mixed episodes), and lamotrigine
      (maintenance to delay recurrence) have United States Food and Drug Administration
      indications for the treatment of bipolar disorder. This article provides an
      overview of data on the use of AEDs in bipolar disorder, including acute mania
      and depression, prophylaxis, and rapid cycling.

PMID- 17008823
TI  - History and pathophysiology of ADHD.

PMID- 17008825
TI  - Recent advances in the understanding and treatment of anxiety disorders.
      Resilience: determinants, measurement, and treatment responsiveness.
AB  - In human terms, resilience is an ability to cope with stress and varies with
      context, time, age, gender, and cultural origin. Resilience shifts the focus of
      psychological investigation onto increasing the positive rather than reducing the
      negative. Inquiry into resilience has evolved from descriptions of resilient
      qualities, to discovery of the process to attain resilience, to uncovering the
      motivation to reintegrate in a resilient manner. Much of the research on
      resilience has focused on children in settings such as family violence, extreme
      poverty, war, and natural disasters. A coherent pattern of characteristics
      associated with successful adaptation has emerged. Salient characteristics
      include commitment, dynamism, humor in the face of adversity, patience, optimism,
      faith, and altruism. As such, resilience may represent an important target of
      treatment in anxiety, depression, and stress reactions. Resilience can be
      quantified, but available measures need to be validated transculturally. There
      exist many possible determinants of resilience, including neurobiologic, genetic,
      temperament, and environmental influences. Resilience is modifiable on individual
      and cultural levels. Posttraumatic stress disorder is an example of a serious
      disorder associated with impaired stress coping that can improve with treatment.

PMID- 17008826
TI  - Understanding the neurobiology of comorbidity in anxiety disorders.
AB  - Anxiety and depression are common disorders that frequently co-exist. Both
      disorders show good response to antidepressants, especially the selective
      serotonin reuptake inhibitors. Some suggest that these disorders are variants of
      the same underlying brain pathology. This review examines the similarities and
      differences between anxiety and depression in terms of the known neurobiological
      etiologic mechanisms as well as their biological underpinnings and response to
      treatment. Sufficient and significant differences between these disorders support
      the view that they are independent entities. Shared abnormalities in the 5HT1A
      receptor function, for example, may help explain some of the comorbidity.

PMID- 17008827
TI  - Defining response and remission in anxiety disorders: toward an integrated
      approach.
AB  - Response and remission rates are commonly used to evaluate the efficacy of
      treatments for anxiety disorders and other psychiatric illnesses. Response is
      generally regarded as a clinically meaningful improvement in symptoms, while
      remission, the goal of treatment, is generally thought of as the absence or near
      absence of symptoms following illness, accompanied by a return to premorbid
      levels of functioning. Response and remission are often defined using psychiatric
      rating scales, based on score cutoffs or the magnitude of score changes from
      baseline. While no universally accepted criteria exist, a commonly used threshold
      for response is a >50% improvement in the total score, while for remission,
      various cutoff points have been used. Comparison of cutoffs or change scores for
      disease-specific scales with Clinical Global Impressions ratings is a useful way
      of evaluating response and remission criteria across disorders. To illustrate the
      use of disease-specific and global measures, this article summarizes data from
      randomized, placebo-controlled studies of adult patients with generalized anxiety
      disorder, social anxiety disorder, or panic disorder treated with the serotonin
      norepinephrine reuptake inhibitor venlafaxine extended release, for which acute
      phase data are available (a total of 13 trials).

PMID- 17008828
TI  - Efficacy of combined pharmacotherapy and psychotherapy versus monotherapy in the
      treatment of anxiety disorders.
AB  - Anxiety disorders in the United States are prevalent, widespread, and disabling.
      These illnesses may account for almost one third of the $148 billion total mental
      health bill each year. Pharmacologic options include tricyclic antidepressants,
      monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors,
      selective serotonin reuptake inhibitors, and anxiolytics. Psychological
      treatments include cognitive-behavioral therapy (CBT), cognitive therapy,
      exposure, and ritual prevention therapies. Despite insufficient evidence, many
      experts recommend combined treatment, generally medication with CBT. A literature
      review was conducted to examine studies with random assignment, adequate methods
      and sample sizes, blind assessments, sufficient dosages and durations of
      treatment, and satisfactory reporting of data, to determine whether combined
      treatment was superior to monotherapy. Twenty-six randomized clinical trials were
      identified; nine met review criteria. A review of relevant studies could not
      confirm the superiority of combined treatment over monotherapy. In one of four
      studies of obsessive-compulsive disorder, combined treatment produced better
      results than monotherapy. There was no evidence of superiority for combined
      therapy over monotherapy for the treatment of social phobia or generalized
      anxiety disorder. There were no studies that met review criteria for either
      specific phobia or posttraumatic stress disorder (PTSD). With panic disorder,
      there was evidence that combined treatment might actually lead to worse outcome.
      Combined treatment is commonly recommended, but empirical support is limited.
      More research is needed. There are few well-designed studies, and little data
      regarding PTSD and specific phobias.

PMID- 17008829
TI  - Evidence-based guidelines for anxiety disorders: can they improve clinical
      outcomes?
AB  - Evidence-based medicine (EBM) enables clinicians to justify decision making,
      enhances the quality of medical practice, identifies unanswered research
      questions, and ensures the efficient practice of medicine. Implementation of
      evidence-based mental health programs requires education, time, and improved
      effort by administration, regulatory, and clinical professionals. Essential to
      these efforts are consistent incentives for change, effective training materials,
      and clear clinical guidelines. Guidelines exist within the framework of EBM. Good
      guidelines are simple, specific, and user friendly, focus on key clinical
      decisions, are based on research evidence, and present evidence and
      recommendations in a concise and accessible format. Potential limitations of
      guidelines to improve clinical outcomes in anxiety disorders are the widespread
      distribution of anxiety symptoms in primary care, health inequalities across
      patient groups, persistent misconceptions regarding psychotropic drugs, and low
      confidence in using simple psychological treatments. Clinical guidelines
      generally specify therapeutic areas covered and not covered, but often there is
      no mention of cost or cost effectiveness of treatment. Guidelines can inform
      clinical decision making, but administrators of drug formularies may regard
      themselves as being primarily responsible for limiting costs and access to
      certain medications, even if these decisions are at odds with guideline
      recommendations.

PMID- 17008830
TI  - Emotional reactivity and risk for psychopathology among adolescents.
AB  - Various aspects of personality or dispositional style predict risk for
      psychiatric disorders among adults. In particular, signs of neuroticism,
      emotional reactivity, or sensitivity to stress are strong predictors of later
      mood or anxiety disorders. The current report extends this literature to
      adolescents. An epidemiologic sample of 776 young people living in upstate New
      York received psychiatric assessments based on the Diagnostic and Statistical
      Manual of Mental Disorders, Third Edition-Revised, (DSM-III-R) and a self-report
      assessment of personality style in 1983 and 1985. Psychopathology was again
      assessed in 1992. The current study first examined demographic correlates of
      emotional reactivity. The study then considered the predictive relationship
      between emotionally reactive personality style at one study wave and
      psychopathology at later waves. In middle but not early adolescence, girls showed
      higher levels of emotional reactivity than boys. In turn, high levels of
      emotional reactivity predicted a range of psychiatric disorders at follow-up. The
      most consistent associations emerged for major depression and fearful spells, a
      term the authors use to describe a subclinical form of panic attacks. As in
      adults, midadolescent girls rate themselves as more emotionally reactive than
      midadolescent boys. Moreover, adolescents who rate themselves as emotionally
      reactive face a high risk for mood and anxiety disorders. High levels of
      emotional reactivity may represent a manifestation of underlying neurobiologic
      risk for mood and anxiety disorders.

PMID- 17008831
TI  - Neural bases and development of face recognition in autism.
AB  - This paper critically examines the literature on face recognition in autism,
      including a discussion of the neural correlates of this ability. The authors
      begin by selectively reviewing the behavioral and cognitive neuroscience research
      on whether faces are represented by a "special" behavioral and neural system-one
      distinct from object processing. The authors then offer a neuroconstructivist
      model that attempts to account for the robust finding that certain regions in the
      inferior temporal cortex are recruited in the service of face recognition. This
      is followed by a review of the evidence supporting the view that face recognition
      is atypical in individuals with autism. This face-recognition deficit may
      indicate a continued risk for the further development of social impairments. The
      authors conclude by speculating on the role of experience in contributing to this
      atypical developmental pattern and its implications for normal development of
      face processing.

PMID- 17008832
TI  - Affect regulation, brain development, and behavioral/emotional health in
      adolescence.
AB  - This paper addresses the importance of affect regulation (AR) in relation to a
      broad range of behavioral and emotional health problems that emerge during
      adolescence. AR is defined as the adaptive modulation of emotional experience to
      serve a goal or purpose. This conceptualization of AR emphasizes the use of
      cognitive skills to guide, inhibit, or modify emotion and behavior, including the
      expression of emotional responses, in learned, strategic ways-skills that
      ultimately underpin adult levels of social maturity and the ability to show
      "responsible" behavior across a range of emotional situations. Neurobehavioral
      systems that subserve these AR skills include areas of the inferior and orbital
      prefrontal cortex (PFC), with rich interconnections to several limbic structures
      and other cortical areas, including the dorsolateral PFC. Adolescence represents
      an important developmental period in the functional maturation of adult AR
      skills; it is also a critical time in the development of clinical disorders of AR
      (eg, rates of depression increase dramatically and gender differences in
      depression emerge). Maturational changes in AR that occur during adolescence
      particularly with respect to the role of emotions influencing responsible
      decision making-are also relevant to understanding key aspects of the
      developmental pathways of some behavioral health problems, such as alcohol use
      and nicotine dependence. A strong case is made for developmental research in
      affective neuroscience aimed at this important maturational period, particularly
      the kind of transdisciplinary research leading toward mechanistic understanding
      of the development of adolescent-onset disorders. Improving understanding in
      these areas could ultimately lead to the development of early interventions in
      targeted high-risk populations, and has enormous clinical and social policy
      relevance.

PMID- 17008833
TI  - Sex steroids and human behavior: implications for developmental psychopathology.
AB  - In a variety of mammalian species, prenatal androgens organize brain structures
      and functions that are later activated by steroid hormones in postnatal life. In
      humans, studies of individuals with typical and atypical development suggest that
      sex differences in reproductive and nonreproductive behavior derive in part from
      similar prenatal and postnatal steroid effects on brain development. This paper
      provides a summary of research investigating hormonal influences on human
      behavior and describes how sex differences in the prevalences and natural
      histories of developmental psychopathologies may be consistent with these steroid
      effects. An association between patterns of sexual differentiation and specific
      forms of psychopathology suggests novel avenues for assessing the effects of sex
      steroids on brain structure and function, which may in turn improve our
      understanding of typical and atypical development in women and men.

PMID- 17008835
TI  - Obstructive sleep apnea and hypertension: epidemiology, mechanisms and treatment
      effects.
AB  - Obstructive sleep apnea (OSA) is a highly prevalent disorder of breathing during
      sleep. A growing body of evidence suggests that OSA is independently associated
      with an increased risk of cardiovascular disease, although the extent of this
      risk and underlying mechanisms remain to be elucidated. However, there is clearer
      evidence from epidemiological and pathophysiological research of a causal link
      between OSA and hypertension. The acute hemodynamic and autonomic perturbations
      that accompany obstructive apneas during sleep, with associated repeated arousals
      and intermittent hypoxemia, appear to result in sustained hypertension. In
      addition to the metabolic and humoral effects from obesity, OSA appears to
      predispose individuals to autonomic imbalance characterized by sympathetic
      overactivity and altered baroreflex mechanisms as well as alterations to vascular
      function. Treatment of OSA restores normal sleep architecture and generally
      mitigates the acute hemodynamic effects of OSA. Treatment of symptomatic OSA,
      particular at the severe end of the spectrum, appears to be associated with
      improvements in blood pressure, both during sleep and wakefulness, and there may
      also be additional gains in subjects who are hypertensive and/or resistant to
      antihypertensive medications. The severe group appears to be particularly at risk
      for developing fatal and non-fatal cardiovascular events and treatment with
      continuous positive airway pressure appears to markedly reduce that risk. Future
      treatment studies will need to be extended for greater than the current average
      of 1-2 months in order to more fully evaluate any time dependent improvements in
      blood pressure, and consequent cardiovascular risk.

PMID- 17008836
TI  - Renovascular hypertension: clinical concepts.
AB  - Systemic hypertension is a common disorder in clinical practice and causes
      significant morbidity and premature death. A small percentage (< 5%) of patients
      with hypertension may have renovascular hypertension. Strictly speaking, the term
      renovascular hypertension should be applied only when the blood pressure rises as
      a consequence of renal ischemia. Thus, the mere presence of renal artery stenosis
      is not synonymous with renovascular hypertension. Treatment strategies should be
      directed at ''renovascular hypertension'' rather than an anatomic renal artery
      stenosis (which may be discovered accidentally). Management of renal artery
      stenosis/renovascular hypertension is imprecise at best. This article discusses
      the patho-physiology of renovascular hypertension and how to approach a patient
      with renal artery stenosis.

PMID- 17008837
TI  - Cirrhotic portal hypertension: current and future medical therapy for primary and
      secondary prevention of variceal bleeding.
AB  - Portal hypertension (PHT) is the most common complication of chronic liver
      disease and develops in the vast majority of patients with cirrhosis. It is
      characterized by an increase of the portal vein pressure, and leads to the
      development of gastroesophageal varices, ascites, renal dysfunction and hepatic
      encephalopathy. Over the years, it has become clear that a decrease in portal
      pressure is not only protective against the risk of variceal (re)bleeding but is
      also associated with a lower long-term risk of developing other complications and
      with an improved long-term survival. At present, non-selective b-blockers remain
      the medical treatment of choice for both primary and secondary prophylaxis.
      However, recent advances in the knowledge of the pathophysiology of cirrhotic PHT
      have directed future therapy towards the increased intrahepatic vascular
      resistance, which in part is determined by an increased hepatic vascular tone.
      This increased vasculogenic component provides the motivation to the use of
      therapies aimed at increasing intrahepatic vasorelaxing capacity on the one hand
      and at antagonizing excessive intrahepatic vasoconstrictor force on the other
      hand. This review covers current and future developments in the treatment of PHT
      with regard to primary and secondary prophylaxis.

PMID- 17008839
TI  - Neuroimaging in the diagnosis of idiopathic intracranial hypertension.
AB  - Traditionally, the primary role of imaging in the diagnosis of idiopathic
      intracranial hypertension (IIH) has been to exclude other conditions that can
      cause increased intracranial pressure (ICP) and papilledema. Over the years
      multiple attempts have been made to define objective signs on cross-sectional
      imaging as well as on cerebral angiography that would actually identify IIH
      patients rather than only exclude other underlying conditions. There was also
      hope that mechanism-derived' imaging techniques such as magnetic resonance
      venography (MRV) and diffusion weighted imaging would potentially provide insight
      into the still unknown underlying etiology of this disease. It was recently shown
      in a double blind controlled study that flattening of the posterior aspect of the
      globe is the only sign on cross-sectional imaging that, if present, strongly
      suggests the diagnosis of IIH. In addition, evaluation of extra-luminal and intra
      luminal narrowing of the transverse and sigmoid dural sinuses with contrast
      enhanced MRV using a simple grading system provides a highly sensitive and
      specific test for identifying patients with IIH. Unfortunately none of the
      imaging based studies published to date can explain the pathogenesis of IIH
      whether it be a primary vascular venous disorder causing the increase in ICP or
      rather the disorder itself secondarily affecting the cerebral veins.

PMID- 17008838
TI  - Pathophysiology and medical management of systemic hypertension and pre-eclampsia
      in pregnancy.
AB  - Hypertension in pregnancy includes a group of distinct disorders that require
      special consideration in both prevention and pharmacological treatment. In recent
      years, there have been few advances regarding the pathophysiology and prevention
      of pre-eclampsia, however there have been some promising studies regarding
      possible modes of screening women for preeclampsia before clinical signs and
      symptoms are apparent. The recommendations for first-line drug therapy for the
      hypertensive complications of pre-eclampsia, and the recommendations for
      pharmacological treatment of women with chronic hypertension antedating
      pregnancy, have changed little primarily because first-line medications have the
      advantage of having had more extensive research experience. Recent clinical
      trials have demonstrated the efficacy and safety of various second-line drugs for
      the hypertensive disorders of pregnancy; whether these therapies can eventually
      replace the standard recommended medications will require more extensive long
      term investigation.

PMID- 17008840
TI  - Patient-triggered ventilation.
AB  - During patient triggered ventilation, the infant's inspiratory efforts should
      occur synchronously with ventilator inflations. Such an optimal interaction,
      however, is dependent on the performance of the triggering device and the
      ventilator and the infant's lung function. Triggered ventilation (assist control,
      A/C), synchronous intermittent mandatory ventilation (SIMV), pressure support
      ventilation (PSV), volume targeted ventilation (VTV) with A/C, SIMV, PSV or
      proportional assist ventilation (PAV) can be delivered via the endotracheal tube
      or via nasal prongs. Meta-analysis of randomised trials demonstrated that the
      only advantage of A/C/SIMV over non-triggered positive pressure ventilation was a
      shorter duration of ventilation, in particular there was no significant effect on
      the incidence of chronic lung disease. The reduction in ventilation duration,
      however, was only seen if triggered ventilation is started in the recovery stage
      rather than in the acute phase of respiratory distress syndrome. Results from
      small randomised trials have suggested that A/C rather than SIMV is a better
      weaning mode, as reduction of the SIMV rate below 20 breaths per minute increases
      the work of breathing. Other small trials have highlighted triggered ventilation
      delivered by nasal prongs may reduce extubation failure rate. Physiological
      studies have demonstrated some advantages of PSV with and without VTV and PAV,
      whether these translate into improvements in long term clinical outcomes remains
      to be tested in appropriately designed randomised trials.

PMID- 17008841
TI  - Alcohol and suicidal behavior in adolescents.
AB  - This review describes epidemiology, pathophysiology, risk factors, treatment and
      prevention of suicidal behavior in adolescents. As one of the leading causes of
      death of young adults, adolescent suicide has become a public health problem and
      an increase in the adolescent suicide rate has been observed over the past
      several decades. One important risk factor thought to contribute to the recent
      rise in suicidal behavior among young adults is increasing alcohol abuse among
      adolescents. The link between alcohol and suicide in adolescents is complicated
      and multiple risk factors are important in explaining and understanding suicidal
      behavior among adolescents. Comorbid psychopathology, which is common among
      adolescent alcohol abusers, substantially increases the risk for suicide
      behavior. Availability of alcohol and guns at home may also contribute to suicide
      risk in adolescents. Studies of stress hormones, brain neurotransmitters,
      hereditary factors, behavioral measures and gender differences shed light in
      understanding this complex phenomenon. Ideally, treatment of adolescents who
      receive a diagnosis of an alcohol use disorder and co-occurring suicidality
      should follow an integrated protocol that addresses both conditions. Future
      studies of psychological and neurobiological mechanisms of suicidality in
      adolescents with alcohol and/or substance abuse are merited.

PMID- 17008842
TI  - [Endocrine disrupters and male gonads].

PMID- 17008843
TI  - Risk behaviours among young people. Evaluation and descriptive analysis.
AB  - AIM: Risk behaviours--as they are defined by specialist literature for the damage
      these behaviours cause to young people's health and/or life--are getting more and
      more frequent among young people. They range from self-injuring behaviours to the
      consequences of a precocious, high-risk and/or promiscuous sexual activity, from
      abnormal eating behaviours to the deaths from fun. METHODS: The inquiry concerned
      a group of university students (100 males and 100 females), selected at random
      from the Faculties of Medicine and Surgery, Psychology, Economy and Jurisprudence
      of the University of Palermo, who were asked to answer a questionnaire composed
      of 91 questions and structured in 4 sections. The first section regards associate
      identifying information; the second one inquires on experiences and requirements
      concerning sexuality; the third section explores the state of health and the use
      of drugs and alcohol; the fourth section looks into relations with others.
      RESULTS: The analysis of our data revealed that young people have different high
      risk behaviours (use of drugs and alcohol, non protected sexual intercourse,
      carelessness for one's and one's partner's serological state); this is associated
      to poor information, as complained by the people interviewed, on the prevention
      of sexually transmissible diseases, use of drugs and alcohol. CONCLUSIONS: The
      conclusion is drawn that the new modalities of the assumption of risk by young
      people would correspond to the climate of vagueness, lack of limits, meanings and
      values which characterize the present society.

PMID- 17008844
TI  - Mobile phone and young people. A survey pilot study to explore the controversial
      aspects of a new social phenomenon.
AB  - AIM: Aim of this paper is to report the results of a pilot study as a part of a
      program addressed to health promotion and to improve the culture of
      sustainability in the school. METHODS: A 15-items structured questionnaire was
      administered to 1 011 students (aged 9-18 years) in order to explore the entity
      of the phenomenon of mobile telephony among the young and qualitatively esteem
      the level of exposure to the potential adverse health and social effects of such
      dominant form of electronically mediate communication. This preliminary
      information was then deepened by in-group interviews focused to clarify the
      cultural basis of the phenomenon. RESULTS: The survey-study confirmed that the
      penetration of mobile telephony among the young matches with the national trend:
      96% of 14-18-teens own at least one mobile phone; 22% of them own multiple mobile
      phones. In addition, most of them use mobile phone all the day; a third makes
      calls over 6 minutes long; half is poorly informed about the potential health
      risks related to ''electromagnetic pollution''. CONCLUSIONS: Despite the most
      perceive mobile phone like something noxious, only 23% holds it far from body; a
      very small percentage uses a hands-free kit. Most declared to suffer from a sort
      of addiction towards mobile phone. In the light of a growing literature and of a
      supposed more vulnerability of children and adolescents towards toxicants than
      adults, we believe that health and school operators should inform parents and the
      young about the possible risks linked to the abuse of technology and promote a
      more critic and responsible approach to mobile phone.

PMID- 17008845
TI  - [Short-stay observation in the Pediatric Emergency Room: a 2003-1993 comparison].
AB  - AIM: To evaluate the effectiveness of Short-Stay Observation (SSO) in the
      paediatric Emergency Room (ER) according to changes over time of guidelines.
      METHODS: This retrospective study analyses the probability of discharge
      immediately from ER or after SSO and of hospital admission in Trieste during 2003
      as compared with 1993. Subjects aged under 18 with respiratory, urinary tract,
      neurological and gastrointestinal pathologies, selected symptoms and injuries
      were studied. RESULTS: In 2003 the 86.2% of 6 350 patients enrolled in the study
      were discharged immediately, compared with the 81.7% of 5475 subjects in 1993 (RR
      1.05, IC 95% 1.04-1.07), the 10.0% were discharged after SSO, compared with the
      5.9% in 1993 (RR 1.71, IC 95% 1.50-1.95). The 3.8% of the subjects were admitted
      in 2003, compared to the 12.4% in 1993 (RR 0.30, IC 95% 0.26-0.35). The role of
      SSO was particularly significant in case of pneumonia, URI, urinary tract
      infections, seizures, gastroenteritis, abdominal pain, infant fever, injuries.
      CONCLUSIONS: The decrease of hospital admissions, pointed out in 2003, are
      related to a better choice of candidates for SSO and to changes in guidelines
      concerning the approach to urinary tract infections and seizures, the treatment
      of respiratory distress and gastroenteritis dehydration, and the early
      identification of predictors of injuries complications. The study confirms the
      effectiveness of SSO in both avoiding inappropriate admissions and reducing those
      with limited needs of hospital assistance, assuring the quality of care. The
      reduced hospital stay decreases child and his family discomfort and favours the
      care continuity due to the involvement of family paediatrician.

PMID- 17008846
TI  - Leptin levels in patients with thalassemia major.
AB  - AIM: Patients with thalassemia major often present endocrine abnormalities due to
      dysfunction in their hypothalamic-pituitary axis. Leptin, an adipocyte derived
      hormone, primarily acts in hypothalamus and its deficiency in the ob/ob mouse
      results in persistent immaturity of its hypothalamic-pituitary function. The aim
      of the study was to evaluate leptin levels in thalassemic patients. METHODS: The
      study involved 33 adult patients (11 males), mean age (SD) 19.3 years (4.4) and a
      group of 12 prepubertal boys, mean age (SD): 7 years (1.7) with homozygous beta
      thalassemia. RESULTS: Mean (SD) leptin concentration was 3.2 (3.3) ng/mL in
      thalassemic males and 8.6 (3.3) ng/mL in thalassemic females; values
      significantly lower than matched normal subjects. In the group of prepubertal
      thalassemic children, leptin levels were also lower compared with matched healthy
      children, although the difference was not statistically significant. CONCLUSIONS:
      In conclusion, low leptin levels were observed in thalassemic patients, which may
      be due to a toxic effect of iron to adipocytes.

PMID- 17008847
TI  - [First choice treatment of the pediatric wrist ganglia].
AB  - AIM: The authors analyze the anatomical, etiopathogenetic and clinical
      characteristics of ganglia of the hand and especially the radio-carpus, which
      represent the most frequent cause of wrist swelling in pediatric age. They
      underline the importance of an adequate period of clinical observation and splint
      treatment, as the first methodical choice, rather than aspiration or surgical
      immediate resection. METHODS: The experience of the authors is based on splinting
      and/or surgical treatment on a series of 15 patients with wrist ganglion, with a
      follow-up of 4 years. The period of clinical observation had never been less than
      6 months and the static splint had been recommended during nocturnal hours only,
      on a 3-4 month basis at least. RESULTS: Two thirds of the cases showed
      spontaneous re-absorption of the ganglion, while in the remaining third part a
      surgical indication of removal had been suggested, due to absence of spontaneous
      remission and the presence of trouble or pain in movements. The authors never
      practice the aspiration of the content of the ganglion, since recent literature
      advises against it due to the high percentage of recurrence observed.
      CONCLUSIONS: The clinical observation and the dedicated nocturnal splinting of
      the wrist ganglia in pediatric age represent the first treatment advocated.
      Surgery is suggested in cases unsolved with a conservative therapy. Aspiration is
      strongly discouraged.

PMID- 17008848
TI  - [Congenital hypopituitarism in agenesis of the anterior pituitary gland:
      immediate management and follow-up].
AB  - We report a case of an infant admitted to our division at 50 days of age, who
      presented acute abdomen, respiratory insufficiency, skeletal abnormalities,
      craniofacial dismorphism, low gain of weight. Despite negative at neonatal
      screening for hypothyroidism, laboratory analyses showed marked decrease of all
      pituitary hormones but ACTH, and low levels of cortisol. Magnetic resonance was
      indicative of adenohypophysis agenesis with maintained neurohypophysis. Results
      of substitutive therapy are reported.

PMID- 17008849
TI  - [A case of Listeria monocytogenes meningitis in an immunocompetent infant].
AB  - Listeria Monocytogenes meningitis is a rare affection after the neonatal period,
      but in immunocompromised patients. Listeria Monocytogenes is a Gram-positive,
      facultative intracellular bacterium frequently causing infection in pregnant
      women, in patients with cell-mediated immunity deficit and in the early and late
      stages of life. We present a case of Listeria Monocytogenes meningitis in an
      immunocompetent nomad 8-month-child, preceded by gastroenteritis. Although
      gastrointestinal symptoms may be due to intestinal infection by Listeria, the
      concomitant presence of other bacteric or viral enteric pathogens may have
      promoted bacterium intestinal translocation and generated disseminated disease.
      The main transmission route of infection after the neonatal period is ingestion
      of contaminated food. A diet history was taken after isolation of the bacterium
      in liquor and showed that the child was an eater of undercooked hot-dogs. Despite
      the frequency of clinical complication in such affection, the outcome in this
      patient was a complete recovery. Although the infection is extremely infrequent
      in healthy children, physicians should always consider Listeria as a possible
      etiologic agent of meningitis in pediatric patients, regardless of their age or
      immunological status, especially in patients living in precarious sanitary
      conditions, where weaning times and conditions are not respected and a suitable
      food cooking is not assured.

PMID- 17008850
TI  - Pyloric duplication: ultrasound appearance.
AB  - This paper reports a case of pyloric duplication, an extremely rare abnormality
      usually discovered during infancy. Clinical findings involved mainly symptoms of
      obstruction and radiological evaluation included abdominal US, plain radiography
      and CT imaging. Pyloric duplication was diagnosed by US and confirmed by CT scans
      and surgery. This case shows that when the sign of two-layer pattern is present
      in US scans, a conclusive diagnosis for alimentary tract duplications can be
      reached and there is no need for further radiological evaluation.

PMID- 17008851
TI  - [Management of hyperbilirubinemia in the newborn infant at 38 or more weeks of
      gestation].

PMID- 17008852
TI  - [Tianeptine-induced weight gain in adolescents suffering from autism].

PMID- 17008853
TI  - The use of inhaled nitric oxide in the premature infant with respiratory distress
      syndrome.
AB  - The identification of the biologic properties of nitric oxide (NO) is one of the
      key scientific discoveries of the century, but its potential for treating human
      disease is yet to be fully realized. NO has a basic role in regulating vascular
      tone of the pulmonary circulation, and recent animal models have suggested a more
      wide reaching influence on perinatal lung development. In animal models, NO has
      effects on lung growth, angiogenesis, airway smooth muscle proliferation,
      vascular remodeling, surfactant function, inflammation, and pulmonary mechanics.
      However, despite extensive basic science investigation and completion of several
      large clinical trials, the role of NO in the treatment of the premature infant
      with respiratory distress syndrome remains unclear. One must conclude that the
      interaction of lung immaturity, ventilator and oxygen-induced lung injury, and NO
      biology in the premature newborn is incompletely understood. Clinical trial
      results of inhaled NO therapy in the premature infant are accumulating, but the
      results do not suggest a clear-cut advantage for the population at greatest risk
      for death and disability. Whether trial design, dose, duration of therapy, or
      other factors are responsible has not been determined. Further research is needed
      to answer these questions and more clearly define the population of premature
      infants who may derive benefit from this new therapy.

PMID- 17008854
TI  - Organ transplants in children and adolescents: social, emotional and
      psychopathological problems.
AB  - Organ transplantation has become the treatment of choice for a number of life
      threatening childhood illnesses. Our review of the literature on the psychiatric
      aspects of organ transplantation in children and adolescents suggests that
      transplant programs routinely use psychosocial evaluations as a component of
      their assessment and to screen transplant recipients. This study explores 5
      psychiatric issues raised by paediatric transplantation: 1) the role of family;
      2) children's and adolescents' perception of illness; 3) pretransplant evaluation
      of a child's psychological state and environment; 4) the wait; 5) long-term
      effects. We conclude with recommendations for further research and the
      development of standardized assessment designed for the pediatric population.

PMID- 17008855
TI  - Risk factors for suicidal behavior in adolescents.
AB  - Adolescent suicide is today a public health problem among the leading cause of
      mortality among adolescents and young adults. There seems to be many reasons for
      this increase (which has different trends in different populations), but
      associations have been found with increased substance abuse, television and video
      violence, socio-economic status and easy access to firearms. Gender differences
      have also been observed with crime, suicide and substance abuse higher among
      males, while eating disorder, depression and suicidal behavior more prevalent
      among females. This paper will review prevalence and incidence of adolescent
      suicidal behavior, socio-demographic and psychological risk factors, associated
      cognitive factors and socio-economic factors. Risk factors include previous
      suicide attempts, a history of others in the family who have been suicidal,
      mental illness, alcohol and drug use, and other self-destructive behaviors as
      well as consideration being given to hopelessness, hostility, negative self
      concept and isolation. At the individual difference level, factors such as trait
      depression, anger and hostility, perfectionism and social sensitivity would seem
      critical variables, as would age, gender and intellectual functioning.
      Sociological and family-related factors may also be implicated including
      dysfunctional family organizations, a history of physical or psychological abuse
      (sexual abuse) and limited extent of social support networks. A frequently
      reported precipitating event of suicidal behavior is family adversity including
      rejection, separation and interpersonal conflict. At a socio-economic level it
      would seem essential to provide comprehensive document about the social and
      economic conditions from which the adolescent comes.

PMID- 17008856
TI  - Overweight and hypertension: longitudinal study in school-aged children.
AB  - AIM: A continuous increase in overweight has been documented in the paediatric
      population. The increase occurred in many developed and also developing
      countries. In the United States prevalence of overweight is 21.5% among African
      Americans, 21.8% among Hispanics, and 12.3% among non-Hispanic whites; in Europe,
      from 10% to 20% in Northern Europe and 20% to as high as 36% in parts of Southern
      Italy (International Obesity Task Force data). The association between overweight
      and hypertension in children has been reported. This longitudinal study assessed
      the prevalence of hypertension and the relationships between gender, overweight,
      and blood pressure. METHODS: School-based screening was performed in 1.563
      children (3-16 years). Age, gender, height, weight and blood pressure were
      registered every year for 3 subsequent years, in the period 1997-2000. Body mass
      index (BMI, kg/m2) was calculated and overweight was defined as centile
      corresponding to BMI = or >25 at 18 years. Blood pressure > 95th centile defined
      hypertension. RESULTS: The prevalence of elevated blood pressure at first, second
      and third screenings was 35.1%, 33.8% and 23.9% in males, and 41%, 40.2% and
      31.2% in females. The relative risk was significant for overweight subjects.
      CONCLUSIONS: These results confirm an increasing epidemic of cardiovascular risk
      in children, as evidenced by an increase in the prevalence of overweight and
      hypertension. This increase in association with other cardiovascular risk factors
      that include dyslipidemia, insulin resistance, glucose intolerance, type II
      diabetes mellitus, suggest the necessity of accurate prevention strategies.

PMID- 17008857
TI  - Hormonal, auxological and clinical follow-up in children with connatal HIV
      infection. Personal records.
AB  - AIM: HIV infection and antiretroviral drugs have relevant endocrine implications,
      affecting growth and pubertal development. Moreover stature impairment cannot
      depend only on decreased hormonal secretion. METHODS: We studied for 7 years
      growth, puberty, bone maturation, hormonal secretion [Growth Hormone (GH) basal
      and after stimulation with Clonidin and Insulin, Insulin-like Growth Factor 1
      (IGF-1), Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), FSH, LH- gonadic
      hormones axis, ACTH, Cortisol, TSH, fT4, T4, T3, anti-thyroid antibodies, Leptin]
      of 10 HIV-infected children. RESULTS: In 3 patients stature was <-2 SDS in the
      first 2 years and in prepubertal age, with intervals of improved growth. The
      weight was >2 SDS in 6 children, <-2 SDS in 1 girl, while the other 3 patients
      had a weight <-2SDS only in the first 2 years of life. Height growth velocity was
      >10 degrees Centile all over the years of follow-up in 9 patients, while weight
      growth velocity was pathological in 5. Leptinemia showed higher levels at the
      beginning of follow up: 0.82-11.68 ng/L (M+/-DS: 3.29+/-4.15) than at the end of
      the study: 0.2-3 ng/L (M+/-DS: 1.65+/-1.01). Leptin levels showed a statistically
      significant correlation with CD4/CD8 count (P: 0.010; r: 0.916) and with the CDC
      stage (P: 0.006; r: 0.937), meaning a strong link to the severity of the disease.
      CONCLUSIONS: A good clinical control of HIV infection can guarantee growth within
      physiological centile in most of HIV-infected children. Over all IGFBP-3 and IGF
      1 are good markers of growth, more usable than GH.

PMID- 17008858
TI  - Treatment for acute lymphoblastic leukemia in children is associated with
      papillary carcinoma of thyroid, but not with thyroid disfunction.
AB  - AIM: The treatment of acute lymphoblastic leukemia (ALL) in children may cause
      sequelae, some appearing only at long-term follow-up. We investigated the thyroid
      gland morphology and the function of the pituitary-thyroid axis in a group of
      patients treated for ALL in childhood. METHODS: A cohort study was conducted at a
      tertiary medical center. Thirty-three children (22 males and 11 females; age:
      11.9+/-3 years; range: 6 to 18 years) were studied. The mean age at the time of
      chemotherapy and prophylactic cranial irradiation (12-24 Gy) was 5.5+/-2.6 years
      (range: 1 to 14 years). The average length of the follow-up was 6.1+/-3 years
      (range: 2 to 12 years). Thyroid morphology (n=33) was evaluated by palpation and
      ultrasonography. Thyroid function (n=30) was evaluated measuring total T3 and T4,
      and by the thyrotrophin-releasing hormone (TRH) test. Prolactin secretion was
      assessed before and after injection of TRH to evaluate the diagnostic test
      accuracy. RESULTS: One out of the 33 children (3%) was found to have a papillary
      carcinoma of thyroid four years after ALL treatment. Thyroid function was normal
      in all the patients, however one case (3%) showed high TSH (9.2 microU/mL) and
      prolactin (37.5 ng/mL) basal levels, but normal responses to TRH (TSH = 17.8
      microU/mL; prolactin = 82.3 ng/mL). These hormonal alteration were not confirmed
      at follow-up: TSH = 1.6 microU/mL and prolactin = 13.7 ng/mL. CONCLUSIONS: In
      this cohort of patients, the treatment of ALL was associated with one case of
      thyroid carcinoma, but it did not produce adverse effect on the thyroid function,
      at least after a follow-up lasted on average 6 years.

PMID- 17008859
TI  - [Incidence of nosocomial rotavirus infections in a pediatric hospital over a 3
      year period].
AB  - AIM: To estimate the incidence rate of hospital-acquired rotavirus infections
      (HRI) in a paediatric hospital in a 3-year period; the risk of HRI associated to
      age, sex, ward, season; the cost determined by HRI for the healthcare system.
      METHODS: Retrospective epidemiological study, carried out using hospital
      datasets, with the analysis of some clinical records. RESULTS: In the 2003-2005
      period the HRI incidence rate was 1.9% (mean age 15.2 months, SD 11.8, range 1.5
      49), with a decreasing trend over years. Children aged less than 8 months were at
      higher risk of HRI than others (RR 1.83, CI 95% 1.18-2.85) as well as were
      children admitted to a 0-18 months pediatric medicine ward (RR=2.84, CI 95% 1.78
      4.5) and to an infectious diseases ward (RR=4.9, CI 95% 3.4-7). The incidence of
      HRI was higher in the winter than in the rest of the year (RR 1.59, CI 95% 1.07
      2.36). The hospital stay of children with HRI was prolonged by a mean of 5.2 days
      compared to age, sex and comorbidity-matched controls. (P=0.02). CONCLUSIONS: The
      method used in this study is easily reproducible. Data obtained can be used as
      internal quality indicators and to evaluate the performance of different hospital
      wards in infection control. Infection prevention activities should involve
      mothers and families of hospitalized children, as they perform on them a great
      deal of basic care and hygiene activities which are at risk for hospital cross
      infections.

PMID- 17008860
TI  - Pediatric highly active antiretroviral therapy in Mozambique: an integrated model
      of care.
AB  - AIM: To test the impact of a public health model to implement HIV pediatric care
      in Limited Resource Settings. METHODS: A retrospective study on the clinical
      files of 679 Mozambican children (mean age 4.4 years; SD 3.2), has been carried
      out. The pediatric patients received HAART (Highly Active Anti-Retroviral
      Therapy) in the framework of DREAM, a nationwide public health program offering
      an integrated model of care to HIV patients including free-of-charge HAART and
      monitoring, nutritional assessment and supplementation, peer-to-peer education,
      active tracing of the dropped out patients. RESULTS: HAART was started in 297
      subjects out of 679. The median time of treatment was 286 (IQ 25-75:125-465).
      Mortality rate was lower in the sub-sample receiving HAART (8.4%; CI 95%: 5.2
      11.6 vs 13.1%; CI 95%: 9.7-16.5). After 6 months of treatment the percentage of
      viral load lower than 400 copies/mL rose from 4.9% to 46.3%. The percentage of
      patients with less than 15% of CD4 cells out of the total lymphocyte count and
      the percentage of patients below the 2 z-score decreased from 56.4% and 58.1% to
      8.8% and 38.1% respectively. CONCLUSIONS: Pediatric HAART in limited resource
      settings often face difficulties to handle complex treatment schemes, but the
      implemented model seems to be an effective tool to reduce mortality rate in HIV
      positive pediatric population.

PMID- 17008861
TI  - Weaning of epoprostenol in a small infant receiving concomitant bosentan for
      severe pulmonary arterial hypertension secondary to bronchopulmonary dysplasia.
AB  - Endothelin receptor antagonism is an important therapeutic tool of pulmonary
      arterial hypertension (PAH). Bosentan was the first orally active, dual
      antagonist of endothelin receptors in human adults, and has been recently
      considered for children as well. However, little is known about bosentan
      treatment in children weighing less than 10 kg. We describe the use of bosentan
      concomitantly to epoprostenol in an infant weighing 3.5 kg and affected with
      severe bronchopulmonary dysplasia (BPD) and PAH. At 5 months old, when she
      presented subsystemic PAH secondary to severe BPD, she was treated with oxygen,
      digoxin and diuretics. At 8 months old, due to severe PAH not responsive to 100%
      oxygen, high frequency oscillatory ventilation (HFOV) and nitric oxide (NO), we
      started epoprostenol and bosentan. Bosentan dose was doubled at 9 months old,
      when HFOV and NO were slowly discontinued due to improved oxygenation index.
      Regular echocardiographic measurements of systolic right ventricular pressure
      were recorded by the method of tricuspidal atrio-ventricular gradient. A four
      month combined epoprostenol and bosentan treatment decreased systolic right
      ventricular pressure from 68% to 40% of the systemic level, till its
      normalization at 11 months old. Later, when bosentan and epoprostenol were
      discontinued and sildenafil was started, severe PAH was reported again. Our
      patient died due to septic shock and refractory hypoxia at 14 months old.

PMID- 17008862
TI  - Small bowel intussusception by local recurrence of an inflammatory
      myofibroblastic tumor: report of a case and review of the literature.
AB  - Inflammatory myofibroblastic tumor (IMT) of the ileum is a rare, usually solitary
      lesion, that frequently presents small-intestinal intussusception and
      obstruction. We describe an IMT of the ileum in a 4.5-year old child who
      presented a small bowel intussusception. During laparotomy, an annular mass
      around the ileum was resected, and the IMT was histologically diagnosed. Three
      months after the operation, the patients were hospitalized with the symptoms of
      intestinal obstruction. Laparotomy showed a ileal intussusception. Along the
      previous suture line of anastomosis, a smooth polypoid tumor was evident.
      Segmental resection of the ileum, including the tumor mass, was performed. The
      IMT was immunohistochemically diagnosed. The patient was asymptomatic at 3 year
      follow-up. A review of the literature for this rare entity emphasizes the
      importance of immunohistochemical confirmation of its benign nature. Because of
      the risk of local recurrence, IMT cases should have a long-term follow-up.

PMID- 17008863
TI  - Benign paroxysmal torticollis of infancy. A case report.
AB  - Benign paroxysmal torticollis of infancy is a benign, rare, probably under
      recognised disorder, characterized by recurrent episodes of head tilting. The
      diagnosis is primarily one of pattern recognition and exclusion of alternatives
      conditions; other symptoms, such as vomiting, pallor and eyes' rotation, may be
      associated with or rapidly follow the attack, leading to misdiagnosis of this
      disease. The exact pathogenesis of benign paroxysmal torticollis is not clear,
      but a close relationship with childhood periodic syndromes is supposed. Due to
      the difficulty in defining the disease, this event has implications with respect
      to the training and education of practice providers and emergency physicians. We
      describe the case of a 7-month-old infant with benign paroxysmal torticollis
      recently observed, discuss the clinical presentation and review the literature.

PMID- 17008864
TI  - [Who was the very first teacher of paediatrics in Italy?].
AB  - It has always been said that the first teachings of paediatrics in Italy were
      those of Dante Cervesato in Padua. However, documents indicate the historic
      groundlessness of such information. During the period after the unification of
      Italy and before Cervesato, teaching was carried out in Venice, Siena, Naples and
      Genoa. The first teaching post with a teaching hospital was founded in 1882 and
      appointed to Moise Raffael Levi as a temporary professor following a national
      exam in Florence. Cervesato began lessons in May 1882, nevertheless was put in
      charge without a ward which was only assigned to him in 1889. He became temporary
      professor in 1885, 13 years after Levi. One cannot conclude without mentioning
      Aurelio Bianchi, Professor Levi's assistant, who had to abandon his university
      career in order to become head of the "Meyer" hospital in Florence due to the
      death of his predecessor.

PMID- 17008865
TI  - Sports-related injuries among high school athletes--United States, 2005-06 school
      year.
AB  - Participation in high school sports helps promote a physically active lifestyle.
      High school sports participation has grown from an estimated 4 million
      participants during the 1971-72 school year to an estimated 7.2 million in 2005
      06. However, despite the documented health benefits of increased physical
      activity (e.g., weight management, improved self-esteem, and increased strength,
      endurance, and flexibility), those who participate in athletics are at risk for
      sports-related injuries. High school athletes account for an estimated 2 million
      injuries, 500,000 doctor visits, and 30,000 hospitalizations annually. To date,
      the study of these injuries has been limited by inabilities to calculate injury
      rates, compare results among groups, and generalize findings from small,
      nonrepresentative samples. During the 2005-06 school year, researchers at a
      children's hospital in Ohio used an Internet-based data-collection tool to pilot
      an injury surveillance system among athletes from a representative national
      sample of U.S. high schools. This report summarizes the findings of that study,
      which indicated that participation in high school sports resulted in an estimated
      1.4 million injuries at a rate of 2.4 injuries per 1,000 athlete exposures (i.e.,
      practices or competitions). Surveillance of exposure-based injury rates in a
      nationally representative sample of high school athletes and analysis of injury
      patterns can help guide activities aimed at reducing these injuries.

PMID- 17008866
TI  - Chikungunya fever diagnosed among international travelers--United States, 2005
      2006.
AB  - Chikungunya virus (CHIKV) is an alphavirus indigenous to tropical Africa and
      Asia, where it is transmitted to humans by the bite of infected mosquitoes,
      usually of the genus Aedes. Chikungunya (CHIK) fever, the disease caused by
      CHIKV, was first recognized in epidemic form in East Africa during 1952-1953. The
      word "chikungunya" is thought to derive from description in local dialect of the
      contorted posture of patients afflicted with the severe joint pain associated
      with this disease. Because CHIK fever epidemics are sustained by human-mosquito
      human transmission, the epidemic cycle is similar to those of dengue and urban
      yellow fever. Large outbreaks of CHIK fever have been reported recently on
      several islands in the Indian Ocean and in India. In 2006, CHIK fever cases also
      have been reported in travelers returning from known outbreak areas to Europe,
      Canada, the Caribbean (Martinique), and South America (French Guyana). During
      2005-2006, 12 cases of CHIK fever were diagnosed serologically and virologically
      at CDC in travelers who arrived in the United States from areas known to be
      epidemic or endemic for CHIK fever. This report describes four of these cases and
      provides guidance to health-care providers. Clinicians should be alert for
      additional cases among travelers, and public health officials should be alert to
      evidence of local transmission of chikungunya virus (CHIKV), introduced through
      infection of local mosquitoes by a person with viremia.

PMID- 17008867
TI  - Importance of culture confirmation of shiga toxin-producing Escherichia coli
      infection as illustrated by outbreaks of gastroenteritis--New York and North
      Carolina, 2005.
AB  - Escherichia coli O157:H7 and other strains of E. coli that produce Shiga toxin
      are collectively known as Shiga toxin-producing E. coli (STEC). The current
      outbreak of STEC O157 infections associated with eating fresh spinach illustrates
      the importance of obtaining isolates to identify the source of the infections.
      Laboratory methods that do not require bacterial culture of stool specimens to
      identify STEC are being used increasingly by clinical diagnostic laboratories,
      sometimes without subsequent confirmation of a strain by isolating it in culture.
      This report describes findings from outbreaks of gastroenteritis in 2005 in New
      York and North Carolina in which clinical diagnostic laboratories initially used
      only non-culture methods to detect Shiga toxin (Stx). The findings highlight the
      importance of confirmation of Stx-positive stool specimens by bacterial culture
      for timely and reliable identification of STEC infections, including E. coli O157
      and non-O157 STEC, to enable implementation of appropriate public health actions.
      An important part of that identification is determining the serotype of all STEC
      isolates and the subtype of STEC O157 strains so that outbreaks can be detected
      and traced back to sources.

PMID- 17008868
TI  - Ongoing multistate outbreak of Escherichia coli serotype O157:H7 infections
      associated with consumption of fresh spinach--United States, September 2006.
AB  - On September 13, 2006, CDC officials were alerted by epidemiologists in Wisconsin
      and Oregon that fresh spinach was the suspected source of small clusters of
      Escherichia coli serotype O157:H7 infections in those states. On the same day,
      New Mexico epidemiologists contacted Wisconsin and Oregon epidemiologists about a
      cluster of E. coli O157:H7 infections in New Mexico associated with fresh spinach
      consumption. Wisconsin public health officials had first reported a cluster of E.
      coli O157:H7 infections to CDC on September 8. On September 12, CDC PulseNet had
      confirmed that the E. coli O157:H7 strains from infected patients in Wisconsin
      had matching pulsed-field gel electrophoresis (PFGE) patterns and identified the
      same pattern in patient isolates from other states. This report describes the
      joint investigation and outbreak-control measures undertaken by state public
      health officials, CDC, and the Food and Drug Administration (FDA). This
      investigation and additional case finding are ongoing.

PMID- 17008869
TI  - Increased risk of malignancies in a population-based study of 818 soft-tissue
      sarcoma patients.
AB  - Soft-tissue sarcomas (STS) have been associated with various rare cancer
      syndromes and occur at increased frequencies in survivors of childhood cancer.
      Also adult patients with STS have been suggested to be at an increased risk of
      additional malignancies. After exclusion of syndrome-associated and radiation
      induced sarcomas, we studied multiple primary malignancies in a population-based
      cohort of 818 patients with primary STS of the extremities and the trunk wall. In
      total, 203 other malignancies developed in 164 (20%) patients median 10 (0-32)
      years before and median 4 (0-35) years after the sarcoma diagnosis. Standardised
      morbidity ratios (SMRs) were determined for primary malignancies following a STS.
      Hereby individuals who had developed a STS were identified to be at increased
      risk of second primary malignancies (SMR for all malignant tumours=1.3; 95%
      CI=1.0-1.5; P=0.02) with STS being the only specific tumour type that occurred at
      an increased risk (SMR=17.6; 95% CI=8.1-33.5; P<0.001). Hence, this population
      based series demonstrates a high frequency of second primary tumours among STS
      patients and indicates a particularly increased risk of developing a new STS.

PMID- 17008870
TI  - Clinicopathological significance of homeoprotein Six1 in hepatocellular
      carcinoma.
AB  - Tumour recurrence and metastases of hepatocellular carcinoma (HCC) after
      hepatectomy are the major obstacles of long-term survival. The present study
      investigated the clinicopathological significance of a possible metastasis
      regulator Six1 in HCC patients who were undergone hepatectomy. Seventy-two pairs
      of RNA and 103 pairs of protein from tumour and adjacent nontumour liver tissues
      of HCC patients were examined. About 85 and 60% of HCC tumour tissues were found
      to overexpress Six1 mRNA and protein, respectively, compared with nontumour liver
      tissues. No Six1 protein was detected in HCC nontumour liver tissues and normal
      liver tissues. Increased Six1 protein expression in HCC patients was
      significantly correlated with pathologic tumour-node-metastasis (pTNM) stage
      (P=0.002), venous infiltration (P=0.004) and poor overall survival (P=0.0423). We
      concluded that Six1 is frequently overexpressed in HCC patients and elevated Six1
      protein in HCC patients may be an indication of advanced stage and poor overall
      survival after hepatectomy.

PMID- 17008871
TI  - Langerhans cells release prostaglandin D2 in response to nicotinic acid.
AB  - Nicotinic acid, used for atherosclerosis treatment, has an adverse effect of skin
      flushing. The flushing mechanism, thought to be caused by the release of
      prostaglandin D(2) (PGD(2)), is not well understood. We aimed to identify which
      cells mediate the flushing effect. Nicotinic acid receptor (GPR109A) gene
      expression was assessed in various tissues and cell lines. Cells expressing
      GPR109A mRNA were further assayed for PGD(2) release in response to nicotinic
      acid. Of all samples, only skin was able to release PGD(2) upon stimulation with
      nicotinic acid. The responsive cells were localized to the epidermis, and
      immunocytochemical studies revealed the presence of GPR109A on epidermal
      Langerhans cells. CD34+ cells isolated from human blood and differentiated into
      Langerhans cells (hLC-L) also showed GPR109A expression. IFNgamma treatment
      increased both mRNA and plasma membrane expression of GPR109A. IFNgamma
      stimulated hLC-Ls released PGD(2) in response to nicotinic acid in a dose
      dependant manner (effector concentration for half-maximum response=1.2 mM+/-0.7).
      Acifran, a structurally distinct GPR109A ligand, also increased PGD(2) release,
      whereas isonicotinic acid, a nicotinic acid analog with low affinity for GPR109A,
      had no effect. These results suggest that nicotinic acid mediates its flushing
      side effect by interacting with GPR109A on skin Langerhans cells, resulting in
      release of PGD(2).

PMID- 17008872
TI  - Electrophilic chemicals but not UV irradiation or reactive oxygen species
      activate Nrf2 in keratinocytes in vitro and in vivo.
AB  - The NF-E2-related factor 2 (Nrf2) transcription factor is a potent inducer of
      cytoprotective genes, which encode--among others--enzymes that detoxify reactive
      oxygen species (ROS). As we demonstrated a crucial role of Nrf2 in the prevention
      of skin carcinogenesis, it is of interest to identify Nrf2-activating factors in
      keratinocytes. For this purpose, keratinocytes from mice transgenic for an Nrf2
      responsive reporter gene were analyzed. Electrophilic compounds activated the
      reporter in keratinocytes, and induced nuclear translocation of Nrf2 and the
      expression of known Nrf2 target genes. This is biologically relevant, as we show
      that Nrf2-mediated gene expression protects keratinocytes from the toxicity of
      these substances. By contrast, hydrogen peroxide, glucose oxidase, UVA, and UVB
      irradiation had no effect, although these treatments strongly increased the
      levels of intracellular ROS. To verify these results in vivo, transgenic reporter
      mice with and without functional Nrf2 alleles were topically treated with
      electrophilic chemicals or irradiated with UVB. Electrophiles but not UVB
      activated the reporter in an Nrf2-dependent manner. These results provide the
      basis for the identification of novel Nrf2 activators in keratinocytes with
      therapeutic potential for skin tumor prevention.

PMID- 17008873
TI  - Reduction of skin barrier function by proteolytic activity of a recombinant house
      dust mite major allergen Der f 1.

PMID- 17008874
TI  - Investigation of mechanisms underlying the T-cell response to the hapten 2,4
      dinitrochlorobenzene.
AB  - T-cell mediated contact sensitization by small molecular weight xenobiotics
      results in significant morbidity and absences from work. To be recognized by T
      cells, xenobiotics must act as haptens, becoming protein-bound. At present, the
      requirement for processing and presentation of xenobiotics, the nature of the T
      cell responses to them and the mechanisms that confer individual susceptibility
      in humans are unclear. We have investigated the T-cell response to the hapten 2,4
      dinitrochlorobenzene (DNCB) which can sensitize all immunocompetent people.
      Fourteen healthy adults were sensitized with DNCB; 11 demonstrated positive T
      cell responses to the chemical in vitro. Responding cells were of both CD4+ and
      CD8+ subsets, of Th1 and Tc1 phenotypes, producing high levels of IFN-gamma and
      low levels of IL-10. DNCB-specific T-cell clones were raised from 2 subjects,
      which in the presence of fixed and unfixed autologous Epstein-Barr virus
      transformed B cells as antigen-presenting-cells (APC), demonstrated that the
      chemical requires metabolic processing by the APC in order to initiate the T-cell
      response. Intracellular-reduced glutathione is consumed in detoxication of DNCB,
      leaving residual non-detoxified DNCB free to bind to proteins. The results
      suggest that DNCB forms multiple haptens with intracellular and extracellular
      proteins leading to Th1 and Tc1 responses in individuals exposed to this
      compound.

PMID- 17008875
TI  - Two common loss-of-function mutations within the filaggrin gene predispose for
      early onset of atopic dermatitis.

PMID- 17008876
TI  - Differences in imiquimod treatment outcome in two patients with bowenoid
      papulosis containing either episomal or integrated human papillomavirus 16.

PMID- 17008877
TI  - Short-term alternating temperature enhances histamine-induced itch: a biphasic
      stimulus model.
AB  - Itch is the major symptom of many allergic or inflammatory skin diseases; yet it
      is still difficult to measure objectively. Human studies on the physiology and
      pathophysiology of the itch sensation (e.g. functional magnetic resonance imaging
      studies) have been hampered by the lack of an efferent and manageable "on-off"
      stimulus. Here, a short-term temperature-modulated human histamine itch model is
      presented. In nine healthy right-handed male volunteers (age 29+/-2.6 years), 1%
      histamine dihydrochloride was used in the skin prick model as standard itch
      stimulus on the right forearm with subsequent thermal modulation of the target
      skin area using a Medoc TSA II NeuroSensory Analyzer thermode. Modulation
      occurred in rapid alternating order from 32 degrees C (neutral) to 25 degrees C
      (slight cold) and vice versa; each temperature block lasted 20 seconds.
      Subjective itch ratings were recorded using a computerized visual analog scale
      (VAS) and - for qualitative assessment - the Eppendorf Itch Questionnaire (EIQ).
      All subjects reported localized itch sensations without pain; mean VAS itch
      intensity was 50.6+/-3.5% during the 25 degrees C blocks and 33.8+/-3.9% during
      the 32 degrees C blocks (P<0.0001). Also, mean EIQ ratings were significantly
      higher related to the 25 degrees C blocks. In spite of the common knowledge that
      intensive cold can inhibit itch sensation, a reproducible, significant
      enhancement of histamine-induced itch by short-term moderate temperature decrease
      could be shown. This effect might be explained by peripheral and central
      adaptation processes triggered by alternating afferent activity patterns and
      might be used - owing to its "on/off" characteristics-in future itch physiology
      studies such as functional magnetic resonance imaging.

PMID- 17008878
TI  - Intermedin: a skin peptide that is downregulated in atopic dermatitis.
AB  - Intermedin (IMD), also called adrenomedullin-2, is a peptide that belongs to the
      calcitonin/calcitonin gene-related peptide/amylin peptide family. IMD exerts many
      effects on the cardiovascular system, gastrointestinal tract, and central nervous
      system. Here, we analyzed the expression of the IMD peptide in human skin of
      healthy controls, in biopsies from lesional and non-lesional areas of atopic
      dermatitis (AD) skin, in cultured human keratinocytes, and in the HaCaT
      keratinocyte cell line at the transcriptional (quantitative reverse transcription
      PCR) and translational (immunohistochemistry) level. IMD messenger RNA (mRNA) and
      protein could be detected in keratinocytes and human skin. Keratinocytes, nerve
      fibers, periglandular cells, arterial/arteriolar smooth muscle cells, and
      pericytes of dermal microvessels were intensely IMD-immunoreactive. The IMD mRNA
      was, compared to healthy skin, significantly reduced in lesional and non-lesional
      areas of AD skin. This was accompanied by a reduction of IMD immunoreactivity in
      pericytes of the upper dermis indicating that skin from AD patients is generally
      affected, and downregulation of IMD in AD skin is not a secondary phenomenon
      caused by acute inflammation but is a general characteristic of AD skin. These
      data further point to a role of IMD expressed by pericytes in conferring higher
      susceptibility of the skin of AD patients to inflammatory stimuli.

PMID- 17008879
TI  - Colocalization of glial fibrillary acidic protein, metallothionein, and MHC II in
      human, rat, NOD/SCID, and nude mouse skin keratinocytes and fibroblasts.
AB  - The expression of glial fibrillary acidic protein (GFAP) by perivascular cells of
      many mammalian organs suggests an as yet unknown function of this intermediate
      filament protein in the maintenance of homeostasis and vascular permeability at
      the blood-tissue interface. Although a similar situation may exist at the air
      tissue interface, the cellular distribution of GFAP in skin tissue has never been
      demonstrated. To approach this issue, we have employed immunofluorescence and
      Western blotting techniques to detect GFAP in skin sections of young and adult
      humans, normal rodents, and two types of mutant mice, as well as in rat lung
      sections, and in cultured human keratinocytes and fibroblasts. Colocalization
      with antigens known to be associated with GFAP in other tissues was also tested.
      Epidermal and hair follicle keratinocytes and dermal fibroblasts showed distinct
      staining for GFAP as well as colocalization with alpha-actin, metallothionein,
      and antigens of the class-II major histocompatibility complex (MHC II). GFAP was
      also identified in rat alveolar fibroblasts which, in common with keratinocytes,
      form part of the air-tissue interface. GFAP was upregulated together with MHC II
      in nude mice but was barely detectable in the skin of non-obese diabetic severe
      combined immunodeficiency mice, suggesting a possible involvement in antigen
      presenting functions. The intriguing distribution of a common set of antigens
      both in certain cells of the integumentary system and at the blood-tissue
      interfaces of internal organs suggests the involvement of these proteins in
      universal mechanisms controlling tissue homeostasis and protection.

PMID- 17008880
TI  - Regulation of UVB-induced IL-8 and MCP-1 production in skin keratinocytes by
      increasing vitamin C uptake via the redistribution of SVCT-1 from the cytosol to
      the membrane.
AB  - It is well known that UVB (290-320 nm) induces inflammation in skin by the
      transcription and release of cytokines and chemokines from skin keratinocytes. In
      addition, it is considered that intracellular reactive oxygen species (ROS) plays
      an important role in UVB-induced inflammatory response in the skin. Therefore, we
      investigated the effect of vitamin C, a potent antioxidant, on the regulation of
      UVB-induced skin inflammation via the modulation of chemokines production.
      Vitamin C uptake into keratinocytes is increased by UVB irradiation in a time-
      and dose-dependent manner through the translocation of sodium-dependent vitamin C
      transporter-1 (SVCT-1), a vitamin C-specific transporter, from the cytosol to the
      membrane. To evaluate the effect of vitamin C on the chemokine mRNA expression,
      we performed RNase protection assay. As a result, there was a remarkable change
      in chemokine mRNA expression, especially IL-8 and monocyte chemoattractant
      protein (MCP)-1 expression. In addition, increased IL-8 and MCP-1 mRNA
      expressions were suppressed by vitamin C treatment. We also confirmed the results
      of protein levels measured by ELISA. Taken together, vitamin C uptake is
      increased in UVB-irradiated keratinocytes through the translocation of SVCT-1 and
      regulates inflammatory response in the skin via the downregulation of IL-8 and
      MCP-1 production.

PMID- 17008881
TI  - Site of blood vessel damage and relevance of CD18 in a murine model of immune
      complex-mediated vasculitis.
AB  - How neutrophils (polymorphonuclear neutrophils, PMNs) damage vessels in
      leukocytoclastic vasculitis (LcV) mediated by immune complexes (ICs) is unclear.
      If degradative enzymes and oxygen radicals are released from PMNs while adhering
      to the inner side of the vessel wall, they could be washed away by the blood
      stream or neutralized by serum protease inhibitors. We investigated if in LcV
      PMNs could damage vessels from the tissue side after transmigration. We used CD18
      deficient (CD18-/-) mice because the absence of CD18 excludes transmigration of
      PMNs. When eliciting the Arthus reaction in ears of CD18-/- mice, deposition of
      ICs was not sufficient to recruit PMNs or to induce IC-mediated LcV. Injection of
      PMNs intradermally in CD18-/- mice allowed us to investigate if bypassing
      diapedesis and placing PMNs exclusively on the abluminal side leads to vascular
      destruction. We found that injected PMNs gathered around perivascular ICs, but
      did not cause vessel damage. Only intravenous injection of wild-type PMNs could
      re-establish the Arthus reaction in CD18-/- mice. Thus, PMNs cause vessel damage
      during diapedesis from the luminal side, but not from the perivascular space. We
      suggest that in order to shield the cytotoxic products from the blood stream, ICs
      induce particularly tight interactions between them, PMNs and endothelial cells.

PMID- 17008882
TI  - Lack of nidogen-1 and -2 prevents basement membrane assembly in skin-organotypic
      coculture.
AB  - Nidogens are considered as classical linkers joining laminin and collagen IV
      networks in basement membranes (BMs); however, recent genetic approaches have
      suggested that nidogens function in a tissue-specific and developmental context.
      Thus, in mice lacking both nidogen-1 and -2 heart and lung were severely
      affected, causing neonatal death. Furthermore, in various locations,
      extravasation of erythrocytes was observed implying microvascular defects. Mice
      expressing solely either isoform, had a functional BM, although nidogen-2 binds
      with lower affinity to the laminin gamma1 chain. Having previously blocked BM
      formation by interfering with nidogen-1 binding to laminin in skin-organotypic
      cocultures, here we investigated the roles of nidogen-1 and -2 in this model. For
      that purpose, human HaCaT cells were grown in three-dimensional cocultures on
      collagen matrices containing murine fibroblasts of varying nidogen deficiency. As
      with our experiments blocking laminin-nidogen interaction, lack of both nidogens
      completely prevented BM deposition and ultrastructural assembly of BM and
      hemidesmosomes, although other BM proteins remained detectable at comparable
      levels with no signs of degradation. Supplementation by recombinant nidogen-1 or 
      2 restored these structures, as shown by immunofluorescence and electron
      microscopy, confirming that in this system nidogen-2 is equivalent to nidogen-1,
      and both can promote the development of a functional BM zone.

PMID- 17008884
TI  - SLURP1 is a late marker of epidermal differentiation and is absent in Mal de
      Meleda.
AB  - SLURP1 is a secreted member of the LY6/PLAUR protein family. Mutations in the
      SLURP1 gene are the cause of Mal de Meleda (MDM), a rare autosomal recessive
      genetic disease, characterized by inflammatory palmoplantar keratoderma. In this
      study, we have analyzed the expression of SLURP1 in normal and MDM skin. SLURP1
      was found to be a marker of late differentiation, predominantly expressed in the
      granular layer of skin, notably the acrosyringium. Moreover, SLURP1 was also
      identified in several biological fluids such as sweat, saliva, tears, and urine
      from normal volunteers. In palmoplantar sections from MDM patients, as well as in
      their sweat, mutant SLURP1, including the new variant R71H-SLURP1, was either
      absent or barely detectable. Transfected human embryonic kidney 293T cells
      expressed the MDM mutant SLURP1 containing the single amino-acid substitution
      G86R but did not tolerate the MDM mutation W15R located in the signal peptide.
      Thus, most MDM mutations in SLURP1 affect either the expression, integrity, or
      stability of the protein, suggesting that a simple immunologic test could be used
      as a rapid screening procedure.

PMID- 17008883
TI  - Surfactant protein expression in human skin: evidence and implications.
AB  - The presence of surfactant proteins (SPs), critical to local barrier and defense
      functions and usually associated with the lung, was revealed in adult and fetal
      human skin complementary deoxyribonucleic acid, in skin samples from three adult
      female donors and also in cultured fibroblasts, keratinocytes, and melanocytes.
      Using reverse transcription-PCR, SP-A, SP-B, SP-C, and SP-D messenger ribonucleic
      acid expression was detected to varying extents in the different skin sources.
      The stronger expression of SP-C in fetal skin, compared to adult skin, suggested
      that the role of this protein alters with age. Immunohistochemical studies showed
      variable distribution of SPs in human epidermis and dermis, confirming that these
      proteins are indeed translated and expressed in skin tissue. In vitro studies
      showed that the surface tension of SP-deficient artificial sebum is (a) lowered
      by skin-extracted SP-B and (b) further reduced to a level comparable to normal
      sebum by the additional presence of skin-extracted SP-A and SP-D, consistent with
      their surface tension-lowering capabilities in lung. The possible roles of SPs in
      skin, based on their known functions in the lung are discussed. However, their
      potential as therapeutic targets or diagnostic markers of skin disease remains to
      be elucidated.

PMID- 17008885
TI  - HLA-C expression pattern is spatially different between psoriasis and eczema skin
      lesions.
AB  - Interactions between genetic and environmental factors underlie the immune
      dysregulation and keratinocyte abnormalities that characterize psoriasis. Among
      known psoriasis susceptibility loci (PSORS), PSORS1 on chromosome 6 has the
      strongest association to disease. Altered expression of some PSORS1 candidate
      genes has been reported but little is known about HLA-C expression in psoriasis.
      This study compared expression of major histocompatibility complex class Ia and
      HLA-C in psoriasis, allergic contact eczema, and normal skin. Although HLA-C was
      abundant in protein extracts from both eczema and psoriasis, a consistent and
      intriguing difference in the expression pattern was observed; strong
      immunoreactivity in the basal cell layer, polarized towards the basement membrane
      in psoriasis, whereas in eczema lesions HLA-C immunostaining was present mostly
      in suprabasal cells. Inflammatory cells in the dermis were strongly stained in
      both diseases. Normal skin epithelium showed less intense but similar HLA-C
      staining as eczema lesions. HLA class Ia expression overall resembled that of HLA
      C in all samples. The distinct HLA-C expression patterns in psoriasis and eczema
      suggest a functional role in the specific psoriasis immune response and not only
      a general feature of inflammation.

PMID- 17008886
TI  - Nicotine and biochanin A, but not cigarette smoke, induce anti-inflammatory
      effects on keratinocytes and endothelial cells in patients with Behcet's disease.
AB  - During periods of smoking, patients with Behcet's disease have less oral aphthae
      than in abstinence. To elucidate this observation, human keratinocytes and dermal
      microvascular endothelial cells (HMEC-1) were incubated with serum of 20 patients
      with Behcet's disease and 20 healthy controls for 4 hours. Maximum non-toxic
      concentrations were determined and the cells were further treated with 6 microM
      nicotine, 3.3% cigarette smoke extract (CES), 100 microM biochanin A, and
      6.25/12.5 microM pyrrolidine dithiocarbamate alone and in combinations for 24
      hours. Serum IL-8 levels of patients were significantly lower than those of
      controls. However, after 4 hours incubation with patients' sera, IL-8 release by
      both cell types was markedly increased when compared with the corresponding serum
      levels. The levels of IL-6 and vascular endothelial growth factor (VEGF) release
      were after 4 hours similar with the corresponding levels in serum. IL-1 was not
      detected. Nicotine significantly decreased IL-8 and -6 release by HMEC-1
      maintained in both patients' and controls' sera, but only IL-6 release by
      keratinocytes maintained in patients' sera. VEGF release by both cells was
      markedly increased after nicotine treatment in either serum. CES significantly
      decreased IL-8 release and increased production of VEGF in keratinocytes
      maintained in patients' serum. The phytoestrogen biochanin A alone and in
      combination with nicotine further decreased the secretion of IL-8, -6, and VEGF
      in all experimental settings. Our data support a specific anti-inflammatory
      effect of nicotine on keratinocytes and endothelial cells maintained in the serum
      of patients with Behcet's disease. Moreover, biochanin A is likely to exhibit
      similar and even more profound results than nicotine.

PMID- 17008888
TI  - Detection of a new JAK2 D620E mutation in addition to V617F in a patient with
      polycythemia vera.

PMID- 17008887
TI  - Glutathione S-transferase (GSTM1, GSTT1 and GSTA1) polymorphisms and outcomes
      after treatment for acute myeloid leukemia: pharmacogenetics in Southwest
      Oncology Group (SWOG) clinical trials.

PMID- 17008889
TI  - Human neutrophil elastase is not a target for therapy in chronic myeloid
      leukaemia.

PMID- 17008890
TI  - Activating mutations in NOTCH1 in acute myeloid leukemia and lineage switch
      leukemias.
AB  - Activating mutations in NOTCH1 are found in over 50% of human T-cell
      lymphoblastic leukemias (T-ALLs). Here, we report the analysis for activating
      NOTCH1 mutations in a large number of acute myeloid leukemia (AML) primary
      samples and cell lines. We found activating mutations in NOTCH1 in a single M0
      primary AML sample, in three (ML1, ML2 and CTV-1) out of 23 AML cell lines and in
      the diagnostic (myeloid) and relapsed (T-lymphoid) clones in a patient with
      lineage switch leukemia. Importantly, the ML1 and ML2 AML cell lines are derived
      from an AML relapse in a patient initially diagnosed with T-ALL. Overall, these
      results demonstrate that activating mutations in NOTCH1 are mostly restricted to
      T-ALL and are rare in AMLs. The presence of NOTCH1 mutations in myeloid and T
      lymphoid clones in lineage switch leukemias establishes the common clonal origin
      of the diagnostic and relapse blast populations and suggests a stem cell origin
      of NOTCH1 mutations during the molecular pathogenesis of these tumors.

PMID- 17008891
TI  - Do RARA/PML fusion gene deletions confer resistance to ATRA-based therapy in
      patients with acute promyelocytic leukemia?

PMID- 17008892
TI  - A novel Bcr-Abl splice isoform is associated with the L248V mutation in CML
      patients with acquired resistance to imatinib.

PMID- 17008898
TI  - USDA revises policies on veterinary care and submission of annual reports.

PMID- 17008899
TI  - Questions for the investigator. IACUC needs more information.

PMID- 17008900
TI  - Questions for the investigator.

PMID- 17008901
TI  - Questions for the investigator. Monitor matters.

PMID- 17008902
TI  - Questions for the investigator. Broader, and more specific.

PMID- 17008903
TI  - Exophthalmos and corneal edema in a young ferret. Diagnosis: glaucoma.

PMID- 17008905
TI  - Blood collection from the cranial vena cava of the ferret.
AB  - The domestic ferret, though not as common a laboratory animal as the rat or
      mouse, serves as a model in critical research areas, including influenza biology
      and vaccine development. Studies involving ferrets necessitate knowledge of
      proper blood collection methods, such as cranial vena cava puncture.

PMID- 17008908
TI  - Dose-dependent effects of chemical immobilization on the heart rate of embryonic
      zebrafish.
AB  - The small size and optical transparency of zebrafish embryos and larvae greatly
      facilitate modern intravital microscopic phenotyping of these experimentally
      tractable laboratory animals. Neither the experimentally derived dose-response
      relationships for chemicals commonly used in the mounting of live fish larvae,
      nor their effect on the stress of the animal, are currently available in the
      research literature. This is particularly problematic for IACUCs attempting to
      maintain the highest ethical standards of animal care in the face of a recent
      spate in investigator-initiated requests to use embryonic zebrafish as
      experimental models. The authors address this issue by describing the dose
      dependent efficacy of several commonly used chemical mounting treatments and
      their effect on one stress parameter, embryo heart rate. The results of this
      study empirically define, for the first time, effective, minimally stressful
      treatments for immobilization and in vivo visualization during early zebrafish
      development.

PMID- 17008909
TI  - Animal reuse: balancing scientific integrity and animal welfare.
AB  - Research scientists and IACUC members are faced with the difficult task of
      balancing the necessity of using animals for experimental research and their
      mandate to protect the welfare of those animals used in that research. One way to
      reduce the number of research animals would be to reuse them, but the regulations
      do not specifically address this topic. To learn more about the reuse of research
      animals, the authors conducted an online survey of animal facilities involved in
      preclinical studies. Their results suggest that animal reuse is a common practice
      in the field.

PMID- 17008910
TI  - Pneumocystis: newer knowledge about the biology of this group of organisms in
      laboratory rats and mice.
AB  - This review is an update on some of the remarkable advances that have led to
      greater understanding of Pneumocystis, an important group of rodent pathogens.
      The author outlines the life cycle of these pulmonic fungi, their taxonomic
      position, and their nomenclature. He discusses how infections begin and spread in
      laboratory rodent colonies, and how those infections are inadvertently maintained
      in barriered breeding colonies. He also addresses the diagnosis of Pneumocystis
      infection and provides suggestions for the establishment of Pneumocystis-free
      animal colonies.

PMID- 17008913
TI  - Broad-spectrum caspase inhibitors: from myth to reality?

PMID- 17008915
TI  - Cavitation of embryoid bodies requires optimal oxidative phosphorylation and AIF.

PMID- 17008914
TI  - Death receptor ligation triggers membrane scrambling between Golgi and
      mitochondria.
AB  - Subcellular organelles such as mitochondria, endoplasmic reticulum (ER) and the
      Golgi complex are involved in the progression of the cell death programme. We
      report here that soon after ligation of Fas (CD95/Apo1) in type II cells,
      elements of the Golgi complex intermix with mitochondria. This mixing follows
      centrifugal dispersal of secretory membranes and reflects a global alteration of
      membrane traffic. Activation of apical caspases is instrumental for promoting the
      dispersal of secretory organelles, since caspase inhibition blocks the outward
      movement of Golgi-related endomembranes and reduces their mixing with
      mitochondria. Caspase inhibition also blocks the FasL-induced secretion of
      intracellular proteases from lysosomal compartments, outlining a novel aspect of
      death receptor signalling via apical caspases. Thus, our work unveils that Fas
      ligand-mediated apoptosis induces scrambling of mitochondrial and secretory
      organelles via a global alteration of membrane traffic that is modulated by
      apical caspases.

PMID- 17008916
TI  - Granzyme K cleaves the nucleosome assembly protein SET to induce single-stranded
      DNA nicks of target cells.
AB  - Although granzymes (Gzms) A- and B-induced cell death pathways have been defined,
      little is known about how other orphan Gzms function in CTL-mediated
      cytotoxicity. GzmK and A are tryptases among all the Gzms of humans and they are
      closely linked on the same chromosome. In this study, we showed that GzmK can be
      efficiently delivered into target cells with a cationic lipid protein
      transfection reagent Pro-Ject. We found human GzmK triggers rapid cell death
      independently of caspase activation. The features of death are characterized by
      rapid externalization of phosphatidylserine, nuclear morphological changes and
      single-stranded DNA nicks. GzmK hydrolyzes the nucleosome assembly protein SET in
      its recombinant and native forms or in intact cells. Cleavage of SET by GzmK
      abrogates its nucleosome assembly activity. After GzmK loading, SET and DNase
      NM23H1 rapidly translocate into the nucleus and SET is cleaved, where the
      nuclease activity of NM23H1 is activated to nick chromosomal DNA.

PMID- 17008917
TI  - XLX is an IAP family member regulated by phosphorylation during meiosis.
AB  - The balance between proliferation and cell death is critical for embryonic
      development and adult tissue homeostasis. Within an individual cell, coordination
      of these pathways is aided by direct communication between cell cycle factors and
      molecules that regulate apoptosis. Here, we show that XLX, a Xenopus laevis
      inhibitor of apoptosis (IAP) family member, exhibits characteristics typical of
      an IAP, such as caspase inhibition and autoubiquitylation. However, unlike other
      IAPs described thus far, we found that XLX is phosphorylated during meiosis by
      protein kinases that belong to the MAPK and MPF pathways. Finally, we show that
      caspase-dependent cleavage of XLX is altered when XLX is phosphorylated. In
      addition to furthering our understanding of the post-translational regulation of
      an IAP, these findings reveal a novel link between cell cycle-regulated protein
      kinases and a component potentially involved in apoptosis.

PMID- 17008918
TI  - Fertile ground.

PMID- 17008919
TI  - What is the value of early endoscopy in upper gastrointestinal bleeding?

PMID- 17008920
TI  - High-dose or low-dose omeprazole after endoscopic hemostasis in patients with
      peptic ulcer bleeding?

PMID- 17008921
TI  - How effective is adalimumab for inducing remission in patients with moderate-to
      severe Crohn's disease?

PMID- 17008922
TI  - A biopsy-avoiding approach to the diagnosis of celiac disease--how accurate is
      the immersion technique?

PMID- 17008923
TI  - Should surveillance for hepatocellular carcinoma be increased in patients with
      cirrhosis and small liver nodules?

PMID- 17008924
TI  - Endoscopic markers for celiac disease.
AB  - Celiac disease is common and can present with nonspecific upper gastrointestinal
      symptoms. Patients may therefore undergo esophagogastroduodenoscopy as their
      initial investigation. Markers of villous atrophy, which can be seen in the
      duodenum during endoscopy, are well described. They have limited sensitivity for
      patients with mild enteropathy and duodenal biopsies should be performed if there
      is strong suspicion of celiac disease irrespective of endoscopic appearance.
      Endoscopic markers do, however, allow the selection of patients with nonspecific
      symptoms for duodenal biopsy, and these markers should, therefore, be looked for
      routinely during esophagogastroduodenoscopy.

PMID- 17008925
TI  - Drug insight: statins and gastrointestinal cancer.
AB  - Statins are popular lipid-lowering drugs that have had a great impact on the
      primary and secondary prevention of cardiovascular diseases. Basic and clinical
      research have also revealed that statins have biologic activities that go beyond
      lipid lowering, and suggest that they might have other therapeutic benefits.
      Perhaps the most exciting of these additional biologic effects is the finding
      that statins can exert an anticancer effect on cultured cancer cells, and in
      animal models. Clinical studies of statins for the treatment and prevention of
      cancer have, however, produced conflicting results. This review critically
      evaluates the current body of literature on the role of statins in the treatment
      and prevention of gastrointestinal cancers, with particular focus on clinical and
      observational studies.

PMID- 17008926
TI  - Primer: managing NSAID-induced ulcer complications--balancing gastrointestinal
      and cardiovascular risks.
AB  - Ulcer complications associated with the use of NSAIDs, in high-risk patients, are
      often caused by a failure to identify patients' risk factors, concomitant use of
      aspirin or multiple NSAIDs, and underutilization of gastroprotective agents.
      Current data suggest that cyclo-oxygenase 2 (COX2) inhibitors and some
      nonselective NSAIDs increase the risk of myocardial infarction. Physicians must,
      therefore, take into account both the gastrointestinal and the cardiovascular
      risks of individual patients when prescribing NSAIDs. In patients with a low
      cardiovascular risk, NSAIDs can be prescribed according to the level of
      gastrointestinal risk. Patients with a moderate gastrointestinal risk (one or two
      risk factors) should receive a COX2 inhibitor or an NSAID plus a PPI or
      misoprostol. Patients with more than two gastrointestinal risk factors or prior
      ulcer complications require the combination of a COX2 inhibitor and a PPI.
      Patients with a high cardiovascular risk (e.g. coronary heart disease or an
      estimated 10-year cardiovascular risk greater than 10%) should receive
      prophylactic aspirin and combination therapy with a PPI or misoprostol
      irrespective of the presence of gastrointestinal risk factors. Naproxen is the
      preferred NSAID because it is not associated with excess cardiovascular risk.
      Patients with a high cardiovascular risk and a very high gastrointestinal risk
      should avoid using NSAIDs or COX2 inhibitors.

PMID- 17008927
TI  - Mechanisms of disease: mechanisms and clinical implications of cholestasis in
      sepsis.
AB  - Cholestasis is a common complication in patients with extrahepatic bacterial
      infection and sepsis. This article gives a comprehensive overview of the
      molecular and cellular mechanisms of sepsis-associated cholestasis. Recent
      advances in the understanding of intrahepatic cholestasis have allowed us to
      delineate the molecular mechanisms that underlie sepsis-associated cholestasis
      and to describe their potential clinical and therapeutic applications. The
      mechanisms and clinical presentation of sepsis-associated liver injury vary
      according to the severity of the bacterial infection. Proinflammatory cytokines
      and nitric oxide cause cholestasis by impairing hepatocellular and ductal bile
      formation. Ischemic liver injury and, rarely, progressive sclerosing cholangitis
      can also be found in patients with septic shock, or major trauma with systemic
      inflammatory response syndrome. Treatment is mainly focused on eradication of the
      underlying infection and managing the sepsis. The use of ursodeoxycholic acid or
      extracorporeal liver support as treatments for sepsis-associated cholestasis is
      under investigation, but neither can be recommended in routine clinical practice
      at present. Patients with progressive sclerosing cholangitis should be considered
      for orthotopic liver transplantation.

PMID- 17008928
TI  - A family history of pancreatic cancer.
AB  - BACKGROUND: A 65-year-old white male with a family history of pancreatic cancer
      and a personal history of two episodes of acute pancreatitis was referred to our
      department in January 2005 by his primary-care physician for an assessment of his
      pancreatic cancer risk. INVESTIGATIONS: Physical exam, laboratory investigations,
      CT scan, endoscopic ultrasonography, endoscopic retrograde
      cholangiopancreatography. DIAGNOSIS: Familial pancreatic cancer. MANAGEMENT:
      Subtotal pancreatectomy, referral to genetic counselor, and continued
      surveillance.

PMID- 17008929
TI  - Asn- and Asp-mediated interactions between transmembrane helices during
      translocon-mediated membrane protein assembly.
AB  - Inter-helix hydrogen bonding involving asparagine (Asn, N), glutamine (Gln, Q),
      aspartic acid (Asp, D) or glutamic acid (Glu, E) can drive efficient di- or
      trimerization of transmembrane helices in detergent micelles and lipid bilayers.
      Likewise, Asn-Asn and Asp-Asp pairs can promote the formation of helical hairpins
      during translocon-mediated membrane protein assembly in the endoplasmic
      reticulum. By in vitro translation of model integral membrane protein constructs
      in the presence of rough microsomes, we show that Asn- or Asp-mediated
      interactions with a neighbouring transmembrane helix can enhance the membrane
      insertion efficiency of a marginally hydrophobic transmembrane segment. Our
      observations suggest that inter-helix hydrogen bonds can form during Sec61
      translocon-assisted insertion and thus could be important for membrane protein
      assembly.

PMID- 17008930
TI  - Alternative editing of cytochrome c oxidase III mRNA in trypanosome mitochondria
      generates protein diversity.
AB  - Trypanosomes use RNA editing to produce most functional mitochondrial messenger
      RNA. Precise insertion and deletion of hundreds of uridines is necessary to make
      full-length cytochrome c oxidase III (COXIII) mRNA. We show that COXIII mRNA can
      be alternatively edited by a mechanism using an alternative guide RNA to make a
      stable mRNA. This alternatively edited mRNA is translated to produce a unique
      protein that fractionates with mitochondrial membranes and colocalizes with
      mitochondrial proteins in situ. Alternative RNA editing represents a previously
      unknown mechanism generating protein diversity and, as such, represents an
      important function for RNA editing.

PMID- 17008932
TI  - Saporin as a novel suicide gene in anticancer gene therapy.
AB  - We used a non-viral gene delivery approach to explore the potential of the plant
      saporin (SAP) gene as an alternative to the currently employed suicide genes in
      cancer therapy. Plasmids expressing cytosolic SAP were generated by placing the
      region encoding the mature plant ribosome-inactivating protein under the control
      of cytomegalovirus (CMV) or simian virus 40 (SV40) promoters. Their ability to
      inhibit protein synthesis was first tested in cultured tumor cells co-transfected
      with a luciferase reporter gene. In particular, SAP expression driven by CMV
      promoter (pCI-SAP) demonstrated that only 10 ng of plasmid per 1.6 x 10(4) B16
      cells drastically reduced luciferase activity to 18% of that in control cells.
      Direct intratumoral injection of pCI-SAP complexed with either lipofectamine or N
      (2,3-dioleoyloxy-1-propyl) trimethylammonium methyl sulfate (DOTAP) in B16
      melanoma-bearing mice resulted in a noteworthy attenuation of tumor growth. This
      antitumor effect was increased in mice that received repeated intratumoral
      injections. A SAP catalytic inactive mutant (SAP-KQ) failed to exert any
      antitumor effect demonstrating that this was specifically owing to the SAP N
      glycosidase activity. Our overall data strongly suggest that the gene encoding
      SAP, owing to its rapid and effective action and its independence from the
      proliferative state of target cells might become a suitable candidate suicide
      gene for oncologic applications.

PMID- 17008931
TI  - Live imaging of neural structure and function by fibred fluorescence microscopy.
AB  - Only a few methods permit researchers to study selected regions of the central
      and peripheral nervous systems with a spatial and time resolution sufficient to
      image the function of neural structures. Usually, these methods cannot analyse
      deep-brain regions and a high-resolution method, which could repeatedly probe
      dynamic processes in any region of the central and peripheral nervous systems, is
      much needed. Here, we show that fibred fluorescence microscopy-which uses a small
      diameter fibre-optic probe to provide real-time images-has the spatial resolution
      to image various neural structures in the living animal, the consistency needed
      for a sequential, quantitative evaluation of axonal degeneration/regeneration of
      a peripheral nerve, and the sensitivity to detect calcium transients on a sub
      second timescale. These unique features should prove useful in many physiological
      studies requiring the in situ functional imaging of tissues in a living animal.

PMID- 17008933
TI  - Potent antitumor efficacy of XAF1 delivered by conditionally replicative
      adenovirus vector via caspase-independent apoptosis.
AB  - XAF1 is a newly identified tumor-suppressor gene that can antagonize XIAP and
      sensitize cells to other cell death triggers. In this study, we utilized ZD55, a
      conditionally replicative adenovirus (CRAd) similar to ONYX-015 as the vector to
      transfer XAF1 into the tumor cells to evaluate its antitumor efficacy in vitro
      and in vivo. Potent and specific cytopathic effect (CPE) was observed upon
      infection with ZD55-XAF1 in tumor cell lines. Importantly, ZD55-XAF1 exhibited a
      superior suppression of tumor growth in an animal model of colorectal carcinoma
      in nude mice compared with Ad-XAF1 (E1-deleted replication-defective viral) and
      ONYX-015. Complete eradication of the established tumors was observed in four of
      eight mice. Our data also showed that infection with ZD55-XAF1 resulted in
      caspase-independent apoptosis. Although caspase-3, poly(ADP-ribose) polymerase
      were mildly activated in response to ZD55-XAF1 infection, pretreatment with pan
      caspase inhibitor hardly influence its apoptosis-inducing activity. In summary,
      our study strongly suggested that ZD55-XAF1 could serve as an effective gene
      virotherapy strategy and has highly potential against human cancers.

PMID- 17008935
TI  - The modern surgical management of atrial fibrillation.
AB  - Atrial fibrillation is the most common arrhythmia disorder. Its incidence is
      especially high among patients with valvular heart disease. Patients with atrial
      fibrillation are at a six-fold increased risk of stroke and a two-fold increased
      risk of mortality. Medical management for rhythm control of patients with atrial
      fibrillation is suboptimal and no better than simple rate management. However,
      catheter-based therapies are undergoing intense development. The surgical
      management of atrial fibrillation has undergone considerable innovation in the
      last two decades; it is the subject of this review. The "cut-and-sew" Cox-maze
      III is considered the standard for surgical therapy for atrial fibrillation. More
      recently, several modifications of the Cox maze lesion set and the development of
      alternative energy sources to achieve transmural atrial lesions have led to a
      more simplified maze procedure. This simplified left-sided maze procedure has
      demonstrated excellent efficacy at intermediate and long-term follow-up.
      Therefore, the modified maze procedure should be offered to all mitral valve
      surgery patients and potentially to all cardiac surgery patients with a history
      of paroxysmal, persistent, or permanent atrial fibrillation.

PMID- 17008934
TI  - Planar cell polarity signaling: a common mechanism for cellular polarization.
AB  - Epithelial cells frequently display--in addition to the common apical-basolateral
      polarity--a polarization within the plane of the epithelium. This is commonly
      referred to as planar cell polarity (PCP) or tissue polarity. Examples of
      vertebrate PCP include epithelial patterning in the skin and inner ear, and also
      the morphogenetic movements of mesenchymal cells during convergent extension at
      gastrulation. In Drosophila, all adult epithelial structures of the cuticle are
      polarized within the plane. This review presents recent results and new insights
      into the molecular mechanisms underlying the establishment of PCP, and compares
      and contrasts the intriguing similarities between PCP signaling in Drosophila and
      vertebrates.

PMID- 17008936
TI  - Cardiovascular risk in the spectrum of type 2 diabetes mellitus.
AB  - The clinical importance of the metabolic syndrome is that this group of risk
      factors greatly increases the likelihood of cardiovascular events, the major
      source of disease morbidity and mortality in patients with obesity and type 2
      diabetes. Recent studies have helped clarify the mechanisms underlying the
      vascular dysfunction that leads to cardiovascular outcomes in diabetes. This
      vascular dysfunction is correlated with visceral adiposity, insulin resistance
      and alterations in the levels of a variety of circulating factors. The vascular
      effects of overt hyperglycemia also play an important role in diabetes mellitus.
      Appropriate management of diabetes in the context of the metabolic syndrome
      requires that we pay close attention to minimizing cardiovascular risk. In this
      brief review, we will cover several key concepts in the pathophysiology of type 2
      diabetes that confer increased cardiovascular risk and influence the choice of
      oral therapies for this widespread disorder.

PMID- 17008937
TI  - Phenotypic diversity in delayed drug hypersensitivity: an immunologic
      explanation.
AB  - Drug hypersensitivity reactions are a significant cause of iatrogenic-induced
      illness. (They were originally classified as type IV hypersensitivity, to
      describe the tuberculin skin reaction.) It now appears that the T-cell directs
      the entire inflammatory cascade induced by delayed drug allergy. Delayed drug
      hypersensitivity, usually manifested in the skin, is triggered when drug-specific
      CD4+ and CD8+ T cells recognize drugs through their T-cell receptors in a process
      that is dependent on a major histocompatibility complex. Drugs stimulate T-cell
      receptors by either covalently binding to peptides or using their structural
      features to interact via a more direct approach. Immunohistochemical and
      functional analysis of drug-reactive T-cell clones has shown that the phenotypic
      pattern of delayed drug hypersensitivity depends on the cytokine pattern induced.
      For example, maculo-papular exanthema may be either TH-1 or TH-2 in nature,
      depending on whether they are interferon- g /tumor necrosis factor- a or
      interleukin-4, 5 and 13 driven. Bullous reactions to drugs (i.e., Stevens-Johnson
      syndrome or toxic epidermal necrolysis) are characterized by widespread
      keratinocyte apoptosis, a consequence of high CD8+ T-cell involvement and the
      molecular cytotoxicity of Fas, perforin and granzyme B. Pustular exanthema
      reactions to medications are stimulated via the T-cell release of IL-8 and
      granulocyte-monocyte colony-stimulating factor (GM-CSF). With better
      understanding of these unique inflammatory cascades, delayed type IV
      hypersensitivity reactions have been re-classified into four main subtypes: IVa
      (TH-1/monocyte directed), IVb (TH-2/eosinophil directed), IVc (CD8+/
      Fas/perforin/Granzyme B directed) and IVd (IL-8/GM-CSF/neutrophil directed).
      Clinically, delayed hypersensitivity eruptions are often an overlap of cytokine
      pathways, with one preferential reaction dominating the final picture.

PMID- 17008938
TI  - Decrease of total antioxidant capacity during coronary artery bypass surgery.
AB  - OBJECTIVE: Cardiac surgery induces an oxidative stress, which may lead to
      impairment of cardiac function. In this study, we aimed to measure the changes of
      oxidative and antioxidative status of patients undergoing coronary artery bypass
      surgery (CABG). MATERIALS AND METHODS: We studied 79 patients who underwent CABG
      with and without cardiopulmonary bypass (CPB). Of the 79 patients, 39 had CPB and
      40 did not. Blood samples were drawn before, during, and after the surgery.
      Antioxidant status was evaluated by measuring total antioxidant capacity (TAC),
      and oxidative status was evaluated by measuring total peroxide (TP) levels and
      oxidative stress index (OSI). RESULTS: TP and OSI levels increased, while TAC
      decreased progressively after the beginning of surgery, for all patients. There
      were negative correlations between TAC levels and aortic cross-clamping period
      and anastomosis time ( r = -0.553, p < 0.001 and r = -0.500, p < 0.001,
      respectively). In addition, there was a positive correlation between TAC and
      ejection fraction (r = 0.647, p < 0.001). CONCLUSIONS: During CABG, oxidant and
      OSI levels significantly increase and TAC significantly decreases. This situation
      is influenced by long CPB and anastomosis time, and also by low ventricular
      ejection fraction. We concluded that the patients who undergo CABG are exposed to
      potent oxidative stress that impairs their TAC. We speculate that supplementation
      with antioxidant vitamins such as vitamins C and E may be beneficial for patients
      undergoing CABG.

PMID- 17008939
TI  - Surgery for hyperthyroidism in Down syndrome: case report.
AB  - Thyroid disorders are common in patients with Down syndrome (DS). In these
      patients, hyperthyroidism occurs much less frequently than hypothyroidism, but it
      is likely to be underestimated. We report a case of an adult man with DS and
      hyperthyroidism. After 2 years of antithyroid therapy in a special facility, he
      was referred to our center with recurrence of hyperthyroidism with leukopenia and
      elevations of liver enzymes 14 months after remission. The patient underwent
      subtotal thyroidectomy, with rapid preparation with inorganic iodine and
      prednisone. After thyroidectomy the patient was found to have hypothyroidism and
      was given thyroid replacement therapy. We also review the literature on the
      treatment options for hyperthyroidism with DS. We conclude that the role of
      surgery in the treatment of hyperthyroid patients with DS has yet to be defined.

PMID- 17008940
TI  - A cost-effective method for reducing the volume of laboratory tests in a
      university-associated teaching hospital.
AB  - BACKGROUND: Laboratory tests comprise a significant portion of hospital
      expenditure. Attempts to reduce their use have had mixed results. OBJECTIVE: To
      investigate the effect of an intervention based on a simple form-based system for
      ordering laboratory tests by physicians, on both use of laboratory resources and
      diagnostic accuracy. DESIGN: At Kaplan Medical Center in Rehovot , Israel , there
      are 4 similar Internal Medicine departments. In one department (C), the new
      system was initiated, whereas in the other 3 departments (A, B and D), the
      traditional method of ordering blood tests was continued. The intervention used
      was a requirement for tests to be specifically requested by residents following
      unbundling of test panels, with hands-on supervision by a senior physician. In
      addition, the residents attended a series of lectures on the economic
      implications of laboratory testing. The intervention study lasted for 3 years.
      MEASUREMENTS: Total number of tests performed in each department, number of tests
      per admission and total cost of each test at Medicare reimbursement prices.
      RESULTS: The number of tests per admission prior to the intervention was 1.91 +/-
      0.89; it decreased for each of the next 3 years: 0.76 +/- 0.61, 0.80 +/- 0.62 and
      0.78 +/- 0.63 respectively. There was a total decrease of 97,365 tests during the
      3-year period, saving 1,914,149 dollars. There was no difference in the
      readmission rate or in the number of diagnoses of conditions based primarily on
      blood tests such as hypokalemia or hyponatremia, between department C and the
      other departments. CONCLUSIONS: The intervention developed here produced
      significant and sustained reduction of financial savings in the number of
      laboratory tests ordered, without negatively impacting diagnostic capability or
      patient care.

PMID- 17008941
TI  - Comparative radiologic evaluation of percutaneous endoscopic lumbar discectomy
      and open microdiscectomy: a matched cohort analysis.
AB  - BACKGROUND: Only a few studies comparing percutaneous endoscopic discectomy and
      open discectomy have been reported in the literature. The purpose of this study
      was to compare the radiographic changes in patients treated with percutaneous
      endoscopic lumbar discectomy (PELD) with those of patients treated with open
      lumbar microdiscectomy (OLM). METHODS: A total of 30 patients who underwent PELD
      with a minimum three years of follow-up were randomly selected. To compare with
      the PELD group, 30 patients who underwent OLM during the same period were also
      randomly selected according to sex, age, and disc level. The clinical outcomes
      were evaluated by the Macnab criteria. Statistical analysis was performed using
      independent sample t-test, paired sample t-test, chi-square test, Fisher's exact
      test, and analysis of variance (ANOVA). RESULTS: The successful clinical outcomes
      were 96.7% in the PELD group and 93.3% in the OLM group. Among the various
      radiological parameters, changes of disc height (1.41 +/- 1.19 mm in the PELD
      group and 2.29 +/- 2.12 mm in the OLM group, p=0.024) and foraminal height (1.26
      +/- 0.91 mm in the PELD group and 1.85 +/- 0.92 mm in the OLM group, p=0.017)
      were significantly different between the two groups. CONCLUSIONS: Although the
      clinical outcomes were similarly satisfactory in both groups, PELD is a less
      invasive procedure than open microdiscectomy in s elected cases.

PMID- 17008942
TI  - A comparison of cardiologist and noncardiologist use of echocardiograms:
      implications for containing health care costs.
AB  - Echocardiography enables physicians to examine the heart noninvasively and
      provides a comprehensive evaluation of the cardiovascular system. However,
      because it is a relatively expensive procedure compared to an ECG or X-ray, it is
      crucial that "echo" be utilized appropriately and judiciously. Using a
      retrospective chart review, we sought to determine whether there are differences
      in concordance between the diagnoses and echo findings of cardiologists and those
      of other physicians. Due to cardiologists' greater knowledge of cardiophysiology
      and echocardiography, cardiologists were expected to have a higher concordance
      between patient diagnosis and echocardiogram findings when compared to
      noncardiology physicians. Randomly, 500 echo reports were assessed for diagnosis,
      reason for the echo, and whether the echo findings agreed with the diagnosis.
      Other criteria that were studied included whether there were additional,
      unanticipated findings and whether these findings were of major or minor
      importance. Concordance between cardiologist pre-test diagnosis and echo findings
      was found in 95 out of 175 tests (54%). Noncardiologist pre-test diagnosis
      concordance with echo findings was found in 117 out of 325 tests (36%)
      (p<0.0001). Thus, the c ardiologists were found to have a significantly higher
      concordance between diagnosis and findings on echocardiogram when compared to
      noncardiologist physicians.

PMID- 17008943
TI  - Tuberculosis of the aryepiglottic fold and sinus pyriformis: a rare entity.
AB  - Tuberculosis of the larynx and hypopharynx is an uncommon entity and rarely
      considered in the differential diagnosis of the laryngo-pharyngeal diseases. We
      describe a case of a 40-year-old man with tuberculous involvement of the
      aryepiglottic fold and medial wall of the sinus pyriformis mimicking a
      malignancy. Current literature concerning the clinical, histopathological,
      radiological and diagnostic features of this rare entity is discussed.

PMID- 17008944
TI  - Aortic occlusion in patients treated with Cisplatin-based chemotherapy.
AB  - Cisplatin-based chemotherapy is one of the most common chemotherapy regimens that
      is complicated by thromboembolic events. A wide spectrum of vascular events
      exists, including venous and arterial thromboses of varying severity and
      location. However, total occlusion of the aorta is very unusual. We describe two
      patients with atherosclerotic vascular disease who developed occlusion of the
      abdominal aorta after cisplatin-based chemotherapy.

PMID- 17008945
TI  - The diagnostic value of QT dispersion for acute coronary syndrome in patients
      presenting with chest pain and nondiagnostic initial electrocardiograms.
AB  - BACKGROUND: Patients presenting with chest pain and nondiagnostic
      electrocardiograms (ECG) in the emergency department (ED) often pose a challenge
      to physicians. QT dispersion (QTD) is an electrocardiographic marker of
      myocardial ischemia due to nonhomogenous ventricular repolarization. We
      hypothesized that QTD could accurately identify patients with acute coronary
      syndrome (ACS) who presented with chest pain and nondiagnostic initial ECGs.
      METHODS: All patients admitted to the ED with chest pain and nondiagnostic
      initial ECGs were included in the study prospectively. QTD and QTc dispersion
      (QTcD) were measured at the initial ECGs and compared for ACS patients vs. non
      ACS patients. A receiver operating characteristic curve was drawn to evaluate the
      diagnostic value of QTD and QTcD for ACS. RESULTS: Of the 137 patients with an
      initially nondiagnostic ECG, 51 were finally diagnosed with ACS (37%). Mean QTD
      and QTcD of patients with ACS were significantly greater than those of patients
      without ACS (39.61 +/- 12.9 vs. 32.56 +/- 15.1, p=0.004; 46.12 +/- 16.3 vs. 38.10
      +/- 18.2, p=0.009, respectively). The area under the curve was 0.624, p=0.015 for
      QTD, and 0.603 and p=0.049 for QTcD. When various cut-off points were evaluated,
      potentially useful values were determined between 30 and 50 ms for QTD
      (sensitivity 86% and 10%, specificity 35% and 97%, respectively). These values
      were 40.5 and 49.5 ms for QTcD (sensitivity was 96% and 32%, specificity was 12%
      and 77%, respectively). CONCLUSION: For patients with chest pain and
      nondiagnostic initial ECG, ACS risk is high if QTD and QTcD values are greater
      than 40 ms. Therefore, QTD and QTcD can help identify patients with acute
      coronary syndrome who present with chest pain and a nondiagnostic initial ECG.
      However, poor operator characteristics of QT dispersion could limit its value as
      a diagnostic test in the clinical setting.

PMID- 17008947
TI  - Isolated metachronous contralateral adrenal metastasis from renal cell carcinoma.
AB  - Isolated contralateral adrenal metastasis from renal carcinoma is extremely rare.
      Patients who present with this entity often undergo surgery with the presumed
      diagnosis of an incidentaloma. A mass in the contralateral adrenal diagnosed
      following radical nephrectomy for renal carcinoma should be viewed with a high
      index of suspicion for the presence of metastatic disease. Surgery is the only
      effective management option and should be offered to these patients.

PMID- 17008946
TI  - Surgical treatment of skier's thumb injuries: case report and review of the
      literature.
AB  - Inappropriate treatment of skier's thumb injuries has been reported to result in
      chronic painful instability, weakness of pinch, and arthritis. Therefore,
      surgical treatment is recommended for those fractures with 2 mm or more of
      displacement, or significant articular involvement with incongruency or rotation.
      The goal of surgery is restoration of anatomy with stable fixation. In this study
      we present some cases managed with internal fixation of the injury. This
      technique has the advantage of anatomic stable fixation with good outcome.

PMID- 17008948
TI  - Intestinal perforation due to miliary tuberculosis in a patient with Behcet's
      disease.
AB  - Gastrointestinal manifestations of both Behcet's disease and intestinal
      tuberculosis include the signs and symptoms of abdominal pain, weight loss,
      fever, vomiting, diarrhea and palpable mass in the right lower quadrant. We
      report the case of a male patient with Behcet's disease who had multiple ileal
      perforations due to miliary tuberculosis. It was suspected that the perforations
      were due to intestinal manifestation of Behcet's disease, but the final pathology
      report and chest X-ray one week after surgery demonstrated the presence of
      miliary tuberculosis. To our knowledge, this is the first reported case of
      Behcet's disease with intestinal perforation due to miliary tuberculosis.

PMID- 17008949
TI  - Gefitinib concentrations in human glioblastoma tissue.

PMID- 17008950
TI  - Topographic relationship between the muscle bands of the zygomaticus major muscle
      and the facial artery.
AB  - The aim of this study was to clarify the spatial relationship between the facial
      artery and the insertion of the zygomaticus major muscle in the perioral region.
      In 30 of 70 dissections (42.9%), the facial artery passed through the separate
      muscle bands of the zygomaticus major muscle. The mean diameter of the facial
      artery passing through the zygomaticus major muscle in this region was 1.74 mm
      (range 0.82-2.86 mm). The relationship between the facial artery and the
      insertion of the zygomaticus major muscle in the perioral region described in
      this study is expected to provide critical information for surgical planning and
      procedures around the perioral region.

PMID- 17008951
TI  - Anatomical bases of prolonged ilio-inguinal-hypogastric regional anesthesia.
AB  - Although anesthesia and post-operative analgesia are associated with specific
      morbidity, regional anesthesia is not systematically given during groin hernia
      surgery. The goals of this work were to determine the anatomical bases of safe
      ilio-inguinal (II)-hypogastric anesthesia that can be prolonged into the post
      operative period and to validate this technique on anatomical preparations and in
      clinical situations. We studied the courses of the ilio-hypogastric (IH) and II
      nerves in 33 halves of 20 embalmed adult cadavers. The intermediate portion of
      the IH and II nerves, located between the transverse and the internal oblique
      muscles, were found to be suitable for a simultaneous block with a single
      injection. We assessed the feasibility of injecting a percutaneous infiltration
      into this space by injecting a dye before dissection. In 75% of cases, we
      observed percutaneous coloring of the nerves, confirming that this site was
      suitable. To guide the infiltration, the points where the nerves passed through
      the transverse and the internal oblique muscles were located from the iliac crest
      and anterior and superior iliac spine, respectively. The nerve trunks were
      grouped for over 5 cm in a cell-fat layer running between these two deep muscles.
      It was possible to position a micro-catheter in this anatomical space to allow
      repeated injections. The results of this anatomical study were used to modify the
      technique so that it could be used to provide regional anesthesia in five
      patients operated on for hernia. Post-operative pain was very effectively
      controlled in four cases with no complications.

PMID- 17008953
TI  - Telerobotic surgery for right and sigmoid colectomies: 30 consecutive cases.
AB  - BACKGROUND: This study aimed to evaluate the feasibility of using a robotic
      assistant for colon resections. This report describes the experience, advantages,
      and disadvantages of using the DaVinci system for a colectomy on the basis of 30
      consecutive cases managed by a minimally invasive surgery fellowship-trained
      surgeon. METHODS: Data were prospectively collected on 30 consecutive colectomies
      performed using the DaVinci system from September 2002 to March 2005. RESULTS: A
      total of 13 sigmoid colectomies with splenic flexure mobilization and 17 right
      colectomies were performed for 14 men and 16 women. The preoperative diagnoses
      for the procedures were cancer (n = 5), diverticulitis (n = 8), polyps (n = 16),
      and carcinoid (n = 1). The right colectomies required 29.7 +/- 6.7 min (range, 22
      44 min) for the port setup, 177.1 +/- 50.6 min (range, 103-306 min) for the
      robot, and 218.9 +/- 44.6 min (range, 167-340 min) for the total case. The length
      of stay was 5.2 +/- 5.8 days (range, 2-27 days). The robot portion was 80.9% of
      the total case time. The sigmoid colectomies required 30.1 +/- 9.6 min (range, 15
      50 min) for the port setup, 103.2 +/- 29.4 min (range, 69-165 min) for the robot,
      and 225.2 +/- 37.1 min (range, 147-283 min) for the total case. The hospital
      length of stay was 6.0 +/- 7.3 days (range, 3-30 days). The robot portion was
      45.8% of the total case time. Six complications occurred: left hip paresthesia,
      cecal injury, anastomotic leak, patient slipped from the operating table after
      the robotic portion of the case, transverse colon injury, and return of a patient
      to the office with urinary retention. Two sigmoid colectomies were converted to
      laparotomy. The specific advantages and disadvantages of using the DaVinci system
      for colectomies are discussed. CONCLUSIONS: The 30 consecutive cases demonstrated
      the technical feasibility of using the DaVinci system for a colectomy. The
      longevity of the DaVinci system's use for colectomy will be determined by
      comparison of its cost and outcomes with those for conventional laparoscopic
      colectomy.

PMID- 17008952
TI  - Laparoscopic versus open approach for solitary insulinoma.
AB  - BACKGROUND: In recent years, advances in laparoscopic techniques have allowed
      surgeons to treat pancreatic lesions laparoscopically. Insulinoma, the most
      prevalent pancreatic endocrine tumor, is mostly benign and curable with surgical
      resection. This study aimed to assess the results from laparoscopic resection
      (LG) of insulinomas and to compare them with the results from open surgery (OG).
      METHODS: From September 1999 to December 2005, 56 laparoscopic pancreatic
      resections were performed for selected patients, including 12 laparoscopic
      resections of insulinomas. The results were compared with those of patients who
      underwent open resection of insulinomas selected from the authors' pancreatic
      database. RESULTS: Three conversions to the open approach were required because
      of inability to identify the tumor. There were no deaths in either group, and the
      morbidity rates were 25% (3/12) for LG and 55% (5/9) for OG (nonsignificant
      difference). The pancreatic fistula rate after laparoscopic enucleation was
      statistically lower than after open enucleation (14% vs 100%; p = 0.015). The
      mean postoperative hospital stay was 13 +/- 5.9 days for LG and 17.6 +/- 7.5 days
      for OG (nonsignificant difference). After exclusion of the patients who underwent
      conversion to laparotomy, the mean postoperative hospital stay was 11.5 +/- 5.8
      days for LG and 17.6 +/- 7.5 days for OG (p = 0.04). CONCLUSION: This study
      demonstrates the feasibility and safety of laparoscopic resection of insulinomas.
      The laparoscopic approach was associated with a decrease in hospital stay and
      pancreatic fistula after enucleation. Preoperative localization tests and
      laparoscopic ultrasonography seem necessary to prevent conversion.

PMID- 17008954
TI  - Open anterior acromioplasty for impingement syndrome.

PMID- 17008955
TI  - [Not Available].

PMID- 17008956
TI  - [Not Available].

PMID- 17008957
TI  - Upper limb tendon surgery for tetraplagia.

PMID- 17008958
TI  - [Not Available].

PMID- 17008959
TI  - [Not Available].

PMID- 17008960
TI  - [Not Available].

PMID- 17008961
TI  - [Not Available].

PMID- 17008962
TI  - [Not Available].

PMID- 17008963
TI  - [Not Available].

PMID- 17008964
TI  - [Reconstruction of complex acetabular fractures using the extensile kocher
      langenbeck approach (modified maryland approach).].
AB  - GOAL OF SURGERY: Approach to the essential bony parts of the pelvis which can be
      adapted to the fracture pattern and which causes minimal soft tissue damage. It
      allows exposure of the posterior and anterior columns and the roof of the
      acetabulum. INDICATIONS: Complex acetabular fractures such as 2-column fractures,
      T-fractures, displaced transverse fractures with posterior rim fragment,
      fractures of 1 column. CONTRAINDICATIONS: Fractures which can be approached
      through smaller incisions, preexisting lesions of the superior gluteal artery,
      arterial occlusive diseases, particularly of the pelvis. PREOPERATIVE WORK UP:
      Radiographs of the pelvis in anterior-posterior and two oblique news. Special
      radiographs and CT. POSITIONING AND ANAESTHESIA: Lateral decubitus with free
      draping of the leg. Endotracheal anaesthesia. Cell saver optional. SURGICAL
      TECHNIQUE: T-shaped skin incision and gradual extension of the Kocher-Langenbeck
      approach depending on the fracture pattern. First extensile step: Transverse
      division of the fascia lata and osteotomy of the greater trochanter. Second
      extensile step: Osteotomy of part of the iliac crest and exposure of the outer
      and inner cortex of the iliac wing. POSTOPERATIVE MANAGEMENT: Operated leg rests
      in a foam padded splint. Careful wound drainage, routine low dose radiation or
      indomethacin to prevent heterotopic ossification. CPM starting the 2nd
      postoperative day, mobilization starting the 2nd or 3rd day with partial weight
      bearing of 15 kg. Full weight bearing depends on fracture type and consolidation.
      POSSIBLE COMPLICATIONS: Delayed wound healing with risk of infection. Injury to
      the superior gluteal artery with danger of necrosis of the abductor muscles.
      Injury through stretching of the sciatic nerve. Injury of the lateral
      femorocutaneous nerve. RESULTS: Seven patients with complex acetabular fractures
      were operated between June 1993 and January 1994. Use of the 1st extensile step
      was sufficient in 3 patients and 3 times all 4 steps were used. Postoperative
      necrosis of fatty tissue necessitated 2 revisions. All fractures consolidated.
      During the follow-up examination 1 case of heterotopic ossification was seen
      (Brooker grade II). Using the classification of Merle D'Aubigne we had 1
      excellent, very good, 2 good and 1 satisfactory result.

PMID- 17008965
TI  - Correction of a malunited vertical shear fracture : Staged sliding osteotomy of
      the pelvic ring.
AB  - The authors describe a posterior and anterior osteotomy of the pelvis for
      correction of a posttraumatic deformity in a 22-year-old female patient. As a
      shortening of the leg of 4 cm had occurred, surgery was performed in 2 stages.
      Between these 2 operations skeletal traction was employed. Main indications for
      this type of surgery included shortening of the leg, gait difficulties and poor
      posture while sitting. However, poor general health is considered to be a
      contraindication for such a risky surgery. During the surgical procedure all soft
      tissues preventing an proper correction have to be dissected or detached,
      particularly the sacrospinal and sacrotuberal ligaments. Screw fixation
      guarantees the correction. Exercises can be started as soon as the fragments
      become stable. Injuries to vessels and nerves are the most frequently encountered
      complications.The patient was symptom-free after 1 year postoperatively, mobility
      of both hips and her gait were normal. The author could observe a complete
      remodelling of the osteotomies after 1 year.

PMID- 17008966
TI  - [Realignment, fusion, and staple fixation of the chopart joint in neurogenic foot
      deformities.].
AB  - GOAL OF SURGERY: Restoration of a plantigrade foot in adolescents suffering from
      a neurogenic foot deformity with an important, irreversible malposition of the
      talocalcaneonavicular joint complex. INDICATIONS: Severe, non reducible hindfoot
      deformity which cannot be corrected through soft tissue procedures alone.
      Important tarsal instability. Progressive forefoot deformities.
      CONTRAINDICATIONS: Presence of supple club foot deformities. Severe deformities
      necessitating removal of a bone wedge. Important degenerative changes of the
      subtalar joint. Presence of skin infection or sores. POSITIONING AND ANAESTHESIA:
      Supine with buttock of operated side slightly elevated. General or regional
      anaesthesia. Tourniquet at thigh. SURGICAL TECHNIQUE: Two skin incisions, one
      overlying the talonavicular and the other the calcaneoucuboid joint.
      Subperiosteal dissection until both approaches meet. Arthrodesis of the
      calcaneoucuboid and talonavicular joints after resection of articular cartilage
      and correction of deformity. Temporary fixation with Kirschner wires, visual
      control of correction and permanent fixation with titanium staples. Long leg cast
      which is split immediately. Additional tendon surgery may be necessary
      POSTOPERATIVE MANAGEMENT: Elevation of foot. Low molecular heparin. Well molded
      fibreglass cast after 2 weeks and heel added 2 weeks later. Orthopaedic shoes 10
      to 12 weeks postoperatively. POSSIBLE COMPLICATIONS: Injury of neurovascular
      structures. Pressure sores. Thrombophlebitis. Wound dehiscence, deep infection.
      Displacement or breakage of staples. Absence of bony fusion. RESULTS: Between
      August 1990 and April 1993 the technique was performed 20 times in a total of 15
      patients. Follow-up 14 to 36 months. A bony fusion occurred in all patients at 12
      weeks. Eighteen times the functional result was good to satisfactory and these
      patients were free of pain. The following complications were observed: hindfoot
      varus (2), transient loss of sensation of foot (1), necrosis of the wound edges
      (2) and breakage of the staple (1).

PMID- 17008967
TI  - Subtalar realignment in congenital clubfoot using the Cincinnati approach.
AB  - GOAL OF SURGERY: Surgical correction of clubfoot through an extensive and
      meticulous posterior, lateral, medial, subtalar, and plantar release.
      INDICATIONS: Failed conservative treatment of clubfoot at 6 months of age.
      CONTRAINDICATIONS: Previous failed surgery with a different incision.
      PREOPERATIVE WORK UP: Radiographs of both foot and ankle in the anterior
      posterior and lateral projections. POSITIONING AND ANAESTHESIA: Supine.
      Tourniquet. General anaesthesia. Free draping above the knee. SURGICAL TECHNIQUE:
      Through a Cincinnati incision the Achilles tendon is exposed and lengthened and
      the posterior capsule excised. The talofibular and the calcaneofibular ligaments
      are incised and released. The plantar aponeurosis is divided and the small
      plantar muscles are detached. Finally a medial release is achieved having excised
      the abductor hallucis muscles. Release of the dorsal talonavicular joint capsule.
      In severe cases the calcaneoucuboid joint must also be released. The corrected
      position is maintained with Kirschner wires. POSTOPERATIVE MANAGEMENT: Long leg
      cast with the knee bent at 90 degrees . Cast changed after 10 to 14 days. Eight
      weeks postoperatively removal of cast and Kirschner wires and prescription of a
      Dennis-Brown boot to be worn for 12 to 18 months. POSSIBLE COMPLICATIONS: Injury
      to neurovascular structures. Pin tract infection. Tightness, loosening or
      slipping of cast. Inadequate correction and damage to articular surfaces.
      RESULTS: From 1985 to 1992 60 infants (70 feet) were operated. Average follow-up
      was 5 years (1 to 7). Assessment of clinical and functional results was based on
      the Magone rating system: 60% excellent, 18.6% good, 11% fair results were
      obtained; 2 infants had a minor skin breakdown, 7 were undercorrected and 2 were
      overcorrected.

PMID- 17008968
TI  - [Cleft foot with Y-shaped deformity of the third metatarsus. A case history.].
AB  - GOAL OF SURGERY: Correction of the deformity of the third metatarsus and of the
      malposition of the toes to improve form and function of the foot. INDICATIONS:
      Problems with shoe wear. Aesthetic appearance. (Limitation of function.)
      CONTRAINDICATIONS: None. PREOPERATIVE WORK UP: Drawing of surgery to be
      performed. POSITIONING AND ANAESTHESIA: Supine. General anaesthesia. SURGICAL
      TECHNIQUE: Excision of the distal half of the hypoplastic second metatarsus
      through a curvilinear dorsal incision. Osteotomy of the third metatarsus at the Y
      junction and implantation of the mediodistal part into the proximal half of the
      second metatarsus. Corrective osteotomy of the third metatarsus at the Y
      junction. Internal fixation of both metatarsi with transosseous, transarticular
      Kirschner wires. Four weeks later correction of the hallux valgus using the
      technique recommended by Kramer. POSTOPERATIVE MANAGEMENT: Below knee plaster of
      Paris. Removal of K'wires after consolidation of osteotomies. Progressive
      increase in weight bearing. Arch supports. POSSIBLE COMPLICATIONS: Injury to
      nerves, vessels or tendons. Wound infection. Delayed consolidation. Nonunion.
      Growth disturbances. RESULTS: 30 months postoperatively, when the patient was 13
      years of age, both osteotomies had healed in good position: the foot looked
      nearly normal. At 21 years of age the patient has no problems. She is involved in
      sports and is satisfied with the result.

PMID- 17008969
TI  - [The endoscopic release of the transverse carpal ligament for carpal tunnel
      syndrome.].
AB  - GOAL OF SURGERY: Complete division of the flexor retinaculum for decompression of
      the medial nerve to restore normal neurologic function. INDICATIONS: Idiopathic
      and posttraumatic carpal tunnel syndrome. CONTRAINDICATIONS: Postoperative
      recurrence, carpal tunnel syndrome in patients with rheumatoid arthritis, with
      tumors or with carpal canal compromise due to bony causes. POSITIONING AND
      ANAESTHESIA: Supine General or regional anaesthesia. SURGICAL TECHNIQUE:
      Identification of the palmaris longus tendon. 1.5 cm long incision along the
      flexor crease of the wrist. If the palmaris longus is absent the incision should
      be made 1.5 cm medial to the flexor carpi radialis tendon. Introduction of the
      scope and exploration of the ulnar border of the carpal canal with a special
      instrument until the hook of the hamate has been identified. Endoscopic
      identification of the distal end of the retinaculum and insertion of the cutter.
      Complete division of the retinaculum. POSTOPERATIVE MANAGEMENT: Posterior plaster
      splint for 7 days. Elevation of the limb. Active exercises of fingers, elbow and
      shoulder and, after cast removal, also of the wrist. Lifting and carrying of
      heavy objects should be avoided for 4 to 6 weeks. POSSIBLE COMPLICATIONS: Injury
      of the median nerve or one of its branches, of the superficial palmar arch, and
      of the flexor tendons. RESULTS: Prospective randomized study of 120 patients of
      which 101 could be followed up. Forty-five patients (group A) had an open
      decompression and 47 (group B) were decompressed endoscopically. Average follow
      up period for group A 271 days, for group B 275 days. Mean age of both groups: 53
      years. There were 13 men and 41 women in group A and 17 men and 30 women in group
      B. No complications or night pain in either group. No significant difference in
      atrophy of the thenar eminence in the strength of the hand or in the 2 point
      discrimination. Results of pre- and postoperative nerve conduction and of
      temporary disability are listed in Figures 10 and 11. At follow-up 6 to 12 weeks
      postoperatively no difference could be found between the 2 groups in respect to
      scar pain, grip power and range of motion. Main advantage of the endoscopic
      approach: reduced postoperative pain and shorter disability.

PMID- 17008970
TI  - [Not Available].

PMID- 17008971
TI  - [Not Available].

PMID- 17008972
TI  - [Reconstruction of thumb through continuous lengthening of the first
      metacarpus.].
AB  - GOAL OF SURGERY: Reconstruction of the amputated thumb through continuous
      distraction with an Ilizarov ring fixator. INDICATIONS: Traumatic loss of thumb
      at the level of the proximal half of the proximal phalanx. CONTRAINDICATIONS:
      Insufficient soft tissue coverage of stump. Stiff saddle joint. POSITIONING AND
      ANAESTHESIA: Tourniquet. Brachial plexus or general anaesthesia. SURGICAL
      TECHNIQUE: Installation of a ring fixator. Incomplete osteotomy at mid shaft of
      first metacarpus with chisel and completion through osteoclasia by twisting the
      chisel. Preserve palmar periosteum. Deepening of first web space if necessary
      after removal of external fixator. Use of Z-plasty and proximal transfer of
      adductor pollicis insertion. POSTOPERATIVE MANAGEMENT: After 1 week continuous
      lengthening 0.7 mm/day in 3 daily increments. After removal of fixator plaster
      cast for 2 weeks. POSSIBLE COMPLICATIONS: Improper installation of fixator.
      Incomplete osteotomy. Too rapid or too slow distraction. Pin tract infection.
      Deep infection. RESULTS: Over a 2 year period 10 lengthenings. Average follow-up
      23 months (10 to 36 months). Average gain in length 38.1 mm. Average length of
      treatment 163 days. Deepening of web space in 7 patients. Force of grasp 64% of
      opposite side. Pin tract infection: 4, too early removal of fixator: 1, revision
      of scar: 1 and correction of stump: 1. All patients were satisfied with the
      result but for scar at web space.

PMID- 17008973
TI  - [Not Available].
AB  - In general, the desinfection of surfaces is done through scrubbing and wiping
      using substances on the basis of aldehydes, oxidants and tensides. We propose a 4
      stage procedure (see Table 1). The concentration of the agent and the duration of
      application depend on the circumstances, whether one is dealing with a
      prophylactic measure, a nosocomial infection or an infection which has to be
      reported. The epidemiologic relevance dictates the extent of desinfection.

PMID- 17008974
TI  - Drug-induced thrombocytopenia and thrombosis: evidence from patients receiving an
      oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable
      coronary Syndromes- (OPUS-TIMI 16) trial.
AB  - OBJECTIVE: To assess etiology and impact of thrombocytopenia in a large oral
      glycoprotein (GP) IIb/IIIa inhibitor trial. BACKGROUND: Heparin is known to cause
      thrombocytopenia, and in some of these patients thrombosis. GP IIb/IIIa
      inhibitors are also associated with thrombocytopenia. METHODS: The Orbofiban in
      Patients with Unstable Coronary Syndromes (OPUS-TIMI 16) Trial randomized 10,392
      patients with ACS to the oral GP IIb/IIIa inhibitor orbofiban or placebo.
      Patients were followed for a minimum of ten months. Thrombocytopenia was defined
      prospectively as a platelet count < 80,000. RESULTS: Thrombocytopenia was rare in
      the OPUS-TIMI 16 trial (0.68% at Day 30 and 0.80% at 1 year), but more common in
      patients treated with orbofiban (0.92%) compared with those treated with placebo
      (0.2%), p < 0.001. Patients who developed thrombocytopenia had higher rates of
      death (11.6% vs. 1.7%, p < 0.001), recurrent MI (12.1% vs. 2.8%, p < 0.001),
      intracranial hemorrhage (2.9% vs. 0.0%, p < 0.001), and major or severe bleeding
      (19.0% vs. 2.0%, p < 0.001) at 30 days (with similar results at one year).
      CONCLUSION: Thrombocytopenia, though uncommon, was associated with orbofiban use
      and an increased risk of bleeding, but also death and MI. This study provides
      further evidence that drugs that lead to thrombocytopenia are, in a significant
      proportion of patients associated with thrombotic events.

PMID- 17008975
TI  - The role of aspirin resistance on outcome in patients with acute coronary
      syndrome and the effect of clopidogrel therapy in the prevention of major
      cardiovascular events.
AB  - BACKGROUND: Aspirin resistance may increase up to more then threefold the risk of
      major cardiovascular events (MACE) in patients with stable coronary artery
      disease. AIM: The aim of our study was to determine; the prevalence of aspirin
      resistance in patients with acute coronary syndromes, the role of aspirin
      resistance on outcome in the follow-up and the effect of clopidogrel therapy in
      the prevention of MACE in aspirin resistant subjects. MATERIAL AND METHODS: We
      detected the prevelance of aspirin resistance in 105 patients with acute coronary
      syndrome. Platelet functions were analyzed in Platelet Function Analyzer (PFA)
      100 (Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and
      collagen and/or ADP (Col/ADP) cartridges. Primary end points of the study were
      myocardial infarction, unstable angina, cardiac death. RESULTS: 19% (n = 20) of
      patients were aspirin resistant by PFA-100. In the follow-up, MACE occured in 9
      patients (45%) with aspirin resistance and in 10 patients (11.7%) with aspirin
      sensitive platelet aggregation (p = 0.001). Multivariate analysis showed that
      aspirin resistance was an independant predictor of MACE. The prevalence of MACE
      in patients who were on clopidogrel treatment for 12 months were lower compared
      to those who were on a clopidogrel treatment for the first six months (p =
      0.040). CONCLUSIONS: We determined that the MACE risk in patients with acute
      coronary syndromes having detected aspirin resistance, was higher at
      statistically significant levels compared to patients having aspirin sensitive
      platelet aggregation. Our results showed that aspirin resistance, was an
      independant predictor of MACE in patients with acute coronary syndrome.

PMID- 17008976
TI  - Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in cancer patients with
      and without thrombosis.

PMID- 17008977
TI  - Oral anticoagulant treatment: risk factors involved in 500 intracranial
      hemorrhages.
AB  - Intracranial bleeding is the most severe complication caused by anticoagulant or
      antiplatelet treatment. The increasing use of this therapy, especially in older
      people, makes the balance between clinical benefit and bleeding risk an important
      consideration. A retrospective study of all consecutive 500 intracranial
      hemorrhages in the West Valladolid area, approximately 220,000 people, during the
      period 1998 to 2004, was performed. In relation to mortality, predisposing
      conditions were included, such as age, antithrombotic treatment, arterial
      hypertension, cancer, blood diseases, vascular malformations, and traumatisms.
      The incidence of intracranial hemorrhage was 310 per 100,000 per year with a
      mortality of 30%. Higher mortality was found in antiplatelet-treated patients
      (44.9%) than in anticoagulated patients (31.1%). This may be related to a
      different mean age of 78 vs. 71 years. Arterial hypertension was the most
      frequent risk factor (45.1% in nontreated patients, 60% anticoagulated, and 75.5%
      antiplatelet). The relative risk of intracranial bleeding in anticoagulated
      patients was 11.2 (p < 0.001) with an incidence of 0.03% and a median of 14
      months since treatment began. The median INR was 3.3. In 40% of the patients the
      previous five controls were in range. Strict consideration of indications
      criteria joined to a better control of risk factors may avoid intracranial
      bleeding episodes.

PMID- 17008978
TI  - Screening for inherited thrombophilia might be warranted among Eastern
      Mediterranean sickle-beta-0 thalassemia patients.
AB  - BACKGROUND: The role of genetic thrombophilia in the development of both micro
      and macro vascular complications in patients with hemoglobinopathies (Sickle cell
      disease and thalassemia) have been investigated with some studies negating its
      role while others suggesting it. Lebanon is known to harbor sickle cell disease,
      thalassemia and sickle beta-thalassemia hemoglobinopathy patients along with a
      documented high prevalence of genetic thrombophilia mutations. METHODS: Twelve
      sickle beta-0-thalassemia patients with no pervious history of thrombotic events
      were selected. These patients underwent a physical examination with history, echo
      Doppler, along with blood withdrawal for complete blood count and PCR analysis of
      a sample of DNA for Factor V Leiden G1691A, Factor II G20210A, and MTHFR C677T.
      Results were compared to a historical control of 50 Lebanese controls and 50
      LebaneseThalassemia Intermedia (TI) patients. RESULTS: The results showed that
      42%, 59%, and 8% of patients carried heterozygous Factor V Leiden, abnormal
      (homozygous & heterozygous) MTHFR, and heterozygous Factor II mutations
      respectively. The sickle-thalassemia patients were 5.24 and 4.39 times more
      likely to have Factor V Leiden as compared to the normal controls and TI patients
      respectively (p < 0.05). DISCUSSION: The increased prevalence of more than one
      prothrombotic genetic mutation among the group indicates a probable clustering
      phenomenon, unknown to us to which the high consanguinity rate (77%) may have
      contributed. The role of the specific MTHFR and Factor V Leiden double
      heterozygous combination in incidence, recurrence, and guidance of duration of
      therapy in VTE is not well defined in the literature despite the recognized
      higher risk of thrombosis among this patient population. Our findings suggest
      that genetic thrombophilia workup is necessary in patients with sickle-beta zero
      thalassemia presenting with thrombotic events and studies that include a larger
      number of patients are necessary in order to define specific guidelines.

PMID- 17008979
TI  - Temporal and venepuncture-related decline in circulating endothelial cell capture
      from mixed venous blood.
AB  - BACKGROUND: The quantification of circulating endothelial cells (CECs) in whole
      blood has evolved as a novel method for the assessment of endothelial function,
      although major methodological issues remain. We hypothesized that there is a
      temporal decline in CEC counts in static venesected blood and that venepuncture
      itself may lead to increased CEC detachment. METHODS: CEC isolation was performed
      using the immunobead method. For the temporal decline experiment, we included 52
      patients presenting with acute coronary syndrome (ACS). We performed CEC counts
      immediately and at 4 and 24 h later. For the venepuncture decline experiment, we
      studied 40 patients with stable cardiovascular disease (CVD). CEC counts were
      determined from the first 4 mL of aspirated venous blood and compared with counts
      obtained from a subsequent 4 mL sample of blood after at least 7.5 mL of blood
      had been collected. RESULTS: Among the ACS patients there was a significant
      temporal decline in CEC counts in static venous blood over a 24 h period (p =
      0.013). Among the patients with stable CVD, the median CEC counts obtained from
      the initial 4 mL of aspirated venous blood were significantly higher (by 32%)
      than that obtained from the later 4 mL of aspirated venous blood (p = 0.041).
      CONCLUSIONS: We demonstrated a significant temporal fall in CEC numbers in static
      venous blood over 24 h following venesection. Furthermore, we have shown that CEC
      counts are higher in the initial aspirated blood compared with that aspirated
      from the same needle subsequently. These data would have implications for how CEC
      determination is undertaken by researchers in studies related to ACS or CVD.

PMID- 17008980
TI  - Low levels of activated factor VII in systemic sclerosis.
AB  - INTRODUCTION: Recent investigations show that activated factor VII, the primary
      enzyme in the extrinsic pathway of blood coagulation, exerts additional extra
      coagulant functions, such as apoptosis and angiogenesis. On the basis of these
      recent acquisitions, the present study was aimed to evaluate activated factor VII
      in patients with systemic sclerosis and to establish a potential association with
      pathogenesis and complications of this severe autoimmune disorder. MATERIALS AND
      METHODS: Activated factor VII level was measured in twenty-eight consecutive
      scleroderma patients (2 men and 26 women, mean age 49.7 +/- 14.8 years). The main
      clinical correlates of disease, such as disease activity, renal function, skin,
      vascular and lung involvement, were evaluated by clinical and instrumental
      investigations. Activated factor VII level was also evaluated in 28 sex and age
      matched controls. RESULTS: Systemic sclerosis patients exhibited plasma activated
      factor VII activities significantly lower than those of healthy matched controls
      (15.2 versus 37.7 U/l, respectively; p < 0.001). No correlation was observed
      between plasma activated factor VII concentration and age, disease duration,
      disease subset, disease activity, renal, lung, skin and microvascular
      involvement. CONCLUSIONS: Results of our investigation provide first evidence of
      low activated factor VII activity in patients with systemic sclerosis. Reduced
      activated factor VII activity might be involved in the pathogenesis of the
      ischemic complications, by modulating apoptotic and angiogenetic processes.

PMID- 17008981
TI  - Possible mechanisms of drug-induced aspirin and clopidogrel resistance.
AB  - Aspirin (ASA) and clopidogrel have been identified as standard of care in the
      prevention of major cardiovascular events. Aspirin irreversibly inhibits the
      cyclooxygenase-1 (COX-1) enzyme, whereas non-steroidal anti-inflammatory drugs
      (NSAIDs) reversibly inhibit the COX-1 enzyme. An analysis of the literature
      revealed a statistically significant decrease in clinical benefit of ASA with
      concomitant administration of ibuprofen. Another NSAID, diclofenac, showed
      minimal effect on the inhibition of platelet aggregation when administered with
      ASA. Furthermore, the selective COX-2 inhibitor, rofecoxib, was not shown to
      influence the effect of ASA. Clopidogrel is metabolized to an active thiol
      metabolite by the CYP 3A4 enzyme. Some HMG CoA reductase inhibitors have the
      ability to inhibit the CYP 3A4 enzyme, which can result in a possible interaction
      if administered concomitantly with clopidogrel. Studies have demonstrated
      clopidogrel's platelet inhibition being significantly attenuated by atorvastatin.
      However in a post-hoc analysis, it was demonstrated that there was no difference
      in clinical outcomes between patients taking clopidogrel and HMG-CoA reductase
      inhibitors metabolized by and not metabolized by CYP 3A4. Data suggest that the
      interaction observed involving clopidogrel and HMG-CoA reductase inhibitors
      appears to be significant in-vitro. Therefore, practitioners should advise
      patients receiving chronic aspirin therapy to limit the use of ibuprofen and may
      consider concomitant administration of clopidogrel with HMG-CoA reductase
      inhibitors without regard for the drug interaction. The intent of this paper is
      to review the literature discussing possible mechanisms of drug-induced aspirin
      and clopidogrel resistance and discuss whether the interactions translate into
      clinical effects.

PMID- 17008982
TI  - Eptifibatide-induced thrombocytopenia and thrombosis.
AB  - Glycoprotein (GP) IIb/IIIa inhibitors have been shown to reduce morbidity and
      mortality in patients with acute coronary syndromes undergoing percutaneous
      coronary interventions (PCI). With their widespread use, there is a growing body
      of literature describing adverse outcomes, including severe thrombocytopenia.
      Here we report a case of a 75-year-old man who presented with an ST-elevation
      myocardial infarction, underwent primary PCI and stenting, and subsequently
      developed profound thrombocytopenia and thrombosis after eptifibatide
      administration. This report adds to the literature regarding eptifibatide-induced
      thrombocytopenia and also raises the possibility of a new syndrome of
      eptifibatide-induced thrombosis. A case is made to examine available databases
      for thrombosis after administration of eptifibatide and other GPIIb/IIIa
      inhibitors.

PMID- 17008983
TI  - Proteomics, metabolomics and circulating endothelial progenitor cells in acute
      coronary syndromes.

PMID- 17008984
TI  - Biosignatures in thrombotic disorders.

PMID- 17008985
TI  - Assessment of regional left ventricular function with multidetector-row computed
      tomography versus magnetic resonance imaging.
AB  - This study compares quantitative and qualitative information on global and
      regional left ventricular (LV) function obtained with multidetector-row computed
      tomography (MDCT) with that obtained with magnetic resonance imaging (MRI) in
      patients with a high prevalence of LV wall motion abnormalities. Thirty patients
      (19 male, 63.7+/-15.1 years) with myocardial infarction (n=12), coronary artery
      disease (n=9), arrhythmogenic right ventricular cardiomyopathy (n=6), and
      dilation cardiomyopathy (n=3) were included. Segmental LV wall motion (LV-WM) was
      assessed using a 4-point scale. Wall thickness measurements were calculated in
      diastolic and systolic short axis images. Two hundred and fifty-two out of 266
      (94.7%) normal and 189 out of 214 (88.3%) segments with decreased wall motion
      were correctly identified by MDCT, yielding a sensitivity of 88% and specificity
      of 95% for identification of wall motion abnormalities. LV-WM scores were
      identical in 86.7% of 480 segments (kappa=0.809). MDCT had a tendency to
      underestimate the degree of wall motion impairment. Interobserver agreement was
      lower in MDCT (66.5%) than in MRI (89.1%; p<0.01). Normokinetic segments are
      reliably identified with MDCT. Sensitivity for detection and accurate
      classification of LV wall motion abnormalities need to be improved. Better
      temporal resolution of the CT system seems to be the most important factor for
      enhancing MDCT performance.

PMID- 17008986
TI  - Diagnostic value of 64-slice multi-detector row cardiac CTA in symptomatic
      patients.
AB  - Cardiac multi-detector-row computed tomography (MDCT) angiography has shown high
      levels of sensitivity and especially negative predictive value regarding the
      diagnosis of coronary artery disease (CAD). This study was designed to determine
      the value of a 64-slice-MDCT scanner in comparison to invasive coronary
      angiography for the detection of CAD in a population of symptomatic patients.
      Fifty-one patients with suspected CAD underwent conventional coronary angiography
      and ECG-gated cardiac 64-slice-MDCT angiography with a rotation time of 330 ms, a
      collimation of 64x0.6 mm and a slice thickness of 0.75 mm. Blinded patient- and
      segment-based analysis was performed for the detection of stenoses >or=70% of the
      vessel lumen. 95% of all coronary segments were assessable by MDCT angiography.
      Patient-based (segment-based) analysis revealed a sensitivity of 97.8% (86.7%),
      specificity of 50% (95.2%), positive predictive value of 93.6% (75.2%) and
      negative predictive value of 75% (97.7%). Inter-rater agreement revealed a kappa
      value of 0.558 (0.722). In this symptomatic patient group a 64-slice-MDCT scanner
      shows good agreement on a segment-based analysis but only moderate agreement on a
      patient-based analysis. The diagnostic accuracy of 64-slice-MDCT coronary
      angiography is negatively influenced by the high pre-test probability of this
      symptomatic patient collective.

PMID- 17008987
TI  - Quantitative contrast-enhanced computed tomography: is there a need for system
      calibration?
AB  - The purpose of the study was to perform phantom studies to assess the impact of
      computed tomography (CT) system variability on quantitative measurements of
      contrast enhancement. A phantom containing tubes of contrast material at
      dilutions of 120, 1:35, 1:50, 1:100 and 1:200 arranged in air or water was imaged
      using 11 CT systems at 9 institutions. All systems had undergone routine
      calibration against air and water in accordance with the manufacturers'
      recommendations. For a given tube voltage, the relationship between the iodine
      concentration and CT attenuation value on a single system varied by 17 to 24%
      over 46-48 weeks. The coefficients of variance for iodine calibration factors
      across different CT systems were 8.9% in air and 5.1% in water. Calibration of
      individual CT systems for iodine response is required to allow comparison of
      quantitative measurements of contrast enhancement across different institutions.
      Using the iodine calibration factor to express contrast enhancement as iodine
      concentration would facilitate the universal application of diagnostic
      enhancement thresholds, especially if the necessary calculations were performed
      by software installed on the CT console.

PMID- 17008988
TI  - Multidetector CT (64 Slices) of the liver: examination techniques.
AB  - Sixty-four-row MDCT, although developed primarily for cardiac imaging, has the
      potential to have a great impact on liver imaging as well. Liver-imaging
      protocols with sub-millimeter collimation improve longitudinal spatial
      resolution, making the acquired dataset a real isotropic volume perfectly
      designed for optimal three-dimensional rendering and accurate organ and lesion
      volumetry. The 64-row detector array offers a wide volumetric coverage (up to 40
      mm), suitable not only for shortening scanning time and improving spatial
      resolution, but also for including a large volume per single rotation,
      particularly useful for accurate CT perfusion studies. In order to take full
      benefit from the enormous performance offered by new 64-row MDCT scanners,
      imaging protocols need to be redesigned. Due to the extremely short scanning
      window, contrast agent injection should be performed at high flow rate and
      followed by saline bolus chaser; the use of highly concentrated contrast media
      might be useful. Timing should be accurately calculated either by a test bolus
      or, better, by using an automatic bolus-detection technique. Radiation exposure
      is kept under control, using automatic device-modulating dose delivery according
      to the patient's anatomy. Finally, the evaluation of acquired volumetric datasets
      needs the extensive use of a dedicated workstation, with software with
      sophisticated rendering capabilities.

PMID- 17008991
TI  - Molecular genetic characterization of the Lr34/Yr18 slow rusting resistance gene
      region in wheat.
AB  - Wheat expressed sequence tags (wESTs) were identified in a genomic interval
      predicted to span the Lr34/Yr18 slow rusting region on chromosome 7DS and that
      corresponded to genes located in the syntenic region of rice chromosome 6
      (between 2.02 and 2.38 Mb). A subset of the wESTs was also used to identify
      corresponding bacterial artificial chromosome (BAC) clones from the diploid D
      genome of wheat (Aegilops tauschii). Conservation and deviation of micro
      colinearity within blocks of genes were found in the D genome BACs relative to
      the orthologous sequences in rice. Extensive RFLP analysis using the wEST derived
      clones as probes on a panel of wheat genetic stocks with or without Lr34/Yr18
      revealed monomorphic patterns as the norm in this region of the wheat genome. A
      similar pattern was observed with single nucleotide polymorphism analysis on a
      subset of the wEST derived clones and subclones from corresponding D genome BACs.
      One exception was a wEST derived clone that produced a consistent RFLP pattern
      that distinguished the Lr34/Yr18 genetic stocks and well-established cultivars
      known either to possess or lack Lr34/Yr18. Conversion of the RFLP to a codominant
      sequence tagged site (csLV34) revealed a bi-allelic locus, where a variant size
      of 79 bp insertion in an intron sequence was associated with lines or cultivars
      that lacked Lr34/Yr18. This association with Lr34/Yr18 was validated in wheat
      cultivars from diverse backgrounds. Genetic linkage between csLV34 and Lr34/Yr18
      was estimated at 0.4 cM.

PMID- 17008990
TI  - Local staging of rectal cancer: the current role of MRI.
AB  - With the advent of powerful gradient coil systems and high-resolution surface
      coils, magnetic resonance imaging (MRI) has recently extended its role in the
      staging of rectal cancer. MRI is superior to endorectal ultrasound, the most
      widely used staging modality in patients with rectal tumors, in that it
      visualizes not only the intestinal wall but also the surrounding pelvic anatomy.
      The crucial advantage of MRI is not that it enables exact T-staging but precise
      evaluation of the topographic relationship of a tumor to the mesorectal fascia.
      This fascia is the most important anatomic landmark for the feasibility of total
      mesorectal excision, which has evolved into the standard operative procedure for
      the resection of cancer located in the middle or lower third of the rectum. MRI
      is currently the only imaging modality that is highly accurate in predicting
      whether or not it is likely that a tumor-free margin can be achieved and thus
      provides important information for planning of an effective therapeutic strategy,
      especially in patients with advanced rectal cancer.

PMID- 17008989
TI  - Breast MR imaging in women at high-risk of breast cancer. Is something changing
      in early breast cancer detection?
AB  - In the last few years, several papers have addressed the introduction of contrast
      enhanced MR imaging for screening women at high risk for breast cancer. Taking in
      consideration five prospective studies, on 3,571 screened women with hereditary
      predisposition to the disease and 9,652 rounds, we found that 168 patients were
      diagnosed with breast cancer (155 screen-detected, eight interval, and five
      cancers excluded from analysis) with a detection rate per year of 1.7%. These
      cancers were small (49% equal to or less than 10 mm in diameter) but aggressive,
      82% being invasive and 49% with histologic grade 3; however, only 19% of these
      invasive cancers were associated with nodal involvement. The pooled sensitivity
      was 16% for clinical breast examination, 40% for mammography, 43% for ultrasound,
      and 81% for MR. The positive predictive value (calculated on the basis of the
      number of invasive diagnostic procedures due to false positives) was 33%, 47%,
      18%, and 53%, respectively. Aim of the present article is to present the
      historical development of MR imaging of breast tumors that made this application
      theoretically and technically possible, to explain what strategic problems we
      face in the presence of a hereditary predisposition to the disease, to review the
      main results of the published studies, and to outline open problems and future
      perspectives.

PMID- 17008992
TI  - Study of the three-way interaction between Trichoderma atroviride, plant and
      fungal pathogens by using a proteomic approach.
AB  - The main molecular factors involved in the complex interactions occurring between
      plants (bean), two different fungal pathogens (Botrytis cinerea, Rhizoctonia
      solani) and an antagonistic strain of the genus Trichoderma were investigated.
      Two-dimensional (2-D) electrophoresis was used to analyze separately collected
      proteomes from each single, two- or three-partner interaction (i.e., plant,
      pathogenic and antagonistic fungus alone and in all possible combinations).
      Differential proteins were subjected to mass spectrometry and in silico analysis
      to search for homologies with known proteins. In the plant proteome, specific
      pathogenesis-related proteins and other disease-related factors (i.e., potential
      resistance genes) seem to be associated with the interaction with either one of
      the two pathogens and/or T. atroviride. This finding is in agreement with the
      demonstrated ability of Trichoderma spp. to induce systemic resistance against
      various microbial pathogens. On the other side, many differential proteins
      obtained from the T. atroviride interaction proteome showed interesting
      homologies with a fungal hydrophobin, ABC transporters, etc. Virulence factors,
      like cyclophilins, were up-regulated in the pathogen proteome during the
      interaction with the plant alone or with the antagonist too. We isolated and
      confidently identified a large number of protein factors associated to the multi
      player interactions examined.

PMID- 17008993
TI  - PpRT1: the first complete gypsy-like retrotransposon isolated in Pinus pinaster.
AB  - We have isolated and characterized a complete retrotransposon sequence, named
      PpRT1, from the genome of Pinus pinaster. PpRT1 is 5,966 bp long and is closely
      related to IFG7 gypsy retrotransposon from Pinus radiata. The long terminal
      repeats (LTRs) have 333 bp each and show a 5.4% sequence divergence between them.
      In addition to the characteristic polypurine tract (PPT) and the primer binding
      site (PBS), PpRT1 carries internal regions with homology to retroviral genes gag
      and pol. The pol region contains sequence motifs related to the enzymes protease,
      reverse transcriptase, RNAseH and integrase in the same typical order known for
      Ty3/gypsy-like retrotransposons. PpRT1 was extended from an EST database sequence
      indicating that its transcription is occurring in pine tissues. Southern blot
      analyses indicate however, that PpRT1 is present in a unique or a low number of
      copies in the P. pinaster genome. The differences in nucleotide sequence found
      between PpRT1 and IFG7 may explain the strikingly different copy number in the
      two pine species genome. Based on the homologies observed when comparing LTR
      region among different gypsy elements we propose that the highly conserved LTR
      regions may be useful to amplify other retrotransposon sequences of the same or
      close retrotransposon family.

PMID- 17008994
TI  - Patagonian wines: implantation of an indigenous strain of Saccharomyces
      cerevisiae in fermentations conducted in traditional and modern cellars.
AB  - In this work we evaluate the implantation capacity of the selected S. cerevisiae
      indigenous strain MMf9 and the quality of the produced wines in a traditional (T)
      and a modern (M) cellar with different ecological and technological
      characteristics in North Patagonia (Argentina). Red musts were fermented in
      10,000 l vats using the indigenous strain MMf9 as well as the respective
      controls: a fermentation conducted with a foreign starter culture (BC strain) in
      M cellar and a natural fermentation in T cellar. Since commercial S. cerevisiae
      starters are always used for winemaking in M cellar and in order to compare the
      results, natural fermentations and fermentations conducted by the indigenous
      strain MMf9 were performed at pilot (200 l) scale in this cellar, concomitantly.
      Thirty indigenous yeasts were isolated at three stages of fermentation: initial,
      middle and end. The identification of the yeast biota associated to vinifications
      was carried out using ITS1-5.8S-ITS2 PCR-RFLP. The intra-specific variability of
      the S. cerevisiae populations was evaluated using mtDNA-RFLP analysis. Wines
      obtained from all fermentations were evaluated for their chemical and volatile
      composition and for their sensory characteristics. A higher capacity of
      implantation of the indigenous MMf9 strain was evidenced in the fermentation
      carried out in M cellar (80% at end stage) than the one carried out in T cellar
      (40%). This behaviour could indicate that each cellar differs in the diversity of
      S. cerevisiae strains associated to wine fermentations. Moreover a higher
      capacity of implantation of the native starter MMf9 with regard to the foreign
      (BC) one was also found in M cellar. The selected indigenous strain MMf9 was able
      to compete with the yeast biota naturally present in the must. Additionally, a
      higher rate of sugar consumption and a lower fermentation temperature were
      observed in vinifications conducted by MMf9 strain with regard to control
      fermentations, producing wines with favourable characteristics. Even when its
      implantation in T fermentation was lower than that observed in M one, we can
      conclude that the wine features from MMf9 fermentations were better than those
      from their respective controls. Therefore, MMf9 selected indigenous strain could
      be an interesting yeast starter culture in North Patagonian wines.

PMID- 17008995
TI  - Intravenous immunoglobulins for the management of Stevens-Johnson syndrome with
      minimal skin manifestations.
AB  - Here we describe the successful use of intravenous immunoglobulin (IVIG) in the
      management of mycoplasma-induced, atypical Stevens-Johnson syndrome (SJS) with
      minimal skin manifestations. The patient was successfully managed with high-dose
      IVIG 0.5 g/kg for 4 consecutive days. No complications were noted. IVIG may be
      useful in the management of mycoplasma-induced SJS.

PMID- 17008996
TI  - Should healthy children be vaccinated against influenza? Comments about this
      query.

PMID- 17008997
TI  - Pitfalls in the approach to pica.

PMID- 17008998
TI  - Conservative management of pneumatosis intestinalis following haematopietic stem
      cell transplantation for major beta thalassemia.

PMID- 17008999
TI  - Alveolar rhabdomyosarcoma mimicking lymphoma with bone marrow involvement.

PMID- 17009000
TI  - Henoch-Schonlein purpura presenting duodenal involvement similar to superior
      mesenteric artery syndrome in a girl.
AB  - Henoch-Schonlein purpura (HSP) is an inflammatory vasculitis involving the skin,
      joints, gastrointestinal (GI) tract, and kidneys. This is the first case report
      describing a 5-year-old girl with HSP presenting duodenal involvement which might
      be associated with superior mesenteric artery syndrome (SMAS).

PMID- 17009001
TI  - Characterization of volatile organic compounds and odors by in-vivo sampling of
      beef cattle rumen gas, by solid-phase microextraction, and gas chromatography
      mass spectrometry-olfactometry.
AB  - Volatile organic compounds (VOCs) and odors in cattle rumen gas have been
      characterized by in-vivo headspace sampling by solid-phase microextraction (SPME)
      and analysis by gas chromatography-mass spectrometry-olfactometry (GC-MS-O). A
      novel device enabling headspace SPME (HS-SPME) sampling through a cannula was
      designed, refined, and used to collect rumen gas samples from steers. A Carboxen
      polydimethylsiloxane (PDMS) fiber (85 microm) was used for SPME sampling. Fifty
      VOCs from ten chemical groups were identified in the rumen headspace. The VOCs
      identified had a wide range of molecular weight (MW) (34 to 184), boiling point (
      63.3 to 292 degrees C), vapor pressure (1.05x10(-5) to 1.17x10(2) Pa), and water
      solubility (0.66 to 1x10(6) mg L-1). Twenty-two of the compounds have a published
      odor detection thresholds (ODT) of less than 1 ppm. More than half of the
      compounds identified are reactive and have an estimated atmospheric lifetime of
      <24 h. The amounts of VFAs, sulfide compounds, phenolic compounds, and skatole,
      and the odor intensity of VFAs and sulfide compounds in the rumen gas were all
      higher after feeding than before feeding. These results indicate that rumen gases
      can be an important potential source of aerial emissions of reactive VOCs and
      odor. In-vivo sampling by SPME then GC-MS-O analysis can be a useful tool for
      qualitative characterization of rumen gases, digestion, and its relationship to
      odor and VOC formation.

PMID- 17009002
TI  - Trends in the analytical applications of chemiluminescence in the liquid phase.

PMID- 17009003
TI  - How can immunochemical methods contribute to the implementation of the Water
      Framework Directive?
AB  - Immunochemical methods (in particular immunoassays) have been applied to spring
      and surface water samples, respectively, which were set-up as reference materials
      (RM) within two proficiency testing campaigns. For the first set of proficiency
      tests (PTs) described here (which were actually the second round of PTs
      organized, spring 2005), three ELISAs (enzyme-linked immunosorbent assays) were
      employed in the enzyme tracer format for isoproturon, diuron, and atrazine,
      respectively. Results were evaluated in comparison with conventional reference
      methods (LC, GC). Based on their Z-score laboratory performances, the results for
      isoproturon and diuron were satisfactory, both for fortified spring water and for
      the blind solution. The results for atrazine were strongly influenced by other
      triazines present and needed detailed interpretation. For the second set of PTs
      described here (which were actually the third round of PTs organized, spring
      2006), two ELISAs in the coating antigen format were used for isoproturon and
      diuron, and the result was included with the results obtained by conventional
      methods during the PTs. The results (the Z-scores) for isoproturon were again
      classified as satisfactory, in both fortified surface water and blind solution.
      The results for diuron in ELISA showed an influence of the water matrix, while
      the analysis of the blind solution was satisfactory. In addition, an ELISA in the
      enzyme tracer format was applied to analyze isoproturon, diuron, and atrazine in
      surface water samples, which had been set-up and spiked during a field trial
      (tank experiment) at the Maas River at Eijsden, The Netherlands. The immunoassay
      results were compared with those from an in-house on-line SPE LC/MS-MS used as
      reference. Although the immunochemical results were sometimes higher than those
      determined in the reference analysis, the general concentration trends in the
      samples were similar. The contribution of immunochemical methods to the
      implementation of the European Water Framework Directive is also discussed.

PMID- 17009004
TI  - Optical biochemical and chemical sensors--Europt(r)ode VIII.

PMID- 17009005
TI  - ["In the beginning was the word...": language and medicine].
AB  - The attempt to thoroughly comprehend words used in medicine inevitably leads into
      the prophetic maelstrom of the poet. In psychotherapy and medicine attempts are
      made to heal or alleviate suffering through the concrete relationship between two
      people. Substantial support is achieved by the occupation with questions of
      religion, art and literature and to attain the necessary caution with the
      knowledge of how difficult it is to put feelings into words, especially at the
      sickbed.

PMID- 17009006
TI  - Transient ventriculoperitoneal shunt malfunction after chronic constipation: case
      report and review of literature.
AB  - BACKGROUND: Significant constipation in patients with shunt-dependent
      hydrocephalus may often be enough to bring a subclinical shunt malfunction to
      clinical attention or even to be the cause of temporary distal peritoneal shunt
      malfunction. The treatment of the constipation may address the symptomatic shunt
      dysfunction so as to avoid operative intervention. The pathogenesis of distal
      shunt malfunction and its management in such a situation are discussed, and the
      relevant literature is briefly reviewed. CASE REPORT: A 16-year-old young boy had
      shunt-dependent hydrocephalus secondary to prematurity and intraventricular
      hemorrhage at birth. He was chronic flaccid paraplegic and had a neurogenic
      bladder and bowel involvement. He presented with acute dull aching intermittent
      headaches, nausea, and constipation of short duration. There was no underlying
      shunt infection. CT brain showed dilated lateral ventricles. Shunt survey
      revealed a convoluted course and kink in the distal peritoneal catheter. After
      administration of a bowel enema, the headaches and nausea resolved over the next
      few hours, and the posttreatment CT showed significant decrease in ventricular
      size. CONCLUSION: Chronic constipation is an important predisposing factor for
      distal malfunction in shunt-dependent hydrocephalus and should be ascertained in
      evaluation of a ventriculoperitoneal shunt malfunction. Appropriate treatment of
      significant constipation can relieve shunt malfunction and reestablish
      cerebrospinal fluid circulation. A shunt exploration can be avoided in such a
      situation. A close neurological monitoring of the patient is essential during the
      course of treatment. An interdisciplinary approach between concerned medical
      specialties and enhanced awareness is mandatory to ensure appropriate bowel
      management.

PMID- 17009007
TI  - Fatal glioblastoma multiforme in a patient with neurofibromatosis type I: the
      dilemma of systematic medical follow-up.
AB  - INTRODUCTION: Neurofibromatosis type I (NF1) is one of the most prevalent genetic
      diseases of the nervous system. Although the majority of NF1 patients are only
      mildly affected, the risk of developing malignancies is significantly increased
      in this population. CASE REPORT: Here, we present a 9-year-old girl with clinical
      stigmata of NF1 and a rapidly evolving glioblastoma multiforme. Molecular genetic
      analysis uncovered a novel missense mutation in Exon 32 of the NF1 gene
      [c.6032C>A(p.Ala2011Glu)]. DISCUSSION: The girl's death 3 days after diagnosis of
      the brain tumor exemplifies that NF1 still is a life-threatening disease despite
      its generally benign course in most patients. However, it remains questionable if
      a fatal course as reported here can be prevented by routine MRI screening.

PMID- 17009008
TI  - Trimyelia with divergent cord pathways and three foramina magni.
AB  - OBJECT: We report the rare finding of trimyelia with divergent cord pathways in a
      33 5/7-week-old fetus who died shortly after spontaneous vaginal delivery.
      METHODS: The main autopsy findings were three separate and distinct spinal cords,
      arising from the medulla and exiting through three separate foramina magni. The
      two lateral cords coursed toward each upper extremity and the medulla split into
      two halves that rejoined to form a central cervical cord. Further evaluation of
      this anomaly revealed agenesis of the cerebellar vermis and cystic dilation of
      the fourth ventricle. Microscopic cross-sections of the two lateral cords
      demonstrated well-formed central canals, white matter, and central gray with
      motor neurons. Sections of the abnormal mid-cervical cord demonstrated abnormally
      structured cord parenchyma without central canals. CONCLUSIONS: Some features
      were consistent with iniencephaly; however, defects of the occipital bone,
      anterior spina bifida, and shortening of the spinal cord were absent. Although
      agenesis of the cerebellar vermis and cystic dilation of the fourth ventricle
      indicate Dandy-Walker syndrome, other features such as hydrocephalus, agenesis of
      the corpus callosum, infundibular hamartomas, and malformations of the inferior
      olives or an occipital encephalocele were absent. The possible pathogenesis of
      this intriguing pathological entity is briefly discussed.

PMID- 17009009
TI  - Preoperative radiation therapy for locally advanced rectal cancer: a comparison
      between two different time intervals to surgery.
AB  - BACKGROUND: Although it is now considered a standard treatment to irradiate an
      advanced mid or low rectal tumor before surgical total mesorectal excision (TME),
      the optimal time interval between radiation therapy and surgery remains
      controversial. MATERIALS AND METHODS: Between 1995 and 2005, patients undergoing
      preoperative radiation therapy and TME for locally advanced mid and low rectal
      tumors treated in the VU Medical Center or the Zaans Medical Center were entered
      into this study. All patients received identical radiation treatment in the VU
      Medical Center and were subsequently operated on within 2 weeks in the Zaans
      Medical Center (SI group) and after 6-8 weeks in the VU Medical Center (LI
      group). Preoperative tumor staging, operative data, postoperative complications,
      pathology results, and follow-up were compared. RESULTS: The SI group (N=57)
      underwent surgery after a median delay of 4 days and the LI group (N=51) after 45
      days. Operative data and short-term morbidity were comparable for both groups.
      However, significantly higher numbers of complete remissions (12 vs 0%), tumor
      downstaging (55 vs 26%), and less lymph-node metastases (22 vs 44%) were found in
      the LI group. No significant differences were found regarding local control or
      long-term survival after a median follow-up of 34 months. CONCLUSION: Several
      advantages, such as complete remissions and downstaging in the LI group, do not
      appear to have expression in a better survival or less local recurrences after a
      median follow-up of 34 months. Although larger (randomized) studies will be
      needed for definite conclusions, this may indicate that patients can be operated
      on within 2 weeks after radiation therapy.

PMID- 17009010
TI  - The role of protein kinase CK2 in intestinal epithelial cell inflammatory
      signaling.
AB  - BACKGROUND: The transcription factor NF-kappaB is believed to play a key
      pathophysiological role in chronic intestinal inflammation. Further
      characterization of its mechanism of regulation, predominantly through cell
      signaling pathways, may provide clues as to the means of its intervention. One
      such potential signaling candidate is the protein kinase CK2. Despite its known
      ability to influence NF-kappaB activation, it has received no attention in this
      particular setting. AIM: To characterize the aspects of its activation in
      response to IL-1beta in the colonic cell lines Caco2 and HCT116. MATERIALS AND
      METHODS: A biochemical analysis of kinase activation was performed using phospho
      specific antibodies as well as immune complex kinase assays; transcription factor
      activity was measured by transient transfection and luciferase-based NF-kappaB
      reporter assays; pro-inflammatory molecule expression was determined using RT
      PCR. RESULTS: In this report, we show an enhanced activation of CK2 bound to
      IKKgamma or the p65 subunit of the NF-kappaB in response to IL-1beta stimulation
      of intestinal epithelial cells. Using two established NF-kappaB reporters, we
      demonstrate that CK2 is involved in NF-kappaB regulation through the p65 serine
      529 site. Using co-immunoprecipitation studies, we also show that p65 is bound to
      CK2 predominantly in the nucleus. From a functional perspective, two CK2 specific
      inhibitors were then shown to attenuate IL-8 reporter activation. Finally, the
      expression of a series of pro-inflammatory molecules including IL-8, GRO-alpha,
      MCP-1, TNFalpha and iNOS were variably affected in response to CK2 inhibition.
      CONCLUSION: CK2 plays an active role in NF-kappaB signaling in intestinal
      epithelial cell lines and may represent a possible target for intervention.

PMID- 17009011
TI  - High efficiency and throughput system in directed evolution in vitro of reporter
      gene.
AB  - In vitro directed evolution, especially with DNA shuffling, is a powerful means
      in biological studies of protein structure and function, and consequently for
      industrial applications. Escherichia coli beta-glucuronidase (gusA) gene, a
      versatile and efficient reporter gene, was the model for studying in vitro
      directed evolution because of its stability, easy analysis of the enzyme
      properties and conveniently visible phenotype. We developed a high efficiency,
      throughput system for in vitro directed evolution using gusA reporter gene as the
      model. The system consisted mainly of three aspects: a prokaryotic expression
      vector pYPX251, an easy method for obtaining the mutated gene from DNA shuffling
      and a suitable selected strategy. The vector pYPX251 carried the moderately
      strong aacC1 gene promoter and T1T2 transcription terminator that allowed
      expression in E. coli. Over 10,000 individuals could be selected individually in
      a 9 cm Petri dish after colonies were absorbed on a nitrocellulose filter. A
      library, which contained 100,000 individuals was screened by incubating ten
      filter papers with X-Glu. The polymerase chain reaction products of the gusA
      gene, the fragments of 50-100 bp, with high mutation rates were purified using a
      dialysis bag from 10% PAGE after electrophoresis. The possibility of obtaining
      desirable mutations was increased dramatically as the size of the library
      expanded. A GUS variant, named GUS-TR, was obtained through this system, which is
      significantly more resistant to high temperature than the wild type enzyme. GUS
      TR maintained its high activity even when the nitrocellulose filter containing
      the variant colony was heated at 100 degrees C for 30 min.

PMID- 17009012
TI  - The effects of solar radiation on thermal comfort.
AB  - The aim of this study was to investigate the relationship between simulated solar
      radiation and thermal comfort. Three studies investigated the effects of (1) the
      intensity of direct simulated solar radiation, (2) spectral content of simulated
      solar radiation and (3) glazing type on human thermal sensation responses. Eight
      male subjects were exposed in each of the three studies. In Study 1, subjects
      were exposed to four levels of simulated solar radiation: 0, 200, 400 and 600 Wm(
      2). In Study 2, subjects were exposed to simulated solar radiation with four
      different spectral contents, each with a total intensity of 400 Wm(-2) on the
      subject. In Study 3, subjects were exposed through glass to radiation caused by
      1,000 Wm(-2) of simulated solar radiation on the exterior surface of four
      different glazing types. The environment was otherwise thermally neutral where
      there was no direct radiation, predicted mean vote (PMV)=0+/-0.5, [International
      Standards Organisation (ISO) standard 7730]. Ratings of thermal sensation,
      comfort, stickiness and preference and measures of mean skin temperature (t(sk))
      were taken. Increase in the total intensity of simulated solar radiation rather
      than the specific wavelength of the radiation is the critical factor affecting
      thermal comfort. Thermal sensation votes showed that there was a sensation scale
      increase of 1 scale unit for each increase of direct radiation of around 200 Wm(
      2). The specific spectral content of the radiation has no direct effect on
      thermal sensation. The results contribute to models for determining the effects
      of solar radiation on thermal comfort in vehicles, buildings and outdoors.

PMID- 17009013
TI  - Periventricular echodensities in preterm infants.

PMID- 17009015
TI  - Reactive Legionella pneumophila arthritis diagnosed by polymerase chain reaction.

PMID- 17009014
TI  - Activation of MKK4 (SEK1), JNK, and c-Jun in labial salivary infiltrating T cells
      in patients with Sjogren's syndrome.
AB  - We wanted to determine via immunohistochemistry, whether or not c-Jun NH2
      terminal kinase (JNK) cascade is activated in labial salivary infiltrating T
      cells in patients with Sjogren's syndrome (SS). Six patients with primary SS were
      selected for this study. Phosphorylation of mitogen-activated protein kinase
      (MAPK) kinase 4 (MKK4) (SEK1), JNK, and c-Jun in salivary infiltrating T cells
      was studied using immunohistochemistry assay, including mirror section technique.
      Phosphorylated forms of MKK4, JNK, and c-Jun were detected in salivary
      infiltrating mononuclear cells. Expression of phosphorylated JNK was found in
      both CD4+ T cells and CD8+ T cells. Moreover, co-expression of phosphorylated JNK
      and c-Jun was demonstrated in the mirror sections. The results of this study
      suggest that the JNK cascade is activated in salivary infiltrating CD4+ T cells
      and CD8+ T cells in SS patients, which appears to contribute to the inflammatory
      salivary microenvironment of SS.

PMID- 17009016
TI  - Is measurement of IgM and IgA rheumatoid factors (RF) in juvenile rheumatoid
      arthritis clinically useful?
AB  - The prevalence and clinical relevance of IgM and IgA RF detected by ELISA were
      studied in 91 patients with juvenile rheumatoid arthritis (JRA) and 45 healthy
      children. IgM and IgA RF were detected, respectively, in 33 and 44% of the
      patients, compared to 6.7 and 15.6% of the healthy children (p = 0.001 and
      0.0006, respectively). The frequency of IgM RF was significantly higher in
      patients with polyarticular (52%) as compared to systemic onset JRA (21%; p =
      0.04). Five out of ninety-one patients and none of the control group were IgM RF
      positive by the latex test. High levels of IgM RF were detected more frequently
      in patients with active disease (p = 0.01) and positive latex agglutination test
      (p < 0.001) and had a marginally significant association with severe radiological
      deformities (p = 0.05). The presence of IgA RF was associated with active disease
      in polyarticular onset JRA children (p = 0.04). In conclusion, high levels of IgM
      RF and the detection of IgA RF can be useful in assessing clinical activity in a
      subset of patients with JRA.

PMID- 17009017
TI  - Accelerated apoptosis in SLE neutrophils cultured with anti-dsDNA antibody
      isolated from SLE patient serum: a pilot study.
AB  - Increased numbers of apoptotic neutrophils are found in SLE, related to disease
      activity and levels of anti-dsDNA antibody. The mechanism of increased apoptosis
      is not clear, but anti-dsDNA antibody has been shown to induce apoptosis in
      neutrophils from normal subjects and in certain cell lines. In this study,
      polyclonal anti-dsDNA antibody was isolated from the serum of a patient with
      active SLE, and was shown to substantially accelerate apoptosis in neutrophils
      from SLE patients as compared with neutrophils from healthy control or rheumatoid
      arthritis subjects.

PMID- 17009018
TI  - Descending necrotising mediastinitis: a safe treatment algorithm.
AB  - Descending necrotising mediastinitis can complicate oropharyngeal infection and
      has a high associated mortality. We present three cases treated in our department
      and propose a treatment algorithm based on our experience and literature review.
      The primary oropharyngeal infection was peritonsillar abscess in two cases and
      odontogenic abscess in one. Two patients underwent cervicotomy and later
      thoracotomy. The third underwent cervicotomy with transcervical mediastinal
      drainage and later required pericardial drainage via a subxiphoid incision. All
      recovered fully and were discharged within 6 weeks. To enable successful
      treatment, diagnosis needs to be prompt and surgical drainage adequate. Thoracic
      management of the chest is essential.

PMID- 17009019
TI  - Atypical lipomatous tumors of the face: a controversial issue.
AB  - We reviewed the topic of atypical lipomatous tumors including definition,
      diagnosis and management, with special emphasis on head and neck location and to
      report on the management of a rare case located in the temporalis muscle.
      Atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLS) are rarely
      reported in the head and neck. Their behavior dictates a complete resection.
      Resection with a safety margin is sometimes needed according to the histological
      characteristics. Tumors located to the masticator space can be accessed through a
      mucosal approach achieving relative safety to the facial nerve. ALT constitute a
      group of tumors of a borderline behavior. Their management can be affected by
      some histological criteria and by their location in the head and neck region
      where vital structures can be affected.

PMID- 17009020
TI  - Revision surgeries in cochlear implant patients: a review of 45 cases.
AB  - The aim of this study was to analyze the causes for revision procedures, surgical
      findings and audiological outcome in reoperated cochlear implant patients. The
      medical records of 45 patients were reviewed retrospectively for age at the time
      of implantation, the implant was used for initial and revision surgeries, the
      duration of implant use before revision, surgical findings, and postoperative
      audiological results. Generally, children were reoperated more often than adults
      (12.5 vs. 6.9%) and, with one exception of improper electrode insertion, there
      were no major post-revision complications. Device failure (DF) was the main cause
      for revision surgery (23/45) followed by wound/flap problems, magnet/receiver
      stimulator displacement, foreign body/allergic reaction, subperiosteal abscess,
      misplaced electrode, intractable vertigo, cholesteatoma and extrusion of the
      positioner. No significant difference was found in the rate of DF between
      children and adults for each implant separately (P = 0.289 for Nucleus 22, P =
      0.355 for Nucleus 24, P = 0.683 for Clarion and P = 1.0 for Med-El). The failure
      rates of different implants did not differed significantly among adults. DF in
      the Clarion group was significantly higher compared to the Nucleus and Med-El
      combined for pediatric patients (P = 0.0218) and all CI recipients (adults +
      children; P = 0.0055). The post-revision audiological benefit was unchanged or
      improved compared to the initial implantation values in all reimplanted patients
      and was not influenced by minor surgical procedures (wound revision, drainage of
      any collection, magnet replacement, or relocation of receiver-stimulator). Since
      DF was found to be the most common cause for reoperation, improving device
      technology could prevent the vast majority of revision procedures.

PMID- 17009021
TI  - A cryptic type I polyketide synthase (cpk) gene cluster in Streptomyces
      coelicolor A3(2).
AB  - The chromosome of Streptomyces coelicolor A3(2), a model organism for the genus
      Streptomyces, contains a cryptic type I polyketide synthase (PKS) gene cluster
      which was revealed when the genome was sequenced. The ca. 54-kb cluster contains
      three large genes, cpkA, cpkB and cpkC, encoding the PKS subunits. In silico
      analysis showed that the synthase consists of a loading module, five extension
      modules and a unique reductase as a terminal domain instead of a typical
      thioesterase. All acyltransferase domains are specific for a malonyl extender,
      and have a B-type ketoreductase. Tailoring and regulatory genes were also
      identified within the gene cluster. Surprisingly, some genes show high similarity
      to primary metabolite genes not commonly identified in any antibiotic
      biosynthesis cluster. Using western blot analysis with a PKS subunit (CpkC)
      antibody, CpkC was shown to be expressed in S. coelicolor at transition phase.
      Disruption of cpkC gave no obvious phenotype.

PMID- 17009022
TI  - Peroxidase activity of selenoprotein GrdB of glycine reductase and stabilisation
      of its integrity by components of proprotein GrdE from Eubacterium
      acidaminophilum.
AB  - The anaerobe Eubacterium acidaminophilum has been shown to contain an
      uncharacterized peroxidase, which may serve to protect the sensitive
      selenoproteins in that organism. We purified this peroxidase and found that it
      was identical with the substrate-specific "protein B"-complex of glycine
      reductase. The "protein B"-complex consists of the selenocysteine-containing GrdB
      subunit and two subunits, which derive from the GrdE proprotein. The specific
      peroxidase activity was 1.7 U (mg protein)(-1) with DTT and cumene hydroperoxide
      as substrates. Immunoprecipitation experiments revealed that GrdB was important
      for DTT- and NADH-dependent peroxidase activities in crude extracts, whereas the
      selenoperoxiredoxin PrxU could be depleted without affecting these peroxidase
      activities. GrdB could be heterologously produced in Escherichia coli with
      coexpression of selB and selC from E. acidaminophilum for selenocysteine
      insertion. Although GrdB was sensitive to proteolysis, some full-size protein was
      present which accounted for a peroxidase activity of about 0.5 U (mg protein)(-1)
      in these extracts. Mutation of the potentially redox-active UxxCxxC motif in GrdB
      resulted in still significant, but decreased activity. Heterologous GrdB was
      protected from degradation by full-length GrdE or by GrdE-domains. The GrdB-GrdE
      interaction was confirmed by copurification of GrdE with Strep-tagged GrdB. The
      data suggest that GrdE domains serve to stabilise GrdB.

PMID- 17009023
TI  - Relationships among the biosyntheses of ubiquinone, carotene, sterols, and
      triacylglycerols in Zygomycetes.
AB  - The Zygomycetes Phycomyces blakesleeanus and Blakeslea trispora are actual or
      potential sources of beta-carotene, ergosterol, ubiquinone, edible oil, and other
      compounds. By feeding [14C]acetyl-CoA, L-[14C]leucine, or R-[14C]mevalonate in
      the presence of excess unlabeled glucose, we found that ubiquinone (the terpenoid
      moiety), beta-carotene, and triacylglycerols were made from separate pools of all
      their common intermediates; the pools for ubiquinone and ergosterol were
      indistinguishable. Fatty acids were not labeled from mevalonate, showing the
      absence in these fungi of a shunt pathway that would recycle carbon from
      mevalonate and its products back to central metabolism. The overproduction of
      carotene in a Phycomyces mutant and in sexually mated cultures of Blakeslea
      modified the relative use of labeled and unlabeled carbon sources in the
      production of carotene, but not of the other compounds. We concluded that
      carotene, ubiquinone, and triacylglycerols are synthesized in separate
      subcellular compartments, while sterols and ubiquinone are synthesized in the
      same compartments or in compartments that exchange precursors. Carotene
      biosynthesis was regulated specifically and not by flow diversion in a branched
      pathway.

PMID- 17009024
TI  - 3D CT-based cephalometric analysis: 3D cephalometric theoretical concept and
      software.
AB  - INTRODUCTION: We present an original three-dimensional cephalometric analysis
      based on a transformation of a classical two dimensional topological
      cephalometry. METHODS: To validate the three-dimensional cephalometric CT based
      concept we systematically compared the alignments of anatomic structures. We used
      digital lateral radiography to perform the classical two-dimensional
      cephalometry, and a three-dimensional CT surface model for the three-dimensional
      cephalometry. RESULTS: Diagnoses based on both two-dimensional and three
      dimensional analyses were adequate, but the three-dimensional analysis gave more
      information such as the possibility of comparing the right and left side of the
      skull. Also the anatomic structures were not superimposed which improved the
      visibility of the reference landmarks. CONCLUSION: We demonstrated that three
      dimensional analysis gives the same results as two-dimensional analysis using the
      same skull. We also present possible applications of the method.

PMID- 17009025
TI  - Acute subarachnoid hemorrhage: using 64-slice multidetector CT angiography to
      "triage" patients' treatment.
AB  - INTRODUCTION: To evaluate the clinical role of CT angiography (CTA) in patients
      with acute subarachnoid hemorrhage (SAH) for treatment decision-making. METHODS:
      Consecutive patients with acute SAH had CTA using a 64-slice scanner for initial
      clinical decision-making. Image processing included multiplanar volume
      reformatted (MPVR) maximum intensity projections (MIP) and 3D volume-rendered
      reconstructions. CTAs were used for (1) evaluating the cause of SAH, and (2)
      triaging aneurysm-bearing patients to the more appropriate management, either
      surgical clipping or endovascular coiling. CTA findings were confirmed by
      neurosurgical exploration or catheter angiography (digital subtraction
      angiography, DSA). Successful coiling provided evidence that triaging to
      endovascular treatment was correct. RESULTS: Included in the study were 73
      patients. CTA findings were confirmed by DSA or neurosurgical operation in 65
      patients, and of these 65, 47 had aneurysmal SAH, 3 had vasculitis, 1 had
      arterial dissection and 14 had no underlying arterial abnormality. The cause of
      SAH was detected with CTA in 62 out of the 65 patients (95.4%, sensitivity 94%,
      specificity 100%). CTA revealed the aneurysm in 46 of 47 patients (98%,
      sensitivity 98%, specificity 100%, positive predictive value 100%, negative
      predictive value 82.3%), 1 of 3 vasculitides and 1 of 1 dissection. Of the 46
      patients with aneurysm, 44 (95.7%) were referred for treatment based on CTA. In 2
      patients (2 of 46, 4.4%) CTA was not informative enough to choose treatment
      requiring DSA. Of the 44 patients, 27 (61.4%) were referred to endovascular
      treatment and successful coiling was achieved in 25 (25 of 27, 92.6%).
      CONCLUSION: CTA using a 64-slice scanner is an accurate tool for detecting and
      characterizing aneurysms in acute SAH. CTA is useful in the decision process
      whether to coil or clip an aneurysm.

PMID- 17009026
TI  - Outcome and complications of 540 microvascular free flaps: the Hamburg
      experience.
AB  - The aim of this study was to retrospectively analyze surgical outcome and
      complications of 540 free flap procedures performed at the Department of Oral and
      Maxillofacial Surgery of the University Medical Center Hamburg-Eppendorf during
      1987-2005. A total of 532 patients were reconstructed with 540 flaps: 32% were
      latissimus dorsi flaps, 23% were radial forearm flaps, 21% were iliac crest
      flaps, 10% were fibula flaps, 6% were jejunal flaps, and 8% were other flaps.
      Thrombosis of one of the vessels and hematoma were the most frequent causes of
      failure in microvascular free tissue transfer. A total free flap failure occurred
      in 34 (6.2%) and a partial flap failure in 42 (7.7%) patients. The most reliable
      flap in regard to survival was the radial forearm flap. The present study
      confirms that free flaps are extremely reliable in achieving successful
      reconstruction of the head and neck.

PMID- 17009027
TI  - 3D femoral neck anteversion measurements based on the posterior femoral plane in
      ORTHODOC system.
AB  - This study provides a robust measuring method of the femoral neck anteversion
      angle for use in a total hip replacement pre-planning program. The femora of 24
      patients (69.3 +/- 6.3 years old) were CT-scanned and converted into three
      dimensionally volume-rendered models in ORTHODOC (ISS Inc., CA, USA) which is the
      pre-planning software for ROBODOC surgery. The Mod.ISS method (the modified ISS
      method), designed by authors, measures the anteversion angle of the proximal-most
      femoral neck confluence on the plane perpendicular to the femoral mechanical
      axis. 3D FNC method proposed by the authors of the present study involves
      measurement of the anteversion angle of three-dimensional femoral neck center on
      a plane perpendicular to the posterior femoral plane and parallel to the
      posterior condylar axis. Here, we found that interobserver reproducibility was
      1.8 degrees (SD = 1.3) for the Mod.ISS method and 2.4 (SD = 1.9) for the proposed
      3D FNC method. The anteversion angle of the local femoral neck axis was measured
      as theta = 25.3(L/D) + [corrected] 5.4 in L/D = 0.1-0.6, where L/D is distance
      (L) from the proximal-most neck confluence along the femoral mechanical axis,
      normalized with respect to the diameter of the femoral head (D). At L/D = 0.5,
      the anteversion angle of the femoral neck axis was coincident with the average
      femoral neck anteversion determined by the 3D FNC method. We conclude that the 3D
      FNC method is a gold standard for measuring the femoral neck anteversion
      applicable during both pre-operative and post-operative stages, because its
      femoral neck center can be determined in three-dimensional space during both
      stages.

PMID- 17009028
TI  - The pharmacokinetic behavior of the photosensitizer meso-tetra-hydroxyphenyl
      chlorin in mice and men.
AB  - PURPOSE: Meso-tetra-hydroxyphenyl-chlorin (mTHPC) is a hydrophobic
      photosensitizer that binds to plasma lipoproteins after intravenous injection. In
      vitro experiments with human plasma have shown that mTHPC initially binds to an
      unknown protein and subsequently redistributes to lipoprotein fractions. It has
      been suggested that this might explain the unusual pharmacokinetic profile of
      mTHPC humans. In humans, unlike in rodents, reappearance of mTHPC has been
      reported, resulting in a second plasma peak after intravenous injection. However,
      previous studies analyzed only limited time points during the first 24 h after
      injection. Our aim was to determine the pharmacokinetics of mTHPC in detail, and
      to investigate whether the pharmacokinetic behavior of the drug is affected by
      binding of mTHPC to lipoproteins in vivo. METHODS: Plasma of cancer patients and
      mice, intravenously injected with mTHPC, was analyzed for total drug content and
      drug distribution over the lipoprotein fractions. RESULTS: Pharmacokinetic
      profiles of mTHPC in a group of human subjects showed that apparent steady state
      drug levels were maintained for at least 10 h. Closer examination of individual
      profiles showed that the initial (5 min) plasma drug levels were on average 86%
      of the maximal plasma concentration, which occurred at about 5 h after injection.
      In mice, however, plasma pharmacokinetics were described by a standard bi
      exponential decline of the drug concentration. The majority (>58%) of mTHPC
      injected into both BALB/c nude mice and patients initially bound to the HDL
      plasma fraction. We extended our study to ApoE -/- mice, with highly elevated
      lipoprotein levels, and SR-BI -/- mice, which are lacking the main clearance
      pathway for HDL associated cholesteryl esters, to take into account the
      differences between lipoprotein levels and clearance in mice and man. Although
      mTHPC distribution over the lipoproteins changed in these mice, pharmacokinetic
      profiles of mTHPC remained the same. CONCLUSIONS: We conclude that neither
      lipoprotein levels nor cholesterol metabolism affects the pharmacokinetics of
      mTHPC in plasma.

PMID- 17009029
TI  - Irinotecan-cisplatin interactions assessed in cell-based screening assays:
      cytotoxicity, drug accumulation and DNA adduct formation in an NSCLC cell line.
AB  - PURPOSE: The use of in vitro drug cytotoxicity assays for the assessment of drug
      drug interactions that lead to synergy may not take into account the many
      cellular determinants responsible for combination effects. Administration of the
      anticancer drug CPT-11, for example, is associated with rapid conversion of drug
      from its active lactone form to the inactive carboxylate form. Thus it is
      difficult to model, in vitro, the behavior of this drug when used as a single
      agent and when used in a combination setting, this factor may contribute to the
      interactions measured. Therefore, the objective of this study was to examine the
      influence of CPT-11 lactone ratio on the cellular accumulation of CPT-11 when
      used as a single agent and under conditions where it is used in combination with
      cisplatin. METHODS: A fixed ratio experimental design was used and drug ratios of
      CPT-11 and cisplatin were judged to be antagonistic, additive, or synergistic to
      the non-small cell lung cancer cell line, H460, on the basis of the median effect
      analysis methodology of Chou and Talalay. The influence of extracellular pH on
      CPT-11 accumulation was evaluated at pH 7.4 and pH 6.6 when the drug was added
      immediately to the cells or first pre-equilibrated at the indicated pH. These
      studies were completed in the presence and absence of cisplatin. RESULTS: When
      CPT-11 was added as a single agent to cells in pH = 7.4 media, the drug underwent
      hydrolysis to the carboxylate form; however, there was a rapid accumulation of
      the CPT-11 lactone form which peaked at 3,800 pmol/mg protein by 30 min and drops
      to 570 pmol/mg protein by 24 h. In pH = 6.6 media, accumulation of CPT-11 lactone
      was substantially lower over a 60 min timecourse; however, the cellular uptake
      measured at 24 h was comparable to that observed when the drug was added into pH
      7.4 media. When evaluating CPT-11 lactone accumulation in a combination setting
      with cisplatin no significant difference in either CPT-11 lactone accumulation or
      cisplatin accumulation was observed, suggesting that drug interactions that led
      to synergy were mechanistically based. Results are presented which suggest that
      when cisplatin and CPT-11 are used in combination, there was a significant
      prolongation of platinum association with DNA compared to results obtained when
      cisplatin was used alone. CONCLUSION: These results suggest that the CPT-11
      lactone to carboxylate ratio does not influence the accumulation of the active
      CPT-11 lactone form in H460 cells and that CPT-11 does not influence cisplatin
      uptake when used in combination. It is argued, therefore, that the improved
      cytotoxicity between CPT-11 and cisplatin, as determined using cell-based assay,
      has the potential to be preserved in vivo assuming the optimal drug-drug ratio
      and concentration can be effectively delivered to the tumor.

PMID- 17009030
TI  - Dihydrodiol dehydrogenase in drug resistance and sensitivity of human carcinomas.
AB  - We previously reported (UroOncology 1:165, 2001) cross-resistance and collateral
      sensitivity to 2-chlorodeoxyadenosine (CldAdo) and fludarabine (FaraA),
      respectively, in a human renal cell carcinoma selected for resistance to 2'
      deoxytubercidin (Caki-dTub). Insofar that these drugs generally demonstrate cross
      resistance rather than collateral sensitivity, we further examined the bases for
      this phenomenon. Both CldAdo and FaraA induce apoptosis, as the triphosphates,
      via binding to Apaf-1. In the presence of cytochrome c, this binding leads to
      activation of procaspase 9 to active caspase 9 that induces apoptosis through its
      activation of caspase 3. CldAdo and FaraA induced caspase 3 activities in wild
      type and Caki-dTub cell lines in a dose-dependent manner that paralleled the
      cross-resistance (CldAdo, 200-fold) or collateral sensitivity (FaraA, 20-fold)
      with regard to cell viability. The activation of caspase 3 was inhibited by the
      caspase 9 inhibitor, Z-LEHD-FMK, suggesting that both drugs act via the same
      pathway. By differential display and direct enzyme analysis, dihydrodiol
      dehydrogenase (DDH) was observed to be profoundly underexpressed in the Caki-dTub
      compared to wild-type Caki-1 cells. Stable transfection of the Caki-dTub cells
      with a vector encoding the enzyme led to partial reversal of the resistance to
      CldAdo. Resistance to cisplatin has recently been ascribed to overexpression of
      DDH in a human ovarian carcinoma cell line (Deng et al. in J Biol Chem 227:15035,
      2002). It is tempting to speculate a mutation in the Apaf-1 nucleotide binding
      site that reduces (CldAdo) or increases (FaraA) toxicity in the Caki-dTub cells;
      however, the recent finding by others in a human ovarian carcinoma cell line
      suggests that DDH expression mediates the cross-resistance and perhaps,
      collateral-sensitivity.

PMID- 17009032
TI  - Phase II trial of 10-EDAM in the treatment of metastatic breast cancer.
AB  - INTRODUCTION: This phase II trial was conducted to assess the efficacy and safety
      of 10-Ethyl-10-Deaza-Aminopterin (10-EDAM), a folate antagonist, in metastatic
      breast cancer patients who had received no more than one prior chemotherapy
      regimen. METHODS: Fifty-five patients were treated on an initial weekly dose 80
      mg/m(2) of 10-EDAM. Patients who had received a prior chemotherapy regimen in the
      adjuvant setting (group 1) were considered separately from patients who had
      received a prior chemotherapy regimen in the metastatic setting (group 2).
      RESULTS: The response rate for both groups combined was 18%, and median time to
      progression was 3 months. Median overall survival was 12 months. Treatment was
      associated with common chemotherapy-related toxicities, such as 25% grade three
      or four neutropenia and 20% grade three or four stomatitis. CONCLUSION: In
      patients with metastatic breast cancer who had received one prior chemotherapy
      regimen, 10-EDAM was well tolerated. In general, while definite antitumor
      activity was documented, time to progression was brief.

PMID- 17009031
TI  - Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal
      cancer cells.
AB  - PURPOSE: Panax notoginseng is a commonly used Chinese herb. Although a few
      studies have found that notoginseng shows anti-tumor effects, the effect of this
      herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU)
      is a chemotherapeutic agent for the treatment of colorectal cancer that
      interferes with the growth of cancer cells. However, this compound has serious
      side effects at high doses. In this study, using HCT-116 human colorectal cancer
      cell line, we investigated the possible synergistic anti-cancer effects between
      notoginseng flower extract (NGF) and 5-FU on colon cancer cells. METHODS: The
      anti-proliferation activity of these modes of treatment was evaluated by MTS cell
      proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258
      staining and Annexin-V/PI staining assays. The anti-proliferation effects of four
      major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also
      analyzed. RESULTS: Both 5-FU and NGF inhibited proliferation of HCT-116 cells.
      With increasing doses of 5-FU, the anti-proliferation effect was slowly
      increased. The combined usage of 5-FU 5 microM and NGF 0.25 mg/ml, significantly
      increased the anti-proliferation effect (59.4 +/- 3.3%) compared with using the
      two medicines separately (5-FU 5 microM, 31.1 +/- 0.4%; NGF 0.25 mg/ml, 25.3 +/-
      3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert
      an apoptotic effect, while apoptotic cells induced by NGF were observed,
      suggesting that the anti-proliferation target(s) of NGF may be different from
      that of 5-FU, which is known to inhibit thymidilate synthase. CONCLUSIONS: This
      study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on
      HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed
      for colorectal cancer treatment.

PMID- 17009033
TI  - A phase II trial of continuous low-dose oral cyclophosphamide and celecoxib in
      patients with renal cell carcinoma.
AB  - PURPOSE: The lack of effective systemic therapies for patients with advanced
      renal cell carcinoma (RCC) has stimulated interest in evaluating novel treatment
      strategies for this disease. METHODS: This was a two-institution, two-stage,
      phase II trial of continuous low-dose oral cyclophosphamide (50 mg daily) in
      combination with celecoxib (400 mg twice daily) in patients with progressive,
      locally advanced or metastatic RCC. The primary endpoint was disease control rate
      (DCR) defined as the number of patients with complete (CR) or partial response
      (PR) or prolonged (> or =6 months) stable disease (SD). Secondary endpoints
      included time to progression and toxicity. RESULTS: Between May 2001 and January
      2003, 36 patients were enrolled onto the trial of which 32 were evaluable for
      response. One patient had a PR and three others had SD for longer than 6 months
      (DCR 12.5%, 95% CI 3.5-29.0%). The median progression free survival was 3.5
      months (95% CI, 1.9-4.1 months) and the median overall survival was 14.5 months
      (95% CI, 8.4-20.8 months). One patient experienced grade five gastrointestinal
      bleeding. Otherwise, the treatment was well tolerated. CONCLUSIONS: Although
      generally well tolerated, continuous therapy with low-dose cyclophosphamide and
      celecoxib had limited activity in RCC.

PMID- 17009034
TI  - A triplet chemotherapy with cisplatin, docetaxel and gemcitabine in patients with
      advanced non-small-cell lung cancer: a phase I/II study.
AB  - PURPOSE: We conducted a phase I/II study of triplet chemotherapy consisting of
      cisplatin (CDDP), docetaxel (DCT) and gemcitabine (GEM) in patients with advanced
      non-small-cell lung cancer (NSCLC). METHODS: Fifty-three untreated patients with
      stage IIIB or IV NSCLC were enrolled. All drugs were given on days 1 and 8. The
      doses of CDDP and DCT were fixed at 40 mg/m(2) and 30 mg/m(2), respectively. In
      the phase I portion, a dose escalation study of GEM with starting dose of 400
      mg/m(2) was conducted and primary objective in the phase II portion was response
      rate. RESULTS: The maximally tolerated dose (MTD) and recommended dose (RD) of
      GEM were determined as 800 mg/m(2) because grade 3 non-hematological toxicity
      (liver damage, diarrhea, and fatigue) developed in three of nine patients
      evaluated at that dose level. In pharmacokinetic analysis, C (max) and AUC of
      dFdC and dFdU were increased along with the dose escalation of GEM. However, no
      relationship between pharmacokinetic parameters and toxicity or response was
      observed. Objective response rate was 34% and median survival time was 11.7
      months. Though major toxicity was myelosuppression, there were no life
      threatening toxicities. CONCLUSION: These results indicate that this triplet
      chemotherapy is feasible and effective in patients with advanced NSCLC.

PMID- 17009035
TI  - Capecitabine improves cancer cachexia and normalizes IL-6 and PTHrP levels in
      mouse cancer cachexia models.
AB  - PURPOSE: To clarify the potential of parathyroid hormone-related protein (PTHrP)
      and interleukin-6 (IL-6) as cachectic factors in a colon 26 model and the effects
      of capecitabine on cancer cachexia as determined by plasma levels of IL-6 and
      PTHrP and body weight loss. METHODS: From two colon 26 sublines-cancer cachectic
      clone20 and non-cachectic clone5 plasma levels of PTHrP protein and mRNA
      expression levels in tumor tissues were compared. An IL-6 neutralizing antibody,
      a PTHrP neutralizing antibody, and capecitabine were administered into mice
      bearing clone20 and their anticachectic effects evaluated. RESULTS: The plasma
      level of PTHrP protein in mice bearing clone20 was higher than that in mice
      bearing clone5. The expression level of PTHrP mRNA was 49-fold higher in tumor
      tissues of clone20 than of clone5, according to GeneChip analysis. PTHrP antibody
      as well as IL-6 antibody suppressed wasting of the body and gastrocnemius and
      adipose tissue weights. PTHrP antibody suppressed the induction of hypercalcemia
      but not hypoglycemia or elevation of IL-6, whereas IL-6 antibody suppressed the
      induction of hypoglycemia but not hypercalcemia or elevation of PTHrP.
      Capecitabine, a fluorinated pyrimidine anticancer agent, improved body wasting of
      mice bearing clone20 at a low dose with no reduction of tumor volume.
      Furthermore, capecitabine lowered the levels of PTHrP and IL-6 in plasma and
      suppressed hypoglycemia and hypercalcemia in this model. Capecitabine also showed
      anticachectic effects on cachexia in a cancer model induced by human cervical
      cancer cell line Y (also known as Yumoto). CONCLUSIONS: PTHrP and IL-6 were found
      to be factors in the development of cachexia in a colon 26 cancer model, and
      capecitabine improved cancer cachexia by suppressing the plasma levels of IL-6
      and PTHrP in colon 26 and Y cachectic models.

PMID- 17009036
TI  - TEXAS (Taxotere EXperience with Anthracyclines Study) trial: mature results of
      activity/toxicity of docetaxel given with anthracyclines in a community setting,
      as first line therapy for MBC.
AB  - PURPOSE: The TEXAS (Taxotere EXperience with Anthracyclines Study) study examined
      docetaxel in combination with an anthracycline, as first line treatment of
      metastatic breast cancer (MBC), in everyday practice, and compared the findings
      with a randomised controlled trial. METHODS: Four hundred and seventy patients
      were registered on the TEXAS trial. Patients were assigned, according to treating
      clinician's discretion, to either doxorubicin 50 mg/m2 or epirubicin 75 mg/m2
      both given day1 15 min intravenous bolus every 3 weeks, followed by docetaxel 75
      mg/m2, day 1, 1 h intravenous infusion every 3 weeks. RESULTS: The overall
      response rate (ORR) was approximately 61%. The main toxicity reported was
      neutropenia, with 75 patients (55%) in the AT group and 203 (61%) in the ET arm.
      Febrile neutropenia or neutropenic sepsis was reported for 32 (24%) of the AT arm
      and 78 (23%) of the ET arm. CONCLUSIONS: This open access study demonstrates that
      AT or ET are highly active treatments for MBC, with similar response rates to
      those observed in a phase III clinical trial. This may be important for patients
      with rapidly progressive visceral disease. Side effects can be managed
      effectively with growth factors and/or prophylactic antibiotic.

PMID- 17009037
TI  - cDNA microarray study to identify expression changes relevant for apoptosis in
      K562 cells co-treated with amifostine and imatinib.
AB  - PURPOSE: Chronic myeloid leukemia is a clonal myeloproliferative disorder
      characterized by the presence of the fusion gene BCR/ABL. We had previously
      demonstrated an increased proapoptotic effect of imatinib (STI571) in combination
      with amifostine (AMI) in K562 cell line. In this study, we used genomic scale
      gene expression profiling to monitor changes at transcriptional level in K562
      cells during the treatment with AMI + STI571. MATERIALS AND METHODS: cRNA from
      Control and treated K562 cells were mixed in equal amounts and incubated with a
      microarray slide for hybridization. RNA from six independent paired experiments
      was subjected to transcriptional profiling. With the aim to automate the process
      of biological theme determination, selected genes were further analyzed by EASE.
      Validation of the expression was carried out by quantitative real-time PCR and
      western blotting. RESULTS: As expected, a small percentage of genes accounts for
      the effects of the combined drug treatment. We identified 61 sequences
      corresponding to known genes; 17 of the 61 genes were up regulated, such as RHO6,
      PPP2R5E, PPM1E and BTF that appear to reflect favorable events for apoptosis
      induction. Between down regulated genes, API5, TUBB2 and TLK1 are also of
      considerable interest. CONCLUSION: We identified a transcriptional repressor of
      survival genes, known as BTF, which triggers a proapoptotic signal, potentially
      helpful to overcome the resistance to STI571. This finding could be particularly
      useful to design novel therapeutic strategies for leukemia patients. This study
      demonstrates the importance of in vitro testing of a novel drug combination most
      likely to predict its potential usefulness for in vivo application.

PMID- 17009039
TI  - [Volume and electrolyte disturbances in endurance sport].
AB  - Long-lasting endurance exercise is associated with significant losses of fluid
      and sodium chloride, mainly due to sweat loss. To maintain endurance capacity and
      to avoid negative health consequences, endurance athletes should, therefore,
      drink fluids containing electrolytes during and after training or competition. In
      long-lasting endurance exercise it is recommended that athletes drink about 600
      800 ml/h of fluid including adequate substitution of sodium. The excessive
      ingestion of fluid, however, brings about a danger of hyponatremia, which can be
      avoided by suitable measures. Body weight control is one of the parameters that
      should be carefully monitored before and after intensive endurance exercise.

PMID- 17009040
TI  - [Antiviral therapy: from influenza to Pfeiffer's disease].
AB  - Antiviral drug therapy has rapidly evolved in recent years. A large number of
      specific inhibitors against newly detected viral targets has been developed.
      Viral infections except HIV and viral hepatitis infections are clinically
      relevant mostly in severely immunocompromised patients. Especially respiratory
      viral infections and herpes virus infections are associated with high morbidity
      and mortality in these patients. Therapeutic and preventive strategies have been
      developed for a number of these infections. There is high priority for the
      development of new substances for a number of viruses not yet treatable and
      substances active against resistant viral strains.

PMID- 17009041
TI  - [Volume retention in heart failure, nephrotic syndrome, and liver cirrhosis].
AB  - Volume retention in heart failure, nephrotic syndrome, and liver cirrhosis
      reflects pathological changes in homeostatic mechanisms that regulate the
      extracellular volume (sympathetic activity, renin-angiotensin-aldosterone system
      [RAAS], natriuretic peptides) and plasma osmolality (antidiuretic hormone [ADH]).
      In heart failure and liver cirrhosis, these changes are induced by a reduction of
      the effective circulating volume, which is the part of the extracellular fluid
      that is within the arterial system and effectively perfusing the tissues. This
      reduction in the effective circulating volume is caused by reduced cardiac output
      (heart failure), or by splanchnic vasodilatation with arterial underfilling
      (liver cirrhosis). In both cases, baroreceptors in both the carotid sinuses and
      in the glomerular afferent arterioles upregulate RAAS- and sympathetic activity,
      resulting in systemic vasoconstriction and renal sodium (and volume) retention.
      More severe reductions in the effective circulating volume may additionally
      stimulate ADH release, thus increasing the reabsorption of free water with
      subsequent hyponatriemia. In nephrotic syndrome, volume retention results either
      directly from the primary renal disease, which induces renal sodium and volume
      retention ("overfilling"), or indirectly from the reduced plasma oncotic pressure
      due to hypoalbuminemia, which induces a fluid shift from the intravascular to the
      interstitial space ("underfilling") with subsequent acitivation of baroreceptors
      and secondary sodium and volume retention.

PMID- 17009042
TI  - [Disturbances in volume and electrolytes with intestinal and kidney diseases].
AB  - The intestines and kidney are the most important excretion organs. Both organ
      systems are key players in keeping the homeostatic balance regarding hydration
      and electrolytes. Disturbances of function can lead to enormous and sometimes
      life-threatening complications. Intestinal diseases lead often to diarrhoea,
      which can be associated with fluid loss of up to 20 l per day. The accompanying
      electrolyte disturbances can be hypo- or hypernatremia in combination with
      hypokalemia. The therapy is substitution guided by knowledge of the
      pathophysiology. Kidney diseases lead to excessive volume and electrolyte
      balances, depending on the underlying molecular or pathological defect, but
      deficiencies can also be found. In case of kidney impairment with 30-50% total
      loss of function, calcium and phosphate metabolism is impaired.

PMID- 17009044
TI  - Immunization of Rhesus monkeys with a SialylTn-mAb17-1A conjugate vaccine co
      formulated with QS-21 induces a temporary systemic cytokine release and NK
      cytotoxicity against tumor cells.
AB  - Tumor-associated antigens resulting from aberrant glycosylation, such as the
      SialylTn carbohydrate antigen, are frequently over-expressed on cancer cells and
      provide potential targets for cancer vaccination. Immunization of Rhesus monkeys
      with SialylTn coupled to a highly immunogenic carrier molecule and formulated on
      aluminum hydroxide induced a strong immune response against the carrier protein
      but only a moderate IgM immune response against the SialylTn carbohydrate
      antigen. Co-formulation with QS-21 adjuvant dramatically enhanced the anti
      SialylTn immune response and resulted in a SialylTn-specific IgG switch. The
      kinetics of the carbohydrate-specific IgG response correlated with a temporary
      release of cytokines such as IFNgamma, IL-2, IL-1beta, TNFalpha and GM-CSF which
      was measurable in the immune serum by xMAP Multiplex technology. Furthermore,
      tumor cell killing by activated natural killer cells was induced. These data
      demonstrate that immunization with a tumor-associated carbohydrate antigen in a
      highly immunogenic formulation results in a temporary release of type 1 cytokines
      which may be required for the induction of a specific IgG immune response against
      the carbohydrate antigen as well as for activation of effector cells against
      tumor cells.

PMID- 17009043
TI  - Imatinib impairs CD8+ T lymphocytes specifically directed against the leukemia
      associated antigen RHAMM/CD168 in vitro.
AB  - The Bcr-Abl tyrosine kinase inhibitor imatinib mesylate is highly effective in
      the front-line treatment of chronic myeloid leukemia (CML) and is increasingly
      used in patients with residual disease or relapse after allogeneic stem cell
      transplantation (allo-SCT). Since an impairment of anti-viral CD8+ T-lymphocyte
      function by imatinib has been described, we question whether imatinib also
      affects specific anti-leukemic CD8+ T lymphocytes generated from the peripheral
      blood of healthy donors, and of CML patients after allo-SCT. Here, we assessed
      CD8+ T-cell expansion and function from healthy donors and patients with CML. The
      release of IFN-gamma and granzyme B by CD8+ T-lymphocytes specific for R3, a
      recently described T-cell epitope peptide derived from a leukemia-associated
      antigen designated RHAMM/CD168 (receptor for hyaluronic acid mediated motility),
      was inhibited by imatinib in a dose-dependent fashion (range: 1-25 microM). These
      T cells were able to lyse cognate peptide labeled T2 cells and CD34+ CML
      progenitor cells. This lysis was inhibited by imatinib. The inhibitory effect was
      not associated with an increased rate of apoptosis of T cells and reversible
      after removal of imatinib. In the light of these findings, clinical
      administration of imatinib might result in the reduction of efficacy of the graft
      versus-leukemia effect or other T-cell-based immunotherapies.

PMID- 17009045
TI  - Expanding the body mass range: associations between BMR and tissue morphology in
      wild type and mutant dwarf mice (David mice).
AB  - We sought to identify associations of basal metabolic rate (BMR) with
      morphological traits in laboratory mice. In order to expand the body mass (BM)
      range at the intra-strain level, and to minimize relevant genetic variation, we
      used male and female wild type mice (C3HeB/FeJ) and previously unpublished ENU
      induced dwarf mutant littermates (David mice), covering a body mass range from
      13.5 g through 32.3 g. BMR was measured at 30 degrees C, mice were killed by
      means of CO(2 )overdose, and body composition (fat mass and lean mass) was
      subsequently analyzed by dual X-ray absorptiometry (DEXA), after which mice were
      dissected into 12 (males) and 10 (females) components, respectively. Across the
      44 individuals, 43% of the variation in the basal rates of metabolism was
      associated with BM. The latter explained 47% to 98% of the variability in
      morphology of the different tissues. Our results demonstrate that sex is a major
      determinant of body composition and BMR in mice: when adjusted for BM, females
      contained many larger organs, more fat mass, and less lean mass compared to
      males. This could be associated with a higher mass adjusted BMR in females. Once
      the dominant effects of sex and BM on BMR and tissue mass were removed, and after
      accounting for multiple comparisons, no further significant association between
      individual variation in BMR and tissue mass emerged.

PMID- 17009046
TI  - Stimulus and response repetition effects in the detection of sounds: evidence of
      obligatory retrieval and use of a prior event.
AB  - Three experiments were performed to examine the extent to which the time required
      to detect a probe sound is determined by the acoustic characteristics of a
      preceding prime sound and by the nature of the response made to the prime. The
      results of Experiment 1 revealed that the effect of frequency repetition was
      facilitative when a response was made to the occurrence of both the prime and the
      probe, but was inhibitory when a response was made only to the probe. In
      contrast, there was no significant effect of location repetition when responses
      were made to both prime and probe but there was a strongly inhibitory effect when
      a response was required only to the probe. These results suggest that the
      acoustic characteristics of the prime along with information about any response
      made to it, are used in preparing and executing a response to the probe.
      Experiment 2 was designed to disrupt the temporal link between prime and probe as
      a way to discourage such retrieval. The results of the experiment revealed that
      although a response was required to both the prime and probe, no significant
      effect of frequency repetition was apparent but a robust inhibitory effect of
      location repetition emerged. In the third experiment repetition effects both
      within a trial (i.e., prime to probe) and between trials (i.e., probe to prime)
      were examined. A facilitative effect of frequency repetition was apparent when
      the interval between sounds was brief, and an inhibitory effect of location
      repetition was apparent when the interval between sounds was relatively lengthy.
      Taken together these results suggest that even simple perceptual judgments may be
      influenced by retrieval of information about a previous processing episode and
      that effects of frequency repetition and location repetition may be mediated by
      different mechanisms.

PMID- 17009047
TI  - Extrapolating from animal studies to the efficacy in humans of a pretreatment
      combination against organophosphate poisoning.
AB  - The extrapolation from animal data to therapeutic effects in humans, a basic
      pharmacological issue, is especially critical in studies aimed to estimate the
      protective efficacy of drugs against nerve agent poisoning. Such efficacy can
      only be predicted by extrapolation of data from animal studies to humans. In
      pretreatment therapy against nerve agents, careful dose determination is even
      more crucial than in antidotal therapy, since excessive doses may lead to adverse
      effects or performance decrements. The common method of comparing dose per body
      weight, still used in some studies, may lead to erroneous extrapolation. A
      different approach is based on the comparison of plasma concentrations at steady
      state required to obtain a given pharmacodynamic endpoint. In the present study,
      this approach was applied to predict the prophylactic efficacy of the
      anticholinergic drug caramiphen in combination with pyridostigmine in man based
      on animal data. In two species of large animals, dogs and monkeys, similar plasma
      concentrations of caramiphen (in the range of 60-100 ng/ml) conferred adequate
      protection against exposure to a lethal-dose of sarin (1.6-1.8 LD(50)).
      Pharmacokinetic studies at steady state were required to achieve the correlation
      between caramiphen plasma concentrations and therapeutic effects. Evaluation of
      total plasma clearance values was instrumental in establishing desirable plasma
      concentrations and minimizing the number of animals used in the study. Previous
      data in the literature for plasma levels of caramiphen that do not lead to overt
      side effects in humans (70-100 ng/ml) enabled extrapolation to expected human
      protection. The method can be applied to other drugs and other clinical
      situations, in which human studies are impossible due to ethical considerations.
      When similar dose response curves are obtained in at least two animal models, the
      extrapolation to expected therapeutic effects in humans might be considered more
      reliable.

PMID- 17009048
TI  - Sodium arsenite-induced inhibition of cell proliferation is related to inhibition
      of IL-2 mRNA expression in mouse activated T cells.
AB  - A proposed mechanism for the As-induced inhibition of cell proliferation is the
      inhibition of IL-2 secretion. However, the effects of arsenite on IL-2 mRNA
      expression or on the ERK pathway in activated-T cells have not yet been
      described. We examined the effect of arsenite on IL-2 mRNA expression, cell
      activation and proliferation in PHA-stimulated murine lymphocytes. Arsenite (1
      and 10 microM) decreased IL-2 mRNA expression, IL-2 secretion and cell
      proliferation. Arsenite (10 microM) strongly inhibited ERK-phosphorylation.
      However, the partial inhibition (50%) of IL-2 mRNA produced by 1 microM,
      consistent with the effects on IL-2 secretion and cell proliferation, could not
      be explained by the inhibition of ERK-phosphorylation, which was not affected at
      this concentration. The inhibition of IL-2 mRNA expression caused by 1 microM
      could be associated to effects on pathways located downstream or parallel to ERK.
      Arsenite also decreased early activation (surface CD69+ expression) in both CD4+
      and CD8+, and decreased total CD8+ count without significantly affecting CD4+,
      supporting that the cellular immune response mediated by cytotoxic T cells is an
      arsenic target. Thus, our results suggest that arsenite decreases IL-2 mRNA
      levels and T-cell activation and proliferation. However, further studies on the
      effects of arsenite on IL-2 gene transcription and IL-2 mRNA stability are
      needed.

PMID- 17009049
TI  - [Stroke].
AB  - Today stroke represents a major medical and political problem in Western
      industrial nations. High demands need to be placed on the initial diagnostic work
      up and therapeutic treatment to ensure that the patients benefit from the recent
      advancements achieved in diagnostic and therapeutic fields. According to the
      motto "time is brain" the clinical examination and imaging have to be performed
      within 60 min ("door to needle time") so that potential patients can be quickly
      treated with systemic or intra-arterial lysis. However, it should be taken into
      consideration that the selection of diagnostic imaging facilities depends on
      several factors such as infrastructure, the time remaining in the diagnostic
      window, and the severity of the clinical symptoms.

PMID- 17009050
TI  - Staged based directed surveillance of invasive bladder cancer following radical
      cystectomy: valuable and effective?

PMID- 17009051
TI  - Improving outcomes with radical cystectomy for high-grade invasive bladder
      cancer.
AB  - It is clear that the optimal clinical outcomes in bladder cancer patients
      requiring radical cystectomy are related to standard histopathologic variables of
      tumor grade, stage and lymph node status. However, other less well defined
      variables are also critical to the successful outcomes of these patients.
      Patients with muscle invasive bladder cancer and treating physicians should avoid
      unnecessary and significant treatment delays. In addition, hospital and surgeon
      volume/experience are thought to be factors that may too be important components
      that relate to the clinical outcomes of patients following surgery. Lastly, there
      is a growing body of literature to support the concept of an appropriate
      lymphadenectomy at the time of surgery, for both node-positive and node-negative
      bladder cancer patients. It is becoming more obvious that there are multiple
      variables involved in the clinical success and outcomes of patients with bladder
      cancer following radical cystectomy. As treating physicians and surgeons we must
      be aware of these components to ensure the best outcomes for our patients.

PMID- 17009052
TI  - Physiological changes of premotor nonspiking interneurons in the central
      compensation of eyestalk posture following unilateral sensory ablation in
      crayfish.
AB  - We investigated how the physiological characteristics and synaptic activities of
      nonspiking giant interneurons (NGIs), which integrate sensory inputs in the brain
      and send synaptic outputs to oculomotor neurons innervating eyestalk muscles,
      changed after unilateral ablation of the statocyst in order to clarify neuronal
      mechanisms underlying the central compensation process in crayfish. The input
      resistance and membrane time constant in recovered animals that restored the
      original symmetrical eyestalk posture 2 weeks after operation were significantly
      greater than those immediately after operation on the operated side whereas in
      non-recovered animals only the membrane time constant showed a significant
      increase. On the intact side, both recovered and non-recovered animals showed no
      difference. The frequency of synaptic activity showed a complex pattern of change
      on both sides depending on the polarity of the synaptic potential. The synaptic
      activity returned to the bilaterally symmetrical level in recovered animals while
      bilateral asymmetry remained in non-recovered ones. These results suggest that
      the central compensation of eyestalk posture following unilateral impairment of
      the statocyst is subserved by not only changes in the physiological
      characteristics of the NGI membrane but also the activity of neuronal circuits
      presynaptic to NGIs.

PMID- 17009056
TI  - Ultraviolet A1 phototherapy decreases inhibitory SMAD7 gene expression in
      localized scleroderma.
AB  - Localized scleroderma (LS) is a connective skin disease with marked sclerosis of
      the skin as the most prominent feature. Transforming growth factor beta (TGF
      beta) plays a central role in the pathogenesis of sclerotic skin diseases.
      Recently, special attention was contributed to a family of transcription factor
      proteins involved in TGF-beta signal transduction from cell surface to the
      nucleus, the so-called SMADs. Ultraviolet (UV) irradiation has been reported to
      alter TGF-beta/SMAD pathway in human skin. We sought to investigate the effects
      of UVA1 on the gene and protein expressions of the TGF-beta/SMAD pathway in LS.
      UVA1 phototherapy was performed in eight LS patients five times weekly for 8
      weeks resulting in a total of 40 treatment sessions (single dose 50 J/cm(2),
      cumulative dose 2,000 J/cm(2)). TGF-beta1, SMAD3, SMAD4, and SMAD7 mRNA
      expressions were determined by semiquantitative real-time reverse transcription
      polymerase chain reaction in lesional and unaffected skin of patients with LS.
      Additionally, immunohistochemical staining was performed in lesional skin before
      and after irradiation. Skin status markedly improved in all patients, resulting
      in a significant reduction of the clinical score from baseline to the end of
      treatment. Inhibitory SMAD7 mRNA was significantly higher in lesional skin as
      compared to unaffected skin, and significantly decreased after UVA1 phototherapy.
      In contrast, SMAD7 mRNA levels remained unchanged in irradiated, healthy skin
      after UVA1. Both TGF-beta and SMAD3 mRNA levels decreased after UVA1, whereas
      SMAD4 mRNA increased. However, changes in TGF-beta, SMAD3, and SMAD4 mRNA after
      UVA1 did not reach statistical significance. Immunohistochemical investigation
      did not reveal significant changes in the protein expression of SMADs after UVA1.
      Similar to scleroderma, SMAD7-mediated negative regulation seems to be impaired
      in LS. UVA1 phototherapy demonstrated the alteration of SMAD7 gene expression in
      LS, as SMAD7 mRNA levels normalized after UVA1. The pathogenetic relevance of
      SMAD7 levels with respect to clinical improvement needs further investigation.

PMID- 17009057
TI  - [Exercise training for the prevention and treatment of lifestyle-induced
      diseases].
AB  - Diabetes mellitus is one of the major risk factors for coronary artery disease,
      which progresses in diabetics at a faster rate and is associated with a worse
      prognosis. Although interventional or surgical revascularization provide quick
      relief of symptoms for patients with stable coronary artery disease it has
      limited prognostic benefit. A multi-factorial intervention, which includes
      dietary measures, glucose and lipid control, anti-hypertensive treatment, and
      regular physical exercise does exert a positive impact on modifiable risk
      factors, improves cardiovascular fitness, angina-free exercise tolerance and is
      associated with a better prognosis. Neither our patients, nor us physicians or
      even our societies can afford not to include physical exercise into every persons
      daily life.

PMID- 17009060
TI  - [Cocaine addiction: the therapeutic challenge by diversified addiction pattern].

PMID- 17009061
TI  - Biological therapies: concepts and challenges.

PMID- 17009062
TI  - Public health aspects of diabetes mellitus--epidemiology, prevention strategies,
      policy implications: the first Austrian diabetes report.

PMID- 17009063
TI  - Takotsubo cardiomyopathy in positron emission tomography.

PMID- 17009064
TI  - [Cocaine abuse in Vienna and European cities--a multi-center study].
AB  - INTRODUCTION: As cocaine consumption seems to have increased over the last
      decades, the EU has funded this multi-center, cross-sectional survey to
      investigate cocaine consumption in three different target groups. The study was
      conducted by the Addiction Clinic, Department of Psychiatry, Medical University
      Vienna and other nine European cities. METHODS: Data were collected by structured
      face-to-face interviews. The sample was composed of 211 cocaine abusers out of
      three target groups: (1) treatment group undergoing opioid maintenance therapy,
      (2) marginalized scene group and (3) integrated party group. Sociodemographic
      data such as age, education, employment, monthly expenses on cocaine/crack, data
      on consumption patterns, physical and mental health and personal needs regarding
      cocaine consumption were evaluated. Urine toxicology results for cocaine in the
      treatment group completed the analysis. RESULTS: The marginalized scene group was
      the oldest with a mean age of 29.35 years, with the highest unemployment rate
      (mean 25.11 days) and the longest duration of cocaine consumption (mean 5.80
      years). They had the highest cocaine consumption pattern with a mean of 22.32
      days within the last month. On average 1969 Euros/months was spent for their
      addiction. The treatment group had the lowest school education with a mean of
      10.36 years, but showed a sufficient insight in their cocaine problem. However,
      the party group (with the lowest mean age, 25.64 years) highly underestimated
      their drug problem, the mean amount of money they spent for their addiction was
      588.99 Euro/months. Structured urine toxicology between 1996 and 2002 in patients
      undergoing opioid maintenance therapy ("treatment group") revealed a significant
      increase of concomitant cocaine consumption (1996: 33.1%; 2002: 40.2%; p =
      0.044). DISCUSSION: The European trend of increased cocaine use could also be
      observed in Vienna. One of the greatest barriers for establishing adequate
      treatment settings for this target group is the difficulty to reach this
      population. In addition, multiple substance abuse seems to be one of the
      predominating patterns of cocaine consumption and this aspect should be
      integrated within treatment (in the treatment and scene groups additional heroin
      and benzodiapzepines abuse is observed, in the party group intensive alcohol
      consumption). The Viennese results are in line with those of the other European
      cities; however, it could not be confirmed that consumption of crack cocaine and
      binge play a similarly significant role as in cities such as Hamburg or London.

PMID- 17009065
TI  - Clinical appearance of erythema migrans caused by Borrelia afzelii and Borrelia
      garinii--effect of the patient's sex.
AB  - AIM: The aim in this survey was to study the clinical characteristics of
      infections caused by Borrelia genospecies in patients with erythema migrans where
      borrelial origin was confirmed by polymerase chain reaction. The aim was also to
      study factors influencing the clinical appearance of erythema migrans. METHODS:
      The study was conducted in southern Sweden from May 2001 to December 2003 on
      patients 18 years and older attending with erythema migrans at outpatient
      clinics. All erythema migrans were verified by polymerase chain reaction,
      photographed and categorized as "annular" or "non-annular" lesions. A logistic
      regression model was used to analyze relations between the appearance of the
      erythema migrans (i.e. annular or non-annular) and factors that influenced its
      clinical appearance. RESULTS: A total of 118 patients, 54 women (45.8%) and 64
      men (54.2%), fulfilled the inclusion criteria. Of these patients, 74% were
      infected by B. afzelii and 26% by B. garinii (p < 0.001). A total of 45% (38/85)
      of the erythema migrans were annular, 46% (39/85) were nonannular and 9.4% (8/85)
      were atypical. For men infected by B. afzelii, the odds ratio of developing non
      annular erythema migrans was 0.09 (95% CI: 0.03-0.33) in comparison with women
      with the same infection. CONCLUSIONS: In this prospective study of a large series
      of erythema migrans, where infecting genospecies were confirmed by polymerase
      chain reaction, the sex of patients infected with B. afzelii had a strong
      influence on the appearance of the rash. Patients infected by B. garinii more
      often had non-annular erythema migrans and a more virulent infection with more
      individuals presenting with fever, raised levels of C-reactive protein and
      seroreactivity in the convalescence sera.

PMID- 17009066
TI  - Echocardiographic findings in patients with Williams-Beuren syndrome.
AB  - BACKGROUND: Williams-Beuren syndrome is a multisystem developmental disorder
      caused by a microdeletion at chromosome 7q11.23. In its classic form it includes
      dysmorphic facial features, joint contractures, retardation of growth and mental
      development, gregarious personality, visuospatial cognitive deficits,
      hypercalcemia, primary or secondary hypertension and cardiovascular disorders.
      AIM: Clinical diagnosis of Williams-Beuren syndrome can be a challenge in young
      patients if none of the characteristic cardiovascular features, i.e.
      supravalvular aortic stenosis or pulmonary artery stenosis, are present. Our aim
      was to demonstrate the changes in cardiovascular lesions during the postnatal
      development of Williams-Beuren patients and to follow all cardiovascular findings
      beyond the most common ones. METHODS: The cardiovascular status of 29 patients
      with Williams-Beuren syndrome (mean age 12.8 years) was recorded in correlation
      with age. RESULTS: Cardiovascular diagnoses changed in the majority (72.4%) of
      patients. Interestingly, 44.8% of the patients had periods with no reported
      cardiovascular disease. Furthermore, 65.5% of the patients experienced periods
      when none of the typical cardiovascular lesions, i.e. diffuse or localized
      supravalvular aortic stenosis and/or pulmonary artery stenosis, were detected.
      Spontaneous regression and progression of both supravalvular aortic stenosis and
      pulmonary artery stenosis were observed. An unexpectedly high frequency (41%) of
      mitral valve disorders was found. CONCLUSIONS: Our study showed that temporary
      absence of and changes in cardiovascular findings are frequent in Williams-Beuren
      syndrome. These results could contribute to the refinement of diagnostic criteria
      and recommendations for cardiovascular follow-up of patients with this syndrome.

PMID- 17009067
TI  - Improvement of glycemic control after a 3-5 day insulin infusion in type 2
      diabetic patients with insulin resistance can be maintained with glitazone
      therapy.
AB  - INTRODUCTION: Insulin resistance is a common problem in obese patients with type
      2 diabetes. In a prospective randomized study, we investigated the improvement of
      metabolic control after a 3-5 day period of intravenous insulin infusion in
      poorly insulin-treated, overweight type 2-diabetic patients with and without
      additional glitazone therapy. METHODS: Twenty-eight overweight patients (BMI >
      28) with poorly insulin-treated type 2 diabetes (HbA1c > 8%) requiring > 80 IU
      insulin/day received a continuous insulin infusion for 3-5 days (initially 4-6 IU
      insulin/hour). Thereafter, 14 of the patients also received pioglitazone (15
      mg/day). The two groups were compared for HbA1c, mean blood glucose (MBG), body
      weight, cholesterol, triglycerides and insulin requirement (IU/day) three months
      before insulin infusion, during infusion, and at three and six months after the
      infusion. RESULTS: Glycemic control was immediately improved under insulin
      infusion in both groups: MBG was reduced from 188 +/- 32 mg/dl at baseline to 142
      +/- 28 mg/dl at the end of insulin infusion (p < 0.05). In the group receiving
      pioglitazone, the mean HbA1c three months after the insulin infusion was 16%
      lower and after six months 17% lower than baseline values (p < 0.02).
      Concomitantly, the required insulin dose decreased significantly by 15% after
      three months and 18% after six months (p < 0.02). Two patients (14%) were non
      responders (< 10% reduction of required insulin dose). In the group without
      pioglitazone the mean HbA1c level three months after insulin infusion was 10%
      lower (p < 0.05) than at baseline; at six months the HbA1c value was the same as
      that before the infusion. The required insulin dose was 10% lower after three
      months and only 3% lower after six months (NS). Four patients (28%) were non
      responders. DISCUSSION: Short-term insulin infusion therapy is effective in
      improving metabolic control and, concomitantly, in reducing insulin requirement
      in poorly insulin-treated type 2-diabetic patients; however, these effects are
      mostly limited to three months. With additional glitazone treatment after the
      insulin infusion, the improvement in metabolic control and the reduced insulin
      requirement can be maintained for more than six months.

PMID- 17009068
TI  - The prevalence of venous insufficiency in patients with chronic obstructive
      pulmonary disease evaluated by color duplex ultrasonography.
AB  - OBJECTIVES: We hypothesized that in patients with chronic obstructive pulmonary
      disease (COPD) some extrapulmonary effects such as increase in intra-abdominal
      and intra-thoracic pressures, presence of cor pulmonale and pulmonary artery
      hypertension could cause venous insufficiency (VI) in the lower limbs. Our aim in
      this study was to assess the prevalence of VI in patients with COPD in comparison
      with healthy controls. METHODS: Thirty-nine male patients with COPD and 36
      healthy male controls were evaluated for VI. All the participants were in the
      same age group and their smoking intensities were similar. Patients with COPD
      were classified as having mild, moderate, severe or very severe disease according
      to criteria of the Global Initiative for Chronic Obstructive Lung Disease. All
      the patients and control group were examined for unilateral or bilateral VI of
      the common femoral vein, superficial femoral vein, deep femoral vein and
      popliteal vein using color duplex ultrasonography. RESULTS: The prevalence of VI
      of the lower extremity in patients with COPD (69.2%) was significantly higher
      than in the healthy control group (41.7%). The prevalence increased as the COPD
      severity increased and VI was detected in all the patients with very severe COPD
      [mild COPD, 50.0% (2/4); moderate, 58.8% (10/17); severe, 75.0% (9/12); very
      severe, 100% (6/6)]. CONCLUSION: VI of the lower extremity appears more frequent
      in patients with COPD. We suggest ruling out COPD in patients with otherwise
      unexplained "primary" VI.

PMID- 17009069
TI  - Neurosarcoidosis--a diagnostic pitfall with consequences.
AB  - Neurosarcoidosis is often a diagnostic dilemma, especially in the absence of
      other organ involvement. We report a 64-year-old patient who had suffered from
      paraplegia due to an intramedullar process since 1995. The presumptive diagnosis
      based on computed tomography was spinal cord infarction. Six years later, he
      complained about increasing paresthesia. Magnetic resonance imaging of the spinal
      cord showed nodular meningeal enhancement. Computed tomography of the thorax
      revealed mediastinal and hilar lymphadenopathy. Bronchoscopy under generalized
      anesthesia was performed. The differential cell count in bronchoalveolar lavage
      fluid showed 39% lymphocytes and a CD4(+)/CD8(+) ratio of 17.7. Histological
      examination of biopsy specimens from the hilar lymph nodes revealed non
      necrotizing granulomas with epitheloid cells and Langerhans-type giant cells,
      consistent with the diagnosis of sarcoidosis. As a result of these findings,
      lumbar puncture was undertaken and a raised protein concentration and pleocytosis
      were found in the cerebrospinal fluid. The number of lymphocytes (9,250
      lymphocytes/l) and a CD4(+)/CD8(+) ratio of 10.78 led to the diagnosis of
      neurosarcoidosis. Paralysis might have been prevented if the correct diagnosis of
      neurosarcoidosis had been established earlier in this patient.

PMID- 17009070
TI  - Ventricular tachycardia induced by abuse of ephedrine in a young healthy woman.
AB  - INTRODUCTION: Ephedrine or ephedra herbal products have occasionally been used to
      enhance sports performance and energy or to aid weight loss. The most serious
      side effects are those on cardiovascular function, including acute myocardial
      infarction, severe hypertension, myocarditis and lethal cardiac arrhythmias. CASE
      REPORT: A 19-year-old woman was taking ephedrine to enhance her sports
      performance. After 10 days of this medication she developed hemodynamically
      unstable ventricular tachycardia resistant to cardioversion and amiodarone
      treatment. She converted to sinus rhythm 60 hours later, presumably when the
      plasma ephedrine level had sufficiently decreased. In an electrophysiological
      study the ventricular tachycardia could be induced and successfully ablated.
      There were no recurrences during follow-up of more than a year. The use of
      ephedrine carries a risk of development of life-threatening arrhythmias.
      DISCUSSION: Ephedrine alone cannot be considered as the ultimate cause of
      tachycardia in our patient; however, it is highly probable that ephedrine
      triggered the tachycardic attack. The proarrhythmic effect most likely occurred
      because of underlying idiopathic left ventricular tachycardia. Although the
      patient could have developed her first attack of ventricular tachycardia at any
      time in her life, it is highly improbable that the attack following the ephedrine
      abuse was purely coincidental. CONCLUSION: Our experience with the reported
      patient shows that ephedrine alone, or in combination with substances that
      increase its effects on the cardiovascular system, may also trigger paroxysms of
      non-ischemic ventricular tachycardia. The use of ephedrine carries a risk of
      development of life-threatening arrhythmias and should be discouraged.

PMID- 17009072
TI  - Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai
      patients.
AB  - Mutation and polymorphism data for Hirschsprung disease (HSCR) varies among
      ethnic groups. Single nucleotide polymorphisms (SNP) of RET proto-oncogene (RET)
      were recently shown to be associated with the disease, and with disease severity,
      in different populations. In this study, comprehensive analysis of RET, GDNF,
      EDNRB, ET-3, and SOX-10 genes among sporadic HSCR in Thailand was conducted by
      standard PCR-SSCP, RFLP, and sequencing methods. Of 41 patients, 30 cases had
      rectosigmoid disease (RSD) and 11 cases were assigned to the long-segment disease
      (LSD) group. Four missense mutations of RET, S100M, R231H, T278N, and G533S, were
      identified in three patients. One novel missense mutation, V111Q, was detected in
      EDNRB. For ET-3, two novel missense mutations, D166E and C173R, occurred
      concomitantly in a patient. The incidence of missense mutation was significantly
      higher in our female HSCR patient than in the male counterpart. Statistical
      analysis of the SNPs revealed a significant difference between allele
      distribution of RET L769L in patients in the LSD and RSD groups. The predominant
      genotype construct of RET A45A/L769L in our HSCR was GG/GG, which is obviously
      different from results from all previous studies. The GG/GG genotype construct
      was associated with RSD and with males. The study also detected a variant allele
      of RET S836S which has never been reported in Asian cohorts.

PMID- 17009073
TI  - Phylogenetic, ontogenetic, and pathological aspects of the urine-concentrating
      mechanism.
AB  - The urine-concentrating mechanism is one of the most fundamental functions of
      avian and mammalian kidneys. This particular function of the kidneys developed as
      a system to accumulate NaCl in birds and as a system to accumulate NaCl and urea
      in mammals. Based on phylogenetic evidence, the mammalian urine-concentrating
      mechanism may have evolved as a modification of the renal medulla's NaCl
      accumulating system that is observed in birds. This qualitative conversion of the
      urine-concentrating mechanism in the mammalian inner medulla of the kidneys may
      occur during the neonatal period. Human kidneys have several suboptimal features
      caused by the neonatal conversion of the urine-concentrating mechanism. The urine
      concentrating mechanism is composed of various functional molecules, including
      water channels, solute transporters, and vasopressin receptors. Abnormalities in
      water channels aquaporin (AQP)1 and AQP2, as well as in the vasopressin receptor
      V2R, are known to cause nephrogenic diabetes insipidus. An analysis of the
      pathological mechanism involved in nephrogenic diabetes insipidus suggests that
      molecular chaperones may improve the intracellular trafficking of AQP2 and V2R,
      and, in the near future, such chaperones may become a new clinical tool for
      treating nephrogenic diabetes insipidus.

PMID- 17009074
TI  - Regulation of parathyroid function in chronic kidney disease (CKD).
AB  - In chronic kidney disease (CKD), several abnormalities in bone and mineral
      metabolism develop in the majority of patients. The parathyroid plays a very
      important role in regulating bone and mineral metabolism; thus, control of
      parathyroid function is one of the main targets of the management of CKD-mineral
      and bone disorder (CKD-MBD). In the development of secondary hyperparathyroidism,
      it has recently been suggested that fibroblast growth factor 23 (FGF23) plays a
      crucial role, both as a phosphaturic factor and as a suppressor of active vitamin
      D (1,25D) production in the kidney. FGF23 is originally secreted to prevent
      hyperphosphatemia in CKD, but this occurs at the expense of low 1,25D and
      hyperparathyroidism ("trade-off" hypothesis revisited). Furthermore, recent data
      suggest that FGF23 could be another useful marker for the prognosis of
      hyperparathyroidism, because a high serum level may reflect the cumulative dose
      of vitamin D analogues previously administered. We have also demonstrated that
      severe hyperparathyroidism was associated with the production and secretion of a
      new form of parathyroid hormone (PTH) molecule, which can be detected by third
      generation assays for PTH, but not by the second-generation assays. For the
      regression of already established nodular hyperplasia, the more advanced type of
      parathyroid hyperplasia, it is certainly necessary, in the near future, to
      develop new agents that specifically induce apoptosis in parathyroid cells. Until
      such agents are developed, prevention and early recognition of nodular
      hyperplasia is mandatory for the effective and safe management of
      hyperparathyroidism in CKD.

PMID- 17009075
TI  - Abnormal glycosylation of serum IgG in patients with IgA nephropathy.
AB  - BACKGROUND: We postulated that IgA nephropathy (IgAN) involved alterations of
      serum IgG. The present study was undertaken to elucidate changes in serum IgG
      oligosaccharide structure analysis and to assess the diagnostic usefulness of
      this analysis in IgAN. METHODS: The subjects were 28 children who were
      definitively diagnosed as having IgAN on the basis of renal biopsy and who had
      not received treatment for this disease; 27 healthy children; 15 untreated adults
      definitely diagnosed as having IgAN; 5 patients with other nephropathies; and 61
      healthy adults. Oligosaccharide analyses of IgG were performed by reverse-phase
      high-performance liquid chromatography (HPLC) developed by Takahashi and
      colleagues. RESULTS: In both the children and the adults, the peak area ratio of
      isomers with two different galactosyl-N-acetylglucosamine (Gal-GlcNAc) binding
      sites was significantly lower in the presence of IgAN than in the healthy
      subjects (P<0.05 in children and P<0.001 in adults). The ratio of Gal-free
      oligosaccharides to Gal-positive oligosaccharides did not differ according to the
      presence or absence of IgAN in children or in adults. CONCLUSIONS: The analysis
      of the oligosaccharide structure of serum IgG seems to be useful in diagnosing
      IgAN.

PMID- 17009076
TI  - Correlations of tissue macrophages and cytoskeletal protein expression with renal
      fibrosis in patients with diabetes mellitus.
AB  - BACKGROUND: In clinicopathological studies of cellular remodeling in the
      progression of diabetic nephropathy, it has not been well described whether
      tissue macrophage numbers and the expression of two cytoskeletal proteins--alpha
      smooth muscle actin (alphaSMA) and vimentin--correlate with the disease severity.
      METHODS: Renal biopsy specimens from 23 patients with noninsulin-dependent
      diabetes mellitus (NIDDM) were examined by immunoperoxidase methods for CD68+
      macrophages and alphaSMA and vimentin staining in paraffin-embedded samples.
      alphaSMA staining was evaluated in mesangial and interstitial myofibroblastic
      cells, and vimentin staining was evaluated in podocytes and mesangial and tubular
      cells. RESULTS: Glomerular macrophage numbers were not correlated with any
      clinicopathological scores. However, the interstitial macrophage score was
      significantly correlated with serum creatinine (sCr) and strongly correlated with
      the interstitial fibrosis score. Both alphaSMA and vimentin were detectable in
      the mesangium, without significant correlation with each other. A positive
      correlation was observed between mesangial alphaSMA and urinary (u-) protein
      levels. In contrast, an inverse correlation was observed between levels of
      mesangial vimentin and u-protein. Mesangial alphaSMA, but not vimentin, showed a
      significant correlation with glomerular sclerosis. Podocytic vimentin levels
      tended to decrease in patients with higher sCr levels. The severity of
      interstitial peritubular alphaSMA was correlated strongly with interstitial
      macrophage proliferation and significantly with the interstitial fibrosis score.
      CONCLUSIONS: The expression of mesangial alphaSMA may play a role in the
      progression of glomerular damage, while, on the other hand, newly acquired
      mesangial vimentin seems to be attenuated by heavy proteinuria. In addition, it
      was suggested that peritubular alphaSMA-positive myofibroblastic cells, in
      collaboration with interstitial macrophages, contribute to the progression of
      interstitial fibrosis in diabetic nephropathy.

PMID- 17009077
TI  - Renin angiotensin aldosterone system blockade and renal disease in patients with
      type 2 diabetes: a subanalysis of Japanese patients from the RENAAL study.
AB  - BACKGROUND: The Reduction of Endpoints in NIDDM with the Angiotensin II
      Antagonist Losartan (RENAAL) study has previously shown losartan to confer
      significant benefits to patients with type 2 diabetes and nephropathy. The
      original study of 1513 patients included 96 Japanese patients; the present study
      is a post-hoc analysis of the effects of losartan in this Japanese subpopulation.
      METHODS: This double-blind, randomized study compared losartan (50 to 100 mg once
      daily) with placebo. The study medication was taken in addition to conventional
      antihypertensive treatment, and the mean follow-up period for the Japanese
      patients was 2.8 years. The primary endpoint was the composite of doubling of
      serum creatinine, endstage renal disease, or death. Secondary endpoints included
      changes in proteinuria levels. Safety was also evaluated. RESULTS: The primary
      composite endpoint was reached in fewer Japanese patients receiving losartan than
      placebo (50.0% versus 65.4%, respectively). The treatment effects of losartan
      were more robust when data were corrected for differences in proteinuria at
      baseline--a significant relative risk reduction of 45% with losartan (P=0.0397)
      was apparent. Treatment benefit exceeded that attributable to blood pressure
      changes alone. Levels of proteinuria were reduced with losartan compared with
      placebo, with an overall losartan treatment effect of 37.8% (P<0.001). Overall,
      losartan was similarly well tolerated in both the Japanese patients and the total
      population. CONCLUSIONS: In Japanese patients with type 2 diabetes and
      nephropathy, losartan offers renal protection and is generally well tolerated.

PMID- 17009079
TI  - Performance of polysulfone membrane dialyzers and dialysate flow pattern.
AB  - BACKGROUND: It is important to observe the flow pattern of dialysate when
      evaluating dialyzer function and developing the most appropriate design. We
      investigated dialysate flow through two polysulfone membrane dialyzers (TS-UL
      [Toray Medical] and APS-S [Asahi Medical]) by computed tomography (CT), with
      barium sulfate as the contrast medium. We also performed a clinical comparison of
      these two dialyzers. METHODS: For the in vitro experiment, after confirming the
      steady-state flow of mock blood (xanthan gum solution; 200 ml/min) and dialysate
      (500 ml/min), fresh dialysate, containing 5% (w/v) barium sulfate was perfused,
      and longitudinal CT scans of the dialyzer were obtained. Then the concentration
      of barium sulfate was measured (in Hounsfield units) in three fixed regions of
      interest. For the in vivo experiment, 12 patients on stable hemodialysis who had
      been using the APS-S for more than 1 month were switched to the TS-UL for 1 month
      and changes in various parameters were assessed. RESULTS: The distribution of
      dialysate was homogeneous on CT scans of the TS-UL, but not on scans of the APS
      S. The dialysate concentration curves for the three regions of interest were
      similar with the TS-UL, but not with the APS-S. Clearance of urea nitrogen and
      albumin loss were both significantly higher with the TS-UL than with the APS-S.
      The decrease in alpha 1-microglobulin was larger with the TS-UL than with the APS
      S, but not significantly. CONCLUSIONS: Clearance of substances over a wide range
      of molecular weights was higher with the TS-UL than with the APS-S, and
      differences in the design of the dialysate compartment may have been involved in
      this feature.

PMID- 17009078
TI  - Efficacy, safety and tolerability of atorvastatin in dyslipidemic subjects with
      advanced (non-nephrotic) and endstage chronic renal failure.
AB  - BACKGROUND: Patients with dyslipidemia and advanced renal failure are at markedly
      increased risk of cardiovascular morbidity and mortality. We evaluated the
      efficacy, safety, and tolerability of atorvastatin in non-nephrotic, dyslipidemic
      patients with chronic renal failure (CRF) or endstage renal failure (ESRF)
      receiving dialysis. METHODS: Following a 6-week baseline period, adult patients
      meeting Australian Heart Foundation treatment guidelines received atorvastatin
      for 16 weeks: 19 with CRF (predialysis), 17 on hemodialysis (HD), and 13 on
      continuous ambulatory peritoneal dialysis (CAPD). Dose (10-40 mg daily) was
      titrated to achieve lipid-lowering targets. Efficacy was determined by monitoring
      lipids (principally triglycerides and low-density lipoprotein [LDL] cholesterol);
      safety and tolerance by monitoring clinical and laboratory parameters. RESULTS:
      Atorvastatin was effective in reducing LDL cholesterol from baseline at each of
      weeks 4, 8, 12, and 16 in all study groups, with reductions of more than 40% at
      week 16. Sixty-two percent of PD, 73% of HD, and 100% of CRF patients were at or
      below target (<2.6 mmol/l) for LDL cholesterol at week 16. Significant reductions
      in triglycerides (approximately 27%) were seen in the CRF and combined HD/CAPD
      groups at all time points. Depending on the group, 65%-83% of patients were at or
      below target (<2.0 mmol/l) for triglycerides at week 16. The majority of patients
      received the 10-mg dose. Atorvastatin also reduced total cholesterol and
      apolipoprotein B levels in all groups and very-low-density lipoprotein (VLDL)
      cholesterol in the CRF group. Significant increases in LDL particle size were
      found in the HD and combined HD/CAPD groups. Minor, particularly
      gastrointestinal, symptoms were common. Three patients reported musculoskeletal
      symptoms, but creatine kinase was raised in only one. CONCLUSION: Atorvastatin is
      an effective lipid-lowering agent for dyslipidemic subjects with advanced and
      endstage renal failure, and was reasonably well tolerated.

PMID- 17009080
TI  - Tubulointerstitial nephritis and uveitis syndrome associated with
      hyperthyroidism.
AB  - We report a 17-year-old male patient with tubulointerstitial nephritis and
      uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month
      history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss
      when he was admitted to our hospital. He had iritis, which was complicated by
      fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory
      examinations, deteriorated renal function (blood urea nitrogen level was 25.9
      mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N
      acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600
      microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was
      undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free
      thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The
      titers of antithyroglobulin and antithyroid microsomal and TSH-receptor
      antibodies were not elevated. Abdominal and thyroidal ultrasonography showed
      evident bilateral enlargement of the kidneys and diffuse enlargement of the
      thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland.
      The biopsied renal specimen showed mild edema and severe diffuse infiltration of
      mononuclear cells and few eosinophils in the interstitium, without any glomerular
      or vascular abnormalities. Based on the clinical features and pathological
      findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made.
      Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and
      the patient's clinical status improved remarkably. This case suggests the
      possibility of thyroid dysfunction in some patients with TINU syndrome, and we
      believe thyroid function should be measured in all TINU patients. Moreover,
      histopathological diagnosis of the thyroid glands before treatment is necessary
      for TINU patients with thyroid dysfunction.

PMID- 17009081
TI  - Nephrotic syndrome associated with interferon-beta-1b therapy for multiple
      sclerosis.
AB  - A 43-year-old woman with multiple sclerosis (MS) had nephrotic syndrome 21 months
      after starting treatment with interferon (IFN)-beta-1b (subcutaneous
      administration). She had taken no drug except for the IFN-beta-1b. Because
      nephrotic syndrome may be induced by IFN therapy, the IFN was stopped.
      Percutaneous renal biopsy revealed that she had minimal change nephrotic
      syndrome. As nephrotic-range proteinuria, hypoalbuminemia, and general edema were
      worsening even 2 weeks after cessation of the drug, oral corticosteroid therapy
      (prednisolone 40 mg/day) was started. The nephrotic syndrome was treated
      successfully with prednisolone. The dosage of prednisolone was tapered, without a
      relapse, and then the corticosteroid therapy was stopped. IFN-beta-1b therapy was
      then resumed, and the patient is in remission for both nephrotic syndrome and MS.
      Though proteinuria and nephrotic syndrome is a rare adverse effect of IFN-beta-1b
      therapy, physicians treating MS patients with this agent should pay careful
      attention to new clinical symptoms and laboratory findings.

PMID- 17009082
TI  - Japanese subpopulation analysis of the RENAAL, the landmark trial, is welcomed by
      our society.

PMID- 17009083
TI  - An economic evaluation of strontium ranelate in the treatment of osteoporosis in
      a Swedish setting: based on the results of the SOTI and TROPOS trials.
AB  - INTRODUCTION: Strontium ranelate is a new therapy for the treatment and
      prevention of osteoporosis that has been shown in two phase III clinical trials
      (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and the Treatment Of
      Peripheral OSteoporosis Study [TROPOS] trials) to reduce the risk of osteoporotic
      fractures at the vertebral, non-vertebral and hip level in postmenopausal women.
      The aim of this study was to estimate the potential cost-effectiveness of
      strontium ranelate in the treatment of osteoporosis in postmenopausal Swedish
      patients. METHODS: A Markov cohort model was adapted to fit patients
      corresponding to the patients in the SOTI and TROPOS clinical trials. The model
      was populated with Swedish cost and epidemiological data. In the base case, the
      cost-effectiveness was estimated for 69-year old women with low bone mineral
      density (BMD) and prevalent vertebral fractures (SOTI) and for 77-year old women
      with low BMD (TROPOS). The cost-effectiveness analysis had a societal
      perspective. RESULTS: In the base case analysis, the cost per quality-adjusted
      life years (QALY) gained of strontium ranelate patients compared to no treatment
      patients was estimated at SEK 472,586 and SEK 259,643, including costs in added
      life years, based on the SOTI and the TROPOS trials, respectively. Excluding cost
      in added life years, the cost per QALY gained was estimated at SEK 336,420 (SOTI)
      and SEK 165,680 (TROPOS). In subgroup analyses, in patients 74 years and older
      with a T-score lower than -2.4 and patients older than 80 years of age, strontium
      ranelate was found to be cost saving compared to no treatment. CONCLUSIONS: The
      results in the base case analyses and the sensitivity analyses of this study
      indicate that, compared to no treatment, strontium ranelate is cost-effective in
      the treatment of postmenopausal women with low BMD.

PMID- 17009084
TI  - An Arabidopsis thaliana virescent mutant reveals a role for ClpR1 in plastid
      development.
AB  - The ATP-dependent Clp protease has been well-characterized in Escherichia coli,
      but knowledge of its function in higher plants is limited. In bacteria, this two
      component protease consists of a Ser-type endopeptidase ClpP, which relies on the
      ATP-dependent unfolding activity from an Hsp100 molecular chaperone to initiate
      protein degradation. In the chloroplasts of higher plants, multiple isoforms of
      the proteolytic subunit exist, with Arabidopsis having five ClpPs and four ClpP
      like proteins termed ClpR predicted in its genome. In this work we characterized
      an Arabidopsis mutant impaired in one subunit of the chloroplast-localized Clp
      protease core, ClpR1. clpR1-1, a virescent mutant, carries a pre-mature stop
      codon in the clpR1 gene, resulting in no detectable ClpR1 protein. The
      accumulation of several chloroplast proteins, as well as most of the chloroplast
      localized Clp protease subunits, is inhibited in clpR1-1. Unexpectedly, some
      plastid-encoded proteins do not accumulate, although their transcripts accumulate
      to wild-type levels. Maturation of 23S and 4.5S chloroplast ribosomal RNA (cp
      rRNA) is delayed in clpR1-1, and both RNAs accumulate as higher molecular weight
      precursors. Also, chloroplasts in clpR1-1 are smaller than in wild type and have
      fewer thylakoid membranes with smaller grana stacks. We propose that a ClpR1
      containing activity is required for chloroplast development and differentiation
      and in its absence both are delayed.

PMID- 17009085
TI  - MDCT and virtual angioscopy in spontaneous aortocaval fistula.
AB  - Aortocaval fistula is a rare, less than 1%, but life threatening complication, of
      abdominal aortic aneurysm. Mortality is high but prompt recognition of the
      fistula can reduce mortality rate. The multidetector row CT (MDCT) findings in a
      69-year-old patient with a complex medical history characterized by previous
      episodes of myocardial ischemia, is reported. MDCT shows an early homogeneous
      enhancement of the inferior vena cava, slightly dilated at the liver level and
      markedly narrowed above the renal vein due to aneurysm compression. The patient
      underwent to emergency laparotomy but died during surgery for cardiac arrest.
      MDCT allows a prompt recognition of the fistula and different computerized
      reconstruction techniques as maximum intensity projection (MIP), multiplanar
      reformatting (MPR) and virtual angioscopy (VA) added imaging information for
      surgery.

PMID- 17009086
TI  - The prevalence of person-perceived participation restriction in community
      dwelling older adults.
AB  - OBJECTIVE: To estimate the prevalence, nature and distribution of person
      perceived participation restriction, in community-dwelling older adults. METHOD:
      Population based cross-sectional postal survey of 11,055 adults aged 50 years and
      over in North Staffordshire, United Kingdom. Person-perceived participation
      restriction was measured using the Keele Assessment of Participation which covers
      11 different aspects of life mapped to the World Health Organization's
      International Classification of Functioning. Four-week period prevalence was
      calculated for restriction in any, multiple and for each aspect separately.
      Prevalence estimates were calculated for the total sample, and for each age and
      gender stratum. RESULTS: A total of 7,878 subjects responded (adjusted response-
      71.3%). The 4-week period prevalence of any participation restriction was 51.8%;
      3.3% had substantial restriction. Participation restriction increased with age
      (p<0.001) and, for moderate and substantial restriction, was more frequent in
      women. The prevalence of restricted participation in individual aspects of life
      ranged from 3.8% (work) to 25.9% (mobility outside the home). CONCLUSION: Some
      restriction of participation 'as and when we want it' is common in the general
      population and increases with age, although severe restriction only affects a
      minority. The distribution of person-perceived participation restriction is
      similar to that of impairments and activity limitation in community-dwelling
      older adults.

PMID- 17009088
TI  - Catabolic pathways and biotechnological applications of microbial caffeine
      degradation.
AB  - Catabolism of caffeine (1,3,7-trimethylxanthine) in microorganisms commences via
      two possible mechanisms: demethylation and oxidation. Through the demethylation
      route, the major metabolite formed in fungi is theophylline (1,3
      dimethylxanthine), whereas theobromine (3,7-dimethylxanthine) is the major
      metabolite in bacteria. In certain bacterial species, caffeine has also been
      oxidized directly to trimethyl uric acid in a single step. The conversion of
      caffeine to its metabolites is primarily brought about by N-demethylases (such as
      caffeine demethylase, theobromine demethylase and heteroxanthinedemethylase),
      caffeine oxidase and xanthine oxidase that are produced by several caffeine
      degrading bacterial species such as Pseudomonas putida and species within the
      genera Alcaligenes, Rhodococcus and Klebsiella. Development of biodecaffeination
      techniques using these enzymes or using whole cells offers an attractive
      alternative to the present existing chemical and physical methods removal of
      caffeine, which are costly, toxic and non-specific to caffeine. This review
      mainly focuses on the biochemistry of microbial caffeine degradation, presenting
      recent advances and the potential biotechnological application of caffeine
      degrading enzymes.

PMID- 17009087
TI  - Hepatitis C infection in dialysis patients: a link to poor clinical outcome?
AB  - Among the 350,000 maintenance dialysis patients in the USA, the mortality rate is
      high (20-23% per year) as is the prevalence of hepatitis C virus (HCV) infection
      (5-15%). An additional same number of dialysis patients in the USA may be
      infected with HCV but have undetectable HCV antibodies. Almost half of all deaths
      in dialysis patients, including HCV-infected patients, are due to cardiovascular
      disease. Since over two-thirds of dialysis patients die within 5 years of
      initiating dialysis and because markers of malnutrition-inflammation complex
      syndrome (MICS), rather than traditional cardiovascular risk factors, are among
      the strongest predictors of early death in these patients, the impact of HCV
      infection on nutritional status and inflammation may be a main cause of poor
      survival in this population. Based on data from our cross-sectional and limited
      longitudinal studies, we hypothesize that HCV infection confounds the association
      between MICS and clinical outcomes in dialysis patients and, by doing so, leads
      to higher short-term cardiovascular events and death. Understanding the natural
      history of HCV and its association with inflammation, nutrition and outcomes in
      dialysis patients may lead to testing more effective anti-HCV management
      strategies in this and other similar patient populations, providing benefits not
      only for HCV infection but the detrimental consequences associated with this
      infection. In this article, we review the link between the HCV infection and
      mortality in dialysis patients and compare HCV antibody to molecular methods to
      detect HCV infection in these individuals.

PMID- 17009089
TI  - Ex situ bioremediation of phenol contaminated soil using polymer beads.
AB  - Polymer beads have been used to absorb high concentrations of phenol from soil
      decreasing the initial concentration of 2.3 g kg(-1) soil to 100 mg kg(-1) soil
      and achieving a phenol loading within the polymer beads of 27.5 mg phenol g(-1)
      beads. The phenol-loaded polymer beads were removed from the soil and placed in a
      bioreactor, which was then inoculated with a phenol-degrading microbial
      consortium. All of the phenol contained within the polymer beads was shown to
      desorb from the polymer matrix and was degraded by the microbial consortium. The
      beads were used again (twice) in a similar manner with no loss in performance.

PMID- 17009090
TI  - Multiple glycerol shocks increase the calcium phosphate transfection of non
      synchronized CHO cells.
AB  - The exposure of CHO DG44 cells to an osmotic shock, after DNA uptake, results in
      a cellular volume decrease of approx. 55%. Repetitive osmotic shocks targeted
      different sub-populations of cells as was demonstrated using two different
      fluorescent reporter genes. Also the exposure of a calcium phosphate-DNA
      coprecipitate to high osmolarity in vitro caused the release of the DNA from the
      precipitate. The results demonstrate the importance of the osmotic shock on the
      efficient delivery of plasmid DNA to the nucleus of CHO cells following calcium
      phosphate-mediated transfection.

PMID- 17009092
TI  - High-throughput structure-based pharmacophore modelling as a basis for successful
      parallel virtual screening.
AB  - In order to assess bioactivity profiles for small organic molecules we propose to
      use parallel pharmacophore-based virtual screening. Our aim is to provide a fast,
      reliable and scalable system that allows for rapid in silico activity profile
      prediction of virtual molecules. In this proof of principle study, carried out
      with the new structure-based pharmacophore modelling tool LigandScout and the
      high-performance database mining platform Catalyst, we present a model work for
      the application of parallel pharmacophore-based virtual screening on a set of 50
      structure-based pharmacophore models built for various viral targets and 100
      antiviral compounds. The latter were screened against all pharmacophore models in
      order to determine if their known biological targets could be correctly predicted
      via an enrichment of corresponding pharmaco-phores matching these ligands. The
      results demonstrate that the desired enrichment, i.e. a successful activity
      profiling, was achieved for approximately 90% of all input molecules.
      Additionally, we discuss descriptors for output validation, as well as various
      aspects influencing the analysis of the obtained activity profiles, and the
      effect of the searching mode utilized for screening. The results of the study
      presented here clearly indicate that pharmacophore-based parallel screening
      comprises a reliable in silico method to predict the potential biological
      activities of a compound or a compound library by screening it against a series
      of pharmacophore queries.

PMID- 17009091
TI  - A combined ligand-based and target-based drug design approach for G-protein
      coupled receptors: application to salvinorin A, a selective kappa opioid receptor
      agonist.
AB  - Combined ligand-based and target-based drug design approaches provide a
      synergistic advantage over either method individually. Therefore, we set out to
      develop a powerful virtual screening model to identify novel molecular scaffolds
      as potential leads for the human KOP (hKOP) receptor employing a combined
      approach. Utilizing a set of recently reported derivatives of salvinorin A, a
      structurally unique KOP receptor agonist, a pharmacophore model was developed
      that consisted of two hydrogen bond acceptor and three hydrophobic features. The
      model was cross-validated by randomizing the data using the CatScramble
      technique. Further validation was carried out using a test set that performed
      well in classifying active and inactive molecules correctly. Simultaneously, a
      bovine rhodopsin based "agonist-bound" hKOP receptor model was also generated.
      The model provided more accurate information about the putative binding site of
      salvinorin A based ligands. Several protein structure-checking programs were used
      to validate the model. In addition, this model was in agreement with the mutation
      experiments carried out on KOP receptor. The predictive ability of the model was
      evaluated by docking a set of known KOP receptor agonists into the active site of
      this model. The docked scores correlated reasonably well with experimental pK (i)
      values. It is hypothesized that the integration of these two independently
      generated models would enable a swift and reliable identification of new lead
      compounds that could reduce time and cost of hit finding within the drug
      discovery and development process, particularly in the case of GPCRs.

PMID- 17009093
TI  - Inactive and active states and supramolecular organization of GPCRs: insights
      from computational modeling.
AB  - Herein we make an overview of the results of our computational experiments aimed
      at gaining insight into the molecular mechanisms of GPCR functioning either in
      their normal conditions or when hit by gain-of-function or loss-of-function
      mutations. Molecular simulations of a number of GPCRs in their wild type and
      mutated as well as free and ligand-bound forms were instrumental in inferring the
      structural features, which differentiate the mutation- and ligand-induced active
      from the inactive states. These features essentially reside in the interaction
      pattern of the E/DRY arginine and in the degree of solvent exposure of selected
      cytosolic domains. Indeed, the active states differ from the inactive ones in the
      weakening of the interactions made by the highly conserved arginine and in the
      increase in solvent accessibility of the cytosolic interface between helices 3
      and 6. Where possible, the structural hallmarks of the active and inactive
      receptor states are translated into molecular descriptors useful for in silico
      functional screening of novel receptor mutants or ligands. Computational modeling
      of the supramolecular organization of GPCRs and their intracellular partners is
      the current challenge toward a deep understanding of their functioning
      mechanisms.

PMID- 17009095
TI  - A cost efficiency comparison between the multiple mini-interview and traditional
      admissions interviews.
AB  - A major expense for most professional training programs, both financially and in
      terms of human resources, is the interview process used to make admissions
      decisions. Still, most programs view this as a necessary cost given that the
      personal interview provides an opportunity to recruit potential candidates,
      showing them what the program has to offer, and to try and gather more
      information about the candidates to ensure that those selected live up to the
      espoused values of the institution. We now have five years worth of experience
      with a Multiple Mini-Interview (MMI) process that, unlike traditional panel
      interviews, uses the OSCE model to have candidates interact with a larger number
      of interviewers. We have found that the MMI is more reliable and has better
      predictive power than our traditional panel interviews. Still, the extent to
      which any measurement is valuable depends also on the feasibility of use. In this
      paper we report on an exploration of the cost effectiveness of the MMI as
      compared to standard panel-based interviews by considering the generation of
      interview material, human resource (i.e., interviewer and support staff) use,
      infrastructure requirements, and other miscellaneous expenses. Our conclusion is
      that the MMI requires greater preparatory efforts and a larger number of rooms to
      carry out the interviews relative to panel-based interviews, but that these cost
      disadvantages are offset by the MMI requiring fewer person-hours of effort. The
      absolute costs will vary dependent on institution, but the framework presented in
      this paper will hopefully provide greater guidance regarding logistical
      requirements and anticipated budget.

PMID- 17009094
TI  - Comparative residue interaction analysis (CoRIA): a 3D-QSAR approach to explore
      the binding contributions of active site residues with ligands.
AB  - A novel approach termed comparative residue-interaction analysis (CoRIA),
      emphasizing the trends and principles of QSAR in a ligand-receptor environment
      has been developed to analyze and predict the binding affinity of enzyme
      inhibitors. To test this new approach, a training set of 36 COX-2 inhibitors
      belonging to nine families was selected. The putative binding (bioactive)
      conformations of inhibitors in the COX-2 active site were searched using the
      program DOCK. The docked configurations were further refined by a combination of
      Monte Carlo and simulated annealing methods with the Affinity program. The non
      bonded interaction energies of the inhibitors with the individual amino acid
      residues in the active site were then computed. These interaction energies, plus
      specific terms describing the thermodynamics of ligand-enzyme binding, were
      correlated to the biological activity with G/PLS. The various QSAR models
      obtained were validated internally by cross validation and boot strapping, and
      externally using a test set of 13 molecules. The QSAR models developed on the
      CoRIA formalism were robust with good r (2), q (2) and r (pred) (2) values. The
      major highlights of the method are: adaptation of the QSAR formalism in a
      receptor setting to answer both the type (qualitative) and the extent
      (quantitative) of ligand-receptor binding, and use of descriptors that account
      for the complete thermodynamics of the ligand-receptor binding. The CoRIA
      approach can be used to identify crucial interactions of inhibitors with the
      enzyme at the residue level, which can be gainfully exploited in optimizing the
      inhibitory activity of ligands. Furthermore, it can be used with advantage to
      guide point mutation studies. As regards the COX-2 dataset, the CoRIA approach
      shows that improving Coulombic interaction with Pro528 and reducing van der Waals
      interaction with Tyr385 will improve the binding affinity of inhibitors.

PMID- 17009096
TI  - Advances in transgenic rat production.
AB  - Predictable and reproducible production of transgenic rats from a standardized
      input of egg donors and egg recipients is essential for routine rat model
      production. In the course of establishing a transgenic rat service, transgenic
      founders were produced from three transgenes in outbred Sprague-Dawley (SD) rats
      and four transgenes in inbred Fischer 344 (F344) rats. Key parameters that affect
      transgenesis efficiency were assessed, including superovulation treatments,
      methods to prepare pseudopregnant recipients, and microinjection technique. Five
      superovulation regimens were compared and treatment with 20 IU PMSG and 30 IU HCG
      was selected for routine use. Four methods to prepare pseudopregnant egg
      recipients were compared and estrus synchronization with LHRHa and mating to
      vasectomized males was selected as most effective. More than 80% of eggs survived
      microinjection when modified pronuclear microinjection needles and DNA buffers
      were used. The efficiencies of transgenic production in rats and C57BL/6J (B6J)
      mice were compared to provide a context for assessing the difficulty of
      transgenic rat production. Compared to B6J mice, SD rat transgenesis required
      fewer egg donors per founder, fewer pseudopregnant egg recipients per founder,
      and produced more founders per eggs microinjected. Similar numbers of injection
      days were required to produce founders. These results suggest that SD rat
      transgenesis can be more efficient than B6J mouse transgenesis with the
      appropriate technical refinements. Advances in transgenic rat production have the
      potential to increase access to rat models.

PMID- 17009097
TI  - Adriamycin-induced oxidative mitochondrial cardiotoxicity.
AB  - The anticancer agent Adriamycin (ADR) has long been recognized to induce a dose
      limiting cardiotoxicity. Numerous studies have attempted to characterize and
      elucidate the mechanism(s) behind its cardiotoxic effect. Despite a wealth of
      data covering a wide-range of effects mediated by the drug, the definitive
      mechanism remains a matter of debate. However, there is consensus that this
      toxicity is related to the induction of reactive oxygen species (ROS). Induction
      of ROS in the heart by ADR occurs via redox cycling of the drug at complex I of
      the electron transport chain. Many studies support the theory that mitochondria
      are a primary target of ADR-induced oxidative stress, both acutely and long-term.
      This review focuses on the effects of ADR redox cycling on the mitochondrion,
      which support the hypothesis that these organelles are indeed a major factor in
      ADR cardiotoxicity. This review has been constructed with particular emphasis on
      studies utilizing cardiac models with clinically relevant doses or concentrations
      of ADR in the hope of advancing our understanding of the mechanisms of ADR
      toxicity. This compilation of current data may reveal valuable insights for the
      development of therapeutic strategies better tailored to minimizing the dose
      limiting effect of ADR.

PMID- 17009098
TI  - The effects of dexfenfluramine administration on brain serotonin immunoreactivity
      and lipid peroxidation in mice.
AB  - Obesity continues to be an increasing health problem in worldwide and antiobesity
      drugs have commonly been used by obese patients. During the use of anorectic
      drugs, the antioxidant defense may be affected, especially by reactive oxygen
      species. It was decided to investigate the effects of dexfenfluramine on body
      weight, daily food intake, brain thiobarbituric acid-reactive substances (TBARS),
      glutathione (GSH) and nitric oxide (NO) levels, and 5-HT immunoreactivity. Mice
      were divided into two groups each containing 8 Swiss Albino adult (6 months)
      mice. Group 1, untreated, was used as a control; group 2 was treated with
      dexfenfluramine 0.4 mg/kg per day intraperitoneally for 7 days. Brain TBARS and
      GSH levels were assayed spectrophotometrically. The stable end-products of NO,
      nitrite and nitrate, were analyzed spectrophotometrically. Brain tissue 5-HT
      immunoreactivity was observed using an immunohistochemical method. There were
      significant decreases in body weight in the dexfenfluramine group (p < 0.05).
      Although brain GSH and NO(x) levels decreased significantly, brain TBARS levels
      increased in the dexfenfluramine group (p < 0.05). Brain 5-HT immunoreactivity
      also increased in the dexfenfluramine-treated group compared to control. In
      conclusion, our findings show that dexfenfluramine is effective in achieving
      weight loss and also increases lipid peroxidation in mouse brain.

PMID- 17009099
TI  - The participation of brain NO synthase in blood pressure control of adult
      spontaneously hypertensive rats.
AB  - Increased blood pressure (BP) in genetic hypertension is usually caused by high
      activity of sympathetic nervous system (SNS) which is enhanced by central
      angiotensin II but lowered by central nitric oxide (NO). We have therefore
      evaluated NO synthase (NOS) activity as well as neuronal NOS (nNOS), inducible
      NOS (iNOS) and endothelial NOS (eNOS) protein expression in brainstem and
      midbrain of adult spontaneously hypertensive rats (SHR) characterized by enhanced
      sympathetic vasoconstriction. We also studied possible participation of brain NO
      in antihypertensive effects of chronic captopril treatment of adult SHR. NOS
      activity was increased in midbrain of SHR compared to Wistar-Kyoto (WKY) rats.
      This could be ascribed to enhanced iNOS expression, whereas nNOS expression was
      unchanged and eNOS expression was reduced in this brain region. In contrast, no
      significant changes of NOS activity were found in brainstem of SHR in which nNOS
      and iNOS expression was unchanged, but eNOS expression was increased. Chronic
      captopril administration lowered BP of adult SHR mainly by attenuation of
      sympathetic tone, whereas the reduction of angiotensin II-dependent
      vasoconstriction and the decrease of residual BP (amelioration of structural
      remodeling of resistance vessels) were less important. This treatment did not
      affect significantly either NOS activity or expression of any NOS isoform in the
      two brain regions. Our data do not support the hypothesis that altered brain NO
      formation contributes to sympathetic hyperactivity and high BP of adult SHR with
      established hypertension.

PMID- 17009100
TI  - Lupeol and its ester inhibit alteration of myocardial permeability in
      cyclophosphamide administered rats.
AB  - Cyclophosphamide (CP), an alkylating agent widely used in cancer chemotherapy
      causes cardiac membrane damage. Lupeol, a pentacyclic triterpene, isolated from
      Crataeva nurvala stem bark and its ester, lupeol linoleate possess a wide range
      of medicinal properties. The effect of lupeol and its ester was evaluated in CP
      induced alterations in cardiac electrolytes in rats. Male albino rats of Wistar
      strain were categorized into 6 groups. Group I served as control. Rats in groups
      II, V and VI were injected intraperitoneally with a single dose of CP (200 mg/kg
      body weight) dissolved in saline. CP treated groups V and VI received lupeol and
      lupeol linoleate (50 mg/kg body weight) respectively, dissolved in olive oil for
      10 days by oral gavage. At the end of the experimental period, urinary risk
      factors, activities of ATPases and electrolytes were measured using standard
      procedures. CP administered rats showed a significant decrease (P < 0.001) in the
      activities of ATPases. It was associated with significant alterations (P < 0.001)
      of electrolytes both in serum and cardiac tissue. The levels of urea, uric acid
      and creatinine were also significantly (P < 0.001) altered in the serum and
      urine. Lupeol and its ester showed reversal of the above alterations induced by
      CP. These findings demonstrate that the supplementation with lupeol and its ester
      could preserve membrane permeability, highlighting their protective effect
      against CP induced cardiotoxicity.

PMID- 17009101
TI  - PKPD model of interleukin-21 effects on thermoregulation in monkeys--application
      and evaluation of stochastic differential equations.
AB  - PURPOSE: To describe the pharmacodynamic effects of recombinant human interleukin
      21 (IL-21) on core body temperature in cynomolgus monkeys using basic mechanisms
      of heat regulation. A major effort was devoted to compare the use of ordinary
      differential equations (ODEs) with stochastic differential equations (SDEs) in
      pharmacokinetic pharmacodynamic (PKPD) modelling. METHODS: A temperature model
      was formulated including circadian rhythm, metabolism, heat loss, and a
      thermoregulatory set-point. This model was formulated as a mixed-effects model
      based on SDEs using NONMEM. RESULTS: The effects of IL-21 were on the set-point
      and the circadian rhythm of metabolism. The model was able to describe a complex
      set of IL-21 induced phenomena, including 1) disappearance of the circadian
      rhythm, 2) no effect after first dose, and 3) high variability after second dose.
      SDEs provided a more realistic description with improved simulation properties,
      and further changed the model into one that could not be falsified by the
      autocorrelation function. CONCLUSIONS: The IL-21 induced effects on
      thermoregulation in cynomolgus monkeys are explained by a biologically plausible
      model. The quality of the model was improved by the use of SDEs.

PMID- 17009102
TI  - A charge pair interaction between Arg282 in transmembrane segment 7 and Asp341 in
      transmembrane segment 8 of hPepT1.
AB  - PURPOSE: To determine whether R282 in transmembrane segment 7 (TMS7) of hPepT1
      forms a salt bridge with D341 in TMS8. METHODS: Mutated hPepT1 transporters
      containing point mutations at R282 and/or D341 were transiently transfected into
      HEK293 cells. Their steady state expression and functional activity were measured
      using immunoprecipitation and 3H-gly-sar uptake, respectively. Gly-sar uptake by
      cysteine mutants (R282C and D341C) was also measured in the presence and absence
      of cysteine-modifying MTS reagents. RESULTS: The reverse-charge mutants R282D
      hPepT1 and D341R-hPepT1 showed significantly reduced gly-sar uptake, but the
      double mutant (R282D/D341R-hPepT1) has functionality comparable to that of wild
      type hPepT1. Gly-sar uptake by R282C-hPepT1 is reduced, but pre-incubation with 1
      mM MTSET, a positively charged cysteine-modifying reagent, restored function to
      wild-type levels. Similarly, pre-incubation of D341C-hPepT1 with 10 mM MTSES, a
      negatively charged cysteine-modifying reagent, increased gly-sar uptake compared
      to unmodified D341C-hPepT1. In contrast, MTSET modification of D341C-hPepT1
      (giving a positive charge at position 341) resulted in significant reduction in
      gly-sar uptake, compared to D341C-hPepT1. CONCLUSION: Our results are consistent
      with a salt bridge between R282 and D341 in hPepT1, and we use these and other
      data to propose a role for the R282-D341 charge pair in the hPepT1 translocation
      mechanism.

PMID- 17009103
TI  - 4-Hydroxyacetophenone-induced choleresis in rats is mediated by the Mrp2
      dependent biliary secretion of its glucuronide conjugate.
AB  - PURPOSE: The present study examined the underlying mechanism by which 4
      hydroxyacetophenone (4-HA), a bioactive compound found in several medicinal
      herbs, exerts its potent stimulatory effects on hepatic bile secretion. METHODS:
      Bile flow, and biliary excretion of 4-HA, its metabolites, and inorganic
      electrolytes was examined in both normal Wistar rats and in TR(-) Wistar rats
      that have a congenital defect in the multidrug resistance-associated protein-2,
      Mrp2/Abcc2. The effects of 4-HA were also examined in animals treated with
      buthionine sulfoximine to decrease hepatic glutathione (GSH) levels. RESULTS: In
      normal rats, 4-HA dramatically increased bile flow rate, whereas it failed to
      exert a choleretic effect in TR(-) rats. This choleresis was not explained by
      increased biliary output of Na(+), K(+), Cl(-) or HCO(3) (-), or by increased
      biliary GSH excretion. Depletion of hepatic GSH with buthionine sulfoximine had
      no effect on the 4-HA-induced choleresis. HPLC analysis revealed that a single
      major compound was present in bile, namely.4-hydroxyacetophenone-4-O-beta
      glucuronide, and that the parent compound was not detected in bile. Biliary
      excretion of the glucuronide was directly correlated with the increases in bile
      flow. In contrast to normal rats, this 4-HA metabolite was not present in bile of
      TR(-) rats. CONCLUSIONS: These results demonstrate that the major biliary
      metabolite of 4-HA in rats is the 4-O-beta-glucuronide, a compound that is
      secreted into bile at high concentrations, and may thus account in large part for
      the choleretic effects of 4-HA. Transport of this metabolite across the
      canalicular membrane into bile requires expression of the Mrp2 transport protein.

PMID- 17009104
TI  - Phylogenetic relationships among indigenous sheep populations in East Asia based
      on five informative blood protein and nonprotein polymorphisms.
AB  - The phylogenetic relationships among 23 local sheep breeds and varieties in East
      Asia were determined based on allele frequency data for five informative and
      polymorphic blood protein and nonprotein loci (transferrin, arylesterase,
      hemoglobin-beta, X-protein, and potassium transport) using electrophoresis and
      ion-densitometric techniques. Comparatively striking differences in the frequency
      distributions, especially of hemoglobin-beta and X-protein alleles, were seen
      between the northern population of the Khalkhas, Bhyanglung, Baruwal, Jakar,
      Sakten, and five Chinese breeds and the southern population of the Bengal, Kagi,
      Lampuchhre, Myanmar, and Sipsu breeds. Clustering analyses using UPGMA and NJ
      methods and principal component analysis, using the data of all populations and
      loci tested, clearly demonstrated the difference. The two population groups are
      divided by the boundary of the Himalayas, and each diverged into three subgroups:
      Mongolian, Tibetan, and Himalayan groups in the north and Indian groups I, II,
      and III in the south. It was noted that the genetic differentiation of
      populations was more distinct in the northern group. These findings strongly
      suggest the existence of at least two large and phylogenetically different gene
      pools of sheep in East Asia.

PMID- 17009105
TI  - Estrogen receptor-beta regulates psoriasin (S100A7) in human breast cancer.
AB  - We have previously observed a paradoxical relationship of the psoriasin/S100A7
      gene with estrogen response in-vitro in ERalpha positive cells but its
      association with ERalpha negative status in-vivo raising the possibility that
      S100A7 might be regulated by ERbeta in breast cancer. Using doxycycline-inducible
      ERbeta and ERalpha expressing MCF-7 cells the hypothesis that psoriasin/S100A7 is
      ERbeta regulated was investigated To explore the relationship between
      psoriasin/S100A7 and ERbeta expression in-vivo, we also assessed a cohort of 233
      ERalpha negative breast tumors using tissue microarrays and immunohistochemistry.
      Psoriasin/S100A7 was increased by 17beta-estradiol (E2) following ERbeta
      induction, in several clones of ERbeta over-expressing but not in the original
      MCF-7 cells, nor clones over-expressing ERalpha. The effect of E2 on
      psoriasin/S100A7 was inhibited by 4-hydroxytamoxifen and ICI 182780 but not with
      a selective ERalpha antagonist. An ERbeta selective-agonist but not an ERalpha
      selective-agonist, induced psoriasin/S100A7. This induction still occurred after
      stable down-regulation of ERalpha using siRNA in ERbeta inducible cells. E2
      increased psoriasin/S100A7 mRNA but cycloheximide treatment inhibited this
      effect. A relationship between ERbeta and psoriasin/S100A7 was observed in the
      p53 immunohistochemically negative subset of invasive breast tumors in-vivo (r =
      0.225, p = 0.046, n = 79). In conclusion we demonstrate that E2 induction of
      psoriasin/S100A7 can be specifically regulated through ERbeta in-vitro and
      associated with ERbeta in-vivo. These data support the hypothesis that
      psoriasin/S100A7 is specifically regulated by ERbeta activity and could be useful
      to guide future therapies targeting ERbeta in certain phenotypic subsets of
      breast cancers in-vivo.

PMID- 17009106
TI  - Ethnic and geographic differences in mammographic density and their association
      with breast cancer incidence.
AB  - The objective of this pooled analysis was to compare differences in dense areas
      and percent mammographic densities to breast cancer incidence in populations at
      different breast cancer risk. The data set included 1,327 women aged 40-80:
      Caucasians from Norway, Arizona, and Hawaii, Japanese from Hawaii and Japan,
      Latina from Arizona, and Native Hawaiians from Hawaii. One reader performed
      computer-assisted quantitative density assessment for all mammographic films.
      Multiple linear regression models evaluated the influence of the covariates on
      breast density. Spearman correlation coefficients (r (s)) estimated the
      association between breast density and breast cancer incidence for the seven
      populations. After adjustment for covariates, ethnicity, but not location, was
      significantly associated with breast density. In the full model, 19% of the
      variation in the dense areas and 46% in the variation of percent densities were
      explained by measured risk factors. Native Hawaiians had the largest dense areas
      and women in Japan the smallest, whereas percent densities were highest among
      Native Hawaiians and Japanese in Hawaii and lowest among Norwegian women. The
      mean age-adjusted dense area had the strongest association with breast cancer
      incidence (r (s) = 0.93, P = 0.003); the relation with percent density was
      considerably weaker (r (s) = 0.32, P = 0.48). The correlation between age
      adjusted dense area and breast cancer incidence remained strong after selectively
      removing individual data points. This comparison of mammographic densities
      suggests that, on a group level, age-adjusted dense areas may reflect breast
      cancer incidence better than percent densities.

PMID- 17009107
TI  - Health-related quality of life in long-term breast cancer survivors: nationwide
      survey in Denmark.
AB  - AIM: To investigate health-related quality of life (HRQOL) in a nationally
      representative sample of long-term breast cancer survivors (BCS) in Denmark.
      PARTICIPANTS AND METHODS: An age-stratified random sample of 2,000 female BCS >
      or = 5 years after primary surgery without recurrence was drawn from the Danish
      Breast Cancer Cooperative Group register, which is representative regarding long
      term BCS in Denmark, and compared with 3,104 women of the nationally
      representative Danish Health and Morbidity Survey 2000. The Short Form-36
      questionnaire assessed HRQOL and its association with BCS' sociodemography, type
      of surgery, systemic therapy, radiotherapy, time since operation, receptor
      status, and low/high risk protocol. RESULTS: The response rate was 79%. BCS
      tended to rate HRQOL better than the general female population. BCS reported
      significantly less "bodily pain" (P < 0.0001), better "general health" (P <
      0.0001), but worse "mental health" (P < 0.0001). Age interacted significantly
      with four other subscales (P < 0.05): Younger BCS reported worse HRQOL than
      equally aged women of the general population, while older BCS reported better
      HRQOL. Poor HRQOL was significantly associated with being single (all subscales:
      P < 0.05), short education (all subscales: P < 0.05, except "social function"),
      and high body mass index ("physical function", "role physical": P < 0.05). Breast
      cancer (low/high risk, receptor status) and treatment did not affect HRQOL.
      CONCLUSION: HRQOL was similar between BCS and women of the general population.
      Potential long-term effects of breast cancer (low/high risk, receptor status) and
      treatment did not seem to impact HRQOL. However, predictors for worse HRQOL in
      BCS were being single, and having a short education.

PMID- 17009108
TI  - Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant
      treated breast cancer survivors 5-10 years after chemotherapy.
AB  - PURPOSE: To explore the relationship of regional cerebral blood flow and
      metabolism with cognitive function and past exposure to chemotherapy for breast
      cancer. PATIENTS AND METHODS: Subjects treated for breast cancer with adjuvant
      chemotherapy remotely (5-10 years previously) were studied with neuropsychologic
      testing and positron emission tomography (PET), and were compared with control
      subjects who had never received chemotherapy. [O-15] water PET scans was acquired
      during performance of control and memory-related tasks to evaluate cognition
      related cerebral blood flow, and [F-18] fluorodeoxyglucose (FDG) PET scans were
      acquired to evaluate resting cerebral metabolism. PET scans were analyzed by
      statistical parametric mapping and region of interest methods of analysis.
      RESULTS: During performance of a short-term recall task, modulation of cerebral
      blood flow in specific regions of frontal cortex and cerebellum was significantly
      altered in chemotherapy-treated subjects. Cerebral activation in chemotherapy
      treated subjects differed most significantly from untreated subjects in inferior
      frontal gyrus, and resting metabolism in this area correlated with performance on
      a short-term memory task previously found to be particularly impaired in
      chemotherapy-treated subjects. In examining drug-class specific effects,
      metabolism of the basal ganglia was significantly decreased in tamoxifen +
      chemotherapy-treated patients compared with chemotherapy-only breast cancer
      subjects or with subjects who had not received chemotherapy, while chemotherapy
      alone was not associated with decreased basal ganglia activity relative to
      untreated subjects. CONCLUSION: Specific alterations in activity of frontal
      cortex, cerebellum, and basal ganglia in breast cancer survivors were documented
      by functional neuroimaging 5-10 years after completion of chemotherapy.

PMID- 17009109
TI  - Metaplastic carcinoma of the breast, an unusual disease with worse prognosis: the
      experience of the European Institute of Oncology and review of the literature.
AB  - BACKGROUND: Metaplastic carcinoma of the breast is a rare form of breast cancer
      and has an uncertain prognostic significance. The purpose of the present study
      was to compare the clinical course, and prognosis, between this type of tumor and
      poorly differentiated ductal carcinoma. PATIENTS AND METHODS: We analyzed 37
      cases of metaplastic carcinoma of the breast treated at our institution (European
      Institute of Oncology in Milan, Italy) between 1997 and 2004, comparing them with
      72 cases (control group) of poorly differentiated ductal carcinoma. All 109
      patients had negative receptors and were G3 at final histology. The control cases
      were matched according to year of surgery, pT (pT1 vs. pT2/3/4), and pN (absent
      vs. present). RESULTS: Of the 37 patients, eleven died from disease progression,
      eight developed metastatic disease and two experienced local recurrence. In the
      control group (72 patients) we observed three deaths due to disease progression,
      13 distant metastases, and two local recurrences. CONCLUSION: The overall
      survival in the metaplastic carcinoma group was significantly worse than in the
      control group. As regards to disease-free survival, there was no statistically
      significant difference between the two groups.

PMID- 17009110
TI  - Apology to the journal.

PMID- 17009111
TI  - Metastatic Crohn's disease of the face.

PMID- 17009112
TI  - The successful use of adalimumab to treat active Crohn's disease of an ileoanal
      pouch during pregnancy.

PMID- 17009113
TI  - Fentanyl or tramadol, with midazolam, for outpatient colonoscopy: analgesia,
      sedation, and safety.
AB  - The present study determined the acceptability of colonoscopy in outpatients
      treated with tramadol or fentanyl for analgesia and sedation. One hundred fifty
      patients were randomly assigned to receive midazolam, 0.05 mg/kg, and fentanyl, 2
      microg/kg, intravenously (group 1), midazolam, 0.05 mg/kg, and tramadol, 1 mg/kg,
      per os (group 2), or midazolam, 0.05 mg/kg, and tramadol, 2 mg/kg, per os (group
      3). Pain severity, level of sedation, cardiorespiratory parameters, and procedure
      related side effects and complications were registered and analyzed. No
      significant cardiorespiratory disturbances were observed. Sedation level during
      the procedure was similar in all groups. Pain severity values measured during the
      procedure was significantly higher in groups 2 and 3 than in group 1 (P < 0.001).
      Both hospital and home adverse events occurred more frequently in groups 2 and 3
      compared to group 1 (P < 0.03). The patients receiving fentanyl-based analgesia
      tolerated colonoscopy better than patients treated with tramadol.

PMID- 17009114
TI  - Factors contributing to patient nonattendance at open-access endoscopy.
AB  - Patients who miss endoscopy appointments cause inefficient utilization of medical
      resources. Because national nonattendance rates are as high as 27% and reasons
      for nonattendance have not been well studied, we sought to quantitate
      nonattendance at our tertiary care institution. We conducted a retrospective
      records review of the institutional database to identify patients who did not
      attend a scheduled endoscopy appointment between January 2000 and December 2003.
      Nonattendance was defined as either not showing up for an appointment or
      canceling it on the day it was scheduled. At our institution, patient care
      assistants contact such patients to document their reasons in the database. Of
      36,480 patients scheduled for outpatient endoscopy, 1,490 (4.1%) did not show up
      because of either facility-related (44.3%; e.g., scheduling errors) or patient
      related (55.7%; e.g., noncancellation, illness, or hospitalization) reasons. Our
      4.1% nonattendance rate over 4 years is considerably lower than that reported by
      other endoscopy centers.

PMID- 17009115
TI  - Rose hip and Lactobacillus plantarum DSM 9843 reduce ischemia/reperfusion injury
      in the mouse colon.
AB  - Ischaemia/reperfusion (I/R) of the colon is an inflammatory condition that leads
      to tissue injury where reactive oxygen species play a central role. Rose hip is
      rich in biologically active polyphenols with antioxidative properties, which may
      be important in prevention of lipid peroxidation. L. plantarum DSM 9843 possesses
      enzymatic activity towards polyphenols. The objective of this study was to define
      the effect of oral administration of L. plantarum and rose hip in I/R injury.
      Administration of rose hip and L. plantarum significantly decreased MDA levels in
      caecum tissue and Enterobacteriaceae counts in caecum stool. A positive
      correlation between MDA levels and Enterobacteriaceae counts was found. The
      results support a synergistic/additive role of rose hip and L. plantarum in
      reducing lipid peroxidation. Therefore rose hip and L. plantarum may be used as a
      pretreatment to tissue injuries, e.g. colonic surgery, organ transplantation and
      vascular surgery.

PMID- 17009116
TI  - Role of serum tumor markers in monitoring for recurrence of gastric cancer
      following radical gastrectomy.
AB  - It has been suggested that the serum tumor markers AFP, CEA, and CA19-9 may serve
      as prognostic factors or indicators for recurrence after radical gastrectomy for
      gastric cancer. We compared the value of these markers in a group with (n=52) and
      a group without recurrent gastric cancer (n=52) according to the site of
      recurrence. Serum levels of tumor markers were measured at the time of
      preoperative diagnosis and at follow-up. At least one tumor marker was positive
      preoperatively in 20 with recurrence vs. 7 controls (p=0.007). The peritoneum was
      the most common recurrent site. The positive predictive value of AFP was high at
      the time of diagnosis and CA19-9 positivity was high at the time of recurrence.
      Positive CEA suggested recurrence to the liver. In summary, an elevated tumor
      marker at diagnosis or during follow up may identify patients at higher risk for
      a recurrence. CA19-9 may be especially useful as a marker for peritoneal
      recurrence of the gastric cancer, and CEA for recurrence to liver.

PMID- 17009117
TI  - Aspects of digestive tract tumors in Down syndrome: a literature review.
AB  - The purpose of this study was to describe the digestive neoplasms found in
      persons with Down syndrome. Due to intellectual disability, persons with Down
      syndrome do not convey their symptoms and pain, leading to delayed diagnosis and
      potentially worse outcome. It is thus important to know which organs are at risk
      for tumors and possible tumor risk factors. In a review of the literature, we
      found 13 benign tumors and 127 cancers in 1 fetus, 8 children, and 131 adults
      with Down syndrome. The review suggests a decreased incidence of digestive
      cancer, however, with a possible increased incidence of neoplasms of the pancreas
      and gallbladder. The distribution of cancers is distinct from that in the general
      population and that in persons with other intellectual disabilities who share the
      same life conditions, suggesting that constitutional protective factors exist.
      This review may allow a more specific, adapted medical follow-up for persons with
      Down syndrome and could help to elucidate the oncogenesis of digestive neoplasms.

PMID- 17009118
TI  - Role of matrix metalloproteinase-7 in colorectal adenomas.
AB  - Matrix metalloproteinases (MMPs) degregade and remodel the extracellular matrix.
      They are known to be overexpressed as normal mucosa progresses to adenomas and
      carcinomas. In our prospective study we measured the overexpression of MMP-7
      immunohistochemically in various types of colonic adenomas. Although MMP-7 has
      already been shown to be overexpressed in various types of colonic adenomas,
      tubular versus villous adenomas had not been further seperated to date. Seventy
      six patients had either normal mucosa (n=15) or tubular (n=32), tubulovillous
      (n=16), or villous (n=13) colonic adenoma. MMP-7 expression was classified into
      three categories, as negative, weakly stained, or strongly stained, depending on
      the percentage of cells stained. Each adenoma was graded according to the
      percentage of strongly stained areas in the adenoma as G0, G1, G2, or G3. Sixty
      nine percent of villous adenomas showed grade 3 staining of MMP-7, versus none of
      the tubular adenomas. G0 and G1 staining was not detected in the villous
      adenomas. The results of the study show that the degrees of overexpression of the
      three subtypes of colonic adenomas were statistically significantly different. In
      conclusion, MMP-7 overexpression is thought to be an early event in the adenoma
      carcinoma pathway.

PMID- 17009119
TI  - Abnormal expression of the peptide transporter PepT1 in the colon of massive
      bowel resection rat: a potential route for colonic mucosa damage by transport of
      fMLP.
AB  - The aim of this study was to investigate the effect of abnormal intestinal
      oligopeptide transporter (PepT1) on rat colon inflammation by transportion of N
      formyl-methionyl-leucyl-phenylalanine (fMLP). We induced upregulation of PepT1 in
      the colon of rats by 80% small bowel resection and examined colonic PepT1 di
      tripeptide transport activity. By Western blot analysis, PepT1 was clearly
      detected in the colon of bowel resection rats, while it was absent from the colon
      of bowel transection and reanastomosis rats. The experiment with cephalexin colon
      perfusion showed that the arterial cephalexin concentration in resection rats was
      five to nine times that in transection rats. Inhibition of PepT1 by Gly-Gly
      completely abolished cephalexin absorption from the colon of resection rats. We
      found that 10 microM fMLP perfusion in the colon of resection rats for 4 hr
      significantly increased myeloperoxidase (MPO) activity and caused colon wall
      damage. In contrast, 10 muM fMLP perfusion in the colon of transection rats did
      not induce any inflammation. A 5 mM Gly-Gly perfusion completely inhibited the
      MPO activity and colonic wall damage induced by 10 muM fMLP. We conclude that
      colonic PepT1 induced by bowel resection may provide a mechanism for oligopeptide
      transport and may serve as a potential cause of colonic mucosa damage by
      transport of the bacterial product fMLP in rat colon.

PMID- 17009120
TI  - The frontiers of reflux disease.
AB  - Gastroesophageal reflux disease has frequently been implicated in a wide variety
      of complications beyond the esophagus. These so-called "extraesophageal"
      disorders range from diseases of the respiratory tract, such as asthma and
      bronchitis, to more remote sites and conditions such as otitis and dental
      erosion. Many articles proposing a link between reflux disease and a multitude of
      extraesophageal complications have been published, but indisputable evidence that
      these conditions are caused by reflux disease is rare. Much of the support for a
      link between reflux disease and a number of extraesophageal complications is
      based on the observation that reflux disease frequently coexists with other
      disorders. A causal link is difficult to prove, however, and this review aims to
      critically evaluate the available evidence, looking, where possible, at
      longitudinal studies, expert diagnoses, and response to acid-suppressive therapy
      as a means of determining the true relationship between GERD and its putative
      extraesophageal complications.

PMID- 17009121
TI  - Allergen-specific in vitro cytokine production in adult patients with
      eosinophilic esophagitis.
AB  - Although the pathogenesis of eosinophilic esophagitis (EE) likely involves
      hypersensitivity reactions against exogenous allergens, allergen-specific
      cellular immune responses have not been studied. We investigated allergen-induced
      cytokine production by peripheral blood mononuclear cells (PBMCs) in adult
      patients with EE (n=15) and healthy controls (HC; n=9). PBMCs were incubated with
      nine common food and environmental allergens or a nonspecific mitogen, and the
      levels of interleukin (IL)-5, IL-10, IL-13, and interferon-gamma in the cell-free
      supernatants were determined. Spontaneous and mitogen-stimulated cytokine
      production did not differ between EE and HC. House dust mite, ragweed,
      Aspergillus, milk, and soy induced significantly higher IL-5 production in EE (P
      < 0.05). House dust mite also augmented IL-13 production in EE (P < 0.05).
      Furthermore, PBMCs from three EE patients without allergen-specific IgE
      vigorously produced IL-5 and IL-13 on allergen stimulation. Thus, immune
      responses in EE are characterized by enhanced production of Th2-like cytokines
      against both food and environmental allergens.

PMID- 17009122
TI  - Who benefited from an efficacious intervention for youth living with HIV: a
      moderator analysis.
AB  - An efficacious intervention that results in young people living with HIV (YPLH)
      reducing their transmission risk has been identified. The present study
      identifies who is most likely to benefit from the intervention. Regression models
      were used to examine whether background contextual factors moderated the
      intervention's success. Percentage of protected sex was moderated by ethnicity,
      use of antiretroviral medications (ARV), healthcare utilization and mental
      health. Number of partners was moderated by anxiety and depression. When deciding
      if an intervention is appropriate and beneficial for an individual young person,
      consideration must be given to type of services the youth currently accesses and
      the youth's mental health.

PMID- 17009123
TI  - Epidemiological associations between gambling behavior, substance use & mood and
      anxiety disorders.
AB  - OBJECTIVE: To compare gambling behaviors in a random sample of community
      residents with and without mental disorders identified by the Composite
      International Diagnostic Interview (CIDI). METHOD: A large national community
      survey conducted by Statistics Canada included questions about problems arising
      from gambling activities as per the Canadian Problem Gambling Index (CPGI). We
      compared respondents within three gambling severity categories (non-problem, low
      severity and moderate/high severity gambling) across three diagnostic groupings
      (mood/anxiety disorders, substance dependence/harmful alcohol use, no selected
      psychiatric disorder). RESULTS: Of the 14,934 respondents age 18-64 years who
      engaged in at least one type of gambling activity in the previous 12 months, 5.8%
      fell in the low severity gambling category while 2.9% fell in the moderate/high
      severity category. Females accounted for 51.7% of the sample. The risk of
      moderate/high severity gambling was 1.7 times higher in persons with mood or
      anxiety disorder compared to persons with no selected disorder. For persons with
      substance dependence or harmful alcohol use, the risk of moderate/high severity
      gambling was 2.9 times higher. Persons with both mood/anxiety and
      substance/alcohol disorders were five times more likely to be moderate/high
      severity gamblers. The odds ratio for females was 0.6 and for those with less
      than post-secondary education it was 1.52. Differences in age and personal income
      were not significant. CONCLUSIONS: Individuals in the community suffering from
      mood/anxiety disorders and substance dependence/harmful alcohol, and especially
      those with both, experience a higher risk for gambling problems. The treatment of
      these comorbidities should be integrated into any problem gambling treatment
      program.

PMID- 17009124
TI  - A psychometric evaluation of the DSM-IV pathological gambling diagnostic
      criteria.
AB  - Specific diagnostic criteria for pathological gambling (PG) have been available
      for 25 years, since the publication of DSM-III. Little research has examined the
      psychometric performance of the diagnostic criteria. The goal of the present
      report from the Rhode Island Methods to Improve Diagnostic Assessment and
      Services (MIDAS) project was to examine the sensitivity, specificity and
      predictive values of the DSM-IV PG criteria for psychiatric outpatients who
      screened positive for a gambling problem. A total of 1709 psychiatric outpatients
      were evaluated with a semistructured diagnostic interview for PG. Of all patients
      88 screened positive for PG, 40 of whom met DSM-IV diagnostic criteria for a
      lifetime history of PG. All ten DSM-IV criteria were significantly more frequent
      in the PG group. The sensitivity of the criteria ranged from 25.0% to 90.0% (mean
      = 67.8%), whereas specificity ranged from 62.5% to 100% (mean = 81.9%). Positive
      predictive values ranged from 64.1% to 100% (mean = 78.9%), and negative
      predictive values ranged from 61.5% to 90.7% (mean = 77.1%). Guidelines are
      recommended for determining whether a diagnostic criterion should be retained as
      part of the set of diagnostic criteria, and our results suggested that two of the
      DSM-IV PG criteria are candidates for elimination (criterion 8--commitment of
      illegal acts; criterion 10--reliance on others for financial assistance to
      relieve a desperate financial problem).

PMID- 17009125
TI  - Evolution of growth hormone in primates: the GH gene clusters of the New World
      monkeys marmoset (Callithrix jacchus) and white-fronted capuchin (Cebus
      albifrons).
AB  - The GH gene cluster in marmoset, Callithrix jacchus, comprises eight GH-like
      genes and pseudogenes and appears to have arisen as a consequence of gene
      duplications occurring independently of those leading to the human GH gene
      cluster. We report here the complete sequence of the marmoset GH gene locus,
      including the intergenic regions and 5' and 3' flanking sequence, and a study of
      the multiple GH-like genes of an additional New World monkey (NWM), the white
      fronted capuchin, Cebus albifrons. The marmoset sequence includes 945 nucleotides
      (nt) of 5' flanking sequence and 1596 nt of 3' flanking sequence that are
      "unique"; between these are eight repeat units, including the eight GH
      genes/pseudogenes. The breakpoints between these repeats are very similar,
      indicating a regular pattern of gene duplication. These breakpoints do not
      correspond to those found in the much less regular human GH gene cluster. This
      and phylogenetic analysis of the repeat units within the marmoset gene cluster
      strongly support the independent origin of these gene clusters, and the idea that
      the episode of rapid evolution that occurred during GH evolution in primates
      preceded the gene duplications. The marmoset GH gene cluster also differs from
      that of human in having fewer and more evenly distributed Alu sequences (a single
      pair in each repeat unit) and a "P-element" upstream of every gene/pseudogene. In
      human there is no P-element upstream of the gene encoding pituitary GH, and these
      elements have been implicated in placental expression of the other genes of the
      cluster. The GH gene clusters in marmoset and capuchin appear to have arisen as
      the consequence of a single-gene duplication event, but in capuchin there was
      then a remarkable expansion of the GH locus, giving at least 40 GH-like genes and
      pseudogenes. Thus even among NWMs the GH gene cluster is very variable.

PMID- 17009126
TI  - On the origins of a crowded cytoplasm.
AB  - Contemporary cells show a highly crowded macromolecular content, the processes
      which originated this state being largely unknown. We propose that a driving
      force leading to the crowded cellular state could be the increase in growth rate
      produced by an enhanced cytoplasmic protein concentration. Briefly, in a diluted
      scenario, an increase in protein concentration has two opposing effects on growth
      rate. The favorable effect is the increase in the activity per unit volume of the
      component proteins and the disadvantageous effect is the concomitant increase in
      the protein mass per unit volume which has to be produced. In this work we show
      that the first effect is quantitatively more important, resulting in an overall
      increase in growth rate. This result was obtained with a model of E. coli and
      using nonmechanistic physiological arguments. The proposed driving force operates
      even at low protein concentrations, where the nonspecific interactions of
      macromolecular crowding are not significant, and could be as ancient as the first
      protocells. Experimental measurement of this cytoplasmic protein concentration
      effect in present organisms is hindered by the prevailing nonspecific
      interactions, product of long-term evolution. However, chemical/biochemical
      systems, built up to mimic properties of living cells, could be an adequate tool
      to test this effect.

PMID- 17009128
TI  - Modified Japanese medaka embryo-larval bioassay for rapid determination of
      developmental abnormalities.
AB  - The Japanese medaka (Oryzias latipes) early-life-stage bioassay (18-day test)
      provides a suitable laboratory model for the evaluation of toxicant impact. The
      naturally high variability in the time to hatch for medaka embryos is, however, a
      major limitation in terms of the duration of the test. In this study, the 18-day
      test was modified to use agitation to synchronize hatch and reduce time to hatch
      for nonexposed embryos. Then, bioassays were conducted using two different
      complex mixtures (polycyclic aromatic hydrocarbons (PAHs) and naphthenic acids
      (NAs)) to compare the sensitivity of the measurement endpoints using the 18-day
      standard protocol (SP) and the modified protocol (MP). Agitation reduced time to
      hatch by one third or more and improved hatch success (100%). The MP proved to be
      a more sensitive test method for the sublethal evaluation of a stressor (PAH
      mixture) that caused reduced hatch length and induced signs of blue sac disease
      (BSD) including heart deformities, yolk sac-pericardial edema, and cranial
      skeletal deformities. In contrast, there was some variability in the sensitivity
      of the test methods for developmental endpoints for the sublethal evaluation of a
      stressor (NA mixture) that had no effect on hatch length and was a weak inducer
      of signs of BSD. Even though the sensitivity of the measurement endpoints were
      slightly more or less sensitive for the MP vs. SP depending on the mixture
      tested, the MP using agitation is recommended as a cost-effective and rapid
      alternative for screening the sublethal impact of toxicants on the early-life
      stages of fish.

PMID- 17009127
TI  - Cd exposures in fathead minnows: effects on adult spawning success and
      reproductive physiology.
AB  - The primary objective of this study was to determine whether cadmium (Cd)
      exposures alter reproduction in fathead minnows (Pimephales promelas). Pairs of
      sexually mature minnows were exposed to waterborne Cd at 0, 12.5, 25, or 50
      microg/L for 21 days. During this exposure period, the reproductive success of
      pairs was assessed. Following the exposure, gonadosomatic index (GSI), male
      secondary sexual characteristics, male plasma 11-ketotestosterone (11-KT)
      concentrations, and female plasma estradiol (E2) concentrations were determined.
      Results of this study show that Cd exposures impair reproduction in fathead
      minnows. Pairs exposed to 50 microg/L experienced a significant decline in
      spawning frequency and fecundity relative to unexposed minnows. Cd exposures also
      caused alterations in male secondary sexual characteristics, as males exposed to
      25 microg/L had significantly fewer nuptial tubercles than controls. Furthermore,
      males exposed to 12.5 microg/L Cd experienced a significant increase in plasma 11
      KT concentrations relative to controls. No alterations in GSI or female plasma E2
      concentrations were observed.

PMID- 17009129
TI  - Environmental contaminants in fish and their associated risk to piscivorous
      wildlife in the Yukon River Basin, Alaska.
AB  - Organochlorine chemical residues and elemental contaminants were measured in
      northern pike (Esox lucius), longnose sucker (Catostomus catostomus), and burbot
      (Lota lota) from 10 sites in the Yukon River Basin (YRB) during 2002. Contaminant
      concentrations were compared to historical YRB data and to toxicity thresholds
      for fish and piscivorous wildlife from the scientific literature. A risk analysis
      was conducted to screen for potential hazards to piscivorous wildlife for
      contaminants that exceeded literature-based toxicity thresholds. Concentrations
      of total DDT (sum of p,p'-homologs; 1.09-13.6 ng/g), total chlordane (0.67-7.5
      ng/g), dieldrin (<0.16-0.6 ng/g), toxaphene (<11-34 ng/g), total PCBs (<20-87
      ng/g), TCDD-EQ (<or=1.7 pg/g), arsenic (0.03-1.95 microg/g), cadmium (<0.02-0.12
      microg/g), copper (0.41-1.49 microg/g), and lead (<0.21-0.27 microg/g) did not
      exceed toxicity thresholds for growth and reproduction in YRB fish.
      Concentrations of mercury (0.08-0.65 microg/g), selenium (0.23-0.85 microg/g),
      and zinc (11-56 microg/g) exceeded toxicity thresholds in one or more samples and
      were included in the risk analysis for piscivorous wildlife. No effect hazard
      concentrations (NEHCs) and low effect hazard concentrations (LEHCs), derived from
      literature-based toxicity reference values and avian and mammalian life history
      parameters, were calculated for mercury, selenium, and zinc. Mercury
      concentrations in YRB fish exceeded the NEHCs for all bird and small mammal
      models, which indicated that mercury concentrations in fish may represent a risk
      to piscivorous wildlife throughout the YRB. Low risk to piscivorous wildlife was
      associated with selenium and zinc concentrations in YRB fish. Selenium and zinc
      concentrations exceeded the NEHCs and LEHCs for only the small bird model. These
      results indicate that mercury should continue to be monitored and assessed in
      Alaskan fish and wildlife.

PMID- 17009130
TI  - Dietary Pb accumulation in juvenile freshwater rainbow trout (Oncorhynchus
      mykiss).
AB  - Three different diets amended with lead (Pb) nitrate Pb(NO3)2 (7, 77, and 520
      microg Pb/g dry weight) and a Pb-free control diet (0.06 microg Pb/g dry weight)
      were fed to juvenile freshwater rainbow trout for 21 days. Accounting for
      measured food consumption, the calculated doses per fish were 0.02, 3.7, 39.6,
      and 221.5 microg/day, for the control, low, intermediate, and high Pb treatments,
      respectively. The patterns of Pb accumulation over time were determined in
      various tissues (gills, liver, kidney, intestine, carcass), red blood cells
      (RBC), and plasma, as well as feeding, growth, hematological, and ionoregulatory
      parameters. Pb accumulation occurred in a dose-dependent manner in all tissues
      except the plasma, where accumulation was minimal. Overall, when fed the highest
      Pb diet, the intestine exhibited the greatest Pb burden (17.8 microg Pb/g tissue
      wet weight), with high concentrations also found in the kidney (2.4 microg Pb/g
      tissue wet weight) and liver (1.9 microg Pb/g) at the highest dietary Pb
      treatment by day 21. The RBCs accumulated a substantial amount of Pb (1.5 microg
      Pb/g) when compared to the plasma (0.012 microg Pb/g) in the high treatment
      group. The percentage of Pb retained in the fish decreased with increasing
      dietary Pb concentrations. Growth, survival, plasma protein, and hematocrit were
      not significantly affected by dietary Pb. Plasma Ca2+ levels decreased at the
      beginning of the experiment, whereas Mg2+ levels decreased during the middle of
      the experiment in both the intermediate and high dietary treatments. Both the
      Ca2+ and Mg2+ levels stabilized by day 21. Branchial Ca2+ and Na+ influx rates
      were not affected by dietary Pb, except on day 8 where Na+ influx rates were
      significantly elevated. The results of this study show that Pb does accumulate
      internally from the diet when present at levels within the range reported in
      contaminated benthic invertebrates in nature. We further identify the intestine
      as a potential target site of chronic toxicity of Pb via the diet, and RBCs as a
      reservoir of dietary Pb.

PMID- 17009131
TI  - The effect of paraquat on hepatic EROD activity, liver, and gonadal histology in
      males and females of Nile tilapia, Oreochromis niloticus, exposed at different
      temperatures.
AB  - The activity of fish monooxygenases has been used as a monitoring tool to
      evaluate contamination by cytochrome P450 inducing agents. In this study
      ethoxyresorufin O-deethylase (EROD) activity was analyzed in males and females of
      Nile tilapia exposed to a low concentration of paraquat (PQ) at 17 degrees C and
      27 degrees C. PQ-treated fish showed a high hepato-somatic index, except females
      acclimated at 17 degrees C. No differences were found for the gonado-somatic
      index (GSI) between males. However, PQ-treated females showed high GSI values
      (6.46+/-1.75) when compared with the control group (2.30+/-0.26) maintained at 27
      degrees C. Males and females exposed to PQ showed higher microsomal protein
      values than the control group (9.46+/-0.22 vs. 6.20+/-0.18 at 17 degrees C;
      9.51+/-0.35 vs. 4.70+/-0.19 mg of protein at 27 degrees C, in PQ-treated and
      control groups, respectively). The EROD activity was high in females exposed to
      PQ when compared with the control group at 17 degrees and 27 degrees C. The liver
      histology showed that PQ also caused some hepatic alterations of parenchyma, like
      vacuolization, necrosis, and an increase of macrophages aggregates and
      eosinophilic granular cells. Females exposed to PQ showed a greater increase of
      late-vitellogenic (22.2+/-3.2) and mature (12.1+/-2.0) percentage of oocytes than
      the control group (9.9+/-3.0 and 8.0+/-4.3, respectively), and a lower percentage
      of primary oocytes (8.0+/-3.3) at 27 degrees C. In short, this work has advanced
      new knowledge on the influence of gender in biotransformation activity and the
      reproductive activity of Nile tilapia exposed to a low concentration of paraquat,
      and demonstrated that their effects could be observed at different temperatures.

PMID- 17009132
TI  - Simultaneous Cd2+, Zn2+, and Pb2+ uptake and accumulation by photosynthetic
      Euglena gracilis.
AB  - The ability of Euglena gracilis to simultaneously remove and accumulate Zn2+,
      Cd2+, and Pb2+ from culture up- to media was evaluated. E. gracilis was able to
      remove up to 80% of the Cd2+ present in the medium when cultured with 20 or 50
      microM CdCl2. Higher external Cd2+ concentrations increased Cd2+ accumulation per
      cell but decreased cell growth, thus decreasing the capacity of the cell culture
      to remove Cd2+. E. gracilis removed 70% to 80% of the Zn2+ present in the medium
      when cultured with 5 to 50 microM ZnSO4. Zn2+ did not affect Cd2+ removal
      capacity. E. gracilis was much less efficient in removing Pb2+ (<15%) when
      cultured with 100 or 200 microM Pb(NO3)2. Moreover, Pb2+ decreased the efficiency
      to remove Cd2+, but it did not affect Zn2+ removal. Cd2+ induced a generalized
      increase in the cellular thiol compounds, including phytochelatins, and Pb2+ had
      an additive effect only at 200 microM. Zn2+ did not stimulate phytochelatin
      synthesis. Cd2+ and Pb2+ colocated in the same cytosolic high-molecular-weight
      fraction. Because Pb2+ is a weak phytochelatin inducer, competition between Pb2+
      and Cd2+ for transportation across the plasma membrane and binding to
      phytochelatins and other thiol compounds is proposed to explain the detrimental
      effects of Pb2+ on the Cd2+ removal capacity of E. gracilis.

PMID- 17009133
TI  - Short scar vertical mammaplasty marking using the Wise pattern.

PMID- 17009134
TI  - Treatment of small congenital nevocellular naevi using a combination of
      ultrapulse carbon dioxide laser and Q-switched frequency-doubled Nd-YAG laser.
AB  - This report describes treatment combining Ultrapulse CO(2) laser and Q-switched
      frequency-doubled neodymium:yttrium-aluminum-garnet (Nd-YAG) laser for a number
      of congenital nevocellular naevi (CNN). The Ultrapulse CO(2) laser removes the
      superficial component, which contains most of the color, preserving the integrity
      of the reticular dermis. At a later stage, any residual color is targeted using
      the Nd-YAG laser. To date, a total of 10 histologically proven CNNs have been
      treated at the Laser Suite. The median age of the patients was 18 years (range,
      13-24 years). All the patients were white females. The patients accepted for
      treatment had relatively small lesions (mean surface area, 352 mm(2); range, 50
      1,092 mm(2)), but the lesions were either cosmetically sensitive or located in an
      anatomically critical area in which excision could result in a scar that would be
      unpredictable. The median follow-up period was 24 months. The overall results
      have been satisfactory, with reduction of color and no significant scarring. The
      minor textural and pigmentary changes were acceptable to the patients.

PMID- 17009136
TI  - Improving the lateral fullness of the upper eyelid.
AB  - The lateral fullness of the upper eyelid is its convex surface area from the
      eyebrow to the eyelid crease. Rejuvenation of upper eyelids can be achieved by
      accenting their fullness. An S-shaped fusiform skin segment is removed from the
      upper eyelid, with care taken to spare the orbicularis occuli muscle.
      Approximately 1 ml of fat tissue is excised from the medial compartment by
      transmuscular incision. The fat is placed in the crease, and the orbicularis
      occuli muscle is stitched together over the transplanted fat tissue. Imbrication
      of the orbicularis occuli muscle and insertion of 1 ml of fat tissue into the
      muscle layers increase the lateral fullness and significantly emphasizes the
      aesthetic result of upper eyelid blepharoplasty.

PMID- 17009137
TI  - Applicability of the Milan criteria for determining liver transplantation as a
      first-line treatment for hepatocellular carcinoma.
AB  - BACKGROUND: To determine whether or not the Milan criteria (MC) should be used to
      determine the applicability of liver transplantation (LT) as a first-line
      treatment for patients with cirrhosis with hepatocellular carcinoma (HCC) who are
      able to endure hepatectomy. METHODS: Retrospective analysis of 82 patients with
      cirrhosis with HCC who were treated by hepatectomy without LT at our institution
      between 1990 and 2003. RESULTS: Of these 82 patients, 48 met the MC. Proportional
      hazard regression analyses to determine the independent prognostic factors for
      postoperative cumulative patient and disease-free survival showed that meeting
      the MC is the strongest prognostic factor for both patient and disease-free
      survival. The cumulative patient and disease-free survival rates were 76.7% and
      28.9%, respectively, at 5 years in patients who met the MC. The cumulative
      disease-free survival was markedly inferior to those in previously reported
      series of LT for HCC who met the MC, but the cumulative patient survival was
      comparable to those in the previously reported series. A comparison of cumulative
      postoperative survival between patients who met the MC and fulfilled all five
      factors listed below and patients who met the MC but did not fulfill any of the
      five factors demonstrated that the latter patients showed statistically
      significantly worse postoperative patient survival than the former. The five
      factors included: Model for End-Stage Liver Disease score < 10, indocyanine green
      retention rate at 15 minutes < 20%, absence of microscopic fibrous capsular
      invasion and microscopic intrahepatic metastases, and earlier grade (T1 or T2) of
      American Joint Committee on Cancer tumor classification. CONCLUSIONS: The MC
      should not be used to determine the applicability of LT as a first-line treatment
      for patients with HCC considered able to endure hepatectomy. However, modifying
      MC with some clinicopathological factors could satisfy the appropriate criteria
      for applying LT as a first-line treatment for these patients.

PMID- 17009138
TI  - Image-guided oncologic surgery using invisible light: completed pre-clinical
      development for sentinel lymph node mapping.
AB  - BACKGROUND: Invisible near-infrared (NIR) fluorescent light permits high
      sensitivity, real-time image-guidance during oncologic surgery without changing
      the look of the surgical field. In this study, we complete pre-clinical
      development of the technology for sentinel lymph node (SLN) mapping using a large
      animal model of spontaneous melanoma. METHODS: Sinclair swine with spontaneous
      melanoma metastatic to regional lymph nodes were used because of their similarity
      to human melanoma. Organic lymphatic tracers tested included FDA-approved
      indocyanine green adsorbed non-covalently to human serum albumin (HSA), and NIR
      fluorophore CW800 conjugated covalently to HSA (HSA800). The inorganic/organic
      hybrid tracer tested was type II NIR quantum dots with an anionic coating.
      Primary tumors received four peri-tumoral injections of each tracer, with a
      fluorophore dose of 100 pmol to 1 nmol per injection. SLN mapping and image
      guided resection were performed in real-time. RESULTS: Each of the 3 lymphatic
      tracers was injected into n = 4 separate primary melanomas in a total of 6
      animals. All 12 injections resulted in identification of the SLN(s) and their
      associated lymphatic channels within 1 minute in 100% of cases, despite highly
      pigmented skin and black fur. Hydrodynamic diameter had a profound impact on
      tracer behavior in vivo. CONCLUSIONS: This study completes the pre-clinical
      development of NIR fluorescence-guided SLN mapping and provides insight into
      imaging system optimization and tracer choice for future human clinical trials.
      The technology is likely to eliminate the need for radioactive and colored
      tracers, permits real-time image guidance throughout the procedure, and assists
      the pathologist in tissue analysis.

PMID- 17009139
TI  - A dangerous liaison--pheochromocytoma in patients with malignant disease.
AB  - BACKGROUND: Adrenal masses in patients with known malignancy may be interpreted
      as metastasized disease, although a significant proportion of these tumors are of
      adrenal origin. Despite improved imaging techniques, it remains difficult to
      distinguish an adrenal metastasis from a pheochromocytoma or a lipid-poor
      adrenocortical adenoma. PATIENTS AND METHODS: We report a case series of four
      patients with established or suspected malignant disease (melanoma, transitional
      cell carcinoma and prostate carcinoma, thyroid carcinoma, colorectal carcinoma)
      harboring an adrenal mass. None of these patients showed clinical symptoms
      indicative for a pheochromocytoma. RESULTS: Surgery unrelated to the adrenal
      lesion (n = 3) or biopsy of the adrenal mass (n = 1) was performed without prior
      endocrine work-up. Pronounced hemodynamic instability including hypertensive
      crisis was observed during surgery in all patients. In contrast, in the same
      patients preoperative alpha-blockade with phenoxybenzamine and an increased
      awareness of the potential risks led to improved hemodynamic stability following
      adrenalectomy for pheochromocytoma. CONCLUSION: Our series is a strong reminder
      of the risks associated with surgery in patients harboring an unsuspected
      pheochromocytoma and underscores the need to exclude a pheochromocytoma in all
      patients with an adrenal mass and without a definitive diagnosis of the mass,
      especially when they are scheduled for surgery or adrenal biopsy. Otherwise, life
      threatening hypertensive crisis can be precipitated even in the previously
      asymptomatic patient.

PMID- 17009140
TI  - Sonographically guided fine needle aspiration with rapid parathyroid hormone
      assay.
AB  - BACKGROUND: Persistent or recurrent primary hyperparathyroidism (1 degrees HPTH)
      is ideally treated with limited dissection, based on accurate localization, to
      minimize operative risks. To accurately localize parathyroid tissue, we employed
      ultrasound-guided fine needle aspiration (US FNA) with an on-site rapid
      parathyroid hormone (PTH) assay to confirm localization. METHODS: Of the 272
      patients evaluated for 1 degrees HPTH, 34 had persistent or recurrent disease.
      Standard localization was equivocal in 12, who were referred for US FNA.
      Suspicious tissue was identified on US and FNA was performed. Analysis with a
      rapid PTH assay provided on-site result within 12 min. Patients were monitored
      clinically, and then discharged after observation. RESULTS: Twelve patients were
      referred for US FNA; eight were female. Ten patients had persistent disease, one
      had recurrent, and one had 1 degrees HPTH following thyroidectomy. Two of the 12
      were excluded due to negative ultrasound examination. Of the remaining ten,
      positive aspirates were found in nine, and seven proceeded to surgery. In six
      patients there was 100% correlation between sonographic and operative findings.
      The remaining patient had no identifiable adenoma, but PTH normalized after
      arterial ligation. All patients received a limited directed surgical approach,
      employing cervical block anesthesia in three. Four were discharged on the day of
      surgery and all were cured. There was one infectious complication of US FNA.
      CONCLUSIONS: The use of rapid PTH assay can be effectively utilized for
      localization of parathyroid tissue in remedial parathyroid surgery. Confirmation
      of localization markedly improves subsequent surgery and allows selective use of
      minimally invasive techniques.

PMID- 17009141
TI  - Bypass surgery versus palliative pancreaticoduodenectomy in patients with
      advanced ductal adenocarcinoma of the pancreatic head, with an emphasis on
      quality of life analyses.
AB  - BACKGROUND: In some centers, palliative resection (PR; partial
      pancreaticoduodenectomy) is, in selected cases, promoted in preference to double
      loop bypass (DLB) surgery for advanced pancreatic cancer. This prospective study
      compares PR with DLB, placing particular focus on patients' quality of life
      (QoL). METHODS: From 01/1993 to 09/2004, 167 patients were analyzed in a
      prospective single center study of palliative surgical treatment of advanced
      ductal adenocarcinoma of the pancreatic head. Thirty-eight underwent PR and 129
      underwent palliative DLB. Patients undergoing DLB were divided into: (1) locally
      advanced disease (LAD-subgroup; n = 61; 47%) and (2) metastasized disease (MD
      subgroup; n = 68; 53%). QoL was assessed using the EORTC QLQ-C30 questionnaire
      supplemented by a pancreatic cancer specific module. QoL data were collected pre
      operatively and for up to 12 months after surgery. RESULTS: Median survival was
      7.0 months (95% CI 4.09; 9.91) in PR patients and 6.0 months (95% CI 5.39; 6.61)
      in patients who received DLB. Mortality and morbidity were, respectively, 7.8 and
      58% for PR, and 2.6 and 42% for DLB. QoL decreased more after PR than after DLB.
      The DLB-group recovered quicker, reaching pre-operative QoL levels after 3
      months, and were less impaired when discharged. The LAD-subgroup and the MD
      subgroup presented with equal levels of QoL. CONCLUSIONS: QoL analysis revealed
      favorable QoL data after DLB. Additionally, the survival rates of the two groups
      did not differ significantly, but morbidity and mortality rates in the PR group
      were elevated. Therefore, the use of PR for advanced pancreatic cancer needs to
      be carefully evaluated.

PMID- 17009142
TI  - Con: Sentinel lymph node biopsy for DCIS. The breast surgeon is not a barber.

PMID- 17009143
TI  - Liver transplantation: the preferred treatment for early hepatocellular carcinoma
      in the setting of cirrhosis?

PMID- 17009144
TI  - eRFA: excision followed by RFA-a new technique to improve local control in breast
      cancer.
AB  - INTRODUCTION: Excision followed by RFA (eRFA) may allow improved cosmesis while
      ensuring negative margins in patients with breast cancer. This technique utilizes
      heat to create an additional tumor-free zone around the lumpectomy cavity. We
      hypothesized that eRFA will decrease the need for re-excision of inadequate
      margins. METHODS: Between July 2002 and January 2005, we conducted a multiphase
      trial of RFA of prophylactic mastectomy specimens and of women desiring
      lumpectomy. In both models, a lumpectomy was performed, the RFA probe was
      deployed 1 cm circumferentially into the walls of the lumpectomy cavity and
      maintained at 100 degrees C for 15 min. Whole mount slides were used to measure
      the zone of ablation for ex vivo specimens. Hematoxylin and eosin staining of in
      vivo lumpectomy margins < 3 mm was considered inadequate. RESULTS: Nineteen
      prophylactic mastectomy ablations revealed a consistent perimeter of ablation.
      Forty-one patients (mean age 63 +/- 14 years) had an average tumor size of 1.6 +/
      1.5 cm underwent in vivo eRFA, and 25% had inadequate margins: one focally
      positive, one < 2 mm, eight < 1 mm and one grossly positive. Only the grossly
      positive margin was re-excised. Overall complication rate of in vivo ablations
      was 7.5%. Twenty-four of 41 patients did not have post-eRFA XRT. No in-site local
      recurrences have occurred during a median follow-up of 24 months (12-45 months).
      Two patients have occurred elsewhere. CONCLUSIONS: The ex vivo ablation model
      reliably created a 5-10 mm perimeter of ablation. In vivo, this zone reduced the
      need for re-excision for inadequate margins by 91% (10/11). Short-term follow-up
      suggests that eRFA could reduce re-excision surgery and local recurrence.

PMID- 17009145
TI  - Clinical implications of combined portal vein resection as a palliative procedure
      in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma.
AB  - BACKGROUND: The clinical implications of combined portal vein resections are
      controversial. METHODS: One-hundred and forty-nine consecutive patients underwent
      macroscopically curative pancreatectomies for pancreatic head carcinoma between
      January 1, 1996 and December 31, 2004. Portal vein resection was performed in 86
      patients (58%). Data on surgical mortality, morbidity, perioperative outcome,
      pathological factors, initial recurrence site, and survival were retrospectively
      compared between the patients with and without portal vein resection. RESULTS:
      The incidence of postoperative pancreatic fistula was lower among patients who
      underwent portal vein resection. The median survival period was 14 months for the
      portal vein resection group and 35 months for the non-portal vein resection
      group, respectively. Combined portal vein resection was a significant predictor
      of poor survival using a multivariate analysis. Portal vein resection was
      strongly associated with larger tumor size, the degree of retropancreatic tissue
      invasion, the presence of extrapancreatic nerve plexus invasion, lymph node
      metastases, and positive cancer infiltration at the surgical margins.
      CONCLUSIONS: Portal vein resection at the time of pancreaticoduodenectomy can be
      safely performed. However, most of patients requiring portal vein resection do
      not achieve a potentially curative resection or a favorable survival term. As a
      result, the aggressive application and the strict selection of portal vein
      resection might reduce the incidence of positive surgical margins, enabling long
      term survival in patients who do not require portal vein resection.

PMID- 17009146
TI  - Prognostic significance of postoperative morbidities in patients with advanced
      epithelial ovarian cancer treated with neoadjuvant chemotherapy and delayed
      primary surgical debulking.
AB  - BACKGROUND: To examine the prognostic significance of postoperative morbidities
      in patients with ovarian cancer treated with neoadjuvant chemotherapy and
      interval surgical debulking. METHODS: Retrospective chart reviews of all patients
      treated with neoadjuvant chemotherapy and interval debulking were performed from
      1999 to 2002. Descriptive statistics were used to summarize the distributions of
      important clinical variables. Logistic regression was used to identify
      statistically significant predictors of postoperative morbidities. Cox regression
      was used to model time to first clinical progression. Survivals were estimated by
      the Kaplan-Meier method and compared with the log rank test. P < .05 was
      considered to be statistically significant. RESULTS: Fifty-eight patients were
      treated with neoadjuvant platinum-taxane combination chemotherapy. Major surgical
      complications were observed in four patients (6.8%). There were no perioperative
      deaths. The presence of concurrent medical comorbidities was associated with the
      development of significant postoperative morbidities (P = .038). Cox regression
      showed any macroscopic residual disease (P = .04) and the presence of significant
      postoperative morbidities (odds ratio, 4.7, 95% confidence interval, 1.8-12.7, P
      = .002) to be predictive of a shorter progression-free interval. CONCLUSIONS:
      Neoadjuvant chemotherapy followed by interval surgical debulking carried a low
      risk for postoperative morbidity. The adverse influence of marked postoperative
      morbidity on progression-free survival needs further study.

PMID- 17009147
TI  - The prognostic effect of micrometastases in previously staged lymph node negative
      (N0) colorectal carcinoma: a meta-analysis.
AB  - BACKGROUND: The prognostic relevance of lymphatic micrometastases in colorectal
      carcinoma is unclear. To determine the prognostic significance of micrometastases
      in colorectal cancer, a meta-analysis was performed on all studies, which
      reported 3-year disease-free survival (DFS) and overall survival (OS). METHODS:
      Published studies selected for meta-analysis contained sufficient data from which
      to extrapolate estimates of 3-year DFS and/or OS. From 1991-2003, 25 studies re
      examined N0 lymph nodes by serial sectioning and immunohistochemical (IHC)
      staining or reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Eight
      studies (566 patients) with IHC detected micrometastases and three (173 patients)
      with RT-PCR micrometastases were used to determine DFS and OS. Weighted estimates
      of 3-year survival were combined across studies within each group, and the
      combined survival estimates were compared across groups using a binomial test.
      RESULTS: Micrometastases were identified in all IHC studies; upstaging, including
      N1, N1mi and N0(i+), was achieved in 32% (179/566 patients). All RT-PCR studies
      identified micrometastases; upstaging to N0(mol+) was achieved in 37% (64/173
      patients). There was a statistically significant difference in 3-year OS between
      RT-PCR positive N0(mol+) patients (77.8%) and those for whom micrometastases were
      not detected (96.6%) (P < .001). CONCLUSION: The prognostic value of
      micrometastases detected retrospectively by RT-PCR is significant in AJCC stage
      II colorectal patients. Studies utilizing RT-PCR performed a more complete nodal
      analysis when compared to studies using IHC techniques. RT-PCR may also be more
      specific for the detection of clinically relevant micrometastases compared to IHC
      detected cytokeratins. Prospective studies are needed to evaluate the potential
      benefit of systemic chemotherapy in patients with molecular metastases.

PMID- 17009148
TI  - Retroperitoneal and lateral pelvic lymphadenectomy mapped by lymphoscintigraphy
      and blue dye for rectal adenocarcinoma staging: preliminary results.
AB  - BACKGROUND: Total mesorectal excision (TME) is the standard surgical choice for
      rectal adenocarcinoma. Better prognostic results, achieved with a retroperitoneal
      and lateral pelvic lymphadenectomy (RLPL), have questioned that TME might not be
      satisfactory for adequate patient staging, affecting therapeutic definitions. The
      aims of the ongoing study are to define the accuracy of dye and probe search in
      the detection of metastatic retroperitoneal and lateral pelvic nodes (RLPN)
      resected with RLPL, and to evaluate the metastasis frequency in these nodes and
      its eventual upstaging impact. METHODS: Thirty rectal adenocarcinoma patients
      were submitted to RLPL, with RLPN mapping using technetium (Tc 99 m) and patent
      blue, having nodes examined histopathologically and immunohistochemically.
      RESULTS: Eight hundred and two nodes were analyzed, mean of 26.7 per patient;
      RLPL was responsible for 41% (330) of the examined nodes, mean of 11 per patient.
      Metastatic RLPN have occurred in 20% of the patients; the RLPN were metastatic in
      only 6.7% of the patients; RLPL upstaged 13.3%. For identification of metastatic
      RLPN with technetium, sensitivity was 33%, specificity 79%, positive predictor
      value (PPV) 29%, negative predictor value (NPV) 83% and false negative (FN) rate
      67%. For patent blue and technetium metastatic RLPN identification, sensitivity
      was 17%, specificity 92%, PPV 33%, NPV 82% and FN 83%. CONCLUSIONS: Preliminary
      results have pointed out technetium and blue dye low accuracy to identify
      metastatic RLPN; no metastatic RLPN were reported in the patients submitted to
      preoperative chemoradiation and important upstaging with RLPL. Considering no
      increase in morbi-mortality rates with RLPL, definitive conclusions will be
      obtained as the study carries on.

PMID- 17009149
TI  - Which gene is a dominant predictor of response during FOLFOX chemotherapy for the
      treatment of metastatic colorectal cancer, the MTHFR or XRCC1 gene?
AB  - BACKGROUND: Combination chemotherapy using oxaliplatin, 5-fluorouracil and
      folinic acid (FOLFOX) is known to be effective in the treatment of metastatic
      colon cancer. Genes regulating the actions of 5-fluorouracil and oxaliplatin have
      been identified, but precisely which gene is dominant has not yet been
      determined. The aim of the investigation reported here was to identify which gene
      polymorphism is a dominant factor in FOLFOX chemotherapy-the
      methylenetetrahydrofolate reductase (MTHFR) gene for 5-fluorouracil or the X-ray
      cross-complementing1 (XRCC1) gene for oxaliplatin. METHODS: Paraffin-embedded
      tissues from 54 patients with unresectable metastases from colorectal cancer who
      had undergone chemotherapy with the FOLFOX regimen were analyzed for MTHFR
      polymorphisms in the MTHFR gene (677C-->T, Ala-->Val mutation) and XRCC1 gene
      (Arg-->Gln substitution in exon 10). Response rates and survivals were compared
      by types of polymorphism. RESULTS: Analyses of the patterns of MTHFR polymorphism
      revealed that 29.6% of the patients showed no mutation, 51.6% showed heterozygous
      mutations, and 11.8% showed homozygous mutations. Analyses of the XRCC1
      polymorphism revealed that 60.8% of the patients showed no mutation, 31.4% showed
      heterozygous mutations, and 7.8% showed homozygous mutations. After four cycles
      of chemotherapy, 3.7% showed a complete response, 57.4% showed a partial response
      (PD) or stable disease, and 38.9% showed PD. The MTHFR polymorphism was not
      significant in predicting response and 30-month-survival (P > .1), whereas the
      XRCC1 polymorphism was a significant prognostic factor for both response (P =
      .038) and survival (P = .011). CONCLUSIONS: We found a higher rate of mutations
      in the MTHFR gene than in the XRCC1 gene in Korean colorectal cancer patients.
      Response to FOLFOX was better in the patient group with mutations for MTHFR and
      worse in the patient group with mutations for XRCC1. However, only the XRCC1
      polymorphism was a significant prognostic factor for the response to FOLFOX
      chemotherapy and short-term survival.

PMID- 17009150
TI  - Upstaging and improved survival of early breast cancer patients after
      implementation of sentinel node biopsy for axillary staging.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) has become a standard for axillary
      staging for early breast cancer patients. Prior studies suggest that SLNB may be
      more sensitive for the identification of lymph node disease than axillary lymph
      node dissection (ALND). We hypothesized that SLNB use increases the incidence of
      node-positivity in early breast cancer patients compared to ALND. Furthermore,
      survival improves due to more accurate staging (stage migration). METHODS:
      Registry data from an NCI-designated cancer center was reviewed for breast cancer
      patients with T1 and T2 tumors for two 5-year periods: before (1993-1997) and
      after (2000-2004) SLNB implementation (1998). TNM staging was updated to conform
      to American Joint Committee on Cancer (AJCC) 2003 guidelines. RESULTS: There were
      no differences in tumor size or stage groupings between the two time periods (n =
      316 and 577). There was a non-significant increase in the proportion of patients
      with lymph node involvement (32 vs. 27%; P = .16) after SLNB implementation;
      though a trend of increased incidence of single-node positive patients was
      observed (13 vs. 8%; P = .07). This was significant in patients with T1A/T1B
      tumors (10 vs. 3%; P = .04), though not seen in T1C or T2 tumors. Stage II
      survival improved in the later time period (P = .02). CONCLUSIONS: The increase
      in single-node positivity after SLNB implementation supports the theory that SLNB
      is more sensitive than ALND. Improvements in survival are likely due to the stage
      migration of patients who would have been node-negative by ALND (but were found
      to be node-positive by SLNB) in addition to improvements in adjuvant therapy.

PMID- 17009151
TI  - Ultrasonography and fine-needle aspiration cytology in the preoperative
      evaluation of melanoma patients eligible for sentinel node biopsy.
AB  - BACKGROUND: Ultrasonography with fine-needle aspiration cytology (FNAC) has
      proven to be a valuable diagnostic tool in the preoperative workup of patients
      with breast cancer or penile cancer eligible for sentinel lymph node biopsy. The
      aim of this study was to evaluate the use of this technique in the initial
      assessment of patients with primary cutaneous melanoma. METHODS: A total of 107
      patients with cutaneous melanoma eligible for sentinel node biopsy with
      clinically negative nodes were studied prospectively. Patients underwent
      ultrasonography of potentially involved basins and FNAC in case of a suspicious
      lymph node. The sentinel node procedure was omitted in patients with tumour
      positive lymph nodes in lieu of lymph node dissection. RESULTS: Ultrasonography
      with FNAC correctly identified disease preoperatively in two of the 107 patients
      (2%). Thirteen of the 22 patients (59%) with a suspicious node on
      ultrasonographic imaging but a tumour-negative fine-needle aspirate were shown to
      have involved nodes. Of the 85 patients with ultrasonographically normal nodes,
      25 (29%) were shown to have metastases. Of the total of 43 involved basins, 16
      contained metastases > 2 mm and 25 < or = 2 mm. CONCLUSIONS: In our hands, the
      sensitivity and specificity of preoperative ultrasonography to detect lymph node
      involvement in patients with melanoma are 34% and 87%, respectively. In
      combination with FNAC, this is 4.7% and 100%, respectively. This yield is
      insufficient for this technique to be used as a routine diagnostic tool in the
      selection of patients eligible for sentinel node biopsy.

PMID- 17009152
TI  - Hepatic resection for colorectal metastasis: impact of tumour size.
AB  - BACKGROUND: Many colorectal liver metastasis patients are denied surgical
      resection on the basis of tumour size. The aim of this study was to explore the
      impact of metastasis size on modern liver resection. METHODS: Using a
      prospectively collected database, this was a retrospective analysis of 484
      consecutive patients who underwent liver resection for colorectal liver
      metastases between 1993 and 2003. The cohort was divided into two groups: smaller
      metastases (< 8 cm) and larger metastases (> or = 8 cm). Those with larger
      metastases were then further stratified into big metastases (8-12 cm) and giant
      metastases (> 12 cm). Demographic, pathological, surgical technique and outcome
      data were compared between the groups. RESULTS: There were 88 (18%) patients with
      metastases measuring 8 cm or larger. There was an association between higher
      carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 levels and larger
      metastases. The actuarial 5-year survival for patients with larger metastases was
      38% compared with 42% for smaller metastases (not statistically significant).
      Patients with giant metastases had poorer overall and disease-free survival (both
      nonsignificant) compared with those with big metastases: 29% and 28% at 5 years,
      respectively. CONCLUSION: Patients with colorectal liver metastasis greater than
      8 cm and up to 12 cm in size should not be treated differently from those with
      smaller lesions.

PMID- 17009153
TI  - Percutaneous radiofrequency ablation of pulmonary metastases from colorectal
      carcinoma: prognostic determinants for survival.
AB  - BACKGROUND: Preliminary results have shown that percutaneous radiofrequency
      ablation (RFA) may play a useful role in patients with inoperable lung tumors.
      This series evaluated the prognostic features for survival in nonsurgical
      candidates who underwent percutaneous RFA of pulmonary metastases from colorectal
      carcinoma. METHODS: Fifty-five patients not suitable for surgery underwent
      percutaneous RFA for colorectal pulmonary metastases. All clinical and treatment
      related data were collected prospectively. The primary end point of the study was
      overall survival, defined from the time of RFA intervention. Univariate and
      multivariate analyses were performed to identify statistically significant
      prognostic parameters for overall survival. RESULTS: The overall median survival
      was 33 months (range, 4-40 months), with actuarial 1-, 2-, and 3-year survival of
      85%, 64%, and 46%, respectively. Univariate analysis demonstrated that largest
      size of lung metastasis (P < .001), location of lung metastases (P = .032), and
      repeat percutaneous RFA for pulmonary recurrence (P = .024) were statistically
      significant for overall survival. Multivariate analysis demonstrated that largest
      size of lung metastasis >3 cm was independently associated with a reduced overall
      survival (P = .003). CONCLUSIONS: Percutaneous lung RFA may play a useful role in
      nonsurgical candidates with colorectal pulmonary metastases. However, the
      survival benefit of this interventional procedure for patients with a pulmonary
      metastasis >3 cm was limited.

PMID- 17009154
TI  - Surgical management of pulmonary metastases from colorectal cancer in 153
      patients.
AB  - BACKGROUND: Surgery has become a recognized therapeutic means in selected
      patients with pulmonary metastases from colorectal origin. We reviewed our
      experience in the surgical treatment of 153 patients with pulmonary colorectal
      metastases and investigated factors affecting survival. METHODS: A retrospective
      analysis of the records of all patients (n = 153) with pulmonary metastases from
      colorectal cancer who underwent thoracotomy between 1978 and 2003 at a single
      surgical center was performed. RESULTS: One hundred fifty-three patients with
      pulmonary metastases from colon (n = 61) or rectal (n = 92) cancer underwent 180
      thoracotomies. The 2- and 5-year probabilities of survival after the first
      thoracotomy were 64% and 37%, respectively. Sex, age, site, International Union
      Against Cancer stage of the primary tumor, prethoracotomy carcinoembryonic
      antigen level, size of metastases, and previous resection of hepatic metastases
      were not found to be statistically significant prognostic factors. Number of
      metastases (solitary vs. multiple), mode of operation (wedge vs. anatomical
      resection), disease-free interval (DFI; > 36 months), negative hilar or
      mediastinal lymph node status, resection margin > 10 mm, and administration of
      intraoperative blood substitution were predictors of a longer survival duration
      by univariate analysis, but only number of metastases (P = .019), mode of
      operation (P = .004), DFI (P = .027), and intraoperative blood substitution (P =
      .002) were identified as independent prognostic factors by multivariate analysis.
      CONCLUSIONS: Pulmonary resection for metastases from colorectal cancer is safe
      and results in long-term survival in selected patients. Single metastases,
      anatomical resection, intraoperative blood substitution, and DFI > 36 months seem
      to be the most reliable predictors of survival.

PMID- 17009155
TI  - Patient satisfaction and aesthetic results after pedicled transverse rectus
      abdominis muscle flap for breast reconstruction.
AB  - BACKGROUND: The transverse rectus abdominis muscle (TRAM) flap is one of the most
      widely used procedures for breast reconstruction. Our aim was to evaluate the
      patient satisfaction and aesthetic results after pedicled TRAM flap. METHODS: One
      hundred thirty-three pedicled TRAM procedures were performed between 1993 and
      2000. A questionnaire was filled out by 101 patients, and they represented the
      study group. We investigated variables of general background, those related to
      the operation, and those connected with satisfaction. RESULTS: A total of 75% of
      women were satisfied with the operation, 73% declared high satisfaction, and only
      12% were dissatisfied with the results. A total of 86% were highly satisfied with
      their appearance in clothes, but only 48% were satisfied with their nude
      appearance. The lowest grade was given to breast sensation. A total of 82% noted
      high satisfaction of the spouse, compared with only 7% who stated a lack of
      satisfaction. Ninety percent claimed that there was no change in sexual
      attraction, 81% stated there was no change in sexual intercourse, and 79% noted
      no change in spousal attitude. Younger women reported better symmetry of breasts
      and a better sexual relationship with the spouse after the procedure. Women who
      did not undergo radiotherapy were more satisfied with all the aesthetic factors.
      CONCLUSIONS: Satisfaction is affected by many factors; both objective surgical
      factors and mental and psychological parameters vary among women. From this point
      of view, the pedicled TRAM flap can be considered a good option for women
      desiring breast reconstruction. Those who had immediate breast reconstruction
      were more satisfied with all measures.

PMID- 17009156
TI  - Ultrasound-guided fine-needle aspiration of clinically negative lymph nodes
      versus sentinel node mapping in patients at high risk for axillary metastasis.
AB  - BACKGROUND: Sonographically directed fine-needle aspiration is a less invasive
      and less costly alternative to sentinel node (SN) mapping in breast cancer
      patients at high risk for metastatic disease but with clinically negative
      axillae. METHODS: Radiographic, cytological, and histological diagnostic data on
      breast primary tumors from 114 consecutive SN candidates were prospectively
      assessed for clinicopathologic variables associated with an increased incidence
      of axillary metastases. Patients in whom these variables were identified
      underwent sonographic examination of their axillae followed by fine-needle
      aspiration when abnormal nodes were detected. SN mapping was performed in
      patients with normal axillary sonogram results or negative cytological results.
      Patients with positive cytological results proceeded to complete axillary
      dissection. Final axillary histological outcomes from patients not meeting the
      high-risk criteria were recorded. Additionally, a cost analysis was performed in
      which the costs of ultrasonography and ultrasound-guided fine-needle aspiration
      of the axilla were compared with those of SN mapping. RESULTS: According to our
      selection criteria, a third of the patients with clinically negative axillae (37
      of 114; 32%) were considered at high risk for axillary metastases. Fifty-nine
      percent of these patients (22 of 37) had metastatic disease on final histological
      analysis. Forty percent (15 of 37) of high-risk patients were spared SN mapping,
      with a reduction in health care costs of 20% in this patient population. Eighty
      seven percent of patients not meeting high-risk criteria were SN negative.
      CONCLUSIONS: This study suggests that in patients at increased risk for axillary
      metastases, the use of sonographic evaluation of the axilla in combination with
      fine-needle aspiration is not only clinically justified, but also cost-effective.

PMID- 17009157
TI  - Hepatectomy for peripheral cholangiocarcinoma in elderly patients.
AB  - BACKGROUND: Peripheral cholangiocarcinoma (CCC) is less common than
      hepatocellular carcinoma. Little is known about CCC patients older than 70 years
      who have undergone hepatectomy. METHODS: Between 1977 and 2004, the clinical
      features of 33 elderly CCC patients (>70 years old) undergoing hepatectomy were
      reviewed, and 185 CCC patients younger than 70 years (younger CCC) were used for
      comparison. RESULTS: A total of 218 CCC patients undergoing hepatectomy were
      investigated with ages ranging from 28 to 93 years (median, 59.0 years). The
      elderly and younger CCC groups had a similar sex ratio and a similar positive
      rate of carcinoembryonic antigen (CEA) and CA19-9. A similar rate of
      hepatolithiasis, mucobilia, papillary pattern, stage distribution, curative
      hepatectomy, surgical morbidity, and mortality for CCC were also observed between
      the two groups. During a follow-up duration ranging from 1.1 to 145.0 months
      (median, 11.7 months), elderly CCC and younger CCC patients had similar prognoses
      after hepatectomy (P = .827). Elderly CCC patients with a low CEA level, an
      intraductal papillary growth pattern, curative hepatectomy, and postoperative
      chemotherapy tended to have favorable survival. However, elderly CCC patients
      with a low CEA level independently showed favorable survival. CONCLUSIONS:
      Hepatectomy is feasible for selected elderly CCC patients. Elderly CCC patients
      undergoing hepatectomy had clinicopathologic features and prognoses similar to
      those of patients younger than 70 years undergoing hepatectomy. Elderly CCC
      patients with a low CEA level, intraductal papillary growth pattern, curative
      hepatectomy, and postoperative chemotherapy tended to have favorable survival.
      However, elderly CCC patients with low CEA level independently showed favorable
      survival.

PMID- 17009158
TI  - Differences in sentinel lymph node pathology protocols lead to differences in
      surgical strategy in breast cancer patients.
AB  - BACKGROUND: Internationally, there is no consensus on the pathology protocol to
      be used to examine the sentinel lymph node (SN). At present, therefore, various
      hospitals use different SN pathology protocols of which the effect has not been
      fully elucidated. We hypothesized that differences between hospitals in SN
      pathology protocols affect subsequent surgical treatment strategies. METHODS:
      Patients from four hospitals (A-D) were prospectively registered when they
      underwent an SN biopsy. In hospitals A, B, and C, three levels of the SN were
      examined pathologically, whereas in hospital D, at least seven additional levels
      were examined. In the absence of apparent metastases with hematoxylin and eosin
      examination, immunohistochemical examination was performed in all four hospitals.
      RESULTS: In total, 541 eligible patients were included. In hospital D, more
      patients were diagnosed with a positive SN (P < .001) as compared with hospitals
      A, B, and C, mainly because of increased detection of isolated tumor cells. This
      led to more completion axillary lymph node dissections in hospital D (66.3% of
      patients (P < .0001), compared with 29.0% in hospitals A, B, and C combined).
      Positive non-SNs were detected in 13.9% of patients in hospital D, compared with
      9.7% in hospitals A, B, and C (P = .70). That is, in 52.4% of patients in
      hospital D, a negative completion axillary lymph node dissection was performed,
      compared with 19.3% of patients in hospitals A, B, and C combined. CONCLUSIONS:
      Differences in SN pathology protocols between hospitals do have a substantial
      effect on SN findings and subsequent surgical treatment strategies. Whether
      ultrastaging and, thus, additional surgery can offer better survival remains to
      be determined.

PMID- 17009159
TI  - Analysis of loss of heterozygosity for tumor-suppressor genes can accurately
      classify and predict the clinical behavior of mucinous tumors arising from the
      appendix.
AB  - BACKGROUND: Pseudomyxoma peritonei is a rare heterogenous clinical syndrome with
      a variable clinical course. On the basis of the hypothesis that cumulative
      mutational damage can predict biological aggressiveness, we evaluated the utility
      of integrated histopathology and molecular analysis for patients with
      pseudomyxoma peritonei syndrome. METHODS: Tissue specimens from 23 mucinous
      appendiceal tumors were analyzed. DNA samples from multiple sites were analyzed
      for loss of heterozygosity by using a panel of 15 allelic loss microsatellite
      markers and K-ras-2 point mutational damage. The fractional mutational rate
      (FMR), determined as the number of mutated markers divided by the total number of
      informative markers, was calculated by using the six most informative markers and
      the K-ras-2 gene. Kappa statistics were calculated to test the association
      between FMR and the histopathologic classification. RESULTS: Our study included 6
      female and 17 male patients with a mean age of 53.6 years and a mean survival of
      43.9 months. We found an association between tumor loss of heterozygosity markers
      and histopathologic classification (P < .05). In addition, there was also an
      association between the FMR and pathological classification as well as between
      the FMR and survival (P < .05). An FMR less than .25 indicated low-grade disease,
      an FMR of .25 to .50 indicated intermediate grade, and an FMR greater than .5
      indicated a high-grade tumor. CONCLUSIONS: Mutational profiling of accumulated
      allelic loss and point mutational damage correlated strongly with histopathologic
      definitions of pseudomyxoma peritonei disease and helped to predict the prognosis
      of these patients. FMR, along with histopathology, offers a comprehensive
      classification of these rare tumors.

PMID- 17009160
TI  - REG I expression predicts long-term survival among locally advanced thoracic
      squamous cell esophageal cancer patients treated with neoadjuvant
      chemoradiotherapy followed by esophagectomy.
AB  - BACKGROUND: The prognosis for patients with locally advanced thoracic esophageal
      cancer is extremely unfavorable. We have been administering neoadjuvant
      chemoradiotherapy (CRT) followed by esophagectomy to these patients and studying
      whether REG I expression in untreated endoscopic biopsy specimens is predictive
      of patient responsiveness to CRT and/or survival after treatment. METHODS:
      Between 1992 and 2003, 47 patients with T4 (direct invasion of adjacent organs)
      thoracic esophageal cancers were administered neoadjuvant CRT followed by
      esophagectomy. REG I expression was assessed in untreated endoscopic biopsy
      specimens and correlated with clinical and histological responses and survival in
      37 patients who had also undergone curative surgery. RESULTS: Among the 37 cases
      that received CRT followed by surgery, the therapeutic response rate for
      neoadjuvant CRT was 68%, and a complete histological response in resected
      specimens from the primary lesion was achieved in 8 (22%) patients. These
      clinical and histological responses to neoadjuvant CRT did not significantly
      correlate with survival, however. By contrast, 9 patients were judged REG
      positive based on analysis of their untreated endoscopic biopsy specimens, and
      their cumulative survival rate was significantly higher than that of the 28 REG
      negative patients (P = 0.0073). Univariate analysis showed REG I expression to be
      a prognostic factor (P = 0.0386) that increased the risk of death 8.4-fold.
      CONCLUSIONS: Evaluation of REG I expression in untreated endoscopic biopsy
      specimens may provide a basis for new treatments of locally advanced thoracic
      squamous cell esophageal cancers.

PMID- 17009161
TI  - Nuclear translocation of beta-catenin protein but absence of beta-catenin and APC
      mutation in gastrointestinal carcinoid tumor.
AB  - BACKGROUND: Carcinoid tumors are a group of heterogeneous tumors with
      neuroendocrine differentiation and are mainly located in the gastrointestinal
      tract. A high frequency of cytoplasmic accumulation and/or nuclear translocation
      of beta-catenin with frequent mutations of exon 3 of beta-catenin gene in
      gastrointestinal carcinoid tumor has been previously described, but the role of
      Wnt/beta-catenin/APC pathway in the genesis of carcinoid tumor remains largely
      unknown. METHODS: To further characterize the role of Wnt/beta-catenin/APC
      pathway, we investigated 91 gastrointestinal carcinoid tumors and, for
      comparison, 26 extragastrointestinal carcinoid tumors by immunohistochemical
      detection of beta-catenin protein and direct sequencing of exon 3 of the beta
      catenin gene and exon 15 of the APC gene. RESULTS: Cytoplasmic accumulation
      and/or nuclear translocation of beta-catenin were found in 27 gastrointestinal
      carcinoid tumors (29.7%) but not in any extragastrointestinal carcinoid tumors.
      Interestingly, neither beta-catenin nor APC gene mutation was detected in all of
      the cases with nuclear expression of beta-catenin. CONCLUSIONS: Our results
      indicate that the role beta-catenin plays in the genesis of gastrointestinal and
      extragastrointestinal carcinoid tumors is different. Nuclear expression of beta
      catenin does not occur in extragastrointestinal carcinoid tumors, and mutation of
      exon 3 of beta-catenin gene and exon 15 of APC gene does not contribute to the
      activation of Wnt/beta-catenin/APC pathway in gastrointestinal carcinoid tumors.

PMID- 17009162
TI  - Bleeding, obstruction, and perforation in a series of patients with aggressive
      gastric lymphoma treated with primary chemotherapy.
AB  - BACKGROUND: The management of patients with gastric lymphoma has evolved, with a
      shift toward nonsurgical treatment. The rates of surgical complications in
      patients receiving chemotherapy have been insufficiently studied. The objective
      of this study was to assess the frequency of bleeding, perforation, and gastric
      outlet obstruction in patients who received chemotherapy as primary treatment for
      gastric diffuse large B cell lymphoma (DLBCL). METHODS: We reviewed files of all
      patients with gastric DLBCL who were diagnosed and treated primarily with
      chemotherapy in our hospital between 1990 and 2005. RESULTS: Eighteen (25%) of 73
      patients experienced surgical complications, of whom 6 (8%) underwent surgery.
      Eight patients (11%), six with active lymphoma, experienced gastric bleeding; one
      required gastrectomy. Eight patients (11%) developed gastric outlet obstruction,
      of whom three were treated conservatively, three required surgery, one stopped
      treatment, and one received further chemotherapy. Six of the eight patients had
      no evidence of active lymphoma at the time of obstruction. Two additional
      patients underwent gastrectomy due to resistant or relapsed disease. Gastric
      perforation was not observed. Median survival was 90 months for the entire
      series, 94 months for patients with gastric outlet obstruction, and 11.5 months
      for patients with gastric bleeding. CONCLUSIONS: Given the rate of surgical
      complications, especially gastric bleeding and gastric outlet obstruction, there
      is still an important role for the surgical consultant in the treatment of
      patients with gastric DLBCL receiving chemotherapy. Gastric perforation, although
      frequently cited as a complication, is in fact rarely observed.

PMID- 17009163
TI  - Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische
      Onkologie (AGO) DESKTOP OVAR trial.
AB  - BACKGROUND: The role of cytoreductive surgery in relapsed ovarian cancer is not
      clearly defined. Therefore, patient selection remains arbitrary and depends on
      the center's preference rather than on established selection criteria. The
      Descriptive Evaluation of preoperative Selection KriTeria for OPerability in
      recurrent OVARian cancer (DESKTOP OVAR) trial was undertaken to form a hypothesis
      for a panel of criteria for selecting patients who might benefit from surgery in
      relapsed ovarian cancer. METHODS: The DESKTOP trial was an exploratory study
      based on data from a retrospective analysis of hospital records. Twenty-five
      member institutions of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian
      Committee (AGO OC) and AGO-OVAR boards collected data on their patients with
      cytoreductive surgery for relapsed invasive epithelial ovarian cancer performed
      in 2000-2003. RESULTS: Two hundred and sixty-seven patients were included.
      Complete resection was associated with significantly longer survival compared
      with surgery leaving any postoperative residuals [median 45.2 vs. 19.7 months;
      hazard ratio (HR) 3.71; 95% confidence interval (CI) 2.27-6.05; P < .0001].
      Variables associated with complete resection were performance status (PS)
      [Eastern Cooperative Oncology Group (ECOG) 0 vs. > 0; P < .001], International
      Federation of Gynecology and Obstetrics (FIGO) stage at initial diagnosis (FIGO
      I/II vs. III/IV, P = .036), residual tumor after primary surgery (none vs.
      present, P <.001), and absence of ascites > 500 ml (P < .001). A combination of
      PS, early FIGO stage initially or no residual tumor after first surgery, and
      absence of ascites could predict complete resection in 79% of patients.
      CONCLUSIONS: Only complete resection was associated with prolonged survival in
      recurrent ovarian cancer. The identified criteria panel will be verified in a
      prospective trial (AGO-DESKTOP II) evaluating whether it will render a useful
      tool for selecting the right patients for cytoreductive surgery in recurrent
      ovarian cancer.

PMID- 17009164
TI  - A gene expression profile for vascular invasion can predict the recurrence after
      resection of hepatocellular carcinoma: a microarray approach.
AB  - BACKGROUND: Recurrence after hepatocellular carcinoma (HCC) resection is the
      major obstacle to improved survival. The presence of vascular invasion (VI) in
      pathology specimens is a well-known unfavorable prognostic factor for HCC
      recurrence. Though some VI-related genes have been reported, their association
      with recurrence-free survival is not known. We hypothesized that a gene
      expression profile for VI can predict the recurrence of HCC after liver
      resection. METHODS: Eighteen patients receiving complete HCC resection were
      included as a "training group". Genome-wide gene expression profile was obtained
      for each tumor using a microarray technique. Datasets were subjected to
      clustering analysis supervised by the presence or absence of VI to obtain 14
      discriminative genes. We then applied those genes to execute pattern recognition
      using the k-Nearest Neighbor (KNN) classification method, and the best model for
      this VI gene signature to predict recurrence-free survival in the training group
      was obtained. The resulting model was then tested in an independent "test group"
      of 35 patients. RESULTS: A 14-gene profile was extracted which could accurately
      separate ten patients with VI and eight patients without VI in the "training
      group". In the "test group", significant difference in disease-free survival was
      found between patients predicted to have and not to have recurrence (P = .02823).
      In patients with stage_I disease, this model can also predict outcomes (P =
      .000205). CONCLUSIONS: Using the 14-gene expression profile extracted from
      microarrays based on the presence of VI can effectively predict recurrence after
      HCC resection. This approach might facilitate "personalized medicine" for HCC
      patients after surgical resection.

PMID- 17009165
TI  - Maspin expression and its clinical significance in non-small cell lung cancer.
AB  - BACKGROUND: Maspin is a member of the serpin (serine protease inhibitor)
      superfamily, and its exact function in the development and progression of
      malignant tumors remains controversial, though some experimental studies have
      revealed potential tumor-suppressor activities. In addition, there have been only
      a few clinical studies on maspin expression in malignant tumors including non
      small cell lung cancer (NSCLC). The purpose of this study was to assess maspin
      expression and its clinical significance in NSCLC. METHODS: A total of 210
      consecutive patients with completely resected pathological (p-) stage I-IIIA
      NSCLC were retrospectively reviewed. Maspin expression along with intratumoral
      microvessel density, proliferative activity, and p53 status were evaluated
      immunohistochemically. The incidence of apoptotic cell death was also evaluated.
      RESULTS: The incidence of strong maspin expression was significantly higher in
      lung squamous cell carcinoma (56/76, 73.7%; P < .001) than in other histological
      types. The incidence of aberrant expression of p53 was significantly higher in
      maspin-strong than in maspin-weak tumors (56.2% and 35.8%, respectively; P =
      .005). There was no difference in prognosis according to maspin status for all
      patients. However, for squamous cell carcinoma patients, univariate analysis
      showed that enhanced maspin expression was a significant factor in predicting a
      favorable prognosis (5-year survival rates, 70.1% for maspin-strong tumors and
      41.5% for maspin-weak tumors; P = .014), which was confirmed in a multivariate
      analysis (hazard ratio = .475, 95% confidence interval .241-.936; P = .032).
      CONCLUSIONS: Enhanced maspin expression was a significant and independent factor
      in predicting a favorable prognosis in lung squamous cell carcinoma.

PMID- 17009166
TI  - Bioavailability of vitamins A and E from whole and vitamin-fortified milks in
      control subjects.
AB  - BACKGROUND: Dairy products fortified with vitamins and minerals represent a
      growing market that is of interest to those sectors of the population with
      unbalanced diets and increased needs. However, there is little information on the
      bioavailability of micronutrients in milk products at dietary intake levels. AIM
      OF THE STUDY: To evaluate the bioavailability of vitamins A and E in whole milk
      and fortified whole and skimmed milk in control subjects. METHODS: A single-dose
      bioavailability study was performed using three commercially available milks
      (unfortified whole milk and whole and skimmed milk fortified with vitamins A and
      E). Nineteen volunteers (10 women and 9 men) ingested 430 ml of each milk on
      different days. The contents of retinol and alpha-tocopherol provided in the
      milks and the retinyl esters and alpha-tocopherol in triglyceride-rich
      lipoprotein fractions (TRL) from plasma collected for 6.5 h postprandially were
      assayed using a quality-controlled HPLC method. The relative absorption of
      vitamins A and E from milks was calculated on the basis of area under the curve
      (AUC) versus time curve estimations, adjusted for plasma volume and expressed as
      percentage of the amount of nutrient provided. RESULTS: The total amounts of
      retinol and alpha-tocopherol provided ranged between 0.48 and 4.15 micromol and
      0.41 and 32.49 micromol, respectively. The AUC value of retinyl palmitate in TRL
      was higher for fortified whole milk than for the other two milks (unfortified
      whole and fortified skimmed milk). The percent relative absorption of vitamin A
      did not differ among the three types of milk. The AUC for alpha-tocopherol was no
      different after the ingestion of any of these milks. CONCLUSION: The mean
      percentage of retinol absorption was apparently similar for the three types of
      milk, regardless of the amount of fat ingested with each type of milk and the
      vitamin A provided.

PMID- 17009167
TI  - Transport, deglycosylation, and metabolism of trans-piceid by small intestinal
      epithelial cells.
AB  - BACKGROUND: Numerous epidemiological and animal studies have shown that
      consumption of red wine is related to reduced incidence of cardiovascular
      diseases and cancer. Trans-resveratrol (3, 5, 4'-trihydroxystilbene), a phenolic
      compound present in wine, has been reported to have a potential cancer
      chemopreventive activity. Moreover, it may exert a protective effect against
      atherogenesis through its antioxidant properties. Trans-piceid (3-ss glucoside of
      trans-resveratrol) is present to a greater extent than its aglycone in red wine,
      but hydrolysis of this glycosylated derivative can occur in small intestine and
      liver, which would enhance the amount of the biological active trans-resveratrol.
      AIMS: The present study aimed to investigate the rate of transepithelial
      transport of trans-piceid using human intestinal Caco-2 cell monolayers and
      metabolism of this compound during its absorption across the small intestine.
      METHODS: The transport of trans-piceid was evaluated in the human epithelial cell
      line Caco-2, which possesses enterocyte-like properties in vitro. For
      transepithelial experiments, confluent monolayers of Caco-2 cells were grown on
      Transwell inserts. For metabolic studies, we used both Caco-2 cells seeded on 6
      well plates and rat small intestine cell-free extracts. RESULTS: The time course
      of apical (AP) to basolateral (BL) transport of trans-piceid showed that the
      favorable apparent permeability coefficient (Papp) declined rapidly during the 6
      h of the experiment. This observation could be correlated with the appearance of
      metabolites. After incubation of Caco-2 cells with trans-piceid, trans
      resveratrol was detected on both AP and BL sides. By using protein extracts
      obtained from rat, we conclude that the Lactase Phlorizin Hydrolase (LPH) and
      Cytosolic-ss-Glucosidase (CBG) are involved in the hydrolysis of trans-piceid.
      Furthermore, we show that after deglycosylation, the resulting aglycone is
      metabolized in trans-resveratrol-3-O-ss-glucuronide and to a lesser extent in
      trans-resveratrol-4'-O-ss-glucuronide, and that UGT1A1 is mainly involved in this
      metabolism. CONCLUSIONS: This study demonstrates that the transepithelial
      transport of trans-piceid occurs at a high rate and that the compound is
      deglycosylated in trans-resveratrol. There are two possible pathways by which
      trans-piceid is hydrolyzed in the intestine. The first is a cleavage by the CBG,
      after passing the brush-border membrane by SGLT1. The second is deglycosylation
      on the luminal side of the epithelium by the membrane-bound enzyme LPH, followed
      by passive diffusion of the released aglycone, which is further metabolized
      inside the cells into two glucuronoconjugates.

PMID- 17009168
TI  - [The trochanteric flip osteotomy.].
AB  - GOAL OF SURGERY: Easy access to the posterior, superior and anterior joint
      capsule through an osteotomy which reduces the risk of complications and the
      incidence of non-union. INDICATIONS: Hip joint revision with or without
      intertrochanteric osteotomy, periarticular ossifications, difficult total hip
      procedures, exchange procedures. CONTRAINDICATIONS: Absolute: None Relative:
      Distal transfer of the trochanter. PREOPERATIVE WORK UP: Radiographs in 2 planes
      (anterior-posterior pelvis+"false profile" hip). POSITIONING AND ANAESTHESIA:
      Lateral decubitus. General anaesthesia. SURGICAL TECHNIQUE: In lateral decubitus
      the greater trochanter will be osteotomized from posterior leaving a 1 to 1.5 cm
      thick bony wafer uniting the insertion of the gluteus medius and minimus with the
      origin of the vastus lateralis. The trochanteric crest remains untouched. After
      refixation with nonresorbable sutures #3 the fragment is not subjected to a
      unidirectional tension by the abductors which could interfere with the
      consolidation. POSTOPERATIVE MANAGEMENT: Bed rest with lower limb in neutral
      position. Mobilization with 2 canes on the 2nd postoperative day. The timing of
      partial weight bearing depends on the type of surgery. Abductor exercises after 6
      weeks. POSSIBLE COMPLICATIONS: Bony wafer too thin or too thick. Inadequate
      refixation. Delayed consolidation. Cranial migration of the greater trochanter.
      RESULTS: Between 1991 and 1994 41 patients were operated. Diagnoses, see Table 1.
      Method of refixation: see Table 2. After 21+/-9 months 39 patients could be
      reexamined clinically, and radiological after 17+/-11 months: 38 osteotomies
      consolidated. Cranial migration varied between 0 and 8 mm. 25 patients were free
      of symptoms, 12 had slight and 2 moderate pain over the trochanter. Avulsion of
      wire cerclage: 2, foreign body irritation: 2 necessitating implant removal.

PMID- 17009170
TI  - [Not Available].

PMID- 17009169
TI  - [Total hip replacement in presence of acetabular dysplasia type II according to
      the AAOS classification.].
AB  - GOAL OF SURGERY: Incorporation of the acetabular cup in ideal position in
      patients with a primary dysplastic acetabulum. Two thirds of the surface of the
      cup must be covered by bone. INDICATIONS: Joint replacement in patients with
      acetabular dysplasia type II according to the AAOS classification.
      CONTRAINDICATIONS: Presence of acetabular dysplasia types I and III according to
      the AAOS classification. PREOPERATIVE WORK UP: Radiographic measurement of the
      acetabular depth and width using templates. POSITIONING AND ANAESTHESIA: Supine,
      affected side of pelvis slightly elevated. General or spinal anaesthesia. Special
      set of instruments mandatory. SURGICAL TECHNIQUE: Insertion of an acetabular cup
      through a lateral approach. Reaming of the acetabulum and filling of the defect
      under compression with a mixture of autogenous, morcellized bone from the
      resected femoral head and fibrin glue. Coverage of the transplanted bone with a
      pedicled capsular flap. POSTOPERATIVE MANAGEMENT: Phlebitis prophylaxis. Walking
      with 2 forearm crutches on the first postoperative day. Removal of stitches after
      10 days. Thereafter gradual increase of weight bearing (10 kg every second day,
      use a bathroom scale to check loading). Once full weight bearing and full muscle
      control have been reached, use of 1 crutch is allowed. Radiographic control after
      6 weeks, 3,6 and 12 months and yearly thereafter. POSSIBLE COMPLICATIONS:
      Perforation of the bony acetabulum. Fracture of the anterior or posterior
      acetabular rim. Thrombophlebitis, lung embolism, infection and/or periarticular
      ossification. RESULTS: Between 1986 and 1994 the technique has been used in 140
      hips with congenital dysplasia (type II according to the AAOS classification) and
      secondary osteoarthritis. 132 hips were regularly assessed and the mean of follow
      up was 6.2 years (1 to 9 years). The mean age of the mostly female patients was
      48 years (28 to 62 years). Only porous surfaced metallic cups without cement were
      used. The following complications were observed: thrombophlebitis 1, superficial
      infection 1, transient paresis of the fibular nerve 1 and transient irritation of
      the femoral nerve 3 (see Table 2). Additional complications such as thigh pain,
      periarticular ossification and resorption of the bone graft are listed in Table
      3. Complete bony incorporation of the bone grafts was seen in 122 hips.
      Resorption up to 8 mm occurred in the remaining 10 hips.

PMID- 17009172
TI  - [A trochanteric retractor.].
AB  - Presentation of a special trochanteric retractor for insertion around the greater
      trochanter replacing the common Hohmann retractor. Its blade is bent concavely
      and therefore adapts easily to the bony contour. Its surface is roughened. The
      spike is bent upward by thus providing a reliable hold between the insertions of
      the short external rotators. This diminishes the danger of an injury to the
      sciatic nerve. This new instrument has been successfully used for 6 years.

PMID- 17009171
TI  - [Anatomical comment: Hohmann retractor. A source of danger to the sciatic
      nerve.].
AB  - In referring to the article by Stuhmer the authors describe the topographic
      relationship between the sciatic nerve and an inserted normal Hohmann retractor
      or a specially designed retractor by Stuhmer. By simulating the surgical
      circumstances the following observations are made:In lateral position and with
      external rotation of the hip the sciatic nerve is found directly posterior to the
      major trochanter. When inserting the Hohmann retractor its point slips between
      the trochanter and the sciatic nerve. The nerve lies directly on the retractor or
      can be injured by inserting it. Contrary to this the Stuhmer retractor avoids
      pressure on or skewing of the nerve.

PMID- 17009173
TI  - [Reconstruction of acute anterior cruciate ligament rupture by suture and
      semitendinosus tendon augmentation.].
AB  - GOAL OF SURGERY: Restoration of normal knee function. INDICATIONS: Acute avulsion
      of the anterior cruciate ligament (ACL) from its femoral origin.
      CONTRAINDICATIONS: Mid substance and remote tears. POSITIONING AND ANAESTHESIA:
      Supine. Knee flexed, hip bent to 30 degrees . General or regional anaesthesia.
      SURGICAL TECHNIQUE: Step 1: Arthroscopy to confirm site of rupture, meniscus
      repair if necessary. Step 2: Mobilisation of semitendinosus tendon, left attached
      distally. Step 3: Mini-arthrotomy, securing of ACL stump with atraumatic suture.
      Step 4: Transfer of ST-tendon through 5 mm drill holes through tibial head and
      lateral femoral condyle. Step 5: Fixation of tendon and ACL-sutures with staple
      at the exit of the femoral drill hole. POSTOPERATIVE MANAGEMENT: Knee orthosis
      for 6 weeks, CPM, physiotherapy. ROM day 0-2: 0-10-10 degrees ; day 3-11: 0-0-60
      degrees , day 12-42: 0-0-90 degrees . Increase of weight bearing 10 kg/week from
      operation date. Bicycling and running permitted 3 months post-op. Full sport
      activity after muscle power has reached that of opposite side. LMW heparin until
      full weight bearing. POSSIBLE COMPLICATIONS: Thrombosis. Embolism. Infection.
      Failure of reconstruction. Osteoarthritis. RESULTS: During 1 year, 116 patients
      were operated. Follow-up after 42 to 57 months (average 52 months) included 95
      patients (82%). Of these, 76 underwent full examination (average age 33 1/2
      years, 20-49 years), 11 answered a questionnaire, 8 had suffered re-injury.
      Average Lysholm score was 92 points (+/-13). Tegner activity scale amounted to
      7.2 points pre-injury, 7.1 points at follow-up. Anterior translation (KT 1000
      arthrometer testing at 89 N) was identical to opposite side in 25 patients, less
      than 2 mm in 14, up to 4 mm in 19, up to 6 mm in 15, more that 6 mm in 3
      patients. Pivot shift was negative or trace 73 times, and positive in 3 patients.
      ROM was full in 54 patients, 17 times the flexion was limited up to 10 degrees .
      Ten times extension lag was less than 5 degrees , and twice between 5 and 10
      degrees .

PMID- 17009174
TI  - [Not Available].

PMID- 17009175
TI  - Conservative amputation of the neuropathic foot- The Pirogoff procedure.
AB  - INDICATIONS: Lesions limited to the forefoot when reconstruction of the forefoot
      is impossible. In situations where due to the unavailability of protheses a
      forefoot amputation has to be done. CONTRAINDICATIONS: Absolute: Badly scarred or
      destroyed calcaneum and/or heel pad. Osteomyelitis of lower tibia or calcaneum.
      Malignancy of the heel area. Relative: Inadequate circulation of the heel area.
      Uncontrolled diabetes mellitus. SURGICAL TECHNIQUE: Forefoot amputation with
      arthrodesis between tibia and os calcis. Specially applicable in patients with
      neuropathy because this simple procedure leaves a stable stump. Prosthetic
      fitting not mandatory. Negligible shortening of limb. POSTOPERATIVE MANAGEMENT:
      Bed rest, elevation of limb, and protective splinting for 3 postoperative days.
      Non weight bearing on crutches for the next 2 weeks, then well fitted contact
      cast with Bohler iron for walking. Application of prosthesis not before bony
      consolidation. POSSIBLE COMPLICATIONS: Infections. Treat very intensively.
      RESULTS: Fifty modified Pirogoff procedures were done over 30 years, mostly for
      leprosy or malignancy. Long-term follow-up available of 16 patients who suffered
      from leprosy (see Figure 11).

PMID- 17009176
TI  - [Closed reduction and percutaneous pinning for acute type III extension-
      Supracondylar fracture of distal humerus in children.].
AB  - GOAL OF SURGERY: Closed reduction of acute type III (according to Gartland)
      supracondylar extension fractures of the distal humerus and unicondylar pin
      fixation. INDICATIONS: Type III and unstable type II supracondylar fractures.
      CONTRAINDICATIONS: Swelling of the elbow. Compartment syndrome. PREOPERATIVE WORK
      UP: Radiographs of both elbows in the anterior-posterior and lateral projections.
      POSITIONING AND ANAESTHESIA: Supine with arm on arm board. General anaesthesia.
      SURGICAL TECHNIQUE: Closed reduction through manipulation under fluoroscopic
      control. Fixation with 2 Kirschner wires introduced percutaneously through the
      lateral condyle. Long arm cast for 4 to 5 weeks. POSTOPERATIVE MANAGEMENT:
      Radiographs on the first postoperative day, 1 week later and at time of cast and
      pin removal 4 to 5 weeks postoperatively. At that time active mobilisation of the
      elbow is started. Follow-up for 1 to 2 years is recommended. POSSIBLE
      COMPLICATIONS: Damage of ossific nucleus of physis. Damage to neurovascular
      structures. Wire migration. Pin tract infection. RESULTS: Out of 82 children
      (mean age 6.5 years) 73 had a follow-up of more than 6 months. 80.8% had good or
      excellent results. 15.1% had a decrease of the carrying angle of more than 10
      degrees (4.1% more than 20 degrees ). There were 2 pin tract infections and 1
      iatrogenic transient ulnar palsy.

PMID- 17009177
TI  - Modified Burton and Pellegrini procedure for trapezium excision, ligament
      reconstruction and interposition arthroplasty of the tendon of flexor Carpi
      radialis.
AB  - GOAL OF SURGERY: Relieve of pain and increased stability at the base of 1st
      metacarpal. INDICATIONS: Painful degenerative and inflammatory arthritis in
      trapeziometacarpal joint (TMCJ). CONTRAINDICATIONS: Patients not willing to
      undergo lengthy intensive postoperative rehabilitation. Rheumatoid arthritis
      (relative). POSITIONING AND ANAESTHESIA: Supine. Hand table. General or regional
      anaesthesia. SURGICAL TECHNIQUE: Modification of the Burton-Pelligrini operation
      by using half of the flexor carpi radialis for interposition between base of 1st
      metacarpal and scaphoid. Stabilization with a Kirschner wire. In the presence of
      scaphotrapezoid arthritis an arthrodesis of this joint is performed for better
      pain control. POSTOPERATIVE MANAGEMENT: Immobilization in a below elbow cast for
      6 weeks. Then active physiotherapy, night splint for another 6 weeks. POSSIBLE
      COMPLICATIONS: Fracture while drilling the base of the 1st metacarpus, migration
      of Kirschner wires, injury to the radial artery and cutaneous nerves. RESULTS:
      Out of 15 patients 12 (14 thumbs) were followed for at least 6 months. In 11
      patients the shape of the hand was normal and 10 patients were satisfied with the
      result of the operation. Complications included: twice postoperative migration of
      Kirschner wires, and once intraoperative tearing of the tendon which had to be
      sutured.

PMID- 17009178
TI  - Comment : to the publication of N. Maffulli et al.: Modified Burton and
      Pellegrini Procedure for Trapezium Excision, Ligament Reconstruction, and
      Interposition Arthroplasty of the Tendon of Flexor Carpi Radialis.

PMID- 17009179
TI  - Response : to the commentary of W. Epping to the publication: Modified Burton and
      Pellegrini Procedure for Trapezium Excision, Ligament Reconstruction, and
      Interposition Arthroplasty of the Tendon of Flexor Carpi Radialis.

PMID- 17009181
TI  - Research in family medicine.

PMID- 17009180
TI  - More on the research enterprise.

PMID- 17009182
TI  - Advising for international health electives.

PMID- 17009183
TI  - Getting more involved in STFM.

PMID- 17009184
TI  - Accompanying physicians in their family practice: a primary care model for
      medical students' learning in Brazil.

PMID- 17009186
TI  - Finding meaning in suffering and healing.

PMID- 17009187
TI  - Entry of US medical school graduates into family medicine residencies: 2005-2006
      and 3-year summary.
AB  - This is the 25th report prepared by the American Academy of Family Physicians
      (AAFP) on the percentage of each US medical school's graduates entering family
      medicine residency programs. Approximately 8.4% of the 16,066 graduates of US
      medical schools between July 2004 and June 2005 were first-year family medicine
      residents in 2005, compared with 9.2% in 2004 and 9.3% in 2003. Medical school
      graduates from publicly funded medical schools were more likely to be first-year
      family medicine residents in October 2005 than were residents from privately
      funded schools, 9.9% compared with 5.8%. The Mountain and the West North Central
      regions reported the highest percentage of medical school graduates who were
      first-year residents in family medicine programs in October 2005 at 13.3% and
      12.7%, respectively; the New England and Middle Atlantic regions reported the
      lowest percentages at 5.2% and 5.6%, respectively. Nearly half of the medical
      school graduates (47.3%) entering a family medicine residency program as first
      year residents in October 2005 entered a program in the same state where they
      graduated from medical school. The percentages for each medical school have
      varied substantially from year to year since the AAFP began reporting this
      information. This article reports the average percentage for each medical school
      for the last 3 years. Also reported are the number and percentage of graduates
      from colleges of osteopathic medicine who entered Accreditation Council for
      Graduate Medical Education-accredited family medicine residency programs, based
      on estimates provided by the American Association of Colleges of Osteopathic
      Medicine.

PMID- 17009188
TI  - Results of the 2006 National Resident Matching Program: family medicine.
AB  - The results of the 2006 National Resident Matching Program (NRMP) reflect a
      currently stable level of student interest in family medicine residency training
      in the United States. Compared with the 2005 Match, 26 more positions (with the
      same number of US seniors) were filled in family medicine residency programs
      through the NRMP in 2006, at the same time as four more (five fewer US seniors)
      in primary care internal medicine, one fewer in pediatrics-primary care (12 more
      US seniors), and four more (19 more US seniors) in internal medicine-pediatric
      programs. Many different forces, including student perspectives of the demands,
      rewards, and prestige of the specialty; the turbulence and uncertainty of the
      health care environment; lifestyle issues; and the impact of faculty role models
      continue to influence medical student career choices. Two more positions (nine
      more US seniors) were filled in categorical internal medicine. Two fewer
      positions (11 fewer US seniors) were filled in categorical pediatrics programs.
      The 2006 NRMP results suggest that interest in family medicine and primary care
      careers continues to be stable. With the needs of the nation calling for the
      roles and services of family physicians, family medicine matched too few
      graduates through the 2006 NRMP to meet the nation's needs for primary care
      physicians.

PMID- 17009189
TI  - Web-based versus face-to-face learning of diabetes management: the results of a
      comparative trial of educational methods.
AB  - BACKGROUND AND OBJECTIVES: Relatively little is known about the effectiveness of
      Web-based learning (WBL) in medical education and how it compares to conventional
      methods. This study examined the influence of an interactive, online curriculum
      in a third-year medical school family medicine clerkship on students' ability to
      create a management plan for a patient newly diagnosed with type 2 diabetes. We
      also evaluated how the online curriculum compared to a conventionally taught
      curriculum. METHODS: The online course included three integrated activities: (1)
      self-study modules, (2) a patient case study, and (3) a moderated discussion
      board for posting and discussing patient care plans. The WBL curriculum was
      compared to small-group case-based sessions with a faculty facilitator. Students
      completed a test case before and after the clerkship. RESULTS: Among standard-of
      care diabetic management interventions not ordered on the pretest, 38% were
      subsequently correctly ordered by WBL students on the posttest, versus 33% by
      students in the comparison group. For four out of five subgroups assessed on the
      case write-ups, the gain from before to after the clerkship favored the WBL
      group. CONCLUSIONS: Improvement among students learning online exceeded that of
      students learning face to face. This suggests superiority of the online method, a
      finding consistent with other recently published, well-controlled studies.

PMID- 17009190
TI  - Rural-urban differences in depression prevalence: implications for family
      medicine.
AB  - BACKGROUND AND OBJECTIVES: Rural populations experience more adverse living
      circumstances than urban populations, but the evidence regarding the prevalence
      of mental health disorders in rural areas is contradictory. We examined the
      prevalence of depression in rural versus urban areas. METHODS: We performed a
      cross-sectional study using the 1999 National Health Interview Survey (NHIS). In
      face-to-face interviews, the NHIS administered the Composite International
      Diagnostic Interview Short Form (CIDI-SF) depression scale to a nationally
      representative sample of 30,801 adults, ages 18 and over. RESULTS: An estimated
      2.6 million rural adults suffer from depression. The unadjusted prevalence of
      depression was significantly higher among rural than urban populations (6.1%
      versus 5.2% ). After adjusting for rural/urban population characteristics,
      however, the odds of depression did not differ by residence. Depression risk was
      higher among persons likely to be encountered in a primary care setting: those
      with fair or poor self-reported health, hypertension, with limitations in daily
      activities, or whose health status changed during the previous year. CONCLUSIONS:
      The prevalence of depression is slightly but significantly higher in residents of
      rural areas compared to urban areas, possibly due to differing population
      characteristics.

PMID- 17009192
TI  - Nine words.

PMID- 17009191
TI  - Partnerships creating postgraduate family medicine in Kenya.
AB  - Culminating a decade-long process, the first family medicine residency program in
      Kenya, among the first in Africa outside Nigeria and South Africa, was launched
      in 2005. Three diverse stakeholders are collaborating in their individual and
      joint missions: Moi University Faculty of Health Sciences (MUFHS), educating
      medical students to serve rural Kenyans; the Institute of Family Medicine (Infa
      Med), a church hospital-based non-governmental organization aiming to introduce
      family medicine in Kenya; and the Ministry of Health (MoH), working to create an
      efficient government health care workforce for 32 million Kenyans. MUFHS brings
      central facilities, enthusiastic academic leadership, and long-term vision. Infa
      Med contributes start-up resources, expatriate family medicine faculty, and well
      established hospitals for training. MoH is giving political support to the new
      specialty as well as scholarships to MoH medical officers entering the 3-year
      residency program leading to the degree of Master of Medicine in Family Health.
      Among the lessons learned through this process are the importance of melding the
      missions of all partners, of integrating clinical with community care of the
      underserved, and of deriving curriculum from African and international evidence
      on how to marshal available resources to meet Kenya's national needs.
      Opportunities continue for internal and international collaboration.

PMID- 17009194
TI  - Impacts of operative delivery for the first twin on neonatal outcomes in the
      second twin.
AB  - We assess the impacts of operative delivery for the first twins with vertex
      presentation on neonatal outcomes in second twins using the 1995 to 1997 twin
      registry data of the United States. A total of 102,554 eligible twin pairs with
      vertex presentation for the first twin were included in the analysis. Of these,
      50,748 (49.5%) first twins had a normal vaginal delivery, 43,504 (42.4%) were
      delivered by cesarean section, and 8302 (8.1%) were delivered by vaginal
      operation (vacuum extraction or forceps). In term twins, the risks of asphyxia
      related mortality (odds ratio [OR], 3.08; 95% CI, 1.07 to 8.45), newborn injury
      (OR, 2.10; 95% 1.39 to 3.12), low Apgar score at 5 minutes (OR, 1.49; 95% 1.24 to
      1.78), and mechanical ventilation use (OR, 1.34; 95% 1.20 to 1.51) were increased
      in the second twins whose co-twins were delivered by vaginal operation compared
      with those whose co-twins who had normal vaginal delivery. In contrast, the risks
      of asphyxia-related mortality (OR, 0.55; 95% 0.17 to 1.57), newborn injury (OR,
      0.20; 95% 0.11 to 0.34), low Apgar score at 5 minutes (OR, 0.51; 95% 0.44 to
      0.60), and mechanical ventilation use (OR, 0.77; 95% 0.71 to 0.83) were decreased
      in the second twins whose co-twins were delivered by cesarean section compared
      with those whose co-twins had a normal vaginal delivery. In conclusion, vaginal
      operative delivery for the first twins is related to the adverse neonatal
      outcomes of their co-twins, whereas cesarean delivery for the first twins is
      associated with the beneficial neonatal outcomes of their co-twins.

PMID- 17009195
TI  - Association of necrotizing enterocolitis with elective packed red blood cell
      transfusions in stable, growing, premature neonates.
AB  - The purpose of this study was to determine an association between packed red
      blood cell (PRBC) transfusions for anemia and necrotizing enterocolitis (NEC) in
      a subset of stable, growing, premature neonates. As part of a survey of current
      clinical practices over a 17-month period from June 1999 to October 2000, a chart
      review was performed to determine the relationship between elective PRBC
      transfusions and the occurrence of NEC. Demographic data were tabulated and
      compared between the NEC patients with a prior history of immediate blood
      transfusion (within 48 hours of onset of symptoms) and those NEC patients without
      a prior history of immediate blood transfusion. A total of 908 (inborn) neonatal
      admissions had received 751 PRBC transfusions during the study period; of these,
      17 patients (1.8%) had developed radiographic, clinical, or surgical signs of
      NEC. Six cases of NEC (35%; six of 17 patients) were associated with PRBC
      transfusions (0.8%; six of 751 transfusions). The transfusion-associated NEC
      group developed presenting signs within 22 +/- 5 hours (median, 19; range, 12 to
      38) of a PRBC transfusion at a mean age of 32 +/- 7 days. In contrast, the non
      transfusion-associated NEC group (n = 11) had onset of NEC at a mean age of 12 +/
      7 days ( P < 0.05) after 185 +/- 91 hours (median, 180; range, 96 to 312; P <
      0.02] of a transfusion. Prior to the onset of NEC, all of the neonates in the
      transfusion-associated NEC group were stable, growing, not ventilated, receiving
      full enteral feedings, and had no other active medical problems except anemia
      (hematocrit, 24 +/- 3%). In contrast, the nontransfusion NEC group was more often
      ventilated, was receiving < 50% of fluids by mouth, had lower Apgar scores, and
      was transfused for an average hematocrit of 37 +/- 7% ( P < 0.05). There was no
      significant difference in the type, storage, volume, or preservative used between
      the blood products in the two groups. We identified an unanticipated relationship
      between late-onset NEC in stable, growing, premature neonates who were transfused
      electively for anemia of prematurity.

PMID- 17009196
TI  - A standardized method for assigning gestational age: a tool for measuring
      gestational age based newborn intensive care outcomes.
AB  - We developed a computer-generated algorithm for standardizing the assignment of a
      best gestational age. Our database collected information on maternal last
      menstrual period (LMP), prenatal ultrasonography, obstetrical estimated date of
      confinement (EDC), use of assisted reproductive technology (ART), and newborn
      assessment based on the Ballard examination. The algorithm for determining best
      gestational age was developed based on the literature on the accuracy of prenatal
      and neonatal dating. We examined the performance of the algorithm using patients
      admitted to our neonatal intensive care unit (NICU) with a best gestational age
      <or= 32 completed weeks. Based on agreement of the obstetric EDC with either the
      first-trimester ultrasonography or LMP and first- and second-trimester
      ultrasonography, 64.4% of patients were classified as having certain dating. The
      Ballard assessment played a role in assigning a best gestational age in 11.3% of
      patients. We demonstrated differences in outcomes based on dating certainty
      within subpopulations in our NICU. An objective standardized methodology for
      assigning gestational age is a useful tool for comparing gestational age-based
      outcome measures between institutions.

PMID- 17009197
TI  - Hyperexcitability syndrome in a newborn infant of chocoholic mother.
AB  - We present a case of hyperexcitability syndrome observed in a neonate born to a
      mother who was a heavy user of cocoa and chocolate during pregnancy and
      lactation. The infant presented jitteriness, irritability, inconsolable crying,
      excessive sucking, and sleeping difficulties almost immediately after birth. The
      infant underwent extensive diagnostic studies, but none of the usual causes for
      its symptoms were identified. The symptoms resolved after the interruption of
      maternal chocolate consumption. We hypothesize that the heavy exposure to
      chocolate could be responsible for the hyperexcitability syndrome.

PMID- 17009198
TI  - Free carnitine levels in respiratory distress syndrome during the first week of
      life.
AB  - Antenatal carnitine administration has been shown to induce fetal lung maturity
      by increasing pulmonary surfactant in animal and human studies. The aim of this
      study was to investigate serum free carnitine (FC) levels in preterm infants with
      respiratory distress syndrome (RDS) and controls during the first week of
      postnatal life. The study groups consisted of 76 preterm infants with gestational
      ages ranging from 28 to 36 weeks, and birthweights ranging from 1046 to 2352 g.
      Serum FC levels were measured in preterm infants (group A, 37 with RDS; group B,
      39 controls without RDS) within the first 6 hours after birth, on days 3 and 7.
      For specific analyses, serum FC levels were determined for gestational ages 28 to
      31 weeks and 32 to 36 weeks in both groups. Initial FC levels were decreased
      insignificantly in group A (22.5 +/- 7.3 micromol/L) compared with group B (23.5
      +/- 6.8 micromol/L; P > 0.05). On days 3 and 7 of life, serum FC levels were
      significantly lower in group A (18.3 +/- 6.1 and 10.2 +/- 3.3 micromol/L,
      respectively) than in group B (23.4 +/- 7.1 and 22.8 +/- 3.7 micromol/L,
      respectively; P < 0.05 and P < 0.05, respectively) on days 3 and 7 of life,
      respectively. Serum FC level remained stable in the non-RDS group ( P > 0.05),
      but it decreased significantly in the RDS group during the first week of
      postnatal life ( P < 0.05). No differences were seen between the corresponding
      gestational age groups. Serum FC levels in RDS infants decreased from days 1 to
      7. Decreased neonatal serum carnitine levels in preterm infants with RDS during
      the first week of life might be caused by increasing consumption of carnitine in
      lung tissue for surfactant synthesis.

PMID- 17009203
TI  - Modulation of selenite cataract by the flavonoid fraction of Emilia sonchifolia
      in experimental animal models.
AB  - The purpose of the study was to investigate the role of flavonoids from Emilia
      sonchifolia (ES) on the progression of selenite-induced cataract. The antioxidant
      property of the flavonoids isolated from ES was assessed by measuring its
      capacity to inhibit superoxide production and serum oxidation in vitro in
      comparison with quercetin. Based on these experiments, an in vivo study was
      conducted to evaluate the modulatory effects of the flavonoids against selenite
      cataract. Cataract was induced by a single subcutaneous injection of sodium
      selenite (4 mg/kg body weight). The treatment group received flavonoids from ES
      (1 mg/kg) and this was compared with the quercetin treated group. Lens
      opacification was monitored by a slit lamp microscope and classified into six
      stages. Activity of the antioxidant enzymes - superoxide dismutase and catalase -
      and the level of lipid peroxidation products thiobarbituric acid reacting
      substances and reduced glutathione were studied. Slit lamp examination showed
      that the flavonoid fraction from ES could modulate the progression of cataract.
      Activities of superoxide dismutase, catalase and reduced glutathione were found
      to be increased in the ES treated groups, while thiobarbituric acid reacting
      substances were decreased compared with the selenite-induced group. The results
      suggest that flavonoids from ES can modulate lens opacification and oxidative
      stress in selenite-induced cataract.

PMID- 17009205
TI  - Antimicrobial activity of two wild mushrooms Clitocybe alexandri (Gill.) Konr.
      and Rhizopogon roseolus (Corda) T.M. Fries collected from Turkey.
AB  - Two edible wild mushrooms, namely Clitocybe alexandri (Gill.) Konr.
      (Tricholomataceae) and Rhizopogon roseolus (Corda) T.M. Fries (Rhizopogonaceae),
      collected from the southwest of Turkey, were tested for their antimicrobial
      activity by using the disc diffusion method. The ethanol, methanol, diethyl
      ether, water, ethylacetate and n-hexane extracts from the fruit bodies of
      mushrooms were assayed against 13 microorganisms. In comparison with the test
      antibiotics penicillin, novobiocin, nalidixic acid and ampicillin, the methanol
      extract obtained from the two mushrooms presented significant activity against E.
      coli, Bacillus subtilis and Enterobacter aerogenes. On the other hand, the
      ethylacetate extract from C. alexandri was found to be active against Candida
      albicans and Saccharomyces cerevisiae, whereas the ethanol extract of Rhizopogon
      roseolus was active against Saccharomyces cerevisiae. This research has shown
      that various extracts obtained from two macrofungi could be used in vitro to
      inhibit the growth of some important bacteria and fungi.

PMID- 17009204
TI  - Larvicidal activity of some Labiatae (Lamiaceae) plant extracts from Turkey.
AB  - Ethanol extracts of the aerial parts from five Labiatae (Lamiaceae) species,
      obtained from Antalya, Turkey, were tested for larvicidal activity against the
      house mosquito Culex pipiens L. (Diptera: Culicidae) under laboratory conditions.
      Third and fourth instar mortality from six concentrations (5, 10, 25, 50, 100 and
      200 ppm) of each plant extract were compared against the organophosphorus
      insecticide, temephos which is currently used for larval control. All plant
      extracts showed high larvicidal activity in 24 h exposure tests. Teucrium
      divaricatum Sieber was the most toxic, followed by Mentha longifolia (L.) Huds.,
      Melissa officinalis L., Salvia sclarea L. and Mentha pulegium L. with LC(50)
      values of 18.6, 26.8, 39.1, 62.7 and 81.0 ppm, respectively. This study is the
      first to report on the larvicidal activity of ethanol extracts of these five
      plant species against C. pipiens.

PMID- 17009206
TI  - Antispasmodic effect of Acorus calamus Linn. is mediated through calcium channel
      blockade.
AB  - Acorus calamus Linn. (Araceae) is a native of Central Asia and Eastern Europe and
      has widespread use in the traditional system of medicine for gastrointestinal
      disorders such as colic pain and diarrhoea. This study was aimed at providing a
      possible pharmacological basis to the use of this plant as an antispasmodic and
      antidiarrhoeal. In the isolated rabbit jejunum preparation the crude extract
      (Ac.Cr), which tested positive for the presence of alkaloid, saponins and
      tannins, caused inhibition of spontaneous and high K(+) (80 mm)-induced
      contractions, with respective EC(50) values of 0.42 +/- 0.06 and 0.13 +/- 0.04
      mg/mL (mean +/- SEM; n = 6-8), thus showing spasmolytic activity, mediated
      possibly through calcium channel blockade (CCB). The CCB activity was confirmed
      when pre-treatment of the tissue with Ac.Cr (0.3-1.0 mg/mL) caused a rightward
      shift in the Ca(++) dose-response curves similar to that caused by verapamil, a
      standard calcium channel blocker. Activity-directed fractionation revealed that
      the CCB activity was concentrated in the n-hexane fraction while the ethylacetate
      fraction was less potent. These results suggest that the spasmolytic effect of
      the plant extract is mediated through the presence of CCB-like constituent(s)
      which is concentrated in the n-hexane fraction and this study provides a strong
      mechanistic base for its traditional use in gastrointestinal disorders such as
      colic pain and diarrhoea.

PMID- 17009207
TI  - Acceleration of lipid degradation by sericoside of Terminalia sericea roots in
      Fully differentiated 3T3-L1 cells.
AB  - Sericoside is a traditional herbal saponin from Terminalia sericea (Family
      Combretaceae). The influence of sericoside on lipolysis was studied in fully
      differentiated 3T3-L1 cells, and glycerol release into the cytosol and residual
      triglyceride were measured. The addition of sericoside stimulated glycerol
      release into the cytosol from deposited triglyceride in a dose- and time
      dependent manner. These data suggested that sericoside has a strong lipolytic
      activity.

PMID- 17009208
TI  - Echinacea extracts modulate the production of multiple transcription factors in
      uninfected cells and rhinovirus-infected cells.
AB  - Extracts of Echinacea purpurea are widely used for the prevention and treatment
      of common colds, coughs, bronchitis and other upper respiratory infections, many
      of which are caused by rhinoviruses (RVs). Recent reports have indicated that
      rhinoviruses can stimulate the release of various pro-inflammatory cytokines and
      chemokines from cultured nasal and bronchial human epithelial cells, and several
      transcription factors (TFs) have been implicated in this process. The effects of
      Echinacea treatment and rhinovirus infection on the activation of a range of
      transcription factors were evaluated by means of a protein/DNA array analysis.
      The BEAS-2B cell line was used as the model, and nuclear extracts of uninfected
      cells and rhinovirus-14 infected cells were examined with and without treatment
      with one of two chemically different Echinacea extracts. It was found that both
      Echinacea extracts increased the nuclear content of more than 30 transcription
      factors, including the 12 pro-inflammatory factors examined, such as NFkB, AP-1,
      AP-2 and STATs 1-6. Virus infection resulted in a more dramatic increase in these
      same TFs. However, when RV-infected cells were treated with either of the two
      Echinacea extracts, TF levels were reduced to low levels, although the pattern of
      the reductions was different for the two extracts. These results indicate that
      rhinovirus infection of epithelial cells, and treatment with Echinacea extracts,
      led to profound effects on numerous transcription factors, which could explain
      the previously observed modulation of secreted cytokines and chemokines, as well
      as other signaling pathways. In addition, the results could help to explain the
      beneficial effects of Echinacea consumption.

PMID- 17009209
TI  - Neuropharmacological evaluation of the putative anxiolytic effects of Passiflora
      edulis Sims, its sub-fractions and flavonoid constituents.
AB  - Passiflora edulis Sims together with several other plants of the genus Passiflora
      have been reported to possess anxiolytic properties. It has been suggested
      recently that flavonoids may be partly responsible for the neuropharmacological
      activity of these plants but there are still few data reporting the relation
      between the constituents of these plants and their activity. This work evaluated
      the anxiolytic/sedative activity of an aqueous extract of Passiflora edulis Sims
      and bioguided its fractionation using the elevated plus-maze model of anxiety and
      other complementary pharmacological tests. The aqueous extract presented an
      anxiolytic-like activity without any significant effect upon the motor activity
      whilst the total flavonoid fraction (TFF) presented an anxiolytic-like activity
      but compromised motor activity. Through fractionation of TFF it was possible to
      isolate and characterize luteolin-7-O-[2-rhamnosylglucoside] which showed an
      anxiolytic-like activity without compromising motor activity.

PMID- 17009211
TI  - Risk assessments of polychlorinated dibenzo- p-dioxins, polychlorinated
      dibenzofurans, and dioxin-like polychlorinated biphenyls in food.
AB  - The polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans
      (PCDF), and dioxin-like polychlorinated biphenyls (dioxin-like PCB) are
      ubiquitous in food of animal origin and accumulate in fatty tissues of animals
      and humans. The most toxic congener is 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD). The toxic responses include dermal toxicity, immunotoxicity,
      carcinogenicity, and reproductive and developmental toxicity. Toxic equivalency
      factors have been established for the other PCDD, PCDF and dioxin-like PCB
      relative to TCDD, and the combined toxicity of a sample can be expressed as toxic
      equivalent (WHO-TEQ). The EC Scientific Committee for Food evaluated these
      compounds in 2001. The assessment used the most sensitive adverse toxicological
      end-points of TCDD in experimental animals. These were developmental and
      reproductive effects in the male offspring of rats administered TCDD during
      pregnancy. Because of the large difference between rats and humans in the
      biological half-life of TCDD, the assessment used a body burden approach to
      compare across species and derived a tolerable weekly intake of 14 pg TCDD/kg of
      body weight (bw), which was extended to include all the 2,3,7,8-substituted PCDD
      and PCDF, and the dioxin-like PCB, and expressed as a group tolerable weekly
      intake of 14 pg WHO-TEQ/kg bw. The FAO/WHO Joint Expert Committee on Food
      Additives (JECFA) performed a similar assessment whereas the US Environmental
      Protection Agency (US EPA) has paid more attention to human data on
      carcinogenicity.

PMID- 17009212
TI  - Current dietary exposure to polychlorodibenzo-p-dioxins, polychlorodibenzofurans,
      and dioxin-like polychlorobiphenyls in Italy.
AB  - This study deals with an assessment of dietary exposure to polychlorodibenzo-p
      dioxins (PCDDs), polychlorodibenzofurans (PCDFs), and dioxin-like
      polychlorobiphenyls (DL-PCBs) for the Italian general population, obtained by
      combining data from a national food consumption survey with contamination
      concentrations of European foodstuffs available on the market. The distribution
      of PCDD, PCDF, and DL-PCB dietary intake(s) in the Italian population was
      investigated to assess to what extent the variability in dietary habits may cause
      higher exposures to the previously mentioned contaminants. Results indicate that
      the main contributions to total PCDD, PCDF, and DL-PCB intake are due to fish and
      fish products (44%) and to milk and dairy products (27%). The mean PCDD, PCDF,
      and DL-PCB intake (total toxic equivalents) via food was estimated 5.34, 3.37,
      and 2.28 pg World Health Organization (WHO)-TE/kg of body weight (kg-bw) per day
      for the three age groups 0-6 (breastfeeding excluded), 7-12, and 13-94 years old,
      respectively. The highest exposures due to variation in dietary habits are in
      general within a factor of 2-3. From the mean exposure estimated for the general
      population (adults), it can be inferred that a consistent part of it would exceed
      the tolerable daily intake of 2 pg WHO-TE/kg-bw adopted by the Scientific
      Committee on Food of the European Commission in 2001.

PMID- 17009213
TI  - Dioxins, polychlorinated biphenyls and other organohalogen compounds in human
      milk. Levels, correlations, trends and exposure through breastfeeding.
AB  - Polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF), together
      simplified termed "dioxins", polychlorinated biphenyls (PCB), polybrominated
      diphenylethers (PBDE) and organochlorine pesticides constitute lipophilic,
      persistent organic pollutants that bioaccumulate in the food chain and
      consequently can be found in humans at considerable concentrations. During the
      past 30 years our institute analyzed far more than 2,000 individual human milk
      samples for organochlorine pesticides and PCB and over 1,000 specimens for
      PCDD/PCDF. The results of these analyses provide an overview and reliable basis
      as to contamination of human milk with these compounds, their correlations among
      each other, the temporal trend of exposure through breastfeeding and the
      predominant parameters that influence the maternal body burden. It was found that
      the levels of most persistent organohalogen compounds in human milk decreased
      significantly over the past three decades and equally did their exposure through
      breastfeeding. Exceptions are PBDE, which are still extensively used as flame
      retardants. PBDE levels in milk samples collected in the early 2,000s are
      approximately 60% higher compared to specimens sampled 10 years before. Moreover,
      in contrast to PCB, PBDE show no significant correlation with PCDD/PCDF in human
      milk, which might be interpreted as an indication for another mode of human
      exposure.

PMID- 17009214
TI  - The use of the DR CALUX bioassay and indicator polychlorinated biphenyls for
      screening of elevated levels of dioxins and dioxin-like polychlorinated biphenyls
      in eel.
AB  - The DR CALUX bioassay is a very suitable screening method for dioxins and dioxin
      like-PCBs in feed and food. This was, e. g. demonstrated in a survey in the
      Netherlands to control the dioxin levels in eel. The DR CALUX assay, but also
      indicator polychlorinated biphenyls (PCB) were evaluated as a screening method.
      Based on the limit for polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/F)
      [at that time 8 pg toxic equivalents (TEQ)/g eel], and the relation between
      PCDD/F and dioxin-like-PCB, a decision limit of 30 pg TEQ/g eel was used for
      screening of 153 field samples. Suspected samples (21) and part of the higher
      contaminated negative samples (35) were analyzed by GC/MS for dioxins, non-ortho,
      mono-ortho and indicator PCB, revealing 13 samples exceeding the action limit of
      30 pg TEQ/g eel. Only one sample slightly exceeded the dioxin level of 8 pg TEQ/g
      eel. The relatively low sensitivity for mono-ortho PCB was overcome by the use of
      reference samples, as shown by the correlation of 0.93 between GC/MS and CALUX
      determined total TEQ levels. The present data show that the DR CALUX assay can be
      used for screening of total TEQ levels in eel. The use for dioxins only requires
      a safe, and therefore relatively low, decision limit. The indicator PCB also
      showed a good correlation with total TEQ levels, mainly due to the large
      contribution of the mono-ortho PCB at higher concentrations. The relation with
      dioxins was very poor and as such indicator PCB seem less suitable than the DR
      CALUX assay for screening for dioxins only. The present study clearly shows that
      part of the wild eel samples contains high total TEQ levels and will exceed the
      future European Union limit of 12 pg TEQ/g eel for dioxins and dioxin-like PCB.
      Especially at high TEQ levels, dioxin-like PCB contribute most to the total TEQ.
      In practice, wild eel presents only a minor part of the eel consumed.

PMID- 17009215
TI  - Proximate composition, fatty acid analysis and protein digestibility-corrected
      amino acid score of three Mediterranean cephalopods.
AB  - Proximate composition, fatty acid analysis and protein digestibility-corrected
      amino acid score (PDCAAS) in three commercially important cephalopods of the
      Mediterranean sea (cuttlefish, octopus and squid) were determined. The results of
      the proximate analysis showed that these species had very high protein:fat ratios
      similar to lean beef. Docosahexaenoic, palmitic and eicosipentaenoic acid were
      the most abundant fatty acids among analyzed species. The amount of n-3 fatty
      acids was higher than that of saturated, monounsaturated and n-6 fatty acids.
      Despite the fact that cephalopods contain small amounts of fat they were found
      quite rich in n-3 fatty acids. Finally, PDCAAS indicated that these organisms had
      a very good protein quality.

PMID- 17009219
TI  - Peripheral T-cell lymphoma in a five year old.
AB  - We report a case presenting with persistent pyrexia that led to the diagnosis of
      peripheral T-cell lymphoma, a rare malignancy in childhood. The case illustrates
      diagnostic conundrums in a patient who is not responding as expected to
      treatment.

PMID- 17009220
TI  - Young siblings of children with cancer deserve care and a personalized approach.
AB  - The youngest siblings may be both emotionally vulnerable and often neglected
      members of the family of a childhood cancer patient. The prompt identification of
      signs of distress in these subjects allows trained caregivers to intervene with
      personalized, age-appropriate, attention, and care. A narrative approach, based
      on personalized listening, writings, and spontaneous drawings, can provide the
      means to elicit markers of psychological maladjustment in even the youngest of
      siblings. Two exemplary cases are reported to illustrate this approach.

PMID- 17009221
TI  - Concurrent carbogen and radiation therapy in children with high-risk brainstem
      gliomas.
AB  - In an attempt to improve local control, we assessed the feasibility of the
      addition of 4 min of carbogen inhalation (as a radiosensitizer) to daily
      fractionated radiotherapy in pediatric patients with high grade and/or diffuse
      brainstem gliomas. Ten patients inhaled carbogen for >90% of the radiation
      treatments. Median survival time from start of therapy was 0.80 years. Carbogen
      inhalation did not appear to improve the dismal prognosis.

PMID- 17009223
TI  - Antimalarial agents: closing the gate on Toll-like receptors?

PMID- 17009224
TI  - Therapy for giant cell arteritis: can we do better?

PMID- 17009225
TI  - Stemming cartilage degeneration: adult mesenchymal stem cells as a cell source
      for articular cartilage tissue engineering.

PMID- 17009226
TI  - Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory
      arthritis.

PMID- 17009227
TI  - Influence of male sex on disease phenotype in familial rheumatoid arthritis.
AB  - OBJECTIVE: To examine sex differences in clinical, demographic, and genetic
      characteristics among a large cohort of patients with familial rheumatoid
      arthritis (RA). METHODS: We studied 1,004 affected members of 467 Caucasian
      multicase RA families recruited from the North American Rheumatoid Arthritis
      Consortium. Standardized information about demographic and clinical
      characteristics was collected from all patients. Affected individuals also
      underwent radiography of the hands and were genotyped for markers in the HLA
      region. Sex differences were assessed using contingency table analysis (for
      categorical variables) and Student's t-tests for (continuous variables), and by
      multivariate logistic and linear regression analysis. RESULTS: Male patients had
      a significantly later onset of RA, were more likely to be seropositive for RF,
      and had significantly higher titers of anti-cyclic citrullinated peptide (anti
      CCP) antibodies compared with female patients, even after adjustment for
      covariates in multivariate analyses. Male patients were also significantly more
      likely to have a history of smoking and to be HLA-DRB1 shared epitope (SE)
      positive. Interestingly, female patients with an affected male sibling had
      significantly higher titers of anti-CCP antibodies and were more likely to be SE
      positive compared with female patients without affected male siblings.
      Multivariate analyses indicated that the presence of the SE did not fully explain
      the increased anti-CCP antibody titers observed in these families. CONCLUSION:
      Sex has an important influence on the disease phenotype in RA, including the age
      at disease onset and autoantibody production. Furthermore, families with affected
      male members are characterized by higher titers of autoantibodies, particularly
      anti-CCP antibodies. Our results indicate that these findings are not fully
      explained by differences in exposure to tobacco smoke, presence of the HLA-DRB1
      SE, or other HLA region genetic variation. Thus, other genetic or nongenetic
      factors also contribute to sex differences in the RA phenotype.

PMID- 17009228
TI  - Pharmacogenomic and metabolic biomarkers in the folate pathway and their
      association with methotrexate effects during dosage escalation in rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate the contribution of metabolites (methotrexate [MTX] and
      folate polyglutamate [PG] levels) and pharmacogenetic biomarkers in the folate
      pathway to the effects of MTX in patients with rheumatoid arthritis not
      previously treated with this antifolate. METHODS: Forty-eight MTX-naive adult
      patients were enrolled in a prospective longitudinal study. MTX therapy was
      initiated at 7.5 mg/week and was increased every 4-6 weeks until a therapeutic
      response was achieved. Response was assessed using the Disease Activity Score in
      28 joints (DAS28). Red blood cell (RBC) MTX and folate PG levels were measured
      with 9 common polymorphisms in the folate pathway. Statistical analyses consisted
      of generalized linear models and multivariate regressions. RESULTS: After 6
      months of therapy, the median weekly MTX dosage was 17.5 mg and the median
      decrease in the DAS28 was 2.0. There was a large interpatient variability in RBC
      MTXPG levels (median 35 nmoles/liter [interquartile range 28-51] at month 6).
      Patients with a lesser decrease in the DAS28 (fewer improvements) had lower RBC
      MTXPG levels (P < 0.05) despite the higher MTX dose administered (P < 0.05). RBC
      folate PG levels decreased significantly during treatment, and a lesser decrease
      in RBC folate PGs was associated with a lesser decrease in the DAS28 (P < 0.05).
      Primary side effects were gastrointestinal and neurologic in nature. Risk
      genotypes associated with toxicity were in gamma-glutamyl hydrolase (-401CC), 5
      aminoimidazole-4-carboxamide ribonucleotide transformylase (347GG),
      methylenetetrahydrofolate reductase (1298AC/CC), methionine synthase (2756AA),
      and methionine synthase reductase (66GG). CONCLUSION: RBC MTXPG levels are a
      useful means by which to monitor therapy. The genetic associations presented
      generate hypotheses, and confirmation in independent cohorts is warranted.

PMID- 17009229
TI  - Clinical assessment of the long-term risk of fracture in patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) have an
      increased risk of fracture, and to estimate their long-term absolute fracture
      risk. METHODS: We studied patients with RA ages >or=40 years in the British
      General Practice Research Database, each matched by age, sex, calendar time, and
      practice to 3 control patients. Incident fractures, as recorded in the
      computerized medical records, were ascertained over a median followup of 7.6
      years. The fracture rate in RA patients compared with controls was adjusted for
      smoking, body mass index (BMI), and several clinical risk factors, and Cox
      proportional hazards models were used to calculate the relative risk (RR) of
      fracture in RA. A risk score was then developed to provide an estimate of the 5-
      and 10-year fracture risk among RA patients. RESULTS: There were 30,262 patients
      with RA, of whom 2,460 experienced a fracture during followup. Compared with
      controls, patients with RA had an increased risk of fracture, which was most
      marked at the hip (RR 2.0, 95% confidence interval [95% CI] 1.8-2.3) and spine
      (RR 2.4, 95% CI 2.0-2.8). Indicators of a substantially elevated risk of fracture
      (at the hip) included >10 years' duration of RA (RR 3.4, 95% CI 3.0-3.9), low BMI
      (RR 3.9, 95% CI 3.1-4.9), and use of oral glucocorticoids (RR 3.4, 95% CI 3.0
      4.0). Modeling of the long-term risk profiles revealed that, for example, in a
      woman age 65 years with longstanding RA whose risk factors also included low BMI,
      a history of fracture, and frequent use of oral glucocorticoids, the 5-year risk
      of hip fracture was 5.7% (95% CI 5.3-6.1%). CONCLUSION: Patients with RA are at
      increased risk of osteoporotic fractures. This increased risk is attributable to
      a combination of disease activity and use of oral glucocorticoids.

PMID- 17009230
TI  - Disconnect between inflammation and joint destruction after treatment with
      etanercept plus methotrexate: results from the trial of etanercept and
      methotrexate with radiographic and patient outcomes.
AB  - OBJECTIVE: To determine the relationship between disease activity and
      radiographic progression of joint destruction in patients with rheumatoid
      arthritis (RA) treated with methotrexate (MTX), those treated with etanercept,
      and those treated with the combination of MTX plus etanercept. METHODS: Baseline,
      12-month, and 24-month data from the Trial of Etanercept and Methotrexate with
      Radiographic and Patient Outcomes database were analyzed. The dependent variable
      was the 1-year change in the modified Sharp/van der Heijde score (Sharp score);
      therefore, 2 interval changes per patient were available. Interval change in the
      Sharp score was modeled by time (years), treatment, disease activity, and the
      interaction (disease activity x treatment). Disease activity was reflected by the
      time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive
      protein (taCRP) level, which were calculated per 1-year interval. Generalized
      mixed linear modeling (GMLM) was used to adjust for within-patient correlation.
      RESULTS: GMLM confirmed a significant interaction between treatment and the taCRP
      level and taDAS with respect to the change in Sharp score (P = 0.012 and P =
      0.03, respectively). In patients treated with MTX alone, radiographic progression
      increased with an increasing taCRP level or taDAS, although progression rates
      were low in patients whose disease was in remission and in those with low-to
      moderate disease activity. This relationship was less clear in patients treated
      with etanercept and was absent in those who received combination therapy.
      CONCLUSION: Combination therapy with MTX plus etanercept uncouples the classic
      relationship between disease activity and radiographic progression in patients
      with RA.

PMID- 17009231
TI  - Changes in Health Assessment Questionnaire disability scores over five years in
      patients with rheumatoid arthritis compared with the general population.
AB  - OBJECTIVE: To analyze longitudinal data over 5 years for changes in Health
      Assessment Questionnaire (HAQ) scores in patients with rheumatoid arthritis (RA)
      and age- and sex-matched controls from the general population. METHODS: In 2000
      and 2005, identical self-report questionnaires were mailed to a cohort of
      patients with RA and control cohort from the community. The questionnaire
      included the HAQ, which was used to assess functional status. Changes in HAQ
      scores over 5 years were analyzed. RESULTS: In 2000, 73% of 1,495 patients with
      RA and 77% of 2,000 general population controls responded to the questionnaire.
      In 2005, 84% of 2,022 patients with RA and 77% of 1,817 controls responded. A
      total of 863 patients with RA and 1,176 community controls responded in both 2000
      and 2005 and were included in the analyses. Mean baseline HAQ scores were
      significantly higher in patients with RA than in controls (0.71 versus 0.17; P <
      0.001). Over 5 years, the HAQ scores increased by 0.01 units per year in both the
      RA cohort and the community population; in both cohorts, the net change was
      primarily attributable to individuals over age 70 years. Changes in HAQ scores
      were similar in patients and controls who had low HAQ scores at baseline. Female
      patients with baseline HAQ scores of >or=0.5 had less potential for improvement
      than did controls. Among subjects in both groups who had HAQ scores >2, death was
      a common outcome over the next 5 years. CONCLUSION: Currently, progression of
      functional disability among patients with RA and among persons in the general
      population is largely explained by the aging process. Our results showing stable
      function scores over 5 years in most patients with RA who are younger than age 70
      years provide further evidence of improved status of RA patients today compared
      with the major declines observed in previous decades.

PMID- 17009233
TI  - In vitro and in vivo efficacy of a recombinant immunotoxin against folate
      receptor beta on the activation and proliferation of rheumatoid arthritis
      synovial cells.
AB  - OBJECTIVE: To investigate the effects of the recombinant immunotoxin dsFv anti
      FRbeta-PE38, which consists of the disulfide-stabilized Fv fragment (dsFv) of the
      anti-folate receptor beta (anti-FRbeta) antibody and the 38-kd portion of
      Pseudomonas exotoxin A (PE38), on the activation and proliferation of cells that
      function in inflammatory and degradative processes in rheumatoid arthritis (RA)
      synovial tissue. METHODS: The Ig VH-PE38 fusion protein and the Ig VL protein
      were produced in Escherichia coli, and then joined with a disulfide bond by
      engineering cysteine residues in the framework regions of these proteins. The
      effects of dsFv anti-FRbeta-PE38 on the activation and proliferation of cells in
      RA synovial tissue were investigated by immunohistochemistry; the numbers of
      cells expressing CD68, vascular cell adhesion molecule 1, angiopoietin 1, CD34,
      proliferating cell nuclear antigen, and interleukin-6 and the numbers of
      apoptotic cells were counted in RA synovial tissue engrafted into SCID mice
      treated or not treated with dsFv anti-FRbeta-PE38. The effects of dsFv anti
      FRbeta-PE38 on the generation of osteoclasts from RA adherent synovial
      mononuclear cells in vitro was investigated by counting the number of resorption
      pits on dentin slices treated or not treated with dsFv anti-FRbeta-PE38. RESULTS:
      Administration of dsFv anti-FRbeta-PE38 reduced the numbers of macrophages,
      activated fibroblast-like cells, endothelial cells, and proliferating cells and
      increased the numbers of apoptotic cells in RA synovial tissue engrafted into
      SCID mice. In vitro, the generation of osteoclasts from RA adherent synovial
      mononuclear cells was largely suppressed by treatment with dsFv anti-FRbeta-PE38.
      CONCLUSION: Our findings show that dsFv anti-FRbeta-PE38 immunotoxin would be a
      promising tool for the treatment of RA synovitis, especially when administered
      intraarticularly.

PMID- 17009232
TI  - Brainstem primitive neuroectodermal tumors (bstPNET): results of treatment with
      intensive induction chemotherapy followed by consolidative chemotherapy with
      autologous hematopoietic cell rescue.
AB  - We have evaluated the response rate and survival utilizing intensified
      chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic
      cell rescue (AuHCR) and adjuvant radiation therapy in six young children with
      newly diagnosed brainstem primitive neuroectodermal tumors (bstPNET). Following
      maximum surgical resection of the tumor, patients received high dose induction
      chemotherapy including vincristine, cisplatin, cyclophosphamide, and etoposide.
      Eligible patients received a single cycle of myeloablative chemotherapy followed
      by AuHCR. Two patients survive at least 32 months with stable disease. This
      approach provides an alternative for young patients with bstPNET who in prior
      reports have had a uniformly fatal prognosis.

PMID- 17009234
TI  - CTLA-4IG suppresses reactive oxygen species by preventing synovial adherent cell
      induced inactivation of Rap1, a Ras family GTPASE mediator of oxidative stress in
      rheumatoid arthritis T cells.
AB  - OBJECTIVE: Oxidative stress contributes to the inflammatory properties of
      rheumatoid arthritis (RA) synovial T lymphocytes. This study was undertaken to
      investigate the mechanisms leading to production of reactive oxygen species (ROS)
      and oxidative stress in RA synovial T lymphocytes. METHODS: ROS production in T
      lymphocytes from the peripheral blood (PB) of healthy donors and from the PB and
      synovial fluid (SF) of RA patients was measured by ROS-dependent fluorescence of
      6-carboxy-2',7'-dichlorofluorescein. Rap1 GTPase activation was assessed by
      activation-specific probe precipitation. Proliferation of RA PB and SF T
      lymphocytes was assayed by 3H-thymidine incorporation. In some experiments, RA PB
      T cells were preincubated with autologous SF or with PB or SF adherent cells.
      Experiments were performed in the absence or presence of transwell membranes or
      CTLA-4Ig fusion proteins. Short- and long-term stimulations of healthy donor PB T
      lymphocytes were performed with inflammatory cytokines, in the absence or
      presence of activating anti-CD28 antibodies. RESULTS: T lymphocyte ROS production
      and Rap1 inactivation were mediated by cell-cell contact with RA synovial
      adherent cells, and this correlated with T cell mitogenic hyporesponsiveness.
      CTLA4-Ig blockade of synovial adherent cell signaling to CD28 T cells reversed
      the inhibition of Rap1 activity and prevented induction of ROS. Introduction of
      active RapV12 into T cells also prevented induction of ROS production.
      Coincubation of T cells with stimulating anti-CD28 antibodies and inflammatory
      cytokines synergistically increased T cell ROS production. CONCLUSION: Cell-cell
      contact between T cells and RA synovial adherent cells mediates Rap1 inactivation
      and subsequent ROS production in T lymphocytes following exposure to inflammatory
      cytokines. This process can be blocked by CTLA4-Ig fusion protein.

PMID- 17009235
TI  - Study on the ability of 1,2,3,4-tetrahydropapaveroline to cause oxidative stress:
      Mechanisms and potential implications in relation to parkinson's disease.
AB  - Tetrahydropapaveroline (THP) is a compound derived from dopamine monoamine
      oxidase-mediated metabolism, particularly present in the brain of parkinsonian
      patients receiving L-dopa therapy, and is capable of causing dopaminergic
      neurodegeneration. The aim of this work was to evaluate the potential of THP to
      cause oxidative stress on mitochondrial preparations and to gain insight into the
      molecular mechanisms responsible for its neurotoxicity. Our data show that THP
      autoxidation occurs with a continuous generation of hydroxyl radicals (*OH) and
      without the involvement of the Fenton reaction. The presence of ascorbate
      enhances this process by establishing a redox cycle, which regenerates THP from
      its quinolic forms. It has been shown that the production of *OH is not affected
      by the presence of either ferrous or ferric iron. Although THP does not affect
      lipid peroxidation, it is capable of reducing the high levels of thiobarbituric
      acid-reactive substances obtained in the presence of ascorbate and/or iron.
      However, THP autoxidation in the presence of ascorbate causes both an increase in
      protein carbonyl content and a reduction in protein-free thiol content. THP also
      increases protein carbonyl content when the autoxidation occurs in the presence
      of iron. The remarkable role played by ascorbate in the production of oxidative
      stress by THP autoxidation is of particular interest.

PMID- 17009236
TI  - Impact of an education program on late diagnosis of retinoblastoma in Honduras.
AB  - BACKGROUND: In developed countries, more than 90% of children with retinoblastoma
      present with limited-stage disease and are cured; however, in countries with
      limited resources, like Honduras, most patients present with advanced disease and
      cure rates are less than 50%. Early diagnosis is necessary to improve the
      survival of children with retinoblastoma in these countries. PROCEDURE: We
      describe the preliminary results of a retinoblastoma education program linked to
      a national vaccination campaign in Honduras. Posters and flyers were designed to
      be accessible to poorly educated readers, to convey the severity of
      retinoblastoma, and to provide contact information. Charts and an electronic
      database were reviewed to determine age at diagnosis, presenting signs and
      symptoms, date of diagnosis, and outcome. RESULTS: During the eight previous
      years (July 1995-June 2003), 73% of the 59 diagnosed cases of retinoblastoma were
      extraocular; in contrast, during the post-campaign period (June 2003-January
      2005), only 35% of the 23 diagnosed cases showed extraocular spread (P = 0.002).
      More than one-third of patients in both time periods either refused therapy or
      abandoned treatment. CONCLUSION: This inexpensive approach is an effective first
      step toward improving survival of childhood retinoblastoma. Abandonment and
      refusal of therapy are continuing obstacles.

PMID- 17009237
TI  - Astrogliosis in EAE spinal cord: derivation from radial glia, and relationships
      to oligodendroglia.
AB  - A prominent feature of multiple sclerosis (MS) and experimental autoimmune
      encephalomyelitis (EAE) is the accumulation of enlarged, multipolar glial
      fibrillary acidic protein (GFAP) and brain lipid binding protein (BLBP)
      immunoreactive astroglia within and at the margins of the inflammatory
      demyelinative lesions. Whether this astrogliosis is due to both astroglial
      hyperplasia and hypertrophy or solely to astroglial hypertrophy is controversial.
      We now report that coincident with the first appearance of inflammation and
      clinical deficits in mice with myelin oligodendrocyte glycoprotein peptide (MOG
      peptide)-induced EAE, the radially oriented, bipolar, GFAP, and BLBP positive
      cells (adult radial glia) present in normal spinal cord white matter undergo
      mitosis and phenotypic transformation to hypertrophic astroglia. To facilitate
      visualization of relationships between these hypertrophic astroglia and dying and
      regenerating oligodendroglia, we used mice that express enhanced green
      fluorescent protein (EGFP) in cells of the oligodendroglial lineage. During the
      first week after onset of illness, markedly swollen EGFP+ cells without processes
      were seen within lesions, whereas EGFP+ cells that expressed immunoreactive
      cleaved caspase-3 were uncommon. These observations support the hypothesis that
      necrosis contributes to oligodendroglial loss early in the course of EAE. Later
      in the illness, EGFP+ cells accumulated amongst hypertrophic astroglia at the
      margins of the lesions, while the lesions themselves remained depleted of
      oligodendroglia, suggesting that migration of oligodendroglial lineage cells into
      the lesions was retarded by the intense perilesional gliosis.

PMID- 17009238
TI  - Heterogeneity of the coumarin anticoagulant targeted vitamin K epoxide reduction
      system. Study of kinetic parameters in susceptible and resistant mice (Mus
      musculus domesticus).
AB  - Vitamin K epoxide reductase (VKOR) activity in liver microsomes from a
      susceptible and a genetically warfarin-resistant strain of mice (Mus Musculus
      domesticus) was analyzed to determine the mechanism of resistance to this 4
      hydroxycoumarin derivative. Kinetic parameters for VKOR were calculated for each
      strain by incubating liver microsomes with vitamin K epoxide +/- warfarin. In
      susceptible mice, an Eadie-Hofstee plot of the data was not linear and suggested
      the involvement of at least two different components. Apparent kinetic parameters
      were obtained by nonlinear regression using a Michaelis--Menten model, which
      takes into account two enzymatic components. Component A presents a high Km and a
      high Vm, and as a consequence only an enzymatic efficiency Vm/Km was obtained
      (0.0024 mL/min/mg). Estimated warfarin Ki was 0.17 microM. Component B presented
      an apparent Km of 12.73 microM, an apparent Vm of 0.32 nmol/min/mg, and an
      apparent Ki for warfarin of 6.0 microM. In resistant mice, the enzymatic
      efficiency corresponding to component A was highly decreased (0.0003-0.00066
      mL/min/mg) while the Ki for warfarin was not modified. The apparent Vm of
      component B was poorly modified between susceptible and resistant mice. The
      apparent Km of component B observed in resistant mice was similar to the Km
      observed in susceptible mice. These modifications of the catalytic properties are
      associated with a single nucleotide polymorphism (T175G) in the VKOR-C1 gene,
      which corresponds to a Trp59Gly mutation in the protein.

PMID- 17009239
TI  - Osteoblastic response to collagen scaffolds varied in freezing temperature and
      glutaraldehyde crosslinking.
AB  - Collagen sponges are widely used scaffolds in bone engineering. To form bone, the
      osteoblastic cells undergo proliferation, differentiation, and mineralization
      stages in the scaffold. Crosslinking and freezing temperature are two important
      variables in fabricating collagen sponges. The purpose of this study was to
      examine the osteoblastic responses to collagen sponges prepared with or without
      glutaraldehyde crosslinking at different freezing temperatures (-20 degrees C or 
      80 degrees C). MC3T3-E1 osteoblastic cells were cultured in differently prepared
      sponges. Osteoblastic responses examined included cell numbers, osteocalcin
      expression, and calcium deposition. Cell numbers were measured by DNA content.
      Osteocalcin expression was determined by RT-PCR and real-time RT-PCR. Calcium
      deposition was assayed by ortho-cresophthalein complexone method and von Kossa
      stain. The osteoblastic cells grown in all collagen sponges did not show apparent
      signs of cytotoxicity. Collagen sponges differed in freezing temperatures
      resulted in similar osteoblastic responses. Glutaraldehyde-crosslinked sponges
      demonstrated less cell-mediated contraction and more cell numbers at day 7 (p <
      0.005). However, they showed lower osteocalcin expression at day 7 (p < 0.05) and
      less calcium deposition at day 21 (p < 0.001). In summary, different freezing
      temperatures played a minor role in osteoblastic responses. Glutaraldehyde
      crosslinking process, though improved the dimensional stability of collagen
      sponges, might compromise the osteoblastic differentiation and mineralization.

PMID- 17009240
TI  - Metabolic effects of carbenoxolone in rat liver.
AB  - The action of carbenoxolone on hepatic energy metabolism was investigated in the
      perfused rat liver and isolated mitochondria. In perfused livers, carbenoxolone
      (200-300 microM) increased oxygen consumption, glucose production and glycolysis
      from endogenous glycogen. Gluconeogenesis from lactate or fructose, an energy
      dependent process, was inhibited. This effect was already evident at a
      concentration of 25 microM. The cellular ATP levels and the adenine nucleotide
      content were decreased by carbenoxolone, whereas the AMP levels were increased.
      In isolated mitochondria, carbenoxolone stimulated state IV respiration and
      decreased the respiratory coefficient with the substrates beta-hydroxybutyrate
      and succinate. The ATPase of intact mitochondria was stimulated, the ATPase of
      uncoupled mitochondria was inhibited, and the ATPase of disrupted mitochondria
      was not altered by carbenoxolone. These results indicate that carbenoxolone acts
      as an uncoupler of oxidative phosphorylation and, possibly, as an inhibitor of
      the ATP/ADP exchange system. The inhibitory action of carbenoxolone on
      mitochondrial energy metabolism could be contributing to induce the mitochondrial
      permeability transition (MPT), a key phenomenon in apoptosis. The results of the
      present study can explain, partly at least, the in vivo hepatotoxic actions of
      carbenoxolone that were found in a previous clinical evaluation.

PMID- 17009241
TI  - The -786C/T single-nucleotide polymorphism in the promoter of the gene for
      endothelial nitric oxide synthase: insensitivity to physiologic stimuli as a risk
      factor for rheumatoid arthritis.
AB  - OBJECTIVE: Shear stress is the main physiologic stimulus for the expression of
      NOS3, the gene for human endothelial nitric oxide synthase. Interestingly, a
      promoter variant of the NOS3 gene, the -786C variant, is insensitive to shear
      stress, and individuals homozygous for this single-nucleotide polymorphism (SNP)
      have an increased risk of developing coronary artery disease. The cytokine
      interleukin-10 (IL-10) is also capable of up-regulating endothelial NOS3
      expression through binding of the transcription factor STAT-3 to a nearby
      promoter sequence. The aim of this study was to explore the possibility that the 
      786C variant of the NOS3 gene is also insensitive to IL-10 and that individuals
      with the -786C/C genotype are more prone to developing rheumatoid arthritis (RA).
      METHODS: Endothelial cells were isolated from human umbilical cord veins,
      clonally expanded, and analyzed for NOS3 and IL-12 expression by real-time
      quantitative reverse transcription-polymerase chain reaction and enzyme-linked
      immunosorbent assay. Umbilical cord arteries and blood samples from RA patients
      were genotyped for the -786C/T SNP of the NOS3gene. RESULTS: In contrast to cells
      of other genotypes, endothelial cells of the -786C/C genotype did not reveal an
      increase in NOS3 expression upon exposure to IL-10, and the cytokine failed to
      suppress IL-12 expression upon stimulation of CD40. Preincubation of these cells
      with a 16-mer C-type decoy oligonucleotide fully reconstituted the defective IL
      10-induced suppression of IL-12 synthesis. The frequency of the -786C/C genotype
      was significantly higher in the 596 RA patients than in the general population
      (19.1% versus 12.1%; P < 0.0001). CONCLUSION: Individuals with the -786C/C
      genotype have an increased risk of developing RA. This may be explained by the IL
      10 insensitivity of the C-type NOS3 gene promoter and the resulting failure to
      subdue CD40-mediated proinflammatory gene expression.

PMID- 17009242
TI  - Pannexin1 is expressed by neurons and glia but does not form functional gap
      junctions.
AB  - Pannexins are a newly described family of proteins that may form gap junctions.
      We made antisera against mouse pannexin1 (Panx1). HeLa cells expressing Panx1
      have cell surface labeling, but not gap junction plaques, and do not transfer
      small fluorescent dyes or neurobiotin in a scrape-loading assay. Neuro2a cells
      expressing Panx1 are not electrophysiologically coupled. Intracellular Panx1
      immunoreactivity, but not gap junction plaques, is seen in cultured
      oligodendrocytes, astrocytes, and hippocampal neurons. Thus, at least in these
      mammalian cells lines, Panx1 does not form morphological or functional gap
      junctions, and it remains to be demonstrated that Panx1 forms gap junction
      forming protein in the CNS.

PMID- 17009243
TI  - Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid
      arthritis synovial tissue and human cartilage cocultures.
AB  - OBJECTIVE: To investigate the role of oncostatin M (OSM) in cell adhesion,
      angiogenesis, and matrix degradation in rheumatoid arthritis (RA) synovial tissue
      and normal human cartilage. METHODS: Human dermal microvascular endothelial cell
      (HDMEC) and RA synovial fibroblast (RASF) proliferation and intercellular
      adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)
      expression were assessed by a bromodeoxyuridine proliferation assay and flow
      cytometry. HDMEC tubule formation and migration were assessed by Matrigel culture
      and migration assay. Production of matrix metalloproteinase (MMP) and tissue
      inhibitor of metalloproteinases 1 (TIMP-1) in RA synovial explants, and
      proteoglycan/glycosaminoglycan (GAG) release, vascular endothelial growth factor
      (VEGF), and angiopoietin 2 production from RASF/normal cartilage cocultures were
      assessed by enzyme-linked immunosorbent assay and immunohistology. RESULTS:
      HDMEC/RASF proliferation was induced by OSM and interleukin-1beta (IL-1beta),
      alone and in combination. OSM enhanced cell surface expression of ICAM-1, but not
      VCAM-1, on endothelial cells and RASFs. OSM increased endothelial cell tubule
      formation and migration. In RA synovial explants, OSM induced production of MMP-1
      and TIMP-1. When OSM was combined with IL-1beta, however, the MMP-1:TIMP-1 ratio
      was significantly increased. OSM potentiated IL-1beta-induced MMP-1 and MMP-13
      expression in normal human cartilage/RASF cocultures, resulting in a significant
      increase in the MMP:TIMP ratio. In OSM/IL-1beta- stimulated cocultures, cartilage
      sections demonstrated significant proteoglycan depletion that was paralleled by a
      significant increase in GAG release in supernatants. Finally, compared with
      either cytokine alone, the combination of OSM and IL-1beta significantly induced
      VEGF production in RASF/cartilage cocultures. CONCLUSION: These data suggest that
      OSM promotes angiogenesis and endothelial cell migration and potentiates the
      effects of IL-1beta in promoting extracellular matrix turnover and human
      cartilage degradation. Furthermore, the induction of VEGF in cocultures supports
      the hypothesis of a link between angiogenesis and cartilage degradation.

PMID- 17009244
TI  - IKKbeta inhibition protects against bone and cartilage destruction in a rat model
      of rheumatoid arthritis.
AB  - OBJECTIVE: The IKK complex regulates NF-kappaB activation, an important pathway
      implicated in the rheumatoid arthritis (RA) disease process. This study was
      undertaken to assess the efficacy of N-(6-chloro-7-methoxy-9H-beta-carbolin-8-yl)
      2-methylnicotinamide (ML120B), a potent and selective small molecule inhibitor of
      IKKbeta. METHODS: Polyarthritis was induced in rats by injection of Freund's
      complete adjuvant into the hind footpad. ML120B was administered orally twice
      daily, either prophylactically or therapeutically. Paw volumes and body weights
      were measured every 2-3 days throughout the study. We assessed bone erosions by
      several methods: histologic evaluation, quantitative micro-computed tomography
      (micro-CT) imaging analysis, and measurement of type I collagen fragments in the
      serum. Quantitative polymerase chain reaction was used to evaluate expression of
      messenger RNA for genes related to inflammation and to bone and cartilage
      integrity. RESULTS: Oral administration of ML120B inhibited paw swelling in a
      dose-dependent manner (median effective dosage 12 mg/kg twice daily) and offered
      significant protection against arthritis-induced weight loss as well as cartilage
      and bone erosion. We were able to directly demonstrate that NF-kappaB activity in
      arthritic joints was reduced after ML120B administration. Also, we observed that
      down-regulation of the NF-kappaB pathway via IKKbeta inhibition dampened the
      chronic inflammatory process associated with rat adjuvant-induced arthritis.
      CONCLUSION: The results of the present study suggest that IKKbeta inhibition is
      an effective therapeutic approach to treat both the inflammation and the
      bone/cartilage destruction observed in RA. Methods for the determination of serum
      markers for bone and cartilage destruction, as well as micro-CT analysis, may aid
      in predicting and evaluating the therapeutic efficacy of IKKbeta inhibition
      therapy in humans.

PMID- 17009245
TI  - Effect of octanol:water partition coefficients of organophosphorus compounds on
      biodistribution and percutaneous toxicity.
AB  - Knowledge of partition coefficient (log P) data can play a critical role in
      understanding the pharmacokinetic and pharmacodistributive properties of toxic
      organophosphorus (OP) compounds. Using a recently published gas chromatographic
      method, the octanol:water log P values for the compounds tabun (GA), sarin (GB),
      cyclosarin (GF), and O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate
      (VX) were determined to be 0.384 +/- 0.033, 0.299 +/- 0.016, 1.038 +/- 0.055, and
      0.675 +/- 0.070, respectively. Based on these data, the log P value of the
      fluorophosphonate fragment, common to GB, soman (GD), and GF, was determined to
      be -2.256 +/- 0.273. The predictive value for absorption and distribution of the
      determined log P values was compared to measured values. The time to onset of
      local fasciculations (47.3, 29.0, 8.8, 8.5, and 6.3 min, respectively) in guinea
      pigs exposed percutaneously to equilethal doses of GA, VX, GF, GB, or GD was used
      as an indicator of dermal penetration. There was a good correlation (r = 0.95)
      between the measured log P value and the rate of onset of local fasciculations.
      Assuming a direct correspondence, equilibrium tissue:blood log P may be estimated
      from octanol:water log P. Comparison of the estimated and directly measured
      tissue:blood log P revealed a correlation of 0.8 for GD in liver, muscle, and
      adipose tissue. Our results demonstrate the use of log P data to both predict
      absorption and determine the distribution of OP compounds in tissues. This
      facilitates further estimates of in vivo OP effects from in vitro experiments.

PMID- 17009246
TI  - Influence of ethanol on methanol-induced oxidative stress and neurobehavioral
      deficits.
AB  - The present study examines the efficacy of ethanol as an antidote in methanol
      neurotoxicity in terms of its effect on antioxidant defense system and behavior.
      It was observed that acute methanol exposure (7.5 g/kg body weight) led to an
      increase in lipid peroxidation in various regions of brain. Ethanol
      administration (7.5 g/kg body weight), on the other hand, was found to accentuate
      methanol-induced lipid peroxidation. Glutathione levels in brain were
      significantly reduced in methanol-exposed animals. However, in the coexposed
      animals, the levels of glutathione were comparable to those observed in controls.
      The activities of superoxide dismutase and catalase were decreased in the brain
      following methanol exposure, whereas in methanol- and ethanol-coexposed animals
      there was no significant effect on these enzymes as compared to methanol-exposed
      animals. The activity of acetylcholinesterase was significantly reduced in the
      methanol-exposed animals. On the other hand, acetylcholinesterase activity was
      not affected in the coexposed animals in comparison to methanol-treated group.
      Neurobehavioral studies revealed impaired motor and cognitive functions following
      methanol exposure. In contrast, ethanol exposure ameliorated the behavioral
      deficits induced by methanol. The findings from the present study suggest the
      beneficial effect of ethanol on neurobehavioral deficits induced by methanol
      along with intensification of methanol-induced oxidative stress.

PMID- 17009247
TI  - Regulation of Mcl-1 expression in rheumatoid arthritis synovial macrophages.
AB  - OBJECTIVE: Resistance to apoptosis may be an important mechanism contributing to
      the persistence of rheumatoid arthritis (RA). This study was undertaken to
      characterize the expression, regulation, and function of the antiapoptotic Bcl-2
      family member Mcl-1 in macrophages isolated from the joints of patients with RA.
      METHODS: Mononuclear cells were isolated from the synovial fluid (SF) of patients
      with RA. Mcl-1 expression was documented by intracellular staining of CD14+ cells
      using flow cytometry, and by real-time polymerase chain reaction or immunoblot
      analysis of isolated macrophages. The expression of Mcl-1 was suppressed with
      small interfering RNA (siRNA) or chemical inhibitors of the phosphatidylinositol
      3-kinase (PI 3-kinase)/Akt-1 and signal transducer and activator of transcription
      3 (STAT-3) pathways. Apoptosis was defined by the loss of mitochondrial
      transmembrane potential and by DNA fragmentation. RESULTS: The expression of Mcl
      1 was increased in CD14+ macrophages from the SF of patients with RA compared
      with normal in vitro-differentiated macrophages. Inhibition of the PI 3
      kinase/Akt-1 or STAT-3 pathways significantly reduced the percentage of CD14+
      cells within the SF and resulted in the reduction of Mcl-1 and the induction of
      apoptosis of synovial macrophages. Transfection of RA synovial macrophages with
      Mcl-1 siRNA resulted in apoptotic cell death. CONCLUSION: Mcl-1 is critical for
      the survival of macrophages in the joints of patients with RA, and is therefore a
      potential therapeutic target in this disease.

PMID- 17009248
TI  - Bim deficiency leads to exacerbation and prolongation of joint inflammation in
      experimental arthritis.
AB  - OBJECTIVE: : Rheumatoid arthritis (RA) is characterized by hyperplasia of the
      synovial lining, inflammation, and destruction of cartilage and bone. Since there
      are only a few detectable cells undergoing apoptosis in the joint, it is possible
      that a defect in apoptosis may contribute to synovial hyperplasia. This study
      sought to identify and characterize the direct role of apoptotic regulators in a
      mouse model of inflammatory arthritis. METHODS: Using a serum transfer model,
      experimental arthritis was induced in mice lacking the proapoptotic Bcl-2 family
      genes Bak (Bak-/-), Bax (Bax-/-), or Bim (Bim-/-), as compared with wild-type
      (WT) control mice. Physical examination for edema of the ankles and
      histopathologic analysis of ankle sections were used to determine the severity of
      arthritis. The serum and ankles were examined for production of chemokines and
      cytokines using enzyme-linked immunosorbent or Luminex-based assays. RESULTS: Bim
      /- mice displayed increased severity and prolongation of arthritis. In contrast,
      Bak-/- and Bax-/- mice showed no difference in the severity of arthritis as
      compared with WT mice. In addition, Bim-/- mice had elevated levels of
      proinflammatory chemokines and cytokines, decreased joint and serum production of
      antiinflammatory cytokines, fewer TUNEL-positive cells, and reduced levels of
      active caspase 3 as compared with WT mice. CONCLUSION: These studies are the
      first to demonstrate a role for the proapoptotic Bcl-2 protein Bim in the
      effector phase of RA. The findings indicate that Bim potentially functions to
      repress the effector phase of arthritis by regulating the milieu of the joint and
      serum, and by inducing apoptosis.

PMID- 17009249
TI  - Cytokine production following experimental implantation of xenogenic dermal
      collagen and polypropylene grafts in mice.
AB  - AIM: We earlier showed that xenogenic Pelvicol (Bard, Olen, Belgium) implants
      induce a lesser inflammatory response than Prolene (Johnson and Johnson, Dilbeek,
      Belgium). The purpose of this study was to determine cytokine profiles in the
      host immune responses to Pelvicol in a mouse model. The hypothesis was that
      Pelvicol would induce a "T-helper2" (Th2) rather than T-helper1 (Th1) type of
      inflammatory response. METHODS: Mice were implanted subcutaneously with Pelvicol
      or Prolene and the graft sites were harvested at 3 to 28 days. Histopathology was
      done and cytokine levels were determined by immunohistochemistry and RT-PCR. Flow
      cytometry was used to identify which cell population contributed to the observed
      cytokine production profiles. RESULTS: Pelvicol induced a decreased inflammation
      and displayed an increase in IL-10 and TGF-beta, but reduce of TNF-alpha and IFN
      gamma, indicating a Th2 type dominated response as examined by
      immunohistochemistry and RT-PCR. Flow cytometry showed that the
      monocytes/maceophages were the main cell population responsible for production of
      these cytokines. Monocytes/maceophages from Pelvicol explants showed upregulated
      expression of IL-10 while Prolene explants expressed TNF-alpha. CONCLUSION:
      Pelvicol induced a Th2 type cytokine-dominated immune response after subcutaneous
      implantation in mice.

PMID- 17009250
TI  - Influence of copper on the interaction between cytochrome c and sulfite in vitro.
AB  - The quantitative influence of copper on the interaction between cytochrome c and
      sulfite, which is a derivate of sulfur dioxide in the human body, has been
      studied by fluorescence spectrometry and ultraviolet absorption spectrometry in
      vitro. The results indicate that copper may intensely combine with protein
      component and ferroporphyrin component in cytochrome c at the concentration of
      0.1 mM, and the respective association constants (K(A)) are 3.77 x 10(4) L mol(
      1) and 9.38 x 10(3) L mol(-1). Sulfite has little interaction with the protein
      component in cytochrome c (K(A) = 0.094 L mol(-1)), at either low concentrations
      or relatively high concentrations (<0.15 M). However, it can react with the
      ferroporphyrin component in cytochrome c (K(A) = 4.297 L mol(-1)). After copper
      is added to the sulfite-cytochrome c binary systems, the reaction between sulfite
      and the protein component in cytochrome c is obviously strengthened at a low
      concentration (K(A) = 7.289 L mol(-1)), while the addition of copper merely has a
      little effect on the interaction between sulfite and the ferroporphyrin component
      in cytochrome c.

PMID- 17009251
TI  - Effect of hormone therapy on risk of hip and knee joint replacement in the
      Women's Health Initiative.
AB  - OBJECTIVE: To determine the effect of hormone therapy on arthroplasty rates.
      METHODS: We examined data from the Women's Health Initiative placebo-controlled,
      double-blind, randomized trials. Community-dwelling women ages 50-79 years were
      enrolled at 40 US clinics. Women with prior arthroplasty were excluded, yielding
      a sample size of 26,321 subjects. Women who had had hysterectomies (n = 10,272)
      were randomly assigned to receive 0.625 mg/day conjugated equine estrogens (n =
      5,076), or placebo (n = 5,196), with a mean followup of 7.1 years. Those who had
      not had hysterectomies (n = 16,049) were randomly assigned to receive estrogen
      plus progestin (n = 8,240), given as 0.625 mg/day conjugated equine estrogens
      plus 2.5 mg/day medroxyprogesterone acetate, or placebo (n = 7,809), with a mean
      followup of 5.6 years. Participants reported hospitalizations, and arthroplasties
      were identified by procedure codes. Arthroplasties due to hip fracture were
      censored. Cox proportional hazards regression was used to assess hazard ratios
      (HRs) and 95% confidence intervals (95% CIs) using intent-to-treat methods and
      outcome of time to first procedure. RESULTS: In the estrogen-alone trial, women
      receiving hormone therapy had significantly lower rates of any arthroplasty (HR
      0.84 [95% CI 0.70-1.00], P = 0.05). However, this effect was borderline
      statistically significant for hip arthroplasty (HR 0.73 [95% CI 0.52-1.03], P =
      0.07), and not significant for knee arthroplasty (HR 0.87 [95% CI 0.71-1.07], P =
      0.19). In the estrogen-plus-progestin trial, there was no association for total
      arthroplasty (HR 0.99 [95% CI 0.82-1.20], P = 0.92) or for individual hip (HR
      1.14 [95% CI 0.83-1.57], P = 0.41) or knee (HR 0.91 [95% CI 0.72-1.15], P = 0.41)
      arthroplasties. CONCLUSION: These data suggest that hormone therapy may influence
      joint health, but this observed decrease in risk may be limited to unopposed
      estrogen and may possibly be more important in hip than in knee osteoarthritis.

PMID- 17009252
TI  - In patients undergoing neuromodulation for intractable urge incontinence a
      reduction in 24-hr pad weight after the initial test stimulation best predicts
      long-term patient satisfaction.
AB  - AIMS: To evaluate long-term patient satisfaction of sacral neuromodulation and to
      correlate satisfaction with incontinence parameters. METHODS: Patients at least 1
      year remote from sacral neuromodulation were mailed a questionnaire to evaluate
      satisfaction and assess incontinence symptoms. RESULTS: Fifty-two patients were
      consecutively enrolled in the study. Forty-nine questionnaires (94.2%) were
      returned. The average interval between implantation and questionnaire completion
      was 27.2 (range 12-52) months. 83.7% of respondents were satisfied and 79.6% of
      patients would "do it all over again." Compared to dissatisfied subjects during
      test stimulation, the satisfied patients had a significant decrease in 24-hr pad
      weight (84.5% vs. 60.6%, P = 0.002) but did not differ in daily pad usage (4.5
      fewer pads per day vs. 3.4, P = 0.190). At long-term follow-up, satisfied
      patients noted significantly greater improvement in their Incontinence Impact
      Questionnaire score versus dissatisfied patients (mean improvement 53 vs. 10
      points, P = 0.0003). Using multiple logistic regression, change in 24-hr pad
      weight, but not change in average daily pad usage, was correlated with long-term
      satisfaction. CONCLUSIONS: Eighty-four percent of patients were satisfied with
      sacral neuromodulation at a mean of 27 months. An 84.5% reduction in 24-hr pad
      weight correlated with long-term patient satisfaction. In addition to lack of
      efficacy, device pain was a contributing factor to dissatisfaction.

PMID- 17009253
TI  - Oral salmon calcitonin reduces Lequesne's algofunctional index scores and
      decreases urinary and serum levels of biomarkers of joint metabolism in knee
      osteoarthritis.
AB  - OBJECTIVE: To evaluate the effects of oral salmon calcitonin (sCT) on Lequesne's
      algofunctional index scores and on biomarkers of joint metabolism in knee
      osteoarthritis. METHODS: In this randomized, double-blind trial, patients
      received either placebo (n = 18), 0.5 mg of sCT (n = 17), or 1 mg of sCT (n = 18)
      daily for 84 days. Biomarkers included C-telopeptide of type II collagen (CTX
      II), type II collagen neoepitope C2C, collagenases (matrix metalloproteinase 1
      [MMP-1], MMP-8, and MMP-13), stromelysin (MMP-3), tissue inhibitors of
      metalloproteinases 1 and 2, and hyaluronan. Statistical analysis included
      nonparametric tests. RESULTS: A total of 41 patients completed the study (13 in
      the group receiving 0.5 mg of sCT and 14 in each of the other 2 other groups).
      Although, on day 84, patients in both the placebo group and the group receiving 1
      mg of sCT exhibited a similar significant decrease in pain scores, a significant
      reduction in the function score was observed only in the 2 sCT groups. On day 84,
      there was no significant decrease in biomarker levels in the placebo group,
      whereas significant reductions in the levels of both MMP-3 and hyaluronan were
      observed in the 2 sCT groups. The group of patients receiving 1 mg of sCT
      exhibited significant decreases in the levels of CTX-II, C2C, and MMP-13.
      CONCLUSION: By improving functional disability and by reducing levels of
      biomarkers that are thought to be predictive of joint space narrowing (and thus
      cartilage loss), oral sCT at a dose of 1 mg might be a useful pharmacologic agent
      in human knee OA.

PMID- 17009254
TI  - Correlation between motor function and lower urinary tract dysfunction in
      patients with infantile cerebral palsy.
AB  - AIMS: The aim of this study was to evaluate urodynamic findings in patients with
      infantile cerebral palsy (CP) and to correlate the findings with impaired motor
      function. METHODS: We conducted a videourodynamic investigation on a highly
      select group of 29 patients (3-53 years). Motor function was assessed in each
      patient by the Gross Motor Function Classification System for CP (GMFCS). With
      this system, motor function is divided into five levels: patients in Level I have
      the most independent motor function and patients in Level V the least. The
      patients were divided into Group 1 (23 symptomatic patients with recurrent
      urinary tract infection or urinary incontinence) and Group 2 (6 asymptomatic
      patients). RESULTS: In Group 1, 21 patients (91%) had reduced compliance (0.6
      16.4 ml/cmH(2)O) and 16 patients (70%) had increased DLPP (>40 cmH(2)O). Detrusor
      overactivity and pelvic floor overactivity were found in all 23 patients. In
      Group 2, two patients (33%) had reduced compliance (0.7 and 5.8 ml/cmH(2)O) and
      four (67%) had increased DLPP (>40 cm H(2)O). Detrusor overactivity and pelvic
      floor overactivity were observed in five patients (83%). Symptomatic patients
      showed higher GMFCS levels than asymptomatic patients. In the group of
      asymptomatic patients, there was no one classified as Levels IV or V, while there
      were no symptomatic patients classified as Level I. CONCLUSIONS: We conclude that
      urinary symptoms and pathological urodynamic findings increase along with the
      degree of motor function impairment shown by the GMFCS. Pathologic urodynamic
      findings can be found in both symptomatic and in asymptomatic patients.

PMID- 17009255
TI  - A prospective population-based study of the predictors of undergoing total joint
      arthroplasty.
AB  - OBJECTIVE: To examine prospectively the predictors of time to total joint
      arthroplasty (TJA). METHODS: This was a prospective cohort study with a median
      followup time of 6.1 years. We included participants from an existing population
      based cohort of 2,128 individuals, ages 55 years and older with disabling hip
      and/or knee arthritis and no prior TJA, from 2 regions of Ontario, Canada, 1
      urban with low TJA rates and 1 rural with high rates. The main outcome measure
      was the occurrence of a TJA based on procedure codes in the hospital discharge
      abstract database. RESULTS: At baseline, the mean age of the patients was 71.5
      years, 67.9% had a high school education or higher, 73.4% were women, the mean
      arthritis severity (Western Ontario and McMaster Universities Osteoarthritis
      Index [WOMAC]) score was 41.1 (maximum possible score 100), and 20.0% were
      willing to consider TJA. Greater probability of undergoing TJA was associated
      with higher (worse) baseline WOMAC scores (hazard ratio [HR] 1.22 per 10-unit
      increase, P < 0.001), age (compared with age <or=62 years, the HR increased to
      1.57 for 63-68 years, 1.46 for 69-74 years, and 1.51 for 75-81 years, and fell to
      0.44 for >or=82 years; P < 0.05 for all), better health (HR 1.14 per 10-unit
      increase in Short Form 36 general health survey score, P < 0.001), and
      willingness to consider TJA (HR 4.92, P < 0.001). When willingness was excluded
      from the model, education level, but not sex or income, became a significant
      predictor of TJA receipt. CONCLUSION: Willingness to consider TJA was the
      strongest predictor of the time to first TJA. Given that previous research
      indicates that willingness is largely explained by perceptions of the indications
      for and risks associated with TJA and not disease severity, this finding supports
      the need for population education about arthritis treatments, including TJA.

PMID- 17009256
TI  - Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats.
AB  - Hyperglycemia of diabetes has been implicated in increased tissue oxidative
      stress, with consequent development of secondary complications. Thus, stabilizing
      glucose levels near normal levels is of utmost importance. Because diet
      influences glycemic control, this study investigated whether a low-carbohydrate
      (5.5%) diet confers beneficial effects on the oxidative status of the heart,
      kidney, and liver in diabetes. Male and female normal and diabetic rats were fed
      standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated
      glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals
      were reduced or normalized by the low-carbohydrate diet. While diabetes increased
      cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet
      normalized cardiac glutathione peroxidase activity in diabetic animals, and
      reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had
      altered activities of renal glutathione reductase and superoxide dismutase, but
      increased renal glutathione peroxidase activity in diabetic animals was not
      corrected by the test diet. In the liver, diabetes was associated with a decrease
      in catalase activity and glutathione levels and an increase in glutathione
      peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic
      glutathione peroxidase activity and lipid peroxidation were noted in diet-treated
      diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia
      and did not produce overtly negative effects in tissues of normal or diabetic
      rats.

PMID- 17009257
TI  - The role of fibroblasts and fibroblast-derived factors in periprosthetic
      osteolysis.
AB  - OBJECTIVE: This study was undertaken to investigate how fibroblasts respond to
      stimulation with particulate wear debris and/or conditioned media obtained from
      pathologic tissue, and whether these activated fibroblasts express compounds that
      are involved in bone resorption. METHODS: Conditioned media from explant cultures
      of synovial tissue, periprosthetic soft tissue (interface membranes), titanium
      particles, and proinflammatory cytokines were used to stimulate fibroblasts.
      RNase protection assay was used to measure altered gene expression, and enzyme
      linked immunosorbent assay, Western blot hybridization, and flow cytometry were
      used to determine fibroblast protein expression. Tartrate-resistant acid
      phosphatase staining was used to identify multinucleated osteoclast-like cells.
      RESULTS: The most dominant compounds measured in the conditioned media from
      interface membranes were tumor necrosis factor alpha (TNFalpha), monocyte
      chemoattractant protein 1 (MCP-1), interleukin-1beta (IL-1beta), IL-6, IL-8, and
      vascular endothelial growth factor. Fibroblasts phagocytosed particulate wear
      debris and responded to cytokine/chemokine stimulation. The most prominent up
      regulated genes and proteins secreted by fibroblasts in response to stimulation
      were matrix metalloproteinase 1, MCP-1, IL-1beta, IL-6, IL-8, cyclooxygenase 1
      (COX-1), COX-2, leukemia inhibitory factor 1, transforming growth factor beta1
      (TGFbeta1), and TGFbeta receptor type I. In addition, interface membrane
      fibroblasts expressed RANKL and osteoprotegerin in response to stimulation with
      conditioned media, TNFalpha, or IL-1beta. Stimulated fibroblasts cocultured with
      bone marrow cells in the presence of macrophage colony-stimulating factor induced
      osteoclastogenesis. CONCLUSION: Interface membrane fibroblasts respond directly
      to particulate wear debris, possibly via phagocytosis, expressing proinflammatory
      cytokines and RANKL. Thus, these cells may be actively involved in
      osteoclastogenesis and pathologic (periprosthetic) bone resorption.

PMID- 17009258
TI  - Tetraspanin CD151 is expressed in osteoarthritic cartilage and is involved in
      pericellular activation of pro-matrix metalloproteinase 7 in osteoarthritic
      chondrocytes.
AB  - OBJECTIVE: The proenzyme of matrix metalloproteinase 7 (proMMP-7), which can
      degrade various extracellular matrix (ECM) and non-ECM molecules after being
      activated, is overexpressed in osteoarthritic (OA) articular cartilage, but the
      process of its activation in the cartilage remains unknown. The present study was
      undertaken to investigate the expression of tetraspanin CD151 in OA cartilage and
      its involvement in proMMP-7 activation. METHODS: The expression of CD151 in
      articular cartilage was examined by reverse transcription-polymerase chain
      reaction (RT-PCR), real-time PCR, immunohistochemistry, in situ hybridization,
      and immunoblotting. Chondrocytes were used to study the interaction between CD151
      and proMMP-7, and activation of proMMP-7. RESULTS: RT-PCR revealed expression of
      CD151 messenger RNA in all OA cartilage samples, but in only 30% of normal
      control cartilage samples. Immunohistochemistry and in situ hybridization
      findings indicated that CD151 was coexpressed with proMMP-7 in chondrocytes,
      mainly in the superficial and transitional zones of OA cartilage. CD151
      immunoreactivity directly correlated with the Mankin score (r = 0.757, P < 0.0001
      [n = 30]) and the degree of chondrocyte cloning (r = 0.83, P < 0.0001 [n = 30])
      in the cartilage samples. Complexes CD151 and proMMP-7 and their colocalization
      on the cell membranes were demonstrated by immunoprecipitation and double
      fluorescence immunostaining of the OA chondrocytes. In situ zymography indicated
      that chondrocytes exhibit pericellular proteolytic activity, which was abolished
      by treatment with MMP inhibitors, anti-MMP-7 antibody, or anti-CD151 antibody.
      CONCLUSION: These data demonstrate that CD151 is overexpressed in OA cartilage
      and suggest that CD151 plays a role in the pericellular activation of proMMP-7,
      leading to cartilage destruction and/or chondrocyte cloning.

PMID- 17009259
TI  - Matrix metalloproteinase 10 promotion of collagenolysis via procollagenase
      activation: implications for cartilage degradation in arthritis.
AB  - OBJECTIVE: We have previously reported the up-regulation of matrix
      metalloproteinase 10 (MMP-10) following treatment with the procatabolic stimulus
      of interleukin-1 (IL-1) and oncostatin M (OSM) in chondrocytes. Although MMP-10
      is closely related to MMP-3, little is known about the role of MMP-10 in
      cartilage catabolism. The purpose of this study was to determine whether MMP-10
      is expressed in connective tissue cells and to assess how it may contribute to
      cartilage collagenolysis. METHODS: MMP gene expression was assessed by real-time
      polymerase chain reaction using RNA from human articular chondrocytes and
      synovial fibroblasts stimulated with IL-1 plus OSM or tumor necrosis factor alpha
      (TNFalpha) plus OSM. Synovial fluid levels of MMP-10 were determined by specific
      immunoassay. Recombinant procollagenases were used in activation studies.
      Immunohistochemistry assessed MMP-10 expression in diseased joint tissues.
      RESULTS: MMP-10 expression was confirmed in both chondrocytes and synovial
      fibroblasts following stimulation with either IL-1 plus OSM or TNFalpha plus OSM,
      and MMP-10 was detected in synovial fluid samples from patients with various
      arthropathies. Exogenous MMP-10 significantly enhanced collagenolysis from IL-1
      plus OSM-stimulated cartilage, and MMP-10 activated proMMP-1, proMMP-8, and
      proMMP-13. Immunohistochemistry revealed the presence of MMP-10 in the synovium
      and cartilage of an IL-1 plus OSM-induced model of arthritis as well as in
      samples of diseased human tissues. CONCLUSION: We confirm that both synovial
      fibroblasts and articular chondrocytes express MMP-10 following treatment with
      procatabolic stimuli. Furthermore, the detectable levels of synovial fluid MMP-10
      and the histologic detection of this proteinase in diseased joint tissues
      strongly implicate MMP-10 in the cartilage degradome during arthritis. The
      ability of MMP-10 to superactivate procollagenases that are relevant to cartilage
      degradation suggests that this activation represents an important mechanism by
      which this MMP contributes to tissue destruction in arthritis.

PMID- 17009261
TI  - Interleukin-1alpha induction of tensile weakening associated with collagen
      degradation in bovine articular cartilage.
AB  - OBJECTIVE: To determine whether interleukin-1alpha (IL-1alpha) induces tensile
      weakening of articular cartilage that is concomitant with the loss of
      glycosaminoglycans (GAGs) or the subsequent degradation of the collagen network.
      METHODS: Explants of young adult bovine cartilage obtained from the superficial
      (including the articular surface), middle, and deep layers were cultured with or
      without IL-1alpha for 1 week or 3 weeks. Then, portions of the explants were
      analyzed for their tensile properties (ramp modulus, strength, and failure
      strain); other portions of explants and spent culture medium were analyzed for
      the amount of GAG and the amount of cleaved, denatured, and total collagen.
      RESULTS: The effect of IL-1alpha treatment on cartilage tensile properties and
      content was dependent on the duration of culture and the depth of the explant
      from the articular surface. The tensile strength and failure strain of IL-1alpha
      treated samples from the superficial and middle layers were lower after 3 weeks
      of culture, but not after 1 week of culture. However, by 1 week of culture, IL
      1alpha had already induced release of the majority of tissue GAGs into the
      medium, without detectable loss or degradation of collagen. In contrast, after 3
      weeks of culture, IL-1alpha induced significant collagen degradation, as
      indicated by the amount of total, cleaved, or denatured collagen in the medium or
      in explants from the superficial and middle layers. CONCLUSION: IL-1alpha-induced
      degradation of cartilage results in tensile weakening that occurs subsequent to
      the depletion of GAG and concomitant with the degradation of the collagen
      network.

PMID- 17009260
TI  - Premature induction of hypertrophy during in vitro chondrogenesis of human
      mesenchymal stem cells correlates with calcification and vascular invasion after
      ectopic transplantation in SCID mice.
AB  - OBJECTIVE: Functional suitability and phenotypic stability of ectopic transplants
      are crucial factors in the clinical application of mesenchymal stem cells (MSCs)
      for articular cartilage repair, and might require a stringent control of
      chondrogenic differentiation. This study evaluated whether human bone marrow
      derived MSCs adopt natural differentiation stages during induction of
      chondrogenesis in vitro, and whether they can form ectopic stable cartilage that
      is resistant to vascular invasion and calcification in vivo. METHODS: During in
      vitro chondrogenesis of MSCs, the expression of 44 cartilage-, stem cell-, and
      bone-related genes and the deposition of aggrecan and types II and X collagen
      were determined. Similarly treated, expanded articular chondrocytes served as
      controls. MSC pellets were allowed to differentiate in chondrogenic medium for 3
      7 weeks, after which the chondrocytes were implanted subcutaneously into SCID
      mice; after 4 weeks in vivo, samples were evaluated by histology. RESULTS: The 3
      stage chondrogenic differentiation cascade initiated in MSCs was primarily
      characterized by sequential up-regulation of common cartilage genes. Premature
      induction of hypertrophy-related molecules (type X collagen and matrix
      metalloproteinase 13) occurred before production of type II collagen and was
      followed by up-regulation of alkaline phosphatase activity. In contrast,
      hypertrophy-associated genes were not induced in chondrocyte controls. Whereas
      control chondrocyte pellets resisted calcification and vascular invasion in vivo,
      most MSC pellets mineralized, in spite of persisting proteoglycan and type II
      collagen content. CONCLUSION: An unnatural pathway of differentiation to
      chondrocyte-like cells was induced in MSCs by common in vitro protocols. MSC
      pellets transplanted to ectopic sites in SCID mice underwent alterations related
      to endochondral ossification rather than adopting a stable chondrogenic
      phenotype. Further studies are needed to evaluate whether a more stringent
      control of MSC differentiation to chondrocytes can be achieved during cartilage
      repair in a natural joint environment.

PMID- 17009263
TI  - Low blood concentration of hydroxychloroquine is a marker for and predictor of
      disease exacerbations in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To study the possible relationship between whole-blood
      hydroxychloroquine (HCQ) concentrations and clinical efficacy of HCQ in patients
      with systemic lupus erythematosus (SLE). METHODS: Whole-blood HCQ concentrations
      were measured, under blinded conditions, in 143 unselected patients with SLE who
      had been receiving HCQ 400 mg daily for at least 6 months. The relationship of
      these concentrations to current disease activity and to subsequent exacerbations
      during 6 months of followup was investigated. RESULTS: At baseline, 23 patients
      had active disease (mean +/- SD SLE Disease Activity Index 12.4 +/- 7.5). The
      mean whole-blood HCQ concentration in this group was significantly lower than
      that in the 120 patients with inactive disease (694 +/- 448 ng/ml versus 1,079 +/
      526 ng/ml; P = 0.001). Among the 120 patients who had inactive disease at
      baseline, the mean HCQ concentration at baseline in the 14 (12%) who had disease
      exacerbations during followup was significantly lower than that in the patients
      whose disease remained inactive. Multivariate logistic regression showed that the
      HCQ concentration was the only predictor of exacerbation (odds ratio 0.4 [95%
      confidence interval 0.18-0.85], P = 0.01). Receiver operating characteristic
      curve analysis showed that a whole-blood HCQ concentration cutoff of 1,000 ng/ml
      had a negative predictive value of 96% for exacerbation during followup.
      CONCLUSION: Low whole-blood HCQ concentrations are associated with SLE disease
      activity and are a strong predictor of disease exacerbation. Regular drug
      assaying and individual tailoring of treatment might help to improve the efficacy
      of HCQ treatment in patients with SLE.

PMID- 17009262
TI  - Abrogation of skin disease in LUPUS-prone MRL/FASlpr mice by means of a novel
      tylophorine analog.
AB  - OBJECTIVE: To test the therapeutic effect of DCB-3503, a synthetic compound
      derived from a natural product that inhibits NF-kappaB, on end-organ disease in
      the MRL-Fas(lpr) murine model of systemic lupus erythematosus (SLE). METHODS:
      Eight-week-old female MRL/Fas(lpr) mice were treated intraperitoneally with a low
      (2 mg/kg) or high (6 mg/kg) dose of DCB-3503 for 10 weeks. Control groups were
      administered vehicle treatment alone (negative control) or 25 mg/kg
      cyclophosphamide (positive control). Mice were bled before (8 weeks) and during
      (13 weeks) treatment, and when they were killed (20 weeks), and serum samples
      were analyzed for total IgM and IgG levels and autoantibody titers. When the mice
      were killed, spleen and lymph nodes (axillary, brachial, and cervical) were
      examined by flow cytometric analysis. The presence of skin and renal disease was
      determined by histopathologic analysis. RESULTS: DCB-3503 reduced anti-double
      stranded DNA and antichromatin autoantibodies and nearly abrogated inflammatory
      skin disease in MRL/Fas(lpr) mice; however, it had little effect on histologic
      kidney disease. Treated mice did not have hematologic or hepatic toxicity. These
      data indicate that end-organ disease in MRL/Fas(lpr) mice responds differentially
      to NF-kappaB inhibitor. CONCLUSION: DCB-3503 causes significant abrogation of
      skin disease in MRL/Fas(lpr) mice and may potentially be beneficial in the
      treatment of inflammatory skin disease in SLE.

PMID- 17009264
TI  - Fluctuation in self-perceived stress and increased risk of flare in patients with
      lupus nephritis carrying the serotonin receptor 1A -1019 G allele.
AB  - OBJECTIVE: Stress is believed to be a risk factor for systemic lupus
      erythematosus (SLE) flare. Two serotonin-related gene polymorphisms, the
      serotonin receptor 1A (5-HT1A) polymorphism at -1019C>G and the serotonin
      transporter LS polymorphism, have been reported to affect stress-related
      behaviors. The purpose of this study was to assess the relationship between self
      perceived stress (SPS), variability in SPS, and the 2 serotonin-related gene
      polymorphisms as risk factors for SLE flare. METHODS: Seventy-seven SLE patients
      (50 with lupus nephritis) were evaluated every 2 months (mean +/- SD total
      followup 18.5 +/- 8.5 months), and patients recorded their daily SPS levels (0-10
      scale). Values for mean SPS and coefficient of variation (CV) for SPS were
      calculated from the 60-day block of daily measurements between study visits.
      Serotonin-related gene polymorphism genotypes were determined by polymerase chain
      reaction-based methods. RESULTS: Of the 77 patients, 53 experienced 80 flares of
      SLE (32 renal flares) based on prespecified criteria. Multivariate analysis
      revealed that whereas neither the serotonin-related gene polymorphisms nor the
      mean SPS was predictive of an SLE flare, an increased CV for SPS was predictive
      (P = 0.0031). Interaction between the CV for SPS and the 5-HT1A -1019C>G
      polymorphism was also found to be a predictor of SLE flare (P = 0.0039). Subset
      analysis revealed that only in lupus nephritis patients were increasing CVs for
      SPS (P = 0.0002) and the interaction between CVs for SPS and 5-HT1A (P < 0.0001)
      predictive of a flare. Odds ratio curves demonstrated that the predictive effect
      of increasing CVs for SPS required the presence of the 5-HT1A -1019 G allele, but
      appeared to be independent of the G allele number. CONCLUSION: Fluctuation in the
      level of SPS is a risk factor for the onset of flare in SLE patients with major
      renal manifestations when it occurs on the background of a stress-related
      susceptibility gene (the 5-HT1A -1019 G allele).

PMID- 17009265
TI  - Antiplatelet and anticoagulant therapy in patients with giant cell arteritis.
AB  - OBJECTIVE: Vision loss and cerebrovascular accidents often complicate giant cell
      arteritis (GCA). Antiplatelet and anticoagulant therapy reduce the risk of stroke
      in other populations. We sought to determine whether antiplatelet or
      anticoagulant therapy reduces ischemic complications in patients with GCA.
      METHODS: A retrospective chart review for patients with GCA was conducted.
      Included patients fulfilled modified 1990 American College of Rheumatology
      criteria for GCA. Collected information included demographic data, dates of
      antiplatelet or anticoagulant use, vision loss or stroke, and presence of
      bleeding complications and cerebrovascular risk factors. RESULTS: A total of 143
      patients were included with a mean followup period of 4 years. The cohort
      included 109 women (76%) and 34 men (24%) with a mean age of 71.8 years. A total
      of 104 patients (73%) had a biopsy-proven diagnosis. Eighty-six patients (60.1%)
      had received long-term antiplatelet or anticoagulant therapy, including 18
      (12.6%) who did not start therapy until after an ischemic event had occurred.
      Antiplatelet agents or anticoagulants were not used in 57 patients (39.9%).
      Overall, 11 of 68 patients (16.2%) had an ischemic event while receiving
      antiplatelet or anticoagulant therapy, compared with 36 of 75 patients (48.0%)
      not receiving such therapy (P < 0.0005). Univariate analysis failed to show a
      statistical difference between groups in regard to cerebrovascular risk factors,
      age, sex, or biopsy-proven diagnosis. Bleeding complications occurred in 2
      patients receiving aspirin, 1 patient receiving warfarin, and 5 patients who did
      not receive anticoagulant or antiplatelet therapy. CONCLUSION: Antiplatelet or
      anticoagulant therapy may reduce the risk of ischemic events in patients with
      GCA. An increased risk of bleeding complications was not observed.

PMID- 17009267
TI  - The relationship between frequency and intensity of fears and a collagen
      condition.
AB  - Encouraged by the positive relationship between joint laxity and panic anxiety,
      our objective in this study was to compare widespread cultural fears in subjects
      with and without joint hypermobility syndrome and to assess whether this
      relationship is sustained for common fears as well. A sample consisting of 1,305
      subjects from a rural town were assessed for joint hypermobility syndrome using
      Beighton's criteria. We assessed fear intensity and frequency using a modified
      version of the Fear Survey Schedule (FSS-III). Intense fears, defined with a
      score of 3-4, were compared between hypermobile and nonhypermobile subjects. The
      analysis was carried out separately for men and women. Nonparametric analysis was
      applied throughout. Joint hypermobility syndrome was found in 19.9% (141) of
      women and 6.9% (41) of men. Concerning the fear survey, when we compared the
      groups with and without joint hypermobility, the mean total scores for both
      genders were significantly higher for the hypermobile group. When we analyzed
      each item individually, 43 out of the 44 most severe fears in women and 36 out of
      the 39 in men, scores were significantly higher in the hypermobile group. We
      found significant differences between subjects with and without joint
      hypermobility when assessing specific fears, reinforcing the hypothesis that
      intensity of fears is greater in subjects with joint hypermobility syndrome.
      These results show that the association of joint laxity and phobic anxiety is
      sustained for intense fears and might represent a susceptibility factor for these
      anxiety conditions.

PMID- 17009266
TI  - Revised British Isles Lupus Assessment Group 2004 index: a reliable tool for
      assessment of systemic lupus erythematosus activity.
AB  - OBJECTIVE: To test the interrater reliability of the revised British Isles Lupus
      Assessment Group 2004 (BILAG-2004) index for the assessment of systemic lupus
      erythematosus (SLE) activity. METHODS: Patients with SLE were recruited from 11
      centers. Two physician raters separately assessed the patients' disease activity
      using the BILAG-2004 index in routine clinical practice. Scores ranged from A
      (for very active disease) to E (for inactivity). Two reliability exercises were
      performed. Changes were made to the index after the first exercise (E1), and
      additional training was provided to the raters before the second exercise (E2).
      E1 and E2 involved 12 and 14 raters, respectively. Interrater reliability was
      assessed using kappa statistics and intraclass correlation coefficients. Levels
      of agreement and the extent of major disagreement were also examined. Major
      disagreement was defined as a score difference between raters of A versus C, D,
      or E or B versus D or E. RESULTS: For each exercise, 97 patients were recruited.
      In E1, the mean age of the patients was 42.3 years (range 18.5-82.2 years), 89.7%
      were women, and 74.2% were white, 8.2% were Afro-Caribbean, and 13.4% were South
      Asian, and in E2, the mean age was 43.7 years (range 17.7-75 years), 90.7% were
      women, and 68% were white, 15.5% were Afro-Caribbean, and 11.3% were South Asian.
      The mean disease duration was 9.4 years (range 0-32.1 years) for patients in E1
      and 10 years (range 0-34.8 years) in E2. There was improvement in the interrater
      reliability and the level of agreement from E1 to E2. Further improvement was
      achieved after removal of poorly performing items. CONCLUSION: The BILAG-2004
      index is a reliable tool to assess SLE activity. The use of a well-defined
      glossary and training of raters are essential to ensure the optimal performance
      of the index.

PMID- 17009268
TI  - Interpersonal problems in social phobia versus unipolar depression.
AB  - In this study we compared interpersonal problems in outpatients with social
      phobia (n=50) to those with unipolar depressive disorders (n=50). All
      participants completed the Inventory of Interpersonal Problems. Multivariate
      analyses of variance revealed significant group differences. Individuals with
      social phobia had significantly lower scores on the primary dimension of Control
      and significantly higher values on the Social Avoidance subscale than did
      individuals with depression. Our results support findings from former analogue
      studies. They indicate that social phobia is associated with severe social
      relationship problems that should be considered in treatment.

PMID- 17009269
TI  - Axis I and II comorbidities in subjects with and without nocturnal panic.
AB  - Our purpose in this study was to compare the prevalence and pattern of Axis I and
      II comorbidities between patients with and without nocturnal panic (NP) attacks.
      One hundred and sixteen subjects with panic disorder (PD; according to DSM-IV
      criteria) were included: We assessed Axis I and II comorbidities using the
      Structured Clinical Interview for DSM-IV Axis I and II disorders, respectively.
      Of the sample, 27.6% of subjects had recurrent nocturnal panic attacks (NP
      group). Subjects with NP did not differ from those without in any
      sociodemographic or clinical characteristics. In the sample (94 subjects), 81%
      had at least one lifetime comorbid Axis I disorder, without significant
      differences between subjects with and without nocturnal panic even when
      considering comorbidity rates for single disorders; a trend toward significance
      was found for anorexia nervosa and somatization disorder, which both were more
      frequent among subjects with NP. Concerning Axis II disorders, 49.1% of the
      sample (57 subjects) met the criteria for at least one personality disorder,
      without significant differences between patients with and without NP. No
      significant differences were detected in comorbidity rates for any single Axis II
      personality disorder. Personality might play a relevant role in influencing
      treatment approaches to PD, but it does not appear to be a differential focus of
      concern in patients with compared to those without NP.

PMID- 17009270
TI  - Treatment of giant cell arteritis using induction therapy with high-dose
      glucocorticoids: a double-blind, placebo-controlled, randomized prospective
      clinical trial.
AB  - OBJECTIVE: Glucocorticoid (GC) therapy for giant cell arteritis (GCA) is
      effective but requires prolonged administration, resulting in adverse side
      effects. The goal of the current study was to test the hypothesis that induction
      treatment with high-dose pulse intravenous (IV) methylprednisolone permits a
      shorter course of therapy. METHODS: Twenty-seven patients with biopsy-proven GCA
      were enrolled in a randomized, double-blind, placebo-controlled study to receive
      IV methylprednisolone (15 mg/kg of ideal body weight/day) or IV saline for 3
      consecutive days. All patients were started on 40 mg/day prednisone and followed
      the same tapering schedule as long as disease activity was controlled. The
      numbers of patients with disease in remission after 36, 52, and 78 weeks of
      treatment and taking <or=5 mg/day prednisone were compared. Cumulative prednisone
      dose, number of relapses, and development of adverse GC effects were assessed.
      RESULTS: Ten of the 14 IV GC-treated patients, but only 2 of 13 control patients,
      were taking <or=5 mg/day prednisone at 36 weeks (P = 0.003). This difference was
      maintained; there was a higher number of sustained remissions after
      discontinuation of treatment in the IV GC-treated group and a lower median daily
      dose of prednisone at 78 weeks (P = 0.0004). The median cumulative dose of oral
      prednisone, excluding the IV GC dose, was 5,636 mg in the IV GC-treated group
      compared with 7,860 mg in the IV saline-treated group (P = 0.001). CONCLUSION:
      Initial treatment of GCA with IV GC pulses allowed for more rapid tapering of
      oral GCs and had long-term benefits, with a higher frequency of patients
      experiencing sustained remission of their disease after discontinuation of
      treatment.

PMID- 17009271
TI  - G quadruplex-based FRET probes with the thrombin-binding aptamer (TBA) sequence
      designed for the efficient fluorometric detection of the potassium ion.
AB  - The dual-labeled oligonucleotide derivative, FAT-0, carrying 6-
      carboxyfluorescein (FAM) and 6-carboxytetramethylrhodamine (TAMRA) labels at the
      5' and 3' termini of the thrombin-binding aptamer (TBA) sequence 5'-GGT TGG TGT
      GGT TGG-3', and its derivatives, FAT-n (n=3, 5, and 7) with a spacer at the 5'
      end of a TBA sequence of T(m)A (m=2, 4, and 6) have been designed and
      synthesized. These fluorescent probes were developed for monitoring K(+)
      concentrations in living organisms. Circular dichroism, UV-visible absorption,
      and fluorescence studies revealed that all FAT-n probes could form intramolecular
      tetraplex structures after binding K(+). Fluorescence resonance energy transfer
      and quenching results are discussed taking into account dye-dye contact
      interactions. The relationship between the fluorescence behavior of the probes
      and the spacer length in FAT-n was studied in detail and is discussed.

PMID- 17009272
TI  - Synthesis and evaluation of an alpha-C-galactosylceramide analogue that induces
      Th1-biased responses in human natural killer T cells.
AB  - An alpha-galactosylceramide (alphaGalCer, 1) and its isosteric C-glycoside
      analogue (2) were found to possess promising immunostimulatory activity because
      of their ability to activate natural killer T (NKT) cells. We report the
      synthesis of compound 3, a truncated nonisosteric C-alphaGalCer analogue, that
      like 2 is not enzymatically labile at the glycosidic linkage, but has the
      anomeric carbon directly bonded to the C1 of the phytoceramide backbone. We
      compared the biological activity of the three ligands using an in vitro system
      with human dendritic cells as the antigen-presenting cells and human NKT cells as
      the responding cells. Although 3 was a less potent agonist for NKT cells than 1
      and 2, it induced cytokine production with the highest IFN-gamma:IL-4 and IFN
      gamma:IL-13 ratios. Therefore, our data suggest that the new mimetic of
      alphaGalCer might preferentially promote Th1-immune responses and serve as a
      potent adjuvant in the immunotherapy of cancer and infectious diseases.

PMID- 17009273
TI  - Self-assembled small-molecule microarrays for protease screening and profiling.
AB  - Small-molecule microarrays are attractive for chemical biology as they permit the
      analysis of hundreds to thousands of interactions in a highly miniaturized
      format. Methods to prepare small-molecule microarrays from combinatorial
      libraries by a self-assembly process based on the sequence-specific hybridization
      of peptide nucleic acid (PNA) encoded libraries to oligonucleotide arrays are
      presented. A systematic study of the dynamic range for multiple detection agents,
      including direct fluorescence of attached fluorescein and cyanine-3 dyes,
      antibody-mediated fluorescence amplification, and biotin-gold nanoparticle
      detection, demonstrated that individual PNA-encoded probes can be detected to
      concentrations of 10 pM on the oligonucleotide microarrays. Furthermore, a new
      method for parallel processing of biological samples by using gel-based
      separation of probes is presented. The methods presented in this report are
      exemplified through profiling two closely related cysteine proteases, cathepsin K
      and cathepsin F, across a 625-member PNA-encoded tetrapeptide acrylate library. A
      series of the specific cathepsin K and F inhibitors identified from the library
      were kinetically characterized and shown to correlate with the observed
      microarray profile, thus validating the described methods. Importantly, it was
      shown that this method could be used to obtain orthogonal inhibitors that
      displayed greater than tenfold selectivity for these closely related cathepsins.

PMID- 17009274
TI  - Chemical microarrays to identify ligands that bind pathogenic cells.

PMID- 17009275
TI  - Systematic regulation of the enzymatic activity of phenylacetaldoxime dehydratase
      by exogenous ligands.
AB  - Phenylacetaldoxime dehydratase from Bacillus sp. OxB-1 (OxdB) contains a heme
      that acts as the active site for the dehydration reaction of aldoxime. Ferrous
      heme is the active form, in which the heme is five coordinate with His282 as a
      proximal ligand. In this work, we evaluated the functional role of the proximal
      ligand for the catalytic properties of the enzyme by "the cavity mutant
      technique". The H282G mutant of OxdB lost enzymatic activity, although the heme,
      which was five coordinate with a water molecule (or OH-) as an axial ligand,
      existed in the protein matrix. The enzymatic activity was rescued by imidazole or
      pyridine derivatives that acted as the exogenous proximal ligand. By changing the
      electron-donation ability of the exogenous ligand with different substituents,
      the enzymatic activity could be regulated systematically. The stronger the
      electron-donation ability of the exogenous ligand, the higher was the restored
      enzymatic activity. Interestingly, H282G OxdB with 2-methyl imidazole showed a
      higher activity than the wild-type enzyme. Kinetic analyses revealed that the
      proximal His regulated not only the affinity of substrate binding to the heme but
      also the elimination of the OH group from the substrate.

PMID- 17009276
TI  - Chemoenzymatic ubiquitination of artificial substrates.

PMID- 17009277
TI  - Structural recognition of cholesterol-ceramide monolayers by a specific
      monoclonal antibody.

PMID- 17009278
TI  - Identification of a deacetylase involved in the maturation of teicoplanin.

PMID- 17009279
TI  - Spectral and photophysical studies of substituted indigo derivatives in their
      keto forms.
AB  - The spectral and photophysical properties of indigo derivatives with di-, tetra-,
      and hexa-substitution in their neutral (keto) form are investigated in solution.
      The study comprises absorption and emission spectra, together with quantitative
      measurements of quantum yields of fluorescence (phi(F)) and singlet oxygen
      formation (phi(Delta)) and fluorescence lifetimes. The energy difference between
      the HOMO and LUMO orbitals is dependent on the degree (number of groups) and
      relative position of substitution. The phi(F) and phi(Delta) values were found to
      be very low <or=10(-3). Because of the absence of transient triplet-triplet
      signal, the intersystem crossing yields (phi(T)) were estimated by assuming that
      all the triplet states formed give rise to singlet oxygen formation, that is,
      phi(Delta) approximately phi(T) . It was then possible from phi(IC)=1-phi(F)
      phi(T) to estimate the S(1) approximately approximately -->S(0) internal
      conversion yields and thus, with the other data, to determine the rate constants
      for all decay processes. From these, several conclusions are drawn. Firstly, the
      radiationless rate constants, k(NR) , clearly dominate over the radiative rate
      constants, k(F) , (and processes). Secondly, the main deactivation channel for
      the compounds in their keto form is the radiationless S(1) approximately
      approximately -->S(0) internal conversion process. Finally, although the changes
      are relatively small, internal conversion yield seems to be independent of the
      overall pattern of substitution. A more detailed investigation of the decay
      profiles with collection at the blue and red emission of the fluorescence band of
      indigo and one di-substituted indigo reveals the decays to be bi-exponential and
      that at longer emission wavelengths these appear to be associated with both rise
      and decay times indicating that two excited species exist, which is consistent
      with a keto-excited form giving rise (by fast proton transfer) to the enol-form
      of indigo. Evidence is presented which supports the idea that intramolecular (and
      possibly some intermolecular) proton transfer can explain the high efficiency of
      internal conversion in indigo.

PMID- 17009280
TI  - Adsorption isotherm of CO on Pt(111) electrodes.
AB  - We have determined, for the first time, the equilibrium CO coverage of Pt(111)
      electrodes at room temperature in 0.1 M H(2)SO(4) as a function of the CO partial
      pressure using CO-stripping cyclic voltammetry. Fourier-transform infrared (FT
      IR) spectroscopy was used to confirm qualitatively the coverage values obtained.

PMID- 17009281
TI  - A global search of highly stable gold-covered bimetallic clusters M@Au(n) (n=8
      17): endohedral gold clusters.

PMID- 17009283
TI  - Photocontrolled folding and unfolding of a collagen triple helix.

PMID- 17009284
TI  - The two odors of iron when touched or pickled: (skin) carbonyl compounds and
      organophosphines.

PMID- 17009285
TI  - The question of the Cr oxidation state in the {Cr(SNS)} catalyst for selective
      ethylene trimerization: an unanticipated re-oxidation pathway.

PMID- 17009286
TI  - Charge-induced molecular alignment of intrinsically disordered proteins.

PMID- 17009287
TI  - Single-step synthesis and surface-assisted growth of superconducting TaS2
      nanowires.

PMID- 17009288
TI  - Ligand-free platinum nanoparticles encapsulated in a hollow porous carbon shell
      as a highly active heterogeneous hydrogenation catalyst.

PMID- 17009289
TI  - Acinetobacter bioreporter assessing heavy metals toxicity.
AB  - This work was conducted to employ a whole cell-based biosensor to monitor
      toxicity of heavy metals in water and wastewater. An isolate of industrial
      wastewater bacterium, Acinetobacter sp. DF4, was genetically modified with lux
      reporter gene to create a novel bioluminescent bacterial strain, designated as
      DF4/PUTK2. This bioreporter can investigate the toxicity through light inhibition
      due to cell death or metabolic burden and the specific stress effects of the
      tested soluble materials simultaneously. The use of Acinetobacter DF4/PUTK2 as a
      bioluminescent reporter for heavy metal toxicity testing and for the application
      of wastewater treatment influent toxicity screening is presented in this study.
      Among eight heavy metals tested, the bioluminescence of DF4/PUTK2 was most
      sensitive to Zn, Cd, Fe, Co, Cr followed by Cu in order of decreasing
      sensitivity. The same pattern of sensitivity was observed when several
      contaminated water and wastewater effluents were assayed. This work suggested
      that luxCDABE -marked Acinetobacter bacterium DF4/PUTK2 can be used to bioassay
      the ecotoxicity of wastewater and effluent samples contaminated with heavy
      metals. Using this assay, it is possible to pre-select the more toxic samples for
      further chemical analysis and to discard wastewater samples with low or no
      inhibition because they are not toxic to the environment.

PMID- 17009290
TI  - Lindane removal induction by Streptomyces sp. M7.
AB  - Gamma-hexachlorocyclohexane (gamma-HCH or lindane), one of the most commonly used
      pesticides, has been mainly used in agriculture; this pesticide is known to be
      highly toxic and persistent, causing serious water and soil contamination. The
      objective of the present work is to study the effect of low glucose concentration
      and the addition of lindane at different growing time on the pesticide
      detoxification ability of Streptomyces M7. After 96 h of incubation in synthetic
      medium containing glucose 0.6 g l(-1) with the addition of lindane 100 microg l(
      1) at 20 h of incubation, a typical diauxic curve was obtained: glucose was the
      preferred substrate until 24 h, at 48 h, when the carbohydrate was depleted, the
      microorganism consumed the pesticide like carbon source. On the other hand,
      lindane removal induction was observed, which was greater when the pesticide was
      added to the medium at 20 h than 6 h of incubation. Between 72 and 96 h, a
      maximum of approximately 86% of the Cl(-) was released when lindane was added to
      the medium at 20 h, whereas approximately 70% and 67% Cl(-) was released in the
      medium when the pesticide was added at 0 and 6 h of incubation respectively. This
      is the first report of chloride release from inoculated medium supplemented with
      lindane, suggesting that the pesticide was degraded by Streptomyces sp. under
      aerobic conditions.

PMID- 17009291
TI  - Enterotoxigenic Bacillus spp. DNA fingerprint revealed in naturally contaminated
      nonfat dry milk powder using rep-PCR.
AB  - Dry milk powders and functional ingredients frequently contain high levels of
      viable bacterial spores, some of which may result in growth of toxigenic Bacillus
      spp. in reconstituted and temperature-abused foods. Samples from nonfat dry milk
      (NFDM), infant milk formula (IMF), coffee creamer, lecithin, and cocoa powder
      were subjected to a short heat treatment followed by enrichment in tryptone
      phosphate glucose yeast extract (TPGY) broth at 32 degrees C for 12-25 hours to
      obtain cell densities of 10(6) CFU ml(-1). DNA was extracted using a modification
      of established protocol, leading to the development of an optimized method for
      each food system. Purified DNA was amplified by rep-PCR using extragenic sequence
      targeting primers and optimized for each food. PCR fingerprints from each food
      were analyzed electrophoretically for banding patterns earlier correlated to that
      of enterotoxigenic Bacillus spp. and Bacillus cereus positive control DNA
      fingerprints. Reverse passive latex agglutination (RPLA) and Bacillus Diarrhoeal
      Enterotoxin Enzyme Linked Immunosorbent Assay (Tecra Diagnostics) confirmed the
      presence of HBL and NHE enterotoxin production in NFDM, Coffee creamer, infant
      milk formula, and two lecithin samples but not in cocoa powder. These results
      demonstrate the utility of rep-PCR not only as a tool for bacterial genotyping,
      but a unique means of quality control and hygiene monitoring in food
      microbiology.

PMID- 17009292
TI  - Antimicrobial properties of a non-toxic glycoprotein (WSG) from Withania
      somnifera (Ashwagandha).
AB  - A monomeric glycoprotein with a molecular mass of 28 kDa in SDS-PAGE was isolated
      from the Withania somnifera root tubers. The protein designated WSG (Withania
      somnifera glycoprotein) demonstrated potent antimicrobial activity against the
      phytopathogenic fungi and bacteria tested. Antifungal effect has been
      demonstrated in that WSG exerts a fungistastic effect by inhibiting spore
      germination and hyphal growth in the tested fungi. WSG showed potent antifungal
      activity against Aspergillus flavus, Fusarium oxysporum, F. verticilloides and
      antibacterial activity against Clvibacter michiganensis subsp. michiganensis. WSG
      is an acidic, non-toxic (trypsin-chymotrypsin) protease inhibitor. These results
      encourage further studies of WSG as a potential therapeutic agent for its
      antifungal activity.

PMID- 17009293
TI  - Effect of Cymbopogon citratus L. essential oil on growth and morphogenesis of
      Saccharomyces cerevisiae ML2-strain.
AB  - The growth of Saccharomyces cerevisiae was completely inhibited using 2.0
      microl/ml or 4.0 microl/ml of Cymbopogon citratus essential oil applied by
      fumigation or contact method in Sabouraud's broth medium, respectively. This oil
      was found also to be fungicidal at the same concentrations. The sublethal doses
      1.0 and 3.0 microl/ml inhibited about 98% of yeast growth after 24 hr of
      incubation as compared with the control. Microscopic observations using Light
      Microscope (LM), Scanning Electron Microscope (SEM) and Transmission Electron
      Microscope (TEM) showed morphogenic and ultrastructure changes in the fumigated
      cells with 1.0 microl/ml of the oil. These changes including decrease in cell
      size, depressions on the surface of the cells, alteration in cell wall thickness
      and disruption of plasma membrane. Moreover, Ca(+2), K(+) and Mg(+2) leakages
      increased from the fumigated cells and its total lipid content decreased. Also,
      the fatty acid composition was altered with decrease in the amount of saturated
      fatty acids and increase in the amount of unsaturated fatty acids.

PMID- 17009294
TI  - Use of RNA fingerprinting to identify fungal genes specifically expressed during
      ectomycorrhizal interaction.
AB  - The ecosystem soil is characterized by interactions between microorganisms and
      plants including mycorrhiza--mutualistic interactions between fungi and plant
      roots. Species of the basidiomycete genus Tricholoma form ectomycorrhiza with
      tree roots which is characterized by morphological and metabolic changes of both
      partners, yet molecular mechanisms of the interaction are poorly understood. We
      performed differential display with arbitrarily primed RT-PCR using
      ectomycorrhiza between the basidiomycete Tricholoma vaccinum and its compatible
      host spruce (Picea abies) to isolate mycorrhiza-specific fungal gene fragments.
      76 differentially expressed PCR fragments were verified and checked for plant or
      fungal origin and expression pattern. Of 20 fungal fragments with mycorrhiza
      specific expression, sequence analyses were performed to identify homologs with
      known function of the encoded protein. Among the genes identified were orthologs
      to an aldehyde dehydrogenase, an alcohol dehydrogenase and a protein of the MATE
      transporter family, all with possible function in plant pathogen response. A
      phospholipase B, a beta-glucosidase and a binding protein of basic amino acids
      might play a role in nutrient exchange and growth in planta. A protein similar to
      inactive E2 compounds of ubiquitin-conjugating enzymes like CROC-1 and MMS2, a
      Ras protein and an APS kinase were placed in signal transduction and two
      retrotransposons of the Ty3-gypsy and the Ty1-copia family are expressed most
      likely due to stress.

PMID- 17009295
TI  - Characterization of esterase activity in Geobacillus sp. HBB-4.
AB  - A thermophilic esterase producing bacterium (Bacillus sp. 4), recently isolated
      from Alangullu thermal spring in Aydin (Turkey), was analyzed using 16S rRNA and
      classified as Geobacillus sp. HBB-4, most closely related to Bacillus sp. BGSC
      W9A59 (0.70% sequence divergence) which belongs to the newly described genus
      Geobacillus. The effects of several chemicals on the activity of thermostable
      esterase from Geobacillus sp. HBB-4 were examined. Among the various metal ions
      tested, esterase activity was enhanced by Mn(+2) and Ni(+2), but was inhibited by
      Hg(+2) and Cu(+2), whereas Ca(+2), Mg(+2) and Co(+2) had no effect. In addition,
      other metal ions studied have caused a slight inhibition on the esterase
      activity. EDTA partially inhibited the HBB-4 esterase. The activator metal ions,
      Mn(+2) and Ni(+2) have restored partial inhibition of EDTA. The activity of HBB-4
      esterase was inhibited by ionic detergents while non-ionic detergents activated
      the enzyme. However, a zwitterionic detergent, CHAPS, has caused a slight
      inhibition in the enzyme activity. HBB-4 esterase activity was inhibited at the
      high concentrations of all the organic solvents tested in the present study.
      However, 50% final concentration of DMSO increased the enzyme activity about 7%.
      The HBB-4 esterase has shown more than about 50% of activity in the presence of
      ethanol and methanol solutions. These characteristics of the enzyme along with
      its significant thermostability make the Geobacillus sp. HBB-4 esterase a potent
      candidate for future industrial applications.

PMID- 17009296
TI  - Effect of coating the wells of a polystyrene microtiter plate with xanthorrhizol
      on the biofilm formation of Streptococcus mutans.
AB  - Colonization on the surface of tooth by Streptococcus mutans is an important step
      in the initiation of dental plaque. Polystyrene microtiter plates have been
      employed to study bacterial colonization and biofilm formation of periodontal
      bacteria. The objective of this work was to evaluate the effect of coating the
      wells of a polystyrene microtiter plate with xanthorrhizol isolated from java
      turmeric (Curcuma xanthorrhiza Roxb.) on Strep. mutans biofilm formation. Our
      studies demonstrated that coating of a polystyrene microtiter plate with 5
      microg/ml of xanthorrhizol resulted in significant (up to 60%) reduction of
      adherent cells compared to that of cells in uncoated wells. This result suggests
      that xanthorrhizol displays potent activity in preventing Strep. mutans biofilm
      formation.

PMID- 17009297
TI  - New pFA-cassettes for PCR-based gene manipulation in Candida albicans.
AB  - Several modules for efficient PCR-based gene disruption have recently been
      introduced in Candida albicans. These are based on auxotrophic marker genes for
      deficient strains derived from SC5314/CAI4. Commonly used protocols for the
      transformation C. albicans are based either on the lithium acetate procedure or
      on electroporation also used for Saccharomyces cerevisiae. Here we present our
      updated arsenal of pFA-modules that now include the heterologous marker genes
      HIS1 from C. dubliniensis and LEU2 from C. maltosa (Noble and Johnson 2005) and
      the dominant selection marker ca SAT1 (Reuss et al. 2004). We also introduce the
      Ashbya gossypii TEF1 -promoter as a strong constitutive promoter. With these new
      elements an enlarged collection of pFA-marker and pFA-marker-promoter modules
      were generated containing 17 new modules. In addition, N-terminal tagging with
      GFP-(GA) 6 and epitope-tagging modules using the 6 x-HIS-tag were constructed.
      This adds to the previous modules that only enabled C-terminal GFP-tagging of
      genes (Gola et al. 2003). In total 29 pFA-modules are currently freely available
      from our lab which - together with an update on the diagnostic verification
      procedure - further enlarge the C. albicans molecular toolbox and enhance our
      capabilities to use PCR-based gene alteration methods in C. albicans.

PMID- 17009298
TI  - Biological evaluation of chalcones and analogues as hypolipidemic agents.
AB  - In order to evaluate the anti-hyperlipidemic effect of synthetic chalcones and
      some analogues, nineteen compounds with different substituents in both rings were
      synthesized and hypolipidemic activities were measured in vivo using Triton
      WR1339 acute and hypercaloric chronic assays. 4',4-dichlorochalcone, 3',4',4
      trichlorochalcone, and 4'-chlorochalcone gave an excellent decrease in serum
      total cholesterol and triglycerides in the acute assay. These compounds also
      showed significant anti-lipidemic activity in the chronic assay.

PMID- 17009299
TI  - Synthesis and aldose reductase inhibitory activities of novel O-substituted
      hydroxyphenylacetic acid derivatives.
AB  - In continuation of our work aimed towards the preparation of novel aldose
      reductase inhibitors, several O-substituted hydroxyphenylacetic acid derivatives
      were investigated. The highest inhibitory activity was found for compounds 7b and
      7c bearing a cyclohexylmethyl substituent. This result demonstrates that within
      these series, this moiety is a useful surrogate for the 4-bromo-2-fluorobenzyl
      residue which can be often found in potent aldose reductase inhibitors.

PMID- 17009300
TI  - Discovery of novel aldose reductase inhibitors characterized by an alkoxy
      substituted phenylacetic acid core.
AB  - In continuation of our effort aimed towards the development of novel aldose
      reductase inhibitors, several phenylacetic acids bearing an alkoxy substituent in
      position 3 or 4, respectively, were prepared and screened. The latter represent
      formal ring opening products of the cyclohexylmethyloxyphenylacetic acids IIa and
      IIb, recently elaborated in our group. Out of these series, compounds 4aa and 4ba
      characterized by an n-heptyloxy subunit turned out to be the most potent
      inhibitors. Based on these unexpected results, we suggest that such an alkyl side
      chain acts as a useful surrogate for the 4-bromo-2-fluorobenzyl residue often
      found in potent aldose reductase inhibitors.

PMID- 17009301
TI  - Synthesis of some new quinoxalines and 1,2,4-triazolo[4,3-a]-quinoxalines for
      evaluation of in vitro antitumor and antimicrobial activities.
AB  - Two novel series of quinoxalines derived from 3-phenylquinoxalin-2(1H)-one and 2
      hydrazino-3-phenylquinoxaline, namely 1-substituted-3-phenylquinoxaline-2(1H)
      ones, 2a-c, 3a-d, and 4; 2-(3-oxo-3,3a,4,5,6,7-hexahydroindazol-2-yl)-3
      phenylquinoxaline 6; N- cyclopentylidene or benzylidene-N'-(3-phenylquinoxaline-2
      yl)hydrazines, 7 and 18; 1-substituted-4-phenyl-1,2,4-triazolo[4,3
      a]quinoxalines, 9, 10, 12, 13, 14, and 16 have been synthesized in order to
      evaluate their antitumor and antimicrobial activities. Preliminary screening at
      NCI showed that compounds 2b, 2c, 3b, 3c, and 9 exhibited a moderate to strong
      growth inhibition activity on various tumor panel cell lines between 10(-6) to
      10(-5) molar concentrations. Compound 3b was the most active with a broad
      spectrum of activity. Compound 3c showed selectivity towards CNS-cancer SF-639,
      leukemia CCRF-CEM, and melanoma SK-MEL-5 (GI(50) = 4.03, 6.46, and 4.17 microM,
      respectively). On the other hand, the in vitro microbiological data revealed that
      the prepared compounds showed mild antimicrobial activity.

PMID- 17009302
TI  - Synthesis and evaluation of antimicrobial activity of novel hydrazino and N
      benzylidinehydrazino-substituted 4,8-dihydro-1H,3H-pyrimido[4,5-d]pyrimidin-2,7
      dithiones.
AB  - A number of novel pyrimido[4,5-d]pyrimidine-2,7-dithone derivatives bearing
      hydrazino and N-benzylidinehydrazino substitution were efficiently synthesized
      and screened for in vitro antibacterial activities against the representative
      panel of three Gram-positive and two Gram-negative bacteria. All the synthesized
      compounds showed the potent inhibitory action against Gram-positive bacteria.
      Particularly, N-benzylidinehydrazino-substituted compounds imparted profound
      effect. Furthermore, the Connolly-accessible surface area values were also
      calculated for the target compounds and correlated with the expressed biological
      activity.

PMID- 17009303
TI  - A multi-centre evaluation of absorbent products for men with light urinary
      incontinence.
AB  - AIMS: This study compared the performance of the four main designs of absorbents
      for men with light incontinence: pouches (shields), leafs (guards), washable pant
      with integral pad (pantegral), and small disposable pad. MATERIALS AND METHODS:
      We did a multiple crossover trial. Men with light urinary incontinence were
      recruited. All pouches and leafs available in the UK were identified for
      inclusion. A single pantegral and small pad were selected based on previous
      evaluations for design comparison. Products were tested in random order for up to
      1 week. Performance criteria (e.g., leakage and comfort) were rated using a
      validated product performance questionnaire. Wet product weights and amount of
      leakage were recorded in pad leakage diaries. "Overall opinion" for design
      performance was used as the primary outcome indicator. RESULTS: Seventy-four men
      tested six leafs, six pouches, one pantegral, and one small pad. Leakage data was
      taken from 3,386 wet pads. The pouches generally performed poorly with few
      significant differences between products. The leafs were more variable with large
      and significant differences in ratings. Overall the leaf, pantegral, and small
      pad designs performed significantly better than the pouch (P <or= 0.01) and the
      pantegral design performed significantly worse than the leaf (P = 0.01). One leaf
      product was outstanding and performed significantly better than all other designs
      (P <or= 0.001). CONCLUSION: This is the first published trial of absorbent
      products specifically designed for men. Results show that one particular leaf
      product works best, the pantegral is most suitable only for very light
      incontinence and the pouches are least successful.

PMID- 17009304
TI  - A double-blind, randomized controlled trial of cystometry using saline versus 0.3
      M potassium chloride infusion in women with overactive bladder syndrome.
AB  - AIM: To evaluate the effect of 0.3 M potassium chloride on cystometric parameters
      by comparing it with normal saline as a filling solution in women with overactive
      bladder (OAB). PATIENTS AND METHODS: Twenty-three women with significant OAB
      symptoms underwent consecutive cystometrograms (CMGs) using 0.9% normal saline
      (NS) and 0.3 M potassium chloride (KCl), the order of which was randomized for
      each patient. Individual CMGs were performed by separate investigators and both
      patients and investigators were blinded to the order in which each solution was
      given and to the results of the other CMG. RESULTS: Regardless of the nature of
      the filling solution, the order in which the CMGs were performed had little
      influence on either first desire to void (FDV, mean 83.5 ml vs. 117.8 ml for
      first and second CMGs respectively, P = 0.10) or on maximum cystometric capacity
      (Cmax, mean 265.0 ml vs. 264.4 ml, P = 0.98). KCl produced a significant (24%)
      reduction in mean Cmax compared to NS (mean 228.6 ml vs. 300.8 ml, P = 0.001),
      irrespective of the order of infusion. CONCLUSION: This comparative study using
      0.3 M KCl versus NS as filling solutions suggests that intravesical potassium may
      not simply act on urothelial sensory nerve endings; it may also stimulate
      detrusor muscle contraction. These findings may influence the interpretation of
      the potassium sensitivity test in patients with OAB symptoms, particularly in
      those suspected of having interstitial cystitis.

PMID- 17009305
TI  - Role of aggrecanase 1 in Lyme arthritis.
AB  - OBJECTIVE: Arthritis is one of the hallmarks of late-stage Lyme disease. Previous
      studies have shown that infection with Borrelia burgdorferi, the causative agent
      of Lyme disease, results in degradation of proteoglycans and collagen in
      cartilage. B burgdorferi do not appear to produce any exported proteases capable
      of digesting proteoglycans and collagen, but instead, induce and activate host
      proteases, such as matrix metalloproteinases (MMPs), which results in cartilage
      degradation. The role of aggrecanases in Lyme arthritis has not yet been
      determined. We therefore sought to delineate the contribution of aggrecanases to
      joint destruction in Lyme arthritis. METHODS: We examined the expression patterns
      of aggrecanases 1 and 2 (ADAMTS 4 and 5, respectively) in B burgdorferi-infected
      primary human chondrocyte cell cultures, in synovial fluid samples from patients
      with active Lyme arthritis, and in the joints of mice by real-time quantitative
      reverse transcription-polymerase chain reaction and immunoblotting techniques.
      Bovine cartilage explants were used to determine the role of aggrecanases in B
      burgdorferi-induced cartilage degradation. RESULTS: ADAMTS-4, but not ADAMTS-5,
      was induced in human chondrocytes infected with B burgdorferi. The active forms
      of ADAMTS-4 were increased in synovial fluid samples from patients with active
      Lyme arthritis and were elevated in the joints of mice infected with B
      burgdorferi. Using cartilage explant models of Lyme arthritis, it appeared that
      the cleavage of aggrecan was predominantly mediated by "aggrecanases" rather than
      MMPs. CONCLUSION: The induction of ADAMTS-4 by B burgdorferi results in the
      cleavage of aggrecan, which may be an important first step that leads to
      permanent degradation of cartilage.

PMID- 17009306
TI  - Variability in the efficacy of interferon-alpha in Erdheim-Chester disease by
      patient and site of involvement: results in eight patients.
AB  - OBJECTIVE: Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of
      histiocytosis of unknown origin, characterized by infiltration of tissues by
      spumous histiocytes. ECD features heterogeneous systemic manifestations, and the
      general prognosis remains poor despite various treatment options. METHODS: We
      treated 8 patients with multisystemic ECD with subcutaneous interferon-alpha
      (IFNalpha) at a dosage of 3-9 x 10(6) units 3 times weekly, for a median duration
      of 23 months (range 1-46 months). RESULTS: Treatment was generally well
      tolerated, and side effects remained limited to fever following injections.
      Treatment was discontinued in 1 patient, because of severe depression. During
      treatment, some manifestations of ECD disappeared (i.e., xanthelasma,
      exophthalmos, papilledema, and intracranial hypertension). The efficacy of
      IFNalpha on cardiovascular ECD was variable, however. Treatment resulted in
      partial regression of "coated aorta" in some cases and clear failure in others; 2
      patients died. The level of C-reactive protein diminished sharply in 5 patients.
      CONCLUSION: IFNalpha might be a valuable first-line therapy for prolonged
      treatment of ECD. However, the efficacy of IFNalpha varies among patients and
      according to the sites of disease involvement, and symptoms may fail to respond
      to treatment, especially in patients with severe multisystemic forms of ECD with
      central nervous system and cardiovascular involvement.

PMID- 17009307
TI  - Pediatric granulomatous arthritis: an international registry.
AB  - OBJECTIVE: Blau syndrome and its sporadic counterpart, early-onset sarcoidosis,
      share an identical phenotype featuring the classic triad of arthritis,
      dermatitis, and uveitis and are associated with mutations of CARD15 in 50-90% of
      cases. We chose the term "pediatric granulomatous arthritis" to refer to both. An
      international registry was established in the spring of 2005 to define the
      phenotype spectrum and establish the mutation frequency and variants. METHODS:
      Histologically confirmed granuloma and arthritis were required for inclusion.
      Probands and relatives were genotyped for CARD15. Deidentified clinical
      information was collected. RESULTS: One year after the inception of the registry,
      61 individuals from 22 pedigrees had been entered. Seven pedigrees with 19
      individuals (8 affected, 11 unaffected) had clinical disease that was atypical,
      and none of the individuals in those pedigrees showed mutations. There were 9
      classic simplex pediatric granulomatous arthritis pedigrees including 19
      individuals (9 affected, 10 unaffected) and 6 classic multiplex pedigrees with 22
      individuals (17 affected, 5 unaffected). Cutaneous presentation was the most
      common. Arthritis was polyarticular in 96% of patients. Isolated eye disease was
      never the presenting symptom, but significant/severe visual impairment was
      observed in 41% of patients. Eye disease was bilateral in 21 of 22 patients and
      was complicated by glaucoma in 6 of 22 patients and by cataracts in 50% of
      patients. Skin biopsy was the best diagnostic approach (because of accuracy and
      low invasiveness). CONCLUSION: In this series, the first combining familial and
      sporadic pedigrees and, to our knowledge, the largest, we further defined the
      phenotype and showed that all affected classic (and no nonclassic) pedigrees
      carry a mutation and that there is no asymptomatic carriage. If these data are
      confirmed, mutation analysis rather than tissue sampling may prove to be the most
      efficient diagnostic procedure.

PMID- 17009308
TI  - Composition of calcifications in children with juvenile dermatomyositis:
      association with chronic cutaneous inflammation.
AB  - OBJECTIVE: Calcific deposits develop in 20-40% of children with juvenile
      dermatomyositis (juvenile DM), contributing to disease morbidity and mortality.
      This study was undertaken to define the structure and composition of these
      deposits and to characterize their association with chronic inflammation.
      METHODS: We examined calcific deposits from 5 children with juvenile DM (2 boys
      and 3 girls). The crystal structure and mineral content of the deposits was
      analyzed by x-ray diffraction, Fourier transform infrared spectroscopy, and
      imaging. The protein content of the deposits, following solubilization, was
      assayed by Western blotting. RESULTS: All 5 children had both a young age at
      disease onset (mean +/- SD 3.3 +/- 1.9 years) and, despite therapy, persistent
      cutaneous inflammation (mean +/- SD duration 81.3 +/- 58.7 months). The bone
      proteins, osteopontin, osteonectin, and bone sialoprotein, were identified in the
      protein extracts; the only mineral detected was hydroxyapatite, but the tissue
      was distinct from bone, with an extremely high mineral content and an irregular
      distribution of mineral. CONCLUSION: These results indicate that chronic
      cutaneous inflammation may contribute to the formation of hydroxyapatite
      containing pathologic calcifications in children with juvenile DM.

PMID- 17009309
TI  - The influence of aerobic fitness and fibromyalgia on cardiorespiratory and
      perceptual responses to exercise in patients with chronic fatigue syndrome.
AB  - OBJECTIVE: To investigate cardiorespiratory and perceptual responses to exercise
      in patients with chronic fatigue syndrome (CFS), accounting for comorbid
      fibromyalgia (FM) and controlling for aerobic fitness. METHODS: Twenty-nine
      patients with CFS only, 23 patients with CFS plus FM, and 32 controls completed
      an incremental bicycle test to exhaustion. Cardiorespiratory and perceptual
      responses were measured. Results were determined for the entire sample and for 18
      subjects from each group matched for peak oxygen consumption. RESULTS: In the
      overall sample, there were no significant differences in cardiorespiratory
      parameters between the CFS only group and the controls. However, the CFS plus FM
      group exhibited lower ventilation, lower end-tidal CO2, and higher ventilatory
      equivalent of carbon dioxide compared with controls, and slower increases in
      heart rate compared with both patients with CFS only and controls. Peak oxygen
      consumption, ventilation, and workload were lower in the CFS plus FM group.
      Subjects in both the CFS only group and the CFS plus FM group rated exercise as
      more effortful than did controls. Patients with CFS plus FM rated exercise as
      significantly more painful than did patients with CFS only or controls. In the
      subgroups matched for aerobic fitness, there were no significant differences
      among the groups for any measured cardiorespiratory response, but perceptual
      differences in the CFS plus FM group remained. CONCLUSION: With matching for
      aerobic fitness, cardiorespiratory responses to exercise in patients with CFS
      only and CFS plus FM are not different from those in sedentary healthy subjects.
      While CFS patients with comorbid FM perceive exercise as more effortful and
      painful than do controls, those with CFS alone do not. These results suggest that
      aerobic fitness and a concurrent diagnosis of FM are likely explanations for
      currently conflicting data and challenge ideas implicating metabolic disease in
      the pathogenesis of CFS.

PMID- 17009310
TI  - Transglutaminase 2 limits murine peritoneal acute gout-like inflammation by
      regulating macrophage clearance of apoptotic neutrophils.
AB  - OBJECTIVE: Monosodium urate monohydrate (MSU) crystals have remarkable
      inflammatory potential. However, gouty inflammation is spontaneously self
      limited, an occurrence recognized since antiquity. Gouty synovitis is driven and
      sustained by neutrophil influx. Importantly, macrophage phagocytosis of apoptotic
      (but not necrotic) neutrophils is antiinflammatory. Therefore, we tested the
      hypothesis that efficient clearance of apoptotic neutrophils by macrophages is
      one of the factors that restrains the progression of gouty inflammation.
      Macrophage expression of transglutaminase 2 (TG2), a multifunctional protein with
      reciprocally regulated transamidation and purine nucleotide-binding activities,
      promotes apoptotic leukocyte uptake. In this study, we tested the specific role
      of macrophage TG2 expression in MSU crystal-induced inflammation. METHODS: We
      studied MSU crystal-induced peritonitis in TG2-/- and congenic TG2+/+ mice. We
      also studied the effects of TG2 on apoptotic cell uptake by cultured macrophages.
      RESULTS: TG2-/- mice demonstrated more progressive neutrophilic accumulation than
      did TG2+/+ mice, which was associated with delayed clearance of apoptotic
      neutrophils during MSU crystal-induced peritonitis. We observed defective
      phagocytosis of apoptotic leukocytes by TG2-/- peritoneal macrophages, which was
      corrected by soluble extracellular TG2. Transamidation catalytic activity of TG2
      was not required to mediate macrophage uptake of apoptotic leukocytes. In
      contrast, the TG2 nucleotide binding site residue K173 was critical for this TG2
      function. TG2 bound to GDP, ADP, or ATP (but not to GTP) rescued defective
      apoptotic leukocyte uptake by TG2-/- macrophages. CONCLUSION: Enhancement of
      apoptotic neutrophil uptake by macrophage-derived TG2 restrains gout-like
      neutrophilic peritoneal inflammation. Differential binding of TG2 by purine
      nucleotides may contribute to clinical variability in the extent and duration of
      gouty inflammation.

PMID- 17009311
TI  - Association of methotrexate effects and single-nucleotide polymorphisms in the
      folate pathway in rheumatoid arthritis: comment on the article by Wessels et al.

PMID- 17009312
TI  - Food and Drug Administration centennial: recognizing the guardians of our drug
      supply.

PMID- 17009314
TI  - Do apoptotic cells accumulate in the epidermis of patients with cutaneous lupus
      erythematosus after ultraviolet irradiation? Comment on the article by Kuhn et
      al.

PMID- 17009316
TI  - Protein-protein interactions as targets for small molecule drug discovery.
AB  - Protein-protein interactions represent a highly populated class of targets for
      drug discovery. However, such systems present a number of unique challenges. This
      review presents an analysis of individual protein-protein interaction systems
      which have recently yielded success in discovering drug-like inhibitors. The
      structural characteristics of the protein binding sites and the attributes of the
      small molecule ligands are focused upon, in an attempt to derive commonly shared
      principles that may be of general usefulness in future drug discovery efforts
      within this target class.

PMID- 17009317
TI  - Designing allosteric peptide ligands targeting a globular protein.
AB  - Patented signal analytic algorithms applied to hydrophobically transformed,
      numerical amino acid sequences have previously been used to design short, protein
      targeted, L or D retro-inverso peptides. These peptides have demonstrated
      allosteric and/or indirect agonist effects on a variety of G-protein and tyrosine
      kinase coupled membrane receptors with 30% to over 80% hit rates. Here we extend
      these approaches to a globular protein target. We designed eight peptide ligands
      targeting an ELISA antibody responsive protein, beta-galactosidase, betaGAL.
      Three of the eight 14mer peptides allosterically activated betaGAL with ELISA
      methodology. Using Bayesian statistics, this 38% hit rate would have occurred 2 x
      10(-9) by chance. These peptides demonstrated binding site competitive or
      noncompetitive interactions, suggesting allosteric site multiplicity with respect
      to their betaGAL binding-mediated ELISA signal. Kinetic studies demonstrated the
      temperature dependence of the betaGAL peptide binding functions. Using the van't
      Hoff relation, we found evidence for enthalpy-entropy compensation. This relation
      is often found for hydrophobic interactions in aqueous media, and is consistent
      with the postulated hydrophobic series encoding underlying our protein-targeted,
      peptide design methods. It appears that our algorithmic, hydrophobic
      autocovariance eigenvector template approach to the design of allosteric peptides
      targeting membrane receptors may also be applicable to the design of peptide
      ligands targeting nonmembrane involved globular proteins.

PMID- 17009318
TI  - Cereal-based biorefinery development: integrated enzyme production for cereal
      flour hydrolysis.
AB  - Restructuring the traditional fermentation industry into viable biorefineries for
      the production of fuels, chemicals and plastics is essential in order to replace
      (petro)chemical processing. This work presents engineering aspects of Aspergillus
      awamori submerged fermentation for on-site production of an enzymatic consortium
      that contains glucoamylase, protease and phosphatase. The crude broth filtrate
      was used for the production of wheat flour hydrolysates. Improvements on
      traditional starch hydrolysis carried out in two stages (liquefaction and
      saccharification) were attempted through integration of unit operations and
      reduction of processing temperature and reaction duration. An initial increase of
      temperature to 68 degrees C and a subsequent decrease to 60 degrees C for the
      rest of the enzymatic hydrolysis resulted in a starch to glucose conversion yield
      of 94 and 92% when a wheat flour concentration and commercial starch
      concentration of 225 g L(-1) was used, respectively. The use of crude broth
      filtrates resulted in the simultaneous hydrolysis of wheat protein and phytic
      acid, as was indicated by the increase in free amino nitrogen and phosphorus
      concentration, respectively.

PMID- 17009319
TI  - Predisposition of the dark state of rhodopsin to functional changes in structure.
AB  - As the only member of the family of G-protein-coupled receptors for which atomic
      coordinates are available, rhodopsin is widely studied for insight into the
      molecular mechanism of G-protein-coupled receptor activation. The currently
      available structures refer to the inactive, dark state, of rhodopsin, rather than
      the light-activated metarhodopsin II (Meta II) state. A model for the Meta II
      state is proposed here by analyzing elastic network normal modes in conjunction
      with experimental data. Key mechanical features and interactions broken/formed in
      the proposed model are found to be consistent with the experimental data. The
      model is further tested by using a set of Meta II fluorescence decay rates
      measured to empirically characterize the deactivation of rhodopsin mutants. The
      model is found to correctly predict 93% of the experimentally observed effects in
      119 rhodopsin mutants for which the decay rates and misfolding data have been
      measured, including a systematic analysis of Cys-->Ser replacements reported
      here. Based on the detailed comparison between model and experiments, a
      cooperative activation mechanism is deduced that couples retinal isomerization to
      concerted changes in conformation, facilitated by the intrinsic dynamics of
      rhodopsin. A global hinge site is identified near the retinal-binding pocket that
      ensures the efficient propagation of signals from the central transmembrane
      region to both cytoplasmic and extracellular ends. The predicted activation
      mechanism opens the transmembrane helices at the critical G-protein binding
      cytoplasmic domain. This model provides a detailed, mechanistic description of
      the activation process, extending experimental observations and yielding new
      insights for further tests.

PMID- 17009320
TI  - cdk5 modulates beta- and delta-catenin/Pin1 interactions in neuronal cells.
AB  - The cdk5/p35 complex has been implicated in a variety of functions related to
      brain development, including axonal outgrown and neuronal migration. In this
      study, by co-immunoprecipitation and pull-down experiments, we have shown that
      the cdk5/p35 complex associates with and phosphorylates the neuronal delta
      catenin. Immunocytochemical studies of delta-catenin and the cdk5-activator p35
      in primary cortical neurons indicated that these proteins co-localize in the cell
      body of neuronal cells. In addition, cdk5 co-localized with beta-catenin in the
      cell-cell contacts and plasma membrane of undifferentiated and differentiated N2A
      cells. In this context, we identified Ser(191) and Ser(246) on beta-catenin
      structure as specific phosphorylation sites for cdk5/p35 complex. Moreover, Pin1,
      a peptidyl-prolyl isomerase (PPIase) directly bound to both, beta- and delta
      catenin, once they have been phosphorylated by the cdk5/p35 complex. Studies
      indicate that the cdk5/p35 protein kinase system is directly involved in the
      regulatory mechanisms of neuronal beta- and delta-catenin.

PMID- 17009321
TI  - Blood progenitor cell separation from clinical leukapheresis product by magnetic
      nanoparticle binding and magnetophoresis.
AB  - Positive selection of CD34+ blood progenitor cells from circulation has been
      reported to improve patient recovery in applications of autologous
      transplantation. Current magnetic separation methods rely on cell capture and
      release on solid supports rather than sorting from flowing suspensions, which
      limits the range of therapeutic applications and the process scale up. We tested
      CD34+ cell immunomagnetic labeling and isolation from fresh leukocyte fraction of
      peripheral blood (leukapheresis) using the continuous quadrupole magnetic flow
      sorter (QMS), consisting of a flow channel (SHOT, Greenville, IN) and a
      quadrupole magnet with a maximum field intensity (B(o)) of 1.42 T and a mean
      force field strength (S(m)) of 1.45 x 10(8) TA/m(2). Both the sample
      magnetophoretic mobility (m) and the inlet and outlet flow patterns highly affect
      the QMS performance. Seven commercial progenitor cell labeling reagent
      combinations were quantitatively evaluated by measuring magnetophoretic mobility
      of a high CD34 expression cell line, KG-1a, using the cell tracking velocimeter
      (CTV). The CD34 Progenitor Cell Isolation Kit (Miltenyi Biotec, Bergisch
      Gladbach, Germany) showed the strongest labeling of KG-1a cells and was selected
      for progenitor cell enrichment from 11 fresh and 11 cryopreserved clinical
      leukapheresis samples derived from different donors. The CD34+ cells were
      isolated with a purity of 60-96%, a recovery of 18-60%, an enrichment rate of 12
      169, and a throughput of (1.7-9.3) x 10(4) cells/s. The results also showed a
      highly regular dependence of the QMS performance on the flow conditions that
      agreed with the theoretical predictions based on the CD34+ cell magnetophoretic
      mobility.

PMID- 17009322
TI  - Chemolithotrophic perchlorate reduction linked to the oxidation of elemental
      sulfur.
AB  - Perchlorate (ClO(4)(-)) contamination of ground and surface water has been
      recently recognized as a widespread environmental problem. Biological methods
      offer promising perspectives of perchlorate remediation. Facultative anaerobic
      bacteria couple the oxidation of organic and inorganic electron-donating
      substrates to the reduction of perchlorate as a terminal electron acceptor,
      converting it completely to the benign end-product, chloride. Insoluble inorganic
      substrates are of interest for low maintenance bioreactor or permeable reactive
      barrier systems because they can provide a long-term supply of electron donor
      without generating organic residuals. The main objective of this research was to
      investigate the feasibility of utilizing elemental sulfur (S(0)) as an insoluble
      electron donor for the biological reduction of perchlorate. A chemolithotrophic
      enrichment culture derived from aerobic activated sludge was obtained which
      effectively coupled the oxidation of elemental sulfur to sulfate with the
      reduction of perchlorate to chloride and gained energy from the process for cell
      growth. The enrichment culture grew at a rate of 0.41 or 0.81 1/d in the absence
      and presence of added organic carbon for cell growth, respectively. The
      enrichment culture was also shown to carry out sulfur disproportionation to a
      limited extent as evidenced by the formation of sulfide and sulfate in the
      absence of added electron acceptor. When nitrate and perchlorate were added
      together, the two electron acceptors were removed simultaneously after an initial
      partial decrease in the nitrate concentration.

PMID- 17009323
TI  - Prostate-specific antigen recurrence and mortality after conventional dose
      radiation therapy in select men with low-risk prostate cancer.
AB  - BACKGROUND: Prostate-specific antigen (PSA) recurrence, prostate cancer-specific
      mortality (PCSM), and all-cause mortality (ACM) were evaluated for men age >70
      years receiving conventional dose external beam radiation therapy (RT). METHODS:
      Between January 1, 1989, and December 1, 2002, 358 men were treated with RT for
      localized prostate cancer at a Harvard Medical School Affiliate in Fall River,
      MA. Median age was 71.2 (range, 43.2-83.5) years and patients were followed for a
      median of 4.0 (range, 0.2-13.5) years. RESULTS: Univariable analysis demonstrated
      that increasing pretreatment PSA velocity was significantly associated with
      increasing pretreatment PSA (P < .0001), Gleason score (P = .0002), and shorter
      post-RT PSA doubling time (P = .0007) but not with clinical T-category (P = .09)
      or percent positive biopsies (P = .08). For the select cohort of men age >70
      years with low-risk disease and a pretreatment PSA velocity < or =1.0 ng/mL per
      year, all deaths observed to date have been from nonprostate cancer etiologies.
      Whereas PSA recurrence in this group reached 43.3% by 7 years, due to the
      advanced age of the cohort and less aggressive biology, competing causes of
      mortality predominated as the cause of death despite PSA failure. CONCLUSIONS: In
      men age >70 years with low-risk prostate cancer and pretreatment PSA velocity <
      or =1.0 ng/mL/year, prostate cancer death was not observed despite a modest PSA
      recurrence rate.

PMID- 17009324
TI  - Dynein light chain family in Tetrahymena thermophila.
AB  - Dyneins are large protein complexes that produce directed movement on
      microtubules. In situ, dyneins comprise combinations of heavy, intermediate,
      light-intermediate, and light chains. The light chains regulate the locations and
      activities of dyneins but their functions are not completely understood. We have
      searched the recently sequenced Tetrahymena thermophila macronuclear genome to
      describe the entire family of dynein light chains expressed in this organism. We
      identified fourteen genes encoding putative dynein light chains and seven genes
      encoding light chain-like proteins. RNA-directed PCR revealed that all 21 genes
      were expressed. Quantitative real time reverse transcription PCR showed that many
      of these genes were upregulated after deciliation, indicating that these proteins
      are present in cilia. Using the nomenclature developed in Chlamydomonas,
      Tetrahymena expresses two isoforms each of LC2, LC4, LC7, and Tctex1, three
      isoforms of p28, and six LC8/LC8-like isoforms. Tetrahymena also expresses two
      LC3-like genes. No Tetrahymena orthologue was found for Chlamydomonas LC5 or LC6.
      This study provides a complete description of the different genes and isoforms of
      the dynein light chains that are expressed in Tetrahymena, a model organism in
      which the targeted manipulation of genes is straightforward.

PMID- 17009325
TI  - Molecular characterization of the effects of Y-27632.
AB  - Many key cellular functions, such as cell motility and cellular differentiation
      are mediated by Rho-associated protein kinases (ROCKs). Numerous studies have
      been conducted to examine the ROCK signal transduction pathways involved in these
      motile and contractile events with the aid of pharmacological inhibitors such as
      Y-27632. However the molecular mechanism of action of Y-27632 has not been fully
      defined. To assess the relative contribution of these Rho effectors to the
      effects of Y-27632, we compared the cytoskeletal phenotype, wound healing and
      neurite outgrowth in cells treated with Y-27632 or subjected to knockdown with
      ROCK-I, ROCK-II or PRK-2- specific siRNAs. Reduction of ROCK-I enhances the
      formation of thin actin-rich membrane extensions, a phenotype that closely
      resembles the effect of Y-27632. Knockdown of ROCK II or PRK-2, leads to the
      formation of disc-like extensions and thick actin bundles, respectively. The
      effect of ROCK-I knockdown also mimicked the effect of Y-27632 on wound closer
      rates. ROCK-I knockdown and Y-27632 enhanced wound closure rates, while ROCK-II
      and PRK-2 were not appreciably different from control cells. In neurite outgrowth
      assays, knockdown of ROCK-I, ROCK-II or PRK-2 enhances neurite lengths, however
      no individual knockdown stimulated neurite outgrowth as robustly as Y-27632. We
      conclude that several kinases contribute to the global effect of Y-27632 on
      cellular responses.

PMID- 17009326
TI  - Application of biological activated carbon as a low pH biofilter medium for gas
      mixture treatment.
AB  - Packing material is a crucial component of a bioreactor as it is the microbial
      population's habitat. This study assessed potential improvements to current
      biofiltration processes by investigating use of a novel support medium.
      Biological activated carbon (BAC) with microorganisms growing on granular
      activated carbon can produce a novel medium in which both adsorption and
      biodegradation contribute to pollutants removal. Investigation of carbon
      characteristics demonstrated that BAC was an ideal packing medium for
      biofiltration. The application of the novel packing medium for gas mixture
      treatment was evaluated in a low pH biofilter. Results demonstrated that BAC
      biofilter obtained high removal efficiency for both H(2)S and toluene. The
      removal mechanisms of BAC were investigated after the biofilter operation and it
      demonstrated that the performance of the BAC system was mainly controlled by the
      additive contributions of two removal mechanisms - adsorption and biodegradation.
      This study also indicated the potential for simultaneous treatment of hydrogen
      sulfide and toluene at low pH condition.

PMID- 17009327
TI  - Migration of bone marrow stromal cells in 3D: 4 color methodology reveals
      spatially and temporally coordinated events.
AB  - The cytoskeleton plays a central role in many cell processes including directed
      cell migration. Since most previous work has investigated cell migration in two
      dimensions (2D), new methods are required to study movement in three dimensions
      (3D) while preserving 3D structure of the cytoskeleton. Most previous studies
      have labeled two cytoskeletal networks simultaneously, impeding an appreciation
      of their complex and dynamic interconnections. Here we report the development of
      a 4 color method to simultaneously image vimentin, actin, tubulin and the nucleus
      for high-resolution confocal microscopy of bone-marrow stromal cells (BMSCs)
      migrating through a porous membrane. Several methods were tested for structural
      preservation and labeling intensity resulting in identification of an optimized
      simultaneous fixation and permeabilization method using glutaraldehyde,
      paraformaldehyde and Triton X-100 followed by a quadruple fluorescent labeling
      method. This procedure was then applied at a sequence of time points to migrating
      cells, allowing temporal progression of migration to be assessed by visualizing
      all three networks plus the nucleus, providing new insights into 3D directed cell
      migration including processes such as leading edge structure, cytoskeletal
      distribution and nucleokinesis. Colocalization of actin and microtubules with
      distinct spatial arrangements at the cellular leading edge during migration,
      together with microtubule axial polarization supports recent reports indicating
      the pivotal role of microtubules in directed cell migration. This study also
      provides a foundation for 3D migration studies versus 2D studies, providing
      precise and robust methods to attain new insights into the cellular mechanisms of
      motility.

PMID- 17009328
TI  - The control of microtubule stability in vitro and in transfected cells by MAP1B
      and SCG10.
AB  - In neurons, the regulation of microtubules plays an important role for neurite
      outgrowth, axonal elongation, and growth cone steering. SCG10 family proteins are
      the only known neuronal proteins that have a strong destabilizing effect, are
      highly enriched in growth cones and are thought to play an important role during
      axonal elongation. MAP1B, a microtubule-stabilizing protein, is found in growth
      cones as well, therefore it was important to test their effect on microtubules in
      the presence of both proteins. We used recombinant proteins in microtubule
      assembly assays and in transfected COS-7 cells to analyze their combined effects
      in vitro and in living cells, respectively. Individually, both proteins showed
      their expected activities in microtubule stabilization and destruction
      respectively. In MAP1B/SCG10 double-transfected cells, MAP1B could not protect
      microtubules from SCG10-induced disassembly in most cells, in particular not in
      cells that contained high levels of SCG10. This suggests that SCG10 is more
      potent to destabilize microtubules than MAP1B to rescue them. In microtubule
      assembly assays, MAP1B promoted microtubule formation at a ratio of 1 MAP1B per
      70 tubulin dimers while a ratio of 1 SCG10 per two tubulin dimers was needed to
      destroy microtubules. In addition to its known binding to tubulin dimers, SCG10
      binds also to purified microtubules in growth cones of dorsal root ganglion
      neurons in culture. In conclusion, neuronal microtubules are regulated by
      antagonistic effects of MAP1B and SCG10 and a fine tuning of the balance of these
      proteins may be critical for the regulation of microtubule dynamics in growth
      cones.

PMID- 17009329
TI  - Evidence for a sliding-resistance at the tip of the trypanosome flagellum.
AB  - Motility in trypanosomes is achieved through the undulating behaviour of a single
      "9 + 2" flagellum; normally the flagellar waves begin at the flagellar tip and
      propagate towards the base. For flagella in general, however, propagation is from
      base-to-tip and it is believed that bend formation, and sustained regular
      oscillation, depend upon a localised resistance to inter-doublet sliding - which
      is normally conferred by structures at the flagellar base, typically the basal
      body. We therefore predicted that in trypanosomes there must be a resistive
      structure at the flagellar tip. Electron micrographs of Crithidia deanei,
      Herpetomonas megaseliae, Trypanosoma brucei and Leishmania major have confirmed
      that such attachments are present. Thus, it can be assumed that in trypanosomes
      microtubule sliding at the flagellar tip is resisted sufficiently to permit bend
      formation.

PMID- 17009330
TI  - Living markers for actin block myosin-dependent motility of plant organelles and
      auxin.
AB  - Expression-based techniques using recombinant actin-binding proteins (ABPs) have
      been developed as advantageous means of visualising actin filaments. As actin
      function is linked to the movement of cellular cargoes, and overexpression of
      ABPs may compete with endogenous cytoskeletal proteins, such as myosins,
      secondary effects on cellular motility might be observed during actin
      visualisation. Cytoplasmic streaming and auxin transport were chosen as examples
      of cargo movement and investigated in two Arabidopsis thaliana lines stably
      transformed with fluorescently labelled talin (GFP-mTn) or fimbrin (GFP-FABD2).
      In both lines, the maximal streaming velocity of organelles was reduced to 80% in
      hypocotyl epidermal cells, where actin was broadly equally labelled by both ABPs.
      In contrast, observations of streaming and actin organisation during treatments
      with cytochalasin D (CD) suggested GFP-mTn-labelled actin to remain more stable.
      Furthermore, basipetal auxin transport was undisturbed in the GFP-FABD2 line but
      reduced by GFP-mTn. Remarkably, treatments with CD and 2,3-butanedione monoxime,
      which immobilizes myosin by impairing its ATPase, produced not only failures in
      organelle movement but also in basipetal auxin transport in the wild-type. These
      observations suggest that myosin is involved in processes of auxin translocation.
      In parallel, reduced motility in transgenic plants may be explained by a
      disturbed acto-myosin interplay, if overexpressed ABPs block the processive
      movement of myosin along actin filaments. This report shows that the use of live
      markers for actin visualisation may affect motility of cellular compounds and
      underlines the general need for critical investigation of actin-related processes
      in wild-type as well as transgenic plants prior to further interpretation.

PMID- 17009331
TI  - Shroom4 (Kiaa1202) is an actin-associated protein implicated in cytoskeletal
      organization.
AB  - All animal cells utilize a specialized set of cytoskeletal proteins to determine
      their overall shape and the organization of their intracellular compartments and
      organelles. During embryonic development, the dynamic nature of the actin
      cytoskeleton is critical for virtually all morphogenic events requiring changes
      in cell shape, migration, adhesion, and division. The behavior of the actin
      cytoskeleton is modulated by a myriad of accessory proteins. Shroom3 is an actin
      binding protein that regulates neural tube morphogenesis by eliciting changes in
      cell shape through a myosin II-dependent pathway. The Shroom-related gene SHROOM4
      (formerly called KIAA1202) has also been implicated in neural development, as
      mutations in this gene are associated with human X-linked mental retardation. To
      better understand the function of Shrm4 in embryonic development, we have cloned
      mouse Shroom4 and characterized its protein product in vivo and in vitro. Shroom4
      is expressed in a wide range of cell types during mouse development, including
      vascular endothelium and the polarized epithelium of the neural tube and kidney.
      In endothelial cells and embryo fibroblasts, endogenous Shroom4 co-distributes
      with myosin II to a distinct cytoplasmic population of F-actin and ectopic
      expression of Shroom4 in multiple cell types enhances or induces the formation of
      this actin-based structure. This localization is mediated, at least in part, by
      the direct interaction of Shroom4 and F-actin. Our results suggest that Shroom4
      is a regulator of cytoskeletal architecture that may play an important role in
      vertebrate development.

PMID- 17009332
TI  - Conjugation of methoxypolyethylene glycol to the surface of bovine red blood
      cells.
AB  - Methoxypolyethylene glycol (mPEG) covalently bound to the surface of human red
      blood cells (hRBCs) has been shown to decrease immunological recognition of hRBC
      surface antigens (Bradley et al., 2002). However, there is an increasing shortage
      of hRBC donations, thus making hRBCs scarce and expensive (Davey, 2004; Riess,
      2001). The goal of this study is to similarly PEGylate the surface of bovine RBCs
      (bRBCs) with the aim of reducing the demand on human blood donations needed for
      blood transfusions. This study investigates the feasibility of modifying the
      surface of bRBCs with the succinimidyl ester of methoxypolyethylene glycol
      propionic acid (SPA-mPEG) for use as a potential blood substitute. The oxygen
      binding affinity of PEGylated bRBCs was moderately increased with increasing
      initial SPA-mPEG concentrations up to 4 mM when reacted with bRBCs at a
      hematocrit of 12%. Oxygen transport simulations verified that SPA-mPEG conjugated
      bRBCs could still transport oxygen to pancreatic islet tissues even under extreme
      conditions. PEGylated bRBCs reconstituted to a hematocrit of 40% exhibited
      viscosities on the order of approximately 3 cp, similar to hRBCs at the same
      hematocrit. Taken together, the results of this study demonstrate the success of
      PEGylating bRBCs to yield modified cells with oxygen binding, transport and flow
      properties similar to that of hRBCs.

PMID- 17009333
TI  - Flux analysis shows that hypoxia-inducible-factor-1-alpha minimally affects
      intracellular metabolism in tumor spheroids.
AB  - Heterogeneous metabolic microenvironments in tumors affect local cell growth,
      survival, and overall therapeutic efficacy. Hypoxia-inducible-factor-1alpha (HIF
      1alpha) is a transcription factor that responds to low-oxygen environments by
      upregulating genes for cell survival and metabolism. To date, the metabolic
      effects of HIF-1alpha in three-dimensional tissue have not been investigated.
      Preliminary experiments have shown that the effects of HIF-1alpha are dependent
      on glucose availability. Based on this observation, we hypothesized that HIF
      1alpha would not affect cell survival and metabolism in the center of spheroids,
      where the concentrations of oxygen and glucose are low, similar to hypoxic
      regions found in tumors. To test this hypothesis we used fluorescence microscopy
      and the tumor cylindroid model to quantify cellular viability in three
      dimensional tissue. Isotope labeling and metabolic flux analysis were also used
      to quantity the intracellular metabolism of wild-type and HIF-1alpha-null
      spheroids. As hypothesized, cell survival and intracellular metabolism were not
      different between wild-type and HIF-1alpha-null tissues. In addition, small
      spheroids, which contain less quiescent cells and are less nutritionally limited,
      were found to have increased carbon flux through the biosynthetic pentose
      phosphate and pyruvate carboxylase pathways. These results show how nutrient
      gradients affect cell growth and metabolism in spheroids and suggest that
      metabolic microenvironment should be taken into account when developing HIF
      1alpha-based therapies.

PMID- 17009334
TI  - On the co-occurrence of startles and hippocampal sharp waves in newborn rats.
AB  - Hippocampal sharp waves (SPWs) are among the earliest neural population patterns
      observed in infant mammals. Similarly, startles are among the earliest behavioral
      events observed. Here we provide evidence indicating that these two events are
      linked mechanistically soon after birth in freely moving and head-fixed 1 to 4
      day-old rats. EMG electrodes and intrahippocampal silicon depth electrodes were
      used to detect the presence of startles and SPWs, respectively. In intact pups,
      the majority of sharp waves were preceded by startles (average latency: 161 ms).
      When the hippocampal formation was surgically separated from the brainstem,
      however, sharp waves and startles still occurred, but now independently. In
      addition, unrelated to startles or SPWs, gamma oscillations were detected in
      several subjects, as were neocortical "spindles" that propagated passively into
      the hippocampus. The co-occurrence of sharp waves and startles provides the
      opportunity for Hebbian changes in synaptic efficacy and, thus, is poised to
      contribute to the assembly of neural circuits early in development.

PMID- 17009335
TI  - Effect of temperature on the extraction kinetics and diffusivity of Cyclosporin A
      in the fungus Tolypocladium inflatum.
AB  - The influence of temperature on the extraction kinetics of Cyclosporin A (CyA)
      from the mycelia of Tolypocladium inflatum was examined in this study. The
      extraction of CyA from mycelia was performed in a 2-L stirred, baffled vessel
      using 30% v/v aqueous methanol. The temperature range used was from 5 to 45
      degrees C. A linear relationship was found between the extraction yield of CyA
      and temperature. As the temperature increased, the yield of CyA increased with a
      maximum CyA yield of 18.3% obtained at 45 degrees C, which is 21.3% higher than
      the yield at 25 degrees C. The activation energy for the extraction of CyA from
      T. inflatum was found to be 36.7 kJ/mol, which indicates that the extraction of
      CyA from T. inflatum is controlled by both solubilization of CyA and diffusion of
      CyA through the solid phase of mycelia. The overall mass transfer coefficient,
      k(L)a(S), was found to increase from 1.02 x 10(-3) to 1.34 x 10(-2) s(-1) as the
      temperature increased from 5 to 45 degrees C. The effective diffusivity of CyA in
      the solid matrix of mycelia was found to increase from 1.05 x 10(-15) to 1.43 x
      10(-14) m(2)/s as the temperature increased from 5 to 45 degrees C. A
      mathematical diffusion model was developed and was used to fit the experimental
      kinetic data of CyA extraction and determination of CyA effective diffusivities
      at different temperatures. This is the first time CyA diffusivities as a function
      of extraction temperature are reported in the literature.

PMID- 17009337
TI  - Epinephrine for the treatment of anaphylaxis: do all 40 mg sublingual epinephrine
      tablet formulations with similar in vitro characteristics have the same
      bioavailability?
AB  - Epinephrine autoinjectors are underutilized in the first aid emergency treatment
      of anaphylaxis in the community; so non-invasive sublingual epinephrine
      administration is being proposed. In order to determine the effect of changing
      excipients on the bioavailability of sublingual epinephrine, four distinct fast
      disintegrating epinephrine 40 mg tablet formulations, A, B, C and D, were
      manufactured using direct compression. All formulations were evaluated for tablet
      hardness (H), disintegration time (DT) and wetting time (WT). In a prospective 5
      way crossover study, four sublingual formulations and epinephrine 0.3 mg i.m. as
      a control were tested sequentially in a validated rabbit model. Blood samples
      were collected before dosing and at intervals afterwards. Epinephrine plasma
      concentrations were measured using HPLC-EC. All tablet formulations met USP
      standards for weight variation and content uniformity, and resulted in similar
      mean H, DT and WT (n=6). The area under the curve (AUC), maximum concentration
      (C(max)) and time at which C(max) was achieved (T(max)) did not differ
      significantly after the sublingual administration of formulation A and
      epinephrine 0.3 mg i.m. The AUC after B, C and D were significantly lower
      (p<0.05) than after epinephrine 0.3 mg i.m. These results suggest that the
      selection of excipients used in these tablet formulations can affect the
      bioavailability of sublingually administered epinephrine.

PMID- 17009338
TI  - Effects of naringin on the pharmacokinetics of intravenous paclitaxel in rats.
AB  - It was reported that paclitaxel is an inhibitor of hepatic P-glycoprotein (P-gp)
      and hepatic microsomal cytochrome P450 (CYP) 3A1/2, and that naringin is an
      inhibitor of biliary P-gp and CYP3A1/2 in rats. The purpose of this study was to
      report the effects of oral naringin on the pharmacokinetics of intravenous
      paclitaxel in rats. Oral naringin (3.3 and 10 mg/kg) was pretreated 30 min before
      intravenous (3 mg/kg) administration of paclitaxel. After intravenous
      administration of paclitaxel, the AUC was significantly greater (40.8% and 49.1%
      for naringin doses of 3.3 and 10 mg/kg, respectively), and Cl was significantly
      slower (29.0% and 33.0% decrease, respectively) than controls. The significantly
      greater AUC could be due mainly to an inhibition of metabolism of paclitaxel via
      CYP3A1/2 by oral naringin. The inhibition of hepatic P-gp by oral naringin could
      also contribute to the significantly greater AUC of intravenous paclitaxel by
      oral naringin.

PMID- 17009336
TI  - Contribution of gene expression to metabolic fluxes in hypermetabolic livers
      induced through burn injury and cecal ligation and puncture in rats.
AB  - Severe injury activates many stress-related and inflammatory pathways that can
      lead to a systemic hypermetabolic state. Prior studies using perfused
      hypermetabolic rat livers have identified intrinsic metabolic flux changes that
      were not dependent upon the continual presence of elevated stress hormones and
      substrate loads. We investigated the hypothesis that such changes may be due to
      persistent alterations in gene expression. A systemic hypermetabolic response was
      induced in rats by applying a moderate burn injury followed 2 days later by cecum
      ligation and puncture (CLP) to produce sepsis. Control animals received a sham
      burn followed by CLP, or a sham-burn followed by sham-CLP. Two days after CLP,
      livers were analyzed for gene expression changes using DNA microarrays and for
      metabolism alterations by ex vivo perfusion coupled with Metabolic Flux Analysis.
      Burn injury prior to CLP increased fluxes while decreases in gene expression
      levels were observed. Conversely, CLP alone significantly increased metabolic
      gene expression, but decreased many of the corresponding metabolic fluxes. Burn
      injury combined with CLP led to the most dramatic changes, where concurrent
      changes in fluxes and gene expression levels occurred in about 1/3 of the
      reactions. The data are consistent with the notion that in this model, burn
      injury prior to CLP increased fluxes through post-translational mechanisms with
      little contribution of gene expression, while CLP treatment up-regulated the
      metabolic machinery by transcriptional mechanisms. Overall, these data show that
      mRNA changes measured at a single time point by DNA microarray analysis do not
      reliably predict metabolic flux changes in perfused livers.

PMID- 17009339
TI  - Pharmacokinetic interaction between fluvastatin and diltiazem in rats.
AB  - The present study aimed to investigate the effect of fluvastatin on the
      pharmacokinetics of diltiazem in rats. Pharmacokinetic parameters of diltiazem
      were determined in rats following an oral administration of diltiazem (15 mg/kg)
      in the presence and absence of fluvastatin (0.6 and 2.0 mg/kg). Compared with the
      control given diltiazem alone, the C(max) and AUC of diltiazem increased by 30
      70% in rats with the concurrent use of fluvastatin, while there was no
      significant change in T(max) and the plasma half-life (T(1/2)) of diltiazem.
      Consequently, absolute and relative bioavailability values of diltiazem in the
      presence of fluvastatin were significantly higher (p<0.05) than those from the
      control group, implying that fluvastatin could reduce the presystemic extraction
      of diltiazem. In conclusion, the concurrent use of fluvastatin significantly
      enhanced the oral exposure of diltiazem in rats.

PMID- 17009340
TI  - A composite gene delivery system consisting of polyethylenimine and an
      amphipathic peptide KALA.
AB  - BACKGROUND: Animal viruses such as enveloped virus carry multi-functional
      proteins in the virion that can mediate more than two distinct steps of a gene
      delivery process during the transfer of viral genome into host cells. We tested
      if the aspects of the viral gene delivery mechanism could be mimicked by forming
      composite formulae from multi-functional synthetic gene carriers having
      complementary action modes. METHODS: Polyethylenimine (PEI) was chosen as the
      component responsible for endosome escape and DNA condensation and KALA for
      cellular entry and DNA condensation. Compact DNA-carrier particles consisting of
      the core part where DNA chains were tightly condensed by PEI and the outer layer
      lined with KALA were formulated, characterized and compared with monolithic
      cationic formulae in terms of gene delivery efficiency and mechanism. RESULTS:
      High-level gene expression was observed when C2C12 cells were transfected with
      DNA that was first partially condensed with PEI and, then, fully with KALA. In
      these formulae KALA mediated enhanced cellular entry of DNA by facilitating
      endocytic vesicle formation, while PEI provided an effective endosomolytic
      capacity. An optimal PEI/KALA formula showed transfection efficiencies better
      than or comparable to the commercial cationic liposome in various cell types in
      culture and in vivo. CONCLUSIONS: Gene delivery by combining the membrane-active
      property of KALA with the endosomolytic activity of PEI can be more efficient
      than that by either of the properties alone. It appears that, in these formulae,
      the predominant role of KALA is to facilitate cellular entry of DNA by providing
      a fusogenic capability, rather than an endosomolytic activity.

PMID- 17009341
TI  - Psychological consequences of prenatal diagnosis in a case of familial Angelman
      syndrome.
AB  - Angelman Syndrome (AS), characterized by mental retardation, absence of speech,
      seizures and motor dysfunction, is caused by genetic defects leading to loss of
      expression of the maternal copy of the chromosome 15q11-13 imprinted region. Most
      cases are sporadic, being caused by de novo deletion of maternal chromosome 15q11
      13 (75%) or by paternal uniparental disomy (3-4%). Familial cases can occur, due
      to mutations in the UBE3A gene or in the imprinting center. We describe the case
      of a pregnant woman having two nephews with AS caused by a UBE3A mutation; lack
      of communication within the family led the woman to be completely unaware of the
      risk of disease recurrence until 15 weeks of gestation. UBE3A genetic testing
      revealed she carried the familial mutation 892-893delCT. Prenatal diagnosis was
      performed on amniotic fluid and demonstrated that the fetus had inherited the
      mutation. The unexpected diagnosis and the subsequent termination of the
      pregnancy caused the woman to undergo acute psychological distress showing
      relevant psychopathological symptoms. Nevertheless, at 2-year follow-up, adverse
      consequences were minimized, and the couple was planning a new pregnancy. Factors
      affecting the psychological outcome of abortion and the role of psychological
      support in reducing the risk of long-term unfavorable consequences are discussed.

PMID- 17009342
TI  - Change in psychological resources of younger and older cancer patients during
      chemotherapy.
AB  - Psychological resources were investigated in 150 recently diagnosed adult cancer
      patients and in 150 healthy control group members. Before the start of
      chemotherapy, cancer patients reported higher levels of optimism, purpose in life
      than their healthy peers, and self-esteem (only younger patients) whereas no
      between-group differences emerged for internal locus of control. However, the
      mobilization of psychological resources was limited to younger patients, and
      varied by item content. Over a 9-month period, most psychological resources of
      cancer patients showed a small but significant decline, and patients with higher
      illness-related stressors (e.g. stronger functional impairments, low perceived
      success of therapy) were more likely to decline in resources. We conclude that in
      line with cognitive adaptation theory cancer diagnosis leads to an initial
      mobilization of psychological resources in younger patients, but that over the
      course of therapy psychological resources decline to a level that would be
      expected in healthy adults.

PMID- 17009343
TI  - Measurement of coping and stress responses in women with breast cancer.
AB  - The development of the Responses to Stress Questionnaire-cancer version (RSQ-CV)
      to assess coping with and responses to the stress of breast cancer is described.
      The RSQ-CV was completed by 232 women with breast cancer near the time of their
      diagnosis. Confirmatory factor analyses verified a model that includes three
      voluntary coping factors (primary control engagement coping, secondary control
      engagement coping, disengagement coping) and two involuntary stress response
      factors (involuntary engagement, involuntary disengagement). Internal consistency
      reliability, and stability over 12 weeks for the five factors were adequate to
      excellent. Convergent and discriminant validity was examined through correlations
      with measures of intrusive thoughts, avoidance, and dimensions of perceived
      control. Significant correlations with symptoms of anxiety and depression are
      also reported. Applications of the RSQ-CV for research with breast cancer
      patients are discussed.

PMID- 17009344
TI  - A new osteochondrodysplasia with severe osteopenia, preaxial polydactyly,
      clefting and dysmorphic features resembling filamin-related disorders.
AB  - BACKGROUND: We report a 19-week gestation female foetus with a new syndrome
      characterised by increased nuchal translucency and severe micromelia with
      campomelia evident from the early second trimester. METHODS AND RESULTS:
      Cytogenetic studies performed on amniocytes revealed a normal female karyotype.
      Autopsy after termination of pregnancy showed facial dysmorphism, cleft palate,
      bowed, shortened limbs, hypoplasia of the preaxial elements in all four limbs
      with accompanying accessory ossification centres in the feet, and severe
      calvarial underossification. A diagnosis of otopalatodigital syndrome type 2,
      associated with mutations in FLNA, a gene encoding the cytoskeletal protein
      filamin A, was considered but discarded due to the severity of micromelia, early
      lethality, and the presence of generalised osteopenia instead of hyperostosis.
      The degree of undermodelling and campomelia was reminiscent of another group of
      conditions that include atelosteogenesis types 1 and 3, caused by mutations in
      FLNB. Sequencing analysis did not reveal any pathogenic mutation in the three
      paralogous filamin genes: FLNA, FLNB and FLNC. CONCLUSION: Clinical, radiological
      and cytogenetic findings suggest that this phenotype is a new entity whose
      aetiopathogenesis may be functionally related to the filaminopathies.

PMID- 17009345
TI  - Supernumerary marker chromosomes detected in 100,000 prenatal diagnoses:
      molecular cytogenetic studies and clinical significance.
AB  - OBJECTIVE: To evaluate the clinical significance of the supernumerary marker
      chromosomes (SMCs) detected during prenatal diagnosis. METHODS: We
      retrospectively studied cytogenetic/fluorescence in situ hybridization (FISH)
      results and clinical evaluation of 110 marker cases identified from approximately
      100,000 cases referred for prenatal diagnosis. The clinical follow-up performed
      was focused on cases with de novo markers not derived from chromosome 15.
      RESULTS: Among the 110 SMCs, 79 (71.8%) were de novo, 24 (21.8%) were familial,
      and the origin was undetermined in 7 cases. Fifty-eight of the SMCs originated
      from nonacrocentric chromosomes and 52 SMCs were derived from acrocentric
      chromosomes, with 27 originating from chromosome 15. Twenty-two of the SMCs from
      chromosome 15 did not contain the Prader-Willi/Angelman syndrome critical region,
      and uniparental disomy was ruled out in 19/19 cases. Clinical information ranging
      from birth to 4 years was obtained for 46 de novo cases with nonchromosome-15
      derived SMCs. Of these cases, 11/11 acrocentric SMCs resulted in normal
      phenotype. In contrast, 4/23 cases with single nonacrocentric SMCs and 3/5 cases
      with two or more SMCs resulted in an abnormal phenotype. CONCLUSIONS: Our data
      suggests an overall low risk for acrocentric SMCs and a higher risk for
      nonacrocentric SMCs. Phenotypes associated with markers derived from some
      specific chromosomes are also discussed.

PMID- 17009346
TI  - First-trimester maternal dried blood Down syndrome screening marker levels in
      early pregnancy loss.
AB  - OBJECTIVE: To determine the association of free beta hCG and PAPP-A measured
      during first-trimester Down syndrome risk assessment with early pregnancy loss
      when blood is drawn prior to scheduled ultrasound. METHODS: Maternal dried blood
      samples were collected prior to the ultrasound exam for Down syndrome risk
      assessment. Free beta hCG and PAPP-A levels in 55 patients who experienced loss
      of pregnancy prior to their scheduled ultrasound appointment were compared to
      6464 control pregnancies using logistic regression. RESULTS: Low levels of free
      beta hCG and PAPP-A were associated with increased risk of early pregnancy loss.
      The detection rate of early pregnancy loss for a fixed 5% false-positive rate
      using free beta alone, PAPP-A alone and a combination of the two were 47, 36 and
      49%, respectively. CONCLUSION: Free beta hCG and PAPP-A can identify pregnancies
      at increased risk for early pregnancy loss. More studies are needed to determine
      whether further evaluation of these pregnancies prior to the scheduled ultrasound
      is warranted.

PMID- 17009347
TI  - Chorionic villus sampling for beta-thalassemia: the first report of experience in
      Iran.
AB  - OBJECTIVES: Beta-thalassemia is one of the most common hereditary disorders in
      Iran. The prenatal diagnosis of beta-thalassemia is part of a control program in
      our country and it began 13 years ago. During the past 8 years the number of
      procedures has increased significantly as also the legal abortions. This is the
      first report made on the CVS program in Iran. MATERIALS AND METHODS: One thousand
      six hundred and sixty-one cases of transabdominal Chorionic Villus Sampling (CVS)
      have been retrospectively evaluated. Among them 1381 cases had inclusion
      criteria. CVS results, complications and fetal loss rate were evaluated. The
      distributions of the population at risk were divided between eight regions that
      have been proposed for beta-thalassemia mapping previously. RESULTS: The mean age
      of the patients was 26.2 +/- 5.2 years with mean gestational age of 11.4 +/- 1.4
      weeks. CVS was successful in all the patients (100%) although 1% required a
      second procedure. Post CVS fetal loss was 1.45%. Other minor complications were
      bleeding or spotting (1.81%), amniotic fluid leak (0.5%), small sub-chorionic
      hematoma (0.58%), severe abdominal pain (0.6%) and severe vasovagal reaction
      (0.14%). Late complications were seen in 0.21% (oligohydraminos). Approximately
      2/3 of the patients were referred from three regions of the country, North
      (26.8%), South West (22.4%), Central (19.5%) and the remainder (31.3%) were from
      the other five regions. CONCLUSION: CVS is a safe and effective method for
      prenatal diagnosis of beta-thalassemia in countries with a high prevalence as in
      Iran. The overall complication rate is quite low and acceptable. Fortunately the
      recent acceptance of legal abortion with respect to Muslim rules has increased
      the effectiveness of the procedure and made great advances in its application in
      Iran. Correspondingly, social knowledge has also improved but still there is a
      gap between the population at risk and the required prenatal diagnosis
      laboratories and sampling centers.

PMID- 17009348
TI  - Attitudes to prenatal and preimplantation diagnosis in Saudi parents at genetic
      risk.
AB  - BACKGROUND: Prenatal diagnosis (PND) is only available for severe abnormality in
      Saudi Arabia, and preimplantation genetic diagnosis (PGD) has been proposed as a
      valuable alternative. The acceptability of PGD is unexplored, and may ultimately
      determine the value of this technology in Saudi Arabia. This study reports
      attitudes towards PND and PGD of Saudi couples offered genetic counselling
      following the birth of a child with a single gene or chromosomal condition.
      METHODS: Thirty couples attending the King Faisal Specialist Hospital and
      Research Centre in Riyadh were interviewed using a semi-structured questionnaire.
      One couple had previous experience of PND and none had experience of PGD or IVF.
      RESULTS: Eight of the 30 couples (27%) would only accept PGD; four (13%) only
      PND; three (10%) either technology; the remainder would accept neither test, or
      were unsure. The main concerns of those who would accept neither technology were
      related to personal religious views. Specific concerns about PGD related to the
      IVF procedure, the risk of multiple pregnancies, the chance of mistakes and the
      chance of not getting pregnant. A high proportion of couples (six out of seven;
      86%) who had a child with thalassaemia expressed interest in PGD, and all would
      be prepared to use technology to avoid having an affected child. Views were more
      mixed for the other conditions. CONCLUSION: PGD is acceptable to many couples and
      for some, it represents a valuable alternative to PND. However, parents' concerns
      are complex, and the acceptability of different reproductive technologies must be
      established on an individual basis.

PMID- 17009349
TI  - A simple rule of thumb for diffusion on transition-metal surfaces.

PMID- 17009350
TI  - Nanofibers with tunable stiffness from self-assembly of an amphiphilic wedge-coil
      molecule.

PMID- 17009351
TI  - Microreactor synthesis of beta-peptides.

PMID- 17009352
TI  - One-step, confined growth of bimetallic tin-antimony nanorods in carbon nanotubes
      grown in situ for reversible Li+ ion storage.

PMID- 17009354
TI  - TiO2-Nb2O5 nanotubes with electrochemically tunable morphologies.

PMID- 17009353
TI  - Bioenabled synthesis of rutile (TiO2) at ambient temperature and neutral pH.

PMID- 17009355
TI  - Enantioselective total synthesis and structure determination of the antiherpetic
      anthrapyran antibiotic AH-1763 IIa.

PMID- 17009356
TI  - Cascade signal amplification for DNA detection.

PMID- 17009357
TI  - Quantum chemical methods for the investigation of photoinitiated processes in
      biological systems: theory and applications.
AB  - With the advent of modern computers and advances in the development of efficient
      quantum chemical computer codes, the meaningful computation of large molecular
      systems at a quantum mechanical level became feasible. Recent experimental effort
      to understand photoinitiated processes in biological systems, for instance
      photosynthesis or vision, at a molecular level also triggered theoretical
      investigations in this field. In this Minireview, standard quantum chemical
      methods are presented that are applicable and recently used for the calculation
      of excited states of photoinitiated processes in biological molecular systems.
      These methods comprise configuration interaction singles, the complete active
      space self-consistent field method, and time-dependent density functional theory
      and its variants. Semiempirical approaches are also covered. Their basic
      theoretical concepts and mathematical equations are briefly outlined, and their
      properties and limitations are discussed. Recent successful applications of the
      methods to photoinitiated processes in biological systems are described and
      theoretical tools for the analysis of excited states are presented.

PMID- 17009358
TI  - Local atomic and electronic structure in nanocrystalline Sn-doped anatase TiO2.
AB  - Tin-doped anatase TiO(2) nanopowders and nanoceramics with particle sizes between
      12 and 30 nm are investigated by X-ray absorption fine-structure (EXAFS) and
      Mossbauer spectroscopies. Furthermore, ab initio calculations based on the
      density functional theory are performed to analyze changes in the electronic
      structure due to Sn doping. The three approaches consistently show that Sn is
      dissolved on substitutional bulk sites with a slight increase of the bond lengths
      of the inner coordination shells. The Debye-Waller factors show that the
      nanocrystallites are highly ordered. There is no indication of defect states or
      bandgap changes with Sn doping.

PMID- 17009359
TI  - Insight into the inhibition of human choline kinase: homology modeling and
      molecular dynamics simulations.
AB  - A homology model of human choline kinase (CK-alpha) based on the X-ray
      crystallographic structure of C. elegans choline kinase (CKA-2) is presented.
      Molecular dynamics simulations performed on CK-alpha confirm the quality of the
      model, and also support the putative ATP and choline binding sites. A good
      correlation between the MD results and reported CKA-2 mutagenesis assays has been
      found for the main residues involved in catalytic activity. Preliminary docking
      studies performed on the CK-alpha model indicate that inhibitors can bind to the
      binding sites of both substrates (ATP and choline). A possible reason for
      inhibition of choline kinase by Ca(2+) ion is also proposed.

PMID- 17009360
TI  - The gatekeeper: friend or foe in identifying the next generation of kinase
      inhibitors.

PMID- 17009361
TI  - Scope and mechanistic insights into the use of tetradecyl(trihexyl)phosphonium
      bistriflimide: a remarkably selective ionic liquid solvent for substitution
      reactions.
AB  - A survey of substitution reactions conducted in a phosphonium bistriflimide ionic
      liquid is presented. The results demonstrate high selectivity favoring
      substitution over typically competitive elimination and solvolytic processes even
      when challenging secondary and tertiary electrophiles are employed. The first
      reports of Kornblum substitution reactions in an ionic liquid are described that
      proceed with very high chemoselectivity in favor of nitro over nitroso products
      and elimination side products. The structure-reactivity study indicates that
      these reactions proceed through a narrow spectrum of pathways ranging from
      straight S(N)2 to a preassociation pathway along a saddle point that approaches
      the S(N)1 limit. The barrier to the formation of dissociated carbocations is
      attributed to the structural features of this ionic liquid that favor
      intervention of the associated nucleophile over dissociation, also preventing
      cross over to E1 processes. The lack of any basic entity in the phosphonium
      bistriflimide ionic liquid appears to prevent any potential base-mediated
      elimination reactions, which makes this a highly selective medium for use in
      general substitution reactions.

PMID- 17009362
TI  - Reversible chain transfer between organoyttrium cations and aluminum: synthesis
      of aluminum-terminated polyethylene with extremely narrow molecular-weight
      distribution.
AB  - Aminopyridinato-ligand-stabilized organoyttrium cations are accessible in very
      good yield through alkane elimination from trialkyl yttrium complexes with
      sterically demanding aminopyridines, followed by abstraction of one of the two
      alkyl functions using ammonium borates. At 80 degrees C and in the presence of
      small amounts of aluminum alkyl compounds, very high ethylene polymerization
      activities are observed if very bulky aminopyridinato ligands are used. During
      these polymerizations a reversible polyethylene chain transfer is observed
      between the organoyttrium cations and aluminum alkyls. The chain-transfer
      catalyst system described here is able to produce relatively long-chain (up to
      4000 g mol-1) Al-terminated polyethylene with a molecular-weight
      distribution<1.1. In the synthesis of higher molecular PE a slight increase in
      polydispersity with increasing chain length (15,600 g mol-1, approximately 1.4)
      is observed owing to reduced reversibility caused by higher viscosity and
      precipitation of polymer chains (temperature of 80-100 degrees C).

PMID- 17009363
TI  - Solid-state self-assembly of polymeric double helicates leading to linear arrays
      of silver(I) ions and reversible strand/double helix interconversion in solution.
AB  - Reaction of a bent py-hyz-pym-hyz-pym 1 and of a linear py-hyz-py-hyz-pym 3
      (py=pyridine; pym=pyrimidine; hyz=hydrazone) ligand strands with silver(I)
      tetrafluoroborate in CH(3)NO(2) generates double-helical dinuclear 2 and
      trinuclear 4 complexes. These complexes form polymeric, highly ordered solid
      state structures, with wirelike, linear continuous or discontinuous polycationic
      Ag(n) (+) arrays with Ag--Ag distances of 2.78 to 4.42 A. Ligand 5, an isomer of
      1, is found to yield a [2x2] grid-type complex 6. Titration experiments reveal
      the formation of linear rack-type dinuclear species from 1 and 5. Acid-base
      modulated, reversible interconversion between strand 1 and double helicate 2 may
      be achieved by using tren as a competing complexing agent
      (tren=N(CH(2)CH(2)NH(2))(3)). Progressive addition of silver(I) ions to a 1:1
      mixture of 1 and 5 leads to the preferential formation of the double helicate 2
      over the grid complex 6, illustrating a process of self-organisation with
      selection of the correct ligand.

PMID- 17009364
TI  - Studies of a molecular hourglass: synthesis and magnetic characterisation of a
      cyclic dodecanuclear {Cr10Cu2} complex.
AB  - The synthesis, structure, EPR, and magnetic studies of two dodecanuclear
      heterometallic cyclic clusters are reported. The compounds have the general
      formula [R(2)NH(2)](2)[Cr(10)Cu(2)F(14)(O(2)CCMe(3))(22)] (R=Me, 1 or iPr, 2).
      Both structures contain an array of metal centers which describe an approximate
      "hourglass", with an ammonium cation in the center of each half of the figure.
      The chromium sites are all six-coordinate, with the two copper sites five
      coordinate. The majority of metal-metal edges are bridged by a single fluoride
      and two pivalate ligands, while two Cr--Cu edges are bridged by a single fluoride
      and a single pivalate. Magnetic studies show that 1 and 2 exhibit similar (but
      not identical) behavior, which can be attributed to ten antiferromagnetic and two
      ferromagnetic exchange interactions around the ring which gives an S=0 ground
      state. Quantum Monte Carlo calculations have been used to quantify the exchange
      interactions by successfully simulating the susceptibility for the full
      temperature range and thus clarifying the distinction between 1 and 2. EPR
      spectroscopy shows signals due to excited states, and a variable-temperature
      study has provided an estimate of the energy gap between the first excited state
      (S=1) and second excited state (S=2) for 1 that is consistent with the value
      obtained using the QMC method.

PMID- 17009365
TI  - Synthesis of extended polyphosphacumulenes.
AB  - Addition of two equivalents of (Me(3)Si)(2)CLiCl to the C-[(diphenyl)
      (diisopropylamino)phosphonio]-P-(diisopropylamino)phosphaalkene 2 affords the
      1sigma(4),3sigma(3)-diphosphabuta-1,2,3-triene E1 in 55 % yield. Derivative E1
      was fully characterized, including a single-crystal X-ray diffraction study.
      Alkylation of E1 with methyl trifluoromethanesulfonate gives rise to the first C
      phosphonio-bis(methylene)phosphorane 5, which was isolated in 84 % yield. Because
      the second carbon center is also nucleophilic, cumulene E1 reacts as a "pincer"
      with BF(3)OEt(2), leading to the formation of a novel four-membered PCBC
      heterocycle 6 with a betaine-like structure. Addition of three equivalents of P
      [diphenyl(diisopropylamino)]methylene phosphorane to
      (diisopropylamino)dichlorophosphane, followed by addition of one equivalent of
      CCl(4), and subsequent deprotonation with lithium hexamethyldisilazide gave rise
      to 1sigma(4),3sigma(3),5sigma(4)-triphosphapenta-1,2,3,4-tetraene F1, which was
      isolated in 62 % yield.

PMID- 17009366
TI  - Nucleophilicities and carbon basicities of pyridines.
AB  - Rate and equilibrium constants for the reactions of pyridines with donor
      substituted benzhydrylium ions have been determined spectrophotometrically. The
      correlation equation log k(20 degrees C)=s(N+E), in which s and N are nucleophile
      specific parameters and E is an electrophile-specific parameter, has been used to
      determine the nucleophilicity parameters of various pyridines in CH(2)Cl(2) and
      aqueous solution and to compare them with N of other nucleophiles. It is found
      that the nucleophilic organocatalyst 4-(dimethylamino)pyridine (DMAP) and
      tertiary phosphanes have comparable nucleophilicities and carbon basicities
      despite widely differing Bronsted basicities. For that reason, these reactivity
      parameters are suggested as guidelines for the development of novel
      organocatalysts. The Marcus equation is employed for the determination of the
      intrinsic barriers of these reactions.

PMID- 17009367
TI  - Highly efficient and functional-group-tolerant catalysts for the palladium
      catalyzed coupling of aryl chlorides with thiols.
AB  - The cross-coupling reaction of aryl chlorides with aliphatic and aromatic thiols
      catalyzed by palladium complexes of the strongly binding bisphosphine CyPF-tBu
      ligand (1) is reported. Most of the reactions catalyzed by complexes of ligand 1
      occur with turnover numbers that exceed those of previous catalysts by two orders
      of magnitude. The reactions occur with excellent yields, broad scope and high
      tolerance of functional groups. Coupling of aryl halides with thiols in the
      presence of low loadings of catalysts derived from other Josiphos type ligands,
      as well as ligands of other structural types, are also described.

PMID- 17009368
TI  - Palladium-catalyzed enantioselective domino heck-cyanation sequence: development
      and application to the total synthesis of esermethole and physostigmine.
AB  - An efficient synthesis of functionalized 3-alkyl-3-cyanomethyl-2-oxindole 1 by a
      palladium-catalyzed domino Heck-cyanation reaction has been developed. Reaction
      of ortho-iodoanilide 5 with potassium ferro(II)cyanide, K(4)[Fe(CN)(6)],
      dissolved in DMF in the presence of palladium acetate and sodium carbonate
      afforded oxindole 1 in good to excellent yields. An enantioselective domino Heck
      cyanation process has been developed for the first time using (S)-DIFLUORPHOS as
      a chiral supporting ligand, and an enantioselectivity of up to 79 % ee in the
      enantiomerically enriched oxindole was obtained under optimized conditions. A
      concise total synthesis of esermethole and physostigmine, powerful inhibitors of
      acetyl- and butyryl-cholinesterase, is documented.

PMID- 17009369
TI  - Diastereoselective synthesis of 2-aryl-3-vinyl-2,3-dihydrobenzo[b]furans through
      a Sakurai reaction: a mechanistic proposal.
AB  - The condensation of 2,3-dihydrobenzoxasilepins with aromatic aldehydes in the
      presence of boron trifluoride to form 2,3-dihydrobenzofurans shows a level of
      diastereoselection which is a function of the electronic nature of the aldehyde
      and the polarity of the solvent. The study of the mechanism of the reaction
      demonstrated that it proceeds through a ring-opened allylfluorosilane, which is
      stable enough to be isolated and characterized.

PMID- 17009370
TI  - Mo(15)S(20): first evidence of a new molybdenum cluster type in a metastable
      solid-state compound.
AB  - The Mo(15)S(20) compound was obtained by thermal decomposition of the metastable
      binary Mo(15)S(19) in sealed silica tube at temperatures above 500 degrees C. Its
      crystal structure was solved and refined from a two-component composite crystal
      by X-ray diffraction in the hexagonal space group P6(3)/m and consists of an
      equal mixture of the original Mo(9)S(27) cluster unit and the classical one
      Mo(6)S(8)S(6) interconnected through Mo--S bonds. The Mo core of the Mo(9)S(27)
      unit is totally new and formed a tricapped trigonal prism. Quantum chemical
      calculations carried out in order to understand these trends as well as magnetic
      susceptibility measurements are also reported. The title compound becomes
      superconducting below 5 K.

PMID- 17009371
TI  - G2(+) investigation on the alpha-effect in the SN2 reactions at saturated carbon.
AB  - As a continuing theoretical study on the alpha-effect in the S(N)2 reactions at
      saturated carbon centers, 28 gas-phase reactions have been examined
      computationally by using the high-level G2(+) method. The reactions include: Nu(
      )+CH(3)X-->CH(3)Nu+X(-) (X=F and Cl; Nu(-)=HO(-), HS(-), CH(3)O(-), Cl(-), Br(-),
      HOO(-), HSO(-), FO(-), ClO(-), BrO(-), NH(2)O(-), and HC(==O)OO(-)). It was found
      that all alpha-nucleophiles examined exhibit downward deviations from the
      correlation line between the overall barriers and proton affinities for normal
      nucleophiles, indicating the existence of the alpha-effect in the gas phase. The
      transition states (TS) for the alpha-nucleophiles are characterized by less
      advanced C--X bond cleavages than the normal nucleophiles, leading to smaller
      deformation energies and overall barriers. The size of the alpha-effect is
      related to the electron density on the alpha-atom, and increases when the
      position of alpha-atom is changed from left to right and from bottom to top in
      the periodic table. The reaction with CH(3)F exhibits a larger alpha-effect than
      that with CH(3)Cl, which can be explained by a later TS and a more positively
      charged methyl group at the TS for CH(3)F, [NuCH(3)F](- not equal). Thus, a
      higher electron density on the alpha-atom and a more positive methyl moiety at
      the TS result in a larger alpha-effect.

PMID- 17009372
TI  - Studies of an Fe9 tridiminished icosahedron.
AB  - The synthesis and structural characterization of a nonanuclear FeIII cage complex
      is reported. The nine iron centers in [Fe9(mu3-O)4(O3PPh)3(O2CCMe3)13] lie on the
      vertices of an incomplete icosahedron, with the P atoms of triphenylphosphonate
      at the other three vertices. The paramagnetic core therefore describes a
      tridiminished icosahedron. Magnetic studies suggest an S=1/2 ground state for the
      molecule. Analysis of exchange paths and the susceptibility data point to the
      interpretation that the cluster can be divided into two nearly decoupled
      sections: an {Fe6O3} section, with an S=0 ground state, in which three oxo
      centered triangles bound a central triangle that is not oxo-centered; and an
      {Fe3O} triangle with S=1/2. The analysis of the susceptibility data leads to a
      Heisenberg model based on three significant antiferromagnetic exchange
      interactions, with values of 173.7 cm-1 in the {Fe3O} triangle, and 30.9 and 19.1
      cm-1 within the {Fe6O3} section, while the exchange between them is <1 cm-1. With
      these assignments, the theoretical low-temperature differential susceptibility is
      also in very good agreement with measurements up to 50 T. Magnetic measurements
      in the milli-kelvin range reveal striking hysteresis loops and magnetization
      reversals associated with a Landau-Zener-Stuckelberg (LZS) transition as enhanced
      by the occurrence of a phonon bottleneck.

PMID- 17009373
TI  - Electrocatalytic and magnetic properties of ultrathin nanostructured iron-melanin
      films on Au(111).
AB  - We have prepared ultrathin, nanostructured melanin films on Au(111) by means of
      electrochemical self-assembly. These films were characterized by using Auger
      electron spectroscopy, X-ray absorption near-edge structure spectroscopy,
      scanning tunneling microscopy, magnetic force microscopy, and electrochemical
      techniques. Two types of nanostructures are present in the film: melanin
      nanoparticles and Fe(3)O(4) nanoparticles. The melanin nanoparticles contain Fe
      bonded to oxygen-containing phenolic groups in an octahedral configuration
      similar to that found in Fe(2)O(3). The inorganic-organic composite exhibits
      magnetic properties and catalyzes the electroreduction of hydrogen peroxide in
      alkaline and neutral electrolyte solutions. The electrocatalytic activity depends
      on the Fe-bound melanin and appears to be similar to that found for Fe
      porphyrins.

PMID- 17009374
TI  - On the lack of ring-current aromaticity of (heteroatom) [N]radialenes and their
      dianions.
AB  - Current-density maps, calculated at the ab initio RHF//6-31G**/CTOCD-DZ level,
      show no significant pi ring current in planar equilateral geometries of neutral
      and dianionic [N]radialenes, oxocarbons and thiocarbons C(N)Y(N) (q-) (Y=CH(2),
      O, S; N=4, 5, 6; q=0 (1 a-12 a), 2 (1 b-12 b)). Only the N=3 deltate dianions
      C(3)Y(3) (2-) (Y=CH(2), O, S (1 b, 5 b and 9 b)) have discernible pi ring
      current, and then with at most 20-25 % of the strength of the standard benzene
      current. On the magnetic criterion, lack of current is definitive evidence
      against aromaticity. Pictorial molecular-orbital analysis within the ipsocentric
      approach shows this to be an inevitable consequence of the nodal structure of the
      pi and pi* orbitals of [N]radialene-like systems. On grounds of angular-momentum
      symmetry, spatial distribution, or both, the HOMO-LUMO excitation does not
      contribute a significant central diamagnetic ring current.

PMID- 17009375
TI  - Highly luminescent gold(I)-silver(I) and gold(I)-copper(I) chalcogenide clusters.
AB  - The reactions of [AuClL] with Ag(2)O, where L represents the heterofunctional
      ligands PPh(2)py and PPh(2)CH(2)CH(2)py, give the trigoldoxonium complexes
      [O(AuL)(3)]BF(4). Treatment of these compounds with thio- or selenourea affords
      the triply bridging sulfide or selenide derivatives [E(AuL)(3)]BF(4) (E=S, Se).
      These trinuclear species react with Ag(OTf) or [Cu(NCMe)(4)]PF(6) to give
      different results, depending on the phosphine and the metal. The reactions of
      [E(AuPPh(2)py)(3)]BF(4) with silver or copper salts give [E(AuPPh(2)py)(3)M](2+)
      (E=O, S, Se; M=Ag, Cu) clusters that are highly luminescent. The silver complexes
      consist of tetrahedral Au(3)Ag clusters further bonded to another unit through
      aurophilic interactions, whereas in the copper species two coordination isomers
      with different metallophilic interactions were found. The first is analogous to
      the silver complexes and in the second, two [S(AuPPh(2)py)(3)](+) units bridge
      two copper atoms through one pyridine group in each unit. The reactions of
      [E(AuPPh(2)CH(2)CH(2)py)(3)]BF(4) with silver and copper salts give complexes
      with [E(AuPPh(2)CH(2)CH(2)py)(3)M](2+) stoichiometry (E=O, S, Se; M=Ag, Cu) with
      the metal bonded to the three nitrogen atoms in the absence of AuM interactions.
      The luminescence of these clusters has been studied by varying the chalcogenide,
      the heterofunctional ligand, and the metal.

PMID- 17009377
TI  - Intermolecular oxidative enolate heterocoupling.

PMID- 17009378
TI  - Photochemical synthesis of R-shaped DNA toward DNA recombination and processing
      in vitro.

PMID- 17009379
TI  - A rearrangement to a zirconium-alkenylidene in the insertion of dihalocarbenoids
      and acetylides into zirconacycles.

PMID- 17009380
TI  - Domino cu-catalyzed C--N coupling/hydroamidation: a highly efficient synthesis of
      nitrogen heterocycles.

PMID- 17009381
TI  - Ambient-temperature living anionic polymerization of phosphaalkenes: homopolymers
      and block copolymers with controlled chain lengths.

PMID- 17009382
TI  - The twisted amide 2-quinuclidone: 60 years in the making.

PMID- 17009383
TI  - The use of vinyl sulfonium salts in the stereocontrolled asymmetric synthesis of
      epoxide- and aziridine-fused heterocycles: application to the synthesis of (-)
      balanol.

PMID- 17009384
TI  - Efficient phosphodiester binding and cleavage by a ZnII complex combining
      hydrogen-bonding interactions and double Lewis acid activation.

PMID- 17009385
TI  - Structure-activity relationships in chromatography: retention prediction of
      oligonucleotides with support vector regression.

PMID- 17009386
TI  - Relationship between the ligand structure and the luminescent properties of water
      soluble lanthanide complexes containing bis(bipyridine) anionic arms.
AB  - A series of six new ligands (L(1)-L(6)) suitable for the formation of luminescent
      lanthanide complexes in water is described. Ligands L(1)-L(4) are constructed
      from two 6'-carboxy-6-methylene-2,2'-bipyridine chromophoric arms bonded to the
      amino function of a 2-aminomethylene-6-carboxy-pyridine (L(1)), an N,N-diacetate
      ethylene diamine (L(2)), a serine (L(3)), or an aminomalonic acid (L(4)). For
      ligands L(5) and L(6), the linking amino function is provided by a glutamic acid,
      and the anionic functions at the 6'-position of the bipyridyl arms are made of
      the sodium salts of monoethylphosphonic ester (L(5)) and phosphonic acid (L(6)).
      The synthesis and characterisation of the ligands are described, together with
      the study of the formation of lanthanide complexes with europium and terbium. In
      the case of L(3), the europium complex obtained in acidic conditions was
      crystallised and the X-ray crystal structure is depicted. Photophysical
      properties of the complexes were studied by means of UV-visible absorption, and
      steady-state and time-resolved luminescence spectroscopy. Excited-state
      luminescence lifetimes of the complexes were determined in water and deuterated
      water to gain insight into the number of water molecules directly coordinated in
      the first coordination sphere of the complexes. The coordination behaviour of the
      series of ligands is questioned in the light of the spectroscopic data and
      discussed in terms of protection of the cation towards water molecules and their
      impact on the luminescence efficiency.

PMID- 17009387
TI  - Health care quality, economic inequality, and precautionary saving.
AB  - We argue that health care quality has an important impact on economic inequality
      and on saving behavior. We exploit district-wide variability in health care
      quality provided by the Italian universal public health system to identify the
      effect of quality on income inequality, health inequality and precautionary
      saving. We find that in lower quality districts there is greater income and
      health dispersion and higher precautionary saving. The analysis carries important
      insights for the ongoing debate about the validity of the life-cycle model and
      interesting policy implications for the design of health care systems.

PMID- 17009388
TI  - Minimally invasive surgery for esophageal achalasia.
AB  - Esophageal achalasia is the most commonly diagnosed primary esophageal motor
      disorder and the second most common functional esophageal disorder. Current
      therapy of achalasia is directed toward elimination of the outflow resistance
      caused by failure of the lower esophageal sphincter to relax completely upon
      swallowing. The advent of minimally invasive surgery has nearly replaced
      endoscopic pneumatic dilation as the first-line therapeutic approach. In this
      editorial, the rationale and the evidence supporting the use of laparoscopic
      Heller myotomy combined with fundoplication as a primary treatment of achalasia
      are reviewed.

PMID- 17009389
TI  - New methods for the management of gastric varices.
AB  - Bleeding from gastric varices has been successfully treated by endoscopic
      modalities. Once the bleeding from the gastric varices is stabilized, endoscopic
      treatment and/or interventional radiology should be performed to eradicate
      varices completely. Partial splenic artery embolization is a supplemental
      treatment to prolong the obliteration of the veins feeding and/or draining the
      varices. The overall incidence of bleeding from gastric varices is lower than
      that from esophageal varices. No studies to date have definitively characterized
      the causal factors behind bleeding from gastric varices. The initial episodes of
      bleeding from esophageal varices or gastric varices without prior treatment may
      be at least partly triggered by a violation of the mucosal barrier overlying
      varices. This is especially likely in the case of varices of the fundus. In view
      of the high rate of hemostasis achieved among bleeding gastric varices, treatment
      should be administered in selective cases. Among untreated cases, steps to
      prevent gastric mucosal injury confer very important protection against gastric
      variceal bleeding.

PMID- 17009390
TI  - Complementary analysis of microsatellite tumor profile and mismatch repair
      defects in colorectal carcinomas.
AB  - Microsatellite instability (MSI) is a prognostic factor and a marker of deficient
      mismatch repair (MMR) in colorectal adenocarcinomas (CRC). However, a proper
      application of this marker requires understanding the following: (1) The MSI
      concept: The PCR approach must amplify the correct locus and accurately identify
      the microsatellite pattern in the patient's normal tissue. MSI is demonstrated
      when the length of DNA sequences in a tumor differs from that of nontumor tissue.
      Any anomalous expansion or reduction of tandem repeats results in extra-bands
      normally located in the expected size range (100 bp, above or below the expected
      product), differ from the germline pattern by some multiple of the repeating
      unit, and must show appropriate stutter. (2) MSI mechanisms: MMR gene
      inactivation (by either mutation or protein down-regulation as frequently present
      in deep CRC compartments) leads to mutation accumulation in a cell with every
      cellular division, resulting in malignant transformation. These mechanisms can
      express tumor progression and result in a decreased prevalence of aneuploid cells
      and loss of the physiologic cell kinetic correlations in the deep CRC
      compartments. MSI molecular mechanisms are not necessarily independent from
      chromosomal instability and may coexist in a given CRC. (3) Because of
      intratumoural heterogeneity, at least two samples from each CRC should be
      screened, preferably from the superficial (tumor cells above the muscularis
      propria) and deep (tumor cells infiltrating the muscularis propria) CRC
      compartments to cover the topographic tumor heterogeneity. (4) Pathologists play
      a critical role in identifying microsatellite-unstable CRC, such as occur in
      young patients with synchronous or metachronous tumors or with tumors showing
      classic histologic features. In these cases, MSI testing and/or MMR
      immunohistochemistry are advisable, along with gene sequencing and genetic
      counseling if appropriate. MSI is an excellent functional and prognostically
      useful marker, whereas MMR immunohistochemistry can guide gene sequencing.

PMID- 17009392
TI  - Delayed gastric emptying is associated with pylorus-preserving but not classical
      Whipple pancreaticoduodenectomy: a review of the literature and critical
      reappraisal of the implicated pathomechanism.
AB  - Pylorus-preserving pancreaticoduodenectomy (PPPD) is nowadays considered the
      treatment of choice for periampullary tumors, namely carcinoma of the head, neck,
      or uncinate process of the pancreas, the ampulla of Vater, distal common bile
      duct or carcinoma of the peri-Vaterian duodenum. Delayed gastric emptying (DGE)
      comprises one of the most troublesome complications of this procedure. A search
      of the literature using Pubmed/Medline was performed to identify clinical trials
      examining the incidence rate of DGE following standard Whipple
      pancreaticoduodenectomy (PD) vs PPPD. Additionally we performed a thorough in
      depth analysis of the implicated pathomechanism underlying the occurrence of DGE
      after PPPD. In contrast to early studies, the majority of recently performed
      clinical trials demonstrated no significant association between the occurrence of
      DGE with either PD or PPPD. PD and PPPD procedures are equally effective
      operations regarding the postoperative occurrence of DGE. Further randomized
      trials are required to investigate the efficacy of a recently reported (but not
      yet tested in large-scale studies) modification, that is, PPPD with antecolic
      duodenojejunostomy.

PMID- 17009393
TI  - Induction of apoptosis on human hepatocarcinoma cell lines by an alkyl resorcinol
      isolated from Lithraea molleoides.
AB  - AIM: To study the mechanism of cytotoxicity of a new active 5-alkyl resorcinol
      [1, 3-dihydroxy-5- (tridec-4', 7'-dienyl) benzene] isolated from Lithraea
      molleoides leaves on liver tumor cells. METHODS: Human hepatocarcinoma cell lines
      (HepG2 and Hep3B) in culture were treated with inhibitory concentrations, 50% of
      the compound, for 24 h. The induction of apoptosis was detected in treated cells
      by analysis of DNA fragmentation, DNA content, and acridine orange and propidium
      iodide staining. RESULTS: After 24 h of 5-alkyl resorcinol treatment, both cell
      lines showed: (1) the typical morphological alterations of apoptosis; (2) DNA
      fragmentation, detected by laddering and appearance of a subG0 population by flow
      cytometry; and (3) condensed and fragmented nuclei by acridine orange-propidium
      iodide staining. CONCLUSION: Based on the results, this compound exerts its
      cytotoxic effect in both hepatocellular cell lines through apoptotic cell death.
      For Hep3B, cells with mutated p53 and Fas, apoptosis would proceed by p53- or Fas
      independent pathways.

PMID- 17009391
TI  - Probiotics and prebiotics in chronic inflammatory bowel diseases.
AB  - The prokaryotic and eukaryotic cells of the colon exist in a highly complex, but
      harmonious relationship. Disturbances in this remarkable symbiosis can result in
      the development of inflammatory bowel diseases (IBD). Although the etiology of
      IBD is not entirely understood, it is known that the chronic inflammation of
      Crohn's disease, ulcerative colitis and chronic pouchitis are a result of an
      overly aggressive immune response to the commensal intestinal flora in
      genetically susceptible hosts. Recent studies have enhanced our ability to
      understand the interaction between the host and its intestinal microflora and the
      role the microflora plays in maintaining intestinal homeostasis. As we begin to
      understand the benefits conferred to the intestine by the microflora, the notion
      of modifying the composition of the bacterial load to improve human health has
      arisen. A significant body of research now exists investigating the role of
      probiotics and prebiotics in ameliorating chronic intestinal inflammation. This
      article will begin with an overview of the role of the commensal microflora in
      maintaining mucosal immune homeostasis, and how a dysregulated immune response to
      the intestinal microflora results in IBD. This will be followed by a summary of
      the use of probiotics and prebiotics in experimental and human IBD.

PMID- 17009394
TI  - Distribution of hepatitis B virus genotypes: phylogenetic analysis and
      virological characteristics of genotype C circulating among HBV carriers in
      Kolkata, Eastern India.
AB  - AIM: To evaluate the genotype distribution of hepatitis B virus (HBV) in Eastern
      India and to clarify the phylogenetic origin and virological characteristics of
      the recently identified genotype C in this region. METHODS: Genotype
      determination, T1762/A1764 mutation in the basal core promoter (BCP) and A1896
      mutation in the precore region of 230 subjects were determined by restriction
      fragment length polymorphism method (RFLP) and the result was confirmed by direct
      sequencing. RESULTS: The predominant genotypes D (HBV/D) and A (HBV/A) were
      detected in 131/230 (57%) and 57/230 (25%) samples. In addition, genotype C
      (HBV/C) was detected in 42/230 (18%) isolates. Surface gene region was sequenced
      from 45 isolates (27 HBV/C, 9 HBV/A and 9 HBV/D). Phylogenetic analysis revealed
      that all of the HBV/C sequences clustered with South East Asian subgenotype
      (HBV/Cs). The sequence data showed remarkable similarity with a Thai strain
      (AF068756) (99.5% +/- 0.4% nucleotide identities) in 90% of the genotype C
      strains analyzed. T1762/A1764 mutation in BCP region, associated with high ALT
      was significantly higher in HBeAg negative isolates than HBeAg positive isolates.
      Frequency of A1896 mutation leading to HBeAg negativity was low. CONCLUSION: The
      present study reports the genotypic distribution and the characteristics of
      partial genome sequences of HBV/C isolates from Eastern India. Low genetic
      diversity and confinement of HBV/C in Eastern India possibly indicate a recent,
      limited, spread in this region. Genotype C with T1762/A1764 mutation has been
      reported to increase the risk for hepatocellular carcinoma; therefore genotype C
      carriers in Eastern India should be carefully monitored.

PMID- 17009395
TI  - H pylori stimulates proliferation of gastric cancer cells through activating
      mitogen-activated protein kinase cascade.
AB  - AIM: To explore the mechanism by which H pylori causes activation of gastric
      epithelial cells. METHODS: A VacA (+) and CagA (+) standard H pylori line NCTC
      11637 and a human gastric adenocarcinoma derived gastric epithelial cell line BGC
      823 were applied in the study. MTT assay and (3)H-TdR incorporation test were
      used to detect the proliferation of BGC-823 cells and Western blotting was used
      to detect the activity and existence of related proteins. RESULTS: Incubation
      with H pylori extract increased the proliferation of gastric epithelial cells,
      reflected by both live cell number and DNA synthesis rate. The activity of
      extracellular signal-regulated protein kinase (ERK) signal transduction cascade
      increased within 20 min after incubation with H pylori extract and appeared to be
      a sustained event. MAPK/ERK kinase (MEK) inhibitor PD98059 abolished the action
      of H pylori extract on both ERK activity and cell proliferation. Incubation with
      H pylori extract increased c-Fos expression and SRE-dependent gene expression. H
      pylori extract caused phosphorylation of several proteins including a protein
      with molecular size of 97.4 kDa and tyrosine kinase inhibitor genistein inhibited
      the activation of ERK and the proliferation of cells caused by H pylori extract.
      CONCLUSION: Biologically active elements in H pylori extract cause proliferation
      of gastric epithelial cells through activating tyrosine kinase and ERK signal
      transduction cascade.

PMID- 17009396
TI  - Lactobacilli, bifidobacteria and E. coli nissle induce pro- and anti-inflammatory
      cytokines in peripheral blood mononuclear cells.
AB  - AIM: To investigate whether the stimulation of peripheral blood mononuclear cells
      (PBMNC) with the cell debris and cell extraction of different probiotic strains
      is similar or species specific. METHODS: Three strains of bifidobacteria, 4
      strains of lactobacilli, and E. coli nissle were sonicated and centrifuged in
      order to divide them into cell extract and cell debris. PBMNC were separated by
      density gradient and incubated for 36 h with either the cell debris or the cell
      extract of single strains of probiotic bacteria in doses from 10(2) to 10(8)
      CFU/mL. Cell supernatants were taken and interleukin (IL)-10, IL-1beta, and tumor
      necrosis factor (TNF)-alpha were determined by ELISA. RESULTS: Depending on the
      species super-family, the strains had different stimulation patterns. Except for
      both L. casei strains, the cell extract of bifidobacteria and lactobacilli had
      less stimulating capacity than cell debris, whereas the cell extract of E. coli
      nissle had similar stimulating properties to that of the cell debris of the
      strain and significantly more stimulating capacity than that of bifidobacteria
      and lactobacilli. The cell debris of bifidobacteria stimulated more cytokine
      release than the cell debris of lactobacilli. The cell debris of lactobacilli did
      not have a stimulating capacity when lower concentrations were used. Neither cell
      extraction nor cell debris had an inhibitory effect on the production of the
      tested cytokines by stimulated PBMNC. CONCLUSION: The incubation of probiotic
      strains, which have been used in clinical trials for inflammatory diseases, with
      immunocompetent cells leads to different species specific reactions. High IL-10
      response to cell debris of bifidobacteria and E. coli nissle can be found. This
      corresponds to positive effects of bifidobacteria and E. coli nissle in clinical
      trials for inflammatory bowel disease compared to negative outcomes obtained with
      lactobacilli.

PMID- 17009397
TI  - Effects of probiotic bacteria on gastrointestinal motility in guinea-pig isolated
      tissue.
AB  - AIM: To evaluate the intestinal motility changes evoked by 8 bacterial strains
      belonging to Bifidobacterium, Lactobacillus and Streptococcus genera within the
      probiotic preparation VSL#3. METHODS: Ileum and proximal colon segments isolated
      from guinea-pigs were used as a study model. Entire cells and cell fractions
      (cell debris, cell wall fraction, cytoplasmatic fraction, proteinaceous and non
      proteinaceous cytoplasmatic components) of VSL#3 strains and, as controls,
      Escherichia coli, Salmonella aboni and Bacillus licheniformis were tested in this
      in vitro model. RESULTS: Among the bacterial cell fractions tested, only the
      cytoplasmatic fraction modified intestinal motility. Lactobacillus strains
      stimulated the contraction of ileum segment, whereas all probiotic strains tested
      induced proximal colon relaxation response. The non-proteinaceous cytoplasmatic
      components were responsible for the colon relaxation. CONCLUSION: The results
      obtained in this study suggest that the proximal colon relaxation activity showed
      by the probiotic bacteria could be one of the possible mechanisms of action by
      which probiotics exert their positive effects in regulating intestinal motility.

PMID- 17009398
TI  - Increased DNA binding activity of NF-kappaB, STAT-3, SMAD3 and AP-1 in acutely
      damaged liver.
AB  - AIM: To investigate the role of genes and kinetics of specific transcription
      factors in liver regeneration, and to analyze the gene expression and the
      activity of some molecules crucially involved in hepatic regeneration. METHODS:
      USING gel-shift assay and RT-PCR, transcription factors, such as NF-kappaB, STAT
      3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS),
      hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of
      chemically induced hepatectomy. RESULTS: Gene expression of HGF and its receptor
      c-met peaked at 3 h and 24 h after acute CCl(4) intoxi-cation. iNOS expression
      was only observed from 6 to 48 h. Transcriptional factor NF-kappaB had an early
      activation at 30 min after acute liver damage. STAT-3 peaked 3 h post
      intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a
      high activity at all analyzed times. CONCLUSION: TNF-alpha and IL-6 play a
      central role in hepatic regeneration. These two molecules are responsible for
      triggering the cascade of events and switch-on of genes involved in cell
      proliferation, such as growth factors, kinases and cyclins which are direct
      participants of cell proliferation.

PMID- 17009399
TI  - Reduced expression of Ca2+-regulating proteins in the upper gastrointestinal
      tract of patients with achalasia.
AB  - AIM: To compare expression of Ca(2+)-regulating proteins in upper
      gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to
      elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca(2+) ATPase
      (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and
      calreticulin (CRT) were assessed by quantitative Western blotting in esophagus
      and heart of rats, rabbits, and humans. Furthermore, expression profiles of these
      proteins in biopsies of lower esophageal sphincter and esophagus from patients
      with achalasia and healthy volunteers were analyzed. RESULTS: SERCA 2a protein
      expression was much higher in human heart (cardiac ventricle) compared to
      esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The
      highest CRT expression was noted in the human esophagus, while PLB, although
      highly expressed in the heart, was below our detection limit in upper GI tissue.
      Compared to healthy controls, CSQ and CRT expression in lower esophageal
      sphincter and distal esophageal body were significantly reduced in patients with
      achalasia (P < 0.05). CONCLUSION: PLB in the human esophagus might be of lesser
      importance for regulation of SERCA than in heart. Lower expression of Ca(2+)
      storage proteins (CSQ and CRT) might contribute to increased lower esophageal
      sphincter pressure in achalasia, possibly by increasing free intracellular
      Ca(2+).

PMID- 17009400
TI  - Postprandial transduodenal bolus transport is regulated by complex peristaltic
      sequence.
AB  - AIM: To study the relationship between the patterns of postprandial peristalsis
      and transduodenal bolus transport in healthy subjects. METHODS: Synchronous
      recording of chyme transport and peristaltic activity was performed during the
      fasting state and after administration of a test meal using a special catheter
      device with cascade configuration of impedance electrodes and solid-state
      pressure transducers. The catheter was placed into the duodenum, where the first
      channel was located in the first part of the duodenum and the last channel at the
      duodenojejunal junction. After identification of previously defined chyme
      transport patterns the associated peristaltic patterns were analyzed. RESULTS:
      The interdigestive phase 3 complex was reliably recorded with both techniques. Of
      497 analyzed impedance bolus transport events, 110 (22%) were short-spanned
      propulsive, 307 (62%) long-spanned propulsive, 70 (14%) complex propulsive, and
      10 (2%) retrograde transport. Short-spanned chyme transports were predominantly
      associated with stationary or propagated contractions propagated over short
      distance. Long-spanned and complex chyme transports were predominantly associated
      with propulsive peristaltic patterns, which were frequently complex and comprised
      multiple contractions. Propagated double wave contraction, propagated contraction
      with a clustered contraction, and propagated cluster of contractions have been
      identified to be an integralted part of a peristaltic sequence in human duodenum.
      CONCLUSION: Combined impedancometry and manometry improves the analysis of the
      peristaltic patterns that are associated with postprandial transduodenal chyme
      transport. Postprandial transduodenal bolus transport is regulated by propulsive
      peristaltic patterns, which are frequently complex but well organized. This
      finding should be taken into consideration in the analysis of intestinal motility
      studies.

PMID- 17009401
TI  - Comparative clinical trial of S-pantoprazole versus racemic pantoprazole in the
      treatment of gastro-esophageal reflux disease.
AB  - AIM: To compare the efficacy and tolerability of S-pantoprazole (20 mg once a
      day) versus racemic pantoprazole (40 mg once a day) in the treatment of gastro
      esophageal reflux disease (GERD). METHODS: This multi-centre, randomized, double
      blind clinical trial consisted of 369 patients of either sex suffering from GERD.
      Patients were randomly assigned to receive either one tablet (20 mg) of S
      pantoprazole once a day (test group) or 40 mg racemic pantoprazole once a day
      (reference group) for 28 d. Patients were evaluated for reduction in baseline on
      d 0, GERD symptom score on d 14 and 28, occurrence of any adverse effect during
      the course of therapy. Gastrointestinal (GI) endoscopy was performed in 54
      patients enrolled at one of the study centers at baseline and on d 28. RESULTS:
      Significant reduction in the scores (mean and median) for heart burn (P <
      0.0001), acid regurgitation (P < 0.0001), bloating (P < 0.0001), nausea (P <
      0.0001) and dysphagia (P < 0.001) was achieved in both groups on d 14 with
      further reduction on continuing the therapy till 28 d. There was a statistically
      significant difference in the proportion of patients showing improvement in acid
      regurgitation and bloating on d 14 and 28 (P = 0.004 for acid regurgitation; P =
      0.03 for bloating) and heart burn on d 28 (P = 0.01) between the two groups, with
      a higher proportion in the test group than in the reference group. Absolute risk
      reductions for heartburn/acid regurgitation/bloating were approximately 15% on d
      14 and 10% on d 28. The relative risk reductions were 26%-33% on d 14 and 15% on
      d 28. GI endoscopy showed no significant difference in healing of esophagitis (P
      = 1) and gastric erosions (P = 0.27) between the two groups. None of the patients
      in either group reported any adverse effect during the course of therapy.
      CONCLUSION: In GERD, S-pantoprazole (20 mg) is more effective than racemic
      pantoprazole (40 mg) in improving symptoms of heartburn, acid regurgitation,
      bloating and equally effective in healing esophagitis and gastric erosions. The
      relative risk reduction is 15%-33%. Both drugs are safe and well tolerated.

PMID- 17009402
TI  - Short mucin 6 alleles are associated with H pylori infection.
AB  - AIM: To investigate the relationship between mucin 6 (MUC6) VNTR length and H
      pylori infection. METHODS: Blood samples were collected from patients visiting
      the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was
      isolated from whole blood, the repeated section was cut out using a restriction
      enzyme (Pvu II) and the length of the allele fragments was determined by Southern
      blotting. H pylori infection was diagnosed by (14)C urea breath test. For
      analysis, MUC6 allele fragment length was dichotomized as being either long (>
      13.5 kbp) or short (< or = 13.5 kbp) and patients were classified according to
      genotype [long-long (LL), long-short (LS), short-short (SS)]. RESULTS: 160
      patients were studied (mean age 43 years, 36% were males, 58% H pylori positive).
      MUC6 Pvu II-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the
      patients with the LL, LS, SS MUC6 genotype, 43% (24/56), 57% (25/58) and 76%
      (11/46) were infected with H pylori, respectively (P = 0.003). CONCLUSION: Short
      MUC6 alleles are associated with H pylori infection.

PMID- 17009403
TI  - Resistance to activated protein C is a risk factor for fibrostenosis in Crohn's
      disease.
AB  - AIM: To evaluate the effect of resistance to activated protein C (aPCR), the most
      common known inherited thrombophilic disorder, on the risk of intestinal
      operation of fibrostenosis in patients with Crohn's disease (CD). METHODS: In a
      previous study, we assessed the prevalence of aPCR in CD. In a retrospective case
      controlled study, 8 of these CD patients with aPCR were now compared with 24 CD
      patients without aPCR, matched by gender, age at diagnosis and duration of
      disease in a 1:3 fashion. The primary end point was the occurrence of an
      intestinal CD-related operation with evidence of fibrostenosis in the bowel
      resection specimen. RESULTS: The Kaplan-Meier analysis revealed that patients
      with aPCR had a lower probability of remaining free of operation with
      fibrostenosis than patients without aPCR (P = 0.0372; exact log-rank test)
      resulting in a significantly shorter median time interval from diagnosis of CD to
      the first operation with fibrostenosis (32 vs 160 mo). At 10 years, the
      likelihood of remaining free of operation with fibrostenosis was 25% for patients
      with aPCR and 57.8% for patients without aPCR. CONCLUSION: CD patients with aPCR
      are at higher risk to undergo intestinal operation of fibrostenosis than those
      without aPCR. This supports our hypothesis of aPCR being a possible risk factor
      for fibrostenosis in CD.

PMID- 17009404
TI  - Xeroderma pigmentosum group D 751 polymorphism as a predictive factor in resected
      gastric cancer treated with chemo-radiotherapy.
AB  - AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD)
      codon 751 variant with outcome after chemo-radiotherapy in patients with resected
      gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln
      polymorphisms in 44 patients with stage III (48%) and IV (20%) gastric cancer
      treated with surgery following radiation therapy plus 5-fluorouracil/leucovorin
      based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of
      relapse patients showed Lys/Lys genotype more frequently (P = 0.042). The Lys
      polymorphism was an independent predictor of high-risk relapse-free survival from
      Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P =
      0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important
      marker in the prediction of clinical outcome to chemo-radiotherapy in resected
      gastric cancer patients.

PMID- 17009405
TI  - Perinatal events and the risk of developing primary sclerosing cholangitis.
AB  - AIM: To investigate whether perinatal events, intrauterine or postpartum, are
      associated with the development of primary sclerosing cholangitis (PSC) later in
      life. METHODS: Birth records from 97 patients with adult PSC in Sweden were
      reviewed. Information on perinatal events including medications and complications
      during pregnancy, gestation length, birth weight and length were collected. Two
      control children of the same sex were selected for each subject. Conditional
      multiple logistic regression was used to assess associations of the perinatal
      measures with development of PSC. RESULTS: No significant associations were found
      between gestational age, birth length, breastfeeding, and the majority of medical
      complications including infections or medication during pregnancy for the mothers
      or postpartum for the children. Vaginal bleeding and peripheral oedema showed
      associations with PSC, with matched odds ratios of 5.70 (95% CI, 1.13-28.83) and
      2.28 (95% CI, 1.04-5.03), respectively. CONCLUSION: The associations of vaginal
      bleeding and oedema with subsequent PSC cannot readily be explained, so our
      findings do not strongly support the hypothesis of a significant role of
      perinatal events as a risk for the development of PSC later in life.

PMID- 17009406
TI  - Loss of disabled-2 expression is an early event in esophageal squamous
      tumorigenesis.
AB  - AIM: Disabled-2 (DAB2) is a candidate tumor-suppressor gene identified in ovarian
      cancer that negatively influences mitogenic signal transduction of growth factors
      and blocks ras activity. In a recent study, we observed down-regulation of DAB2
      transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to
      determine the clinical significance of loss of DAB2 protein in esophageal
      tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene
      silencing may account for loss of the protein. METHODS: DAB2 expression was
      analyzed by immunohistochemistry in 50 primary esophageal squamous cell
      carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant
      esophageal tissues. To determine whether promoter hypermethylation contributes to
      loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was
      analyzed in DAB2 immuno-negative tumors using methylation-specific PCR. RESULTS:
      Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%)
      dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed
      from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer
      (P(trend) < 0.001). Promoter hypermethylation of DAB2 was observed in 2 of 10
      (20%) DAB2 immuno-negative ESCCs. CONCLUSION: Loss of DAB2 protein expression
      occurs in early pre-neoplastic stages of development of esophageal cancer and is
      sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in
      ESCCs suggests that epigenetic gene silencing is only one of the mechanisms
      causing loss of DAB2 expression in ESCCs.

PMID- 17009407
TI  - Inhibition of hepatitis B virus expression and replication by RNA interference in
      HepG2.2.15.
AB  - AIM: To observe the inhibition of hepatitis B virus replication and expression by
      transfecting vector-based small interference RNA (siRNA) pGenesil-HBV X targeting
      HBV X gene region into HepG2.2.15 cells. METHODS: pGenesil-HBV X was constructed
      and transfected into HepG2.2.15 cells via lipofection. HBV antigen secretion was
      determined 24, 48, and 72 h after transfection by time-resolved
      immunofluorometric assays (TRFIA). HBV replication was examined by fluorescence
      quantitative PCR, and the expression of cytoplasmic viral proteins was determined
      by immunohistochemistry. RESULTS: The secretion of HBsAg and HBeAg into the
      supernatant was found to be inhibited by 28.5% and 32.2% (P < 0.01), and by
      38.67% (P < 0.05) and 42.86% (P < 0.01) at 48 h and 72 h after pGenesil-HBV X
      transfection, respectively. Immunohistochemical staining for cytoplasmic HBsAg
      showed a similar decline in HepG2.2.15 cells 48 h after transfection. The number
      of HBV genomes within culture supernatants was also significantly decreased 48 h
      and 72 h post-transfection as quantified by fluorescence PCR (P < 0.05).
      CONCLUSION: In HepG2.2.15 cells, HBV replication and expression is inhibited by
      vector-based siRNA pGenesil-HBV X targeting the HBV X coding region.

PMID- 17009408
TI  - Expression of matrix metalloproteinase-1 and tissue inhibitor of
      metalloproteinase-1 in ulcerative colitis.
AB  - AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue
      inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with
      ulcerative colitis (UC). METHODS: Reverse transcription-polymerase chain reaction
      (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and
      TIMP-1 at both mRNA and protein levels in patients with UC and controls. The
      relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and
      the severity of clinical symptoms of the patients with UC were also analyzed.
      RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and
      inflamed colonic mucosa was significantly higher than that in the non-inflamed
      colonic mucosa (P < 0.001), but there was no statistically significant difference
      in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05).
      The mRNA expression of MMP-1 and TIMP-1 in ulcerated colonic mucosa of UC
      patients was increased by 80-fold and 2.2-fold, respectively when compared with
      the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and
      1.6-fold, respectively. Immunohistochemical analysis showed that among the
      ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the
      normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35%
      respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and
      75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the
      MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical
      symptoms (P <0.05). CONCLUSION: Excessive expression of MMP-1 in the diseased
      colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and
      ulceration in UC patients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/TIMP-1 mRNA
      ratio can be used as biomarkers to judge the severity of clinical symptoms in
      patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel
      treatment for patients with UC.

PMID- 17009410
TI  - Necrosis of a large hepatic tumor after hemorrhage and subsequent selective
      arterial embolization.
AB  - This case report describes a young female patient presenting with acute intra
      abdominal hemorrhage originating from a large tumor in the liver, most likely a
      hepatocellular adenoma. The bleeding was stopped by selective embolization of
      right hepatic artery branches. Subsequently, partial hepatectomy was performed
      after 6 mo. Macro- and microscopic examination showed complete necrosis and
      absence of tumorous tissue. The patient was discharged without complications, and
      subsequent follow-up until 22 mo after resection did not reveal any new lesions
      in the liver. This case emphasizes the significance of selective arterial
      embolization in the management of bleeding liver tumors and questions the need
      for (partial) hepatectomy after this procedure in selective cases.

PMID- 17009409
TI  - Genotype-dependent activation or repression of HBV enhancer II by transcription
      factor COUP-TF1.
AB  - AIM: To study the expression of HBV enhancer II by transcription factor COUP-TF1.
      METHODS: In order to study the regulation of HBV variants in the vicinity of the
      NRRE we cloned luciferase constructs containing the HBV enhancer II from variants
      and from HBV genotypes A and D and cotransfected them together with expression
      vectors for COUP-TF1 into HepG2 cells. RESULTS: Our findings show that enhancer
      II of HBV genotype A is also repressed by COUP-TF1. In contrast, two different
      enhancer II constructs of HBV genotype D were activated by COUP-TF1. The
      activation was independent of the NRRE because a natural variant with a deletion
      of nt 1763-1770 was still activated by COUP-TF1. CONCLUSION: Regulation of
      transcription of the HBV genome seems to differ among HBV genomes derived from
      different genotypes. These differences in transcriptional control among HBV
      genotypes may be the molecular basis for differences in the clinical course among
      HBV genotypes.

PMID- 17009412
TI  - Huge primitive neuroectodermal tumor of the pancreas: report of a case and review
      of the literature.
AB  - Primitive neuroectodermal tumor (PNET) of the pancreas is an extremely rare tumor
      that usually occurs in children or young adults. We report a case of a 33-year
      old male patient with an 18 cm multiply 18 cm multiply 16 cm mass arising from
      the pancreatic body and tail with a one-day history of abdominal pain. Initial CT
      scan showed no signs of metastatic tumor spread. The tumor caused intrabdominal
      bleeding and the patient underwent primary tumor resection including partial
      gastrectomy, left pancreatic resection and splenectomy. Diagnosis of PNET was
      confirmed by histology, immunohistochemistry and FISH analysis. All neoplastic
      cells were stained positive for MIC2-protein (CD99). Approximately one month
      after surgery, several liver metastases were observed and the patient underwent
      chemotherapy according to the Euro-Ewing protocol. Subsequent relaparotomy
      excluded any residual hepatic or extrahepatic abdominal metastases. Although PNET
      in the pancreas is an extremely rare entity, it should be considered in the
      differential diagnosis of pancreatic masses, especially in young patients. This
      alarming case particularly illustrates that PNET in the pancreas although in an
      advanced stage can present with only a short history of mild symptoms.

PMID- 17009411
TI  - Biliary cystadenoma with mesenchymal stroma: report of a case and review of the
      literature.
AB  - Biliary cystadenomas are rare, cystic neoplasms of the biliary ductal system that
      usually occur in middle-aged women. They cannot be safely differentiated from
      cystadenocarcinomas before operation and should always be considered for
      resection. Cystadenomas have a strong tendency to recur, particularly following
      incomplete excision, and a potential of malignant transformation. Therefore,
      complete resection is the therapy of choice and thorough histopathologic
      evaluation is imperative. A case of benign biliary cystadenoma with mesenchymal
      stroma is presented along with a review of the relative literature addressing the
      clinical presentation, histology, histogenesis, differential diagnosis, imaging
      features, treatment and prognosis of this interesting and rare entity.

PMID- 17009413
TI  - Intracolonic multiple pebbles in young adults: radiographic imaging and
      conventional approach to a case.
AB  - Most of the foreign bodies detected in adult gastrointestinal systems are
      accidentally swallowed pins. In this study, we presented a case with intracolonic
      multiple pebbles. A 20-year-old man was admitted to emergency surgery policlinic
      for abdominal pain for 2 d without any alleviation or aggravation. His upright
      plain abdominal radiographic imaging revealed about 30-40 overt dense opacities
      in lumen of colonic segments, with oval and well shaped contours, each
      approximately 1 cm multiply 1 cm in size. The multiplanar reconstructions and
      three-dimensional images combined with sectional screening showed that all
      pebbles had passed completely into the colon and no foreign bodies had remained
      in the ileal segments. On psychiatric assessment, he was found to have immature
      personality features, difficulty in overcoming stressors and adaptation disorder.
      He recovered by conservative management and radiographic monitoring applied
      during his follow-up. Thus, it can be concluded that, in differential diagnosis
      of abdominal pain in adult ages, though less frequently seen than in children,
      gastrointestinal system foreign bodies should always be kept in mind and it
      should be considered that ingestion of pebbles may be one of the factors
      contributing to abdominal pain particularly in young adults with psychiatric
      problems. In such cases suspected of having foreign bodies which cannot be
      detected by plain films, abdominal tomography can be an alternative for
      diagnostic imaging.

PMID- 17009414
TI  - Sigmoid colonic carcinoma associated with deposited ova of Schistosoma japonicum:
      a case report.
AB  - We report a case of sigmoid colonic carcinoma associated with deposited ova of
      Schistosoma japonicum. A 57-year old woman presented with a 10-mo history of left
      lower quadrant abdominal pain and a 2-mo history of bloody stools. She had a
      significant past medical history of asymptomatic schistosomiasis japonica and
      constipation. A colonoscopy showed an exophytic fragile neoplasm with an
      ulcerating surface in the sigmoid colon. During the radical operative procedure,
      we noted the partially encircling tumor was located in the distal sigmoid colon,
      and extended into the serosa. Succeeding pathological analysis demonstrated the
      diagnosis of sigmoid colonic ulcerative tubular adenocarcinoma, and showed
      deposited ova of Schistosoma japonicum in both tumor lesions and mesenteric lymph
      nodes. Three days after surgery the patient returned to the normal bowel function
      with one defecation per day. These findings reveal that deposited schistosome ova
      play a possible role in the carcinogenesis of colorectal cancer.

PMID- 17009415
TI  - [Scents and chemical sensitivity, is it imagination?].

PMID- 17009416
TI  - [Home Chlamydia testing--what to believe?].

PMID- 17009417
TI  - [Cervix cancer screening failure in the county of Funen in spite of 25-year
      experiences].

PMID- 17009418
TI  - [Future physicians].

PMID- 17009419
TI  - [HIV therapy in poor countries].

PMID- 17009420
TI  - [Physicians should learn more about the mouth and the teeth].

PMID- 17009421
TI  - Analysis of tandem repeats found in 44 prokaryotic genomes.
AB  - Genomes contain various types of repetitive sequences. They may be used as probes
      for seeking genome rearrangements because they are rather free from the natural
      selection if they are located in the intergenic regions. In this study, we
      searched for tandem repeats (TRs) in 44 prokaryotic genomes by the color-coding
      method and sought the signs of genome rearrangements by detailed analysis of the
      detected TRs. We found 13,542 tandem repeats from 44 prokaryotic genomes in total
      ranging from several tens to one thousand per genome. The results of statistical
      analysis show that TRs tend to exist on high base composition bias regions in
      some genomes. Moreover, we recognized the characteristic distribution patterns of
      equivalent TR-pairs in 12 genomes, which are expected to indicate the occurrence
      of whole-genome duplication (WGD) on the genomes. It is demonstrated that TRs
      could indeed be used for seeking genome rearrangements. Although it has not been
      made clear at this time whether or not WGD had occurred in prokaryotic genomes,
      the results of the analyses of equivalent TR-pairs in this study are thought to
      be evidences of WGD in these genomes.

PMID- 17009422
TI  - Liver hydatid disease: radiofrequency-assisted  pericystectomy.

PMID- 17009423
TI  - One-handed KTP laser application with suction,  for ear surgery.

PMID- 17009424
TI  - A model for developing psychomotor skills in  arthroscopic knot tying.

PMID- 17009425
TI  - X-ray detectable thread for orientating a  breast specimen--an affordable and
      less  cumbersome solution.

PMID- 17009426
TI  - An innovation for conventional haemorrhoidectomy.

PMID- 17009427
TI  - Closed fracture manipulation--improving Charnley's three point fixation
      technique.

PMID- 17009428
TI  - An effective and easy method of splitting  damp Plaster of Paris casts.

PMID- 17009429
TI  - Parasitic diseases in Brazil: The Construction of Parasitology, XIXth - XXth
      Centuries. Proceedings of a conference, Paris, France, 3-5 February 2005.

PMID- 17009430
TI  - Proceedings of the XL Anniversary of Clinical Parasitology Day, Lodz, September
      8, 2001.

PMID- 17009431
TI  - Impact of measles control activities in the WHO African Region, 1999-2005.

PMID- 17009432
TI  - What if it's (sort of) a boy and (sort of ) a girl?

PMID- 17009433
TI  - Warfarin prevents more strokes than clopidogrel and aspirin in afib.
AB  - Warfarin is superior to the combination of clopidogrel (Plavix) plus aspirin in
      preventing strokes and systemic emboli in high-end patients with atrial
      fibrillation.

PMID- 17009434
TI  - Optimal algorithm for evaluating suspected DVT.
AB  - The most cost-effective algorithm for managing patients with suspected DVT was
      identified, though several are nearly as good. The main message is that the best
      approach uses a combination of a validated clinical decision rule, D-dimer test,
      and venous ultrasound.

PMID- 17009436
TI  - Intercourse doesn't hasten onset of labor.
AB  - Sexual intercourse at term pregnancy is not associated with earlier delivery. In
      this cohort, the mean gestational age at delivery was actually a few days older.
      We can throw out the common belief that intercourse hastens the onset of labor
      and delivery.

PMID- 17009435
TI  - Corticosteroids benefit patients with moderate to severe COPD.
AB  - Inhaled corticosteroids prevent exacerbations in patients with moderate to severe
      COPD. The benefit is minor, however, and steroids don't prevent exacerbations in
      patients with mild COPD. The prevention of exacerbations with steroids must be
      balanced against the higher rate of fractures and glaucoma.

PMID- 17009437
TI  - [Proceedings of the International Colloquium on Congenital Trypanosoma Cruzi
      Infection, Cochabamba, Bolivia, 6-8 November 2002].

PMID- 17009438
TI  - Abstracts of the 31st Scandinavian Congress of Rheumatology, Reykjavik, Iceland,
      August 16-19, 2006.

PMID- 17009439
TI  - Abstracts of the XIII Biennial Meeting of the Society for Free Radical Research
      International, August 15-19, 2006, Davos, Switzerland.

PMID- 17009440
TI  - Abstracts of the 12th Biennial Canadian Neuro-Oncology Meeting, May 26-28, 2006,
      Winnipeg, Canada.

PMID- 17009441
TI  - Abstracts of the 25th Congress of the International Association for Breast Cancer
      Research, Montreal, Quebec, 15-18 September 2006.

PMID- 17009442
TI  - Progress in small animal therapeutics (1953-2006).

PMID- 17009443
TI  - Understanding rabbits.

PMID- 17009444
TI  - Proceedings of the 3rd Asian Research Symposium in Rhinology, Nagoya, Japan, 29
      August 1998.

PMID- 17009445
TI  - Abstracts of the XXVI Congress of the European Association of Veterinary
      Anatomists, Messina, Italy, 19-22 July 2006.

PMID- 17009446
TI  - Settling all scores ... UHHS to pay $14 million in kickback lawsuit.

PMID- 17009447
TI  - Settling all scores ... and opening the market. Kansas IPAs settle FTC price
      fixing case.

PMID- 17009448
TI  - Modelling infectious diseases: viral complexity.

PMID- 17009449
TI  - Case studies in advanced monitoring: OptiVol.
AB  - Two cases of congestive heart failure with decompensation are presented. The
      OptiVol fluid index (Medtronic, Inc., Minneapolis, MN) provides an objective
      gauge of fluid status that can be difficult to obtain with routine clinical
      history or even with physical examination. The Cardiac Compass Report (Medtronic,
      Inc.) can identify a patient's ability to achieve euvolemia and the need for
      pharmacologic and nonpharmacologic interventions. Future studies will help define
      diagnostic and management algorithms using the OptiVol index, as well as in
      combination with other parameters in the Cardiac Compass Report, to facilitate
      proactive monitoring of patients with congestive heart failure.

PMID- 17009450
TI  - Discovery of indium complexes as water-tolerant Lewis acids.
AB  - The work on development of organic reactions that are tolerant to air and
      moisture, especially that of carbon-carbon bond forming reactions, had only
      started in the early 1990s. Our laboratory had approached this subject when it
      was still in its infancy and had developed methodologies for that end. In this
      article, our decade of work on indium complexes as Lewis acids is summarised.

PMID- 17009451
TI  - A facile synthesis of linear benzene-fused bis(tetrathiafulvalene) compounds and
      their application for organic field-effect transistors.
AB  - Three new linear benzene-fused bis(tetrathiafulvalene) compounds (1-3) were
      easily synthesized by one-step phosphite-induced cross-coupling reactions; a
      solution processed organic field-effect transistor based on 2 shows high mobility
      of 0.02 cm2/Vs.

PMID- 17009452
TI  - UV-manipulated wettability between superhydrophobicity and superhydrophilicity on
      a transparent and conductive SnO2 nanorod film.
AB  - A smart surface with wettability that can be switched between superhydrophobicity
      and superhydrophilicity has been realized on a transparent and conductive SnO2
      nanorod film by the alternation of UV-irradiation and dark storage.

PMID- 17009453
TI  - Isotactic N-alkyl acrylamide oligomers assume self-assembled sheet structure:
      first unequivocal evidence from crystal structures.
AB  - Herein we present the first unequivocal evidence of the ability of isotactic N
      alkyl acrylamide oligomers to assume self-assembled sheet-like structures that
      are reminiscent of protein beta-sheets.

PMID- 17009454
TI  - Vapor phase inclusion of ferrocene and its derivative in a microporous metal
      organic porous material and its structural characterization by single crystal X
      ray diffraction.
AB  - The inclusion of ferrocene and its derivative in metal-organic porous material
      MOF-5 is achieved by vapor diffusion; single-crystal X-ray diffraction studies
      using synchrotron radiation of ferrocene-loaded MOF-5 reveal well-ordered guest
      molecules packed into the pores.

PMID- 17009455
TI  - Sulfate anion helices formed by the assistance of a flip-flop water chain.
AB  - A flip-flop extended water structure assists the formation of sulfate anion
      helices (both left- and right-handed) in a crystalline hydrate of a simple
      organic-inorganic compound [C6H10N2]SO4. 1.5H2O (1).

PMID- 17009456
TI  - Magnetic separation of polymer hybrid iron oxide nanoparticles triggered by
      temperature.
AB  - The water dispersion of poly-N-isopropylacrylamide hybrid nanoparticles exhibited
      temperature-triggered magnetic separation behaviour: if the temperature switched
      between below and above 32 degrees C, the nanoparticles could be dispersed into
      water and reversibly separated by a magnetic field of 1.1 T.

PMID- 17009457
TI  - Insertion of two pyrene moieties into oligodeoxyribonucleotides for the efficient
      detection of deletion polymorphisms.
AB  - For the detection of deletion polymorphisms, two pyrene moieties are tethered to
      an oligodeoxyribonucleotide (ODN) on both sides of the intervening base; one- and
      two-base deletions can be selectively detected by the strength of the excimer
      emission.

PMID- 17009458
TI  - Mechanistic investigation on the hydrogenation of imines by[p
      (Me2CH)C6H4Me]RuH(NH2CHPhCHPhNSO2C6H4-p-CH3). Experimental support for an ionic
      pathway.
AB  - The need for acidic activation in the stoichiometric hydrogenation of benzyl-[1
      phenyl-ethylidene]-amine (6a) or [1-(4-methoxy-phenyl)-ethylidene]-methyl-amine
      (6b) by Noyori's catalyst [p-Me2CH)C6H4Me]RuH(NH2CHPhCHPhNSO2C6H4-p-CH3) (2) is
      inconsistent with the proposed concerted mechanism and supports an ionic
      mechanism.

PMID- 17009459
TI  - Synthesis of well-defined hydrogel networks using click chemistry.
AB  - New PEG-based hydrogel materials have been synthesized by Click chemistry and
      shown to result in well-defined networks having significantly improved mechanical
      properties; the selectivity of the azide/acetylene coupling reaction also allows
      for the incorporation of various additives and functional groups leading to
      chemical tailoring of the hydrogels.

PMID- 17009460
TI  - Spontaneous resolution of silver double helicates consisting of achiral ligands
      with several aromatic rings.
AB  - Symmetric breaking of silver double helicates through spontaneous crystallization
      was achieved via incorporation of C-H...pi and pi-pi stacking interactions of
      achiral ligands consisting of several aromatic rings.

PMID- 17009461
TI  - Fluoride-assisted synthesis of mullite (Al5.65Si0.35O9.175) nanowires.
AB  - Novel silicon-deficient mullite (Al5.65Si0.35O9.175) single crystal nanowires
      were synthesized in large quantities on mica substrates assisted by the
      intermediate fluoride species. The nanowires have diameters in the range 50-100
      nm and typical lengths of several microm. Aligned nanowires were observed at the
      substrate edge. The nanowires have strong photoluminescence (PL) emission bands
      at 310, 397, 452 and 468 nm.

PMID- 17009462
TI  - Synthesis of hierarchically mesoporous anatase spheres and their application in
      lithium batteries.
AB  - Hierarchically mesoporous TiO2 (anatase) sub-micron spheres with uniform particle
      size exhibiting high Li storage capacity and good cycling performance have been
      successfully prepared in a large quantity by using TiO2-CdSO4 composite as
      intermediate.

PMID- 17009463
TI  - Pummerer fragmentation vs. pummerer rearrangement: a mechanistic analysis.
AB  - Depending upon the nature of the substituent at the beta-position of the
      sulfoxide moiety, a Pummerer reaction can be oriented "at will" towards Calpha-H
      (rearrangement) or Calpha-Cbeta (fragmentation) bond cleavage.

PMID- 17009464
TI  - Hydrocarboxylation of terminal alkenes in supercritical carbon dioxide using
      perfluorinated surfactants.
AB  - High selectivity in acids is obtained in the first example of hydrocarboxylation
      of 1-octene in supercritical carbon dioxide using a Pd/P(4-C6H4-CF3)3 catalyst
      system and a perfluorinated surfactant.

PMID- 17009465
TI  - Novel organic dyes for efficient dye-sensitized solar cells.
AB  - Two novel metal-free organic dyes containing thienothiophene and thiophene
      segments have been synthesized. Nano-crystalline TiO2 dye-sensitized solar cells
      were fabricated using these dyes as light-harvesting sensitizers, and a high
      solar energy-to-electricity conversion efficiency of 6.23% was achieved.

PMID- 17009466
TI  - The first pamidronate containing polymer and copolymer.
AB  - Here we report the synthesis, characterization and hydrogelation of polymers
      consisting of pamidronate, a useful therapeutic agent.

PMID- 17009467
TI  - Organocatalysis "on water". Regioselective [3 + 2]-cycloaddition of nitrones and
      allenolates.
AB  - The first example of a regioselective and organocatalyzed 1,3-dipolar
      cycloaddition reaction between conjugated alkynoates and nitrones "on water" is
      described.

PMID- 17009468
TI  - Asymmetric aldol reactions catalyzed by tryptophan in water.
AB  - Tryptophan was shown to be able to catalyze direct aldol reactions between
      various cyclic ketones and aromatic aldehydes in water with high
      enantioselectivity.

PMID- 17009469
TI  - Synthesis of a coumarin compound from phenanthrene by a TiO2-photocatalyzed
      reaction.
AB  - Phenanthrene was converted into a coumarin compound by a TiO2-photocatalyzed
      reaction in an acetonitrile solution containing 8 wt% water and molecular oxygen
      in 45% yield.

PMID- 17009471
TI  - Phosphorus-carbon bond formation catalysed by electrophilic N-heterocyclic
      phosphines.
AB  - A P-chloro-diazaphospholene catalyses the phosphorus-carbon bond formation
      reaction between diphenylsilylphosphine and various alkyl chlorides.

PMID- 17009470
TI  - Vanadium (V) is reduced by the 'as isolated' nitrogenase Fe-protein at neutral
      pH.
AB  - Orthovanadate has been investigated in the presence of the nitrogenase Fe
      protein. Electron paramagnetic resonance (EPR) spectra demonstrate that vanadium
      (V) is reduced by the reduced Fe-protein to vanadium (IV) which then probably
      binds to the nucleotide binding site in place of the Mg2+ which is normally
      present. In contrast, the oxidized Fe-protein is unable to reduce vanadate. In
      this case vanadate has potential for use as a phosphate analogue where it acts as
      transition state mimic for hydrolysis.

PMID- 17009472
TI  - Nickel catalyzed stereoselective conjugate addition of dimethylzinc upon
      aldimines across 1,3-dien-8-ynes and 1,3-dien-9-ynes.
AB  - Ni(acac)2 catalyzes the five-component connection reaction of Me2Zn, alkynes,
      diene (of 1,3-dien-8-ynes and 1,3-dien-9-ynes), aldehydes and anisidine to
      furnish cyclic dienyl amines anti-2 with high remote 1,5-diastereoselectivity.

PMID- 17009473
TI  - Smart oligopeptide gels: in situ formation and stabilization of gold and silver
      nanoparticles within supramolecular organogel networks.
AB  - Tripeptide with redox active chemical entities based smart organogels have been
      used for in situ formation and stabilization of gold and silver nanoparticles
      within the supramolecular gel networks and the gold nanoparticles are aligned in
      arrays along the gel nanofibers of peptide 1-toluene gels.

PMID- 17009474
TI  - Redirecting the growth pattern with rapid maxillary expander and chin cup
      treatment: changing breathing pattern from oral to nasal.
AB  - AIM: This study was undertaken to assess the possibility of redirecting the
      growth pattern by using rapid maxillary expansion and a light-force chin cup for
      a short period of time, with limited patient cooperation, during the pre-growth
      and growth-spurt stages. METHODS: The study included a series of 60 patients, 24
      males and 36 females from 7 to 14 years of age, with crossbite or midfacial
      deficiencies. Treatment involved wearing a chin cup 24 hours a day to force mouth
      closure during rapid maxillary expansion activation, which was 2 turns per day to
      rapidly expand the midpalatal suture and enhance nasal breathing. Lateral
      cephalograms and intraoral and facial photographs were taken 2 years before
      treatment, at the time of rapid maxillary expansion, 3 weeks following rapid
      maxillary expansion activation, 3 months after the cessation of rapid maxillary
      expansion activation, and 1 to 3 years post-rapid maxillary expansion activation.
      RESULTS: Despite the severity, the crossbite would always improve within 21 days
      following rapid maxillary expansion activation. The cephalograms and photographs
      demonstrated forward movement of the nasal bridge and maxilla, with backward
      rotation of the mandible. The bite depth remained nearly the same as
      pretreatment. CONCLUSION: The results suggested that 24 hours of light-force chin
      cup wear, while expanding the midpalatal suture, is the major factor to force
      mouth closure and enhance nasal breathing. As a result, there is advancement of
      the maxilla, avoidance of tongue encroachment upon the mandible, and deceleration
      of horizontal mandibular growth.

PMID- 17009475
TI  - The correlation of sexual dimorphism in tooth size and arch form.
AB  - AIM: To determine the sexual dimorphism in the sizes of the 6 anterior teeth in
      the maxilla and the mandible, as well as the sexual dimorphism in the maxillary
      and mandibular arch forms in Greek patients seeking orthodontic treatment. An
      attempt was made to establish a correlation between tooth size and arch form.
      METHOD: The sample consisted of 100 male and 100 female patients seeking
      orthodontic treatment, between the ages of 20 and 25 years, and with no history
      of prior orthodontic treatment. Mesiodistal measurements of the 6 anterior teeth,
      as well as sagittal and transverse measurements of the dental arches, were taken
      on both the maxillary and mandibular casts. The subjects of the sample were
      divided into 5 groups, according to certain arch form characteristics determined
      from these measurements. RESULTS: The female subjects in this sample had both
      smaller teeth and smaller maxillary and mandibular arch dimensions. No
      significant differences in the distribution of the 5 forms according to gender
      were seen. When comparing the sum of the mesiodistal distances of the 6 anterior
      teeth to the arch form, the results do not offer a safe conclusion.

PMID- 17009476
TI  - Cephalometric evaluation of molar distalization by hyrax screw used in
      conjunction with a lip bumper.
AB  - AIM: To determine the treatment effects of the Hyrax screw, when used with a lip
      bumper appliance, on the distalization of maxillary molars and the reciprocal
      effects on the anchor premolars and maxillary incisors. METHODS: Records,
      including study casts, lateral cephalometric radiographs, extra- and intraoral
      photographs of 9 patients were taken at the start of treatment and after
      distalization was achieved. Wilcoxon signed rank test was performed to analyze
      the skeletal and dental changes. RESULTS: During the active period of maxillary
      molar distalization, the maxillary incisors significantly proclined by 5.89
      degrees (P <.05), 5.39 degrees (P <.05), and 1.72 mm (P <.05) relative to the SN,
      RH, and RV planes, respectively. The maxillary first molars showed significant
      distal crown tipping, as evidenced by 4.61-degree (P = .00), 4.17-mm (P = .00),
      and 1.11-mm (P = .02) decreases in U6-RH angle, U6 perpendicular RV, and U6
      perpendicular RH distances respectively. Anchorage loss, with 4.17 mm mesial
      movement of the maxillary second premolars, was significant (P = .01).
      CONCLUSION: When selecting the appropriate method for maxillary molar
      distalization, anchorage loss potential, the need for patient compliance, and the
      duration of treatment should be considered.

PMID- 17009477
TI  - Treatment of occlusal plane canting using miniscrew anchorage.
AB  - Two patient therapies introduce the use of miniscrew anchorage in adult patients
      for the correction of mild to moderate occlusal plane canting without severe
      facial asymmetries. A miniscrew implanted in the infrazygomatic buttress was used
      as anchorage for intruding the overerupted maxillary quadrant. As unilateral
      intrusion of maxillary posterior teeth will develop a posterior unilateral open
      bite, box elastics were subsequently used to extrude the opposing teeth in the
      mandibular arch. These treatments show that miniscrew anchorage offers a simple,
      efficient method of correcting occlusal plane canting and mild facial
      asymmetries.

PMID- 17009478
TI  - Analysis of the smile photograph.
AB  - Optimal facial esthetics is one of the objectives in orthodontic treatment and an
      important issue in modern society. In this context, orthodontic treatment permits
      individuals with dental malpositions to achieve improved dentofacial esthetics.
      To reach this result, the orthodontist needs to recognize the characteristics
      considered normal and pleasant in dental arches and smiles. The objective of this
      article is to review and discuss criterion adopted by dental literature to
      technically analyze the smile, such as dental midline, smile line, dental
      exposure, negative space, dental proportion, and symmetry. This article proposes
      a way to visualize an ideal smile for each patient.

PMID- 17009480
TI  - Case report: surgeon and orthodontist work together from patient's birth.
AB  - This case report presents one of the initial participants of a new treatment
      protocol started in 1965 for children born with complete clefts of the lip,
      alveolus, and palate at Children's Memorial Hospital, Chicago, USA. The surgeon
      and orthodontist worked together and in tandem from the time of the patient's
      birth. The protocol involves lip and palate closure, along with the placement of
      a passive maxillary prosthesis and minimal primary osteoplasty to the alveolus to
      help stabilize the maxillary segments. This case is noteworthy in that the
      patient had a number of congenitally missing teeth, and treatment required moving
      a tooth into and through an area originally cleft. The patient is now 40 years of
      age. Intra- and extraoral photographs, cephalometric radiographs, occlusal dental
      radiographs, and dental casts through the treatment stages are presented.

PMID- 17009479
TI  - Profile preferences of Korean American orthodontic patients and orthodontists.
AB  - AIM: The purpose of this study was to determine differences in preference for
      Korean American facial profiles among Korean American orthodontic patients with 2
      levels of acculturation, Asian American orthodontists, and Caucasian
      orthodontists. METHODS: Images of 1 male and 1 female Korean American adult were
      animated to move parts of the faces from an extreme retrusive position to an
      extreme protrusive position by using the Perceptometrics computer program. Three
      movies were created of the nose, lips, and chin for each image. Three groups of
      judges, ie, 18 Korean American orthodontic patients, 17 Asian orthodontists, and
      18 Caucasian orthodontists selected the most pleasing position and the zone of
      acceptability as a measure of tolerance. RESULTS: Statistically significant
      differences were found between Caucasian orthodontists and Korean American
      orthodontic patients for the most pleasing and midpoint of acceptability
      positions of female nose and male chin, with no differences in the zone of
      acceptability position among the groups. CONCLUSION: In general, the Korean
      American orthodontic patients preferred a more protrusive nose on the female
      image and more retrusive chin on the male image than Caucasian orthodontists for
      the most pleasing and midpoint of acceptability positions, with similar zone of
      acceptability for all 3 groups.

PMID- 17009481
TI  - A case of oculo-auriculo-vertebral spectrum with long-term and comprehensive
      management.
AB  - AIM: To show that a patient with severe oculo-auriculo-vertebral spectrum can
      achieve satisfactory occlusion and facial appearance through long-term and
      comprehensive management. METHODS: A patient, with oculo-auriculo-vertebral
      spectrum, had bilateral cleft lip and palate, macrostomia, malformed pinna, and
      unilateral hypoplasia of the zygomatic arch and mandible, which resulted in an
      asymmetric facial appearance characteristic of hemifacial microsomia. After
      bilateral lip repair and palatal closure, surgical repair of the pinna, nose, and
      cheiloplasty was performed. The patient was seen at the authors' dental hospital
      at 12 years 2 months of age. After lateral expansion of the maxillary arch, an
      edgewise multibracket appliance was placed and presurgical orthodontic treatment
      was begun. Combined maxillary and mandibular osteotomies were performed when the
      patient was 19 years of age, followed by genioplasty, multiple repair of the
      mandibular body and lip, and soft tissue transplantation to the left cheek, to
      improve facial symmetry. RESULTS AND CONCLUSION: After prosthetic treatment at 23
      years of age, a stable and functional occlusion with a satisfactory facial
      appearance was achieved.

PMID- 17009482
TI  - Single implant-supported crowns in the anterior maxilla--potential esthetic long
      term (> 5 years) problems.

PMID- 17009483
TI  - VIP interview: Birte Melsen. Interview by Samir E. Bishara.

PMID- 17009484
TI  - Phase-dependent effects of spinal cord stimulation on locomotor activity.
AB  - This paper examines how electrical stimulation of the spinal cord can modulate
      the output of the central pattern generator (CPG) for locomotion. Application of
      discrete current pulses to a single spinal segment was shown to affect multiple
      parameters of an ongoing locomotor pattern in an in vitro spinal cord. For any
      given stimulus, the effects on frequency, duration, and symmetry of locomotor
      output were strongly dependent on the phase at which stimulation was applied
      within the CPG cycle. Additionally, most stimuli had an immediate impact and
      evinced no effects on subsequent cycles. The most dramatic changes were seen when
      stimulation was applied during motor bursting: stimuli applied to the ipsilateral
      spinal hemicord increased the burst length, while stimuli applied to the
      contralateral spinal hemicord decreased the burst length. Smaller changes were
      observed when stimulating during delays between motor bursts. Thus, phasic
      stimulation was shown to influence the behavior of the CPG and spinal locomotion
      circuits on a cycle-by-cycle basis. This work represents the first step toward
      our ultimate goal of developing a neuroprosthetic device to restore locomotion
      after a severe spinal cord injury.

PMID- 17009485
TI  - Locomotor-related networks in the lumbosacral enlargement of the adult spinal
      cat: activation through intraspinal microstimulation.
AB  - It is commonly accepted that locomotor-related neuronal circuitry resides in the
      lumbosacral spinal cord. Pharmacological agents, epidural electrical stimulation,
      and sensory stimulation can be used to activate these instrinsic networks in in
      vitro neonatal rat and in vivo cat preparations. In this study, we investigated
      the use of low-level tonic intraspinal microstimulation (ISMS) as a means of
      activating spinal locomotor networks in adult cats with complete spinal
      transections. Trains of low-amplitude electrical pulses were delivered to the
      spinal cord via groups of fine microwires implanted in the ventral horns of the
      lumbosacral enlargement. In contrast to published reports, tonic ISMS applied
      through microwires in the caudal regions of the lumbosacral enlargement (L7-S1)
      was more effective in eliciting alternating movements in the hindlimbs than
      stimulation in the rostral regions. Possible mechanisms of action of tonic ISMS
      include depolarization of locally oscillating networks in the lumbosacral cord,
      backfiring of primary afferents, or activation of propriospinal neurons.

PMID- 17009486
TI  - Effects of neural refractoriness on spatio-temporal variability in spike
      initiations with Electrical stimulation.
AB  - In this paper, the effects of neural refractoriness on action potential (spike)
      initiations with electrical stimulation are investigated using computer modeling
      and simulation techniques. The computational model was composed of a myelinated
      nerve fiber with 50 nodes of Ranvier, each consisting of stochastic sodium and
      potassium channels, making it possible to represent the fluctuations of spike
      initiation. A series of two-pulse stimuli was presented by a stimulating
      electrode above the central (26th) node of Ranvier. The amplitude of the first
      (masker) pulse stimulus was set such that the masker pulse stimulus evoked spikes
      on each trial, while that of the second (probe) pulse stimulus was set such that
      the probe pulse stimulus evoked spikes on a half of trials, threshold values.
      Then the transmembrane potentials in response to the probe pulse stimulus were
      recorded at each node (i.e., 1-50 nodes) in order to determine the spike
      initiation node and time. From the observation of the spike initiation node and
      time, a spatio-temporal histogram as well as a spatial variability and a temporal
      variability of spike initiations was generated which allowed us to interpret
      fluctuations in spike initiation node and time. It was shown that the
      distribution of spike initiations tended to become greater spatially and longer
      temporally as the masker-probe intervals (MPIs) of the two-pulse stimuli
      shortened. It was also shown that the number of activated sodium channels as
      functions of space and time tended to become smaller due to inactivation of
      sodium channels and varied spatially and temporally as MPIs shortened. These
      findings may imply that the stochastic sodium channels during a relative
      refractory period may contribute to enhancing the fluctuations in spike
      initiations, and give us an insight into encoding information with electric
      stimuli to improve the performance of the prosthetic devices, especially cochlear
      implants.

PMID- 17009487
TI  - Two-dimensional variation of bursting properties in a silicon-neuron half-center
      oscillator.
AB  - We are developing hardware models of central pattern generators (CPGs) to enhance
      neural prostheses, create biologically based controllers for autonomous machines,
      and to better understand how biology creates stable and robust movements.
      Previously, we designed and implemented an analog integrated circuit model of a
      neuron with Hodgkin-Huxley like dynamics, the silicon neuron. In this work, we
      use silicon neurons to implement a half-center oscillator and show that the
      underlying dynamics of this CPG produce bursting behaviors that are well matched
      to the biological counterpart on which our model is based. In addition, we
      demonstrate the robustness of the bursting behavior by systematically varying two
      parameters in each silicon neuron and mapping the corresponding effects on the
      bursting.

PMID- 17009488
TI  - Electrical stimulation in isolated rabbit retina.
AB  - Experiments were conducted to assess the effect of stimulating electrode
      parameters (size, position, and waveform shape) on electrically elicited ganglion
      cell action potentials from isolated rabbit retina. Thirty-eight isolated rabbit
      retinas were stimulated with bipolar stimulating electrodes (either 125 or 25
      microm in diameter) positioned on either the ganglion or the photoreceptor side.
      Recording electrodes were placed between the optic disc and the stimulating
      electrodes. Cathodic-first, biphasic, current waveforms of varying pulse
      durations (0.1, 0.5, 1 ms) were used. For the four conditions tested (125
      electrode and 25-microm electrode, ganglion cell, and photoreceptor positions)
      threshold currents ranged from 6.7 to 23.6 microA, depending on location and
      pulse duration. With 1-ms pulse duration, no statistically significant difference
      was seen between threshold currents when either size electrode was used to
      stimulate either the ganglion cell side or the photoreceptor side. For all
      groups, the threshold currents using the 1-ms pulse were lower than those using
      0.1 ms, but the 0.1-ms pulses used less charge. These experiments provide a
      number of valuable insights into the relative effects of several stimulation
      parameters critical to the development of an implanted electronic retinal
      prosthesis.

PMID- 17009489
TI  - Utilizing gamma band to improve mental task based brain-computer interface
      design.
AB  - A common method for designing brain-computer Interface (BCI) is to use
      electroencephalogram (EEG) signals extracted during mental tasks. In these BCI
      designs, features from EEG such as power and asymmetry ratios from delta, theta,
      alpha, and beta bands have been used in classifying different mental tasks. In
      this paper, the performance of the mental task based BCI design is improved by
      using spectral power and asymmetry ratios from gamma (24-37 Hz) band in addition
      to the lower frequency bands. In the experimental study, EEG signals extracted
      during five mental tasks from four subjects were used. Elman neural network (ENN)
      trained by the resilient backpropagation algorithm was used to classify the power
      and asymmetry ratios from EEG into different combinations of two mental tasks.
      The results indicated that ((1) the classification performance and training time
      of the BCI design were improved through the use of additional gamma band
      features; (2) classification performances were nearly invariant to the number of
      ENN hidden units or feature extraction method.

PMID- 17009490
TI  - An experimental and theoretical framework for manufacturing prosthetic sockets
      for transtibial amputees.
AB  - Selective laser sintering (SLS) is a powerful manufacturing technology that does
      not require part-specific tooling or significant human intervention and provides
      the ability to easily generate parts with complex geometric designs. The present
      work focuses on developing a manufacturing framework using this technology to
      produce subject-specific transtibial amputee prosthetic sockets made of Duraform
      PA, which is a nylon-based material. The framework includes establishing an
      overall socket design (using the patellar-tendon bearing approach), performing a
      structural analysis using the finite element method (FEM) to ensure structural
      reliability during patient use, and validating the results by comparing the model
      output with experimental data. The validation included quantifying the failure
      conditions for the socket through a series of bending moment and compression
      tests. In the case study performed, the FEM results were within 3% of the
      experimental failure loads for the socket and were considered satisfactory.

PMID- 17009491
TI  - A novel mechatronic body weight support system.
AB  - A novel mechatronic body weight support (BWS) system has been developed to
      provide precise body weight unloading for patients with neurological or other
      impairments during treadmill training. The system is composed of a passive
      elastic spring element to take over the main unloading force and an active closed
      loop controlled electric drive to generate the exact desired force. Both force
      generating units, the passive spring and the active electric drive, act on the
      patient via a polyester rope connected to a harness worn by the patient. The
      length of the rope can be adjusted with an electric winch to adapt the system to
      different patient sizes. The system is fully computer controlled. At unloading
      loads of up to 60 kg and walking speeds of up to 3.2 km/h, the mean unloading
      error and the maximum unloading error of the presented BWS system was less than 1
      and 3 kg, respectively. The performance was compared with those of two purely
      passive BWS systems currently being used by most other rehabilitation groups.
      This comprised counterweight systems and static BWS systems with fixed rope
      lengths. Counterweight systems reached mean and maximum unloading errors of up to
      5.34 and 16.22 kg, respectively. The values for the static BWS were 11.02 kg and
      27.67 kg, respectively. The novel mechatronic BWS system presented in this study
      adjusts desired unloading changes of up to 20 kg within less than 100 ms. Thus,
      not only constant BWS, but also gait cycle dependent or time variant oscillations
      of the desired force can be realized with high accuracy. Precise and constant
      unloading force is believed to be an important prerequisite for BWS gait therapy,
      where it is important to generate physiologically correct segmental dynamics and
      ground reaction forces. Thus, the novel BWS system presented in this paper is an
      important contribution to maximize the therapeutic outcome of human gait
      rehabilitation.

PMID- 17009492
TI  - Partition between volitional and induced forces in electrically augmented dynamic
      isometric muscle contractions.
AB  - Augmentation of force in partially deficient muscles can be achieved by combining
      electrical stimulation (ES) with their volitional activation (hybrid activation).
      However, while the overall torque results from the combination of the volitional
      and the electrically-induced torque components, the exact share between these
      components is not known. In a previous work, we described a method to resolve the
      share between the torque components under isometric static contractions. In this
      work, we extend our analysis to the case of isometric dynamic contractions. Five
      healthy subjects were instructed to contract their Tibialis Anterior (TA) muscles
      according to a typical gait-like dynamic torque pattern, that was visually
      displayed to them, while monitoring their actual ankle torque and TA
      electromyography (EMG). These experiments were done with and without augmented
      activation by means of ES. A computational algorithm was developed to dissociate
      the volitional from the overall torque, based on EMG signal processing and on
      precalibration of the dynamic system of the volitional torque versus EMG. The
      results indicated the quantitative relations between decrease in the volitional
      torque and the required increase in ES enhancement. The developed method also
      demonstrated what ES intensity profile is necessary to produce a desired overall
      torque output. This provides the means for designing an adaptive rehabilitation
      device for the hybrid activation of deficient muscles.

PMID- 17009493
TI  - A three-dimensional finite element model of the transibial residual limb and
      prosthetic socket to predict skin temperatures.
AB  - Amputees who wear prosthetic limbs often experience discomfort from blisters and
      sores due to mechanical insult; these skin conditions are exacerbated by elevated
      skin temperatures and excessive perspiration within the prosthetic socket. The
      goal of this study was to create a tool for developing new prostheses that
      accommodate varying thermal loads arising from everyday activities. A three
      dimensional thermal model of a transtibial residual limb and prosthesis was
      constructed using the finite element (FE) method. Transverse computerized
      tomography (CT) scans were used to specify the geometry of the residual limb and
      socket. Thermal properties from the literature were assigned to both biological
      tissue and prosthetic socket elements. The purpose of this work was to create a
      model that would aid in testing the effect of new prosthesis designs on skin
      temperature. To validate its output, the model was used to predict the skin
      temperature distribution in a common prosthetic socket system (silicone liner,
      wool sock, and carbon fiber socket) at rest with no mechanical loading. Skin
      temperatures were generally elevated near muscle and decreased anteriorly and at
      the distal end. Experimental temperature measurements taken at the skin
      prosthesis interface of five human subjects were used to validate the model. Data
      extracted from the thermal model at anterior, posterior, lateral, and medial
      locations were typically within one standard deviation of experimental results;
      the mean temperatures were within 0.3 degree C for each section and were within
      0.1 degree C overall.

PMID- 17009494
TI  - Robotic personal aids for mobility and monitoring for the elderly.
AB  - Two rehabilitation devices, or personal aids for mobility and monitoring (PAMM),
      for use by the elderly are presented. The devices are intended to delay the
      transition from eldercare (assisted living) facilities to nursing homes. The
      robotic PAMMs provide support, guidance, and health monitoring. Two experimental
      systems are described: a cane and a walker. Issues of mobility, sensing, and
      control, as well as experimental data from trials in an assisted living facility
      using both systems are presented.

PMID- 17009495
TI  - Application of haptic interface for finger exercise.
AB  - A haptic device with two active degrees-of-freedom and a tendon-driven
      transmission system was designed, later on constructed, and submitted to testing.
      It was embodied as a lightweight mechanism with a small workspace that wraps the
      finger workspace and can generate forces up to 10 N suitable for finger exercise.
      The control loop and the user application were implemented on a personal computer
      in the Microsoft Windows environment. Along with the device, application covering
      several different experiment types was developed. The system was evaluated in a
      group of stroke patients during a one-month period of therapy. Results for two
      types of experiments are presented. The progress of the patient affected hand
      side was found to be greater than for the one nonaffected, however, the mean
      values of the relevant parameters on the nonaffected side of patients are higher
      than those for the affected side. Results were compared to the motor component of
      functional independence measure (M-FIM) measured clinical scale.

PMID- 17009496
TI  - Design and evaluation of a stance-control knee-ankle-foot orthosis knee joint.
AB  - Conventional knee-ankle-foot orthoses (KAFOs) are prescribed for people with knee
      extensor muscle weakness. However, the orthoses lock the knee in full extension
      and, therefore, do not permit a natural gait pattern. A new electromechanical
      stance-control knee-ankle-foot orthosis (SCKAFO) knee joint that employs a novel
      friction-based belt-clamping mechanism was designed to enable a more natural
      gait. The SCKAFO knee joint allows free knee motion during swing and other non
      weight-bearing activities and inhibits knee flexion while allowing knee extension
      during weight bearing. A prototype SCKAFO knee joint was mechanically tested to
      determine the moment at failure, loading behavior, and wear resistance. The mean
      maximum resisting moment of the SCKAFO knee joint over five loading trials was 69
      Nm +/- 4.9 Nm. The SCKAFO knee-joint strength and performance were sufficient to
      allow testing on a 90 kg subject at normal walking cadence. Proper function of
      the new electromechanical knee joint was verified in walking trials of an able
      bodied subject.

PMID- 17009497
TI  - Gait analysis of low-cost flexible-shank transtibial prostheses.
AB  - The latest lower-limb prosthetic designs have been incorporated with dynamic
      elastic response (DER) components to enhance prosthesis flexibility, which are
      suggested to be beneficial to gait. Although DER prosthetic. feet are preferred
      by most transtibial amputees and their benefits to gait are supported by some
      biomechanical studies, many are still utilizing the simple conventional solid
      ankle cushioned heel (SACH) designs because of the lower cost. The monolimb, a
      transtibial prosthesis with the socket and the shank molded from a single piece
      of thermoplastic material, perhaps is an alternative to DER feet for providing
      flexibility at the shank. In addition to shank flexibility, low cost and light
      weight are other characteristics of monolimbs. In spite of the potential
      benefits, little analysis has been done to examine the simple-structured monolimb
      prosthesis. The main aim of this study is to evaluate the gait and perception of
      unilateral transtibial amputees using a flexible elliptical-shank monolimb as
      compared to a thicker circular-shank monolimb and a conventional rigid-shank
      prosthesis. Results suggested that a properly designed monolimb may potentially
      offer similar functional advantages to the relatively expensive DER feet.

PMID- 17009498
TI  - Automating arm movement training following severe stroke: functional exercises
      with quantitative feedback in a gravity-reduced environment.
AB  - An important goal in rehabilitation engineering is to develop technology that
      allows individuals with severe motor impairment to practice arm movement without
      continuous supervision from a rehabilitation therapist. This paper describes the
      development of such a system, called Therapy WREX or ("T-WREX"). The system
      consists of an orthosis that assists in arm movement across a large workspace, a
      grip sensor that detects hand grip pressure, and software that simulates
      functional activities. The arm orthosis is an instrumented, adult-sized version
      of the Wilmington Robotic Exoskeleton (WREX), which is a five degrees-of-freedom
      mechanism that passively counterbalances the weight of the arm using elastic
      bands. After providing a detailed design description of T-WREX, this paper
      describes two pilot studies of the system's capabilities. The first study
      demonstrated that individuals with chronic stroke whose arm function is
      compromised in a normal gravity environment can perform reaching and drawing
      movements while using T-WREX. The second study demonstrated that exercising the
      affected arm of five people with chronic stroke with T-WREX over an eight week
      period improved unassisted movement ability (mean change in Fugl-Meyer score was
      5 points +/- 2 SD; mean change in range of motion of reaching was 10%, p <
      0.001). These results demonstrate the feasibility of automating upper-extremity
      rehabilitation therapy for people with severe stroke using passive gravity
      assistance, a grip sensor, and simple virtual reality software.

PMID- 17009499
TI  - Human adaptation to interaction forces in visuo-motor coordination.
AB  - We tested whether humans can learn to sense and compensate for interaction forces
      in contact tasks. Many tasks, such as use of hand tools, involve significant
      interaction forces between hand and environment. One control strategy would be to
      use high hand impedance to reduce sensitivity to these forces. But an alternative
      would be to learn feedback compensation for the extrinsic dynamics and associated
      interaction forces, with the potential for lower control effort. We observed
      subjects as they learned control of a ball-and-beam system, a visuo-motor task
      where the goal was to quickly position a ball rolling atop a rotating beam,
      through manual rotation of the beam alone. We devised a ball-and-beam apparatus
      that could be operated in a real mode, where a physical ball was present; or in a
      virtual training mode, where the ball's dynamics were simulated in real time. The
      apparatus presented the same visual feedback in all cases, and optionally
      produced haptic feedback of the interaction forces associated with the ball's
      motion. Two healthy adult subject groups, vision-only and vision-haptics (each n=
      10), both trained for 80 trials on the simulated system, and then were evaluated
      on the real system to test for skill transfer effects. If humans incorporate
      interaction forces in their learning, the vision-haptics group would be expected
      to exhibit a smoother transfer, as quantified by changes in completion time of a
      ball-positioning task. During training, both groups adapted well to the task,
      with reductions of 64%-70% in completion time. At skill transfer to the real
      system, the vision-only group had a significant 35% increase in completion time
      (p < 0.05). There was no significant change in the vision-haptics group,
      indicating that subjects had learned to compensate for interaction forces. These
      forces could potentially be incorporated in virtual environments to assist with
      motor training or rehabilitation.

PMID- 17009500
TI  - To be(long) or not to be(long): social identification in organizational contexts.
AB  - In the past few years, ideas of Social Identity Theory and Self-Categorization
      Theory have been successfully applied to the organizational domain. In this
      article, the authors provide an overview of these recent developments and present
      a concept of social identification in organizational contexts, based on these
      theories. The assumptions of this framework are that (a) social identification in
      organizational contexts is a multifaceted concept consisting of different
      dimensions and foci (or targets), (b) higher levels of identification are related
      to higher productivity and more positive work-related attitudes, and (c)
      identification is a very flexible concept that is linked to the situational
      context. The authors present the results of a series of field and laboratory
      studies in which the proposed relationships are analyzed and, in the main,
      confirmed.

PMID- 17009501
TI  - Modern prejudice toward gay men and lesbian women: assessing the viability of a
      measure of modern homonegative attitudes within an Irish context.
AB  - The authors examined the psychometric properties of the gay and lesbian versions
      of the Modern Homonegativity Scale (MHS-G and MHS-L) in samples of heterosexual
      Irish university students (Ns=179 and 353). Confirmatory factor analyses revealed
      that the MHS-G and MHS-L were unidimensional and factorially distinct from a well
      established measure of old-fashioned homonegativity (Attitudes Toward Lesbians
      and Gay Men Scale [ATLG]). Alpha coefficients for both versions of the MHS were
      good (range = .81 to .86), with 95% confidence intervals suggesting that
      unsatisfactory levels of scale score reliability (i.e., alpha values < .70) were
      relatively implausible. As hypothesized, participants' level of modern
      homonegativity correlated positively with their levels of old-fashioned and modem
      racism, patriotism, nationalism, religious fundamentalism, social dominance, and
      perceived political conservatism. The authors also observed a substantial inverse
      correlation between modern prejudice toward sexual minorities and support for
      their human rights. Finally, a series of multiple regression analyses indicated
      that, despite their interrelatedness, modern and old-fashioned homonegativity,
      particularly as they pertain to gay men, possess differential predictors.
      Limitations of the current series of studies and the need to conduct further
      research on attitudes toward sexual minorities within an Irish context are also
      discussed.

PMID- 17009502
TI  - Forming subjective representations of subjective representations: evidence of a
      subjective status bias.
AB  - In 3 studies and 2 pilot experiments, the author examined whether attending to
      the subjective status of mental representations would affect the ways humans view
      representational contents. The author found that simple drawing tasks were
      executed differently depending on whether or not the subject of the drawing was
      defined as a mental content (belief, imagination, perception). The results
      challenged particular lay epistemological concepts. They were partly accounted
      for by Gricean conversational rules (H. P. Grice, 1975), but the author
      postulated a subjective status bias to fully explain them. The discussion and
      recommendations for research center on the nature of this bias and relate it
      either to a tendency to conceive subjective representations as vague shadows of
      reality, or to an increased impact of the law of pregnance.

PMID- 17009503
TI  - Three-dimensional multislice helical computed tomography techniques for canine
      extra-hepatic portosystemic shunt assessment.
AB  - The purpose of the present study was to investigate the feasibility and
      usefulness of three-dimensional (3D) multislice computed tomography (CT)
      angiography with maximum intensity projection (MIP) and volume rendering (VR) in
      six dogs with clinical and sonographic findings suggestive of portosystemic
      shunt. Furthermore, we aimed to estimate the diameter of the portal vein and
      shunt vessels. MIP and VR reconstructions were performed for each patient and the
      origin and insertion of all shunt vessels were detected. In addition, 3D
      reconstructions allowed excellent depiction of vascular morphology and
      topography. All diagnoses and vessel measurements were confirmed by surgery. 3D
      multidetector CT angiography is a promising, noninvasive, and accurate method of
      evaluating dogs with suspected portosystemic shunts.

PMID- 17009504
TI  - Computed tomographic quantification of canine adrenal gland volume and
      attenuation.
AB  - We conducted a retrospective study in presumed normal dogs to determine the
      adrenal gland attenuation and volume values. Multidetector computer tomography
      (MDCT 16) analysis of the gland was carried out in 48 adult dogs without evidence
      of adrenal gland disease that underwent CT examination for acute spinal injuries.
      The mean nonenhanced attenuation value +/- SD of the left adrenal gland was 36.0
      +/- 5.3 HU (range: 22.0-42.0 HU). The mean nonenhanced attenuation value +/- SD
      of the right gland was 34.3 +/- 7.0 HU (range: 20.4-48.6HU). The mean enhanced
      attenuation value +/- SD were: left gland 101.5 +/- 10.6HU (range: 86.8-128.0
      HU), and right gland 97.4 +/- 12.4 HU (range: 58.9-123.6 HU). The mean CT volume
      +/- SD were: left gland was 0.60 cm3 (range: 0.20-0.95; SD 0.17), and right gland
      (0.55cm3, range: 0.22-1.01; SD 0.19). Attenuation values and volume data were
      related to age, weight, and gender, using ANOVA. There was no statistically
      significant difference between the left and right side or in adrenal
      measurements, because of body weight class effects. The animal effect was the
      most important source of variation for all adrenal measurements. Based on our
      study, CT is an effective method for assessing adrenal characteristics in the
      dog. Normative CT data are provided to allow estimation of normal adrenal gland
      size and volume.

PMID- 17009506
TI  - Anatomic and computed tomographic atlas of the head of the newborn bottlenose
      dolphin (Tursiops truncatus).
AB  - The head of a newborn dolphin (Tursiops truncatus), that died shortly after birth
      was imaged using computed tomography (CT). Gross cross-sectional slices of the
      head were compared with the CT images to identify normal structures of the
      cranium, brain, and respiratory and digestive pathways. Labelled transverse CT
      images of the dolphin head are presented sequentially as a reference for normal
      anatomy.

PMID- 17009505
TI  - Influence of patient positioning on the l5-l6 mid-laminar distance.
AB  - The aim of this project was to determine the effect of patient position on the L5
      L6 mid-laminar distance (MLD). The lumbar area of 22 recently euthanatized dogs
      of various breeds was radiographed in three positions: lateral recumbency with
      the spine in neutral position, lateral recumbency with the spine flexed in a
      kyphotic position, and sternal recumbency with the spine flexed in a kyphotic
      position. Digital images of the radiographs were analyzed using a computer
      program that allowed measurement of the MLD between L5-L6 in the three positions.
      The L5 and L6 MLD was significantly larger in sternal recumbency with the spine
      flexed (142.3 units) than both in lateral recumbency with the spine flexed (138.7
      units; P= 0.001) and lateral recumbency with the spine in the neutral position
      (135.8 units; P < or = 0.001). The MLD in lateral recumbency with the spine
      flexed was significantly larger than in lateral recumbency with the spine in
      neutral position (P = 0.005). Positioning a dog in sternal recumbency with the
      spine flexed produces a significantly larger MLD than in lateral recumbency with
      the spine flexed; this should simplify needle placement when performing a lumbar
      puncture.

PMID- 17009507
TI  - Magnetic resonance imaging appearance of the Cisterna chyli.
AB  - Thoracolumbar spinal magnetic resonance imaging (MRI) examinations in dogs
      frequently include the region of the cisterna chyli within the field of view. It
      is important to be aware of the appearance and location of this structure to
      avoid confusing it for a pathologic periaortic lesion. MRI examinations of the
      thoracolumbar spine were reviewed in 30 dogs. The cisterna chyli was identified
      in 26 dogs and was most commonly located caudal to the diaphragmatic crura at the
      level of L4; afferent and efferent lymphatics were seen in all dogs. Transverse
      T2-weighted images were the most useful to locate the cisterna chyli. It was
      isointense to fluid on T2-weighted images and isointense to muscle on T1-weighted
      images. Mild contrast enhancement was seen in three dogs. The cisterna always
      wrapped around the aorta, but varied in shape, with the most common being the
      wide right dorsolateral ellipse. The thoracic duct was also visible in 30 dogs.
      MRI may have potential for noninvasive evaluation of the abdominal and thoracic
      lymphatic ducts in dogs.

PMID- 17009508
TI  - Imaging diagnosis: congenital lobar emphysema in an old English sheepdog puppy.

PMID- 17009509
TI  - Imaging diagnosis: absence of the left external and both internal jugular veins
      in a cat.

PMID- 17009510
TI  - Characterization of severe small airway disease in a puppy using computed
      tomography.
AB  - A young Golden Retriever dog developed severe respiratory distress following an
      initial clinical diagnosis of infectious tracheobronchitis. Severe expiratory
      flow limitation, associated with exertional respiratory distress and hypoxemia
      was present. Thoracic images obtained with conventional radiography were
      characterized by hyperinflation and abnormal bronchial and alveolar patterns.
      Computed tomography was performed and in conjunction with pulmonary functional
      changes was diagnostic of small airway disease. The dog was treated with a
      variety of antibiotics, anti-inflammatory agents, and antitussives, but the
      clinical signs worsened and the puppy was euthanized. Pathologic examination
      confirmed severe small airway disease, with emphysema and bronchiolitis.

PMID- 17009511
TI  - Imaging diagnosis: penile hemangiosarcoma.

PMID- 17009512
TI  - Ultrasonography of the equine larynx.
AB  - Nasopharyngeal and laryngeal evaluation is important when examining horses with
      upper airway signs for poor performance. Currently endoscopy is the most common
      method to evaluate the equine upper airway. Ultrasonography of the equine larynx
      has not previously been described. Using six cadaveric specimens and four
      standing horses, the ultrasonographic appearance of the equine larynx was
      established. A scanning technique, including useful acoustic windows and the
      normal ultrasonographic appearance at each site, is described. Ultrasound allowed
      visualization of portions of the hyoid apparatus, laryngeal cartilages,
      associated soft tissues, and intrinsic and extrinsic laryngeal musculature, that
      are not seen using endoscopy. Additionally, real-time ultrasound allowed
      observation of the movement of the vocal folds and the arytenoid cartilages
      during respiration. In three horses with arytenoid chondritis, ultrasonography
      aided in the diagnosis and localization of arytenoid abcessation and
      perilaryngeal inflammation. The establishment of this technique will serve as the
      basis for future investigations in the evaluation of clinical patients with upper
      airway abnormalities.

PMID- 17009513
TI  - M-mode echocardiographic parameters and indices in the normal German shepherd
      dog.
AB  - M-mode echocardiographic measurements were made from 50 healthy German Shepherd
      dogs (30 males and 20 females). The dogs were awake and unsedated, in right
      lateral recumbent position. The following parameters were measured on the
      echocardiographic images: interventricular septal thickness at end-diastole
      (IVSd), interventricular septal thickness at end-systole (IVSs), left ventricular
      internal dimension at end-diastole (LVIDd), left ventricular internal dimension
      at end-systole (LVIDs), left ventricular posterior wall thickness at end-diastole
      (LVPWd), left ventricular posterior wall thickness at end-systole (LVPWs), left
      atrial dimension (LAD), aortic root dimension (AOD), left atrial to aortic root
      ratio (LAD/AOD), right ventricular internal dimension at end-diastole (RVID),
      amplitude of mitral valve excursion (DE amplitude), velocity of mitral valve
      opening (D-E slope), and velocity of mitral valve closure (E-F slope). Fractional
      shortening (FS) was also calculated. The effect of gender and age on each
      echocardiographic parameter was analyzed and the relationship between body weight
      (BW) and each parameter was also investigated. There was a significant
      relationship between gender and LVPW in systole and diastole and FS. Significant
      association was also found between BW and IVS, LVID, and LVPW in systole and
      diastole, FS, LAD, AOD, RVID, DE amplitude, and D-E slope of the mitral valve.

PMID- 17009514
TI  - The hilar perivenous hyperechoic triangle as a sign of acute splenic torsion in
      dogs.
AB  - Diagnosis of acute primary splenic torsion is challenging. The ultrasonographic
      appearance of this condition has been described, but other splenic diseases, such
      as diffuse infarction because of thrombosis, can appear very similar. We describe
      an additional ultrasonographic sign of acute splenic torsion; a triangular
      hyperechoic area at the hilus between the veins and the splenic parenchyma that
      is continuous with the hyperechoic mesentery. In a group of animals where acute
      splenic torsion was part of the ultrasound report differential diagnosis, we
      compared findings in dogs with torsion with findings in dogs with other splenic
      conditions. The presence of a hilar hyperechoic perivenous triangle was
      significantly associated with splenic torsion (P = 0.005). We speculate that this
      sign is associated with torsion because of the secondary severe, diffuse splenic
      enlargement. Although not pathognomonic, this sign could be used to more
      accurately diagnose splenic torsion in light of other findings consistent with
      this condition.

PMID- 17009515
TI  - Ultrasonographic and computed tomographic examinations of the avian eye:
      physiologic appearance, pathologic findings, and comparative biometric
      measurement.
AB  - Ultrasonography (US) and computed tomography (CT) were performed after routine
      ophthalmologic and ophthalmoscopic examinations in 190 eyes of six various
      diurnal (common buzzard [Buteo buteo L., 1758], n = 20; common kestrel
      [Tinnunculus tinnunculus L., 1758], n = 20) and nocturnal raptor species (barn
      owl [Tyto alba L., 1758], n = 22; tawny owl [Strix aluco L., 1758], n = 8; long
      eared owl [Asio otus L., 1758], n = 5; horned owl [Bubo bubo L., 1758], n = 1);
      and domestic pigeons (Columba livia, Gmel., 1789; n = 19), with a total of 95
      individuals. Pathologic findings such as lens subluxation and luxation,
      intravitreal hemorrhage, detached retina, post-traumatic partial sequestration,
      or malformation of the pecten could be demonstrated with diagnostic imaging
      tools, while opacities of cornea or lens constrained direct ophthalmoscopic
      examination. The results proved US to be a quick noninvasive imaging technique
      for detailed ocular diagnoses. CT provided detailed information of the bony skull
      and bony scleral rings as well as adequate visualization of shape, size, and
      margination of the eye and lens. Nevertheless, CT was unable to differentiate
      subtle structures within the vitreous like the pecten oculi or hemorrhage.
      Biometric measurements were carried out to objectify imaging results. Results
      showed good correlation of depth and width of the anterior eye chamber, lens and
      vitreous, length of the bulbus, and the pecten but no correlation of cornea and
      posterior wall thickness was found.

PMID- 17009516
TI  - Multimodality image fusion to facilitate anatomic localization of 99mTC
      pertechnetate uptake in the feline head.
AB  - 99mTc-pertechnetate is excreted in humans by the thyroid glands, gastric mucosa,
      salivary glands, choroid plexus, and sweat glands. Uptake attributed to the
      zygomatic and molar salivary glands is used commonly as a reference to assess
      thyroid uptake and differentiate euthyroid from hyperthyroid cats. However, the
      exact location and origin of uptake of 99mTc-pertechnetate in the head during
      thyroid scintigraphy in cats remains uncertain. The purpose of this study was to
      localize uptake of 99mTc-pertechnetate in the head of the cat using multimodality
      image fusion. Computed tomography (CT), magnetic resonance (MR), and single
      photon emission tomography (SPECT) imaging were performed successively in two
      cats during the same anesthesia procedure. Transverse, dorsal, and sagittal
      images were reconstructed for each modality. Images were rescaled and fused
      manually. The anatomic location of focal 99mTc activity in SPECT images was
      identified in CT and MR images. Four major and four minor focal areas of uptakes
      were identified in the head in both cats. A rostral conical-shaped activity was
      identified in the nasal cavity. Two symmetric focal areas of uptakes seen in the
      soft tissues in the ventro-caudal retro-bulbar region, and rostro-medial to the
      vertical ramus of the mandible were attributed to zygomatic salivary glands. A
      central focal activity located ventral and caudal to the zygomatic uptake was
      located in the nasopharynx and soft palate. Minor symmetric areas of uptake
      identified in the retromandibular region were attributed to parotid and
      mandibular salivary glands. Minor symmetric areas of uptake identified in the
      region of the mandible were attributed to molar salivary glands. No focal area of
      uptake was identified in the brain.

PMID- 17009517
TI  - Identifying removable radioactivity on the surface of cats during the first week
      after treatment with iodine 131.
AB  - Because radioiodine (1-131) is excreted in urine and saliva, treated cats can
      accumulate I-131 on their coats from contacting soiled litter and grooming. This
      could result in removable radioactivity, which is a potential source of human
      exposure to radiation and specifically to internal contamination. The purpose of
      this study was to determine if there is removable radioactivity on cats treated
      with I-131. Daily wipe tests were performed for 7 days at two sites (both flanks,
      one site; and all four paws, one site) on six hyperthyroid cats treated with I
      131. A y counter was used to determine the counts per minute (cpm) of the
      samples, which were converted to disintegrations per minute (dpm) to estimate
      activity. The results were compared to the New York State limits of removable
      activity for a non-controlled area (<1000dpm/100 cm2) to determine if the amount
      of removable activity was acceptable for a member of the public. The median value
      of removable activity was 241 dpm (range from 34 to 4184 dpm) for the flanks, and
      308 dpm (range from 60 to 1890 dpm) for the paws. The amount of removable
      radioactivity on the surface of hospitalized cats treated with I-131 during the
      first week after treatment, occasionally and without obvious pattern, exceeded
      the New York State limit. Sporadic activity as high as 4148 dpm was found. It is
      prudent to advise owners to observe routine hygiene when handling cats after
      discharge to minimize the risk of internal contamination.

PMID- 17009518
TI  - [CME radiology 15. Increased dyspnea during sports].

PMID- 17009519
TI  - [What is your diagnosis? Severe iron deficiency anemia manifestation after
      bariatric intervention].

PMID- 17009520
TI  - [Helicobacter pylori 2006: how to test, when to treat].
AB  - The role of Helicobacter pylori in peptic-disease, gastric adeno-carcinoma and
      the MALT- lymphoma is established. The H. pylori diagnostics and the eradication
      therapy are highly disputed in patients with dyspepsia. An endoscopy is
      recommended to patients older than 45 who have dyspeptic disorders. Non-invasive
      testing and treatment is an adequate option to those patients younger than 45, if
      no alarm symptoms exist. The H.pylori serology, the 13C- breath test and the
      stool-antigen test have proven to be the best in laboratory testing. The
      therapeutic regimen of H. pylori eradication consists of a proton pump inhibitor
      (PPI) and two antibiotics, though it isn't always successful. After a second
      treatment failure, a H. pylori culture is indicated to asses the antibiotic
      resistances.

PMID- 17009521
TI  - [Rare cases of intussusceptions in children].
AB  - Intussusception is common in children under two years of age. Most of them are
      idiopathic whereas intussusceptions secondary to focal pathologies are rare. We
      report of two unusual cases of ileocolic intussusception. In one child a mobile
      cecum was seen, in the second child a duplication cyst of the ileocecal valve.

PMID- 17009522
TI  - [Patient from Cameroon with recurrent, transient, itching swelling of arms and
      legs].

PMID- 17009523
TI  - [Male infertility update].
AB  - Exact etiological factors cannot be found in more than 70% of male infertility.
      Although the causes of some male infertility are known, the pathogenesis is not
      yet clear. Therefore, the diagnosis and treatment of male infertility are
      particularly complicated. Some breakthroughs have been made in the treatment of
      refractory male infertility since the development of ICSI in 1992. However,
      traditional treatment should also be taken into account for individual male
      infertility. The standardization of diagnosis and treatment and the improvement
      of the success rate and safety of assistant reproductive technology will be the
      dominant factors in the development of male infertility researches.

PMID- 17009524
TI  - [Di(2-ethylhexyl) phthalate affects the testes and leydig cells of neonatal KM
      mice].
AB  - OBJECTIVE: To explore the effects of di(2-ethylhexyl)phthalate (DEHP) on neonatal
      mice's testes and Leydig cells in vivo. METHODS: Pregnant mice were exposed to
      DEHP at the dose of 100 mg/kg, 200 mg/kg or 500 mg/kg (body weight) per day by
      gavage from gestation day 12 (GD 12) through postnatal day 3 (PND 3),
      respectively. The testis and body weights, testicular histopathology and the
      activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) of the neonatal mice
      were investigated. RESULTS: The body and testis weights of the male mice's
      offspring were significantly reduced following DEHP exposure. Leydig cell
      morphology was affected significantly by DEHP as compared with the controls.
      Leydig cells obviously increased in the neonatal mice's testes on PND 15 and PND
      30 when exposed to DEHP (500 mg/[kg x d]). Activities and positive area of the
      steroidogenic enzymes 3beta-HSD immunoexpression decreased markedly when exposed
      to DEHP (100 mg/[kg x d] or 200 mg/[kg x d]). Image analysis showed a decrease in
      the activities of 3beta-HSD in the animals exposed to DEHP (500 mg/[kg x d]), but
      an increase in the positive area of 3beta-HSD immunoexpression as compared with
      the control animals on PND 15 (P < 0.01). CONCLUSION: DEHP affects the Leydig
      cell morphology, the activity of 3beta-HSD, the testis and body weights and the
      testicular histopathology of neonatal mice, and it may function as an
      antiandrogenic agent.

PMID- 17009525
TI  - [Expression of human epididymis protein 2beta1 in the testis and epididymis of
      adolescent male rats].
AB  - OBJECTIVE: To investigate the expression of human epididymal secretary protein 2
      isoform human epididymal protein 2beta1(HE2beta1) in the testis and epididymis of
      adolescent male rats along with its significance. METHODS: Immunohistochemical
      staining was used to detect the expression and localization of HE2beta1 in the
      testis and epididymis of 15 adolescent SD rats. RESULTS: HE2beta1 immunoreactive
      staining was detected in the testis and epididymis. In the epithelia of the
      epididymal duct, HE2beta1 expressed mainly in the supranuclear region of the
      principle cells and the basement membrane of some epithelial cells; there were no
      immunostaining in the n clear cells, halo cells and basal cells. The
      immunopositive reaction was detected, weak in the distal caput, strong in the
      proximal, middle corpus and the cauda, but negative in the initial segment.
      Immunopositive results of HE2beta1 were also observed in some of the nuclei of
      spermatogonia and Sertoli cells with negatively-stained cytoplasm. CONCLUSION:
      Immunohistochemical staining is a fairly sensitive method for detecting HE2beta1
      expression. The localization and expression level of HE2beta1 in the genital duct
      of adolescent male rats exhibited a region- and cell-specific expression pattern,
      which suggests that HE2beta1 may play an important role in spermatogenesis,
      maturation and epididymal epithelial innate defense mechanisms.

PMID- 17009526
TI  - [Growth hormone enhances regeneration of cavernous nerves after their
      transplantation in rats].
AB  - OBJECTIVE: To investigate the effect of growth hormone (GH) on penile erection
      after reconstruction of cavernous nerves using sural nerve as an interposition
      nerve graft in rats. METHODS: Twenty-four male Sprague-Dawley rats (3-4 ms of age
      and 300-400 g in weight) were randomly divided into 2 groups: nerve graft group
      and GH group, each electrostimulated to determine the erectile potency 2 and 4
      months after nerve graft (followed by hypodermic GH injection). The nNOS-positive
      nerve fibers in the corpora cavemosa were examined by streptavidin-peroxidase
      immunohistochemistry technique (SP method). Image analysis was used to calculate
      the area stained in pixel. RESULTS: Electrostimulation at 2 months produced
      31.25% of erections in the GH group but none in the grafted rats. There was a
      significant difference in the erection rate produced by electrostimulation
      between the two groups at 2 months (P < 0.05). The pixel of the expression of
      nNOS-positive nerve fibers in the GH group (38971 +/- 7692) was also greater than
      that of the graft group (16538 +/- 3179, P < 0.05). At 4 months, 43.75% of the
      graft group and 75% of the GH group produced erections upon electrostimulation,
      with no significant difference between the two groups (P > 0.05). The pixels of
      the expression of nNOS-positive nerve fibers were 79276 +/- 12,021 and 91348 +/-
      18965, respectively (P > 0.05). CONCLUSION: GH can accelerate the regeneration of
      cavernous nerves after bilateral nerve grafting, and GH administration may
      present a new physiological approach to the treatment of erectile dysfunction
      after radical pelvic surgery.

PMID- 17009527
TI  - [Effects of antibiotic and anti-inflammatory treatment on serum PSA and free PSA
      levels in patients with chronic prostatitis IIIA].
AB  - OBJECTIVE: To investigate the effect of antibiotics and a nonsteroidal anti
      inflammatory agent on the level of total prostate specific antigen (PSA) and free
      PSA ratio (F-PSAR) in patients with chronic prostatitis IIIA. METHODS: A total of
      228 outpatients diagnosed as with chronic prostatitis III A received 4-week
      antibiotic and anti-inflammatory treatment. The PSA level and F-PSAR were
      determined before and after the treatment, and the changes analyzed. RESULTS:
      Significant variations were observed in the median PSA concentrations (3.51
      microg/L and 2.75 microg/L) and F-PSAR (0.25% and 0.27%) 4 weeks after the
      treatment. Sixty-five of the patients (28.5%) presented with serum PSA greater
      than 4 ng/ml, the mean PSA decreased by 32.9%, from 6.24 microg/L before the
      treatment to 4.58 microg/L 4 weeks after the treatment (P < 0.05), and the serum
      PSA was normalized in 18 of the 65 patients (27.7%). The median variation of F
      PSAR (0.16% and 0.22%) was greater than that of PSA. The variation indexes
      obtained 4 weeks after the treatment showed no statistical difference from those
      observed 8 weeks after the treatment. CONCLUSION: Chronic prostatitis IIIA
      appears to contribute to increased serum PSA levels in some men. Antibiotic and
      anti-inflammatory treatment could significantly reduce the PSA level and increase
      F-PSAR.

PMID- 17009528
TI  - [Urokinase-type plasminogen activator and urokinase-type plasminogen activator
      receptor in the seminal plasma and sperm of fertile and oligoasthenozoospermia
      males].
AB  - OBJECTIVE: To find the difference between the levels of urokinase-type
      plasminogen activator (uPA) and urokinase-type plasminogen activator
      receptor(uPAR) in the seminal plasma and sperm of fertile and
      oligoasthenozoospermia men, and to understand their correlation with male
      fertility. METHODS: The levels of uPA in the seminal plasma and sperm of 22
      normospermic males and 44 oligoasthenozoospermia patients were measured by ELISA.
      RESULTS: (1) The average level of uPA in the seminal plasma and sperm of the
      normospermic group, ([4803.69 +/- 602.78] mU/L) and ([30.29 +/- 3.16] mU/10(6)
      sperm) were higher than those of the oligoasthenozoospermia group, ([4061.35 +/-
      736.23] mU/L), and ([20.51 +/- 4.2] mU/10(6) sperm) (P < 0.01). (2) The average
      level of uPAR in the sperm of the normospermic group ([12.97 +/- 3.11] mU/10(6)
      sperm) was significantly higher than that of the oligoasthenozoospermia group,
      ([6.09 +/- 1.45] mU/10(6) sperm) (P < 0.01). (3) The levels of uPA and uPAR in
      the sperm and the content of uPA in the seminal plasma were positively correlated
      with sperm motility and viability. CONCLUSION: Urokinase-type plasminogen
      activator is related with male fertility and the levels of uPA and uPAR vary in
      the seminal plasma and sperm of fertile and oligoasthenozoospermia males.

PMID- 17009530
TI  - [Characteristics of erectile dysfunction in old males with lacunar infarction].
AB  - OBJECTIVE: To investigate the characteristics of erectile dysfunction (ED) in old
      males with lacunar infarction. METHODS: A total of 38 old patients ages from 60
      to 70 years were involved. The questionnaire of international index of erectile
      function 5 (IIEF -5) was used to determine the status and severity of ED.
      According to the focus of infarction on MRI, the patients were divided into two
      groups, Group I with lacunar infarction and minor neurological deficits, and
      Group II with none. The total IIEF-5 scores were compared between the two groups
      and repeatedly evaluated six months after discharge. RESULTS: According to the
      total scores of IIEF-5, the prevalence of ED in Group II (95%) was higher, and
      the incidence of severe ED was significantly increased (60.0% vs. 44.4%, P <
      0.05) as compared with Group II. In both the two groups, severe ED was more often
      seen in diabetic patients. At six months after discharge, the total scores of
      IIEF-5 were significantly increased (11.2 +/- 3.2 vs. 15.6 +/- 2.2, P < 0.05).
      CONCLUSION: ED is significantly increased in old males with lacunar infarction,
      and it is more severe in diabetic patients. Post-stroke rehabilitation care helps
      to improve ED.

PMID- 17009529
TI  - [Construction of pGEX4T-1-Cox7a2 and expression, purification and identification
      of the recombinant protein].
AB  - OBJECTIVE: To clone and express Cox7a2, one mitochondrial respiratory chain
      related gene, and to identify its recombinant protein. METHODS: The coding region
      of Cox7a2 was amplified from primary cultured mouse Leydig cells by RT-PCR. The
      PCR product was cloned into pGEX4T-1 vector by BamH I and EcoR I sites, and
      confirmed by DNA sequencing. The recombinant fusion protein vector was
      transformed and expressed into BL21. The recombinant fusion protein was
      identified by Western blotting. RESULTS: The entire coding region of Cox7a2 was
      cloned and expressed. The fusion protein was identified by anti-GST monoclonal
      antibody using Western blotting. CONCLUSION: The cloning of Cox7a2 and the
      expression of the recombinant protein would help to study the detailed function
      of Cox7a2, one respiratory chain related and highly differently expressed gene in
      the tissues of aging testes.

PMID- 17009531
TI  - [An integrated method works well on varicocele].
AB  - OBJECTIVE: To assess an integrated method of operation + Chinese medicine +
      dexamethasone + vitamin E in treating varicocele. METHODS: Ninety-six patients
      with varicocele were randomly divided into two groups, the experimental group
      (Group A, n=47) treated with the integrated method, the control group (Group B,
      n=49) treated with Chinese medicine, dexamethasone and vitamin E. RESULTS: After
      the treatment, the sperm density and motility and pregnancy rate were higher (P <
      0.01 or P < 0.05) and the sperm deformity rate was lower in the experiment group
      than in the control (P < 0.05). CONCLUSION: The integrated method works better
      than either operation or Chinese medicine applied alone in the treatment of
      varicocele.

PMID- 17009532
TI  - [Evaluation of sperm mitochondrial function using Rh123/PI dual fluorescent
      staining].
AB  - OBJECTIVE: To investigate the feasibility and clinical significance of detecting
      sperm mitochondrial function by using Rh123/PI dual fluorescent staining and flow
      cytometry analysis, and to explore the relationship between the results of
      Rh123/PI dual fluorescent staining and seminal parameters. METHODS: Sixty-three
      semen samples were classified as normal (n=31) and abnormal (n=32) according to
      the World Health Organization guidelines. Rh123/PI dual fluorescent staining was
      then carried out to evaluate sperm mitochondrial function by flow cytometry
      analysis. RESULTS: Significant differences in Rh123+ PI-, Rh123- /PI+ and Rh123-
      /PI- were detected between the normal and abnormal semen samples (P < 0.05).
      There was a significant positive correlation between the Rh123+ PI- sperm and
      sperm motility and a significant inverse correlation between Rh123+ PI- and
      immotile sperm. But the Rh123- PI+ sperm showed a contrary relationship with
      Rh123+ PI-. A significant inverse correlation was also observed between the Rhl23
      /PI- sperm and sperm concentration in the abnormal group. CONCLUSION: Rh123/PI
      dual fluorescent staining and flow cytometry analysis can readily and quickly
      detect sperm mitochondrial function and be used to evaluate semen quality.

PMID- 17009533
TI  - [A clinical study of prostat combined with an antibiotic for chronic nonbacterial
      prostatitis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of Prostate in combination with an
      antibiotic for the treatment of chronic nonbacterial prostatitis. METHODS: A
      double-blind, parallel contrasted, multi-central method was applied in the study.
      After the Stamey test and expressed prostate secretion (EPS) examination, 160
      patients with prostatitis were recruited and randomized into a trial group (80
      cases with 1 case missing) and a control group (80 cases). In the trial group,
      the patients used the levofloxacin and Prostate during the first 4 weeks and
      Prostate only during the following 4 weeks. In the control group, the patients
      used the levofloxacin and placebo during the first 4 weeks, and placebo only
      during the following 4 weeks. Before and 4 and 8 weeks after the treatment, the
      patients were visited and evaluated by the national institute health-chronic
      prostatitis symptom index (NIH-CPSI), EPS, and asked about the side. RESULTS:
      After 4-week and 8-week treatment, the pain index dropped by 3.34 +/- 2.45 and
      4.06 +/- 3.03 in the trial group, and effects. 2.28 +/- 2.42 and 3.30 +/- 3.29 in
      the control; the voiding index dropped by 2.22 +/- 1.79 and 2.77 +/- 2.04 in the
      trial group, and 1.24 +/- 1.67 and 1.83 +/- 2.25 in the control respectively.
      There was significant difference between pre-treatment and post-treatment in both
      the two groups (P < 0.01), while the difference was not significant between 4
      week and 8-week post-treatment (P > 0.05). And there was significant difference
      between the two groups in the pain index and voiding index (P < 0.01), but not in
      the white blood cell count and lipid in the EPS (P > 0.05). No serious side
      effects were recorded, and the tolerance to Prostate and placebo showed no
      significant difference. CONCLUSION: Prostate in combination with an antibiotic
      can effectively relieve the pain and voiding symptoms and improve the life
      quality of the patients with nonbacterial prostatitis and well deserves to be
      recommended in clinical practice.

PMID- 17009534
TI  - [Factors affecting clinical application of sex therapy for erectile dysfunction].
AB  - OBJECTIVE: To discuss the factors that affect the clinical application of sex
      therapy for erectile dysfunction (ED). METHODS: Urological researchers
      recommended free sex therapy to ED patients and their partners in the outpatient
      department and studied the factors affecting the patients of Medicaid their
      partnersology, acceptance of sex therapy by interview and observation. RESULTS:
      Many patients refused sex therapy. Only 11 pairs of volunteers underwent it, of
      whom 5 pairs gave up halfway, 1 pair were stopped by the therapist due to the
      breakup of their marriage, and merely 5 pairs accomplished the whole course.
      Among the 5 pairs of quitters, 2 pairs thought of their problem as organic and
      turned to drug therapy, 1 pair withdrew because the patient's girlfriend broke up
      with him, 1 pair gave up because they lived in another city too far away from the
      clinic, and the other pair discontinued because they could not spare the time
      from their work. CONCLUSIONS: Many factors affect the clinical application of sex
      therapy for ED in China. Apart from the shortage of qualified professional sex
      therapists, some factors from the patients and their partners are at work, such
      as stress of work, lack of time, home location, education background,
      relationship between the patient and his partner, attitude to sex therapy, and so
      on.

PMID- 17009536
TI  - [Diagnostic value of urodynamic parameters multianalysis in the evaluation of
      bladder outlet obstruction resulting from benign prostatic hyperplasia].
AB  - OBJECTIVE: To construct a function model that can be used in the diagnosis
      bladder outlet obstruction (BOO) resulting from benign prostatic hyperplasia, and
      to develop a diagram allowing the judgement of bladder outlet for patients with
      different detrusor contractility, especially with impaired one. METHODS:
      Urodynamic and clinical data of 131 men were analyzed retrospectively. By
      Logistic analysis, a function model was constructed. Based on the model, a
      diagram allowing the evaluation of bladder outlet was drawn. The cutoff point for
      diagnosing BOO with the function model and the curve was confirmed by ROC curve
      analysis. RESULTS: The function model (BOOI) was obtained by the formula 5.03 x
      residual fraction + 0.04 x PdetatQmax - 0.20 x Qmax - 0.91 + alpha (alpha = 0 for
      those with low pressure-low flow on P-FS, alpha = 1.42 for high pressure-low
      flow, alpha = -7.30 for high pressure-high flow). The cutoff point for BOOI
      diagnosing BOO was 0.36. When validated, the sensitivity, specificity, positive
      predictive value, and negative predictive value were 85.7%, 91.7%, 96.0% and
      73.3% respectively. CONCLUSION: The BOOI, with an easy calculation mode, could
      predict the probability of BOO. The sensitivity and specificity of the criterion
      for the diagnosis of BOO were satisfactory. The curve we drew could help to
      differentiate the obstructed men with low pressure-low flow and thus benefit them
      by surgical relief of their obstruction.

PMID- 17009535
TI  - [A preliminary study on the effect of prepubertal exposure of male rats to
      diethylstilbestrol on the apoptosis of spermatogenic cells after sexual
      maturation and its mechanism].
AB  - OBJECTIVE: To preliminarily study the effect of prepubertal exposure of male SD
      (Sprague-Dawley) rats to diethylstilbestrol (DES) on the apoptosis of
      spermatogenic cells after sexual maturation and its mechanism. METHODS: Thirty 21
      day-old male SD rats were randomly divided into 4 experimental groups, DES 0.01,
      0.1, 1.0 and 10.0 microg/(kg x d) and 1 control group. The experimental groups
      were injected (s.c.) with different doses of DES (dissolved in corn oil) during
      prepuberty [from postnatal day (PND) 22 to PND 35] and the control group with
      medium only. The apoptosis and related proteins Bcl-2 and Bax expressions of
      testicular spermatogenic cells were studied with TUNEL and immunohistochemistry
      after the rats sexual maturation (at PND 64). RESULTS: Compared with the control
      group, the apoptosis of testicular spermatogenic cells in the DES 0.01 microg/kg
      group had no difference, but significantly increased in the DES 0.1, 1.0 and 10.0
      microg/kg groups and the apoptosis increased with the increase of DES dose. In
      the control and DES 0.01 microg/kg groups, Bax protein expressed weakly but Bcl-2
      protein strongly in spermatogenic cells. With the increase of DES exposure, Bax
      protein expression in spermatogenic cells increased but Bcl-2 protein expression
      decreased. CONCLUSION: Prepubertal exposure of SD rats to inappropriate dose of
      DES can make the apoptosis of spermatogenic cells increase after sexual
      maturation. Bax and Bcl-2 proteins participate in the apoptotic course caused by
      prepubertal DES exposure.

PMID- 17009537
TI  - [Research progress in ectopic grafting of testicular tissues].
AB  - Since Nature published the first report in 2002 on using immunodeficient mice as
      recipients and allogeneous or heterogeneous testes as donor tissues to study the
      ectopic development of spermatogenic cells, the technique has been widely applied
      in various species (including human). In comparison with other in vitro
      maturation methods for male germ cells, testicular allografting or xenografting
      technique has such advantages as similar environment for the development of germ
      cells in physiological conditions, and better reproducibility. Up to now, sperm
      has been successfully produced by this technique from the testicular tisues of
      the immature mouse, hamster, cat, rabbit, pig, goat, bovine and rhesus monkey,
      and their offspring have even been generated by ICSI technique using the mouse
      and rabbit sperm derived from testis grafts. This article comprehensively reviews
      the development of the technique by discussing the influencing factors on the
      germ cell development in grafts including the variety and age of donors, the sex,
      integrity and immunity of recipients, the graft location and grafting time. And
      the applications of the technique and the existing problems are discussed as
      well.

PMID- 17009538
TI  - [Progress of researches on carnitines in the clinical therapy of andrology].
AB  - Carnitine, an important compound in the beta-oxidative process of mitochondrial
      fatty acid, plays a significant role in the cardiovascular, nervous, and
      reproductive system. Recently, carnitine has been used as a therapeutic in the
      treatment of male infertility, erectile dysfunction, Peyronie's disease, etc.
      Accordingly, the objective of this review is to summarize the progress in
      researches on carnitine as a clinical therapy in andrology.

PMID- 17009539
TI  - [Whole rehabilitation: a new goal of erectile dysfunction therapy].
AB  - Phosphodiesterase type 5 (PDE5) inhibitors effectively enhance the erectile
      function of the patients with erectile dysfunction (ED). The use of sildenafil
      citrate is expanding to a broader extent. Pulmonary artery hypertension has
      become a new indication of sildenafil. Sildenafil could improve the epithelial
      function in several vascular conditions in clinical trials. This article reviews
      the recent advances on basic and clinical studies of ED and sildenafil. On animal
      models, sildenafil could resume the cavernous epithelial function, up-regulate
      the protein expression of phosphorylated endothelial NO synthase (eNOS), reverse
      the decreased intracavernosal pressure (ICP) induced by pudendal artery blood
      flow restriction or hypoxia. In clinical studies, over 50% of ED patients
      receiving sildenafil got a fully rigid erection (grade 4 erection). And the same
      percentage of post-nerve-sparing radical prostatectomy patients receiving
      sildenafil obtained penile rehabilitation and spontaneously resumed erection
      sufficient for sexual intercourse. Sildenafil treatment has contributed to the
      normalization of self-esteem, confidence and sexual harmony in men with ED. All
      this suggests that a whole rehabilitation from erectile to psychosocial function
      may become a new goal of ED therapy.

PMID- 17009540
TI  - [Integrated treatment for azoospermia caused by radiotherapy after surgical
      treatment of spermatocytoma: a case report].
AB  - OBJECTIVE: To investigate a therapeutic method for male infertility caused by
      radiotherapy after surgical treatment of spermatocytoma. METHODS: A case of
      azoospermia caused by radiotherapy after surgical treatment of spermatocytoma was
      reported and the Chinese medicine Jiaweishuiluerxiandan was used as a major
      therapy for 3 years. RESULTS: The patient's health condition was improved
      dramatically two years after being treated by the Chinese medicine but no sperm
      was found in his semen. However, three years after the treatment, his
      spermatozoon density was recovered from zero to 2.0 x 10(6)/ml with normal
      morphology. His sperm was subsequently used for intracytoplasmic sperm injection,
      which made his spouse pregnant successfully, and an healthy male infant was born
      by caesarean birth. CONCLUSION: Chinese medicine is a successful try at treating
      male infertility caused by radiotherapy after surgical treatment of
      spermatocytoma. For those who have failed to get their sperm frozen before
      surgery, Chinese medicine is a choice for remediation.

PMID- 17009541
TI  - [Clinical trials of combined therapy of an oral Chinese medicine with massage for
      chronic nonbacterial prostatitis].
AB  - OBJECTIVE: To evaluate the clinical effect of an oral Chinese medicine combined
      with massage of the prostate in treating chronic nonbacterial prostatitis (CNP).
      METHODS: Seventy-two CNP patients were randomly divided into an experimental
      group (oral Chinese medicine with massage) and a control group (oral Chinese
      medicine only). The main parameters were compared before and two months after the
      treatment. RESULTS: Total efficacy rates of the experimental and control groups
      were 90.0% and 68.6%, respectively. Compared with the controls, patients in the
      experiment group had a lower score on NIH-CPSI, and the difference was
      significant statistically (P < 0.05). CONCLUSION: The combined therapy is more
      effective than oral Chinese medicine alone for the treatment of CNP.

PMID- 17009542
TI  - [Safety and tolerability of Vardenafil].
AB  - This paper reviewed the safety and tolerability of vardenafil in the treatment of
      erectile dysfunction (ED), including the general, cardiovascular and ocular
      safety. Results from clinical trials and practice experience demonstrated that
      vadenafil had good safety and tolerability, whether for general ED population or
      for difficult-to-treat ED patients, whether as short-term treatment or as long
      term therapy.

PMID- 17009543
TI  - Surgical practice in Hong Kong.
AB  - Surgery in Hong Kong has undergone a significant evolution over the past century.
      The quality of surgical care, medical education, surgical training and academic
      research has improved significantly through the joint efforts of the two
      universities, the government and the surgical colleges over these years. Surgical
      practice in Hong Kong continues to change also with the development of
      specialties/subspecialties, the changing pattern of disease and the development
      of new and effective treatments. Areas of clinical excellence in oesophageal
      cancer, hepatocellular carcinoma (HCC) and nasopharyngeal cancer (NPC) have
      gradually developed in these areas in Hong Kong. With the ongoing Westernisation
      and continued economic development in Hong Kong, some previously uncommon
      diseases will become more common. The surgical service in Hong Kong will need to
      continue to change to meet the new challenges in the future

PMID- 17009545
TI  - Surgical practice and medicine in the USA.

PMID- 17009544
TI  - Surgical practice in the UK.
AB  - Throughout the working lifetime of any surgeon, major changes take place often
      stimulated by matters outwith the practitioner's control. This has certainly been
      true over the last forty years. The holistic care of a patient is now well
      established, with surgeons being seen as doctors who can add technical skills to
      their therapeutic armamentarium rather than being speedy technicians. Many of the
      changes have been for the good of patient care and developments in other areas
      such as anaesthesia, intensive care and radiology have had a significant
      influence on surgical practice. Not all change has been for the better. Some of
      the Government pressures and concerns with financing of the Health Service have
      had an adverse affect by deviating attention away from the patient.

PMID- 17009546
TI  - The molecular mechanisms of skeletal muscle wasting: implications for therapy.
AB  - Skeletal muscle wasting is an important systemic manifestation of a wide range of
      diseases, including trauma, sepsis and cancer. The clinical consequences of
      muscle wasting undoubtedly include significant patient morbidity and worsened
      survival. Recently, there has been important progress in our understanding of the
      molecular mechanisms behind muscle wasting. In this review, the common systemic
      mediators, intracellular signalling pathways and effector mechanisms of skeletal
      muscle wasting are discussed with particular reference to different models of
      wasting and the development of novel therapeutic strategies.

PMID- 17009547
TI  - Modern challenges in colorectal cancer.
AB  - Colorectal cancer is a major problem worldwide and in the United Kingdom it is
      responsible for some 20,000 deaths per annum. Mortality from the disease is
      gradually decreasing in developed countries but, in the United Kingdom at least,
      its incidence is on the increase. In this article the major current challenges in
      colorectal cancer will be dealt with under the following headings: aetiology and
      prevention, early detection, diagnosis, surgery, adjuvant therapy and management
      of advanced disease.

PMID- 17009548
TI  - Management of spinal injury.
AB  - Spinal injury often affects young adults and results in debilitating neurological
      status, which in turn places a significant burden on society. This review article
      describes the current practice and controversies surrounding the management of
      spinal injury. General principles of pre-hospital management, resuscitation,
      medical treatment, surgical intervention and future advancement are reviewed.

PMID- 17009549
TI  - Recurrence after totally extraperitoneal laparoscopic repair: implications for
      operative technique and surgical training.
AB  - BACKGROUND: The totally extraperitoneal (TEP) approach is increasingly favoured
      for inguinal hernia repair. The learning curve is slow with high, early
      recurrence rates but the exact cause of recurrence is unknown. OBJECTIVE: To
      determine the reasons for recurrence, identify the critical operative steps and
      examine the influence of surgical experience and training on results. PATIENTS
      AND METHODS: All patients undergoing TEP between 1993 and 2004 were included.
      Patients requiring re-operation for recurrence were identified and examined in
      detail. RESULTS: Eight surgical teams performed 1682 TEP repairs. Fifty five
      hernias recurred (3.27%) with a median follow-up of seven years (range 1-11
      years). In six recurrences, the first repair was itself for recurrence and in 24,
      the initial repair was bilateral. The initial hernia was direct in 26 and
      indirect in 29 patients. These distributions were similar to a control sample. At
      re-operation, indirect recurrence was more common with 18 direct, and 37 indirect
      cases (P=0.020). At re-operation, when the original mesh could be identified (18
      repairs), it appeared to have moved superiorly in 13 cases. Typically, recurrence
      occurred in 10% of a surgeon's first 20 cases, 4% of the next 60 cases and
      falling to below 2% thereafter. CONCLUSION: TEP repairs have a tendency for
      indirect recurrence even after direct repair. Meshes tend to migrate superiorly.
      Results suggest that recurrence occurs most often because of failure to fully
      expose the deep inguinal ring and/or to adequately spread the mesh inferiorly and
      laterally. We recommend particular attention be paid to these technical aspects.
      Acceptable results are obtainable after an experience of 20 cases but further
      improvement in results occurs as experience reaches 80 operations. With a large
      number of consultants having little or no experience in TEP surgery, there is an
      urgent need for 'hands-on' training courses so that all patients have access to
      TEP, particularly those with bilateral or recurrent inguinal herniae.

PMID- 17009550
TI  - Vaccination therapy in malignant disease.
AB  - Improvement in survival among patients with early malignancy is well established
      in various cancers. However, long-term survival in those with advanced malignancy
      has changed little and this poses a major therapeutic challenge to clinicians.
      Anti-cancer immunotherapy is a novel approach, which is still experimental, but
      offers a new therapeutic strategy. In this review, we discuss the basic
      immunological interplay between the host immune system and the tumour, mechanisms
      of anti-tumour immune responses induced by immunotherapy and key in vivo pilot
      studies of active specific immunotherapy in various sold cancers, carried out
      during the last five years.

PMID- 17009551
TI  - A new look at an under-diagnosed poorly treated condition: restless legs
      syndrome.
AB  - Restless legs syndrome (RLS) is a common condition that is difficult to diagnose.
      However, once correctly diagnosed, its management is straightforward and evidence
      based. The purpose of this article is to familiarise clinicians with both the
      symptoms and diagnostic criteria for RLS and to elucidate secondary and often
      curable causes of this prevalent condition. There is also a concise review of its
      pathophysiology and current management strategies. The authors hope this article
      will raise awareness of this condition among clinicians and in doing so improve
      the quality of life for the patients affected by it.

PMID- 17009552
TI  - The evolution of plastic and maxillofacial surgery in the twentieth century: the
      Dunedin connection.
AB  - At the outbreak of the Second World War there were four full-time plastic
      surgeons in the United Kingdom: Gillies, Kilner, McIndoe and Mowlem, known
      universally as the 'big four.' Three were from New Zealand, two had been born in
      Dunedin (Harold Gillies and Archibald McIndoe) and two (McIndoe and Rainsford
      Mowlem) had studied medicine in Dunedin at the University of Otago. The story of
      Gillies and McIndoe is well known to many. Perhaps less well known are the
      contributions of Mowlem and Henry Pickerill, another surgeon with Dunedin
      connections, and how the futures of these men were shaped by a small 19th century
      Scottish settlement at the bottom of the South Island of New Zealand.

PMID- 17009553
TI  - OR leaders grapple with shortage; two-thirds are hiring new grads.

PMID- 17009554
TI  - Reforms to revamp Medicare payments.

PMID- 17009555
TI  - Fewer vacancies, lower turnover for ASCs.

PMID- 17009557
TI  - ASCs dismayed over new payment plan.

PMID- 17009556
TI  - Aiming for tighter glucose control.

PMID- 17009558
TI  - Inexpensive ideas to keep staff happy.

PMID- 17009559
TI  - Histomorphometric evaluation of six dental implant surfaces after early loading
      in augmented human sinuses.
AB  - This study investigated the bone-to-implant contact (BIC) and osteoconductive
      capacity (OC) of 6 different implant surfaces after early loading in humans. Two
      implants with different surfaces were placed side-by-side in the grafted (n= 5)
      and nongrafted (n = 1) sinuses of 3 volunteers. Single-tooth restorations were
      delivered 60 days later. After 6 months of full occlusal loading, implants were
      retrieved in block sections for histomorphometric analysis. One implant (acid
      etched) placed in grafted bone failed when loaded. There were no other
      complications. In grafted bone, the microtextured surface achieved the highest
      BIC value (94.08%), followed by the oxidized (77.32%), hydroxyapatite (HA)
      (74.51%), sandblasted and acid-etched (51.85%), and titanium plasma-sprayed (TPS)
      (41.48%) surfaces. In native bone, the acid-etched surface achieved a higher BIC
      value (69.03%) than the HA surface (59.03%). The highest OC value in grafted bone
      was exhibited by the microtextured surface (34.31%), followed by the HA (28.62%),
      sandblasted and acid-etched (25.08%), oxidized (17.55%), and TPS (-20.47%)
      surfaces. The HA surface exhibited a higher OC value (30.39%) in native bone
      compared with the acid-etched surface (24.0%). As a whole, highest BIC and OC
      values were exhibited by the microtextured surface, and lowest values were
      exhibited by the TPS surface. All other surfaces demonstrated excellent BIC
      (>50%) but varied in OC (range = 17.55%-28.62%). These findings are tempered by
      the limited scope and sample size of the study and should be considered
      preliminary. More research is needed to determine the impact of implant surface
      texture on BIC and OC.

PMID- 17009560
TI  - Preservation of the gingival architecture with the scalloped implant design: a
      clinical report.
AB  - Replacing the missing maxillary anterior teeth with dental implants and
      maintaining the soft tissue structure and alveolar profile is an esthetic
      challenge for the restorative dentist. This clinical report describes the
      immediate provisional placement and prosthetic rehabilitation of 2 missing
      maxillary central incisors with scalloped dental implants.

PMID- 17009561
TI  - Immediately loaded blade implant retrieved from a after a 20-year loading period:
      a histologic and histomorphometric case report.
AB  - Immediate loading of root-form dental implants has shown promising results and
      offers treatment cost and convenience advantages to patients. Although blade
      implants have been immediately loaded for over 2 decades, the ability of this
      implant design to achieve osseointegration has been debated. The aim of the
      present study was to histologically evaluate the peri-implant tissues of an
      immediately loaded blade implant retrieved for abutment fracture after a 20-year
      loading period. Histologic samples were prepared and examined by light
      microscope. Compact, cortical, mature bone with well-formed osteons was present
      at the interface of the implant. Bone-to-implant contact was 51% +/- 6%. The
      histologic data showed that osseointegration was obtained in an immediately
      loaded blade implant inserted into the mandible, and that mineralized tissues
      were maintained at the interface over a long period (20 years).

PMID- 17009562
TI  - Preferred collagen fiber orientation human peri-implant bone after a short- and
      long-term loading period: a case report.
AB  - Immediate loading of dental implants offers treatment cost advantages to patients
      and avoids the functional and psychological problems caused by the wearing of
      provisional dentures. There is evidence that the amount of transverse collagen
      fiber orientation in bone is influenced by mechanical stresses and strains. Two
      osseointegrated dental implants in humans were used in the present study. Two
      implants inserted in the maxilla were analyzed: 1 short-term implant (implant A)
      immediately loaded and retrieved after 4 months of loading and 1 long-term
      implant (implant B) immediately loaded and retrieved after 12 years. We
      hypothesized that the bone functional strain caused by immediate loading
      correlated well with the collagen fiber organization occurring after both short-
      and long-term functional healing. Circularly polarized light (CPL) was used to
      assess the area fraction extension related to the transverse collagen fiber
      orientation in the bone matrix. After evaluating a total of 68 digitized images
      taken at x50 magnification, birefringence measurements were performed all around
      the implant surfaces by using 2 central sections from each implant. The results
      showed that the bone-to-implant contact (BIC) percentage for implant A was 67.9%
      +/- 9.5% (mean +/- SD), whereas the BIC percentage for implant B was 74.6% +/-
      11.2% (mean +/- SD). The area fraction extension was 2.7% +/- 1.4 % (mean +/- SD)
      for implant A, whereas the area fraction extension was 4.7% +/- 1.2% (mean +/-
      SD) for implant B. The CPL measurements of the birefringence for transverse
      collagen fibers of implant A vs implant B indicated that the bone fraction area
      difference was not high. In the bone near both dental implants, no differences
      were found in the amount of transverse collagen fibers. Immediate loading seemed
      to determine and maintain the collagen fiber's orientation over a long period.

PMID- 17009563
TI  - Immediate implant placement: a case series.
AB  - A major drawback of implant therapy is the comparatively long healing period
      involved. Early and immediate loading of dental implants can significantly
      decrease the treatment time and thus result in an increase in patients' comfort.
      In this report, 3 cases of placement and immediate loading of the final implants
      are presented. In 2 of these cases, where preliminary augmentation was necessary,
      provisional implants were placed after the procedure and immediate provisional
      dentures were delivered. With the exception of 1 case, in which 1 implant failed,
      no adverse events were observed. All cases are in function now for 3 to 5 years
      after implant placement. The observations from this limited number of cases
      confirm that immediate loading of implants could be a viable treatment option.

PMID- 17009564
TI  - Maxillary single-tooth replacement utilizing a novel ceramic restorative system:
      results to 30 months.
AB  - This study reports on the first longitudinal results of an alumina (70%)-zirconia
      (30%) ceramic restorative system for implant-supported, single-tooth replacement
      in the anterior maxillary jaw. Eighteen patients (9 men, 9 women, mean age = 42.4
      years) were treated with 22 implants placed into 19 extraction sockets and 3
      residual ridges. Eight implants were immediately loaded with nonoccluding
      provisional prostheses. All implants were definitively loaded with fully
      occluding ceramic restorations after osseointegration and soft tissue maturation.
      Patients were monitored from 7 to 30 months (mean = 18.1 months) after loading.
      All implants osseointegrated and were successfully restored. One case of abutment
      screw loosening occurred because of patient parafunction (bruxing), and another
      patient reported chewing pain attributed to malocclusion. Both problems were
      successfully resolved without further incidence. Within the context of this
      study, single-tooth replacement in the anterior maxillary jaw was successfully
      achieved with alumina-zirconia ceramic single-tooth restorations with up to 30
      months of clinical function.

PMID- 17009565
TI  - Rationale for choices of occlusal schemes for complete dentures supported by
      implants.
AB  - This review of occlusal considerations for implant-supported complete dentures
      reflects the majority opinion of authors according to clinical observations and
      research-documented evidence. Occlusal concepts are presented for the implant
      supported complete dentures regarding analysis of loads applied to dental
      implants, location and number of implants, occlusal materials, and occlusal
      scheme.

PMID- 17009566
TI  - Population screening for colorectal cancer.
AB  - Each year in the UK, around 16,000 people die from colorectal cancer. At disease
      presentation, around 55% of people have advanced cancer that has spread to lymph
      nodes, metastasised to other organs or is so locally advanced that surgery is
      unlikely to be curative (Dukes' stage C or D). Overall 5-year survival for
      colorectal cancer in the UK is around 47-51% (compared to 64% in the USA), but
      only 7% at most in those presenting with metastatic disease. These facts underlie
      the current introduction of national bowel screening programmes in the UK. Here
      we assess the role of screening of the general population in reducing mortality
      from colorectal cancer. We do not consider the screening arrangements needed for
      high-risk populations, including those with inflammatory bowel disease or a
      strong family history of colorectal cancer.

PMID- 17009567
TI  - Dilemmas in managing Barrett's oesophagus.
AB  - In the UK, oesophageal adenocarcinoma accounts for over 7,000 deaths per year and
      its incidence is rising. One risk factor for this cancer is Barrett's oesophagus.
      In this condition, reflux of acid and duodenal fluid leads to replacement of the
      normal stratified squamous epithelium with a columnar epithelium. This new
      epithelium includes areas of intestinal metaplasia that may develop into
      dysplasia and ultimately carcinoma. Of people with Barrett's oesophagus, about 1%
      per year develop adenocarcinoma, around 30-125 times the rate in the general
      population. This carcinoma is asymptomatic until locally advanced, and has a poor
      prognosis unless detected early. So it has been suggested that people with reflux
      should be screened for Barrett's oesophagus, and those with the condition should
      be kept under surveillance to detect dysplasia or adenocarcinoma in the early
      stages. Here we discuss the problems in managing patients with Barrett's
      oesophagus.

PMID- 17009568
TI  - Knot-So-Fast: a learning plan to minimize patient restraint in critical care.
AB  - In 2001, new legislation in Ontario, the Patient Restraint Minimization Act,
      mandated that all hospitals develop a policy to minimize the use of restraints.
      Since restraining patients was a common practice in our intensive care unit
      (ICU), a practice change was necessary. To do this, a learning plan was created
      to share key information pertaining to the Act that would support humane and
      dignified care for our critically ill patients. Change was accomplished through a
      survey of nursing staff to establish learning needs, the development of a
      learning plan titled "Knot-So-Fast", and the creation of a tool titled the
      "Restraint Decision Wheel" to support staff in making restraint decisions quickly
      and appropriately. To measure the effect of our Knot-So-Fast learning plan, the
      staff was resurveyed one year later. Results showed there was a statistically
      significant decrease in restraint use in our ICU. The learning plan and tools
      developed have been found to be adaptable to other hospital units and are
      provided. This article includes the educational content and methods used in our
      ICU to effect a change in restraint practice. Tools, such as a nursing survey and
      a decision wheel, developed to enhance learning are also included.

PMID- 17009569
TI  - Reduction of musculoskeletal injuries in intensive care nurses using ceiling
      mounted patient lifts.
AB  - The musculoskeletal injury (MSI) rate in the Richmond Hospital Intensive Care
      Unit (ICU) increased significantly in 2000 and 2001 by 130%. As part of a quality
      initiative program, the problem was identified, assessed, and a plan was
      developed that involved the installation of ceiling-mounted patient lifts (CMPL)
      and the incorporation of a patient positioning sling. The evaluation process
      included a survey given to the ICU nursing staff prior to the implementation of
      the CMPL and repeated three, six, and 18 months after implementation. The survey
      included questions about discomfort, fatigue, and frustration levels before and
      after a 12-hour shift, as well as any medical interventions such as use of
      medications, physician visits, physiotherapy, and massage therapy for work
      related issues. The use of the lifts contributed to lower scores in fatigue, pain
      and frustration in addition to a reduction in medical visits. The results also
      demonstrated a significant reduction in work-related time loss claims while
      promoting a positive workplace environment.

PMID- 17009570
TI  - To err is human, to share is divine.
AB  - Front-line health care practitioners are often safety nets preventing errors from
      reaching patients. Nurses in critical care environments commonly deal with high
      risk patients, high-alert medications and extreme conditions, placing themselves
      and medication systems under greater pressures. Human error cannot be eradicated.
      However, the systems in which practitioners work and interact can be made safer
      and more fault-tolerant. When errors occur, nurses are in a unique position to
      provide valuable insights. Practitioner reporting and sharing of incident
      information internally and externally can enhance patient safety by helping to
      prevent recurrence of similar events.

PMID- 17009571
TI  - The Canadian ICU Collaborative to improve patient safety in the ICU: accelerating
      best practice to the bedside.

PMID- 17009572
TI  - Embracing technology? Using change management strategies to improve the use of
      continuous lateral rotation therapy.
AB  - The purpose of this quality improvement initiative was to improve the utilization
      of continuous lateral rotation therapy (CLRT) in a nine-bed community hospital
      ICU within the context of a nurse-driven protocol. Nursing focus groups, analyzed
      using a strength, weakness, opportunity, threat (SWOT) approach, resulted in the
      implementation of four interventions over seven weeks. Change management
      strategies guided all aspects of the project. Results showed a modest increase in
      the utilization of CLRT. This initiative demonstrates that change management
      strategies may assist with the incorporation of technology into nursing practice
      by increasing empowerment and creating an attachment to and responsibility for
      outcomes.

PMID- 17009573
TI  - Cardiac computed tomography: diagnostic utility and integration in clinical
      practice.
AB  - Cardiac applications of computed tomography (CT) is a rapidly growing diagnostic
      area because of the ability to visualize plaque burden (coronary artery
      calcification [CAC]) and luminal obstruction (computed tomographic angiography
      [CTA]) noninvasively. Coronary artery calcification has been validated in over
      1,000 studies over the last 20 years, primarily with electron beam tomography.
      Studies demonstrate several indications that could aid physicians in the
      management of symptomatic and asymptomatic patients. Determining that a
      symptomatic patient has no CAC is associated with both a lower risk of an
      abnormal nuclear study and angiographic obstruction. The ability to detect
      subclinical atherosclerosis (CAC) with minimal radiation and no contrast makes
      this an attractive method for risk stratification. New studies demonstrate a 10
      fold risk of cardiovascular events with increasing amounts of coronary
      calcification. The invasive nature, expense, and risk resulting from invasive
      angiography have been instrumental in encouraging the development of new
      diagnostic methods that allow the coronary arteries to be visualized
      noninvasively. Multislice CT, with its advanced spatial and temporal resolution,
      has opened up new possibilities in the imaging of the heart and major vessels of
      the chest, including the coronary arteries. The last decade has seen great
      strides in the field of cardiac imaging, particularly in the ability to visualize
      the coronary lumen with sufficient diagnostic accuracy. Possessing that
      qualification, CTA is now being used increasingly in clinical practice. As a
      result of having high spatial and improved temporal resolutions, this imaging
      modality not only allows branches of the coronary artery to be evaluated, but
      also allows simultaneous analysis of other cardiac structures, making it
      extremely useful for other cardiac applications. This paper reviews the
      diagnostic utility and limitations of cardiac CT and how it could be integrated
      into clinical practice.

PMID- 17009574
TI  - Clinical utility of contrast-enhanced echocardiography.
AB  - Over the past three decades, echocardiography has become a major diagnostic tool
      in the arsenal of clinical cardiology for real-time imaging of cardiac dynamics.
      More and more, cardiologists' decisions are based on images created from
      ultrasound wave reflections. From the time ultrasound imaging technology provided
      the first insight into a human heart, our diagnostic capabilities have increased
      exponentially as a result of our growing knowledge and developing technologies.
      One of the most intriguing developments that brought about a decade-long
      combination of expectations and disappointments was the introduction of
      echocardiographic contrast agents. Despite repeated waves of controversy
      regarding the readiness of this technology for clinical use, it has overcome
      multiple hurdles and currently provides useful clinical information that helps
      cardiologists to diagnose heart disease accurately. Since the initial reports on
      the use of ultrasound contrast media such as agitated saline or renografin, the
      major advances in the field of contrast echocardiography have included (1) the
      development of stable perfluorocarbon-filled microbubbles, frequently referred to
      as second-generation contrast agents; and (2) the development of contrast
      targeted nonlinear imaging modes, such as harmonic imaging, pulse inversion, and
      power modulation, which allow consistent real-time visualization of these agents.
      These contrast agents in conjunction with the new imaging technology constitute
      powerful tools that improve our ability to evaluate left ventricular function and
      myocardial perfusion, and allow differential diagnosis of thrombi and
      intravascular masses. In this manuscript, we briefly review some of the
      literature that has provided the scientific basis for the use of
      echocardiographic contrast agents in the context of these important variables.

PMID- 17009575
TI  - Nuclear cardiology: finally a one-stop shop for diagnosis, risk stratification,
      and management of coronary artery disease.

PMID- 17009576
TI  - Cardiovascular magnetic resonance imaging.

PMID- 17009577
TI  - Shining a light on hospital charges.
AB  - With growing insistence, consumers, legislators and payers want to know how much
      a hospital stay really costs--and health care leaders need to have answers.

PMID- 17009578
TI  - Complementary and alternative medicine--a consumer CAM-paign.
AB  - Complementary and alternative medicine (CAM) isn't just for the "New Age" set
      anymore-increasingly, patients are voting with their feet, choosing those
      institutions that offer CAM therapies.

PMID- 17009579
TI  - Back to basics 3. How to recruit your next CEO.

PMID- 17009580
TI  - 2006 NOVA Awards.
AB  - From projects helping the uninsured in Wisconsin to medical care on wheels in
      rural Kentucky, these award-winning hospitals share the common goal of improving
      health care in their own back yards.

PMID- 17009581
TI  - Self-evaluation: the foundation for board improvement.

PMID- 17009583
TI  - Docs cut loose.

PMID- 17009582
TI  - Effective trusteeship through teamwork.

PMID- 17009584
TI  - Three cheers for new IOM report.

PMID- 17009585
TI  - Physicians aggressively pursuing I.T.

PMID- 17009586
TI  - Integration: the gateway to online success.

PMID- 17009587
TI  - Clinical trials leave paper behind.

PMID- 17009588
TI  - Hospital learns to point, click and refer.

PMID- 17009589
TI  - I.T., laughter make good medicine.

PMID- 17009590
TI  - Keeping the ER on track.

PMID- 17009591
TI  - Reader's perspectives..."Outsourced I.T. services are better run than those that
      remain managed in-house. Do you agree or disagree"?

PMID- 17009592
TI  - Overexpression of heat shock factor 1 inhibits butyrate-induced differentiation
      in colon cancer cells.
AB  - Produced by dietary fiber, butyrate is a potential chemopreventive agent against
      colon cancer. It stimulates proliferation of normal colonic epithelial cells but
      induces growth inhibition, differentiation, apoptosis, or a combination of
      effects in colon carcinoma cells. In this study, we used cDNA membrane arrays and
      real-time reverse transcriptase-polymerase chain reaction to identify stress
      genes that were differentially regulated by sodium butyrate (NaB) in HT 29 human
      colon carcinoma cells. The results indicated that a group of heat shock protein
      (hsp) genes were upregulated by 3 mM NaB within the first 24 hours of exposure.
      Because the transcription of hsp genes is under the control of heat shock factors
      (HSFs), we measured the effects of overexpressed HSF-1 on the responses of HT 29
      cells to NaB. Overexpression of HSF-1 inhibited NaB-induced differentiation as
      measured by alkaline phosphatase activity and carcinoembryonic antigen
      expression. These results suggest that increased expression of HSFs and Hsps
      might render colon carcinoma cells resistant to the chemopreventive effects of
      butyrate.

PMID- 17009593
TI  - Reduced heat shock response in human mononuclear cells during aging and its
      association with polymorphisms in HSP70 genes.
AB  - Age-dependent changes in heat shock response (HSR) were studied in mononuclear
      cells (monocytes and lymphocytes) collected from young (mean age = 22.6 +/- 1.7
      years) and middle-aged (mean age = 56.3 +/- 4.7 years) subjects after 1 hour of
      heat shock at 42 degrees C. Genotype-specific HSR was measured by genotyping the
      subjects for 3 single nucleotide polymorphisms, HSPA1A(A-110C), HSPA1B(A1267G),
      and HSPA1L(T2437C), 1 each in the 3 HSP70 genes. A significant age-related
      decrease in the induction of Hsp70 occurred after heat shock in both monocytes
      and lymphocytes. The noninducible and inducible forms of Hsp70 decreased 1.3-fold
      (P < 0.001) and 1.4-fold (P < 0.001), respectively, in the monocytes with age. In
      the young subjects, a positive association was found between HSPA1L(T2437C)
      polymorphism and HSR. CC carriers had a significantly lower induction than TT
      carriers in both monocytes (P = 0.015) and lymphocytes (P = 0.044). This
      polymorphism, which is present in the coding region of HSPA1L gene, can affect
      the chaperoning function of Hsp70. These data consolidate our other observations
      that the CC genotype is unfavorable for human longevity and provide a functional
      explanation in terms of variations in HSR.

PMID- 17009595
TI  - Gene expression profiling of human endothelial cells exposed to 50-Hz magnetic
      fields fails to produce regulated candidate genes.
AB  - To address the question of a possible effect of magnetic fields (MF) at 50 Hz on
      living systems, gene expression analyses were performed on human primary vascular
      endothelial cells exposed to MF of various intensities compared to control cells.
      Exposure protocols included continuous exposure at a single intensity (10 and 700
      microT), intermittent exposure at a single intensity (700 microT), and continuous
      exposure to a variable-intensity field (10-30 microT). The transcriptional
      response of the cells was investigated using oligonucleotide microarrays
      containing up to 30 000 unique features. Although in individual experiments genes
      were identified where the expression appeared to be affected by exposure to MF,
      none of these genes were regulated in the same manner in subsequent repetition
      experiments. This is the first report of a transcriptome-wide analysis of the
      effects of MF exposure on human cells. The lack of a reproducible effect of MF on
      the expression of any genes in our investigation adds further weight to the
      evidence that 50-Hz MF are not capable of interacting with biological systems and
      thus do not represent an endothelial stress factor.

PMID- 17009594
TI  - Fusion proteins of Hsp70 with tumor-associated antigen acting as a potent tumor
      vaccine and the C-terminal peptide-binding domain of Hsp70 being essential in
      inducing antigen-independent anti-tumor response in vivo.
AB  - Hsp70s are a family of ATP-dependent chaperones of relative molecular mass around
      70 kDa. Immunization of mice with Hsp70 isolated from tumor tissues has been
      proved to elicit specific protective immunity against the original tumor
      challenge. In this work, we investigated whether Hsp70 can be used as vehicle to
      elicit immune response to its covalence-accompanying antigen. A recombinant
      protein expression vector was constructed that permitted the production of
      recombinant protein fusing tumor-associated antigen (eg, Mela) to the C terminus
      of Hsp70. We found that the Hsp70-Mela fusion protein can elicit strong cellular
      immune responses against murine tumor B16, which expresses protein Mela. The
      Hsp70 peptide-binding domain deletion mutant of the fusion protein was sufficient
      for inducing Mela-specific cytotoxic T lymphocyte but was not sufficient for
      engendering potent anti-tumor immunity against B16. We also found that host
      natural killer (NK) cells were stimulated in vivo by C-terminal domain of Hsp70.
      We thus presume that Hsp70 fusion proteins suppress tumor growth via at least 2
      distinct pathways: one is covalence-accompanying antigen dependent; another is
      antigen independent. The C-terminal domain of Hsp70 seemed to be the crucial part
      in eliciting antigen-independent responses, including NK cell stimulation,
      against tumor challenges. Furthermore, we found that immunization with multiple
      Hsp70 fusion proteins resulted in a better anti-tumor effect.

PMID- 17009597
TI  - Heat shock protein 70 enhanced deoxyribonucleic acid base excision repair in
      human leukemic cells after ionizing radiation.
AB  - Base excision repair (BER) of DNA damage in irradiated THP1 human leukemic cells
      was stimulated by pretreating the cells with exogenous recombinant Hsp70. The
      treatment of THP1 cells with recombinant Hsp70 in cell culture promoted repair by
      reducing the frequency of apurinic, apyrimidinic (AP) sites in DNA before and
      after 1.3 Gy of radiation. However, by 30 minutes after 2.6 Gy, accelerated
      repair of abasic sites supervened, which may contribute to the loss of the very
      low-dose cell hypersensitivity seen in clonogenic studies of other laboratories.
      After irradiation with 2.6 Gy, the crucial initial glycosylase step was markedly
      incomplete when cells had been transfected 24 hours before with a small
      interfering RNA (siRNA) designed to inhibit synthesis of Hsp70. In confirmation,
      lysates from irradiated siRNA-treated cells after 2.6 Gy were deficient in uracil
      glycosylase activity (UDG). Transfection with a scrambled RNA of the same size
      did not interfere with the glycosylase step, ie, the prompt conversion of damaged
      pyrimidine sites to abasic sites as well as the subsequent repair of those sites.
      BER measured by reduction of DNA AP sites before and after low-dose radiation was
      also deficient in THP1 cells that had been transfected with the siRNA designed to
      inhibit synthesis of Hsp70. These results implicate BER and the participation of
      Hsp70 in the repair of DNA in human leukemic cells with the doses of ionizing
      radiation used in clinical regimens.

PMID- 17009596
TI  - Association of hsp70 polymorphisms with risk of noise-induced hearing loss in
      Chinese automobile workers.
AB  - Severe noise exposure can induce heat shock proteins (Hsps), and exposure to
      moderate noise has been reported to confer protection against noise-induced
      damage to hearing. Whether there is any association of genetic variation in both
      constitutive and inducible hsp70 genes with noise-induced hearing loss (NIHL) is
      presently unknown. Using polymerase chain reaction-restriction fragment length
      polymorphism, we genotyped 3 polymorphisms (+190A/ B, +1267A/B, and +2437A/B) in
      the hsp70-1 (rs1043618), hsp70-2 (rs1061581), and hsp70-hom (rs2227956) genes,
      respectively, and investigated the associations of these polymorphisms with risk
      of developing NIHL in 194 automobile workers working in a similar noise
      environment as evaluated by audiological assessment. Multivariate logistic
      regression models were used to assess the associations with the risk genotypes,
      and Whap software was used to analyze their haplotypes. Our results showed that
      there was no statistically significant difference in the genotype and allele
      distributions of hsp70-1, hsp70-2, and hsp70-hom between the NIHL group and the
      normal group (P > 0.05) with and without adjustment for age, sex, smoking,
      history of explosive noise exposure, and cumulative noise exposure. However,
      haplotype analysis revealed that the Hap5 (ie, haplotype +190A/+1267B/+2437A) and
      Hap6 (ie, haplotype +190A/+1267B/+2437B) were significantly more frequent in the
      NIHL group than in the normal group (20/9, P = 0.022, and 7/0, P = 0.005,
      respectively). Compared with Hap1 (ie, +190A/+1267A/+2437A), Hap5 was associated
      with a nearly 3-fold increased risk of NIHL (adjusted odds ratio, 2.67; 95%
      confidence interval, 1.13-6.27). Seven of the NIHL patients had Hap6, but none of
      the controls had this haplotype. Our results suggest that some haplotypes of the
      hsp70 genes may be associated with a higher susceptibility to NIHL.

PMID- 17009599
TI  - Overexpression of heat shock protein 70 restores the structural stability and
      functional defects of temperature-sensitive mutant of large T antigen at
      nonpermissive temperature.
AB  - The effects of heat shock protein 70 (Hsp70), a molecular chaperone, on the
      degradation and functional alterations of a mutant large T antigen induced by a
      nonpermissive temperature were examined. In this study, mouse tracheal epithelial
      TM02-3 cells harboring temperature-sensitive simian virus 40 large T antigen and
      stable TM02-3 cells overexpressing human Hsp70 and/or Hsp40 were used. Although
      the temperature shift from 33 degrees C (permissive temperature) to 39 degrees C
      (nonpermissive temperature) induced increases in the endogenous chaperones
      including Hsp70 and Hsp40, degradation of the T antigen, activation of the p53
      p21(waf1) pathway, and an arrest of cell growth were observed in the mock cells.
      In contrast, these changes induced by the temperature shift were partially but
      significantly prevented in stable cells overexpressing human Hsp70 and/or Hsp40.
      A combination of Hsp70 and Hsp40 was the most effective, suggesting that Hsp40
      may cooperate with Hsp70. Moreover, immunocytochemical observation indicated that
      human Hsp70 was expressed in the cytoplasm at 33 degrees C, but it colocalized
      with T antigen in the nucleus at 39 degrees C. These results suggest that
      overexpressed Hsp70 translocates from the cytoplasm to nucleus, and significantly
      restores the structural stability and functional defects of mutant large T
      antigen in the cells.

PMID- 17009598
TI  - Heat shock proteins, end effectors of myocardium ischemic preconditioning?
AB  - The purpose of this study was to investigate (1) whether ischemia-reperfusion
      increased the content of heat shock protein 72 (Hsp72) transcripts and (2)
      whether myocardial content of Hsp72 is increased by ischemic preconditioning so
      that they can be considered as end effectors of preconditioning. Twelve male
      minipigs (8 protocol, 4 sham) were used, with the following ischemic
      preconditioning protocol: 3 ischemia and reperfusion 5-minute alternative cycles
      and last reperfusion cycle of 3 hours. Initial and final transmural biopsies
      (both in healthy and ischemic areas) were taken in all animals. Heat shock
      protein 72 messenger ribonucleic acid (mRNA) expression was measured by a
      semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method
      using complementary DNA normalized against the housekeeping gene cyclophilin. The
      identification of heat shock protein 72 was performed by immunoblot. In our
      "classic" preconditioning model, we found no changes in mRNA hsp72 levels or heat
      shock protein 72 content in the myocardium after 3 hours of reperfusion. Our
      experimental model is valid and the experimental techniques are appropriate, but
      the induction of heat shock proteins 72 as end effectors of cardioprotection in
      ischemic preconditioning does not occur in the first hours after ischemia, but
      probably at least 24 hours after it, in the so-called "second protection window."

PMID- 17009600
TI  - Induction of physiological thermotolerance in MDCK monolayers: contribution of
      heat shock protein 70.
AB  - Enhanced survival of both individual cells and whole organisms following a heat
      stress is termed thermotolerance. In organisms, the maintenance of tissue
      function rather than the survival of individual cells ultimately determines
      outcome following thermal challenge. We used MDCK kidney epithelial cells to
      compare alterations in chaperone activity (as a measure of cellular tolerance)
      and epithelial barrier function (as a measure of physiological tolerance) after
      thermal challenge. Quercetin, an inhibitor of heat shock factor-dependent
      transcriptional activity, both potentiated the effects of heat on naive
      monolayers and blocked conditioning of monolayers following moderate heat shock,
      suggesting a central role of heat shock protein (HSP) family members in the
      maintenance of epithelial integrity. We used MDCK cells that constitutively
      overexpressed HSP70 to demonstrate 2 functionally distinct components of the
      response of monolayers to thermal stress. The maintenance of epithelial barrier
      function during exposure to elevated temperatures is regulated by a complex
      network of processes that involve the actions of HSP70 but that are independent
      of alterations in chaperone activity as reflected by changes in the thermal
      inactivation/refolding of luciferase. In contrast, the restoration of barrier
      function following a heat stress is directly modulated by HSP70 in a manner that
      can be fully accounted for by changes in chaperone activity. This study
      demonstrates an important, albeit complex, protective role for heat shock
      proteins in the modulation of MDCK epithelial barrier function following a
      thermal stress.

PMID- 17009602
TI  - [Relationship of psychiatric comorbidity and treatment of panic disorder and
      agoraphobia].
AB  - INTRODUCTION: Besides numerous studies that examined various aspects of
      comorbidity in patients with panic disorder and agoraphobia and numerous studies
      that examined efficacy of different treatment modalities in these patients, there
      was no study that examined relationship of overall psychiatric comorbidity and
      treatment of patients with panic disorder and agoraphobia. OBJECTIVE: The
      objective of the study was to establish the effect of psychiatric comorbidity on
      treatment efficiency of patients with panic disorder and agoraphobia. METHOD: The
      sample of the study consisted of 119 patients with primary diagnosis of panic
      disorder and agoraphobia. The therapy of patients was based on the use of
      individual integrative model of treatment, which incorporated psycho
      pharmaceuticals (benzodiazepines and antidepressants) and cognitive-behavior
      therapy. Symptom severity was estimated by Panic and Agoraphobia Scale before and
      after the completion of treatment. Patients with comorbidity and patients without
      any comorbidity were compared by MANOVA and ANOVA with repeated measures.
      RESULTS: The results of the study showed that 91% of patients met diagnostic
      criteria of comorbid psychiatric disorder and these patients had more severe
      clinical picture than patients without any comorbid disorder before the
      treatment. The results also showed that, after the completion of treatment, there
      was a significant reduction of all analyzed symptoms, that the effects of
      treatment were significantly better in patients with psychiatric comorbidity and
      that comorbid psychiatric disorders had no negative effect on the main goals of
      the treatment. CONCLUSION: Based on these results, it may be concluded that: in
      patients with panic disorder and agoraphobia and comorbid psychiatric disorders,
      the pharmacotherapy must be based on simultaneous use of antidepressants and
      benzodiazepines, while standard cognitive-behavior therapy of patients with panic
      disorder and agoraphobia must be modified in case of the existing comorbid
      psychiatric disorders.

PMID- 17009603
TI  - [Executive functions in young patients with unipolar depression].
AB  - Neuropsychological deficits associated with unipolar depression are seen in a
      broad range of cognitive domains. Executive deficits may be prominent in
      depression. Investigation of executive functions in younger adult patients with
      unipolar depression has been the focus of our study. Twenty-two consecutively
      depressive inpatients (24-36 years) and 21 healthy control subjects, matched on
      age, gender, education and verbal IQ were included in the study.
      Neuropsychological tests for executive functions were applied to all subjects.
      Unipolar young depressives showed significantly reduced number of completed
      categories and more trials for completion of the first category on Wisconsin Card
      Sorting Test (WCST). No difference of tasks assessing the short-term memory,
      total errors on WCST, perseverative and non-perseverative errors, and of both
      phonemic and semantic conditions of verbal fluency was found between groups. The
      results suggested that unipolar depressives had specific cognitive style
      characterized by "negative cognitive set" (stronger negative reaction to negative
      feedback) and by failure to use negative feedback to improve their performance.

PMID- 17009601
TI  - Exogenous heat shock protein 70 mediates sepsis manifestations and decreases the
      mortality rate in rats.
AB  - Mammalian responses to bacterial lipopolysaccharide (LPS) from the outer membrane
      of Gram-negative bacteria can lead to an uncontrolled inflammatory reaction that
      can be deadly for the host. We checked whether heat shock protein 70 (Hsp70)
      protein is able to protect animals from the deleterious effects of bacterial LPS
      by monitoring the effect of exogenous Hsp70 injections before and after LPS
      administration. Our research with rats demonstrates for the first time that
      administration of exogeneous Hsp70 before and after LPS challenges can reduce
      mortality rates and modify several parameters of hemostasis and hemodynamics.
      Hsp70 isolated from bovine muscles showed significant protective effects against
      the impaired coagulation and fibrinolytic systems caused by LPS, and reduced the
      mortality caused by Escherichia coli and Salmonella typhimurium LPS injections
      significantly. Characteristically, Hsp70 preparations used in the experiments
      result in different effects when administered before and after an LPS challenge,
      and the effects of Hsp70 injections also differ significantly depending on the
      origin of the LPS (E coli vs S typhimurium). Based on our data, mammalian Hsp70
      appears to be an attractive target in therapeutic strategies designed to
      stimulate endogenous protective mechanisms against many deleterious consequences
      of septic shock by accelerating the functional recovery of susceptible organs in
      humans.

PMID- 17009604
TI  - [Most severe consequences of eye contusion injuries--surgical treatment].
AB  - INTRODUCTION: One third of all eye injuries are contusion injuries. The most
      common causes of contusion eye injuries are squash ball, fist fights, sports, and
      work with blunt objects. OBJECTIVE: The objective of our study was to analyze the
      surgical treatment methods and materials for managing the most severe
      consequences of eye contusion injuries. METHOD: A large number of complications
      of contusion eye injuries were treated at Department for Vitreoretinal Surgery of
      the Eye Clinic, Military Medical Academy, Belgrade. This paper analyzed two
      periods, from 1991-1999, and 2000-2004. During these periods, 461 patients with
      contusion eye injuries were surgically treated. Pars plana vitrectomy and
      phacoemulsification with PCL implantation were the most commonly performed
      operations. RESULTS: During the analyzed period, a total of 334 pars plana
      vitrectomies, 253 combined operations (PHACO+ VPP) and 214 operations with PCL
      implantation (PHACO+VPP+PCL) were performed. Scleral fixation was carried out in
      14 patients. After pars plana vitrectomy, some form of extended tamponade of
      vitreal space, in relation to degree of injury and complications, was performed
      in 194 cases. CONCLUSION: Eye traumatism is still one of the leading causes of
      vision loss (from the earliest ages) in our region. Preventive measures that
      could lead to decrease of eye injuries should be fully supported, not only
      through expert meetings and publications, but via media as well.

PMID- 17009605
TI  - [Splanchnic artery aneurysms].
AB  - INTRODUCTION: Splanchnic artery aneurysms are uncommon but important vascular
      entity because nearly 25% of all cases present as surgical emergency. OBJECTIVE:
      The purpose of our study was to present nine patients operated on at the
      Institute of cardiovascular diseases, as well as literature review of clinical
      presentation of the disease. METHOD: There were three splenic artery aneurysms,
      two celiac trunk aneurysms, and one aneurysm of the hepatic, superior mesenteric,
      inferior mesenteric and gastroduodenal artery. All patients were males, mean aged
      67.5 years (60-73). In four patients, splanchnic artery aneurysm was discovered
      accidentally during routine ultrasonographic and angiographic examinations of the
      abdominal aorta. At that time, arteriovenous fistula was diagnosed in a patient
      No 1; it was formed after rupture of the splenic artery aneurysm into the splenic
      vein. Three aneurysms were manifested by abdominal pain and palpable pulsating
      abdominal mass. Two patients were admitted as urgent cases in the state of
      hemorrhagic shock and signs of intraabdominal bleeding due to rupture of the
      splenic and hepatic arteries. In 7 cases, diagnosis was made preoperatively by
      means of ultrasonography and angiography; in two patients, accurate diagnosis was
      confirmed during surgery. RESULTS: Proximal and distal ligation of the artery was
      performed in a patient with rupture of the splenic aneurysm into the splenic vein
      that caused arteriovenous fistula. Gastroduodenal artery aneurysm was treated by
      trans-aneurysmatic ligation of its "entering" and "exiting" branches. Aneurysms
      of distal part of the superior mesenteric and splenic artery were resected
      without further reconstruction. Partial resection of the aneurysm and
      endoaneurysmorrhaphy was carried out in one case of celiac trunk aneurysm, and in
      another, after aneurysm resection, the restoration of blood flow through the
      hepatic and lienal artery was achieved by Dacron grafts. In a patient with the
      inferior mesenteric artery aneurysm, the resection of aneurysm was followed by
      reimplantation of medial part of the artery into bifurcated Dacron graft which
      replaced abdominal aorta. In 5 patients, some of additional surgical procedures
      were performed. There were 4 reconstructive procedures of abdominal aorta and one
      splenectomy. The patient with ruptured hepatic artery aneurysm died during
      surgery due to uncontrolled hemorrhage. In other patients, there was neither
      morbidity nor mortality in the early postoperative period (first 30 days after
      surgery). Mean follow up was 1 to 5 years (mean 3.4 years). One patient died
      after 5 years due to myocardial infarction. CONCLUSION: Although the introduction
      of precise diagnostic procedures (computerized tomography, magnetic resonance
      imaging, spiral scan) make diagnosis easier, the splanchnic artery aneurysms are
      still difficult to detect due to their uncommon clinical presentations.

PMID- 17009606
TI  - [The effect of propylthiouracil on function of phagocytic peripheral blood cells
      in persons with thyroid hyperfunction].
AB  - INTRODUCTION: It is known that hyperthyroidism as well as thyrosuppressive
      therapy can influence the cells of immunological system. OBJECTIVE: To examine
      the function of phagocyte cells in persons with hyperthyroidism and to examine if
      propylthiouracil (PTU) influences this function. METHOD: The study included 15
      patients with hyperthyroidism and 10 healthy persons. The parameters of
      phagocytic activity of mononuclear and polymorphonuclear leucocytes were tested
      by method of ingestion of particles of inactivated yeast labeled with neutral
      red. RESULTS: It was demonstrated that patients with hyperthyroidism, before the
      onset of therapy as well as 14 days after introduction of PTU, had decreased
      number of leucocytes (before PTU: 6.7 +/- 3.2 x 10(9)/l, after PTU: 6.1 +/- 2.0 x
      10(9)/l and control: 8.0 +/- 1.6 x 10(9)/l; p=0.039), PMN leucocytes (before PTU:
      3.9 +/- 2,4 x 10(9)/l, after PTU: 3.5 +/- 1.6 x 10(9)/l and control: 4.8 +/- 0.9
      x 10(9)/l; p=0.037) and number of phagocyte PMN cells (before PTU: 0.9 +/- 0.9 x
      10(9)/l, after PTU: 0.9 +/- 0.7 x 10(9)/l and control: 1.3 +/- 0.6 x 10(9)/l;
      p<0,05), but they had increased index of phagocytosis (before PTU: 2.0 +/- 0.2,
      after PTU: 1.9 +/- 0.2 and control: 1.7 +/- 0.2; p=0.029), while capacity of
      phagocytosis remained unchanged (before PTU: 1.9 +/- 1.7 x 10(9)/l, after PTU:
      1.6 +/- 1.9 x 10(9)/l and control: 2.4 +/- 1.4 x 10(9)/l; p>0.05). The number of
      mononuclear leucocytes and parameters of phagocytic activity of mononuclear
      phagocytes in persons with hyperthyroidism did not change significantly in
      comparison with the control group. CONCLUSION: Patients with hyperthyroidism had
      decreased number of leucocytes, PMN leucocytes and number of phagocyte PMN cells,
      and increased index of phagocytosis, while capacity of phagocytosis remained
      unchanged. The number and parameters of phagocytic activity of mononuclear
      leucocytes did not change. PTU therapy had no effect on the examined parameters.

PMID- 17009607
TI  - [Influence of hormone replacement therapy in postmenopausal women with type 2
      diabetes and hyperlipidemia on lipid and glucose metabolism].
AB  - INTRODUCTION: Hormone replacement therapy (HRT) is less frequently prescribed to
      postmenopausal women with diabetes type 2 who have poor lipid status despite well
      known favorable effect of HRT on lipid levels. OBJECTIVE: The aim of this study
      was to assess the effect of oral HRT in postmenopausal women with type 2 diabetes
      and hyperlipidemia. METHOD: Continuously combined HRT, estradiol 2mg +
      norethisterone acetate 1mg was given to 30 women with diabetes type 2 and
      hyperlipidemia and two control groups of postmenopausal women (30 with
      hyperlipidemia only and 30 healthy women) over a 6-month period. Total
      cholesterol (t-HOL), triglycerides, LDL-cholesterol, HDL-cholesterol,
      glycosylated hemoglobin A1c (HbA1c) were evaluated in 3-month intervals. Fasting
      and postprandial glucose levels were evaluated monthly. RESULTS: HRT
      significantly decreased levels of t-HOL (X2(Friedman) = 11.712; p<0.01) and LDL-c
      (X2(Friedman) = 10.403; p<0.01) in postmenopausal women with type 2 diabetes.
      However, the effect was more pronounced in two control groups. Triglycerides
      (X2(Friedman) = 5.400; p > or = 0.05) and HDL-c (X2(Friedman) = 1.113; p>0.05)
      did not change in postmenopausal women with type 2 diabetes. Six month of oral
      HRT significantly decreased HbAlc (F=44.693; p<0.01). Fasting and postprandial
      glycemia was decreased but not significantly (X2Friedman=6.527; p>0.05).
      CONCLUSION: Six-month application of HRT is effective in lowering the lipid
      levels and HbA1c in postmenopausal women with type 2 diabetes. However, target
      lipid levels were not achieved.

PMID- 17009608
TI  - [Five-year experience with ileal neobladder according to original and modified
      Hautmann method].
AB  - INTRODUCTION: Radical cystectomy is the method of treatment of muscle invasive
      tumor of the urinary bladder, T2-T4a, N0-Nx, M0, which is also performed in
      patients at high risk of superficial tumors G3, CIS (carcinoma in situ), which
      are resistant to BCG and diffuse papillary tumors which can not be controlled by
      conservative treatment. After radical cystectomy, an adequate derivation of the
      urine is needed, and in the best interest for patient's comfort, is to make a new
      bladder from the parts of gastrointestinal tract and suture it to the rest of the
      urethra. In 1988, German surgeon Richard Hautmann published his method of
      creating a new bladder, for what he used 60cm of ileum. This method is in use at
      Department of Urology, Military Medical Academy, Belgrade, but, we introduced our
      modification of original operation because of early and late postoperative
      complications. OBJECTIVE: The analysis of early and late complications after
      derivative surgery of orthotopic ileal bladder according to Hautmann. The
      patients operated according to original and modified method were analyzed.
      METHOD: From 2000-2004, 117 radical cystectomies were performed due to malignant
      urinary bladder tumors as well as the same number of derivative surgeries at the
      Clinic for Urology, Military Medical Academy, Belgrade. During this five-year
      period, the orthotopic ileal neobladder surgery according to Hautmann was
      performed in 41 patients after radical cystectomy. Twenty three patients were
      operated on using the original method and 18 patients by our modification.
      RESULTS: Metabolic disorders and problems of high capacity of neobladder were
      manifested in all patients operated on by original method, while the stenosis of
      the ureteroileal anastomosis was present in most of these patients. Metabolic
      disorders were less frequent and of lower degree in patients operated by our
      modification and there was no stenosis of the ureteroileal anastomosis. The
      problems with urination were not reported. CONCLUSION: In our opinion and on the
      basis of our experience, Hautmann method is the method with fewer complications.
      However, our modifications are also acceptable because the number of
      complications is smaller and the value of operation is being kept.

PMID- 17009609
TI  - [Ovarian cysts and tumors as the cause of isosexual pseudoprecocious puberty].
AB  - INTRODUCTION: Precocious puberty in girls is generally defined as appearance of
      secondary sexual characteristics before eight years of age. Menarche before the
      ninth birthday may serve as an additional criterion. Precocious puberty is
      divided in central precocious puberty and pseudoprecocious puberty. Central
      precocious puberty (GnRH dependent) occurs because of premature activation of
      hypothalamic-pituitary-gonadal axis and activity of gonadotrophins.
      Pseudoprecocious puberty (GnRH independent) is caused by activity of sexual
      steroids that are not the result of gonadotrophin activity. OBJECTIVE: Objective
      of our study was to examine the etiology, clinical and laboratory manifestations
      of isosexual pseudoprecocious puberty in girls. METHOD: In the period between
      1995 and 2004, clinical and laboratory sings of 34 girls with precocious puberty
      were studied at the Endocrine Department of the Institute of Mother and Child
      Health Care of Serbia. Initial evaluations included height measurement, staging
      of puberty, bone age assessment and pelvic ultrasound. Important diagnostic
      sonographic parameters of precocious puberty were the volumes of ovaries and
      uterus as well as ovarian structure. The initial hormonal evaluation included
      measuring of plasma oestradiol, luteinizing hormone (LH) and follicle stimulating
      hormone (FSH). The luteinizing hormone releasing hormone (LHRH) stimulation test
      was used to evaluate LH and FSH responsiveness (60 microg/m2 LHRH-Relefact LHRH,
      Ferring). Blood samples were collected at 0, 20 and 60 minutes. Basal and GnRH
      stimulated LH and FSH were determined by immunoradiometric assay. Estradiol
      concentration was measured using the fluoroimmunometric assay. RESULTS: Thirty
      four girls aged 6 months to 9 years (mean age 4.5 years) with precocious puberty
      were studied during the period of 9 years. Eleven girls presented with breast
      development, six with vaginal bleeding and seventeen with signs of puberty. On
      the basis of clinical signs, bone age, estradiol levels and LHRH test, premature
      thelarche was diagnosed in eleven patients (32.4%), premature menarche in six
      (17.6%) and central precocious puberty in ten girls (29.4%). Seven girls (20.6%)
      presented with pseudoprecocious puberty. Pelvic ultrasound examination revealed
      unilateral ovarian cysts in six patients and granulosa cell tumor in one.
      Elevated estrogen serum levels and failure of gonadotropin responses after
      gonadotropin releasing hormone were the classical findings in patients with
      isosexual pseudoprecocious puberty during the acute period of disease. In four
      patients, the cyst decreased spontaneously after several months, while in two
      patients, the cyst was removed by laparotomy. Surgical treatment was performed in
      a patient with granulosa cell tumor. CONCLUSION: Our work demonstrates that
      autonomous functional ovarian follicle cyst is the most often cause of isosexual
      pseudoprecocious puberty. Short period of observation is suggested because the
      cyst can resolve spontaneously. On the other hand, juvenile granulosa cell tumor,
      as highly malignant tumor, should be removed as soon as diagnosis is established.

PMID- 17009610
TI  - [Ewing sarcoma--analysis of epidemiological parameters and their relation to
      clinical characteristics].
AB  - The purpose of this investigation was to evaluate epidemiologic features of Ewing
      sarcoma in children treated in the Institute for Orthopedic Surgery "Banjica: as
      well as to establish relation of these features to clinical findings. Study
      involved 78 patients treated over 20-year period (1980-2000). Analysis included
      standard epidemiologic data (age, sex, tumor localization) and diagnostic
      clinical features on presentation (major symptoms, time elapsed between
      presentation and diagnosis, presence of metastases). Most of the patients were in
      the age group of 15-18 years (50.0%), predominantly males. In general, the
      results of our study were consistent with data reported in literature.
      Nevertheless, this investigation revealed slightly higher incidence in patients
      younger than four years of age (5.1%); localization on the upper extremity was
      found to be more frequent (upper to lower extremity ratio was nearly 3:1 in our
      study), and the time lost between presentation and diagnosis was markedly reduced
      (average time elapsed between presentation and diagnosis was 2.5 months). The
      results of our study may improve efficiency and success of treatment, thus
      providing the basis of better prognosis in management of such a serious illness.

PMID- 17009611
TI  - [Insulin sensitivity in patients with adrenal incidentaloma].
AB  - INTRODUCTION: Frequent use of modern imaging methods (such as ultrasound, CT and
      MRI) results in high incidence of accidentally discovered adrenal mass. Adrenal
      incidentalomas are accidentally discovered adrenal tumors by imaging methods
      without any prior suspicion of adrenal disease. Some studies have shown decreased
      insulin sensitivity in patients with adrenal incidentaloma. OBJECTIVE: The
      objective of our study was to assess the insulin sensitivity in patients with
      adrenal incidentalom a. METHOD: A total of 22 patients with accidentally
      discovered adrenal mass confirmed by CT/MRI were evaluated in our study. Average
      age was 53.31 +/- 26.5 years and average BMI 25.84 +/- 3.65 kg/m2. Control group
      consisted of 33 healthy subjects. Insulin sensitivity was assessed by short ITT
      (insulin tolerance test). Blood samples were taken before, 3, 6, 9, 12, 15, 20
      and 30 minutes after i.v. bolus of regular insulin (0.05 IU/kg BW). Glycemia was
      determined by glucose oxidase method. Statistical analysis was done by ANCOVA,
      using BMI as covariate. RESULTS: Our results showed significantly lower insulin
      sensitivity in patients with adrenal incidentalomas comparing to the control
      group (4.95 +/- 0.58 vs. 6.62 +/- 0.47, p=0.015). CONCLUSION: Our patients with
      adrenal incidentalomas manifested lower insulin sensitivity what suggested
      further follow up and assessment of insulin sensitivity during endocrine
      evaluation of these patients.

PMID- 17009612
TI  - [Review of the extratransference intervention practice in the psychoanalytic
      psychotherapy].
AB  - The transference analysis takes the central position of the work in
      psychoanalytic psychotherapy. The work in extratransference sphere and experience
      in practical work with extratransference interventions are not often reported in
      expert literature. Extratransference sphere includes less transferring relation
      to the psychotherapist, transference on the other objects, or may refer to the
      external reality rather than the psychic reality or fantasy. In our illustration,
      we gave emphasis to extratransference interventions. Application of genetic
      interpretation and reconstruction were demonstrated as well, which can restore
      and establish connections between past and present, in order to understand
      influences of the past and current reality, and helping us to resolve infantile
      conflicts. Interpretation of extratransference situations is an important part of
      the analytical work and it is the essential category of interpretation. Analytic
      understanding should include transference and extratransference spheres, fantasy
      and reality, past and present. Working with neurotic patterns and character
      resistance needs an optimal choice of intervention in a given moment of analytic
      process. Extratransference interventions are the essential category of
      intervention, irreplaceable for their effectiveness in analytic process.

PMID- 17009613
TI  - [Hemangioma of the spleen].
AB  - Although the most frequent benign tumors of the spleen, hemangiomas are very
      rare, much rarer than hemangiomas of the liver. They manifest as localized
      (either single or multiple) or diffuse lesions, vary from solid to cystic,
      histologically from capillary to cavernous. Usually, they are small in size (1-3
      cm), rarely larger and very rarely of large size. A 67-year old woman admitted to
      Institute of Hematology, CCS, for investigation of the left upper abdominal pain,
      loss of appetite, loss in weight and malaise. As the investigation showed a
      number of hypoechogenic lesions within the enlarged, diffusely non-homogenic
      spleen, splenectomy was indicated. The spleen weighing 2600 grams was removed, in
      which the number of lesions histologically corresponded to hemangioma of the
      spleen. Postoperative recovery was uneventful. The patient has remained symptom
      free more than two years after surgery.

PMID- 17009614
TI  - [Infected giant liver cyst].
AB  - Congenital liver cysts are not as rare as it was thought in the past. Thanks to
      new imaging diagnostic techniques, these cysts have been discovered with
      increasing frequency. Uncomplicated congenital liver cysts are usually
      asymptomatic or followed by mild symptoms. Various complications of these cysts
      were reported. Infection of the congenital liver cyst is, however, very rare
      complication. A 65-year old man with huge infected congenital central liver cyst
      containing 3400 ml of pus from which Escherichia coli was cultivated was
      presented. The patient had a number of other histologically confirmed congenital
      cysts of the liver and the cyst of the left kidney. The patient was cured by pus
      evacuation, partial excision of the cyst wall and drainage of the cavity and
      subphrenic space. The uninfected cysts were operated using deroofing technique. A
      year after surgery the patient remained symptom free.

PMID- 17009615
TI  - [Postoperative cognitive deficits].
AB  - Cognitive dysfunctions are relatively common in postoperative and critically ill
      patients. This complication not only compromises recovery after surgery, but, if
      persistent, it minimizes and compromises surgery itself. Risk factors of
      postoperative cognitive disorders can be divided into age and comorbidity
      dependent, and those related to anesthesia and surgery. Cardiovascular,
      orthopedic and urologic surgery carries high risk of postoperative cognitive
      dysfunction. It can also occur in other types of surgical treatment, especially
      in elderly. Among risk factors of cognitive disorders, associated with
      comorbidity, underlying psychiatric and neurological disorders, substance abuse
      and conditions with elevation of intracranial pressure are in the first place in
      postoperative patients. Preoperative and perioperative predisposing conditions
      for cognitive dysfunction and their incidence were described in our paper. These
      are: geriatric patients, patients with substance abuse, preexisting psychiatric
      or cognitive disorders, neurologic disease with high intracranial pressure,
      cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent
      porphyria, operation type, brain hypoxia, changes in blood glucose level,
      electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative
      awareness. For each of these factors, evaluation, prevention and treatment
      strategies were suggested, with special regard on anesthetic technique.

PMID- 17009616
TI  - [Functional voiding disorders: rehabilitation of children with urge syndrome].
AB  - Urge syndrome is a condition associated with functional voiding disorders.
      Urological symptoms (urgency, frequency and incontinence) are manifestations of
      uninhibited detrusor contractions. The goal of rehabilitation programs is to
      develop voluntary bladder control, to improve urologic symptoms and to increase
      bladder capacity. Bladder training, strategies to suppress urgency, electrical
      stimulations such are anogenital, transcutaneous and percutaneous electrical
      nerve stimulations have been used in the treatment.

PMID- 17009617
TI  - [The significance of the ovarian arteriolar vasodilatation in pathogenesis of the
      ovarian hyperstimulation syndrome].
AB  - Ovarian hyperstimulation syndrome is a complication of the ovulation stimulation,
      most commonly by gonadotrophins. It frequently occurs in patients included in in
      vitro fertilization program. The exact mechanism of development of this syndrome
      has not been elucidated yet. The basic pathogenic mechanism of development of
      this syndrome is vasodilation of the ovarian blood vessels. Dilated ovarian blood
      vessels become permeable. Permeability of dilated ovarian blood vessels is more
      increased by released ovarian mediators. Due to increased permeability of the
      blood vessels, there is leakage of the intravascular fluid into the extravascular
      areas resulting in hypovolemia, edema and ascites. Hypovolemia leads to renal
      perfusion decrease. Increased salt and water reabsorption occurs in the renal
      tubules so oliguria develops. Decreased arterial blood volume results in
      stimulation of the renin-angiotensin-aldosterone system, the sympathetic nervous
      system as well as the antidiuretic hormone. The activation of the sympathetic
      nervous system via beta adrenergic receptors stimulates renin release and
      aldosterone secretion. Renin stimulates release of angiotensin I which transforms
      into angiotensin II. Angiotensin II increases the pressure and stimulates
      aldosterone secretion. In patients with this syndrome, there is an elevated
      plasma endothelin and natriuretic peptide level. Endothelin is an important
      vasoconstrictor. It increases secretion of renin, aldosterone, catecholamines,
      antidiuretic hormone, and atrial natriuretic peptide, and enhances the
      vasoconstrictive effect of norepinephrine and angiotensin II. The platelet number
      increase together with the elevated factor of blood coagulation and
      hyperviscosity in a severe form of this syndrome may result in development of
      intravascular thrombosis. The treatment consists of maintenance of circulatory
      function, i.e. the increase of effective arterial blood volume by applying the
      plasma volume expanders.

PMID- 17009618
TI  - [Ewing sarcoma--current opinion].
AB  - Ewing tumor family consists of Ewing tumor of bone, extraosseous Ewing tumor,
      primitive neurectodermal tumor and Askin tumor. All of them share genetic
      abnormality, reciprocal translocation (11; 22) (q24; q12), and originate from the
      same primordial stem cell. Ewing tumor is the most common form, found in 60% of
      cases. It is the second primary malignant bone tumor. Localized lesion is found
      in nearly 80% and metastatic disease in 20% of cases. Patients present mostly due
      to pain and palpable tumefaction, and pathological fracture as the initial
      problem develops in long bones. Ewing tumor can develop in virtually any bone of
      the body and in extraosseous localizations as well, while localization in the
      extremities occurs in 50% of patients. Head or neck localizations are extremely
      rare. Paraspinal, retroperitoneal or deep pelvic tumor localization is manifested
      by back pain. Systemic symptoms are also present, commonly fever or weight loss,
      which often indicates the presence of metastatic disease with predominant
      invasion of lung, bone and bone marrow. Multimodal chemotherapy with local
      radiation and/or surgical resection is the best way of modern treatment. Distal
      parts of extremities and axial skeleton are good prognostic features, while
      proximal parts, pelvic girdle, metastatic disease and low index of
      postchemotherapeutic necrosis are associated with poor outcome.

PMID- 17009619
TI  - The establishment of primary health care and transition period in Turkey.

PMID- 17009620
TI  - The sentinel node biopsy in patients with breast cancer; many controversies
      remain.
AB  - The sentinel node procedure has increasingly been used as a diagnostic tool for
      staging breast cancer. Although many institutes have embraced this procedure,
      many issues concerning the indications and the technique itself remain unsolved.
      In this review, several aspects regarding these controversies are discussed from
      the perspective of The Netherlands Cancer Institute. These include the
      definitions used to identify the sentinel node, the indications and
      contraindications for this procedure and the injection site of the tracer and
      blue dye. What are the clinical implications of a micro-metastasis in the
      sentinel node? What is the best treatment for patients with an involved axillary
      node? Should non-axillary sentinel nodes be pursued, and if so, what are the
      implications for further management of these patients? Finally, the current TNM
      system is discussed in perspective of the evolving sentinel node procedure.
      Although many questions remain to be solved, the regional recurrence rates are
      low when axillary clearance is omitted because of a tumor-free sentinel node.

PMID- 17009621
TI  - International Society for the Study of Vulvovaginal Disease--founders lecture.

PMID- 17009622
TI  - Vaccination against human genital papillomaviruses. More than a hypothesis.
AB  - Human genital papillomaviruses are the necessary cause of cervical cancer. A
      prophylactic vaccine designed to prevent genital HPV disease by inducing virus
      neutralizing antibodies has been proposed. Studies on animal models have produced
      relevant data on the efficacy of HPV vaccine. The results of HPV clinical studies
      suggest that it will be possible to develop an effective vaccine. Nevertheless
      the number of subjects analyzed in the full text published clinical studies is
      still poor. Although a recently presented phase III study appears satisfied, it
      is probably necessary for a larger phase III study. Besides the choice of the
      geographical area for a very large clinical trial, there are different aspects to
      consider, such as the identification of the target population, identification of
      the endpoints, composition of the vaccine and marketing of the vaccine.
      Furthermore there are two open questions: the duration of protection and the
      behavioral modifications. All these issues are discussed in this review.

PMID- 17009624
TI  - Serum CA125 level modifications in women undergoing repeated IVF cycles.
AB  - In the present paper, serum CA125 modifications in patients undergoing their
      first IVF cycle were compared with those of patients in their second attempt. A
      significant increase of this marker was detected in each group of patients at day
      14 after embryo transfer. However, the level of CA125 monitored in the patients
      in their second attempt was significantly higher than that determined in patients
      undergoing their first ovarian stimulation. This condition does not influence
      either ovarian response or oocyte and embryo quality. Moreover similar IVF
      outcome was obtained. Therefore we propose that patients undergoing repeated
      assisted reproductive technology (ART) cycles may suffer from ovarian surface
      epithelial damage and/or altered cellular growth rate.

PMID- 17009623
TI  - Jun and Fos family protein expression in human breast cancer: correlation of
      protein expression and clinicopathological parameters.
AB  - OBJECTIVES: The activator protein-1 (AP-1) is a dimeric transcription factor
      formed by members of the Jun and Fos protein family. AP-1 plays a role in a
      variety of physiological functions including cell proliferation and
      differentiation, although both c-Jun and c-Fos have also been implicated in
      oncogenic transformation and tumor progression. To further elucidate the role of
      AP-1 in breast cancer, we have investigated the expression of the AP-1 proteins c
      Jun, JunB, JunD, phosphorylated c-Jun, c-Fos, Fral, Fra2 and the tumor supressor
      protein p53. METHODS: Protein expression was evaluated on a breast cancer tissue
      microarray with 58 lymph node positive or negative breast cancer specimens, 29
      corresponding lymph node metastases, and 11 tissue samples from surrounding tumor
      free tissue, each cored as triplicate. Jun and Fos protein family expression was
      evaluated by immunohistochemistry and was correlated with clinicopathological
      parameters. RESULTS: High expression levels were observed for c-Jun, JunD, c-Fos
      and Fra2, whereas JunB and Fral exhibited lower staining. c-Jun protein
      expression was correlated to Fral staining (p = 0.007, Kendall's Tau) and Fral
      was further associated with c-Fos (p < 0.001), JunD (p = 0.001) and Fra2 (p =
      0.011) expression. JunD expression correlated with c-Fos (p < 0.001), JunB (p =
      0.035) and c-Jun (p = 0.05). Activated c-Jun correlated with c-Fos expression (p
      = 0.041). JunB was negatively correlated to tumor stage, (p = 0.093, corr coeff.
      = -0.293, Spearman's correlation) but was significantly increased in nodal
      negative tumors (p = 0.004, Mann Whitney test). In addition, increased Fral
      expression showed a trend towards an increased overall survival (p = 0.077, RR =
      0.534, Cox regression). CONCLUSION: Our results suggest an important role for
      JunB and Fral in the biological behavior of malignant breast tumors.

PMID- 17009625
TI  - Preliminary results of mitomycin C local application as post-treatment prevention
      of vaginal radiation-induced morbidity in women with cervical cancer.
AB  - PURPOSE: To determine the usefulness of local mitomycin C application in the
      prophylaxis of vaginal narrowing after irradiation. MATERIAL AND METHODS: 31
      patients with advanced cervical cancer qualified for the study. They underwent
      brachytherapy with iridium-192 isotope and external beam therapy with linear
      accelerators. In a blind probe method 16 patients were chosen to have an aqueous
      solution of mitomycin C applied to the vagina. RESULTS: Radiotherapy caused a
      shortening of vaginal length in both groups (study and control). In the
      "mitomycin C group" complete vaginal occlusion was visibly less frequent as were
      solid fibrotic vault changes. CONCLUSIONS: This mode of morbidity prevention can
      potentially diminish the occurrence of local vaginal fibrosis and thus may
      improve patients' quality of life. Further investigations are needed to confirm
      these results.

PMID- 17009626
TI  - Sentinel node detection with the blue dye technique in early cervical cancer.
AB  - OBJECTIVE: The aim of this study was to investigate the feasibility of sentinel
      node detection with the blue dye technique in early cervical cancer. METHODS: In
      a retrospective study conducted between January 2000 and February 2005, 47 women
      with early cervical cancer (6 patients FIGO Stage I A, 38 patients FIGO Stage I
      B, 2 patients FIGO Stage II A, 1 patient FIGO Stage II B) who underwent class II
      III radical hysterectomy with pelvic lymphadenectomy were identified. Prior to
      surgery 1 ml of blue dye (lymphazurin 1%) was injected into the four quadrants of
      the cervix. RESULTS: The detection rate for sentinel nodes was 83% (39/47
      patients). The median number of sentinel lymph nodes per patient was two. Nine
      patients had positive sentinel nodes. In one patient the sentinel lymph node
      procedure revealed to be false-negative. Positive predictive value and
      specificity were both 100%. The sensitivity and negative predictive value were
      90% and 97%, respectively. CONCLUSIONS: Sentinel node detection has become a main
      field of interest in gynecological oncology. Our detection rate and sensitivity
      rate using the blue dye technique in cervical cancer are comparable to those in
      previously published data. However, recent data on a combined radioactively
      labeled albumin and blue dye technique show even more promising results. The
      clinical validity of the combined techniques must be evaluated prospectively in
      larger studies.

PMID- 17009627
TI  - VEGF induces phosphorylation of STAT3 through binding VEGFR2 in ovarian carcinoma
      cells in vitro.
AB  - VEGF plays a key role in ovarian carcinoma. Recent studies have shown that
      expressions of VEGF and its receptors were correlated with signal tranducer
      phosphorylation and activators of transcription 3(p-STAT3) in ovarian carcinoma.
      The aim of this study was to investigate the effects of STAT3 phosphorylation on
      VEGF signaling pathways in ovarian carcinoma cells. We selected an ovarian
      carcinoma cell line Caov-3 as a target cell that co-expressed VEGFR2 and p-STAT3.
      We detected expressions of p-STAT3 in Caov-3 induced by VEGF with different
      concentrations and for different effect times by immunocytochemistry and Western
      Blot. A concentration of 50 ng/ml VEGF was enough to increase phosphorylation of
      STAT3, and at 30 min, the p-STAT3 level reached the peak and showed nuclear
      translocation of p-STAT3 from the cytoplasm to the nucleus. These effects could
      be overcome by a small peptide (ATWLPPR) specific for VEGFR2. Taken together,
      VEGF-induced phosphorylation and nuclear translocation of STAT3 and ATWLPPR could
      effectively block the VEGF effects, suggesting that phosphorylation of STAT3
      participates in VEGF signal transduction via VEGFR2 in ovarian carcinoma cells.

PMID- 17009628
TI  - Potential role of preoperative serum CA125 for the differential diagnosis between
      uterine leiomyoma and uterine leiomyosarcoma.
AB  - PURPOSE: Most comparisons between uterine leiomyoma and uterine leiomyosarcoma
      have been based on postoperative pathological or molecular analyses. Very few
      reports have investigated preoperative differentiation between uterine leiomyoma
      and uterine leiomyosarcoma. METHODS: Between January 1990 and December 2003, 42
      consecutive patients with uterine leiomyosarcoma treated at index hospitals were
      analyzed. Meanwhile, 84 patients with uterine leiomyomas were used as controls.
      The diagnostic performance of preoperative serum CA125 for the differential
      diagnosis between uterine leiomyoma and uterine leiomyosarcoma using receiver
      operating characteristic (ROC) curves was evaluated. Data presentations were
      categorized into premenopausal and postmenopausal groups. Diagnostic efficiency
      was calculated as the sensitivity multiplied by the specificity. RESULTS: Values
      of preoperative serum CA125 were significantly higher in the uterine
      leiomyosarcoma group than those in the uterine leiomyoma group. There was
      significant overlapping of preoperative serum CA125 between the uterine leiomyoma
      group and early-stage uterine leiomyosarcoma. For both the premenopausal and
      postmenopausal group, there was a significant difference in the distribution of
      preoperative serum CA125 in early-stage and advanced-stage uterine
      leiomyosarcoma. The optimal cutoff values of serum CA125 for the premenopausal
      group and postmenopausal group was 162 U/mL and 75 U/mL, respectively.
      CONCLUSION: These findings demonstrated that preoperative serum CA125 had a
      potential role in the differential diagnosis between early-stage and advanced
      stage uterine leiomyosarcoma. Further investigation with a larger sample size at
      adequate power is necessary to verify the current study.

PMID- 17009629
TI  - Does shifting a physician payment system shift physician priorities? A multi-site
      evaluation of an alternative payment plan (APP) for gynecologic oncologists in
      Ontario.
AB  - OBJECTIVE: The objective of this study was to attempt to understand how changing
      the mode of reimbursement alters physician behavior from the physician's
      perspective. METHOD: Individual interviews were conducted with 14 Ontario
      gynecologic oncologists. Each interview was analyzed using grounded theory.
      RESULTS: The move to an alternative payment plan (APP) significantly shifted
      physician clinical and personal priorities. This resulted in improvements in
      recruitment and retention. A model was developed to explain the link between the
      shift in the payment system and physician perceptions of their behavior. The
      model is comprised of two themes: (a) need for change: site similarities and
      differences, (b) effects of change: shifting priorities and time management. Even
      when the same compensation package was offered to four sites, the interpretations
      and motivations differed from site to site. We identified two types of
      situations: sites that were operating in 'survival mode' and those that were
      'meeting core clinical and academic requirements'. They experienced the APP very
      differently. CONCLUSION: This study presents a model that depicts how and why a
      funding shift has variable effects on physician behaviors, depending on the
      individual physician, site, and multi-site perspectives. It offers one of the few
      qualitative evaluations of a funding change.

PMID- 17009630
TI  - Studies on leptin and leptin receptor gene expression in myometrium and uterine
      myomas of gnRH analogue-treated women.
AB  - AIM: To test if treatment with GnRH analogue, which leads to a significant
      reduction in myoma volume, changes expression of leptin genes and gene coding
      leptin receptor isoforms in uterine myomas and in the surrounding unaltered
      myometrium. METHODS: Using RT-PCR, expression of leptin genes and leptin receptor
      genes was studied in myomas and in the surrounding myometrium in women with
      uterine myomas, untreated or treated with GnRH analogue. In the randomly selected
      cases presence of leptin protein and of leptin receptor proteins was examined
      also by Western blotting. RESULTS: Expression of leptin genes was demonstrated
      both in myomas and in the surrounding myometrium, and a similar pattern of
      expression was found for leptin receptor isoforms. The results of RT-PCR were
      confirmed by Western blotting, which documented the identical distribution of
      leptin proteins and leptin receptor proteins in studied tissues. Treatment with
      GnRH analogue had no effect on the expression pattern of studied genes.
      CONCLUSION: The results of the present study on the administration of GnRH
      analogue to females with myomas suggest that no direct or immediate inter
      relationship exists between expression of leptin genes in uterine myomas on one
      hand and estrogen, progesterone and leptin levels in the blood on the other.
      Expression seems to be of a more durable nature but factors that induce such
      expression remain unknown.

PMID- 17009631
TI  - A therapeutic algorithm for early-stage endometrial cancer: indications, patient
      selection, and feasibility.
AB  - Endometrial cancer is the most widely spread gynaecologic neoplasm in industrial
      countries. Mode of spread includes direct extension, lymphatic and haematic
      diffusion. Lymphatic involvement, particularly, is a topic of wide debate due to
      the strong therapeutic implications associated with it. In this regard, anatomic
      surgical staging is better in that it corresponds to real conditions whereas
      clinical-instrumental staging is still today incomplete.

PMID- 17009632
TI  - Immunohistochemical evaluation of PTEN protein in patients with endometrial
      intraepithelial neoplasia compared to endometrial adenocarcinoma and
      proliferative phase endometrium.
AB  - OBJECTIVE: The aim of this study was to reclassify endometrial hyperplasia cases
      and examine PTEN protein immunoreactivity compared to cases with endometrial
      adenocarcinoma and proliferative endometrium. DESIGN: Endometrial samples from 37
      women with endometrial hyperplasia with atypia were reclassified as endometrial
      intraepithelial neoplasia (EIN). Eighteen were complex and 19 were simple
      endometrial hyperplasia. Twenty-our cases of EIN, ten endometrial adenocarcinoma
      cases and ten proliferative phase endometrium sections were immunostained for
      PTEN expression. PTEN expression was documented according to the degree of
      immunoreactivity as complete loss, partial loss and present. RESULTS: Twenty-four
      of 37 (64%) women with endometrial hyperplasia were reclassified as EIN. Complete
      loss of PTEN immunoreactivity was found in only one of the 24 EIN patients
      (4.2%), partial loss in eight of 24 (33.3%) and present in 15 of 24 (62.5%).
      There were no difference in PTEN immunoreactivity between EIN, endometrial
      adenocarcinoma and endometrial proliferation (p = 0.342). PTEN immunoreactivity
      was partially lost in seven and present in three of the patients with endometrial
      adenocarcinoma. None of the patients expressed complete loss of PTEN
      immunoreactivity in this group. CONCLUSION: EIN classification may provide a
      better and more objective assessment of endometrial hyperplasia cases. PTEN
      expression showed no differences among the cases of EIN, endometrial carcinoma
      and proliferative phase endometrium.

PMID- 17009633
TI  - Is dosage of hormone replacement therapy related with endometrial polyp
      formation?
AB  - PURPOSE OF INVESTIGATION: To evaluate the effect of different doses of hormone
      replacement therapy (HRT) on endometrial polyp formation. METHODS: 398 menopausal
      women were initially evaluated through transvaginal ultrasound and patients who
      already had endometrial polyps were excluded from the study. One hundred and six
      (26.6%) eligible patients were enrolled and randomized into two groups of 53
      patients to receive two different doses of HRT. RESULTS: Six patients with
      endometrial polyps were detected in the first group and one patient in the second
      one (p = 0.0502 for total chi-square and p = .1172 for chi-square with continuity
      correction) after a mean duration of treatment of 26 months and 28,5 months,
      respectively. There was no difference in the mean number or the mean volume of
      the polyps between the two subgroups with positive results. CONCLUSION: Our study
      showed that endometrial polyp formation may be related with HRT dosage.

PMID- 17009634
TI  - Primary yolk sac tumor (endodermal sinus tumor) of the vulva: case report and
      review of the literature.
AB  - INTRODUCTION: Endodermal sinus tumor (EST) or primary yolk sac tumor (YST) of the
      vulva is extremely rare and a highly malignant germ cell tumor. Only nine cases
      of vulvar YST have been reported to the world literature to date. We present the
      tenth case of endodermal sinus tumor of the vulva. CASE: A 32-year-old white
      virgin presented with a 3.5 cm right labial mass without any other signs or
      symptoms. Excisional biopsy showed YST with a predominantly solid pattern.
      Unilateral hemivulvectomy with bilateral inguinal lymphadenectomy was performed.
      Six months after surgery there was a recurrence. She was treated with three
      courses of the BEP regimen (bleomycin, etoposide, cisplatin). The patient refused
      to take any further treatment including radiotherapy. The serum alpha-fetoprotein
      (AFP) was not elevated at the initial diagnosis however it was elevated during
      recurrence. The patient is alive with the disease 42 months after the first
      appearance of the vulvar mass.

PMID- 17009635
TI  - Women younger than 50 years with endometrial cancer.
AB  - PURPOSE OF INVESTIGATION: The purpose of the study was to evaluate if known risk
      factors for endometrial cancer in menopausal women are also related to
      endometrial cancer in younger ages. METHODS: Eighty-one patients with a mean age
      of 46.3 years diagnosed with endometrial cancer (EC) (histologically confirmed)
      from January of 1992 to December of 2004 were included in the study. The EC group
      of patients was compared with 100 patients (control group) randomly selected from
      the gynecologic clinic (inclusion criteria: age 43-48 years) without any
      endometrial cancer diagnoses that were evaluated for the same factors. RESULTS:
      Mean BMI was 34.4 kg/m2 (SD = 8.8) in the first group and 28.3 (SD = 7.6) in the
      second one (p < 0.001). None of the women in the EC group reported any history of
      oral contraception. With the exception of hypertension and ovarian cancer
      (probably related to small numbers) all other comparisons were statistically
      significant (although some only marginally). DISCUSSION: From the results of our
      study, it seems that body mass index (BMI), parity, type of menstrual cycles,
      history of polycystic ovarian (PCO) syndrome and diabetes are possibly related to
      endometrial cancer in women younger than 50 years of age, and the strongest
      relation was found with increased BMI. Also, there was no increased incidence of
      hypertensive disease in the EC group. CONCLUSION: Prospective studies are needed
      for final conclusions.

PMID- 17009636
TI  - Impact of morbid obesity in surgical management of endometrial cancer: surgical
      morbidity, clinical and pathological aspects.
AB  - OBJECTIVE: To evaluate the effect of body mass index (BMI) on clinical, surgical,
      pathologic features, and surgical morbidity in the management of patients with
      endometrial cancer. MATERIALS & METHODS: All endometrial cancer patients who were
      surgically treated in our institution between January 1, 2003 and January 1, 2006
      were eligible for the study. Forty-two out of 60 patients were included in the
      analysis from our cancer database. The patients were divided into three groups:
      BMI < 30, BMI 30-40, BMI > 40. Statistical analysis was performed by SPSS for
      Windows (version 11; SPSS, Inc., Chicago, IL). RESULTS: Lymphadenectomy as part
      of surgical staging was performed in 90.5% of all patients. Although patients
      with a BMI > 40 were less likely to have positive lymph vascular space invasion
      (LVSI) (p = 0.042), chance of deep myometrial invasion and positive lymph nodes
      (18%) were the same as for patients with a BMI < 30. Patients with a BMI > 40 had
      statistically longer operating times when compared to patients with a BMI < 40 (p
      = 0.039). Wound separation rate was statistically higher in the morbidly obese
      patients (p = 0.01). Average number of lymph nodes removed, hospital days,
      intraoperative and overall postoperative complication rates did not differ among
      the three groups (p > 0.05). CONCLUSIONS: This study confirms that comprehensive
      surgical staging can be performed adequately and safely in obese and morbidly
      obese endometrial cancer patients with no difference in length of hospital stay,
      intraoperative or postoperative complications. As a result adjuvant treatment of
      morbidly obese patients can be planned accordingly preventing under or over
      treatment.

PMID- 17009637
TI  - Chlamydia trachomatis and herpes simplex virus 2 infection in vulvar
      intraepithelial neoplasia associated with human papillomavirus.
AB  - BACKGROUND: The role of viral and bacterial co-infection is stressed in VIN. A
      view that VIN is a sexually transmitted disease made the area of research larger
      and stimulated scientists to seek other sexually transmitted factors, among which
      Chlamydia trachomatis and Herpes simplex are frequently examined. PURPOSE: The
      aim of the study was to evaluate the frequency of occurrence of HPV DNA and the
      frequency of co-infection with Herpes virus type 2 and Chlamydia trachomatis in
      VIN. MATERIAL AND METHODS: We identified archival diagnostic phase tissue
      specimens from 41 cases of vulvar intraepithelial neoplasia III. From the same
      paraffin blocks containing material from the margins of surgical sections during
      vulvectomy, normal epithelial tissue fragments were collected. They constituted
      the control group. Lesion characteristics were examined in comparison with the
      presence of HPV DNA, HSV-2 and Chlamydia trachomatsis. Identification was
      performed using PCR. RESULTS: In the study group HPV infection was found in 75.6%
      of cases. In 73% of cases it was HPV 16. In the control group we found HPV 16 DNA
      in only one case (2.43%). In the HPV positive study group HPV 16 was found in 30
      (30/31) cases. In only one case (1/31) it was HPV 18 type. In the study group of
      41 cases with VIN, HSV-2 infection was found in six cases (14.63%). In comparison
      with the control group (9.75%) the difference was not statistically significant.
      The frequency of occurrence of Chlamydia trachomatis in the analyzed study
      material was 14.63% (6/41) and in the control group it was 9.75% (4/41). The
      difference was not statistically significant. Statistical analyses of
      correlations between the occurrence of DNA HPV and HSV-2 as well as of HPV and
      Chlamydia trachomatis showed no correlation in either case. CONCLUSION: No
      correlation was found between the frequency of occurrence of HPV and HSV-2 and
      HPV and Chlamydia trachomatis in either group.

PMID- 17009638
TI  - Endometrial carcinoma and hormonal disturbances in middle-aged women--an
      overview.
AB  - Endometrial hyperplasias and endometrial adenocarcinomas present a morphological
      continuity. In 1,150 cases of patients admitted to two hospitals over the past
      two years with diagnosed irregular bleeding, suspected ultrasonography findings
      and positive family history, we performed, not only hormonal examinations, but
      also fractioned explorative curettage after receiving patient consent.

PMID- 17009639
TI  - Receptor modifications in vulvar dystrophies before and after treatment with
      topical hormones: comparison between the dextran-charcoal technique and
      immunohistochemical evaluation.
AB  - PURPOSE OF INVESTIGATION: The objective of the study was first to quantify
      estrogen receptors (ERs) and progesterone receptors (PRs) in dystrophic vulvar
      tissue before and after topical hormone treatment in an attempt to evaluate
      whether receptor modifications occurred. Second we compared quantitative analysis
      with immunohistochemical staining of the vulvar specimens. METHODS: We studied
      115 vulvar specimens obtained from 75 consenting women ranging from 21 to 78
      years of age. Of the patients, 12 had histologically normal vulvar skin, 45 had
      vulvar dystrophies that were not treated by topical steroid therapy, 28 patients
      had vulvar dystrophies that were treated by testosterone propionate (TP) 2%, 12
      patients had vulvar dystrophies that were treated by progesterone in
      hydroalcoholic gel and 18 patients had vulvar malignant tumors. For
      immunohistochemical analysis we considered 25 cases of vulvar dystrophies: 11
      cases of squamous hyperplasia (SH) and 14 cases of lichen sclerosus (LS). Among
      these 25 cases, 15 (5 SH and 10 LS) were treated with TP 2%. RESULTS: After
      treatment of the vulvar dystrophies with progesterone, the positivity of ERs
      decreased (58.3% vs 77.8%). After treatment of the vulvar dystrophies with TP 2%,
      the positivity of PRs significantly decreased (14.3% vs 68.9%) whereas after
      treatment with progesterone the positivity of PRs increased (83.3%). The
      immunohistochemical study showed some differences in comparison to the
      quantitative study. In fact we found low basal positivity especially for PRs (16%
      vs 68.9% of the quantitative study). This finding was due to the use of a cutoff
      of at least ++ in order to increase the specificity. After treatment with TP 2%,
      we observed an increase of immunohistochemical positivity for ERs even in cases
      that were negative before treatment and a lack of PRs even in cases that were
      positive before treatment. CONCLUSIONS: These data demonstrate the efficacy of
      androgen therapy with TP 2% in vulvar dystrophies with increased trophism due to
      the increase of ERs.

PMID- 17009640
TI  - The management of ectopic breast cancer--case report.
AB  - Ectopic breast tissue occurs when the mammary ridge fails to resolve during
      embryonic development. Ectopic breasts, either supernumerary or aberrant, have an
      incidence of 6%. Ectopic breast tissue is however hardly mentioned in the
      literature. Also benign and malignant alterations in these "breasts" are under
      reported. The lifetime risk of women being diagnosed with breast cancer is 13%.
      It should be recommended that these "breasts" be included in the screening. Due
      to the unawareness this is generally not happening. The present article describes
      a case of ectopic breast cancer and discusses therapeutic management. A
      subcutaneous mass along the 'milk line' should be examined carefully and any
      suspicious lesions should be approached according to the guidelines for the
      management of symptomatic breast disease. Ipsilateral prophylactic mastectomy has
      no role in the management of a single ectopic breast cancer tissue.

PMID- 17009641
TI  - Serous cystadenoma of borderline malignancy arising in a parovarian
      paramesonephric cyst.
AB  - BACKGROUND: Borderline parovarian tumors are found incidentally at surgery or
      autopsy. They are extremely rare. The majority have been reported in young women
      and rarely are they large enough to be clinically significant. CASE: A 53-year
      old multiparous female with a symptomatic paraovarian serous borderline
      cystadenoma is presented. DISCUSSION: The clinical aspects and subsequent
      management of related cases are discussed.

PMID- 17009642
TI  - A case of cellulitis that complicated lymphedema of the lower limb and produced
      systemic inflammatory response syndrome (SIRS).
AB  - This is the first report describing lymphedema of the lower limb after surgery
      for ovarian cancer complicated by severe cellulitis with systemic inflammatory
      response syndrome (SIRS). Debridement of the lesion and a split-thickness graft
      were required for a complete cure. Although lymphedema as a complication after
      surgery for gynecologic malignancies is prone to be considered less serious on
      the medical side, it is considered necessary to treat lymphedema of the lower
      limbs while it is still in a mild state since severe cellulitis may accompany
      lymphedema, as in the present case.

PMID- 17009643
TI  - Colorectal cancer emergencies during pregnancy case reports.
AB  - Colorectal carcinoma emergencies during pregnancy are exceptionally rare. Three
      women 38, 31 and 36 years old, in the third trimester of gestation received
      treatment, respectively, for acute abdomen due to perforation of rectal
      carcinoma, ileus due to a sigmoid tumor, and deep venous thrombosis (DVT) from a
      cecal tumor compromising the right iliac vein. In the first two patients urgent
      cesarean sections were carried out with Hartmann's procedure and a loop colostomy
      was performed to resolve the ensuing intraabdominal sepsis and ileus,
      respectively. In the third patient, a cesarean section was carried out to treat
      the underlying DVT more aggressively, while right colectomy was postponed for
      three weeks. Restoration of the alimentary tract was achieved two months later in
      the first case, while in the second and third cases total colectomy due to
      familial polyposis and right colectomy were performed three weeks after the
      cesarean section. An overview of the clinical features, diagnostic pitfalls and
      therapeutic approaches to manage complications of colorectal cancer during
      pregnancy are discussed.

PMID- 17009645
TI  - Abdominal apoplexy associated with the levonorgestrel intrauterine system--case
      report.
AB  - Abdominal apoplexy is defined as intraabdominal haemorrhage without an
      identifiable pathology. This life-threatening situation is hardly mentioned in
      the literature. The clinical tableau is non-specific. The onset can be with
      nausea, mild to severe abdominal pain, a palpable mass in the abdomen or flank
      and sings of hypovolemic shock. The approach should be resuscitation, look for a
      likely underlying cause and control the bleeding. The present report will
      describe a case of abdominal apoplexy in a patient using a levonorgestrel
      intrauterine system. The management and possible origins of abdominal apoplexy
      will be discussed.

PMID- 17009644
TI  - Synchronous primary cancers of the endometrium and ovary: a case report.
AB  - Synchronous primary cancers of the endometrium and ovary are found in 5% of women
      with endometrial cancer and 10% of women with ovarian cancer. In the present
      case, a multigravid 46-year-old woman complained of lower abdominal pain and
      abdominal distension. She did not define abnormal uterine bleeding. Screening
      ultrasound revealed a papillary containing structure, irregular, cystic 16 x 15 x
      10 cm right ovarian mass. Preoperative endometrial biopsy revealed endometrioid
      adenocarcinoma. Ascites sampling, radical hysterectomy, bilateral salpingo
      oophorectomy, pelvic and paraaortic lymphadenectomy, omentectomy, appendectomy
      and cytologic sampling of the undersurface of the diaphragm were carried out.
      Intraoperative and histological examinations showed Stage IIIC papillary serous
      carcinoma and stage IC endometrioid adenocarcinoma. Synchronous genital tract
      neoplasms constitute a more common clinical problem than would generally be
      expected.

PMID- 17009646
TI  - Endometrial adenocarcinoma after endometrial ablation. A case report.
AB  - The authors present a case of endometrial adenocarcinoma after endometrial
      ablation, emphasizing the importance of close surveillance of these patients,
      patient selection and education. Even patients with none of the risk factors for
      endometrial cancer or contraindications to endometrial ablation should be checked
      carefully.

PMID- 17009647
TI  - Synchronous primary endometrial and ovarian cancers: a case report.
AB  - Synchronous primary cancers of the endometrium and ovary are relatively uncommon
      in the general population. The patient, a 49-year-old postmenopausal Greek woman,
      presented with abdominal pain and a pelvic mass. She underwent total abdominal
      hysterectomy with bilateral salpingo-oophorectomy, total omentectomy,
      appendectomy and pelvic lymph node dissection. The histopathology revealed
      synchronous primary cancers of the endometrium and right ovary. She underwent
      postoperative chemotherapy. Thirty-nine months after surgery, she remains well
      without evidence of recurrence.

PMID- 17009648
TI  - Pharmacokinetic analysis of paclitaxel and carboplatin in a patient with advanced
      ovarian cancer during hemodialysis--case report.
AB  - We examined pharmacokinetics of paclitaxel and carboplatin in a FIGO Stage IIIb
      ovarian cancer patient with hemodialysis-dependent chronic renal failure. The
      patient suffered from recurrence of the disease after treatment with optimal
      debulking surgery and postoperative chemotherapy consisting of cisplatin,
      epirubicin and cyclophosphamide, and she was treated with combined paclitaxel and
      carboplatin as second-line chemotherapy. The carboplatin dose was chosen to
      produce a target area under the concentration/time curve (AUC) of 5.0 microg
      min/ml according to a published formula. Four-hour hemodialysis was started 24
      hours and 16 hours after the end of carboplatin administration in the first and
      second courses of the chemotherapy, respectively. Pharmacokinetic studies showed
      that the AUCs of free platinum were 8.03 and 5.69 microg-min/ml in the first and
      second courses of the chemotherapy, respectively, suggesting that the AUC of
      carboplatin is affected by hemodialysis. However, an attenuation pattern of
      paclitaxel was almost similar between the first and the second courses,
      indicating that the change in blood concentration of paclitaxel was similar to
      that of patients with normal renal function. Hematological and nonhematological
      adverse effects were at an acceptable degree. The evidence suggests that even
      patients with chronic renal failure can undergo combination chemotherapy of
      paclitaxel and carboplatin without suffering any severe adverse effects by
      determining the time to start hemodialysis.

PMID- 17009649
TI  - Sentinel node biopsy helps to diagnose spread of endometrial cancer. A case
      report.
AB  - BACKGROUND: The sentinel lymph node (SLN) could improve the staging of
      endometrial cancer. CASE: In a patient with endometrial cancer, preoperative
      lymphoscintigraphy showed a highly radioactive SLN in the left external iliac
      chain and a radioactive SLN in the right external iliac chain and at the
      promontory. Intraoperative lymphatic mapping using blue dye and a hand-held gamma
      probe showed the same nodes, as well as a blue node near the vena cava. Selective
      removal of these nodes allowed detection of a micrometastasis in the left
      external iliac node. Pelvic node dissection was performed, and a micrometastasis
      was found in a left non sentinel iliac node. CONCLUSION: The presence in our
      patient of micrometastases in a SLN and in a non-SLN belonging to the same chain
      confirms the value of SLN detection for diagnosing tumor spread.

PMID- 17009650
TI  - Solitary ovarian metastasis from cutaneous melanoma--case report.
AB  - A 47-year-old patient with two previous deliveries and three deliberate abortions
      was admitted to the Institute of Gynecology and Obstetrics, Clinical Center of
      Serbia with the diagnosis of a uterine myoma and left adnexal mass. Five years
      previously, she had undergone excision of a malignant melanoma from her left leg.
      Pelvic exemination disclosed a left adnexal solid mass measuring about 100 x 80 x
      80 mm and enlarged uterus 120 x 50 mm in size with myomatosus nodes on the
      posterior wall. After ultrasound and computed tomography examination, the patient
      underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy,
      intracolic omentectomy and selective pelvic lymphonodectomy. The final
      histopathological diagnosis was metastatic amelanotic malignant melanoma of the
      left ovary and uterine myomas. After surgery the patient was transferred to the
      Institute of Oncology and Radiology where she received chemotherapy.

PMID- 17009651
TI  - Analyzing disavowed action: the fundamental resistance of analysis.
AB  - Several detailed analytic hours illustrate how, with the analyst's full
      participation, patients use the words, setting, and activity of analysis to
      gratify the very wishes they are analyzing, and so disavow the work of analysis.
      These gratifications, which are hidden in plain sight, are themselves disavowed
      in the apparent pursuit of analytic understanding. In this way the patient's and
      the analyst's use of the analytic situation becomes the fundamental resistance to
      the work itself. This process shares features in common with perversion. The
      painful but necessary task for both analyst and patient is to analyze this
      process as it is occurring, moment by moment, in the real time of the hour.

PMID- 17009652
TI  - Mind, madness, and medications: situating psychoanalysis.

PMID- 17009653
TI  - Talking about medication.
AB  - With the increasing use of psychotropic medication concomitant with
      psychoanalysis, attention must be given to the challenges created by complaints
      of medication side effects. When confronted with these side effects, analysts may
      experience specific, uniquely actualized countertransference anxieties that can
      prompt the abandonment of transference analysis. Particular countertransference
      fantasies that arise in combined treatments are examined, as are the reasons for
      the analyst's suspension of curiosity and openness and its clinical consequences.
      In these situations, effective analysis requires the analyst to be "bilingual,"
      to hold in mind both the analytic and the pharmacological model.

PMID- 17009654
TI  - Thoughts on medication and psychoanalysis: a lay analyst's view.
AB  - The issues involved in split analytic treatments-where a second person manages
      the patient's medication-are discussed from the point of view of a
      developmentalist and lay analyst. Case material is presented to illustrate the
      interplay of medication with other elements of the psychoanalytic situation.
      Medication and its effects, it is argued, should be accorded no special status
      apart from other interventions and enactments in an analysis. Some see medication
      and psychoanalysis as parallel processes, two separate and unintegrated
      theoretical systems, and recommend shifting back and forth between models of the
      mind or becoming "bilingual"; against this view, it is argued that anything the
      analyst does will affect the patient's thoughts, fantasies, and even physiology
      in individual ways, and only attention to analytic material can reveal what an
      intervention means in a specific case. Success in split treatment depends on a
      collaborative therapeutic alliance among patient, analyst, and consultant.
      Because there is as yet no theory that bridges psychoanalysis and
      psychopharmacology, analysts must talk of these matters as incompletely
      synthesized and regard them as part of the challenges that make psychoanalysis
      the exciting, impossible profession it is.

PMID- 17009655
TI  - Medication as object.
AB  - People experience and treat medication as though it were a person: in other
      words, as an object. Among the many symbolic meanings attributed to medication,
      this sort of personification, or object representation, is a meaning that
      medication is uniquely positioned to contain and convey: imbued with
      intentionality and influence, medication moves beyond the sphere of static,
      iconic representation and enters the changeable, dynamic object world of action,
      aim, and agency. Unlike more generic or stereotypic meanings, object
      representations attributed to medication may reflect the patient's specific
      dynamics and object relations. These representations are many and mutable, and
      take on shifting and overlapping forms that evolve with the analytic process.
      Medication may represent a third person within the framework of an analytic
      treatment, expanding the analytic dyad into a triad and offering new transference
      paradigms to explore. The defensive displacement of transferential qualities and
      attitudes, or split-off parts thereof, from the analyst onto medication can serve
      as a powerful resistance to the awareness of the transference to the analyst.
      Clinical examples illustrate the utility and importance of the analysis of
      medication as object, for both patient and analyst, with particular attention to
      the transference.

PMID- 17009656
TI  - Learning about psychoanalysis combined with medication: a nonphysician's
      perspective.
AB  - When medication is at play in an analysis, the nonphysician candidate or
      psychoanalyst faces conceptual and practical challenges, as well as
      countertransference risks and opportunities. A psychologist psychoanalytic
      candidate describes the treatment of an analysand who underwent a gradual
      uncovering and worsening of obsessive-compulsive and anxiety symptoms; at twenty
      one months, the analysand introduced the topic of medication. These developments
      brought to light transference and countertransference themes connected to the
      analyst's status as a non-physician candidate; conceptual and practical
      uncertainties about medication in the context of psychoanalysis; the complex
      meanings of, and indications for, medication in this case; and the ramifications
      of a nonphysician candidate's referring a patient to a psychiatrist psychoanalyst
      for medication while being supervised by another psychiatrist psychoanalyst.

PMID- 17009657
TI  - Psychoanalysis in conjunction with medication: a clinical research opportunity.
AB  - The increasingly common practice of introducing medication into the analytic
      relationship is of practical and theoretical concern to analysts. Pharmacological
      agents and their somatic effects, it is argued, may be seen as a research
      equivalent to brain lesions, long favored tools in correlating brain with mind
      function, while psychoanalytic process data may be seen as a fine-tuned
      instrument for studying the subjective and emotional processes that reflect the
      underlying brain effect. A method of naturalistic study of psychoanalytic process
      both with and without a psychopharmacological agent is described and illustrated
      in two patients. The potential of this method for providing data useful in
      understanding the mechanism of action of psychoactive medications and of
      individual variations in response is explored. Both patients, treated with
      stimulant for ADHD, showed striking differences in self- and object
      representation, defense, affect, and cognition that correlated with analytic
      periods on and off the medication. The implications of these observations for
      understanding both the action of the medication and the fundamental functional
      disruptions in the condition are explored as well.

PMID- 17009658
TI  - Interdisciplinary studies and our practice.
AB  - Why should psychoanalysts learn about neighboring disciplines? It is often argued
      that, although information from neuroscience, neuropsychology, evolutionary
      psychology, and other fields may be of interest to analysts, it has no real
      effect on their practice: on the way they listen, the way they react, or the way
      they treat their patients. A corollary of this position is that there is no
      reason to include such information in a psychoanalytic curriculum, since it does
      not help candidates become better analysts. Against this view, two reasons are
      advanced for the importance of interdisciplinary study. The more general reason
      is that it grounds psychoanalysis in the broader scientific world, reducing its
      isolation and inbred parochialism. This can help justify the discipline
      intellectually, possibly in advance of and independently of supportive research
      from within the field (e.g., outcome studies). The second reason is that our own
      minds, and particularly those of the generation now entering training, have been
      altered by changes in the scientific zeitgeist and we need to have some grasp of
      these changes. Finally, six examples of findings from other disciplines are
      presented that even now may be contributing to thinking about psychoanalytic
      practice.

PMID- 17009659
TI  - From developmental metaphor to developmental model: the shrinking role of
      language in the talking cure.
AB  - Psychoanalysts have invoked infant development diversely to understand nonverbal
      and unspoken aspects of lived experience. Two uses of developmental notions and
      their implications for understanding language and the therapeutic action of
      psychoanalysis are juxtaposed here: Hans Loewald's conception of developmental
      metaphors to illuminate ineffable aspects of the clinical situation and Daniel
      Stern's currently popular developmental model, which draws on findings from
      quantitative research to explain therapeutic action in the nonverbal realm.
      Loewald's metaphorical use of early development identifies and thus potentiates a
      central role for language in psychoanalytic treatment. By contrast, Stern and his
      colleagues exaggerate the abstract, orderly, and disembodied qualities of
      language, and consequently underestimate the degree to which lived interpersonal
      experience can be meaningfully verbalized, as demonstrated here with
      illustrations from published clinical material. As contemporary psychoanalysis
      moves toward embracing developmental models such as Stern's, it is concluded,
      psychoanalysts accept a shrinking role for language in the talking cure.

PMID- 17009660
TI  - What's in a name: what analyst and patient call each other.
AB  - Awkward moments often arise between patient and analyst involving the question,
      "What do we call each other?" The manner in which the dyad address each other
      contains material central to the patient's inner life. Names, like dreams,
      deserve a privileged status as providing a royal road into the paradoxical
      analytic relationship and the unconscious conflicts that feed it. Whether an
      analyst addresses the patient formally, informally, or not at all, awareness of
      the issues surrounding names is important.

PMID- 17009661
TI  - The absence of a future: the effect of past experience and current developmental
      conflicts on a midlife analysis.
AB  - The four-year analysis of Mr. T, a highly intelligent, successful professional
      who entered analysis primarily because of a depression is presented; he had had
      no previous therapeutic experience but was very curious about analysis. The
      analytic work led to the discovery of a deeply held unconscious conviction of
      premature death that was related to interaction among the effects of a traumatic
      parental divorce during childhood, estrangement from both parents prior to their
      deaths, and signs of aging and illness in midlife. Before this analytic work the
      patient was unable to conceptualize, let alone plan for, late-life developmental
      experiences such as retirement and grandparenthood. Transference
      countertransference themes are discussed, as is the importance of an
      understanding of midlife developmental concepts to successful analytic work with
      patients in this age group.

PMID- 17009662
TI  - Friedman's corpus since his anatomy: a psychoanalytic odyssey.
AB  - Lawrence Friedman is a preeminent theorist, critic, and commentator in American
      psychoanalysis today. The major themes of his work, beginning with his magnum
      opus, The Anatomy of Psychotherapy (1988), are examined in an effort to identify
      conceptual shifts and problems in contemporary psychoanalysis. In the years since
      publication of that work, Friedman's texts have increasingly focused on the
      epistemological controversies faced by contemporary psychoanalysts. He has become
      a vocal critic of recent developments in relational psychoanalysis, advancing
      views that are explored here and subjected to critical appraisal. To better
      understand Friedman's ideas, areas of disagreement with other authors, including
      Schafer, Renik, Hoffman, Mitchell, Rorty, and Michels, are explored. Finally,
      Friedman is presented as a crypto-intersubjectivist whose work effects a
      realignment of theory with practice.

PMID- 17009663
TI  - Terror and societal regression: does psychoanalysis offer insights for
      international relations? Panel report.

PMID- 17009664
TI  - Wisconsin's caps on noneconomic damages in medical malpractice cases: where
      Wisconsin stands (and should stand) on "tort reform".

PMID- 17009665
TI  - [Experience of a centre for the study of occupational adjustment disorders
      referred to psychological harassment-related diseases at the workplace].
AB  - BACKGROUND: The rising awareness of psychological harassment at the workplace
      means that it is ever more important to collect clinical data and test tools to
      assess psychiatric disease connected with this phenomenon. OBJECTIVES: The aim of
      the study was to assess the experience gained by the centre for work
      maladjustment of the University Hospital of Pisa on a sample of patients, using
      the methods proposed by the centre at the Clinica del Lavoro "Luigi Devoto".
      MATERIALS AND METHODS: The patients were submitted to a diagnostic protocol
      consisting of work history, medical examination, psychological assessment,
      psychiatric examination, subjective questionnaires, mood scale and Neutest. The
      analysis was made in two phases in which 109 subjects were examined to check
      occupational stress effects in the period March 2002 - July 2004, after which 50
      subjects were selected (45.9%) with the adaptation disorder and a history of
      adverse working conditions. RESULTS: The data gathered showed a slight
      predominance of workers from the public administration sector. The most
      representative range of duration of the psychological violence varied from 6
      months to 2 years (46%). From close examination of the causes of the
      maladjustment disorders, structural changes in organization appeared to be the
      most frequent (13 cases). Among patients with positive diagnosis of disorder
      caused by psychological violence at the workplace, three situations were
      prominent: attitude to being a social outcast, behaviour to ignore proposals, and
      professional declassing. CONCLUSIONS: The multidisciplinary approach was
      culturally very stimulating and fundamental in reaching a final diagnosis of
      occupational disease: diagnosis of bullying at work and related disease was
      possible only thanks to the fact that three specialists agreed on the
      aetiological role of psychological harassment at the workplace. Our experience
      confirms that psychological harassment can cause health impairment and the most
      common diagnosis is maladjustment disorder.

PMID- 17009666
TI  - Evaluation of obesity in healthcare workers.
AB  - BACKGROUND: Obesity is an international social problem. OBJECTIVES: This study
      was aimed at evaluating the relationship of overweight and obesity with social
      dynamics and correlated biological indicators. SUBJECTS AND METHODS: The study
      was carried out on a group of healthcare workers employed in a large hospital in
      the province of Messina (Sicily, Italy). A total of 1010 subjects (377 men and
      633 women) aged between 16 and 64 years, living in the province of Messina since
      birth. The educational level, BMI (Body mass index), arterial blood pressure and
      ECG of each subject was examined. RESULTS: The results showed that 52% of the men
      and 66.5% of the women were of normal weight, while the men showed greater
      susceptibility to overweight (M 33.2% > F 16%). Obesity was found in both sexes
      (M 13.3%, F 13.6%). Moreover, it was observed that arterial blood pressure tends
      to increase with age and body weight, and that the incidence of overweight falls
      as educational level rises. CONCLUSIONS: The study supports the hypothesis that
      there is a growing incidence of overweight and obesity in subjects of working age
      employed in the healthcare sector.

PMID- 17009667
TI  - Respiratory findings in art and medical students. Effects of the art environment.
AB  - BACKGROUND: Art students are exposed to many noxious agents during their
      training, in contrast to medical students, who are not exposed to known
      environmental pollutants. OBJECTIVES: In order to investigate the potential
      effects of toxic agents in the art students' environment, we studied respiratory
      findings in a cohort of 117 art students and 128 medical students, matched for
      age, sex and smoking. METHODS: Acute and chronic respiratory symptoms were
      evaluated by modifying the British Medical Research Council questionnaire. Lung
      function studies were performed with a spirometer (Jaeger, Germany) measuring
      maximum expiratory flow-volume (MEFV) curves. On these curves we calculated the
      forced vital capacity (FVC), one second forced expiratory volume (FEV1) and the
      maximal expiratory flow at 50% and the last 25% of the FVC (FEF50, FEF25).
      RESULTS: Significantly higher prevalences of most of the chronic respiratory
      symptoms were recorded in art students compared to medical students (p < 0.05).
      Art students who were smokers had significantly higher prevalences of many of the
      chronic respiratory symptoms than nonsmoking art students. Among medical students
      these differences were not statistically significant (NS). High prevalences of
      acute symptoms related to the study environment were recorded for art students.
      Odds ratios in male and female art students were significant for chronic cough,
      chronic phlegm and chronic bronchitis for the risk factor of smoking.
      Significantly decreased lung function values compared to predicted values were
      recorded mostly for FEF50 and FEF25 in male and female art students. Smoking and
      non-smoking art students had similar reductions of lung function. Lung function
      data in medical students were within predicted values. CONCLUSIONS: Our data
      indicate that art students may be at risk of developing chronic respiratory
      symptoms and lung function changes as a result of their environmental exposure
      and their smoking habits.

PMID- 17009668
TI  - [Longitudinal changes of pulmonary function in workers with high wood dust
      exposure levels].
AB  - BACKGROUND: It is well know that wood dust exposure can induce sino-nasal
      cancers, rhinitis and asthma; induction of chronic bronchial obstruction,
      pulmonary fibrosis and lung cancer are also suggested, but data are often
      inconclusive and in disagreement. OBJECTIVES: The study evaluated the decrease in
      lung function in a group of 31 non-smokers exposed to high levels of wood dust (>
      5 mg/m3 also) and in 2 non-smokering control groups with comparable lung function
      tests at first examination: 39 mechanical workers without respiratory hazards
      (group 1) and 30 forestry workers (group 2). METHODS: Assessment of lung function
      was repeated at least 5 times during 11.2 +/- 2.4 years for wood workers and 12.3
      +/- 4.2 years for group 1 (n.s.) and 15.0 +/- 2.6 years for group 2 (p < 0.0005).
      Linear regression for annual loss of VC and FEV1 was calculated from observed
      data for each subject. RESULTS: No significant differences were observed in VC
      loss or FEV1 loss between woodworkers and control group1 (20.67 +/- 16.9 vs 19.0
      +/- 23.2 and 31.37 +/- 22.3 vs 36.2 +/- 22.4 ml/year respectively), while control
      group 2 showed an accelerated (p < 0.005) VC and FEV1 loss (32.8 +/- 22.1 and
      46.6 +/- 21.2 ml/years respectively). In conclusion, the study did not show any
      alterations in the longitudinal decrease in pulmonary function due to high wood
      dust exposure levels, perhaps due to the poor inhalability of wood particles that
      are mostly trapped in the nose; further studies are needed to investigate chronic
      effects of wood dust exposure on development of Chronic Obstructive Pulmonary
      Disease, pulmonary fibrosis and also lung cancer.

PMID- 17009669
TI  - [Mount Reventino greenstone: assessment of tremolite fibre dispersion in the
      workplace].
AB  - BACKGROUND: Mount Reventino, a massif located in the Calabria Region of Italy,
      has several ophiolite outcrops of greenstone. These deposits are an important
      economical resource in the surrounding area. Some rock layers contain tremolite,
      a type of asbestos fibre. OBJECTIVES: The aim of this paper was to analyze the
      chemical and physical structure of the outcrops of Mount Reventino, and to assess
      and reduce the risk to workers associated with exposure to airborne fibres.
      METHODS: Personal and environmental samples were collected and analysed by
      Scanning Electron Microscopy equipped with energy-dispersive X-ray analysis.
      RESULTS: The analysis of samples showed a difference in mineralogical features
      not only between the quarries under study, but also between the two opposite
      sides of the mountain. Exploitation of the quarries produces a fibre dispersion
      that is higher than the natural emission. Occupational exposure to asbestos
      fibres during greenstone transformation was confirmed by by the results of
      analysis of the collected samples. CONCLUSIONS: This study made it possible to
      identify working activities with highest exposure to asbestos and establish the
      correct procedures to abate fibre dispersion, in order to reduce the correlated
      risk. Environmental samples collected in the urban area surrounding the quarries
      showed that the asbestos fibre concentrations were very low, however, further
      studies are needed in order to confirm these findings.

PMID- 17009670
TI  - Quality of life and smoking among industrial workers in Greece.
AB  - BACKGROUND: Smoking is a predictor of quality of life, while socio-economic
      factors influence the prevalence of smoking habits. Occupational medical research
      has been fairly late in coming to study quality of life aspects in working
      populations. OBJECTIVES: The aim of the study is the assessment of smoking
      prevalence among blue- and white-collar workers industrial workers in Greece and
      its impact on health-related quality of life. METHODS: In a cross-sectional study
      the Euro-Qol 5D questionnaire was been used in a random sample of 472 blue and
      white-collar heavy industry workers. RESULTS: 57% of the study population were
      current smokers. The difference in prevalence of smoking across all the examined
      socio-demographic variables (sex, age, education and occupation) was not
      statistically significant. Smoking had a significant impact on the health-related
      quality of life. Smokers recorded significant lower scores (74.9) in the overall
      Visual Analogue Scale in comparison with non-smokers (79.1), (p = 0.007). Further
      analysis revealed that age, smoking and education were significant predictors of
      VAS score. A non-significant contribution was found for occupation and sex.
      Smokers reported significantly higher rates of problems regarding mobility, self
      care and anxiety/depression than non-smokers. Logistic regression analysis showed
      an independent impact of smoking on mobility, self-care and anxiety/depression
      level. CONCLUSIONS: Smoking is a significant hazard and a strong predictor of
      poor quality of life among the blue- and white-collar workers under study. Anti
      smoking policies integrated into a broader context of occupational health and
      safety at work could reduce smoking rates and thus improve worker's quality of
      life.

PMID- 17009671
TI  - [Pleural mesothelioma in cotton spinning workers].
AB  - BACKGROUND: Cases of malignant mesothelioma (MM) in the non-asbestos textile
      industry have recently been described, but asbestos exposure in spinning and
      looming has seldom been reported. Nevertheless, on a national level the Italian
      Mesothelioma Registry (Re.Na.M) contains numerous cases of MM with past non
      asbestos textile work but classified as "unknown" exposure due to poor
      information. OBJECTIVES: The aim of this research was to investigate possible
      past occupational exposure to asbestos in this specific industrial sector.
      METHODS: The MM cases were collected from the Mesothelioma Registry of Brescia.
      Work histories were obtained via a standardized questionnaire. Investigations
      were conducted in textile machinery manufacturing plants in order to collect
      information regarding the possible use of asbestos parts; at the same time, the
      use of asbestos friction materials and the use of sprayed asbestos for noise
      abatement purposes or thermal insulation was checked in the cotton industry by
      interviewing the management of two companies where a cluster of MM was observed.
      RESULTS: The Mesothelioma Registry of Brescia retrieved and collected 15 MM cases
      with past work in the cotton spinning industry, 4 of them employed in the same
      company. Further search of asbestos use gave positive results as the use of
      friction materials has been widespread since the fifties, while sprayed asbestos
      was not found anywhere in the cotton industry. On the other hand, half of the
      cases were employed during the thirties and forties, when friction materials
      appear to have been asbestos-free. Therefore the other hypothesis of exposure
      could be direct manufacture of asbestos yarn. CONCLUSION: The results of this
      investigation indicate the attribution, at least, of possible asbestos
      exposure"for those cases employed in textile industries since the fifties,
      according to the Re.Na.M guidelines; for those cases employed before that period
      the same classification can be attributed on an epidemiological basis. Previous
      work periods need further investigation in order to demonstrate the circumstances
      of the occupational asbestos exposure, given the heterogeneity of work processes
      and machinery characteristic of this industrial sector.

PMID- 17009672
TI  - [Professional liability of the competent physician: a recent decision of criminal
      cassation].

PMID- 17009673
TI  - [The role of the occupational physician in the prevention of the spreading of
      H5N1 virus avian influenza in exposed workers].
AB  - BACKGROUND: Avian influenza caused by H5N1 virus can be transmitted to exposed
      workers from contact with infected poultry, and is thus, like other zoonoses, the
      responsibility of occupational physicians (OP). The high pathogenicity of H5N1
      virus has caused a 30-75% mortality among infected humans. Most of those subjects
      were occupationally exposed in different areas of poultry raising in Asian
      countries. At the moment, person-to-person transmission, even though possible, is
      unable to start a new human influenza pandemic due to the current genetic
      characteristics of H5N1 virus. However, its spontaneous tendency to mutate must
      alert the international community to the need of eradicating avian influenza in
      poultry as well as preventing transmission to humans. OBJECTIVE: In Italy
      competent OPs are required to take part in prevention of H5N1 avian influenza
      infection of potentially exposed workers, such as poultry sector workers, workers
      engaged in poultry culling, litter management, carcass disposal, zoo and nature
      reserve workers, gamekeepers, veterinarians, biologists, laboratory technicians,
      and health workers caring for possible instances of human infection. METHODS:
      According to Italian legislations, OPs must offer the national community their
      long-standing experience in the fields of workplace environmental monitoring,
      health surveillance, choice of personal protection equipment (PPE) and training
      and information of workers potentially exposed to H5N1 virus about occupational
      risks and correct use of PPE. They must also cooperate with other involved
      professionals to programme antiviral and vaccine prophylaxis. RESULTS AND
      CONCLUSIONS: Occupational physicians can have an important role in contributing
      to the prevention of and scientific research on H5N1 avian influenza virus.

PMID- 17009674
TI  - [The antimony conflict].
AB  - Antimony, which was already well known to the ancients, in the Middle Ages was
      known as Lupus metallorurn--the grey wolf--a key material in alchemists' attempts
      at purifying gold. Over subsequent centuries antimony returned within the bounds
      of conventional scientific and experimental knowledge, but inspired numerous
      studies, works of literature and investigations in important fields of medicine.
      Antimony has always aroused more interest than one might expect from a simple
      metal. The fact that it has been used since ancient times in cosmetics and then
      in alchemy gave it both positive and negative connotations, reflecting its
      possible uses and the benefits for health but also the potential harm. For a
      certain period antimony was virtually the symbol for a range of uses in alchemy
      or empirical medicine, in the face of modern scientific knowledge, and aroused
      debate that went well beyond its actual physical and chemical properties.
      Bernardino Ramazzini's work in the 17th-18th centuries signalled the recognition
      that the use of antimony was linked to health risks. Today it is put to many uses
      in many fields of industry and medicine, so our interest in this metal is no
      longer exclusively a question of history, but is highly topical.

PMID- 17009675
TI  - [Organizational constriction disorders in the military setting: significance of
      training/information].

PMID- 17009676
TI  - [Contractual framing of the competent physician].

PMID- 17009678
TI  - [International convention on Asbestos Monitoring and Analytical Methods --AMAM
      2005-- Venice, December 5-7, 2005].

PMID- 17009677
TI  - [Malignant mesothelioma in the maritime professions].

PMID- 17009679
TI  - [The occupational physician facing the new duties regarding noise and vibration -
      Milan, April 20, 2006. University of Studies --Aula Magna-- Via Festa del
      Perdono, 7].

PMID- 17009680
TI  - Point of view of Italian regions.
AB  - The tragic chain of mortal events, that have happened to workers and people who
      have been exposed to asbestos, proposes clearly an accentuation of the efforts
      that have been undertaken up to now, even in absence of precise national
      directives, in order to give an answer to worries and, sometimes, to real
      consequences of citizens' and workers' asbestos exposure. Region of Tuscany,
      following the initiatives which have been carried out in national and regional
      field for the formerly asbestos-exposed or other carcinogenic agents workers,
      performed a guideline that was just titled "Guidelines on sanitary surveillance
      of formerly exposed to occupational carcinogens workers". The debate, which had
      risen around the sanitary surveillance of the formerly-exposed to occupational
      carcinogenic agents workers, had induced indeed many institutions to take
      decisions on issues which were not yet explicitly regulated by the national law.
      For example the guidelines provided suggestions regarding what bodies--either
      public or private--should be appointed to this task, or the kind of protocols
      should be adopted with all the related collective and individual consequences.

PMID- 17009681
TI  - Point of view of Occupational Health Prevention Units.
AB  - The regulations pertaining to the obligation of continuation of health
      surveillance of workers formerly exposed to asbestos are also examined from the
      point of view of clinical epidemiological usefulness. The outcomes of some types
      of campaigns of health surveillance of formerly exposed workers organized by the
      SSN (National Health Service) are also examined.

PMID- 17009682
TI  - Diagnosis of asbestos-related pleuropolmonary diseases.
AB  - A revision of criteria for diagnosis of asbestos-related pathological conditions
      was performed studying specially asbestosis, pleural plaques and malignant
      mesothelioma, also taking into account the problems connected with
      histopathology. As regards the histological diagnosis of asbestosis, it requires
      the presence of diffuse interstitialfibrosis in a well inflated tissue remote
      from the site of a tumour or other large lesion, plus the presence of two or more
      asbestos bodies in a 1 cm2 section. As regards the imaging diagnosis, the HRTC 4
      point scale proposed by Paris et al. (2004) has been adopted:--0 images not
      suggestive of interstitial pneumonia;--1 modest unilateral or bilateral
      interstitial abnormalities, involving restricted areas if bilateral;--2
      interstitial abnormalities of limited extent, but consistent with a diagnosis of
      asbestosis, i.e. honeycombing, even without other parenchymal changes and even
      though unilateral, or else any two abnormal findings among thickened interlobular
      septa, intralobular lines or subpleural curved lines;--3 numerous bilateral
      changes on several slices involving more than 2/3 of the posterior third of each
      hemi thorax. Only points 2 and 3 were considered consistent with the diagnosis of
      lung fibrosis. Such HRCT findings are not specific for asbestosis, changes in the
      pleural wall such as diffuse plaques and thickenings contribute to the diagnosis
      of asbestosis. As regards the pleural plaques and asbestos bodies we remark that
      they are merely exposition markers. We also discussed the problems the
      pathologist may encounter in diagnosing mesothelioma; in this field the prospects
      are encouraging as microarray analysis are beginning to identify new molecular
      markers for mesothelioma.

PMID- 17009683
TI  - Medical surveillance of workers previously exposed to asbestos.
AB  - According to current Italian law health surveillance of workers exposed to
      asbestos in the past must be maintained even after cessation of asbestos exposure
      (D.Lgs. 277/91). The law, however, makes no reference to timescales or time
      limits for clinical monitoring, nor to who is responsible. The main aims of
      health surveillance of individuals formerly exposed to asbestos can be summarized
      as follows: early diagnosis of the principal diseases associated with asbestos;
      counselling for workers; work-related disease certification; epidemiological
      studies. Medical check-ups entail a complete personal and work history, Chest X
      Ray, respiratory function tests, TLCO. In all cases the worker must undergo a
      LDCT. We propose two new possible biological markers for the health surveillance
      of past-exposed patients: serum mesothelin and osteopontin.

PMID- 17009684
TI  - National epidemiologic surveillance systems of asbestos-related disease and the
      exposed workers register.
AB  - INTRODUCTION: Italy was the main European producer of asbestos for most of the
      20th century and raw asbestos imports wee also significant until the 1990's;
      there was a mean delay of about ten years in the pattern of asbestos consumption
      in Italy compared with the USA, Australia, UK and Scandinavian countries.
      METHODS: A national surveillance system (ReNaM) was implemented to identify cases
      of mesothelioma and investigate the modalities of asbestos exposure. A register
      of exposed workers and a database of companies presumably involved in the
      asbestos exposure problem was also developed. ReNaM has a regional structure and
      an operative centres (COR) have been established in 16 Italian regions. RESULTS:
      The ReNaM database currently contains more than 5,000 mesothelioma cases and for
      3,500 of these exposure modalities have been defined. Cases of pleural
      mesothelioma represent 93% of the total but there were also 334 cases of
      peritoneal mesothelioma, 15 of the pericardium and 14 of the tunica vaginalis of
      the testicle. Cases with ascertained exposure are thus distributed: 67.4%
      occupational exposure (ascertained, probable, possible), 4.3% domestic, 4.2%
      environmental and 1.3% hobby-related exposure, totalling 77.2%; 22.8% had
      unlikely or unknown exposure. The latency period is very long: on average 43.6
      years. The register of asbestos-exposed workers contains figures on exposed
      workers notified to ISPESL up to 2004 and refers to the exposure period 1993
      2003. The data registered cover 160 firms and about 700 workers. CONCLUSIONS: A
      national, coordinated and uniform epidemiological surveillance system of cases of
      mesothelioma and the definition of asbestos exposure through active research is
      extremely important in identifying unexpected contaminating sources. The register
      of asbestos-exposed workers allows risk to be monitored and protection measures
      to be implemented.

PMID- 17009685
TI  - Evaluation of fitness for work: the most challenging situations.
AB  - Evaluation of fitness for work (FW) is the final task of both health surveillance
      and risk evaluation. It's aim is to protect the physical and psychological health
      of workers and respect their professional skills. The Occupational Physician
      faces several difficulties in the evaluation of FW. Moreover, Italian legislation
      on this topic can be variously interpreted and this can cause conflicting
      evaluations. In this session, the most challenging situations in FW evaluation
      will be taken into consideration.

PMID- 17009686
TI  - Fitness for work: the SIMLII Health Surveillance Guidelines.
AB  - Italian legislation on prevention in occupational hygiene and safety, which is
      based largely on European Union Directives, requires health surveillance when
      risk assessment has identified a risk for workers' health. Health surveillance
      must be carried out by the occupational physician and concludes with the issue of
      a fitness for work certificate for the specific job. The guidelines produced by
      the "Italian Society of Occupational Medicine and Industrial Hygiene" (SIMLII),
      through the "Consortium for Accreditation and Updating in Occupational Medicine"
      founded by the "S. Maugeri Foundation of Pavia", Italy, focus firstly on the
      definition of judgment of fitness for a specific job. They outline the
      theoretical basis of the medico-legal terminology for fitness for work, which is
      founded on the concepts of suitability, fitness, capacity, ability, representing
      successive degrees of qualification and specific potential that the worker may
      attain during accomplishment of the tasks involved in the job. To assess fitness
      for a specific job, the occupational physician must consider whether the worker
      possesses the psycho-physical requisites normally needed to do the job, not the
      top levels of such requisites. The intrinsic characteristics of any judgment of
      fitness for work, namely its individual, probabilistic and time-dependent nature,
      are illustrated. The operative methodological model for making a judgment must
      include: assessment of the job and work environment, assessment of the worker
      through health surveillance, comparison and correlation of the two terms of the
      equation: human subject-work environment, the judgment thus made and the choice
      of any necessary measures and/or intervention. The methods for conducting the
      assessment process culminating in a judgement are presented, as stipulated in the
      pertinent legislation, and include the following conclusions: fitness, partial or
      total unfitness, temporary unfitness, fitness provided suitable prescriptions are
      observed,fitness provided some conditions are met. These definitions are analyzed
      in greater depth, especially the possible confusion between partial unfitness and
      fitness provided suitable prescriptions are observed. The employer or worker may
      lodge an appeal with the local health service inspection service against certain
      judgments of unfitness for work. Finally, as health surveillance is governed by
      different legal norms, the contents of which appear to be to some extent
      contradictory, even though aimed at safeguarding the dignity and freedom of the
      worker, the reasons why the occupational physician should take into account
      diseases apart from those of the organs exposed to specific risk are discussed.
      These should be borne in mind when issuing the specific fitness for work
      certificate at the end of preventive and periodical medical examinations.

PMID- 17009687
TI  - Disability and work: fitness for work judgement.
AB  - BACKGROUND: The role of physicians, in particular those dealing with health
      promotion in the workplace, takes on a specific meaning in relation to the
      difficulties that disabled people encounter both in order to reach the workplace
      and to reconcile their working activity with the difficulties that result from
      their condition. Observing the data concerning employment of disabled persons in
      Italy, it becomes dramatically evident that among the disabled subjects of
      working age only 17% are employed. OBJECTIVE: The objective of the occupational
      health physician is to recognise the impairment, study the disability and,
      possibly, eliminate or reduce the handicap. Achieving this target is difficult,
      and there is often a lack in understanding the discomforts experienced by
      disabled people in their working activity. Expression of a judgement of work
      fitness for a specific task is a particularly delicate matter, all the more so if
      the worker is a disabled person. A judgement of work fitness of a disabled person
      should include evaluation of the person's ability and an analysis of the working
      task and the workplace. CONCLUSIONS: Based on our experience, one can safely say
      that working inclusion and integration in work is possible, without any decrease
      in productivity, if an appropriate position is found for disabled workers. The
      occupational health physician has a primary role in the entire process of
      inclusion of disabled people at work, since he/she knows the company, the tasks,
      and the associated risks, and furthermore is able to assess the capabilities and
      abilities of the worker and can thus identify the most suitable and safe working
      situation.

PMID- 17009688
TI  - Protection of third parties in current legislation and preventive practice.
AB  - The problem of safety and the management of risks to third parties, which may be
      caused by a change in the mental or physical health of an employee, is one which
      affects a number of different areas (infectious diseases, psychiatric illnesses,
      conditions of drug and alcohol abuse, etc.). Italian legislation deals with the
      issue of fitness for work through a variety of laws, decrees and regulations
      which, because many of them were issued in different historical circumstances,
      are not always mutually harmonized. The growing complexity of the workplace makes
      the role of the Occupational Physician more complex, and to this person the law
      assigns the exclusive task of monitoring the health of employees in the cases
      covered by the current regulations. In our opinion, the Occupational Physician,
      to the best of his knowledge and conscience, having taken into consideration all
      the aforementioned factors, must take each case on its merits, in the most
      responsible manner possible, weighing up the complexity and delicacy of the
      aspects discussed earlier, and decide to deliver a verdict of fitness and/or to
      break or not to break the obligation of confidentiality, tending, in our view, to
      favour the need to safeguard collective health, or that of third parties, should
      there be a conflict of interest.

PMID- 17009689
TI  - Fitness for work in difficult cases: an occupational medicine experience in a
      University Hospital.
AB  - BACKGROUND: Fitness for work (FW) in certain clinical cases poses significant
      professional challenges for Occupational Physicians (OPs). OBJECTIVES: to discuss
      the role of a public Institute of Occupational Medicine (IOM) in FW, thorough
      description of clinical cases. METHODS: the IOM at the University of Brescia is a
      public clinic available to general practitioners, OPs, other specialists,
      insurance companies, health authorities, employers, trade unions. IOM expert
      opinion on FW may be requested by OPs, employers or workers. In each case,
      occupational and clinical histories are taken, physical examinations, laboratory
      and instrumental tests might be performed, and technical and clinical
      documentation is acquired; expert opinions from other specialists might also be
      sought. Risk assessment (RA) stems from worksite inspections and information from
      company health and safety representatives, or health authorities. RESULTS: a few
      peculiar clinical cases are reported: tremors in a dental hygienist trainee,
      chorioretinitis in a welder, spasmofilia in a nursing aide, obstructive sleep
      apnoea in a steel worker, epilepsy in a metal engineering worker, as well as a
      number of cases fom the same workplace. CONCLUSIONS: FW judgement made by a IOM
      had several advantages from clinical and RA aspects. Work restrictions may not
      always be evidence based and it might be difficult to balance rights and duties
      of patients, employers and OPs; the IOM's wider experience, case discussion with
      the relevant parties, scientific and technical documentation of diagnostic and FW
      processes, strengthen the role of the IOM in dealing with difficult cases and as
      a guarantee from technical and ethical viewpoints.

PMID- 17009690
TI  - Occupational (and non-occupational) risk factors for musculoskeletal disorders.
AB  - BACKGROUND: Musculoskeletal disorders are an important cause of disability and
      absence from work in industrialized countries. A number of studies reported the
      importance of occupational, personal and psycho-social factors in the aetiology
      of these work-related disorders. OBJECTIVES AND METHODS: To stress the complex
      relationships existing between risk factors, reporting findings from reviews and
      original studies regarding two of the most significant musculoskeletal disorders:
      carpal tunnel syndrome (CTS) and low back pain (LBP). CONCLUSIONS: More detailed
      epidemiological studies are needed to explore the interactions between risk (and
      protective) factors, since these can play the role of determinants, confounders
      or effect modifiers.

PMID- 17009691
TI  - Health risks from occupational exposures to mechanical vibration.
AB  - Health effects of occupational exposure to hand-transmitted vibration (HTV) and
      whole-body vibration (WBV) are reviewed. Excessive exposure to HTV from powered
      processes or tools is associated with an increased occurrence of symptoms and
      signs of disorders in the vascular, neurological and musculoskeletal systems of
      the upper limbs. This complex set of disorders is called hand-arm vibration
      syndrome. Long-term occupational exposure to intense WBV is associated with an
      increased risk for disorders of the lumbar spine and the connected nervous
      system. With a lower probability, the neck-shoulder, the gastrointestinal system,
      the female reproductive organs, the peripheral veins, and the cochleo-vestibular
      system are also assumed to be affected by WBV. However, there is weak
      epidemiological support for WBV-induced disorders of organ systems other than the
      lower back. In addition to the health effects of human vibration, this review
      provides information on methods for the protection and health surveillance of
      vibration-exposed workers according to the European Directive 2002/44/EC on
      mechanical vibration.

PMID- 17009692
TI  - Clinical and diagnostic features of upper extremity work-related musculoskeletal
      disorders.
AB  - Upper extremity work-related musculoskeletal disorders, (UE-WMSDs) are one of the
      major causes of work-related disability in industrialized countries. Diagnostic
      criteria for many UE-WMSDs are still under debate, and several different national
      and international studies have attempted to reach a consensus agreement on the
      minimum criteria for case definition of UE-WMSDs. This paper describes clinical
      and diagnostic features of UE-WMSDs, focussing on carpal tunnel syndrome and
      rotary cuff tendinopathy.

PMID- 17009693
TI  - Work-related musculoskeletal disorders with reference to the revised occupational
      diseases list.
AB  - Due to the different compensation schemes, compensated musculoskeletal disorders
      vary widely between countries. In Italy, following the Constitutional Court
      Decision no.179/1988, these disorders were treated as "non-listed" diseases and
      workers must prove their occupational origin by submitting a compensation claim
      for musculoskeletal disorders to INAIL. The Italian Workers Compensation Agency
      (INAIL) supplied guidelines for the management of these claims. Recently, a new
      occupational diseases list has been submitted to the Labour Ministry for
      approval. This list includes musculoskeletal disorders of the upper limb, back
      and knee.

PMID- 17009694
TI  - Bioethics, technology and human dignity: the Roman Catholic viewpoint.
AB  - Many important questions dealing with human dignity in medical research are
      raised by new medical technologies. The paper presents the Roman Catholic
      approach to the use of new technologies, the research on human embryos, the
      ethical aspects of studies on human genome. The concept of "human ecology", as
      proposed by John Paul II, is to reconcile human dignity, the academic freedom of
      research, the sacredness of life understood as its quality so important for the
      cultural growth of Homo sapiens. To protect human ecology it is our moral duty to
      defend human dignity and to recognize the importance of those values that are
      fundamental in the process of development of human species.

PMID- 17009695
TI  - Robotics and artificial intelligence: Jewish ethical perspectives.
AB  - In 16th Century Prague, Rabbi Loew created a Golem, a humanoid made of clay, to
      protect his community. When the Golem became too dangerous to his surroundings,
      he was dismantled. This Jewish theme illustrates some of the guiding principles
      in its approach to the moral dilemmas inherent in future technologies, such as
      artificial intelligence and robotics. Man is viewed as having received the power
      to improve upon creation and develop technologies to achieve them, with the
      proviso that appropriate safeguards are taken. Ethically, not-harming is viewed
      as taking precedence over promoting good. Jewish ethical thinking approaches
      these novel technological possibilities with a cautious optimism that mankind
      will derive their benefits without coming to harm.

PMID- 17009696
TI  - Ethics in the use of new medical technologies for neurosurgery: "Islamic
      viewpoint".
AB  - It is very clear from developments in technology and its global expansion that we
      cannot survive the 21st century with 20th century ethics. The developments in
      technology, especially those in the field of medicine have a direct and fast
      effect on human life expectation and survival. Thus, this issue has to be seen
      and studied in the context of ethics. In this paper, ethical principles in the
      application of new medical technologies in neurosurgery from an Islamic viewpoint
      will be given.

PMID- 17009697
TI  - Shadow of Buddhism and Shintoism in neurosurgical practice in Japan.
AB  - BACKGROUND: In Japan, almost all culture and civilization were introduced from
      abroad; in the past from China and now from U.S. and European countries, owing to
      her geographical features circumscribed by oceans and separated from the
      continents. Neurosurgical science and practice have been received in the same way
      as other activities. However, there are some exceptions such as organ
      transplantation from the brain dead and brain-dock, which means a brain check-up
      system of asymptomatic brain diseases. Reasons why these are practised or not in
      Japan are considered from the viewpoint of Buddhism and Shintoism. If our special
      practises could appeal to people in other countries, our neurosurgical philosophy
      might become widespread and welcome worldwide. FINDINGS: Organ transplantations
      from brain dead have routinely been performed in many countries, while only 37
      cases have been executed in Japan, after the Japanese government accepted its
      application in 1997. In contrast, brain-dock is widely practised without any
      national insurance systems, while this is rarely practised in other countries. It
      seems to me that Buddhism and Shintoism have influenced on these special
      situations, due to extreme fear and impurity of the dead body and a way of
      comprehending the oneness of body and mind, and also deep concern for the impact
      of their diseases to their families rather than for themselves. SUMMARY: We
      neurosurgeons should realize that our profession is directly related to ultimate
      human sufferings such as aging, disease, and death, as pointed out by Gautama
      Buddha. We are in fact in a position to study the real way for resolution of the
      human sufferings, mentally and physically. Based on our experiences, the
      foundation of a new academic discipline like "cultural medical science" should
      urgently be considered in all parts of the world and in light of individual
      cultural, economical, geographical, and population problems.

PMID- 17009698
TI  - Current status of medical technology.
AB  - BACKGROUND: Medical Technology (MT) provides innovative instrumentation and
      methods designed for the purpose of improving prevention, diagnostics, therapy
      and rehabilitation. MT rooting in science, engineering and the biosciences is
      characterized by its inter- and transdisciplinarity. METHOD: The current status
      of MT is described emphasizing the five aspects: (1) review of milestones, (2)
      the impact of MT on the health care system, (3) the economic significance of MT,
      (4) the financial resources dedicated to research and development in MT, and (5)
      the challenges for education and training in MT. The material used is a
      government issued survey on the situation of MT in Germany, data of health care
      authorities and congress reports from World Conference on Medical Physics and
      Biomedical Engineering 2005. RESULTS: The following fields of MT have emerged in
      recent years and will dominate future development: BioMEMOS, imaging technology,
      minimally invasive surgery, computer assisted diagnosis, therapy and treatment
      monitoring, e-health/telemedicine/ networking, and medical engineering for
      regenerative medicine. Development of MT is driven by the following facts, (1)
      early and individualized diagnosis enables better treatment, (2) MT enhances cost
      effectiveness in health care, (3) MT is an economic factor based on fast
      innovation cycles, a roughly 50% export share and a 6% growth rate in turnover
      during the last 10 years. A downward tendency of the domestic MT market is a
      challenge for appropriate measures in improving both the economic and the
      academic infrastructure, in particular by targeted actions to support research
      and education. CONCLUSION: The impact of MT on prevention, diagnostics, therapy
      and rehabilitation is significant and still increasing. Due to a wide spreading
      in all medical areas, the high innovation rate, and the potential to improve
      health care, MT is considered one of the key technologies even in the future.

PMID- 17009699
TI  - Uncertainty in diffusion tensor based fibre tracking.
AB  - BACKGROUND: Diffusion tensor imaging and related fibre tracking techniques have
      the potential to identify major white matter tracts afflicted by an individual
      pathology or tracts at risk for a given surgical approach. However, the
      reliability of these techniques is known to be limited by image distortions,
      image noise, low spatial resolution, and the problem of identifying crossing
      fibres. This paper intends to bridge the gap between the requirements of
      neurosurgical applications and basic research on fibre tracking uncertainty.
      METHOD: We acquired echo planar diffusion tensor data from both 1.5 T and 3.0 T
      scanners. For fibre tracking, an extended deflection-based algorithm is employed
      with enhanced robustness to impaired fibre integrity such as caused by diffuse or
      infiltrating pathological processes. Moreover, we present a method to assess and
      visualize the uncertainty of fibre reconstructions based on variational complex
      Gaussian noise, which provides an alternative to the bootstrap method. We compare
      fibre tracking results with and without variational noise as well as with
      artificially decreased image resolution and signal-to-noise. FINDINGS: Using our
      fibre tracking technique, we found a high robustness to decreased image
      resolution and signal-to-noise. Still, the effects of image quality on the
      tracking result will depend on the employed fibre tracking algorithm and must be
      handled with care, especially when being used for neurosurgical planning or
      resection guidance. An advantage of the variational noise approach over the
      bootstrap technique is that it is applicable to any given set of diffusion tensor
      images. CONCLUSIONS: We conclude that the presented approach allows for
      investigating the uncertainty of diffusion tensor imaging based fibre tracking
      and might offer a perspective to overcome the problem of size underestimation
      observed by existing techniques.

PMID- 17009700
TI  - Robotics in neurosurgery: which tools for what?
AB  - Robots are the tools for taking advantage of the skills of computers in achieving
      complicated tasks. This has been made possible owing to the "numerical image
      explosion" which allowed us to easily obtain spatial coordinates, three
      dimensional reconstruction, multimodality imaging including digital subtraction
      angiography (DSA), computed tomography (CT), magnetic resonance imaging (MRI) and
      magneto encephalography (MEG), with high resolution in space, time, and tissue
      density. Neurosurgical robots currently available at the operating level are
      being described. Future evolutions, indications and ethical aspects are examined.

PMID- 17009701
TI  - Computer- and robot-aided head surgery.
AB  - In this paper new methods and devices for computer and robot based head surgery
      are presented. A computer based planning system for CMF-surgery allows the
      surgeon to plan complex trajectories on the head of the patient for operations
      where bone segments were cut out and shifted. Different registration methods have
      been developed and tested. A surgical robot system for bone cutting on the head
      has been developed and evaluated at the patient in the operating theatre. In
      future, laser cutting of bones with a robot will be seen as a new powerful method
      for robot based surgery. A 3D augmented reality system will assist the surgeon in
      the future by augmenting virtual anatomical structure into the situs.

PMID- 17009702
TI  - Telecontrolled micromanipulator system (NeuRobot) for minimally invasive
      neurosurgery.
AB  - BACKGROUND: To perform less invasive neurosurgery, a telecontrolled
      micromanipulator system has been developed and applied to clinical situations.
      Basic experiments for telesurgery have also been conducted. METHOD: A cadaver
      head was used to carry out surgical simulation of the opening of the sylvian
      fissure and third ventriculostomy. After obtaining permission from the Ethical
      Committee of Shinshu University School of Medicine, part of the recurrent
      meningioma in a 45-year-old man was removed. As basic experiment for telesurgery,
      surgical simulation was also conducted in a rat brain with the operating console
      transported to a hospital 40 km distant from the University. FINDINGS: Opening of
      the sylvian fissure and third ventriculostomy were accurately performed. Tumour
      removal in a patient with recurrent meningioma was safely achieved. Surgical
      simulation in the rat brain was accurately and correctly carried out, operated on
      from a hospital 40 km distant. CONCLUSIONS: The NeuRobot, telecontrolled
      micromanipulator system, can be used as a tool for less invasive neurosurgery.

PMID- 17009703
TI  - Usefulness of intraoperative magnetic resonance imaging for glioma surgery.
AB  - BACKGROUND: Radical resection of gliomas can increase patient's survival. There
      is known concern, however, that aggressive tumour removal can result in
      neurological morbidity. The objective of the present study was to evaluate the
      usefulness of low magnetic field strength (0.3 Tesla) open intraoperative
      magnetic resonance imaging (iMRI) for complete resection of glioma with emphasis
      on functional outcome. METHODS: From 2000 to 2004, 96 patients with intracranial
      gliomas underwent tumour resection with the use of iMRI in Tokyo Women's Medical
      University. There were 50 men and 46 women; mean age was 39 years. Tumour volume
      varied from 1.2 ml to 198 ml (median: 36.5 mL). Resection rate and postoperative
      neurological status were compared between control group (46 cases, operated on
      during the initial period after installation of iMRI), and study group (50 most
      recent cases, in whom surgery was done using established treatment algorithm and
      improved image quality). FINDINGS: Overall, mean resection rate was 93%, and
      medial residual tumour volume was 0.17 ml. Total tumour removal was achieved in
      44 cases (46%). Compared to control group, resection rate in the study group was
      significantly higher (91%, vs. 95%; P < 0.05), whereas residual tumour volume was
      significantly smaller (1.7 mL vs. 0.025 mL; P < 0.001). Nine patients in the
      control group (20%) and 24 in the study group (48%) experienced temporary
      postoperative neurological deterioration (P < 0.01), however, the rate of
      permanent morbidity evaluated 3 months after surgery did not differ significantly
      between the groups investigated (13% vs. 14%). CONCLUSIONS: Use of iMRI during
      surgery for intracranial gliomas permits to attain aggressive tumour resection
      with good functional outcome. Nevertheless, surgical experience with the iMRI
      system, establishment of treatment algorithm, and improvement of image quality
      are of paramount importance for optimal results.

PMID- 17009704
TI  - Intraoperative magnetic resonance imaging in neurosurgery: the Brigham concept.
AB  - The resection of brain tumors is limited by the surgeon's ability to precisely
      define margins. To overcome this problem, various neuronavigational tools have
      been used. The development of image-guided navigation systems represents a
      substantial improvement in the microsurgical treatment of various intracranial
      lesions. However, a major drawback of this technology is that they use images
      acquired preoperatively, on which the surgical planning and intraoperative
      performance is based. As the intracranial anatomy dynamically changes during a
      neurosurgical procedure, only intraoperatively acquired images can provide the
      neurosurgeon with the information needed to perform real-time, image-guided
      surgery. Because magnetic resonance imaging best delineates the soft-tissue
      extent of most tumors, it currently remains the superior method for
      intraoperative image guidance. In this review, we outline the development as well
      as current and possible future applications of the intraoperative MRI (iMRI) unit
      at the Brigham and Women's Hospital, Boston, MA.

PMID- 17009705
TI  - Intraoperative high-field MRI: anatomical and functional imaging.
AB  - Intraoperative high-field magnetic resonance (MR) imaging with integrated
      microscope-based navigation is at present one of the most sophisticated technical
      methods providing a reliable immediate intraoperative quality control. It enables
      intraoperative imaging at high quality that is up to the standard of up to date
      pre- and postoperative neuroradiological routine diagnostics. The major
      indications are pituitary tumor surgery and glioma surgery. In pituitary tumor
      surgery intraoperative MRI helps to localize hidden tumor remnants that would be
      otherwise overlooked. The same is true for glioma surgery, where the optimal
      extent of resection by simultaneous preservation of functional integrity can be
      achieved. This is possible since high-field MR imaging offers various modalities
      beyond standard anatomical imaging, such as MR spectroscopy, diffusion tensor
      imaging, and functional MR imaging which may also be applied intraoperatively,
      providing not only data on the extent of resection and localization of tumor
      remnants but also on metabolic changes, tumor invasion, and localization of
      functional eloquent cortical and deep-seated brain areas.

PMID- 17009706
TI  - Intraoperative MR imaging: preliminary results with 3 tesla MR system.
AB  - Aim of this study is to present the initial clinical experience with 3 tesla
      intraoperative MR (ioMR). MATERIAL AND METHODS: The 3T MRI suite is built
      adjacent to the neurosurgical operation theatre. The magnet room and the
      operation theatre are interconnected by a door and both RF-shielded. Before the
      operation, the magnet (3T Trio, Siemens) and the console rooms are disinfected.
      Whenever imaging is needed during the operation, the door is opened and the
      patient is transferred from the operation table to the magnet cradle. Axial,
      sagittal and/or coronal TSE T2, SE T1 and 3D Flash T1 weighted images (4-6 mm
      section thickness, 1 mm interslice gap) are obtained according to the lesion.
      Total examination time is approximately 10 minutes. RESULTS: Twenty-six patients
      were examined with ioMR. There were ten female and seven male patients. Lesions
      were pituitary adenoma in 10, low grade glial tumor in 9, meningioma and high
      grade glial tumor in 2 each and metastasis, haemangioblastoma and chordoma in one
      each. Follow-up time was 1 to 9 months. In 16 patients the first intraoperative
      examination revealed gross total tumor excision. However, in 10 patients due to
      tumor remnants surgical intervention was continued and a second examination
      revealed gross total tumor excision in all. Postoperative routine MR examinations
      confirmed total tumor excision in all patients. No complication occurred in this
      series. CONCLUSION: This small group of patients examined with ioMR demonstrated
      that the procedure is simple, helpful in achieving gross total tumor excision
      without complications.

PMID- 17009707
TI  - [Veterinary parasitology, where to?].

PMID- 17009708
TI  - [Reaction of bovine endothelial cells in vitro to coccidia (Eimeria bovis,
      Toxoplasma gondii, Neospora caninum) infections as the expression of a non
      adaptive immune response].
AB  - Eimeria (E.) bovis sporozoites as well as Toxoplasma (T.) gondii and Neospora
      (N.) caninum tachyzoites can invade bovine endothelial cells (BUVEC) in vitro and
      develop to next stage meronts within 15-20 and 3-4 days, respectively. The latter
      differences suggest different immune evasion strategies, particularly concerning
      innate reactions. Realtime RT-PCR techniques were used to determine transcript
      levels of genes relevant in this sense, i.e. adhesion molecule, chemokine, growth
      factor GM-CSF, cyclooxygenase 2 (COX-2) and iNOS genes in infected cells. In
      addition, adhesion of neutrophils (PMN) to infected BUVEC monolayers was
      quantified. Effects differed between E. bovis and T. gondii/N. caninum as the
      latter two species strongly enhance the transcription of all genes in question
      and induce PMN adhesion to infected BUVEC whereas E. bovis either caused only
      weak responses or failed to enhance gene transcription as in case of CXC
      chemokines and COX-2. It even down regulates adhesion molecule expression in
      response to cytokines. The differences between the species may reflect differing
      immune evasion strategies, in case of E. bovis favouring its long lasting
      development to macromeronts.

PMID- 17009709
TI  - [Comparison of different methods for examining the feces of suckling piglets for
      Isospora suis].
AB  - A highly sensitive diagnostic method is of great importance for detection of I.
      suis (Isospora suis). In the present study KSFV (combined sedimentation-flotation
      method) using different flotation solutions (NaCl, ZnSO4, NaCl-sucrose) was
      investigated regarding sensitivity, costs and expenditure of human labour in
      comparison to FV (flotation method) using NaCl-sucrose solution and to AM
      (autofluorescence microscopy). Ninety faecal samples were examined. Using AM,
      oocysts were detected in 83.3% of the samples. In cases of KSFV and FV,
      respectively, 41.1% to 53.3% of samples were tested positive. The quantity of
      detected oocysts was markedly higher in AM than in KSFV or FV. Therefore AM is
      the most sensitive of the comprised methods. The expenditure of labour is lowest
      in AM, time exposure is lower in FV than in KSFV. For performance of AM a
      fluorescence microscope is required contrary to KSFV and FV.

PMID- 17009711
TI  - Prevalence and significance of gastrointestinal helminths and protozoa in South
      American Camelids in Switzerland.
AB  - A cross sectional study was conducted to determine the prevalence and
      significance of endoparasitic infections in South American Camelids (SAC) in
      Switzerland. Qualitative and quantitative coproscopic examinations were performed
      in 38 farms during the grazing period. Management practices with possible
      interference with parasitic infections were analyzed. On the farm level
      prevalences of endoparasitic infections were: trichostrongyles 87%; Trichuris sp.
      74%; Capillaria sp. 68%; Nematodirus battus 63%; Nematodirus sp. 53%;
      Dicrocoelium dendriticum 34%; Moniezia sp. 8%; Fasciola hepatica 5%;
      protostrongylids 5%; Eimeria macusaniensis 68%. The level of helminth egg
      excretion was generally low. The highest values were recorded for
      trichostrongyles with an average of all investigated farms of 53 eggs per gram of
      faeces. The mean trichostrongyle egg output was approximately three-fold in SAC
      on farms that also kept sheep and/or goats, although this difference was not
      significant (P = 0.11). Clinical trichostrongylidosis was not reported from any
      of the farms. The low infection level with gastrointestinal nematodes is
      attributed to the defaecation behaviour of the SAC depositing their faeces
      focally on small spots on pasture. As a consequence, pasture infectivity is
      largely restricted to the area adjacent to the dung piles. Dicrocoeliosis is
      regarded as the most relevant parasitic infection of llamas and alpacas in
      Switzerland causing severe clinical symptoms and death in untreated animals.
      Sixteen per cent of the owners regularily treated their herds against
      dicrocoeliosis using praziquantel at a dose of 50 mg/kg body weight orally.

PMID- 17009710
TI  - Prevalence and age-dependent occurrence of intestinal protozoan infections in
      suckling piglets.
AB  - A cross-sectional survey was performed on 20 pig breeding farms in southern
      Hesse, central Germany, to evaluate the prevalence and age-dependent occurrence
      of intestinal protozoan parasites in unweaned piglets. Faecal samples of 514
      clinically unaffected piglets of different age (< 1 to 5-7 weeks) were examined
      using the sodium acetate-acetic acid-formalin (SAF) concentration technique.
      Infections with the following protozoan species were detected: Balantidium coli
      (16 of 20 farms), Entamoeba sp. (15), Jodamoeba sp. (14), Isospora (I.) suis (9),
      Chilomastix sp. (6) and Eimeria spp. (6). The protozoan species differed in the
      start and course of (oo)cyst excretion. I. suis oocysts and Jodamoeba cysts were
      detected already in the first week of life whereas shedding of the other
      parasites started later on. The prevalence of Isospora oocyst excretion increased
      to a maximum (18%) in 2-3 weeks old animals followed by a sharp decline. The
      proportion of Balantidium, Entamoeba or Jodamoeba positive suckling piglets
      continously increased until the age of 5-7 weeks to 60%, 52% and 22%,
      respectively, whereas that of Chilomastix positive animals remained on a low
      level of 8-12% independent of the age. Eimeria oocysts were found transiently in
      the faeces of 1-4 weeks old piglets.

PMID- 17009712
TI  - [The helminth and coccidial fauna of pheasants (Phasianus colchicus) in view of
      the specific environmental conditions in pheasantries and in the wild].
AB  - Between October 1999 and January 2000 all together 151 male pheasants were
      examined for endoparasites. 33 one-year-old birds came from two pheasantries, the
      remaining 118 birds, aged between one and five years, were wildlife animals. The
      infestation extensy of all pheasants with endoparasites were 96.7%. A mostly low
      infestation with coccidia of the three species Eimeria (E.) phasiani, E.
      duodenalis and E. tetartooimia were detected in 41% of all birds. E. tetartooimia
      was found in Germany for the first time. In 67.5% of the pheasants the five
      different species of capillaria (Capillaria (C.) annulata, C. bursata, C.
      contorta, C. perforans, C. phasianina) and in 84.1% the nematode Heterakis
      gallinarum were present. Pheasants in the capture group showed higher infestation
      intensy and extensy. In 51.5% of the pheasants of the capture group Syngamus
      trachea was present. In one pheasant an acanthocephalus (Plagiorhynchus
      cylindraceus) was detected for the first time in Germany and in two pheasants a
      trematode of the genus Echinostoma was present.

PMID- 17009713
TI  - Feasibility of genus-specific real-time PCR for the differentiation of larvae
      from gastrointestinal nematodes of naturally infected sheep.
AB  - Results of real-time PCR analysis of coproculture third stage larvae (L3) using
      genus specific TaqMan minor groove binder probes were compared with the results
      of morphological differentiation of L3 after coprocultured and direct
      morphological worm differentiation from gastrointestinal samples of eight sheep
      with naturally acquired nematodes infections. Faecal egg counts prior to
      postmortem confirmed infections with trichostrongyles with a geometric mean count
      of 4828 eggs per gram for all sheep. Individual egg counts correlated positively
      with total worm counts (correlation coefficient 0.794). Five different nematode
      species and one genus were found in the abomasi and small intestines: Cooperia
      curticei, Haemonchus contortus, Nematodirus spp., Teladorsagia (Ostertagia)
      circumcincta, Trichostrongylus axei and Trichostrongylus colubriformis.
      Coproculture of faecal eggs yielded five of these, Cooperia spp., Haemonchus
      spp., Ostertagia/Teladorsagia spp. and Trichostrongylus spp. Comparison between
      morphological L3 and worm differentiation data showed high congruence (94%). The
      agreement between PCR analysis of L3 after coproculture and direct morphological
      worm differentiation was 84%. Thus, real-time PCR was found to be suitable as a
      speedy and reliable diagnostic tool for the assessment of gastrointestinal
      nematode infections of ruminants in the field.

PMID- 17009714
TI  - Occurrence of hydatidosis in slaughter buffaloes (Bos bubalis) and helminths in
      stray dogs in Kathmandu Valley, Nepal.
AB  - The study aimed at identifying the occurrence of hydatidosis in slaughter
      buffaloes and helminth eggs, particularly Taenia spp. eggs in stray dogs' fecal
      samples in Kathmandu Valley, Nepal. The study period was from November, 2004 to
      April, 2005. A total of 500 buffalo carcasses in a slaughterhouse, at the
      riversides and individual butchers'sites were examined for the presence of
      hydatid cysts. The cyst fluid was collected and microscopically examined to
      determine if it was fertile or not. Of the 500 carcasses examined, 10.6% had
      hydatid cysts. Specifically, the slaughterhouse carcasses had a 6.7% occurrence
      of hydatid cysts, whereas those examined at riversides and individual butcher
      places had 10.0% and 12.7%, respectively. Distributions of the hydatid cysts by
      specific organs showed single occurrence of 6.4% in lungs, 2.4% in livers and
      1.8% in both, livers and lungs. In a total of 53 infected buffaloes, 58.5% were
      fertile and 41.5% sterile cysts. Overall, 366 faecal samples from stray dogs were
      collected around buffaloes slaughtering areas (slaughterhouse and individual
      butcher places), riversides, garbage sites and temple sites. These samples were
      examined by formalin-ether concentration technique to investigate the presence of
      different helminth eggs. The total prevalence of Taenia, hookworms,
      Trichuris/Capillaria,Toxocara, Spirometra and Physaloptera eggs were 12.8%,
      18.3%, 19.1%, 12.8%, 1.4% and 1.9%, respectively.

PMID- 17009715
TI  - A study on the seasonal epidemiology of Anoplocephala spp.-infection in horses
      and the appropriate treatment using a praziquantel gel (Droncit 9% oral gel).
AB  - In a study on the seasonal dynamics of the gastro-intestinal nematode egg
      production in horses, one breeding farm also revealed a particularly high
      prevalence of Anoplocephala spp. infection. Consequently, this farm was chosen
      for analysing the seasonal pattern of the tapeworm egg excretion over a one year
      period in order to establish the most favourable periods for an appropriate and
      successful cestocidal treatment. The seasonal analysis showed a significantly
      higher (p < 0.05) Anoplocephala spp. egg excretion between July and October, i.e.
      during the second part of the grazing period. This result clearly underlines the
      importance of a cestocidal treatment during that period of the year.
      Subsequently, horses of this farm and of a second farm with a high prevalence of
      Anoplocephala spp. were used to evaluate the efficacy of praziquantel in a
      specific oral gel formulation for horses under field conditions. The efficacy of
      praziquantel was tested in a total of 33 horses from the two farms harbouring a
      coproscopically detected Anoplocephala spp. infection prior to treatment.
      Praziquantel (Droncit 9%, oral gel, 1 mg/kg bodyweight) was administered to the
      horses according to their body weight. The efficacy of the drug was evaluated ten
      days after treatment by a double faecal analysis. Thereby, no Anoplocephala spp.
      eggs were found in the faeces of 32 horses (97%). The single horse remaining
      positive for Anoplocephala spp. eggs did not completely swallow the anthelmintic
      gel and consequently, did not receive the appropriate dose of the drug.

PMID- 17009716
TI  - [Incidence and control of the American giant liver fluke, Fascioloides magna, in
      a population of wild ungulates in the Danubian wetlands east of Vienna].
AB  - Fascioloides magna,the giant liver fluke, is an introduced parasite imported to
      Europe with infected game which is endemic in the Austrian wetlands of the Danube
      from Vienna to the Slovakian border. Due to its pathogenicity (especially in roe
      deer) and its potential of transmission to domestic ruminants a project on the
      epidemiology and control of this parasite was carried out between 2000 and 2005.
      To assess distribution faecal droppings from red deer were collected in an area
      along the Danube and livers of red and roe deer shot or found dead were examined.
      Simultaneously, triclabendazole-medicated feed was offered repeatedly in several
      areas of known fluke presence from 2001. The average prevalence of infection as
      demonstrated by Fascioloides eggs in droppings (n = 145) was 6.3%, with > 50% in
      some areas. Infection rates decreased from 11.3% (01/2001) to 1.5% (04/2002) in
      the whole area. In Fischamend, a highly endemic area, prevalences in monthly
      samples (n = 25) decreased from 70% (01/2001) to less than 1% (01/2005).
      Similarly, the number of eggs per gram of faeces was significantly reduced. Of
      457 red deer livers 15.8% were positive. In the Fischamend area, a reduction of
      positive livers was also found (2000:100%; 2005:13%), as well as a reduction of
      the numbers of flukes/liver. Control of F. magna in the Danubian wetlands by
      anthelmintic treatment proved to be successful although eradication was not
      achieved.

PMID- 17009717
TI  - [The incidence of Dicrocoelium dendriticum in Emmental].
AB  - A cross-sectional field study on the prevalence of Dicrocoelium dendriticum was
      performed in the Emmental. The study included 211 bovines, 170 equines, 20
      ovines, 46 caprines and 23 rabbits (from 119 farms). In addition, laboratory
      routine diagnostic data obtained from 2.840 animals--all originating from the
      same area of investigation--were assessed in the same way. The infection extent
      concerning the different animal species were the following: bovines 46%, equines
      12%, ovines 30%, caprines 48% and rabbits 9%. Univariate analyses of baseline
      epidemiological data identified no significant risk factors, with the exception
      of the type of stable used. Bovines kept in a modern free ranging stable had a
      significantly lower chance of infection with D. dendriticum than cattle in
      conventional tie stalls. The epidemiological data characterizing the area of
      investigation suggest the following procedure to reduce the problem of
      dicrocoeliosis: Pasturing animals of all ages should be regularly dewormed (e.g.
      every six week during pasture) using a compound effective against D. dendriticum.
      A treatment is especially indicated at the time after pasture in autumn or before
      housing the animals in winter. In spring, only animals having pastured the year
      before need to be treated prior to pasture in the new year. However, it is
      recommended to perform an economic analysis comparing costs of treatment versus
      putative costs of damage prior to the initiation of a strategic campaign: animal
      welfare aspects have to be considered. The laboratory routine diagnostic data
      showed infection extent similar to those of the cross-sectional study: bovines
      60%, equines 24%, ovines 26%, caprines 31%, rabbits 32%. Atypical hosts such as
      dogs and cats exhibited low infection extent (3% and 1%, respectively), rather
      reflecting a gastro-intestinal passage of parasite eggs ingested by consumption
      of infected livers or by coprophagy of ruminant faeces.

PMID- 17009718
TI  - [Dermacentor reticulatus (Fabricius, 1794)--distribution, biology and vector for
      Babesia canis in Germany].
AB  - This work deals with occurrence, distribution as well as biology and vectorial
      capacity of the ornate dog tick (Dermacentor (D.) reticulatus). Until 30 years
      ago this tick has only been described in a few natural foci in southern Germany.
      Its distribution has however expanded in the course of the last years. With the
      exception of northern Germany it is now covering large areas of Germany. This is
      particularly the case in the Upper Rhine Valley, Saarland and the Mark
      Brandenburg. However, it is endemic in many other areas of Germany as well. The
      transformation of agricultural land into fallow land, an increase in host
      reservoirs and climatic changes are discussed as main contributors to this
      change. Little is known about the role of this species as a vector for virus,
      rickettsia, bacteria and protozoa as well as its medical and veterinary
      importance. D. reticulatus is a vector for Babesia canis canis. It is reported
      here about a case of autochthonous babesiosis in a dog from Berlin/Brandenburg.

PMID- 17009719
TI  - [Tick infestation and the prevalence of Borrelia burgdorferi and Babesia
      divergens in cattle in Bavaria].
AB  - During the grazing period 2002 319 cattle from 31 farms located in 6 districts of
      southern Bavaria were examined for the presence of ticks in 4- to 5-week
      intervals, and 287 serum samples were tested for the presence of antibodies
      against Borrelia burgdorferi and Babesia divergens. Ticks were detected in all 31
      farms with a mean prevalence of 69%. 3218 out of 3453 collected ticks were Ixodes
      ricinus; 139 nymphs, 19 larvae and 77 damaged adult specimens could only be
      determined to the Genus level (Ixodes). The seasonal pattern revealed the highest
      frequencies of ticks in May/June and September. The intensity of tick infestation
      of positive animals was generally low. 76.5% of parasitized cattle had 1-6 ticks
      per day of investigation. Individual cattle showed up to 250 ticks per day. The
      percentage of infested animals in each herd varied within the period between 0
      100%. The examination of serum samples by immunofluorescence technique (IFAT)
      revealed positive anti-Borrelia antibody titers (> or = 1:64) for 45.6% of the
      animals. The within-farm seroprevalence of borreliosis ranged from 20 to 100% in
      27 of the 31 farms. A significant correlation could be detected between the
      number of ticks/cattle and the anti-Borrelia burgdorferi IgG-titer. By contrast,
      there was no significant correlation between the age of the animals and anti
      Borrelia serum titers. For comparative reasons, 64 IFAT-positive serum samples
      were tested by Western blot techniques for the presence of antibodies cross
      reacting with Borrelia garinii antigen. These analyses revealed that 69% of the
      samples reacted positively, 28% were unclear and 3% were negative. Examinations
      of the 287 serum samples for the presence of anti-Babesia divergens antibodies
      revealed one positive animal with a titer of 1:16.

PMID- 17009721
TI  - [Sarcoptes scabiei var. suis in a closed pig breeding and fattening herd and
      control possibilities after treatment].
AB  - On an Austrian pig breeding and finishing farm containing 13,000 pigs a mange
      prevalence of 38.7% according to the results of the skin scraping and 28.2% based
      on serology was determined. Due to the insufficient treatment (single treatment
      of the sows using Phoxim [Sebacil pour on]), sustainable control was impossible.
      That could be confirmed by the high number of mange positive gilts and finishing
      pigs. Before eradication started the following prevalences of mange could be
      found: sows 6.74% (skin scrapings), respectively 6.18% (serologically), gilts
      18.18% resp 28.67%, finishing pigs 54.35% and 38.58%. The breeding stock for
      eradication was treated with doramectin (Dectomax) injectable solution and the
      finishing pigs with Ivomec-praemix, both applied twice. The success of treatment
      of the different farm units and of different age groups was controlled for the
      following ten months by combined diagnostic methods. In addition to skin
      scrapings, serum and colostral samples were carried out using a commercially
      available ELISA licensed for investigation of blood serum and colostrum. After
      treatment antibodies in the serum of the sows and gilts and Sarcoptes mites in
      their skin scrapings were detectable for up to four months after treatment. In
      serum samples of piglets and colostrum samples antibodies against Sarcoptes mites
      were detectable up to five months after final treatment. Due to the higher level
      and longer verifiability of antibodies in blood samples of piglets for five
      months after treatment and high prevalences their use as a diagnostic tool can be
      recommended. In contrast the use of colostral samples for routine diagnosis
      should be investigated more thoroughly. The comparison of the results of
      different diagnostic methods showed that for reliable mange diagnosis combined
      methods are recommended.

PMID- 17009720
TI  - [Seroprevalence of Anaplasma phagocytophilum infection in dogs in Germany].
AB  - To determine the prevalence of Anaplasma phagocytophilum in dogs in Germany serum
      samples from 1124 dogs that were under suspicion of having anaplasmosis were
      examined. The samples were tested by an indirect immunofluorescence test (OFT)
      for antibodies to A. phagocytophilum. The geographical origin of positive cases
      were analysed with an geographic information system. Antibodies to A.
      phagocytophilum were found in 563 (50.1%) of the tested dogs. 166 dogs came from
      Saarland, 161 from North Rhine-Westphalia, 134 from Baden-Wuerttemberg, 33 from
      Bavaria, 22 from Rhineland-Palatinate, 11 from Hamburg, 10 from Brandenburg, 9
      from Lower Saxony, 8 from Hesse and Berlin respectively and 1 from Schleswig
      Holstein. Clinical signs and laboratory findings of 26 seropositive dogs were
      analysed. Those dogs showed a low haematocrit, thrombocytopenia and leucocytoses
      as well as higher values for alkaline phosphatase, ALAT und bilirubin. The
      clinical signs were lameness in 13 dogs, lethargy in 5, and uveitis in 3 dogs.
      Rhinitis and lymphadenopathy was found in 2 dogs and retinal detachment with
      blindness in 1 dog.

PMID- 17009722
TI  - [Questionnaire on the incidence and control of fleas in dogs and cats presented
      to German small animal practices].
AB  - 2590 small animal practitioners in Germany have been asked by a questionnaire
      from which 1694 (65.4%) replied. 1186 of these veterinarians (70%) often see
      ectoparasite infestation. Fleas are predominant and occur on cats (1016/60%),
      followed by dogs (424/25%), small mammals and birds (254/15%). Flea infestations
      on dogs and cats are observed throughout the year, but the prevalences are
      generally higher during the summer season. The results reveal that topically
      administered spot-on formulations is the most popular method used for flea
      control. The most common applied antiparasitic substances both in dogs and in
      cats were fipronil (535/31.6%; 690/40.7%), imidacloprid (290/17.1%; 417/24.6%)
      and selamectin (267/15.8%; 319/18.8%). Due to 771 (45.5%) of the answering
      veterinarians the animal owner himself, and according 694 (41%) respectively 229
      (13.5%) of the replies the veterinarian or the veterinary technician applies the
      antiparasiticide onto the skin. 1457 veterinarians (86%) administer compounds
      against adult fleas and their developmental stages also in the animal's
      environment.

PMID- 17009723
TI  - [Mesenchymal tumor in a female chamois. A case report].
AB  - A free-living 15-year old female chamois was shot because of illness and
      emaciation. The examination of the internal organs revealed numerous firm whitish
      tumour nodules in liver,spleen, mesenterium and peritoneum. Histologically the
      nature of tumour cells was identified as a metastasizing malignoma of mesenchymal
      origin. In addition to the blastoma, the parasite burden of the gastrointestinal
      tract and lungs did very likely contribute to the bad bodily condition of the
      chamois.

PMID- 17009724
TI  - [The endocrine function of skeletal muscle].
AB  - Skeletal muscle has long been considered as an effector organ under the control
      of neural and humoral regulation. Recent studies indicated that skeletal muscle
      is not only an effector organ but also an endocrine organ. It is reported that
      the skeletal muscle can express, synthesis and secrete a lot of active factors,
      such as regulatory peptide, cytokine, growth factor and so on. The active factors
      play important roles not only in the growth, metabolism and motor function of
      skeletal muscle per se by paracrine/autocrine pathway but also in the function of
      peripheral tissues and organs by endocrine pathway. It is worthwhile to pay close
      attention to the significant effects of the skeletal muscle active factors on
      locomotor disease and some systemic diseases. This paper reviews the active
      factors secreted by skeletal muscles and their physiological and
      pathophysiological significance.

PMID- 17009725
TI  - [Plasticity of bone marrow mesenchymal stem cells differentiating into
      cardiomyocytes and the potential of cardiac therapeutics].
AB  - Current treatments for ischemic cardiomyopathy aim at minimizing the deteriorated
      consequences of damaged myocardium. Recent stem cell researches have provided
      major impetus for the possibility of treating heart failure by generating new
      myocardium and vascular structures. Bone marrow mesenchymal stem cells (MSCs) ,
      also referred to as marrow stromal cells, differentiate readily into
      chondrocytes, adipocytes, and osteocytes. Recent provocative data suggest that
      they can also express phenotypic characteristics of endothelial, neural, smooth
      muscle, skeletal myoblasts, and cardiac myocytes. The multilineage potential, no
      immune reaction if self-transplantation, and the relative easiness of expansion
      in culture make MSCs a promising source of cells for medical therapies. Recent
      researches demonstrate that implantation of intramyocardial MSCs can prevent
      deteriorated remodeling and improve cardiac function, although the underlying
      mechanisms need to be further clarified. This review summarized recent studies in
      the recognition of MSCs, particularly the MSC plasticity into cardiomyocytes,
      factors and signal pathways that mediate MSC differentiation, and animal studies
      as well as clinic trials of the implantation of MSCs in postinfarct myocardium.

PMID- 17009726
TI  - [The family of calsyntenins: learning and memory related genes].
AB  - Calsyntenins (Cst) comprise a family of transmembrane proteins with the unique
      potential to link extracellular proteolytic activity with intracellular Ca2+
      signaling. It is a molecular class of calcium binding protein, which can bind
      calcium ion and being involved in signal transduction and cell communication. It
      contains three members, calsyntenin-1, calsyntenin-2 and calsyntenin-3, which are
      postsynaptic membrane proteins and predominantly expressed in brain neurons. Each
      of the three calsyntenins exhibits a distinct neuronal mRNA expression pattern.
      The three calsyntenins exhibit the highest degree of structural diversity. The
      calsyntenin-1 is located in the postsynaptic membrane of CNS synapses and a
      proteolytically processed protein of the postsynaptic membrane with a calcium
      binding cytoplasmic domain. Calsyntenin-1 is a dynamic modulator of postsynaptic
      calcium by extracellular proteolysis. Calsyntenin-1 may modulate Ca2+ transients
      locally either beneath the postsynaptic membrane or around intracellular Ca2+
      stores, such as LTP and LTD. Recent studies showed that impairment of the
      coordinated metabolic regulation of APP and calsyntenins and the consequent loss
      of the reciprocal regulation by APP and calsyntenins in the gene transactivation
      could lead to neural disorders and disease progression in AD. This is important
      to disclose the mechanism of AD and develop new drugs for treating AD.

PMID- 17009727
TI  - [The role of SM22 alpha in cytoskeleton organization and vascular remodeling].
AB  - Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays a key role in
      vascular remodeling diseases, such as atherosclerosis, hypertension and
      restenosis. Recent researches have focused on the expression regulation of VSMC
      specific marker genes and cytoskeleton organization in association with
      phenotypic modulation of VSMCs. Smooth muscle 22 alpha (SM22 alpha) is a novel
      differentiated VSMC marker, which is characterized by its smooth muscle tissue
      specific and VSMC phenotype-specific expression pattern, and serves as an actin
      association protein to participate in VSMC cytoskeleton organization and vascular
      remodeling. This article reviews recent advances in the characterization of SM22
      alpha structure and its mechanism in VSMC cytoskeleton organization and vascular
      remodeling.

PMID- 17009728
TI  - [Research on physiological and pathophysiological functions of calreticulin].
AB  - Calreticulin (CRT) is an essential Ca2+-binding /storage chaperone resident
      protein of endoplasmic reticulum or sarcoplasmic reticulum found across a diverse
      range of species. The protein is involved in the regulation of intracellular Ca2+
      homeostasis and endoplasmic reticulum Ca2+ storage capacity, and is also an
      important molecular chaperone involved in "quality control" within secretory
      pathways. Playing an important role in apoptosis, cell adhesion, gene expression
      and autoimmunity, calreticulin is involved in the genesis, development and
      prognosis of many diseases. Now we summarized the physiological function of CRT
      and its expression changes during myocardial hypertrophy, heart failure,
      angiogenesis, stresses and many other pathological conditions.

PMID- 17009729
TI  - [Perilipin associated with lipid droplets regulates lipolysis].
AB  - Perilipins are the proteins associating with the lipid droplets in adipocytes and
      steroidogenic cells. Unphosphorylated perilipins coat the surface of
      intracellular lipid droplets to form a barrier that prevents lipase from
      accessing to triacylglycerol core, thus suppressing lipolysis. Upon activation of
      protein kinase A (PKA), two proteins, hormone-sensitive lipase (HSL) and
      perilipins, are phosphorylated. The phosphorylated perilipin is required for
      inducing the translocation of HSL from the cytosol to the lipid droplets of
      adipocytes and is essential for the initiation of lipolytic reaction. It is
      proposed that phosphorylation of perilipin is a key step for the activation of
      lipolytic cascade via PKA and ERK signaling pathways. Dysregulation of perilipin
      involves in the pathogenesis of obesity, diabetes and atherosclerosis.

PMID- 17009730
TI  - [The contradictory roles of adenosine A2a receptors: protection or aggravation?].

PMID- 17009731
TI  - [Polymorphisms of beta2-adrenergic receptor].

PMID- 17009732
TI  - [The interaction between Toll-like receptors and nucleotide-binding
      oligomerization domain proteins in defensive responses].

PMID- 17009733
TI  - [Cerebral microvascular changes after cerebral ischemia].

PMID- 17009734
TI  - [Progress in the mechanisms of amyloid beta-protein inhibiting hippocampal long
      term potentiation].

PMID- 17009735
TI  - [The function of MAG in myelin development and axonal growth].

PMID- 17009736
TI  - [Mechanism of action of GDNF on dopaminergic neurons: an update].

PMID- 17009737
TI  - [Hypoxia inducible factor-1 and its role in ischemic cardiac disease].

PMID- 17009738
TI  - [The components and functions of the ubiquitin-proteasome pathway].

PMID- 17009739
TI  - [Immune responses and vaccine against systemic Candida albicans infection].

PMID- 17009740
TI  - [AGS3 proteins and heterotrimeric GTP-binding proteins signal transduction].

PMID- 17009741
TI  - [A key transcription regulator of glycolysis and lipogenesis-related genes:
      carbohydrate responsive element-binding protein].

PMID- 17009742
TI  - [Caveolin-3 and myocardial hypertrophy caused by hypertension].

PMID- 17009743
TI  - [The mechanism of vascular cell apoptosis induced by oxysterols].

PMID- 17009744
TI  - [Update of the signal transduction pathway of nephrin and its regulation
      mechanism].

PMID- 17009745
TI  - [Study on expression and functions of BMPs in nervous system].

PMID- 17009746
TI  - [Brain imaging studies and its experimental paradigm on cognitive components
      before motor execution].

PMID- 17009747
TI  - [Mitochondrial serine protease Omi/HtrA2 and apoptosis].

PMID- 17009748
TI  - Census error and the detection of density dependence.
AB  - 1. Studies aiming to identify the prevalence and nature of density dependence in
      ecological populations have often used statistical analysis of ecological time
      series of population counts. Such time-series are also being used increasingly to
      parameterize models that may be used in population management. 2. If time-series
      contain measurement errors, tests that rely on detecting a negative relationship
      between log population change and population size are biased and prone to
      spuriously detecting density dependence (Type I error). This is because the
      measurement error in density for a given year appears in the corresponding change
      in population density, with equal magnitude but opposite sign. 3. This effect
      introduces bias that may invalidate comparisons of ecological data with density
      independent time-series. Unless census error can be accounted for, time-series
      may appear to show strongly density-dependent dynamics, even though the density
      dependent signal may in reality be weak or absent. 4. We distinguish two forms of
      census error, both of which have serious consequences for detecting density
      dependence. 5. First, estimates of population density are based rarely on exact
      counts, but on samples. Hence there exists sampling error, with the level of
      error depending on the method employed and the number of replicates on which the
      population estimate is based. 6. Secondly, the group of organisms measured is
      often not a truly self-contained population, but part of a wider ecological
      population, defined in terms of location or behaviour. Consequently, the
      subpopulation studied may effectively be a sample of the population and spurious
      density dependence may be detected in the dynamics of a single subpopulation. In
      this case, density dependence is detected erroneously, even if numbers within the
      subpopulation are censused without sampling error. 7. In order to illustrate how
      process variation and measurement error may be distinguished we review data sets
      (counts of numbers of birds by single observers) for which both census error and
      long-term variance in population density can be estimated. 8. Tests for density
      dependence need to obviate the problem that measured population sizes are
      typically estimates rather than exact counts. It is possible that in some cases
      it may be possible to test for density dependence in the presence of unknown
      levels of census error, for example by uncovering nonlinearities in the density
      response. However, it seems likely that these may lack power compared with
      analyses that are able to explicitly include census error and we review some
      recently developed methods.

PMID- 17009749
TI  - Ecosystem alteration modifies the relative strengths of bottom-up and top-down
      forces in a herbivore population.
AB  - 1. Ecosystem alterations can affect the abundance, distribution and diversity of
      plants and animals, and thus potentially change the relative strength of bottom
      up (the plant resource) and top-down (natural enemies) trophic forces acting on
      herbivore populations. 2. The hypothesis that alterations of the forest ecosystem
      associated with precommercial thinning have contributed to the increased severity
      of outbreaks of Neodiprion abietis (Harris), a sawfly defoliator, through the
      reduction of trophic forces acting on N. abietis larvae, was tested using
      exclusion techniques. 3. The relative contributions to N. abietis larval
      mortality of bottom-up and top-down forces both increased with increasing levels
      of defoliation and were both reduced by thinning. The reduction of bottom-up and
      top-down forces caused a 58% mean increase in N. abietis larval survival in
      thinned compared with untreated stands, which is less than would be expected by
      the sum of the effects of thinning on each source of mortality. Evidence
      indicates that the partly compensatory, partly additive nature of the mortality
      associated with trophic forces in the system under study is responsible for this
      discrepancy. 4. To our knowledge, this is the first study to show the impact of
      ecosystem alterations on the balance between bottom-up and top-down forces acting
      on an eruptive herbivore population along a gradient of host-plant defoliation,
      and how this can lead to increased outbreak severity. It is stressed that
      accurate estimates of the relative contributions of bottom-up and top-down forces
      to mortality cannot be obtained if the additive or compensatory nature of the
      mortality associated with these trophic forces is overlooked.

PMID- 17009750
TI  - Resource partitioning in sympatric delphinids: space use and habitat preferences
      of Australian snubfin and Indo-Pacific humpback dolphins.
AB  - 1. Many species of delphinids co-occur in space and time. However, little is
      known of their ecological interactions and the underlying mechanisms that mediate
      their coexistence. 2. Snubfin Orcaella heinsohni, and Indo-Pacific humpback
      dolphins Sousa chinensis, live in sympatry throughout most of their range in
      Australian waters. I conducted boat-based surveys in Cleveland Bay, north-east
      Queensland, to collect data on the space and habitat use of both species. Using
      Geographic Information Systems, kernel methods and Euclidean distances I
      investigated interspecific differences in their space use patterns, behaviour and
      habitat preferences. 3. Core areas of use (50% kernel range) for both species
      were located close to river mouths and modified habitat such as dredged channels
      and breakwaters close to the Port of Townsville. Foraging and travelling
      activities were the dominant behavioural activities of snubfin and humpback
      dolphins within and outside their core areas. 4. Their representative ranges (95%
      kernel range) overlapped considerably, with shared areas showing strong
      concordance in the space use by both species. Nevertheless, snubfin dolphins
      preferred slightly shallower (1-2 m) waters than humpback dolphins (2-5 m).
      Additionally, shallow areas with seagrass ranked high in the habitat preferences
      of snubfin dolphins, whereas humpback dolphins favoured dredged channels. 5.
      Slight differences in habitat preferences appear to be one of the principal
      factors maintaining the coexistence of snubfin and humpback dolphins. I suggest
      diet partitioning and interspecific aggression as the major forces determining
      habitat selection in these sympatric species.

PMID- 17009751
TI  - The ecology of motherhood: the structuring of lactation costs by chacma baboons.
AB  - 1. Data from a long-term study of Papio hamadryas ursinus (L.) in the De Hoop
      Nature Reserve, Western Cape, South Africa, were used to test the assumptions and
      predictions of Altmann's model of maternal time budgets. 2. Female baboons'
      feeding time was below model predictions, and there was no evidence for a
      consistent increase in feeding time with infant age. In addition, female feeding
      time was not significantly higher than observed baseline feeding times for
      nonlactating females. 3. Female baboons reduced activity levels in the first few
      months post-partum, as reflected in significant increases in resting time, and
      there was some indication that females lost body mass over the course of
      lactation. When feeding demand was high, females sacrificed social time, and
      conserved resting time. 4. Females increased vigilance levels during the first 4
      months of infant life and were more vigilant overall during lactation than when
      nonlactating. There was a negative relationship between feeding time and
      vigilance, but a positive relationship between resting time and vigilance. 5.
      Female baboons at De Hoop appear to cope with the energetic costs of lactation by
      reducing activity levels, although this cannot compensate completely for
      increased energetic costs. This may not be so much an'energy-sparing' strategy as
      a response to threats presented by infanticidal males in this population. Females
      therefore trade-off feeding time against vigilance.

PMID- 17009752
TI  - Application of random effects to the study of resource selection by animals.
AB  - 1. Resource selection estimated by logistic regression is used increasingly in
      studies to identify critical resources for animal populations and to predict
      species occurrence. 2. Most frequently, individual animals are monitored and
      pooled to estimate population-level effects without regard to group or individual
      level variation. Pooling assumes that both observations and their errors are
      independent, and resource selection is constant given individual variation in
      resource availability. 3. Although researchers have identified ways to minimize
      autocorrelation, variation between individuals caused by differences in selection
      or available resources, including functional responses in resource selection,
      have not been well addressed. 4. Here we review random-effects models and their
      application to resource selection modelling to overcome these common limitations.
      We present a simple case study of an analysis of resource selection by grizzly
      bears in the foothills of the Canadian Rocky Mountains with and without random
      effects. 5. Both categorical and continuous variables in the grizzly bear model
      differed in interpretation, both in statistical significance and coefficient
      sign, depending on how a random effect was included. We used a simulation
      approach to clarify the application of random effects under three common
      situations for telemetry studies: (a) discrepancies in sample sizes among
      individuals; (b) differences among individuals in selection where availability is
      constant; and (c) differences in availability with and without a functional
      response in resource selection. 6. We found that random intercepts accounted for
      unbalanced sample designs, and models with random intercepts and coefficients
      improved model fit given the variation in selection among individuals and
      functional responses in selection. Our empirical example and simulations
      demonstrate how including random effects in resource selection models can aid
      interpretation and address difficult assumptions limiting their generality. This
      approach will allow researchers to appropriately estimate marginal (population)
      and conditional (individual) responses, and account for complex grouping,
      unbalanced sample designs and autocorrelation.

PMID- 17009753
TI  - Habitat shape, metapopulation processes and the dynamics of multispecies predator
      prey interactions.
AB  - 1. The effects of habitat shape, connectivity and the metapopulation processes of
      persistence and extinction are explored in a multispecies resource-consumer
      interaction. 2. The spatial dynamics of the indirect interaction between two prey
      species (Callosobruchus chinensis, Callosobruchus maculatus) and a predator
      (Anisopteromalus calandrae) are investigated and we show how the persistence time
      of this interaction is altered in different habitat configurations by the
      presence of an apparent competitor. 3. Habitat structure has differential effects
      on the dynamics of the resource-consumer interaction. Across all habitat types,
      the pairwise interaction between C. chinensis and A. calandrae is highly prone to
      extinction, while the interaction between C. maculatus and A. calandrae shows
      sustained long-term fluctuations. Contrary to expectations from theory, habitat
      shape has no significant effect on persistence time of the full, three-species
      resource-consumer assemblage. 4. A stochastic metapopulation model for a range of
      habitat configurations, incorporating different forms of regulatory processes,
      highlights that it is the spatially explicit population dynamics rather than the
      shape of the metapopulation that is the principal determinant of interaction
      persistence time.

PMID- 17009754
TI  - Mitigating human disturbance: can protection influence trajectories of recovery
      in benthic assemblages?
AB  - 1. Understanding whether Marine Protected Areas (MPAs) can be considered as a
      suitable tool for restoring the structure and function of populations and
      assemblages is urgently needed to achieve an effective policy of mitigation of
      human impact in coastal management. However, to date, the role played by MPAs in
      enhancing ecosystems resilience has been more advocated than unambiguously
      documented. 2. This study was designed to test whether full protection in marine
      reserves facilitates recovery of benthos impacted by the date mussel Lithophaga
      lithophaga fishery, one of the most harmful human activities affecting subtidal
      rocky habitats in the Mediterranean Sea. 3. The effects of this destructive
      fishery were reproduced at one fully protected location (P) and at two
      unprotected control locations (Cs) in the SW Mediterranean Sea. At each location,
      three plots (4 m2) of rocky surface at 4-6 m depth were disturbed experimentally,
      while another three plots served as reference. In each plot, the species
      composition and relative cover of the sessile benthic assemblages were sampled
      photographically on each of five occasions during a period of 20 months. 4. Over
      and above variation in habitat features among locations, multivariate and
      univariate analyses revealed significant differences between P-vs.-Cs in patterns
      of assemblage recovery and showed that, at the fully protected location, recovery
      was faster than at the unprotected control locations. 5. Our results suggest that
      MPAs have the potential to change the trajectories of recovery of disturbed
      assemblages by accelerating the processes of recolonization and call for further
      investigation to identify the specific mechanisms underlying increased
      resilience.

PMID- 17009755
TI  - Consequences of heterogeneity in survival probability in a population of Florida
      scrub-jays.
AB  - 1. Using data on breeding birds from a 35-year study of Florida scrub-jays
      Aphelocoma coerulescens (Bosc 1795), we show that survival probabilities are
      structured by age, birth cohort, and maternal family, but not by sex. Using both
      accelerated failure time (AFT) and Cox proportional hazard models, the data are
      best described by models incorporating variation among birth cohorts and greater
      mortality hazard with increasing age. AFT models using Weibull distributions with
      the shape parameter > 1 were always the best-fitting models. 2. Shared frailty
      models allowing for family structure greatly reduce model deviance. The best
      fitting models included a term for frailty shared by maternal families. 3. To ask
      how long a data set must be to reach qualitatively the same conclusions, we
      repeated the analyses for all possible truncated data sets of 2 years in length
      or greater. Length of the data set affects the parameter estimates, but not the
      qualitative conclusions. In all but three of 337 truncated data sets the best
      fitting models pointed to same conclusions as the full data set. Shared frailty
      models appear to be quite robust. 4. The data are not adequate for testing
      hypotheses as to whether variation in frailty is heritable. 5. Substantial
      structured heterogeneity for survival exists in this population. Such structured
      heterogeneity has been shown to have substantial effects in reducing demographic
      stochasticity.

PMID- 17009756
TI  - Asymmetric coexistence: bidirectional abiotic and biotic effects between goose
      barnacles and mussels.
AB  - 1. Species coexistence depends on the net effect of interacting species,
      representing the sum of multiple interaction components that may act
      simultaneously and vary independently depending on ambient environmental
      conditions. Consequently, for a comprehensive understanding of the compound
      nature of species interactions and coexistence, a mechanistic approach that
      allows a separate evaluation of each interaction component is required. 2. Two
      sessile filter-feeders, the goose barnacle Capitulum mitella and the mussel
      Septifer virgatus, coexist on moderately wave-exposed rocky shores in south
      western Japan. In the upper intertidal, Capitulum positively influenced Septifer
      survivorship and growth through amelioration of thermal stress and of physical
      disturbance. On the other hand, these species are potential competitors as they
      have similar body sizes and modes of resource utilization. These opposite
      processes, facilitation and competition, are based on abiotic characteristics and
      biotic functions of the two species, respectively. 3. In order to quantify the
      bidirectional abiotic, biotic and net effects, a series of experimental
      manipulations was conducted involving the use of living neighbours with both
      abiotic and biotic effects, and artificial mimics to simulate abiotic effects
      without biotic effects. 4. Capitulum had strong positive abiotic effects on the
      mussel survivorship in most experimental periods, while the biotic effect was
      negligible or weakly negative, suggesting that the net effect of Capitulum on
      mussel survival was largely attributable to the abiotic effect. In contrast, a
      significantly negative biotic effect on the mussel growth rate was always
      present, though this was cancelled out by the larger, positive abiotic effect. In
      the case of Septifer, its abiotic and biotic effects on the survivorship of goose
      barnacles were negligible, while those on the growth rate showed temporal
      variation. 5. With respect to the relationship between species interaction and
      environmental conditions, the strength of abiotic facilitative effect of
      Capitulum on mussel survival increased with increasing abiotic stress, while the
      strength of biotic effect was negligible or weakly negative. As regards the
      effects of mussels on goose barnacles, our study indicated no obvious
      relationship. These results point to the importance of decomposing interaction
      for an accurate, mechanistic understanding of species relations and coexistence.

PMID- 17009757
TI  - Nest ornamentation by female spotless starlings in response to a male display: an
      experimental study.
AB  - 1. The use of behavioural traits by females in signalling condition has been
      practically ignored in evolutionary theory. However, females may also exhibit
      ornaments and behavioural displays, although less elaborated than those of males.
      2. In this study we suggest that the carrying of feathers by spotless starlings
      Sturnus unicolor Temminck females to decorate the nest represents an elaborated
      and costly behaviour that is displayed in response to a courtship male behaviour:
      the carrying of nest green plants. 3. By experimentally increasing the amount of
      green plants in the nests, to give the appearance that highly attractive males
      defended them, we induced females to increase their feather carrying rates. 4.
      The amount of feathers carried to the nest was correlated to female reproductive
      experience and laying date, two variables correlated with female body condition.
      These results suggests that this behaviour may work as an honest indicator of
      female quality. 5. We conclude that male carrying plants and female carrying
      feathers can be viewed as two sex-specific functionally related signalling
      behaviours involved in mutual courtship or status signalling.

PMID- 17009758
TI  - A functional response model of a predator population foraging in a patchy
      habitat.
AB  - 1. Functional response models (e.g. Holling's disc equation) that do not take the
      spatial distributions of prey and predators into account are likely to produce
      biased estimates of predation rates. 2. To investigate the consequences of
      ignoring prey distribution and predator aggregation, a general analytical model
      of a predator population occupying a patchy environment with a single species of
      prey is developed. 3. The model includes the density and the spatial distribution
      of the prey population, the aggregative response of the predators and their
      mutual interference. 4. The model provides explicit solutions to a number of
      scenarios that can be independently combined: the prey has an even, random or
      clumped distribution, and the predators show a convex, sigmoid, linear or no
      aggregative response. 5. The model is parameterized with data from an acarine
      predator-prey system consisting of Phytoseiulus persimis and Tetranychus urticae
      inhabiting greenhouse cucumbers. 6. The model fits empirical data quite well and
      much better than if prey and predators were assumed to be evenly distributed
      among patches, or if the predators were distributed independently of the prey. 7.
      The analyses show that if the predators do not show an aggregative response it
      will always be an advantage to the prey to adopt a patchy distribution. On the
      other hand, if the predators are capable of responding to the distribution of
      prey, then it will be an advantage to the prey to be evenly distributed when its
      density is low and switch to a more patchy distribution when its density
      increases. The effect of mutual interference is negligible unless predator
      density is very high. 8. The model shows that prey patchiness and predator
      aggregation in combination can change the functional response at the population
      level from type II to type III, indicating that these factors may contribute to
      stabilization of predator-prey dynamics.

PMID- 17009759
TI  - Intraguild predation reduces redundancy of predator species in multiple predator
      assemblage.
AB  - 1. Interference between predator species frequently decreases predation rates,
      lowering the risk of predation for shared prey. However, such interference can
      also occur between conspecific predators. 2. Therefore, to understand the
      importance of predator biodiversity and the degree that predator species can be
      considered functionally interchangeable, we determined the degree of additivity
      and redundancy of predators in multiple- and single-species combinations. 3. We
      show that interference between two invasive species of predatory crabs, Carcinus
      maenas and Hemigrapsus sanguineus, reduced the risk of predation for shared
      amphipod prey, and had redundant per capita effects in most multiple- and single
      species predator combinations. 4. However, when predator combinations with the
      potential for intraguild predation were examined, predator interference increased
      and predator redundancy decreased. 5. Our study indicates that trophic structure
      is important in determining how the effects of predator species combine and
      demonstrates the utility of determining the redundancy, as well as the
      additivity, of multiple predator species.

PMID- 17009760
TI  - Quantitative analysis of dental microwear in threespine stickleback: a new
      approach to analysis of trophic ecology in aquatic vertebrates.
AB  - 1. The threespine stickleback Gasterosteus aculeatus is an important model
      organism in studies of genomic and phenotypic evolution, adaptation and
      speciation. Fossil Gasterosteus offer the potential to test models derived from
      studies of extant fishes over true evolutionary time-scales. Competition for food
      resources, for example, plays an important part in stickleback speciation,
      causing divergence in food gathering traits and ecological character
      displacement, but it is not possible to test this model in fossils because
      evidence of diet is almost never preserved. 2. We demonstrate here that
      quantitative analysis of dental microwear, a technique previously applied only to
      mammals, provides a reliable guide to the dietary preferences of stickleback.
      Teeth from stickleback raised under laboratory conditions exhibit microwear
      patterns that vary systematically according to substrate coarseness and whether
      fishes feed on Daphnia within the water column, or on chironomid larvae from the
      bottom. Furthermore, microwear data exhibit a progressive shift in their
      distribution that tracks differences in experimental feeding treatments. 3.
      Microwear in wild populations also exhibits a relationship with feeding. In blind
      assessments of trophic niche based on microwear patterns we were able to
      correctly assign all but one equivocal population to trophic group. Microwear
      data from wild stickleback exhibit a shift in distribution comparable with that
      observed across the range of treatments in the laboratory and these allow
      populations to be ranked according to the degree to which they approach fully
      benthic or fully limnetic feeding. 4. Our results demonstrate that microwear has
      the potential to be a powerful tool in the analysis of fish trophic ecology,
      particularly in the analysis of species pairs and niche differentiation. It has
      advantages over the trophic snapshot provided by analysis of stomach contents in
      that microwear reflects feeding and food preferences over a longer period of
      time, and can be applied where these data are unavailable. Furthermore, it is
      applicable to extinct organisms and fossils, allowing the role of trophic
      ecology, niche partitioning and competition over evolutionary time-scales to be
      investigated for the first time.

PMID- 17009761
TI  - Patterns of growth and body condition in sea otters from the Aleutian archipelago
      before and after the recent population decline.
AB  - 1. Growth models for body mass and length were fitted to data collected from 1842
      sea otters Enhydra lutris shot or live-captured throughout south-west Alaska
      between 1967 and 2004. Growth curves were constructed for each of two main year
      groups: 1967-71 when the population was at or near carrying capacity and 1992-97
      when the population was in steep decline. Analyses of data collected from animals
      caught during 2004, when the population density was very low, were precluded by a
      small sample size and consequently only examined incidentally to the main growth
      curves. 2. Growth curves demonstrated a significant increase in body mass and
      body length at age in the 1990s. Asymptotic values of body mass were 12-18%
      higher in the 1990s than in the 1960s/70s, and asymptotic values for body length
      were 10-11% higher between the same periods. Data collected in 2004 suggest a
      continued increase in body size, with nearly all data points for mass and length
      falling significantly above the 1990s growth curves. 3. In addition to larger
      asymptotic values for mass and length, the rate of growth towards asymptotic
      values was more rapid in the 1990s than in the 1960s/70s: sea otters reached 95%
      of asymptotic body mass and body length 1-2 years earlier in the 1990s. 4. Body
      condition (as measured by the log mass/log length ratio) was significantly
      greater in males than in females. There was also an increasing trend from the
      1960s/70s through 2004 despite much year-to-year variation. 5. Population age
      structures differed significantly between the 1960s/70s and the 1990s with the
      latter distribution skewed toward younger age classes (indicating an altered lx
      function) suggesting almost complete relaxation of age-dependent mortality
      patterns (i.e. those typical of food-limited populations). 6. This study spanned
      a period of time over which the population status of sea otters in the Aleutian
      archipelago declined precipitously from levels at or near equilibrium densities
      at some islands in the 1960s/70s to < 5% of estimated carrying capacity by the
      late 1990s. The results of this study indicate an improved overall health of sea
      otters over the period of decline and suggest that limited nutritional resources
      were not the cause of the observed reduced population abundance. Our findings are
      consistent with the hypothesis that the decline was caused by increased killer
      whale predation.

PMID- 17009762
TI  - Experimental and model analyses of the effects of competition on individual size
      variation in wood frog (Rana sylvatica) tadpoles.
AB  - 1. Size variation is a ubiquitous feature of animal populations and is predicted
      to strongly influence species abundance and dynamics; however, the factors that
      determine size variation are not well understood. 2. In a mesocosm experiment, we
      found that the relationship between mean and variation in wood frog (Rana
      sylvatica) tadpole size is qualitatively different at different levels of
      competition created by manipulating resource supply rates or tadpole density. At
      low competition, relative size variation (as measured by the coefficient of
      variation) decreased as a function of mean size, while at high competition,
      relative size variation increased. Therefore, increased competition magnified
      differences in individual performance as measured by growth rate. 3. A model was
      developed to estimate the contribution of size-dependent factors (i.e. based on
      size alone) and size-independent factors (i.e. resulting from persistent inherent
      phenotypic differences other than size that affect growth) on the empirical
      patterns. 4. Model analysis of the low competition treatment indicated that size
      dependent factors alone can describe the relationship between mean size and size
      variation. To fit the data, the size scaling exponent that describes the
      dependence of growth rate on size was determined. The estimated value, 0-83, is
      in the range of that derived from physiological studies. 5. At high competition,
      the model analysis indicated that individual differences in foraging ability,
      either size-based or due to inherent phenotypic differences (size-independent
      factors), were much more pronounced than at low competition. The model was used
      to quantify the changes in size-dependent or size-independent factors that
      underlie the effect of competition on size-variation. In contrast to results at
      low competition, parameters derived from physiological studies could not be used
      to describe the observed relationships. 6. Our experimental and model results
      elucidate the role of size-dependent and size-independent factors in the
      development of size variation, and highlight and quantify the context dependence
      of individual (intrapopulation) differences in competitive abilities.

PMID- 17009763
TI  - The paradoxical effects of nutrient ratios and supply rates on an outbreaking
      insect herbivore, the Australian plague locust.
AB  - 1. The Australian plague locust, Chortoicetes terminifera, develops following
      rainfall in an environment dominated by two host plants, the annual
      Dactyloctenium radulans and the perennial Astrebla lappacea. This simple system
      provides an ideal opportunity to explore the relationship between plant quality,
      individual herbivore performance and population responses. 2. We compared the two
      grasses chemically and structurally, and the behavioural, physiological and
      developmental responses of locust nymphs to these diets. 3. The grasses appeared
      to be of similar nutritional quality in terms of their chemical composition,
      although they differed in their physical properties. Early instar nymphs
      performed equally well on both grasses. However, older nymphs consuming D.
      radulans developed faster, survived better and attained a higher body weight
      compared with those consuming A. lappacea. 4. The differences in performance by
      the older nymphs related to the rate and ratio of supply of carbohydrate and
      protein from the two grasses, with less carbohydrate being assimilated from A.
      lappacea than D. radulans per unit of protein assimilated. Experiments showed
      that these differences arose as a direct result of the physical barrier to
      nutrient extraction provided by cell walls and indirectly through the amount of
      water contained within each cell. Paradoxically, nitrogen did not limit
      performance in the traditional sense through shortage,but rather its relative
      excess in A. lappacea appeared to impede intake and assimilation of adequate
      carbohydrate. 5. As a consequence, we predict that the length of time D. radulans
      remains available following rainfall will influence plaguing dynamics, although
      not for the reasons previously thought. 6. The results highlight the need to
      consider nutrient balance and actual rates of supply (rather than simply
      measuring the chemical composition of the plant) when attempting to understand
      herbivore nutritional ecology.

PMID- 17009764
TI  - Species richness and allometric scaling jointly determine biomass in model
      aquatic food webs.
AB  - 1. Allometric theory makes specific predictions about how density, and
      consequently biomass, scale with organism size within trophic levels, across
      trophic levels and across food webs. 2. Diversity-yield relationships suggest
      that more diverse food webs can sometimes support more biomass through mechanisms
      involving niche complementarity or selection effects that are sometimes
      attributed to organism size. 3. We combine the above two approaches and show
      that, generally, density and biomass scale with organism size within and between
      trophic levels as predicted by allometric theory. Further, food webs converged in
      total biomass despite persistent differences in the composition and size of the
      organisms among food webs; species richness explained deviations from the
      constant yield of biomass expected from size-abundance relationships. 4. Our
      results suggest that organism size plays only a transient role in controlling
      community biomass because population increases or decreases lead to rapid
      convergence in biomass. Species richness affects community biomass independently
      by effectively increasing the mass of organisms that can be supported in a given
      productivity regime.

PMID- 17009765
TI  - Sensitivity analysis of Markov models for communities of competing sessile
      organisms.
AB  - 1. Communities of competing sessile organisms are often modelled using Markov
      chains. Sensitivity analysis of the stationary distribution of these models tells
      us how we expect the abundance of each organism to respond to changes in
      interactions between species. This is important for conservation and management.
      2. Markov models for such communities have usually been formulated in discrete
      time. Each column of the discrete-time transition matrix must sum to 1 (column
      stochasticity). Sensitivity analysis therefore involves defining a pattern of
      compensation that maintains column stochasticity as a single transition
      probability changes. There is little biological theory about the appropriate
      compensation pattern, but the usual choices involve changing only the elements of
      a single column of the transition matrix. 3. I argue that if the underlying
      dynamics occur in continuous time, each transition probability is the net outcome
      of direct and many indirect interactions. 4. Determining the consequences of
      changing a single direct interaction will often be of interest. I show how this
      can be achieved using a continuous-time model. The resulting discrete-time
      compensation pattern is quite different from those that have been considered
      elsewhere, with changes occurring in many columns. 5. I also show how to
      determine which direct interactions are being changed under any discrete-time
      compensation pattern.

PMID- 17009766
TI  - Testing mechanisms of coexistence among two species of frugivorous primates.
AB  - 1. We examined mechanisms of coexistence between two congeneric species of
      frugivorous primates, the blue monkey (Cercopithecus mitis) and the red-tailed
      monkey (C. ascanius). 2. We used giving-up densities (the amount of food which
      animals leave in a patch) in fruit trees to measure foraging efficiency and to
      evaluate possible mechanisms of coexistence. Animals with higher giving-up
      densities are less likely to persist in the company of those with lower giving-up
      densities because the former are not able to exploit food patches used previously
      by the latter. We climbed trees to estimate giving-up densities by counting the
      fruit which primates left behind. 3. We tested five possible mechanisms of
      coexistence. Three mechanisms proposed that each frugivorous species has a lower
      giving-up density than the other in at least one of the following: (1) different
      tree species, (2) within-tree foraging zones or (3) seasons. The fourth mechanism
      predicted that the socially dominant species exploits resources first and that
      the subordinate species has lower giving-up densities. The final mechanism
      predicted that one species would find resources more quickly than the other,
      which would in turn have a lower giving-up density. 4. Four of the five
      mechanisms received no support from our data. Only a trade-off between
      interspecific dominance and giving-up densities was supported. 5. We discuss the
      generality of our results and possible interactions with other factors.

PMID- 17009767
TI  - Treatment integrity in a home-based pre-reading intervention programme.
AB  - Treatment integrity is an underexposed issue in the phonological awareness
      intervention research. The current study assessed the integrity of treatment of
      the families (N = 32) participating in the experimental condition of a home-based
      pre-reading intervention study. The participating kindergartners were all
      genetically at risk for developing dyslexia. Two aspects of treatment integrity,
      the number of lessons completed (quantity) and the quality of the administration
      of the programme (observed in a videotaped session), were investigated. The level
      of treatment integrity turned out to be 66% when completion of all lessons was
      taken as quantitative criterion, and about 74% when quality of the parent-child
      interaction was assessed. The two measures could predict the pre-reading skills
      at the end of kindergarten. Together they accounted for 43% of the variance in
      this dependent variable. Together with pre-reading scores at the pre-test the
      total predicted variance was 87%. The number of lessons completed still
      contributed 12% to the prediction after controlling for pre-test scores. The
      results indicated that treatment integrity indeed appears to be an important
      aspect of treatment outcome and should therefore be included in intervention
      studies.

PMID- 17009768
TI  - Verbatim and gist recall of sentences by dyslexic and non-dyslexic adults.
AB  - Forty-eight college students, 24 of them dyslexic, were presented with four
      sentences of increasing complexity. Participants were asked to repeat each
      sentence and a record was kept of the number of repetitions required before 100%
      correct accuracy was achieved. None of the 24 control participants required a
      total of more than eight repetitions over the four sentences, whereas among the
      dyslexics the total number of repetitions needed ranged from one to 25. Dyslexic
      participants were unpredictable in their performance from one level of difficulty
      to the next and inter-individual variability was far greater in the dyslexic
      group than in the control group. Overall, despite their relatively poor
      performance in achieving verbatim accuracy relative to non-dyslexic participants,
      dyslexic individuals regularly managed to preserve the gist of the sentences.
      Some theoretical issues arising from these results are discussed.

PMID- 17009769
TI  - Meta-analysis of the nonword reading deficit in specific reading disorder.
AB  - A meta-analysis was conducted to investigate whether specific reading disorder
      (SRD) groups demonstrate a deficit in using phonological recoding strategies.
      Thirty-four studies were reviewed that had compared the nonword reading
      performances of SRD groups with reading-level matched (RL) control groups. The
      average nonword reading difference between groups across the total number of
      studies was moderate (d = 0.65, N = 2865). Three predictors of the size of group
      differences in nonword reading ability were identified. Studies that used passage
      reading tests to match groups for reading level found significantly less evidence
      for nonword reading deficits than studies that used word-level reading accuracy
      tests. Secondly, there was a significant positive relationship between group
      differences in intelligence level (SRD-RL control group) and effect sizes.
      Finally, group differences in age showed a significant negative association with
      effect magnitudes. The mean age, reading level and intelligence level of groups
      did not significantly predict nonword reading outcomes. It was concluded that
      there was evidence for nonword reading deficits in SRD groups, consistent with
      the claim that deficient development of phonological recoding strategies is a
      leading cause of reading difficulties.

PMID- 17009770
TI  - Young minds.

PMID- 17009771
TI  - Welcoming diversity.

PMID- 17009772
TI  - Overweight children: the role of the public health practitioner.

PMID- 17009773
TI  - Venous ulcer.

PMID- 17009774
TI  - Parents' views of a Family Health Assessment.
AB  - This paper reports on a qualitative study that was undertaken to evaluate a
      structured health needs assessment, the Family Health Assessment (FHA), from the
      perspective of parents with pre-school children. Nine mothers were involved in
      two focus group discussions. Some of the mothers reported that using the FHA with
      a health visitor had been a positive experience because it had enabled them to
      identify their health needs and access appropriate advice and support. Other
      mothers, however, did not find the FHA particularly useful as they did not feel
      that the FHA was relevant to them at the time and they were unclear about why
      they were being asked some of the questions. The key findings are outlined in
      relation to the current context of health visiting, which is supporting a family
      centred public health role and the limited but contemporary literature exploring
      the use of structured approaches to health needs assessment. Recommendations for
      future research and developments are made.

PMID- 17009775
TI  - Health visitor or public health nurse? A Scottish study.
AB  - The Scottish Executive and the National Health Service (NHS) have been
      consistently promoting 'public health nursing' as a new way forward in the
      community. In addition, since 2001 traditional health visitor and school nurse
      education programmes have been replaced by a single public health nurse training
      curriculum. However, many of the roles, responsibilities and job descriptions of
      clinical health visiting staff have remained unchanged within health board areas.
      This has led to apparent confusion among staff, both newly qualified and those
      already in post. This lack of clarity in policy and role prompted this research
      study, which set out to investigate the perceptions of the public health role of
      the health visitor within a health board area in Scotland. Initially, a review of
      the relevant literature was undertaken to provide in-depth background information
      on the topic, to enable a critical analysis of the current public health role of
      the health visitor. This analysis was further informed by obtaining qualitative
      and quantitative data via a questionnaire sent to 89 health visitors, to
      determine the attitudes and opinions of health visitors currently working within
      a Scottish health board area. Results from the study indicate that, despite the
      plethora of public health-related Scottish Executive publications and the changes
      in educational programmes, many health visitors still carry out what is perceived
      as a traditional role with mainly the under-five age group. The study also
      identified the need for clear direction in the public health role for health
      visitors, with many health visitors expressing a willingness to make changes to
      their current role.

PMID- 17009776
TI  - Helping fathers understand their new infant: a pilot study of a parenting
      newsletter.
AB  - This paper presents the findings of a pilot study on the views of first-time
      fathers in the northeast of England on an aged-paced parenting newsletter, and
      what being a parent means to them.A monthly newsletter for new parents, initially
      conceived in Wisconsin, USA, has been adapted for use in the UK. Each issue of
      the newsletter (named 'Baby Express') contains topics relevant to the particular
      stage of the child's life, and is delivered free to the home monthly in the first
      year and bi-monthly in the second and third years, when it is renamed Toddler
      Express'.'Baby Express' is a glossy, eight-page, easy-to-read newsletter, which
      focuses on emotional development, parent interaction and play. Topics covered
      include father-related content, such as the father's role in caring for their
      child and father-child relationships. As part of a randomised controlled study of
      new parents, fathers were invited to complete a postal questionnaire at the one
      year follow-up; 42 of 75 fathers responded (56%). The findings showed that
      fathers wanted to be more involved in caring for their child, and felt it was
      important to obtain information that would help them to do this. A total of
      37(88%) had read 'Baby Express' and all of the fathers who read it thought it was
      relevant to dads. We concluded that'Baby Express' is as effective an information
      tool for fathers as for mothers, but additional material for fathers would be
      valuable. Fathers need to be included in parenting education to a greater extent.

PMID- 17009777
TI  - Tongue tie and breastfeeding: assessing and overcoming the difficulties.
AB  - Tongue tie, a condition in which the tongue's mobility is restricted, may reduce
      the ability of babies to breastfeed successfully. In this age of mass artificial
      feeding, the management of this condition has been, until recently, overlooked.
      This article highlights the effects of tongue tie on breastfeeding and what
      health professionals should be doing to assess and manage any difficulties

PMID- 17009778
TI  - Future of the NHS pension scheme secured by new deal.

PMID- 17009779
TI  - [Small change, large effect--a new vancomycin derivative against MRSA].

PMID- 17009780
TI  - [Beta-lactam antibiotics as neuroprotectives].

PMID- 17009781
TI  - [An old pathway to new antibiotics--platensimycin].

PMID- 17009782
TI  - [Between chance and deliberate development: the history of beta-lactam
      antibiotics].

PMID- 17009783
TI  - [Actions and resistance mechanisms of beta-lactam antibiotics. Penicillin-binding
      proteins, beta-3-lactamases and signal proteins].

PMID- 17009784
TI  - [Structure-activity relationships of penicillin G to tricyclic beta-lactams].

PMID- 17009785
TI  - [The opponent, we were unable to defeat. Beta-lactamases].

PMID- 17009786
TI  - [Beta-lactam resistance hits virulence. Methicillin resistant Staphylococcus
      aureus].

PMID- 17009787
TI  - [Uses in in ambulatory and stationary situations. Clinical indications for beta
      lactams].

PMID- 17009788
TI  - [Opposition to Ehrlich's paradigm of selective toxicity. Adverse effects of beta
      lactam antibiotics].

PMID- 17009789
TI  - [What we know and what we want to know about beta-lactams. Pharmacokinetics and
      pharmacodynamics of beta lactams].

PMID- 17009790
TI  - [Less silence, please].

PMID- 17009791
TI  - [Public health series--15: Hygiene plan: Obligatory and general practice
      pertinent job fundamentals].

PMID- 17009792
TI  - [Knowledge based software solution for nursing care planning and documentation:
      uniform and reproducible recording with apenio].

PMID- 17009793
TI  - [Nursing anamnesis: more than inquiry of deficits].

PMID- 17009794
TI  - [Successful postoperative pain therapy: not only a question of medication].

PMID- 17009795
TI  - [Health promotion in nursing between demand and reality--13: Eating and
      sensuality].

PMID- 17009796
TI  - [Incidence of accidenal falls, sequelae of falls and circumstances of falls in
      the hospital: indications for prevention].

PMID- 17009797
TI  - [Health associated quality of life in home ventilation--1: In the labyrinth of
      concepts].

PMID- 17009798
TI  - [Standardized assessment instruments in nursing: possibilities and limits].

PMID- 17009799
TI  - [Assessment of need for nursing care and assistance within the scope of the
      "personal nursing budget": "we must take this step" (interview by Katrin
      Balzer)].

PMID- 17009800
TI  - [Corner stones of health care reform discussion: "factually little has changed"].

PMID- 17009801
TI  - [The personal budget in nursing care: a lever for system change].

PMID- 17009802
TI  - [The psychology of MDK (Medical Service of Public Health Insurance) examination:
      good preparation makes it a "home game"].

PMID- 17009803
TI  - [Progress in the electronic medical record--report of experiences: speaking the
      same language].

PMID- 17009804
TI  - [Minor simulation, big effect. Beds with microstimulation systems to support
      decubitus ulcer prevention].

PMID- 17009805
TI  - [From case to case: traces of aging].

PMID- 17009806
TI  - [Development and use of the ICF from the nursing point of view--a position
      statement of the German speaking working group "ICF and Nursing"].
AB  - The International Classification of Functioning, Disability and Health (ICF)
      provides a comprehensive and internationally acknowledged framework for the
      description of human functional health, which covers all aspects of health and
      some health-related elements of well-being. The ICF is part of the classification
      family of the World Health Organisation (WHO) and can be used by different health
      care disciplines as well as for different purposes. In order to promote the
      discussion about ICF within the nursing profession, the German speaking working
      group "ICF and Nursing" developed a position statement that critically reflects
      both the potentials and the restrictions of the ICF for use in nursing care,
      particularly for diagnostical purposes.

PMID- 17009807
TI  - [Glanders--a comprehensive review].
AB  - Since 1990 the number of glanders outbreaks in race, military and pleasure horses
      in Asia and South America is steadily increasing. Glanders, which is eradicated
      in Western Europe, Australia and Northern America, is currently considered a re
      emerging disease. Consequently, the disease may be introduced into glanders-free
      regions by subclinical carriers at any time. The causative agent of glanders,
      Burkholderia (B.) mallei, is highly contagious and leads to chronic disease in
      horses whereas in donkeys and mules the disease is acute and often fatal.
      Occurrence of the disease leads to international trading restrictions and
      infected animals immediately have to be culled and safely disposed off. In humans
      B. mallei infection results in a severe clinical course, and is fatal without
      appropriate therapy. Its pathogenicity makes B. mallei a potential biological
      agent that may be used in bioterroristic attacks. Due to the eradication of
      glanders in the second half of the last century, veterinarians in western
      European countries are no longer familiar with its clinical presentation in
      solipeds. Having these facts in mind, this review describes the epidemiology,
      clinical signs, pathology and the current eradication strategy of this
      interesting zoonosis. Pictures of imported endurance horses infected with
      glanders taken during an eradication campaign in Dubai, United Arab Emirates, in
      2004 illustrate most typical clinical findings.

PMID- 17009809
TI  - [Examination of the density of the brain parenchyma in different dog breeds using
      quantitative computed tomography].
AB  - In the present study quantitative computed tomography was used to analyze the
      absorption density in different localisations of the brain parenchyma
      comparatively in five different dog breeds. The breeds German Shepherd Dog,
      Dachshund, Boxer, Labrador Retriever and Miniature Poodle were chosen as
      representatives of different skull shapes and sizes. The mean absorption density
      for the German Shepherd Dog was 35.8 HU in the cerebellum, 28.5 - 34.8 HU in
      several locations of the cerebrum, 39.6 HU in the brain stem and 40.8 HU in the
      hypophyseal region. In the Dachshund, the mean density was 33.8 HU (cerebellum),
      34.3 - 44.2 HU (several locations of the cerebrum), 33.3 HU (brain stem) and 38.6
      HU (hypophyseal region). The Boxer showed a mean density of 38.7 HU in the
      cerebellum, 30.2 - 40.8 HU in several locations of the cerebrum, 35.6 HU in the
      brain stem and 33.1 HU in the hypophyseal region. The mean absorption density in
      the Labrador Retriever was 37.2 HU in the cerebellum, 29.4 - 32.9 HU (several
      locations of the cerebrum), 34.7 HU in the brain stem and 47.5 HU in the
      hypophyseal region. In the Miniature Poodle the mean density was 33.6 HU
      (cerebellum), 34.9 - 45.5 HU (several locations of the cerebrum), 32.7 HU (brain
      stem) and 32.4 HU (hypophyseal region). The study showed that the absorption
      density of the cerebrum, the brain stem and of the hypophyseal region partly were
      influenced by the different dog breeds. In the cerebellum no difference of
      density could be seen in the different breeds. The standardised values for the
      data of absorption densities of the brain parenchyma are the base for further
      examinations of dogs with clinical CNS diseases.

PMID- 17009808
TI  - [Effects of the zinc oxide and cod liver oil containing ointment Zincojecol in an
      animal model of wound healing].
AB  - The effects of Zincojecol an ointment containing zinc oxide and cod liver oil on
      wound healing were compared with ointments that either contained no active
      ingredients or zinc oxide or cod liver oil alone. All formulations enhanced the
      epidermal proliferation after mechanical irritation of the tail skin. The
      combination of zinc oxide and cod liver oil was found to be superior to the
      vehicle control and formulations containing only one active ingredient. This
      combination was also found to be most efficient in accelerating wound healing
      being retarded by repeated dexamethasone treatment.

PMID- 17009811
TI  - Effect of gender on slaughter and carcass traits in Anatolian water buffalo.
AB  - This study determined the effect of gender on slaughter and carcass traits in
      Anatolian water buffalos reared under free range conditions in Turkey. Sixteen
      four-years-old Anatolian water buffalo were divided into two groups of eight
      males in one group and eight females in the other. The slaughter and carcass
      traits, carcass measurement, amount of worthy meat from each animal and
      phenotypic correlations among some carcass traits were determined. Chilling loss,
      slaughter weight and hot and cold carcass weights were 5.27%, 496.44 kg, 234.60
      kg and 222.16 kg, respectively in males and 5.43%, 515.34 kg, 236.08 kg and
      223.00 kg, respectively for females (P > 0.05). The ratio of skin and four leg
      weights (P < 0.05) and skin, head and the legs weights to the live-weight (P <
      0.01) were found significantly higher in males than in female buffalos. In
      addition, from worthy meat, short loin was higher in males compared to females (P
      < 0.05). In this study, it is concluded that, generally carcass yield and amount
      of worthy meat in carcass tends to be higher in male water buffalo compared to
      females.

PMID- 17009810
TI  - [Plasma concentrations of folic acid, vitamin B12 and progesterone of cyclic
      bitches, bitches during pregnancy and induced abortion and bitches with
      pyometra].
AB  - The aim of this study was to investigate the plasma concentrations of folic acid,
      vitamin B12 and progesterone at different stages of the sexual cycle and
      pregnancy, during induced abortion and in bitches with pyometra. Bitches (n = 97)
      were assigned to groups as follows: a) oestrous cycle (n = 42) b) pregnancy (n =
      25) c) induction of abortion (n = 10 and d) pyometra (n = 20). Oestrous cycle
      stages were determined by vaginal inspection and cytology. Pregnancies were
      estimated by ultrasound (5.0 Mhz; linear transducer; Schimadzu) at days 15-25, 35
      45 and 46-63 of pregnancy. Treatments for the induction of abortion were started
      between days 25 and 35 after mating (5 microg/kg cabergoline daily, Galastop; 5
      10 microg/kg Alfaprostol every other day, Gabbrostim). Diagnosis of pyometra was
      confirmed by ultrasound and vaginoscopy. Folic acid and vitamin B12
      concentrations did not differ among different stages of the oestrous cycle. The
      mean concentration of folic acid during early pregnancy (days 15-25) exceeded
      levels of later stages (days 46-63): 9.4 +/- 3.7 microg/ml and 4.7 +/- 1.8
      microg/ml, respectively (p < 0.01). A positive correlation between folic acid and
      vitamin B12 was determined in pregnant dogs ( r = 0.925; p < 0.02). Before the
      induction of abortion, the concentration of folic acid was 9.6 +/- 5.2 microg/ml;
      during abortion it decreased to 5.0 +/- 3.2 microg/ml (p < 0.01). A significant
      correlation (r = 0.925; p < 0.02) between progesterone and folic acid was
      obtained in bitches with abortion. The mean concentration of folic acid in
      bitches with pyometra significantly differed from that of bitches at different
      stages of the oestrous cycle (p < 0.05). The mean concentration of folic acid was
      significantly lower in metoestrous bitches when compared to bitches with pyometra
      (p < 0.05). The decrease of serum concentrations of folic acid during pregnancy
      and induced abortion show that fetal growth and abortion caused higher
      consumption of folic acid. Concerning bitches did not show any deficiency
      symptoms, which is why it can be concluded that this decrease is physiological.

PMID- 17009812
TI  - Occurrence of ovine herpesvirus type-2 infection in sheep and cattle in Samsun
      Province, Turkey.
AB  - July 2004, a cow with clinical signs of ovine herpesvirus type-2 infection which
      is known as sheep associated malignant catarrhal fever (SA-MCF) was reported in
      Samsun Province in Turkey. Blood samples were collected from the suspected cow,
      10 sheep housed with it, and from 150 healthy sheep and 29 healthy cattle
      randomly selected from different places in Samsun Province. Nested polymerase
      chain reaction (n-PCR) was used to detect ovine herpesvirus type-2 (OvHV-2) DNA
      in the suspected cow and competitive- ELISA (c-ELISA) kits were used to detect
      antibodies against OvHV-2. The suspected cow was found to be n-PCR positive and c
      ELISA negative. The serological results were as follows: All 10 (100%) of sheep
      housed with the suspected cow and 18 of 29 (62%) of the randomly selected cattle
      were found seropositive. All 150 randomly selected healthy sheep were
      seronegative. The overall percentage of seropositivity was 14.7% (28/190). OvHV-2
      DNA was detected in the peripheral blood leucocyte (PBL) samples of the cow and
      of the 10 sheep housed with the suspected cow.

PMID- 17009813
TI  - Ichthyosis in two Chianina calves.
AB  - The occurrence of ichthyosis in two Italian Chianina calves is described for the
      first time. Both animals, affected by ichthyosis fetalis and ichthyosis
      congenita, respectively, showed diffuse cutaneous thickening which had been
      present since birth. The first patient was a three-month-old female calf;
      inelastic leather cuirass-like skin associated with generalized hypotrichosis and
      local alopecia, delay of the physiologic change of coat colour, stiff movement
      and growth retardation were the most prominent clinical characteristics. The
      patient was kept under observation for almost one year. The second case occurred
      in a 18-day-old female calf which was referred to our clinic after it had already
      died; the presence of irregular hyperkeratotic plates separated by deep fissures
      over the entire cutaneous surface and the slight eversion of the mucocutaneous
      junction (eclabium and ectropion) were the most characteristic alterations. In
      both cases, the major histopathological feature was a diffuse lamellar
      orthokeratotic hyperkeratosis. An underlying genetic defect was strongly
      suspected on the basis of a common ancestor for the two sires of the affected
      calves and of the current scientific knowledge.

PMID- 17009814
TI  - [Aphakia in a German Holstein calf].
AB  - Aphakia and further malformations of both eyes were diagnosed in a female German
      Holstein calf. Besides aphakia of the left eye, the calf exhibited
      microphthalmia, glaucoma and a hypoplastic uveoscleral tissue. Additional
      findings in the right eye were buphthalmus and glaucoma. Instead of aphakia,
      pathohistological and investigations revealed a very small (microphakia) and
      luxated lens. Neither the clinical nor the pathological examination revealed
      further malformations of other organs. A BVD infection could be excluded as cause
      for the ocular malformations observed. A deficiency or excess of vitamine A was
      unlikely because this would have also applied to all other calves born at the
      same time on the farm. An inbreeding coefficient of 3.168% for the malformed calf
      and the exclusion of environmental causes for these malformations of the eyes let
      us suppose a hereditary problem.

PMID- 17009815
TI  - The distal radioulnar joint in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) involves the wrist in up to 80% of cases; up to 95% of
      patients have signs of wrist arthritis after 12 years of disease. The distal
      radioulnar joint (DRUJ) is involved in 31% to 75% of these patients and is often
      the first compartment of the wrist involved. The inflammatory sequence of events
      leads to the "caput ulnae syndrome" described by Backdahl in 1963. Extensor
      tendon ruptures are frequently associated. The presence of the "scallop" sign on
      radiographs is an alerting sign for tendon attrition. The gold standard in
      treatment remains resection of the distal ulnar head, known as Darrach's
      procedure. The most frequent complication is instability of the proximal ulnar
      stump. In order to restore stability or to prevent instability, several
      stabilisation techniques have been reported with free tendon grafts, the extensor
      carpi ulnaris, the flexor carpi ulnaris, the joint capsule and the pronator
      quadratus muscle. There is no evidence that stabilisation of the proximal ulnar
      stump during the initial operation gives better results. Another drawback of
      ulnar head resection is the progression of ulnar translation of the carpus. There
      are however several surveys showing that this ulnar translocation is the
      consequence of the disease rather than the result of the Darrach procedure.
      Several features such as an increased radial slope (> 23 degrees) and/or
      destruction of the ulnar corner of the distal radial epiphysis have been
      mentioned as predictive elements for further ulnar slide of the carpus. The Sauve
      Kapandji procedure is in these cases a useful alternative choice. Another
      advantage of this technique is that it provides a larger surface so that other
      (radial) procedures can be more easily combined (Chamay partial radiocarpal
      fusion, wrist prosthesis).

PMID- 17009816
TI  - Clinical evaluation of a new custom offset shoulder prosthesis for treatment of
      complex fractures of the proximal humerus.
AB  - Primary hemiarthroplasty of the shoulder is an accepted procedure to treat
      complex proximal humeral fractures. The goal of this study was to assess the
      functional outcome in patients treated with hemiarthroplasty using a custom
      offset shoulder prosthesis, either for an acute four-part fracture of the
      proximal humerus or following failed primary treatment of a complex humeral
      fracture. Thirty seven patients were followed up for a mean of 17 months after
      shoulder replacement (Group A: four-part-fractures; n = 26, Group B:
      posttraumatic necrosis/non-union after failed primary treatment; n = 11). The
      Constant-Murley-Score and radiological score according to Neer's classification
      were used for postoperative functional and radiological assessment. Following
      hemiarthroplasty, Group A achieved an average Constant Score of 52 and Group B of
      46. The pain relief after hemiarthroplasty was about 53% in Group A and only 33%
      in Group B. The least satisfying partial function was shoulder mobility in both
      groups. Radiographic evaluation did not correlate with the Constant Score.
      Patients secondarily treated with arthroplasty seem to have less chance to
      achieve a satisfying functional outcome compared to those with immediate
      hemiarthroplasty. These results emphasise the importance of a careful initial
      decision to select the most appropriate treatment modality in complex fractures
      of the proximal humerus.

PMID- 17009817
TI  - Posteromedial approach to the distal humerus for fracture fixation.
AB  - The authors report their experience with the posteromedial surgical approach of
      the humeral shaft for internal fixation of fractures by plating. Sixteen patients
      were treated for humeral shaft fractures (14 for recent fractures and two for
      nonunion) below the mid-diaphysis, all without injury of the radial nerve.
      Patients were operated in the prone position. Plate and screw fixation on the
      medial side was used in all cases. Fourteen fractures healed without delay, and
      two after revision with bone grafting. There were no surgical complications. The
      posteromedial approach allows the surgeon to avoid dissection of the radial
      nerve, and is an interesting alternative to lateral approaches especially in
      cases of re-operation or nonunion. Preoperative lesion of the radial nerve is
      however a relative contraindication to selecting this posteromedial approach, as
      it does not give access to the radial nerve.

PMID- 17009818
TI  - Complications following resection of the olecranon bursa.
AB  - We retrospectively reviewed 37 cases of resection of the olecranon bursa and
      noted wound healing problems in 10 (27%) and recurrence in 8 (22%). A lateral arm
      flap was necessary in one patient. Conservative treatment remains the treatment
      of choice for olecranon bursitis. Differentiation between septic and non-septic
      cases is challenging. The risk of wound healing problems and recurrence should be
      taken into account when planning surgical resection.

PMID- 17009819
TI  - Development of a clinical decision tool for suspected scaphoid fractures.
AB  - Scaphoid fractures are the most common carpal fractures; their overall incidence
      is however low. Missing a scaphoid fracture may lead to a non-union with a
      possible disastrous outcome for the patient; for this reason, treatment of a
      suspected scaphoid fracture, even without a proven fracture on the first
      radiograph, has been conservative with plaster treatment. There are many clinical
      tests developed to diagnose a scaphoid fracture. However not all tests are
      equally practical, and their sensitivity and specificity are not always known, or
      are very low. In this study 18 clinical tests were evaluated and a subset of 7
      tests remained, which were found to be practical and/or had a high enough
      sensitivity. A clinical decision protocol was developed using a combination of
      these seven tests, in order to improve diagnostic accuracy and at the same time
      reduce unnecessary plaster cast treatment of patients with a suspected scaphoid,
      who turn out to only have a sprained wrist.

PMID- 17009820
TI  - Pilot study evaluating a clinical decision tool on suspected scaphoid fractures.
AB  - In an earlier study we have proposed a scaphoid decision-protocol in order to
      improve diagnostic accuracy in case of suspected scaphoid fractures. This pilot
      study evaluated this protocol. In this pilot study (n = 31) most cases with
      clinical suspicion of scaphoid fractures reached a positive test result on the
      combined 7 clinical tests (93.5%). Using this test combination, no scaphoid
      fractures were missed (no false-negatives; sensitivity 100%), but it also
      included many patients with no scaphoid fracture. Many of these, however, were
      found to have another fracture. In total, 48% had a scaphoid fracture, 19%
      another fracture and 32% no fracture. In the pilot study the proposed protocol
      seems to be a safe protocol, without missing scaphoid fractures. It leads to a
      reduction of unnecessary plaster casting of sprained wrists and produces a marked
      reduction in plain radiographic examinations.

PMID- 17009821
TI  - Safety of carpal tunnel release with a short incision. A cadaver study.
AB  - The standard long incision technique for carpal tunnel release causes inevitable
      damage to skin sensation, the inter-thenar plexus and especially the distal
      branches of the palmar cutaneous branch of the median nerve (PCM), and may cause
      long-term disabling pain and scar tenderness. There are many variations in the
      distal branches of the median nerve at the wrist. Anatomic studies of this region
      also have important clinical implications to prevent injury to important anatomic
      structures. The purpose of this study was to evaluate the short-incision carpal
      tunnel release in cadavers. Several important anatomic structures, with possible
      anatomic variations, pass through the carpal tunnel, and blind percutaneous
      transection of the transverse ligament seems to be a high risk procedure. Sixty
      hands from 40 fresh cadavers were evaluated. Both the transverse ligament and the
      distal third of the deep forearm fascia were released using a Smillie knife. At
      the end of each procedure, the hand was explored for injury to tendinous and
      neurovascular structures of the wrist. In all cases the release of the carpal
      tunnel and the distal third of the forearm fascia was found to be complete. The
      superficial palmar arterial arch, flexor tendons, ulnar nerve and vessels,
      digital nerves, median nerve and its recurrent accessory branches, the flexor
      tendons, and even the subcutaneous tissue over the transverse ligament were
      damaged in no instance. Guyon's canal was entered in 6 (10%) hands without damage
      to its components. The distal branches from the ulnar side of the palmar
      cutaneous branch of the median nerve (PCM) were injured in 8 (13.6%) hands, an
      injury that is almost unavoidable with the classic open technique.

PMID- 17009822
TI  - Assessment of malnutrition in hip fracture patients: effects on surgical delay,
      hospital stay and mortality.
AB  - The importance of malnutrition in elderly hip fracture patients has long been
      recognised. All patients operated upon for a hip fracture over a five-year period
      were assessed according to two nutritional markers : a) serum albumin levels and
      b) peripheral blood total lymphocyte count. Patients were subdivided into groups
      according to the four possible combinations of these results. Outcomes according
      to four clinical outcome parameters were validated: a) waiting time to operation
      b) length of hospitalisation, c) in-hospital mortality, and d) one-year
      postoperative mortality. Significant differences were found between malnourished
      patients and those with normal laboratory values with regard to surgical delay
      and one year postoperative mortality. Malnourished patients were also more likely
      to be hospitalised longer than a month and to die during their hospital stay, but
      the difference was not significant. The combination of serum albumin level and
      total lymphocyte count can be used as an independent prognostic factor in hip
      fracture patients.

PMID- 17009823
TI  - Mid term results of Furlong LOL uncemented hip hemiarthroplasty for fractures of
      the femoral neck.
AB  - We report the mid-term results of hemiarthroplasty with the Furlong
      hydroxyapatite coated bipolar prosthesis for displaced (Garden type III and IV)
      intracapsular hip fracture in 480 patients operated between 1989 and 2000. Three
      hundred sixty eight (77%) patients were lost to follow-up due to death, dementia
      or movement away from the area. In the patients followed up there was an 8%
      reoperation rate for infection, aseptic loosening, periprosthetic fracture and
      acetabular erosion. One hundred and twelve patients with a mean follow-up of 4
      years (3-14) were studied. Eighty eight percent had no or slight pain, 77% could
      mobilise outdoors and 89% needed either no aid or a single walking stick to
      mobilise. Radiographic assessment revealed a stable implant with visible
      osseointegration in 91%. We conclude that hemiarthroplasty with the
      hydroxyapatite coated bipolar Furlong LOL prosthesis for displaced intracapsular
      fracture of the neck of the femur gives good mid term results in elderly patients
      for return to mobility, use of mobility aids and freedom from pain. It avoids the
      need for cement and provides satisfactory incorporation into the host bone. The
      use of a modular head makes revision to total hip replacement easier.

PMID- 17009824
TI  - Hybrid external fixation in periarticular tibial fractures. Good final outcome in
      56 patients.
AB  - Out of 65 patients with periarticular fractures of the tibia treated by use of
      hybrid external fixation (a combination of indigenously manufactured version of
      ring and AO tubular fixator) from February 1997 to October 2003, 56 cases were
      taken up for this study with a minimum follow-up of 12 months. The injury was due
      to a high-velocity motor vehicle accident in 49 and a fall in 7 patients. Thirty
      five were tibial plateau fractures and 21 were distal tibial plafond fractures.
      Forty eight were compound fractures and eight were closed. They were treated by
      debridement (48 compound) and hybrid external fixator (n = 56). All the patients
      were assessed clinically and radiographically for an average follow-up of 42.5
      months (range: 12 to 67). In tibial plateau fractures (n = 35), the final outcome
      was good to excellent in 30, fair in 2 and poor in 3. In tibial plafond fractures
      (n = 21), results were good to excellent in 16, fair in 3 and poor in 2. We
      recommend the use of hybrid external fixator for periarticular tibial fractures
      occurring due to high-energy trauma. In addition, rates of complications as seen
      with other modalities of fixation are greatly reduced. It facilitates adequate
      care of associated soft tissue injuries.

PMID- 17009825
TI  - The value of pre-operative aspiration in the diagnosis of an infected prosthetic
      knee: a retrospective study and review of literature.
AB  - The purpose of this study was to compare the results of cultures of preoperative
      aspiration samples with those of swabs taken intra-operatively. The records of 70
      revision arthroplasties of the knee from 69 patients, 49 females and 20 males,
      were reviewed. The mean age of the patients at time of revision arthroplasty was
      67 years (range: 34 to 89). Sixty-eight knees from 67 patients were included.
      There were 32 true positives, 17 true negatives, 6 false positives and 13 false
      negatives. This led to a specificity, sensitivity and accuracy of 57%, 84% and
      72%, respectively. Based on these findings, pre-operative aspiration has a
      positive predictive value of 71% and a negative predictive value of 74%. When the
      aspiration sample yields a positive culture, the chances are high that the
      prosthetic knee is infected. When aspiration is negative, infection cannot be
      ruled out. Our study suggests that, in such cases, a coagulase negative
      Staphylococcus (CNS) infection has to be considered.

PMID- 17009826
TI  - Prophylactic external fixation and extensive bone debridement for chronic
      osteomyelitis.
AB  - There is universal agreement that treatment of osteomyelitis should consist of
      debridement, obliteration of dead space, tissue coverage and antibiotic therapy,
      with debridement as the most important factor for therapeutic success. Four
      patients, 27 to 72 years old, with chronic osteomyelitis after a fracture of the
      femur (two), or of the tibia (two), were included in this study. The patients had
      already undergone 5 to 15 (mean: 9) surgical procedures. The same surgical
      technique was used in all of them: sinuses were carefully excised down to the
      bone, and necrotic bone was aggressively resected until normal bleeding was seen.
      A prophylactic circular external fixation frame, built on one proximal and one
      distal ring connected to the bone by thin wires and half pins, was used to
      protect and support the limbs, significantly weakened by radical debridement.
      Bone grafting or distraction osteogenesis was not necessary. All wounds healed
      without complications, and the infection did not recur. The average follow-up
      period was 43 months (range: 38 to 54).

PMID- 17009827
TI  - Surgical treatment of hallux valgus: the Gibson-Piggott technique revisited.
AB  - More than 130 surgical procedures have been described to treat hallux valgus
      deformity. The "spike" first distal metatarsal osteotomy was first described by
      Gibson and Piggott in 1962. Despite having the advantage of using only patient's
      "material", this technique has been abandoned by most orthopaedic surgeons, due
      to fear of complications such as breaking of the bony peg and loosening of
      fixation at the osteotomy site. A group of surgeons at our hospital have
      performed 422 Gibson-Piggott procedures between 1985 and 2005 with consistently
      good results. This fact convinced us to "revisit" the procedure. Thirty seven
      consecutive patients (43 feet) who had surgery between July 2000 and December
      2002 were randomly selected as "sample". A Questionnaire based on the American
      Orthopaedic Foot and Ankle Society (AFOS) Score was used for evaluation. Thirty
      three patients (36 feet), i.e. 89% responded to our survey. Average follow-up
      after surgery was 47 months (between 31 and 63 months). Results showed that 30
      patients (91%) had no or only mild pain, 29 patients (88%) had no or only slight
      limitation in activities of daily living and 31 patients (94%) were able to use
      fashionable or comfortable shoes with no problems. When using numerical
      evaluation, 28 patients (85%) scored 65 or more points (from a total of 95
      points), representing a good postoperative result, comparable with other "modern"
      distal metatarsal osteotomies. In conclusion, the Gibson-Piggott procedure was
      shown to be a valuable technique in the treatment of mild or moderate hallux
      valgus deformity.

PMID- 17009828
TI  - Posterior lumbar interbody fusion (PLIF) with cages and local bone graft in the
      treatment of spinal stenosis.
AB  - Posterior lumbar interbody fusion (PLIF) implants are increasingly being used for
      360 degrees fusion after decompression of lumbar spinal stenosis combined with
      degenerative instability. Both titanium and PEEK (PolyEtherEtherKetone) implants
      are commonly used. Assessing the clinical and radiological results as well as
      typical complications, such as migration of the cages, is important. In addition,
      questions such as which radiological parameters can be used to assess successful
      fusion, and whether the exclusive use of local bone graft is sufficient, are
      frequently debated. We prospectively evaluated 30 patients after PLIF
      instrumentation for degenerative lumbar spinal canal stenosis, over a course of
      42 months. In all cases, titanium cages and local bone graft were used for
      spondylodesis. The follow-up protocol of these 30 cases included standardised
      clinical and radiological evaluation at 3, 6, 12 and 42 months after surgery.
      Overall satisfactory results were achieved. With one exception, a stable result
      was achieved with restoration of the intervertebral space in the anterior column.
      After 42 months of follow-up in most cases, a radiologically visible loss of disc
      space height can be demonstrated. Clinically relevant migration of the cage in
      the dorsal direction was detected in one case. Based on our experience, posterior
      lumbar interbody fusion (PLIF) can be recommended for the treatment of
      monosegmental and bisegmental spinal stenosis, with or without segmental
      instability. Postoperative evaluation is mainly based on clinical parameters
      since the titanium implant affects the diagnostic value of imaging studies and is
      responsible for artefacts. The results observed in our group of patients suggest
      that local autologous bone graft procured from the posterior elements after
      decompression is an adequate material for bone grafting in this procedure.

PMID- 17009829
TI  - The effect of local administration of phenytoin on fracture healing: an
      experimental study.
AB  - The antiepileptic drug phenytoin (Diphenylhydantoin) has been documented to have
      a beneficial effect on wound healing; its effect on fracture healing, however is
      still unclear. In an attempt to evaluate any potential benefits phenytoin may
      have on fracture healing, a prospective study was undertaken combining histology,
      histomorphometry and radiology, in which the effects of locally administered
      phenytoin were analysed. Twenty-four Wistar strain rats of 8-9 months age were
      assigned into two groups of 12 each (matched for age, sex and weight). In the
      study group, phenytoin 20 mg/kg was administered through a 24 gauge needle
      directly on to the fracture site every 72 hours, while in the control group an
      equivalent volume of normal saline was administered at similar intervals. At 28
      days radiographic and histological analysis was done, the scoring for which did
      not show any statistical difference between the control and test animals.
      Histomorphometric analysis of the callus however, showed that the total
      periosteal callus on either side of the central bridging callus was mineralised
      to a greater extent in the phenytoin group animals as compared to the control
      group animals (p = 0.011). After analysing our data, we concluded that phenytoin
      does have an influence in fracture healing, albeit small, which is primarily on
      the hard callus region. The hard callus region is the high oxygen tension region
      and the first region to differentiate. It appears that the effect of phenytoin is
      probably exerted at the early mesenchymal differentiation stage. However our
      preliminary work shows that the effect is small and it is not justifiable at this
      stage to advocate the use of phenytoin clinically to augment fracture healing.

PMID- 17009830
TI  - The reverse shoulder prosthesis (Delta III) in acute shoulder fractures:
      technical considerations with respect to stability.
AB  - The reverse shoulder prosthesis reverses the relationship between the scapular
      and humeral component, resulting in a mechanical advantage as the deltoid muscle
      is able to compensate for the rotator cuff deficiency. Based on this mechanical
      advantage, the reverse shoulder prosthesis has become an accepted alternative for
      the treatment of complex proximal humeral fractures. The purpose of this article
      is to discuss technical considerations related to stability in the use of the
      reverse shoulder prosthesis in acute shoulder fractures, based on clinical
      experience.

PMID- 17009831
TI  - Isolated carpal scaphoid dislocation.
AB  - Isolated carpal scaphoid dislocations are rare. Because of this, treatment
      strategies can be conflicting and vague. The current authors present a case of
      isolated scaphoid dislocation that was treated initially with closed reduction
      and percutaneous pinning. Failure of this index treatment necessitated open
      reduction and internal fixation providing an adequate short-term outcome. Current
      treatment strategies now advocate ligament reconstruction as a first-line
      treatment to restore normal anatomy and preserve function.

PMID- 17009832
TI  - Resection of the distal ulna for tumours and stabilisation of the stump. A case
      report and literature review.
AB  - The distal end of the ulna is an uncommon site for primary bone tumours. We
      report the case of a 23-year-old male, with a giant-cell tumour of the distal end
      of the ulna treated with en-bloc resection and stabilisation of the ulnar stump
      using one half of the extensor carpi ulnaris tendon. The amount of bone removed
      from the distal end of the ulna was 9.0 centimeters long. The functional and
      oncological results were excellent. Stabilisation of the ulnar stump, using one
      half of the extensor carpi ulnaris tendon, has been described by Goldner and
      Hayes in 1979, after resection of a relatively small segment of the distal ulna.
      This is the first report on this technique for stabilisation of the ulnar stump
      after resection of a large distal ulnar segment. A literature review of reported
      cases with a resection of the distal ulna for primary bone tumours is presented.
      The available data are inconclusive as to whether a simple excision is adequate
      or a reconstruction/stabilisation is required.

PMID- 17009833
TI  - Compressive blunt trauma of the abdomen and pelvis associated with abdominal
      aortic rupture.
AB  - Blunt trauma to the abdominal aorta is an uncommon but life-threatening injury.
      Its incidence and mortality are related to road traffic accidents and have
      increased during the last years mainly because of the compulsory use of seat
      belts. A high level of suspicion and medical knowledge is necessary for its
      diagnosis and appropriate management. We present a rare case of abdominal
      compression leading to pelvic fracture and disruption of the aortic wall with a
      fatal result. With this case study and a literature review, we would like to
      stress the importance of recognition, management and follow-up of the blunt
      abdominal injuries associated with pelvic trauma in order to improve the outcome.

PMID- 17009834
TI  - Ankylosis due to heterotopic ossification following primary total knee
      arthroplasty.
AB  - We present a case of ankylosis of the knee after knee arthroplasty due to
      heterotopic ossification in the ligaments. Treatment with resection of the
      collateral ligaments, reconstruction with a hinged implant and radiotherapy was
      successful.

PMID- 17009835
TI  - Acute exertional compartment syndrome of the superficial posterior compartment of
      the leg.
AB  - Acute exertional compartment syndrome of the superficial posterior compartment of
      the leg secondary to minor soft tissue injury is rare. This case series
      highlights the risk of misdiagnosis as deep venous thrombosis, followed by
      inadvertent anticoagulation. The delay in management did fortunately not lead to
      catastrophic consequences. Clinicians must not dismiss the possibility of an
      acute exertional compartment syndrome in the absence of direct trauma or after
      minor closed soft tissue injury.

PMID- 17009836
TI  - Cervical spondylolysis: a case report.
AB  - Cervical spondylolysis is defined as a corticated cleft between the superior and
      inferior articular facets of the articular pillar, the cervical equivalent of the
      pars interarticularis in the lumbar spine. Of primary importance is its
      recognition to avoid confusion with more clinically significant abnormalities
      such as fracture or dislocation. This case report describes bilateral
      spondylolysis and associated dysplasia of C5 in a 31-year-old female. We describe
      the radiographic presentation of this anomaly, stressing the importance of
      computed tomography for correct diagnosis. A review of the literature on this
      interesting abnormality and a complete differential diagnosis are presented.

PMID- 17009837
TI  - Pharmacokinetics of telmisartan in healthy Chinese subjects after oral
      administration of two dosage levels.
AB  - To study the pharmacolkinetics of telmisartan in healthy Chinese male subjects
      after oral administration of two dosage levels, 36 healthy subjects were divided
      into two groups and given a single oral dose of 40 or 80 mg telmisartan (CAS
      144701-48-4, MicardisPlus). A sensitive liquid chromatography-tandem mass
      spectrometry method (LC-MS-MS) was used for the determination of telmisartan in
      plasma. Both, a non-compartmental and compartmental method were used for analysis
      of parameters of kinetics. The main pharmacokinetic parameters of the 40 mg and
      80 mg regimen group were as follows: t(max) (1.76 +/- 1.75) h, (1.56 +/- 1.09) h,
      C(max) (163.2 +/- 128.4) ng/mL, (905.7 +/- 583.4) ng/mL, t1/2 (23.6 +/- 10.8) h,
      (23.0 +/- 6.4) h, AUC(o-t) (1456 +/- 1072) ng x h/mL, (6759 +/- 3754) ng x h/mL,
      AUC(o-infinity (1611 +/- 1180) ng x h/mL, (7588 +/- 4661) ng x h/mL,
      respectively. After dose normalization, there was significant difference for main
      pharmacokinetic parameters C(max) AUC(o-t) and AUC(o-infinity) between two dosage
      level groups. The plasma concentration-time profile of telmisartan was
      characterized by a high degree of inter-individual variability and the
      disposition of telmisartan in healthy Chinese subjects was dose-dependent. The
      pharmacokinetic parameters C(max) and AUC(o-inifinity) of the 80 mg regimen group
      increased to about 5-fold compared to that of the 40 mg regimen group, but there
      was no significant difference for t(max) and t1/2 between the two dose groups.

PMID- 17009838
TI  - Evaluation of the non-inferiority of a fixed combination of thyme fluid- and
      primrose root extract in comparison to a fixed combination of thyme fluid extract
      and primrose root tincture in patients with acute bronchitis. A single-blind,
      randomized, bi-centric clinical trial.
AB  - In a single-blind, randomized, bi-centric, prospective study, the non-inferiority
      of a fixed combination of thyme fluid extract and primrose root fluid extract
      (Bronchicum Elixir S, fluid test medication) was evaluated by comparison to a
      fixed combination of thyme fluid extract and primrose root tincture (Bronchcium
      Tropfen, drops test medication). The patients took either 6 x 5 ml of the fluid
      test medication (fluid group) or 5 x 1 ml of the drops test medication (drops
      group) daily. 189 outpatients (121 women, 68 men) suffering from acute, not
      previously treated bronchitis, lasting for less than 48 h, were randomized and
      treated with either fluid (94 patients: 66 women, 28 men) or drops (95 patients:
      55 women, 40 men) over a time period of 7-9 days. 71 patients were excluded from
      the per-protocol (PP) collective because of violations regarding examination time
      points and/or intake of the study medication. The primary outcome criterion was
      to demonstrate the non-inferiority of the Score (BSS) at the end of the study
      compared to baseline. In the fluid group, the BSS decreased from 11.0 +/- 5.0
      points at baseline to 2.6 +/- 4.6 (76%) at study end compared to a decrease from
      11.0 +/- 4.8 points at baseline to 2.5 +/- 4.2 (77.1%) at study end in the drops
      group (Intention-to-treat (ITT) -analysis). The decrease of the BSS in both
      groups was highly significant (p < or = 10(-3)), but there was no difference
      between the two groups. Differences between the study sites were noticed
      regarding the baseline BSS, which were twice as high at study site 2 compared to
      study site 1 (probably due to the different way the patients were recruited).
      However, a statistically significant intergroup difference was not observed at
      any time point. At the end of the study, 52.1% of the patients of the fluid group
      were symptom free and 53.7% of the patients from the drops group were symptom
      free as compared by the ITT-analysis (secondary outcome criterion). For both
      parameters, the PP-analysis support the non-inferiority of the fluid compared to
      the drops. The global therapeutic efficacy of the fluid as well as of the drops
      was rated as being "very good" or "good" by 80% of the patients and clinical
      investigators. The tolerability was very good in both groups; neither serious
      adverse events nor clinically relevant findings in the safety parameters were
      observed. A total of 10 adverse events occurred, 5 in the fluid group and 5 in
      the drops group. Five of these adverse events (2 in the fluid group and 3 in the
      drops group) were considered to be possibly or probably related to the intake of
      the study medication. Neither serious nor unknown adverse drug reactions were
      observed. One drop-out occurred during the study, because of ineffectiveness of
      the study medication. In the global safety assessment, the tolerability of both
      medications was rated by about 90% of the patients and by clinical investigators
      as "good" or "very good". The study demonstrated that the fixed combination of
      thyme fluid extract and primrose root extract and the combination of thyme fluid
      extract and primrose root tincture were well tolerated and showed comparable
      results regarding their efficacy, e.g. decrease of the bronchitis symptoms
      (primary outcome criterion) and in relief of symptoms (secondary outcome
      criterion). The results of the study confirm the non-inferiority of the fluid, a
      combination of thyme fluid extract and primrose root extract when compared to the
      drops, a combination of thyme fluid extract and primrose root tincture.

PMID- 17009839
TI  - Investigation of the spasmolytic activity of the flavonoid fraction of Achillea
      millefolium s.l. on isolated guinea-pig ilea.
AB  - The spasmolytic activity of a flavonoid fraction of a commercial sample of yarrow
      (Achillea millefolium s.l.), its main flavonoids as well as quercetin and two
      flavonoid metabolites were investigated on isolated terminal guinea-pig ilea. The
      aglycones quercetin, luteolin and apigenin exhibited the highest antispasmodic
      activities with IC50 values of 7.8 micromol/L, 9.8 micromol/L and 12.5
      micromol/L, respectively. Rutin and the flavonoid metabolites homoprotocatechuic
      acid and homovanillic acid showed no significant effects on contractility of the
      terminal ilea. From the results on the spasmolytic activity of the flavonoid
      fraction, the glycosides and the respective aglycones it is concluded that in tea
      prepared from yarrow the concentration of the flavonoids is high enough to exert
      a spasmolytic effect in the gut, which is mainly caused by blockade of the
      calcium inward current, but additionally also by mediator-antagonistic effects.

PMID- 17009840
TI  - Comparative bioavailability of two oral suspensions of naproxen sodium.
AB  - The bioavailability of naproxen sodium (CAS 26159-34-2) after administration of
      two oral suspensions, reference or test (Pactens), was compared in 24 healthy
      subjects. The volunteers received an oral dose of 250 mg (10 ml) in two separate
      sessions under fasting conditions according to a randomized cross-over design and
      blood samples were obtained at selected times for a period of 72 h. Plasma
      samples were analyzed by a high-performance liquid chromatographic method for
      determination of naproxen. Individual plasma concentration against time curves
      were constructed and pharmacokinetic parameters were obtained by non
      compartmental techniques. The parameters obtained (mean +/- S.E.M.) were: C(max)
      43.93 +/- 1.83 and 44.91 +/- 2.15 microg/ml, t(max) 2.38 +/- 0.21 and 1.83 < or =
      0.19 h, AUC(72 h) 721.73 +/- 18.47 and 722.55 +/- 19.07 microg x h/ml for
      reference and test formulations, respectively. Maximal concentration, AUC(72 h)
      and AUC(infinity). were log transformed and compared by analysis of variance and
      ratios; in addition, 90% confidence limits were obtained. As confidence limits
      were included in the 80-125% range and the probability of exceeding these
      intervals was always lower than 0.05, it is concluded that the formulations
      tested are bioequivalent.

PMID- 17009841
TI  - Synthesis of some novel sulfur containing triazolothienopyrimidines and
      biscompounds as possible antitumor and radioprotective agents.
AB  - The syntheses of novel 1,2,4-triazolothienopyrimidine derivatives (4a,b),
      thiourea derivatives (5-8) and biscompounds having a thieno[2,3-d]pyrimidine
      nucleus (13-16) utilizing the 2-isothiocyanato derivatives 2a,b are reported. The
      structures of these compounds were confirmed by microanalysis, IR, 1H-NMR and
      mass spectrometry. Preliminary biological studies of some synthesized compounds
      showed promising antitumor and radioprotective activities.

PMID- 17009842
TI  - New silver polypyridyl complexes: synthesis, characterization and biological
      activity on Leishmania mexicana.
AB  - Leishmania parasites are the causal agents of leishmaniasis that currently
      threatens 350 million people in 88 different countries, in the absence of an
      effective drug. In order to continue the development of transition metal
      complexes with planar ligands that show interactions with DNA and activity
      against Leishmania parasites, the synthesis of the complexes [Ag(dpq)2]NO3 (1)
      and [Ag(dppz)2]NO3 (2), which were obtained by the reaction of silver nitrate
      with dpq and dppz, respectively, in a 1:2 molar ratio is reported. These
      complexes were characterized by elemental analysis and 1H-NMR, IR, and UV-vis
      spectroscopies. The most probable structure for these complexes is tetrahedral,
      with two molecules of ligand coordinated to the silver atom and a nitrate as a
      counter ion. Affinity studies of DNA vs. bovine albumin were carried out, and a
      strong interaction of the complexes with DNA was observed. Bioassays were
      undertaken in vitro on promastigotes of Leishmania (L.) mexicana exposed to the
      silver complexes for 48 h. At 10 micromol/L complex 2 induced a leishmanicidal
      effect (LD23), whilst complex 1 reduced the parasites growth rate by 55% (LD55).
      These findings suggest that biological activity could be associated with the
      interaction of the complexes with the parasitic DNA.

PMID- 17009843
TI  - [Study of the toxicity of povidone-lodine for fibroblast-like cells (BALB-3T3)
      and primary human chondrocytes].
AB  - Povidone-iodine (polyvinyl-pyrrolidone-iodine complex, PVP-iodine, CAS 25655-41
      8) is a commonly used antiseptic because of its broad spectrum of antimicrobial
      effect and its comparatively low allergic risk. It is also used for open joint
      lavage. Animal and organ culture studies provide controversial results about the
      risk of cartilage damage due to povidone-iodine. There is a paucity of in vitro
      study data concerning the effect of povidone-iodine on chondrocyte cultures are
      still missing. The aim of this study was therefore to investigate the effect of
      different concentrations and exposition times of povidone-iodine on cell growth
      and differentiation of human chondrocytes. Using of a vitality test (MTT) and a
      proliferation assay (BrdU) in the fibroblast-like cell line BALB3T3, suitable
      concentrations and incubation times were identified to investigate the influence
      of povidone-iodine on proteoglycan synthesis and DNA synthesis of primary human
      chondrocytes. Concentrations of up to 1% povidone-iodine had no significant
      effect on proteoglycan and DNA synthesis of chondrocytes after incubation for 30
      min. An incubation time of 24 h did not inhibit DNA- and proteoglycan synthesis,
      until a concentration of 0.2% povidone-iodine was used. DNA synthesis rate was
      impaired after 10 min incubation with 0.2% and fully inhibited with 1% povidone
      iodine. BALB3T3 reacted more sensitively than chondrocytes. Vitality and
      proliferation rate were fully inhibited at a concentration of 0.5% after the same
      exposition time. However, cells recovered 24 h after 30 min incubation with 0.5%
      povidone-iodine. After incubation with 5% povidone iodine cells did not recover.
      From the results it can be concluded that low concentrations of povidone-iodine
      (< 1%) and short incubation times (< 30 min) have no damaging influence on
      chondrocytes. Previous studies have reported the antimicrobial effectiveness of
      low concentrations of povidone-iodine on the reduction of tissue damage by
      microorganisms. Data from previus studies and the current findings from this
      investigation support the clinical use of povidone-iodine at low concentrations
      and short incubation times for antiseptic treatment of cartilage tissues.

PMID- 17009844
TI  - Bioequivalence of a novel oral metronidazole formulation.
AB  - The plasma pharmacokinetics of metronidazole (CAS 443-48-1) and its active OH
      metabolite (CAS 4812-40-2) were investigated in 16 healthy volunteers after the
      oral administration of single oral doses of 500 mg metronidazole by means of a
      novel (test, T) and reference formulation (reference, R). The trial was conducted
      according to a randomised, controlled, open, within-subject cross-over design
      with two periods one week apart for wash-out. A single oral dose of 500 mg
      metronidazole by means of the test formulation T (Vagimid Dragees) resulted in a
      geometric mean C(max) of 10649 ng/ mL (CV: 0.21) for metronidazole after a median
      t(max) of 70 min (range: 40 to 120); the geometric mean of the AUC(0-t(z)) and
      AUC(0-infinity) were 107406 (CV: 0.25) and 109056 ng x h/mL (CV: 0.26); the
      arithmetic mean of the half-life (t1/2) and the mean residence time (MRT) were
      7.28 h (CV: 0.12) and 11.62 h (CV: 0.10). For the OH-metabolite, the geometric
      mean C(max) was 1941 ng/mL (CV: 0.22) after a median t(max) of 480 min (range:
      360 to 600) with a geometric mean AUC(0-tz) and AUC(0-infinity) of 48653 (CV:
      0.21) and 52417 ng x h/mL (CV: 0.22), respectively; the arithmetic mean t1/2 and
      MRT were 10.60 h (CV: 0.21) and 21.14 h (CV: 0.13), respectively. The test
      formulation was bioequivalent with the reference formulation for both
      metronidazole (90% CI of the treatment ratio of 1.02 to 1.15 and 1.02 to 1.12 for
      C(max) and AUC) and its metabolite (90% CI of 0.92 to 1.05 and 0.98 to 1.06,
      respectively). The treatments were very well tolerated and there were no limiting
      safety-relevant findings.

PMID- 17009846
TI  - Radiolabeled multimeric cyclic RGD peptides as integrin alphavbeta3 targeted
      radiotracers for tumor imaging.
AB  - Integrin alphavbeta3 plays a significant role in tumor angiogenesis and is a
      receptor for the extracellular matrix proteins with the exposed arginine-glycine
      aspartic (RGD) tripeptide sequence. These include vitronectin, fibronectin,
      fibrinogen, lamin, collagen, Von Willibrand's factor, osteoponin, and adenovirus
      particles. Integrin alphavbeta3 is expressed at low levels on epithelial cells
      and mature endothelial cells, but it is overexpressed on the activated
      endothelial cells of tumor neovasculature and some tumor cells. The highly
      restricted expression of integrin alphavbeta3 during tumor growth, invasion, and
      metastasis presents an interesting molecular target for both early detection and
      treatment of rapidly growing solid tumors. In the past decade, many radiolabeled
      linear and cyclic RGD peptide antagonists have been evaluated as the integrin
      alphavbeta3 targeted radiotracers. Significant progress has been made on their
      use for imaging tumors of different origin by single photon emission computed
      tomography (SPECT) or positron emission tomography (PET) in several tumor-bearing
      animal models. [18F]Galacto-RGD is under clinical investigation as the first
      integrin alphavbeta3 targeted radiotracer for noninvasive visualization of the
      activated integrin alphavbeta3 in cancer patients. This review will focus on the
      radiolabeled multimeric cyclic RGD peptides (dimers and tetramers) useful as
      radiotracers to image the tumor integrin alphavbeta3 expression by SPECT and PET,
      and some fundamental aspects for the development of integrin alphavbeta3 targeted
      radiotracers. These include the choice of radionuclide and bifunctional
      chelators, selection of targeting biomolecules, and factors influencing the
      integrin alphavbeta3 binding affinity and tumor uptake, as well as different
      approaches for modification of radiotracer pharmacokinetics.

PMID- 17009847
TI  - Imaging pulmonary inflammation with positron emission tomography: a biomarker for
      drug development.
AB  - Methods currently used to assess lung and airway inflammation are often poorly
      quantitative, invasive, nonspecific, or insensitive. Positron emission tomography
      (PET) with [18F]fluorodeoxyglucose [18F]FDG), on the other hand, is a
      noninvasive, highly sensitive imaging technique that can be used to quantify
      pulmonary inflammation. [18F]FDG, an analogue of glucose, is taken up by the same
      transporters that take up glucose into the cell; therefore, [18F]FDG uptake
      tracks cellular glucose transport, which is highly correlated to the rate of
      cellular glucose metabolism. Recent studies in animal models of neutrophilic lung
      inflammation, as well as in patients with inflammatory lung disease, indicate
      that increased [18F]FDG uptake by the lungs correlates with the number of
      activated neutrophils recovered from the lungs. Therefore, the in vivo
      measurement of pulmonary glucose metabolism is a measure of neutrophil burden
      within the lungs. We propose that FDG-PET imaging can be used as a measurable
      biomarker in the development of drug therapies targeting lung inflammation.

PMID- 17009848
TI  - Choline phospholipid metabolism in cancer: consequences for molecular
      pharmaceutical interventions.
AB  - Over the past decade, our program has focused on understanding the role of the
      physiological environment, tumor vasculature, and metabolism in several of the
      aggressive phenotypic traits of cancer, such as invasion and metastasis. These
      studies have been performed primarily with magnetic resonance (MR) imaging (MRI)
      and spectroscopy (MRS) on human breast and prostate cancer models. During the
      course of these studies, we observed specific changes in choline phospholipid
      metabolism associated with a more aggressive phenotype. Molecular or
      pharmacologic interventions that reduced this aggressiveness were also consistent
      with a reversal of these alterations. In this contextual review, we have outlined
      the insight we have gained from these studies and have discussed some of the
      enzymes and pathways that may present novel targets for pharmaceutical
      interventions in cancer.

PMID- 17009849
TI  - Noninvasive visualization of in vivo drug delivery of poly(L-glutamic acid) using
      contrast-enhanced MRI.
AB  - Biomedical imaging is valuable for noninvasive investigation of in vivo drug
      delivery with polymer conjugates. It can provide real-time information on
      pharmacokinetics, biodistribution, and drug delivery efficiency of the
      conjugates. Noninvasive visualization of in vivo drug delivery of polymer
      conjugates with contrast-enhanced magnetic resonance imaging (MRI) was studied
      with paramagnetically labeled poly(L-glutamic acid) in an animal tumor model.
      Poly(L-glutamic acid) is a biocompatible and biodegradable drug carrier for
      diagnostics and therapeutics. Poly(L-glutamic acid)-1,6-hexanediamine--(Gd-DO3A)
      conjugates with molecular weights of 87, 50, and 28 kDa and narrow molecular
      weight distributions were prepared and studied in mice bearing MDA-MB-231 human
      breast cancer xenografts. Contrast-enhanced MRI resulted in real-time and three
      dimensional visualization of blood circulation, pharmacokinetics,
      biodistribution, and tumor accumulation of the conjugates, and the size effect on
      these pharmaceutics properties. The conjugate of 28 kDa rapidly cleared from the
      circulation and had a relatively lower tumor accumulation. The conjugates with
      higher molecular weights exhibited a more prolonged blood circulation and higher
      tumor accumulation. The difference between the conjugates of 87 and 50 kDa was
      not significant. Contrast-enhanced MRI is effective for noninvasive real-time
      visualization of in vivo drug delivery of paramagnetically labeled polymer
      conjugates.

PMID- 17009850
TI  - Selectin ligands promote ultrasound contrast agent adhesion under shear flow.
AB  - Contrast-enhanced ultrasound imaging has shown promise in the field of molecular
      imaging. This technique relies upon the adhesion of ultrasound contrast agent
      (UCA) to targeted molecular markers of disease. This is accomplished by coating
      the surface of the contrast agent with a ligand that specifically binds to the
      intended molecular marker. Most UCA particles remain in the blood space, and
      their retention is influenced by the forces imposed by blood flow. For a UCA
      bound to a molecular target on the vascular endothelium, blood flow imposes a
      dislodging force that counteracts retention. Additionally, contrast agent
      adhesion to the molecular marker requires rapid binding kinetics, especially in
      rapid blood flow. The ability of a ligand:target bond complex to mediate fast
      adhesion and withstand dislodging force is necessary for efficient ultrasound
      based molecular imaging. In the current study, we describe a flow-based adhesion
      assay which, combined with a novel automated tracking algorithm, enables quick
      determination of the ability of a targeting ligand to mediate effective contrast
      agent adhesion. This system was used to explore the adhesion of UCA targeted to
      the proinflammatory endothelial protein P-selectin via four targeting ligands,
      which revealed several interesting adhesive behaviors. Contrast agents targeted
      with glycoconjugate ligands modeled on P-selectin glycoprotein ligand 1 exhibited
      primarily unstable or transient adhesion, while UCA targeted with an anti-P
      selectin monoclonal antibody exhibited primarily firm adhesion, although the
      efficiency with which these agents were recruited to the target surface was
      relatively low.

PMID- 17009851
TI  - Enhanced tumor visualization by gamma-scintigraphy with 111In-labeled
      polychelating-polymer-containing immunoliposomes.
AB  - Here, we have prepared long-circulating PEGylated liposomes heavily loaded with
      111In via the liposome-incorporated polylysine-based (PLL-based) polychelating
      amphiphilic polymer (PAP) and additionally modified with the monoclonal antibody
      2C5 (mAb 2C5) possessing the nucleosome-restricted (NS-restricted) specificity
      and capable of specific recognition of a broad variety of live cancer cells via
      the cancer cell surface bound NSs. These liposomes have been tested as a tumor
      specific contrast agent for the gamma-scintigraphic visualization of model tumors
      in mice. The tumor accumulation of mAb 2C5 modified liposomes prepared in this
      study was significantly (3-to-5-fold) higher than in the neighboring muscle
      tissue at all times after administration (6, 24, and 48 h) in mice bearing murine
      Lewis lung carcinoma (LLC) and human HT-29 tumors. The whole body direct gamma
      imaging of LLC tumor bearing mice at different times has demonstrated the
      superior in vivo tumor accumulation of the targeted mAb 2C5 modified PAP
      containing PEGylated liposomes compared to nontargeted liposomal control
      formulations, which resulted in better and faster tumor imaging as shown with LLC
      bearing mice.

PMID- 17009852
TI  - Radiopaque alginate microcapsules for X-ray visualization and immunoprotection of
      cellular therapeutics.
AB  - Alginate-poly-L-lysine-alginate (APA) microcapsules have been explored as
      vehicles for therapeutic drug and cell delivery. The permselectivity of these
      capsules provides a unique means of controlled drug release and immunoisolation
      of encapsulated cells. Immunoisolation is especially attractive as it abrogates
      the need for chronic immunosuppressive therapy and opens up the possibility for
      the delivery of numerous cell sources including xenogeneic grafts. APA
      microcapsules containing cellular therapeutics have proven effective in the short
      term treatment of a wide range of diseases requiring enzyme or endocrine
      replacement therapy, including type I diabetes. If these microcapsules could be
      noninvasively monitored with X-ray imaging modalities (i.e., fluoroscopy, CT, and
      digital subtraction angiography), questions such as the ideal transplantation
      site, the best means of delivery, and the long-term survival of grafts could be
      better addressed. We have developed two novel alginate-based radiopaque
      microcapsule formulations containing either barium sulfate (Ba X-Caps) or bismuth
      sulfate (Bi X-Caps). As compared to conventional, nonradiopaque APA capsules, Ba
      X-Caps and Bi X-Caps containing human cadaveric islets resulted in a decrease in
      cellular viability of less than 5% up to 14 days after encapsulation. Both
      radiopaque capsules were found to be permeable to lectins < or =75 kDa, but were
      impermeable to lectins > or =120 kDa, thus ensuring the blockage of the
      penetration of antibodies while allowing free diffusion of insulin and nutrients.
      The glucose-responsive insulin secretion of the radiopaque encapsulated human
      islets was found to be unaltered compared to that of unlabeled controls, with
      human C-peptide levels ranging from 3.21 to 2.87 (Ba X-Caps) and 3.23 to 2.87 (Bi
      X-Caps) ng/islet at 7 and 14 days postencapsulation, respectively. Using
      fluoroscopy, both Ba X-Caps and Bi X-Caps could be readily visualized as single
      radiopaque entities in vitro. Furthermore, following transplantation in vivo in
      mice and rabbits, single capsules could be identified with no significant change
      in contrast for at least 2 weeks. This study represents the first attempt at
      making radiopaque microcapsules for X-ray guided delivery and imaging of cellular
      therapeutics. While human cadaveric islets were used as a proof-of-principle,
      these radiopaque capsules may have wide ranging therapeutic applications for a
      variety of cell types.

PMID- 17009853
TI  - Targeting Beta-3 integrin using a linear hexapeptide labeled with a near-infrared
      fluorescent molecular probe.
AB  - Biomolecules containing the RGD peptide sequence are known to bind integrins with
      high affinity. Studies of hexa-and hepta-peptides labeled with a near-infrared
      fluorescent probe (cypate) showed that rearranging the glycine in a linear RGD
      peptide sequence to form the GRD analogue favored the uptake of the GRD compound
      by alphavbeta3 integrin receptor (ABIR)-positive A549 tumor cells and tissue. The
      internalization of the GRD compound in A549 cells and tumor uptake in mice were
      inhibited by ABIR-avid peptides, suggesting its recognition by this receptor.
      Further studies with functional blocking antibodies and beta3 knockout cells
      revealed that beta3 integrin mediates the internalization of the cypate-GRD
      peptide. Molecular modeling studies supported preferential interaction of the
      probe with the beta3 subunit of integrins relative to the alphav subunit. The
      results demonstrate that the cypate-GRD peptide targets beta3 integrin, thereby
      providing a strategy to monitor drug delivery and efficacy, and physiopathologic
      processes mediated by this protein.

PMID- 17009854
TI  - Macrophage targeted N-(2-hydroxypropyl)methacrylamide conjugates for magnetic
      resonance imaging.
AB  - This study describes the synthesis, characterization and in vitro evaluation of
      targetable N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-gadolinium (Gd)
      chelates for enhanced magnetic resonance imaging (MRI) of macrophages. Copolymers
      of HPMA, methacryloylglycylglycyl-mannosamine (MA-GG-ManN),
      aminopropylmethacrylamide-benzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (APMA-DOTA), and 5-(3-(methacryloylaminopropyl)thioureidyl)
      fluorescein (MA-AP-FITC) were synthesized and characterized. Gd was chelated to
      the polymeric precursors. The conjugates were characterized for gadolinium
      content by inductively coupled plasma optical emission spectrometry (ICP-OES) and
      T1 relaxivity (r1) at room temperature and 1.5 T. The effect of ManN content on
      mannose receptor mediated uptake of THP-1 human macrophages was evaluated as a
      function of time and temperature. The polymer conjugates showed relaxivities in
      the range of 21.8-24.9 s(-1) mM(-1) Gd. Relaxivities of the conjugates per mM Gd
      were up to 7 times higher than that of a commercially available MR contrast agent
      Gd-DOTA. Significantly (p < 0.042) higher uptake was observed for targeted
      conjugates compared to nontargeted conjugates. The uptake of polymeric conjugates
      was time and concentration dependent and appears to be mannose receptor mediated.
      The increased relaxivity coupled with the ability to target these carriers to
      cells containing ManN receptors shows promise for the application of these agents
      in clinical MR imaging of macrophage mediated malignancies.

PMID- 17009855
TI  - Contrast-enhanced magnetic resonance angiography with biodegradable (Gd-DTPA)
      cystamine copolymers: comparison with MS-325 in a swine model.
AB  - The purpose of this study is to evaluate the use of (Gd-DTPA)-cystamine
      copolymers (GDCC), a novel biodegradable intravascular polydisulfide-based
      macromolecular gadolinium(III) contrast agent, for first-pass and steady-state
      contrast-enhanced magnetic resonance angiography (MRA) in a swine model. A breath
      hold background-suppressed 3D MRA of the thorax was performed for first-pass
      imaging and repeated every 10 min after GDCC injection to monitor the tissue
      enhancement time course. A navigator-gated 3D MRA of the coronary arteries was
      performed during steady state following the first-pass imaging. Imaging with
      intravascular agent MS-325 approximately 1 h after GDCC injection was also
      included for comparison. Experimental results indicated that GDCC provided
      significant blood signal-to-noise ratio (SNR) improvement, approximately 1633%
      for first-pass and 33% for steady-state contrast-enhanced MRA. Compared to MS
      325, GDCC provided similar blood enhancement for first-pass and steady-state
      imaging but with a different tissue enhancement time course. The blood SNR
      enhancement half-time was 10 +/- 6 min for GDCC and 46 +/- 33 min for MS-325.
      GDCC provided less enhancement in the liver, bone growth plates, and muscle than
      MS-325.

PMID- 17009856
TI  - A pharmacoproteomics study of the cancer cell line EKVX using capillary-LC/MS/MS.
AB  - The chemotherapeutic agent camptothecin, 10-OH (CPT,10-OH), was shown to act
      synergistically with the epithelial growth factor receptor (EGFR) inhibitor
      (AG1478) against several transformed cell lines. To study the cellular response
      to these drugs, the non-small-cell lung carcinoma cell line, EKVX, was treated
      with these compounds either alone or in combination. We performed a proteomic
      analysis using capillary-HPLC coupled with electrospray ion trap mass
      spectrometry (capillary-LC-ESI/MS) of a tryptic digest to obtain a global protein
      profile of the EKVX cell line and identify changes in protein expression. The
      combination of AG1478 and CPT,10-OH showed synergistic cytotoxicity and also
      changed the expression of multiple proteins, while individual treatments showed a
      lesser effect on protein expression. Thus, the synergistic action of AG1478 and
      CPT,10-OH was reflected in altered protein profiles, showing that a proteomic
      analysis can serve to evaluate chemotherapeutic agents and their combinations.

PMID- 17009857
TI  - Targeted delivery of antisense oligodeoxynucleotide and small interference RNA
      into lung cancer cells.
AB  - Selective gene inhibition by antisense oligodeoxynucleotide (AS-ODN) or by small
      interference RNA (siRNA) therapeutics promises the treatment of diseases that
      cannot be cured by conventional drugs. However, antisense therapy is hindered due
      to poor stability in physiological fluids and limited intracellular uptake. To
      address these problems, a ligand targeted and sterically stabilized nanoparticle
      formulation has been developed in our lab. Human lung cancer cells often
      overexpress the sigma receptor and, thus, can be targeted with a specific ligand
      such as anisamide. AS-ODN or siRNA against human survivin was mixed with a
      carrier DNA, calf thymus DNA, before complexing with protamine, a highly
      positively charged peptide. The resulting particles were coated with cationic
      liposomes consisting of DOTAP and cholesterol (1:1, molar ratio) to obtain LPD
      (liposome-polycation-DNA) nanoparticles. Ligand targeting and steric
      stabilization were then introduced by incubating preformed LPD nanoparticles with
      DSPE-PEG-anisamide, a PEGylated ligand lipid developed earlier in our lab, by the
      postinsertion method. Nontargeted nanoparticles coated with DSPE-PEG were also
      prepared as a control. Antisense activities of nanoparticles were determined by
      survivin mRNA down-regulation, survivin protein down-regulation, ability to
      trigger apoptosis in tumor cells, tumor cell growth inhibition, and
      chemosensitization of the treated tumor cells to anticancer drugs. We found that
      tumor cell delivery and antisense activity of PEGylated nanoparticles were
      sequence dependent and rely on the presence of anisamide ligand. The uptake of
      oligonucleotide in targeted, PEGylated nanoparticles could be competed by excess
      free ligand. Our results suggest that the ligand targeted and sterically
      stabilized nanoparticles can provide a selective delivery of AS-ODN and siRNA
      into lung cancer cells for therapy.

PMID- 17009858
TI  - Molecular dynamics simulations and experimental studies of binding and mobility
      of 7-tert-butyldimethylsilyl-10-hydroxycamptothecin and its 20(S)-4-aminobutyrate
      ester in DMPC membranes.
AB  - The enhanced permeability and retention of liposomes in solid tumors makes
      liposomal formulations attractive for the targeting of various antitumor agents.
      This study explores the binding, orientation, and dynamic properties of a potent
      topoisomerase I inhibitor, 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB
      67), and its 20(S)-4-aminobutyrate ester prodrug (DB-67-AB) in DMPC liposomes by
      molecular dynamics (MD) simulations and experimental studies. MD simulations of
      an all-atom and fully hydrated liquid-crystalline bilayer (2 x 36 DMPC lipids)
      containing single molecules of DB-67 and DB-67-AB were conducted for up to 50 ns.
      Membrane/water partition coefficients for DB-67 and DB-67-AB vs pH were
      determined by ultracentrifugation. Fluorescence spectra and/or steady-state
      anisotropies were measured in various solvents and in DMPC liposomes. Kinetics
      for the reversible DB-67 lactone ring-opening in the presence and absence of DMPC
      liposomes were determined by HPLC with fluorescence detection. During the entire
      simulation time both DB-67 and DB-67-AB were located on the bilayer membrane near
      the polar ester groups of DMPC. The average depth of penetration for DB-67 and DB
      67-AB was similar (12.4-13.2 A) with the prodrug's protonated amino group
      strongly solvated by surface water and lipid phosphate groups. Binding and
      fluorescence experiments revealed only a modest reduction in the binding affinity
      upon attachment of the ionized 4-aminobutyrate group onto DB-67. The binding
      microenvironment polarity resembles that of a polar solvent such as EtOH and
      DMSO. Kinetics experiments confirmed that DB-67 lactone hydrolysis is inhibited
      in the presence of DMPC liposomes, consistent with the reduced exposure of its
      lactone ring to water, as observed in the simulations. Both bound DB-67 and bound
      DB-67-AB have nonrandom orientations and reduced mobility in the membrane,
      especially for diffusion normal to the bilayer surface, and rotational
      relaxation, both of which are > or =2 orders of magnitude slower than in bulk
      water. MD simulations correctly predicted the high binding affinities for DB-67
      AB to DMPC bilayers, protection of bound DB-67 toward lactone hydrolysis, and the
      lack of a substantial reduction in binding for the 20(S)-4-aminobutyrate prodrug
      of DB-67.

PMID- 17009859
TI  - Kinetic and efficacy analysis of RNA interference in stably and transiently
      expressing cell lines.
AB  - RNA interference, particularly through the use of small interfering RNA (siRNA),
      has become an important laboratory tool for both fundamental and applied
      investigations. However, it is currently unknown whether siRNA-mediated knockdown
      of transiently expressed proteins is an acceptable quantitative surrogate for
      stably expressed proteins. Further, the best means by which to transfect cells
      with functionally active siRNA are poorly defined, and determination of the best
      reagent and transfection conditions for a particular cell line is a burdensome
      prerequisite for RNA interference studies. We therefore established the optimal
      transfection conditions for six commercial siRNA delivery reagents in three cell
      lines (HR5-CL11, HeLa, and NIH/3T3) transiently or stably expressing the firefly
      luciferase gene. The delivery efficiency, knockdown kinetics, and cytotoxicity of
      the reagents were evaluated. siPORT Amine, X-tremeGENE, and TransIT-siQUEST
      achieved the best knockdown and consistency of performance among the three cell
      lines. Delivery efficiency varied and was cell line dependent in some cases. The
      knockdown kinetics were reagent-dependent, and knockdown was generally more rapid
      in the stably transfected cells. Cytotoxicity of the reagents was variable.
      GeneSilencer was the least cytotoxic reagent for all three cell lines, and
      TransIT-siQUEST was the most cytotoxic to the HeLa and HR5-CL11 cell lines. These
      comparative results provide an initial basis for reagent selection and
      experimental design for RNA interference studies in HeLa, NIH/3T3, and their
      respective derivative cell lines.

PMID- 17009860
TI  - Cationic poly-L-lysine dendrimers: pharmacokinetics, biodistribution, and
      evidence for metabolism and bioresorption after intravenous administration to
      rats.
AB  - Cationic poly-L-lysine 3H-dendrimers with either 16 or 32 surface amine groups
      (BHALys [Lys]4 [3H-Lys]8 [NH2]16 and BHALys [Lys]8 [3H-Lys]16 [NH2]32, generation
      3 and 4, respectively) have been synthesized and their pharmacokinetics and
      biodistribution investigated after intravenous administration to rats. The
      species in plasma with which radiolabel was associated was also investigated by
      size exclusion chromatography (SEC). Rapid initial removal of radiolabel from
      plasma was evident for both dendrimers (t(1/2) < 5 min). Approximately 1 h
      postdose, however, radiolabel reappeared in plasma in the form of free lysine and
      larger (but nondendrimer) species that coeluted with albumin by SEC. Plasma and
      whole blood pharmacokinetics were similar, precluding interaction with blood
      components as a causative factor in either the rapid removal or reappearance of
      radioactivity in plasma. Administration of monomeric 3H L-lysine also resulted in
      the appearance in plasma of a radiolabeled macromolecular species that coeluted
      with albumin by SEC, suggesting that biodegradation of the dendrimer to L-lysine
      and subsequent bioresorption may explain the pharmacokinetic profiles. Capping
      the Lys8 dendrimer with D-lysine to form BHALys [Lys]4 [3H-Lys]8 [D-Lys]16
      [NH2]32 resulted in similar, and very rapid, initial disappearance kinetics from
      plasma when compared to the L-lysine capped dendrimer. Since significant
      extravasation of these large hydrophilic molecules seems unlikely, this most
      likely reflects both elimination and extensive binding to vascular surfaces.
      Capping with "non-natural" D-lysine also appeared to render the dendrimer
      essentially inert to the biodegradation process. For the L-lysine capped
      dendrimers, radiolabel was widely distributed throughout the major organs, with
      no apparent selectivity for organs of the reticuloendothelial system. In
      contrast, a greater proportion of the administered radiolabel was recovered in
      the organs of the reticuloendothelial system for the D-lysine capped system, as
      might be expected for a nondegrading circulating foreign colloid. To our
      knowledge this is the first data to demonstrate the biodegradation/bioresorption
      of poly-L-lysine dendrimers and has significant implications for the utility of
      these systems as drugs or drug delivery systems.

PMID- 17009861
TI  - Ten simple rules for reviewers.

PMID- 17009862
TI  - The many faces of protein-protein interactions: A compendium of interface
      geometry.
AB  - A systematic classification of protein-protein interfaces is a valuable resource
      for understanding the principles of molecular recognition and for modelling
      protein complexes. Here, we present a classification of domain interfaces
      according to their geometry. Our new algorithm uses a hybrid approach of both
      sequential and structural features. The accuracy is evaluated on a hand-curated
      dataset of 416 interfaces. Our hybrid procedure achieves 83% precision and 95%
      recall, which improves the earlier sequence-based method by 5% on both terms. We
      classify virtually all domain interfaces of known structure, which results in
      nearly 6,000 distinct types of interfaces. In 40% of the cases, the interacting
      domain families associate in multiple orientations, suggesting that all the
      possible binding orientations need to be explored for modelling multidomain
      proteins and protein complexes. In general, hub proteins are shown to use
      distinct surface regions (multiple faces) for interactions with different
      partners. Our classification provides a convenient framework to query genuine
      gene fusion, which conserves binding orientation in both fused and separate
      forms. The result suggests that the binding orientations are not conserved in at
      least one-third of the gene fusion cases detected by a conventional sequence
      similarity search. We show that any evolutionary analysis on interfaces can be
      skewed by multiple binding orientations and multiple interaction partners. The
      taxonomic distribution of interface types suggests that ancient interfaces common
      to the three major kingdoms of life are enriched by symmetric homodimers. The
      classification results are online at http://www.scoppi.org.

PMID- 17009863
TI  - Can transgenic maize affect soil microbial communities?
AB  - The aim of the experiment was to determine if temporal variations of belowground
      activity reflect the influence of the Cry1Ab protein from transgenic maize on
      soil bacteria and, hence, on a regulatory change of the microbial community
      (ability to metabolize sources belonging to different chemical guilds) and/or a
      change in numerical abundance of their cells. Litter placement is known for its
      strong influence on the soil decomposer communities. The effects of the addition
      of crop residues on respiration and catabolic activities of the bacterial
      community were examined in microcosm experiments. Four cultivars of Zea mays L.
      of two different isolines (each one including the conventional crop and its
      Bacillus thuringiensis cultivar) and one control of bulk soil were included in
      the experimental design. The growth models suggest a dichotomy between soils
      amended with either conventional or transgenic maize residues. The Cry1Ab protein
      appeared to influence the composition of the microbial community. The highly
      enhanced soil respiration observed during the first 72 h after the addition of Bt
      maize residues can be interpreted as being related to the presence of the
      transgenic crop residues. This result was confirmed by agar plate counting, as
      the averages of the colony-forming units of soils in conventional treatments were
      about one-third of those treated with transgenic straw. Furthermore, the addition
      of Bt-maize appeared to induce increased microbial consumption of carbohydrates
      in BIOLOG EcoPlates. Three weeks after the addition of maize residues to the
      soils, no differences between the consumption rate of specific chemical guilds by
      bacteria in soils amended with transgenic maize and bacteria in soils amended
      with conventional maize were detectable. Reaped crop residues, comparable to post
      harvest maize straw (a common practice in current agriculture), rapidly influence
      the soil bacterial cells at a functional level. Overall, these data support the
      existence of short Bt-induced ecological shifts in the microbial communities of
      croplands' soils.

PMID- 17009864
TI  - Phylogenetic reconstruction of orthology, paralogy, and conserved synteny for dog
      and human.
AB  - Accurate predictions of orthology and paralogy relationships are necessary to
      infer human molecular function from experiments in model organisms. Previous
      genome-scale approaches to predicting these relationships have been limited by
      their use of protein similarity and their failure to take into account multiple
      splicing events and gene prediction errors. We have developed PhyOP, a new
      phylogenetic orthology prediction pipeline based on synonymous rate estimates,
      which accurately predicts orthology and paralogy relationships for transcripts,
      genes, exons, or genomic segments between closely related genomes. We were able
      to identify orthologue relationships to human genes for 93% of all dog genes from
      Ensembl. Among 1:1 orthologues, the alignments covered a median of 97.4% of
      protein sequences, and 92% of orthologues shared essentially identical gene
      structures. PhyOP accurately recapitulated genomic maps of conserved synteny.
      Benchmarking against predictions from Ensembl and Inparanoid showed that PhyOP is
      more accurate, especially in its predictions of paralogy. Nearly half (46%) of
      PhyOP paralogy predictions are unique. Using PhyOP to investigate orthologues and
      paralogues in the human and dog genomes, we found that the human assembly
      contains 3-fold more gene duplications than the dog. Species-specific duplicate
      genes, or "in-paralogues," are generally shorter and have fewer exons than 1:1
      orthologues, which is consistent with selective constraints and mutation biases
      based on the sizes of duplicated genes. In-paralogues have experienced elevated
      amino acid and synonymous nucleotide substitution rates. Duplicates possess
      similar biological functions for either the dog or human lineages. Having
      accounted for 2,954 likely pseudogenes and gene fragments, and after separating
      346 erroneously merged genes, we estimated that the human genome encodes a
      minimum of 19,700 protein-coding genes, similar to the gene count of nematode
      worms. PhyOP is a fast and robust approach to orthology prediction that will be
      applicable to whole genomes from multiple closely related species. PhyOP will be
      particularly useful in predicting orthology for mammalian genomes that have been
      incompletely sequenced, and for large families of rapidly duplicating genes.

PMID- 17009865
TI  - Targeted molecular dynamics study of C-loop closure and channel gating in
      nicotinic receptors.
AB  - The initial coupling between ligand binding and channel gating in the human
      alpha7 nicotinic acetylcholine receptor (nAChR) has been investigated with
      targeted molecular dynamics (TMD) simulation. During the simulation, eight
      residues at the tip of the C-loop in two alternating subunits were forced to move
      toward a ligand-bound conformation as captured in the crystallographic structure
      of acetylcholine binding protein (AChBP) in complex with carbamoylcholine.
      Comparison of apo- and ligand-bound AChBP structures shows only minor
      rearrangements distal from the ligand-binding site. In contrast, comparison of
      apo and TMD simulation structures of the nAChR reveals significant changes toward
      the bottom of the ligand-binding domain. These structural rearrangements are
      subsequently translated to the pore domain, leading to a partly open channel
      within 4 ns of TMD simulation. Furthermore, we confirmed that two highly
      conserved residue pairs, one located near the ligand-binding pocket (Lys145 and
      Tyr188), and the other located toward the bottom of the ligand-binding domain
      (Arg206 and Glu45), are likely to play important roles in coupling agonist
      binding to channel gating. Overall, our simulations suggest that gating movements
      of the alpha7 receptor may involve relatively small structural changes within the
      ligand-binding domain, implying that the gating transition is energy-efficient
      and can be easily modulated by agonist binding/unbinding.

PMID- 17009866
TI  - "A re-evaluation of M. prototuberculosis": continuing the debate.

PMID- 17009867
TI  - A re-evaluation of M. prototuberculosis.

PMID- 17009868
TI  - Assembly and budding of Ebolavirus.
AB  - Ebolavirus is responsible for highly lethal hemorrhagic fever. Like all viruses,
      it must reproduce its various components and assemble them in cells in order to
      reproduce infectious virions and perpetuate itself. To generate infectious
      Ebolavirus, a viral genome-protein complex called the nucleocapsid (NC) must be
      produced and transported to the cell surface, incorporated into virions, and then
      released from cells. To further our understanding of the Ebolavirus life cycle,
      we expressed the various viral proteins in mammalian cells and examined them
      ultrastructurally and biochemically. Expression of nucleoprotein alone led to the
      formation of helical tubes, which likely serve as a core for the NC. The matrix
      protein VP40 was found to be critical for transport of NCs to the cell surface
      and for the incorporation of NCs into virions, where interaction between
      nucleoprotein and the matrix protein VP40 is likely essential for these
      processes. Examination of virus-infected cells revealed that virions containing
      NCs mainly emerge horizontally from the cell surface, whereas empty virions
      mainly bud vertically, suggesting that horizontal budding is the major mode of
      Ebolavirus budding. These data form a foundation for the identification and
      development of potential antiviral agents to combat the devastating disease
      caused by this virus.

PMID- 17009869
TI  - Release of sequestered malaria parasites upon injection of a glycosaminoglycan.
AB  - Severe human malaria is attributable to an excessive sequestration of Plasmodium
      falciparum-infected and uninfected erythrocytes in vital organs. Strains of P.
      falciparum that form rosettes and employ heparan sulfate as a host receptor are
      associated with development of severe forms of malaria. Heparin, which is similar
      to heparan sulfate in that it is composed of the same building blocks, was
      previously used in the treatment of severe malaria, but it was discontinued due
      to the occurrence of serious side effects such as intracranial bleedings. Here we
      report to have depolymerized heparin by periodate treatment to generate novel
      glycans (dGAG) that lack anticoagulant-activity. The dGAGs disrupt rosettes,
      inhibit merozoite invasion of erythrocytes and endothelial binding of P.
      falciparum-infected erythrocytes in vitro, and reduce sequestration in in vivo
      models of severe malaria. An intravenous injection of dGAGs blocks up to 80% of
      infected erythrocytes from binding in the micro-vasculature of the rat and
      releases already sequestered parasites into circulation. P. falciparum-infected
      human erythrocytes that sequester in the non-human primate Macaca fascicularis
      were similarly found to be released in to the circulation upon a single injection
      of 500 mug of dGAG. We suggest dGAGs to be promising candidates for adjunct
      therapy in severe malaria.

PMID- 17009870
TI  - Trypanin, a component of the flagellar Dynein regulatory complex, is essential in
      bloodstream form African trypanosomes.
AB  - The Trypanosoma brucei flagellum is a multifunctional organelle with critical
      roles in motility, cellular morphogenesis, and cell division. Although motility
      is thought to be important throughout the trypanosome lifecycle, most studies of
      flagellum structure and function have been restricted to the procyclic lifecycle
      stage, and our knowledge of the bloodstream form flagellum is limited. We have
      previously shown that trypanin functions as part of a flagellar dynein regulatory
      system that transmits regulatory signals from the central pair apparatus and
      radial spokes to axonemal dyneins. Here we investigate the requirement for this
      dynein regulatory system in bloodstream form trypanosomes. We demonstrate that
      trypanin is localized to the flagellum of bloodstream form trypanosomes, in a
      pattern identical to that seen in procyclic cells. Surprisingly, trypanin RNA
      interference is lethal in the bloodstream form. These knockdown mutants fail to
      initiate cytokinesis, but undergo multiple rounds of organelle replication,
      accumulating multiple flagella, nuclei, kinetoplasts, mitochondria, and flagellum
      attachment zone structures. These findings suggest that normal flagellar beat is
      essential in bloodstream form trypanosomes and underscore the emerging concept
      that there is a dichotomy between trypanosome lifecycle stages with respect to
      factors that contribute to cell division and cell morphogenesis. This is the
      first time that a defined dynein regulatory complex has been shown to be
      essential in any organism and implicates the dynein regulatory complex and other
      enzymatic regulators of flagellar motility as candidate drug targets for the
      treatment of African sleeping sickness.

PMID- 17009871
TI  - The genetics of axonal transport and axonal transport disorders.
AB  - Neurons are specialized cells with a complex architecture that includes elaborate
      dendritic branches and a long, narrow axon that extends from the cell body to the
      synaptic terminal. The organized transport of essential biological materials
      throughout the neuron is required to support its growth, function, and viability.
      In this review, we focus on insights that have emerged from the genetic analysis
      of long-distance axonal transport between the cell body and the synaptic
      terminal. We also discuss recent genetic evidence that supports the hypothesis
      that disruptions in axonal transport may cause or dramatically contribute to
      neurodegenerative diseases.

PMID- 17009873
TI  - Genomic environment predicts expression patterns on the human inactive X
      chromosome.
AB  - What genomic landmarks render most genes silent while leaving others expressed on
      the inactive X chromosome in mammalian females? To date, signals determining
      expression status of genes on the inactive X remain enigmatic despite the
      availability of complete genomic sequences. Long interspersed repeats (L1s),
      particularly abundant on the X, are hypothesized to spread the inactivation
      signal and are enriched in the vicinity of inactive genes. However, both L1s and
      inactive genes are also more prevalent in ancient evolutionary strata. Did L1s
      accumulate there because of their role in inactivation or simply because they
      spent more time on the rarely recombining X? Here we utilize an experimentally
      derived inactivation profile of the entire human X chromosome to uncover
      sequences important for its inactivation, and to predict expression status of
      individual genes. Focusing on Xp22, where both inactive and active genes reside
      within evolutionarily young strata, we compare neighborhoods of genes with
      different inactivation states to identify enriched oligomers. Occurrences of such
      oligomers are then used as features to train a linear discriminant analysis
      classifier. Remarkably, expression status is correctly predicted for 84% and 91%
      of active and inactive genes, respectively, on the entire X, suggesting that
      oligomers enriched in Xp22 capture most of the genomic signal determining
      inactivation. To our surprise, the majority of oligomers associated with
      inactivated genes fall within L1 elements, even though L1 frequency in Xp22 is
      low. Moreover, these oligomers are enriched in parts of L1 sequences that are
      usually underrepresented in the genome. Thus, our results strongly support the
      role of L1s in X inactivation, yet indicate that a chromatin microenvironment
      composed of multiple genomic sequence elements determines expression status of X
      chromosome genes.

PMID- 17009872
TI  - A look to future directions in gene therapy research for monogenic diseases.
AB  - The concept of gene therapy has long appealed to biomedical researchers and
      clinicians because it promised to treat certain diseases at their origins. In the
      last several years, there have been several trials in which patients have
      benefited from gene therapy protocols. This progress, however, has revealed
      important problems, including the problem of insertional oncogenesis. In this
      review, which focuses on monogenic diseases, we discuss the problem of
      insertional oncogenesis and identify areas for future research, such as
      developing more quantitative assays for risk and efficacy, and ways of minimizing
      the genotoxic effects of gene therapy protocols, which will be important if gene
      therapy is to fulfill its conceptual promise.

PMID- 17009874
TI  - Analysis of pleiotropic transcriptional profiles: a case study of DNA gyrase
      inhibition.
AB  - Genetic and environmental perturbations often result in complex transcriptional
      responses involving multiple genes and regulons. In order to understand the
      nature of a response, one has to account for the contribution of the downstream
      effects to the formation of a response. Such analysis can be carried out within a
      statistical framework in which the individual effects are independently collected
      and then combined within a linear model. Here, we modeled the contribution of DNA
      replication, supercoiling, and repair to the transcriptional response of
      inhibition of the Escherichia coli gyrase. By representing the gyrase inhibition
      as a true pleiotropic phenomenon, we were able to demonstrate that: (1) DNA
      replication is required for the formation of spatial transcriptional domains; (2)
      the transcriptional response to the gyrase inhibition is coordinated between at
      least two modules involved in DNA maintenance, relaxation and damage response;
      (3) the genes whose transcriptional response to the gyrase inhibition does not
      depend on the main relaxation activity of the cell can be classified on the basis
      of a GC excess in their upstream and coding sequences; and (4) relaxation by
      topoisomerase I dominates the transcriptional response, followed by the effects
      of replication and RecA. We functionally tested the effect of the interaction
      between relaxation and repair activities, and found support for the model derived
      from the microarray data. We conclude that modeling compound transcriptional
      profiles as a combination of downstream transcriptional effects allows for a more
      realistic, accurate, and meaningful representation of the transcriptional
      activity of a genome.

PMID- 17009875
TI  - Gene mutations and genomic rearrangements in the mouse as a result of transposon
      mobilization from chromosomal concatemers.
AB  - Previous studies of the Sleeping Beauty (SB) transposon system, as an insertional
      mutagen in the germline of mice, have used reverse genetic approaches. These
      studies have led to its proposed use for regional saturation mutagenesis by
      taking a forward-genetic approach. Thus, we used the SB system to mutate a region
      of mouse Chromosome 11 in a forward-genetic screen for recessive lethal and
      viable phenotypes. This work represents the first reported use of an insertional
      mutagen in a phenotype-driven approach. The phenotype-driven approach was
      successful in both recovering visible and behavioral mutants, including dominant
      limb and recessive behavioral phenotypes, and allowing for the rapid
      identification of candidate gene disruptions. In addition, a high frequency of
      recessive lethal mutations arose as a result of genomic rearrangements near the
      site of transposition, resulting from transposon mobilization. The results
      suggest that the SB system could be used in a forward-genetic approach to recover
      interesting phenotypes, but that local chromosomal rearrangements should be
      anticipated in conjunction with single-copy, local transposon insertions in
      chromosomes. Additionally, these mice may serve as a model for chromosome
      rearrangements caused by transposable elements during the evolution of vertebrate
      genomes.

PMID- 17009878
TI  - Twenty paces from history: an interview with Soraya de Chadarevian by Jane
      Gitschier.

PMID- 17009876
TI  - Evidence for diversity in transcriptional profiles of single hematopoietic stem
      cells.
AB  - Hematopoietic stem cells replenish all the cells of the blood throughout the
      lifetime of an animal. Although thousands of stem cells reside in the bone
      marrow, only a few contribute to blood production at any given time. Nothing is
      known about the differences between individual stem cells that dictate their
      particular state of activation readiness. To examine such differences between
      individual stem cells, we determined the global gene expression profile of 12
      single stem cells using microarrays. We showed that at least half of the genetic
      expression variability between 12 single cells profiled was due to biological
      variation in 44% of the genes analyzed. We also identified specific genes with
      high biological variance that are candidates for influencing the state of
      readiness of individual hematopoietic stem cells, and confirmed the variability
      of a subset of these genes using single-cell real-time PCR. Because apparent
      variation of some genes is likely due to technical factors, we estimated the
      degree of biological versus technical variation for each gene using identical RNA
      samples containing an RNA amount equivalent to that of single cells. This enabled
      us to identify a large cohort of genes with low technical variability whose
      expression can be reliably measured on the arrays at the single-cell level. These
      data have established that gene expression of individual stem cells varies
      widely, despite extremely high phenotypic homogeneity. Some of this variation is
      in key regulators of stem cell activity, which could account for the differential
      responses of particular stem cells to exogenous stimuli. The capacity to
      accurately interrogate individual cells for global gene expression will
      facilitate a systems approach to biological processes at a single-cell level.

PMID- 17009879
TI  - Applied neuropsychology: special issue ethical controversies in neuropsychology.

PMID- 17009877
TI  - Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA.
AB  - The histone variant H2A.Z is evolutionarily conserved and plays an essential role
      in mice, Drosophila, and Tetrahymena. The essential function of H2A.Z is unknown,
      with some studies suggesting a role in transcriptional repression and others in
      activation. Here we show that Caenorhabditis elegans HTZ-1/H2A.Z and the
      remodeling complex MYS-1/ESA1-SSL-1/SWR1 synergize with the FoxA transcription
      factor PHA-4 to coordinate temporal gene expression during foregut development.
      We observe dramatic genetic interactions between pha-4 and htz-1, mys-1, and ssl
      1. A survey of transcription factors reveals that this interaction is specific,
      and thus pha-4 is acutely sensitive to reductions in these three proteins. Using
      a nuclear spot assay to visualize HTZ-1 in living embryos as organogenesis
      proceeds, we show that HTZ-1 is recruited to foregut promoters at the time of
      transcriptional onset, and this recruitment requires PHA-4. Loss of htz-1 by RNAi
      is lethal and leads to delayed expression of a subset of foregut genes. Thus, the
      effects of PHA-4 on temporal regulation can be explained in part by recruitment
      of HTZ-1 to target promoters. We suggest PHA-4 and HTZ-1 coordinate temporal gene
      expression by modulating the chromatin environment.

PMID- 17009880
TI  - Ethical controversies in neuropsychological test selection, administration, and
      interpretation.
AB  - Due to the lack of uniform agreement on certain aspects of neuropsychological
      assessment practice, ethical issues can arise. Ethical controversies related to
      some of the most basic assessment practices of the clinical neuropsychologist are
      addressed. Current controversies related to neuropsychological test selection,
      test administration, and test interpretation are discussed and illustrated by
      case vignettes. Brief analyses of the ethical ramifications of the controversies
      are offered, followed by suggestions and recommendations for dealing with these
      conflicts. By resolving these conflicts as a discipline, more consistent
      standards of neuropsychological practice could be established, which would be of
      ultimate benefit to both professional and consumer alike.

PMID- 17009881
TI  - Ethical issues associated with the assessment of exaggeration, poor effort, and
      malingering.
AB  - The use of effort tests is standard practice in forensic neuropsychology. There
      is a tremendous amount of good information available in test manuals and the
      research literature regarding the proper and responsible use of these tests.
      However, it is clear that there are numerous ethical issues and considerations
      associated with the assessment of exaggeration, poor effort, and malingering.
      Many of these issues are discussed, and recommendations are provided.

PMID- 17009882
TI  - Ethical issues in cross-cultural neuropsychology.
AB  - Clinical neuropsychologists who assess patients from diverse cultural and
      linguistic backgrounds face unique ethical challenges. In this article, we
      address 4 critical questions relevant to ethics of cross-cultural
      neuropsychology: (a) Should culture or race be considered in neuropsychological
      testing? (b) Should race- and ethnicity-specific normative data be used in the
      clinical neuropsychological evaluation? (c) Who is competent to design and
      translate tests for ethnic minority groups and non-English speakers and who is
      competent to administer and interpret them? and (d) Are neuropsychology training
      programs adequately preparing clinicians to be competent in the assessment of
      cross-cultural groups? The overall aims of the article are to highlight the
      complexity of these clinical and ethical issues, to provide comprehensive and
      balanced information to help guide clinician choices, and to stimulate future
      research in this area.

PMID- 17009883
TI  - Evaluation of competency: ethical considerations for neuropsychologists.
AB  - The assessment of decision-making capacity is an essential element of competency
      determinations. As experts in the assessment of human cognitive abilities,
      neuropsychologists may be the best adjudicators of competency. However, to
      maximize the contribution of neuropsychology to the courts in the determination
      of competency, clinicians must be aware of the professional controversies and
      ethical challenges inherent in the assessment of decision-making capacity and the
      determination of competence. Professional controversies include the lack of
      established methodological and procedural guidelines for capacity evaluations and
      the application of variable criteria to establish impairment. Ethical challenges
      include balancing the need to respect the individual's freedom of choice and self
      determination with the need to promote the individual's safety; attaining
      professional competence; and selecting, using, and interpreting assessment
      methods appropriately. The purpose of this article is to examine these issues in
      the context of neuropsychological practice.

PMID- 17009884
TI  - The ethical and clinical practice of disclosing raw test data: addressing the
      ongoing debate.
AB  - Neuropsychologists are prone to having raw test data requested by colleagues,
      clients, and attorneys. Although questions of when and to whom neuropsychologists
      should release raw test data have been debated for years, uncertainty about how
      to address requests for raw test data persists. Although contradictions within
      and between ethical and legal guidelines exist, general bioethical principles,
      most ethical and professional guidelines, and federal copyright law support the
      responsibility of practitioners to maintain the security of neuropsychological
      tests, including raw test data. Neuropsychologists are best served by taking a
      proactive approach regarding the manner in which requests for raw test data are
      addressed. The purpose of this article is to provide the information necessary to
      make informed decisions regarding the release of raw test data; however, each
      neuropsychologist must ultimately choose to pursue a course of action that is
      simply ethically acceptable or one that is ethically preferable.

PMID- 17009885
TI  - Neurocognitive enhancement: ethical considerations for an emerging subspecialty.
AB  - Clinical neuropsychology has traditionally focused on the diagnosis and treatment
      of pathology. However, recent technological advances have begun to make possible
      the enhancement of healthy neurocognitive functioning. The potential to improve
      normal neurocognitive abilities, and the options for providing such improvement,
      raise complex ethical issues. To best serve consumers, the profession, and
      society, neuropsychologists must begin to consider the ethical issues related to
      neurocognitive enhancement. This article reviews neurocognitive enhancement
      methods, introduces and examines ethical issues that emerge when the enhancement
      of healthy neurocognitive functioning is considered, and offers recommendations
      for neuropsychologists entering this emerging subspecialty.

PMID- 17009888
TI  - Nonhuman primates: embryonic stem cells and transgenesis.

PMID- 17009889
TI  - A comparison of reproductive characteristics of boars generated by somatic cell
      nuclear transfer to highly related conventionally produced boars.
AB  - This study compares the reproductive performance of boars produced by somatic
      cell nuclear transfer versus conventional breeding. Two different genotypes were
      selected for comparison: terminal cross line 1 (TX1) and terminal cross line 2
      (TX2). The boars selected for comparison from TX1 were three cloned boars,
      produced by somatic cell nuclear transfer and the conventionally produced
      progenitor of the clones. The boars selected for comparison from TX2 were a
      cloned boar produced by somatic cell nuclear transfer and two conventionally
      produced half sibling boars that were offspring of the progenitor of the clone.
      Semen from each boar was collected, extended, evaluated and shipped offsite. Upon
      arrival, the semen was reevaluated and utilized for artificial insemination of 89
      commercial gilts, at least 12 gilts per boar, producing 625 piglets. Pregnancy
      rates were determined at day 30 and 110 of gestation; and farrowing rate and
      gestation length were recorded. Differences were observed in some of the semen
      characteristics analyzed with the clones usually possessing superior semen
      quality to the control, this likely being a result of age differences amongst the
      clones and controls. Additionally no differences were noted between the clones
      and controls (progenitor) or between individual boars within genetic line for
      pregnancy rates, gestation length or any of the litter parameters examined
      between the clones and controls. These data further support previous reports with
      limited numbers that the reproductive capabilities of cloned boars are equal to
      that of conventionally produced boars.

PMID- 17009890
TI  - Sodium butyrate activates genes of early pancreatic development in embryonic stem
      cells.
AB  - Embryonic stem (ES) cells can differentiate into any tissue, including pancreatic
      islet cell types. Protocols for the efficient generation of these cells in vitro
      could have therapeutic applications for type I diabetes. Here we describe a
      simple method for the differentiation of mouse ES cells into epithelial cells
      with a gene expression profile consistent with that expected of early pancreatic
      progenitors (PP). It is based on the addition of sodium butyrate, an agent known
      to induce chromatin rearrangements. Variations on the length of exposure to
      butyrate result in the generation of hepatocytes or PP-like cells. qRT-PCR
      indicates that butyrate induces mesendoderm/definitive endoderm, but not
      neuroectoderm differentiation. PPlike cells show a strong upregulation of
      Ipf1/Pdx1, p48, Isl-1 and Nkx6.1, but not Ngn3, NeuroD/ Beta2 or Pax4. PP-like
      cells also express the epithelial marker E-cadherin. Taken together, our
      observations suggest that butyrate stimulates early events of pancreatic
      specification, prior to the onset of endocrine differentiation. These findings
      are discussed in the context of the development of protocols for the in vitro
      differentiation of islets.

PMID- 17009891
TI  - Isolation of bovine cardiomyocytes for reprogramming studies based on nuclear
      transfer.
AB  - The goal of this study was to establish and validate a protocol for preparing
      bovine cardiomyocytes from slaughterhouse material for nuclear transfer
      experiments. The cardiomyocyte was selected because it is a terminally
      differentiated cell and strongly expresses a unique subset of genes which can be
      monitored during the reprogramming period. A total of 39 trials were conducted,
      and an optimized protocol was developed yielding individual contractile
      cardiomyocytes from 3-5-month-old bovine fetuses The basic protocol involves
      stabilization of bovine heart tissue for transportation from the slaughterhouse
      to the laboratory by perfusion with Custodiol. This was followed by an enzymatic
      dissociation with collagenase in calcium-free medium and yielded individual
      contractile rod-shaped cardiomyocytes. Subsequent addition of Ca2+ caused the
      cardiomyocytes to round up which was an essential pre-condition for drawing them
      into glass transfer pipettes for delivery into the perivitelline space and for
      efficient electrofusion with cytoplasts derived from in vitro matured bovine
      oocytes. The use of cardiomyocytes maintained at 37 degrees C in nuclear
      transfer, resulted in a significantly reduced proportion of blastocysts compared
      to adult fibroblasts (14.0% versus 32.7%). Storage of cardiomyocytes at 4 degrees
      C prior to nuclear transfer was not compatible with blastocyst development. It is
      expected that this system will be valuable for investigating the reprogramming of
      gene expression which occurs after somatic cell nuclear transfer.

PMID- 17009892
TI  - In vitro development of cloned embryos derived from miniature pig somatic cells
      after activation by ultrasound stimulation.
AB  - The present study was carried out to examine the activation and development of
      cloned embryos produced by transferring miniature pig somatic cells into
      enucleated farm pig oocytes after exposing to ultrasound. The rates of the
      pronucleus-like structure formation and polar body-like structure extrusion in
      embryos exposed to ultrasound did not differ from those applied electric pulses.
      Although there was no significant difference in the blastocyst formation rates
      between different activation methods, the mean number of cells in the blastocysts
      developed from embryos activated by exposing to ultrasound was significantly (p <
      0.05) higher than that obtained by applying electric pulses. The results of the
      present study showed that ultrasound stimulation can induce the activation and in
      vitro development of cloned embryos derived from miniature pig somatic cells.

PMID- 17009893
TI  - Use of adult mesenchymal stem cells isolated from bone marrow and blood for
      somatic cell nuclear transfer in pigs.
AB  - Mesenchymal stem cells (MSCs) isolated from bone marrow were used to examine the
      hypothesis that a less differentiated cell type could increase adult somatic cell
      nuclear transfer (SCNT) efficiencies in the pig. SCNT embryos were produced using
      a fusion before activation protocol described previously and the rate at which
      these developed to the blastocyst stage compared with that using fibroblasts
      obtained from ear tissue from the same animal. The use of bone marrow MSCs did
      not increase cleavage rates compared with adult fibroblasts. However, the
      percentage of embryos that developed to the blastocyst stage was almost doubled,
      providing support for the hypothesis that a less differentiated cell can increase
      cloning efficiencies. As MSCs are relatively difficult to isolate from the bone
      marrow of live animals, a second experiment was undertaken to determine whether
      MSCs could be isolated from the peripheral circulation and used for SCNT. Blood
      MSCs were successfully isolated from four of the five pigs sampled. These cells
      had a similar differentiation capacity and marker profile to those isolated from
      bone marrow but did not result in increased rates of development. This is the
      first study to our knowledge, to report that MSCs can be derived from peripheral
      blood and used for SCNT for any species. These cells can be readily obtained
      under relatively sterile conditions compared with adult fibroblasts and as such,
      may provide an alternative cell type for cloning live animals.

PMID- 17009894
TI  - Nuclear reprogramming of somatic cells by embryonic stem cells is affected by
      cell cycle stage.
AB  - Hybrid embryonic stem (ES)-like clones were generated by fusion of murine ES
      cells with somatic cells that carried a neo resistance gene under the
      transcriptional control of the Oct-4 promoter. The Oct-4 promoter was reactivated
      in hybrid ES cells formed by fusion with fetal fibroblasts, and all hybrid
      colonies were of ES rather than fibroblast phenotype, suggesting efficient
      reprogramming of fibroblast chromosomes. Like normal diploid murine ES cells,
      hybrid lines expressed alkaline phosphatase activity and formed differentiated
      cells derived from the three embryonic germ layers both in vitro and in vivo.
      Treatments thought to affect nuclear transfer efficiency (ES cell confluence and
      serum starvation of primary embryonic fibroblasts) were investigated to determine
      whether they had an effect on reprogramming in cell hybrids. Serum starvation of
      primary embryonic fibroblasts increased hybrid colony number 50-fold. ES cells
      were most effective at reprogramming when they contained a high proportion of
      cells in the S and G2/M phases of the cell cycle. These data suggest that nuclear
      reprogramming requires an initial round of somatic DNA replication of quiescent
      chromatin in the presence of ES-derived factors produced during S and G2/M
      phases.

PMID- 17009895
TI  - Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS
      rats.
AB  - Embryonic stem cells promise to provide a well-characterized and reproducible
      source of replacement tissue for human clinical studies. An early potential
      application of this technology is the use of retinal pigment epithelium (RPE) for
      the treatment of retinal degenerative diseases such as macular degeneration. Here
      we show the reproducible generation of RPE (67 passageable cultures established
      from 18 different hES cell lines); batches of RPE derived from NIH-approved hES
      cells (H9) were tested and shown capable of extensive photoreceptor rescue in an
      animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in
      which photoreceptor loss is caused by a defect in the adjacent retinal pigment
      epithelium. Improvement in visual performance was 100% over untreated controls
      (spatial acuity was approximately 70% that of normal nondystrophic rats) without
      evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT)
      and/or the creation of banks of reduced complexity human leucocyte antigen (HLA)
      hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs
      and/or immunomodulatory protocols.

PMID- 17009896
TI  - Inhibitors of histone deacetylases and DNA methyltransferases alter imprinted
      gene regulation in embryonic stem cells.
AB  - Pluripotent embryonic stem cells are able to differentiate into a variety of cell
      types, thereby making them a valuable source for transplantation medicine. Recent
      studies have reported the use of pharmacological agents, namely 5-Aza-Cytidine
      (5AzaC) and Trichostatin A (TSA), to guide embryonic stem (ES) cells to
      differentiate into specific cellular lineages. However, those drugs are known to
      be potent inhibitors of DNA methyltransferases and/or histone deacetylases. Since
      both epigenetic mechanisms are involved in the expression of imprinted genes in
      fetal and adult somatic tissues, it is essential to investigate further the role
      of these agents in regulating imprinted gene expression in embryonic cells.
      Embryonic stem cells were exposed to 5AzaC and TSA and analyzed for transcript
      abundance of a number of imprinted and non-imprinted marker genes. Most imprinted
      gene transcripts increased following exposure to 5AzaC or TSA alone and responded
      in either an additive or synergistic manner when exposed to both drugs together.
      Interestingly, transcript levels of several imprinted genes remained high and in
      some cases, increased further after drug removal or even after passaging the
      cells, indicating a long lasting and retarded effect on gene expression.
      Together, our results suggest that DNA methylation and histone acetylation play
      jointly an important epigenetic role in governing imprinted gene expression in
      embryonic stem cells. Moreover, these results describe the sensitivity and
      irreversibility of embryonic stem cells to epigenetic modifiers, highlighting
      potential risks for their use in therapeutic applications.

PMID- 17009898
TI  - Fluorescence-activated single cell sorting of human embryonic stem cells.
AB  - Human embryonic stem cells (hESC) are the subject of intense investigation for
      use in regenerative medicine, in toxicity testing, and as models for the study of
      human development. Automated cell sorting will enhance the isolation of
      homogenous pools of differentiated hESCs both for basic studies and for
      therapeutic applications. Sorting could also be used to deplete undifferentiated,
      potentially tumourigenic cells. However, hESCs are sensitive to single cell
      disaggregation and recover poorly when plated at clonal density. Here we report a
      method for successful semi-automated single cell sorting of hESCs. This method
      utilizes an ES-specific promoter-transgene construct and automated FACS-based
      single cell sorting and plating. Clonal recovery in physiologic oxygen (2%) was
      increased fourfold over room oxygen (21%; p < 0.01). This automated protocol will
      help to realize proposed hESC strategies that are hampered by low throughput and
      poor yields.

PMID- 17009897
TI  - Comparative studies on the mRNA expression of development-related genes in an
      individual mouse blastocyst with different developmental potential.
AB  - The evaluation of embryo morphology, widely used for selecting mammalian embryos
      before transfer, is not an adequate standard for selecting nuclear-transferred
      (NT) embryos. To search for markers useful for predicting the potential of NT
      embryos to develop into young, we examined the relation between the morphology of
      embryos with different developmental potential and gene expression of Oct 4,
      Nanog, Stat3, FGF4, Stella, and Sox2. In the present study, we examined
      pronuclear-exchanged blastocysts and morula blastomere, embryonic stem (ES) cell,
      and cumulus cell NT blastocysts, and in vivo-developed and in vitro-developed
      blastocysts. Based on the small variations in the gene expression levels among
      the in vivo-developed blastocysts, and the significant differences in gene
      expression between in vivo-developed (high developmental potential), and ES cell
      and cumulus cell NT blastocysts (low developmental potential), down-regulation of
      Sox2 and Oct4 genes is considered to be a candidate marker for the low potential
      of NT embryos to develop into young.

PMID- 17009899
TI  - A novel high-sensitivity diagnostic test for B-CLL.

PMID- 17009901
TI  - Amino-terminal pro-brain natriuretic peptide: a biomarker for diagnosis,
      prognosis and management of heart failure.
AB  - There is a substantial need for a diagnostic tool to aid in the early diagnosis
      of heart failure and in the recognition of those at risk for its development, as
      well as in guidance of therapy. Testing for amino-terminal pro-brain natriuretic
      peptide (NT-proBNP) has been recognized to have utility in the diagnosis,
      prognosis and management of heart failure. In addition, numerous other
      applications for NT-proBNP testing are now recognized, such as evaluation of
      patients with heart disease in the absence of heart failure, as well as the
      diagnostic and prognostic evaluation of patients with acute coronary syndromes or
      pulmonary thromboembolism.

PMID- 17009902
TI  - QuantiFERON-TB Gold: state of the art for the diagnosis of tuberculosis
      infection?
AB  - Tuberculosis (TB) remains a major threat to global health. The recently launched
      Global Plan to Stop Tuberculosis 2006-2015 highlights the need for accurate,
      simple and low-cost diagnostic tests for the detection of TB infection. For the
      first time in decades, new diagnostic tools have emerged that may facilitate this
      goal. The discovery of Mycobacterium tuberculosis-specific immunodominant
      antigens has led to the development of interferon gamma-release assays that have
      been shown to have high sensitivity and specificity for TB disease. This review
      focuses on the QuantiFERON-TB Gold tests and addresses the potential strengths
      and limitations of the current assays, summarizes the available evidence for
      their use and identifies areas of future research and development. Although
      representing an advance in TB diagnostics, with the potential to have a
      significant impact on global TB control, many issues remain unanswered. The cost
      of the tests and laboratory requirements may limit their use in developing
      countries. Most importantly, additional studies are needed in TB-endemic regions,
      particularly in high-risk persons such as children and individuals who are also
      co-infected with HIV.

PMID- 17009903
TI  - Use of nanotechnology for the development of novel cancer biomarkers.
AB  - Novel nanotechnologies can complement and augment existing genomic and proteomic
      techniques employed to analyze variations across different tumor types, thus
      offering the potential to distinguish between normal and malignant cells.
      Sensitive biosensors constructed out of nanoscale components (e.g.,
      nanocantilevers, nanowires and nanochannels) can recognize genetic and molecular
      events and have reporting capabilities, thereby offering the potential to detect
      rare molecular signals associated with malignancy. Such signals may then be
      collected for analysis by nanoscale harvesters that selectively isolate cancer
      related molecules from tissues. Another area with near-term potential for the
      early detection of cancer is the identification of mutations and genomic
      instability.

PMID- 17009904
TI  - Blood cardiac troponin in toxic myocardial injury: archetype of a translational
      safety biomarker.
AB  - A translational safety biomarker for toxic myocardial injury is needed in drug
      discovery and development. This need reflects the increasing recognition of
      occurrence of cardiotoxicities, prior lack of preclinical blood biomarkers for
      toxic cardiac injury, introduction of troponin as a biomarker, and regulatory and
      industry drivers. Cardiac troponin is considered the gold-standard biomarker in
      humans for cardiac injury due to ischemic injury and drug toxicity. It has been
      demonstrated to correlate highly with histopathological extent of injury, degree
      of impairment of cardiac function, and prognosis. Numerous studies have now
      clearly demonstrated that both cardiac troponin T and cardiac troponin I are
      sensitive and specific biomarkers of cardiac injury in laboratory animals. Their
      use is highly recommended for incorporation into preclinical drug-safety studies,
      especially whenever there is any history of cardiac effect in prior studies with
      a compound of the same or similar chemical or pharmacological class. The main
      caveats with respect to cross-species use of specific cardiac troponin assays are
      the need for species-specific validation, definition of cut-offs based on
      relevant assessments of imprecision and reference ranges or concurrent controls,
      and knowledge of the species-dependent kinetics of release into, and clearance
      from, the blood. Future development of high-sensitivity assays should determine
      whether minimal increases below a threshold concentration of troponin might
      reflect reversible myocardial effects.

PMID- 17009905
TI  - Microarray RNA transcriptional profiling: part II. Analytical considerations and
      annotation.
AB  - This review summarizes the various data filtration, transformation and
      normalization processes for different array platforms (cDNA, oligos, one- and two
      color), data analysis methods and their validation, and databases and annotation
      for RNA transcriptional profiling microarrays. This review is intended to
      introduce the beginner to the analyses and interpretation of gene expression
      studies using a nonmathematical approach for easier comprehension. Microarray
      analysis is not a trivial undertaking as there is no single method that works
      well for all, and results obtained from these analyses should be considered as a
      complement to other approaches.

PMID- 17009906
TI  - Pattern recognition and biomarker validation using quantitative 1H-NMR-based
      metabolomics.
AB  - The collection of global metabolic data and their interpretation (both spectral
      and biochemical) using modern spectroscopic techniques and appropriate
      statistical approaches, are known as 'metabolic profiling', 'metabonomics' or
      'metabolomics'. This review addresses 1H-nuclear magnetic resonance (NMR)-based
      metabolomic principles and their application in biomedical science, with special
      emphasis on their potential in translational research in transplantation,
      oncology, and drug toxicity or discovery. Various steps in metabolomics analysis
      are described in order to illustrate the types of biological samples, their
      respective handling and preparation for 1H-NMR analysis; provide a rationale for
      using pattern-recognition techniques (spectral database concept) versus
      quantitative 1H-NMR-based metabolomics (metabolite database concept); and
      identify necessary technological and logistical future developments that will
      allow 1H-NMR-based metabolomics to become an established tool in biomedical
      research and patient care.

PMID- 17009907
TI  - Use of gene expression microarrays for the study of acute leukemia.
AB  - Genetic lesions found in acute leukemia drive the pathology of the disease in
      addition to forming reliable classifications of prognosis. However, there is
      still a reasonable heterogeneity of response among cases with the same genetic
      lesion. Moreover, many leukemia cases have no detectable genetic marker and these
      cases have marked heterogeneity of response. How can we learn more about the
      genes and pathways involved with leukemogenesis and response in the midst of such
      complexity? Gene expression microarrays are experimental platforms that allow for
      the simultaneous evaluation of the thousands of mRNA transcripts (the
      'transcriptome'). This technology has revolutionized the study of leukemia,
      giving insight into genes and pathways involved in disease response and the
      biology involved in specific translocations.

PMID- 17009908
TI  - Signal amplification systems in immunoassays: implications for clinical
      diagnostics.
AB  - Biomarkers in physiological specimens serve as useful sensors for clinical
      diagnosis. Accurate detection of specific markers is crucial for the diagnosis of
      disease, monitoring drug therapy and patient screening. In vitro immunoassays are
      probably the most common, simple and relatively inexpensive serological tools
      used in clinical laboratories for the diagnosis and management of disease.
      Despite continued efforts to improve the performance of immunoassays in the past
      three decades, there is a need for highly sensitive assays that can detect the
      lowest levels of disease markers with greater accuracy. This review summarizes
      recent advances made towards increasing the sensitivity of immunoassays by
      amplifying detection signals, with implications for the development of highly
      sensitive diagnostic systems; it also discusses the principles of related
      methodologies.

PMID- 17009909
TI  - Rapid antigen detection testing in diagnosing group A beta-hemolytic
      streptococcal pharyngitis.
AB  - Group A beta-hemolytic streptococcus (GABHS) is the most common bacterial cause
      of acute pharyngitis. Clinical criteria alone are not reliable enough to diagnose
      GABHS pharyngitis. Microbiological-testing is required for correct diagnosis.
      Although a throat swab culture remains the gold standard for documenting the
      presence of GABHS, a significant disadvantage of the culture is the delayed time
      of 1-2 days to obtain results. Most rapid antigen detection tests can provide
      results in less than 15 min. Rapid identification and treatment of patients with
      GABHS pharyngitis can reduce the risk of the spread of disease, may shorten the
      duration of symptoms, decrease the incidence of suppurative complications,
      decrease the amount of time lost from school/work, decrease the inappropriate use
      of antibiotics, reduce patient/parent dissatisfaction and alleviate the need for
      costly follow-up visits. All rapid antigen detection tests involve extraction of
      the group-specific carbohydrate antigen from the GABHS cell wall and
      identification of the antigen by an immunological reaction. There are numerous
      rapid antigen detection testing methods, namely latex agglutination, enzyme
      immunoassay, optical immunoassay, chemiluminescent DNA probes and PCR methods.
      Most of the rapid antigen detection tests that are currently in use have an
      excellent specificity of greater than 95% and a sensitivity of greater than or
      equal to 90%. Owing to the high specificity of the rapid antigen detection tests,
      a positive rapid antigen detection test is accepted as adequate for the diagnosis
      of GABHS pharyngitis. Conversely, confirmation of a negative antigen detection
      test with a throat culture result is necessary, unless the physician has
      ascertained in his/her practice that the sensitivity of the rapid antigen test
      used is comparable with that of a throat culture.

PMID- 17009910
TI  - Clinical assessment of assays for diagnosis of herpes simplex infection.
AB  - It is becoming increasingly clear that the herpes simplex viruses (HSVs) 1 and 2
      constitute a major, global, public health problem, particularly as genital herpes
      is implicated in the causation of a significant percentage of onwards
      transmission of the HIV virus. A major factor in the transmission of HSV is that
      most carriers are unaware of their diagnosis. In the last few years, the
      development of nucleic acid amplification technology and type-specific antibody
      serology to test for HSV-1 and -2 has contributed significantly to the accurate
      diagnosis of these infections. Despite guidance to the contrary, there is still
      much use of less sensitive tests such as viral culture and antibody testing based
      on crude antigen. It is essential that we use the most sensitive and specific
      diagnostic tests if we are to curb this epidemic.

PMID- 17009911
TI  - Psychosis in Parkinson's disease: how should we treat it?

PMID- 17009912
TI  - New 'risk-score' method to predict dementia.

PMID- 17009913
TI  - Bupropion: pharmacology and therapeutic applications.
AB  - A total of 17 years after its introduction, bupropion remains a safe and
      effective antidepressant, suitable for first-line use. Bupropion undergoes
      metabolic transformation to an active metabolite, 4-hydroxybupropion, through
      hepatic cytochrome P450-2B6 (CYP2B6) and has inhibitory effects on cytochrome
      P450-2D6 (CYP2D6), thus raising concern for clinically-relevant drug
      interactions. Common side effects are nervousness and insomnia. Nausea appears
      slightly less common than with the SSRI drugs and sexual dysfunction is probably
      the least of any antidepressant. Bupropion is relatively safe in overdose with
      seizures being the predominant concern. The mechanism of action of bupropion is
      still uncertain but may be related to inhibition of presynaptic dopamine and
      norepinephrine reuptake transporters. The activity of vesicular monoamine
      transporter-2, the transporter pumping dopamine, norepinephrine and serotonin
      from the cytosol into presynaptic vesicles, is increased by bupropion and may be
      a component of its mechanism of action. Bupropion is approved for use in major
      depression and seasonal affective disorder and has demonstrated comparable
      efficacy to other antidepressants in clinical trials. Bupropion is also useful in
      augmenting a partial response to selective serotonin reuptake inhibitor
      antidepressants, although bupropion should not be combined with monoamine oxidase
      inhibitors. It may be less likely to provoke mania than antidepressants with
      prominent serotonergic effects. Bupropion is effective in helping people quit
      tobacco smoking. Anecdotal reports indicate bupropion may lower inflammatory
      mediators such as tumor necrosis factor-alpha, may lower fatigue in cancer and
      may help reduce concentration problems.

PMID- 17009914
TI  - Rituximab in the treatment of peripheral neuropathy associated with monoclonal
      gammopathy.
AB  - Peripheral neuropathy associated with immunoglobulin (Ig)M gammopathy and anti
      myelin-associated glycoprotein antibodies is frequently treatment-resistant and
      different treatment regimens carry substantial toxicity and side effects. More
      recently, the chimeric anti-CD20 monoclonal antibody rituximab has shown benefits
      in the treatment of peripheral neuropathy associated with IgM gammopathy with a
      favorable side-effect profile. There are no published reports of its use in the
      treatment of neuropathy associated with IgG and IgA gammopathies. Rituximab is
      usually given at 375 mg/m(2) intravenously with four weekly doses that may be
      repeated after 6-12 months. Large controlled studies are still pending but
      rituximab is an exciting and promising treatment offering another option in the
      treatment of peripheral neuropathy associated with IgM monoclonal gammopathy.

PMID- 17009915
TI  - Rotigotine for the treatment of Parkinson's disease.
AB  - Dopaminergic therapies, including levodopa and dopamine agonists, are the
      mainstays of therapy in Parkinson's disease. With the exception of the injectable
      short-acting dopamine agonist apomorphine, there is no other widely available non
      oral dopaminergic therapy. Rotigotine is a lipid-soluble, non-ergot, D3, D2, D1
      dopamine receptor agonist that has demonstrated efficacy as an alternative
      therapeutic option in both early and advanced Parkinson's disease. More
      importantly, it is uniquely formulated as a transdermal patch delivery system
      allowing for continuous, once-daily administration and better patient compliance.
      Preclinical and clinical trials have shown rotigotine to be a well-tolerated and
      effective treatment for early-stage Parkinson's disease. Rotigotine has also
      shown promise as adjunctive therapy with levodopa for the treatment of advanced
      Parkinson's disease.

PMID- 17009916
TI  - Zonisamide for the treatment of epilepsy.
AB  - The availability of new antiepileptic drugs with different mechanisms of action
      has widened our therapeutic choice, allowing better tailoring of treatment
      regimens to address specific needs. Zonisamide is the latest addition to the
      pharmacological management of epilepsy in Europe, following extensive clinical
      experience in Japan and the USA. This article reviews the structure, mechanism of
      action, pharmacokinetics and drug interactions of zonisamide. The four double
      blind, placebo-controlled trials in patients with drug-resistant focal seizures
      are also presented. They complement pre- and postmarketing studies conducted in
      Japan and provide clear-cut evidence that the drug has efficacy as an add-on
      treatment in this indication. Reports on zonisamide monotherapy and on the use of
      the drug for the control of several types of seizures (typical and atypical
      absences, tonic and myoclonic) and syndromes in children and adults are also
      commented on. These were all open-label studies, as is often the case with other
      antiepileptic drugs, dealing with treatment of epilepsy in children. The
      Japanese, US and European data provide a large database of safety information
      suggesting that the drug is well tolerated with mild-to-moderate adverse events
      (e.g., somnolence and dizziness). Nephrolithiasis appears to have a very low
      incidence and cutaneous reactions are rare. The available data provide an
      excellent foundation on which clinicians can build their knowledge on this drug,
      although the broad-spectrum efficacy of zonisamide needs to be confirmed through
      randomized trials.

PMID- 17009918
TI  - Listening to hypochondriasis and hearing health anxiety.
AB  - Although hypochondriasis is categorized as a somatoform disorder in the
      Diagnostic and Statistical Manual of Mental Disorders Fourth Edition--Text
      Revision (DSM-IV-TR) due to excessive focus on bodily symptoms for at least 6
      months, a contemporary conceptualization suggests that hypochondriasis represents
      an intense form of health anxiety. This article discusses the clinical
      presentation of hypochondriasis, etiological underpinnings and multiple
      maintaining factors, including physiological, cognitive and behavioral
      components. A cognitive-behavioral model of hypochondriasis as health anxiety and
      the empirically supported treatment based on the model are articulated. Future
      directions and informational resources are provided for both clinicians and
      patients.

PMID- 17009919
TI  - Nonsteroidal anti-inflammatory drugs in Parkinson's disease: possible involvement
      of quinone formation.
AB  - It has been revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) have
      neuroprotective properties based not only on their cyclooxygenase-inhibitory
      action, but also on other properties including their inhibitory effects on the
      synthesis of nitric oxide radicals and agonistic action for peroxisome
      proliferator-activated receptor gamma, in addition to some as yet unknown
      properties. Recently, a number of experimental and clinical studies have examined
      the neuroprotective effects of NSAIDs on the pathogenesis of several
      neurodegenerative diseases, including Parkinson's disease. In this article,
      various pharmacological effects of NSAIDs (except for their cyclooxygenase
      inhibitory action) are reviewed, and possible neuroprotective effects of NSAIDs
      on Parkinson's disease are discussed. The neurotoxicity of dopamine quinones, or
      DOPA quinones, has recently received attention as a dopaminergic neuron-specific
      oxidative stress that is known to play a role in the pathogenesis of Parkinson's
      disease and neurotoxin-induced parkinsonism. NSAIDs inhibit prostaglandin H
      synthase, thus suppressing dopamine oxidation and subsequent dopamine quinone
      formation. Therefore, this article also reviews possible suppressive effects of
      some NSAIDs against dopamine quinone generation.

PMID- 17009917
TI  - Early diagnostics and therapeutics for Alzheimer's disease--how early can we get
      there?
AB  - Alzheimer's disease (AD) is a major threat for the rapidly aging world
      population. AD is the leading cause of dementia and a major cause of death in
      developed countries. The disease puts a tremendous practical, emotional and
      financial burden on individuals and governments. Clinicians and researchers in
      the AD field face great challenges: the pathophysiological processes that cause
      AD are not well understood, definite diagnosis of AD requires autopsy, and
      therapeutic options are limited to treating the symptoms rather than the cause of
      the disease. Nevertheless, new insights into the earliest events that lead to
      development of AD increase hope that reliable diagnostics and efficacious
      therapies may emerge.

PMID- 17009920
TI  - Impaired regulation of immune responses in cognitive decline and Alzheimer's
      disease: lessons from genetic association studies.
AB  - Altered levels of cytokines and acute-phase proteins have been described in the
      blood and brain of patients with Alzheimer's disease. Microglia are resident
      cells of the brain and metabolic upregulation of these cells may play a crucial
      role in the development of the neurodegeneration associated with Alzheimer's
      disease. Studies focusing on gene polymorphisms of molecules with immune
      regulatory function have demonstrated an association with increased risk of the
      disease and confirmed the pivotal role of immune responses in Alzheimer's disease
      pathogenesis. Several gene variants may also influence the rate of the cognitive
      decline associated with the disease. A definite immune-related gene polymorphism
      profile may be a feature of a limited group of patients with early onset of the
      disease and fast clinical deterioration. Only this group of patients may benefit
      from anti-inflammatory treatment.

PMID- 17009921
TI  - Ubiquitin proteasome system as a pharmacological target in neurodegeneration.
AB  - Ubiquitinated protein aggregates are observed in the brains of Alzheimer's,
      Parkinson's and Huntington's disease patients and in other neurodegenerative
      disorders. These aggregates indicate that the ubiquitin proteasome system may be
      impaired in these diseases. To date no therapy is available that specifically
      targets this system, although preventing aggregate formation or stimulating the
      degradation of already formed aggregates by targeting components of the ubiquitin
      proteasome system is an attractive therapeutic approach. Here, we review the role
      of the ubiquitin proteasome system in aggregate formation with respect to
      neurodegenerative diseases, discussing the unfolded protein response, endoplasmic
      reticulum-associated degradation, aggresome formation and accumulation as well as
      aggregation and neurotoxicity of proteins involved in neurodegeneration. The
      potential of pharmacological intervention within this system in patients
      suffering from neurodegenerative diseases will be evaluated.

PMID- 17009922
TI  - Predictors of early mortality in patients with ischemic stroke.
AB  - Accurate predictors of early outcome in stroke patients have a number of
      important applications, such as introducing secondary prevention strategies,
      supporting treatment decisions or designing randomized clinical trials.
      Surprisingly, a generally accepted, reliable and well-validated mortality
      prediction model is still unavailable. This review outlines the most important
      predictors of in-hospital mortality that could be assessed at admission to
      hospital emergency room within 24 h of ischemic stroke onset. A number of factors
      are discussed such as nonmodifiable factors (e.g., age, gender and genetic
      factors); type of stroke and its severity - measured by different clinical score
      scales; predictive models; laboratory markers; special neuroradiological and
      neurophysiological tests; and comorbid conditions at admission and quality of
      hospital care.

PMID- 17009923
TI  - Review of the epidemiological literature on antidepressant use and breast cancer
      risk.
AB  - Based on evidence that antidepressants increase levels of prolactin and may
      promote the growth of mammary tumor cells, there has been concern that the use of
      these drugs may increase the risk of breast cancer. This article reviews the
      epidemiological evidence on the relationship between breast cancer risk and the
      use of the selective serotonin reuptake inhibitors, the tricyclic antidepressants
      and other antidepressants. Overall, the evidence does not support the hypothesis
      that the use of antidepressants increases the risk of breast cancer. There is a
      dearth of data on long-term selective serotonin reuptake inhibitor use. Since
      these drugs are commonly used, it is prudent public health policy to monitor
      breast cancer incidence among women using this class of drug for long durations.

PMID- 17009924
TI  - Innovations and recent trends in the treatment of ADHD.
AB  - Initiatives to develop better-tolerated, more efficacious pharmacological agents
      with improved drug delivery systems have driven recent research in attention
      deficit hyperactivity disorder (ADHD). While stimulants are the primary
      pharmacotherapy for ADHD, these drugs have a limited duration of action and a
      subset of patients will either fail to respond to these medications or have side
      effects that preclude their use. The development of atomoxetine, the first
      nonstimulant approved for ADHD, has been followed by additional innovative
      research, such as the methylphenidate transdermal system, modafinil, NRP-104 and
      cholinergic agents. This review highlights some of the recent trends in ADHD
      treatment and the current status of promising treatment options that may help to
      shape the future of ADHD treatment.

PMID- 17009925
TI  - Carbonyl reductases: the complex relationships of mammalian carbonyl- and quinone
      reducing enzymes and their role in physiology.
AB  - Carbonyl groups are frequently found in endogenous or xenobiotic compounds.
      Reactive carbonyls, formed during lipid peroxidation or food processing, and
      xenobiotic quinones are able to covalently modify DNA or amino acids. They can
      also promote oxidative stress, the products of which are thought to be an
      important initiating factor in degenerative diseases or cancer. Carbonyl groups
      are reduced by an array of distinct NADPH-dependent enzymes, belonging to several
      oxidoreductase families. These reductases often show broad and overlapping
      substrate specificities and some well-characterized members, e.g., carbonyl
      reductase (CBR1) or NADPH-quinone reductase (NQO1) have protective roles toward
      xenobiotic carbonyls and quinones because metabolic reduction leads to less toxic
      products, which can be further metabolized and excreted. This review summarizes
      the current knowledge on structure and function relationships of the major human
      and mammalian carbonyl reductases identified.

PMID- 17009926
TI  - Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the
      central nervous system.
AB  - Subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) are constructed
      from numerous subunit combinations that compose channel-receptor complexes with
      varied functional and pharmacological characteristics. Structural and functional
      diversity and the broad presynaptic, postsynaptic, and nonsynaptic locations of
      nAChRs underlie their mainly modulatory roles throughout the mammalian brain.
      Presynaptic and preterminal nicotinic receptors enhance neurotransmitter release,
      postsynaptic nAChRs contribute a small minority of fast excitatory transmission,
      and nonsynaptic nAChRs modulate many neurotransmitter systems by influencing
      neuronal excitability. Nicotinic receptors have roles in development and synaptic
      plasticity, and nicotinic mechanisms participate in learning, memory, and
      attention. Decline, disruption, or alterations of nicotinic cholinergic
      mechanisms contribute to dysfunctions such as epilepsy, schizophrenia,
      Parkinson's disease, autism, dementia with Lewy bodies, Alzheimer's disease, and
      addiction.

PMID- 17009927
TI  - Allosteric modulation of G protein-coupled receptors.
AB  - The past decade has witnessed a significant growth in the identification of
      allosteric modulators of G protein-coupled receptors (GPCRs), i.e., ligands that
      interact with binding sites that are topographically distinct from the
      orthosteric site recognized by the receptor's endogenous agonist. Because of
      their ability to modulate receptor conformations in the presence of orthosteric
      ligand, allosteric modulators can "fine-tune" classical pharmacological
      responses. This is advantageous in terms of a potential for engendering greater
      GPCR subtype-selectivity, but represents a significant challenge for detecting
      and validating allosteric behaviors. Although allosteric sites need not have
      evolved to accommodate endogenous ligands, there are a number of examples of
      where such modulators have been shown to contribute to physiological or
      pathophysiological processes. Studies are also beginning to unravel the
      structural basis of allosteric modulation of GPCRs. It remains to be determined
      whether such modulation represents interactions within monomers versus across
      dimers.

PMID- 17009928
TI  - Understanding circuit dynamics using the stomatogastric nervous system of
      lobsters and crabs.
AB  - Studies of the stomatogastric nervous systems of lobsters and crabs have led to
      numerous insights into the cellular and circuit mechanisms that generate rhythmic
      motor patterns. The small number of easily identifiable neurons allowed the
      establishment of connectivity diagrams among the neurons of the stomatogastric
      ganglion. We now know that (a) neuromodulatory substances reconfigure circuit
      dynamics by altering synaptic strength and voltage-dependent conductances and (b)
      individual neurons can switch among different functional circuits. Computational
      and experimental studies of single-neuron and network homeostatic regulation have
      provided insight into compensatory mechanisms that can underlie stable network
      performance. Many of the observations first made using the stomatogastric nervous
      system can be generalized to other invertebrate and vertebrate circuits.

PMID- 17009929
TI  - Overview of structure and function of mammalian cilia.
AB  - Cilia are membrane-bounded, centriole-derived projections from the cell surface
      that contain a microtubule cytoskeleton, the ciliary axoneme, surrounded by a
      ciliary membrane. Axonemes in multiciliated cells of mammalian epithelia are 9 +
      2, possess dynein arms, and are motile. In contrast, single nonmotile 9 + 0
      primary cilia are found on epithelial cells, such as those of the kidney tubule,
      but also on nonepithelial cells, such as chondrocytes, fibroblasts, and neurons.
      The ciliary membranes of all cilia contain specific receptors and ion channel
      proteins that initiate signaling pathways controlling motility and/or linking
      mechanical or chemical stimuli, including sonic hedgehog and growth factors, to
      intracellular transduction cascades regulating differentiation, migration, and
      cell growth during development and in adulthood. Unique motile 9 + 0 cilia, found
      during development at the embryonic node, determine left-right asymmetry of the
      body.

PMID- 17009930
TI  - Antimicrobial development and the risk-benefit assessment: recent adverse events
      and their implications.

PMID- 17009934
TI  - Drotrecogin alfa (activated) in the treatment of severe sepsis.
AB  - Severe sepsis is a common and frequently fatal condition. Evidence showing a link
      between the coagulation system and the inflammatory response to sepsis led to the
      development of drotrecogin alfa (activated) as an agent in the treatment of
      severe sepsis. Recent studies have shown that the mode of action is actually more
      complex than initially thought. This recombinant form of the natural
      anticoagulant, activated protein C, has been demonstrated to reduce mortality in
      a large randomized controlled, Phase III study involving 1690 patients, even
      though the results of this and subsequent studies and the licensing of
      drotrecogin alfa (activated) have generated considerable debate. Administration
      of drotrecogin alfa (activated) is associated with an increased risk of bleeding
      and its use is contraindicated in patients with a high risk of bleeding or recent
      hemorrhagic events.

PMID- 17009933
TI  - Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual
      NRTI backbone.
AB  - Truvada is the coformulation of tenofovir disoproxil fumarate (TDF; 300 mg) and
      emtricitabine (FTC; 200 mg) in a single tablet, providing the nucleotide backbone
      for once-daily dosing, as a component of highly active antiretroviral therapy
      (HAART). TDF (the bioavailable prodrug of tenofovir) is hydrolyzed to tenofovir
      intracellularly and phosphorylated to the active metabolite, tenofovir
      diphosphate. Tenofovir is a nucleotide analog of deoxyadenosine monophosphate,
      with activity against HIV-1, -2 and hepatitis B virus. FTC, the fluorinated
      derivative of lamivudine, is an analog of deoxycitidine, active against HIV-1, -2
      and hepatitis B virus. Their long half-lives in plasma and in peripheral blood
      mononuclear cells allow once-daily dosing. Both are eliminated renally.
      Resistance mutation K65R is selected for by tenofovir and confers a two- to
      fourfold reduced susceptibility to this drug. The incidence of K65R is low (3%)
      and has not been observed in clinical trials with the concomitant use of
      tenofovir and FTC. FTC selects for M184V mutation less frequently than
      lamivudine. Tenofovir drug interactions include increased exposure to didanosine
      and inferior immune recovery that preclude their concomitant use. Boosted
      protease inhibitors increase exposure to tenofovir without dose adjustment
      required. FTC has no significant drug interactions. They are not metabolized by
      cytochrome P450, which confers little potential for interactions with drugs
      metabolized by these enzymes. As tenofovir and FTC are renally eliminated, drugs
      eliminated by tubular secretion must be avoided. Both antiretrovirals, as
      individual agents and in coadministration have evidenced antiviral potency in
      clinical trials. Pivotal study 934 evidenced superior efficacy of the combination
      TDF/FTC/efavirenz (EFV) versus zidovudine/FTC/EFV. The toxicity profile of
      tenofovir and FTC has been extensively studied. Lipid profile is more favorable
      with tenofovir than thymidine analog. Tenofovir requires surveillance of
      glomerular filtration rate and dosing interval adjustment when creatinine
      clearance is less than 50 ml/min and avoidance less than 30 ml/min. Fat loss is
      less likely with tenofovir than with thymidine analog. Clinical trials have
      assessed the performance of the coformulation of TDF and FTC.

PMID- 17009935
TI  - Clevudine: a potent inhibitor of hepatitis B virus in vitro and in vivo.
AB  - Clevudine (CLV) is a nucleoside analog of the unnatural L-configuration that has
      potent anti-hepatitis B virus (HBV) activity in vitro and in vivo with a
      favorable toxicity profile in all species tested. In cell culture, CLV is readily
      phosphorylated to the corresponding 5'-triphosphate form of the compound. The
      mechanism of action of CLV involves the inhibition of the HBV polymerase by CLV
      5'-triphosphate. In vivo efficacy studies performed in the duck and woodchuck
      models showed marked, rapid inhibition of virus replication and no significant
      toxicity. In the woodchuck model, there was a dose-dependent delay in viral
      recrudescence and a reduction or loss of covalently closed circular DNA. In Phase
      II clinical studies, CLV was well tolerated and exhibited potent antiviral
      activity at all doses investigated. In Phase III studies in both hepatitis B e
      antigen (HBeAg)-positive and -negative patients, CLV 30 mg administered once
      daily demonstrated potent antiviral efficacy and significant biochemical
      improvement after only 24 weeks of therapy. These effects were sustained in a
      significant portion of the patients when therapy was stopped after 6 months with
      no viral rebound occurring in approximately 3 and 16% in HBeAg-positive and 
      negative patients, respectively. There have been no significant safety or
      tolerance issues associated with the drug in these studies. Future studies will
      investigate the safety and tolerance of CLV 30 mg given once daily over 48 weeks
      and longer.

PMID- 17009937
TI  - HIV testing in 2006: issues and methods.
AB  - Infection with HIV and subsequent development of AIDS is a pandemic. The Joint
      United Nations Program on HIV/AIDS together with the WHO and many relevant
      funding bodies demand that those infected should be reliably identified so that
      people who need, or will need, therapy may be provided for over time. This means
      that there is a renewed interest in testing for HIV and in laboratories'
      performances and quality. Whatever the conditions under which testing is
      performed, and whatever the levels of training, the tests and their outcomes must
      exhibit equivalent, high standards of performance and reliable results. This is
      regardless of whether testing is conducted in the most sophisticated laboratories
      (either diagnostic or transfusion screening) to voluntary testing and counseling
      centers where those conducting testing may not be technically trained. This is
      not currently the case, especially in some places where HIV is most prevalent. To
      achieve uniformly high performance standards, quality assurance programs are
      imperative, but currently not sufficiently valued to be well supported with
      adequate funding or human resources. Accurate HIV testing is a cornerstone of
      blood safety, diagnosis of infection, patient management and surveillance.

PMID- 17009938
TI  - Treatment options for chronic hepatitis B and C infection in children.
AB  - There has been a dramatic increase in treatment options for both chronic
      hepatitis B (CHB) and chronic hepatitis C (CHC) infection in adults over the past
      5-10 years, resulting in standardized regimes for initial treatment, relapsers
      and even infection in the setting of recurrence post-liver transplantation. These
      regimes have resulted in the halting of the disease progression, reduction in the
      risk of hepatocellular carcinoma and removal of these infections as a
      contraindication for liver transplantation. However, treatment in children must
      be considered carefully in the context of the natural history of these infections
      and host factors, particularly the immunological mileu, which may affect response
      to therapy. The as yet unknown long-term effects of medications must also be
      balanced with the probability of significant life-long morbidity or mortality
      from chronic hepatitis and its complications. Furthermore, the development of
      drug resistance, particularly in the case of CHB, has significant implications
      for the pediatric patient who may exhaust effective therapeutic options at a
      relatively young age. For these reasons, initiation of therapy must be based on
      sound criteria. Based on the current data, we recommend that therapy should be
      offered to children with CHB who have an elevation in alanine aminotransferase
      (>2-3 x upper limit of normal) for more than 6 months. Therapy with interferon
      alpha should be offered in the majority of cases with the aim of immune clearance
      as measured by early antigen seroconversion. By contrast, treatment indication
      for CHC in children remains controversial. If used, combination therapy with
      pegylated interferon and ribavirin is likely to produce the highest rates of
      sustained viral response.

PMID- 17009939
TI  - Novel methods to treat and prevent human papillomavirus infection.
AB  - The human papillomavirus (HPV), a ubiquitous sexually transmitted virus, is the
      causative agent for cervical dysplasia and carcinoma worldwide. Current treatment
      methods primarily utilize ablative and excisional procedures to remove
      dysplastic, HPV-infected cervical tissue. However, these procedures require
      intensive cytopathological surveillance and carry inherent risks of bleeding,
      infection and possible future pregnancy complications. Development of an
      effective vaccine against HPV would dramatically reduce the need for costly
      cytological and histological surveillance. HPV represents an ideal candidate for
      vaccine development, and current research efforts in the realm of prophylactic
      and therapeutic vaccine design show great promise. A host of various vaccine
      techniques are currently being developed and tested and, if effective, will have
      a significant impact on the incidence of cervical dysplasia and carcinoma.

PMID- 17009940
TI  - Treatment options for multidrug-resistant bacteria.
AB  - As a consequence of antibiotic overuse and misuse, nosocomial infections caused
      by multidrug-resistant bacteria represent a physician's nightmare throughout the
      world. No newer antimicrobials active against Pseudomonas aeruginosa, the main
      multidrug-resistant nosocomial pathogen, are available or under investigation.
      The only exceptions are linezolid, some newer glycopeptides (dalbavancin,
      oritavancin and telavancin) and daptomycin (a lipopeptide), which are active
      against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin
      resistant Enterococcus (VRE) strains, as well as tigecycline, a potent in vitro
      glycylcycline against MRSA, VRE, Acinetobacter baumannii and entended-spectrum
      beta-lactamase (ESBL)+ Enterobacteriaceae. Colistin, an antibiotic of the 1950s
      has been rediscovered by intensive care unit physicians for use against ESBL+
      Enterobacteriaceae, as well as against multidrug-resistant P. aeruginosa and A.
      baumannii isolates. Although success rates with colistin range between 50 and
      73%, almost all studies are retrospective. Immunostimulation efforts against S.
      aureus are still under development. As antibiotic research and development
      stagnate, rational policies for prescribing existing antibiotics plus strict
      infection control are the current mainstay efforts for preventing and combating
      multidrug-resistant bacterial infections.

PMID- 17009941
TI  - Antibiotic resistance in Neisseria gonorrhoeae is diminishing available treatment
      options for gonorrhea: some possible remedies.
AB  - Gonorrhea is essentially out of control in many settings and high disease rates
      are coupled with the spread of multiresistant gonococci. Increases in quinolone
      resistance have followed loss of the penicillins and tetracyclines as useful
      treatments. Decreasing susceptibility to third-generation cephalosporins is also
      reported. Over-reliance on antibiotic treatment as a disease control measure in
      settings with high disease rates and poor control of antibiotic usage is a
      significant contributor to the antimicrobial resistance reported. Conversely,
      containment of resistance is more likely to be achieved when combined with
      disease control principles shown to be effective. However, until a higher
      priority is given to funding for sexually transmitted diseases, this prospect is
      unlikely to eventuate and the possibility of untreatable gonorrhea becomes more
      real.

PMID- 17009942
TI  - Bacterial enteric infections in children: etiology, clinical manifestations and
      antimicrobial therapy.
AB  - Bacterial enteric infections have a huge impact on human health, particularly
      among the pediatric population. Despite the explosion of knowledge of the
      pathogenesis of bacterial enteric infections experienced in the past decade, the
      number of diarrheal episodes and childhood deaths reported continues to increase
      in many areas of the world. Specific antimicrobial therapy is indicated for
      certain confirmed infections, notably shigellosis, enterotoxigenic and
      enteroinvasive Escherichia coli infections, typhoid fever and cholera.
      Antimicrobial therapy may have a role in severe and prolonged gastrointestinal
      illness caused by nontyphoid Salmonella and Campylobacter. However, the use of
      antimicrobial agents may increase the risk of hemolytic uremic syndrome in
      children with E. coli O157:H7 infection. Bacterial genome sequencing and better
      understanding of the pathogenic mechanisms involved in the onset of diarrhea are
      leading to new preventive interventions, such as enteric vaccines, which may have
      a significant impact on the magnitude of this human plague.

PMID- 17009943
TI  - Treatment of Pseudomonas aeruginosa infection in critically ill patients.
AB  - Critically ill patients are on the increase in the present clinical setting.
      Aging of our population and increasingly aggressive medical and therapeutic
      interventions, including implanted foreign bodies, organ transplantation and
      advances in the chemotherapy of malignant diseases, have created a cohort of
      particularly vulnerable patients. Pseudomonas aeruginosa is one of the leading
      gram-negative organisms associated with nosocomial infections. This organism is
      frequently feared because it causes severe hospital-acquired infections,
      especially in immunocompromised hosts, and is often antibiotic resistant,
      complicating the choice of therapy. The epidemiology, microbiology, mechanisms of
      resistance and currently available and future treatment options for the most
      relevant infections caused by P. aeruginosa are reviewed.

PMID- 17009944
TI  - Current concepts in the treatment of bacterial meningitis beyond the neonatal
      period.
AB  - The epidemiology and treatment approach to bacterial meningitis has changed
      dramatically since the advent of antimicrobial therapy. New vaccines against
      meningeal pathogens have been implemented into national immunization programs
      successfully around the world. Antibiotic resistance has had a considerable
      impact on the efficacy of several therapeutic agents. In this review, the authors
      will discuss the principles of antibiotic chemotherapy, focusing on new agents
      for the treatment of penicillin-resistant pneumococci and adjunctive treatments
      to reduce the inflammatory response to bacterial infection of the meninges.

PMID- 17009945
TI  - Endogenous Candida endophthalmitis.
AB  - Intraocular Candida infections, although uncommon, represent an important
      clinical problem owing to the potential for visual loss, which can be bilateral.
      Candida chorioretinitis and endophthalmitis are complications of systemic
      candidiasis with extension of the fungal pathogens to the uvea and retina. Early
      diagnosis and prompt management significantly affect the visual prognosis for
      these patients. This review evaluates the current literature on Candida
      endophthalmitis and includes discussion on presentation, diagnosis and management
      strategies. New systemic and intravitreal antifungal agents are also reviewed in
      the context of the management of intraocular fungal infection.

PMID- 17009946
TI  - Treatment and prevention of malaria in pregnancy: opportunities and challenges.
AB  - Control of malaria in pregnancy through prevention or treatment may save lives of
      mothers and babies. Selection of drugs for treatment of infected pregnant women,
      or for prevention in exposed populations is problematic owing to resistance to
      established drugs and lack of pregnancy-specific safety and pharmacological data
      for new drugs. Encouragingly, a number of new drugs and combinations of drugs
      hold promise for effective treatment, but adequate data on their safety in
      pregnancy is currently lacking. Our principal challenges are to decide which
      drugs to develop for use in malaria treatment and prevention in pregnancy and to
      develop mechanisms to rapidly and comprehensively evaluate their safety.
      Prevention of pregnancy malaria by vaccination may also become possible, but
      targets must be closely defined, and strategies developed to test candidates
      against meaningful end points.

PMID- 17009947
TI  - Bacterial capsular antigens. Structural patterns of capsular antigens.
AB  - Structural patterns of bacterial capsular antigens including capsular
      polysaccharides and exoglycans are given in this review. In addition, the
      immunological activity of capsular antigens and their role in type specificity of
      bacteria are discussed.

PMID- 17009948
TI  - Capsular antigens of bacteria. Capsular antigens as the basis of vaccines against
      pathogenic bacteria.
AB  - The role of bacterial capsular antigens represented in capsular polysaccharides
      and exoglycans in pathogenicity and virulence of bacteria is discussed in this
      review. Using capsular antigens for vaccines against severe diseases caused by
      capsular microorganisms is considered in detail. The use of conjugates of
      capsular polysaccharides and their fragments with proteins and peptides for
      vaccine as well as using liposomes as adjuvants for the capsular antigens are
      described. Data concerning structural elucidation of bacterial capsular antigens
      are given in the first part of this review.

PMID- 17009949
TI  - Active defense under oxidative stress. The antioxidant responsive element.
AB  - This review considers the mechanisms and factors that stimulate transcription of
      genes regulated by the antioxidant responsive element (ARE). The latter is
      important for cell defense under conditions of oxidative stress and also for
      detoxification of electrophilic xenobiotics. There are differences in regulation
      of intracellular homeostasis involving Nrf2-mediated activation of ARE and other
      redox-sensitive factors (NF-kappaB and AP-1).

PMID- 17009950
TI  - High molecular mass exopolyphosphatase from the cytosol of the yeast
      Saccharomyces cerevisiae is encoded by the PPN1 gene.
AB  - It has been shown that the high molecular mass exopolyphosphatase localized in
      cytosol of the yeast Saccharomyces cerevisiae is encoded by the PPN1 gene. This
      enzyme is expressed under special culture conditions when stationary phase cells
      are passing on to new budding on glucose addition and phosphate excess. The
      enzyme under study releases orthophosphate from the very beginning of
      polyphosphate hydrolysis.

PMID- 17009951
TI  - Two soluble pyrophosphatases in Vibrio cholerae: transient redundancy or enduring
      cooperation?
AB  - Soluble pyrophosphatases (PPases), which are essential for cell life, comprise
      two evolutionarily unrelated families (I and II). Prokaryotic genomes generally
      contain a single PPase gene encoding either family I or family II enzyme.
      Surprisingly, four Vibrionales species, including the human pathogen Vibrio
      cholerae, contain PPase genes of both families. Here we show that both genes are
      transcriptionally active in V. cholerae, and encode functional PPases when
      expressed in Escherichia coli. In contrast, only the family I PPase protein is
      detected in V. cholerae under our experimental conditions. Phylogenetic analyses
      indicate that family II enzymes are not native to gamma-proteobacteria, but are
      of benefit to the marine species of this bacterial class. In this context, we
      favor the hypothesis that in the course of evolution, family II PPase was
      laterally transferred to the Vibrionales ancestor and partially degenerated due
      to functional redundancy, but nevertheless remained fixed as an adjunct to the
      family I enzyme.

PMID- 17009952
TI  - Two fused proteins combining Stichopus japonicus arginine kinase and rabbit
      muscle creatine kinase.
AB  - Two fused proteins of dimeric arginine kinase (AK) from sea cucumber and dimeric
      creatine kinase (CK) from rabbit muscle, named AK-CK and CK-AK, were obtained
      through the expression of fused AK and CK genes. Both AK-CK and CK-AK had about
      50% AK activity and about 2-fold K(m) values for arginine of native AK, as well
      as about 50% CK activity and about 2-fold K(m) values for creatine of native CK.
      This indicated that both AK and CK moieties are fully active in the two fused
      proteins. The structures of AK, CK, AK-CK, and CK-AK were compared by collecting
      data of far-UV circular dichroism, intrinsic fluorescence, 1-anilinonaphthalene-8
      sulfonate binding fluorescence, and size-exclusion chromatography. The results
      indicated that dimeric AK and CK differed in the maximum emission wavelength, the
      exposure extent of hydrophobic surfaces, and molecular size, though they have a
      close evolutionary relationship. The structure and thermodynamic stability of AK,
      CK, AK-CK, and CK-AK were compared by guanidine hydrochloride (GdnHCl) titration.
      Dimeric AK was more dependent on the cooperation of two subunits than CK
      according to the analysis of residual AK or CK activity with GdnHCl concentration
      increase. Additionally, AK and CK had different denaturation curves induced by
      GdnHCl, but almost the same thermodynamic stability. The two fused proteins, AK
      CK and CK-AK, had similar secondary structure, tertiary structure, molecular
      size, structure, and thermodynamic stability, which indicated that the expression
      order of AK and CK genes might have little effect on the characteristics of the
      fused proteins and might further verify the close relationship of dimeric AK and
      CK.

PMID- 17009953
TI  - Mechanism of activation of cytochrome C peroxidase activity by cardiolipin.
AB  - In this work, the actions of bovine heart cardiolipin, synthetic tetraoleyl
      cardiolipin, and a nonspecific anionic detergent sodium dodecyl sulfate (SDS) on
      cytochrome c (Cyt c) peroxidase activity recorded by chemiluminescence in the
      presence of luminol and on the Fe...S(Met80) bond whose presence was estimated by
      a weak absorption band amplitude with peak at 695-700 nm (A(695)) were compared.
      A strict concurrency between Fe...S(Met80) breaking (A(695)) and cytochrome
      peroxidase activity enhancement was shown to exist at cardiolipin/Cyt c and
      SDS/Cyt c molar ratios of 0 : 1 to 50 : 1 (by chemiluminescence). Nevertheless,
      when A(695) completely disappeared, Cyt c peroxidase activity under the action of
      cardiolipin was 20 times more than that under the action of SDS, and at low
      ligand/protein molar ratios (=4), SDS failed to activate peroxidase activity
      while cardiolipin enhanced Cyt c peroxidase activity 16-20-fold. A(695) did not
      change on Cyt c binding with liposomes consisting of tetraoleyl cardiolipin and
      phosphatidylcholine (1 : 10 : 10), while peroxidase activity was enhanced by a
      factor of 8. Breaking of 70% of the Fe...S(Met80) bonds resulted in only
      threefold enhancement of peroxidase activity. Cardiolipin-activated Cyt c
      peroxidase activity was reduced by high ionic strength solution (1 M KCl). The
      aggregated data suggest that cardiolipin activating action is caused, first, by a
      nonspecific effect of Fe...S(Met80) breaking as the result of conformational
      changes in the protein globule caused by the protein surface electrostatic
      recharging by an anionic amphiphilic molecule, and second, by a specific
      acceleration of the peroxidation reaction which is most likely due to enhanced
      heme accessibility for H(2)O(2) as a result of the hydrophobic interaction
      between cardiolipin and cytochrome.

PMID- 17009954
TI  - Cardiolipin activates cytochrome c peroxidase activity since it facilitates
      H(2)O(2) access to heme.
AB  - In this work, the effect of liposomes consisting of tetraoleyl cardiolipin and
      dioleyl phosphatidylcholine (1 : 1, mol/mol) on the rate of three more reactions
      of Cyt c heme with H2O2 was studied: (i) Cyt c (Fe2+) oxidation to Cyt c (Fe3+),
      (ii) Fe...S(Met80) bond breaking, and (iii) heme porphyrin ring decomposition. It
      was revealed that the rates of all those reactions increased greatly in the
      presence of liposomes containing cardiolipin and not of those consisting of only
      phosphatidylcholine, and approximately to the same extent as peroxidase activity.
      These data suggest that cardiolipin activates specifically Cyt c peroxidase
      activity not only because it promotes Fe...S(Met80) bond breaking but also
      facilitates H2O2 penetration to the reaction center.

PMID- 17009955
TI  - Biochemical characteristics of Escherichia coli ATP synthase with insulin peptide
      A fused to the globular part of the gamma-subunit.
AB  - The codon 5383-5385 (CCG) in the atpC gene of the unc operon of Escherichia coli
      cells was replaced with the sequence encoding peptide A of human insulin. The
      foreign protein fused to the middle part of the gamma-subunit of ATP synthase
      affects neither biosynthesis of the chimeric polypeptide nor the integration of
      the EF(0) x F(1) enzyme into the membranes of the E. coli cells. The inserted
      peptide A does not inhibit the process of oxidative phosphorylation. The ATPase
      activity of the mutant EF(0) x F(1) enzyme was equal to that of the wild-type
      enzyme and was regulated by modifiers in the similar way, suggesting that the
      space in the stalk area of F(0)/F(1) interaction is enough for the introduction
      of an additional oligopeptide without changing catalytic properties of the ATP
      synthase.

PMID- 17009956
TI  - Effect of hydrogen peroxide on antioxidant enzyme activities in Saccharomyces
      cerevisiae is strain-specific.
AB  - The effect of hydrogen peroxide on the survival and activity of antioxidant and
      associated enzymes in Saccharomyces cerevisiae has been studied. A difference
      found in the response of wild-type yeast strains treated with hydrogen peroxide
      was probably related to the different protective effects of antioxidant enzymes
      in these strains. Exposure of wild-type YPH250 cells to 0.25 mM H(2)O(2) for 30
      min increased activities of catalase and superoxide dismutase (SOD) by 3.4- and 2
      fold, respectively. However, no activation of catalase in the EG103 strain, as
      well as of SOD in the YPH98 and EG103 wild strains was detected, which was in
      parallel to lower survival of these strains under oxidative stress. There is a
      strong positive correlation (R(2) = 0.95) between activities of catalase and SOD
      in YPH250 cells treated with different concentrations of hydrogen peroxide. It is
      conceivable that catalase would protect SOD against inactivation caused by
      oxidative stress and vice versa. Finally, yeast cell treatment with hydrogen
      peroxide can lead to either a H(2)O(2)-induced increase in activities of
      antioxidant and associated enzymes or their decrease depending on the H(2)O(20
      concentration used or the yeast strain specificity.

PMID- 17009957
TI  - Hepatitis C virus RNA-dependent RNA polymerase: study on the inhibition mechanism
      by pyrogallol derivatives.
AB  - Pyrogallol reversibly and noncompetitively inhibits the activity of the hepatitis
      C RNA-dependent RNA polymerase. Based on molecular modeling of the inhibitor
      binding in the active site of the enzyme, the inhibition was suggested to be
      realized via chelation of two magnesium cations involved in the catalysis at the
      stage of the phosphoryl residue transfer. The proposed model allowed us to
      purposefully synthesize new derivatives with higher inhibitory capacity.

PMID- 17009958
TI  - Role of C-terminal sequence of cytochrome P450scc in folding and functional
      activity.
AB  - To elucidate the role of Arg472 and C-terminal sequence of the mature form of
      cytochrome P450scc, a mitochondrial cytochrome P450, in the present work we have
      performed sequential removal of the C-terminal amino acid residues of the
      hemeprotein and evaluated their functional role in folding and catalysis. The
      removal of 2, 4, 7, or 9 amino acid residues (cytochrome P450scc mutants Delta2,
      Delta4, Delta7, and Delta9) does not significantly affect the physicochemical
      properties of the truncated forms of cytochrome P450scc, but results in
      significant increase in the expression level of the hemeprotein in Escherichia
      coli (Delta4 cytochrome P450scc mutant). However, removal of 10 C-terminal amino
      acid residues (Delta10 cytochrome P450scc) of mature form of cytochrome P450scc
      (replacement of codon for Arg472 for stop-codon) is followed by loss of the
      ability for correct folding in E. coli. Based on these data, it is concluded that
      the C-terminal amino acid residues of cytochrome P450scc (DeltaArg472-Ala481)
      play an important role in correct recombinant protein folding and heme binding by
      cytochrome P450scc during its expression in E. coli, while folding of
      mitochondrial cytochrome P450scc during its heterologous expression in bacterial
      cells is more similar to the folding of prokaryotic soluble cytochrome P450's
      than to microsomal cytochrome P450's.

PMID- 17009959
TI  - Peculiarities of proteasome pool formation in rat spleen and liver during
      postnatal development.
AB  - Changes in the specific activity and amounts of 26S and 20S proteasome pools in
      rat spleen and liver during postnatal development and appearance in them of
      immune subunits were studied. Two decreases in chymotrypsin-like activity of the
      proteasome pools were recorded during the first three weeks after birth. The
      activity minimum fell on the 11th and 19th days, and the first decrease was more
      prolonged and pronounced than the second. The decrease in the specific activity
      of the 26S proteasome pools was associated with a reduction of their quantity.
      The 20S proteasome pools displayed no such decreases. Noticeable quantities of
      immune subunits LMP7 and LMP2 were revealed by Western blotting in the spleen on
      the 7th day and on the 19th day in the liver, concurrently with the beginning of
      the decrease in the proteasome activity. It was concluded that during the first
      three weeks of postnatal development the proteasome pools in rat spleen and liver
      were replaced twice, and in the spleen (a lymphoid organ) a qualitatively new
      pool containing immune subunits appeared nearly two weeks earlier than in the
      liver (a non-lymphoid organ). The appearance of immune proteasomes in different
      organs and tissues during some weeks after birth seems to explain the immune
      system inefficiency during embryogenesis and early postnatal development.

PMID- 17009960
TI  - Role of polyamines in formation of multiple antibiotic resistance of Escherichia
      coli under stress conditions.
AB  - Under stress conditions, polyamines decreased the permeability of the outer
      membrane of Escherichia coli. This effect is caused by at least three mechanisms
      providing for an increase in the resistance to antibiotics transported through
      porin channels (fluoroquinolones, beta-lactams): a positive modulation of the
      gene micF transcription (its product antisense RNA inhibits the synthesis of
      porin proteins on the translational level); a positive effect on the cell content
      of the multiple stress resistance factor sigma(S) (it is accompanied by a
      decrease in the porin transport because of suppression of ompF transcription and
      induction of cadaverine synthesis); a direct inhibition of the transport activity
      of porin channels. The production of cadaverine in E. coli cells significantly
      increased in response to various antibiotics, and this was likely to be a
      manifestation of oxidative stress.

PMID- 17009961
TI  - Purification and membrane reconstitution of catalytically active Menkes copper
      transporting P-type ATPase (MNK; ATP7A).
AB  - The MNK (Menkes disease protein; ATP7A) is a major copper- transporting P-type
      ATPase involved in the delivery of copper to cuproenzymes in the secretory
      pathway and the efflux of excess copper from extrahepatic tissues. Mutations in
      the MNK (ATP7A) gene result in Menkes disease, a fatal neurodegenerative copper
      deficiency disorder. Currently, detailed biochemical and biophysical analyses of
      MNK to better understand its mechanisms of copper transport are not possible due
      to the lack of purified MNK in an active form. To address this issue, we
      expressed human MNK with an N-terminal Glu-Glu tag in Sf9 [Spodoptera frugiperda
      (fall armyworm) 9] insect cells and purified it by antibody affinity
      chromatography followed by size-exclusion chromatography in the presence of the
      non-ionic detergent DDM (n-dodecyl beta-D-maltopyranoside). Formation of the
      classical vanadate-sensitive phosphoenzyme by purified MNK was activated by Cu(I)
      [EC50=0.7 microM; h (Hill coefficient) was 4.6]. Furthermore, we report the first
      measurement of Cu(I)-dependent ATPase activity of MNK (K0.5=0.6 microM; h=5.0).
      The purified MNK demonstrated active ATP-dependent vectorial 64Cu transport when
      reconstituted into soya-bean asolectin liposomes. Together, these data
      demonstrated that Cu(I) interacts with MNK in a co-operative manner and with high
      affinity in the sub-micromolar range. The present study provides the first
      biochemical characterization of a purified full-length mammalian copper
      transporting P-type ATPase associated with a human disease.

PMID- 17009962
TI  - ZZ domain of dystrophin and utrophin: topology and mapping of a beta-dystroglycan
      interaction site.
AB  - Dystrophin forms part of a vital link between actin cytoskeleton and
      extracellular matrix via the transmembrane adhesion receptor dystroglycan.
      Dystrophin and its autosomal homologue utrophin interact with beta-dystroglycan
      via their highly conserved C-terminal cysteine-rich regions, comprising the WW
      domain (protein-protein interaction domain containing two conserved tryptophan
      residues), EF hand and ZZ domains. The EF hand region stabilizes the WW domain
      providing the main interaction site between dystrophin or utrophin and
      dystroglycan. The ZZ domain, containing a predicted zinc finger motif, stabilizes
      the WW and EF hand domains and strengthens the overall interaction between
      dystrophin or utrophin and beta-dystroglycan. Using bacterially expressed ZZ
      domain, we demonstrate a conformational effect of zinc binding to the ZZ domain,
      and identify two zinc-binding regions within the ZZ domain by SPOTs overlay
      assays. Epitope mapping of the dystrophin ZZ domain was carried out with new
      monoclonal antibodies by ELISA, overlay assay and immunohistochemistry. One
      monoclonal antibody defined a discrete region of the ZZ domain that interacts
      with beta-dystroglycan. The epitope was localized to the conformationally
      sensitive second zinc-binding site in the ZZ domain. Our results suggest that
      residues 3326-3332 of dystrophin form a crucial part of the contact region
      between dystrophin and beta-dystroglycan and provide new insight into ZZ domain
      organization and function.

PMID- 17009963
TI  - Clinical application of oxaliplatin in epithelial ovarian cancer.
AB  - Platinum remains the most active drug class in ovarian cancer treatment; however,
      new single-agent and combination therapies are needed to improve the clinical
      outcome of ovarian cancer therapies. Oxaliplatin, a third-generation platinum
      derivative, has shown effective antitumor activity and a favorable toxicity
      profile in epithelial ovarian cancer. Preclinical evidence of the synergistic
      cytotoxic effect of oxaliplatin in combination with several other
      chemotherapeutic agents and clinical evidence of the absence of any dose-limiting
      hematologic toxicity associated with this agent have made oxaliplatin an
      attractive compound for combination agent therapy. This article reviews the
      current status of the clinical application of oxaliplatin alone and in a
      combination regimen in epithelial ovarian cancer treatment.

PMID- 17009964
TI  - Identification of genes associated with ovarian cancer metastasis using
      microarray expression analysis.
AB  - Although the transition from early- to advanced-stage ovarian cancer is a
      critical determinant of survival, little is known about the molecular
      underpinnings of ovarian metastasis. We hypothesize that microarray analysis of
      global gene expression patterns in primary ovarian cancer and metastatic omental
      implants can identify genes that underlie the metastatic process in epithelial
      ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the
      molecular alterations that underlie omental metastasis from 47 epithelial ovarian
      cancer samples collected from multiple sites in 20 patients undergoing primary
      surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty
      six genes demonstrated differential expression between ovarian and omental
      samples (P < 0.01), and twenty of these 56 differentially expressed genes have
      previously been implicated in metastasis, cell motility, or cytoskeletal
      function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian
      statistical tree analysis was used to identify a 27-gene expression pattern that
      could accurately predict the site of tumor (ovary versus omentum). This
      predictive model was evaluated using an external data set. Nine of the 27
      predictive genes have previously been shown to be involved in oncogenesis and/or
      metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray
      findings were validated by real-time quantitative PCR. We conclude that gene
      expression patterns that distinguish omental metastasis from primary epithelial
      ovarian cancer can be identified and that many of the genes have functions that
      are biologically consistent with a role in oncogenesis, metastasis, and p53 gene
      networks.

PMID- 17009965
TI  - Mode of detection of recurrent gynecological malignancy: Does routine follow-up
      delay diagnosis and treatment?
AB  - To investigate value of routine scheduled follow-up in detecting recurrent
      gynecological cancer, the National Group of Gynaecology NSSG Leads conducted a
      national prospective audit of the mode of detection of disease recurrence under
      the auspices of the Department of Health Cancer Services Collaborative. Two
      hundred fourteen responses were received from 16 of 34 cancer networks in England
      in addition to one center from Wales between August 2004 and October 2005. Only
      42.5% of disease recurrences was detected at routine follow-up. Only 26.2% was
      diagnosed during an unscheduled (expedited) clinic appointment, while 19.2% was
      diagnosed by another professional group and 12.1% by "other" means (routine Ca125
      or imaging). Only 77.1% of patients had symptoms at the time of detection of
      recurrent disease. Sixty-one patients (28.5%) complained of symptoms when they
      attended for routine scheduled follow-up. This data suggest that if these
      patients had recognized the significance of these symptoms and requested early
      clinic review, the diagnosis may have been expedited. Diagnosis of recurrence may
      be delayed for a significant proportion of women because they await a routine
      scheduled follow-up clinic attendance to report the development of symptoms.
      Patient-initiated follow-up may provide a more reactive and flexible model of
      care that encourages women to present as soon as symptoms are experienced. This
      model will be assessed in the UK in a large, multicenter, randomized controlled
      trial, Follow-up in Gynaecological cancer Units: Randomised controlled trial for
      Endometrium (FIGURE trial).

PMID- 17009966
TI  - Measurement of vaginal length: Reliability of the vaginal sound--a Gynecologic
      Oncology Group study.
AB  - A decrease in vaginal length associated with treatments for gynecological
      malignancies, particularly pelvic radiotherapy, negatively impacts sexuality.
      Research into this important problem has been hampered by a lack of
      instrumentation to measure vaginal length. The Gynecologic Oncology Group
      recently evaluated the reliability of an instrument, the "vaginal sound,"
      designed to measure vaginal length. Eighty-eight physicians and nurses attended a
      training session in the use of the vaginal sound that included a clinical
      practicum with live models. Reliability was assessed at the time of the
      practicum. The instrument performed well, with vaginal lengths in models without
      cancer in the upper range of normal as documented by Masters and Johnson. The
      vaginal sound also appeared to be sensitive to hypothesized changes in vaginal
      length. Interrater reliability was high with intraclass correlation coefficients
      of 0.88 among instructors and 0.76 among trainees. In conclusion, the vaginal
      sound is a simple, yet reproducible measure and adds methodologic rigor to
      studies of vaginal length.

PMID- 17009967
TI  - Ovarian cancer--can intraperitoneal therapy be regarded as new standard in
      Germany?
AB  - The German Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) and the two German
      cooperative study groups (AGO-OVAR and NOGGO) performed a review of the currently
      available literature on intraperitoneal first-line treatment in advanced ovarian
      cancer to consider if this new option should be incorporated into the German
      guidelines for treatment of ovarian cancer.

PMID- 17009968
TI  - Intraperitoneal chemotherapy for advanced epithelial ovarian cancer: A Canadian
      perspective.
AB  - The objectives of this study were to: a) assess the position of Canadian
      gynecological oncologists (GOC) toward intraperitoneal (IP) chemotherapy as
      primary treatment for ovarian cancer, b) initiate a process of communication
      among GOC, and c) assess the perception of barriers to implementing IP
      chemotherapy across Canada. An electronic practice survey was mailed to all GOC
      in January 2006. The response rate was 62%. GOC accept IP chemotherapy as the
      standard of care in the primary treatment of optimally debulked epithelial
      ovarian cancer. The majority of respondents were working on implementation
      strategies at their local institutions. The cost of administration and use of
      additional resources were identified as sources of moderate and high concerns,
      respectively. Moderate concerns were expressed with regard to the management of
      systemic and local toxicity, catheter complications, patients' acceptance, and
      quality of life. Catheter insertion issues were of low concern to most
      respondents. Previous experience with IP administration did not significantly
      impact the perceived level of concern. GOC support the use of IP chemotherapy for
      appropriate patients with ovarian cancer. This survey identifies important
      implementation challenges of IP therapy for Canada, and processes must be
      developed before successful delivery of IP chemotherapy can be realized. This
      survey serves to initiate a process of communication among GOC. A collaborative
      effort will be needed to facilitate this change in practice. Further study of the
      implementation process is warranted as more experience is gained with this
      modality of treatment.

PMID- 17009969
TI  - Outcomes of gynecologic oncology patients admitted to the intensive care unit
      following surgery: A university teaching hospital experience.
AB  - The objective of this study was to determine the outcomes of gynecological
      oncology patients requiring intensive care unit (ICU) admission following
      surgery. A computerized database identified postsurgical ICU admissions from
      January 1, 1999 to December 31, 2004 at a university hospital. Abstracted data
      included: demographics, preoperative diagnosis, reason(s) for ICU admission,
      consultations, interventions, length of stay (LOS), Acute Physiology and Chronic
      Health Evaluation (APACHE) II score, and 30-day mortality. Statistical analysis
      was performed with the Student's t-test. A total of 185 surgical gynecological
      oncology ICU patients was identified. Median age was 60 years (range, 21-92
      years), and 63% of patients were white. Only 72% of patients had ovarian,
      endometrial, or cervical cancer. The most common indications for ICU admission
      were volume resuscitation (108 patients) and respiratory insufficiency (80
      patients). Median ICU LOS was 1 day (range, 1-55 days). Patients surviving their
      hospital admission had a mean APACHE II score of 11.5 (range, 2-37) compared to a
      mean of 21.2 (range, 13-44) for patients who died prior to hospital discharge (P
      < 0.001). The overall mortality rate was 12%. A substantial number of
      gynecological oncology patients will be admitted to the ICU following surgery.
      Patient outcomes are favorable if APACHE II scores are low and ICU LOS is short.

PMID- 17009970
TI  - Survival in ovarian cancer in Wales: Prior to introduction of all Wales
      guidelines.
AB  - The objective of the study was to review referral practice, overall management,
      and survival in women with suspected ovarian cancer in Wales. This study was done
      prior to introduction of cancer management guidelines in the region. A
      confidential study questionnaire was sent to 20 participating hospitals. Data on
      287 consecutive women with suspected ovarian cancer were collected, of which 250
      women underwent primary laparotomy. Information was obtained on referral pattern,
      preoperative investigations, place of primary surgery, specialty of the primary
      surgeon, surgical parameters recorded at the time of operation, a final overall
      stage, adjuvant treatment, and survival outcome. There was a wide variation in
      referral practice and management of ovarian cancer in Wales. Stage of the
      disease, attempt at optimal debulking, residual disease, management by a cancer
      centre multidisciplinary team, and platinum-based chemotherapy were associated
      with improved overall survival and progression-free survival. More women were
      alive if managed in the cancer centre at 1 and 3 year after diagnosis (P =
      0.022). This study has highlighted the acute issue of the standards of clinical
      care in the area of ovarian cancer management and will emphasize the
      implementation of better care pathways for ovarian cancers.

PMID- 17009971
TI  - Inhibition of nuclear factor-kappaB by an antioxidant enhances paclitaxel
      sensitivity in ovarian carcinoma cell line.
AB  - The objective of this study was to determine whether paclitaxel and a strong
      antioxidant, pyrrolidinedithiocarbamate (PDTC), can affect the activation of
      nuclear factor-kappa B (NF-kappaB) in SKOV-3 human ovarian cancer cell line and
      the effect of these two agents on the growth and apoptosis of the cancer cells.
      The cells were treated with various concentrations of paclitaxel and/or PDTC at
      various time intervals. Following treatments, cell growth and apoptosis were
      determined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulphonyl)
      2H-tetrazolium (WST-8) (WST) assay and flow cytometry, respectively. Western blot
      assay was used to determine the nuclear p65 protein and cytoplasmic IkappaB-alpha
      protein. High doses of PDTC significantly inhibited the growth of SKOV-3 cells
      and caused apoptosis. Paclitaxel and lower doses of PDTC combined demonstrated
      additive inhibition of cell growth and increased levels of apoptosis. Treatment
      of paclitaxel alone showed increased nuclear p65 protein and decreased
      cytoplasmic IkappaB-alpha protein expression, while pretreatment of PDTC reversed
      this function. PDTC blocks the paclitaxel-induced activation of NF-kappaB leading
      to increased chemosensitivity to paclitaxel and enhanced apoptosis. Combining
      antioxidants and paclitaxel has significant potential to overcome the risk of
      paclitaxel resistance.

PMID- 17009972
TI  - Expression of aminopeptidase N/CD13 in human ovarian cancers.
AB  - Aminopeptidase N/CD13 (EC 3.4.11.2) is suggested to play a role in cancer cells
      invasion, and its activity can be inhibited using specific inhibitors. CD13
      inhibitors evoke apoptosis of CD13-positive cancer cells. However, expression of
      CD13 has not been described in specimens obtained from ovarian carcinomas. Thus,
      in the present study, the expression of CD13 and its significance was examined in
      samples of ovarian cancers. The analyses were performed on sections originating
      from 73 tumor samples (43 from primary laparotomies [PL] and 30 from secondary
      cytoreductions [SCRs]). Immunohistochemical reactions were performed on paraffin
      sections of studied tumors, using monoclonal antibodies against CD13. The
      analysis demonstrated no relationships between the expression of CD13 on one hand
      and clinical variables and pathologic variables of the patients on the other
      hand. Expression of CD13 was demonstrated to be significantly more pronounced in
      samples obtained in PLs as compared to samples from SCRs (P < 0.001). Thus, the
      data indicate that a potential treatment of ovarian carcinoma with CD13
      inhibitors should be performed before chemotherapy or in parallel to first-lapse
      chemotherapy.

PMID- 17009974
TI  - Expression of matrix metalloproteinase-26 and tissue inhibitors of
      metalloproteinase-3 and -4 in normal ovary and ovarian carcinoma.
AB  - The objective of this study was to determine the spatial expression of matrix
      metalloproteinases (MMPs) and their physiologic inhibitors, the tissue inhibitor
      of MMP (TIMP)-3 and TIMP-4, in ovarian carcinoma compared to normal ovaries.
      Immunohistochemistry was carried out in this study. Tissue sections prepared from
      normal ovarian tissues from throughout the menstrual cycle (N = 20) and ovarian
      carcinomas (N = 45) characterized as stage I (N = 5), stage III/IV (N = 40) were
      immunostained using polyclonal antibodies to the latent and the active form of
      MMP-26, TIMP-3, and a monoclonal antibody to TIMP-4. Immunoreactive MMP-26, TIMP
      3, and TIMP-4 were detected in all the ovarian cell types in normal and tumor
      tissues. In normal ovarian tissues, theca externa and luteal cells immunostained
      with high intensity for MMP-26 and TIMPs while theca/granulosa cell staining
      intensity increased as lutenization progressed. There was low immunostaining of
      the ovarian stromal and surface epithelial cells for MMP-26, with moderate
      staining for TIMPs. In the carcinoma specimens, cancer cells and vascular
      endothelial cells displayed the highest staining intensity compared to adjacent
      nontumor areas. The immunostaining intensity of MMP-26 and TIMP-3 increased with
      stage of tumor with the invading tumor cells displaying the strongest
      immunostaining. MMP-26, TIMP-3, and TIMP-4 are expressed in normal ovarian as
      well as ovarian tumors with elevated expression in the invasive tumor cells
      suggesting a potential role for MMP-26 in normal ovary and ovarian cancer
      biologic function.

PMID- 17009973
TI  - The prognostic value of endoglin (CD105) expression in ovarian carcinoma.
AB  - Intratumoral angiogenesis has become an important issue after the identification
      of antiangiogenic therapeutics. The purpose of this study was to investigate the
      prognostic value of CD105 in patients with ovarian cancer and also to compare
      with CD31. Fifty-eight patients were included to this study. All the paraffin
      blocks were reviewed, and angiogenesis was determined by immunohistochemical
      staining, using anti-CD105 and anti-CD31 monoclonal antibodies. The mean
      microvessel density (MVD) with CD105 and CD31 were 28.78 +/- 22.20 and 28.69 +/-
      18.57, respectively (P = 0.97). With respect to prognostic factors, CD31 was only
      significant for suboptimal cytoreduction (P = 0.02), and CD105 was significant
      for both advanced stage and suboptimal cytoreduction (P = 0.02 and P = 0.05,
      respectively). For survival analysis, patients were divided into three groups by
      quartiles for each marker (group 1, <25%; group 2, 25-75%; and group 3, >75%). By
      CD31, only significant difference was noted between group 1 and group 2 (P =
      0.03). In analysis with CD105, the survival rate of patients with group 3 was
      significantly worse than group 1 and group 2 (P = 0.01 for both). In multivariate
      analysis, cytoreduction and MVD determined by CD105 remained significant. In this
      study, endoglin was found to be an independent predictor of poor survival.
      Therefore, it could be used for antiangiogenic therapies.

PMID- 17009975
TI  - The distribution and differential risks of human papillomavirus genotypes in
      cervical preinvasive lesions: A Taiwan Cooperative Oncologic Group Study.
AB  - To clarify the distribution and relative risk of different human papillomavirus
      (HPV) genotypes in cervical preinvasive lesions, 1246 women with abnormal
      Papanicolaou smear including atypical squamous cell of unknown significance
      (ASCUS), atypical glandular cell of unknown significance (AGUS), low-grade
      squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial
      lesion (HSIL) were enrolled in a multicenter, cross-sectional study. Colposcopy
      and HPV tests with hybrid capture 2 and polymerase chain reaction-reverse line
      blot were performed. The prevalences of HPV in ASCUS/AGUS-negative histology,
      ASCUS/AGUS, LSIL, HSIL, and invasive cancer were 33.8%, 38.3%, 74.9%, 84.3% and
      100%, respectively, with an overall positive rate of 68.8%. The most common HPV
      types were HPV 16 (18.5%), 52 (16.5%), 58 (13.2%), 33, 51, 53, 18, 39, 59, 66,
      MM8, and 31. In comparing the relative risk of HPV infection in different disease
      status, LSIL and HSIL/carcinoma had a 4.64 (95% CI: 2.98-7.24) and 10.53 (95% CI:
      6.69-16.58) folds of risk of high-risk HPV infection than the negative group. The
      same was true in mixed HPV infection, but not in low-risk type infection. Looking
      into each high-risk HPV type, the relative infection risks for LSIL and
      HSIL/carcinoma, in comparison with the negative group, were 1.67 (0.63-4.43) and
      8.67 (3.46-21.70), 2017 (1.01-4.68) and 3.04 (1.42-6.47), and 1.40 (0.52-3.77)
      and 5.22 (2.07-13.19) for HPV type 16, 52 and 58, respectively. The study
      confirmed the high prevalence and risky nature of HPV 52 and 58 in Taiwanese
      population and conveyed the need to include these HPV types in vaccine
      development.

PMID- 17009976
TI  - Human papillomavirus type 18 and other risk factors for cervical cancer in
      Jakarta, Indonesia.
AB  - Infection with human papillomavirus (HPV) has now been established as a necessary
      cause of cervical cancer. Indonesia is a country with a high cervical cancer
      incidence and with the world's highest prevalence of HPV 18 in cervical cancer.
      No information exists about the prevalence of HPV 18 or other HPV types in the
      Indonesian population. We conducted a hospital-based case-control study in
      Jakarta, Indonesia. A total of 74 cervical carcinoma cases and 209 control women,
      recruited from the gynecological outpatient clinic of the same hospital, were
      included. All women were HPV typed by the line probe assay, and interviews were
      obtained regarding possible risk factors for cervical cancer. HPV was detected in
      95.9% of the cases and in 25.4% of the controls. In the control group, 13.4% was
      infected with a high-risk HPV type. HPV 16 was detected in 35% of the case group
      and in 1.9% of the control group and HPV 18 was identified in 28% of the case
      group and in 2.4% of the control group, suggesting that the oncogenic potentials
      of HPV 16 and HPV 18 in Indonesia are similar. In addition to HPV infection,
      young age at first intercourse, having a history of more than one sexual partner,
      and high parity were significant risk factors for cervical cancer. Within the
      control group, we did not identify determinants of HPV infection. We hypothesize
      that the high prevalence of HPV 18 in cervical cancer in Indonesia is caused by
      the high prevalence of HPV 18 in the Indonesian population.

PMID- 17009977
TI  - Optical coherence tomography as a diagnostic aid to visual inspection and
      colposcopy for preinvasive and invasive cancer of the uterine cervix.
AB  - The purpose of this study was to determine the sensitivity and specificity of
      optical coherence tomography (OCT) under two well-defined clinical settings.
      First, as an aid to cervical cancer screening, using visual inspection with
      acetic acid (VIA) in low-resource settings, and the second, as an adjunct to the
      traditional management of abnormal cervical cytology with colposcopy and biopsy.
      Patients referred for colposcopy with > or = atypical squamous cells of
      undetermined significance were accrued for the study. Each subject underwent VIA
      and colposcopy. OCT was performed in all VIA- and colposcopy-positive areas and
      at the squamocolumnar junction in all four quadrants. The sensitivity of VIA for
      > or = cervical intraepithelial neoplasia 2 was 76% (95% CI 58-88). When OCT was
      applied to VIA as a secondary screen, the specificity improved from 34% (95% CI
      27-41) to 61% (95% CI 60-74). With liberal diagnostic criteria for the majority
      of the colposcopy examinations, OCT showed an even greater relative improvement
      in specificity. OCT proved to be a fair diagnostic modality (receiver operating
      characteristic curve 0.73) adjunctive to VIA and colposcopy. On the basis of the
      above findings, we believe that this technology could potentially show greatest
      utility in the management of cervical dysplasia in low-resource settings where a
      single episode of care is most desirable.

PMID- 17009978
TI  - The use of electrical impedance spectroscopy in the detection of cervical
      intraepithelial neoplasia.
AB  - The objective of this study was to assess the performance of cervical impedance
      spectroscopy in the detection of cervical intraepithelial neoplasia (CIN) using
      the new MKIII impedance probe. A prospective observational study recruited women
      referred to colposcopy with an abnormal Papanicolaou smear. A pencil probe
      incorporating four gold electrodes was used to measure electrical impedance
      spectra from cervical epithelium. Colposcopy examinations, including probe
      positioning, were video recorded to allow for correlation between results
      obtained from colposcopic impression, histopathologic examination of colposcopic
      punch biopsies, and impedance measurements. Cervical impedance-derived parameters
      R, S, R/S, C, and Fc were assessed to see if significant difference in values
      obtained in CIN and normal epithelium existed. The performance of the probe in
      identifying women with CIN was also assessed. One hundred seventy-six women were
      recruited and 1168 points analyzed. Parameters R, S, and Fc showed significant
      separation of CIN or squamous intraepithelial lesion (SIL) from squamous, mature
      metaplastic, and columnar epithelium. Sensitivities of 74% and specificity of 53%
      can be achieved in identifying CIN 2/3 (High-grade SIL) in screened women. We
      conclude that cervical impedance spectrometry provides a potentially promising
      real-time screening tool for CIN with similar sensitivity and specificity to
      currently used screening tests. Further research is ongoing to develop the probe
      for potential clinical use.

PMID- 17009979
TI  - Cervical cancer incidence and survival in Korea: 1993-2002.
AB  - This study examined the incidence rates, histologic and stage distribution, and
      long-term survival rates of patients with cervical cancer in Korea. A total of
      44,182 patients diagnosed with cervical cancer between 1993 and 2002 were
      reported to the Korea Central Cancer Registry and the Gynecologic Oncology
      Committee of Korean Society of Obstetrics and Gynecology. The age-standardized
      incidence rates were 19.0, 17.8, and 15.1 per 100,000 women in 1993-1995, 1996
      1998, and 1999-2002, respectively. The incidence rates of adenocarcinoma (AC)
      have been in the range between 1.2 in 1993-1995 and 1.4 in 1999-2002, while those
      of squamous cell carcinoma declined from 15.1 in 1993-1995 to 12.2 in 1999-2002.
      The 5-year relative survival rate was 79.2%. Relative survival rates, according
      to stage by the FIGO, at 5 years were 94.2%, 69.7%, 38.9%, and 21.1% for stages
      I, II, III, and IV respectively. Relative survivals improved between 1993 and
      1997, probably due to the introduction of cervical cancer screening and effective
      treatment. The incidence rates of AC have been constant despite decreased
      cervical cancer in Korea. Introduction of cervical cancer screening and effective
      treatment may have contributed to the improved relative survival.

PMID- 17009980
TI  - Pattern of failure and long-term morbidity in patients undergoing postoperative
      radiotherapy for cervical cancer.
AB  - The objective of this study was to assess treatment outcomes in a large case
      series of cervical cancer patients undergoing postoperative radiotherapy in a
      single center. Case notes of women referred to the Christie Hospital during 1985
      1997 for postoperative adjuvant radiotherapy for cervical cancer were reviewed.
      Of 478 women eligible for analysis, 282 (58.9%) underwent radical hysterectomy
      and 196 (41.1%) had nonradical hysterectomy. The disease-specific 5-year survival
      for the study population is 70.1%, with a 5-year risk of developing any
      recurrence of 30.5% and a 5-year grade 3 morbidity rate of 3.9%. Survival was
      significantly higher, ie, 80.9% vs 62.7% (P = 0.0001) and recurrence was
      significantly lower, ie, 18.6% vs 38.8% (P < 0.00005) in the group of women who
      had adjuvant radiotherapy following a nonradical hysterectomy compared with
      radical surgery. Thirty percent of women having "radical" surgery had positive
      resection margins and required postoperative adjuvant pelvic radiotherapy. Women
      with node-positive disease, who received adjuvant radiotherapy, had a high rate
      of distant metastases. These women would receive chemoradiotherapy now as primary
      treatment because of the risk of developing distant metastases. If, despite
      staging investigations, surgery reveals node-positive disease, then these women
      should receive adjuvant chemoradiotherapy. Survival was better in women who had
      nonradical surgery due to smaller volume disease when cancers were unsuspected
      and hence will have been cured by surgery alone. Multidisciplinary team working,
      as recommended by national guidelines from 1999, should allow better patient
      selection for treatment.

PMID- 17009981
TI  - Impact of hemoglobin on survival of cervical carcinoma patients treated with
      concurrent chemoradiotherapy is dependent on lymph node metastasis findings by
      magnetic resonance imaging.
AB  - The objective of this study was to confirm whether hemoglobin (Hb) levels during
      chemoradiotherapy are associated with survival in patients with locally advanced
      cervical carcinoma and to assess impact of the Hb level on survival according to
      lymph node (LN) metastasis. A retrospective review of 85 cervical carcinoma
      patients treated with concurrent chemoradiotherapy was conducted. The stage of
      disease ranged between FIGO stage IB and stage IVA. Disease-free and overall
      survivals were evaluated by univariate and multivariate analyses. After median
      follow-up of 35.7 months, 24 patients developed recurrence of disease and 14
      patients died from their disease. Stage, LN metastasis, and squamous cell
      carcinoma antigen and Hb levels during chemoradiation were correlated
      significantly with survival (P < 0.05). Maintenance of Hb above 10.0 g/dL was
      associated with better survival (P < 0.05). However, no such benefits were
      observed in patients with LN metastasis by magnetic resonance imaging (MRI).
      Multivariate Cox regression hazard model showed that Hb levels during
      chemoradiation were an independent prognostic factor in patients without LN
      metastasis by MRI. Maintenance of Hb during chemoradiation is of benefit in
      cervical carcinoma patients without LN metastasis but not with LN metastasis by
      MRI.

PMID- 17009982
TI  - Erythropoietin administration during primary treatment for locally advanced
      cervical carcinoma is associated with poor response to radiation.
AB  - The purpose of this study was to determine whether the use of recombinant
      erythropoietin (r-EPO) during treatment for locally invasive carcinoma of the
      cervix affects recurrence rates, disease-free survival, and overall survival.
      Retrospective analysis of outcomes of patients with locally advanced cervical
      cancer treated with radiation and concurrent chemotherapy between January 1997
      and July 2004 was performed. Recurrence rates, disease-free survival, and overall
      survival were calculated using SPSS statistical software. Throughout P < 0.05 was
      considered significant. Of 68 patients included in this study, 18 patients
      received erythropoietin during treatment and 50 did not. Patient age, stage,
      hemoglobin at presentation, and average weekly hemoglobin (AWH) were similar in
      both groups of patients. The recurrence rate among patients who received r-EPO
      was 61% compared with 30% among patients who did not receive r-EPO (P = 0.014).
      Eight of 18 patients (44%) who received r-EPO were alive at last known follow-up
      compared to 36 of 50 (72%) who did not receive the medication (P = 0.045).
      Disease-free survival and overall survival were significantly shorter in patients
      who received r-EPO during treatment (P = 0.028, 0.032). The administration of r
      EPO during primary treatment of patients with locally advanced cervical cancer is
      associated with increased recurrence rate, increased risk of death due to
      disease, and decreased disease-free and overall survivals.

PMID- 17009983
TI  - Methylation status of the fragile histidine triad and E-cadherin genes in plasma
      of cervical cancer patients.
AB  - Recent evidence suggests that tumor cells may release DNA into the serum and
      plasma of afflicted cancer patients. However, no report existed regarding the
      methylation status of the fragile histidine triad (FHIT) and E-cadherin genes in
      plasma samples of cervical cancer patients. Methylation-specific PCR (MSP) was
      employed to examine CpG island methylation of the FHIT and E-cadherin genes in
      151 pretreatment plasma samples and 30 tumor tissue samples from cervical cancer
      patients. MSP products were cloned and sequenced. CpG island methylation of the
      FHIT and E-cadherin genes was detected in 30.46% and 39.74% of plasma samples,
      respectively, and in 53.33% and 60.0% of tissue samples, respectively. The total
      concordance rate of methylation between plasma samples and tissue samples in FHIT
      gene was 80.00% and that in E-cadherin gene was 76.66%. At least one of the two
      methylated genes was detected in 56.29% of plasma samples and 76.7% of tissue
      samples. The presence of both methylated genes was detected in 13.9% of plasma
      samples and 36.67% of tissue samples. We found that the higher the clinical stage
      and histologic grade, the higher the rate of methylation in both genes in plasma
      samples. CpG island methylation of the FHIT and E-cadherin genes is present in
      plasma of cervical cancer patients. Using the two genes as markers simultaneously
      may allow clinicians to diagnose and evaluate the effect of treatment earlier and
      using fewer invasive procedures.

PMID- 17009984
TI  - Involvement of tumor suppressor in lung cancer 1 gene expression in cervical
      carcinogenesis.
AB  - Tumor suppressor in lung cancer 1 (TSLC1) is a tumor suppressor gene in non-small
      cell lung cancer, and loss of TSLC1 gene expression has been observed in a number
      of epithelial carcinomas and cancer-derived cell lines. We analyzed TSLC1 gene
      expression by real-time reverse transcription-polymerase chain reaction in 39
      invasive cervical carcinomas, 34 cervical intraepithelial neoplasia (CIN) IIIs,
      35 CIN IIs, 32 CIN I, 36 inflammation cervical tissues, and 30 normal cervix
      samples. Loss of TSLC1 gene expression was observed in 30 of 39 (77%) cervical
      carcinomas, 25 of 34 (73%) CIN IIIs, 9 of 35 (26%) CIN IIs, and 7 of 32 (22%) CIN
      Is but was not found in inflammation and normal cervix samples. Compared to
      normal cervical tissue, loss of TSLC1 gene was significantly high in CIN IIIs and
      cervical cancer (P = 0.00). Moreover, loss of TSLC1 gene expression is observed
      at a significantly higher frequency in CIN IIIs and cervical cancers than in CIN
      IIs (P < 0.05). The results show that loss of TSLC1 gene expression is an early
      event in cervical carcinogenesis and often accompanies invasive cervical cancers.

PMID- 17009985
TI  - Implication of human telomerase reverse transcriptase in cervical carcinogenesis
      and cancer recurrence.
AB  - The objective of this study was to evaluate the implication of human telomerase
      reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence.
      One hundred three cases of uterine cervix, including 20 normal, 13 low-grade
      squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial
      lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for
      hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC
      tissues were compared by Fisher exact or Chi-square test. The relationships
      between hTERT and clinicopathologic variables of SCC were also assessed.
      Furthermore, SCC patients were subdivided into negative and positive hTERT
      expression subgroups, and Kaplan-Meier curves were used to plot the cumulative
      recurrence hazard for 5 years. There was a significant difference for hTERT
      expression between LSIL and HSIL subgroups (P < 0.001) but no significant
      difference between normal and LSIL as well as HSIL and SCC subgroups. For SCC
      patients, hTERT expression was positive in lymph nodes, vagina, and parametrium
      metastastic cases. However, it did not reach a significant difference. The
      cumulative recurrence hazard for 5 years was about 29% in positive hTERT
      expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In
      conclusion, a point stage of HSIL exists in the progression of cervical
      carcinogenesis when the hTERT expression increases significantly. Moreover, SCC
      patients with positive hTERT expression may have higher cumulative recurrence
      hazard.

PMID- 17009986
TI  - Lymph node size in uterine cancer: A revisit.
AB  - To study whether lymph node size is a good predictor of lymph node metastasis in
      uterine cancer, we reviewed the pathologic sections of pelvic and para-aortic
      lymph node removed from uterine cancer patients who underwent surgical staging in
      our institution from January 1994 to December 2004. The long axis of each
      individual node was measured. Out of 4280 total nodes obtained (178 cases), 86
      nodes (28 cases) were positive for metastatic cancer (2.0% of total nodes or
      15.7% of cases). Among the positive nodes, 11 nodes (12.8%) had nodal long axis
      <5 mm, 34 nodes (39.5%) had long axis of 5-9 mm, and 32 (37.2%) and 9 nodes
      (10.5%) had long axes of 10-19 mm and >20 mm, respectively. More than half
      (52.3%) of these positive nodal long axes were less than 10 mm. At lymph node
      size of 10 mm that was the common point of reference for pathologic enlargement,
      the sensitivity, specificity, negative and positive predictive value of lymph
      node to predict metastatic cancer were 47.7%, 76.7%, 98.6%, and 4.0%,
      respectively. From these findings, we tended to conclude that lymph node size is
      not a good predictor of lymph node metastasis in uterine cancer.

PMID- 17009987
TI  - Role of lymphadenectomy and pelvic radiotherapy in patients with clinical FIGO
      stage I endometrial adenocarcinoma: An analysis of 208 patients.
AB  - Two hundred and eight patients with a clinical stage I endometrial carcinoma were
      studied (164 fulfilled the inclusion criteria). High risk was defined as
      nonendometrioid, or endometrioid tumors grade 3 (G3), or G2 with any or G1 with
      deep (>1/2) myometrial infiltration. The low-risk group consisted of the
      remaining patients. Surgical staging in the high-risk group included pelvic
      lymphadenectomy with para-aortic lymphadenectomy in selected cases. Twelve
      percent of the high-risk patients had nodal metastasis. Patients with low-risk
      (group A, n = 85) and high-risk disease confined to the uterus (group B, n = 57)
      did not receive adjuvant radiotherapy. Patients with nodal metastases (group C, n
      = 10) received postoperative irradiation. The total recurrence rate of the entire
      population was 12.5%, and the actuarial overall survival, disease-specific
      survival, and disease-free survival were 90%, 94%, and 88%, respectively. All
      patients with only vaginal relapse (n = 9) were cured locally with salvage
      radiotherapy until the date of analysis. The pelvic relapse rate was low as only
      one patient of group B recurred in the pelvis. In conclusion, lymphadenectomy
      remains indicated to better select patients at high risk of pelvic recurrence
      that may benefit from postoperative radiotherapy.

PMID- 17009988
TI  - Uterine metastasis from hepatocellular carcinoma: A case report.
AB  - The extrahepatic spread of hepatocellular carcinoma (HCC) is uncommon. Moreover,
      metastatic uterine tumor from extragenital primaries is rare. We report a 63-year
      old woman with uterine metastasis from HCC. She had undergone transcatheter
      arterial embolization four times and surgery for HCC from 2-4 years before. This
      time, she underwent resection of a newborn, head-sized uterine tumor that was
      proven to be metastasis from HCC. This is the first described case of metastatic
      uterine tumor originated from HCC.

PMID- 17009989
TI  - HER-2/neu overexpression in uterine papillary serous cancers and its possible
      therapeutic implications.
AB  - Uterine papillary serous carcinoma (UPSC) is a highly aggressive variant of
      endometrial cancer with features similar to high-grade ovarian cancer. Patients
      tend to be elderly, thin, have a high grade tumor with extensive extrauterine
      disease at the time of diagnosis. The transmembrane receptor encoded by the HER-2
      cellular oncogene is amplified in several types of human carcinomas and provides
      an attractive therapeutic target. HER-2/neu, the transmembrane receptor encoded
      by the c-erbB2 gene, is overexpressed by immunohistochemistry in <25% of ovarian
      cancers and 20-30% of breast cancers, and <10% of endometrial cancer. There are
      prognostic and therapeutic implications associated with the overexpression of
      this transmembrane protein. Herceptin, a humanized murine monoclonal antibody
      directed against the extracellular domain of the HER-2/neu protein, is being used
      to treat breast cancer that overexpresses HER-2/neu. We reviewed all patients
      diagnosed with UPSC between 1999-2001. Twenty-six patients were identified, and
      19 patients had specimens available for evaluation. We performed
      immunohistochemical analysis (Herceptest, Dako, Carpinteria, CA) on 19 paraffin
      embedded blocks of UPSC tumors looking for HER-2/neu over expression. Five out of
      19 (26%) stained heavily (3+) for HER-2/neu receptor protein. Four of these five
      patients had advanced disease at diagnosis. Two of these patients were
      subsequently treated with Herceptin; one with complete response and one with
      stable disease based on CT scan and CA-125 findings. Targeting HER-2/neu may be
      beneficial for a select group of patients with UPSC. We are continuing to
      evaluate samples for HER-2/neu over expression by fluorescence in situ
      hybridization (FISH).

PMID- 17009990
TI  - Immunohistochemical characterization of cancer antigen in uterine cancers.
AB  - The pattern of cancer antigen (CA-125) expression by immunohistochemistry (IHC)
      was investigated in malignant and nonneoplastic endometrium in endometrial
      carcinoma. Ninety cases of primary uterine carcinomas (65 endometrioid [EM]
      carcinoma, 15 serous papillary [SP] carcinoma, 6 carcinosarcomas [malignant mixed
      mullerian tumors], and 4 clear cell carcinoma [CC]) and adjacent atrophic and/or
      hyperplastic endometrium were analyzed by IHC for CA-125 expression. The
      percentage and intensity of luminal, apical, basal, and diffuse cytoplasmic
      immunostaining of epithelial cells were categorized on a scale of 0-4. The
      immunoreaction score (IRS score) was calculated and correlated with the grade and
      stage of carcinoma according to the histologic type. CA-125 expression (3-4/4)
      was localized in apical borders of grade 1 and grade 2 EM carcinoma and was weak
      or negative (0-1/4) in grade 3 EM. Mucinous differentiation in EM was associated
      with intense luminal and apical staining. Squamous areas and stroma showed no
      staining at all. SP carcinoma and endometrial intraepithelial carcinoma showed
      much higher mean IRS score than EM. In malignant mixed mullerian tumors (MMMT),
      the epithelial component stained as above according to the type of epithelial
      cell differentiation of the neoplastic cells. Benign proliferative glands showed
      moderate apical luminal, basal, and cytoplasmic staining. Intense diffuse
      staining was observed in atypical complex hyperplasia. Different patterns of CA
      125 immunostaining were observed in normal, hyperplastic, and neoplastic
      endometrium. IRS score correlated with the grade but not with the stage of EM
      carcinoma. The intense different staining pattern of endometrium with atypical
      complex hyperplasia suggests that CA-125 may be a useful diagnostic aid.

PMID- 17009991
TI  - Endometrial tumor invasiveness is related to metalloproteinase 2 and tissue
      inhibitor of metalloproteinase 2 expressions.
AB  - Matrix metalloproteinase (MMPs) expression has been linked to gynecological tumor
      aggressiveness. The objective of this study was to determine MMP-2, MMP-7, and
      MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 expression
      in endometrial malignancies and their relation to clinical and histologic
      parameters. Formalin-fixed, paraffin-embedded tumor samples from 50 patients with
      endometrial carcinoma treated between 1999 and 2004 were stained with specific
      monoclonal antibodies. The tumors were grouped according to the FIGO
      classification. The staining results were compared to histologic and clinical
      data. Semiquantitative analysis of MMP and TIMP expression showed a significant
      difference in TIMP-2 expression according to the histologic subtype (P = 0.03)
      and also a trend towards a difference in MMP-9 expression (P = 0.05). MMP-2
      expression increased and TIMP-2 expression fell as the histologic grade increased
      (P = 0.0007, P < 0.0001, respectively). MMP-2 expression correlated with lymph
      node metastasis (P = 0.04), while TIMP-2 expression correlated with the depth of
      myometrial invasion (P = 0.01), vasculolymphatic space involvement (P = 0.02),
      and lymph node metastasis (P = 0.0003). These results support the involvement of
      MMPs and TIMPs in endometrial tumor growth and progression. High MMP-2 and low
      TIMP-2 expression were the most potent markers of endometrial tumors with a high
      risk of local and distant spread.

PMID- 17009992
TI  - Estrogen and progesterone receptors and telomerase enzyme immunohistochemical
      detection in gestational trophoblastic tumors.
AB  - The purpose of this study is to evaluate the immunohistochemical detection of
      telomerase enzyme and estrogen receptor (ER) and progesterone receptor (PGR) in
      gestational trophoblastic neoplasia (GTN) and its clinical significance. Formalin
      fixed paraffin blocks for 30 patients (24 with molar pregnancy, 3 with
      choriocarcinoma, and 3 with placental site trophoblastic tumor) as cases and six
      products of conception samples from patients with incomplete abortion as controls
      were included in the study. Immunohistochemical detection of the telomerase
      catalytic protein and ER and PGR was carried out using streptavidin-biotin
      peroxidase method. All control tissues were negative for telomerase and ER
      expression, while five of six were PGR positive. Significant positive telomerase
      expression was detected in all gestational trophoblastic tumors (three of six
      partial moles, 12 of 18 complete moles, three of three choriocarcinomas, and two
      of three placental site trophoblastic tumors). Nine of 24 molar pregnancies were
      followed by GTN. Molar pregnancies followed by GTN were associated with higher
      serum beta-hCG (human chorionic gonadotrophic hormone), larger uterine size for
      gestational age, negative ER expression, negative PGR expression, and positive
      telomerase expression. All patients with molar pregnancy with negative telomerase
      expression (9 of 24) showed spontaneous regression after evacuation. Positive
      telomerase expression and its immunohistochemical detection are associated with
      the development of GTN. Negative telomerase expression is highly predictive of
      postmolar spontaneous regression. Patients with molar pregnancies with negative
      telomerase expression can be saved the long-term follow-up. ER and PGR expression
      do not show a significantly different pattern in molar tissues, while negative
      expression is associated with developing GTN. Cautions on the use of postmolar
      hormonal contraception may be unjustified.

PMID- 17009993
TI  - Laparoscopically assisted radical vaginal hysterectomy (Coelio-Schauta): A
      comparison with open Wertheim/Meigs hysterectomy.
AB  - The objective of this study was to compare the safety, efficacy, and short-term
      benefits of the Coelio-Schauta procedure with open Wertheim/Meigs radical
      abdominal hysterectomy. We retrospectively analyzed records of our first 35
      consecutive patients undergoing laparoscopically assisted radical vaginal
      hysterectomy (LARVH) for early cervical cancer and 32 consecutive patients of
      open radical hysterectomy (ORH) performed between 1999 and 2005 in our
      institution. We analyzed patient age, bodyweight, previous abdominal surgery,
      operating time, blood loss, perioperative complications, postoperative bladder
      dysfunction, other postoperative complications, and histologic type. The FIGO
      stage, excision margins, node count and node status, follow-up, and recurrence
      rates were also taken into account. We excluded stage IA and stage II disease
      patients to reduce the impact of tumor size on the outcome of the surgery. This
      left 27 patients with stage IIB disease who had LARVH and 28 patients with stage
      IB disease who had ORH. These patients formed the study group. The cohorts were
      similar in age, bodyweight, previous abdominal surgery, histologic subtype, FIGO
      stage, resection margins, node count and node status, length of follow-up, and
      recurrence. There were statistically significant differences between LARVH and
      ORH for duration of surgery (mean 160 vs 132 min), intraoperative blood loss (479
      vs 715 mL), hospital stay (mean 5 vs 9.3 days), postoperative complications (6 vs
      20 patients), and duration of bladder catheterization (mean 4.4 vs 8.8 days).
      Four LARVH patients and no ORH patients had urinary tract injury that was
      repaired. None had long-term sequelae. Our data confirm that LARVH is a suitable
      alternative to ORH hysterectomy for small-volume stage IB1 cervical cancer with
      similar clinical efficacy and a superior postoperative recovery and postoperative
      morbidity profile. Urinary tract trauma is a clear risk in the early stages of
      the learning curve.

PMID- 17009994
TI  - Laparoscopic splenectomy for isolated parenchymal splenic metastasis of ovarian
      cancer.
AB  - Metastatic carcinoma of the spleen occurs in a setting of widespread malignant
      disease. Solitary parenchymal splenic metastasis of ovarian carcinoma is rare. We
      report a case of a 59-year-old woman who presented with an elevated serum CA125
      level due to a solitary splenic metastasis after a long disease-free period. She
      was treated with laparoscopic splenectomy followed by chemotherapy. The
      literature contains 16 cases of solitary parenchymal splenic metastasis of
      ovarian carcinoma. Our case is the third case that was treated with laparoscopic
      splenectomy. We review the literature, and we focus on the laparoscopic approach
      in managing these cases.

PMID- 17009995
TI  - Severe prolonged gastroparesis after cytoreductive surgery in an advanced ovarian
      cancer patient.
AB  - Number and type of complications after ovarian cancer surgery can vary greatly
      according to both the patient's characteristics, and the extension and type of
      surgery. Current literature lacks in mentioning specific gastrointestinal side
      effects, which could be evidenced during the early postoperative course of
      patients submitted to major gynecological oncologic surgery. A severe
      gastroparesis prolonged for 2 months after cytoreductive surgery in an advanced
      ovarian cancer patient was successfully treated with conservative multidrug
      therapy. Gastroparesis has to be enumerated as a rare but possible event after
      major gynecological oncologic surgery. A conservative management involving
      decompressive nasogastric tube, nutritional support, antiemetic drugs, prokinetic
      drugs is suggested, while surgical therapy is only recommended in a very small
      subset of unmanageable patients.

PMID- 17009996
TI  - A substantial part of the fallopian tube is left after standard prophylactic
      bilateral salpingo-oophorectomy.
AB  - Women with a deleterious germline mutation in BRCA1 or BRCA2 are candidates for
      bilateral salpingo-oophorectomy (BSO). To address the need for adjustment of the
      current BSO procedure, we investigated the length and the nature of the fallopian
      tube epithelium that is not removed by BSO. Fourteen consecutive hysterectomy
      specimens were collected. Complete cross-sections with a 3-mm interval were made
      of the tubal lumen from the outside of the uterus at the cutoff point of the
      current BSO procedure to the uterine cavity and examined for the presence or
      absence of tubal type (ciliated) epithelium and subepithelial endometrial stroma.
      The fallopian tube remnant had a median length of 12 mm (range 6-15 mm). Tubal
      type (ciliated) epithelium was shown to be present in all uteri in the first
      cross-section containing 100% endometrial stroma, as well as in the uterine
      cavity of all but two of the hysterectomy specimens. A substantial part of the
      fallopian tube remains in situ after prophylactic BSO and is covered with tubal
      type ciliated epithelium. More research is necessary to investigate the role of
      this remnant part of the tube for BRCA carriers.

PMID- 17009997
TI  - Recurrent small cell carcinoma of the ovary treated with docetaxel: A case
      report.
AB  - Multiagent chemotherapy for small cell carcinoma of the ovary (SCCO) may
      contribute to the prolonged survival of young women who are suffering from this
      disease, even in the advanced stage with remaining tumor, although the rarity of
      SCCO complicates the generalization of chemotherapy agents and operation methods
      for this disease. A 24-year-old patient with SCCO FIGO stage IIC is alive after
      recurrences and chemotherapy including cisplatin + etoposide after the first
      operation and docetaxel for the second recurrence. She is now doing well with no
      evidence of disease more than 4 years after the first operation and 2 years after
      docetaxel treatment. This may be the first report describing the use of docetaxel
      that may be included in multiagent chemotherapy.

PMID- 17009998
TI  - Triple simultaneous primary gynecological malignancies in a 56-year-old patient.
AB  - The occurrence of double simultaneous primary cancers is common. However, the
      occurrence of synchronous primary triple gynecological malignancies is an
      extremely rare event. In this report, the clinical and pathologic findings of a
      56-year-old female patient with synchronous triple primary gynecological cancers
      including well-differentiated ovarian mucinous cystadenocarcinoma, well
      differentiated endometrial endometrioid adenocarcinoma, and uterine
      leiomyosarcoma were presented. Synchronous primary, well-differentiated
      endometrial endometrioid adenocarcinoma and leiomyosarcoma of uterus without any
      ovarian neoplasm has only been once described in the English literature. To our
      knowledge, the presented patient is the first case in aspect of accompanying
      ovarian mucinous adenocarcinoma to endometrial endometrioid adenocarcinoma and
      leiomyosarcoma of uterus.

PMID- 17009999
TI  - Methodology in plasma proteomic pattern experiments.

PMID- 17010001
TI  - Use of adjuvant groin irradiation in 20 patients with unilateral inguinal node
      positive vulval carcinoma.

PMID- 17010002
TI  - Safety of supracostal punctures for percutaneous renal surgery.
AB  - AIM: Supracostal superior calyceal access has been shown to be the most suitable
      approach for staghorn calculi, calculi in the upper ureter and complex inferior
      calyceal calculi, as well as for antegrade endopyelotomy. However, many
      urologists hesitate in using this approach because of the potential for chest
      complications. The aim of this study was to analyze one institution's data
      regarding the safety and efficacy of this approach for percutaneous renal
      surgery. METHODS: A total of 890 renal units (762 patients) were treated with
      percutaneous renal surgery (849 percutaneous nephrolithotomy, 41 antegrade
      endopyelotomy) from July 1998 to July 2004. Supracostal access was obtained in
      332 (37.3%) patients. The indications for a supracostal approach were
      ureteropelvic junction obstruction, staghorn and complex inferior calyceal
      calculi, and stones in the upper calyx or the upper ureter. All punctures were
      made by the urologist under C-arm fluoroscopic guidance in the prone position.
      RESULTS: The interspace between 11th and 12th rib was used in all except four
      patients in whom the puncture was made above the 11th rib. Eleven patients
      (3.31%) had a pleural breach presenting with fluid in the chest. Insertion of a
      chest tube was required in seven patients, while other four were managed
      conservatively. No patient had injury to the lung or other viscera. Hospital stay
      was not significantly prolonged as a result of the pleural breach in any patient.
      Except for staghorn calculi where multiple tracts were a necessity for maximal
      clearance, a single supracostal superior or middle posterior calyceal access
      served the purpose in 86% (177/205) of patients who underwent percutaneous
      surgery for renal or upper ureteric calculi. CONCLUSIONS: The supracostal
      superior calyceal approach was found to be effective as well as safe, with an
      acceptably low risk of chest complications.

PMID- 17010003
TI  - Urological complications in 980 consecutive patients with renal transplantation.
AB  - AIM: To present the urological complications of renal transplantations performed
      in the last 14 years at one center and to briefly explain a modified method of
      Lich-Gregoir ureteroneocystostomy. METHODS: The data of 980 patients receiving
      kidney transplants at the authors' institution from April 1991 to February 2004
      were reviewed in a retrospective prospective study. In particular, surgical
      techniques and urological complications were noted. RESULTS: A total of 980
      patients had received kidney transplantation. Extravesical ureteroneocystostomy
      (Lich-Gregoir method) was used in the first 480 patients (group A). In the
      subsequent 500 patients, the authors' modified method of extravesical
      ureteroneocystostomy, using single layer anastomosis and small feeding tubes as
      stent, was used (group B). Overall urological complication rate was 2.8% (28
      patients), including leakage (13 patients, 1.3%), stenosis (seven, 0.7%),
      obstruction (one, 0.1%), distal ureter necrosis (four, 0.4%), pelvocalyceal
      fistula (two, 0.2%) and implantation of ureter into the peritoneum (one, 0.1%).
      Urological complications were significantly more common in group A compared to
      group B (16, 3.3% and 9, 1.8%, respectively; P < 0.05). CONCLUSIONS: Preserving
      the adventitia, fat and blood supply of the ureter by delicate dissection of the
      ureter during donor nephrectomy, short ureters, and fixation of the adventitia,
      fat and blood supply of the ureter to the bladder wall, to prevent kinking or
      twisting, are important factors in decreasing urological complications.
      Additionally, the authors' method of ureteroneocystostomy is also effective in
      decreasing the incidence of ureteric complications.

PMID- 17010004
TI  - How many uncomplicated male and female overactive bladder patients reveal
      detrusor overactivity during urodynamic study?
AB  - OBJECTIVE: We retrospectively evaluated the incidence of detrusor overactivity
      (DO) in uncomplicated overactive bladder syndrome (OAB) patients. METHODS: From
      December 1993 to October 2003, 139 adult patients were referred to an urodynamic
      clinic for urodynamic evaluation of frequency and/or urinary incontinence. Of
      these, 50 patients (12 males and 38 females) with urgency, without any overt
      pathological conditions, were retrospectively evaluated in regard to patient age,
      storage symptoms, urodynamic parameters, and the presence or absence of DO (DO
      patients or no DO patients, respectively). RESULTS: The overall incidence of DO
      was 75% (nine of 12 patients) and 36.8% (14 of 38 patients) in male and female
      patients, respectively. Two of nine male DO patients and five of 14 female DO
      patients revealed DO after provocative maneuvers. In male patients, all DO
      patients were OAB wet. In female patients, 13 of 14 DO patients were OAB wet
      (92.9%), whereas 17 of 24 no DO patients were also OAB wet (70.8%). Compared with
      no DO patients, female DO patients revealed statistically significant lower
      maximum cystometric capacity (P = 0.0139) and lower vesical compliance (P =
      0.0002). Although aged 60 years or more was associated with DO in univariate
      analysis in female patients, any symptoms, even incontinence, were not associated
      with DO in both sexes. CONCLUSION: It is supposed that, in contrast to male OAB,
      DO might not be a major underlying cause of uncomplicated female OAB.

PMID- 17010005
TI  - Naftopidil monotherapy vs naftopidil and an anticholinergic agent combined
      therapy for storage symptoms associated with benign prostatic hyperplasia: A
      prospective randomized controlled study.
AB  - AIM: The aim of this study was to compare the efficacy and safety of alpha1
      adrenoceptor (alpha1-AR) antagonist monotherapy with combination therapy using
      alpha1-AR antagonist and anticholinergic agent for benign prostatic hyperplasia
      (BPH) with storage symptoms as the chief complaint. METHODS: In this prospective
      comparative study, either 25-75 mg/day of naftopidil monotherapy (monotherapy
      group) or combination therapy using 25-75 mg/day of naftopidil and an
      anticholinergic agent (10-20 mg/day of propiverine hydrochloride or 2-6 mg/day of
      oxybutynin hydrochloride; cotherapy group) were administered for 12 weeks to 101
      BPH patients with storage symptoms. RESULTS: International prostate symptom score
      (IPSS) and quality of life (QOL) index improved significantly in both groups,
      with no marked differences between groups. Maximum flow rate (Qmax) and residual
      urine volume (RUV) tended to improve in both groups, again with no marked
      differences between groups. However, median post-therapeutic RUV was
      significantly worse for the cotherapy group (45.0 mL) than for the monotherapy
      group (13.5 mL; P = 0.0210). Ratio of patients with increased RUV was also
      significantly worse for cotherapy (22.9%) than for monotherapy (5.0%; P = 0.038).
      CONCLUSIONS: Although the anticholinergic dosage was low, the present results
      suggest that naftopidil monotherapy was as useful as combination therapy of
      naftopidil and an anticholinergic agent. Therefore, naftopidil is a useful agent
      as the first choice in BPH patients with storage symptoms.

PMID- 17010006
TI  - Prevalence of prostatitis-like symptoms in Japanese men: Population-based study
      in a town in Hokkaido.
AB  - AIM: To determine the prevalence of prostatitis-like symptoms in Japanese men
      living in one town. METHODS: A cross-sectional and population-based study was
      performed in a town that had 6385 men aged from 20 to 79 years. We sent two
      questionnaires, the validated Japanese version of the National Institutes of
      Health Chronic Prostatitis Symptom Index and the International Prostate Symptom
      Score (I-PSS) with questions about individual medical information, to 1424
      randomly selected community-indwelling men. Subjects were defined as having
      prostatitis-like symptoms if they complained of perineal and/or ejaculatory pain
      or discomfort and their total pain score was four or greater. RESULTS: A total of
      512 men (36%) responded completely to the questionnaires. Of the 512 responders,
      25 men (4.9%) were identified as having prostatitis-like symptoms. Prevalence of
      symptoms was the same in men aged younger than 50 years (5.0%) as those 50 years
      and older (4.8%). The I-PSS score was 10.8 in men with prostatitis-like symptoms,
      which was higher than in those without symptoms. CONCLUSIONS: Prevalence of
      prostatitis-like symptoms was 4.9% in randomly selected men. International
      comparison of prevalence of the symptoms may contribute to further understanding
      of chronic prostatitis.

PMID- 17010007
TI  - Computer simulated additional deep apical biopsy enhances cancer detection in
      palpably benign prostate gland.
AB  - OBJECTIVES: The objective of this study was to use computer simulation to
      investigate the optimal biopsy scheme for enhancing the detection of cancer in
      palpably benign prostate glands. METHODS: The predominant distribution of
      palpably benign prostate cancer is anterior apex to mid-prostate. We used
      computer simulation to optimize apical samplings and to simulate the biopsy
      procedure, including angle and length. A total of 254 consecutive patients with
      palpably benign prostate glands underwent sextant biopsy plus two additional deep
      apical biopsies. RESULTS: Based on the computer simulation, lateral sextant and
      two additional medially located deep apical cores with a sagittal penetration
      angle of 80 degrees had the maximum cancer detection. Of the 254 patients, 58
      (22.8%) had prostate cancer: 28 (48.3%) were positive only at the standard
      sextant sites, 12 (20.7%) were positive exclusively at the deep apical sites, and
      the remaining 18 (31.0%) were positive at both sites. Patients with gray-zone
      prostate-specific antigen (PSA) ranges of 4.1-10.0 ng/mL had increased cancer
      detection rates of 24% compared to sextant biopsy. Enhanced cancer detection by
      the deep apical biopsy was also evident in patients with a prostatic volume >40
      cm3 (by 36.4%) and PSA 2.1-4.0 ng/mL (by 13.3%). CONCLUSIONS: Using a computer
      simulation-based biopsy scheme with deep apical sampling cores enhanced the
      detection of prostate cancer in palpably benign glands, especially in men with
      PSA ranges of 4.1-10.0 ng/mL or a gland volume of >40 cm3. Our approach with
      fewer sampling cores may have been more cost-effective than other extensive
      biopsy schemes, but further studies with larger samples are warranted.

PMID- 17010008
TI  - Evaluation of a prostate biopsy strategy for cancer detection using a computer
      simulation system with virtual needle biopsy for three-dimensional prostate
      models.
AB  - AIM: We evaluated a prostate biopsy strategy for cancer detection using a
      computer simulation system with virtual needle biopsy for three-dimensional (3D)
      prostate models. METHODS: Two 3D prostate models with a volume of 25 cc or 50 cc
      were constructed from computed tomographic images of radical prostatectomy
      specimens. The peripheral zone (PZ) and transition zone (TZ) were arranged in the
      prostate models according to the anatomical information. Four thousand patterns
      of cancer lesions were automatically inserted into each prostate model with a
      proportion of 75% in PZ and 25% in TZ. Average hit rates (AHR) in prostate models
      were evaluated both with an increased number of biopsy cores and various angles
      of virtual needle biopsy. The influence of adding secondary tumors for hit rates
      was also evaluated. RESULTS: For both sizes, the laterally angled biopsy in 4-8
      core biopsy schemes showed higher AHR than the vertical plane biopsy, while the
      vertical plane biopsy in 10-18 core biopsy schemes showed higher AHR than the
      laterally angled biopsy. A higher number of biopsy cores increased the AHR of
      secondary tumors. CONCLUSIONS: Our results suggest that it is important in
      prostate cancer detection to change the needle placement according to the number
      of biopsy cores and the size of the prostate.

PMID- 17010009
TI  - Depression and lower urinary tract symptoms: Two important correlates of erectile
      dysfunction in middle-aged men in Hong Kong, China.
AB  - AIM: To evaluate the correlates of erectile dysfunction (ED) in Hong Kong middle
      aged Chinese men aged 45-64 years. METHODS: A community-based cross-sectional
      household survey was performed in Hong Kong. The Chinese abridged version of the
      International Index of Erectile Function (IIEF-5) was used to measure erectile
      function. The International Prostate Symptom Score (IPSS) was used to measure
      lower urinary tract symptoms (LUTS) and depressive symptoms were measured by the
      Center for Epidemiological Studies Depression Scale (CES-D). Demographic and
      lifestyle data were also collected. The association between ED and its correlates
      was analyzed using bivariate and multivariate analyses. RESULTS: Of the 545
      subjects who agreed to participate in the survey, 75 refused to answer questions
      about their sexual activities and function. Out of those who responded, 118 (22%)
      subjects were not sexually active (not sexually active over the past 4 weeks).
      Out of 352 subjects, 60.3% suffered from some degree of ED. Age, presence of
      depression defined by CES-D and moderate LUTS were associated with increased odds
      of having ED. In multivariate analysis, depressive symptoms identified by CES-D
      (OR = 2.3, CI: 1.2-4.6) and moderate LUTS (OR = 3.7, CI: 1.6-8.3) were
      independently associated with increased odds of having ED. CONCLUSION: ED is an
      important public health problem in Chinese middle-aged men, with more than half
      suffering from some degree of ED. Depression and LUTS were significant and
      important risk factors associated with ED.

PMID- 17010010
TI  - Ejaculatory disorder caused by alpha-1 adrenoceptor antagonists is not retrograde
      ejaculation but a loss of seminal emission.
AB  - AIM: The etiology of the ejaculatory disorder induced by alpha-1 blockers is
      still controversial, although it has been suggested to be retrograde ejaculation.
      The aim of this study was to investigate the distribution of alpha-1 adrenoceptor
      subtype mRNA in human seminal vesicles, and to analyze the prevalence and
      etiology of the disorder in healthy men. METHODS: Experimental Study. Seminal
      vesicles from 10 surgical specimens (eight radical prostatectomy, two radical
      cystectomy) were dissected. Real-time PCR was conducted for quantification of
      mRNA expression of each alpha-1 adrenoceptor subtype. Clinical Study. Ejaculatory
      disorder was investigated using 17 healthy male volunteers. Tamsulosin (0.2 mg
      and 0.4 mg) and naftopidil (50 mg and 100 mg) were administered in a crossover
      manner for 3 days. The ejaculatory volume, sperm count in midstream urine after
      ejaculation, and fructose concentration in seminal plasma were investigated.
      RESULTS: Real-time PCR revealed that alpha-1a mRNA was significantly predominant
      in seminal vesicles (P < 0.001; 1a, 75.0%; 1b, 11.7%; 1d, 13.3%). Ejaculatory
      volume (baseline 2.72 +/- 0.28 mL) significantly decreased in the tamsulosin
      group (0.2 mg, 1.75 +/- 0.31 mL; 0.4 mg, 1.51 +/- 0.39 mL; P < 0.05), but not in
      the naftopidil group (50 mg, 2.70 +/- 0.24 mL; 100 mg, 2.48 +/- 0.26 mL; P = NS).
      There was no sperm in midstream urine after any ejaculation. CONCLUSIONS: The
      current study demonstrates that alpha-1a mRNA is predominant among the
      adrenoceptor subtypes in human seminal vesicles. Decreased capacity of
      contraction of the seminal vesicles is proposed as the cause of the ejaculatory
      disorder induced by alpha-1 blockers.

PMID- 17010011
TI  - Posterior urethral valve: Outcome of antenatal intervention.
AB  - INTRODUCTION AND AIM: Antenatal treatment of obstructive uropathy, although
      widely performed, remains controversial. This study evaluated the long-term
      outcome of managing patients with posterior urethral valves (PUV), highlighting
      the effect of antenatal vesicoamniotic shunt placement for patients who underwent
      fetal surgery. METHODS: The medical records of 58 patients with PUV were
      retrospectively reviewed from June 1998 to June 2004. On the basis of prenatal
      assessment of sonographic findings and serial urinary electrolytes and protein
      measurements, patients were divided into two groups: group 1 comprised patients
      who had antenatal vesicoamniotic shunt placement whereas group 2 comprised
      patients who underwent postnatal surgical correction of PUV. Their outcomes and
      long-term results were evaluated. RESULTS: Patients were followed up from 6
      months to 6(1/2) years (mean 3.9 years). Group 1 included 12 patients who had
      vesicoamniotic shunt placement and were confirmed postnatally to have PUV. Four
      patients out of 12 died (33.3%); three out of the eight living patients had
      perinatal complications. Of the eight living patients, three (37.5%) underwent
      valve ablation and five (62.5%) underwent urinary diversion (three vesicostomies
      and two cutaneous ureterostomies). Renal function returned to normal in only four
      patients (50%). Radiological abnormalities (hydronephrosis and/or reflux)
      resolved in three (37.5%) patients, was downgraded in one (12.5%) patient and
      persisted in four patients (50%). Group 2 included 46 patients who were treated
      postnatally. Thirty-five patients (76%) underwent primary valve ablation, while
      11 (24%) underwent urinary diversion (seven vesicostomies, four cutaneous
      ureterostomy and one pyelostomy). Renal function returned to normal in all
      patients who underwent valve ablation, except in three, while renal function
      returned to normal in only three of 11 patients who underwent urinary diversion.
      Radiological hydronephrosis and/or reflux resolved in 28 patients (60.9%), was
      downgraded in six patients (13%) and persisted in 12 patients (26.1%).
      CONCLUSIONS: Antenatal vesicoamniotic shunt placement makes no difference to the
      outcome and long-term results of patients with PUV and debate about its efficacy
      on renal outcome remains. Primary valve ablation is the keystone of treatment for
      patients with PUV that might achieve the primary goal of nephron preservation.
      The lowest creatinine concentration in the first year of life is the most
      appropriate predictor of future renal function.

PMID- 17010012
TI  - Sexuality and seeking medical help for erectile dysfunction in young adults with
      spina bifida.
AB  - OBJECTIVES: The objectives of this study were to evaluate the correlation between
      the sexual function of spina bifida (SB) patients and Sharrard classification,
      touch sensation on the penis, to examine if SB patients who are sexually active
      have erectile dysfunction (ED) on the International Index of Erectile Function-5
      (IIEF5), and to clarify if they seek medical treatment for ED. METHODS: Thirty
      six male SB patients aged over 18 years were enrolled. A questionnaire was sent
      to all patients that included the following items: touch sensation on the penis,
      psychogenic erection, rigidity at erection, ejaculation, orgasm and experience in
      sexual intercourse. In addition, patients who had experience in sexual
      intercourse were asked about ED through the use of the IIEF5 and whether or not
      they sought medical help for their ED. RESULTS: Twenty-six patients responded.
      The positive rates of psychogenic erection, rigidity at erection, ejaculation and
      orgasm were 85%, 54%, 88% and 65% respectively. Psychogenic erection and
      ejaculation correlated with Sharrard classification. Rigidity at erection and
      orgasm correlated with touch sensation on the penis. Eleven patients had
      experience in sexual intercourse and six of them were diagnosed as having ED on
      the IIEF5. There were no factors correlating with ED. None of the patients sought
      medical advice and none was treated for ED. CONCLUSIONS: Sexual function of SB
      patients could be predicted by Sharrard classification and touch sensation on the
      penis to some degree. However, ED did not correlate with sexual function.
      Therefore, we should not evaluate the neurological loss but instead provide
      adequate information.

PMID- 17010013
TI  - Renal damage in rats induced by myocardial ischemia/reperfusion: Role of nitric
      oxide.
AB  - BACKGROUND: It has been demonstrated that myocardial ischemia/reperfusion (MI/R)
      causes renal damage. However, the mechanism underlying this damage in kidneys
      during revascularization of myocardium is unclear. Direct renal
      ischemia/reperfusion has been implicated in the induction of inducible nitric
      oxide synthase (iNOS) that leads to increase production of nitric oxide (NO).
      Recently, excessive production of NO has been found to be involved in causing
      renal injury by formatting peroxinitrite (ONOO(-)). The aim of this study was to
      investigate whether NO has a role in this damage, using aminoguanidine (AMG), a
      known iNOS inhibitor and an antioxidant, in rats undergoing MI/R. METHODS: Male
      Wistar rats were used for the experiments (n = 7 each group). In the MI/R group,
      the left coronary artery was occluded for 30 min and then reperfused for 120 min;
      the same procedure was used for the AMG group, with the additional step of AMG
      (200 mg/kg) administered 10 min prior to ischemia. A control group underwent sham
      operation. At the end of the reperfusion period, all rats were killed and their
      kidneys removed for biochemical determination and histopathological analysis.
      RESULTS: Myocardial ischemia/reperfusion in the rat kidney was accompanied by a
      significant increase in malondialdehyde and NO production, and a decrease in
      glutathione content. Administration of AMG reduced malondialdehyde and NO
      production and prevented depletion of glutathione content. These beneficial
      changes in the biochemical parameters were also associated with parallel changes
      in histopathological appearance. CONCLUSION: These findings suggest that MI/R
      plays a causal role in kidney injury and AMG exerts renal-protective effects,
      probably by inhibiting NO production and antioxidant activities.

PMID- 17010014
TI  - Evaluation of the duration of ureteral stenting following endopyelotomy: Animal
      study.
AB  - BACKGROUND: The purpose of the present paper was to evaluate whether it is
      possible to reduce the duration of ureteral stenting following endopyelotomy, and
      thus reduce side-effects. METHODS: Seventeen pigs were used. They were
      distributed at random into three groups. The study was divided as follows: phase
      I included baseline study of the urinary system and the creation of a
      ureteropelvic junction obstruction (UPJO) model. Phase II, 1 month later,
      consisted of diagnosing UPJO, Acucise endopyelotomy of the same, and the
      placement of a ureteral stent. Ureteral stents were left in situ for 1 week in
      group I, for 3 weeks in group II and 6 weeks in group III. Phase III, 3 months
      after treatment, consisted of follow up and post-mortem studies of the animals.
      The following procedures were carried out during each phase: ureteropelvic
      junction (UPJ) diameter measurement, ultrasound percutaneous and endoluminal
      studies, urine culture and determination of blood urea and creatinine levels.
      RESULTS: On removal of the stent, the presence of urinoma was observed in two
      animals in group I. There were statistically significant differences between
      group I and III with regard to evolution of the internal diameter of the UPJ.
      However, the least severe histological lesion at the UPJ level was found in group
      II. CONCLUSIONS: Ureteral stent placement for 1 week is insufficient in order to
      assure correct healing and evolution of the UPJ following endopyelotomy. Stenting
      for 3 weeks is effective, and it is not necessary to extend stenting time to 6
      weeks. Endoluminal ultrasound is of great use in determining the effects of
      endourological techniques in the ureter and the retroperitoneal space. It is also
      useful for deciding which therapeutic technique to use, and for inserting the
      Acucise in order to prevent iatrogenic problems.

PMID- 17010015
TI  - Up-regulation of interleukin-6 gene expression in cyclophosphamide-induced
      cystitis in mice: An in situ hybridization histochemical study.
AB  - AIM: To determine the time course and the cellular sources of interleukin (IL)-6
      in the bladder during experimental cystitis, the expression of the IL-6 gene and
      IL-6 protein was examined in the bladder during cyclophosphamide (CP)-induced
      cystitis. METHODS: Mice were killed at 0, 1, 2, 6, 12 and 48 h after the
      intraperitoneal administration of 0.9% saline containing either CP (200 mg/kg) or
      saline. The expression of IL-6 gene and IL-6 protein were detected using in situ
      hybridization histochemistry and immunocytochemistry, respectively. RESULTS: In
      situ hybridization histochemistry showed that IL-6 gene expression was
      significantly up-regulated in the bladder at 1 h in comparison to that at 0 h
      after CP administration. The levels of IL-6 gene expression peaked at 6 h after
      CP administration and then declined thereafter. In contrast, only a few IL-6
      transcripts were expressed in the bladder but they remained unchanged following
      the administration of saline at all time points examined. The IL-6 transcripts
      were predominantly distributed in the perivascular area of the submucosal layers
      during CP-induced cystitis. Immunocytochemistry demonstrated IL-6
      immunoreactivity in the spindle-shaped cells located in the vicinity of the
      dilated vessels of the submucosal layers during CP-induced cystitis. CONCLUSION:
      IL-6 gene expression was up-regulated in the submucosal layer of the bladder and
      peaked at 6 h after CP administration, suggesting that the primary source of IL-6
      may be fibroblasts in the bladder during CP-induced cystitis.

PMID- 17010016
TI  - EDTA-induced urothelial cell shedding for the treatment of superficial bladder
      cancer in the mouse.
AB  - AIM: The aim of this study was to determine the effect of intravesical EDTA
      instillation on the development of intravesically implanted tumor cells in normal
      mice. METHODS: The mouse bladder tumor (MBT-2) model was used in female C3H/eb
      mice to evaluate the amount of normal urothelial cell shedding, and the degree of
      tumor growth inhibition following intravesical EDTA instillation in comparison
      with phosphate-buffered saline (PBS) instillation. RESULTS: At 1 h after
      instillation, the number of urothelial cells aspirated was 500-1000 per PBS
      treated mouse and 10,000-20,000 per EDTA-treated mouse (P < 0.00001). The bladder
      weight, which reflected the effect of the agent on the tumor, was similar in the
      untreated and PBS-treated mice (105.46 +/- 46 mg and 106.2 +/- 50 mg,
      respectively). It was significantly lower in the EDTA-treated mice (80.4 +/- 42
      mg) (P = 0.0045). CONCLUSIONS: Intravesical administration of EDTA results in
      significant normal and neoplastic urothelial cell shedding. Intravesical
      irrigation with EDTA may prevent adherence of the malignant cells to the bladder
      wall following tumor resection.

PMID- 17010017
TI  - Analysis of a 1-year-old cystinuric patient with recurrent renal stones.
AB  - Cystinuria is a hereditary disorder of cystine and dibasic amino acids (lysine,
      arginine, ornithine) transport across the luminal membrane of renal tubules and
      intestine, resulting in recurrent nephrolithiasis. Cystine stones frequently
      occur in the second or third decade of life with an occasional occurrence in
      infancy and in old age. Herein is presented the case of a 1-year-old girl with
      cystinuria and recurrent urolithiasis; the genetic basis of the disease was
      investigated by mutational analysis of the SLC3A1 gene. The data show that the
      present patient has an increased cystine (923.08 microg/mL) level and was
      heterozygote for M467T mutation.

PMID- 17010018
TI  - Hydronephrosis caused by intra-abdominal abscess from cecal perforation by an
      ingested fish bone.
AB  - A patient was treated for hydronephrosis caused by an intra-abdominal abscess
      arising from cecal perforation by an ingested fish bone. To the authors'
      knowledge there is no previous report of such ureteral obstruction. Ureteral
      stenting, drainage of the abscess, and ileocecal resection were performed. Six
      months of stenting were required to attain ongoing ureteral patency following
      removal.

PMID- 17010019
TI  - Adenocarcinomas arising from primary retroperitoneal teratoma in an adult female
      patient.
AB  - Presented herein is a case of primary retroperitoneal teratoma with
      adenocarcinomatous transformation predominantly composed of signet ring cell
      carcinoma and intestinal-type adenocarcinoma in a 36-year-old woman.
      Retroperitoneum is an infrequent location for teratoma in adults and malignant
      transformation is exceptionally rare. Clinical manifestations, radiological
      studies, laboratory investigation, and pathological findings of this case are
      described. To the best of the authors' knowledge, 16 adult cases of primary
      retroperitoneal teratoma with malignant change have been reported in the
      literature. Herein is reported the first case of malignant teratoma with
      prominent component of signet ring cell carcinoma.

PMID- 17010020
TI  - Alveolar soft-part sarcoma of the retroperitoneum.
AB  - A 33-year-old woman was referred to Iida Municipal Hospital because of left back
      pain. Computed tomography showed a tumor (17 x 11 x 10 cm) in the left
      retroperitoneal space. T1- and T2-weighted magnetic resonance imaging showed an
      inhomogeneous mass with marginal blood vessels. The tumor was resected via lumbar
      oblique incision with the thoraco-abdominal approach. The tumor weighed 1800 g
      and consisted of nests of 5-100 large, loosely arranged, polygonal cells,
      surrounded by capillaries, resembling alveoli. The tumor cells were rich in
      cytoplasm, containing periodic acid-Schiff- and diastase-positive granules and
      typical crystals. The pathological diagnosis was alveolar soft-part sarcoma
      (ASPS). Alveolar soft-part sarcoma is a rare soft-tissue tumor that accounts for
      approximately 0.5-1% of soft-tissue sarcomas. Such tumors originating in the
      retroperitoneal space are extremely rare. Herein is reported a case of ASPS of
      the retroperitoneum with radiological and pathological findings.

PMID- 17010021
TI  - Genital self-mutilation.
AB  - A 53-year-old man was brought to the emergency department having removed both
      testicles and amputated his penis using a bread knife. Examination of the
      amputated penis showed it to be unsuitable for an attempted replant procedure.
      The patient was taken to theatre where the perineal wound was debrided and the
      remaining urethra brought down as a perineal urethrostomy, with a local cutaneous
      flap rotated to provide coverage for the urethra. Discussed herein are the
      incidence, predisposing factors, management and complications of genital self
      mutilation in the adult male, and the existing literature is reviewed on the
      subject.

PMID- 17010022
TI  - Granulomatous balanoposthitis after intravesical Bacillus-Calmette-Guerin
      instillation therapy.
AB  - We report a rare case of granulomatous balanoposthitis after intravesical
      Bacillus-Calmette-Guerin (BCG) instillation therapy in a 58-year-old man, which
      followed transurethral resection (TUR) for recurrent bladder cancer, when his
      anterior urethra was slightly narrow and his foreskin was with phimosis.
      Intravesical BCG instillation therapy was started for prophylaxis of recurrent
      bladder cancer after TUR. Multiple painless firm papules on glans penis, edema in
      the foreskin and low-grade fever appeared after the seventh instillation, for
      which the single antituberculous agent isoniazid (300 mg/day) was administered.
      Biopsy of the papules on glans penis and foreskin revealed granulomatous
      balanoposthitis. Low-grade fever normalized and the papules disappeared within 1
      week. The patient continued chemotherapy with isoniazid for the next 12 months.
      There was no recurrence of bladder cancer or balanoposthitis for 15 months and to
      date.

PMID- 17010023
TI  - Trends in prostate cancer incidence and survival in various socioeconomic
      classes: a population-based study.

PMID- 17010024
TI  - National Health Service Corps staffing and the growth of the local rural non-NHSC
      primary care physician workforce.
AB  - CONTEXT: Beyond providing temporary staffing, National Health Service Corps
      (NHSC) clinicians are believed by some observers to contribute to the long-term
      growth of the non-NHSC physician workforce of the communities where they serve;
      others worry that NHSC clinicians compete with and impede the supply of other
      local physicians. PURPOSE: To assess long-term changes in the non-NHSC primary
      care physician workforce of rural underserved counties that have received NHSC
      staffing support relative to workforce changes in underserved counties without
      NHSC support. METHODS: Using data from the American Medical Association and NHSC,
      we compared changes from 1981 to 2001 in non-NHSC primary care physician to
      population ratios in 2 subsets of rural whole-county health professional shortage
      areas: (1) 141 counties staffed by NHSC physicians, nurse practitioners, and/or
      physician assistants during the early 1980s and for many of the years since and
      (2) all 142 rural health professional shortage area counties that had no NHSC
      clinicians from 1979 through 2001. FINDINGS: From 1981 to 2001, counties staffed
      by NHSC clinicians experienced a mean increase of 1.4 non-NHSC primary care
      physicians per 10,000 population, compared to a smaller, 0.57 mean increase in
      counties without NHSC clinicians. The finding of greater non-NHSC primary care
      physician to population mean ratio increase in NHSC-supported counties remained
      significant after adjusting for baseline county demographics and health care
      resources (P < .001). The estimated number of "extra" non-NHSC physicians in NHSC
      supported counties in 2001 attributable to the NHSC was 294 additional physicians
      for the 141 supported counties, or 2 extra physicians, on average, for each NHSC
      supported county. Over the 20 years, more NHSC-supported counties saw their non
      NHSC primary care workforces grow to more than 1 physician per 3,500 persons, but
      no more NHSC-supported than nonsupported counties lost their health professional
      shortage area designations. CONCLUSIONS: These data suggest that the NHSC
      contributed positively to the non-NHSC primary care physician workforce in the
      rural underserved counties where its clinicians worked during the 1980s and
      1990s.

PMID- 17010025
TI  - The visiting specialist model of rural health care delivery: a survey in
      Massachusetts.
AB  - CONTEXT: Hospitals in rural communities may seek to increase specialty care
      access by establishing clinics staffed by visiting specialists. PURPOSE: To
      examine the visiting specialist care delivery model in Massachusetts, including
      reasons specialists develop secondary rural practices and distances they travel,
      as well as their degree of satisfaction and intention to continue the visiting
      arrangement. METHODS: Visiting specialists at 11 rural hospitals were asked to
      complete a mailed survey. FINDINGS: Visiting specialists were almost evenly split
      between the medical (54%) and surgical (46%) specialties, with ophthalmology,
      nephrology, and obstetrics/gynecology the most common specialties reported. A
      higher proportion of visiting specialists than specialists statewide were male (P
      = .001). Supplementing their patient base and income were the most important
      reasons visiting specialists reported for having initiated an ancillary clinic.
      There was a significant negative correlation between a hospital's number of
      staffed beds and the total number of visiting specialists it hosted (r =-0.573, P
      = .032); study hospitals ranged in bed size from 15 to 129. CONCLUSIONS: The goal
      of matching supply of health care services with demand has been elusive. Visiting
      specialist clinics may represent an element of a market structure that expands
      access to needed services in rural areas. They should be included in any
      enumeration of physician availability.

PMID- 17010026
TI  - Graduated drivers license programs and rural teenage motor vehicle fatalities.
AB  - CONTEXT: Graduated drivers license (GDL) programs have been shown to reduce motor
      vehicle fatalities among 15- to 17-year-olds. However, the 20 most rural states
      have been the least likely to enact more stringent GDL policies. PURPOSE:
      Estimate the relationship of GDL programs and the number of traffic fatalities
      among 15- to 17-year-olds on rural interstate and noninterstate roadways.
      METHODS: Analysis of 1992-2002 Fatality Analysis Reporting System data and a
      compendium of state laws using a conditional negative binominal regression model
      with full fixed effects to control for unobservable differences across states and
      years. FINDINGS: Overall, GDL programs were associated with a 7.8% reduction in
      rural traffic fatalities among 15- to 17-year-olds. Virtually all of this
      reduction took place on noninterstate roadways. The most stringent GDL programs
      were associated with a nearly 22% reduction in this age group and were the only
      programs associated with reductions in fatalities among 15- to 17-year-old
      drivers. CONCLUSIONS: Rural states should consider enacting stringent GDL
      programs. Had the 19 of the 20 most rural states without such programs all
      adopted the most stringent GDL programs in 2002, the analysis suggests that 64
      traffic deaths among 15- to 17-years-olds could have been prevented.

PMID- 17010027
TI  - Nonfatal all-terrain vehicle-related injuries to youths living on farms in the
      United States, 2001.
AB  - CONTEXT: Use of all-terrain vehicles (ATVs) in agriculture appears to be growing.
      PURPOSE: To provide estimates of ATV ownership and exposure on US farms and an
      overview of injuries to youths as a result of ATV use on the farm in 2001.
      METHODS: Analysis of the National Institute for Occupational Safety and Health
      and US Department of Agriculture 2001 Childhood Agricultural Injury Survey. These
      data, collected via telephone surveys, provide information on nonfatal injuries
      that occurred to youths younger than 20 years living on US farms during 2001. The
      injuries included both occupational and nonoccupational incidents. FINDINGS: Of
      an estimated 1.1 million youths living on farms, 36% had operated an ATV in 2001.
      Youths younger than 16 years were more likely to have operated an ATV than a
      tractor on these farms. An estimated 2,246 nonfatal ATV-related injuries occurred
      to youths younger than 20 years on US farms during 2001. The majority of these
      ATV injuries (1,668, 74%) occurred to youths identified as members of the
      household. Males accounted for 1,145 (69%) of the ATV injuries to household
      youths. The majority of the injuries were to youths aged 10-15 years (1,170,
      70%). Most ATV injuries were the result of recreational activities (970, 58%). In
      addition, many of these injury events involved youths riding without helmets and
      using ATVs that were larger than the recommended size for their age.

PMID- 17010028
TI  - Personal protective equipment use and safety behaviors among farm adolescents:
      gender differences and predictors of work practices.
AB  - CONTEXT: Children on farms perform work that places them at risk for acute and
      chronic negative health outcomes. Despite strategies for preventing and reducing
      the risk of disease and injury, children's use of personal protective equipment
      and safely equipped farm machinery has generally remained unreported. PURPOSE:
      This paper reports the use of personal protective equipment, self-protective work
      behaviors, and selected risk exposures of children aged 14-19, who perform farm
      work. METHODS: Survey results of adolescent high school students (n = 593)
      enrolled in agriculture class in Kentucky, Iowa, and Mississippi. Students were
      part of the sample that participated in the Agricultural Disability Awareness and
      Risk Education Project. FINDINGS: Boys were at a significantly higher risk of
      exposure compared to girls, and boys engaged more frequently in risky behavior.
      Hearing and respiratory protection was used minimally and sporadically. Physical
      symptoms influenced use of hearing and respirator use, as did physician
      recommendation to use such protection. Of students who operated farm tractors,
      only half most frequently operated tractors with safety bars and seat belts.
      Sixty percent of the students reported using equipment with damaged or missing
      safety shields. CONCLUSIONS: In addition to the usual risks of farm work,
      adolescents may be at even greater risk by not using personal protective
      equipment or not having access to machinery that is properly equipped for maximum
      protection. Health care providers should incorporate advice to adolescents and
      their parents on risk reduction, particularly on the use of personal protective
      equipment.

PMID- 17010029
TI  - Pharmacist staffing, technology use, and implementation of medication safety
      practices in rural hospitals.
AB  - CONTEXT: Medication safety is clearly an important quality issue for rural
      hospitals. However, rural hospitals face special challenges implementing
      medication safety practices in terms of their staffing and financial and
      technical resources. PURPOSE: This study assessed the capacity of small rural
      hospitals to implement medication safety practices, with particular focus on
      pharmacist staffing and the availability of technology. METHODS: A telephone
      survey of a national random sample of small rural hospitals was conducted from
      March to May 2005 (N = 387 hospitals, 94.6% response rate). Survey respondents
      included pharmacists (89%) and directors of nursing (11%). Multivariate analyses
      examined the relationships between hospital organizational and financial
      variables and (1) the amount of pharmacist staffing; (2) use of pharmacy
      computers for medication safety activities; and (3) implementation of medication
      safety practices. FINDINGS: Many small rural hospitals have limited hours of on
      site pharmacist coverage. Almost one quarter of hospitals either do not have a
      pharmacy computer or are not using it for clinical purposes. Half of the
      hospitals have implemented 4 key medication safety practices. Level of pharmacist
      staffing, use of technology, and implementation of medication safety practices
      are significantly related to hospital financial status and accreditation.
      CONCLUSIONS: Implementation of protocols related to medication use and key
      medication safety practices are areas where small rural hospitals could improve.
      The study results support a continuation of Medicare cost-based reimbursement
      policies to help ensure financial stability and support quality and patient
      safety activities in small rural hospitals.

PMID- 17010030
TI  - Inpatient care in rural hospitals at the beginning of the 21st century.
AB  - CONTEXT: National data documenting the role that rural hospitals play in
      providing inpatient care to patients both younger than 65 and 65 years and older
      has previously been unavailable. PURPOSE: To present descriptive nationally
      representative data on the numbers and types of inpatients, and the care they
      received, in rural hospitals. METHODS: This study includes inpatient data from
      the 2001 National Hospital Discharge Survey, a nationally representative survey
      of short-stay, nonfederal hospitals in the United States. Inpatients in rural
      hospitals were compared to those in urban hospitals in terms of demographic and
      clinical characteristics and patterns of utilization. Among the variables
      examined were age, number and type of diagnoses, avoidable hospitalizations,
      comorbidity, procedures received, source of payment, average length of stay, and
      discharge disposition. FINDINGS: Seventeen percent (5.7 million) of
      hospitalizations were in rural hospitals in 2001 and a similar percent of the US
      population lived in rural areas. Rural hospitals provided 23 million days of
      inpatient care and 4.7 million inpatient procedures. Despite the emphasis placed
      on Medicare's role in supporting rural hospitals, half of rural hospital
      inpatients were younger than 65 years. Rural hospital inpatients had shorter
      average stays and received fewer procedures on average. Seven percent of rural
      hospital inpatients were transferred to other short-stay hospitals. CONCLUSIONS:
      National data on the broad scope of patients served and inpatient services
      provided by rural hospitals illustrate one important role these hospitals play in
      serving rural communities.

PMID- 17010031
TI  - General surgery programs in small rural New York State hospitals: a pilot survey
      of hospital administrators.
AB  - CONTEXT: Hospitals play a central role in small rural communities and are
      frequently one of the major contributors to the local economy. Surgical services
      often account for a substantial proportion of hospital revenues. The current
      shortage of general surgeons practicing in rural communities may further threaten
      the financial viability of rural hospitals and communities. PURPOSE: To describe
      hospital administrators' perceptions regarding the current state of general
      surgery programs at small rural hospitals in New York State, including the impact
      that surgical services have on hospital financial viability. METHODS: A list of
      hospitals belonging to the rural hospitals group of the Healthcare Association of
      New York State was obtained to determine prospective survey recipients. Sixty
      eight administrators at each of the identified hospitals were subsequently
      surveyed and 38 respondents met all inclusion criteria. FINDINGS: Approximately
      87% of hospital administrators perceive that the general surgery program is
      critical to the hospital's financial viability. Forty percent of respondents
      report that they would be forced to close the hospital if the surgical program
      was lost. Among the 42% of administrators trying to recruit a general surgeon,
      almost two thirds have been searching for more than 1 year. CONCLUSIONS:
      According to the perceptions of hospital administrators, the financial viability
      of rural hospitals in New York State depends in large part on their ability to
      provide surgical services. Additionally, general surgeons appear to be in high
      demand at a significant number of the surveyed institutions.

PMID- 17010032
TI  - Differential effectiveness of depression disease management for rural and urban
      primary care patients.
AB  - CONTEXT: Federally qualified health centers across the country are adopting
      depression disease management programs following federally mandated training;
      however, little is known about the relative effectiveness of depression disease
      management in rural versus urban patient populations. PURPOSE: To explore whether
      a depression disease management program has a comparable impact on clinical
      outcomes over 2 years in patients treated in rural and urban primary care
      practices and whether the impact is mediated by receiving evidence-based care
      (antidepressant medication and specialty care counseling). METHODS: A preplanned
      secondary analysis was conducted in a consecutively sampled cohort of 479
      depressed primary care patients recruited from 12 practices in 10 states across
      the country participating in the Quality Enhancement for Strategic Teaming study.
      FINDINGS: Depression disease management improved the mental health status of
      urban patients over 18 months but not rural patients. Effects were not mediated
      by antidepressant medication or specialty care counseling in urban or rural
      patients. CONCLUSIONS: Depression disease management appears to improve clinical
      outcomes in urban but not rural patients. Because these programs compete for
      scarce resources, health care organizations interested in delivering depression
      disease management to rural populations need to advocate for programs whose
      clinical effectiveness has been demonstrated for rural residents.

PMID- 17010033
TI  - The state of diabetes care provided to Medicare beneficiaries living in rural
      America.
AB  - CONTEXT: Diabetes poses a growing health burden in the United States, but much of
      the research to date has been at the state and local level. PURPOSE: To present a
      national profile of diabetes care provided to Medicare beneficiaries living in
      urban, semirural, and rural communities. METHODS: Medicare beneficiaries with
      diabetes aged 18-75 were identified from Part A and Part B claims data from 1999
      to 2001. A composite of 3 diabetes care indicators was assessed (annual
      hemoglobin A1c test, biennial lipid profile, and biennial eye examination).
      FINDINGS: Over 77% had a hemoglobin A1c test, 74% a lipid profile, and 69% an eye
      examination. Patterns of care were considerably different across the urban-rural
      continuum at the state, Census division, and regional levels. States in the
      northern and eastern portions of the country had higher indicator rates for rural
      than for urban residents. States in the South had much lower rates for rural
      residents than their urban counterparts. Despite these within-state differences,
      across-state comparisons found that several states tended to have low indicator
      rates in every level of the urban-rural continuum. A common feature of these
      states was the relatively high concentration of nonwhite beneficiaries. For
      example, southern states had much higher concentrations of nonwhite beneficiaries
      relative to other areas in the country and demonstrated low rates in every level
      of the urban-rural continuum. CONCLUSIONS: Urban-rural quality of care
      differences may be a function not just of geography but also of the presence of a
      large nonwhite population.

PMID- 17010034
TI  - Comparison of rural and urban residents' implicit and explicit attitudes related
      to seeking medical care.
AB  - CONTEXT: The decision whether or not to consult a physician draws from a variety
      of attitudes within an individual's health schema. While rural Americans are in
      greater need of health care, many of them have fewer external resources than
      urbanites available to them. PURPOSE: The objective of this study was to elicit
      implicit and explicit attitudes related to seeking medical treatment for a
      condition described as fairly serious. Participants were asked to rate how often
      they comply with treatment regimens and practice good health habits. METHODS: The
      sample of rural (N = 586) and urban (N = 433) North Carolina residents was
      derived based on random-digit dialing. Multiple regression analyses were
      performed to investigate how attitudes associated with perceived compliance and
      health behaviors. FINDINGS: While rural and urban residents offered very similar
      responses, the associations between attitudes and behaviors were different. One
      healthy and 2 unhealthy schema patterns emerged. First, fear of hospitals was
      associated with effective compliance for rural residents and good health habits
      for urbanites. Second, affordability concerns were ascribed to rural community
      residents but seemed to reflect personally relevant implicit attitudes since they
      were associated with poor health adherence and habits for rural residents. Third,
      mistrust of doctors predicted low adherence for both groups and was also
      associated with poorer health habits for urbanites. With inconsistencies among
      implicit and explicit attitudes and behaviors, some residents seemed to be
      ambivalent about seeking health care.

PMID- 17010035
TI  - Concordance of patient-physician obesity diagnosis and treatment beliefs in rural
      practice settings.
AB  - CONTEXT: Although clinical guidelines recommend routine screening and treatment
      for obesity in primary care, lack of agreement between physicians and patients
      about the need for obesity treatment in the primary care setting may be an
      unexplored factor contributing to the obesity epidemic. PURPOSE AND METHODS: To
      better understand this dynamic, we surveyed 439 obese patients (body mass index
      >or=30) at the time of clinic visits in 2003 at diverse primary care settings in
      rural Kansas and conducted same-day interviews with their physicians (N = 28). We
      used Spearman's correlation to describe and compare patient and physician
      responses. FINDINGS: Most patients were women (66%). Their mean age was 55.8
      years, and mean body mass index was 37.7. Half (51%) reported discussing their
      weight on that visit date. Overall, 51% of patients wanted to discuss weight more
      often with their physician and 54% wanted to discuss weight sooner. Patients and
      physicians gave similar assessments of the patient's preference for discussing
      weight loss, how often weight was discussed at visits, and the patient's
      motivation for weight loss. Spearman's correlations on these variables were .33,
      .54, and .25, respectively (all P < .001). CONCLUSIONS: These patients and their
      physicians demonstrated a weak to moderate agreement on several variables crucial
      to initiating and continuing obesity care. Understanding patient and provider
      beliefs and preferences regarding obesity diagnosis and treatment is essential in
      designing obesity interventions for primary care.

PMID- 17010036
TI  - Preventive care in Appalachia: use of the theory of planned behavior to identify
      barriers to participation in cholesterol screenings among West Virginians.
AB  - CONTEXT: West Virginians are at increased risk for heart disease. Given that the
      process of atherosclerosis begins in childhood, the Coronary Artery Risk
      Detection in Appalachian Communities Project was developed to reduce this risk by
      implementing a cholesterol screening program in the schools. However,
      participation rates have been less than desired. PURPOSE: This study examined the
      barriers to participation in preventive health screenings, specifically
      cholesterol screenings, in adults and children of West Virginia using the theory
      of planned behavior to guide conceptualization. METHODS: A total of 14 community
      leaders, 36 parents, and 92 fifth-grade children from 6 West Virginia counties
      with predominately rural populations participated in individual and focus group
      interviews. Qualitative analysis was used to examine interview transcripts.
      FINDINGS: Adult and child attitudes about preventive care were the largest
      barrier to cholesterol screenings. Adult attitudinal barriers included concerns
      with outcomes of testing, lack of knowledge about cholesterol and heart disease,
      concerns about needles, and traditional Appalachian cultural beliefs (resistance
      to change, denial, and fatalism). Children cited concerns about needles, outcomes
      of testing, privacy, and lack of concern about health and cholesterol. Adults
      also acknowledged environmental barriers to screenings. Finally, children
      reported a lack of social pressure to participate in prevention activities.
      CONCLUSIONS: Attitudinal, social normative, and environmental barriers to health
      screenings may be characteristic of impoverished rural Appalachians.
      Interventions are being designed to target these belief barriers to improve
      participation in cholesterol screenings for fifth graders.

PMID- 17010037
TI  - Stress response of Campylobacter spp. and its role in food processing.
AB  - In many temperate countries Campylobacter spp. are the most common bacterial
      causes of human infectious intestinal disease. Yet the aetiology of this
      infection has only partly been described. A majority of human campylobacteriosis
      cases are associated with food of animal origin. Despite being very sensitive to
      environmental stressors Campylobacter spp. are able to persist in the food chain
      and can pose a threat to the consumer. In this review, the survival potential and
      stress response of Campylobacter spp. in food will be summarized and the
      importance of food preservation technologies will be discussed.

PMID- 17010038
TI  - Persistence of rabbit haemorrhagic disease virus genome in vaccinated rabbits
      after experimental infection.
AB  - Rabbit haemorrhagic disease (RHD) is usually a fatal disease in rabbits which has
      spread rapidly across the continents. While previous studies suggested
      persistence in rabbits to be an important factor in the epidemiology, the
      relevance of field virus infection of immune rabbits has not been investigated in
      experimentally infected animals before. This report describes for the first time
      the persistence of rabbit haemorrhagic disease virus (RHDV) genome for at least
      15 weeks in rabbits immunized with an inactivated vaccine as well as a subunit
      vaccine and subsequently challenged with virulent RHDV. The viral RNA loads were
      determined by real-time reverse transcription-polymerase chain reaction. No
      conspicuous association of the detectable amount of RHDV RNA with the type of
      vaccine, the time after infection and--with one exception--the level of RHDV
      specific antibodies in the immunized animals was observed. The results presented
      in this study are an urgent evidence for the existence of carrier animals as an
      important factor in the epidemiology of RHD.

PMID- 17010039
TI  - Incidence of BVDV1 and BVDV2 infections in cattle submitted for necropsy in
      Northern Germany.
AB  - The incidence of bovine viral diarrhoea virus (BVDV) 1 and 2 infections was
      determined in calves, young cattle and older cattle with signs of mucosal disease
      (MD) submitted for necropsy to three laboratories in Northern Germany between
      June 2000 and May 2001. At necropsy, tonsils, retropharyngeal lymph nodes,
      mesenteric lymph nodes, ileal Peyer's patch and spleen were collected and
      examined by immunohistochemistry and virus isolation. From 311 animals examined,
      30 (9.6%) were positive for BVDV. All viral isolates were typed by polymerase
      chain reaction after reverse transcription using species-specific primers and
      determined to be BVDV1. Based on the distribution of lesions and viral antigen,
      animals with MD, persistent infection (PI) and acute, transient infection could
      be distinguished. Twelve of the positive animals had characteristic signs of MD:
      severe diarrhoea, erosive to ulcerative lesions throughout the digestive tract
      and severe depletion of all lymphoid tissues. Viral antigen was present in all
      tissues and cell types, but particularly in depleted lymphoid follicles and
      altered epithelium. In seven calves, viral antigen was detectable in all tissues
      and cell types, but lesions were mild or missing. This is typical for PI. The
      remaining 11 calves most likely represent animals with acute, transient
      infection. Distribution of antigen was more variable, predominantly restricted to
      lymphoid follicles and often not seen in all tissues examined. Clinical findings
      were combined bronchopneumonia and enteritis. The detection of BVDV1 in young
      calves with pneumonia and enteritis emphasizes the importance of BVDV1 and not
      only BVDV2 for severe respiratory and enteric diseases of calves.

PMID- 17010040
TI  - Establishment of a competitive ELISA (cELISA) system for the detection of
      influenza A virus nucleoprotein antibodies and its application to field sera from
      different species.
AB  - A recombinant baculovirus (RBV) encoding the nucleoprotein (NP) of avian
      influenza virus (AIV) was generated and the appropriate protein was expressed in
      Sf9 cells. Purified recombinant NP and the NP-specific monoclonal antibody HB65
      were used to establish a competitive ELISA (cELISA) system for the detection of
      NP-specific antibodies in sera of ducks, geese and wild birds. Tests to evaluate
      this method were carried out using sera of ducks experimentally infected with
      AIV, pre-immune duck and chicken sera, and poultry field sera, which tested
      negative in the haemagglutination inhibition (HI) assay, and field sera of
      several poultry species experimentally infected with other viruses. The
      evaluation of the test demonstrated a high sensitivity and specificity of this
      method. Tests carried out using field sera of duck and goose flocks revealed
      widely corresponding results obtained by HI assay and cELISA indicating that this
      test is applicable for flock diagnosis. Differing results were obtained for
      individual samples. It can be assumed that for the most part this was because of
      a better recognition of the conserved NP antigen by serum antibodies, although
      some results remained unclear.

PMID- 17010041
TI  - Detection and identification of food-borne pathogens of the genera Campylobacter,
      Arcobacter and Helicobacter by multiplex PCR in poultry and poultry products.
AB  - The objective of this study was to develop a multiplex polymerase chain reaction
      (PCR) to detect and differentiate food-borne pathogens of the three genera
      Campylobacter, Arcobacter and Helicobacter in a single step procedure. One common
      reverse primer and three genus-specific forward primers were designed by
      hybridizing to the 16S rRNA of selected reference strains. Besides the species
      with significance as food-borne pathogens isolated from poultry meat-
      Campylobacter jejuni, Campylobacter coli, Arcobacter butzleri and Helicobacter
      pullorum--several other members of these genera were tested to determine the
      specificity of the designed multiplex PCR. In total, 20 ATCC and NCTC reference
      strains of Campyobacter, Arcobacter and Helicobacter were used to evaluate the
      PCR. Specific amplificates were obtained from all thermophilic species of
      Campylobacter as well as from species of Arcobacter and Helicobacter. No
      amplification product was obtained from the non-thermophilic Campylobacter, C.
      hyointestinalis and C. fetus. Furthermore, a total of 43 field strains of the
      three genera isolated from poultry, pigs, cattle and humans were investigated
      using this PCR. To confirm the classification of 10 H. pullorum strains the 16S
      rRNAs were sequenced. The developed PCR is a helpful diagnostic tool to detect
      and differentiate Campylobacter, Arcobacter and Helicobacter isolated from
      poultry and poultry products.

PMID- 17010042
TI  - Prevalence of Yersinia enterocolitica in goat herds from Northern Germany.
AB  - The prevalence of human pathogenic Yersinia enterocolitica isolates in livestock
      farming is of paramount interest. Raw goat milk has been proposed as a source of
      human yersiniosis; however, no data on the prevalence of human strains of Y.
      enterocolitica in goat herds are available. Therefore, fecal samples (n = 575)
      were collected from 24 goat herds from Lower Saxony, northern Germany. Pre
      enrichment in peptone, sorbitol and bile salts broth was followed by plating on
      cefsuloidin irgasan novobiocin agar. Yersinia enterocolitica was isolated from 17
      (3%) samples of five (21%) goat herds. All isolates were biovar 1A, but
      represented various serovars. PCR assays targeting Yersinia adhesin (yad) gene
      and the yopT gene, both associated with pathogenicity, produced no amplification
      products. Therefore, the isolates can be regarded as opportunistic apathogenic
      bacteria. Consequently, milk, cheese or meat from goats should not be considered
      as an important source for human yersiniosis.

PMID- 17010043
TI  - Outbreak of tuberculosis caused by Mycobacterium caprae in a zoological garden.
AB  - In the autumn of 2004, tuberculosis caused by Mycobacterium caprae occurred in a
      zoo in Slovenia. A dromedary camel (Camelus dromedarius) was killed after a
      history of progressive emaciation. Necropsy findings indicated disseminated
      tuberculosis, which was confirmed by cultivation of M. caprae. Consequently, a
      tuberculin skin test was performed in all epidemiologically linked animals and
      another dromedary camel and six bison (Bison bison) were positive and killed.
      Mycobacterium caprae was isolated from two bison while M. scrofulaceum and
      Mycobacterium spp. were found in two other bison, respectively. The second
      dromedary camel was found to be negative for mycobacteria under both microscopic
      and culture tests. The isolates were investigated with commercial identification
      kits, IS6110 PCR, IS6110 restriction fragment length polymorphism analysis,
      spoligotyping and mycobacterial interspersed repetitive units typing. Genotyping
      results revealed that the dromedary camel and the two bison were infected by the
      same M. caprae.

PMID- 17010044
TI  - Application of paramagnetic beads for purifying Bacillus anthracis protective
      antigen.
AB  - Paramagnetic beads coated with Protein G and Tosylactivated-280 dynabeads have
      been used to purify Bacillus anthracis protective antigen from a liquid culture.
      The obtained protein was used in the enzyme-linked immunosorbent assay test to
      detect B. anthracis protective antigen antibodies in human sera collected from
      immunized individuals. The purification method using paramagnetic beads is very
      effective. It is fast, easy and may be carried out practically in any laboratory.

PMID- 17010045
TI  - Detection of Echinococcus multilocularis in foxes: evaluation of a protocol of
      the intestinal scraping technique.
AB  - The intestinal scraping technique (IST) is widely used for the detection of
      definitive hosts infected with Echinococcus multilocularis. The sensitivity of
      the method has been questioned in recent years. Several variations of the
      technique are used that may differ in their performance. We therefore estimated
      the diagnostic sensitivity and specificity of the IST protocol used in our lab by
      examining the small intestines of 210 E. multilocularis-infected foxes and 294
      foxes that had tested negative for this parasite. To this end, IST was first
      performed on 48 and 294 intestines from infected and uninfected foxes
      respectively, followed by an examination of the entire remaining mucosa of the
      small intestine to discover any infections with E. multilocularis that had not
      been detected by IST. The point estimate for diagnostic sensitivity was 100%.
      Five different classes of infection intensities were formed. The lower limits of
      the 95% confidence intervals ranged between 76.8% and 92.6% depending on the
      number of samples analysed per class. When the small intestines of another 162
      infected foxes were examined by IST and the results recorded separately for the
      anterior, middle and posterior third of the small intestine, a strong preference
      of E. multilocularis for the posterior third was observed. For epidemiological
      purposes, it may thus be possible to restrict routine investigations to the
      posterior portion of the small intestine. By contrast, a reduction of the number
      of slides examined per infected animal may lead to a considerable loss in
      sensitivity in animals with a low intensity of infection.

PMID- 17010046
TI  - Influence of climatic and management factors on Eimeria infections in goats from
      semi-arid zones.
AB  - A survey of Eimeria infections was performed in dairy goats and kids (<6 months
      old) of six farms from a dry desert area of Gran Canaria Island (Spain). The
      number of oocysts per gram of faeces (OPG) was determined by a modified McMaster
      technique over a total of 2,616 individual faecal samples taken from the rectum
      in monthly intervals. Eimeria oocysts were found in 96.1% of the samples with OPG
      ranging from 1 x 10(2) to 1.4 x 10(6). Kid goats had significantly (P < 0.001)
      higher OPG counts (46,496 +/- 5,228) than dairy females (2,225 +/- 287). Eight
      Eimeria species were identified, with Eimeria ninakohlyakimovae (30.0%), Eimeria
      arloingi (28.6%) and Eimeria alijevi (20.5%) being the most frequent species
      followed by Eimeria caprina (9.1%), Eimeria christenseni (4.5%), Eimeria
      jolchijevi (3.4%), Eimeria caprovina (3.2%) and Eimeria hirci (0.7%). Although
      significant differences were observed among goat groups and herds, the eight
      species were present in the six farms in both dairy goats and kids. The intensity
      of oocysts shedding was related to some factors such as the size of the herd and
      was further influenced by the prevailing climatic conditions of the area. The
      highest OPG counts were recorded during the hot season in dairy goats and close
      to weaning time in kids reared in small farms having no prophylactic treatments
      against eimeriosis.

PMID- 17010047
TI  - Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination
      therapy in patients with relapsed or refractory multiple myeloma: a prospective,
      multicentre, phase II, single-arm study.
AB  - We assessed the safety and efficacy of melphalan, arsenic trioxide (ATO) and
      ascorbic acid (AA) (MAC) combination therapy for patients with multiple myeloma
      (MM) who failed more than two different prior regimens. Patients received
      melphalan (0.1 mg/kg p.o.), ATO (0.25 mg/kg i.v.) and AA (1 g i.v) on days 1-4 of
      week 1, ATO and AA twice weekly during weeks 2-5 and no treatment during week 6
      of cycle 1; during cycles 2-6, the schedule remained the same except ATO and AA
      were given twice weekly in week 1. Objective responses occurred in 31 of 65 (48%)
      patients, including two complete, 15 partial and 14 minor responses. Median
      progression-free survival and overall survival were 7 and 19 months respectively.
      Twenty-two patients had elevated serum creatinine levels (SCr) at baseline, and
      18 of 22 (82%) showed decreased SCr levels during treatment. Specific grade 3/4
      haematological (3%) or cardiac adverse events occurred infrequently. Frequent
      grade 3/4 non-haematological adverse events included fever/chills (15%), pain
      (8%) and fatigue (6%). This steroid-free regimen was effective and well tolerated
      in this heavily pretreated group. These results indicate that the MAC regimen is
      a new therapeutic option for patients with relapsed or refractory MM.

PMID- 17010048
TI  - Global tests of haemostasis in critically ill patients with severe sepsis
      syndrome compared to controls.
AB  - Haemostatic changes in septic patients are complex, with both procoagulant and
      anticoagulant changes. Thirty-eight patients with severe sepsis and 32 controls
      were investigated by coagulation screens, individual factor assays, calibrated
      automated thrombography (CAT), whole blood low-dose-tissue factor activated (LD
      TFA) Rotem and LD-TFA waveform analysis. Thirty-six of 38 patients had an
      abnormal coagulation screen. The mean levels of factors II, V (P < 0.05), VII, X,
      XI and XII, antithrombin and protein C (P < 0.01) was decreased in sepsis
      compared with controls. The mean factor VIII and fibrinogen level (P < 0.001) was
      increased. CAT in platelet rich and poor plasma showed a prolonged lag time (P <
      0.02), decreased peak thrombin (P < 0.02) and delayed time to peak thrombin (P <
      0.001) in sepsis patients, however, the endogenous thrombin potential was
      equivalent in sepsis and controls. In LD-TFA Rotem, septic patients had delayed
      clot times (P = 0.04) but an increased maximum velocity of clot formation (P <
      0.01) and area under the clot elasticity curve (P < 0.01). LD-TFA waveform
      analysis showed a delayed onset time but an increased rate of clot formation (P <
      0.005). In conclusion, global tests of haemostasis suggest that in this patient
      group, activation of haemostasis is delayed but once initiated thrombin
      generation and clot formation are normal or enhanced.

PMID- 17010050
TI  - Adolescents and young adults successfully restore lymphocyte homeostasis after
      intensive T-cell depleting therapy for cancer.

PMID- 17010049
TI  - Oxidative stress and inflammation in iron-overloaded patients with beta
      thalassaemia or sickle cell disease.
AB  - Blood transfusion therapy is life-saving for patients with beta-thalassaemia and
      sickle cell disease (SCD), but often results in severe iron overload. This pilot
      study examined whether the biomarkers of tissue injury or inflammation differ in
      these two diseases. Plasma malondialdehyde (MDA) was significantly increased 1.8
      fold in thalassaemia relative to control patients. In contrast, MDA in SCD was
      not significantly different from controls. In multivariate analysis, the
      strongest predictors of elevated MDA were liver iron concentration (P < 0.001)
      and specific diagnosis (P = 0.019). A significant 2-fold elevation of non
      transferrin bound iron (NTBI) was observed in thalassaemia relative to SCD. NTBI
      was not a significant predictor of high MDA in multivariate analysis. SCD
      patients showed a significant 2.2-fold elevation of the inflammatory marker
      interleukin (IL)-6 relative to controls, and a 3.6- and 1.7-fold increase in IL-5
      and IL-10 relative to thalassaemia. Although alpha-tocopherol was significantly
      decreased by at least 32% in both thalassaemia and SCD, indicating ongoing
      oxidant stress and antioxidant consumption, gamma-tocopherol, a nitric oxide
      selective antioxidant, was increased 36% in SCD relative to thalassaemia. These
      results demonstrate that thalassaemia patients have increased MDA and circulating
      NTBI relative to SCD patients and lower levels of some cytokines and gamma
      tocopherol. This supports the hypothesis that the biology of SCD may show
      increased inflammation and increased levels of protective antioxidants compared
      with thalassaemia.

PMID- 17010051
TI  - Endocrine Treatment and Prevention of Breast and Gynecological Cancers Vth
      International Symposium of the Flemish Gynecological Oncology Group, January 26
      28, 2006.

PMID- 17010052
TI  - Anthropometry, physical activity, and endometrial cancer risk: results from the
      Netherlands cohort study.

PMID- 17010054
TI  - Exogenous steroids for menopausal symptoms and breast/endometrial cancer risk.
AB  - A literature search was performed to collect information concerning hormone
      replacement therapy (HRT) for menopausal symptoms by exogenous steroids and
      breast and endometrial cancer risk. Relevant studies in English were selected
      from Medline. HRT can alleviate vasomotor symptoms at least partially. HRT in
      women >50 years of age induces increased risk of breast and endometrial cancer.
      In women <50 years of age, HRT does not completely negate the breast cancer risk
      reduction by premature menopause. No data exist on endometrial cancer risk in
      these young women taking HRT. In conclusions, the decision to use HRT should be
      weighed against the risks and discouraged in women older than 50 years of age and
      after breast cancer. Counseling should be performed in an individual manner.

PMID- 17010053
TI  - Androgens and breast cancer.

PMID- 17010055
TI  - Insulin-like growth factor-1 genotype predicts breast volume after pregnancy and
      hormonal contraception and is associated with circulating insulin-like growth
      factor-1 levels: implications for risk of early-onset breast cancer in young
      women from hereditary breast cancer families.
AB  - BACKGROUND: BRCA1/2 mutations predispose to early-onset breast cancer, especially
      after oral contraceptive (OC) use and pregnancy. However, the majority of breast
      cancers might be due to more prevalent low penetrance genes that may also modify
      the risk in BRCA1/2 mutation carriers. The absence of the IGF1 19-CA repeat
      allele has been associated with high insulin-like growth factor-1 (IGF-1) levels
      during OC use in nulliparous women of four different ethnic groups. High IGF-1
      levels are linked to an increased risk of early-onset breast cancer and to larger
      breast volumes in the general population. It has also been hypothesized that
      women whose breast size increases while exposed to OCs may be at increased risk
      of future breast cancer. AIM: We explored the effect of the IGF1 genotype,
      specifically the absence of the common 19-CA repeat allele in the promoter region
      of the IGF1 gene, in combination with oral contraceptive (OC) use or parity on
      breast volume and IGF-1 levels. MATERIALS AND METHODS: Two hundred fifty-eight
      healthy women, </=40 years old, from hereditary breast cancer families
      participated in this prospective study. Twenty-three women were known BRCA1
      mutation carriers, 7 women were known BRCA2 mutation carriers, 54 women were
      noncarriers from BRCA1/2 families, 111 women belonged to breast cancer families
      where no BRCA1 or BRCA2 mutations were detected, and 63 women were untested from
      high-risk breast cancer families. All women completed a questionnaire including
      information on reproductive factors and OC use. We measured height, weight,
      breast volumes, and plasma IGF-1 levels once during menstrual cycle days 5-10 and
      once again during menstrual cycle days 18-23. The IGF1 genotype was successfully
      analyzed with polymerase chain reaction and fragment analyses in 254 women.
      RESULTS: Thirteen percent had no IGF1 19-CA repeat allele. The absence of the 19
      CA repeat allele was more common among women with known BRCA1 mutations compared
      to other women (26% versus 12%; P= 0.05). See updated and revised Table 1 from
      original publication. IGF-1 levels were similar among parous and nulliparous
      women not using OCs, which is in contrast to results from women in the general
      population, where parous women have lower IGF-1 levels than nulliparous women.
      Furthermore, OC use did not affect IGF-1 levels in parous women in our study.
      BRCA mutation status did not affect age-adjusted IGF-1 levels in either cycle
      phase among nonusers. Most of the nulliparous OC users had lower IGF-1 levels
      than nonusers. However, there was an interaction between IGF1 genotype and OC use
      on IGF-1 levels in nulliparous women (P= 0.026). Compared with nonusers, IGF-1
      levels were highly suppressed in OC users with a 19-CA repeat allele (P < 0.001),
      but not among women lacking the 19-CA repeat allele (P= 0.81). We also observed
      an interaction between parity and IGF1 genotype on breast volume (P= 0.01).
      Absence of the 19-CA repeat allele was associated with larger breast volumes in
      parous versus nulliparous women and OC users, while parous women and OC users
      with the 19-CA repeat allele had smaller breast volumes than nulliparous women
      and nonusers adjusted for body weight. During follow-up, six incident breast
      cancers cases occurred, four in known BRCA1 mutation carriers and two in untested
      women. Incident breast cancers were associated with absence of the 19-CA repeat
      allele (log-rank; P= 0.002). CONCLUSION: Our results suggest that absence of the
      IGF1 19-CA repeat allele modifies IGF-1 levels, breast volume, and possibly early
      onset breast cancer risk after hormone exposure in young, high-risk women. These
      results warrant confirmation in a larger prospective cohort of high-risk women.
      If confirmed, the IGF1 genotype could be incorporated as an additional marker to
      improve risk estimates for early-onset breast cancer during genetic counseling of
      women from high-risk breast cancer families.

PMID- 17010056
TI  - An update on breast cancer prevention trials.
AB  - In recent years, the question of whether breast cancer can be prevented has been
      examined in a number of large clinical trials, employing either selective
      estrogen receptor modifiers such as tamoxifen and raloxifene or aromatase
      inhibitors. In this paper, we review the most prominent studies, all of which are
      either under way or in follow-up.

PMID- 17010057
TI  - An update on raloxifene.

PMID- 17010058
TI  - Not all selective estrogen response modulators are created equal: update on
      lasofoxifene.

PMID- 17010059
TI  - Adjuvant therapy for postmenopausal ER-positive breast cancer. Why tamoxifen
      still has a future? The Leuven point of view.

PMID- 17010060
TI  - An update on ovarian suppression/ablation.
AB  - Adjuvant ovarian function suppression is acknowledged today as effective therapy
      for premenopausal patients with early breast cancer. Various modalities have been
      applied to achieve this treatment option: First, early investigations comparing
      ovarian ablation with chemotherapy identified similar outcomes in terms of
      patients' rates of disease-free survival (DFS). Second, prospective randomized
      trials have more recently focused on luteinizing hormone-releasing hormone
      analogues (LHRHa) that induce medical ovarian suppression and avoid the morbidity
      and irreversibility associated with surgical ovariectomy or irradiation. These
      trials analyzed the value of treatment with goserelin or other LHRHa, with or
      without tamoxifen, as against chemotherapy. Goserelin was subsequently
      established as a valid alternative, and our own results demonstrated that
      goserelin + tamoxifen is more effective and better tolerated in hormone
      responsive patients. Third, other multiple-arm studies have compared LHRHa +
      chemotherapy with chemotherapy alone. Addition of tamoxifen to goserelin +
      chemotherapy was shown to improve DFS, and significant benefits in goserelin
      treated patients were seen irrespective of use of chemotherapy or tamoxifen.
      Finally, ongoing trials are addressing the appropriate duration of LHRHa therapy
      and other unresolved issues. In summary, combined ovarian suppression with
      adjuvant goserelin and tamoxifen is considered to be at least as effective as
      chemotherapy in premenopausal breast cancer patients. Published reports have
      demonstrated that ovarian suppression is a safe means of reducing risk of
      recurrence in estrogen receptor-positive women and underlined its use as a
      competitive alternative to chemotherapy in this patient subset.

PMID- 17010061
TI  - Endometrial safety of third generation aromatase inhibitors versus tamoxifen in
      breast cancer patients.
AB  - The estrogenic activity of tamoxifen on the uterus increases the risk of
      developing benign and malignant uterine pathologies in breast cancer patients
      receiving this drug. This has led to gynecological interventions specifically in
      symptomatic women to exclude malignant disease. Given this known side effect
      associated with tamoxifen therapy, newer endocrine therapies such as the third
      generation aromatase inhibitors have been compared to tamoxifen also in terms of
      their uterine effects. To date, studies that have directly compared the uterine
      effects of tamoxifen with that of aromatase inhibitors generally show that
      aromatase inhibitors such as anastrozole, letrozole, and exemestane are
      associated with less uterine pathologies compared to tamoxifen. Furthermore,
      aromatase inhibitors may even reverse uterine abnormalities induced by tamoxifen.
      This implies that the absence of a stimulatory effect on the uterus would be one
      of the benefits gained with aromatase inhibitor therapy and may decrease or even
      obviate the need for gynecological interventions.

PMID- 17010062
TI  - Bone safety of aromatase inhibitors versus tamoxifen.
AB  - Bone loss may be a potential side effect of implementing aromatase inhibitors in
      the adjuvant setting. Current evidence suggests a minor bone loss during
      treatment with the steroidal aromatase inhibitor exemestane compared to placebo
      and a nonsignificant increase in fracture rate during treatment with exemestane
      when compared to tamoxifen. Such a difference could be due to the bone-sparing
      effects of tamoxifen. For the nonsteroidal inhibitors letrozole and anastrozole,
      the MA17 study revealed a nonsignificant increase in fracture rate for letrozole
      compared to placebo. In contrast, both anastrozole and letrozole were found to
      significantly increase fracture rate compared to tamoxifen when administered as
      monotherapy or given sequentially. While an increased fracture rate may have
      detrimental effects, evidence suggests that enhanced bone loss may be preventable
      through careful bone mineral density (BMD) assessment and treatment with
      bisphosphonates.

PMID- 17010063
TI  - Is fulvestrant ("Faslodex") just another selective estrogen receptor modulator?

PMID- 17010064
TI  - Metastatic breast cancer: sequencing hormonal therapy and positioning of
      fulvestrant.
AB  - Fulvestrant, a novel estrogen receptor (ER) antagonist with no agonist effects,
      binds, blocks, and degrades the ER, thereby downregulating cellular ER levels,
      which in turn leads to reduced expression of the progesterone receptor. Due to
      this specific working mechanism, fulvestrant is an important addition to the
      armamentarium of endocrine agents in advanced breast cancer (ABC). Fulvestrant
      has been shown to be equally effective as the third-generation aromatase
      inhibitor (AI) anastrozole in postmenopausal patients with hormone-sensitive ABC
      progressing prior to tamoxifen. In another randomized phase III trial, it was
      shown that fulvestrant had similar efficacy to tamoxifen in the first-line
      treatment of postmenopausal women with hormone receptor-positive ABC. When
      comparing the side effects of fulvestrant with tamoxifen and anastrozole, it was
      shown that fulvestrant is well tolerated compared with these agents and is
      associated with a lower incidence of joint disorders. Clinical benefit on
      fulvestrant treatment after AI therapy has been reported in a substantial number
      of patients (28-46%). On the other hand, it was also shown that sensitivity to
      further endocrine therapy is retained following progression on first-line or
      second-line fulvestrant (57% and 46% clinical benefit, respectively). In
      conclusion, fulvestrant provides us with an additional endocrine treatment option
      making it possible to prolong the time that patients with ABC can be treated with
      endocrine therapy.

PMID- 17010065
TI  - Endometrial cancer: predictors of response and preferred endocrine therapy.

PMID- 17010066
TI  - How to measure and report the estrogen (and progesterone) receptor in breast
      cancer.

PMID- 17010067
TI  - Better predictive factors in endocrine-responsive breast cancer than the estrogen
      receptor itself.

PMID- 17010068
TI  - Gene expression profiling of treatment resistance: hype or hope for therapeutic
      target identification.

PMID- 17010069
TI  - Targeting downstream effectors of epidermal growth factor receptor/HER2 in breast
      cancer with either farnesyltransferase inhibitors or mTOR antagonists.
AB  - In breast cancer, there is an increasing recognition of the pivotal role played
      by the epidermal growth factor receptor (EGFR) and HER2 together with the various
      downstream signal transduction pathways, in particular the Ras/Raf/Mek/erk1/2
      pathway that regulates cell proliferation together with the phosphatidylinositol
      3-OH kinase (PI3K)/Akt/mTOR pathway that is implicated in cell survival. While
      monoclonal antibodies and small molecule tyrosine kinase inhibitors targeted
      against EGFR/HER2 are now being used for breast cancer therapy, there is
      considerable interest in also targeting the critical downstream pathways that
      cells may remain dependent upon. Activation of these downstream pathways in
      breast cancer may be associated with resistance to either conventional endocrine
      or cytotoxic therapies or, indeed, lack of response to EGFR/HER2-targeted
      approaches. Farnesyltransferase inhibitors (FTIs) were initially developed to
      target Ras activation, although their mechanism of action may be more
      nonspecific. Trials in breast cancer have been completed with FTIs alone or in
      combination with endocrine or cytotoxic therapy. Activation of the PI3K/Akt
      pathway has also been associated with resistance to either tamoxifen or estrogen
      deprivation, and preclinical studies have shown that the mTOR antagonists can
      restore endocrine sensitivity in breast cancer cells. Randomized phase II/III
      trials of aromatase inhibitors combined with mTOR antagonists are in progress and
      have been powered to detect whether combined therapy can significantly prolong
      time to disease progression compared to endocrine therapy alone. Finally,
      preclinical experiments are now investigating whether downstream agents should be
      combined with upstream EGFR/HER2 therapies to produce maximal blockade of
      vertical signal transduction pathways. Subsequent trials will be needed to see
      whether combinations of novel STIs are well tolerated and how they may further
      enhance clinical benefit in breast cancer.

PMID- 17010070
TI  - Is cancer risk related to genes for steroid receptors and estrogen metabolism?

PMID- 17010071
TI  - Association between the CHEK2*1100delC germ line mutation and estrogen receptor
      status.
AB  - Already published data were further analyzed regarding the association between
      the CHEK2*1100delC germ line mutation and estrogen receptor (ER) status in
      patients with breast cancer. The CHEK2*1100delC mutation was more prevalent among
      the patients with a positive ER status (4.2% versus 1.0%). An ER-negative status
      was beside CHEK2*1100delC mutation and independently associated with an earlier
      of age onset of breast cancer. There was a trend that an ER-negative status,
      beside the presence of a CHEK2*1100delC mutation, was associated with a worse
      disease-free survival. There might be an association between ER status and a
      CHEK2*1100delC mutation. More studies with larger number of patients are needed
      to further investigate the relation between CHEK2*1100delC and ER status.

PMID- 17010072
TI  - Interleukin-1alpha protein secretion in breast cancer is associated with poor
      differentiation and estrogen receptor alpha negativity.
AB  - While interleukins (IL)-1alpha and beta are thought to play an important role in
      malignant disease, little is still known about their expression in breast cancer.
      We have used reverse transcription-polymerase chain reaction, enzyme-linked
      immunosorbent assay (ELISA), and immunohistochemistry (IHC) to analyze the
      expression of IL-1alpha and beta in breast cancer tissues, and compared their
      expression to estrogen receptor (ER) status and grading. In breast cancer cell
      lines, we found an inverse correlation between IL-1alpha and beta gene expression
      and differentiation, and only one highly invasive tumor cell line expressed IL
      1alpha protein, while IL-beta was not detectable. Breast cancer tissue expressed
      variable amounts of IL-1alpha and beta messenger RNA, but consistently high
      levels of IL-1 type I receptor. IL-1alpha protein was detectable in malignant
      epithelium and adjacent stroma in 88% of cases. IL-1alpha expression was
      correlated with poor differentiation (P= 0.002; r= 0.469) and decreasing ERalpha
      expression (P= 0.004; r=-0.387). Stromal IL-1alpha was confined to areas with low
      or absent ERalpha protein expression in adjacent tumor epithelium (P= 0.001; r=
      0.457). Taken together, we have demonstrated a functional IL-1 system in breast
      cancer and observed an inverse correlation between IL-1alpha and sex steroid
      receptor expression. We suggest that the expression of IL-1alpha in poorly
      differentiated, ERalpha-negative tumors contributes to their malignant phenotype.

PMID- 17010073
TI  - Effects of 17beta-estradiol, progesterone, synthetic progestins, tibolone, and
      raloxifene on vascular endothelial growth factor and Thrombospondin-1 messenger
      RNA in breast cancer cells.
AB  - To determine the effect of 17beta-estradiol, raloxifene, progesterone,
      medroxyprogesterone acetate (MPA), levonorgestrel (LNG), norethindrone (NET),
      tibolone and tibolone metabolites on vascular endothelial growth factor (VEGF)
      isoforms 121 and 165 and Thrombospondin-1 (TSp-1) messenger RNA (mRNA) in two
      breast cancer cell lines, MCF-7 and T47-D. MCF-7 and T47-D cells were cultured to
      80% confluence, in vitro. After 24 h incubation in serum-free media, 1.0, 0.1,
      and 0.01 muM of 17beta-estradiol, raloxifene, raloxifene plus ICI 182780,
      tibolone, 3alpha-hydroxytibolone, and 3beta-hydroxytibolone were added to MCF-7
      cells. Progesterone, MPA, LNG, NET, and Delta(4) tibolone at 1.0, 0.1, and 0.01
      muM were added to T47-D cells. The cells plus steroids were incubated for a
      further 24 h. Total RNA was isolated using TRIZOL and reverse transcriptase
      polymerase chain reaction was carried out using primers for VEGF, TSP-1, and
      cyclophilin, the latter as an internal control. Semiquantitative analysis was
      performed using 33P-CTP for radioactive labeling during the polymerase chain
      reaction. 17beta-estradiol, raloxifene, tibolone, 3alpha-hydroxytibolone, and
      3beta-hydroxytibolone had no effect on VEGF mRNA in MCF-7 cells. Progesterone,
      MPA, LNG, and NET increased VEGF mRNA in T47-D cells. Delta(4) tibolone also
      increased VEGF mRNA but to a lesser extent than the progestogens. Raloxifene
      increased TSP-1 mRNA, this effect was not reversed by the addition of ICI 182780
      to the media. 17beta-estradiol, raloxifene, tibolone and tibolone hydroxy
      metabolites had no effect on VEGF mRNA in MCF-7 cells. Progesterone and
      progestins increased VEGF mRNA in T47-D breast cancer cells. Delta(4) tibolone
      was less effective than progestogens on this angiogenic gene in the T47-D cells.
      Raloxifene increased TSP-1. These differential effects may be related to breast
      cancer growth.

PMID- 17010074
TI  - An estrogen receptor alpha-dependent regulation of estrogen receptor-related
      receptor alpha in the proliferation of endometrial carcinoma cells.
AB  - Estrogen receptor-related receptor alpha (ERRalpha) was reported to compete with
      estrogen receptor alpha (ERalpha) in a constitutive manner as an orphan nuclear
      closely related to (ERalpha). To discuss the role of ERRalpha in the endometrial
      carcinoma cells, this study was performed. ER-responsive endometrial carcinoma
      cells Ishikawa and ER-nonresponse HEC-1A cells were treated with different
      concentration of 17beta-E2 or E2 plus ICI 182780. Semiquantitative reverse
      transcription-polymerase chain reaction and western blot were performed to
      analysis the expression of human estrogen receptor-related receptor alpha
      (hERRalpha). Plasmid PLXSN-hERRalpha was constructed and transfected into cells.
      Selected in the medium containing high-dose G418, the Ishikawa and HEC-1A cells
      with stable overexpression of hERRalpha were constructed and renamed as
      Ishikawa/hERRalpha and HEC-1A/hERRalpha, respectively. To discuss the effect of
      overexpression of hERRalpha in the cell biological behavior (3-[4,5-dimethylth
      lazol-2yl]-2,5-diphenyltetrazolium bromid) (MTT) cell assay was performed.
      Estrogen downregulates ERRalpha expression in ER-positive Ishikawa cells, while
      upregulates the expression of ERRalpha in ER-negative HEC-1A cells. In Ishikawa
      cells, the downregulation of 17beta-E2 in ERRalpha expression cells could be
      blocked by ICI 182780. A decreasing expression of hERalpha was observed in the ER
      responsive cells with overexpression of ERRalpha (Ishikawa/hERRalpha).
      Overexpression of hERRalpha inhibits the cell proliferation in the ERalpha
      responsive Ishikawa cells and stimulated the cell proliferation in the ERalpha
      nonresponsive HEC-1A cells. Function of hERRalpha depends on the expression and
      function of hERalpha. ER-mediated signaling might be the important factor
      resulting in the hormone-dependent endometrial carcinoma, whereas ERRalpha
      mediated pathway might act as the vital role in hormone-independent endometrial
      carcinoma.

PMID- 17010075
TI  - Growth patterns and the risk of breast cancer in women.
AB  - Adult height and body mass index (BMI) influence the risk of breast cancer in
      women. Whether these associations reflect growth patterns of the fetus or growth
      during childhood and adolescence is unknown. We investigated the association
      between growth during childhood and the risk of breast cancer in a cohort of
      117,415 Danish women. Birth weight, age at menarche, and annual measurements of
      height and weight were obtained from school health records. We used the data to
      model individual growth curves. Information on vital status, age at first
      childbirth, parity, and diagnosis of breast cancer was obtained through linkages
      to national registries. During 3,333,359 person-years of follow-up, 3340 cases of
      breast cancer were diagnosed. High birth weight, high stature at 14 years of age,
      low BMI at 14 years of age, and peak growth at an early age were independent risk
      factors for breast cancer. Height at 8 years of age and the increase in height
      during puberty (8-14 years of age) were also associated with breast cancer. The
      attributable risks of birth weight, height at 14 years of age, BMI at 14 years of
      age, and age at peak growth were 7%, 15%, 15%, and 9%, respectively. No effect of
      adjusting for age at menarche, age at first childbirth, and parity was observed.
      Birth weight and growth during childhood and adolescence influence the risk of
      breast cancer.

PMID- 17010076
TI  - Cost-effectiveness of anastrozole compared to tamoxifen in hormone receptor
      positive early breast cancer. Analysis based on the ATAC trial.
AB  - The 5-year completed treatment analysis of the Anastrozole and Tamoxifen-Alone or
      in Combination (ATAC) trial showed the superiority of anastrozole over tamoxifen
      for reduction of disease progression in patients with hormone receptor-positive
      (HR+) early breast cancer (EBC). The objective was to evaluate the cost
      effectiveness of anastrozole versus tamoxifen in this setting. A health economic
      model was developed comparing the natural history of EBC patients treated with
      anastrozole or tamoxifen. The perspective of the Belgian health care system was
      taken. Disease progression from EBC was obtained from the ATAC trial and further
      progression beyond the clinical trial from published literature. Resource use
      data were obtained from the ATAC study and from published local retrospective
      data. Anastrozole was cost-effective versus tamoxifen, provided that a time
      horizon of at least 9 years is taken. This sensitivity to time horizon is
      inherently associated with the adjuvant setting due to the different evolution of
      costs and outcomes over time. Costs are incurred solely during the first 5 years,
      whereas outcomes are cumulated beyond adjuvant treatment. In conclusion, provided
      that a sufficient time horizon is taken and that long-term model predictions are
      confirmed from further follow-up from the ATAC study, anastrozole is a highly
      cost-effective adjuvant therapy compared to tamoxifen.

PMID- 17010085
TI  - Abstracts of the 29th Study Group on IgA Nephropathy. January 28, 2006. Tokyo,
      Japan.

PMID- 17010096
TI  - Dissociation of food and opiate preference by a genetic mutation in zebrafish.
AB  - Both natural rewards and addictive substances have the ability to reinforce
      behaviors. It has been unclear whether identical neural pathways mediate the
      actions of both. In addition, little is known about these behaviors and the
      underlying neural mechanisms in a genetically tractable vertebrate, the zebrafish
      Danio rerio. Using a conditioned place preference paradigm, we demonstrate that
      wildtype zebrafish exhibit a robust preference for food as well as the opiate
      drug morphine that can be blocked by the opioid receptor antagonist naloxone.
      Moreover, we show that the too few mutant, which disrupts a conserved zinc finger
      containing gene and exhibits a reduction of selective groups of dopaminergic and
      serotonergic neurons in the basal diencephalon, displays normal food preference
      but shows no preference for morphine. Pretreatment with dopamine receptor
      antagonists abolishes morphine preference in the wildtype. These studies
      demonstrate that zebrafish display measurable preference behavior for reward and
      show that the preference for natural reward and addictive drug is dissociable by
      a single-gene mutation that alters subregions of brain monoamine neurotransmitter
      systems. Future genetic analysis in zebrafish shall uncover further molecular and
      cellular mechanisms underlying the formation and function of neural circuitry
      that regulate opiate and food preference behavior.

PMID- 17010097
TI  - Sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone: a
      quantitative trait locus study of common genetic influence.
AB  - Previous studies have suggested that common genetic mechanisms influence
      sensitivity to the locomotor-stimulant effects of ethanol and allopregnanolone.
      We conducted two quantitative trait locus (QTL) studies to identify chromosomal
      regions that harbor genes that influence locomotor response to ethanol (2 g/kg)
      and allopregnanolone (17 mg/kg) using F2 crosses between C57BL/6J and DBA/2J
      mice. Because our previous data from the BXD recombinant inbred strains had
      indicated that chromosome 2 contained QTL for sensitivity to the locomotor
      stimulant effects of both ethanol and allopregnanolone, we also tested reciprocal
      chromosome 2 congenic strains for sensitivity to the locomotor-stimulant effects
      of both drugs. The F2 analysis for ethanol sensitivity identified significant QTL
      on chromosomes 1 and 2 and suggestive QTL on chromosomes 5 and 9. The analysis of
      the allopregnanolone F2 study identified suggestive QTL on chromosomes 3, 5 and
      12. Suggestive evidence for a female-specific QTL on chromosome 2 was also found.
      The studies of congenic mouse strains indicated that both the congenic strains
      captured one or more QTL for sensitivity to the locomotor-stimulant effects of
      both ethanol (2 g/kg) and allopregnanolone (17 mg/kg). When Fisher's method was
      used to combine the P values for the RI, F2 and congenic studies of the
      chromosome 2 QTL, cumulative probability scores of 9.6 x 10(-15) for ethanol and
      7.7 x 10(-7) for allopregnanolone were obtained. These results confirm the
      presence of QTL for ethanol and allopregnanolone sensitivity in a common region
      of chromosome 2 and suggest possible pleiotropic genetic influence on sensitivity
      to these drugs.

PMID- 17010098
TI  - Genetic and environmental interactions determine seizure susceptibility in
      epileptic EL mice.
AB  - Gene identification has progressed rapidly for monogenic epilepsies, but complex
      gene-environmental interactions have hindered progress in gene identification for
      multifactorial epilepsies. We analyzed the role of environmental risk factors in
      the inheritance of multifactorial idiopathic generalized epilepsy in the EL
      mouse. Seizure susceptibility was evaluated in the EL (E) and seizure-resistant
      ABP/LeJ (A) parental mouse strains and in their AEF1 and AEF2 hybrid offspring
      using a handling-induced seizure test. The seizure test was administered in three
      environments (environments I, II and III) that differed with respect to the
      number of seizure tests administered (one test or four tests) and the age of the
      mice when tested (young or old). The inheritance of seizure susceptibility
      appeared dominant after repetitive seizure testing in young or old mice, but
      recessive after a single test in old mice. Heritability was high (0.67-0.77) in
      each environment. Significant quantitative trait loci (QTL) that were associated
      with environments I and III (repetitive testing) were found on chromosomes 2 and
      9 and colocalized with previously mapped El2 and El4, respectively. The El2 QTL
      found in environment I associated only with female susceptibility. A novel QTL,
      El-N, for age-dependent predisposition to seizures was found on proximal
      chromosome 9 only in environment II. The findings indicate that environmental
      risk factors determine the genetic architecture of seizure susceptibility in EL
      mice and suggest that QTL for complex epilepsies should be defined in terms of
      the environment in which they are expressed.

PMID- 17010099
TI  - Involvement of estrogen receptor alpha, beta and oxytocin in social
      discrimination: A detailed behavioral analysis with knockout female mice.
AB  - Social recognition, processing, and retaining information about conspecific
      individuals is crucial for the development of normal social relationships. The
      neuropeptide oxytocin (OT) is necessary for social recognition in male and female
      mice, with its effects being modulated by estrogens in females. In previous
      studies, mice whose genes for the estrogen receptor-alpha (alpha-ERKO) and
      estrogen receptor-beta (beta-ERKO) as well as OTKO were knocked out failed to
      habituate to a repeatedly presented conspecific and to dishabituate when the
      familiar mouse is replaced by a novel animal (Choleris et al. 2003, Proc Natl
      Acad Sci USA 100, 6192-6197). However, a binary social discrimination assay,
      where animals are given a simultaneous choice between a familiar and a previously
      unknown individual, offers a more direct test of social recognition. Here, we
      used alpha-ERKO, beta-ERKO, and OTKO female mice in the binary social
      discrimination paradigm. Differently from their wild-type controls, when given a
      choice, the KO mice showed either reduced (beta-ERKO) or completely impaired
      (OTKO and alpha-ERKO) social discrimination. Detailed behavioral analyses
      indicate that all of the KO mice have reduced anxiety-related stretched
      approaches to the social stimulus with no overall impairment in horizontal and
      vertical activity, non-social investigation, and various other behaviors such as,
      self-grooming, digging, and inactivity. Therefore, the OT, ER-alpha, and ER-beta
      genes are necessary, to different degrees, for social discrimination and, thus,
      for the modulation of social behavior (e.g. aggression, affiliation).

PMID- 17010100
TI  - Phosphodiesterase 1B differentially modulates the effects of methamphetamine on
      locomotor activity and spatial learning through DARPP32-dependent pathways:
      evidence from PDE1B-DARPP32 double-knockout mice.
AB  - Mice lacking phosphodiesterase 1B (PDE1B) exhibit an exaggerated locomotor
      response to D-methamphetamine and increased in vitro phosphorylation of DARPP32
      (dopamine- and cAMP-regulated phosphoprotein, M r 32 kDa) at Thr34 in striatal
      brain slices treated with the D1 receptor agonist, SKF81297. These results
      indicated a possible regulatory role for PDE1B in pathways involving DARPP32.
      Here, we generated PDE1B x DARPP32 double-knockout (double-KO) mice to test the
      role of PDE1B in DARPP32-dependent pathways in vivo. Analysis of the response to
      d-methamphetamine on locomotor activity showed that the hyperactivity experienced
      by PDE1B mutant mice was blocked in PDE1B-/- x DARPP32-/- double-KO mice,
      consistent with participation of PDE1B and DARPP32 in the same pathway. Further
      behavioral testing in the elevated zero-maze revealed that DARPP32-/- mice showed
      a less anxious phenotype that was nullified in double-mutant mice. In contrast,
      in the Morris water maze, double-KO mice showed deficits in spatial reversal
      learning not observed in either single mutant compared with wild-type mice. The
      data suggest a role for PDE1B in locomotor responses to psychostimulants through
      modulation of DARPP32-dependent pathways; however, this modulation does not
      necessarily impact other behaviors, such as anxiety or learning. Instead, the
      phenotype of double-KOs observed in these latter tasks may be mediated through
      independent pathways.

PMID- 17010101
TI  - Cholinergic cells in the nucleus basalis of mice express the N-methyl-D-aspartate
      receptor subunit NR2C and its replacement by the NR2B subunit enhances frontal
      and amygdaloid acetylcholine levels.
AB  - It is known that glutamatergic and cholinergic systems interact functionally at
      the level of the cholinergic basal forebrain. The N-methyl-d-aspartate receptor
      (NMDA-R) is a multiprotein complex composed of NR1, NR2 and/or NR3 subunits. The
      subunit composition of NMDA-R of cholinergic cells in the nucleus basalis has not
      yet been investigated. Here, by means of choline acetyl transferase and NR2B or
      NR2C double staining, we demonstrate that mice express both the NR2C and NR2B
      subunits in nucleus basalis cholinergic cells. We generated NR2C-2B mutant mice
      in which an insertion of NR2B cDNA into the gene locus of the NR2C gene replaced
      NR2C by NR2B expression throughout the brain. This NR2C-2B mutant was used to
      examine whether a subunit exchange in cholinergic neurons would affect
      acetylcholine (ACh) content in several brain structures. We found increased ACh
      levels in the frontal cortex and amygdala in the brains of NR2C-2B mutant mice.
      Brain ACh has been implicated in neuroplasticity, novelty-induced arousal and
      encoding of novel stimuli. We therefore assessed behavioral habituation to novel
      environments and objects as well as object recognition in NR2C-2B subunit
      exchange mice. The behavioral analysis did not indicate any gross behavioral
      alteration in the mutant mice compared with the wildtype mice. Our results show
      that the NR2C by NR2B subunit exchange in mice affects ACh content in two target
      areas of the nucleus basalis.

PMID- 17010102
TI  - Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and
      clopidogrel in healthy human subjects.
AB  - AIMS: Ginkgo biloba is available as an over-the-counter drug and reported to
      cause haemorrhage when coadministered with other antiplatelet agents. We set out
      to study the interactions of G. biloba with cilostazol and clopidogrel. METHODS:
      A randomized, open-label, crossover study of 10 healthy male volunteers. The
      dosage schedules were 120 mg G. biloba, 240 mg G. biloba, 100 mg cilostazol, 200
      mg cilostazol, 75 mg clopidogrel, 150 mg clopidogrel, 120 mg G. biloba+ 100 mg
      cilostazol and 120 mg G. biloba+ 75 mg clopidogrel. Platelet aggregation,
      platelet count, bleeding time and clotting time were measured 0 and 6 h after
      drug administration. Platelet aggregation was performed using a dual channel
      aggregometer, by the turbimetric technique using adenosine diphosphate 5 micromol
      and 10 micromol, and collagen 1 microg ml(-1). RESULTS: Platelet inhibition with
      the combination of G. biloba and clopidogrel or cilostazol was not statistically
      significant compared with individual doses of drugs, with all the three
      aggregants. There was significant (P < 0.05) potentiation of prolongation of
      bleeding time with the combination of cilostazol and G. biloba compared with
      individual doses of both the drugs. There was no significant change in clotting
      time and platelet count. CONCLUSIONS: Coadministration of G. biloba either with
      cilostazol or clopidogrel did not enhance antiplatelet activity compared with
      individual agents. Ginkgo biloba potentiated the bleeding time prolongation
      effect of cilostazol. There was no significant correlation between prolongation
      of bleeding time and inhibition of platelet aggregation.

PMID- 17010103
TI  - The effect of St John's wort extracts on CYP3A: a systematic review of
      prospective clinical trials.
AB  - AIM: The aim of this systematic review was to assess the quality and outcomes of
      clinical trials investigating the effect of St John's wort extracts on the
      metabolism of drugs by CYP3A. METHODS: Prospective clinical trials assessing the
      effect of St John's wort (SJW) extracts on metabolism by CYP3A were identified
      through computer-based searches (from their inception to May 2005) of Medline,
      Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of
      bibliographies of relevant papers and consultation with manufacturers and
      researchers in the field. Two reviewers selected trials for inclusion,
      independently extracted data and recorded details on study design. RESULTS:
      Thirty-one studies met the eligibility criteria. More than two-thirds of the
      studies employed a before-and-after design, less than one-third of the studies
      used a crossover design, and only three studies were double-blind and placebo
      controlled. In 12 studies the SJW extract had been assayed, and 14 studies stated
      the specific SJW extract used. Results from 26 studies, including all of the 19
      studies that used high-dose hyperforin extracts (>10 mg day(-1)), had outcomes
      consistent with CYP3A induction. The three studies using low-dose hyperforin
      extracts (<4 mg day(-1)) demonstrated no significant effect on CYP3A. CONCLUSION:
      There is reasonable evidence to suggest that high-dose hyperforin SJW extracts
      induce CYP3A. More studies are required to determine whether decreased CYP3A
      induction occurs after low-dose hyperforin extracts. Future studies should adopt
      study designs with a control phase or control group, identify the specific SJW
      extract employed and provide quantitative analyses of key constituents.

PMID- 17010104
TI  - Cancer specific Mucin-1 glycoforms are expressed on multiple myeloma.
AB  - Present therapies cannot cure the large majority of patients with multiple
      myeloma (MM) and therefore new treatment strategies are imperative. This study
      analysed the different glycosylation profiles of Mucin-1 (MUC1) on MM and acute
      myeloid leukaemia (AML) cells using a series of anti-MUC1 antibodies. Seventy
      three per cent of the MM patients had plasma cells that expressed the fully
      glycosylated forms of MUC1. In contrast to controls, normal bone marrow cells and
      AML cells, the differentiation-dependent and cancer-associated glycoforms of MUC1
      were present on 59% and 36% MM tumour cells respectively. This indicated that
      aberrantly glycosylated MUC1 is a potential immunotherapeutic target in MM
      patients.

PMID- 17010105
TI  - Rapid immune reconstitution after a reduced-intensity conditioning regimen and a
      CD3-depleted haploidentical stem cell graft for paediatric refractory
      haematological malignancies.
AB  - The main obstacles to successful haploidentical haematopoietic stem cell
      transplantation from a mismatched family member donor are delayed immune
      reconstitution, vulnerability to infections and severe graft-versus-host disease
      (GvHD). We designed a reduced-intensity conditioning regimen that excluded total
      body irradiation and anti-thymocyte globulin in order to expedite immune
      reconstitution after a CD3-depleted haploidentical stem cell transplant. This
      protocol was used to treat 22 paediatric patients with refractory haematological
      malignancies. After transplantation, 91% of the patients achieved full donor
      chimaerism. They also showed rapid recovery of CD3(+) T-cells, T-cell receptor
      (TCR) excision circle counts, TCRbeta repertoire diversity and natural killer
      (NK)-cells during the first 4 months post-transplantation, compared with those
      results from a group of patients treated with a myeloablative conditioning
      regimen. The incidence and extent of viremia were limited and no lethal infection
      was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had
      grade 1 and another 27% had grade 2 acute GvHD. This well-tolerated regimen
      appears to accelerate immune recovery and shorten the duration of early post
      transplant immunodeficiency, thereby reducing susceptibility to viral infections.
      Rapid T-cell reconstitution, retention of NK-cells in the graft and induction of
      low grade GvHD may also enhance the potential anti-cancer immune effect.

PMID- 17010106
TI  - Immunogenicity of synthetic saccharide fragments of Vibrio cholerae O1 (Ogawa and
      Inaba) bound to Exotoxin A.
AB  - Recombinant exotoxin A (rEPA) from Pseudomonas aeruginosa conjugated to Vibrio
      cholerae O1 serotype-specific polysaccharides (mono-, di- and hexasaccharide)
      were immunogenic in mice. Monosaccharide conjugates boosted the humoral responses
      to the hexasaccharide conjugates. Prior exposure to purified Ogawa
      lipopolysaccharide (LPS) enabled contra-serotype hexasaccharide conjugates to
      boost the vibriocidal response, but Inaba LPS did not prime for an enhanced
      vibriocidal response by a contra-serotype conjugate. Prior exposure to the
      carrier, and priming B cells with the LPS of either serotype, resulted in
      enhanced vibriocidal titers if the Ogawa hexasaccharides were used, but a
      diminished response to the Inaba LPS. These studies demonstrate that the
      'functional' B cell epitopes on the LPS differ from those of the
      neoglycoconjugates and that the order of immunization and the serotype of the
      boosting conjugate can influence the epitope specificity and function of the
      antisera.

PMID- 17010107
TI  - Spatial and temporal expression patterns of Avr1b-1 and defense-related genes in
      soybean plants upon infection with Phytophthora sojae.
AB  - The Avr1b locus is required for avirulence of the oomycete pathogen Phytophthora
      sojae on soybeans carrying resistance gene Rps1b. One of the Avr genes of the
      locus (Avr1b-1) was shown to encode an elicitor. We have analyzed the spatial and
      temporal expression patterns of Avr1b-1 in comparison to defense-related genes
      induced in soybean. Avr1b-1 expression was detectable mainly in close proximity
      to the site of infection, in wound-inoculated hypocotyls as well as in roots
      infected with zoospores. Usually, in compatible interactions, higher expression
      levels of Avr1b-1 were observed in roots when compared with incompatible P. sojae
      soybean interactions, whereas neither the timing nor the amount of transcript
      accumulation of defense-related genes showed cultivar-specific differences. In
      contrast, the PsojNIP gene encoding a proposed virulence factor was expressed
      only during the necrotrophic phase in the compatible interaction.

PMID- 17010108
TI  - Reduced myocarditis following Coxsackievirus infection in cellular FLICE
      inhibitory protein--long form-transgenic mice.
AB  - Cellular FLICE inhibitory protein--long form (c-FLIP(L)) is a caspase-defective
      homologue of caspase-8 that blocks apoptosis by death receptors. c-FLIP(L)
      expression in T cells can also augment activation of the mitogen-activated
      protein kinase, extracellular signal-related kinase, as well as nuclear factor
      kappaB. This contributes to increased production of interleukin-2 and CD25,
      resulting in hyperproliferation of T cells from c-FLIP(L)-transgenic mice. c-FLIP
      also heterodimerizes with and activates caspase-8, resulting in increased death
      of T cells and a selection of a T helper 2 cytokine profile. The effects of c
      FLIP on cytolytic function of CD8(+) T cells have not been examined previously.
      We studied the cytolytic capacity of T cells from c-FLIP(L)-transgenic mice using
      an antigen-specific system, as well as the consequences during a viral immune
      response to Coxsackievirus B3 (CVB3). The increased T-cell receptor (TCR)
      signalling due to c-FLIP did not alter the cytolytic machinery but did reduce
      cytotoxicity because of decreased surface expression of TCR and CD8. It also
      produced a Tc2 cytokine profile. These effects of c-FLIP collectively served to
      diminish the severity of CVB3-induced myocarditis.

PMID- 17010110
TI  - The maize Mucronate mutation is a deletion in the 16-kDa gamma-zein gene that
      induces the unfolded protein response.
AB  - Mucronate (Mc) was identified as a dominant maize (Zea mays L.) opaque kernel
      mutation that alters zein storage protein synthesis. Zein protein bodies in Mc
      endosperm are misshapen and are associated with increased levels of ER Lumenal
      Binding Protein (BiP). Using GeneCalling to profile endosperm RNA transcripts, we
      identified an aberrant RNA in Mc that encodes the 16-kDa gamma-zein protein. The
      transcript contains a 38-bp deletion (nucleotides 406-444 after the initiation
      codon) that creates a frame-shift mutation and an abnormal sequence for the last
      63 amino acids. Genetic mapping revealed the Mc mutation is linked with the locus
      encoding the 16-kDa gamma-zein, and two-dimensional gel electrophoresis confirmed
      the 16-kDa gamma-zein protein is altered in Mc. The mutant protein exhibited
      changes in solubility properties and co-immunoprecipitated with the molecular
      chaperone, BiP. Transgenic maize plants expressing the Mc 16-kDa gamma-zein
      manifested an opaque kernel phenotype with enhanced levels of BiP in the
      endosperm, similar to the Mc mutant. Unlike the wild-type protein, the Mc 16-kDa
      gamma-zein interacted only weakly with the 22-kDa alpha-zein when expressed in
      the yeast two-hybrid system. These results indicate that the Mc phenotype results
      from a frame-shift mutation in the gene encoding the 16-kDa gamma-zein protein,
      leading to the unfolded protein response in developing endosperm.

PMID- 17010111
TI  - Identification of plant cytoskeleton-interacting proteins by screening for actin
      stress fiber association in mammalian fibroblasts.
AB  - Taking advantage of the high conservation of the cytoskeleton building blocks
      actin and tubulin between plant and animal kingdoms, we developed a functional
      genomic screen for the isolation of new plant cytoskeleton-binding proteins that
      uses a mammalian cell expression system. A yellow fluorescent protein (YFP)
      fusion cDNA library from Arabidopsis was inserted into rat fibroblasts and
      screened for fluorescent chimeras localizing to cytoskeletal structures. The high
      throughput screen was performed by an automated microscope. An initial set of
      candidate genes identified in the screen was isolated, sequenced, the full-length
      cDNAs were synthesized by RT-PCR and tested by biochemical approaches to verify
      the ability of the genes to bind actin directly. Alternatively, indirect binding
      via interaction with other actin-binding proteins was studied. The full-length
      cDNAs were transferred back to plants as YFP chimeras behind the CAMV-35S
      promoter. We give here two examples of new plant cytoskeletal proteins identified
      in the pilot screen. ERD10, a member of the dehydrin family of proteins, was
      localized to actin stress fibers in rat fibroblasts. Its direct binding to actin
      filaments was confirmed by several biochemical approaches. Touch-induced
      calmodulin-like protein, TCH2, was also localized to actin stress fibers in
      fibroblasts, but was unable to bind actin filaments directly in vitro.
      Nevertheless, it did bind to the IQ domains of Arabidopsis myosin VIII in a
      calcium-dependent manner. Further evidence for a cytoskeletal function of ERD10
      was obtained in planta; GFP-ERD10 was able to protect the actin cytoskeleton from
      latrunculin-mediated disruption in Nicotiana benthamiana leaves.

PMID- 17010112
TI  - PICKLE is required for SOLITARY-ROOT/IAA14-mediated repression of ARF7 and ARF19
      activity during Arabidopsis lateral root initiation.
AB  - Lateral root (LR) formation in Arabidopsis is regulated by auxin signaling
      through AUXIN RESPONSE FACTOR transcriptional activators, ARF7 and ARF19, and
      auxin/indole-3-acetic acid (Aux/IAA) repressors, including SOLITARY-ROOT
      (SLR)/IAA14. Previous studies have strongly suggested that, in the gain-of
      function slr-1 mutant, stabilized mutant IAA14 (mIAA14) protein inactivates
      ARF7/19 functions, thereby completely blocking LR initiation. However, the
      mechanism of inactivation is still unknown. We have now identified an extragenic
      suppressor mutation of slr-1, suppressor of slr2 (ssl2), which specifically
      restores LR formation in the slr-1 mutant, and have found that SSL2 negatively
      regulates the auxin-induced pericycle cell divisions required for LR initiation.
      The SSL2 gene encodes PICKLE (PKL), a homologue of the animal chromatin
      remodeling factor CHD3/Mi-2, and LR formation restored in pkl/ssl2 slr-1 mutants
      depends on ARF7/19 functions, suggesting that ARF7/19-dependent transcription
      takes place if there is a pkl/ssl2 mutation in slr-1. In animals, Mi-2 represses
      transcription as a subunit of the NuRD/Mi-2 complex containing histone
      deacetylases (HDACs). Inhibition of HDAC activity by trichostatin A also results
      in LR formation in the slr-1 mutant, but not in the slr-1 arf7 arf19 triple
      mutant, suggesting that normal HDAC activity is required for the mIAA14-mediated
      inactivation of ARF7/19 functions in LR initiation. Taken together, our data
      suggest that PKL/SSL2-mediated chromatin remodeling negatively regulates auxin
      mediated LR formation in Arabidopsis.

PMID- 17010113
TI  - Regulation of hormone metabolism in Arabidopsis seeds: phytochrome regulation of
      abscisic acid metabolism and abscisic acid regulation of gibberellin metabolism.
AB  - In a wide range of plant species, seed germination is regulated antagonistically
      by two plant hormones, abscisic acid (ABA) and gibberellin (GA). In the present
      study, we have revealed that ABA metabolism (both biosynthesis and inactivation)
      was phytochrome-regulated in an opposite fashion to GA metabolism during
      photoreversible seed germination in Arabidopsis. Endogenous ABA levels were
      decreased by irradiation with a red (R) light pulse in dark-imbibed seeds pre
      treated with a far-red (FR) light pulse, and the reduction in ABA levels in
      response to R light was inhibited in a phytochrome B (PHYB)-deficient mutant.
      Expression of an ABA biosynthesis gene, AtNCED6, and the inactivation gene,
      CYP707A2, was regulated in a photoreversible manner, suggesting a key role for
      the genes in PHYB-mediated regulation of ABA metabolism. Abscisic acid-deficient
      mutants such as nced6-1, aba2-2 and aao3-4 exhibited an enhanced ability to
      germinate relative to wild type when imbibed in the dark after irradiation with
      an FR light pulse. In addition, the ability to synthesize GA was improved in the
      aba2-2 mutant compared with wild type during dark-imbibition after an FR light
      pulse. Activation of GA biosynthesis in the aba2-2 mutant was also observed
      during seed development. These data indicate that ABA is involved in the
      suppression of GA biosynthesis in both imbibed and developing seeds. Spatial
      expression patterns of the AtABA2 and AAO3 genes, responsible for last two steps
      of ABA biosynthesis, were distinct from that of the GA biosynthesis gene,
      AtGA3ox2, in both imbibed and developing seeds, suggesting that biosynthesis of
      ABA and GA in seeds occurs in different cell types.

PMID- 17010114
TI  - Tobacco aquaporin NtAQP1 is involved in mesophyll conductance to CO2 in vivo.
AB  - Leaf mesophyll conductance to CO(2) (g(m)) has been recognized to be finite and
      variable, rapidly adapting to environmental conditions. The physiological basis
      for fast changes in g(m) is poorly understood, but current reports suggest the
      involvement of protein-facilitated CO(2) diffusion across cell membranes. A good
      candidate for this could be the Nicotiana tabacum L. aquaporin NtAQP1, which was
      shown to increase membrane permeability to CO(2) in Xenopus oocytes. The
      objective of the present work was to evaluate its effect on the in vivo mesophyll
      conductance to CO(2), using plants either deficient in or overexpressing NtAQP1.
      Antisense plants deficient in NtAQP1 (AS) and NtAQP1 overexpressing tobacco
      plants (O) were compared with their respective wild-type (WT) genotypes (CAS and
      CO). Plants grown under optimum conditions showed different photosynthetic rates
      at saturating light, with a decrease of 13% in AS and an increase of 20% in O,
      compared with their respective controls. CO(2) response curves of photosynthesis
      also showed significant differences among genotypes. However, in vitro analysis
      demonstrated that these differences could not be attributed to alterations in
      Rubisco activity or ribulose-1,5-bisphosphate content. Analyses of chlorophyll
      fluorescence and on-line (13)C discrimination indicated that the observed
      differences in net photosynthesis (A(N)) among genotypes were due to different
      leaf mesophyll conductances to CO(2), which was estimated to be 30% lower in AS
      and 20% higher in O compared with their respective WT. These results provide
      evidence for the in vivo involvement of aquaporin NtAQP1 in mesophyll conductance
      to CO(2).

PMID- 17010109
TI  - Characterizing the composition and evolution of homoeologous genomes in hexaploid
      wheat through BAC-end sequencing on chromosome 3B.
AB  - Bread wheat (Triticum aestivum) is one of the most important crops worldwide.
      However, because of its large, hexaploid, highly repetitive genome it is a
      challenge to develop efficient means for molecular analysis and genetic
      improvement in wheat. To better understand the composition and molecular
      evolution of the hexaploid wheat homoeologous genomes and to evaluate the
      potential of BAC-end sequences (BES) for marker development, we have followed a
      chromosome-specific strategy and generated 11 Mb of random BES from chromosome
      3B, the largest chromosome of bread wheat. The sequence consisted of about 86% of
      repetitive elements, 1.2% of coding regions, and 13% remained unknown. With 1.2%
      of the sequence length corresponding to coding sequences, 6000 genes were
      estimated for chromosome 3B. New repetitive sequences were identified, including
      a Triticineae-specific tandem repeat (Fat) that represents 0.6% of the B-genome
      and has been differentially amplified in the homoeologous genomes before
      polyploidization. About 10% of the BES contained junctions between nested
      transposable elements that were used to develop chromosome-specific markers for
      physical and genetic mapping. Finally, sequence comparison with 2.9 Mb of random
      sequences from the D-genome of Aegilops tauschii suggested that the larger size
      of the B-genome is due to a higher content in repetitive elements. It also
      indicated which families of transposable elements are mostly responsible for
      differential expansion of the homoeologous wheat genomes during evolution. Our
      data demonstrate that BAC-end sequencing from flow-sorted chromosomes is a
      powerful tool for analysing the structure and evolution of polyploid and highly
      repetitive genomes.

PMID- 17010115
TI  - Cluster randomised trial of an active, multifaceted educational intervention
      based on the WHO Reproductive Health Library to improve obstetric practices.
AB  - OBJECTIVE: We conducted a trial to evaluate the effect of an active, multifaceted
      educational strategy to promote the use of the WHO Reproductive Health Library
      (RHL) on obstetric practices. DESIGN: Cluster randomised trial. The trial was
      assigned the International Standardised Randomised Controlled Trial Number
      ISRCTN14055385. SETTINGS: Twenty-two hospitals in Mexico City and 18 in the
      Northeast region of Thailand. METHODS: The intervention consisted primarily of
      three interactive workshops using RHL over a period of 6 months. The focus of the
      workshops was to provide access to knowledge and enable its use. A computer and
      support for using both the computer and RHL were provided at each hospital. The
      control hospitals did not receive any intervention. MAIN OUTCOME MEASURES: The
      main outcome measures were changes in ten selected clinical practices as
      recommended in RHL starting approximately four to six months after the third
      workshop. Clinical practice data were collected at each hospital from 1000
      consecutively delivered women or for a 6-month period whichever was reached
      sooner. RESULTS: The active, multifaceted educational intervention we employed
      did not affect the ten targeted practices in a consistent and substantive way.
      Iron/folate supplementation, uterotonic use after birth and breastfeeding on
      demand were already frequently practiced, and we were unable to measure external
      cephalic version. Of the remaining six practices, selective, as opposed to
      routine episiotomy policy increased in the intervention group (difference in
      adjusted mean rate = 5.3%; 95% CI -0.1 to 10.7%) in Thailand, and there was a
      trend towards an increased use of antibiotics at caesarean section in Mexico
      (difference in adjusted mean rate = 19.0%; 95% CI: -8.0 to 46.0%). There were no
      differences in the use of labour companionship, magnesium sulphate use for
      eclampsia, corticosteroids for women delivering before 34 weeks and vacuum
      extraction. RHL awareness (24.8-65.5% in Mexico and 33.9-83.3% in Thailand) and
      use (4.8-34.9% in Mexico and 15.5-76.4% in Thailand) increased substantially
      after the intervention in both countries. CONCLUSION: The multifaceted, active
      strategy to provide health workers with the knowledge and skills to use RHL to
      improve their practice led to increased access to and use of RHL, however, no
      consistent or substantive changes in clinical practices were detected within 4-6
      months after the third workshop.

PMID- 17010116
TI  - Association between lactate in vaginal fluid and time to spontaneous onset of
      labour for women with suspected prelabour rupture of the membranes.
AB  - OBJECTIVES: To assess whether lactate determination in vaginal fluid is
      associated with, and can predict, onset of labour for women with suspected
      prelabour rupture of the membranes (PROM). DESIGN: Prospective observational
      study. SETTING: Labour ward at Soder Hospital, Stockholm, Sweden. POPULATION:
      Women with suspected PROM after 34 weeks of gestation, who later had spontaneous
      onset of labour (n = 179). METHODS: All women underwent a speculum examination
      and a test for determining lactate concentration in vaginal fluid. We used
      logistic regression to estimate the association between lactate concentration in
      vaginal fluid and time to onset of labour. MAIN OUTCOME MEASURES: Time from
      examination to onset of labour (cervix > or =4 cm), within 24 hours and 48 hours.
      RESULTS: The median time interval between examination and spontaneous onset of
      labour was 8.4 hours for women with 'high' lactate (> or =4.5 mmol/l) and 54
      hours for those with 'low' lactate concentrations (<4.5 mmol/l). Among 86 women
      with high lactate concentrations, 76 (88%) had started labour within 24 hours
      compared with 20 of 93 (22%) women with low lactate concentrations (OR 27.7, 95%
      CI 12.2-63.3). After checking for the effect of visible amniotic fluid, the
      corresponding odds were still substantially increased (OR 13.5, 95% CI 5.3-34.3).
      CONCLUSIONS: High lactate concentration (> or =4.5 mmol/l) in vaginal fluid can
      be used to predict whether a woman with suspected PROM will commence spontaneous
      onset of labour within 24 or 48 hours.

PMID- 17010117
TI  - Bacterial vaginosis in a cohort of Danish pregnant women: prevalence and
      relationship with preterm delivery, low birthweight and perinatal infections.
AB  - OBJECTIVE: To determine the prevalence of bacterial vaginosis (BV) in the second
      trimester of pregnancy in a Danish population using the Schmidt criteria and to
      examine whether BV was associated with subsequent preterm delivery, low
      birthweight or perinatal infections. DESIGN: Prospective cohort study. SETTING:
      Department of Obstetrics and Gynaecology at a University Hospital, Denmark.
      POPULATION: Three thousand five hundred and forty pregnant women aged 18 years or
      more. METHODS: A smear from the vagina was obtained from all women, air-dried and
      stored for subsequent diagnosis of BV. After rehydration with isotonic saline,
      the smear was examined in a phase-contrast microscope at 400x, and the numbers of
      lactobacilli morphotypes and small bacterial morphotypes were counted. A score
      for BV was calculated according to the method described by Schmidt. The outcome
      of pregnancy from 20 weeks of gestation was examined in the 3262 singleton
      pregnant women who were included in this study before 20 weeks of gestation. The
      relationship between BV and adverse outcome of pregnancy was examined by
      univariate and multivariate analyses. MAIN OUTCOME MEASURES: Prevalence of BV,
      preterm delivery (<37 weeks), low birthweight (<2500 g), preterm delivery of a
      low-birthweight infant and clinical chorioamnionitis. RESULTS: The prevalence of
      BV was 16%, and the rate of preterm delivery was 5.2% in the study population of
      3262 singleton pregnant women who were included before 20 weeks of gestation.
      Mean birthweight was significantly lower in infants of women with BV than in
      infants of women without BV (3408 versus 3511 g, P < 0.01). Univariate analyses
      showed that BV was marginally associated with preterm delivery but significantly
      associated with low birthweight, preterm delivery of a low birthweight infant,
      indicated preterm delivery and clinical chorioamnionitis. Multivariate analyses,
      which adjusted for previous miscarriage, previous preterm delivery, previous
      conisation, smoking, gestational diabetes, fetal death and preterm premature
      rupture of membranes, showed that BV was significantly associated with low
      birthweight (OR 1.95, 95% CI 1.3-2.9), preterm delivery of a low-birthweight
      infant (OR 2.5, 95% CI 1.6-3.9), indicated preterm delivery (OR 2.4, 95% CI 1.4
      4.1) and clinical chorioamnionitis (OR 2.7, 95% CI 1.4-5.1). CONCLUSIONS: The
      prevalence of BV determined using the Schmidt criteria in the early second
      trimester of pregnancy was similar to that found in similar studies. The presence
      of BV before 20 weeks of gestation was an independent risk factor for delivery of
      an infant with low birthweight, preterm delivery of a low-birthweight infant,
      indicated preterm delivery and clinical chorioamnionitis.

PMID- 17010118
TI  - Adiponectin and insulin resistance in early- and late-onset pre-eclampsia.
AB  - OBJECTIVE: To evaluate the importance of adiponectin and insulin resistance in
      early- and late-onset pre-eclampsia. DESIGN: A nested case-control study in 72
      pregnant women who participated in the first-trimester Down-syndrome-screening
      programme and who delivered at our hospital. SETTING: University Hospital,
      Department of Obstetrics and Gynecology. POPULATION: Pregnant women: 36 women
      with pre-eclampsia of which 20 late onset and 16 early onset were compared with
      36 uncomplicated pregnancies who delivered at term. METHODS: In all the women,
      insulin resistance was calculated by the homeostasis model assessment ratio (HOMA
      IR) and plasma adiponectin was determined using an enzyme-linked immunosorbent
      assay. MAIN OUTCOME MEASURES: Insulin resistance and adiponectin concentration.
      RESULTS: First-trimester plasma adiponectin mean levels in the whole pre
      eclampsia group were significantly lower than that in the control group (8.4 +/-
      3.3 versus 14.8 +/- 4.6 microgram/ml; P < 0.001), whereas first-trimester mean
      HOMA-IR values were significantly higher in the pre-eclampsia group than that in
      the control group (2.0 +/- 1.1 versus 1.0 +/- 0.4; P= 0.01). Plasma adiponectin
      concentrations at delivery in the pre-eclampsia group were significantly higher
      than that in the control group (9.2 +/- 3.7 versus 7.8 +/- 2.6 microgram/ml; P=
      0.04). First-trimester plasma adiponectin mean concentrations in the late-onset
      subgroup were significantly lower compared with the concentrations in early-onset
      subgroup (6.2 +/- 1.4 microgram/ml versus 11.1 +/- 3.2 microgram/ml; P < 0.001),
      and there was a significant difference in adiponectin plasma values only between
      women in the late-onset pre-eclampsia group versus those in the control group (P
      < 0.001). First-trimester mean HOMA-IR values were significantly higher in the
      late-onset subgroup compared with that of the early-onset subgroup (2.5 +/- 1.3
      versus 1.3 +/- 0.3; P= 0.02), and there was a significant difference only between
      the control group versus the late-onset subgroup (P= 0.001). CONCLUSIONS: First
      trimester adiponectin and HOMA-IR values seem to select two completely different
      populations: early- and late-onset pre-eclampsia, which might suggest a different
      pathogenesis.

PMID- 17010119
TI  - Regulation of apicomplexan microfilament dynamics by a minimal set of actin
      binding proteins.
AB  - Efficient and rapid host cell invasion is a prerequisite for an intracellular
      parasitic life style. Pathogens typically induce receptor-mediated endocytosis
      and hijack the force-transducing system of a host cell to gain access to a
      replication-competent niche. In striking contrast, apicomplexan parasites such as
      Plasmodium, the causative agent of malaria, and the human and animal pathogens
      Toxoplasma and Cryptosporidium employ their own actomyosin motor machinery to
      propel themselves into prospective host cells. Understanding the regulation and
      dynamics of actin-based motility of these parasites is therefore central to
      understanding their pathogenesis. The parasite genomes harbour surprisingly few
      potential actin-regulatory proteins indicating that a basic repertoire meets the
      requirements to regulate actin dynamics. In this article, we summarize our
      current knowledge of Plasmodium microfilament dynamics and describe its potential
      players.

PMID- 17010120
TI  - Cargo selectivity of the ERGIC-53/MCFD2 transport receptor complex.
AB  - Exit of soluble secretory proteins from the endoplasmic reticulum (ER) can occur
      by receptor-mediated export as exemplified by blood coagulation factors V and
      VIII. Their efficient secretion requires the membrane lectin ER Golgi
      intermediate compartment protein-53 (ERGIC-53) and its soluble luminal
      interaction partner multiple coagulation factor deficiency protein 2 (MCFD2),
      which form a cargo receptor complex in the early secretory pathway. ERGIC-53 also
      interacts with the two lysosomal glycoproteins cathepsin Z and cathepsin C. Here,
      we tested the subunit interdependence and cargo selectivity of ERGIC-53 and MCFD2
      by short interference RNA-based knockdown. In the absence of ERGIC-53, MCFD2 was
      secreted, whereas knocking down MCFD2 had no effect on the localization of ERGIC
      53. Cargo binding properties of the ERGIC-53/MCFD2 complex were analyzed in vivo
      using yellow fluorescent protein fragment complementation. We found that MCFD2 is
      dispensable for the binding of cathepsin Z and cathepsin C to ERGIC-53. The
      results indicate that ERGIC-53 can bind cargo glycoproteins in an MCFD2
      independent fashion and suggest that MCFD2 is a recruitment factor for blood
      coagulation factors V and VIII.

PMID- 17010121
TI  - Defective intracellular trafficking of uromodulin mutant isoforms.
AB  - Medullary cystic kidney disease/familial juvenile hyperuricemic nephropathy
      (MCKD/FJHN) are autosomal dominant renal disorders characterized by tubulo
      interstitial fibrosis, hyperuricemia and medullary cysts. They are caused by
      mutations in the gene encoding uromodulin, the most abundant protein in urine.
      Uromodulin (or Tamm-Horsfall protein) is a glycoprotein that is exclusively
      expressed by epithelial tubular cells of the thick ascending limb of Henle's loop
      and distal convoluted tubule. To date, 37 different uromodulin mutations have
      been described in patients with MCKD/FJHN. Interestingly, 60% of them involve one
      of the 48 conserved cysteine residues. We have previously shown that cysteine
      affecting mutations could lead to partial endoplasmic reticulum (ER) retention.
      In this study, as a further step in understanding uromodulin biology in health
      and disease, we provide the first extensive study of intracellular trafficking
      and subcellular localization of wild-type and mutant uromodulin isoforms. We
      analyzed a set of 12 different uromodulin mutations that were representative of
      the different kind of mutations identified so far by different experimental
      approaches (immunofluorescence, electron microscopy, biochemistry and in vivo
      imaging) in transiently transfected HEK293 and Madin-Darby canine kidney cells.
      We assessed protein processing in the secretory pathway and could demonstrate
      that although to different extent, all uromodulin mutations lead to defective ER
      to Golgi protein transport, suggesting a common pathogenetic mechanism in
      MCKD/FJHN.

PMID- 17010122
TI  - Cooperation of phosphoinositides and BAR domain proteins in endosomal tubulation.
AB  - Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate many
      intracellular events, including vesicular trafficking and actin remodeling, by
      recruiting proteins to their sites of function. PtdIns(4,5)-bisphosphate
      [PI(4,5)P2] and related phosphoinositides are mainly synthesized by type I PtdIns
      4-phosphate 5-kinases (PIP5Ks). We found that PIP5K induces endosomal tubules in
      COS-7 cells. ADP-ribosylation factor (ARF) 6 has been shown to act upstream of
      PIP5K and regulate endocytic transport and tubulation. ARF GAP with coiled-coil,
      ankyrin repeat, and pleckstrin homology domains 1 (ACAP1) has guanosine
      triphosphatase-activating protein (GAP) activity for ARF6. While there were few
      tubules induced by the expression of ACAP1 alone, numerous endosomal tubules were
      induced by coexpression of PIP5K and ACAP1. ACAP1 has a pleckstrin homology (PH)
      domain known to bind phosphoinositide and a Bin/amphiphysin/Rvs (BAR) domain that
      has been reported to detect membrane curvature. Truncated and point mutations in
      the ACAP1 BAR and PH domains revealed that both BAR and PH domains are required
      for tubulation. These results suggest that two ARF6 downstream molecules, PIP5K
      and ACAP1, function together in endosomal tubulation and that phosphoinositide
      levels may regulate endosomal dynamics.

PMID- 17010123
TI  - A role for adaptor protein-3 complex in the organization of the endocytic pathway
      in Dictyostelium.
AB  - Dictyostelium discoideum cells continuously internalize extracellular material,
      which accumulates in well-characterized endocytic vacuoles. In this study, we
      describe a new endocytic compartment identified by the presence of a specific
      marker, the p25 protein. This compartment presents features reminiscent of
      mammalian recycling endosomes: it is localized in the pericentrosomal region but
      distinct from the Golgi apparatus. It specifically contains surface proteins that
      are continuously endocytosed but rapidly recycled to the cell surface and thus
      absent from maturing endocytic compartments. We evaluated the importance of each
      clathrin-associated adaptor complex in establishing a compartmentalized endocytic
      system by studying the phenotype of the corresponding mutants. In knockout cells
      for mu3, a subunit of the AP-3 clathrin-associated complex, membrane proteins
      normally restricted to p25-positive endosomes were mislocalized to late endocytic
      compartments. Our results suggest that AP-3 plays an essential role in the
      compartmentalization of the endocytic pathway in Dictyostelium.

PMID- 17010129
TI  - From rats to monkeys to man-the neurophysiology of alcoholism: a tribute to Henri
      Begleiter.

PMID- 17010130
TI  - Letter to the editor in regard to Caetano, Ramisetty-Mikler, Floyd, and McGrath
      (2006): "The epidemiology of drinking among women of child-bearing age".

PMID- 17010131
TI  - Association between gene polymorphisms of SLC22A3 and methamphetamine use
      disorder.
AB  - BACKGROUND: Methamphetamine (MAP) is one of the most frequently used illegal
      substances in Japan, and family and twin studies have suggested that genetic
      factors contribute to psychostimulant dependence, including MAP dependence.
      Organic cation transporter 3 (OCT3) has been reported to be involved in the
      disposition of MAP as well as MAP-induced behavioral changes in animals.
      Moreover, SLC22A3 (which encodes OCT3) is a candidate gene for MAP dependence
      because it is located within a chromosomal region associated with substance
      dependence. METHODS: Using 96 healthy control subjects, linkage disequilibrium
      (LD) within the SLC22A3 was investigated, and 5 single-nucleotide polymorphisms
      (SNPs) were selected as haplotype tag SNPs to search for an association with MAP
      dependence. Single-marker analyses and haplotype analyses of these SNPs were
      performed in 213 subjects with MAP dependence and 443 healthy controls. RESULTS:
      SLC22A3 polymorphisms were not significantly associated with MAP dependence in
      any of the single-marker and haplotype analyses. When subjects with MAP
      dependence were divided into polysubstance and single-MAP users, genotype and
      allele frequency of SNP2 (p=0.024, p=0.011, respectively), allele frequency of
      SNP3 (p=0.037), and haplotypic frequencies for these 2 SNPs (p=0.0438) differed
      significantly between groups. CONCLUSIONS: These results suggest that
      polymorphisms of SLC22A3 are related to the development of polysubstance use in
      Japanese patients with MAP dependence.

PMID- 17010132
TI  - Monoamine metabolism and behavioral responses to ethanol in mitochondrial
      aldehyde dehydrogenase knockout mice.
AB  - BACKGROUND: It is widely accepted that, in addition to removing acetaldehyde
      produced during the metabolism of ethanol, mitochondrial aldehyde dehydrogenase
      (ALDH2) functions in the pathway by which aldehyde metabolites of the monoamines
      dopamine (DA) and serotonin (5-HT) are converted to their acidic metabolites.
      Moreover, studies of ALDH2 inhibitors used for treating alcoholism suggest that
      their antidipsotropic effects may be related to inhibition of monoamine
      metabolism. Therefore, we examined the hypothesis that altered brain monoamine
      metabolism is related to the influence of ALDH2 on behavioral responses to
      ethanol. METHODS: Mice were generated with a gene-trap mutation of the ALDH2
      gene. ALDH2 mRNA was absent in ALDH2-/- mice. Western blot analysis of liver
      mitochondria confirmed the absence of ALDH2 protein in the ALDH2-/- mice. Wild
      type and ALDH2-deficient mice were tested for the effects of different doses of
      ethanol on locomotor activity, ataxia, and a 2-bottle ethanol-water preference
      test. RESULTS: Wild-type and ALDH2+/- mice preferred ethanol to water. However,
      ALDH2-/- mice drank significantly less ethanol than wild-type or ALDH2+/- mice.
      Locomotor activity and ataxia were significantly more affected by ethanol in
      ALDH2-/- mice than in wild-type or ALDH2+/- mice. There was no effect of genotype
      on levels of 5-HT, DA, or their precursors or metabolites in several brain
      regions, as measured by HPLCec. CONCLUSIONS: The results indicate that: (1) the
      effect of the mutant genotype on behavioral responses to ethanol is unrelated to
      altered brain monoamine metabolism and (2) ALDH2 is not required for the
      metabolism of brain monoamines in vivo.

PMID- 17010133
TI  - Gene array profiles of alcohol and aldehyde metabolizing enzymes in brains of
      C57BL/6 and DBA/2 mice.
AB  - BACKGROUND: Differences in ethanol metabolizing enzymes expressed in brain have
      been suggested to contribute to the significant differences in ethanol (alcohol)
      preference between inbred C57BL/6 and DBA/2 mouse strains. METHODS: We have
      utilized 2 different platforms of oligonucleotide microarray technology (CodeLink
      UniSet I BioArray from G.E. Healthcare and MG U74A v2.0 from Affymetrix) to
      simultaneously assess expression of alcohol and acetaldehyde metabolizing enzymes
      in the whole brain of naive (no exposure to alcohol) C57BL/6 and DBA/2 mice.
      RESULTS: There were no significant differences between the 2 strains of mice in
      gene expression intensity for alcohol dehydrogenases (ADH), catalase, and a
      number of the cytochrome P450 family of genes, which can be involved in ethanol
      catabolism. However, significantly higher expression of mRNA for aldehyde
      dehydrogenase 2 (ALDH2), an isoform mainly responsible for the catabolism of
      acetaldehyde, was observed in whole brains of DBA/2 mice with both platforms.
      Aldehyde dehydrogenase 2 protein was also higher in DBA/2 brain. Expression of
      aldehyde dehydrogenase 1A1 (ALDH1A1) mRNA was found to be higher in brains of
      DBA/2 mice, when measured with the CodeLink platform, but not when measured with
      Affymetrix arrays or quantitative reverse transcriptase-real-time polymerase
      chain reaction (qRT-PCR). The ALDH1A1 protein, however, reflected the results
      obtained with the CodeLink arrays and was higher in DBA/2 brain, compared with
      brains of C57BL/6 mice. In contrast, the expression intensity for the aldehyde
      dehydrogenase 7A1 (ALDH7A1) mRNA and protein was significantly higher in C57BL/6
      mice than DBA/2 mice. These expression differences are consistent with more rapid
      metabolism of acetaldehyde in brains of DBA/2 mice. CONCLUSIONS: The use of 2
      different microarray platforms provides important cross-validation of many
      results, and some discrepancies can be resolved with qRT-PCR and immunoblotting.
      The expression differences that were validated may affect alcohol/aldehyde
      metabolism in brain and/or alcohol preference in the 2 strains of mice.

PMID- 17010134
TI  - Decision-making deficits in alcohol-dependent patients with and without comorbid
      personality disorder.
AB  - BACKGROUND: Impairments in decision making are a consistent finding in substance
      use disorder (SUD) populations. However, decision-making deficits are not
      specific for SUDs and are also reported in the context of other psychiatric
      disorders such as antisocial and borderline personality disorders (PDs). Given
      the frequent comorbidity between SUD and cluster B PD, it might be questioned
      whether the decision-making impairments typically reported in SUD populations
      reflect the addictive disorder, the cluster B PD, or a combination of the 2.
      METHODS: In the current study, we compare the decision-making performance of non
      substance-abusing controls (n=53) on the Iowa Gambling Task (IGT) with the
      decision-making performance of 3 abstinent alcohol-dependent samples, i.e.,
      alcoholic patients without any PD (n=38), alcoholic patients with a cluster A or
      C PD (n=19), and alcoholic patients with a cluster B PD (n=23). RESULTS: Overall,
      all 3 alcohol-dependent subsamples performed inferior compared with controls.
      Between alcoholic subsamples, the alcoholic patients with a cluster A or C PD had
      the highest IGT score, followed by the alcoholic patients without a PD, while the
      cluster B alcoholic patients were the most impaired. CONCLUSION: These findings
      suggest that impairments in decision making underlie both alcohol dependence and
      cluster B PD, and alcoholic patients with a comorbid cluster B PD are
      particularly impaired in their decision making. These deficits may underlie the
      severe problems that characterize cluster B alcoholic patients specifically in
      inappropriate behaviors (e.g., poly substance abuse, legal, and professional
      dysfunction).

PMID- 17010135
TI  - Individual differences in ethanol self-administration following withdrawal are
      associated with asymmetric changes in dopamine and serotonin in the medial
      prefrontal cortex and amygdala.
AB  - BACKGROUND: Ethanol withdrawal alters brain neurochemistry, causes asymmetric
      activation of neurons in the medial prefrontal cortex (mPFC) and amygdala (AMY),
      and increases ethanol craving and drinking. Rats with intrinsic rightward-turning
      preferences drink more ethanol than those with left or no preferences; they also
      exhibit an ethanol-induced neurochemical activation that favors the right side of
      the mPFC. Our experiments used rats with different turning preferences to assess
      differences in withdrawal effects on mPFC and AMY neurochemistry as well as
      ethanol self-administration. METHODS AND RESULTS: Rats with left-turning, right
      turning, and nonturning preferences were fed a 6% ethanol-containing liquid diet
      (WD) or a pair-fed control diet for 14 days. Differences in dopamine (DA),
      serotonin (5HT), norepinephrine (NE), and metabolite [3,4-dihydroxphenylacetic
      acid, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid) concentrations
      were assessed in each side of the mPFC and AMY during acute withdrawal. Similar
      groups were fed the same diets and tested for consumption of 10% ethanol versus
      water and 1% sucrose versus water. WD increased HVA/DA in the mPFC and caused
      depletions of DA and 5HT in the mPFC and 5HT in the AMY. These effects were
      greater in the right than in the left side of these structures in rats with right
      turning preferences. WD reduced ethanol drinking but right turners drank
      significantly more than left turners on day 2 of testing and drank more on days 2
      and 3 than on day 1. No effects were observed on sucrose drinking. Similar groups
      were also trained to self-administer ethanol using a sucrose-fade sipper tube
      procedure that separated measures of ethanol seeking (bar pressing) and
      consumption. Following 14 days of vapor chamber exposure to ethanol, rats of all
      turning preferences had a lower rate of bar pressing on the first postwithdrawal
      day and shorter latencies to begin bar pressing on the third withdrawal day
      versus prewithdrawal baseline. Only right-turning-preference rats consumed more
      ethanol following withdrawal. CONCLUSIONS: These studies show that individual
      rats differ in postwithdrawal brain neurochemistry and ethanol consumption and
      that these differences are associated with differences in functional brain
      asymmetry.

PMID- 17010136
TI  - IgAs against acetaldehyde-modified red cell protein as a marker of ethanol
      consumption in male alcoholic subjects, moderate drinkers, and abstainers.
AB  - BACKGROUND: Alcohol abuse has been shown to result in the production of
      antibodies against acetaldehyde-modified epitopes in proteins. However, as yet,
      only limited information has been available on the clinical usefulness of such
      responses as markers of hazardous drinking. METHODS: We developed an ELISA to
      measure specific IgAs against acetaldehyde-protein adducts. This method was
      evaluated in cross-sectional and follow-up studies on male heavy drinkers with a
      current ethanol consumption of 40 to 540 g/d (n=40), moderate drinkers consuming
      1 to 40 g/d (n=25), and abstainers (n=16). The clinical assessments included
      detailed interviews on the amounts and patterns of ethanol consumption and
      various biochemical markers of alcohol abuse and liver function. RESULTS: The
      mean antiadduct IgAs (198+/-28 U/L) in the alcohol abusers were significantly
      higher than those in the moderate drinkers (58+/-11 U/L, p<0.001) or abstainers
      (28+/-8 U/L, p<0.001). The values of moderate drinkers were also higher than
      those in abstainers (p<0.05). The amount of ethanol consumed during the period of
      1 month preceding blood sampling correlated strongly with antiadduct IgAs
      (r=0.67, p<0.001). The sensitivity (73%) and specificity (94%) of this marker
      were found to exceed those of the conventional laboratory markers of alcohol
      abuse in comparisons contrasting heavy drinkers with abstainers although not in
      comparisons contrasting heavy drinkers with moderate drinkers. During abstinence,
      antiadduct IgAs disappeared with a mean rate of 3% per day. In additional
      analyses of possible marker combinations, antiadduct IgAs, together with CDT,
      were found to provide the highest sensitivity and specificity. CONCLUSIONS:
      Measurements of antiadduct IgAs may provide a new clinically useful marker of
      alcohol abuse, providing a close relationship between marker levels and the
      actual amounts of recent ethanol ingestion.

PMID- 17010137
TI  - Teenagers are right--parents do not know much: an analysis of adolescent-parent
      agreement on reports of adolescent substance use, abuse, and dependence.
AB  - BACKGROUND: Previous studies have shown that when assessing child
      psychopathology, parents tend to report more symptoms than children for
      externalizing disorders such as attention deficit hyperactivity disorder (ADHD),
      whereas children tend to report more symptoms for internalizing disorders such as
      major depression. Whether for clinical or research purposes, parents are also
      frequently asked to report on their children's experiences with alcohol and
      drugs. The purpose of this study was to analyze correspondence between adolescent
      and parent reports of adolescent substance use and abuse or dependence. METHODS:
      In the current study, 591 subjects 12 to 17 years old were interviewed using the
      child version of the Semi-Structured Assessment for the Genetics of Alcoholism (C
      SSAGA) as part of the Collaborative Study on the Genetics of Alcoholism (COGA).
      One parent was also interviewed about each adolescent using the parent version of
      the C-SSAGA. Sensitivities, specificities, and kappa coefficients were calculated
      to assess parental agreement with adolescent reports of lifetime substance use
      and Diagnostic and Statistical Manual of Mental Disorders-Third Revision
      substance abuse or dependence. RESULTS: The results indicate that parents are
      somewhat knowledgeable about their children's use of substances, particularly
      those that are used most commonly. For example, 55% of adolescents who had smoked
      cigarettes, 50% who had used alcohol, and 47% who had used marijuana had a parent
      who knew that they used. However, parents were less aware of substance-related
      problems experienced by their offspring, agreeing with adolescent reports only
      27% of the time for diagnoses of alcohol abuse or dependence and 26% of the time
      for diagnoses of marijuana abuse or dependence. Parent reports added few cases of
      substance use for 12- to 13 year-olds and essentially no cases for 16- to 17-year
      olds. Parent reports added a nominal number of diagnoses of substance abuse or
      dependence for older adolescents. CONCLUSIONS: Whether for clinical or research
      purposes, the results emphasize the importance of directly assessing adolescents
      regarding alcohol and other substance use disorders. Furthermore, investigators
      should consider the specific disorder(s) being investigated and the ages of the
      children being studied when determining whether to include parent reports as part
      of study design.

PMID- 17010138
TI  - Predictors of 16-year mortality among individuals initiating help-seeking for an
      alcoholic use disorder.
AB  - BACKGROUND AND METHODS: We examined rates and predictors of mortality in
      individuals (47% women) who had just initiated help-seeking for their alcohol use
      disorders (AUDs) at the start of the study (n=628) and were followed for 16
      years. RESULTS: For both women and men, the observed-to-expected mortality ratio
      (1.4) was lower than rates found in samples of treated individuals with AUDs,
      suggesting that those initiating help-seeking careers have better chances of long
      term survival. Of the individuals for whom cause of death was known, 68% died of
      alcohol-related causes. Men were more likely to die than were women. When gender
      was controlled, individuals who were older and unmarried and had more alcohol
      dependence symptoms at baseline were more likely to die over the 16-year period.
      When these baseline characteristics were controlled, better drinking outcomes at
      1 year were associated with a lower likelihood of subsequent death. The
      combination of a shorter duration of inpatient/residential care and better
      drinking outcomes at 1 year was related to a lower probability of death, as was
      the combination of a longer duration of outpatient care or Alcoholics Anonymous
      attendance and better drinking outcomes at 1 year. CONCLUSIONS: Efforts should be
      made to help providers identify individuals who are not responding positively to
      inpatient or residential treatment and intervene to motivate participation in
      continuing outpatient care and community 12-step self-help groups to reduce the
      likelihood of a chronic and fatal AUD course.

PMID- 17010139
TI  - Spouse abuse and alcohol problems among white, African American, and Hispanic
      U.S. Army soldiers.
AB  - BACKGROUND: Prior studies suggest racial/ethnic differences in the associations
      between alcohol misuse and spouse abuse. Some studies indicate that drinking
      patterns are a stronger predictor of spouse abuse for African Americans but not
      whites or Hispanics, while others report that drinking patterns are a stronger
      predictor for whites than African Americans or Hispanics. This study extends
      prior work by exploring associations between heavy drinking, alcohol-related
      problems, and risk for spouse abuse within racial/ethnic groups as well as
      variations associated with whether the perpetrator is drinking during the spouse
      abuse incident. METHODS: Cases (N=7,996) were all active-duty male, enlisted Army
      spouse abusers identified in the Army's Central Registry (ACR) who had also
      completed an Army Health Risk Appraisal (HRA) Survey between 1991 and 1998.
      Controls (N=17,821) were matched on gender, rank, and marital and HRA status.
      RESULTS: We found 3 different patterns of association between alcohol use and
      domestic violence depending upon both the race/ethnicity of the perpetrator and
      whether or not alcohol was involved in the spouse abuse event. First, after
      adjusting for demographic and psychosocial factors, weekly heavy drinking (>14
      drinks per week) and alcohol-related problems (yes to 2 or more of 6 alcohol
      related problem questions, including the CAGE) were significant predictors of
      domestic violence among whites and Hispanics only. Also for the white soldiers,
      the presence of family problems mediated the effect of alcohol-related problems
      on spouse abuse. Second, alcohol-related problems predicted drinking during a
      spouse abuse incident for all 3 race groups, but this relation was moderated by
      typical alcohol consumption patterns in Hispanics and whites only. Finally,
      alcohol-related problems predicted drinking during a spouse abuse incident, but
      this was a complex association moderated by different psychosocial or behavioral
      variables within each race/ethnic group. CONCLUSION: These findings suggest
      important cultural/social influences that interact with drinking patterns.

PMID- 17010140
TI  - The price of alcohol: a consideration of contextual factors.
AB  - BACKGROUND: The current study considers the determinants of prices charged for
      alcoholic beverages by on-premise and off-premise outlets in Alaska. Alcohol
      outlet densities, a surrogate measure for local retail competition, are expected
      to be negatively associated with prices while costs associated with distribution
      are expected to be positively related to prices. Community demographic and
      economic characteristics may affect observed local prices via the level of
      demand, retail costs borne by retailers, or the quality of brands offered for
      sale. METHODS: The core data for these analyses came from a telephone survey of
      Alaskan retail establishments licensed to serve alcohol. This survey utilized
      computer-assisted telephone interviewing (CATI) techniques to collect alcohol
      pricing information from on-premise (i.e., establishments where alcohol is
      consumed at the point of purchase such as bars and restaurants) and off-premise
      (i.e., establishments such as grocery stores and convenience markets where
      consumption occurs in other locations) alcohol retailers throughout the state of
      Alaska. Price estimates were developed for each beverage-type based on alcohol
      content. Separate regression analyses were used to model each of the 8 price
      indices (on-premise and off-premise measures for beer, spirits, wine, and the
      average price across beverage types). All regressions also controlled for a set
      of zip-code level indicators of community economic and demographic
      characteristics based on census data. RESULTS: Outlet density per roadway mile
      was unrelated to price for both on- and off-premise establishments, either across
      or between beverage types. In contrast, overall distribution costs did appear to
      be related to alcohol price. The demographic and economic variables, as a group,
      were significantly related to observed prices. CONCLUSIONS: More attention needs
      to be directed to the manner in which sellers and buyers behave relative to
      alcoholic beverages. Alcohol demand remains responsive to prices; yet, consumers
      have considerable latitude in determining the price that they pay for alcohol.

PMID- 17010141
TI  - Alcohol consumption, alcoholics anonymous membership, and homicide mortality
      rates in Ontario 1968 to 1991.
AB  - BACKGROUND: Research has shown a strong link between alcohol use and a variety of
      problems, including violence. Parker and colleagues have presented a selective
      disinhibition theory for the link between alcohol use and homicide (and other
      violence) that posits a causal relationship that is also influenced by other
      situational and contextual factors. This model is particularly well suited for
      aggregate-level investigations. In this study, we examine the impact of alcohol
      factors, including consumption measures and Alcoholics Anonymous (AA) membership
      rates, on homicide mortality rates in Ontario, and test predictions derived from
      the selective disinhibition model. METHODS: Time series analyses with ARIMA
      modeling were applied to total, male, and female homicide rates in Ontario
      between 1968 and 1991. The analyses performed included total alcohol consumption,
      spirits consumption, beer consumption, and wine consumption. Missing AA
      membership data were interpolated with cubic splines. RESULTS: For the total
      population and males, homicide rates were significantly and positively related to
      total alcohol consumption and to the consumption of beer and spirits. They were
      also negatively related to AA membership rates in the analyses involving spirits
      and wine and positively related to unemployment rates in the analyses involving
      beer, wine, and total alcohol. Among females, none of the measures were
      significant predictors of homicide mortality rates. CONCLUSIONS: These data
      provide important support for the selective disinhibition model and confirm
      important relationships between per capita consumption measures and homicide
      mortality rates, especially among males, seen in other studies. Additionally, the
      results for AA membership rates are consistent with the hypothesis that AA
      membership and treatment for misuse of alcohol can exert beneficial effects
      observable at the population level.

PMID- 17010142
TI  - Antioxidative treatment diminishes ethanol-induced congenital malformations in
      the rat.
AB  - BACKGROUND: Intrauterine exposure to ethanol causes embryonic and fetal growth
      retardation and maldevelopment. Oxidative stress in mother and offspring has been
      suggested to be part of the teratogenic mechanism, and supplementation of
      antioxidative agents to the pregnant women may therefore be of value in future
      prophylactic treatment regimen. There is a need for in vivo experimental work in
      this field, and in the present study, our aim was to investigate whether chronic
      ethanol consumption induced congenital malformations in rats and, if so, whether
      dietary supplementation of vitamin E (alpha-tocopherol) diminished such
      maldevelopment. METHODS: Female Sprague-Dawley rats were given drinking water
      containing 20% ethanol and half of these received food containing 5% vitamin E.
      Non-ethanol-exposed female rats, with or without vitamin E treatment, served as
      controls. The pregnancy was interrupted on gestational day 20 when the offspring
      was evaluated morphologically and fetal hepatic 8-iso-PGF(2alpha) levels were
      measured to assess the degree of fetal oxidative stress. RESULTS: Exposure to 20%
      ethanol increased maternal blood ethanol to 1.5 promille and increased resorption
      and malformation rates in the offspring. Maternal vitamin E treatment did not
      affect blood ethanol levels, but normalized fetal development. The fetal hepatic
      levels of 8-iso-PGF(2alpha) were increased in the ethanol-exposed group and
      normalized by vitamin E treatment of the mother. CONCLUSIONS: Ethanol exposure
      disturbs embryogenesis partly by enhanced oxidative stress, and the adverse
      effects can be ameliorated by antioxidative treatment.

PMID- 17010143
TI  - Role of beta-endorphin, corticotropin-releasing hormone, and autonomic nervous
      system in mediation of the effect of chronic ethanol on natural killer cell
      cytolytic activity.
AB  - BACKGROUND: We have recently shown that alcohol feeding suppresses natural killer
      (NK) cell cytolytic activity partly by decreasing the function of hypothalamic
      beta-endorphin (beta-EP) neurons. The neuronal mechanism by which hypothalamic
      beta-EP communicates with the spleen to regulate the action of ethanol on NK
      cells is not known. In the present study, we evaluated the roles of beta-EP
      neurons, corticotropin releasing hormone (CRH) neurons, and the autonomic nervous
      system (ANS) in regulation of the ethanol effect on splenic NK cell cytolytic
      function. METHODS: Male rats were fed an ethanol-containing liquid diet or
      control diets. These rats were used to determine the hormone release from the
      paraventricular nuclei (PVN) of the hypothalamus or used to determine the splenic
      NK cell cytolytic function after PVN administration of CRH or intraperitoneal
      (i.p.) administration of a ganglionic blocker chlorisondamine. The release of
      hormones from the PVN was measured using the push-pull perfusion method. Splenic
      cytolytic activity was determined using the 4-hour (51)Cr release assay against
      YAC-1 lymphoma target cells. RESULTS: Alcohol feeding decreased the amount of
      beta-EP but increased the amount of CRH in the push-pull perfusate (PPP) samples
      collected from the PVN. When exogenous beta-EP was perfused into the PVN, it
      suppressed the release of endogenous CRH found in PPP samples of the PVN.
      Conversely, perfusion of an opiate antagonist naltrexone into the PVN increased
      the levels of endogenous CRH in PPP samples of the PVN. In addition,
      administration of exogenous beta-EP in the PVN stimulated the cytolytic function
      of NK cells, an action that was antagonized by CRH as well as by ethanol.
      Corticotropin-releasing hormone and ethanol alone also had an inhibitory action
      on NK cells. Finally, the ganglionic blocker used prevented the effect that
      ethanol, beta-EP, and CRH had on NK cells. These data suggest that ethanol
      inhibits the function of NK cells partly by suppressing the influence of the beta
      EP-CRH-ANS signal to the spleen.

PMID- 17010144
TI  - Potential value of changes in cell markers in organotypic hippocampal cultures
      associated with chronic EtOH exposure and withdrawal: comparison with NMDA
      induced changes.
AB  - BACKGROUND: Previous studies have shown that withdrawal from ethanol (EtOH)
      exposure induces neuronal damage, as indicated by propidium iodide (PI) uptake,
      in organotypic hippocampal slice cultures. This is prevented by MK801, suggesting
      that damage is "excitotoxic," resulting from activation of N-methyl-d-aspartate
      (NMDA) receptors by endogenous glutamate. To avoid reliance on a single
      indicator, and to enable assessment of recovery from the EtOH withdrawal (EWD)
      insult, we assessed changes in cell markers for neurons and glia, as well as cell
      division, following either EWD or NMDA challenge (as a positive control).
      METHODS: Organotypic cultures from postnatal day (PND) 8 rats were cultured for 5
      days before exposure to EtOH (mean concentration approximately 65 mM) for 10 days
      before EWD. Cultures of the same "days in vitro" age (DIV16) were exposed to NMDA
      (200 microM) for 1 hour. Neuronal injury was visualized using PI and indices of
      neurons, glia, or cell division were measured at intervals up to 10 days
      following the neurotoxic insults. Each time point and measurement used separate
      slice cultures, and these were treated as separate experiments with paired
      controls. Regional neuronal content was assessed by neuronal nuclear protein
      (NeuN) and calbindin D28k (Calb), glial content by glial fibrillary acidic
      protein (GFAP), and cell division by bromodeoxyuridine (BrdU) incorporation, all
      measured immunohistochemically. RESULTS: Chronic exposure to EtOH was associated
      with a dramatic reduction in BrdU incorporation in all regions of cultures.
      Propidium iodide fluorescence in the CA1 region was elevated significantly after
      EWD and more so after NMDA challenge. Reduced immunoreactivity (IR) of NeuN and
      Calb suggested that loss of neurons resulted from the EWD insult.
      Bromodeoxyuridine incorporation was initially depressed even further by EWD, but
      had returned to control levels after 3 days. In contrast, following NMDA insult,
      BrdU incorporation was significantly and persistently elevated above control
      levels after 3 days. Glial fibrillary acidic protein was reduced immediately
      after both EWD and NMDA challenge. Several days after EWD, expression of neuronal
      and glial markers, although variable, had generally returned to control levels.
      In contrast, NeuN IR remained significantly reduced after NMDA challenge.
      CONCLUSIONS: In general, the use of additional markers supports data obtained
      with PI uptake alone and suggests that neurons (and glia) are lost from the
      culture following EWD or NMDA challenge. These cell markers recover several days
      after EWD, but it is unclear whether functional recovery accompanies these
      changes. If the dramatic effect of EtOH exposure and EWD on BrdU incorporation
      reflects reduced neuro- and gliogenesis, it is likely that this adversely affects
      long-term recovery from EWD. Finally, some markers showed significant and
      consistent changes after EWD, whereas others did not. This information may
      facilitate the use of this model in evaluation of potential medications that
      protect against and/or promote recovery from neurotoxicity.

PMID- 17010145
TI  - Chronic binge ethanol consumption accelerates progression of simian
      immunodeficiency virus disease.
AB  - BACKGROUND: While alcohol consumption is known to increase the incidence and
      severity of infections, the impact of alcohol consumption on human
      immunodeficiency virus (HIV) disease progression has been difficult to assess.
      Therefore, we examined the effect of ethanol on simian immunodeficiency virus
      (SIV) disease progression in a well-defined model utilizing rhesus macaques.
      METHODS: Alcohol was administered for 5 hours via an indwelling intragastric
      catheter to achieve an alcohol concentration of 50 to 60 mM for 4 consecutive
      days per week for the duration of the study. Control animals received isocaloric
      sucrose. After 3 months, animals were inoculated intravenously with 10,000 times
      the ID(50) of SIV(DeltaB670) and followed to end-stage disease. RESULTS: Plasma
      SIV ribonucleic acid (RNA) was higher in alcohol-consuming animals compared with
      sucrose-treated animals during the early asymptomatic stage of disease but not at
      later time points. This increase in viral set point was associated with more
      rapid progression to end-stage disease in macaques administered alcohol
      (median=374 days) compared with sucrose (median=900 days). The decline in blood
      CD4+ cells was similar in both groups of animals. CONCLUSIONS: This study
      indicates that frequent episodes of alcohol intoxication in SIV+ macaques
      increase viral set point in association with more rapid development of end-stage
      disease.

PMID- 17010146
TI  - Maternal oral intake mouse model for fetal alcohol spectrum disorders: ocular
      defects as a measure of effect.
AB  - BACKGROUND: This work was conducted in an effort to establish an oral intake
      model system in which the effects of ethanol insult that occur during early
      stages of embryogenesis can be easily examined and in which agents that may
      modulate ethanol's teratogenicity can be readily tested in vivo. The model system
      described utilizes the alcohol deprivation effect to obtain teratogenic levels of
      maternal ethanol intake on days 7 and 8 of pregnancy in C57Bl/6J mice. Ocular
      defects including microphthalmia and uveal coloboma, which have previously been
      shown to result from ethanol administered by gavage or via intraperitoneal
      injection on these days, served as the developmental end point for this study.
      The ocular defects are readily identifiable and their degree of severity is
      expected to correlate with concurrently developing defects of the central nervous
      system (CNS). METHODS: Female C57Bl/6J mice were maintained on an ethanol
      containing (4.8% v/v) liquid diet for 14 days and then mated during a subsequent
      abstinence period. Mice were then reexposed to ethanol on days 7 and 8 of
      pregnancy only. Control as well as ethanol-exposed dams were killed on their 14th
      day of pregnancy. Fetuses were then weighed, measured for crown rump length,
      photographed, and analyzed for ocular abnormalities. Globe size, palpebral
      fissure length, and pupil size and shape were noted for both the right and left
      eyes of all fetuses and informative comparisons were made. RESULTS: This exposure
      paradigm resulted in peak maternal blood alcohol concentrations that ranged from
      170 to 220 mg/dL on gestational day (GD) 8. Compared with the GD 14 fetuses from
      the normal control group, the pair-fed, acquisition controls, as well as the
      ethanol-exposed fetuses, were developmentally delayed and had reduced weights.
      Confirming previous studies, comparison of similarly staged control and treated
      GD 8 embryos illustrated reductions in the size of the forebrain in the latter.
      Subsequent ocular malformations were noted in 33% of the right eyes and 25% of
      the left eyes of the 103 GD 14 ethanol-exposed fetuses examined. This incidence
      of defects is twice that observed in the control groups. Additionally, it was
      found that the palpebral fissure length is directly correlated with globe size.
      CONCLUSIONS: The high incidence of readily identifiable ocular malformations
      produced by oral ethanol intake in this model and their relevance to human fetal
      alcohol spectrum disorders (FASD) makes this an excellent system for utilization
      in experiments involving factors administered to the embryo that might alter
      ethanol's teratogenic effects. Additionally, the fact that early ethanol insult
      yields ocular and forebrain abnormalities that are developmentally associated
      allows efficient specimen selection for subsequent detailed analyses of CNS
      effects in this in vivo mammalian FASD model.

PMID- 17010148
TI  - FcRgamma-chain signals in the absence of glycoprotein VI.

PMID- 17010149
TI  - The effect of levonorgestrel-releasing intrauterine system use on menstrual blood
      loss and the hemostatic, fibrinolytic/inhibitor systems in women with
      menorrhagia.
AB  - BACKGROUND: Menorrhagia is known to be associated with uterine fibroids,
      adenomyosis, pelvic infections, endometrial polyps and clotting defects. A viable
      alternative therapy to hysterectomy should alleviate heavy menstrual blood flow
      and consequently improve the quality-of-life measures in women presenting with
      menorrhagia. The levonorgestrel-releasing intrauterine system (LNG-IUS) ranks
      higher than medical treatments in terms of efficacy, comparable improvements in
      quality of life and psychological well-being. OBJECTIVE: The purpose of the study
      was to determine the effects of 6 months of LNG-IUS use on menstrual blood loss
      and the hemostatic, fibrinolytic/inhibitor systems in blood and the endometrium
      in women with menorrhagia with known pathologic causes. PATIENTS AND METHODS:
      Samples from 41 women were analyzed. Hemoglobin, hematocrit, thrombelastography,
      tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA),
      u-PA receptor (u-PAR), plasminogen activator inhibitor-1/2 (PAI-1/2), D-dimer and
      von Willebrand factor (VWF) were determined, and t-PA, u-PA and PAI-1/2 were also
      determined in endometrial tissue extracts. RESULTS: Menorrhagia was reduced in
      89% of women by 3 months; by 6 months all women had no menorrhagia, and 39% of
      women had become amenorrhoeic. Hemoglobin and hematocrit levels showed
      improvement, and reached normal reference levels by 6 months. There were no
      systemic changes in the fibrinolytic/inhibitor systems and VWF, except for a
      decreased u-PAR level. However, in the endometrium, significant elevations in PAI
      1/2 together with u-PAR levels were seen at 6 months. CONCLUSIONS: The slow
      levonorgestrel-release intrauterine device use results in high expression of
      fibrinolytic inhibitors (PAI-1/2) and upregulated u-PAR expression in the
      endometrium. Systemic hemostasis was not significantly altered. The study
      demonstrated that LNG-IUS is highly effective in the treatment of menorrhagia
      with known pathologic causes.

PMID- 17010147
TI  - Diffusion tensor imaging in children with fetal alcohol spectrum disorders.
AB  - BACKGROUND: Prenatal alcohol exposure, which is associated with macrostructural
      brain abnormalities, neurocognitive deficits, and behavioral disturbances, is
      characterized as fetal alcohol syndrome (FAS) in severe cases. The only published
      study thus far using diffusion tensor imaging (DTI) showed microstructural
      abnormalities in patients with FAS. The current study investigated whether
      similar abnormalities are present in less severely affected, prenatally exposed
      patients who did not display all of the typical FAS physical stigmata. METHODS:
      Subjects included 14 children, ages 10 to 13, with fetal alcohol spectrum
      disorders (FASD) and 13 matched controls. Cases with full-criteria FAS, mental
      retardation, or microcephaly were excluded. Subjects underwent MRI scans
      including DTI. RESULTS: Although cases with microcephaly were excluded, there was
      a trend toward smaller total cerebral volume in the FASD group (p=0.057, Cohen's
      d effect size =0.73). Subjects with FASD had greater mean diffusivity (MD) in the
      isthmus of the corpus callosum than controls (p=0.013, effect size =1.05),
      suggesting microstructural abnormalities in this region. There were no group
      differences in 5 other regions of the corpus callosum. Correlations between MD in
      the isthmus and facial dysmorphology were nonsignificant. CONCLUSIONS: These
      results suggest that even relatively mild forms of fetal alcohol exposure may be
      associated with microstructural abnormalities in the posterior corpus callosum
      that are detectable with DTI.

PMID- 17010150
TI  - Distribution and dynamic changes of sphingolipids in blood in response to
      platelet activation.
AB  - BACKGROUND: Sphingolipids are signaling molecules in a range of biological
      processes. While sphingosine-1-phosphate (S1P) is thought to be abundantly stored
      in platelets and released upon stimulation, knowledge about the distribution and
      function of other sphingolipids in blood is lacking. OBJECTIVES: To analyze the
      sphingolipid content of blood components with special emphasis on dynamic changes
      in platelets. METHODS: Blood components from mice and humans were prepared by
      gradient centrifugation and analyzed by liquid chromatography-mass spectrometry.
      Additionally, murine platelets were activated in vitro and in vivo. RESULTS:
      Isolated non-activated platelets of mice were devoid of S1P, but instead
      contained dihydrosphingosine-1-phosphate (dhS1P), along with a high concentration
      of ceramide. Activation of platelets in vitro led to a loss of dhS1P and an
      increase in sphingosine, accompanied by a reduction of ceramide content. Platelet
      activation in vivo led to an immediate and continuous rise of dhS1P in plasma,
      while S1P remained stable. The sphingolipid distribution of human blood was
      markedly different from mice. Human platelets contained dhS1P in addition to S1P.
      CONCLUSIONS: Mouse platelets contain dhS1P instead of S1P. Platelet activation
      causes loss of dhS1P and breakdown of ceramide, implying ceramidase activation.
      Release of dhS1P from activated platelets might be a novel signaling pathway.
      Finally, the sphingolipid composition of mouse and human blood shows large
      differences, which must be considered when studying sphingolipid biology.

PMID- 17010151
TI  - Value of D-dimer testing to decide duration of anticoagulation after deep vein
      thrombosis: not yet.

PMID- 17010152
TI  - Effect of pharmacologic plasminogen activator inhibitor-1 inhibition on cell
      motility and tumor angiogenesis.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is integrally involved in
      tumorigenesis by impacting on both proteolytic activity and cell migration during
      angiogenesis. OBJECTIVES: We hypothesized that an orally active small molecule
      inhibitor of PAI-1 (PAI-039; tiplaxtinin) could affect smooth muscle cell (SMC)
      attachment and migration in vitro on a vitronectin matrix, and exhibit
      antiangiogenic activity in vivo. METHODS: In vitro assays were used to assess the
      mechanism of inhibition of PAI-1 by PAI-039 using wild-type PAI-1 in the presence
      or absence of vitronectin and wild-type PAI-1 and specific PAI-1 mutants in SMC
      adhesion and migration assays. An in vivo tumor angiogenesis model was used to
      assess the effect of PAI-039 administration on neovascularization in a Matrigel
      implant. RESULTS: PAI-039 dose-dependently inhibited soluble, but not vitronectin
      bound, PAI-1. Cell adhesion assays using PAI-1 mutants unable to bind vitronectin
      (PAI-1K) or inactivate proteases (PAI-1R) further suggested that PAI-039
      inactivated PAI-1 by binding near its vitronectin domain. In a tumor angiogenesis
      model, PAI-039 treatment of wild-type mice dose-dependently decreased hemoglobin
      concentration and endothelial cell staining within the Matrigel implant,
      indicating reduced angiogenesis, but exhibited no in vivo efficacy in PAI-1 null
      mice. CONCLUSIONS: Administration of an orally active PAI-1 inhibitor prevented
      angiogenesis in a Matrigel implant. The lack of activity of PAI-039 against wild
      type PAI-1 bound to vitronectin and PAI-1K suggests PAI-039 binding near the
      vitronectin-binding site. Our studies further substantiate a role for PAI-1 in
      cellular motility and tumor angiogenesis, and suggest for the first time that
      these effects can be modulated pharmacologically.

PMID- 17010153
TI  - Association of the glutamate receptor subunit gene GRIN2B with attention
      deficit/hyperactivity disorder.
AB  - The glutamatergic signaling pathway represents an ideal candidate susceptibility
      system for attention-deficit/hyperactivity disorder (ADHD). Disruption of
      specific N-methyl-D-aspartate-type glutamate receptor subunit genes (GRIN1, 2A-D)
      in mice leads to significant alterations in cognitive and/or locomotor behavior
      including impairments in latent learning, spatial memory tasks and hyperactivity.
      Here, we tested for association of GRIN2B variants with ADHD, by genotyping nine
      single nucleotide polymorphisms (SNPs) in 205 nuclear families identified through
      probands with ADHD. Transmission of alleles from heterozygous parents to affected
      offspring was examined using the transmission/disequilibrium test. Quantitative
      trait analyses for the ADHD symptom dimensions [inattentive (IA) and
      hyperactive/impulsive (HI)] and cognitive measures of verbal working memory and
      verbal short-term memory were performed using the fbat program. Three SNPs showed
      significantly biased transmission (P < 0.05), with the strongest evidence of
      association found for rs2,284,411 (chi(2)= 7.903, 1 degree of freedom, P= 0.005).
      Quantitative trait analyses showed associations of these markers with both the IA
      and the HI symptom dimensions of ADHD but not with the cognitive measures of
      verbal short-term memory or verbal working memory. Our data suggest an
      association between variations in the GRIN2B subunit gene and ADHD as measured
      categorically or as a quantitatively distributed trait.

PMID- 17010154
TI  - Deficits in acetylcholine homeostasis, receptors and behaviors in choline
      transporter heterozygous mice.
AB  - Cholinergic neurons elaborate a hemicholinium-3 (HC-3) sensitive choline
      transporter (CHT) that mediates presynaptic, high-affinity choline uptake (HACU)
      in support of acetylcholine (ACh) synthesis and release. Homozygous deletion of
      CHT (-/-) is lethal shortly after birth (Ferguson et al. 2004), consistent with
      CHT as an essential component of cholinergic signaling, but precluding functional
      analyses of CHT contributions in adult animals. In contrast, CHT+/- mice are
      viable, fertile and display normal levels of synaptosomal HACU, yet demonstrate
      reduced CHT protein and increased sensitivity to HC-3, suggestive of underlying
      cholinergic hypofunction. We find that CHT+/- mice are equivalent to CHT+/+
      siblings on measures of motor co-ordination (rotarod), general activity (open
      field), anxiety (elevated plus maze, light/dark paradigms) and spatial learning
      and memory (Morris water maze). However, CHT+/- mice display impaired performance
      as a result of physical challenge in the treadmill paradigm, as well as reduced
      sensitivity to challenge with the muscarinic receptor antagonist scopolamine in
      the open field paradigm. These behavioral alterations are accompanied by
      significantly reduced brain ACh levels, elevated choline levels and brain region
      specific decreased expression of M1 and M2 muscarinic acetylcholine receptors.
      Our studies suggest that CHT hemizygosity results in adequate baseline ACh
      stores, sufficient to sustain many phenotypes, but normal sensitivities to
      physical and/or pharmacological challenge require full cholinergic signaling
      capacity.

PMID- 17010155
TI  - Chromosomal loci that influence oral nicotine consumption in C57BL/6J x C3H/HeJ
      F2 intercross mice.
AB  - Several studies have demonstrated that there are genetic influences on free
      choice oral nicotine consumption in mice. In order to establish the genetic
      architecture that underlies individual differences in free-choice nicotine
      consumption, quantitative trait loci (QTL) mapping was used to identify
      chromosomal regions that influence free-choice nicotine consumption in male and
      female F(2) mice derived from a cross between C57BL/6J and C3H/HeJ mice. These
      two mouse strains were chosen not only because they differ significantly for oral
      nicotine consumption, but also because they are at or near phenotypic extremes
      for all measures of nicotine sensitivity that have been reported. A four-bottle
      choice paradigm was used to assess nicotine consumption over an 8-day period. The
      four bottles contained water or water supplemented with 25, 50 or 100 microg/ml
      of nicotine base. Using micrograms of nicotine consumed per milliliter of total
      fluid consumed per day as the nicotine consumption phenotype, four significant
      QTL were identified. The QTL with the largest LOD score was located on distal
      chromosome 1 (peak LOD score = 15.7). Other chromosomes with significant QTL
      include central chromosome 4 (peak LOD score = 4.1), proximal chromosome 7 (peak
      LOD score = 6.1) and distal chromosome 15 (peak LOD score = 4.8). These four QTL
      appear to be responsible for up to 62% of the phenotypic variance in oral
      nicotine consumption.

PMID- 17010156
TI  - Cyclic-di-GMP-mediated signalling within the sigma network of Escherichia coli.
AB  - Bis-(3'-5')-cyclic-di-guanosine monophosphate (c-di-GMP) is a bacterial
      signalling molecule produced by diguanylate cyclases (DGC, carrying GGDEF
      domains) and degraded by specific phosphodiesterases (PDE, carrying EAL domains).
      Neither its full physiological impact nor its effector mechanisms are currently
      understood. Also, the existence of multiple GGDEF/EAL genes in the genomes of
      most species raises questions about output specificity and robustness of c-di-GMP
      signalling. Using microarray and gene fusion analyses, we demonstrate that at
      least five of the 29 GGDEF/EAL genes in Escherichia coli are not only stationary
      phase-induced under the control of the general stress response master regulator
      sigma(S) (RpoS), but also exhibit differential control by additional
      environmental and temporal signals. Two of the corresponding proteins, YdaM
      (GGDEF only) and YciR (GGDEF + EAL), which in vitro show DGC and PDE activity,
      respectively, play an antagonistic role in the expression of the biofilm
      associated curli fimbriae. This control occurs at the level of transcription of
      the curli and cellulose regulator CsgD. Moreover, we show that H-NS positively
      affects curli expression by inversely controlling the expression of ydaM and
      yciR. Furthermore, we demonstrate a temporally fine-tuned GGDEF cascade in which
      YdaM controls the expression of another GGDEF protein, YaiC. By genome-wide
      microarray analysis, evidence is provided that YdaM and YciR strongly and nearly
      exclusively control CsgD-regulated genes. We conclude that specific GGDEF/EAL
      proteins have very distinct expression patterns, and when present in
      physiological amounts, can act in a highly precise, non-global and perhaps
      microcompartmented manner on a few or even a single specific target(s).

PMID- 17010157
TI  - Competition of bacteriophage polypeptides with native replicase proteins for
      binding to the DNA sliding clamp reveals a novel mechanism for DNA replication
      arrest in Staphylococcus aureus.
AB  - Bacteriophages have evolved specific mechanisms that redirect bacterial metabolic
      pathways to the bacteriophage reproduction cycle. In this study, we characterized
      the bactericidal mechanism of two polypeptides from bacteriophages Twort and G1
      that target the DNA sliding clamp of Staphylococcus aureus. The DNA sliding
      clamp, which tethers DNA polymerase to its template and thereby confers
      processivity upon the enzyme, was found to be essential for the viability of S.
      aureus. Expression of polypeptides TwortORF168 and G1ORF240 in S. aureus
      selectively inhibited DNA replication which in turn resulted in cell death. Both
      polypeptides specifically inhibited the S. aureus DNA replicase that was
      reconstituted in vitro but not the corresponding replicase of Streptococcus
      pyogenes. We demonstrated that inhibition of DNA synthesis is multifaceted and
      occurs via binding the DNA sliding clamp: TwortORF168 and G1ORF240 bound tightly
      to the DNA sliding clamp and prevented both its loading onto DNA and its
      interaction with DNA polymerase C. These results elucidate the impact of
      bacteriophage polypeptide expression upon DNA replication in the growing cell.

PMID- 17010158
TI  - Biochemical and genetic characterization of an early step in a novel pathway for
      the biosynthesis of aromatic amino acids and p-aminobenzoic acid in the archaeon
      Methanococcus maripaludis.
AB  - Methanococcus maripaludis is a strictly anaerobic, methane-producing archaeon and
      facultative autotroph capable of biosynthesizing all the amino acids and vitamins
      required for growth. In this work, the novel 6-deoxy-5-ketofructose-1-phosphate
      (DKFP) pathway for the biosynthesis of aromatic amino acids (AroAAs) and p
      aminobenzoic acid (PABA) was demonstrated in M. maripaludis. Moreover, PABA was
      shown to be derived from an early intermediate in AroAA biosynthesis and not from
      chorismate. Following metabolic labelling with [U-(13)C]-acetate, the expected
      enrichments for phenylalanine and arylamine derived from PABA were observed. DKFP
      pathway activity was reduced following growth with aryl acids, an alternative
      source of the AroAAs. Lastly, a deletion mutant of aroA', which encodes the first
      step in the DKFP pathway, required AroAAs and PABA for growth. Complementation of
      the mutants by an aroA' expression vector restored the wild-type phenotype. In
      contrast, a deletion of aroB', which encodes the second step in the DKFP pathway,
      did not require AroAAs or PABA for growth. Presumably, methanococci contain an
      alternative activity for this step. These results identify the initial reactions
      of a new pathway for the biosynthesis of PABA in methanococci.

PMID- 17010159
TI  - Virulence of Agrobacterium tumefaciens requires phosphatidylcholine in the
      bacterial membrane.
AB  - Phosphatidylcholine (PC, lecithin) has long been considered a solely eukaryotic
      membrane lipid. Only a minority of all bacteria is able to synthesize PC. The
      plant-transforming bacterium Agrobacterium tumefaciens encodes two potential PC
      forming enzymes, a phospholipid N-methyltransferase (PmtA) and a PC synthase
      (Pcs). We show that PC biosynthesis and tumour formation on Kalanchoe plants was
      impaired in the double mutant. The virulence defect was due to a complete lack of
      the type IV secretion machinery in the Agrobacterium PC mutant. Our results
      strongly suggest that PC in bacterial membranes is an important determinant for
      the establishment of host-microbe interactions.

PMID- 17010161
TI  - Serotonin 5-HT(2A) receptor activation induces 2-arachidonoylglycerol release
      through a phospholipase c-dependent mechanism.
AB  - To date, several studies have demonstrated that phospholipase C-coupled receptors
      stimulate the production of endocannabinoids, particularly 2
      arachidonoylglycerol. There is now evidence that endocannabinoids are involved in
      phospholipase C-coupled serotonin 5-HT(2A) receptor-mediated behavioral effects
      in both rats and mice. The main objective of this study was to determine whether
      activation of the 5-HT(2A) receptor leads to the production and release of the
      endocannabinoid 2-arachidonoylglycerol. NIH3T3 cells stably expressing the rat 5
      HT(2A) receptor were first incubated with [(3)H]-arachidonic acid for 24 h.
      Following stimulation with 10 mum serotonin, lipids were extracted from the assay
      medium, separated by thin layer chromatography, and analyzed by liquid
      scintillation counting. Our results indicate that 5-HT(2A) receptor activation
      stimulates the formation and release of 2-arachidonoylglycerol. The 5-HT(2A)
      receptor-dependent release of 2-arachidonoylglycerol was partially dependent on
      phosphatidylinositol-specific phospholipase C activation. Diacylglycerol produced
      downstream of 5-HT(2A) receptor-mediated phospholipase D or phosphatidylcholine
      specific phospholipase C activation did not appear to contribute to 2
      arachidonoylglycerol formation in NIH3T3-5HT(2A) cells. In conclusion, our
      results support a functional model where neuromodulatory neurotransmitters such
      as serotonin may act as regulators of endocannabinoid tone at excitatory synapses
      through the activation of phospholipase C-coupled G-protein coupled receptors.

PMID- 17010162
TI  - Genome characterization, analysis of virulence and transformation of
      Microbacterium nematophilum, a coryneform pathogen of the nematode Caenorhabditis
      elegans.
AB  - A coryneform bacterium designated Microbacterium nematophilum has previously been
      reported to act as a pathogen for Caenorhabditis elegans. This bacterium is able
      to colonize the rectum of infected worms and cause localized swelling,
      constipation and slowed growth. Additional isolates and analysis of this
      bacterium are described here. Tests of pathogenicity on other Caenorhabditis
      nematodes show that M. nematophilum infection is lethal to most species in the
      genus, in contrast to its relatively mild effects on C. elegans. The size and
      geometry of the pathogen genome have been determined as a closed circular
      molecule of 2.85 Mb with high G+C content. Bacteria also harbor a 55 kb plasmid,
      pMN1, which is largely composed of a lysogenic bacteriophage genome. Mutagenesis
      experiments have yielded stable avirulent mutants of M. nematophilum. As a first
      step towards molecular genetic analysis, methods for low-efficiency
      transformation of M. nematophilum have been developed.

PMID- 17010160
TI  - The Rcs phosphorelay system is specific to enteric pathogens/commensals and
      activates ydeI, a gene important for persistent Salmonella infection of mice.
AB  - Bacteria utilize phosphorelay systems to respond to environmental or
      intracellular stimuli. Salmonella enterica encodes a four-step phosphorelay
      system that involves two sensor kinase proteins, RcsC and RcsD, and a response
      regulator, RcsB. The physiological stimulus for Rcs phosphorelay activation is
      unknown; however, Rcs-regulated genes can be induced in vitro by osmotic shock,
      low temperature and antimicrobial peptide exposure. In this report we investigate
      the role of the Rcs pathway using phylogenetic analysis and experimental
      techniques. Phylogenetic analysis determined that full-length RcsC- and RcsD-like
      proteins are generally restricted to Enterobacteriaceae species that have an
      enteric pathogenic or commensal relationship with the host. Experimental data
      show that RcsD and RcsB, in addition to RcsC, are important for systemic
      infection in mice and polymyxin B resistance in vitro. To identify Rcs-regulated
      genes that confer these phenotypes, we took advantage of our observation that
      RcsA, a transcription factor and binding partner of RcsB, is not required for
      polymyxin B resistance or survival in mice. S. enterica serovar Typhimurium
      oligonucleotide microarrays were used to identify 18 loci that are activated by
      RcsC, RcsD and RcsB but not RcsA. Five of the 18 loci encode genes that
      contribute to polymyxin B resistance. One of these genes, ydeI, was shown by
      quantitative real-time PCR to be regulated by the Rcs pathway independently of
      RcsA. Additionally, the stationary-phase sigma factor, RpoS (sigmaS), regulates
      ydeI transcription. In vivo infections show that ydeI mutants are out-competed by
      wild type 10- to 100-fold after oral inoculation, but are only modestly
      attenuated after intraperitoneal inoculation. These data indicate that ydeI is an
      Rcs-activated gene that plays an important role in persistent infection of mice,
      possibly by increasing bacterial resistance to antimicrobial peptides.

PMID- 17010163
TI  - Effect of sulfur-containing compounds on Bacillus cellulosome-associated 'CMCase'
      and 'Avicelase' activities.
AB  - The isolation of cellulosomes from clostridial sources has been extensively
      studied; however, the isolation of cellulosomes from facultative soil anaerobes
      of the family Bacillaceae is not as well characterized. The Bacillus cellulosome
      (celluloxylanosome) essentially consists of two complex components: C-I and C-II.
      This multi-component complex enables Bacillus to degrade a variety of
      carbonaceous compounds as it is composed of several enzymes, such as cellulases,
      xylanases and other degradative enzymes. The cellulosomal cellulases from
      Bacillus megaterium were purified using cellulose affinity chromatography,
      followed by Sepharose 4B gel filtration chromatography. The objective of this
      investigation was to establish the effect of sulfate and sulfide on cellulosomal
      'cellulase' activity. An increase in sulfide concentration led to a general
      enhancement of cellulosomal-associated cellulolytic activity, whereas an increase
      in sulfate concentration resulted in an inhibition of the cellulosome-associated
      cellulolytic activity.

PMID- 17010164
TI  - Monomeric solution structure of the helicase-binding domain of Escherichia coli
      DnaG primase.
AB  - DnaG is the primase that lays down RNA primers on single-stranded DNA during
      bacterial DNA replication. The solution structure of the DnaB-helicase-binding C
      terminal domain of Escherichia coli DnaG was determined by NMR spectroscopy at
      near-neutral pH. The structure is a rare fold that, besides occurring in DnaG C
      terminal domains, has been described only for the N-terminal domain of DnaB. The
      C-terminal helix hairpin present in the DnaG C-terminal domain, however, is
      either less stable or absent in DnaB, as evidenced by high mobility of the C
      terminal 35 residues in a construct comprising residues 1-171. The present
      structure identifies the previous crystal structure of the E. coli DnaG C
      terminal domain as a domain-swapped dimer. It is also significantly different
      from the NMR structure reported for the corresponding domain of DnaG from the
      thermophile Bacillus stearothermophilus. NMR experiments showed that the DnaG C
      terminal domain does not bind to residues 1-171 of the E. coli DnaB helicase with
      significant affinity.

PMID- 17010165
TI  - Interaction of HIV-1 with dendritic cell-specific intercellular adhesion molecule
      3-grabbing nonintegrin-expressing cells is influenced by gp120 envelope
      modifications associated with disease progression.
AB  - Dendritic cells can enhance the replication of HIV-1 in CD4(+) lymphocytes
      through the interaction of the gp120 envelope protein with such molecules as
      dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin.
      The variable loops of gp120 have previously been shown to modulate the
      interaction of HIV-1 with its principal receptor CD4 and its various coreceptors,
      namely CCR5 and CXCR4. Here, we utilized a panel of molecular cloned viruses to
      identify whether gp120 modifications can influence the virus interaction with
      immature dendritic cells or a cell line expressing dendritic cell-specific
      intercellular adhesion molecule-3-grabbing nonintegrin (Raji-DC-SIGN). The
      viruses encompass the R5, R5X4 and X4 phenotypes, and are based upon V1V2 and V3
      sequences from a patient with disease progression. We found that dendritic cell
      specific intercellular adhesion molecule-3-grabbing nonintegrin enhancement of
      virus replication can be modulated by the V1V2 length, the overall V3 charge and
      N-linked glycosylation patterns; similar results were observed with immature
      dendritic cells. Viruses with higher V3 charges are more readily transferred to
      CD4(+) lymphocytes when the V1V2 region is longer and contains an additional N
      linked glycosylation site, whereas transfer of viruses with lower V3 charges is
      greater when the V1V2 region is shorter. Viruses differing in the V1V2 and V3
      regions also demonstrated differential capture by Raji-DC-SIGN cells in the
      presence of mannan. These results indicate that the interaction between HIV-1 and
      immature dendritic cells via such molecules as dendritic cell-specific
      intercellular adhesion molecule-3-grabbing nonintegrin may have a role in
      selecting viruses undergoing transmission and evolution during disease
      progression.

PMID- 17010166
TI  - A role for serglycin proteoglycan in granular retention and processing of mast
      cell secretory granule components.
AB  - In the absence of serglycin proteoglycans, connective tissue-type mast cells fail
      to assemble mature metachromatic secretory granules, and this is accompanied by a
      markedly reduced ability to store neutral proteases. However, the mechanisms
      behind these phenomena are not known. In this study, we addressed these issues by
      studying the functionality and morphology of secretory granules as well as the
      fate of the secretory granule proteases in bone marrow-derived mast cells from
      serglycin(+/+) and serglycin(-/-) mice. We show that functional secretory
      vesicles are formed in both the presence and absence of serglycin, but that dense
      core formation is defective in serglycin(-/-) mast cell granules. The low levels
      of mast cell proteases present in serglycin(-/-) cells had a granular location,
      as judged by immunohistochemistry, and were released following exposure to
      calcium ionophore, indicating that they were correctly targeted into secretory
      granules even in the absence of serglycin. In the absence of serglycin, the fates
      of the serglycin-dependent proteases differed, including preferential
      degradation, exocytosis or defective intracellular processing. In contrast, beta
      hexosaminidase storage and release was not dependent on serglycin. Together,
      these findings indicate that the reduced amounts of neutral proteases in the
      absence of serglycin is not caused by missorting into the constitutive pathway of
      secretion, but rather that serglycin may be involved in the retention of the
      proteases after their entry into secretory vesicles.

PMID- 17010167
TI  - Crystal structure and enzymatic properties of a bacterial family 19 chitinase
      reveal differences from plant enzymes.
AB  - We describe the cloning, overexpression, purification, characterization and
      crystal structure of chitinase G, a single-domain family 19 chitinase from the
      Gram-positive bacterium Streptomyces coelicolor A3(2). Although chitinase G was
      not capable of releasing 4-methylumbelliferyl from artificial
      chitooligosaccharide substrates, it was capable of degrading longer
      chitooligosaccharides at rates similar to those observed for other chitinases.
      The enzyme was also capable of degrading a colored colloidal chitin substrate
      (carboxymethyl-chitin-remazol-brilliant violet) and a small, presumably
      amorphous, subfraction of alpha-chitin and beta-chitin, but was not capable of
      degrading crystalline chitin completely. The crystal structures of chitinase G
      and a related Streptomyces chitinase, chitinase C [Kezuka Y, Ohishi M, Itoh Y,
      Watanabe J, Mitsutomi M, Watanabe T & Nonaka T (2006) J Mol Biol358, 472-484],
      showed that these bacterial family 19 chitinases lack several loops that extend
      the substrate-binding grooves in family 19 chitinases from plants. In accordance
      with these structural features, detailed analysis of the degradation of
      chitooligosaccharides by chitinase G showed that the enzyme has only four
      subsites (- 2 to + 2), as opposed to six (- 3 to + 3) for plant enzymes. The most
      prominent structural difference leading to reduced size of the substrate-binding
      groove is the deletion of a 13-residue loop between the two putatively catalytic
      glutamates. The importance of these two residues for catalysis was confirmed by a
      site-directed mutagenesis study.

PMID- 17010168
TI  - Reduction of a biochemical model with preservation of its basic dynamic
      properties.
AB  - The complexity of full-scale metabolic models is a major obstacle for their
      effective use in computational systems biology. The aim of model reduction is to
      circumvent this problem by eliminating parts of a model that are unimportant for
      the properties of interest. The choice of reduction method is influenced both by
      the type of model complexity and by the objective of the reduction; therefore, no
      single method is superior in all cases. In this study we present a comparative
      study of two different methods applied to a 20D model of yeast glycolytic
      oscillations. Our objective is to obtain biochemically meaningful reduced models,
      which reproduce the dynamic properties of the 20D model. The first method uses
      lumping and subsequent constrained parameter optimization. The second method is a
      novel approach that eliminates variables not essential for the dynamics. The
      applications of the two methods result in models of eight (lumping), six
      (elimination) and three (lumping followed by elimination) dimensions. All models
      have similar dynamic properties and pin-point the same interactions as being
      crucial for generation of the oscillations. The advantage of the novel method is
      that it is algorithmic, and does not require input in the form of biochemical
      knowledge. The lumping approach, however, is better at preserving biochemical
      properties, as we show through extensive analyses of the models.

PMID- 17010169
TI  - Human parvovirus B19 erythrovirus. Methods established for virological and
      diagnostic aspects.

PMID- 17010172
TI  - Systemic antibiotic therapy of acne vulgaris.
AB  - BACKGROUND: Inflammatory, medium to severe acne vulgaris is treated with systemic
      antibiotics worldwide. The rationale is an effect on Propionibacterium acnes as
      well as the intrinsic anti-inflammatory properties of these antibiotics. Although
      there are no correlations between the number of P. acnes and the severity of the
      disease, associations between the degree of humoral and cellular immune responses
      towards P. acnes and the severity of acne have been reported. Exact data on
      practical use of these compounds, such as differential efficacy or side effects
      are unavailable. A summary of currently available studies is presented. METHODS:
      The data of studies of systemic antibiotic therapy of acne vulgaris up to 1975,
      the summary of literature in English up to 1999, a systematic review of
      minocycline from 2002 as well as the data of randomized controlled studies
      published and listed in Medline thereafter were reviewed. RESULTS: Tetracyclines
      [tetracycline 1,000 mg daily, doxycycline 100 (-200) mg daily, minocycline 100 (
      200) mg daily, lymecycline 300 (-600) mg] and erythromycin 1 000 mg daily are
      significantly more effective than placebo in the systemic treatment of
      inflammatory acne. The data for tetracycline are best founded. Clindamycin is
      similarly effective. Co-trimoxazole and trimethoprim are likely to be effective.
      Clear differences between the tetracyclines or between tetracycline and
      erythromycin cannot be ascertained. The data for the combination with topical
      treatments [topical benzoyl peroxide (BPO) or retinoids] suggest synergistic
      effects. Therefore systemic antibiotics should not be used as monotherapy. In
      case of similar efficacy, other criteria, such as pharmacokinetics (doxycycline,
      minocycline, lymecycline have longer half-lives than tetracyclines), the rate of
      side-effects (tetracycline: side effect-rate approximately 4 % mild side effects;
      erythromycin: frequent gastrointestinal complaints; minocycline: rare, but
      potentially severe hypersensitivity reactions; doxycycline: dose-dependent
      phototoxic reactions), the resistance rate [percentage of resistant bacteria
      higher with erythromycin (approximately 50 %) than with tetracycline-therapy
      (approximately 20 %)], and the costs of therapy have to be taken into account.
      CONCLUSIONS: The systemic antibiotic therapy of widespread papulo-pustular acne
      not amenable to a topical therapy is effective and well-tolerated. In general
      therapy can be carried out for 3 months and should be combined with BPO to
      prevent resistance.

PMID- 17010173
TI  - HLA markers in familial Lichen sclerosus.
AB  - BACKGROUND: Lichen sclerosus (LS) has been identified with increased frequency in
      families,often associated with HLA markers, mainly DQ7. A genetic co-etiology
      seems likely in this setting. Moreover, there is an association of LS with
      autoimmune disorders, such as the presence of anti-thyroid peroxidase
      autoantibodies (anti-TPO), a hallmark of autoimmune thyroid diseases. PATIENTS
      AND METHODS: In 3 families affected by LS, we verified their HLA markers, and
      identified previously undiagnosed cases of LS and autoimmune disorders. 30
      individuals were examined with history, skin biopsy, HLA class I and II typing by
      PCR-SSP, and measurement of anti-TPO, free thyroxine and thyroidstimulating
      hormones (TSH) levels. RESULTS: There were 8 cases of LS, 50 % of them anti-TPO+.
      Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected.
      Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07,
      DRB4*. The three latter have been previously associated with LS. CONCLUSION: New
      cases of LS and autoimmune disorders can be detected in first degree relatives of
      patients with LS. The presence of anti-TPO antibodies strongly suggests
      autoimmune thyroiditis. There is intra-familial association between the haplotype
      HLA-B*15 -DRB1*04 -DRB4* and anti-TPO,emphasizing their link with thyroiditis.
      New familial approaches might help to make clear the pathogenesis of LS and its
      association with autoimmune diseases.

PMID- 17010174
TI  - Three-dimensional documentation of wound healing: first results of a new
      objective method for measurement.
AB  - BACKGROUND: The objective assessment of wound healing is one essential parameter
      of quality assurance in a modern chronic wound management program. In the past
      assessment has been based exclusively on a two-dimensional measurement of the
      wound surface with planimetry or digital photo documentation in combination with
      such measurements. An objective method for measuring the volume of chronic wounds
      has not yet been available. PATIENTS AND METHODS: In cooperation with the company
      RSI, we linked digital photography, optical raster by means of digital scanner,
      and picture processing software (DigiSkin) for an exact three-dimensional image
      of chronic wounds. The generated point clouds allow the visual, computer-assisted
      three-dimensional quantification and can document the course of healing of
      chronic wounds. RESULTS: In comparison to currently available systems, our new
      method makes possible the objective measurement of volume changes and wound
      healing course in chronic wounds.We demonstrate the utility of the system in
      reference to three patients with chronic venous leg ulcers. CONCLUSIONS: Using
      this new, objective three-dimensional wound measurement system,it is possible to
      reliably quantify changes in wound healing for the first time. Future clinical
      studies have a new option for the gathering of data which will facilitate
      evidenced-based conclusions.

PMID- 17010175
TI  - Follicular rash during therapy with erlotinib (Tarceva).
AB  - Erlotinib is a small-molecule tyrosine kinase inhibitor of the EGF receptor which
      has become an important oncological agent, used primarily in treating non-small
      cell lung cancer. The most common side effects of this class of EGF receptor
      antagonists are cutaneous rashes. The severity of the skin rash seems to be
      correlated to clinical response and should be a motivating factor to continue
      therapy. We report a case of a patient who developed a follicular rash during
      therapy with erlotinib.

PMID- 17010176
TI  - Axillary acne agminata (lupus miliaris disseminatus faciei with axillary
      involvement).
AB  - Acne agminata (AA) and lupus miliaris disseminatus faciei (LMDF) have been used
      to describe very similar clinical conditions and it is now generally accepted
      that they are synonymous. The cause of these disorders has not been determined.
      Clinically the disease presents with often agminated redbrown to yellow papules
      which occasionally become pustular. Microscopically, superficial granulomatous
      inflammation with perifollicular caseating granulomas is the hallmark. Axillary
      involvement with LMDF has rarely been reported; in this area AA has been the
      preferred term. When only the axillae are affected, it may be difficult to
      distinguish acne agminata from other granulomatous diseases, especially from
      granulomas caused by antiperspirants containing aluminumzirconium complexes. We
      describe a 36-year-old woman with axillary acne agminata.

PMID- 17010177
TI  - [Cellulite--the greatest skin problem in healthy people? An approach].
AB  - Cellulite or so called orange peel skin affects 80-90 % of all females. It is not
      considered as a pathological condition but as aesthetically disturbing dimpling
      of the skin seen most commonly on the thighs and buttocks. Despite its high
      prevalence, there have been only a few scientific investigations into the
      pathophysiology of cellulite reflected in the medical literature. A lack of
      knowledge regarding specific aetiopathogenetic factors and pathogenesis at large
      currently limits treatment options. The preferred hypotheses about the origin of
      cellulite include: gender specific dimorphic skin architecture, altered
      connective tissue septae, vascular changes and inflammatory processes. The most
      widely discussed management options include: attenuation of aggravating factors,
      physical procedures including laser therapy and application of topical
      incorporating actives. The latter approach has been evidence-based with respect
      to caffeine liposomal cream and retinol cream.

PMID- 17010178
TI  - Zoster-associated neuralgias.

PMID- 17010179
TI  - [Painless ulcers of the forefoot and acroosteolyses].

PMID- 17010180
TI  - [Orientation guides for excision lines and flap design].

PMID- 17010181
TI  - Interdisciplinary guidelines of the German Society of Coloproctology and the
      German Society of Dermatology. Anal skin tags.

PMID- 17010182
TI  - German dermatologists and their contributions to Turkish dermatology.

PMID- 17010184
TI  - [Working group of Dermato-Oncology ADO].

PMID- 17010185
TI  - Cost-utility of routine cataract surgery.
AB  - BACKGROUND: If decisions on health care spending are to be as rational and
      objective as possible, knowledge on cost-effectiveness of routine care is
      essential. Our aim, therefore, was to evaluate the cost-utility of routine
      cataract surgery in a real-world setting. METHODS: Prospective assessment of
      health-related quality of life (HRQoL) of patients undergoing cataract surgery.
      219 patients (mean (SD) age 71 (11) years) entering cataract surgery (in 87 only
      first eye operated, in 73 both eyes operated, in 59 first eye had been operated
      earlier) filled in the 15D HRQoL questionnaire before and six months after
      operation. Direct hospital costs were obtained from a clinical patient
      administration database and cost-utility analysis performed from the perspective
      of the secondary care provider extrapolating benefits of surgery to the remaining
      statistical life-expectancy of the patients. RESULTS: Mean (SD) utility score (on
      a 0-1 scale) increased statistically insignificantly from 0.82 (0.13) to 0.83
      (0.14). Of the 15 dimensions of the HRQoL instrument, only seeing improved
      significantly after operation. Mean utility score improved statistically
      significantly only in patients reporting significant or major preoperative seeing
      problems. Of the subgroups, only those whose both eyes were operated during
      follow-up showed a statistically significant (p < 0.001) improvement. Cost per
      quality-adjusted life year (QALY) gained was euro5128 for patients whose both
      eyes were operated and euro8212 for patients with only one eye operated during
      the 6-month follow-up. In patients whose first eye had been operated earlier mean
      HRQoL deteriorated after surgery precluding the establishment of the cost per
      QALY. CONCLUSION: Mean utility gain after routine cataract surgery in a real
      world setting was relatively small and confined mostly to patients whose both
      eyes were operated. The cost of cataract surgery per quality-adjusted life year
      gained was much higher than previously reported and associated with considerable
      uncertainty.

PMID- 17010186
TI  - Functional expression of a single-chain antibody to ErbB-2 in plants and cell
      free systems.
AB  - BACKGROUND: Aberrant signaling by ErbB-2 (HER 2, Neu), a member of the human
      Epidermal Growth Factor (EGF) receptor family, is associated with an aggressive
      clinical behaviour of carcinomas, particularly breast tumors. Antibodies
      targeting the ErbB-2 pathway are a preferred therapeutic option for patients with
      advanced breast cancer, but a worldwide deficit in the manufacturing capacities
      of mammalian cell bioreactors is foreseen. METHODS: Herein, we describe a multi
      platform approach for the production of recombinant Single chain Fragments of
      antibody variable regions (ScFvs) to ErbB-2 that involves their functional
      expression in (a) bacteria, (b) transient as well as stable transgenic tobacco
      plants, and (c) a newly developed cell-free transcription-translation system.
      RESULTS: An ScFv (ScFv800E6) was selected by cloning immunoglobulin sequences
      from murine hybridomas, and was expressed and fully functional in all the
      expression platforms, thereby representing the first ScFv to ErbB-2 produced in
      hosts other than bacteria and yeast. ScFv800E6 was optimized with respect to
      redox synthesis conditions. Different tags were introduced flanking the ScFv800E6
      backbone, with and without spacer arms, including a novel Strep II tag that
      outperforms conventional streptavidin-based detection systems. ScFv800E6 was
      resistant to standard chemical radiolabeling procedures (i.e. Chloramine T),
      displayed a binding ability extremely similar to that of the parental monovalent
      Fab' fragment, as well as a flow cytometry performance and an equilibrium binding
      affinity (Ka approximately 2 x 10(8) M(-1)) only slightly lower than those of the
      parental bivalent antibody, suggesting that its binding site is conserved as
      compared to that of the parental antibody molecule. ScFv800E6 was found to be
      compatible with routine reagents for immunohistochemical staining. CONCLUSION:
      ScFv800E6 is a useful reagent for in vitro biochemical and immunodiagnostic
      applications in oncology, and a candidate for future in vivo studies.

PMID- 17010187
TI  - Aortic obstruction: anatomy and echocardiography.
AB  - Echocardiography is a valuable non-invasive technique for identifying the site
      and type of aortic obstruction. Knowledge of the morphological details of each
      type of obstruction is the basis for correct interpretation of the diagnostic
      images and clinical decisions. This study was undertaken to correlate the
      echocardiographic images with anatomic specimens of equivalent valvular and
      supravalvular aortic obstruction. Specimens were part of the collection of the
      Department of Embryology. Fifty six patients were studied, and forty specimens
      with aortic obstruction were analyzed. Echocardiographic characteristics: Thirty
      one (55.3%) patients were women and twenty five (44.7%) men. Valvular aortic
      obstruction was found in Thirty six patients (64.3 %) and supravalvular aortic
      obstruction in twenty (35.7%). Anatomic characteristics: Of the forty specimens
      examined, twenty one (52.5%) had valvular aortic obstruction and nineteen (47.5%)
      supravalvular aortic obstruction. The anatomoechocardiographic correlation
      clearly showed that the anatomic findings of the specimen hearts and aortas
      corresponded to echocardiographic images of valvular and supravalvular aortic
      obstruction and provided solid corroboration of echocardiographic diagnoses.

PMID- 17010188
TI  - Computational reconstruction of transcriptional regulatory modules of the yeast
      cell cycle.
AB  - BACKGROUND: A transcriptional regulatory module (TRM) is a set of genes that is
      regulated by a common set of transcription factors (TFs). By organizing the
      genome into TRMs, a living cell can coordinate the activities of many genes and
      carry out complex functions. Therefore, identifying TRMs is helpful for
      understanding gene regulation. RESULTS: Integrating gene expression and ChIP-chip
      data, we develop a method, called MOdule Finding Algorithm (MOFA), for
      reconstructing TRMs of the yeast cell cycle. MOFA identified 87 TRMs, which
      together contain 336 distinct genes regulated by 40 TFs. Using various kinds of
      data, we validated the biological relevance of the identified TRMs. Our analysis
      shows that different combinations of a fairly small number of TFs are responsible
      for regulating a large number of genes involved in different cell cycle phases
      and that there may exist crosstalk between the cell cycle and other cellular
      processes. MOFA is capable of finding many novel TF-target gene relationships and
      can determine whether a TF is an activator or/and a repressor. Finally, MOFA
      refines some clusters proposed by previous studies and provides a better
      understanding of how the complex expression program of the cell cycle is
      regulated. CONCLUSION: MOFA was developed to reconstruct TRMs of the yeast cell
      cycle. Many of these TRMs are in agreement with previous studies. Further, MOFA
      inferred many interesting modules and novel TF combinations. We believe that
      computational analysis of multiple types of data will be a powerful approach to
      studying complex biological systems when more and more genomic resources such as
      genome-wide protein activity data and protein-protein interaction data become
      available.

PMID- 17010189
TI  - Analysis with respect to instrumental variables for the exploration of microarray
      data structures.
AB  - BACKGROUND: Evaluating the importance of the different sources of variations is
      essential in microarray data experiments. Complex experimental designs generally
      include various factors structuring the data which should be taken into account.
      The objective of these experiments is the exploration of some given factors while
      controlling other factors. RESULTS: We present here a family of methods, the
      analyses with respect to instrumental variables, which can be easily applied to
      the particular case of microarray data. An illustrative example of analysis with
      instrumental variables is given in the case of microarray data investigating the
      effect of beverage intake on peripheral blood gene expression. This approach is
      compared to an ANOVA-based gene-by-gene statistical method. CONCLUSION:
      Instrumental variables analyses provide a simple way to control several sources
      of variation in a multivariate analysis of microarray data. Due to their
      flexibility, these methods can be associated with a large range of ordination
      techniques combined with one or several qualitative and/or quantitative
      descriptive variables.

PMID- 17010190
TI  - Perforated carcinoma of the caecum presenting as necrotising fasciitis of the
      abdominal wall, the key to early diagnosis and management.
AB  - BACKGROUND: Necrotising Fasciitis is a life threatening soft tissue infection
      which requires aggressive, early surgical management. CASE PRESENTATION: We
      present a rare case of a retroperitoneal perforation of a carcinoma of the caecum
      presenting as a necrotising fasciitis of the anterior abdominal wall. CONCLUSION:
      This case highlights the importance of early aggressive debridement to healthy
      tissue limits, the consideration of a rare underlying cause, and the scope for
      plastic surgical reconstruction in order that aggressive initial surgery can be
      adequately performed.

PMID- 17010191
TI  - Direct microvascular monitoring of a free autologous jejunal flap using
      microendoscopy: a case report.
AB  - BACKGROUND: Early identification of flap failure is an indispensable prerequisite
      for flap salvage. Although many technical developments of free flap monitoring
      have now reached clinical application, very few are considered to be reliable and
      non-invasive for early recognition of flap failure. CASE PRESENTATION: We used
      microendoscopic technique for microvascular monitoring of free autologous jejunal
      flap by the direct visualisation of the flow of erythrocytes through the
      capillary vasculature on both the mucosal and serosal surfaces. Blood flow was
      seen to be pulsatile, with individual erythrocytes visible in the capillaries.
      The best view was obtained when the scope was focussed directly on the capillary
      rather than the graft surface. The view of the unstained mucosal surface was
      bland apart from the fine capillary loops which were seen to fill with each
      pulsatile event. The microendoscopic examination of the serosal surface revealed
      much larger calibre vessels with obvious blood flow. CONCLUSION: The
      microendoscopic monitoring technique is simple and safe with direct visualisation
      of blood flow. The technique may also be useful for the monitoring of other free
      bowel transplants.

PMID- 17010192
TI  - Evaluation of BacLite Rapid MRSA, a rapid culture based screening test for the
      detection of ciprofloxacin and methicillin resistant S. aureus (MRSA) from
      screening swabs.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major
      nosocomial pathogen worldwide. The need for accurate and rapid screening methods
      to detect MRSA carriers has been clearly established. The performance of a novel
      assay, BacLite Rapid MRSA (Acolyte Biomedica, UK) for the rapid detection (5 h)
      and identification of hospital associated ciprofloxacin resistant strains of MRSA
      directly from nasal swab specimens was compared to that obtained by culture on
      Mannitol salt agar containing Oxacillin (MSAO) after 48 h incubation. RESULTS: A
      total of 1382 nasal screening swabs were tested by multiple operators. The
      BacLite Rapid MRSA test detected 142 out of the 157 confirmed MRSA that were
      detected on MSAO giving a diagnostic sensitivity of 90.4, diagnostic specificity
      of 95.7% and a negative predictive value of 98.7%. Of the 15 false negatives
      obtained by the BacLite Rapid MRSA test, seven grew small amounts (< 10 colonies
      of MRSA) on the MSAO culture plate and five isolates were ciprofloxacin
      sensitive. However there were 13 confirmed BacLite MRSA positive samples, which
      were negative by the direct culture method, probably due to overgrowth on the
      MSAO plate. There were 53 false positive results obtained by the BacLite Rapid
      MRSA test at 5 h and 115 cases where MRSA colonies were tentatively identified on
      the MSAO plate when read at 48 h, and which subsequently proved not to be MRSA.
      CONCLUSION: The BacLite MRSA test is easy to use and provides a similar level of
      sensitivity to conventional culture for the detection of nasal carriage of MRSA
      with the advantage that the results are obtained much more rapidly.

PMID- 17010193
TI  - Mutation analysis and characterization of ATR sequence variants in breast cancer
      cases from high-risk French Canadian breast/ovarian cancer families.
AB  - BACKGROUND: Ataxia telangiectasia-mutated and Rad3-related (ATR) is a member of
      the PIK-related family which plays, along with ATM, a central role in cell-cycle
      regulation. ATR has been shown to phosphorylate several tumor suppressors like
      BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer
      susceptibility gene and the current study was designed to screen for ATR germline
      mutations potentially involved in breast cancer predisposition. METHODS: ATR
      direct sequencing was performed using a fluorescent method while widely available
      programs were used for linkage disequilibrium (LD), haplotype analyses, and
      tagging SNP (tSNP) identification. Expression analyses were carried out using
      real-time PCR. RESULTS: The complete sequence of all exons and flanking intronic
      sequences were analyzed in DNA samples from 54 individuals affected with breast
      cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families.
      Although no germline mutation has been identified in the coding region, we
      identified 41 sequence variants, including 16 coding variants, 3 of which are not
      reported in public databases. SNP haplotypes were established and tSNPs were
      identified in 73 healthy unrelated French Canadians, providing a valuable tool
      for further association studies involving the ATR gene, using large cohorts. Our
      analyses led to the identification of two novel alternative splice transcripts.
      In contrast to the transcript generated by an alternative splicing site in the
      intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is
      widely expressed, at significant but relatively low levels, in both normal and
      tumoral cells including normal breast and ovarian tissue. CONCLUSION: Although no
      deleterious mutations were identified in the ATR gene, the current study provides
      an haplotype analysis of the ATR gene polymorphisms, which allowed the
      identification of a set of SNPs that could be used as tSNPs for large-scale
      association studies. In addition, our study led to the characterization of a
      novel Delta33 splice form, which could generate a putative truncated protein
      lacking several functional domains. Additional studies in large cohorts and other
      populations will be needed to further evaluate if common and/or rare ATR sequence
      variants can be associated with a modest or intermediate breast cancer risk.

PMID- 17010194
TI  - Suckling a protein-restricted rat dam leads to diminished albuminuria in her male
      offspring in adult life: a longitudinal study.
AB  - BACKGROUND: Previous studies have shown that in male rats, exposure to maternal
      protein restriction either in utero or whilst suckling can have profound effects
      on both longevity and kidney telomere lengths. This study monitored albuminuria
      longitudinally in male rats whose mothers had been protein restricted either
      during pregnancy or lactation. METHODS: Pregnant Wistar rats were fed either a
      20% ('control') or an 8% protein ('low protein') diet. At two days of age some of
      the pups were cross-fostered to dams fed the diet that was not given to their
      biological mothers. At weaning all pups were fed standard chow. Urine samples
      were collected for the measurement of albumin and creatinine at monthly intervals
      from two months-of-age. Longitudinal analysis was then performed using repeated
      measures analysis of variance. RESULTS: Overall estimated marginal geometric mean
      (95 % confidence interval) urine albumin to creatinine ratios were: control
      animals 79.5 (57.2 to approximately 110.6) g/mol (n = 6 litters, 24 animals in
      total), those exposed in utero to maternal protein restriction 71.0 (47.4 to
      approximately 106.5) (n = 4 litters, 16 animals in total), those exposed to
      maternal protein restriction whilst suckling 21.2 (14.7 to approximately 30.4) (n
      = 5 litters, 20 animals in total) (p < 0.001). These latter animals had lower
      albumin to creatinine ratios than either of the two other groups (both p <
      0.001), which had ratios that were indistinguishable from each other (p = 1.0).
      Similar results were gained using 24 h. urine albumin excretion rates. These
      differences became evident from three months-of-age and were long-lasting.
      CONCLUSION: Animals exposed to maternal protein restriction whilst suckling
      exhibited lower urine albumin excretions during much of adult life. As urine
      albumin can be nephrotoxic, these rats therefore appeared to be relatively
      protected against future nephron damage like that previously observed in animals
      exposed to maternal protein restriction in utero.

PMID- 17010195
TI  - Disparities in preventive procedures: comparisons of self-report and Medicare
      claims data.
AB  - BACKGROUND: Racial/ethnic disparities are assessed using either self-report or
      claims data. We compared these two data sources and examined contributors to
      discrepancies in estimates of disparities. METHODS: We analyzed self-report and
      matching claims data from Medicare Beneficiaries 65 and older who participated in
      the Medicare Current Beneficiary Survey, 1999-2002. Six preventive procedures
      were included: PSA testing, influenza vaccination, Pap smear testing, cholesterol
      testing, mammography, and colorectal cancer testing. We examined predictors of
      self-reports in the absence of claims and claims in the absence of self-reports.
      RESULTS: With the exception of PSA testing, racial/ethnic disparities in
      preventive procedures are generally larger when using Medicare claims than when
      using patients' self-report. Analyses adjusting for age, gender, income,
      educational level, health status, proxy response and supplemental insurance
      showed that minorities were more likely to self-report preventive procedures in
      the absence of claims. Adjusted odds ratios ranged from 1.07 (95% CI: 0.88 -
      1.30) for PSA testing to 1.83 (95% CI: 1.46 - 2.30) for Pap smear testing. Rates
      of claims in the absence of self-report were low. Minorities were more likely to
      have PSA test claims in the absence of self-reports (1.55 95% CI: 1.17 - 2.06),
      but were less likely to have influenza vaccination claims in the absence of self
      reports (0.69 95% CI: 0.51 - 0.93). CONCLUSION: These findings are consistent
      with either racial/ethnic reporting biases in receipt of preventive procedures or
      less efficient Medicare billing among providers with large minority practices.

PMID- 17010196
TI  - Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing
      by-synthesis approach.
AB  - BACKGROUND: High throughput sequencing-by-synthesis is an emerging technology
      that allows the rapid production of millions of bases of data. Although the
      sequence reads are short, they can readily be used for re-sequencing. By re
      sequencing the mRNA products of a cell, one may rapidly discover polymorphisms
      and splice variants particular to that cell. RESULTS: We present the utility of
      massively parallel sequencing by synthesis for profiling the transcriptome of a
      human prostate cancer cell-line, LNCaP, that has been treated with the synthetic
      androgen, R1881. Through the generation of approximately 20 megabases (MB) of EST
      data, we detect transcription from over 10,000 gene loci, 25 previously
      undescribed alternative splicing events involving known exons, and over 1,500
      high quality single nucleotide discrepancies with the reference human sequence.
      Further, we map nearly 10,000 ESTs to positions on the genome where no
      transcription is currently predicted to occur. We also characterize various
      obstacles with using sequencing by synthesis for transcriptome analysis and
      propose solutions to these problems. CONCLUSION: The use of high-throughput
      sequencing-by-synthesis methods for transcript profiling allows the specific and
      sensitive detection of many of a cell's transcripts, and also allows the
      discovery of high quality base discrepancies, and alternative splice variants.
      Thus, this technology may provide an effective means of understanding various
      disease states, discovering novel targets for disease treatment, and discovery of
      novel transcripts.

PMID- 17010197
TI  - Analysis of in vitro replicated human hepatitis C virus (HCV) for the
      determination of genotypes and quasispecies.
AB  - Isolation and self-replication of infectious HCV has been a difficult task.
      However, this is needed for the purposes of developing rational drugs and for the
      analysis of the natural virus. Our recent report of an in vitro system for the
      isolation of human HCV from infected patients and their replication in tissue
      culture addresses this challenge. At California Institute of Molecular Medicine
      several isolates of HCV, called CIMM-HCV, were grown for over three years in cell
      culture. This is a report of the analysis of CIMM-HCV isolates for subtypes and
      quasispecies using a 269 bp segment of the 5'UTR. HCV RNA from three patients and
      eleven CIMM-HCV were analyzed for this purpose. All isolates were essentially
      identical. Isolates of HCV from one patient were serially transmitted into fresh
      cells up to eight times and the progeny viruses from each transmission were
      compared to each other and also to the primary isolates from the patient's serum.
      Some isolates were also transmitted to different cell types, while others were
      cultured continuously without retransmission for over three years. We noted minor
      sequence changes when HCV was cultured for extended periods of time. HCV in T
      cells and non-committed lymphoid cells showed a few differences when compared to
      isolates obtained from immortalized B-cells. These viruses maintained close
      similarity despite repeated transmissions and passage of time. There were no
      subtypes or quasispecies noted in CIMM-HCV.

PMID- 17010198
TI  - Discovery of significant variants containing large deletions in the 5'UTR of
      human hepatitis C virus (HCV).
AB  - We recently reported the isolation and in vitro replication of hepatitis C virus.
      These isolates were termed CIMM-HCV and analyzed to establish genotypes and
      subtypes, which are reported elsewhere. During this analysis, an HCV isolated
      from a patient was discovered that had large deletions in the 5'UTR. 57% of the
      HCV RNA found in this patient's sera had 113 or 116 bp deletions. Sequence data
      showed that domains IIIa to IIIc were missing. Previous studies have suggested
      that these domains may be important for translation. In vitro replicated HCV from
      this patient did not contain these deletions, however, it contained a 148 bp
      deletion in the 5'UTR. Whereas the patient HCV lacked domains IIIa through IIIc,
      the isolate lacked domains IIIa through IIId. HCV from this patient continues to
      produce large deletions in vitro, suggesting that the deletion may not be
      important for the assembly or replication of the virus. This is the first report
      describing these large deletions.

PMID- 17010199
TI  - Patterns of expansion and expression divergence in the plant polygalacturonase
      gene family.
AB  - BACKGROUND: Polygalacturonases (PGs) belong to a large gene family in plants and
      are believed to be responsible for various cell separation processes. PG
      activities have been shown to be associated with a wide range of plant
      developmental programs such as seed germination, organ abscission, pod and anther
      dehiscence, pollen grain maturation, fruit softening and decay, xylem cell
      formation, and pollen tube growth, thus illustrating divergent roles for members
      of this gene family. A close look at phylogenetic relationships among Arabidopsis
      and rice PGs accompanied by analysis of expression data provides an opportunity
      to address key questions on the evolution and functions of duplicate genes.
      RESULTS: We found that both tandem and whole-genome duplications contribute
      significantly to the expansion of this gene family but are associated with
      substantial gene losses. In addition, there are at least 21 PGs in the common
      ancestor of Arabidopsis and rice. We have also determined the relationships
      between Arabidopsis and rice PGs and their expression patterns in Arabidopsis to
      provide insights into the functional divergence between members of this gene
      family. By evaluating expression in five Arabidopsis tissues and during five
      stages of abscission, we found overlapping but distinct expression patterns for
      most of the different PGs. CONCLUSION: Expression data suggest specialized roles
      or subfunctionalization for each PG gene member. PGs derived from whole genome
      duplication tend to have more similar expression patterns than those derived from
      tandem duplications. Our findings suggest that PG duplicates underwent rapid
      expression divergence and that the mechanisms of duplication affect the
      divergence rate.

PMID- 17010200
TI  - Plasma levels of leptin and mammographic density among postmenopausal women: a
      cross-sectional study.
AB  - INTRODUCTION: Obesity has been linked to increased risk of breast cancer in
      postmenopausal women. Increased peripheral production of estrogens has been
      regarded as the main cause for this association, but other features of increased
      body fat mass may also play a part. Leptin is a protein produced mainly by
      adipose tissue and may represent a growth factor in cancer. We examined the
      association between leptin plasma levels and mammographic density, a biomarker
      for breast cancer risk. METHODS: We included data from postmenopausal women aged
      55 and older, who participated in a cross-sectional mammography study in Tromso,
      Norway. Mammograms, plasma leptin measurements as well as information on
      anthropometric and hormonal/reproductive factors were available from 967 women.
      We assessed mammographic density using a previously validated computer-assisted
      method. Multiple linear regression analysis was applied to investigate the
      association between mammographic density and quartiles of plasma leptin
      concentration. Because we hypothesized that the effect of leptin on mammographic
      density could vary depending on the amount of nondense or fat tissue in the
      breast, we also performed analyses on plasma leptin levels and mammographic
      density within tertiles of mammographic nondense area. RESULTS: After adjusting
      for age, postmenopausal hormone use, number of full-term pregnancies and age of
      first birth, there was an inverse association between leptin and absolute
      mammographic density (P(trend) = 0.001). When we additionally adjusted for body
      mass index and mammographic nondense area, no statistically significant
      association between plasma leptin and mammographic density was found (P(trend) =
      0.16). Stratified analyses suggested that the association between plasma leptin
      and mammographic density could differ with the amount of nondense area of the
      mammogram, with the strongest association between leptin and mammographic
      absolute density in the stratum with the medium breast fat content (P(trend) =
      0.003, P for interaction = 0.05). CONCLUSION: We found no overall consistent
      association between the plasma concentration of leptin and absolute mammographic
      density. Although weak, there was some suggestion that the association between
      leptin and mammographic density could differ with the amount of fat tissue in the
      breast.

PMID- 17010202
TI  - Hernia fibroblasts lack beta-estradiol-induced alterations of collagen gene
      expression.
AB  - BACKGROUND: Estrogens are reported to increase type I and type III collagen
      deposition and to regulate Metalloproteinase 2 (MMP-2) expression. These proteins
      are reported to be dysregulated in incisional hernia formation resulting in a
      significantly decreased type I to III ratio. We aimed to evaluate the beta
      estradiol mediated regulation of type I and type III collagen genes as well as
      MMP-2 gene expression in fibroblasts derived from patients with or without
      history of recurrent incisional hernia disease. We compared primary fibroblast
      cultures from male/female subjects without/without incisional hernia disease.
      RESULTS: Incisional hernia fibroblasts (IHFs) revealed a decreased type I/III
      collagen mRNA ratio. Whereas fibroblasts from healthy female donors responded to
      beta-estradiol, type I and type III gene transcription is not affected in
      fibroblasts from males or affected females. Furthermore beta-estradiol had no
      influence on the impaired type I to III collagen ratio in fibroblasts from
      recurrent hernia patients. CONCLUSION: Our results suggest that beta-estradiol
      does not restore the imbaired balance of type I/III collagen in incisional hernia
      fibroblasts. Furthermore, the individual was identified as an independent factor
      for the beta-estradiol induced alterations of collagen gene expression. The
      observation of gender specific beta-estradiol-dependent changes of collagen gene
      expression in vitro is of significance for future studies of cellular response.

PMID- 17010201
TI  - Eye and neural defects associated with loss of GDF6.
AB  - BACKGROUND: In Xenopus the bone morphogenetic protein growth and differentiation
      factor 6 (GDF6) is expressed at the edge of the neural plate, and within the
      anterior neural plate including the eye fields. Here we address the role of GDF6
      in neural and eye development by morpholino knockdown experiments. RESULTS: We
      show that depletion of GDF6 (BMP13) resulted in a reduction in eye size, loss of
      laminar structure and a reduction in differentiated neural cell types within the
      retina. This correlated with a reduction in staining for Smad1/5/8
      phosphorylation indicating a decrease in GDF6 signalling through loss of
      phosphorylation of these intracellular mediators of bone morphogenetic protein
      (BMP) signalling. In addition, the Pax6 expression domain is reduced in size at
      early optic vesicle stages. Neural cell adhesion molecule (NCAM) is generally
      reduced in intensity along the neural tube, while in the retina and brain
      discreet patches of NCAM expression are also lost. GDF6 knock down resulted in an
      increase in cell death along the neural tube and within the retina as determined
      by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      staining. CONCLUSION: Our data demonstrate that GDF6 has an important role in
      neural differentiation in the eye as well as within the central nervous system,
      and that GDF6 may act in some way to maintain cell survival within the ectoderm,
      during the normal waves of programmed cell death.

PMID- 17010203
TI  - Do functional walk tests reflect cardiorespiratory fitness in sub-acute stroke?
AB  - BACKGROUND AND PURPOSE: The Six-Minute Walk Test (6MWT) has been employed as a
      measure of functional capacity, but its relationship to cardiorespiratory fitness
      in stroke is not well established. Gait speed measured over short distances is
      commonly used as an index of walking competency following stroke. We evaluated
      the relationship between the 6MWT, aerobic fitness (VO2peak) and walking
      competency in sub-acute stroke. METHODS: Thirty-six individuals (mean age +/- SD,
      64.6 +/- 14.4 years; time post-stroke 16.2 +/- 13.3 days) were evaluated using
      the 6MWT (distance, speed, heart rate), a maximal exercise test (VO2peak, heart
      rate, exercise test duration), and walking competency using a five meter walk
      (speed, symmetry ratio). Correlation analyses were used to examine the
      relationships between these outcomes. RESULTS: There was a strong correlation
      between the 6MWT and five meter walk velocity for preferred (r = 0.79) and fast
      (r = 0.82) speed (p < 0.001). On average, the 6MWT speed was faster than the
      preferred gait speed (94.9 cm/s vs. 83.8 cm/s, p = 0.003), but slower than the
      fast-paced walk (115.1 cm/s, p < 0.001). There was significant though more
      moderate association between 6MWT distance and VO2peak (r = 0.56, p < 0.001) and
      exercise test duration (r = 0.60, p < 0.001). CONCLUSION: The speed selected
      during the 6MWT was strongly related to the velocities selected during the five
      meter walk distance (intermediate to the selected preferred and fast speeds).
      Although the 6MWT may be challenging to the cardiorespiratory system, it appears
      to be more strongly influenced by potential limits to walking speed rather than
      cardiorespiratory capacity. As a result, this test is not, by itself, an adequate
      measure of aerobic fitness early after stroke.

PMID- 17010204
TI  - The ethnoecology of Caicara metapopulations (Atlantic Forest, Brazil): ecological
      concepts and questions.
AB  - The Atlantic Forest is represented on the coast of Brazil by approximately 7.5%
      of remnants, much of these concentrated on the country's SE coast. Within these
      southeastern remnants, we still find the coastal Caicaras who descend from Native
      Indians and Portuguese Colonizers. The maintenance of such populations, and their
      existence in spite of the deforestation that occurred on the Atlantic Forest
      coast, deserves special attention and analysis. In this study, I address, in
      particular, the Caicaras who live on the coast of Sao Paulo and Rio de Janeiro
      States, illustrating with examples of coastal inhabitants from other areas, such
      as Bahia State (NE coast) and of other forested areas (riverine caboclos of the
      Amazon). The major focus of this study, based on previous research, performed
      since 1986 in several populations or villages of the Atlantic Forest coast, is to
      understand the resilience of the Caicaras, which is analyzed using ecological
      concepts, such as metapopulation, resilience and adaptive cycles. The Caicara
      populations are located on islands (Buzios, Comprida, Grande, Ilhabela, Jaguanum,
      Gipoia) and on the coast (Bertioga, Puruba, Picinguaba, among others).
      Information gathered about the Caicaras regarding the economic cycles of the
      local regions, along with ecological, historical and economic data available, are
      used to understand such resilience, and are complemented with comparative
      examples from the Brazilian Amazon and with variables such as the local
      restrictions imposed by environmental governmental agencies.

PMID- 17010205
TI  - Airway smooth muscle as a target of asthma therapy: history and new directions.
AB  - Ultimately, asthma is a disease characterized by constriction of airway smooth
      muscle (ASM). The earliest approach to the treatment of asthma comprised the use
      of xanthines and anti-cholinergics with the later introduction of anti-histamines
      and anti-leukotrienes. Agents directed at ion channels on the smooth muscle
      membrane (Ca2+ channel blockers, K+ channel openers) have been tried and found to
      be ineffective. Functional antagonists, which modulate intracellular signalling
      pathways within the smooth muscle (beta-agonists and phosphodiesterase
      inhibitors), have been used for decades with success, but are not universally
      effective and patients continue to suffer with exacerbations of asthma using
      these drugs. During the past several decades, research energies have been
      directed into developing therapies to treat airway inflammation, but there have
      been no substantial advances in asthma therapies targeting the ASM. In this
      manuscript, excitation-contraction coupling in ASM is addressed, highlighting the
      current treatment of asthma while proposing several new directions that may prove
      helpful in the management of this disease.

PMID- 17010206
TI  - Loss of the flagellum happened only once in the fungal lineage: phylogenetic
      structure of kingdom Fungi inferred from RNA polymerase II subunit genes.
AB  - BACKGROUND: At present, there is not a widely accepted consensus view regarding
      the phylogenetic structure of kingdom Fungi although two major phyla, Ascomycota
      and Basidiomycota, are clearly delineated. Regarding the lower fungi, Zygomycota
      and Chytridiomycota, a variety of proposals have been advanced. Microsporidia may
      or may not be fungi; the Glomales (vesicular-arbuscular mycorrhizal fungi) may or
      may not constitute a fifth fungal phylum, and the loss of the flagellum may have
      occurred either once or multiple times during fungal evolution. All of these
      issues are capable of being resolved by a molecular phylogenetic analysis which
      achieves strong statistical support for major branches. To date, no fungal
      phylogeny based upon molecular characters has satisfied this criterion. RESULTS:
      Using the translated amino acid sequences of the RPB1 and RPB2 genes, we have
      inferred a fungal phylogeny that consists largely of well-supported monophyletic
      phyla. Our major results, each with significant statistical support, are: (1)
      Microsporidia are sister to kingdom Fungi and are not members of Zygomycota; that
      is, Microsporidia and fungi originated from a common ancestor. (2)
      Chytridiomycota, the only fungal phylum having a developmental stage with a
      flagellum, is paraphyletic and is the basal lineage. (3) Zygomycota is
      monophyletic based upon sampling of Trichomycetes, Zygomycetes, and Glomales. (4)
      Zygomycota, Basidiomycota, and Ascomycota form a monophyletic group separate from
      Chytridiomycota. (5) Basidiomycota and Ascomycota are monophyletic sister groups.
      CONCLUSION: In general, this paper highlights the evolutionary position and
      significance of the lower fungi (Zygomycota and Chytridiomycota). Our results
      suggest that loss of the flagellum happened only once during early stages of
      fungal evolution; consequently, the majority of fungi, unlike plants and animals,
      are nonflagellated. The phylogeny we infer from gene sequences is the first one
      that is congruent with the widely accepted morphology-based classification of
      Fungi. We find that, contrary to what has been published elsewhere, the four
      morphologically defined phyla (Ascomycota, Basidiomycota, Zygomycota and
      Chytridiomycota) do not overlap with one another. Microsporidia are not included
      within kingdom Fungi; rather they are a sister-group to the Fungi. Our study
      demonstrates the applicability of protein sequences from large, slowly-evolving
      genes to the derivation of well-resolved and highly supported phylogenies across
      long evolutionary distances.

PMID- 17010207
TI  - Identification of estrogen-regulated genes by microarray analysis of the uterus
      of immature rats exposed to endocrine disrupting chemicals.
AB  - Environmental estrogenic compounds which bind to the estrogen receptor (ER) can
      block or alter endogenous functions of estrogen in reproductive and developmental
      stages. A microarray technology is a very valuable method for the prediction of
      hormone-responsive activities in various gene expressions. Thus, we investigated
      the altered gene expression by estrogen and endocrine disruptors (EDs) using
      microarray technology in the uterus of immature rats. In this study, the
      expression levels of only 555 genes (7.42%) among the 7636 genes spotted on
      microarray chips were enhanced by more than two-fold following treatment with
      estradiol (E2), suggesting that direct or rapid response to E2 is widespread at
      the mRNA levels in these genes. In addition, elevated expression levels of the
      genes (over 2-fold) were observed by diethylstilbestrol (DES; 9.01%), octyl
      phenol (OP; 8.81%), nonyl-phenol (NP; 9.51%), bisphenol-A (BPA; 8.26%) or
      genistein (9.97%) in the uterus of immature rats. The expression levels of
      representative genes, i.e., calbindin-D9k (CaBP-9k; vitamin D-dependent calcium
      binding protein), oxytocin, adipocyte complement related protein (MW 30 kDa),
      lactate dehydrogenase A and calcium binding protein A6 (S100a6; calcyclin), were
      confirmed in these tissues by real-time PCR. In addition, the mRNA levels of
      these genes by real-time PCR were increased at follicular phase when E2 level was
      elevated during estrous cycle of adult female rats. In conclusion, these results
      indicate distinct altered expression of responsive genes following exposure to E2
      and estrogenic compounds, and implicate distinct effects of endogenous E2 and
      environmental endocrine disrupting chemicals in the uterus of immature rats.

PMID- 17010208
TI  - Eukaryotic initiation factor 4E (eIF4E) and angiogenesis: prognostic markers for
      breast cancer.
AB  - BACKGROUND: The overexpression of eukaryotic translation initiation factor 4E
      (eIF4E), a key regulator of protein synthesis, is involved in the malignant
      progression of human breast cancer. This study investigates the relationship
      between eIF4E and angiogenesis, as well as their prognostic impact in patients
      with human breast cancer. METHODS: Immunohistochemical staining was used to
      determine protein expression of eIF4E, vascular endothelial growth factor (VEGF),
      interleukin-8 (IL-8), and CD105 in a set of 122 formalin-fixed, paraffin-embedded
      primary breast cancer tissues. Expression of eIF4E in positive cells was
      characterized by cytoplasmic staining. Evaluation of VEGF and IL-8 in the same
      tissue established the angiogenic profiles, while CD105 was used as an indicator
      of microvessel density (MVD). RESULTS: A significant relationship was found
      between the level of eIF4E expression and histological grade (P = 0.016). VEGF,
      IL-8, and MVD were closely related to tumor grade (P = 0.003, P = 0.022, and P <
      0.001, respectively) and clinical stage (P = 0.007, P = 0.048, and P < 0.001,
      respectively). Expression of eIF4E was also significantly correlated with VEGF (P
      = 0.007), IL-8 (P = 0.007), and MVD (P = 0.006). Patients overexpressing eIF4E
      had significantly worse overall (P = 0.01) and disease-free survival (P = 0.006).
      When eIF4E, histological grade, tumor stage, ER, PR, Her-2 status and the levels
      of VEGF, IL-8, MVD were included in a multivariate Cox regression analysis, eIF4E
      emerged as an independent prognostic factor for breast cancer (P = 0.001), along
      with stage (P = 0.005), node status (P = 0.046), and MVD (P = 0.004). CONCLUSION:
      These results suggest that higher eIF4E expression correlates with both
      angiogenesis and vascular invasion of cancer cells, and could therefore serve as
      a useful histological predictor for less favorable outcome in breast cancer
      patients, as well as represent a potential therapeutic target.

PMID- 17010209
TI  - Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced
      hepatic and renal disorders.
AB  - BACKGROUND: Carbon tetrachloride (CCl4) is a well-known hepatotoxin and exposure
      to this chemical is known to induce oxidative stress and causes liver injury by
      the formation of free radicals. Acute and chronic renal damage are also very
      common pathophysiologic disturbances caused by CCl4. The present study has been
      conducted to evaluate the protective role of the aqueous extract of the bark of
      Termnalia arjuna (TA), an important Indian medicinal plant widely used in the
      preparation of ayurvedic formulations, on CCl4 induced oxidative stress and
      resultant dysfunction in the livers and kidneys of mice. METHODS: Animals were
      pretreated with the aqueous extract of TA (50 mg/kg body weight) for one week and
      then challenged with CCl4 (1 ml/kg body weight) in liquid paraffin (1:1, v/v) for
      2 days. Serum marker enzymes, namely, glutamate pyruvate transaminase (GPT) and
      alkaline phosphatase (ALP) were estimated in the sera of all study groups.
      Antioxidant status in both the liver and kidney tissues were estimated by
      determining the activities of the antioxidative enzymes, superoxide dismutase
      (SOD), catalase (CAT) and glutathione-S-transferase (GST); as well as by
      determining the levels of thiobarbutaric acid reactive substances (TBARS) and
      reduced glutathione (GSH). In addition, free radical scavenging activity of the
      extract was determined from its DPPH radical quenching ability. RESULTS: Results
      showed that CCl4 caused a marked rise in serum levels of GPT and ALP. TBARS level
      was also increased significantly whereas GSH, SOD, CAT and GST levels were
      decreased in the liver and kidney tissue homogenates of CCl4 treated mice.
      Aqueous extract of TA successfully prevented the alterations of these effects in
      the experimental animals. Data also showed that the extract possessed strong free
      radical scavenging activity comparable to that of vitamin C. CONCLUSION: Our
      study demonstrated that the aqueous extract of the bark of TA could protect the
      liver and kidney tissues against CCl4-induced oxidative stress probably by
      increasing antioxidative defense activities.

PMID- 17010210
TI  - A novel mutation in STK11 gene is associated with Peutz-Jeghers Syndrome in
      Indian patients.
AB  - BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare multi-organ cancer syndrome
      and understanding its genetic basis may help comprehend the molecular mechanism
      of familial cancer. A number of germ line mutations in the STK11 gene, encoding a
      serine threonine kinase have been reported in these patients. However, STK11
      mutations do not explain all PJS cases. An earlier study reported absence of
      STK11 mutations in two Indian families and suggested another potential locus on
      19q13.4 in one of them. METHODS: We sequenced the promoter and the coding region
      including the splice-site junctions of the STK11 gene in 16 affected members from
      ten well-characterized Indian PJS families with a positive family history.
      RESULTS: We did not observe any of the reported mutations in the STK11 gene in
      the index patients from these families. We identified a novel pathogenic mutation
      (c.790_793 delTTTG) in the STK11 gene in one index patient (10%) and three
      members of his family. The mutation resulted in a frame-shift leading to
      premature termination of the STK11 protein at 286th codon, disruption of kinase
      domain and complete loss of C-terminal regulatory domain. Based on these results,
      we could offer predictive genetic testing, prenatal diagnosis and genetic
      counselling to other members of the family. CONCLUSION: Ours is the first study
      reporting the presence of STK11 mutation in Indian PJS patients. It also suggests
      that reported mutations in the STK11 gene are not responsible for the disease and
      novel mutations also do not account for many Indian PJS patients. Large-scale
      genomic deletions in the STK11 gene or another locus may be associated with the
      PJS phenotype in India and are worth future investigation.

PMID- 17010211
TI  - High-resolution quantitative imaging of mammalian and bacterial cells using
      stable isotope mass spectrometry.
AB  - BACKGROUND: Secondary-ion mass spectrometry (SIMS) is an important tool for
      investigating isotopic composition in the chemical and materials sciences, but
      its use in biology has been limited by technical considerations. Multi-isotope
      imaging mass spectrometry (MIMS), which combines a new generation of SIMS
      instrument with sophisticated ion optics, labeling with stable isotopes, and
      quantitative image-analysis software, was developed to study biological
      materials. RESULTS: The new instrument allows the production of mass images of
      high lateral resolution (down to 33 nm), as well as the counting or imaging of
      several isotopes simultaneously. As MIMS can distinguish between ions of very
      similar mass, such as 12C15N- and 13C14N-, it enables the precise and
      reproducible measurement of isotope ratios, and thus of the levels of enrichment
      in specific isotopic labels, within volumes of less than a cubic micrometer. The
      sensitivity of MIMS is at least 1,000 times that of 14C autoradiography. The
      depth resolution can be smaller than 1 nm because only a few atomic layers are
      needed to create an atomic mass image. We illustrate the use of MIMS to image
      unlabeled mammalian cultured cells and tissue sections; to analyze fatty-acid
      transport in adipocyte lipid droplets using 13C-oleic acid; to examine nitrogen
      fixation in bacteria using 15N gaseous nitrogen; to measure levels of protein
      renewal in the cochlea and in post-ischemic kidney cells using 15N-leucine; to
      study DNA and RNA co-distribution and uridine incorporation in the nucleolus
      using 15N-uridine and 81Br of bromodeoxyuridine or 14C-thymidine; to reveal
      domains in cultured endothelial cells using the native isotopes 12C, 16O, 14N and
      31P; and to track a few 15N-labeled donor spleen cells in the lymph nodes of the
      host mouse. CONCLUSION: MIMS makes it possible for the first time to both image
      and quantify molecules labeled with stable or radioactive isotopes within
      subcellular compartments.

PMID- 17010212
TI  - The complete chloroplast genome sequence of Citrus sinensis (L.) Osbeck var
      'Ridge Pineapple': organization and phylogenetic relationships to other
      angiosperms.
AB  - BACKGROUND: The production of Citrus, the largest fruit crop of international
      economic value, has recently been imperiled due to the introduction of the
      bacterial disease Citrus canker. No significant improvements have been made to
      combat this disease by plant breeding and nuclear transgenic approaches.
      Chloroplast genetic engineering has a number of advantages over nuclear
      transformation; it not only increases transgene expression but also facilitates
      transgene containment, which is one of the major impediments for development of
      transgenic trees. We have sequenced the Citrus chloroplast genome to facilitate
      genetic improvement of this crop and to assess phylogenetic relationships among
      major lineages of angiosperms. RESULTS: The complete chloroplast genome sequence
      of Citrus sinensis is 160,129 bp in length, and contains 133 genes (89 protein
      coding, 4 rRNAs and 30 distinct tRNAs). Genome organization is very similar to
      the inferred ancestral angiosperm chloroplast genome. However, in Citrus the infA
      gene is absent. The inverted repeat region has expanded to duplicate rps19 and
      the first 84 amino acids of rpl22. The rpl22 gene in the IRb region has a
      nonsense mutation resulting in 9 stop codons. This was confirmed by PCR
      amplification and sequencing using primers that flank the IR/LSC boundaries.
      Repeat analysis identified 29 direct and inverted repeats 30 bp or longer with a
      sequence identity > or = 90%. Comparison of protein-coding sequences with
      expressed sequence tags revealed six putative RNA edits, five of which resulted
      in non-synonymous modifications in petL, psbH, ycf2 and ndhA. Phylogenetic
      analyses using maximum parsimony (MP) and maximum likelihood (ML) methods of a
      dataset composed of 61 protein-coding genes for 30 taxa provide strong support
      for the monophyly of several major clades of angiosperms, including monocots,
      eudicots, rosids and asterids. The MP and ML trees are incongruent in three
      areas: the position of Amborella and Nymphaeales, relationship of the magnoliid
      genus Calycanthus, and the monophyly of the eurosid I clade. Both MP and ML trees
      provide strong support for the monophyly of eurosids II and for the placement of
      Citrus (Sapindales) sister to a clade including the Malvales/Brassicales.
      CONCLUSION: This is the first complete chloroplast genome sequence for a member
      of the Rutaceae and Sapindales. Expansion of the inverted repeat region to
      include rps19 and part of rpl22 and presence of two truncated copies of rpl22 is
      unusual among sequenced chloroplast genomes. Availability of a complete Citrus
      chloroplast genome sequence provides valuable information on intergenic spacer
      regions and endogenous regulatory sequences for chloroplast genetic engineering.
      Phylogenetic analyses resolve relationships among several major clades of
      angiosperms and provide strong support for the monophyly of the eurosid II clade
      and the position of the Sapindales sister to the Brassicales/Malvales.

PMID- 17010213
TI  - Characteristics and trends in required home care by GPs in Austria: diseases and
      functional status of patients.
AB  - BACKGROUND: Almost all societies carry responsibility towards patients who
      require continuous medical care at home. In many health systems the general
      practitioner cooperates with community based services of home care and
      coordinates all medical and non medical activities. In Austria the general
      practitioner together and in cooperation with relatives of the patient and
      professional organisations usually takes on this task by visiting his patients.
      This study was carried out to identify diseases that need home care and to
      describe the functional profile of home care patients in eastern Austria.
      METHODS: Cross sectional observational study with 17 GP practices participating
      during 2 study periods in 1997 and in 2004 in eastern Austria. Each GP identified
      patients requiring home care and assessed their underlying diseases and
      functional status by filling in a questionnaire personally after an encounter.
      Patients in nursing homes were excluded. Statistical tests used were t-tests,
      contingency tables, nonparametric Wilcoxon signed rank sum test and Fisher
      combination test. RESULTS: Patients with degenerative diseases of the central
      nervous system (65%) caused by Alzheimer's disease and cerebrovascular occlusive
      disease and patients with degenerative diseases of the skeletal system (53%) were
      the largest groups among the 198 (1997) and 261 (2004) home care cases of the 11
      (1997) and 13 (2004) practices. Malignant diseases in a terminal state
      constituted only 5% of the cases. More than two thirds of all cases were female
      with an average age of 80 years. Slightly more than 70% of the patients were at
      least partially mobile. CONCLUSION: Home care and home visits for patients with
      degenerative diseases of the central nervous and skeletal system are important
      elements of GP's work. Further research should therefore focus on effective
      methods of training and rehabilitation to better the mental and physical status
      of patients living in their private homes.

PMID- 17010214
TI  - Ancient genomic architecture for mammalian olfactory receptor clusters.
AB  - BACKGROUND: Mammalian olfactory receptor (OR) genes reside in numerous genomic
      clusters of up to several dozen genes. Whole-genome sequence alignment nets of
      five mammals allow their comprehensive comparison, aimed at reconstructing the
      ancestral olfactory subgenome. RESULTS: We developed a new and general tool for
      genome-wide definition of genomic gene clusters conserved in multiple species.
      Syntenic orthologs, defined as gene pairs showing conservation of both genomic
      location and coding sequence, were subjected to a graph theory algorithm for
      discovering CLICs (clusters in conservation). When applied to ORs in five
      mammals, including the marsupial opossum, more than 90% of the OR genes were
      found within a framework of 48 multi-species CLICs, invoking a general
      conservation of gene order and composition. A detailed analysis of individual
      CLICs revealed multiple differences among species, interpretable through species
      specific genomic rearrangements and reflecting complex mammalian evolutionary
      dynamics. One significant instance involves CLIC #1, which lacks a human member,
      implying the human-specific deletion of an OR cluster, whose mouse counterpart
      has been tentatively associated with isovaleric acid odorant detection.
      CONCLUSION: The identified multi-species CLICs demonstrate that most of the
      mammalian OR clusters have a common ancestry, preceding the split between
      marsupials and placental mammals. However, only two of these CLICs were capable
      of incorporating chicken OR genes, parsimoniously implying that all other CLICs
      emerged subsequent to the avian-mammalian divergence.

PMID- 17010215
TI  - 6-Shogaol reduced chronic inflammatory response in the knees of rats treated with
      complete Freund's adjuvant.
AB  - BACKGROUND: 6-Shogaol is one of the major compounds in the ginger rhizome that
      may contribute to its anti-inflammatory properties. Confirmation of this
      contribution was sought in this study in Sprague- Dawley rats (200-250 g) treated
      with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of
      complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a
      period of 28 days. During this development of arthritis, each rat received a
      daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in
      0.2 ml peanut oil). RESULTS: Within 2 days of CFA injection, the control group
      produced maximum edematous swelling of the knee that was sustained up to the end
      of the investigation period. But, in the 6-shogaol treated group, significantly
      lower magnitudes of unsustained swelling of the knees (from 5.1 +/- 0.2 mm to 1.0
      +/- 0.2 mm, p < 0.002, n = 6) were produced during the investigation period.
      Unsustained swelling of the knees (from 3.2 +/- 0.6 mm to 0.8 +/- 1.1 mm, p <
      0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2
      mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of
      drug treatment swelling of the knees was significantly larger (11.6 +/- 2.0 mm, p
      < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats.
      This exaggerated effect in the early stage of indomethacin treatment was
      inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6
      shogaol and indomethacin were most effective in reducing swelling of the knees on
      day 28 when the controls still had maximum swelling. The effect of 6-shogaol
      compared to the controls was associated with significantly lower concentration of
      soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration
      of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial
      cavity of the knee. There was also preservation of the morphological integrity of
      the cartilage lining the femur compared to damage to this tissue in the peanut
      oil treated control group of rats. CONCLUSION: From these results, it is
      concluded that 6-shogaol reduced the inflammatory response and protected the
      femoral cartilage from damage produced in a CFA monoarthritic model of the knee
      joint of rats.

PMID- 17010216
TI  - Characteristics of HCV positive patients in an Italian urban psychiatric unit.
AB  - OBJECTIVES: 1) to assess the prevalence of hepatitis C virus (HCV) infection in a
      population of acute psychiatric in-patients; 2) to find out relationships between
      HCV comorbidity and clinical features of psychiatric patients. METHODS:
      Prospective observational study in a 6-year period. RESULTS: 2396 cases (1492
      patients) were admitted in the considered period. Forty-two patients (2.8%) were
      affected by HCV infection. HCV infection was more frequent in patients with less
      years of education, lower social class, lower last year best Global Assessment of
      Functioning score, more hostile or violent behavior in hospital, with a lifetime
      history of previous suicide attempt, and with substance-related disorders.
      CONCLUSION: HCV infection in psychiatric patients constitutes a major threat to
      the health of psychiatric patients and is related with unfavorable social
      background, worse global functioning, hostile or violent behavior, substance
      related disorders. It appears also to be a significant risk of suicidal behavior.

PMID- 17010217
TI  - Transcriptional monitoring of steady state and effects of anaerobic phases in
      chemostat cultures of the filamentous fungus Trichoderma reesei.
AB  - BACKGROUND: Chemostat cultures are commonly used in production of cellular
      material for systems-wide biological studies. We have used the novel TRAC
      (transcript analysis with aid of affinity capture) method to study expression
      stability of approximately 30 process relevant marker genes in chemostat cultures
      of the filamentous fungus Trichoderma reesei and its transformant expressing
      laccase from Melanocarpus albomyces. Transcriptional responses caused by
      transient oxygen deprivations and production of foreign protein were also studied
      in T. reesei by TRAC. RESULTS: In cultures with good steady states, the
      expression of the marker genes varied less than 20% on average between sequential
      samples for at least 5 or 6 residence times. However, in a number of T. reesei
      cultures continuous flow did not result in a good steady state. Perturbations to
      the steady state were always evident at the transcriptional level, even when they
      were not measurable as changes in biomass or product concentrations. Both
      unintentional and intentional perturbations of the steady state demonstrated that
      a number of genes involved in growth, protein production and secretion are
      sensitive markers for culture disturbances. Exposure to anaerobic conditions
      caused strong responses at the level of gene expression, but surprisingly the
      cultures could regain their previous steady state quickly, even after 3 h O2
      depletion. The main effect of producing M. albomyces laccase was down-regulation
      of the native cellulases compared with the host strain. CONCLUSION: This study
      demonstrates the usefulness of transcriptional analysis by TRAC in ensuring the
      quality of chemostat cultures prior to costly and laborious genome-wide analysis.
      In addition TRAC was shown to be an efficient tool in studying gene expression
      dynamics in transient conditions.

PMID- 17010218
TI  - Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer
      susceptibility.
AB  - There is increasing evidence identifying the crucial role of numerous dietary
      components in modifying the process of carcinogenesis. The varied effects exerted
      by nutrient and non-nutrient dietary compounds on human health and cancer risk
      are one of the new challenges for nutritional sciences. In the present paper, an
      attempt is made to review the most recent epidemiological data on interactions
      between dietary factors and metabolic gene variants in terms of cancer risk. The
      majority of case-control studies indicate the significant relationship between
      cancer risk and polymorphic xenobiotic metabolising enzymes in relation to
      dietary components. The risk of colorectal cancer is associated not only with
      CYP2E1 high-activity alleles, but also GSTA1 low-activity alleles, among
      consumers of red or processed meat. Genetic polymorphisms of NAT1 and NAT2 may be
      also a breast-cancer susceptibility factor among postmenopausal women with a high
      intake of well-done meat. On the other hand, phytochemicals, especially
      isothiocyanates, have a protective effect against colorectal and lung cancers in
      individuals lacking GST genes. Moreover, polymorphism of GSTM1 seems to be
      involved in the dietary regulation of DNA damage. The European Prospective
      Investigation into Cancer and Nutrition study shows a significant inverse
      association between the polycyclic aromatic hydrocarbon-DNA adduct level and
      dietary antioxidants only among GSTM1-null individuals. However, the absence of a
      modulatory effect of polymorphic xenobiotic metabolising enzymes and diet on the
      development of cancer has been indicated by some epidemiological investigations.
      Studies of interactions between nutrients and genes may have great potential for
      exploring mechanisms, identifying susceptible populations/individuals and making
      practical use of study results to develop preventive strategies beneficial to
      human health.

PMID- 17010219
TI  - Environmental determinants of fruit and vegetable consumption among adults: a
      systematic review.
AB  - The current ecological approach in health behaviour research recognises that
      health behaviour needs to be understood in a broad environmental context. This
      has led to an exponential increase in the number of studies on this topic. It is
      the aim of this systematic review to summarise the existing empirical evidence
      pertaining to environmental influences on fruit and vegetable (FV) consumption.
      The environment was defined as 'all factors external to the individual'.
      Scientific databases and reference lists of selected papers were systematically
      searched for observational studies among adults (18-60 years old), published in
      English between 1 January 1980 and 31 December 2004, with environmental factor(s)
      as independent factor(s), and fruit intake, vegetable intake or FV intake
      combined as one outcome measure as dependent factor(s). Findings showed there was
      a great diversity in the environmental factors studied, but that the number of
      replicated studies for each determinant was limited. Most evidence was found for
      household income, as people with lower household incomes consistently had a lower
      FV consumption. Married people had higher intakes than those who were single,
      whereas having children showed mixed results. Good local availability (e.g.
      access to one's own vegetable garden, having low food insecurity) seemed to exert
      a positive influence on intake. Regarding the development of interventions,
      improved opportunities for sufficient FV consumption among low-income households
      are likely to lead to improved intakes. For all other environmental factors, more
      replicated studies are required to examine their influence on FV intake.

PMID- 17010220
TI  - Thiamin nutrition and catalysis-induced instability of thiamin diphosphate.
AB  - Thiamin (vitamin B1) is required in animal diets because it is the precursor of
      the enzyme cofactor, thiamin diphosphate. Unlike other B vitamins, the dietary
      thiamin requirement is proportional to non-fat energy intake but there is no
      obvious biochemical reason for this relationship. In the present communication we
      show for two enzymes that the cofactor undergoes a slow destruction during
      catalysis, which may explain the interdependence of thiamin and energy intakes.

PMID- 17010221
TI  - The glycaemic effects of single doses of Panax ginseng in young healthy
      volunteers.
AB  - The results of two acute placebo-controlled, double-blind cross-over studies
      assessing the effect of Panax ginseng (G115) on blood glucose levels are
      reported. In study 1, thirty participants received three treatments: placebo; 200
      mg G115; 400 mg G115. In study 2, twenty-seven participants received four
      treatments: placebo (0 mg ginseng and 30 mg saccharin); ginseng (200 mg ginseng
      and 30 mg saccharin); placebo-glucose (0 mg ginseng and 25 g oral glucose);
      ginseng-glucose (200 mg ginseng and 25 g oral glucose). Blood glucose levels were
      measured at baseline (at 09.00 hours after an overnight fast) and then 60, 90
      (study 1 only) and 120 min post-dose. Both studies demonstrated that G115 alone
      significantly lowers fasting blood glucose levels. Conversely, in study 2 there
      was a significant drink x ginseng interaction suggesting opposing glycaemic
      effects of ginseng under fasting and raised blood glucose conditions. These data
      have implications for the use of ginseng in individuals with poor gluco
      regulation.

PMID- 17010222
TI  - Protective effects of tomato extract with elevated beta-carotene levels on
      oxidative stress in ARPE-19 cells.
AB  - Epidemiological studies show that dietary products rich in carotenoids delay the
      progression of age-related macular degeneration. Experimental evidence from
      cellular studies on the antioxidant actions of carotenoids in the retinal pigment
      epithelium is still, however, fragmentary. The present study examined the uptake
      and protective potential of dietary carotenoids from tomato on the human retinal
      pigment epithelial cell line ARPE-19. ARPE-19 cells were incubated in medium
      supplemented with tomato extract containing high levels of beta-carotene,
      lycopene and traces of lutein. The cellular uptake of carotenoids was analysed by
      reverse-phase HPLC. Oxidative stress was induced by treatment with 1 mm-H2O2.
      Nitrotyrosine was detected by immunocytochemistry, and oxidised proteins (protein
      carbonyls) were measured by a quantitative ELISA method. Lipid peroxidation was
      assessed by quantifying thiobarbituric acid reactive substances. ARPE-19 cells
      preferentially accumulated lutein and beta-carotene rather than lycopene.
      Nitrotyrosine formation was considerably reduced in cells incubated with tomato
      extract compared with controls after H2O2 treatment. Protein carbonyls were
      reduced by 30 % (P = 0.015), and the formation of thiobarbituric acid-reactive
      substances was reduced by 140 % (P = 0.003) in cells incubated with tomato
      extract. The present study provides the experimental evidence for protective
      effects of dietary tomatoes rich in carotenoids on oxidative stress in the
      retinal pigment epithelium.

PMID- 17010223
TI  - Effects of chronic cysteamine treatment on growth enhancement and insulin-like
      growth factor I and II mRNA levels in common carp tissues.
AB  - Insulin-like growth factors (IGF) belong to a family of growth factors with
      structural homology to proinsulin. In our previous studies, we found that both
      IGF-I and IGF-II gene expression showed growth hormone (GH) dependence in the
      brain and liver of juvenile common carp when treated in vivo with GH for a short
      time. This present work aimed to study the effects of both the short-term and
      long-term GH induction of IGF gene expression using cysteamine (CSH) and
      fasting/re-feeding. CSH is an agent that can deplete somatostatin to increase
      circulating GH level. IGF mRNA levels in the flesh (muscle) and liver of common
      carp were determined using real-time PCR. The chronic treatment of common carp
      with CSH was carried out for 63 d, with growth enhancement of the treated fish
      noted. Hepatic IGF-I and IGF-II mRNA levels increased in a dose-dependent manner
      with short-term CSH treatment, whereas IGF-I decreased and IGF-II increased in
      the liver after chronic CSH treatment. IGF-I and IGF-II mRNA levels in muscle
      were found to be elevated with the high-dose, long-term CSH treatment. Under the
      experimentally induced catabolic states of fasting, both hepatic IGF-I and IGF-II
      gene expression were significantly reduced, whereas they showed no change in
      muscle. After re-feeding, the hepatic expression of IGF-I in liver and muscle
      rebounded significantly. The hepatic IGF-II expression level showed no rebound
      after re-feeding, but the IGF-II level in muscle rebounded to the level of the
      fed group after re-feeding.

PMID- 17010224
TI  - Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in
      streptozotocin-induced diabetic rats.
AB  - In the present study, the hypoglycaemic potentials of ginger (Zingiber
      officinale) were studied in rats. An aqueous extract of raw ginger was
      administered daily (500 mg/kg, intraperitoneally) for a period of 7 weeks to
      streptozotocin (STZ)-induced diabetic rats. Fasting blood serum was analysed for
      blood glucose, cholesterol and triacylglycerol levels. The STZ-injected rats
      exhibited hyperglycaemia accompanied with weight loss, indicating their diabetic
      condition. At a dose of 500 mg/kg, raw ginger was significantly effective in
      lowering serum glucose, cholesterol and triacylglycerol levels in the ginger
      treated diabetic rats compared with the control diabetic rats. The ginger
      treatment also resulted in a significant reduction in urine protein levels. In
      addition, the ginger-treated diabetic rats sustained their initial weights during
      the treatment period. Moreover, ginger decreased both water intake and urine
      output in the STZ-induced diabetic rats. The present results indicate that raw
      ginger possesses hypoglycaemic, hypocholesterolaemic and hypolipidaemic
      potential. Additionally, raw ginger is effective in reversing the diabetic
      proteinuria observed in the diabetic rats. Thus, ginger may be of great value in
      managing the effects of diabetic complications in human subjects.

PMID- 17010225
TI  - Some metabolic effects on lactating rats of a low-energy diet restricted in good
      quality protein.
AB  - Adult female Sprague-Dawley rats were fed ad libitum during pregnancy and
      lactation a control diet (CD; 16.1 kJ/g) or a low-energy diet with wheat gluten
      as the main protein source (LED; 13.3 kJ/g). Body weight, food intake, resting
      energy expenditure, respiratory quotient and substrate use by the mammary gland
      were measured. After the animals had been killed, the parametrial and
      retroperitoneal fat pads were weighed. The mean food intake (g) of the two groups
      of rats was similar, resulting in a lower energy intake by the LED rats,
      significantly different during the last 2 weeks of lactation. The mean body
      weight of both dams and pups in the LED group was lower, starting at day 9 of
      lactation. The resting energy expenditure increased gradually during lactation in
      the control group, whereas this increase was not seen in rats of the LED group in
      the last week of lactation. Rats that had fasted overnight had a respiratory
      quotient of 0.7 or less, whereas for rats that had been fed, the mean respiratory
      quotient was over 1.0. Under both conditions, rats showed ketonuria. The
      arteriovenous difference in 3-hydroxybutyrate level was higher and those for
      glucose, lactate and triacylglycerol were lower across the mammary glands of LED
      rats. The parametrial fat depot weighed less in LED rats. Reducing the increase
      in resting energy expenditure and using ketone bodies to a greater extent as
      fuels may represent important mechanisms in the LED dams to cover the energy cost
      of milk production.

PMID- 17010226
TI  - Dietary fish protein alters blood lipid concentrations and hepatic genes involved
      in cholesterol homeostasis in the rat model.
AB  - It is known that various dietary plant proteins are capable of influencing the
      lipid metabolism of human subjects and animals when compared with casein. Less,
      however, is known about the effects of fish protein on the cholesterol and
      triacylglycerol metabolism. Therefore, two experiments were conducted in which
      rats were fed diets containing 200 g of either fish protein, prepared from Alaska
      pollack fillets, or casein, which served as control, per kilogram, over 20 and 22
      d, respectively. As parameters of lipid metabolism, the concentrations of
      cholesterol and triacylglycerols in the plasma and liver, the faecal excretion of
      bile acids and the hepatic expression of genes encoding proteins involved in
      lipid homeostasis were determined. In both experiments, rats fed fish protein had
      higher concentrations of cholesteryl esters in the liver, a lower concentration
      of cholesterol in the HDL fraction (rho > 1.063 kg/l) and lower plasma
      triacylglycerol concentrations than rats fed casein (P < 0.05). The gene
      expression analysis performed in experiment 2 showed that rats fed fish protein
      had higher relative mRNA concentrations of sterol regulatory element-binding
      protein (SREBP)-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase, LDL receptor,
      apo AI, scavenger receptor B1 and lecithin-cholesterol-acyltransferase in their
      liver than did rats fed casein (P < 0.05). The faecal excretion of bile acids and
      the mRNA concentrations of cholesterol 7alpha-hydroxylase, SREBP-1c and
      corresponding target genes were not altered. These findings show that fish
      protein had multiple effects on plasma and liver lipids that were at least in
      part caused by an altered expression of the hepatic genes involved in lipid
      homeostasis.

PMID- 17010227
TI  - Effect of nucleotide intake and nutritional recovery on insulin-like growth
      factor I and other hormonal biomarkers in severely malnourished children.
AB  - The objective of the present study is to demonstrate the effect of nucleotide
      intake and intensive nutritional support on the concentration of insulin-like
      growth factor I (IGF-I) and other hormonal biomarkers in severely malnourished
      children. Twenty-six severely malnourished children < 48 months of age received
      formula without lactose via enteral feeding for 2 weeks and ad libitum for an
      additional 2 weeks. Anthropometrical measurements were performed and serum
      concentrations of IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3),
      leptin, soluble leptin receptor (sOB-R), as well as the estimated molar excess of
      sOB-R over leptin were obtained. Two groups were formed. One group received
      formula with nucleotides (NT+; n 13) and the other without nucleotides (NT-; n
      13). A control group was included (n 13). Parametric and non-parametric tests as
      well as ANOVA models were used. Nutritional recovery, nucleotides intake, type of
      malnutrition, age and the interaction between gender and malnutrition influenced
      the concentration of IGF-I (P < 0.001). Nutritional recovery, nucleotides intake,
      gender and type of malnutrition had an effect on IGFBP-3 (P < 0.001). Nutritional
      recovery had a significant effect on serum leptin (P = 0.001). Age and
      nutritional recovery had an effect on sOB-R (P < 0.001); all variables included
      affected the molar excess of sOB-R over leptin (P < 0.001). In conclusion,
      nucleotide intake and nutritional recovery had a notable effect on IGF-I, IGFBP-3
      and other hormonal biomarkers. This outcome could stimulate the catch-up growth
      of severely malnourished infants and toddlers during the nutritional recovery
      period.

PMID- 17010228
TI  - Leptin directly regulates exocrine pancreas lipase and two related proteins in
      the rat.
AB  - Leptin, a metabolic regulator of energy expenditure, exerts its peripheral
      effects primarily by altering lipid metabolism. The exocrine pancreas has a key
      role in the digestion of dietary lipids, but the role of leptin in regulating
      pancreatic lipases remains unknown. Using the exocrine pancreas in vitro AR42J
      cell model, we studied the direct effects of leptin on pancreatic lipase (PL)
      secretion and on the mRNA levels of PL and PL-related proteins 1 and 2 (PLRP1,
      PLRP2). Leptin directly, rapidly (within 30 min) and significantly inhibited both
      the secretion and intracellular activity of PL. Leptin downregulated mRNA levels
      of PL and PLRP1, and upregulated transcripts of PLRP2. This study provides the
      first evidence that leptin directly regulates exocrine lipases at the levels of
      synthesis, activity and secretion. This rapid regulation may be associated with a
      short-term control of energy balance.

PMID- 17010229
TI  - Rumen ciliate protozoa contain high concentrations of conjugated linoleic acids
      and vaccenic acid, yet do not hydrogenate linoleic acid or desaturate stearic
      acid.
AB  - Conjugated linoleic acids (CLA) have been shown to improve human health. They are
      derived from the microbial conversion of dietary linoleic acid (cis-9,cis-12-18 :
      2 (LA)) in the rumen. An investigation was undertaken to determine the role of
      ruminal ciliate protozoa v. bacteria in the formation of CLA and its precursor in
      animal tissues, vaccenic acid (trans-11-18 : 1 (VA)). Mixed protozoa from the
      sheep rumen contained at least two to three times more unsaturated fatty acids,
      including CLA and VA, than bacteria. Different species had different composition,
      with larger fibrolytic species such as Epidinium ecaudatum caudatum containing
      more than ten times more CLA and VA than some small species, including Entodinium
      nanellum. In incubations with ruminal microbial fractions (bacterial fraction
      (BAC), protozoal fraction (PRO)), LA metabolism was very similar in strained
      ruminal fluid (SRF) and in the BAC, while the PRO had LA-metabolising activity an
      order of magnitude lower. Using PCR-based methods, no genes homologous to fatty
      acid desaturase genes were found in cDNA libraries from ruminal protozoa. The
      absence of an alternative route of VA/CLA formation via desaturation of stearate
      was confirmed by incubations of SRF, BAC or PRO with [14C]stearate. Thus,
      although protozoa are rich in CLA and VA, they appear to lack the ability to form
      these two fatty acids from LA or stearate. The most likely explanation is that
      protozoa preferentially incorporate CLA and VA formed by bacteria. The
      implication of the present findings is that the flow of unsaturated fatty acids,
      including CLA and VA, from the rumen could depend on the flow of protozoa rather
      than bacteria.

PMID- 17010230
TI  - Lactic acid fermentation stimulated iron absorption by Caco-2 cells is associated
      with increased soluble iron content in carrot juice.
AB  - An in vitro digestion/Caco-2 cell model was applied to explore the impact of
      lactic acid (LA) fermentation by Lactobacillus pentosus FSC1 and Leuconostoc
      mesenteroides FSC2 on the Fe bioavailability of carrot juice. The redox state of
      Fe in fermented carrot juice was also assessed as a crucial factor for
      absorption. LA fermentation was shown to improve mineral solubility to different
      extents at simulated physiological conditions: Mn (2-fold); Fe (1.5-1.7-fold); Zn
      (1.2-fold); Cu (1-fold). Soluble Fe2+ was increased about 16-fold by LA
      fermentation, and about one third of the Fe2+ remained soluble after in vitro
      digestion (about 4-5-fold higher than in fresh juice). Data on cell-line studies
      showed a 4-fold increase in the efficiency of Fe uptake, but not in
      transepithelial transfer by Caco2 cells, as a result of fermentation. The
      increases in Fe2+ level and the efficiency of cellular Fe uptake were strain
      dependent. To sum up the effect on both Fe solubility and cellular uptake
      efficiency, the amount of cellularly absorbed Fe from Ln. mesenteroides FSC2
      fermented juice was about 20 % higher than that from L. pentosus FSC1-fermented
      juice (22.7 v. 19.2 microg/l juice per mg protein). To conclude, LA fermentation
      enhanced Fe absorption by Caco-2 cells from carrot juice because of increases in
      not only Fe solubility after digestion, but also the efficiency of cellular Fe
      uptake. The fermentation-improved efficiency of Fe uptake was possibly due to the
      increased level of soluble Fe2+ rather than a being a strain-specific event.

PMID- 17010231
TI  - Changes in folate status in overweight/obese women following two different weight
      control programmes based on an increased consumption of vegetables or fortified
      breakfast cereals.
AB  - The modification of folate status was analysed in a group of sixty-seven
      overweight/obese women of childbearing age (20-35 years). Subjects were randomly
      assigned to one of two slightly hypocaloric diets: diet V (increased consumption
      of vegetables) or diet C (increased consumption of breakfast cereals). Dietetic,
      anthropometric and biochemical data were collected at the start of the study and
      again at 2 and 6 weeks. At 6 weeks a weight loss of 2.0 (sd 1.3) kg was achieved
      in V subjects and of 2.8 (sd 1.4) kg in C subjects (P < 0.05). At the start of
      the study, 64.2 % of all subjects had a folate intake of < 67 % of the
      recommended intake; this fell to just 3 % (7.14 % of V subjects and 0 % of C
      subjects) by week 6. Significant increases were only seen in C subjects in serum
      folate concentrations (both at 2 and 6 weeks), accompanied by a significant
      reduction in serum homocysteine (at week 6). Some 62.1 % of all subjects had
      serum folate concentrations of > or = 13.6 nmol/l (associated with a very low
      risk of neural tube defects) at the start of the study, while 87.0 % (85.2 % of V
      subjects and 88.9 % of C subjects) had concentrations of > or = 13.6 nmol/l at 6
      weeks (P < 0.01). Increasing the relative consumption of vegetables/cereals in
      the context of a slightly hypocaloric diet may therefore be a good way to lose
      body weight. Breakfast cereals may be of special help with respect to folate
      status and serum homocysteine levels in overweight/obese young women following
      energy restriction diets.

PMID- 17010232
TI  - Reference range of total serum homocysteine level and dietary indexes in healthy
      Greek schoolchildren aged 6-15 years.
AB  - Elevated total serum homocysteine (tHcy) may be a possible risk factor for CVD. A
      5 micromol/l increase in tHcy is associated with an approximately 70 % increase
      in relative risk of CVD in adults. Data for children and adolescents are,
      however, limited. The purpose of the present study was to provide a reference
      range for tHcy and investigate any relationship between tHcy and nutritional
      indexes in a Greek paediatric population. tHcy, folate, vitamin B12 levels and
      dietary indexes were measured in 520 healthy schoolchildren (274 boys, 246 girls)
      aged 6-15 years. As in adults, the tHcy distribution skewed to the right, with a
      geometric mean for both genders of 7.4 (range 3.4-29 micromol/l). Concentrations
      were lower in young children and increased with age. No statistically significant
      difference in tHcy level was observed between gender. The 95th percentiles for
      the three age groups were as follows: 6-9 years, 9.98 micromol/l; 10-12 years,
      10.62 micromol/l; 13-15 years, 14.4 micromol/l. Using Pearson's coefficient
      analysis, tHcy level was correlated with age, serum folate, BMI and systolic
      blood pressure. Dietary analysis showed that folate, vitamin B12 and fibre intake
      were inversely related with tHcy; conversely, sugar and fat were positively
      associated with tHcy. However, in multiple linear regression analysis, only age
      (odds ratio 0.246, P < 0.05) and folate (odds ratio -0.346, P < 0.05) were
      significantly and independently associated with tHcy. This study provides age
      specific reference data regarding tHcy concentration in a Greek paediatric
      population. tHcy levels increased as a function of age. Serum folate levels were
      significantly and independently associated with tHcy levels.

PMID- 17010233
TI  - Acute-phase protein levels, diarrhoea, Trichuris trichiura and maternal education
      are predictors of serum retinol: a cross-sectional study of children in a Dhaka
      slum, Bangladesh.
AB  - The objectives of the present study were to identify predictors of serum retinol
      concentration as well as to assess the prevalence of low serum retinol
      concentration, in both the whole population after correcting for the effect of
      serum C-reactive protein (CRP) (using multiple categories), and the healthy
      subgroup. A cross-sectional study of 579 apparently healthy children, aged 3-7
      years from a Dhaka slum, Bangladesh, was conducted. The effects of age, gender,
      serum CRP and alpha1-antichymotrypsin, reported morbidity (during the previous 2
      weeks), Ascaris lumbricoides and Trichuris trichiura infections, parental
      education, wasting, stunting and underweight on serum retinol were estimated
      using multiple linear regression. The mean serum retinol concentration was 0.84
      (sd 0.27) micromol/l. Elevated serum CRP levels, reported diarrhoea, reported
      nasal discharge and T. trichiura infection were negative predictors of serum
      retinol, whereas maternal education was a positive predictor. Compared with a
      serum CRP level of < 1 mg/l, CRP levels of 2 to < 5, 5 to < 10 and > or = 10 mg/l
      were associated with 0.12, 0.16 and 0.32 micromol/l lower serum retinol,
      respectively. The prevalence of low serum retinol (< 0.70 micromol/l) fell from
      31.2 % to 15.6 % in the whole population, after correcting for the effect of CRP,
      and was 20.1 % in the healthy subgroup (CRP < 2 mg/l). The prevalence of low
      serum retinol was high but overestimated due to the effect of CRP. Interventions
      are needed to address low serum retinol in Bangladesh. Controlling diarrhoea,
      nasal discharge and T. trichiura infection and improving maternal education may
      be important interventions. The use of multiple categories of acute-phase
      proteins and cut-off values that indicate elevated levels need further research.

PMID- 17010234
TI  - Longitudinal changes in dietary patterns during adult life.
AB  - Despite the growing interest in dietary patterns, there have been few
      longitudinal investigations. The objective of the present study was to extend an
      earlier method of dietary pattern assessment to longitudinal binary data and to
      assess changes in patterns over time and in relation to socio-demographic
      covariates. A prospective national cohort of 1265 participants completed a 5 d
      food diary at three time-points during their adult life (at age 36 years in 1982,
      43 years in 1989 and 53 years in 1999). Factor analysis identified three dietary
      patterns for women (fruit, vegetables and dairy; ethnic foods and alcohol; meat,
      potatoes and sweet foods) and two patterns in men (ethnic foods and alcohol;
      mixed). Trends in dietary pattern scores were calculated using random effects
      models. Marked changes were found in scores for all patterns between 1989 and
      1999, with only the meat, potatoes and sweet foods pattern in women recording a
      decline. In a multiple variable model that included the three time-points, socio
      demographic variables and BMI time-dependent covariates, both non-manual social
      class and higher education level were also strongly associated with the
      consumption of more items from the ethnic foods and alcohol pattern and the mixed
      pattern for men (P < 0.0001) and the fruit, vegetables and dairy pattern and the
      ethnic foods and alcohol pattern for women (P < 0.01). In conclusion,
      longitudinal changes in dietary patterns and across socio-economic groups can
      assist with targeting public health initiatives by identifying stages during
      adult life when interventions to improve diet would be most beneficial to health.

PMID- 17010235
TI  - Greater fruit and vegetable intake is associated with increased bone mass among
      postmenopausal Chinese women.
AB  - Although studies in Caucasian populations have reported the beneficial effects of
      intakes of fruit and vegetables on bone mass, limited data are available in the
      Asian populations. We examined the association of the intake of fruits and
      vegetables with bone mineral density (BMD) in a population-based cross-sectional
      study of 670 postmenopausal Chinese women aged 48-63 years. Habitual dietary
      intakes were assessed using a food frequency questionnaire. BMD at the whole
      body, lumbar spine and left hip were measured with dual-energy X-ray
      absorptiometry. Univariate regression analyses showed that the total intake of
      fruits and vegetables was significantly associated with greater BMD at the whole
      body, lumbar spine (L1-L4), total hip, trochanter and intertrochanter. An
      independently positive association between fruit and vegetable intake and BMD at
      the whole body (P = 0.005), lumbar spine (P < 0.001) and total hip (P = 0.024)
      remained even after adjusting for age, years since menopause, body weight and
      height, dietary energy, protein and Ca, and physical activities. A daily increase
      of 100 g fruit and vegetable intake was associated with 0.0062 (95 % CI 0.0019,
      0.0105) g/cm2, 0.0098 (95 % CI 0.0041, 0.0155) g/cm2 and 0.0060 (95 % CI 0.0011,
      0.0109) g/cm2 increases in BMD at the whole body, lumbar spine and total hip,
      respectively. In conclusion, greater fruit and vegetable intake is independently
      associated with better BMD among postmenopausal Chinese women.

PMID- 17010236
TI  - Effects of zinc supplementation on cognitive function in healthy middle-aged and
      older adults: the ZENITH study.
AB  - A randomised double-blind placebo-controlled design was employed to investigate
      the effects of Zn supplementation on cognitive function in 387 healthy adults
      aged 55-87 years. Several measures of visual memory, working memory, attention
      and reaction time were obtained using the Cambridge Automated Neuropsychological
      Test Battery at baseline and then after 3 and 6 months of 0 (placebo), 15 or 30
      mg Zn/d. Younger adults (< 70 years) performed significantly better on all tests
      than older adults (> 70 years), and performance improved with practice on some
      measures. For two out of eight dependent variables, there were significant
      interactions indicating a beneficial effect (at 3 months only) of both 15 and 30
      mg/d on one measure of spatial working memory and a detrimental effect of 15 mg/d
      on one measure of attention. Further work is required to establish whether these
      findings generalise to older adults in poorer mental and physical health and with
      less adequate Zn intake and status than the present sample.

PMID- 17010237
TI  - Effects of distraction on the development of satiety.
AB  - Two experiments explored the hypothesis that distraction causes a reduced
      sensitivity to the physiological and sensory cues that signal when to terminate a
      meal. In Experiment 1, eighty-eight females ate five 'Jaffa Cakes' either while
      distracted by a computer game or while sitting in silence. Analysis of the
      difference in rated hunger, fullness and desire to eat (pre- to post-intake)
      revealed that distracted participants experienced smaller changes in their desire
      to eat and fullness than did non-distracted participants. Experiment 2 assessed
      whether changes in ratings are attenuated because sensory-specific satiety (or a
      related process) fails to develop. Using a similar procedure, eighty-four females
      provided desire to eat, pleasantness and intensity ratings for Jaffa Cakes and
      for two 'uneaten' foods, both before and at three time-points after consuming
      five Jaffa Cakes. Non-distracted participants reported a reduction in their
      desire to eat the eaten food relative to the uneaten food (food-specific
      satiety), whereas distracted participants maintained a desire to eat all foods.
      Moreover, this difference between distracted and non-distracted participants was
      evident 5 and 10 min after the eating episode had terminated. The present
      findings invite speculation that distraction attenuates the development of
      sensory-specific satiety, and that this effect persists (at least for a brief
      period) after the distractor has terminated. More generally, this kind of
      phenomenon warrants further scrutiny because it holds the potential to contribute
      towards overeating, either by prolonging an eating episode or by reducing the
      interval between meals.

PMID- 17010238
TI  - Risk of iron overload in carriers of genetic mutations associated with hereditary
      haemochromatosis: UK Food Standards Agency workshop.
AB  - The UK Food Standards Agency convened a group of expert scientists to review
      current research investigating diet and carriers of genetic mutations associated
      with hereditary haemochromatosis. The workshop concluded that individuals who are
      heterozygous for the C282Y mutation of the HFE gene do not appear to respond
      abnormally to dietary Fe and therefore do not need to change their diet to
      prevent accumulation of body Fe.

PMID- 17010239
TI  - Early nutrition and immunity - progress and perspectives.
AB  - The immune system exists to protect the host against pathogenic organisms and
      highly complex pathways of recognition, response, elimination and memory have
      evolved in order to fulfil this role. The immune system also acts to ensure
      tolerance to 'self', to food and other environmental components, and to commensal
      bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory
      diseases. The prevalence of inflammatory diseases, including atopic disorders,
      has increased over the last 60 years. The development of tolerance is the result
      of active immune mechanisms and both development and maintenance of tolerance are
      lifelong processes which start very early in life, even prenatally. Profound
      immunologic changes occur during pregnancy, involving a polarization of T helper
      (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in
      both mother and fetus. This situation is important to maintain pregnancy through
      avoidance of the rejection of the immunologically incompatible fetus. During the
      third trimester of human pregnancy, fetal T cells are able to mount antigen
      specific responses to environmental and food-derived antigens and antigen
      specific T cells are detectable in cord blood in virtually all newborns
      indicating in utero sensitization. If the neonatal immune system is not able to
      down-regulate the pre-existing Th2 dominance effectively then an allergic
      phenotype may develop. Changes occur at, and soon after, birth in order that the
      immune system of the neonate becomes competent and functional and that the gut
      becomes colonized with bacteria. Exposure to bacteria during birth and from the
      mother's skin and the provision of immunologic factors in breast milk are amongst
      the key events that promote maturation of the infant's gut and gut-associated and
      systemic immune systems. The introduction of formula and of solid foods exposes
      the infant to novel food antigens and also affects the gut flora. Nutrition may
      be the source of antigens to which the immune system must become tolerant,
      provide factors, including nutrients, that themselves might modulate immune
      maturation and responses, and provide factors that influence intestinal flora,
      which in turn will affect antigen exposure, immune maturation and immune
      responses. Through these mechanisms it is possible that nutrition early in life
      might affect later immune competence, the ability to mount an appropriate immune
      response upon infection, the ability to develop a tolerogenic response to 'self'
      and to benign environmental antigens, and the development of immunologic
      disorders. A Workshop held in February 2006 considered recent findings in the
      areas of oral tolerance, routes of sensitization to allergens and factors
      affecting the development of atopic disease; factors influencing the maturation
      of dendritic cells and the development of regulatory T cells; the influence of
      gut microflora on immunity, allergic sensitization and infectious disease; the
      role of nutrition in preventing necrotizing enterocolitis in an animal model of
      preterm birth; and the role of PUFA of different classes in influencing immune
      responses and in shaping the development of atopic disease. This report
      summarizes the content of the lectures and the subsequent discussions.

PMID- 17010240
TI  - Serum phytosterols not only from dietary intake.

PMID- 17010243
TI  - Gene-environment interactions and public health nutrition.

PMID- 17010244
TI  - Out of the box.

PMID- 17010245
TI  - Mandatory folic acid fortification and the science of 'sociality'.

PMID- 17010247
TI  - Poverty and household food security of black South African farm workers: the
      legacy of social inequalities.
AB  - OBJECTIVE: To assess socio-economic indicators, nutritional status and living
      conditions of farm workers and their families, with the purpose to develop
      research and intervention programmes aimed at enhancing nutritional status and
      quality of life. DESIGN AND SETTING: Three farm schools in two districts of the
      North-West Province and farming communities were selected. Anthropometrical
      measurements, structured face-to-face questionnaires and focus group discussions
      were carried out in 2002 and 2003 by a multidisciplinary research team. RESULTS:
      Access to electricity, water and sanitation, as well as monthly food rations or
      subsidies, vary and depend on farm owners. The majority of adults have education
      below or up to grade four, farm schools provide only up to grade seven. Distance
      to farm schools and intra-household issues hamper children's attendance and
      performance at school. Household food security is compromised due to a lack of
      financial resources, infrastructure and also household resource allocation. This
      impacts negatively especially on children, with half of them being underweight,
      stunted or wasted. Employment is usually linked to men, while most women have
      access to casual jobs only. Insecurity of residence and the perceived
      disempowered position towards farm owners add to feelings of hopelessness and
      stress. CONCLUSIONS AND RECOMMENDATIONS: This study highlights destitute living
      conditions of farm worker families. Apart from structural and financial
      constraints, paternalistic structures of the past might also hamper development.
      Based on these findings, follow-up research projects and in-depth investigations
      into underlying social issues with regard to nutrition insecurity and livelihoods
      of farm workers were initiated.

PMID- 17010248
TI  - A comparison of the availability and affordability of a market basket in two
      communities in the Chicago area.
AB  - OBJECTIVE: The purpose of the present study was to characterise the food
      landscape of an inner city African American neighbourhood and its mixed-race
      suburban neighbour. Detailed analysis focuses on the relationship between
      community store mix and price, availability and produce quality. DESIGN: A market
      basket study was completed by members of the Chicago Food Systems Collaborative.
      The US Department of Agriculture's standard market basket survey and methodology
      were used. Additional items and analyses were added in consultation with
      community members. SETTING: Austin is a lower-middle-class African American
      community of 117,500 on the western edge of Chicago. Oak Park, which borders
      Austin, is an upper-middle-income suburb of 52,500 with a mixed racial profile.
      SUBJECTS: A market basket survey of every retail food store in Austin and Oak
      Park was completed. A total of 134 were included. RESULTS: Results indicate that
      Austin has many grocery stores and few supermarkets. Many Austin groceries stores
      carry produce that is usually competitively priced, but often of unacceptable
      quality. Supermarkets had the best selection. Prices were lowest at discount
      supermarkets. Prices of packaged items were higher at independent stores than at
      chain supermarkets, but fresh items were cheaper. CONCLUSIONS: Food access is
      related more to store type than number. In this study, item availability and
      produce quality varied greatly between store types. Price differences were
      complicated and varied by store type and food category. This has consequences in
      terms of food purchasing decisions and dietary quality that public health
      professionals should acknowledge.

PMID- 17010249
TI  - Are green caterers more likely to serve healthy meals than non-green caterers?
      Results from a quantitative study in Danish worksite catering.
AB  - OBJECTIVE: The present study aimed to investigate whether organic conversion in
      catering has positive effects on the nutritional quality of menus offered.
      DESIGN: The methodology was based on a self-administered questionnaire. The self
      declared priority given to the use of organic foods was measured as the basis for
      assigning catering managers to one of two groups: 'green' or 'non-green'
      caterers. These groups were then compared with regard to the relative nutritional
      quality of the menu options offered to customers. SETTING: The study was carried
      out among randomly selected Danish worksite catering outlets. SUBJECTS: The
      subjects participating in the study comprised 526 Danish worksite catering
      managers. RESULTS: The results showed a strong correlation between caterers'
      'green-ness' and the nutritional quality of the menu options offered. Green
      caters had more healthy options in their menus than non-green caters, which is
      likely to result in improved nutritional quality of the diets of end consumers.
      The reason for this may partly be the increased service training efforts that
      green caterers practise in order to be able to implement organic foods
      successfully. It may also be associated with the fact that the price premiums and
      availability of the organic products forces caterers to serve menus with higher
      amounts of root and non-green leafy vegetables, pulses and seasonal vegetables.
      CONCLUSION: The present findings suggest that organic conversion of public
      canteens may be a good opportunity to promote healthier eating in public
      catering.

PMID- 17010250
TI  - Physical activity, diet and gene-environment interactions in relation to body
      mass index and waist circumference: the Swedish young male twins study.
AB  - OBJECTIVE: The aim of the present study was to examine the relationships between
      genetic susceptibility to obesity, physical activity (PA), dietary fibre, sugar
      and fat intakes and 4-year changes in body mass index (BMI) and attained waist
      circumference (WC) in a cohort of 287 monozygotic and 189 dizygotic young adult
      male twin pairs. Increased knowledge about interactions between genes and
      environment may provide insight into why some individuals are more prone to
      obesity than others. DESIGN: Information about PA, BMI, dietary habits, WC and
      potential confounders was collected by questionnaire in 1998 and 2002. The cohort
      data were analysed by mixed linear models. RESULTS: Twins with low PA attained
      larger WC than twins with high PA (difference 2.5 cm; 95% confidence interval
      (CI) 1.3, 3.6). The twins with the lowest fibre intake were found to have
      attained the highest WC and to have increased most in BMI (difference between
      highest and lowest fibre intakes: 1.6 cm, 95% CI 0.4, 2.9 and 0.45 kg m(-2), 95%
      CI 0.15, 0.76, respectively). Furthermore, our results suggested the presence of
      interactions so that twins with genetic susceptibility to obesity were more prone
      to have larger WC if sedentary than twins without genetic susceptibility.
      CONCLUSION: PA and a diet rich in fibre may be protective against weight gain
      among younger adult men. An interaction between PA, genes and attained WC is a
      novel finding which needs confirmation by other studies.

PMID- 17010251
TI  - Apolipoprotein E polymorphism and changes in serum lipids during a family-based
      counselling intervention.
AB  - OBJECTIVE: To compare serum lipids and their changes during a family-based health
      education in children aged 6-17 years with or without the epsilon4 allele of the
      gene encoding apolipoprotein E (apoE). DESIGN: An intervention study. SETTING: A
      family-based prevention of risk factors of coronary heart disease in Eastern
      Finland. The programme consisted of two counselling meetings at children's
      schools and three at children's homes. SUBJECTS: Four hundred and thirty-nine
      children with a family history of cardiovascular diseases (CVD) participated in a
      family-based health education. The children were divided into two groups
      according to apoE genotype. The risk group consisted of 143 children having apoE
      epsilon4 allele (genotype epsilon3/4 or epsilon4/4) and the non-risk group of 296
      children without apoE epsilon4 allele (epsilon2/3 or epsilon3/3). The final
      sample of the follow-up study included 354 (81%) children (114 and 240,
      respectively). RESULTS: Baseline differences were found in low-density
      lipoprotein cholesterol (LDL-C) (P=0.007) and LDL-C/high-density lipoprotein
      cholesterol (HDL-C) ratio (P=0.030) among boys and in total cholesterol (TC)/HDL
      C (P=0.008) and LDL-C/HDL-C ratios (P=0.006) among girls. Differences between
      groups in changes during the follow-up were observed only for TC/HDL-C ratio (P
      value adjusted for age=0.049) among boys. CONCLUSIONS: At baseline, children with
      apoE epsilon4 allele had on average a more unfavourable lipid profile than those
      without apoE epsilon4 allele. However, the effect of about 33 months' family
      based health education on plasma lipids did not depend on apoE genotype in
      children with a family history of CVD.

PMID- 17010252
TI  - Participants' willingness to consume soy foods for lowering cholesterol and
      receive counselling on cardiovascular disease by nutrition professionals.
AB  - OBJECTIVES: To determine if participants would be interested in consuming soy
      foods to lower cholesterol in primary and secondary prevention of heart disease,
      and to identify the role physicians and registered dietitians have in providing
      dietary advice, about soy foods or other foods, for participants with elevated
      cholesterol. METHODOLOGY: Qualitative data from 12 focus groups were gathered
      from a convenience sample of 74 adults, aged 18-91 years, with and without high
      cholesterol (total cholesterol >200 mg dl(-1)). Participants were recruited from
      Minneapolis/St. Paul mainstream and natural foods grocery stores. Focus group
      interviews were taped and transcribed verbatim. Common themes were identified,
      coded and compared using NVivo computer software. RESULTS: Participants believed
      diet, lifestyle and genetics were the cause of high cholesterol and
      cardiovascular disease (CVD). Few participants were aware of the Food and Drug
      Administration health claim for soy protein, yet many were willing to consume soy
      as part of lifestyle modification to prevent CVD. They reported preferring food
      and exercise over medication to treat high cholesterol. Few participants had ever
      received dietary advice from physicians on treating high cholesterol or CVD, and
      most doubted the accuracy of such advice. They believed registered dietitians
      were the most credible source of nutrition counselling and expressed an interest
      in physician referrals to dietitians. CONCLUSIONS: A collaboration and referral
      system between physicians and registered dietitians could increase CVD patients'
      consumption of soy foods as a means potentially leading to a reduced risk of
      heart disease in participants.

PMID- 17010253
TI  - Alcohol and dietary fibre intakes affect circulating sex hormones among
      premenopausal women.
AB  - BACKGROUND: The association of alcohol and fibre intake with breast cancer may be
      mediated by circulating sex hormone levels, which are predictors of breast cancer
      risk. OBJECTIVE: To evaluate the relationship of alcohol and dietary fibre intake
      with circulating sex hormone levels among premenopausal women. METHODS: A total
      of 205 premenopausal women completed a validated food-frequency questionnaire at
      baseline and after 2 years; blood samples taken at the same time were analysed
      for circulating sex hormone concentrations, including oestrone (E1), oestradiol
      (E2), free E2, progesterone, androstenedione and sex hormone-binding globulin, by
      radioimmunoassay. We used mixed models to estimate least-square means of sex
      hormone concentrations for alcohol intake categories and quartiles of dietary
      intake. RESULTS: After adjustment for covariates, alcohol consumption was
      moderately associated with higher circulating oestrogen levels; those who
      consumed more than one drink per day had 20% higher E2 (Ptrend=0.07) levels than
      non-drinkers. In contrast, higher dietary fibre intake was associated with lower
      serum levels of androstenedione (-8% between the lowest and highest quartiles of
      intake, Ptrend=0.06), but not oestrogens. Similarly, consumption of fruits (-12%,
      Ptrend=0.03), vegetables (-9%, Ptrend=0.15) and whole grains (-7%, Ptrend=0.07)
      showed inverse associations with androstenedione levels. CONCLUSIONS: The
      consistency of the observed differences in sex hormone levels associated with
      alcohol and fibre-rich foods indicates that these nutritional factors may affect
      sex hormone concentrations and play a role in breast cancer aetiology and
      prevention.

PMID- 17010254
TI  - Habitual fish consumption and risk of incident stroke: the European Prospective
      Investigation into Cancer (EPIC)-Norfolk prospective population study.
AB  - OBJECTIVES: To examine the association between fish consumption and stroke risk.
      DESIGN: Prospective population cohort study. SETTING: Norfolk, UK cohort of the
      European Prospective Investigation into Cancer (EPIC-Norfolk). SUBJECTS: Subjects
      were 24 312 men and women aged 40-79 years who had no previous history of stroke
      at baseline. METHODS: Fish consumption was assessed using a food-frequency
      questionnaire at baseline in 1993-1997 and stroke incidence ascertained to 2004.
      RESULTS: A total of 421 incident strokes were identified (mean follow-up=8.5
      years, total person-years=209 238). There were no significant relationships
      between total fish, shellfish or fish roe consumption and risk of stroke in men
      and women after adjusting for age, systolic blood pressure, body mass index,
      smoking, cholesterol, diabetes, physical activity, alcohol consumption, fish oil
      supplement use and total energy intake using Cox regression analyses. Oily fish
      consumption was significantly lower in women who subsequently had a stroke (odds
      ratio (OR) for consumers vs. non-consumers=0.69, 95% confidence interval (CI)
      0.51-0.94, P=0.02). The trend in men was similar but not significant (OR for
      consumers vs. non-consumers=0.88, 95% CI 0.65-1.19, P=0.41). CONCLUSIONS: There
      was no consistent relationship between fish consumption and stroke in this
      British population. Inconsistencies in the observed health effects of fish
      consumption in different populations may reflect different patterns and type of
      fish consumed and preparation methods.

PMID- 17010255
TI  - Parental concerns about childhood obesity and the strategies employed to prevent
      unhealthy weight gain in children.
AB  - OBJECTIVES: To describe parental concerns about their child's weight, to
      determine the proportion of parents taking preventive action to avoid obesity in
      their children and the predictors of taking preventive action, and to describe
      the strategies adopted by parents. DESIGN: A cross-sectional survey was
      conducted. Children's heights and weights were measured, and parents completed a
      questionnaire that included measures of their own weight status, perceptions of
      their child's weight, concerns about their child's current weight and future
      weight as an adolescent and adult, and the strategies used to prevent obesity.
      SETTING: The study was conducted in Melbourne, Australia. SUBJECTS: A total of
      291 families of children aged 5-6 years and 919 families of children aged 10-12
      years participated. RESULTS: Eighty-nine per cent of parents of overweight 5-6
      year-olds and 63% of parents of overweight 10-12-year-olds were unaware their
      child was overweight. Seventy-one per cent of parents of overweight 5-6-year-olds
      and 43% of parents of overweight 10-12-year-olds were not concerned about their
      child's current weight. Although 31% of parents of 5-6-year-olds and 43% of
      parents of 10-12-year-olds were taking action to prevent unhealthy weight gain in
      their children, less-educated parents were less likely to do so. CONCLUSIONS:
      Public health programmes are required to raise parental recognition of childhood
      overweight and of related risk behaviours, and to provide parents with practical
      strategies to prevent unhealthy weight gain in their children.

PMID- 17010256
TI  - Anthropometry and body composition of south Indian babies at birth.
AB  - OBJECTIVES: To assess the consequences on body composition of increasing birth
      weight in Indian babies in relation to reported values in Western babies, and to
      assess the relationship between maternal and neonatal anthropometry and body
      composition. DESIGN: Prospective observational study. SETTING: Bangalore City,
      India. SUBJECTS: A total of 712 women were recruited at 12.5+/-3.1 weeks of
      gestation (mean+/-standard deviation, SD) and followed up until delivery; 14.5%
      were lost to follow-up. Maternal body weight, height, mid upper-arm circumference
      and skinfold thicknesses were measured at recruitment. Weight and body
      composition of the baby (skinfold thicknesses, mid upper-arm circumference,
      derived arm fat index and arm muscle index; AFI and AMI, respectively) were
      measured at birth in hospital. RESULTS: The mean+/-SD birth weight of all
      newborns was 2.80+/-0.44 kg. Birth weight was significantly related to the
      triceps and subscapular skinfold thickness of the baby. In a small number of
      babies with large birth weight for gestational age, there was a relatively higher
      normalised AFI relative to AMI than for babies with lower or appropriate birth
      weight for gestational age. Maternal height and fat-free mass were significantly
      associated with the baby's length at birth. CONCLUSIONS: Skinfold thicknesses in
      Indian babies were similar to those reported in a Western population with
      comparable birth weights, and the relationship of AFI to birth weight appeared to
      be steeper in Indian babies. Thus, measures to increase birth weight in Indian
      babies should take into account possible adverse consequences on body
      composition. There were no significant relationships between maternal
      anthropometry and body composition at birth on multivariate analysis, except for
      sum of the baby's skinfold thicknesses and maternal fat-free mass (P<0.02).

PMID- 17010257
TI  - Effect of iron supplementation on physical growth in children: systematic review
      of randomised controlled trials.
AB  - OBJECTIVE: To evaluate the effect of iron supplementation on physical growth in
      children through a systematic review of randomised controlled trials (RCTs). DATA
      SOURCES: Electronic databases, personal files, and hand search of reviews,
      bibliographies of books, abstracts and proceedings of international conferences.
      REVIEW METHODS: RCTs evaluating change in anthropometry with interventions that
      included oral or parenteral iron supplementation, or iron-fortified formula milk
      or cereals, were analysed. RESULTS: Twenty-five trials (26 cohorts) had relevant
      information. There was no evidence of publication bias. The pooled estimates
      (random effects model) did not document a statistically significant (P>0.05)
      positive effect of iron supplementation on any anthropometric variable (weight
      for-age, weight-for-height, height-for-age, mid upper-arm circumference, skinfold
      thickness, head circumference). Significant heterogeneity was evident, and its
      predictors included greater weight-for-age in supplemented children in malaria
      hyperendemic regions and greater weight-for-height for children above 5 years of
      age, but a negative effect on linear growth in developed countries and with
      supplementation for 6 months or longer. CONCLUSIONS: This review did not document
      a positive effect of iron supplementation on the physical growth of children. The
      identified predictors of heterogeneity should be considered as exploratory and
      requiring confirmation, not conclusive.

PMID- 17010258
TI  - Folate deficiency is associated with nutritional anaemia in Lebanese women of
      childbearing age.
AB  - OBJECTIVE: The objective of this study was to identify the determinants of
      anaemia in Lebanese women of childbearing age attending health centres in
      Lebanon. DESIGN: Cross-sectional study carried out between May and December 2003.
      Anthropometric measurements as well as sociodemographic, health and dietary
      intake data were collected using a questionnaire. Haemoglobin (Hb), plasma
      ferritin, plasma folate and vitamin B12 were assessed using standard laboratory
      methods. SETTING: Governmental health centres in Lebanon. SUBJECTS: Four hundred
      and seventy non-pregnant Lebanese women aged 15-45 years. RESULTS: Anaemia (Hb
      <12 g dl(-1)) and iron deficiency (ferritin <15 microg l(-1)) were prevalent in
      16.0 and 27.2% of the study sample, respectively. Of the total sample, 7.7% had
      iron-deficiency anaemia. The percentage of women with either Hb or ferritin
      deficiency or both was 35.6%. Plasma folate and vitamin B12 deficiency was
      reported in 25.1 and 39.4%, respectively, and 12.6% of the women had both folate
      and vitamin B12 deficiencies. Of the anaemic group, 48.0% of the women had iron
      deficiency. The intake of iron was lower in iron-deficient than in non-deficient
      women and a positive relationship was shown between folate intake and its
      corresponding serum levels. Regression analysis showed that ferritin, plasma
      folate and family history of anaemia were significant determinants of the anaemia
      in the sample of women. CONCLUSIONS: Anaemia not related to iron deficiency was
      partly explained by plasma folate deficiency. Measures to control folate and iron
      deficiency should be considered.

PMID- 17010259
TI  - Validity of a food-frequency questionnaire for elderly men in southeast China.
AB  - OBJECTIVE: To investigate the internal validity of a food-frequency questionnaire
      (FFQ) developed for a case-control study of prostate cancer in southeast China.
      DESIGN: A comprehensive questionnaire comprising a quantitative FFQ and a short
      food habit questionnaire (SFHQ) was developed and modified from previous cancer
      and nutritional studies. The Goldberg formula (ratio of energy intake (EI) to
      basal metabolic rate (BMR), EI/BMR) was used to assess the validity of the FFQ by
      making comparisons with physical activity levels. Physical activity levels were
      measured by the estimated total metabolic equivalents (MET) and the ratio of
      energy expenditure (EE) to BMR (EE/BMR). Correlation analyses were undertaken to
      compare the SFHQ variables with those of the quantitative FFQ. SETTING: Hangzhou,
      Zhejiang Province, China. SUBJECTS: A total of 404 men over 45 years old with or
      without prostate cancer were recruited from eight hospitals. RESULTS: The partial
      correlation coefficients, controlling for age and family history of prostate
      cancer, were moderate to high (P<0.05) for preserved foods intake, fat
      consumption and tea drinking variables between the SFHQ and the quantitative FFQ.
      The average EI/BMR was 1.72, with 76% of subjects exceeding the Goldberg cut-off
      value of 1.35. Apart from weight, BMI, EE/BMR and MET, there were no significant
      differences in characteristics between low (<1.35) and normal EI/BMR groups.
      CONCLUSIONS: The FFQ is demonstrated to be a valid instrument to measure energy
      and food intake for elderly men in southeast China.

PMID- 17010260
TI  - Validation of an estimated food record.
AB  - OBJECTIVE: To validate an estimated food record (EFR), using a weighed food
      record (WFR) as the reference method, for the determination of food consumption
      and nutrient intakes in a group of Costa Rican adults. DESIGN: For the WFR, all
      foods consumed by subjects during seven consecutive days were weighed and
      recorded by nutrition students. Two EFRs (a 4-day and a 3-day record) were
      recorded by subjects with the use of home measures and photographs to estimate
      amounts. SETTING: Costa Rica. SUBJECTS: Sixty adults: 30 men and 30 women; 30
      living in urban and 30 in rural areas. RESULTS: The EFR gave statistically
      significant lower average intake estimates for energy and 12 of the 22 nutrients
      examined. The correlation coefficients ranged from 0.68 (polyunsaturated fats) to
      0.87 (calcium). The percentage of subjects classified into the same quartile
      ranged from 45.0% (polyunsaturated fats) to 68.3% (vitamin B12). For all
      nutrients except vitamin C, 0 or 1.7% were misclassified into extreme quartiles.
      For food group consumption, the EFR gave statistically significant lower
      estimates for six of the 17 groups and correlation coefficients ranged from 0.22
      (fish) to 0.93 (beverages). Greater differences in estimates of mean energy and
      nutrient intakes were detected among subjects from rural areas, caused in part by
      a tendency to underestimate the amounts of rice and beans consumed. CONCLUSION:
      Validation of the EFR using a WFR as the reference method gave results that
      compare favourably with those reported by other authors, and support the use of
      the EFR for dietary surveys among Costa Rican adults.

PMID- 17010261
TI  - Comparison of the World Health Organization (WHO) Child Growth Standards and the
      National Center for Health Statistics/WHO international growth reference:
      implications for child health programmes.
AB  - OBJECTIVES: To compare growth patterns and estimates of malnutrition based on the
      World Health Organization (WHO) Child Growth Standards ('the WHO standards') and
      the National Center for Health Statistics (NCHS)/WHO international growth
      reference ('the NCHS reference'), and discuss implications for child health
      programmes. DESIGN: Secondary analysis of longitudinal data to compare growth
      patterns (birth to 12 months) and data from two cross-sectional surveys to
      compare estimates of malnutrition among under-fives. SETTINGS: Bangladesh,
      Dominican Republic and a pooled sample of infants from North America and Northern
      Europe. SUBJECTS: Respectively 4787, 10 381 and 226 infants and children.
      RESULTS: Healthy breast-fed infants tracked along the WHO standard's weight-for
      age mean Z-score while appearing to falter on the NCHS reference from 2 months
      onwards. Underweight rates increased during the first six months and thereafter
      decreased when based on the WHO standards. For all age groups stunting rates were
      higher according to the WHO standards. Wasting and severe wasting were
      substantially higher during the first half of infancy. Thereafter, the prevalence
      of severe wasting continued to be 1.5 to 2.5 times that of the NCHS reference.
      The increase in overweight rates based on the WHO standards varied by age group,
      with an overall relative increase of 34%. CONCLUSIONS: The WHO standards provide
      a better tool to monitor the rapid and changing rate of growth in early infancy.
      Their adoption will have important implications for child health with respect to
      the assessment of lactation performance and the adequacy of infant feeding.
      Population estimates of malnutrition will vary by age, growth indicator and the
      nutritional status of index populations.

PMID- 17010262
TI  - Serum levels of total immunoglobulin e in patients with alopecia areata:
      relationship with clinical type of the disease.
AB  - Alopecia areata (AA) is a heterogeneous disease characterized by nonscarring hair
      loss on the scalp or any hair-bearing surface. A wide range of clinical
      presentations can occur, from a single patch of hair loss to complete loss of
      hair on the scalp (alopecia totalis, AT) or over the entire body (alopecia
      universalis, AU). The cause of AA is unknown although most evidence supports the
      hypothesis that AA is an immunologically mediated disease. The aim of the study
      was to compare serum levels of total immunoglobulin E (IgE) between patients with
      AA and healthy subjects, and to assess the difference between the localized form
      and extensive forms of the disease such as AT and AU. Sixty patients with AA and
      50 healthy subjects were enrolled in the study. Fifty patients had localized AA
      (LAA), and ten patients had AT, AU or AT/AU. Serum levels of IgE were measured
      using fluoroenzyme immunoassay techniques. Serum levels of total IgE were
      significantly higher in AA patients than in controls (p<0.05). There was no
      significant difference in serum levels of total IgE between patients with LAA and
      those with extensive forms of the disease (p>0.05). The exact role of serum IgE
      in AA should be additionally investigated in future studies.

PMID- 17010263
TI  - Airborne dermatosis.
AB  - Dermatologists and occupational physicians are those who have to deal with
      airborne allergens and irritants most often, and the awareness of these
      substances has grown over the years. In this report, skin symptoms of airborne
      dermatosis, the nature of airborne contactans, and the localization of lesions
      are presented, along with the differential diagnoses. Recognizing the
      characteristic nature of these reactions can greatly facilitate the diagnosis.

PMID- 17010264
TI  - Epicutaneous patch test results in patients with allergic contact dermatitis in
      Karlovac county--a retrospective survey.
AB  - During the 1994-2003 study period, patch testing was carried out in 1102 subjects
      (740 female and 362 male, mean age 39.8, range 7-81 years) suspected to have
      allergic contact dermatitis (ACD). Epicutaneous patch test with a standard series
      of contact allergens was made by the Institute of Immunology, Zagreb, Croatia,
      according to the Internationational Contact Dermatitis Research Group (ICDRG)
      rules. During the study period, 399 (36.2%) subjects with one or more positive
      tests were recorded, and 640 positive tests were observed. The most frequent
      allergens were nickel sulfate identified in 214 (33.4%), cobalt chloride in 64
      (10%), fragrance mix in 60 (9.4%), wood tar in 47 (7.3%), potassium dichromate in
      39 (6.1%), balsam of Peru in 29 (4.6%) and other allergens in 187 (29.2%) cases.
      According to the localization of ACD, hands as the most common site were involved
      in 535 (48.5%) cases, followed by the face in 167 (15.2%) and other locations in
      400 (36.3%) cases. It is concluded that nickel is the principal allergen as the
      cause of ACD, mostly affecting women. The areas most frequently involved by ACD
      were the hands and face.

PMID- 17010265
TI  - Contact dermatitis to temporary tattoo.
AB  - The development of contact hypersensitivity to temporary tattoos has been on an
      increase all over the world. Skin painting with henna is a traditional practice
      in the Moslems and Hindu, and has recently been increasingly used in western
      countries. Black henna is obtained by adding paraphenylenediamine to the natural
      occurring henna. The risk of sensitization increases with the length of contact
      and increase of the concentration. A case is presented of an 11-year-old boy who
      developed a severe reaction in the form of redness and edema accompanied by
      pruritus on the day following the application of a temporary tattoo. A year
      before, the patient had also developed a skin reaction following temporary
      tattooing, which had not been recognized as a contact dermatitis. Patch testing
      was positive for paraphenylenediamine and thiuram compounds. The patient was
      treated with medium-strength corticosteroids.

PMID- 17010266
TI  - Gloves and socks syndrome associated with parvovirus B19 infection.
AB  - The spectrum of disease caused by parvovirus B19 infection ranges from
      asymptomatic to a serious disease. Parvovirus B19 plays a role in the
      pathomechanism of gloves and socks syndrome, erythema infectiosum, acute
      polyarthralgia, aplastic crisis in persons with hemolytic anemia, and birth
      defects. Gloves and socks syndrome has an acute febrile course. Painful edema of
      hands and feet, and numerous small confluent petechiae in the same localization
      are the most characteristic signs. Blisters and erosions may occur in oral
      mucosa. General discomfort and arthralgia accompany skin lesions. The disease
      tends to be self-limiting. A typical case of gloves and socks syndrome in a 36
      year-old woman is reported. Serological tests disclosed the parvovirus B19
      infection, confirming the causal relationship between the syndrome and this
      infection.

PMID- 17010267
TI  - Neurofibromatosis--review of the literature and case report.
AB  - Neurofibromatoses are genetic disorders of the nervous system that primarily
      affect the development and growth of neural (nerve) cell tissues. These disorders
      cause tumors to grow on nerves, and produce other abnormalities such as skin
      changes and bone deformities. Although many affected persons inherit the
      disorder, between 30 and 50 percent of new cases arise spontaneously through
      mutation in the individual's genes. We report on seven cases of type 1
      neurofibromatosis (NF1) diagnosed from 2001 to 2006 at our Department. There were
      four female and three male patients, mean age 46.1 and 49 years, respectively.
      All patients showed neurofibromas accompanied by fibromas, cafe au lait spots,
      cases showed five axillary freckling (lentigines) and one case showed five
      plexiform neurofibromas and pruritus belonging to NF1 category. All patients had
      affected first degree relatives. Systemic findings were rare and included optic
      glioma in one case and Lisch hamartoma nodules in three cases. In all cases, the
      diagnosis was established according to the National Institutes of Health
      criteria, including at least two of the diagnostic criteria for NF1 diagnosis.
      None of our cases had malignancies or gastrointestinal tract involvement.

PMID- 17010268
TI  - Update on dermal substitutes.
AB  - Tissue-engineered biological dressings offer promise in the treatment of burns,
      chronic ulcers, donor site and other surgical wounds, and a variety of
      dermatologic conditions. Despite this promise, cellular tissue-engineered
      products such a Dermagraft and Apligraf have suffered setbacks in recent years
      with a lower market share than the commercial promoters of these products
      anticipated. AlloDerm acellular dermal matrix, an older technology than these
      cell-based products, has made strong progress in winning over clinicians in
      various disciplines. Similarly, Integra Bilayer Matrix Wound Dressing (BMWD)
      continues to gain acceptance beyond its original burn audience. A review on the
      products is offered.

PMID- 17010269
TI  - Topical management of psoriasis - corticosteroids and sparing corticosteroid
      therapy.
AB  - Psoriasis is a complex disease that requires safe, long-term treatment. Topical
      steroid therapy, topical non-steroid therapy only, and a combination of various
      topical therapies in the treatment of mild to moderate forms of psoriasis are
      presented. Topical therapy includes corticosteroids, vitamin D3 analogs,
      retinoids, tars, anthralin, keratolytics, and topical immunomodulators. While
      most medications are approved for use as a single agent in the treatment of
      psoriasis, some of these drugs are most effective when used in combination with
      topical corticosteroids. Topical therapy is generally administered for mild and
      localized forms of psoriasis, whereas phototherapy and systemic therapy are
      reserved for extensive lesions and more severe forms of the disease. Individual
      approach is absolutely necessary in each patient with psoriasis.

PMID- 17010270
TI  - Most common oral alterations in the elderly--a review.
AB  - The population of Brazil is experiencing a fast and progressive aging process.
      Oral mucosa, which has a function as a barrier, is compromised by the aging
      process, allowing the action of predisposing agents. The older the population,
      the greater is the prevalence of lesions in oral mucosa. The causes may be
      neoplastic, infectious, bone pathologies, oral manifestations of systemic
      diseases, nutritional deficiencies, dental prostheses, medicaments, and bullous
      diseases, among others. Examination of the oral cavity should be carried out as
      an annual routine, and as a preventive measure for the entire elderly population,
      in order to reduce the morbidity and mortality from these diseases.

PMID- 17010273
TI  - Insect stings.

PMID- 17010271
TI  - A hundred years of "Allergy" Clemens von Pirquet's essay "Allergie", published on
      July 24, 1906 in Munchener Medizinische Wochenschrift.

PMID- 17010274
TI  - The human papillomavirus vaccines.
AB  - Genital human papillomavirus (HPV) infection is the most common sexually
      transmitted infection (STI) among sexually active couples. Its annual incidence
      is approximately 5.5 million. Overall, an estimated 75% of sexually active men
      and women have been exposed to HPV at some point in their lives. HPV-16 and -18
      account for about 70% of cancers of the cervix, vagina and anus, and for about
      30%-40% of cancers of the vulva, penis and orophaynx. Cancer of the cervix uteri
      is the second most cancer among women worldwide. Cancer of the penis is a rare
      cancer, accounting for less than 0.5% of cancers in men. Spontaneous clearance of
      HPV infection is accompanied by humoral and cellular immune response against
      virus-specific antigens. Two vaccines, prophylactic and therapeutic ones, are
      considered. Prophylactic vaccines use L1 and L2 capsid proteins to induce
      production of conformationally-specific antibodies. They block HPV infection.
      Lone L1 and L2 proteins self-assemble into a capsid that is identical to the
      complete virion. In this way, an antibody-mediated response is induced before the
      body actually comes into contact with the live virion. Therapeutic vaccines are
      being developed to protect HPV-positive persons against tumor development. For
      these vaccines, researchers are targeting the activity of the E6 and E7
      oncoproteines.On June 8, 2006, the U.S. Food and Drug Administration (FDA)
      approved an HPV vaccine for clinical use. The HPV vaccine that has been approved
      is the quadrivalent vaccine that consists of recombinant viral-like particles
      (VLPs) of HPV 6, 11, 16, 18 mixed with an aluminum-containing adjuvant. It is
      manufactured by Merck & Co., Inc. and sold under the name of Gardasil?. The new
      vaccine is approved for use in females 9-26 years of age. The primary target
      population for vaccination should be females aged 11-12 years. However,
      vaccination can be given to girls as young as 9 years of age. Vaccination can
      receive women aged 13-26 years who have been sexually active. There are still no
      data on the vaccine efficacy in women older than 26, and currently no data to
      demonstrate the efficacy of vaccination in males; male subjects should not be
      vaccinated until such data become available. The vaccine is to be administered
      intramuscularly either into the deltoid muscle of the arm or the high
      anteriolateral area of the leg. Each patient receives three 0.5 mL doses given
      according to the following schedule: first dose is given at the elected date,
      second dose two months after the first dose, and third dose six months after the
      first dose. According to statements from Merck, the list price of the vaccine is
      120 USD per dose. GlaxoSmithKline is now conducting a phase III trial of a
      bivalent (HPV 16, 18) vaccine, and it is going to be presented under the name of
      Cervarix. Similar results to those obtained with the quadrivalent HPV vaccine
      have been reported with the bivalent vaccine. It is expected to be released in
      June next year. Evaluation of the HPV vaccine efficiency in preventing dysplasia
      and cancer has been recommended as a globally accepted endpoint for population
      based studies.

PMID- 17010275
TI  - Comparative MO investigation of hindered rotation and thermal decomposition of
      carbamates and thiocarbamates.
AB  - Investigation of hindered rotation in carbamates reveals the high flexibility and
      ionic character of the CN bond as compared to common amides. This flexibility
      decreases in the case of thiocarbamates. The mechanism of activation of
      carbamates has been explored. Computations have proven the possibility of
      formation of an intramolecular H-bond in carbamates and thiocarbamates. This
      intramolecular H-bond is formed immediately after protonation of the carbamate.
      The possibility of formation of zwitterions as intermediates in the decomposition
      of carbamic and dithiocarbamic acids is discussed.

PMID- 17010276
TI  - The physicochemical state of protoporphyrin IX in aqueous solution investigated
      by fluorescence and light scattering.
AB  - Fluorescence spectros copy and light scattering have been used to investigate the
      physicochemical behaviour of protoporphyrin IX in aqueous solutions. In the
      alkaline range large micelles are formed with a hydrodynamic radius of 130 nm and
      a molecular mass of 5.0 x 10(7) Da. The micelles are fluorescent with an emission
      maximum at 620 nm. A pH lowering caused quenching of the micelle fluorescence. On
      a collision encounter these micelles will disintegrate and they are reformed by
      nucleation of collision fragments. From measurements of the fluorescence
      intensity of the micelles versus total concentration an equilibrium constant of
      4.0 x 10(6) M(-1) was found for this collision-nucleation process. In the pH
      range between 6 and 3 another micelle type of twice the size of those in the
      alkaline range was stable with respect to the solute. These micelles have free
      base porphyrin fluorescence with an emission maximum at 634 nm. A lowering of the
      pH below unity causes disintegration of these micelles and monomer fluorescence
      from the protoporphyrin dication was observed.

PMID- 17010277
TI  - Sugar adducts with alkaline earth metal ions. Interaction of L-arabinose with
      Sr(II) and Ba(II) ions and the effects of metal ion binding on the sugar anomeric
      configurations.
AB  - The reaction between L-arabinose and hydrated Sr(II) or Ba(II) halide salts has
      been studied in H2O solution and adducts of the type M(L-arabinose)X(2).4H(2)O,
      where M = Sr(II) or Ba(II) and X = Cl- or Br- have been isolated and
      characterized by means of Fourier transform infrared spectroscopy, 1H-NMR
      spectroscopy, molar conductivity and X-ray powder diffraction measurements. Due
      to the marked spectral similarities with those of the structurally known Ca(L
      arabinose)X2 . 4H2O (X= Cl- or Br-) compounds, the Sr(II) and the BA(II) ions are
      eight-coordinated, binding to two l-arabinose molecules via O1, O5 of the first
      and O3, O4 of the second sugar moiety and to four H2O molecules. 1H-NMR
      spectroscopy indicated that the free L-arabinose has the beta-anomer
      configuration in aqueous solution, whereas the alpha-anomer isomer is preferred
      by Mg(II), Ca(II), Sr(II) and Ba(II) ions, on complexation.

PMID- 17010278
TI  - A simple theoretical model of steady-state electrogenic transfer of reactive
      species across membranes. The case of Chara corallina.
AB  - Transfer across membranes is treated for simultaneous active pumping and passive
      flow of the main ionic constituents of plant cells. The chemical equilibrium
      conditions for H2CO3 and H2O dissociation prevailing in the external and internal
      solutions are taken into account. Our model assumes steady-state conditions, zero
      electrical current, electroneutrality inside the membrane and, in both solutions,
      finite space charge densities in two diffuse regions in contact with both sides
      of the membrane. A computer program has been developed for the integration of a
      set of flux equations. The results are displayed in terms of ionic flux
      parameters, each proportional to the ionic pump flow and to the reciprocal of the
      passive ionic mobility. The discussion emphasizes the role of anion inward
      pumping and of non-diffusible anions. The cationic pumps serve to establish
      different ionic balances in the cell. Transmembrane (bulk to bulk) proton pumping
      affects essentially the pH regulation in the cell.

PMID- 17010279
TI  - Viscosity behaviour and persistence length of sodium xanthan in aqueous sodium
      chloride.
AB  - Zero-shear-rate intrinsic viscosities [eta] of sodium xanthan in aqueous NACl at
      25 degrees C were determined for five samples ranging in weight- average
      molecular weight from 2 x 10(5) to 4 x 10(6) at salt concentrations Cs between
      0.005 and 1 M, at which the polysaccharide maintains its double-helical
      structure. The measured [eta] for every sample was almost independent of Cs, in
      contrast to usual observations on flexible polyelectrolytes. The persistence
      length q of sodium xanthan was determined as a function of Cs by use of the
      theory of Yamakawa et al. for [eta] of an unperturbed worm-like cylinder, and
      from its Cs dependence the intrinsic persistence length q(o) ( = q at infinite
      ionic strength) was estimated to be 106 nm. This q(o) value was roughly twice as
      large as that of double-stranded DNA, indicating a high intrinsic rigidity of the
      xanthan double helix. The electrostatic contribution ( = q - q(o)) to q was only
      about 10% even at the lowest Cs of 0.005 M. Thus, it was concluded that above Cs
      = 0.005 M, the double- helical structure of sodium xanthan is hardly stiffened by
      electrostatic interactions between charged groups.

PMID- 17010281
TI  - Influence of solvent, anion and presence of nitrogen in the ring structure on the
      mechanism of complexation of alkali metal cations with crown ethers.
AB  - The mechanism of complexation of alkali metal cations with macrocyclic ligands
      such as the simple crown ethers and the role of desolvation vs. ligand
      rearrangement are discussed. The unique role of water solvent in the rate
      determining step of complexations in aqueous solutions is brought into focus. The
      competitive role of the anion, which becomes of paramount importance in solvents
      of low permittivity, is reiterated. Monoazo crown ethers are shown to possess
      isomeric equilibria in methanol solvent. The rate-determining process for the
      first step of complexation of these macrocycles with Na+ in methanol appears to
      be the rearrangement of the ligand through inversion to an exo position of the
      nitrogen lone electron pair. The rate-determining step of the overall
      complexation is the entrance of the Na+ into the ring with (possibly) concomitant
      rotation of the lone electron of the nitrogen to an endo configuration.

PMID- 17010282
TI  - Computation of optical motion by movement detectors.
AB  - The first part of this paper deals with a system-theoretical approach for the
      decomposition of multi-input systems into the sum of simpler systems. This
      approach is applied here to analyse the algorithm which represents the
      computations underlying the extraction of motion information from the optical
      environment by biological movement detectors. The second part concentrates on a
      specific model for motion computation known to be realized by the visual system
      of insects and of man. These detectors provide the visual system with information
      on both the velocity and structural properties of a moving pattern. In the third
      part of this article the properties of two-dimensional arrays of movement
      detectors are analyzed and their relations to meaningful physiological responses
      are discussed.

PMID- 17010283
TI  - Structure of halophilic malate dehydrogenase in multimolar KCl solutions from
      neutron scattering and ultracentrifugation.
AB  - The structure and solvent interactions of malate dehydrogenase from Halobacterium
      marismortui in multimolar KCl solvents are found to be similar to those in
      multimolar NACl solvents reported previously (G. Zaccai, E. Wachtel and H.
      Eisenberg, J. Mol. Biol. 190 (1986) 97). KCl rather than NaCl is predominant in
      physiological medium. At salt concentrations up to about 3.0 M, the protein (a
      dimer of M 87000 g/mol) can be considered to occupy an invariant volume in which
      it is associated with about 4100 molecules of water and about 520 molecules of
      salt. At very low resolution, the enzyme particle appears to have a compact
      protein core and protruding protein parts in interaction with the water and salt
      components, structural features that are not observed in non-halophilic
      mitochondrial malate dehydrogenase. The above conclusions were drawn from the
      analysis of neutron scattering and ultracentrifugation data, and the
      complementarity of these approaches is discussed extensively.

PMID- 17010284
TI  - Three-dimensional representation of chemical gradients.
AB  - Perspective display techniques are applied to chemical and biochemical data sets.
      These represent spatially distributed gradients of reactive compounds that
      participate in pattern-formation processes due to reaction-diffusion or reaction
      convection coupling. The patterns form in thin solution layers and are observed
      as chemical waves in the Belousov-Zhabotinskii reaction, as convection-induced
      stationary structures during oscillating glycolysis in yeast cytoplasm, and as
      the diffusive spreading of enzyme-catalyzed metabolic turnover in a substrate
      layer. The digital data are measured with a two-dimensional spectrophotometer
      based on a computerized video equipment with high spatial, temporal and intensity
      resolution. By application of three-dimensional procedures detailed structural
      properties of chemical and biochemical model systems will be presented yielding
      localization of reaction and transport events.

PMID- 17010285
TI  - Forster-type energy transfer. Simultaneous 'forward' and 'reverse' transfer
      between unlike fluorophores.
AB  - The general case of Forster-type energy transfer is that in which energy is
      exchanged in both directions between two unlike fluorophores. In such cases,
      energy is transferred from the conventionally defined donor to the conventionally
      defined acceptor (forward transfer) and at the same time from the acceptor to the
      donor (reverse transfer). Expressions are derived to describe the fluorescence
      intensities and lifetimes of fluorophores undergoing simultaneous forward and
      reverse transfer; these are compared with corresponding quantities for the case
      more usually considered, in which only forward transfer is significant. It is
      shown that the presence of reverse transfer removes the distinction between donor
      and acceptor, and allows such anomalous effects as 'acceptor quenching'. A
      confirmatory example is described. It is shown that the equations generally used
      in distance determination by steady-state fluorescence spectroscopy can also be
      applied in the presence of reverse transfer, if a correction term is included;
      however, for lifetime spectroscopy the correction is more complex.

PMID- 17010286
TI  - Relation of growth process to spatial patterns of electric potential and enzyme
      activity in bean roots.
AB  - The electric spatial pattern and invertase activity distribution in growing roots
      of azuki bean (Phaseolus chrysanthos) have been studied. The electric potential
      near the surface along the root showed a banding pattern with a spatial period of
      about 2 cm. It was found that the enzyme activity has a peak around 3-7 mm from
      the root tip, in good agreement with the position of the first peak of the
      electric potential, which is located a little behind the elongation zone. An
      inhomogeneous distribution of ATP content was also detected along the root.
      Experiments on the electric isolation of the elongation zone from the mature zone
      and acidification treatment showed that H+ is transported from the mature-side to
      elongation-side regions, causing tip elongation through an acid-growth mechanism.
      Both acidification and electric disturbance on growing roots affected growth
      significantly. Simultaneous measurements of electric potential and enzyme
      activity clearly showed a good correlation between these two quantities and
      growth speed. From an analogy with the Characean banding, the spatio-temporal
      organization via the cell membrane in electric potential and enzyme activity can
      be regarded as a dissipative structure arising far from equilibrium. These
      experimental results can be interpreted with a new mechanism that the dissipative
      structure is formed spontaneously along the whole root, accompanied by energy
      metabolism, to make H+ flow into the root tip.

PMID- 17010287
TI  - Conformational studies of A23187 with mono-, di- and trivalent metal ions by
      circular dichroism spectroscopy.
AB  - CD studies carried out on A23187 indicate a solvent-dependent conformation for
      the free acid. Alkali metal ions were found to bind to the ionophore weakly.
      Divalent metal ions such as Mg2+, Ca2+, Sr2+, Ba2+ and Co2+ and trivalent
      lanthanide metal ions like La3+ were found to form predominantly 2:1 (ionophore
      metal ion) complexes at low concentrations of metal ions, but both 2:1 and 1:1
      complexes were formed with increasing salt concentration. Mg2+ and Co2+ exhibit
      similar CD behaviour that differs from that observed for the other divalent and
      lanthanide metal ions. The structure of 2:1 complexes involves two ligand
      molecules coordinated to the metal ion through the carboxylate oxygen,
      benzoxazole nitrogen and keto-pyrrole oxygen from each ligand molecule along with
      one or more solvent molecules. Values of the binding constant were determined for
      2:1 complexes of the ionophore with divalent and lanthanide metal ions.

PMID- 17010288
TI  - Theory of electric dissipative structure in Characean internode.
AB  - A band-type alternating pattern of acidic and alkaline regions formed along the
      Characean cell wall is discussed theoretically. The model system is constructed
      from linear diffusion equations for the concentration of H+ outside the internode
      and in the protoplasm. The plasmalemma is taken as a boundary transporting H+
      under energy supply by light. The sizes of the protoplasm and extracellular water
      phase are taken into account explicitly in the present model system to reproduce
      qualitatively the characteristics observed in various types of experiments.
      Theoretical analysis shows that the band pattern belongs to dissipative
      structures emerging far from equilibrium, and is stabilized through the electric
      current loops produced by locally activated electrogenic H+ pumps and spatially
      separated passive H+ influx (or OH- efflux) across the membrane. Both the
      numerical calculation and the theoretical analysis using a generalized time
      dependent Ginzburg-Landau equation reveal the following points: (i) the intemodal
      cell with a larger vacuole in a smaller size of the extracellular water phase
      tends to exhibit a clearer band pattern; (ii) the increase in viscosity of the
      external aqueous medium makes the bands appear more easily and, furthermore,
      distinctly; (iii) the change in size of the extracellular water phase
      significantly affects the kinetics of the pattern- formation process. These
      results are interpreted reasonably by taking account of the electric current
      circulating between the acidic and alkaline regions.

PMID- 17010289
TI  - Conductometric analysis of the competition between monovalent and divalent
      counterions in their interaction with polyelectrolytes.
AB  - A procedure is described for the analysis of the conductivity of solutions of
      anionic polyelectrolytes in which both mono- and divalent counterions are
      present. The method is based on analysis of the relation between the overall
      conductivity of the system and the conductivity of the individual monovalent
      cations which are only electrostatically (non-specifically) bound. The system is
      described in terms of the two-state approach, implying that the counterions are
      considered to be either fully bound to the polyion or completely free. The
      potentialities of the proposed method are explored by studying solutions of
      alkali polyacrylates with and without added zinc nitrate at several alkali
      nitrate concentrations. The results give a picture of the composition of the
      counterionic atmosphere around the polyion in systems with both mono- and
      divalent counterions present. To a certain degree, the divalent ion Zn(II) was
      found to be bound quantitatively by the polyion. The composition of the
      counterionic atmosphere around the polyion was largely independent of alkali
      nitrate concentration when the latter was present in not too large an excess with
      respect to both Zn(II) and the charged monomers.

PMID- 17010290
TI  - Molecular and macroscopic aspects of cavity formation in the hydrophobic effect.
AB  - The formation of a cavity in water is a conceptual preliminary to the dissolution
      of a nonpolar solute. The process is of biophysical importance because of its
      assumed primitive relation to hydrophobic factors affecting biological structure
      and function. In this paper, cavity formation by the isochoric deformation of a
      fluid specimen is investigated. Using both molecular and macroscopic descriptions
      of this process, the volume occupied by the fluid is held constant while the
      spherical specimen is reversibly deformed in differential steps until it
      surrounds a spherical cavity. The work of cavity formation results from the
      integration of energy changes generated directly from the forced, differential
      deformations of the equilibrium fluid structure; the heat of cavity formation is
      the integrated result of energy changes that accompany the nonforced,
      differential adjustments in the distribution of matter which modulate the average
      fluid structure during the process. This reversible isochoric deformation
      procedure for introducing the nonpolar system into the polar fluid is compared
      with the more familiar method that uses a reversible coupling parameter. Simple
      calculations based on the isochoric deformation method provide estimates of the
      free energy, internal energy, heat and entropy of cavity formation that agree
      with values from the scaled particle method.

PMID- 17010291
TI  - Influence of torus on the capacitance of asymmetrical phospholipid bilayers.
AB  - We have measured the specific capacitance of
      phosphatidylethanolamine/phosphatidylserine membranes formed from monolayers. The
      membranes were built across Teflon films whose thickness varied from 6 to 25 mum.
      The building up of the membranes was followed by recording the capacitance of the
      membranes during the entire process of their formation. It is observed that the
      specific capacitance increases by about 10% as the thickness of the film is
      increased. Furthermore, during formation of the membrane it is observed that the
      capacitance values increased markedly immediately before the membranes are
      completely formed and then suddenly decrease to their normal values when formed
      (closing-off phenomenon). These results have led us to propose that the
      transition region known to surround membranes formed from monolayers may affect
      the capacitance values measured for such membranes. However, this effect is
      indirect in the sense that the composition (most likely in the form of inverted
      micelles) of the transition region will ultimately modify the
      hydrophobic/hydrophilic barrier in the bilayer by affecting the lateral tension
      known to exist in such membranes and, as a consequence, the average molecular
      area occupied by a phospholipid molecule in the bilayer. By such a mechanism, one
      can rationalize our experimental finding that the membrane capacitance varies as
      a function of the partition thickness across which they are prepared. It also
      rationalizes the large fluctuations in capacitance values usually found in the
      literature for such membranes as well as, at least in part, the closing-off
      phenomenon.

PMID- 17010292
TI  - Effective propagators for quenched disorder in linear polymers.
AB  - A chain conformation space path integral theory is implemented to study the
      statistics of inhomogeneous polymers randomly constructed from two different
      kinds of monomers. A replica approach analogous to that used in spin glass
      systems is adopted to average over the quenched randomness. A perturbative
      analysis requires mixed propagators coupling identical replicas of an arbitrary
      sequence of monomers, Making use of these effective propagators we estimate the
      effect of the quenched disorder on intra-chain interactions and calculate the
      asymptotic behavior of the system in the limit of very large chains. This
      thermodynamic limit is analyzed comparing the effective Gibbs measure determined
      by the effective Hamiltonian with the Gibbs measure for a homogeneous polymer
      system where the intra-chain interactions correspond to the averaged interactions
      of the original system.

PMID- 17010293
TI  - Circular dichroism and magnetic circular dichroism spectra of chlorophylls a and
      b in nematic liquid crystals. II. Magnetic circular dichroism spectra.
AB  - Absorption and magnetic circular dichroism (MCD) spectra are reported for
      chlorophyll (Chl) a and Chl b dissolved in nematic liquid crystal solvents. The
      spectra were measured with the dye molecules oriented uniaxially along the
      direction of. the magnetic field and measuring light beam. It is significant that
      under such conditions the MCD spectra recorded in the wavelength region of the Q
      and Soret bands of the chlorophyll are essentially unchanged with respect to
      rotation of the sample cell around this axis, even though there is almost
      complete orientation of the chlorophyll molecules by the liquid crystals. The MCD
      spectra of Chl a and b in the nematic liquid crystal solvents used in this study
      are surprisingly similar to the spectra obtained under isotropic conditions.
      These results illustrate an important technique with which to examine the optical
      spectra of dyes oriented in liquid crystal matrices in which the anisotropic
      effects can be reduced the negligible proportions by the application of a strong
      magnetic field parallel to the direction of the measuring light beam. The first
      deconvolution calculations are reported that describe the deconvolution of pairs
      of absorption and MCD spectra, in the Q and B band regions, for both Chl a and b.
      The spectral analysis to obtain quantitative estimates of transition energies was
      accomplished by carrying out detailed deconvolution calculations in which the
      both the absorption and MCD spectral envelopes were fitted with the same number
      of components; each pair of components had the same hand centres and bandwidth
      values. This procedure resulted in an assignment of each of the main transitions
      in the absorption spectra of both Chl a and b. Chl a is clearly monomeric, with
      Qy, Qx, By and Bx located at 671, 582, 439 and 431 nm, respectively. Analysis of
      the spectral data for Chl b located Qy, By and Bx, at 662, 476 and 464 nm,
      respectively.

PMID- 17010294
TI  - Studies on the interaction between polyion and counterions by sound velocity
      (II).
AB  - Sound velocities in polyacrylate solutions neutralized by tetraalkylammonium
      hydroxide were measured at various concentrations of added NACl. From the
      results, the degree of counterion binding to polyion and the extent of the
      changes in hydration volume due to ion binding were determined as a function of
      the degree of neutralization, alpha. The ion binding accompanying the volume
      changes appeared above about alpha = 0.6 and the ion binding process depended on
      the charge density of the polyion. The effect of the size of the
      tetraalkylammonium ion on ion binding was negligibly small.

PMID- 17010295
TI  - Mechanical denaturation of globular protein in the solid state.
AB  - A method for taking stress-strain diagrams in microsamples prepared from
      glutaraldehyde-treated monocrystals and amorphous films of hen egg-white lysozyme
      has been developed. Analysis of the diagrams has shown that the deformation obeys
      Hooke's law within 0-2%. Upon further deformation of a crystalline sample (up to
      6-10%), when a critical stress, sigma(cr), is reached, the protein molecules in
      the sample denature and become greatly extended. Depending on the crystal type
      and crystallographic direction, the sample length increases 2-4 times. The
      critical stress is essentially dependent on the factors affecting intra- and
      intermolecular interactions: temperature, hydration level and urea concentration.
      Mechanisms for mechanical denaturation are proposed.

PMID- 17010296
TI  - The charge effects of the self-diffusion constant of bovine mercaptalbumin.
AB  - The charge effect on the translational self-diffusion constant, D, of
      polyelectrolytes has been quantitatively analyzed based on dynamic light
      scattering experiments. Perfectly monodisperse bovine mercaptalbumin has been
      used at low pH as a positively charged polyelectrolyte sample. Completely linear
      plots of log{g2(t)-1} vs. time t have been obtained for uncharged states of the
      protein, for the cor relation function of the scattered light intensity, g2(t).
      The plots deviate from linearity as polyions bear the charges. The D values for
      various ionic states, obtained from the initial slopes of the plots, have been
      analyzed using the simple theory of Imai and Mandel (N. Imai and M. Mandel,
      Macromolecules 15 (1982) 1562) derived based on the Onsager-Navier-Stokes
      equation for solvent flow with counterion distribution around a polyion. It has
      turned out that the experimental D values coincide well with the theory and that
      the characteristic nature of D can be elucidated principally from the charge
      effect.

PMID- 17010297
TI  - Vaginal paravaginal repair with porcine dermal reinforcement: correction of
      advanced anterior vaginal prolapse.
AB  - OBJECTIVE: The objective of the study was to determine the efficacy of the
      vaginal paravaginal repair using porcine dermal graft reinforcement for the
      correction of advanced anterior vaginal prolapse. STUDY DESIGN: One hundred
      eleven women underwent reinforced vaginal paravaginal repair between September
      2001 and January 2004 and met our inclusion criteria. Postoperatively patients
      were evaluated at 6 weeks, 6 months, and yearly thereafter. Objective cure was
      defined as point Ba -1 or less. RESULTS: Eighty-nine of the 111 (80%) patients
      were available for follow-up. Mean age of patients was 59.5 +/- 11.6 years (range
      26 to 82), mean body mass index was 29 +/- 5.5 (range 20 to 44), and median
      parity was 3 (range 0 to 15). Mean follow-up was 24 +/- 10.1 months (range 6 to
      44) with minimum follow-up required for cure of 12 months. Overall cure rate was
      78% (68 of 89). Data were analyzed using the Wilcoxon rank test. CONCLUSION: The
      reinforced vaginal paravaginal repair procedure is safe and effective for
      correction of advanced anterior vaginal prolapse.

PMID- 17010299
TI  - Characterization of the metal-binding site of human prolactin by site-specific
      metal-catalyzed oxidation.
AB  - Site-specific metal-catalyzed oxidation (MCO) was applied to characterize the
      metal-binding site (MBS) of recombinant human prolactin (hPRL), which belongs to
      the hematopoietic cytokine family. Copper and ascorbate of various concentrations
      were used to initiate the oxidation of hPRL, and the oxidation-sensitive motifs
      were characterized and quantitated by mass spectrometry. Based on the results
      obtained with 10 microM Cu(2+) and 0.3-2.0mM ascorbate, we propose that the MBS
      in hPRL is composed of His27, His30, and His173. This result shows the similarity
      of hPRL to human growth hormone (hGH), a member of the same family as hPRL, where
      the MBS is composed of His18, His21, and Glu174.

PMID- 17010298
TI  - Measuring "free" iron levels in Caenorhabditis elegans using low-temperature
      Fe(III) electron paramagnetic resonance spectroscopy.
AB  - Oxidative stress, caused by free radicals within the body, has been associated
      with the process of aging and many human diseases. Because free radicals, in
      particular superoxide, are difficult to measure, an alternative indirect method
      for measuring oxidative stress levels has been used successfully in Escherichia
      coli and yeast. This method is based on a proposed connection between elevated
      superoxide levels and release of iron from solvent-exposed [4Fe-4S] enzyme
      clusters that eventually leads to an increase in hydroxyl radical production. In
      past studies using bacteria and yeast, a positive correlation was found between
      superoxide production or oxidative stress due to superoxide within the organism
      and electron paramagnetic resonance (EPR) detectable "free" iron levels. In the
      current study, we have developed a reliable and efficient method for measuring
      "free" iron levels in Caenorhabditis elegans using low-temperature Fe(III) EPR at
      g=4.3. This method uses synchronized worm cultures grown on plates that are
      homogenized and treated with desferrioxamine, an Fe(III) chelator, prior to
      packing the EPR tube. Homogenization was found not to alter "free" iron levels,
      whereas desferrioxamine treatment significantly raised these levels, indicating
      the presence of both Fe(II) and Fe(III) in the "free" iron pool. The correlation
      between free radical levels and the observed "free" iron levels was examined by
      using heat stress and paraquat treatment. The intensity of the Fe(III) EPR
      signal, and thus the concentration of the "free" iron pool, varied with the
      treatments that altered radical levels without changing the total iron levels.
      This study provides the groundwork needed to uncover the correlation among
      oxidative stress, "free" iron levels, and longevity in C. elegans.

PMID- 17010300
TI  - Construction of methylation-sensitive partial restriction bacterial artificial
      chromosome libraries in maize.

PMID- 17010301
TI  - Association between objective and subjective measurements of comfort and
      discomfort in hand tools.
AB  - In the current study, the relationship between objective measurements and
      subjective experienced comfort and discomfort in using handsaws was examined.
      Twelve carpenters evaluated five different handsaws. Objective measures of
      contact pressure (average pressure, pressure area and pressure-time (P-t)
      integral) in static and dynamic conditions, muscle activity (electromyography) of
      five muscles of the upper extremity, and productivity were obtained during a
      sawing task. Subjective comfort and discomfort were assessed using the comfort
      questionnaire for hand tools and a scale for local perceived discomfort (LPD). We
      did not find any relationship between muscle activity and comfort or discomfort.
      The P-t integral during the static measurement (beta=-0.24, p<0.01) was the best
      predictor of comfort and the pressure area during static measurement was the best
      predictor of LPD (beta=0.45, p<0.01). Additionally, productivity was highly
      correlated to comfort (beta=0.31, p<0.01) and discomfort (beta=-0.49, p<0.01).

PMID- 17010302
TI  - Physiological and psychophysical responses in handling maximum acceptable weights
      under different footwear--floor friction conditions.
AB  - A study on combined manual materials-handling tasks performed on floors under
      three friction levels was conducted. Eight male subjects participated in the
      study. The maximum acceptable weight of handling, including lifting, carrying for
      3m, lowering, and walking 3m back at twice per minute was determined. The subject
      then performed the same tasks for 10 min. Heart rate, Vo2, energy efficiency,
      perceived sense of slip, and rating of perceived exertion for whole body strain
      were measured. The results showed that the effects of friction level on the
      maximum acceptable weights of handling, perceived sense of slip, Vo2, and energy
      efficiency were statistically significant (p<or=0.0006). As the friction level
      increased from low to high, the maximum acceptable weights of handling increased
      from 8.15 to 9.34 kg. The energy efficiency on the low friction condition (12.58
      kg/L/min) was significantly lower than those of the medium (15.73 kg/L/min) and
      high (15.38 kg/L/min) friction conditions. The perceived sense of slip was the
      highest (5.44) on the low-friction condition, followed by the medium-friction
      condition (3.58), and last the high-friction condition (1.84). The implication of
      this study was that friction level should be regarded as one of the major
      environmental factors in designing MMH tasks as it affected both physiological
      and psychophysical responses of the subjects. Low-friction footwear-floor
      interface should be avoided as it resulted in not only high scores of perceived
      sense of slip but also in low-energy efficiency utilized in the body.

PMID- 17010303
TI  - Thermal stability of trimeric light-harvesting chlorophyll a/b complex (LHCIIb)
      in liposomes of thylakoid lipids.
AB  - The major light-harvesting chlorophyll a/b complex (LHCIIb) of photosystem (PS)
      II functions by harvesting light energy and by limiting and balancing the energy
      flow directed towards the PSI and PSII reaction centers. The complex is
      predominantly trimeric; however, the monomeric form may play a role in one or
      several of the regulatory functions of LHCIIb. In this work the dissociation
      temperature was measured of trimeric LHCIIb isolated from Pisum thylakoids and
      inserted into liposomes made of various combinations of thylakoid lipids at
      various protein densities. Dissociation was measured by monitoring a trimer
      specific circular dichroism signal in the visible range. The LHCIIb density in
      the membrane significantly affected the trimer dissociation temperature ranging
      from 70 degrees C at an LHCIIb concentration comparable to or higher than the one
      in thylakoid grana, to 65 degrees C at the density estimated in stromal lamellae.
      Omitting one thylakoid lipid from the liposomes had virtually no effect on the
      thermal trimer stability in most cases except when digalactosyl diacylglycerol
      (DGDG) was omitted which caused a drop in the apparent dissociation temperature
      by 2 degrees C. In liposomes containing only one lipid species, DGDG and, even
      more so, monogalactosyl diacylglycerol (MGDG) increased the thermal stability of
      LHCIIb trimers whereas phosphatidyl diacylglycerol (PG) significantly decreased
      it. The lateral pressure exerted by the non-bilayer lipid MGDG did not
      significantly influence LHCII trimer stability.

PMID- 17010305
TI  - What is the function of nail biting: an analog assessment study.
AB  - OBJECTIVE: To compare the frequency of nail biting in 4 settings (interventions)
      designed to elicit the functions of nail biting and to compare the results with a
      self-report questionnaire about the functions of nail biting. DESIGN: Randomised
      allocation of participants to order of conditions. SETTING: University Psychology
      Department. SUBJECTS: Forty undergraduates who reported biting their nails.
      INTERVENTIONS: Left alone (boredom), solving maths problems (frustration),
      reprimanded for nail biting (contingent attention), continuous conversation
      (noncontingent attention). MAIN OUTCOME MEASURES: Number of times the
      undergraduates bit their nails. RESULTS: Nail biting occurred most often in two
      conditions, boredom and frustration. CONCLUSION: Nail biting in young adults
      occurs as a result of boredom or working on difficult problems, which may reflect
      a particular emotional state. It occurs least often when people are engaged in
      social interaction or when they are reprimanded for the behavior.

PMID- 17010304
TI  - Glycosphingolipids and drug resistance.
AB  - Drug resistance, an all too frequent characteristic of cancer, represents a
      serious barrier to successful treatment. Although many resistance mechanisms have
      been described, those that involve membrane-resident proteins belonging to the
      ABC (ATP binding cassette) transporter superfamily are of particular interest. In
      addition to cancer, the ABC transporter proteins are active in diseases such as
      malaria and leishmaniasis. A recent renaissance in lipid metabolism, specifically
      ceramide and sphingolipids, has fueled research and provided insight into the
      role of glycosphingolipids in multidrug resistance. This article reviews current
      knowledge on ceramide, glucosylceramide synthase and cerebrosides, and the
      relationship of these lipids to cellular response to anticancer agents.

PMID- 17010306
TI  - Guided self-help versus pure self-help for perfectionism: a randomised controlled
      trial.
AB  - Perfectionism is known to be a risk factor for the development and maintenance of
      obsessive-compulsive (OC) and depressive symptoms. The purpose of the present
      study was to test the effectiveness of a cognitive-behavioural self-help therapy
      for perfectionism, and to examine the effect of such treatment on OC and
      depressive symptomatology. The study compares the effectiveness of guided self
      help (GSH, n=24) with pure self-help (PSH, n=25) therapy. Both GSH and PSH were
      found to be effective in reducing perfectionism, and also in reducing OC and
      depressive symptomatology. Overall, participants in the GSH condition experienced
      greater symptom improvement than participants in the PSH condition, and treatment
      gains for both groups were largely maintained at 3-month follow-up. Twenty
      percent of PSH participants experienced clinically significant increases in
      depressive symptoms over the treatment and follow-up period (compared to 0% in
      the GSH condition), suggesting that PSH may be a less suitable strategy than GSH
      in treating this population. Overall, the findings suggest that self-help for
      perfectionism is effective in reducing OC and depressive symptomatology in non
      clinical individuals, with GSH being superior to PSH.

PMID- 17010307
TI  - Recurrent binge eating with and without the "undue influence of weight or shape
      on self-evaluation": implications for the diagnosis of binge eating disorder.
AB  - Levels of eating disorder psychopathology, impairment in psycho-social
      functioning and use of health services were compared among probable cases of
      binge eating disorder (BED) with and without extreme weight or shape concerns
      ("undue influence of weight or shape on self-evaluation") recruited from a large
      community sample of women. Data for obese non-binge eaters (n=457), also
      recruited from the community sample, and for a clinical sample of eating disorder
      patients (n=128), recruited separately, were included for comparative purposes.
      BED cases who reported extreme weight or shape concerns (n=51, 46.4%) had
      significantly higher levels of eating disorder psychopathology and functional
      impairment than those who did not report such concerns (n=59), after controlling
      for between-group differences in age and body weight. In addition, BED cases who
      reported extreme weight or shape concerns were more likely to have sought
      treatment for an eating or weight problem than those who did not. Whereas levels
      of eating disorder psychopathology and functional impairment were markedly
      elevated among BED cases with extreme weight or shape concerns, BED cases who did
      not report extreme weight or shape concerns resembled obese non-binge eaters in
      most respects. The findings support the inclusion of an undue influence of weight
      or shape on self-evaluation as a diagnostic criterion for BED. In the absence of
      this influence, eating disorders that otherwise resemble BED do not appear to be
      "clinically significant".

PMID- 17010308
TI  - Leukotriene D4 induces brain edema and enhances CysLT2 receptor-mediated
      aquaporin 4 expression.
AB  - Cysteinyl leukotrienes (including LTC(4), LTD(4), and LTE(4)), potent
      inflammatory mediators, can induce brain-blood barrier (BBB) disruption and brain
      edema. These reactions are mediated by their receptors, CysLT(1) and CysLT(2)
      receptors. On the other hand, aquaporin 4 (AQP4) primarily modulates brain water
      homeostasis and edema after various injuries. Here, we aimed to determine whether
      AQP4 is involved in LTD(4)-induced brain edema. LTD(4) (1ng in 0.5mul PBS)
      microinjection into the cortex increased endogenous IgG exudation (BBB
      disruption) and water content (brain edema), and enhanced AQP4 expression in
      mouse brain. The selective CysLT(1) receptor antagonist pranlukast inhibited the
      IgG exudation, but not the increased water content and AQP4 expression induced by
      LTD(4). In the cultured rat astrocytes, LTD(4) (10(-9)-10(-7)M, for 24h)
      similarly enhanced AQP4 expression. The enhanced AQP4 expression was inhibited by
      Bay u9773, a non-selective CysLT(1)/CysLT(2) receptor antagonist, but not by
      pranlukast. LTD(4) (10(-9)-10(-7)M) also induced the mRNA expression of CysLT(2)
      (not CysLT(1)) receptor in astrocytes. These results indicate that LTD(4)
      modulates brain edema; CysLT(1) receptor mediates vasogenic edema while CysLT(2)
      receptor may mediate cytotoxic edema via up-regulating AQP4 expression.

PMID- 17010309
TI  - ANP inhibits LPS-induced stimulation of rat microglial cells by suppressing NF
      kappaB and AP-1 activations.
AB  - Atrial natriuretic peptide (ANP) contributes to the inhibition of such causes of
      inflammation as the lipopolysaccharide (LPS)-induced productions of nitric oxide
      (NO) and proinflammatory cytokines [including interleukin-1 (IL-1)] in
      macrophages. In the present study we used primary cultures of rat brain
      macrophage-like cells (i.e., microglial cells) to investigate whether ANP binding
      to its receptors inhibits LPS-induced microglial activation via effects on the
      activation of the proinflammatory transcription factors NF-kappaB and AP-1. The
      productions of NO and IL-1, as well as morphological changes, were examined to
      assess LPS-induced activation of microglial cells. Our RT-PCR study revealed that
      rat microglial cells express the mRNAs for ANP receptors (types A, B, and C) and
      that for the ANP molecule. LPS (100 ng/ml)-stimulated microglial cells showed
      increases in nitrite (a relatively stable metabolite of NO) and IL-1
      concentrations, and in the expression of IL-1 mRNA, as well as a morphological
      change from an amoeboid shape to a multipolar (mostly bipolar, but sometimes
      tripolar) rod shape. These effects were all significantly inhibited by treatment
      with ANP (at 10(-6)M or less). The inhibition by ANP of the LPS-induced nitrite
      response was abrogated by a NP-receptor antagonist, HS-142-1 (100 ng/ml). NF
      kappaB and AP-1 activities were enhanced in LPS-stimulated microglial cells, and
      these enhancements were significantly suppressed by ANP (10(-6)M). These results
      suggest that ANP inhibits LPS-stimulated activities in microglial cells through
      activation of microglial ANP receptors, leading to inhibitions of NF-kappaB and
      AP-1.

PMID- 17010310
TI  - The acidic domain of hnRNPQ (NSAP1) has structural similarity to Barstar and
      binds to Apobec1.
AB  - Apobec1 edits the ApoB mRNA by deaminating nucleotide C(6666), which results in a
      codon change from Glutamate to stop, and subsequent expression of a truncated
      protein. Apobec1 is regulated by ACF (Apobec1 complementation factor) and hnRNPQ,
      which contains an N-terminal "acidic domain" (AcD) of unknown function, three RNA
      recognition motifs, and an Arg/Gly-rich region. Here, we modeled the structure of
      AcD using the bacterial protein Barstar as a template. Furthermore, we
      demonstrated by in vitro pull-down assays that 6xHis-AcD alone is able to
      interact with GST-Apobec1. Finally, we performed in silico phosphorylation of AcD
      and molecular dynamics studies, which indicate conformational changes in the
      phosphorylated form. The results of the latter studies were confirmed by in vitro
      phosphorylation of 6xHis-AcD by protein kinase C, mass spectrometry, and
      spectroscopic analyses. Our data suggest hnRNPQ interactions via its AcD with
      Apobec1 and that this interaction is regulated by the AcD phosphorylation.

PMID- 17010311
TI  - Regulation of Ca2+/calmodulin kinase II inhibitor alpha (CaMKIINalpha) in virus
      infected mouse brain.
AB  - The alpha and beta isoforms of rat Ca(2+)/calmodulin kinase II inhibitor
      (CaMKIINalpha/beta) expressed in brain or brain and testis, respectively, are
      potent inhibitors of Ca(2+)/calmodulin kinase II (CaMKII) in vitro. However, the
      regulation or function of CaMKIINalpha/beta in the central nervous system (CNS)
      is not known. In this study, we demonstrate that mouse CaMKIINalpha gene encodes
      a 2.9kb brain-specific transcript whose expression is downregulated in mouse
      brain during Japanese encephalitis virus (JEV) and rabies virus infection. The
      downregulation is specific for CaMKIINalpha but not CaMKIINbeta mRNA. In addition
      to these changes in CaMKIINalpha mRNA, distinct changes are also observed in the
      phosphorylation as well as subcellular localization of CaMKIIalpha leading to an
      increase in cytosolic CaMKII activity in JEV-infected mouse brain. The
      differential regulation of CaMKIIalpha and CaMKIINalpha during JEV infection
      suggests a possible role for these proteins in viral infection and/or virus
      induced neuropathogenesis in the CNS.

PMID- 17010312
TI  - Mutants of the deubiquitinating enzyme Ubp14 decipher pathway diversity of
      ubiquitin-proteasome linked protein degradation.
AB  - Selective proteolysis is an important regulatory mechanism in all cells. In
      eukaryotes, this process gains specificity by tagging proteins with the small
      protein ubiquitin. K48 linked polyubiquitin chains of four and more ubiquitin
      moieties target proteins for hydrolysis by the proteasome. Prior to degradation
      the polyubiquitin chain is removed from the protein, cleaved into single units,
      and recycled. The deubiquitinating enzyme Ubp14 is an important catalyst of this
      process. Mutants of Ubp14 had been shown to accumulate non-cleaved oligo- and
      polyubiquitin chains, which resulted in inhibition of overall ubiquitin
      proteasome linked proteolysis as well as in inhibition of degradation of some
      known substrates. Here we show that accumulation of ubiquitin chains due to
      defective Ubp14 does not uniformly lead to inhibition of ubiquitin-proteasome
      linked protein degradation. Instead, inhibition of degradation depends on the
      substrate tested. The results indicate the existence of different paths through
      which proteins enter the proteasome.

PMID- 17010313
TI  - Increased matrix metalloproteinase-3 mRNA expression in visceral fat in mice
      implanted with cultured preadipocytes.
AB  - Using preadipocyte implantation methods, we recently demonstrated that adipocytes
      in the visceral area change their function, as the expression of tumor necrosis
      factor-alpha (TNF-alpha) increases, thereby causing insulin resistance. In order
      to clarify the mechanism for changes in the function of adipocytes in visceral
      area, we examined the mRNA expression profiles in visceral fat tissue specimens.
      Four weeks after cell implantation, we performed a microarray analysis using the
      RNA of fat tissue specimens implanted either with 3T3-L1 cells or PBS alone.
      Sixty-three genes were thus isolated and the expression of matrix
      metalloproteinase-3 (MMP-3) mRNA was found to dramatically increase in the fat
      tissue specimens. The neutralization of MMP-3 protein inhibited adipogenesis and
      the free fatty acid-induced TNF-alpha secretion in 3T3-L1 adipocytes. These
      results suggest a potential role of MMP-3, which promotes the TNF-alpha
      secretion, thus contributing to the disturbance of the functions in the
      adipocytes which accumulate in the visceral area.

PMID- 17010314
TI  - Iptakalim protects PC12 cell against H2O2-induced oxidative injury via opening
      mitochondrial ATP-sensitive potassium channel.
AB  - The final common pathway in the demise of dopaminergic neurons in Parkinson's
      disease may involve oxidative stress and excitotoxicity. In this study, we
      examined the neuroprotective effects of a novel ATP-sensitive potassium channel
      (K(ATP)) opener, iptakalim (IPT), against H(2)O(2)-induced cytotoxicity in rat
      dopaminergic PC12 cells. Pretreatment with IPT could attenuate increased
      extracellular glutamate levels and inhibit calcium influxing induced by H(2)O(2).
      Moreover, IPT regulated the expressions of bcl-2 and bax which were responsible
      for inhibiting apoptosis in PC12 cells. These protective effects of IPT were
      abolished by selective mitoK(ATP) channel blocker 5-hydroxydecanoate. Therefore,
      IPT can protect PC12 cells against H(2)O(2)-induced oxidative injury via
      activating mitoK(ATP) channel.

PMID- 17010315
TI  - Disruption of focal adhesion kinase slows transendothelial migration of AU-565
      breast cancer cells.
AB  - Transendothelial migration of cancer cells from the vasculature into tissue
      stroma is a final step in the metastatic cascade, prior to formation of secondary
      tumors. Due to its role in 2-dimensional migration of cells on extracellular
      matrix proteins, we hypothesized that focal adhesion kinase (FAK) promotes
      transendothelial migration of cancer cells. AU-565 cells are weakly invasive
      metastatic breast adenocarcinoma cells that migrate through bovine lung
      microvessel endothelial cell monolayers. Electric cell-substrate impedance
      sensing detects a significant decrease in monolayer resistance upon addition of
      AU-565 cells. Immunofluorescence microscopy and filter-based migration assays
      demonstrate that this drop in resistance correlates with transendothelial
      migration. Transfection of AU-565 cells with FAK siRNA results in significantly
      diminished transendothelial migration of AU-565 cells within 15h. Expression of
      the dominant negative FAK inhibitor FAK-related non-kinase (FRNK) also results in
      delayed AU-565 transendothelial migration, whereas over-expression of wildtype
      FAK does not impact transendothelial migration substantially. These results
      demonstrate that FAK affects the rate of a key step in the metastatic cascade.

PMID- 17010316
TI  - Raf-1 kinase activation is uncoupled from downstream MEK/ERK pathway in cells
      treated with Src tyrosine kinase inhibitor PP2.
AB  - Recently we demonstrated that PP2 (4-amino-5-(4-chloro-phenyl)-7-(t
      butyl)pyrazolo[3,4-d]pyrimidine), a potent and selective inhibitor of the Src
      family tyrosine kinase, markedly enhanced Ras-independent activation of Raf-1 by
      the combination of phorbol myristate acetate (PMA) and hydrogen peroxide
      (H(2)O(2)). We report here that Raf-1 knockdown cells were significantly more
      sensitive to treatment of PP2 than control cells. This PP2-induced growth
      inhibition was found to be linked to decreased ERK and p38 activity.
      Interestingly, the growth of Sprouty knockdown cells appeared to be inhibited at
      earlier time points of PP2 treatment when compared with control cells.
      Unexpectedly, siRNA-mediated knockdown of Spry2, which is known to modulate the
      Ras/Raf/MAPK signal through feedback regulation, resulted in decreased Raf-1
      kinase activity. PP2 had limited effect on the ability of PMA/H(2)O(2) to induce
      significant phosphorylation of MEK/ERK proteins in both Spry2 knockdown and
      control cells, indicating that PP2-mediated activation of Raf-1 did not
      potentiate signaling through the downstream MEK/ERK pathway. Taken together our
      results suggest that Raf-1 signaling may be bypassed in PP2-treated cells by
      uncoupling from downstream MEK/ERK pathway.

PMID- 17010317
TI  - Sulindac, a nonsteroidal anti-inflammatory drug, selectively inhibits interferon
      gamma-induced expression of the chemokine CXCL9 gene in mouse macrophages.
AB  - Sulindac, a non-steroidal anti-inflammatory drug, has been shown to exert an anti
      tumor effect on several types of cancer. To determine the effect of sulindac on
      intracellular signaling pathways in host immune cells such as macrophages, we
      investigated the effect of the drug on interferon gamma (IFNgamma)-induced
      expression of signal transducer and activator of transcription 1 (STAT1) and
      other genes in mouse macrophage-like cell line RAW264.7 cells. Sulindac, but not
      aspirin or sodium salicylate, inhibited IFNgamma-induced expression of the CXC
      ligand 9 (CXCL9) mRNA, a chemokine for activated T cells, whereas the interferon
      induced expression of CXCL10 or IFN regulatory factor-1 was not affected by
      sulindac. Luciferase reporter assay demonstrated that sulindac inhibited IFNgamma
      induced promoter activity of the CXCL9 gene. Surprisingly, sulindac had no
      inhibitory effect on IFNgamma-induced STAT1 activation; however, constitutive
      nuclear factor kappaB activity was suppressed by the drug. These results indicate
      that sulindac selectively inhibited IFNgamma-inducible gene expression without
      inhibiting STAT1 activation.

PMID- 17010318
TI  - The use of heat-induced hydrolysis in immunohistochemistry on angiotensin II
      (AT1) receptors enhances the immunoreactivity in paraformaldehyde-fixed brain
      tissue of normotensive Sprague-Dawley rats.
AB  - The research on components of the renin-angiotensin system delivered a broad
      image of angiotensin II-binding sites. Especially, immunohistochemistry (IHC)
      provided an exact anatomical localization of the AT(1) receptor in the rat brain.
      Yet, controversial results between in vitro receptor autoradiography and IHC as
      well as between immunohistochemical studies using various antisera started a
      vehement discussion concerning specificity and cross-reactivity of these
      antisera. In particular the magnocellular subdivision of the paraventricular
      nucleus (PVN) and the supraoptic nucleus (SON) provided controversial results on
      the localization of AT(1) receptors. Both areas are known for angiotensin II
      induced release of vasopressin (VP) and oxytocin (OXT). To evaluate the
      significance of the appropriate method of antigen retrieval and its relevance for
      the detection of AT(1) receptors we performed IHC on AT(1) receptors in
      paraformaldehyde-fixed and paraffin-embedded brain tissue of Sprague-Dawley rats
      using either the detergent Triton X-100 or microwave oven heating. This study
      demonstrates that heat-induced hydrolysis enhances the quality and quantity of
      immunoreactivity (IR) in IHC on AT(1) receptors. In the organum vasculosum lamina
      terminalis and in the parvocellular subdivisions of the PVN we report a
      distribution of AT(1)-like-IR similar to that observed with other methods.
      However, in addition, we provide evidence that distinct AT(1)-like-IR is also
      localized in few magnocellular neurons of the PVN and in few parvocellular
      neurons of the dorsal SON but not in magnocellular neurons of the SON. Moreover,
      parallel IHC indicates that few magnocellular OXT- or VP-releasing neurons of the
      PVN as well as parvocellular OXT-releasing neurons of the SON do also contain
      AT(1) receptors.

PMID- 17010319
TI  - Nerve degeneration is prevented by a single intraneural apotransferrin injection
      into colchicine-injured sciatic nerves in the rat.
AB  - In this work, we have immunohistochemically analyzed the effects of single
      injections of apotransferrin (aTf) on the expression of myelin (myelin basic
      proteins [MBPs]) and axonal (protein gene product 9.5 [PGP 9.5] and beta(III)
      tubulin [beta(III)-tub]) proteins in colchicine-injected and crushed sciatic
      nerves of adult rats. A protein redistribution was seen in the distal stump of
      injured nerves, with the appearance of MBP- and PGP 9.5-immunoreactive (IR)
      clusters which occurred earlier in crushed nerves (3 days post-injury [PI]) as
      compared to colchicine-injected nerves (7 days PI). beta(III)-tub-IR clusters
      appeared at 1 day PI preceding the PGP 9.5- and MBP-IR clusters in colchicine
      injected nerves. With image analysis, the peak of clustering formation was found
      at 14 days PI for MBP and at 3 days PI for beta(III)-tub in colchicine-injected
      nerves. At 28 days of survival, the protein distribution patterns were almost
      normal. The intraneural application of aTf, at different concentrations (0.0005
      mg/ml, 0.005 mg/ml, 0.05 mg/ml, 0.5 mg/ml), prevented nerve degeneration produced
      by colchicine, with the appearance of only a small number of MBP- and beta(III)
      tub-IR clusters. However, aTf was not able to prevent clustering formation when
      the nerve was crushed, a kind of injury that also involves necrosis and blood
      flow alterations. The results suggest that aTf could prevent the colchicine
      effects by stabilizing the cytoskeleton proteins of the nerve fibers, avoiding
      the disruption of the axonal transport and thus the myelin degeneration.
      Transferrin is proposed as a complementary therapeutic avenue for treatment of
      cytotoxic nerve injuries.

PMID- 17010320
TI  - Glycine transporter 1 expression in the ventral respiratory group is restricted
      to protoplasmic astrocytes.
AB  - The lack of the glycine transporter 1 (GlyT1) leads to early postnatal death due
      to failure of respiratory network activity. Here we demonstrate a segregated
      expression of GlyT1 on different astroglial cell populations of the ventral
      respiratory group. In TgN(hGFAP-EGFP) mice a combined immunohistochemical and
      electrophysiological approach was used to define the cellular expression of GlyT1
      in the respiratory network. EGFP-labeled cells with outwardly rectifying current
      voltage relationship did not express glycine transporter 1, while GlyT1 was
      abundantly expressed in mature protoplasmic astrocytes, which are
      electrophysiologically characterized by a large potassium conductance, a more
      negative membrane potential and the expression of glutamate transporters. Taken
      together, the vital capacity for the clearance of extracellular glycine is
      restricted to a subpopulation of astroglial cells.

PMID- 17010322
TI  - Word comprehension facilitates object individuation in 10- and 11-month-old
      infants.
AB  - The present study investigated the role that comprehending words for objects
      plays in 10- and 11-month-old infants' ability to individuate those objects in a
      spatiotemporally ambiguous event. To do this, we employed an object individuation
      task in which infants were familiarized to two objects coming in and out from
      behind a screen in alternation, and then the screen was removed to reveal either
      both or only one of the objects. Results show that only when 10- and 11-month
      olds comprehend words for both objects seen do they exhibit looking behavior that
      is consistent with object individuation (i.e., looking longer when one of the
      objects is surreptitiously removed). Neither level of object permanence reasoning
      nor overall receptive vocabulary had an effect on performance in the object
      individuation task, indicating that the effect was specific to the immediate
      parameters of the situation, and not a function of overall precocity on the part
      of the succeeding infants. These results suggest that comprehending the words for
      occluded/disoccluded objects provides a kind of "glue" which allows infants to
      bind the mental index of an object with its perceptual features (thus
      precipitating the formation of two mental indexes, rather than one). They further
      suggest that a shift from object indexing driven by the where (dorsal) system to
      one which is driven by integration of the ventral and dorsal neural systems,
      usually not observed until 12 months of age, can be facilitated by word
      comprehension in 10- and 11-month-old infants.

PMID- 17010321
TI  - Synthesis, protein levels, activity, and phosphorylation state of tyrosine
      hydroxylase in mesoaccumbens and nigrostriatal dopamine pathways of chronically
      food-restricted rats.
AB  - Chronic food restriction (FR) enhances the rewarding and motor-activating effects
      of abused drugs, and is accompanied by changes in dopamine (DA) dynamics and
      increased D-1 DA receptor-mediated cell signaling and transcriptional responses
      in nucleus accumbens (NAc). However, little is known about effects of FR on DA
      synthetic activity in the mesoaccumbens and nigrostriatal pathways. In Experiment
      1 of the present study, tyrosine hydroxylase (TH) gene expression was measured in
      ventral tegmental area and substantia nigra, using real-time RT-PCR and in situ
      hybridization; no differences were observed between FR and ad libitum fed (AL)
      rats. In Experiment 2, TH protein levels, determined by Western blot, were found
      to be elevated in NAc and caudate-putamen (CPu) of FR relative to AL rats. In the
      absence of increased transcription, this may reflect a slowing of TH degradation.
      In Experiments 3 and 4, DA synthetic activity was assessed by Western blot
      measurement of TH phosphorylation at Ser40, and HPLC measurement of in vivo
      tyrosine hydroxylation rate, as reflected by DOPA accumulation following
      administration of a decarboxylase inhibitor (NSD-1015; 100 mg/kg, i.p.). Basal
      phospho-(Ser40)-TH levels did not differ between groups but DOPA accumulation was
      decreased by FR. Decreased DOPA synthesis, despite increased levels of TH
      protein, may reflect the inhibitory effect of increased DA binding to TH protein
      or decreased concentrations of cofactor tetrahydrobiopterin. Finally, in response
      to D-amphetamine (0.5 and 5.0 mg/kg, i.p.), phospho-(Ser40)-TH was selectively
      decreased in NAc of FR rats. This suggests increased feedback inhibition of DA
      synthesis-a possible consequence of postsynaptic receptor hypersensitivity, or
      increased extracellular DA concentration. These results indicate that FR
      increases TH protein levels, but may decrease the capacity for DA synthesis by
      decreasing TH activity. According to this scheme, the previously observed
      upregulation of striatal cell signaling and transcriptional responses to DA
      receptor agonist administration may include compensatory neuroadaptations.

PMID- 17010323
TI  - Activation of group II metabotropic glutamate receptors reduces directional
      selectivity in retinal ganglion cells.
AB  - In the mammalian retina, high levels of the group II metabotropic glutamate
      receptor (mGluR) subtype are expressed in starburst amacrine cells. A prominent
      role of starburst amacrine cells is the generation of directional selectivity in
      ON-OFF directionally selective retinal ganglion cells (DS RGCs). Extracellular
      microelectrodes were used to study the effects of activation of group II mGluRs
      on the responses of rabbit ON-OFF DS RGCs to a moving light stimulus.
      Directionally selective responses in these RGCs were substantially reduced by the
      selective group II mGluR agonist DCG-IV. DCG-IV brought out a response to
      movement in the null direction that was similar in magnitude and time course to
      the response to movement in the preferred direction. This effect of DCG-IV was
      reversed by the group II mGluR antagonist EGLU. Application of EGLU alone failed
      to alter directional selectivity in the RGCs but did reduce the response to
      movement in the preferred direction. To determine whether group II mGluRs
      modulate the release of the neurotransmitter acetylcholine from starburst
      amacrine cells, the effect of DCG-IV on ON-OFF DS RGCs was examined in the
      presence of ambenonium, an acetylcholinesterase inhibitor. When applied alone,
      ambenonium greatly prolonged the responses of ON-OFF DS RGCs to a light stimulus.
      This effect of ambenonium was completely abolished upon application of DCG-IV.
      Overall, the results suggest that postsynaptic group II mGluRs have the potential
      to influence directional selectivity in RGCs by inhibiting transmitter release
      from starburst amacrine cells.

PMID- 17010324
TI  - Development of hippocampal alpha7 nicotinic receptors in C3H and DBA/2 congenic
      mice.
AB  - The time course and pattern of development of hippocampal alpha7 nicotinic
      acetylcholine receptors is discernibly different in C3H and DBA/2 mice. In C3H
      mice, the alpha7 receptor is initially expressed on embryonic day 13, exhibits an
      increase in density in area CA1 perinatally and is characterized by a dense,
      diffuse band of alpha-bungarotoxin binding at the CA3/CA1 border in the adult. In
      contrast, the alpha7 receptor is initially expressed on embryonic day 16 in DBA/2
      mice, does not exhibit a transient perinatal increase in binding density in area
      CA1 and is characterized by alpha-bungarotoxin binding to numerous Nissl-stained
      structures in CA1 lacunosum/moleculare in the adult. Currently, it is not known
      whether these developmental differences occur solely as a result of the different
      alleles of the alpha7 receptor gene (Chrna7) expressed by the two strains or
      whether strain-specific background factors also play a role. The present study
      qualitatively examines this question by comparing alpha7 receptor development in
      congenic mice in which the DBA/2 allele of Chrna7 has been introgressed onto a
      C3H genetic background and, conversely, the C3H allele of Chrna7 has been
      introgressed onto a DBA/2 genetic background. The data suggest that hippocampal
      alpha7 receptor development is controlled predominantly by a region of mouse
      chromosome 7 that contains the strain-specific Chrna7 allele.

PMID- 17010325
TI  - Sports or statins for atheroprotection? New insight from Kruppel-like factor 2.

PMID- 17010327
TI  - Chemical process based reconstruction of exposures for an epidemiological study.
      I. Theoretical and methodological issues.
AB  - In the occupational hygiene component of occupational epidemiological studies the
      goal is to assign group average exposure levels that can be used to compute
      individual cumulative exposures. This task requires the availability of
      sufficient amounts of proper individual exposure level data. Typically, the
      required data are either sparse, completely lacking or happenstance data
      collected for purposes not suitable for the aims of the study. In the
      epidemiological study of mortality patterns among industrial workers exposed to
      chloroprene and other substances, we developed and used a process analysis and
      modeling based exposure reconstruction to augment, extrapolate, or interpolate
      the available exposure data. The models developed utilize equations based on the
      engineering principles and chemistry associated with the processes as determined
      from the process documentation and task performance habits as determined from
      interviews of knowledgeable personnel. The resulting equations are tractable and
      provide a general basis for calculating exposure levels for vapors. The
      validation of the results with available exposure measurements suggests that
      comprehensive process analysis and modeling may be used to reconstruct exposures
      or to evaluate exposure potential with scientifically defensible methods.
      Furthermore, even in the absence of validating data, the methodology developed
      has potentially very useful applications in predicting exposure levels to newly
      synthesized substances. Properly interpreted, the limitations of modeling can be
      minimized to obtain scientifically reasonable results.

PMID- 17010326
TI  - Ex vivo activated OVA specific and non-specific CD4+CD25+ regulatory T cells
      exhibit comparable suppression to OVA mediated T cell responses.
AB  - CD4+CD25+ regulatory T cells (Tr) are important in maintaining immune tolerance
      to self-antigen (Ag) and preventing autoimmunity. Reduced number and inadequate
      function of Tr are observed in chronic autoimmune diseases. Adoptively
      transferred Tr effectively suppress ongoing autoimmune disease in multiple animal
      models. Therefore, strategies to modulate Tr have become an attractive approach
      to control autoimmunity. Activation of Tr is necessary for their optimal immune
      regulatory function. However, due to the low ratio of Tr to any given antigen
      (Ag) and the unknown nature of Ag in many autoimmune diseases, specific
      activation is not practical for potential therapeutic intervention. It has been
      shown in animal models that once activated, Tr can exhibit immune suppression in
      a bystander Ag-non-specific fashion, suggesting the effector phase of Tr is Ag
      independent. To investigate whether the immune suppression by activated bystander
      Tr is as potent as that of the Ag specific Tr, Tr cells were isolated from BALB/c
      or ovalbumin (OVA) specific T cell receptor (TCR) transgenic mice (DO11.10) and
      their immune suppression of an OVA specific T cell response was compared. We
      found that once activated ex vivo, Tr from BALB/c and DO11.10 mice exhibited
      comparable inhibition on OVA specific T cell responses as determined by T cell
      proliferation and cytokine production. Furthermore, their immune suppression
      function was compared in a delayed type hypersensitivity (DTH) model induced by
      OVA specific T cells. Again, OVA specific and non-specific Tr exhibited similar
      inhibition of the DTH response. Taken together, the results indicate that ex vivo
      activated Ag-non-specific Tr are as efficient as Ag specific Tr in immune
      suppression, therefore our study provides additional evidence suggesting the
      possibility of applying ex vivo activated Tr therapy for the control of
      autoimmunity.

PMID- 17010328
TI  - The variation of the sarcolipin gene (SLN) in atrial fibrillation, long QT
      syndrome and sudden arrhythmic death syndrome.
AB  - BACKGROUND: Mutations in genes responsible for the cardiac action potential and
      control of intracellular Ca(2+)-distribution are associated with cardiac
      arrhythmia and sudden death. Sarcolipin is a 31-amino acid protein that inhibits
      the sarcoplasmic reticulum Ca(2+) ATPase pump (SERCA2). The sarcolipin gene, SLN,
      is expressed in the heart and a candidate gene for cardiomyopathy as well as
      atrial fibrillation (AF), long QT syndrome (LQTS) or sudden arrhythmic death
      syndrome (SADS). We examined the genetic variation of SLN in patients with the
      arrhythmic disorders AF, LQTS and SADS. METHODS: We screened the coding region of
      SLN for mutations using single strand conformation polymorphism/heteroduplex
      analysis on PCR-amplified genomic DNA from 95 unrelated LQTS patients, 59 SADS
      cases and 147 patients with atrial fibrillation (AF) and 92 controls. Aberrant
      conformers were sequenced. RESULTS: No mutations or polymorphisms were found in
      the coding sequence. A G>C transition in the highly conserved position +1 of the
      3'untranslated region (3'UTR) was found in two SADS cases. A polymorphism, a G>C
      transition at position -65 in the 5'untranslated region (5'UTR), was found with a
      G allele frequency of 0.48. A borderline significant difference in genotype
      distribution of the latter polymorphism was found between the AF group and
      controls. CONCLUSION: Mutations in the coding region of SLN are not frequently
      involved in LQTS, SADS or AF. Whether the described 3'- and 5'UTR variants have
      functional significance must await further studies.

PMID- 17010329
TI  - CRYAB promoter polymorphisms: influence on multiple sclerosis susceptibility and
      clinical presentation.
AB  - BACKGROUND: alphaB-crystallin is a molecular chaperone and potential myelin
      antigen, up-regulated in the earlier stages of multiple sclerosis (MS) lesions.
      In the alphaB-crystallin gene (CRYAB), single nucleotide polymorphisms (SNPs)
      have been associated with MS susceptibility (g.CRYAB-652A>G) and a rapidly
      progressive clinical course (g.CRYAB-650C>G). METHOD: CRYAB was screened for
      mutations in 233 MS patients and 96 controls. Genomic DNA was extracted and the
      coding and 3' and 5' untranslated regions were amplified by PCR. Subsequently,
      the products were analysed by Single Strand Conformation Polymorphism technique
      followed by DNA sequencing of aberrant conformers. RESULTS: In CRYAB (Genbank )
      no mutations were found but SNPs were identified in the promoter region (g.CRYAB
      249C>G, g.CRYAB-650C>G and g.CRYAB-652A>G), and intronic region
      (g.CRYAB.2398T>G). The g.CRYAB-249C>G genotype distribution was significantly
      different between groups (chi(2), p=0.01), caused by differences between
      Relapsing Remitting MS (RRMS) and controls (chi(2), p=0.025) and Secondary
      Progressive MS (SPMS) and controls (chi(2), p=0.05). In addition, a significant
      difference was observed in the g.CRYAB-249C>G allele distribution (chi(2),
      p=0.04), caused by a difference between SPMS and controls (chi(2), p=0.01). In
      RRMS and SPMS a tendency of the g.CRYAB-249GG genotype being associated with an
      earlier age of onset (p=0.05) and a slowly progressive cause (p=0.07) was found.
      Multiple sequence alignment showed conservation of the g.CRYAB-249*C between
      mammalian CRAYB genes and within the small heat shock protein gene family.
      CONCLUSION: CRYAB polymorphisms may be involved in the pathogenesis of MS by
      mechanisms that could involve increased expression of the superantigen alphaB
      crystallin and modulation of the immune response. CRYAB polymorphisms should be
      included in future multivariate biomaker studies in MS.

PMID- 17010330
TI  - Bayesian algorithms for PET image reconstruction with mean curvature and Gauss
      curvature diffusion regularizations.
AB  - The basic mathematical problem behind PET is an inverse problem. Due to the
      inherent ill-posedness of this inverse problem, the reconstructed images will
      have noise and edge artifacts. A roughness penalty is often imposed on the
      solution to control noise and stabilize the solution, but the difficulty is to
      avoid the smoothing of edges. In this paper, we propose two new types of Bayesian
      one-step-late reconstruction approaches which utilize two different prior
      regularizations: the mean curvature (MC) diffusion function and the Gauss
      curvature (GC) diffusion function. As they have been studied in image processing
      for removing noise, these two prior regularizations encourage preserving the edge
      while the reconstructed images are smoothed. Moreover, the GC constraint can
      preserve smaller structures which cannot be preserved by MC. The simulation
      results show that the proposed algorithms outperform the quadratic function and
      total variation approaches in terms of preserving the edges during emission
      reconstruction.

PMID- 17010331
TI  - Suppression of programmed cell death regulates the cyclical degeneration of
      organs in a colonial urochordate.
AB  - The survival of animal tissues and organs is controlled through both activation
      and suppression of programmed cell death. In the colonial urochordate Botryllus
      schlosseri, the entire parental generation of zooids in a colony synchronously
      dies every week as the asexually derived generation of buds reaches functional
      maturity. This process, called takeover, involves massive programmed cell death
      (PCD) of zooid organs via apoptosis followed by programmed removal of cell
      corpses by blood phagocytes within approximately 1 day. We have previously
      reported that developing buds in conjunction with circulating phagocytes are key
      effectors of zooid resorption and macromolecular recycling during takeover, and
      as such engineer the reconstitution of a functional asexual generation every week
      [Lauzon, R.J., Ishizuka, K.J., Weissman, I.L., 2002. Cyclical generation and
      degeneration of organs in a colonial urochordate involves crosstalk between old
      and new: a model for development and regeneration. Dev. Biol. 249, 333-348].
      Here, we demonstrate that zooid lifespan during cyclic blastogenesis is regulated
      by two independent signals: a bud-independent signal that activates zooid PCD and
      a bud-dependent, survival signal that acts in short-range fashion via the
      colonial vasculature. As zooids represent a transient, mass-produced commodity
      during Botryllus asexual development, PCD regulation in this animal via both
      activation and suppression enables it to remove and recycle its constituent
      zooids earlier when intra-colony resources are low, while maintaining the
      functional filter-feeding state when resources are adequate. We propose that this
      crosstalk mechanism between bud and parent optimizes survival of a B. schlosseri
      colony with each round of cyclic blastogenesis.

PMID- 17010332
TI  - The genomic underpinnings of apoptosis in Strongylocentrotus purpuratus.
AB  - Programmed cell death through apoptosis is a pan-metazoan character involving
      intermolecular signaling networks that have undergone substantial lineage
      specific evolution. A survey of apoptosis-related proteins encoded in the sea
      urchin genome provides insight into this evolution while revealing some
      interesting novelties, which we highlight here. First, in addition to a typical
      CARD-carrying Apaf-1 homologue, sea urchins have at least two novel Apaf-1-like
      proteins that are each linked to a death domain, suggesting that echinoderms have
      evolved unique apoptotic signaling pathways. Second, sea urchins have an
      unusually large number of caspases. While the set of effector caspases (caspases
      3/7 and caspase-6) in sea urchins is similar to that found in other basal
      deuterostomes, signal-responsive initiator caspase subfamilies (caspases-8/10 and
      9, which are respectively linked to DED and CARD adaptor domains) have undergone
      echinoderm-specific expansions. In addition, there are two groups of divergent
      caspases, one distantly related to the vertebrate interleukin converting enzyme
      (ICE)-like subfamily, and a large clan that does not cluster with any of the
      vertebrate caspases. Third, the complexity of proteins containing an anti
      apoptotic BIR domain and of Bcl-2 family members approaches that of vertebrates,
      and is greater than that found in protostome model systems such as Drosophila or
      Caenorhabditis elegans. Finally, the presence of Death receptor homologues,
      previously known only in vertebrates, in both Strongylocentrotus purpuratus and
      Nematostella vectensis suggests that this family of apoptotic signaling proteins
      evolved early in animals and was subsequently lost in the nematode and arthropod
      lineage(s). Our results suggest that cell survival is contingent upon a diverse
      array of signals in sea urchins, more comparable in complexity to vertebrates
      than to arthropods or nematodes, but also with unique features that may relate to
      specific requirements imposed by the biphasic life cycle and/or immunological
      idiosyncrasies of this organism.

PMID- 17010333
TI  - Stereospecificity and PAX6 function direct Hoxd4 neural enhancer activity along
      the antero-posterior axis.
AB  - The antero-posterior (AP) and dorso-ventral (DV) patterning of the neural tube is
      controlled in part by HOX and PAX transcription factors, respectively. We have
      reported on a neural enhancer of Hoxd4 that directs expression in the CNS with
      the correct anterior border in the hindbrain. Comparison to the orthologous
      enhancer of zebrafish revealed seven conserved footprints including an obligatory
      retinoic acid response element (RARE), and adjacent sites D, E and F. Whereas
      enhancer function in the embryonic CNS is destroyed by separation of the RARE
      from sites D-E-F by a half turn of DNA, it is rescued by one full turn,
      suggesting stereospecific constraints between DNA-bound retinoid receptors and
      the factor(s) recognizing sites D-E-F. Alterations in the DV trajectory of the
      Hoxd4 anterior expression border following mutation of site D or E implicated
      transcriptional regulators active across the DV axis. We show that PAX6
      specifically binds sites D and E in vitro, and use chromatin immunoprecipitation
      to demonstrate recruitment of PAX6 to the Hoxd4 neural enhancer in mouse embryos.
      Hoxd4 expression throughout the CNS is reduced in Pax6 mutant Sey(Neu) animals on
      embryonic day 8. Additionally, stage-matched zebrafish embryos having decreased
      pax6a and/or pax6b activity display malformed rhombomere boundaries and an
      anteriorized hoxd4a expression border. These results reveal an evolutionarily
      conserved role for Pax6 in AP-restricted expression of vertebrate Hoxd4
      orthologs.

PMID- 17010334
TI  - A Rho-kinase inhibitor, Y-27632, reduces cholinergic contraction but not
      neurotransmitter release.
AB  - This study examined the effects of the selective Rho-kinase inhibitor Y-27632
      [(+)-(R)-trans-4-(1-aminoethyl)-(4-pyridyl)cyclohexanecarboxamide
      dihydrochloride]) on cholinergic nerve-mediated contraction and neurotransmitter
      release in murine and guinea-pig isolated tracheal preparations. In tracheal
      preparations obtained from both species, Y-27632 shifted carbachol concentration
      effect curves to the right and reduced the maximal contractile response. Repeated
      electrical field stimulation (EFS) evoked transient, consistent and reproducible
      contractions in murine and guinea-pig tracheal preparations. Y-27632 inhibited
      these cholinergic nerve-mediated contractions in a concentration-dependent
      manner. EFS (0.1-30 Hz) elicited frequency-dependent cholinergic nerve-mediated
      contractile responses. In murine tracheal preparations, Y-27632 (3 microM and 10
      microM) shifted frequency-response curves to EFS to the right by 5.5 and 13.0
      fold respectively and markedly reduced the maximal contractile response. In
      murine and guinea-pig tracheal preparations loaded with [(3)H]-choline, Y-27632
      (10 microM) significantly increased the EFS-induced outflow of radioactivity from
      airway cholinergic nerves by 27% and 54% respectively. Thus, Y-27632 inhibited
      both carbachol-induced and cholinergic nerve-mediated contractile responses.
      Conversely, Y-27632 increased neurotransmitter release from airway cholinergic
      nerves. However, since antagonism of acetylcholine-induced contraction by Y-27632
      overwhelmed the increased neurotransmitter release, the overall effect of this
      Rho-kinase inhibitor was to inhibit cholinergic nerve-mediated contraction.

PMID- 17010335
TI  - ROCK signaling mediates the adoption of different modes of migration and invasion
      in human mammary epithelial tumor cells.
AB  - For the invasive migration of tumor cells, at least two mechanisms are currently
      discussed: (1) the mesenchymal mode depending on extracellular proteolysis and
      (2) the proteolysis-independent amoeboid mode depending on the activity of the
      Rho kinase ROCK. The ability of tumor cells to switch between different modes of
      motility has been shown to limit the efficiency of agents aimed to reduce
      invasion. Here we show by combining 2D and 3D migration assays that human mammary
      tumor cells exhibited a strongly reduced migration velocity as compared to their
      normal counterparts indicating that high invasiveness is not necessarily
      correlated with high migratory capacity in 2D assays. This reduced migration was
      apparently due to significant differences in actin organization, decreased
      persistence of lamellipodia by 50% and increased cell substrate adhesion. These
      differences resulted from a 2.5-fold higher activity of ROCK and were mediated by
      its downstream effectors myosin light chain kinase and cofilin. Thus, inhibition
      of ROCK activity caused a marked increase in 2D migration efficiency by 40%,
      without, however, affecting 3D invasion. A massive reduction of invasion by 60%
      was achieved by the simultaneous inhibition of the ROCK-dependent amoeboid and
      the extracellular proteolysis-dependent mesenchymal mode. These results may point
      to a new efficient strategy for blocking tumor cell invasion in vivo.

PMID- 17010336
TI  - 2-color photobleaching experiments reveal distinct intracellular dynamics of two
      components of the Hsp90 complex.
AB  - The abundant molecular chaperone Hsp90 functions in association with co
      chaperones including p23 to promote the folding and maturation of a subset of
      cytosolic proteins. "Fluorescence recovery after photobleaching" (FRAP)
      experiments showed that the dynamics of p23 in live cells is dictated by Hsp90.
      Since Hsp90 is present in large excess over p23, the mobility of Hsp90 could
      conceivably be quite different. To facilitate the analysis and to allow a direct
      comparison with p23, we developed a 2-color FRAP technique. Two test proteins are
      expressed as fusion proteins with the two spectrally separable fluorescent
      proteins mCherry and enhanced green fluorescent protein (EGFP). The 2-color FRAP
      technique is powerful for the concomitant recording of two proteins located in
      the same area of a cell, two components of the same protein complex, or mutant
      and wild-type versions of the same protein under identical experimental
      conditions. 2-color FRAP of Hsp90 and p23 is virtually indistinguishable,
      consistent with the notion that they are both engaged in a multitude of large
      protein complexes. However, when Hsp90-p23 complexes are disrupted by the Hsp90
      inhibitor geldanamycin, p23 moves by free diffusion while Hsp90 maintains its low
      mobility because it remains bound in remodeled multicomponent complexes.

PMID- 17010337
TI  - NADPH oxidase-derived ROS: key modulators of heme-induced mitochondrial stability
      in human neutrophils.
AB  - Heme is a proinflammatory molecule able to cause a profound delay of constitutive
      apoptosis of human neutrophils, an effect that likely contributes to chronic
      inflammation associated with hemolytic diseases. Herein we show that heme-induced
      delay of neutrophil apoptosis correlates with the prevention of mitochondrial
      potential (Deltapsi(m)) dissipation by a mechanism dependent on NADPH oxidase
      (NADPHox)-generated reactive oxygen species (ROS) and NF-kappaB. Deltapsi(m)
      maintenance is accompanied by inhibition of Bax insertion into mitochondria and
      by a decrease in the Bad/Bcl-X(L) ratio. Heme induces Bad degradation in a
      completely ROS-dependent manner, as well as Bcl-X(L) synthesis, a phenomenon that
      also requires NF-kappaB activation. These data indicate that heme-induced
      preservation of mitochondrial integrity is a critical checkpoint controlled by
      NADPH oxidase generated-ROS and redox-sensitive NF-kappaB activation.

PMID- 17010338
TI  - Induction by activated macrophage-like THP-1 cells of apoptotic and necrotic cell
      death in intestinal epithelial Caco-2 monolayers via tumor necrosis factor-alpha.
AB  - Intestinal epithelial cells interact with immune cells located in the intestinal
      epithelium via soluble factors. An in vitro model system using coculture was
      constructed to analyze the effect of macrophages on intestinal epithelial cells,
      and human intestinal epithelial-like Caco-2 monolayers and activated macrophage
      like THP-1 cells were used in this study. Coculturing with THP-1 cells resulted
      in an increase of lactate dehydrogenase release from Caco-2 and a decrease in the
      transepithelial electrical resistance of the monolayers, showing that coculturing
      with THP-1 induced cell damage to Caco-2 cells. This disruption was significantly
      suppressed by adding anti-TNF-alpha antibody and etanercept, strongly suggesting
      that TNF-alpha secreted from THP-1 had caused cell damage to Caco-2 monolayers.
      The disrupted Caco-2 monolayers showed both apoptotic and necrotic
      characteristics by morphological and biochemical analyses. TNFRI and NF-kappaB
      seem to have been involved in this regulation. It is suggested that this
      phenomenon is similar in some respects to that observed with IBD and that this in
      vitro coculture system could be a good model for searching for the drugs or food
      substances that can be used to treat or prevent IBD.

PMID- 17010339
TI  - Cannabinoids and neuronal damage: differential effects of THC, AEA and 2-AG on
      activated microglial cells and degenerating neurons in excitotoxically lesioned
      rat organotypic hippocampal slice cultures.
AB  - Cannabinoids (CBs) are attributed neuroprotective effects in vivo. Here, we
      determined the neuroprotective potential of CBs during neuronal damage in
      excitotoxically lesioned organotypic hippocampal slice cultures (OHSCs). OHSCs
      are the best characterized in vitro model to investigate the function of
      microglial cells in neuronal damage since blood-borne monocytes and T-lymphocytes
      are absent and microglial cells represent the only immunocompetent cell type.
      Excitotoxic neuronal damage was induced by NMDA (50 microM) application for 4 h.
      Neuroprotective properties of 9-carboxy-11-nor-delta-9-tetrahydrocannabinol
      (THC), N-arachidonoylethanolamide (AEA) or 2-arachidonoylglycerol (2-AG) in
      different concentrations were determined after co-application with NMDA by
      counting degenerating neurons identified by propidium iodide labeling (PI(+)) and
      microglial cells labeled by isolectin B(4) (IB(4)(+)). All three CBs used
      significantly decreased the number of IB(4)(+) microglial cells in the dentate
      gyrus but the number of PI(+) neurons was reduced only after 2-AG treatment.
      Application of AM630, antagonizing CB2 receptors highly expressed by activated
      microglial cells, did not counteract neuroprotective effects of 2-AG, but
      affected THC-mediated reduction of IB(4)(+) microglial cells. Our results
      indicate that (1) only 2-AG exerts neuroprotective effects in OHSCs; (2)
      reduction of IB(4)(+) microglial cells is not a neuroprotective event per se and
      involves other CB receptors than the CB2 receptor; (3) the discrepancy in the
      neuroprotective effects of CBs observed in vivo and in our in vitro model system
      may underline the functional relevance of invading monocytes and T-lymphocytes
      that are absent in OHSCs.

PMID- 17010340
TI  - Differential regulation of blood-brain barrier permeability in brain trauma and
      pneumococcal meningitis-role of Src kinases.
AB  - Increased vascular permeability causing vasogenic brain edema is characteristic
      for many acute neurological diseases such as stroke, brain trauma, and
      meningitis. Src family kinases, especially c-Src, play an important role in
      regulating blood-brain barrier permeability in response to VEGF, but also mediate
      leukocyte function and cytokine signalling. Here we demonstrate that
      pharmacological inhibition of Src or c-Src deficiency does not influence
      cerebrospinal fluid (CSF) pleocytosis, brain edema formation, and bacterial
      outgrowth during experimental pneumococcal meningitis despite the increased
      cerebral expression of inflammatory chemokines, such as IL-6, CCL-9, CXCL-1, CXCL
      2 and G-CSF as determined by protein array analysis. In contrast, inhibition of
      Src significantly reduced brain edema formation, lesion volume, and clinical
      worsening in cold-induced brain injury without decreasing cytokine/chemokine
      expression. While brain trauma was associated with increased cerebral VEGF
      formation, VEGF levels significantly declined during pneumococcal meningitis.
      Therefore, we conclude that in brain trauma blood-brain barrier tightness is
      regulated by the VEGF/Src pathway whereas c-Src does not influence brain edema
      formation and leukocyte function during bacterial meningitis.

PMID- 17010341
TI  - Mechanism of hypoxia-specific cytotoxicity of procaspase-3 fused with a VHL
      mediated protein destruction motif of HIF-1alpha containing Pro564.
AB  - Under normoxic conditions the alpha-subunit of hypoxia-inducible factor (HIF
      1alpha) protein is targeted for degradation by the von Hippel-Lindau (VHL) tumor
      suppressor protein acting as an E3 ubiquitin ligase. Recently, we developed a
      hypoxia-targeting protein, TOP3, which consisted of procaspase-3 with the VHL
      mediated protein destruction motif of HIF-1alpha. This design enables procaspase
      3 to be regulated similarly with HIF-1alpha, being degraded under normoxia while
      stabilized under hypoxia. Furthermore, stabilized TOP3 was cleaved by the hypoxic
      stress-induced endogenous caspases and thus the procaspase-3 was converted to
      active caspase-3 specifically under hypoxic conditions. These data demonstrated
      that the VHL-mediated protein destruction motif of HIF-1alpha endowed procaspase
      3 with hypoxia-specific cytotoxicity.

PMID- 17010342
TI  - Synthesis of bisphosphonate derivatives of ATP by T4 RNA ligase.
AB  - T4 RNA ligase catalyzes the synthesis of ATP beta,gamma-bisphosphonate analogues,
      using the following substrates with the relative velocity rates indicated between
      brackets: methylenebisphosphonate (pCH(2)p) (100), clodronate (pCCl(2)p) (52),
      and etidronate (pC(OH)(CH(3))p) (4). The presence of pyrophosphatase about
      doubled the rate of these syntheses. Pamidronate (pC(OH)(CH(2)-CH(2)-NH(2))p),
      and alendronate (pC(OH)(CH(2)-CH(2)-CH(2)-NH(2))p) were not substrates of the
      reaction. Clodronate displaced the AMP moiety of the complex E-AMP in a
      concentration dependent manner. The K(m) values and the rate of synthesis
      (k(cat)) determined for the bisphosphonates as substrates of the reaction were,
      respectively: methylenebisphosphonate, 0.26+/-0.05 mM (0.28+/-0.05 s(-1));
      clodronate, 0.54+/-0.14 mM (0.29+/-0.05 s(-1)); and etidronate, 4.3+/-0.5 mM
      (0.028+/-0.013 s(-1)). In the presence of GTP, and ATP or AppCCl(2)p the relative
      rate of synthesis of adenosine 5',5'''-P(1),P(4)-tetraphosphoguanosine (Ap(4)G)
      was around 100% and 33%, respectively; the methylenebisphosphonate derivative of
      ATP (AppCH(2)p) was a very poor substrate for the synthesis of Ap(4)G. To our
      knowledge this report describes, for the first time, the synthesis of ATP
      beta,gamma-bisphosphonate analogues by an enzyme different to the classically
      considered aminoacyl-tRNA synthetases.

PMID- 17010343
TI  - Glucagon-mediated internalization of serine-phosphorylated glucagon receptor and
      Gsalpha in rat liver.
AB  - To assess glucagon receptor compartmentalization and signal transduction in liver
      parenchyma, we have studied the functional relationship between glucagon receptor
      endocytosis, phosphorylation and coupling to the adenylate cyclase system.
      Following administration of a saturating dose of glucagon to rats, a rapid
      internalization of glucagon receptor was observed coincident with its serine
      phosphorylation both at the plasma membrane and within endosomes. Co-incident
      with glucagon receptor endocytosis, a massive internalization of both the 45- and
      47-kDa Gsalpha proteins was also observed. In contrast, no change in the
      subcellular distribution of adenylate cyclase or beta-arrestin 1 and 2 was
      observed. In response to des-His(1)-[Glu(9)]glucagon amide, a glucagon receptor
      antagonist, the extent and rate of glucagon receptor endocytosis and Gsalpha
      shift were markedly reduced compared with wild-type glucagon. However, while the
      glucagon analog exhibited a wild-type affinity for endosomal acidic glucagonase
      activity and was processed at low pH with similar kinetics and rates, its
      proteolysis at neutral pH was 3-fold lower. In response to tetraiodoglucagon, a
      glucagon receptor agonist of enhanced biological potency, glucagon receptor
      endocytosis and Gsalpha shift were of higher magnitude and of longer duration,
      and a marked and prolonged activation of adenylate cyclase both at the plasma
      membrane and in endosomes was observed. The subsequent post-endosomal fate of
      internalized Gsalpha was evaluated in a cell-free rat liver endosome-lysosome
      fusion system following glucagon injection. A sustained endo-lysosomal transfer
      of the two 45- and 47-kDa Gsalpha isoforms was observed. Therefore, these results
      reveal that within hepatic target cells and consequent to glucagon-mediated
      internalization of the serine-phosphorylated glucagon receptor and the Gsalpha
      protein, extended signal transduction may occur in vivo at the locus of the endo
      lysosomal apparatus.

PMID- 17010344
TI  - Jellyfish and other cnidarian envenomations cause pain by affecting TRPV1
      channels.
AB  - Cnidarian envenomations cause a burning-pain sensation of which the underlying
      mechanisms are unknown. Activation of TRPV1, a non-selective cation channel
      expressed in nociceptive neurons, leads to cell depolarisation and pain. Here, we
      show in vitro and in vivo evidence for desensitization-dependent TRPV1 activation
      in cnidarian envenomations. Cnidarian venom induced a nociceptive reactivity,
      comparable to capsaicin, in laboratory rats, which could be reduced by the
      selective TRPV1 antagonist, BCTC. These findings are the first to explain at
      least part of the symptomology of cnidarian envenomations and provide insights
      into the design of more effective treatments for this global public health
      problem.

PMID- 17010345
TI  - A single amino acid mutation attenuates rundown of voltage-gated calcium
      channels.
AB  - The activity of voltage-gated calcium channels (VGCCs) decreases with time in
      whole-cell and inside-out patch-clamp recordings. In this study we found that
      substituting a single amino acid (I1520) at the intracellular end of IIIS6 in the
      alpha(1) subunit of P/Q-type Ca(2+) channels with histidine or aspartate greatly
      attenuated channel rundown in inside-out patch-clamp recordings. The homologous
      mutations also slowed rundown of N- and L-type Ca(2+) channels, albeit to a
      lesser degree. In P/Q-type channels, the attenuation of rundown is accompanied by
      an increased apparent affinity for phosphatidylinositol-4,5-bisphosphate, which
      has been shown to be critical for maintaining Ca(2+) channel activity [L. Wu,
      C.S. Bauer, X.-G. Zhen, C. Xie, J. Yang, Dual regulation of voltage-gated calcium
      channels by PtdIns(4,5)P2. Nature 419 (2002) 947-952]. Furthermore, the histidine
      mutation significantly stabilized the open state, making the channels easier to
      open, slower to close, harder to inactivate and faster to recover from
      inactivation. Our finding that mutation of a single amino acid can greatly
      attenuate rundown provides an easy and efficient way to slow the rundown of
      VGCCs, facilitating functional studies that require direct access to the
      cytoplasmic side of the channel.

PMID- 17010346
TI  - Androgen and the elaborate courtship behavior of a tropical lekking bird.
AB  - In most bird species, male courtship behavior is controlled by testosterone (T)
      and its metabolites. In species breeding in temperate and arctic regions T
      circulates at high levels during a relatively short courtship period because high
      levels of T can be costly in terms of immunocompetence and parental care. Few
      studies have investigated androgen modulation of courtship behavior in tropical
      birds. Male golden-collared manakins (Manacus vitellinus) aggregate in leks for
      several months and perform spectacular, acrobatic courtship displays. Here we
      examined whether T is elevated in golden-collared manakins during the displaying
      period and if courtship behavior is modulated by androgen action on androgen
      receptors. We measured T levels in displaying males at the beginning of the
      breeding season and again, one month later. In addition, both wild and captive
      males were treated with the anti-androgen, flutamide, and their courtship
      behavior was recorded for several weeks. T levels were relatively high shortly
      after leks were established but decreased substantially a month later, even
      though the amount of courtship did not change. Flutamide reduced male courtship
      activity for one week, but display behavior then increased after two weeks of
      flutamide treatment. Our studies show that androgens modulate male manakin
      courtship, but the amount of courtship is not directly correlated with the
      concentration of circulating T. These results suggest that the relationships
      between androgen and courtship might differ between tropical and temperate birds.

PMID- 17010347
TI  - Medical treatment of vulvar squamous cell hyperplasia.
AB  - OBJECTIVE: To evaluate symptomatic response and recurrence rates of graduated
      topical fluorinated corticosteroid in patients with vulvar squamous cell
      hyperplasia. METHODS: Nine hundred seventy-six patients with biopsy-proven vulvar
      squamous cell hyperplasia from 1990 to 2003 were reviewed in this retrospective
      study. All patients were treated with graduated topical fluorinated
      corticosteroid. Data were obtained from hospital records. Symptomatic remission
      and recurrence rates were noted following six months local therapy. RESULTS: The
      mean age was 42.55+/-10.93 (15-85). The remission rate was 93.8% in six months.
      The remission rate was non-significantly higher in postmenopausal patients than
      that in their premenopausal counterpart (94.9% vs 93.0%, p=0.15). The disease
      recurred in 6.9% of patients. Of the patients that suffered recurrence 47.5% had
      persistent disease initially. The patients with following factors older ages (>40
      years), postmenopausal period had significantly higher recurrence rates. Four
      patients with recurrent disease and six patients with persistent disease in the
      form of vulvar intraepithelial neoplasia I-II or atypical squamous hyperplasia,
      were treated with skinning vulvectomy. CONCLUSION: Corticosteroid in the
      treatment of vulvar squamous cell hyperplasia yielded excellent response rates.
      In the evaluation of patients without symptomatic relief, the first step should
      be a vulvar biopsy to exclude the presence of atypical components.

PMID- 17010348
TI  - A risk reduction strategy to prevent maternal deaths associated with unsafe
      abortion.
AB  - INTRODUCTION: Worldwide, 13% of maternal deaths are caused by complications of
      spontaneous or induced abortion, 29% in Uruguay and nearly half (48%) in the
      Pereira Rossell Hospital. PURPOSE: This paper describes a risk reduction strategy
      for unsafe abortions in Montevideo, Uruguay, where over one-fourth of maternal
      deaths are caused by unsafe abortion. METHODS: Although abortion is not legal in
      Uruguay, women desiring abortions can be counseled before and immediately after
      to reduce the risk of injury. Women contemplating abortion were invited to attend
      a "before-abortion" and an "after-abortion" visit at a reproductive health
      polyclinic. At the "before-abortion" visit, gestational age, condition of the
      fetus and pathologies were diagnosed and the risks associated with the use of
      different abortion methods (based on the best available scientific evidence) were
      described. The "after-abortion" visit allowed for checking for possible
      complications and offering contraception. RESULTS: From March 2004 through June
      2005, 675 women attended the "before-abortion" and 495 the "after-abortion"
      visit, the number increasing over time. Some women (3.5%) decided not to abort,
      others were either not pregnant, the fetus/embryo was dead or the woman had a
      condition that permitted legal termination of pregnancy in the hospital (7.5%).
      Most women, however, aborted. All women used vaginal misoprostol in the doses
      recommended in the medical literature. There were no serious complications (one
      mild infection and two hemorrhages not requiring transfusion). CONCLUSION: The
      strategy is effective in reducing unsafe abortions and their health consequences.

PMID- 17010349
TI  - The Women's Role Strain Inventory: a Chinese translation and psychometric
      analyses for Taiwanese women.
AB  - BACKGROUND: To date, there is no instrument that measures role strain experienced
      by Chinese speaking women engaged in multiple roles of working professionals, and
      wife/mother. OBJECTIVES: The objectives of this study were to: (1) translate the
      women's role strain inventory (WRSI) into Chinese; (2) compare the translated
      version (WRSI-C) to the original English version of the instrument to measure
      role strain of women who are engaged in multiple roles; and (3) complete a
      psychometric evaluation of the (WRSI-C) Chinese version of the WRSI in this
      different culture. PARTICIPANTS: Taiwanese women (N=448) working as professional
      nurses, attending classes, and maintaining family responsibilities provided the
      data. METHOD: Reliability of the WRSI-C was compared to the English version by
      comparing Cronbach's alpha coefficients. Test-retest reliability was assessed
      using intra-class and Spearman correlations. Validity of the WRSI-C (long form)
      was assessed using exploratory factor analyses. RESULTS: The WRSI-C was found to
      be both reliable and valid. CONCLUSIONS: The reliability and validity of the WRSI
      C appeared to be consistent across English and Taiwanese samples.

PMID- 17010350
TI  - Paraphyly of the Pseudophyllidea (Platyhelminthes: Cestoda): circumscription of
      monophyletic clades based on phylogenetic analysis of ribosomal RNA.
AB  - Phylogenetic relationships of cestodes of the order Pseudophyllidea
      (Platyhelminthes: Cestoda) were examined using sequences of complete small
      subunit and partial (D1-D3 region) large subunit nuclear rDNA of members of all
      pseudophyllidean families. The results provide evidence of paraphyly of the order
      as indicated by previous molecular phylogenetic analyses based on a much lower
      number of species sequenced. Pseudophyllidean tapeworms represent an artificial
      assemblage comprising two unrelated clades. "Bothriocephalidea" is formed by four
      families sensu Bray et al. (1994), namely Bothriocephalidae, Echinophallidae,
      Philobythiidae and Triaenophoridae, whereas two other families,
      Diphyllobothriidae and Cephalochlamydidae, give rise to the "Diphyllobothriidea".
      The present results indicate that "Bothriocephalidea" forms the most derived
      clade of all difossate and tetrafossate/bothriate tapeworm lineages which are
      considered to be basal relative to the rest of tetrafossate/bothridiate and
      acetabulate cestodes. By contrast, "Diphyllobothriidea", which includes medically
      important parasites (Diphyllobothrium and Spirometra), appeared more basal,
      without a clearly resolved position within other difossate tapeworm lineages.

PMID- 17010351
TI  - c-Reactive protein and the metabolic syndrome in older Chinese: Guangzhou Biobank
      Cohort Study.
AB  - OBJECTIVE: To examine the association between serum c-reactive protein (CRP)
      concentration and the metabolic syndrome (MS) using the International Diabetes
      Federation Metabolic Syndrome Guidelines (April, 2005) definition in an older
      Chinese population. METHODS: Three thousand and fourteen men and 7275 women aged
      50-85 years were recruited and received a full medical check-up including
      measurement of blood pressure, obesity indices, fasting total, LDL-, HDL
      cholesterol, triglycerides, glucose and c-reactive protein. Data describing
      socioeconomic and lifestyle factors was also collected. RESULTS: Vascular risk
      factors including waist circumference, weight gain and waist gain since the age
      of 18, body mass index, waist-hip-ratio, triglyceride, HDL-cholesterol, and
      systolic and diastolic blood pressures were positively associated with CRP in
      both men and women (p from <0.001 to 0.016). Compared to those without MS
      components, adjusted odds ratios for having elevated CRP increased in those with
      the MS or its components compared those without MS or components (all p<0.001),
      except for the low HDL-cholesterol in both genders and raised fasting glucose in
      men. Similarly, the risk of elevated CRP increased with escalating MS components
      even after adjustment of a range of potential confounders. CONCLUSIONS: There is
      a strong relationship between CRP and the constellation of MS components and
      associated vascular risk in this older Chinese population.

PMID- 17010352
TI  - Determination of retention indices in constant inlet pressure mode and conversion
      among different column temperature conditions in comprehensive two-dimensional
      gas chromatography.
AB  - A method to determine the second dimensional real retention time, dead times on
      both dimensions and retention indices in constant inlet pressure mode was
      developed in comprehensive two-dimensional gas chromatography. At the same time,
      the conversion of GC x GC retention indices among different column temperature
      conditions were also conducted based on some thermodynamics parameters. The
      calculation accuracies are better than 1.0 retention index unit. Furthermore, a
      retention index database was developed and used to identify the compounds in a
      cigarette essential oil sample. It showed that identification by the database was
      of close agreement with by time-of-flight mass spectrometry, and some isomers
      could also be distinguished based on the retention index database.

PMID- 17010353
TI  - Evaluation of solid adsorbent materials for cryogen-free trapping-gas
      chromatographic analysis of atmospheric C2-C6 non-methane hydrocarbons.
AB  - Nine commercial solid adsorbent materials (in order of decreasing surface area:
      Carboxen 1000, Carbosieve S III, molecular sieve 5A, molecular sieve 4A, silica
      gel, Carboxen 563, activated alumina, Carbotrap and Carboxen 1016) were
      investigated for their ability to trap and release C2-C6 non-methane hydrocarbons
      (NMHCs) in atmospheric samples for subsequent thermal desorption gas
      chromatography-flame ionization detection analysis (GC-FID). Recovery rates for
      23 NMHCs and methyl chloride (CH3Cl) were determined. A microtrap filled with the
      three adsorbents Carbosieve S III, Carboxen 563 and Carboxen 1016 was found to
      allow for the analysis of the widest range of target analytes. A detection limit
      of approximately 3pptC [parts per trillion (carbon)] in a 1l air sample and a
      linear response over a wide range of volatilities and sample volumes was
      determined for this configuration. Water vapor in the sample air was found to
      causes interference in trapping and subsequent chromatographic analysis of light
      NMHCs. A Peltier-cooled, regenerable water trap inserted into the sample flow
      path was found to mitigate these problems and to allow quantitative and
      reproducible results for all analytes at all tested humidity conditions.

PMID- 17010354
TI  - Isolation and seasonal effects on characteristics of fulvic acid isolated from an
      Australian floodplain river and billabong.
AB  - Fulvic acids from an Australian floodplain river and billabong were isolated
      using DEAE and DAX-8 resins, and characterised with the use of size exclusion
      chromatography and solid-state CP-MAS (13)C NMR spectroscopy. Differences between
      the two resin isolates were evident. Fulvic acids isolated using DEAE-cellulose
      had higher apparent M(n) and M(w) values, while the DAX-8 resin showed a slight
      preference for aliphatic components. Fulvic acids from the river and billabong
      had the same functional groups present, however, the river fulvic acids had
      higher apparent M(n) (number average molecular weight) and M(w) values (weight
      average molecular weight), and were more polydisperse than the billabong fulvic
      acid. There were no significant changes in the characteristics of the fulvic acid
      isolated from the river at four sampling times: summer, autumn, winter and
      spring. In contrast, fulvic acids isolated from a billabong displayed seasonal
      variation in molecular weights. This work emphasizes the importance in ecological
      studies of isolation procedure for the operationally defined fulvic acids.

PMID- 17010355
TI  - Analysis of 5-hydroxymethylfurfural in foods by gas chromatography-mass
      spectrometry.
AB  - A new, simple and selective method for the analysis of 5-hydroxymethylfurfural
      (HMF) in foods by gas chromatography coupled to mass spectrometry (GC-MS) is
      proposed. Several derivatising procedures based on the formation of an HMF
      silylated derivative using different reagents were studied. Among the
      derivatising reagents examined, N,O-bis-trimethylsilyltrifluoroacetamide (BSTFA)
      provided the best derivatisation yield. Sample clean-up was also optimised, using
      either liquid-liquid extraction with dichloromethane or solid-phase extraction
      (SPE) with several commercially available cartridges, and the best results were
      obtained using ENV+ cartridges. Quality parameters such as day-to-day and run-to
      run precision (RSD<10%), linearity (between 25 and 700 ng g(-1)) and detection
      limit (6 ng g(-1)) were established. This method was successfully applied to the
      analysis of HMF content in several Spanish food samples from a local market, such
      as jam, honey, orange juice and bakery products.

PMID- 17010356
TI  - Molecularly imprinted polymers for solid-phase extraction and solid-phase
      microextraction: recent developments and future trends.
AB  - Molecularly imprinted polymers (MIPs) are synthetic polymers having a
      predetermined selectivity for a given analyte, or group of structurally related
      compounds, that make them ideal materials to be used in separation processes. In
      this sense, during past years a huge amount of papers have been published dealing
      with the use of MIPs as sorbents in solid-phase extraction, namely molecularly
      imprinted solid-phase extraction (MISPE). Although the majority of these papers
      were restricted to describe the use of different templates for different
      applications, several attempts proposing new alternatives to minimize the
      inherent drawbacks of the preparation and use of MIPs (i.e. template bleeding,
      tedious synthesis procedure, etc.) have been reported. Thus, this paper does not
      pretend to be a collection of MISPE-related papers but to give an overview on the
      significant attempts carried out during recent years to improve the performance
      of MIPs in solid-phase extraction. In addition, the use of MIPs packed in high
      performance liquid chromatography (HPLC) columns for the direct injection of
      crude sample extracts and the preparation of imprinted fibres for solid-phase
      microextraction will be also discussed.

PMID- 17010357
TI  - Surface modification of hydroxyapatite nanocrystals by grafting polymers
      containing phosphonic acid groups.
AB  - A novel approach for the surface modification of hydroxyapatite (HAp)
      nanocrystals is described by grafting polymerization of vinyl phosphonic acid
      (VPA) using a redox initiating system in an aqueous media. Fourier transform
      infrared (FT-IR) and XRD analyses confirmed the modification reaction on HAp
      surfaces. Inductively coupled plasma mass spectroscopy (ICP MS) showed that the
      Ca/P molar ratio decreased from 1.67 to 1.36 with increasing the feed VPA amount.
      Zeta potentials of unmodified HAp and modified HAp in phosphate-buffered saline
      (PBS) solutions (pH 7.4, ionic strength = 10 mM) were negative and decreased with
      increasing the amount of grafted PVPA. Transmission electron microscopy (TEM)
      measurements and time-dependent phase monitoring indicated that the colloidal
      stability of modified HAp over unmodified HAp in water dramatically increased and
      tended to exist as single nanocrystals without aggregation.

PMID- 17010358
TI  - Adhesion as an interplay between particle size and surface roughness.
AB  - Surface roughness plays an important role in the adhesion of small particles. In
      this paper we have investigated adhesion as a geometrical effect taking into
      account both the particle size and the size of the surface features. Adhesion is
      studied using blunt model particles on surfaces up to 10 nm root-mean-square
      (RMS) roughness. Measurements with particles both smaller and larger than surface
      features are presented. Results indicate different behavior in these areas.
      Adhesion of particles smaller than or similar in size to the asperities depend
      mainly on the size and shape of the asperities and only weakly on the size of the
      particle. For large particles also the particle size has a significant effect on
      the adhesion. A new model, which takes the relative size of particles and
      asperities into account, is also derived and compared to the experimental data.
      The proposed model predicts adhesion well over a wide range of particle/asperity
      length scales.

PMID- 17010359
TI  - Experimental humidity dependency of small particle adhesion on silica and
      titania.
AB  - The humidity present in ambient atmosphere affects the adhesion of small
      particles by causing capillary bridge formation between the particle and the
      surface. Even in moderate relative humidities this, usually attractive, force can
      have a significant effect on adhesion behaviour of micro and sub-micro particles.
      We have directly measured the pull-off forces of initially adhered oxide
      particles on oxide surfaces with atomic force microscope in controlled atmosphere
      with adjustable humidity. We demonstrate the effect of the surface roughness
      resulting in two different regions of capillary formation and the particle shape
      having a strong effect on the humidity dependency of adhesion. The experimental
      results are explained by theoretical framework.

PMID- 17010360
TI  - Thermosensitive-polymer-coated magnetic nanoparticles: adsorption and desorption
      of bovine serum albumin.
AB  - Adsorption and desorption behavior of Bovine Serum Albumin (BSA) on surface
      modified magnetic nanoparticles covered with thermosensitive polymer (PNIPAM) was
      investigated as a function of temperature, pH, and ionic strength.
      Functionalization of surface-modified magnetic particles was performed by seed
      polymerization using N-isopropylacrylamide (PNIPAM) as the main monomer.
      Characterization of these particles was carried out using transmission electron
      micrography (TEM), and vibrating sample magnetometry (VSM). The adsorption
      results exhibited both pH and temperature sensitivity. The results showed that
      the temperature effect on adsorption/desorption behavior was mainly dependent on
      the properties of the particles' surface. The effect of pH was also investigated
      and it was observed that a smaller amount of protein was adsorbed at higher pH
      because of the electrostatic repulsive force between protein molecules and latex
      particles. The maximum amount of protein was adsorbed near the isoelectric point
      of BSA. Desorption results showed that more protein was desorbed when adsorption
      was done at lower temperatures and desorption efficiency was found to be higher
      than 80%.

PMID- 17010361
TI  - Fabrication of hollow multifunctional spheres containing MCM-41 nanoparticles and
      magnetite nanoparticles using layer-by-layer method.
AB  - Macroscopic mesoporous silica spheres have been fabricated by alternatively
      depositing preformed MCM-41 nanoparticles and polyelectrolytes onto polystyrene
      lattices. High surface area hollow mesoporous spheres were obtained by removal of
      the core by solvent or calcination. Further, the versatility of the layer-by
      layer (LBL) method was extended to fabricate magnetite-mesoporous silica
      composites by depositing magnetite and MCM-41 nanoparticles onto polystyrene
      beads. Such high surface area composites are important since the mesopores can be
      used for encapsulation of varied materials like enzymes and drugs while the
      presence of magnetite ensures application in biocatalysis and separation under
      magnetic field.

PMID- 17010362
TI  - A control over accessibility of immobilized enzymes through porous coating layer.
AB  - We report immobilization of an enzyme by layer-by-layer (LbL) film deposition
      technique. All the enzyme layers, including the inner ones, contributed to the
      activity. We put-forwarded additional coating layers to protect the enzymes. To
      control the accessibility of the enzymes beneath the coating layer, pores have
      been introduced. Our results show controlled accessibility of immobilized enzymes
      in solid-state matrices.

PMID- 17010363
TI  - Solubility measurement of methane in aqueous solution of sodium dodecyl sulfate
      at ambient temperature and near hydrate conditions.
AB  - Solubility data of methane in aqueous solutions of sodium dodecyl sulfate (SDS)
      with different concentrations were measured at ambient temperature and near
      hydrate conditions. The critical micelle concentration (CMC) and the number of
      methane molecules dissolved in each micelle of the methane + water + SDS system
      were calculated and compared with those of the ethylene + water + SDS system. The
      results demonstrated that the micelles could be formed in the SDS concentration
      range where an efficient promotion effect on hydrate formation was previously
      reported; the micelle solubilization to methane molecules was remarkable near
      hydrate conditions, and the ethylene molecules could be solubilized in micelles
      in preference to methane molecules.

PMID- 17010364
TI  - Cloud point extraction and graphite furnace atomic absorption spectrometry
      determination of manganese(II) and iron(III) in water samples.
AB  - Cloud point extraction (CPE) was applied as a preconcentration step prior to
      graphite furnace atomic absorption spectrometry (GFAAS) determination of
      manganese(II) and iron(III) in water samples. After complexation with 1-phenyl-3
      methyl-4-benzoyl-5-pyrazolone (PMBP), the analytes could be quantitatively
      extracted to the phase rich in the surfactant p
      octylpolyethyleneglycolphenylether (Triton X-100) and be concentrated, then
      determined by GFAAS. The parameters affecting the extraction efficiency, such as
      solution pH, concentration of PMBP and Triton X-100, equilibration temperature
      and time, were investigated in detail. Under the optimum conditions,
      preconcentration of 10 ml of sample solution permitted the detection of 0.02 ng
      ml(-1) of Mn(II) and 0.08 ng ml(-1) of Fe(III) with enrichment factors of 31 and
      25 for Mn(II) and Fe(III), respectively. The proposed method was applied to
      determination of trace manganese(II) and iron(III) in water samples with
      satisfactory results.

PMID- 17010365
TI  - Reproducibility of the T-wave alternans and dependence of T-wave alternans on the
      T-wave amplitude: 2 issues requiring immediate attention.

PMID- 17010366
TI  - A technician's guide for basic ECG analysis. Technical suggestions for reducing
      baseline artifact in ECG recordings.

PMID- 17010367
TI  - Individual mouse analysis of the cellular immune response to tumor antigens in
      peripheral blood by intracellular staining for cytokines.
AB  - Among the experimental animal models, mice remain the most widely used for the
      evaluation of immunotherapeutic strategies. Vaccines against parasites and viral
      antigens are commonly administered to the appropriate mouse strain which also
      allows testing of the therapeutic effect. Similarly, in mice transgenic for human
      tumor associated antigens (TAA), cancer vaccines must lead to breakage of immune
      tolerance to elicit a significant effect on the tumor. However, one of the major
      drawbacks in the monitoring of cellular immune responses induced by vaccination
      is that functional immunological assays require suppression of the animals to
      collect the spleen or lymph nodes for analysis. Here, we report the application
      of a rapid intracellular staining (ICS) method to quantify antigen-specific T
      cells responses in small volumes of murine blood. Genetic vaccination with
      plasmid DNA followed by electroporation (DNA-EP) and the use of adenoviral
      vectors (Ad) encoding CEA as a model target antigen were applied to different
      strains of mice. Optimal blood volume, number of lymphocytes, sensitivity and
      reproducibility of intracellular staining for IFN-gamma were determined both in
      non-tolerant/wild type mice as well as in tolerant CEA transgenic mice upon
      restimulation of PBMCs with CEA peptides. Groups of vaccinated mice were then
      sacrificed and PBMCs and splenocytes from individual animals were compared for
      intracytoplasmic detection of IFN-gamma and TNF-alpha. A significant correlation
      was observed between splenic and blood immune responses. Finally, the cellular
      immune response was followed over time in groups of vaccinated mice. The kinetics
      of IFN-gamma producing effectors were measured after priming and successive
      boosting with adenoviral vectors. We show that intracellular staining for mouse
      PBMCs is a rapid and simple method to measure antigen-specific immune responses.
      It does not require animal euthanasia and mirrors the response observed in
      lymphoid organs such as the spleen.

PMID- 17010368
TI  - The automated counting of spots for the ELISpot assay.
AB  - An automated method for counting spot-forming units in the ELISpot assay is
      described that uses a statistical model fit to training data that is based on
      counts from one or more experts. The method adapts to variable background
      intensities and provides considerable flexibility with respect to what image
      features can be used to model expert counts. Point estimates of spot counts are
      produced together with intervals that reflect the degree of uncertainty in the
      count. Finally, the approach is completely transparent and "open source" in
      contrast to methods embedded in current commercial software. An illustrative
      application to data from a study of the reactivity of T-cells from healthy human
      subjects to a pool of immunodominant peptides from CMV, EBV and flu is presented.

PMID- 17010369
TI  - Development of an in vitro potency assay for therapeutic TGFbeta antagonists: the
      A549 cell bioassay.
AB  - A bioassay was developed to assess the potency of TGFbeta antagonists by
      measuring IL-11 production in TGFbeta-1 treated human lung epithelial cells
      (A549). The production of IL-11 by A549 cells, measured by ELISA, was shown to be
      proportional to the TGFbeta-1 concentration. The A549 cells were responsive to
      all three isoforms of TGFbeta in the range of 3.0 ng/mL to 1.4 pg/mL, with an 18
      to 24 h exposure time found to be within the linear portion of the bioassay
      response range. The Effective Dose at 80% of the maximal response (ED80) of
      TGFbeta-1 determined for the assay was 0.3 ng/mL. With this level of TGFbeta-1, a
      human anti-TGFbeta-1 antibody (CAT-192) yielded an approximate median Inhibitory
      Concentration (IC50) value of 3 microg/mL. To investigate assay specificity,
      alternate members of the TGFbeta superfamily were evaluated. Recombinant human
      activin B, inhibin A and BMP-2 (Bone Morphogenetic Protein-2) did not elicit a
      significant IL-11 response from the A549 cell line. Bioassay qualification was
      performed to obtain estimates of precision and accuracy, as well as to establish
      plate validity criteria. Assay precision was estimated at 30%, while the accuracy
      was +/-13%. Additionally, the ability of the A549 cell potency assay to detect
      potency differences in structurally modified samples was investigated.

PMID- 17010370
TI  - Rapid and efficient identification of epitopes/mimotopes from random peptide
      libraries.
AB  - Phage-displayed random peptide libraries are important tools in identifying novel
      epitopes/mimotopes that may lead to the determination of antigen specificity. In
      this approach, high-affinity phage peptides are enriched by affinity selection
      (panning) on a monoclonal antibody. To facilitate identification of all potential
      phage peptides specific for recombinant monoclonal antibodies (rAbs) previously
      generated from clonally expanded plasma cells from the cerebrospinal fluid of
      patients with multiple sclerosis (MS), we developed a high-throughput method to
      determine phage specificity. In contrast to the 8-9 days needed in the standard
      large-scale method of amplifying phage clones for ELISA, the high-throughput
      method takes only 1 day. ELISA using phage clones amplified directly in 96-well
      plates avoids large-scale phage purification and enables rapid identification of
      specific epitopes/mimotopes. This technique will expedite identification of MS
      specific peptides that can be used to discover the corresponding protein
      antigens.

PMID- 17010371
TI  - Development of a multiplexed fluorescent immunoassay for the quantitation of
      antibody responses to group A streptococci.
AB  - The host immunologic response to group A streptococcal infections gives rise to
      numerous antibodies directed against cellular and extracellular bacterial
      antigens. For determining individual immune status, or studying the pathogenesis
      of group A streptococcal associated diseases, such as acute rheumatic fever
      (ARF), an assay capable of determining antibodies responses to multiple antigens
      would be of great advantage. We have developed a microsphere based, multiplexed
      immunoassay for the simultaneous quantitation of antibodies to nine different
      extracellular, ARF related tissue and group A streptococci specific antigens
      using only 5 microl of sample. Through the selection of microspheres and serum
      diluent, non-specific antibody binding was reduced by 17%. Different formulations
      of the coupling buffer were found to greatly influence the efficiency of coupling
      antigens to the carboxylated microspheres. Monoclonal antibodies against the
      different antigens demonstrated assay specificity as well as sensitivities of
      less than 1 ng/ml of antibody. This multiplexed assay should be a powerful
      research and clinical tool in determining antibody responses to group A
      streptococcal infections and in potentially determining the role of a variety of
      cross-reactive antigens in rheumatic fever and rheumatic heart disease.

PMID- 17010372
TI  - CXCR4 modulates contractility in adult cardiac myocytes.
AB  - The inflammatory response is critical to the development and progression of heart
      failure. Chemokines and their receptors are a distinct class of inflammatory
      modulators that may play a role in mediating myocardial dysfunction in heart
      failure. Levels of the chemokine CXCL12, also known as stromal cell-derived
      factor (SDF), and its receptor, CXCR4, are elevated in patients with heart
      failure, and we undertook this study to determine whether this chemokine system
      can directly affect cardiac function in the absence of leukocytes. Murine
      papillary muscles and adult rat cardiac myocytes treated with CXCL12, the only
      identified ligand of CXCR4, demonstrate blunted inotropic responses to
      physiologic concentrations of calcium. The negative inotropic effects on cardiac
      myocytes are accompanied by a proportional diminution of calcium transients. The
      effects are abrogated by AMD3100, a specific CXCR4 inhibitor. Overexpression of
      the receptor through adenoviral infection with a CXCR4 construct accentuates the
      negative inotropic effects of CXCL12 on cardiac myocytes during calcium
      stimulation. CXCR4 activation also attenuates beta-adrenergic-mediated increases
      in calcium mobilization and fractional shortening in cardiac myocytes. In
      electrophysiologic studies, CXCL12 decreases forskolin- and isoproterenol-induced
      voltage-gated L-type calcium channel activation. These studies demonstrate that
      activation of CXCR4 results in a direct negative inotropic modulation of cardiac
      myocyte function. The specific mechanism of action involves alterations of
      calcium channel activity on the membrane. The presence of functional CXCR4 on
      cardiac myocytes introduces a new target for treating cardiac dysfunction.

PMID- 17010374
TI  - Localization of prefoldin interaction sites in the hyperthermophilic group II
      chaperonin and correlations between binding rate and protein transfer rate.
AB  - Prefoldin is a molecular chaperone that captures a protein-folding intermediate
      and transfers it to a group II chaperonin for correct folding. The manner by
      which prefoldin interacts with a group II chaperonin is poorly understood. Here,
      we have examined the prefoldin interaction site in the archaeal group II
      chaperonin, comparing the interaction of two Thermococcus chaperonins and their
      mutants with Pyrococcus prefoldin by surface plasmon resonance. We show that the
      mutations of Lys250 and Lys256 of Thermococcus alpha chaperonin residues to Glu
      residues increase the affinity to Pyrococcus prefoldin to the level of
      Thermococcus beta chaperonin and Pyrococcus chaperonin, indicating that their
      Glu250 and Glu256 residues of the helical protrusion region are responsible for
      relatively stronger binding to Pyrococcus prefoldin than Thermococcus alpha
      chaperonin. Since the putative chaperonin binding sites in the distal ends of
      Pyrococcus prefoldin are rich in basic residues, electrostatic interaction seems
      to be important for their interaction. The substrate protein transfer rate from
      prefoldin correlates well with its affinity for chaperonin.

PMID- 17010373
TI  - Substrate recognition, protein dynamics, and iron-sulfur cluster in Pseudomonas
      aeruginosa adenosine 5'-phosphosulfate reductase.
AB  - APS reductase catalyzes the first committed step of reductive sulfate
      assimilation in pathogenic bacteria, including Mycobacterium tuberculosis, and is
      a promising target for drug development. We report the 2.7 A resolution crystal
      structure of Pseudomonas aeruginosa APS reductase in the thiosulfonate
      intermediate form of the catalytic cycle and with substrate bound. The structure,
      high-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass
      spectrometry, and quantitative kinetic analysis, establish that the two
      chemically discrete steps of the overall reaction take place at distinct sites on
      the enzyme, mediated via conformational flexibility of the C-terminal 18
      residues. The results address the mechanism by which sulfonucleotide reductases
      protect the covalent but labile enzyme-intermediate before release of sulfite by
      the protein cofactor thioredoxin. P. aeruginosa APS reductase contains an [4Fe
      4S] cluster that is essential for catalysis. The structure reveals an unusual
      mode of cluster coordination by tandem cysteine residues and suggests how this
      arrangement might facilitate conformational change and cluster interaction with
      the substrate. Assimilatory 3'-phosphoadenosine 5'-phosphosulfate (PAPS)
      reductases are evolutionarily related, homologous enzymes that catalyze the same
      overall reaction, but do so in the absence of an [Fe-S] cluster. The APS
      reductase structure reveals adaptive use of a phosphate-binding loop for
      recognition of the APS O3' hydroxyl group, or the PAPS 3'-phosphate group.

PMID- 17010375
TI  - Structures of human N-Acetylglucosamine kinase in two complexes with N
      Acetylglucosamine and with ADP/glucose: insights into substrate specificity and
      regulation.
AB  - N-Acetylglucosamine (GlcNAc), a major component of complex carbohydrates, is
      synthesized de novo or salvaged from lysosomally degraded glycoconjugates and
      from nutritional sources. The salvage pathway requires that GlcNAc kinase
      converts GlcNAc to GlcNAc-6-phosphate, a component utilized in UDP-GlcNAc
      biosynthesis or energy metabolism. GlcNAc kinase belongs to the sugar
      kinase/Hsp70/actin superfamily that catalyze phosphoryl transfer from ATP to
      their respective substrates, and in most cases catalysis is associated with a
      large conformational change in which the N-terminal small and C-terminal large
      domains enclose the substrates. Here we report two crystal structures of
      homodimeric human GlcNAc kinase, one in complex with GlcNAc and the other in
      complex with ADP and glucose. The active site of GlcNAc kinase is located in a
      deep cleft between the two domains of the V-shaped monomer. The enzyme adopts a
      "closed" configuration in the GlcNAc-bound complex and GlcNAc interacts with
      residues of both domains. In addition, the N-acetyl methyl group contacts
      residues of the other monomer in the homodimer, a unique feature compared to
      other members of the sugar kinase/Hsp70/actin superfamily. This contrasts an
      "open" configuration in the ADP/glucose-bound structure, where glucose cannot
      form these interactions, explaining its low binding affinity for GlcNAc kinase.
      Our results support functional implications derived from apo crystal structures
      of GlcNAc kinases from Chromobacter violaceum and Porphyromonas gingivalis and
      show that Tyr205, which is phosphorylated in thrombin-activated platelets, lines
      the GlcNAc binding pocket. This suggests that phosphorylation of Tyr205 may
      modulate GlcNAc kinase activity and/or specificity.

PMID- 17010376
TI  - The 1.7 A crystal structure of Dronpa: a photoswitchable green fluorescent
      protein.
AB  - The green fluorescent protein (GFP), its variants, and the closely related GFP
      like proteins possess a wide variety of spectral properties that are of
      widespread interest as biological tools. One desirable spectral property, termed
      photoswitching, involves the light-induced alteration of the optical properties
      of certain GFP members. Although the structural basis of both reversible and
      irreversible photoswitching events have begun to be unraveled, the mechanisms
      resulting in reversible photoswitching are less clear. A novel GFP-like protein,
      Dronpa, was identified to have remarkable light-induced photoswitching
      properties, maintaining an almost perfect reversible photochromic behavior with a
      high fluorescence to dark state ratio. We have crystallized and subsequently
      determined to 1.7 A resolution the crystal structure of the fluorescent state of
      Dronpa. The chromophore was observed to be in its anionic form, adopting a cis co
      planar conformation. Comparative structural analysis of non-photoactivatable and
      photoactivatable GFPs, together with site-directed mutagenesis of a position
      (Cys62) within the Dronpa chromophore, has provided a basis for understanding
      Dronpa photoactivation. Specifically, we propose a model of reversible
      photoactivation whereby irradiation with light leads to subtle conformational
      changes within and around the environment of the chromophore that promotes proton
      transfer along an intricate polar network.

PMID- 17010377
TI  - Ddi1, a eukaryotic protein with the retroviral protease fold.
AB  - Retroviral aspartyl proteases are homodimeric, whereas eukaryotic aspartyl
      proteases tend to be large, monomeric enzymes with 2-fold internal symmetry. It
      has been proposed that contemporary monomeric aspartyl proteases evolved by gene
      duplication and fusion from a primordial homodimeric enzyme. Recent sequence
      analyses have suggested that such "fossil" dimeric aspartyl proteases are still
      encoded in the eukaryotic genome. We present evidence for retention of a dimeric
      aspartyl protease in eukaryotes. The X-ray crystal structure of a domain of the
      Saccharomyces cerevisiae protein Ddi1 shows that it is a dimer with a fold
      similar to that of the retroviral proteases. Furthermore, the double Asp-Thr-Gly
      Ala amino acid sequence motif at the active site of HIV protease is found with
      identical geometry in the Ddi1 structure. However, the putative substrate binding
      groove is wider in Ddi1 than in the retroviral proteases, suggesting that Ddi1
      accommodates bulkier substrates. Ddi1 belongs to a family of proteins known as
      the ubiquitin receptors, which have in common the ability to bind ubiquitinated
      substrates and the proteasome. Ubiquitin receptors contain an amino-terminal
      ubiquitin-like (UBL) domain and a carboxy-terminal ubiquitin-associated (UBA)
      domain, but Ddi1 is the only representative in which the UBL and UBA domains
      flank an aspartyl protease-like domain. The remarkable structural similarity
      between the central domain of Ddi1 and the retroviral proteases, in the global
      fold and in active-site detail, suggests that Ddi1 functions proteolytically
      during regulated protein turnover in the cell.

PMID- 17010378
TI  - Identification of Escherichia coli m2G methyltransferases: I. the ycbY gene
      encodes a methyltransferase specific for G2445 of the 23 S rRNA.
AB  - N2-methylguanosine 2445 of the 23 S rRNA is located in a cluster of modified
      nucleotides concentrated at the peptidyl transferase center of the ribosome. Here
      we describe the identification of a gene, ycbY, as encoding an enzyme responsible
      for methylation of G2445. Knock-out of the ycbY gene leads to loss of
      modification at G2445 as revealed by reverse transcription. The modification is
      restored in the ycbY knock-out strain if co-transformed with a plasmid expressing
      the ycbY gene product. Recombinant YcbY protein is able to methylate 23 S rRNA
      purified from the ycbY knock-out strain in vitro, assembled 50 S subunits are not
      a substrate for the methylase. Knock-out of the ycbY gene leads to growth
      retardation. Growth competition with the parental wild-type strain leads to a
      gradual decrease in the knock-out strain cells proportion in the media. It is
      likely that the G2445 modification is necessary for prevention of non-functional
      secondary or tertiary structure formation at the peptidyl transferase center.
      Based on these results we suggest that YcbY be renamed to RlmL in accordance with
      the accepted nomenclature for rRNA methyltransferases.

PMID- 17010379
TI  - Structural basis of the sulphate starvation response in E. coli: crystal
      structure and mutational analysis of the cofactor-binding domain of the Cbl
      transcriptional regulator.
AB  - Cbl is a member of the large family of LysR-type transcriptional regulators
      (LTTRs) common in bacteria and found also in Archaea and algal chloroplasts. The
      function of Cbl is required in Escherichia coli for expression of sulphate
      starvation-inducible (ssi) genes, associated with the biosynthesis of cysteine
      from organic sulphur sources (sulphonates). Here, we report the crystal structure
      of the cofactor-binding domain of Cbl (c-Cbl) from E. coli. The overall fold of c
      Cbl is very similar to the regulatory domain (RD) of another LysR family member,
      CysB. The RD is composed of two subdomains enclosing a cavity, which is expected
      to bind effector molecules. We have constructed and analysed several full-length
      Cbl variants bearing single residue substitutions in the RD that affect cofactor
      responses. Using in vivo and in vitro transcription assays, we demonstrate that
      pssuE, a Cbl responsive promoter, is down-regulated not only by the cofactor,
      adenosine phosphosulphate (APS), but also by thiosulphate, and, that the same RD
      determinants are important for the response to both cofactors. We also
      demonstrate the effects of selected site-directed mutations on Cbl
      oligomerization and discuss these in the context of the structure. Based on the
      crystal structure and molecular modelling, we propose a model for the interaction
      of Cbl with adenosine phosphosulphate.

PMID- 17010380
TI  - Identification of Escherichia coli m2G methyltransferases: II. The ygjO gene
      encodes a methyltransferase specific for G1835 of the 23 S rRNA.
AB  - Escherichia coli ribosomal RNA contains five guanosine residues methylated at N2.
      The ygjO gene was previously predicted to methylate 16 S rRNA residue G966 due to
      its high sequence homology with the protein RsmC, responsible for G1207
      methylation. We have identified the target of YgjO as being m2G1835 of the 23 S
      rRNA and not m2G966 of the 16 S rRNA as expected. Knock-out of the ygjO gene
      leads to loss of modification at G1835, as revealed by reverse transcription.
      Moreover, the modification could be restored by in vivo complementation of the
      ygjO knock-out strain with a plasmid expressing ygjO. Recombinant YgjO protein is
      able to methylate in vitro protein-free 23 S rRNA, but not assembled 50 S
      subunits purified from the ygjO knock-out strain. The nucleotide m2G1835 is
      located in a functionally extremely important region of the ribosome, being
      located within intersubunit bridges of group B2. Growth competition assays reveal
      that the lack of the G1835 methylation causes growth retardation, especially at
      temperatures higher than optimal and in poor media. Based on these results we
      suggest that YgjO be renamed to RlmG in accordance with the accepted nomenclature
      for rRNA methyltransferases.

PMID- 17010381
TI  - Synergistic inhibition of HIV-1 envelope-mediated membrane fusion by inhibitors
      targeting the N and C-terminal heptad repeats of gp41.
AB  - The human immunodeficiency virus type-1 (HIV-1) envelope (Env) proteins that
      mediate membrane fusion represent a major target for the development of new AIDS
      therapies. Three classes of Env-mediated membrane fusion inhibitors have been
      described that specifically target the pre-hairpin intermediate conformation of
      gp41. Class 2 inhibitors bind to the C-terminal heptad repeat (C-HR) of gp41. The
      single example of a class 3 inhibitor targets the trimeric N-terminal heptad
      repeat (N-HR) of gp41 and has been postulated to sequestrate the N-HR of the pre
      hairpin intermediate through the formation of fusion incompetent heterotrimers.
      Here, we show that N(CCG)-gp41, a class 2 inhibitor, and N36(Mut(e,g)), a class 3
      inhibitor, synergistically inhibit Env-mediated membrane fusion for several
      representative HIV-1 strains (X4 and R5) in both a cell fusion assay (with
      membrane-bound CD4) and an Env-pseudo-typed virus neutralization assay. The
      mechanistic, as well as potential therapeutic, implications of these observations
      for HIV-Env-mediated membrane fusion are discussed.

PMID- 17010382
TI  - Familial Madras motor neuron disease (FMMND): study of 15 families from southern
      India.
AB  - Madras motor neuron disease (MMND) and Madras motor neuron disease variant
      (MMNDV) have an unique geographic distribution with concentration of majority of
      cases in the southern states of India. They have the characteristic features of
      onset in young, weakness and wasting of the limbs, multiple cranial nerve palsies
      particularly involving the 7th, 9th to 12th and sensorineural hearing impairment.
      In addition, all patients with MMNDV have bilateral optic atrophy. During the
      past 32 years, a total of 104 patients were diagnosed to have MMND and among
      these 25 patients with the familial form were further evaluated. In this report,
      we describe the clinical features of these 25 patients diagnosed to have familial
      Madras motor neuron disease (FMMND) or familial Madras motor neuron disease
      variant (FMMNDV), belonging to 15 families hailing from southern India. There
      were 10 patients diagnosed to have FMMND and 15 with FMMNDV. There were 14 males
      and 11 females with mean age at onset of 13.0+/-6.2 years and mean duration of
      illness of 73.6+/-74.0 months. Notably, the occurrence of MMNDV in the familial
      group (15 of 25 patients) was significantly more as compared to occurrence in the
      group with sporadic MMND (SMMND) [12 of 79 patients] (p=0.0002).

PMID- 17010383
TI  - Anti-Yo autoimmunity; dangerous for the brain but not the tumor?

PMID- 17010384
TI  - Boolean network analysis of a neurotransmitter signaling pathway.
AB  - BACKGROUND: A Boolean network is a simple computational model that may provide
      insight into the overall behavior of genetic networks and is represented by
      variables with two possible states (on/off), of the individual nodes/genes of the
      network. In this study, a Boolean network model has been used to simulate a
      molecular pathway between two neurotransmitter receptor, dopamine and glutamate
      receptor, systems in order to understand the consequence of using logic gate
      rules between nodes, which have two possible states (active and inactive).
      RESULTS: The dynamical properties of this Boolean network model of the
      biochemical pathway shows that, the pathway is stable and that, deletion/knockout
      of certain biologically important nodes cause significant perturbation to this
      network. The analysis clearly shows that in addition to the expected components
      dopamine and dopamine receptor 2 (DRD2), Ca(2+) ions play a critical role in
      maintaining stability of the pathway. CONCLUSION: So this method may be useful
      for the identification of potential genetic targets, whose loss of function in
      biochemical pathways may be responsible for disease onset. The molecular pathway
      considered in this study has been implicated with a complex disorder like
      schizophrenia, which has a complex multifactorial etiology.

PMID- 17010385
TI  - Harmful microalgae blooms (HAB); problematic and conditions that induce them.
AB  - HAB occurrence is becoming more frequent and problematic in marine recreational
      waters. However, the exploitation of the coastal area for recreational use is
      promoting the necessary conditions for the HAB increase. In terms of the harmful
      effects, we can consider two types of causative organism: the toxic producers and
      the high-biomass producers. Toxic events can be produced by a very low
      concentration of the causative organism. This characteristic implies a difficulty
      for the monitoring programs in relation to human health. It is important to point
      out in the context of human health and HAB events, that in some coastal regions
      (e.g. the Mediterranean basin) HABs are an emerging problem. In these regions,
      the local population and visitors may face a health risk that is difficult to
      measure. The monitoring of toxic species has mainly been associated -with
      shellfish farming. However, the risk of intoxication could become even greater in
      areas not subject to legislation of aquaculture activities.

PMID- 17010386
TI  - The impact of shrimp farming effluent on bacterial communities in mangrove
      waters, Ceara, Brazil.
AB  - The effects of shrimp farm effluents on bacterial communities in mangroves have
      been infrequently reported. Classic and molecular biology methods were used to
      survey bacterial communities from four mangroves systems. Water temperature,
      salinity, pH, total heterotrophic bacteria and maximum probable numbers of Vibrio
      spp. were investigated. Genetic profiles of bacterial communities were also
      characterized by polymerase chain reaction (PCR) amplification of eubacterial and
      Vibrio 16S rDNA using denaturing gradient gel electrophoresis (DGGE). Highest
      heterotrophic counts were registered in the mangrove not directly polluted by
      shrimp farming. The Enterobacteriaceae and Chryseomonas luteola dominated the
      heterotrophic isolates. Vibrio spp. pathogenic to humans and shrimps were
      identified. Eubacterial genetic profiles suggest a shared community structure
      independent of mangrove system. Vibrio genetic profiles were mangrove specific.
      Neither microbial counts nor genetic profiling revealed a significant decrease in
      species richness associated with shrimp farm effluent. The complex nature of
      mangrove ecosystems and their microbial communities is discussed.

PMID- 17010387
TI  - A model of the interaction between autoregulation and neural activation in the
      brain.
AB  - In this paper a model is proposed that predicts the response of the cerebral
      vasculature to changes in arterial blood pressure, arterial CO2 concentration and
      neural stimulation. Cerebral blood flow (CBF) is assumed to be controlled through
      changes in arterial compliance, and hence arterial resistance and volume, through
      three feedback mechanisms, which act in a linear additive manner, based on CBF,
      arterial CO2 and neural stimulus. Together with arterial, capillary and venous
      compartments, a tissue compartment is included, which contributes partly to the
      initial rise found in the deoxyhaemoglobin response to neural activation. Dynamic
      simulations of the model under different conditions show that there is
      significant interaction between the autoregulation and activation processes, and
      that the level of autoregulation has a strong influence on the CBF and
      deoxyhaemoglobin responses to neural activation. Overshoot in the
      deoxyhaemoglobin response is eliminated completely in the absence of this
      regulation. The feedback mechanism time constants significantly affect the CBF
      and deoxyhaemoglobin responses. Changes in arterial blood pressure (ABP) are
      found to have a strong influence on the neural activation response, with the
      amplitude of the response decreasing significantly at high baseline ABP. Dynamic
      changes in ABP also have a significant and potentially confounding impact on the
      measured deoxyhaemoglobin response to neural activation.

PMID- 17010388
TI  - A structured erythropoiesis model with nonlinear cell maturation velocity and
      hormone decay rate.
AB  - We develop a quasilinear structured model that describes the regulation of
      erythropoiesis, the process in which red blood cells are developed. In our model,
      the maturation velocity of precursor cells is assumed to be a function of the
      erythropoietin hormone, and the decay rate of this hormone is assumed to be a
      function of the number of precursor cells, unlike other models which assume these
      parameters to be constants. Existence-uniqueness results are established and
      convergence of a finite difference approximation to the unique solution of the
      model is obtained. The finite difference scheme is then used to investigate the
      effects of these nonlinear parameters on the model dynamics. Our results show
      that a velocity of precursor cells maturation rate which is an increasing
      function of the hormone level and a decay rate of the hormone which is an
      increasing function of the number of precursor cells have a stabilizing effect on
      the dynamics of the model. While assuming that one parameter is a function and
      letting the other be a constant stabilizes the oscillations in the mature cells
      level, the effect is more significant when both parameters are taken to be
      functions. A study of robustness with respect to the forms of these functions and
      parameter sensitivity is also carried out.

PMID- 17010389
TI  - DNA adduct formation and mutation induction by aristolochic acid in rat kidney
      and liver.
AB  - Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the
      causative factor for Chinese herb nephropathy. AA has been associated with the
      development of urothelial cancer in humans, and kidney and forestomach tumors in
      rodents. To investigate the molecular mechanisms responsible for the
      tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of
      AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats.
      Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body
      weight five times/week for 3 months. The rats were sacrificed 1 day after the
      final treatment, and the livers and kidneys were isolated. DNA adduct formation
      was analyzed by 32P-postlabeling and mutant frequency (MF) was determined using
      the lambda Select-cII Mutation Detection System. Three major adducts (7
      [deoxyadenosin-N6-yl]-aristolactam I, 7-[deoxyadenosin-N6-yl]-aristolactam II and
      7-[deoxyguanosin-N2-yl]-aristolactam I) were identified. There were strong linear
      dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to
      1967 adducts/10(8) nucleotides in liver and 95-4598 adducts/10(8) nucleotides in
      kidney. A similar trend of dose-responses for mutation induction also was found,
      the MFs ranging from 37 to 666 x 10(-6) in liver compared with the MFs of 78-1319
      x 10(-6) that we previously reported for the kidneys of AA-treated rats. Overall,
      kidneys had at least two-fold higher levels of DNA adducts and MF than livers.
      Sequence analysis of the cII mutants revealed that there was a statistically
      significant difference between the mutation spectra in both kidney and liver of
      AA-treated and control rats, but there was no significant difference between the
      mutation spectra in AA-treated livers and kidneys. A:T-->T:A transversion was the
      predominant mutation in AA-treated rats; whereas G:C-->A:T transition was the
      main type of mutation in control rats. These results indicate that the AA
      treatment that eventually results in kidney tumors in rats also results in
      significant increases in DNA adduct formation and cII MF in kidney. Although the
      same treatment does not produce tumors in rat liver, it does induce DNA adducts
      and mutations in this tissue, albeit at lower levels than in kidney.

PMID- 17010390
TI  - Four human FANCG polymorphic variants show normal biological function in hamster
      CHO cells.
AB  - Fanconi anemia (FA) is a rare cancer predisposition disease caused by mutations
      in at least 12 genes encoding proteins that cooperate to maintain genomic
      integrity. Variants of FA genes, including FANCG, have been identified in human
      population screening, but their potential reduction in protein function and role
      in cancer susceptibility is unclear. To test for possible dysfunction, we
      constructed plasmids containing four FANCG polymorphisms found in the human
      population and introduced them in the Fancg-deficient (fancg) KO40 line derived
      from AA8 hamster CHO cells. Expression of wild-type human FANCG provided fancg
      cells with complete phenotypic correction as assessed by resistance to the DNA
      crosslinking agent mitomycin C (MMC), thus providing a sensitive test for
      detecting the degree of complementation activity for the FANCG variants. We found
      that all four variants conferred levels of mitomycin C resistance as well as
      restoration of monoubiquitination of Fancd2, a key indicator of a functional FA
      protein pathway, similar to those observed in wild-type transfectants. Under the
      same conditions, the L71P amino acid substitution mutant, identified in an FA
      patient, gave no complementation. Using this novel system for determining FANCG
      functionality, we detect no decrement in function of the human FANCG polymorphic
      variants examined.

PMID- 17010392
TI  - The role of the right cerebral hemisphere in processing novel metaphoric
      expressions taken from poetry: a divided visual field study.
AB  - Previous research suggests that the right hemisphere (RH) may contribute uniquely
      to the processing of metaphoric language. However, most studies have focused on
      familiar metaphoric expressions. The present study used the divided visual field
      paradigm to examine the role of the right cerebral hemisphere in processing novel
      metaphoric expressions taken from poetry. In two experiments, participants were
      presented with four types of word pairs, literal, conventional metaphoric and
      novel metaphoric expressions and unrelated word pairs, and asked to perform a
      semantic judgment task. Two different SOAs: 400 and 1100 ms were used. The
      results of both experiments showed that responses to LVF/RH presented target
      words were more accurate and faster than responses to RVF/LH target words for
      novel metaphoric expressions, but not for other types of word pairs. These
      results support previous research indicating that during word recognition, the RH
      activates a broader range of related meanings than the LH, including novel,
      nonsalient meanings. The findings thus suggest that the RH may be critically
      involved in at least one important component of novel metaphor comprehension,
      i.e., the integration of the individual meanings of two seemingly unrelated
      concepts into a meaningful metaphoric expression.

PMID- 17010393
TI  - Visual search deficits in Williams-Beuren syndrome.
AB  - Williams-Beuren syndrome (WBS) is a rare genetic condition characterized by
      several physical and mental traits, such as a poor visuo-spatial processing and a
      relative strength in language. In this study we investigated how WBS subjects
      search and scan their visual environment. We presented 10 search displays on a
      computer screen to WBS subjects as well as control subjects, with the instruction
      to find a target out of several stimulus elements. We analyzed the eye movement
      patterns for fixation characteristics and systematicy of search. Fixations
      generally lasted longer in WBS subjects than in control subjects. WBS subjects
      made more fixations at a stimulus element they had already looked at and more
      fixations that were not aimed at a stimulus element at all, decreasing the
      efficiency of search. These outcomes lead to the conclusion that visual search of
      individuals with Williams-Beuren syndrome is less effective than in control
      subjects. This finding may be related to their motor deficits, an impaired
      processing of global visual information and/or deficits in working memory and
      could reflect impairments within the dorsal stream.

PMID- 17010394
TI  - Children with reading disorder show modality independent brain abnormalities
      during semantic tasks.
AB  - Neuroimaging studies have suggested that left inferior frontal gyrus, left
      inferior parietal lobule and left middle temporal gyrus are critical for semantic
      processing in normal children. The goal of the present functional magnetic
      resonance imaging (fMRI) study was to determine whether these regions are
      systematically related to semantic processing in children (9- to 15-year-old)
      diagnosed with reading disorders (RD). Semantic judgments required participants
      to indicate whether two words were related in meaning. The strength of semantic
      association varied continuously from higher association pairs (e.g., king-queen)
      to lower association pairs (e.g. net-ship). We found that the correlation between
      association strength and activation was significantly weaker for RD children
      compared to controls in left middle temporal gyrus and left inferior parietal
      lobule for both the auditory and the visual modalities and in left inferior
      frontal gyrus for the visual modality. These results suggest that the RD children
      have abnormalities in semantic search/retrieval in the inferior frontal gyrus,
      integration of semantic information in the inferior parietal lobule and semantic
      lexical representations in the middle temporal gyrus. These deficits appear to be
      general to the semantic system and independent of modality.

PMID- 17010395
TI  - A fine-grained analysis of facial expression processing in high-functioning
      adults with autism.
AB  - It is unclear whether individuals with autism are impaired at recognizing basic
      facial expressions, and whether, if any impairment exists, it applies to
      expression processing in general, or to certain expressions, in particular. To
      evaluate these alternatives, we adopted a fine-grained analysis of facial
      expression processing in autism. Specifically, we used the 'facial expression
      megamix' paradigm [Young, A. W., Rowland, D., Calder, A. J, Etcoff, N. L., Seth,
      A., & Perrett, D. I. (1997). Facial expression megamix: Tests of dimensional and
      category accounts of emotion recognition Cognition and Emotion, 14, 39-60] in
      which adults with autism and a typically developing comparison group performed a
      six alternative forced-choice response to morphs of all possible combinations of
      the six basic expressions identified by Ekman [Ekman, P. (1972). Universals and
      cultural differences in facial expressions of emotion. In J. K. Cole (Ed.),
      Nebraska symposium on motivation: vol. 1971, (pp. 207-283). Lincoln, Nebraska:
      University of Nebraska Press] (happiness, sadness, disgust, anger, fear and
      surprise). Clear differences were evident between the two groups, most obviously
      in the recognition of fear, but also in the recognition of disgust and happiness.
      A second experiment demonstrated that individuals with autism are able to
      discriminate between different emotional images and suggests that low-level
      perceptual difficulties do not underlie the difficulties with emotion
      recognition.

PMID- 17010396
TI  - Evaluation of the effectiveness and efficiency of the public health management of
      cases of infection due to Salmonella typhi/paratyphi in North East London.
AB  - OBJECTIVES: To evaluate the public health management of cases of Salmonella
      typhi/paratyphi in North East London in relation to national Public Health
      Laboratory Service (PHLS) guidelines and to determine the effectiveness and
      efficiency of current practice. STUDY DESIGN: A retrospective case-note review of
      laboratory-diagnosed cases of infection due to S. typhi/paratyphi in North East
      London in the 36 months from January 2002 to June 2004. RESULTS: Eighty-one cases
      were diagnosed with infection due to S. typhi/paratyphi during the study period.
      Sixty-seven cases (83%) were notified to the relevant local authority and 38 of
      these had at least the minimum number of follow-up samples recommended in
      national guidelines. A total of 251 contacts were screened with between one and
      six stool samples. One contact was identified who appeared to be a chronic
      carrier of S. typhi. The cost of identifying one person with a positive stool
      sample was estimated to be pounds sterling 3463 and the cost of detecting one
      probable chronic carrier was estimated at pounds sterling 17315. CONCLUSIONS: :
      There have been considerable difficulties in ensuring that case follow-up and
      contact screening is carried out according to national guidelines in North East
      London. Amongst those screened, the detection of excretors of pathogenic
      organisms was low. No chronic carriers were detected amongst the contacts of
      cases that acquired their infection abroad. Screening all such contacts is
      difficult to carry out and appears to be an inefficient use of resources.

PMID- 17010397
TI  - Specialist capacity in public health: are we hitting the target?
AB  - OBJECTIVES: The aim of this study was to audit specialist public health capacity
      in one strategic health authority (SHA), and to compare capacity with the targets
      suggested by the Faculty of Public Health (FPH). METHODS: A census of all public
      health specialists and specialists in training, working within the geographical
      boundary of one SHA, was performed in late 2004. The number of whole-time
      equivalent (WTE) public health specialists was quantified using a variety of
      methods, including the public health network database, informal networks,
      existing written reports, personal knowledge and telephone interviews. The number
      of specialists was compared with the targets suggested by the FPH and with other
      regions. RESULTS: There were 12 WTE public health specialists per million
      population in the SHA, and the FPH's target was 25 WTE per million population.
      There was a particular shortage of specialists in academic public health.
      CONCLUSIONS: There was a marked shortfall in specialist public health capacity in
      the SHA compared with the FPH's targets. Comparisons with the FPH's targets were
      difficult; the FPA used WTE as the metric, while the local public health network
      database provided information in terms of numbers of specialists and WTE data
      were time consuming to obtain. Comparisons with other regions were of limited use
      as the workforce data were not comparable. The FPH's targets were found to have
      little resonance outside the world of specialist public health, and so are
      unlikely to be helpful in securing local investment in specialist public health
      capacity. The service needs to be marketed, and new ways of inter-organizational
      and collaborative working and of expanding the wider public health workforce need
      to be examined in order to deliver effective public health.

PMID- 17010398
TI  - Influence of family history and lifestyle on blood pressure and heart rate in
      young adults in Jordan.
AB  - BACKGROUND: The most prevalent disease in Jordan is hypertension. Jordan is a
      small, middle-income developing country in the Middle East. It has a population
      of 5611202 people. Few studies have examined the associated cardiovascular risk
      factors in Jordan. DESIGN: The aim of this investigation was to explore specific
      lifestyles in Jordan, measuring blood pressure and heart rate through a
      randomized cross-sectional population study. METHODS: A total of 14310 adult
      males (7400) and females (6910) were selected in various regions of Jordan.
      Selected participants were interviewed by trained senior pharmacy students. They
      were asked whether they had hypertension or other cardiovascular disorders and if
      the answer was negative further questions were asked. This was followed by
      measurement of blood pressure and heart rate. Demographic data such as age, sex
      and nationality were also recorded, as was family history of hypertension. For
      each individual of the sample, systolic blood pressure (SBP), diastolic blood
      pressure (DBP) and heart rate were measured three times with 10-15min intervals
      in a sitting position and resting state. The Student's unpaired t-test was used
      for statistical analysis. Results were considered statistically significant when
      the P value was less than 0.05. RESULTS: A general trend in all the results
      tables was a lower blood pressure among those without a family history of
      cardiovascular disease and higher values among those with a family history of
      cardiovascular disease. CONCLUSION: This study demonstrates that SBP and DBP
      increase with all associated risk factors if a family history of hypertension is
      positive. This cross-sectional study revealed the presence of a consistent and
      strong relationship between certain lifestyle risk factors with an elevation in
      blood pressure concurrent with a positive family history of hypertension.

PMID- 17010391
TI  - Development of mussel mRNA profiling: Can gene expression trends reveal coastal
      water pollution?
AB  - Marine bivalves of the genus Mytilus are intertidal filter-feeders commonly used
      as biosensors of coastal pollution. Mussels adjust their functions to ordinary
      environmental changes, e.g. temperature fluctuations and emersion-related
      hypoxia, and react to various contaminants, accumulated from the surrounding
      water and defining a potential health risk for sea-food consumers. Despite the
      increasing use of mussels in environmental monitoring, their genome and gene
      functions are largely unexplored. Hence, we started the systematic identification
      of expressed sequence tags and prepared a cDNA microarray of Mytilus
      galloprovincialis including 1714 mussel probes (76% singletons, approximately 50%
      putatively identified transcripts) plus unrelated controls. To assess the
      potential use of the gene set represented in MytArray 1.0, we tested different
      tissues and groups of mussels. The resulting data highlighted the transcriptional
      specificity of the mussel tissues. Further testing of the most responsive
      digestive gland allowed correct classification of mussels treated with mixtures
      of heavy metals or organic contaminants (expression changes of specific genes
      discriminated the two pollutant cocktails). Similar analyses made a distinction
      possible between mussels living in the Venice lagoon (Italy) at the petrochemical
      district and mussels close to the open sea. The suggestive presence of gene
      markers tracing organic contaminants more than heavy metals in mussels from the
      industrial district is consistent with reported trends of chemical contamination.
      Further study is necessary in order to understand how much gene expression
      profiles can disclose the signatures of pollutants in mussel cells and tissues.
      Nevertheless, the gene expression patterns described in this paper support a
      wider characterization of the mussel transcriptome and point to the development
      of novel environmental metrics.

PMID- 17010399
TI  - Toxoplasma meningoencephalitis in HIV-seronegative patients: clinical patterns,
      imaging features and treatment outcome.
AB  - We evaluated the clinical and imaging features of cranial toxoplasmosis in
      patients without HIV infection. Between 1995 and 2005, 15 patients with
      serologically proven cranial toxoplasmosis were selected for clinical and imaging
      study from 233 patients with chronic meningitis and 364 patients with
      seizures/psychosis. All patients had poor immune status due to nutritional and
      metabolic causes. Neurological presentations included focal encephalitis,
      multifocal encephalitis and diffuse meningoencephalitis. The three groups had
      distinct symptoms and imaging features, with some overlap. Magnetic resonance
      imaging showed single or multiple nodular or ring-enhancing lesions often at the
      grey-white junction with subcortical white matter perifocal oedema. Within the
      large diffuse lesions there were discrete small haemorrhagic lesions and contrast
      medium administration showed fine-beaded parallel lines or small discrete nodules
      traversing the white matter suggesting perivenous spread. Complete clinical
      recovery was noted in 12 patients after several 6-week courses of pyrimethamine
      and sulfonamide/clindamycin. Five patients required two such courses, three
      patients required three courses, three patients required five courses and two
      patients required six courses for the final radiological healing, which was
      complete in nine patients. One patient was lost to follow-up and one patient died
      of cardiomyopathy. Knowledge of these three distinct initial presentations may
      help in the early diagnosis of cranial toxoplasmosis in HIV-seronegative
      patients. Prognosis in early cases is generally good but complete recovery may
      need several courses of treatment.

PMID- 17010400
TI  - Morbidity and mortality of wild animals in relation to outbreaks of Ebola
      haemorrhagic fever in Gabon, 1994-2003.
AB  - Antibody to Ebola virus was found in 14 (1.2%) of 1147 human sera collected in
      Gabon in 1981-1997. Six seropositive subjects were bled in the northeast in 1991,
      more than 3 years prior to recognition of the first known outbreak of Ebola
      haemorrhagic fever (EHF), whilst eight came from the southwest where the disease
      has not been recognised. It has been reported elsewhere that 98 carcasses of wild
      animals were found in systematic studies in northeastern Gabon and adjoining
      northwestern Republic of the Congo (RoC) during five EHF epidemics in August 2001
      to June 2003, with Ebola virus infection being confirmed in 14 carcasses. During
      the present opportunistic observations, reports were investigated of a further
      397 carcasses, mainly gorillas, chimpanzees, mandrills and bush pigs, found by
      rural residents in 35 incidents in Gabon and RoC during 1994-2003. Sixteen
      incidents had temporal and/or spatial coincidence with confirmed EHF outbreaks,
      and the remaining 19 appeared to represent extension of disease from such sites.
      There appeared to be sustained Ebola virus activity in the northeast in 1994
      1999, with sequential spread from 1996 onwards, first westwards, then southerly,
      and then northeastwards, reaching the Gabon-RoC border in 2001. This implies that
      there was transmission of infection between wild mammals, but the species
      involved are highly susceptible and unlikely to be natural hosts of the virus.

PMID- 17010401
TI  - Urinary free cortisol and cortisone excretion in healthy individuals: influence
      of water loading.
AB  - The influence of water loading on urinary excretion of free cortisol and
      cortisone was investigated in healthy men. The results were as follows: water
      loading tests (intake of 0.25-1.5 L) in a single individual showed that a water
      load of 1.5 L reliably increased the excretion of urine, free cortisol and
      cortisone (p < 0.01). Regression analyses gave significant correlations of urine
      volume with free cortisol and free cortisone, and of free cortisol and free
      cortisone. Corresponding results were obtained when water loading tests were
      performed in males who ingested 1.5 L of water (n = 8): the excretion of urine,
      free cortisol and free cortisone were significantly augmented; correlated was
      urine volume with free cortisol and free cortisone, and free cortisol with free
      cortisone. In a third set of tests, volunteers collected one 5 h urine (10:00
      15:00 h) after the intake of 3 x 0.1 or 0.5 L at 11:00, 12:00 and 14:00 h.
      Excretion of urine, free cortisol and free cortisone in males of the low water
      loading group (3 x 0.1 L) was 0.59 mL/min, and 8.2 or 15.0 microg/5 h;
      corresponding values in individuals ingesting 3 x 0.5 L of water were 1.5 mL/min
      (p < 0.01), 12.3 microg/5 h (p > 0.05) and 26.3 microg/5 h (p < 0.02). In
      summary, urinary free cortisol and cortisone excretion in healthy men depends on
      urine volume, especially during water diuresis. Thus, interpretation of free
      cortisol and especially of free cortisone excretion is only possible if subjects
      strictly control their fluid intake and if urine volume is considered an
      important pre-analytical parameter-otherwise, interpretation of urinary free
      cortisol results is difficult and of urinary free cortisone data remains tenuous
      at best.

PMID- 17010402
TI  - Structure and in vitro cytocompatibility of the gastropod shell of Helix pomatia.
AB  - Distinguishing features of biological constructions are high stability and
      adaptation to their environment. Beside biocompatibility, nontoxicity and
      degradability these characteristics are demanded for new biomaterials in the
      field of tissue engineering. This study investigated the chemical composition,
      the organization and the in vitro osteoconductive potential of the terrestrial
      gastropod shell (Helix pomatia) on CAL72 and human osteoblast-like cells.
      Chemical composition of the biomaterial was examined by X-ray diffraction (XRD)
      and scanning electron microscopy (SEM) was performed to analyze the architecture
      of the snail shell and the morphology of the seeded cells. A double staining
      procedure (FDA/PI) and a proliferation test (EZ4U) assessed the viability of the
      cells. Microscopical images showed the multilayered architecture of the aragonite
      shell with hexagonal crystals on the inner side. The cells spread well on the
      biomaterial and the highest proliferation rate could be measured with CAL72 cells
      on the inner shell surface. The osteoconductive effects of this natural
      biomaterial could encourage further experiments in the field of tissue
      engineering.

PMID- 17010403
TI  - Morphological changes of skeletal muscle, tendon and periosteum in the senescence
      accelerated mouse (SAMP6): a murine model for senile osteoporosis.
AB  - SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal
      model for senile osteoporosis. Previously we observed age-related changes of the
      bone in SAMP6. In the present study, we investigated the morphology of the
      skeletal muscle, tendon and periosteum in SAMP6 and age-matched normal mouse
      SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1
      and 2 months of age. As compared with SAMR1, the cross-sectional area of type I
      and type II muscle fibers of the soleus muscle were significantly low in SAMP6 at
      8 months of age. The projections in the interface of the muscle-tendon junctions
      were significantly decreased in SAMP6 at 8 months of age. The number of
      fibroblasts and the diameter of the tendon collagen fibers in Achilles fiber were
      significantly reduced in SAMP6 at 8 months of age. The diameter of Sharpey's
      fiber reduced in SAMP6 at 5 and 8 months of age. Some chondrocytes in the
      insertions of Achilles tendon and some osteogenic cells in the periosteum showed
      degenerative changes in SAMP6 at 5 and 8 months of age. The pronounced
      degenerative changes were detected in the skeletal muscle, muscle-tendon
      junction, tendon, tendon-bone interface and periosteum in SAMP6 with age. These
      findings indicated the atrophy of skeletal muscle, degeneration of tendon and
      periosteum in SAMP6, which may be involved in the bone loss for senile
      osteoporosis.

PMID- 17010404
TI  - Toxic effects of Microcystis cell extracts on the reproductive system of male
      mice.
AB  - In this paper, the reproductive toxicity of male mice treated with Microcystis
      aeruginosa cell extracts containing microcystins was examined. In contrast to the
      control group, male mice exposed intraperitoneally to 3.33 or 6.67 microg
      microcystins/kg body weight for 14 days had decreased mean body weight, and the
      mean absolute weight of the testes and epididymides was decreased. However, the
      mean relative weight of the testes increased compared to the controls. In
      addition, histological examination of microcystin-treated mice indicated that the
      testes were damaged and the space between the seminiferous tubules was more
      pronounced compared to control mice. The quality of mature sperm in the
      seminiferous tubules was also decreased in treated mice compared with the control
      group. Further studies showed that motility and viability of the sperm from
      microcystin-treated mice were reduced, but no significant difference was found in
      the concentration and abnormality of the sperm from treated mice compared to the
      control. This study indicated that microcystins had numerous toxic effects on the
      reproductive system of male mice.

PMID- 17010405
TI  - Neutralization of HPV16, 18, 31, and 58 pseudovirions with antisera induced by
      immunizing rabbits with synthetic peptides representing segments of the HPV16
      minor capsid protein L2 surface region.
AB  - Neutralizing antibody against human papillomavirus (HPV) minor capsid protein L2
      can cross-neutralize different HPV genotypes in vitro. To identify the segments
      containing the cross-neutralization epitopes of HPV16 L2, we characterized
      antisera obtained by immunizing two rabbits with each of the ten synthetic
      peptides of 14 to 20 amino acids (aa) long, which represents a part of the HPV16
      L2 sequence from aa 14 to 144. The antisera against the peptides within the
      region from aa 18 to 144 efficiently bound to HPV16 L1/L2-capsids and neutralized
      HPV16 pseudovirions, indicating that the region is displayed on the surface of
      the capsids and contains several neutralization epitopes. Antiserum against the
      peptide from aa 18 to 38 (anti-P18/38) cross-neutralized HPV18. Anti-P56/75 cross
      neutralized HPV18, 31, and 58. Anti-P61/75 and anti-P64/81 cross-neutralized
      HPV18 and 58. Anti-P96/115 and the antiserum induced by a mutant P96/115 (S and T
      at aa 101 and 112 were replaced with L and S, respectively) cross-neutralized
      HPV31 and 58. The mixture of equal volumes of three antisera, anti-P18/38, anti
      P56/75, and anti-mutant P96/115, neutralized HPV16, 18, 31, and 58 more
      efficiently than anti-P56/75 alone, suggesting that there is a synergistic effect
      of antibodies on the cross-neutralization. The cross-neutralization appears to be
      correlated with conserved aa sequences among HPV types. The data in this study
      provide a basis for designing vaccine antigens effective against a broader
      spectrum of the high-risk HPVs.

PMID- 17010406
TI  - Intracellular transport and stability of varicella-zoster virus glycoprotein K.
AB  - VZV gK, an essential glycoprotein that is conserved among the alphaherpesviruses,
      is believed to participate in membrane fusion and cytoplasmic virion
      morphogenesis based on analogy to its HSV-1 homolog. However, the production of
      VZV gK-specific antibodies has proven difficult presumably due to its highly
      hydrophobic nature and, therefore, VZV gK has received limited study. To overcome
      this obstacle, we inserted a FLAG epitope into gK near its amino terminus and
      produced VZV recombinants expressing epitope-tagged gK (VZV gK-F). These
      recombinants grew indistinguishably from native VZV, and FLAG-tagged gK could be
      readily detected in VZV gK-F-infected cells. FACS analysis established that gK is
      transported to the plasma membrane of infected cells, while indirect
      immunofluorescence demonstrated that gK accumulates predominately in the Golgi.
      Using VZV gK-F-infected cells we demonstrated that VZV gK, like several other
      herpesvirus glycoproteins, is efficiently endocytosed from the plasma membrane.
      However, pulse-labeling experiments revealed that the half-life of gK is
      considerably shorter than that of other VZV glycoproteins including gB, gE and
      gH. This finding suggests that gK may be required in lower abundance than other
      viral glycoproteins during virion morphogenesis or viral entry.

PMID- 17010407
TI  - Identification and functional characterization of AMVp33, a novel homolog of the
      baculovirus caspase inhibitor p35 found in Amsacta moorei entomopoxvirus.
AB  - Members of the baculovirus p35 gene family encode proteins that specifically
      inhibit caspases, cysteine proteases that are involved in apoptosis. To date, p35
      homologs have only been found in baculoviruses. We have identified AMVp33, a gene
      from Amsacta moorei entomopoxvirus with low but significant homology to
      baculovirus p35 genes. Expression of AMVp33 blocked apoptosis in several
      different insect and human cell lines. Purified recombinant P33 protein was an
      efficient inhibitor of insect and human effector caspases, but not initiator
      caspases. P33 was cleaved by effector caspases, and the resulting cleavage
      fragments stably associated with the caspases. Mutation of the predicted caspase
      cleavage site in P33 eliminated cleavage, caspase inhibition and anti-apoptotic
      function. Thus, AMVp33 encodes a caspase inhibitor similar to baculovirus P35
      with a preference for effector caspases. This is the first report of a p35
      homolog from any viral or cellular genome outside of the baculovirus family.

PMID- 17010408
TI  - A role for rhodopsin in a signal transduction cascade that regulates membrane
      trafficking and photoreceptor polarity.
AB  - This review summarizes the most recent progress in the understanding of the role
      of rhodopsin C-terminal domain in the regulation of intracellular trafficking and
      photoreceptor morphogenesis. A proposed cascade of molecular interactions,
      initiated by the rhodopsin C-terminal sequence VXPX-COOH during trafficking from
      the Golgi/TGN in retinal photoreceptors, is relayed by the small GTPase ARF4 to
      the downstream effectors. One of the candidates for an ARF4 effector is the ARF
      GAP ASAP1, which may function as a subunit of, or form a novel protein coat
      involved in trafficking from the TGN and in cytoskeletal remodeling, whose
      assembly is regulated by the binding of ARF4 to rhodopsin, and whose function is
      essential for the polarized trafficking toward the ROS.

PMID- 17010409
TI  - Evaluation of inner retinal function in myopia using oscillatory potentials of
      the multifocal electroretinogram.
AB  - PURPOSE: Oscillatory potentials have been suggested to arise from the inner
      retina at the level of amacrine cells and inner plexiform layer and they are
      thought to provide a non-invasive assessment of inner retinal function. We sought
      to investigate the response dynamics of the inner retina of adult emmetropes and
      myopes by analysing the oscillatory potentials of the multifocal
      electroretinogram (mfERG) in these groups. METHODS: Eleven emmetropes and 18
      myopes underwent mfERG testing using VERIS 5.1.5X. Myopes were further separated
      based on whether their myopia was stable (n=9) or progressing (n=9). Oscillatory
      potentials were recorded using a modified mfERG stimulation technique, the slow
      flash paradigm, and they were extracted using band-pass filtering from 100 to 300
      Hz. The slow flash mfERG stimulus array consisted of 103-scaled hexagons and
      flickered according to a pseudorandom binary m-sequence (2(13)-1). Amplitudes and
      implicit times of the first-order oscillatory potentials were analysed. RESULTS:
      There were significant differences in the implicit time of the oscillatory
      potentials of the emmetropes, stable myopes and progressing myopes
      (F(2,25)=3.663, p=0.043). Progressing myopes had significantly shorter implicit
      times compared to emmetropes (p=0.026 by 1.0-4.7 ms) and stable myopes (p=0.043
      by 0.8-1.3 ms), whereas implicit times of stable myopes and emmetropes were
      similar. There were no statistically significant differences in amplitude of the
      oscillatory potentials between the groups (F(2,25)=0.890, p=0.426). CONCLUSIONS:
      Significant differences in multifocal oscillatory potentials between stable and
      progressing myopes were found. This finding is further evidence of an inner
      retinal involvement in human myopia progression and may suggest an underlying
      alteration to dopaminergic or GABAergic retinal systems.

PMID- 17010410
TI  - Expression of semaphorins, vascular endothelial growth factor, and their common
      receptor neuropilins and alleic loss of semaphorin locus in epithelial ovarian
      neoplasms: increased ratio of vascular endothelial growth factor to semaphorin is
      a poor prognostic factor in ovarian carcinomas.
AB  - Semaphorins (SEMAs) compete with vascular endothelial growth factor (VEGF) for
      receptor neuropilin 1 (NP1) and 2 (NP2) and suppress angiogenesis. To clarify the
      involvement of SEMA and VEGF in the development and progression of ovarian
      carcinoma, we analyzed the immunohistochemical expression of SEMA, VEGF, NP1, and
      NP2 in 105 epithelial ovarian tumors. In addition, loss of heterozygosity at SEMA
      gene loci was examined. Strong expression of SEMA was found in 48% of benign, 33%
      of borderline tumors, and 13% of carcinomas (P < .05). Positivity for SEMA was
      significantly decreased in stage IV carcinomas and the expression of SEMA was
      significantly lower in peritoneal metastases than in primary lesions. Expression
      of SEMA showed a weak inverse correlation with microvessel density, but the
      correlation was not statistically significant. Loss of heterozygosity at SEMA3B
      or SEMA3F was demonstrated in none of the benign tumors, 8% of borderline tumors,
      and 29% of carcinomas. Expression of NP1 and NP2 was significantly higher in
      carcinomas than in benign tumors (P < .0001 and .0002, respectively). Patients
      with ovarian carcinoma with a high VEGF/SEMA ratio showed poorer survival than
      those with a low VEGF/SEMA ratio (P = .005). Decreased expression of SEMA and
      increased expression of NP1 and NP2 are characteristics of ovarian carcinomas,
      and loss of SEMA expression may play an important role in ovarian carcinoma
      progression. A high VEGF/SEMA ratio has adverse prognostic significance in
      patients with ovarian carcinoma.

PMID- 17010411
TI  - Aspirin resistance: what, why and when?

PMID- 17010412
TI  - Surface-dependent expression in the platelet GPIb binding domain within human von
      Willebrand factor studied by atomic force microscopy.
AB  - Adsorption of plasma proteins such as von Willebrand factor (vWF) on thrombogenic
      surfaces can induce conformational changes in tertiary structure so that the
      prothrombotic functional epitopes are exposed for interactions with platelets,
      resulting in platelet adhesion and thrombus formation. Thus, understanding
      platelet binding following changes in the structure of vWF is critical in
      understanding the mechanisms of thrombogenesis. The present study examined the
      accessibility of platelet binding epitopes within vWF adsorbed on two different
      thrombogenic surfaces, a hydrophobic synthetic surface and collagen VI coated
      substrates, under physiological buffer conditions using atomic force microscopy
      (AFM) in combination with immunogold labeling. Our results demonstrated that the
      glycoprotein Ib (GPIb) binding domain in vWF undergoes changes when adsorbed on
      collagen VI compared to vWF on a hydrophobic synthetic surface. This study
      provides a basis for a novel approach to understand the molecular mechanisms of
      surface-induced thrombosis by directly examining the structure-function
      relationships of plasma proteins involved in the thrombus formation.

PMID- 17010413
TI  - Contributions of Ernst L. Wynder to chronic disease control worldwide and to
      preventive medicine.
AB  - Ernst L. Wynder is internationally known for his important discoveries in the
      field of human chronic disease causation, that is the underlying mechanisms,
      studied in various animal models, as a foundation for recommendations on the
      prevention of these diseases. These include coronary heart disease, and the main
      human cancers including cancer of the lung, caused by traditional smoking habits,
      and the nutritionally linked cancers, namely cancer of the breast, prostate,
      colon, pancreas, and urinary bladder. Much of this research was performed in a
      chronic disease prevention institution--created by Dr. Wynder--the American
      Health Foundation. There were outreach programs to educate people about proper
      lifestyles to secure disease prevention, including beginning health education in
      children.

PMID- 17010414
TI  - Developmental programming in sheep: administration of testosterone during 60-90
      days of pregnancy reduces breeding success and pregnancy outcome.
AB  - Evidence suggests that exposure to excess steroids during critical periods of
      fetal development leads to reproductive disorders. Exposure of female lambs to
      excess testosterone (T) from Days 60 to 90 of gestation (T60-90; term, 147 days)
      delayed onset of the LH surge and resulted in to male-typical reproductive
      behavior. The objectives of this study were to test the ability of T60-90 ewes to
      mate, conceive and lamb during the first three breeding seasons (Years 1, 2 and
      3). Pregnant Suffolk ewes were injected with T propionate in cottonseed oil
      (100mg, im twice weekly) or vehicle (control; C) from Days 60 to 90 of gestation.
      In Year 1, ewes (C=12, T60-90=12) were kept with a vasectomized ram for 3 months
      and markings/visual observation of copulations were recorded. Rams had paint
      applied to their chest to facilitate detection of estrus and mating. All C but
      only three T60-90 ewes were marked (P<0.001). All ewes were then estrus
      synchronized with two injections of prostaglandin F2alpha (20mg, im) given 11
      days apart and allowed to mate with a painted, fertile ram. Nine of 12 C and 4 of
      12 T60-90 ewes (P=0.1) were mated. Based on estrus and long-term monitoring of
      progesterone, more C than T60-90 became pregnant (82 and 18%, respectively;
      P<0.01). In Year 2, to maximize ram exposure, two C and two T60-90 estrus
      synchronized ewes were placed with a painted, fertile ram at a time and mated
      ewes were removed to a nearby pen to force mating with others. Twenty-four hour
      video monitoring revealed the rams mated more C than T60-90 ewes (83 and 25%,
      respectively; P=0.01). In both Years 1 and 2, the rams preferred C over T60-90
      ewes; therefore in Year 3 rams were given access only to T60-90 ewes. Only four
      T60-90 estrus-synchronized ewes were placed with a painted ram at a time. Not
      given an option, 91% of the T60-90 ewes were marked resulting in 4 of 11 (36%;
      first-service pregnancy rate in the breeding herd was 91%) ewes becoming pregnant
      to the synchronized estrus. Collectively these studies showed that fertility in
      T60-90 females was severely compromised, even after overcoming ram preference for
      controls.

PMID- 17010415
TI  - Plasma pregnancy-associated glycoprotein-1 (PAG-1) concentrations during
      gestation in Neospora-infected dairy cows.
AB  - The aim of this study was to determine whether plasma pregnancy-associated
      glycoprotein-1 (PAG-1) concentrations in pregnancy are affected by persistent
      Neospora caninum infection in dairy cows. The data analyzed were derived from 22
      multiparous cows: 16 N. caninum-seropositive and 6 N. caninum-seronegative
      animals (used as controls). Three of the 16 seropositive cows aborted during the
      study period and the corresponding data were analyzed separately. Pregnancy
      diagnoses were performed on day 40 post-insemination by transrectal ultrasound,
      and by palpation per rectum on days 90, 120, 150, 180 and 210. Blood samples were
      collected from each animal immediately before each pregnancy diagnosis, and then
      at parturition or at the time of abortion detection. Plasma was tested for
      antibodies against N. caninum and PAG-1 concentrations were determined by
      radioimmunoassay. In non-aborting animals, the effects of neosporosis
      (seropositive versus seronegative), N. caninum antibody levels, semen providing
      bull, sex of the newborn, and day of gestation on PAG-1 concentrations were
      evaluated by GLM repeated measures analysis of variance. The effect of the
      gestation period (first half versus second half) on the N. caninum antibody titer
      was established by the Student's t-test in seropositive cows. A significant
      positive effect of gestation day on PAG-1 concentrations was observed (d.f.=6;
      F=12.6; P<0.0001). For all cows, PAG-1 concentrations increased steadily during
      the course of gestation, with peak concentrations recorded at parturition.
      Neosporosis (P=0.493), N. caninum antibody levels (P=0.921), sex of the newborn
      (P=0.856) and semen providing bull (P=0.087) had no effect on plasma PAG-1
      concentration. There was a significant 52% increase (P<0.0001) in N. caninum
      antibody titers during the second half of gestation compared to the first half.
      The fates of the three aborting cows were abortion on gestation day 215 in one,
      and fetus mummification diagnosed on gestation days 180 and 210, respectively, in
      the remaining two cows. A luteolytic dose of prostaglandin was applied 30 days
      after mummification diagnosis in these last two cows, and fetus expulsion was
      detected on days 215 and 250, respectively. Two of the aborted fetuses were
      submitted to laboratory analysis and the presence of N. caninum was confirmed by
      specific PCR. In the cows with a mummified fetus, PAG-1 concentrations were low
      or undetectable when the diagnosis was made. These findings suggest that N.
      caninum infection has no effect on placental function in chronically infected,
      cows not suffering abortion, while PAG-1 measurements in aborting animals provide
      a useful indication of feto-placental status.

PMID- 17010416
TI  - Effect of post-thaw dilution with autologous prostatic fluid on dog semen
      motility and sperm acrosome status.
AB  - The aim of this study was to evaluate the effect of post-thaw dilution with
      autologous prostatic fluid on motility parameters, longevity and acrosome status
      of frozen-thawed dog spermatozoa. After semen collection, seminal plasma was
      separated by centrifugation and stored frozen until use. Sperm pellets were
      diluted in two steps with an egg yolk-Tris extender to a final concentration of
      5% glycerol and 0.5% Equex STM Paste. After thawing, semen was diluted 1:2 either
      with Tris buffer or with the autologous prostatic fluid. Motility was evaluated
      using a phase contrast microscope and a computer-assisted motility analyser
      system immediately after thawing and at hourly intervals up for 4h at 38 degrees
      C. The status of acrosomes was assessed with Spermac stain at thawing and after 2
      h of incubation. Motility and straight line velocity were initially higher in
      prostatic fluid-diluted samples (0 h and 0 and 1h, respectively), but decreased
      to values similar to those of Tris-diluted samples in a time-dependent manner. In
      contrast, both the curvilinear velocity and amplitude of lateral head
      displacement were lower in prostatic fluid-diluted samples (1 and 3 h and 0, 1
      and 3 h, respectively). The dilution did not have any significant effect on the
      percentage of acrosome-intact spermatozoa at either thawing or after 2 h. The
      pattern of motility of prostatic fluid-diluted samples suggests a reduction in
      hyperactivated motility with time, even though prostatic fluid neither prolonged
      spermatozoa longevity nor had any effect on the status of spermatozoa acrosomes.

PMID- 17010417
TI  - Low concentrations of MEM vitamins during in vitro maturation of porcine oocytes
      improves subsequent parthenogenetic development.
AB  - To investigate the effects of water-soluble vitamin supplementation for IVM/IVC
      of porcine oocytes and evaluate maturation and developmental capacity in vitro,
      porcine cumulus oocyte complexes (COCs) was matured in NCSU-23-based medium with
      water-soluble vitamins for 44 h and then cultured in PZM-3 for 7 days following
      activation. The COCs were allocated into five treatment groups and matured in
      various concentrations of MEM vitamins (control, 0.05, 0.1, 0.2, 0.4, and 1x).
      Metaphase II plates of the cumulus-free oocytes were observed following Hoechest
      33258 staining. The COCs were allocated into four treatment groups, matured in
      various concentrations of MEM vitamins (control, 0.05, 0.1, 0.2, and 0.4x) and
      cultured in PZM-3 following activation. Also, COCS were matured without MEM
      vitamins and cultured in PZM-3 with various concentrations (control, 0.1, 0.4,
      1.0, and 2.0 x) of MEM vitamins. Furthermore, 2 x 2 factorial (IVM/IVC)
      experiments were performed in IVM medium with or without 0.05 x MEM vitamins and
      IVC medium with or without 0.4x MEM vitamins to examine the in vitro development
      of parthenogenetic embryos. Maturation rates of COCs treated with MEM vitamins
      did not differ significantly among groups. However, compared to the control
      group, oocytes matured with the addition of 0.05 x MEM vitamins developed to
      blastocysts at a higher percentage (P<0.05) following activation and culture in
      PZM-3 without MEM vitamins. Total cell number of blastocysts was significantly
      higher in the 0.05 x group. Addition of 0.4x MEM vitamins decreased (P<0.05)
      cleavage and blastocyst developmental rates compared with 0.05 x MEM vitamins
      treated group. In contrast, addition of vitamins to PZM-3 medium for in vitro
      culture of activated porcine oocytes did not affect development. In conclusion,
      addition of a low concentration of MEM vitamins to IVM medium for porcine oocytes
      enhanced subsequent development and improved embryo quality.

PMID- 17010418
TI  - Luteinizing hormone and follicle-stimulating hormone receptors and their
      transcribed genes (mRNA) are present in the lower urinary tract of intact male
      and female dogs.
AB  - In dogs, one of the side effects of neutering is the development of urinary
      incontinence. The relationship between neutering and urinary incontinence caused
      by acquired urethral sphincter mechanism incompetence (USMI) has been reported.
      Recently, GnRH analogue treatment that suppresses elevated plasma gonadotrophin
      concentrations post-spaying has been successfully used in incontinent bitches.
      These data and the fact that non-gonadal tissues may contain receptors for LH
      (LHR) and FSH (FSHR) suggest that there might be a functional relationship
      between gonadotrophins and the lower urinary tract in dogs. This study aimed to
      investigate the presence of LHR and FSHR in the lower urinary tract of intact
      male and female dogs. Four regions of the lower urinary tract, i.e. (i) body of
      the bladder, (ii) neck of the bladder, (iii) proximal urethra and (iv) distal
      urethra were collected from 10 healthy dogs (5 males and 5 anoestrous females).
      In situ hybridization and immunohistochemistry were performed to characterise the
      presence of receptor mRNA and receptor protein. Staining was rated semi
      quantitatively, incorporating both the distribution and intensity of specific
      staining. The distribution of receptor expression in different tissue layers
      (epithelium, subepithelial stroma and muscle) in each region was statistically
      analyzed. Luteinizing hormone receptor and FSHR mRNA and protein were present in
      all four regions and in three tissue layers of males and females. Irrespective of
      region and layer, female dogs expressed significantly higher expression for LHR
      mRNA (P<0.001), LHR protein (P<0.05) and FSHR protein (P<0.001). The expression
      of LHR and FSHR mRNA and protein was not uniform and depended on region, tissue
      layer and gender. The expression of LHR mRNA was higher in the bladder, compared
      to the urethra (P<0.05). The FSHR mRNA significantly increased from the bladder
      to the urethra. Protein expression for LHR and FSHR was highest in the proximal
      urethra (P<0.05). The overall expression for LHR and FSHR at both mRNA and
      protein levels was highest in the epithelium, intermediate to low in the
      subepithelial stroma and muscle. A significant interaction between region and
      tissue layer showed that mRNA and protein expression for LHR and FSHR decreased
      from the bladder to the urethra in the epithelium and subepithelial stroma. In
      contrast, it gradually increased from the bladder to the urethra in the muscle.
      In conclusion, the present study showed that both mRNA and protein for LHR and
      FSHR were expressed in the canine lower urinary tract, and the expression levels
      varied between genders and among regions and tissue layers. The presence of these
      receptors suggests that gonadotrophins have a role in the physiology and/or
      pathology of the lower urinary tract function in the dog.

PMID- 17010419
TI  - One year old fillies can be successfully used as embryo donors.
AB  - One year old fillies are able to conceive but, usually, not to give birth to a
      living foal. Although embryo transfer allows the production of foals from mature
      mares with repeated pregnancy losses, no reports are available on the use of one
      year old fillies as embryo donors. To evaluate this possibility, eleven 12-16
      months old Haflinger mares were inseminated with fresh semen and subjected to
      embryo recovery. Some of the recovered embryos were non-surgically transferred
      into synchronized mature recipients. Pregnancies were terminated using PGF2alpha
      at day 25. Fillies' embryo recovery rate and their recipients' pregnancy rate at
      day 25 were compared with those achieved in two years old and mature mares of the
      same breed, subjected to the same management. Embryo recovery rate was 21/44
      (47.7%), 12/16 (75%) and 22/26 (84.6%) (P>0.01) for one year old, two years old
      and mature mares, respectively. Five/7 (71.4%) one year old donors' embryos
      resulted in a pregnancy after transfer and 4/7 (57.1%) developed until day 25.
      Significant differences in pregnancy rates after transfer between donors' age
      groups were not observed; no short term side effects resulted from the use of
      fillies as embryo donors. This study showed that one year old mares employed as
      embryo donors produce embryos both morphologically normal and able to develop in
      recipient mares at least up to day 25 of pregnancy.

PMID- 17010420
TI  - Decreased white-matter density in a left-sided fronto-temporal network in
      children with developmental language disorder: evidence for anatomical anomalies
      in a motor-language network.
AB  - The neurophysiological and neuroanatomical foundations of developmental language
      disorder (DLD) are still a matter of dispute. A main argument is that children
      with DLD show atypical anatomical asymmetries of speech-relevant brain areas,
      which possibly affect efficient language processing. In contrast to previous
      anatomical studies in DLD children, this study employed voxel based morphometry
      (VBM) in order to search for brain anomalies outside the classical language
      areas. Children with DLD (n=21) and healthy children (n=21) matched for age, sex,
      hand preference, and education were studied using high-resolution MRI scans.
      Using a new variant of the voxel-based morphometry technique (augmented VBM), the
      brains of children with DLD and control children were compared with respect to
      white matter (WM) and grey matter (GM) differences. In addition, simple hand
      motor tests were used to uncover possible motor impairments in DLD children. We
      found decreased WM volumes in a left-hemispheric network comprising the motor
      cortex, the dorsal premotor cortex, the ventral premotor cortex, and the planum
      polare on the superior temporal gyrus. In addition, DLD children exhibited motor
      impairments in most of the applied motor tests. These results provide strong
      evidence that children with DLD have anomalous anatomy in a left-sided network
      comprising motor and language areas. Thus, this study supports the suggestion
      that motor and language functions are equally impaired because the underlying
      anatomical underpinnings are regionally identical.

PMID- 17010421
TI  - The role of neuronal signaling in controlling cerebral blood flow.
AB  - Well-regulated blood flow within the brain is vital to normal function. The
      brain's requirement for sufficient blood flow is ensured by a tight link between
      neural activity and blood flow. The link between regional synaptic activity and
      regional cerebral blood flow, termed functional hyperemia, is the basis for
      several modern imaging techniques that have revolutionized the study of human
      brain activity. Here, we review the mechanisms of functional hyperemia and their
      implications for interpreting the blood oxygen level-dependent (BOLD) contrast
      signal used in functional magnetic resonance imaging (fMRI).

PMID- 17010423
TI  - Exhaustive crystal structure search and crystal modeling of beta-chitin.
AB  - An exhaustive search of the crystal structure of beta-chitin was carried out by
      simultaneously optimizing all the structural parameters based on published X-ray
      diffraction data and stereochemical criteria. The most probable structure was
      characterized by a parallel-up chain polarity, a gg orientation of hydroxymethyl
      groups and an intermolecular hydrogen bond along the a-axis, which essentially
      reproduced the original structure proposed by Gardner and Blackwell. The proposed
      crystal structure was subsequently subjected to crystal modeling using the AMBER
      force field. The probable orientation of hydroxyl groups and their motional
      behaviors is proposed based on calculations for the crystal models identified.
      Solvated crystal models exhibited a slightly deformed structure with the
      formation of appreciable numbers of hydrogen bonds along the b-axis.

PMID- 17010422
TI  - Effects of perceptual and conceptual similarity in lexical priming of young
      children who stutter: preliminary findings.
AB  - The purpose of this study was to investigate the influence of conceptual and
      perceptual properties of words on the speed and accuracy of lexical retrieval of
      children who do (CWS) and do not stutter (CWNS) during a picture-naming task.
      Participants consisted of 13 3-5-year-old CWS and the same number of CWNS. All
      participants had speech, language, and hearing development within normal limits,
      with the exception of stuttering for CWS. Both talker groups participated in a
      picture-naming task where they named, one at a time, computer-presented, black-on
      white drawings of common age-appropriate objects. These pictures were named
      during four auditory priming conditions: (a) a neutral prime consisting of a
      tone, (b) a word prime physically related to the target word, (c) a word prime
      functionally related to the target word, and (d) a word prime categorically
      related to the target word. Speech reaction time (SRT) was measured from the
      offset of presentation of the picture target to the onset of participant's verbal
      speech response. Results indicated that CWS were slower than CWNS across priming
      conditions (i.e., neutral, physical, function, category) and that the speed of
      lexical retrieval of CWS was more influenced by functional than perceptual
      aspects of target pictures named. Findings were taken to suggest that CWS tend to
      organize lexical information functionally more so than physically and that this
      tendency may relate to difficulties establishing normally fluent speech and
      language. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to (1)
      communicate the relevance of examining lexical retrieval in relation to childhood
      stuttering and (2) describe the method of measuring speech reaction times of
      accurate and fluent responses during a picture-naming task as a means of
      assessing lexical retrieval skills.

PMID- 17010424
TI  - Involvement of toll-like receptor 4 in the inflammatory reaction induced by
      hydroxyapatite particles.
AB  - Hydroxyapatite (HA) is widely used to coat metal parts in order to improve their
      biocompatibility. Analysis of retrieved tissues associated with failed implants,
      suggest that phagocytosis of HA wear debris by monocytes/macrophages might
      provide a potent stimulus for the release of a variety of cytokines. Phagocytosis
      involved a large variety of cellular receptors like toll-like receptors that
      results in activation of the transcriptional nuclear factor-kappaB (NF-kappaB)
      via a cell-signalling pathway. In the present paper, we aimed to evaluate the
      role of the toll-like receptor 4 (TLR4) in the production of inflammatory
      cytokines induced by HA particles using TLR4(+) and TLR4(-) peritoneal
      macrophages. We investigated the production of TNF-alpha and the activation of
      the nuclear transcription factor NF-kappaB. Our data clearly show for the first
      time that the production of TNF-alpha by macrophages exposed to HA particles was
      TLR4 dependent but not the activation of NF-kappaB. All these results open future
      therapies to reduce the inflammatory response induced by HA biomaterials.

PMID- 17010426
TI  - The expression of the neonatal sarcoplasmic reticulum Ca2+ pump (SERCA1b) hints
      to a role in muscle growth and development.
AB  - The neonatal isoform of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 1
      (SERCA1b) is a Ca2+ pump with a well-known developmentally regulated transcript
      level but an undefined protein expression and function. Specific antibodies were
      generated to show that SERCA1b is exclusively expressed in myoblasts and myotubes
      of cultured and regenerating muscle. However, the SERCA1b protein was not
      detectable in normal adult fast and slow muscles. Studies of the in vitro
      differentiating myogenic cell lines C2C12 and sol8 showed that SERCA1b is the
      main SERCA1 protein isoform induced during differentiation and that it is found
      in the myotubes. Remarkably in BC3H1 cells, which show incomplete differentiation
      and are reluctant to form myotubes, express the SERCA1b mRNA but not the
      corresponding protein. SERCA1b protein was also absent from stretched or
      denervated adult soleus, in spite of the fact that its mRNA level was
      upregulated. SERCA1b accounts for nearly the total of SERCA1 expression in the
      diaphragm of newborn mice, which suggests that the insufficient function and
      development of the diaphragm in the SERCA1 null mutant mice may be due to the
      lack of SERCA1b. Our studies point to an important regulation of SERCA1b
      expression at the protein level and hints to a role in the growth of the
      developing muscle.

PMID- 17010427
TI  - Postnatal developmental changes in Ca2+ homeostasis in supraoptic magnocellular
      neurons.
AB  - Supraoptic magnocellular neurons (SMNs) undergo dramatic changes in morphological
      and electrical properties during postnatal development. We investigated the
      developmental change in Ca2+ homeostasis in SMNs. The decay rate of Ca2+
      transients markedly increased during the third postnatal week (PW3) to an adult
      level. This increase in the Ca2+ decay rate was paralleled by hypertrophy of the
      SMN somata. Activity of Na+/Ca2+ exchanger (Na/CaX) and sarcoendoplasmic
      reticulum Ca2+-ATPase (SERCA) was quantified as a decrement in the Ca2+ decay
      rate caused by extracellular [Na+] reduction and that by thapsigargin,
      respectively. SERCA activity was negligible during PW2, and markedly increased
      during PW3. SERCA activity and soma size remained stable thereafter. Na/CaX
      activity was a major Ca2+-clearance mechanism (CCM) during PW2, increased further
      during PW3, but was negligible in mature SMNs (PW10). In parallel with the
      decrease in Na/CaX activity, endogenous Ca2+ buffering capacity declined,
      resulting that the apparent Ca2+ decay rate remained relatively constant between
      PW4 and PW10. Replacement of intracellular K+ with Li+ had no effect on Na/CaX
      activity, suggesting that NCX rather than NCKX comprises Na/CaX. These findings
      indicate a developmental shift in the balance of CCMs from Ca2+ extrusion via NCX
      toward Ca2+ sequestration into endoplasmic reticulum via SERCA.

PMID- 17010425
TI  - Continuing differentiation of human mesenchymal stem cells and induced
      chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold.
AB  - Nanofibers have recently gained substantial interest for potential applications
      in tissue engineering. The objective of this study was to determine whether
      electrospun nanofibers accommodate the viability, growth, and differentiation of
      human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and
      chondrogenic (hMSC-Ch) derivatives. Poly(d,l-lactide-co-glycolide) (PLGA) beads
      with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an
      average diameter of 760+/-210 nm. The average Young's modulus of electrospun PLGA
      nanofibers was 42+/-26 kPa, per nanoindentation with atomic force microscopy
      (AFM). Human MSCs were seeded 1-4 weeks at a density of 2 x 10(6)cells/mL in PLGA
      nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained
      as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days
      after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached
      to PLGA nanofibers. The overwhelming majority of hMSCs was viable and
      proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed
      live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in
      PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic
      cells. Histological assays revealed that hMSCs continuously differentiated into
      chondrogenic cells and osteogenic cells after 2 week incubation in PLGA
      nanofibers. Taken together, these data represent an original investigation of
      continuous differentiation of hMSCs into chondrogenic and osteogenic cells in
      PLGA nanofiber scaffold. Consistent with previous work, these findings also
      suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but
      also as a 3D carrier vehicle for lineage specific cells.

PMID- 17010428
TI  - Quetiapine lowers sympathetic and hyperthermic reactions due to cerebral
      injection of orexin A.
AB  - Since no experiment regarding a possible relation between quetiapine and orexin A
      has been reported in international literature, this experiment tested the effect
      of quetiapine on the sympathetic and thermogenic effects induced by orexin A. The
      firing rates of the sympathetic nerves to interscapular brown adipose tissue
      (IBAT), along with IBAT, colonic temperatures and heart rate were monitored in
      urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A
      (1.5 nmol) into the lateral cerebral ventricle and over a period of 150 min after
      the injection. The same variables were monitored in rats with an intraperitoneal
      administration of quetiapine (5 or 10 mg/kg bw), injected 30 min before the
      orexin administration. The results show that orexin A increases the sympathetic
      firing rate, IBAT, colonic temperatures and heart rate. This increase is delayed
      or reduced by the injection of quetiapine. These findings indicate that
      quetiapine affects the complex reactions related to activation of orexinergic
      system. Possible influences on the control of body weight and temperature are
      discussed.

PMID- 17010429
TI  - Somatostatin receptors in wildtype and somatostatin deficient mice and their
      involvement in nitric oxide physiology in the retina.
AB  - The present study investigated the localization and density of somatostatin
      (SRIF) receptor subtypes (sst(1-5)) and SRIF-nitric oxide (NO()) interactions in
      the retina of wildtype [WT, (+/+)] and somatostatin deficient mice [SRIF (-/-)].
      Immunohistochemistry and radioligand binding studies with subsequent
      autoradiography were performed. Monoclonal antibodies [SRIF, protein kinase C
      (rod bipolar cells marker), microtubule associated protein 1A (ganglion cell
      marker)] and polyclonal antibodies (anti-sst(1), sst(2A), sst(4) receptor) were
      applied to 10-14 microm sections of retinas fixed in paraformaldehyde. NADPH
      diaphorase reactivity was assessed histochemically. [(125)I]LTT SRIF-28 alone or
      in the presence of MK678 (sst(2) agonist) and [(125)I]Tyr(3)-octreotide were
      employed to quantify sst(1-5), sst(1/4)and sst(2/5) receptor densities,
      respectively. sst(1), sst(2A), and sst(4) receptor immunoreactivities were
      observed in processes of the inner plexiform layer (IPL), rod bipolar, and in
      ganglion cells and processes, respectively, in WT and SRIF (-/-) mice. Specific
      [(125)I]LTT SRIF-28 and [(125)I]Tyr(3)-octreotide binding was increased
      significantly in SRIF (-/-) mice. NADPH-diaphorase staining was localized in
      photoreceptors and amacrine cells, but not rod bipolar and ganglion cells. Also,
      NADPH-diaphorase staining was not colocalized with sst(1), sst(2A) or sst(4)
      receptor immunoreactivity. These results demonstrate an upregulation of SRIF
      receptors in mice lacking SRIF, but no evident SRIF-NO(*) interaction was
      observed in the mouse retina.

PMID- 17010431
TI  - Systemic antineutrophil cytoplasmic antibody vasculitis in a patient with chronic
      lymphocytic leukemia: quite a rare diagnosis.
AB  - There might be rheumatic manifestations of malignant diseases, especially those
      of the hematological type. Until now, antineutrophil cytoplasmic antibody (ANCA)
      associated vasculitis in chronic lymphocytic leukemia (CLL) has been reported on
      only very few occasions. Here, we present our patient with Rai stage II CLL who
      came to us with constitutional symptoms. She turned out to have hematuria with
      dysmorphic erythrocytes and developed hemoptysis. She had pulmonary-renal
      syndrome and was diagnosed with p-ANCA positive microscopic polyangiitis. She is
      currently using prednisolone and cyclophosphamide and undergoing regular
      hemodialysis. Constitutional symptoms in patients with hematological malignancies
      should make the physicians consider systemic vasculitis after exclusion of
      disease-related complications.

PMID- 17010430
TI  - Late onset aplastic anemia during treatment of chronic myeloid leukemia with
      imatinib mesylate.

PMID- 17010432
TI  - Open forum--Are myelodysplastic syndromes cancer? Response to Dr. Steensma.

PMID- 17010433
TI  - Ultra high platelet count might be a characteristic feature of chronic myeloid
      leukemia rather than essential thrombocythemia.

PMID- 17010434
TI  - Is intestinal diffuse large b cell lymphoma a relatively benign disease?

PMID- 17010435
TI  - Attitudes of Turkish parents, pediatric residents, and medical students toward
      child disciplinary practices.
AB  - OBJECTIVE: The aims of the study were to: determine the attitudes of parents,
      pediatric residents, and medical students from a Turkish population toward
      childhood disciplinary methods; ascertain the association of participants'
      abusive childhood history with their attitudes toward discipline; and assess
      their attitudes about disciplinary actions, which should be reported as abuse.
      METHOD: A cross-sectional survey was conducted in Ankara University School of
      Medicine, Department of Social Pediatrics. Sixty-five parents, 39 pediatric
      residents, and 106 medical students completed a questionnaire (Survey of
      Standards of Discipline). This questionnaire was designed to measure
      sociodemographic characteristics, attitudes toward childhood disciplinary
      practices, and abusive childhood experiences. There were 43 different
      disciplinary acts in this questionnaire. The participants were expected to give
      responses to these acts in three categories: (a) acceptable as discipline; (b)
      unacceptable as discipline; and (c) unacceptable as discipline-would report to
      authorities as child abuse. Based on the responses to this questionnaire, we
      developed the Severity Scale. Using this scale, physical severity scores, verbal
      severity scores, and total severity scores were measured for each participant.
      RESULTS: None of the participants accepted life-threatening practices as
      discipline, but some declared certain abusive disciplinary practices as
      acceptable. Some forceful disciplinary methods were not considered as reportable
      by participants. All severity scores of both residents and students were found to
      be higher than those of the parents (for verbal severity scores p=.042). Also,
      both verbal and physical severity scores of parents with one child were higher
      than those of parents with two children (for verbal severity scores p=.044).
      Ninety-one participants (43.3%) indicated that beating was an acceptable form of
      discipline. Of parents, 66.9% reported abusive childhood history by their own
      criteria. Of medical students with an abusive childhood experience, 56.5%
      accepted beating as appropriate (p=.001). Both verbal and physical severity
      scores were found to be higher in participants with abusive childhood history.
      CONCLUSIONS: Abusive childhood history and lack of education regarding
      appropriate discipline techniques are linked to the acceptance of certain
      physical discipline practices. Turkey's cultural and traditional norms may be
      associated with the use of physical punishment, and in some cases, physical
      abuse. The lack of awareness of abusive discipline methods among physicians
      constitutes problems for child protection and must be addressed. Thus,
      educational programs on child disciplinary practices are required to provide an
      increased awareness of child abuse among health professional trainees and parents
      in Turkey.

PMID- 17010436
TI  - Physical punishment, childhood abuse and psychiatric disorders.
AB  - OBJECTIVES: Physical punishment, as a means of disciplining children, may be
      considered a mild form of childhood adversity. Although many outcomes of physical
      punishment have been investigated, little attention has been given to the impact
      of physical punishment on later adult psychopathology. Also, it has been stated
      that physical punishment by a loving parent is not associated with negative
      outcomes; however, this theory has not been empirically tested with regard to
      psychiatric disorders. The main objective of the present study was to investigate
      three categories of increasing severity of childhood adversity (no physical
      punishment or abuse, physical punishment only, and child abuse) to examine
      whether the childhood experience of physical punishment alone was associated with
      adult psychopathology, after adjusting for sociodemographic variables and
      parental bonding dimensions. METHODS: Data were drawn from the nationally
      representative National Comorbidity Survey (NCS, n=5,877; age 15-54 years;
      response rate 82.4%). Binary logistic and multinomial logistic regression models
      were used to determine the odds of experiencing psychiatric disorders. RESULTS:
      Physical punishment was associated with increased odds of major depression
      (AOR=1.22; 95% CI=1.01-1.48), alcohol abuse/dependence (AOR=1.32; 95% CI=1.08
      1.61), and externalizing problems (AOR=1.30; 95% CI=1.05-1.60) in adulthood after
      adjusting for sociodemographic variables and parental bonding dimensions.
      Individuals experiencing physical punishment only were at increased odds of adult
      psychopathology compared to those experiencing no physical punishment/abuse and
      at decreased odds when compared to those who were abused. CONCLUSIONS: Physical
      punishment is a mild form of childhood adversity that shows an association with
      adult psychopathology.

PMID- 17010437
TI  - Identifying the genetic determinants of emotionality in humans; insights from
      rodents.
AB  - The identification of human quantitative trait genes underlying variation in
      emotionality has proved to be both difficult and expensive. Whilst several QTL
      have been consistently identified and independently replicated across both
      phenotypes and populations, little progression has been made towards the
      identification of underlying genes or even variants. In this review we discuss
      the potential for using cross-species QTL concordance as a tool for QTL
      dissection in behaviour genetics, using an affect-related locus mapped to human
      chromosome 1 as an example.

PMID- 17010438
TI  - Increased ethanol intake after prenatal ethanol exposure: studies with animals.
AB  - This review analyses the most relevant studies in which ethanol intake was
      measured after prenatal exposure to the drug. Despite the variety in methodology,
      in most such studies this prenatal experience induced a higher consumption of
      ethanol. Several variables that may affect the expression of this phenomenon are
      discussed, such as gender, age at testing, period of ethanol exposure, ethanol
      dose and conditions during the test. The mechanisms proposed in all these studies
      to explain the increased ethanol intake effect are also discussed. Some of these
      mechanisms are related to the teratological effects of the drug on the
      neurochemical systems involved in the reinforcing effects of abuse drugs, as well
      as on the regulatory systems of stress response. Another explanation of this
      phenomenon is also proposed in terms of associative learning. Specifically, the
      increased ethanol intake effect may be the result of a conditioned preference for
      ethanol acquired by the fetus when exposed to the drug during the last days of
      gestation.

PMID- 17010439
TI  - Environmental challenge vis a vis opportunity: the case of water hyacinth.
AB  - Water hyacinth (Eichhornia crassipes) is a noxious weed that has attracted
      worldwide attention due to its fast spread and congested growth, which lead to
      serious problems in navigation, irrigation, and power generation. On the other
      hand, when looked from a resource angle, it appears to be a valuable resource
      with several unique properties. As a result, research activity concerning control
      (especially biological control) and utilization (especially wastewater treatment
      or phytoremediation) of water hyacinth has boomed up in the last few decades.
      Investigations on biogas/compost production from water hyacinth have also come up
      very well mainly from few research groups in India. This review presents a
      comprehensive view of the research related to water hyacinth with special
      emphasis on the recent investigations on water hyacinth control and utilization
      technologies conducted in the last 2-3 decades. Based on these significant
      research achievements, now it is desirable to identify a management strategy so
      that the excessive growth can be controlled and the plant can be used in
      beneficial ways. In the rural areas, water hyacinth could be used in an
      integrated manner for decentralized wastewater treatment systems coupled to
      biogas and compost production from the resulting biomass. There is a need to work
      out the techno-economic viability of such integrated model systems.

PMID- 17010440
TI  - Inhibition of aldehyde detoxification in CNS mitochondria by fungicides.
AB  - Among the several converging factors leading to Parkinson's disease,
      epidemiological studies indicate a correlation between Parkinson's disease (PD)
      with living in a rural area and/or exposure to agricultural pesticides. In this
      present study, we examined the potential of multiple agricultural pesticides for
      their ability to inhibit the function of whole, respiring rat brain mitochondria
      using the oxidation of the neurotoxic lipid-aldehyde trans-4-hydroxy-2-nonenal
      (HNE) as a biomarker for mitochondrial aldehyde dehydrogenase (ALDH) activity in
      situ. We chose an arbitrary cutoff concentration of 10 microM of each pesticide.
      Our data demonstrate that only four of the eighteen compounds tested inhibited
      oxidation of HNE to trans-4-hydroxy-2-nonenoic acid (HNEAcid). These compounds
      included rotenone, maneb, mancozeb, and benomyl. Surprisingly, maneb, mancozeb,
      and benomyl did not inhibit mitochondrial respiration but inhibited the activity
      of purified rat ALDH2 and rat ALDH5A, enzymes found in brain mitochondria that
      oxidize HNE and aldehydes derived from neurotransmitters. Our data demonstrate
      that mitochondrial ALDHs are sensitive targets of pesticide inactivation and that
      pesticides such as maneb and benomyl can decrease the detoxification of lipid
      peroxidation derived aldehydes such as HNE and, likely, aldehydes derived from
      neurotransmitters.

PMID- 17010441
TI  - Synthesis, characterization and studies on DNA-binding of a new Cu(II) complex
      with N1,N8-bis(l-methyl-4-nitropyrrole-2-carbonyl)triethylenetetramine.
AB  - A new Cu(II) complex of CuLCl(2) (here, L=N(1),N(8)-bis(1-methyl-4-nitropyrrole-2
      carbonyl)triethylenetetramine) had been synthesized and characterized. The
      structure of the complex was investigated with density functional theory (DFT)
      calculations. DNA-binding of the Cu(II) complex and its effects on tumor cell
      viability were firstly studied. The interactions between the complex and calf
      thymus DNA had been investigated using UV spectra, fluorescent spectra, viscosity
      and CV (cyclic voltammetry). The cleavage reaction on plasmid DNA has been
      monitored by agarose gel electrophoresis. The experimental results show that the
      mode of binding of the complex to DNA is classical intercalation and the complex
      can cleave pBR322 DNA. The effects of the CuL on cell viability were tested using
      the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) dye assay
      and the results indicate that the CuL had certain effect on cancer cells.

PMID- 17010443
TI  - Differentiating antidepressants of the future: efficacy and safety.
AB  - There have been significant advances in the treatment of depression since the
      serendipitous discovery that modulating monoaminergic neurotransmission may be a
      pathological underpinning of the disease. Despite these advances, particularly
      over the last 15years with the introduction of selective serotonin and/or
      norepinephrine reuptake inhibitors (SNRI), there still remain multiple unmet
      clinical needs that would represent substantial improvements to current treatment
      regimens. In terms of efficacy there have been improvements in the percentage of
      patients achieving remission but this can still be dramatically improved and, in
      fact, issues still remain with relapse. Furthermore, advances are still required
      in terms of improving the onset of efficacy as well as addressing the large
      proportion of patients who remain treatment resistant. While this is not well
      understood, collective research in the area suggests the disease is heterogeneous
      in terms of the multiple parameters related to etiology, pathology and response
      to pharmacological agents. In addition to efficacy further therapeutic advances
      will also need to address such issues as cognitive impairment, pain, sexual
      dysfunction, nausea and emesis, weight gain and potential cardiovascular effects.
      With these unmet needs in mind, the next generation of antidepressants will need
      to differentiate themselves from the current array of therapeutics for
      depression. There are multiple strategies for addressing unmet needs that are
      currently being investigated. These range from combination monoaminergic
      approaches to subtype selective agents to novel targets that include mechanisms
      to modulate neuropeptides and excitatory amino acids (EAA). This review will
      discuss the many facets of differentiation and potential strategies for the
      development of novel antidepressants.

PMID- 17010444
TI  - BMI, sex, and antidepressant response.
AB  - BACKGROUND: Investigators have examined potential mechanisms for the observed
      differences between men and women in antidepressant response. However, to date no
      studies have measured the impact of body mass index (BMI) on men's and women's
      response to selective serotonin re-uptake inhibitors or placebo. METHODS: We
      evaluated the response to antidepressants and placebo of 274 non-obese (BMI<30)
      and obese (BMI>30) depressed outpatients participating in Phase II-IV clinical
      trials. After categorizing men and women into their respective BMI groups, we
      measured the amount of change each group experienced from baseline to the final
      visit using the HAM-D-17 and MADRS ratings scales. RESULTS: Compared to women,
      men assigned to an antidepressant had a significantly lower mean total change on
      both the HAM-D-17 [non-obese, F(1,88)=5.292, p=0.024; obese, F(1,39)=7.040;
      p=0.012] and the MADRS [non-obese, F(1,66)=4.049, p=0.048; obese, F(1,27)=8.631,
      p=0.007]. In fact, obese men showed the smallest difference in antidepressant
      placebo response. The results of the ANCOVAs indicated significant main effects
      of treatment (placebo vs. antidepressant), sex of the patient, and BMI category
      as well as a significant interaction between all three variables. LIMITATIONS:
      Patients participating in clinical trials are not necessarily representative of
      the entire depressed population. In addition, our results include only SSRIs, not
      other antidepressants. CONCLUSION: Compared to the rest of the depressed sample
      the subgroup of depressed obese men (n=40) showed little or no therapeutic
      benefit with SSRI antidepressants. Although our findings may have important
      clinical implications, replication and further research is warranted in order to
      understand their underlying mechanisms and their pertinence to dosing strategies.

PMID- 17010445
TI  - Impaired decision-making in suicide attempters may increase the risk of problems
      in affective relationships.
AB  - BACKGROUND: Decision-making has been found to be altered in suicide attempters
      and may represent a neuropsychological trait of vulnerability to suicidal
      behaviour. Environmental stressors such as adverse life events and interpersonal
      problems have been demonstrated to precipitate suicidal acts in vulnerable
      people. However, the link between vulnerability and stressors is complex and may
      even be circular. In the present study, we hypothesized that impaired decision
      making may be associated with an increased risk of negative life events in
      suicide attempters. METHODS: Forty-eight patients with a history of attempted
      suicide were assessed with the Iowa Gambling Task and interviewed regarding life
      events experienced over the past 12 months. RESULTS: Decision-making performance
      was negatively correlated with interpersonal difficulties in the affective-
      namely marital and family--domain (rs=-0.39, p=0.006) but not with interpersonal
      difficulties in other social contexts, stressful life events or somatic health
      problems. LIMITATIONS: The relatively small sample size and the use of non
      parametric methods may lead to a risk of type II errors. Furthermore, data on
      life events were retrospectively collected. CONCLUSIONS: Altered decision-making
      may increase the risk of problematic affective relationships. These results
      underline the complex and possibly reciprocal link between environmental stress
      factors and cognitive vulnerability traits. This could be useful for the design
      of intervention strategies for suicidal behaviour.

PMID- 17010446
TI  - RETRACTED: Doxycycline alters the expression of matrix metalloproteases in the
      endometrial cells exposed to ovarian steroids and pro-inflammatory cytokine.
AB  - This article has been retracted: please see Elsevier Policy on Article Withdrawal
      (https://www.elsevier.com/about/our-business/policies/article-withdrawal).This
      article has been retracted at the request of the Editors following an
      investigation by the Office of Research Integrity (ORI) at the Department of
      Health and Human Services. The investigation confirmed that the data presented
      has been falsified by the last author.

PMID- 17010447
TI  - Differential cellular expression of LIGHT and its receptors in early gestation
      human placentas.
AB  - LIGHT (homologous to lymphotoxins, exhibits inducible expression, competes with
      herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T
      lymphocytes) is an apoptosis-inducing member of the tumor necrosis factor family
      of ligands. Messenger RNAs encoding LIGHT and its receptors, lymphotoxin-beta
      receptor (LTbetaR), decoy receptor-3 (DcR3) and herpes virus entry mediator
      (HVEM), are present in first trimester and term placentas. Proteins have been
      localized to specific cells in term but not earlier gestation placentas. Here, we
      have studied LIGHT and its receptors in early (6-7 weeks) and early-to-middle (8
      13 weeks) gestation using immunohistology. Notable cell-specific, gestation
      related features were identified. LIGHT and two of its receptors, a membrane
      bound receptor that mediates apoptosis (LTbetaR) and a soluble receptor that
      interferes with LIGHT signaling (DcR3), were present in syncytiotrophoblast and
      cytotrophoblast cells in all samples but were detected in placental stromal cells
      only at week 8 and thereafter. HVEM, a membrane-bound receptor that protects
      against apoptosis, was expressed only on syncytiotrophoblast. These observations
      suggest that the LIGHT system may regulate early to middle stages of placental
      development via cell-specific, temporally programmed expression of the ligand and
      its receptors, and may also assist in preserving placental immune privilege.

PMID- 17010449
TI  - Cytochrome c oxidase mRNA as an internal control for detection of Potato virus Y
      and Potato leafroll virus from single aphids by a co-amplification RT-PCR assay.
AB  - Using cytochrome c oxidase subunit 1 (COX1) mRNA as the internal control, a
      triplex reverse transcription-polymerase chain reaction (RT-PCR) for detection of
      Potato virus Y (PVY) and Potato leafroll virus (PLRV) with co-amplification of
      COX1 from single specimens of various aphid species has been developed. Partial
      length cDNA of COX1 from green peach aphid, Myzus persicae (Sulzer), potato
      aphid, Macrosiphum euphorbiae (Thomas), buckthorn aphid, Aphis nasturtii
      (Kaltenbach), and pea aphid, Acyrthosiphom pisum (Harris), was cloned and
      sequenced. These sequences, together with existing COX1 sequences from other
      aphid species capable or suspected to be capable of transmitting PVY and/or PLRV,
      were analyzed. The sequence identity between any two aphid species ranged from 97
      to 100% at the putative protein level, and 89 to 94% at the nucleic acid level.
      Two highly conserved COX1 nucleotide sequence stretches were selected to design
      universal primers Aph F and Aph R. This primer pair, together with two existing
      universal primer pairs (C1-J-2183 and C1-N-2329; Favret F and Favret R), were
      evaluated at the optimal annealing temperature using RNA from M. persicase, M.
      euphorbiae, and A. nasturtii. The Aph primer pair performed well in the monoplex
      RT-PCR but poorly in the triplex RT-PCR in the presence of the PVY- and PLRV
      specific primers. On the other hand, the Favret and C1 primer pairs performed
      well in both monoplex and triplex RT-PCR formats using single aphids of M.
      persicase, M. euphorbiae and A. nasturtii, demonstrating their suitability to
      indicate the successfulness of RT-PCR assays for PVY and PLRV. Using the Favret,
      PVY and PLRV primer sets, single aphids of M. persicase, M. euphorbiae and A.
      nasturtii that had been exposed to PLRV-infected and/or PVY-infected potato
      plants were assessed for their acquisition of the viruses by the triplex RT-PCR
      assay. Although majority (175/180) of the aphid samples produced the COX1
      fragment, five aphid samples failed to produce either the COX1- or the virus
      specific band, indicating failed RT-PCR in these samples. This method offers a
      sensitive tool for detection of viruliferous aphids combined to an effective
      quality control measure.

PMID- 17010448
TI  - Treatment adherence among patients with schizophrenia treated with atypical and
      typical antipsychotics.
AB  - This study evaluated treatment adherence among patients with schizophrenia
      receiving atypical and typical antipsychotics. Claims data for 7017 treatment
      episodes of commercially insured patients with schizophrenia (ICD-9-CM) receiving
      antipsychotics, covering the period from January 1999 through August 2003, were
      assessed. Overall adherence was evaluated by adherence intensity (medication
      possession ratio) and treatment duration (length of treatment episode). Pair-wise
      comparisons of the individual atypicals and a combined group of leading typical
      antipsychotics were undertaken using multiple regression, adjusting for differing
      patient characteristics. Each atypical antipsychotic demonstrated a significantly
      higher adherence intensity than the combined typicals, while quetiapine
      demonstrated a significantly greater adherence intensity than risperidone and
      olanzapine. None of the atypicals showed treatment durations significantly
      different from the typicals. While the small improvements in adherence intensity
      among atypical agents do not appear to be clinically important, they may reflect
      an underlying, stronger tendency to use filled prescriptions.

PMID- 17010450
TI  - Intrathecal administration of yohimbine impairs locomotion in intact rats.
AB  - The effects of upper lumbar level intrathecal injection of yohimbine, an alpha2
      noradrenergic antagonist, on overground locomotion in intact rats was studied.
      This treatment caused dose-dependent impairment of hindlimb locomotor movement,
      which varied from transient hindlimb paralysis at a dose of 200 microg/20 microl
      to transient trunk instability at 50 microg/20 microl. Repetitive (every 48 h)
      injections of yohimbine at high (200 microg/20 microl) and medium (100 microg/20
      microl) doses caused tachyphylaxis, which usually led to a lack of reaction to
      the third injection. This phenomenon was not observed after repetitive injections
      of the low (50 microg/20 microl) dose of the drug. These results show that the
      noradrenergic system is involved in the control of locomotion, since intrathecal
      administration of a specific antagonist affects this activity in intact rats.

PMID- 17010451
TI  - Involvement of specific orexigenic neuropeptides in sweetener-induced
      overconsumption in rats.
AB  - Palatability is one of the factors that regulates food and fluid intake and
      contributes to overconsumption in turn contributing to obesity. To elucidate the
      brain mechanisms of the palatability-induced ingestion, we explored the roles of
      six hypothalamic orexigenic neuropeptides, orexin, melanin-concentrating hormone
      (MCH), neuropeptide Y (NPY), agouti-related protein (AgRP), ghrelin and
      dynorphin, in the intake of a palatable solution, saccharin. Of the six peptides,
      intracerebroventricular (i.c.v.) administrations of orexin, MCH and NPY increased
      the intake of saccharin. Drinking of saccharin in turn elevated the mRNA levels
      of orexin and NPY, but not MCH. Pre-treatments of naloxone, an opioid antagonist,
      blocked the orexigenic effects of orexin and NPY. Specific gastric motor
      responses induced by central orexin-A and NPY are well known, however, MCH did
      not induce such responses. The i.c.v. administration of orexin-A facilitated
      gastric emptying. These results suggest that the overconsumption promoted by
      sweet and palatable tastes is attributed to the activation of orexigenic
      neuropeptides, such as orexin and NPY, and a downstream opioid system together
      with enhanced digestive functions.

PMID- 17010452
TI  - Effects of Cylindrospermopsis raciborskii and Aphanizomenon ovalisporum
      (cyanobacteria) ingestion on Daphnia magna midgut and associated diverticula
      epithelium.
AB  - This article reports a light and electron microscopy investigation of the effects
      of Cylindrospermopsis raciborskii and Aphanizomenon ovalisporum ingestion on
      midgut and associated digestive diverticula of Daphnia magna. Additionally,
      survivorship and growth effects caused by feeding on cyanobacteria were assessed.
      Three cyanobacteria were used in the experiments: cylindrospermopsin (CYN)
      producing C. raciborskii, CYN-producing A. ovalisporum and non-CYN-producing C.
      raciborskii. In order to discriminate between the alterations due to the low
      nutritional value of cyanobacteria and toxic effects, a control group was fed on
      the chlorophyte Ankistrodesmus falcatus and another control group was not fed. In
      the chlorophyte fed control, the epithelium lining the midgut and associated
      diverticula is mainly formed by strongly stained cells with an apical microvilli
      border. Nevertheless, unstained areas in which cell lyses had occurred were also
      observed. In the unfed control, the unstained areas became predominant due to an
      increment of cell lyses. All individuals fed on CYN-producing A. ovalisporum and
      some of those fed on non-CYN-producing C. raciborskii appear similar to the unfed
      control. However, some individuals fed on non-CYN-producing C. raciborskii showed
      similarities with the fed control. In contrast, the midgut and digestive
      diverticula of D. magna fed on CYN-producing C. raciborskii showed a widespread
      dissociation of epithelial cells, associated with severe intracellular
      disorganization, but cell lysis was less evident than in controls. These
      alterations cannot be attributed to CYN, because those effects were not induced
      by CYN-producing A. ovalisporum. Therefore, data suggest the production of
      another unidentified active metabolite by CYN-producing C. raciborskii,
      responsible for the disruption of cell adhesion in the epithelium of D. magna
      digestive tract. Data also show that the tested cyanobacteria are inadequate as
      food to D. magna, due to low nutritional value and toxic content.

PMID- 17010453
TI  - Post-translational modifications of Trypanosoma cruzi histone H4.
AB  - Histone tails provide sites for a variety of post-translational modifications
      implicated in the control of gene expression and chromatin assembly. As both
      histones and control of gene expression in trypanosomes are highly divergent
      compared to most eukaryotes, post-translational modifications of Trypanosoma
      cruzi histones were investigated. After in vivo incubation of live parasites with
      radiolabeled precursors, histone H4 mainly incorporates [(3)H]-acetyl, and to a
      lesser extent [(3)H]-methyl residues. In contrast, histone H3 preferentially
      incorporates [(3)H]-methyl residues. The modifications of histone H4 were further
      characterized by mass spectrometry. MALDI-TOF-TOF-MS analysis revealed that
      peptides from histone H4 amino-terminus, obtained by either endoproteinase Glu-C
      or endoproteinase Arg-C digestion, contain isoforms with 14 and 42Da additions,
      suggesting the presence of simultaneous acetylations and/or methylations. Tandem
      mass spectrometry analysis demonstrated that the N-terminal alanine is
      methylated, and lysine residues at positions 4, 10, 14 and 57 are acetylated;
      lysine at position 18 is mono-methylated, while arginine at position 53 is
      dimethylated. Immunoblotting analyses using specific antibodies raised against
      synthetic and acetylated peptides of T. cruzi histone H4 indicate that lysine 4
      is acetylated in the majority of histone H4, while other acetylations at the N
      terminus portion of histone H4 are less abundant.

PMID- 17010454
TI  - Abundance of intrinsically unstructured proteins in P. falciparum and other
      apicomplexan parasite proteomes.
AB  - Preliminary sequence analysis of Plasmodium falciparum has shown that the
      proteome of this organism is enriched in intrinsically unstructured proteins
      (IUPs), which are either completely disordered or contain large disordered
      regions. IUPs have been characterized as a unique class of proteins that plays an
      important role in biology and disease. In this study, the IUP contents in the
      proteomes of apicomplexan parasites, especially the proteome of P. falciparum and
      its various life cycle stages, have been evaluated with DisEMBL-1.4. Compared
      with other proteomes, apicomplexan species are extremely abundant in proteins
      containing long disordered regions, and the IUP contents in mammalian Plasmodium
      species are higher than in most other apicomplexan parasites. The proteome of the
      P. falciparum sporozoite appears to be distinct from the other life cycle stages
      in having an even higher content of disordered proteins. The abundance of IUPs in
      the P. falciparum proteome correlates with its enrichment in repetitive
      sequences. The structural plasticity of IUPs, which allows promiscuous binding
      interactions, may favour parasite survival both by inhibiting the generation of
      effective high affinity antibody responses and by facilitating the interactions
      with host molecules necessary for attachment and invasion of host cells.

PMID- 17010455
TI  - Recognition of the tumor suppressor protein p53 and other protein targets by the
      calcium-binding protein S100B.
AB  - S100B is an EF-hand containing calcium-binding protein of the S100 protein family
      that exerts its biological effect by binding and affecting various target
      proteins. A consensus sequence for S100B target proteins was published as
      (K/R)(L/I)xWxxIL and matches a region in the actin capping protein CapZ (V.V.
      Ivanenkov, G.A. Jamieson, Jr., E. Gruenstein, R.V. Dimlich, Characterization of S
      100b binding epitopes. Identification of a novel target, the actin capping
      protein, CapZ, J. Biol. Chem. 270 (1995) 14651-14658). Several additional S100B
      targets are known including p53, a nuclear Dbf2 related (NDR) kinase, the RAGE
      receptor, neuromodulin, protein kinase C, and others. Examining the binding sites
      of such targets and new protein sequence searches provided additional potential
      target proteins for S100B including Hdm2 and Hdm4, which were both found to bind
      S100B in a calcium-dependent manner. The interaction between S100B and the Hdm2
      and/or the Hdm4 proteins may be important physiologically in light of evidence
      that like Hdm2, S100B also contributes to lowering protein levels of the tumor
      suppressor protein, p53. For the S100B-p53 interaction, it was found that
      phosphorylation of specific serine and/or threonine residues reduces the affinity
      of the S100B-p53 interaction by as much as an order of magnitude, and is
      important for protecting p53 from S100B-dependent down-regulation, a scenario
      that is similar to what is found for the Hdm2-p53 complex.

PMID- 17010456
TI  - The ins and outs of peroxisomes: co-ordination of membrane transport and
      peroxisomal metabolism.
AB  - Peroxisomes perform a range of metabolic functions which require the movement of
      substrates, co-substrates, cofactors and metabolites across the peroxisomal
      membrane. In this review, we discuss the evidence for and against specific
      transport systems involved in peroxisomal metabolism and how these operate to co
      ordinate biochemical reactions within the peroxisome with those in other
      compartments of the cell.

PMID- 17010457
TI  - Cardiac syndrome X versus metabolic syndrome X.

PMID- 17010458
TI  - Cardiac troponin I release in non-ischemic reversible myocardial injury from
      parvovirus B19 myocarditis.
AB  - Cardiac troponin I is released from myocytes in both reversible and irreversible
      myocardial injury. The changes in myocyte membrane permeability resulting from
      the injury could be enough for the release of cardiac troponins from the free
      cytosolic pool of myocytes without structural damage. We report a case of
      parvovirus B19 myocarditis in a 26-year-old male who developed regional wall
      motion abnormalities and severe left ventricular systolic dysfunction with
      elevated serum levels of cardiac troponin I (peak=11.7 ng/ml). Diagnosis of
      parvovirus myocarditis was confirmed by presence of high titers of parvovirus B19
      IgG and identification of parvovirus B19 DNA by polymerase chain reaction. Within
      a few days of supportive treatment, the regional wall motion abnormalities
      resolved, the cardiac function recovered, and the elevation in serum cardiac
      troponin I subsided. This case further denotes the possibility of release of
      cardiac troponin I in non-ischemic, reversible myocardial injury.

PMID- 17010459
TI  - Why do women participate in the English cervical cancer screening programme?
AB  - The vast majority of women in England attend for cervical cancer screening.
      Conventional economic theorising fails to explain why and its predictions are
      inconsistent with the evidence. Using questionnaire data, we analyse directly
      motivations for screening attendance. We conclude that regular attendance at
      screening is driven primarily by a search for reassurance, a sense of duty and
      herd signalling. It is evident that recognisable sub-groups of attenders exist,
      in which the configurations of motivational factors differ. Being motivated to
      attend by physicians is less significant that is widely supposed and is more
      frequently associated with irregular attendance.

PMID- 17010460
TI  - Adhesion of Yersinia enterocolitica to non-cultured epithelial cells from pig and
      rabbit ilea.
AB  - A simple and reliable method was developed to isolate intact epithelial cells
      from pig and rabbit ilea and these were used to investigate the adhesion of
      Yersinia enterocolitica. Hydrophobic interaction was eliminated by treating the
      bacterial culture with 0.8 M tetramethyl urea (TMU). Virulent strains of Y.
      enterocolitica had significantly greater attachment than avirulent strains but
      both attached in a linear dose-dependant fashion. Epithelial cells prepared from
      pig ilea were attached to more readily than those prepared from rabbit ilea.

PMID- 17010461
TI  - A TaqMan polymerase chain reaction method for monitoring RDX-degrading bacteria
      based on the xplA functional gene.
AB  - Hexahydro-1,3,5-trinitro-1,3,5,-triazine (RDX) is a cyclic nitramine explosive
      that is a major component in many military high-explosive formulations. In this
      study, we developed a real-time TaqMan polymerase chain reaction (PCR) that
      targets the xplA functional gene involved in the breakdown/transformation of RDX.
      The xplA gene, described previously [Seth-Smith, H.M., Rosser, S.J., Basran, A.,
      Travis, E.R., Dabbs, E.R., Nicklin S., Bruce, N.C., 2002. Cloning, sequencing,
      and characterization of the hexahydro-1,3,5-trinitro-1,3,5-triazine degradation
      gene cluster from Rhodococcus rhodochrous. Appl. Environ. Microbiol. 68, 4764
      4771.], was isolated from Rhodococcus rhodochrous 11Y and codes for a fused
      flavodoxin-cytochrome P450 protein. We applied the xplA TaqMan PCR assay to
      detect and monitor strain 11Y in soil microcosms that had been amended with
      strain 11Y and RDX as well as soil microcosms in which soils had been subjected
      to heat-sterilization prior to the addition of strain 11Y and RDX. The
      specificity of the assay was tested against a number of genomic bacterial
      templates and surprisingly found to cross react with other RDX degrading
      bacteria. Two of these strains, Gordonia sp. KTR9 and Williamsia sp. KTR4, were
      previously isolated in our laboratory and were not known to possess xplA
      homologs. Southern blot analysis confirmed the presence of xplA gene homologs in
      both of these strains. The sensitivity of the xplA TaqMan PCR primer/probes set
      was evaluated using 11Y cell standards as well as 11Y cell standards spiked in
      soils that mimicked conditions found in the experimental soil microcosms. While
      the assay was found to be linear over a range of 6 orders of magnitude for both
      sets of standards, sensitivity of the assay was reduced between one and two logs
      for cells spiked in soil. The capacity to monitor the presence of specific
      microorganisms and/or genes coding enzymes involved in RDX
      transformation/breakdown in complex environmental samples will be critical for
      bioremediation strategies targeting explosives that rely on in situ
      bioaugmentation and monitored natural attenuation.

PMID- 17010462
TI  - The effect of caffeine on handwriting movements in skilled writers.
AB  - In laboratory tasks, caffeine has been shown to improve psychomotor performance.
      The aim of the present experiment was to assess the effects of caffeine on a
      skilled everyday life task in habitual caffeine consumers. The assessment of
      handwriting movements of 20 adults was performed following the administration of
      0mg/kg (placebo), 1.5mg/kg, 3.0mg/kg or 4.5mg/kg of caffeine. A digitising tablet
      was used for the assessment of fine motor movements. Participants were asked to
      perform a simple writing task. Kinematic analysis of handwriting movements showed
      that, in comparison to placebo administration, high doses of caffeine (i.e.,
      4.5mg/kg) can produce improvements in handwriting as indicated by more fluent
      handwriting movements as well as an increase in maximum velocity and maximum
      positive and negative accelerations. The results suggest that higher doses of
      caffeine can enhance psychomotor performance.

PMID- 17010463
TI  - Listeria: A foodborne pathogen that knows how to survive.
AB  - The foodborne pathogen Listeria is the causative agent of listeriosis, a severe
      disease with high hospitalization and case fatality rates. Listeria monocytogenes
      can survive and grow over a wide range of environmental conditions such as
      refrigeration temperatures, low pH and high salt concentration. This allows the
      pathogen to overcome food preservation and safety barriers, and pose a potential
      risk to human health. This review focuses on the key issues such as survival of
      the pathogen in adverse environments, and the important adaptation and survival
      mechanisms such as biofilm formation, quorum sensing and antimicrobial
      resistance. Studies on the development of technologies to prevent and control L.
      monocytogenes contamination in foods and food processing facilities are also
      discussed.

PMID- 17010464
TI  - Vancomycin-resistant enterococci from animal sources in Korea.
AB  - Enterococci for which the minimum inhibitory concentration (MIC) of vancomycin
      was >/=8 mg/l were isolated from meat, feces, and raw milk samples collected in
      Korea from March to November 2003. Among the 243 vancomycin-resistant enterococci
      (VRE) that were identified the vanA vancomycin resistance gene was carried by 51
      Enterococcus faecium and one Enterococcus sp., vanC1 was carried by 151
      Enterococcus gallinarum, vanC2 was carried by 39 Enterococcus casseliflavus, and
      one Enterococcus sp. carried no van genes. Of the isolated enterococci carrying
      vanA, 4% were found to be highly resistant to gentamicin and 11% were resistant
      to ampicillin. Further genotyping of the E. faecium isolates carrying vanA using
      pulsed-field gel electrophoresis (PFGE) revealed extensive heterogeneity. The
      vancomycin resistance transferability test revealed that only two of the 52
      enterococci carrying the vanA gene were able to transfer vancomycin resistance to
      other enterococci. The VRE were recovered from various animal sources with a
      particularly high prevalence of E. faecium carrying the vanA gene being found in
      poultry meat.

PMID- 17010465
TI  - Cell bank characterization and fermentation optimization for production of
      recombinant heavy chain C-terminal fragment of botulinum neurotoxin serotype E
      (rBoNTE(H(c)): antigen E) by Pichia pastoris.
AB  - A process was developed for production of a candidate vaccine antigen,
      recombinant C-terminal heavy chain fragment of the botulinum neurotoxin serotype
      E, rBoNTE(H(c)) in Pichia pastoris. P. pastoris strain GS115 was transformed with
      the rBoNTE(H(c)) gene inserted into pHILD4 Escherichia coli-P. pastoris shuttle
      plasmid. The clone was characterized for genetic stability, copy number, and
      BoNTE(H(c)) sequence. Expression of rBoNTE(H(c)) from the Mut(+) HIS4 clone was
      confirmed in the shake-flask, prior to developing a fed-batch fermentation
      process at 5 and 19 L scale. The fermentation process consists of a glycerol
      growth phase in batch and fed-batch mode using a defined medium followed by a
      glycerol/methanol transition phase for adaptation to growth on methanol and a
      methanol induction phase resulting in the production of rBoNTE(H(c)). Specific
      growth rate, ratio of growth to induction phase, and time of induction were
      critical for optimal rBoNTE(H(c)) production and minimal proteolytic degradation.
      A computer-controlled exponential growth model was used for process automation
      and off-gas analysis was used for process monitoring. The optimized process had
      an induction time of 9 h on methanol and produced up to 3 mg of rBoNTE(H(c)) per
      gram wet cell mass as determined by HPLC and Western blot analysis.

PMID- 17010466
TI  - Involvement of nucleoprotein, phosphoprotein, and matrix protein genes of rabies
      virus in virulence for adult mice.
AB  - Rabies virus Ni-CE strain causes nonlethal infection in adult mice after
      intracerebral inoculation, whereas the parental Nishigahara strain kills mice. In
      this study, to identify viral gene(s) related to the difference in pathogenicity
      between Ni-CE and Nishigahara strains, we generated chimeric viruses with
      respective genes of the virulent Nishigahara strain in the background of the
      avirulent Ni-CE genome. Since chimeric viruses, which had the N, P, or M genes of
      the Nishigahara strain, respectively, killed adult mice after intracerebral
      inoculation, it became evident that the N, P, and M genes are related to the
      difference in pathogenicity between Ni-CE and Nishigahara strains. Previously, we
      showed that the G gene is a major contributor to the difference in pathogenicity
      between another avirulent strain, RC-HL, and the parental Nishigahara strain.
      These results imply that the attenuation mechanism of the Ni-CE strain is
      different from that of the RC-HL strain, thus suggesting that rabies virus can be
      attenuated by diverse mechanisms. This is the first report of changes in viral
      genes other than the G gene of rabies virus causing the reversion of
      pathogenicity of an avirulent strain.

PMID- 17010467
TI  - An attempt to directly trace polymeric nanoparticles in vivo with electron
      microscopy.
AB  - This work attempted to directly observe polymeric nanoparticles in vivo by
      analytical electron microscopy (AEM) using copper chlorophyll as the contrast
      agent, based on the experiments concerned with the copper chlorophyll labeled
      poly-DL-lactide nanoparticles and the in vivo distribution of the polysorbate 80
      (T-80)-coated nanoparticles in brain tissues. With the nanoprecipitation method
      without surfactants, copper chlorophyll is aggregated in the coordinately
      saturated form and encapsulated by the matrices of nanoparticles, which may
      ensure the stability of copper chlorophyll during the in vivo experiments. From
      both morphological information and chemical information, only the labeled
      nanoparticles with the T-80 coating were directly traced in the brain by AEM. The
      results not only support the mechanism of endocytosis and/or transcytosis of T-80
      coated nanoparticles targeted to the brain but also verify that it is practical
      to probe polymeric nanoparticles in vivo using AEM together with copper
      chlorophyll as the contrast agent.

PMID- 17010468
TI  - Influence of plasmid DNA topology on the transfection properties of DOTAP/DOPE
      lipoplexes.
AB  - Plasmid DNA (pDNA) can occur in the compact supercoiled (SC) form, the relaxed
      open circular (OC) form and the linearized form. In this paper we investigated
      the transfection efficiency of SC, OC and linearized pDNA complexed to DOTAP/DOPE
      liposomes in Vero cells. Only DOTAP/DOPE liposomes containing SC pDNA showed
      protein expression while DOTAP/DOPE liposomes loaded with OC or linearized pDNA
      failed. First we questioned if the better transfection properties of the SC pDNA
      containing lipoplexes could be due to a better transcription of SC pDNA in the
      nuclei of the cells, compared to OC and linearized pDNA. However, microinjecting
      (naked) SC, OC or linearized pDNA in the nuclei of the Vero cells revealed that
      the transcription efficiency was independent on the pDNA topology but did depend
      on the intranuclear concentration of the pDNA. As the amount of pDNA that reaches
      the nucleus is determined by the amount of pDNA that arrives in the cytosol it
      could be hypothesized that SC pDNA is more efficiently released from the
      DOTAP/DOPE liposomes when compared to OC and linearized pDNA. However,
      microinjecting comparable concentrations of the pDNA topologies in the cytoplasm
      still resulted in a significantly higher transfection in the case of SC pDNA,
      especially in cells that underwent cell division in the period after injection.
      It seems that, compared to OC and linearized pDNA, SC pDNA is better suited to
      reach the perinuclear region, a prerequisite to become entrapped in the nuclei of
      the cells during cell division.

PMID- 17010470
TI  - Prevalence of the metabolic syndrome in populations of Asian origin. Comparison
      of the IDF definition with the NCEP definition.
AB  - AIMS: To estimate the prevalence of the metabolic syndrome using the IDF versus
      NCEP definition. POPULATION: 14222 non-diabetic and 1516 diabetic subjects, aged
      25-74 years. RESULTS: The age-standardized prevalence of the IDF metabolic
      syndrome in non-diabetic men (women) was 12.0% (15.0%), 13.8% (2.5%), 12.8%
      (17.0%), and 13.2% (20.3%), respectively, in Chinese, Japanese, Mauritian
      Indians, and native Indians. The prevalence ratio of IDF to NCEP was 1.5 (1.5),
      2.7 (0.4), 1.2 (1.2), and 1.0 (1.3) in Chinese, Japanese, Mauritian, and Native
      Indian men (women), respectively. When the same obesity criteria for Japanese as
      for others were used the ratio for Japanese was 1.5 in both genders. Of all
      subjects fulfilling either of the two definitions, only 28% of men and 47% of
      women met the both. The prevalence of central obesity was 52 times greater using
      the IDF definition than using the NCEP definition in Japanese men but it was 0.8
      times lower in Japanese women. CONCLUSIONS: The IDF definition brought a higher
      prevalence of the metabolic syndrome than the NCEP in all except for Japanese
      women but many lean subjects with hypertension and/or dyslipidemia were
      undetected by this definition. The IDF criterion for central obesity for Japanese
      needs to be reconsidered.

PMID- 17010469
TI  - Elevated serum acylated (biologically active) ghrelin and resistin levels
      associate with pregnancy-induced weight gain and insulin resistance.
AB  - AIM: To study fasting biologically active serum ghrelin (RIA) and resistin
      (ELISA) levels in different trimesters of pregnancy (HP, n=45, 15 in each) and in
      gestational diabetes mellitus (GDM, n=30) compared to non-pregnant healthy women
      (NP, n=40) in correlation with TNF-alpha, soluble (s)TNF-receptor (R)-1, -2,
      leptin (ELISA), C-peptide (Cp, RIA) and Cp/blood glucose ratio (bg). STUDY
      DESIGN: Cross-sectional case control study. RESULTS: Acylated ghrelin levels were
      significantly increased (p<0.0001) in the 2nd (377+/-38pg/ml, X+/-S.D.) and
      decreased in the 3rd trimester (252+/-36) and in GDM (226+/-21) compared to NP
      controls (309+/-20) and HP women in the 1st trimester (314+/-41). Serum resistin
      levels were higher in the 1st (8.5+/-2.6ng/ml), 2nd (10.2+/-2.1) and 3rd (13.1+/
      3.6) trimesters of pregnancy and in GDM (15.7+/-3.5) than in NP controls (6.5+/
      2.3). Significant (p<0.01) negative linear correlations were found among fasting
      serum ghrelin and body mass index (BMI), the fasting C-peptide (Cp) level, C
      peptide/blood glucose (Cp/bg) ratio, TNF-alpha, soluble (s)TNFR-2, leptin and
      resistin concentrations in both, HP and GDM groups. Significant positive
      correlations were observed between serum acylated ghrelin and adiponectin, and
      between BMI and fasting Cp, Cp/bg, TNF-alpha, sTNFR-1, -2 and leptin levels in
      both pregnant groups. CONCLUSION: Increased fasting serum acylated ghrelin
      concentrations in the 2nd trimester may associate with weight gain during
      pregnancy. Hyperresistinemia may also be associated with the pregnancy-induced
      insulin resistance. A negative regulatory feed-back mechanism between resistin,
      TNF-alpha and ghrelin may be hypothesized.

PMID- 17010471
TI  - Different words, same meaning: understanding the languages of the genome.
AB  - There is undeniable value in using sequence comparison to identify putative
      regulatory sequences. However, a recent report has demonstrated that not all
      regulatory sequences are evolutionarily conserved. Cis-acting sequences around
      the RET gene, conserved in mammals but not in fish, are able to reproduce
      patterns of RET expression in zebrafish embryos. It is as yet unclear whether
      these sequences are 'below the radar' of current sequence alignment tools or
      whether their functional homology is not sequence based.

PMID- 17010472
TI  - Challenges and innovations in effective pulmonary systemic and macromolecular
      drug delivery.

PMID- 17010473
TI  - In vivo, in vitro and ex vivo models to assess pulmonary absorption and
      disposition of inhaled therapeutics for systemic delivery.
AB  - Despite the interest in systemic delivery of therapeutic molecules including
      macromolecular proteins and peptides via the lung, the accurate assessment of
      their pulmonary biopharmaceutics is a challenging experimental task. This article
      reviews in vivo, in vitro and ex vivo models currently available for studying
      lung absorption and disposition for inhaled therapeutic molecules. The general
      methodologies are discussed with recent advances, current challenges and
      perspectives, especially in the context of their use in systemic pulmonary
      delivery research. In vivo approaches in small rodents continue to be the
      mainstay of assessment by virtue of the acquisition of direct pharmacokinetic
      data, more meaningful when attention is given to reproducible dosing and control
      of lung-regional distribution through use of more sophisticated lung-dosing
      methods, such as forced instillation, microspray, nebulization and aerosol puff.
      A variety of in vitro lung epithelial cell lines models and primary cultured
      alveolar epithelial (AE) cells when grown to monolayer status offer new
      opportunity to clarify the more detailed kinetics and mechanisms of
      transepithelial drug transport. While continuous cell lines, Calu-3 and 16HBE14o
      , show potential, primary cultured AE cell models from rat and human origins may
      be of greater use, by virtue of their universally tight intercellular junctions
      that discriminate the transport kinetics of different therapeutic entities.
      Nevertheless, the relevance of using these reconstructed barriers to represent
      complex disposition of intact lung may still be debatable. Meanwhile, the
      intermediate ex vivo model of the isolated perfused lung (IPL) appears to resolve
      deficiencies of these in vivo and in vitro models. While controlling lung
      regional distributions, the preparation alongside a novel kinetic modeling
      analysis enables separate determinations of kinetic descriptors for lung
      absorption and non-absorptive clearances, i.e., mucociliary clearance,
      phagocytosis and/or metabolism. This ex vivo model has been shown to be
      kinetically predictive of in vivo, with respect to macromolecular disposition,
      despite limitations concerning short viable periods of 2-3 h and likely absence
      of tracheobronchial circulation. Given the advantages and disadvantages of each
      model, scientists must make appropriate selection and timely exploitation of the
      best model at each stage of the research and development program, affording
      efficient progress toward clinical trials for future inhaled therapeutic entities
      for systemic delivery.

PMID- 17010474
TI  - Gastro-intestinal metastasis of primary lung carcinoma: clinical presentations
      and outcome.
AB  - Symptomatic gastro-intestinal (GI) metastasis in lung carcinomas is extremely
      rare and only a few case reports have been published. Here we review all of the
      cases of lung cancer from January 2003 to April 2005 in a tertiary teaching
      hospital in Taiwan. A total of six patients (1.77%, 6/339) with primary lung
      cancer demonstrated symptomatic gastro-intestinal metastasis. Three patients had
      squamous cell carcinoma, one had adenocarcinoma, and two had small cell
      carcinoma. Three patients with gastric metastasis were diagnosed via gastro
      endoscopy while one with cecal involvement was diagnosed via colon fiberscopy.
      Two patients with small bowel perforation and intussusception were diagnosed via
      laparotomy. We presented these rare cases and made a review of the literature.

PMID- 17010475
TI  - Actin dynamics at sites of extracellular matrix degradation.
AB  - The degradation of extracellular matrix (ECM) by proteases is crucial in
      physiological and pathological cell invasion alike. In vitro, degradation occurs
      at specific sites where invasive cells make contact with the ECM via specialized
      plasma membrane protrusions termed invadopodia. Here we present an extensive
      morpho-functional analysis of invadopodia actively engaged in ECM degradation and
      show that they are actin comet-based structures, not unlike the well-known
      bacteria-propelling actin tails. The relative mapping of the basic molecular
      components of invadopodia to actin tails is also provided. Finally, a live
      imaging analysis of invadopodia highlights the intrinsic long-term stability of
      the structures coupled to a highly dynamic actin turnover. The results offer new
      insight into the tight coordination between signalling, actin remodelling and
      trafficking activities occurring at sites of focalized ECM degradation by
      invadopodia. In conclusion, invadopodia-associated actin comets are a striking
      example of consistently arising, spontaneous expression of actin-driven
      propulsion events that also represent a valuable experimental paradigm.

PMID- 17010476
TI  - Neuropeptide Y (NPY) modulates oxidative burst and nitric oxide production in
      carrageenan-elicited granulocytes from rat air pouch.
AB  - We studied the effects of neuropeptide Y (NPY) and NPY-related receptor specific
      peptides on functions of carrageenan-elicited granulocytes in vitro and ability
      of NPY to modulate carrageenan-induced air pouch inflammation in rats in vivo.
      Anti-inflammatory effect of NPY comprises reduced granulocyte accumulation into
      the air pouch, to some extent attenuation of phagocytosis, attained via Y1
      receptor, and considerable decrease in peroxide production, albeit mediated via
      Y2 and Y5 receptors activation. Conversely, NPY increases nitric oxide production
      and this potentiation is mediated via Y1 receptor. It is concluded that NPY Y1
      and Y2/Y5 receptors' interaction participates in NPY-induced modulation of
      granulocyte functions related to inflammation.

PMID- 17010477
TI  - Age-related changes in visual acuity, learning and memory in C57BL/6J and DBA/2J
      mice.
AB  - The DBA/2J mouse is a model of age-related pigmentary glaucoma in humans. Visual
      detection, pattern discrimination and visual acuity were evaluated in DBA/2J,
      C57BL/6J, B6.mpc1d (a C57 congenic strain) and D2.mpc1b (a D2 congenic strain)
      mice at 6, 12, 18 and 24 months of age. Mice were also tested in the Morris Water
      Maze and olfactory discrimination learning task. At 6 months, DBA/2J and D2.mpc1b
      mice outperformed C57BL/6J and B6.mpc1d mice in the visual detection task and
      there were no strain differences in performance on the water maze. At 12, 18 and
      24 months, C57BL/6J and B6.mpc1d mice outperformed DBA/2J and D2.mpc1b mice in
      the vision tasks and in the water maze. Strains did not differ in the olfactory
      learning task. Therefore, loss of visual function occurs between 6 and 12 months
      of age in DBA/2J mice. Strain differences in visual task performance accounted
      for a significant proportion of the variance in measures of learning and memory
      in the water maze at 12, 18 and 24 months of age.

PMID- 17010478
TI  - Estrogen receptor alpha and its splice variants in the hippocampus in aging and
      Alzheimer's disease.
AB  - Clinical and experimental studies show that estrogens can have beneficial effects
      on hippocampus-dependent cognitive functions that may be mediated by estrogen
      receptor (ER)alpha. We investigated whether menopause and Alzheimer's disease
      (AD) cause changes in this ER subtype. Immunocytochemical staining of ERalpha,
      aromatase and Golgi complex (GC) was performed on paraffin embedded hippocampal
      tissue from women of the pre-, peri- and postmenopausal age. Canonical ERalpha
      mRNA amplicons, ERalpha splice variants (del.2, del.4, del.7, MB1) and aromatase
      transcripts were measured by Q-PCR in frozen hippocampal samples of AD and
      matched control cases. Nuclear ERalpha, aromatase and the GC enhanced during
      aging in women indicating availability of locally synthesized estrogens that may
      up-regulate ERalpha by which neuronal metabolism can be augmented in the
      hippocampus after the menopause. In AD cases canonical and alternatively spliced
      ERalpha mRNA, and aromatase gene expression were down-regulated suggesting a
      deficit in local estrogen levels and diminished signalling through ERalpha. The
      major ERalpha splice variants in the hippocampus were found to be MB1 and del.4.
      A novel ERalpha isoform TADDI was isolated and sequenced from two female
      patients. It lacks 31 bp at the junction between exons 3 and 4 with an insertion
      of 13 nucleotides from the middle of the exon 2.

PMID- 17010479
TI  - Design, synthesis, biochemical evaluation and antimycobacterial action of
      phosphonate inhibitors of antigen 85C, a crucial enzyme involved in biosynthesis
      of the mycobacterial cell wall.
AB  - Phosphonate inhibitors of antigen 85C were prepared. The inhibitors, comprising a
      phosphonate moiety, mycolic acid mimetic and a trehalose surrogate, contain
      substituted benzyl alcohols, N-(omega-hydroxyalky)phthalimide, 2-phenylethanol or
      4-(phthalimido)butanol as trehalose mimetics, and an alkyl chain of different
      lengths mimicking the mycolic acid side chain. The best compounds inhibited the
      mycolyltransferase activity of antigen 85C with IC(50) in the low micromolar
      range and inhibited the growth of Mycobacterium avium in culture. The best
      compounds in the 3-phenoxybenzyl- and omega-(phthalimido)alkoxy series, ethyl 3
      phenoxybenzyl butylphosphonate (4a) and (1,3-dioxo-1,3-dihydro-2H-isoindol-2
      yl)methyl ethyl heptylphosphonate (5c) displayed IC(50) values of 2.0 and 1.3
      microM, respectively, in a mycolyltransferase inhibition assay. In a M. avium
      growth inhibition assay MIC of 4a and (1,3-dioxo-1,3-dihydro-2H-isoindol-2
      yl)methyl ethyl nonylphosphonate (5d) were 248.8 and 84.5 microg/mL,
      respectively.

PMID- 17010480
TI  - Synthesis and evaluation of a small library of graftable thrombin inhibitors
      derived from (L)-arginine.
AB  - Novel piperazinyl-amide derivatives of N-alpha-(aryl-sulfonyl)-L-arginine were
      synthesized as graftable thrombin inhibitors, in the context of biomaterials'
      design. The possible disturbance of biological activity due to a variable spacer
      arm fixed on the N-4 piperazinyl position and the introduction of a
      trifluoromethyl group as XPS (X-ray Photoelectron Spectroscopy) tag on the
      sulfonamide moiety were evaluated in vitro against human alpha-thrombin. All the
      compounds of the library were found to be active at the micromolar level, as the
      reference TAME (N-tosyl-L-arginine methyl ester). The blood compatibilization
      improvement of poly(ethylene terephthalate) (PET) membrane, coated or grafted by
      wet chemistry treatment with one representative inhibitor of the library, was
      also evaluated, showing interesting decrease in blood clot formation.

PMID- 17010481
TI  - High selective leishmanicidal activity of 3-hydroxy-2-methylene-3-(4
      bromophenyl)propanenitrile and analogous compounds.
AB  - Sixteen not new aromatic compounds were prepared by one-pot reaction i.e. through
      Baylis-Hillman reaction and were the first time evaluated against promastigote
      Leishmania amazonensis and infected mammalian cells. Most of the compounds were
      selectively more active against amastigotes than the reference drug sodium
      stibogluconate (Pentostam, IC(50)=44.7 microM). We found that 3-hydroxy-2
      methylene-3-(4-bromophenyl) propanenitrile (13) was the most active (IC(50)=12.5
      microM) and safer compound (0.0 (0.9); % macrophage LDH release), being the lead
      compound.

PMID- 17010482
TI  - Synthesis and in vitro antitumor effect of diclofenac and fenoprofen thiolated
      and nonthiolated polyaspartamide-drug conjugates.
AB  - This paper reports the synthesis and antiproliferative effects of new thiomer
      diclofenac and fenoprofen conjugates, hydrophilic, bioadhesive, polymeric
      prodrugs, as well as antiproliferative effects of diclofenac, fenoprofen and a
      series of previously described polymer-fenoprofen conjugates on five tumor cell
      lines. Thiolated and nonthiolated polyaspartamides were the chosen polymeric
      components. Drug-loading ranged from 5.6 to 22.4%, and the amount of SH groups
      ranged from 6.9 to 45.6micromol g(-1). Tensile studies demonstrated a clear
      correlation between the amount of thiol and the mucoadhesive properties of the
      conjugates. The growth-inhibitory activity of the tested polymer-drug conjugates
      demonstrates that polyaspartamide-type polymers, especially thiolated polymers,
      enable inhibition of tumor cell growth with significantly lower doses of the
      active substance.

PMID- 17010485
TI  - [Pneumococcal vaccination: expected benefits in adults].
AB  - PURPOSE: Streptococcus pneumoniae is one of the leading causes of bacterial
      pneumonia, meningitis and acute otitis media in children and adults worldwide.
      Polysaccharide pneumococcal vaccines have been available for approximately 50
      years and conjugate vaccines, which generate immunological memory even at an
      early age but have limited serotype coverage, have recently been developed.
      CURRENT KNOWLEDGE AND KEY POINTS: Although the polysaccharide vaccine is
      considered effective in preventing invasive pneumococcal disease (IPD) in adults,
      its efficacy against pneumonia and among older or immunocompromised individuals
      is still controversial. On the other hand, the conjugate vaccine for children
      allows a large reduction in the incidence of IPD and in the rate of pneumococcal
      colonization in the general population through herd immunity, but its serotype
      coverage remains low in adults and serotype replacement may be expected in the
      long-term. FUTURE PROSPECTS: In the present context of widespread antibiotic
      resistance, it is of the utmost importance to assess the expected benefits of
      pneumococcal vaccination, in order to be able to use it optimally in all
      population parts.

PMID- 17010486
TI  - Biomonitoring of airborne mercury with perennial ryegrass cultures.
AB  - A biomonitoring network with grass cultures was established near a chlor-alkali
      plant and the mercury concentration in the cultures were compared with the
      average atmospheric total gaseous mercury (TGM). Biomonitoring techniques based
      on different exposure periods were carried out. When comparing the mercury
      concentration in the grass cultures, both the average atmospheric TGM
      concentration during exposure and the exposure time determined to a large extent
      the accumulation rate of TGM. The maximum tolerable level of mercury in grass
      (approximately equal to 110 microg kg(-1) DM) corresponds with an average TGM
      concentration of 11 ng m(-3) for 28 days exposure. The background concentrations
      in grass were on an average 15 microg kg(-1) DM and the effect detection limit
      (EDL) was 30 microg kg(-1) DM. This value corresponds with an average TGM
      concentration of 3.2 and 4.2 ng m(-3) for 28 and 14 days exposure, respectively,
      which is in turn the biological detection limit (BDL) of ambient TGM. Exposures
      for 7 days were less appropriate for biomonitoring.

PMID- 17010487
TI  - Landscape ecology of the Guanting Reservoir, Beijing, China: multivariate and
      geostatistical analyses of metals in soils.
AB  - Surface soil samples were collected from 52 sites around Guanting Reservoir in
      Beijing, China, and contents of 'total' metals (Cu, Zn, Pb, Cd, As, Ni and Cr)
      were determined. The results indicate that the degree of heavy metal pollution in
      the soils declines in the order of Cd>Cr>Zn>As>Cu>Ni>Pb. Based on the results of
      a combination of multivariate statistics and geostatiscal analyses, it was
      concluded that land application of phosphate fertilizer, wastewater and sludge
      were the primary sources of Cd and Zn in soils. Whereas As, Cu, Cr and Ni in some
      soils were due to natural rock weathering. The sources of Pb in soils only
      partially originated from land application of phosphate fertilizer, but mainly
      from vehicle exhaust. The greatest concentrations of all metals, except for Pb,
      were found in Huailai County and the towns of Yanghedaqiao and Guanting.

PMID- 17010488
TI  - Congener distribution of polybrominated diphenyl ethers in feral carp (Cyprinus
      carpio) from the Llobregat River, Spain.
AB  - Feral carp were collected at two Spanish rivers, Anoia and Cardener, showing PBDE
      levels from 29 to 638 ng/g lipid weight (lw) and from 54 to 744 ng/g lw,
      respectively. Sediments were also collected, showing PBDE contamination between 2
      and 10 ng/g dry weight (dw). Differences in PBDE profiles between sediments and
      fish were noticed. Contribution of BDE-47 in sediment was up to 11%, whereas it
      contributed 37-90% of PBDEs in fish. Similar results were observed for BDE-154,
      which was only detected in one sediment sample, but presented high contribution
      in carp. In contrast, BDE-99 contributed up to 32% in sediments, but it was not
      detected in fish. Similar results were observed for BDE-153, BDE-183 and BDE-209.
      The main reason for their concentration decrease or absence in biota may be due
      to low bioavailability potential or due to biotransformation processes.

PMID- 17010489
TI  - Polybutylcyanoacrylate nanoparticles as a carrier for mitomycin C in rabbits
      bearing VX2-liver tumor.
AB  - Polybutylcyanoacrylate nanoparticles (PBCA-NP) were prepared by addition of the
      monomer to an aqueous phase containing dextran 70 and loaded with mitomycin C
      (MMC-PBCA-NP), a highly effective anticancer drug. When injected into mice, MMC
      PBCA-NP accumulated more in the liver than did free MMC. In contrast, MMC-PBCA-NP
      accumulated less in the heart and kidney than did free MMC. However, when MMC
      PBCA-NP and MMC were administered to rabbits bearing VX2 cells implanted into the
      liver, the antiproliferative effects on the tumor cells of both drugs were
      similar. Histological analyses indicated that organization of myocardial
      filaments was disrupted and vacuolization was observed in the MMC treated group,
      whereas MMC-PBCA-NP treatment did not appear to damage the host's heart. Hydropic
      degeneration of renal tubular epithelia was observed in the MMC treated group and
      not in the control group, whereas MMC-PBCA-NP treatment did not appear to damage
      the host's kidney.

PMID- 17010490
TI  - Illness-related stigma, mood and adjustment to illness in persons with hepatitis
      C.
AB  - We examined stigma in persons with hepatitis C and its relationship with mood and
      adjustment to illness. We studied 87 persons awaiting interferon treatment for
      hepatitis C at St James's Hospital, Dublin. Stigma was assessed using Fife's
      Experience of Illness scale. A structured clinical interview was used to
      establish DSM-IV diagnosis. The Hospital Anxiety and Depression Scale (HADS) and
      Beck Depression Inventory (BDI) were also used as measures of mood. Factor
      analysis and clustering around latent variables analysis were used to assess
      scale structure and reliability. The stigma scale had an overall reliability of
      0.94. A strong dimension of fear of disclosure emerged, from item analysis,
      together with dimensions of social isolation and social rejection. Stigma was
      higher in those in manual occupations and the unemployed than in those in non
      manual occupation. There were high levels in those with disease associated with
      injecting drug use and iatrogenic disease caused by transfusion or anti-D blood
      products, and low levels in those who had been treated for haemophilia with
      contaminated products or whose hepatitis was of unknown origin. Adjusted for
      confounders, a 1-decile increase in stigma score had an odds ratio of 1.4 for DSM
      IV depression and similar associations with depression on the HADS and BDI.
      Stigma was also associated with poorer work and social adjustment, lower
      acceptance of illness, higher subjective levels of symptoms and greater
      subjective impairment of memory and concentration. These associations were
      replicated in the non-depressed subsample. The results underline the strong link
      between stigma and well-being in hepatitis C. However, they also suggest that
      stigma is a complex construct that will require further research to elucidate.

PMID- 17010491
TI  - Rise of testosterone, nortestosterone, and 17beta-estradiol concentrations in
      peripheral blood plasma of pigs after sublingual application in vivo.
AB  - Application of endogenous anabolic steroids to meat producing animals is not
      allowed in the EU. In other countries application is practised due to a low oral
      activity based on an efficient first liver passage. This contrasts with
      pharmacological investigations where steroids were readily absorbed by the buccal
      and sublingual mucosa using absorption enhancers. An in vivo study was performed
      to clarify possible absorption after sublingual applications of one milligram
      portions of either testosterone (T), 17beta-estradiol (E), or nortestosterone
      (NT) in sesame oil to castrated male pigs (n=5) without specific delivery systems
      during anaesthesia. Blood samples were drawn using jugular vein catheters for 15
      min before and 3h after application. Hormone concentrations were determined by
      Radioimmunoassay for T and E or Enzymeimmunoassay for NT. For all steroids a
      slight increase was measurable one minute after application. Maximal values for
      T, E, and NT were 2.5 ng/ml, 1.5 ng/ml and 4.2 ng/ml, respectively, and were
      observed after 10 min. The concentrations of the three steroids decreased slowly
      thereafter but were still significantly elevated 1-3h after application. Oral
      absorption of steroids without enhancers should be considered in risk analysis.

PMID- 17010493
TI  - What is the evidence for paediatric dental sedation?
AB  - BACKGROUND AND RATIONALE: Sedation can be used to relieve anxiety and manage
      behaviour in children, unfortunately it is difficult to determine from published
      research which agents, dosages and techniques are effective. OBJECTIVE: To
      evaluate the relative efficacy of the various conscious sedation techniques and
      dosages for behaviour management in paediatric dentistry. DESIGN AND KEY METHODS:
      Relevant databases and reference lists from articles were searched up to December
      2005. 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. RESULTS: Sixty-five studies were included
      with 3372 subjects in total. Overall quality of studies was found to be
      disappointing with poor reporting often the main problem. CONCLUSIONS: Authors
      were not able to reach any definitive conclusion on which was the most effective
      drug or method of sedation used for anxious children due to issues with the
      quality and validity of published studies to date.

PMID- 17010492
TI  - Testing of antidotes for organophosphorus compounds: experimental procedures and
      clinical reality.
AB  - According to current knowledge, inhibition of acetylcholinesterase (AChE) is a
      very important toxic action of organphosphorus compounds (OP). Hence, it is
      obvious to follow the AChE activity in order to quantify the degree of inhibition
      and to assess possible reactivation. Red blood cell (RBC)-AChE provides an easily
      accessible source to follow the AChE status also in humans. There are many
      reports underlining the appropriateness of RBC-AChE as a surrogate parameter that
      mirrors the synaptic enzyme. With this tool at hand, we can study the kinetic
      parameters of inhibition, spontaneous and oxime-induced reactivation, as well as
      aging with human RBCs under physiological conditions in vitro. Moreover, we can
      simulate the influence of inhibitor and reactivator on enzyme activity and can
      calculate what happens when both components change with time. Finally, we can
      correlate under controlled conditions the AChE-status in intoxicated patients
      with the clinical signs and symptoms and determine the time-dependent changes of
      the oxime and OP concentration. Data of a clinical trial performed in Munich to
      analyze the value of obidoxime has elucidated that obidoxime worked as expected
      from in vitro studies. Following a 250mg bolus, obidoxime was administered by
      continuous infusion at 750mg/24h aimed at maintaining a plasma concentration of
      10-20microM obidoxime. This oxime concentration reactivated RBC-AChE>20% of
      normal in most cases of OP poisoning by diethylphosphoryl compounds within a few
      hours. The degree of reactivation fitted theoretical calculations very well when
      the obidoxime and paraoxon concentrations were fed into the model. Only in a few
      cases reactivation was much lower than expected. The reason for this effect is
      probably based on the polymorphism of paraoxonase (PON1) in that the
      (192)arginine phenotype does hardly hydrolyze the arising diethylphosphoryl
      obidoxime. While this variable may complicate a proper assessment even more, we
      are confident that the in vitro evaluation of all relevant kinetic data enables
      the prediction of probable effectiveness in humans. These studies also help to
      understand therapeutic failures and to define scenarios where oximes are
      virtually ineffective. These include poisonings with rapidly aging phosphylated
      AChE, late start with an effective oxime and too early discontinuation of oximes
      in poisonings with a persistent OP. The experience gathered with the experimental
      and therapeutic approaches to human poisoning by OP pesticides may be helpful
      when oximes have to be selected against nerve agents.

PMID- 17010494
TI  - Acute activation of glucose uptake by glucose deprivation in L929 fibroblast
      cells.
AB  - Glucose is a very important energy source for a wide variety of cells, and the
      ability of cells to respond to changes in glucose availability or other cell
      stresses is of critical importance. Many mammalian cells respond to acute stress
      by increasing the V(max) of transport through GLUT1; the most ubiquitously
      expressed glucose transporter isoform. This study investigated the acute response
      of glucose uptake to glucose deprivation in L929 fibroblast cells--a cell line
      that expresses only the GLUT1 transporter. Results indicated that glucose
      deprivation of only a minute activated glucose uptake 10-fold and reached a
      maximum of 20-fold within 10 min. The activation was dose dependent and only
      partially muted by addition of up to 20mM pyruvate as an alternate energy source.
      In contrast to the kinetics of acute metabolic stress, glucose deprivation
      decreased the K(m) of transport, but did not alter the V(max). Maximal activation
      of glucose transport by glucose deprivation was completely additive to activation
      of transport by methylene blue--a stimulant that increased the V(max) of
      transport without a change in the K(m). Glucose-deprived activation of glucose
      transport was not inhibited by wortmannin or herbimycin A, but was completely
      inhibited by phenylarsine oxide. Altogether, the data indicate that L929
      fibroblast cells respond quickly and robustly to the cell stress of glucose
      deprivation and methylene blue treatment by two distinct activation pathways.

PMID- 17010495
TI  - Molecular characterization of laforin, a dual-specificity protein phosphatase
      implicated in Lafora disease.
AB  - Lafora disease is a progressive myoclonus epilepsy with an early fatal issue. Two
      genes were identified thus far, the mutations of which cause the disease. The
      first one, EPM2A, encodes the consensus sequence of a protein tyrosine
      phosphatase. Its product, laforin, is the object of the present work. We analysed
      in detail the amino acid sequence of this protein. This suggested, as also
      observed by others, that it could present two domains, a carbohydrate-binding
      domain (CBM20, known as a starch-binding domain) and the catalytic domain of a
      dual-specificity protein phosphatase. We produced the enzyme as two different GST
      fused proteins and as an N-terminally His-tagged protein. Differences in
      solubility were observed between the constructs. Moreover, the N-terminal
      carbohydrate-binding domain contains a thrombin cleavage site, which is hidden in
      the simplest GST-fusion protein we produced, but was accessible after introducing
      a five-residue linker between the engineered cleavage site and the enzyme N
      terminus. The two types of constructs hydrolyse pNPP and OMFP with kinetic
      parameters consistent with those of a dual-specificity phosphatase. We show in
      addition that the protein not only binds glycogen, but also starch, amylose and
      cyclodextrin. Neither binding of glycogen nor of beta-cyclodextrin appreciably
      affects the phosphatase activity. These results suggest that the role of the N
      terminal domain is rather that of targeting the protein in the cell, probably to
      glycogen and the protein complexes attached to it, rather than that of directly
      modulating the catalytic activity.

PMID- 17010496
TI  - Natural compounds as a source of protein tyrosine phosphatase inhibitors:
      application to the rational design of small-molecule derivatives.
AB  - Reversible phosphorylation of tyrosine residues is a key regulatory mechanism for
      numerous cellular events. Protein tyrosine kinases and protein tyrosine
      phosphatases (PTPs) have a pivotal role in regulating both normal cell physiology
      and pathophysiology. Accordingly, deregulated activity of both protein tyrosine
      kinases and PTPs is involved in the development of numerous congenitically
      inherited and acquired human diseases, prompting obvious pharmaceutical and
      academic research interest. The development of compound libraries with higher
      selective PTP inhibitory activity has been bolstered by the realization that many
      natural products have such activity and thus are interesting biologically lead
      compounds, which properties are widely exploited. In addition, more rational
      approaches have focused on the incorporation of phosphotyrosine mimetics into
      specific peptide templates (peptidomimetic backbones). Additional factors
      furthering discovery as well as therapeutic application of new bioactive
      molecules are the integration of functional genomics, cell biology, structural
      biology, drug design, molecular screening and chemical diversity. Together, all
      these factors will lead to new avenues to treat clinical disease based on PTP
      inhibition.

PMID- 17010497
TI  - Optimal refresher training intervals for AED and CPR skills: a randomised
      controlled trial.
AB  - AIM: To determine the optimal refresher training interval for lay volunteer
      responders in the English National Defibrillator Programme who had previously
      undertaken a conventional 4-h initial class and a first refresher class at 6
      months. METHODS: Subjects were randomised to receive either two additional
      refresher classes at intervals of 7 and 12 months or one additional refresher
      class after 12 months. RESULTS: Greater skill loss had occurred when the second
      refresher class was undertaken at 12 compared with 7 months. Skill retention
      however, was higher in the former group, ultimately resulting in no significant
      difference in final skill performance. There was no significant difference in
      performance between subjects attending two versus three refresher classes. On
      completion of refresher training all subjects were able to deliver countershocks,
      time to first shock decreased by 17s in both groups, and the proportion of
      subjects able to perform most skills increased. The execution of several
      important interventions remained poor, regardless of the total number of classes
      attended or the interval between them. These included CPR skills, defibrillation
      pad placement, and pre-shock safety checks. Refresher classes held more
      frequently and at shorter intervals increased subjects' self-assessed confidence,
      possibly indicating greater preparedness to use an AED in a real emergency.
      CONCLUSIONS: This study shows that the ability to deliver countershocks is
      maintained whether the second refresher class is held at seven or 12 months after
      the first. To limit skill deterioration between classes, however, refresher
      training intervals should not exceed 7 months. The quality of instruction given
      should be monitored carefully. Learning and teaching strategies require review to
      improve skill acquisition and maintenance.

PMID- 17010498
TI  - Pregnancy-related deaths in four regions of Europe and the United States in 1999
      2000: characterisation of unreported deaths.
AB  - OBJECTIVE: We compared official maternal mortality statistics with those from a
      special study covering all pregnancy-associated deaths in two European countries
      (Finland and France) and in two US states (Massachusetts and North Carolina) in
      1999-2000 to characterize pregnancy-related deaths that are not included in
      official statistics. STUDY DESIGN: We linked the official ICD-10-based maternal
      mortality data for 84 deaths with study data on 404 pregnancy-associated deaths.
      RESULTS: Of the pregnancy-associated deaths, 151 were pregnancy-related. We found
      69 pregnancy-related deaths that had not been included as maternal deaths, and
      two deaths coded as maternal deaths that did not meet our definition for a
      pregnancy-related death. In total, 58 of these 69 deaths were from medical causes
      and 11 were from external causes or injuries (10 postpartum depression-related
      suicides and one accidental drug poisoning). The unreported deaths due to medical
      causes included 27 direct, 15 indirect, and two direct/indirect pregnancy-related
      deaths and 14 possibly pregnancy-related deaths. The most common causes of the
      unreported deaths due to medical causes were intracerebral hemorrhage (7 deaths),
      peripartum cardiomyopathy (4), pulmonary embolism (4) and pregnancy-induced
      hypertension (4). CONCLUSIONS: The collection of data on pregnancy-related and
      pregnancy-associated deaths is useful for countries with low maternal mortality
      figures. The use of various data-collection methods may substantially increase
      the quality of maternal mortality statistics.

PMID- 17010499
TI  - Chronic hypertension is an independent risk factor for preeclampsia and preterm
      delivery in women with rheumatologic diseases: a population-based study.
AB  - OBJECTIVE: The objective was to determine the prevalence of maternal and
      perinatal complications among patients with rheumatologic diseases (RD) and to
      investigate the maternal risk factors for preeclampsia and preterm delivery among
      RD patients. STUDY DESIGN: A retrospective population-based cohort study was
      conducted. The study group comprised women with RD; the control group comprised
      patients without RD. The obstetric and neonatal outcomes of the groups were
      compared, and the data were obtained from a computerized database. RESULTS:
      During the study period, there were 179 deliveries by 125 women with RD. The
      prevalence of severe preeclampsia, chronic hypertension, pregestational diabetes,
      oligohydramnios, preterm deliveries and cesarean sections was significantly
      higher in the RD group than in the control group. Mean birth weight was
      significantly lower in the study group compared with the general population.
      Maternal RD was found to be an independent risk factor for preterm delivery and
      severe preeclampsia (OR 3.59; 95% CI: 2.52-5.11; OR 3.05; 95% CI: 1.44-6.45,
      respectively). The presence of chronic hypertension in patients with RD was found
      to be an independent risk factor for severe preeclampsia and preterm delivery (OR
      12.2; 95% CI: 2.1-69.8; OR 3.8; 95% CI: 1.1-12.7, respectively). CONCLUSION:
      Chronic hypertension is an independent risk factor for preterm delivery and
      severe preeclampsia among RD patients.

PMID- 17010500
TI  - A computerized method for accurately predicting fetal macrosomia up to 11 weeks
      before delivery.
AB  - OBJECTIVE: To improve the prediction of birth weight and fetal macrosomia by
      combining sonographically derived fetal biometric data with routinely recorded
      pregnancy-specific information. STUDY DESIGN: Retrospective data were obtained
      for 218 normal gravidas who had obstetrical ultrasonography performed within 11
      weeks of delivery. Multiple regression was employed to derive a set of equations
      for predicting birth weight that used different combinations of ultrasonographic
      and pregnancy-specific variables. RESULTS: A set of 38 unique combination
      equations was derived to accurately predict birth weight up to 11 weeks before
      delivery. The equations use different combinations of ultrasonographic and
      pregnancy-specific variables, so that predictions are still possible in the face
      of missing data. When ultrasonographic measurements are taken within 3 weeks of
      delivery, fetal macrosomia is predicted with 75% sensitivity, 93% specificity,
      and 67% and 95% positive and negative predictive value, respectively. The
      equations are equally as accurate for primiparous and multiparous women from all
      racial groups. A jackknifing procedure was used to validate the predictive
      accuracy of the equations for use with new subjects. CONCLUSION: The combined
      approach of predicting fetal macrosomia using ultrasonographic fetal measurements
      and pregnancy-specific characteristics is superior to pre-existing approaches
      that rely on either method alone. The method can be used up to 11 weeks before
      delivery, allowing fetal macrosomia to be predicted reliably in low-risk
      populations sufficiently early for prospective clinical intervention to be
      undertaken.

PMID- 17010501
TI  - Factors associated with the length of the latent phase during labor induction.
AB  - OBJECTIVE: To evaluate the factors that are associated with the length of the
      latent phase during labor induction in nulliparous women. STUDY DESIGN: During a
      6-month period, all nulliparous women with a viable fetus of at least 36 weeks
      gestation who underwent induction of labor were identified. Demographic and
      intrapartum data were abstracted from the medical record. In an effort to
      understand the association of different factors with the length of the latent
      phase, both univariable and multivariable analyses were employed. RESULTS: The
      median length of the latent phase for the women available for analysis (N=397)
      was 384 min with an interquartile range of 240-604 min. In univariable analysis,
      a greater maternal age, a medical indication for induction, and unripe cervical
      status at admission (assessed by either modified Bishop score or use of cervical
      ripening agents) were significantly associated with a latent phase of at least 12
      h. In multivariable analysis, the only variables that continued to be
      independently associated with a latent phase of at least 12 h were modified
      Bishop scores of 0-2 (adjusted odds ratio 42.0, 95% confidence interval 9.7,
      183.2) and 3-5 (adjusted odds ratio 9.3, 95% confidence interval 2.1, 40.9).
      CONCLUSION: A woman's modified Bishop score at admission for labor induction, but
      not other risk factors typically associated with cesarean, is associated with
      length of the latent phase.

PMID- 17010502
TI  - Interaction of piroxicam and meloxicam with DMPG/DMPC mixed vesicles: anomalous
      partitioning behavior.
AB  - Small unilamellar vesicles (SUVs) formed from a mixture of
      dimyristoylphosphatidylcholine (zwitterionic lipid with bulkier headgroup) and
      dimyristoylphosphatidylglycerol (anionic lipid with relatively smaller headgroup)
      allows better modulation of the physical properties of lipid bilayers compared to
      SUVs formed by a single type of lipid, providing us with a better model system to
      study the effect of membrane parameters on the partitioning of small molecules.
      Membrane parameter like packing of the vesicles is more pronounced in the gel
      phase and hence the study was carried out in the gel phase. Mixed vesicles formed
      from DMPG and DMPC with the mole percent ratio of 100:0, 90:10 and 80:20 were
      used for this study. As examples of polar solutes, piroxicam and meloxicam, two
      Non Steroidal Anti-inflammatory Drugs (NSAIDs) were chosen. The pH was adjusted
      to 2.8 in order to eliminate the presence of anionic forms of the drugs that
      would not approach the vesicles containing negatively charged DMPG (50%
      deprotonated at pH 2.8). Surface potential measured by using TNS (2,6-p
      toluidinonaphthalene sulfonate, sodium salt) as surface charge sensitive probe
      showed no significant changes in the surface electrostatics in increasing DMPC
      content from 0 to 20%. Transmission electron microscopy (TEM) was used to
      characterize SUVs of different composition at pH 2.8. The average diameter of the
      mixed vesicles was found to be smaller than that formed by DMPG and DMPC alone.
      Partition coefficient (K(P)) of piroxicam and meloxicam was measured using
      intrinsic fluorescence of these molecules. K(P) value of piroxicam decreases with
      increase in DMPC content whereas it increases with DMPC content in case of
      meloxicam. This anomalous behavior of partitioning is unexpected since there was
      no significant change in surface pH of the vesicles and has been explained in
      terms of lipid packing and water penetration in the lipid bilayer.

PMID- 17010503
TI  - Response to environmental flows in the Lower Tarim River, Xinjiang, China: an
      ecological interpretation of water-table dynamics.
AB  - Increased water-dependent development and utilization have led to significant
      environmental and hydrological degradation of the Tarim River in western China
      and its dependent ecosystems. Between the 1950s and 1970s, 350 km of the lower
      reaches were drained and between 1960 and 1980 the water-table fell from between 
      2 and -3 m to between -8 and -10 m. Subsequently, riparian ecosystems were
      seriously degraded. In 2000, the Chinese government launched a program to restore
      the lower reaches of the river. Four environmental flows of 1034 x 10(6) m(3)
      were released from 2000 to 2002. This paper interprets and discusses the
      ecological significance of changes following the releases and identifies the
      relationship between water-table dynamics and vegetation responses. Short-term
      objectives for river restoration are proposed with possible monitoring parameters
      suggested.

PMID- 17010504
TI  - Modeling protected species as an undesirable output: the case of sea turtle
      interactions in Hawaii's longline fishery.
AB  - Interactions with sea turtles have occurred at an alarming rate in swordfish
      longlining in Hawaii in recent years and various regulations have been put
      forward to protect sea turtles. In order to understand the cost of reducing sea
      turtle interactions, methods have been developed to derive the shadow price of
      sea turtle bycatch based on fisher's welfare loss from a specific regulation.
      This paper illustrates an alternative method of calculating temporal and trip
      specific cost of sea turtle bycatch reduction. The advantages of this method lie
      in the computation of shadow price without assuming specific regulation
      implementation and its relatively modest data requirement. A parametric output
      distance function is used to simultaneously model desirable and undesirable
      catches. Using the duality argument, the revenue-related shadow price of sea
      turtle bycatch can be derived from the estimated distance function. Average
      shadow price of sea turtle bycatch for the period 1991-1999 is estimated to be US
      $30873 in 1991 dollars. Average shadow prices of sea turtle bycatch by trip
      characteristics, such as fishing year, trip type and location are also estimated.
      Such information can be useful for policy makers to analyze tradeoffs and make
      appropriate policy decisions.

PMID- 17010505
TI  - Development and external validation of an extended 10-core biopsy nomogram.
AB  - OBJECTIVES: To test the accuracy of a previously externally validated sextant
      biopsy nomogram in referred men exposed to > or =10 or more biopsy cores.
      Moreover, we explored the hypothesis that a more accurate predictive tool could
      be developed. METHODS: Previous nomogram predictors (age, digital rectal
      examination, prostate-specific antigen, and percent free PSA) were used to assess
      the accuracy of our previous nomogram in a cohort consisting of 2900 men referred
      for prostatic evaluation. Moreover, these variables were complemented with
      sampling density (SD) (i.e., ratio of gland volume and the number of planned
      biopsy cores) within multivariable logistic regression models (LRM) predicting
      presence of prostate cancer (pCA) on the initial 10 or more core biopsy. The LRMs
      were used to develop and internally validate (200 bootstrap resamples) a new
      nomogram in 1162 men from Hamburg, Germany. The LRMs' external validity was
      tested in three separate cohorts (Hamburg, n=582; Milan, n=961; Seattle, n=195).
      RESULTS: The contemporary external validation of the previously validated sextant
      nomogram demonstrated 70% accuracy. Internal validation of the new nomogram
      demonstrated 77% accuracy, and external cohorts demonstrated 73-76% accuracy.
      CONCLUSIONS: In the era of extended biopsy schemes, previously developed
      predictive models are less accurate in predicting the probability of pCA on
      initial biopsy. We developed a new tool that allows obtaining more accurate
      predictions. Moreover, before biopsy, it also allows defining the ideal ratio
      between gland volume and the number of planned biopsy cores that would yield the
      ideal biopsy rate.

PMID- 17010506
TI  - Nephron-sparing surgery: current developments and controversies.

PMID- 17010507
TI  - Functional results after the suburethral sling procedure for urinary stress
      incontinence: a prospective randomized multicentre study comparing the retropubic
      and transobturator routes.
AB  - OBJECTIVES: To compare short-term functional outcomes, urodynamic parameters, and
      quality of life of transobturator and retropubic routes in the cure of urinary
      stress incontinence. POPULATION AND METHODS: This prospective, multicentre study
      involved 88 women undergoing suburethral sling procedure for stress urinary
      incontinence (SUI). The retropubic route (RPR) and the transobturator route (TOR)
      were used in 42 and 46 women, respectively. No difference in epidemiologic and
      preoperative urinary functional status (SUI stage, and pollakiuria, nocturia, and
      urgency rates) was found between the groups. Functional results and quality of
      life were evaluated before surgery and at 1, 3, 6, and 12 mo postoperatively.
      Urodynamic examinations were performed before and 3 mo after surgery. RESULTS:
      The mean follow-up was 10 mo. No difference in the rate of de novo urge
      incontinence and immediate and late voiding dysfunction was noted between the
      groups. No difference in the cure rate was observed between the groups (89.3% in
      the RPR group and 88.6% in the TOR group). RPR was associated with a significant
      decrease in maximum urinary flow and an increase in residual urine volume.
      Quality of life was significantly improved after surgery without difference
      between the groups. CONCLUSIONS: Retropubic and transobturator routes for
      treatment of female SUI have similar high cure rates and quality of life
      improvement. Because of advantages in the rate of complications and postoperative
      pain previously demonstrated on the same population, the transobturator route
      appears to be the best option for the treatment of urinary incontinence.

PMID- 17010508
TI  - Utility of fluorescence in situ hybridization as a non-invasive technique in the
      diagnosis of upper urinary tract urothelial carcinoma.
AB  - OBJECTIVES: To assess the clinical utility of a fluorescence in situ
      hybridization (FISH) assay as a non-invasive method for diagnosing and monitoring
      urothelial carcinoma (UC) in the upper urinary tract (UUT). METHODS: Urine
      specimens from 30 consecutive patients with UUT UC and 19 healthy controls were
      analyzed by means of cytology and FISH. For FISH analysis, labelled probes to
      chromosomes 3, 7, 9, and 17 were used to assess chromosomal abnormalities
      indicative of malignancy. Sensitivity and specificity of both techniques were
      determined and compared. The frequency of chromosomal aberrations of malignant
      cells from UUT was also determined. RESULTS: Overall sensitivity for FISH was
      significantly higher than the corresponding value for urine cytology (76.7% vs.
      36%, respectively, p=0.0056). Specificities for FISH and cytology were 94.7% and
      100%, respectively (p=ns). The positive and negative predictive values for FISH
      were 95.8% and 72%, whereas for cytology they were 100% and 54%, respectively. Of
      the genetically altered nuclei counted, 67%, 54%, and 43% presented polysomy in
      chromosomes 3, 7, and 17, respectively, and 21% presented a homozygous deletion
      of chromosome 9. CONCLUSIONS: FISH assay of chromosomes 3, 7, 9, and 17 performed
      on exfoliated cells from voided urine specimens has greater sensitivity than
      cytology for detecting UUT UC whilst maintaining a similar specificity. The non
      invasive nature of this method and its higher sensitivity could contribute to
      improving the current diagnosis of UUT UC.

PMID- 17010509
TI  - Biosorption of benzidine based textile dyes "Direct Blue 1 and Direct Red 128"
      using native and heat-treated biomass of Trametes versicolor.
AB  - The capacities and mechanisms of native and heat-treated white rot fungus
      "Trametes versicolor" biomass in removing of two different benzidine based dyes
      (i.e., Direct Blue 1, DB-1 and Direct Red 128, DR-128) from aqueous solution was
      investigated with different parameters, such as molecular weight of dye,
      adsorbent dosage, pH, temperature and ionic strength. In the batch system, the
      biosorption equilibrium time for both dyes was about 6h. The maximum biosorption
      was observed at pH 6.0 for DB-1 and at pH 3.0 for DR-128 on the native and heat
      treated fungal biomass. The biosorption capacities of the native and heat-treated
      fungal biomass (at 800 mg/L dye concentration) were found to be 101.1 and 152.3
      mg/g for DB-1 and these were 189.7 and 225.4 mg dye/g biomass for DR-128,
      respectively. The Freundlih and Temkin adsorption isotherm models were used for
      the mathematical description of the biosorption equilibrium. The Freundlich and
      Temkin models were able to describe the biosorption equilibrium of DB-l and DR
      128 on the native and heat-treated fungal preparations. The Freundlich model also
      showed that the small molecular weight dye (i.e., DR-128) had a higher affinity
      of adsorption that than of the higher molecular weight dye (i.e., DB-1). The dye
      biosorption on the fungal biomass preparations followed the second order kinetics
      model.

PMID- 17010510
TI  - Diffusion and solubility coefficients determined by permeation and immersion
      experiments for organic solvents in HDPE geomembrane.
AB  - The chemical resistance of eight organic solvents in high density polyethylene
      (HDPE) geomembrane has been investigated using the ASTM F739 permeation method
      and the immersion test at different temperatures. The diffusion of the
      experimental organic solvents in HDPE geomembrane was non-Fickian kinetic, and
      the solubility coefficients can be consistent with the solubility parameter
      theory. The diffusion coefficients and solubility coefficients determined by the
      ASTM F739 method were significantly correlated to the immersion tests (p<0.001).
      The steady state permeation rates also showed a good agreement between ASTM F739
      and immersion experiments (r(2)=0.973, p<0.001). Using a one-dimensional
      diffusion equation based on Fick's second law, the diffusion and solubility
      coefficients obtained by immersion test resulted in over estimates of the ASTM
      F739 permeation results. The modeling results indicated that the diffusion and
      solubility coefficients should be obtained using ASTM F739 method which closely
      simulates the practical application of HDPE as barriers in the field.

PMID- 17010511
TI  - Dielectric and conductivity measurements as proxy method to monitor contamination
      in sandstone.
AB  - The present work investigates whether dielectric spectroscopy can be used to
      detect contamination, which may leach in a natural porous material, due to the
      spreading of contaminants. For this purpose, dielectric and conductivity
      measurements, in the frequency range from 10 mHz to 1 MHz, were carried out in
      sandstone samples, partially filled or saturated with solutions of leachates, at
      different concentrations. The experimental results suggest the dominant role of
      free water to the measured electrical conductivity and dielectric permittivity in
      contaminated samples with high water content. On the other hand, various
      relaxation mechanisms were observed in dried samples at different leachate
      concentrations. Experimental data were fitted using the Havriliak-Negami
      dielectric relaxation function, superimposed with a conductivity term. The
      determined parameters of the fitting function may serve to distinguish between
      different amounts of leachate in sandstone samples.

PMID- 17010512
TI  - Spatial distribution of polycyclic aromatic hydrocarbons in Terminalia catappa L.
      (Combretaceae) bark from a selected heavy road traffic area of Rio de Janeiro
      City, Brazil.
AB  - The levels of 21 polycyclic aromatic hydrocarbons (PAHs) with molecular weights
      between 128 Da (naphthalene) and 300 Da (coronene) were determined in Terminalia
      catappa L. (Combretaceae) bark. Tree bark samples were collected in the campus of
      Oswaldo Cruz Foundation, a green area located in a very intensive traffic area of
      Rio de Janeiro City, Brazil and about 10 km away from the city center. Samples
      were submitted to ultrasonic extraction with dichloromethane and analyzed by high
      resolution gas chromatography-mass spectrometry. Individual PAH levels varied
      from 1.23 to 327 ng/g and phenanthrene, fluoranthene and pyrene predominated in
      all samples. Total PAH levels ranged from 242 to 1640 ng/g with a mean of 628
      ng/g. The levels of total PAHs and of total carcinogenic PAHs showed not a clear
      dependence with tree location and distances to the main routes of that area. No
      correlation was observed also with PAH levels previously found in total suspended
      particulate thus indicating that in this area tree bark PAH levels cannot be used
      to assess their atmospheric levels.

PMID- 17010513
TI  - Determination of kinetic and equilibrium parameters of the batch adsorption of
      Ni(II) from aqueous solutions by Na-mordenite.
AB  - The potential to remove nickel(II) ions from aqueous solutions using Na
      mordenite, a common zeolite mineral, was thoroughly investigated. The effects of
      relevant parameters solution pH, adsorbent dose, ionic strength, and temperature
      on nickel(II) adsorption capacity were examined. The sorption data followed the
      Langmuir, Freundlich, Langmuir-Freundlich and Dubinin-Radushkevich (D-R)
      isotherms. The maximum sorption capacity was found to be 5.324 mg/g at pH 6,
      initial concentration of 40 mg/L and temperature of 20 degrees C. Thermodynamic
      parameters, viz. changes in standard free energy (DeltaG degrees ), enthalpy
      (DeltaH degrees ) and entropy (DeltaS degrees ) have also been evaluated and the
      results show that the sorption process was spontaneous and endothermic in nature.
      Dynamics of the sorption process were studied and the values of rate constant of
      adsorption, rate constant of intraparticle diffusion were calculated. The
      activation energy (E(a)) was found to be 12.465 kJ/mol in the present study,
      indicating a chemical sorption process involving weak interactions between
      sorbent and sorbate. The sorption capacity increased with the increase of
      solution pH and the decrease of ionic strength and adsorbent dose. The nickel(II)
      ions sorption by the Na-mordenite is not completely attributable to ion exchange.
      Compared to the other adsorbents, the nickel(II) ions show a lower affinity
      towards the clay mineral adsorbents.

PMID- 17010514
TI  - Removal of Reactofix golden yellow 3 RFN from aqueous solution using wheat husk-
      An agricultural waste.
AB  - The wheat husk, an agricultural by-product, has been activated and used as an
      adsorbent for the adsorption of Reactofix golden yellow 3 RFN from aqueous
      solution. In this work, adsorption of Reactofix golden yellow 3 RFN on wheat husk
      and charcoal has been studied by using batch studies. The equibrium adsorption
      level was determined to be a function of the solution pH, adsorbent dosage, dye
      concentration and contact time. The equilibrium adsorption capacities of wheat
      husk and charcoal for dye removal were obtained using Freundlich and Langmuir
      isotherms. Thermodynamic parameters such as the free energies, enthalpies and
      entropies of adsorption were also evaluated. Adsorption process is considered
      suitable for removing color, COD from wastewater.

PMID- 17010515
TI  - No evidence of CRHR1 gene involvement in progressive supranuclear palsy.
AB  - Several genes have been located in the chromosomal region 17q21 genetically
      associated with progressive supranuclear palsy (PSP). Corticotropin releasing
      hormone receptor 1 (CRHR1) is a gene included in this region. In order to
      investigate the possible involvement of CRHR1 in PSP pathogenesis, we measured
      the globus pallidus mRNA expression of this gene using real-time PCR in 12 PSP
      comparing with several control groups composed by 10 Alzheimer's disease, 5
      cerebrovascular disease and 6 healthy controls subjects. We furthermore sequenced
      directly the entire coding region of CRHR1 of two histopathologically confirmed
      PSP patients. Expression pattern of CRHR1 in globus pallidus was similar in all
      groups. We did not find any coding non-synonymous mutation in the patients
      analysed. Our results do not support an involvement of CRHR1 gene in PSP
      pathogenesis.

PMID- 17010516
TI  - Neurofibrillary tangle-related synaptic alterations of spinal motor neurons of
      P301L tau transgenic mice.
AB  - We investigated axosomatic synapses of anterior horn cells of transgenic (TG)
      mice expressing mutant P301L human tau and non-transgenic (NTG) mice using
      electron microscopic methods to demonstrate the relationship between
      neurofibrillary tangles (NFTs) and synaptic alterations. Animals aged 3.5-8.5
      months were used because at this age many motor neurons in TG mice have NFTs. We
      measured the perimeter of anterior horn cell perikarya, the number of boutons and
      total length of boutons in contact with the neuronal perikarya from the
      micrographs of NFT and non-NFT-bearing neurons. We also calculated the proportion
      of the perimeter covered by boutons, density of boutons and mean size of boutons.
      The density of synaptic boutons in contact with NFT-bearing neurons was
      significantly decreased compared to non-NFT-bearing neurons. These findings
      suggest that synaptic reduction occurs during neurofibrillary degeneration and is
      probably associated with NFT. In addition, synaptic boutons were detached from
      NFT-bearing neurons with the resulting space occupied by astrocytic processes,
      suggesting that astrocytes may be involved in the observed synaptic alterations.

PMID- 17010517
TI  - Cullin 5 gene expression in the rat cerebral cortex and hippocampus following
      traumatic brain injury (TBI).
AB  - Cullin-5 (Cul-5), a member of the cullin gene family of scaffold proteins of E3
      ubiquitin-ligase complexes, has a role in proteolysis and cell cycle regulation.
      We recently demonstrated that cul-5 mRNA is ubiquitously expressed in the central
      nervous system. The present study used quantitative real time polymerase chain
      reaction and western blotting to measure changes in cul-5 mRNA and Cul-5 protein
      expression, respectively, in the injured CNS in response to traumatic brain
      injury (TBI). cul-5 mRNA levels were significantly decreased in the ipsilateral
      rat cerebral cortex on Days 1 and 7, but not on Day 3 following TBI. In the
      ipsilateral hippocampus, cul-5 mRNA was significantly reduced on Day 1 after TBI.
      Cul-5 protein levels were significantly decreased in the ipsilateral rat cerebral
      cortex on Days 1-7 post-TBI while levels were significantly lower in the
      ipsilateral hippocampus on Days 3-7 post-TBI. Since Cul-5 is ubiquitously
      expressed in eukaryotic cells and is linked to proteasome-mediated protein
      degradation, it may have a role in CNS cell fate determination under conditions
      of traumatic stress.

PMID- 17010518
TI  - Increased leptin and decreased ghrelin level after smoking cessation.
AB  - Smoking cessation is associated with transient increases in body weight. Leptin
      and ghrelin are known to be major mediators of appetite, weight and the reward
      pathway. Therefore, this study assessed the changes in the plasma leptin and
      ghrelin level and their relationship with the body weight and appetite after
      smoking cessation in the Korean population. Eighteen subjects, who had stopped
      smoking for 2 months were enrolled in this study. The body mass index (BMI), body
      fat mass (BFM), waist-hip ratio (WHR), weight and appetite were measured before
      and after smoking cessation. In addition, the plasma leptin and ghrelin levels
      were measured. The BMI, BFM, WHR, weight and appetite were significantly higher
      than baseline in those who had gave up smoking for 2 months (p<0.05). The plasma
      leptin concentration increased and the plasma ghrelin level decreased after
      smoking cessation. The change in the leptin level was positively correlated with
      the change in the body mass index and body fat mass. These results do not support
      the direct mediation of the leptin-ghrelin-neuropeptide Y (NPY) system on weight
      gain after smoking cessation. It appears that weight and appetite is regulated by
      a more complicated mechanism after smoking cessation.

PMID- 17010519
TI  - Reaction time facilitation by acoustic task-irrelevant stimuli is not related to
      startle.
AB  - Previous research has been interpreted to suggest that the startle reflex
      mediates the RT facilitation observed if intense, accessory acoustic stimuli are
      presented coinciding with the onset of a visual imperative stimulus in a
      forewarned simple RT task. The present research replicated this finding as well
      as the facilitation of startle observed during the imperative stimulus. It
      failed, however, to find any relationship between the size of the blink startle
      reflex elicited by the accessory acoustic stimuli, which differed in intensity
      and rise time, and RT or RT facilitation observed on trials with accessory
      acoustic stimuli. This finding suggests that the RT facilitation is not mediated
      by the startle reflex elicited by the accessory acoustic stimuli.

PMID- 17010520
TI  - Temporal order judgments for audiovisual targets embedded in unimodal and bimodal
      distractor streams.
AB  - We investigated whether the presence of unimodal or bimodal (synchronous)
      distractors would affect temporal order judgments (TOJs) for pairs of
      asynchronous audiovisual target stimuli. Participants made unspeeded TOJs
      regarding which of a pair of auditory and visual stimuli, presented at different
      stimulus onset asynchronies using the method of constant stimuli, occurred first.
      These asynchronous target stimuli were presented in a fixed position amongst a
      stream of three (auditory, visual, or audiovisual) distractors in each block of
      trials. The largest just noticeable differences (JNDs) were reported when the
      target stimuli were presented in the middle (position 3) of the distractor
      stream. Importantly, audiovisual distractors were shown to interfere with TOJ
      performance far more than unimodal (auditory or visual) distractors. The point of
      subjective simultaneity (PSS) was also influenced by the modality of the
      distractors, and by the position of the target within the distractor stream.
      These results confirm the existence of a specifically bimodal crowding effect,
      with audiovisual TOJs being impaired far more by the presence of audiovisual
      distractors that by unimodal auditory or visual distractors.

PMID- 17010521
TI  - Seroepidemiology of Neospora caninum and Toxoplasma gondii in cattle and water
      buffaloes (Bubalus bubalis) in the People's Republic of China.
AB  - A seroepidemiological survey of Neospora caninum and Toxoplasma gondii in cattle
      and water buffaloes was carried out in the People's Republic of China. Serum
      samples were obtained from dairy (n=262, 9 herds in 9 provinces) and beef cattle
      (n=10, 1 herd) and water buffaloes (n=40) in China. All sera were tested for
      antibodies to N. caninum and T. gondii by an enzyme-linked immunosorbent assay
      (ELISA) and an indirect agglutination test (IAT), respectively. The overall
      seroprevalence of N. caninum in dairy cattle was 17.2% (45/262), and the herds
      seroprevalence of N. caninum was 88.9% (8/9), and antibodies to T. gondii were
      present in 6 cows (2.3%). None of the cows had antibodies against both T. gondii
      and N. caninum. Antibodies to T. gondii or N. caninum were not found in beef
      cattle or water buffaloes. The seroprevalence of N. caninum in aborting cows
      (20.2%) was higher than that in non-aborting cows (16.6%) with an odds ratio of
      1.26 (95% CI, 0.54-2.95), but the difference was not statistically significant
      (P>0.05). There was no apparent association of N. caninum seropositivity with age
      or number of pregnancies. This is the first report on the seroprevalence of N.
      caninum in cattle and water buffaloes in China.

PMID- 17010522
TI  - Double roles of hydroxycinnamic acid derivatives in protection against lysozyme
      oxidation.
AB  - Oxidative damage to protein has been implicated in a number of diseases. Much
      interest has been focused on preventing oxidative damage to protein. Here we
      showed that hydroxycinnamic acid derivatives (HCA) were able to inhibit the cross
      linking of protein induced by riboflavin-mediated photooxidation. HCA were also
      found to strongly protect lysozyme from gamma rays irradiation. The antioxidative
      properties of HCA were further studied by laser flash photolysis. Mechanism of
      antioxidant activities of HCA on lysozyme oxidation was discussed. HCA were found
      to protect protein against oxidation by scavenging oxidizing species and
      repairing the damaged protein.

PMID- 17010523
TI  - Expression and genomic profiling of colorectal cancer.
AB  - Colorectal cancer still represents a paradigm for the elucidation of the
      cellular, genetic and molecular mechanisms that underly solid tumor initiation,
      progression to malignancy, and metastasis to distal organ sites. The relative
      ease with which pathological specimens can be obtained by either surgery or
      endoscopy from different stages of tumor progression has facilitated the
      application of omics technologies to allow the genome-wide analysis both at the
      RNA (gene expression) and DNA (aneuploidy) levels. Here, we have reviewed the
      multiplicity of studies appeared to date in the scientific literature on the
      expression and genomic analysis of colorectal cancer, and attempted an
      integration of the profiling data generated and made available in the public
      domain. This approach is likely to pinpoint specific chromosomal loci and the
      corresponding genes which (i) play rate-limiting roles in colorectal cancer, (ii)
      represent putative diagnostic and prognostic markers for the accurate prediction
      of clinical outcome and response to treatment, and (iii) encompass potential
      therapeutic targets. Moreover, cross-species data mining and integration of the
      human colorectal cancer profiles with those obtained from mouse models of
      intestinal tumorigenesis will even more contribute to the elucidation of highly
      conserved pathways and cellular functions underlying malignancy in the GI tract.
      Notwithstanding the above promises, tumor heterogeneity, limited cohort sizes,
      and methodological differences among experimental and bioinformatic approaches
      still poses main obstacles towards the optimal utilization and integration of
      omics profiles.

PMID- 17010524
TI  - The LKB1 tumor suppressor kinase in human disease.
AB  - Inactivating germline mutations in the LKB1 gene underlie Peutz-Jeghers syndrome
      characterized by hamartomatous polyps and an elevated risk for cancer. Recent
      studies suggest the involvement of LKB1 also in more common human disorders
      including diabetes and in a significant fraction of lung adenocarcinomas. These
      observations have increased the interest towards signaling pathways of this tumor
      suppressor kinase. The recent breakthroughs in understanding the molecular
      functions of the LKB1 indicate its contribution as a regulator of cell polarity,
      energy metabolism and cell proliferation. Here we review how the substrates and
      cellular functions of LKB1 may be linked to Peutz-Jeghers syndrome and other
      diseases, and discuss how some of the molecular changes associated with altered
      LKB1 signaling might be used in therapeutic approaches.

PMID- 17010525
TI  - Temporary henna tattooing in siblings--an unusual chemical burn.

PMID- 17010528
TI  - Auditory processing deficits in growth restricted fetuses affect later language
      development.
AB  - An increased risk for language deficits in infants born growth restricted has
      been reported in follow-up studies for more than 20 years, suggesting a relation
      between fetal auditory system development and later language learning. Work with
      animal models indicate that there are at least two ways in which growth
      restriction could affect the development of auditory perception in human fetuses:
      a delay in myelination or conduction and an increase in sensorineural threshold.
      Systematic study of auditory function in growth restricted human fetuses has not
      been reported. However, results of studies employing low-risk fetuses delivering
      as healthy full-term infants demonstrate that, by late gestation, the fetus can
      hear, sound properties modulate behavior, and sensory information is available
      from both inside (e.g., maternal vascular) and outside (e.g., noise, voices,
      music) of the maternal body. These data provide substantive evidence that the
      auditory system is functioning and that environmental sounds are available for
      shaping neural networks and laying the foundation for language acquisition before
      birth. We hypothesize that fetal growth restriction affects auditory system
      development, resulting in atypical auditory information processing in growth
      restricted fetuses compared to healthy, appropriately-grown-for-gestational-age
      fetuses. Speech perception that lays the foundation for later language competence
      will differ in growth restricted compared to normally grown fetuses and be
      associated with later language abilities.

PMID- 17010527
TI  - Anxiety modulation by the heart? Aerobic exercise and atrial natriuretic peptide.
AB  - Exercise has an anxiolytic activity and it increases the concentrations of atrial
      natriuretic peptide (ANP). Because ANP has an anxiolytic activity, this hormone
      might contribute to the anxiolytic effects of aerobic exercise. Cholecystokinin
      tetrapeptide (CCK-4)-induced panic attacks were studied in 10 healthy subjects
      after "quiet rest" or 30 min of aerobic exercise. Plasma ANP concentrations were
      measured before and after exercise or quiet rest using a commercial IRMA kit.
      Compared to quiet rest, CCK-4-induced anxiety was reduced and plasma ANP
      concentrations were increased by prior exercise. This anxiolytic activity of
      exercise was correlated with the increase in plasma ANP concentrations. Our
      results suggest that besides other mechanisms, ANP might be a physiologically
      relevant humoral link between the heart and anxiety-related behavior contributing
      to the acute anxiolytic effects of exercise.

PMID- 17010526
TI  - Abundance and ultrastructural diversity of neuronal gap junctions in the OFF and
      ON sublaminae of the inner plexiform layer of rat and mouse retina.
AB  - Neuronal gap junctions are abundant in both outer and inner plexiform layers of
      the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally
      identified gap junctions were reported primarily in the functionally-defined and
      anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We
      used freeze-fracture replica immunogold labeling and confocal microscopy to
      quantitatively analyze the morphologies and distributions of neuronal gap
      junctions in the IPL of adult rat and mouse retina. Under "baseline" conditions
      (photopic illumination/general anesthesia), 649 neuronal gap junctions immunogold
      labeled for connexin36 were identified in rat IPL, of which 375 were photomapped
      to OFF vs. ON sublaminae. In contrast to previous reports, the volume-density of
      gap junctions was equally abundant in both sublaminae. Five distinctive
      morphologies of gap junctions were identified: conventional crystalline and non
      crystalline "plaques" (71% and 3%), plus unusual "string" (14%), "ribbon" (7%)
      and "reticular" (2%) forms. Plaque and reticular gap junctions were distributed
      throughout the IPL. However, string and ribbon gap junctions were restricted to
      the OFF sublamina, where they represented 48% of gap junctions in that layer. In
      string and ribbon junctions, curvilinear strands of connexons were dispersed over
      5 to 20 times the area of conventional plaques having equal numbers of connexons.
      To define morphologies of gap junctions under different light-adaptation
      conditions, we examined an additional 1150 gap junctions from rats and mice
      prepared after 30 min of photopic, mesopic and scotopic illumination, with and
      without general anesthesia. Under these conditions, string and ribbon gap
      junctions remained abundant in the OFF sublamina and absent in the ON sublamina.
      Abundant gap junctions in the OFF sublamina of these two rodents with rod
      dominant retinas revealed previously-undescribed but extensive pathways for inter
      neuronal communication; and the wide dispersion of connexons in string and ribbon
      gap junctions suggests unique structural features of gap junctional coupling in
      the OFF vs. ON sublamina.

PMID- 17010529
TI  - Exercise and the inflammatory response in chronic obstructive pulmonary disease
      (COPD)--Does training confer anti-inflammatory properties in COPD?
AB  - There is increasing evidence that systemic inflammation plays an important role
      in the pathogenesis of COPD. Inflammatory markers show relationships with
      exercise performance, health related quality of life and breathlessness. These
      are important clinical outcomes in the management of COPD. Even more so is the
      consideration that systemic inflammation in COPD may be directly associated with
      mortality and deterioration of disease. Long-term exercise training clearly has
      beneficial properties in healthy subjects, whether the same is true in COPD
      remains to be seen. This review discusses aspects of the anti-inflammatory
      effects of exercise in relation to patients with COPD. There is intriguing
      evidence that the exercise-induced cytokine response differs in COPD patients
      compared with healthy subjects. We consider the role of IL-6 in the manifestation
      of fatigue in COPD and consider the implications of raised CRP- and TNF-alpha.
      Early data suggests beneficial effects of polyunsaturated fatty acid PUFA
      supplementation and exercise training in combination with appropriate nutritional
      support may yield rewarding therapeutic benefits. This review raises the
      hypothesis that physical training in COPD is associated with immunological
      changes that may confer anti-inflammatory benefits and in part, explain changes
      seen after pulmonary rehabilitation in COPD patients.

PMID- 17010530
TI  - Botulinum Toxin as a novel addition to the antidupuytren armamentarium.

PMID- 17010531
TI  - Medical papyri describe the effects of the Santorini eruption on human health,
      and date the eruption to August 1603-March 1601 BC.
AB  - Egyptian medical papyri date the Santorini eruption, and reconcile the hitherto
      perceived dichotomy between archaeological/historical and scientific data. The
      medical documentation describes ailments, which can only have arisen from a
      volcanic source: ash fallout, rain acidified by ash, and a plume. Furthermore,
      the Egypt described by the medical texts matches the one in the series of so
      called biblical plagues. This match in turn provides the length of time, 19
      months, between the initial and final phases of the eruption, each phase
      contributing to the otherwise odd accumulation of sulfates spread over two
      consecutive biennia (1603-1600 BC) in Greenland's ice core. As a result, the
      initial phase of the eruption can be dated to August 21, 1603 BC, and the final
      one to March 1601 BC, in full agreement with the radiocarbon data (1627-1600 BC)
      based on the outermost ring on the branch of an olive tree killed by the
      eruption.

PMID- 17010532
TI  - Potential roles of allograft inflammatory factor-1 in the pathogenesis of
      hemangiomas.
AB  - Hemangiomas are benign tumors of the vascular endothelium and are the most common
      tumors of infancy. These tumors are characterized by an initial phase of rapid
      proliferation in the first months of life, which is followed, in most cases, by
      spontaneous slow involution. Despite their high prevalence, their detailed
      pathogenesis remains unknown. Recent studies suggest that immunity responses,
      inflammatory cells and their precursors, myeloid cells, play important roles in
      the growth and involution of hemangiomas. The allograft inflammatory factor-1 is
      a powerful gene that is involved in several kinds of inflammatory response
      related diseases. Studies also show that it is implicated in angiogenesis,
      proliferation and differentiation of stem cells, and development of tumors. Taken
      all these evidences into consideration, we hypothesize that allograft
      inflammatory factor-1 plays potential roles in pathogenesis, proliferation and
      involution of hemangioma. Investigating the role of allograft inflammatory factor
      1 in the proliferation and involution of hemangioma will lead to a better
      understanding of pathogenesis of this lesion. Furthermore, the subtle regulation
      of allograft inflammatory factor-1 in the involution of hemangiomas will help
      design a new anti-angiogenic therapy for some tumors.

PMID- 17010533
TI  - Expression of aromatase and 5-alpha-reductase genes in endometrial
      adenocarcinoma.
AB  - The aim of this study was to investigate the expression of genes coding aromatase
      and 5-alpha-reductase type 1 and type 2 in endometrial adenocarcinoma, with
      parallel analysis of testosterone concentrations in serum isolated from blood of
      basilic and ovarian vein. A significant difference between the copy numbers of
      mRNA for 5-alpha-reductase type 1 and type 2 was disclosed. The content of the
      mRNA copies was higher for 5-alpha-reductase type 2 than for type 1. We noted a
      positive correlation between the mRNA copy number for aromatase and 5-alpha
      reductase type 1 as well as between the mRNA copy number for aromatase and 5
      alpha-reductase type 2. A positive correlation was disclosed between the mRNA
      copy number for 5-alpha-reductase type 1 and type 2. We concluded that in tissues
      of endometrial adenocarcinoma, there is expression of aromatase and 5-alpha
      reductase type 1 and 2 genes, and that the expression of aromatase and 5-alpha
      reductase genes in tissues of endometrial adenocarcinoma is not controlled by
      testosterone.

PMID- 17010534
TI  - [Identification of adenoviruses serotypes implicated in haemorrhagic
      conjunctivitis in Tunisia].
AB  - Human adenoviruses (ADV) are distributed worldwide; they are associated with a
      variety of diseases. Some ADV can be implicated in large epidemics of
      conjunctivitis, gastroenteritis and respiratory infections. Classical diagnosis
      of ADV infections is based on virus isolation on cell culture and identification
      of the serotype by neutralization test or hemagglutination inhibition assay.
      However, these methods have a lack of rapidity that makes them impractical in
      clinical situations. With the advent of PCR, the diagnosis of ADV was improved.
      In this work, we have used molecular techniques for the identification of ADV
      serotypes implicated in conjunctivitis in Tunisia. A total of 199 conjunctival
      swabs received between October 2000 and May 2005 were investigated. Serotype
      identification was performed using a PCR followed by restriction enzyme analysis
      in the hexon gene. Typing by sequencing of the PCR product was used to confirm
      the serotype identification. Among the 199 tested clinical specimens, 24% were
      positive for ADV. Two different profiles were observed: one predominant
      corresponding to the majority of the detected ADV; this profile is in favour of
      two distinct serotypes, ADV37 or ADV8; the second profile was specific of ADV4
      and was found in one case observed in 2005. Sequencing confirmed two serotypes:
      ADV8 with an endemoepidemically circulation in our country and ADV4 that appeared
      sporadic. The present work showed the importance of molecular techniques not only
      for ADV detection but also for identification of the circulating serotypes. These
      techniques are practical and interesting mainly for the rapid virological
      investigation during epidemics.

PMID- 17010535
TI  - Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in
      human brain and intestine.
AB  - The serotonin receptor type 3 is a pentameric ligand-gated ion channel regulating
      intestinal motility, nausea, and vomiting in humans. The HTR3B gene codes for the
      subunit B of this receptor. The HTR3B transcription start site is not
      unequivocally identified. In the present study we used transcription start site
      analyses, transcript-specific RT-PCR, and functional promoter analyses to
      identify the 5' structure of the HTR3B gene. According to these experiments, two
      alternative promoters control the expression of different HTR3B transcripts in
      the peripheral and central nervous system. The transcription start sites observed
      in the intestine corresponded to the current human genome annotation (NCBI Build
      36.1, March 2006). The transcription start sites in the brain, however, were
      localized in a region about 4000 bp downstream. The brain transcripts lacked the
      coding first exon of the HTR3B structure published earlier but had an upstream
      extended exon 2 containing a new potential translational start site. Reporter
      gene analyses showed significant promoter activity of the genomic region located
      1560 bp upstream to 93 bp downstream of the brain-specific transcription start
      sites. This data suggests a different transcriptional regulation of the HTR3B
      gene in the peripheral and the central nervous system that leads to the
      expression of transcripts with variations in the 5' coding sequence. Further
      studies on the expression, structure and function of therefore expected tissue
      specific 5-HT(3B) isoforms are required.

PMID- 17010536
TI  - Macrophage MHC receptor 2: a novel receptor on allograft (H-2D(d)K(d))-induced
      macrophage (H-2D(b)K(b)) recognizing an MHC class I molecule, H-2K(d), in mice.
AB  - We previously reported that a population of allograft (H-2D(d)K(d))-induced
      macrophages (AIM) in C57BL/6 (H-2D(b)K(b)) mice exhibited major
      histocompatibility complex (MHC) haplotype (H-2D(d)) specific killing of the
      allograft (e.g., BALB/c skin and Meth A cells; H-2D(d)K(d)) in a macrophage MHC
      receptor (MMR)-dependent manner. In the present study, we isolated a cDNA clone
      encoding a novel receptor (MMR2) on AIM recognizing another MHC class I molecule,
      H-2K(d), by the expression cloning method using H-2K(d) tetramer and a monoclonal
      antibody (mAb; R12) specific for AIM. The cDNA (2359-bp) encoded a 677-amino acid
      polypeptide of a calculated molecular mass of 87 kDa and was found to be
      expressed exclusively on AIM among cells infiltrating into allografts on days 0-9
      after transplantation. Confocal microscopy showed that HEK293T cells transfected
      with this cDNA were reactive toward the H-2K(d) molecule but not toward other MHC
      class I molecules such as H-2D(d), H-2D(b), H-2D(k), H-2K(b), H-2K(k), and H
      2L(d) molecules. The binding of the H-2K(d) molecule to the transfectants was
      inhibited by the addition of R12 or anti-H-2K(d), but not by R15 (a mAb specific
      for H-2D(d) receptor) or anti-H-2D(d), mAb. Flow cytometric analysis revealed
      specific binding of H-2K(d) molecules to AIM (K(d)=2.7x10(-9) M); and the binding
      was completely suppressed by the addition of R12 mAb. These results demonstrate
      that a novel receptor (MMR2) for H-2K(d) molecules was induced on effector
      macrophages responsible for allograft (H-2D(d)K(d)) rejection by H-2D(b)K(b)
      mice.

PMID- 17010537
TI  - Identification of a unique Alu-based polymorphism and its use in human population
      studies.
AB  - Alu elements represent a family of short interspersed DNA elements (SINEs) found
      in primate genomes. These are members of a group of transposable elements that
      integrate into the genome by the process of retrotransposition. Recent
      integrations of Alu elements within the human genome have generated
      presence/absence variants useful as DNA markers in human population studies as
      well as in forensic and paternity analyses. Besides the ease of use, this type of
      marker is unique because the absence of the Alu represents the ancestral form. We
      have identified an Alu-based polymorphism that consists of four alleles in which
      we can predict the evolutionary order. Additionally, we have developed a simple
      PCR plus restriction endonuclease assay to readily distinguish the four alleles.
      We have thus far analyzed DNA from a small set of samples comprising ten
      different ethnic groups. The three populations of African descent exhibited a
      relatively low frequency of the absence allele in contrast to the other
      populations, as well as being the only populations in which all four alleles were
      identified. One presence allele was not found in both European Caucasian and
      South American populations that were sampled, whereas a different presence allele
      was not observed among the sampled Asian populations. Additionally, the four
      allele system identified variations among populations not observed by simply
      scoring as presence/absence variants. Therefore, extending beyond the two-allele
      dimorphic Alu system further elucidates population variations. These features
      afford this marker as a unique tool in the study of both global and regional
      analyses of human populations.

PMID- 17010538
TI  - Helenalin reduces Staphylococcus aureus infection in vitro and in vivo.
AB  - Staphylococcus (S.) aureus is a major udder pathogen causing bovine mastitis.
      Some pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF
      alpha), enhance extracellular and intracellular growth of S. aureus, indicating
      that the inflammatory process favors S. aureus infection. Helenalin is a
      sesquiterpene lactone with potent anti-inflammatory properties. This study was
      designed to evaluate the effects of helenalin on S. aureus infection. First, in
      vitro experiments were conducted. These studies revealed that proliferation of S.
      aureus in bovine mammary epithelial MAC-T cells treated in the presence or
      absence of TNF-alpha was markedly reduced in the presence of helenalin. Secondly,
      in vivo effects of helenalin were investigated. Lactating mice treated in the
      presence or absence of helenalin were challenged by the intramammary route with
      S. aureus and the bacteria in the mammary glands were counted 12 h after
      infection. Significantly less numbers of bacteria were recovered from the
      infected glands of helenalin-treated mice compared with untreated mice. Moreover,
      histological examination of mammary tissue from helenalin-treated mice that were
      challenged with S. aureus indicated that helenalin is able to significantly
      reduce leukocyte infiltration in the mammary gland following S. aureus
      inoculation. Our results show that helenalin reduces S. aureus intracellular
      growth and experimental S. aureus infection. We conclude that helenalin may be of
      potential interest in the treatment of S. aureus-induced mastitis in the bovine
      species.

PMID- 17010539
TI  - Formation of estrogenic products from benzophenone after exposure to sunlight.
AB  - Benzophenone (BP) is a suspected endocrine disrupter that is found in our
      environment. BP undergoes metabolic and photochemical activation. In this study,
      photoproducts of BP were identified using high-performance liquid chromatography
      and mass spectrometry and their estrogenic activity was determined using both in
      vitro and in vivo assays. Although BP showed no estrogenic activity, two
      estrogenic photoproducts were detected after irradiating an aqueous solution of
      BP with UV or sunlight. These active products were identified as 3-hydroxy BP (BP
      3OH) and 4-hydroxyBP (BP-4OH). The formation of hydrogen peroxide H2O2) was
      detected with increasing levels of UV, and the addition of H2O2 to the BP
      solution increased BP-3OH and BP-4OH production under UV irradiation. BP
      hydroxylation was also observed in the reaction with the Fenton reagent
      generating hydroxyl radical without UV irradiation. These results suggest the
      involvement of photochemically generated H2O2 and hydroxyl radical in the BP
      hydroxylation. BP-4OH was more potent than BP-3OH for promoting estrogen receptor
      (ER)-mediated transcription and uterotrophic activity, although both of them
      showed same affinity in ER binding. In conclusion, BP can be converted into ring
      hydroxylated derivatives that have estrogenic activity after exposure to light.

PMID- 17010540
TI  - Nuclear estrogen and progesterone receptors in the oviduct of heifers under
      natural and superovulated estrous cycles.
AB  - Oviducts from 22 crossbred heifers were examined for the presence of nuclear
      estrogen (ERalpha) and progesterone (PR) receptors at different phases (estrus,
      metaestrus and diestrus) of naturally occurring estrous cycles and estrous cycles
      during which superovulation was induced. Receptors were detected by
      immunohistochemistry in the epithelial cells, connective tissue and muscular
      layer of oviductal infundibulum, ampulla, ampullary/isthmic transition and
      isthmus. Epithelial ERalpha was found along the entire oviduct regardless of the
      cycle phase and of the circulating concentrations of 17beta-estradiol (E(2)) and
      progesterone (P(4)). Epithelial PR was found mainly at the ampullary-isthmic
      transition and isthmus and more intensely at the estrus phase but their amount
      was not correlated with P(4) concentrations. ERalpha in the connective tissue was
      more abundant at the infundibulum and ampulla, regardless of the phase of the
      estrous cycle and of E(2) and P(4) circulating concentrations. PR in the
      connective tissue was found mostly at the ampulla, regardless of the estrous
      cycle phase but no correlations were found between amount and P(4)
      concentrations. ERalpha staining intensity in the muscular layer was similar at
      all phases of the estrous cycle and at all anatomical segments of the oviducts.
      However, PR staining was more intense at the isthmus during the metaestrus phase
      and it was negatively correlated with P(4) concentrations. In general, data from
      the present research suggest that P(4) exerts an inhibitory role upon ERalpha and
      PR. Also, no differences were found between animals subjected or not to
      superovulation.

PMID- 17010541
TI  - Peripheral quantitative computed tomography (pQCT) is useful for monitoring bone
      mineral density of the patients who receive hormone replacement therapy.
AB  - OBJECTIVE: A forearm fracture (Colles' fracture) is often the first sign of
      osteoporosis and should alert the patient and physician to the possibility of
      underlying skeletal fragility. Therefore, the establishment of a more accurate
      and reliable method for the measurement of bone mineral density (BMD) at the
      distal radius would be beneficial for the patients who suffer from osteoporosis.
      The objective of the present study was to evaluate the usefulness of peripheral
      quantitative computed tomography (pQCT) to assess the change of BMD at the distal
      radius in early postmenopausal women who receive hormone replacement therapy
      (HRT). METHODS: Twenty healthy early postmenopausal women who were diagnosed as
      osteoporosis or osteopenia were randomized to either HRT or placebo treatment. We
      analyzed BMD of the distal radius by pQCT, lumbar spine by dual-energy X-ray
      absorptiometry (DXA) and the biochemical markers of bone turn over (osteocalcin,
      deoxypyridinoline) every 6 months. RESULTS: The placebo group showed a
      significant decrease from the baseline in the trabecular BMD of the radius at 12
      months (7.4+/-2.5%) (p<0.05), whereas the HRT group showed a slight increase
      (0.7+/-2.2%). The changes in the trabecular BMD of the radius between the HRT and
      placebo groups were statistically different at 12 months (p<0.05). On the other
      hand, in the cortical BMD of the radius, no significant differences were seen
      between the changes of bone densities in the HRT and control groups after 1 year
      of treatment. pQCT could detect a significant loss of BMD of the radius in early
      postmenopausal women after 1 year and HRT prevented its loss. CONCLUSION: Our
      preliminary clinical trial showed that pQCT might be useful for the early
      detection of bone loss in early postmenopausal women and for the monitoring BMD
      of the patients who receive HRT.

PMID- 17010542
TI  - Vitamin K intake and calcifications in breast arteries.
AB  - OBJECTIVES: Vitamin K is an important co-factor in the production of proteins
      that inhibit vascular calcification. A low dietary Vitamin K intake has been
      associated with aortic and coronary calcifications and an elevated cardiovascular
      risk. Calcifications in the arteries of the breasts have also been associated
      with cardiovascular risk, but whether there is a relation with a low Vitamin K
      intake has not yet been studied. METHODS: We conducted a cross-sectional study
      among 1689 women, aged 49-70 years. Dietary Vitamins K1 and K2 intake was
      calculated from a validated food frequency questionnaire. Breast arterial
      calcifications (BAC) were assessed on standard screening mammograms by two
      independent radiologists. With a general linear model mean Vitamins K1, K2 and
      Vitamin K2 subtypes were calculated for women with BAC and without, adjusted for
      age, smoking, diabetes, intake of saturated fat, mono-unsaturated fat, poly
      unsaturated fat and protein- and calcium-intake. RESULTS: BAC was less common in
      the highest (9%) quartile of Vitamin K2 intake, compared to the lowest (13%) (OR
      0.7, 95% CI 0.5-1.1) and not different across quartiles of Vitamin K1 intake.
      Mean Vitamin K2 levels and mean levels of Vitamin K2 subtypes MK-5 through MK-10
      were lower in the participants with BAC (p=0.01) compared to participants without
      BAC. However, after adjustment for aging, smoking, diabetes and dietary factors
      the association of mean Vitamin K2 intake with BAC was no longer significant.
      CONCLUSION: Calcifications in breast arteries are not associated with a lower
      dietary intake of Vitamin K.

PMID- 17010543
TI  - Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for
      cefpodoxime proxetil.
AB  - Self-nanoemulsifying drug delivery systems (SNEDDS) were developed with the
      objective to overcome problems associated with the delivery of cefpodoxime
      proxetil (CFP), a poorly bioavailable high dose antibiotic having pH dependant
      solubility. Solubility of CFP in oily phases and surfactants was determined to
      identify components of SNEDDS. Various surfactants and co-surfactants were
      screened for their ability to emulsify selected oily phases. Ternary phase
      diagrams were constructed to identify area of nanoemulsification for the selected
      systems. The influence of CFP and the pH of dilution medium on the phase behavior
      of selected system were assessed. The globule size of optimized CFP SNEDDS in
      various dissolution media was determined to check the effect of pH on its
      behavior. The optimized CFP SNEDDS needed surfactant content less than 40% and
      yielded nanoemulsion of mean globule size 170 nm, which was not affected by the
      pH of dilution medium. The optimized SNEDDS released CFP completely within 20 min
      irrespective of the pH of dissolution medium.

PMID- 17010544
TI  - Preparation of monolithic matrices for oral drug delivery using a supercritical
      fluid assisted hot melt extrusion process.
AB  - The use of supercritical fluids as plasticisers in polymer processing has been
      well documented. The body of work described in this research paper outlines the
      use of a supercritical CO(2) assisted extrusion process in the preparation of a
      hot melt extruded monolithic polymer matrix for oral drug delivery. Several
      batches of matrix material were prepared with Carvedilol used as the active
      pharmaceutical ingredient (API). These batches were subsequently extruded both
      with and without supercritical CO(2) incorporation. The resultant matrices were
      characterised using steady-state parallel plate rheometry, differential scanning
      calorimetry (DSC), atomic force microscopy (AFM), micro-thermal analysis
      (microTA) and dissolution testing. Dissolution analysis showed that the use of
      supercritical CO(2) during the extrusion process resulted in a faster dissolution
      of API when compared with unassisted extrusion. The supercritical CO(2)
      incorporation also resulted in reduced viscosity during processing, therefore
      allowing for quicker throughput and productivity. The results detailed within
      this paper indicate that supercritical fluid assisted hot melt extrusion is a
      viable enhancement to conventional hot melt extrusion for the production of
      monolithic dosage forms.

PMID- 17010545
TI  - EO-9 bladder instillations: formulation selection based on stability
      characteristics and in vitro simulation studies.
AB  - A bladder instillation of EO-9 (EOquin) is currently used in phase II clinical
      trials for the treatment of superficial bladder cancer. Three alternative
      formulations were developed to improve its pharmaceutical properties and clinical
      acceptability. Freeze-dried products composed of EO-9, 2-hydroxypropyl-beta
      cyclodextrin (HPbetaCD), tri(hydroxymethyl) aminomethane (Tris), and sodium
      bicarbonate (NaHCO(3)) were tested. Selection of one formulation for further
      development was based on stability studies. These studies comprised stability of
      the freeze-dried products, stability after reconstitution and dilution and
      stability during bladder instillation in an experimental set-up. The stability
      study of the freeze-dried products showed that the formulation composed of EO
      9/HPbetaCD/Tris (4/600/1mg/vial) was most stable. After reconstitution and
      dilution all products were stable for at least 8h. The product composed of
      EO9/HPbetaCD/NaHCO(3) (4/600/20mg/vial) was the least stable product both as
      freeze-dried formulation and after reconstitution and dilution. The bladder
      instillation simulation experiment showed that all products were stable when
      mixed with urine of pH 8 and unstable in urine of pH 4 and 6. The degradation
      products formed in urine were EO-5a and EO-9-Cl. Based on these results, the
      product composed of EO-9/HPbetaCD/Tris (4/600/1mg/vial) was selected for further
      pharmaceutical development.

PMID- 17010546
TI  - Antimalarial and cytotoxic activities of ethnopharmacologically selected
      medicinal plants from South Vietnam.
AB  - Malaria is a major global public health problem and the alarming spread of drug
      resistance and limited number of effective drugs now available underline how
      important it is to discover new antimalarial compounds. An ethnopharmacological
      investigation was undertaken of medicinal plants traditionally used to treat
      malaria in the South Vietnam. Forty-nine plants were identified, 228 extracts
      were prepared and tested for their in vitro activity against Plasmodium
      falciparum, and assessed for any cytotoxicity against the human cancer cell line
      HeLa and the embryonic lung MRC5 cell line. In a first screening at a
      concentration of 10 microg/ml, 92 extracts from 46 plants showed antiplasmodial
      activity (parasite growth inhibition >30%). The IC(50) values of the most active
      extracts were determined as well as their selectivity towards Plasmodium
      falciparum in comparison to their cytotoxic effects against the human cell lines.
      Six plants showed interesting antiplasmodial activity (IC(50) ranging from 0.4 to
      8.6 microg/ml) with a good selectivity: two Menispermaceae, Arcangelisia flava
      (L.) Merr. and Fibraurea tinctoria Lour., and also Harrisonia perforata (Blanco)
      Merr. (Simaroubaceae), Irvingia malayana Oliv. ex Benn. (Irvingiaceae),
      Elaeocarpus kontumensis Gagn. (Elaeocarpaceae) and Anneslea fragrans Wall.
      (Theaceae).

PMID- 17010547
TI  - Evaluation of four digestive methods for extracting diatoms.
AB  - OBJECTIVE: To compare the merit of four digestive methods (nitric acid plus
      hydrogen peroxide, proteinase K, nitric acid in Disorganization Can and Soluene
      350) for extracting diatoms in order to choose the best digestive method for the
      diagnosis of drowning. METHODS: Liver, kidney and bone marrow of rabbits were
      minced and then digested by four digestive methods separately with the following
      indices compared: (1) time demanded for complete digestion; (2) degree of
      digestion for different tissues; (3) the reclaiming ratio of diatoms; (4) the
      degree of digestive destruction to diatoms. RESULTS: For sufficiently digesting
      the same tissue, the demanded times for the different methods ranked from the
      longest to the shortest were as follows: Soluene-350, proteinase K, nitric acid
      plus hydrogen peroxide, nitric acid in Disorganization Can. Nitric acid in
      Disorganization Can method and nitric acid plus hydrogen peroxide method digested
      the tissues more thoroughly than proteinase K, than Soluene-350 methods. For
      Cyclotella and Cybella, proteinase K method reclaimed most diatoms and nitric
      acid plus hydrogen peroxide method reclaimed less, while nitric acid in
      Disorganization Can and Soluene-350 methods reclaimed the least. For Navicula,
      the majority of diatoms could be extracted using proteinase K method, but only a
      few diatoms with other three methods. Under scanning electron microscopy (SEM),
      the structure of diatoms remained almost perfect after digestion with proteinase
      K, but destroyed to some extent with other three methods. CONCLUSION: This study
      demonstrated that different diatoms (in fresh or sea water) have different
      resistance to different digestive reagents. As far as the reliability and
      applicability of the diatom test is concerned, proteinase K method is of the best
      choice, nitric acid plus hydrogen peroxide can be its substitute. Soluene-350
      cannot be used for extracting sea water diatoms.

PMID- 17010548
TI  - Two consecutive fatal cases of acute myocardial infarction caused by free
      floating thrombus in the ascending aorta and review of literature.
AB  - Free floating thrombus in the ascending aorta is an uncommon source of acute
      myocardial infarction. We report on two cases of young women who died of acute
      myocardial infarction caused by a free floating thrombus in the sinus of Valsalva
      obstructing the coronary arteries' ostia. The first case reports on a 30-year-old
      pregnant woman who anamnestically had episodes with short loss of consciousness
      and weakness. The second case presents a 37-year-old woman suffering from
      multiple sclerosis with no previous history of thrombotic events. The review of
      literature revealed a predominance of women (eight females and three males).
      Interestingly, the coronary arteries bear no preference concerning the right
      (RCA) or left coronary artery (LCA) being more often occluded by a free floating
      thrombus. Especially, younger women (mean age 45.5 years, range 30-59 years) with
      no history of cardiac symptoms and without atherosclerotic changes seem to be
      predispositioned. The hypothesis that thrombus formation in cases without plaque
      disruption may depend on an endothelial erosion which seems to be more common in
      younger women and promoted by a hyperthrombogenic state is supported by our two
      cases. A comprehensive literature search revealed, that these are the first two
      reports on a free floating thrombus being the cause of fatal acute myocardial
      infarction in a pregnant woman, respectively, a woman suffering from multiple
      sclerosis.

PMID- 17010549
TI  - Facioscapulohumeral muscular dystrophy with severe mental retardation and
      epilepsy.
AB  - We report here a case of a 20-year-old woman with facioscapulohumeral muscular
      dystrophy (FSHD). In this patient, the involvement of facial muscle had been
      present since early childhood, but obscured due to the complication of profound
      mental retardation. Epilepsy emerged at eight years of age. Symmetrical limb
      muscle weakness appeared at 15 years of age, which progressed such that she was
      wheelchair-bound at 18 years of age. An elevated serum creatine kinase,
      predominant involvement of hamstrings, scapular and abdominal muscles, as well as
      an impaired stapedial reflex at high tune, were compatible with the clinical
      features of FSHD. The diagnosis of 4q35-FSHD was confirmed by detection of a 10kb
      EcoRI fragment with a p13E-11 probe on a Southern blot. The intellectual
      disability in this patient was the most severe of all FSHD patients reported to
      date and has hindered a correct diagnosis. This entity should be included in the
      differential diagnoses for patients with muscular symptoms and accompanying
      mental retardation.

PMID- 17010550
TI  - [Pseudomonas stutzeri osteitis: A case study].
AB  - We report a case of osteitis in a 46-year-old patient, caused by Pseudomonas
      stutzeri following an open fracture of the left femur. The patient was treated
      with 1g ceftazidime every 8 hours for two weeks combined with 160 mg/day of
      amikacin for 10 days. A second-line ofloxacin oral treatment at 400 mg/day was
      then given during 4 weeks. Surgical treatment consisted in debridement of the
      fracture region. Sterilization of the fracture region led to an osteosynthesis by
      blade plate and bone graft. The result was favorable.

PMID- 17010551
TI  - Expression of virulence-related genes by Enterococcus faecalis in response to
      different environments.
AB  - Enterococci are ubiquitous organisms used to both improve the flavor and texture
      of fermented foods, and provide protective mechanisms as either a probiotic or
      antimicrobial additive. However, two species, E. faecalis and E. faecium, are
      also associated with 10% of nosocomial infections of the bloodstream, wounds,
      urinary tract and heart. While the genes involved in the pathogenicity of these
      organisms are slowly identified along with the mechanisms behind their
      regulation, the environmental signals involved in the conversion to pathogenicity
      remain unclear. The distribution of virulence genes was determined in 13 E.
      faecalis isolates from medical, food and animal sources. Regardless of their
      source of isolation, all isolates harbored between eight and thirteen virulence
      genes. Relative differences in expression of the virulence associated genes clpP,
      clpX, gls24, agg, efaA, gelE, and cylBL(L) were examined in E. faecalis TMW 2.63
      and TMW 2.622 exposed to different environments (LB, BHI, respective
      supernatants, pig fecal extract, LB+6.5% NaCl, LB+pH5, LB+6.5% NaCl+pH5, and
      sausage medium) using RT-PCR and Lightcycler technology. Significant differences
      in expression were influenced by growth phase, environment, and isolate, which
      suggests that these three factors be taken into consideration during the
      selection of enterococci for use in foods or as probiotics rather than their
      source of isolation or set of virulence genes.

PMID- 17010553
TI  - Robustness testing of a chiral NACE method for R-timolol determination in S
      timolol maleate and uncertainty assessment from quantitative data.
AB  - A robustness test of a capillary electrophoresis method for the chiral separation
      of timolol in nonaqueous acidified media was performed. A two-level Plackett
      Burman design was applied in which one qualitative and six quantitative factors
      were examined. Resolution, migration times and relative migration times to
      pyridoxine (selected as internal standard) were examined as qualitative responses
      to evaluate electrophoretic performance. A quantitative response, the content of
      R-timolol in S-timolol maleate sample, was also considered. Even though some
      significant factor effects were observed on the qualitative responses, it was
      still possible to quantify the R-timolol in the S-timolol maleate samples
      properly. The quantitative response was not significantly affected by the
      selected factors, demonstrating the robustness of the procedure. However, the use
      of different HDMS-beta-CD batches seemed to affect both types of responses
      necessitating to introduce a warning in the procedure. Since the experiments of
      the Plackett-Burman design can be assimilated to laboratories in an
      interlaboratory study, uncertainty can be evaluated using the robustness test
      data. The robustness test was set-up in such a way that the required variances
      could be estimated.

PMID- 17010552
TI  - Evaluation of supercritical fluid technology as preparative technique of
      benzocaine-cyclodextrin complexes--comparison with conventional methods.
AB  - The objective of this study was to investigate the effect of the preparation
      method on the physico-chemical properties of complexes prepared between beta
      cyclodextrin (beta-Cyd) and benzocaine (BZC). In particular, the effectiveness of
      a new technique based on supercritical carbon dioxide (SC CO(2)) for preparing
      solid drug-cyclodextrin complexes was investigated and compared to other more
      conventional methods such as kneading (KN), co-evaporation (COE), co-grinding
      (GR) and sealed-heating (S.H.). Effects of temperature, pressure and exposure
      time on the properties of complexes prepared by SC CO(2) technology were also
      studied. The different systems were characterized by differential scanning
      calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray
      diffractometry (PXRD) and dissolution test according to the dispersed amount
      method. The co-grinding (GR) method resulted in amorphous products while other
      methods led to crystalline or partially amorphous products depending on both the
      method and its experimental conditions. SC CO(2) method revealed to be an
      effective technique for preparing solid systems between beta-cyclodextrin and
      benzocaine, avoiding the use of organic solvents (and problems of their complete
      removal) and allowing an easy scale-up of the process. As for the influence of
      the experimental conditions in promoting the solid-state drug-carrier interaction
      when using the SC CO(2) method, temperature seemed to play the major role,
      whereas pressure and exposure times had more limited effects. Dissolution tests
      confirmed a limited but favourable effect in increasing the exposure time, while
      indicated a possible interaction effect between temperature and pressure in
      influencing the dissolution performance of the final product. The best product
      obtained by the SC CO(2) method showed dissolution properties similar to those of
      the co-ground product and only slightly lower than the system obtained by sealed
      heating, which was the most effective technique.

PMID- 17010554
TI  - Impact of an Arthritis Self-Management Programme with an added exercise component
      for osteoarthritic knee sufferers on improving pain, functional outcomes, and use
      of health care services: An experimental study.
AB  - OBJECTIVE: The aim of this study was to assess the effect of an adopted Arthritis
      Self-Management Programme (ASMP) with an added exercise component among
      osteoarthritic knee sufferers in Hong Kong. METHODS: An experimental study with
      88 participants assigned to an intervention group and 94 participants to a
      control group. One hundred and forty-nine participants (81.9%) completed the 1
      week and 120 participants (65.6%) the 16 week post-intervention assessments.
      Participants in the intervention group received a 6-week ASMP with an added
      exercise component. Outcome measures included arthritic pain and fatigue rating,
      practice of light exercise routines, functional status, and number of unplanned
      arthritis-related medical consultations. To assess the programme's effect on
      outcome measures, the between-groups and within-group mean changes were compared
      using Mann-Whitney U-test and Friedman test. RESULTS: At 16 weeks, there were
      significant mean changes between groups in four outcome measures: reduction in
      arthritis pain (p=0.0001) and fatigue (p=0.008), and increased duration of weekly
      light exercise practice (p=0.0001) and knee flexion (p=0.004). The ability to
      perform daily activities and the number of unplanned arthritis-related medical
      consultations show statistically significant improvements between three time
      points within the intervention group only (p=0.0001 and p=0.005, respectively),
      but not between-groups (p=0.14 and p=0.86, respectively). Both groups apparently
      had no changes in muscle strength. CONCLUSION: Our findings suggest that the
      intervention had a positive effect in reducing pain, fatigue, knee range of
      motion, the practice of exercise routines, the number of medical consultations
      and in improving functional status and over a 16-week period. PRACTICE
      IMPLICATIONS: The self-management programme we applied took into account the
      local context and the ethnicity of the group. This process is worth further
      exploration and testing in different groups.

PMID- 17010555
TI  - Primary health care professionals' views on barriers and facilitators to the
      implementation of the Ottawa Decision Support Framework in practice.
AB  - OBJECTIVE: To describe primary health care professionals' views on barriers and
      facilitators for implementing the Ottawa Decision Support Framework (ODSF) in
      their practice. METHODS: Thirteen focus groups with 118 primary health care
      professionals were performed. A taxonomy of barriers and facilitators to
      implementing clinical practice guidelines was used to content-analyse the
      following sources: reports from each workshop, field notes from the principal
      investigator and written materials collected from the participants. RESULTS:
      Applicability of the ODSF to the practice population, process outcome
      expectation, asking patients about their preferred role in decision making,
      perception that the ODSF was modifiable, time issues, familiarity with the ODSF
      and its practicability were the most frequently identified both as barriers as
      well as facilitators. Forgetting about the ODSF, interpretation of evidence,
      challenge to autonomy and total lack of agreement with using the ODSF in general
      were identified only as barriers. Asking about values, health professional's
      outcome expectation, compatibility with the patient-centered approach or the
      evidence-based approach, ease of understanding and implementation, and ease of
      communicating the ODSF were identified only as facilitators. CONCLUSION: These
      results provide insight on the type of interventions that could be developed in
      order to implement the ODSF in academic primary care practice. PRACTICE
      IMPLICATIONS: Interventions to implement the ODSF in primary care practice will
      need to address a broad range of factors at the levels of the health
      professionals, the patients and the health care system.

PMID- 17010556
TI  - The role of culture in breast health practices among Chinese-Australian women.
AB  - OBJECTIVE: Exploring how cultural meanings of the breast impact on perceived
      images of breast cancer and breast health practices. METHODS: In-depth interviews
      were conducted with 20 Chinese-Australian women in their native language
      (Cantonese). RESULTS: The findings revealed that the meanings of the breast are
      constructed within the women's social and cultural context where breasts are
      associated with sex; and talking about, being concerned with or expressing
      curiosity about breasts is considered inappropriate. These views have a
      significant impact on (1) the way the informants viewed breast cancer; (2)
      perceptions of breast health practices; and (3) the explanations of breast cancer
      and associated risk perception. CONCLUSION: Understanding the nature of
      culturally-based barriers to utilization of breast cancer screening is the first
      step to discovering solutions for making screening tests more acceptable to women
      from other cultures. PRACTICE IMPLICATIONS: This study provides insight about
      obstacles for breast health promotion practices and for developing culturally
      appropriate health education programs and counselling strategies.

PMID- 17010557
TI  - Aggregation of qualitative studies--From theory to practice: Patient priorities
      and family medicine/general practice evaluations.
AB  - OBJECTIVE: Aggregation (i.e., meta-ethnography or meta-synthesis) of qualitative
      studies remains relatively rare and controversial. We have attempted this
      procedure within an investigation of patient priorities and evaluations of
      primary care in order to triangulate an instrument development process as well as
      explore associated dilemmas. METHODS: The procedures included a literature search
      of qualitative research on patient priorities and evaluations and creation of a
      framework for quality assessment of retrieved papers. The tool for the evaluation
      of quality in qualitative studies was piloted, refined, and applied to the
      retrieved literature. The articles were equally distributed between two teams in
      random fashion, and inter-rater agreement calculated. Finally, we formulated and
      applied a strategy for aggregation of data from included papers that allowed
      comparison to a systematic review of quantitative studies on the topic. RESULTS:
      Thirty-seven articles met inclusion criteria. Twenty-four of these articles were
      of sufficient quality to be included in the qualitative aggregation. Inter-rater
      agreement ranged from 0.22 to 0.77 and 0.38 to 0.60 for pair and assessor
      comparisons, respectively. The aggregation strategy enabled synthesis within sub
      categories of the heterogeneous papers. CONCLUSIONS: We have devised a modestly
      reliable instrument to assess the quality of qualitative work. The procedure for
      quality assessment and aggregation appears to be both feasible and potentially
      useful, though both theoretical and practical problems underline the need for
      further refinement prior to widespread utilization of this approach. PRACTICE
      IMPLICATIONS: An instrument to assess the quality of qualitative work within the
      context of aggregation efforts is described. Calculating inter-rater reliability
      in this framework can support future quality assessments. A method of breaking a
      heterogeneous collection of included papers into sub-categories to enable
      aggregation of qualitative studies is applied and demonstrates its feasibility
      and potential usefulness.

PMID- 17010558
TI  - Expression of adiponectin and its receptors (AdipoR1 and AdipoR2) in chicken
      ovary: potential role in ovarian steroidogenesis.
AB  - Adiponectin and its receptors (AdipoR1 and AdipoR2) mRNAs are expressed in
      various chicken tissues including ovary. However, the cellular expression and the
      role of adiponectin system have never been investigated in chicken ovary. Here,
      we have shown that the level of adiponectin mRNA is about 10- to 30-fold higher
      (p<0.001) in theca cells than in granulosa cells from each hierarchical yellow
      follicle studied (F4-F1). In contrast, the level of AdipoR1 mRNA expression was
      about two-fold lower in theca cells than in granulosa cells (p<0.05) whereas
      those of AdipoR2 was similar in both ovarian cells. Whereas expression of
      adiponectin mRNA increased with follicular differentiation in theca cells, it
      decreased in granulosa cells. In contrast, mRNA expression of AdipoR1 and AdipoR2
      in both theca and granulosa cells remained stable during yellow follicle
      development. To determine whether adiponectin is involved in the ovarian
      steroidogenesis, LH (100 ng/ml)-, FSH (100 ng/ml)- and IGF-1 (100 ng/ml)-induced
      progesterone production was measured in absence or presence of human recombinant
      adiponectin (10 microg/ml) for 36 h in cultured granulosa cells from F1, F2 and
      mixed F3 and F4 follicles. In absence of LH, FSH and IGF-1, adiponectin treatment
      had no effects on progesterone production whatever vitollegenic follicle studied.
      However, it increased by about two-fold IGF-1-induced progesterone secretion in
      F2 and F3/4 follicles whereas it halved progesterone production in response to
      gonadotropins (LH and FSH) in F3/4 follicles. Thus, in chicken, adiponectin,
      mainly expressed in theca cells, could exert paracrine or autocrine effect on the
      ovarian steroidogenesis.

PMID- 17010559
TI  - Production of inhibin A and inhibin B in boars: changes in testicular and
      circulating levels of dimeric inhibins and characterization of inhibin forms
      during testis growth.
AB  - We investigated the production of inhibin in boars from the infantile to pubertal
      periods by: (1) measurement of testicular and circulating levels of inhibin, (2)
      characterization of inhibin forms and (3) localization of inhibin alpha subunits
      in the testis. Total inhibin levels in the testis increased until 8 weeks of age
      but then declined to much lower values at 15 weeks. Testicular inhibin A and
      inhibin B were high until 8 weeks. Circulating levels of total inhibin and
      inhibin A were also high until 8 weeks, then declined from 10 weeks; inhibin B
      was not detected, because of low sensitivity of the inhibin B assay. Analyses of
      inhibin A and inhibin B levels in the eluted fractions obtained from testes after
      immunoaffinity chromatography and SDS-PAGE showed the presence of a peak of
      approximately 45 kDa until 10 weeks of age. As the boars aged, the levels of
      inhibin A and inhibin B increased in the molecular weight region of 29-31 kDa.
      The fractions corresponding to 29 and 30 kDa suppressed FSH release from rat
      pituitary cells, but the 45 kDa fraction had no FSH-suppressing activity. Total
      amounts of inhibin A isolated from the SDS gels were similar to those of inhibin
      B until 10 weeks of age, but were three times higher than those of inhibin B
      between 15 and 25 weeks. Further fractionation by reverse phase high-performance
      liquid chromatography revealed that the 29-31 kDa immunoreactive material was
      composed of mature forms of inhibin A and inhibin B, in addition to a 26 kDa
      alpha monomer. Immunohistochemistry indicated that positive immunostaining for
      the alpha subunits was observed in Sertoli cells from the infantile to pubertal
      periods. Elongated spermatids also showed positive signals at age 25 weeks. These
      results clearly indicated that: (1) the boar testis has the ability to produce
      inhibin A and inhibin B during the infantile period but inhibin A is the
      predominant form towards puberty and (2) the molecular weight forms of inhibin
      and the sites of production of inhibin change with testicular development.

PMID- 17010560
TI  - [Haemodynamic profile in paraphenylene-diamine poisoning].

PMID- 17010561
TI  - [Epidemiology of locoregional analgesia in a paediatric anaesthesia unit].

PMID- 17010562
TI  - [Spreading infectious endocarditis: an example of vascularitis].

PMID- 17010563
TI  - Silent infarct? It depends were you seat.

PMID- 17010564
TI  - [Anaesthesia for craniosynostosis: increase water and electrolyte therapy].

PMID- 17010565
TI  - Molecular genetic analyses of human endogenous retroviral elements belonging to
      the HERV-P family in primates, human tissues, and cancer cells.
AB  - Human endogenous retroviral sequences family P (HERV-P) proviral sequences have
      been located within the human genome. Here, we identify and analyze novel
      putative structural genes of HERV-P in primates, human tissues, and cancer cells
      with an aim toward better understanding their evolutionary relationships and
      transcriptional potential. The expression pattern of HERV-P structural genes
      indicates that they are actively amplified in human tissues and widely expressed
      in cancer cells, suggesting a potential role in carcinogenesis. Phylogenetic
      analyses suggest that the HERV-P family may be divided into two distinct
      categories that arose during primate evolution via active gene duplication. Taken
      together, our data provide a better understanding of the dynamic evolutionary
      features and potential functional roles of the HERV-P gene family.

PMID- 17010566
TI  - Designing new microsatellite markers for linkage and population genetic analyses
      in rhesus macaques and other nonhuman primates.
AB  - Identification of polymorphic microsatellite loci in nonhuman primates is useful
      for various biomedical and evolutionary studies of these species. Prior methods
      for identifying microsatellites in nonhuman primates are inefficient. We describe
      a new strategy for marker development that uses the available whole genome
      sequence for rhesus macaques. Fifty-four novel rhesus-derived microsatellites
      were genotyped in large pedigrees of rhesus monkeys. Linkage analysis was used to
      place 51 of these loci into the existing rhesus linkage map. In addition, we find
      that microsatellites identified this way are polymorphic in other Old World
      monkeys such as baboons. This approach to marker development is more efficient
      than previous methods and produces polymorphisms with known locations in the
      rhesus genome assembly. Finally, we propose a nomenclature system that can be
      used for rhesus-derived microsatellites genotyped in any species or for novel
      loci derived from the genome sequence of any nonhuman primate.

PMID- 17010567
TI  - Combined-cross analysis of genome-wide linkage scans for experimental autoimmune
      encephalomyelitis in rat.
AB  - Unbiased genetic analysis of experimental autoimmune encephalomyelitis (EAE) can
      provide insights into the pathogenesis of multiple sclerosis. To date five genome
      wide scans using F2 crosses between different inbred rats have been performed
      with the aim of defining EAE-regulating quantitative trait loci (QTLs) as the
      starting point for identification of the underlying genes. We here report the
      first combined-cross analysis of three F2 crosses previously performed in our
      group. The majority of QTLs was shared between the different strain combinations
      and was therefore reproduced by the combined-cross analysis. Consequently,
      combined-cross analysis improved the power to detect QTLs with modest effects and
      narrowed QTL confidence intervals. The findings also demonstrate a lack of power
      in previous F2 crosses and encourage future use of larger populations. Moreover,
      the allelic states of shared QTLs could be established, thus providing critical
      information for narrowing QTLs and identifying the key polymorphism by subsequent
      haplotype analysis.

PMID- 17010568
TI  - Sick building syndrome (SBS) and exposure to water-damaged buildings: time series
      study, clinical trial and mechanisms.
AB  - Occupants of water-damaged buildings (WDBs) with evidence of microbial
      amplification often describe a syndrome involving multiple organ systems,
      commonly referred to as "sick building syndrome" (SBS), following chronic
      exposure to the indoor air. Studies have demonstrated that the indoor air of WDBs
      often contains a complex mixture of fungi, mycotoxins, bacteria, endotoxins,
      antigens, lipopolysaccharides, and biologically produced volatile compounds. A
      case-series study with medical assessments at five time points was conducted to
      characterize the syndrome after a double-blinded, placebo-controlled clinical
      trial conducted among a group of study participants investigated the efficacy of
      cholestyramine (CSM) therapy. The general hypothesis of the time series study was
      that chronic exposure to the indoor air of WDBs is associated with SBS.
      Consecutive clinical patients were screened for diagnosis of SBS using criteria
      of exposure potential, symptoms involving at least five organ systems, and the
      absence of confounding factors. Twenty-eight cases signed voluntary consent forms
      for participation in the time-series study and provided samples of microbial
      contaminants from water-damaged areas in the buildings they occupied. Twenty-six
      participants with a group-mean duration of illness of 11 months completed
      examinations at all five study time points. Thirteen of those participants also
      agreed to complete a double-blinded, placebo-controlled clinical trial. Data from
      Time Point 1 indicated a group-mean of 23 out of 37 symptoms evaluated; and
      visual contrast sensitivity (VCS), an indicator of neurological function, was
      abnormally low in all participants. Measurements of matrix metalloproteinase 9
      (MMP9), leptin, alpha melanocyte stimulating hormone (MSH), vascular endothelial
      growth factor (VEGF), immunoglobulin E (IgE), and pulmonary function were
      abnormal in 22, 13, 25, 14, 1, and 7 participants, respectively. Following 2
      weeks of CSM therapy to enhance toxin elimination rates, measurements at Time
      Point 2 indicated group-means of 4 symptoms with 65% improvement in VCS at mid
      spatial frequency-both statistically significant improvements relative to Time
      Point 1. Moderate improvements were seen in MMP9, leptin, and VEGF serum levels.
      The improvements in health status were maintained at Time Point 3 following a 2
      week period during which CSM therapy was suspended and the participants avoid re
      exposure to the WDBs. Participants reoccupied the respective WDBs for 3 days
      without CSM therapy, and all participants reported relapse at Time Point 4. The
      group-mean number of symptoms increased from 4 at Time Point 2 to 15 and VCS at
      mid-spatial frequency declined by 42%, both statistically significant differences
      relative to Time Point 2. Statistically significant differences in the group-mean
      levels of MMP9 and leptin relative to Time Point 2 were also observed. CSM
      therapy was reinstated for 2 weeks prior to assessments at Time Point 5.
      Measurements at Time Point 5 indicated group-means of 3 symptoms and a 69%
      increase in VCS, both results statistically different from those at Time Points 1
      and 4. Optically corrected Snellen Distance Equivalent visual acuity scores did
      not vary significantly over the course of the study. Group-mean levels of MMP9
      and leptin showed statistically significant improvement at Time Point 5 relative
      to Time Points 1 and 4, and the proportion of participants with abnormal VEGF
      levels was significantly lower at Time Point 5 than at Time Point 1. The number
      of participants at Time Point 5 with abnormal levels of MMP9, leptin, VEGF, and
      pulmonary function were 10, 10, 9, and 7, respectively. The level of IgE was not
      re-measured because of the low incidence of abnormality at Time Point 1, and MSH
      was not re-measured because previously published data indicated a long time
      course for MSH improvement. The results from the time series study supported the
      general study hypothesis that exposure to the indoor air of WDBs is associated
      with SBS. High levels of MMP9 indicated that exposure to the complex mixture of
      substances in the indoor air of the WDBs triggered a pro-inflammatory cytokine
      response. A model describing modes of action along a pathway leading to biotoxin
      associated illness is presented to organize current knowledge into testable
      hypotheses. The model links an inflammatory response with tissue hypoxia, as
      indicated by abnormal levels of VEGF, and disruption of the proopiomelanocortin
      pathway in the hypothalamus, as evidenced by abnormalities in leptin and MSH
      levels. Results from the clinical trial on CSM efficacy indicated highly
      significant improvement in group-mean number of symptoms and VCS scores relative
      to baseline in the 7 participants randomly assigned to receive 2 weeks of CSM
      therapy, but no improvement in the 6 participants assigned placebo therapy during
      that time interval. However, those 6 participants also showed a highly
      significant improvement in group-mean number of symptoms and VCS scores relative
      to baseline following a subsequent 2-week period of CSM therapy. Because the only
      known benefit of CSM therapy is to enhance the elimination rates of substances
      that accumulate in bile by preventing re-absorption during enterohepatic re
      circulation, results from the clinical trial also supported the general study
      hypothesis that SBS is associated with exposure to WDBs because the only relevant
      function of CSM is to bind and remove toxigenic compounds. Only research that
      focuses on the signs, symptoms, and biochemical markers of patients with
      persistent illness following acute and/or chronic exposure to WDBs can further
      the development of the model describing modes of action in the biotoxin
      associated pathway and guide the development of innovative and efficacious
      therapeutic interventions.

PMID- 17010569
TI  - Assessment of the formant frequencies in normal and laryngectomized individuals
      using linear predictive coding.
AB  - The objective of this study was to assess the difference in voice quality as
      defined by acoustical analysis using sustained vowel in laryngectomized patients
      in comparison with normal volunteers. This was designed as a retrospective single
      center cohort study. An adult tertiary referral unit formed the setting of this
      study. Fifty patients (40 males) who underwent total laryngectomy and 31 normal
      volunteers (18 male) participated. Group comparisons with the first three formant
      frequencies (F1, F2, and F3) using linear predictive coding (LPC) (Laryngograph
      Ltd, London, UK) was performed. The existence of any significant difference of
      F1, F2, and F3 between the two groups using the sustained vowel /i/ and the
      effects of other factors namely, tumor stage (T), chemoradiotherapy,
      pharyngectomy, cricothyroid myotomy, closure of pharyngoesophageal segment, and
      postoperative complication were analyzed. Formant frequencies F1, F2, and F3 were
      significantly different in male laryngectomees compared to controls: F1 (P<0.001,
      Mann-Whitney U test), F2 (P<0.001, Student's t test), and F3 (P=0.008, Student's
      t test). There was no significant difference between females in both groups for
      all three formant frequencies. Chemoradiotherapy and postoperative complications
      (pharyngocutaneous fistula) caused a significantly lower formant F1 in men, but
      showed little effect in F2 and F3. Laryngectomized males produced significantly
      higher formant frequencies, F1, F2, and F3, compared to normal volunteers, and
      this is consistent with literature. Chemoradiotherapy and postoperative
      complications significantly influenced the formant scores in the laryngectomee
      population. This study shows that robust and reliable data could be obtained
      using electroglottography and LPC in normal volunteers and laryngectomees using a
      sustained vowel.

PMID- 17010570
TI  - The interaction of implicit learning, explicit hypothesis testing learning and
      implicit-to-explicit knowledge extraction.
AB  - To further explore the interaction between the implicit and explicit learning
      processes in skill acquisition (which have been tackled before, e.g. in [Sun, R.,
      Merrill, E., & Peterson, T. (2001). From implicit skill to explicit knowledge: A
      bottom-up model of skill learning. Cognitive Science, 25(2), 203-244; Sun, R.,
      Slusarz, P., & Terry, C. (2005). The interaction of the explicit and the implicit
      in skill learning: A dual-process approach. Psychological Review, 112(1), 159
      192]), this paper explores details of the interaction of different learning
      modes: implicit learning, explicit hypothesis testing learning, and implicit-to
      explicit knowledge extraction. Contrary to the common tendency in the literature
      to study each type of learning in isolation, this paper highlights the
      interaction among them and various effects of the interaction on learning,
      including the synergy effect. This work advocates an integrated model of skill
      learning that takes into account both implicit and explicit learning processes;
      moreover, it also uniquely embodies a bottom-up (implicit-to-explicit) learning
      approach in addition to other types of learning. The paper shows that this model
      accounts for various effects in the human behavioural data from the psychological
      experiments with the process control task, in addition to accounting for other
      data in other psychological experiments (which has been reported elsewhere). The
      paper shows that to account for these effects, implicit learning, bottom-up
      implicit-to-explicit extraction and explicit hypothesis testing learning are all
      needed.

PMID- 17010571
TI  - Perception through visuomotor anticipation in a mobile robot.
AB  - Several scientists suggested that certain perceptual qualities are based on
      sensorimotor anticipation: for example, the softness of a sponge is perceived by
      anticipating the sensations resulting from a grasping movement. For the
      perception of spatial arrangements, this article demonstrates that this concept
      can be realized in a mobile robot. The robot first learned to predict how its
      visual input changes under movement commands. With this ability, two perceptual
      tasks could be solved: judging the distance to an obstacle in front by 'mentally'
      simulating a movement toward the obstacle, and recognizing a dead end by
      simulating either an obstacle-avoidance algorithm or a recursive search for an
      exit. A simulated movement contained a series of prediction steps. In each step,
      a multilayer perceptron anticipated the next image, which, however, became
      increasingly noisy. To denoise an image, it was split into patches, and each
      patch was projected onto a manifold obtained by modelling the density of the
      distribution of training patches with a mixture of Gaussian functions.

PMID- 17010572
TI  - Salvage neck dissections in oral and oropharyngeal squamous cell carcinoma:
      histological features in relation to disease category.
AB  - The histological findings in a series of 37 salvage neck dissections from
      patients who had an oral or oropharyngeal squamous cell carcinoma managed
      initially by primary surgery with or without neck dissection, and without
      postoperative radiotherapy, are described. None of the cases had an intraoral
      relapse. Pathological stage N2 or N3 disease was seen in 87% of the 15 salvage
      dissections from 'wait and watch' necks, 100% of the 10 salvage dissections of
      contralateral necks and 50% of the 12 salvage dissections of operated necks. The
      typical 'inverted-cone' pattern of metastasis was seen in 87% of 'wait and watch'
      necks. Skip or non-contiguous metastases to level III/IV accounted for relapse in
      30% of the contralateral and 66% of the operated necks. The median time interval
      between original surgery and the salvage neck dissection was 15 months (range 1
      48 months). In at least 15% of cases, the short time interval coupled with the
      histopathological features suggested that the metastatic disease suddenly became
      more rapidly progressive following removal of the primary tumour.

PMID- 17010573
TI  - Neural correlates of working memory dysfunction in first-episode schizophrenia
      patients: an fMRI multi-center study.
AB  - Working memory dysfunction is a prominent impairment in patients with
      schizophrenia. Our aim was to determine cerebral dysfunctions by means of
      functional magnetic resonance imaging (fMRI) in a large sample of first-episode
      schizophrenia patients during a working memory task. 75 first-episode
      schizophrenia patients and 81 control subjects, recruited within a multi-center
      study, performed 2- and 0-back tasks while brain activation was measured with
      fMRI. In order to guarantee comparability between data quality from different
      scanners, we developed and adopted a standardized, fully automated quality
      assurance of scanner hard- and software as well as a measure for in vivo data
      quality. After these quality-control measures had been implemented, 48 patients
      and 57 controls were included in the final analysis. During attention-related
      processes, even when the performance between patients and controls was
      comparable, there was a recognizable emergence of cerebral dysfunctions with
      hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior
      temporal cortex and in the thalamus. During working memory performance, parietal
      hypoactivations, especially in the precuneus, were prominent and were accompanied
      by poorer performance in patients. A hyperfrontality emerged in the ventrolateral
      prefrontal cortex. Hence, results point to a dysfunctional ventrolateral
      prefrontal-parietal network during working memory in patients, suggesting
      impairments in basic functions such as retrieval, storage and maintenance. The
      brain activation pattern of this large and significant sample of first-episode
      schizophrenia patients indicates an imbalanced system failing to adjust the
      amount of brain activity required in the cerebral network involved in attention
      and working memory.

PMID- 17010574
TI  - The 2',3'-cyclic nucleotide 3'-phosphodiesterase and oligodendrocyte lineage
      transcription factor 2 genes do not appear to be associated with schizophrenia in
      the Japanese population.
AB  - Several lines of evidence suggest that disturbance of myelin-related genes is
      associated with the etiology of schizophrenia. Recently, the 2',3'-cyclic
      nucleotide 3'-phosphodiesterase (CNP) gene and the oligodendrocyte lineage
      transcription factor 2 (OLIG2) gene were reported to be related to the
      development of schizophrenia, based on the results of genetic association and
      microarray studies. In the present study, no significant association with
      schizophrenia was observed by single-marker or haplotype analysis for 6 tag SNPs
      of these genes (759 cases, 757 controls). These findings suggest that CNP and
      OLIG2 are unlikely to be related to the development of schizophrenia in the
      Japanese population.

PMID- 17010575
TI  - Visual scan paths in young patients with schizophrenia, healthy siblings and
      controls.

PMID- 17010576
TI  - Denaturation of jack-bean urease by sodium n-dodecyl sulphate: a kinetic study
      below the critical micelle concentration.
AB  - Kinetics of urease denaturation by anionic surfactant (sodium n-dodecyl sulphate,
      SDS) at concentrations below the critical micelle concentration (CMC) is
      investigated spectrophotometrically at neutral pH and the corresponding two-phase
      kinetic parameters of the process are estimated from a three-state reversible
      process using a binomial exponential relation based on the relaxation time method
      as: Using a prepared computer program, the experimental data are properly fitted
      into a binomial exponential relation, considering a two-phase denaturation
      pathway including a kinetically stable folded intermediate formed at SDS
      concentration of 1.1 mM. Forward and backward rate constants are estimated as:
      k(1)=0.2141+/-4.5 x 10(-3), k(2)=5.173 x 10(-3)+/-8.3 x 10(-5), k(-1)=0.09432+/
      3.6 x 10(-4) and k(-2)=2.079 x 10(-3)+/-5.6 x 10(-5)s(-1) for the proposed
      mechanism. The rate-limiting step as well as the reaction coordinates in the
      denaturation mechanism are established. The mechanism involves formation of a
      kinetically stable folded native like intermediate through the electrostatic
      interactions. The intermediate was found to be more stable even than the native
      form (by about 9 kJmol(-1)) and still hexamer, because no loss of amplitude was
      observed. Electrophoresis experiments on the native and surfactant/urease
      complexes indicated a higher mobility for the kinetically folded native like
      intermediate.

PMID- 17010578
TI  - Semmelweis' present day follow-up: Updating bacterial sampling and enrichment in
      clinical hygiene.
AB  - Potentially dangerous antibiotic resistant contaminants have permanently
      penetrated at least well-off western populations. The danger is so evident that
      some hospitals have started to refuse accepting patients who carry such bacteria.
      Sampling and enrichment measures in hygiene monitoring must be updated as they
      are corner stones in handling the problems and safeguarding the health care
      units. Their patients, when exposed to microorganisms are strenuous to treat.
      Sometimes even this fails, if the infections are spreading in weakened patients.
      The present review summarizes currently used technologies and the abilities of
      bacteria to avoid detection. Improved protocols on environmental monitoring in
      healthcare units are required. They should be comparable with contamination
      control in industries. Actually these measures in health care should be even
      stricter because human lives are directly endangered as the resistance of
      especially elderly patients is low.

PMID- 17010577
TI  - LY294,002, a specific inhibitor of PI3K/Akt kinase pathway, antagonizes P
      glycoprotein-mediated multidrug resistance.
AB  - The transmembrane transport pump P-glycoprotein (P-gp) causes the efflux of
      chemotherapeutic agents from cells and is an important system that secures
      multidrug resistance (MDR) of neoplastic cells. In the present study drug
      sensitive L1210 and multidrug resistant L1210/VCR mouse leukemic cell lines were
      used as an experimental model. We found that LY 294,002, a specific inhibitor of
      PI3K/Akt kinase pathway, reduced the degree of vincristine resistance in
      L1210/VCR cells significantly and in a concentration-dependent manner. This was
      accompanied by decrease in IC(50) value to vincristine from 3.195+/-0.447 to
      1.898+/-0.676 micromol/l for 2 micromol/l, to 0.947+/-0.419 micromol/l for 4
      micromol/l, and to 0.478+/-0.202 micromol/l for 8 micromol/l LY294,002. The
      IC(50) value of sensitive cells for vincristine was about 0.010 micromol/l. FACS
      analysis of the proportion of cells in apoptosis or necrosis by annexin-V
      apoptosis kit showed the following: (i) vincristine-induced apoptosis in
      resistant cell to a much lower extent than in sensitive cells; (ii) LY294,002
      alone did not induce apoptosis or necrosis in both sensitive and resistant cells;
      (iii) LY294,002 applied together with vincristine significantly increased the
      number of apoptotic cells. Transport activity of P-gp in resistant cells was
      monitored using calcein/AM as substrate and was depressed by LY294,002 in a
      concentration dependent manner. Significant differences in calcein retention were
      not observed when cells were preincubated with LY294,002 at different times from
      0.5 to 24h. Sensitive and resistant cells contain similar amounts of uncleaved
      (i.e., unactivated) caspase-3 but in latter cells the activation of caspase-3 by
      proteolytic cleavage was decreased. The reversal of vincristine resistance by
      LY294,002 was associated with marked activation of caspase-3. Western blot
      analysis revealed that the development of MDR phenotype in L1210/VCR cells was
      also associated with increased level of Bcl-2 protein. All the above findings
      point to the possible involvement of PI3K/Akt kinase pathway in modulation of P
      gp mediated multidrug resistance in L1210/VCR mouse leukemic cell line. MDR
      reversal effect of LY294,002 is accompanied with this compound's influence on
      vincristine-induced apoptosis.

PMID- 17010579
TI  - [Paediatric case report of an acquired autoimmune thrombotic thrombocytopenic
      purpura].
AB  - Thrombotic thrombocytopenic purpura (TTP), when accompanied by regenerative
      anaemia with schizocytosis, thrombopenia and neurological manifestations, is a
      disease whose main characteristic is the absence of the von Willebrand factor
      (vWF) cleaving protease. The two types of TTP are distinguishable by the presence
      or absence of antiprotease inhibitors, which are, respectively, either acquired
      or constitutional. The acquired autoimmune form is most frequently observed in
      adults. OBSERVATION: An adolescent with a previous history of moderate, isolated
      thrombopenia first showed symptoms of TTP at the age of 14. Positive antiprotease
      inhibitors in combination with a degeneration of protease activity confirmed the
      diagnosis of acquired autoimmune TTP. A treatment consisting of daily plasma
      exchange led to rapid improvement; however, a failed attempt to space out plasma
      exchanges necessitated the introduction of 4 weekly injections of Rituximab
      beginning on day 40, which was successful. Indeed, since the second injection of
      Rituximab on day 51, the number of platelets stabilized at a normal level,
      thereby allowing for the complete cessation of plasma exchange. At this writing -
      day 89 - the patient remains in persistent remission. CONCLUSION: Given the
      different therapeutic and prognostic implications of the 2 types of TTP in child
      patients, it is mandatory to end at an accurate biological diagnosis: whereas the
      constitutional form is effectively treated with plasma injections, the acquired
      form, while initially requiring plasma exchange, often necessitates the use of
      immunosuppressors during acute or relapse phase. The present study concerns a
      paediatric case of acquired TTP treated successfully with Rituximab during an
      acute dependant phase.

PMID- 17010580
TI  - Anatomical sketch understanding: recognizing explicit and implicit structure.
AB  - OBJECTIVE: Sketching is ubiquitous in medicine. Physicians commonly use sketches
      as part of their note taking in patient records and to help convey diagnoses and
      treatments to patients. Medical students frequently use sketches to help them
      think through clinical problems in individual and group problem solving.
      Applications ranging from automated patient records to medical education software
      could benefit greatly from the richer and more natural interfaces that would be
      enabled by the ability to understand sketches. In this paper we take the first
      steps toward developing a system that can understand anatomical sketches.
      METHODS: Understanding an anatomical sketch requires the ability to recognize
      what anatomical structure has been sketched and from what view (e.g. parietal
      view of the brain), as well as to identify the anatomical parts and their
      locations in the sketch (e.g. parts of the brain), even if they have not been
      explicitly drawn. We present novel algorithms for sketch recognition and for part
      identification. We evaluate the accuracy of the recognition algorithm on sketches
      obtained from medical students. We evaluate the part identification algorithm by
      comparing its results to the judgment of an experienced physician. RESULTS: The
      sketch recognition algorithm achieves a recognition accuracy of 75.5%, far above
      the baseline random classification accuracy of 6.7%. Comparison of the results of
      the part identification algorithm with the judgment of an experienced physician
      shows close agreement in terms of location, orientation, size, and shape of the
      identified parts. CONCLUSIONS: The performance of our prototype in terms of
      accuracy and running time provides strong evidence that development of robust
      sketch understanding systems for medical domains is an attainable goal. Further
      work needs to be done to extend the approach to sketches containing multiple and
      partial anatomical structures, as well as to be able to interpret sketch
      annotations.

PMID- 17010581
TI  - Association of methylenetetrahydrofolate reductase (C677T) polymorphism with
      hyperuricemia.
AB  - BACKGROUND AND AIMS: Homozygosity for the thermolabile variant of 5,10-methylene
      tetrahydrofolate reductase (C677T) has been suggested to be positively associated
      with the risk of vascular disease and neural tube defects. In addition, recent
      studies have suggested that elevated serum uric acid predicts ischemic heart
      disease, and epidemiological data on ethnic groups have suggested that genetic
      factors are determinants of serum uric acid levels. In this study, we tested the
      hypothesis that 5,10-methylenetetrahydrofolate reductase (C677T) polymorphism may
      be associated with hyperuricemia. METHODS AND RESULTS: Samples from 518 healthy
      individuals (268 men and 250 women) were analyzed for MTHFR genotyping and serum
      uric acid. The participants were categorized to homozygous wild type (CC),
      heterozygous for wild type and thermolabile (CT), or homozygous for the
      thermolabile (TT) variant. Serum uric acid was significantly higher in males and
      females with TT genotype than those with either CC or CT genotype (p=0.0001,
      ANOVA). Univariate and multivariate analysis showed that 5,10
      methylenetetrahydrofolate reductase (C677T) polymorphism was a strong correlate
      and predictor of uric acid in males (r=0.28, p=0.0001, beta=0.673, p=<0.001) and
      in females (r=0.27, p=0.0001, beta=0.599, p=<0.001). Odds ratio analysis has also
      shown that the risk of hyperuricemia was greater in males (OR 3.1, CI 1.8-5.2,
      p=0.001) and females (OR 3.3, CI 1.9-5.7, p=<0.001) with CT genotypes and in
      males (OR 3.7, CI 1.3-10.7, p=0.014) and females (OR 3.2, CI 1.1-9.7, p=0.032)
      with TT genotypes than in those with CC genotypes. CONCLUSION: Results from this
      study suggest that mutation of 5-MTHFR C677T contributes to the higher uric acid
      levels in both males and females and may be a risk factor for hyperuricemia.

PMID- 17010582
TI  - Morphology of protein particles produced by spray freezing of concentrated
      solutions.
AB  - The mechanisms for the formation of high surface area lysozyme particles in spray
      freezing processes are described as a function of spray geometry and atomization,
      solute concentration and the calculated cooling rate. In the spray freeze-drying
      (SFD) process, droplets are atomized into a gas and then freeze upon contact with
      a liquid cryogen. In the spray freezing into liquid (SFL) process, a solution is
      sprayed directly into the liquid cryogen below the gas-liquid meniscus. A wide
      range of feed concentrations is examined for two cryogens, liquid nitrogen (LN2)
      and isopentane (i-C5). The particle morphologies are characterized by SEM
      micrographs and BET measurements of specific surface area. As a result of boiling
      of the cryogen (Leidenfrost effect), the cooling rate for SFL into LN2 is several
      orders of magnitude slower than for SFL into i-C5 and for SFD in the case of
      either LN2 or i-C5. For 50 mg/mL concentrated feed solutions, the slower cooling
      of SFL into LN2 leads to a surface area of 34 m(2)/g. For the other three cases
      with more rapid cooling rates, surface areas were greater than 100 m(2)/g. The
      ability to adjust the cooling rate to vary the final particle surface area is
      beneficial for designing particles for controlled release applications.

PMID- 17010583
TI  - Purification and properties of an unusual UDP-glucose dehydrogenase, NADPH
      dependent, from Xanthomonas albilineans.
AB  - Xanthomonas albilineans produces a UDP-glucose dehydrogenase growing on sucrose.
      The enzyme oxidizes UDP-glucose to UDP-glucuronic acid by using molecular oxygen
      and NADPH. Kinetics of enzymatic oxydation of NADPH is linearly dependent on the
      amount of oxygen supplied. The enzyme has been purified at homogeneity. The value
      of pI of the purified enzyme is 8.98 and its molecular mass has been estimated as
      about 14 kDa. The enzyme shows a michaelian kinetics for UDP-glucose
      concentrations. The value of K(m) for UDP-glucose is 0.87 mM and 0.26 mM for
      NADPH, although the enzyme has three different sites to interact with NADPH. The
      enzyme is inhibited by UDP-glucose concentrations higher than 1.3 mM. N-Terminal
      sequence has been determined as IQPYNH.

PMID- 17010584
TI  - Matrix metalloproteinase 9 (MMP-9) is upregulated during scarless wound healing
      in athymic nude mice.
AB  - Cutaneous wound healing is associated with migratory and remodeling events that
      require the action of matrix metalloproteinases (MMPs) and their tissue
      inhibitors (TIMPs). Differences in their expressions were observed during scar
      forming and scar-free skin wound healing. We previously found that athymic nude
      mice are exceptional among mature mammals in their ability to heal injured skin
      scarlessly. The present study was undertaken to determine whether the modulation
      of MMP-2 and MMP-9 expression during scarless healing in nude mice was different
      from scar-forming animals. Full thickness skin wounds were made into the back of
      nude, wild-type controls (C57BL/6J), immunodeficient SCID and Rag, thymectomized
      neonates and adults, and cyclosporin A treated mice. Post-injured skin tissues
      were harvested at Day 7 and 24 after injury. Quantitative RT-PCR, Western blot,
      gelatin zymography and immunohistochemical assays were performed. Our results
      show that MMP-2 protein was high but similarly expressed in all post-injured
      animals on Day 7 after injury. Late phase (Day 24) of wound repair was
      characterized by a decrease in mRNA and protein expression and a decrease in
      gelatinolytic activity of MMP-2 in all post-injured samples. On the contrary,
      high (p < 0.001) levels of mRNA expression, prominent pro-and active forms of MMP
      9 and cells immunopositive for MMP-9 were present exclusively in the post-injured
      tissues from nude mice on Day 24 after wounding. This data suggest that MMP-9
      expression in the remodeling phase of wound healing in nude mice could be a major
      component of their ability for scar-free healing.

PMID- 17010585
TI  - Novel vaccines and adjuvants for allergen-specific immunotherapy.
AB  - Advances in genetic engineering and biotechnology, in parallel to increased
      understanding of disease processes and mechanisms of protective immunity, have
      facilitated the development of novel rational vaccination concepts for allergy.
      The spectrum ranges from utilizing recombinant proteins, peptides, new adjuvants,
      immunomodulatory therapy and DNA vaccines, to use of new application routes for
      both prophylaxis and treatment of allergic disease. New therapeutic concepts
      based on patient-tailored immunotherapy using recombinant allergens, anti-IgE and
      sublingual immunotherapies are slowly moving from the bench to the clinics. The
      additive value of new treatments above existing therapies must be, however,
      focused on the improvement of efficacy for long-term cure and increased patient
      compliance to warrant a broad applicability that has to compete with the
      symptomatic control of allergic and asthmatic diseases of currently available
      drugs.

PMID- 17010586
TI  - Immunoregulation by targeting T cells in the treatment of allergy and asthma.
AB  - T-cell responses to allergens are crucial in determining the choice between
      health and disease. Th2 responses drive synthesis of IgE and the recruitment,
      maturation, survival and effector function of accessory cells such as
      eosinophils, basophils and mast cells. Allergen-specific strategies for targeting
      T-cell responses in established allergic diseases have been employed with success
      for almost a century. Recently, new insight into the mechanism of action of such
      approaches has revealed modulation of the delicate and complex regulatory
      mechanisms including suppression of Th2 responses through antagonistic Th1
      responses and regulation through IL-10 and TGFbeta production.

PMID- 17010587
TI  - When T cells recognize a pattern, they might cause trouble.
AB  - The mechanisms of self and non-self discrimination by T cells remain a
      fascinating topic for immunologists. How the immune system achieves protection of
      the host against an ever-changing realm of pathogens using a rather limited
      repertoire of T-cell receptors and at the same time avoids inflicting damage
      against its own tissues is equally puzzling. Although a better understanding of
      these questions has come from studies of the extent of cross reactivity of T-cell
      clones specific for foreign or self antigens, and also from examination of the
      different antigen avidities by which they recognize either type of antigen, many
      details are still lacking. Recently, there has been investigation into how T
      cells of the adaptive immune system can recognize functional protein domains or
      amino acid patterns. This type of T-cell reactivity is reminiscent of the pattern
      recognition that is firmly established as an important function of innate immune
      receptors such as Toll-like receptors. Many functional protein domains are
      conserved in evolution and are shared by a wide spectrum of pathogens, as well as
      by proteins of animals and humans. Hence, pattern recognition by adaptive immune
      cells might represent an efficient mechanism for host protection by the above
      mentioned limited number of T-cell receptors. However, the fact that such
      functional domains occur so frequently in nature also implies that pattern
      recognition by T cells might cause autoimmunity, and recent data support this
      hypothesis.

PMID- 17010588
TI  - Chemokines, mononuclear cells and the nervous system: heaven (or hell) is in the
      details.
AB  - Chemokines and their receptors are essential elements in leukocyte trafficking
      during health and disease. There are three (or more) distinct routes of leukocyte
      entry into the central nervous system (CNS), and molecular mechanisms of
      physiological and neuroinflammatory leukocyte recruitment to the CNS are slowly
      coming into view. Migration of immune cells into cerebrospinal fluid supports CNS
      immunosurveillance. Current knowledge of the trafficking determinants that direct
      the leukocyte recruitment in CNS pathology relies in large part on studies of
      multiple sclerosis and its models including experimental autoimmune
      encephalomyelitis. Overlapping molecular signals are responsible for the
      migration of specific cells into the CNS during pathological inflammation and
      host defense, raising challenges and opportunities for therapeutic manipulation.

PMID- 17010589
TI  - Genes, environment and immunity in the development of rheumatoid arthritis.
AB  - The combined role of genes, environment and immunity in the development of
      rheumatoid arthritis (RA) has been the subject of recent investigations. New data
      support a gene-environment interaction between smoking and the MHC class II HLA
      DRB1 shared epitope (SE) genes in anti-citrulline antibody (anti-CP(+)) RA but
      not in anti-CP(-) disease. These data from genetic epidemiology, together with
      information on citrullination in the lungs of smokers, have prompted the
      formulation of a new etiological hypothesis for anti-CP(+) RA, suggesting that
      smoking in the context of HLA-DR SE might trigger immunity to citrulline-modified
      proteins and that this immunity, after several years, might cause arthritis.

PMID- 17010590
TI  - Mechanisms of the hygiene hypothesis--molecular and otherwise.
AB  - The hygiene hypothesis was initially formulated to explain the steep increase in
      the prevalence of allergies in Western societies observed over the past few
      decades. It proposes that the microbial environment interfaces with the innate
      immune system and modulates its ability to impart instructions to adaptive immune
      responses, particularly when such interactions occur in utero and/or in early
      life. Recent research on the molecular mechanisms of the hygiene hypothesis
      highlights the role of Toll-like receptor ligands in modulating allergic
      inflammation and the importance of bacterial products in directing the
      development of the host's immune system. Genetic analysis, by contrast, clearly
      shows that the response threshold of the immune system to environmental stimuli
      is controlled by natural genetic variation and gene-environment interactions,
      suggesting that the complex interplay between the organism and the environment
      might not be regulated by a single mechanism.

PMID- 17010591
TI  - Immune dysregulation in asthma.
AB  - Allergic diseases and asthma are caused by dysregulated Th2-biased immune
      responses to environmental allergens in genetically predisposed individuals. Over
      the past several years there has been much progress in understanding the
      mechanisms by which Th2 responses are generated and the pathogenic role of
      natural killer T cells in asthma. In addition, there has been much progress in
      understanding the mechanisms of tolerance to allergens, the role of natural and
      adaptive allergen-specific regulatory T cells, and the strategies to prevent or
      to reverse allergic disease and asthma. Impaired expansion of regulatory T cells
      is hypothesized to lead to the development of allergy and asthma, and treatment
      to induce allergen-specific regulatory T cells could provide curative therapies
      for these problems.

PMID- 17010592
TI  - The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation.
AB  - Autoimmune inflammatory responses and the diseases that develop as a consequence
      are now thought to be driven through a novel non-Th(1) pathway. IL-23, together
      with additional factors including TGF-beta1 and IL-6, collectively generate and
      sustain a distinct CD4(+) 'Th(17) inflammation effector' T-cell subset
      characterized by its production of inflammatory chemokines and cytokines,
      including IL-17. With this paradigm shift in understanding of autoimmune
      inflammation pathogenesis comes exciting opportunities to identify and to target
      therapeutically molecules within the IL-23/Th(17) axis that are key to disease
      development.

PMID- 17010593
TI  - Expression of genes involved in germination, conidiogenesis and pathogenesis in
      Metarhizium anisopliae using quantitative real-time RT-PCR.
AB  - Characterization of genes involved in germination, conidiogenesis and insect
      pathogenesis is an important step in identifying methods to increase the efficacy
      of Metarhizium anisopliae, a commercially important entomopathogenic fungus. Real
      time RT-PCR is a sensitive, reproducible and quantitative method to study gene
      expression. However, it requires reliable reference gene transcripts for
      normalization. In this study, six putative housekeeping genes (act, gpd, 18sRNA,
      tef, try and ubi) were investigated as reliable reference genes. Transcripts from
      tef, gpd and try were found to be the most suitable reference genes for real-time
      RT-PCR analysis of genes expressed during germination, conidiogenesis and
      pathogenesis. Using these as reference genes, the relative expression levels of a
      virulence gene, a subtilisin-like protease (pr1), a regulator of G protein
      signaling gene involved in conidiogenesis (cag8), the nitrogen response regulator
      gene (nrr1), and a hydrophobin gene (ssga) were studied. None of these
      transcripts could be detected in the early stages of insect pathogenesis. The
      nitrogen response regulator, nrr1, was consistently expressed during all
      developmental stages. Expression levels of cag8 increased significantly in the
      later stages of conidiogenesis on insect cadavers. The expression level of ssga
      during conidiogenesis was significantly higher than that in mycelia during
      vegetative growth in nutrient rich media. The pr1 gene was expressed during
      fungal conidiation on the insect cadaver. This study acts as a foundation for
      investigating the transcriptional levels of genes expressed during germination,
      conidiogenesis and pathogenesis of M. anisopliae using real-time RT-PCR.

PMID- 17010594
TI  - Detection and quantification of Erysiphe necator DNA in wine grapes and resultant
      must and juice.
AB  - Powdery mildew of grapevines is difficult to assess visually at the weighbridge,
      particularly in large consignments of machine-harvested fruit. To facilitate
      accurate methods for the detection and quantification of the disease in grape
      samples obtained from both the vineyard and winery, we developed a DNA probe for
      the pathogen Erysiphe necator. The E. necator-specific 450 bp DNA fragment pEnA1,
      targets highly repetitive sequences and was isolated from a partial genomic
      library. In screening for species specificity, clone pEnA1 was used in slot-blot
      hybridization and detected E. necator DNA from grapes and resultant must and
      juice, but not from clarified juice and wine. The detection threshold was
      approximately 50 pg of E. necator DNA per 100 ng total DNA of grape sample and
      was equivalent to 1-5% of a grape bunch visually affected by powdery mildew.
      Disease severity, expressed as the percentage of surface area of a bunch with
      powdery mildew, and E. necator DNA content were highly correlated, r2=0.955,
      P<0.001. The DNA-based hybridization assay has the potential to predict the
      severity of powdery mildew in grape samples from the vineyard and in must and
      juice samples at the winery. The DNA sequence of clone pEnA1 was used to design
      species-specific primers, the results maintaining the same specificity patterns
      observed in the initial hybridization assays. The PCR-based assay was sensitive
      enough to detect approximately 1 pg DNA, being equivalent to 1 conidium per
      sample. This is the first report to date of the detection of all known phenetic
      groups of E. necator DNA and of the quantification of DNA from grape samples at
      the winery. Accurate information on the extent of powdery mildew contamination of
      grape lots would enable wineries to make more informed decisions about the use of
      fruit and must.

PMID- 17010595
TI  - Overexpression of manganese superoxide dismutase by N-acetylcysteine in hyperoxic
      lung injury.
AB  - BACKGROUND: Exposure of animals to hyperoxia causes lung injury, characterized by
      diffuse alveolar damage and exudation of plasma into the alveolar space. Reactive
      oxygen species (ROS) play an important role in the development of hyperoxic lung
      injury. Mitochondrial oxidative phosphorylation is one of the major sources of
      ROS. N-acetylcysteine (NAC) is a precursor of glutathione (GSH), which functions
      as an antioxidant by reducing hydrogen peroxide to water and alcohols. NAC has
      been shown to diminish lung injury in a large variety of animal models. AIM: We
      elucidated the mechanism underlying the protective effects of NAC in hyperoxia
      induced lung injury. METHODS: Male BALB/c mice were exposed to 98% oxygen for 72
      h. The mice inhaled NAC or saline twice a day from 72 h before oxygen exposure to
      the end of experiment. RESULTS: Inhaled NAC increased the GSH level in lung
      homogenate. NAC also attenuated cellular infiltrations in both bronchoalveolar
      lavage fluid (BALF) and lung tissue. The total protein level in BALF and the
      level of 8-isoprostane, a marker of lipid peroxidation, in lung homogenate were
      decreased by inhalation of NAC. Inhaled NAC induced the overexpression of Mn
      superoxide dismutase (MnSOD) mRNA and protein, but did not alter the expressions
      of other antioxidant enzymes, including CuZnSOD, extracellular SOD, and
      glutathione peroxydase 1. CONCLUSION: These findings suggest that the antioxidant
      properties of NAC in hyperoxic lung injury involve a decrease in mitochondrial
      ROS in association with the induction of MnSOD, in addition to its role as a
      precursor of GSH.

PMID- 17010596
TI  - Determining biodegradability of plastic materials under controlled and natural
      composting environments.
AB  - With the advent of recently promulgated Government regulations on plastics in
      Mauritius, a study was initiated to examine the biodegradability of two different
      types of plastic, namely Willow Ridge Plastics - PDQ-H additive (Plastic A) and
      Ecosafe Plastic - TDPA additive (Plastic B) under controlled and natural
      composting environments. The results obtained from the controlled composting
      environment showed that the cumulative carbon dioxide evolution for Plastic A was
      much higher than that for Plastic B. Plastic A therefore showed a higher level of
      biodegradation in terms of CO2 evolution than Plastic B. However, from the
      regression analysis, it was found that the level of CO2 varying with time fitted
      the sigmoid type curves with very high correlation coefficients (R2 values:
      0.9928, 0.9921 and 0.9816, for reference material, inoculum and Plastic A,
      respectively). The corresponding F-values obtained from the ANOVA analysis
      together with significance levels of p<0.05 indicated that the three treatments
      analysed in the biodegradability experiment were significant. The other
      experiment was undertaken to observe any physical change of Plastics A and B as
      compared to a reference plastic, namely, compostable plastic bag (Mater-Bi
      product-Plastic C), when exposed to a natural composting environment.
      Thermophilic temperatures were obtained for about 3-5 days of composting and the
      moisture content was in the range of 60-80% throughout the degradation process.
      It was observed that after 55 days of composting, Plastic C degraded completely
      while Plastic A and Plastic B did not undergo any significant degradation. It can
      be concluded that naturally based plastic made of starch would degrade completely
      in a time frame of 60 days, whereas plastics with biodegradable additive would
      require a longer time.

PMID- 17010597
TI  - Comparison of different collection systems for sorted household waste in Sweden.
AB  - Composition and quantity per person of municipal solid waste (MSW) have been
      analyzed in six municipalities in southern Sweden with similar socio-economic
      conditions but with different collection systems. Samples of residual waste have
      been sorted, classified and weighed in 21 categories during 26 analyses that took
      place from 1998-2004. Collection data of the total waste flow, including source
      sorted recycling materials, in the same area have been compiled and compared.
      Multivariate data analyses have been applied. Weight-based billing reduced
      delivered amounts of residual household waste by 50%, but it is unknown to what
      extent improper material paths had developed. With curbside collection more
      metal, plastic and paper packaging was separated and left to recycling. When
      separate collection of biodegradables was included in the curbside system, the
      overall sorting of dry recyclables increased. The large uncertainty associated
      with waste composition analyses makes it difficult to draw strong conclusions
      regarding the effects on specific recyclables or the changes in the composition
      of the residual waste.

PMID- 17010598
TI  - Detection and modelling of DNA hybridization by EIS measurements. Mention of a
      polythiophene matrix suitable for electrochemically controlled gene delivery.
AB  - A conducting polymer sensor for direct label-free DNA detection based on a
      polythiophene bearing an electroactive linker group is investigated. DNA
      hybridization is studied by electrochemical impedance spectroscopy (EIS) and
      quartz crystal microbalance (QCM) techniques. Modelling of DNA hybridization by
      EIS measurements exhibits the contribution of nucleic acid to a superficial p
      doping process. A 675-mer single-stranded DNA is produced using asymmetric PCR
      from a DNA sequence of a transposable element mariner and hybridized to the
      previously immobilized probe. Electrochemical stimulus leads to the release "on
      demand" of DNA fragments and the amount delivery permits to do PCR amplification.

PMID- 17010599
TI  - Electrochemical genosensors for biomedical applications based on gold
      nanoparticles.
AB  - Two gold nanoparticles-based genomagnetic sensors designs for detection of DNA
      hybridization are described. Both assays are based on a magnetically induced
      direct electrochemical detection of gold tags on magnetic graphite-epoxy
      composite electrodes. The first design is a two strands assay format that
      consists of the hybridization between a capture DNA strand which is linked with
      paramagnetic beads and another DNA strand related to BRCA1 breast cancer gene
      used as a target which is coupled with streptavidin-gold nanoparticles. The
      second genomagnetic sensor design is a sandwich assay format with more
      application possibilities. A cystic fibrosis related DNA strand is used as a
      target and sandwiched between two complementary DNA probes: the first one linked
      with paramagnetic beads and a second one modified with gold nanoparticles via
      biotin-streptavidin complexation reactions. The electrochemical detection of gold
      nanoparticles by differential pulse voltammetry was performed in both cases. The
      developed genomagnetic sensors provide a reliable discrimination against
      noncomplementary DNA as well against one and three-base mismatches. Optimization
      parameters affecting the hybridization and analytical performance of the
      developed genosensors are shown for genomagnetic assays of DNA sequences related
      with the breast cancer and cystic fibrosis genes.

PMID- 17010600
TI  - Focusing on comparative ape population genetics in the post-genomic age.
AB  - The initial human and chimpanzee genome sequences have been published, and
      additional primate genomes, including those of gorilla and orang-utan, are in
      progress. With these new resources, we can now address what makes our species
      unique, by focusing on the underlying genetic differences associated with
      phenotypes. Comparative primate population genomics, including studies of
      structural changes, mobile elements, gene expression and functional analyses,
      will shed light on how natural selection and population demography are involved
      in the processes that lead to differences among great apes. Historically, this
      research has focused on the human perspective; however, we will learn much about
      ourselves with a focus on genomic diversity in hominoids as a group.

PMID- 17010601
TI  - Androgen receptor and vitamin D receptor gene polymorphisms and prostate cancer
      risk.
AB  - We study the CAG repeat region in exon 1 of the androgen receptor (AR) and the
      TaqI polymorphism in exon 9 of the vitamin D receptor (VDR) and the association
      with prostate cancer. 137 incidentally discovered, histologically verified
      prostate cancers were analysed for CAG repeat length in AR and genotype at the
      TaqI site of the VDR. 124 control subjects were analysed to determine the CAG
      repeat length and TaqI genotype determined for 176 control subjects. An unpaired
      t-test shows that the mean CAG repeat length was significantly (p<0.001) shorter
      among cases (20.1 repeats) compared with controls (22.5 repeats). Dividing the
      prostate cohort and controls into tertiles (< or = 19, 20-22, > or = 23 repeats)
      shows that short repeats are significantly more common among cases (odds ratio
      (OR) 4.45, p=0.00003). Genotype frequencies for the TaqI polymorphism reveals no
      significant differences between cases and controls. We conclude that men with a
      short CAG repeat in the androgen receptor gene have an increased risk of
      developing prostate cancer.

PMID- 17010602
TI  - The effect of hyperbaric oxygen therapy on tumour growth in a mouse model of
      colorectal cancer liver metastases.
AB  - BACKGROUND AND AIMS: Hyperbaric oxygen (HBO) therapy involves the administration
      of 100% oxygen at high pressure. It has been used to treat a variety of
      conditions including non-healing wounds, carbon monoxide poisoning, and as an
      adjuvant to radiotherapy or chemotherapy. The effect of HBO alone on the growth
      of malignancy remains controversial. This study investigates the impact of HBO on
      tumour growth, kinetics and microcirculation of colorectal cancer liver
      metastases in an experimental model. METHODS: Male CBA mice were induced with
      colorectal liver metastases via an intrasplenic injection of a murine derived
      colorectal cell line. Tumours were examined using quantitative stereological
      analysis, histology and scanning electron microscopy of microvascular resin
      casts. The effect of HBO on tumour proliferation and apoptosis was quantified
      using immunohistochemistry. RESULTS: Daily exposure to HBO at 2.4 atm for 90 min
      had no effect on the volume of liver metastases. At day 13, HBO caused a
      significant reduction in tumour necrosis and proliferation compared to the non
      HBO group (p=0.002 and p=0.008, respectively). By day 25 however, no differences
      were observed (p>0.05). No differences in apoptosis or microvascular architecture
      were observed. CONCLUSION: HBO did not have a tumour stimulatory effect on
      colorectal liver metastases and may potentially be used safely in conjunction
      with other therapeutic treatment modalities.

PMID- 17010603
TI  - The mammary gland response to estradiol: monotonic at the cellular level, non
      monotonic at the tissue-level of organization?
AB  - The role of hormones in mammary gland development has been studied in detail
      using surgical and genetic models. These studies have indicated roles for
      estrogen in ductal elongation and terminal end bud formation. However, no
      comprehensive study has quantified how different doses of estrogen affect
      morphological parameters of mammary gland development. Additionally, comparisons
      between the estrogen-responsiveness of the mammary gland and uterus, the model
      organ for estrogen action are incomplete. In this study, immature mice were
      ovariectomized and implanted with osmotic pumps releasing one of eight doses of
      17beta-estradiol for 10 days. As expected from the classical uterotrophic assay,
      the uterus showed a monotonic dose-response curve for all measured endpoints. In
      contrast, the mammary gland showed a non-monotonic, inverted-U shaped response to
      estrogen with regard to morphometric parameters, and a monotonic response with
      regard to gene expression parameters. These results indicate that estrogen has
      opposing effects in mammary gland morphogenesis depending on estrogen dose, i.e.
      low to moderate doses induce terminal end bud formation and ductal elongation
      while higher doses inhibit these processes. This non-monotonic dose-response in
      the mammary gland may reflect complex interactions, where estrogen can act on
      multiple targets either as an agonist or antagonist.

PMID- 17010604
TI  - Structure-based de novo design, synthesis, and biological evaluation of the
      indole-based PPARgamma ligands (I).
AB  - MCSS and LeapFrog, two de novo drug design programs, were used for the novel
      indole-based PPARgamma ligands' study. The designed compounds were synthesized
      and tested for the PPARgamma protein binding activities in vitro. Out of the
      compounds that were synthesized, two molecules (compounds 14d and 7d) possessed
      potent PPARgamma protein binding activity close to rosiglitazone in vitro.

PMID- 17010605
TI  - Discovery and design of benzimidazolone based inhibitors of p38 MAP kinase.
AB  - A new class of benzimidazolone p38 MAP kinase inhibitors was discovered through
      high-throughput screening. X-ray crystallographic data of the lead molecule with
      p38 were used to design analogues with improved binding affinity and potency in a
      cell assay of LPS-induced TNFalpha production. Herein, we report the SAR of this
      new class of p38 inhibitors.

PMID- 17010606
TI  - Discovery and in vitro/in vivo studies of tetrazole derivatives as Kv1.5
      blockers.
AB  - A novel class of tetrazole-derived Kv1.5 blockers is disclosed. In in vitro
      studies, several compounds had IC(50)s ranging from 180 to 550 nM. In vivo
      studies indicated that compounds 2f and 2j increased right atrial ERP about 40%
      without affecting ventricular ERP.

PMID- 17010607
TI  - Xanthine mimetics as potent dipeptidyl peptidase IV inhibitors.
AB  - A series of xanthine mimetics containing 5,5 and 5,6 heterocycle fused imidazoles
      were synthesized as dipeptidyl peptidase IV inhibitors. Compound 7 is potent (h
      DPPIV K(i)=2nM) and exhibits excellent selectivity and no species specificity
      against rat and human enzymes. The X-ray structure confirms that the binding mode
      of 7 to rat DPPIV is similar to the parent xanthines.

PMID- 17010608
TI  - Structural correlation between lipophilicity and lipopolysaccharide-sequestering
      activity in spermine-sulfonamide analogs.
AB  - Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are outer-membrane
      constituents of Gram-negative bacteria, and play a key role in the pathogenesis
      of 'Septic Shock', a major cause of mortality in the critically ill patient. We
      had previously defined the pharmacophore necessary for small molecules to
      specifically bind and neutralize this complex carbohydrate. A series of aryl and
      aliphatic spermine-sulfonamide analogs were synthesized and tested in a series of
      binding and cell-based assays in order to probe the effect of lipophilicity on
      sequestration ability. A strong correlation was indeed found, supporting the
      hypothesis that endotoxin-neutralizing ability involves a lipophilic or membrane
      attachment event. The research discussed herein may be useful for the design of
      additional carbohydrate recognizing molecules and endotoxin-neutralizing drugs.

PMID- 17010609
TI  - Gene expression profiling of breast cancer patients treated with docetaxel,
      doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not
      topoisomerase II alpha and microtubule-associated protein tau, is highly
      predictive of tumor response.
AB  - Gene expression analysis in breast cancer patients undergoing neoadjuvant
      chemotherapy is an interesting tool for identification of gene signatures and new
      markers to predict tumor response. However, the detection of predictive markers
      strongly depends on the drugs used in the specific therapeutic setting. There is
      growing evidence that topoisomerase II-alpha (TOPO IIalpha) is a marker for
      anthracycline-, and microtubule-associated protein tau (MAPT) for taxane
      sensitivity. HER-2 has been described as a marker of both anthracycline and
      taxane sensitivity. We performed gene expression profiling of 50 patients within
      the GEPARTRIO study, an anthracycline and taxane neoadjuvant chemotherapy trial.
      Here we investigate the predictive value of TOPO IIalpha, MAPT and HER-2 mRNA
      expression for pathological complete response (pCR) in this setting.
      Interestingly, HER-2 gene expression was strongly predictive of pCR (P=0.017) as
      well as overall response (P=0.037) and clinical complete response (cCR, P=0.050).
      In contrast, for both TOPO IIalpha and MAPT no correlation with pCR was observed
      in our sample group.

PMID- 17010610
TI  - The characteristics of gait in Charcot-Marie-Tooth disease types I and II.
AB  - Certain typical gait characteristics such as foot-drop and foot supination are
      well described in Charcot-Marie-Tooth disease. These are directly related to the
      primary disease and due to the weakness of ankle dorsiflexors and everters
      characteristic of this hereditary neuropathy. We analysed 16 subjects aged 8-52
      years old (11 with type I, 5 with type II Charcot-Marie-Tooth disease) using
      three-dimensional gait analysis and identified kinematic features previously
      unreported. These patients showed a combination of tight tendo achillei, foot
      drop, failure of plantar flexion and increased foot supination, but also
      presented with excessive internal rotation of the knee and/or tibia, knee
      hyperextension in stance, excessive external rotation at the hips and decreased
      hip adduction in stance (typical of a broad based gait). These proximal features
      could have been an adaptation to or consequence of the disrupted ankle and foot
      biomechanics, however a direct relation to the neuropathy is also possible since
      sub-normal muscle power was observed at the proximal levels in most subjects on
      both manual testing and kinetic analysis. Gait analysis is a useful tool in
      defining the characteristic gait of patients with Charcot-Marie-Tooth disease.

PMID- 17010611
TI  - Internal rotation gait in spastic diplegia--critical considerations for the
      femoral derotation osteotomy.
AB  - The purpose of this study was to assess under- and overcorrection following
      femoral derotation osteotomy (FDO) in spastic diplegic children with functionally
      compromising internally rotated gait, especially with respect to asymmetry. A
      total of 30 children with spastic diplegia and internally rotated gait underwent
      multilevel surgery including FDO and were assessed pre- and 1 year
      postoperatively by clinical examination and instrumented gait analysis. The
      amount of derotation was determined intra-operatively based on the neutral
      midpoint between passive internal and external hip rotation and was controlled
      with K-wires. Sixteen patients showed an asymmetry in mean hip rotation in stance
      of more than 10 degrees preoperatively. Accordingly, all legs were classified as
      the more or the less involved side. Improvement parameters were established for
      the evaluation of over- and undercorrection. For the clinical midpoint, no
      significant difference in change and improvement was found between the sides. The
      mean hip rotation in stance improved significantly in the more involved side with
      few incidences of mal-correction (13%). The less involved side, however, got
      worse due to a high occurrence of over- and undercorrections (59%). Hence the
      clinical midpoint as indication criterion does not give sufficient information
      about the functional alignment of the distal femur during gait, especially in
      legs with mild involvement. The study underlines the importance of gait analysis
      for indication in addition to the clinical midpoint. Taking into account the
      precision of gait analysis data and derotation amount, we suggest FDO to be
      carried out if the mean internal hip rotation in stance exceeds 15 degrees .

PMID- 17010612
TI  - Evaluation of instrumented shoes for ambulatory assessment of ground reaction
      forces.
AB  - Currently, force plates or pressure sensitive insoles are the standard tools to
      measure ground reaction forces and centre of pressure data during human gait.
      Force plates, however, impose constraints on foot placement, and the available
      pressure sensitive insoles measure only one component of force. In this study,
      shoes instrumented with two force transducers measuring forces and moments in
      three dimensions were evaluated. Technical performance was assessed by comparing
      force measurement and centre of pressure reconstructions of the instrumented
      shoes against a force plate. The effect of the instrumented shoes on gait was
      investigated using an optical tracking system and a force plate. Instrumented
      shoes were compared against normal shoes and weighted shoes. The ground reaction
      force measured with force plate and instrumented shoes differed by 2.2+/-0.1% in
      magnitude and by 3.4+/-1.3 degrees in direction. The horizontal components
      differed by 9.9+/-3.8% in magnitude and 26.9+/-10.0 degrees in direction. Centre
      of pressure location differed by 13.7+/-2.4mm between measurement systems. A
      MANOVA repeated measures analysis on data of seven subjects, revealed significant
      differences in gait pattern between shoe types (p</=0.05). A subsequent
      univariate analysis showed significant differences only in maximum ground
      reaction force but these could not be attributed to specific shoe types by pair
      wise comparison. This study indicates that shoes instrumented with force
      transducers can be a valuable alternative to current measurement systems if
      accurate sensing of position and orientation of the force transducers is
      improved. They are applicable in ambulatory settings and suitable for inverse
      dynamics analysis.

PMID- 17010613
TI  - Nonsense-mediated mRNA decay: Target genes and functional diversification of
      effectors.
AB  - Recent genome-wide identification of nonsense-mediated mRNA decay (NMD) targets
      in yeast, fruitfly and human cells has provided insight into the biological
      functions and evolution of this mRNA quality control mechanism, revealing that
      NMD post-transcriptionally regulates an important fraction of the transcriptome.
      NMD targets are associated with a broad range of biological processes, but most
      of these targets are not encoded by orthologous genes across different species.
      Yeast and fruitfly NMD effectors regulate common targets in concert, but parallel
      pathways have evolved in humans, whereby NMD effectors have acquired additional
      functions. Thus, the phenotypic differences observed across species after
      inhibition of NMD are driven not only by the functional diversification of NMD
      effectors but also by changes in the repertoire of regulated genes.

PMID- 17010614
TI  - RAMPs: The past, present and future.
AB  - The discovery of receptor-activity-modifying proteins (RAMPs) as accessory
      proteins required for the appropriate localization and function of certain G
      protein coupled receptors (GPCRs) produced a paradigm shift in our understanding
      of GPCR regulation. Three RAMPs have now been demonstrated to be crucial for
      various aspects of the life cycle of calcitonin-like receptor (CLR) including
      endoplasmic reticulum-to-Golgi translocation, internalization and recycling.
      Although the RAMP-CLR interaction was the first to be identified, other GPCRs
      belonging to both the class B and C families of GPCRs also seem to be regulated
      by RAMPs. The recent advances in our knowledge of the cellular and biochemical
      regulation of RAMPs and how they in turn regulate the life cycle of GPCRs could
      lead to therapeutic advances in several diseases.

PMID- 17010615
TI  - Probing the physicochemical and structural requirements for glycogen synthase
      kinase-3alpha inhibition: 2D-QSAR for 3-anilino-4-phenylmaleimides.
AB  - Glycogen synthase kinase-3alpha (GSK-3alpha) was recently found to be an
      attractive target for the treatment of Alzheimer's disease due to its dual action
      in the formation of both amyloid plaques and neurofibrillary tangles. It is also
      a viable target for many other diseases, such as type 2 diabetes. Reported herein
      is a 2D-QSAR exploration of the physicochemical (hydrophobic, electronic, and
      steric) and structural requirements among 3-anilino-4-phenylmaleimides toward GSK
      3alpha binding. Using Fujita-Ban and Hansch QSAR analysis, electronic and steric
      interactions at the 4-phenyl ring and hydrophobic interactions at the 3-anilino
      ring are shown to be crucial. Analysis of the 4-phenyl ring of these compounds
      using common aromatic substituent constants showed electron-withdrawing and bulky
      ortho substituents as imperative for GSK-3alpha inhibition.

PMID- 17010616
TI  - The synthesis and the in vitro cytotoxicity studies of bisnaphthalimidopropyl
      polyamine derivatives against colon cancer cells and parasite Leishmania
      infantum.
AB  - Bisnaphthalimidopropyl derivatives (BNIPSpd, BNIPDaoct, BNIPDanon, BNIPDadec,
      BNIPDpta and BNIPDeta) were synthesised in yields ranging from 50% to 70% and
      their cytotoxicity against colon cancer cells (Caco-2) and the parasite
      Leishmania infantum determined using the MTT assay. Cytotoxicity within Caco-2
      cells was manifested with IC(50) values between 0.3 and 22 microM. Compounds with
      the central longer alkyl chains exhibited the highest cytotoxicity. Against L.
      infantum, IC(50) values were encompassed within a narrower concentration range of
      0.47-1.54 microM. In the parasites, the presence of nitrogen in the central chain
      and the length of the central alkyl chains did not especially enhance
      cytotoxicity. This may be due to the way these compounds are transported in the
      cells.

PMID- 17010617
TI  - Synthesis and antitubercular activity of substituted phenylmethyl- and
      pyridylmethyl amines.
AB  - A total of 42 benzyl- and pyridylmethyl amines were synthesized either by
      reductive amination of aromatic/heteroaromatic aldehydes with amines or by
      conjugate addition of amines to the cinnamates followed by reduction of the ester
      group with lithium aluminium hydride to the respective propanolamines. All the
      synthesized compounds were evaluated against both avirulent and virulent strains
      of Mycobacterium tuberculosis. Many of the compounds exhibited MIC as low as
      1.56microg/mL. Few of potent compounds were also evaluated against clinical
      isolates of MDR TB and found to be active at one or other concentrations with MIC
      as low as 3.12microg/mL.

PMID- 17010618
TI  - Discovery of novel, highly potent and selective beta-hairpin mimetic CXCR4
      inhibitors with excellent anti-HIV activity and pharmacokinetic profiles.
AB  - Novel highly potent CXCR4 inhibitors with good pharmacokinetic properties were
      designed and optimized starting from the naturally occurring beta-hairpin peptide
      polyphemusin II. The design involved incorporating important residues from
      polyphemusin II into a macrocyclic template-bound beta-hairpin mimetic. Using a
      parallel synthesis approach, the potency and ADME properties of the mimetics were
      optimized in iterative cycles, resulting in the CXCR4 inhibitors POL2438 and
      POL3026. The inhibitory potencies of these compounds were confirmed in a series
      of HIV-1 invasion assays in vitro. POL3026 showed excellent plasma stability,
      high selectivity for CXCR4, favorable pharmacokinetic properties in the dog, and
      thus has the potential to become a therapeutic compound for application in the
      treatment of HIV infections (as an entry inhibitor), cancer (for angiogenesis
      suppression and inhibition of metastasis), inflammation, and in stem cell
      transplant therapy.

PMID- 17010619
TI  - An RNA polymerase inhibitor, cyclothiazomycin B1, and its isomer.
AB  - Novel cyclic thiopeptides, cyclothiazomycins B1 (1) and B2 (2), were isolated
      from Streptomyces sp. A307 as potent hyphal swelling inducing substances. They
      are stable in the solid state but slowly isomerize with one another in solution.
      Degradation experiments and spectroscopic analyses disclosed that they comprise
      unique tricyclic structures each containing a dehydroalanine, and two
      dehydrohomoalanine residues, along with three thiazolines, three thiazoles, and a
      trisubstituted pyridine. Cyclothiazomycin B1 (1) is expected to be a powerful
      tool for DNA-RNA transcription studies, because this cyclopeptide inhibits DNA
      dependent RNA synthesis by bacteriophage RNA polymerases.

PMID- 17010620
TI  - Synthesis of amino acid derived seven-membered lactams by RCM and their
      evaluation against HIV protease.
AB  - A versatile synthesis of hydroxylated and epoxy 1-azepin 2-ones substituted at
      N1, C-3 and C-4 or C-7 has been developed. The sequence involves ring-closing
      metathesis of an amino acid derived diene amide, followed by either epoxidation
      or dihydroxylation, of the resulting alkene. Assay of the product epoxides (10,
      18, 25) and diols (9a, 17, 24) against HIV protease reveals micromolar
      inhibition.

PMID- 17010621
TI  - Synthesis, enzymatic activity, and X-ray crystallography of an unusual class of
      amino acids.
AB  - The synthesis of two novel amino acids, nitrogen analogues of the naturally
      occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt
      are described, along with the crystal structure of one of these analogues in the
      active site of Drosophila melanogaster Golgi mannosidase II (dGMII). Salacinol, a
      naturally occurring sulfonium ion, is one of the active principals in the aqueous
      extracts of Salacia reticulata that are traditionally used in Sri Lanka and India
      for the treatment of diabetes. The synthetic strategy relies on the nucleophilic
      attack of 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino l- or d-arabinitol at the
      least hindered carbon of 5,6-anhydro-2,3-di-O-benzyl-l-ascorbic acid to yield
      coupled adducts. Deprotection, stereoselective catalytic reduction, and
      hydrolysis of the coupled products give the target compounds. The compound
      derived from d-arabinitol inhibits dGMII, one of the critical enzymes in the
      glycoprotein processing pathway, with an IC(50) of 0.3mM. Inhibition of GMII has
      been identified as a target for control of metastatic cancer. An X-ray crystal
      structure of the complex of this compound with dGMII provides insight into the
      requirements for an effective inhibitor. The same compound inhibits recombinant
      human maltase glucoamylase, one of the key intestinal enzymes involved in the
      breakdown of glucose oligosaccharides in the small intestine, with a K(i) value
      of 21microM.

PMID- 17010622
TI  - Effect of melanin on netilmicin-induced inhibition of collagen biosynthesis in
      human skin fibroblasts.
AB  - It is known that various drugs form complexes with melanins and that melanins are
      abundant constituents of the inner ear. In this study, we determined whether the
      aminoglycoside antibiotic, netilmicin, interacts with melanin and how this
      process affects collagen biosynthesis in cultured human skin fibroblasts. The
      obtained results indicate that netilmicin forms stable complexes with melanin
      characterized by the association constants K(1) approximately 10(6)M(-1) and K(2)
      approximately 10(3)M(-1). We have suggested that prolidase, an enzyme involved in
      collagen metabolism, may be one of the targets for aminoglycoside-induced
      inhibition of collagen biosynthesis. We found that netilmicin strongly induced
      inhibition of prolidase activity (IC(50)<5microM) and collagen biosynthesis
      (IC(50) approximately 10microM). At 10microM concentration of netilmicin,
      prolidase activity in human skin fibroblasts was inhibited by about 80% and DNA
      biosynthesis-only by about 25%. Melanin at 100microg/mL produced about 30%
      inhibition of collagen biosynthesis and about 30% inhibition of prolidase
      activity in cultured fibroblasts. However, the addition of melanin (100microg/mL)
      to netilmicin-treated cells (10microM) restored the prolidase activity in
      fibroblasts to almost 100% of control values and partially reversed the
      inhibitory action of the drug on collagen and DNA biosynthesis. The data suggest
      that the ability of netilmicin to form stable complexes with melanin may prevent
      its toxicity on prolidase activity and collagen biosynthesis.

PMID- 17010623
TI  - A platform for designing HIV integrase inhibitors. Part 1: 2-hydroxy-3-heteroaryl
      acrylic acid derivatives as novel HIV integrase inhibitor and modeling of
      hydrophilic and hydrophobic pharmacophores.
AB  - We present a novel series of HIV integrase inhibitors, showing IC(50)s ranging
      from 0.01 to over 370microM in an enzymatic assay. Furthermore, pharmacophore
      modeling study for the inhibitors was carried out to elucidate the structure
      activity relationships. Finally, we found a 3D-pharmacophore model, which is
      composed of a hydrophilic and a hydrophobic domain, providing valuable
      information for designing other novel types of integrase inhibitors.

PMID- 17010624
TI  - Synthesis of some substituted pyrazinopyridoindoles and 3D QSAR studies along
      with related compounds: piperazines, piperidines, pyrazinoisoquinolines, and
      diphenhydramine, and its semi-rigid analogs as antihistamines (H1).
AB  - 3D QSAR studies on the title compounds led to the development of a model with
      three biophoric sites and six secondary sites viz. H-acceptor (ACC), H-donor
      (DON), heteroatom (presence), hydrophobic (hydrophobicity), steric
      (refractivity), and a ring (presence) along with total hydrophobicity and total
      refractivity as global properties. The model predicted the test set of compounds
      reasonably well. Three of the five newly synthesized 2-substituted
      octahydropyrazinopyridoindoles have shown potent antihistaminic H(1) activity
      with less toxicity and sedation potential.

PMID- 17010625
TI  - Novel non-classical C9-methyl-5-substituted-2,4-diaminopyrrolo[2,3-d]pyrimidines
      as potential inhibitors of dihydrofolate reductase and as anti-opportunistic
      agents.
AB  - Six novel C9-methyl-5-substituted-2,4-diaminopyrrolo[2,3-d]pyrimidines 18-23 were
      synthesized as potential inhibitors of dihydrofolate reductase (DHFR) and as anti
      opportunistic agents. These compounds represent the only examples of 9-methyl
      substitution in the carbon-carbon bridge of 2,4-diaminopyrrolo[2,3-d]pyrimidines.
      The analogs 18-23 were synthesized in a concise eight-step procedure starting
      from the appropriate commercially available aromatic methyl ketones. The key step
      involved a Michael addition reaction of 2,4,6-triaminopyrimidine to the
      appropriate 1-nitroalkene, followed by ring closure of the nitro adducts via a
      Nef reaction. The compounds were evaluated as inhibitors of DHFR from
      Pneumocystis carinii (pc), Toxoplasma gondii (tg), Mycobacterium avium (ma) and
      rat liver (rl). The biological result indicated that some of these analogs are
      potent inhibitors of DHFR and some have selectivity for pathogen DHFR. Compound
      23 was a two digit nanomolar inhibitor of tgDHFR with 9.6-fold selectivity for
      tgDHFR.

PMID- 17010626
TI  - Effect of mating delay on the ovary of Melipona quadrifasciata anthidioides
      (Hymenoptera: Apidae) queens.
AB  - The effect of mating delay on the ovary structure of virgin queens of Melipona
      quadrifasciata anthidioides (Hymenoptera: Apidae) was investigated. Virgin queens
      15, 20, 25 and 30 days old were dissected to analyze their degree of ovary
      degeneration. To verify whether the degeneration would cause permanent sterility,
      virgin queens of the same ages (15, 20, 25 and 30 days) were mated and
      accompanied for at least 14 days to verify whether there was physogastry and then
      dissected. The ovaries were analyzed by histology, histochemical tests and TUNEL
      to verify programmed cell death. The results showed that mating delay interrupted
      oogenesis preventing vitellogenesis. Mating delay results in ovary degeneration
      which increased with queen age. However, even when there was ovariole
      degeneration, 25-day-old virgin queens after mating presented normal ovariole
      activation.

PMID- 17010627
TI  - A comparative study on the characteristics of radioactivities and negative air
      ions originating from the minerals in some radon hot springs.
AB  - To elucidate the characteristics of some radon hot springs, we simulated a hot
      spring by soaking the rocks for the radon therapy in water and measured the
      concentrations of radon and negative air ions in various conditions. In the
      results, the individual rock structure could contribute to radon leaching because
      the radon leaching rates were independent of the grain sizes. More negative air
      ions were generated by the wet rocks than by the dry rocks.

PMID- 17010628
TI  - Development of acetylated HDD kit for preparation of 188Re-HDD/lipiodol.
AB  - A lipiodol solution of (188)Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10
      decanedithiol ((188)Re-HDD/lipiodol) is in clinical study for liver cancer
      therapy. However, formulation of it is difficult due to highly active and
      unstable sulfhydryl groups. We produced new kits using diacetylated HDD (AHDD),
      in which sulfhydryl groups are protected. We found that AHDD kit can replace HDD
      kit due to an increased stability for formulation, the better radiolabeling
      efficiency (78%) and the equivalent biodistribution pattern in mice.

PMID- 17010629
TI  - Erythropoietin protects sensory axons against paclitaxel-induced distal
      degeneration.
AB  - Paclitaxel causes a sensory polyneuropathy with characteristic features of distal
      axonal degeneration. Although the exact mechanisms underlying distal axonal
      degeneration are unknown, paclitaxel-induced axonal degeneration has been shown
      to be associated with an increase in detyrosinated tubulin. Here we show that
      recombinant human erythropoietin prevents axonal degeneration in sensory neurons
      in vitro and this effect is associated with downregulation of detyrosinated
      tubulin. Furthermore, in an animal model of paclitaxel-induced distal sensory
      polyneuropathy, recombinant human erythropoietin protects against distal axonal
      degeneration. These findings suggest that recombinant human erythropoietin may be
      useful as a therapy to prevent paclitaxel-induced sensory polyneuropathy in
      patients undergoing chemotherapy.

PMID- 17010630
TI  - Pomegranate juice decreases amyloid load and improves behavior in a mouse model
      of Alzheimer's disease.
AB  - Although there are no proven ways to delay onset or slow progression of
      Alzheimer's disease (AD), studies suggest that diet can affect risk. Pomegranates
      contain very high levels of antioxidant polyphenolic substances as compared to
      other fruits and vegetables. Polyphenols have been shown to be neuroprotective in
      different model systems. We asked whether dietary supplementation with
      pomegranate juice (PJ) would influence behavior and AD-like pathology in a
      transgenic mouse model. Transgenic mice (APP(sw)/Tg2576) received either PJ or
      sugar water control from 6 to 12.5 months of age. PJ-treated mice learned water
      maze tasks more quickly and swam faster than controls. Mice treated with PJ had
      significantly less (approximately 50%) accumulation of soluble Abeta42 and
      amyloid deposition in the hippocampus as compared to control mice. These results
      suggest that further studies to validate and determine the mechanism of these
      effects, as well as whether substances in PJ may be useful in AD, should be
      considered.

PMID- 17010631
TI  - Overactivity of exercise-sensitive cation channels and their impaired modulation
      by IGF-1 in mdx native muscle fibers: beneficial effect of pentoxifylline.
AB  - Cell-attached patch-clamp recordings on native striated myofibers from adult
      dystrophic mdx mice revealed a higher occurrence and open probability compared to
      non-dystrophic wild-type myofibers of a 30 pS voltage-insensitive Ca2+-permeable
      channel, inhibited by Gd3+, streptomycin and ruthenium red. Myofibers from in
      vivo exercised animals had higher channel occurrence and/or open probability.
      Insulin-like growth factor 1 (3.3 nM) induced and/or enhanced channel activity,
      via PI3 kinase, in wild-type but not in mdx myofibers. Interestingly, in both
      genotypes the current was silenced by db-cAMP or pentoxifylline, a
      phosphodiesterase inhibitor. The channel activity/occurrence in pentoxifylline
      treated exercised mdx (50 mg/kg/day i.p. for 4-8 weeks) overlapped that of
      exercised wild-type mice. Thus, a growth factor-sensitive current, likely due to
      a TRP channel, is activated in vivo by exercise in native striated fibers; its
      deregulation in the absence of dystrophin may contribute to Ca2+ homeostasis
      alteration. The possibility to pharmacologically counteract abnormal channel
      activity discloses important therapeutic application.

PMID- 17010632
TI  - Cloning of a cDNA encoding the Saussurea medusa chalcone isomerase and its
      expression in transgenic tobacco.
AB  - Chalcone isomerase (CHI; EC 5.5.1.6) is a key enzyme in the flavonoid
      biosynthesis pathway. We isolated a CHI gene (SmCHI) from a cDNA library derived
      from Saussurea medusa (Asteraceae) cell cultures. The cDNA and genomic sequences
      of SmCHI are the same; in other words, this gene is intronless. The coding region
      of the gene is 699 bp long, and its deduced protein consists of 232 amino acids
      with a predicted molecular mass of 24 kDa and a pI of 4.7. The deduced amino acid
      sequence of SmCHI shares 79.3% identity with CHI from Callistephus chinensis, a
      familial relative to S. medusa; this homology is higher than those with CHI's
      from any other plant species. A functional bioassay for SmCHI was performed by
      transforming Nicotiana tabacum plants in the sense or antisense orientation under
      the regulation of the cauliflower mosaic virus (CaMV) 35S promoter. Transgenic
      tobacco plants overexpressing sense SmCHI produced up to fivefold total
      flavonoids over wild-type tobacco plants, mainly due to an enhanced accumulation
      of rutin. Transgenic tobacco plants with antisense SmCHI accumulated smaller
      amounts of flavonoids; this is apparently brought about by suppressed expression
      of the endogenous CHI gene. CHI activities also positively correlated with the
      amounts of total flavonoids accumulated in the transgenic plants. It is concluded
      that overexpression of SmCHI can be used as a useful approach to increase
      flavonoid production in transgenic plants.

PMID- 17010633
TI  - Normothermic cardiopulmonary bypass and myocardial cardioplegic protection for
      neonatal arterial switch operation.
AB  - OBJECTIVE: Hypothermic cardiopulmonary bypass (CPB) associated with cold
      myocardial protection is commonly used to perform neonatal cardiac surgery.
      Hypothermia is usually chosen to preserve the brain in case of failure of oxygen
      delivery whatever it may result from. Nowadays, there is a growing number of
      evidence demonstrating that hypothermia induces deleterious effects, which may
      culminate in organ dysfunctions. In 2001, we started a protocol where the heart
      and the body were no longer cooled, in all the procedures, including the arterial
      switch operation (ASO), except those with aortic arch reconstruction. METHODS:
      Because data on the neonatal arterial switch operation were prospectively
      gathered in our unit (and included fine biochemical analysis of myocardial
      damage), we have compared two consecutive populations of arterial switch
      operation to sort out the impact of normothermic CPB and normothermic
      cardioplegia. RESULTS: The results show that warm cardiopulmonary bypass
      associated with warm cardioplegia is feasible for ASO, and that most of the
      operative data are similar to hypothermic bypass, none are worse. Among the
      postoperative data, the cardiac troponin I (cTnI) time course showed
      significantly lower values in the normothermic group after 24 h (4.46 ng ml(-1)
      vs 6.17 ng ml(-1) (p = 0.027)), time to extubation is improved (32+/-26 h vs 70+/
      69 h (p = 0.02)) and there is a trend to reduce the ICU length of stay (3.5+/-1.5
      days vs 5.6+/-3.9 days (p = 0.08)), and consequently the cost of surgery.
      CONCLUSION: Normothermic cardiopulmonary bypass is feasible for ASO and seems to
      allow a faster recovery time.

PMID- 17010634
TI  - Low birth weight or diagnosis, which is a higher risk?--A meta-analysis of
      observational studies.
AB  - Published experience with surgical treatment of newborns with low birth weight
      and congenital heart disease is circumscribed to isolated single case reports and
      a limited number of case-series. To better assess the risks of early surgical
      treatment and its relationship to weight and diagnosis we performed a meta
      analysis of observational studies, limited to those from which data on individual
      patients could be extrapolated. A search on the subject in peer-reviewed journals
      published between 1993 and 2004 limited the number of studies, according to our
      restrictive criteria, to six articles. Our own series of 37 patients was added to
      the body of data collected in the meta-analyses. Data on 356 individually
      identified patients was extracted from the articles. Median weight was 2.05 kg
      (range 1.1-2.5) and median gestational age was 34.2 weeks (range 26-42). Overall
      surgical survival was 83.9% but survival was higher when a full repair was done
      (86.1%). According to our analysis, diagnosis was the most significant predictor
      of mortality (p = 0.001). Other important predictors were the presence of a
      surgical complication (p = 0.01), palliative surgery (p = 0.03) and the need for
      reoperation during the same admission (p = 0.03). We concluded that similarly to
      larger newborns, diagnosis in this group of patients is the most important
      predictor of mortality. Independently of patient's weight a full anatomic and
      physiologic repair is justified in most cases.

PMID- 17010635
TI  - Role of physiological state 'normothermia' in internal thoracic artery spasm
      after harvesting.
AB  - OBJECTIVE: Vasospasm is often faced after the operative preparation of internal
      thoracic artery. Different vasodilating pharmacological agents are being used to
      eliminate this problem. During the preparation of internal thoracic artery,
      normal, local, and systemic temperatures are lost. We aimed to find out the
      effect of this decrease in temperature on the free flow of internal thoracic
      artery. METHODS: We investigated the effects of normal saline solution at 20
      degrees C (group I), papaverine at 20 degrees C (group II) and normal saline
      solution at 37 degrees C (group III). Each group contained 20 patients undergoing
      coronary bypass. Free flow of the left internal thoracic artery was measured
      after mobilization. After approximately 18 min the graft had been sprayed with
      one of the agents, and the second free flow was measured (t-interval was 18.2+/
      2.1 for group I, 18.3+/-1.8 for group II, and 17.5+/-1.9 for group III). RESULTS:
      Normal saline solution at 20 degrees C did not cause a significant change.
      Topical papaverine at 20 degrees C increased the flow from 42.1+/-10.7 ml/min to
      77.5+/-17.9 ml/min (p < 0.0001). A significant increase also occurred with normal
      saline solution at 37 degrees C from 41+/-11.9 ml/min to 75.3+/-18.9 ml/min (p <
      0.0001). CONCLUSIONS: After harvesting the graft, regaining physiological
      normothermic state is enough for vasodilatation. Even using one of the most
      potent vasodilating agent papaverine at 20 degrees C is not superior to
      normothermia.

PMID- 17010636
TI  - 'Because we can, should we ...?'.

PMID- 17010637
TI  - Mammalian sexual differentiation: lessons from the spotted hyena.
AB  - Female spotted hyenas (Crocuta crocuta) are the only female mammals that lack an
      external vaginal opening. Mating and birth take place through a urogenital canal
      that exits at the tip of a hypertrophied clitoris. This 'masculine' phenotype
      spurred a search for an alternate source of fetal androgens. Although
      androstenedione from the maternal ovary is readily metabolized to testosterone by
      the hyena placenta, formation of the penile clitoris and scrotum appear to be
      largely androgen independent. However, secretions from the fetal testes underlie
      sex differences in the genitalia and central nervous system that are essential
      for male reproduction. Naturally circulating androgens, acting prenatally, reduce
      reproductive success in adult female spotted hyenas. Effects on aggression and
      dominance might offset these reproductive 'costs' of female androgenization in
      utero.

PMID- 17010638
TI  - Attenuation of leptin and insulin signaling by SOCS proteins.
AB  - Leptin and insulin are key hormones involved in the regulation of energy balance
      and glucose homeostasis. Development of resistance to the action of these
      hormones, which can occur with age, obesity and inflammation, appears to have a
      prime role in the pathogenesis of obesity and type 2 diabetes. Specific members
      of the suppressor of cytokine signaling (SOCS) family of proteins are now thought
      to have a role in the development of leptin and insulin resistance owing to their
      ability to inhibit leptin and insulin signaling pathways. In the case of leptin,
      current evidence suggests that SOCS3 appears to be of particular importance in
      the development of leptin resistance, whereas the ability to diminish insulin
      action has been described for several SOCS proteins (SOCS1, SOCS3, SOCS6 and
      SOCS7).

PMID- 17010639
TI  - Development of leptin antagonists and their potential use in experimental biology
      and medicine.
AB  - Leptin is a pleotropic hormone that acts both centrally and peripherally. Whereas
      leptin exhibits positive effects on several physiological functions, such as
      regulation of energy metabolism, reproductive function and immune responses,
      negative actions, such as enhancement of undesired immune responses in autoimmune
      diseases, tumorigenesis, elevated blood pressure and cardiovascular pathologies,
      have also been documented. The recent development of leptin muteins with
      antagonistic properties and other proteins that block leptin activity opens up
      new possibilities for their use in research and, eventually, therapy.

PMID- 17010640
TI  - Electrophysiological effects of brompheniramine on cardiac ion channels and
      action potential.
AB  - Some antihistamines (mainly terfenadine and astemizole) have been demonstrated to
      cause QT interval prolongation and, in some cases, torsade-de-pointes. We
      investigated the cardiac electrophysiological effects of brompheniramine, a
      conventional antihistamine. Brompheniramine was reported to prolong QT interval
      in isolated hearts. To evaluate the electrophysiological effects of
      brompheniramine, we used whole-cell patch clamp techniques in human ether-a-go-go
      related gene (hERG)-stably transfected CHO cells, the SCN5A sodium channel
      transiently transfected CHO cells, and rat myocytes and conventional
      microelectrode recording techniques in isolated guinea pig papillary muscles. As
      for the I(hERG), the IC(50) value of brompheniramine was found to be 0.90+/
      0.14microM with a Hill coefficient (n(H)) of 1.75+/-0.42. Action potential
      duration at 90% repolarization (APD(90)) was slightly prolonged by
      brompheniramine at 10 and 100microM, but APD(50) was shortened by 100microM.
      Moreover, despite the potent hERG current block, reductions of the V(max) and
      total amplitude of action potential were observed at high concentrations of
      brompheniramine. The change in action potential parameters and poor correlations
      between hERG and APD assay indicated additional effects of brompheniramine on non
      hERG channels. In agreement with this hypothesis, the inhibition of I(Na) (IC(50)
      values: 21.26+/-2.52microM) and I(Ca) (IC(50) values: 16.12+/-9.43microM) by
      brompheniramine was observed. The results of this study suggest that
      brompheniramine may possess classes III, Ib and IV properties, especially at high
      concentrations and that additional studies on non-hERG channels will be necessary
      to elucidate the complex electrophysiological effects of brompheniramine on the
      heart.

PMID- 17010641
TI  - Determination of synthetic ferric chelates used as fertilizers by liquid
      chromatography-electrospray/mass spectrometry in agricultural matrices.
AB  - A high-performance liquid chromatography-electrospray ionization/mass
      spectrometry (time of flight) method has been developed for the simultaneous
      determination of synthetic Fe(III)-chelates used as fertilizers. Analytes
      included the seven major Fe(III)-chelates used in agriculture, Fe(III)-EDTA,
      Fe(III)-DTPA, Fe(III)-HEDTA, Fe(III)-CDTA, Fe(III)-o,oEDDHA, Fe(III)-o,pEDDHA,
      and Fe(III)-EDDHMA, and the method was validated using isotope labeled
      (57)Fe(III)-chelates as internal standards. Calibration curves had R values in
      the range 0.9962-0.9997. Limits of detection and quantification were in the
      ranges 3-164 and 14-945 pmol, respectively. Analyte concentrations could be
      determined between the limits of quantification and 25 muM (racemic and meso
      Fe(III)-o,oEDDHA and Fe(III)-EDDHMA) or 50 muM (Fe(III)-EDTA, Fe(III)-HEDTA,
      Fe(III)-DTPA, Fe(III)-CDTA and Fe(III)-o,pEDDHA). The average intraday
      repeatability values were approximately 0.5 and 5% for retention time and peak
      area, respectively, whereas the interday repeatability values were approximately
      0.7 and 8% for retention time and peak area, respectively. The method was
      validated using four different agricultural matrices, including nutrient
      solution, irrigation water, soil solution, and plant xylem exudates, spiked with
      Fe(III)-chelate standards and their stable isotope-labeled corresponding
      chelates. Analyte recoveries found were in the ranges 92-101% (nutrient
      solution), 89-102% (irrigation water), 82-100% (soil solution), and 70-111%
      (plant xylem exudates). Recoveries depended on the analyte, with Fe(III)-EDTA and
      Fe(III)-DTPA showing the lowest recoveries (average values of 87 and 88%,
      respectively, for all agricultural matrices used), whereas for other analytes
      recoveries were between 91 and 101%. The method was also used to determine the
      real concentrations of Fe(III)-chelates in commercial fertilizers. Furthermore,
      the method is also capable of resolving two more synthetic Fe(III)-chelates,
      Fe(III)-EDDHSA and Fe(III)-EDDCHA, whose exact quantification is not currently
      possible because of lack of commercial standards.

PMID- 17010642
TI  - Ion calorimetry: Using mass spectrometry to measure melting points.
AB  - Calorimetry measurements have been used to probe the melting of aluminum cluster
      cations with 63 to 83 atoms. Heat capacities were determined as a function of
      temperature (from 150 to 1050 K) for size-selected cluster ions using an approach
      based on multicollision-induced dissociation. The experimental method is
      described in detail and the assumptions are critically evaluated. Most of the
      aluminum clusters in the size range examined here show a distinct peak in their
      heat capacities that is attributed to a melting transition (the peak is due to
      the latent heat). The melting temperatures are below the bulk melting point and
      show enormous fluctuations as a function of cluster size. Some clusters (for
      example, n = 64, 68, and 69) do not show peaks in their heat capacities. This
      behavior is probably due to the clusters having a disordered solid-like phase, so
      that melting occurs without a latent heat.

PMID- 17010643
TI  - How to discriminate between leucine and isoleucine by low energy ESI-TRAP MSn.
AB  - In peptide sequencing experiments involving a single step tandem mass
      acquisition, leucine and isoleucine are indistinguishable because both are
      characterized by a 113 Da mass difference from the other peptide fragments in the
      MS2 spectrum. In this work, we propose a new method to distinguish between these
      two amino acids in consecutive MSn experiments, exploiting a gas-phase
      fragmentation of isoleucine that leads to a diagnostic 69 Da ion. We used this
      method to assess the Leu/Ile residues of several synthetic peptides. The
      procedure was then tested on a tryptic digest of myoglobin, assigning the correct
      amino acid in the majority of the peptides. This work was performed with an old
      and low-resolution instrument, thus demonstrating that our method is suitable for
      a wide number of ion trap mass spectrometers, not necessarily expensive or up-to
      date.

PMID- 17010644
TI  - Ion pore properties of ionotropic glutamate receptors are modulated by a
      transplanted potassium channel selectivity filter.
AB  - The canonical potassium channel selectivity filter motif TVGYG was transplanted
      into ionotropic glutamate receptors (iGluRs) of the AMPA and NMDA subtype to test
      whether it renders the iGluRs K(+) selective. The TVGYG motif modulated several
      ion pore properties of AMPA receptor as well as NMDA receptor mutants, e.g., the
      intra- and extracellular polyamine block, current/voltage relationships, open
      channel block by MK801 and Mg(2+), and permeability for divalent cations.
      However, introduction of the selectivity filter failed to increase the K(+)
      selectivity of homomeric AMPA and heteromeric NMDA receptor complexes, which may
      be due to absence of selectivity filter-stabilizing interaction sites in the
      iGluR pore domain. Our findings indicate that even if glutamate receptors appear
      to have the intrinsic capacity for K(+) permeability, as is demonstrated by the
      prokaryotic, glutamate-gated, K(+) selective GluR0, the isolated selectivity
      filter is not able to confer K(+) permeability to the relatively unselective
      iGluR cation pore.

PMID- 17010645
TI  - The impact of temporal compression and space selection on SVM analysis of single
      subject and multi-subject fMRI data.
AB  - In the present study, we compared the effects of temporal compression (averaging
      across multiple scans) and space selection (i.e. selection of "regions of
      interest" from the whole brain) on single-subject and multi-subject
      classification of fMRI data using the support vector machine (SVM). Our aim was
      to investigate various data transformations that could be applied before training
      the SVM to retain task discriminatory variance while suppressing irrelevant
      components of variance. The data were acquired during a blocked experiment
      design: viewing unpleasant (Class 1), neutral (Class 2) and pleasant pictures
      (Class 3). In the multi-subject level analysis, we used a "leave-one-subject-out"
      approach, i.e. in each iteration, we trained the SVM using data from all but one
      subject and tested its performance in predicting the class label of the this last
      subject's data. In the single-subject level analysis, we used a "leave-one-block
      out" approach, i.e. for each subject, we selected randomly one block per
      condition to be the test block and trained the SVM using data from the remaining
      blocks. Our results showed that in a single-subject level both temporal
      compression and space selection improved the SVM accuracy. However, in a multi
      subject level, the temporal compression improved the performance of the SVM, but
      the space selection had no effect on the classification accuracy.

PMID- 17010646
TI  - Neural correlates of cognitive efficiency.
AB  - Since its inception, experimental psychology has sought to account for individual
      differences in human performance. Some neuroimaging research, involving complex
      behavioral paradigms, has suggested that faster-performing individuals show
      greater neural activity than slower performers. Other research has suggested that
      faster-performing individuals show less neural activity than slower performers.
      To examine the neural basis of individual performance differences, we had
      participants perform a simple speeded-processing task during fMRI scanning. In
      some prefrontal cortical (PFC) brain regions, faster performers showed less
      cortical activity than slower performers while in other PFC and parietal regions
      they showed greater activity. Regional-causality analysis indicated that PFC
      exerted more influence over other brain regions for slower than for faster
      individuals. These results suggest that a critical determinant of individual
      performance differences is the efficiency of interactions between brain regions
      and that slower individuals may require more prefrontal executive control than
      faster individuals to perform successfully.

PMID- 17010647
TI  - Failure of humeral fracture fixation plate in a young patient using the Philos
      system: case report.

PMID- 17010648
TI  - Frictional properties of Hartley guinea pig knees with and without proteolytic
      disruption of the articular surfaces.
AB  - OBJECTIVE: To apply a pendulum technique to detect changes in the coefficient of
      friction of the articular cartilage of the intact guinea pig tibiofemoral joint
      after proteolytic disruption. DESIGN: Twenty-two hind limbs were obtained from 11
      3-month old Hartley guinea pigs. Twenty knees were block-randomized to one of two
      treatment groups receiving injections of: (1) alpha-chymotrypsin (to disrupt the
      superficial layer of the articular surface) or (2) saline (sham; to control for
      the effects of the intra-articular injection). The legs were mounted in a
      pendulum where the knee served as the fulcrum. The decay in pendulum amplitude as
      a function of oscillation number was first recorded and the coefficient of
      friction of the joint was determined from these data before injection. Ten
      microliters of either isotonic saline or 1 Unit/microL alpha-chymotrypsin was
      then injected into the intra-articular joint space and incubated for 2h. The
      pendulum test was repeated. Changes in the coefficient of friction between the
      sham and alpha-chymotrypsin joints were compared. One additional pair of knees
      was used for histological study of the effects of the injections. RESULTS:
      Treatment with alpha-chymotrypsin significantly increased the coefficient of
      friction of the guinea pig knee by 74% while sham treatment decreased it by 8%.
      Histological sections using Gomori trichrome stain verified that the lamina
      splendens was damaged following treatment with alpha-chymotrypsin and not
      following saline treatment. CONCLUSIONS: Treatment with alpha-chymotrypsin
      induces mild cartilage surface damage and increases the coefficient of friction
      in the Hartley guinea pig knee.

PMID- 17010649
TI  - Effect of acrylamide on the cytoskeleton and apoptosis of bovine lens epithelial
      cells.
AB  - Acrylamide, a known disrupter of intermediate filaments, has been used to produce
      the collapse of vimentin filaments in bovine lens epithelial (BEL) cells, and its
      potential modulation of staurosporine-induced apoptosis has been investigated. In
      BEL cells, short treatments with acrylamide caused the collapse of vimentin
      filaments and microtubules and the almost complete disappearance of stress
      fibers, with thick f-actin bundles remaining in the cell periphery. Actin
      organization was less affected in cells pretreated with colchicine and in
      spreading cells, suggesting that extended microtubules and vimentin filaments are
      required for acrylamide to produce its maximal effects. Acrylamide alone slightly
      increased apoptosis compared to controls. However, simultaneous exposure to
      acrylamide and staurosporine for 8h produced significantly less apoptosis than
      staurosporine alone, and preincubation with acrylamide followed by staurosporine
      markedly reduced apoptosis at 8 and 24h of treatment. Acrylamide seems therefore
      to have a dual effect on BEL cell survival.

PMID- 17010650
TI  - Thin layer chromatographic analysis of glucose and maltose in estivated
      Biomphalaria glabrata snails and those infected with Schistosoma mansoni.
AB  - Thin layer chromatography was used to analyze the glucose and maltose
      concentrations of the digestive gland-gonad complex (DGG) of uninfected-estivated
      Biomphalaria glabrata snails and estivated B. glabrata patently infected with
      Schistosoma mansoni. All snails were estivated in a most chamber at a relative
      humidity of 98+/-1% and a temperature of 23+/-1 degrees C for 14 days.
      Carbohydrates were extracted from the DGG with 70% aqueous ethanol, and extracts
      were analyzed on silica gel preadsorbent plates using ethyl acetate-glacial
      acetic acid-methanol-water (60:15:15:10) mobile phase, alpha-naphthol-sulfuric
      acid detection reagent, and quantification by densitometry. The concentrations of
      glucose and maltose were significantly reduced in both uninfected-estivated
      snails and infected-estivated snails.

PMID- 17010651
TI  - Large-scale preparation and in vitro characterization of biologically active
      human placental (20 and 22K) and pituitary (20K) growth hormones: placental
      growth hormones have no lactogenic activity in humans.
AB  - Expression plasmids containing DNA sequences optimized for expression in
      Escherichia coli were prepared encoding human pituitary (hGH-N 20K) and placental
      (hGH-V 20 and 22K) growth hormones. The proteins were expressed in bacteria,
      refolded and purified to homogeneity by anion-exchange chromatography on Q
      Sepharose according to a unique protocol developed for each protein. The yields
      from 5l of fermentation culture varied between 400 and 700mg of
      electrophoretically pure, over 95% monomeric protein. Circular dichroism (CD)
      analysis revealed similarity of the purified hGHs' secondary structure to that of
      the pituitary hGH-N 22K, except for hGH-V 20K, in which the alpha-helix content
      was lower. The purified proteins were stable as a 0.1% sterile solution held at
      pH 10-11 at 4 degrees C for at least one month. All three purified hGH molecules
      formed a 1:2 complex with hGH receptor extracellular domain (hGHR-ECD), similar
      to hGH-N 22K. Binding experiments using hGHR-ECD revealed that the differences
      between the two 22K variants or between the two 20K variants were not
      significant, except that hGH-V 20K exhibited slightly lower affinity. Somatogenic
      activity was tested in vitro using FDC-P1 cell lines. Whereas the bioactivity of
      22K hGHs and hGH-N 20K in FDC-P1-9D11 cells stably transfected with hGHR was
      almost equal and two to threefold higher than that of hGH-V 20K, in FDC-P1 3B9
      cells stably transfected with rabbit (rb) GHR, the bioactivity of both 20K
      analogues was significantly (five to ninefold) lower than that of the 22K
      hormones. The lactogenic activity measured in heterologous assays (Nb2-11C cells
      and Baf/3 cells stably transfected with the long form of rabbit prolactin
      receptor) revealed that the activity of hGH-N 20K was close to that of hGH-N 22K
      in the Baf/3 cells, but 4.5-fold lower in the Nb2 cells. The activity of hGH-V
      22K was ninefold less in Nb2 cells and 55-fold less in Baf/3 cells, whereas hGH-V
      20K had no lactogenic activity in either bioassay. In contrast, in a homologous
      lactogenic assay using Baf/3 LP cells stably transfected with hPRLR, the activity
      of both placental hGHs was nil and the activity of hGH-N 20K was 4.3-fold lower
      than that of hGH-N 22K. The latter finding raises the question of whether the
      lack of intrinsic lactogenic activity in the placental hGHs that dominate during
      pregnancy has any physiological relevance.

PMID- 17010652
TI  - [Blood transfusion and ethics: new questions].
AB  - Chairman to the French Institutional Review Board, Professor Didier Sicard raises
      blood donation issues from an ethical standpoint. The contaminated blood scandal
      focused on the necessity of reducing transfusion risks and regarded blood safety
      as an ethical mandatory requirement, a debatable subject to deal with. The author
      proposes to reconsider the nature of unpaid blood donations while advising not to
      scorn the remunerated gift when such is the case. As for the use of blood, he
      questions the solutions based on a zero risk perspective, in particular an
      excessive auto-transfusional practice or a restrictive use of blood, lately
      regarded as essential. Starting from the blood donation concern this article
      leads us to think over both our society's fears and the precautionary principle
      abuses.

PMID- 17010653
TI  - [The experience of a blood-bank doctor in Chile].
AB  - Director of a blood transfusion service in Concepcion, Chili, Dr. Christina
      Martinez reports on her experience in this centre and the actions undertaken in
      order to find resources and supports, to guarantee the operation of the centre
      and to enhance voluntary blood donation.

PMID- 17010655
TI  - An approximate analytical solution to the lag period of monophenolase activity of
      tyrosinase.
AB  - Tyrosinase shows a lag period in its action on monophenols (l-tyrosine). We
      propose an approximate analytical solution for the lag period, which fulfils the
      dependences with regard to initial enzyme concentration, and initial monophenol
      concentration. Furthermore, from a study of the dependences of the lag period on
      these variables, we can determine experimentally the o-diphenol concentration in
      the steady state. The Michaelis constant of the o-diphenol in the presence of the
      monophenol can be determined from the relationship between the o-diphenol
      concentration in the steady state and the initial monophenol concentration,
      taking into consideration the experimentally calculated Michaelis constant for
      the monophenol substrate. Although this Michaelis constant is much lower than the
      Michaelis constant for diphenol in the absence of monophenol, the binding site is
      the same. A kinetic analysis of the action mechanism of tyrosinase explains this
      difference in the values of the Michaelis constants.

PMID- 17010654
TI  - Crystal structure of the C-terminal SH3 domain of the adaptor protein GADS in
      complex with SLP-76 motif peptide reveals a unique SH3-SH3 interaction.
AB  - The Grb2-like adaptor protein GADS is essential for tyrosine kinase-dependent
      signaling in T lymphocytes. Following T cell receptor ligation, GADS interacts
      through its C-terminal SH3 domain with the adaptors SLP-76 and LAT, to form a
      multiprotein signaling complex that is crucial for T cell activation. To
      understand the structural basis for the selective recognition of GADS by SLP-76,
      herein is reported the crystal structure at 1.54 Angstrom of the C-terminal SH3
      domain of GADS bound to the SLP-76 motif 233-PSIDRSTKP-241, which represents the
      minimal binding site. In addition to the unique structural features adopted by
      the bound SLP-76 peptide, the complex structure reveals a unique SH3-SH3
      interaction. This homophilic interaction, which is observed in presence of the
      SLP-76 peptide and is present in solution, extends our understanding of the
      molecular mechanisms that could be employed by modular proteins to increase their
      signaling transduction specificity.

PMID- 17010656
TI  - Traffic between the plant endoplasmic reticulum and Golgi apparatus: to the Golgi
      and beyond.
AB  - Significant advances have been made in recent years that have increased our
      understanding of the trafficking to and from membranes that are functionally
      linked to the Golgi apparatus in plants. New routes from the Golgi to organelles
      outside the secretory pathway are now being identified, revealing the importance
      of the Golgi apparatus as a major sorting station in the plant cell. This review
      discusses our current perception of Golgi structure and organization as well as
      the molecular mechanisms that direct traffic in and out of the Golgi.

PMID- 17010657
TI  - Guard cell ABA and CO2 signaling network updates and Ca2+ sensor priming
      hypothesis.
AB  - Stomatal pores in the epidermis of plants enable gas exchange between plants and
      the atmosphere, a process vital to plant life. Pairs of specialized guard cells
      surround and control stomatal apertures. Stomatal closing is induced by abscisic
      acid (ABA) and elevated CO(2) concentrations. Recent advances have been made in
      understanding ABA signaling and in characterizing CO(2) transduction mechanisms
      and CO(2) signaling mutants. In addition, models of Ca(2+)-dependent and Ca(2+)
      independent signaling in guard cells have been developed and a new hypothesis has
      been formed in which physiological stimuli are proposed to prime Ca(2+) sensors,
      thus enabling specificity in Ca(2+)-dependent signal transduction.

PMID- 17010658
TI  - Microtubule cortical array organization and plant cell morphogenesis.
AB  - Plant cell cortical microtubule arrays attain a high degree of order without the
      benefit of an organizing center such as a centrosome. New assays for molecular
      behaviors in living cells and gene discovery are yielding insight into the
      mechanisms by which acentrosomal microtubule arrays are created and organized,
      and how microtubule organization functions to modify cell form by regulating
      cellulose deposition. Surprising and potentially important behaviors of cortical
      microtubules include nucleation from the walls of established microtubules, and
      treadmilling-driven motility leading to polymer interaction, reorientation, and
      microtubule bundling. These behaviors suggest activities that can act to increase
      or decrease the local level of order in the array. The SPIRAL1 (SPR1) and SPR2
      microtubule-localized proteins and the radial swollen 6 (rsw-6) locus are
      examples of new molecules and genes that affect both microtubule array
      organization and cell growth pattern. Functional tagging of cellulose synthase
      has now allowed the dynamic relationship between cortical microtubules and the
      cell-wall-synthesizing machinery to be visualized, providing direct evidence that
      cortical microtubules can organize cellulose synthase complexes and guide their
      movement through the plasma membrane as they create the cell wall.

PMID- 17010659
TI  - Polarized growth: maintaining focus on the tip.
AB  - Tip growth, a spatially focused cell expansion, has been best characterized in
      two plant cell types: pollen tubes and root hairs. It has long been established
      that both cell types require three intracellular components for this process: a
      tip-high calcium gradient, a polarized actin cytoskeleton, and tip-directed
      vesicle trafficking. More recently, additional mechanistic parallels have been
      observed between the two cell types, including roles for ROP and Rab GTPase
      signaling, phosphoinositides, calcium-dependent protein kinases, and the exocyst.
      Uncovering pathways that control the three components is beginning to reveal a
      highly interconnected network, which we call the tip growth LENS (for
      localization enhancing network, self-sustaining), that coordinates the required
      cellular activities to allow regulated tip growth, and to maintain itself as the
      tip advances.

PMID- 17010660
TI  - Iron modulates ecto-phosphohydrolase activities in pathogenic trichomonads.
AB  - The presence of iron in the extracellular medium is essential for both in vivo
      and in vitro survival of pathogenic microorganisms, including Trichomonas
      vaginalis and Tritrichomonas foetus. In these parasites, iron is directly
      involved in the proliferation, protein expression and activation of critical
      enzymes. The purpose of this study was to investigate the role of iron in ecto
      ATPase, ecto-phophatase and secreted phosphatase activities of these
      trichomonads. We observed that trichomonads grown in iron-depleted medium
      exhibited a remarkable decrease in both ecto-ATPase and ecto-phosphatase
      activities, when compared to those cultivated under control conditions (iron-rich
      medium). Furthermore, parasites grown in iron-depleted medium restored their
      enzyme activities when they were re-inoculated into fresh iron-rich medium. We
      demonstrated that modulation of ecto-phosphohydrolase activities is due neither
      to enzyme-iron nor to substrate-iron complex formation, since iron addition
      directly to the medium where the enzymatic reactions occurred did not alter their
      activities. Previously, we had reported that a fresh clinical isolate of T.
      vaginalis was much more cytotoxic to epithelial cell monolayers than a long-term
      cultured one. In this study we witnessed that the fresh isolate of T. vaginalis
      presented higher activities to all herein investigated enzymes than the long-term
      cultured one. Altogether, our data clearly point out that iron has a pivotal role
      in the expression of phosphohydrolases in both trichomonads.

PMID- 17010661
TI  - Resonance light scattering spectroscopy study of interaction between norfloxacin
      and calf thymus DNA and its analytical application.
AB  - The interaction between norfloxacin and calf thymus double-stranded DNA (dsDNA)
      has been studied by a resonance light scattering (RLS) technique with a common
      spectrofluorometer. The characteristics of RLS spectra, the effective factors and
      optimum conditions of the reaction have been investigated. In Britton-Robinson
      (BR) buffer (pH 5.87), norfloxacin has a maximum peak 405.5 nm and the RLS
      intensity is remarkably enhanced by trace amount of calf thymus dsDNA due to the
      interaction between norfloxacin and dsDNA. The binding of norfloxacin to DNA
      forms large particles, which were characterized by RLS spectrum, scanning
      electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrum, and
      fluorescence spectrum. Based on the enhanced RLS intensity, a novel method for
      sensitive determination of calf thymus dsDNA concentration ranging from 0.02 to
      2.3 microg ml(-1) was developed. The determination limit (3 sigma) was 1.2 ng ml(
      1). The method is simple, rapid, practical and relatively free from interference
      generated by coexisting substance, as well as much more sensitive than most of
      the reported methods. Three synthetic samples of ctDNA were determined with
      satisfactory results.

PMID- 17010662
TI  - Theoretical and UV spectral study of isomeric 1-(quinolinyl)-beta-carbolines
      conformations.
AB  - On the basis of beta-carboline (1) and 1-(quinolin-2'-yl)-beta-carboline (3)
      alpha- and t-band energies differences (Delta(alpha,t)) a equilibrium
      conformations of 1-(quinolin-4'(5'-8')-yl)-beta-carbolines (4-8) in solution have
      been estimated. Furthermore, as an example of model compounds 1-(alpha'-naphtyl)
      beta-carboline (MC1) and 1-(beta'-naphtyl)-beta-carboline (MC2) and also 5 and 6
      by molecular mechanics (mm+), semi-empirical (AM1) and none empirical (RHF/6
      31G(d)) methods a computations of internal rotation of quinoline fragment around
      single bond have been performed. It was found that the greater bathochromic shift
      of the long-wavelength band maxima of 1, in the case of 3 (Deltalambda(max)=39
      nm) relatively to 6, 7 (Deltalambda(max)=17+/-2 nm) and 4, 5, 8
      (Deltalambda(max)=9+/-1 nm) caused by coplanarity of the molecule 3. Also, from
      experimental and theoretical investigations a less dihedral angle between beta
      carboline and quinoline nucleous for 6, and 7 than 4, 5 and 8 owing to steric and
      electronic interactions have been found.

PMID- 17010663
TI  - Theoretical study of electronic structures and spectroscopic properties of Ga3Sn,
      GaSn3, and their ions.
AB  - Ground and excited states of mixed gallium stannide tetramers (Ga3Sn, Ga3Sn+,
      Ga3Sn-, GaSn3, GaSn3+, and GaSn3-) are investigated employing the complete active
      space self-consistent-field (CASSCF), density function theory (DFT), and the
      coupled-cluster single and double substitution (including triple excitations)
      (CCSD(T)) methods. The ground states of Ga3Sn, Ga3Sn+, and Ga3Sn- are found to be
      the 2A1, 3B1, and 1A1 states in C2v symmetry with a planar quadrilateral
      geometry, respectively. The ground states of GaSn3 and GaSn3- is predicted to be
      the 2A1 and 1A1 states in C2v point group with a planar quadrilateral structure,
      respectively, while the ground state of GaSn3+ is the 1A1 state with ideal
      triangular pyramid C3v geometry. Equilibrium geometries, vibrational frequencies,
      binding energies, electron affinities, ionization energies, and other properties
      of Ga3Sn and GaSn3 are computed and discussed. The anion photoelectron spectra of
      Ga3Sn- and GaSn3- are also predicted. It is interesting to find that the amount
      of charge transfer between Ga and Sn2 atoms in the 1A1 state of GaSn3+ greatly
      increases upon electron ionization from the 2A1 state of GaSn3, which may be
      caused by large geometry change. On the other hand, the results of the low-lying
      states of Ga3Sn and GaSn3 are compared with those of Ga3Si and GaSi3.

PMID- 17010664
TI  - A data-gathering broker as a future-orientated approach to supporting EPR users.
AB  - With the continued expansion of electronic patient record systems ahead of
      comprehensive evidence, metrics, or future-proofing, health informatics in Europe
      and beyond is embarking on a faith-driven adventure that also risks data swamping
      of end-users. An alternative approach is an information broker system, drawing
      from departmental data sources. A 3-year study in health and social care has
      produced a first demonstrator which can search for specified information in
      heterogeneous distributed data stores, with source-specific permission can copy
      it, and then merge the search results into one integrated picture in a real-time
      process which is also captured in an audit system. The research project has
      addressed a number of issues during the study, including updating the concepts of
      role-based access, semantic interoperability, and harnessing web-based services
      bound at the time of need. A demonstrator now exists, and provides a platform for
      further application and development research. This paper summarises how this
      opens up a viable alternative approach for the next generation of health record
      systems, enabling record searching and integration as and when it is needed for
      specific patient-related purposes, whilst being independent of organisations,
      diagnostic approaches, or service delivery structures, and reducing the risks of
      data swamping.

PMID- 17010665
TI  - Evaluation of the clinical performance of the Beckman Coulter Access AbHBsII
      immunoassay for the detection of hepatitis B surface antibodies.
AB  - BACKGROUND: Hepatitis B virus (HBV) surface antibodies (anti-HBs) testing is
      useful in various clinical circumstances, including identification of HBV
      susceptible individuals in pre- and post-vaccination programs. OBJECTIVES: To
      assess the clinical performance of Beckman Coulter's anti-HBs chemiluminescence
      immunoassay (Access AbHBsII). STUDY DESIGN: Laboratory performances were
      evaluated on 1207 routine samples pre-screened with Abbott Axsym anti-HBs assay
      and divided into three different panels: vaccinated subjects (n=232), subjects
      with resolved HBV infection (n=150) and negative subjects for anti-HBs (n=825).
      Sera with discrepant results were resolved by an alternative method and further
      chart review. RESULTS: The overall concordance between Access and Axsym assays
      was 95.8%. The relative sensitivity, relative specificity, positive predictive
      value and negative predictive value were 97.8%, 98.1%, 96%, and 99%,
      respectively. Of the 51 discrepant results, eight were false negative by Access,
      fifteen were false positive by Access, including sera from seven pregnant women,
      two patients with acute leukemia, and four with inflammatory syndromes.
      CONCLUSIONS: The Beckman Coulter's Access AbHBsII assay displays satisfactory
      relative sensitivity and specificity performances. The assay has good precision
      and reliability and is technically simple and fast.

PMID- 17010666
TI  - Metabolism of phosphatidylcholine and its implications for lipid acyl chain
      composition in Saccharomyces cerevisiae.
AB  - Phosphatidylcholine (PC) is a very abundant membrane lipid in most eukaryotes
      including the model organism Saccharomyces cerevisiae. Consequently, the
      molecular species profile of PC, i.e. the ensemble of PC molecules with acyl
      chains differing in number of carbon atoms and double bonds, is important in
      determining the physical properties of eukaryotic membranes, and should be
      tightly regulated. In this review current insights in the contributions of
      biosynthesis, turnover, and remodeling by acyl chain exchange to the maintenance
      of PC homeostasis at the level of the molecular species in yeast are summarized.
      In addition, the phospholipid class-specific changes in membrane acyl chain
      composition induced by PC depletion are discussed, which identify PC as key
      player in a novel regulatory mechanism balancing the proportions of bilayer and
      non-bilayer lipids in yeast.

PMID- 17010667
TI  - Intracellular survival and replication of Neisseria meningitidis in human brain
      microvascular endothelial cells.
AB  - To cause meningitis the extracellular pathogen Neisseria meningitidis has to
      traverse the blood-cerebrospinal fluid (B-CSF) barrier. Postulating a
      transcellular passage, meningococci (MC) have been shown to adhere to and enter B
      CSF barrier forming human brain microvascular endothelial cells (HBMEC).
      Furthermore, electron microscopy studies demonstrated that intracellular MC
      reside within membrane-bound compartments, both solitary and in groups. To
      investigate the ability of MC to survive and replicate intracellularly, prolonged
      gentamicin protection assays were performed. Encapsulated bacteria were found to
      survive and, after an initial delay, to replicate within HBMEC, whereas the
      number of intracellular capsule-deficient mutants decreased continuously. This
      strongly suggests that the capsule plays a pivotal role in the intracellular
      survival of MC. Further investigations were initiated to characterise the
      membrane-bound compartment, the Neisseria-containing vacuole (NCV).
      Immunfluorescence microscopy studies showed that NCVs interact with the endocytic
      pathway acquiring the early endosomal marker protein, transferrin receptor (TfR),
      and the late endosomal/lysosomal marker protein Lamp-1.

PMID- 17010668
TI  - Defective antigen-presenting cell function in human neonates.
AB  - Immaturity of the immune system has been suggested as an underlying factor for
      the high rate of morbidity and mortality from infections in newborns. Functional
      impairment of neonatal T cells is frequently quoted as the main underlying
      mechanism for such immaturity. However, recent studies suggest that neonatal
      antigen-presenting cells (APCs) also exhibit functional alterations, which could
      lead to secondary defects of adaptive T-cell responses. In this review, we
      summarize what is known on the functionality of APC at birth and during early
      childhood. Compared to adults, neonatal APCs display markers of immaturity and
      produce low levels of cytokines. Multiple factors could be involved in neonatal
      APC alteration, such as intrinsic immaturity, defective interaction between APCs
      and T cells and regulatory T-cell-mediated inhibition. Characterization of the
      relative contribution of each mechanism is clearly needed to better understand
      the functional capability of the neonatal immune system.

PMID- 17010669
TI  - Proteolytic mapping of the adeno-associated virus capsid.
AB  - The three-dimensional structures of the viral capsid of three AAV serotypes have
      previously been determined by X-ray crystallography or cryoelectron microscopy.
      These studies of AAV and similar studies of autonomous parvoviruses have yielded
      important structural information about the virions in a low-energy conformation.
      However, there is little information on the structural properties of AAV virions
      in solution under physiological conditions. We demonstrate that proteolytic
      digestion of AAV2 virions with trypsin results in cleavage at a specific site on
      the capsid surface while the capsid remains intact. The products of digestion
      were mapped using unique antibodies, protein sequencing, mass spectroscopy, and
      3D structure modeling to a region on a surface loop that is common to all three
      AAV2 structural proteins. Empty AAV2 capsids could be distinguished from full
      (DNA-containing) capsids, having an increased susceptibility of VP2 to trypsin
      and being digested more rapidly by chymotrypsin. Proteolytic analysis utilizing
      trypsin or chymotrypsin was also capable of distinguishing AAV2 from AAV1 and
      AAV5, as seen by differential susceptibility and unique fragment patterns. These
      data demonstrate a novel approach for studying the structure of AAV capsids in
      solution and should be valuable in the testing and engineering of AAV vectors for
      gene transfer.

PMID- 17010671
TI  - Experiences of persons with epilepsy and their families as they look for medical
      and community care: a focus group study from South Carolina.
AB  - Epilepsy affects a larger number of individuals than previously thought-up to 2%
      of the population-and its effects reach further. Yet epilepsy, with its
      associated lingering stigma and fear, has remained in the background in terms of
      services and research. Traditional quantitative research often falls short when
      trying to describe the impact of epilepsy on the lives of individuals and their
      families. In the present study, focus groups were held throughout South Carolina
      to discuss individuals' experiences with accessing epilepsy-related services and
      health care, and what life with epilepsy is like. Following qualitative data
      analysis, findings included two themes. One theme focuses on the ongoing search
      for services and help. The second theme concerns the experiences of living life
      with epilepsy. Also highlighted are recommendations for potential improvements in
      public awareness and professional training, and helpful interventions.

PMID- 17010670
TI  - Anti-tumor immunotherapy via antigen delivery from a live attenuated genetically
      engineered Pseudomonas aeruginosa type III secretion system-based vector.
AB  - Immunotherapy requiring an efficient T lymphocyte response is initiated by
      antigen delivery to antigen-presenting cells. Several studies have assessed the
      efficiency of various antigen loading procedures, including microbial vectors.
      Here a live strain of Pseudomonas aeruginosa was engineered to translocate a
      recombinant antigenic protein into mammalian cells via the type III secretion
      system, a bacterial device translocating effector proteins into host cells.
      Optimization of the vector included virulence attenuation and determination of
      the N-terminal sequence allowing translocation of fused antigens into cells. In
      vitro delivery of an ovalbumin fragment by the bacterial vector into dendritic
      cells induced the activation of ovalbumin-specific CD8(+) T lymphocytes. Mice
      injected with the ovalbumin-delivering vector developed ovalbumin-specific CD8(+)
      T lymphocytes and were resistant to a subsequent challenge with an ovalbumin
      expressing melanoma. Moreover, in a curative assay, injection of the vaccine
      vector 5 and 12 days after tumor implantation led to a complete cure in five of
      six animals. These results highlight the utility of type III secretion system
      based vectors for anti-tumor immunotherapy.

PMID- 17010672
TI  - Predictors of topical anesthetic effectiveness in children.
AB  - Some children report significant pain with peripheral intravenous catheter (IV)
      insertion, despite the appropriate use of topical lidocaine anesthetics. This
      analysis of data from an existing study identified factors related to variation
      in topical anesthetic effectiveness used for IV insertion. The children (n = 218)
      in this investigation were 4 to 10 years old and undergoing a scheduled IV
      insertion. Inclusion criteria were (1) topical anesthetic was used according to
      manufacturer's recommendations, (2) DNA material was available, and (3) child
      completed a self-report measure of pain intensity (Oucher scale). Low pain
      phenotype was defined as a pain intensity score of 0 to 3, and high pain
      phenotype was an intensity score of 4 to 10. Potential predictor variables
      included child age, gender, number of previous painful procedures, state and
      trait anxiety, temperament characteristics, and alleles in 3 candidate genes in a
      pain pathway influenced by topical anesthetics (endothelin-1 [EDN1], endothelin
      receptor A [EDNRA], endothelin receptor B [EDNRB]). All subjects were genotyped
      for a single-nucleotide polymorphism in each gene. Children in the high pain
      group (n = 89) were significantly younger (P < .0001), more active (P = .0029),
      scored higher for trait (P = .0009) and state anxiety (P = .0312), and had the
      EDNRA TT genotype (high pain group, TT 67.35%; low pain group, TT 39.47%; P =
      .026). PERSPECTIVE: The identification of factors that influence peripheral pain
      sensation aids in selecting the most appropriate pharmacologic and
      nonpharmacologic interventions. Until genotyping is available at a clinically
      prescriptive level, other predictors (eg, age and activity level) can be used to
      tailor pain-relieving strategies for children undergoing needle sticks.

PMID- 17010673
TI  - Expression of neurotrophic factors in neonatal rats after peripheral
      inflammation.
AB  - Neonatal peripheral inflammatory insult might result in the alteration of
      neuronal development in the nociceptive circuit. During early postnatal period,
      neurotrophins play important roles in neural development and sensory nerve
      innervation in the central and peripheral nervous systems. In this study, we
      investigated mRNA expression for neurotrophic factors and their receptors in the
      dorsal root ganglia of rat pups during postnatal life after peripheral
      inflammation induced by injection of complete Freund's adjuvant (CFA) into hind
      paw on postnatal day 1. Our results showed that mRNA expression levels of alpha
      calcitonin gene-related peptides, tropomyosin-related kinase-A (trkA), p75
      neurotrophin receptor (p75(NTR)), and brain-derived neurotrophic factor (BDNF)
      elevated significantly after CFA treatment. Such an increase began 1 day after
      CFA treatment and lasted 2 to 3 days for trkA, p75(NTR), and BDNF. In contrast,
      there was no change in mRNA expression levels for neurotrophin-4/5, beta-nerve
      growth factor (beta-NGF), trkB, glial cell line-derived neurotrophin factor, and
      receptor protein tyrosine kinase protein. Our study demonstrated that neonatal
      peripheral inflammatory insult might result in molecular changes of neurotrophic
      factors, particularly in NGF receptors and BDNF, in the process of neuronal
      development and plasticity in primary afferents during early neonatal period.
      PERSPECTIVE: Neonatal peripheral inflammation model has been used for the
      exploration of neuropathic pain mechanism for years. This work provided further
      detailed information about possible neurotransmitters and peptides involved in
      this process. This might also lead to future clinical application.

PMID- 17010674
TI  - Gene expression-based chemical genomics identifies rapamycin as a modulator of
      MCL1 and glucocorticoid resistance.
AB  - Drug resistance remains a major obstacle to successful cancer treatment. A
      database of drug-associated gene expression profiles was screened for molecules
      whose profile overlapped with a gene expression signature of glucocorticoid (GC)
      sensitivity/resistance in acute lymphoblastic leukemia (ALL) cells. The screen
      indicated that the mTOR inhibitor rapamycin profile matched the signature of GC
      sensitivity. We tested the hypothesis that rapamycin would induce GC sensitivity
      in lymphoid malignancy cells and found that it sensitized to GC-induced apoptosis
      via modulation of antiapoptotic MCL1. These data indicate that MCL1 is an
      important regulator of GC-induced apoptosis and that the combination of rapamycin
      and glucocorticoids has potential utility in lymphoid malignancies. Furthermore,
      this approach represents a strategy for identification of promising combination
      therapies for cancer.

PMID- 17010676
TI  - Murine models of myocardial and limb ischemia: diagnostic end-points and
      relevance to clinical problems.
AB  - Ischemic disease represents the new epidemic worldwide. Animal models of ischemic
      disease are useful because they can help us to understand the underlying
      pathogenetic mechanisms and develop new therapies. The present review article
      summarizes the results of a consensus conference on the status and future
      development of experimentation in the field of cardiovascular medicine using
      murine models of peripheral and myocardial ischemia. The starting point was to
      recognize the limits of the approach, which mainly derive from species- and
      disease-related differences in cardiovascular physiology. For instance, the mouse
      heart beats at a rate 10 times faster than the human heart. Furthermore, healing
      processes are more rapid in animals, as they rely on mechanisms that may have
      lost relevance in man. The main objective of the authors was to propose general
      guidelines, diagnostic end points and relevance to clinical problems.

PMID- 17010675
TI  - Gene expression signature-based chemical genomic prediction identifies a novel
      class of HSP90 pathway modulators.
AB  - Although androgen receptor (AR)-mediated signaling is central to prostate cancer,
      the ability to modulate AR signaling states is limited. Here we establish a
      chemical genomic approach for discovery and target prediction of modulators of
      cancer phenotypes, as exemplified by AR signaling. We first identify AR
      activation inhibitors, including a group of structurally related compounds
      comprising celastrol, gedunin, and derivatives. To develop an in silico approach
      for target pathway identification, we apply a gene expression-based analysis that
      classifies HSP90 inhibitors as having similar activity to celastrol and gedunin.
      Validating this prediction, we demonstrate that celastrol and gedunin inhibit
      HSP90 activity and HSP90 clients, including AR. Broadly, this work identifies new
      modes of HSP90 modulation through a gene expression-based strategy.

PMID- 17010677
TI  - Multilocus sequence typing and genetic structure of Cryptosporidium hominis from
      children in Kolkata, India.
AB  - Endemicity of cryptosporidiosis in India has been documented with little genetic
      characterization of the parasites. Fifty Cryptosporidium-positive specimens
      collected between 2001 and 2004 from pediatric patients in Kolkata, India were
      analyzed for parasite genetic structure using multilocus sequence typing (MLST).
      Genotype analyses showed the presence of Cryptosporidium hominis, Cryptosporidium
      meleagridis and Cryptosporidium felis in 49, 2 and 1 patients, respectively (two
      patients had mixed infections of C. hominis and C. meleagridis). To assess the
      extent of genetic heterogeneity of C. hominis, minisatellites, microsatellites
      and polymorphic markers in three different chromosomes were sequenced, including
      genes encoding the 60kDa glycoprotein (GP60), a 47kDa protein (CP47), a mucin
      like protein (Mucin1), a serine repeat antigen (MSC6-7), and a 56kDa trans
      membrane protein (CP56) in chromosome 6, the 70kDa heat shock protein (HSP70) in
      chromosome 2, and a T-rich gene fragment (Chrom3T) in chromosome 3. Population
      sub-structure of C. hominis based on multilocus gene sequences showed that there
      were 25 multilocus subtypes defined by combined sequence length and nucleotide
      polymorphism, which formed four distinct groups in this population. Significant
      intra- and inter-genic linkage disequilibria were observed with minimum
      recombination or expansion of limited subtypes, all indicative of a mostly clonal
      population structure. The results highlight the importance of high resolution
      MLST in studying Cryptosporidium population sub-structure especially when length
      polymorphism may be inadequate in identifying unique subtypes. The significance
      of the diverse MLST within C. hominis in relation to geographical and temporal
      factors and clinical manifestations of disease warrants further investigations.

PMID- 17010679
TI  - Epidemiological dynamics of antimonial resistance in Leishmania donovani:
      genotyping reveals a polyclonal population structure among naturally-resistant
      clinical isolates from Nepal.
AB  - Pentavalent antimonials (SbV) are the first line drug against leishmaniasis
      worldwide, but drug resistance is increasingly reported, particularly in the
      Indian sub-continent, where it represents a major threat for the control of
      anthroponotic visceral leishmaniasis (VL). In order to understand the
      epidemiological dynamics of antimonial resistance in anthroponotic VL, we
      analysed here the population structure of 24 Leishmania donovani stocks isolated
      from anthroponotic VL-patients from Eastern Nepal: 13 SbV-naturally resistant and
      11 SbV-sensitive, as demonstrated by in vitro drug susceptibility assays. The
      parasites were genotyped by PCR-RFLP analysis of kDNA minicircles and by
      microsatellite analysis and the encountered polymorphism revealed a polyclonal
      structure among resistant isolates. Furthermore, analysis of paired samples
      obtained from the same patients before treatment and after failure revealed
      primary as well as acquired resistance. The hypothesis of independent events of
      drug resistance emergence is proposed and confronted to alternative explanations.
      Our results show the dynamics of drug resistance epidemiology and highlight the
      importance of surveillance networks.

PMID- 17010678
TI  - A comparative study of the genetic diversity of the 42kDa fragment of the
      merozoite surface protein 1 in Plasmodium falciparum and P. vivax.
AB  - We investigated the genetic diversity of the 42kDa fragment of the merozoite
      surface protein 1 (MSP-1) antigen in Plasmodium falciparum and P. vivax, as well
      as in non-human primate malarial parasites. This fragment undergoes a proteolytic
      cleavage generating two fragments of 19kDa (MSP-1(19)) and 33kDa (MSP-1(33)) that
      are critical in erythrocyte invasion. We found that overall the MSP-1(33)
      fragment exhibits greater genetic diversity than the MSP-1(19) regardless of the
      species. We have found evidence for positive natural selection only in the human
      malaria parasites by comparing the rate of non-synonymous versus synonymous
      substitutions. In addition, we found clear differences between the two major
      human malaria parasites. In the case of P. falciparum, positive natural selection
      is acting on the MSP-1(19) region while the MSP-1(33) is neutral or under
      purifying selection. The opposite pattern was observed in P. vivax. Our results
      suggest different roles of this antigen in the host-parasite immune interaction
      in each of the major human malarial parasites.

PMID- 17010680
TI  - Progesterone increases hypoxic ventilatory response and reduces apneas in newborn
      rats.
AB  - We hypothesized that progesterone may enhance the hypoxic ventilatory response
      and reduce the occurrence of apneas in newborn male rats. We studied 10-day-old
      rats chronically exposed to progesterone (Prog) or vehicle through the milk of
      lactating mothers. Respiratory and metabolic recordings were performed using
      whole body plethysmography under normoxia and during hypoxic exposure (10% O(2)-
      30 min). While progesterone did not alter baseline breathing and metabolic rate,
      it increased hypoxic ventilatory response particularly by limiting the magnitude
      of the ventilatory roll-off during the second phase of the hypoxic ventilatory
      response (i.e. following 5 min of exposure). In parallel, progesterone lowered
      the number of spontaneous apneas and drastically reduced the occurrence of post
      sigh apneas during hypoxic exposure by limiting the time of the post-sigh
      expiratory pause. Following domperidone injection (used to block peripheral D2
      dopamine receptor), minute ventilation increased in Veh pups and the number of
      spontaneous apneas decreased. These responses were not observed in Prog pups,
      suggesting that progesterone reduces peripheral dopaminergic inhibition on
      breathing. We conclude that progesterone is a potent stimulant of hypoxic
      ventilatory response in newborn rats and effectively reduces the occurrence of
      apneas.

PMID- 17010681
TI  - A stability-indicating high performance liquid chromatographic (HPLC) assay for
      the simultaneous determination of atorvastatin and amlodipine in commercial
      tablets.
AB  - A simple, rapid, precise and accurate isocratic reversed-phase stability
      indicating HPLC method was developed and validated for the simultaneous
      determination of atorvastatin (AT) and amlodipine (AM) in commercial tablets. The
      method has shown adequate separation for AM, AT from their associated main
      impurities and their degradation products. Separation was achieved on a
      Perfectsil Target ODS-3, 5 microm, 250 mm x 4.6 mm i.d. column using a mobile
      phase consisting of acetonitrile-0.025 M NaH(2)PO(4) buffer (pH 4.5) (55:45, v/v)
      at a flow rate of 1 ml/min and UV detection at 237 nm. The drugs were subjected
      to oxidation, hydrolysis, photolysis and heat to apply stress conditions. The
      linearity of the proposed method was investigated in the range of 2-30 microg/ml
      (r=0.9994) for AT and 1-20 microg/ml (r=0.9993) for AM. The limits of detection
      were 0.65 microg/ml and 0.35 microg/ml for AT and AM, respectively. The limits of
      quantitation were 2 microg/ml and 1 microg/ml for AT and AM, respectively.
      Degradation products produced as a result of stress studies did not interfere
      with the detection of AT and AM and the assay can thus be considered stability
      indicating.

PMID- 17010682
TI  - Protein arginine methylation: Cellular functions and methods of analysis.
AB  - During the last few years, new members of the growing family of protein arginine
      methyltransferases (PRMTs) have been identified and the role of arginine
      methylation in manifold cellular processes like signaling, RNA processing,
      transcription, and subcellular transport has been extensively investigated. In
      this review, we describe recent methods and findings that have yielded new
      insights into the cellular functions of arginine-methylated proteins, and we
      evaluate the currently used procedures for the detection and analysis of arginine
      methylation.

PMID- 17010683
TI  - Limitations in quantitation of the biomarker CCL18 in Gaucher disease blood
      samples by surface-enhanced laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - SELDI-TOF MS assisted the discovery of the chemokine CCL18/PARC as plasma
      biomarker for pathological storage cells in Gaucher disease patients. Prognostic
      elevation of CCL18 in blood of Gaucher patients has been confirmed by ELISA.
      Given its low molecular mass, positive charge, and relatively high abundance,
      CCL18 seems a particular attractive protein for SELDI-TOF based quantitation.
      Therefore, we determined CCL18 levels in plasma using SELDI-TOF MS and ELISA, in
      parallel. CCL18 levels in some blood samples were significantly underestimated
      when determined by SELDI-TOF MS. Spiking of recombinant CCL18 indicated that its
      detection by SELDI-TOF MS is strongly determined by the nature of the sample,
      even markedly varying between samples obtained from one donor at different time
      points. Independent of the total CCL18 concentration in blood only 1-10% of the
      chemokine bound to the ProteinChip Array. Even when comparable amounts of CCL18
      from distinct samples were bound to the ProteinChip Array, diverse peak
      intensities could be observed. Thus, limited binding capacity and sample
      dependent suppression of CCL18 ionization contribute significantly to the final
      peak intensity. In conclusion, SELDI-TOF MS offers no reliable procedure to
      quantitatively monitor CCL18 levels in blood and thus cannot be applied in
      evaluation of disease status of Gaucher patients.

PMID- 17010684
TI  - Dynamic and coordinating domain motions in the active subunits of the F1-ATPase
      molecular motor.
AB  - F1-ATPase is a rotary molecular motor crucial for various cellular functions. In
      F1-ATPase, the rotation of the gammadeltaepsilon subunits against the hexameric
      alpha(3)beta(3) subunits is highly coordinative, driven by ATP hydrolysis and
      structural changes at three beta subunits. However, the dynamical and
      coordinating structural transitions in the beta subunits are not fully understood
      at the molecular level. Here we examine structural transitions and domain motions
      in the active subunits of F1-ATPase via dynamical domain analysis of the
      alpha(3)beta(3)gammadeltaepsilon complex. The domain movement and hinge axes and
      bending residues have been identified and determined for various conformational
      changes of the beta-subunits. P-loop and the ATP-binding pocket are for the first
      time found to play essential mechanical functions additional to the catalytic
      roles. The cooperative conformational changes pertaining to the rotary mechanism
      of F1-ATPase appears to be more complex than Boyer's 'bi-site' activity. These
      findings provide unique molecular insights into dynamic and cooperative domain
      motions in F1-ATPase.

PMID- 17010685
TI  - Strontium ranelate reduces the urinary level of cartilage degradation biomarker
      CTX-II in postmenopausal women.
AB  - OBJECTIVE: Strontium ranelate significantly decreases the risk of osteoporotic
      fractures. The objective of the present study was to investigate whether
      strontium ranelate (2 g/day) also affects cartilage brakedown as measured by
      urinary marker of cartilage degradation, designated CTX-II. METHODS: A subgroup
      of 2617 postmenopausal osteoporotic women (aged 75.7+/-4.4 years) were selected
      from the TROPOS phase III study on the basis of a urinary sampling reported at
      each visit during the first three years of the study. When included in TROPOS,
      they were randomized to strontium ranelate or placebo in a double-blind fashion
      for 3 years. A calcium and vitamin D supplement was also provided to the subjects
      during the study. A marker of collagen type II degradation (CTX-II) corrected for
      urinary creatinine (CTX-II/cr.) was assessed at regular intervals throughout the
      study in 1310 patients in strontium ranelate group and 1307 patients in placebo
      group. RESULTS: The response in CTX-II depended on time (p<0.0001), and this time
      dependency differed statistically significantly between groups (time x treatment)
      (p<0.0003). In addition, there was a statistically significant difference between
      treatments (p<0.0001). The difference in the response of CTX-II/cr. appeared
      already after three months, with the strontium ranelate-treated subjects having
      approximately 15-20% lower values than the placebo-treated subjects for the
      remaining study period (p<0.0001). CONCLUSION: Treatment with strontium ranelate
      significantly decreases urinary excretion of CTX-II, a marker of cartilage
      destruction. Further studies are warranted to investigate an effect on cartilage
      formation and symptoms of osteoarthritis.

PMID- 17010687
TI  - Back pain: facts and fiction.

PMID- 17010686
TI  - PPAR agonists modulate human osteoclast formation and activity in vitro.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      steroid hormone superfamily and exist in three isoforms: PPARalpha, beta and
      gamma, each with specific functions. In this study, we have investigated the
      expression of PPARs by human osteoclast precursors and osteoclasts generated in
      vitro. In addition, the effects of fibrates and isoform-specific PPAR agonists on
      osteoclast formation and resorption in vitro were determined. Human peripheral
      blood mononuclear cells (PBMCs) were stimulated with human recombinant RANKL and
      M-CSF to generate osteoclasts. RNA was extracted at days 0, 7, 14 and 21 and RT
      PCR for all three PPAR isoforms demonstrated their expression throughout this
      culture period. To determine the effect on osteoclast formation, PPAR agonists
      (10(-8) M to 10(-5) M) were added from the beginning of the culture until day 14
      and the number of multinucleated osteoclasts counted. The effect of PPAR agonists
      on osteoclast function was similarly determined by treating mature,
      multinucleated osteoclasts cultured on dentine wafers with PPAR agonists (10(-8)
      M to 10(-5) M) for 7 days and quantifying resorption. Bezafibrate and
      fenofibrate, which non-discriminately activate all PPAR isoforms, significantly
      inhibited the formation of multinucleated osteoclasts from PBMC in vitro.
      Bezafibrate treatment of mature osteoclast resulted in 50% inhibition (at 10(-8)
      M and 10(-7) M) of resorption, yet fenofibrate had no significant effect.
      Activation of individual PPARs with isoform-specific agonist (GW9578, L165041 and
      ciglitizone which preferentially activate PPARalpha, beta and gamma respectively)
      resulted in significant dose-dependent inhibition of multinucleated osteoclast
      formation. Divergent effects on osteoclast resorption were observed; GW9578 had
      no significant effect on resorption, whereas ciglitizone and L165041 dose
      dependently inhibited and stimulated resorption, respectively. These data show
      for the first time expression of all three PPAR isoforms throughout the
      development and maturation period of osteoclasts generated from human PBMCs. In
      addition, we demonstrate that isoform-specific PPAR agonists have strong effects
      on multinucleation and highly variable effects on bone resorption. In conclusion,
      this study highlights the potential of PPARs as therapeutic targets in diseases
      with accelerated osteoclast formation and resorption.

PMID- 17010689
TI  - Case of the season: aneurysmal dilatation of the small bowel (not only lymphoma).

PMID- 17010690
TI  - Current classification and imaging of congenital spinal abnormalities.

PMID- 17010692
TI  - Diffusion-weighted magnetic resonance imaging of the spine and spinal cord.

PMID- 17010693
TI  - Imaging of the postoperative spine.

PMID- 17010691
TI  - Imaging of spinal and spinal cord tumors.

PMID- 17010694
TI  - Degenerative disorders of the spine.

PMID- 17010695
TI  - Imaging of spinal infections.

PMID- 17010696
TI  - Physiology of Zymomonas mobilis: some unanswered questions.
AB  - The ethanol-producing bacterium Zymomonas mobilis can serve as a model organism
      for the study of rapid catabolism and inefficient energy conversion in bacteria.
      Some basic aspects of its physiology still remain poorly understood. Here, the
      energy-spilling pathways during uncoupled growth, the structure and function of
      electron transport chain, and the possible reasons for the inefficient oxidative
      phosphorylation are analysed. Also, the interaction between ethanol synthesis and
      respiration is considered. The search for mechanisms of futile transmembrane
      proton cycling, as well as identification of respiratory electron transport
      complexes, like the energy-coupling NAD(P)H:quinone oxidoreductase and the
      cyanide-sensitive terminal oxidase(s), are outlined as the key problems for
      further research of Z. mobilis energy metabolism.

PMID- 17010697
TI  - Surface adhesins of Staphylococcus aureus.
AB  - An important facet in the interaction between Staphylococcus aureus and its host
      is the ability of the bacterium to adhere to human extracellular matrix
      components and serum proteins. In order to colonise the host and disseminate, it
      uses a wide range of strategies, the molecular and genetic basis of which are
      multifactorial, with extensive functional overlap between adhesins. Here, we
      describe the current knowledge of the molecular features of the adhesive
      components of S. aureus, mechanisms of adhesion and the impact that these have on
      host-pathogen interaction.

PMID- 17010700
TI  - Retinogeniculate connections: A balancing act between connection specificity and
      receptive field diversity.
AB  - Retinogeniculate connections are one of the most striking examples of connection
      specificity within the visual pathway. In almost every connection there is one
      dominant afferent cell per geniculate cell, and both afferent and geniculate
      cells have very similar receptive fields. The remarkable specificity and strength
      of retinogeniculate connections have inspired comparisons of the lateral
      geniculate nucleus (LGN) with a simple relay that connects the retina with the
      visual cortex. However, because each retinal ganglion cell diverges to innervate
      multiple cells in the LGN, most geniculate cells must receive additional inputs
      from other retinal afferents that are not the dominant ones. These additional
      afferents make weaker connections and their receptive fields are not as perfectly
      matched with the geniculate target as the dominant afferent. We argue that these
      'match imperfections' are important to create receptive field diversity among the
      cells that represent each point of visual space in the LGN. We propose that the
      convergence of dominant and weak retinal afferents in the LGN multiplexes the
      array of retinal ganglion cells by creating receptive fields that have a richer
      range of positions, sizes and response time courses than those available at the
      ganglion cell layer of the retina.

PMID- 17010701
TI  - Double-bouquet cells in the monkey and human cerebral cortex with special
      reference to areas 17 and 18.
AB  - The detailed microanatomical study of the human cerebral cortex began in 1899
      with the experiments of Santiago Ramon y Cajal, who applied the Golgi method to
      define the structure of the visual, motor, auditory and olfactory cortex. In the
      first article of this series, he described a special type of interneuron in the
      visual cortex capable of exerting its influence in the vertical dimension. These
      neurons are now more commonly referred to as double-bouquet cells (DBCs). The
      DBCs are readily distinguished owing to their characteristic axons that give rise
      to tightly interwoven bundles of long, vertically oriented axonal collaterals
      resembling a horsetail (DBC horsetail). Nevertheless, the most striking
      characteristic of these neurons is that they are so numerous and regularly
      distributed that the DBC horsetails form a microcolumnar structure. In addition,
      DBCs establish hundreds of inhibitory synapses within a very narrow column of
      cortical tissue. These features have generated considerable interest in DBCs over
      recent years, principally among those researchers interested in the analysis of
      cortical circuits. In the present chapter, we shall discuss the morphology,
      synaptic connections and neurochemical features of DBCs that have been defined
      through the study of these cells in different cortical areas and species. We will
      mainly consider the immunocytochemical studies of DBCs that have been carried out
      in the visual cortex (areas 17 and 18) of human and macaque monkey. We will see
      that there are important differences in the morphology, number and distribution
      of DBC horsetails between areas 17 and 18 in the primate. This suggests important
      differences in the microcolumnar organization between these areas, the functional
      significance of which awaits detailed correlative physiological and
      microanatomical studies.

PMID- 17010702
TI  - Covert attention increases contrast sensitivity: Psychophysical,
      neurophysiological and neuroimaging studies.
AB  - This chapter focuses on the effect of covert spatial attention on contrast
      sensitivity, a basic visual dimension where the best mechanistic understanding of
      attention has been achieved. I discuss how models of contrast sensitivity, as
      well as the confluence of psychophysical, single-unit recording, and neuroimaging
      studies, suggest that attention increases contrast sensitivity via contrast gain,
      an effect akin to a change in the physical contrast stimulus. I suggest possible
      research directions and ways to strengthen the interaction among different levels
      of analysis to further our understanding of visual attention.

PMID- 17010704
TI  - The generation of receptive-field structure in cat primary visual cortex.
AB  - Cells in primary visual cortex show a remarkable variety of receptive-field
      structures. In spite of the extensive experimental and theoretical effort over
      the past 50 years, it has been difficult to establish how this diversity of
      functional-response properties emerges in the cortex. One of the reasons is that
      while functional studies in the early visual pathway have been usually carried
      out in vivo with extracellular recording techniques, investigations about the
      precise structure of the cortical network have mainly been conducted in vitro.
      Thus, the link between structure and function has rarely been explicitly
      established, remaining a well-known controversial issue. In this chapter, I
      review recent data that simultaneously combines anatomy with physiology at the
      intracellular level; trying to understand how the primary visual cortex
      transforms the information it receives from the thalamus to generate receptive
      field structure, contrast-invariant orientation tuning and other functional
      response properties.

PMID- 17010706
TI  - Cortical cartography revisited: A frequency perspective on the functional
      architecture of visual cortex.
AB  - Viewed in the plane of the cortical surface, the visual cortex is composed of
      overlapping functional maps that represent stimulus features such as edge
      orientation, direction of motion, and spatial frequency. Spatial relationships
      between these maps are thought to ensure that all combinations of stimulus
      features are represented uniformly across the visual field. Implicit in this view
      is the assumption that feature combinations are represented in the form of a
      place code such that a given pattern of activity uniquely signifies a specific
      combination of stimulus features. Here we review results of experiments that
      challenge the place code model for the representation of feature combinations.
      Rather than overlapping maps of stimulus features, we suggest that patterns of
      activity evoked by complex stimuli are best understood in the context of a single
      map of spatiotemporal energy.

PMID- 17010705
TI  - Contribution of feedforward, lateral and feedback connections to the classical
      receptive field center and extra-classical receptive field surround of primate V1
      neurons.
AB  - A central question in visual neuroscience is what circuits generate the responses
      of neurons in the primary visual cortex (V1). V1 neurons respond best to oriented
      stimuli of optimal size within their receptive field (RF) center. This size
      tuning is contrast dependent, i.e. a neuron's optimal stimulus size measured at
      high contrast (the high-contrast summation RF, or hsRF) is smaller than when
      measured using low-contrast stimuli (the low-contrast summation RF, or lsRF).
      Responses to stimuli in the RF center are usually suppressed by iso-oriented
      stimuli in the extra-classical RF surround. Iso-orientation surround suppression
      is fast and long range, extending well beyond the size of V1 cells' lsRF.
      Geniculocortical feedforward (FF), V1 lateral and extrastriate feedback (FB)
      connections to V1 could all contribute to generating the RF center and surround
      of V1 neurons. Studies on the spatio-temporal properties and functional
      organization of these connections can help disclose their specific contributions
      to the responses of V1 cells. These studies, reviewed in this chapter, have shown
      that FF afferents to V1 integrate signals within the hsRF of V1 cells; V1 lateral
      connections are commensurate with the size of the lsRF and may, thus, underlie
      contrast-dependent changes in spatial summation, and modulatory effects arising
      from the surround region closer to the RF center (the "near" surround). The
      spatial and temporal properties of lateral connections cannot account for the
      dimensions and onset latency of modulation arising from more distant regions of
      the surround (the "far" surround). Inter-areal FB connections to V1, instead, are
      commensurate with the full spatial range of center and surround responses, and
      show fast conduction velocity consistent with the short onset latency of
      modulation arising from the "far" surround. We review data showing that a subset
      of FB connections terminate in a patchy fashion in V1, and show modular and
      orientation specificity, consistent with their proposed role in orientation
      specific center-surround interactions. We propose specific mechanisms by which
      each connection type contributes to the RF center and surround of V1 neurons, and
      implement these hypotheses into a recurrent network model. We show physiological
      data in support of the model's predictions, revealing that modulation from the
      "far" surround is not always suppressive, but can be facilitatory under specific
      stimulus conditions.

PMID- 17010707
TI  - The sensitivity of primate STS neurons to walking sequences and to the degree of
      articulation in static images.
AB  - We readily use the form of human figures to determine if they are moving. Human
      figures that have arms and legs outstretched (articulated) appear to be moving
      more than figures where the arms and legs are near the body (standing). We tested
      whether neurons in the macaque monkey superior temporal sulcus (STS), a region
      known to be involved in processing social stimuli, were sensitive to the degree
      of articulation of a static human figure. Additionally, we tested sensitivity to
      the same stimuli within forward and backward walking sequences. We found that 57%
      of cells that responded to the static image of a human figure was also sensitive
      to the degree of articulation of the figure. Some cells displayed selective
      responses for articulated postures, while others (in equal numbers) displayed
      selective responses for standing postures. Cells selective for static images of
      articulated figures were more likely to respond to movies of walking forwards
      than walking backwards. Cells selective for static images of standing figures
      were more likely to respond to movies of walking backwards than forwards. An
      association between form sensitivity and walking sensitivity could be consistent
      with an interpretation that cell responses to articulated figures act as an
      implied motion signal.

PMID- 17010709
TI  - Fixational eye movements in normal and pathological vision.
AB  - Most of our visual experience is driven by the eye movements we produce while we
      fixate our gaze. In a sense, our visual system thus has a built-in contradiction:
      when we direct our gaze at an object of interest, our eyes are never still.
      Therefore the perception, physiology, and computational modeling of fixational
      eye movements is critical to our understanding of vision in general, and also to
      the understanding of the neural computations that work to overcome neural
      adaptation in normal subjects as well as in clinical patients. Moreover, because
      we are not aware of our fixational eye movements, they can also help us
      understand the underpinnings of visual awareness. Research in the field of
      fixational eye movements faded in importance for several decades during the late
      20th century. However, new electrophysiological and psychophysical data have now
      rejuvenated the field. The last decade has brought significant advances to our
      understanding of the neuronal and perceptual effects of fixational eye movements,
      with crucial implications for neural coding, visual awareness, and perception in
      normal and pathological vision. This chapter will review the type of neural
      activity generated by fixational eye movements at different levels in the visual
      system, as well as the importance of fixational eye movements for visual
      perception in normal vision and in visual disease. Special attention will be
      given to microsaccades, the fastest and largest type of fixational eye movement.

PMID- 17010710
TI  - Microsaccades: A microcosm for research on oculomotor control, attention, and
      visual perception.
AB  - Miniature eye movements occur involuntarily during visual fixation. The most
      prominent contribution to these fixational eye movements is generated by
      microsaccades, which are rapid small-amplitude saccades with a rate of about one
      per second. Recent work demonstrates that microsaccades are optimized to
      counteract perceptual fading during perception of a stationary scene.
      Furthermore, microsaccades are modulated by visual attention and turned out to
      generate rich spatio-temporal dynamics. We conclude that the investigation of
      microsaccades will evolve into a new research field contributing to many facets
      of oculomotor control, visual perception, and the allocation of attention.

PMID- 17010711
TI  - Fixational eye movements and motion perception.
AB  - Small eye movements are necessary for maintained visibility of the static scene,
      but at the same time they randomly oscillate the retinal image, so the visual
      system must compensate for such motions to yield the stable visual world.
      According to the theory of visual stabilization based on retinal motion signals,
      objects are perceived to move only if their retinal images make spatially
      differential motions with respect to some baseline movement probably due to eye
      movements. Motion illusions favoring this theory are demonstrated, and
      psychophysical as well as brain-imaging studies on the illusions are reviewed. It
      is argued that perceptual stability is established through interactions between
      motion-energy detection at an early stage and spatial differentiation of motion
      at a later stage. As such, image oscillations originating in fixational eye
      movements go unnoticed perceptually, and it is also shown that image oscillations
      are, though unnoticed, working as a limiting factor of motion detection. Finally,
      the functional importance of non-differential, global motion signals are
      discussed in relation to visual stability during large-scale eye movements as
      well as heading estimation.

PMID- 17010712
TI  - A cholinergic mechanism underlies persistent neural activity necessary for eye
      fixation.
AB  - It is generally accepted that the prepositus hypoglossi (PH) nucleus is the site
      where horizontal eye-velocity signals are integrated into eye-position ones.
      However, how does this neural structure produce the sustained activity necessary
      for eye fixation? The generation of the neural activity responsible for eye
      position signals has been studied here using both in vivo and in vitro
      preparations. Rat sagittal brainstem slices including the PH nucleus and the
      paramedian pontine reticular formation (PPRF) rostral to the abducens nucleus
      were used for recording intracellularly the synaptic activation of PH neurons
      from the PPRF. Single electrical pulses applied to the PPRF showed a monosynaptic
      projection on PH neurons. This synapse was found to be glutamatergic in nature,
      acting on alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA)/kainate
      receptors. Train stimulation (100 ms, 50-200 Hz) of the PPRF evoked a
      depolarization of PH neurons, exceeding (by hundreds of ms) the duration of the
      stimulus. Both duration and amplitude of this long-lasting depolarization were
      linearly related to train frequency. The train-evoked sustained depolarization
      was demonstrated to be the result of the additional activation of cholinergic
      fibers projecting onto PH neurons, because it was prevented by slice superfusion
      with atropine sulfate and pirenzepine (two cholinergic antagonists), and mimicked
      by carbachol and McN-A-343 (two cholinergic agonists). These results were
      confirmed in alert behaving cats. Microinjections of atropine and pirenzepine
      evoked an ipsilateral gaze-holding deficit consisting of an exponential-like,
      centripetal eye movement following saccades directed toward the injected site.
      These findings suggest that the sustained activity present in PH neurons carrying
      eye-position signals is the result of the combined action of PPRF neurons and the
      facilitative role of cholinergic terminals, both impinging on PH neurons. The
      present results are discussed in relation to other proposals regarding
      integrative properties of PH neurons and/or related neural circuits.

PMID- 17010714
TI  - Perceptual filling-in: More than the eye can see.
AB  - When a gray figure is surrounded by a background of dynamic texture, fixating
      away from the figure for several seconds will result in an illusory replacement
      of the figure by its background. This visual illusion is referred to as
      perceptual filling-in. The study of filling-in is important, because the
      underlying neural processes compensate for imperfections in our visual system
      (e.g., the blind spot) and contribute to normal surface perception. A long
      standing question has been whether perceptual filling-in results from symbolic
      tagging of surface regions in higher order cortex (ignoring the absence of
      information), or from active neural interpolation in lower order visual areas
      (active filling-in of information). The present chapter reviews a number of
      psychophysical studies in human subjects and physiological experiments in monkeys
      to evaluate the above two hypotheses. The data combined show that there is strong
      evidence for neural interpolation processes in retinotopically organized, lower
      order areas, but that there is also a role for higher order perceptual and
      cognitive factors such as attention.

PMID- 17010715
TI  - The visual phantom illusion: A perceptual product of surface completion depending
      on brightness and contrast.
AB  - The visual phantom illusion was first discovered by Rosenbach in 1902 and named
      'moving phantoms' by Tynan and Sekuler in 1975 because of its strong dependence
      on motion. It was later revealed that phantoms can be generated by flickering the
      grating (flickering phantoms) or by low-luminance stationary gratings under dark
      adaptation (stationary phantoms). Although phantoms are much more visible at
      scotopic or mesopic adaptation levels (scotopic phantoms) than at photopic
      levels, we proposed a new phantom illusion which is fully visible in photopic
      vision (photopic phantoms). In 2001, we revealed that the visual phantom illusion
      is a higher-order perceptual construct or a Gestalt, which depends on the
      mechanism of perceptual transparency. Perceptual transparency is known as a
      perceptual product based upon brightness and contrast. We furthermore manifested
      the shared mechanisms between visual phantoms and neon color spreading or between
      visual phantoms and the Petter effect. In our recent study, the visual phantom
      illusion can also be seen with a stimulus of contrast-modulated gratings. We
      assume that this effect also depends on perceptual transparency induced by
      contrast modulation. Moreover, we found that the Craik-O'Brien-Cornsweet effect
      and other brightness illusions can generate the visual phantom illusion. In any
      case, we explain the visual phantom illusion in terms of surface completion,
      which is given by perceptual transparency.

PMID- 17010717
TI  - Bayesian inference of form and shape.
AB  - The ability to visually perceive two-dimensional (2D) form and three-dimensional
      (3D) shape is one of our most fundamental faculties. This ability relies on
      considerable prior knowledge about the way edge elements in an image are likely
      to be connected together into a contour as well as the way these 2D contours
      relate to 3D shapes. The interaction of prior knowledge with image information is
      well modeled within a Bayesian framework. We review here the experimental
      evidence of shape perception seen as a Bayesian inference problem.

PMID- 17010718
TI  - Contour discontinuities subserve two types of form analysis that underlie motion
      processing.
AB  - Form analysis subserves motion processing in at least two ways: first, in terms
      of figural segmentation dedicated to solving the problem of figure-to-figure
      matching over time, and second, in terms of defining trackable features whose
      unambiguous motion signals can be generalized to ambiguously moving portions of
      an object. The former is a primarily ventral process involving the lateral
      occipital complex and also retinotopic areas such as V2 and V4, and the latter is
      a dorsal process involving V3A. Contour discontinuities, such as corners, deep
      concavities, maxima of positive curvature, junctions, and terminators, play a
      central role in both types of form analysis. Transformational apparent motion
      will be discussed in the context of figural segmentation and matching, and
      rotational motion in the context of trackable features. In both cases the
      analysis of form must proceed in parallel with the analysis of motion, in order
      to constrain the ongoing analysis of motion.

PMID- 17010719
TI  - Neural basis of shape representation in the primate brain.
AB  - Visual shape recognition--the ability to recognize a wide variety of shapes
      regardless of their size, position, view, clutter and ambient lighting--is a
      remarkable ability essential for complex behavior. In the primate brain, this
      depends on information processing in a multistage pathway running from primary
      visual cortex (V1), where cells encode local orientation and spatial frequency
      information, to the inferotemporal cortex (IT), where cells respond selectively
      to complex shapes. A fundamental question yet to be answered is how the local
      orientation signals (in V1) are transformed into selectivity for complex shapes
      (in IT). To gain insights into the underlying mechanisms we investigated the
      neural basis of shape representation in area V4, an intermediate stage in this
      processing hierarchy. Theoretical considerations and psychophysical evidence
      suggest that contour features, i.e. angles and curves along an object contour,
      may serve as the basis of representation at intermediate stages of shape
      processing. To test this hypothesis we studied the response properties of single
      units in area V4 of primates. We first demonstrated that V4 neurons show strong
      systematic tuning for the orientation and acuteness of angles and curves when
      presented in isolation within the cells' receptive field. Next, we found that
      responses to complex shapes were dictated by the curvature at a specific boundary
      location within the shape. Finally, using basis function decoding, we
      demonstrated that an ensemble of V4 neurons could successfully encode complete
      shapes as aggregates of boundary fragments. These findings identify curvature as
      a basis of shape representation in area V4 and provide insights into the
      neurophysiological basis for the salience of convex curves in shape perception.

PMID- 17010720
TI  - The role of familiarity in the recognition of static and dynamic objects.
AB  - Although the perception of our world is experienced as effortless, the processes
      that underlie object recognition in the brain are often difficult to determine.
      In this chapter, we review the effects of familiarity on the recognition of
      moving or static objects. In particular, we concentrate on exemplar-level stimuli
      such as walking humans, unfamiliar objects and faces. We found that the
      perception of these objects can be affected by their familiarity; for example the
      learned view of an object or the learned dynamic pattern can influence object
      perception. Deviations in the viewpoint from the familiar viewpoint, or changes
      in the temporal pattern of the objects can result in some reduction of efficiency
      in the perception of the object. Furthermore, more efficient sex categorization
      and crossmodal matching were found for familiar than for unfamiliar faces. In
      sum, we find that our perceptual system is organized around familiar events and
      that perception is most efficient with these learned events.

PMID- 17010721
TI  - Drug delivery systems in urology--getting "smarter".

PMID- 17010722
TI  - Selective ablation of symptomatic dominant renal cysts using 99% ethanol in adult
      polycystic kidney disease.
AB  - OBJECTIVES: To evaluate the clinical efficacy and outcome of 99% ethanol as a
      sclerosing agent for managing chronic flank pain due to dominant cysts in
      selected patients with adult polycystic kidney disease. Traditionally, such
      patients have been treated with analgesics and surgical/laparoscopic deroofing.
      Cyst aspiration sclerotherapy is a minimally invasive therapeutic option for such
      patients, and limited published data exist on this subject. This formed the basis
      for the present study. METHODS: A pilot study was undertaken during a 1-year
      period to evaluate the clinical efficacy of ultrasound-guided cyst aspiration
      ethanol injection sclerotherapy in 15 preselected patients with diagnosed adult
      polycystic kidney disease. All punctures were performed with strict aseptic
      precautions and local anesthesia on an outpatient basis. The patients were
      evaluated with serial scans, pain scores, and serum creatinine values. RESULTS: A
      total of 48 dominant cysts were successfully treated in all 15 patients with
      regard to cyst aspiration and shrinkage. At the end of 1 year, the pain and
      dominant cysts had completely disappeared in 13 patients and had recurred in 2;
      repeat cyst aspiration and sclerotherapy was done in 3 patients. Nephrocutaneous
      fistula and urinary tract infection occurred in 1 patient each. The decrease in
      the pain score and the rise in the serum creatinine level were statistically
      significant at P <0.05 and P <0.001, respectively. CONCLUSIONS: Alcohol cyst
      sclerotherapy is a minimally invasive, safe, and effective alternative to
      conventional surgical/laparoscopic deroofing for managing chronic flank pain due
      to adult polycystic kidney disease in selected patients. It should be considered
      as a safe and viable therapeutic option in patients in whom the primary symptom
      is chronic flank pain due to one or more dominant cysts.

PMID- 17010727
TI  - Preventing retrograde stone displacement during pneumatic lithotripsy for
      ureteral calculi using lidocaine jelly.
AB  - OBJECTIVES: To assess the efficacy of lubricating jelly instillation proximal to
      the upper ureteral calculi during lithotripsy on the prevention of retrograde
      stone displacement and the stone-free rate. METHODS: Thirty-four patients with
      upper ureteral calculi of less than 2 cm were randomized into two groups: jelly
      instillation (n = 16) and controls (n = 18). Ureteroscopy was performed using a
      9.8F semirigid ureteroscope. A 5F ureteral stent was advanced beyond the stone.
      Lidocaine jelly (2 mL) was instilled, and lithotripsy was done with a Swiss
      Lithoclast. A 5F ureteral catheter was left in place for 24 hours, and patients
      were followed up at 24 hours with radiography of the kidneys, ureters, and
      bladder and at 2 weeks with intravenous urography. RESULTS: Both groups were
      comparable in terms of mean age and stone size. Stone or stone fragment migration
      occurred in 12.4% of the treatment group and 44.4% of the controls, statistically
      significantly different (P = 0.046). The stone-free rate was 93.7% and 83.3% in
      the treatment and control groups, respectively. The rates did not improve after 2
      weeks, and the difference was not statistically significant between the two
      groups (P = 0.384). The mean operative time was also comparable between the two
      groups. CONCLUSIONS: Lidocaine jelly instillation proximal to the ureteral
      calculi during lithotripsy is an effective method to prevent retrograde stone
      displacement, but its effect on improving the stone-free rate was not significant
      in our study. Larger studies are needed to disclose more details about the
      efficacy of this method.

PMID- 17010728
TI  - Prostate-specific antigen doubling time is associated with survival in men with
      hormone-refractory prostate cancer.
AB  - OBJECTIVES: Men with metastatic hormone-refractory prostate cancer (HRPC) form a
      heterogeneous population with a wide range of symptoms and variable survival.
      Patient selection is critical in determining which patients will receive the most
      benefit from aggressive chemotherapy. The prostate-specific antigen (PSA)
      doubling time (PSADT) has been shown to be a surrogate for survival in earlier
      stages of prostate cancer, but its utility as a predictor in HRPC is unknown.
      METHODS: A retrospective chart review of 224 patients with HRPC treated from 1998
      to 2002 was performed. Eligible patients had HRPC and evidence of metastatic
      disease. The PSADT at HRPC diagnosis was calculated, and the optimal PSADT
      stratification was obtained using the log-rank chi-square statistic. Kaplan-Meier
      curves were used to estimate overall survival between the groups. RESULTS: During
      the follow-up period, 80% of patients died, 93% of prostate cancer. Overall, the
      median survival from diagnosis of HRPC was 15.1 months (range 0.5 to 90.5). The
      optimal PSADT stratification for survival was 70 days. Patients with a PSADT of
      70 days or less survived 11 months compared with 19 months for those with a PSADT
      of more than 70 days [relative risk (RR) 1.79, P <0.0001]. CONCLUSIONS: PSADT
      serves as an independent prognostic marker for survival in patients with
      metastatic HRPC. Men with a PSADT of 70 days or less had a significantly shorter
      survival time compared with men with a PSADT of more than 70 days. Inclusion of
      PSADT with other clinical data could help clinicians select men at high risk of
      early mortality who may most benefit from aggressive treatment regimens, such as
      docetaxel-based regimens.

PMID- 17010729
TI  - Anatomic nerve-sparing laparoscopic radical prostatectomy: comparison of
      retrograde and antegrade techniques.
AB  - OBJECTIVES: To compare the anatomic retrograde and antegrade preservation of the
      neurovascular bundle (NVB) during laparoscopic radical prostatectomy. METHODS:
      Anatomic studies were reviewed, focusing on the fascial layers surrounding the
      prostate and NVB and the terminology used as described by Walsh and colleagues.
      Important operative steps have been illustrated using video clips. For the
      retrograde technique, after incision of levator fascia, the NVBs were released
      from the apex before division of the urethra. Along the plane between the
      laterally incised Denonvilliers and perirectal fascia, the prostate was mobilized
      from the rectum. Isolated clipping of the seminal vesicle arteries was performed
      in an antegrade manner, followed by control of the lateral pedicles, and
      identification of the course of the NVB. For the antegrade technique, after
      dissection of the seminal vesicles, the levator fascia was incised to develop a
      lateral NVB groove. After bladder neck division and lateral pedicle ligation, the
      lateral NVB groove was used as a guide for antegrade preservation of the NVB.
      During anastomosis, the NVBs located at the 5-o'clock and 7-o'clock positions
      were avoided in both techniques. RESULTS: A questionnaire-based potency rate of
      67% and 76%, respectively, was reported after bilateral nerve sparing using
      retrograde and antegrade laparoscopic radical prostatectomy techniques.
      CONCLUSIONS: Both techniques allowed replication of open surgical principles. The
      video magnification enabled excellent demonstration of the periprostatic anatomy.
      The principles of interfascial dissection of the NVB, use of task-specific
      instrumentation, and avoiding energy sources around the NVB may be more important
      than the actual nerve-preservation technique used.

PMID- 17010732
TI  - Tumor characteristics and prognostic factors in two subsequent screening rounds
      with four-year interval within prostate cancer screening trial, ERSPC Rotterdam.
AB  - OBJECTIVES: To evaluate the tumor characteristics and prognostic factors in
      screen-detected prostate cancers in two successive screening rounds with a 4-year
      screening interval in the European Randomized Study of Screening for Prostate
      Cancer, section Rotterdam. METHODS: From 1993 to 2000, 42,376 men (21,210 in the
      screening arm and 21,166 in the control arm) were randomized and screened.
      Prostate-specific antigen testing, digital rectal examination, transrectal
      ultrasonography, and sextant biopsies were offered to the participants in the
      screening arm. A total of 1218 men with a biopsy indication at the first
      screening received an additional screening after 1 year (early recall). By 2004,
      all men had received their second screening. Interval carcinomas were defined as
      cancers detected during the screening interval and were identified by linkage
      with the Cancer Registry. RESULTS: In the first round, 1014 prostate cancers were
      detected--24 in the men noncompliant to screening, 63 at the early recall
      screening, and 433 in the second round of screening. Also, 62 interval carcinomas
      were diagnosed. In the second screening round, the mean prostate-specific antigen
      value was lower (5.6 versus 11.1 ng/mL), advanced clinical stage T3-T4 was 7.1
      fold less common, and 76.4% versus 61.5% of the biopsy Gleason scores were less
      than 7. In the first screening round, 13 regional and 9 distant metastases were
      detected; in the second round, 2 cases with distant metastasis were found.
      CONCLUSIONS: Overall, a shift toward more favorable tumor characteristics was
      seen for the second round of screening. These results support the screening
      methods used and the interscreening interval of 4 years.

PMID- 17010733
TI  - Positive effect of prostaglandin on regulation of prostatic blood flow.
AB  - OBJECTIVES: To investigate the effects of prostaglandin E2 (PGE2) and its
      antireceptor antibody on prostatic blood flow regulation using a rat model. We
      estimated that PGE2 participated in the signaling pathway of hormonal regulation
      of the prostatic blood flow. METHODS: The rats were castrated and injected
      locally with dihydrotestosterone (200 ng/head) or PGE2 (250 ng/head) directly
      into the prostatic membrane. After local dihydrotestosterone or PGE2
      administration, anti-PGE2 receptor antibody (200 ng/head) was injected locally to
      investigate interruption of the signaling pathway. After administration, we
      evaluated the relative prostatic blood flow using a laser blood flow meter. The
      change in cyclooxgenase-2 mRNA expression and the changes in PGE2 concentration
      in response to androgen stimulation were also examined. RESULTS: PGE2 was
      involved in blood flow regulation with activity equal to that of androgen. The
      effect of dihydrotestosterone was abolished by coadministration with anti-PGE2
      receptor antibody. Cyclooxgenase-2 gene expression was upregulated in response to
      androgen stimulation. The PGE2 concentration also increased in response to
      androgen stimulation. CONCLUSIONS: Our finding of PGE2 participation in androgen
      regulation of prostatic blood flow might lead to pathophysiologic elucidation of
      prostatic diseases.

PMID- 17010734
TI  - Pityriasis lichenoides and its subtypes.
AB  - Pityriasis lichenoides represents a unique group of inflammatory skin disorders
      that include pityriasis lichenoides et varioliformis acuta (PLEVA), febrile
      ulceronecrotic Mucha-Habermann disease (a subtype of PLEVA), and pityriasis
      lichenoides chronica. The history, epidemiology, clinical features,
      pathophysiology, and treatment of this group of conditions are reviewed in this
      manuscript.

PMID- 17010735
TI  - The epidemiology of sunburn in the US population in 2003.
AB  - BACKGROUND: Sunburn is a major preventable risk factor for skin cancer.
      OBJECTIVE: We investigated risk factors for sunburn in the United States based on
      the 2003 Behavioral Risk Factor Surveillance System. DESIGN AND METHODS: A random
      sample of 207,776 respondents provided data for the population-based survey. The
      main outcome measure was any report of sunburn within the previous 12 months.
      RESULTS: Overall, 39% of respondents had at least one sunburn. The strongest
      factors associated with sunburn were age and socioeconomic factors. Sunburn
      prevalence was greatest in respondents 18 to 24 years old (61%). This group was
      more likely to have a sunburn than respondents 45 to 54 years of age (odds ratio
      [OR] = 2.76). Higher income and higher levels of education were positively
      associated with sunburn (OR 1.67 and 1.63, respectively). Individuals reporting
      recent binge drinking had a higher prevalence of sunburn (OR = 1.33).
      LIMITATIONS: The Behavioral Risk Factor Surveillance System does not include data
      on skin type or sun protection behavior; therefore the impact of these factors
      was not assessed. CONCLUSION: Sunburn occurs at a very high rate in the United
      States.

PMID- 17010736
TI  - Alcohol consumption and self-reported sunburn: a cross-sectional, population
      based survey.
AB  - BACKGROUND: Heavy drinking has been associated with several cancers, including
      melanoma and basal cell carcinoma. OBJECTIVE: The purpose of this study was to
      determine whether excessive drinking is associated with sunburn, a risk factor
      for skin cancer. METHODS: As part of the 2004 Behavioral Risk Factor Surveillance
      System, a population-based telephone survey, 299,658 adults reported their use of
      alcohol in the preceding month and a history of sunburn in the preceding year.
      RESULTS: Approximately 33.5% of respondents reported a sunburn within the past
      year. Heavier average alcohol use and binge drinking were both positively
      associated with prevalence and number of sunburns within the past year. The
      adjusted odds ratios for prevalence and number of sunburns among binge drinkers
      were 1.39 (95% confidence interval 1.31-1.48) and 1.29 (95% confidence interval,
      1.20-1.38), respectively. Associations tended to be of similar magnitude for
      average alcohol use and in all subgroups evaluated. LIMITATIONS: This study was
      cross-sectional and relied upon participant self-report. CONCLUSION: Excessive
      drinking is associated with higher rates of sunburn among American adults. The
      observed relationship typifies the high-risk behavior associated with excessive
      drinking and suggests one pathway linking alcohol use with skin cancer.

PMID- 17010737
TI  - Etanercept induces apoptosis of dermal dendritic cells in psoriatic plaques of
      responding patients.
AB  - BACKGROUND: Etanercept is a tumor necrosis factor-alpha binding fusion protein
      that demonstrates efficacy in the treatment of psoriasis, which is accompanied by
      decreased plaque infiltration of T cells and myeloid dendritic cells. We
      hypothesized that etanercept decreases inflammatory cell infiltration by inducing
      apoptosis. OBJECTIVE: We sought to investigate the effect of etanercept on
      circulating and plaque leukocyte apoptosis in psoriasis. METHODS: Blood and
      plaque specimens were obtained from 10 patients with psoriasis treated with
      etanercept (25 mg subcutaneously twice weekly) for 24 weeks. Apoptosis was
      determined in tissue samples using immunohistochemistry and flow cytometry.
      RESULTS: Etanercept selectively induced apoptosis in dermal dendritic cells in
      plaques of responding patients at 1 month, before most of the clinical and
      histologic response was achieved. No apoptosis was detected in plaque or
      circulating T cells or in circulating monocytes. LIMITATIONS: Addition of
      multiple time points earlier than 1 month would be valuable to establish the time
      point of maximum induction in cell apoptosis. CONCLUSION: Etanercept selectively
      induces apoptosis of pathogenic dermal dendritic cells in responding patients
      early in the course of treatment.

PMID- 17010738
TI  - Clinical response to adalimumab treatment in patients with moderate to severe
      psoriasis: double-blind, randomized controlled trial and open-label extension
      study.
AB  - BACKGROUND: Tumor necrosis factor is pivotal in the pathogenesis of psoriasis.
      Adalimumab is a fully human monoclonal immunoglobulin G1 antibody that
      neutralizes tumor necrosis factor. OBJECTIVES: We sought to assess the efficacy
      and safety of adalimumab in patients with moderate to severe plaque psoriasis.
      METHODS: In this multicenter, randomized, double-blind, placebo-controlled study,
      147 patients received adalimumab (40 mg every other week or 40 mg/wk) or placebo.
      After 12 weeks of blinded therapy, patients taking adalimumab could continue
      their assigned dosages in a 48-week extension trial; patients taking placebo were
      switched to adalimumab (40 mg every other week). RESULTS: At week 12, 53% of
      patients taking adalimumab every other week, 80% of patients taking adalimumab
      weekly, and 4% of patients taking placebo achieved 75% improvement in Psoriasis
      Area and Severity Index score (P < .001). Responses were sustained for 60 weeks.
      No new safety signals were noted compared with the existing adalimumab clinical
      safety database. LIMITATIONS: The study was insufficiently powered to detect rare
      adverse events associated with adalimumab. CONCLUSIONS: Adalimumab significantly
      improved psoriasis and was well tolerated for 60 weeks.

PMID- 17010739
TI  - Determining the relative importance of patient motivations for nonadherence to
      topical corticosteroid therapy in psoriasis.
AB  - BACKGROUND: Medication nonadherence is a significant problem in psoriasis.
      Although previous research has aimed to quantify the prevalence of nonadherence
      in topical medication users, patient motivations for intentional nonadherence are
      not fully understood. OBJECTIVE: Our purpose was to determine the relative
      importance of factors contributing to nonadherence in topical corticosteroid
      users with psoriasis. METHODS: A survey was distributed to psoriasis patients
      visiting an outpatient clinic. RESULTS: Among the 53 persons surveyed, medication
      nonadherence was 40%. Frustration with medication efficacy, inconvenience, and
      fear of side effects were the most important reasons patients deviated from usage
      instructions. Subjects who did not receive instructions on topical treatment
      duration used corticosteroids longer (>8 weeks) than subjects who were instructed
      (P < .05). LIMITATIONS: A relatively small sample size prevented trends in
      demographic predictors of adherence from reaching statistical significance. The
      patient self-report format has the potential to introduce recall bias.
      CONCLUSIONS: Factors contributing to intentional nonadherence, including
      dissatisfaction with efficacy, inconvenience, and fear of side effects, are the
      most important patient-identified barriers to appropriate use of topical steroids
      in psoriasis. Clear patient instructions on the intended steroid treatment
      duration may reduce adverse effects from overuse.

PMID- 17010740
TI  - Orbit and eyelid hemangiomas: is there a relationship between location and ocular
      problems?
AB  - PURPOSE: Infantile hemangiomas of the orbit and eyelid can cause serious ocular
      problems, such as astigmatism and amblyopia. Magnetic resonance imaging and
      ultrasonography are the best ways to establish the diagnosis and to evaluate the
      extent of the lesion. Our goal was to correlate the lesion location with the
      visual impairment. MATERIAL AND METHODS: This was a retrospective study (1992
      2004) of 63 cases of orbit and eyelid hemangiomas (13 male, 50 female patients;
      ages: 1 day old to 3 years old). Imaging methods were magnetic resonance imaging
      or computed tomographic-scanning and color Doppler ultrasonography. The anatomic
      definition was palpebral, extraconal, and extraconal with intraconal involvement.
      All patients had ophthalmologic evaluations. RESULTS: The hemangiomas were
      palpebral (n = 32) (normal vision: 19; amblyopia and/or astigmatism: 13),
      extraconal, and extraconal with intraconal involvement (n = 31) (normal vision:
      4; amblyopia and/or astigmatism: 27). LIMITATIONS: This study was small; a
      prospective study is needed. CONCLUSION: Orbit and eyelid hemangiomas need to be
      carefully evaluated by an ophthalmologist. Extraconal and intraconal hemangiomas
      are more frequently associated with ocular involvement. However, ocular
      complications can occur in palpebral lesions.

PMID- 17010741
TI  - Cost-effectiveness of diagnostic tests for toenail onychomycosis: a repeated
      measure, single-blinded, cross-sectional evaluation of 7 diagnostic tests.
AB  - OBJECTIVE: Our purpose was to estimate and compare the cost-effectiveness of the
      most commonly used diagnostic tests for onychomycosis: potassium hydroxide
      preparation (KOH), interpreted both by a dermatologist (KOH-CLINIC) and a
      laboratory technician (KOH-LAB); KOH with dimethyl sulfoxide (KOH-DMSO) and with
      chlorazol black E (KOH-CBE), interpreted by a dermatologist; culture using
      dermatophyte test medium, culture with Mycobiotic and Inhibitory Mold Agar (Cx);
      and histopathologic analysis using periodic acid-Schiff stain (PAS). METHODS:
      This was a repeated-measure, blinded, cross-sectional study conducted at the
      Minneapolis Veterans Affairs Medical Center. Inclusion criteria included: at
      least one toenail with 25% or more clinical disease, which was defined as
      subungual debris with onycholysis and/or onychauxis. Exclusion criteria included
      other nail dystrophies, use of oral antifungal medication for 2 months or longer
      within the past year, or topical ciclopirox lacquer within 6 weeks of enrollment.
      The main outcome measure was the cost-effectiveness (Medicare and non-Medicare
      costs) of 7 diagnostic tests. Sensitivity (at least 3 positive tests) was the
      unit of effectiveness. RESULTS: Two hundred four participants were enrolled;
      their average age was 69.5 years and 95.5% were male. PAS was the most sensitive
      test (98.8%); it was statistically significantly more sensitive than all other
      diagnostic tests except KOH-CBE (94.3%). Dermatophye test medium was the least
      sensitive test (57.3%). KOH-CBE was statistically significantly more cost
      effective than any other test, with the exception of KOH-CLINIC and KOH-LAB. PAS
      was the least cost effective. LIMITATIONS: Test specificities were not evaluated.
      CONCLUSION: KOH-CBE should be the test of choice for practitioners confident in
      interpreting KOH preparations because of its combination of high sensitivity and
      cost-effectiveness.

PMID- 17010742
TI  - Randomized, double-blind comparison of 1 mg/L versus 5 mg/L methoxsalen bath-PUVA
      therapy for chronic plaque-type psoriasis.
AB  - BACKGROUND: Bath-psoralen plus ultraviolet A (PUVA) radiation therapy is
      increasingly replacing oral PUVA because of its superior short- and long-term
      safety profile. Several investigations in recent years have led to a refinement
      of the bath-PUVA protocol; however, the optimal therapeutic concentration of
      methoxsalen in the bath water has as yet not been delineated. OBJECTIVES: The
      therapeutic efficacy and tolerability of bath-PUVA by using two different
      dilutions of methoxsalen (1 mg/L vs 5 mg/L or 0.0001% vs 0.0005%) were compared
      in 46 patients with chronic plaque-type psoriasis in a prospective, randomized,
      double-blind study. METHODS: Scores of the Psoriasis Area and Severity Index
      excluding psoriasis of the head (PASI(TUL)) and the Plaque Severity Index (PSI)
      were assessed at baseline and at biweekly intervals thereafter until
      (near)complete clearance or maximal improvement. In addition, methoxsalen plasma
      levels were determined immediately after the psoralen bath during the first week
      of treatment and treatment-related side effects were recorded throughout the
      entire study period. RESULTS: The median baseline PASI(TUL) score decreased from
      11.7 (7.5-32.8) to 3.3 (0.6-1.2) (-72%) in the 1 mg/L methoxsalen group and from
      10.8 (6.6-20.7) to 1.4 (03.2) (-87%) in the 5 mg/L methoxsalen group (P < .01).
      The median baseline PSI score decreased from 9 (6-12) to 3.1 (0.6-10) (-66%) in
      the 1 mg/L methoxsalen group and from 9.3 (7.3-12) to 1.6 (0-3.6) (-83%) in the 5
      mg/L methoxsalen group (P < .01). The median cumulative UVA exposure dose was
      25.4 (5.3-81.5) J/cm2 for 5 mg/L methoxsalen and 71.9 (20.7-587.3) J/cm2 for 1
      mg/L methoxsalen (P = .001). The number of exposures (22 [11-29] vs 23 [11-34])
      and treatment duration (43 [19-68] vs 44 [23-66] days) was comparable for both
      methoxsalen dilutions (P = .97). Median psoralen plasma levels were 0 (0-26)
      ng/mL after the 1 mg/L and 30 (0-64) ng/mL after the 5 mg/L methoxsalen immersion
      (P = .001). Mild to moderate adverse events were more common in the 5 mg/L
      methoxsalen group. LIMITATIONS: The conclusions of this randomized controlled
      study are limited by the relatively small sample size. CONCLUSIONS: Our data
      indicate that in bath-PUVA treatment the use of a high (5 mg/L) methoxsalen
      concentration is substantially more effective in clearing chronic plaque-type
      psoriasis than a low (1 mg/L) concentration.

PMID- 17010743
TI  - The use of methotrexate alone or in combination with low doses of oral
      corticosteroids in the treatment of alopecia totalis or universalis.
AB  - Treatment of severe alopecia areata (AA) remains difficult. To assess the
      tolerance and efficacy of methotrexate (MTX) in the treatment of severe long-term
      AA, we retrospectively evaluated 22 patients with AA totalis or universalis with
      a mean duration of 11.0 +/- 8.8 years who were treated with MTX either alone (n =
      6) or associated with low doses of oral prednisone (n = 16). MTX was given at an
      initial weekly dosage of 15 mg (n = 3), 20 mg (n = 9), or 25 mg (n = 10). Oral
      prednisone was given at an initial dosage of 10 mg/d in one patient and 20 mg/d
      in 15 patients. In all, 14 patients (64%) achieved a total recovery including 3
      of 6 patients treated by MTX alone and 11 of 16 who had received the combined
      treatment. Of the 14 patients who had total hair regrowth, 6 stopped MTX. In all,
      3 patients maintained hair regrowth and 3 relapsed. Retreatment of these 3
      patients by MTX resulted again in hair regrowth. No severe side effect was
      observed. Although limited by its uncontrolled character, this study shows that
      MTX and low doses of oral corticosteroids may be an effective and well-tolerated
      treatment for severe types of AA.

PMID- 17010744
TI  - A randomized, multicenter study of calcipotriene ointment and clobetasol
      propionate foam in the sequential treatment of localized plaque-type psoriasis:
      short- and long-term outcomes.
AB  - BACKGROUND: The merit of topical sequential therapy involving clobetasol foam and
      calcipotriene ointment has not been experimentally demonstrated. OBJECTIVE: We
      sought to assess the short-term efficacy of twice-daily clobetasol foam plus
      calcipotriene ointment compared with either agent alone as monotherapy and to
      compare long-term use of weekday calcipotriene ointment with or without
      clobetasol foam weekend pulse therapy. METHODS: Eighty-six subjects with plaque
      type psoriasis received twice-daily treatment with clobetasol foam plus
      calcipotriene ointment or either agent as monotherapy for 2 weeks. Subjects in
      the combination group who achieved remission received weekday calcipotriene plus
      weekend pulse therapy with either clobetasol foam or vehicle for 6 months.
      RESULTS: After 2 weeks, psoriasis scores were significantly lower (P < .001) in
      the combination therapy group (adjusted trunk lesion score = 0.67) compared with
      monotherapy with either agent (lesion scores = 1.40 calcipotriene, 1.13
      clobetasol foam). During the follow-up "weekday-weekend" phase, after 6 months,
      weekend pulse clobetasol foam was associated with a trend toward greater
      maintenance of remission compared with vehicle (92% improvement of trunk lesion
      vs 62%). LIMITATIONS: Small sample size may have hampered the detection of
      statistical significance during long-term therapy. CONCLUSION: The combination of
      clobetasol foam and calcipotriene ointment is significantly more effective than
      monotherapy for short-term treatment. Weekday calcipotriene plus weekend pulse
      clobetasol foam shows a consistent trend toward greater maintenance of remission.

PMID- 17010745
TI  - Acute graft-versus-host disease after liver transplantation diagnosed by
      fluorescent in situ hybridization testing of skin biopsy specimens.
AB  - Acute graft-versus-host disease after orthotopic liver transplantation is an
      underrecognized entity with a guarded prognosis. We describe a patient who
      underwent orthotopic liver transplantation with an HLA-matched donor liver. She
      had an uneventful recovery from operation up until day 36 posttransplantation,
      when she developed a generalized, erythematous, mostly macular eruption,
      accompanied by ascites, diarrhea, and fever. The diagnosis of graft-versus-host
      disease was considered but a drug rash could not be excluded. A polymerase chain
      reaction-based chimerism assay failed to identify donor DNA in peripheral blood.
      A confirmatory fluorescent in situ hybridization analysis revealed significant
      numbers of donor lymphocytes in biopsied skin, with lesser amounts in biopsy
      specimens from the stomach and colon. Despite immunosuppressive treatment, the
      patient died of overwhelming sepsis 18 weeks after transplantation. We conclude
      that early testing of skin biopsy specimens using fluorescent in situ
      hybridization in sex-mismatched patients with orthotopic liver transplantation
      can serve as an early diagnostic tool for graft-versus-host disease.

PMID- 17010746
TI  - Acquired ichthyosis.
AB  - Acquired ichthyosis (AI) is a nonhereditary cutaneous disorder characterized by
      dry, rough skin with prominent scaling that involves significant portions of the
      body. It has been associated with malignancies; autoimmune/inflammatory,
      metabolic, endocrine, and infectious diseases; and medication use. Most
      microscopic studies of AI exhibit hyperkeratosis with a reduced or absent
      granular layer. Because AI has been linked to a variety of conditions, the workup
      of a patient presenting with this finding can be complex. We present an update on
      AI to provide clinicians with direction regarding the assessment and treatment of
      patients presenting with AI. An algorithm for the evaluation of patients
      presenting with AI is provided.

PMID- 17010747
TI  - Dermatologic side effects associated with the epidermal growth factor receptor
      inhibitors.
AB  - Epidermal growth factor receptor (EGFR) inhibitors are associated with unique and
      dramatic dermatologic side effects. Cetuximab, erlotinib, and gefitinib have been
      approved for patients with colorectal and non-small cell lung cancer refractory
      or intolerant to chemotherapy. Our aim was to describe key clinical features of
      common dermatologic adverse reactions among EGFR inhibitors, focusing mainly on
      skin toxicity, as well as to discuss the pathology, possible causes, and
      suggested treatments for these reactions. The most commonly encountered adverse
      effect was a mild skin toxicity characterized by a sterile follicular and
      pustular rash that may be treated empirically and usually does not require
      treatment modification. Although the precise mechanism for development of rash is
      not well defined, it is related to inhibition of EGFR-signaling pathways in the
      skin, and may serve as visible markers of anti-tumor activity and therapeutic
      efficacy. Secondary adverse reactions seen with anti-EGFR therapy include
      xerosis, pruritus, paronychia, hair abnormality, and mucositis.

PMID- 17010748
TI  - Infantile hemangiomas.

PMID- 17010749
TI  - Multiple painful cutaneous nodules and renal mass.

PMID- 17010750
TI  - Disparities in dermatology educational resources.
AB  - Patients with dark skin can present with morphologic variants, subtle disease
      presentations, and disease manifestations requiring unique management and
      therapies. With African Americans, Asians, and Hispanic Americans becoming a
      significant portion of the population, dermatologists must be able to diagnose
      and manage skin conditions in people of color. In this study, core dermatology
      educational sources were examined to determine if they provide dermatologists and
      trainees with the knowledge base necessary to diagnose and treat skin disease in
      the ethnic patient. Overall, the coverage of dark skin at national meetings and
      in photographs in the major dermatology resources is limited and variable. More
      consistent photographic coverage and textual information describing common and
      serious skin diseases in people of color should be incorporated into educational
      resources.

PMID- 17010751
TI  - Toll-like receptors in acne vulgaris.

PMID- 17010752
TI  - Surgical pearl: a novel technique for repair of broken running cutaneous sutures.

PMID- 17010753
TI  - Surgical pearl: antifog solution for surgery goggles.

PMID- 17010754
TI  - The acanthosis nigricans form of epidermal nevus.
AB  - We observed 4 individuals with the acanthosis nigricans (AN) form of epidermal
      nevus, with clinical and histopathologic features of AN oriented along Blaschko's
      lines. Three patients had stable lesions since childhood. One patient
      concurrently had typical bilateral AN lesions. This condition may represent a
      mosaic form of AN.

PMID- 17010755
TI  - Dual diagnosis of pemphigus vulgaris and connective tissue disease.
AB  - This is a retrospective analysis of patients with pemphigus vulgaris and
      connective tissue disease (CTD) present as systemic lupus erythematosus, mixed
      CTD, or both. Pemphigus vulgaris was severe, difficult to treat, but eventually
      responded to therapy, resulting in a remission. In 6 patients, the CTD was stable
      and controlled with symptomatic therapy, and in 7 patients required systemic
      therapy. Life-threatening systemic involvement in systemic lupus erythematosus or
      mixed CTD-such as renal, cardiac, and neurologic-were absent in these patients on
      8 years (range 3-18 years) of follow-up. There are two limitations to this study.
      First, it is a retrospective study. Second, no other disease control groups were
      used for comparison purposes.

PMID- 17010756
TI  - Cyclosporine in chronic idiopathic urticaria: a double-blind, randomized, placebo
      controlled trial.
AB  - BACKGROUND: Treatment of severe recalcitrant chronic idiopathic urticaria (CIU)
      is difficult. OBJECTIVE: To assess the efficacy and safety of oral cyclosporin A
      (CsA) in CIU. METHODS: The response to CsA was evaluated in 99 CIU patients with
      a double-blind, randomized, three-armed study: 16-week CsA, 8-week CsA +8-week
      placebo, and 16-week placebo. All patients received cetirizine throughout the
      study period and were followed-up after 8 weeks. RESULTS: Fewer therapeutic
      failures occurred with 16-week CsA (n = 3) than with placebo (n = 11) and 8-week
      CsA (n = 8). After 8 and 16 weeks, symptom scores significantly improved in both
      CsA groups over with placebo. Two patients discontinued because of hypertension.
      LIMITATIONS: During the study period, CsA was not administered at a constant
      dose; from day 28 the daily dose was 3 mg/kg, which is likely to be less
      effective and better tolerated than higher dosages. CONCLUSION: CsA in addition
      to background therapy with cetirizine may be useful in the treatment of CIU.

PMID- 17010757
TI  - Treatment of gefitinib-associated folliculitis.
AB  - Gefitinib (Iressa), an epidermal growth factor inhibitor approved for treatment
      of advanced nonsmall cell lung carcinoma, is associated with an acneiform
      distributed folliculitis. Treatment attempts for this folliculitis have been
      noted in the literature, but photodocumentation of results has not been reported.
      We report 3 consecutive cases of gefitinib-associated folliculitis with
      photodocumentation of their treatment responses to combination therapy with
      topical metronidazole and oral tetracyclines.

PMID- 17010758
TI  - Borderline tuberculoid leprosy in a woman from the state of Georgia with
      armadillo exposure.
AB  - In the southern and southeastern United States, the 9-banded armadillo is an
      important reservoir for Mycobacterium leprae, the causative agent of leprosy
      (Hansen's disease). Here, we describe a woman living in Georgia with borderline
      tuberculoid leprosy who worked for many years in a garden where armadillos
      burrowed or were buried. There was no history of foreign travel or known exposure
      to a person with leprosy. Treatment with 6 once-monthly combined doses of
      rifampin, ofloxacin, and minocycline was successful.

PMID- 17010759
TI  - Granulomatous reaction to titanium alloy: an unusual reaction to ear piercing.
AB  - A 68-year-old man presented with 4 firm, flesh-colored, and slightly erythematous
      nodules located on the superior pole and lobule of each ear. Although reluctant
      to provide details, it was discovered he had pierced his ears approximately 10
      years earlier, and the nodules developed at the sites of the piercings. Keloids
      were suggested clinically and the lesions were excised. Microscopic examination
      demonstrated epithelialized tracts surrounded by a granulomatous infiltrate of
      macrophages, lymphocytes, and plasma cells. Closer examination revealed minute
      brown-black particles within macrophages. Dark-field microscopy confirmed the
      metallic nature of the particles. Environmental scanning electron microscopy with
      energy dispersive spectroscopy revealed the particles to be composed of titanium,
      aluminum, and vanadium. It would appear that in rare circumstances titanium alloy
      used in body piercing may engender a granulomatous dermatitis. The rarity of such
      a response to titanium alloy is discussed and the literature appraised.

PMID- 17010760
TI  - Dermatology-related postmarketing study commitments to the Food and Drug
      Administration.

PMID- 17010761
TI  - Dolphin-to-human transmission of lobomycosis?

PMID- 17010762
TI  - Is popular cellulites a worse dermatosis than remembered itch?

PMID- 17010764
TI  - Ocular involvement in pemphigus vulgaris.

PMID- 17010765
TI  - Case of fatal cutaneous mucinous carcinoma of the scalp with multiple in-transit
      and pulmonary metastases unlikely to have been of primary cutaneous origin.

PMID- 17010766
TI  - Hypogammaglobulinemia as an early sign of drug-induced hypersensitivity syndrome.

PMID- 17010767
TI  - Dermatoscopy, not dermoscopy!

PMID- 17010770
TI  - 25 Years of HIV/AIDS: a dermatologist epidemic watcher's perspective.
AB  - Though history will mark June 1981 as the birthday of the AIDS pandemic, the
      first true case of the syndrome and its cause originated years before in West
      Central Africa. History also highlights the irony that the discovery of AIDS, the
      detection of its cause, and the development of drugs for its treatment, all
      occurred far from its origin, and now, 25 years later, the greatest burden of
      this disease is where it is believed to have started.

PMID- 17010768
TI  - The clinical and histologic spectrum of chronic graft-versus-host disease.

PMID- 17010771
TI  - The global epidemiology of HIV/AIDS.
AB  - HIV infected nearly 5 million and killed more than 3 million people in 2005.
      Whereas traditional epidemics have been limited to high-risk populations, in many
      regions, it has generalized to the at-large population, with heterosexual sex
      being the predominant source of transmission. The virus has hit sub-Saharan
      Africa the hardest, although major epidemics are now transpiring in Asia, Eastern
      Europe, and the Caribbean. The United Nations and World Health Organization have
      produced targeted prevention strategies to control the pandemic that focus on
      comprehensive prevention activities and universal access to care.

PMID- 17010772
TI  - HIV/AIDS in sub-Saharan Africa.
AB  - The impact that HIV/AIDS has made on modern society is unquestionable. It has
      ravaged societies across the globe without the discrimination. It has swept
      across the globe like no other plague in human history, leaving nothing in its
      path untouched. Like all catastrophes, the havoc wreaked by HIV/AIDS most impacts
      people living in the poorest nations of the world. This article deals with the
      impact of HIV/AIDS in sub-Saharan Africa.

PMID- 17010773
TI  - Acute retroviral syndrome.
AB  - The acute retroviral syndrome (ARS), also known as primary HIV infection, acute
      HIV infection, and HIV seroconversion syndrome, is the earliest clinical
      manifestation of HIV infection. Early detection of HIV allows for medical and
      behavioral interventions critical to the management of HIV. This article reviews
      the clinical features and current management of individuals with ARS.

PMID- 17010774
TI  - Inflammatory noninfectious dermatoses of HIV.
AB  - Since the advent of HIV/AIDS, a variety of inflammatory noninfectious skin
      conditions have been described in HIV-infected patients. This review will discuss
      a group of inflammatory, noninfectious dermatoses that, although not exclusive to
      HIV/AIDS, are commonly observed in HIV-infected patients and pose an apparent
      paradox in a disease that supposedly involves suppression of cellular immunity.

PMID- 17010775
TI  - Pruritic papular eruption in HIV.
AB  - Pruritic papular eruption (PPE) is characterized chronic pruritus and symmetric
      papular eruptions on the trunk and extremities with the absence of other
      definable causes of itching in an HIV-infected patient. PPE seems to be much more
      prevalent in less developed regions of the world. The etiology of this
      distressing condition is unclear, although an inappropriate response to an
      exogenous agent, such as arthropod bites, may underlie the pathogenesis.
      Identifying PPE's association with the immune dysregulation of HIV and
      distinguishing this condition from other pruritic disorders found in HIV-infected
      patients is important for optimal management.

PMID- 17010776
TI  - Adverse cutaneous drug eruptions and HIV: a clinician's global perspective.
AB  - Adverse drug reactions (ADRs) are common and mostly avoidable. Some ADRs cannot
      as yet be predicted, but at-risk populations/patients and high-risk drugs are
      identifiable. HIV-infected patients are at risk of developing cutaneous ADRs,
      especially Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug
      hypersensitivity syndrome. Multiple factors of causation variably present in
      patients with HIV infection best explain the pathogenesis of these cutaneous
      ADRs. When no effective alternate therapy is available, drug rechallenge in HIV
      infected patients can be attempted with little morbidity or mortality if done
      according to rationalized protocols.

PMID- 17010777
TI  - Cutaneous infections associated with HIV/AIDS.
AB  - With diminished and dysregulated cell-mediated immunity, HIV-infected individuals
      are susceptible to a myriad of skin infections. These infections include the
      conditions encountered in immunocompetent patients, as well as infections seen
      almost exclusively in the setting of HIV infection. The HIV/AIDS pandemic has
      made some previously rare infections more prominent. Although antiretroviral
      therapy has been helpful in relieving the burden of cutaneous infections in HIV
      infected patients, it does not prevent all opportunistic infections in the skin
      and also has created new dilemmas.

PMID- 17010778
TI  - Syphilis and HIV infection: an update.
AB  - Although once on decline in the United States and Europe, the incidence of
      syphilis has been on the rise since 2000. This increase is noteworthy because
      there is a high coinfection rate with HIV, especially among men who have sex with
      men. In light of high coinfection rates, all HIV-infected patients should be
      tested for syphilis and vice versa. HIV can alter the clinical manifestations of
      syphilis and, in turn, syphilis has the potential to change the course and
      transmission of HIV. This article addresses variations in clinical presentation,
      diagnosis, and management of individuals coinfected with HIV and syphilis.

PMID- 17010779
TI  - HIV-associated Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is a multifocal vascular tumor that occurs most commonly in
      patients who have immunosuppression caused by HIV. KS-associated herpes virus
      (human herpes virus 8, KSHV) has been identified as the causative agent. There
      are marked geographic differences in the prevalence of both KS and seropositivity
      to KSHV. The incidence of the tumor has shown a marked decline in first-world
      countries with the widespread use of effective antiretroviral therapy. The most
      effective anthracycline is pegylated liposomal doxorubicin; however, few
      developing countries, where KS prevalence is highest, can afford to use these
      agents.

PMID- 17010780
TI  - HIV and skin cancer.
AB  - AIDS produces profound alterations in normal immunity. Impaired cellular immunity
      permits new tumor formation as evidenced by the solid-organ transplant
      literature. The weakened cellular immune system of HIV-infected patients
      resembles in some ways the iatrogenic immunosuppression in solid-organ transplant
      recipients. This article summarizes what is known about skin cancer in the solid
      organ transplant population and compares the immunodysregulation of HIV infection
      with the iatrogenic immunosuppression following solid-organ transplantation.

PMID- 17010781
TI  - Pediatric HIV/AIDS and the skin: an update.
AB  - In 2005 there were 2.1 million children under the age of 15 years living with HIV
      in sub-Saharan Africa. As in the adult pandemic, attendant skin disease is
      prevalent in children. This article provides an update of pediatric HIV/AIDS and
      its cutaneous manifestations from four main aspects: epidemiology, skin disease
      as an indicator of immune status, immune reconstitution inflammatory syndrome,
      and the impact of antiretroviral agents on skin disease.

PMID- 17010782
TI  - Antiretroviral therapy: a primer for dermatologists.
AB  - Combination antiretroviral therapy (ART) has transformed the care of individuals
      who have HIV infection. Effective ART has resulted in dramatic reductions in
      mortality, hospitalization rates, and the development of AIDS-defining illnesses.
      This article discusses the variety of agents that can comprise an effective ART
      regimen, focusing on the basic principles of ART, the indications for initiating
      ART in treatment-naive individuals who have established HIV infection, and the
      challenges associated with the use of antiretroviral medications.

PMID- 17010783
TI  - Dermatologic manifestations of the immune reconstitution inflammatory syndrome.
AB  - The immune reconstitution inflammatory syndrome (IRIS) represents a diverse range
      of immunopathologic reactions resulting in clinical deterioration that may occur
      as immune function is partially restored in HIV-infected patients receiving
      highly active antiretroviral therapy. Approximately half of IRIS events are
      dermatologic, and dermatologic IRIS is described in relation to a wide range of
      conditions, the commonest being herpes zoster and herpes simplex. Most cases of
      IRIS result in mild and moderate symptoms, but non-dermatologic manifestations
      related to IRIS have resulted in death. This article covers certain general
      issues related to IRIS and then focuses on the spectrum of dermatologic
      manifestations.

PMID- 17010784
TI  - Redefining heart failure: the utility of genomics.
AB  - In this era of genomics, new technologies and the information that they generate
      have a wide range of potential applications to heart failure. Though there has
      not been widespread practical use of genomic information in everyday practice,
      there are many examples of how this information is beginning to transform the way
      we look at disease states in terms of diagnosis, prognosis, and treatment. The
      experience of oncology and other fields helps inform the heart failure field of
      not only the use of this information in investigating diagnosis, prognosis, and
      treatment response, but the reciprocal nature of this information. This
      information can be clinically useful (for instance, predicting treatment
      response) as well as further drive laboratory investigation (teasing out the
      biological pathways in non-responders to treatment can be a focus of new drug
      discovery); this is the essence of translational medicine. We believe that this
      is a good time to review where new technologies and information they generate can
      be placed into our classic understanding of heart failure: that is how we might
      redefine cardiomyopathy given our new information. Here we will review genomic
      evidence to date and how it can and may be considered in the evaluation and
      management of cardiomyopathies.

PMID- 17010785
TI  - A proposal for an advanced cardiovascular imaging training track.
AB  - Cardiovascular (CV) imaging has experienced major growth and technological
      advances with respect to the long-standing traditional cardiac imaging procedures
      of echocardiography and nuclear cardiology, the emergence of cardiac computed
      tomography and magnetic resonance imaging in clinical practice, and multimodality
      and molecular imaging as new technologies. Therefore, it is perhaps timely to
      change the training paradigm for fellows interested in emphasizing CV imaging as
      a subspecialty in their professional careers and desiring extensive training in
      all CV imaging modalities. Proposed is the establishment of a formal fourth year
      of training leading to board certification in advanced CV imaging. Areas of
      training would include the acquisition of knowledge of physics and
      instrumentation related to the various imaging modalities, interpretation and
      quantitation of imaging variables, multimodality imaging technology, molecular
      and vascular imaging, and clinical guidelines with appropriateness criteria for
      all technologies. The training track would lead to an American Board of Internal
      Medicine examination for a Certificate of Added Qualification, similar to that
      for subspecialization in electrophysiology and interventional cardiology, with
      noninvasive cardiologists who have already completed fellowship training given
      the opportunity to sit for an examination on the basis of predetermined
      eligibility criteria. One benefit of this CV imaging subspecialty track that
      provides cardiologists with expertise in all imaging modalities is the capability
      to select the best modality for the clinical indication and to independently
      interpret multimodality imaging studies. Its rigorous didactic and procedural
      requirements would enhance quality of CV imaging, enhance research, and increase
      the speed with which new discoveries are translated into practice. This
      ultimately would yield better patient outcomes.

PMID- 17010786
TI  - Vessel size and outcome after coronary drug-eluting stent placement: results from
      a large cohort of patients treated with sirolimus- or paclitaxel-eluting stents.
AB  - OBJECTIVES: This study sought to investigate the influence of vessel size on the
      outcomes of patients after drug-eluting stent (DES) implantation. BACKGROUND:
      There are no dedicated studies on the influence of vessel size on the outcomes of
      patients treated with different DES. METHODS: The study population was composed
      of 2,058 consecutive patients who received sirolimus-eluting stents (SES) or
      paclitaxel-eluting stents (PES). Patients were grouped into tertiles according to
      vessel size (<2.41 mm in the lower tertile, 2.41 to 2.84 mm in the middle
      tertile, and >2.84 mm in the upper tertile). The primary end point was target
      lesion revascularization (TLR). Secondary end points were binary angiographic
      restenosis and the composite of death or myocardial infarction. RESULTS: Vessel
      size did not influence the composite end point of death and myocardial
      infarction. The TLR rates were higher among patients in the lower tertile (12.1%)
      as compared with the middle (8.4%) and upper (8.0%) tertiles (p = 0.02). In a
      multivariate analysis, vessel size emerged an independent predictor of TLR (p =
      0.009). The model showed also a significant interaction between DES type and
      vessel size regarding TLR (p = 0.008). There was a significant difference in TLR
      rates among patients treated with SESs (8.6%) and PESs (16.4%) in the lower
      tertile (p = 0.002), but not in the middle and upper tertiles. CONCLUSIONS: The
      influence of vessel size on restenosis is related to the specific DES used, with
      SESs providing better outcomes than PESs in small but not in large coronary
      vessels.

PMID- 17010787
TI  - All drug-eluting stents are equal, but some drug-eluting stents are more equal
      than others.

PMID- 17010788
TI  - Clinical outcomes for sirolimus-eluting stents and polymer-coated paclitaxel
      eluting stents in daily practice: results from a large multicenter registry.
AB  - OBJECTIVES: We compared the clinical outcome of sirolimus-eluting stents (SES)
      and paclitaxel-eluting stents (PES) in a real-world scenario. BACKGROUND: In
      selected patients, SES has been associated with lower late luminal loss than PES.
      Whether this emerging biological difference could translate into different
      clinical efficacy in daily practice is presently unknown. METHODS: This analysis
      included 1,676 consecutive patients with de novo coronary lesions treated solely
      with drug-eluting stents (SES = 992; PES = 684). All patients were enrolled in a
      dynamic prospective registry comprising 13 hospitals. We assessed the cumulative
      incidence of major adverse cardiac events (MACE), defined as death, myocardial
      infarction (MI), and target vessel revascularization (TVR) during follow-up.
      RESULTS: Overall, 29% of the patients had diabetes, 23% had prior MI, and 9% had
      poor left ventricular function. ST-segment elevation MI was diagnosed at
      admission in 12%. Multivessel intervention was performed in 16%. At 1-year follow
      up, SES was associated with a reduced incidence of MACE (9.2% SES vs. 14.1% PES;
      p = 0.007) and TVR (5.0% SES vs. 10.0% PES; p = 0.0008) compared to PES. A
      propensity analysis with many clinical and angiographic variables was carried out
      to adjust for baseline differences. In this analysis, SES was associated with a
      44% risk reduction of MACE (hazard ratio 0.56, 95% confidence interval 0.39 to
      0.78) and a 55% reduction of TVR (hazard ratio 0.45, 95% confidence interval 0.29
      to 0.70). This result was consistent across most subgroups tested. Similar rates
      of death and MI were observed in the 2 treatment groups. CONCLUSIONS: In this
      large real-world population, SES improved 1-year clinical results as compared to
      PES.

PMID- 17010789
TI  - Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of
      contemporary randomized clinical trials.
AB  - OBJECTIVES: This study sought to systematically determine whether early invasive
      therapy improves survival and reduces adverse cardiovascular events in the
      management of non-ST-segment elevation acute coronary syndromes. BACKGROUND:
      Although early invasive therapy reduces recurrent unstable angina, the magnitude
      of benefit on other important adverse outcomes is unknown. METHODS: Clinical
      trials that randomized non-ST-segment elevation acute coronary syndrome patients
      to early invasive therapy versus a more conservative approach were included for
      analysis. RESULTS: In all there were 7 trials with 8,375 patients available for
      analysis. At a mean follow-up of 2 years, the incidence of all-cause mortality
      was 4.9% in the early invasive group, compared with 6.5% in the conservative
      group (risk ratio [RR] = 0.75, 95% confidence interval [CI] 0.63 to 0.90, p =
      0.001), and at 1 month (RR = 0.82, 95% CI 0.50 to 1.34, p = 0.43). At 2 years of
      follow-up, the incidence of nonfatal myocardial infarction was 7.6% in the
      invasive group, versus 9.1% in the conservative group (RR = 0.83, 95% CI 0.72 to
      0.96, p = 0.012), and at 1 month (RR = 0.93, 95% CI 0.73 to 1.19, p = 0.57). At a
      mean of 13 months of follow-up, there was a reduction in rehospitalization for
      unstable angina (RR = 0.69, 95% CI 0.65 to 0.74, p < 0.0001). CONCLUSIONS:
      Managing non-ST-segment elevation acute coronary syndromes by early invasive
      therapy improves long-term survival and reduces late myocardial infarction and
      rehospitalization for unstable angina.

PMID- 17010790
TI  - Percutaneous coronary intervention after fibrinolysis: a multiple meta-analyses
      approach according to the type of strategy.
AB  - OBJECTIVES: We performed a meta-analysis of randomized trials that enrolled ST
      segment elevation myocardial infarction patients treated with fibrinolysis to
      assess the potential benefits of: 1) rescue percutaneous coronary intervention
      (PCI) versus no PCI; 2) systematic and early (< or =24 h) PCI versus delayed or
      ischemia-guided PCI; 3) fibrinolysis-facilitated PCI versus primary PCI alone.
      BACKGROUND: The impact of PCI strategies after fibrinolysis on mortality or
      reinfarction remains to be established. METHODS: The meta-analysis was performed
      using the odds ratio (OR) as the parameter of efficacy with a random effect
      model. Fifteen randomized trials (5,253 patients) were selected. The primary end
      point was mortality or the combined end point of death or reinfarction. RESULTS:
      Rescue PCI for failed fibrinolysis reduced mortality (6.9% vs. 10.7%) (OR, 0.63;
      95% confidence interval [CI], 0.39 to 0.99; p = 0.055) and the rate of death or
      reinfarction (10.8% vs. 16.8%) (OR, 0.60; 95% CI, 0.41 to 0.89; p = 0.012)
      compared with a conservative approach. Systematic and early PCI performed during
      the "stent era" led to a nonsignificant reduction in mortality compared with
      delayed or ischemia-guided PCI (3.8% vs. 6.7%) (OR, 0.56; 95% CI, 0.29 to 1.05; p
      = 0.07) and to a 2-fold reduction in the rate of death or reinfarction (7.5% vs.
      13.2%) (OR, 0.53; 95% CI, 0.33 to 0.83; p = 0.0067). This benefit contrasted with
      a nonsignificant increase in the rate of both mortality (5.5% vs. 3.9%, p = 0.33)
      or death or reinfarction (9.6% vs. 5.7%, p = 0.06) observed in the "balloon era."
      Fibrinolysis-facilitated PCI was associated with more reinfarction as compared
      with primary PCI alone (5.0% vs. 3.0%) (OR, 1.68; 95% CI, 1.12 to 2.51; p =
      0.013) without significant impact on mortality (OR, 1.30; 95% CI, 0.92 to 1.83; p
      = 0.13). CONCLUSIONS: Our findings support rescue PCI and systematic and early
      PCI after fibrinolysis. However, the current data do not support fibrinolysis
      facilitated PCI in lieu of primary PCI alone.

PMID- 17010791
TI  - After fibrinolysis: is cardiac catheterization the answer?

PMID- 17010792
TI  - Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and
      clinical outcomes in patients with non-ST-segment elevation acute coronary
      syndrome undergoing coronary stenting.
AB  - OBJECTIVES: We analyzed the benefit of a 600-mg clopidogrel loading dose on
      platelet reactivity and clinical outcomes after stenting for non-ST-segment
      elevation acute coronary syndrome (NSTE ACS). BACKGROUND: High post-treatment
      platelet reactivity (HPPR = adenosine diphosphate 10 mumol x l(-1) [ADP]-induced
      platelet aggregation >70%) is a marker for low responders to dual antiplatelet
      therapy with increased risk of recurrent cardiovascular (CV) events after
      stenting for NSTE ACS. METHODS: A total of 292 consecutive NSTE ACS patients
      undergoing coronary stenting were included and randomly received a 300-mg (n =
      146) or 600-mg (n = 146) loading dose of clopidogrel at least 12 h before
      percutaneous coronary intervention. A single post-treatment blood sample was
      obtained before percutaneous coronary intervention to analyze maximal intensity
      of ADP-induced platelet aggregation and platelet surface expression of P
      selectin. One-month follow-up CV events were recorded. RESULTS: The ADP-induced
      platelet aggregation and expression of P-selectin were significantly lower in
      patients receiving 600 mg than in those receiving 300 mg (mean +/- SD: 50 +/- 19%
      vs. 61+/- 16%, p < 0.0001 and 0.38 +/- 0.24 arbitrary units vs. 0.60 +/- 0.40
      arbitrary units; p < 0.0001 respectively). Persistence of HPPR was less common in
      patients receiving 600 mg than in those receiving 300 mg (15 vs. 25%, p = 0.03).
      During the 1-month follow-up, 18 CV events (12%) occurred in the 300-mg group
      versus 7 (5%) in the 600-mg group (p = 0.02); this difference was not affected by
      adjustment for conventional CV risk factors (p = 0.035). CONCLUSIONS: In NSTE ACS
      patients undergoing coronary stenting, a 600-mg loading dose of clopidogrel shows
      its benefit on platelet reactivity and clinical prognosis.

PMID- 17010793
TI  - A subgroup analysis of the impact of prerandomization antithrombin therapy on
      outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST
      segment elevation acute coronary syndromes.
AB  - OBJECTIVES: The purpose of this study was to compare the effect of receiving
      pretreatment with antithrombin before randomization as well as overall efficacy
      and safety of enoxaparin versus unfractionated heparin (UFH) in the SYNERGY
      (Superior Yield of the New Strategy of Enoxaparin, Revascularization, and
      Glycoprotein IIb/IIIa Inhibitors) trial. BACKGROUND: The SYNERGY trial results
      demonstrated noninferiority in outcomes with enoxaparin compared with UFH.
      Randomized treatment was independent of prerandomization treatment. METHODS:
      Analyses were first performed on the 4 prerandomization subgroups: patients who
      received no antithrombin therapy and those who were treated with enoxaparin or
      UFH or both. Then, we focused on the subgroup of patients who received no
      pretreatment or were pretreated with and randomized to the same drug. Of the
      9,978 patients, 2,440 did not receive prerandomization therapy and 6,138 received
      consistent therapy through randomization. The primary end point was the composite
      of death and nonfatal myocardial infarction (MI) at 30 days. RESULTS: After
      adjustment for differences among the subgroups, no significant difference in the
      association between the 4 pretreatment groups and death or MI remained (p =
      0.171). The randomized treatment effect on 30-day death or MI tended to vary with
      pretreatment (p = 0.055 for interaction test after adjustment). Patients who
      received consistent therapy with enoxaparin had significantly less death or MI
      than patients randomized to UFH (adjusted p = 0.041) with a trend toward
      increased bleeding. CONCLUSIONS: Treatment with antithrombin therapy before
      randomization had potential impact on comparison of study drug effects. After
      adjustment for differences in baseline characteristics between subgroups,
      consistent therapy with enoxaparin might be superior to UFH in reducing death or
      nonfatal MI, with a modest excess in bleeding.

PMID- 17010794
TI  - Thrombus aspiration reduces microvascular obstruction after primary coronary
      intervention: a myocardial contrast echocardiography substudy of the REMEDIA
      Trial.
AB  - OBJECTIVES: The aim of this study was to clarify the role of microembolization in
      the genesis of microvascular obstruction (MO) after percutaneous coronary
      intervention (PCI). BACKGROUND: Fifty consecutive patients entered the myocardial
      contrast echocardiography (MCE) substudy of the REMEDIA (Randomized Evaluation of
      the Effect of Mechanical Reduction of Distal Embolization by Thrombus Aspiration
      in Primary and Rescue Angioplasty) trial, which defined the role of a new
      thrombus-aspirating device in preventing distal microembolization after PCI.
      METHODS: A total of 25 patients were randomized to be pretreated with thrombus
      aspiration before PCI of the culprit lesion and 25 received standard PCI. At 24
      h, 1 week, and 6 months after PCI, MCE was performed by Sonovue, and real-time
      imaging was performed by contrast pulse sequencing technology. Regional wall
      motion score index (WMSI), contrast score index (CSI), endocardial length of wall
      motion abnormality (WML) and contrast defect (CDL), end-diastolic and end
      systolic left ventricular (LV) volumes, and ejection fraction were calculated.
      RESULTS: At each time point, in patients treated with a thrombus-aspiration
      filter device, WMSI, CSI, WML, and CDL were significantly lower and ejection
      fraction higher (p < 0.05 vs. control patients), whereas LV volumes were slightly
      but not significantly smaller compared with control patients. In the overall
      study population, the extent of MO significantly correlated with temporal changes
      in LV volumes. CONCLUSIONS: Thrombus aspiration used at the time of PCI
      significantly reduces the extent of MO and myocardial dysfunction, although it
      does not have a significant favorable effect in preventing LV remodeling. Thus,
      the beneficial effect of thrombus aspiration occurs at the microvascular level,
      but additional mechanisms may play a role in influencing the final extent of MO,
      which strictly correlates with post-infarct LV remodeling.

PMID- 17010795
TI  - Variability in fluoroscopic X-ray exposure in contemporary cardiac
      catheterization laboratories.
AB  - OBJECTIVES: This study sought to assess fluoroscopic exposure rates in
      contemporary cardiac catheterization laboratories (CCL). BACKGROUND: Increasing
      attention is being focused on X-ray exposure during diagnostic and therapeutic
      cardiovascular procedures. METHODS: We measured fluoroscopic exposure rates
      (R/min) in 41 systems using a standardized methodology (National Electrical
      Manufacturers Association XR21 phantom). Measurements were obtained at 2
      different phantom thicknesses to simulate varying patient body habitus. RESULTS:
      Fluoroscopic exposure rates under medium (median 3.0 R/min, interquartile range
      1.4 R/min) and large (median 12.5 R/min, interquartile range 4.8 R/min) habitus
      conditions showed substantial variation. Fluoroscopic exposure was associated
      with simulated patient habitus, X-ray system type, vendor, and geographic region.
      Under medium habitus conditions, only 25% of systems operated within a zone of
      lower than average exposure rates and satisfactory image quality; this frequency
      diminished to 7% under large habitus conditions (p < 0.001). CONCLUSIONS: There
      is substantial variation (4- to 6-fold) in fluoroscopic exposure rates. This
      variation was not consistently associated with improved image quality. In the
      absence of a predictable benefit of higher (or lower) than average exposure
      rates, CCL quality improvement programs must minimize such potentially harmful
      variability in X-ray exposure.

PMID- 17010796
TI  - A repositionable valved stent for endovascular treatment of deteriorated
      bioprostheses.
AB  - OBJECTIVES: We report our animal experience of endovascular valve replacement
      (VR) of failed bioprosthesis (BP) using an original delivery catheter allowing
      repositioning of the valved stent (VS). BACKGROUND: Among the different devices
      designed for percutaneous VR, none has the potential for repositioning of a fully
      deployed VS. METHODS: Five sheep underwent, on beating heart, tricuspid VR with a
      stented BP. Prolapse of 1 leaflet was induced by tearing. For the endovascular
      tricuspid VR, we used a VS constructed with a nitinol self-expandable stent and a
      porcine stentless aortic valve. We also used an original delivery catheter,
      allowing repositioning of the VS through a compression or relaxation mechanism of
      the stent. RESULTS: Epicardial echocardiography and right ventriculography showed
      severe tricuspid regurgitation, with a regurgitant jet extending to the inferior
      vena cava. After surgical exposure to the infrarenal inferior vena cava, the VS
      was successfully implanted inside the failed BP in all cases. Repositioning of
      the fully deployed VS was always possible. Echocardiographic and macroscopic
      studies revealed adequate VS positioning, excellent leaflet opening, and absence
      of any intraprosthetic or periprosthetic leak. CONCLUSIONS: Endovascular VR was
      easily performed in sheep with failed BP in the tricuspid position. The novel
      delivery catheter allowed adequate repositioning of our fully deployed VS before
      its definitive release. One may anticipate that the safety improvement conferred
      by this new technology will certainly favor the development of percutaneous VR in
      clinical practice.

PMID- 17010797
TI  - Serum concentrations of adiponectin and risk of type 2 diabetes mellitus and
      coronary heart disease in apparently healthy middle-aged men: results from the 18
      year follow-up of a large cohort from southern Germany.
AB  - OBJECTIVES: We sought to assess the association between serum concentrations of
      adiponectin and long-term risk of type 2 diabetes mellitus (T2DM) and coronary
      heart disease (CHD) in initially healthy middle-aged men within the same
      representative population in Augsburg, southern Germany. BACKGROUND: It has been
      postulated that high serum concentrations of adiponectin, an emerging biomarker
      that is linked to insulin resistance and endothelial dysfunction, may be
      protective against T2DM and CHD. METHODS: Serum concentrations of adiponectin
      were determined in apparently healthy middle-aged men, sampled from the general
      population in 1984/1985 and followed until 2002. During this period, 115 of 887
      men had a newly diagnosed T2DM, and 126 of 937 men suffered from a CHD event.
      RESULTS: In a Cox model, after multivariable adjustment for cardiovascular risk
      factors, the hazard ratio of incident T2DM, comparing extreme tertiles of the
      adiponectin distribution, was 0.55 (95% confidence interval [CI], 0.35 to 0.89),
      and for incident CHD it was 0.62 (95% CI, 0.39 to 0.98). Further adjustment for
      high-density lipoprotein cholesterol (HDL-C) attenuated the association, which
      became formally non-significant. In joint analysis, men with low adiponectin and
      low HDL-C values showed a 2.63 times (95% CI, 1.66 to 4.15) increased incidence
      of T2DM and a 1.91 times (95% CI, 1.20 to 3.04) increased incidence of CHD after
      multivariable adjustment in comparison with men with high HDL-C and high
      adiponectin. CONCLUSIONS: For patients with low HDL-C values, additional
      measurement of adiponectin may be helpful to identify individuals at very high
      risk for T2DM and CHD.

PMID- 17010798
TI  - Impact of blockade of histamine H2 receptors on chronic heart failure revealed by
      retrospective and prospective randomized studies.
AB  - OBJECTIVES: The goal of this work was to determine whether the blockade of
      histamine H2 receptors is beneficial for the pathophysiology of chronic heart
      failure (CHF). BACKGROUND: Because CHF is one of the major life-threatening
      diseases, we need to find a novel effective therapy. Intriguingly, our previous
      study, which predicts the involvement of histamine in CHF, suggests that we
      should test this hypothesis in patients with CHF. METHODS: We selected 159
      patients who received famotidine among symptomatic CHF patients for the
      retrospective study. We blindly selected age- and gender-matched CHF patients
      receiving drugs for gastritis other than histamine H2 receptor blockers as a
      control group. For the prospective study, 50 symptomatic CHF patients were
      randomly divided into 2 groups. One group received famotidine of 30 mg/day for 6
      months, and the other group received teprenone. RESULTS: In the retrospective
      study, famotidine of 20 to 40 mg decreased both left ventricular end-diastolic
      and end-systolic lengths (LVDd and LVDs, respectively) and the plasma B-type
      natriuretic peptide (BNP) levels (182 +/- 21 vs. 259 +/- 25 pg/ml, p < 0.05) with
      unaltered fractional shortening (FS). In a randomized, open-label study, compared
      with teprenone, famotidine of 30 mg prospectively decreased both New York Heart
      Association functional class (p < 0.05) and plasma BNP levels (183 +/- 26 pg/ml
      vs. 285 +/- 41 pg/ml, p < 0.05); this corresponded to decreasing both LVDd (57 +/
      2 mm vs. 64 +/- 2 mm, p < 0.05) and LVDs (47 +/- 2 mm vs. 55 +/- 2 mm, p < 0.05)
      with unaltered FS (15 +/- 1% vs. 17 +/- 1%). The frequency of readmission because
      of worsening of CHF was lower in the famotidine group (4% and 24%, p < 0.05). On
      the other hand, teprenone had no effects on CHF. CONCLUSIONS: Famotidine improved
      both cardiac symptoms and ventricular remodeling associated with CHF. Histamine
      H2 receptor blockers may have therapeutic benefits for CHF.

PMID- 17010799
TI  - Histamine, mast cells, and heart failure: is there a connection?

PMID- 17010800
TI  - Increased level of pericardial insulin-like growth factor-1 in patients with left
      ventricular dysfunction and advanced heart failure.
AB  - OBJECTIVES: To test the hypothesis that the cardiac insulin-like growth factor-1
      (IGF-1) system is up-regulated in the failing heart, we measured the pericardial
      (cardiac) and plasma (circulating) IGF-1 levels in coronary artery disease
      patients. BACKGROUND: Local IGF-1 systems are regulated differently from the
      systemic IGF-1 system. The cardiac IGF-1 system is up-regulated by the increased
      left ventricular (LV) wall stress. However, it remains unknown how this system is
      affected in LV dysfunction and heart failure. METHODS: We measured the plasma and
      pericardial fluid levels of IGF-1 and brain natriuretic peptide (BNP) in 87
      coronary artery disease patients undergoing cardiac surgery, and examined their
      relationships with LV function and heart failure severity. The expressions of IGF
      1 and IGF-1 receptor proteins were examined in endomyocardial biopsies obtained
      from other patients with normal or impaired LV function. RESULTS: The pericardial
      IGF-1 and BNP levels were positively correlated with the plasma BNP level (both p
      < 0.001). The pericardial IGF-1 level was increased in heart failure patients,
      whereas the plasma IGF-1 level was rather decreased. The pericardial IGF-1 level
      was inversely correlated with the LV ejection fraction (p < 0.001), whereas the
      plasma IGF-1 level was not. Positive immunostaining for IGF-1 and IGF-1 receptor
      proteins was enhanced in myocardial biopsies from failing hearts compared with
      those from nonfailing hearts. CONCLUSIONS: The pericardial IGF-1 level was
      increased in patients with LV dysfunction and heart failure, whereas the plasma
      IGF-1 level was decreased. These results may indicate that up-regulation of the
      cardiac IGF-1 system serves as a compensatory mechanism for LV dysfunction.

PMID- 17010801
TI  - Phospholamban R14 deletion results in late-onset, mild, hereditary dilated
      cardiomyopathy.
AB  - OBJECTIVES: The purpose of this research was to determine the phenotypic spectrum
      associated with phospholamban gene (PLN) mutations. BACKGROUND: Inheritance
      contributes to the development of dilated cardiomyopathy. Mutations in the gene
      encoding PLN have been associated with dilated cardiomyopathy characterized by
      early onset and the presence of lethal ventricular arrhythmias. METHODS: We
      screened a cohort of 260 unrelated dilated cardiomyopathy patients from a
      tertiary care referral center for mutations in the PLN gene. RESULTS: Family
      history of cardiomyopathy was present in approximately one-half the individuals
      in this cohort. We identified 1 family with a deletion of arginine 14 in the PLN.
      Interestingly, unlike other individuals reported with the identical PLN mutation,
      these individuals were not diagnosed with dilated cardiomyopathy until their
      seventh decade when they were only mildly symptomatic with congestive heart
      failure. CONCLUSIONS: The identical PLN mutation can be associated with both mild
      and severe forms of dilated cardiomyopathy. Additionally, PLN mutations should be
      considered in late onset cardiomyopathy. (Genetics of Cardiovascular and
      Neuromuscular Disease; http://www.clinicaltrials.gov/ct/show/NCT00138931?order=1;
      NCT00138931)

PMID- 17010802
TI  - "Indeterminate" microvolt T-wave alternans tests predict high risk of death or
      sustained ventricular arrhythmias in patients with left ventricular dysfunction.
AB  - OBJECTIVES: This study tested the hypothesis that an "indeterminate" microvolt T
      wave alternans (MTWA) test, when due to ectopy, unsustained MTWA, or low exercise
      heart rate (HR), has prognostic significance similar to a positive MTWA test.
      BACKGROUND: MTWA testing, used to stratify risk of sudden or total mortality in
      patients with structural heart disease, has been limited by a substantial number
      of "indeterminate" tests. Indeterminate tests are due to patient factors-
      excessive ventricular ectopy during exercise, unsustained MTWA, or failure to
      achieve a HR of 105 beats/min for 1 min--or technical factors such as a noisy
      recording or an exercise protocol that causes an excessively rapid rise in HR.
      METHODS: Patients in sinus rhythm with left ventricular ejection fraction < or
      =0.40 underwent MTWA exercise tests, analyzed with the spectral method and
      classified by a computerized interpretation algorithm. The primary end point was
      all-cause mortality or documented non-fatal sustained ventricular arrhythmia
      (SVA). "Indeterminate" tests were reviewed jointly by 2 readers blinded to
      subsequent events to determine the primary reason for indeterminacy. RESULTS:
      Participants (N = 549) were 56 +/- 13 years and 71% male; 49% had ischemic
      cardiomyopathy. There were 40 deaths and 11 non-fatal SVA. Most (94%)
      indeterminate results were due to patient factors. The 2-year rate for death or
      SVA was 17.8% in patients with an "indeterminate" MTWA test compared with 12.3%
      in those with a positive test. CONCLUSIONS: In patients with left ventricular
      dysfunction, an "indeterminate" MTWA test due to patient factors predicted death
      or SVA at least as well as a positive test.

PMID- 17010803
TI  - Atrial arrhythmias after surgical maze: findings during catheter ablation.
AB  - OBJECTIVES: We describe the clinical and electrophysiologic characteristics and
      management of post "cut and sew" Maze arrhythmias in symptomatic patients.
      BACKGROUND: The Cox Maze procedure was developed as a surgical treatment of
      atrial fibrillation. Until recently, invasive electrophysiologic studies in
      patients with symptomatic post-operative arrhythmias in this patient population
      have not been described. METHODS: The management and clinical course of
      consecutive patients with post-Maze arrhythmias refractory to antiarrhythmic
      drugs (AADs) between January 2000 and December 2003 are presented. RESULTS:
      Twenty-three patients (15 men) presented 14 +/- 14 months after Maze surgery for
      treatment of atrial fibrillation (AF). Eight patients underwent "cut and sew"
      Maze for lone AF with no other surgical indication. Fifteen patients underwent
      the "cut and sew" Maze procedure in addition to another surgical procedure:
      mitral valve surgery (11 patients) and coronary artery bypass graft surgery (4
      patients). Eight patients (35%) had recurrent AF secondary to recovered
      conduction around the lines encircling the pulmonary veins. Five patients were
      documented to have focal atrial tachycardia, which was mapped to the coronary
      sinus in 3 patients, to the posterolateral right atrium in 1 patient, and to the
      left atrial (LA) septum in 1 patient. Four patients had right atrium incisional
      atrial flutter (AFL), and 6 had LA incisional AFL, which was mapped around the
      mitral valve annulus in 4 patients and around the right pulmonary veins in 2
      patients. Twenty-two of the 23 patients were treated successfully with
      radiofrequency ablation. At 1-year follow-up, 19 patients were arrhythmia-free
      and taking no AADs. CONCLUSIONS: After surgical "cut and sew" Maze, approximately
      one-third of patients experiencing atrial arrhythmias have AF secondary to
      pulmonary vein-left atrium conduction recovery. Moreover, incisional AFL seems to
      be a common finding in this group of patients. Catheter-based mapping and
      ablation of these arrhythmias seems to be feasible and effective.

PMID- 17010804
TI  - Does pregnancy increase cardiac risk for LQT1 patients with the KCNQ1-A341V
      mutation?
AB  - OBJECTIVES: The purpose of this study was to assess the pregnancy-related
      cardiovascular risk in LQT1 patients. BACKGROUND: Only 1 study addressed this
      issue in genotyped patients and reported that the highest risk is for LQT2
      patients. METHODS: This case-control study, performed in a cohort of patients
      from 22 families affected by LQT1 and all sharing the common KCNQ1-A341V
      mutation, involved 36 mutation carriers and 24 of their unaffected sisters for a
      total of 182 pregnancies. RESULTS: There were 3 (2.6%) cardiac events (2 cardiac
      arrests) in the 115 LQT1 pregnancies. Because they occurred only among the 27
      mothers with previous symptoms, all off-therapy, the risk for symptomatic
      patients is 11%, but decreases to 0 in symptomatic patients treated with beta
      blockers. Carriers and control subjects did not differ for the incidence of
      miscarriage (10% vs. 15%). Cesarean sections (C-sections), elective or owing to
      fetal distress, were performed more often in carriers than in non-carriers (27%
      vs. 14%). Beta-blocker therapy did not influence the prevalence of fetal
      distress. Among the infants born to carriers, all those with fetal distress were
      carriers of the A341V mutation (10 of 10, 100%). Among the offspring of the
      carriers, 48 of 92 (52%) were mutation carriers, and of those, 15% died suddenly
      at age 14 +/- 6 years. CONCLUSIONS: Women affected by the common KCNQ1-A341V
      mutation are at low risk for cardiac events during pregnancy and without excess
      risk of miscarriage; their infants delivered by C-section because of fetal
      distress are extremely likely to also be mutation carriers. Beta-blockers remain
      recommended. These conclusions likely apply to most LQT1 patients.

PMID- 17010805
TI  - Penetrance of mutations in plakophilin-2 among families with arrhythmogenic right
      ventricular dysplasia/cardiomyopathy.
AB  - OBJECTIVES: The purpose of our study was to characterize the penetrance of PKP2
      mutations among family members of people with arrhythmogenic right ventricular
      dysplasia/cardiomyopathy (ARVD/C) and to examine clinical features and predictors
      of disease among PKP2 mutation carriers. BACKGROUND: Arrhythmogenic right
      ventricular dysplasia/cardiomyopathy is an inherited cardiomyopathy characterized
      by fatty-fibrous myocardial replacement of the right ventricle, ventricular
      arrhythmias, and right ventricular dysfunction. Mutations in PKP2, the gene
      encoding plakophilin-2, are found in 11% to 43% of ARVD/C probands. METHODS: The
      study population was composed of 64 individuals in 9 families with an ARVD/C
      proband previously shown to carry a pathogenic PKP2 mutation. The diagnosis of
      ARVD/C was established based on task force criteria (TFC) set by the European
      Society of Cardiology. RESULTS: In addition to the probands, PKP2 mutations were
      present in 52% of relatives screened. Forty-nine percent of PKP2 mutation
      carriers met TFC. Among mutation carriers who did not meet full TFC, 50% met at
      least some TFC criteria besides family history. Pedigrees showed wide intra
      familial variability, ranging from severe disease with early death to individuals
      who were completely asymptomatic late in life. Male PKP2 mutation carriers were
      more likely to have structural and conduction abnormalities as determined by
      imaging studies, signal-averaged electrocardiography, and 24-h ambulatory
      electrocardiography (p < 0.05). CONCLUSIONS: PKP2 mutations in a group of North
      American families with ARVD/C have both reduced penetrance and variable
      expressivity. Gender may have an influence on penetrance of PKP2 mutations, with
      male mutation carriers more likely to develop specific phenotypic manifestations
      of this disease.

PMID- 17010806
TI  - Lower limb and abdominal compression bandages prevent progressive orthostatic
      hypotension in elderly persons: a randomized single-blind controlled study.
AB  - OBJECTIVES: This study sought to assess the efficacy of compression bandage of
      legs and abdomen in preventing hypotension and symptoms. BACKGROUND: Progressive
      orthostatic hypotension can occur in elderly people during standing. METHODS:
      Twenty-one patients (70 +/- 11 years) affected by symptomatic progressive
      orthostatic hypotension underwent 2 tilt-test procedures, with and without
      elastic bandage of the legs (compression pressure 40 to 60 mm Hg) and of the
      abdomen (compression pressure 20 to 30 mm Hg) in a randomized crossover fashion.
      Leg bandage was administered for 10 min and was followed by an additional
      abdominal bandage for a further 10 min. Symptoms were evaluated by a 7-item
      Specific Symptom Score (SSS) questionnaire before and after 1 month of therapy
      with elastic compression stockings of the legs (prescribed in all patients
      irrespective of the results of the tilt study). RESULTS: In the control arm,
      systolic blood pressure decreased from 125 +/- 18 mm Hg immediately after tilting
      to 112 +/- 25 mm Hg after 10 min of sham leg bandage and to 106 +/- 25 mm Hg
      after 20 min despite the addition of sham abdominal bandage. The corresponding
      values with active therapy were 129 +/- 19 mm Hg, 127 +/- 17 mm Hg (p = 0.003 vs.
      control), and 127 +/- 21 mm Hg (p = 0.002 vs. control). In the active arm, 90% of
      patients remained asymptomatic, versus 53% in the control arm (p = 0.02). During
      the month before evaluation, the mean SSS score was 35.2 +/- 12.1 with dizziness,
      weakness, and palpitations accounting for 64% of the total score. The SSS score
      decreased to 22.5 +/- 11.3 after 1 month of therapy (p = 0.01). CONCLUSIONS:
      Lower limb compression bandage is effective in avoiding orthostatic systolic
      blood pressure decrease and in reducing symptoms in elderly patients affected by
      progressive orthostatic hypotension.

PMID- 17010808
TI  - Neuregulin-1/erbB-activation improves cardiac function and survival in models of
      ischemic, dilated, and viral cardiomyopathy.
AB  - OBJECTIVES: We evaluated the therapeutic potential of a recombinant 61-residue
      neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple
      animal models of heart disease. BACKGROUND: Activation of the erbB family of
      receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart
      failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only
      critical for myocardium formation in early heart development but prevents severe
      dysfunction of the adult heart and premature death. Disabled erbB-signaling is
      also implicated in the transition from compensatory hypertrophy to failure,
      whereas erbB receptor-activation promotes myocardial cell growth and survival and
      protects against anthracycline-induced cardiomyopathy. METHODS: rhNRG-1 was
      administered IV to animal models of ischemic, dilated, and viral cardiomyopathy,
      and cardiac function and survival were evaluated. RESULTS: Short-term intravenous
      administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or
      cardiac contractility. In contrast, rhNRG-1 improved cardiac performance,
      attenuated pathological changes, and prolonged survival in rodent models of
      ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the
      ischemic model being additive to those of angiotensin-converting enzyme inhibitor
      therapy. In addition, despite continued pacing, rhNRG-1 produced global
      improvements in cardiac function in a canine model of pacing-induced heart
      failure. CONCLUSIONS: These beneficial effects make rhNRG-1 promising as a broad
      spectrum therapeutic for the treatment of heart failure due to a variety of
      common cardiac diseases.

PMID- 17010807
TI  - Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in
      pulmonary arterial hypertension.
AB  - OBJECTIVES: This study evaluated the safety and efficacy of inhaled treprostinil
      as add-on therapy to oral bosentan in patients with pulmonary arterial
      hypertension (PAH). BACKGROUND: The addition of a long-acting prostacyclin
      analogue via the inhaled route might be a safe and effective strategy to optimize
      therapy in PAH patients on bosentan. METHODS: Twelve patients with symptomatic
      PAH despite bosentan received either 30 microg of inhaled treprostinil 4 times
      daily (n = 6) or 45 microg 4 times daily (n = 6), via an ultrasonic nebulizer.
      Six-min walk distance (6MWD), functional class, and hemodynamics were assessed at
      baseline and 12 weeks. RESULTS: One patient was excluded from analysis due to the
      subsequent finding of pulmonary capillary hemangiomatosis. In the remaining 11
      patients, inhaled treprostinil was safe and well tolerated. Inhaled treprostinil
      was associated with an increase in 6MWD at 12 weeks (baseline 339 +/- 86, 12
      week, 1 h post-inhalation 406 +/- 121 m, 67-m change, p = 0.01). An improvement
      in 6MWD of 49 m from baseline was noted during the trough period, just before
      inhalation of treprostinil (p = 0.009). The 6MWD improvement of at least 10% was
      noted in 1 of 6 patients receiving 30 microg versus 5 of 6 receiving 45 microg.
      Over 12 weeks, significant decreases were noted in mean pulmonary arterial
      pressure (-10%) and in pulmonary vascular resistance (-26%). Functional class
      improved from III to II in 9 of 11 patients. CONCLUSIONS: This trial suggests
      that inhaled treprostinil is safe, well tolerated, and associated with
      significant improvements in exercise capacity, functional class, and pulmonary
      hemodynamics in symptomatic patients with PAH on bosentan.

PMID- 17010809
TI  - Novel--and "neu"--therapeutic possibilities for heart failure.

PMID- 17010810
TI  - Activation of apoptotic caspase cascade during the transition to pressure
      overload-induced heart failure.
AB  - OBJECTIVES: A pressure overload model was developed to simulate aortic stenosis
      and assess caspase activity during the transition to heart failure. BACKGROUND:
      Cardiomyocyte apoptosis is implicated in the pathogenesis of heart failure, and
      caspase activation is central to this pathophysiological process. METHODS: A
      total of 10 sheep were banded with variable aortic constriction devices,
      progressively inflated to increase left ventricular (LV) afterload. Serial LV
      endomyocardial biopsy samples were obtained to measure caspase activity and
      presence of apoptosis. RESULTS: Over the first 3 to 4 weeks, hypertrophy
      developed in the sheep (LV mass index 90.8 +/- 4.9 g/m2 vs. 44.0 +/- 3.0 g/m2, p
      < 0.01), followed by gradual dilatation of the left ventricle (diastolic LV
      internal diameter 4.23 +/- 0.08 cm vs. 3.39 +/- 0.07 cm, p < 0.01). Ventricular
      function remained stable until 7 to 8 weeks after banding, when there was
      significant deterioration (fractional shortening 18.3 +/- 2.4% vs. 46.9 +/- 2.6%,
      p < 0.01), associated with clinical heart failure. Serial LV endomyocardial
      biopsy samples were obtained at each echocardiographically defined stage (LV
      hypertrophy, LV dilation, and LV failure). Activity of caspases-3, -8, and -9
      (measured by specific fluorogenic peptide substrates and immunohistochemistry)
      increased progressively, particularly with the onset of myocardial dysfunction
      (caspase-3 7.92 +/- 1.19 vs. 1.00 +/- 0.15, caspase-8 1.94 +/- 0.21 vs. 1.00 +/-
      0.04, caspase-9 5.87 +/- 0.97 vs. 1.00 +/- 0.18 relative fluorescent units, p <
      0.05). No evidence of deoxyribonucleic acid (DNA) fragmentation, however, was
      identified by immunohistochemical assays. CONCLUSIONS: Activation of
      cardiomyocyte caspase enzymes occurs during the transition to heart failure,
      without completion of apoptotic DNA fragmentation. Increased activity of caspase
      8 and -9 suggests both mitochondrial and death-receptor mediated pathways are
      involved in this pathological process. Further knowledge of these pathways may
      stimulate development of apoptosis-based strategies for slowing progression of
      heart failure in aortic stenosis patients.

PMID- 17010812
TI  - President's page: acute coronary care: the yardstick of value.

PMID- 17010811
TI  - Bone marrow transplantation shows superior atheroprotective effects of gene
      therapy with apolipoprotein A-I Milano compared with wild-type apolipoprotein A-I
      in hyperlipidemic mice.
AB  - OBJECTIVES: We tested the hypothesis that gene therapy using apolipoprotein A-I
      Milano (apoA-IMilano) is more effective than that using wild-type apolipoprotein
      A-I (apoA-I) in reducing atherosclerosis. BACKGROUND: Apolipoprotein A-I Milano
      is a naturally occurring mutant with established antiatherogenic activity;
      however, its relative antiatherogenic efficacy compared with that of wild-type
      apoA-I remains unclear. METHODS: We performed bone marrow transplantation in
      female double-knockout mice lacking both the apoE and apoA-I genes using male
      donor mice-derived bone marrow that had been transduced with a retroviral vector
      alone or retroviral vector expressing wild-type apoA-I or apoA-IMilano gene under
      the control of macrophage-specific scavenger receptor A promoter. Mice were fed a
      high-cholesterol diet and killed 24 weeks after transplantation, at which time
      the extent of aortic atherosclerosis was determined. RESULTS: Compared with
      vector control (n = 12), apoA-IMilano gene therapy (n = 15) reduced aortic
      atherosclerosis by 65% (p < 0.001) and plaque macrophage immunoreactivity by 58%
      (p < 0.0001), whereas wild-type apoA-I (n = 11) reduced atherosclerosis by 25% (p
      = 0.1) and plaque macrophage immunoreactivity by 23% (p < 0.05). The apoA-IMilano
      gene therapy was significantly more effective in reducing atherosclerosis (p <
      0.05) and macrophage immunoreactivity (p < 0.001) compared with wild-type apoA-I.
      The circulating levels of cholesterol, lipoprotein profile, and apoA-IMilano or
      wild-type apoA-I were comparable among the groups. Apolipoprotein A-I Milano was
      more effective than wild-type apoA-I in promoting macrophage cholesterol efflux.
      CONCLUSIONS: Macrophage-specific expression of the apoA-IMilano gene is more
      effective than wild-type apoA-I in reducing atherosclerosis and plaque
      inflammation despite comparable circulating levels of the transgene and lipid
      profile.

PMID- 17010814
TI  - Of statistical significance: "trends" toward significance and optimism bias.

PMID- 17010815
TI  - Risk stratification with electrocardiographic-gated dobutamine stress imaging.

PMID- 17010817
TI  - Prolonged QTc interval and sudden cardiac death in older adults.

PMID- 17010819
TI  - ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac
      computed tomography and cardiac magnetic resonance imaging: a report of the
      American College of Cardiology Foundation Quality Strategic Directions Committee
      Appropriateness Criteria Working Group, American College of Radiology, Society of
      Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic
      Resonance, American Society of Nuclear Cardiology, North American Society for
      Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and
      Society of Interventional Radiology.

PMID- 17010820
TI  - Influenza vaccination as secondary prevention for cardiovascular disease: a
      science advisory from the American Heart Association/American College of
      Cardiology.
AB  - Evidence from cohort studies and a randomized clinical trial indicates that
      annual vaccination against seasonal influenza prevents cardiovascular morbidity
      and all-cause mortality in patients with cardiovascular conditions. The American
      Heart Association and American College of Cardiology recommend influenza
      immunization with inactivated vaccine (administered intramuscularly) as part of
      comprehensive secondary prevention in persons with coronary and other
      atherosclerotic vascular disease (Class I, Level B). Immunization with live,
      attenuated vaccine (administered intranasally) is not currently recommended
      [corrected] for persons with cardiovascular conditions. It is important to note
      that influenza vaccination coverage levels overall and in this population remain
      well below national goals and are marked by disparities across different age and
      ethnic groups. One of the barriers to vaccination for patients with
      cardiovascular disease is that cardiology practices frequently do not stock and
      administer influenza vaccine. Healthcare providers who treat individuals with
      cardiovascular disease can help improve influenza vaccination coverage rates by
      providing and strongly recommending vaccination to their patients before and
      throughout the influenza season.

PMID- 17010821
TI  - American College of Cardiology/American Heart Association 2006 update of the
      clinical competence statement on invasive
      electrophysiologystudies,catheterablation,andcardioversion: a report of the
      American College of Cardiology/American Heart Association/American College of
      Physicians Task Force on Clinical Competence and Training developed in
      collaboration with the Heart Rhythm Society.

PMID- 17010822
TI  - Alcohol awareness.

PMID- 17010823
TI  - Physical activity in patients who are severely mentally ill: feasibility of
      assessment for clinical and research applications.
AB  - Few studies have examined physical activity in patients who are severely mentally
      ill. We assessed feasibility and validity of using standardized self-report and
      objective measures of physical activity in 20 community-dwelling veteran
      patients, most with psychotic disorders and substance abuse in remission. Test
      retest reliability of a past week physical activity survey and the Community
      Healthy Activities Model Program for Seniors interview were evaluated with
      repeated interviews. RT3 accelerometer data provided objective physical activity
      data. Test-retest reliability and validity correlations for the self-report
      instruments were similar in magnitude to those reported for nonclinical adult
      samples. Some activity measures were correlated with cognitive status and quality
      of life. Results indicate that self-reported physical activity can provide valid
      information for clinical and research applications in mental health settings.
      Correlations between physical activity measures and psychiatric symptoms
      suggested interesting patterns for future study.

PMID- 17010824
TI  - Sense of belonging as connectedness, American Indian worldview, and mental
      health.
AB  - The concept of sense of belonging as connectedness is an abstract dimension of
      relatedness. Gaining an understanding of this concept within a cultural worldview
      has the potential to positively impact the mental health of ethnic minority
      populations. Sense of belonging as connectedness portrays the dynamic nature of
      human existence. The role of sense of belonging to interpersonal relationships
      and the well-being of individuals, family, and community is emphasized through
      the worldview of the American Indian population. It is a dynamic phenomenon of
      social significance.

PMID- 17010825
TI  - Outcomes of antipsychotic drug use in community-dwelling elders with dementia.
AB  - This study used administrative data from a large health care insurer in the
      southeast United States to describe the utilization pattern and health care
      outcomes of antipsychotic drug use in community-dwelling elders with dementia.
      Claims data from 959 unique cases were analyzed to address research aims.
      Overall, 27% of the sample was dispensed antipsychotic drugs, with the most
      prevalent type being atypical antipsychotic drugs. Individuals on any type of
      antipsychotic drug experienced more delirium, depression, hip fracture, falls,
      and syncope than those not on these drugs, even after controlling for age, sex,
      comorbidity, and number of other drugs prescribed. Implications for practice are
      discussed.

PMID- 17010827
TI  - "She took the time to make sure she understood": mental health patients'
      experiences of being understood.
AB  - The foundation of psychiatric/mental health nursing is the relationship between
      nurse and patient. Caring for persons with mental illness within the context of
      this relationship requires knowledge of the individual. To gain this knowledge,
      understanding the patient's perceptions and concerns is essential. Research
      suggests that this understanding does not always occur. The study reported here
      examined what it means to individuals with mental illness to be understood. In
      depth phenomenological interviews revealed three predominant themes: "I was
      important," "it really made us connect," and "they got on my level." Nurses can
      use these findings to improve the care of those with mental illness.

PMID- 17010826
TI  - Psychosocial characteristics and cardiovascular risk in African Americans with
      diabetes.
AB  - This descriptive study examined the ability of anxiety, depressive symptoms, and
      perceived social support to predict cardiovascular disease (CVD) risk in African
      American adults (N = 57) with type 2 diabetes but no prior history of CVD events.
      All completed a questionnaire packet during structured interviews. Participants
      had CVD risk profiles that indicated a greater than 20% probability of
      experiencing a CVD event in the next 2 to 10 years based on diabetes status
      alone. The variance (10%) in CVD risk accounted for by the variables examined was
      not statistically significant, suggesting that other variables may be better
      predictors of CVD risk.

PMID- 17010828
TI  - Inpatient psychiatric treatment: should we revive a shrinking system?

PMID- 17010829
TI  - Consider this... the DNP (Doctor of Nursing Practice).

PMID- 17010830
TI  - Intraoperative floppy-iris syndrome.

PMID- 17010832
TI  - Analytic formulas for error factors in IOL power calculation.

PMID- 17010834
TI  - Capsule stabilization devices.

PMID- 17010836
TI  - Another reason to celebrate.

PMID- 17010837
TI  - Posterior corneal surface changes after H-LASIK.

PMID- 17010838
TI  - Controls required to assess IOL movement during accommodation.

PMID- 17010839
TI  - History of the quick-chop technique.

PMID- 17010840
TI  - Consultation section: cataract surgical problem.

PMID- 17010853
TI  - Preoperative use of atropine to prevent intraoperative floppy-iris syndrome in
      patients taking tamsulosin.
AB  - Intraoperative floppy-iris syndrome (IFIS) is a recently identified condition
      associated with phacoemulsification in patients using the alpha1-antagonist
      tamsulosin (Flomax). Patients with IFIS manifest a triad of symptoms during
      cataract surgery: fluttering and billowing of iris stroma due to normal fluid
      movement, propensity of iris prolapse to phaco and side-port incisions, and
      progressive constriction of the pupil. Prevention of IFIS by withdrawing
      tamsulosin preoperatively has not shown consistent benefit. We describe the
      preoperative administration of atropine, which effectively prevented the
      occurrence of IFIS in patients receiving tamsulosin.

PMID- 17010854
TI  - Using endoscopy to teach cataract surgery.
AB  - Current methods of teaching cataract surgery include lectures, wet-lab sessions,
      and participation in real surgery. We describe a new method using a
      microendoscopic cyclophotocoagulation device during phacoemulsification cataract
      extraction and posterior chamber intraocular lens (IOL) implantation in 4 eyes of
      4 patients. Endoscopic visualization during surgery aided in construction of the
      corneal incision, location of the capsulorhexis edge, and estimation of the lens
      groove depth. It also demonstrated clinical findings not observable with the
      surgical microscope such as misplaced IOL haptics and residual lens cortex. Use
      of the endoscope enhanced the educational value of the surgery and the final
      surgical outcome.

PMID- 17010855
TI  - Cataract surgery management in patients taking tamsulosin staged approach.
AB  - PURPOSE: To demonstrate a progressive approach to the problems of intraoperative
      floppy-iris syndrome (IFIS) in cataract surgery caused by tamsulosin. SETTING:
      Cataract Treatment Center, Sunderland Eye Infirmary, Sunderland, United Kingdom.
      METHODS: Thirty-two eyes of 20 patients who were using tamsulosin had cataract
      surgery by the same surgeon using the same technique. Patients received standard
      preoperative eyedrops consisting of topical cyclopentolate, phenylephrine, and
      diclofenac. When necessary, intracameral phenylephrine, iris hooks, or both were
      used. All cases were videotaped and analyzed for surgical complications. RESULTS:
      The degree of IFIS manifested varied widely in the patients: Seventeen of 32 eyes
      (53%) had good mydriasis preoperatively (type 1 and type 2 pupils); however, in 7
      of the 17 eyes (43%), the pupils constricted later during surgery (type 2
      pupils). Twelve eyes (38%) had a mid-dilated pupil that sometimes constricted
      later (type 3 pupils), and 3 eyes (9%) had poor dilation at the beginning of
      surgery (type 4 pupils). There were no surgical complications attributed to IFIS.
      Full IFIS manifestation varied between eyes of the same patient. Some eyes
      required no intervention. Intraoperative pupil constriction was reversed with
      intracameral phenylephrine, which also prevented iris prolapse and billowing and
      further pupil constriction in patients who had medium to small pupils
      preoperatively. CONCLUSION: A staged approach in managing pupils in IFIS and
      using phenylephrine intracamerally when necessary effectively prevented serious
      intraoperative complications.

PMID- 17010856
TI  - Effect of a closed foldable equator ring on capsular bag shrinkage in cataract
      surgery.
AB  - PURPOSE: To evaluate the effect of a closed foldable equator ring (CFER) versus a
      conventional capsular tension ring (CTR) on capsular bag shrinkage. SETTING:
      Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany.
      METHODS: In this prospective study, 70 eyes of 70 patients were randomized to 2
      groups using a 1:1 block scheme. After uneventful cataract surgery, a capsular
      measuring ring was implanted in all eyes to measure the capsular bag diameter in
      vivo. In Group 1, a CTR was implanted in the capsular bag. In Group 2, a CFER was
      inserted. Biometric characteristics such as axial length and the horizontal and
      vertical corneal radii were measured preoperatively. The capsular bag diameter
      and capsulorhexis diameter were measured intraoperatively and 2 or 3 days as well
      as 1 and 3 months postoperatively. RESULTS: There were no statistically
      significant or clinically relevant between-group differences in covariants such
      as axial length, vertical and horizontal corneal radii, and capsulorhexis
      diameter. Eyes with the CTR had slight but statistically significant capsular bag
      shrinkage from a median of 10.4 to a median of 10.2 mm after 3 months (P<.001).
      Eyes with the CFER also had slight but statistically significant capsular bag
      shrinkage from a median of 10.3 to a median of 10.2 mm 3 months postoperatively
      (P = .021). At baseline, the CTR group had a larger capsular bag diameter, but
      there were no statistically significant differences between the groups at the 3
      month follow-up (P = .669). CONCLUSIONS: No clinically relevant capsular bag
      shrinkage was observed after implantation of a CFER or a CTR. The expected
      capsular bag shrinkage was the same in both groups.

PMID- 17010857
TI  - Effect of lens epithelial cell aspiration on postoperative capsulorhexis
      contraction with the use of the AcrySof intraocular lens: randomized clinical
      trial.
AB  - PURPOSE: To determine whether aspiration of lens epithelial cells (LECs) from
      under the anterior capsule reduces postoperative contraction of the capsulorhexis
      aperture. SETTING: Stoke Mandeville Hospital, Aylesbury, Buckinghamshire, United
      Kingdom. METHODS: This prospective randomized observer-masked study comprised 100
      patients who had routine phacoemulsification by the same surgeon at a district
      general hospital in the United Kingdom. The postoperative changes in
      capsulorhexis apertures and anterior capsule opacification (ACO) between Group A
      (aspiration of LECs) and Group B (control) were compared. Digital
      retroillumination images of the capsulorhexis aperture were taken 1 week and 3
      months postoperatively. The area of capsulorhexis aperture was determined with
      computer software, and capsule opacification was graded subjectively. RESULTS:
      Three months postoperatively, the mean decrease in capsulorhexis aperture was
      1.9% in Group A and 5.6% in Group B (P = .02). The ACO at 3 months was grade 2 in
      44% of eyes in Group A and in 61% in Group B (P = .13). CONCLUSION: Aspiration of
      LECs from the anterior capsule was a safe procedure that reduced capsulorhexis
      aperture contraction 3 months after cataract surgery.

PMID- 17010858
TI  - Posterior capsule opacification after implantation of a hydrophilic or a
      hydrophobic acrylic intraocular lens: one-year follow-up.
AB  - PURPOSE: To evaluate the effect of hydrophilic and hydrophobic single-piece
      acrylic intraocular lenses (IOLs) on posterior capsule opacification (PCO) after
      cataract surgery. SETTING: St. Erik's Eye Hospital, Stockholm, Sweden. METHODS:
      In a prospective study, 120 patients having cataract surgery were randomized to
      implantation of a hydrophilic acrylic IOL (BL27, Bausch & Lomb) or a hydrophobic
      acrylic IOL (AcrySof SA60AT, Alcon). Surgery was performed according to a
      standardized protocol by 1 of 3 surgeons. Best corrected visual acuity, contrast
      sensitivity, glare, intraocular pressure, and flare were measured 1 week, 3
      months, and 1 year after surgery. Posterior capsule opacification was assessed by
      digital retroillumination photography and analysis using POCOman software at 1
      year. The rate of neodymium:YAG (Nd:YAG) capsulotomy for each IOL was also
      recorded. RESULTS: At 1 year, the hydrophilic acrylic IOL group had a
      significantly greater percentage area and severity of PCO than the hydrophobic
      acrylic IOL group (P<.001). Two patients in the hydrophilic acrylic IOL group and
      4 in the hydrophobic acrylic IOL group had an Nd:YAG capsulotomy within the first
      year (P>.05). Contrast sensitivity was significantly better in the hydrophilic
      acrylic group at 3 months (P<.05); however, at 12 months no difference between
      the IOLs was observed. There was no significant difference in the other measured
      parameters. CONCLUSION: Patients with the hydrophilic acrylic BL27 IOL had a
      significantly greater percentage area and severity of PCO than those with the
      hydrophobic acrylic SA60AT IOL 1 year after surgery.

PMID- 17010859
TI  - One-year follow-up of bag-in-the-lens intraocular lens implantation in 60 eyes.
AB  - PURPOSE: To report the feasibility and clinical results of implanting a bag-in
      the-lens intraocular lens (IOL) designed to prevent posterior capsule
      opacification after cataract surgery. SETTING: Departments of Ophthalmology,
      University of Antwerp, Antwerp, Belgium, and University of Munich, Munich,
      Germany. METHODS: This prospective study comprised 63 eyes (55 patients; 7
      children, 48 adults) scheduled for cataract surgery and bag-in-the-lens IOL
      implantation. A posterior curvilinear capsulorhexis the same size as the anterior
      capsulorhexis was created for IOL insertion. After surgery, lens epithelial cell
      (LEC) proliferation was documented every 6 months with a minimum follow-up of 12
      months. RESULTS: Sixty of 63 eyes (95%) had implantation of the bag-in-the-lens
      IOL. Conversion to a conventional IOL was necessary in 2 cases. In 1 eye,
      postoperative luxation of the IOL into the vitreous occurred as a result of an
      oversized anterior and posterior capsulorhexis. Three eyes had early
      postoperative iris incarceration in the lens groove that required surgery. No LEC
      proliferation on the optic occurred during a mean follow-up of 22.7 months (range
      12 to 64 months); LEC proliferation was confined to the peripheral capsular bag.
      CONCLUSION: Lens epithelial cell proliferation was mild and confined to the
      periphery of the capsular bag during follow-up, and the bag-in-the-lens IOL optic
      remained clear.

PMID- 17010860
TI  - Fate of anterior capsule tears during cataract surgery.
AB  - PURPOSE: To determine the incidence of anterior capsule tears, at what stage of
      surgery they occurred, and their intraoperative behavior. SETTING: Ambulatory
      surgery center, Cincinnati Eye Institute, Cincinnati, Ohio, USA. METHODS: This 5
      year retrospective study was of patients having phacoemulsification with
      posterior chamber intraocular lens (IOL) implantation complicated by unplanned
      peripheral extension of the capsulorhexis tear or a radial anterior capsule tear.
      The operative notes and a videotape of the surgery were reviewed. The stage at
      which the tear was initially observed and when it extended were identified, as
      was whether the tear extended to the posterior capsule. Anterior vitrectomy and
      the design and location of the IOL implanted were also analyzed. RESULTS: A
      discontinuous anterior capsulorhexis or a break in the anterior capsule rim was
      observed in 21 eyes of 2646 cases, for an overall incidence of 0.79%. Anterior
      capsule tears were identified during ophthalmic viscosurgical device injection in
      1 eye, capsulorhexis in 13 eyes, hydrodissection in 2 eyes, phacoemulsification
      in 3 eyes, irrigation/aspiration (I/A) in 1 eye, and implantation of a prosthetic
      iris device in 1 eye. Seven of the 13 tears identified during the capsulorhexis
      were managed by redirecting the second edge of the "safety" capsulorhexis to
      incorporate the tear. In 14 eyes, the tear in the anterior capsule extended into
      the zonules; 4 of these tears were limited. Ten tears extended around the equator
      and through the posterior capsule, occurring during the hydrodissection in 1 eye,
      phacoemulsification in 2 eyes, I/A in 1 eye, and IOL implantation in 6 eyes. An
      anterior vitrectomy was required in 4 eyes that had posterior capsule
      involvement. Endocapsular fixation of a 1-piece acrylic IOL was achieved in 18
      eyes. Three eyes required implantation of a 3-piece acrylic IOL in the ciliary
      sulcus. CONCLUSIONS: Extension of an anterior capsule tear can complicate
      cataract surgery at any stage. Extension of the tear through the posterior
      capsule occurred in almost half the eyes with an anterior capsule tear, often
      requiring an anterior vitrectomy. Managing an anterior capsule tear can be
      challenging yet compatible with implantation of a posterior chamber IOL.

PMID- 17010861
TI  - Effect of total higher-order aberrations on accommodation in pseudophakic eyes.
AB  - PURPOSE: To analyze the effect of total higher-order aberrations (HOAs) on the
      range of accommodation in pseudophakic eyes and the size of near-vision
      optotypes. SETTING: Department of Ophthalmology, Nara Medical University, Nara,
      Japan. METHODS: The study comprised 30 patients (44 eyes) who were diagnosed with
      cataract at Nara University of Medical Science Hospital and Municipal Oyodo
      Hospital. Inclusion criteria included no other eye disorder and a best corrected
      distance acuity of 20/20 or better 1 month after cataract surgery. All patients
      had small-incision phacoemulsification followed by in-the-bag implantation of a
      monofocal intraocular lens (SA60AT, Alcon). All incisions were self-sealing.
      Accommodation in pseudophakic eyes was measured by the lens-loading method in an
      examination room under constant illumination. Ocular HOAs were measured using the
      KR-9000PW Hartmann-Shack wavefront analyzer (Topcon). RESULTS: The mean patient
      age was 75.8 years +/- 5.4 (SD) (range 64 to 83 years). The Pearson correlation
      coefficient (r) showed a significant positive correlation between the range of
      accommodation and Z7 (vertical coma) for a 4.0 mm pupil using the 1.0 near-vision
      optotype. There was a significant negative correlation between the range of
      accommodation and Z12 (spherical aberration) for a 4.0 mm pupil using the 1.0
      near-vision optotype (r = .311, P = .040 for Z7;r = -.365, P = .015 for Z12). No
      other parameter was significantly correlated with the range of accommodation.
      CONCLUSIONS: Measurement of accommodation in pseudophakic eyes by the lens
      loading method using the 1.0 near-vision optotype showed that eyes with larger
      vertical coma aberrations achieved a larger range of accommodation. In contrast,
      eyes with larger spherical aberrations had smaller amounts of accommodation. The
      size of the near-vision optotype may affect accommodation analysis in
      pseudophakic eyes.

PMID- 17010862
TI  - Depth of focus in eyes with diffractive bifocal and refractive multifocal
      intraocular lenses.
AB  - PURPOSE: To evaluate monocular and binocular depth of focus in eyes with
      different multifocal intraocular lens (IOLs) systems. SETTING: Department of
      Ophthalmology, Medical University of Vienna, Vienna, Austria. METHODS: In this
      comparative interventional study, binocular implantation of multifocal IOLs was
      performed in 3 groups. In the first group, 26 eyes of 13 patients received
      asymmetric Acri. Twin (Acri.Tec) IOLs, a near-weighted 733D in 1 eye and a
      distance-weighted 737D in the fellow eye. In the second group, 26 eyes of 13
      patients received a diffractive 811E IOL (Pharmacia). In the third group, 26 eyes
      of 13 patients received a refractive Array IOL (AMO). The visual acuity was
      tested monocularly and binocularly starting at 6 m in 0.50 diopter (D) defocusing
      steps. RESULTS: Distance visual acuity was best in eyes with the distance
      dominated 737D IOL; eyes with the other IOLs had comparable results. Binocular
      distance visual acuity was comparable between the Acri. Twin group and the 811E
      group. The Acri. Twin group had better distance visual acuity than the Array
      group (P< or =.048). Near visual acuity was best in eyes with the near-weighted
      733D, followed by the 737D and the 811E. Patients with Array IOLs had worse
      visual acuities at reading distance (between 33 cm and 40 cm) (P< or =.001).
      Patients with diffractive bifocal IOLs had better results than patients with
      refractive multifocal IOLs at reading distance (P< or =.018). CONCLUSION: The
      diffractive IOLs performed better than refractive IOLs. Asymmetric-weighted IOLs
      provided better binocular depth of field.

PMID- 17010863
TI  - Correction of hyperopia by intracorneal lenses: two-year follow-up.
AB  - PURPOSE: To assess the safety and efficacy of intracorneal lenses as a surgical
      alternative for the correction of hyperopia. SETTING: Al-Azhar University and El
      Magrabi Eye Hospital, Cairo, Egypt. METHODS: Twenty-three eyes of 21 patients who
      had a mean hyperopia of 4.3 diopters (D) +/- 0.71 (SD) (range +2.5 to +6.0 D)
      received Permavision lenses (Anamed Inc.), which are made of a highly permeable
      hydrogel with a water content of 78% and a refractive index close to that of
      corneal tissue (1.376). The Moria M2 microkeratome was used to make a 160 microm
      corneal flap with a diameter of +/-8.5 mm. The intracorneal lens was placed
      beneath the flap after minimal interface irrigation. RESULTS: Clinical
      examination showed mild corneal edema and a myopic shift during the first week
      postoperatively. In 17 eyes (73.9%), the postoperative uncorrected visual acuity
      was similar to the preoperative best corrected visual acuity (BCVA); 1 eye (4.3%)
      lost 1 line of preoperative BCVA. In 5 eyes (21.7%), various degrees of lens
      opacification with some degree of corneal haze were seen after uneventful follow
      up. Decentration of 0.5 to 1.0 mm was seen in 2 eyes (8.6%), 1 of which had the
      lens explanted because of significant opacification. Induced astigmatism was
      evident in 1 eye (-1.5 D). A total of 16 eyes (69.6%) were within +/-0.5 D of
      target, and 20 eyes (86.9%) were within +/-1.0 D (87%). No flap melting or
      extrusion of the lens was recorded in 24 months of follow-up. Night halos and
      glare were reported in 3 eyes; all had a lens diameter of 5.0 mm. CONCLUSIONS:
      Intracorneal hydrogel lenses were tolerated relatively well by stromal tissue,
      providing a reasonably stable and predictable way to correct moderate hyperopia.
      However, induced astigmatism, stromal opacification, decentration, and night
      halos and glare occurred in a significant number of eyes. To ensure safety, deep
      flap cuts are preferred and these eyes should be watched carefully to avoid
      decentration of the lens in the early postoperative period.

PMID- 17010864
TI  - Ultrasound energy and endothelial cell loss with stop-and-chop and nuclear
      preslice phacoemulsification.
AB  - PURPOSE: To evaluate ultrasound (US) energy and endothelial cell loss in cataract
      surgery using the stop-and-chop and nuclear preslice techniques. SETTING: Vision
      Institute, Federal University of Sao Paulo, Sao Paulo, Brazil. METHODS: This
      prospective clinical trial comprised 43 patients (50 eyes) with senile nuclear
      cataract who were randomly assigned to 1 of 2 groups: stop-and-chop (n=26) or
      nuclear preslice (n=24). The groups were divided according to nuclear density
      (NO(3) NC(3) and NO(4) NC(4)) using the Lens Opacity Classification System III. A
      full ophthalmic examination including biometry, specular microscopy, and
      pachymetry was performed preoperatively and postoperatively. The following
      parameters were evaluated: age, anterior chamber depth, lens thickness, axial
      length, phaco time and power, effective phaco time (EPT), infusion volume, ocular
      inflammation, endothelial cell loss, and best corrected visual acuity (BCVA).
      RESULTS: Phacoemulsification time, power, and EPT were significantly higher in
      the stop-and-chop group. Infusion volumes did not vary significantly between the
      groups. A significant decrease in endothelial cell density occurred
      postoperatively and was similar with both techniques (stop-and-chop, 8.70%;
      nuclear preslice, 8.72%). The BCVA improved significantly in both groups. No
      significant correlations were found between endothelial cell loss and either
      technique. CONCLUSIONS: Ultrasound energy consumption was lower with the nuclear
      preslice technique. Both techniques had similar results including endothelial
      cell loss.

PMID- 17010865
TI  - Local corneal thickness changes after small-incision cataract surgery.
AB  - PURPOSE: To assess whether a temporal limbal-corneal incision approach for
      phacoemulsification cataract surgery induces a gradient in corneal thickening
      along the horizontal meridian. SETTING: Department of Ophthalmology, Medical
      University of Vienna, Vienna, Austria. METHODS: Corneal thickness in 21 eyes of
      21 patients was measured preoperatively as well as 1 day, 1 week, and 1 and 3
      months after phacoemulsification through a temporal limbal-corneal incision.
      Measurements were performed using partial coherence interferometry (PCI) with a
      commercial instrument, the ACMaster (Carl Zeiss Meditec, Jena). Measurements were
      taken along the horizontal meridian centrally along the visual axis at 1.5 mm,
      3.0 mm, and 4.5 mm eccentricity. RESULTS: Preoperatively, there were slight nasal
      temporal differences in corneal thickness at all eccentricities. The mean
      thickness was 522 microm +/- 34 (SD) at 1.5 mm nasally and 513 +/- 36 microm at
      1.5 mm temporally (P<.01). On day 1, there was a significant mean increase in
      corneal thickness (38 +/- 43 microm) along all locations. The thickening was
      slightly more pronounced in the periphery than in the center, a difference not
      reaching statistical significance. At 1 week, corneal thickness returned almost
      to baseline at all locations except for 3.0 mm temporally, where it was slightly,
      but not significantly, thicker (mean 8 +/- 14 mum). At 1 month, corneal thickness
      at the 3.0 mm temporal location returned to baseline. CONCLUSIONS: A nasal
      temporal difference in corneal thickness was found preoperatively in all
      patients. Phacoemulsification through a temporal limbal-corneal incision caused
      an increase in corneal thickness along the horizontal meridian 1 day after
      surgery. The prolonged corneal thickening at 3.0 mm eccentricity temporally could
      be a result of the proximity to the incision site.

PMID- 17010866
TI  - Primary intraocular lens implantation in infants: complications and visual
      results.
AB  - PURPOSE: To evaluate the complications and visual results in a consecutive series
      of patients having cataract extraction with intraocular lens (IOL) implantation
      in the first year of life. SETTING: St. Erik's Eye Hospital, Stockholm, Sweden.
      METHODS: This retrospective study comprised 28 children (31 eyes) who had
      cataract surgery with primary IOL implantation. RESULTS: The median age at
      surgery was 2.5 months (range 8 days to 10 months). The median follow-up was 36
      months. Two newborns with persistent fetal vasculature (PFV) who had surgery at 8
      days and 17 days, respectively, developed intraoperative vitreous hemorrhage; a
      retinal detachment developed in 1 of the eyes. Intraocular lens luxation occurred
      in 2 infants with PFV. Seventy percent of eyes developed opacification of the
      visual axis that required additional surgery. Chronic glaucoma developed in 2
      eyes and transitory glaucoma in 1 eye. Two of the glaucoma cases occurred in eyes
      with PFV. In 7 eyes of 4 infants with bilateral cataract, the median visual
      acuity was 20/63 (range 20/25 to 20/100). In 12 infants with unilateral cataract
      without PFV, 7 achieved a visual acuity between 20/32 and 20/200 (median 20/63),
      4 achieved counting fingers (CF), and 1 achieved light perception. In 12 eyes
      with PFV, 2 achieved a visual acuity of 20/200 and the rest achieved CF or worse.
      CONCLUSIONS: After-cataract with membrane formation was the main complication in
      infants with primary IOL implantation. The glaucoma incidence was low at the last
      follow-up.

PMID- 17010867
TI  - Cataract extraction outcomes in patients with Fuchs' heterochromic cyclitis.
AB  - PURPOSE: To analyze the visual outcomes and complication rate after cataract
      extraction and posterior chamber intraocular lens (PC IOL) implantation in
      patients with Fuchs' heterochromic cyclitis. SETTING: L.V. Prasad Eye Institute,
      Hyderabad, India. METHODS: This retrospective nonrandomized interventional study
      comprised 103 patients who were examined at the uvea clinic at L.V. Prasad Eye
      Institute between March 2000 and March 2004 and who were diagnosed with Fuchs'
      heterochromic cyclitis and cataract. They had extracapsular cataract extraction
      or phacoemulsification with IOL implantation. Outcomes measures were
      postoperative visual acuity, ocular inflammation, and complication rate. RESULTS:
      There were 57 men and 54 women in the study; the mean age was 31.36 years +/-
      11.55 (SD) (range 10 to 60 years). Postoperative best corrected visual acuity
      (BCVA) at 5 weeks was 20/40 or greater in 91 patients (88.3%) (95% confidence
      interval [CI], 82.1-94.5). Eight patients (7.8%) had vitreous inflammation 5
      weeks postoperatively. Five patients (4.9%) preoperatively and 3 patients (2.9%)
      postoperatively had elevated intraocular pressure. Clinically detected cystoid
      macular edema developed in 1 patient. The mean follow-up was 12.9 months in 53
      patients. At the final follow-up, 49 of 53 patients (91.5%) (95% CI, 99.0-84.0)
      had a visual acuity of 20/40 or greater. Ten eyes (18.9%) had mild anterior
      chamber reaction. Decreased visual acuity (20/40 or worse) was the result of
      anterior chamber reaction in 4 patients, glaucoma in 3 patients, vitreous
      inflammation in 2 patients, and posterior capsule opacification, corneal edema,
      macular hole, and astigmatism in 1 patient each. CONCLUSIONS: Cataract surgery
      with PC IOL implantation in patients with Fuchs' heterochromic cyclitis resulted
      in good visual outcomes. Postoperative inflammation was mild and developed in few
      cases.

PMID- 17010868
TI  - Lightless cataract surgery using a near-infrared operating microscope.
AB  - PURPOSE: To describe the near-infrared (NIR) operating microscopy (NIOM) system
      using the NIR wavelength as the illumination source and to evaluate the
      feasibility of this system for lightless cataract surgery. SETTING: HenAm Kim Eye
      Center, Haenam-Gun, South Korea. METHODS: In this noncomparative interventional
      case series, cataract surgery was performed in 4 patients with bilateral cataract
      using the NIOM system in 1 eye and conventional microscopy in the fellow eye. The
      primary components of the system include an optical filter, a stereoscopic
      camera, head-mounted displays, and a recording system. This system uses invisible
      NIR (wavelength 850 to 1300 nm) illumination to facilitate cataract surgery
      without light. The differences between the NIOM system and conventional
      microscopy during cataract surgery were evaluated. RESULTS: The NIOM system
      provided excellent 3-dimensional viewing in real time. The image resolution was
      sufficient while performing all steps of cataract surgery. Immediately
      postoperatively and at 10 and 30 minutes and 1 hour, the visual acuity was better
      in the 4 eyes in which the NIOM system was used than in the 4 eyes in which
      conventional microscopy was used. However, using the NIOM system required good
      surgical skill. CONCLUSIONS: Lightless cataract surgery using the NIOM system
      seems useful for obtaining good visual acuity immediately postoperatively. The
      system may also reduce the incidence of light-induced retinal toxicity and the
      need for mydriatic administration and be a good educational tool.

PMID- 17010869
TI  - Bacterial contamination in the anterior chamber after povidone-iodine application
      and the effect of the lens implantation device.
AB  - PURPOSE: To assess the incidence of anterior chamber bacterial contamination
      during cataract surgery, and compare results of injector implantation and forceps
      implantation of foldable intraocular lenses (IOLs). SETTING: Department of
      Ophthalmology and Institute of Medical Microbiology, Semmelweis University,
      Budapest, Hungary. METHODS: This prospective randomized controlled clinical study
      comprised 97 eyes of 96 patients. Antibiotic eyedrops were not used; however,
      povidone-iodine 10% solution was used to prepare the eyebrow and eyelids and
      povidone-iodine 5% to disinfect the ocular surface. A Steri-Drape (3M) was used
      to surround the eye. Aqueous fluid samples were aspirated from the anterior
      chamber at the beginning and the end of surgery. The samples were cultured for 14
      days under aerobic and anaerobic conditions simultaneously. Cataract surgery was
      performed using a sutureless, superotemporal, clear corneal phacoemulsification
      technique. The IOL was implanted with an injector (n = 47) or a forceps (n = 50),
      with the instrument randomly selected. The frequency of positive bacterial
      cultures with each implantation method was compared using the Fisher exact test.
      RESULTS: Bacteria were found in the conjunctival samples in 21 eyes (21.65%)
      before povidone-iodine application and in 4 eyes (4.12%) after disinfection. The
      anterior chamber sample before surgery was culture positive for Staphylococcus
      epidermidis in 2 eyes and for Micrococcus luteus in 1 eye. After surgery, the
      culture was positive for S epidermidis in 1 eye (2.15%) in the injector group and
      1 eye (2.00%) in the forceps group (P = .74). Neither sample came from an eye
      that had a positive culture preoperatively. There were no intraoperative
      complications. CONCLUSIONS: In uneventful clear corneal phacoemulsification,
      meticulous technique can prevent antibiotic use during surgery. No difference in
      anterior chamber bacterial contamination was found between IOL implantation using
      an injector or a forceps.

PMID- 17010870
TI  - Outbreak of toxic anterior segment syndrome associated with glutaraldehyde after
      cataract surgery.
AB  - PURPOSE: To present clinical findings of a cluster of cases of toxic anterior
      segment syndrome (TASS) after uneventful phacoemulsification cataract surgery.
      SETTING: Department of Ophthalmology, Akdeniz University, Antalya, Turkey.
      METHODS: Six eyes of 6 patients developed TASS after uneventful
      phacoemulsification cataract surgery with implantation of a 3-piece acrylic IOL
      performed by 2 ophthalmologists on the same day. Clinical findings included
      corneal edema, Descemet's membrane folds, anterior chamber reaction, fibrin
      formation, and irregular, dilated, and unreactive pupils. RESULTS: Glutaraldehyde
      2% solution was used inadvertently by the operating room staff who cleaned and
      sterilized reusable ocular instruments before autoclaving. None of the affected
      corneas improved. Additional surgical procedures were required and included
      penetrating keratoplasty, trabeculectomy, and glaucoma tube implantation.
      CONCLUSIONS: Glutaraldehyde in concentrations generally used for cold
      sterilization is highly toxic to the corneal endothelium. The operating room
      staff involved in sterilizing instruments should be well educated about and
      careful to follow the protocols to properly clean and sterilize reusable ocular
      instruments.

PMID- 17010871
TI  - Surgical-glove-related diffuse lamellar keratitis after laser in situ
      keratomileusis: long-term outcomes.
AB  - PURPOSE: To study the long-term refractive results in eyes that developed
      surgical-glove-related diffuse lamellar keratitis (DLK) after laser in situ
      keratomileusis (LASIK). SETTING: Department of Ophthalmology, Hospital
      Provincial, Toledo, Spain. METHODS: This retrospective review analyzed an
      epidemic of surgical-glove-related DLK over a 5-month period at a single
      hospital. Twenty-four eyes (24 patients) that developed DLK (DLK group) were
      compared to 30 eyes (30 consecutive patients) that had surgery during the same
      time but had an uneventful postoperative course (control group). Follow-up was 12
      months in all cases. RESULTS: Twelve months after LASIK, the mean spherical
      equivalent was 0.14 diopter (D) +/- 0.36 (SD) in the DLK group and -0.07 +/- 0.33
      D in the control group (P=.03). The mean uncorrected visual acuity was 0.91 +/-
      0.18 and 0.90 +/- 0.17, respectively (P = .81). The mean best spectacle-corrected
      visual acuity (BSCVA) was 0.97 +/- 0.08 in the DLK group and 0.99 +/- 0.06 in the
      control group (P = .42). At 1 year, 91.7% of eyes in the DLK group and 93.3% of
      eyes in the control group were within +/-0.50 D of the attempted correction (P =
      .82). The BSCVA was 1.0 or better in 87.5% and 93.3%, respectively (P =.46).
      CONCLUSIONS: Early diagnosis and appropriate treatment of glove-related DLK
      provided visual outcomes that were similar to those in eyes with an uneventful
      postoperative course. These good results are consistent with those in studies of
      classic DLK.

PMID- 17010872
TI  - Intrastromal ring segment insertion using a femtosecond laser to correct pellucid
      marginal corneal degeneration.
AB  - PURPOSE: To assess the outcomes of intrastromal ring segment (Intacs, Addition
      Technology) implantation using a femtosecond laser in patients with pellucid
      marginal corneal degeneration. SETTING: Kudret Eye Hospital, Ankara, Turkey.
      METHODS: In this retrospective noncomparative case series, 9 eyes of 6 patients
      with pellucid marginal corneal degeneration had implantation of Intacs segments
      by a femtosecond laser technique. Preoperative and postoperative evaluations
      included slitlamp examination, uncorrected (UCVA) and best corrected (BCVA)
      visual acuities, and keratometry by a Pentacam Scheimpflug camera (Oculus
      Opticgerate GmbH). All parameters were reviewed within 6 months. RESULTS: Intacs
      were successfully implanted in all eyes. The UCVA significantly improved from
      preoperatively to 6 months after Intacs implantation (mean 0.18 +/- 0.24 [SD] and
      0.53 +/- 0.23, respectively). The mean difference between the preoperative and
      postoperative UCVA was 3.5 +/- 1.6 lines (P = .008). The BCVA also significantly
      improved from preoperatively to 6 months after implantation (mean 0.63 +/- 0.26
      and 0.85 +/- 0.18 at 6 months, respectively). The Snellen BCVA was 1.0 in 5 eyes
      postoperatively. The mean difference between preoperative and postoperative BCVA
      was 2.3 +/- 51 lines (P = .011). The mean preoperative spherical refraction
      decreased from -3.86 +/- 2.91 diopters (D) to -2.77 +/- 1.43D (P = .091) and the
      mean cylindrical refraction, from -2.41 +/- 2.27 D to -0.94 +/- 1.07 D (P =
      .046). The mean central corneal curvature decreased from 48.20 +/- 4.19 D
      preoperatively to 46.90 +/- 5.00 D (P = .008) at 6 months and the mean posterior
      elevation, from 53.88 +/- 21.72 microm to 32.55 +/- 11.23 microm (P = .008).
      CONCLUSION: Intacs insertion using a femtosecond laser was safe and efficient in
      the correction of pellucid marginal corneal degeneration.

PMID- 17010873
TI  - Hydrophilic acrylic intraocular lens as a drug-delivery system for fourth
      generation fluoroquinolones.
AB  - PURPOSE: To evaluate the ability and safety of a hydrophilic acrylic intraocular
      lens (IOL) as a drug-delivery system for commercially available gatifloxacin and
      moxifloxacin. SETTING: David J. Apple, MD, Laboratories for Ophthalmic Research,
      John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences,
      University of Utah, Salt Lake City, Utah, USA. METHODS: Thirty rabbits were
      divided into 2 similar groups. In Group A (15 rabbits, 30 eyes), hydrophilic
      acrylic IOLs (C-flex, Rayner Intraocular Lenses, Ltd.) presoaked for 24 hours in
      commercially available solutions of gatifloxacin 3 mg/mL or moxifloxacin 5 mg/mL
      were implanted after evacuation of the crystalline lens. Group B (15 rabbits, 30
      eyes) had topical preoperative and postoperative cataract prophylaxis with
      gatifloxacin 3 mg/mL or moxifloxacin 5 mg/mL; IOLs that were not presoaked were
      also implanted after evacuation of the crystalline lenses. In both groups,
      aqueous humor samples were taken 4, 8, or 12 hours after IOL implantation (5 eyes
      at each time point) to determine the antibiotic concentrations. Clinical
      examinations were performed 24 hours postoperatively. RESULTS: The antibiotic
      concentrations in Group A (presoaked IOLs) were statistically significantly
      higher than those in Group B (topical) for both antibiotics in all postoperative
      samples except moxifloxacin at 12 hours. In both groups, there was no
      statistically significant difference between the concentrations of the 2
      antibiotics. No eye showed signs of clinical toxicity. CONCLUSION: Results show
      the C-flex IOL is a safe and effective drug-delivery system for fourth-generation
      fluoroquinolones.

PMID- 17010874
TI  - Long-term capsular bag survival without functional lens epithelial cells.
AB  - PURPOSE: To evaluate the survival of the capsular bag without the support of
      functional lens epithelial cells (LECs). SETTING: David J. Apple, MD,
      Laboratories for Ophthalmic Devices Research, John A. Moran Eye Center,
      Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake
      City, Utah, USA. METHODS: One hundred slides of cadaver pseudophakic eyes (from
      1991 to 2000) stained with hematoxylin and eosin were analyzed to determine the
      presence of Soemmering's ring, integrity of the capsular bag, fixation
      configuration of the haptics, and presence and functionality of the LECs.
      RESULTS: A Soemmering's ring was present in 69% of cases. The capsular bags were
      intact in 100% of cases. In-the-bag fixation was seen in 44% of cases. In 89% of
      cases, either no cells or nonfunctional LECs were found. CONCLUSION: Results
      suggest the capsular bag can survive anatomically without the support of
      functioning LECs.

PMID- 17010875
TI  - Genipin suppression of fibrogenic behaviors of the alpha-TN4 lens epithelial cell
      line.
AB  - PURPOSE: To determine in a lens epithelial cell line, alpha-TN4, whether genipin,
      an intestinal metabolite component of the herbal medicine inchin-ko-to,
      suppresses profibrogenic myofibroblast generation and upregulation of fibrogenic
      cytokines and to evaluate the potential benefit of the medicine in preventing
      posterior capsule opacification (PCO). SETTING: Department of Ophthalmology,
      Wakayama Medical University, Wakayama, Japan. METHODS: In this study, alpha-TN4
      cell proliferation, migration, and expression of alpha-smooth muscle actin (alpha
      SMA), the hallmark of myofibroblast generation, were assayed with a colorimetric
      assay, scratch wound assay, immunohistochemistry, and Western blot analysis. Gene
      expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue
      growth factor (CTGF) was characterized with real-time reverse transcription
      polymerase chain reaction. In addition, p38 mitogen-activated protein kinase (p
      38 MAPK), extracellular signal-regulated kinase (ERK) limb, and Smad signalings
      were evaluated by Western blotting and immunohistochemistry. Cytotoxicity of
      genipin was evaluated using a commercial colorimetric assay kit for nuclear
      matrix protein 41/7 (NMP41/7) in culture medium. RESULTS: Genipin suppressed cell
      proliferation and migration in association with inhibition of Smad and p38 MAPK
      phosphorylation, although ERK signaling was enhanced. Genipin suppressed mRNA
      expression of TGF-beta1 and CTGF. Cytoplasmic fiber formation declined based on
      less intense alpha-SMA immunocytochemical staining. However, alpha-SMA protein
      expression was actually not altered. This negative result suggests that genipin
      attenuated formation of alpha-SMA-containing cytoskeleton. Treatment of the cells
      with genipin for 48 hours did not increase the release of NMP41/7 to the medium,
      indicating this compound is not cytotoxic. CONCLUSION: Because genipin suppressed
      alpha-TN4 lens cell fibrogenic behaviors, it may be of therapeutic value in
      preventing PCO.

PMID- 17010876
TI  - Cyclooxygenase 2 expression in rat corneas after ethanol exposure.
AB  - PURPOSE: To evaluate the effects of ethanol exposure of the cornea on
      inflammation in corneal epithelium. SETTING: Department of Ophthalmology,
      Wakayama Medical University, Wakayama, Japan. METHODS: One cornea of Wistar rats
      (n = 60) was exposed to ethanol 20% for 30 seconds. The animals were killed 0.5,
      1.0, 1.5, 2.0, 6.0, 12.0, 24.0, 48.0, or 72.0 hours or 7 days after treatment.
      The paraffin section or cryosection of the treated eyes was processed for
      histology; immunohistochemistry for cyclooxygenase 2 (COX2); p65 subunit of
      nuclear factor kappa B (NF-kappaB), which is the major transcription factor
      involved in COX2 expression; phospho-IkappaB; or in situ hybridization for COX2
      mRNA. RESULTS: In the uninjured corneas, faint immunoreactivity for COX2 was
      detected in the basal cells of the corneal epithelium, but not in other cell
      layers. Cyclooxygenase 2 mRNA was not observed in the injured epithelium; it was
      expressed 2 hours after ethanol exposure, but not 3 hours or later after
      treatment. The COX2 protein was detected in the corneal epithelium throughout the
      epithelial layers from 3 to 72 hours, but not at 7 days. The p65 of NF-kappaB
      translocated to the nuclei of corneal epithelium 3 to 24 hours after treatment
      but was not seen in the nuclei 48 hours after treatment. Phospho-I kappaB was
      detected in corneal epithelium 6 hours after treatment, but not 12 hours or
      later. CONCLUSION: Ethanol exposure activated NF-kappaB and upregulated COX2
      expression, which may cause inflammation in corneal tissue.

PMID- 17010877
TI  - Cellular effects of mitomycin-C on human corneas after photorefractive
      keratectomy.
AB  - PURPOSE: To investigate the effects of mitomycin-C (MMC) on epithelial and
      keratocyte cell kinetics after photorefractive keratectomy (PRK) using an in
      vitro human cornea model. SETTING: Department of Academic Ophthalmology, Rayne
      Institute, St. Thomas' Hospital, London, United Kingdom. METHODS: Twenty-four
      human eye-bank corneas were placed in a specially designed acrylic corneal holder
      and cultured using the air-interface organ culture technique for up to 4 weeks.
      The corneas were divided into 3 groups. Group 1 consisted of 8 human corneas that
      had -9.00 diopter (D) myopic PRK without MMC application. Group 2 consisted of 8
      corneas that had -9.00 D PRK with MMC (0.2 microg/mL) application for 1 minute on
      the stromal surface after ablation. Group 3 consisted of 8 corneas that had -9.00
      D PRK with 2-minute exposure to MMC (0.2 microg/mL). Temporal events in
      epithelial and keratocyte cell kinetics were evaluated using digital imaging,
      confocal microscopy, and light microscopy. RESULTS: Epithelial latency was
      significantly delayed with MMC application in Groups 2 and 3 (P<.001). Epithelial
      migration was delayed in Group 3 (2-minute exposure) compared to migration in
      Group 2 (P<.04), with a consequent delay in epithelial closure (P<.001). Group 3
      corneas had poorly differentiated epithelium that was significantly thinner than
      in Groups 1 and 2 (P<.0001). A significant delay in keratocyte regeneration
      occurred after MMC application (P<.0005). At 4 weeks, the anterior stromal cell
      density was significantly lower in Group 3 than Group 2 (P<.001). There were no
      significant differences in the mid- and posterior stromal keratocyte density
      between the groups. CONCLUSIONS: Results suggest that epithelial healing after
      MMC is characterized by prolonged latency and decreased migration rate dependent
      on exposure time. Mitomycin C application did not result in increased loss of
      keratocytes, but it significantly delayed keratocyte repopulation in the anterior
      stroma. The use of MMC 0.2 microg/mL for 1 minute resulted in optimum modulation
      of healing characterized by reduced keratocyte activation with normal epithelial
      differentiation.

PMID- 17010878
TI  - White paper: Utilization, appropriate care, and quality of life for patients with
      cataracts.

PMID- 17010879
TI  - Ultrasound biomicroscopy in traumatic aniridia 2 years after phacoemulsification.
AB  - A 45-year-old man with retinitis pigmentosa experienced total aniridia in the
      left eye due to direct blunt trauma 2 years after uneventful bilateral
      phacoemulsification via a 3.5 mm clear corneal incision. Ultrasound biomicroscopy
      (UBM) of the left eye revealed no missing or stretched zonular fibers extending
      from the ciliary body to the anterior capsule, a few iris root remnants, a normal
      ciliary body, an in-the-bag acrylic intraocular lens, and Descemet's membrane
      dehiscence at the corneal tunnel through which the iris extruded. The eye
      recovered 20/25 visual acuity after 1 week. Transient hyphema and a rise in
      intraocular pressure were recorded. This is the first report of traumatic
      aniridia 2 years after phacoemulsification with UBM evidence of undamaged zonular
      apparatus. A UBM examination may be clinically helpful, especially when blood
      prevents accurate slitlamp examination of the anterior segment.

PMID- 17010880
TI  - Dislocation of capsular bag with intraocular lens and capsular tension ring.
AB  - We report a case in which the capsular bag with an intraocular lens (IOL) and a
      capsular tension ring (CTR) dislocated into the vitreous. The dislocated foldable
      posterior chamber IOL and CTR were removed with a pars plana vitrectomy and
      exchanged with a scleral-fixated IOL. No complications occurred intraoperatively
      or postoperatively. Although insertion of a CTR decreases the risk for IOL
      dislocation, spontaneous capsular bag dehiscence can occur.

PMID- 17010881
TI  - Inadvertent stromal dissection during mechanical separation of the corneal
      epithelium using an epikeratome.
AB  - Epithelial flap complications occurred in 2 patients during epithelial separation
      using a Centurion SES epikeratome (Norwood Eye Care) in epi-laser in situ
      keratomileusis (LASIK). The complications consisted of stromal dissection at the
      margin of the pupil and an epithelial free cap including the superficial stroma.
      The epithelial flaps were repositioned without laser ablation. Three months
      postoperatively, the best corrected visual acuity in both patients was 20/20 and
      neither complained of visual discomfort. Slitlamp biomicroscopic examination
      showed that both corneas were completely healed with trace opacity, and
      topographic examinations revealed that irregularities in the stromal cutting
      sites were decreased. The patients had successful photorefractive keratectomy
      after complete healing of the dissected stroma. Stromal dissection during
      mechanical separation of the epithelium with an epikeratome is a potential
      complication of the epi-LASIK procedure, but proper management can result in good
      recovery without severe visual impairment.

PMID- 17010882
TI  - Persistent endocapsular hematoma following uneventful phacoemulsification and
      clear corneal incision cataract surgery.
AB  - We report the first case of persistent endocapsular hematoma following uneventful
      phacoemulsification and intraocular lens surgery through a clear corneal
      incision.

PMID- 17010883
TI  - Removal of lens epithelial cells to delay anterior capsule-intraocular lens
      adherence.
AB  - To test the theory that removing lens epithelial cells at the time of cataract
      extraction with intraocular lens (IOL) implantation or refractive lens exchange
      might decrease the rate at which the anterior capsule becomes adherent to the
      lens optic postoperatively, we performed the technique in approximately 200 eyes
      that were considered likely to require postoperative IOL exchange. In 4 eyes that
      had an IOL exchange procedure 6 to 12 weeks after the primary procedure, the
      anterior capsule was nonadherent or weakly adherent to the lens optic.

PMID- 17010884
TI  - Iris-cyst-simulating luxated lens.
AB  - A 2-month-old child was referred to our clinic for evaluation and management of a
      luxated lens. Under general anesthesia, an irregularly shaped iris was observed
      with the presence of a large iris cyst in the anterior chamber. Sector iridectomy
      with excision of the cyst was performed. Histopathologic examination confirmed
      the diagnosis of a stromal cyst of the iris. At the 3-year follow-up, there was
      no evidence of recurrence of the iris cyst or of a secondary cataract. This case
      report provides evidence that although a primary cyst of the iris stroma is
      uncommon, it should be considered in the differential diagnosis for an apparent
      lens luxation.

PMID- 17010885
TI  - Increased crystalline lens thickness and phacomorphic glaucoma in patients with
      Fanconi anemia.
AB  - We describe 2 siblings with Fanconi anemia (FA). One developed phacomorphic
      glaucoma, and both had increased crystalline lens thickness, features that have
      not been reported in patients with FA. The possible pathogenesis and clinical
      implications of the findings are discussed.

PMID- 17010886
TI  - Disappointment of patients on antidepressant therapy after excimer laser
      treatment.
AB  - We describe 2 patients who were receiving antidepressant therapy before excimer
      laser surgery, at the time of surgery, and after surgery. Both patients
      experienced the ocular side effects of antidepressant drugs, ie, symptoms due to
      dry eyes and mydriasis.

PMID- 17010887
TI  - Spontaneous nuclear fracture.

PMID- 17010888
TI  - Iris tears secondary to intraoperative floppy-iris syndrome associated with
      tamsulosin.

PMID- 17010889
TI  - Minimally invasive spine surgery. Preface.

PMID- 17010890
TI  - The development of minimally invasive spine surgery.
AB  - The modern era of minimally invasive spine surgery has its roots in percutaneous
      techniques developed in the mid-twentieth century. The widespread application of
      minimally invasive techniques seen today is predicated on technologic
      developments of only the past 10 years, however. This article reviews the
      development of minimally invasive spinal surgery as it has evolved for the
      cervical, thoracic, and lumbar spine. Each new development has sought to equal or
      improve on the effectiveness demonstrated by comparable open surgical techniques
      while reducing iatrogenic tissue trauma and resultant postoperative pain and
      disability, to produce overall better outcomes for patients.

PMID- 17010891
TI  - Endoscopic posterior cervical foraminotomy and discectomy.
AB  - Posterior cervical microendoscopic foraminotomy and discectomy is an effective
      minimally invasive approach to cervical radiculopathy caused by foraminal
      osteophytes or lateral disc herniations. This article reviews the technique in
      detail as well as the advantages over open approaches. Nuances of the technique,
      including complications and their management, are also explored.

PMID- 17010892
TI  - Minimally invasive cervical stenosis decompression.
AB  - Cervical stenosis and cervical spondylotic myelopathy are common disorders seen
      by many spine surgeons. Presentation can range from asymptomatic to myelopathy or
      myeloradiculopathy to lower extremity and gait problems attributed to lumbar
      disease. Various surgical procedures are practiced in the surgical management of
      this disease. Posterior cervical laminectomy is a familiar procedure and is the
      treatment of choice for multilevel disease. With the development of newer
      instruments and access devices, it has become possible to treat this problem
      through a minimally invasive approach.

PMID- 17010893
TI  - Minimally invasive posterior cervical arthrodesis and fixation.
AB  - This article describes the use of minimally invasive posterior cervical
      arthrodesis and internal fixation for the subaxial cervical spine. Such systems
      vary by the angulation of their screws and in the degree of the constraint placed
      at the screw-rod interface. The polyaxial tulip or islet connectors of the screws
      are able to angle medially, laterally, and straight, with varying degrees of
      rotational freedom in each direction, thus making segmental fixation more easily
      achievable from a top-loading approach and allowing for the possibility of
      minimally invasive posterior cervical fixation.

PMID- 17010894
TI  - Thoracic microendoscopic discectomy.
AB  - Thoracic microendoscopic discectomy is a safe effective treatment for surgical
      removal of herniated thoracic intervertebral discs. This approach allows access
      through a minimally invasive muscle-splitting posterolateral approach that does
      not place the contents of the thoracic cavity at risk. In the lumbar spine, this
      approach has been proven effective, with a shorter length of hospital stay, less
      postoperative pain, decreased blood loss, and shorter recovery time. These same
      advantages can be expected in the thoracic spine with appropriate patient
      selection and proper surgical technique.

PMID- 17010895
TI  - Thoracoscopy for correction of adult thoracic scoliosis.
AB  - The endoscopic technique of instrumentation, correction, and fusion for scoliosis
      has undergone radical modifications since the first surgery. Some key factors
      conducive to successful fusion, such as thorough discectomy and end plate
      removal, are common to endoscopic and non-endoscopic procedures. There are indeed
      special technical features in our endoscopic approach that clearly affect
      outcome, however, and their enumeration rightly chronicles the evolution of our
      experimental undertaking.

PMID- 17010896
TI  - Minimally invasive lumbar discectomy and foraminotomy.
AB  - This article provides an overview of a minimally invasive approach for lumbar
      discectomy and foraminotomy. The surgical technique is described in detail, and
      the current literature is reviewed to assess the clinical efficacy of the
      procedure.

PMID- 17010897
TI  - Minimally invasive lumbar decompression.
AB  - With the increasing elderly population, the number of patients presenting with
      symptoms secondary to lumbar stenosis can be expected to increase accordingly.
      Therefore, treatment of this disease process should become more prevalent, and
      the minimally invasive techniques offer another treatment option. As surgeons
      become more experienced in minimally invasive techniques, the reported advantages
      of the minimal access surgery, including reduction in soft tissue injury, less
      blood loss, shorter hospitalization, and faster recovery, should make this an
      attractive alternative to traditional open surgery. Continuing efforts in the
      minimally invasive field can be expected to yield new and potentially less
      invasive as well as possibly more efficacious treatment options in the future.

PMID- 17010898
TI  - Minimally invasive fusion and fixation techniques.
AB  - Instrumented fusion plays an important role in treating a variety of degenerative
      and traumatic diseases of the spine. Traditional open techniques have been
      associated with a high degree of approach-related morbidity because of muscle
      retraction and blood loss. A variety of minimally invasive techniques have been
      developed for instrumentation of the entire spine. Advances in our understanding
      of the cellular and molecular mechanisms for stable bony fusion should promote
      the use of even less invasive techniques in the future.

PMID- 17010899
TI  - Minimally invasive approaches to vertebral column and spinal cord tumors.
AB  - Minimally invasive approaches to spinal tumors have evolved rapidly over the past
      15 to 20 years as clinicians seek to avoid the morbidity and long-term
      dysfunction associated with traditional open surgical procedures. We review the
      noninvasive, percutaneous, and minimally invasive surgical techniques currently
      available for the treatment of spinal column and intradural spinal tumors,
      including minimal access thoracic corpectomy and minimal access intradural tumor
      surgery. The various advantages and limitations of these approaches as well as
      their appropriate indications and uses are also presented here. A measured
      understanding of surgical objectives and iatrogenic effects on patients' quality
      of life allows the surgeon to implement such minimally invasive approaches in the
      design of individualized treatment plans that range from pure palliation to
      definitive cure.

PMID- 17010900
TI  - Vertebroplasty and kyphoplasty.
AB  - Percutaneous vertebroplasty and kyphoplasty provide minimally invasive options
      for the management of osteoporotic and osteolytic vertebral compression
      fractures. These techniques provide substantial pain relief and support without
      requiring long periods of recumbency, and have an acceptable complication rate.
      Vertebral augmentation techniques such as vertebroplasty and kyphoplasty provide
      pain relief and improvement in quality of life in the highly selected patient.
      Complications can be avoided with careful surgical technique, and good outcomes
      can be achieved with proper patient selection.

PMID- 17010901
TI  - Innovative techniques in radiation therapy: editorial, overview, and crystal ball
      gaze to the future.

PMID- 17010902
TI  - Tomotherapy and other innovative IMRT delivery systems.
AB  - Fixed-field treatments, delivered using conventional clinical linear accelerators
      fitted with multileaf collimators, have rapidly become the standard form of
      intensity-modulated radiotherapy (IMRT). Several innovative nonstandard
      alternatives also exist, for which delivery and treatment planning systems are
      now commercially available. Three of these nonstandard IMRT approaches are
      reviewed here: tomotherapy, robotic linear accelerators (CyberKnife, Accuray
      Inc., Sunnyvale, CA), and standard linear accelerators modulated by jaws alone or
      by their jaws acting together with a tertiary beam-masking device. Rationales for
      the nonstandard IMRT approaches are discussed, and elements of their delivery
      system designs are briefly described. Differences between fixed-field IMRT dose
      distributions and the distributions that can be delivered by using the
      nonstandard technologies are outlined. Because conventional linear accelerators
      are finely honed machines, innovative design enhancement of one aspect of system
      performance often limits another facet of machine capability. Consequently the
      various delivery systems may prove optimal for different types of treatment, with
      specific machine designs excelling for disease sites with specific target volume
      and normal structure topologies. However it is likely that the delivery systems
      will be distinguished not just by the optimality of the dose distributions they
      deliver, but also by factors such as the efficiency of their treatment process,
      the integration of their onboard imaging systems into that process, and their
      ability to measure and minimize or compensate for target movement, including the
      effects of respiratory motion.

PMID- 17010903
TI  - Innovative technologies in radiation therapy: brachytherapy.
AB  - Brachytherapy has changed dramatically in the last decade, with the widespread
      introduction of high-dose rate afterloading systems having greater flexibility of
      source loading patterns and smaller sources enabling new anatomic sites to be
      considered. This has been harnessed to the major developments in cross-sectional
      imaging and dosimetry planning systems to enable highly conformal radiotherapy to
      be delivered accurately and reliably by brachytherapy. There has been a major
      change in the distribution of sites treated, the majority being prostate,
      gynecologic, and breast treatments, whereas an emerging role as a simple but
      effective palliative treatment in bronchus, esophagus, and rectal cancers has
      also been recognized.

PMID- 17010904
TI  - Alternative methods for intensity-modulated radiation therapy inverse planning
      and dose delivery.
AB  - A large number of IMRT systems are currently being marketed. Many of these
      systems appear to be unique, and manufacturers often emphasize design differences
      as they argue the merits of their particular approach. This paper focuses on
      highlighting the underlying feature that is intrinsically part of all IMRT
      systems. On the other hand, major differences often appear at the implementation
      stage for dose delivery. Such variations are evident because each manufacturer
      has a unique approach to balancing the issues of treatment time, leakage
      radiation reaching the patient's total body, aperture approximation of the ideal
      intensity maps, increasing the angles of approach for the treatment fields,
      integration of on-line imaging, selection of treatment distance, availability of
      different photon energies, and overall system complexity (i.e., cost). How these
      different issues are handled in the process of system design affects the relative
      advantages and disadvantages that appear in the final product. This paper takes
      the approach of dividing the various IMRT methods into categories that are
      divided roughly along the lines of the technique used during dose delivery to
      approximate the intensity patterns. Other features of each system are included
      under these sub-sections.

PMID- 17010905
TI  - The clinical application of intensity-modulated radiation therapy.
AB  - Intensity-modulated radiation therapy is a delivery system that, when coupled
      with a treatment-planning optimization system, presents the opportunity to
      conform the dose to the target better than 3-dimensional conformal therapy,
      particularly in the case of concave targets. Appropriate clinical applications of
      this technology to challenging patient treatment scenarios requires careful
      consideration of issues related to target volume-dose heterogeneity and the
      influence of patient setup uncertainties. These issues are reviewed and
      illustrated. To date, clinical reports of these treatments for prostate and head
      and neck cancers have the most mature data. Those results are summarized here.
      Future applications of this technology can be expected to take careful,
      considered advantage of this technology to further rearrange dose distributions
      across target volumes to produce an integrated overall gain in treatment
      objectives. However, these innovative applications need to be approached with
      caution, preferably in prospective clinical trials that would help determine if
      the hypothetical clinical benefits are in fact realizable.

PMID- 17010906
TI  - Is PET-based treatment planning the new standard in modern radiotherapy? The head
      and neck paradigm.
AB  - The use of positron-emission tomography (PET) in the treatment planning process
      has become more and more popular over the years, although important questions
      such as how, when, and for which clinical benefit have never been answered. In
      this framework, the objective of this article is to review the evidence
      supporting the use of PET in radiotherapy treatment planning, with special
      emphasis on its application for head and neck tumors. The use of positron-labeled
      fluorodeoxyglucose for target volume selection should be discussed in terms of
      sensitivity and specificity in comparison with typical anatomic imaging
      modalities. It will not be of similar utility across all tumor sites. The use of
      PET for target volume delineation requires specific tuning of parameters such as
      image acquisition, processing, and segmentation, and this may vary from one tumor
      site to another. Molecular imaging with other tracers and "theragnostic" are in
      the pipeline, but how much the patient will gain from it and how these advances
      should be implemented in routine clinical practice are unresolved questions.
      Therefore, although integration of PET images into the radiotherapy process seems
      promising, for the moment it should remain in the research arena.

PMID- 17010907
TI  - Radiotherapy of mobile tumors.
AB  - In this overview, we discuss some major issues related to the management of
      mobile tumors and gating in radiotherapy. For most types of organ motion, there
      are both interfraction and intrafraction components. For respiratory motion, the
      magnitudes of these 2 components can be comparable and therefore both should be
      handled carefully. The motion artifacts in computed tomography (CT) simulation
      are discussed and the 4-dimensional CT scan technique is recommended for
      treatment simulation of patients with mobile tumors. There are various methods
      for handling organ motion in treatment delivery. Caution should be exercised when
      using patient-specific motion information for treatment planning because motion
      characteristics may vary from the treatment simulation time to the treatment
      delivery sessions. Respiratory gating is potentially accurate, easy to implement,
      and may be widely adopted in clinical practice in the near future, if existing
      technical problems can be resolved.

PMID- 17010908
TI  - Radiation therapy with charged particles.
AB  - Charged particle beams can offer an improved dose conformation to the target
      volume as compared with photon radiotherapy, with better sparing of normal tissue
      structures close to the target. In addition, beams of ions heavier than (4)He
      exhibit a strong increase of the linear energy transfer in the Bragg peak as
      compared with the entrance region. These physical and biological properties are
      much more favorable than in photon radiotherapy. As a consequence, particle
      therapy with protons and heavy ions has gained increasing interest worldwide, and
      many clinical centers are considering introducing radiation therapy with charged
      particles. This contribution summarizes the physical and technical principles of
      charged particle therapy with protons and heavy ions. It briefly reviews the
      clinical experience gathered so far with proton therapy and gives a more detailed
      summary of the recent results in carbon ion therapy of skull base tumors, head
      and neck tumors, non-small-cell lung cancer, hepatocellular carcinomas, bone and
      soft-tissue sarcomas, and prostate cancer.

PMID- 17010909
TI  - The atlas of complication incidence: a proposal for a new standard for reporting
      the results of radiotherapy protocols.
AB  - We present a new method of reporting the results of radiotherapy protocols. The
      dose-volume atlas of complication incidence is a comprehensive and unbiased
      summary of the dose-volume exposures and complications occurring in patients
      after treatment. This new tool provides clear and systematic information about
      the safety of regions of dose-volume exposure previously treated that can be used
      when considering new treatments. Actuarial and model-dependent versions of the
      atlas are described. By using the raw data in the appropriate forms of the atlas,
      logistic regression, Kaplan-Meier, and Cox proportional hazards analysis can be
      performed, allowing for the independent calculation of dose-volume response. The
      data required are simple enough that provided compatible definitions of dose,
      volume, and complications are used, atlases from different protocols are
      potentially additive, facilitating the meta-analysis of inter-interinstitutional
      data. If this method were adopted as a standard for reporting the outcome of
      treatment protocols, a potentially synergistic increase in the utility of each
      protocol could result.

PMID- 17010911
TI  - Primary charge motions and light-energy transduction in bacteriorhodopsin.
AB  - The bacteriorhodopsin protein (bR) in the cell membrane of Halobacterium halobium
      is a light driven proton pump. Many details are known about its structure and the
      molecular mechanism of proton translocation. The events may be characterized by:
      (1) the changes in light absorption after photon excitation (the photocycle); (2)
      the charge motion cycle inside the protein: the steps taken by the proton during
      translocation; (3) the retinal cycle. changes in isomerization and protonation;
      and (4) the opsin cycle: alterations of protonation of different amino acids in
      the apoprotein. From a review of existing data a more or less concise picture of
      the parallelism of the above four cycles emerges, which may be valuable as a
      model for understanding other types of molecular pumps.

PMID- 17010912
TI  - Signal perception and amplification in photoresponses of cyanobacteria.
AB  - In addition to a number of other external stimuli, the gliding cyanobacterium,
      Phormidium uncinatum, uses light as a clue to control movement in order to find
      and stay in a microhabitat with optimal conditions for growth and survival of the
      population. Of the three photoresponses developed in cyanobacteria, phototaxis,
      photokinesis and photophobic responses, the latter are the most prominent for
      this task. Step-down phobic responses are mediated by the photosynthetic pigments
      and are linked to the linear electron-transport chain. A change in the fluence
      rate is reflected by a change in the proton-motive force which is amplifi.

PMID- 17010913
TI  - Dependence of some conformational properties of polyglycine on composition and
      sequence of secondary structure.
AB  - The values of four conformational properties, unperturbed dimensions <r2>0,
      dipole moment <mu2>, mean squared optical anisotropy <gamma2> and molar Kerr
      constant <mK> have been calculated for polyglycine chains of x = 100 repeat units
      with varying composition of alpha-helix, beta-sheet and random coil
      conformations. The influence of the conformational sequence on these properties
      has been investigated by calculating the four above-mentioned properties together
      with the end-to-end vector for several polyglycine oligomers.

PMID- 17010914
TI  - Membrane potential and Donnan potential.
AB  - The Nernst-Planck-Poisson equations for the potential profile across a membrane
      are exactly solved without recourse to the assumption of constant field within
      the membrane. It is assumed that the membrane core of thickness dc is covered by
      a surface layer of thickness ds in which the membrane-fixed charges are
      distributed at a uniform density N. The membrane boundary potentials as well as
      the diffusion potentials contribute to the membrane potential. It is shown that
      for ds greater or similar 1/k, k being the Debye-Huckel parameter, the potential
      in the membrane surface layer except in the region very near the
      membrane/solution boundary is effectively equal to the Donnan potential and that
      its contribution to the membrane potential becomes dominant as N increases. For
      low N, on the other hand, the membrane potential arises mostly from the diffusion
      potential.

PMID- 17010915
TI  - Hydration of nucleic bases in dilute aqueous solutions. Apparent molar adiabatic
      and isothermal compressibilities, apparent molar volumes and their temperature
      slopes at 25 degrees C.
AB  - The concentration increment of the ultrasound velocity has been measured with an
      accuracy of +/- 0.03 cm/s in dilute aqueous solutions of a variety of nucleic
      bases and their derivatives in the concentration range 0.5-1.5 mg/g H2O at
      temperatures of 15-35 degrees C. A new method for the precise measurement of
      ultrasound velocity in small volumes of liquids has been used. The values of the
      apparent molar adiabatic compressibilities plus the corresponding temperature
      slopes, apparent molar volumes with their temperature slopes, and apparent molar
      isothermal compressibilities at infinite dilution have been obtained. The
      regularities describing the signs of these values and their dependence on the
      chemical structure of the solute have been revealed. It is shown that these
      regularities can be described as a consequence of partial 'normalization' of some
      of the properties of water around the bases, namely, weaker structural
      contribution to compressibility, less negative temperature slope of
      compressibility and less negative structural contribution to the coefficient of
      thermal expansion of water.

PMID- 17010916
TI  - Resonance Raman spectra of chlorophylls dissolved in liquid crystal matrices. II.
      Order parameters of chlorophyll a in an MBBA + EBBA liquid crystalline mixture.
AB  - The molecular ordering of molecules embedded in a uniaxial liquid crystalline
      system has been considered. In particular, planar Chl a molecules in an MBBA +
      EBBA mixture have been studied by using polarized resonance Raman spectroscopy.
      The second- and fourth-rank order parameters and the orientational distribution
      function of Chl a in the nematic MBBA + EBBA liquid crystalline phase are
      discussed.

PMID- 17010918
TI  - Denaturation of bacteriorhodopsin by organic solvents.
AB  - The denaturation of bacteriorhodopsin by various organic solvents was studied
      using absorption, circular dichroism (CD) and fluorescence measurements. Organic
      solvents with a hydrogen-bonding group caused the release of retinal. The CD
      measurements showed that the helical structure was maintained even in the
      denatured state, whereas its tertiary structure was destroyed. The change in
      fluorescence intensity of tryptophan and fluorescent retinal also confirmed that
      the tertiary structure was destroyed. Comparison of the denaturation efficiency
      of various organic solvents showed that the concentration at denaturation was
      inversely proportional to the partition coefficient of the denaturant. This
      inverse proportionality clearly indicated that denaturation was determined by the
      concentration of denaturants which partitioned into the hydrophobic region of the
      membrane. It was discussed from the experimental results that the tertiary
      structure of bacteriorhodopsin was stabilized by the hydrogen-bonding networks
      between side chains of the helices. The results obtained from analysis of the
      amino acid sequence were also consistent with the hydrogen-bonding mechanism for
      the formation of the tertiary structure.

PMID- 17010919
TI  - Charge-transfer complexes of plastoquinone and alpha-tocopherol quinone in vitro.
AB  - It has been found that plastoquinone (PQ) and alpha-tocopherol quinone (alpha-TQ)
      can form quinhydrone-type charge-transfer complexes on PQH2 and alpha-TQH2,
      respectively, both in the crystalline state and in solutions of organic solvents.
      The charge-transfer spectra of PQ/PQH2 mixtures in hydrophobic solvents showed
      two bands: one at 349-358 nm, the other at 430-440 nm, one charge-transfer band
      at 351-355 nm occurring in water-miscible solvents. The intensity ratio of these
      two bands varied with changing PQ/PQH2 ratio. The charge-transfer spectra of
      alpha-TQ/alpha-TQH2 mixtures in all solvents investigated showed one peak at 361
      367 nm and a broad shoulder within the range 400-540 nm, whose shape varied
      depending on the solvent used. In the infrared spectrum of PQ and alpha-TQ (1700
      1600 cm(-1)) splitting of the carbonyl band occurred and was caused by the
      presence of two peak. In the spectra of quinhydrones the splitting disappeared,
      this being brought about by the appearance of a new peak at the position of
      splitting, which originated from the complexed quinones. The possibility of the
      formation of such complexes in thylakoid membranes is discussed.

PMID- 17010921
TI  - The mean conformation of N-acetylamino acid N'-methylamides in dimethyl sulfoxide
      solution.
AB  - The mean conformation of a series of N-acetylamino acid N'-methylamides in
      dimethyl sulfoxide (DMSO) was determined by 1H-NMR and 13C-NMR methods. The
      series investigated consisted of derivatives of DL-Ala, DL-Asn, Gln, His, DL-Ile,
      DL-Leu, Met, DL-Pro, DL-Phe, Ser, Thr, Trp, Tyr, DL-Val, DL-Nva, and dl-Nle. It
      was found that the conformational equilibria in DMSO are dominated by C5 and C7eq
      forms. The amounts of these forms in the equibbria were found to be roughly
      proportional to the Boltzmann probabilities for the occurrence of a definite
      form, as calculated theoretically by Vasquez et al.(Macromolecules 16 (1983)
      1043). Exceptions to this rule were DL-Pro and, to a lesser extent, Ser, Asn and
      Trp derivatives.

PMID- 17010922
TI  - Gibbs free energy of transfer of glycine and diglycine from water to alkylurea
      solutions. Measured vs. calculated values.
AB  - Ternary systems comprising water (1), glycine (diglycine) (2) and alkylurea (3)
      have been investigated using vapor pressure osmometry. Equations were obtained in
      terms of the molalities of the solutes for the activity coefficients of glycine
      and diglycine in these systems. The alkylureas used were methyl-, ethyl- and N,
      N'-dimethylurea. Using the activity coefficients the Gibbs free energy of
      transfer at infinite dilution of component 2 from water to alkylurea solutions
      was determined. Since the enthalpies of transfer are known, the corresponding
      entropies could also be obtained. Calculation of the Gibbs free energy of
      transfer at infinite dilution of component 2 rests on the assumption that it can
      be divided into two parts: the difference between the Gibbs free energy of cavity
      formation and that of interaction in the alkylurea solution and water,
      respectively. The first part was calculated by scaled particle theory using
      experimental density and surface tension data. The second part was taken to be
      due mainly to the change in dipole-dipole interactions.

PMID- 17010923
TI  - A new model of counterion condensation in polyelectrolyte solutions. III.
      Theoretical predictions of competitive condensation between counterions of
      different valences.
AB  - Our model has been extended for theoretical estimation of competitive
      condensation of counterions of different valences onto polyelectrolytes in
      solution. The estimations are compared with those obtained from Manning theory
      and with experimental data on counterion activity coefficients. The agreement
      with the data for sodium polystyrenesulfonate/MgCl2, CaCl2 is satisfactory.

PMID- 17010924
TI  - Physicochemical properties of charge-transfer complexes of plastoquinone and
      alpha-tocopherol quinone, and their possible role in vivo.
AB  - It has been found that the solubility of PQH2 and alpha-TQH2 in hexane increased
      with the increase in PQ and alpha-TQ concentrations, respectively, that is
      connected with the formation of quinhydrone-type charge-transfer complexes.
      Measurements of the solubility of both prenylquinones and their reduced forms in
      hexane and acetone, at -30 degrees C and room temperature, showed a much higher
      affinity of the quinol forms for acetone than for hexane. In the case of
      quinones, the difference in affinity was not significant. The possibility of
      charge-transfer complex formation by PQ and alpha-TQ in thylakoid membranes and
      the influence of such complexes on the diffusion of PQH2 and alpha-TQH2 molecules
      have been considered.

PMID- 17010925
TI  - Resonance Raman spectra of chlorophylls dissolved in liquid crystal matrices.
      III. Orientational distribution function of chlorophyll b in an MBBA + EBBA
      liquid crystalline matrix.
AB  - Polarized resonance Raman spectra of chlorophyll (Chl) b oriented in a mixture of
      p-methoxybenzylideno-p'-butylaniline (MBBA) and p-ethoxybenzylideno-p'
      butylaniline (EBBA) have been measured. The spectra have been analyzed and the
      second- and fourth-rank order parameters and the orientational distribution
      function of Chl b are presented.

PMID- 17010926
TI  - Growth and electric current loops in plants.
AB  - A theory is presented for a relationship between ion accumulation and electric
      current loops in multicellular systems such as the roots and stems of higher
      plants. A network of electric circuits shows that the electric current
      transported across the cell membrane flows between an elongating region and a
      mature region, not only in roots but also in stems. In roots, ions constituting
      the extracellular electric current flow in the external aqueous medium, while in
      stems an electric current of comparable density flows within the epidermal cell
      wall. Based on this theoretical result, electric isolation between the elongating
      and mature regions was made in the case of both roots and stems. The speed of
      growth during the initial stage was greatly decreased due to a change in the
      distribution of protons around the surfaces of the plant by cutting off the
      electric current loop. Electrochemical calculation shows that ions are not always
      accumulated at the efflux site, since the ion distribution is strongly affected
      by the relation of the magnitudes between the electric field and electric
      current. The results calculated for the electric potential and pH distributions
      around the root agree with experimental data.

PMID- 17010927
TI  - A plant-based repellent protects against Tunga penetrans infestation and sand
      flea disease.
AB  - Tungiasis is a parasitic skin disease prevalent in impoverished populations in
      the tropics and associated with considerable morbidity. Treatment options are
      limited and prophylaxis has never been attempted. We assessed the effectiveness
      of a plant-based repellent to prevent infestation with Tunga penetrans and sand
      flea disease in an urban squatter settlement in Fortaleza, Northeast Brazil. Two
      cohorts were formed. One cohort started with the intervention while another
      served as control. The plant-based repellent Zanzarin was applied twice daily on
      the skin of the feet. After 4 weeks and a wash-out-phase of another 2 weeks,
      cross-over was performed. Study members were examined twice per week for the
      presence of newly embedded sand fleas. The number of viable and dead sand fleas
      and the total number of sand flea lesions were determined. Sentinel rats were
      used to assess local transmission dynamics. Outcome measures were the number of
      newly embedded sand fleas per individual per day, number of sand flea lesions per
      individual according to the stage, as well as type and degree of clinical
      pathology. Zanzarin applied twice daily on the feet reduced the number of newly
      embedded fleas by 92% (interquartile range 81-100%), the total number of lesions
      by 87% (81-98%) and reversed tungiasis-associated clinical pathology almost
      completely. In conclusion, in a setting in which tungiasis is an important health
      threat, the daily application of a plant-based repellent prevented the
      infestation with T. penetrans and sand flea disease.

PMID- 17010928
TI  - Precise and comparative pegylation analysis by microfluidics and mass
      spectrometry.
AB  - Standard SDS-PAGE analysis of a pegylated protein was able to confirm an increase
      in its molecular size after reaction with an activated polyethylene glycol (PEG)
      but could do little to identify the extent of pegylation or to support
      characterization of the consistency of the modified protein. In this article, we
      demonstrate the utility of the capillary electrophoresis technology (using a
      microfluidic system) in analyzing the pegylation pattern of a recombinant protein
      over a range of 1-12 PEGs per polypeptide. Confirmatory data from mass
      spectrometry analysis of pegylated adducts are also presented. These allowed
      independent confirmation of the extent of pegylation. This electrophoretic
      analysis gives a robust, reproducible, and direct characterization of PEG
      adducts. We found that traditional estimation of PEG adducts by an indirect
      colorimetric (trinitrobenzene sulfonic acid) reaction, which detects loss of free
      amino groups, was quite erroneous for the recombinant protein in our study as
      well as several commercially available pegylated proteins. These results support
      the use of this capillary electrophoresis device for precise characterization of
      pegylated proteins.

PMID- 17010929
TI  - [Results of resection of locally recurrent rectal cancer].
AB  - AIMS OF THE STUDY: The treatment of locally recurrent rectal cancer (LRRC)
      remains a difficult and controversial issue. The aim of this study was to
      retrospectively assess the results of an univocal attitude associating resection
      of a priori resectable lesions using visceral excisions as required, without
      sacral excision, but including intra-operative radiotherapy (IORT). PATIENTS AND
      METHODS: Between 1989 and 1999, 32 patients underwent resection for LRRC. Twelve
      had previously undergone abdomino-perineal excision and 22 had received
      radiotherapy. Twenty-three patients underwent pelvic exenteration (total in 17,
      with rectus myocutaneous flap in 18). Twenty-five patients underwent IORT.
      RESULTS: Three patients (9.3%) died in the early postoperative period and 11
      experienced complications (37%). Resections were considered R0 in 6 patients, R1
      in 21 patients and R2 in 5 patients. Five-year survival rates, overall and
      without disability, were respectively 12%, 12% and 5%. Median survivals, overall
      and without disability, were respectively 22 and 12 months. CONCLUSION: Resection
      of LRRC remains a surgical challenge. It may achieve an average of one-year
      survival without disability, and hope for a few cures. Improvement of oncologic
      results might come from a more accurate patient selection.

PMID- 17010930
TI  - Study of calix[4]resorcinarene-dopamine complexation in mixed phospholipid
      monolayers formed at the air-water interface.
AB  - We have studied the physical properties of monolayers formed by
      calix[4]resorcinarene and in mixtures with dipalmitoyl phosphatidylcholine (DPPC)
      in various molar ratios formed at the air-water interface and at presence of
      dopamine in water subphase by means of measurements of surface pressure and
      dipole potential. We showed that both calix[4]resorcinarene as well as its
      mixture with DPPC form stable monolayers at the water subphase. The presence of
      dopamine resulted in an increase of the mean molecular area and in a decrease of
      the compressibility modulus of the monolayers. For mixed monolayers at higher
      content of calix[4]resorcinarene (> 0.2 molar fraction) a deviation from ideal
      miscibility took place especially for monolayers in a solid state. This can be
      connected with formation of aggregates of calix[4] resorcinarene. Lowest
      miscibility and weakest interaction of dopamine with a monolayer was observed for
      calix[4]resorcinarene molar fraction of 0.33 in the monolayer.

PMID- 17010931
TI  - Neuropsychological effects of stress on social phobia with and without comorbid
      depression.
AB  - BACKGROUND: The influence of stress on neuropsychological functioning was
      assessed in socially phobic (SP), comorbid socially phobic/major depression (CM),
      and asymptomatic control subjects (AC) under baseline and stressor conditions.
      METHODS: Subjects were 33 clinically diagnosed undergraduates aged 18 to 41
      years. Neuropsychological measures included the Trail Making Test, Wisconsin Card
      Sorting Test (WCST), Spatial Span, and Digit Span administered during a baseline
      condition and a psychosocial stress condition (videotaping). RESULTS: Spatial
      Span scores were reduced for SP during stress, improved for AC, and showed no
      change for CM. TMT B times showed an interaction effect, with completion time
      improving significantly less for SP than for AC and CM during stress. Analyses of
      the normative data for WCST total errors indicated that AC and CM improved
      significantly during stress, while SP performance declined during stress.
      CONCLUSIONS: The present findings suggest that comorbid depressed versus non
      depressed SP subjects respond uniquely to stress in terms of their
      neuropsychological functioning and self-reported mood and experiences;
      generalized social phobia may be associated with spatial working memory
      disturbance during social stress. Therefore, situations involving potential
      social and personal evaluation (e.g., examinations or presentations) may have a
      significant impact on the neuropsychological functioning of SP individuals.

PMID- 17010932
TI  - Generalized expectancies for negative mood regulation predict change in anxiety
      and depression among college students.
AB  - Negative mood regulation (NMR) expectancies, or the beliefs held by individuals
      that, when faced with various manifestations of stress and negative affect, they
      can successfully cope with such mood states, have proven to be a most useful
      construct in the context of better understanding self-regulatory processes. In
      the present prospective study, we examined the predictive utility of NMR
      expectancies with respect to its ability to predict residual change in both
      depressive and anxiety symptoms over an 8-week timeframe in a sample of 322
      college students. Initial correlational analyses revealed that, as anticipated,
      NMR expectancies were negatively correlated with depressive and anxiety
      symptomatology, as well as with maladaptive coping style. Conversely, NMR
      expectancies were positively associated with self-reported adaptive coping. A
      series of hierarchical regression analyses revealed that, even when controlling
      for age, sex, baseline levels of affective distress (depression or anxiety), and
      coping styles, NMR expectancies predicted change in both depressive and anxiety
      symptomatology. Implications of the findings pertinent to theory building and
      testing are discussed.

PMID- 17010933
TI  - Expression profiling characterization of laminin alpha-2 positive MDC.
AB  - In the Caucasian population, patients affected by the most frequent forms of
      congenital muscular dystrophies (MDC) are commonly divided into two groups. The
      first is characterized by mutations of the gene for the laminin alpha-2 (LAMA2).
      The second is positive for this protein, highly heterogeneous, and has no
      specific genetic defect associated yet. We studied the skeletal muscle
      transcriptome of four LAMA2 deficient and six LAMA2 positive MDC patients by cDNA
      microarrays. The expression profiling defined two patients groups: one mild and
      one severe phenotype. This result was in agreement with histopathological
      features but only partially with the clinical classification. The mild phenotype
      is characterized by a delayed maturation from slow to fast muscle fibers. Other
      muscle transcripts, such as telethonin, myosin light-chains 3 and 1V, are
      underexpressed in this group. We suggest that expression profiling will provide
      important information to improve our understanding of the molecular basis of
      laminin alpha-2 positive MDC.

PMID- 17010934
TI  - Transcriptional regulation of the human TR2 orphan receptor gene by nuclear
      factor 1-A.
AB  - The human testicular receptor 2 (TR2), a member of the nuclear hormone receptor
      superfamily, has no identified ligand yet. Previous evidence demonstrated that a
      63bp DNA fragment, named the promoter activating cis-element (PACE), has been
      identified as a positive regulatory region in the 5' promoter region of the human
      TR2 gene. In the present report, the human nuclear factor 1-A (NF1-A) was
      identified as a transcriptional activator to recognize the center of the PACE,
      called the PACE-C. NF1-A could bind to the 18bp PACE-C region, and enhance about
      13- to 17-fold of the luciferase reporter gene activity via the PACE-C in dose
      dependent and orientation-independent manners. This transcriptional activation
      was further confirmed by real-time RT-PCR assay. In conclusion, our results
      indicated that NF1-A transcription factor plays an important role in the
      transcriptional activation of the TR2 gene expression via the PACE-C in the
      minimal promoter region.

PMID- 17010935
TI  - Structural and functional properties of lengsin, a pseudo-glutamine synthetase in
      the transparent human lens.
AB  - Lengsin (LGS) is an abundant transcript in the human lens, encoding a predicted
      polypeptide similar to glutamine synthetase (GS). We show that a major
      alternatively spliced product of LGS codes for a 57kDa polypeptide that assembles
      into a catalytically inactive dodecamer, cross-reacts with anti-GS antibodies,
      and is expressed at high levels in transparent, but not cataractous, human
      lenses. Based on this characteristic oligomeric organization, preferential
      expression in the transparent lens, and amyloid-beta association previously
      reported for GS, a potential chaperone-like role of LGS has been investigated. We
      find that LGS has six binding sites for the hydrophobic surface probe bis-ANS and
      relieves cellular toxicity caused by amyloid-beta expression in a folding
      impaired yeast mutant. While documenting the structural similarity between LGS
      and prokaryotic GS-I, the data rule out any involvement of lengsin in glutamine
      biosynthesis and suggest an unrelated role that may be important for lens
      homeostasis and transparency.

PMID- 17010936
TI  - Genetic reassortment of infectious bursal disease virus in nature.
AB  - Infectious bursal disease virus (IBDV), a double-stranded RNA virus, is a member
      of the Birnaviridae family. Four pathotypes of IBDV, attenuated, virulent,
      antigenic variant, and very virulent (vvIBDV), have been identified. We isolated
      and characterized the genomic reassortant IBDV strain ZJ2000 from severe field
      outbreaks in commercial flocks. Full-length genomic sequence analysis showed that
      ZJ2000 is a natural genetic reassortant virus with segments A and B derived from
      attenuated and very virulent strains of IBDV, respectively. ZJ2000 exhibited
      delayed replication kinetics as compared to attenuated strains. However, ZJ2000
      was pathogenic to specific pathogen free (SPF) chickens and chicken embryos.
      Similar to a standard virulent IBDV strain, ZJ2000 caused 26.7% mortality, 100%
      morbidity, and severe bursal lesions at both gross and histopathological levels.
      Taken together, our data provide direct evidence for genetic reassortment of IBDV
      in nature, which may play an important role in the evolution, virulence, and host
      range of IBDV. Our data also suggest that VP2 is not the sole determinant of IBDV
      virulence, and that the RNA-dependent RNA polymerase protein, VP1, may play an
      important role in IBDV virulence. The discovery of reassortant viruses in nature
      suggests an additional risk of using live IBDV vaccines, which could act as
      genetic donors for genome reassortment.

PMID- 17010937
TI  - Loss of HB-EGF in smooth muscle or endothelial cell lineages causes heart
      malformation.
AB  - Epidermal growth factor (EGF) and ErbB family molecules play a role in heart
      development and function. To investigate the role of EGF family member, heparin
      binding EGF-like growth factor (HB-EGF) in heart development, smooth muscle and
      endothelial cell lineage-specific HB-EGF knockout mice were generated using the
      Cre/loxP system in combination with the SM22alpha or TIE2 promoter. HB-EGF
      knockout mice displayed enlarged heart valves, and over half of these mice died
      during the first postnatal week, while survivors showed cardiac hypertrophy.
      These results suggest that expression of HB-EGF in smooth muscle and/or
      endothelial cell lineages is essential for proper heart development and function
      in mice.

PMID- 17010938
TI  - RILP interacts with VPS22 and VPS36 of ESCRT-II and regulates their membrane
      recruitment.
AB  - RILP is emerging as a key regulator of late endocytic pathway by functioning as a
      downstream effector of activated Rab7 and Rab34, while ESCRT-I-->ESCRT-II-->ESCRT
      III machinery acts in sorting proteins to the multivesicular body (MVB) initiated
      at the early/sorting endosome. We show here that the early machinery is
      integrated with the late machinery through a novel regulatory loop in which RILP
      interacts with VPS22 and VPS36 of ESCRT-II to mediate their membrane recruitment.
      The N-terminal and C-terminal half of RILP mediate interaction with VPS22 and
      VPS36, respectively. Overexpression of RILP leads to enlarged and clustered MVBs
      marked by lysobisphosphatidic acid (LBPA). In addition, RILP or its C-terminal
      fragment causes a retardation of sorting internalized EGF to the degradation
      route at the level of sorting endosomes marked by EEA1. We propose that RILP-
      >ESCRT-II serves as a regulatory/feedback loop to govern the coordination of
      early and late parts of the endocytic pathway.

PMID- 17010939
TI  - Allodynia and hyperalgesia suppression by a novel analgesic in experimental
      neuropathic pain.
AB  - SCP-1, n-[alpha-(benzisothiazol-3(2ho-ona,1-dioxide-2yl)-acetyl]-p-aminophenol
      (100 nmol), when intrathecally injected, suppressed tactile allodynia and thermal
      hyperalgesia in a rat neuropathic pain model. The tactile allodynia suppression
      lasted for at least 4h and SCP-M1 (100 nmol), the main metabolite of SCP-1,
      displayed similar suppression as SCP-1, but shorter latency, indicating SCP-M1
      may be the bioactive component of SCP-1. Acetaminophen was less potent than SCP-1
      and SCP-M1. To study mechanisms underlying SCP-1 action, we recorded voltage
      gated Ca(2+) channel currents in acutely isolated dorsal root ganglion neurons
      using the whole-cell patch-clamp technique. SCP-1 and SCP-M1 inhibited non-L-type
      calcium channel currents up to 23.0+/-2.3% and 23.1+/-3.5%, respectively, at a
      depolarized pulse to -10 mV from a holding potential of -80 mV. Acetaminophen
      only induced 6.8+/-1.0% inhibition. The results suggest SCP-1 possesses anti
      nociceptive activity in the rat model involving calcium channel blocking
      properties.

PMID- 17010940
TI  - PPARgamma agonists prevent TGFbeta1/Smad3-signaling in human hepatic stellate
      cells.
AB  - PPARgamma agonists inhibit liver fibrosis, but the mechanisms involved are
      uncertain. We hypothesized that PPARgamma agonists inhibit transforming growth
      factor (TGF)beta1-activation of TGFbeta receptor (TGFbetaR)-1 signaling in
      quiescent stellate cells, thereby abrogating Smad3-dependent induction of
      extracellular matrix (ECM) genes, such as PAI-1 and collagen-1alphaI. To test
      this, human HSC were cultured to induce a quiescent phenotype, characterized by
      lipid accumulation and PPARgamma expression and transcriptional activity. These
      adipocytic HSC were then treated with TGFbeta1+/-a TGFbetaR-1 kinase inhibitor
      (SB431542) or a PPARgamma agonist (GW7845). TGFbeta1 caused dose- and time
      dependent increases in Smad3 phosphorylation, followed by induction of collagen
      and PAI-1 expression. Like the TGFbetaR-1 kinase inhibitor, the PPARgamma agonist
      caused dose-dependent inhibition of all of these responses without effecting HSC
      proliferation or viability. Thus, the anti-fibrotic actions of PPARgamma agonists
      reflect their ability to inhibit TGFbeta1-TGFbetaR1 signaling that initiates ECM
      gene expression in quiescent HSC.

PMID- 17010941
TI  - MnSOD marks cord blood late outgrowth endothelial cells and accompanies robust
      resistance to oxidative stress.
AB  - Cord blood is source of colony-forming progenitors to vascular endothelial cells
      for potential use in cell therapies. These cells-called blood late outgrowth
      endothelial cells (OECs)-have undergone endothelial differentiation, but appear
      to still possess functional properties different from mature endothelial cells. A
      large-scale comparative proteomics screen of cord blood OECs versus human vein
      endothelial cells (HUVECs) using two-dimensional gel electrophoresis and mass
      spectrometry identified specific expression of manganese superoxide dismutase
      (MnSOD), a key antioxidant enzyme expressed in the mitochondria, in OECs but not
      in HUVECs. Immunoblotting verified significant MnSOD levels in all OEC isolates
      tested and maintained throughout passaging. Endothelial function and cell
      survival/proliferation assays in the presence of high cytotoxic doses of the
      superoxide generator compound LY83583 showed OECs profoundly better protected
      against oxidative stress than HUVECs. Such cytoprotective levels of MnSOD cells
      could give therapeutic cell transplants a survival advantage in necrotic or
      ischemic conditions.

PMID- 17010942
TI  - Cloning of a cDNA encoding a novel marmoset CYP2C enzyme, expression in yeast
      cells and characterization of its enzymatic functions.
AB  - We cloned a cDNA encoding a novel CYP2C enzyme, called P450 M-2C, from a marmoset
      liver. The deduced amino acid sequence showed high identities to those of human
      CYP2C8 (87%), CYP2C9 (78%) and CYP2C19 (77%). The P450 M-2C enzyme expressed in
      yeast cells catalyzed p-methylhydroxylation of only tolbutamide among four
      substrates tested, paclitaxel as a CYP2C8 substrate, diclofenac and tolbutamide
      as CYP2C9 substrates and S-mephenytoin as a CYP2C19 substrate. p
      Methylhydroxylation of tolbutamide by marmoset liver microsomes showed monophasic
      kinetics, and the apparent K(m) value (1.2 mM) for the substrate was similar to
      that of the recombinant P450 M-2C (1.8 mM). Although all of the recombinant human
      CYP2C8, CYP2C9 and CYP2C19 expressed in yeast cells catalyzed tolbutamide p
      methylhydroxylation, the kinetic profile of CYP2C8 was most similar to that of
      P450 M-2C. Tolbutamide oxidation by the marmoset liver microsomes and the
      recombinant P450 M-2C was inhibited most effectively by quercetin, a CYP2C8
      inhibitor, followed by omeprazole, a CYP2C19 inhibitor, whereas sulfaphenazole, a
      CYP2C9 inhibitor, was less potent under the conditions used. These results
      indicate that P450 M-2C is the major tolbutamide p-methylhydroxylase in the
      marmoset liver.

PMID- 17010944
TI  - Alpha-band activity reflects reduction of mental effort in a comparison task: a
      source space analysis.
AB  - Comparison processes contribute to many core phenomena of social cognition
      research. Whenever humans judge a given target, they rely on comparisons with a
      pertinent standard. We propose that comparison processes may be so ubiquitous
      because they reduce mental effort. To investigate this possibility, we used dense
      array Electroencephalogram (EEG) recordings together with a minimum norm source
      projection approach. As the dependent variable, we examined changes in parietal
      alpha (8-12 Hz) amplitude during a judgment task. Spectral changes in the alpha
      frequency range have been reliably related to attentional load, cognitive
      arousal, or mental effort. Two groups of participants (n=22) were procedurally
      primed to solve a series of target judgments in a more comparative (experimental
      group) versus more absolute (control group) manner. While the participants
      performed the critical judgment tasks, we recorded changes in alpha amplitude.
      Continuous EEG was transformed into a spherical source space using the minimum
      norm (L2) estimate and spectral changes were subsequently calculated in the
      source domain. Statistical parametric mapping in combination with permutation
      statistics was employed to map regions showing significant group differences.
      Results demonstrate that comparative processing was associated with smaller
      changes in alpha amplitude than absolute processing. This difference was most
      pronounced at parietal source locations, where alpha reduction was at a maximum.
      Temporal analysis suggested that this effect was present particularly during task
      preparation and execution. We conclude that comparative information processing
      may reduce mental effort in judgment tasks.

PMID- 17010943
TI  - Igf-I extends the chondrogenic potential of human articular chondrocytes in
      vitro: molecular association between Sox9 and Erk1/2.
AB  - Expansion of articular chondrocytes in monolayer culture leads to loss of the
      unique chondrocyte phenotype and the cells' redifferentiation capacity.
      Dedifferentiation of chondrocytes in monolayer culture is a challenging problem
      for autologous chondrocyte transplantation (ACT). It is well established that Igf
      I exerts positive anabolic effects on chondrocytes in vivo and in vitro.
      Accordingly, in this study, we examined whether the anabolic insulin-like growth
      factor-I (Igf-I) is capable of extending the chondrogenic potential of
      dedifferentiated chondrocytes in vitro. Chondrocyte monolayers were cultured up
      to 10 passages. At each passage chondrocytes were stimulated with Igf-I (10ng/ml)
      and introduced to high-density cultures for up to 7 days. Expression of collagen
      type II, cartilage-specific proteoglycans, activated caspase-3, integrin beta1,
      extracellular signal-regulated kinase (Erk) and Sox9 was examined by Western
      blotting, immunoprecipitation and immunomorphological techniques. Monolayer
      chondrocytes rapidly lost their differentiated phenotype. When introduced to high
      density cultures, only chondrocytes from P1-P4 redifferentiated. In contrast, Igf
      I treated cells from P1 up to P7 redifferentiated and formed cartilage-like
      tissue in high-density culture. P8-P10 cells exhibited apoptotic alterations and
      produced significantly less matrix. Igf-I markedly increased expression of
      integrin beta1, Erk and Sox9. Immunoprecipitation revealed that phosphorylated
      Erk1/2 physically interacts with Sox9 in chondrocyte nuclei, suggesting a
      previously unreported functional association which was markedly enhanced by Igf
      I. Treatment of chondrocyte cultures with Igf-I stabilizes chondrogenic
      potential, stimulates Sox9 and promotes molecular interactions between Erk and
      Sox9. These effects appear to be regulated by the integrin/MAPK signaling
      pathways.

PMID- 17010945
TI  - Auditory event-related potentials differ in dyslexics even when auditory
      psychophysical performance is normal.
AB  - Developmental dyslexia is characterized by a phonological processing deficit and
      impaired low-level auditory processing may contribute to this problem. However,
      this remains controversial because not all dyslexic individuals show
      psychophysical deficits on auditory processing tasks; hence it has been argued
      that auditory processing deficits are not a causal factor in dyslexia. Because
      behavioral psychophysical tasks include both bottom-up processing and top-down
      strategies, dyslexics' successful coping strategies may positively influence
      their performance on auditory behavioral measures. Therefore we have studied
      whether dyslexics who perform adequately on auditory psychophysical tasks
      nevertheless show electrophysiological evidence of impaired auditory processing.
      We compared auditory event-related mismatch negativity (MMN) potentials to
      frequency modulated (FM) tones at 5, 20 and 240 Hz between dyslexic adults and
      controls. Groups were matched for age, cognitive ability and psychophysical FM
      detection thresholds. The dyslexic group showed significantly smaller MMNs in the
      20 Hz FM condition in both the early (150-300 ms, P=0.010) and late (300-500 ms,
      P=0.049) time frames. A 2-way ANOVA showed a significant group by FM rate
      interaction (P=0.012). There were no significant differences between the groups
      in the 5 Hz or 240 Hz conditions. The magnitude of the 20 Hz FM MMN correlated
      with the degree of discrepancy between cognitive and literacy skills (0.66,
      P=0.003) in the entire group. Thus, even among compensated dyslexics with above
      average cognitive abilities and adequate performance on auditory psychophysical
      tasks, the MMN responses of some dyslexic adults were found to be abnormal.

PMID- 17010946
TI  - Functional degradation of visual cortical cells in aged rats.
AB  - Functional degradation of mammalian visual cortex is associated with aging. It
      has been hypothesized that much of the decline might be mediated by a degradation
      of cortical inhibitory system during senescence. In the present work, we compared
      the properties of adaptation, onset latency and signal-to-noise ratio in primary
      visual cortex of young and old rats using extracellular single-unit techniques.
      The short-term synaptic plasticity of young and old rats was also studied using
      field potential recording techniques. We found significant increased adaptation,
      prolonged onset latency, lower signal-to-noise ratio and decreased short-term
      synaptic plasticity in aged rats. The results are in accordance with previously
      reported functional declines in old monkeys and old cats, indicating a universal
      mechanism of degradation in cortical function that accompanies old age in
      different mammalian species.

PMID- 17010947
TI  - Components of task-set reconfiguration: differential effects of 'switch-to' and
      'switch-away' cues.
AB  - Preparation for a switch in task was manipulated using two types of switch cues:
      'switch-away' from the previous task-set and 'switch-to' a different task-set.
      Increasing cue-stimulus interval resulted in a reduction in reaction time switch
      cost for switch-to trials only. Cue-locked difference waveforms for both switch
      to and switch-away trials showed a large, broad differential positivity, relative
      to repeat waveforms. However, the later part of the differential positivity was
      significantly reduced on switch-away trials. A differential positivity then
      emerged after stimulus onset for switch-away trials only. This suggests that,
      with a long cue-stimulus interval, the new task-set was implemented before
      stimulus onset for switch-to trials, whereas on switch-away trials this process
      was delayed until after stimulus onset leading to increased switch cost. These
      results demonstrate dissociable effects of switching away from the current task
      set and switching to the upcoming task-set and support the interpretation that
      the differential positivity observed for switch-to trials reflects processes
      associated with anticipatory task-set reconfiguration.

PMID- 17010948
TI  - Improved regional cerebral blood flow is important for the protection seen in a
      mouse model of late phase ischemic preconditioning.
AB  - INTRODUCTION: Ischemic preconditioning (IPC) induces protection to cerebral
      ischemia. However, it was previously unclear whether this protection resulted
      from altered susceptibility to ischemia. The current study examines the effects
      of late phase ischemic preconditioning in a mouse model of middle cerebral artery
      occlusion (MCAO). Specific examination of the regional cerebral blood flow (rCBF)
      was conducted. EXPERIMENTAL PROCEDURE: Intra-abdominal radiofrequency probes were
      implanted in animals and core temperature was regulated. Mice were subjected to
      MCAO: (1) brief 15 min duration (preconditioning ischemia) and (2) 45 min MCAO
      (injurious ischemia). Naive (i.e. not preconditioned) animals were compared with
      preconditioned animals (preconditioning ischemia plus injurious ischemia at 72 h
      reperfusion). rCBF was measured using laser Doppler flowmetry (LDF) and magnetic
      resonance cerebral perfusion (MRP) arterial spin labeling. Percentage of brain
      infarcted was compared between groups. RESULTS: rCBF was significantly improved
      in the preconditioned cohorts of mice. Naive animals showed flow reductions to
      16+/-3.59% (MCAO_45; injurious, unpreconditioned) and 17.1+/-8.6% (MCAO_15;
      preconditioning ischemia alone) of baseline, while preconditioned animals had
      flows 33.9+/-13.2% (IPC_45; preconditioned animals with injurious ischemia at 72
      h reperfusion) of baseline (p=0.001). Percentage of brain infarcted was 17.2+/
      6.2% in naive animals, while it was 5.1+/-4.6% in the preconditioned animals
      (p=0.003). MRP of the perfusion to the ischemic hemisphere, in a striatal coronal
      slice of the brain was 26.7+/-5.8% of the contralateral hemisphere in naive
      animals while preconditioned mice had flows of 38.7+/-6.8% of contralateral
      (p=0.04). CONCLUSIONS: Improved rCBF is an important factor in the protection of
      IPC, during injurious MCAO in the mouse. Stringent monitoring of rCBF is required
      in future studies of IPC.

PMID- 17010949
TI  - Characterization of KIAA0513, a novel signaling molecule that interacts with
      modulators of neuroplasticity, apoptosis, and the cytoskeleton.
AB  - KIAA0513 was previously identified as upregulated in the dorsolateral prefrontal
      cortex of subjects with schizophrenia by microarray analysis. In the present
      study, the differential expression in the schizophrenic subjects was confirmed by
      quantitative RT-PCR. The limited homology to proteins of known function and lack
      of functional domains in the encoded protein have made it difficult to predict a
      function for KIAA0513. We used in situ hybridization, RNA blots, western blots,
      and immunocytochemistry to examine KIAA0513 expression in normal brain and
      peripheral tissues. The gene is ubiquitously expressed but is enriched in the
      brain, particularly in the cerebellum. Finally, interacting proteins were
      identified using a yeast two-hybrid screen to functionally characterize the
      protein. KIAA0513 interacts with KIBRA, HAX-1, and INTS4, which also interact
      with proteins involved in neuroplasticity, apoptosis, and cytoskeletal
      regulation. Therefore, KIAA0513 is likely to be involved in signaling pathways
      related to these processes.

PMID- 17010950
TI  - Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial
      activation in the immature brain.
AB  - Inflammation is an important factor for hypoxia-ischemia (HI) brain injury.
      Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to
      injury in the immature brain after HI. To investigate the effects of post-HI
      hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to
      left carotid artery ligation followed by 8% oxygen for 60 min and divided into a
      hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia
      group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR,
      and the protein level was analyzed by Western blot, and the location and source
      of IL-18 were assessed by immunohistochemistry. The significant increase of the
      IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group
      at 24 h and 72 h after HI compared with controls, but the level in the
      ipsilateral hemispheres of the hypothermia group was significantly reduced at
      both time points, compared with the normothermia group, respectively. The IL-18
      protein level in the ipsilateral hemispheres of the normothermia group
      significantly increased at 72 h after HI compared with controls, however, the
      protein level of the hypothermia group was significantly decreased, compared with
      the normothermia group. IL-18-positive cells were observed throughout the entire
      cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of
      normothermia group at 72 h after HI, however, little positive cells were observed
      in the hypothermia group. Double labeling immunostaining found that most of the
      IL-18-positive cells were colocalized with lectin, which is a marker of
      microglia. The number of ameboid microglia (AM) in the normothermia group was
      significantly increased in cortex and CC, compared with the number in controls,
      but there were very few ramified microglia (RM) in these areas. In contrast, the
      number of AM in the hypothermia group was significantly decreased in cortex and
      CC, compared with the number in the normothermia group, and there were no
      significant differences in the number of AM and RM between the hypothermia group
      and controls. In conclusion, we found that IL-18 mRNA and the protein level were
      attenuated by post-HI hypothermia and that post-HI hypothermia may decrease
      microglia activation in the developing brain.

PMID- 17010951
TI  - Central odor processing in subjects experiencing helplessness.
AB  - The aim of the present study was to investigate whether central nervous odor
      processing is affected by the temporary experience of helplessness. To induce
      helplessness, an unsolvable social discrimination test in combination with false
      feedback was used. The EEG was recorded from 60 scalp locations, while two
      standard odors were presented via a constant-flow olfactometer. Helplessness
      attenuated olfactory stimulus processing at an early perceptual stage: the P2 and
      P3-1 amplitudes were reduced in response to both odors. Furthermore, the early
      potentials (N1, P2 and P3-1) of the chemosensory event-related potential (CSERP)
      appeared with longer latencies when subjects received negative feedback. The
      state effects of helplessness resemble the deviations in the CSERP found in
      depressed patients, suggesting a general mood effect.

PMID- 17010952
TI  - Why are women from Venus and men from Mars when they abuse cocaine?
AB  - Both preclinical and clinical studies have shown sexually dimorphic patterns in
      behavioral responses to cocaine in all phases of the cocaine addiction process
      (induction, maintenance, and relapse). Thus, a clear picture is emerging which
      suggests that the biological basis of sex-specific differences in cocaine
      addiction resides in the disparate regulation of the CNS by male and female
      gonadal hormones. This review discusses the role that gonadal hormones play in
      these sexually dimorphic patterns of behavioral responses to cocaine.

PMID- 17010953
TI  - Acute BDNF and cortisol response to low intensity exercise and following ramp
      incremental exercise to exhaustion in humans.
AB  - The effect of short-term aerobic exercise and a following ramp incremental cycle
      ergometry to exhaustion on the acute response of the serum concentrations of
      brain derived neurotrophic factor (BDNF) and cortisol (COR) was examined in 8
      healthy male athletes. Venous and capillary blood samples were drawn at rest,
      immediately after a 10 min warm-up period with aerobic exercise and after a ramp
      test to exhaustion, as well as 3, 6, 10 and 15 min post exercise. Capillary blood
      lactate (LA) concentration and blood gases as well as serum BDNF and COR
      concentrations did not change during the warm-up period. LA was increased
      (p<0.05) at the end of the ramp test and during recovery period while bicarbonate
      concentration, carbon dioxide pressure, pH and base excess were decreased
      (p<0.05) during this period. Serum BDNF was increased at the point of exhaustion
      (p<0.05) while no significant differences were found between values at rest and
      those during recovery period. At 10 and 15 min post incremental exercise, COR
      concentrations were increased (p<0.05) compared to rest. The present study is the
      first to demonstrate in humans that in contrast to short duration aerobic
      exercise immediately after a following short duration high-intensity exercise to
      exhaustion, there is a transient augmentation of serum BDNF concentration. Short
      term response of serum BDNF and COR concentrations differs as BDNF returns to
      baseline level faster than COR.

PMID- 17010954
TI  - Sex- and age-specific effects of anabolic androgenic steroids on reproductive
      behaviors and on GABAergic transmission in neuroendocrine control regions.
AB  - Illicit use of anabolic androgenic steroids (AAS) has become a prevalent health
      concern not only among male professional athletes, but, disturbingly, among a
      growing number of women and adolescent girls. Despite the increasing use of AAS
      among women and adolescents, few studies have focused on the effects of these
      steroids in females, and female adolescent subjects are particularly
      underrepresented. Among the hallmarks of AAS abuse are changes in reproductive
      behaviors. Here, we discuss work from our laboratories on the actions of AAS on
      the onset of puberty and sexual behaviors in female rodents, AAS interactions and
      sex- and age-specific effects of these steroids on neural transmission mediated
      by gamma-aminobutyric acid receptors within forebrain neuroendocrine control
      regions that may underlie AAS-induced changes in these behaviors.

PMID- 17010955
TI  - Effects of static and cyclic loading in regulating extracellular matrix synthesis
      by cardiovascular cells.
AB  - Extracellular matrix (ECM) provides several structural and functional
      characteristics to tissues including cell support, mechanical integrity and
      biological signaling. In cardiovascular tissues, cells produce various ECM
      components such as collagen, elastin, proteoglycans, matrix metalloproteinases,
      growth factors and signaling molecules. The cardiovascular cells (cardiac
      fibroblasts, cardiomyocytes, endothelial cells, and vascular smooth muscle cells)
      sense the changes in mechanical strains applied to them, through cell-surface
      receptors such as integrins and ion channels, and adjust their expression and
      synthesis of ECM molecules in order to adapt their environment to these changes.
      ECM changes due to altered mechanics are evident in numerous pathological
      situations including hypertension, cardiac hypertrophy, myocardial infarction,
      myxomatous heart valve disease, and atherosclerosis. In hypertrophic conditions,
      for example, increased mechanical loading is involved with enhanced collagen
      synthesis, whereas in myxomatous and atherosclerotic conditions reduced
      mechanical strains are accompanied by an accumulation of proteoglycans.
      Therefore, investigating the effects of various strain patterns on cardiovascular
      cells can enhance our understanding of ECM regulation and pathologies. This
      review focuses on the in vitro modulation of the synthesis of various ECM
      molecules through static or cyclic stretching of cardiovascular cells.

PMID- 17010956
TI  - The PPAR regulatory system in cardiac physiology and disease.
AB  - Myocardial energy metabolism is an important determinant of cardiac structure and
      function. Modulating metabolism is therefore an attractive therapeutic avenue for
      the treatment of cardiac disease. The peroxisome proliferator-activated receptor
      family (PPARalpha, beta/delta, gamma) of nuclear receptor transcription factors
      is an important regulator of cardiac metabolism and has been targeted for
      pharmacologic therapies designed to modulate metabolism. The PPARs control
      myocardial metabolism by transcriptionally regulating genes encoding enzymes
      involved in fatty acid and glucose utilization. The expression and activity of
      the PPARs and their coactivator protein PGC-1alpha is dynamically regulated in
      several cardiomyopathic and metabolic diseases. This review will summarize these
      findings and other recent studies regarding the effects of experimental PPAR
      activation and deactivation and its potential impact on cardiomyopathic
      remodeling.

PMID- 17010957
TI  - Innate immunity and inflammation--New frontiers in comparative cardiovascular
      pathology.
AB  - Innate immunity and inflammation play key roles in a wide range of pathology -
      including heart disease and vasculopathies. Current thinking suggests "damage"
      rather than "foreignness" as the actual trigger of the immune system, which has
      caused a dramatic change in how we tend to view the etiopathology of most types
      of heart disease. The future potential of certain anti-inflammatory therapeutic
      strategies in addressing heart disease is intriguing. Still, the Janus face of
      immunity/inflammation cannot be over emphasized as adverse manipulation of these
      systems may prove ineffectual or worse, damaging. Knowledge on functional
      characteristics of individual immune mediators is undoubtedly a central theme,
      but in depth understanding of the multiple biological actions of these molecules,
      as well as their contextual function, is the corner stone in deciding on
      potential future targets for pharmacologic manipulation. Animal models of human
      heart disease are currently being investigated and clinical trials conducted to
      gain further knowledge in this essential area of cardiovascular research, but the
      scarcity of cardiovascular research focusing on signaling molecules and pathways
      of innate immunity is still evident. Genomic and proteomic research in heart
      disease is going through its formative years, and much is still unknown about the
      complex pathway dynamics utilized by the innate immune system. This review will
      provide an overview of the current literature focusing on innate immunity and the
      heart, and hopefully will spark an interest in further basic as well as clinical
      research. As more information on cardiovascular immunity becomes available, this
      will provide a better understanding and thus act as the foundation for potential
      development of new treatment strategies for treatment of cardiovascular
      disorders.

PMID- 17010958
TI  - Ethyl glucuronide and ethyl sulphate determination in serum by liquid
      chromatography-electrospray tandem mass spectrometry.
AB  - BACKGROUND: Ethyl glucuronide (EtG) and ethyl sulphate (EtS) are two ethanol
      metabolites that can be detected in serum up to 8 h after ethanol elimination.
      Their presence is therefore indicative of recent ethanol consumption in case of
      delayed sampling after an event (e.g. car crash). METHODS: A LC-ESI-MS-MS method
      for the determination of EtG and EtS in serum was developed and validated. Two
      product ions together with the parent ions were monitored for identification.
      Pentadeuterated-EtG was used as internal standard. RESULTS: Excellent linearity
      for EtG (from 0.22 to 45 micromol/l) and EtS (from 0.40 to 80 micromol/l) was
      observed (r(2)>or=0.9998). LOD and LLOQ were 0.04 and 0.20 micromol/l for EtG and
      0.08 and 0.40 micromol/l for EtS, respectively. Accuracy (bias) and precision
      (relative standard deviation), studied at four different quality control levels,
      were always better than 7%. Matrix effects were found to be negligible. The
      method was applied to several samples obtained from known alcoholics and social
      drinkers. CONCLUSIONS: A sensitive and specific determination of EtG and EtS in
      serum samples was achieved despite a simple and fast sample preparation. To our
      knowledge, this is the first fully validated method for the simultaneous
      determination of the two alcohol metabolites in serum.

PMID- 17010959
TI  - Analysis of aminoimidazole ribosides by capillary electrophoresis--diagnosing
      defects in second part of purine biosynthetic pathway.
AB  - BACKGROUND: Only three inherited metabolic defects have been identified in purine
      de novo synthesis (PDNS). We present here CE methods for diagnosing defects in
      the second half of PDNS (from sixth to tenth enzymatic conversion) based on
      analysis of aminoimidazole ribosides - dephosphorylated intermediates - in urine.
      METHODS: Assays were performed in an uncoated fused-silica capillary using two
      electrophoretic separation systems: 60 mmol/l borate - 2-amino-2-methyl-1
      propanol-80 mmol/l sodium dodecylsulfate (pH 9.6) and 200 mmol/l phosphate -
      sodium (pH 1.8). RESULTS: The reported conditions allowed separation of all
      metabolites from major urinary constituents with analysis time less than 10 min
      and separation efficiency of 220 and 350 thousands theoretical plates per meter
      for borate and phosphate system, respectively. The intra- and interday
      imprecisions were less than 4.4% and 9.9% CV. Potential usefulness of the methods
      was demonstrated on samples from a patient with adenylosuccinate lyase deficiency
      and Chinese hamster ovary cell lines defective in PDNS. CONCLUSIONS: CE is a
      useful and effective tool in the analysis of aminoimidazole ribosides which
      enables diagnosis of known as well as not so far identified inherited defects of
      PDNS pathway.

PMID- 17010960
TI  - Urinary beta-luteinizing hormone and beta-follicle stimulating hormone
      immunoenzymometric assays for population research.
AB  - OBJECTIVE: We developed assays for measurement of urinary betaLH and betaFSH
      under collection and storage conditions typical of non-clinical research
      settings. DESIGN AND METHODS: IEMAs for free betaLH and total betaFSH were
      validated by standard methods. Stability of urinary betaLH and betaFSH was tested
      across freeze-thaws and stored long term at 4 degrees C or -20 degrees C, or
      short term at room temperature, and with heating to dissociate the subunits.
      RESULTS: The IEMAs exhibited acceptable parallelism, specificity, recovery
      (averaging 100% for betaLH, 97% for betaFSH), imprecision (maximum within-run and
      between run CVs, respectively, 4.8% and 25.7% for betaLH, 5.6% and 17.0% for
      betaFSH), and minimum detectable dose (2.5 pmol/L for betaLH, 6.8 pmol/L for
      betaFSH). Urine and serum measures were highly correlated (r=0.95 for LH, 0.86
      for FSH). There was no consistent decline with any storage type. Dissociation of
      subunits by heating was needed for betaLH, but not betaFSH. CONCLUSION: These
      IEMAs measure free betaLH and total betaFSH, overcoming inter-individual
      variability in, and collection and storage effects on, subunit dissociation,
      without the need for urine preservatives.

PMID- 17010961
TI  - Nonlinear analysis of wheezes using wavelet bicoherence.
AB  - Wheezes, as being abnormal breath sounds, are observed in patients with
      obstructive pulmonary diseases, such as asthma. The aim of this study was to
      capture and analyze the nonlinear characteristics of asthmatic wheezes, reflected
      in the quadrature phase coupling of their harmonics, as they evolve over time
      within the breathing cycle. To achieve this, the continuous wavelet transform
      (CWT) was combined with third-order statistics/spectra. Wheezes from patients
      with diagnosed asthma were drawn from a lung sound database and analyzed in the
      time-bi-frequency domain. The analysis results justified the efficient
      performance of this combinatory approach to reveal and quantify the evolution of
      the nonlinearities of wheezes with time.

PMID- 17010962
TI  - Extraction subject-specific motor imagery time-frequency patterns for single
      trial EEG classification.
AB  - We introduce a new adaptive time-frequency plane feature extraction strategy for
      the segmentation and classification of electroencephalogram (EEG) corresponding
      to left and right hand motor imagery of a brain-computer interface task. The
      proposed algorithm adaptively segments the time axis by dividing the EEG data
      into non-uniform time segments over a dyadic tree. This is followed by grouping
      the expansion coefficients in the frequency axis in each segment. The most
      discriminative features are selected from the segmented time-frequency plane and
      fed to a linear discriminant for classification. The proposed algorithm achieved
      an average classification accuracy of 84.3% on six subjects by selecting the most
      discriminant subspaces for each one. For comparison, classification results based
      on an autoregressive model are also presented where the mean accuracy of the same
      subjects turned out to be 79.5%. Interestingly the subjects and two hemispheres
      of each subject are represented by distinct segmentations and features. This
      indicates that the proposed method can handle inter-subject variability when
      constructing brain-computer interfaces.

PMID- 17010963
TI  - Where people look when watching movies: do all viewers look at the same place?
AB  - Magnification around the most important point of a movie scene (center of
      interest-COI) might aid people with visual impairments that cause resolution
      loss. This will be effective only if most people look at the same place when
      watching a movie. We recorded the eye movements of 20 normally sighted subjects
      as each watched six movie clips, totaling 37.5 min. More than half of the time
      the distribution of subject gaze points fell within an area statistic that was
      less than 12% of the movie scene. Male and older subjects were more likely to
      look in the same place than female and younger subjects, respectively. We
      conclude that the between-subject agreement is sufficient to make the approach
      practical.

PMID- 17010964
TI  - Hematopoietic potential of the pre-fusion allantois.
AB  - We previously showed that the fetal component of the placenta has a vigorous
      hematopoietic activity. Whether this organ is an environmental niche where
      hematopoietic stem cells (HSC) proliferate and become committed to various
      lineages, or whether it is also a site for HSC emergence, was left open. This
      issue can be addressed only if the components that will give rise to the placenta
      are tested prior to vascularization. The fetal part of the placenta forms through
      the fusion of the allantois and the chorionic plate around the stage of 7 somite
      pairs. The allantois, a mesodermal rudiment that provides fetal blood vessels to
      the placenta, was retrieved before fusion. We found in this rudiment expression
      of CD41, a known marker of early embryonic hematopoietic progenitors. c-Kit
      encoding a progenitor specific receptor was also expressed. Significantly, as
      early as the 1-2 somite stage, the allantois yielded erythroid, myeloid and
      multipotent clonogenic progenitors, when pre-cultured in toto prior to seeding in
      a semisolid medium. These results provide evidence that the allantois has
      hematopoietic potential per se. Whether this potential also involves the ability
      to produce HSC is still to be determined.

PMID- 17010965
TI  - Spatially localized Kuzbanian required for specific activation of Notch during
      border cell migration.
AB  - The transmembrane receptor Notch is used repeatedly during development for a
      variety of essential functions. During Drosophila oogenesis, Notch activity is
      required first to specify particular follicle cell fates, then to promote the
      differentiation of all follicle cell types, to promote border cell migration, and
      then to form dorsal appendages, raising the question as to how Notch activity is
      spatially and temporally regulated. Here we show the Notch activity pattern
      during oogenesis. Notch activation was found in many follicle cells at stage 6
      but then at stage 9 was restricted to migrating border cells, despite uniform
      expression of Delta. Expression of Kuzbanian (KUZ), a metalloproteinase that can
      activate Notch as well as cleave other substrates, is enriched in border cells at
      stage 9; and dominant-negative KUZ caused a strong border cell migration defect,
      without affecting expression of markers of border cell fate or follicle cell
      differentiation. Constitutively active Notch rescued the migration defect due to
      dominant-negative KUZ, and conditional alleles of Delta and Notch also exhibited
      border cell migration defects. Expression of two different reporters of Notch
      activity was lost upon expression of dominant-negative KUZ. Taken together these
      results show that Notch activation and KUZ expression are restricted to border
      cells at stage 9 of oogenesis and are required for migration, but not
      differentiation, of these cells. This represents a previously unrecognized
      mechanism for achieving spatial restriction of Notch signaling.

PMID- 17010966
TI  - A role for the hypoblast (AVE) in the initiation of neural induction, independent
      of its ability to position the primitive streak.
AB  - The mouse anterior visceral endoderm (AVE) has been implicated in embryonic
      polarity: it helps to position the primitive streak and some have suggested that
      it might act as a "head organizer", inducing forebrain directly. Here we explore
      the role of the hypoblast (the chick equivalent of the AVE) in the early steps of
      neural induction and patterning. We report that the hypoblast can induce a set of
      very early markers that are later expressed in the nervous system and in the
      forebrain, but only transiently. Different combinations of signals are
      responsible for different aspects of this early transient induction: FGF
      initiates expression of Sox3 and ERNI, retinoic acid can induce Cyp26A1 and only
      a combination of low levels of FGF8 together with Wnt- and BMP-antagonists can
      induce Otx2. BMP- and Wnt-antagonists and retinoic acid, in different
      combinations, can maintain the otherwise transient induction of these markers.
      However, neither the hypoblast nor any of these factors or combinations thereof
      can induce the definitive neural marker Sox2 or the formation of a mature neural
      plate or a forebrain, suggesting that the hypoblast is not a head organizer and
      that other signals remain to be identified. Interestingly, FGF and retinoids,
      generally considered as caudalizing factors, are shown here to play a role in the
      induction of a transient "pre-neural/pre-forebrain" state.

PMID- 17010967
TI  - Pharmacological profile of a novel phosphodiesterase 7A and -4 dual inhibitor, YM
      393059, on acute and chronic inflammation models.
AB  - YM-393059 is a novel phosphodiesterase (PDE) 7A and PDE4 dual inhibitor that
      inhibits both Th1 [interleukin (IL)-2 and interferon-gamma] and Th2 (IL-4)
      cytokines in vitro [Yamamoto, S., Sugahara, S., Naito, R., Ichikawa, A., Ikeda,
      K., Yamada, T., Shimizu, Y., 2006. The effects of a novel phosphodiesterase 7A
      and -4 dual inhibitor, YM-393059, on T-cell-related cytokine production in vitro
      and in vivo. Eur. J. Pharmacol. 541, 106-114]. To characterize the
      pharmacological profile of YM-393059, its effects on several acute and chronic
      inflammation models were examined. In acute inflammation models, YM-393059
      significantly suppressed the delayed-type hypersensitivity reaction to sheep red
      blood cells in mice with an ED(50) value of 17.1 mg/kg. YM-393059 failed to
      suppress paw edema in the carrageenin-induced edema model in rats. These
      pharmacological effects were similar to those of cyclosporine, a typical T-cell
      immunosuppressant. However, YM-393059, but not cyclosporine, significantly
      inhibited zymosan-induced neutrophil accumulation in mice with an ED(50) value of
      25.7 mg/kg. In mouse toluene-2,4-diisocyanate-induced contact dermatitis, a
      chronic inflammation model, YM-393059 and cyclosporine significantly suppressed
      ear edema at doses of 30 and 20 mg/kg, respectively. In this model, YM-393059
      also tended to reduce the serum immunoglobulin E antibody level, whereas
      cyclosporine dramatically potentiated it. These results suggest that YM-393059
      inhibits both Th1- and Th2-cell-dependent reactions and also the function of
      neutrophils.

PMID- 17010968
TI  - The shedding activity of ADAM17 is sequestered in lipid rafts.
AB  - The tumor necrosis factor-alpha (TNF) converting enzyme (ADAM17) is a
      metalloprotease-disintegrin responsible for the cleavage of several biologically
      active transmembrane proteins. However, the substrate specificity of ADAM17 and
      the regulation of its shedding activity are still poorly understood. Here, we
      report that during its transport through the Golgi apparatus, ADAM17 is included
      in cholesterol-rich membrane microdomains (lipid rafts) where its prodomain is
      cleaved by furin. Consequently, ADAM17 shedding activity is sequestered in lipid
      rafts, which is confirmed by the fact that metalloproteinase inhibition increases
      the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in
      lipid rafts. Membrane cholesterol depletion increases the ADAM17-dependent
      shedding of these substrates demonstrating the importance of lipid rafts in the
      control of this process. Furthermore, ADAM17 substrates are present in different
      proportions in lipid rafts, suggesting that the entry of each of these substrates
      in these particular membrane microdomains is specifically regulated. Our data
      support the idea that one of the mechanisms regulating ADAM17 substrate cleavage
      involves protein partitioning in lipid rafts.

PMID- 17010969
TI  - Mutations that affect meiosis in male mice influence the dynamics of the mid
      preleptotene and bouquet stages.
AB  - Meiosis pairs and segregates homologous chromosomes and thereby forms haploid
      germ cells to compensate the genome doubling at fertilization. Homologue pairing
      in many eukaryotic species depends on formation of DNA double strand breaks
      (DSBs) during early prophase I when telomeres begin to cluster at the nuclear
      periphery (bouquet stage). By fluorescence in situ hybridization criteria, we
      observe that mid-preleptotene and bouquet stage frequencies are altered in male
      mice deficient for proteins required for recombination, ubiquitin conjugation and
      telomere length control. The generally low frequencies of mid-preleptotene
      spermatocytes were significantly increased in male mice lacking recombination
      proteins SPO11, MEI1, MLH1, KU80, ubiquitin conjugating enzyme HR6B, and in mice
      with only one copy of the telomere length regulator Terf1. The bouquet stage was
      significantly enriched in Atm(-/-), Spo11(-/-), Mei1(m1Jcs/m1Jcs), Mlh1(-/-),
      Terf1(+/-) and Hr6b(-/-) spermatogenesis, but not in mice lacking recombination
      proteins DMC1 and HOP2, the non-homologous end-joining DNA repair factor KU80 and
      the ATM downstream effector GADD45a. Mice defective in spermiogenesis (Tnp1(-/-),
      Gmcl1(-/-), Asm(-/-)) showed wild-type mid-preleptotene and bouquet frequencies.
      A low frequency of bouquet spermatocytes in Spo11(-/-)Atm(-/-) spermatogenesis
      suggests that DSBs contribute to the Atm(-/-)-correlated bouquet stage exit
      defect. Insignificant changes of bouquet frequencies in mice with defects in
      early stages of DSB repair (Dmc1(-/-), Hop2(-/-)) suggest that there is an ATM
      specific influence on bouquet stage duration. Altogether, it appears that several
      pathways influence telomere dynamics in mammalian meiosis.

PMID- 17010970
TI  - Dysfunctional channels are making noise in CAG triplet repeat disorders.

PMID- 17010971
TI  - Developmental potential of radial glia investigated by transplantation into the
      developing rat ventricular system in utero.
AB  - During development there is a clear correlation between position of dividing
      progenitor cells, mode of division and developmental potential, suggesting that
      the local environment of progenitor cells may influence their cell fate [ 17 (6),
      639-647]. The contribution of these conditions was investigated here by
      transplantation of radial glial progenitor cells into isotopic, isochronic,
      heterotopic and heterochronic environment conditions. Neuronal cells were removed
      from E14 spinal cords using negative immunoselection. The remaining radial glia
      were transplanted into the ventricular system of host embryos and pups. Distance
      of migration as well as morphological and antigenic phenotype of transplanted
      radial glia was examined after various survival times post transplantation. Host
      age clearly influenced migration and differentiation of transplant cells, with
      transplant cells migrating further in younger hosts and differentiating earlier
      in older aged host environments. Evidence is presented showing that most
      transplanted spinal cord radial glia give rise to astrocytes. In addition some
      transplanted radial glia were shown to give rise to neurons in spinal cord
      regions. Radial glia did not appear to generate neurons in the brains of host
      animals until postnatal ages, perhaps because transplanted radial glia were
      isolated from spinal cord and thus may not have been influenced to behave as
      endogenous radial glia in the brain which commonly produce neurons.

PMID- 17010972
TI  - Mitochondria mass is low in mouse substantia nigra dopamine neurons: implications
      for Parkinson's disease.
AB  - In Parkinson's disease (PD) there is a selective loss of certain midbrain
      dopaminergic (DA) neurons. The most vulnerable neurons reside in the substantia
      nigra zona compacta (SNC), whereas the DA neurons in the ventral tegmental area
      (VTA) and interfascicular (IF) nucleus are less vulnerable to degeneration. Many
      sporadic PD patients have a defect in mitochondria respiration, and some of the
      genes that cause PD are mitochondrial-related (e.g., PINK1, Parkin, DJ1). The
      present study sought to determine whether mitochondria mass is different in SNC
      neurons compared to other midbrain DA neurons and to non-DA neurons in the mouse.
      At the electron microscopic level, mitochondria in the SN DA neurons occupy 40%
      less of the soma and dendritic area than in the SN non-DA neurons. The area
      occupied by mitochondria in the SN DA neurons is also lower than in the VTA
      neurons, although not different from the IF neurons. The red nucleus somata have
      the largest percentage of the somata occupied by mitochondria (12%). Mitochondria
      size is related to somata size; the largest mitochondria are found in the red
      nucleus neurons and the smallest mitochondria are found in the IF neurons. At the
      light microscopic level, SNC, VTA and IF DA neurons have <50% of the cytoplasm
      immunostained with the mitochondrial antibody 1D6, whereas non-DA neurons in the
      same midbrain regions contain mitochondria areas up to >65% of the cytoplasm
      area. These data indicate that mitochondria size and mass are not the same for
      all neurons, and the SNC DA neurons have relatively low mitochondria mass. The
      low mitochondria mass in SNC DA neurons may contribute to the selective
      vulnerability of these neurons in certain rodent models of PD.

PMID- 17010973
TI  - Changes in rat brainstem responsiveness to somatovisceral inputs following acute
      bladder irritation.
AB  - A number of clinical studies indicate the coexistence of multiple chronic pelvic
      diseases and pain syndromes. An association between various conditions related to
      the pelvic viscera may relate to a high degree of central visceral convergence,
      which is a requisite for the cross-organ coordination that is necessary for their
      normal functions. In the present study, a population of neurons receiving a high
      degree of somatovisceral convergence (those in the medullary reticular formation-
      MRF) was targeted in order to examine the effect of infusing a chemical irritant
      into one organ on the responsiveness of convergent inputs from various visceral
      and somatic regions of the body, using electrophysiological techniques. Acute
      irritation of the urinary bladder (UB) with 2% acetic acid significantly
      decreased the percentage of convergent MRF neuronal responses to UB distention
      and urethral infusion and significantly increased the percentage responding to
      whole body, mainly due to stimulation of the face. Irritation also produced a
      significant increase in the response duration of MRF neurons to distention of
      colon as well as the bladder (for those few UB responses that still remained).
      These results indicate that a pelvic/visceral pathology confined to one organ can
      affect at least some of the convergent responses from other regions of the body.
      The findings suggest that MRF neurons contribute to the cross-talk between
      different regions of the body under both normal and pathological conditions.

PMID- 17010974
TI  - Effects of affiliation arousal (hope of closeness) and affiliation stress (fear
      of rejection) on progesterone and cortisol.
AB  - Our prior research has suggested a connection between progesterone (PROG) and
      implicit affiliation motivation, the non-conscious drive for positive social
      contact. In particular, experimental arousal of affiliation motivation led to
      relative PROG increase in women and men [Schultheiss, O.C., Wirth, M.M., Stanton,
      S.J., 2004. Effects of affiliation and power motivation arousal on salivary
      progesterone and testosterone. Horm. Behav. 46(5), 592-599]. The present study
      aimed to (1) replicate this effect, (2) simultaneously assess cortisol (CORT)
      levels in this paradigm in order to rule out non-specific adrenal effects induced
      by affiliation arousal, and (3) examine effects on PROG and CORT of approach
      (hope for closeness, HOC) versus avoidance (fear of rejection, FOR) affiliation
      arousal. These motivational states were experimentally aroused in participants
      using film segments containing approach- or avoidance-oriented affiliation
      related themes; a neutral film segment was used as a control condition. The film
      segments affected participants' implicit affiliation motivation and self-reported
      mood, demonstrating effectiveness of the manipulation. In the FOR condition,
      participants' CORT and PROG were increased post-film, consistent with the idea
      that fear of rejection is stressful. We did not replicate our prior finding of
      PROG increase following the HOC manipulation. However, relationships between PROG
      and implicit affiliation motivation were apparent across conditions. In
      particular, PROG co-varied positively with affiliation motivation, and baseline
      affiliation motivation positively predicted PROG increase in the FOR condition.
      As prior research implicates PROG in down-regulation of stress, we speculate that
      PROG release during stress may encourage affiliation for stress reduction
      purposes.

PMID- 17010975
TI  - Contemporary medical therapy for polycystic ovary syndrome.
AB  - Polycystic ovary syndrome is a multi-system endocrinopathy with long-term
      metabolic and cardiovascular health consequences. Patients typically present due
      to symptoms of irregular menstruation, hair growth, or infertility; however,
      recent management options are aimed at further treating underlying glucose
      insulin abnormalities as well as androgen excess for proactive control of
      symptoms. By a 2003 international consensus conference, diagnosis is made by two
      out of three criteria: chronic oligoovulation or anovulation after excluding
      secondary causes, clinical or biochemical evidence of hyperandrogenism (but not
      necessarily hirsutism due to inter-patient variability in hair follicle
      sensitivity), and radiological evidence of polycystic ovaries. Traditional
      medical treatment options include oral contraceptive pills, cyclic progestins,
      ovulation induction, and anti-androgenic medications (aldosterone antagonist,
      5alpha-reductase antagonist, and follicle ornithine decarboxylase inhibitor).
      Recent pharmacotherapies include insulin-sensitizing medications metformin and
      two thiazolidinediones (rosiglitazone/Avandia and pioglitazone/Actos), a CYP19
      aromatase inhibitor (letrozole/Femara), and statins to potentially lower
      testosterone levels.

PMID- 17010976
TI  - Support in nursing--an evolutionary concept analysis.
AB  - BACKGROUND: This research into the concept of support was undertaken because of
      the recurrent use of the concept in nursing research and especially because of
      the vital importance of support to family carers of older persons. AIM: To
      inductively develop a definition of support, specifically in the context of
      family care of frail aged persons. METHOD: The study followed the evolutionary
      method of concept analysis. The study was based on data from scientific
      publications, encyclopaedias and dictionaries. In order to secure a
      representative sample, highly systematic means of sampling were used. RESULTS:
      Working with the data underpinning this study, it was possible to put forward a
      definition of support for family carers who care for a frail aged person at home.
      The two major dimensions, as described under attributes, were merged into the
      following definition: "Support entails the provision of general tangibles such as
      information, education, economic aid, goods and external services. They are
      prerequisites for facilitating the family carers' competence or capacity in care.
      Moreover it entails necessary qualities such as individualization, adaptability,
      lastingness, room for verbalizing emotions as well as an idea of reciprocal
      symmetrical exchange between involved parties.

PMID- 17010977
TI  - Quantification of the slug parasitic nematode Phasmarhabditis hermaphrodita from
      soil samples using real time qPCR.
AB  - Phasmarhabditis hermaphrodita is a nematode parasite that infects and kills
      several species of slugs. The nematode is produced commercially as a biological
      control agent for slug pests of agriculture and horticulture. Given the
      difficulties of distinguishing this species from other nematode species in soil
      samples, very little is known about its natural ecology or its behaviour and
      persistence following application for biological control. Here we describe a
      method to quantify P. hermaphrodita in soil samples based on real time PCR. We
      designed primers and a dual labelled fluorescent probe that can be used to
      quantify numbers of P. hermaphrodita and which is capable of distinguishing this
      species from the morphologically identical Phasmarhabditis neopapillosa. We
      compared different methods whereby the entire nematode community is extracted
      prior to DNA extraction, and three methods to extract DNA directly from soil
      samples. Both nematode extraction and DNA extraction from large (10 g) samples of
      soil gave reliable estimates of nematode numbers, but methods which extracted DNA
      from small (1g or less) soil samples substantially underestimated numbers.
      However, direct extraction of DNA from soils may overestimate numbers of live
      nematodes as DNA from dead nematodes was found to persist in soil for at least 6
      days. The technique could be modified for detection and quantification of all
      soil borne parasitic nematodes.

PMID- 17010978
TI  - Association of high alpha2-Heremans-Schmid glycoprotein/fetuin concentration in
      serum and intima-media thickness in patients with atherosclerotic vascular
      disease and low bone mass.
AB  - OBJECTIVE: Alpha2-Heremans-Schmid glycoprotein (AHSG; fetuin), a member of the
      cystatin superfamily of cysteine protease inhibitors involved in vascular
      pathology and bone metabolism, has been reported to be reduced in patients with
      atherosclerosis and medial calcification related to end stage renal disease or
      dialysis. No data on fetuin in patients with peripheral artery disease associated
      with low bone mass and normal renal function are available in the literature. In
      the present study we evaluated serum fetuin concentrations, bone mass, and
      markers of bone turnover in patients with atherosclerosis of peripheral vessels
      and normal kidney function. PATIENTS AND METHODS: Ninety consecutive patients
      with evidence of atherosclerotic plaques at the common carotid or femoral artery
      were studied. Severity grade of disease was documented by ultrasound measurement
      of intima-media thickness (IMT). Fasting serum levels of fetuin were measured by
      sandwich enzyme immunoassay. MAIN RESULTS: The mean patient serum concentration
      of fetuin was 57.68+/-13.6 ng/ml, significantly higher than that of control
      subjects (41.6+/-7.6 ng/ml; p<0.001). The mean serum concentration of bone
      specific alkaline phosphatase (BAP) were 8.4+/-2.3 microg/l, significantly lower
      than controls (13.6+/-1.6 microg/l; p<0.001). Fetuin was correlated with IMT
      (r=0.8530; p<0.0001) and inversely correlated with BAP (r=-0.5503; p<0.0001).
      Patients had a vertebral and femoral bone mass significantly lower than controls.
      CONCLUSION: This study documented for the first time that, in patients with
      atherosclerosis of peripheral vessels, serum fetuin levels were higher than in
      healthy subjects, and correlated with the severity of disease; further studies
      are required to analyse the role of AHSG as an independent predictor of
      atherosclerotic disease and low bone mass in patients with normal renal function.

PMID- 17010979
TI  - The effects of chronic tea intake on platelet activation and inflammation: a
      double-blind placebo controlled trial.
AB  - BACKGROUND: Tea drinking appears to protect against the development of coronary
      heart disease (CHD), but the mediating pathways are uncertain. We studied the
      effects of 6 weeks of black tea or placebo on platelet activation, C-reactive
      protein (CRP), total antioxidant status, and soluble (s) P-Selectin in a
      randomized double-blind trial. METHODS: Healthy non-smoking men aged 18-55 years
      were randomized to black tea (N=37) or placebo (N=38) following a 4-week washout
      period during which they drank no tea, coffee or caffeinated beverages, but
      consumed caffeinated placebo tea. Bloods were drawn after 6 weeks of treatment.
      Platelet activation was assessed by measuring leukocyte-platelet aggregates using
      whole blood flow cytometry. RESULTS: Following treatment, the tea group had fewer
      monocyte-platelet aggregates (means 5.84 versus 6.60%, P=0.027), neutrophil
      platelet aggregates (P=0.017), total leukocyte-platelet aggregates (P=0.027), and
      lower plasma C-reactive protein (means 0.76 versus 0.97 mg/L, P=0.05) than the
      placebo group. There were no differences in total antioxidant status or soluble P
      Selectin. CONCLUSIONS: Chronic tea consumption reduces platelet activation and
      plasma C-reactive protein in healthy men. Effects cannot be attributed to
      observer bias or lifestyle confounders. These effects of tea may contribute to
      sustained cardiovascular health.

PMID- 17010980
TI  - Study of substrate inhibition by electrophoretically mediated microanalysis in
      partially filled capillary.
AB  - Substrate inhibition is a common phenomenon in enzyme kinetics. We report here
      for the first time its study by a combination of the electrophoretically mediated
      microanalysis (EMMA) methodology with a partial filling technique. In this setup,
      the part of capillary is filled with the buffer best for the enzymatic reaction
      whereas, the rest of the capillary is filled with the background electrolyte
      optimal for separation of substrates and products. In the case of haloalkane
      dehalogenase, a model enzyme selected for this study, the enzymatic reaction was
      performed in 20 mM glycine buffer (pH 8.6) whereas 20 mM beta-alanine
      hydrochloric acid buffer (pH 3.5) was used as a background electrolyte in
      combination with direct detection at 200 nm. The whole study was performed on
      poorly soluble brominated substrate--1,2-dibromoethane. As a result it was first
      necessary to find the compromise between the concentrations of the enzyme and the
      substrate preserving both the adequate sensitivity of the assay and at the same
      time the attainable substrate solubility. By means of the developed EMMA
      methodology we were able to determine the Michaelis constant (K(M)) as well as
      the substrate inhibition constant (K(SI)). The value of K(M) and K(SI) obtained
      were 7.7+/-2.5 mM and 1.1+/-0.4 mM, respectively. Observation of the substrate
      inhibition of haloalkane dehalogenase by 1,2-dibromoethane is in accordance with
      previous literature data.

PMID- 17010981
TI  - Dynamic hollow fiber protected liquid phase microextraction and quantification
      using gas chromatography combined with electron capture detection of
      organochlorine pesticides in green tea leaves and ready-to-drink tea.
AB  - The dynamic hollow fiber protected liquid phase microextraction (DHFP-LPME)
      technique was evaluated for the extraction of organochlorine pesticides (OCPs) in
      green tea leaves and ready-to-drink tea prior to gas chromatography combined
      electron capture detection (GC-ECD) analysis. A conventional microsyringe with a
      1.5 cm length of hollow fiber attached to its needle was connected to a syringe
      pump to perform the extraction. The microsyringe was used as both the
      microextraction device and the sample introduction device for GC-ECD analysis. In
      this work, the organochlorine pesticides were extracted and condensed to a volume
      of 3 microl of organic extracting solvent (1-octanol) confined within a 1.5 cm
      length of hollow fiber. The effects of extraction solvent, extraction time,
      sample agitation, plunger speed, and extraction temperature and salt
      concentration content on the extraction performance were also investigated. Good
      enrichments were achieved (34-297-fold) with this method, and good
      repeatabilities of extraction were obtained, with full name (RSDs) below 12.57%.
      Detection limits were much below 1 microg l(-1) for ready-to-drink tea and much
      below 1 microg g(-1) for green tea leaves.

PMID- 17010982
TI  - Polymer-mediated extraction of the fluorescent compounds derived by Hantzsch
      reaction with dimedone for the sensitive determination of aliphatic aldehydes in
      air.
AB  - An extraction method based on the thermo-responsive precipitation of a water
      soluble polymer, poly(N-isopropylacrylamide) [PNIPAAm], was applied to the
      concentration of dimedone (5,5-dimethylcycrohexane-1,3-dion) derivatives for the
      highly sensitive determination of aldehydes in air. Aliphatic aldehydes including
      formaldehyde, acetaldehyde, propanal, 1-butanal, 1-heptanal, and 1-hexanal in air
      were well solubilized into the aqueous solution of dimedone and ammonium acetate
      by mixing the solution and air sample in a polyvinyl fluoride bag. Fluorescent
      derivatives of aldehydes that had formed by the Hantzsch reaction with dimedone
      were concentrated by polymer-mediated extraction. The recoveries of the
      fluorescent compounds increased with increasing the carbon number of aldehyde and
      were more than 80% for the derivatives from aldehydes having more than three
      carbon atoms under the optimal conditions. Microgram per m3 (sub-ppb) levels of
      the aliphatic aldehydes, propanal, 1-butanal, 1-heptanal, and 1-hexanal, in
      ambient air were successfully determined by HPLC separation with fluorometric
      detection. The sampling volume and time required were only 1l and 20 s,
      respectively.

PMID- 17010983
TI  - Comparison of ceramic hydroxy- and fluoroapatite versus Protein A/G-based resins
      in the isolation of a recombinant human antibody from cell culture supernatant.
AB  - A recombinant human antibody (IgG(1)-subtype) was produced in Chinese Hamster
      Ovary (CHO) cells. Alternatives to the established isolation by Protein A
      affinity chromatography were investigated. Neither an alternative elution agent
      (Arginine) nor an alternative affinity ligand (Protein G) resulted in an
      improvement in yield and/or purity. Subsequently, apatite stationary phases
      including a novel ceramic fluoroapatite material were tested. By applying a
      double gradient (first 0 to 1M NaCl, then 0.01 to 0.4M phosphate) the culture
      supernatant was separated into three fractions: the flow through, which contained
      no active antibody, the NaCl-eluate, which contained the antibody and no other
      discernible protein contaminants, and a fraction that eluted in the phosphate
      gradient and contained several proteins, but no active antibody. In case of the
      hydroxyapatite, retention of the antibody decreased and yield increased when the
      pH was raised from 6.0 to 8.2 (isoelectric point (pI) of the antibody: 8.3), to
      reach a yield of 71% at pH of 8.2. In case of the fluoroapatite, retention was
      also found to increase with increasing mobile phase pH, but the yields went
      through a maximum (of ca. 90%) at a mobile phase pH of 7.0. No traces of
      contaminants were seen in the corresponding gel. This is the first time that
      yields of 90% and such high purities have been reported as the result of a single
      chromatographic step for the antibody in question with either (Protein A)
      affinity or apatite chromatography.

PMID- 17010984
TI  - Direct synthesis and bonding origins of monolayer-protected silver nanocrystals
      from silver nitrate through in situ ligand exchange.
AB  - In this study, we attempt to present a direct synthesis of narrowly dispersed
      silver nanoparticles in a highly concentrated organic phase (>2 M) without the
      use of a size-selection process. The fully organic phase system contains silver
      nitrate as a silver precursor, n-butylamine as a medium dissolving the silver
      salt, dodecanoic acid as a capping molecule, toluene as a medium, and NaBH4 as a
      reducing reagent. Even using only generic chemicals, monodisperse silver
      nanocrystals with a size of 7 nm were easily synthesized on the 100-g scale in a
      1-L reactor. In addition, systematic studies revealed that the silver
      nanocrystals synthesized through in situ ligand exchange were stabilized through
      bidentate bridging of carboxyl groups in dodecanoic acid.

PMID- 17010985
TI  - Control of the electrical conductivity of composites of antimony doped tin oxide
      (ATO) nanoparticles and acrylate by grafting of 3
      methacryloxypropyltrimethoxysilane (MPS).
AB  - The effect of the addition of antimony doped tin oxide (ATO) nanoparticles on the
      electrical conductivity of acrylate films is described. To enable dispersing of
      ATO in acrylate matrices, 3-methacryloxypropyltrimethoxysilane (MPS) was grafted
      on the surface of the filler. The amount of MPS used for this surface
      modification was found to strongly affect the electrical conductivity. Surface
      modification with a large amount of MPS resulted in colloidally stable
      dispersions of ATO, leading to a homogeneous distribution. Surface modification
      with small amounts of MPS led to instable ATO dispersions and aggregation of ATO
      into a fractal type network, which gives a much higher conductivity especially at
      low-volume fractions. For composites with a fractal type ATO network a second
      effect was found. Decreasing the amount of on ATO grafted MPS resulted in an
      increase of the electrical conduction between the ATO particles.

PMID- 17010986
TI  - Diffuse reflectance infrared Fourier transform spectroscopy as a tool to
      characterise water in adsorption/confinement situations.
AB  - We present experimental data acquired by diffuse reflectance infrared
      spectroscopy in the mid-IR (4000-400 cm(-1)), on micrometric-sized mineral grain
      powders. The spectral evolution of the OH-stretching band is followed when the
      adsorbed water film is thinned under dry conditions, from high to low hydration
      states. The IR bands are found to be characteristic of the degree of
      adsorption/confinement of the liquid water. The OH-stretching band is shifted
      toward shorter wavenumbers than in bulk water, showing that a significant portion
      of adsorbed water has a higher intermolecular bonding energy. Complementary
      treatment of the kinetics of water desorption, varying with the surface forces in
      the water film, confirms the relationships of these bands with the constrained
      water state. We distinguish different water types obeying liquid-liquid
      interactions (free and capillary water) or dominated by solid-water interactions
      (confined and adsorbed water). Part of this study is devoted to mesoporous silica
      MCM-41, of interest due to the restricted geometries of its mesopores (4.7 nm)
      favouring the confined water state. The methodology allows us to distinguish bulk
      and adsorbed/confined water, using spectral analysis coupled with an
      understanding of the dynamic behaviour of the desorption process.

PMID- 17010987
TI  - Investigating sorption-driven dissolved organic matter fractionation by
      multidimensional fluorescence spectroscopy and PARAFAC.
AB  - Soil organic matter is involved in many ecosystem processes, such as nutrient
      supply, metal solubilization, and carbon sequestration. This study examined the
      ability of multidimensional fluorescence spectroscopy and parallel factor
      analysis (PARAFAC) to provide detailed chemical information on the preferential
      sorption of higher-molecular-weight components of natural organic matter onto
      mineral surfaces. Dissolved organic matter (DOM) from soil organic horizons and
      tree leaf tissues was obtained using water extracts. The suite of fluorescence
      spectra was modeled with PARAFAC and it was revealed that the DOM extracts
      contained five fluorescing components: tryptophan-like (peak location at
      excitation <255 nm:emission 342 nm), tyrosine-like (276 nm:312 nm), and three
      humic-substance-like components (<255 nm:456 nm, 309 nm:426 nm, <255 nm:401 nm).
      In general, adsorption onto goethite and gibbsite increased with increasing DOM
      molecular weight and humification. PARAFAC analysis of the pre- and post-sorption
      DOM indicated that the ordering of sorption extent was humic-like components
      (average 91% sorption) > tryptophan-like components (52% sorption) > tyrosine
      like components (29% sorption). This differential sorption of the modeled DOM
      components in both the soil organic horizon and leaf tissue extracts led to the
      fractionation of DOM. The results of this study demonstrate that multidimensional
      fluorescence spectroscopy combined with PARAFAC can quantitatively describe the
      chemical fractionation process due to the interaction of DOM with mineral
      surfaces.

PMID- 17010988
TI  - Working memory, reading, and mathematical skills in children with developmental
      coordination disorder.
AB  - The aim of the present study was investigate the relationship between working
      memory and reading and mathematical skills in 55 children diagnosed with
      developmental coordination disorder (DCD). The findings indicate a pervasive
      memory deficit in all memory measures. In particular, deficits observed in
      visuospatial short-term and working memory tasks were significantly worse than in
      the verbal short-term memory ones. On the basis of these deficits, the sample was
      divided into high and low visuospatial memory ability groups. The low
      visuospatial memory group performed significantly worse on the attainment
      measures compared to the high visuospatial memory group, even when the
      contribution of IQ was taken into account. When the sample was divided into high
      and low verbal working memory ability groups, verbal working memory skills made a
      unique contribution to attainment only when verbal IQ was taken into account, but
      not when performance IQ was statistically controlled. It is possible that the
      processing demands of the working memory tasks together with the active motor
      component reflected in the visuospatial memory tasks and performance IQ subtest
      both play a crucial role in learning in children with DCD.

PMID- 17010989
TI  - PKC-betaII sensitizes cardiac myofilaments to Ca2+ by phosphorylating troponin I
      on threonine-144.
AB  - Ventricular myocytes express Galphaq-coupled receptors that can mediate enhanced
      contractility by increasing the sensitivity of the contractile apparatus to
      Ca(2+). The precise mechanisms underlying this change have been difficult to
      define, in part because myofilament regulatory proteins contain multiple
      phosphorylation sites for protein kinase C (PKC), protein kinase A (PKA) and
      myosin light chain kinase (MLCK), with potentially opposing effects. MLCK
      increases whereas PKC and PKA have a strong tendency to decrease myofilament
      Ca(2+) sensitivity in myocardium. Here we show in mouse cardiac myocytes that PKC
      betaII can increase Ca(2+) sensitivity of tension by a similar magnitude to MLCK
      but via a distinct mechanism. For PKC-betaII (32)P-incorporation occurred
      primarily into cardiac troponin I (cTnI) and functional effects were highly
      dependent upon mutations in phosphorylation sites of cTnI. Replacement of serines
      23/24 (PKA sites) with alanine prevented cross-phosphorylation of these sites,
      reduced (32)P-incorporation into cTnI by half and resulted in myofilament Ca(2+)
      sensitization rather than desensitization in response to PKC-betaII. Replacement
      of three additional sites on cTnI, serines-43/45 and threonine-144, eliminated
      PKC-betaII-mediated Ca(2+) sensitization and the remaining (32)P-incorporation
      into cTnI. A preference for PKC-betaII phosphorylation of threonine-144 in the
      intact filament lattice was revealed by differential stable isotope labeling and
      supported by an analysis of peptide phosphorylation. The results suggest that
      threonine-144 within the critical inhibitory domain of cTnI represents a novel
      site of regulation of myofilament Ca(2+) sensitivity by PKC-betaII, with possible
      implications for chronically stressed or diseased hearts.

PMID- 17010990
TI  - Structural basis for subunit assembly in UDP-glucose pyrophosphorylase from
      Saccharomyces cerevisiae.
AB  - UDP-glucose is the universal activated form of glucose, employed in all organisms
      for glucosyl transfer reactions and as precursor for various activated
      carbohydrates. In animal and fungal metabolism, UDP-glucose is required for
      utilization of galactose and for the synthesis of glycogen, the major
      carbohydrate storage polymer. The formation of UDP-glucose is catalyzed by UDP
      glucose pyrophosphorylase (UGPase), which is highly conserved among eukaryotes.
      Here, we present the crystal structure of yeast UGPase, Ugp1p. Both in solution
      and in the crystal, Ugp1p forms homooctamers, which represent the enzymatically
      active form of the protein. Ugp1p subunits consist of three domains, with the
      active site presumably located in the central SpsA GnT I core (SGC) domain. The
      association in the octamer is mediated by contacts between left-handed beta
      helices in the C-terminal domains, forming a toroidal solenoid structure in the
      core of the complex. The catalytic domains attached to this scaffold core do not
      directly contact each other, consistent with simple Michaelis-Menten kinetics
      found for Ugp1p. Conservation of hydrophobic residues at the subunit interfaces
      suggests that all fungal and animal homologs form this quarternary structure
      arrangement in contrast to monomeric plant UGPases, which have charged residues
      at these positions. Implications of this oligomeric arrangement for regulation of
      UGPase activity in fungi and animals are discussed.

PMID- 17010991
TI  - The crystal structure of the bacteriophage PSA endolysin reveals a unique fold
      responsible for specific recognition of Listeria cell walls.
AB  - Bacteriophage murein hydrolases exhibit high specificity towards the cell walls
      of their host bacteria. This specificity is mostly provided by a structurally
      well defined cell wall-binding domain that attaches the enzyme to its solid
      substrate. To gain deeper insight into this mechanism we have crystallized the
      complete 314 amino acid endolysin from the temperate Listeria monocytogenes phage
      PSA. The crystal structure of PlyPSA was determined by single wavelength
      anomalous dispersion methods and refined to 1.8 A resolution. The two functional
      domains of the polypeptide, providing cell wall-binding and enzymatic activities,
      can be clearly distinguished and are connected via a linker segment of six amino
      acid residues. The core of the N-acetylmuramoyl-L-alanine amidase moiety is
      formed by a twisted, six-stranded beta-sheet flanked by six helices. Although the
      catalytic domain is unique among the known Listeria phage endolysins, its
      structure is highly similar to known phosphorylase/hydrolase-like alpha/beta
      proteins, including an autolysin amidase from Paenibacillus polymyxa. In
      contrast, the C-terminal domain of PlyPSA features a novel fold, comprising two
      copies of a beta-barrel-like motif, which are held together by means of swapped
      beta-strands. The architecture of the enzyme with its two separate domains
      explains its unique substrate recognition properties and also provides insight
      into the lytic mechanisms of related Listeria phage endolysins, a class of
      enzymes that bear biotechnological potential.

PMID- 17010992
TI  - Heat shock protein 70 inhibits alpha-synuclein fibril formation via interactions
      with diverse intermediates.
AB  - alpha-Synuclein (AS) is a main component of Lewy bodies in midbrain dopamine
      neurons pathologically characteristic of Parkinson's disease. We show that heat
      shock protein (Hsp) 70 inhibits AS fibril formation via preventing the formation
      of prefibrillar AS (PreAS), binding with PreAS to impede nuclei formation, and
      binding with nuclei to retard fibril elongation. Also, Hsp70 suppresses the PreAS
      induced permeabilization of vesicular membrane through interactions with PreAS.
      The substrate-binding domain alone is sufficient for Hsp70 to inhibit AS fibril
      formation. The binding of Hsp70 with PreAS only requires the substrate-binding
      subdomain, and the binding with AS nuclei requires the C-terminal lid subdomain
      as well. The results may form the molecular basis for elucidating the mechanism
      of AS fibril formation and the crucial roles of chaperones in protecting proteins
      from toxic conversion in many conformational diseases.

PMID- 17010993
TI  - Anticipation of aversive stimuli activates extended amygdala in unipolar
      depression.
AB  - According to cognitive theories, negative cognitions including negative attitudes
      towards the future are key factors associated with depressive disorder. We
      investigated the neural correlates of anticipation of emotional stimuli in
      patients with unipolar depression to reveal influences of future thinking on
      brain activity. We used functional magnetic resonance imaging (fMRI) to study 12
      female patients with stable antidepressant medication and 12 healthy women.
      Subjects were presented with positive, negative and neutral pictures that were
      announced by a congruent cue. Subjects were instructed to expect and subsequently
      watch the pictures. After scanning, subjects filled the Emotion Regulation
      Questionnaire (ERQ) to assess the regulation strategies suppression and
      reappraisal. Compared to the healthy control group, during expectation of
      negative vs. neutral or positive stimuli the patients showed significantly more
      activation within the sublenticular extended dorsal amygdala (SLEA) bilaterally
      but did not differ from controls upon expecting positive stimuli. Hamilton
      depression scores of the patients correlated positively with activation of the
      left and right ventral amygdala during expectation of negative stimuli.
      Furthermore, we found a negative correlation of ventral amygdala activation in
      the patients with reappraisal scores comprising the ability to limit emotional
      responding by re-interpreting emotion-eliciting situations. We interpret enhanced
      activation in the amygdala/SLEA as a possible consequence of altered future
      thinking in patients suffering from depression. Supporting cognitive theories,
      this finding does represent evidence that altered cognitions as potentially
      involved in expectation result in differences in brain activity.

PMID- 17010995
TI  - The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP)
      for mood disorders: double-blind, placebo-controlled studies.
AB  - Our previous study has shown the beneficial effects of the herbal medicine called
      Free and Easy Wanderer Plus (FEWP) as adjunctive therapy with carbamazepine (CBZ)
      in the 12-week treatment of bipolar disorders (Zhang ZJ, Kang WH, Tan QR, Li Q,
      Gao CG, Zhang FG, et al., Adjunctive herbal medicine with carbamazepine for
      bipolar disorders: a double-blind, randomized, placebo-controlled study. J
      Psychiatr Res; 2005). Here, we present follow-up data obtained from a
      continuation of the previously reported study. Treatment and clinical evaluation
      of bipolar patients (n=188) who had randomly received 12-week CBZ plus placebo
      (n=92) or CBZ plus FEWP (n=96) were extended to 26 weeks under double-blind
      condition. Patients in adjunctive FEWP showed a significantly lower overall
      discontinuation rate (31%) at endpoint compared to placebo (51%, p=0.009), and of
      15% in adjunctive FEWP discontinued due to intolerable side effects, markedly
      lower than those in placebo (28%, p=0.019). No difference in discontinuation for
      lack of efficacy and exacerbation was observed in the two groups. Patients
      receiving adjunctive FEWP had significantly fewer adverse side effects and lower
      serum levels of CBZ than those in placebo. A separate study was further conducted
      to evaluate the effectiveness of FEWP as monotherapy in depressed patients. A
      total of 87 unipolar and 62 bipolar depressed patients were randomly assigned to
      treatment with 36 g/day FEWP (n=86) or placebo (n=63) for 12 weeks under double
      blind condition. Efficacy was measured using the Hamilton Rating Scale for
      Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and
      Clinical Global Impression-Severity (CGI-S). Both unipolar and bipolar patients
      assigned to FEWP displayed significantly greater improvement on the three
      efficacy indices and significantly higher clinical response rate (74%) than those
      treated with placebo (42%, p<0.001) at endpoint. These results suggest that
      adjunctive FEWP improves tolerability of CBZ in the long-term use, which may be
      associated with the suppression of blood CBZ concentrations via herb-drug
      interactions. FEWP monotherapy may be also an effective alternative treatment for
      depressed conditions.

PMID- 17010994
TI  - Predictors of risk for relapse in patients with schizophrenia or schizoaffective
      disorder during olanzapine drug therapy.
AB  - PURPOSE: To evaluate the relationship of dose decrease, symptom worsening, and
      baseline covariates on subsequent relapse during olanzapine treatment in patients
      with schizophrenia or schizoaffective disorder. METHODS: In two 28-week,
      randomized, double-blind clinical trials, a Cox proportional hazards model was
      used to determine potential correlates of relapse (defined as > or =20% worsening
      on PANSS total and CGI-Severity 3) among patients (N=271) who responded to 8
      weeks of olanzapine treatment (10-20mg/day). Variables examined included:
      demographics, illness characteristics, baseline symptoms, symptom change, dose,
      adverse events, and functioning. RESULTS: Patients with a lower last dose
      relative to the preceding visit interval were 4 times more likely to relapse
      during that visit interval than other patients (p<.001). A similar finding was
      observed for a decrease in interval modal dose, although this variable was more
      predictive of relapse in the visit interval immediately following dose decrease
      (p=.027). In a subgroup analysis by gender, there was a significantly greater
      incidence of relapse in men with a dose decrease, whereas a dose decrease in
      women did not correlate with relapse. Relapse was also correlated with the
      emergence or worsening of a psychiatric adverse event during the same (p<.001)
      and preceding (p=.007) visit intervals, and with increased rating scale measures
      of psychopathology. The occurrence of a non-psychiatric adverse event was not
      associated with relapse. CONCLUSION: Dose decrease is a significant predictor of
      relapse in male but not female patients. Psychiatric adverse events also
      predicted relapse. Patients should be periodically reassessed to determine the
      need for maintenance treatment with appropriate dose.

PMID- 17010996
TI  - Comet assay for the detection of genotoxicity in blood cells of flounder
      (Paralichthys olivaceus) exposed to sediments and polycyclic aromatic
      hydrocarbons.
AB  - To investigate the genotoxic effect of marine sediments on aquatic organism,
      sediment samples were collected from 13 sites along the coast of Gwangyang Bay
      (Korea). Concentrations of polycyclic aromatic hydrocarbons (PAHs) in sediments
      were determined and the relationship between exposure of flounder blood cells to
      sediment extracts and DNA single-strand breakage in the blood cells was examined
      using the comet assay. Levels of DNA damage were proportionally increased by
      exposure concentration and the highest sediment-associated DNA damage was
      observed at the station showing the highest PAHs contamination. DNA damage in
      blood cells exposed to five types of PAHs (benzo[a]pyrene, fluoranthene,
      anthracene, pyrene and phenanthrene) and in flounder (Paralichthys olivaceus)
      exposed to benzo[a]pyrene (BaP) for 0, 2 and 4 days were assessed by measuring
      comet tail length. The tail lengths of five PAHs-exposed groups at 50 and 100 ppb
      were significantly different from the non-exposed group, and the genotoxic effect
      of BaP correlated with both concentration and duration of exposure. Throughout
      the study, significant differences in DNA breakage were recorded between cells
      exposed to sediment extracts or PAHs and non-exposed control. This study
      demonstrated the comet assay as a successful tool in monitoring contamination of
      marine sediments and assessing genotoxicity of PAHs in marine organisms, either
      in vitro or in vivo.

PMID- 17010997
TI  - Ecological status in the Ligurian Sea: the effect of coastline urbanisation and
      the importance of proper reference sites.
AB  - The assessment of the ecological status, as required by the Water Framework
      Directive (WFD), plays an important role in coastal zone management, but only a
      small number of ecological indices are applicable on rocky bottoms. In this
      study, we apply a previously defined ecological quality index based on the
      cartography of littoral and upper-sublittoral rocky-shore communities (CARLIT),
      based on the sensitivity of algae dominated communities to anthropogenic impacts
      along a moderate urban gradient. We also apply this index in four Marine
      Protected Areas (MPAs), proposed as reference sites at a regional scale. After
      comparing the outputs with water variables and other quality indices, we can
      affirm that (1) the CARLIT index is suitable to detect different kinds of
      anthropogenic pressures, that (2) the choice of proper reference sites is a focal
      point in the fulfilment of the WFD (Water Framework Directive) and that (3)
      historical data are important to define reference conditions and the degradation
      of ecological status.

PMID- 17010998
TI  - Benthic biodiversity indices versus salinity gradient in the southern Baltic Sea.
AB  - The need to assess the environmental status of marine and coastal waters
      according to the EU Water Framework Directive (WFD) encouraged the design of
      specific biotic indices to evaluate the response of benthic communities to human
      induced changes in water quality. In the present study three of these indices,
      the traditional Shannon Wiener Index (H') and the more recently published AMBI
      (AZTI' Marine Biotic Index) and BQI (Benthic Quality Index), were tested along a
      salinity gradient in the southern Baltic Sea. The comparison of the three indices
      demonstrates that in the southern Baltic Sea the ecological quality (EcoQ)
      classification based on macrozoobenthic communities as indicator greatly depends
      on the biotic index chosen. We found a significant positive relation between
      species number, H', BQI and salinity resulting in EcoQ status of "Bad", "Poor" or
      "Moderate" in areas with a salinity value below 10 psu. The AMBI was less
      dependent on salinity but appear to partly overestimate the EcoQ status.
      Presently none of these biotic indices appear to be adjusted for application in a
      gradient system as given in the southern Baltic Sea. A potential approach
      describing how to overcome this limitation is discussed.

PMID- 17010999
TI  - Avian-human influenza epidemic model.
AB  - A mathematical model is proposed to interpret the spread of avian influenza from
      the bird world to the human world. Our mathematical model warns that two types of
      the outbreak of avian influenza may occur if the humans do not prevent the spread
      of avian influenza. Moreover, it suggests that we cannot feel relieved although
      the total infected humans are kept at low level. In order to prevent spread of
      avian influenza in the human world, we must take the measures not only for the
      birds infected with avian influenza to exterminate but also for the humans
      infected with mutant avian influenza to quarantine when mutant avian influenza
      has already occurred. In particular, the latter measure is shown to be important
      to stop the second pandemic of avian influenza.

PMID- 17011000
TI  - A new approach to reconstruction models of dendritic branching patterns.
AB  - Quantitative models for characterising the detailed branching patterns of
      dendritic trees aim to explain these patterns either in terms of growth models
      based on principles of dendritic development or reconstruction models that
      describe an existing structure by means of a canonical set of elementary
      properties of dendritic morphology, which when incorporated into an algorithmic
      procedure will generate samples of dendrites that are statistically
      indistinguishable in both canonical and emergent features from those of the
      original sample of real neurons. This article introduces a conceptually new
      approach to reconstruction modelling based on the single assumption that
      dendritic segments are built from sequences of units of constant diameter, and
      that the distribution of the lengths of units of similar diameter is independent
      of location within a dendritic tree. This assumption in combination with non
      parametric methods for estimating univariate and multivariate probability
      densities leads to an algorithm that significantly reduces the number of basic
      parameters required to simulate dendritic morphology. It is not necessary to
      distinguish between stem and terminal segments or to specify daughter branch
      ratios or dendritic taper. The procedure of sampling probability densities
      conditioned on local morphological features eliminates the need, for example, to
      specify daughter branch ratios and dendritic taper since these emerge naturally
      as a consequence of the conditioning process. Thus several basic parameters of
      previous reconstruction algorithms become emergent parameters of the new
      reconstruction process. The new procedure was applied successfully to a sample of
      51 interneurons from lamina II/III of the spinal dorsal horn.

PMID- 17011001
TI  - Influence of nutrient preload on encapsulated macronutrient selection in European
      sea bass.
AB  - The sea bass is a teleost that is able to regulate its energy intake by selecting
      from pure macronutrient sources, although the regulatory mechanisms involved in
      this selection are unknown. Nutrient preloads are known to reduce food intake and
      modify macronutrient selection patterns in mammals, but no information is
      available on its effects in fish. The aim of the present work was to determine
      the effect of orally administered macronutrient preloads of protein (P), fat (F)
      or carbohydrate (CH) on the subsequent macronutrient selection, using for the
      purpose feed consisting of CH, P or F packaged separately in gelatin capsules.
      The macronutrient preloads left the total food intake unaltered, but caused
      differential changes in the pattern of macronutrient selection. The CH preload
      increased the selection of CH (39%) and decreased that of P (20%), independently
      of the fish's previous nutritional preferences. The F preload induced an F
      increase (32%) and a P decrease (18%) in P-preferring fish, but not in F
      preferring fish in which the macronutrient selection pattern remained unaffected.
      The P preload stimulated F selection by 42% in P-preferring fish, but left the
      macronutrient selection pattern unchanged in F-preferring fish. In conclusion,
      oral macronutrient preloads affected the pattern of macronutrient selection in
      fish, acting by post-ingestive mechanisms. The effect was influenced by the
      fish's previous nutritional preference and/or status, which could depend on its
      metabolic capacity.

PMID- 17011002
TI  - Increased expression of endothelin B receptor in static stretch exposed porcine
      mitral valve leaflets.
AB  - The aim of this study was to evaluate the effect of mechanical stretch on the
      expression of ET-1 and ET(A)- and ET(B)-receptors in porcine mitral valve
      leaflets. Leaflet segments from 10 porcine mitral valves were exposed to a static
      stretch load of 1.5 N for 3.5h in buffer at 37 degrees C together with matching
      control segments. Subsequently, the mRNA expression of ET-1, ET(A)-R and ET(B)-R
      was measured by real-time RT-PCR in the chordal insertion areas. The analyses
      showed an increased transcription of ET(B)-receptors in stretch-exposed leaflet
      segments compared to unstretched segments median 2.23 (quartiles 1.37 and 2.70)
      vs. median 1.56 (quartiles 1.38 and 2.17, P=0.03) whereas the mRNA expression of
      ET(A)-receptors (P=0.90) and ET-1 (P=0.51) remained unchanged. Stretch increased
      the expression of ET(B)-receptors in porcine mitral valve leaflets. The finding
      could lead to a better understanding of the pathogenesis of myxomatous mitral
      valve disease.

PMID- 17011003
TI  - Influence of aging on adrenal responsiveness in a population of eleven healthy
      beagles.
AB  - The present study aimed at investigating the effects of aging on the adrenal
      cortex response of cortisol and aldosterone in dogs. A population of healthy
      adult Beagles was evaluated twice at a five-year interval. At each evaluation,
      plasma basal cortisol and aldosterone, cortisol and aldosterone following ACTH
      stimulation, sodium, and potassium concentrations and arterial blood pressure
      were measured. We observed significantly (p<0.05) greater sodium, urea and
      creatinine concentrations with aging. Nevertheless urea and creatinine remained
      within our laboratory reference ranges. This study showed a highly significant
      age-related elevation of basal cortisol (p<0.01). Inversely, both aldosterone
      following ACTH-stimulation levels and difference between aldosterone following
      ACTH-stimulation and basal aldosterone values plummeted significantly (p<0.01)
      with aging. In conclusion, the evaluation of the adrenal cortex function in dogs
      should take in consideration the age of the individuals.

PMID- 17011004
TI  - Nigerian medical students are at risk for hepatitis B infection.
AB  - Medical students are exposed to blood and body fluids. This study was conducted
      to estimate the prevalence of hepatitis B virus (HBV) infection amongst medical
      students of the Lagos State University College of Medicine, Ikeja, Nigeria. Data
      were collected through a self-administered questionnaire and through blood
      analysis for hepatitis B surface antigen (HBsAg), hepatitis B 'e' antigen (HBeAg)
      as well as antibodies to the core (anti-HBc), surface (anti-HBs) and 'e' (anti
      HBe) antigens. Three hundred and thirteen of 325 students (96%) participated. The
      mean age was 24.3+/-3.98 years; 231 (74%) were pre-clinical students and 82 (26%)
      were in the clinical years of study. Only 8 (2.6%) had received three doses of
      vaccination against HBV. Eighty-one (26%) tested positive for anti-HBc, 10 (3.2%)
      were positive for HBsAg and 56 (17.9%) had anti-HBs antibodies. A significant
      relationship was found between students who had a positive history of hepatitis B
      in the family and anti-HBc (P=0.03). Age was also significantly associated with
      HBsAg (P=0.012). Two hundred and twenty-five (72%) students were susceptible to
      the infection and required vaccination. Most students at this medical school are
      susceptible to HBV infection and should be vaccinated.

PMID- 17011005
TI  - American tegumentary leishmaniasis: direct species identification of Leishmania
      in non-invasive clinical samples.
AB  - Species identification is highly relevant for improved prognosis and adequate
      treatment of American tegumentary leishmaniasis (ATL). PCR-based methods are
      available for this purpose but should be simplified to improve accessibility. As
      a first step in this process, this paper describes a simplified protocol for
      collection of clinical samples. Using samples from 44 Bolivian patients with
      confirmed ATL, we demonstrated that hsp70 PCR-RFLP on skin scrapings collected
      with a tooth pick allowed identification of the parasite species with a
      sensitivity of 95% and specificity of 100%. Our method should greatly facilitate
      individual patient management and epidemiological surveillance of ATL.

PMID- 17011006
TI  - Spatial effects favour the evolution of niche construction.
AB  - We present an individual-based, spatial implementation of an existing two-locus
      population genetic model of niche construction. Our analysis reveals that, across
      a broad range of conditions, niche-construction traits can drive themselves to
      fixation by simultaneously generating selection that favours 'recipient' trait
      alleles and linkage disequilibrium between niche-construction and recipient trait
      alleles. The effect of spatiality is key, since it is the local, resource
      mediated interaction between recipient and niche-constructing loci which gives
      rise to gene linkage. Spatial clustering effects point to a possible mechanism by
      which an initially rare recipient trait whose selection depends on niche
      construction could establish in an otherwise hostile environment. The same
      mechanism could also lead to the spread of an established niche-constructing
      colony. Similar phenomena are observed in the spatial modelling of two species
      'engineering webs'. Here, the activities of two niche-constructing species can
      combine to drive a particular recipient trait to fixation, or in certain
      circumstances, maintain the presence of polymorphisms through the preservation of
      otherwise deleterious alleles. This may have some relevance to ecosystem
      stability and the maintenance of genetic variation, where the frequencies of key
      resources are affected by the niche-constructing activities of more than one
      species. Our model suggests that the stability of multi-species webs in natural
      populations may increase as the complexity of species-environment interactions
      increases.

PMID- 17011007
TI  - Transfer and metabolism of paralytic shellfish poisoning from scallop (Chlamys
      nobilis) to spiny lobster (Panulirus stimpsoni).
AB  - The transfer and transformation of paralytic shellfish poisoning (PSP) from
      scallop Chlamys nobilis to spiny lobster Panulirus stimpsoni were investigated in
      the present study. The results demonstrate that transfer and transformation of
      PSP toxins occurred when Panulirus stimpsoni were fed with toxic viscera of
      Chlamys nobilis, but depurated with non-toxic squids. Additionally, only the
      lobster hepatopancreas were found to contain PSP, and the toxin profiles were the
      same with those in the viscera of the scallop, including carbamate toxins (GTX(1
      3)), N-sulfocarbamoyl toxins (C(1+2) and B(1)) and decarbamoyl toxins
      (dcGTX(2+3)). Unlike the lobster, the scallop contained more alpha than beta
      toxins. After being fed with toxic Chlamys nobili for 6 d, Panulirus stimpsoni
      selectively accumulated N-sulfocarbamoyl toxins with low toxicity. However, when
      they were depurated with non-toxic squid, N-sulfocarbamoyl toxins tended to
      transform into carbamate toxins with higher toxicity. The concentration of
      dcGTX(2+3) in Panulirus stimpsoni decreased significantly and wasn't detectable
      after depuration for 6 d, which was likely due to their initial low accumulation
      of toxins. These results reveal that PSP could be transferred and transformed in
      Crustaceans along the given food chain under the conditions of laboratory, but
      there are many questions remained to be solved, and the further studies should be
      carried out.

PMID- 17011008
TI  - Interaction of a plane progressive sound wave with a functionally graded
      spherical shell.
AB  - An exact analysis is carried out to study interaction of a time-harmonic plane
      progressive sound field with a radially inhomogeneous thick-walled elastic
      isotropic spherical shell suspended in and filled with compressible ideal fluid
      mediums. Using the laminated approximation method, a modal state equation with
      variable coefficients is set up in terms of appropriate displacement and stress
      functions and their spherical harmonics. Taylor's expansion theorem is then
      employed to obtain the solution to the modal state equation ultimately leading to
      calculation of a global transfer matrix. Numerical example is given for a water
      submerged/air-filled Aluminum/Zirconia elastic spherical sandwich shell
      containing a functionally graded interlayer and subjected to an incident
      progressive plane sound wave. The mechanical properties of the interlayer are
      assumed to vary smoothly and continuously across the thickness with the change of
      volume concentration of its constituents. The effect of incident wave frequency,
      thickness and compositional gradient of the interlayer on the form function
      amplitude and the average radiation force acting on the composite shell are
      examined. Limiting cases are considered and fair agreements with well-known
      solutions are established.

PMID- 17011009
TI  - Variable region 4 of SIV envelope correlates with rapid disease progression in
      morphine-exposed macaques infected with SIV/SHIV.
AB  - We analyzed the association between the evolution of the V3-V5 regions of env and
      disease progression in our SIV/SHIV macaque model of morphine dependence and
      AIDS. Previous studies revealed two distinct disease patterns--fast progression
      and normal progression. To determine the effect of the two distinct patterns of
      disease in the evolution of SIV/17E-Fr envelope, we analyzed env sequences from
      three morphine-dependent macaques that developed accelerated AIDS and three
      morphine-dependent macaques that developed AIDS at a slower rate and compared
      them to control macaques. Morphine-dependent animals exhibited a higher
      percentage of diversity in both plasma and CSF compartments within V4 when
      compared to controls. Divergence from the inoculum was significantly greater in
      the morphine group as compared to controls in CSF but not in plasma. We also
      found a direct correlation in V4 evolution and rapid disease progression. These
      results indicate that morphine dependence plays a role in the pathogenesis of
      SIV/SHIV infection and env evolution.

PMID- 17011011
TI  - Membrane embedded HIV-1 envelope on the surface of a virus-like particle elicits
      broader immune responses than soluble envelopes.
AB  - Virally regulated HIV-1 particles were expressed from DNA plasmids encoding Gag,
      protease, reverse transcriptase, Vpu, Tat, Rev, and Env. The sequences for
      integrase, Vpr, Vif, Nef, and the long terminal repeats (LTRs) were deleted.
      Mutations were engineered into the VLP genome to produce particles deficient in
      activities associated with viral reverse transcriptase, RNase H, and RNA
      packaging. Each plasmid efficiently secreted particles from primate cells in
      vitro and particles were purified from the supernatants and used as immunogens.
      Mice (BALB/c) were vaccinated intranasally (day 1 and weeks 3 and 6) with
      purified VLPs and the elicited immunity was compared to particles without Env
      (Gag(p55)), to soluble monomeric Env(gp120), or to soluble trimerized Env(gp140).
      Only mice vaccinated with VLPs had robust anti-Env cellular immunity. In
      contrast, all mice had high titer anti-Env serum antibody (IgG). However, VLP
      vaccinated mice had antisera that detected a broader number of linear Env
      peptides, had anti-Env mucosal IgA and IgG, as well as higher titers of serum
      neutralizing antibodies. VLPs elicited high titer antibodies that recognized
      linear regions in V4-C5 and the ectodomain of gp41, but did not recognize V3.
      These lentiviral VLPs are effective mucosal immunogens that elicit broader
      immunity against Env determinants in both the systemic and mucosal immune
      compartments than soluble forms of Env.

PMID- 17011010
TI  - Protection against polyoma virus-induced tumors is perforin-independent.
AB  - CD8 T cells are necessary for controlling tumors induced by mouse polyoma virus
      (PyV), but the effector mechanism(s) responsible have not been determined. We
      examined the PyV tumorigenicity in C57BL/6 mice mutated in Fas or carrying
      targeted disruptions in the perforin gene or in both TNF receptor type I and type
      II genes. Surprisingly, none of these mice developed tumors. Perforin/Fas double
      deficient radiation bone marrow chimeric mice were also resistant to PyV-induced
      tumors. Anti-PyV CD8 T cells in perforin-deficient mice were found not to differ
      from wild type mice with respect to phenotype, capacity to produce cytokines or
      maintenance of memory T cells, indicating that perforin does not modulate the PyV
      specific CD8 T cell response. In addition, virus was cleared and persisted to
      similar extents in wild type and perforin-deficient mice. In summary,
      perforin/granzyme exocytosis is not an essential effector pathway for protection
      against PyV infection or tumorigenesis.

PMID- 17011013
TI  - Rhodopsin-transducin coupling: role of the Galpha C-terminus in nucleotide
      exchange catalysis.
AB  - In the early steps of visual signal transduction, light-activated rhodopsin (R*)
      catalyzes GDP/GTP exchange in the heterotrimeric G protein (Galphabetagamma)
      transducin. We recently reported that the catalytic interaction involves two
      sequential steps. An initial docking between R* and Gbetagamma leads to
      conformational changes which make the C-terminus of Galpha (CTalpha) available
      for binding to R*. Binding of CTalpha by R* then triggers GDP/GTP exchange in the
      Galpha subunit. To further study this two-step mechanism, we investigated
      different single amino acid substitutions within CTalpha and discuss the effects
      of high affinity mutations on nucleotide exchange catalysis.

PMID- 17011012
TI  - Adeno-associated virus induces apoptosis during coinfection with adenovirus.
AB  - Adeno-associated virus (AAV) is a nonpathogenic parvovirus that efficiently
      replicates in the presence of adenovirus (Ad). Exogenous expression of the AAV
      replication proteins induces caspase-dependent apoptosis, but determining if AAV
      infection causes apoptosis during viral infection is complicated by Ad-mediated
      programmed cell death. To eliminate Ad-induced cytolysis, we used an E3
      adenoviral death protein (ADP) mutant, pm534. AAV and pm534-coinfected cells
      exhibited increased cell killing compared to pm534 alone. Relative to cells
      infected with Ad alone, AAV and wild-type Ad-infected cells displayed decreased
      ADP expression, increased cytolysis until the third day of the infection, and
      decreased cytolysis thereafter. Biochemical and morphological characteristics of
      apoptosis were observed during coinfections with AAV and pm534 or Ad, including a
      moderate degree of caspase activation that was not present during infections with
      pm534 or Ad alone. AAV coinfection also increased extracellular pH. These studies
      suggest that AAV induces caspase-dependent and caspase-independent apoptosis.

PMID- 17011014
TI  - Perceptual distortions of speed at low luminance: evidence inconsistent with a
      Bayesian account of speed encoding.
AB  - Our perception of speed has been shown to be distorted under a number of viewing
      conditions. Recently the well-known reduction of perceived speed at low contrast
      has led to Bayesian models of speed perception that account for these distortions
      with a slow speed 'prior'. To test the predictive, rather than the descriptive,
      power of the Bayesian approach we have investigated perceived speed at low
      luminance. Our results indicate that, for the mesopic and photopic range (0.13-30
      cd m(-2)) the perceived speed of lower luminance patterns is virtually unaffected
      at low speeds (<4 deg s(-1)) but is over-estimated at higher speeds (>4 deg s(
      1)). We show here that the results can be accounted for by an extension to a
      simple ratio model of speed encoding [Hammett, S. T., Champion, R. A., Morland,
      A. & Thompson, P. G. (2005). A ratio model of perceived speed in the human visual
      system. Proceedings of Royal Society B, 262, 2351-2356.] that takes account of
      known changes in neural responses as a function of luminance, contrast and
      temporal frequency. The results are not consistent with current Bayesian
      approaches to modelling speed encoding that postulate a slow speed prior.

PMID- 17011015
TI  - Comparative eco-toxicity of nanoscale TiO2, SiO2, and ZnO water suspensions.
AB  - The potential eco-toxicity of nanosized titanium dioxide (TiO(2)), silicon
      dioxide (SiO(2)), and zinc oxide (ZnO) water suspensions was investigated using
      Gram-positive Bacillus subtilis and Gram-negative Escherichia coli as test
      organisms. These three photosensitive nanomaterials were harmful to varying
      degrees, with antibacterial activity increasing with particle concentration.
      Antibacterial activity generally increased from SiO(2) to TiO(2) to ZnO, and B.
      subtilis was most susceptible to their effects. Advertised nanoparticle size did
      not correspond to true particle size. Apparently, aggregation produced similarly
      sized particles that had similar antibacterial activity at a given concentration.
      The presence of light was a significant factor under most conditions tested,
      presumably due to its role in promoting generation of reactive oxygen species
      (ROS). However, bacterial growth inhibition was also observed under dark
      conditions, indicating that undetermined mechanisms additional to photocatalytic
      ROS production were responsible for toxicity. These results highlight the need
      for caution during the use and disposal of such manufactured nanomaterials to
      prevent unintended environmental impacts, as well as the importance of further
      research on the mechanisms and factors that increase toxicity to enhance risk
      management.

PMID- 17011016
TI  - Enhanced biodegradation of mixed phenol and sodium salicylate by Pseudomonas
      putida in membrane contactors.
AB  - A polypropylene (PP) hollow fiber membrane contactor was used as a reactor to
      enhance the biodegradation of equimolar phenol and sodium salicylate (SA) by
      Pseudomonas putida CCRC 14365 at 30 degrees C and pH 7. Experiments were
      performed at a fixed initial cell density of 0.025 g/L and in the total substrate
      level range 5.32-63.8 mM. The degradation experiments by free cells were also
      studied for comparison. With pristine hydrophobic fibers, the degradation of SA
      was started only after phenol was completely consumed. Substrate inhibitory
      effect was avoided due to sufficiently low substrate levels in the cell medium;
      however, the biodegradation was time consuming. With ethanol-wetted fibers, both
      substrates were completely degraded much faster than the use of pristine fibers.
      Although the wetted fibers were unable to prevent movement of substrates through
      the pores, biofilm formed on the outer surfaces of the fibers could enhance the
      tolerance limit of substrate toxicity. This greatly extended the treatment range
      to high-level substrate mixtures, as long as the water was nearly neutral and
      free of concentrated inorganic salts.

PMID- 17011017
TI  - Solar photocatalytic degradation of reactive blue 4 using a Fresnel lens.
AB  - The heterogeneous photocatalytic degradation of reactive blue 4 dye (RB4)
      solutions under Fenton reagent and TiO(2) assisted by concentrated solar light
      irradiation using a Fresnel lens has been studied. Multivariate experimental
      design was applied to study the kinetic process. The efficiency of photocatalytic
      degradation was determined from the analysis of color and total organic carbon
      (TOC) removal. Factorial experimental design allowed to determine the influence
      of four parameters (pH and initial concentrations of TiO(2), Fe(II) and H(2)O(2))
      on the value of the decoloration kinetic rate constant. Experimental data were
      fitted using neural networks (NNs). The mathematical model reproduces
      experimental data within 86% of confidence and allows the simulation of the
      process for any value of parameters in the experimental range studied. Also, a
      measure of the saliency of the input variables was made based upon the connection
      weights of the neural networks, allowing the analysis of the relative relevance
      of each variable with respect to the others. Results showed that acidic pHs
      (pH=3.6) are preferred for the complete dye decoloration. The optimum catalyst
      concentration is 1.2g TiO(2)/l. The use of a low cost catalyst and its activation
      using a Fresnel lens to concentrate solar energy significantly accelerates the
      degradation process when compared with direct solar radiation alone and can offer
      an economical and practical alternative for the destruction of environmental
      organic compounds.

PMID- 17011019
TI  - Comparison of MTBE concentrations in groundwater of urban and nonurban areas in
      Germany.
AB  - The occurrence of the gasoline oxygenate methyl tert-butyl ether (MTBE) in
      groundwater samples from known fuel-contaminated sites (n=29 samples), nonurban
      (n=74) and urban sites (n=67) in Germany was investigated. The analyses revealed
      detection frequencies of 58% (contaminated sites), 24% (nonurban sites) and 63%
      (urban sites) at a detection limit of 0.01 microgL(-1). Median (maximum) MTBE
      concentrations were calculated for nonurban and urban samples as 0.18 microgL(-1)
      (2.2 microgL(-1)) and 0.06 microgL(-1) (48 microg L(-1)). The data from nonurban
      samples revealed MTBE detections mainly at public supply wells with higher
      pumping rates than monitoring wells. MTBE was more frequently detected in urban
      samples, most probably due to the higher atmospheric input and direct liquid
      emissions from motorways or gas stations. Higher concentrations above 1.0
      microgL(-1) in urban areas were found in wells located at industrial sites, where
      also a MTBE plume was accidentally detected during the study. The prevalence of
      MTBE in shallow aquifers was comparable to those in the USA.

PMID- 17011018
TI  - Potential phosphorus recovery in a WWTP with the BCFS process: interactions with
      the biological process.
AB  - The BCFS process was developed to optimize the activity of denitrifying and P
      removing bacteria. In this technology in combination with optimal operating
      conditions for biological nitrogen removal, chemical precipitation of phosphorus
      is used to ensure compliance with effluent standards regarding phosphorus. This
      work addresses the potential of the BCFS technology for phosphorus recovery and
      the interactions with the biological process. The TUD model calibrated for the
      Hardenberg WWTP was used. Nitrification was the biological process most
      influenced by the P stripper operation; however, further research is needed into
      the effect of limiting phosphate concentrations. Phosphate removal in the
      anaerobic reactor causes a decrease in the sludge poly-P content. The evaluation
      of the process operation under dynamic conditions showed that the P stripper use
      for phosphate recovery does not imply complicated control strategies. The use of
      the BCFS for phosphate recovery implies a change in the design philosophy not
      only to achieve the effluent requirements but also to maximize the anaerobic
      phosphate release and thereby recovery.

PMID- 17011020
TI  - Manganese-oxide-coated alumina: a promising sorbent for defluoridation of water.
AB  - In this study, adsorption potential of a new sorbent manganese-oxide-coated
      alumina (MOCA) was investigated for defluoridation of drinking water using batch
      and continuous mode experiments. The effects of different parameters such as pH,
      initial fluoride concentration and co-existing ions (usually present in
      groundwater sample) were studied to understand the adsorption behavior of the
      sorbent under various conditions. Optimum removal of fluoride ions occurred in a
      pH range of 4-7. Results of the present study indicate that fluoride adsorption
      rate and adsorption capacity of MOCA are far superior to that of activated
      alumina (AA), which was used as the base material for MOCA preparation. The MOCA
      can be effectively regenerated using 2.5% NaOH as eluent. The Langmuir
      equilibrium model was found to be suitable for describing the fluoride sorption
      on AA and MOCA. The maximum fluoride uptake capacity for MOCA and AA was found to
      be 2.85 and 1.08 mg g(-1), respectively. The kinetic results showed that the
      fluoride sorption to MOCA followed pseudo--second-order kinetics with a
      correlation coefficient greater than 0.98. The fluoride sorption capacity at
      breakthrough point for both the adsorbents was greatly influenced by bed depth. A
      bed depth service time (BDST) approach was adopted to describe the continuous
      flow system. The batch and column studies demonstrated the superiority of MOCA
      over AA in removing fluoride from the drinking water system.

PMID- 17011021
TI  - Comparison between the effects of aging and hyperoxia on glutathione redox state
      and protein mixed disulfides in Drosophila melanogaster.
AB  - The main purpose of this study was to determine whether experimental enhancement
      of oxidative stress by exposure to hyperoxia is an appropriate model for the
      acceleration of the normal aging process or for establishing a causal association
      between oxidative stress and aging. Insect tissues are directly exposed to
      ambient air via the tracheolar invaginations and are thus highly susceptible to
      oxidative stress under hyperoxic conditions. Amounts of glutathione (GSH),
      glutathione disulfide (GSSG) and protein mixed disulfides (PrSSG) were compared
      under normoxic and 100% ambient oxygen in males of two different strains of
      Drosophila melanogaster (Oregon R (WT) and y w strains). The reason for using two
      different strains was to preclude the effects of genetic background and to
      determine whether variations in longevity of the two strains are associated with
      resistance to oxidative stress. Amounts of GSSG and PrSSG increased, whereas
      GSH:GSSG ratios declined as a function of age in both strains. Under hyperoxia, y
      w flies did not exhibit an increase in GSSG amount or a decline in GSH:GSSG
      ratio, whereas WT flies showed a decline in GSH:GSSG ratio only during the later
      part of hyperoxic exposure. In neither strain there was a progressive increase in
      PrSSG amount under hyperoxia. Results indicate that hyperoxia (100% oxygen)
      neither reproduces nor accelerates the pattern of alterations in glutathione
      redox state and PrSSG content observed during aging under normoxic conditions,
      although some other indicators of oxidative stress may be affected.

PMID- 17011022
TI  - Correlation of the toxicity of organic compounds to tadpoles using the Abraham
      model.
AB  - The narcotic and lethal concentrations of organic compounds have been compiled
      for several tadpole species (Rana temporaria, Rana pipiens, Rana japonica,
      Xenopus laevis and Rana brevipoda porosa). The narcotic and lethal concentrations
      have been correlated using the Abraham solvation parameter model to yield an
      equation that can be used to predict the narcotic concentrations of additional
      nonpolar and polar narcotic compounds to R. temporaria, and a more general
      correlation that should be applicable to different species of tadpoles. The more
      general equation is based on 240 experimental data points. A training set of 123
      compounds could be fitted with the Abraham solvation parameters with R(2)=0.931
      and S.D.=0.343 log units. The training equation predicted the test set of 122
      values with AE=-0.022 log units, S.D.=0.300 log units and an average absolute
      error, AAE, of 0.227 log units. The structural features that are important in
      narcosis of tadpoles have been examined; it is concluded that hydrogen bond
      basicity reduces narcotic activity of compounds and that compound size increases
      narcotic activity. The solvation parameter model enables narcosis of tadpoles to
      be compared to various other biological processes and to physicochemical
      processes that might be used as models for narcosis.

PMID- 17011023
TI  - Do zebra mussels (Dreissena polymorpha) alter lake water chemistry in a way that
      favours Microcystis growth?
AB  - This study examined possible relationships between the presence of zebra mussels
      (Dreissena polymorpha) and Microcystis spp. abundance. Experiments were conducted
      in 12 microcosms designed to mimic shallow lake ecosystems. Fresh, aerated water
      with phytoplankton (pseudokirchneriella spp. and Microcystis spp.) was pumped
      into each microcosm daily to ensure zebra mussels were exposed to oxygen and
      food. Microcosms containing zebra mussels experienced significantly higher fluxes
      of nitrate (p=0.019) and lower fluxes of ortho-phosphate (p=0.047) into
      sediments. In a second experiment, water column nutrient concentrations were
      compared in microcosms with and without live zebra mussels. Consistent with
      results of the previous experiment, microcosms with zebra mussels had
      significantly less nitrate (p=0.023) and organic nitrogen (p=0.003) in the water
      column, while ammonium (p=0.074), phosphate (p=0.491), and dissolved organic
      carbon (p=0.820) in the water column were not different between microcosms with
      or without zebra mussels. Microcosms with zebra mussels also experienced a
      reduction in green algae (pseudokirchneriella) (p<0.001) and an increase in
      abundance of Microcystis (p<0.001) relative to microcosms without zebra mussels.
      In an experiment without zebra mussels, nutrient ratios (N/P) were manipulated to
      determine potential links between N/P and relative abundance of each
      phytoplankton. Manipulation of N/P was intended to mimic differences observed in
      microcosms with and without zebra mussels in the previous experiment. Low N/P
      (mimicking microcosms with zebra mussels) was related to an increase in
      Microcystis (p<0.001) and Microcystis/Pseudokirchneriella biovolume (p<0.001). It
      is this shift in N/P, and possibly some level of selective feeding, that is
      believed to have driven changes in the relative abundance of Microcystis. In
      lakes invaded by zebra mussels, alterations in the processing of nitrogen and
      phosphorus could contribute to the re-emergence of Microcystis blooms.

PMID- 17011024
TI  - The biogenic volatile organic compounds emission inventory in France: application
      to plant ecosystems in the Berre-Marseilles area (France).
AB  - An inventory describing the fluxes of volatile organic compounds (VOCs), isoprene
      and monoterpenes, and other VOCs (OVOCs) from the biosphere to the atmosphere,
      has been constructed within the framework of the ESCOMPTE project (fiEld
      experimentS to COnstrain Models of atmospheric Pollution and Transport of
      Emissions). The area concerned, located around Berre-Marseilles, is a
      Mediterranean region frequently subject to high ozone concentrations. The
      inventory has been developed using a fine scale land use database for the year
      1999, forest composition statistics, emission potentials from individual plant
      species, biomass distribution, temperature and light intensity. The seasonal
      variations in emission potentials and biomass were also taken into account.
      Hourly meteorological data for 1999 were calculated from ALADIN data and these
      were used to predict the hourly isoprene, monoterpene and OVOC fluxes for the
      area on a 1 kmx1 km spatial grid. Estimates of annual biogenic isoprene,
      monoterpene and OVOC fluxes for the reference year 1999 were 20.6, 38.9 and 13.3
      kt, respectively, Quercus pubescens, Quercus ilex, Pinus halepensis and garrigue
      vegetation are the dominant emitting species of the area. VOC emissions from
      vegetation in this region contribute approximately 94% to the NMVOC (non-methane
      volatile organic compounds) of natural origin and are of the same order of
      magnitude as NMVOC emissions from anthropogenic sources. These results complete
      the global ESCOMPTE database needed to make an efficient strategy for
      tropospheric ozone reduction policy.

PMID- 17011025
TI  - Short- and medium-term effects of three fire fighting chemicals on the properties
      of a burnt soil.
AB  - The impact of three fire fighting chemicals (FFC) on 11 chemical soil properties
      and on soil recovery (0-2 cm depth) was evaluated 1, 30, 90 and 365 days after a
      prescribed fire. Five treatments were considered: unburnt soil (US) and burnt
      soil with 2 l m(-2) of water alone (BS) or mixed with the foaming agent
      Auxquimica RFC-88 at 1% (BS+Fo), Firesorb at 1.5% (BS+Fi) and FR Cross ammonium
      polyphosphate at 20% (BS+Ap). At t=1 day, soil pH increases in the order
      US<BS</=BS+Fo, BS+Fi<BS+Ap, which was most likely due to the accumulation of
      ashes, the reduction of organic acids and the cations supplied by FFC. In all
      burnt treatments, soil pH remained significantly higher than in US up until t=90
      days. SOM richness remained similar and constant until t=90 days in all plots,
      but, probably due to fire-triggered erosion, at t=365 days it was significantly
      lower in BS+Ap (C, N), BS and BS+Fo (C) than in US. Immediately after the fire,
      soil delta(15)N decreased in all burnt soils (significatively in BS+Ap) due to
      the inputs of (15)N depleted ashes from leguminous vegetation. Compared with US,
      soil delta(15)N increased significantly in all burnt plots between t=90 days (30
      days in BS+Ap) and t=365 days, suggesting a medium-term fire-triggered increment
      of N outputs ((15)N depleted). As is habitually the case, there was a transient
      post-fire increase of NH(4)(+)-N levels (significative for BS+FFC plots) that
      lasted for 30 (BS, BS+Fo and BS+Fi) to 90 days (BS+Ap). The high initial NH(4)(+)
      N levels in BS+Ap (200x that of US; 9-18x those of BS, BS+Fo and BS+Fi), and its
      persistence can delay the post-fire vegetation recovery due to the toxicity of
      NH(4)(+) to seeds and seedlings. NO(3)-N levels changed significantly only in
      BS+Ap between t=30 and t=90 days due to the nitrification of its large NH(4)(+)-N
      pool. Except in BS+Ap, whose soil P levels were 70-140x (t=1 days) and 10-20x
      (t=365 days) higher than in the other treatments, available P content in BS and
      BS+FFC was not significatively higher than in US. The concentrations of available
      cations in BS and BS+FFC were higher (not always significatively, except for K)
      than in US until t=90 days, likely due to ashes- and FFC-derived cations.
      Contrarily to divalent cations, monovalent cations (more soluble and easily
      leached) decreased slowly until t=90 days.

PMID- 17011026
TI  - Optical anisotropy of alcian blue-stained acid glycosaminoglycans.
AB  - Optical anisotropy as dispersion of birefringence (DB) (birefringence studied for
      light of different wavelengths) and linear dichroism (LD) (selective absorption
      of polarized light) in stained substrates reflects their macromolecular
      orientation states. Birefringence interference colors of alcian blue (AB)-stained
      glycosaminoglycans (GAG) and glycoconjugates observed with polarization
      microscopy have been found to vary, although their staining characteristics under
      unpolarized light are practically the same. We investigated the optical
      anisotropy of GAG-AB and some glycoconjugate-AB complexes used as standards, to
      provide a basis for interpreting results for AB-stained materials in situ.
      Filamentous preparations of hyaluronic acid (HA), chondroitinsulfates,
      proteoglycans, and a mucus sulfoglycoconjugate were studied. Anomalous DB
      (birefringence sign changing with the wavelength of the incident light) was
      generally observed, but LD was seen only in the AB-HA complex. LD simultaneous to
      anomalous DB characteristics on the AB-HA complex were assumed to be caused by a
      maximally oriented helical conformation of the HA. For the other AB-GAG studied,
      the optical anisotropic characteristics were suggestive of some degree of folding
      of their chains into a tertiary structure. The profiles of the anomalous DB
      curves for the AB-stained sulfoglycoconjugate differed from those of the other
      materials, probably due to different organization of its dye-binding sites.

PMID- 17011027
TI  - Developmental control in animals and a biological role for DNA charge transfer.
AB  - A model is developed based on data from diverse lines of inquiry, describing the
      possible role of charge transfer in the timing and coordination of DNA
      replication and gene expression in eukaryotic cells. Emphasis is placed on a
      possible electrical process which participates in the simultaneous base-pair
      opening in many regions of DNA preceding replication, and a similar coordination
      of gene expression by simultaneous generation of base-pair openings around
      promoter and transcriptional start sites. This process could have the character
      of an ultradian biological clock. There is no specific evidence for such a
      process, but the argument is presented that such a process is neither unphysical
      nor unbiological, and its postulation would act as a first-iteration road map for
      explaining the coordinated nature of eukaryotic organism development.

PMID- 17011028
TI  - Rational design of hydrogels for tissue engineering: impact of physical factors
      on cell behavior.
AB  - When designing suitable biomaterials for tissue-engineering applications,
      biological and chemical parameters are frequently taken into account, while the
      equally important physical design variables have often been neglected. For a
      rational design of biomaterials, however, all variables influencing cell function
      and tissue morphogenesis have to be considered. This review will stress the
      development of cross-linked hydrogels and outline the impact of their physical
      properties on cell function and tissue morphogenesis. In the first part, the
      principles of cellular mechanosensitivity, as well as the influence of substrate
      mechanics on cell behavior, will be discussed. Afterwards, methods to
      characterize the mechanical properties of biomaterials will be presented. The
      subsequent chapters will address hydrogels that allow for the control of their
      physical qualities followed by a discussion of their use in tissue-engineering
      applications.

PMID- 17011029
TI  - Endostatin variations in childhood acute lymphoblastic leukaemia--comparison with
      basic fibroblast growth factor and vascular endothelial growth factor.
AB  - Angiogenic factors such as basic fibroblast growth factor (bFGF) or vascular
      endothelial growth factor (VEGF) were previously studied in childhood acute
      lymphoblastic leukaemia (ALL) but little is known concerning the anti-angiogenic
      response in ALL. At diagnosis, the plasma levels of the anti-angiogenic factor
      endostatin were significantly higher in 33 children with ALL than in controls
      (median values 17.7 and 7.6 ng/ml, respectively, p=0.0192) but no relationship
      was observed with plasma bFGF or VEGF levels. The highest levels were observed in
      patients with an hyperdiploid karyotype. Expression of mRNA for collagen
      XVIII/endostatin in lymphoblasts was detected in 19/24 cases but protein
      secretion was found only in 14/28 supernatants of cultured lymphoblasts. No
      direct relationship appeared between secretion of endostatin by lymphoblasts and
      plasma levels. In addition, endostatin levels remained elevated in remission,
      suggesting that endostatin could have a stromal origin as well. No prognostic
      value of plasma endostatin could be assessed. In conclusion, the present data
      indicate that an anti-angiogenic response is observed in some ALL children, but
      its physiopathological importance remains to be established.

PMID- 17011030
TI  - Tyk2 mutation homologous to V617F Jak2 is not found in essential
      thrombocythaemia, although it induces constitutive signaling and growth factor
      independence.
AB  - A single somatic mutation, V617F, in the pseudokinase domain of the Jak2 is the
      primary cause of many chronic myeloproliferative diseases. As valine 617 of Jak2
      is conserved as valine 678 of Tyk2, we examined the effect of a homologous
      mutation in Tyk2 (V678F Tyk2) on cell growth. V678F Tyk2 augmented the
      transcriptional activity of Stat3 and Stat5. The expression of V678F Tyk2 in
      Ba/F3 cells induced autonomous cell growth and showed hyper-responsiveness to IL
      3. Although V678F Tyk2 might cause MPD, no cases of ET patients lacking the V617F
      Jak2 mutation harbored the Tyk2 mutation.

PMID- 17011031
TI  - AML M1 presenting with recurrent acute large arterial vessel thromboembolism.
AB  - Acute leukemia may be associated with coagulopathy, predominantly severe bleeding
      diathesis caused by disseminated intravascular coagulation (DIC) and/or
      hyperfibrinolysis. Disordered hemostasis is characteristic for acute
      promyelocytic leukemia (APL, FAB M3). However, thromboembolic events such as
      arterial occlusion localized to the large vessels at presentation is very rare
      and almost exclusively linked to APL. We report a case of severe recurrent acute
      arterial thromboembolism at presentation in AML FAB M1. Most likely, the ischemic
      events in our patient resulted from leukemia as the thrombus material included
      many leukemic blasts. The thrombotic complications resulted in leg amputation in
      this patient. Despite leg amputation just a couple of hours before and extremely
      high infectious risk of the patient, chemotherapy was administered. The clinical
      course of cessation of the ischemic events and a fast reduction of the blasts in
      the peripheral blood smear after chemotherapeutic treatment of the patient
      outlines the importance and life saving role of early chemotherapy even under
      adverse circumstances.

PMID- 17011032
TI  - Ethical issues concerning consent in obtaining children's reports on their
      experience of violence.

PMID- 17011033
TI  - Compassion fatigue, burnout, and compassion satisfaction: Implications for
      retention of workers.

PMID- 17011034
TI  - Sensitivity of juvenile freshwater crayfish Cherax destructor (Decapoda:
      Parastacidae) to trace metals.
AB  - Juvenile Cherax destructor was investigated as a potential test species for
      toxicity testing of trace metals in Australian freshwater systems. Adult male and
      female C. destructor were bred in the laboratory to obtain 4-week old juveniles,
      which were used in the toxicity tests. Animals were exposed to a range of
      concentrations of the trace metals ions copper (377-1275 microg/L), cadmium (377
      1275 microg/L), nickel (300-1013 mg/L) and iron (36-168 mg/L) in static-renewal
      96-h bioassays. The 96-h LC50 value for cadmium was 379, 494 microg/L for copper,
      50 mg/L for iron and 327 mg/L for nickel demonstrating a decreasing toxicity of
      these metals to C. destructor. Comparison of LC50 values for metals for this
      species with those for other aquatic organisms reveals that C. destructor is less
      sensitive to trace metals than most other tested species.

PMID- 17011035
TI  - Generation of llama single-domain antibodies against methotrexate, a prototypical
      hapten.
AB  - Single-domain antibodies specific to methotrexate (MTX) were obtained after
      immunization of one llama (Llama glama). Specific VHH domains (V-D-J-REGION) were
      selected by panning from an immune-llama library using phage display technology.
      The antibody fragments specific to MTX were purified from Escherichia coli (C41
      strain) periplasm by immobilized metal affinity chromatography with an expression
      level of around 10mg/L. A single band around 16,000Da corresponding to VHH
      fragments was found after analysis by SDS-PAGE and Western blotting, while
      competition ELISA demonstrated selective binding to soluble MTX. Surface plasmon
      resonance (SPR) analysis showed that anti-MTX VHH domains had affinities in the
      nanomolar range (29-515nM) to MTX-serum albumin conjugates. The genes encoding
      anti-MTX VHH were found by IMGT/V-QUEST to be similar to the previously reported
      llama and human IGHV germline genes. The V-D and D-J junction rearrangements in
      the seven anti-MTX CDR3 sequences indicate that they were originated from three
      distinct progenitor B cells. Our results demonstrate that camelid single-domain
      antibodies are capable of high affinity binding to low molecular weight
      hydrosoluble haptens. Furthermore, these anti-MTX VHH give new insights on how
      the antigen binding repertoire of llama single-domain antibody can provide
      combining sites to haptens in the absence of a VL. This type of single-domain
      antibodies offers advantages compared to murine recombinant antibodies in terms
      of production rate and sequence similarity to the human IGHV3 subgroup genes.

PMID- 17011036
TI  - Synthesis, DNA-binding and photocleavage studies of ruthenium(II) complex with 2
      (3'-phenoxyphenyl)imidazo[4,5-f][1,10]phenanthroline.
AB  - A new polypyridyl ligand MPPIP {MPPIP=2-(3'-phenoxyphenyl)imidazo[4,5-f]
      [1,10]phenanthroline} and its ruthenium(II) complexes, [Ru(bpy)(2)MPPIP](2+) (1)
      (bpy=2,2'-bipyridine) and [Ru(phen)(2)MPPIP](2+) (2) (phen=1,10-phenanthroline)
      have been synthesized and characterized. The binding of the two complexes to calf
      thymus DNA (CT-DNA) has been investigated with spectrophotometric methods,
      viscosity measurements, as well as equilibrium dialysis and circular dichroism
      spectroscopy. The results suggest that both complexes bind to CT-DNA through
      intercalation, and enantioselectively interact with CT-DNA in a way. However,
      complex 2 is a much better candidate as an enantioselective binder to CT-DNA than
      complex 1. When irradiated at 365nm, both complexes have also been found to
      promote the photocleavage of plasmid pBR322 DNA.

PMID- 17011037
TI  - Near edge X-ray absorption fine structure spectroscopy (NEXAFS) of pigment
      protein complexes: peridinin-chlorophyll a protein (PCP) of Amphidinium carterae.
AB  - Peridinin-chlorophyll a protein (PCP) is a unique water soluble antenna complex
      that employs the carotenoid peridinin as the main light-harvesting pigment. In
      the present study the near edge X-ray absorption fine structure (NEXAFS) spectrum
      of PCP was recorded at the carbon K-edge. Additionally, the NEXAFS spectra of the
      constituent pigments, chlorophyll a and peridinin, were measured. The energies of
      the lowest unoccupied molecular levels of these pigments appearing in the carbon
      NEXAFS spectrum were resolved. Individual contributions of the pigments and the
      protein to the measured NEXAFS spectrum of PCP were determined using a "building
      block" approach combining NEXAFS spectra of the pigments and the amino acids
      constituting the PCP apoprotein. The results suggest that absorption changes of
      the pigments in the carbon near K-edge region can be resolved following
      excitation using a suitable visible pump laser pulse. Consequently, it may be
      possible to study excitation energy transfer processes involving "optically dark"
      states of carotenoids in pigment-protein complexes by soft X-ray probe optical
      pump double resonance spectroscopy (XODR).

PMID- 17011038
TI  - Dissecting drug and vehicle metabolic effects in rats by a metabonomic approach.
AB  - A combined application of high resolution (1)H NMR spectroscopy and multivariate
      statistical techniques focused on establishing a consistent statistical approach
      to metabonomic studies was tested. The data reduction, which is preliminary to
      the application of multivariate analysis to NMR spectra, was carried out by means
      of two complementary methods: pure Pattern Recognition (PR) and Assigned Signal
      Analysis (ASA). The simultaneous use of both approaches allowed us to obtain
      additional information in the analysis of metabonomic data, compared to the use
      of PR alone. This additional information consists in the possibility of a
      biochemical interpretation of the effects induced by treatment with xenobiotics,
      such as drugs or drug vehicles, on the metabolic networks of the systems under
      investigation. This approach allowed us to ascertain that a single-dose treatment
      with ST1959 vehicled by Sesame oil affects the production of hepatic glucose
      associated to an increment of the amino acid ketogenic process.

PMID- 17011039
TI  - Calculation of transmission coefficients for some permeant molecules in human red
      cell and resting axolemma squid axon membranes.
AB  - Quantum mechanical calculations of transmission coefficients for some permeant
      molecules across the human red cell and resting axolemma squid axon membranes are
      carried out. The calculations depend on (i) the molecular weight of the molecule
      and (ii) the depth and width of the potential well of the membrane. In most cases
      good agreement between calculated and experimental values is found.

PMID- 17011040
TI  - Sensitization of surfactants on the chemiluminescence reaction of fluorescein
      isothiocyanate labeled proteins.
AB  - The effect of surfactants on fluorescein isothiocyanate (FITC)-bovine serum
      albumin (BSA)-hypochlorite (ClO(-)), FITC-human serum albumin (HSA)-ClO(-), FITC
      ovoconalbumin (OVA)-ClO(-), FITC-hemoglobin (Hb)-ClO(-) systems were investigated
      with chemiluminescence method by the reversed phase flow injection. It was found
      that the chemiluminescence (CL) intensity of each system was increased greatly in
      the presence of cationic surfactants. Cethyltrimethylammonium bromide (CTAB) is
      the optimal surfactant of these systems. The optimal conditions of the CL
      reaction and the optimal concentration of CTAB were examined and the function of
      cationic surfactant CTAB on the CL reaction was also discussed.

PMID- 17011041
TI  - Investigation of Alzheimer's disease-related pathology in community dwelling
      older subjects who committed suicide.
AB  - BACKGROUND: Older people have a higher risk of completed suicide than any other
      age group worldwide. The contribution of neurodegenerative disease to this risk
      remains controversial. AIMS: To investigate prevalence of Alzheimer's disease
      related (AD) pathology in older suicide victims. METHODS: Ratings of AD pathology
      using Braak and CERAD protocols were compared in 143 community-dwelling suicide
      victims aged 65 years or more and 59 motor vehicle accident victims autopsied at
      the request of an Australian Coroner's Court. RESULTS: There were no significant
      differences in plaque score or neurofibrillary tangle staging between suicide and
      control groups. None of the subjects with a history of dementia had
      neuropathologically confirmed AD. CONCLUSIONS: Our study is the second and
      largest investigation of the prevalence of AD neuropathology in the elderly
      suicide population. Unlike the previous study, we did not find an increased
      prevalence of AD neuropathology despite a history of dementia in 6.3%,
      implicating other pathologies such as Lewy Body or Vascular dementia in the
      aetiology of dementia in elderly suicide victims.

PMID- 17011042
TI  - Maternity blues in Athens, Greece: a study during the first 3 days after
      delivery.
AB  - BACKGROUND: Although maternity blues have been studied in many countries
      worldwide the factors that influence the occurrence of this clinical entity are
      not well understood. The purpose of this study was to investigate the prevalence,
      time course and symptomatology of maternity blues in a Greek urban environment as
      well as the relation of maternity blues with certain clinical and
      sociodemographic factors. METHOD: A study of a sample of 402 women that were
      recruited during the first day after delivery. Each woman completed the
      Kennerley's Blues Questionnaire on a daily basis for the first 3 days of
      puerpartum. Clinical and sociodemographic data were obtained through
      questionnaires and personal interview. RESULTS: 179 (44.5%) women experienced
      severe maternity blues during the first 3 days after delivery. Delivery by
      caesarian section (P=0.006), stressful events during pregnancy (P=0.02),
      depressive feelings the last month prior to delivery (P=0.002), anxiety on the
      day of delivery (P=0.001) and hypochondriasis (P=0.001) were the factors that
      were found to relate significantly to maternity blues. CONCLUSION: The women's
      emotional condition prior and after delivery, delivery via caesarotomy, as well
      as fears concerning somatic health had strong impact on the occurrence of
      maternity blues.

PMID- 17011043
TI  - Birth month and depressive and suicidal symptoms in an elderly Australian sample
      born in the Southern or Northern Hemisphere.
AB  - We examined the relationship between season of birth and depressive and suicidal
      symptoms among 859 elderly outpatients. Date and country of birth were recorded
      for each participant. Those in utero during the Northern or Southern Hemisphere
      flu peak were expected to show the highest depressive and suicidal symptoms.
      Hypotheses were partially supported.

PMID- 17011044
TI  - Genomic cloning of feline Fas ligand gene and characterization of the
      transcription regulatory region.
AB  - The feline Fas ligand gene was molecularly cloned from a feline genomic library
      and its genomic organization was determined. The feline Fas ligand gene contained
      four exons and spanned approximately 10 kb in the genome, and thus had the same
      structure as the human Fas ligand gene. The promoter region of the feline Fas
      ligand gene was further characterized by deletion mapping. The region between
      nucleotides -459 and -172 relative to the ATG codon was essential for the
      promoter activity when transfected into human and feline lymphoid cells. The
      characterization of the feline Fas ligand gene in the present study will be
      useful for further investigations of the regulatory mechanism of feline Fas
      ligand expression.

PMID- 17011045
TI  - Cytokine expression in leucocytes and gut cells of rainbow trout, Oncorhynchus
      mykiss Walbaum, induced by probiotics.
AB  - Understanding how the various host cells respond to probiotic bacteria in vitro
      may provide important insight into elaborate immune responses triggered by
      beneficial bacteria. The aim of this study was to investigate the detailed
      pattern of the mRNA expression of cytokines (IL-1beta, IL-8, TNF-alpha and TGF
      beta) in head kidney (HK) leucocytes and gut cells isolated from rainbow trout
      (Oncorhynchus mykiss Walbaum) after co-culturing with live probiotics. HK
      leucocytes and gut cells adjusted to 5 x 10(6) and 2 x 10(6) ml(-1),
      respectively, in L-15 medium containing 25% decomplemented FCS and 300 mg l(-1) L
      glutamine were co-cultured with Carnobacterium maltaromaticum B26 and C.
      divergens B33 at an multiplicity of infection of 25 for 6 and 12 h. Quantitative
      real-time reverse transcriptase polymerase chain reaction using SYBR Green I was
      employed to determine the mRNA expression of studied genes. Although neither
      probiotic strains significantly induced mRNA of the cytokines in gut cells,
      expression ratios of IL-1beta and TNF-alpha of HK cells were significantly
      higher, suggesting that these bacteria can stimulate innate immunity in rainbow
      trout.

PMID- 17011046
TI  - Maturation of murine bone marrow-derived dendritic cells with poly(I:C) produces
      altered TLR-9 expression and response to CpG DNA.
AB  - Although poly(I:C) and LPS induced differential dendritic cell (DC) cytokine
      profiles and toll-like receptor (TLR) expression, all were capable of causing
      phenotypic and functional DC maturation. Both LPS and poly(I:C) downregulated TLR
      4/MD-2 expression on DCs. Although poly(I:C) highly upregulated their cell
      surface TLR-9 expression, LPS upregulated the intracellular TLR-9 expression. LPS
      treated DCs could not produce IL-12p70 in response to subsequent both LPS- and
      CpG DNA-stimulation. On the other hand, poly(I:C)-treated DCs retained to produce
      IL-12p70 by subsequent CpG DNA-stimulation, while subsequent LPS-stimulation did
      not induce IL-12p70 production. Chloroquine, inhibitor of endosomal maturation,
      completely inhibited cytokine production of LPS-treated DCs as well as
      unstimulated control in response to subsequent CpG DNA-stimulation, while it
      failed to delete the IL-12p40 and IL-10 production in poly(I:C)-treated DCs.
      These data suggest that poly(I:C) may induce a novel DC phenotype that preserves
      the capacity of cytokine production to subsequent CpG DNA-stimulation.

PMID- 17011047
TI  - In vivo modulation of LPS-induced alterations in brain and peripheral cytokines
      and HPA axis activity by cannabinoids.
AB  - This study investigated cannabinoid receptor-mediated regulation of brain and
      peripheral cytokines in vivo. The cannabinoid receptor agonist, HU210 attenuated
      lipopolysaccharide (LPS)-induced increases in IL-1beta and TNFalpha in rat brain
      and IL-1beta, TNFalpha, IL-6 and IFNgamma in plasma. The CB(1) receptor
      antagonist, SR141716A, attenuated the immunosupressive effects of HU210 on IL
      1beta, but not TNFalpha. SR141716A or the CB(2) receptor antagonist, SR144528,
      alone attenuated LPS-induced cytokine increases. LPS and/or cannabinoids also
      reduced circulating lymphocyte numbers and increased corticosterone levels. These
      data provide evidence for modulation of pro-inflammatory cytokines in vivo by
      cannabinoid receptors and inform the development of cannabinoids for
      neuroinflammatory disorders.

PMID- 17011048
TI  - CD4+CD25+FoxP3+ T lymphocytes fail to suppress myelin basic protein-induced
      proliferation in patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disorder directed against self antigens
      of the central nervous system. CD4(+)CD25(+)FoxP3(+) regulatory T cell (T(reg))
      mediated suppression is an essential mechanism of self-tolerance. We studied
      whether changes in the suppressive function of a mixture of CD25(high) and
      CD25(intemediate) expressing T(reg) cells in myelin basic protein (MBP)-induced
      proliferation occurred in untreated MS patients. Suppression of MBP-induced
      proliferation was observed in 13 out of 29 (45%) MS patients; this was
      significantly (p<0.05) less compared with 17 out of 19 (89%) healthy individuals.
      Relative T(reg) counts was significantly increased in MS patients (mean+/-S.D.;
      20+/-8%) compared with healthy individuals (15+/-5%). These findings suggest that
      impaired T(reg) function may be involved in pathogenesis of MS.

PMID- 17011049
TI  - Expression and distribution of Toll-like receptors in the brain during murine
      neurocysticercosis.
AB  - In a mouse model of neurocysticercosis, the expression and distribution of Toll
      like receptors (TLRs) was investigated by using both gene array analyses and in
      situ immunofluorescence microscopy (IF). In the normal uninfected brain, mRNA of
      all the TLRs are constitutively expressed albeit TLR5, TLR7, TLR8 and TLR9 to a
      lesser extent. In these animals, however, expression of TLR1, TLR3, TLR4 and TLR9
      proteins was not detected. In contrast, parasite infection increased both gene
      and protein level expression of all the TLRs several fold except TLR5 where only
      the mRNA was upregulated. Importantly, TLRs were differentially distributed among
      various central nervous system (CNS) cell types and infiltrating leukocytes. TLR2
      was almost exclusively localized to nervous tissue cells, particularly
      astrocytes, while TLR1 and TLR9 proteins were essentially limited to infiltrating
      leukocytes. All other TLRs tested were detected in both CNS and immune cell
      types. Interestingly, ependymal cells and neurofilaments of the cerebellar white
      matter of infected mice exhibited a substantial upregulation of TLR7 and TLR8
      proteins respectively. These data provide a comprehensive analysis of TLR
      expression in the normal and parasite infected brain and suggest a role for TLRs
      in the interplay of immune cells and CNS cells during infection.

PMID- 17011051
TI  - Use of reverse transcription loop-mediated isothermal amplification for the
      detection of Plum pox virus.
AB  - A one step, accelerated reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) procedure was developed for the detection of Plum pox
      virus (PPV). The six primers required for accelerated RT-LAMP were designed using
      a conserved region in the C-terminus of the coat protein coding region of PPV. RT
      LAMP was used to detect isolates of five strains of PPV including the strains D,
      M, EA, C, and W. The virus was detected reliably in both infected herbaceous and
      woody hosts. RT-LAMP was compared to real-time RT-PCR with SYBR Green I and
      melting curve analysis, using serial dilutions of total RNA extracts. Similar
      sensitivities were observed, except that real-time RT-PCR was more consistent at
      lower template concentrations. The purity of the FIP and BIP primers affected the
      efficiency of the reaction, and incubation time and template concentration
      affected the ladder-like pattern observed after agarose gel electrophoresis.
      Although PPV could be detected after 30min of incubation at 63 degrees C, a
      longer incubation time was required for lower concentrations of the target. RT
      LAMP is a very sensitive, low cost diagnostic tool that should be of value in
      more accurate determination of the distribution of PPV. This should assist in
      preventing further spread of this devastating virus.

PMID- 17011050
TI  - The schizophrenic faces of PICK1.
AB  - Schizophrenia is a grave psychiatric disorder with psychotic symptoms and an
      enigmatic etiology. Family studies have strongly indicated that genetic risk
      factors have a role in this disease. Recent findings, together with previously
      established evidence, highlight the PDZ-domain-containing protein interacting
      with C-kinase 1 (PICK1) as a promising candidate for a schizophrenia
      susceptibility gene. Here, we outline possible molecular mechanisms, discuss
      clinical case-studies that indicate an unexpected role of PICK1 in schizophrenia
      and discuss potential avenues for pharmacological manipulation of PICK1.

PMID- 17011052
TI  - Silencing shrimp white spot syndrome virus (WSSV) genes by siRNA.
AB  - White spot syndrome virus (WSSV) is a major shrimp pathogen causing large
      economic losses all over the world. So far, however, there is no efficient
      approach to control this virus. RNA interference (RNAi), which has been applied
      to silence virus genes in eukaryotic organisms. In this investigation, a specific
      21bp short interfering RNA (vp28-siRNA) targeting a major envelope protein gene
      (vp28) of WSSV was used to induce gene silencing in vivo in Penaeus japonicus
      shrimp. It was found that the transcription and expression of vp28 gene were
      silenced by the sequence-specific vp28-siRNA. However, the RNAi effect
      disappeared or significantly weakened even if one-nucleotide mutation existed in
      the vp28-siRNA. As revealed by quantitative PCR, the vp28-siRNA caused a
      significant reduction in viral DNA production of WSSV-infected shrimp. When
      treated with the vp28-siRNA, WSSV-infected shrimp had a reduced mortality rate.
      After three injections of the vp28-siRNA, the virus was completely eradicated
      from WSSV-infected shrimp. These findings suggest that RNAi is capable of
      silencing sequence-specific genes of WSSV and might constitute a new therapeutic
      strategy for WSSV infection in shrimp.

PMID- 17011053
TI  - First reproductive experience persistently affects spatial reference and working
      memory in the mother and these effects are not due to pregnancy or 'mothering'
      alone.
AB  - Pregnancy and motherhood are life-altering events that result in a number of
      hormonal, neural and behavioral changes in the mother. Motherhood has been shown
      to influence spatial learning and memory performance of the mother. In turn new
      research has shown that reproductive experience (number of times pregnant and
      mothered) plays a significant role on spatial learning and memory performance.
      How long these changes persist after weaning and the role of pregnancy and/or
      mothering on these changes have yet to be fully investigated. The present study
      aimed to determine whether enhanced spatial working and/or reference memory in
      the mother is evident long after weaning and whether these effects are due, in
      part, to pregnancy or 'mothering' alone. Five groups of age-matched rats:
      multiparous, primiparous, nulliparous, pregnant-only and sensitized rats were
      tested approximately 1 month after weaning/pup-exposure, or 55 days after birth,
      on the spatial working/reference version of the radial arm maze. Results show
      that regardless of error type (reference or working memory errors), primiparous
      rats make fewer errors compared to multi- and nulli-parous rats, with a trend to
      enhanced memory compared to sensitized rats. In addition, pregnant-only rats
      completed the task on significantly fewer days than primiparous, multiparous,
      nulliparous and sensitized rats. Clearly the combination of first pregnancy and
      first mothering experience has a significant impact on hippocampus-dependent
      learning and memory performance in the mother.

PMID- 17011054
TI  - The serial reaction time task in the rat: effects of D1 and D2 dopamine-receptor
      antagonists.
AB  - Sequential behaviour, probably reflecting procedural learning, has intensively
      been investigated in humans and monkeys using so-called serial reaction time
      tasks (SRTT), where serial stimuli are either presented in a random or sequential
      fashion. Learning of sequences is typically inferred from faster reaction times
      to such sequences as compared to random blocks of stimuli. Work with such tasks
      has shown that sequential behaviour seems to be mediated by specific brain
      systems, including the basal ganglia and the neurotransmitter dopamine. We have
      recently developed a rat version of the human serial reaction time task, in which
      rats have to respond to visual stimuli in one of four spatial locations by nose
      poking in order to obtain food reward under a fixed ratio schedule (FR13). Here,
      we used a test version where random and sequential condition phases (10 min each)
      were alternated within-sessions. In support of our previous work, we found that
      well-trained (i.e. skilled) rats display superior performance under sequential
      than random conditions, namely, faster reaction times and higher response
      accuracies. Furthermore, we investigated the effects of selective dopamine
      receptor blockade, by systemically administering SKF 83566, a D1 antagonist (.05
      .15 mg/kg), or raclopride, a D2 antagonist (.05-.20 mg/kg), in two separate
      experiments. Both antagonists impaired responding to the conditioned visual
      stimuli in a dose-related way, i.e. they decreased, or even blocked, nose-poke
      rates. In those rats, which kept responding, the speeding of reaction times
      during sequential conditions was no longer observed with the D1 antagonist,
      whereas the enhancements in accuracy were preserved, or even enhanced as compared
      to vehicle. The D2 antagonist also impaired instrumental behaviour, but did not
      alter sequence effects on accuracy or reaction times. In contrast to responses to
      the conditioned stimuli, reaction times to the unconditioned stimuli (food
      pellets) were not substantially affected by either drug. These results are
      discussed with respect to methodological factors, and the possible role of
      dopamine for instrumental behaviour, in general, and sequential behaviour, in
      specific.

PMID- 17011055
TI  - The bactericidal agent triclosan modulates thyroid hormone-associated gene
      expression and disrupts postembryonic anuran development.
AB  - We investigated whether exposure to environmentally relevant concentrations of
      the bactericidal agent, triclosan, induces changes in the thyroid hormone
      mediated process of metamorphosis of the North American bullfrog, Rana
      catesbeiana and alters the expression profile of thyroid hormone receptor (TR)
      alpha and beta, basic transcription element binding protein (BTEB) and
      proliferating nuclear cell antigen (PCNA) gene transcripts. Premetamorphic
      tadpoles were immersed in environmentally relevant concentrations of triclosan
      and injected with 1 x 10(-11)mol/g body weight 3,5,3'-triiodothyronine (T3) or
      vehicle control. Morphometric measurements and steady-state mRNA levels obtained
      by quantitative polymerase chain reaction were determined. mRNA abundance was
      also examined in Xenopus laevis XTC-2 cells treated with triclosan and/or 10nM
      T3. Tadpoles pretreated with triclosan concentrations as low as 0.15+/-0.03
      microg/L for 4 days showed increased hindlimb development and a decrease in total
      body weight following T3 administration. Triclosan exposure also resulted in
      decreased T3-mediated TRbeta mRNA expression in the tadpole tail fin and
      increased levels of PCNA transcript in the brain within 48 h of T3 treatment
      whereas TRalpha was unaffected [corrected] Triclosan alone altered thyroid
      hormone receptor alpha transcript levels in the brain of premetamorphic tadpoles
      and induced a transient weight loss. In XTC-2 cells, exposure to T3 plus nominal
      concentrations of triclosan as low as 0.03 microg/L for 24h resulted in altered
      thyroid hormone receptor mRNA expression. Exposure to low levels of triclosan
      disrupts thyroid hormone-associated gene expression and can alter the rate of
      thyroid hormone-mediated postembryonic anuran development.

PMID- 17011056
TI  - Through V2, not V1 receptor relating to endogenous opiate peptides, arginine
      vasopressin in periaqueductal gray regulates antinociception in the rat.
AB  - Our previous study has proven that central arginine vasopressin (AVP) plays an
      important role in antinociception, and pain stimulation raises AVP concentration
      in the periaqueductal gray (PAG). The nociceptive effect of AVP in PAG was
      investigated in the rat. The results showed that microinjection of AVP into PAG
      increased pain threshold, whereas microinjection of V2 receptor antagonist
      d(CH2)5[d-Ile2, Ile4, Ala9-NH2]AVP into PAG decreased pain threshold in a dose
      dependent manner, but local administration of V1 receptor antagonist
      d(CH2)5Tyr(Me)AVP did not change pain threshold; Pain stimulation elevated AVP,
      Leucine-enkephalin (L-Ek), Methionine-enkephalin (M-Ek) and beta-endorphin (beta
      Ep), not dynorphinA(1-13) (DynA(1-13)) concentrations in PAG perfuse liquid; PAG
      pre-treatment with naloxone, an opiate receptor antagonist or V2 receptor
      antagonist completely reversed AVP-induced increase in pain threshold, however,
      PAG pre-treatment with V1 receptor antagonist did not influence this effect of
      AVP administration. The data suggest that AVP in the PAG, through V2 rather than
      V1 receptor, regulates antinociception, which progress relates to enkephalin and
      endorphin.

PMID- 17011057
TI  - Do calcium sensitizers affect right ventricular functions in patients with
      chronic heart failure?
AB  - Calcium sensitizers also improve cardiac function by increasing the contraction
      of the myocardium without significantly increasing intracellular calcium levels.
      Although right ventricular function is an important role for better cardiac
      global function, there is no study about effects of levosimendan on right
      ventricular function measured by tissue Doppler imaging. The aim of the present
      study was to evaluate changes of myocardial properties in patients with
      idiopathic dilated cardiomyopathy using tissue Doppler imaging after levosimendan
      infusion. This tissue Doppler study shows that levosimendan also affects
      myocardial especially systolic waves of right ventricle and those of left
      ventricle.

PMID- 17011058
TI  - Efficacy and tolerability of concurrent weekly low dose cisplatin during
      radiation treatment of localised muscle invasive bladder transitional cell
      carcinoma: a report of two sequential Phase II studies from the Trans Tasman
      Radiation Oncology Group.
AB  - BACKGROUND AND PURPOSE: To determine the feasibility, toxicity, and clinical
      effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with
      definitive radiation in the treatment of localised muscle invasive bladder
      cancer. PATIENTS AND METHODS: In January 1997 the Trans Tasman Radiation Oncology
      Group embarked on a Phase II study (TROG 97.01) of weekly cisplatin (35 mg/m(2) x
      7 doses) plus radiation to a dose of 63 Gy over 7 weeks. Following an interim
      toxicity analysis, the dose intensity of cisplatin was reduced to 6 cycles and
      the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second
      study (TROG 99.06). A total of 113 patients were enrolled. RESULTS: Acute grade 3
      urinary toxicity occurred in 23% of the patients. Acute grade 4 pelvic toxicity
      was not seen. Thirty-eight patients (33%) experienced grade 3 or 4 cisplatin
      related toxicities with 15 patients (12%) requiring significant dose
      modification. The reduced dose intensity in Study 99.06 improved tolerability.
      Incidence of significant late morbidity was low (6%). Seventy-nine patients (70%)
      achieved complete remission at the 6 month cystoscopic assessment. Local invasive
      recurrence was seen in 11 of the 79 patients (14%). In 18 patients (16%) isolated
      superficial TCC/CIS were detected (6 months and beyond). The local control rate
      was 45% with a functional bladder being retained in 69 of the 113 patients (61%).
      RFS and DSS at 5 years were 33% and 50%, respectively. CONCLUSION: Our two
      sequential Phase II studies have shown that concurrent chemoradiation using
      weekly cisplatin in the management of localised invasive bladder TCC is feasible
      and reasonably well tolerated. This approach is currently being investigated
      further in a randomised study.

PMID- 17011059
TI  - Preliminary study of certain serotypes, genetic and antimicrobial resistance
      profiles of verotoxigenic Escherichia coli (VTEC) isolated in Bosnia and Germany
      from cattle or pigs and their products.
AB  - The aim of this study was to gather more information on the spread of VTEC
      serotypes, genetic profiles and resistance patterns from pigs or pork and from
      cattle or beef in different areas, and to improve detection of the source of
      outbreaks with a wider data pool. Of 130 Escherichia coli samples isolated from a
      cattle slaughter house and beef retail products in Sarajevo, Bosnia and
      Herzegovina (BiH), seven were identified as verotoxigenic (VTEC). In comparison,
      22 VTEC of 264 E. coli isolates were isolated from bovine faeces (14) and beef
      products (8) from Germany. Furthermore 23 VTEC of 76 isolates were identified
      from pig carcasses (10), faeces (9) and pork products (4) from Germany. Gene
      detection and serotyping were carried out in our laboratory and in the National
      Reference Laboratory. Antimicrobial resistance was tested with the dilution
      method in microtitre plates. All porcine isolates belonged to serotypes thus far
      not associated with human disease. Bovine VTEC were either serotypes commonly
      associated with human diseases (O157:H7, O103:H2, O157:H-) or rare serotypes. One
      serotype (O96:H19) was found only in isolates from Sarajevo. Most German VTEC,
      especially those of porcine origin, had only vtx2 genes, whereas all Bosnian
      isolates had vtx1 and vtx2 genes. The eae gene was found only in "classical" VTEC
      serotypes. All 52 VTEC (100%) investigated were resistant to the three
      sulfonamides tested; porcine isolates were mainly resistant to oxytetracycline
      (43%) and chlortetracycline (37%), bovine isolates mainly to
      trimethoprim/sulfamethoxazole and ampicillin (10% each). If sulfonamide
      resistances are disregarded, more than half (53.8%) of porcine VTEC were
      multiresistant and one-fourth (25%) of German bovine isolates, but none of the
      Bosnian bovine isolates. The results show the considerable spread of resistances
      in VTEC. These results also point out the necessity of gathering data from
      different geographical areas in order to be able to identify typical local
      variations in serotypes or gene expression and thus to trace human infections
      more quickly to their source.

PMID- 17011060
TI  - Spleen plays an important role in the induction of accelerated blood clearance of
      PEGylated liposomes.
AB  - It is well known that steric stabilization of the surface of liposomes by a
      polyethyleneglycol (PEG) conjugated lipid results in reduced recognition of the
      liposomes by the cells of the mononuclear phagocyte system and consequently
      extended circulation times of the liposomes (t1/2 approximately 20 h in rat).
      Recently, we reported on the "accelerated blood clearance (ABC) phenomenon",
      causing PEGylated liposomes to be cleared very rapidly from the circulation upon
      repeated injection. We also reported that abundant binding of IgM, secreted into
      the blood stream after the first dose and, to PEGylated liposomes, plays an
      essential role in the induction of the ABC phenomenon. Spleen is well known to
      play a central role in the immune reaction and to produce IgM following a
      bacterial infection. The aim of the present study was to determine whether spleen
      contributes to the induction of the ABC phenomenon and to unravel its role in the
      phenomenon. In rats that were splenectomized (surgical removal of spleen) prior
      to the first injection of liposomes (0.001 micromol phospholipids/kg), the ABC
      phenomenon was totally abolished. In these rats serum IgM concentrations as well
      as the amounts of IgM bound to PEGylated liposomes were substantially reduced.
      Splenectomy attenuated the ABC phenomenon when performed until 3 days post-first
      injection. Removal of the spleen 4 days post-first injection left the ABC
      phenomenon unchanged. This finding indicates that the immune reaction in the
      spleen against the PEGylated liposomes occurs during at least 2-3 days following
      the first administration and then IgM reactive to PEGylated liposomes is
      produced. The present study proves that the spleen plays a critical role in the
      induction phase of the ABC phenomenon. For effective clinical application, many
      liposomal drug formulations will require multiple injections. The ABC phenomenon
      described in this and several preceding papers therefore has important
      implications for the development and evaluation of therapeutically useful
      liposomal formulations requiring multiple-dose administration.

PMID- 17011061
TI  - Combined effects of ethanol and L-menthol on hairless rat stratum corneum
      investigated by synchrotron X-ray diffraction.
AB  - Synchrotron X-ray diffraction was employed to evaluate the effect of ethanol and
      l-menthol on lipid arrangements in the stratum corneum of hairless rats. Two
      sharp diffractions (S=2.40 and S=2.67, corresponding to spacing of 0.417 nm and
      0.374 nm respectively) were observed on the broad hump peak derived from soft
      keratin. To assist in understanding the effects of treatment with ethanol and l
      menthol, an abundance ration of lipid hydrocarbon chain packing index (R(H/O))
      was defined as R(H/O)=(Peak area at S=2.40 nm(-1))/(Peak area at S=2.67 nm(-1)).
      When ethanol was applied to the stratum corneum the intensities of diffraction
      peaks declined slightly. The R(H/O) values observed were not affected by
      variations in ethanol concentrations in the range 0-40% (w/w). The R(H/O) values
      did not change even when treatment with ethanol (40%, w/w) was extended to 8 h.
      These results suggested that lipid arrangements in the stratum corneum were not
      affected by ethanol. On the other hand, exposure of the stratum corneum to 2%
      (w/w) L-menthol caused a significant decrease in R(H/O) value. It was shown that
      L-menthol was dispersed through the stratum corneum, intruded mainly into
      hexagonal hydrocarbon chain packing, and disrupted the regular organization of
      these structures.

PMID- 17011062
TI  - Increased prevalence of VNTR III of the insulin gene in women with gestational
      diabetes mellitus (GDM).
AB  - OBJECTIVE: The VNTR polymorphism in the promoter region of the insulin gene (INS
      VNTR) affects transcription rate and has been associated with insulin resistance
      and DM2. Gestational diabetes mellitus (GDM) is a multifactorial disorder, where
      both impaired insulin secretion and action may be involved. The aim of the study
      was to examine the distribution of the INS-VNTRs in women with GDM and to
      investigate possible associations with features of beta cell function and
      glycaemic control in this population. METHODS: One hundred and sixty-one women
      with GDM and 111 normal pregnant women (n) were genotyped for INS-VNTR during the
      24th-32nd pregnancy week. Glucose and insulin levels were determined during the
      diagnostic OGTT. The majority of the previous GDM women were also examined at 3-6
      months post-partum. RESULTS: VNTR class III/III genotype was significantly more
      frequent in the GDM group 8.7% versus 2.7%, p=0.02 giving an OR of 3.97 (1.1
      14.29). An increased frequency of the VNTR class III allele was found in those
      GDM women who required insulin for treatment compared to those controlled with
      diet alone (12.4% versus 4%, p<0.001). Basal insulin levels tended to be lower in
      GDM women homozygous for the class III allele without reaching statistical
      significance (p=0.09). CONCLUSIONS: The INS-VNTR class III is more frequent in
      women who develop GDM, and may be associated with decreased ability of the beta
      cell to meet the increased insulin requirements as reflected by the need for
      insulin supplementation for adequate glycaemic control.

PMID- 17011063
TI  - Satisfaction with the access to the health services of the people with chronic
      conditions in Estonia.
AB  - After the implementation of the primary health care reform in Estonia, most of
      chronic conditions are managed by family doctors (FD) in collaboration with
      specialists. Although the general population has demonstrated the increase in
      satisfaction with health care after the reform, it has been questioned if people
      with chronic diseases have been left on a more disadvantaged position in the new
      system with some restrictions in the access to specialists. OBJECTIVE: To
      investigate the satisfaction of people with chronic conditions with the access to
      the health services and compare them to those who did not have a chronic illness.
      METHOD: In November 2005, a random sample of Estonian residents aged 15-74 were
      personally interviewed using structured questionnaires (n=1446), 29% of them
      reported to have a chronic illness. RESULTS: The people with chronic conditions
      were less satisfied with the access to the health services. They were more
      satisfied with their family doctors, but less with the health insurance system
      and they often reported their problems in seeing the specialist. Compared to
      other respondents, the people with chronic conditions visited their FDs and
      specialists more often, but no significant differences were found between their
      waiting times to see the FD or a specialist. CONCLUSION: In Estonia, the people
      with chronic conditions do not have organisational barriers in their access to
      the health services. As frequent users of health services, they perceive the
      shortages of the health system more obviously than the rest of the population and
      it may reflect their satisfaction with the different aspects of the health system
      as well as the access to the health services.

PMID- 17011064
TI  - Two-photon microscopes and in vivo multiphoton tomographs--powerful diagnostic
      tools for tissue engineering and drug delivery.
AB  - Near-infrared multiphoton microscopes and in vivo femtosecond laser tomographs
      are novel powerful diagnostic tools for intra-tissue drug screening and high
      resolution structural imaging applicable to many areas of biomedical research.
      Deep tissue cells and extracellular matrix (ECM) compartments can be visualized
      in situ with submicron resolution without the need for tissue processing. In
      particular, the reduced fluorescent coenzyme NAD(P)H, flavoproteins, keratin,
      melanin, and elastin are detected by two-photon excited autofluorescence, whereas
      myosin, tubulin and the ECM protein collagen can be imaged additionally by second
      harmonic generation (SHG). Therefore, these innovative multiphoton technologies
      have been used to probe architecture and state of a variety of native tissues, as
      well as of tissue-engineered constructs, giving insights on the interaction
      between scaffolds and seeded cells in vitro prior implantation. Moreover, non
      invasive 4-D multiphoton tomographs are employed in clinical studies to examine
      the diffusion behavior, the intra-tissue accumulation of topically applied
      cosmetic and pharmaceutical components, and their interaction with skin cells.

PMID- 17011065
TI  - Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and
      gemcitabine in the multimodality treatment of unresectable stage IIIB non-small
      cell lung cancer.
AB  - BACKGROUND: To evaluate feasibility and safety of induction three-drugs
      combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC.
      PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three
      courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2)
      and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without
      distant progressive disease were then treated with radiotherapy and concurrent
      weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy
      treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients
      were enrolled. Grade 3+ hematological and non-hematological toxicity during the
      induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical
      Response or Stable Disease was recorded and these patients underwent to
      concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological
      toxicities were 8.2% in this group. Further response was observed in 66% of
      patients. Overall median survival time was 17.8 months, with a 3-year survival
      rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio
      chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is
      feasible and safe.

PMID- 17011066
TI  - Assessment of molecular events in squamous and non-squamous cell lung carcinoma.
AB  - Although considerable knowledge exists on the tumor biology of lung cancer, there
      is still a need to assess molecular events for the clinical management of the
      disease. We studied the pattern of chromosomal imbalances in 45 non-small cell
      lung carcinomas (NSCLC) by comparative genomic hybridization (CGH) and correlated
      the results with clinicopathological features including immunohistochemical (IHC)
      expression of the epidermal growth factor receptor (EGFR). Twenty-one tumors were
      squamous cell carcinomas (SCC) and 24 non-squamous cell lung carcinomas (NSCC)
      comprising 9 adenocarcinomas (ADC), 9 large cell carcinomas (LCC), 4 sarcomatoid
      carcinomas and 2 adenosquamous carcinomas. The mean number of individual
      imbalances was 7.1 for SCC (mean gains, 3.8; mean losses, 3.4) and 6.4 for NSCC
      (mean gains, 4.5; mean losses, 1.9). Several individual imbalances correlated
      significantly with increasing number of imbalances, that were +1q, -3p, +3q, -5q,
      -8p, +8q, +7p, +12p, and +14q. Altogether, the most frequent imbalances were +3q
      (49%), +5p (49%), -5q (36%), +8q (29%), -8p (24%), -3p (22%), +7p (22%), +12p
      (22%), +14q (20%), +18p (20%), +1q (18%), and +7q (18%). Among these, +3q and
      +18p correlated significantly with SCC, and +5p and +14q with NSCC. Remarkably,
      overlapping imbalances included +3q26, +7p11 in SCC and +1q21, +3q24, +12p11, and
      +14q12 in NSCC. EGFR expression was higher in SCC than in NSCC and correlated
      with +3q in the entire series. In addition, +12p correlated significantly with
      disease progress with the exception of nodal involvement in NSCC as well as with
      disease progress, regardless of nodal involvement, in the entire series. In
      conclusion, the present study contributes to the molecular biological
      characterization of NSCLC histological subtypes and through evaluation of
      molecular events to the recently emergent focus on novel markers for lung cancer
      treatment.

PMID- 17011067
TI  - Clinicopathologic features and prognostic implications of epidermal growth factor
      receptor (EGFR) gene copy number and protein expression in non-small cell lung
      cancer.
AB  - Increased epidermal growth factor receptor (EGFR) gene copy numbers and mutations
      predict sensitivity to EGFR tyrosine kinase inhibitor in non-small cell lung
      cancer (NSCLC). However, the clinicopathologic features of EGFR gene copy status
      in NSCLC remain unclear. We retrospectively analyzed 262 cases of NSCLC,
      including 135 squamous cell carcinomas (SCC) and 112 adenocarcinomas (ADC), for
      which paraffin blocks of the resected primary lung mass were available. None had
      received EGFR-targeted therapy. EGFR gene copy number was evaluated using
      fluorescence in situ hybridization (FISH), and EGFR expression was determined
      immunohistochemically using a tissue microarray. A high EGFR gene copy (EGFR FISH
      positive) was found in 30.2% of the cases (amplification in 11.1% and high
      polysomy in 19.1%). There was no significant difference in EGFR FISH status with
      respect to SCC and ADC histology. The EGFR FISH-positive rate was higher in non
      smokers than in smokers in the multivariate analysis (p=0.012). EGFR expression
      was significantly associated with a high EGFR gene copy and SCC histology
      (p=0.000). In the univariate survival analysis, EGFR FISH-positivity predicted
      worse survival in SCC (p=0.059), especially stage I SCC (p=0.04). EGFR
      amplification was associated with a shorter survival in node-positive SCC
      (p=0.015). However, the EGFR gene copy number or protein expression had no
      influence on the prognosis of ADC. In conclusion, the EGFR FISH-positive rate in
      Korean patients with NSCLC was similar to rates in Western populations, unlike
      the higher frequencies of EGFR mutation in East Asians. A high EGFR gene copy
      number was significantly more common in non-smokers, as were EGFR mutations. A
      high EGFR gene copy number predicted worse survival in SCC; therefore, the
      prognostic implications of the EGFR gene and protein should be analyzed in the
      context of histology and staging in NSCLC.

PMID- 17011068
TI  - A phase II trial of fractionated irinotecan plus carboplatin for previously
      untreated extensive-disease small cell lung cancer.
AB  - PURPOSE: Irinotecan plus cisplatin has been previously documented to be effective
      in the treatment of extensive-disease small cell lung cancer (ED-SCLC). This
      study was undertaken to investigate the efficacy and feasibility of combination
      chemotherapy of irinotecan and carboplatin in previously untreated ED-SCLC.
      PATIENTS AND METHODS: From December 2002 to October 2005, 39 patients with
      previously untreated ED-SCLC were enrolled. Patients were treated with irinotecan
      (50mg/m(2) IV on days 1, 8, and 15) and carboplatin (target AUC=5 IV on day 1)
      every 4 weeks for up to six cycles. RESULTS: Thirty-four patients (87.2%) were
      male and the median age was 65 years. ECOG performance status was 0-1 in 20
      (51.3%) patients and 2 in 19 (48.7%) patients. The median number of chemotherapy
      cycles was six (range: 1-6 cycles). Thirty-five patients were assessable for
      response evaluation. The overall response rate was 69.2% (1 CR, 26 PR) under the
      intent-to-treat analysis. After a median follow-up of 22.7 months, the median
      time to progression was 6.4 months (95% confidence interval [CI]: 5.7-7.1 months)
      and median overall survival was 11.0 months (95% CI: 9.9-12.0 months). The
      estimated 1-year survival rate was 42.5%. In terms of toxicities, Grade 3/4
      neutropenia and thrombocytopenia occurred in eight (25.6%) and five (15.4%)
      patients, respectively. Grade 3/4 non-hematologic toxicities included diarrhea
      (10.3%), anorexia (7.7%), infection (10.3%), and neutropenic fever (12.8%). There
      was one treatment-related death due to superimposed infection on the broncho
      pleural fistula. CONCLUSION: The combination chemotherapy of irinotecan and
      carboplatin was effective and tolerable in previously untreated ED-SCLC patients.

PMID- 17011069
TI  - Have we overstated the tropical biodiversity crisis?
AB  - Tropical forests are the most biologically diverse and ecologically complex of
      terrestrial ecosystems, and are disappearing at alarming rates. It has long been
      suggested that rapid forest loss and degradation in the tropics, if unabated,
      could ultimately precipitate a wave of species extinctions, perhaps comparable to
      mass extinction events in the geological history of the Earth. However, a
      vigorous debate has erupted following a study by Wright and Muller-Landau that
      challenges the notion of large-scale tropical extinctions, at least over the next
      century. Here, I summarize this controversy and describe how the debate is
      stimulating a serious examination of the causes and biological consequences of
      future tropical deforestation.

PMID- 17011070
TI  - Ensemble forecasting of species distributions.
AB  - Concern over implications of climate change for biodiversity has led to the use
      of bioclimatic models to forecast the range shifts of species under future
      climate-change scenarios. Recent studies have demonstrated that projections by
      alternative models can be so variable as to compromise their usefulness for
      guiding policy decisions. Here, we advocate the use of multiple models within an
      ensemble forecasting framework and describe alternative approaches to the
      analysis of bioclimatic ensembles, including bounding box, consensus and
      probabilistic techniques. We argue that, although improved accuracy can be
      delivered through the traditional tasks of trying to build better models with
      improved data, more robust forecasts can also be achieved if ensemble forecasts
      are produced and analysed appropriately.

PMID- 17011071
TI  - Combined application of conservative transport modelling and compound-specific
      carbon isotope analyses to assess in situ attenuation of benzene, toluene, and o
      xylene.
AB  - In recent years, compound specific isotope analyses (CSIA) have developed into
      one of the most powerful tools for the quantification of in situ biodegradation
      of organic contaminants. In this approach, the calculation of the extent of
      biodegradation of organic contaminants in aquifers is usually based on the
      Rayleigh equation, and thus neglects physical transport processes such as
      dispersion that contribute to contaminant dilution in aquifers. Here we combine
      compound specific isotope analyses with a conservative transport model to study
      the attenuation of aromatic hydrocarbons at a former gasworks site. The
      conservative transport model was first used to simulate concentration reductions
      caused by dilution at wells downgradient of a BTEX source. In a second step, the
      diluted concentrations, together with the available stable carbon isotope ratios
      and carbon fractionation factors for benzene, toluene and o-xylene were applied
      in the Rayleigh equation to quantify the degree of biodegradation at each of
      those wells. At the investigated site, where other attenuation processes such as
      sorption and volatilisation were proven to be negligible, the combined approach
      is recommended for benzene, which represents a compound for which the effect of
      biodegradation is comparable to or less than the effect of dilution. As
      demonstrated for toluene and o-xylene, the application of the Rayleigh equation
      alone is sufficient if dilution can be proved to be insignificant in comparison
      to biodegradation. The analysis also suggests that the source width and the
      position of the observation wells relative to the plume center line are
      significantly related to the degree of dilution.

PMID- 17011072
TI  - Delayed fluid resuscitation in hemorrhagic shock induces proinflammatory cytokine
      response.
AB  - STUDY OBJECTIVE: This study is designed to determine the effects of delayed fluid
      resuscitation on the hemodynamic changes and cytokine responses in a rat model of
      hemorrhagic shock. METHODS: Wistar male rats (n=40; 8/group) were subjected to a
      volume-controlled hemorrhagic shock for 30 minutes and received lactated Ringer's
      solution resuscitation as follows: (1) immediate resuscitation, (2) delayed
      resuscitation begun 30 minutes after hemorrhage (delayed resuscitation 30), (3)
      delayed resuscitation begun 45 minutes after hemorrhage (delayed resuscitation
      45), (4) delayed resuscitation begun 60 minutes after hemorrhage (delayed
      resuscitation 60), or (5) unresuscitated group, induction of hemorrhagic shock
      without resuscitation. Hemodynamic parameters were recorded and blood samples
      were collected at 0 minutes and at 30, 90, 150, 210, 270, and 330 minutes after
      hemorrhage for plasma levels of interleukin (IL) 6, IL-10 and tumor necrosis
      factor alpha (TNF-alpha). Repeated-measurement analysis of variance was used for
      within- and between-groups comparisons. RESULTS: Final mean blood pressure, serum
      levels of lactate, and hematocrit levels after immediate resuscitation were not
      different from those in the delayed resuscitation groups. Comparing with the
      unresuscitated group, TNF-alpha and IL-6 concentrations were significantly
      higher, whereas IL-10 concentrations were significantly lower in the 4
      resuscitation groups. Circulating concentrations of IL-6 were significantly
      higher in the delayed resuscitation 45 (P<.001) and delayed resuscitation 60
      (P<.001) groups. Circulating concentrations of TNF-alpha and IL-10 in the 4
      resuscitation groups were comparable throughout the experimental period.
      CONCLUSION: Delayed fluid resuscitation in hemorrhagic shock induces increased
      production of proinflammatory cytokines, and the release of cytokine was
      correlated with the time delayed for resuscitation.

PMID- 17011073
TI  - Variability in out-of-hospital trauma care: so what?

PMID- 17011074
TI  - Spanish and English video-assisted informed consent for intravenous contrast
      administration in the emergency department: a randomized controlled trial.
AB  - STUDY OBJECTIVE: This study determined whether Spanish and English educational
      videos are superior to routine discussion for informing emergency department (ED)
      patients about risks, benefits, and alternatives to receiving intravenous
      contrast for computed tomography (CT). METHODS: A prospective randomized
      controlled trial was performed on a convenience sample of adult ED patients
      scheduled to receive intravenous contrast for CT. Patients randomized to the
      intervention group watched a video in Spanish or English explaining the procedure
      and its risks, benefits, and alternatives. The control group underwent routine
      discussion, receiving intravenous contrast information from their emergency
      physician. After their educational sessions, all participants completed a 10
      question intravenous contrast knowledge measure and 1 question rating
      satisfaction with the informed consent process. Mean scores were compared to
      assess whether the videos were superior to routine discussion for educating
      patients about intravenous contrast. Secondary outcomes included the proportion
      of satisfied patients and refusals to sign consent. RESULTS: Of the 112 patients
      enrolled, 56 were randomized to the video group and 56 to routine discussion.
      Five patients withdrew from the study, leaving 107 for analysis (video N=53;
      control N=54). Mean knowledge scores were higher in the video group (68.1%)
      compared to routine discussion (47.8%) (95% confidence interval [CI] for the
      difference 12.6% to 28.1%). Video-group patients exhibited greater satisfaction
      than routine-discussion patients (86.8% [95% CI 74.6% to 94.5%] versus 77.4% [95%
      CI 63.8% to 87.7%]). All patients signed consent to receive intravenous contrast.
      CONCLUSION: Using Spanish and English educational videos yielded higher
      intravenous contrast knowledge scores compared with routine informed consent
      procedures.

PMID- 17011075
TI  - Implementation and evaluation of a training program for the management of sexual
      assault in the emergency department.
AB  - STUDY OBJECTIVE: Sexual assault nurse examiner (SANE) programs have improved the
      quality of care for sexual assault victims. An adverse effect of these programs
      is reduced resident clinical exposure to victims of sexual assault. The
      objectives of this project are to determine the baseline level of resident
      competence in knowledge and management of sexual assault and to demonstrate the
      effectiveness of training in developing resident competence. METHODS: The study
      included 27 emergency medicine residents at an urban academic center with an
      active SANE program. The design included pretest, intervention, and retest at 6
      months. The intervention included 8 hours of lecture, role play, and skills
      laboratories. Objectives were based on SANE standards. The 4 assessments were a
      written knowledge test, evidence collection on mannequin, standardized patient
      interviews, and a written emergency department note. Data were compared with
      paired t tests. RESULTS: Twenty-three (85%) residents completed the study.
      Preintervention, residents scored 56% on the written knowledge test, 63% on
      evidence collection, 71% on standardized patient interviews, and 66% on the
      written note. Residents showed significant postintervention improvements in
      written knowledge (improvement 24%; 95% confidence interval [CI] 20% to 27%) and
      evidence collection (improvement 18%; 95% CI 12% to 24%). Performance on
      standardized patient-based communication skills did not change after the
      intervention. Resident posttest scores were similar to those of SANE providers.
      CONCLUSION: Emergency medicine residents training in an urban center with an
      active SANE program had limited knowledge and skills in the treatment of victims
      of sexual assault. Our multimodal educational intervention increased residents'
      knowledge and evidence collection skills to levels equivalent to that of
      experienced providers in a SANE program.

PMID- 17011076
TI  - The production of antibodies that distinguish rat choline acetyltransferase from
      its splice variant product of a peripheral type.
AB  - To produce antibodies that permit the immunohistochemical discrimination of
      choline acetyltransferase of the common type (cChAT) from its splice variant of a
      peripheral type (pChAT), we immunized rabbits with a cChAT specific recombinant
      protein encoded by ChAT exons 7 and 8 of the rat cChAT gene. Successful antibody
      production was proved by Western blotting on rat brain and on HEK293 cells
      expressing green fluorescent protein (GFP), cChAT-GFP and pChAT-GFP. By
      immunohistochemistry our antiserum clearly labeled known cholinergic structures
      in rat brain, but gave no positive staining in the trigeminal ganglion which
      contained many neurons positive with pChAT antiserum.

PMID- 17011077
TI  - Blood inflammatory markers and risk of dementia: The Conselice Study of Brain
      Aging.
AB  - Incidence studies of blood inflammatory markers as predictors of dementia in
      older age are few and did not take into account hyperhomocysteinemia, although
      this condition is associated with both inflammation and increased risk of
      dementia. We investigated the relationships of baseline serum C-reactive protein
      (CRP), serum interleukin 6 (IL6), plasma alpha-1-antichymotrypsin, and
      hyperhomocysteinemia (defined as plasma total homocysteine>15 micromol/L) with
      risk of incident Alzheimer's disease (AD) and vascular dementia (VaD) in a
      dementia-free Italian population-based elderly cohort (n=804, 53.2% women, mean
      age 74 years) with 4 years of follow-up. No inflammatory marker, alone or in
      combination, predicted AD risk whereas the combination of high CRP and high IL6
      was associated with risk of VaD (HR, 2.56; 95%CI, 1.21-5.50) independently of
      socio-demographic confounders, traditional risk factors and hyperhomocysteinemia.
      By contrast, in the same model, hyperhomocysteinemia was independently associated
      with AD (HR, 1.91; 95%CI, 1.02-3.56) but not VaD risk. Blood inflammatory markers
      are associated with increased VaD risk but do not predict AD, which seems
      selectively associated with hyperhomocysteinemia.

PMID- 17011078
TI  - Leptin gene transfer in the hypothalamus enhances longevity in adult monogenic
      mutant mice in the absence of circulating leptin.
AB  - Leptin, a product of the ob gene, is a pleiotropic signal implicated in
      regulation of multiple physiological functions in the periphery and centrally,
      including hypothalamic integration of energy homeostasis. Recessive mutations of
      ob gene result in early onset of hyperphagia, morbid obesity, metabolic
      disorders, early mortality and shortened life-span. Intracerebroventricular
      injection of recombinant adeno-associated virus vector (rAAV) encoding the leptin
      gene in adult obese ob/ob mice enhanced leptin transgene expression only in the
      hypothalamus, normalized food intake, body weight and more than doubled the life
      span as compared to control cohorts and extended it to near that of normal wild
      type mice. These life-extending benefits were associated with drastic reductions
      in visceral fat, and blood glucose and insulin levels, but elevated ghrelin
      levels, the anti-aging biomarkers. Thus, bioavailability of leptin transduced by
      ectopic gene in the hypothalamus alone is both necessary and sufficient to
      normalize life-span. Evidently, site-specific ectopic gene expression with rAAV
      is durable and safe for alleviating neural disorders that stem from missing or
      functional disruption of a single gene.

PMID- 17011079
TI  - Azithromycin-sulfonamide conjugates as inhibitors of resistant Streptococcus
      pyogenes strains.
AB  - Novel hybrid compounds 6a-6d, conjugates of 15-membered azalides and
      sulfonamides, i.e. unsubstituted, 4-aryl- and 4-heteroaryl-aminosulfonyl
      derivatives of 9a-[N'-(phenylcarbamoyl)]-9-deoxo-9-dihydro-9a-aza-9a
      homoerythromycin A were synthesized and characterized by IR, one- and two
      dimensional NMR spectroscopies and MALDI-TOF and MS/MS mass spectrometry. The new
      compounds were evaluated in vitro against a panel of sensitive and resistant Gram
      positive and Gram-negative bacterial strains. 9a-{N'-[4
      (Aminosulfonyl)phenyl]carbamoyl}--(6a) and 9a-{N'-[4
      (phenylaminosulfonyl)phenyl]carbamoyl}--(6b) derivatives showed improvements in
      activity against inducible resistant Streptococcus pyogenes in comparison with
      macrolide antibiotic azithromycin and starting material 9-deoxo-9-dihydro-9a-aza
      9a-homoerythromycin A (2). In addition, the synthesized azithromycin-sulfonamide
      conjugates 6a-6d showed good antibacterial activity against sensitive S. pyogenes
      and Streptococcus pneumoniae strains. The kinetics of degradation in the
      artificial gastric juice showed that the most active compounds, 6a and 6b,
      exhibited azithromycin like stability. The cleavage of the cladinose sugar was
      found to be the main decomposition pathway leading to inactive 7a and 7b,
      prepared also as analytical standards by the alternative synthetic route together
      with 7c and 7d.

PMID- 17011080
TI  - Design and synthesis of anticonvulsants from a combined phthalimide-GABA-anilide
      and hydrazone pharmacophore.
AB  - Two series of pharmacophoric hybrids of phthalimide-GABA-anilides/hydrazones were
      designed and synthesized and evaluated for their anticonvulsant and neurotoxic
      properties. The structures of the synthesized compounds were confirmed by the use
      of their spectral data besides elemental analysis. Initial anticonvulsant
      screening was performed using intraperitoneal (i.p.) maximal electroshock-induced
      seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine
      (scSTY), and intraperitoneal picrotoxin (ipPIC)-induced seizure threshold tests.
      All of the compounds were ineffective in the MES test. Most of the compounds were
      found to be effective in the scSTY and ipPIC models and very few compounds showed
      protection in the scPTZ model.

PMID- 17011081
TI  - [Economic evaluation of at home subcutaneous and intravenous immunoglobulin
      substitution].
AB  - BACKGROUND: Intravenous (IV) and subcutaneous (SC) immunoglobulin (Ig)
      administration is a safe and an efficacious treatment in patients with IgG
      deficiency. Home administration of IV Ig and SC Ig has recently been approved in
      France. Most of the patients treated in hospital ask for home treatment. Some
      patients prefer monthly IV administration, others weekly SC administration.
      MATERIAL AND METHODS: We evaluated in details the cost of both of these
      practices. We currently use electric pumps for both IV and SC administration
      which are fixed to the patient giving complete freedom and mobility. RESULTS: For
      20 g administrated per 4 week, the total cost of home treatment is 1,518 euro
      with SC Ig and 1,033 euro with IV Ig. For 40 g administrated per 4 week, the
      total cost of home treatment is 2,507 euro to 2,729 euro with SC Ig and 2,034
      euro with IV Ig. The difference is mainly explained by the cost of renting the
      electric pumps and by the cost of furniture for SC administration. The choice of
      home Ig substitution must be given to all patient receiving treatment in
      hospital. CONCLUSIONS: Home IV and home SC perfusions are two possible options
      each different with there own advantages and disadvantages. The cost of each
      procedure must be known by the medical staff.

PMID- 17011082
TI  - Designing quality course management systems that foster intra-professional
      education.
AB  - This paper draws on the experiences of the author in designing and implementing
      quality course management policies and procedures for vocational and higher
      educational programs, both overseas and in Australia. In particular, the paper
      focuses on those programs of study that require practicums within the curriculum.
      Whether these are clinical nursing placements, physiotherapy hands-on practical
      blocks or teacher training instruction, there are many principles of adult
      education that can be applied to the design and development of course management
      systems that foster inter-professional education. It is important that the
      components of any such system allow for a multi-faceted approach that relates
      collaborative learning to collaborative practice and supports a team of
      professionals through the skilled use of group-based learning, interactive
      assessments and inter-organisational processes and practices. The term 'course
      management system' is used here to describe all those policies and procedures
      that form the framework of any higher education department or faculty that has
      the overall responsibility for developing curriculum, teaching and learning
      resources that ensure quality educational outcomes for its students. In these
      days of multi-skilling, the benefits of inter-professional education may be
      significant. To guarantee that standards are kept high and learning outcomes are
      achievable, the management of an educational system must cover many areas of
      professional practice. It needs to be supported by all stakeholders in the
      organisation so that there is an environment of understanding, good interpersonal
      communication, supportive inter-group relations and an atmosphere of
      professionalism that is pervasive. This paper introduces a third definition to
      the model and suggests that intra-professional education be added to form a
      tripartite foundation for quality professional learning outcomes.

PMID- 17011083
TI  - The use of pre- pro- and synbiotics in adult intensive care unit patients:
      systematic review.
AB  - BACKGROUND & AIMS: This review investigated whether the administration of enteral
      pre-, pro- and synbiotics compared with controls in adult intensive care unit
      (ICU) patients reduced the incidence of nosocomial infections, length of ICU
      stay, hospital mortality and specifically pneumonia. METHODS: Systematic review
      of randomised controlled trials comparing enteral feeding and pre-, pro- or
      synbiotics, versus standard enteral feed alone, in patients admitted to adult
      ICUs. RESULTS: Eight randomised studies with a total of 999 critically ill adult
      patients met the inclusion criteria. Pre- pro- or synbiotics were not associated
      with any significant change in the outcomes studied-length of ICU stay, hospital
      mortality and the incidence of nosocomial infection and more specifically
      pneumonia incidence. Few data were available for other outcomes. CONCLUSIONS: The
      use of pre- pro- or synbiotics in adult critically ill patients confers no
      statistically significant benefit in the outcome criteria studied. There is
      currently a lack of evidence to support the use of pre- pro- or synbiotics in
      patients admitted to adult ICUs, and a large well-designed trial is needed in
      this area.

PMID- 17011084
TI  - Influenza vaccination coverage among hospital personnel over three consecutive
      vaccination campaigns (2001-2002 to 2003-2004).
AB  - This study was carried out to assess influenza vaccination coverage among
      hospital personnel and the impact of health promotion campaigns, within the
      hospital, designed to increase vaccination coverage over three consecutive
      vaccination campaigns (2001-2002 to 2003-2004). The health promotion tool used in
      the 2001-2002 and 2002-2003 were informative posters distributed throughout the
      hospital. In the 2003-2004 season, the recommendation was also published in the
      internal bulletin and Web site of the hospital. In addition, a physician and a
      nurse from the Department of Preventive Medicine visited all departments offering
      vaccination in the work place. The overall vaccination coverage in the 2001-2002
      campaign was 16% with coverage of 11.5% in nurses and 15% in physicians. In the
      2002-2003 and 2003-2004 campaigns the overall vaccination coverage was 21% and
      40%, respectively (p<0.01). Staff physicians and resident physicians reached 60
      and 42% coverage rates in the 2003-2004 campaign, but coverage in nurses and
      nursing assistant remained around 30% (p<0.01). In summary, influenza vaccination
      coverage among hospital based healthcare personnel increased significantly during
      the last three seasons, however, it still remains low despite active attempts at
      promoting influenza vaccination.

PMID- 17011085
TI  - Brief review of the clinical effectiveness of PREVENAR against otitis media.
AB  - Pre-licensure trials in Finnish and US infants demonstrated that PREVENAR was
      associated, respectively, with a 6% (95% CI, -4% to 16%) and an 8.9% (95% CI, 5.8
      11.8%) overall reduction in clinical AOM incidence. Long-term follow-up of these
      cohorts revealed that there was an approximately 10-50% vaccine efficacy against
      recurrent otitis media or for the prevention of tympanostomy tube placement. In
      surveillance reports from the USA that followed infants with serious AOM,
      generalized PREVENAR vaccination led to an important fall in the incidence of
      pneumococcal otitis media, particularly for cases that would have been frequent
      or would have been refractory to antibiotic treatment. The rate of pneumococcal
      MEF isolates fell by 39% for severe otitis media [McEllistrem MC, Adams JM, Patel
      K, Mendelsohn AB, Kaplan SL, Bradley JS, et al. Acute otitis media due to
      penicillin-nonsusceptible Streptococcus pneumoniae before and after the
      introduction of the pneumococcal conjugate vaccine. Clin Infect Dis
      2005;40(12):1738-44], by 42%, among persistent or treatment-resistant otitis
      media [Casey JR, Pichichero ME, Changes in frequency and pathogens causing acute
      otitis media in 1995-2003. Pediatr Infect Dis J 2004;23(9):824-8 [see comment]]
      and by 66% among severe otitis media cases or from 'otitis-prone' children [Block
      SL, Hedrick J, Harrison CJ, Tyler R, Smith A, Findlay R, et al. Community-wide
      vaccination with the heptavalent pneumococcal conjugate significantly alters the
      microbiology of acute otitis media. Pediatr Infect Dis J 2004;23(9):829-33 [see
      comment]].

PMID- 17011086
TI  - Effect of allergen-specific immunotherapy on platelet secretory activity in
      patients with grass-pollen allergy.
AB  - Platelet may become activated following antigen challenge to participate then
      actively in the immune-inflammatory response. Moreover, some evidence proves that
      specific immunotherapy induces changes in the platelet function. The objective of
      this study was to determine circulating platelet activity during the early phase
      of allergen-specific immunotherapy (SIT) in patients with grass pollen-sensitive
      allergic rhinitis. Twelve grass-pollen allergic patients (seven men and five
      women) with intermittent allergic rhinitis were treated with specific
      subcutaneous allergoid preparation. SIT was received by six weekly injections,
      the vaccine dose increasing until the maintenance level was reached. Blood was
      sampled at four different time points: before and directly before SIT, 30 min and
      24 h after the maximum dose injection of the vaccine. Plasma level of beta
      thromboglobulin (beta-TG), marker of platelet activation in vivo was measured
      using ELISA method. Baseline beta-TG level did not differ significantly among the
      patients and healthy subjects. Moreover, no significant differences were observed
      in the degree of platelet activity between the different times of this study in
      the patients group. We failed to detect any significant changes in circulating
      platelet activity, the measure of plasma level of beta-TG, in patients with grass
      pollen induced intermittent rhinitis during the course of the dose increase phase
      of grass pollen SIT. In particular, it seems that both early (after 30 min) and
      late (after 24 h) changes in plasma level of this marker do not occur following
      the maximum dose administration of the allergen vaccine during the early SIT
      phase.

PMID- 17011087
TI  - Lectin-affinity chromatography for downstream processing of MDCK cell culture
      derived human influenza A viruses.
AB  - The presented study aims on the development of a capture step for the
      purification of cell culture derived influenza viruses using lectin affinity
      chromatography. Human influenza A/Puerto Rico/8/34 virus produced in Madin Darby
      canine kidney cells have been chosen as a model. The influenza A virus envelop
      possesses two viral glycoproteins: hemagglutinin and neuraminidase.
      Oligosaccharides of theses glycoproteins can be targeted as affinity ligands
      using specific lectins. First, lectins have been screened via lectin blots and
      spin columns. Adequate lectins have been chosen based on published glycan
      structures of hemagglutinin. The most specific binding was achieved via the
      galactose specific Erythrina cristagalli and Euonymus europaeus lectins. Second,
      the chromatographic separations characteristics of these lectins have been
      further determined via FPLC. These experiments revealed that the rate of
      hemagglutinin glycan binding to the ligands was higher with the E. europaeus
      compared to the E. cristagalli lectin. Third, viral recoveries in addition to the
      total protein and host cell DNA have been balanced in a series of E. europaeus
      lectin chromatography runs. The total protein and dsDNA content in the product
      fraction of the affinity chromatography was reduced from the starting conditions
      to 21% and 0.1%, respectively. The average viral recovery in the product fraction
      was 97%. SDS-PAGE analysis indicated that the majority of the eluted proteins
      were of viral origin. The reproducibility and column stability was confirmed in
      up to 25 runs applying six different virus product batches.

PMID- 17011088
TI  - Information, knowledge and expectations of the routine ultrasound scan.
AB  - OBJECTIVE: To examine the current provision of pre-ultrasound information to
      women; to determine if the information provided was related to women's knowledge
      of the routine second trimester ultrasound; and to describe women's expectations
      of the scan. DESIGN: A descriptive survey, before and after design. SETTING:
      Tertiary referral centre in the Republic of Ireland. PARTICIPANTS: A convenience
      sample of pregnant women attending for routine second trimester ultrasound scan.
      MEASUREMENTS: Self-report questionnaires were used to explore the availability of
      information about the test, the extent of women's knowledge and expectations of
      the examination, and the degree to which expectations were achieved. FINDINGS:
      Most women received little information from health professionals about the
      capability and limitations of the scan, and had expectations that exceeded the
      purpose and ability of the examination. Most women, however, stated that their
      expectations were met in most cases. Although the routine ultrasound in the study
      site is not a targeted fetal anatomical survey, most women were concerned with
      this aspect of the test. KEY CONCLUSIONS: If women are to have realistic
      expectations of the routine ultrasound scan, then improvements are required in
      the provision of pre-ultrasound information, particularly in relation to the
      technological limitations of the examination. Consideration should be given to
      the context of the high appeal associated with visualising the fetus for women
      when unachievable expectations are reported as having been met. IMPLICATIONS FOR
      PRACTICE: Any development of prenatal screening programmes that will uncover
      fetal abnormalities needs to be considered in context, in particular when
      termination of pregnancy is not available within the jurisdiction. Women had
      expectations of the examination that could not, because of technological
      limitations, have been met by the examination, but which they perceived to have
      been met. Knowledge of the purpose, capabilities and limitations of the routine
      second trimester ultrasound scan was not influenced by the mode of information
      provision.

PMID- 17011089
TI  - The anatomical site of constriction of the median nerve in patients with severe
      idiopathic carpal tunnel syndrome.
AB  - During open carpal tunnel release in patients with severe idiopathic carpal
      tunnel syndrome, an area of constriction in the substance of the median nerve is
      frequently noted. In a prospective study of 30 patients, the central point of the
      constricted part of the nerve was determined intraoperatively and found to be, on
      average, 2.5 (range 2.2-2.8)cm from the distal wrist crease. This point always
      corresponded to the location of the hook of the hamate bone. These intraoperative
      findings were compared with the "narrowest" point of the carpal canal as
      determined by anatomical and radiological studies in the literature.

PMID- 17011090
TI  - Cerclage-wiring-assisted fixation of difficult hand fractures.
AB  - Difficult hand fractures with multiple butterfly fragments, multiple cortical
      splits or intraarticular extension continue to pose a challenge for optimal
      stable fixation that allows early postoperative mobilisation. In this study, we
      describe the use of cerclage-wire-assisted fixation of 17 difficult hand
      fractures in 16 patients. The cerclage wires helped to maintain the reduction, so
      providing sufficient initial stability for placement of a plate and screws.
      Stable fixation of the fracture was then accomplished without losing the
      reduction. One to three cerclages of stainless-steel wires were used for the
      preliminary fixation. Stable fixation was then accomplished by a bridging or
      neutralising plate technique. Postoperatively, the fixation was sufficiently
      stable to allow immediate mobilisation. With an average follow up of 44.5 months,
      all 17 fractures united without loss of reduction. At final follow-up, the
      average total active range of motion was 247 degrees (range 220-260 degrees ).

PMID- 17011091
TI  - Growth of Lygeum spartum in acid mine tailings: response of plants developed from
      seedlings, rhizomes and at field conditions.
AB  - Lygeum spartum is a native species in semiarid Mediterranean areas that grows
      spontaneously on acid mine tailings. We aimed to study the suitability of this
      plant for phytostabilization. L. spartum was grown from both seeds and rhizomes
      in acid mine tailings with various fertilizer and lime treatments. Untreated
      soils had a solution pH of 2.9 with high concentrations of dissolved salts
      (Electrical Conductivity 25 dS m(-1)) and Zn (3100 mg L(-1)). Plants grown on
      untreated soil had high shoot metal concentrations (>4000 mg kg(-1)Zn). Liming
      increased the solution pH to 5.5 and reduced the dissolved salts by more than
      75%, resulting in lower shoot metal accumulation. Plants grown from rhizomes
      accumulated less metal than those grown from seeds. Plants collected in the field
      had metal concentrations an order of magnitude less than plants raised in the
      growth chamber. These differences may be due to the higher moisture content and
      homogeneous nature of the soils used in the pot experiment.

PMID- 17011092
TI  - Determination of selected quaternary ammonium compounds by liquid chromatography
      with mass spectrometry. Part II. Application to sediment and sludge samples in
      Austria.
AB  - Soxhlet extraction and high-performance liquid chromatography (HPLC) coupled to
      tandem mass spectrometry detection (MS/MS) was used for the determination of
      selected quaternary ammonium compounds (QACs) in solid samples. The method was
      applied for the determination of alkyl benzyl, dialkyl and trialkyl quaternary
      ammonium compounds in sediment and sludge samples in Austria. The overall method
      quantification limits range from 0.6 to 3 microg/kg for sediments and from 2 to 5
      microg/kg for sewage sludges. Mean recoveries between 67% and 95% are achieved.
      In general sediments were especially contaminated by C12 chain benzalkonium
      chloride (BAC-C12) as well as by the long C-chain dialkyldimethylammonium
      chloride (DDAC-C18) with a maximum concentration of 3.6 mg/kg and 2.1mg/kg,
      respectively. Maxima of 27 mg/kg for DDAC-C10, 25 mg/kg for BAC-C12 and 23 mg/kg
      for BAC-C14 were determined for sludge samples. The sums of the 12 selected
      target compounds range from 22 mg/kg to 103 mg/kg in the sludge samples.

PMID- 17011093
TI  - Irreconcilable differences: health professionals' constructions of adolescence
      and motherhood.
AB  - Adolescent motherhood has been associated with negative health outcomes for both
      adolescent mothers and their children in many studies. Although the link between
      early motherhood and disadvantage has more recently been questioned, professional
      understandings continue to focus on hardship and social exclusion. Social
      constructionism provides a critical approach to the professional constructions of
      adolescent motherhood. Using discourse analysis, transcripts of individual
      interviews with 17 New Zealand health professionals working in a variety of
      settings were analysed to examine the discourses used to construct adolescent
      motherhood. During the interviews, doctors, midwives, and nurses drew upon
      'Developmental' and 'Motherhood' discourses to position adolescent mothers as
      problematic. The 'Developmental' discourse positions young mothers as
      'adolescents' who are naive, distracted, and self-centred, and hence unable to
      mother correctly. The health professionals also employed a 'Motherhood' discourse
      that attributes certain behaviours to 'good' mothers. These discourses were drawn
      upon to illustrate how the characteristics of an 'adolescent' cannot be
      reconciled with the attributes of a 'good' mother. These constructions have
      implications for health care provision for adolescent mothers in New Zealand.

PMID- 17011094
TI  - Hope and hoping in the talk of dying cancer patients.
AB  - Hope is the subject of increasing research and discussion within the healthcare
      literature. However, although deemed of vital import to patient welfare, there is
      little examination of how hope features within patients' speech. This qualitative
      study presents the discursive properties of hope as it emerged unprompted during
      semi-structured interviews with 28 patients in the final phase of terminal cancer
      recruited from the oncology clinic of the Royal Adelaide Hospital, Australia. In
      the context of discussions about decision-making at the end of a terminal
      illness, when used as a noun, hope invariably referenced the medical domain-
      focussing either on the objective probability of medical cure (typically taking
      the negative form "there is no hope"), or the subjective possession of the
      patient, needed to fight their disease. Positioning the patient as relatively
      powerless and subject to external forces, this hope was most commonly associated
      with absolute solutions, and life-and-death stakes. Hope as a verb emphasised the
      patient's active engagement in life, identifying what was good and positive for
      them. It was used to assign responsibility to others, to indicate and establish
      solidarity or agreement between the speaker and others, effectively strengthening
      interpersonal ties between individuals. Through hoping, patients established
      connection with others and with the future. In the context of interactions
      between patients and clinical staff, we conclude that the use of hope-as-a-verb
      may have benefits, enabling the patient--even when dying--to focus on the
      positive, to connect to others, and to continue to engage with life.

PMID- 17011095
TI  - Daily negative interactions and mood among patients and partners dealing with
      multiple sclerosis (MS): the moderating effects of emotional support.
AB  - Negative interactions with intimate partners may have adverse consequences for
      well-being, especially for individuals dealing with chronic illness. However, it
      is not clear whether negative interactions affect both dimensions of positive and
      negative well-being and factors that may moderate this effect have not been well
      described. The aim of the present study was to examine the association between
      daily received negative responses from the partner and end-of-day positive and
      negative mood in patients with multiple sclerosis (MS) and their intimate
      partners. Further, the moderating role of receiving emotional support from the
      partner on the same day was examined. Sixty-one MS patients and their intimate
      partners were approached via one MS centre and the neurology department of one
      hospital in the Netherlands and completed computerized diaries for 14 days. Both
      partners filled out diaries at the end of each day, recording received negative
      responses, emotional support and end-of-day positive and negative mood. In line
      with a domain specific model, patients or partners who reported receiving
      negative responses on a day had higher end-of-day negative mood, whereas received
      negative responses were unrelated to end-of-day positive mood. Further, for both
      patients and partners, the adverse effect of received negative responses on end
      of day mood was moderated by receiving emotional support on the same day.

PMID- 17011096
TI  - Prefrontal but not temporal grey matter changes in males with first-episode
      schizophrenia.
AB  - INTRODUCTION: Changes of brain morphology are now considered as a part of the
      pathology of schizophrenia. Voxel-based morphometry may be used to study regional
      changes of the grey matter in the whole brain. It is advantageous to study first
      episode patients to prevent the influence of many possible biasing factors when
      trying to identify primary pathological processes underlying the manifestation of
      the illness. OBJECTIVE: To investigate regional grey matter changes in the first
      episode schizophrenia patients. METHODS: Optimized voxel-based morphometry was
      used to detect changes in grey matter volume in 22 patients with first-episode
      schizophrenia compared with 18 healthy volunteers of comparable age, gender and
      handedness. RESULTS: The first-episode schizophrenia group had significantly
      reduced grey matter volume in the prefrontal cortex (inferior and middle
      prefrontal gyrus, cingulate gyrus). We identified no differences in the temporal
      cortex. CONCLUSION: Our data support the theoretical assumption that prefrontal
      dysfunction underlines the primary pathology and clinical manifestation of
      schizophrenia. We are inclined to explain the differences in the pattern of
      morphological changes reported in other first-episode studies--especially the
      lack of changes in the temporal cortex--by heterogeneity of schizophrenia,
      potential progression and antipsychotic medication effect.

PMID- 17011097
TI  - Suppression of verbal hallucinations and changes in regional cerebral blood flow
      after intravenous lidocaine: a case report.
AB  - Simple and complex auditory phantom-perceptions such as tinnitus and musical
      hallucinations occur predominantly in elderly subjects and are often associated
      with hearing impairment. Isolated verbal hallucinations without other psychotic
      features are rare. It has been shown that an intravenous (i.v.) injection of
      lidocaine can transiently suppress tinnitus. Here we present the case of a 74
      year old left-handed women with severely distressing, continuous verbal auditory
      hallucinations without other psychotic features. I.v. injections of 100 mg
      lidocaine but not saline resulted in substantial transient suppressions of the
      hallucinations for several hours. Using [(15)O]H(2)O positron-emission tomography
      (PET) decreased regional cerebral blood flow associated with reduced perception
      of voices was found in the right angular and supramarginal gyrus, right inferior
      frontal gyrus, orbitofronal cortex and in major parts of the cingulate cortex.
      These data suggest to further investigate the clinical relevance of i.v.
      lidocaine in patients with therapy-resistant verbal hallucinations, support the
      notion of common pathophysiological mechanisms in different forms of auditory
      phantom-perception and demonstrate the feasibility of a new strategy for imaging
      studies on auditory hallucinations.

PMID- 17011098
TI  - Baroreflex mechanisms in major depression.
AB  - BACKGROUND: Recent studies have shown that depressive disorder is associated with
      impaired baroreceptor or baroreflex sensitivity, which is proposed to be a
      predisposing factor for sudden death in patients with manifest cardiac disease.
      These studies have not evaluated the afferent and efferent components of the
      cardiac baroreflex loop or other baroreflex mechanisms that regulate target
      processes (cardiac metabolism and blood pressure variability) related to the
      impairment. The objective of this study was to gain more insight into autonomic
      functioning in depressive disorder to more fully examine the potential basis for
      increased cardiac mortality. METHODS: The subjects were 28 women and men with
      unipolar major depression who were taking antidepressant medications and who were
      in partial remission and free of cardiovascular or other serious disease, and 28
      healthy control subjects matched for sex, age, and ethnicity. The two samples
      were compared for negative affective dispositions (anger expression, hostility,
      defensiveness, anxiety), spontaneous (closed-loop) baroreflex activity, heart
      rate, heart rate variability, systolic blood pressure, and heart rate-systolic
      blood pressure double product under resting conditions. RESULTS: Depressed
      patients showed a general disposition to anger suppression coupled with higher
      hostility and anxiety, and lower defensiveness. The patients showed higher
      general sympathetic activity (high levels of blood pressure, low-frequency heart
      rate variability) and lower parasympathetic-related activity (high heart rate and
      reduced high frequency heart rate variability) with affected cardiac metabolism
      estimated by the double product. Depressed patients had lower baroreflex
      sensitivity related to a higher gain of the afferent component of the baroreflex
      without respective gain adjustment of its efferent component (reflex gain 'de
      afferentation'). It was coupled with a compensatory higher number of effective
      baroreflex reactions (reflex gating 're-afferentation'). Antidepressant agents
      and depressed mood had additional independent effects on baroreflex sensitivity
      through the efferent component of the cardiac baroreflex loop. CONCLUSIONS: The
      data indicate that different baroreflex components and mechanisms may be impaired
      in patients with depression and may contribute to their increased cardiac risk.

PMID- 17011099
TI  - Risk assessment of triclosan [Irgasan] in human breast milk.
AB  - Triclosan is an established bacteriostatic compound widely used in topical and
      dental preparations. Its pharmacokinetics and toxicology have been extensively
      studied in humans and animals. It is known to be absorbed from the
      gastrointestinal tract and across the skin. A recent report noted its occurrence
      in human breast milk and this has now been further investigated. Sixty two
      unselected samples of human milk from Breast Milk Banks in California and Texas
      have been analysed for triclosan; the concentration ranged from 0 to 2100
      microg/kg lipid. A risk assessment of triclosan in human milk has been made,
      based on a conservative calculation of exposure of neonates and experimental
      toxicity test results. The broad set of reproduction toxicity tests of triclosan
      includes a 2-generation study in the rat, in which there was considerable
      exposure of dams and pups to triclosan throughout fetal development and up to
      sexual maturity in the F2 generation, and a further study in which pups of dosed
      dams were followed to weaning. They established an oral NOAEL for pups of 50
      mg/kg/d. The maximum exposure of babies via breast milk calculated using very
      conservative additive assumptions is approximately 7.4 microg/kg/d. The 'Margin
      of Exposure' between the NOAEL and that calculated in breast fed babies is
      approximately 6760-fold. It is concluded that there is no evidence to indicate
      that the presence of a miniscule amount of triclosan in breast milk presents a
      risk to babies.

PMID- 17011100
TI  - Subchronic 90-day oral (Gavage) toxicity study of a Luo Han Guo mogroside extract
      in dogs.
AB  - A combined 28-day and 90-day oral (Gavage) study was conducted in male and female
      dogs to investigate the safety of PureLo, a non-caloric sweetener derived from
      the Chinese fruit Luo Han Guo, which achieves its sweetness from the presence of
      triterpene glycosides known as mogrosides. Three dogs of each sex were
      administered 10 mL/kg bw/day of either an aqueous solution providing 3000 mg/kg
      bw/day of PureLo or distilled water for either 28 days or 90 days. Measurements
      included clinical observations, body weight, food consumption, hematology, blood
      chemistry, urinalysis, gross necropsy, organ weight, and histopathology. There
      were no significant adverse effects on any of these measures. Based on the lack
      of toxicological effects in the study, the NOAEL for PureLo is 3000 mg/kg bw/day
      when administered to dogs by Gavage for 90 consecutive days.

PMID- 17011101
TI  - The effect of short-term lyophilized beer consumption on established hypertension
      in rats.
AB  - Effects of short-term lyophilized beer (LB) consumption on normotensive (WKY) and
      hypertensive (SHR) rats are reported. It was found that LB contains high
      quantities of bioactive compounds and has a high antioxidant potential. The WKY
      and SHR rats were divided into four groups of 8, two experimental and two
      controls, which were named LBWKY and LBSHR and ControlWKY and ControlSHR,
      respectively. LB was given to the rats of the LBWKY and LBSHR groups
      intragastrically at a dose of 2.72 g/kg in a volume of 10 ml/kg for 10 days. The
      rats of the control groups received saline solution. The following indices were
      determined: body weight gain, heart rate, systolic blood pressure, using a tail
      cuff method and GABA accumulation in the hypothalamus and the pons-medulla as
      measured by GABA-T inhibition. It was found that the treatment of rats with LB
      had no effect on the blood pressure and heart rate values. In both rat strains,
      LB decreased GABA accumulation in the hypothalamus and the pons-medulla. A
      significant reduction of body weight gain was observed in both LB-treated groups
      when compared with the corresponding controls. In conclusion, LB contains high
      quantities of bioactive compounds and possesses a high antioxidant potential.
      Diet supplemented with LB causes significant reduction of the central GABAergic
      activity in WKY and SHR rats without any effect on cardiovascular function. In
      addition, in both animal strains there was an apparent inverse association
      between LB intake and body weight gains.

PMID- 17011102
TI  - Sub-chronic (13-week) oral toxicity study with D-ribose in Wistar rats.
AB  - The present study evaluated the toxicity from sub-chronic administration of D
      ribose (DR) to male and female albino Wistar rats. Groups of 20 male and 20
      female rats were exposed via the diet to 0%, 5%, 10%, or 20% DR, seven days per
      week (mean daily intake of 0.0, 3.6, 7.6, and 15.0 g/kg body weight/day in males
      and 0.0, 4.4, 8.5, and 15.7 g/kg body weight/day in females), for 13 consecutive
      weeks. Mean feed consumption and feed conversion efficiency values were
      comparable across all study groups; however, and mean body weights of all treated
      animals were decreased relative to those of controls. Absolute cecal weights were
      increased in the mid- and high-dose animals, and the relative weights were
      increased in all treated animals. Analysis of microscopic histopathology revealed
      no evidence of changes that could be attributed to the DR treatment. It is
      scientifically reasonable to conclude that the present study supports a
      concentration of 5% DR in the diet, corresponding to an average daily intake of
      DR of 3.6 and 4.4 g/kg body weight/day in male and female rats, respectively, as
      being the absolute no observed adverse effect level (NOAEL) for this substance.

PMID- 17011103
TI  - Effect of storage, processing and cooking on glucosinolate content of Brassica
      vegetables.
AB  - Epidemiological studies have shown that consumption of Brassica vegetables
      decrease the risk of cancer. These associations are linked to dietary intake of
      glucosinolates and their metabolism to cancer preventive isothiocyanates.
      Bioavailability of glucosinolates and related isothiocyanates are influenced by
      storage and culinary processing of Brassica vegetables. In this work, the content
      of the 7 major glucosinolates in broccoli, Brussels sprouts, cauliflower and
      green cabbage and their stability under different storage and cooking conditions
      is examined. Glucosinolates and isothiocyanates were quantified by liquid
      chromatography with tandem mass spectrometric detection (LC-MS/MS).
      Isothiocyanates were detected with high sensitivity as the corresponding thiourea
      derivatives. Storage at ambient temperature and in a domestic refrigerator showed
      no significant difference and a minor loss (9-26%) of glucosinolate levels over 7
      days. Vegetables shredded finely showed a marked decline of glucosinolate level
      with post-shredding dwell time - up to 75% over 6h. Glucosinolate losses were
      detected partly as isothiocyanates. Cooking by steaming, microwaving and stir-fry
      did not produce significant loss of glucosinolates whereas boiling showed
      significant losses by leaching into cooking water. Most of the loss of the
      glucosinolates (approximately 90%) was detected in the cooking water. Increased
      bioavailability of dietary isothiocyanates may be achieved by avoiding boiling of
      vegetables.

PMID- 17011104
TI  - Cadmium, lead, and thallium in smoke particulate from counterfeit cigarettes
      compared to authentic US brands.
AB  - Smoking remains the leading cause of preventable disease in the United States.
      Exposure to tobacco smoke leads to cancer, heart and lung disease, and addiction.
      The origin of the tobacco and cigarette manufacturing practices of counterfeit
      cigarettes are unknown. Because toxic metals are incorporated into the tobacco
      lamina during cultivation, the ambient metal content of the soil could produce
      significant differences in metal levels in both the tobacco and smoke of
      counterfeit cigarettes. We compared mainstream smoke cadmium, thallium, and lead
      deliveries from counterfeit and authentic brands. Mainstream smoke levels of all
      three metals were far greater for counterfeit than the authentic brands, in some
      cases by an order of magnitude. Significant differences still existed even after
      normalizing mainstream smoke metal levels with nicotine delivery; the
      counterfeits typically delivered much higher levels of all three analytes. Our
      findings, based on 21 different counterfeit samples, suggest that counterfeit
      cigarettes potentially result in a markedly greater exposure to toxic heavy
      metals than authentic brands, even after correcting for differences in nicotine
      intake. In view of the unknown health risks associated with inhaling higher
      levels of toxic metals, it is prudent to minimize exposure to toxic substances
      whenever possible.

PMID- 17011105
TI  - Degradation of trichothecene mycotoxins by chicken intestinal microbes.
AB  - The degradation of 12 trichothecene mycotoxins by chicken intestinal microbes was
      monitored by liquid chromatography-ultraviolet-mass spectrometry under positive
      ion atmospheric pressure chemical ionization. Two pathways were observed:
      deacylation and deepoxidation. Essentially complete conversions to the deepoxy
      metabolites were observed for the non-acylated trichothecenes 4-deoxynivalenol,
      nivalenol, and verrucarol. However, deacetylation was the predominant pathway for
      the monoacetyl trichothecenes 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol
      (15ADON), and fusarenon X. Small amounts of the deepoxy metabolites were observed
      from 15ADON and large amounts from 15-monoacetoxyscirpenol where steric hindrance
      protected the C-15 acetyl groups from enzymatic attack. Diacetylated
      trichothecenes diacetoxyscirpenol and neosolaniol exhibited only deacetylation.
      The larger isovaleryl functionality was resistant to removal and deepoxidation
      was the prevalent reaction in HT-2 toxin and T-2 triol, whereas T2 toxin showed
      only deacetylation.

PMID- 17011106
TI  - Anticlastogenic activity of thymoquinone against benzo(a)pyrene in mice.
AB  - Thymoquione (TQ), the main constituent of the volatile oil of Nigella sativa
      seeds, has been shown to protect mice against benzo(a)pyrene [B(a)P]-induced
      forestomach carcinogenesis. The present investigation was undertaken to study the
      possible chemopreventive activity of TQ, supplemented in the drinking water,
      against B(a)P-induced chromosomal aberrations (CAs) in mouse bone marrow cells.
      Male Swiss albino mice received TQ (0.01% in drinking water) daily for 28 days.
      The daily dose of TQ was estimated to be 10mg/kg based on the calculated average
      daily water consumption by mice. From day 9, the carcinogen, B(a)P, was given by
      gastric intubation at dose level of 50mg/kg on alternative days for a total of 8
      doses. On day 29, all mice were transferred to a normal drinking tap water.
      Control groups received corn oil vehicle, TQ alone or B(a)P alone. All mice were
      sacrificed at 12 weeks after the end of the treatment. Chromosome preparations
      were made of bone marrow. Cytogenetic end points screened were the frequencies of
      CAs and damaged cells induced. Daily intake of TQ after and before or during
      exposure to B(a)P significantly reduced the frequencies of CAs and damaged cells
      compared to the highly clastogenic activity of B(a)P alone.

PMID- 17011107
TI  - [Sequelae of haemangiomas: surgical treatment].
AB  - The cure without after-effect of an hemangioma is classic but sometimes the
      spontaneous involution, a premature surgical treatment or an evolutionary
      complication can be at the origin of a definitive after-effect. In these cases,
      the treatment of the hemangioma, often multidisciplinary, will be begun in a late
      way during the late childhood or the adolescence. Surgical excision of an excess
      tissue or of a wide scar, lipoaspiration of a fat remainder, lasertherapy and fat
      tissue reinjection are simple and mostly sufficient procedures. In the most
      complex cases, notably at the facial site, a surgery heavier as a rhinoplasty, a
      resection of lip, a local flap or orthognatic surgery can be necessary.

PMID- 17011108
TI  - Partial C-fiber ablation modulates diphenylmethane-4,4'-diisocyanate (MDI)
      induced respiratory allergy in Brown Norway rats.
AB  - Brown Norway (BN) rats were topically sensitized to polymeric diphenylmethane
      diisocyanate (MDI) and challenged with MDI-aerosol approximately every 2 weeks
      over a time period of 2 months. Half of the sensitized animals were pretreated
      with capsaicin for partial C-fiber defunctionalization. After the fourth
      challenge inflammatory and pro-inflammatory factors in bronchoalveolar lavage
      (BAL) fluid and cells and physiological delayed-onset breathing patterns were
      analyzed. The latter endpoint was examined in the capsaicin pretreated group
      before and after each challenge. Findings were compared against naive but
      repeatedly MDI-challenged BN rats. BAL-neutrophils, -protein, and -LDH as well as
      lung weights were significantly increased in the MDI-sensitized and challenged
      rats relative to the naive, challenged control rats. With regard to these
      endpoints, capsaicin pretreatment did not affect the responsiveness to MDI
      aerosol. In contrast, pro-inflammatory cytokines, the Th2 cell cytokine IL-4, and
      the CC-chemokine MCP-1 were significantly increased in BAL-cells of capsaicin
      pretreated and MDI-sensitized rats, whilst in the normal MDI-sensitized rats
      markedly less pronounced changes (if any) occurred. In the former group, IL-4 and
      MCP-1 were also significantly increased in the lung draining lymph nodes. Time
      related increased frequencies of delayed-onset responses were observed in MDI
      sensitized rats after subsequent MDI-challenges, however, differences between
      capsaicin pretreated and normal rats were not found. Despite the remarkable
      differences between normal and capsaicin pre-treated rats in the concentrations
      of pro-inflammatory and Th1-/Th2-cell specific cytokines, the inflammatory
      endpoints in BAL as well as the physiological measurements did not identify
      appreciable differences amongst these groups. This study included an ancillary
      study addressing the analysis of the modulating effect of capsaicin pre-treatment
      of naive Wistar rats exposed for single 6h to MDI-aerosol. The results indicated
      more pronounced changes on endpoints in the BAL-fluid of capsaicin-pretreated
      rats as compared to rats with intact C-fibers. This complex picture appears to
      suggest that C-fibers may modulate the allergic inflammatory response elicited by
      MDI-challenge. It appears that tachykinergic sensory C-fibers modulate the
      protective pathways against irritant-related lung inflammation and, similarly,
      also pro-inflammatory immunological factors modulating allergic inflammation.
      Although difficult to disentangle unequivocally the mechanisms involved, neuro
      immunological factors may be important in triggering and maintaining this complex
      disease and cytokine/chemokine patterns may not necessarily predict the
      functional outcome of test.

PMID- 17011109
TI  - Heavy metal transporters in Hemiascomycete yeasts.
AB  - We have compiled all known heavy metal transporters of the yeast Saccharomyces
      cerevisiae and identified their orthologs in four other species spanning the
      entire Hemiascomycete phylum. The 213 transporters belong to 27 distinct
      phylogenetic families distributed within the three classes: channels, secondary
      porters (permeases) and transport ATPases. They are present in all cellular
      membranes: plasma membranes, vacuoles, mitochondria, endoplasmic reticulum,
      nucleus, Golgi and various cytoplasmic vesicles. The major physiological heavy
      metals transported are: iron, manganese, zinc, copper, arsenite and cadmium. The
      major subfamilies that comprise the highest number of transporters are
      Siderophore-Iron Transporters (SIT) and CT2 (conjugated ABC transporters). They
      transport heavy metals (iron or cadmium, respectively) conjugated to organic
      chelators such as siderophores or glutathione. Both subfamilies are considerably
      amplified in the yeast Yarrowia lipolytica. The pattern of expansion and
      restriction of the subfamilies during the evolution of the different species is
      highly variable. The phylogenetic trees of the major transporters subfamilies
      distinguish homogenous clusters of transporters suggesting that possible
      different physiological or mechanistic functions evolved independently. We also
      validated the use of the Hemiascomycetes heavy metal transporters for
      identification of orthologs transporters in the pathogenic Basidiomycetes
      Cryptococcus neoformans.

PMID- 17011110
TI  - Changes of nuclear factor kappa B (NF-kappaB), cyclooxygenase-2 (COX-2) and
      matrix metalloproteinase-9 (MMP-9) in human myometrium before and during term
      labor.
AB  - OBJECTIVE: To investigate the changes of nuclear factor kappa B (NF-kappaB),
      cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in human term
      myometrium before and during term labor. STUDY DESIGN: Myometrium was obtained
      from women undergoing cesarean delivery at term before (n=16) and after labor
      (n=12). Immunostaining of NF-kappaB subunits (p65/p50) and Western blot analysis
      of NF-kappaB subunits, MMP-9 and COX-2 proteins were compared. Human term myocyte
      cultures were stimulated with IL-1beta. Activation of NF-kappaB was assessed by
      evaluating changes in the inhibitory protein IkappaB; regulation of COX-2 and MMP
      9 levels was studied using Western blot analysis and gelatin zymography. RESULTS:
      In contrast to a significant increase in the level of COX-2 and MMP-9 proteins,
      p65 and p50 decreased significantly in the after-labor group compared to the
      before-labor group. After treatment with IL-1beta, IkappaB was degraded by almost
      90% within 5 min and became undetectable by 15 min. IL-1beta stimulation
      increased the levels of COX-2 protein and the gelatinolytic activities of MMP-9,
      both of which were inhibited by NF-kappaB inhibitors. CONCLUSIONS: Human term
      labor is associated with changes in NF-kappaB and increased expression of COX-2
      and MMP-9 in the myometrium. NF-kappaB pathway activation and subsequent
      increments of COX-2 and MMP-9 were observed in human term myocyte cultures.

PMID- 17011111
TI  - A test for measuring the effects of enzyme inactivation.
AB  - In the single-enzyme, single-substrate reaction with non-mechanism-based enzyme
      inactivation, the formation of the product and inactivation of the enzyme occur
      independently. For this reaction, we show that the steady-state hypothesis is
      applicable even when degradation of the enzyme occurs. An equation for the rate
      of product formation has been derived and it shows Michaelis-Menten kinetics with
      an apparent Michaelis-Menten constant K(M)(app)=K(M)+K(delta) where K(delta) is
      the enzyme inactivation constant. Use of a Lineweaver-Burk plot yields values for
      K(M)(app), which can be used to estimate K(delta) and, consequently, the degree
      of enzyme inactivation in a particular experiment. We employ this methodology to
      estimate the inactivation constant for the arsenate reductase catalyzed
      production of arsenite with appreciable enzyme inactivation.

PMID- 17011112
TI  - Study on the influence of additives in an industrial calcium fluoride and
      waterworks sludge co-melting system.
AB  - This work explores the effect of additives on the pouring temperature in a
      waterworks and industrial calcium fluoride sludge co-melting system. Two kinds of
      sludge were mixed in various ratios to find a mixing ratio at which the operating
      temperature for subsequent additive tests was relatively low. Various proportions
      of either sodium carbonate (Na2CO3) or potassium carbonate (K2CO3) reagent were
      added to the mixed-sludge samples to elucidate the consequent changes in pouring
      temperature. The experimental results revealed that the pouring temperature was
      lowest when calcium fluoride was mixed with waterworks sludge in a ratio of 4:6
      (w/w). Adding sodium carbonate or potassium carbonate reagent to the mixed-sludge
      samples further reduced the pouring temperature. Increasing the amount of sodium
      carbonate did not significantly reduce the pouring temperature beyond that
      observed when 2% was added, suggesting that 2% was the optimal additional
      percentage of sodium carbonate. In contrast, the pouring temperature was
      increased when over 2% potassium carbonate was added to the mixed-sludge samples,
      revealing that the optimal additional percentage of potassium carbonate was also
      2%. These findings indicate that both sodium carbonate and potassium carbonate
      can be used as additives to increase the energy efficiency of the melting
      process, but sodium carbonate is more operationally convenient.

PMID- 17011113
TI  - Bulbourethral composite suspension for treatment of male-acquired urinary
      incontinence.
AB  - OBJECTIVES: We evaluated the efficacy of bulbourethral composite sling procedure
      in the treatment of male urinary incontinence after radical prostatectomy,
      transurethral resection of the prostate, or prostatic enucleation for benign
      prostatic hyperplasia, and posterior urethroplasty. METHODS: Between May 2000 and
      April 2005, a bulbourethral composite sling was performed in 26 patients with
      acquired urinary incontinence. Eight (30.8%) of these patients had severe urinary
      incontinence, and 18 (69.2%) had mild to moderate urinary incontinence. A
      polyester patch plus tension-free vaginal tape (TVT) device was used in the
      procedure. Prolene threads were attached to the two ends of polyester taper then
      passed from the perineal incision to a suprapubic incision with a TVT needle. The
      ends of the sutures and TVT were tied over the rectus fascia in the midline after
      repeated urethral pressure measurements reached 80-90 cm H2O. RESULTS: The follow
      up period was 8-54 mo (mean: 28.3). The primary procedure failed in one patient.
      Of the remaining 25 patients, 1 patient died of cerebral hemorrhage 2 yr
      postoperatively, and 2 patients had recurrent stress incontinence in 1.5 and 2 yr
      postsurgery, respectively. The recurrent incontinence was severe in one patient
      and mild (one to two pads per day) in the other. The remaining 22 patients
      maintained urination and continence. The total success rate (cure and improved)
      was 92% (23 of 25). CONCLUSIONS: Bulbourethral composite sling procedure is a
      minimally invasive, safe, effective surgical option in the treatment of male
      patients with mild to moderate incontinence, but is not suitable for severe
      incontinence. Temporary perineal discomfort or pain is a common complication of
      the procedure.

PMID- 17011114
TI  - Concomitant carcinoma in situ is a feature of aggressive disease in patients with
      organ-confined TCC at radical cystectomy.
AB  - OBJECTIVES: Carcinoma in situ (CIS) is a nonpapillary, high-grade, potentially
      aggressive, and unpredictable manifestation of transitional cell carcinoma (TCC)
      of the bladder. The aim of this study was to assess whether presence of
      concomitant CIS has a detrimental effect on cancer control after radical
      cystectomy. METHODS: The records of 812 consecutive patients who underwent
      radical cystectomy and pelvic lymphadenectomy for bladder TCC at three US
      academic centres were reviewed. Ninety-nine of 812 (12%) patients had CIS only at
      radical cystectomy and were excluded from the analyses. RESULTS: Three hundred
      thirty of the 713 (46.3%) patients had concomitant CIS at radical cystectomy.
      Patients with TCC involvement of the urethra were more likely to have concomitant
      CIS than not (61% vs. 40%, p=0.018). Concomitant CIS was significantly more
      common in patients with lower cystectomy stages and higher tumour grades. In
      univariate, but not multivariate, analysis, patients with concomitant CIS versus
      those without were at increased risk of disease recurrence (p=0.0371). In
      patients with organ-confined disease, concomitant CIS was an independent
      predictor of disease recurrence (p=0.048 and p=0.012, respectively) but not
      bladder cancer-specific mortality (p=0.160 and p=0.408, respectively) after
      adjusting for the effects of standard postoperative features. CONCLUSIONS:
      Concomitant CIS in the cystectomy specimen is common, and patients with
      concomitant CIS are at increased risk of urethral TCC involvement. The presence
      of concomitant CIS appears to confer a worse prognosis in patients with non
      muscle-invasive TCC treated with radical cystectomy.

PMID- 17011116
TI  - Up-regulation of VEGF-C secreted by cancer cells and not VEGF-A correlates with
      clinical evaluation of lymph node metastasis in esophageal squamous cell
      carcinoma (ESCC).
AB  - Tissue expression of VEGF-C correlates with lymph node involvement (LNI) in ESCC
      and serum VEGF-C (sVEGF-C) in a non-small cell lung cancer has been more accurate
      marker of LNI than chest CT. Despite LNI importance in ESCC, the usefulness of
      serum VEGF-C (sVEGF-C) as a disease and LNI marker in ESCC has not been
      investigated yet. We found elevated sVEGF-C in ESCC (17.40 vs. 10.57 ng/ml in
      controls, p<0.001). It proved to be a better ESCC marker than described
      elsewhere: CEA, CA19-9 and SCC-Ag, with: sensitivity--70%, specificity--81%,
      accuracy--83.7%. Analysis of sVEGF-C correlation with clinico-pathological cancer
      features revealed relation to LNI (N0: 15.77 vs. N1: 21.78 ng/ml, p=0.02),
      especially in advanced cancers. Serum VEGF-C as a marker of LNI was characterized
      by: sensitivity--76%, specificity--58%, accuracy--64.4%. No relation was observed
      between LNI and sVEGF-A or sVEGF-A/platelets (PLT). Because sVEGF-C was higher in
      N0 cancers (p<0.01), the tumor presence also up-regulates sVEGF-C. We found sVEGF
      C correlation with PLT and WBC: R=0.36 and R=0.32 (p<0.01). Nevertheless,
      analysis of PLT and WBC dependence on cancer features implies that elevation of
      sVEGF-C in N1 cancers is not related to them.

PMID- 17011115
TI  - Rater-dependent accuracy in predicting the spatial location of functional centers
      on anatomical MR images.
AB  - OBJECTIVES: The determination of eloquent cortex is essential when planning
      neurosurgical approaches to brain lesions. This study examined the abilities of
      medical personnel of various backgrounds to predict the location of functional
      cortex using anatomical information provided by MR imaging. PATIENTS AND METHODS:
      Neurosurgeons, neuroscientists, neuroradiologists, medical students and MR
      technologists viewed anatomical MR images acquired from patients with brain
      tumors and healthy controls. These five groups of raters were then asked to
      locate the primary motor hand, supplementary motor and primary auditory areas and
      their predictions were compared to fMRI data acquired from the same subjects.
      RESULTS: The overall mean distance from the center of the fMRI activation was
      2.38 cm. The neuroscientists performed the best and MR technologists performed
      the worst (mean distance from center of 1.83 and 3.04 cm, respectively, p<0.05).
      The difference between patients and controls was not significant. The mean
      distance by ROI was primary motor hand 2.03 cm, auditory area 2.06 cm and
      supplementary motor area 3.18 cm (p<0.05). Raters also performed best in the
      medial-lateral direction, compared to superior-inferior and anterior-posterior
      directions (mean distances from center 0.42, 1.04 and 1.81 cm, respectively).
      Finally, the approximate minimum fields of view necessary to capture the entire
      fMRI activations using the raters' predictions ranged from 5 to 15 cm, or 3 to 12
      cm larger than the fMRI activations. CONCLUSION: Medical personnel of various
      training perform poorly when using only anatomical information to predict the
      location of functional areas of cortex.

PMID- 17011117
TI  - Innovative safety valve selection techniques and data.
AB  - The new valve data resources and modeling tools that are available today are
      instrumental in verifying that that safety levels are being met in both current
      installations and project designs. If the new ISA 84 functional safety practices
      are followed closely, good industry validated data used, and a user's maintenance
      integrity program strictly enforced, plants should feel confident that their
      design has been quantitatively reinforced. After 2 years of exhaustive
      reliability studies, there are now techniques and data available to support this
      safety system component deficiency. Everyone who has gone through the process of
      safety integrity level (SIL) verification (i.e. reliability math) will appreciate
      the progress made in this area. The benefits of these advancements are improved
      safety with lower lifecycle costs such as lower capital investment and/or longer
      testing intervals. This discussion will start with a review of the different
      valve, actuator, and solenoid/positioner combinations that can be used and their
      associated application restraints. Failure rate reliability studies (i.e. FMEDA)
      and data associated with the final combinations will then discussed. Finally, the
      impact of the selections on each safety system's SIL verification will be
      reviewed.

PMID- 17011118
TI  - Biosorption of reactive dye using acid-treated rice husk: factorial design
      analysis.
AB  - A factorial experimental design technique was used to investigate the biosorption
      of reactive red RGB (lambda(max)=521 nm) from water solution on rice husk treated
      with nitric acid. Biosorption is favored because of abundance of biomass, low
      cost, reduced sludge compared to conventional treatment techniques and better
      decontamination efficiency from highly diluted solutions. Factorial design of
      experiments is employed to study the effect of four factors pH (2 and 7),
      temperature (20 and 40), adsorbent dosage (5 and 50mg/L) and initial
      concentration of the dye (50 and 250 mg/L) at two levels low and high. The
      efficiency of color removal was determined after 60 min of treatment. Main
      effects and interaction effects of the four factors were analyzed using
      statistical techniques. A regression model was suggested and it was found to fit
      the experimental data very well. The results were analyzed statistically using
      the Student's t-test, analysis of variance, F-test and lack of fit to define most
      important process variables affecting the percentage dye removal. The most
      significant variable was thus found to be pH.

PMID- 17011119
TI  - An assessment of structure and toxicity correlation in organochlorine pesticides.
AB  - Organochlorines are the most successful, profitably utilized and commercialized
      group of pesticides. They have gained huge popularity and prominence in a short
      span of time by virtue of their ability to control almost all kinds of pests
      including insect, fungi, rodent, etc. The toxicity of an individual pesticide to
      the pests is predominantly determined by its structure, the different moieties
      attached to parent compound, their spatial arrangements within molecule, nature
      of substituents, polarity, symmetry and asymmetry of molecules, the solubility
      and sorption values. The present paper discusses the toxicity in terms of LD(50)
      of organochlorine pesticides on the basis of their structures. Further, the mode
      of action of these pesticides has been discussed for a better understanding of
      toxicity. Finally an attempt has been made to understand the structure toxicity
      relationship in organochlorine pesticides.

PMID- 17011120
TI  - Kinetics of decolorization of azo dye by bipolar pulsed barrier discharge in a
      three-phase discharge plasma reactor.
AB  - Removal of amaranth, a commercial synthetic azo dye widely used in the dye and
      food industry, was examined as a possible remediation technology for treating dye
      contaminated water. Effects of various parameters such as gas flow rate, solution
      conductivity, pulse repetition frequency, etc., on decolorization kinetics were
      investigated. Experimental results show that an aqueous solution of 24 mg/l dye
      is 81.24% decolorized following 30 min plasma treatment for a 50 kV voltage and
      0.75 m(3)/h gas flow rate. Decolorization reaction of amaranth in the plasma
      reactor is a pseudo first order reaction. Rate constant (k) of decolorization
      increases quickly with increasing the applied voltage, pulse repetition frequency
      and the gas flow rate. However, when the applied voltage is beyond 50 kV and
      increases further, increase rate of k decreases. In addition, k decreases quickly
      when the solution conductivity increases from 200 to 1481 microS/cm. The
      decolorization reaction has a high rate constant (k=0.0269 min(-1)) when the
      solution pH is beyond 10. Rate constant k decreases with the decrease of pH and
      reaches minimum at a pH of about 5 (k(min)=0.01603 min(-1)), then increases to
      0.02105 min(-1) when pH decreases to 3.07. About 15% of the initial TOC can be
      degraded only in about 120 min non-thermal plasma treatment.

PMID- 17011121
TI  - Control of heavy metals during incineration using activated carbon fibers.
AB  - Activated carbon fibers (ACFs) were applied to control heavy metals in
      incineration flue gas. Three heavy metal species (Cr, Cd and Pb), three ACFs,
      various adsorption temperatures (150, 250 and 300 degrees C) and weights of ACFs
      were experimentally determined. The results indicated that the effects of the
      type of ACF and the weight of the ACFs on the solid-state Cr removal were
      insignificant. The extent of solid-state Cd and Pb removal was related to the
      knitting structure of ACFs and the physical characteristic of the metals. The
      removal efficiencies of the solid-state and gaseous metals at various reaction
      temperature followed the order 250>150>300 degrees C and 300>250>150 degrees C,
      respectively.

PMID- 17011122
TI  - Pseudo-second order models for the adsorption of safranin onto activated carbon:
      comparison of linear and non-linear regression methods.
AB  - Kinetic experiments were carried out for the sorption of safranin onto activated
      carbon particles. The kinetic data were fitted to pseudo-second order model of
      Ho, Sobkowsk and Czerwinski, Blanchard et al. and Ritchie by linear and non
      linear regression methods. Non-linear method was found to be a better way of
      obtaining the parameters involved in the second order rate kinetic expressions.
      Both linear and non-linear regression showed that the Sobkowsk and Czerwinski and
      Ritchie's pseudo-second order models were the same. Non-linear regression
      analysis showed that both Blanchard et al. and Ho have similar ideas on the
      pseudo-second order model but with different assumptions. The best fit of
      experimental data in Ho's pseudo-second order expression by linear and non-linear
      regression method showed that Ho pseudo-second order model was a better kinetic
      expression when compared to other pseudo-second order kinetic expressions.

PMID- 17011123
TI  - Comparison of Fenton and sono-Fenton bisphenol A degradation.
AB  - Degradation of bisphenol A (BPA) was carried out with the Fenton reagent with and
      without additional sonochemical treatment. The Fenton and the sono-Fenton
      decomposition of BPA showed that ultrasound irradiation of wastewater improved
      the wet oxidation process of 25 mg l(-1) BPA solutions. The sonochemical
      degradation of BPA was monitored using UV absorption and large volume injection
      packed capillary LC measurements.

PMID- 17011124
TI  - Simultaneous preconcentration and determination of copper, nickel, cobalt and
      lead ions content by flame atomic absorption spectrometry.
AB  - A sensitive and simple method for the simultaneous preconcentration of
      nutritionally important minerals in real samples has been reported. The method is
      based on the formation of metal complexes by 4,6-dihydroxy-2-mercaptopyrimidine
      (DHMP) loaded on activated carbon. The metals content on the complexes are then
      eluted using 5 mL 2M HNO(3) in acetone, which are detected by AAS at resonance
      line. In this procedure, minerals such as Cu, Ni, Pb and Co could be analyzed in
      one run by caring out the simultaneous separation and quantification of them. At
      optimum condition the response are linear over concentration range of 0.04-1.1
      microg mL(-1) for Ni(2+) and 0.04-1.0 microg mL(-1) for Cu(2+), Pb(2+) and
      Co(2+). The detection limits of each element are expressed as the amount of
      analytes in ng mL(-1) giving a signal to noise ratio of 3 are equal to 3.5, 3.4,
      2.9 and 8.4 for Ni(2+), Co(2+), Cu(2+) and Pb(2+). The sorption capacity was
      determined by saturating 0.5 g solid phase. The loading capacity are 0.54, 0.53,
      0.63 and 0.45 mg g(-1) for Ni(2+), Co(2+), Cu(2+) and Pb(2+). The ability of
      method for repeatable recovery of trace ion are 99.0, 98.9, 99.2 and 98.8 with
      R.S.D. of 1.4, 1.3, 1.2 and 1.4 for Ni(2+), Co(2+), Cu(2+) and Pb(2+). The low
      detection limits of these elements in this technique make it a superior
      alternative to UV-vis and in several applications, also an alternative to ICP-MS
      techniques. The method has been successfully applied for these metals content
      evaluation in some real samples including natural water, leaves of spinach and
      cow liver.

PMID- 17011125
TI  - Effect of gabaergic, glutamatergic, antipsychotic and antidepressant drugs on
      pilocarpine-induced seizures and status epilepticus.
AB  - This work was designed to study the influence of drugs during seizures and status
      epilepticus (SE) induced by pilocarpine and mortality in adult rats. Fluoxetine
      (10 and 20 mg/kg), NMDA (N-methyl-D-aspartate, 10 and 20 mg/kg), amitriptyline
      (25 and 50 mg/kg), ketamine (0.5 and 1.0 mg/kg), gabapentin (100 and 150 mg/kg)
      and pimozide (10 and 20 mg/kg) were administered intraperitoneally, 30 min prior
      to pilocarpine (400mg/kg, s.c.). The animals were observed (24h) to determine:
      number of peripheral cholinergic signs, tremors, stereotyped movements, seizures,
      SE, latency to first seizure and number of deaths after pilocarpine treatment.
      Fluoxetine, amitriptyline, NMDA, and pimozide had proconvulsant effects in both
      doses tested. Smaller and higher doses of these drugs no protected and increased
      pilocarpine-induced seizures and/or mortality. Gabapentin and ketamine protected
      against seizures and reduced the latency to first seizure. Thus, these results
      suggest that caution should be taken in the selection of pharmacotherapy and
      dosages for patients with epilepsy because of the possibility of potentiating
      convulsive process toxicity.

PMID- 17011126
TI  - Neuroprotective effect of pentosan polysulphate on ischemia-related neuronal
      death of the hippocampus.
AB  - Pentosan polysulphate (PPS) negatively charged sulphated glycosaminoglycan was
      studied in ischemia-related hippocampal neuronal death and compared with a low
      molecular weight of heparin, named dalteparin in rats. Transient global ischemia
      was produced by four vessel-occlusion, the occlusion of the bilateral common
      carotid arteries following the electrocautherization of the vertebral arteries.
      3mg/kg of PPS or 300IU/kg of dalteparin was administered i.v. immediately after
      7min-occlusion/reperfusion. Seven days after the operation, the animals were
      perfused with 4% paraformaldehyde, and paraffinized coronal brain sections
      measuring 6microm in thickness were stained with hematoxylin and eosin. Neuronal
      damage was then estimated as a ratio of the number of degenerated neurons to that
      of both the surviving and degenerated neurons in three distinct area of the CA1
      subfield. The ratio of neuronal death increased with the length of the occlusion
      time, at 5, 7 and 10min. Both PPS and dalteparin significantly inhibited the
      neuronal damage induced by 7min-occlusion. These results demonstrated that both
      PPS and dalteparin could thus protect brain neurons against ischemia/reperfusion
      induced damage thus suggesting that they may be potentially useful therapeutic
      agents for acute ischemic stroke.

PMID- 17011127
TI  - Pharmacological studies of the opioids, mood stabilizer and dopaminergic drugs on
      pilocarpine-induced seizures and status epilepticus.
AB  - This work was designed to study the influence of drugs during seizures and status
      epilepticus (SE) induced by pilocarpine and mortality in adult rats. Morphine
      (0.1 and 0.2 mg/kg), SCH 23390 (0.1 and 0.2 mg/kg), haloperidol (5 and 10mg/kg)
      and lithium (30 and 60 mg/kg) were administered intraperitoneally (i.p.), 30 min
      before to pilocarpine (400 mg/kg, s.c.). The animals were observed (24 h) to
      determine: number of peripheral cholinergic signs, tremors, stereotyped
      movements, seizures, SE, latency to first seizure and number of deaths after
      pilocarpine treatment. Morphine and haloperidol had proconvulsant effects in both
      doses tested. Smaller and higher doses of these drugs no protected and increased
      pilocarpine-induced seizures, SE and/or mortality. SCH 23390 protected against
      seizures, increased the latency to first seizure and reduced the mortality of the
      animals treated with pilocarpine Theses results suggest that dopamine receptor
      system receptor subtypes exert opposite functions on the regulation of convulsive
      activity. The morphine is proconvulsant in lower doses. The opioids in high doses
      tested exert an action proconvulsant during the establishment of epileptic
      activity induce by pilocarpine. The lithium no protected the animals against
      seizures induced by pilocarpine and is used which a model of epilepsy associated
      with lower doses of pilocarpine in several studies, suggesting absence of the
      effect anticonvulsants in rodents.

PMID- 17011128
TI  - High-level pyrantel resistance in the hookworm Ancylostoma caninum.
AB  - While anthelmintic resistance is now a widely recognized issue in the livestock
      industries, its existence within companion animal medicine has been rarely
      established conclusively. We undertook a placebo-controlled in vivo trial to
      measure the efficacy of pyrantel embonate against pooled isolates of the hookworm
      Ancylostoma caninum from Brisbane, Australia. A statistically significant fall in
      adult worm burden was observed among dogs in the pyrantel treatment group
      compared to the control dogs (178.0+/-24.5 versus 239.7+/-14.0; p=0.02), equating
      to an efficacy of just 25.7% (95% CI, 15.0-35.1%), as based upon reduction in
      mean worm burden. Analysis of faecal egg count trends through the course of the
      study revealed that egg counts rose in both control and pyrantel-treated dogs,
      with a greater rise observed in the latter group (11.6+/-8.3% versus 17.3+/-7.6%;
      p=0.04), despite the decrease in adult worm numbers in this group. Our results
      indicate that high-level anthelmintic resistance does occur in companion animal
      medicine, and highlight the need for greater vigilance and more judicious use of
      anthelmintics in small animal practice. They further indicate that the faecal egg
      count reduction test needs to be used with caution with this parasite.

PMID- 17011129
TI  - Ecology of the free-living stages of major trichostrongylid parasites of sheep.
AB  - Significant developments over recent decades make it timely to review the ecology
      of the major gastrointestinal nematode (GIN) species of sheep. These include the
      relentless development and spread of anthelmintic resistance in all of the major
      sheep production regions of the world, and the consequent drive towards
      integrated parasite management (IPM) systems incorporating non-chemotherapeutic
      strategies such as grazing management. The success of such programs is dependent
      on a detailed understanding of the environmental influences on the free-living
      stages of the nematode lifecycle. Major reviews of the subject were conducted
      prior to 1980, however considerable work has been completed since, including the
      development of mathematical models describing the epidemiology of GIN infection.
      Knowledge of the temperature thresholds for free-living development has also
      improved, while investigations of moisture influences and interactions with
      temperature have allowed more effective exploitation of environmental effects for
      IPM. This review re-evaluates our understanding of the factors that determine the
      success or failure of the free-living phases of the lifecycle in light of these
      developments. Temperature and moisture are the dominant influences on the free
      living stages of Haemonchus contortus, Teladorsagia circumcincta and
      Trichostrongylus colubriformis, with the effects of pasture conditions playing a
      significant modulating role. Early in the free-living phase, the developmental
      success of the three GIN species is limited by susceptibility to cold
      temperatures. In general, H. contortus is most susceptible, followed by T.
      colubriformis and then T. circumcincta. The length of the development cycle is
      dependent largely on temperature, with development rate increasing at warmer
      temperatures. However, in order for development to proceed to the infective
      larval stage, addition of moisture is generally required. There has been
      considerably less work quantifying the effects of moisture on free-living
      development, although it is clear that H. contortus is most susceptible to
      desiccation during the pre-infective stages. Once the infective stage is reached,
      the influences of temperature and moisture on survival are less important,
      resulting in considerable survival times under conditions lethal to pre-infective
      stages. However, hot, dry conditions can be lethal for infective larvae of all
      three species, while extreme cold is also lethal with significant species
      variation. While the existing body of knowledge is substantial, the
      interpretation of many studies and comparison between them is complicated by
      inadequate description of, or variation in, the environmental measurements used.
      Confounding the effects of environmental variables on development to infective
      stage is the migration of larvae from the faeces and subsequent survival on
      pasture. There is a need to build on recent efforts to explore interaction
      between the effects of temperature and moisture, and also the trend to more
      closely simulate field conditions in laboratory studies. We propose a logical
      framework for future ecological investigations to overcome some of these
      problems, facilitate the development of a more integrated dataset on the subject
      and improve prediction of free-living development.

PMID- 17011130
TI  - Primary emergency surgical airway for trismus caused by electrical burn.

PMID- 17011131
TI  - An outcome analysis of patients transferred to a regional burn center: transfer
      status does not impact survival.
AB  - BACKGROUND: Optimal burn care is provided at specialized burn centers. Given the
      geographic location of these centers, many burn patients receive initial
      treatment at local emergency departments prior to transfer. The purpose of this
      study was to determine whether patients transferred from other facilities have
      worse outcomes than those admitted directly from the field. STUDY DESIGN: A
      retrospective cohort study was performed comparing the outcomes of patients
      admitted to our burn center directly from the field with patients requiring
      transfer from a preliminary care facility. The outcomes of interest were
      mortality, length of stay, length of stay/TBSA burned, number of operations and
      hospital charges. Poisson regression or Cox proportional hazards model was used
      to evaluate differences in outcomes after adjusting for potential confounders.
      RESULTS: From 2000 to 2003 a total of 1877 patients were admitted to our burn
      center and 953 (51%) were transferred from a preliminary care facility. No
      difference (p<0.05) was found in length of stay, number of operations, hospital
      charges and mortality between the two cohorts. CONCLUSIONS: This study
      demonstrates that patients transferred to a regional burn center from local
      hospitals have equivalent mortality, length of stay and hospital charges as those
      admitted directly from the field.

PMID- 17011132
TI  - Clinical forensic evidence in burns: rescuer burns.
AB  - In the literature no systematic study is available on rescuer burn for victims of
      burn injury. This is a retrospective study of nine patients (five admitted and
      four outpatients) were treated in this hospital as rescuer burns in 3.5 years.
      All nine patients were males. Average age of the patient treated on outpatient
      basis was 47 years (ranging between 44 and 52) and total burn area ranged for 1
      4%. Average age of the five patients treated on inpatient basis was 32.6 years
      (ranging between 30 and 34). The total burn area ranged from 14.5 to 38%. During
      the period of study, in addition to nine rescuer burns, one patient sustained
      burn before the rescue attempt due to the victim hugging the rescuer. Based on
      the study of patterns of burn, these patients were found to have three grades of
      burn injury: Grade 1--upper extremity involvement only. (A) only one upper
      extremity involvement, (B) both upper extremities involvement, Grade 2--upper
      extremity/extremities and face involvement, Grade 3--upper extremity/extremities,
      face-neck, adjacent chest and lower extremity involvement.

PMID- 17011133
TI  - Characteristics of burn patients at a major burn center in Shanghai.
AB  - In China, burns are becoming a major cause of morbidity and mortality with large
      societal and economic implications. To date, there is little epidemiological data
      on burns in China to direct prevention efforts. This study describes the
      characteristics of burn patients admitted to a major burn center in Shanghai
      using a burn registry developed in Toronto, Canada. A retrospective review of
      burn patients discharged from the Shanghai's Rui Jin Hospital Burn Unit, between
      March 1st 2002 and April 30th 2003, was conducted. Of 527 patients discharged,
      307 were acute burn patients and 302 (98.4%) had complete data to be included in
      the study. There were 214 (71%) males and 88 (29%) females with a male to female
      ratio of 2.4:1. The median age was 30 years, and the median total body surface
      area burned was 10%. The majority of burns occurred at work (58%), and the most
      frequent etiology was flames (39%) followed by scalds (31%) and contact with hot
      objects (15%). Sixteen (5%) patients had inhalation injury and six (2%) patients
      died. There were 70 (23%) children (0-14 years), 221 (73%) adults (15-59 years)
      and 11 (4%) seniors (60 years and above). Children had more scald burns (83%) and
      the majority (83%) occurred at home. Adults had more flame burns (46%) and the
      majority (79%) were work-related injuries. Seniors had more flame burns (73%) and
      the majority (55%) occurred in domestic incidents. Seniors had deeper burns (13%,
      p=0.005), required more escharotomies (55%, p=0.002), required more operations
      (2, p=0.051) and had higher mortality (36%, p<0.001) than other age groups. These
      results provide compelling evidence for performing population-based studies to
      identify risk factors that are susceptible to modification in each age group.

PMID- 17011134
TI  - Atrial fibrillation may be a vascular disease: the role of the pulmonary vein.
AB  - Recent years have seen an enormous amount of experimental and clinical research
      into role of the pulmonary veins (PVs) in atrial fibrillation (AF). The PVs
      contain cardiomyocytes with easily inducible arrhythmogenic activity due to the
      enhanced automaticity, induction of triggered activity, and genesis of
      microreentrant circuits. The enhanced automaticity, induced triggered activity,
      either alone or in combination with the reentrant mechanisms, may play a role in
      the initiation of PVs AF. Detailed mapping studies suggest that reentry within
      the PVs is most likely responsible for their arrhythmogenicity. There is no doubt
      that the PVs represent the most important source of arrhythmogenic activity in
      patients with paroxysmal AF. In AF patients with risk factors for development of
      AF, the presence of the pathological situation is important in enhancing the PV
      arrhythmogenic activity. Coronary sinus or superior vena cava may also be a
      source of rapid repetitive electrical activity during AF. Thus, AF should be
      considered a kind of vascular disease. Moreover, in patients with paroxysmal AF
      originating from the PVs, a wide spectrum of atrial arrhythmias may coexist,
      including paroxysms of atrial premature, tachycardia, flutter and fibrillation.
      This kind of arrhythmias should be named as PV atrial arrhythmias. These new
      views will help understand the mechanism, diagnosis and treatment method for AF.

PMID- 17011135
TI  - Accompaniment of primary Raynaud's phenomenon with epilepsy: A similarity in the
      pathophysiologic process?

PMID- 17011137
TI  - Glucose-6-phosphate-dehydrogenase deficiency is a possible risk factor for the
      development of toxic epidermal necrolysis.

PMID- 17011136
TI  - Does the aqueous humor have a role in mitogen-activated protein kinase (MAPK)
      intracellular signaling in Glaucoma?
AB  - Glaucoma is a common blinding disease worldwide. Glaucoma treatment today is
      based on reduction of aqueous humor production or increase aqueous humor
      drainage. By medical manipulation, the treatment goal is to reduce the main risk
      factor, elevated intra ocular pressure. Here we hypothesize that the aqueous
      humor has a role, beside oxygen and nutrient supply, in transferring signaling to
      the trabecular meshwork. This signaling might be delivered from the ciliary body
      were the aqueous humor is produced, or from the lens or the cornea. Recently in
      our lab we proposed that MAPKs present in the aqueous humor are a novel signal
      involved in glaucoma pathology. Here we show that this pathway exists at an
      unexpected, extracellular media. Western blot analysis of aqueous humor from
      congenital glaucomatic rabbits and a rat model of induced elevated intra ocular
      pressure (IOP) were found to express several signaling members of the MAPK
      family. Although these members are usually found in an intracellular environment,
      they can be detected at an extracellular environment, namely the aqueous humor.
      These signaling proteins are found also in normal eyes. Moreover the MAPK
      signaling proteins are found in the active phosphorylated form and in non-active
      form in elevated IOP animals as well as in the control, normal IOP groups.
      Understanding the signaling cascade, at the aqueous humor, opens a new area for
      treatment of glaucoma patients. By interfering with the signaling cascade, taking
      place at a reachable location, the anterior chamber, we will be able to
      manipulate these protein effects on the trabecular meshwork.

PMID- 17011138
TI  - Atrial fibrillation: rhythm control offers no advantage over rate control for
      some, but not all.
AB  - Atrial fibrillation (AF) is not a benign condition. Although AF is the most
      common sustained cardiac arrhythmia, the management of AF remains controversial.
      In recent years, several clinical trials comparing rhythm control with rate
      control for AF management found that rhythm control offers no advantage over rate
      control, but the findings may not apply equally to all patients. The main point
      is the high risk of AF recurrence in these trials and the toxic effects and poor
      efficacy of presently available antiarrhythmic drugs negate the benefit of rhythm
      control. Rhythm control should be considered as the preferred initial therapy if
      sinus rhythm had been maintained in a higher proportion of patients. For the
      moment, the optimal strategy to treat AF should be individualized, with a bias
      towards rate control if patients are at high risk for arrhythmias or can be kept
      asymptomatic. Rhythm control may still be justified in younger patients or
      patients who still have symptoms despite adequate rate control. In addition,
      patients with new or first-episode AF often warrant at least an initial trial of
      rhythm control.

PMID- 17011139
TI  - The 1918 influenza A epidemic in the city of Sao Paulo, Brazil.
AB  - The 1918 pandemic H1N1 outbreak in the city of Sao Paulo is revisited. The
      outbreak lasted for 10 weeks and reached 116,771 officially recorded cases
      amongst 523,194 inhabitants. The total number of deaths summed up to 5331, with a
      lethality rate of 4.5% and an overall mortality rate of around 1%. We propose a
      mathematical model that tallies available data with good accuracy and allows the
      estimation of the basic reproductive number, R(0). The model showed a remarkably
      good accuracy in retrieving the real data from Sao Paulo city outbreak
      considering the total number of recorded cases and deaths and the timing of the
      outbreak. The basic reproduction number calculated of 2.68 can be compared to
      estimates carried out for other flu strains, like the estimates for H3N2, whose
      values ranged from 1.5 to 2.5. We hypothesize that the Southern parts of the
      world in which there was relatively little impact of the Great War, like South
      America, suffered a much lower H1N1 influenza mortality as compared with that
      reported for the Northern hemisphere heavily affected by the I World War.

PMID- 17011140
TI  - In atherogenesis, the apoptosis of endothelial cell itself could directly induce
      over-proliferation of smooth muscle cells.
AB  - Over-proliferation of SMC (smooth muscle cell) is one characteristics of
      atherosclerosis. One well accepted mechanism is that the decrease of ECs
      (endothelial cells) induced by over apoptosis leads to endothelial dysfunction,
      which in turn results in over-proliferation of SMC. Obviously, the mechanism
      works after endothelial apoptosis. Compared with necrosis, apoptosis is time and
      energy consuming. The question is why the cell ends in the form of apoptosis
      instead of necrosis. From the evolutionary standpoint, apoptosis has some useful
      functions other than removing the damaged or unwanted cells. Recent studies
      showed that cells nearby the apoptotic ones began to proliferate and
      differentiate before apoptosis and the apoptotic signals could induce the near
      cells to proliferate without the death of cells. Apparently, some mechanism in
      apoptosis results in the proliferation of cells. So, we hypotheses that
      endothelial apoptosis can directly induce the over-proliferation of SMC.

PMID- 17011141
TI  - Degeneration after sexual differentiation in hydra and its relevance to the
      evolution of aging.
AB  - Aging occurs in most multicellular animals, yet some primitive animals do not
      show any sign of aging. This raises the following question: How have metazoans
      acquired the trait of aging in the course of evolution? Comparative studies of
      various species have provided a clue to this question by showing that sexually
      reproducing organisms predominantly undergo aging. The evolutionary theory
      "pleiotropy" also postulates aging as a price for facilitating the reproduction
      in the early life stage of an organism. For investigating the association between
      sexual reproduction and aging, a sexual phase-inducible organism in a laboratory
      would be suitable. One of such organisms is hydra, a genus of Cnidaria. Asexual
      hydra has been considered to be immortal, but there is the possibility that hydra
      undergoes aging after sexual reproduction. To search for signs of aging in hydra,
      we studied sexually differentiated Hydra oligactis at the individual and cellular
      levels. As a result, we found a significant decline in the capacities for food
      capture, contractile movements, and reproduction. More importantly, we discovered
      an exponential increase in the mortality rate of the population. These
      observations suggest that the degenerative process in H. oligactis represents the
      aging process. Furthermore, we found that the number of germ cells increased,
      whereas the number of somatic cells concomitantly decreased. The observed change
      of the cell composition is thus consistent with the "pleiotropy" theory of aging.

PMID- 17011142
TI  - Intelligent design and biological complexity.
AB  - Before any intelligence can appear, a world endowed with the potential for being
      experienced as a body of phenomena has to be existent. Indeed, if there is to be
      an intelligence, there first has to be something intelligible. Hence, when an
      intelligence is present, "creation" must already have taken place. Nevertheless,
      biological complexity has been deemed by some to be one of the privileged points
      of insertion of a supernatural intelligence endowed with temporal and causal
      primacy. In the course of a critical review, it is pointed out that the spectacle
      of nature's spontaneous tinkering with the structures and performances of
      informational macromolecules and with interactive connections among these
      molecules suggests that intelligence and design are absent from evolution. Nor is
      intelligent design required for explaining biological complexity, which can
      increase spontaneously as a byproduct of combinatorial intermolecular gambles and
      of the restoration of molecular damage wrought by mutations. One of the possible
      molecular pathways to spontaneous evolutionary increases in complexity is
      described.

PMID- 17011143
TI  - Effects of repeated welding fumes exposure on the histological structure and
      mucins of nasal respiratory mucosa in rats.
AB  - To investigate the effects of welding fumes on the histological structure and
      properties of mucins of the nasal respiratory mucosa, Sprague-Dawley rats were
      exposed to manual metal arc-stainless steel (MMA-SS) welding fumes at a
      concentration of 56-76 mg/m3 total suspended particulates for 2 h per day in an
      inhalation chamber for 90 days. Experimental animals were sacrificed at 2 h, 15,
      30, 60 and 90 days after exposure. Loss of cilia, desquamation of epithelial
      cells, mucigenous epithelial cells and destruction of nasal septal glands were
      observed frequently in the welding fumes-exposed groups. These changes became
      more severe as the exposure continued. The amount of neutral mucins in goblet
      cells in the welding fumes-exposed group had a tendency to increase, the amount
      of sulfomucins decreased, while the sialomucins increased as the exposure
      continued. Mucinogenic epithelial cells, not visible in the control group,
      contained minimal to small amounts of neutral mucins. In the dorsal septal
      glands, neutral mucins not visible in the control group appeared, and neutral
      mucins in the ventral septal glands increased slightly. These results indicate
      that the observed changes in the properties of mucins due to inhalation of
      welding fumes may play roles in protection against toxicants.

PMID- 17011144
TI  - Lysosomes as the target of yessotoxin in invertebrate and vertebrate cell lines.
AB  - The toxic effects of the algal polyether phycotoxin yessotoxin (YTX) are studied
      in the insect fat body IPLB-LdFB and the mouse fibroblast NIH3T3 cell lines. Our
      experiments confirm the cytotoxic action exerted by the toxin in both insect and
      mammalian cells, but morphological observations, TUNEL experiments and
      electrophoretic evalution of DNA integrity failed to evidence a clear pro
      apoptotic role for YTX. In both IPLB-LdFB and NIH3T3 cell lines, neutral red and
      acridine orange stainings, together with evaluation of acid phosphatase activity
      demonstrate that YTX first damages lysosomal vesicles. This is then followed by a
      progressive depolymerization of actin microfilaments, as shown by phalloidin
      fluorescent immunostaining. Overall, our data identify in early lysosomal damage
      and the subsequent cytoskeletal disruption two common steps related to YTX
      toxicity towards metazoan cells.

PMID- 17011145
TI  - The effects of a low dose of cabergoline on induction of estrus and pregnancy
      rates in anestrous bitches.
AB  - This is the first report of successful induction of normal estrus and ovulation
      in breeder bitches with as a low dose as 0.6 microg/kg/day of cabergoline
      formulation marketed for use in women. Sixty-one pure breed bitches from various
      breeds were used in the study at their already determined periods of anestrus.
      Twenty-four dogs formed the control group, while 37 bitches were administered
      with two different doses of cabergoline (recommended dose group, n=10, 5
      microg/kg/day and low dose group, n=27, 0.6 microg/kg/day). Induced estrus rates
      and mean treatment and proestrus durations of dogs in these two dose groups were
      compared. At the second phase of the study, the effects of 500 IU human chorionic
      gonadotropin (hCG) administered on days 1 and 3 of estrus induced by the low dose
      of cabergoline, on the duration of behavioral estrus, ovulation rates, pregnancy
      rates and the number of offspring were investigated. For this purpose, the dogs
      with signs of proestrus (22/27) following the treatment in the low dose group
      were assigned into two subgroups. Five hundred IU of hCG (Pregnyl, Organon,
      Turkey) was intramuscularly administered to eight of these dogs [low dose (hCG+)
      group] on days 1 and 3 of estrus. The remaining 14 dogs were not treated with hCG
      [low dose (hCG-) group]. An aqueous solution of cabergoline (Dostinex, Pharmacia,
      Italy) was orally administered until 2 day after the onset of proestrus or for a
      maximum of 42 days. Blood samples were taken daily from all treatment and 11
      control bitches during the first five days of behavioral estrus to measure
      progesterone concentrations. In the recommended dose and low dose groups, estrus
      was induced between days 8-45 and 4-48 (mean: 23.63+/-14.33 and 24.41+/-14.31
      days), in the ratio of 80.0 and 81.5%, respectively (p>0.05). In both dose
      groups, post-treatment interestrous intervals were significantly shorter than
      both those of the control group and their own pre-treatment interestrous
      intervals (p<0.05). Ovulation rates, pregnancy rates and mean number of offspring
      delivered by the dogs in the recommended dose, low dose (hCG-), low dose (hCG+)
      and control groups were found to be similar (p>0.05). However, the mean duration
      of behavioral estrus of the dogs in the low dose (hCG+) group was found to be
      significantly longer compared to dogs in all other groups (p<0.05). In both dose
      groups, no correlation could be found between the anestrus stages and treatment
      durations (p>0.05). Shortly, it has been concluded from the study that (1) normal
      and fertile estrus can be induced more economically in bitches during different
      stages of anestrus using as a low dose of 0.6 microg/kg of cabergoline
      formulation marketed for use in women, and that (2) hCG injections on days 1 and
      3 of the estrus induced by this method has no positive effects on the ovulation
      rates, pregnancy rates and the number of offspring per pregnancy.

PMID- 17011146
TI  - Effects of maturational age of recipient oocytes and activation conditions on the
      development of porcine fetal fibroblast nuclear transfer embryos.
AB  - This study was conducted to evaluate the nuclear remodeling patterns and the
      developmental potential of porcine fetal fibroblast nuclear transfer embryos
      (NTs) following the maturational age of recipient oocytes and activation
      conditions. Donor cells were transferred into the enucleated oocytes that were
      matured for 36 or 44h. Electrofused embryos were cultured in PZM-3 for 6 days
      without activation treatment (EF group). Some of these embryos were additionally
      activated by electric stimulus (ES; EF+ES group) or a combination of ES and DMAP
      (EF+ES+D group) before culture. The reconstituted embryos were fixed 2.5h after
      fusion to evaluate the nuclear remodeling patterns. The nuclear remodeling
      pattern of NTs reconstituted with 44 h-matured recipients showed a tendency to
      form a pronucleus-like structure, while that of NTs reconstituted with 36 h
      matured recipients showed a tendency to undergo a premature chromosome
      condensation (PCC) and form one set of chromatin clump. In EF+ES+D group,
      blastocyst development was significantly increased regardless of maturational age
      of recipient oocytes (P<0.05). The result indicates that additional activation
      treatment is necessary to induce the activation of embryos reconstituted with 36
      h-matured recipients, and treatment with the combination of electrical stimuli
      and DMAP could enhance the blastocyst formation rate of porcine NTs reconstituted
      with both 36 h- and 44 h-matured recipient oocytes.

PMID- 17011147
TI  - Changes in reproductive indices in Chuvashian women whose maturation was during
      World War II.
AB  - OBJECTIVES: The aim of the present study was to evaluate whether Chuvashian women
      whose maturation was during World War II and the subsequent rehabilitation period
      were different from women born at other times in terms of age at menarche and age
      at menopause. DESIGN: The cohort included 745 Chuvashian females aged 18-90
      years; age at menarche (N=653), ranged from 10 to 24 years (mean 15.42+/-2.11).
      Data regarding menopausal age was obtained from 322 females born between 1915 and
      1950 (mean 48.5+/-4.6). We computed descriptive statistics of the age of
      menopause and the age of menarche for different birth cohorts; we compared the
      mean values by Student's t-test and the variances by F-test. RESULTS: The
      "expected" maturation period of women whose age at menarche >20 and most women
      whose age at menopause < or =38 was between 1939 and 1950. Women whose age at
      menarche >20 showed normal parameters regarding age at menopause, and women whose
      age at menopause was < or =38 showed normal parameters of age at menarche. The
      variances of age at menopause in women born from 1925 to 1936 was almost two-fold
      higher than in women born earlier and afterwards (p=0.0003). The difference in
      the mean ages was significant for both menarche (p=0.005) and menopause
      (p=0.001). CONCLUSION: Periods of socioeconomic disasters such as war and famine
      can influence women's age at menarche and age at menopause. Women, whose
      maturation occurred during or immediately after World War II, showed a higher
      mean age at menarche and a wider dispersion of age at menopause than other women.

PMID- 17011148
TI  - Antimicrobial, anti-inflammatory, anti-ulcer and antioxidant activities of
      Carlina acanthifolia root essential oil.
AB  - The root of Carlina acanthifolia All. (Asteraceae) has been traditionally used in
      the treatment of various disorders including stomach and skin diseases. We
      studied antimicrobial, anti-inflammatory, anti-ulcer and antioxidant activities
      of Carlina acanthifolia root essential oil, in order to validate some of the
      ethnopharmacological claims. Antimicrobial activity was tested on 15 bacteria and
      three strains of fungi using the agar diffusion and broth microdilution methods.
      In assessing anti-inflammatory activity the carrageenan-induced rat paw oedema
      test was used, while ethanol-induced stress gastric ulcer test in rats was used
      in testing anti-ulcer activity. Antioxidant properties were evaluated trough the
      effect of the essential oil on lipid peroxidation (TBA assay) and its capability
      of quenching 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH radicals. The oil
      expressed significant antimicrobial activity, being the most active against Gram
      (+) bacteria: Streptococcus pyogenes, Enterococcus faecalis, Bacillus subtilis
      and against Candida albicans. In all applied concentrations, Carlina acanthifolia
      root essential oil reduced carrageenan-induced rat paw oedema in dose-dependent
      manner, achieving high degree of anti-inflammatory activity. The effect was
      comparable with that of indomethacin used as a reference drug. In the ethanol
      induced stress gastric ulcer test in rats, it was shown that the tested essential
      oil produced significant dose-dependent gastroprotective activity. The results
      also pointed out substantial and dose-dependent antioxidant activity of the
      investigated essential oil, with carlina oxide as the main antioxidant component.

PMID- 17011149
TI  - [Current epidemiology of microbial low respiratory tract infections].
AB  - The recent literature brings nothing new since it provides only fragmented,
      though undoubtedly useful, studies which remain within the prevalence interval
      for the different bacterias. The occurrence of germs varies with time and space;
      nevertheless, whatever the studied series and the site of the studies, the 3 most
      frequent causal germs belong to the following five strains: Streptococcus
      pneumoniae, Influenza A, Mycoplasma pneumoniae, Haemophilus influenzae, and
      Legionella pneumophila. Thus, 90% of all documented pneumoniae appear to be
      caused by the following pathogens: Pneumococcus; most frequent in hospitalized
      patients; Mycoplasma, Chlamydia and respiratory viruses were predominant in
      outpatients, with great variations; Staphylococcus and enterobacteriace may be
      encountered, mostly in elderlies with major debilitating diseases; association of
      germs, generally including pneumococcus, are increasingly identified. Last, in
      25% to 50% of cases, the causal agent is not known. Recently, some Staphylococcus
      meticillin-resistant were identified. The diagnosis of viruses (as well as that
      of atypical bacterias) seems to have improved, thanks to the use of PCR though
      the interest of such a diagnosis remains questionable, except for epidemiological
      studies, as well as the relevance of this type of test in clinical practice.
      Nothing really new has come out on the epidemiology of acute bronchitis, while in
      bacterial exacerbation of COPD, attention focused on the colonizing or infective
      role of H. influenzae in the genesis of bronchus inflammation.

PMID- 17011150
TI  - [Characteristics of clumping factor- and protein A-negative methicillin-resistant
      Staphylococcus aureus identified in Poland].
AB  - AIM: The aim of this study was to investigate the phenotypic and genotypic
      properties of clumping factor- and protein A- negative MRSA. METHODS: Two hundred
      ninety-four strains were studied. The production of protein A was determined by
      immunoblotting, clumping factor (CF) and coagulase by conventional tests with
      rabbit plasma. The presence of nuc gene and mecA gene was identified by PCR. The
      presence of clfA and spa genes was determined for CF- and protein A-negative
      strains and then phage typing was performed using two sets of phages and gene
      typing by RFLP of the spa gene. RESULTS: Sixteen (5.4%) CF- and protein A
      negative MRSA were isolated. All of them produced coagulase and thermostable
      nuclease (except for one). nuc, mecA, spa and clfA genes were observed in all
      strains. The same RLFP pattern, but with different phage types and resistance
      profiles to antibiotics, was observed in all strains. CONCLUSIONS: CF- and
      protein A-negative methicillin resistant S. aureus isolated in Poland do not come
      from a single clone and the absence of CF and protein A is not caused by the
      deletion of clfA and spa genes.

PMID- 17011151
TI  - For the special issue: the nematode Caenorhabditis elegans in aging research.

PMID- 17011152
TI  - Split renal function measured by triphasic helical CT.
AB  - PURPOSE: To present a method for calculating split renal function solely from
      routine triphasic helical computed tomography (CT). SUBJECTS AND METHODS: We
      retrospectively included 26 adult patients who received renal scintigraphy and
      triphasic CT within 4 weeks in the years 2003 and 2004. All scans were performed
      using a standard abdominal protocol. Split renal function was calculated as
      relative single-kidney glomerular filtration rate (GFR) using a simplified "two
      point Patlak plot" technique. As a reference method, split renal function was
      determined from renal scintigraphy using the standard technique. RESULTS: Linear
      correlation between the two methods was r=0.91, split renal function
      (CT)=0.0266+0.9573 x split renal function (scintigraphy). CONCLUSION: Split renal
      function can be measured accurately by minimally extended triphasic CT.

PMID- 17011153
TI  - The role of health professionals in childhood injury prevention: a systematic
      review of the literature.
AB  - OBJECTIVE: To systematically review the literature to explore health
      professionals' knowledge, attitudes and practices and their role in childhood
      injury prevention. METHODS: MEDLINE (1966-September Week 1 2005), EMBASE (1980
      2005 Week 37), CINAHL (1982-September Week 1 2005), BRITISH NURSING INDEX (1985
      September 2005) and PsychINFO (1967-August Week 5 2005) were searched using
      relevant 'medical subheadings' (for MEDLINE, EMBASE and CINAHL) and 'thesaurus
      terms' (for PsychINFO). RESULTS: Twenty-five primary studies were retrieved, the
      majority of which were surveys. Health professionals' knowledge was reported to
      be variable, although generally they have a positive attitude towards childhood
      injury prevention. Even with adequate knowledge and positive attitudes there
      appear to be barriers in prevention practice. CONCLUSION: There continues to be a
      need for high quality research specifically looking at how to change practice.
      Nevertheless, although training may be effective at increasing health
      professionals' knowledge and changing their attitudes, legislative and
      engineering measures may ultimately more effective at reducing the burden of
      childhood injuries. PRACTICE IMPLICATIONS: Barriers to practice for health
      professionals need to be taken into account. No matter how knowledgeable nor how
      positive their attitudes to childhood injury prevention if barriers to practice
      are not addressed we will move no closer to reducing the burden of injuries in
      childhood. Those health professionals who are positive about their role may be
      best suited to continue to raise the issue campaigning for legislative and
      engineering changes which can reduce childhood injuries.

PMID- 17011154
TI  - Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND):
      process modelling of pilot study.
AB  - OBJECTIVE: To determine the effects of a structured education program on illness
      beliefs, quality of life and physical activity in people newly diagnosed with
      Type 2 diabetes. METHODS: Individuals attending a diabetes education and self
      management for ongoing and newly diagnosed (DESMOND) program in 12 Primary Care
      Trusts completed questionnaire booklets assessing illness beliefs and quality of
      life at baseline and 3-month follow-up, metabolic control being assessed through
      assay of HbA1c. RESULTS: Two hundred and thirty-six individuals attended the
      structured self-management education sessions, with 97% and 64% completing
      baseline and 3-month follow-up questionnaires. At 3 months, individuals were more
      likely to: understand their diabetes; agree it is a chronic illness; agree it is
      a serious condition, and that they can affect its course. Individuals achieving a
      greater reduction in HbA1c over the first 3 months were more likely to agree they
      could control their diabetes at 3 months (r=0.24; p=0.05), and less likely to
      agree that diabetes would have a major impact on their day to day life (r=0.35;
      p=0.006). CONCLUSION: Pilot data indicate the DESMOND program for individuals
      newly diagnosed with Type 2 diabetes changes key illness beliefs and that these
      changes predict quality of life and metabolic control at 3-month follow-up.
      PRACTICE IMPLICATIONS: Newly diagnosed individuals are open to attending self
      management programs and, if the program is theoretically driven, can successfully
      engage with the true, serious nature of diabetes.

PMID- 17011155
TI  - The impact of illustrations on public understanding of the aim of cancer
      screening.
AB  - OBJECTIVE: To study the effectiveness of visual illustrations in improving
      people's understanding of the preventive aim of flexible sigmoidoscopy (FS)
      screening. METHODS: Three-hundred and eighteen people aged 60-64 were offered an
      appointment to attend FS screening and randomly allocated to receive either
      written information alone or written information plus illustrations. The
      illustrations showed the adenoma-carcinoma sequence and how it can be interrupted
      by removing polyps found during FS. Telephone interviews were conducted with a
      randomly selected sub-set of people prior to their screening appointment to
      assess their knowledge and understanding of the test (n=65). The interviews were
      tape-recorded, transcribed and content analysed by researchers blind to the
      condition people had been allocated to. RESULTS: In the written information only
      group, 57% understood that the test was looking for polyps rather than just
      cancer, whilst in the group who received written information and illustrations,
      84% understood this. Logistic regression analyses confirmed that addition of
      illustrations resulted in significantly better understanding (OR=3.75; CI: 1.16
      12.09; p=0.027), and this remained significant controlling for age, gender and
      Townsend scores (an area-based measure of deprivation) (OR=10.85; CI: 1.72-68.43;
      p=0.01). CONCLUSION: Illustrations improved understanding of the preventive aim
      of FS screening. PRACTICE IMPLICATIONS: Pictoral illustrations could be used to
      facilitate patient understanding of screening.

PMID- 17011156
TI  - Inverse regulation of leptin mRNA expression by short- and long-chain fatty acids
      in cultured bovine adipocytes.
AB  - Leptin is an adipose tissue-derived cytokine plays key roles in the regulation of
      food intake and energy expenditure. However, regulatory mechanisms of leptin gene
      expression are not fully elucidated in ruminants that utilize short-chain fatty
      acids (SCFA), known as volatile fatty acids, as principal energy sources. In this
      study, we determined effects of SCFA and long-chain fatty acids (LCFA) on leptin
      expression in bovine adipocytes. Bovine stromal vascular cells isolated from
      subcutaneous adipose tissue of Holstein cows were cultured to confluence and
      treated sequentially with dexamethasone and isobutylmethylxanthine for 2 days and
      insulin and troglitazone for 12 days to achieve full differentiation to
      adipocytes. The cells started to accumulate lipids 4 days after the onset of
      treatment, with increased mRNA expression of leptin, as well as aP2, adiponectin,
      and PPAR-gamma. Removal of fetal calf serum and reduction of glucose in the
      culture medium of differentiated adipocytes decreased leptin mRNA expression.
      Subsequent addition of acetate, butyrate, or propionate dose-dependently restored
      and rather increased leptin expression, while addition of LCFA suppressed it. The
      stimulatory effect of acetate was abolished by prior treatment of the cells with
      pertussis toxin and by addition of LCFA. Furthermore, cows fasted for 48h and fed
      thereafter, elaborate reduced and increased plasma leptin levels, respectively.
      Thus, these results suggest that plasma leptin levels in cows are inversely
      controlled at the transcription level by VFA and LCFA, and that the effects of
      SCFA possibly act through a G protein-coupled receptor for SCFA.

PMID- 17011157
TI  - [Delayed discovery in an ICU patient of a superior vena cava perforation after
      subclavian-venous catheterization].
AB  - Perforation is a central venous catheterization complication mainly observed in
      children. Usually, patients develop sudden shock early after catheterization. We
      report an asymptomatic and delayed superior vena cava perforation after
      subclavian venous adult catheterization discovered by contrast injection
      tomography.

PMID- 17011158
TI  - [Myiasis in intensive care unit: interest of entomological survey].

PMID- 17011159
TI  - Berberine induces apoptosis through a mitochondrial/caspase pathway in human
      promonocytic U937 cells.
AB  - Berberine, an isoquinoline plant alkaloid, is known to generate a wide variety of
      biochemical and pharmacological effects. To elucidate the molecular mechanism of
      berberine-induced antiproliferative activities, the human promonocytic U937 cells
      were used. Berberine exhibited dose-dependent antiproliferative effects.
      Morphological evidence of apoptosis, including apoptotic DNA fragmentation, were
      observed in cells treated with 75 microg ml(-1) of berberine for 24h. Flow
      cytometry analysis revealed that berberine had no effect on cell cycle profile of
      U937 cells, however, sub-G(0) fraction (apoptotic cell population) was detected.
      The percentage of sub-G(0) fraction of cells treated with 75 microg ml(-1) of
      berberine was 25.3+/-1.6%. Berberine induces significant changes in mitochondrial
      membrane potential of U937 cells. The highest tested concentration of berberine
      decreased the mitochondrial membrane potential to 15.8+/-2.4% of control.
      Additionally, berberine-treated cells had an elevated level of ROS production.
      Activation of caspase-9 and caspase-3 was also detected, with no caspase-8
      activation observed. Taken together, the results clearly demonstrate that
      berberine induces apoptosis of U937 cells through the mitochondrial/caspase
      dependent pathway.

PMID- 17011160
TI  - Experimental exposure of arsenic in cultured rat intestinal epithelial cells and
      cell line: toxicological consequences.
AB  - Arsenic is a naturally occurring metalloid and the drinking water contamination
      by inorganic arsenic remains a major public health problem. The trivalent arsenic
      (arsenite) is more toxic than the pentavalent form (arsenate), and is known to
      cause gastrointestinal toxicity. Specific immortal cell lines are considered to
      be suitable for toxicity screening and testing of chemicals as they are easy to
      handle and possess most of the biochemical pathways present in the corresponding
      cells present in vivo. The present study was designed to evaluate and compare the
      in vitro toxicity of arsenite on rat intestinal epithelial cell line (IEC-6) and
      primary cultures of rat intestinal epithelial cells (IEC). To evaluate in vitro
      toxicity, cultures of IEC and IEC-6 cells were assessed for viability,
      morphometric analysis, membrane transport enzymes and structural constituents for
      membrane damage, dehydrogenase activity test for respiratory and energy producing
      processes and esterase activity test for intra and extra cellular degradation,
      following the post exposures to arsenite (0-20 ppm). Significantly similar
      concentration-dependent changes in these toxicity-screening parameters in IEC and
      IEC-6 were observed. Highest tested concentration of arsenite (20 ppm) was found
      to be detrimental in both IEC and IEC-6. Furthermore, to evaluate arsenite
      toxicity in epithelial cells of rat intestine, intestinal loops were filled with
      arsenite solutions and incubated for 30 min in situ. In situ studies also showed
      a significant arsenite concentration-dependent decline in epithelial cell
      membrane transport enzyme activities and total hexose and sialic acid contents.
      Concomitant release of membrane enzymes, hexose and sialic acid in the intestinal
      luminal fluid following higher arsenite exposures further indicated partial
      membrane damage. Similar morphological changes in IEC and IEC-6 were also
      evident. These findings also suggest that IEC-6 cell lines are suitable for
      initial screening of gastrointestinal cellular toxicity caused by arsenite.

PMID- 17011161
TI  - Modulatory effects of Echinacea purpurea extracts on human dendritic cells: a
      cell- and gene-based study.
AB  - Echinacea spp. are popularly used as an herbal medicine or food supplement for
      enhancing the immune system. This study shows that plant extracts from root [R]
      and stem plus leaf [S+L] tissues of E. purpurea exhibit opposite (enhancing vs
      inhibitory) modulatory effects on the expression of the CD83 marker in human
      dendritic cells (DCs), which are known as professional antigen-presenting cells.
      We developed a function-targeted DNA microarray system to characterize the
      effects of phytocompounds on human DCs. Down-regulation of mRNA expression of
      specific chemokines (e.g., CCL3 and CCL8) and their receptors (e.g., CCR1 and
      CCR9) was observed in [S+L]-treated DCs. Other chemokines and regulatory
      molecules (e.g., CCL4 and CCL2) involved in the c-Jun pathway were found to be up
      regulated in [R]-treated DCs. This study, for the first time, demonstrates that
      E. purpurea extracts can modulate DC differentiation and expression of specific
      immune-related genes in DCs.

PMID- 17011162
TI  - Environmental pyrethroid and organophosphorus insecticide exposures and sperm
      concentration.
AB  - BACKGROUND: There is growing concern that poisoning and other adverse health
      effects are increasing because organophosphorous (OP) insecticides are now being
      used in combination with pyrethroid (PYR) insecticides to enhance the toxic
      effects of PYR insecticides on target insects, especially those that have
      developed PYR resistance. OBJECTIVES: We conducted a pilot biomonitoring study to
      determine whether men in our reproductive cohort study were being exposed to
      pesticides environmentally by virtue of frequenting an agricultural setting.
      METHODS: We screened 18 randomly selected urine samples collected from male
      participants of reproductive age for 24 parent compounds and metabolites of
      pesticides and examined the results in relation to sperm concentration. RESULTS:
      Results showed high prevalence of exposure to OP and PYR pesticides and our
      preliminary analyses provided some suggestion that the higher exposure group had
      lower sperm concentration. CONCLUSIONS: The potential of OP/PYR mixtures to have
      enhanced human toxicity needs more research attention.

PMID- 17011163
TI  - Global attraction and stability for Cohen-Grossberg neural networks with delays.
AB  - We consider a class of Cohen-Grossberg neural networks with delays. We prove the
      existence and global asymptotic stability of an equilibrium point and estimate
      the region of existence. Furthermore, we show that the trajectories of the neural
      networks with positive initial data will stay in the positive region if the
      amplification function satisfies a divergent condition. We also establish the
      existence of a globally attracting compact set for more general networks. We
      estimate this compact set explicitly in terms of the network parameters from
      physiological and biological models. Our results can be applied to neural
      networks with a wide range of activation functions which are neither bounded nor
      globally Lipschitz continuous such as the Lotka-Volterra model. We also give some
      examples and simulations.

PMID- 17011164
TI  - Robust Bayesian clustering.
AB  - A new variational Bayesian learning algorithm for Student-t mixture models is
      introduced. This algorithm leads to (i) robust density estimation, (ii) robust
      clustering and (iii) robust automatic model selection. Gaussian mixture models
      are learning machines which are based on a divide-and-conquer approach. They are
      commonly used for density estimation and clustering tasks, but are sensitive to
      outliers. The Student-t distribution has heavier tails than the Gaussian
      distribution and is therefore less sensitive to any departure of the empirical
      distribution from Gaussianity. As a consequence, the Student-t distribution is
      suitable for constructing robust mixture models. In this work, we formalize the
      Bayesian Student-t mixture model as a latent variable model in a different way
      from Svensen and Bishop [Svensen, M., & Bishop, C. M. (2005). Robust Bayesian
      mixture modelling. Neurocomputing, 64, 235-252]. The main difference resides in
      the fact that it is not necessary to assume a factorized approximation of the
      posterior distribution on the latent indicator variables and the latent scale
      variables in order to obtain a tractable solution. Not neglecting the
      correlations between these unobserved random variables leads to a Bayesian model
      having an increased robustness. Furthermore, it is expected that the lower bound
      on the log-evidence is tighter. Based on this bound, the model complexity, i.e.
      the number of components in the mixture, can be inferred with a higher
      confidence.

PMID- 17011165
TI  - Support vector classifiers via gradient systems with discontinuous righthand
      sides.
AB  - Gradient dynamical systems with discontinuous righthand sides are designed using
      Persidskii-type nonsmooth Lyapunov functions to work as support vector machines
      (SVMs) for the discrimination of nonseparable classes. The gradient systems are
      obtained from an exact penalty method applied to the constrained quadratic
      optimization problems, which are formulations of two well known SVMs. Global
      convergence of the trajectories of the gradient dynamical systems to the solution
      of the corresponding constrained problems is shown to be independent of the
      penalty parameters and of the parameters of the SVMs. The proposed gradient
      systems can be implemented as simple analog circuits as well as using standard
      software for integration of ODEs, and in order to use efficient integration
      methods with adaptive stepsize selection, the discontinuous terms are smoothed
      around a neighborhood of the discontinuity surface by means of the boundary layer
      technique. The scalability of the proposed gradient systems is also shown by
      means of an implementation using parallel computers, resulting in smaller
      processing times when compared with traditional SVM packages.

PMID- 17011166
TI  - EcR and Usp, components of the ecdysteroid nuclear receptor complex, exhibit
      differential distribution of molecular determinants directing subcellular
      trafficking.
AB  - Ecdysteroids coordinate development, reproduction and other essential biological
      processes in insects and other arthropods through the receptor which is a
      heterodimer of two members of the nuclear receptors superfamily, the ecdysteroid
      receptor (EcR) and the Ultraspiracle (Usp). Although the transcriptionally active
      EcR/Usp heterocomplex is believed to be the only functional form of the receptor,
      there are data indicating that EcR may be involved in the mediation of the non
      genomic effects outside of the nucleus. Since the nucleocytoplasmic shuttling
      could be a key element determining participation of the single nuclear receptor
      molecule both in the genomic and non-genomic functions we have analyzed nuclear
      import and export properties of the EcR and Usp from Drosophila melanogaster. We
      show for the first time that both receptors exhibit differential distribution of
      the nuclear localization and nuclear export signals (NLSs and NESs). In
      particular, the Usp which exhibits exclusively nuclear localization in all cell
      types analyzed, contains apparently only NLS activity within the DNA-binding
      domain. In contrast, the three known EcR isoforms (A, B1 and B2) are mosaics of
      elements which can potentially mediate their nucleocytoplasmic shuttling. We have
      found two active NESs in ligand binding domain and NLS activity within the DNA
      binding domain of all isoforms. Simultaneously we demonstrate that B1 and A
      isoforms possess an additional NLS activity localized in AB regions. We speculate
      that this characteristic, along with the previously reported structural
      pliability of the EcR molecule, allows the single receptor to evoke many
      different genomic as well as non-genomic ecdysteroid-dependent responses.

PMID- 17011167
TI  - Osteopetrosis complicated by osteomyelitis of the mandible: a case report
      including characterization of the osteopetrotic bone.
AB  - A case of a 53-year-old Japanese man with osteopetrosis complicated by
      osteomyelitis of the mandible is presented. The patient experienced frequent
      exacerbations and remissions of osteomyelitis of the mandible, despite undergoing
      several surgical debridements and sequesterectomies with appropriate
      antimicrobial therapy, for 3 years. Finally, the patient underwent mandibular
      segmental resection followed by reconstruction with a titanium reconstruction
      plate. Fifty-one months after surgery there is no evidence of recurrent
      osteomyelitis of the mandible, suggesting that a more radical surgical approach
      is preferable for patients with severe complications resulting from
      osteopetrosis. Also presented here are the histopathological and biochemical
      features of the osteopetrotic bone. The osteopetrotic cortical bone was morbidly
      sclerotic with compact and irregular laminations. Degradation of osteocytes in
      the osteopetrotic bone was due to hypoxia and lack of nutrition resulting from
      osteosclerosis. There were no significant differences between osteopetrotic and
      normal bone according to X-ray diffraction, Fourier transform infrared
      spectroscopy, collagen content or mineral content. Micro-Vickers hardness
      measurements showed that osteopetrotic bone was significantly harder than normal
      bone, and the standard deviation of hardness was greater in osteopetrotic bone.
      Such a loss of integrity in osteopetrotic bone is considered to be a primary
      reason for the greater risk of a variety of complications such as pathological
      fracture and refractory osteomyelitis.

PMID- 17011168
TI  - Irradiation exacerbates cortical cytopathology in the Eker rat model of tuberous
      sclerosis complex, but does not induce hyperexcitability.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized
      by multi-organ pathologies. Most TSC patients exhibit seizures, usually starting
      in early childhood. The neuropathological hallmarks of the disease - cortical
      tubers, containing cytopathological neuronal and glial cell types - appear to be
      the source of seizure initiation. However, the contribution of these aberrant
      cell populations to TSC-associated epilepsies is not fully understood. To gain
      further insight, investigators have attempted to generate animal models with TSC
      like brain abnormalities. In the current study, we focused on the Eker rat, in
      which there is a spontaneous mutation of the TSC2 gene (TSC2+/-). We attempted to
      exacerbate TSC-like brain pathologies with a "second-hit" strategy - exposing
      young pups to ionizing irradiation of different intensities, and at different
      developmental timepoints (between E18 and P6). We found that the frequency of
      occurrence of dysmorphic neurons and giant astrocytes was strongly dependent on
      irradiation dose, and weakly dependent on timing of irradiation in Eker rats, but
      not in irradiated normal controls. The frequency of TSC-like pathology was
      progressive; there were many more abnormal cells at 3 months compared to 1 month
      post-irradiation. Measures of seizure propensity (flurothyl seizure latency) and
      brain excitability (paired-pulse and post-tetanic stimulation studies in vitro),
      however, showed no functional changes associated with the appearance of TSC-like
      cellular abnormalities in irradiated Eker rats.

PMID- 17011169
TI  - Clozapine specifically alters the arachidonic acid pathway in mice lacking
      apolipoprotein D.
AB  - Apolipoprotein D (apoD), a member of the lipocalin superfamily of lipid-binding
      proteins, exhibits abundant expression within the CNS of many species, including
      humans; however, its physiological role remains unclear. Treatment with atypical
      antipsychotic drugs, especially clozapine, results in elevation of apoD
      expression levels in rodent brain and in human plasma samples. In order to
      further explore the role of apoD in mechanisms of clozapine function, we have
      measured a panel of membrane fatty acids and membrane lipids in brain from drug
      treated apoD knock-out mice. Mice received clozapine (10 mg/kg/day) in their
      drinking water for 28 days and forebrain samples were analyzed using high
      performance liquid chromatography and capillary gas chromatography. We identified
      significant differences in the levels of membrane fatty acids in response to
      clozapine treatment specifically in the brains of apoD knock-out mice, but not
      wild-type (wt) mice. The most striking observations were decreases in the levels
      of fatty acids related to metabolism of arachidonic acid (AA), which is a known
      binding partner for apoD. These include the precursor to arachidonic acid,
      linoleic acid (LA; 18:2n6c), arachidonic acid itself (20:4n6) and the elongation
      product of arachidonic acid, adrenic acid (22:4n6). We further report increases
      in LA, eicosadienoic acid and docosahexaenoic acid in apoD knock-out compared to
      wild-type mice. These findings implicate an important apoD/AA interaction, which
      may be necessary for clozapine function.

PMID- 17011170
TI  - Minor physical anomalies across ethnic groups in a first episode psychosis
      sample.
AB  - Minor physical anomalies (MPAs) are more prevalent amongst individuals with
      psychosis, supporting a neurodevelopmental model for psychotic disorders. The aim
      of this study was to investigate the possibility that neurodevelopmental
      adversity contributes to the excess of psychosis found in some ethnic groups in
      the UK. Subjects with first onset psychosis and healthy neighbourhood controls
      were enrolled in the AESOP study in South East London and Nottingham between 1997
      and 1999. MPA rates were estimated in four broad ethnic groupings (White, African
      Caribbean, Black African and Other). Patients (n=245) had a higher mean total MPA
      score than healthy controls (n=158). This held true across each of the four
      ethnic groupings. The results of this study suggest that neurodevelopmental
      factors play a role in the aetiology of psychosis across all ethnic groups.

PMID- 17011171
TI  - Up-regulation of NPY gene expression in hypothalamus of rats with experimental
      chronic renal failure.
AB  - Anorexia is possibly one of the most important causes of malnutrition in uremic
      patients. The cause of this abnormality is still unknown. Considering that: (a)
      NPY is one of the most important stimulants of food intake; (b) eating is a
      central nervous system regulated process and (c) NPY is expressed in
      hypothalamus, we hypothesized that the decrease of NPY gene expression in the
      hypothalamus could be an important factor contributing to anorexia associated
      with uremic state. In contrast to the prediction, the results presented in this
      paper indicate that the NPY gene expression in the hypothalamus of chronic renal
      failure (CRF) rats was significantly higher than in the hypothalamus of control
      (pair-fed) rats. Moreover, we found that serum NPY concentration in CRF rats was
      higher than in control (pair-fed) animals. The increase of plasma NPY
      concentration in CRF rats may be due to the greater synthesis of the neuropeptide
      in liver, since higher level of NPY mRNA was found in liver of CRF rats. The
      results obtained revealed that experimental chronic renal failure is associated
      with the increase of NPY gene expression in hypothalamus and liver of rats.

PMID- 17011172
TI  - Effects of retinoic acid on the development of liver fibrosis produced by carbon
      tetrachloride in mice.
AB  - The role of retinoic acid (RA) in liver fibrogenesis was previously studied in
      cultured hepatic stellate cells (HSCs). RA suppresses the expression of alpha2(I)
      collagen by means of the activities of specific nuclear receptors RARalpha,
      RXRbeta and their coregulators. In this study, the effects of RA in fibrogenesis
      were examined in carbon tetrachloride (CCl4) induced liver fibrosis in mice. Mice
      were treated with CCl4 or RA and CCl4, along side control groups, for 12weeks. RA
      reduced the amount of histologically detectable fibrosis produced by CCl4. This
      was accompanied by a attenuation of the CCl4 induced increase in alpha2(I)
      collagen mRNA and a lower (2-fold versus 3-fold) increase in liver
      hydroxyproline. Furthermore, RA reduced the levels of 3-nitrotyrosine (3-NT)
      protein adducts and thiobarbituric acid (TBA) reactive substance (TBARS) in the
      liver, which are formed as results of oxidative stress induced by CCl4 treatment.
      These in vivo findings support our previous in vitro studies in cultured HSC of
      the inhibitory effect of RA on type I collagen expression. The data also provide
      evidence that RA reduces CCl4 induced oxidative stress in liver, suggesting that
      the anti-fibrotic role of RA is not limited to the inhibition of type I collagen
      expression.

PMID- 17011173
TI  - Dynamic expression of Runx1 in skin affects hair structure.
AB  - The three mammalian Runx transcription factors, some of which are known to be
      involved in human genetic diseases and cancer, are pivotal players in embryo
      development and function as key regulators of cell fate determination and
      organogenesis. Here, we report the expression of Runx1 during the development of
      hair and other skin appendages in the mouse and describe the effect of Runx1 on
      the structural hair output. In hair follicles, where the three Runx proteins are
      expressed, Runx1 expression is most prominent in both mesenchymal and epithelial
      compartments. The epithelial expression includes the hair keratin forming layers
      of the hair shaft and the bulge, where interestingly, Runx1 is co-expressed with
      keratin 15, a putative hair follicle stem cell marker. In the hair mesenchyme,
      during early stages of hair morphogenesis, Runx1 is expressed in a discrete
      dermal sub-epithelial layer, while at later stages it is found in a hair cycle
      dependent pattern in the dermal papilla. To elucidate the function of Runx1 in
      the hair follicle we have generated a Runx1 epidermal conditional knockout and
      found that the mutant mice display a remarkable structural deformation of the
      zigzag hair type. The data delineate Runx1 as a novel specific marker of several
      hair follicle cell types and sheds light on its role in hair morphogenesis and
      differentiation.

PMID- 17011174
TI  - [Severity assessment of acute diarrhoea].
AB  - Clinician should recognize any life-threatening causes of diarrhoea, such as
      intussusceptions, surgical abdomen, and haemolytic uraemic syndrome. The
      following clinical features should alert: abdominal pain with tenderness, with or
      without guarding, pallor, jaundice, oligo-anuria, bloody diarrhoea, systemically
      unwell out of proportion to the level of dehydration, shock. The risk of
      dehydration is related to age (highest in young infants<6 months), and frequency
      of watery stools (>8/day) and vomiting (>2/day before 1 year and >4/day after 1
      year), but these historical points have a moderate sensitivity. The severity of
      dehydration is rarely estimated with accuracy in terms of weight loss (third
      sector with full colon, absence of accurate baseline pre-dehydration weight).
      Combinations of examination signs perform markedly better than any individual
      sign in predicting dehydration (poor rate agreement, clinically unhelpful
      likelihood ratio). The presence of at least three signs better correlate with
      dehydration. Laboratory tests are not helpful. New studies are mandatory to
      validate severity scoring systems.

PMID- 17011175
TI  - Temporal abstraction in intelligent clinical data analysis: a survey.
AB  - OBJECTIVE: Intelligent clinical data analysis systems require precise qualitative
      descriptions of data to enable effective and context sensitive interpretation to
      take place. Temporal abstraction (TA) provides the means to achieve such
      descriptions, which can then be used as input to a reasoning engine where they
      are evaluated against a knowledge base to arrive at possible clinical hypotheses.
      This paper surveys previous research into the development of intelligent clinical
      data analysis systems that incorporate TA mechanisms and presents research
      synergies and trends across the research reviewed, especially those associated
      with the multi-dimensional nature of real-time patient data streams. The
      motivation for this survey is case study based research into the development of
      an intelligent real-time, high-frequency patient monitoring system to provide
      detection of temporal patterns within multiple patient data streams. RESULTS: The
      survey was based on factors that are of importance to broaden research into
      temporal abstraction and on characteristics we believe will assume an increasing
      level of importance for future clinical IDA systems. These factors were: aspects
      of the data that is abstracted such as source domain and sample frequency,
      complexity available within abstracted patterns, dimensionality of the TA and
      data environment and the knowledge and reasoning underpinning TA processes.
      CONCLUSION: It is evident from the review that for intelligent clinical data
      analysis systems to progress into the future where clinical environments are
      becoming increasingly data-intensive, the ability for managing multi-dimensional
      aspects of data at high observation and sample frequencies must be provided.
      Also, the detection of complex patterns within patient data requires higher
      levels of TA than are presently available. The conflicting matters of
      computational tractability and temporal reasoning within a real-time environment
      present a non-trivial problem for investigation in regard to these matters.
      Finally, to be able to fully exploit the value of learning new knowledge from
      stored clinical data through data mining and enable its application to data
      abstraction, the fusion of data mining and TA processes becomes a necessity.

PMID- 17011176
TI  - Determination of endogenous tissue inflammation profiles by LC/MS/MS: COX- and
      LOX-derived bioactive lipids.
AB  - Cyclooxygenase and lipoxygenase arachidonate products, including prostaglandins
      (PGs), leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETEs), are known
      to modulate inflammation within tissues and can serve as important etiologic
      factors in carcinogenesis. Eicosanoid content in tissues is typically determined
      either as a single molecular species through antibody-based assays or by high
      performance liquid chromatography after addition of an exogenous substrate such
      as arachidonic acid. Unfortunately, the methods currently in use are either time
      consuming or complicated. Here we report a method for simultaneously identifying
      eicosanoids appearing as endogenous bioactive lipids in in vivo settings using
      LC/MS/MS. The analyses indicate marked differences in endogenous eicosanoid
      content between malignant tissue types suggesting a need for selective
      therapeutic approaches. As a demonstration of the utility of the method, we
      present data to show that the technique can be used to distinguish
      eicosapentaenoic acid-derived formation of PGE(3) from PGE(2) in murine prostate
      tissue. The method has also been applied to an examination of endogenous
      eicosanoid metabolism in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral
      cancer in hamsters demonstrating the inflammatory nature of this type of cancer
      with elevated levels of both PGE(2) and LTB(4). In addition, the concentration of
      the eicosanoid 13-hydroxyoctadecadienoic acid was 67.6% lower in DMBA treated
      specimens than in control specimens. Thus, our method provides a powerful tool
      for measuring modulation of eicosanoid metabolites in various preclinical and
      clinical tissues and may be useful in studies of the endogenous changes in
      eicosanoid metabolism at various stages of cancer development.

PMID- 17011177
TI  - Morphological and ecological similarities: wood-boring beetles associated with
      novel xylose-fermenting yeasts, Spathaspora passalidarum gen. sp. nov. and
      Candida jeffriesii sp. nov.
AB  - Ascomycete yeasts that both ferment and assimilate xylose were reported
      previously as associates of insects living in woody substrates. Most notable have
      been reports of Pichia stipitis-like yeasts that are widely associated with the
      wood-boring beetle, Odontotaenius disjunctus (Coleoptera: Passalidae), in the
      eastern United States. Our continuing investigation of insect gut yeasts has lead
      to the discovery of two new xylose-fermenting yeasts that phylogenetic analysis
      places as sister taxa. The beetle hosts, O. disjunctus and Phrenapates bennetti
      (Coleoptera: Tenebrionidae), are similar in habitat and appearance, and the
      presence of similar gut yeasts is an additional common feature between them. Here
      we describe the new yeast genus Spathaspora, the type species S. passalidarum,
      and its sister taxon Candida jeffriesii and discuss their natural history,
      including a comparison with Pichia stipitis, another member of a guild of xylose
      fermenting yeasts with similar metabolic traits. In addition a morphologically
      distinct yeast ascospore type is described for Spathaspora.

PMID- 17011178
TI  - Landfill leachate treatment using a rotating biological contactor and an upward
      flow anaerobic sludge bed reactor.
AB  - This paper describes the feasibility of an aerobic system (rotating biological
      contactor, RBC) and a biological anaerobic system (upward-flow anaerobic sludge
      bed reactor) at small scale for the treatment of a landfill leachate. In the
      first phase of the aerobic system study, a cyclic-batch RBC system was used to
      select perforated acetate discs among three different acetate disc
      configurations. These discs were chosen on the basis of high COD removal (65%)
      and biological stability. In the second phase, the RBC system (using four stages)
      was operated continuously at different hydraulic retention times (HRT), at
      different rotational speeds, and with varying organic concentrations of the
      influent leachate (2500-9000mgL(-1)). Forty percent of the total surface area of
      each perforated disc was submerged in the leachate. A COD removal of about 52%
      was obtained at an HRT of 24h and a rotational speed of 6rpm. For the anaerobic
      system, the reactor was evaluated with a volumetric organic load of 3273g-COD m(
      3) day(-1) at an HRT of 54, 44, 39, 24 and 17h. At these conditions, the system
      reached COD removal efficiencies of 62%, 61%, 59%, 44% and 24%, respectively.

PMID- 17011179
TI  - Enrichment of PCDDs/PCDFs in the cooling system of municipal solid waste
      incineration plants.
AB  - This study measured the levels of polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans (PCDDs/PCDFs), destroyed or formed in combustors
      and re-synthesized in cooling systems. For the proper control of PCDDs/PCDFs in
      municipal solid waste (MSW) incinerators, three grate-type MSW incinerators were
      selected, two of which had boilers, and one of which had a water spray tower
      (WST) as a cooling system. At the combustor outlets, dusts were in the range of
      1640-4270 mg/Sm3 and PCDDs/PCDFs were in the range of 0.103-2.619 ng-TEQ/Sm3,
      showing the different values according to the grate structure of combustor and
      the flow direction of flue gas. After the flue gases passed through the cooling
      system, PCDDs/PCDFs at the waste heat boiler (WHB) outlets were enriched to
      levels that were 10.8-13.6 times higher than those at the furnace outlets, but
      PCDDs/PCDFs at the WST outlet was reduced to 5% of the level found at the furnace
      outlet. The emission patterns, such as the ratio of PCDFs to PCDDs, the ratio of
      gaseous-phase to particulate-phase PCDDs/PCDFs, and the compositional percentiles
      of each 2,3,7,8-substituted congener varied according to the types of air
      pollution control devices (APCDs). Reducing re-synthesis in the cooling system
      rather than enhancing the removal efficiencies of the APCDs seems to be more
      effective for lowering the levels of PCDDs/PCDFs in MSW incineration plants.

PMID- 17011180
TI  - Application of a unique server-based oligonucleotide probe selection tool toward
      a novel biosensor for the detection of Streptococcus pyogenes.
AB  - We developed a software program for the rapid selection of detection probes to be
      used in nucleic acid-based assays. In comparison to commercially available
      software packages, our program allows the addition of oligotags as required by
      nucleic acid sequence-based amplification (NASBA) as well as automatic BLAST
      searches for all probe/primer pairs. We then demonstrated the usefulness of the
      program by designing a novel lateral flow biosensor for Streptococcus pyogenes
      that does not rely on amplification methods such as the polymerase chain reaction
      (PCR) or NASBA to obtain low limits of detection, but instead uses multiple
      reporter and capture probes per target sequence and an instantaneous
      amplification via dye-encapsulating liposomes. These assays will decrease the
      detection time to just a 20 min hybridization reaction and avoid costly enzymatic
      gene amplification reactions. The lateral flow assay was developed quantifying
      the 16S rRNA from S. pyogenes by designing reporter and capture probes that
      specifically hybridize with the RNA and form a sandwich. DNA reporter probes were
      tagged with dye-encapsulating liposomes, biotinylated DNA oligonucleotides were
      used as capture probes. From the initial number of capture and reporter probes
      chosen, a combination of two capture and three reporter probes were found to
      provide optimal signal generation and significant enhancement over single
      capture/reporter probe combinations. The selectivity of the biosensor was proven
      by analyzing organisms closely related to S. pyogenes, such as other
      Streptococcus and Enterococcus species. All probes had been selected by the
      software program within minutes and no iterative optimization and re-design of
      the oligonucleotides was required which enabled a very rapid biosensor
      prototyping. While the sensitivity obtained with the biosensor was only 135 ng,
      future experiments will decrease this significantly by the addition of more
      reporter and capture probes for either the same rRNA or a different nucleic acid
      target molecule. This will lead to the possibility of detecting S. pyogenes with
      a rugged assay that does not require a cell culturing or gene amplification step
      and will therefore enable rapid, specific and sensitive onsite testing.

PMID- 17011182
TI  - Essential and expendable features of the circadian timekeeping mechanism.
AB  - Circadian clocks control behavioral, physiological and metabolic rhythms via one
      or more transcriptional feedback loops. In animals, two conserved feedback loops
      are thought to keep circadian time by mediating rhythmic transcription in
      opposite phases of the circadian cycle. Recent work in cyanobacteria nevertheless
      demonstrates that rhythmic transcription is dispensable for circadian
      timekeeping, raising the possibility that some features of the transcriptional
      feedback loops in animals are also expendable. Indeed, one of the two feedback
      loops is not necessary for circadian timekeeping in animals, but rhythmic
      transcription and post-translational modifications are both essential for keeping
      circadian time. These results not only confirm additional requirements within the
      animal circadian timekeeping mechanism, but also raise important questions about
      the function of conserved, yet expendable, features of the circadian timekeeping
      mechanism in animals.

PMID- 17011181
TI  - The role of acetylcholine in learning and memory.
AB  - Pharmacological data clearly indicate that both muscarinic and nicotinic
      acetylcholine receptors have a role in the encoding of new memories. Localized
      lesions and antagonist infusions demonstrate the anatomical locus of these
      cholinergic effects, and computational modeling links the function of cholinergic
      modulation to specific cellular effects within these regions. Acetylcholine has
      been shown to increase the strength of afferent input relative to feedback, to
      contribute to theta rhythm oscillations, activate intrinsic mechanisms for
      persistent spiking, and increase the modification of synapses. These effects
      might enhance different types of encoding in different cortical structures. In
      particular, the effects in entorhinal and perirhinal cortex and hippocampus might
      be important for encoding new episodic memories.

PMID- 17011183
TI  - Structural insights into dioxygen-activating copper enzymes.
AB  - Copper-containing enzymes that react with O(2) play a key role in many biological
      processes. Mononuclear, dinuclear and trinuclear copper centers function in O(2)
      binding, activation and subsequent substrate oxidation. Recent advances in the
      structural biology of O(2)-activating copper enzymes range from the
      identification of novel copper centers, such as that of particulate methane
      monooxygenase, to the elucidation of the details of O(2) binding and reactivity
      in peptidylglycine alpha-hydroxylating monooxygenase. Structures of phenoxazinone
      synthase and Fet3 contribute to our understanding of multicopper oxidases.
      Additionally, details of the tyrosinase structure provide new insight into how
      dicopper sites confer substrate specificity. A common theme for each of these
      enzymes is that the protein scaffold plays a major role in dictating the overall
      function.

PMID- 17011184
TI  - Patient preference for oral or intravenous chemotherapy: a randomised cross-over
      trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with
      colorectal cancer.
AB  - Until recently, fluorouracil (F) and leucovorin (L) had been considered the
      standard therapy for patients with colorectal cancer. However, several studies
      have shown that oral therapy with UFT/L or capecitabine is as effective as
      intravenous (i.v.) therapy and in addition it is claimed that patients prefer
      oral to i.v. therapy as long as efficacy is not compromised. In a previous
      crossover study by Borner et al., it was shown that 26 out of 31 patients
      preferred oral therapy with UFT/L to i.v. FL (Mayo regimen) [Borner M, Schoffski
      P, de Wit R, et al. Patient preferences and pharmacokinetics of oral modulated
      UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial
      in advanced colorectal cancer. Eur J Cancer 2002;38:349-58]. The objective of the
      present study was to investigate patient preference between i.v. FL and oral
      capecitabine using the design described by Borner. The Nordic FL schedule is a
      bolus regimen with efficacy comparable to other i.v. regimens and at the same
      time a very tolerable and easy administered regimen. We randomised 60 patients
      with colorectal cancer (53 patients received adjuvant therapy and seven patients
      received palliative therapy) to start therapy with either oral capecitabine or
      Nordic bolus FL. After 6 weeks of therapy (two courses of capecitabine or three
      courses of Nordic FL) patients were crossed over to the other regimen. After
      having completed 12 weeks of therapy the patients (49 evaluable patients) were
      asked to choose one of the regimens for a further 12 weeks of therapy. Patients
      had more side-effect when treated with capecitabine and a total of 30 out of 49
      (61%) preferred the Nordic FL regimen and 19 (39%) preferred capecitabine. We
      conclude that patients prefer the regimen with less toxicity and that it is of
      minor importance whether the medication is administrated orally at home or i.v.
      at the hospital.

PMID- 17011185
TI  - Mutational analysis of beta-catenin and the RAS-RAF signalling pathway in early
      flat-type colorectal tumours.
AB  - Morphologically, early colorectal tumours can be divided into two groups,
      protruded-type and flat-type. However, little is known about genetic mechanisms
      of the latter. We investigated mutations of beta-catenin, KRAS, BRAF, and PIK3CA
      in 310 early colorectal tumours. beta-catenin mutation was detected in 7.1% of
      310 tumours. beta-catenin mutation was detected in a significantly higher
      percentage of flat-type tumours with depressed areas (4/17, 23.5%) than in other
      tumours (18/293, 6.1%; p=0.0246). KRAS, BRAF, and PIK3CA mutations were detected
      in 21.6%, 5.4%, and 1.0% of 310 tumours, respectively. Concomitant mutations of
      beta-catenin and KRAS or BRAF were detected in seven tumours. Mutation of at
      least one gene was detected in a significantly higher percentage of flat-type
      tumour tissues (75/193, 38.9%) than in protruded-type tumour tissues (25/117,
      21.4%; p=0.0014), and it was correlated significantly with size (p=0.0001). In
      conclusion, beta-catenin mutation seemed to play an important role in flat-type
      tumours, especially in those with depressed areas. The genetic abnormalities
      could arise and accumulate in the early stage of colorectal tumourigenesis, and
      seem to contribute to the development of flat-type tumour.

PMID- 17011186
TI  - Anthracycline-induced cardiotoxicity: comparison of recommendations for
      monitoring cardiac function during therapy in paediatric oncology trials.
AB  - The use of anthracyclines is limited by a dose-dependent cardiotoxicity (A-CT).
      The aim of this study was to gain insight in the currently available guidelines
      for monitoring cardiotoxicity during anthracycline therapy in children and in the
      monitoring recommendations currently used in European paediatric oncology trials.
      An extensive literature search to identify guidelines was performed and one
      guideline was identified. Twelve protocols including anthracycline therapy were
      evaluated. With regard to the minimally required diagnostic tests, parameters and
      definitions of A-CT most protocols roughly followed the guideline. However, both
      monitoring schedules and recommendations to prevent further cardiac damage in
      case A-CT was diagnosed varied widely between protocols and only a minority of
      the protocols followed the recommendations of the guideline. In conclusion,
      despite an existing guideline, there is a wide variation in the recommendations
      for monitoring cardiac function during anthracycline therapy in the currently
      used European paediatric oncology protocols. A possible explanation could be the
      lack of rigorous evidence on the most optimal way to monitor cardiac function in
      children treated with anthracyclines. There is a strong need for evidence from
      clinical research which can support recommendations for monitoring cardiac
      function during anthracycline therapy for childhood cancer. In the meantime, it
      is important to standardize the used cardiac monitoring schedules.

PMID- 17011187
TI  - Binding of f-PIP, a pyrrole- and imidazole-containing triamide, to the inverted
      CCAAT box-2 of the topoisomerase IIalpha promoter and modulation of gene
      expression in cells.
AB  - An N-formamido pyrrole- and imidazole-containing triamide (f-PIP) has been shown
      by DNase I footprinting, SPR, and CD studies to bind as a stacked dimer to its
      cognate sequences: 5'-TACGAT-3' (5'-flank of the inverted CCAAT box-2 of the
      human topoisomerase IIalpha promoter) and 5'-ATCGAT-3'. A gel shift experiment
      provided evidence for f-PIP to inhibit protein-DNA interaction at the ICB2 site.
      Western blot studies showed that expression of the topoisomerase IIalpha gene in
      confluent NIH 3T3 cells was induced by treatment with f-PIP. The results
      suggested that the triamide was able to enter the nucleus, interacted with the
      target site within ICB2, inhibited NF-Y binding, and activated gene expression.

PMID- 17011188
TI  - Novel nucleotide triphosphates as potent P2Y2 agonists.
AB  - The synthesis and P2Y2 activities of a novel series of nucleoside triphosphates
      are described. Many of these compounds were potent agonists of the P2Y2 receptor.

PMID- 17011189
TI  - In silico identification and biochemical characterization of novel inhibitors of
      NQO1.
AB  - From in silico docking and COMPARE analysis, novel inhibitors of human NAD(P)H
      quinone oxidoreductase (NQO1) have been identified from the NCI compound
      database, the most potent of which has an observed IC(50) of 0.7muM. The
      inhibitors exhibit a diverse range of scaffolds. The ability of docking
      calculations to predict experimentally determined binding affinities for NQO1 is
      discussed, considering the influence of target flexibility and scoring function.

PMID- 17011190
TI  - The art of nursing: a hidden science?

PMID- 17011191
TI  - Fast Track: one hospital's journey.
AB  - This paper is the first of two articles discussing the implementation and
      evaluation of an innovative Fast Track process. This current paper explains how
      one metropolitan hospital identified the need to establish Fast Track in their
      Emergency Department and the journey that was taken to implement the initiative.
      The other paper presents the findings of the evaluation of the Fast Track process
      over a twelve month time frame. Fast Track is the treatment of minor injuries and
      illnesses by designated clinicians within the Emergency Department. The model was
      based upon the available literature from studies on Fast Track and "See and
      Treat" conducted in the United Kingdom, North America and Australia, and was
      adapted to address the type of presentations arriving at the hospital's Emergency
      Department. The initial change management process lasted twelve months and as a
      result Fast Track has revolutionised the way many patients are treated in the
      Emergency Department. Furthermore, Fast Track has provided nurses with the
      opportunity to achieve advanced skills in the areas of suturing and plastering.

PMID- 17011192
TI  - On the expression of joint moments during gait.
AB  - The purpose of the current study was to examine the effect of different reference
      frames on lower limb joint moments during gait with a view to identifying a
      recommended convention for clinical purposes. Data were collected from 10
      subjects (nine able-bodied adults and one child with diplegic cerebral palsy)
      whilst walking at a self-selected speed. Calculations utilised a three
      dimensional inverse dynamics model. For each joint, moments were expressed in
      four different reference frames. Three of the frames were orthogonal: laboratory
      frame; anatomical frame of proximal segment; anatomical frame of distal segment.
      The fourth reference frame was a non-orthogonal joint coordinate system (JCS).
      Significant differences in the joint moment profiles during gait were found with
      alternative references frames. This was apparent primarily for the transverse
      plane joint moments for able-bodied adult gait. For the pathological gait pattern
      presented, there were also marked differences in the frontal plane joint moments
      and more subtle ones in the sagittal plane. Whilst it is recognised that all
      possible reference frames for the expression of the net moment vector are
      mathematically valid, a decision needs to be made as to which one is more
      clinically useful. It is proposed that the non-orthogonal JCS is most logical on
      the basis of what, biomechanically, the joint moment actually represents.

PMID- 17011193
TI  - Functional outcome following modified Elmslie-Trillat procedure.
AB  - The aim of this study was to evaluate the mid- and long-term outcome of the
      modified Elmslie-Trillat procedure, as well as to detect factors affecting it.
      Thirty-eight patients (44 procedures) with a mean age of 31 years were included
      in this study. The reason for operation was patellar instability in 10 cases,
      anterior knee pain with malalignment of the extensor mechanism in 15 cases and a
      combination of both in 19 cases. Patients were followed for an average of 40
      months (range=18-130 months). The functional outcome was very satisfactory or
      satisfactory for 73% of patients. According to Cox's criteria it was excellent in
      13 cases (30%), good in 18 (41%), fair in 7 (16%) and poor in the remaining 6
      (13%). Patients scored an average of 3.5 (range=2-8) in their Tegner Activity
      Scale, while their score in Activities of Daily Living Scale of the Knee Outcome
      Survey ranged from 43 to 98 (average=76). Result analysis revealed a better
      functional outcome when the operation was performed for patellar instability, as
      well as in the absence of grade 3 or 4 chondral changes in the patellofemoral
      joint at the time of operation. Elmslie-Trillat procedure satisfactorily restores
      patellofemoral stability and offers a very good functional outcome, especially in
      the absence of significant chondral changes in the patellofemoral joint at the
      time of operation.

PMID- 17011194
TI  - Increased joint loads during walking--a consequence of pain relief in knee
      osteoarthritis.
AB  - Joint pain is a primary symptom in knee osteoarthritis (OA), but the effect of
      pain and pain relief on the knee joint mechanics of walking is not clear. In this
      study, the effects of local knee joint analgesia on knee joint loads during
      walking were studied in a group of knee osteoarthritis patients. A group of
      healthy subjects was included as a reference group. The joint loads were
      calculated from standard gait analysis data obtained with standardised walking
      speed (4 km/h). The gait analyses were performed before and after pain relief by
      intra-articular injections of 10 mL lidocaine (1%). Pre-injection measurements
      revealed lower joint loads in the OA group compared to the reference group.
      Following injections pain during walking decreased significantly and the joint
      loads increased in the OA group during the late single support phase to a level
      comparable to the reference group. Although the patients walked with less
      compressive knee joint forces compared to the reference group, the effects of
      pain relief may accelerate the degenerative changes.

PMID- 17011195
TI  - Knee skin temperature following uncomplicated total knee replacement.
AB  - This prospective study aimed to establish the pattern of knee skin temperature
      following uncomplicated primary total knee replacement. Thirty-two patients were
      included. The skin temperature of operated and contralateral knees was measured
      preoperatively and daily during the first 6 weeks postoperatively. Measurements
      were also taken at 3, 6, 12 and 24 months following surgery. The difference in
      temperature between the two knees had a mean value of (+)2.9 degrees C at 7 days.
      This mean value decreased to (+)1.6 degrees C at 6 weeks, (+)1.3 degrees C at 3
      months, (+)0.9 degrees C at 6 months (+)0.3 degrees C at 12 months and (+)0.0
      degrees C at 24 months. Following uncomplicated total knee replacement, the
      operated knee skin temperature increases compared to the contralateral knee. The
      difference decreases gradually but remains statistically significant up to at
      least 6 months following surgery. In the absence of other features of infection,
      local knee warmth should not cause concern.

PMID- 17011196
TI  - Synthesis and biological evaluation of novel pyrrolopyrrolizinones as anticancer
      agents.
AB  - We herein describe the synthesis of novel 3-(het)aryl-pyrrolo[2,3-b]pyrrolizin
      8(1H)-ones starting from commercial (het)aryl-acetonitriles. A more convergent
      route was also described through the first synthesis of ethyl 3-amino-4-bromo-1H
      pyrrole-2-carboxylate 17. The antiproliferative activities of these compounds
      were tested toward various cell lines and one of them 10k shows interesting
      cytotoxic properties, although it was less potent than our lead compound in
      thiophene series 1k.

PMID- 17011197
TI  - Antioxidant properties of violacein: possible relation on its biological
      function.
AB  - Violacein, a violet pigment produced by Chromobacterium violaceum, has attracted
      much attention in recent literature due to its pharmacological properties. In
      this work, the antioxidant properties of violacein were investigated. The
      reactivity with oxygen and nitrogen reactive species and 1,1-diphenyl-2-picryl
      hydrazyl (DPPH), a stable free radical, was evaluated. EPR studies were carried
      out to evaluate the reactivity with the hydroxyl radical. The action of violacein
      against lipid peroxidation in three models of lipid membranes, including rat
      liver microsomes, Egg and Soy bean phosphathidylcholine liposomes were also
      evaluated. The compound reacted with DPPH (IC(50)=30microM), nitric oxide
      (IC(50)=21microM), superoxide radicals (IC(50)=125microM) and decreased the
      hydroxyl radical EPR signal. The compound protected the studied membranes against
      peroxidation induced by reactive species in the micromolar range. The
      reconstitution of violacein into the membranes increased its antioxidant effect.
      These results indicate that the compound has strong antioxidant potential. Based
      on these results we suggest violacein plays an important role with the
      microorganism membrane in defense against oxidative stress.

PMID- 17011198
TI  - Two-dimensional agnor evaluation as a prognostic variable in urinary bladder
      carcinoma: a different approach via total agnor area/nucleus area per cell.
AB  - Traditional criterions are not sufficient to predict accurately the recurrence of
      transitional cell carcinoma of the urinary bladder. Therefore, we aimed to
      evaluate the AgNORs via total AgNOR area/nucleus area (TAA/NA) for each cell as a
      prognostic parameter, in TCC of urinary bladder. Tumor tissues of 20 consecutive
      cases of male bladder cancer patients were divided into two groups as middle
      differentiated (LG) and high grade (HG). The extra-tumoral tissue (ETT) samples
      of 10 males served as control group. A second control group (HC) consisted of
      five healthy and normal bladder tissue samples. The 3 microm of sections from
      each paraffin embedded tumoral, extra-tumoral and normal tissue samples served as
      patient and control groups. After deparaffinization and rehydratation steps,
      silver (AgNO(3)) staining of nucleolar organizer regions-associated proteins
      (AgNORs) was performed. Instead of Giemsa stain, we used Hematoxylin for contra
      staining. The images of the 100 analyzable nuclei from each tissue sample,
      transferred by means of a video camera and video capture card from microscope and
      recorded onto a computer. Software was prepared in Delphi language for analysis.
      Mean (E+02) TAA/NA values of HC, ETT, LG and HG groups were 6.97+2.80, 5.70+1.82,
      7.80+3.22 and 9.24+3.88, respectively. Statistical comparisons have shown
      significant differences between all groups. In conclusion, mean TAA/NA per cell
      has a potential to be a prognostic parameter. Therefore, further evaluation of
      big patient series will be useful.

PMID- 17011199
TI  - Low-magnesium uranium-calcite with high degree of crystallinity and gigantic
      luminescence emission.
AB  - Cabrera (Madrid) low-Mg calcites exhibit: (i) an unusual twofold elevation in X
      ray diffraction pattern intensity; (ii) a 60-fold elevation of luminescence
      emission, compared to six common natural calcites selected for comparison
      purposes; (iii) a natural relatively high radiation level of circa 200 nSvh(-1)
      not detected in 1300 other calcites from the Natural History Museum of Madrid.
      Calcites were analysed by the X-ray diffraction powder method (XRD), cathodo
      luminescence spectroscopy in scanning electron microscopy (CL-SEM),
      thermoluminescence (TL), differential thermal analysis (DTA), X-ray fluorescence
      spectrometry (XRF) and particle size distribution (PSD). The Cabrera calcite
      study shows: (i) helicoidally distributed steps along the (0001) orientation;
      (ii) protuberance defects onto the (0001) surface, observed by SEM; (iii) XRF
      chemical contents of 0.03% MgO, 0.013% of Y(2)O(3), and 0.022% of U(3)O(8), with
      accessory amounts of rare earth elements (REE); (iv) DTA dissociation temperature
      of 879 degrees C; (v) TL maxima peaks at 233 and 297 degrees C whose areas are 60
      times compared to other calcites; (vi) spectra CL-SEM bands at 2.0 and 3.4 eV in
      the classic structure of Mn(2+) activators; (vii) a twofold XRD pattern explained
      given that sample is a low-Mg calcite. The huge TL and CL emissions of the
      Cabrera calcite sample must be linked with the uranyl group presence. This
      intense XRD pattern in low-Mg calcites could bring into being analytical errors.

PMID- 17011200
TI  - Preparation and characterization of 99mTc(CO)3-BPy-RGD complex as alphav beta3
      integrin receptor-targeted imaging agent.
AB  - The aim of this study is to develop a novel arginine-glycine-aspartic acid (RGD)
      peptide-containing ligand for (99m)Tc labeling as alpha(v)beta(3) integrin
      receptor-targeted imaging agent. BPy-RGD conjugate was successfully synthesized
      by coupling of 5-carboxylate-2,2'-bipyridine and c(RGDyK) peptide through
      EDC/SNHS in aqueous solution and was characterized by MADLI-TOF-MS (m/z=802.72,
      C(38)H(48)N(11)O(9)). (99m)Tc(CO)(3)-BPy-RGD was prepared by exchange reaction
      between [(99m)Tc(H(2)O)(3)(CO)(3)](+) and BPy-RGD. Final product was purified by
      HPLC and tested for octanol/water partition coefficient. Cell-binding assays of
      BPy-RGD and unmodified c(RGDyK) were tested in MDA-MB-435 cells ((125)I
      echistatin as radioligand). Preliminary biodistribution of the (99m)Tc(I)-labeled
      radiotracer in orthotopic MDA-MB-435 breast tumor xenograft model was also
      evaluated. The BPy-RGD conjugate had good integrin-binding affinity (50%
      inhibitory concentration (IC(50))=92.51+/-22.69 nM), slightly lower than
      unmodified c(RGDyK) (IC(50)=59.07+/-11.03 nM). The hydrophilic radiotracer also
      had receptor-mediated activity accumulation in MDA-MB-435 tumor (1.45+/-0.25
      percentage of injected dose per gram (%ID/g) at 1.5h postinjection (p.i.)), which
      is known to be integrin positive. After blocking with c(RGDyK), the tumor uptake
      was reduced from 0.71+/-0.01%ID/g to 0.33+/-0.18%ID/g at 4h p.i. (99m)Tc(I)
      tricarbonyl complex of cyclic RGD peptide is a promising strategy for integrin
      targeting. Further modification of the bipyridine-conjugated RGD peptide by using
      more potent RGD peptides and fine tuning of the tether group between the RGD
      moiety and (99m)Tc(CO)(3)(+) core to improve the tumor targeting efficacy and in
      vivo kinetic profiles is currently in progress.

PMID- 17011201
TI  - Progress in numerical modelling of the Cl influence on gamma-ray spectra from an
      n-gamma logging tool, by using the improved ENDF data for radiative capture.
AB  - Quality of the numerical modelling (MCNP code) of the spectrometric neutron-gamma
      benchmark experiment, performed at the Polish Calibration Station BGW in Zielona
      Gora for quantification of the main rock elements: Si, Ca, Fe and H, is
      considered. Elemental concentrations obtained from the measurements and
      simulations, for the rock models with water-filled boreholes, are in good
      agreement. For chlorine present in the borehole, the quality of the numerical
      reproducibility of the measured elemental concentrations depends on the cross
      section library used for the Cl(n,gamma)Cl reaction. The standard evaluated
      nuclear data library ENDF/B-VI Release 2 supplies imperfect data for photon
      production from thermal neutron capture in Cl. The improved cross sections for
      Cl(n,gamma)Cl are included in the ENDF/B-VI Release 8 library. Superiority of
      this new compilation over the previous one is shown in the paper. The accuracies
      for the Si, Ca and Fe determination have been improved by about 36%, 19.9% and
      21.4%, respectively, when the ENDF/B-VI Release 8 library has been used for Cl.

PMID- 17011202
TI  - Enhanced survival and regeneration of axotomized retinal neurons by repeated
      delivery of cell-permeable C3-like Rho antagonists.
AB  - Inactivation of Rho GTPase with a single intraocular injection of Rho antagonists
      stimulates survival and regeneration of retinal ganglion cells (RGCs) after optic
      nerve injury. However, this effect is short-lived. Here we tested the impact of
      multiple injections of C3-like Rho antagonists on RGC viability and axon
      regeneration after optic nerve lesion. Our data show that both neuronal survival
      and axon regeneration were enhanced with repeated delivery of cell-permeable C3.
      We found an approximately 1.5-fold increase in RCG survival when additional Rho
      antagonist injections were performed after the first week from the time of
      lesion. In contrast, increased regeneration required early inactivation of Rho
      and injections performed in the second week did not further enhance regenerative
      outcome. These results reveal differences in the length of the therapeutic
      windows through which Rho inactivation acts on RGC survival or regeneration after
      axotomy.

PMID- 17011203
TI  - The role of substantia nigra pars reticulata in modulating clonic seizures is
      determined by testosterone levels during the immediate postnatal period.
AB  - GABAergic activation of substantia nigra pars reticulata (SNR) at postnatal day
      (PN) 15 has sex-specific features on seizure control in vivo and
      electrophysiological responses in vitro. In males, the GABA(A)-receptor agonist
      muscimol has proconvulsant effects and induces depolarizing responses. In
      females, muscimol has no effect on seizures and evokes hyperpolarizing responses.
      We determined the time period during which sex hormones must be present to
      produce the sex-specific muscimol effects on seizures and their influence on SNR
      GABA(A) receptor-mediated postsynaptic currents. Exposure to testosterone or its
      metabolites (estrogen or dihydrotestosterone) during PN0-2 in females or males
      castrated at PN0 was sufficient to produce proconvulsant muscimol effects but did
      not affect the in vitro GABA responses, which remained hyperpolarizing. The data
      suggest that the PN0-2 period is critical for the development of the seizure
      controlling SNR system; the hormonal effect on seizure control is independent
      from their effect on GABA conductance.

PMID- 17011204
TI  - Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV
      neuropathology.
AB  - This study sought to determine the role of the transcription factor E2F1 in CXCR4
      mediated neurotoxicity and HIV neuropathology. We studied the effect of the HIV
      envelope protein gp120 on the expression of E2F1-dependent apoptotic proteins in
      human and rodent neurons and examined the expression pattern of E2F1 in the brain
      of HIV-infected individuals. Our findings suggest that in cultured neurons gp120
      increased E2F1 levels in the nucleus, stimulated its transcriptional activity and
      enhanced the expression of the E2F1 target proteins Cdc2 and Puma. Studies with
      neuronal cultures from E2F1 deficient mice demonstrated that the transcription
      factor is required for gp120-induced neurotoxicity and up-regulation of Cdc2 and
      Puma. Levels of E2F1 protein were greater in the nucleus of neurons in brains of
      HIV-infected patients exhibiting dementia when compared to HIV-negative subjects
      or HIV-positive neurologically normal patients. Overall, these studies indicate
      that E2F1 is primarily involved in CXCR4-mediated neurotoxicity and HIV
      neuropathogenesis.

PMID- 17011205
TI  - Oral uridine pro-drug PN401 is neuroprotective in the R6/2 and N171-82Q mouse
      models of Huntington's disease.
AB  - Previously, uridine pro-drug 2',3',5'-tri-O-acetyluridine (PN401) was shown to be
      protective in the mitochondrial complex II inhibitor 3-nitropropionic acid model
      of Huntington's disease (HD). In this study, PN401 increased survival and
      improved motor function on the rotarod in both R6/2 and N171-82Q polyglutamine
      repeat mouse models of HD. PN401 significantly decreased neurodegeneration in
      both the piriform cortex and striatum although PN401 decreased huntingtin protein
      aggregates only in the striatum. Cortical and striatal brain-derived neurotrophic
      factor (BDNF) protein levels were reduced in the +/- compared to the -/- N171-82Q
      mice and PN401 treatment significantly increased cortical BDNF in both +/- and -/
      mice, but PN401 did not affect striatal BDNF. These results suggest that PN401
      may have beneficial effects in the treatment of neurodegenerative diseases such
      as HD.

PMID- 17011206
TI  - Evidence that intracellular cyclophilin A and cyclophilin A/CD147 receptor
      mediated ERK1/2 signalling can protect neurons against in vitro oxidative and
      ischemic injury.
AB  - We previously reported that cyclophilin A protein is up-regulated in cortical
      neuronal cultures following several preconditioning treatments. In the present
      study, we have demonstrated that adenoviral-mediated over-expression of
      cyclophilin A in rat cortical neuronal cultures can protect neurons from
      oxidative stress (induced by cumene hydroperoxide) and in vitro ischemia (induced
      by oxygen glucose deprivation). We subsequently demonstrated that cultured
      neurons, but not astrocytes, express the recently identified putative cyclophilin
      A receptor, CD147 (also called neurothelin, basigin and EMMPRIN), and that
      administration of purified cyclophilin A protein to neuronal cultures induces a
      rapid but transient phosphorylation of the extracellular signal-regulated kinase
      (ERK) 1/2. Furthermore, administration of purified cyclophilin A protein to
      neuronal cultures protects neurons from oxidative stress and in vitro ischemia.
      Interestingly, we detected up-regulation of cyclophilin A mRNA, but not protein
      in the hippocampus following a 3-min period of sublethal global cerebral ischemia
      in the rat. Despite our in vivo findings, our in vitro data show that cyclophilin
      A has both intracellular- and extracellular-mediated neuroprotective mechanisms.
      To this end, we propose cyclophilin A's extracellular-mediated neuroprotection
      occurs via CD147 receptor signalling, possibly by activation of ERK1/2 pro
      survival pathways. Further characterization of cyclophilin A's neuroprotective
      mechanisms may aid the development of a neuroprotective therapy.

PMID- 17011207
TI  - Investigation via ion pore transplantation of the putative relationship between
      glutamate receptors and K+ channels.
AB  - The pore domains of ionotropic glutamate receptors (iGluRs) and potassium
      channels (K(+) channels) show several structural similarities. To test for
      functional compatibility, we transferred pore regions from prokaryotic,
      invertebrate, and vertebrate K(+) channels into pharmacologically representative
      iGluRs and vice versa. Although the chimeric proteins were expressed on the cell
      surface, only one of 45 pore chimeras showed ion channel function: The kainate
      receptor subunit GluR6, carrying the pore loop plus adjacent transmembrane
      domains of the prokaryotic, glutamate-gated, K(+)-selective GluR0, adopted
      several electrophysiological properties of the donor pore upon pore
      transplantation. This suggests that, despite structural similarities between
      iGluR and K(+) channel pores, there is a lack of functional compatibility so that
      K(+) channel pores cannot be gated by the iGluR gating machinery, and vice versa.
      However, K(+)-selective pores can be gated in an iGluR sequence environment,
      given a similar signal transduction mechanism as appears to be present in GluR0.

PMID- 17011208
TI  - LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal
      cord injury.
AB  - LINGO-1 is a CNS-specific protein and a functional component of the
      NgR1/p75/LINGO-1 and NgR1/TAJ(TROY)/LINGO-1 signaling complexes that mediate
      inhibition of axonal outgrowth. These receptor complexes mediate the axonal
      growth inhibitory effects of Nogo, myelin-associated glycoprotein (MAG) and
      oligodendrocyte-myelin glycoprotein (OMgp) via RhoA activation. Soluble LINGO-1
      (LINGO-1-Fc), which acts as an antagonist of these pathways by blocking LINGO-1
      binding to NgR1, was administered to rats after dorsal or lateral hemisection of
      the spinal cord. LINGO-1-Fc treatment significantly improved functional recovery,
      promoted axonal sprouting and decreased RhoA activation and increased
      oligodendrocyte and neuronal survival after either rubrospinal or corticospinal
      tract transection. These experiments demonstrate an important role for LINGO-1 in
      modulating axonal outgrowth in vivo and that treatment with LINGO-1-Fc can
      significantly enhance recovery after spinal cord injury.

PMID- 17011209
TI  - Cloning, expression and characterization of metallothionein from the Antarctic
      clam Laternula elliptica.
AB  - The genes for two apparent subtypes of metallothionein (MT) isoform were isolated
      from the Antarctic clam Laternula elliptica. Determination of the nucleotide
      sequence showed that the gene consists of 222 bp that code a 73-amino acid
      protein. The comparison between MT cDNA sequences of L. elliptica and other
      bivalves showed strong homologies on positions of cysteine residues, which are
      important for their metal binding abilities. The gene for the MT was inserted
      into a pET vector and overexpressed as a carboxyl terminal extension of
      glutathionein-S-transferase (GST) in Escherichia coli. After the GST fusion
      proteins had been purified by glutathione-Sepharose affinity chromatography
      column and digested with enterokinase, the MT was purified with gel filtration
      and analyzed for its biochemical properties. Recombinant MTs were reconstituted
      with Cd, Cu, and Zn, and kinetic studies of the reactions with electrophilic
      disulphide, DTNB, were investigated to explore their metal binding ability. It is
      revealed that the Cd-MT and Zn-MT react with DTNB biphasically, and that Zn-MT
      reacts with DTNB more rapidly, and with a significantly greater pseudo-first
      order rate constant. Cu-MT reacts monophasically and releases metal slowly from
      MT.

PMID- 17011210
TI  - Secretory expression of synthetic human Fas ligand extracellular domain gene in
      Pichia pastoris: influences of tag addition and N-glycosylation site deletion,
      and development of a purification method.
AB  - Human Fas ligand is a medically important membrane glycoprotein that induces the
      apoptosis of harmful cells. A new secretory expression and purification method
      was devised for the production of a large amount of recombinant human Fas ligand
      extracellular domain (hFasLECD) by Pichia pastoris. The expression plasmid
      containing a synthetic hFasLECD gene designed using yeast optimal codons was
      constructed for the secretion of hFasLECD. The secreted product exhibited the
      specific binding activity toward soluble human Fas receptor extracellular domain
      human IgG(1)-Fc domain fusion protein, and the receptor-ligand complex was
      immunoprecipitated by Protein A conjugated agarose-gel beads. The influences of
      the N- and C- terminal addition of FLAG/(His)(6) tag spaced by pentaglycine
      sequence and the sequentially accumulative deletions of N-glycosylation sites
      within hFasLECD were investigated. The secretion of functional hFasLECD was
      retained after the N-terminal tagging and the deletion of either single or double
      N-glycosylation sites. As judged from SDS-PAGE analysis of the culture
      supernatant, the N-terminal addition of FLAG-(Gly)(5) tag and the deletion of
      single N-glycosylation site via N184Q mutation increased the secretion level of
      the product. In contrast, the C-terminal tagged genes and all N-glycosylation
      sites deleted gene failed to direct the secretion of functional hFasLECD. The
      secreted products in the culture medium were purified using a cation-exchange
      chromatography and a gel-filtration chromatography. The purified hFasLECDs
      existed as trimers composed of a mixture of monomer species in different
      glycosylation states. Approximately five milligram of functional N-terminal FLAG
      (Gly)(5) tagged hFasLECD N184Q mutant was obtained from one liter culture
      supernatant.

PMID- 17011211
TI  - Bsoft: image processing and molecular modeling for electron microscopy.
AB  - Bsoft is a software package written for image processing of electron micrographs,
      interpretation of reconstructions, molecular modeling, and general image
      processing. The code is modularized to allow for rapid testing and deployment of
      new processing algorithms, while also providing sufficient infrastructure to deal
      with many file formats and parametric data. The design is deliberately open to
      allow interchange of information with other image and molecular processing
      software through a standard parameter file (currently a text-based encoding of
      parameters in the STAR format) and its support of multiple image and molecular
      formats. It also allows shell scripting of processes and allows subtasks to be
      distributed across multiple computers for concurrent processing. Bsoft has
      undergone many modifications and advancements since its initial release [Heymann,
      J.B., 2001. Bsoft: image and molecular processing in electron microscopy. J.
      Struct. Biol. 133, 156-169]. Much of the emphasis is on single particle analysis
      and tomography, and sufficient functionality is available in the package to
      support most needed operations for these techniques. The key graphical user
      interface is the program bshow, which displays an image and is used for many
      interactive purposes such as fitting the contrast transfer function or picking
      particles. Bsoft also offers various tools to manipulate atomic structures and to
      refine the fit of a known molecular structure to a density in a reconstruction.

PMID- 17011212
TI  - Orienting attention to semantic categories.
AB  - We investigated the ability to orient attention to a complex, non-perceptual
      attribute of stimuli-semantic category. Behavioral consequences and neural
      correlates of semantic orienting were revealed and compared with those of spatial
      orienting, using event-related functional magnetic-resonance imaging. Semantic
      orienting significantly shortened response times to identify word stimuli,
      showing that it is possible to focus attention on non-perceptual attributes of
      stimuli to enhance behavioral performance. Semantic-orienting cues engaged
      parietal and frontal areas that were also involved in spatial orienting, but in
      addition engaged brain areas associated with semantic analysis of words, such as
      the left anterior inferior frontal cortex. These findings show that attentional
      orienting selectively engages brain areas with functional specialization for the
      predicted attributes. They also support the existence of a core frontoparietal
      network, which controls attentional orienting in speeded response tasks
      independently of the type of expectations, interacting with task-relevant
      functionally specialized areas to optimize perception and action.

PMID- 17011213
TI  - Laminar profiles of functional activity in the human brain.
AB  - Functional magnetic resonance imaging (fMRI) data were obtained in human visual
      cortex using sub-millimeter voxels at a field strength of 3 T. Reliable
      functional signals were largely confined to the gray matter and these responses
      measure the retinotopic organization of visual cortex. Functional signals were
      further characterized with respect to their laminar position within the cortical
      gray matter. The laminar response profiles during our visuospatial attention
      task, normalized for cortical thickness, had a stereotypical shape, with a peak
      in the superficial gray matter and declining in the deeper layers. The thickness
      of the sheet producing functional signals was in excellent agreement with the
      estimated structural thickness of the gray matter throughout early visual cortex
      (error < 0.5 mm). Thickness measurements were highly repeatable from session-to
      session (error < 0.4 mm). Hence, it is feasible and useful to use high-resolution
      fMRI to measure laminar activity profiles. The ability to distinguish signals
      arising in different lamina has significant potential scientific and clinical
      applications.

PMID- 17011214
TI  - An adaptive filter for suppression of cardiac and respiratory noise in MRI time
      series data.
AB  - The quality of MRI time series data, which allows the study of dynamic processes,
      is often affected by confounding sources of signal fluctuation, including the
      cardiac and respiratory cycle. An adaptive filter is described, reducing these
      signal fluctuations as long as they are repetitive and their timing is known. The
      filter, applied in image domain, does not require temporal oversampling of the
      artifact-related fluctuations. Performance is demonstrated for suppression of
      cardiac and respiratory artifacts in 10-minute brain scans on 6 normal
      volunteers. Experimental parameters resemble a typical fMRI experiment (17
      slices; 1700 ms TR). A second dataset was acquired at a rate well above the
      Nyquist frequency for both cardiac and respiratory cycle (single slice; 100 ms
      TR), allowing identification of artifacts specific to the cardiac and respiratory
      cycles, aiding assessment of filtering performance. Results show significant
      reduction in temporal standard deviation (SD(t)) in all subjects. For all 6
      datasets with 1700 ms TR combined, the filtering method resulted in an average
      reduction in SD(t) of 9.2% in 2046 voxels substantially affected by respiratory
      artifacts, and 12.5% for the 864 voxels containing substantial cardiac artifacts.
      The maximal SD(t) reduction achieved was 52.7% for respiratory and 55.3% for
      cardiac filtering. Performance was found to be at least equivalent to the
      previously published RETROICOR method. Furthermore, the interaction between the
      filter and fMRI activity detection was investigated using Monte Carlo
      simulations, demonstrating that filtering algorithms introduce a systematic error
      in the detected BOLD-related signal change if applied sequentially. It is
      demonstrated that this can be overcome by combining physiological artifact
      filtering and detection of BOLD-related signal changes simultaneously. Visual
      fMRI data from 6 volunteers were analyzed with and without the filter proposed
      here. Inclusion of the cardio-respiratory regressors in the design matrix yielded
      a 4.6% t-score increase and 4.0% increase in the number of significantly
      activated voxels.

PMID- 17011215
TI  - Interaction between a verbal working memory network and the medial temporal lobe.
AB  - The irrelevant speech effect illustrates that sounds that are irrelevant to a
      visually presented short-term memory task still interfere with neuronal function.
      In the present study we explore the functional and effective connectivity of such
      interference. The functional connectivity analysis suggested an interaction
      between the level of irrelevant speech and the correlation between in particular
      the left superior temporal region, associated with verbal working memory, and the
      left medial temporal lobe. Based on this psycho-physiological interaction, and to
      broaden the understanding of this result, we performed a network analysis, using
      a simple network model for verbal working memory, to analyze its interaction with
      the medial temporal lobe memory system. The results showed dissociations in terms
      of network interactions between frontal as well as parietal and temporal areas in
      relation to the medial temporal lobe. The results of the present study suggest
      that a transition from phonological loop processing towards an engagement of
      episodic processing might take place during the processing of interfering
      irrelevant sounds. We speculate that, in response to the irrelevant sounds, this
      reflects a dynamic shift in processing as suggested by a closer interaction
      between a verbal working memory system and the medial temporal lobe memory
      system.

PMID- 17011216
TI  - Outcomes after arthroscopic rotator cuff repairs.
AB  - Recently, advances in arthroscopic techniques have allowed shoulder surgeons to
      perform fully arthroscopic repair of full-thickness tears. Outcome data have
      shown that improvement is inconsistent between studies. We performed a
      retrospective review of 105 consecutive patients who underwent arthroscopic
      rotator cuff repair from 1999 to 2002. Preoperative and postoperative evaluation
      consisted of a history, questionnaire, and examination to determine American
      Shoulder and Elbow Surgeons, Constant, and visual analog pain scores. Complete
      data were available for a minimum of 12 months (range, 12-45 months) for 71
      patients. Increases in range of motion and outcome scores and associated
      reductions in visual analog scores were all significant. With massive tears,
      scores and pain were significantly improved. Arthroscopic rotator cuff repair
      reliably improves functional deficits and pain regardless of tear size. Smaller
      tears yield significant improvement in American Shoulder and Elbow Surgeons,
      Constant, and pain scores. Functional improvement was seen with massive tears,
      but gains in strength and motion were less dramatic.

PMID- 17011217
TI  - The costs of epilepsy misdiagnosis in England and Wales.
AB  - BACKGROUND: The management of epilepsy incurs significant costs to the United
      Kingdom (UK) National Health Service (NHS). Making a diagnosis of epilepsy can,
      however, be difficult and misdiagnosis frequently occurs when patients are seen
      by non-specialists. This study estimates the financial costs of epilepsy
      misdiagnosis in the NHS in England and Wales. METHODS: Standard costing methods
      were applied to estimate the costs attributable to epilepsy misdiagnosis. The
      primary data were published in UK studies on the prevalence of epilepsy, epilepsy
      misdiagnosis and costs identified from Medline, Cinahl and Embase (1996-May
      2006). RESULTS: An estimated total of 92,000 people were misdiagnosed with
      epilepsy in England and Wales in 2002. The average medical cost per patient per
      year of misdiagnosis was 316 pounds sterling, with the chief economic burdens
      being inpatient admissions (45%), inappropriate prescribing of antiepileptic
      drugs (AEDs) (26%), outpatient attendances (16%) and general practitioner (GP)
      care (8%). The estimated annual medical costs in England and Wales were
      29,000,000 pounds sterling, while total costs could reach up to 138,000,000
      pounds sterling a year. CONCLUSIONS: Allowing for uncertainty, and considering
      the analysis exclusively from the NHS/CBS (community based services) perspective
      the opportunity costs of misdiagnosis are substantial. There is a need for health
      care commissioners to ensure that misdiagnosis is kept to a minimum by ensuring
      that individuals with a recent onset suspected seizure are seen as soon as
      possible by a specialist medical practitioner with training and expertise in
      epilepsy.

PMID- 17011218
TI  - Establishment of a mouse primary co-culture of endometrial epithelial cells and
      peripheral blood leukocytes: effect on epithelial barrier function and leukocyte
      survival.
AB  - This study aimed to establish an in vitro co-culture model that would allow us to
      study the interaction between endometrial epithelial cells and immune cells. Flow
      cytometry analysis and cell surface marker staining were used to identify
      suitable immune leukocytes from a range of sources, such as intraepithelial
      lymphocytes (IEL), thymocytes, splenocytes and peripheral blood leukocytes.
      Optimizing culture conditions such as cell viabilities, cell seeding ratios and
      densities and co-culture methods were examined and determined. Results showed
      that co-culture of mouse endometrial epithelial cells (EEC) with peripheral blood
      leukocytes (PBL) at seeding densities of 3.0 x 10(6) and 1.0 x 10(6)cells/ml,
      respectively, appeared to affect both the survival of leukocytes and epithelial
      barrier function. Cell viability counts of immune cells showed 95% and 72.5% cell
      survival after isolation and after 4 days in co-culture with EEC, respectively,
      but only 11% cell survival when cultured alone for 4 days without EEC. Short
      circuit current (I(sc)) results also showed that EEC and PBL co-culture exhibited
      a four-fold increase in the transepithelial resistance (TER) as compared to EEC
      culture alone, indicating enhanced protective barrier function. Taken together,
      the currently established in vitro co-culture model of endometrial epithelial
      cells and immune cells may provide a means to investigate local cellular immune
      responses upon uterine infections.

PMID- 17011219
TI  - Combined passive and active shimming for in vivo MR spectroscopy at high magnetic
      fields.
AB  - The use of high magnetic fields increases the sensitivity and spectral dispersion
      in magnetic resonance spectroscopy (MRS) of brain metabolites. Practical
      limitations arise, however, from susceptibility-induced field distortions, which
      are increased at higher magnetic field strengths. Solutions to this problem
      include optimized shimming, provided that active, i.e., electronic, shimming can
      operate over a sufficient range. To meet our shim requirements, which were an
      order of magnitude greater than the active shim capacity of our 7T MR system, we
      developed a combined passive and active shim approach. Simple geometries of
      ferromagnetic shim elements were derived and numerically optimized to generate a
      complete set of second-order spherical harmonic shim functions in a modular
      manner. The major goals of the shim design were maximization of shim field
      accuracy and ease of practical implementation. The theoretically optimized ferro
      shim geometries were mounted on a cylindrical surface and placed inside the
      magnet bore, surrounding the subject's head and the RF coil. Passive shimming
      generated very strong shim fields and eliminated the worst of the field
      distortions, after which the field was further optimized by flexible and highly
      accurate active shimming. Here, the passive-shimming procedure was first
      evaluated theoretically, then applied in phantom studies and subsequently
      validated for in vivo 1H MRS in the macaque visual cortex. No artifacts due to
      the passive shim setup were observed; adjustments were reproducible between
      sessions. The modularity and the reduction to two pieces per shim term in this
      study is an important simplification that makes the method applicable also for
      passive shimming within single sessions. The feasibility of very strong, flexible
      and high-quality shimming via a combined approach of passive and active shimming
      is of great practical relevance for MR imaging and spectroscopy at high field
      strengths where shim power is limited or where shimming of specific anatomical
      regions inherently requires strong shim fields.

PMID- 17011220
TI  - Weighted least-squares deconvolution method for discovery of group differences
      between complex biofluid 1H NMR spectra.
AB  - Biomarker discovery through analysis of high-throughput NMR data is a
      challenging, time-consuming process due to the requirement of sophisticated,
      dataset specific preprocessing techniques and the inherent complexity of the
      data. Here, we demonstrate the use of weighted, constrained least-squares for
      fitting a linear mixture of reference standard data to complex urine NMR spectra
      as an automated way of utilizing current assignment knowledge and the ability to
      deconvolve confounded spectral regions. Following the least-squares fit,
      univariate statistics were used to identify metabolites associated with group
      differences. This method was evaluated through applications on simulated datasets
      and a murine diabetes dataset. Furthermore, we examined the differential ability
      of various weighting metrics to correctly identify discriminative markers. Our
      findings suggest that the weighted least-squares approach is effective for
      identifying biochemical discriminators of varying physiological states.
      Additionally, the superiority of specific weighting metrics is demonstrated in
      particular datasets. An additional strength of this methodology is the ability
      for individual investigators to couple this analysis with laboratory specific
      preprocessing techniques.

PMID- 17011221
TI  - Hadamard NMR spectroscopy for two-dimensional quantum information processing and
      parallel search algorithms.
AB  - Hadamard spectroscopy has earlier been used to speed-up multi-dimensional NMR
      experiments. In this work, we speed-up the two-dimensional quantum computing
      scheme, by using Hadamard spectroscopy in the indirect dimension, resulting in a
      scheme which is faster and requires the Fourier transformation only in the direct
      dimension. Two and three qubit quantum gates are implemented with an extra
      observer qubit. We also use one-dimensional Hadamard spectroscopy for binary
      information storage by spatial encoding and implementation of a parallel search
      algorithm.

PMID- 17011222
TI  - Respiratory water loss during rest and flight in European Starlings (Sturnus
      vulgaris).
AB  - Respiratory water loss in Starlings (Sturnus vulgaris) at rest and during flight
      at ambient temperatures (T(amb)) between 6 and 25 degrees C was calculated from
      respiratory airflow and exhaled air temperature. At rest, breathing frequency f
      (1.4+/-0.3 Hz) and tidal volume Vt (1.9+/-0.4 ml) were independent of T(amb), but
      negatively correlated with each other. Mean ventilation at rest was 156+/-28 ml
      min(-1) at all T(amb). Exhaled air temperature (T(exh)) at rest increased with
      T(amb) (T(exh) = 0.92.T(amb)+12.45). Respiratory water loss at rest averaged
      0.18+/-0.09 ml h(-1) irrespective of T(amb). In flying Starlings f was 4.0+/-0.4
      Hz and independent of T(amb). Vt during flight averaged 3.6+/-0.4 ml and
      increased with T(amb) (Vt = 0.06.T(amb)+2.83) as, correspondingly, did
      ventilation. T(exh) during flight increased with T(amb) (T(exh) =
      0.85.T(amb)+17.29). Respiratory water loss during flight (average REWL(f) =
      0.74+/-0.22 ml h(-1)) was significantly higher than at rest and increased with
      T(amb). Our measurements suggest that respiratory evaporation accounts for most
      water loss in flying Starlings and increases more than cutaneous evaporation with
      rising ambient temperature.

PMID- 17011223
TI  - A follow-up study of MPS I patients treated with laronidase enzyme replacement
      therapy for 6 years.
AB  - Recombinant human alpha-L-iduronidase (Aldurazyme, laronidase) was approved as an
      enzyme replacement therapy for patients with the lysosomal storage disorder,
      mucopolysaccharidosis I (MPS I). In order to assess the long-term safety and
      efficacy of laronidase therapy, 5 of 10 patients in the original laronidase Phase
      1/2 clinical trial were re-evaluated after 6 years of treatment. Lysosomal
      storage was further improved at 6 years (urinary glycosaminoglycans (GAG)
      excretion decreased 76%; mean liver size at 1.84% of body weight). Shoulder
      maximum range of motion was maintained or further increased and reached a mean
      33.2 (R) and 25.0 (L) degrees gained in flexion and 34.0 (R) and 27.3 (L) degrees
      gained in extension. Sleep apnea was decreased in four of five patients and the
      airway size index improved. Cardiac disease evaluations showed no progression to
      heart failure or cor pulmonale but pre-existing significant valve disease did
      progress in some patients. Substantial growth was observed for the pre-pubertal
      patients, with a gain of 33 cm (27%) in height and a gain of 31 kg in weight
      (105%). In general, the evaluated patients reported an improved ability to
      perform normal activities of daily living. Overall these data represent the first
      evidence that laronidase can stabilize or reverse many aspects of MPS I disease
      during long-term therapy and that early treatment prior to the development of
      substantial cardiac and skeletal disease may lead to better outcomes.

PMID- 17011224
TI  - Mitochondrial vitamin B12-binding proteins in patients with inborn errors of
      cobalamin metabolism.
AB  - Inborn errors of vitamin B12 (cobalamin, Cbl) metabolism are autosomal recessive
      disorders and have been classified into nine distinct complementation classes
      (cblA-cblH and mut). Disorders affecting methylcobalamin metabolism cause
      megaloblastic anemia, which may be accompanied by leukopenia and
      thrombocytopenia, and a variety of neurological problems. Disorders affecting
      adenosylcobalamin cause methylmalonic acidemia and metabolic acidosis. Previous
      studies have shown that cobalamin binds to two enzymes in humans: methylmalonyl
      CoA mutase in mitochondria and methionine synthase in the cytosol. In this study,
      cobalamin binding patterns were analyzed in crude mitochondrial fractions
      obtained from both control and patient fibroblasts that had been incubated with
      [57Co]cyanocobalamin. Crude mitochondrial fractions from control fibroblasts
      confirmed that the majority of [57Co]Cbl eluted with methylmalonyl-CoA mutase.
      However, in six of the nine disorders, at least one previously unidentified
      mitochondrial cobalamin binding protein was observed to bind [57Co]Cbl. The
      proportion of [57Co]Cbl that binds, is increased compared to controls when a
      deficiency in either adenosylcobalamin synthesis or utilization prevents binding
      to methylmalonyl-CoA mutase. Furthermore, unique cobalamin binding profiles
      emerged demonstrating how known mutations in these patients affect cobalamin
      binding to as yet unidentified proteins.

PMID- 17011225
TI  - French version of the Copenhagen neck functional disability scale.
AB  - We conducted a study to validate the French version of the Copenhagen Neck
      Functional Disability Scale (CNFDS). METHODS: We used the CNFDS on data generated
      by a previous randomized controlled trial comparing pulsed electromagnetic field
      therapy (PEMFT), spa therapy, and standard therapy in patients with neck pain.
      Patients were recruited locally and examined by a physician who was unaware of
      the treatment group and independent from the trial. Treatment efficacy was
      evaluated based on a visual analog scale (VAS) for pain, the short-form-36
      quality-of-life instrument (SF36), payments by public healthcare insurance, and
      overall assessments by the patients and physicians. Efficacy was evaluated at
      baseline, at treatment completion, and after 3 and 6 months. In addition, the
      patients completed the CNFDS at these time points. RESULTS: CNFDS scores were
      normally distributed. CNFDS scores and their variations correlated well with the
      other efficacy criteria. CNFDS scores were less sensitive to change than the VAS
      pain scores and more sensitive to change than the other efficacy criteria.
      CONCLUSION: The CNFDS holds promise as a tool for evaluating neck pain. Score
      reproducibility needs to be studied. The CNFDS can be added to the other
      instruments that have been translated in recent years to serve as tools for
      clinical research. However, the ease of completion of the CNFDS is consistent
      with use in clinical practice.

PMID- 17011226
TI  - Novel materials for bone and cartilage regeneration.
AB  - Materials that enhance bone and cartilage regeneration promise to be valuable in
      both research and clinical applications. Both natural and synthetic polymers can
      be used to create scaffolds that support cells and incorporate cues which guide
      tissue repair. Recently, electrospinning, peptide self-assembly and
      biomineralisation have been employed to fabricate nanostructured scaffolds that
      better mimic the complex extracellular environment found within tissues, in vivo.
      The incorporation of peptide motifs recognised by cell receptors and the use of
      recombinant DNA technology have enabled the creation of scaffolds with new levels
      of biofunctionality. Advances in materials design will enhance our ability to
      create highly tailored cellular environments for bone and cartilage regeneration.

PMID- 17011227
TI  - MAP65: a bridge linking a MAP kinase to microtubule turnover.
AB  - After the segregation of chromosomes, animal and plant cells build a central
      spindle (midbody) and a phragmoplast, respectively, that are mainly composed of
      aligned microtubules and microfilaments. These microtubule-based structures are
      highly dynamic and play an essential role in cytokinesis. Recent studies using
      model organisms have shed light on the involvement of common molecules in the
      regulatory mechanisms of cytokinesis, including microtubule dynamics, in a
      variety of species. Among these molecules, members of the MAP65 protein family, a
      microtubule-associated protein family, appear to be key regulators of both the
      maintenance and dynamics of central spindles and phragmoplasts.

PMID- 17011228
TI  - Endosperm: an integrator of seed growth and development.
AB  - Plant reproduction relies on interactions between parental and zygotic
      components. Elaborate reciprocal signaling pathways enable coordination of the
      genetic programs between these components. A first and important step in this
      communication is the tight control of cell cycle events in the gametes prior to
      fertilization. This prepares for coordinated fertilization and the initiation of
      seed development. The dialog between the various actors of reproduction extends
      after fertilization, with the endosperm taking a central role. Importantly, the
      endosperm mediates a maternal input that is based on memory of the
      transcriptional states of imprinted genes, which is crucial for harmonious seed
      growth. Our current knowledge suggests that the endosperm is an integrator of the
      different components and genetic programs that are involved in seed development.

PMID- 17011229
TI  - Actin dynamics: old friends with new stories.
AB  - Actin dynamics, or the rapid turnover of actin filaments, play a central role in
      numerous cellular processes. A large and diverse cast of characters, accessory
      proteins known as actin-binding proteins, modulate actin dynamics. They do this
      by binding to the monomer pool, interacting with the side and ends of filaments,
      creating breaks along a filament, and generating new filaments de novo. Recent
      biochemical and single-filament imaging analyses of several conserved classes of
      plant actin-binding proteins reveal unusual and unexpected properties. Examples
      that are highlighted in this review include: an abundant monomer-binding protein
      that catalyzes nucleotide exchange; a barbed-end capping protein that is
      dissociated from filament ends by the signaling lipid, phosphatidic acid; a
      villin-like bundling protein that lacks all Ca(2+)-regulated activities; and a
      formin family member that is non-processive and is sufficient to generate actin
      filament bundles. These and other stories motivate a careful description of the
      properties of plant proteins in vitro as a prelude to greater insight into the
      molecular mechanism(s) underlying the regulation of actin dynamics in vivo.

PMID- 17011230
TI  - Theoretical study of the syn and anti thiophene-2-aldehyde conformers using
      density functional theory and normal coordinate analysis.
AB  - An extensive computational study of thiophene-2-aldehyde conformers syn and anti
      has been carried out using density functional (DFT). From these calculations,
      B3LYP/6-31G(d) has been chosen as it produces results remarkably close in
      comparison with experimental ones, with less demanding computational time. Data
      obtained from DFT computation were used to perform a normal coordinate analysis
      to complement and give insight in the experimental vibrational assignment.
      Calculated dipole moments and relative stabilities of isomers coherently support
      experimental statements given in the literature.

PMID- 17011231
TI  - The hypothesis of Warburg revisited: A metabolic switch in carcinogenesis.

PMID- 17011232
TI  - Nonresponse to adefovir: host or virus dependent?

PMID- 17011233
TI  - Cutaneous disseminated endemic Kaposi's sarcoma in a Polynesian man infected with
      a new divergent human herpesvirus 8 subtype D.

PMID- 17011234
TI  - Maternal mercury exposure and neuro-motor development in breastfed infants from
      Porto Velho (Amazon), Brazil.
AB  - Fish is an important item in the diet of Amazonians, and per se is their best
      single source of essential nutrients. Rapid urbanization and migration are
      bringing changes in dietary habits of Amazonians. Exposure to fish-Hg during
      pregnancy and lactation were studied in 100 women and newborns from Porto Velho.
      Tissue-Hg concentrations and neurodevelopment (Gesell Developmental Schedules)
      were assessed at birth and at 6 months in exclusively breastfed infants. Maternal
      mean frequency of fish consumption was low (<2 meals/week; range 0->7 meals/week)
      compared to Amazonian standards. Women consuming <2 fish meals/week showed less
      median hair-Hg (3.5 microgg-1) than women that consumed 2 fish meals/week (5.7
      microgg). Median total Hg in maternal hair (5.4 microgg-1) was higher than in
      newborns (1.6 microgg-1). Significant correlation was observed between maternal
      hair-Hg and infant hair-Hg at birth (r=0.353; p<0.01) and at six months (r=0.510;
      p<0.01). Placenta-Hg was also significantly correlated to maternal hair-Hg
      (r=0.321; p<0.01), newborn hair-Hg (r=0.219; p<0.05), maternal blood-Hg (r=0.250;
      p<0.01) and to umbilical cord-Hg (r=0.857; p<0.01). Most infants (74%) had normal
      Gesell Schedules but among the 26% showing neuro-motor development delays only
      six (7%) had multiple (motor, language, and adaptative) delays. The infants with
      multiple delays were born from mothers with range of hair-Hg comparable to
      mothers of normally developed infants. Coincidentally, mothers of infants with
      multiple delays also showed the lowest range of income and level of education.
      Fish consumption, income, and level of education varied greatly among these
      breastfeeding urban mothers. It seems that development delays of exclusively
      breastfed infants are a component of the health inequalities that accompanies
      socioeconomic disadvantages.

PMID- 17011235
TI  - Strategies for developing vaccines against H5N1 influenza A viruses.
AB  - Recent outbreaks of highly pathogenic avian influenza A virus (H5N1 subtype)
      infections in poultry and humans (through direct contact with infected birds)
      have raised concerns that a new influenza pandemic might occur in the near
      future. Effective vaccines against H5N1 virus are, therefore, urgently needed.
      Reverse-genetics-based inactivated vaccines have been prepared according to World
      Health Organization (WHO) recommendations and are now undergoing clinical
      evaluation in several countries. Here, we review the current strategies for the
      development of H5N1 influenza vaccines, and future directions for vaccine
      development.

PMID- 17011236
TI  - Deconstructing the molecular portrait of basal-like breast cancer.
AB  - Gene-expression profiling has revealed several molecular subtypes of breast
      cancer, which differ in their pathobiology and clinical outcomes. Basal-like
      tumors are a newly recognized subtype of breast cancer, which express genes that
      are characteristic of basal epithelial cells, such as the basal cytokeratins, and
      are associated with poor relapse-free and overall survival. However, the genetic
      and epigenetic alterations that are responsible for the biologically aggressive
      phenotype of these estrogen receptor-negative and HER2/ErbB2-negative tumors are
      not well understood, thereby hindering efforts to develop targeted therapies.
      Here, we focus on new insights into the molecular pathogenesis of basal-like
      breast cancer and explore how these discoveries might impact the treatment of
      these poor-prognosis tumors.

PMID- 17011237
TI  - How to prevent echocardiographic misinterpretation of Gerbode type defect as
      pulmonary arterial hypertension.
AB  - We present a rare case of left ventricular to right atrial communication, a
      Gerbode type defect discovered in an adult female, originally misinterpreted as
      pulmonary arterial hypertension. The case report will be followed by the review
      of the literature and a discussion about how to prevent echocardiographic
      misinterpretation of this defect as pulmonary arterial hypertension using careful
      echocardiographic examination.

PMID- 17011238
TI  - Echocardiographic manifestations of Adamantiades-Behcet's disease.
AB  - Adamantiades-Behcet disease (ABD) is a multisystemic, chronic inflammatory
      disorder of unknown etiology with diffuse clinical manifestations including those
      involving the cardiovascular system. While the disease is most prevalent in the
      Mediterranean region, the Middle East and the Far East, its prevalence is
      increasing in Western countries due to migration patterns. Cardiovascular
      involvement in ABD may include myocardial disease, venous disease and disease of
      the aorta and great vessels. Use of echocardiography in these patients is crucial
      to assess their pathology and in this article we review the spectrum of
      echocardiographic findings in patients with ABD.

PMID- 17011239
TI  - Carcinoid crisis and reversible right ventricular dysfunction after embolization
      in untreated carcinoid syndrome.
AB  - A 59-year-old white male with carcinoid tumor and hepatic metastases underwent
      hepatic artery embolization. The patient developed carcinoid crisis and a
      subsequent transthoracic echocardiogram showed classic findings of carcinoid
      heart disease along with a dilated hypertrophied right ventricle and severely
      depressed right ventricular ejection fraction. After treatment with octreotide
      the patient's clinical condition improved and a repeat transthoracic
      echocardiogram showed a significant improvement and normalization of right
      ventricular systolic function. Serotonin levels showed a progressive decline that
      correlated well with the patient's improved clinical condition. These findings
      suggest that the acute right ventricular dysfunction was secondary to acute
      carcinoid crisis and resolution resulted in a significant improvement of both
      right ventricular systolic function and clinical condition.

PMID- 17011240
TI  - Death from suicide versus mortality from epilepsy in the epilepsies: a meta
      analysis.
AB  - OBJECTIVE: Epilepsy is associated with an increased risk of mortality, which,
      however, is rarely due to the epilepsy itself; suicide, on the other hand, is a
      chief cause of death among persons with epilepsy. We conducted a meta-analysis to
      compare data reported in representative studies of suicide mortality in epilepsy
      with data on mortality from epilepsy in the general population. METHODS: We
      searched Index Medicus to 2006 through MedLine. We also searched the World Health
      Statistics Annual to ascertain rates of mortality from epilepsy in the age groups
      indicated in the studies on patients with epilepsy for specific years and
      countries. RESULTS: We selected 30 studies comprising 51,216 persons, 188 of whom
      committed suicide and died. Results obtained for each study were processed
      together to calculate, per 100,000 individuals in the general population per
      year, the mean number of suicide deaths expected in persons with epilepsy with
      respect to the current prevalence of epilepsy. We found that the number of
      suicide deaths among persons with epilepsy is the same as the number of deaths
      from epilepsy, suggesting that the former are not included in mortality rates for
      epilepsy. Also, we found that, according to data derived from cohorts we
      selected, 32.5% of all deaths of persons with epilepsy are due to suicide and at
      least 13.5% of all registered suicides are committed by these persons. Study
      findings may not generalize to other samples, settings, and treatments, thus
      perhaps tending to exaggerate the phenomenon actually attainable under broader
      clinical conditions. CONCLUSIONS: Our meta-analysis indicates that suicide deaths
      in persons with epilepsy are a disturbingly frequent phenomenon that should be
      addressed to reduce mortality among patients with epilepsy dramatically. In
      particular, mortality rates for persons with epilepsy do not include mortality
      from suicide, greatly underestimating death rates and the need for suicide
      prevention strategies for these patients.

PMID- 17011242
TI  - Proceedings of the 8th International Conference on the Vascular Endothelium:
      Translating Discoveries into Public Health Practice--part I.

PMID- 17011241
TI  - Factor structure and construct validity of the Chinese Health-Related Quality of
      Life Measure for Youth with Epilepsy.
AB  - PURPOSE: Factor structure and construct validity of the Chinese version of the
      Health-Related Quality of Life Measure for Children with Epilepsy are reported.
      METHODS: The Parent-Proxy Response Scale and Child Self-Report Scale of the
      measure were administered to 266 children and their parents (or primary
      caregivers). Exploratory factor analysis was used to determine the underlying
      factor structure of the instrument. Hypothesis testing was used to explore
      construct validity. RESULTS: The Chinese version of the Health-Related Quality of
      Life Measure for Children with Epilepsy had the same five-factor structure as the
      Canadian version. Greater use of epilepsy-related services was associated with
      poorer quality of life. Quality of life was also poorer in children who had more
      seizures, took more than one anticonvulsant, had impaired cognition, and studied
      in special schools. Children who had close friends and spent more time in
      extracurricular activities with friends scored higher on the Interpersonal/Social
      subscale. CONCLUSIONS: Our data provide evidence of the cross-cultural
      applicability of the translated instrument.

PMID- 17011243
TI  - Hindlimb claudication reflects impaired nitric oxide-dependent revascularization
      after ischemia.
AB  - Although vascular remodeling is important in preventing tissue damage and
      restoring muscle function, there is no evidence of a relationship between
      vascular remodeling and muscle function after peripheral vascular occlusion.
      Nitric oxide (NO) has been implicated in the process of vascular remodeling in
      hindlimb ischemia. Thus, development of alterations in hindlimb gait after
      ischemia may be associated with impaired nitric oxide-dependent, vascular blood
      flow recovery. We evaluated hindlimb gait as an index of ischemia-induced
      revascularization and tested the effects of NO synthase inhibition on both
      hindlimb blood flow and hindlimb gait locomotion. After 14 days of ischemia, the
      ischemic hindlimb showed no significant differences in gait locomotion compared
      to the sham-operated hindlimb. However, hindlimb ischemia drastically reduced
      hindlimb blood flow from 46+/-3 mL/min/100 g to 12+/-2 mL/min/100 g which
      reverted to 33+/-5 mL/min/100 g after 14 days of ischemia. eNOS mRNA expression
      levels at 3, 7, 14, and 28 days after initiation of ischemia, were increased by
      50+/-5%, 100+/-10%, 140+/-8% and 270+/-12% respectively and eNOS protein
      expression levels at 7, 14, and 28 days, were increased by 28+/-3%, 62+/-6% and
      80+/-16% respectively. However, eNOS inhibition caused by l-NAME treatment
      prevented blood flow recovery and correction of abnormal gait locomotion in rats.
      Thus, the duration of the stride-swing phase increased and the stride length
      decreased. The knee joint angle decreased during flexion and extension with eNOS
      inhibition. In conclusion, ischemia-induced revascularization is associated with
      recovery of both hindlimb blood flow and normal gait locomotion. Moreover,
      prevention of NO synthesis, a key messenger in ischemia-induced
      revascularization, is associated with impairment in hindlimb locomotion. Thus,
      gait locomotion represents a functional model that could be used to evaluate the
      degree of ischemia-induced revascularization.

PMID- 17011244
TI  - Impact of arsenite and its methylated metabolites on PARP-1 activity, PARP-1 gene
      expression and poly(ADP-ribosyl)ation in cultured human cells.
AB  - The underlying mechanisms of arsenic carcinogenicity are still not fully
      understood. Mechanisms currently discussed include the induction of oxidative DNA
      damage and the interference with DNA repair pathways. Still unclear is the role
      of biomethylation, which has long been considered to be one major detoxification
      process. Methylated arsenicals have recently been shown to interfere with DNA
      repair in cellular and subcellular systems, but up to now no DNA repair protein
      has been identified being particular sensitive towards methylated arsenicals in
      cultured cells. Here we report that the trivalent methylated metabolites MMA(III)
      and DMA(III) inhibit poly(ADP-ribosyl)ation in cultured human HeLa S3 cells at
      concentrations as low as 1nM, thereby showing for the first time an inactivation
      of an enzymatic reaction related to DNA repair by the trivalent methylated
      arsenicals at very low environmentally relevant concentrations. In contrast the
      pentavalent metabolites MMA(V) and DMA(V) showed no such effects up to high
      micromolar concentrations. All investigated arsenicals did not alter gene
      expression of PARP-1. However, all trivalent arsenicals were able to inhibit the
      activity of isolated PARP-1, indicating that the observed decrease in poly(ADP
      ribosyl)ation in cultures human cells, predominantly mediated by PARP-1, is
      likely due to changes in the activity of PARP-1. Since poly(ADP-ribosyl)ation
      plays a major role in DNA repair, cell cycle control and thus in the maintenance
      of genomic stability, these findings could in part explain DNA repair inhibition
      and the genotoxic and carcinogenic effects of arsenic.

PMID- 17011245
TI  - The influence of a mouthpiece and noseclip on breathing pattern at rest is
      reduced at high altitude.
AB  - The effects of the instrumentation by a mouthpiece (MP) and a noseclip (NC) on
      the ventilatory response to short time hypobaric hypoxia were studied in 10
      healthy volunteers at rest. The subjects were exposed to simulated altitude of
      500 m, 3000 m, 4000 m and again 500 m, each altitude being applied for 30 min in
      a hypobaric chamber. Resting minute ventilation (VE), tidal volume (VT) and
      respiratory frequency (fR) using inductive plethysmography were continuously
      measured in all subjects in a standardized half lying position. The recordings
      were carried out at each altitude during the first 10 min without MP and NC, then
      10 min with them, and the last 10 min again without them. At 500 m during MP+NC
      breathing VE and VT were increased, whereas fR was not significantly changed. At
      3000 m, the VE increase with MP+NC was no more significant and fR was decreased.
      These effects of MP+NC on respiration disappeared at 4000 m and reappeared after
      the descent to 500 m. Furthermore, with and without MP and NC the variability of
      VE at 4000 m was significantly higher than at 500 m before ascent, and in all
      altitudes the variability of VT was significantly reduced by the MP+NC. It is
      concluded that the influence of MP+NC on VE, VT and fR is reduced or even
      abolished at high altitude, whereas the hypoxia induced increase of VE
      variability is not affected by the instrumentation.

PMID- 17011246
TI  - Accurate quantification of dimethylamine (DMA) in human urine by gas
      chromatography-mass spectrometry as pentafluorobenzamide derivative: evaluation
      of the relationship between DMA and its precursor asymmetric dimethylarginine
      (ADMA) in health and disease.
AB  - Dimethylamine [DMA, (CH(3))(2)NH)] is abundantly present in human urine. Main
      sources of urinary DMA have been reported to include trimethylamine N-oxide, a
      common food component, and asymmetric dimethylarginine (ADMA), an endogenous
      inhibitor of nitric oxide (NO) synthesis. ADMA is excreted in the urine in part
      unmetabolized and in part after hydrolysis to DMA by dimethylarginine
      dimethylaminohydrolase (DDAH). Here we describe a GC-MS method for the accurate
      and rapid quantification of DMA in human urine. The method involves use of
      (CD(3))(2)NH as internal standard, simultaneous derivatization with
      pentafluorobenzoyl chloride and extraction in toluene, and selected-ion
      monitoring of m/z 239 for DMA and m/z 245 for (CD(3))(2)NH in the electron
      ionization mode. GC-MS analysis of urine samples from 10 healthy volunteers
      revealed a DMA concentration of 264+/-173 microM equivalent to 10.1+/-1.64
      micromol/mmol creatinine. GC-tandem MS analysis of the same urine samples
      revealed an ADMA concentration of 27.3+/-15.3 microM corresponding to 1.35+/-1.2
      micromol/mmol creatinine. In these volunteers, a positive correlation (R=0.83919,
      P=0.0024) was found between urinary DMA and ADMA, with the DMA/ADMA molar ratio
      being 10.8+/-6.2. Elevated excretion rates of DMA (52.9+/-18.5 micromol/mmol
      creatinine) and ADMA (3.85+/-1.65 micromol/mmol creatinine) were found by the
      method in 49 patients suffering from coronary artery disease, with the DMA/ADMA
      molar ratio also being elevated (16.8+/-12.8). In 12 patients suffering from end
      stage liver disease, excretion rates of DMA (47.8+/-19.7 micromol/mmol
      creatinine) and ADMA (5.6+/-1.5 micromol/mmol creatinine) were found to be
      elevated, with the DMA/ADMA molar ratio (9.17+/-4.2) being insignificantly lower
      (P=0.46). Between urinary DMA and ADMA there was a positive correlation
      (R=0.6655, P<0.0001) in coronary artery disease, but no correlation (R=0.27339)
      was found in end-stage liver disease.

PMID- 17011247
TI  - Acetic acid improves the sensitivity of theophylline analysis by gas
      chromatography-mass spectrometry.
AB  - In the analysis of theophylline by gas chromatography-mass spectrometry (GC-MS),
      we found that the addition of acetic acid to the solvent (ethyl acetate)
      decreased the adsorption of theophylline to the glass wool packed into the inlet
      liner. The addition of acetic acid to ethyl acetate improved the sensitivity for
      theophylline (optimum concentration of 3%). This simple and sensitive method
      without derivatization can be applied to the quantification of theophylline in
      serum samples in clinical and toxicological practice.

PMID- 17011248
TI  - Determination of glibenclamide in human plasma by liquid chromatography and
      atmospheric pressure chemical ionization/MS-MS detection.
AB  - A simple and fast method intended for large-scale bioequivalence studies for the
      determination of glibenclamide in plasma samples is presented. The
      chromatographic separation was achieved on a monolithic octadecyl chemically
      modified silicagel column and a mobile phase containing 42% aqueous 0.1% HCOOH
      solution (v/v) and 58% acetonitrile, at a flow rate of 1 mL/min, in isocratic
      conditions. Preparation of plasma samples was based on protein precipitation with
      acetonitrile. Gliquidone was used as internal standard. The target analytes were
      transferred into an ion trap mass analyzer via an atmospheric pressure chemical
      ionization interface. The precursor ions with mass 494 a.m.u. for glibenclamide
      and 528 a.m.u. for gliquidone were isolated, while in the second MS stage product
      ions 369 a.m.u. and 403 a.m.u., respectively, were monitored. The analytical
      process was characterized by a low limit of quantitation of 1.5 ng/mL. The mean
      recovery for glibenclamide was 98.1+/-2.8% over a concentration interval ranging
      from 1 to 500 ng/mL. Intra-day and inter-day precision calculated over 2-400
      ng/mL concentration interval ranged from 15.4% to 3.4%. Inter-sequence accuracy
      expressed as % bias from theoretical concentration values over the concentration
      interval of 10-400 ng/mL fall within -13.9% and +14.6%. The method was applied
      for evaluation of the bioequivalence between two formulations containing 3.5mg
      glibenclamide per dose.

PMID- 17011249
TI  - Bacterially expressed and refolded envelope protein (domain III) of dengue virus
      type-4 binds heparan sulfate.
AB  - An arboviral infection like dengue fever/dengue hemorrhagic fever (DHF) with high
      morbidity and mortality rate are extensively prevalent in several parts of the
      world. Global efforts have been directed towards development of vaccine for
      prevention of dengue. However, lack of thorough understanding about biology and
      pathogenesis of dengue virus restricts us from development of an effective
      vaccine. Here we report molecular interaction of domain III of envelope protein
      of dengue virus type-4 with heparan sulfate. A codon optimized synthetic gene
      encoding domain III of dengue virus type-4 envelope protein was expressed in
      Escherichia coli and purified under denaturing conditions, refolded and purified
      to homogeneity. Refolded Den4-DIII was characterized using biochemical and
      biophysical methods and shown to be pure and homogeneous. The purified protein
      was recognized in Western analyses by monoclonal antibody specific for the 6x His
      tag as well as the H241 monoclonal antibody. The in vitro refolded recombinant
      protein preparation was biologically functional and found to bind cell free
      heparan sulfate. This is the first report providing molecular evidence on binding
      of dengue-4 envelope protein to heparan sulfate. We developed a homology model of
      dengue-4 envelope protein (domain III) and mapped the possible amino acid
      residues critical for binding to heparan sulfate. Domain III envelope protein of
      dengue virus is a lead vaccine candidate. Our findings further the understanding
      on biology of dengue virus and will help in development of bioassay for the
      proposed vaccine candidate.

PMID- 17011250
TI  - A case report of severe tracheal obstruction requiring extracorporeal membrane
      oxygenation.
AB  - The authors describe the case of a near-fatal airway obstruction requiring
      extracorporeal membrane oxygenation. The patient presented with severe
      respiratory distress owing to a bean impacted in the distal trachea. The foreign
      body could not be removed by bronchoscopy because of instability of the patient.
      The patient was placed on extracorporeal membrane oxygenation for temporary
      pulmonary support, and the foreign body was removed using a rigid bronchoscope.
      The patient had a full recovery and suffered no neurologic sequelae.

PMID- 17011251
TI  - Successful surgical correction of true diphallia, scrotal duplication, and
      associated hypospadias.
AB  - A 1-year-old child with complete duplication of penis presented with continuous
      dribbling of urine. Examination revealed hypospadias of 1 penis and a duplicated
      scrotum with 2 normal testes. Cystourethrogram revealed a single bladder with a
      normal urethra in the dorsally placed phallus and ectopic insertion into the
      bladder of the ventral urethra. Abnormality was corrected by excision of the
      ventrally located penis bearing the ectopic urethra. The preputial skin of this
      ventral penis was used to repair the hypospadias of the dorsal penis. The case is
      being reported in view of its rarity and the successful surgical correction.

PMID- 17011252
TI  - Laparoscopic modified Thal fundoplication for gastroesophageal reflux in a
      patient with severe scoliosis and sliding esophageal hiatal hernia.
AB  - A 14-year-old girl with severe scoliosis and sliding esophageal hiatal hernia
      underwent laparoscopic fundoplication for gastroesophageal reflux. Of various
      fundoplication procedures, anterior partial fundoplication (Thal fundoplication)
      was performed because it is effective, with less postoperative gas bloat
      syndrome. Laparoscopic fundoplication in severely scoliotic children could allow
      improved operative visibility and easier access to the hiatus in comparison with
      the open approach. In our "modified anterior partial fundoplication," the sutures
      between the crura and the esophagus and the sutures on the left of esophageal
      wall with the fundus of the stomach could be exactly performed by laparoscopic
      surgical technique. The wrapping of the esophagus in fundoplication was done over
      the ventral 180 degrees to 270 degrees. Six months postoperatively, the patient
      did not develop gas bloat syndrome, distal esophageal obstruction from
      fundoplication, and delayed gastric emptying. Modified anterior partial
      fundoplication achieves effective control of reflux symptoms.

PMID- 17011253
TI  - Laparoscopic neo-os creation in an adolescent with uterus didelphys and
      obstructed hemivagina.
AB  - Uterus didelphys is a rare congenital anomaly with a well-documented association
      with obstructed hemivagina and ipsilateral renal agenesis. Treatment of this
      anomaly includes drainage of hematocolopos and excision of the vaginal septum,
      which has traditionally used a scalpel or scissors, often with hymenotomy.
      Recently, a less invasive approach using hysteroscopic resection has been
      reported, allowing improved visualization with preservation of the hymenal ring.
      In this article, we present an alternative minimally invasive approach using a
      combination of laparoscopy and vaginoscopy in the case of a 10-year-old girl.
      This approach allows for treatment in cases wherein vaginoscopy provides
      inadequate visualization with the advantage of enabling full evaluation for
      associated complications affecting future fertility including endometriosis,
      pelvic infection, and pelvic adhesions.

PMID- 17011254
TI  - Isolated injury of the superior mesenteric artery caused by a lap belt in a
      child.
AB  - Isolated vascular injuries are rare in cases of blunt abdominal trauma, and
      superior mesenteric artery injury is extremely rare but potentially lethal. The
      incidence of this kind of life-threatening injury has increased in recent years.
      The diagnosis of these isolated injuries is difficult, and its delay is
      associated with a higher morbidity and mortality. The authors report on the case
      of a child with an isolated injury of the superior mesenteric artery caused by a
      lap belt, during a motor-vehicle crash which was successfully managed. Correct
      use of all types of restraints is to be recommended. The diagnosis of this rare
      intraabdominal vascular injury is possible especially when the major signs are
      evident, but an awareness of this rare possibility is essential for the outcome.

PMID- 17011255
TI  - Tracheoesophageal fistula in a child after blunt chest trauma.
AB  - Traumatic tracheoesophageal fistula is a rare complication after blunt chest
      trauma, with all reported cases being more than 12 years of age. We report a 5
      year-old boy with traumatic tracheoesophageal fistula after a blunt injury to the
      chest.

PMID- 17011256
TI  - Periosteal chondroma of the rib possibly associated with hemothorax: a case
      report.
AB  - We report on a case of spontaneous hemothorax occurring in a 13-year-old boy with
      periosteal chondroma of the rib. Periosteal chondromas are rare, particularly in
      the ribs. To the best of our knowledge, this is the first report of periosteal
      chondroma of the rib associated with hemothorax.

PMID- 17011257
TI  - Prenatal diagnosis and multidisciplinary approach to the congenital gingival
      granular cell tumor.
AB  - OBJECTIVE: Congenital gingival granular cell tumor (CGCT) is a rare benign lesion
      appearing at birth on the alveolar median ridge of the maxilla. Etiology is still
      unclear because spontaneous regression of the lesion is rare. METHODS: The
      present report describes 2 cases of neonatal CGCT, highlighting benefits of
      ultrasonography to treatment of the prenatally diagnosed lesion. RESULTS: The
      patients immediately underwent surgical exeresis. Pathology revealed a tumor of
      large polyedric cells with vacuolar central nuclei and eosinophil granular
      cytoplasm. CONCLUSIONS: Prenatal diagnosis is fundamental in the therapeutic
      approach to CGCT: ultrasonography methodologies allow diagnosis of the lesion in
      the uterus at the 36th gestational week, thus also allowing planning of delivery
      and, immediately later, the surgical treatment. That permits planning of delivery
      in a third-level center with considerable benefit for both the mother and the
      newborn.

PMID- 17011258
TI  - Thoracoscopic approach for congenital esophageal stenosis.
AB  - Congenital esophageal stenosis (CES) is an infrequent entity; however, many cases
      have been reported during the last years. Its incidence falls between 1 per
      25,000 and 1 per 50,000 live births and is associated with other congenital
      malformations in 17% to 33% of cases (mainly esophageal atresia). Congenital
      esophageal stenosis is defined as an intrinsic alteration of the esophageal wall
      given by the presence of ectopic tracheobronchial tissue, membranous diaphragm,
      muscular hypertrophy, or diffuse fibrosis of the submucosa, among other causes.
      The therapeutic options include endoscopic dilation and resection plus
      anastomosis (by either laparotomy or thoracotomy, depending on the level of the
      stenosis). We present the case of a 1-month-old baby boy with a CES located in
      the distal esophagus that is associated with anophthalmia and micropenis. We
      treated the lesion by means of a thoracoscopic resection of the affected segment
      and an esophageal end-to-end anastomosis. The patient's long-term outcome was
      uneventful. As far as we know, this is the first report on thoracoscopic
      resolution of a CES.

PMID- 17011259
TI  - Laparoscopic excision of a giant ovarian cyst after ultrasound-guided drainage.
AB  - The laparoscopic approach to giant ovarian cysts in pediatric population may be
      difficult regarding the risk of cyst rupture and limited working space. We herein
      report a 16-year-old adolescent girl that presented with a giant ovarian cyst. To
      reduce the limitations of the laparoscopy, we performed laparoscopy after
      draining the cyst under ultrasonographic guidance. Under local anesthesia, a
      nephrostomy catheter was placed into the cyst by the Seldinger technique. During
      laparoscopy, abdominal cavity was explored by the scope and then the nephrostomy
      catheter was removed. Laparoscopic procedure was completed easily. No pre- and
      postoperative complications were encountered and the patient was discharged on
      the second postoperative day. The pathologic examination of the cyst revealed as
      follicular cyst. Laparoscopic excision of giant ovarian cysts after ultrasound
      guided drainage seems to be safe and applicable treatment modality in children.

PMID- 17011260
TI  - Esophageal atresia. Lessons I have learned in a 40-year experience.
AB  - A brief resume of the highlights in the history of oesophageal atresia is
      presented. This is followed by research into the etiology, ontogeny and
      embryology, and microbiological studies. A revised classification of risk factors
      with consequent survival statistics is presented. Lessons learned in the
      management of the condition over a 40-year period are reported with particular
      emphasis on the management of the preterm infant with associated severe
      respiratory distress, right-side aortic arch, upper pouch fistula, 'long-gap'
      atresia, and the use of gastrostomy and intercostals drains. The incidence and
      treatment of early and late complications is discussed.

PMID- 17011261
TI  - Bilateral Wilms' tumor with anaplasia: lessons from the National Wilms' Tumor
      Study.
AB  - PURPOSE: The purpose of this study was to evaluate whether initial diagnostic
      technique influenced the ability to identify anaplastic histology, to determine
      the time interval to diagnosis of anaplasia, and to delineate the incidence of
      discordant pathology in bilateral Wilms' tumor. We hypothesized that delay in
      diagnosis of anaplasia could affect time to appropriate surgery and intensive
      multimodality therapy. METHODS: One hundred eight-nine children were enrolled in
      the fourth National Wilms' Tumor Study with synchronous bilateral tumors, 27 of
      whom were eventually shown to have anaplastic histology. Initial diagnostic
      technique, time interval to diagnosis of anaplasia, and the incidence of
      discordant pathology were determined. RESULTS: Anaplasia was identified in 0 of 7
      tumors by core needle biopsy, 3 of 9 tumors by open wedge biopsy, and in 7 of 9
      cases by partial or complete nephrectomy. The mean duration of first chemotherapy
      regimen (DD or EE) was 20, 39, and 36 weeks, respectively, before anaplasia was
      identified at second surgery. Discordant pathology between bilateral tumors was
      identified on final tissue diagnosis in 20 patients. Only 4 patients had
      anaplastic tumors in both kidneys. CONCLUSIONS: Core needle biopsy did not
      identify anaplasia in 7 of 7 children. Open biopsy or partial/complete
      nephrectomy identified anaplasia at initial diagnostic procedure in 10 of 18
      children. Twenty of 24 patients at final tissue diagnosis had discordant
      pathology between the 2 kidneys. Earlier interval incisional biopsy or resection
      may identify anaplastic histology and limit the duration of chemotherapy targeted
      to favorable histology for children with bilateral Wilms' tumor and anaplasia.

PMID- 17011262
TI  - Highly resolved free-breathing magnetic resonance cholangiopancreatography in the
      diagnostic workup of pancreaticobiliary diseases in infants and young children-
      initial experiences.
AB  - PURPOSE: A new generation of magnetic resonance imaging scanner offers a 3
      dimensional magnetic resonance cholangiopancreatography (MRCP) with very high
      spatial resolution using a non-breath-hold technique with prospective navigator
      gating. The study aimed to investigate the new technology of the MRCP in infants
      with suspected pancreaticobiliary diseases. METHODS: Seven patients (4 girls, 3
      boys; mean age, 2.8 years; range, 3 months to 5.6 years) were examined. All
      patients underwent magnetic resonance imaging examination using a 1.5-T whole
      body scanner (Magnetom Avanto, Siemens Medical, Erlangen, Germany). For MRCP, a
      heavily T2-weighted (time to echo, 678 ms) 3-dimensional turbo spin echo in
      coronal plane was performed with the voxel size of 1 x 1 x 1.5 mm. To enable non
      breath-holding imaging, a diaphragm navigator sequence was simultaneously carried
      out. The MRCP findings were compared prospectively with the endoscopic retrograde
      cholangiopancreatography and/or with the surgical findings in 6 of 7 cases. In 1
      patient, the follow-up was considered reference standard. RESULTS: The high
      spatial resolution of the images without breathing artifacts allowed an excellent
      demonstration of all relevant pancreaticobiliary ducts and of the pathologic
      findings. All patients (n = 4) with choledocholithiasis were identified through
      MRCP. The finding of a high pancreaticobiliary junction (n = 3) was confirmed by
      endoscopic retrograde cholangiopancreatography in all cases. The length of the
      common channel ranged from 16 to 24 mm. In 1 patient, the long common channel was
      associated with a choledochal cyst. In a 1.7-year-old boy with recurrent
      abdominal pain and mild pancreatitis, the rare case of a gastric duplication with
      connection to the main pancreatic duct was diagnosed. A regular gastric wall with
      normal mucosa and parts of the duodenal wall with a circular layer of muscle
      (pylorus-like) were found in histology after surgical resection of the mass.
      CONCLUSION: The newly developed technique may be a reliable tool in the workup of
      pancreaticobiliary diseases in infants.

PMID- 17011263
TI  - Dynamic study of pancreaticobiliary reflux using secretin-stimulated magnetic
      resonance cholangiopancreatography in patients with choledochal cysts.
AB  - BACKGROUND/PURPOSE: Refluxes through pancreaticobiliary maljunctions play an
      important role in the pathophysiology of choledochal cysts. Dynamic studies of
      the pancreaticobiliary tract were performed using secretin-stimulated magnetic
      resonance cholangiopancreatography. METHODS: Six patients with choledochal
      dilation were recruited for this study. Four patients exhibited cystic and 2
      exhibited fusiform dilatation of the common bile duct (CBD). Magnetic resonance
      cholangiopancreatography images were obtained every minute during the 15-minute
      period after secretin stimulation. The sequential morphological changes in the
      biliary trees, pancreas, and duodenum were assessed, and the total pixel values
      of these organs were measured for each image, then plotted as a ratio against the
      baseline image. RESULTS: In 2 cases involving cystic dilatation, the intensity of
      bile duct images continued to rise after secretin stimulation. In a case
      involving fusiform dilatation, a transitory elevation in CBD intensity was
      observed. In 3 cases involving fusiform or cystic dilatation, the intensity of
      CBD did not change notably. In all cases, the duodenum was filled well after
      secretin stimulation. CONCLUSIONS: The sustained elevation in bile duct intensity
      after secretin stimulation indicates reflux and bile stasis. Transitory elevation
      may indicate reflux without stasis. This method allows assessment of the dynamics
      of pancreatic and bile fluid under more physiologic condition.

PMID- 17011264
TI  - The significance of serum hepatocyte growth factor levels in planning follow-up
      of postoperative jaundice-free patients with biliary atresia.
AB  - PURPOSE: The aim of this study was to clarify the significance of serum
      hepatocyte growth factor (HGF), interleukin (IL)-6, and IL-1 receptor antagonist
      (ra) levels in the evaluation of disease status in jaundice-free survivors with
      biliary atresia after Kasai operation. PATIENTS AND METHODS: Serum concentrations
      of HGF, IL-6, and IL-ra were measured in 31 long-term jaundice-free patients with
      biliary atresia after Kasai operation and 29 controls. Patients were divided into
      4 groups: group A (n = 8), normal liver function; group B (n = 9), mild liver
      dysfunction without portal hypertension; group C (n = 9), moderate liver
      dysfunction with controllable portal hypertension; and group D (n = 5), receiving
      liver transplantation. RESULTS: Serum IL-6 levels were significantly higher in
      patients than in controls. There was no difference in serum IL-6 levels among
      groups B, C, and D. Serum IL-1ra levels were elevated according to liver
      dysfunction. Serum HGF levels in group D were significantly higher than in
      controls and the other groups. Serum hyaluronic acid levels were positively
      correlated with serum levels of IL-1ra and HGF. CONCLUSIONS: Elevation of serum
      IL-1ra and HGF levels correlated with the progression of liver fibrosis and
      dysfunction. In particular, serum HGF levels could be used as a predictor for
      requiring liver transplantation.

PMID- 17011265
TI  - Oxidative injury and hepatocyte apoptosis in total parenteral nutrition
      associated liver dysfunction.
AB  - PURPOSE: The aim of this study was to investigate the impact of oxidative injury
      and apoptosis on total parenteral nutrition (TPN)-associated hepatic dysfunction.
      METHODS: Fifty-nine New Zealand rabbits (6-8 days old) were divided into 4
      groups: 12 in the control group (maternal fed), 15 in the PN-3 group (TPN for 3
      days), 14 in the PN-7 group (TPN for 7 days), and 18 in the PN-10 group (TPN for
      10 days). At the end of the experiment, blood biochemistry analysis and
      histologic examination of the liver were performed; the malondialdehyde content
      of liver tissues was determined and hepatocyte apoptosis was evaluated by
      terminal deoxynucleotidyl transferase-mediated nick-end labeling assay. RESULTS:
      We found that the serum level of direct bilirubin became higher as PN duration
      was extended. The light microscopy features in the PN-3 and PN-7 groups included
      inflammatory cells infiltrated in portal areas and some degeneration changes,
      whereas in the PN-10 group, cholestasis (proliferation of bile ducts and bile
      pigments in hepatocytes) or diffuse steatosis was shown. Electron microscopic
      manifestation in PN groups included reduced numbers of microvilli and some
      preapoptosis changes. Both the malondialdehyde content and apoptosis index were
      the highest in the PN-10 group; there were more apoptotic hepatocytes in the
      groups with longer PN duration. CONCLUSIONS: The longer the TPN duration, the
      more severe the liver injury. Both oxidative injury and apoptosis may play
      important roles in the mechanism of TPN-associated hepatic dysfunction.

PMID- 17011266
TI  - Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell
      infiltration in cholestatic rats receiving biliary intervention.
AB  - AIM: Biliary intervention may augment chemokine expression and inflammatory cell
      infiltration and aggravates liver injury in cholestatic rats. We tested the
      efficacy of glucocorticoid pretreatment to prevent the complications. METHODS: A
      model of biliary intervention was established in rats without (sham) or with bile
      duct ligation (BDL). Before biliary intervention, rats were randomly assigned to
      receiving intravenous injection of dexamethasone (DX group) or normal saline (NS
      group). Plasma levels of monocyte chemoattractant protein-1 (MCP-1) and
      macrophage inflammatory protein-2 (MIP-2) were measured with enzyme-linked
      immunosorbent assay, and liver messenger RNA of these chemokines was quantified
      with real-time quantitative reverse transcriptase-polymerase chain reaction.
      Monocytes, Kupffer cells, and neutrophils in the rat liver were characterized
      with antibodies to ectodermal dysplasia 1 (ED1), ED2, and myeloperoxidase,
      respectively. RESULTS: By 3 hours after biliary intervention, plasma MCP-1 and
      MIP-2 proteins in BDL-NS rats were significantly higher than in BDL-DX. At 3
      hours, liver MCP-1 and MIP-2 messenger RNA levels were significantly upregulated
      in BDL-NS than in BDL-DX. The amount of ED1-, ED2- and myeloperoxidase-staining
      cells were significantly greater in BDL-NS than in BDL-DX. Most of the changes
      returned to baseline levels by 24 hours. CONCLUSION: Glucocorticoid pretreatment
      suppresses chemokine expression and inflammatory cell infiltration, which may
      consequently alleviate liver injury in cholestatic rats receiving biliary
      intervention.

PMID- 17011267
TI  - Comparison of outcomes after laparoscopic and open pyloromyotomy at a high-volume
      pediatric teaching hospital.
AB  - BACKGROUND/PURPOSE: Laparoscopic pyloromyotomy (LP) is used widely for treatment
      of hypertrophic pyloric stenosis. We examined the results of pyloromyotomy at a
      high-volume pediatric teaching hospital to compare outcomes of laparoscopic and
      open pyloromyotomy (OP). METHODS: We reviewed the records of all patients who
      underwent pyloromyotomy at our institution over a 5-year period. Data were
      collected regarding operative time, time to full feeds, length of hospital stay,
      complications, and frequency of postoperative emesis. RESULTS: There were 335
      pyloromyotomies: 212 laparoscopic and 123 open. Five patients in the laparoscopic
      group required conversion to an open procedure. There were no significant
      differences in operative time (LP, 30.5 minutes; OP, 32.0 minutes), time to full
      feeds (LP, 22.4 hours; OP, 23.5 hours), frequency of postoperative emesis (LP,
      1.8; OP, 2.2), or length of hospital stay (LP, 49.3 hours; OP, 50.5 hours). There
      were 5 mucosal perforations in the laparoscopic group and 2 in the open group
      (LP, 2.3%; OP, 1.6%). There were 3 incomplete pyloromyotomies in the laparoscopic
      group and none in the open group. Four perforations and all incomplete myotomies
      occurred in the first 2 years after the laparoscopic technique was introduced at
      our institution. The overall complication rate was similar (LP, 3.7%; OP, 3.2%).
      CONCLUSIONS: Laparoscopic pyloromyotomy is a safe and effective alternative to
      OP. There appears to be an institutional learning curve when the laparoscopic
      technique is introduced as reflected by slightly higher rates of mucosal injury
      and incomplete pyloromyotomy.

PMID- 17011268
TI  - Optimal enteral feeding in children with gastric dysfunction: surgical
      jejunostomy vs image-guided gastrojejunal tube placement.
AB  - PURPOSE: Long-term feeding access in children who fail initial gastrostomy is a
      management quandary. Although image-guided gastrojejunal feeding tube placement
      (IGJ) is becoming the access of choice in many centers, few studies have compared
      long-term results with surgical jejunostomy (SJ). The authors compare outcomes
      with these 2 techniques. METHOD: A retrospective review of 20 children requiring
      jejunal feeding access after failing initial gastrostomy was done. Procedures
      were performed at a tertiary referral center by interventional radiologists (IGJ)
      or board-certified pediatric surgeons (SJ). RESULTS: Initially, patients
      underwent IGJ (n = 14) or SJ (n = 6). Image-guided gastrojejunal feeding tube
      placement patients required gastrostomy at an average age of 23.8 months, with
      conversion to IGJ an average of 17.2 months later. SJ patients required
      gastrostomy at average age of 16.2 months, with conversion to SJ 30.7 months
      later. Of 14 patients undergoing IGJ, 7 (50%) eventually required SJ because of
      recurring tube management issues. Thus, 13 patients ultimately had SJ, with 11
      (85%) Roux-en-Y jejunostomies. Mean operating time for SJ was 158 minutes, with
      an average of 5.1 days to initiation of feeds, 11 days to full feeds, and 19.9
      days to discharge (range, 3-66 days). Image-guided gastrojejunal feeding tube
      placement patients averaged 4.6 tube adjustments per year requiring fluoroscopic
      guidance. Surgical jejunostomy averaged 1.5 tube adjustments per year requiring
      outpatient hospital visits. Image-guided gastrojejunal feeding tube placement
      patients averaged 3.9 hospital d/y secondary to feeding tube management issues,
      whereas SJ patients averaged 1.4 hospital days per year. CONCLUSION: In this
      group of children with long-term jejunal feeding access, half of those with IGJ
      eventually required SJ. Surgical jejunostomy required fewer adjustments and
      hospitalizations per year. Although initially more invasive than IGJ, SJ may
      provide more stable feeding access with fewer complications. This represents the
      first published report comparing long-term outcomes between IGJ and SJ.

PMID- 17011269
TI  - Peroperative Gastrograffin bowel lavage in gastroschisis.
AB  - AIMS: The aim of the study was to evaluate potential benefits in the use of
      peroperative bowel lavage with Gastrograffin in neonates with gastroschisis.
      METHODS: A retrospective analysis of newborns with gastroschisis was performed
      over a 10-year period in 2 centers in the United Kingdom. Two groups were studied
      wherein one had peroperative bowel lavage with Gastrograffin and the other did
      not. RESULTS: Data were collected on 116 patients of whom 93 were suitable for
      analysis. There were no statistically significant differences in primary closure
      rate, duration of ventilation, parenteral nutrition, or hospital stay. Intestinal
      obstruction occurred more frequently in the nonlavage group. CONCLUSION:
      Gastrograffin lavage peroperatively in gastroschisis offers no potential
      advantage in reducing ventilatory requirements, parenteral nutrition, and
      hospital stay. It also does not achieve greater primary closure rates, but may
      reduce the incidence of intestinal obstruction.

PMID- 17011270
TI  - Effects of trapidil on renal ischemia-reperfusion injury.
AB  - There is increasing evidence to suggest that reactive oxygen and nitrogen species
      play a role in the pathogenesis of renal ischemia-reperfusion (I/R) injury. This
      study was designed to determine the possible protective effects of trapidil
      treatment against oxidative and nitrosative tissue injury of kidney induced by
      I/R. A renal I/R injury was induced by a left renal pedicle occlusion by ischemia
      for 45 minutes, followed by 1 hour of reperfusion with contralateral nephrectomy
      in I/R and I/R + trapidil groups. Trapidil (8 mg/kg intravenously) was
      administrated immediately before reperfusion phase. At the end of the reperfusion
      period, rats were killed. Then, renal tissue samples were taken for biochemical
      analysis and histopathological evaluation, and blood samples were obtained to
      determinate serum urea, aspartate aminotransferase (AST), and tumor necrosis
      factor-alpha (TNF-alpha) levels. Ischemia-reperfusion injury caused significant
      increases in myeloperoxidase activity and malondialdehyde and 3-nitrotyrosine
      levels in renal tissue and elevated serum urea, AST, and TNF-alpha levels. In
      addition, severe deterioration of renal morphology was seen in the I/R group.
      Trapidil treatment significantly reduced in biochemical parameters, as well as
      serum urea, AST, and TNF-alpha levels. Furthermore, renal tissue injury was
      markedly attenuated with trapidil treatment. These data suggest that reactive
      oxygen species and reactive nitrogen species play a causal role in I/R-induced
      renal tissue, and trapidil has a renoprotective effect against oxidative and
      nitrosative kidney damage.

PMID- 17011271
TI  - The catheter is stuck: complications experienced during removal of a totally
      implantable venous access device. A single-center study in 200 children.
AB  - BACKGROUND: Totally implantable venous access devices (TIVAD) facilitate repeat
      intravenous therapy for children. Many children recover and the device may be
      removed. Although removal should be a simple procedure via a single incision, in
      our experience, this has not been the case. METHODS: Two hundred consecutive
      cases of removal of TIVAD from September 2000 to January 2004 at Sophia
      Children's Hospital, Rotterdam, were reviewed. RESULTS: Average patient age was
      5.9 years. The commonest indication for placement was administration of
      chemotherapy (88%); commonest indication for removal was remission of disease
      (70%). The median duration in situ of the catheter was 29 months (range, 0.4-91
      months). Complications with removal of the polyurethane catheter of the TIVAD
      were experienced in 16% of cases. To enable removal, a second incision was
      required in 28 patients, venotomy in 5; the catheter could not be removed in 3.
      For all complicated removals the catheter had been in situ for longer than 20
      months. CONCLUSIONS: Long-term implantation of TIVAD with polyurethane catheter
      appears unsuitable owing to a high incidence of complication at time of removal.

PMID- 17011272
TI  - Family study of the inheritance of pectus excavatum.
AB  - BACKGROUND: The most common congenital deformity of the chest wall is pectus
      excavatum, a malformation that is present in between 1 in 400 and 1 in 1000 live
      births and causes the body of the sternum to be displaced, producing a
      depression. There are many different shapes of the pectus, and multiple factors
      probably contribute to the final form. The etiology of pectus excavatum is
      uncertain, but a familial tendency has been found in clinical experience, where
      it may be seen in more than one sibling. Pectus excavatum is commonly associated
      with connective tissue disorders such as Marfan and Ehlers Danlos syndromes.
      Extensive literature review failed to identify articles documenting families with
      multiple affected members. PURPOSE: The purpose of this study was to collect
      evidence that pectus excavatum is familial and may be an inherited disorder.
      METHODS: Using the Children's Surgical Specialty Group database at Children's
      Hospital of The King's Daughters, families with more than one affected individual
      were selected. With Institutional Review Board-approved informed consent, 34
      families agreed to participate. Family histories were obtained, and a 4
      generation pedigree was constructed for each family. Forty questions were asked
      about each individual's medical history, and comprehensive systems review
      included features of connective tissue-related problems. Inheritance patterns for
      each family were determined by pedigree analysis. RESULTS: A total of 14 families
      suggested autosomal dominant inheritance, 4 families suggested autosomal
      recessive inheritance, and 6 families suggested X-linked recessive inheritance.
      Ten families had complex inheritance patterns. Pectus excavatum occurred more
      frequently in males than in females (1.8:1). Long arms, legs, and fingers; high
      arched palate; mitral valve prolapse; heart arrhythmia; scoliosis; double
      jointedness; flexibility; flat feet; childhood myopia; poor healing; and easy
      bruising were commonly associated with pectus excavatum. CONCLUSIONS: Pedigree
      analysis of 34 families provides evidence that pectus excavatum is an inherited
      disorder, possibly of connective tissue. Although some families demonstrate
      apparent Mendelian inheritance, most appear to be multifactorial.

PMID- 17011273
TI  - An approach to minimize postoperative enterocolitis in Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Enterocolitis (EC) is a common and severe complication after
      pull-through for Hirschsprung's disease; its pathogenesis remains unclear, but
      the role of coexistent intestinal neuronal dysplasia (IND) in the proximal colon
      may be relevant. This study evaluated the relationship between postoperative EC
      and IND and assessed whether a surgical protocol including resection of
      coexistent IND could prevent postoperative EC. METHODS: Between June 1993 and
      June 2002, 36 patients with aganglionosis were submitted to definitive surgical
      treatment. There were 2 sequential sets of patients: group I (n = 17), in whom
      the resection was confined to the aganglionic colon, and group II (n = 19), who
      were additionally submitted to resection of the coexistent IND segment; excision
      was restricted to the hepatic flexure in long segmental IND. The prevalence of
      postoperative EC and anorectal function were evaluated and compared between the 2
      groups. RESULTS: There was no mortality. Fifteen patients had isolated
      aganglionosis, and 21 presented with aganglionosis plus proximal IND. All 6
      children who developed postoperative EC had coexistent IND. In group I, 9
      patients had coexistent IND and 5 developed postoperative EC (5/17, 29%). In
      group II, 12 patients had coexistent IND but only 1 patient, with long segmental
      IND, developed postoperative EC (1/19, 5%). Among the patients with proximal IND,
      the prevalence of postoperative EC was 29%; but it was significantly lower in
      group II than in group I (1/12 or 8% vs 5/9 or 56%; P = .02). Anorectal function
      was excellent or good in more than 80% of the patients in both groups.
      CONCLUSIONS: Postoperative EC was associated with retained proximal IND,
      suggesting that coexisting IND may be, at least, a predictive marker for this
      complication. Histochemical characterization of the proximal colon with no
      radical resection of the IND segment seems to be an effective and safe approach
      to minimize the prevalence of postoperative EC.

PMID- 17011274
TI  - New variations of the EDNRB gene and its association with sporadic Hirschsprung's
      disease in Korea.
AB  - BACKGROUND/PURPOSE: The endothelin receptor B (EDNRB) signaling pathway, which is
      the second major susceptible gene for Hirschsprung's disease (HSCR), is crucial
      for the development of the enteric nervous system. The allele frequency of
      polymorphisms was mostly tested in the American and European population, but the
      data of an ethnically diverse, non-Caucasian population are unclear. To further
      investigate the variants and haplotypes of the EDNRB gene, this study examined
      sequence variations in Korean patients with sporadic HSCR. METHODS: All 8 exons
      and intron/exon boundaries of the EDNRB gene in 18 Korean patients with sporadic
      HSCR and 84 healthy individuals were screened using PCR amplification and direct
      sequencing. RESULTS: A total of 8 different nucleotide substitutions were
      identified. Of these, 4 were new variants (promoter-116C>T; 5'UTR-121G>T;
      IVS4+62C>A; IVS5+121G>C) and the others were previously described variants. The
      distribution of variations was even different from that reported for Chinese and
      Japanese subjects as well as other ethnic groups. This study also analyzed the
      haplotypes for an association between the variants identified with HSCR.
      CONCLUSIONS: This study identified additional sequence variants of the EDNRB
      gene, but the estimated EDNRB haplotypes did not show any disease risk.

PMID- 17011275
TI  - Thoracoscopic repair for congenital diaphragmatic hernia: lessons from 45 cases.
AB  - PURPOSE: To describe the surgical technique, initial results, and overview
      indications of thoracoscopic repair of congenital diaphragmatic hernia (CDH).
      MATERIALS AND METHODS: A retrospective review was undertaken of patients with CDH
      who underwent thoracoscopic repair by the same surgeon from January 2001 to
      January 2005. Patients underwent surgery under general anesthesia. Reduction of
      the hernia contents was carried out using 1 optical trocar and 2 operating
      trocars. Pleural insufflation with carbon dioxide was maintained at a pressure of
      2 to 4 mm Hg. The hernia defect was repaired using nonabsorbable interrupted
      sutures with extracorporeal knots. RESULTS: There were 45 patients, including 29
      boys and 16 girls. Among 19 newborn patients, there were 13 patients younger than
      7 days. The other 26 patients were infants and elders. The hernia was located in
      the left side in 37 patients and in the right side in 8 patients. The mean
      operative time was 54 minutes. Conversion was required in 4 patients. There were
      no complications. However, there were 2 postoperative deaths. CONCLUSIONS:
      Thoracoscopic repair is feasible and safe for children with CDH, including
      selective newborn. The technique causes minimal trauma, results in good
      respiratory function, and promotes early recovery.

PMID- 17011276
TI  - Lung function in infants after repair of congenital diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is initially
      characterized by severe restrictive lung defect and low lung compliance, but
      survivors have relatively few abnormalities later in life. We studied the changes
      in lung growth and function in infants after the repair of CDH. METHODS:
      Retrospective analysis of pulmonary function tests was performed during the first
      24 months of life in 56 infants (33 male and 23 female) after repair of CDH. Lung
      function (functional residual capacity [FRC], respiratory system compliance
      [C(rs)] and resistance [R(rs)], and maximum expiratory flow rate at FRC
      [V'(maxFRC)]) were compared among 4 different ages (0-3, 4-6, 7-12, and 13-24
      months). RESULTS: All indices of lung function (mean +/- SD of z scores) were
      abnormal during the first 6 months of life but were almost normalized by 24
      months (P < .0001): FRC, from -0.84 +/- 0.5 to 3.26 +/- 2.07; C(rs), from -0.87
      +/- 0.4 to 1.84 +/- 1.75; R(rs), from 2.85 +/- 2.71 to -0.23 +/- 2.03, and
      V'(maxFRC), from -1.63 +/- 0.4 to -0.09 +/- 0.94. There was significant
      correlation (P < .001) between lung function and increase in age, height, and
      especially weight. CONCLUSIONS: Lung growth and function gradually normalize
      between 6 and 24 months of life after repair of CDH.

PMID- 17011277
TI  - Approach to diagnosis and treatment of pediatric primary tumors of the diaphragm.
AB  - BACKGROUND/PURPOSE: Tumors of the diaphragm in the pediatric population are
      extremely rare. We present 5 cases diagnosed at the Hospital for Sick Children,
      Toronto, and together with a review of the world literature, provide an approach
      to the diagnosis and management of these tumors. METHODS: A clinical
      retrospective review of patients diagnosed as having primary diaphragmatic tumor
      (PDT) at the Hospital for Sick Children as well as a review of the world
      literature. RESULTS: Forty-one cases of PDT in the pediatric population have been
      described from 1868 to 2005 inclusive. There is an equal incidence in boys and
      girls, they are found with the same frequency on the left as on the right, and
      78% are malignant. Rhabdomyosarcoma is the most commonly occurring malignant
      tumor. The mean age at diagnosis is 10 years. "Chest-associated" symptoms are
      more common than "abdomen-associated" symptoms. Imaging often fails to identify
      the site of origin as the diaphragm. Surgery is the cornerstone of therapy for
      PDT. CONCLUSION: A multidisciplinary team approach is needed for successful
      treatment and management of PDT.

PMID- 17011278
TI  - Diaphragmatic injuries in children after blunt abdominal trauma.
AB  - BACKGROUND: Traumatic rupture of the diaphragm resulting from blunt abdominal
      trauma remains a challenging clinical entity. Description of such type of
      injuries in children is scarce in the literature. PURPOSE: The aim of this study
      was to present this special form of injury in the pediatric age group and compare
      the different aspects of diaphragmatic injury with that occurring in adults.
      PATIENTS AND METHODS: Ten cases of diaphragmatic rupture after blunt trauma in
      children were reported. The presentations, findings, and management were
      described. RESULTS: This study included 7 boys and 3 girls aged 3 to 16 years.
      Trauma in 8 cases resulted from motor vehicle or auto-pedestrian accidents and 2
      from falling from a height. Chest radiograph shows suggestive signs of
      diaphragmatic injuries in 7 occasions including intrathoracic visceral herniation
      in 4 cases and hemothorax in 3 cases. Associated injuries were found in 5 cases
      in the form of rib fractures in 3 cases and lung contusion in 2 cases. Lung tear,
      gut perforation, and liver tear were each reported once. Isolated diaphragmatic
      injury is reported in 5 cases. Three cases were repaired via thoracotomy or
      laparo-thoracotomy and 7 cases via midline laparotomy. On exploration, we found
      diaphragmatic avulsion of the costal origin in 5 cases, 3 left and 2 right
      contrary to tears, of which 4 were left sided and 1 right sided. Primary repair
      was conducted in 7 cases and an intercostal muscle flap was used in 3 cases. No
      mortalities were reported. CONCLUSIONS: This series of diaphragmatic rupture in
      children reveals the following: (1) Avulsion of the costal origin of the
      diaphragm is a peculiar type of injury described in children (5 of 10). (2) The
      intercostal muscle flap is a useful tool to bridge diaphragmatic defects. (3)
      Isolated diaphragmatic injuries do occur in children more frequently than in
      adults. (4) As in adults, diaphragmatic rupture prevails in the left side, and
      purposeful surgical diagnosis and early management determine the effectiveness of
      treatment.

PMID- 17011279
TI  - Thoracoscopy in pediatric pleural empyema: a prospective study of prognostic
      factors.
AB  - PURPOSE: The indications for thoracoscopy remain imprecise in cases of pleural
      empyema. This study aimed to identify preoperative prognostic factors to help in
      the surgical decision. METHODS: From 1996 to 2004, 50 children with parapneumonic
      pleural empyema underwent thoracoscopy either as the initial procedure (n = 26)
      or after failure of medical treatment (n = 24). Using multivariate analysis, we
      tested the prognostic value of clinical and bacteriological data, the
      ultrasonographic staging of empyema, and the delay before surgery. Outcome
      measures were technical difficulties, postoperative complications, time to
      apyrexia, duration of drainage, and length of hospitalization. RESULTS: The
      clinical and bacterial data did not significantly predict the postoperative
      course. Echogenicity and the presence of pleural loculations at ultrasonography
      were not independent significant prognostic factors. A delay between diagnosis
      and surgery of more than 4 days was significantly correlated (P < .05) with more
      frequent surgical difficulties, longer operative time, more postoperative fever,
      longer drainage time, longer hospitalization, and more postoperative
      complications, such as bronchopleural fistula, empyema relapse, and persistent
      atelectasia. CONCLUSION: The main prognostic factor for thoracoscopic treatment
      of pleural empyema is the interval between diagnosis and surgery. A 4-day limit,
      corresponding to the natural process of empyema organization, is significant. The
      assessment of loculations by ultrasonography alone is not sufficient to predict
      the postoperative course.

PMID- 17011280
TI  - Extrapleural pneumonectomy in children.
AB  - BACKGROUND/PURPOSE: Extrapleural pneumonectomy (EPP) is an en bloc resection of
      the pleura, lung, diaphragm, and pericardium. EPP in the pediatric population has
      not been reported in the literature. We report our experience of using EPP in
      children to treat a variety of malignancies that involve the pleural surface.
      METHODS: We performed a retrospective review of all children treated through EPP
      at our institution. Data were obtained from patient charts and a pediatric
      database. All patients underwent en bloc resection of the pleura, lung,
      diaphragm, and pericardium and reconstruction. RESULTS: Four patients underwent
      EPP from 2000 to 2004 for inflammatory myofibroblastic tumor, spindle cell
      sarcoma, metastatic neuroblastoma, and malignant mesothelioma. The patients' ages
      were from 6 to 11 years. The patient with metastatic neuroblastoma had recurrent
      disease in the left chest 1 year after EPP and died of sepsis; the patient with
      mesothelioma died of disease extension into the abdomen 1.5 years later. The
      other 2 patients are free of disease. CONCLUSIONS: EPP can be performed with
      curative intent in selected pediatric patients with pleural-based malignancies.
      EPP should be included in the armamentarium of the pediatric thoracic surgeon and
      evaluated in larger studies.

PMID- 17011281
TI  - L-NAME-induced neutrophil accumulation in rat lung is not entirely because of
      interactions with L- and P-selectins or CD18.
AB  - BACKGROUND/PURPOSE: Nitric oxide (NO) is a known selective dilator of the
      pulmonary vascular tree. There is evidence that it also plays a role in
      diminishing neutrophil adherence to vascular endothelial cells. Close examination
      of these effects of NO on the pulmonary microcirculation is essential to our
      understanding of its mechanisms of action as well as its potential as a
      therapeutic agent to reduce neutrophil sequestration, and its subsequent damage,
      in a variety of conditions that cause lung injury and inflammation. This study
      explores the mechanism by which endogenous NO influences neutrophil-endothelial
      cell interactions by examining the effects of the adhesion molecule blockers,
      fucoidin, and anti-CD18 antibody. METHODS: Lung samples from 10 sets of rats (n =
      4 for each study group) were studied. Each rat received an intravenous bolus of
      normal saline, fucoidin, or anti-CD18 antibody, followed by a 1-hour infusion of
      normal saline or N omega-nitro-L-arginine methyl ester (L-NAME) at 2 mg kg(-1)
      min(-1). The accumulation of neutrophils within the lungs was assessed
      quantitatively by myeloperoxidase assay. RESULTS: Fucoidin application decreased
      some neutrophil activity, but this may have been independent of the effects on L
      NAME activity. The anti-CD18 pretreatment did not have a significant effect on
      any of the groups in the presence or absence of L-NAME. CONCLUSIONS: These data
      indicate that L-NAME does not conclusively produce its associated increase in
      neutrophil activity in the baseline state of the lungs via an interaction with L
      selectin, P-selectin, or CD18. Rather, the inhibition of NO may lead to the
      expression of a different adhesion molecule or factor that is normally not
      expressed in the presence of NO. Endogenous NO may also possibly influence
      neutrophil-endothelial interaction by affecting hemodynamics rather than actions
      of adhesion molecules.

PMID- 17011282
TI  - Left colonic antegrade continence enema: experience gained from 19 cases.
AB  - PURPOSE: As problems have developed with the right colonic antegrade continence
      enema procedure (Malone's procedure/Monti's retubularized ileocolostomy), left
      colonic antegrade continence enema (LACE) procedure, in which retubularized ileum
      or sigmoid colon is anastomosed into the sigmoid colon, has gained popularity.
      The aim of the study was to describe our experience with the LACE procedure.
      METHODS: We retrospectively reviewed 19 LACE procedures that were performed at
      the Yonsei University College of Medicine Hospital (Seoul, Korea) from March 2001
      to March 2005. RESULTS: Male-to-female ratio was 11:8, with median age of 10
      years (range, 3-34 years). Most common diagnosis was meningomyelocele (78.9%,
      15/19). The median total follow-up period was 23 months (range, 3-37 months);
      median antegrade continence enema volume used was 600 mL (range, 250-1500 mL);
      and median transit time was 30 minutes (range, 15-60 minutes). Patients performed
      antegrade continence enema with an average of once every 2 days (range, 0.3-3
      days). Social continence was achieved in 14 patients (73.7%). Regurgitation of
      fecal material through stoma was not reported at all in 17 patients (89.5%).
      CONCLUSIONS: We recommend LACE as the procedure of choice for children with
      congenital malformations or any other condition predisposing to fecal
      incontinence or constipation intractable to conventional treatment.

PMID- 17011283
TI  - Pilomatrixoma--accuracy of clinical diagnosis.
AB  - BACKGROUND/PURPOSE: Pilomatrixoma is a common tumor of skin appendages in
      children. The aim of the study was to assess the accuracy of clinical diagnosis
      and factors contributing to misdiagnosis. METHODS: A retrospective case note
      review of patients who had pilomatrixoma excised during a 5-year period in a
      tertiary referral children's hospital in the UK. RESULTS: From 75 patients, 78
      pilomatrixomata were excised. The diagnosis was achieved preoperatively in 46% of
      patients. Other diagnoses included sebaceous and dermoid cysts, foreign body
      reaction, calcification in lymph gland, and fat necrosis. CONCLUSION: Factors
      contributing to misdiagnosis include cystic lesions with varying consistency,
      punctum-like appearance, atypical location, and absence of clinically
      recognizable calcification. Despite close excision, the recurrence rate is low.

PMID- 17011284
TI  - Teratoid Wilms' tumor: a case report with literature review.
AB  - Teratoid Wilms' tumor is an unusual histologic variant of nephroblastoma in which
      the heterologous tissue predominates. The treatment for this tumor has not been
      established because of its rarity and varying tumor components. The authors
      report a case of localized teratoid Wilms' tumor in a 4-month-old male infant
      successfully treated with nephrectomy only. The tumor originated from the right
      kidney with multiple cysts and calcifications; renal teratoma was suspected
      preoperatively, and the operation was performed. The tumor was excised
      completely, and the specimen weighed 340 g. Histopathologic examination showed
      that various teratoid elements occupied most of the tumor with sparse islands of
      triphasic nephroblastoma, which was consistent with teratoid Wilms' tumor.
      Anaplastic elements, tumor capsule invasion, renal sinus soft tissue invasion, or
      tumors in intrarenal vessels were not observed. The patient was disease free for
      3 years after surgery without receiving chemotherapy. We selected this
      therapeutic approach because of the chemoresistance of this tumor and the
      excellent prognosis in small (<550 g) stage I/favorable-histology classical
      Wilms' tumor diagnosed at less than 24 months of age. Therefore, nephrectomy
      alone may be an acceptable treatment of this stage of tumor in patients with
      teratoid Wilms' tumor.

PMID- 17011285
TI  - Recombinant factor VIIa for treatment of massive liver fracture in a premature
      infant.
AB  - Recombinant factor VIIa (rFVIIa) is a highly efficacious therapy initially used
      to treat the bleeding diathesis of hemophiliac patients that has recently gained
      a wider role in the treatment of liver disease, thrombocytopenia, and
      intracerebral and traumatic hemorrhage. Data with regard to the use of rFVIIa
      within the pediatric population for the treatment of liver injury, however, are
      limited. We present a case report of successful treatment using rFVIIa of an
      iatrogenic liver injury in a 1200-g infant who was undergoing resection of a
      large sacrococcygeal teratoma. In addition, we review the issues of surgical
      relevance to the pediatric surgeon relating to rFVIIa's mechanism of action and
      dosages for clinical application.

PMID- 17011286
TI  - Gastrobronchial fistula after toothbrush ingestion.
AB  - Gastrobronchial fistulous communications are uncommon complications of disease
      processes with only 36 previously reported cases. Described as complication of a
      number of conditions, such as previous gastroesophageal surgery, subphrenic
      abscess, and gastric ulcers (Jha P, Deiraniya A, Keeling-Robert C, et al.
      Gastrobronchial fistula--a recent series. Interact Cardiovasc Thorac Sur 2003;2:6
      8), we report a case of fistulization caused by ingestion of a foreign body. A
      patient with mental retardation, admitted for the treatment of osteomyelitis,
      presented during hospitalization symptoms of high fever, vomiting, and
      respiratory distress. Endoscopy showed the presence of a gastrobronchial fistula,
      which developed after ingestion of a toothbrush. The toothbrush was extracted
      endoscopically, and the fistula was subsequently closed by surgery. The patient
      recovered completely. We report the first case of a gastrobronchial fistula as a
      complication of foreign body ingestion.

PMID- 17011287
TI  - Pyloric obstruction, duodenal dilatation, and extrahepatic cholestasis: a
      neonatal triad suggesting multiple intestinal atresias.
AB  - Whereas physiologic jaundice constitutes a common finding in neonates, a few
      cases present with cholestatic jaundice owing to various pathologic conditions,
      including extrahepatic biliary obstruction. We report the case of a 2-day-old
      female neonate presenting with neonatal cholestasis, nonbilious vomiting with
      pyloric obstruction, and multiple intestinal atresias. A pathognomonic
      clinicoradiologic triad is described, based on clinical data, plain abdominal x
      ray, and ultrasound examination.

PMID- 17011288
TI  - Fracture of the occipital condyle caused by minor trauma in child.
AB  - We report a case of fractured occipital condyle caused by minor trauma
      accompanied by light pain on palpation at the lateral cervical trigonum. A 15
      year-old boy complained of nuchal pain, particularly pain on palpation at the
      left lateral cervical trigonum in the absence of neurologic deficits after head
      deceleration trauma. Computed tomography demonstrated a unilateral nonluxated
      fracture of the occipital condyle. Owing to consequent immobilization by means of
      cervical orthosis, pain disappeared after the first 48 hours. Follow-up
      examination 4 weeks later showed no neurologic deficits. The boy had no severe
      impairment of movements at the cervical spine.

PMID- 17011289
TI  - Nonoperative management of omental infarction: a case report in a child.
AB  - Omental infarction is a rare entity in children that is usually diagnosed during
      surgery for suspected appendicitis. We report the clinical case of an obese boy
      presenting with abdominal pain and right-sided tenderness without fever,
      anorexia, or leukocytosis. Abdominal ultrasonography suggested omental
      infarction, and computed tomography confirmed the diagnosis. Nonoperative
      management was adopted with rapid and uneventful recovery. Nonoperative treatment
      of omental infarction is safe and effective; accurate diagnosis is therefore
      crucial to enable a conservative approach. Suggestive clinical features and
      diagnostic workup are addressed.

PMID- 17011290
TI  - Ultrasound-guided basket retrieval of a submandibular duct stone in a child.
AB  - We describe the successful use of ultrasound-guided retrieval of a submandibular
      stone with a basket, in a 13-year-old child.

PMID- 17011291
TI  - Resolution of medically resistant hypothyroidism after liver transplantation for
      hepatic hemangioendothelioma.
AB  - Hepatic hemangioendothelioma (HHE) is a rare vascular tumor in neonates and may
      cause high-output cardiac failure and coagulopathy, and rarely has been
      associated with hypothyroidism. Hepatic hemangioendothelioma treatment options
      consist of corticosteroids, alpha-interferon, surgical resection, and liver
      transplantation. Herein, we report the case of a 6-week-old female neonate that
      presented with an HHE that involved all segments of the liver, resulting in
      respiratory failure and severe hypothyroidism that was recalcitrant to exogenous
      L-thyroxine therapy. After failure of medical and supportive therapy for the HHE,
      the patient underwent a cadaveric orthotopic liver transplantation that resulted
      in successful treatment of the severe hypothyroidism, respiratory failure, and
      cardiac symptoms. The patient is currently 1-year posttransplantation and disease
      free with normal thyroid function.

PMID- 17011292
TI  - Tubularized incised plate repair, also known as the Snodgrass procedure.

PMID- 17011295
TI  - Identification of pepsin in bronchoalveolar fluid (BAL) as a new test for the
      detection of pulmonary aspiration associated with gastroesophageal reflux.

PMID- 17011296
TI  - Delayed presentation of tracheomalacia in an infant with long-gap esophageal
      atresia and distal tracheoesophageal fistula and a right aortic arch.

PMID- 17011306
TI  - The threat to medicine from the cult of irrationality.

PMID- 17011307
TI  - There's many a slip...

PMID- 17011308
TI  - Gastroesophageal reflux: not a time to "relax".

PMID- 17011309
TI  - Hypnosis: an important multifaceted therapy.

PMID- 17011310
TI  - The Apgar challenge.

PMID- 17011311
TI  - Nosocomial rotavirus infections: a systematic review.

PMID- 17011312
TI  - New rotavirus vaccines: renewed optimism.

PMID- 17011313
TI  - Risk factors for intussusception in infants in Vietnam and Australia: adenovirus
      implicated, but not rotavirus.
AB  - OBJECTIVE: This study aimed to investigate risk factors for the development of
      intussusception in infants in a developing country with a suspected high
      incidence and in a developed country with a low incidence. STUDY DESIGN: A
      prospective case-control study of infants <2 years of age with idiopathic
      intussusception confirmed by air enema or surgery was conducted at the National
      Hospital of Paediatrics (NHP), Vietnam (n = 533) and the Royal Children's
      Hospital (RCH), Australia (n = 51). Diagnosis was validated in a subset (84% NHP;
      67% RCH) by an independent blinded radiologist. Risk factor assessment was
      performed using a standardized questionnaire. Stool specimens were assayed for
      bacterial, viral, and parasitic agents. RESULTS: The incidence of intussusception
      in Vietnam was 302/100,000 in infants <1 year of age (95% CI: 258-352),
      substantially higher than in Australia (71/100,000). A strong association with
      adenovirus infection was observed at both sites (cases positive at NHP: 34%, OR
      8.2; cases positive at RCH: 40%, OR 44). No association was identified between
      intussusception and rotavirus, other enteric pathogens, oral polio vaccine,
      feeding practices, or living conditions. CONCLUSIONS: The incidence of
      intussusception in infants was markedly higher in Vietnam than in Australia. A
      strong association between adenovirus infection and intussusception was
      identified at both sites suggesting that adenovirus may play a role in the
      etiology of intussusception.

PMID- 17011314
TI  - Inpatient verbal orders and the impact of computerized provider order entry.
AB  - OBJECTIVE: To describe the characteristics of verbal orders at a tertiary care
      children's hospital. STUDY DESIGN: Between August 2003 and January 2004, the
      computerized provider order entry (CPOE) system was evaluated for the
      characteristics of verbal orders. The rate of total orders represented by verbal
      orders and the rate of unsigned verbal orders were examined before, during, and
      after CPOE implementation. RESULTS: After CPOE implementation, a mean of 19,996
      +/- 521 orders were generated weekly; of these, 2094 +/- 65 (10%) were verbal
      orders. The greatest rates of verbal orders were from psychiatry (74%) units and
      involved medication orders (38%; 790/2094). The greatest rates of medication
      verbal orders were psychotherapeutics (24%; 662/2697). Medical physicians had a
      larger rate of verbal orders than surgical physicians. The rates of verbal orders
      and unsigned verbal orders were reduced from 23% and 43% before CPOE
      implementation to 10% and 9% after implementation, respectively. CONCLUSIONS:
      Medication orders from physicians to nurses are the primary source of verbal
      orders in this tertiary care children's hospital. CPOE implementation
      significantly affected both verbal orders and the rate of unsigned verbal orders.
      This type of data is important for institutions aiming to decrease verbal orders
      and associated medical errors.

PMID- 17011315
TI  - Effect of baclofen on esophagogastric motility and gastroesophageal reflux in
      children with gastroesophageal reflux disease: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of baclofen, a gamma-amino-butyric-acid B
      receptor agonist that inhibits transient lower esophageal sphincter relaxation
      (TLESR), on the rates of TLESR, gastroesophageal reflux (GER), and gastric
      emptying (GE) in children with GER disease. STUDY DESIGN: The efficacy of 0.5
      mg/kg baclofen was evaluated in a randomized, double-blinded, placebo-controlled
      trial in 30 children. Patients were intubated with a manometric/pH assembly and
      given 250 mL of cow's milk. Esophageal motility and pH were then measured for 2
      hours (control period). Baclofen or placebo was then administered, and 1 hour
      later 250 mL of milk was given again and measurements performed for another 2
      hours (test period). The GE rate was measured by the (13)C octanoate breath test.
      RESULTS: Baclofen significantly reduced the incidence of TLESR (mean, 7.3 +/- 1.5
      vs 3.6 +/- 1.2 TLESR/2 hours; P < .05) and acid GER (mean 4.2 +/- 0.7 vs 1.7 +/-
      1.0 TLESR + GER/2 hours; P < .05) during the test period compared with the
      control period. Baclofen significantly accelerated the GE rate (median
      [interquartile range], GE(t1/2), 61 minutes [39, 81 minutes] vs 114 minutes [67,
      170 minutes]; P < .05). Baclofen had no effect on the swallowing rate, pattern of
      esophageal peristalsis, or lower esophageal sphincter pressure. CONCLUSIONS:
      Baclofen reduces GER in children by inhibiting the triggering of TLESR. Baclofen
      also accelerates GE.

PMID- 17011317
TI  - Factors regulating gastric emptying in preterm infants.
AB  - OBJECTIVES: To determine whether osmolality, volume, or energy density affects
      gastric emptying rate (GE); whether simultaneously decreasing osmolality and
      increasing volume accelerates GE; and whether GE is related to any clinical
      and/or demographic characteristics. STUDY DESIGN: GE was measured using the (13)C
      octanoic acid breath test in 17 infants of 25 to 30 weeks gestation in a tertiary
      care children's hospital. In study 1, the independent effects of osmolality,
      volume, and nutrient density were evaluated in 10 infants. In study 2, the
      combined effects of decreasing osmolality and increasing volume were evaluated in
      7 infants. Results from all infants were used to investigate the relationships
      between clinical and demographic characteristics and GE. The statistical analysis
      comprised analysis of covariance, the (paired) Student t-test, the 1-sample
      Wilcoxon test, and regression analysis. RESULTS: Mean (+/- standard deviation)
      age was 27.7 +/- 14.6 days in study 1 and 34.1 +/- 14.0 days in study 2. Altering
      osmolality, volume, or energy density did not change GE, but simultaneously
      decreasing osmolality and increasing feeding volume accelerated GE by 18% versus
      standard feeding. GE correlated with gestational age at birth. CONCLUSIONS:
      Unlike in adults, in preterm infants osmolality, volume, or energy density
      individually do not affect GE. Reducing osmolality and increasing feeding volume
      increases GE. GE is related to gestational age at birth even at age 1 month.

PMID- 17011318
TI  - Polymerase chain reaction diagnosis of primary human herpesvirus-6 infection in
      the acute care setting.
AB  - OBJECTIVE: To evaluate the potential utility of identifying primary human
      herpesvirus (HHV)-6 infection in an emergency department setting by determining
      the frequency of HHV-6 viremia, diagnostic testing, and empiric treatment of
      serious bacterial infection (SBI) in HHV-6 viremic children, and concurrent SBI
      and HHV-6 viremia. STUDY DESIGN: Children under age 2 years and who had a blood
      specimen taken for evaluation of fever were tested for HHV-6 by polymerase chain
      reaction (PCR). HHV-6 viremia was defined as detection of HHV-6 DNA in acute
      plasma. RESULTS: A total of 32 of the 181 subjects (18%) had HHV-6 viremia.
      Children with HHV-6 viremia frequently underwent procedures for diagnosis and
      empiric treatment of SBI: 60% had bladder catheterizations, 6% had lumbar
      punctures, 47% had radiographs, 32% received empiric antibiotics, and 34% were
      hospitalized. Four of the 32 children with HHV-6 viremia (12.5%) were diagnosed
      with SBI, although none had a positive culture of blood or cerebrospinal fluid.
      CONCLUSIONS: Rapid diagnosis of HHV-6 viremia may not serve to adequately
      differentiate infants with and without SBI in acute care settings. Although no
      children with HHV-6 viremia had bacteremia or meningitis, it appears that
      additional criteria are needed to increase the specificity of HHV-6 PCR testing
      before withholding evaluation for SBI.

PMID- 17011319
TI  - Interobserver variability of the 5-minute Apgar score.
AB  - OBJECTIVES: To assess interobserver variability of Apgar scores assigned with
      video recordings of neonatal resuscitation (AS(video)) and compare the scores
      assigned by observers of videos to the Apgar score given by staff attending the
      delivery (AS(del)). STUDY DESIGN: Ten-second clips of 30 newborns taken at 5
      minutes were shown to observers. Infants were 23 to 40 weeks' gestation, received
      varying degrees of resuscitation, and were monitored with pulse oximetry. Forty
      two observers (neonatal/obstetric medical/nursing staff) scored infants'
      respiratory effort, muscle tone, reflex irritability, and color. The value for
      heart rate was assigned from the oximeter, which was masked in all clips. All 42
      AS(video) and the AS(del) were represented graphically for each infant.
      Interobserver reliability was assessed by use of a variance components model.
      RESULTS: AS(video) varied widely between observers. Variability was large for all
      4 elements of the score observers assigned and was seen irrespective of the
      infant's level of illness. AS(del) was greater than AS(video) in most cases, on
      average by 2.4 points. There was no evidence that the level of discrepancy was
      substantially different between groupings of staff. CONCLUSION: The Apgar score
      has poor interobserver reliability. More objective and precise measures of
      newborns' condition are required.

PMID- 17011320
TI  - Cortical recruitment patterns in children born prematurely compared with control
      subjects during a passive listening functional magnetic resonance imaging task.
AB  - OBJECTIVES: To use functional magnetic resonance imaging (fMRI) to test the
      hypothesis that subjects who were born prematurely develop alternative systems
      for processing language. STUDY DESIGN: Subjects who were born prematurely (n =
      14; 600-1250 g birthweight) without neonatal brain injury and 10 matched term
      control subjects were examined with a fMRI passive listening task of language,
      the Clinical Evaluation of Language Fundamentals (CELF) and portions of the
      Comprehensive Test of Phonological Processing (CTOPP). The fMRI task was
      evaluated for both phonologic and semantic processing. RESULTS: Although there
      were differences in CELF scores between the subjects born prematurely and control
      subjects, there were no significant differences in the CTOPP measures in the 2
      groups. fMRI studies demonstrated that the groups differentially engaged neural
      systems known to process language. Children born at term were significantly more
      likely to activate systems for the semantic processing of language, whereas
      subjects born prematurely preferentially engaged regions that subserve phonology.
      CONCLUSIONS: At 12 years of age, children born prematurely and children born at
      term activate neural systems for the auditory processing of language differently.
      Subjects born prematurely engage different networks for phonologic processing;
      this strategy is associated with phonologic language scores that are similar to
      those of control subjects. These biologically based developmental strategies may
      provide the substrate for the improving language skills noted in children who are
      born prematurely.

PMID- 17011321
TI  - Smaller mandibular size in infants with a history of an apparent life-threatening
      event.
AB  - OBJECTIVES: To examine small mandibular size and preference for a hand-to-chin
      posture as salient characteristics in infants with a history of an apparent life
      threatening event (ALTE). STUDY DESIGN: This was a prospective case-control study
      of term infants, from birth to 6 months of age, admitted post-ALTE and matched
      1:2 with healthy control infants (age within 2 weeks and weight within 0.5 kg).
      Infants with confirmed gastroesophageal reflux and congenital anomalies,
      including severe micrognathia, were excluded. RESULTS: Infants with a history of
      an ALTE (n = 25) were matched to 47 healthy controls. Infants with a history of
      an ALTE had mandibular indices (larger index indicates a smaller mandible) that
      were 3.8 mm greater on the left side (95% CI: 2.0-5.6, P < .001) and 4.2 mm
      greater on the right side (95% CI: 2.7-5.6, P < .001) adjusting for length and
      non-white race. Controlling for matching and length, a 1-mm increase in the
      average mandibular index increased the odds of an ALTE by 62% (OR = 1.62, 95% CI:
      1.22-2.44, P < .001). CONCLUSIONS: Smaller mandibular size was associated with
      ALTE, suggesting airway obstruction as a potential cause of ALTE. The association
      of this characteristic with ALTE also offers the potential for prospective
      quantification of ALTE risk.

PMID- 17011324
TI  - Comparison of behavior modification with and without swaddling as interventions
      for excessive crying.
AB  - OBJECTIVE: To test the hypothesis that swaddling is an effective method to reduce
      crying, we compared a standardized approach of regularity and stimulus reduction
      with the same approach supplemented with swaddling. STUDY DESIGN: Healthcare
      nurses coached 398 excessively crying infants up to 12 weeks of age for 3 months.
      Outcome measurements were crying as measured by Barr's 24-hour diary and parental
      perception of crying. RESULTS: Crying decreased by 42% in both groups after the
      first intervention week. Swaddling had no added benefit in the total group. Young
      infants (1-7 weeks of age at randomization) benefited significantly more from
      swaddling as shown by a larger decrease of crying over the total intervention
      period. Older infants (8-13 weeks of age at randomization) showed a significantly
      greater decrease in crying when offered the standardized approach without
      swaddling. The actual difference in crying time was 10 minutes. CONCLUSION: For
      older babies, swaddling did not bring any benefit when added to regularity and
      stimuli reduction in baby care, although swaddling was a beneficial
      supplementation in excessively crying infants <8 weeks of age.

PMID- 17011322
TI  - High prevalence of aeroallergen sensitization among infants of atopic parents.
AB  - OBJECTIVE: To present methodology to identify atopic parents and determine the
      prevalence of sensitization to 15 aeroallergens in their infant offspring. STUDY
      DESIGN: A birth cohort of infants was identified from birth records; an infant
      was enrolled if 1 of the parents reported allergy respiratory symptoms and had a
      positive skin prick test (SPT) to a common aeroallergen. At age 1 year, these
      infants were tested to the same aeroallergens. RESULTS: Of the 680 enrolled
      infants, 28.4% were SPT+ to 1 or more aeroallergens and/or food, and 18.0% were
      positive to 1 or more aeroallergens. By category of allergens, 9.7% were
      sensitized to pollens, 7.5% to molds, 4.3% to house dust mite and/or cockroach,
      and 3.4% to dog and/or cat. Of the infants who were positive to an aeroallergen,
      65.7% remained positive at age 2 years. CONCLUSIONS: Infants born to atopic
      parents with percutaneous sensitization to aeroallergens are at increased risk
      for aeroallergen sensitization during infancy, which persists to age 2 years.
      These findings suggest that current clinical practices, which generally avoid
      skin testing before age 2 years, be reassessed in this population of high-risk
      children.

PMID- 17011325
TI  - The prevalence of overweight and obesity in pediatric survivors of cancer.
AB  - OBJECTIVE: To compare the prevalence of overweight in a cohort of pediatric
      survivors of cancer with that in the general population. STUDY DESIGN: We
      reviewed the charts of 441 cancer survivors followed at a Canadian tertiary care
      pediatric hospital and calculated their most recent body mass index. We compared
      this cohort with population data generated from the Canadian Community Health
      Survey. RESULTS: At a median age of 14.7 years (range, 3.4 to 19.5 years) and a
      median time from diagnosis of 9.7 years (range, 3.4 to 19.2 years), 140 of 441
      patients (31.7%) were overweight or obese. Only 12 of the 441 patients (2.7%)
      were underweight. Males age 6 to 11 years (odds ratio [OR] = 2.29; 95% confidence
      interval [CI] = 1.36 to 3.86; P < .001) and male survivors of acute lymphoblastic
      leukemia (OR = 1.55; 95% CI = 1.03 to 2.52; P = .04) were more likely to be
      overweight than the general population. No other age or diagnostic group had an
      increased risk of overweight. CONCLUSIONS: The prevalence of overweight was not
      increased in this cohort compared with the general population. However, almost
      1/3 of these patients are overweight, necessitating a clinical and research focus
      on preventing and combating overweight in childhood cancer survivors.

PMID- 17011326
TI  - The role of socioeconomic status, depression, quality of life, and glycemic
      control in type 1 diabetes mellitus.
AB  - OBJECTIVE: To test the hypothesis that poor glycemic control in type 1 diabetes
      mellitus (T1DM) is associated with depression and poor quality of life (QOL),
      with a higher prevalence in persons of lower socioeconomic status (SES). STUDY
      DESIGN: Subjects with T1DM age 8 to 17 years (n = 222) were evaluated using the
      Childrens Depression Inventory, the Hollingshead Four-Factor Index to determine
      SES, and PedsQL questionnaires to ascertain QOL. HbAlC > 8% was considered
      indicative of poor glycemic control. RESULTS: A total of 110 well-controlled
      subjects and 112 poorly controlled subjects (HbA1C 7.1% +/- 0.7% vs 9.9% +/-
      1.6%) were recruited. It was found that 9.5% of poorly controlled subjects were
      depressed, compared with 3% of well-controlled subjects. Logistic regression
      revealed a 27% increase in probability of depression per unit rise in HbA1C (P <
      .03). Higher SES was associated with better glycemic control (P < .0005) and QOL
      (P < .0005); longer duration of illness was not associated with poorer glycemic
      control. Diabetes QOL deteriorated with poorer glycemic control (P < .002).
      CONCLUSIONS: Poor glycemic control in peridatric T1DM is associated with lower
      SES and depression. The probability of depression increases as glycemic control
      worsens. Screening for depression should be routinely carried out in patients
      with T1DM, targeting patients with deteriorating glycemic control.

PMID- 17011327
TI  - Reproductive outcome in patients treated and not treated for idiopathic early
      puberty: long-term results of a randomized trial in adults.
AB  - OBJECTIVE: To evaluate the adult reproductive outcome in girls with early puberty
      who participated in a previous random study. STUDY DESIGN: A total of 22 subjects
      treated with triptorelin 3.75 mg every 4 weeks (group 1), 18 subjects not treated
      (group 2), and 22 age-matched normal volunteers (control group) underwent a
      physical examination, serum hormone level determination, and pelvic
      ultrasonography. RESULTS: The characteristics of menstrual cycles, serum hormone
      levels, and ultrasound results did not differ significantly among the 3 groups
      examined. The mean ovarian volume and the uterine volume tended to increase in
      the subjects of group 2, but the differences were not significant. The percentage
      of subjects who reported being sexually active at the time of the examination was
      greater in the 2 groups with previous early puberty than in the controls (76% of
      cases in group 1, 72% in group 2, and 59% in the control group). CONCLUSIONS:
      Neither early puberty nor its treatment seems to significantly affect the normal
      adult function of the pituitary-gonadal axis.

PMID- 17011328
TI  - Venous thrombosis and thromboembolism in children with osteomyelitis.
AB  - OBJECTIVE: To determine the prevalence and clinical features of deep vein
      thrombosis (DVT) complicating osteomyelitis during childhood. STUDY DESIGN: We
      retrospectively reviewed medical records of all patients with osteomyelitis
      admitted to Children's Medical Center Dallas between July 1, 2003 and December
      31, 2004. Analysis was performed on patients with proximal upper or lower
      extremity, pelvic or vertebral osteomyelitis (a subgroup considered to be at
      highest risk for infection-related thrombosis). RESULTS: Thirty-five patients had
      confirmed osteomyelitis of the proximal humerus, proximal tibia/fibula, femur,
      pelvis, or vertebrae. Ten of these 35 children (29%) developed DVT during the
      acute infection based on imaging studies performed. Eight thrombi occurred
      adjacent to the infection and two occurred in relation to central venous
      catheters. Six of the 10 children with DVT also had evidence of infection
      disseminated to lung, brain, or heart, compared with only 1 of 25 patients
      without DVT (P = .001). Hospitalization was longer in those with DVT than without
      (33.5 v. 14.2 days, P = .001). CONCLUSION: Thromboembolic complications can occur
      in the setting of osteomyelitis, and affected patients may be at higher risk of
      disseminated infection.

PMID- 17011329
TI  - Predictors of seizure onset in Rett syndrome.
AB  - OBJECTIVES: To investigate risk factors for seizure onset in Rett syndrome. STUDY
      DESIGN: Information on presence and age at onset of seizures, perinatal and
      developmental history, and genetic status was abstracted on 275 cases in the
      Australian Rett Syndrome Database. Cox and Weibull regression were used to
      investigate and provide a model for predicting the effects of genetic and
      developmental factors on age at seizure onset. RESULTS: Seizures were reported in
      81% of 275 cases; the median age of onset was 48 months. Not having gained the
      ability to walk (P = .003) and developmental problems in the first 10 months of
      age (P = .04) were associated with an almost 2-fold increased risk of seizures.
      Cases without a detectable MECP2 mutation had a higher risk of seizure onset up
      to 4 years of age (P < .001) but a lower risk after 4 years (P = .08).
      CONCLUSIONS: Seizure onset in Rett syndrome is associated with early
      developmental factors and with genotype. Information on these factors can be used
      to predict age at seizure onset after diagnosis.

PMID- 17011330
TI  - Long-term outcomes after infant lung transplantation for surfactant protein B
      deficiency related to other causes of respiratory failure.
AB  - OBJECTIVE: To determine if the outcomes of lung transplantation for infants with
      surfactant protein-B (SP-B) deficiency are unique. STUDY DESIGN: From a
      prospective analysis to identify infants with genetic causes of surfactant
      deficiency, we identified 33 SP-B-deficient infants from 1993 to 2005, and, among
      those undergoing lung transplantation (n = 13), compared their survival,
      pulmonary function, and developmental progress with infants who underwent
      transplantation at <1 year of age for parenchymal lung disease (n = 13) or
      pulmonary vascular disease (n = 11). RESULTS: Five-year survival rates (
      approximately 50%, P = .3) and causes of death were similar for all three groups
      once the infants underwent transplantation. However, significant
      pretransplantation mortality decreased 5-year survival from listing to
      approximately 30% (P = .17). Pulmonary function, development of bronchiolitis
      obliterans, and school readiness were similar among the three groups. We detected
      anti SP-B antibody in serum of 3 of 7 SP-B-deficient infants and none of 7 SP-B
      sufficient infants but could not identify any associated adverse outcomes.
      CONCLUSIONS: Long-term outcomes after infant lung transplantation for SP-B
      deficient infants are similar to those of infants transplanted for other
      indications. These outcomes are important considerations in deciding to pursue
      lung transplantation for infants with disorders of alveolar homeostasis.

PMID- 17011332
TI  - Acid sphingomyelinase deficiency: prevalence and characterization of an
      intermediate phenotype of Niemann-Pick disease.
AB  - OBJECTIVE: To document the prevalence of neurologic disease in Niemann-Pick
      disease (NPD) NPD-B. STUDY DESIGN: Sixty-four patients with NPD-B had detailed
      neurologic and ophthalmologic evaluations. The presence of neurologic
      abnormalities was compared with genotype. RESULTS: Nineteen of 64 patients (30%)
      had neurologic abnormalities, which were minor and nonprogressive in 14 (22%),
      and global and progressive in 5 (8%). In these five patients, the onset of
      neurologic difficulties occurred between 2 and 7 years of age and was associated
      with peripheral neuropathy, retinal abnormalities, and the Q292K mutation. No
      patients with at least one copy of DeltaR608 had neurologic involvement.
      CONCLUSIONS: The majority of patients with NPD-B have no neurologic
      abnormalities. In patients with neurologic abnormalities, the findings can be
      minor and static or severe and progressive. The latter phenotype follows a course
      distinct from that of classic NPD-A and is associated with the Q292K mutation and
      characteristic retinal findings. Thus, similar to other lysosomal storage
      disorders, there is a broad spectrum of neurologic abnormalities in acid
      sphingomyelinase deficiency, which makes the current classification scheme
      inaccurate.

PMID- 17011333
TI  - Pediatric workforce: a look at pediatric gastroenterology data from the American
      Board of Pediatrics.

PMID- 17011334
TI  - Clinical hypnosis as an effective adjunct in the care of pediatric inpatients.
AB  - Clinical hypnosis is an established part of the comprehensive treatment of
      numerous problems in ambulatory pediatrics. Two cases illustrate its utility with
      pediatric inpatients. These cases demonstrate clinical hypnosis as a teachable,
      practical, and nonpharmacologic intervention that warrants further investigation
      in the inpatient setting.

PMID- 17011335
TI  - Hypothyroidism in a breast-fed preterm infant resulting from maternal topical
      iodine exposure.
AB  - Hypothyroidism developed in a preterm infant, whose initial screening thyroid
      function test results were normal, at 2 weeks of life. The infant's mother was
      packing her Caesarian incision with iodine soaked gauze, resulting in a markedly
      increased breast milk iodine concentration. Treatment with oral L-thyroxine
      normalized thyroid function tests.

PMID- 17011336
TI  - Compliance with guidelines for ADHD: a pilot study of an evaluation tool.
AB  - The investigators developed a 1-page chart abstraction tool to evaluate
      compliance with practice guidelines for attention deficit hyperactivity disorder.
      The tool had strong inter-rater reliability, with kappa of 0.81. Pilot testing
      for 57 children with attention deficit hyperactivity disorder showed only 12%
      documented full compliance with assessment guidelines and 44% with treatment
      guidelines.

PMID- 17011337
TI  - Adalimumab therapy for childhood uveitis.
AB  - Fourteen children with uveitis (9 JIA associated and 5 idiopathic) were treated
      with adalimumab for an average of 18.1 months. Inflammation decreased in 21/26
      eyes (80.8%), 4 eyes remained stable (15.4%), and 1 worsened (3.8%) (P < .001; 2
      tailed paired Wilcoxon rank sum test). No significant adverse events occurred.

PMID- 17011338
TI  - A vertebro-vertebral fistula as a complication of a jugular line.

PMID- 17011339
TI  - Skull mass as a heralding sign of precursor B-cell acute lymphoblastic leukemia
      in a toddler.

PMID- 17011340
TI  - Gene polymorphisms and bronchopulmonary dysplasia.

PMID- 17011342
TI  - Re: Deletion allele of angiotensin-converting enzyme.

PMID- 17011343
TI  - Fluid supplementation for neonatal hyperbilerubinemia.

PMID- 17011345
TI  - Re: Randomized controlled trial of fluid supplementation in term neonates with
      severe hyperbilirubinemia.

PMID- 17011346
TI  - Pediatricians' IQ on RDS, NAFLD, and syndrome X.

PMID- 17011348
TI  - Plagiarism: digging to the root of the problem.

PMID- 17011349
TI  - Living with endometriosis: the perspective of male partners.
AB  - OBJECTIVE: The purpose of this qualitative study was to explore the experiences
      of partners of women with endometriosis. METHODS: Sixteen male partners completed
      questionnaires pertaining to the impact of endometriosis. Three male partners
      participated in additional semistructured interviews. RESULTS: Thematic analysis
      of combined questionnaire and interview data revealed several common emotional
      themes relating to living with endometriosis. These strong emotions included low
      mood, anxiety, and powerlessness and contributed to a grief-like process much
      like that experienced by their female partners, with some also reporting
      acceptance and relationship growth. The clinical significance of these findings
      for systemically effective management of endometriosis will be discussed.

PMID- 17011350
TI  - Knowledge and expectation of postconcussion symptoms in the general population.
AB  - OBJECTIVE: Beliefs about mild traumatic brain injury (MTBI) may affect complaints
      and their persistence. This study investigates the relationships between
      knowledge, experience, and expectation in the general population. METHODS: One
      hundred seventy-one people reported symptoms expected from vignettes about MTBI,
      depression, posttraumatic stress disorder (PTSD), and orthopedic injury. Then
      they completed a postconcussional syndrome (PCS) checklist about these vignettes
      and about personal symptoms. RESULTS: The ability to generate symptoms from
      vignettes was poor for PCS, depression, and PTSD, and was greatly improved using
      a PCS checklist, probably by symptom guessing. No postconcussion symptoms were
      associated specifically with MTBI. Those with more personal symptoms expected
      more symptoms. Past experience of MTBI did not improve symptom knowledge. Beliefs
      about the 'undesirability' of conditions were associated with expected outcomes.
      CONCLUSIONS: People know little about PCS. Expectations about MTBI are influenced
      by psychological factors that are relevant if we consider information given in
      hospitals. Symptom overlap means that psychological conditions such as depression
      may be misdiagnosed as PCS, and checklists should not be used for diagnosis.

PMID- 17011351
TI  - Accompanying symptoms and psychiatric comorbidity in migraine and tension-type
      headache patients.
AB  - OBJECTIVE: Our objective was to assess the prevalence of accompanying symptoms of
      migraine and tension-type headache in patients with such conditions (both
      episodic and chronic) and in headache-free controls, and their relationship with
      depression and anxiety. METHOD: A psychological assessment (Axis I, DSM-IV) was
      performed, and 21 accompanying symptoms were investigated in 506 patients with
      episodic migraine (231), chronic migraine (102), episodic tension-type headache
      (83), and chronic tension-type headache (90) and in 80 controls. The relationship
      between symptoms, headache type, and psychiatric comorbidity was analyzed.
      RESULTS: The mean number of symptoms was significantly higher in patients
      (n=10.3) than in controls (n=3.4). Most symptoms were significantly associated
      with depression and anxiety, while only some of them were significantly
      associated with headache, with no relevant difference among groups. CONCLUSION:
      In headache patients, psychiatric comorbidity (compared with headache type or
      chronicity) seems to be more strictly associated with an increased burden of
      accompanying symptoms.

PMID- 17011352
TI  - Effects of corticotropin-releasing hormone (CRH) on endothelin-1 and NO release,
      mediated by CRH receptor subtype R2: a potential link between stress and
      endothelial dysfunction?
AB  - OBJECTIVE: Psychosocial factors, associated with elevated corticotropin releasing
      hormone (CRH) concentrations, have been reported to be independently associated
      with coronary heart disease. METHODS: Endothelin-1 and NO release of human
      endothelial cells were quantified via ELISA or fluorometrically after treatment
      with CRH. CRH-receptor subtype 2 (CRH-R2) was visualized on endothelial cells by
      immunohistochemistry and confirmed by polymerase chain reaction using CRH-R2
      primers. RESULTS: CRH induced a significant increase of ET-1 release, and the
      effect was abolished by the CRH-receptor antagonist astressin. The effect was
      mediated by CRH-R2. In contrast, NO release was not affected. CONCLUSION: CRH-R2
      is expressed on human endothelial cells, mediating the CRH-induced stimulation of
      ET-1 release, whereas NO release is not affected. Thus, peripherally circulating
      CRH may offset the balance between endothelial vasoconstrictor and vasodilator
      release with unopposed vasoconstriction. Our data may provide a new concept on
      how CRH-receptor antagonists may prevent CRH-induced disorders of vascular
      biology.

PMID- 17011353
TI  - A single session of reassurance can acutely improve the self-perception of
      impairment in patients with IBS.
AB  - OBJECTIVE: The aim of this study was to determine the reported frequency and self
      perceived importance of factors related to health care seeking by irritable bowel
      syndrome (IBS) patients and the effect of reassurance on these factors. METHODS:
      Fifty-five IBS patients, consulting for the first time, answered a questionnaire
      designed to evaluate these factors (FRQ), measurements of anxiety, depression,
      and quality of life (QoL). A thorough explanation of the disease and reassurance
      were given, and the FRQ was answered again. RESULTS: The frequency of factors
      was: pain/discomfort, 78%; cancer fear, 11%; daily function impairment, 33%;
      symptoms stressfulness, 60%; and none, 2%. Pain/discomfort and symptom
      stressfulness were considered the most important ones. Cancer fear and symptom
      stressfulness correlated with anxiety (P=.003, .042), depression (P=.038, .019),
      and daily function impairment with depression (P=.05). Cancer fear, daily
      function impairment, and symptom stressfulness impacted on QoL. Reassurance
      acutely decreased the self-perception of daily function impairment (P=.003),
      independent of the patient's educational level. CONCLUSIONS: Reassurance during
      the first consultation for IBS decreased the self-perception of impairment in
      daily function.

PMID- 17011354
TI  - Translation and validation of the Chinese version of the Gastrointestinal Quality
      of Life Index in patients with gastric tumor.
AB  - OBJECTIVE: Patients with gastric tumor are known to have deterioration in quality
      of life (QOL) following surgery. However, there is no valid disease-specific self
      report QOL measure for clinical practice and research designated for Chinese in
      Hong Kong. The current study aimed at translating and validating a Chinese
      version of the Gastrointestinal Quality of Life Index (C-GIQLI) for use in
      patients with gastric tumors after gastrectomy. METHODS: A translation of the
      English version of the instrument was performed. The psychometric properties of
      the C-GIQLI were investigated using internal consistency analysis, correlational
      analysis, and confirmatory factor analysis in 140 Chinese patients who had
      undergone surgery for gastric tumor. RESULTS: The C-GIQLI demonstrated good test
      retest reliability, internal consistency, and a factor structure consistent with
      the measurement model of the European version of the instrument. CONCLUSION: The
      C-GIQLI is recommended as a valid and reliable self-report measure of QOL in
      patients with gastric tumor after gastrectomy.

PMID- 17011355
TI  - Persistence of psychiatric disorders in a cohort of HIV/AIDS patients in South
      Africa: a 6-month follow-up study.
AB  - BACKGROUND: Psychiatric disorders in HIV/AIDS are common, emerging soon after
      diagnosis or during the subsequent course of illness. However, there are few
      prospective studies on the rates of psychiatric disorders in HIV/AIDS,
      particularly in the context of the developing world. METHODS: Sixty-five patients
      with recently diagnosed HIV were interviewed on presentation to a hospital-based
      HIV clinic and then 6 months later. On both interviews, the patients were
      assessed using the MINI International Neuropsychiatric Interview, the Carver
      Brief COPE, and the Sheehan Disability Scale. Exposure to negative life events
      and risk behaviors was also evaluated. RESULTS: The overall prevalence of
      psychiatric disorders in the follow-up period remained high (56% of patients had
      at least one psychiatric disorder at baseline, and 48% of patients had at least
      one psychiatric disorder at 6 months). Depression and posttraumatic stress
      disorder (PTSD) were the most prevalent disorders at both baseline (34.9% and
      14.8%) and follow-up (26% and 20%), respectively. More than half of all patients
      with depression at baseline improved (16 of 29; 55.1%). However, there was a new
      onset of both depression (4 of 49; 8.1%) and PTSD (12 of 17; 70.5%) on follow-up.
      In univariate analysis, depression on follow-up was significantly associated
      with: (a) disability in work/social/family functioning, (b) greater number of
      negative life events, and (c) a decline in CD4 lymphocyte count. Univariate
      analysis also revealed that a diagnosis of PTSD on follow-up was significantly
      associated with (a) a longer duration of infection and (b) baseline disability in
      work/social/family functioning. However, in multivariate analysis, only
      disability scores predicted the diagnoses of major depression and PTSD on follow
      up assessment. Persistence of risky sexual behaviour was also noted, with a
      significantly higher number of participants reporting nonuse of condom on follow
      up. There appeared to be a shift from maladaptive coping behaviors to more
      adaptive coping behaviors over the 6-month period. CONCLUSION: The rate of
      psychiatric disorders in HIV/AIDS patients was consistent over time. These
      findings emphasize the importance of regular evaluation for psychiatric disorders
      in HIV/AIDS patients, not only at the commencement of treatment but also during
      subsequent follow-up visits.

PMID- 17011356
TI  - Self-care behavior, hope, and social support in Taiwanese patients awaiting heart
      transplantation.
AB  - OBJECTIVE: The purpose of this study was to examine the self-care behavior, hope,
      and social support in patients awaiting heart transplantation and to explore all
      the correlative and related factors. METHODS: In total, 45 participants who met
      the selection criteria were selected by purposive sampling from four medical
      centers in Taiwan. The three instruments Self-Care Behavior Scale, Herth Hope
      Index (HHI), and Social Support Inventory were used for data collection. RESULTS:
      Significant, positive correlations among self-care behavior, hope, and social
      support were observed. Social support was the best predictive factor for both
      self-care behavior and hope. CONCLUSION: The outcomes of this study can help
      medical care personnel better understand the self-care behavior, hope, and social
      support in patients awaiting heart transplantation and can also serve as a
      reference when developing relevant interventions for these patients.

PMID- 17011357
TI  - Decreased impact of post-myocardial infarction depression on cardiac prognosis?
AB  - OBJECTIVE: A recent meta-analysis suggests that the impact of post-myocardial
      infarction (MI) depression on cardiac prognosis has decreased over the last
      decade. We tested whether depression still significantly affects prognosis in the
      present health care situation. METHODS: Four hundred ninety-four MI patients were
      screened for depression. Patients with depression were compared with patients
      without on cardiovascular events (fatal or nonfatal) during an average follow-up
      of 2.5 years. Demographic characteristics and cardiac risk factors were
      controlled for. RESULTS: We found that depression was associated with the
      occurrence of cardiovascular events in both univariate [hazard ratio (HR), 1.84;
      95% confidence interval, 1.24-2.72] and multivariate analysis (HR, 1.56; 1.02
      2.38). CONCLUSIONS: Depression still has an independent impact on cardiac
      prognosis after MI, but this influence is smaller than found in early studies.
      Improvements in general care for MI and better recognition and treatment of post
      MI depression may have decreased the impact of depression on prognosis.

PMID- 17011358
TI  - Body esteem as a moderator of cardiovascular stress responses in anatomy students
      viewing cadaver dissections.
AB  - OBJECTIVE: Anatomy training requires students to take courses involving the
      dissection of human cadavers. It is suspected that such tuition is stressful for
      some students more than for others. Terror management theory suggests that the
      mortality salience presented by cadaver dissections would heighten stress among
      those students with positive self-images. The present study sought to investigate
      the association between body esteem (BE) and cardiovascular stress reactivity to
      cadaver dissections. METHODS: The study involved the measurement of
      cardiovascular stress responses in 36 anatomy students during a dissection class.
      Psychometric assessments of BE and other variables were taken. RESULTS: Students
      with high BE had lower heart rate (P=.011) and exhibited greater decreases in
      systolic blood pressure (P=.008) and pulse pressure (P=.003) throughout the
      session, suggestive of maladaptive stress response. CONCLUSIONS: As findings are
      consistent with theories linking BE with stress in occupations that require
      workers to view dead bodies, the consideration of BE may be an effective
      component in stress reduction interventions.

PMID- 17011359
TI  - Bioenergetic exercises in inpatient treatment of Turkish immigrants with chronic
      somatoform disorders: a randomized, controlled study.
AB  - OBJECTIVE: The aim of this study was to examine whether bioenergetic exercises
      (BE) significantly influence the inpatient psychotherapeutic treatment results
      for Turkish immigrants with chronic somatoform disorders. METHOD: In a 6-week
      randomized, prospective, controlled trial, we treated a sample of 128 Turkish
      patients: 64 were randomly assigned to BE and 64 participated in gymnastic
      exercises in lieu of BE. The Symptom Checklist (SCL-90-R) and State-Trait Anger
      Expression Inventory (STAXI) were employed. RESULTS: According to the intent-to
      treat principle, the bioenergetic analysis group achieved significantly better
      treatment results on most of the SCL-90-R and STAXI scales. CONCLUSIONS: BE
      appears to improve symptoms of somatization, social insecurity, depressiveness,
      anxiety, and hostility in the inpatient therapy of subjects with chronic
      somatoform disorders. Reduction of the anger level and reduction in directing
      anger inwards, with a simultaneous increase of spontaneous outward emotional
      expression, could be expected.

PMID- 17011360
TI  - Relations of physical self-concept and self-efficacy with frequency of voluntary
      physical activity in preadolescents: implications for after-school care
      programming.
AB  - OBJECTIVE: This study aimed to test relations of physical self-concept and self
      efficacy with voluntary physical activity in preadolescents enrolled in an after
      school physical activity program. METHODS: Participants in the 2003 (n=41) and
      2005 (n=84) versions of the Youth Fit For Life protocol and the control group
      (n=40) completed the Physical Self-Concept scale, the Exercise Barriers Self
      Efficacy Scale for Children, and a recall of physical activity frequency at Weeks
      1 and 12. RESULTS: Both treatment groups demonstrated significantly increased
      frequency of voluntary physical activity over 12 weeks. The 2005 version
      additionally demonstrated significant improvements in both physical self-concept
      and exercise barriers self-efficacy. Within the treatment groups, significant
      correlations between changes in physical self-concept and self-efficacy and
      physical activity sessions completed were found. Multiple regression indicated
      that 7% to 28% of the variance in voluntary physical activity was explained by
      the simultaneous entry of changes in physical self-concept and self-efficacy.
      CONCLUSION: Tenets of social cognitive and self-efficacy theory were supported
      and suggested that curricular elements of after-school care programming may
      increase overall outputs of moderate-to-vigorous physical activity in
      preadolescents.

PMID- 17011361
TI  - Five-year change in body satisfaction among adolescents.
AB  - OBJECTIVE: The present study uses longitudinal data to examine changes in body
      satisfaction among male and female adolescents from baseline to 5 years. METHODS:
      A diverse sample of 2,516 adolescents completed surveys in 1999 and 2004,
      reporting satisfaction with 10 body parts or attributes, height/weight, and other
      characteristics. Multivariable general linear modeling was used to estimate
      change in body satisfaction from Time 1 to Time 2, by age group, race, and change
      in body mass index (BMI) category. RESULTS: Body satisfaction decreased over 5
      years (mean satisfaction change=-0.79) in all groups except older adolescent
      females. Scores decreased significantly more among younger adolescents than older
      adolescents, among some racial/ethnic groups of males, and among those whose BMI
      increased. However, among males, change in body satisfaction depended on BMI
      category at baseline. CONCLUSIONS: Different types of prevention programs
      addressing body image may be needed for males and females at different
      developmental stages and may need to address changes in BMI.

PMID- 17011362
TI  - Gender role, eating disorder symptoms, and body image concern in ballet dancers.
AB  - OBJECTIVE: Our objective was to evaluate the relationships between gender role,
      eating behavior, and body image in nonprofessional female ballet dancers.
      METHODS: One hundred ten female ballet dancers and 59 controls were administered
      the Bem Sex Role Inventory, the Eating Disorder Examination (EDE), the Body
      Uneasiness Test (BUT), and the Beck Depression Inventory. RESULTS: Ballet dancers
      scored higher than controls in most of the items evaluating body image and eating
      behaviors; a high number of ballet dancers with undifferentiated gender role were
      also observed. In the dancers group, male-typified subjects showed higher median
      scores of EDE and BUT scales, while in the control group, the highest median
      scores of EDE and BUT scales were found in undifferentiated subjects. CONCLUSION:
      Ballet schools' cultural pressure towards an ideal of leanness could interfere
      with the process of gender role acquisition. Ballet dancers appear to be
      overconcerned with performance; this could reinforce the internalization of
      several constructs that are generally considered as typically male.

PMID- 17011363
TI  - Autobiographical memory deficit in anorexia nervosa: emotion regulation and
      effect of duration of illness.
AB  - Emotional deficits in anorexia nervosa can be expressed in autobiographical
      memory recall. The aim of this study is to test whether deficits in
      autobiographical memory exist in anorexic patients and concern specifically
      negative or positive emotional valence. Moreover, it is unclear whether these
      deficits are dependent upon comorbid aspects (depression, alexithymia, and
      anxiety) or upon illness duration. Anorexic patients (n=25) were compared to
      healthy volunteers based on their clinical assessment, explicit memory test
      score, and autobiographical memory test score. The study makes use of the
      autobiographical test of Williams and Scott, which involves specific emotional
      cues to elicit memory. Anorexic patients recalled more general memories than
      controls in autobiographical memory test, but had no deficit in explicit memory
      test. This pattern, observed both for negative and positive cues, was neither
      related to depression or alexithymia, nor to anxiety severity, but increased
      significantly with illness duration. These results show that anorexic patients
      are characterized by relative difficulty in the integration of both negative and
      positive emotional experiences, and that this impairment is reinforced by illness
      duration.

PMID- 17011364
TI  - Adherence, behavior change, and visualization: a qualitative study of the
      experiences of taking an obesity medication.
AB  - OBJECTIVE: Our objective was to examine patients' experiences of taking orlistat
      as a means to explore adherence and behavior change. METHOD: We performed
      qualitative interviews with 12 participants who had taken orlistat in the past 2
      years. RESULTS: Their experiences were described in terms of beliefs about the
      causes of their obesity, their motivations for taking orlistat, and highly visual
      side effects. These themes have implications for understanding adherence and
      behavior change. For some, the side effects led to nonadherence and absence of
      behavior change. These individuals seemed to be motivated by routine effects of
      being overweight, such as lowered self-esteem. In contrast, those who were
      motivated by a life crisis seemed to tolerate the side effects of the drug,
      leading to adherence. In turn, these highly visual side effects enabled them to
      make an explicit link between food consumed and weight, creating a shift in their
      beliefs about the causes of obesity and making behavior change more likely.
      CONCLUSION: Orlistat use illustrates how treatment and illness beliefs interact
      to create both adherence and behavior change, particularly in the context of a
      life crisis and particularly when symptoms can be visualized.

PMID- 17011365
TI  - Use of medical doctors, physical therapists, and alternative practitioners by
      obese adults: does body weight dissatisfaction mediate extant associations?
AB  - OBJECTIVE: The objective of this study was to assess the association of obesity
      with the utilization of general practitioners (GP), medical specialists (MS),
      physical therapists (PT), and alternative practitioners (AP), and to elucidate
      whether body weight dissatisfaction mediates extant associations. METHODS: In an
      adult population survey (KORA Survey S4 1999/2001) in Augsburg, Germany,
      anthropometric body mass [body mass index (BMI), kg/m(2)], utilization, physical
      comorbidities, functional limitations due to body weight, and body weight
      dissatisfaction were assessed and analyzed via multiple logistic regressions.
      RESULTS: Obese adults (BMI>or=30) had around double odds of AP, GP, and PT
      utilization. Regarding AP and, to a lesser extent, PT, body weight
      dissatisfaction both had direct effects and mediated excess utilization. Most
      notably, the odds for AP use were about twofold in those who were dissatisfied,
      and the association of obesity and AP use diminished when adjustment for
      dissatisfaction was performed. Among overweight participants (25<or=BMI<30), only
      PT use was elevated and tended to be mediated by dissatisfaction as well.
      CONCLUSION: Body weight dissatisfaction mediates obesity-attributable utilization
      of nonmedical health care providers, especially AP. Possibly, dissatisfaction
      leads to demands for psychosocial care that is expected to be offered by
      complementary and allied health professions. For health services utilization
      research, results call for a scrutiny of body weight dissatisfaction-a known
      barrier to adopting long-term healthy lifestyles. For practice, results indicate
      that AP and PT may have special opportunities to encourage the use of preventive
      services by obese adults.

PMID- 17011366
TI  - Body of evidence: tattoos, body piercing, and eating disorder symptoms among
      adolescents.
AB  - OBJECTIVE: Tattoos and body piercing have been linked to risk-taking behaviors,
      including disordered eating, but the findings have come from selected samples
      that were at greater risk for bias due to comorbidity. This study set out to
      explore concurrently the prevalence of tattoos and body piercing, and eating
      disorder symptoms in a representative adolescent sample of a community in
      Sardinia, a major island in Italy. METHODS: A community sample of 828 students
      (female, 535; male, 282; mean age=17.5+/-1.4 years) among those attending high
      school in the district of Cagliari, Italy, were invited to take the Eating
      Attitudes Test, the Bulimic Investigatory Test of Edinburgh, and the Body
      Attitudes Test, alongside a short questionnaire aimed at evaluating their
      resorting to body modification practices, including tattooing and body piercing.
      RESULTS: Females scored higher than males at all eating disorder inventories.
      More males than females admitted the use of tattoos (14.5% vs. 5.4%), whereas the
      reverse was found for body piercing (18.4% vs. 21.3%). Tattoos among females and
      body piercing in both genders were statistically associated with eating disorder
      measures related to bulimia symptoms. On the whole, the degree of association was
      modest. CONCLUSIONS: Tattoos and body piecing should be seen as desires to show a
      subject's identity rather than as a marker of psychopathology. Greater health
      education, however, is needed in the wake of the growing popularity of these body
      modification practices.

PMID- 17011367
TI  - Test-retest reliability of the Eating Disorder Inventory 2.
AB  - OBJECTIVE: This study reports on findings concerning the test-retest reliability
      of the Eating Disorder Inventory 2 (EDI-2). METHODS: Three hundred twenty-seven
      female inpatients who met the DSM-IV criteria for eating disorders (anorexia
      nervosa, bulimia nervosa, or eating disorders not otherwise specified) and 209
      inpatients with a diagnosis of depression, obsessive-compulsive disorder, anxiety
      disorder, or somatoform disorder took part in the study. The EDI-2 was
      administered to the patients at the beginning of inpatient therapy and a second
      time 7 days later. RESULTS: All 11 EDI-2 subscales showed significant test-retest
      correlations ranging from .81 to .89 in the eating disorder group and from .75 to
      .94 in the group with other diagnoses. DISCUSSION: The test-retest reliabilities
      for the EDI-2 subscales are relatively high, indicating a good and acceptable
      stability over time. These results provide further evidence that the EDI-2 is an
      instrument with good reliability for the assessment of eating disorder symptoms.

PMID- 17011368
TI  - Changes in heart rate with refeeding in anorexia nervosa: a pilot study.
AB  - OBJECTIVE: To find differences in heart rate before and after refeeding and to
      identify which parameters of autonomic activity and endocrine function are
      associated with these differences. METHODS: Before and after the start of
      refeeding, body weight, RR interval (RRI), heart rate variability, endocrine
      function, and energy expenditure were measured in nine female anorexia nervosa
      patients. RESULTS: After short-term refeeding, mean daytime heart rate rose from
      54.9 to 69.4 bpm (P<.05). The changes in sympathetic activity were correlated
      negatively with the changes in RRI (r=-.933, P<.001). Urine C-peptide, IGF-1, and
      fT3 increased significantly, and norepinephrine tended to increase. CONCLUSION:
      We demonstrated that autonomic nervous activity was relevant to changes in heart
      rate during refeeding, and it is speculated that the increases in insulin
      secretion, thyroid function, and IGF-1 were responsible for the mechanisms.

PMID- 17011371
TI  - Research instruments for the diagnosis and treatment of patients with erectile
      dysfunction.
AB  - As the incidence and prevalence of erectile dysfunction (ED) increase, healthcare
      providers will require robust, accurate, and efficient tools for appropriately
      diagnosing and treating patients with ED. Moreover, clinicians will need
      effective follow-up tools that assess treatment efficacy and satisfaction, to
      help patients meet their expectations for successful treatment of ED. We provide
      a summary of some of the most commonly used instruments for the diagnosis and
      assessment of ED treatment efficacy that will be referred to in this supplement.

PMID- 17011372
TI  - Erection hardness: a unifying factor for defining response in the treatment of
      erectile dysfunction.
AB  - The extensive sildenafil citrate erectile dysfunction (ED) database of double
      blind, placebo-controlled clinical trials was examined to determine the relation
      between erection hardness graded on the Erectile Hardness Grading Scale (EHGS)
      and (1) erectile function (EF), as assessed by the EF domain of the International
      Index of Erectile Function (IIEF); (2) frequency of erections hard enough for
      penetration, as assessed by IIEF Q2; and (3) the percentage of successful sexual
      intercourse attempts according to patient event logs. Pooled data from 6549 men
      with ED provided strong proof and improved characterization of the response to
      sildenafil. Almost half of men with ED and a baseline IIEF EF domain score
      classified as "severe ED" (< or = 10) shifted to a score classified as "no ED" (>
      or = 26). Sildenafil recipients showed greater mean improvement from baseline to
      end point in IIEF Q2 scores versus placebo, regardless of baseline ED severity,
      and a higher mean percentage of successful sexual intercourse attempts occurred
      during the last 4 weeks of treatment versus placebo (5.4-fold vs 2.0-fold
      increase from baseline). At end point, 95% of men who scored "no ED" on the IIEF
      EF domain and 92% of men who reported "almost always/always" achieving an
      erection hard enough for penetration (IIEF Q2) had graded their erections hard
      (rigid) enough for penetration (grade 3) or completely hard and fully rigid
      (grade 4) during the last 4 weeks of treatment, suggesting that the IIEF EF
      domain and IIEF Q2 may be good surrogate end points for erection hardness.
      Furthermore, during the last 4 weeks of treatment, the percentage of grade 3
      and/or 4 erections correlated positively with the percentage of successful sexual
      intercourse attempts. Hence, hard erections may be considered a unifying factor
      that defines response to ED treatment. Completely hard and fully rigid erections
      (grade 4) should be recognized as the optimal goal of an ED therapy. Evidence
      presented here demonstrates that sildenafil significantly improved EF as assessed
      by the IIEF EF domain and assessments of erection hardness in patients with ED; a
      dose-response relation was observed in the proportions of men with ED who graded
      their erections hard (rigid) enough for sexual penetration or completely hard and
      fully rigid.

PMID- 17011373
TI  - Erectile function and assessments of erection hardness correlate positively with
      measures of emotional well-being, sexual satisfaction, and treatment satisfaction
      in men with erectile dysfunction treated with sildenafil citrate (Viagra).
AB  - We aimed to determine whether erectile function (EF) and assessments of erection
      hardness correlate positively with measures of psychosocial outcomes (ie,
      emotional well-being, sexual satisfaction, and satisfaction with erectile
      dysfunction [ED] treatment) in men treated with sildenafil citrate (Viagra;
      Pfizer Inc, New York, NY). Data were collected from 33 worldwide phase 2, 3, and
      4 sildenafil clinical trials, which included almost 10,000 men with ED. Most of
      these trials were randomized, double-blind, and placebo-controlled (n = 27) and
      were undertaken to assess doses of 50 mg adjustable to 25 mg or 100 mg, depending
      on efficacy and tolerability (n = 32). Doses were taken approximately 1 hour
      before anticipated sexual activity but not more often than once daily. EF was
      assessed with use of the EF domain of the International Index of Erectile
      Function (IIEF) and with assessments of erection hardness (Erection Hardness
      Grading Scale [EHGS] and IIEF Q2 [the frequency of erections hard enough for
      penetration]). Change (baseline to end point) in emotional well-being in men
      treated for ED was assessed with the Self-Esteem and Relationship (SEAR)
      questionnaire, which consisted of the Confidence domain (ie, the Self-Esteem
      subscale and Overall Relationship subscale) and the Sexual Relationship domain.
      End point treatment satisfaction (overall, speed of onset, and duration of
      action) was assessed with the Erectile Dysfunction Inventory of Treatment
      Satisfaction (EDITS). The IIEF was used to assess change and end point sexual
      satisfaction by means of the Intercourse Satisfaction domain, Q7 (frequency of
      satisfactory sexual intercourse), and the Overall Satisfaction domain (ie, Q13,
      satisfaction with sex life, and Q14, satisfaction with sexual relationship). In
      men treated with sildenafil for ED, scores for measures of EF (IIEF EF domain,
      IIEF Q2) and the percentage of erections graded completely hard and fully rigid
      (EHGS grade 4) correlated positively with scores for measures of psychosocial
      outcomes (SEAR emotional well-being, IIEF sexual satisfaction, and EDITS ED
      treatment satisfaction), indicating that when EF improved and erection hardness
      increased, these measures of psychosocial function also improved.

PMID- 17011374
TI  - A prospective study of the beneficial effects of dose optimization and customized
      instructions on patient satisfaction with sildenafil citrate (Viagra) for
      erectile dysfunction.
AB  - Our objective was to assess the effects of customized instructions and dose
      optimization on treatment satisfaction and improvement in erectile function (EF)
      with sildenafil citrate in men with erectile dysfunction (ED) who had not been
      previously treated with a phosphodiesterase-5 inhibitor. This 8-week,
      multicenter, open-label, flexible-dose (25, 50, or 100 mg sildenafil) study
      included 2 phases. During phase 1, patients took 50 mg sildenafil and followed
      the sildenafil sample package instructions. In phase 2, sildenafil dose could be
      adjusted on the basis of efficacy and tolerability, and investigators provided
      additional customized instructions. The primary efficacy variable was the
      satisfaction rate (defined as patients responding "very" or "somewhat" satisfied
      to the Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS] Question
      1). Other efficacy assessments included the International Index of Erectile
      Function (IIEF) and the percentage of successful sexual intercourse attempts. Of
      1109 men (mean age, 54+/-13 years) treated, 867 completed the study. In phase 1,
      75% of patients were very or somewhat satisfied with treatment. Mean EF domain
      score on the IIEF increased from 14.3 at baseline to 23.5, and 79% of sexual
      intercourse attempts were successful. In phase 2, 53% of patients increased their
      sildenafil dose to 100 mg and 2% decreased to 25 mg. Satisfaction with sildenafil
      increased to 86%, 91% of sexual intercourse attempts were successful, and mean
      IIEF EF domain score increased to 25.7. Of the 196 men who were not initially
      satisfied at the end of phase 1, 64% became very or somewhat satisfied with
      treatment by the end of phase 2. Initially high levels of efficacy and
      satisfaction with sildenafil were achieved when patients were provided with only
      the sample package instructions and the recommended 50-mg starting dose. These
      results were enhanced with dose optimization, individual patient counseling, and
      customized instructions.

PMID- 17011375
TI  - Cardiovascular safety of sildenafil citrate (Viagra): an updated perspective.
AB  - Sildenafil citrate (Viagra; Pfizer Inc, New York, NY) relaxes vascular smooth
      muscle, resulting in modest reductions in blood pressure that are insufficient to
      stimulate a reflex increase in heart rate. These blood pressure reductions are
      similar for healthy men and men with coronary artery disease (CAD) or who use
      antihypertensive drugs. Sildenafil does not affect the force of cardiac
      contraction, and cardiac performance is unaffected. Sildenafil is mildly
      vasodilating in the coronary circulation and does not increase the risk of
      ventricular arrhythmia. During exercise and recovery, sildenafil does not cause
      clinically significant alterations in hemodynamic parameters in men with CAD, and
      it has no negative effects on coronary oxygen consumption, ischemia, or exercise
      capacity. Clinical trial data from >13,000 patients, 7 years of international
      postmarketing data, and observational studies of >28,000 men in the United
      Kingdom and 3813 men in the European Union reveal that (1) there are no special
      cardiovascular concerns when sildenafil is used in accordance with product
      labeling and (2) the risk for serious events such as myocardial infarction or
      death is not increased. However, because safety has not been established in
      patients with recent serious cardiovascular events, hypotension or uncontrolled
      hypertension, or retinitis pigmentosa, physicians should consult their current
      local prescribing information before prescribing sildenafil for these patients.
      Among men with erectile dysfunction treated with sildenafil, the adverse event
      profile is similar overall to that in men with comorbid cardiovascular disease
      (CVD), it is similar between those with and without CAD, and it is similar
      between those who take and those who do not take antihypertensive drugs
      (regardless of the number or class). In a controlled interaction study of
      sildenafil and amlodipine, the mean additional reduction in supine blood pressure
      was 8 mm Hg systolic and 7 mm Hg diastolic. Sildenafil should be used with
      caution in patients who take alpha-blockers because coadministration may lead to
      symptomatic hypotension in some individuals. When sildenafil is coadministered
      with an alpha-blocker, patients should be stable on alpha-blocker therapy before
      initiating sildenafil treatment and sildenafil should be initiated at the lowest
      dose. Also, in the absence of information specific to mixed alpha/beta blockers,
      such as carvedilol and labetalol, similar care should be taken as for alpha
      blockers. Sildenafil potentiates the hypotensive effects of nitrates, and its
      administration to patients who are using organic nitrates in any form, either
      regularly or intermittently, is contraindicated. Before prescribing sildenafil,
      physicians should carefully consider whether their patients with underlying CVD
      could be affected adversely by resuming sexual activity. Management
      recommendations based on cardiovascular risk, from the Second Princeton Consensus
      Conference, are presented.

PMID- 17011378
TI  - The overactive bladder: Epidemiology and morbidity.
AB  - The International Continence Society recognizes the overactive bladder (OAB) as a
      "symptom syndrome suggestive of lower urinary tract dysfunction" that is defined
      as "urgency, with or without urge incontinence, usually with frequency and
      nocturia." Patients who have OAB are often sleep deprived and their sexual life
      is hindered. These patients have a restricted social life and an increased risk
      for depression. Accurate prevalence figures are difficult to obtain because most
      patients consider OAB an inevitable part of aging and some patients are too
      embarrassed to seek diagnosis. Primary care physicians need to be educated about
      the importance of identifying this clinical problem and managing it in a way that
      will minimize morbidity and maximize quality-of-life improvement. This article
      describes the various aspects of OAB, with special emphasis on epidemiology and
      morbidity.

PMID- 17011379
TI  - Oxybutynin in detrusor overactivity.
AB  - Oxybutynin has been used for the management of detrusor overactivity for over 30
      years and has withstood medical scrutiny and the test of time throughout the
      world. Although several agents in the class of bladder relaxants have only
      recently been studied, oxybutynin's effectiveness in reducing urinary frequency
      and urge urinary incontinence is unquestioned in the medical literature.
      Oxybutynin is extremely safe and effective in almost every population including
      children, the elderly, and those who have neurogenic bladder. With more
      preparations available and more dosing flexibility than any other anticholinergic
      medication on the market, oxybutynin remains the "gold standard" for first-line
      therapy for patients who have detrusor overactivity.

PMID- 17011380
TI  - Tolterodine for treatment of overactive bladder.
AB  - Tolterodine was developed as an antimuscarinic agent specifically for the
      treatment of overactive bladder. Initial in vivo studies demonstrated a
      functional selectivity for the muscarinic receptors in the urinary bladder over
      the salivary glands, and subsequent clinical trials showed an overall superior
      tolerability profile compared with other drugs in the same class (ie,
      oxybutynin). With immediate- and extended-release formulations and sustained
      clinical efficacy during long-term treatment, tolterodine gas become an important
      treatment option for the symptoms of overactive bladder.

PMID- 17011381
TI  - Transdermal oxybutynin for overactive bladder.
AB  - Overactive bladder is commonly treated with oral anticholinergic drugs such as
      oxybutynin chloride. Although oral anticholinergic agents have been effective in
      controlling urinary urgency and frequency and in decreasing incontinence
      episodes, adverse events, particularly dry mouth, often cause patients to
      discontinue oral therapy and to endure incontinence. Oxybutynin can be delivered
      transcutaneously, maintaining the efficacy of oral oxybutynin while significantly
      minimizing the side effects (eg, dry mouth) that may complicate therapy. By
      avoiding hepatic and gastrointestinal metabolism of oxybutynin, less N
      desethyloxybutynin is produced (this compound is deemed responsible for the
      anticholinergic side effects such as dry mouth). This novel oxybutynin
      formulation offers patients who have overactive bladder and urge urinary
      incontinence a well-tolerated option for managing the symptoms of overactive
      bladder.

PMID- 17011382
TI  - Trospium chloride: Distinct among other anticholinergic agents available for the
      treatment of overactive bladder.
AB  - Trospium chloride is an antimuscarinic agent indicated for the treatment of
      overactive bladder with symptoms of urge urinary incontinence, urgency, and
      urinary frequency. It has been available in Europe for over 20 years and in the
      United States since May 2004. Trospium has pharmacologic properties that are
      distinct from other antimuscarinic agents. The safety and efficacy profiles of
      trospium and how its pharmacologic properties contribute to these profiles form
      the basis for this review. The low incidence of adverse event of central nervous
      system effects and the efficacy parameters of "urgency" and "onset of action" are
      highlighted.

PMID- 17011383
TI  - Darifenacin: Pharmacology and clinical usage.
AB  - Darifenacin is one of several recently approved antimuscarinics for the treatment
      of overactive bladder (OAB) and urge urinary incontinence. Darifenacin is an
      effective drug for the treatment of OAB and is tolerated by patients.
      Darifenacin's M3 selectivity is unique among antimuscarinics. This M3 selectivity
      could confer advantages in patients who have cardiovascular side effects
      (tachycardia), impaired cognition, complaints of dizziness, or sleep
      disturbances. In some studies, darifenacin caused less dry mouth than oxybutynin.
      Rates of constipation, although significant, are tolerated and rarely a cause for
      discontinuation in clinical trials. This review describes the role of M3
      receptors and covers the mechanism of action, pharmacokinetic properties,
      clinical efficacy safety and tolerability, drug interactions, and dosing
      guidelines for darifenacin.

PMID- 17011384
TI  - Solifenacin.
AB  - Pharacologic therapy has been the mainstay of treatment for patients who have
      overactive bladder. In recent years, a number of new antimuscarinic agents have
      been introduced. Solifenacin succinate is a new once-daily antimuscarinic agent
      that is an effective and well-tolerated treatment option for patients who have
      overactive bladder. Solifenacin increases functional bladder capacity and
      decreases urgency, frequency, and incontinence. In pharmacokinetic studies,
      solifenacin demonstrated selectivity for the bladder over the salivary gland;
      thus, it is likely that the bladder selectivity of this agent is responsible for
      the low incidence of dry mouth and constipation reported in the clinical trials.

PMID- 17011385
TI  - Sacral nerve stimulation for the overactive bladder.
AB  - Pharmacotherapy is the first-line treatment for overactive bladder, but many
      patients discontinue drug therapy because of intolerable side effects, expense,
      or lack of longterm adherence. Alternative treatments are needed for patients who
      are unable to tolerate pharmacotherapy or who do not derive the desired benefits.
      Sacral nerve stimulation therapy has evolved into one of the most widely accepted
      treatment modalities in the arena of neurourology. Sacral nerve stimulation
      activates or "resets" the somatic afferent inputs that play a pivotal role in the
      modulation of sensory processing for micturition reflex pathways in the spinal
      cord. This minimally invasive technology offers a safe, reliable, and durable
      treatment for lower urinary tract dysfunction.

PMID- 17011386
TI  - The case for bladder botulinum toxin application.
AB  - Botulinum toxin (BoNT) has been shown to be and effective agent in suppressing
      detrusor overactivity due to neurogenic causes. Recently, BoNT has been extended
      to patients who have idiopathic detrusor overactivity. This article reviews the
      use of BoNT to treat disorders of neurogenic detrusor overactivity and
      establishes BoNT as a therapeutic modality to treat idiopathic bladder
      overactivity. It is important to remember that the application of BoNT in the
      lower urinary tract is not approved by the regulatory agencies and caution should
      be applied until larger randomized clinical studies are completed.

PMID- 17011387
TI  - Local effects of antimuscarinics.
AB  - Overactive bladder (OAB) syndrome has been estimated to occur in nearly 17% of
      the population. The most common drug treatments for OAB are antimuscarinic agents
      that act to increase bladder capacity and decrease the urge to urinate during the
      storage phase. An increasing number of studies have focused on te role and
      mechanism of muscarinic acetylcholine receptors for the regulation of afferent
      activity during urine storage. Interactions between muscarinic receptors in the
      urothelium, afferent nerves, or myofibroblasts and locally released acetylcholine
      might be involved in the emergence of detrusor overactivity and OAB. Therefore,
      antimuscarinic agents may be effective in treating OAB not only by suppression of
      muscarinic receptor-mediated detrusor muscle contractions but also by modulation
      of muscarinic receptor-bladder afferent interactions.

PMID- 17011388
TI  - Local drug delivery to bladder using technology innovations.
AB  - Local delivery of drugs directly into the bladder by way of a urethral catheter
      is a clever approach to optimize drug delivery to the disease site while reducing
      systemic bioavailability. Pharmacotherapy by this route is referred to as
      intravesical delivery. In recent years, intravesical delivery has been used in
      combination with and oral regimen of drugs or as second-line treatment for
      neurogenic bladder and detrusor overactivity. Negligible absorption of instilled
      drugs into the systemic circulation explains the near-minimal adverse toxicity
      reported with this form of therapy. The authors discuss shortcomings of the
      current options available for intravesical delivery and provide a broad overview
      of the latest advances through technology innovation to overcome these drawbacks.

PMID- 17011389
TI  - When to use antimuscarinics in men who have lower urinary tract symptoms.
AB  - Although alpha-blockers are commonly used and generally effective in men who have
      symptomatic bladder outlet obstruction (BOO), a subset of these patients who have
      detrusor overactivity (DOA) often complain of persistent symptoms even after
      alpha-blocker therapy. What are the barriers to using antimuscarinics induce
      additional benefit? Should these men be treated primarily with antimuscarinics?
      The authors review several recent publications that look at this important issue
      and discuss when antimuscarinics should be used. It appears that BOO with
      concomitant DOA can be safely and accurately treated with a combination of alpha
      blockers and antimuscarinics.

PMID- 17011390
TI  - The promise of beta3-adrenoceptor agonists to treat the overactive bladder.
AB  - The detrusor muscle contains beta-adrenoceptors (beta-ARs), of which two subtypes
      -beta1-AR and beta2-AR--have been identified in most species. Although beta2-AR
      has an important role in muscle relaxation, evidence suggests that a third
      subtype--beta3-AR--mediates relaxation of human detrusor muscle. This article
      reviews the evidence for beta3-AR in human detrusor muscle and urothelium and
      discusses the potential use of beta3-AR agonists for the treatment of overactive
      bladder. In addition, the cAMP-dependent and -independent mechanisms of
      relaxation by way of beta-ARs in rat detrusor muscle, with and without pre
      contraction, are reported. Finally, the consequences of mutation of a beta3-AR
      gene (relating to the pathophysiology of idiopathic detrusor instability) are
      discussed.

PMID- 17011392
TI  - Cesarean delivery: background, trends, and epidemiology.
AB  - OBJECTIVE: To examine trends in cesarean delivery for the overall population and
      for women with "no indicated risk" for cesarean section, and to summarize the
      available literature on "maternal request" cesarean deliveries. FINDINGS: Nearly
      3 in 10 births were delivered by cesarean section in 2004 (29.1%), the highest
      rate ever reported in the United States. The overall rate has increased by over
      40% since 1996, reflecting two concurrent trends: an increase in the primary rate
      (14.6% to 20.6%), and a steep decline in the rate of vaginal birth after cesarean
      (28.3% to 9.2%). There has been a clear increase in primary cesarean delivery
      without a medical or obstetrical indication, and studies using hospital discharge
      data or birth certificate data estimate the rate of primary cesarean deliveries
      with no reported medical or obstetrical indication to be between 3% and 7% of all
      deliveries to women who had not had a previous cesarean delivery. However, these
      studies contain no direct information on whether these cesareans were the result
      of maternal request or because of physician recommendation. There was little data
      to support the contention that the rise in the cesarean rate was the result of
      maternal request. CONCLUSION: There are no systematic data available on cesarean
      delivery by "maternal request." However, the rate of primary cesarean delivery is
      increasing rapidly for women of all ages, races, and medical conditions, as well
      as for births at all gestational ages. Since a first cesarean section virtually
      guarantees that subsequent pregnancies will be cesarean deliveries (the repeat
      cesarean delivery rate is now almost 91%), research is needed on physician
      practice patterns, maternal attitudes, clinical outcomes for mother and infant
      (harms, benefits), and clinical and nonclinical factors (institutional, legal,
      economic) that affect the decision to have a cesarean delivery.

PMID- 17011393
TI  - Maternal mortality with cesarean delivery: a literature review.
AB  - OBJECTIVE: We sought to determine the present-day risk of maternal death with
      cesarean delivery. METHODS: We reviewed the recent literature (years in analysis:
      1975-2001) identified in a literature search and included data from the Royal
      College of Obstetricians and Gynaecologists. FINDINGS: There were no publications
      with an ideal trial design and adequate power to establish the relationship
      between maternal mortality and method of delivery. Three studies, including the
      one randomized control trial included in analysis, and the Royal College of
      Obstetricians and Gynaecologists data suggest no significant difference in
      maternal mortality with cesarean delivery as compared with vaginal delivery.
      CONCLUSIONS: The strongest publications suggest there may not be an increased
      risk of maternal death with cesarean delivery as compared with vaginal delivery;
      however, there are inadequate data to accurately demonstrate the present-day risk
      of maternal death with cesarean delivery.

PMID- 17011394
TI  - Maternal request cesarean versus planned spontaneous vaginal delivery: maternal
      morbidity and short term outcomes.
AB  - Since no randomized trial evaluates maternal morbidity from planned cesarean
      versus planned vaginal delivery, the issue must be addressed indirectly from
      retrospective cohort studies of vertex fetuses by actual or planned delivery
      route, and retrospective or randomized studies of breech fetuses by planned
      delivery route. The available data, although limited, suggest that term planned
      cesarean and planned vaginal delivery have similarly low rates of absolute and
      relative short-term maternal morbidity. Endometritis and cystitis are more
      frequent with cesarean, whereas hemorrhage is more frequent with planned vaginal
      delivery. Much of the morbidity of planned vaginal delivery is the morbidity of
      unplanned cesarean in labor and operative vaginal delivery, particularly forceps.
      Thus, the relative risk of short-term maternal morbidity of planned cesarean
      versus planned vaginal delivery will depend on the proportion of women in each
      group ultimately delivering in the planned manner and the frequency with which
      delivery occurs by an alternative unplanned method.

PMID- 17011395
TI  - Sexual function and childbirth.
AB  - OBJECTIVE: This manuscript reviews the potential impact of cesarean delivery on
      maternal sexual function. FINDING: The majority of new mothers resume intercourse
      within the first 3 months after delivery. However, during the first year after
      delivery, the majority of women experience at least one problem related to sexual
      function. The question with respect to maternal-choice cesarean is whether this
      obstetrical intervention affects maternal sexual function. We review the
      available evidence regarding sexual function after cesarean delivery and present
      several plausible mechanisms by which route of delivery could impact long-term
      postpartum sexual function. CONCLUSION: Further research is needed to investigate
      whether maternal-choice cesarean delivery affects female sexual function.

PMID- 17011397
TI  - Anal incontinence: relationship to pregnancy, vaginal delivery, and cesarean
      section.
AB  - OBJECTIVE: To review the current literature concerning anal incontinence (AI),
      pregnancy, and route of delivery. FINDING: AI is the involuntary loss of flatus,
      liquid, or solid stool that is a social or hygienic problem. AI has been reported
      in 5% to 26% of women during the first year following vaginal delivery. AI is
      strongly associated with occult and overt sphincter lacerations and operative
      vaginal delivery. The role of pregnancy itself and the impact of cesarean
      delivery on AI are unclear. Elective cesarean section has not been shown to
      decrease the risk of AI. CONCLUSION: The majority of current studies lack the
      power, matched controls, and long-term follow up to make recommendations
      concerning the mode of delivery and prevention of AI. The natural history of AI
      and development of symptoms as women age also remains unclear.

PMID- 17011396
TI  - Cesarean delivery on request: reproductive consequences.
AB  - OBJECTIVE: The objective of this review is to examine the long term reproductive
      health consequences of cesarean delivery on maternal request. FINDINGS: In the
      first delivery, cesarean delivery appears to hold small risk of reproductive
      complications compared to vaginal delivery. Primary cesarean delivery can affect
      subsequent pregnancies. The most serious reproductive health consequences of
      prior cesarean delivery occur in subsequent pregnancies. These complications
      include: unexplained fetal death apparent from 34 weeks gestation onward;
      abnormalities of placentation which increase with a greater number of cesarean
      deliveries; risk of uterine rupture and uterine scar dehiscence. CONCLUSIONS:
      Primary cesarean delivery carries risk for subsequent pregnancies. While the
      studies reviewed do not specifically refer to cesarean delivery on request, it is
      likely that the results would be similar. Overall, in considering the specific
      question of long term reproductive health, the risks of maternal request cesarean
      delivery outweigh the benefits.

PMID- 17011398
TI  - Urinary incontinence: is cesarean delivery protective?
AB  - About half of all women develop transient urinary incontinence during pregnancy.
      Three months postpartum, the prevalence and incidence rates of urinary
      incontinence are 9% to 31% and 7% to 15%, respectively. Antenatal incontinence
      increases the risk of postpartum incontinence, which in turn increases the risk
      of long-term persistent incontinence. After the first delivery, women delivered
      vaginally have two-fold more incontinence than those delivered by cesarean. The
      protective effect of cesarean on urinary incontinence may dissipate after further
      deliveries, decreases with age, and is not present in older women. Data are mixed
      about whether cesarean done before labor confers greater protection than cesarean
      done after labor. To understand the true impact of cesarean delivery on urinary
      incontinence, future studies must compare incontinence by planned (not actual)
      delivery modes, consider a woman's entire reproductive career, focus on leakage
      severe enough to be problematic, consider other bladder symptoms as well as
      incontinence, and take into account other risk factors, particularly antepartum
      urinary incontinence.

PMID- 17011399
TI  - Cesarean delivery on maternal request versus planned vaginal delivery: impact on
      development of pelvic organ prolapse.
AB  - Pelvic floor disorders (PFDs) (ie, pelvic organ prolapse, urinary and fecal
      incontinence) are prevalent and impact quality of life as well as our health care
      system. It has been estimated that the demand for health care related to PFDs
      will increase at twice the rate of the population itself. This speaks to the fact
      that PFDs are an important women's and public health issue, warranting studies
      aimed at their prevention.

PMID- 17011400
TI  - Cesarean section on request at 39 weeks: impact on shoulder dystocia, fetal
      trauma, neonatal encephalopathy, and intrauterine fetal demise.
AB  - PURPOSE: The purpose of this analysis was to determine the impact on specific
      forms of neonatal morbidity and mortality by allowing women to opt for delivery
      by elective cesarean section at 39 weeks of gestation (EGA). According to the
      National Vital Statistics Reports, over 70% of deliveries in the U.S. annually
      are at gestational ages>or=39 weeks EGA. Estimating that over 4 million
      deliveries occur annually in the United States, this would yield approximately 3
      million pregnancies wherein the woman may exercise her choice for either primary
      or repeat cesarean section at 39 weeks EGA or at the point when labor is
      established. METHODS: A search was conducted using Ovid Medline spanning the past
      10 years using the following key words: fetal trauma, shoulder dystocia, brachial
      plexus palsy, neonatal skull fracture, obstetrical trauma, traumatic delivery,
      intrauterine fetal demise, stillbirth, fetal demise, and neonatal encephalopathy.
      Using this search technique, over 2100 articles were identified. The abstracts
      were reviewed and pertinent articles were chosen for further consideration. The
      identified articles and their applicable references were obtained for inclusion
      in this review. Preference was given to publications on or after the year 2000
      with the exception of classical or sentinel articles, which were included without
      regard to year of publication. RESULTS: Four major categories of neonatal
      morbidity and mortality are discussed: Shoulder dystocia: Accepting that we do
      not have a successful method for the prediction or prevention of shoulder
      dystocia, the question becomes, "What is the chance that a baby will sustain a
      permanent brachial plexus injury at delivery?" Additionally, is there a
      significant protective effect of cesarean section in reducing the risk of such
      injury? Currently, the occurrence rate of brachial plexus palsy at the time of
      vaginal delivery ranges from 0.047% to 0.6% and for cesarean section from 0.0042%
      to 0.095%. Using a composite estimate of the risk of 0.15% for vaginal deliveries
      and applying it to the 3 million deliveries>or=39 weeks EGA, approximately 4500
      cases of brachial plexus palsy would occur. If only 15% of these injuries were
      permanent, 675 permanent brachial plexus palsies would occur annually. If the
      risk of permanent injury is 1 in 10,000 as reported by Chauhan, 300 permanent
      brachial plexus palsies would occur annually in the United States. The range then
      for permanent brachial plexus injury that could be avoided with cesarean section
      on request would appear to vary between 1 in 5000 and 1 in 10,000 vaginal births.
      Fetal trauma: The incidence of significant birth trauma varies from 0.2 to 1 to 2
      per 1000 births. The use of sequential instruments, for example, vacuum followed
      by forceps or vice versa, is specifically associated with an unacceptably high
      injury rate. Intrapartum-related neonatal deaths of vertex singleton fetuses with
      birthweights>2500 g from traumatic cranial or cervical spine injury secondary to
      vacuum- or forceps-assisted vaginal delivery are still occurring. Overall, the
      frequency of significant fetal injury is significantly greater with vaginal
      delivery, especially operative vaginal delivery, than with cesarean section for
      the nonlaboring woman at 39 weeks EGA or near term when early labor has been
      established. Neonatal encephalopathy: The prevalence of moderate to severe
      neonatal encephalopathy is 3.8/1000 term live births with a neonatal fatality
      rate of 9.1%. In 4% to 10% of cases, the etiology appears to be pure intrapartum
      hypoxia. Intrapartum hypoxia superimposed on antepartum risk factors may account
      for up to 25% of the moderate to severe encephalopathies, according to one
      cohort. A paradox in the data thus far is that infants born to nonlaboring women
      delivered by cesarean section had an 83% reduction in the occurrence of moderate
      or severe encephalopathy. Considering a prevalence of moderate or severe neonatal
      encephalopathy of 0.38% and applying it to the 3 million deliveries occurring at
      >or=39 weeks EGA in the United States annually, 11,400 cases of moderate to
      severe encephalopathy would occur. The rate of encephalopathy observed in infants
      delivered by cesarean section would yield approximately 1938 cases. This net
      difference in moderate to severe encephalopathy would represent 9462 cases
      annually in the United States that could be prevented with elective cesarean
      section. Although cesarean delivery may be protective for the development of
      neonatal encephalopathy, to date it has not proven to be protective of long-term
      neurologic injury in the form of cerebral palsy with or without mental
      retardation and/or seizure disorders. Intrauterine fetal demise: Copper reported
      that the rate of stillbirth is consistent from 23 to 40 weeks EGA with about 5%
      of all stillbirths occurring at each week of gestation. Yudkin reported a rate of
      0.6 stillbirths per 1000 live births from 33 to 39 weeks EGA. After 39 weeks EGA,
      a significant increase in the stillbirth rate was reported (1.9 per 1000 live
      births). Fretts reported on fetal deaths per 1000 live births from 37 to 41 weeks
      of gestational age, showing that the rate progressively increased from 1.3 to 4.6
      with each week of gestation. It can be estimated that delivery at 39 weeks EGA
      would prevent 2 fetal deaths per 1000 living fetuses. This would translate into
      the prevention of as many as 6000 intrauterine fetal demises in the United States
      annually-an impact that far exceeds any other strategy implemented for stillbirth
      reduction thus far. CONCLUSION: It is reasonable to inform the pregnant woman of
      the risk of each of the above categories, in addition to counseling her regarding
      the potential risks of a cesarean section for the current and any subsequent
      pregnancies. The clinician's role should be to provide the best evidence-based
      counseling possible to the pregnant woman and to respect her autonomy and
      decision-making capabilities when considering route of delivery.

PMID- 17011401
TI  - Neonatal mortality and morbidity after elective cesarean delivery versus routine
      expectant management: a decision analysis.
AB  - A number of competing risks and benefits influence the rates of neonatal
      morbidity and mortality in elective cesarean delivery versus expectant
      management. To compare these rates, we developed complex decision trees to model
      the expected outcomes among hypothetical cohorts of 1,000,000 uncomplicated
      pregnancies undergoing elective cesarean delivery versus 1,000,000 comparable
      pregnancies undergoing routine pregnancy management. A separate tree was created
      for each complication, including neonatal death, respiratory morbidity,
      intracranial hemorrhage, and brachial plexus injury. We found that neonatal
      mortality was increased among elective cesarean deliveries, but perinatal
      mortality was higher with routine expectant management due to fetal deaths.
      Respiratory morbidity was substantially more common among infants delivered by
      elective cesarean delivery, whereas intracranial hemorrhage and brachial plexus
      injury were less common. We conclude that the fetal/neonatal impact of elective
      cesarean is mixed, but any improvement in perinatal health is likely to be small.

PMID- 17011402
TI  - Respiratory transition in infants delivered by cesarean section.
AB  - One of the biggest challenges a newborn faces after birth is the task of making a
      smooth transition to air breathing. This task is complicated by the fact that
      fetal lungs are full of fluid which must be cleared rapidly to allow for gas
      exchange. Respiratory morbidity as a result of failure to clear fetal lung fluid
      is not uncommon, and can be particularly problematic in some infants delivered by
      elective cesarean delivery (ECS). Given the high rates of cesarean deliveries in
      the USA and worldwide, the public health and economic impact of morbidity in this
      subgroup is considerable. Whereas the occurrence of birth asphyxia, trauma, and
      meconium aspiration is reduced by elective Cesarean delivery, the risk of
      respiratory distress secondary to transient tachypnea of the newborn, surfactant
      deficiency, and pulmonary hypertension is increased. It is clear that physiologic
      events in the last few weeks of pregnancy coupled with the onset of spontaneous
      labor are accompanied by changes in the hormonal milieu of the fetus and its
      mother, resulting in preparation of the fetus for neonatal transition. Rapid
      clearance of fetal lung fluid is a key part of these changes, and is mediated in
      large part by transepithelial Na reabsorption through amiloride-sensitive Na
      channels in the alveolar epithelial cells, with only a limited contribution from
      mechanical factors and Starling forces. This chapter discusses the physiologic
      mechanisms underlying fetal lung fluid absorption and explores potential
      strategies for facilitating neonatal transition when infants are delivered by ECS
      before the onset of spontaneous labor.

PMID- 17011403
TI  - Cesarean delivery on maternal request: wise use of finite resources? A view from
      the trenches.
AB  - Cesarean section rates are rising in the United States and were at an all time
      high of 29 percent in 2004. Within this context, the issue of cesarean section on
      maternal request has been described as being part of a "perfect storm" of
      medical, legal and personal choice issues, and the lack of an opposing view. An
      increasing cesarean section rate adds an economic burden on already highly
      stressed medical systems. There is an incremental cost of cesarean section
      compared to vaginal delivery. The issue of cost must also be considered more
      broadly. Rising cesarean section rates are associated with a longer length of
      stay and a higher occupancy rate. This high occupancy rate leads to the diversion
      of critical care obstetric transports and has dramatically reduced patient
      satisfaction. These diversions, and the resultant inability to provide needed
      care to pregnant women, represent a profound societal cost. These critical care
      diversions and reduced patient satisfaction also negatively impact a health care
      institution's financial bottom line and competitiveness. The impact of a rising
      cesarean section rate on both short and long-term maternal and neonatal
      complications, and their associated costs, must also be taken into account. The
      incidence of placenta accreta is increasing in conjunction with the rising
      cesarean section rate. The added costs associated with this complication (MRI,
      Interventional Radiology, transfusion, hysterectomy, and intensive care
      admission) can be prohibitive. It has also been demonstrated that infants born by
      scheduled cesarean delivery are more likely to require advanced nursery support
      (with all its associated expense) than infants born to mothers attempting vaginal
      delivery. The practice of maternal request cesarean section, with limited good
      data and obvious inherent risk and expense, is increasing in the USA. Patient
      autonomy and a woman's right to choose her mode of delivery should be respected.
      However, in our opinion, based on the current evidence regarding cesarean
      delivery on maternal request, promotion of primary cesarean section on request as
      a standard of care or as a mandated part of patient counseling for delivery will
      result in a highly questionable use of finite resources. As of 2004, 46 million
      Americans did not even have basic health insurance. It is critical that we not
      allow ourselves to be dragged into the eye of a "perfect storm." This conference
      is an important step in the rational and objective analysis of this issue.

PMID- 17011404
TI  - The ethics of cesarean section by choice.
AB  - In responding to patient requests for cesarean section, physicians must consider
      ethical principles. Obstetricians have autonomy and beneficence-based obligations
      to the mother, and the mother and the obstetrician have beneficence-based
      obligations to the fetus. Maternal autonomy is usually accepted as the most
      compelling ethical canon. However, the physician has a right to refuse requests.
      Thus, when a patient requests surgery, the physician may attempt to dissuade her
      and failing that either acquiesce or, feeling that professional conscience would
      not allow him/her to honor that request, refuse. Which choice is made should
      reflect the provider's believe about the strength of the supporting data. Given
      the need to recognize patient autonomy, to respect patient values even as one
      tries to motivate patients to work toward the highest health values, and to
      acknowledge women's primacy as fetal champions, a physician should be loathe to
      refuse unless the data regarding cesarean section by choice are wholly tilted
      away from maternal-child interests. If the data are in the realm of equipoise,
      even if not at the tipping point, discussing options, attempting to dissuade
      patients but ultimately acquiescing to their judgment would not be incompatible
      with obstetrical ethics.

PMID- 17011407
TI  - Herbal medicines for the treatment of rhinosinusitis: a systematic review.
AB  - OBJECTIVES: To assess the efficacy of herbal medicines for treating
      rhinosinusitis. DATA SOURCE: Five electronic databases, bibliographies of located
      papers, manufacturers, and experts in the field. REVIEW METHODS: Inclusion of
      randomized clinical trials (RCT) testing any herbal medicine in rhinosinusitis,
      as sole or adjunctive treatment. Data were extracted independently by two
      reviewers following a predetermined protocol. RESULTS: Ten RCTs, testing six
      different herbal products against placebo (8 RCTs) or "no additional treatment"
      (2 RCTs) were included. Four RCTs tested Sinupret as adjunctive treatment for
      either acute (3 RCTs) or chronic (1 RCT) rhinosinusitis. The quality of these
      studies varied, but two in acute sinusitis, including the largest and best
      quality study, and one in chronic sinusitis reported significant positive
      findings. Three RCTs tested bromelain in either acute sinusitis (2 RCTs) or
      patients of mixed diagnosis (chronic and acute sinusitis), and all reported some
      positive findings. Metanalysis of the two RCTs in acute sinusitis suggested that
      adjunctive use of bromelain significantly improves some symptoms of acute
      rhinosinusitis. Single RCTs were identified for 4 other herbal products
      (Esberitox, Myrtol, Cineole, and Bi Yuan Shu) as treatments for sinusitis, all
      reported some positive results. The median methodological quality score was 3 of
      5. CONCLUSION: Evidence that any herbal medicines are beneficial in the treatment
      of rhinosinusitis is limited, particularly in chronic rhinosinusitis. There is
      encouraging evidence that Sinupret and bromelain may be effective adjunctive
      treatments in acute rhinosinusitis. Positive results from isolated RCTs of four
      other herbal products require independent replication.

PMID- 17011408
TI  - Grommets (ventilation tubes) for hearing loss associated with otitis media with
      effusion in children.

PMID- 17011409
TI  - Randomized double-blind study comparing 7- and 10-day regimens of faropenem
      medoxomil with a 10-day cefuroxime axetil regimen for treatment of acute
      bacterial sinusitis.
AB  - OBJECTIVE: To compare the efficacy and safety of faropenem medoxomil, 300 mg
      twice daily for seven or ten days, with cefuroxime axetil 250 mg twice daily for
      ten days in adults with acute bacterial sinusitis (ABS). STUDY DESIGN AND
      SETTING: Prospective, double-blinded, phase III trial with entry criteria
      consistent with FDA/IDSA guidelines for diagnosis of ABS. Primary efficacy
      parameter was clinical response at 7 to 21 days posttherapy. RESULTS: One
      thousand ninety-nine subjects were randomized and treated; 861 were efficacy
      valid. Clinical cure rates were 80.3% for seven days of faropenem, 81.8% for ten
      days of faropenem, and 74.5% for 10 days of cefuroxime axetil. The incidence of
      adverse events and premature discontinuations were similar for the three
      treatment regimens. CONCLUSIONS: Seven- and ten-day faropenem medoxomil regimens
      were similar (noninferior) to a ten-day cefuroxime axetil regimen based on
      clinical response in patients with ABS. SIGNIFICANCE: A seven-day course of
      faropenem medoxomil 300 mg twice-daily regimen is a promising alternative for
      treatment of ABS.

PMID- 17011410
TI  - Image-guided frontal trephination: a minimally invasive approach for hard-to
      reach frontal sinus disease.
AB  - OBJECTIVES: Peripherally located frontal sinus pathology may be unreachable with
      standard endoscopic techniques. Patients with superiorly or laterally based
      lesions often undergo osteoplastic flap with or without obliteration. Image
      guided frontal trephination (IGFT) can localize pathology and provide excellent
      exposure. We present 13 patients in whom this technique was applied. STUDY
      DESIGN: Medical records of 13 patients undergoing IGFT were retrospectively
      reviewed. RESULTS: The patients' mean age was 49.2 years, (range 14-79); follow
      up time was 29.9 months (range 12-39). Indications for IGFT were superiorly or
      laterally based mucoceles (3), fibrous dysplasia or osteoma (3), type 4 frontal
      cells (3), and frontal recess stenosis or ossification (4). In five patients,
      IGFT was combined with endoscopic transethmoid frontal sinusotomy; eight patients
      were treated through a trephination approach, and three patients underwent
      trephination with unilateral frontal sinus obliteration. One patient required
      revision; all others remain symptom free. CONCLUSIONS/SIGNIFICANCE: IGFT offers
      an attractive alternative to osteoplastic flap.

PMID- 17011411
TI  - Disease severity in acute bacterial rhinosinusitis is greater in patients
      infected with Streptococcus pneumoniae than in those infected with Haemophilus
      influenzae.
AB  - BACKGROUND: Streptococcus pneumoniae and Haemophilus influenzae are the most
      common causative pathogens in acute bacterial rhinosinusitis. A post hoc pooled
      analysis of four multinational Phase III clinical trials was conducted to compare
      disease severity in acute bacterial rhinosinusitis caused by S. pneumoniae or H.
      influenzae. METHODS: Patients were evaluated for acute bacterial rhinosinusitis
      clinician-assessed symptom severity and radiologic findings (total opacity,
      mucosal thickening, and air-fluid levels on maxillary sinus x-rays). Specimens
      for bacteriologic identification were collected by maxillary sinus tap, or by
      selective middle meatal cultures (sinus aspirates or swabs). RESULTS: Compared
      with patients infected with H. influenzae (n = 106), patients infected with S.
      pneumoniae (n = 143) showed a statistically significant higher incidence of
      severe disease (39.2% vs 23.6%, P = 0.0097) and total opacity (46.2% vs 29.2%, P
      = 0.0085). Mucosal thickening (47.6% vs 56.6%, P = 0.1616) and air-fluid levels
      (49% vs 56.6%, P = 0.2500) were comparable between the two groups. CONCLUSIONS:
      In acute bacterial rhinosinusitis, infection with S. pneumoniae is associated
      with more severe clinical symptoms and radiographic total opacification findings
      than infection with H. influenzae.

PMID- 17011412
TI  - Natural history of benign paroxysmal positional vertigo and efficacy of Epley and
      Lempert maneuvers.
AB  - We assessed the efficacy of Epley maneuver in patients with posterior canal
      benign paroxysmal positional vertigo (P-BPPV) and Lempert maneuver in patients
      with horizontal canal BPPV (H-BPPV). In patients with P-BPPV, positional vertigo
      in patients treated by Epley maneuver was significantly resolved more quickly
      than that in untreated patients. But in patients with H-BPPV, there were no
      significant differences of time course in remission of positional vertigo between
      untreated patients and patients treated by Lempert maneuver. Among the untreated
      patients, the positional vertigo in patients with H-BPPV was significantly
      resolved more quickly than that in patients with P-BPPV. Epley maneuver was
      effective for the treatment of patients with P-BPPV, whereas the efficacy of
      Lempert maneuver for the treatment of patients with H-BPPV was limited. The
      natural courses in remission of positional vertigo in untreated patients with H
      BPPV showed significantly faster resolution than that in patients with P-BPPV.

PMID- 17011413
TI  - Balance ability in patients with benign paroxysmal positional vertigo.
AB  - OBJECTIVE: The purpose of the study was to investigate the balance ability of the
      patients with benign paroxysmal positional vertigo (BPPV). STUDY DESIGN AND
      SETTING: Twenty-three patients (63.3 +/- 9.2 years of age) with a diagnosis of
      unilateral posterior semicircular canal BPPV were recruited. Static balance was
      measured in 4 conditions with eyes open and eyes closed: stance on firm surface,
      stance on foam surface, left leg stance, and right leg stance. Dynamic balance
      was measured in tandem walk test. Data of the patients with BPPV were compared to
      age-matched norm values of the healthy adults. RESULTS: The patients with BPPV
      demonstrated greater sway velocity in stance on foam surface with eyes closed (P
      < 0.05), in single leg stance with eyes closed (P < 0.001), and in tandem walk
      test (P < 0.05) compared to the healthy adults. CONCLUSIONS: Patients with BPPV
      demonstrated impaired static and dynamic balance ability particularly when
      depriving visual and changing proprioceptive inputs. SIGNIFICANCE: Clinically, in
      addition to canalith repositioning maneuver, balance retraining on different
      conditions may be a useful adjunct to treatment for patients with BPPV.

PMID- 17011414
TI  - Surgical treatment for vertigo: patient survey of vertigo, imbalance, and time
      course for recovery.
AB  - OBJECTIVES: To assess surgical treatment of vertigo by patient ratings of
      postoperative vertigo, imbalance, and timing of symptom improvement. METHODS: A
      total of 3637 surgeries for vertigo were performed since 1974. Questionnaires
      sent to a random sample of patients operated since 1994 were completed by 28
      endolymphatic sac shunt (ES), 54 vestibular nerve section (VNS), and 14
      labyrinthectomy patients. RESULTS: All groups rated current vertigo
      characteristics and AAO-HNS disability as improved (all P <or= 0.001), though
      "spinning dizziness" remained in some patients in each group. The ES and VNS
      groups rated all characteristics of imbalance as improved (all P <or= 0.001), but
      it remained present in the majority. Vertigo resolved within 2 months in 75%, but
      some indicated months or even 1 to 2 years before attacks stopped. CONCLUSIONS:
      Based on patient ratings, surgery improved vertigo in all surgical groups and
      improved imbalance for ES and VNS groups. Imbalance will likely remain after
      surgery for vertigo. Patients should be informed that symptoms may not
      immediately resolve.

PMID- 17011415
TI  - Palatal implants: a new approach for the treatment of obstructive sleep apnea.
AB  - OBJECTIVE: To evaluate the short-term safety and efficacy of palatal implants in
      patients with mild and moderate obstructive sleep apnea (OSA). STUDY DESIGN AND
      SETTING: A prospective, non-randomized study conducted at 5 clinical sites. Three
      polyester implants were placed in the soft palate under local anesthesia during a
      single-stage office procedure. Polysomnography was conducted at baseline and 90
      days post-procedure. Subjective quality of life data were collected. RESULTS:
      Fifty-three patients were evaluated; the apnea hypopnea index (AHI) decreased
      from 25.0 +/- 13.9 to 22.0 +/- 14.8 events/hour (P = 0.05). The Epworth
      Sleepiness Scale (ESS) decreased from 11.0 +/- 5.1 to 6.9 +/- 4.5 (P < 0.001),
      and the snore score decreased from 7.9 +/- 2.1 to 4.0 +/- 3.0 (P < 0.001). No
      serious complications occurred during the study. CONCLUSION: Palatal implants can
      be an effective initial low morbidity treatment option for patients diagnosed
      with mild to moderate OSA.

PMID- 17011416
TI  - Severity of obstructive sleep apnea: correlation with clinical examination and
      patient perception.
AB  - OBJECTIVE: To correlate clinical history, patient self-perception of obstructive
      sleep apnea, and physical examination with the severity of OSA. METHODS: One
      hundred and two consecutive patients were prospectively enrolled over a 6-month
      period. All patients underwent a comprehensive history and clinical examination,
      nasopharyngoscopy, and an overnight-attended polysomnogram. RESULTS: There were
      65 males and 37 females with a mean age of 50.2 +/- 11.3 years (range, 24 to 76
      years). The mean apnea-hypopnea index (AHI) was 37.9 +/- 27.7 (range, 0.7 to
      111.2). There was a strong correlation between patient self-perception of OSA
      severity and AHI (r = 0.499, P < 0.0001), and the correlation with AI was 0.577
      (P < 0.0001). OSA severity strongly correlated with Friedman Tongue Position
      grade, (r = 0.389, P < 0.0001), Friedman clinical staging, (r = 0.331, P =
      0.0007). Of significance, only 6.9% of patients with mild OSA had a >50% collapse
      of the base of tongue region, as compared to 65.9% of patients with severe OSA.
      CONCLUSION: There is good correlation between clinical examination parameters and
      the severity of OSA. An algorithm for surgical treatment of OSA should
      acknowledge both the site of obstruction and the severity of disease.

PMID- 17011417
TI  - Histologic effects of injection snoreplasty and radiofrequency in the rat soft
      palate.
AB  - OBJECTIVE: This study was undertaken to compare the effects of radiofrequency and
      injection snoreplasty on the histological structure of the soft palate in an
      animal model. STUDY DESIGN AND SETTING: This is a blinded, controlled histologic
      evaluation of rat soft palates that underwent separate palatal interventions.
      Fifty rats were divided into 5 groups of 10 rats (Group 1 = injection snoreplasty
      [IS], Group 2 = IS + steroid, Group 3 = saline injection, Group 4 =
      radiofrequency ablation [RFA], and Group 5 = no intervention). The animals were
      sacrificed after 24 hours, 1 week, 3 weeks, and 5 weeks. Then the soft palates
      were subjected to histological analysis. RESULTS: Histological analysis
      demonstrated normal remucosalization in all specimens, with fibrosis increased in
      Group 1. Interstitial edema was minimal in Group 2. Keratinization was most
      apparent in Group 4. CONCLUSION: Radiofrequency and injection snoreplasty stiffen
      the rat soft palate compared with controls.

PMID- 17011418
TI  - Quality of life outcomes in laryngeal and oropharyngeal cancer patients after
      chemoradiation.
AB  - OBJECTIVE: The purpose of this study was to compare quality of life issues in
      patients with advanced laryngeal versus oropharyngeal cancer after treatment with
      chemoradiation. DESIGN: A cohort study of 31 patients with laryngeal or
      oropharyngeal squamous cell carcinoma treated with chemoradiation completed the
      University of Washington quality of life instrument version 4 (UW-QOL v4).
      Statistical analysis was performed with Wilcoxon rank sum and chi-square tests.
      SETTING: Academic tertiary care center. RESULTS: Both groups reported similar
      impairment in the domains of swallowing, chewing, and taste. Oropharyngeal cancer
      patients reported significantly worse quality of life in the domain of saliva (P
      < 0.007). CONCLUSION: Swallowing, chewing, and taste were adversely affected by
      chemoradiation for both groups. Oropharyngeal patients experienced significantly
      worse problems with saliva than laryngeal patients. These patients reported high
      levels of satisfaction with health-related quality of life issues. SIGNIFICANCE:
      Specific head and neck subsites have different morbidities when treated with
      primary chemoradiation for advanced tumors.

PMID- 17011419
TI  - Laryngotracheal separation surgery: outcome in 60 patients.
AB  - OBJECTIVE: To determine the outcome of laryngotracheal separation (LTS) in 60
      patients in terms of the control and prevention of severe and persistent
      aspiration, morbidity and mortality, reversibility rate, and the influence of the
      presence of a tracheostomy. STUDY DESIGN: Retrospective study. RESULTS: LTS
      showed significant efficacy rates in terms of both treatment (87%) and prevention
      (100%) of pulmonary aspiration. Twenty-six (43%) patients developed postoperative
      complications. A tracheocutaneous fistula of the proximal tracheal stump was
      observed in 14 (23%) patients and was the most frequent complication, especially
      in patients with a therapeutic indication (P = 0.028) and in those with a
      tracheostomy (P = 0.058). Reversion of LTS was possible in 12 (20%) patients,
      mainly those with a prophylactic indication (P = 0.005). However, the rates of
      complications (58%) and inefficacy (27%) of reversion surgery were high.
      CONCLUSION: LTS is effective in the elimination and prevention of clinically
      intractable aspiration. The procedure is potentially reversible. However, the
      frequency of complications for both LTS and reversion surgery is significant.

PMID- 17011420
TI  - Adenoidectomy: long-term follow-up.
AB  - OBJECTIVE: To assess the long-term (3-5 years) success of adenoidectomy and
      reasons for unsatisfactory results. STUDY DESIGN AND SETTING: The parents of all
      children who underwent adenoidectomy alone at a major tertiary center from 1998
      to 2000 were asked to complete a questionnaire assessing their child's well-being
      and symptomatology 3-5 years after surgery; some were invited for follow-up.
      Symptom improvement, persistent symptoms, and adenoid regrowth were evaluated.
      RESULTS: Among the 206 parents who complied, 74%-87% reported improvement in all
      main symptoms: nasal obstruction, snoring, chronic rhinorrhea, hyponasal speech,
      and obstructive sleep disorder. At follow-up (n = 36), the symptomatic patients
      had significantly more anatomic nasal abnormalities (P = 0.01) and a higher rate
      of significant adenoid enlargement (P = 0.08), 3 patients (19%) vs none (0%).
      CONCLUSIONS AND SIGNIFICANCE: Adenoidectomy alone is satisfactory treatment for
      nasal obstruction and obstructive sleep apnea in selected children. Though some
      adenoid regrowth is not rare, clinically significant adenoid regrowth is
      infrequent. Persistent or recurrent symptoms are attributable mainly to nasal
      pathology.

PMID- 17011421
TI  - Thyroid cancer in children: management and outcome experience of a referral
      center.
AB  - OBJECTIVE: To shed light on the discrepancy between the advanced stage at
      presentation and high recurrence rate of well-differentiated thyroid cancer in
      children and the overall good survival. DESIGN AND METHODS: The files of 75
      children with well-differentiated thyroid cancer treated from 1954 to 2001 in a
      major tertiary-care hospital were reviewed for disease course, management, and
      outcome. RESULTS: Sixty patients (80%) had positive neck metastases with
      involvement of central compartment lymph nodes in all, lateral neck nodes in 36,
      and distant metastases in 4. Sixty-seven patients underwent total thyroidectomy
      with adjuvant radioiodine treatment and 8 underwent hemithyroidectomy; all had
      concomitant neck treatment. The rate of local (5%) and neck (9%) recurrence was
      similar to the total rate reported in adults. Total thyroidectomy led to a
      significantly lower recurrence rate (7.5%) than hemithyroidectomy (38%; P <
      0.005). Type of neck dissection did not affect recurrence or appearance of
      distant metastases. All deaths (n = 2) were due to distant metastases, whereas
      30% of adult deaths are due to local or neck disease. CONCLUSIONS: The treatment
      of choice for well-differentiated thyroid cancer in young patients is total
      thyroidectomy. Neither regional disease at presentation nor recurrences affect
      survival.

PMID- 17011422
TI  - Effects of ototopic steroid and NSAIDS in clearing middle ear effusion in an
      animal model.
AB  - OBJECTIVE: A model of otitis media with effusion (OME) has been developed in the
      Sprague-Dawley (SD) rat. This model was used to study the effects of an ototopic
      steroid and nonsteroidal anti-inflammatory drug (NSAID) on lipopolysaccharide
      (LPS)-induced OME. STUDY DESIGN: Twenty-six rats were randomized into 4 groups:
      saline solution, LPS, NSAID + LPS, and steroids + LPS. Test substance was
      injected into the middle ear at 0, 2, and 4 hours. The effusion was collected at
      2, 4, and 6 hours. Statistical analysis of effusion volume and albumin
      concentration was performed. RESULTS: The LPS group demonstrated statistically
      significant increase in both effusion volume and albumin concentration compared
      with saline solution. Intergroup comparison revealed significantly less effusion
      volume in the steroid group and less albumin concentration in the NSAID group
      when compared with the LPS group. CONCLUSIONS: Transtympanic steroid reduced LPS
      induced middle ear effusion while NSAID reduced albumin concentration in the rat
      model. SIGNIFICANCE: Our results lend support to the current use of anti
      inflammatory ototopicals in the treatment of inflammatory middle ear disease.

PMID- 17011423
TI  - Management of vocal paralysis: a comparison of adult and pediatric practices.
AB  - OBJECTIVE: To compare practices of the American Broncho-Esophagological
      Association (ABEA) membership regarding the evaluation and management of
      unilateral vocal fold motion impairment (UVFMI) in adult versus pediatric
      populations. STUDY DESIGN AND SETTING: An 18-item adult survey and 16-item
      pediatric survey were administered to ABEA members. RESULTS: Seventy-six adult
      (31%) and 35 pediatric surveys (43%) were completed. Key differences are
      highlighted. With respect to etiology, the most common reported childhood cause
      is idiopathic; adults more often suffer iatrogenic paralysis. Children more
      commonly experience reflux disease, feeding difficulties, and choking. Preferred
      testing involves flexible laryngoscopy and chest x-ray; however, laboratory tests
      are carried out less often in children (51% vs 71%) and medical intervention is
      advocated by fewer pediatric practitioners (39% vs 57%). CONCLUSION: Significant
      disparities exist in the etiology, presenting symptoms, diagnostic testing, and
      medical treatment between children and adults with UVFMI. SIGNIFICANCE:
      Clinicians' perceptions regarding UVFMI may reflect the differing impact of vocal
      paralysis in the pediatric versus adult populations.

PMID- 17011425
TI  - Evaluating the validity of the Voice Handicap Index-10 (VHI-10) among Hebrew
      speakers.
AB  - OBJECTIVE: To evaluate the validity of a translated version of the Voice Handicap
      Index-10 (VHI-10). STUDY DESIGN AND SETTING: In a parallel group design, 221
      patients with different laryngeal pathologies and 172 people with no laryngeal
      pathology completed a Hebrew version of the VHI-10. Validity and reliability were
      assessed as well as group differences. RESULTS: Statistical analyses demonstrated
      high reliability values (Cronbach's Alpha r = 0.949). Responses were not affected
      by age (P = 0.373) or gender (P = 0.360). The control group received
      significantly lower scores than all pathological groups (P < 0.05). Within the
      pathological groups, the "neurogenic" and "mucosa irregularity" groups were rated
      higher than all other pathological groups (P < 0.05). CONCLUSION: The VHI-10
      questionnaire maintains its validity and reliability across translation to
      Hebrew. Moreover, although the VHI-10 is essentially a unidimensional tool, it
      provides partial information on the 3 subjective dimensions of the full VHI.

PMID- 17011426
TI  - Practical guides to efficient life-long learning.

PMID- 17011424
TI  - Objective measurement of vocal fatigue in classical singers: a vocal dosimetry
      pilot study.
AB  - OBJECTIVES: To collect objective vibration dose data on singers and relate them
      to subjective measurements of vocal fatigue. STUDY DESIGN AND SETTING: Seven
      subjects completed a 2-week study period. The National Center for Voice and
      Speech (NCVS) dosimeter recorded vocal load, soft phonation tasks, and subjective
      soft voice ratings. Three vocal doses (time, distance, and cycle) were measured
      in classical singers' larynges during an intensive practice period. RESULTS:
      Spikes in vocal load are reflected as harsher subjective ratings on the same day
      as well as 24-72 hours later. When at least 48 hours of vocal rest occurred
      before a vocal load, improved subjective evaluations were seen after the load.
      CONCLUSIONS: The NCVS dosimeter appears to be an effective tool for data
      collection on prolonged use of the voice. SIGNIFICANCE: This is the first multi
      day study comparing objective and subjective data on vocal fatigue in a group of
      professional singers.

PMID- 17011427
TI  - Transnasal esophagoscopy: state of the art.

PMID- 17011428
TI  - What's new in skull base medicine and surgery? Skull Base Committee Report.

PMID- 17011429
TI  - A novel method to remove worn-out abutment from fixture of bone-anchored hearing
      aid (BAHA).

PMID- 17011430
TI  - Da Vinci robot-assisted endocrine surgery: novel applications in otolaryngology.

PMID- 17011431
TI  - Malakoplakia in nasal vestibule.

PMID- 17011432
TI  - Radiologic findings in sinonasal myiasis.

PMID- 17011433
TI  - Sporadic Burkitt's lymphoma presenting with multiple cranial neuropathies.

PMID- 17011434
TI  - Angiolipoma of the neck.

PMID- 17011435
TI  - Cardiac metastasis in a laryngeal carcinoma and associated electrocardiographic
      changes.

PMID- 17011436
TI  - Elderly woman with hypercalcemia and neck mass.

PMID- 17011437
TI  - Tubercular otitis media in children.

PMID- 17011438
TI  - Oncogenic osteomalacia caused by phosphaturic mesenchymal tumor of the temporal
      bone.

PMID- 17011439
TI  - Spontaneous intracranial hypotension mimicking Meniere's disease.

PMID- 17011440
TI  - Optically guided stereotactic radiotherapy for facial nerve paralysis secondary
      to occult malignant neoplasms.

PMID- 17011441
TI  - Infection of true vocal fold cyst with Aspergillus.

PMID- 17011442
TI  - ReVOLT: radiation-enhanced viral oncolytic therapy.
AB  - Viral oncolytic therapy has been pursued with renewed interest as the molecular
      basis of carcinogenesis and viral replication has been elucidated. Genetically
      engineered, attenuated viruses have been rationally constructed to achieve a
      therapeutic index in tumor cells compared with surrounding normal tissue. Many of
      these attenuated mutant viruses have entered clinical trials. Here we review the
      preclinical literature demonstrating the interaction of oncolytic viruses with
      ionizing radiation and provides a basis for future clinical trials.

PMID- 17011443
TI  - Whole-pelvis, "mini-pelvis," or prostate-only external beam radiotherapy after
      neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation
      Therapy Oncology Group 9413 trial.
AB  - PURPOSE: The Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a
      better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT)
      compared with prostate-only (PO) RT. This secondary analysis was undertaken to
      determine whether "mini-pelvis" (MP; defined as > or = 10 x 11 cm but < 11 x 11
      cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT.
      To avoid a timing bias, this analysis was limited to patients receiving
      neoadjuvant and concurrent hormonal therapy (N&CHT) in Arms 1 and 2 of the study.
      METHODS AND MATERIALS: Eligible patients had a risk of lymph node (LN)
      involvement > 15%. Neoadjuvant and concurrent hormonal therapy (N&CHT) was
      administered 2 months before and during RT for 4 months. From April 1, 1995, to
      June 1, 1999, a group of 325 patients were randomized to WP RT + N&CHT and
      another group of 324 patients were randomized to receive PO RT + N&CHT. Patients
      randomized to PO RT were dichotomized by median field size (10 x 11 cm), with the
      larger field considered an "MP" field and the smaller a PO field. RESULTS: The
      median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p
      = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and
      PO fields, respectively. There was no association between field size and late
      Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT
      complications correlated with increasing field size. CONCLUSIONS: This subset
      analysis demonstrates that RT field size has a major impact on PFS, and the
      findings support comprehensive nodal treatment in patients with a risk of LN
      involvement of > 15%.

PMID- 17011444
TI  - Intensity-modulated radiotherapy improves lymph node coverage and dose to
      critical structures compared with three-dimensional conformal radiation therapy
      in clinically localized prostate cancer.
AB  - PURPOSE: The aim of this study was to quantify gains in lymph node coverage and
      critical structure dose reduction for whole-pelvis (WP) and extended-field (EF)
      radiotherapy in prostate cancer using intensity-modulated radiotherapy (IMRT)
      compared with three-dimensional conformal radiotherapy (3DCRT) for the first
      treatment phase of 45 Gy in the concurrent treatment of lymph nodes and prostate.
      METHODS AND MATERIALS: From January to August 2005, 35 patients with localized
      prostate cancer were treated with pelvic IMRT; 7 had nodes defined up to L5-S1
      (Group 1), and 28 had nodes defined above L5-S1 (Group 2). Each patient had 2
      plans retrospectively generated: 1 WP 3DCRT plan using bony landmarks, and 1 EF
      3DCRT plan to cover the vascular defined volumes. Dose-volume histograms for the
      lymph nodes, rectum, bladder, small bowel, and penile bulb were compared by
      group. RESULTS: For Group 1, WP 3DCRT missed 25% of pelvic nodes with the
      prescribed dose 45 Gy and missed 18% with the 95% prescribed dose 42.75 Gy,
      whereas WP IMRT achieved V(45 Gy) = 98% and V(42.75 Gy) = 100%. Compared with WP
      3DCRT, IMRT reduced bladder V(45 Gy) by 78%, rectum V(45 Gy) by 48%, and small
      bowel V(45 Gy) by 232 cm3. EF 3DCRT achieved 95% coverage of nodes for all
      patients at high cost to critical structures. For Group 2, IMRT decreased bladder
      V(45 Gy) by 90%, rectum V(45 Gy) by 54% and small bowel V(45 Gy) by 455 cm3
      compared with EF 3DCRT. CONCLUSION: In this study WP 3DCRT missed a significant
      percentage of pelvic nodes. Although EF 3DCRT achieved 95% pelvic nodal coverage,
      it increased critical structure doses. IMRT improved pelvic nodal coverage while
      decreasing dose to bladder, rectum, small bowel, and penile bulb. For patients
      with extended node involvement, IMRT especially decreases small bowel dose.

PMID- 17011445
TI  - Accelerated partial-breast irradiation using proton beams: initial clinical
      experience.
AB  - PURPOSE: We present our initial clinical experience with proton, three
      dimensional, conformal, external beam, partial-breast irradiation (3D-CPBI).
      METHODS AND MATERIALS: Twenty patients with Stage I breast cancer were treated
      with proton 3D-CPBI in a Phase I/II clinical trial. Patients were followed at 3
      to 4 weeks, 6 to 8 weeks, 6 months, and every 6 months thereafter for recurrent
      disease, cosmetic outcome, toxicity, and patient satisfaction. RESULTS: With a
      median follow-up of 12 months (range, 8-22 months), no recurrent disease has been
      detected. Global breast cosmesis was judged by physicians to be good or excellent
      in 89% and 100% of cases at 6 months and 12 months, respectively. Patients rated
      global breast cosmesis as good or excellent in 100% of cases at both 6 and 12
      months. Proton 3D-CPBI produced significant acute skin toxicity with moderate to
      severe skin color changes in 79% of patients at 3 to 4 weeks and moderate to
      severe moist desquamation in 22% of patients at 6 to 8 weeks. Telangiectasia was
      noted in 3 patients. Three patients reported rib tenderness in the treated area,
      and one rib fracture was documented. At last follow-up, 95% of patients reported
      total satisfaction with proton 3D-CPBI. CONCLUSIONS: Based on our study results,
      proton 3D-CPBI offers good-to-excellent cosmetic outcomes in 89% to 100% of
      patients at 6-month and 12-month follow-up and nearly universal patient
      satisfaction. However, proton 3D-CPBI, as used in this study, does result in
      significant acute skin toxicity and may potentially be associated with late skin
      (telangiectasia) and rib toxicity. Because of the dosimetric advantages of proton
      3D-CPBI, technique modifications are being explored to improve acute skin
      tolerance.

PMID- 17011446
TI  - Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: long
      term results of phase III clinical trial.
AB  - PURPOSE: To update 5-year results of a previously published study on special 7
      days-a-week fractionation continuous accelerated irradiation (CAIR) for head-and
      neck cancer patients. METHODS AND MATERIALS: One hundred patients with squamous
      cell carcinoma of head and neck in Stage T(2-4)N(0-1)M(0) were randomized between
      two definitive radiation treatments: accelerated fractionation 7 days a week
      including weekends (CAIR) and conventional 5 days a week (control). Hence the
      overall treatment time was 2 weeks shorter in CAIR. RESULTS: Five-year local
      tumor control was 75% in the CAIR group and 33% in the control arm (p < 0.00004).
      Tumor-cure benefit corresponded with significant improvement in disease-free
      survival and overall survival rates. Confluent mucositis was the main acute
      toxicity, with the incidence significantly higher in CAIR patients than in
      control (respectively, 94% vs. 53%). When 2.0-Gy fractions were used, radiation
      necrosis developed in 5 patients (22%) in the CAIR group as a consequential late
      effect (CLE), but when fraction size was reduced to 1.8 Gy no more CLE occurred.
      Actuarial 5-year morbidity-free survival rate was similar for both treatments.
      CONCLUSIONS: Selected head-and-neck cancer patients could be treated very
      effectively with 7-days-a-week radiation schedule with no compromise of total
      dose and with slight 10% reduction of fraction dose (2 Gy-1.8 Gy), which article
      gives 1 week reduction of overall treatment time compared with standard 70 Gy in
      35 fractions over 47-49 days. Although this report is based on the relatively
      small group of patients, its results have encouraged us to use CAIR fractionation
      in a standard radiation treatment for moderately advanced head-and-neck cancer
      patients.

PMID- 17011447
TI  - Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor
      burden, and metabolic activity in advanced nasopharyngeal carcinoma.
AB  - PURPOSE: Plasma Epstein-Barr virus DNA (pEBV DNA) is an important prognostic
      marker in nasopharyngeal carcinoma (NPC). This study tested the hypotheses that
      pEBV DNA reflects tumor burden and metabolic activity by evaluating its
      relationship with tumor volume and 18F-fluorodeoxyglucose (18F-FDG) uptake in
      NPC. METHODS AND MATERIALS: Pre-treatment pEBV DNA analysis, 18F-FDG positron
      emission tomography-computed tomography scan (PET-CT) and magnetic resonance
      imaging (MRI) of the head and neck were performed in 57 patients. Net volume
      (cm3) of the primary tumor (T(vol)) and regional nodes (N(vol)) were quantified
      on MRI. 18F-FDG uptake was expressed as the maximum standardized uptake value
      (SUV(max)) at the primary tumor (T(suv)) and regional nodes (N(suv)). Lesions
      with SUV(max) > or = 2.5 were considered malignant. Relationship between
      SUV(max), natural logarithm (log) of pEBV DNA, and square root (sq) of MRI
      volumes was analyzed using the Wilcoxon test. A linear regression model was
      constructed to test for any interaction between variables and disease stage.
      RESULTS: Log-pEBV DNA showed significant correlation with sq-T(vol) (r = 0.393),
      sq-N(vol) (r = 0.452), total tumor volume (sq-Total(vol) = T(vol) + N(vol), r =
      0.554), T(suv) (r = 0.276), N(suv) (r = 0.434), and total SUV(max) (Total(suv) =
      T(suv) + N(suv), r = 0.457). Likewise, sq-T(vol) was correlated to T(suv) (r =
      0.426), and sq-N(vol) with N(suv) (r = 0.651). Regression analysis showed that
      only log-pEBV DNA was significantly associated with sq-Total(vol) (p < 0.001;
      parameter estimate = 8.844; 95% confidence interval = 3.986-13.703), whereas Sq
      T(vol) was significantly associated with T(suv) (p = 0.002; parameter estimate =
      3.923; 95% confidence interval = 1.498-6.348). CONCLUSION: This study supports
      the hypothesis that cell-free plasma EBV DNA is a marker of tumor burden in EBV
      related NPC.

PMID- 17011448
TI  - Magnetic resonance imaging of retropharyngeal lymph node metastasis in
      nasopharyngeal carcinoma: patterns of spread.
AB  - PURPOSE: To investigate the incidence, distribution, and spread pattern of
      retropharyngeal lymph node (RLN) involvement in patients with nasopharyngeal
      carcinoma (NPC) by using magnetic resonance imaging (MRI). METHODS AND MATERIALS:
      The MR images of 275 patients with newly diagnosed NPC were reviewed
      retrospectively. Nodes were classified as metastatic based on size criteria, the
      presence of nodal necrosis, and extracapsular spread. RESULTS: Retropharyngeal
      lymph node involvement was detected in 175 (63.6%) patients. Metastatic RLNs were
      seen at the following levels: occipital bone, 24 (9.6%) nodes; C1, 157 (62.5%)
      nodes; C1/2, 40 (15.9%) nodes; C2, 27 (10.8%) nodes; C2/3, 1 (0.4%) node; and C3,
      2 (0.8%) nodes. The incidence of RLN involvement was equal to the incidence of
      cervical lymph node involvement (81.4% vs. 81.4%) in 215 patients with nodal
      metastases. A significantly higher incidence of metastatic RLNs was observed in
      the presence of oropharynx, prestyloid parapharyngeal space, post-styloid
      parapharyngeal space, longus colli muscle, medial pterygoid muscle, levator
      muscle of velum palatini, tensor muscle of velum palatini, Level II node, Level
      III node, and Level V node involvement. A significantly lower incidence of
      metastatic RLNs was found in T1, N0, and Stage I disease. Conversely, no
      significant difference in the incidence of metastatic RLNs was observed between
      T1, 2, and, 3; N2 and N3; or Stage II, III, and IV disease. CONCLUSIONS: There is
      an orderly decrease in the incidence of metastatic lateral RLNs from the C1 to C3
      level. Metastatic RLNs associate well with involvement of certain structures in
      early stage primary tumors and lymph node metastases of the upper jugular chain
      (Level II, Level III nodes) and the posterior triangle (Level V nodes). Both RLNs
      and cervical Level II nodes appear to be the first-echelon nodes in NPC.

PMID- 17011449
TI  - Gemcitabine and cisplatin in a concomitant alternating chemoradiotherapy program
      for locally advanced head-and-neck cancer: a pharmacology-guided schedule.
AB  - PURPOSE: Administration of gemcitabine together with cisplatin at cytotoxic doses
      in a chemoradiotherapy regimen is hampered by a high degree of local toxicity.
      Using the pharmacologic properties of the drug we designed a modified schedule
      aimed at reducing toxicity while preserving activity. METHODS AND MATERIALS:
      Patients with squamous cell carcinomas of the oral cavity, pharynx and larynx,
      bulky T4, and/or N2 to N3 were eligible. Gemcitabine was administered at a dose
      of 800 mg/m2 on Days 1 and 12 and cisplatin at a dose of 20 mg/m2 on Days 2 to 5,
      every 21 days for 3 courses. Radiotherapy, delivered with standard fractionation,
      was given on Days 8 to 12 and 15 to 19 and was repeated 3 times up to a total
      dose of > or = 60 Gy. RESULTS: A total of 28 patients were selected. Grade 3 to 4
      stomatitis was recorded in 25 patients (89%). Thirteen patients (46%) experienced
      Grade 3 to 4 neutropenia. Febrile neutropenia occurred in 8 patients (29%) and in
      2 was complicated by infection and death. The overall complete response rate was
      79%. At a median follow up of 71 months, 11 patients had a locoregional relapse
      (3-year locoregional control, 64%); 6 patients had distant metastases, among whom
      only 2 were without locoregional recurrence. The 3-year progression-free survival
      is 39% and 3-year overall survival has been 43%. CONCLUSION: The schedule
      modification did not attenuate local toxicity. Moreover, infections and
      especially pneumonia, were a major problem. The high activity of gemcitabine when
      combined with radiotherapy would most likely be better exploited in the context
      of modified radiation schemes.

PMID- 17011450
TI  - Intra-patient variability of tumor volume and tumor motion during conventionally
      fractionated radiotherapy for locally advanced non-small-cell lung cancer: a
      prospective clinical study.
AB  - PURPOSE: The aim of this study was to investigate the change in tumor volume,
      motion, and breathing frequency during a course of radiotherapy, for locally
      advanced non-small-cell lung cancer. METHODS AND MATERIALS: A total of 23
      patients underwent computed tomography-positron emission tomography (CT-PET) and
      respiration correlated CT scans before treatment, which was repeated in the first
      and second weeks after the start of radiotherapy. Patients were treated with an
      accelerated fractionation schedule, 1.8 Gy twice a day, with a total tumor dose
      depending on preset dose constraints for the lungs and spinal cord. RESULTS: A
      striking heterogeneity of tumor volume changes was observed at all time points.
      In some patients the volume decreased >30% (3/23), whereas in others the volume
      increased >30% (4/24); but for the majority of patients (16/23), the tumor volume
      changed only slightly (<30%). No significant changes in average tumor motion or
      breathing frequencies were observed during treatment. Although a number of
      changes in individual tumor motion were seen, only in 1 patient would this have
      led to an increase of the internal margin >1 mm in 1 direction, 1 week after the
      start of treatment, and in 3 patients for 1 direction, 2 weeks after the start of
      the treatment. CONCLUSION: In this patients in this study, a large variability in
      changes in tumor volume was observed. This underscores the need for repeated
      imaging during the course of radiotherapy. However, the changes in tumor motion
      are small, which indicates that repeated respiration correlated CT does not
      appear to be necessary.

PMID- 17011451
TI  - Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in
      patients with locally advanced rectal cancer.
AB  - PURPOSE: The aim of this study was to determine the efficacy of capecitabine
      (Xeloda), an oral fluoropyrimidine, as a radiosensitizer in the neoadjuvant
      treatment of locally advanced rectal cancer (LARC). METHODS AND MATERIALS: We
      conducted a phase II study of capecitabine (825 mg/m2 orally, twice daily
      continuous) with radiotherapy (52.5 Gy/30 fractions to the primary tumor and
      perirectal nodes) in 54 patients with LARC (node-negative > or = T3 or any node
      positive tumor) staged by endoscopic ultrasound (EUS). The primary endpoint was
      pathologic response rate; secondary endpoints included toxicity profiles and
      survival parameters. RESULTS: Of the 54 patients (median age, 56.7 years; range,
      21.3-78.7 years; male:female ratio, 1.7; Eastern Cooperative Oncology Group
      performance status 0-1: 100%), 51 patients (94%) had T3N0 or T3N1 disease by EUS.
      Surgery was not performed in 3 patients; 2 of these patients had metastatic
      disease, and the third patient refused after a complete clinical response. Of the
      51 patients evaluable for pathologic response, 9 patients (18%) achieved complete
      response, and 12 patients (24%) had microscopic residual disease (< 10% viable
      cells). In addition, 26 patients of all 54 patients (51%) achieved T-downstaging,
      and 15 patients of 29 patients (52%) achieved N-downstaging. Grade 3/4 toxicities
      were radiation dermatitis (9%) and diarrhea (2%). Sphincter preservation rate for
      tumor < or = 5 cm from the anal verge was 67% (18/27). CONCLUSION: This regimen
      of radiotherapy plus capecitabine is well tolerated and is more convenient than
      protracted venous infusion of 5-FU. The pathologic response rate is comparable to
      our previous experience using protracted venous infusion 5-FU for LARC.

PMID- 17011452
TI  - External-beam radiotherapy for localized extrahepatic cholangiocarcinoma.
AB  - PURPOSE: The role of radiation therapy (RT) in extrahepatic cholangiocarcinoma
      (EHCC) is not clear and only limited reports exist on the use of this modality.
      We have reviewed our institutional experience to determine the pattern of failure
      in patients after potentially curative resection and the expected outcomes after
      adjuvant RT and in unresectable patients. METHODS AND MATERIALS: After
      institutional review board approval, 81 patients diagnosed with EHCC (gallbladder
      28, distal bile duct 24, hilar 29) between June 1986 and December 2004 were
      identified and their records reviewed. Twenty-eight patients (35%) underwent
      potentially curative resection with R0/R1 margins. Fifty-two patients (64%) were
      unresectable or underwent resection with macroscopic residual disease (R2). All
      patients received three-dimensional planned megavoltage RT. The dose for each
      patient was converted to the equivalent total dose in a 2 Gy/fraction, using the
      linear-quadratic formalism and alpha/beta ratio of 10. The median dose delivered
      was 58.4 Gy (range, 23-88.2 Gy). 54% received concomitant chemotherapy. RESULTS:
      With a median follow-up time of 1.2 years (range, 0.1-9.8 years) 75 patients
      (93%) have died. Median overall survival (OS) and progression-free survival (PFS)
      were 14.7 (95% CI, 13.1-16.3) and 11 (95% CI, 7.6-13.2) months, respectively.
      There was no difference among the three disease sites in OS (p = 0.70) or PFS (p
      = 0.80). Complete resection (R0) was the only predictive factor significantly
      associated with increase in both OS and PFS (p = 0.002), and there was no
      difference in outcomes between R1 and R2 resections. The first site of failure
      was predominantly locoregional (68.8% of all failures). CONCLUSION: Local failure
      is a major problem in EHCC, suggesting the need for more intense radiation
      schedules and better radiosensitizing strategies. Because R1 resection appears to
      convey no benefit, it appears that surgery should be contemplated only when an R0
      resection is likely. Borderline-resectable patients might be better served by
      neoadjuvant therapy.

PMID- 17011453
TI  - Prospective comparison of computed tomography and magnetic resonance imaging for
      liver cancer delineation using deformable image registration.
AB  - PURPOSE: The aim of this study was to compare magnetic resonance imaging (MRI)
      with computed tomography (CT) for liver cancer tumor definition for high
      precision radiotherapy planning. METHODS AND MATERIALS: Diagnostic quality MRI
      scans and triphasic CT scans, with the liver immobilized in exhale, were obtained
      at the time of radiation planning for 26 patients with unresectable liver
      metastases (n = 8), hepatocellular carcinoma (n = 10), and cholangiocarcinoma (n
      = 8). On the CT and MRI series best demonstrating the tumor, the liver and gross
      tumor volumes (GTVs) were contoured, and intrahepatic anatomic reference points
      were identified. Deformable registration was used to register the liver from the
      CT with that from the MRI. RESULTS: A difference in the number of tumor foci was
      seen on CT vs. MRI in 5 patients with hepatocellular carcinoma: MRI showed more
      foci in 3 patients, CT in 2. After deformable registration of the livers, the
      population median of the average distance between the CT tumor surface and MRI
      tumor surface was 3.7 mm (2.2-21.3 mm). The median percentage of tumor surface
      area that differed by > or = 5 mm was 26% (1-86%). Median percentage concordance
      volumes were 81% (77-86%) in metastases, 77% (60-88%) in hepatocellular carcinoma
      and 64% (25-85%) in cholangiocarcinoma. CONCLUSION: Differences between MRI
      defined liver cancer GTVs and CT-defined GTVs can be substantial and are more
      common in primary liver cancer.

PMID- 17011454
TI  - RPA classification has prognostic significance for surgically resected single
      brain metastasis.
AB  - PURPOSE: To retrospectively evaluate prognostic factors that correlate with
      overall survival among patients with a surgically resected single brain
      metastasis. METHODS AND MATERIALS: An Institutional Review Board-approved
      database of the Cleveland Clinic Brain Tumor Institute was queried for patients
      with a single brain metastasis treated by surgical resection between February
      1984 and January 2004. The primary endpoint was overall survival from the date of
      surgery by the Kaplan-Meier method. RESULTS: A total of 271 patients were
      included. Statistically significant variables for improved survival on
      multivariate analysis included age <65 years, lack of extracranial metastases,
      control of primary tumor, histology (non-small-cell lung carcinoma), and use of
      stereotactic radiosurgery. The median survival for all patients was 10.2 months.
      Survival of patients in recursive partitioning analysis (RPA) class 1 was better
      (21.4 months) than those in RPA class 2 (9.0 months, p < 0.001), RPA class 3 (8.9
      months, p = 0.15), or the combined group of RPA classes 2 and 3 (9.0 months, p <
      0.001). Patients had a median survival of 10.6 months after documented gross
      total resection and 8.7 months after subtotal resection, which approached
      statistical significance (p = 0.07). Those who were treated with stereotactic
      radiosurgery had a median survival of 17.1 months, which was greater than
      patients who were not treated with stereotactic radiosurgery (8.9 months, p =
      0.006). CONCLUSIONS: This analysis supports the prognostic significance of the
      RPA classification in patients with a single brain metastasis who undergo
      surgical resection and adjuvant therapy. RPA class 1 patients have a very
      favorable prognosis with a median survival of 21.4 months.

PMID- 17011455
TI  - Incidence of sarcoma in patients treated with fast neutrons.
AB  - PURPOSE: The aim of this study is to report the incidence of soft tissue sarcoma
      in a large group of patients treated with fast neutrons. METHODS: A systematic
      review was conducted of long-term follow-up after trials of fast neutron therapy
      for cancers at various sites. The study took place at Edinburgh Cancer Centre,
      Western General Hospital, Edinburgh, Scotland, United Kingdom. From 1977 to 1984,
      620 patients were treated using fast neutrons in the MRC cyclotron unit in
      Edinburgh. Most of these were treated within randomized controlled trials. Follow
      up was maintained in all except 2 patients, who left the area to return abroad.
      The main outcome measure was the incidence of new soft-tissue sarcomas during
      long-term follow-up. RESULTS: Three cases of sarcoma, developing within the
      treatment volume, were observed in a small group of patients treated some years
      earlier using fast neutrons. This incidence was 111 times what would have been
      expected in the normal population and 15 times the incidence in a comparable
      photon-treated group of patients. CONCLUSION: The long-term incidence of sarcomas
      in patients previously treated with fast neutrons is significant.

PMID- 17011456
TI  - The utility of 18F-fluorodeoxyglucose positron emission tomography for early
      diagnosis of radiation-induced myocardial damage.
AB  - PURPOSE: We evaluated the clinical significance of focal increased uptake in the
      basal myocardium on F-fluorodeoxyglucose positron emission tomography (FDG-PET)
      in patients with esophageal cancer after radiotherapy. METHODS AND MATERIALS:
      Between August 2004 and July 2005, a total of 64 patients who had been irradiated
      for thoracic esophageal cancer underwent FDG-PET at least three months after the
      completion of chemoradiotherapy. Some patients showed increased FDG uptake in the
      basal portion of the myocardium. To clarify the clinical significance of these
      findings, further examinations of hearts were performed. The dose distribution in
      the myocardium with high FDG uptake was also analyzed retrospectively. RESULTS:
      Thirteen (20.3%) of the 64 patients showed high FDG uptake in the basal
      myocardium corresponding to the irradiated fields compared with FDG uptake in the
      myocardium outside the irradiated fields. Eight of the 13 patients consented to
      undergo examinations of the heart. Five of those eight patients showed low 123I
      BMIPP uptake and four showed low 201TlCl uptake in the myocardium corresponding
      with high FDG uptake regions. In two patients, delayed enhancement was found in
      some parts of the area with high FDG uptake on Gd-DTPA magnetic resonance imaging
      (MRI), and the delay-enhanced lesion showed hypokinesia on cine-MRI in one
      patient. CONCLUSIONS: FDG-PET often shows focal increased uptake in the basal
      myocardium after radiotherapy for esophageal cancer. This finding indicates the
      possibility of radiation-induced cardiac damage, and cardiac function and
      symptoms of such patients should be followed carefully.

PMID- 17011458
TI  - Effects of fractionated radiation on the brain vasculature in a murine model:
      blood-brain barrier permeability, astrocyte proliferation, and ultrastructural
      changes.
AB  - PURPOSE: Radiation therapy of CNS tumors damages the blood-brain barrier (BBB)
      and normal brain tissue. Our aims were to characterize the short- and long-term
      effects of fractionated radiotherapy (FRT) on cerebral microvasculature in mice
      and to investigate the mechanism of change in BBB permeability in mice. METHODS
      AND MATERIALS: Intravital microscopy and a cranial window technique were used to
      measure BBB permeability to fluorescein isothiocyanate (FITC)-dextran and
      leukocyte endothelial interactions before and after cranial irradiation. Daily
      doses of 2 Gy were delivered 5 days/week (total, 40 Gy). We immunostained the
      molecules to detect the expression of glial fibrillary acidic protein and to
      demonstrate astrocyte activity in brain parenchyma. To relate the permeability
      changes to endothelial ultrastructural changes, we used electron microscopy.
      RESULTS: Blood-brain barrier permeability did not increase significantly until 90
      days after FRT, at which point it increased continuously until 180 days post-FRT.
      The number of adherent leukocytes did not increase during the study. The number
      of astrocytes in the cerebral cortex increased significantly; vesicular activity
      in endothelial cells increased beginning 90 days after irradiation, and most
      tight junctions stayed intact, although some were shorter and less dense at 120
      and 180 days. CONCLUSIONS: The cellular and microvasculature response of the
      brain to FRT is mediated through astrogliosis and ultrastructural changes,
      accompanied by an increase in BBB permeability. The response to FRT is delayed as
      compared with single-dose irradiation treatment, and does not involve leukocyte
      adhesion. However, FRT induces an increase in the BBB permeability, as in the
      case of single-dose irradiation.

PMID- 17011457
TI  - Effect of downregulation of survivin expression on radiosensitivity of human
      epidermoid carcinoma cells.
AB  - PURPOSE: The expression of survivin, a member of the inhibitor-of-apoptosis
      protein family, is elevated in many types of human cancer. High survivin
      expression has been associated with poor patient prognosis and tumor resistance
      to chemotherapy and radiotherapy. The purpose of this study was to compare the
      radiosensitizing effects of five agents that target survivin on their relative
      ability to downregulate survivin expression. METHODS AND MATERIALS: The human
      epidermoid carcinoma cell line A431 was treated with adenoviral-mediated wild
      type p53, antisense to survivin, the mitogen-activated protein kinase inhibitor
      PD98059, the cyclin-dependent kinase inhibitor Purvalanol A, or the histone
      deacetylase inhibitor trichostatin A. The radiosensitizing effects of these
      treatments were determined by clonogenic survival curve analysis and their
      abilities to suppress survivin expression by Western blot analysis. RESULTS: All
      the strategies were shown to radiosensitize A431 cells. This effect correlated
      with their abilities to downregulate survivin. CONCLUSION: Expression of survivin
      appears to confer a radioresistant phenotype that can be overcome using several
      clinically achievable strategies that target survivin either specifically or
      nonspecifically.

PMID- 17011460
TI  - Daily variations in delivered doses in patients treated with radiotherapy for
      localized prostate cancer.
AB  - PURPOSE: The aim of this work was to study the variations in delivered doses to
      the prostate, rectum, and bladder during a full course of image-guided external
      beam radiotherapy. METHODS AND MATERIALS: Ten patients with localized prostate
      cancer were treated with helical tomotherapy to 78 Gy at 2 Gy per fraction in 39
      fractions. Daily target localization was performed using intraprostatic fiducials
      and daily megavoltage pelvic computed tomography (CT) scans, resulting in a total
      of 390 CT scans. The prostate, rectum, and bladder were manually contoured on
      each CT by a single physician. Daily dosimetric analysis was performed with dose
      recalculation. The study endpoints were D95 (dose to 95% of the prostate), rV2
      (absolute rectal volume receiving 2 Gy), and bV2 (absolute bladder volume
      receiving 2 Gy). RESULTS: For the entire cohort, the average D95 (+/-SD) was 2.02
      +/- 0.04 Gy (range, 1.79-2.20 Gy). The average rV2 (+/-SD) was 7.0 +/- 8.1 cc
      (range, 0.1-67.3 cc). The average bV2 (+/-SD) was 8.7 +/- 6.8 cc (range, 0.3-36.8
      cc). Unlike doses for the prostate, there was significant daily variation in
      rectal and bladder doses, mostly because of variations in volume and shape of
      these organs. CONCLUSION: Large variations in delivered doses to the rectum and
      bladder can be documented with daily megavoltage CT scans. Image guidance for the
      targeting of the prostate, even with intraprostatic fiducials, does not take into
      account the variation in actual rectal and bladder doses. The clinical impact of
      techniques that take into account such dosimetric parameters in daily patient set
      ups should be investigated.

PMID- 17011459
TI  - Poly(ADP-ribose) polymerase inhibition combined with irradiation: a dual
      treatment concept to prevent neointimal hyperplasia after endarterectomy.
AB  - PURPOSE: In a rat model of endarterectomy we investigated the potential role of
      the peroxynitrite-poly(ADP-ribose) polymerase (PARP) pathway in neointima
      formation and the effects of irradiation, pharmacologic inhibition of PARP, or
      combined pharmacologic inhibition of PARP and irradiation on vascular remodeling.
      METHODS AND MATERIALS: Carotid endarterectomy was performed by incision of the
      left carotid artery with removal of intima in Sprague-Dawley rats. Six groups
      were studied: sham-operated rats (n = 10), control endarterectomized rats (n =
      10), or endarterectomized rats irradiated with 15 Gy (n = 10), or treated with
      PARP inhibitor, INO-1001 (5 mg/kg/day) (n = 10), or with combined treatment with
      INO-1001 and irradiation with 5 Gy (n = 10) or with 15 Gy (n = 10). After 21
      days, neointima formation and vascular remodeling were assessed. RESULTS:
      Neointima formation after endarterectomy was inhibited by postoperative
      irradiation with 15 Gy and was attenuated by PARP inhibition. However, in
      parallel to inhibition of neointimal hyperplasia, activation of the peroxynitrite
      PARP pathway in the outer vessel wall layers was triggered by postoperative
      irradiation. Combined pharmacologic PARP inhibition and irradiation with 15 Gy
      significantly reduced both neointimal hyperplasia and activation of the
      peroxynitrite-PARP pathway in the outer vessel wall layers. Combination of PARP
      inhibition and irradiation with 5 Gy was less effective than both PARP inhibition
      or irradiation with 15 Gy alone. CONCLUSIONS: We conclude, that combined PARP
      inhibition and irradiation with 15 Gy may be a new dual strategy for prevention
      of restenosis after surgical vessel reconstruction: combining the strong
      antiproliferative effect of irradiation and ameliorating irradiation-induced side
      effects caused by excessive PARP activation.

PMID- 17011461
TI  - Dosimetric comparison of four target alignment methods for prostate cancer
      radiotherapy.
AB  - PURPOSE: The aim of this study was to compare the dosimetric consequences of 4
      treatment delivery techniques for prostate cancer patients treated with intensity
      modulated radiotherapy (IMRT). METHODS AND MATERIALS: During an 8-week course of
      radiotherapy, 10 patients underwent computed tomography (CT) scans 3 times per
      week (243 total) before daily treatment with a CT-linear accelerator. Treatment
      delivery was simulated by realigning a fixed-margin treatment plan on each CT
      scan and calculating doses. The alignment methods were those based on the
      following: skin marks, bony registration, ultrasonography (US), and in-room CT.
      For the last two methods, prostate was the alignment target. The dosimetric
      effects of these alignment methods on the prostate, seminal vesicles, rectum, and
      bladder were compared. The average daily minimum dose to 0.1 cm3 was used as the
      metric for target coverage. RESULTS: Skin and bone alignments provided acceptable
      prostate coverage for only 70% of patients, US alignment for 90%, and CT
      alignment for 100%. CT-based alignment of the prostate provided seminal vesicle
      (SV) coverage of > or = 69 Gy for all patients; US and bone alignments provided
      SV coverage of > or = 60 Gy. This SV coverage may be acceptable for early-stage
      cancer (equivalent SV dose = 55.8 Gy at 1.8 Gy per fraction), but unacceptable
      for late-stage cancer (SV dose = 75.6 Gy). At 75.6 Gy, the acceptable rate for SV
      coverage was 40% for skin and bone alignments, 70% for US, and 80% for CT.
      CONCLUSIONS: Direct target alignment methods (US and CT) provided better target
      coverage. CT-guided alignment provided the best and most consistent dosimetric
      coverage. A larger planning target volume margin is needed for SV coverage when
      the alignment target is the prostate.

PMID- 17011463
TI  - Optimization of the temporal pattern of radiation: an IMRT based study.
AB  - PURPOSE: To investigate how the temporal pattern of dose applied during a single
      intensity modulated radiation therapy (IMRT) fraction can be arranged to maximize
      or minimize cell kill. METHODS AND MATERIALS: Using the linear-quadratic repair
      time model and a simplified IMRT delivery pattern model, the surviving fraction
      of cells for a single fraction was calculated for all permutations of the dose
      delivery pattern for an array of clinically based IMRT cases. Maximization of
      cell kill was achieved by concentrating the highest doses in the middle of a
      fraction, while minimization was achieved by spreading the highest doses between
      the beginning and end. The percent difference between maximum and minimum cell
      kill (%Diff(min/max)) and the difference between maximum and minimum total doses
      normalized to 2 Gy/fx (deltaNTD(2 Gy)) was calculated for varying fraction
      durations (T), alpha/beta ratios, and doses/fx. RESULTS: %Diff(min/max) and
      deltaNTD(2 Gy) both increased with increasing T and with decreasing alpha/beta.
      The largest increases occurred with dose/fx. With alpha/beta = 3 Gy and 30
      min/fx, %Diff(min/max) ranged from 2.7-5.3% for 2 Gy/fx to 48.6-74.1% for 10
      Gy/fx, whereas deltaNTD(2 Gy) ranged from 1.2 Gy-2.4 Gy for 30 fractions of 2
      Gy/fx to 2.3-4.8 Gy for 2 fractions of 10.84 Gy/fx. Using alpha/beta = 1.5 Gy, an
      analysis of prostate hypofractionation schemes yielded differences in clinical
      outcome based on the pattern of applied dose ranging from 3.2%-6.1% of the
      treated population. CONCLUSIONS: Rearrangement of the temporal pattern of dose
      for a single IMRT fraction could be used to optimize cell kill and to directly,
      though modestly, affect treatment outcome.

PMID- 17011462
TI  - Online adaptive radiotherapy of the bladder: small bowel irradiated-volume
      reduction.
AB  - PURPOSE: To assess the potential reduction of small bowel volume receiving high
      dose radiation by using kilovoltage X-ray cone beam computed tomography (CBCT)
      and quantized margin selection for adaptive bladder cancer treatment. METHODS AND
      MATERIALS: Twenty bladder patients were planned conformally using a four-field,
      15-mm uniform margin technique. Two additional planning target volumes (PTVs)
      were created using margins quantized to 5 and 10 mm in the superior direction
      only. CBCTs (approximately 8 scans/patient) were acquired during treatment. CBCT
      volumes were registered with CT planning scans to determine setup errors and to
      select the appropriate PTV of the day. Margin reduction in other directions was
      considered. Outlining of small bowel in every fraction is required to properly
      quantify the volume of small bowel spared from high doses. In the case of CBCT
      this is not always possible owing to artifacts created by small bowel movement
      and the presence of gas. A simpler method was adopted by considering the volume
      difference between PTVs created using uniform and adapted margins, which
      corresponds to the potential volume of small bowel sparing. RESULTS: The average
      small bowel volume that can be spared by this form of adaptive radiotherapy is 31
      +/- 23 cm3 (+/-1 SD). The bladder for 1 patient was systematically smaller than
      the planning scan and hence demonstrated the largest average reduction of 76 cm3.
      The clinical target volume to PTV margins in other directions can be safely
      reduced to 10 mm except in the anterior direction where, like the superior
      direction, the bladder showed significant variation. CONCLUSIONS: Online CBCT
      assisted plan selection based on quantized margins can significantly reduce the
      volume of small bowel receiving high doses for some bladder patients. CBCT allows
      the 15-mm margins used in some directions to be safely reduced to 10 mm.

PMID- 17011464
TI  - Computer optimization of noncoplanar beam setups improves stereotactic treatment
      of liver tumors.
AB  - PURPOSE: To investigate whether computer-optimized fully noncoplanar beam setups
      may improve treatment plans for the stereotactic treatment of liver tumors.
      METHODS: An algorithm for automated beam orientation and weight selection (Cycle)
      was extended for noncoplanar stereotactic treatments. For 8 liver patients
      previously treated in our clinic using a prescription isodose of 65%, Cycle was
      used to generate noncoplanar and coplanar plans with the highest achievable
      minimum planning target volume (PTV) dose for the clinically delivered isocenter
      and mean liver doses, while not violating the clinically applied hard planning
      constraints. The clinical and the optimized coplanar and noncoplanar plans were
      compared, with respect to D(PTV,99%), the dose received by 99% of the PTV, the
      PTV generalized equivalent uniform dose (gEUD), and the compliance with the
      clinical constraints. RESULTS: For each patient, the ratio between D(PTV,99%) and
      D(isoc), and the gEUD(-5) and gEUD(-20) values of the optimized noncoplanar plan
      were higher than for the clinical plan with an average increase of respectively
      18.8% (range, 7.8-24.0%), 6.4 Gy (range, 3.4-11.8 Gy), and 10.3 Gy (range, 6.7
      12.5). D(PTV,99%)/D(isoc), gEUD(-5), and gEUD(-20) of the optimized noncoplanar
      plan was always higher than for the optimized coplanar plan with an average
      increase of, respectively, 4.5% (range, 0.2-9.7%), 2.7 Gy (range, 0.6-9.7 Gy),
      and 3.4 Gy (range, 0.6-9.9 Gy). All plans were within the imposed hard
      constraints. On average, the organs at risk were better spared with the optimized
      noncoplanar plan than with the optimized coplanar plan and the clinical plan.
      CONCLUSIONS: The use of automatically generated, fully noncoplanar beam setups
      results in plans that are favorable compared with coplanar techniques. Because of
      the automation, we found that the planning workload can be decreased from 1 to 2
      days to 1 to 2 h.

PMID- 17011465
TI  - Is there a "mucosa-sparing" benefit of IMRT for head-and-neck cancer?
AB  - PURPOSE: To investigate whether intensity-modulated radiation therapy (IMRT)
      allows more mucosal sparing than standard three-field technique (3FT)
      radiotherapy for early oropharyngeal cancer. METHODS AND MATERIALS: Whole-field
      IMRT plans were generated for 5 patients with early-stage oropharyngeal cancer
      according to Radiation Therapy Oncology Group 0022 (66 Gy/30 fractions/6 weeks)
      guidelines with and without a dose objective on the portion of mucosa not
      overlapping any PTV. 3FT plans were also generated for the same 5 patients with
      two fractionation schedules: conventional fractionation (CF) to 70 Gy/35
      fractions/7 weeks and concomitant boost (CB) to 72 Gy/40 fractions/6 weeks.
      Cumulative dose volume histograms (DVHs) of the overall mucosal volume (as per in
      house definition) from all trials were compared after transformation into the
      linear quadratic equivalent dose at 2 Gy per fraction with a time factor
      correction. RESULTS: Compared with IMRT without dose objective on the mucosa, a
      30-Gy maximum dose objective on the mucosa allows approximately 20% and
      approximately 12% mean absolute reduction in the percentage of mucosa volume
      exposed to a dose equivalent to 30 Gy (p < 0.01) and 70 Gy (p < 0.01) at 2 Gy in
      3 and 7 weeks, respectively, without detrimental effect on the coverage of other
      regions of interest. Without mucosal dose objective, IMRT is associated with a
      larger amount of mucosa exposed to clinically relevant doses compared with both
      concomitant boost and conventional fractionation; however, if a dose objective is
      placed, the reverse is true, with up to approximately 30% reduction in the volume
      of the mucosa in the high-dose region compared with both concomitant boost and
      conventional fractionation (p < 0.01). CONCLUSIONS: Intensity-modulated radiation
      therapy can be potentially provide more mucosal sparing than traditional
      approaches.

PMID- 17011466
TI  - Dosimetric verification for intensity-modulated radiotherapy of thoracic cancers
      using experimental and Monte Carlo approaches.
AB  - PURPOSE: To investigate the dosimetric accuracy of commercial treatment planning
      systems used in intensity-modulated radiotherapy (IMRT) for thoracic cancer.
      METHODS AND MATERIALS: Clinical IMRT plans for lung and esophageal cancers and
      mesothelioma were used to investigate the accuracy of dose calculations from two
      commercial treatment planning systems (Pinnacle and Corvus systems). Dose
      distributions were measured with ion chambers and thermoluminescent dosimeters
      for individual IMRT fields and composite treatment plans in water phantoms and
      anthropomorphic phantoms. A Monte Carlo-based system was established to compute
      three-dimensional dose distributions to compare with the treatment planning
      system calculations. RESULTS: Dose calculations from the Pinnacle system were
      acceptable within 5% of the local dose or a 5-mm distance-to-agreement for 80% of
      the points measured with ion chambers, 74% of the points measured with
      thermoluminescent dosimeters, and 96% of the points compared with the Monte Carlo
      calculations. For the Corvus system, 89% of the points agreed with the measured
      dose and 98% agreed with the Monte Carlo calculations. Underestimation of the
      dose from the treatment planning system was found in the low-dose regions (<50%
      of the prescribed dose), possibly caused by inadequate modeling of the multileaf
      collimators. CONCLUSION: The Pinnacle and Corvus dose calculations were
      acceptable for thoracic IMRT in high-dose regions. Beam modeling is likely the
      most critical factor for the accuracy of IMRT dose calculations.

PMID- 17011468
TI  - Brachytherapy vs. IMRT for irradiation of the vaginal vault: in regard to Aydogan
      et al. (Int J Radiat Oncol Biol Phys 2006;65:266-273).

PMID- 17011469
TI  - Introduction.

PMID- 17011470
TI  - Clinical experience with substrate reduction therapy.
AB  - The introduction of substrate reduction therapy (SRT) using miglustat
      (Zavesca(R)) gives physicians and patients a choice of treatment options for type
      1 Gaucher's disease. Enzyme replacement therapy (ERT) has proven a successful
      approach to treating the haematologic abnormalities and organomegaly. However,
      long-term complications such as skeletal disease and subtle abnormalities in the
      nervous system do not respond as well, if at all, to ERT. The basic concept
      behind ERT is acceleration of the degradation of accumulated cerebroside. In
      contrast, SRT prevents the accumulation of glucocerebroside by inhibiting the
      enzyme responsible for its synthesis. We have used the European Working Group on
      Gaucher's disease guidelines as a basis for switching patients, all of whom had
      previously been treated with ERT, to miglustat. Our initial experience with our
      cohort of six patients with type I Gaucher's disease indicates that oral
      miglustat provides an effective alternative for patients unsuitable for ERT. The
      successful use of enzyme replacement therapy over the past decade has completely
      changed the outlook for patients with Gaucher's disease in the developed world
      such that for most adults, treatment successfully improves the organomegaly and
      blood counts. However, intravenous therapy is not suitable for all patients. In
      addition, it is clear that enzyme replacement therapy does not reverse all of the
      pathology of adult Gaucher's disease. Future challenges include improving
      therapy, offering patients choice, improving our understanding of the
      pathophysiology and making treatment available worldwide.

PMID- 17011471
TI  - Epidemiology and natural history of Gaucher's disease.
AB  - Gaucher's disease was first described by Philippe Gaucher in 1882, who recognized
      that this was a systemic disease. The biochemical defect, genetic basis and
      molecular epidemiology have subsequently been characterized. Gaucher's disease
      arises as a result of a deficiency of glucocerebrosidase and is the commonest of
      the lysosomal storage disorders. The overall incidence is approximately 1:40,000
      individuals, but it is much commoner amongst individuals of Ashkenazi Jewish
      origin. A small number of genotypes are characteristically encountered amongst
      this population and the commonest of these (N370S) encodes an enzyme that has
      sufficient residual enzyme activity to ensure that significant neurologic disease
      does not occur. The main clinical features of adult Gaucher's disease are organ
      enlargement (liver and spleen), bone marrow infiltration leading to anaemia,
      thrombocytopenia and leucopenia, and skeletal involvement leading to bone pain
      and pathological fracture. There is also an association with Parkinson's disease,
      cancer and lymphoproliferative disease, illustrating that Gaucher's disease is a
      multi-system disorder with manifestations in most organ systems. The underlying
      pathophysiology is imperfectly understood, but it is increasingly clear that
      inflammation mediated by cytokines is responsible for a significant part of the
      pathology.

PMID- 17011472
TI  - The French 'observatoire' on Gaucher's disease.
AB  - Registries of patients with rare diseases are important and represent valuable
      sources of information on epidemiology, natural history of the disease, treatment
      response and medical practices. The French 'observatoire' on Gaucher's disease
      has both an epidemiological and educational objective: It will describe a large
      population of adult patients with special attention to complications and quality
      of life assessment. All adult patients with a confirmed diagnosis of Gaucher's
      disease will be enrolled at the time of their regular visit to the
      investigational centre. Collection will be as comprehensive as possible, covering
      the classical parameters of Gaucher's disease with patients' complaints, clinical
      abnormalities, imaging and biological assessments and concomitant medications.
      Special attention will be devoted to investigating the nature, frequency and
      severity of associated complications with special emphasis on neurological and
      bone involvement. Quality of life will be assessed using the SF-36 questionnaire.
      Recruitment will last for 1 year from May 2005. These large database collected
      will enhance disease knowledge and ultimately lead to improved long-term
      management of Gaucher's disease patients.

PMID- 17011473
TI  - Management of patients with Gaucher's disease: Clinical perspectives.
AB  - Gaucher's disease is a clinically heterogeneous disorder, including neuropathic
      and non-neuropathic variants. Among patients with non-neuropathic (type I
      disease), the wide variability in age of onset and the differential pattern and
      severity of disease expression complicate decision-making in relation to
      treatment. Optimal care may necessitate both palliative and adjunctive therapies.
      In the more mildly affected patient without clear signs of disease progression,
      the main issue is the appropriate time to intervene. In moderately to severely
      affected patients, the challenges include selection of an optimal treatment
      regimen and dealing with residual disease burden. Eventually, in well-controlled
      patients, guidance will be required on long-term maintenance regimens that will
      have to take the cost of care into consideration. Guidelines reached by consensus
      will hopefully reduce variation in clinical practice and promote integrated care
      pathways.

PMID- 17011474
TI  - Flaxseed.

PMID- 17011475
TI  - Lycopene.
AB  - Oxidative stress is now recognized as an important etiological factor in the
      causation of several chronic diseases including cancer, cardiovascular diseases,
      osteoporosis, and diabetes. Antioxidants play an important role in mitigating the
      damaging effects of oxidative stress on cells. Lycopene, a carotenoid
      antioxidant, has received considerable scientific interest in recent years.
      Epidemiological, tissue culture, and animal studies provide convincing evidence
      supporting the role of lycopene in the prevention of chronic diseases. Human
      intervention studies are now being conducted to validate epidemiological
      observations and to understand the mechanisms of action of lycopene in disease
      prevention. To obtain a better understanding of the role of lycopene in human
      health, this chapter reviews the most recent information pertaining to its
      chemistry, bioavailability, metabolism, role in the prevention of prostate cancer
      and cancer of other target organs, its role in cardiovascular diseases,
      osteoporosis, hypertension, and male infertility. A discussion of the most
      relevant molecular markers of cancer is also included as a guide to future
      researchers in this area. The chapter concludes by reviewing global intake levels
      of lycopene, suggested levels of intake, and future research directions.

PMID- 17011476
TI  - Food components that reduce cholesterol absorption.

PMID- 17011477
TI  - Imaging techniques for the study of food microstructure: a review.

PMID- 17011478
TI  - Electrodialysis applications in the food industry.

PMID- 17011479
TI  - Regarding "ACE Policy Committee letter".

PMID- 17011480
TI  - Sealed with a Kiz: How Plk1 ensures spindle pole integrity.
AB  - The kinase Plk1 plays multiple roles in regulating mitotic progression, including
      stabilization of spindle poles, but its substrates are largely unknown. A new
      study by Yamamoto and coworkers has identified a centrosomal protein, Kizuna
      (Kiz), as a mitotic substrate of Plk1 (Oshimori et al., 2006). Phosphorylation of
      Kiz ensures the integrity of spindle poles in the face of severe pulling forces
      exerted by the chromosome-attached spindle microtubules.

PMID- 17011481
TI  - mTORC2 Caught in a SINful Akt.
AB  - The target of rapamycin (TOR), a central controller of cell growth, is found in
      two distinct, highly conserved multiprotein complexes. Three recent papers in
      Cell (Jacinto et al., 2006), Developmental Cell (shiota et al., 2006; this
      issue), and Current Biology (Frias et al., 2006) shed light on mTOR complex 2
      (mTORC2) composition and in vivo function. An important new finding is that
      mTORC2 determines Akt/PKB substrate specificity rather than absolute activity.

PMID- 17011482
TI  - Found in translation: A new player in EMT.
AB  - Epithelial mesenchymal transition (EMT) is a complex process that involves
      changes in gene expression, cytoskeleton organization, cell adhesion, and
      extracellular matrix composition. Screening for genes mediating EMT and cancer
      metastasis, Waerner, Alacakaptan, and colleagues identified ILEI, a cytokine-like
      protein that plays an essential role in EMT, tumor growth, and late steps of
      metastasis.

PMID- 17011483
TI  - DEP domains: More than just membrane anchors.
AB  - The DEP domain is present in a number of signaling molecules, including Regulator
      of G protein Signaling (RGS) proteins, and has been implicated in membrane
      targeting. New findings in yeast, however, demonstrate a major role for a DEP
      domain in mediating the interaction of an RGS protein to the C-terminal tail of a
      GPCR, thus placing RGS in close proximity with its substrate G protein alpha
      subunit.

PMID- 17011484
TI  - PALM reading: Seeing the future of cell biology at higher resolution.
AB  - The inherent resolution limit of the light microscope has been a limiting factor
      in investigations of many fields of cell biology. A recent paper in Science by
      Betzig and coworkers describes a new method that can push the limit significantly
      lower.

PMID- 17011485
TI  - The diverse functions of microRNAs in animal development and disease.
AB  - MicroRNAs (miRNAs) control gene expression by translational inhibition and
      destabilization of mRNAs. While hundreds of miRNAs have been found, only a few
      have been studied in detail. miRNAs have been implicated in tissue morphogenesis,
      cellular processes like apoptosis, and major signaling pathways. Emerging
      evidence suggests a direct link between miRNAs and disease, and miRNA expression
      signatures are associated with various types of cancer. In addition, the gain and
      loss of miRNA target sites appears to be causal to some genetic disorders. Here,
      we discuss the current literature on the role of miRNAs in animal development and
      disease.

PMID- 17011486
TI  - Multicellular rosette formation links planar cell polarity to tissue
      morphogenesis.
AB  - Elongation of the body axis is accompanied by the assembly of a polarized
      cytoarchitecture that provides the basis for directional cell behavior. We find
      that planar polarity in the Drosophila embryo is established through a sequential
      enrichment of actin-myosin cables and adherens junction proteins in complementary
      surface domains. F-actin accumulation at AP interfaces represents the first break
      in planar symmetry and occurs independently of proper junctional protein
      distribution at DV interfaces. Polarized cells engage in a novel program of
      locally coordinated behavior to generate multicellular rosette structures that
      form and resolve in a directional fashion. Actin-myosin structures align across
      multiple cells during rosette formation, and adherens junction proteins assemble
      in a stepwise fashion during rosette resolution. Patterning genes essential for
      axis elongation selectively affect the frequency and directionality of rosette
      formation. We propose that the generation of higher-order rosette structures
      links local cell interactions to global tissue reorganization during
      morphogenesis.

PMID- 17011487
TI  - The C. elegans developmental fusogen EFF-1 mediates homotypic fusion in
      heterologous cells and in vivo.
AB  - During cell-cell fusion, two cells' plasma membranes merge, allowing the
      cytoplasms to mix and form a syncytium. Little is known about the mechanisms of
      cell fusion. Here, we asked whether eff-1, shown previously to be essential for
      fusion in Caenorhabditis elegans, acts directly in the fusion machinery. We show
      that expression of EFF-1 transmembrane protein drives fusion of heterologous
      cells into multinucleate syncytia. We obtained evidence that EFF-1-mediated
      fusion involves a hemifusion intermediate characterized by membrane mixing
      without cytoplasm mixing. Furthermore, syncytiogenesis requires EFF-1 in both
      fusing cells. To test whether this mechanism also applies in vivo, we conducted
      genetic mosaic analysis of C. elegans and found that homotypic epidermal fusion
      requires EFF-1 in both cells. Thus, although EFF-1-mediated fusion shares
      characteristics with viral and intracellular fusion, including an apparent
      hemifusion step, it differs from these reactions in the homotypic organization of
      the fusion machinery.

PMID- 17011488
TI  - The agrin/perlecan-related protein eyes shut is essential for epithelial lumen
      formation in the Drosophila retina.
AB  - The formation of epithelial lumina is a fundamental process in animal
      development. Each ommatidium of the Drosophila retina forms an epithelial lumen,
      the interrhabdomeral space, which has a critical function in vision as it
      optically isolates individual photoreceptor cells. Ommatidia containing an
      interrhabdomeral space have evolved from ancestral insect eyes that lack this
      lumen, as seen, for example, in bees. In a genetic screen, we identified eyes
      shut (eys) as a gene that is essential for the formation of matrix-filled
      interrhabdomeral space. Eys is closely related to the proteoglycans agrin and
      perlecan and secreted by photoreceptor cells into the interrhabdomeral space. The
      honeybee ortholog of eys is not expressed in photoreceptors, raising the
      possibility that recruitment of eys expression has made an important contribution
      to insect eye evolution. Our findings show that the secretion of a proteoglycan
      into the apical matrix is critical for the formation of epithelial lumina in the
      fly retina.

PMID- 17011489
TI  - Generation of robust left-right asymmetry in the mouse embryo requires a self
      enhancement and lateral-inhibition system.
AB  - The bilateral symmetry of the mouse embryo is broken by leftward fluid flow in
      the node. However, it is unclear how this directional flow is then translated
      into the robust, left side-specific Nodal gene expression that determines and
      coordinates left-right situs throughout the embryo. While manipulating Nodal and
      Lefty gene expression, we have observed phenomena that are indicative of the
      involvement of a self-enhancement and lateral-inhibition (SELI) system. We
      constructed a mathematical SELI model that not only simulates, but also predicts,
      experimental data. As predicted by the model, Nodal expression initiates even on
      the right side. These results indicate that directional flow represents an
      initial small difference between the left and right sides of the embryo, but is
      insufficient to determine embryonic situs. Nodal and Lefty are deployed as a SELI
      system required to amplify this initial bias and convert it into robust
      asymmetry.

PMID- 17011490
TI  - Lens specification is the ground state of all sensory placodes, from which FGF
      promotes olfactory identity.
AB  - The sense organs of the vertebrate head comprise structures as varied as the eye,
      inner ear, and olfactory epithelium. In the early embryo, these assorted
      structures share a common developmental origin within the preplacodal region and
      acquire specific characteristics only later. Here we demonstrate a fundamental
      similarity in placodal precursors: in the chick all are specified as lens prior
      to acquiring features of specific sensory or neurogenic placodes. Lens
      specification becomes progressively restricted in the head ectoderm, initially by
      FGF and subsequently by signals derived from migrating neural crest cells. We
      show that FGF8 from the anterior neural ridge is both necessary and sufficient to
      promote olfactory fate in adjacent ectoderm. Our results reveal that placode
      precursors share a common ground state as lens and progressive restriction allows
      the full range of placodal derivatives to form.

PMID- 17011491
TI  - Clonal analysis of mouse development reveals a polyclonal origin for yolk sac
      blood islands.
AB  - Direct clonal analysis of tissue and organ maturation in vivo is a critical step
      in the interpretation of in vitro cell precursor-progeny relationships. We have
      developed a method to analyze clonal progenitor contributions in vivo using ES
      cells stably expressing separate fluorescent proteins and placed into normal
      blastocysts to form tetrachimeras. Here we applied this method to the analysis of
      embryonic yolk sac blood islands. In most vertebrates, yolk sac blood islands are
      the initial sites of appearance of hematopoietic and endothelial cells. It has
      been proposed that these lineages arise from a common clonal progenitor, the
      hemangioblast, but this hypothesis has not been tested directly in physiological
      development in vivo. Our analysis shows that each island has contributions from
      multiple progenitors. Moreover, contribution by individual hemangioblast
      progenitors to both endothelial and hematopoietic lineages within an island, if
      it happens at all, is an infrequent event.

PMID- 17011492
TI  - Oct-3/4 dose dependently regulates specification of embryonic stem cells toward a
      cardiac lineage and early heart development.
AB  - The transcriptional mechanisms underlying lineage specification and
      differentiation of embryonic stem (ES) cells remain elusive. Oct-3/4 (POU5f1) is
      one of the earliest transcription factors expressed in the embryo. Both the
      pluripotency and the fate of ES cells depend upon a tight control of Oct-3/4
      expression. We report that transgene- or TGFbeta-induced increase in Oct-3/4 mRNA
      and protein levels in undifferentiated ES cells and at early stages of
      differentiation triggers expression of mesodermal and cardiac specific genes
      through Smad2/4. cDNA antisense- and siRNA-mediated inhibition of upregulation of
      Oct-3/4 in ES cells prevent their specification toward the mesoderm and their
      differentiation into cardiomyocytes. Similarly, Oct-3/4 siRNA injected in the
      inner cell mass of blastocysts impairs cardiogenesis in early embryos. Thus,
      quantitative Oct-3/4 expression is regulated by a morphogen, pointing to a
      pivotal and physiological function of the POU factor in mesodermal and cardiac
      commitments of ES cells and of the epiblast.

PMID- 17011493
TI  - The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and
      skeletal muscle differentiation.
AB  - MyoD regulates skeletal myogenesis. Since proteins associated with MyoD exert
      regulatory functions, their identification is expected to contribute important
      insights into the mechanisms governing gene expression in skeletal muscle. We
      have found that the RNA helicases p68/p72 are MyoD-associated proteins and that
      the noncoding RNA SRA also immunoprecipitates with MyoD. In vitro and in vivo
      experiments indicated that both p68/p72 and SRA are coactivators of MyoD. RNA
      interference toward either p68/p72 or SRA prevented proper activation of muscle
      gene expression and cell differentiation. Unexpectedly, reducing the levels of
      p68/p72 proteins impaired recruitment of the TATA binding protein TBP; RNA
      polymerase II; and the catalytic subunit of the ATPase SWI/SNF complex, Brg-1,
      and hindered chromatin remodeling. These findings reveal that p68/p72 play a
      critical role in promoting the assembly of proteins required for the formation of
      the transcription initiation complex and chromatin remodeling.

PMID- 17011494
TI  - The PLZF-like protein TRA-4 cooperates with the Gli-like transcription factor TRA
      1 to promote female development in C. elegans.
AB  - The Gli-like transcription factor TRA-1 of C. elegans promotes female development
      by repressing the transcription of male-specific genes. We have found that tra-1
      interacts with tra-4, a previously uncharacterized gene that encodes a protein
      similar to the human proto-oncoprotein and transcriptional repressor PLZF. In
      this context, the TRA-4 protein functions with NASP-1, a C. elegans homolog of
      the mammalian histone chaperone NASP, and the histone deacetylase HDA-1. We also
      found that tra-4 is a member of the synMuv B group of genes, many of which encode
      homologs of components of the Drosophila Myb-Muv B transcriptional repressor
      complex, and that several synMuv B genes also promote female development. Based
      on these results, we propose that male-specific genes are repressed in C. elegans
      hermaphrodites by the combined action of TRA-1/Gli, a complex composed of TRA
      4/PLZF-like, NASP, and HDA-1/HDAC, and synMuv B proteins. Similar interactions
      may function in sex determination and developmental regulation in other species.

PMID- 17011495
TI  - An intrinsic cell cycle checkpoint pathway mediated by MEK and ERK in Drosophila.
AB  - Cell cycle checkpoints are surveillance mechanisms that safeguard genome
      integrity. While the extrinsic pathways that halt the cell cycle in response to
      DNA damages have been well documented, the intrinsic pathways that ensure orderly
      progression of cell cycle events are not well understood. We demonstrate that
      Drosophila MEK and ERK constitute an essential intrinsic checkpoint pathway that
      restrains cell cycle progression in the absence of DNA damage and also responds
      to ionizing radiation to arrest the cell cycle. Embryos lacking MEK exhibit
      faster and extra division cycles and fail to undergo timely midblastula
      transition (MBT) or arrest following ionizing radiation. Conversely,
      constitutively activated MEK causes cell cycle arrest. Further, MEK activation in
      the early embryo is cell cycle-dependent and Raf independent and increases in
      response to ionizing radiation or in the absence of Chk1. Thus, MEK/ERK
      activation is required for multiple checkpoints and is essential for orderly cell
      cycle progression.

PMID- 17011496
TI  - The brain is getting ready for dinner.
AB  - Every evening, as we get ready for dinner, in addition to the routine behaviors
      of preparing the meal itself, we also prepare our bodies to cope with the
      upcoming meal. This could take the form of making restaurant reservations,
      changing into appropriate attire, washing hands, priming ourselves with an
      aperitif, or even consciously avoiding snacks as the meal approaches. A study by
      Johnstone and colleagues in this issue of Cell Metabolism (Johnstone et al.,
      2006) provides evidence that in parallel to our learned preparatory behaviors,
      our central nervous system is going through comparable motions as it gets ready
      for the anticipated meal.

PMID- 17011497
TI  - Regulation of ribosome biogenesis: where is TOR?
AB  - Li et al., (2006) have shown that TOR complex 1 in yeast binds directly to the
      rDNA promoter and thereby activates Pol I-dependent synthesis of 35S RNA. This is
      an important advance in the understanding of how ribosome biogenesis is regulated
      in response to environmental conditions.

PMID- 17011498
TI  - Treating obesity: does antagonism of NPY fit the bill?
AB  - In this issue of Cell Metabolism, Erondu et al., (2006) identify a selective
      neuropeptide Y5 receptor antagonist that, as predicted from rodent studies,
      results in weight loss when administered to overweight and obese human subjects.
      In a one-year randomized placebo-controlled clinical trial, the weight loss was
      modest; the results support the emerging concept that NPY acts via overlapping
      and redundant energy homeostasis pathways.

PMID- 17011499
TI  - Transcriptional control of adipocyte formation.
AB  - A detailed understanding of the processes governing adipose tissue formation will
      be instrumental in combating the obesity epidemic. Much progress has been made in
      the last two decades in defining transcriptional events controlling the
      differentiation of mesenchymal stem cells into adipocytes. A complex network of
      transcription factors and cell-cycle regulators, in concert with specific
      transcriptional coactivators and corepressors, respond to extracellular stimuli
      to activate or repress adipocyte differentiation. This review summarizes advances
      in this field, which constitute a framework for potential antiobesity strategies.

PMID- 17011501
TI  - Release of small transmitters through kiss-and-run fusion pores in rat pancreatic
      beta cells.
AB  - Exocytosis of secretory vesicles begins with a fusion pore connecting the vesicle
      lumen to the extracellular space. This pore may then expand or it may close to
      recapture the vesicle intact. The contribution of the latter, termed kiss-and
      run, to exocytosis of pancreatic beta cell large dense-core vesicles (LDCVs) is
      controversial. Examination of single vesicle fusion pores demonstrated that rat
      beta cell LDCVs can undergo exocytosis by rapid pore expansion, by the formation
      of stable pores, or via small transient kiss-and-run fusion pores. Elevation of
      cAMP shifted LDCV fusion pore openings to the transient mode. Under this
      condition, the small fusion pores were sufficient for release of ATP, stored
      within LDCVs together with insulin. Individual ATP release events occurred
      coincident with amperometric "stand alone feet" representing kiss-and-run.
      Therefore, the LDCV kiss-and-run fusion pores allow small transmitter release but
      likely retain the larger insulin peptide. This may represent a mechanism for
      selective intraislet signaling.

PMID- 17011500
TI  - Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight
      loss in overweight and obese adults.
AB  - Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonism of NPY
      Y1 and NPY Y5 receptors (NPYxR) is considered a potentially important anti
      obesity drug target. We tested the hypothesis that blockade of the NPY5R will
      lead to weight loss in humans using MK-0557, a potent, highly selective, orally
      active NPY5R antagonist. The initial series of experiments reported herein,
      including a multiple-dose positron-emission tomography study and a 12 week proof
      of concept/dose-ranging study, suggested an optimal MK-0557 dose of 1 mg/day. The
      hypothesis was then tested in a 52 week, multicenter, randomized, double-blind,
      placebo-controlled trial involving 1661 overweight and obese patients. Although
      statistically significant at 52 weeks, the magnitude of induced weight loss was
      not clinically meaningful. These observations provide the first clinical insight
      into the human NPY-energy homeostatic pathway and suggest that solely targeting
      the NPY5R in future drug development programs is unlikely to produce therapeutic
      efficacy.

PMID- 17011502
TI  - The pancreatic beta cell is a key site for mediating the effects of leptin on
      glucose homeostasis.
AB  - The hormone leptin plays a crucial role in maintenance of body weight and glucose
      homeostasis. This occurs through central and peripheral pathways, including
      regulation of insulin secretion by pancreatic beta cells. To study this further
      in mice, we disrupted the signaling domain of the leptin receptor gene in beta
      cells and hypothalamus. These mice develop obesity, fasting hyperinsulinemia,
      impaired glucose-stimulated insulin release, and glucose intolerance, similar to
      leptin receptor null mice. However, whereas complete loss of leptin function
      causes increased food intake, this tissue-specific attenuation of leptin
      signaling does not alter food intake or satiety responses to leptin. Moreover,
      unlike other obese models, these mice have reduced fasting blood glucose. These
      results indicate that leptin regulation of glucose homeostasis extends beyond
      insulin sensitivity to influence beta cell function, independent of pathways
      controlling food intake. These data suggest that defects in this adipoinsular
      axis could contribute to diabetes associated with obesity.

PMID- 17011503
TI  - Non-DNA binding, dominant-negative, human PPARgamma mutations cause
      lipodystrophic insulin resistance.
AB  - PPARgamma is essential for adipogenesis and metabolic homeostasis. We describe
      mutations in the DNA and ligand binding domains of human PPARgamma in
      lipodystrophic, severe insulin resistance. These receptor mutants lack DNA
      binding and transcriptional activity but can translocate to the nucleus, interact
      with PPARgamma coactivators and inhibit coexpressed wild-type receptor.
      Expression of PPARgamma target genes is markedly attenuated in mutation
      containing versus receptor haploinsufficent primary cells, indicating that such
      dominant-negative inhibition operates in vivo. Our observations suggest that
      these mutants restrict wild-type PPARgamma action via a non-DNA binding,
      transcriptional interference mechanism, which may involve sequestration of
      functionally limiting coactivators.

PMID- 17011504
TI  - Neuronal activation in the hypothalamus and brainstem during feeding in rats.
AB  - We trained rats to a regime of scheduled feeding, in which food was available for
      only 2 hr each day. After 10 days, rats were euthanized at defined times relative
      to food availability, and their brains were analyzed to map Fos expression in
      neuronal populations to test the hypothesis that some populations are activated
      by hunger whereas others are activated by satiety signals. Fos expression
      accompanied feeding in several hypothalamic and brainstem nuclei. Food ingestion
      was critical for Fos expression in noradrenergic and non-noradrenergic cells in
      the nucleus tractus solitarii and area postrema and in the supraoptic nucleus, as
      well as in melanocortin-containing cells of the arcuate nucleus. However,
      anticipation of food alone activated other neurons in the arcuate nucleus and in
      the lateral and ventromedial hypothalamus, including orexin neurons. Thus
      orexigenic populations are strongly and rapidly activated at the onset of food
      presentation, followed rapidly by activity in anorexigenic populations when food
      is ingested.

PMID- 17011505
TI  - Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway
      from the hindbrain to the hypothalamus.
AB  - Ghrelin, a gastrointestinal peptide, stimulates feeding when administered
      peripherally. Blockade of the vagal afferent pathway abolishes ghrelin-induced
      feeding, indicating that the vagal afferent pathway may be a route conveying
      orexigenic ghrelin signals to the brain. Here, we demonstrate that peripheral
      ghrelin signaling, which travels to the nucleus tractus solitarius (NTS) at least
      in part via the vagus nerve, increases noradrenaline (NA) in the arcuate nucleus
      of the hypothalamus, thereby stimulating feeding at least partially through alpha
      1 and beta-2 noradrenergic receptors. In addition, bilateral midbrain
      transections rostral to the NTS, or toxin-induced loss of neurons in the
      hindbrain that express dopamine beta hydroxylase (an NA synthetic enzyme),
      abolished ghrelin-induced feeding. These findings provide new evidence that the
      noradrenergic system is necessary in the central control of feeding behavior by
      peripherally administered ghrelin.

PMID- 17011506
TI  - The interaction between design and occupier behaviour in the safety of new homes.
AB  - The design of new homes includes many safety features intended to protect
      occupiers from injury or ill health within the home, however the effectiveness of
      these primary intervention measures is likely to be affected by user behaviour.
      This study examined the interaction between user activity and dwelling design and
      how this might affect health and safety. It aimed to identify how people use
      features within new homes and how this may limit the protection afforded by
      building design, codes and regulations. Forty, home-based, semi-structured, in
      depth interviews and home inspections were conducted with individuals recently
      inhabiting a new home. A range of behaviours were reported in relation to
      building features including fire doors, pipes and cables, and loft access, which
      may lead to increased risk of injury or ill-health. For example, occupiers
      described interfering with the self-closing mechanisms on fire doors and drilling
      into walls without considering the location of services. They also reported
      knowingly engaging in unsafe behaviour when accessing the loft, increasing their
      risk of falls. The accounts suggest that designers and builders need to give
      greater consideration to how occupier behaviour interacts with building features
      so that improvements in both design and occupier education can lead to improved
      health and safety.

PMID- 17011507
TI  - Formation of polyelectrolyte-surfactant complexes on surfaces.
AB  - The interfacial behavior of polyelectrolytes, mainly cationic with varying
      content of amphiphilic groups, and their complexes with oppositely charged
      surfactant are discussed. Both the kinetics and the reversibility aspect of the
      adsorption are considered. The structure of adsorbed layer formed was found to be
      dependent not only on the bulk solution phase behavior, but also on the pre
      applied conditions, i.e., the path used to obtain a particular solution condition
      (e.g., by changing pH and concentration of salt, surfactant or polymer).
      Polyelectrolyte adsorption appears only partly reversible, due to its high
      affinity to the surface, which slows down the adsorption process. In general,
      relaxation occurs more easily if the direction of the process is from low to high
      surface coverage. Association of the surfactant with the polymer, which depends
      on the surfactant concentration, can completely alter the interfacial behavior.
      Maximum adsorption occurs generally at a surfactant concentration just before the
      expected phase separation region, while the complex in some cases could desorb
      from the surface at high enough surfactant concentration (above the cmc).
      Different results were obtained for coadsorption of amphiphilic polyelectrolytes
      when surfactant was added to the preadsorbed polymer layers and when complexes
      were pre-formed in the solution prior to exposing the surface to the polymer
      surfactant solution.

PMID- 17011508
TI  - The evaluation of smaller plasterboards on productivity, work demands and
      workload in construction workers.
AB  - Manual handling of plasterboards in order to construct interior building walls is
      a risk factor for musculoskeletal complaints. Unfortunately, mechanical lifting
      aids to reduce the physical workload are impractical for this task. Therefore,
      the effect of smaller plasterboards on productivity, work demands and workload
      was evaluated in an exploratory study among experienced construction workers (n=4
      8) at the worksite. The dimensions and weight of the conventional and smaller
      plasterboards (PB) were: PB120 (2440 x 1200 x 15 mm; 33 kg) and PB90 (2440 x 900
      x 12.5 mm; 20 kg), respectively. Productivity was defined as meters of
      plasterboard mounted. Work demands were assessed by means of real time
      observations of tasks and activities. Workload was determined using continuous
      heart rate monitoring and subjective judgments of perceived workload.
      Productivity and total work time per working day did not differ between PB120 and
      PB90. Duration of mounting (29% increase) and anchoring (26% increase) were
      longer for PB90 than PB120. Duration of lifting, carrying and turning over
      plasterboards, and percentage of heart rate reserve showed no difference between
      PB120 and PB90. A majority of the workers preferred PB90. For the last two
      reasons and because PB90 weighs approximately 40% less than PB120, PB90 seems
      preferable. The workload in both conditions, however, was considered high.

PMID- 17011509
TI  - Expression of adenosine receptors in cardiac fibroblasts as a function of insulin
      and glucose level.
AB  - Adenosine among other factors is known to regulate the growth and function of
      cardiac fibroblasts (CFs). Its action is mediated by cell-surface receptors
      linked to a variety of signaling systems. The goal of present work was to examine
      the effects of glucose and insulin on adenosine receptors (ARs) mRNA and protein
      level in primary culture of rat CFs by means of real-time PCR and Western blot.
      Elevated glucose level increased the expression of A(1)-AR, A(2A)-AR, decreased
      the expression of A(3)-AR, and had no effect on A(2B)-AR expression. On the other
      hand insulin suppressed the expression of A(1)-AR, and A(2B)-AR, and had no
      effect on A(2A)-AR and A(3)-AR expression. Our measurements showed that
      accumulation of cAMP in response to ARs agonists correlated well with the changes
      in receptors expression level. These results indicate that changes in glucose and
      insulin level independently and differentially regulate the ARs expression and
      functional state in CFs.

PMID- 17011511
TI  - Formation of transmembrane ionic channels of primary amphipathic cell-penetrating
      peptides. Consequences on the mechanism of cell penetration.
AB  - The ability of three primary amphipathic Cell-Penetrating Peptides (CPPs) CH3-CO
      GALFLGFLGAAGSTMGAWSQPKKKRKV-NH-CH2-CH2-SH, CH3-CO-GALFLAFLAAALS LMGLWSQPKKKRKV-NH
      CH2-CH2-SH, and CH3-CO-KETWWETWWTEWSQPKKKRKV-NH-CH2-CH2-SH called Pbeta, Palpha
      and Pep-1, respectively, to promote pore formation is examined both in Xenopus
      oocytes and artificial planar lipid bilayers. A good correlation between pore
      formation and their structural properties, especially their conformational
      versatility, was established. This work shows that the cell-penetrating peptides
      Pbeta and Pep-1 are able to induce formation of transmembrane pores in artificial
      bilayers and that these pores are most likely at the basis of their ability to
      facilitate intracellular delivery of therapeutics. In addition, their behaviour
      provides some information concerning the positioning of the peptides with respect
      to the membrane and confirms the role of the membrane potential in the
      translocation process.

PMID- 17011512
TI  - PPARalpha agonists up-regulate organic cation transporters in rat liver cells.
AB  - It has been shown that clofibrate treatment increases the carnitine concentration
      in the liver of rats. However, the molecular mechanism is still unknown. In this
      study, we observed for the first time that treatment of rats with the peroxisome
      proliferator activated receptor (PPAR)-alpha agonist clofibrate increases hepatic
      mRNA concentrations of organic cation transporters (OCTNs)-1 and -2 which act as
      transporters of carnitine into the cell. In rat hepatoma (Fao) cells, treatment
      with WY-14,643 also increased the mRNA concentration of OCTN-2. mRNA
      concentrations of enzymes involved in carnitine biosynthesis were not altered by
      treatment with the PPARalpha agonists in livers of rats and in Fao cells. We
      conclude that PPARalpha agonists increase carnitine concentrations in livers of
      rats and cells by an increased uptake of carnitine into the cell but not by an
      increased carnitine biosynthesis.

PMID- 17011510
TI  - Oligomeric states of the SecA and SecYEG core components of the bacterial Sec
      translocon.
AB  - Many proteins synthesized in the cytoplasm ultimately function in non-cytoplasmic
      locations. In Escherichia coli, the general secretory (Sec) pathway transports
      the vast majority of these proteins. Two fundamental components of the Sec
      transport pathway are the SecYEG heterotrimeric complex that forms the channel
      through the cytoplasmic membrane, and SecA, the ATPase that drives the preprotein
      to and across the membrane. This review focuses on what is known about the
      oligomeric states of these core Sec components and how the oligomeric state might
      change during the course of the translocation of a preprotein.

PMID- 17011513
TI  - Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin
      secretion in beta-cells.
AB  - Glucose stimulation of pancreatic beta-cells is reported to lead to sustained
      alkalization, while extracellular application of weak bases is reported to
      inhibit electrical activity and decrease insulin secretion. We hypothesize that
      beta-cell K(ATP) channel activity is modulated by alkaline pH. Using the excised
      patch-clamp technique, we demonstrate a direct stimulatory action of alkali pH on
      recombinant SUR1/Kir6.2 channels due to increased open probability. Bath
      application of alkali pH similarly activates native islet beta-cell K(ATP)
      channels, leading to an inhibition of action potentials, and hyperpolarization of
      membrane potential. In situ pancreatic perfusion confirms that these cellular
      effects of alkali pH are observable at a functional level, resulting in decreases
      in both phase 1 and phase 2 glucose-stimulated insulin secretion. Our data are
      the first to report a stimulatory effect of a range of alkali pH on K(ATP)
      channel activity and link this to downstream effects on islet beta-cell function.

PMID- 17011515
TI  - Involvement of insect-derived growth factor (IDGF) in the cell growth of an
      embryonic cell line of flesh fly.
AB  - Insect-derived growth factor (IDGF) is the first adenosine deaminase-related
      growth factor (ADGF) purified from the conditioned medium of NIH-Sape-4, an
      embryonic cell line of Sarcophaga peregrina (flesh fly). Here we show the
      requirement of IDGF for the growth of NIH-Sape-4 cells. Growth factor activity
      was abolished by adsorption of IDGF from the conditioned medium of NIH-Sape-4
      cells. In addition, knockdown of IDGF gene expression by RNA interference (RNAi)
      significantly reduced IDGF secretion from the cells following cell growth
      inhibition. The IDGF gene was strongly expressed in the hemocytes, and IDGF
      increased the viability of the larval hemocytes. These data provide evidence that
      IDGF is required for the growth of NIH-Sape-4 cells and possibly for hemocyte
      viability.

PMID- 17011514
TI  - PTEN enhances TNF-induced apoptosis through modulation of nuclear factor-kappaB
      signaling pathway in human glioma cells.
AB  - The PTEN tumor suppressor gene modulates cell growth and survival known to be
      regulated by the activation of the transcription factor NFkappaB, suggesting PTEN
      might affect the NFkappaB activation pathway. We found that PTEN inhibited
      NFkappaB activation induced by TNF. The suppression of NFkappaB activation
      correlated with sequential inhibition of the tumor necrosis factor-induced
      expression of NFkappaB-regulated anti-apoptotic (IAP1, IAP2, Bcl-2, Bcl-xL,
      cFLIP, Bfl-1/A1, and survivin) gene products. Downregulation of the antiapoptotic
      genes by PTEN increased TNF-induced apoptosis, as indicated by caspase
      activation, TUNEL, annexin staining, and esterase assay. We conclude that the
      ectopic expression of PTEN enhances TNF-induced apoptosis and downregulates the
      proliferation of glioma cells through the suppression of various molecules
      including NFkappaB, and various mediators of cellular survival and proliferation,
      and that this targets might be essential for its central role in the growth and
      survival of glioma cancer cells.

PMID- 17011516
TI  - The presence of a common downstream box enables the simultaneous expression of
      multiple proteins in an E. coli extract.
AB  - In our experiments to produce different combinations of recombinant proteins in a
      cell-free protein synthesis system derived from Escherichia coli, we found that
      certain pairs of ORFs were not expressed equally. Instead, only a single DNA
      species was expressed dominantly, while the expression of the others was almost
      completely repressed. This bias during the co-expression of the DNA pairs was
      eliminated when an identical downstream box sequence was added to the 5'-ends of
      the template DNA pairs. By introducing identical nucleotide sequences of the his
      tag or the downstream box of chloramphenicol acetyltransferase (CAT-DB) in front
      of the target genes that were otherwise not expressed compatibly, both of the
      encoded proteins were produced at similar productivities. Moreover, in the
      presence of a common downstream box, multiple genes were simultaneously expressed
      in the same reaction mixture. We expect that the proposed approach will offer a
      powerful tool for the preparation of unbiased protein libraries, as well as for
      studying the structure and functions of interacting proteins.

PMID- 17011517
TI  - Possible role of light in the maintenance of EIN3/EIL1 stability in Arabidopsis
      seedlings.
AB  - To examine the mechanism of EIN3-mediated gene expression by ethylene, the
      expression patterns of ethylene-inducible genes by ethylene were monitored in Col
      0 and ethylene signaling mutants. In Col-0, the inducibility of ACC oxidase by
      ethylene in light-grown seedlings was much higher than in dark-grown seedlings.
      While the expression of ACC oxidase was highly increased by ethylene not only in
      Col-0 but in ein3-1 under light treatment, this pattern was completely abrogated
      in etiolated ein3-1 seedlings, suggesting the expression of EIN3-mediated ACC
      oxidase genes could be affected by light. To check if the level of EIN3 and EIL1
      was regulated by light, cell-free degradation assays were performed. This
      resulted in the rapid degradation of these proteins within 1h after adding dark
      grown cell extracts and this degradation was retarded by light-grown extracts.
      Here, we propose that light may act as a negative regulator in the
      destabilization of EIN3/EIL1.

PMID- 17011518
TI  - The intracellular domain of amyloid precursor protein interacts with FKBP12.
AB  - To elucidate the roles of the APP intracellular domain (AICD) in the development
      of Alzheimer's disease, a yeast two-hybrid system was used to screen for AICD
      interacting proteins. Our result revealed that FKBP12, an immunophilin with a
      peptidyl-prolyl cis-trans isomerase (PPIase) activity, may interact with AICD.
      This interaction was confirmed by coimmunoprecipitation studies. FKBP12 has been
      shown to be expressed at a higher level in areas of pathology of patients with
      neurodegenerative diseases. In addition, Pin1, a member of another PPIase family,
      has been suggested to be involved in the amyloidogenic APP processing and Abeta
      production. The interaction between FKBP12 and AICD might hint at a possible role
      FKBP12 plays, probably in a fashion similar to Pin1, in the amyloidogenesis of
      APP. We also found that the interaction was interfered, in a dose-dependent
      manner, by FK506, whose neuroprotective effect has been suggested to be
      correlated with its PPIase inhibitory activity.

PMID- 17011519
TI  - Fetuin-null mice are protected against obesity and insulin resistance associated
      with aging.
AB  - alpha2-HS glycoprotein (AHSG), also known as fetuin-A, inhibits insulin receptor
      autophosphorylation and tyrosine kinase activity in vitro and in vivo. Earlier we
      have shown that fetuin-null (KO) mice demonstrate improved insulin sensitivity
      and resistance to diet-induced obesity. Since aging is associated with insulin
      resistance and impaired glucose handling, we tested the hypothesis that fetuin
      null (KO) mice are resilient to changes in insulin sensitivity associated with
      aging. Aged (80-week-old) fetuin-null mice were leaner and demonstrated
      significantly lower body weights compared to age- and sex-matched wild-type (WT)
      littermates. Leanness in aged fetuin KO mice was accompanied by a significant
      increase in dark-onset energy expenditure, without marked alteration of
      respiratory quotient. In comparison to WT mice, fetuin KO mice demonstrated a
      lower fasting insulin resistance index, and significantly lower blood glucose and
      insulin levels, following a 4h fast. Interestingly, despite significantly
      decreased insulin levels during a glucose tolerance test, aged fetuin-null mice
      demonstrated a similar glucose excursion as WT mice, indicative of improved
      insulin sensitivity. Analysis of aldehyde-fuchsin stained pancreas from aged
      fetuin KO mice indicated no difference in islet beta-cell size or number. An
      insulin tolerance test confirmed the increased insulin sensitivity of aged fetuin
      KO mice. Further, compared to WT mice, aged fetuin-null mice demonstrated
      increased skeletal muscle and liver IR autophosphorylation and TK activity. Taken
      together, this study suggests that the absence of fetuin may contribute to the
      improvement of insulin sensitivity associated with aging.

PMID- 17011520
TI  - Generation of aberrant forms of DFF40 concurrent with caspase-3 activation during
      acute and chronic liver injury in rats.
AB  - DNA fragmentation factors (DFF) form protein complexes consisting of nuclease
      DFF40/CAD and inhibitory chaperon DFF45/ICAD. Although activated caspase-3 has
      been shown to cleave DFF complexes with the release of active DFF40 and DNA
      fragmentation, the organ-specific mechanisms of DFF turnover during liver injury
      accompanied by massive apoptosis are unclear. In this study, we investigated
      hepatic profile of DFF40-immunopositive proteins in two models of liver injury in
      rats: acute ischemia/reperfusion (I/R) and chronic alcohol administration. We
      show that DFF40-like proteins occur in intact rat liver mainly as a 52kDa
      protein. Hepatic I/R-induced caspase-3 activation and a time-dependent
      accumulation of DFF40-positive protein fragments (40 and 20kDa), most likely via
      specific caspase-3 cleavage as evidenced by in vitro digestion of intact liver
      tissue with recombinant caspase-3. In addition, immunoprecipitation with DFF40
      followed by Western blot with active caspase-3 antibody revealed the presence of
      active caspase-3 in DFF40-immunopositive 20kDa proteins. Chronic alcohol
      administration in rats also resulted in a dose-dependent fragmentation of DFF40
      proteins similar to I/R injury. Collectively, these data demonstrate that DFF40
      immunopositive proteins exist in the liver as distinct, tissue-specific molecular
      forms that may be processed by caspase-3 during both acute and chronic liver
      injury.

PMID- 17011521
TI  - Haploinsufficiency in the PPARalpha and LDL receptor genes leads to gender- and
      age-specific obesity and hyperinsulinemia.
AB  - When preparing peroxisome proliferator-activated receptor (PPAR)alpha:low-density
      lipoprotein receptor (LDLR) (-/-) double knockout mice, we unexpectedly found a
      unique gender- and age-specific obesity in the F1 generation, PPARalpha (+/
      ):LDLR (+/-), even in mice fed standard chow. Body weights of the male
      heterozygous mice increased up to about 60 g at 75 weeks of age, then decreased
      by about 30 g at 100 weeks of age. More than 95% of the heterozygous mice between
      35- and 75-week-olds were overweight. Of interest, the obese heterozygous mice
      also exhibited hyperinsulinemia correlating with moderate insulin resistance.
      Hepatic gene expression of LDLR was lower than expected in the heterozygous mice,
      particularly at 50 and 75 weeks of age. In contrast, the hepatic expression of
      PPARalpha was higher than expected in obese heterozygous mice, but decreased in
      non-obese older heterozygous mice. Modulated expression of these genes may be
      partially associated with the onset of the hyperinsulinemia.

PMID- 17011522
TI  - Altered angiogenic balance in ulcerative colitis: a key to impaired healing?
AB  - Angiogenesis is an essential component of ulcer healing since it assures delivery
      of oxygen and nutrients to the healing site. Previous studies demonstrated
      increased serum and tissue levels of vascular endothelial growth factor (VEGF,
      the most potent angiogenic growth factor) in patients with active ulcerative
      colitis (UC) and animal models of UC. However, there is no explanation why the
      healing of UC-related mucosal injury is impaired despite increased expression of
      VEGF. Expression of angiogenesis inhibitors, angiostatin and/or endostatin, in UC
      has not been determined before. We examined expression of VEGF, angiostatin, and
      endostatin in two models of experimental UC. The results revealed that in
      addition to increased VEGF, both endostatin and angiostatin levels were markedly
      (2-3-folds) increased in colonic mucosa at early stage of experimental UC. This
      is the first demonstration that colitis triggers increase in angiostatin and
      endostatin levels. The results may explain why mucosal lesions heal slowly
      despite increased VEGF levels, and may provide a novel and mechanistic insight
      into UC.

PMID- 17011523
TI  - Identification of glyburide metabolites formed by hepatic and placental
      microsomes of humans and baboons.
AB  - Glyburide (glibenclamide) is a second-generation sulfonylurea used for treatment
      of type-2 and gestational diabetes mellitus. To date, two glyburide metabolites
      have been identified in maternal urine: namely, 4-trans-hydroxycyclohexyl
      glyburide and 3-cis-hydroxycyclohexyl glyburide. The use of glyburide to treat
      gestational diabetes prompted us to investigate its metabolism by the placenta.
      The metabolism of glyburide by microsomal preparations from human and baboon
      placenta was compared with metabolism by their livers. The metabolites formed by
      the microsomes of the four tissues were identified by high-performance liquid
      chromatography-mass spectrometry using retention times, ion current (extracted at
      m/z 510), and selected-ion monitoring. The data obtained revealed the formation
      of six distinct hydroxylated derivatives of glyburide by each of the four
      microsomal preparations. However, the amounts of the six metabolites formed by
      the placentas were a fraction of that formed by the livers. Moreover, the
      relative quantities of each metabolite formed differed between species as well as
      between the two tissues. Also, the structure of the unidentified metabolites was
      determined by comparison with synthesized standards. These metabolites were
      identified as the 4-cis-hydroxycyclohexyl glyburide, 3-trans-hydroxycyclohexyl
      glyburide, and 2-trans-hydroxycyclohexyl glyburide. Therefore, one glyburide
      metabolite remains to be identified, but the data we obtained allowed us to
      suggest its structure.

PMID- 17011524
TI  - Heterodimerization and surface localization of G protein coupled receptors.
AB  - G protein coupled receptors (GPCRs) are one of the largest human gene families,
      and are targets for many important therapeutic drugs. Over the last few years,
      there has been a major paradigm shift in our understanding of how these receptors
      function. Formerly, GPCRs were thought to exist as monomers that, upon agonist
      occupation, activated a heterotrimeric G protein to alter the concentrations of
      specific second messengers. Until recently, this relatively linear cascade has
      been the standard paradigm for signaling by these molecules. However, it is now
      clear that this model is not adequate to explain many aspects of GPCR function.
      We now know that many, if not most, GPCRs form homo- and/or hetero-oligomeric
      complexes and interact directly with intracellular proteins in addition to G
      proteins. It now appears that many GPCRs may not function independently, but
      might more accurately be described as subunits of large multi-protein signaling
      complexes. These observations raise many important new questions; some of which
      include: (1) how many functionally and pharmacologically distinct receptor
      subtypes exist in vivo? (2) Which GPCRs physically associate, and in what
      stochiometries? (3) What are the roles of individual subunits in binding ligand
      and activating responses? (4) Are the pharmacological or signaling properties of
      GPCR heterodimers different from monomers? Since these receptors are the targets
      for a large number of clinically useful compounds, such information is likely to
      be of direct therapeutic importance, both in understanding how existing drugs
      work, but also in discovering novel compounds to treat disease.

PMID- 17011525
TI  - Effect of SNP at position 40237 in exon 7 of the TPH2 gene on susceptibility to
      suicide.
AB  - OBJECTIVE: The novel tryptophan hydroxylase isoform (TPH2), being the rate
      limiting enzyme in the biosynthesis of serotonin, has many biological functions
      and plays an important role as candidate gene in several psychiatric disorders.
      Here, an A-G single nucleotide polymorphism (SNP) at the position 40237 relative
      to 5'-end of TPH2 gene was selected for the association with suicide behavior.
      METHODS: The study population consisted of 102 MD patients with suicide behavior
      as attempters and 123 MD patients without suicide behavior as non-attempters. The
      TPH2 SNP was determined by sequencing on an ABI 3700 automated DNA sequencer.
      RESULTS: The A allele was significantly less frequent in attempters than in non
      attempters (p=0.0067). Individuals with the A/A genotype showed a significantly
      lower risk of suicide behavior than those with the A/G or G/G genotype (OR=0.35).
      CONCLUSIONS: Our findings suggest that the A-G polymorphism of TPH2 may confer
      susceptibility to suicide behavior in MD patients.

PMID- 17011526
TI  - Pressor effects of noradrenaline injected into the lateral septal area of
      unanesthetized rats.
AB  - The lateral septal area (LSA) is involved in central cardiovascular control. In
      the present study, we report on the cardiovascular effects of noradrenaline (NA)
      injection into the LSA of unanesthetized rats, as well as on local receptors and
      peripheral mechanisms involved in their mediation. Microinjections of NA (9, 15,
      21, 27 or 45 nmol) caused long-lasting, dose-related pressor and bradycardic
      responses in unanesthetized rats. No responses were observed when the dose of 21
      nmol of NA was microinjected into medial septal area or lateral ventricle
      suggesting a main action at the LSA. No changes were observed in arterial
      pressure and heart rate when NA was injected in the LSA of anesthetized rats. The
      effects of 21 nmol of NA were abolished by local pretreatment with 10 nmol of the
      specific alpha1-receptor antagonist WB 4101, but were not affected by
      pretreatment with 10 nmol of the specific alpha2-receptor antagonist RX 821002.
      The magnitude of pressor response to NA in the LSA was increased by i.v.
      pretreatment with the ganglion blocker pentolinium (10 mg/kg) and significantly
      reduced by i.v. pretreatment with the V1-vasopressin receptor antagonist dTyr
      (CH2)5(Me) AVP (50 microg/kg). No pressor response to NA was observed in
      hypophysectomized rats. The present observation of alpha1-adrenoceptor-mediated
      pressor responses after local injection of NA confirms earlier evidence of a LSA
      involvement in central cardiovascular control. Pretreatment with the alpha1
      adrenoceptor antagonist WB-4101 did not affect baseline blood pressure or heart
      rate suggesting no tonic involvement of septal adrenergic mechanisms suggesting a
      modulatory LSA influence on cardiovascular control. Additionally, the blockade of
      the pressor response by the i.v. pretreatment with a V1-vasopressin antagonist
      indicates that noradrenergic LSA mechanisms modulate vasopressin release.

PMID- 17011527
TI  - Effects of formaldehyde exposure on granule cell number and volume of dentate
      gyrus: a histopathological and stereological study.
AB  - The hippocampal formation is a complex region of the brain related to memory and
      learning. The purpose of the present study was to determine whether exposure of
      neonatal rats to formaldehyde (FA) had either early or delayed effects on the
      numbers of granule cells in the dentate gyrus (DG). After birth, the neonatal
      male Wistar rats were exposed throughout a 30-day period to various
      concentrations of FA: 0 (control group), 6 ppm (low concentration group) and 12
      ppm (high concentration group). This was done by placing them for 6 h/day and 5
      days per week in a glass chamber containing FA vapor. Then, five animals from
      each group were anesthetized and decapitated on postnatal day (PND) 30, and the
      remaining five animals were sacrificed on PND 90 by intracardiac perfusion using
      10% neutral buffered FA solution. The Cavalieri principle of stereological
      approaches was used to determine the volume of the DG in these sections. The
      optical fractionator counting method was used to estimate the total number of
      granule cells in the DG. The appearance of granule cells was normal under light
      microscopy in all PND 30 and PND 90 groups. There were significant age-related
      reductions in the volume of the DG at PND 90 irrespective of which group was
      examined. Significant age-related neuron loss was also determined at PND 90
      compared to that at PND 30. Rats treated with a high concentration FA were found
      to have fewer granule cells than either the animals treated with a low
      concentration FA or the control group (p<0.01 and p<0.01, respectively) at PND 90
      but not at PND 30. These findings clearly indicate that granule cells in the DG
      may be vulnerable to stress and the concentration of FA to which they are exposed
      during early postnatal life, and also that a neurotoxic effect of high dose FA on
      cell number is only seen after a long time period. These results may explain why
      some disorders do not appear until later life.

PMID- 17011528
TI  - Task-related modulation in the monkey inferotemporal cortex.
AB  - The latencies of the neuronal responses from the inferotemporal cortical cells
      were analyzed in animals performing a visual fixation task and a recognition task
      with the same stimulus set. A consistent reduction in response latencies of about
      10 ms was observed in favor of the recognition task. It was found that behavioral
      relevance reduces the latency in the inferotemporal cortex and it was concluded
      that behavioral significance accelerates information processing. This effect has
      not been described previously.

PMID- 17011529
TI  - The temporal signatures of semantic and phonological activations for Chinese
      sublexical processing: an event-related potential study.
AB  - A large number of Chinese characters are made up by pairing a semantic radical
      and a phonetic radical. The phonetic radical usually gives a phonological clue
      for the pronunciation of the whole character but does not contribute to its
      meaning. Using an event-related potential (ERP) measurement, the present study
      was able to trace the very intricate interplay between phonological and semantic
      information embedded in the phonetic radical. It was found that, within the first
      50 to 100 ms of perceiving the character, the semantic information of the
      phonetic radical was better preserved when the constituent phonetic radical
      provided a valid phonological clue (e.g., regular phonogram) than when it
      contained an invalid phonetic cue (e.g., irregular phonogram). However, no trace
      of semantic information from the phonetic radical was preserved after 300 ms.
      These ERP results detail the neuropsychological steps in reading Chinese and
      support the framework of the lexical constituent model.

PMID- 17011530
TI  - Transfer of accelerated presbycusis by transplantation of bone marrow cells from
      senescence-accelerated mice.
AB  - Until now, there has been no effective therapy for chronic sensorineural hearing
      impairment. This study investigated the role of bone marrow cells (BMCs) in
      cochlear dysfunction. BALB/c mice (2 months of age), a non-presbycusis-prone
      mouse strain, were lethally irradiated and then transplanted with BMCs from SAMP1
      mice (2 months of age), a presbycusis-prone mouse strain. Acceleration of age
      related hearing loss, early degeneration of spiral ganglion cells (SGCs) and
      impairment of immune function were observed in the recipient mice as well as in
      the SAMP1 mice. However, no spiral ganglion cells of donor (SAMP1) origin were
      detected in the recipient mice. These results indicated that accelerated
      presbycusis, cochlear pathology, and immune dysfunction of SAMP1 mice can be
      transferred to BALB/c recipient mice using allogeneic bone marrow transplantation
      (BMT). However, although the BMCs themselves cannot differentiate into the spiral
      ganglion cells (SGCs), they indirectly cause the degeneration of the SGCs.
      Further studies into the relationship between the inner ear cells and BMCs are
      required.

PMID- 17011531
TI  - Cognitive effects of SL65.0155, a serotonin 5-HT4 receptor partial agonist, in
      animal models of amnesia.
AB  - Given that several data suggest the involvement of serotonergic (5-HT) system,
      particularly the serotonin 5-HT(4) receptors, in memory processes; this study was
      undertaken to investigate the role of serotonin 5-HT(4) receptors in different
      experimental models of amnesia in male Swiss mice or in male Sprague-Dawley rats,
      tested in learning and memory tasks. Amnesia was induced in mice by
      intracerebroventricular (i.c.v.) injection of beta-amyloid 1-42 fragment (BAP 1
      42; 400 pmol/mouse) or of galanin (GAL) 1-29 (3 microg/mouse). Another group of
      animals was exposed to carbon monoxide (CO). Treatments were made 14 days, 15 min
      or 8 days prior to the learning trial of a step-through passive avoidance
      paradigm, respectively. Latency to re-enter the dark box appeared to be reduced
      in all treatment groups. Intraperitoneal (i.p.) administration of SL65.0155 (5-(8
      amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-[1-(2-phenylethyl)-4
      piperidinyl]-1,3,4-oxadiazol-2(3H)-one-monohydrochloride), a serotonin 5-HT(4)
      receptor partial agonist (1 mg/kg/day), for 7 days prior to the learning trial,
      inhibited the amnesic effect of both peptides increasing the latency to re-enter
      the dark box also in mice exposed to CO. In rats with ibotenate-induced lesions
      of the nucleus basalis magnocellularis (NBM) or prenatally exposed to
      methylazoxymethanol (MAM), SL65.0155 (1 mg/kg/day, i.p.) administered for 7 days,
      improved the learning and memory capacity in animals tested in shuttle-box active
      avoidance and radial maze tests. These findings give further support to the
      hypothesis of SL65.0155 cognition-enhancing activity across a range of tasks.

PMID- 17011532
TI  - Dithranol abolishes UCH-L1 immunoreactivity in the nerve fibers of the rat
      orofacial skin.
AB  - Dithranol has been used to treat psoriasis for decades. Although its beneficial
      effect may involve the induction of cutaneous inflammation, and inflammation
      often leads to damages in nerve fibers, these alterations are not well
      documented. Therefore, we investigated the effects of dithranol on the
      immunohistochemical characteristics of the cutaneous nerve fibers in the rat
      skin. Epidermal nerve fiber staining was achieved with ubiquitin carboxyl
      terminal hydrolase L1 (UCH-L1) immunohistochemistry in the orofacial skin of
      control rats, rats treated with (a) dithranol for 5 days, (b) corticosteroid for
      5 days following dithranol treatment for 5 days, and (c) corticosteroid for 5
      days. The results revealed a complete loss of UCH-L1 immunoreactivity in the
      dithranol-treated animals. Topical application of corticosteroid onto the
      inflamed skin for 5 days reversed this effect: the UCH-L1 immunoreactivity was
      almost completely restored. Steroid treatment for 5 days did not change the
      appearance of the UCH-L1-immunoreactive nerve fibers. These findings were
      supported by Western blot analyses. We conclude that dithranol, incidentally
      similarly to psoriasis, causes inflammation and abolishes UCH-L1 immunoreactivity
      in the rat orofacial skin in a corticosteroid-reversible manner. This phenomenon
      may be due to the ability of dithranol to cause oxidative damage to the UCH-L1
      protein, and to the antioxidant activity of the corticosteroids countering this
      effect.

PMID- 17011533
TI  - 4-O-Acetyl-3-O-tert-butyldimethylsilyl-L-rhamnal: a building block in the
      stereoselective synthesis of 2-deoxy-alpha-L-rhamnopyranosides.
AB  - The stereoselective synthesis of 2-deoxy-alpha-L-glycosides by addition of
      various acceptors to 4-O-acetyl-3-O-tert-butyldimethylsilyl-L-rhamnal promoted by
      triphenylphosphine-hydrogen bromide is developed.

PMID- 17011534
TI  - Spatial and temporal trend evaluation of ambient concentrations of 1,3-butadiene
      and chloroprene in Texas.
AB  - This paper provides information on 1,3-butadiene (BD) and chloroprene as
      atmospheric pollutants in Texas and reviews available emission estimates and
      monitoring data. Ambient BD concentrations in most areas of Texas are
      predominantly influenced by on-road and off-road vehicular emissions or biomass
      burning, since BD is a product of combustion. However, large industrial point
      sources of BD emissions in Texas locally influence ambient concentrations. Total
      industrial BD emissions to the atmosphere in Texas for 2003 were estimated at 695
      tonnes per year (TPY), approximately 70% of the total reported national
      industrial BD air emissions. Since 1998, there have not been any large industrial
      sources of chloroprene emissions in Texas, and total industrial chloroprene
      emissions for 2003 was estimated at only 0.09 TPY. Chloroprene was never detected
      at air monitoring sites. In 2003, the Texas Commission on Environmental Quality
      (TCEQ) monitored BD ambient air concentrations at 57 sites, some of which have
      been operational since 1992. These air monitors provide information on ambient BD
      concentrations in Texas and allow spatial and temporal trend evaluation. In 2003,
      annual average concentrations at monitoring sites in Texas ranged from less than
      the reporting limit of 0.01 to 3.2 parts per billion by volume (ppbv) with an
      overall average of 0.2 ppbv. This overall average is reduced to 0.1 ppbv if BD
      data from monitoring sites in Port Neches and Milby Park in Houston, which are
      located downwind of significant point sources of BD, are excluded. Ambient air
      monitoring has been conducted in Port Neches and in Milby Park in Houston since
      1996 and 1999, respectively. At the Port Neches monitor, trend evaluation
      indicates that ambient concentrations of BD have declined since 1996 due to
      cooperative agreements with industries emitting BD. Annual average BD
      concentrations at the Port Neches monitor decreased from 8.3ppbv in 1996 to 1.3
      ppbv in 2003, giving an 8-year average of 3.8 ppbv. Annual average BD
      concentrations at the Milby Park monitor varied between 2.1 and 4.4 ppbv from
      1999 through 2003, giving a 5-year average of 3.1 ppbv. The results of cancer
      cluster studies based on Cancer Registry 1995-2001 incidence data and 1993-2002
      mortality data conducted by the Texas Department of State Health Services for zip
      codes 77017/77012 (Houston) and 77651 (Port Neches) will be presented.

PMID- 17011535
TI  - Comparison of standardized mortality ratios (SMRs) obtained from use of reference
      populations based on a company-wide registry cohort to SMRs calculated against
      local and national rates.
AB  - The DuPont Company has maintained a mortality registry for all active and
      pensioned U.S. employees since 1957. Standardized mortality ratios (SMRs) for
      each plant site in the U.S. can be calculated based on the comparison with the
      entire U.S. DuPont population or with a regional subset of DuPont employees. We
      compared the SMRs derived from a large, international cohort mortality study of
      chloroprene workers (IISRP study) with those derived from the entire DuPont
      Registry and appropriate subpopulations of the registry for two U.S. neoprene
      plants--Louisville (Kentucky) and Pontchartrain (Louisiana). SMRs from the IISRP
      study for the Louisville cohort based on national rates for all causes of death,
      all cancers, respiratory cancer, and liver cancer are higher than those based on
      local mortality rates. Both the national and local comparisons (several counties
      surrounding each plant) for all-cancer SMRs are lower than 1.0, the local
      comparison being statistically significantly reduced. In contrast, the SMRs based
      on the total U.S. DuPont worker mortality rates for all causes of death (1.13),
      all cancers (1.11), and respiratory cancers (1.37) are statistically
      significantly increased. The SMR for liver cancer (1.27), although elevated, is
      not statistically significant. SMRs based on DuPont Region 1 were closer to 1.0,
      and the SMR for all cancers was no longer significant. Stratification of the
      Louisville subcohort of males using the same cumulative exposure categories used
      in the IISRP study yielded SMRs calculated against DuPont Region 1 that were
      generally higher than those calculated against U.S. and local rates. Only the
      third exposure category showed SMRs statistically significantly above 1.0 for all
      cancers and for cancer of bronchus, trachea, and lung. However, there does not
      appear to be an exposure-response trend. The SMRs from the IISRP study for the
      Pontchartrain cohort based on national rates are higher than those based on local
      rates for all causes of death, but all are less than 1.0. The all-cause SMRs for
      both local and national comparisons are significantly reduced. There were no
      deaths from liver cancers observed in this cohort. Comparisons of the
      Pontchartrain cohort against the total U.S. DuPont worker mortality rates
      resulted in higher SMRs for all causes of death (0.98), all cancers (1.03), and
      respiratory cancer (1.08), but none were statistically significant. SMRs based on
      DuPont Region 2 showed very little change from those based on the total registry.
      The use of reference rates based on regional workers in the same large company
      produces SMRs lower than those based on the entire company population (regional
      socio-cultural effects) but higher than those based on geographically closer
      local general populations (healthy worker effect). The healthy worker effect is
      seen in cancer mortality rates as well as in other chronic diseases.

PMID- 17011536
TI  - In vitro induction of micronuclei by monofunctional methanesulphonic acid esters:
      possible role of alkylation mechanisms.
AB  - Six monofunctional alkylating methanesulphonates of widely varying structures
      were investigated in the in vitro micronucleus assay with Syrian hamster embryo
      fibroblast cells. The results were compared with the alkylating activities
      measured in the 4-(nitrobenzyl)pyridine test (NBP-test) and the N-methyl
      mercaptoimidazole (MMI-test) as measures for S(N)2 reactivity as well as in the
      triflouoroacetic acid (TFA) solvolysis and the hydrolysis reaction as measures
      for S(N)1 reactivity in order to provide insights into the role of alkylation
      mechanisms on induction of micronuclei. Moreover we compared the results of
      micronucleus assay with those of the Ames tests in strain TA 100 and TA1535 and
      with those of the SOS chromotest with the strains PQ37, PQ243, PM21 and GC 4798.
      The potency of methanesulphonates to induce micronuclei depended only to a
      certain degree, on the total alkylating activity (S(N)1 and S(N)2 reactivity). An
      inverse, significant correlation between the Ames test and the micronucleus assay
      was observed and an inverse correlation between the micronucleus assay and the
      SOS chromotest with the different strains. The results indicate that the primary
      mechanism leading to induction of micronuclei is not O-alkylation in DNA as it is
      the case in the Ames test with the hisG46 strains TA1535 and TA100 and not N
      alkylation as with the SOS chromotest. There is evidence that protein alkylation,
      e.g. in the spindle apparatus in mitosis is decisive for induction of micronuclei
      by alkylating compounds. The structurally voluminous methanesulphonates 2-phenyl
      ethyl methanesulphonate and 1-phenyl-2-propyl methanesulphonate show a clear
      higher micronuclei inducing potency than the other tested though the bulky
      methanesulphonates possess a lower total alkylating activity than the others.
      This effect can be explained by a higher disturbance during mitosis after
      alkylation of the spindle apparatus with the structurally more bulky
      methanesulphonates.

PMID- 17011537
TI  - Inhibition of cytosolic glutathione S-transferase activity from rat liver by
      copper.
AB  - H(2)O(2) inactivation of particular GST isoforms has been reported, with no
      information regarding the overall effect of other ROS on cytosolic GST activity.
      The present work describes the inactivation of total cytosolic GST activity from
      liver rats by the oxygen radical-generating system Cu(2+)/ascorbate. We have
      previously shown that this system may change some enzymatic activities of thiol
      proteins through two mechanisms: ROS-induced oxidation and non-specific Cu(2+)
      binding to protein thiol groups. In the present study, we show that nanomolar
      Cu(2+) in the absence of ascorbate did not modify total cytosolic GST activity;
      the same concentrations of Cu(2+) in the presence of ascorbate, however,
      inhibited this activity. Micromolar Cu(2+) in either the absence or presence of
      ascorbate inhibited cytosolic GST activity. Kinetic studies show that GSH but no
      1-chloro-2,4-dinitrobenzene prevent the inhibition on cytosolic GST induced by
      micromolar Cu(2+) either in the absence or presence of ascorbate. On the other
      hand, NEM and mersalyl acid, both thiol-alkylating agents, inhibited GST activity
      with differential reactivity in a dose-dependent manner. Taken together, these
      results suggest that an inhibitory Cu(2+)-binding effect is likely to be
      negligible on the overall inhibition of cytosolic GST activity observed by the
      Cu(2+)/ascorbate system. We discuss how modification of GST-thiol groups is
      related to the inhibition of cytosolic GST activity.

PMID- 17011538
TI  - A multi-marker approach for the prediction of adverse events in patients with
      acute coronary syndromes.
AB  - BACKGROUND: Cardiac troponin T (cTnT), high sensitivity C-reactive protein (hs
      CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have emerged as
      strong predictors of adverse events among patients presenting with acute coronary
      syndromes (ACS). We evaluated the prognostic performance of each of these
      markers, individually, and in combination in patients presenting to the emergency
      department (ED) with ACS symptoms. METHODS: Serum samples were obtained from 422
      consenting patients presenting to the ED with symptoms of acute coronary syndrome
      (ACS) and subsequently tested for cTnT, NT-proBNP, myoglobin, CK-MB, and hs-CRP.
      Adverse events (AEs) occurring within 30 days (death, myocardial infarction,
      unstable angina and the need for revascularization procedures) were recorded and
      ROC curves were constructed. RESULTS: AEs occurred in 42 patients (10%). Relative
      risk, cut-off, and predictive values for each biomarker were determined
      statistically, with the exception of cTnT, where the concentration meeting the
      99th percentile of a healthy population with a 10% coefficient of variation (0.03
      ng/ml) was used. These cut-off values, sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), and relative risk (RR)
      were calculated. Sensitivity and RR for a panel of cTnT and NT-proBNP were 78.6%
      (66.2-91.0) and 4.7 (2.3-9.5), respectively. CONCLUSIONS: If used alone, cTnT
      appeared to have greater prognostic value when compared to hs-CRP, NT-proBNP,
      myoglobin or CK-MB. The combination of cTnT and NT-proBNP performed better than
      the combination of cTnT and hs-CRP. When cTnT, NT-proBNP and hs-CRP were used as
      a panel, there was no significant improvement in prognostic performance over
      using cTnT and NT-proBNP together. Thus, in patients with suspected ACS, the
      measurement of both cTnT and NT-proBNP may have enhanced prognostic performance
      over using either marker in isolation.

PMID- 17011539
TI  - Intrinsic function of S100A8/A9 complex as an anti-inflammatory protein in liver
      injury induced by lipopolysaccharide in rats.
AB  - BACKGROUND: We hypothesized that the S100A8/A9 complex is effective in the
      suppression of acute inflammatory changes. METHODS: To clarify such a functional
      role of the S100A8/A9 complex in acute inflammatory disorder, the complex
      purified from human leukocytes (approx. 1 mg) was intraperitoneally injected into
      rats 1.0 or 3.5 h after an injection of lipopolysaccharide (LPS). RESULTS: The
      serum concentrations of interleukin-6 (IL-6) and nitric oxide (NOx) were
      significantly decreased in the treated rats. Conversely, when anti-S100A8/A9
      complex IgG was injected into the tail blood vessel of a rat 1.0 h after the
      injection of LPS, the serum concentration of IL-6 increased slightly, indicating
      that the antibody immunoregulatorily blocked the activity of the complex as an
      anti-inflammatory protein in vivo. In addition, the S100A8/A9 complex bound non
      specifically with interleukin-1beta (IL-1beta), IL-6 and TNF-alpha in vitro,
      suggesting that the complex could bind with these cytokines in vivo. A large
      number of endogenous S100A8/A9 complex-positive cells that accumulated in the
      inflamed region in the liver 6 h after the injection of LPS were microscopically
      observed, while apparent inflammatory changes were not found microscopically in
      other organs, such as the kidney, lung and spleen. In rats treated with the
      S100A8/A9 complex, neither acute inflammatory changes nor S100A8/A9 complex
      positive cells were also observed microscopically in the liver tissue.
      CONCLUSIONS: These findings suggest that the S100A8/A9 complex indirectly
      suppresses the overproduction of NOx from activated neutrophils and/or
      macrophages by neutralizing the activity of pro-inflammatory cytokines. Thus, the
      S100A8/A9 complex may play an important role in the suppression of acute
      inflammation by modulating the vital activity of pro-inflammatory cytokines in
      vivo.

PMID- 17011540
TI  - Concordance between the deduced acetylation status generated by high-speed: real
      time PCR based NAT2 genotyping of seven single nucleotide polymorphisms and human
      NAT2 phenotypes determined by a caffeine assay.
AB  - BACKGROUND: The utility of typing single nucleotide polymorphisms (SNPs) for the
      determination of the N-acetyltransferase 2 (NAT2) acetylation status is a matter
      of debate. AIMS OF THE STUDY: Evaluation of the concordance between deduced
      genotype results of seven human NAT2 SNPs generated by Real-time PCR analysis and
      human NAT2 phenotypes. METHODS: NAT2 phenotypes of 38 Caucasian workers were
      determined using a suitable caffeine test method. Genomic DNA aliquots were used
      for the determination of seven human NAT2-specific SNPs (G191A, C282T, T341C,
      C481T, G590A, A803G, G857A). RESULTS AND CONCLUSIONS: Phenotypic results based on
      the molar ratio of 5-acetylamino-6-formylamino-3-methyluracil (AFMU)/(AFMU+1
      methlyuric acid (1U)+1-methylxanthine (1X)) calculated from excreted caffeine
      metabolite levels in urine samples with 0.3 as a cut-off point between slow
      (<0.3) and rapid acetylators (>or=0.3). Twenty-seven samples belonged to the slow
      (mean 0.13; range: 0.03-0.25), 11 to the rapid (mean: 0.41; range: 0.34-0.48)
      acetylators. LightCycler analyses revealed 11 different NAT2 variant
      combinations, whereby *5B/*5B and *5B/*6A or *5A/*6C (each 21%), were the most
      frequent. The deduced acetylation status of the seven NAT2 SNPs matched perfectly
      with the 38 results determined by phenotyping. This study showed a 100%
      concordance between NAT2 phenotypes and the deduced NAT2 genotypes and the
      suitability of the high-speed NAT2-specific LightCycler analysis in a Caucasian
      population.

PMID- 17011541
TI  - Determination of everolimus in whole blood using the Abbott IMx sirolimus
      microparticle enzyme immunoassay.
AB  - OBJECTIVES: Everolimus (Certican) is a new immunosuppressant derived from
      sirolimus (Rapamune) with a 2-hydroxyethyl chain at position 40 of the macrolide
      ring. The aim of our study was to evaluate the possible determination of
      everolimus in whole blood using a commercialized microparticle enzyme immunoassay
      for sirolimus determination. DESIGN AND METHODS: Everolimus concentrations were
      determined in blood samples from 11 kidney transplant patients (n=51) and
      different control materials (n=35) using the Seradyn Innofluor Certican
      fluorescence polarization immunoassay (FPIA) and the Abbott IMx sirolimus
      microparticle enzyme immunoassay (MEIA). RESULTS: The MEIA gave a concentration
      dependent cross-reactivity with the everolimus, with a linear regression between
      the assigned values (y) for the Innofluor Certican calibrators and those obtained
      (x) using this immunoassay: y=0.96x+0.67 (ma68=0.21 microg/L, r=0.974, p<0.001).
      The within- and between-run coefficients of variation using the MEIA were
      <or=7.3%. In analyzing the different blood samples from patients and control
      materials using the MEIA and FPIA, a linear regression was found: MEIA=0.99FPIA
      0.46 (ma68=0.32 microg/L, r=0.967, p<0.001). Correcting the MEIA results by means
      of the linear regression equation found between the assigned values for the
      Innofluor Certican calibrators and those obtained using this immunoassay led to a
      reduction in the deviation with respect to the FPIA values. The possible effect
      of the hematocrit on the results is analogous for both immunoassays. CONCLUSIONS:
      The Abbott IMx sirolimus MEIA permits the simple and precise determination of
      everolimus in whole blood, making it a valid alternative for the therapeutic
      monitoring of this immunosuppressant agent.

PMID- 17011542
TI  - Wavelet transform analysis predicts outcome of DC cardioversion for atrial
      fibrillation patients.
AB  - The aim of this study was to examine whether wavelet transform analysis of the
      electrocardiogram (ECG) can improve the prediction of the maintenance of sinus
      rhythm in patients with atrial fibrillation (AF) after external DC cardioversion.
      We examined a variety of wavelet transform-based statistical markers as potential
      candidates for the prediction of patient status post-cardioversion. Considering a
      'success' as a patient who remains in normal sinus rhythm for one month post
      cardioversion and 'failure' as a patient who does not, it was shown the proposed
      non-parametric classification system can achieve 89% specificity at 100%
      sensitivity using a non-parametric classification method.

PMID- 17011543
TI  - Odd-skipped genes encode repressors that control kidney development.
AB  - Odd-skipped family of proteins (Odd in Drosophila and Osr in vertebrates) are
      evolutionarily conserved zinc finger transcription factors. Two Osr genes are
      present in mammalian genomes, and it was recently reported that Osr1, but not
      Osr2, is required for murine kidney development. Here, we show that in Xenopus
      and zebrafish both Osr1 and Osr2 are necessary and sufficient for the development
      of the pronephros. Osr genes are expressed in early prospective pronephric
      territories, and morphants for either of the two genes show severely impaired
      kidney development. Conversely, overexpression of Osr genes promotes formation of
      ectopic kidney tissue. Molecularly, Osr proteins function as transcriptional
      repressors during kidney formation. We also show that Drosophila Odd induces
      kidney tissue in Xenopus. This might be accomplished through recruitment of
      Groucho-like co-repressors. Odd genes may also be required for proper development
      of the Malpighian tubules, the Drosophila renal organs. Our results highlight the
      evolutionary conserved involvement of Odd-skipped transcription factors in the
      development of kidneys.

PMID- 17011544
TI  - Brn3a and Klf7 cooperate to control TrkA expression in sensory neurons.
AB  - The zinc finger protein Klf7 and POU homeodomain protein Brn3a are each required
      for efficient transcription of TrkA in primary sensory neurons. In this study, we
      examined whether these transcription factors act in concert to regulate TrkA
      expression. In vitro, Brn3a and Klf7 can synergistically activate the TrkA
      enhancer. In vivo, precursor cells that are destined to become TrkA(+) neurons
      are born. However, both Brn3a and Klf7 are dispensable for the initiation of TrkA
      expression. At E12.5, while TrkA expression is unaffected in Brn3a-/- trigeminal
      ganglia and only slightly decreased in Klf7-/- trigeminal ganglia, it is severely
      reduced in the double mutant Brn3a-/-;Klf7-/- trigeminal ganglia. At birth, all
      Trk(+) neurons are lost in Brn3a-/-;Klf7-/- trigeminal ganglia. We further
      demonstrate that the TrkA enhancer is inactive in Brn3a-/-;Klf7-/- trigeminal
      ganglia. Thus, cooperation between these two transcription factors is required
      for endogenous TrkA gene expression and the survival of nociceptive sensory
      neurons.

PMID- 17011545
TI  - Contrasting reactive oxygen species and transition metal concentrations in
      combustion aerosols.
AB  - The presence of reactive oxygen species (ROS) and 10 transition metals (Ag, Cd,
      Co, Cu, Fe, Mn, Ni, Ti, V and Zn) in both the acid-soluble and water-soluble
      fractions of fine particles of combustion origin were determined. ROS was
      analyzed using the dichlorofluorescin fluorescence technique. Particles emitted
      from on-road vehicles, gas cooking, incense burning, and cigarette smoke were
      characterized along with those in the background air of outdoor and indoor
      environments. In addition, this study evaluated the possible relationships
      between ROS and individual transition metals. It is found that cigarette smoke
      which had the highest concentration of metals also contained the highest
      concentration of ROS. Regression analysis performed showed that water-soluble
      metals including Cd, Co, Cu, Fe, Mn, and Ni showed better correlation with ROS
      concentration as compared to acid-soluble (total) metals. The findings
      demonstrated that water-soluble metals could be one of the species influencing
      ROS formation in ambient air.

PMID- 17011546
TI  - Adolescents differ from adults in cocaine conditioned place preference and
      cocaine-induced dopamine in the nucleus accumbens septi.
AB  - In humans, adolescent exposure to illicit drugs predicts the onset of adult drug
      abuse and suggests that early drug use potentiates vulnerability to drug
      addiction. Cocaine conditioned place preferences were measured in early
      adolescent [postnatal day (PND) 35], late adolescent (PND 45) and young adult
      (PND 60) rats by injecting either 0, 5 or 20 mg/kg cocaine and conditioning them
      to environmental cues. Cocaine preferences were found for all ages at the high
      dose. PND 35s were the only age group to have a preference at the low dose. To
      address whether age-related differences in cocaine place preferences were related
      to differences in the mesolimbic dopaminergic system, we measured extracellular
      dopamine levels in the nucleus accumbens septi of PND 35, PND 45 and PND 60 rats
      via quantitative microdialysis under transient conditions. Rats were injected
      daily with either 5 mg/kg/ip or saline for 4 days and surgically implanted with a
      microdialysis probe aimed at the nucleus accumbens. Rats were perfused with
      either 0, 1, 10 or 40 nM dopamine and the extracellular dopamine concentration
      was measured. Our results show that adolescents differ from adults in basal
      dopamine. All cocaine treated rats, regardless of age, showed a significant
      increase in dopamine over baseline in response to a cocaine challenge.
      Additionally, there were age-related differences in the extraction fraction
      (E(d)), an indirect measure of dopamine reuptake. Together these findings suggest
      ontogenetic differences in extracellular dopamine and dopamine reuptake and that
      these differences may provide an explanation for adolescent vulnerability to
      addiction.

PMID- 17011547
TI  - Anxiolytic effect of agmatine in rats and mice.
AB  - In mammalian brain, agmatine is an endogenous neurotransmitter and/or
      neuromodulator. In this study, the anxiolytic action of agmatine (p.o. or s.c.)
      was evaluated in three animal behavioral models in mice or rats. In the light
      dark transition test, agmatine in a single dose (80 mg/kg, s.c) or repeated
      administration (20 mg/kg, s.c. or 10 mg/kg, p.o., once a day for 3 days)
      significantly increased the number of light-dark transitions in mice.
      Furthermore, treatment with agmatine (20-80 mg/kg, s.c or 10-40 mg/kg, p.o) three
      times in 24 h significantly increased the number of licks in the Vogel's drinking
      conflict test in rats. In the social interaction test, agmatine (10-40 mg/kg,
      p.o, three times in 24 h prior to test) increased the active social interaction
      of rats. All these results indicate that agmatine exerts a significant anxiolytic
      effect in both rats and mice.

PMID- 17011548
TI  - Impaired nuclear import of mammalian Dlx4 proteins as a consequence of rapid
      sequence divergence.
AB  - Dlx genes encode a developmentally important family of transcription factors with
      a variety of functions and sites of action during vertebrate embryogenesis. The
      murine Dlx4 gene is an enigmatic member of the family; little is known about the
      normal developmental function(s) of Dlx4. Here, we show that Dlx4 is expressed in
      the murine placenta and in a trophoblast cell line where the protein localizes to
      both the nucleus and cytoplasm. Despite the presence of several leucine/valine
      rich motifs that match known nuclear export sequences, cytoplasmic Dlx4 is not
      due to CRM-1-mediated nuclear export. Rather, nuclear import of Dlx4 is
      compromised by specific residues that flank the nuclear localization signal. One
      of these residues represents a novel conserved feature of the Dlx4 protein in
      placental mammals, and the second represents novel variation within mouse Dlx4
      isoforms. Comparison of orthologous protein sequences reveals a particularly high
      rate of non-synonymous change in the coding regions of mammalian Dlx4 genes.
      Since impaired nuclear localization is unlikely to enhance the function of a
      nuclear transcription factor, these data point to reduced selection pressure as
      the basis for the rapid divergence of the Dlx4 gene within the mammalian clade.

PMID- 17011549
TI  - Unraveling androgen receptor interactomes by an array-based method: discovery of
      proto-oncoprotein c-Rel as a negative regulator of androgen receptor.
AB  - The androgen receptor (AR) plays a key role in the development and function of
      male reproductive organs. Using a high-throughput transcription factor
      transcription factor (TF-TF) interaction array method, we captured the AR
      interactomes in androgen-responsive LNCaP cells. Several known and unknown
      partners of AR, including AP-2, Pax 3/5 (BSAP), c-Rel, RREB-1, LIII BP, and NPAS2
      were identified. We investigated one unreported AR-associated transcription
      factor, the proto-oncoprotein c-Rel, in detail. C-Rel belongs to the NF-kB/Rel
      families and is persistently active in a number of diseases, including cancer.
      The presence of c-Rel transcript, protein, and its in vitro and in vivo
      association with AR was determined. Co-localization of c-Rel with AR both in
      cytoplasm and nucleus was confirmed by indirect immunofluorescence analysis.
      Chromatin immunoprecipitation data indicated that c-Rel, like AR, is a part of
      the nucleoprotein complex regulating the androgen-responsive prostate-specific
      antigen (PSA) promoter. Overexpression of c-Rel downregulated the promoter
      activity of both PSA and GRE4-TATA-Luc plasmids in LNCaP and COS cells. Analysis
      of AR and c-Rel protein levels indicated that the promoter downregulation was not
      due to reciprocal decrease in the amounts of AR or c-Rel. In summary, we have
      identified several new partners of AR by using the TF-TF array method and have
      provided the first evidence of a functional role for c-Rel in androgen-responsive
      human prostate cancer cells.

PMID- 17011550
TI  - Analysis of apoptotic and survival mediators in the early post-natal and mature
      retina.
AB  - Apoptosis, a cellular process critical to retinal neurogenesis, has been
      implicated in several neurodegenerative disorders. As the retina matures the
      suppression of apoptosis occurs and the emphasis shifts towards survival. To
      identify the cellular changes that bring about this critical shift in the
      balance, we performed an expression analysis of pro- and anti-apoptotic mediators
      in the immature, post-natal day 6 (P6) and the post-mitotic adult P60 mouse
      retina. Laser capture microdissection (LCM) of the P6 and the P60 retina,
      followed by reverse transcriptase-polymerase chain reaction (RT-PCR) was employed
      to elucidate changes in the mRNA expression of Apaf-1, caspase-3 and caspase-9 in
      the individual retinal layers in the young and mature tissue. RT-PCR and Western
      blotting of whole P6 and P60 retinal preparations was carried out to determine
      changes in other caspases and key survival mediators at the mRNA and protein
      level, respectively. Our results demonstrate that each neuronal cell layer in the
      adult retina down-regulates the gene expression of Apaf-1 and caspase-3, and to a
      lesser extent, caspase-9. The protein expression levels of other executioner and
      initiator caspases are also reduced in the adult tissue. Interestingly, XIAP, a
      potent caspase inhibitor, increases in expression in the adult retina.
      Additionally, we demonstrate age-dependent increased expression and activation
      status of the components of the MAPK transduction cascade. Conversely, we observe
      decreased PI3-K and AKT expression and decreased activity of AKT (pAKT) in the
      adult retina. Furthermore, results from RNAi experiments demonstrate an
      additional mechanism of PI3-K regulation in photoreceptor cells. Our findings
      suggest that a survival strategy adopted by the post-mitotic retina involves a
      down-regulation of key pro-apoptotic factors concomitant with changes in
      expression and activation status of certain pro-survival mediators.

PMID- 17011551
TI  - Cerebrospinal fluid of Alzheimer's disease and dementia with Lewy bodies patients
      enhances alpha-synuclein fibril formation in vitro.
AB  - Deposition of alpha-synuclein (alphaS) aggregates inside brain cells is a
      pathological hallmark of several neurodegenerative diseases, including
      Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Recently,
      extracellular alphaS was detected in cerebrospinal fluid (CSF) and plasma of
      humans. We investigated whether CSF influences alphaS aggregation in vitro using
      fluorescence spectroscopy with thioflavin S and electron microscopy. We found
      that CSF obtained from Alzheimer's disease (AD) and DLB patients enhanced the
      alphaS fibril formation compared with tauopathy and non-central nervous system
      disease. Thus, CSF of AD and DLB characterized by aggregation of Abeta or alphaS
      might promote falphaS formation.

PMID- 17011553
TI  - Phospho-specific recognition by 14-3-3 proteins and antibodies monitored by a
      high throughput label-free optical biosensor.
AB  - Label-free detection of molecular interactions has considerable potential in
      facilitating assay development. When combined with high throughput capability, it
      may be applied to small molecule screens for drug candidates. Phosphorylation is
      a key posttranslational process that confers diverse regulation in biological
      systems involving specific protein-protein interactions recognizing the
      phosphorylated motifs. Using a resonant waveguide grating biosensor, the Epic
      mark System, we have developed a generic assay to quantitatively measure phospho
      specific interactions between a trafficking signal-phosphorylated SWTY peptide
      and 14-3-3 proteins or anti-phosphopeptide antibodies. Compared with a solution
      based fluorescence anisotropy assay, our results support that the high throughput
      resonant waveguide grating biosensor system has favorable technical profiles in
      detecting protein-protein interactions that recognize phosphorylated motifs.
      Hence it provides a new generic HTS platform for phospho-detection.

PMID- 17011554
TI  - Profiling of E-cadherin, beta-catenin and Ca(2+) in embryo-uterine interactions
      at implantation.
AB  - Establishment of early pregnancy is promoted by a complex network of signalling
      molecules that mediate cell-to-cell and cell-to-extracellular matrix
      communications between the receptive endometrium and the invasive trophectoderm.
      In this study, we have attempted to evaluate the expression profiles of cadherin
      and catenin during embryo implantation in the mouse. Western blotting studies
      along with immunocytochemical analysis revealed that E-cadherin is expressed
      rather ubiquitously in the uterine epithelial cells, distinct enrichment is
      observed on the apical membrane in the endometrium of peri-implantation uterus
      specifically at the implantation sites and not at the inter-implanation sites.
      beta-Catenin also is upregulated and is specifically restricted to apical
      membrane of epithelial cells of implantation sites. Progesterone induced
      expression of E-cadherin and 17beta-estradiol regulated the expression of catenin
      in implantation-delayed uteri. Interestingly, estradiol imparted negative
      modulation on cadherin expression when co-administered with progesterone. On the
      contrary, trophoblast exhibits a striking down regulation of cadherin, catenin
      and Ca(2+) at peri implanting stage. These observations suggest that the
      trophoblasts exhibited an invasive phenotype while the endometrial epithelium
      displayed an adhesive phenotype during the window of implantation. Thus, embryo
      implantation presents an instance where two interacting surfaces showed mutually
      complementing interaction phenotypes.

PMID- 17011555
TI  - Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization
      pregnancy rates and predictive of fertilization ability.
AB  - OBJECTIVE: To evaluate whether aberrant sperm P1/P2 ratios are predictive of
      abnormal fertilizing ability and are related to in vitro fertilization (IVF)
      outcome. DESIGN: Prospective case-control study. SETTING: University-based
      infertility and IVF clinic. PATIENT(S): Forty-three male infertility patients
      with an abnormally reduced P1/P2 ratio, 251 patients with a normal P1/P2 ratio,
      and 121 patients with an abnormally elevated P1/P2 ratio. INTERVENTION(S): Human
      IVF, the sperm penetration assay (SPA), and sperm protamine quantification via
      nuclear protein extraction, gel electrophoresis, and densitometry analysis. MAIN
      OUTCOME MEASURE(S): Sperm P1/P2 ratios; P1 and P2 quantities; SPA scores; and IVF
      fertilization, embryo-quality, pregnancy, delivery, and spontaneous-abortion
      rates. RESULT(S): Standard IVF fertilization rates and SPA scores were
      significantly reduced in patients with abnormally low and high P1/P2 ratios. In
      vitro fertilization embryo quality was comparable between these groups, but
      pregnancy rates were significantly reduced in patients with abnormally reduced
      P1/P2 ratios. CONCLUSION(S): The P1/P2 ratio has a significant relationship to
      sperm fertilization ability. The relationship between protamines and
      fertilization ability is not understood but may be either a reflection of
      generalized abnormalities during spermiogenesis or an indication of protamine
      deficiency acting as a regulator or checkpoint of spermatogenesis.

PMID- 17011556
TI  - Characterization of estrogen receptors alpha and beta in uterine leiomyoma cells.
AB  - OBJECTIVE: Cellular and subcellular localization of estrogen receptor alpha
      (ERalpha) and estrogen receptor beta (ERbeta) in uterine leiomyomas. DESIGN:
      Retrospective study. SETTING: University of La Laguna (ULL) and Canary University
      Hospital (HUC). PATIENT(S): Premenopausal and postmenopausal women with uterine
      leiomyomas. INTERVENTION(S): Hysterectomy and myomectomy. RESULT(S): Estrogen
      receptor alpha was only present in smooth muscle cells with variation in the
      subcellular location in different leiomyomas. Estrogen receptor beta was widely
      distributed in smooth muscle, endothelial, and connective tissue cells with
      nuclear location in all cases studied; variations were only found in the muscle
      cells for this receptor. CONCLUSION(S): Estrogens operate in leiomyoma smooth
      muscle cells through different receptors, alpha and beta. However they only act
      through the ERbeta in endothelial and connective cells.

PMID- 17011557
TI  - Elective cryopreservation of embryos at the pronucleate stage in women at risk of
      ovarian hyperstimulation syndrome may affect the overall pregnancy rate.
AB  - The aim of this retrospective study was to assess the pregnancy outcome and
      incidence of severe ovarian hyperstimulation syndrome (OHSS) in patients at risk
      of developing OHSS who had embryo cryopreservation at pronucleate stage and
      deferred embryo transfer in a university-affiliated teaching hospital over a 5
      year period. Elective embryo cryopreservation and deferred transfer in patients
      at risk of OHSS does not compromise the cumulative pregnancy rate per patient and
      also results in a low overall incidence of severe OHSS.

PMID- 17011558
TI  - New methods for deriving embryonic stem cell lines: are the ethical problems
      solved?
AB  - The authors argue that a new method of deriving embryonic stem cell lines, which
      could be performed in conjunction with preimplantation genetic diagnosis, is
      unlikely to solve ethical concerns.

PMID- 17011559
TI  - Global sperm deoxyribonucleic acid methylation is unaffected in protamine
      deficient infertile males.
AB  - Sperm protamine-1 (P1) and protamine-2 (P2) concentrations were evaluated
      concomitantly with global DNA methylation patterns in a population of male
      infertility patients. Protamine quantification and immunofluorescence microscopy
      in conjunction with quantitative image analysis revealed no significant
      relationships between the P1/P2 ratio, P1 concentrations, or P2 concentrations
      and levels of global DNA methylation in mature spermatozoa.

PMID- 17011560
TI  - Co-induction of hepatic IGF-I and progranulin mRNA by growth hormone in tilapia,
      Oreochromis mossambiccus.
AB  - Like IGF-I, progranulin (pgrn) is a growth factor involved in tumorigenesis and
      wound healing. We report here the identification and characterization of pgrn
      cDNA in tilapia and the regulation of its expression by growth hormone (GH). The
      tilapia pgrn cDNA was cloned by RT-PCR amplification, using gene specific
      oligonucleotides as amplification primers. The cDNA contains an open reading
      frame encoding a peptide of 206 amino acid residues (aa) that contains a
      presumptive signal peptide (23 aa) and two repeat units of granulin (grn, 51 and
      52 aa, respectively) franked by a GAP of 49 aa and the carboxyl terminus with 31
      aa. The two predicted grn peptides are arranged in tandem repeats interrupted by
      a GAP peptide. RT-PCR analysis revealed that high levels of prgn mRNA were
      present in several tissues such as spleen, gastric cecum, intestine, fat tissue,
      gill, kidney, eye and pancreas, and lower levels in liver, muscle, heart, brain,
      skin and stomach. Administration of a single dose (500 ng/g body weight) of
      recombinant seabream growth hormone (rbGH) by intraperitoneal (ip) injection into
      one-month-old tilapia resulted in an obvious increase of IGF-I and pgrn mRNA (2.7
      fold and 2.5-fold, respectively) in the liver at three hours post-GH treatment.
      The peptide levels of pgrn in the liver of GH-treated fish also were
      substantially induced over controls at 12h post-GH treatment as detected by
      western immuno-blot analysis. The co-induction of IGF-I and pgrn following GH
      treatment may suggest the involvement of pgrn in GH regulated growth in tilapia.

PMID- 17011561
TI  - Ventromedial hypothalamic nucleus lesions disrupt olfactory mate recognition and
      receptivity in female ferrets.
AB  - Previous research showed that ferrets of both sexes rely on the perception of
      conspecifics' body odors to identify and motivate approach towards opposite-sex
      mating partners, and exposure to male body odors stimulated Fos expression in an
      olfactory projection circuit of female, but not male, ferrets that terminates in
      the ventromedial hypothalamic nucleus (VMH). We asked whether the female-typical
      preference of ferrets to approach male as opposed to female body odors in Y-maze
      tests would be disrupted by VMH lesions. Sexually experienced female ferrets were
      ovo-hysterectomized prior to receiving bilateral electrolytic lesions of the VMH,
      the preoptic area/anterior hypothalamus (POA/AH) or a sham operation.
      Subsequently, while receiving estradiol benzoate, females that received either
      complete or partial bilateral lesions of the VMH approached volatile odors from
      an anesthetized male on significantly fewer trials than females given POA/AH
      lesions or a sham operation. Both groups of ferrets with VMH lesion damage
      reliably discriminated between volatile anal scents as well as urinary odors from
      the 2 sexes in home cage habituation/dishabituation tests, suggesting that their
      odor-based sex discrimination remained intact. Females with complete bilateral
      VMH lesions showed significantly lower acceptance of neck gripping from a
      stimulus male (receptivity) and more aggression towards the male than all other
      groups of female subjects. Estrogen-sensitive neurons in the VMH appear to play a
      central role in female-typical neural processing of odor inputs leading to a
      preference to seek out a male sex partner, in addition to facilitating females'
      sexual receptivity.

PMID- 17011562
TI  - Policy on new workforce roles: a discussion paper.
AB  - Addressing workforce issues has increasingly become a central feature of the
      organisation and management of public sector services internationally. The
      introduction of new work roles to public services is one approach advocated in
      response to recruitment and retention difficulties with professional staff and to
      increasingly complex services. This paper aims to critically examine UK's new
      roles policy in a health care context and explore its wider relevance by drawing
      on findings from an action research Ph.D. study aimed at exploring one such new
      role. This deliberately flexible role was held by individuals without a
      recognised qualification but study findings illustrate that, over the time, the
      role came to include the complex discharge planning work with patients previously
      carried out by registered nurses (RNs). The analysis presented highlights
      shortcomings in current new roles policy including the unacknowledged influence
      of competing policy goals; the erroneous assumption that defining who does what
      is clear-cut in practice; the lack of longer-term review of new roles; and the
      incompatibility between role flexibility and needs for role clarity. Policy
      makers, managers and practitioners are urged to acknowledge the subtleties and
      complexities of new work roles in the public sector highlighted by this study.

PMID- 17011563
TI  - Of bedpans and ivory towers? Nurse academics' identities and the sacred and
      profane: a Bernsteinian analysis and discussion paper.
AB  - AIM: In light of debates arising from recent developments in Irish nursing
      education, this paper analyses tensions in the positioning of nursing in academia
      in terms of notions of the sacred and profane, and the symbolic boundaries
      between them, and discusses the implications of this analysis for nurse
      academics' identities. BACKGROUND: The entry of nursing education to the higher
      education sector has occurred against a discursive backcloth of opposition which
      constructs nursing work as either sacred, and under threat from the academy, or
      profane, and unworthy of a place in it. METHOD: Conceptual resources derived from
      the work of Basil Bernstein are deployed to analyse the forces driving the loom
      weaving this discursive backcloth. These forces are conceptualised as deriving
      from deep-seated fears and anxieties sparked by changes in the strength of
      symbolically important boundaries between constructions of the sacred and profane
      in the fields of nursing and higher education. These constructions are
      explicated. FINDINGS: Bernstein regards secure academic identities as inhering in
      strong boundaries between disciplines and between the fields of education and
      work. The transfer of nursing education from health to the higher education
      sector and nurse academics' attempts to articulate a nursing-discipline specific
      knowledge base can be understood in these terms. This analysis challenges nurse
      academics who promote disciplinary eclecticism and those who legitimate academic
      nursing principally in terms of the acquisition of generic and transferable
      lifelong learning skills. CONCLUSIONS: To counter a discourse that constructs
      them as a profane presence in higher education, some nurse academics have
      articulated a discourse of legitimation that constructs (academic) nursing as a
      sacred endeavour. Whether this can provide the grounds of their legitimacy and
      the basis of their careers as distinctively nursing academics is unclear at this
      stage of nursing's development as an academic discipline.

PMID- 17011564
TI  - Turnover factors revisited: a longitudinal study of Taiwan-based staff nurses.
AB  - BACKGROUND: The relationship between employees' intent to stay/leave a position
      and the actual turnover of employees merits further investigation. Most previous
      studies of this relationship have utilized cross-sectional designs to examine
      nurse turnover from a fixed point in time. Research using a longitudinal design
      could increase the ability to predict who will leave, and to identify factors
      that cause turnover behavior. OBJECTIVES: To investigate whether the same
      mechanisms and factors that affect employee's turnover intentions can be applied
      to actual turnover in a longitudinal way in an effort to expose causal
      relationships. DESIGN: After a review of existing literature, we collected
      baseline data on turnover determinants as well as two intervening variables: job
      satisfaction and intent to stay. Three years later, hospital personnel records
      were used to identify the actual turnover of nurses who responded in the first
      wave. SETTINGS: With its 600 beds and metropolitan site, the target hospital
      located in Taichung, Taiwan is representative of Taiwan's general hospitals.
      METHODS: The 412 registered staff nurses (managers excluded) at work in this
      hospital were reached by a mail questionnaire in the first wave. Three years
      later, the turnover data collected in wave two had divided the wave one's 308
      respondents (74.8%) into 132 leavers (42.9%, coded as "1") and 176 stayers
      (57.1%, coded as "0"). The data were then processed by descriptive statistics,
      exploratory factor analysis, multiple regression, and logistic regression.
      RESULTS: As in previous studies of this type, distributive justice, workload,
      resource inadequacy, supervisory support, kinship support, and job satisfaction
      were again proven to be highly associated with intent to stay/leave.
      Nevertheless, with the exception of workload, these indicators worked poorly when
      predicting the actual turnover. CONCLUSIONS: The study confirms earlier findings
      on the relationships among turnover determinants, job satisfaction, and intent to
      stay, and suggests a more comprehensive selection of turnover factors must be
      taken into account when attempting to explain variations in actual turnover.

PMID- 17011565
TI  - A mitochondrial protein affects cell morphology, mitochondrial segregation and
      virulence in Leishmania.
AB  - The single mitochondrion of kinetoplastids divides in synchrony with the nucleus
      and plays a crucial role in cell division. However, despite its importance and
      potential as a drug target, the mechanism of mitochondrial division and
      segregation and the molecules involved are only partly understood. In our quest
      to identify novel mitochondrial proteins in Leishmania, we constructed a hidden
      Markov model from the targeting motifs of known mitochondrial proteins as a tool
      to search the Leishmania major genome. We show here that one of the 17 proteins
      of unknown function that we identified, designated mitochondrial protein X (MIX),
      is an oligomeric protein probably located in the inner membrane and expressed
      throughout the Leishmania life cycle. The MIX gene appears to be essential.
      Moreover, even deletion of one allele from L. major led to abnormalities in cell
      morphology, mitochondrial segregation and, importantly, to loss of virulence. MIX
      is unique to kinetoplastids but its heterologous expression in Saccharomyces
      cerevisiae produced defects in mitochondrial morphology. Our data show that a
      number of mitochondrial proteins are unique to kinetoplastids and some, like MIX,
      play a central role in mitochondrial segregation and cell division, as well as
      virulence.

PMID- 17011566
TI  - Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of
      coronary heart disease among men with metabolic syndrome.
AB  - We tested the hypotheses whether nuclear magnetic resonance (NMR) determined
      lipoprotein particles, insulin and adiponectin, and C-reactive protein (CRP) and
      white blood cell (WBC) count as markers of inflammation predicted risk of
      coronary heart disease (CHD) death among 428 men age 35-57 years with metabolic
      syndrome (MetSyn) in a matched case control study within the multiple risk factor
      intervention trial. Blood samples collected at entry into the study and stored at
      -60 degrees C were obtained from central storage for blood analyte analysis. Two
      hundred and fourteen men with MetSyn who died of CHD were matched with 214 men
      with MetSyn who did not die of CHD during 18 years of follow-up. Cases were
      matched to controls on age, study group, number of factors present in the MetSyn,
      and presence or absence of a nonfatal CVD event during the trial. Mortality
      follow-up was determined using the National Death Index. Higher levels of high
      density lipoprotein particles (HDL-P), especially medium-sized HDL-P [hazard
      ratio (95% confidence interval) 0.45 (0.25-0.83, P<0.01), quartile 1 as compared
      to quartile 4], were associated with lower risk of CHD death. Low density
      lipoprotein (LDL) particles were not associated with increased risk of CHD.
      Elevated LDL cholesterol (LDL-C), smoking and WBC count were, but levels of
      adiponectin, insulin and CRP were not significantly related to CHD death. In
      multivariate models adjusting for smoking and LDL-C, medium HDL-P and WBC count
      remained independent predictors of CHD death. Number of HDL particles, especially
      medium-sized HDL particles and WBC count were independent predictors of CHD death
      among men with MetSyn.

PMID- 17011568
TI  - Layer-by-layer assembly of intact polydiacetylene vesicles with retained chromic
      properties.
AB  - Photopolymerized vesicles of 10,12-pentacosadiynoic acid (PPCDA) were
      successfully assembled into polyelectrolyte multilayer (PEM) thin films using
      either chitosan or poly(ethylenimine) (PEI) as a polycation. The PEM films
      assembled from chitosan or PEI polycation retained the blue color of PPCDA
      vesicles. For the blue films, an increase in absorbance at 635 nm as a function
      of the number of deposited layers of PPCDA vesicles was observed, confirming the
      uniform layer-by-layer deposition process. The spherical structures of PPCDA
      vesicles, as well as their important colorimetric responses to solvent (ethanol),
      pH, and temperature, are retained in the PEM film. Compared to the vesicles
      dispersed in water, the PEM films are much more stable to aging. Layer-by-layer
      assembly thus provides a convenient means to prepare colorimetric sensing
      devices, with extended shelf life, from polydiacetylene vesicles.

PMID- 17011567
TI  - Metabolic syndrome in a sub-Saharan African setting: central obesity may be the
      key determinant.
AB  - OBJECTIVES: To determine, in a rural and urban population in Cameroon, the
      prevalence of the metabolic syndrome (MS) using three definitions and to assess
      the association between components of the MS, central obesity and HOMA insulin
      resistance (HOMA-IR) index. METHODS: A representative sample of 1573 adults (638
      rural, 935 urban) were interviewed on their personal medical history. Blood
      pressure and anthropometric measures used standardised methods. After an
      overnight fast, blood samples were collected before and 2h after an OGTT and
      plasma glucose, plasma insulin and blood lipids determined. Modified WHO, NCEP
      ATP III, and IDF definitions of the MS were used. RESULTS: Central obesity was
      the most prevalent component of the syndrome, but prevalence varied widely
      according to the definition used. Hypertriglyceridemia was almost non-existent.
      The highest prevalence of the MS was with the WHO definition and the lowest with
      the NCEP-ATP III definition. Central obesity was more tightly associated with
      components of the MS than was HOMA-IR. CONCLUSIONS: The prevalence of the MS
      varied greatly by rural/urban residence with the various definitions used.
      Central obesity appears to be the key determinant of the prevalence of the MS in
      sub Saharan Africa. Many MS definitions may not be appropriate for African
      populations.

PMID- 17011570
TI  - Dynamics of thin liquid films on surfaces with a time-periodic wettability.
AB  - The dynamics of thin liquid films on surfaces whose wettability changes in a time
      periodic manner are examined in this work. A nonlinear evolution equation based
      on the lubrication approximation is used to describe the film height, and
      attractions due to van der Waals forces are incorporated. Film wettability is
      varied through an imposed sinusoidal modulation of the Hamaker constant. A linear
      stability analysis predicts that if the mean Hamaker constant is negative,
      disturbances at the film surface will eventually decay regardless of the
      amplitude and frequency of the oscillation. However, numerical solution of the
      evolution equation shows that the film can rupture at a given frequency if the
      amplitude is sufficiently large. The associated characteristic wavelength can be
      predicted from results for constant-wettability surfaces if an appropriate
      effective Hamaker constant is used. For positive mean Hamaker constants, film
      rupture can be accelerated, delayed, or prevented depending on how the Hamaker
      constant changes early in the oscillation cycle. The effects of spatial gradients
      in wettability are also considered, and it is found that oscillation can delay
      but not prevent rupture. Inclusion of short-range repulsive forces leads to the
      formation of droplet-like structures separated by ultra-thin films, but this can
      be prevented by sufficiently large and slow oscillations of the Hamaker constant.
      The results of this work may find use in applications that make use of surfaces
      whose wettability can be controlled by external stimuli.

PMID- 17011569
TI  - Effect of electrochemical oxidation of activated carbon fiber on competitive and
      noncompetitive sorption of trace toxic metal ions from aqueous solution.
AB  - A viscose-rayon-based activated carbon cloth (ACC) was electrochemically oxidized
      to enhance its cation sorption capacity for comparison with as-received ACC. The
      ACCs were characterized by sodium capacity measurement, pH titration, zeta
      potential measurement, elemental analysis, Brunauer-Emmet-Teller surface area,
      and pore size distribution. Batch sorption experiments showed that
      electrochemically oxidized ACC (EO) is more effective for the removal of lead and
      copper ions compared to unoxidized ACC (UO) for both competitive and
      noncompetitive sorption. For electrochemically oxidized fibers the copper and
      lead sorption capacities of ACC increased 17 and 4 times, respectively, for
      noncompetitive sorption and 8.8 and 8.6 times, respectively, for competitive
      sorption. However, reduction in the sorption capacities for both metals was
      observed for the competitive sorption. The sorption of lead and copper onto EO
      was by ion exchange, while that onto UO was likely to be due to surface complex
      formation. The affinity order of the two metal ions sorbed by UO and EO is
      Pb(2+)>Cu(2+). The effect of pH on sorption isotherms indicated that metal uptake
      increased with an increase in solution pH.

PMID- 17011571
TI  - Concomitant real-time monitoring of intracellular reactive oxygen species and
      mitochondrial membrane potential in individual living promonocytic cells.
AB  - Reactive oxygen species (ROS) have recently been shown to be involved in multiple
      physiological responses through modulation of signaling pathways. Inappropriate
      production of these radicals, and their metabolites, leads to the development of
      various pathologies. Free radicals can induce both positive and negative effects
      in cells, and their metabolic pathways are very complex. Hence, it is crucial to
      be able to simultaneously and directly determine their production dynamics and
      concentrations in individual living cells, in physiological or pathological
      states, and in response to drugs. The aim of the present study was to monitor in
      real time the rates of ROS generation in promonocytic cells upon stimulation with
      hydrogen peroxide and oxidized lipid. Quantitative detection of intracellular ROS
      concentration in intact living U937 cells was performed by fluorescence intensity
      (FI) and polarization (FP) measurements utilizing the Optical LiveCell Array
      technology. The "dihydro" derivative probes of fluorescein (DCF-DA) and rhodamine
      (DHR123) were used to assess the intracellular levels of ROS. Each probe molecule
      exhibited a characteristic FI and FP in its non-fluorescent or oxidized form.
      Analysis of the temporal relationship between the kinetics of ROS generation and
      the onset of changes in mitochondrial membrane potential shows high variability
      within a cell population with regard to both processes. The data demonstrated
      that temporal measurement of ROS generation, in identifiable individual cells,
      reveals kinetic behavior that otherwise would be undetected.

PMID- 17011573
TI  - PCNA activates the Holliday junction endonuclease Hjc.
AB  - The resolving enzyme Hjc, which cleaves Holliday junctions with a high degree of
      structural specificity, is conserved in all archaea. Like RuvC in Escherichia
      coli, Hjc functions in the related processes of homologous recombination and
      double-strand break repair. In bacteria, the RuvAB complex binds Holliday
      junctions and catalyses ATP-dependent branch migration, but the equivalent
      proteins in archaea and eukarya are unknown. Here, we demonstrate that Hjc from
      Sulfolobus solfataricus forms a physical interaction with the sliding clamp PCNA
      via a C-terminal PCNA-interacting peptide (PIP) motif in Hjc. PCNA stimulates the
      Holliday junction cleavage activity of Hjc in vitro, and deletion of the PIP
      motif abrogates this effect. This is the first report of a functional interaction
      between a sliding clamp and a junction-resolving enzyme, and raises the
      possibility that PCNA could recruit a variety of different proteins to act on
      Holliday junctions in vivo.

PMID- 17011572
TI  - Class II HDACs mediate CaMK-dependent signaling to NRSF in ventricular myocytes.
AB  - We recently reported that a transcriptional repressor, neuron-restrictive
      silencer factor (NRSF), represses expression of fetal cardiac genes, including
      atrial and brain natriuretic peptide (ANP and BNP), by recruiting class I histone
      deacetylase (HDAC) and that attenuation of NRSF-mediated repression contributes
      to the reactivation of fetal gene expression during cardiac hypertrophy. The
      molecular mechanism by which the activity of the NRSF-HDAC complex is inhibited
      in cardiac hypertrophy remains unresolved, however. In the present study, we show
      that class II HDACs (HDAC4 and 5), which are Ca/calmodulin-dependent kinase
      (CaMK)-responsive repressors of hypertrophic signaling, associate with NRSF and
      participate in NRSF-mediated repression. Blockade of the CaMK-class II HDAC
      signaling pathway using a CaMK-resistant HDAC5 mutant, a CaMK inhibitor (KN62) or
      a dominant-negative CaMK mutant inhibited ET-1-inducible ANP and BNP promoter
      activity, but that inhibitory effect was abolished by mutation of the neuron
      restrictive silencer element (NRSE) within the ANP and BNP promoter. In addition,
      adenovirus-mediated expression of a dominant-negative NRSF mutant abolished the
      inhibitory effect of KN62 on ET-1-inducible endogenous ANP gene expression in
      ventricular myocytes. Finally, the interaction between NRSF and class II HDACs
      was decreased in both in vitro and in vivo models of cardiac hypertrophy. These
      findings show that ET-1-induced CaMK signaling disrupts class II HDAC-NRSF
      repressor complexes, thereby enabling activation of ANP and BNP gene
      transcription in ventricular myocytes, and shed light on a novel mechanism by
      which the fetal cardiac gene program is reactivated.

PMID- 17011574
TI  - The evolution of catalytic efficiency and substrate promiscuity in human theta
      class 1-1 glutathione transferase.
AB  - Theta class glutathione transferases (GST) from various species exhibit markedly
      different catalytic activities in conjugating the tripeptide glutathione (GSH) to
      a variety of electrophilic substrates. For example, the human theta 1-1 enzyme
      (hGSTT1-1) is 440-fold less efficient than the rat theta 2-2 enzyme (rGSTT2-2)
      with the fluorogenic substrate 7-amino-4-chloromethyl coumarin (CMAC). Large
      libraries of hGSTT1-1 constructed by error-prone PCR, DNA shuffling, or
      saturation mutagenesis were screened for improved catalytic activity towards CMAC
      in a quantitative fashion using flow cytometry. An iterative directed evolution
      approach employing random mutagenesis in conjunction with homologous
      recombination gave rise to enzymes exhibiting up to a 20,000-fold increase in
      k(cat)/K(M) compared to hGSTT1-1. All highly active clones encoded one or more
      mutations at residues 32, 176, or 234. Combinatorial saturation mutagenesis was
      used to evaluate the full complement of natural amino acids at these positions,
      and resulted in the isolation of enzymes with catalytic rates comparable to those
      exhibited by the fastest mutants obtained via directed evolution. The substrate
      selectivities of enzymes resulting from random mutagenesis, DNA shuffling, and
      combinatorial saturation mutagenesis were evaluated using a series of distinct
      electrophiles. The results revealed that promiscuous substrate activities arose
      in a stochastic manner, as they did not correlate with catalytic efficiency
      towards the CMAC selection substrate. In contrast, chimeric enzymes previously
      constructed by homology-independent recombination of hGSTT-1 and rGSTT2-2
      exhibited very different substrate promiscuity profiles, and showed a more
      defined relationship between evolved and promiscuous activities.

PMID- 17011575
TI  - X-ray structures of the microglia/macrophage-specific protein Iba1 from human and
      mouse demonstrate novel molecular conformation change induced by calcium binding.
AB  - The ionized calcium-binding adaptor molecule 1 (Iba1) with 147 amino acid
      residues has been identified as a calcium-binding protein, expressed specifically
      in microglia/macrophages, and is expected to be a key factor in membrane
      ruffling, which is a typical feature of activated microglia. We have determined
      the crystal structure of human Iba1 in a Ca(2+)-free form and mouse Iba1 in a
      Ca(2+)-bound form, to a resolution of 1.9 A and 2.1 A, respectively. X-ray
      structures of Iba1 revealed a compact, single-domain protein with two EF-hand
      motifs, showing similarity in overall topology to partial structures of the
      classical EF-hand proteins troponin C and calmodulin. In mouse Iba1, the second
      EF-hand contains a bound Ca(2+), but the first EF-hand does not, which is often
      the case in S100 proteins, suggesting that Iba1 has S100 protein-like EF-hands.
      The molecular conformational change induced by Ca(2+)-binding of Iba1 is
      different from that found in the classical EF-hand proteins and/or S100 proteins,
      which demonstrates that Iba1 has an unique molecular switching mechanism
      dependent on Ca(2+)-binding, to interact with target molecules.

PMID- 17011576
TI  - Autocatalytic activation of influenza hemagglutinin.
AB  - Enveloped viruses contain surface proteins that mediate fusion between the viral
      and target cell membranes following an activating stimulus. Acidic pH induces the
      influenza virus fusion protein hemagglutinin (HA) via irreversible refolding of a
      trimeric conformational state leading to exposure of hydrophobic fusion peptides
      on each trimer subunit. Herein, we show that cells expressing fowl plague virus
      HA demonstrate discrete switching behavior with respect to the HA conformational
      change. Partially activated states do not exist at the scale of the cell,
      activation of HA leads to aggregation of cell surface trimers, and newly
      synthesized HA refold spontaneously in the presence of previously activated HA.
      These observations imply a feedback mechanism involving self-catalyzed refolding
      of HA and thus suggest a mechanism similar to the autocatalytic refolding and
      aggregation of prions.

PMID- 17011577
TI  - Chelerythrine and sanguinarine dock at distinct sites on BclXL that are not the
      classic BH3 binding cleft.
AB  - The ratio of the levels of pro-survival and pro-apoptotic members of the Bcl-2
      protein family is thought to be an important regulatory factor for determining
      the sensitivity of the mammalian cells to apoptotic stimuli. High levels of
      expression of pro-survival members such as Bcl(XL) in human cancers were
      frequently found to be a good prognostic indicator predicting poor response to
      chemotherapy. The pro-survival members of the Bcl-2 family mediate their effects
      through heterodimerization with the BH3 region of the pro-apoptotic members.
      Structural analyses of the binding complex of the BH3 peptide and Bcl(XL) showed
      that a hydrophobic groove termed the BH3 binding cleft is the docking site for
      the BH3 region. Chemical mimetics of the BH3 region such as BH3I-1 that target
      the BH3 binding cleft indeed exhibit pro-apoptotic activities. Chelerythrine
      (CHE) and sanguinarine (SAN) are natural benzophenanthridine alkaloids that are
      structurally homologous to each other. CHE was previously identified as an
      inhibitor of Bcl(XL) function from a high-throughput screen of natural products,
      but its mode of interaction with Bcl(XL) is not known. By determining the effect
      of site-directed mutagenesis on ligand binding and using saturation transfer
      difference (STD) NMR experiments, we have verified locations of these docked
      ligands. Surprisingly, CHE and SAN bind separately at the BH groove and BH1
      region of Bcl(XL) respectively, different from the BH3 binding cleft where other
      known inhibitors of Bcl(XL) target. Interestingly, certain residues on the
      flexible loop between helices alpha1 and alpha2 of Bcl(XL) are also perturbed
      upon CHE, but not SAN or BH3I-1 binding. Although CHE and SAN are similarly
      effective as BH3I-1 in displacing bound BH3 peptide, they are much more effective
      in inducing apoptosis, raising the possibility that CHE and SAN might be able to
      antagonize other pro-survival mechanisms in addition to the one that involves BH3
      region binding.

PMID- 17011578
TI  - Transcriptional repressor CcpN from Bacillus subtilis compensates asymmetric
      contact distribution by cooperative binding.
AB  - Carbon catabolite repression in Bacillus subtilis is carried out mainly by the
      major regulator CcpA. In contrast, sugar-dependent repression of three genes, sr1
      encoding a small untranslated RNA, and two genes, gapB and pckA, coding for
      gluconeogenic enzymes is mediated by the recently identified transcriptional
      repressor CcpN. Since previous DNase I footprinting yielded only basic
      information on the operator sequences of CcpN, chemical interference footprinting
      studies were performed for a precise contact mapping. Methylation interference,
      potassium permanganate and hydroxylamine footprinting were used to identify all
      contacted residues in both strands in the three operator sequences. Furthermore,
      ethylation interference experiments were performed to identify phosphate residues
      essential for CcpN binding. Here, we show that each operator has two binding
      sites for CcpN, one of which was always contacted more strongly than the other.
      The three sites that exhibited close contacts were very similar in sequence, with
      only a few slight variations, whereas the other three corresponding sites showed
      several deviations. Gel retardation assays with purified CcpN demonstrated that
      the differences in contact number and strength correlated well with significantly
      different K(D) values for the corresponding single binding sites. However,
      quantitative DNase I footprinting of whole operator sequences revealed
      cooperative binding of CcpN that, apparently, compensated the asymmetric contact
      distribution. Based on these data, possible consequences for the repression
      mechanism of CcpN are discussed.

PMID- 17011579
TI  - Mapping of the auto-inhibitory interactions of protein kinase R by nuclear
      magnetic resonance.
AB  - The dsRNA-dependent protein kinase (PKR) is a key mediator of the anti-viral and
      anti-proliferative effects of interferon. Unphosphorylated PKR is characterized
      by inhibitory interactions between the kinase and RNA binding domains (RBDs), but
      the structural details of the latent state and its unraveling during activation
      are not well understood. To study PKR regulation by NMR we assigned a large
      portion of the backbone resonances of the catalytically inactive K296R kinase
      domain, and performed (15)N-heteronuclear single quantum coherence (HSQC)
      titrations of this kinase domain with the RBDs. Chemical shift perturbations in
      the kinase indicate that RBD2 binds to the substrate eIF2alpha docking site in
      the kinase C-lobe. Consistent with these results, a mutation in the eIF2alpha
      docking site, F495A, displays weaker interactions with the RBD. The full-length
      RBD1+2 binds more strongly to the kinase domain than RBD2 alone. The observed
      chemical shift changes extend from the eIF2alpha binding site into the kinase N
      lobe and inside the active site, consistent with weak interactions between the N
      terminal part of the RBD and the kinase.

PMID- 17011581
TI  - Evaluation of energetic and dynamic coupling networks in a PDZ domain protein.
AB  - A number of computational and experimental studies have identified intramolecular
      communication "pathways" or "networks" important for transmitting allostery.
      Here, we have used mutagenesis and NMR relaxation methods to investigate the
      scope and nature of the communication networks found in the second post-synaptic
      density-95/discs large/zonula occludens-1 (PDZ) domain of the human protein
      tyrosine phosphatase 1E protein (hPTP1E) (PDZ2). It was found that most mutations
      do not have a significant energetic contribution to peptide ligand binding. Three
      mutants that showed significant changes in binding also displayed context
      dependent dynamic effects. Both a mutation at a partially exposed site (H71Y) and
      a buried core position (I35V) had a limited response in side-chain (2)H-based
      dynamics when compared to wild-type PDZ2. In contrast, a change at a second core
      position (I20F) that had previously been shown to be part of an energetic and
      dynamic network, resulted in extensive changes in side-chain dynamics. This
      response is reminiscent to that seen previously upon peptide ligand binding.
      These results shed light on the nature of the PDZ2 dynamic network and suggest
      that position 20 in PDZ2 acts as a "hub" that is energetically and dynamically
      critical for transmitting changes in dynamics throughout the PDZ domain.

PMID- 17011580
TI  - Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of
      the receptor tyrosine kinase MuSK.
AB  - Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed exclusively
      in skeletal muscle, where it is required for formation of the neuromuscular
      junction. MuSK is activated by agrin, a neuron-derived heparan sulfate
      proteoglycan. Here, we report the crystal structure of the agrin-responsive first
      and second immunoglobulin-like domains (Ig1 and Ig2) of the MuSK ectodomain at
      2.2 A resolution. The structure reveals that MuSK Ig1 and Ig2 are Ig-like domains
      of the I-set subfamily, which are configured in a linear, semi-rigid arrangement.
      In addition to the canonical internal disulfide bridge, Ig1 contains a second,
      solvent-exposed disulfide bridge, which our biochemical data indicate is critical
      for proper folding of Ig1 and processing of MuSK. Two Ig1-2 molecules form a non
      crystallographic dimer that is mediated by a unique hydrophobic patch on the
      surface of Ig1. Biochemical analyses of MuSK mutants introduced into MuSK(-/-)
      myotubes demonstrate that residues in this hydrophobic patch are critical for
      agrin-induced MuSK activation.

PMID- 17011582
TI  - A cost analysis of a smoke alarm installation and fire safety education program.
AB  - INTRODUCTION: While smoke alarm installation programs can help prevent
      residential fire injuries, the costs of running these programs are not well
      understood. METHOD: We conducted a retrospective cost analysis of a smoke alarm
      installation program in 12 funded communities across four states. Costs included
      financial and economic resources needed for training, canvassing, installing, and
      following-up, within four cost categories: (a) personnel, (b) transportation, (c)
      facility, and (d) supplies. RESULTS: Local cost per completed home visit averaged
      214.54 dollars, with an average local cost per alarm installed of 115.02 dollars.
      Combined state and local cost per alarm installed across all four states averaged
      132.15 dollars. For every 1% increase in alarm installation, costs per alarm
      decrease by 1.32 dollars. CONCLUSIONS: As more smoke alarms are installed, the
      average installation cost per alarm decreases. By demonstrating effective
      economies of scale, this study suggests that smoke alarm programs can be
      implemented efficiently and receive positive economic returns on investment.

PMID- 17011583
TI  - Paraneoplastic cerebellar degeneration: Yo-expressing tumor revealed after a 5
      year follow-up with FDG-PET.
AB  - We report a patient with anti-Yo associated paraneoplastic cerebellar
      degeneration (PCD) whose tumor was demonstrated 5 years after developing PCD and
      had strong expression of Yo (cdr2) antigen. Review of this case along with
      clinical series and studies of tumor growth rates question the effectiveness of
      the anti-tumor immune response. These studies and similar cases suggest that the
      tumor may trigger the anti-Yo immune response at microscopic stages of
      development. An overwhelming majority of anti-Yo positive patients eventually
      develop a detectable malignancy, which argues in favor of a poorly effective or
      non-sustained anti-tumor immune response.

PMID- 17011584
TI  - Oscillatory cerebral hemodynamics--the macro- vs. microvascular level.
AB  - The phase shift between oscillations of blood pressure (BP) and Doppler middle
      cerebral artery flow velocity (MCAFV) reflects continuous cerebral autoregulatory
      action. It is not known whether a similar phase shift exists for cortical
      hemodynamics ('microvascular level') assessed by near infrared spectroscopy
      (NIRS) and what the effects are of pathological conditions. This study
      investigates the phase relations between oscillations of BP, MCAFV and NIRS
      parameters in 38 healthy older adults and 28 patients with unilateral severe
      obstructive carotid disease. BP was recorded noninvasively by finger
      plethysmography. Stable 0.1 Hz oscillations of all hemodynamic parameters were
      induced by regular breathing at a rate of 6/min. Basic results were that: (1) BP
      induced cortical microvascular oscillations (NIRS) follow those of macrovascular
      oscillations (MCAFV) with a phase of 80-90 degrees (corresponding to 2-2.5 s at
      0.1 Hz), most likely reflecting a transit time phenomenon; (2) oxy- and
      deoxyhemoglobin thereby oscillate in counterphase; (3) hemodynamic compromise in
      carotid obstruction leads to (a) delayed NIRS oscillations in comparison to BP
      which are highly correlated to a shorter phase lead of MCAFV against BP and (b) a
      decoupling of the oxy-/deoxyhemoglobin counterphase to 240 degrees . Cortical
      hemodynamic responses to BP oscillations follow specific phase relationships due
      to cerebral autoregulatory action and circulatory transit times. With hemodynamic
      impairment, as in unilateral carotid obstruction, these phases are significantly
      changed reflecting disturbed autoregulation.

PMID- 17011585
TI  - Ipsilateral silent period: a marker of callosal conduction abnormality in early
      relapsing-remitting multiple sclerosis?
AB  - OBJECTIVE: The corpus callosum (CC) is commonly affected in multiple sclerosis
      (MS). The ipsilateral silent period (iSP) is a putative electrophysiological
      marker of callosal demyelination. The purpose of this study was to re-assess,
      under recently established optimised protocol conditions [Jung P., Ziemann U.
      Differences of the ipsilateral silent period in small hand muscles. Muscle Nerve
      in press.], its diagnostic sensitivity in MS, about which conflicting results
      were reported in previous studies. METHODS: ISP measurements (onset, duration,
      and depth) were obtained in the abductor pollicis brevis (APB) muscle of either
      hand in 49 patients with early relapsing-remitting MS (RRMS) (mean EDSS, 1.3).
      Standard central motor conduction times to the APB (CMCT(APB)) and tibial
      anterior muscles (CMCT(TA)), and magnetic resonance images (MRI) were also
      obtained. RESULTS: ISP measurements showed a similar diagnostic sensitivity
      (28.6%) as CMCT(APB) (24.5%), while diagnostic sensitivities of CMCT(TA) (69.4%)
      and MRI of the CC (78.6%) were much higher. Prolongation of iSP duration was the
      most sensitive single iSP measure. ISP prolongation occurred more frequently when
      CMCT(APB) to the same hand was also prolonged (40.0% vs. 8.4%, p<0.0001). The
      correlation between iSP duration and CMCT(APB) was significant (Pearson's r=0.24,
      p<0.02), suggesting that iSP duration can be contaminated by demyelination of the
      contralateral corticospinal tract. ISP duration did not correlate with MRI
      abnormalities of the CC. CONCLUSIONS: ISP measures are neither a sensitive nor a
      specific marker of callosal conduction abnormality in early RRMS.

PMID- 17011587
TI  - Monotonicity of interleukin-1 receptor-ligand binding with respect to antagonist
      in the presence of decoy receptor.
AB  - We consider the interaction between interleukin-1 IL-1, its receptor IL-1RI, the
      receptor antagonist IL-1Ra and a decoy receptor (or trap) that binds both with
      the ligand and the antagonist. We study how the interaction between IL-1Ra and
      the decoy receptor influences the effect of either reagent on reducing the
      equilibrium concentration of the receptor-ligand complex. We obtain that, given a
      certain relationship among the equilibrium constants and the total concentrations
      of solutes, IL-1Ra can reverse the effect of the decoy receptor of decreasing the
      equilibrium concentration of the receptor-ligand complex. This finding derives
      from a mathematical result applicable to any reversible chemical reaction system
      comprising four species arranged in a square such that each species binds its two
      immediate neighbors. The result gives the monotonicity of the equilibrium
      concentrations of the complex species as functions of the total concentrations of
      the simple species.

PMID- 17011586
TI  - GABA(A)-receptor mRNA expression in the prefrontal and temporal cortex of ALS
      patients.
AB  - There is evidence that excitotoxic cell death is involved in the pathogenesis of
      amyotrophic lateral sclerosis (ALS). Electrophysiological and histological
      studies support the pathophysiological concept of an impaired inhibitory, namely
      GABAergic, control of the motoneurons in the cerebral cortex of ALS patients.
      Recently, pathological, neuropsychological and functional imaging data have
      challenged the view that ALS is a disorder restricted to the motor system. The
      aim of our study was to investigate the expression of the most abundant GABA(A)
      receptor subunit mRNAs and the GABA synthesizing enzyme glutamic acid
      decarboxylase (GAD) in the prefrontal, temporal, occipital and cerebellar cortex
      of ALS patients compared to tissue of control persons. We performed in situ
      hybridization histochemistry (ISH) on human post-mortem cortex sections of ALS
      patients (n=5) and age-matched controls with no history of neurological disease
      (n=5). In the prefrontal and temporal cortex of ALS patients, we detected
      significantly reduced mRNA expression of the alpha1-subunit, while the GABA
      synthesizing enzyme glutamic acid decarboxylase (GAD) was significantly
      upregulated in these regions. In the occipital and cerebellar cortex, we did not
      see disease-specific differences of the mRNA expression of the investigated
      subunits.

PMID- 17011588
TI  - Pair approximations and the inclusion of indirect transmission: theory and
      application to between farm transmission of Salmonella.
AB  - The spatial-temporal dynamics of farm animal diseases depend both on disease
      specific processes and the underlying contact network between farms. Indirect
      transmission via free-living bacteria in the environment is an important
      transmission route and contributes significantly to the dynamics. The pair-wise
      model has been developed to include both direct transmission and indirect
      transmission via free stages. The model is compared with stochastic simulations
      of epidemics on contact networks. The network framework is applied to the
      investigation of the epidemiological dynamics of between-herd transmission of
      Salmonella spp. The main results help to explain differences in observed
      epidemiological patterns and to identify possible causes for different strains of
      Salmonella developing so much variation in their infection dynamics in UK dairy
      herds. Numerical results show that shorter infectious period, more persistent
      immune response and more rapid removal of faeces result in a lower prevalence of
      infection and a greater tendency for (damped) oscillation. A possible control
      strategy is consequently suggested. Furthermore, the effect of network structure
      on long-term dynamics is examined.

PMID- 17011589
TI  - Alpha-lipoic acid: an inhibitor of secretory phospholipase A2 with anti
      inflammatory activity.
AB  - Alpha-lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are
      powerful antioxidants both in hydrophilic and lipophylic environments with
      diverse pharmacological properties including anti-inflammatory activity. The
      mechanism of anti-inflammatory activity of ALA and DHALA is not known. The
      present study describes the interaction of ALA and DHALA with pro-inflammatory
      secretory PLA(2) enzymes from inflammatory fluids and snake venoms. In vitro
      enzymatic inhibition of sPLA(2) from Vipera russellii, Naja naja and partially
      purified sPLA(2) enzymes from human ascitic fluid (HAF), human pleural fluid
      (HPF) and normal human serum (HS) by ALA and DHLA was studied using (14)C-oleate
      labeled Escherichia coli as the substrate. Biophysical interaction of ALA with
      sPLA(2) was studied by fluorescent spectral analysis and circular dichroism
      studies. In vivo anti-inflammatory activity was checked using sPLA(2) induced
      mouse paw edema model. ALA but not DHLA inhibited purified sPLA(2) enzymes from
      V. russellii, N. naja and partially purified HAF, HPF and HS in a dose dependent
      manner. This data indicated that ALA is critical for inhibition. IC(50) value
      calculated for these enzymes ranges from 0.75 to 3.0 microM. The inhibition is
      independent of calcium and substrate concentration. Inflammatory sPLA(2) enzymes
      are more sensitive to inhibition by ALA than snake venom sPLA(2) enzymes. ALA
      quenched the fluorescence intensity of sPLA(2) enzyme in a dose dependent manner.
      Apparent shift in the far UV-CD spectra of sPLA(2) with ALA indicated change in
      its alpha-helical confirmation and these results suggest its direct interaction
      with the enzyme. ALA inhibits the sPLA(2) induced mouse paw edema in a dose
      dependent manner and confirms the sPLA(2) inhibitory activity in vivo also. These
      data suggest that ALA may act as an endogenous regulator of sPLA(2) enzyme
      activity and suppress inflammatory reactions.

PMID- 17011590
TI  - Biomarkers in environmental and human health risk assessment.
AB  - Marine pollution is a major threat to human and environmental health. Given the
      complexity of function of marine and coastal ecosystems, it is unlikely that a
      balanced view of the nature and extent of risk will easily be achieved if human
      and environmental risk assessments continue to be conducted in isolation. Here,
      the integration of assessment protocols is advocated as a holistic means of
      improving risk management. Biomarkers can provide the common conceptual framework
      and measurable endpoints necessary for successful integration. Examples are given
      of the ways in which suites of biomarkers encompassing molecular change, cellular
      pathology and physiological impairment can be developed and adapted for human and
      ecological scenarios. By placing a greater emphasis on the health status of
      impacted biota, it is more likely that risk assessment will develop the
      efficiency, reliability and predictive power to adapt to the unforeseen
      environmental threats that are an inevitable consequence of human development and
      global change.

PMID- 17011591
TI  - Defining and detecting undesirable disturbance in the context of marine
      eutrophication.
AB  - An understanding of undesirable disturbance to the balance of organisms is needed
      to diagnose marine eutrophication as defined by EU Directives and OSPAR. This
      review summarizes the findings of the UK Defra-funded Undesirable Disturbance
      Study Team, which concluded that 'an undesirable disturbance is a perturbation of
      a marine ecosystem that appreciably degrades the health or threatens the
      sustainable human use of that ecosystem'. A methodology is proposed for detecting
      disturbance of temperate salt-water communities dominated by phytoplanktonic or
      phytobenthic primary producers. It relies on monitoring indicators of ecosystem
      structure and vigour, which are components of health. Undesirable disturbance can
      be diagnosed by accumulating evidence of ecohydrodynamic type-specific changes
      in: (i) bulk indicators; (ii) frequency statistics; (iii) flux measurements; (iv)
      structural indicators; and (v) indicator species. These are exemplified by (i)
      chlorophyll, transparency, dissolved oxygen, and opportunistic seaweed cover;
      (ii) HABs frequency; (iii) primary production; (iv) benthic and planktonic
      'trophic indices'; (v) seagrasses and Nephrops norvegicus. Ecological Quality
      Objectives are proposed for some of these. Linking the diagnosis to
      eutrophication requires correlation of changes with nutrient enrichment. The
      methodology, which requires the development of a plankton community index and
      emphasizes the importance of primary production as an indicator of vigour, can be
      harmonized with the EU Water Framework Directive and OSPAR's Strategy to Combat
      Eutrophication.

PMID- 17011592
TI  - Neuron firing in driven nonlinear integrate-and-fire models.
AB  - Statistical properties of neuron firing are studied in the framework of a
      nonlinear leaky integrate-and-fire model that is driven by a slow periodic
      subthreshold signal. The firing events are characterized by first passage time
      densities. The experimentally better accessible interspike interval density
      generally depends on the sojourn times in a refractory state of the neuron. This
      aspect is not part of the integrate-and-fire model and must be modelled
      additionally. For a large class of refractory dynamics, a general expression for
      the interspike interval density is given and further evaluated for the two cases
      with an instantaneous resetting (i.e. no refractory state) and a refractory state
      possessing a deterministic lifetime. First passage time densities and interspike
      interval densities following from the proposed theory compare favorably with
      precise numerical simulations.

PMID- 17011593
TI  - Coalescent theory for a completely random mating monoecious population.
AB  - Consider a large random mating monoecious diploid population that has N
      individuals in each generation. Let us assume that at time 0 a random sample of
      n<<N copies of a gene are taken from this population. It is also assumed that
      G(1),...,G(N), the numbers of successful gametes produced by parents 1,...,N, are
      exchangeable random variables. It is shown that if time is measured backward in
      units of 8N/E[G(1)(G(1)-1)]=2Ne generations, where Ne is the effective population
      size, the separate copies of a gene ancestral to those observed at time 0 are
      almost certain to come from separate individuals as Ne -->infinity. It is then
      possible to obtain a generalization of coalescent theory for haploid populations
      if the distribution of G1 has a finite second moment and E[G(1)(3)]/N-->0 as N-
      >infinity.

PMID- 17011595
TI  - Effects of 1.8 GHz radiofrequency field on DNA damage and expression of heat
      shock protein 70 in human lens epithelial cells.
AB  - To investigate the DNA damage, expression of heat shock protein 70 (Hsp70) and
      cell proliferation of human lens epithelial cells (hLEC) after exposure to the
      1.8 GHz radiofrequency field (RF) of a global system for mobile communications
      (GSM). An Xc-1800 RF exposure system was used to employ a GSM signal at 1.8 GHz
      (217 Hz amplitude-modulated) with the output power in the specific absorption
      rate (SAR) of 1, 2 and 3 W/kg. After 2 h exposure to RF, the DNA damage of hLEC
      was accessed by comet assay at five different incubation times: 0, 30, 60, 120
      and 240 min, respectively. Western blot and RT-PCR were used to determine the
      expression of Hsp70 in hLECs after RF exposure. The proliferation rate of cells
      was evaluated by bromodeoxyuridine incorporation on days 0, 1 and 4 after
      exposure. The results show that the difference of DNA-breaks between the exposed
      and sham-exposed (control) groups induced by 1 and 2 W/kg irradiation were not
      significant at any incubation time point (P > 0.05). The DNA damage caused by 3
      W/kg irradiation was significantly increased at the times of 0 and 30 min after
      exposure (P < 0.05), a phenomenon that could not be seen at the time points of
      60, 120 or 240 min (P > 0.05). Detectable mRNA as well as protein expression of
      Hsp70 was found in all groups. Exposure at SARs of 2 and 3 W/kg for 2 h exhibited
      significantly increased Hsp70 protein expression (P < 0.05), while no change in
      Hsp70 mRNA expression could be found in any of the groups (P > 0.05). No
      difference of the cell proliferation rate between the sham-exposed and exposed
      cells was found at any exposure dose tested (P > 0.05). The results indicate that
      exposure to non-thermal dosages of RF for wireless communications can induce no
      or repairable DNA damage and the increased Hsp70 protein expression in hLECs
      occurred without change in the cell proliferation rate. The non-thermal stress
      response of Hsp70 protein increase to RF exposure might be involved in protecting
      hLEC from DNA damage and maintaining the cellular capacity for proliferation.

PMID- 17011594
TI  - Deficiency of cell cycle checkpoints and DNA repair system predispose individuals
      to esophageal cancer.
AB  - Cell cycle checkpoints and DNA repair capacity are critical for the maintenance
      of genome integrity. We hypothesized that, in comparison to healthy controls,
      esophageal cancer patients might have a higher frequency of deficiencies in cell
      cycle checkpoints and/or DNA repair system. Using flow cytometry and comet assay,
      we assessed the gamma-radiation-induced S phase and G2-M phase accumulation, and
      benzo(a)pyrene-diol-epoxide (BPDE)- and gamma-radiation-induced DNA damage, in
      peripheral blood lymphocytes of 99 newly diagnosed esophageal cancer patients and
      112 age-, gender-, and ethnicity-matched healthy controls. The mean gamma
      radiation-induced cell accumulation at G2-M phase was significantly lower in
      esophageal cancer patients than the control subjects (case versus control:
      5.27%+/-5.11% versus. 7.06%+/-5.04%, P = 0.013). The less G2-M phase cell
      accumulation resulted in a significant increased risk for esophageal cancer with
      an odds ratio of 2.08 (95% confidence interval 1.15-3.77). After normalization to
      baseline S fraction, the radiation-induced increment in the 4N/2N ratio was also
      significantly lower in esophageal cancer patients than in controls (case versus
      control: 0.76% versus 1.04%, P = 0.0039). The less increment in the radiation
      induced 4N/2N ratio was associated with 2.24(95% confidence interval 1.22-4.11)
      fold increase of esophageal cancer risk. We also compared the mutagen-induced DNA
      damage level among individuals with different S or G2-M phase cell accumulation.
      We found that the less G2-M phase accumulation was associated with both high BPDE
      induced and gamma-radiation-induced DNA damage in the healthy controls (P for
      trend = 0.023 and 0.015, respectively). Similar pattern was observed for S phase
      accumulation (P for trend = 0.033 and 0.022, respectively). However, such
      association was not seen in esophageal cancer patients. This study provides the
      first molecular epidemiologic evidence linking increased esophageal cancer risk
      with defects in cell-cycle checkpoints and DNA repair capacity.

PMID- 17011596
TI  - In vitro galantamine-memantine co-application: mechanism of beneficial action.
AB  - Several drugs are in clinical use for symptomatic treatment of Alzheimer's
      disease patients. Since Alzheimer's disease is known to be associated with down
      regulation of the cholinergic and N-methyl-D-aspartate (NMDA) systems, most of
      these drugs inhibit acetylcholinesterase, potentiate the activity of nicotinic
      acetylcholine receptors (nAChRs), or modulate NMDA receptors. Galantamine is an
      anticholinesterase and allosterically potentiates the activity of the nicotinic
      receptors. We have recently found that galantamine potentiates the activity of
      NMDA receptors as well. Memantine is unique in that it inhibits the NMDA
      receptors. We have developed a hypothesis that combining galantamine and
      memantine will be more effective for improving the patient's conditions than
      monotherapy with either drug. Patch clamp and intracellular Ca(2+) imaging
      experiments using rat cortical and hippocampal neurons clearly provided the in
      vitro bases for our hypothesis. Memantine blocked the extrasynaptic NMDA receptor
      100 times more potently than the synaptic NMDA receptor at negative membrane
      potentials and the block of both types of NMDA receptors was attenuated with
      depolarization. However, galantamine potentiation of the NMDA receptors was not
      voltage dependent. Thus, co-application of memantine with galantamine prevented
      the galantamine potentiation and the activation of extrasynaptic NMDA receptors,
      but membrane depolarization revealed the galantamine potentiation. Therefore,
      cell death is expected to be prevented by memantine near the resting potential
      while the NMDA-mediated synaptic transmission, which is down-regulated in the
      patients, is maintained and potentiated by galantamine. These results provide in
      vitro bases for the beneficial actions of galantamine and memantine combinations.

PMID- 17011597
TI  - Metabotropic glutamate subtype 5 receptors modulate fear-conditioning induced
      enhancement of prepulse inhibition in rats.
AB  - Non-startling acoustic events presented shortly before an intense startling sound
      can inhibit the acoustic startle reflex. This phenomenon is called prepulse
      inhibition (PPI), and is widely used as a model of sensorimotor gating. The
      present study investigated whether PPI can be modulated by fear conditioning,
      whose acquisition can be blocked by the specific antagonist of metabotropic
      glutamate receptors subtype 5 (mGluR5), 2-methyl-6-(phenylethynyl)-pyridine
      (MPEP). The results show that a gap embedded in otherwise continuous noise
      sounds, which were delivered by two spatially separated loudspeakers, could
      inhibit the startle reflex induced by an intense sound that was presented 50 ms
      after the gap. The inhibitory effect depended on the duration of the gap, and was
      enhanced by fear conditioning that was introduced by temporally pairing the gap
      with footshock. Intraperitoneal injection of MPEP (0.5 or 5mg/kg) 30 min before
      fear conditioning blocked the enhancing effect of fear conditioning on PPI, but
      did not affect either the baseline startle magnitude or PPI if no fear
      conditioning was introduced. These results indicate that PPI is enhanced when the
      prepulse signifies an aversive event after fear conditioning. Also, mGlu5Rs play
      a role in preserving the fear-conditioning-induced enhancement of PPI.

PMID- 17011599
TI  - Functional differences between NPFF1 and NPFF2 receptor coupling: high intrinsic
      activities of RFamide-related peptides on stimulation of [35S]GTPgammaS binding.
AB  - By using an optimized [(35)S]GTPgammaS binding assay, the functional activities
      (potency and efficacy) of peptides belonging to three members of the RFamide
      family; Neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP) and 26RFamide,
      were investigated on NPFF(1) and NPFF(2) receptors stably expressed in Chinese
      Hamster Ovary (CHO) cells. Despite their large differences in affinity and
      selectivity, all analogues tested behaved as agonists toward NPFF(1) and NPFF(2)
      receptors. High NaCl concentration in the assay strongly increased the efficacy
      toward NPFF(2) receptors and augmented differences among agonists. In low sodium
      conditions, whereas the potencies of agonists correlated with their affinities
      for NPFF(1) receptors, NPFF(2) receptors exhibited an extraordinary activity
      since all compounds tested displayed EC(50) values of GTPgammaS binding lower
      than their K(I) values. Comparisons of functional values between NPFF(1) and
      NPFF(2) receptors revealed unexpected potent selective NPFF(2) agonists
      especially for the PLRFamide and the VGRFamide sequences. By using blocker
      peptides, we also show that Galpha(i3) and Galpha(s) are the main transducers of
      NPFF(1) receptors while NPFF(2) are probably coupled with Galpha(i2), Galpha(i3),
      Galpha(o) and Galpha(s) proteins. Our data indicate that NPPF(1) and NPFF(2)
      receptors are differently coupled to G proteins in CHO cells.

PMID- 17011598
TI  - Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats.
AB  - Recent studies have shown that activation of the cannabinoid CB(1) receptor by
      synthetic agonists, and pharmacological elevation of endocannabinoid levels,
      suppress hyperalgesia and allodynia in animal models of neuropathic pain.
      However, the concentrations of endocannabinoids in the nervous tissues involved
      in pain transmission during neuropathic pain have never been measured. Here we
      have determined the levels of anandamide and 2-arachidonoylglycerol (2-AG), as
      well as of the analgesic anandamide congener, palmitoylethanolamide (PEA), in
      three brain areas involved in nociception, i.e. the dorsal raphe (DR),
      periaqueductal grey (PAG) and rostral ventral medulla (RVM), as well as in the
      spinal cord (SC), following chronic constriction injury (CCI) of the sciatic
      nerve in the rat, in comparison with sham-operated rats. After 3 days from CCI,
      anandamide or 2-AG levels were significantly enhanced only in the SC or PAG,
      respectively. After 7 days from CCI, when thermal hyperalgesia and mechanical
      allodynia are maximal, a strong (1.3-3-fold) increase of both anandamide and 2-AG
      levels was observed in the PAG, RVM and SC. At this time point, anandamide, but
      not 2-AG, levels were also enhanced in the DR. PEA levels were significantly
      decreased in the SC after 3 days, and in the DR and RVM after 7 days from CCI.
      These data indicate that anandamide and 2-AG, operating at both spinal and supra
      spinal levels, are up-regulated during CCI of the sciatic nerve, possibly to
      inhibit pain. Yet to be developed substances that inhibit both endocannabinoid
      and PEA inactivation might be useful for the treatment of neuropathic pain.

PMID- 17011600
TI  - Presynaptic modulation of parallel fibre signalling to Bergmann glia.
AB  - Transmission at the parallel fibre-Purkinje neurone synapse of the cerebellum can
      be depressed by a number of presynaptic receptors: endocannabinoid (CB1),
      metabotropic glutamate (mGluR4), adenosine (A1) and GABA (GABA(B)), which have
      been implicated in both short- and long-term synaptic plasticity. Stimulation of
      parallel fibres also activates glutamate receptors and transporters on the
      Bergmann glial cell that forms a sheath around the synapse. The resulting glial
      extrasynaptic currents (ESC) exhibit short- and long-term plasticity, which
      differs from the plasticity of adjacent synapses. This functional independence
      could arise from differential modulation of presynaptic release sites targeted to
      synapses or glia, but the sensitivity of glial ESC to these inhibitory pathways
      is unknown. Here I show that all four presynaptic receptors depress parallel
      fibre-Bergmann glial cell signalling with similar potency to synaptic
      transmission. Depression of glial ESC is accompanied by a decrease in paired
      pulse ratio. However, application of receptor antagonists had no effect on ESC
      amplitude, indicating that tonic activation of these pathways does not occur, and
      antagonists failed to block the activity-dependent depression of glial ESC
      observed during tetanic or low frequency stimulation. These data suggest that
      modulation of presynaptic glutamate release does not underlie glial plasticity.

PMID- 17011601
TI  - Semantic associations, lateralized frontal function, and context maintenance in
      schizotypy.
AB  - Symptom heterogeneity within conventional diagnostic groups is fostering a
      growing focus on narrower symptom profiles to identify psychological and
      biological mechanisms in psychopathology. Positive symptoms of schizophrenia are
      associated with context maintenance deficits, which in turn have been linked to
      frontal-lobe function. Frontal- and temporal-lobe brain dysfunction is also well
      documented in schizophrenia. The present study (N=36) examined how context and
      memory deficits are associated with subclinical symptoms in schizotypy by
      investigating the relationship between symptom reports, neuropsychological
      performance, and several facets of recognition memory. Context maintenance was
      probed via lures suggested by presented verbal material. Frontal brain function
      and positive symptom schizotypy predicted accuracy for lures, whereas posterior
      brain function and low positive affect predicted accuracy for distracters. This
      pattern of findings establishes continuity in disruption of context maintenance
      in clinical and subclinical populations.

PMID- 17011602
TI  - Trends in rural and urban differentials in incidence rates for ruptured
      appendicitis under the National Health Insurance in Taiwan.
AB  - OBJECTIVES: Rural-urban disparities in health remain a major focus of concern.
      This population-based study examined the performance of Taiwan's universal
      healthcare system in reducing rural-urban disparities in health, through better
      accessibility. Changes in the rates of ruptured appendicitis were compared
      between residents of remote and non-remote areas in Taiwan, under the National
      Health Insurance (NHI) programme. METHODS: We identified all 128,930 patients
      undergoing appendectomy in Taiwan between 1996 and 2001. The NHI inpatient files,
      enrolment files, major disease files, hospital registry and the household
      registry were linked to provide comprehensive individual and hospital
      information. Probit regression analyses were used to obtain adjusted estimates.
      RESULTS: During the first 3 years, although the differences between the remote
      and non-remote areas were apparent, they were seen to be narrowing. This downward
      trend continued, and, since 1999, few discernible differences have been observed.
      After adjusting for individual and hospital characteristics, over time, the
      ruptured appendix rate among remote area residents was seen to be decreasing
      significantly faster (1.1%) than among non-remote area residents. More
      specifically, the children showed a substantially steeper narrowing trend (3.3%)
      in rural-urban disparities, than did adults. CONCLUSIONS: Our findings have shown
      a significant narrowing of health disparities between remote and non-remote
      populations, resulting from free access to care and more healthcare provision in
      remote areas under the NHI programme; particular success has been observed in
      rural children. Although certain disparities still exist, Taiwan's universal
      healthcare system has effectively reduced rural-urban disparities in access to
      care and in ultimate health outcomes.

PMID- 17011603
TI  - Regional differences in transdermal penetration of fentanyl through equine skin.
AB  - The rate and regional differences for the penetration of fentanyl through equine
      skin was investigated in vitro using a commercial transdermal therapeutic system
      (TTS) or 'patch'. Skin collected from the thorax, groin and leg (dorsal
      metacarpal) regions of five horses was placed in diffusion cells and a fentanyl
      TTS applied to each skin sample. Drug penetration through each skin sample over
      48 h measured using high performance liquid chromatography (HPLC). Cumulative
      penetration (microg/cm2) was plotted against time (h) and used to regress the
      steady state flux (microg/cm2/h) of fentanyl through each skin site. Results
      showed similar fluxes for both the thorax (2.32+/-0.17 microg/cm2/h and groin
      (2.21+/-0.11 (microg/cm2/h) regions, but significantly lower flux (P=<0.05) for
      the leg region (1.56+/-0.120 microg/cm2/h. Interestingly, there was a
      significantly longer lag time for the penetration of fentanyl through the groin
      region (7.87+/-0.51 h) compared to the other two sites (5.66+/-0.97 h and 5.75+/
      0.43 h for the thorax and leg regions respectively). The results suggest that a
      fentanyl TTS applied to the leg region may have a small but significantly lower
      amount of fentanyl available systemically, compared to patches applied to the
      thorax or groin regions, which may affect the level of analgesia subsequently
      achieved in the horse.

PMID- 17011604
TI  - Activity of matrix metalloproteinase-2 (MMP-2) in canine oronasal tumors.
AB  - Activity of matrix metalloprotease-2 (MMP-2) and the expression of its related
      molecules were examined in spontaneous canine oronasal tumors. Tissue samples
      from melanoma and squamous cell carcinoma possessed higher MMP-2 activity, as
      shown in gelatin zymography, in comparison with acanthomatous epulis and nasal
      adenocarcinoma. Regional lymph node invasion and distant metastases were more
      frequently observed in the MMP-2 positive cases. There were no significant
      differences by RT-PCR examination in the expression of the genes encoding MMP-2,
      MT1-MMP and TIMP-2 among the tumor histological types. However, the MMP-2/TIMP-2
      ratio showed a significantly higher level of the genes in the malignant oral
      melanoma and squamous cell carcinoma. The MMP-2/TIMP-2 ratio was also positively
      correlated with MMP-2 activity in gelatin zymography. These results indicate that
      the MMP-2/TIMP-2 ratio may be of value in evaluating the prognosis in canine
      oronasal cavity tumors.

PMID- 17011605
TI  - Neuroparacoccidioidomycosis: analysis of 13 cases observed in an endemic area in
      Brazil.
AB  - The epidemiological, clinical and laboratory features of 13 cases of
      neuroparacoccidioidomycosis (NPCM) were analysed. All patients were men, with a
      mean age of 41.6 years. The lungs were involved in 11 cases (84.6%) and only two
      cases had mycosis limited to the central nervous system. Co-morbidity was
      observed in four patients (malignant neoplasm in three and diabetes mellitus in
      one). The most frequent neurological manifestations were paresis (eight cases),
      headache (five cases) and gait disturbance (four cases). Neuroimaging diagnosis
      showed a predominance of multiple round lesions with ring enhancement following
      contrast medium injection. Lesions were seen in the brain hemispheres (nine
      cases), thalamus (nine cases), cerebellum (four cases), brainstem (four cases)
      and spinal cord (four cases). Most cases responded well to therapy. Lesions with
      enhancement following contrast medium injection persisted in four patients for a
      period of 6 months to 8 years. These findings emphasize the importance of
      considering NPCM in the differential diagnosis of brain and spinal cord lesions
      in endemic areas of paracoccidioidomycosis.

PMID- 17011606
TI  - Placental transport of brevetoxin-3 in CD-1 mice.
AB  - The purpose of this study was to examine the distribution of brevetoxin-3
      administered to pregnant dams and to determine the extent of placental transport
      to fetuses. Twenty-nine pregnant CD-1 mice were administered (3)H-brevetoxin-3 (
      approximately 1.3 microCi/animal; approximately 2.8 microg compound/kg) by
      intratracheal instillation on one of gestational days 15-18. Groups of four or
      five dams were killed at selected times through 48 h post-dosing. Four pregnant
      dams were administered (3)H-brevetoxin-3 on gestational day 15 or 16 via osmotic
      minipump to provide continuous delivery of compound ( approximately 0.13 microCi,
      7.5 ng compound/day) over a 72-h period. Then the dams and fetuses were killed.
      Brevetoxin-associated radioactivity was detected in placentas and fetuses within
      0.5h of intratracheal administration. Concentrations of brevetoxin equivalents in
      fetuses were approximately 0.3 ng/g throughout the 48-h post-dosing, resulting in
      a calculated dose to fetuses of 19 ng/gh. Following brevetoxin infusion,
      concentration of brevetoxin equivalents in fetuses was 0.1 ng/g, lower than that
      present in most maternal tissues. Results demonstrated placental transport of
      brevetoxin or its metabolites following maternal acute exposure and repeated low
      dose exposure. The consequences of these findings for pregnant women exposed to
      brevetoxins by inhalation or ingestion remain to be determined.

PMID- 17011608
TI  - Detection and estimation of potentially toxic cyanobacteria in raw water at the
      drinking water treatment plant by in vivo fluorescence method.
AB  - In vivo fluorescence methods have been accepted as a quick, simple, and useful
      tool for quantification of phytoplankton organisms. In this paper, we present a
      case study in which fluorescence methods were employed for the selective
      detection of potentially toxic cyanobacteria in raw water at the drinking water
      treatment plant. The occurrence of cyanobacteria in the drinking water reservoir
      and in raw water was monitored by phycocyanin fluorescence measurements and by
      standard methods for phytoplankton quantification (cell counts, chlorophyll a). A
      special attention was paid to the most critical parts of the season -- spring
      recruitment of cyanobacteria from sediment to water column and autumn bloom
      collapse. All methods showed similar patterns within the season. Phycocyanin
      fluorescence was found to be a simple and sensitive indicator of cyanobacteria in
      water and can serve as a tool that can provide an early warning about the
      presence of potentially toxic cyanobacterial metabolites in water.

PMID- 17011607
TI  - Information in the first spike, the order of spikes, and the number of spikes
      provided by neurons in the inferior temporal visual cortex.
AB  - Information theoretic analyses showed that for single inferior temporal neurons
      and neuronal populations, more information was encoded in 20 or more ms by all
      the spikes available than just by the first spike in the same time window about
      which of 20 objects or faces was shown. Further, the temporal order in which the
      first spike arrived from different simultaneously recorded neurons did not encode
      more information than was present in the first spike or the spike counts. Thus
      information transmission in the inferior temporal cortex by the number of spikes
      in even short time windows is fast, and provides more information than only the
      first spike, or the spike order from different neurons.

PMID- 17011609
TI  - Cercopithecoid cervical vertebral morphology and implications for the presence of
      Theropithecus in early Pleistocene Europe.
AB  - While it is recognized that the overall configuration of the vertebral column, as
      well as the size and shape of individual vertebrae, differ within and between
      primate taxa, relatively little is known about the degree to which vertebral
      morphology reflects a phylogenetic signal or the degree to which vertebral
      elements can be used in accurate taxonomic classification. Isolated vertebrae are
      occasionally found in fossil assemblages, and proper taxonomic identification is
      necessary to make inferences about the animal's biology and place it in a broader
      phylogenetic and evolutionary context. Recently, three large primate cervical
      vertebrae (C3, C5, and C6) from Pirro Nord, Italy (early Pleistocene, late
      Villafranchian) were attributed to the genus Theropithecus based on size
      comparisons with extant cercopithecoid primates (Rook et al., 2004, J. Hum. Evol.
      47, 267-277). These fossils were suggested to indicate an early dispersal of this
      genus out of Africa around 1.6-1.3 Ma possibly co-incident with early Pleistocene
      dispersals of Homo. Because of the potential importance of these fossils for
      interpreting Theropithecus evolution and the relatively few morphological data on
      primate cervical vertebral morphology, we examined the size and shape of cervical
      vertebrae in a large sample of extant cercopithecoid taxa (n=106). Specifically,
      we evaluated whether subfamily and genus level assignments can be made on the
      basis of isolated cervical elements. Discriminant analyses reveal that scaled
      shape variables are good discriminators of taxonomic affinity at the subfamily
      level but are poor discriminators at the genus level. Least-squares regressions
      show that raw linear dimensions of cervical vertebral morphology are good
      predictors of body mass in the extant sample. Our regression results produce a
      likely body mass estimate of 22-38 kg for the Pirro Nord cervical vertebrae.
      Based on these regression estimates, the poor ability to discriminate cervical
      vertebrae at the genus level, and paleoenvironmental reconstructions of Pirro
      Nord, it is unlikely that the Pirro Nord fossils can be confidently attributed to
      the genus Theropithecus. These findings have important implications for recent
      interpretations of the nature of Theropithecus dispersal out of Africa.

PMID- 17011610
TI  - Maximum likelihood mixture estimation to determine metal background values in
      estuarine and coastal sediments within the European Water Framework Directive.
AB  - Some of the recently derived European Directives, such as the Water Framework and
      Marine Strategy, have, as ultimate aims, to achieve concentrations of hazardous
      substances in the marine environment near background values. Hence, the
      determination of natural background levels, in marine sediments, is highly
      relevant. The present study proposes the use of the maximum likelihood mixture
      estimation (MLME) to determine regional background levels and upper threshold of
      metal concentration, with the Basque Country as a case study (with a data set of
      575 samples, from estuarine and littoral areas, including both intertidal and
      subtidal sediments). The heuristic procedure is applied with unimodal data
      distributions (Cd, Cr, Fe and Ni) and the mixture density estimations, based upon
      maximum likelihood, are carried out with polypopulational data distributions (As,
      Cu, Mn, Hg, Pb and Zn). The upper limits of the distribution are proposed, as the
      limits between 'High Status' and 'Good Status' (according to the Water Framework
      Directive terminology). The regional upper limits were 0.45 microg g(-1) for Cd,
      71 microg g(-1) for Cr, 53,542 microg g(-1) for Fe, 57 microg g(-1) for Ni, 24
      microg g(-1) for As, 64 microg g(-1) for Cu, 447 microg g(-1) for Mn, 0.27 microg
      g(-1) for Hg, 66 microg g(-1) for Pb, and 248 microg g(-1) for Zn. The results
      from this study can assist further in the determination of sediment reference
      conditions, to assess chemical status, within the above-mentioned directives;
      likewise, it will be studied as a useful methodology in determining regional
      metal backgrounds in other European countries.

PMID- 17011611
TI  - "Crystal clear"-sonographic assessment of gout and calcium pyrophosphate
      deposition disease.
AB  - OBJECTIVES: To date, high-resolution ultrasound (US) has not been fully exploited
      in the field of crystalline arthropathy. Both gout and calcium pyrophosphate
      deposition (CPPD) disease are significant diseases within the purview of the
      rheumatologist. The aim of this pictorial review was to present the principal
      findings in patients with crystal deposition in gout and CPPD. METHODS: US
      pictures were obtained from 60 consecutive patients, 34 with CPPD disease and 26
      with gout, whose diagnosis was confirmed by synovial fluid analysis. The US
      examinations were performed using the following US systems: Diasus (Dynamic
      Imaging, Livingstone, UK) and Logiq 9 (General Electric Medical Systems,
      Milwaukee, WI). RESULTS: Pictorial evidence of the principal US findings in gout
      includes monosodium urate (MSU) deposition on the surface of articular cartilage,
      various patterns within synovial fluid ranging from completely anechoic fluid to
      collections filled with aggregates of variable shape and echogenicity,
      microdeposition within tendons, and tophus formation. In CPPD, the hallmark US
      features include crystal deposition within articular cartilage, calcification of
      fibrocartilage, together with focal crystal deposition within tendons.
      CONCLUSION: US is an impressive imaging modality in crystalline arthropathy. The
      anatomical location of the crystal deposits, clearly depictable by US, allows
      differentiation between MSU and CPPD aggregates.

PMID- 17011612
TI  - Ankylosing spondylitis: a contemporary perspective on diagnosis and treatment.
AB  - OBJECTIVES: In recent years, great progress has been made in the development of
      diagnostic tools, therapeutic approaches, and validated outcome measures in the
      understanding of the pathogenesis of ankylosing spondylitis (AS). The purpose of
      this review was to summarize these developments. METHODS: We performed a PubMed
      search for the period 1978 to 2005, using the keyword, "ankylosing spondylitis,"
      resulting in a total of 4878 publications, including 778 reviews. Articles were
      then selected based on their discussion of recent diagnostic tools and new
      treatment approaches in the pathogenesis of AS, leading to a final total of 104
      articles. RESULTS: In recent years, there have been 2 major developments in the
      management of AS that make earlier diagnosis possible and offer the hope of
      alleviating pain and preventing structural changes that result in loss of
      function. These developments include the use of magnetic resonance imaging to
      visualize the inflammatory changes in the sacroiliac joint and the axial spine,
      and the demonstration that tumor necrosis factor blocking agents are highly
      efficacious in reducing spinal inflammation and possibly in slowing radiographic
      progression. CONCLUSIONS: There have been major advances in both the diagnostic
      tools and the therapeutic regimens available for patients with AS.

PMID- 17011613
TI  - Pitavastatin attenuates the upregulation of tissue factor in restraint-stressed
      mice.

PMID- 17011614
TI  - Idiopathic portal vein thrombosis and FVIII levels.

PMID- 17011615
TI  - Areas with benign morphologic and immunohistochemical features are associated
      with some uterine leiomyosarcomas.
AB  - The pathogenesis of uterine leiomyosarcomas (LMS) is poorly understood. It is
      unknown if these tumors arise de-novo or from pre-existing leiomyomata (LM) or
      atypical leiomyomata. In this study, we evaluated morphologic heterogeneity
      within uterine LMS to identify possible precursor lesions. We reviewed 11 cases
      of total hysterectomy in which the final diagnosis was LMS. All slides from the
      grossly recognized tumor were evaluated for the degree of atypia and mitotic
      counts within the leiomyosarcomas. The slides with the lowest and highest mitotic
      count were stained with monoclonal antibody to p53, MIB-1 and ER/PR. The number
      of cells stained was subjectively assessed to nearest 5%, with 1% for rare
      positive cells. Morphologically benign tumor areas were identified in 5 of the 11
      tumors. These areas showed <5 mitoses/10 HPF, with 1+ atypia in 4 cases and 1-2+
      atypia in 1 case. No necrosis was seen by definition. Immunostains could be done
      in 4 of these 5 cases. These morphologically benign areas showed a p53 expression
      of 1% in each of the 4 cases, with low MIB-1 (5 to 15%) and high ER/PR expression
      (ER: 50-100%, PR: 10-100%). Morphologically malignant areas had 13 to 31
      mitoses/10 HPF, 2+ to 3+ atypia, p53 expression of 70% to 100%, MIB-1 expression
      of 40% to 100%, ER expression of 1 to 100% and PR expression of 1 to 100%. The
      benign and malignant areas merged in all cases. Morphologic and
      immunohistochemical spectrum of changes from benign to malignant is seen in 50%
      of LMS. This raises the possibility of progression of some leiomyomata to LMS.

PMID- 17011616
TI  - The risk of persistent trophoblastic disease after hydatidiform mole classified
      by morphology and ploidy.
AB  - OBJECTIVE: Hydatidiform mole can be classified by histopathologic characteristics
      and by genetic constitutions and most complete moles are diploid, whereas most
      partial moles are triploid. We investigated the concordance between these two
      classifications, characterized moles with conflicting classifications, and
      compared the ability of the two classifications to discriminate between patients
      with and without a substantial risk of persistent trophoblastic disease. METHODS:
      294 cases of consecutively collected hydropic placentas clinically suspected of
      hydatidiform mole made the basis of this retrospective study. We determined the
      ploidy and reviewed the original histopathologic material in all cases. Data on
      possible chemotherapy were collected for each patient. RESULTS: 270 of the
      conceptuses were histopathologically classified as hydatidiform mole. Among the
      24 conceptuses classified as non-molar miscarriage, 20 were triploids, 2 were
      diploid androgenetic and 2 were diploid biparental. In 23% of the conceptuses,
      the histopathologic and genetic classifications were conflicting. 5% of the
      patients with hydropic placentas classified as partial mole encountered
      persistent trophoblastic disease; however, the genome was diploid in all these
      moles. None of 131 patients with a triploid hydropic gestation encountered
      persistent trophoblastic disease. CONCLUSION: As full concordance between the
      histopathologic and the genetic classifications was not found, we believe that
      features beyond the genetic constitution influence the development of morphologic
      features in hydatidiform moles. We recommend that gestations suspected of
      hydatidiform mole are subjected to histopathologic examination. If hydatidiform
      change and trophoblastic hyperplasia are identified, the ploidy should be used to
      identify patients with a high risk of persistent trophoblastic disease.

PMID- 17011617
TI  - Conditioned place preference induced by morphine and morphine-6-glucuronide in
      mice.
AB  - Morphine-6-glucuronide (M6G), an active metabolite of morphine has been shown to
      produce analgesia and fewer side effects than morphine, and the introduction of
      M6G as a new drug for treatment of postoperative pain is planned in 2007.
      Following morphine intake in humans, the metabolites morphine-3-glucuronide (M3G)
      and M6G are present in substantial concentrations and for longer periods than the
      parent drug. The possible reward effects of the morphine glucuronides have
      previously not been well studied. In the present study, conditioned place
      preference (CPP) was recorded after conditioning with subcutaneous injections of
      5, 10, 20, 30 or 50 micromol/kg morphine or M6G, or 240 or 500 micromol/kg M3G in
      C57BL/6J-Bom mice, using a biased two compartment ("closed" and "open")
      counterbalanced paradigm. CPP was induced after treatment with both morphine and
      M6G with dose dependent increase up to 30 micromol/kg after treatment in the
      "closed" compartment. No dose response was observed in the "open" compartment,
      with maximal CPP after 10 micromol/kg morphine or M6G. M3G caused a tendency of
      condition place aversion (CPA), although not statistically significant. In the
      present study morphine and M6G demonstrated comparable reward effects, at doses
      that differed depending on which compartment the mice were conditioned in. M3G
      showed a tendency to exhibit aversive properties.

PMID- 17011618
TI  - Step count recommendations for children based on body fat.
AB  - OBJECTIVE: Current recommendations for pedometer-determined physical activity in
      children (boys, 15,000 steps/day; girls, 12,000 steps/day) were based on the
      association between weekday step counts and body mass index. The objective of
      this study was to develop new targets using both weekday and weekend step counts
      with percentage body fat (%BF) as the criterion reference. METHOD: The %BF of 969
      New Zealand European, Polynesian, and Asian children (515 male, 454 female) aged
      5-12 years was measured in 2004 using hand-to-foot bioelectrical impedance
      analysis. Weekday and weekend step counts, assessed using sealed multi-day-memory
      pedometers over 5 days, were combined into a scaled mean step count. The
      contrasting groups method for determining criterion-referenced cut-off points was
      used to establish the optimal step count values for predicting overweight
      (%BF>85th percentile) and non-overweight (%BF<85th percentile). RESULTS:
      Overweight children had significantly lower mean step counts (14,238+/-3343,
      boys; 12,555+/-3169, girls) than non-overweight children (16,106+/-3208, boys;
      14,176+/-2728, girls). Optimal step count cut-off points were 16,000 steps/day
      for boys and 13,000 steps/day for girls. CONCLUSION: Step count targets for
      reducing the risk of excess body fat in children are 1000 steps/day higher than
      existing BMI-referenced guidelines.

PMID- 17011619
TI  - Modulating bone cells response onto starch-based biomaterials by surface plasma
      treatment and protein adsorption.
AB  - The effect of oxygen-based radio frequency glow discharge (rfGD) on the surface
      of different starch-based biomaterials (SBB) and the influence of proteins
      adsorption on modulating bone-cells behavior was studied. Bovine serum albumin,
      fibronectin and vitronectin were used in single and complex protein systems. RfGD
      treated surfaces showed to increase in hydrophilicity and surface energy when
      compared to non-modified SBB. Biodegradable polymeric blends of cornstarch with
      cellulose acetate (SCA; 50/50wt%), ethylene vinyl alcohol (SEVA-C; 50/50wt%) and
      polycaprolactone (SPCL; 30/70wt%) were studied. SCA and SCA reinforced with 10%
      hydroxyapatite (HA) showed the highest degree of modification as result of the
      rfGD treatment. Protein and control solutions were used to incubate with the
      characterized SBB and, following this, MG63 osteoblast-like osteosarcoma cells
      were seeded over the surfaces. Cell adhesion and proliferation onto SCA was found
      to be enhanced for non-treated surfaces and on SCA+10%HA no alteration was
      brought up by the plasma modification. Onto SCA surfaces, BSA, FN and VN single
      solutions improved cell adhesion, and this same effect was found upscaled for
      ternary systems. In addition, plasma treated SEVA-C directed an increase in both
      adhesion and proliferation comparing to non-treated surfaces. Even though
      adhesion onto treated and untreated SPCL was quite similar, plasma modification
      clearly promoted MG63 cells proliferation. Regarding MG63 cells morphology it was
      shown that onto SEVA-C surfaces the variation of cell shape was primarily defined
      by the protein system, while onto SPCL it was mainly affected by the plasma
      treatment.

PMID- 17011621
TI  - Allergenicity of airborne cyanobacteria Phormidium fragile and Nostoc muscorum.
AB  - In recent times, airborne microorganisms and their constituents have become
      prominent safety and health concern. Ongoing climatic changes coupled with
      unwarranted human activities have significantly deteriorated the ambient air
      quality. In certain environments, airborne algae contribute significantly to the
      total biological load of the atmosphere, hitherto dominated by bacteria and
      fungi. Present study was aimed to investigate the allergenic potency of two
      frequent viable algal forms i.e., Phormidium fragile and Nostoc muscorum found in
      the atmosphere of Varanasi City, India. To test the allergenic potency, crude
      extracts of these strains were subjected to intra-dermal allergy test and
      subsequent leukocyte counts, which revealed their allergenic nature. Both the
      species varied in their allergenic potency. N. muscorum appeared to be more
      allergenic than P. fragile. However, when the allergens were mixed in equal
      amounts, the severity of allergenicity increased significantly. A limited pattern
      of cross-reactivity between the species was also evident.

PMID- 17011620
TI  - Effects of metals and detergents on biotransformation and detoxification enzymes
      of leaping mullet (Liza saliens).
AB  - In this study, feral leaping mullet (Liza saliens) liver microsomal 7
      ethoxyresorufin O-deethylase (EROD), and cytosolic glutathione S-transferases
      (GSTs) activities were investigated using 7-ethoxyresorufin, 1-chloro-2,4
      dinitrobenzene (CDNB), and ethacrynic acid (EA) as substrates, respectively. The
      average EROD activity was found as 1139+/-175 pmol resorufin/min/mg protein. The
      average GST activities towards CDNB and EA were found as 1364+/-41 and 140+/-19
      nmol/min/mg protein, respectively. We have, then, investigated the in vitro
      effects of some metals and detergents on CYP1A and GST activities in leaping
      mullet liver. Leaping mullet liver microsomal EROD activity was significantly
      inhibited by Hg (0.1 mM), Ni (0.1 mM), Cd (0.1 mM), Cu (0.1 mM), Zn (0.1 mM), Sb
      (0.1 mM), Fe2+ (1 mM), Co (1 mM), Al (1 mM), and Fe3+ (1 mM), with the percent
      inhibition of 80, 80, 77, 75, 70, 69, 56, 53, 46, and 44, respectively.
      Similarly, conjugation of CDNB catalyzed by GST was inhibited significantly to
      lesser extend by Hg (0.1mM), Sb (0.1 mM), Cd (0.1 mM), Cu (0.1 mM), Zn (0.1 mM),
      Fe3+ (1 mM), Co (1 mM), and Fe2+ (1 mM), with the percent inhibition of 70, 69,
      65, 61, 54, 51, 47, and 43, respectively. The degrees of inhibition observed on
      GST catalyzed EA conjugation by Hg (0.1 mM), Cd (0.1 mM), Sb (0.1 mM), Cu (0.1
      mM), and Zn (0.1 mM) were 86, 78, 69, 51, and 42, respectively. In addition to
      metals, the effect of various detergents on leaping mullet liver EROD, GST-CDNB,
      and GST-EA activities were studied. It was found that ionic detergents strongly
      inhibited the EROD activity, whereas much less inhibitions were observed with GST
      catalyzed activities. Therefore, the CYP1A inhibition potencies of metals and
      detergents suggest that their contribution to the overall CYP1A induction in
      polycyclic aromatic hydrocarbons contaminated environmental samples has to be
      taken into account for better interpretation of environmental studies.

PMID- 17011622
TI  - A pilot study to assess residential endotoxin and blood IgE in a group of
      pregnant women from Trujillo, Peru.
AB  - OBJECTIVE: This November 2003 pilot study investigates the correlation between
      serum IgE and residential endotoxin levels from a group of 18 pregnant women
      living in Trujillo, Peru, and investigates the impact of the demographic and
      lifestyle factors of this group on the IgE and endotoxin levels measured.
      METHODS: Serum samples were collected from 19 subjects and analyzed for IgE. Dust
      samples were collected from the mattresses of 18 subjects and measured for
      endotoxin levels. A questionnaire was used to obtain demographic, socioeconomic,
      and lifestyle information for each subject. RESULTS: Geometric means for IgE and
      endotoxin were 246.8 (GSD=4.3, n=19) IU/mL and 66.5 EU/mg (GSD=1.7, n=18),
      respectively. Log-transformed IgE and endotoxin were not correlated (R2=0.02;
      p=0.60). CONCLUSIONS: Residential endotoxin and serum IgE were not correlated in
      this group. Potential selection bias and sample size are major limitations of the
      study. However, 74% (14/19) of the subjects in this study had an IgE over 100
      IU/mL, a level generally considered elevated.

PMID- 17011623
TI  - Accumulation features of organochlorine pesticides and heavy metals in fish from
      high mountain lakes and Lhasa River in the Tibetan Plateau.
AB  - Organochlorine pesticides and heavy metals were analyzed in fish from remote
      mountain lakes and Lhasa River in Tibetan Plateau. Concentrations of summation
      operatorHCH, summation operatorDDT and HCB in fish muscles were in the range of
      0.13-2.6 ng/g, 0.78-23 ng/g, 0.31-3.2 ng/g based on wet weight, respectively.
      Heavy metals were routinely found with different levels in fish. The Cu and Zn
      levels were relatively high with the maximum concentrations reaching 2.0 and 6.9
      microg/g, respectively. Accumulation of OCPs and heavy metals are quite different
      in tissues and organs. Gill seems to accumulate more OCPs due to absorption by
      its larger surface per tissue. Heavy metal levels were generally high in liver,
      eggs and gill, and low in brain and muscle. Results from this study demonstrate
      that the Tibetan Plateau functions as a regional contaminant convergence zone by
      long-range atmospheric transport and orographic cold trapping.

PMID- 17011624
TI  - Cross-linking of MHC class II molecules interferes with phorbol 12,13-dibutyrate
      induced differentiation of resting B cells by inhibiting Rac-associated ROS
      dependent ERK/p38 MAP kinase pathways leading to NF-kappaB activation.
AB  - In addition to their essential role in antigen presentation, major
      histocompatibility complex (MHC) class II molecules have been described as the
      receptor associated with signal transduction regulating B-cell function. In
      previous experiments, we found that cross-linking of MHC class II molecules with
      corresponding anti-MHC class II antibodies inhibited NF-kappaB-activated
      signaling pathways associated with the proliferation and differentiation of the
      LPS-stimulated primary and resting B-cell line, 38B9. We also found that exposure
      to the anti-MHC class II antibody reduced the production of ROS, which function
      as secondary signal transducers, in the phorbol 12,13-dibutyrate (PDBU)-treated
      (but not in the LPS-treated) resting B-cell line. In this study, we investigated
      the molecular mechanisms in the ROS-associated signaling pathway leading to PDBU
      induced NF-kappaB activation that results in B-cell differentiation and
      speculated that the signaling pathway was inhibited by exposure to the anti-MHC
      class II antibody. We also found that this inhibition was mediated through down
      regulation of the activated Rac/ROS-associated ERK/p38 MAPK signaling pathway in
      PDBU-treated 38B9 cells. Collectively, these findings suggest that ROS-associated
      molecules are involved in MHC class II-associated negative signal transduction in
      resting B cells.

PMID- 17011625
TI  - Compensation of endogenous IgG mediated inhibition of antibody-dependent cellular
      cytotoxicity by glyco-engineering of therapeutic antibodies.
AB  - A major limitation to the application of therapeutic IgG antibodies (Abs) is
      their reduced in vivo efficacy compared to their high efficacy as measured in
      vitro. Recently, Preithner et al. showed that the high amount of endogenous serum
      IgG impairs the antibody-dependent cellular cytotoxicity effector function (ADCC)
      of therapeutic Abs in vivo by competing for binding to Fcgamma-RIII on the
      effector cells. Modification of the glycosylation moieties attached to the Fc
      part of the Ab, e.g. de-fucosylation, has been shown to increase ADCC activity.
      We here show that the ADCC activity of a fucose-deficient, moss-produced
      therapeutic IgG is not impaired by normal human serum. The increased ADCC
      activity of the fucose-deficient Ab variant even in the presence of high
      endogenous IgG indicates that glyco-engineering of Abs may translate into
      improved clinical efficacy. Noteworthy, moss production of glyco-modified Abs
      should be applicable to a broad variety of therapeutic Abs currently in use
      indicative for the potential of this technology platform.

PMID- 17011626
TI  - Phenotypic analysis of the ccp1Delta and ccp1Delta-ccp1W191F mutant strains of
      Saccharomyces cerevisiae indicates that cytochrome c peroxidase functions in
      oxidative-stress signaling.
AB  - Yeast cytochrome c peroxidase (CCP) efficiently catalyzes the reduction of
      H(2)O(2) to H(2)O by ferrocytochrome c in vitro. The physiological function of
      CCP, a heme peroxidase that is targeted to the mitochondrial intermembrane space
      of Saccharomyces cerevisiae, is not known. CCP1-null-mutant cells in the W303-1B
      genetic background (ccp1Delta) grew as well as wild-type cells with glucose,
      ethanol, glycerol or lactate as carbon sources but with a shorter initial
      doubling time. Monitoring growth over 10 days demonstrated that CCP1 does not
      enhance mitochondrial function in unstressed cells. No role for CCP1 was apparent
      in cells exposed to heat stress under aerobic or anaerobic conditions. However,
      the detoxification function of CCP protected respiring mitochondria when cells
      were challenged with H(2)O(2). Transformation of ccp1Delta with ccp1(W191F),
      which encodes the CCP(W191F) mutant enzyme lacking CCP activity, significantly
      increased the sensitivity to H(2)O(2) of exponential-phase fermenting cells. In
      contrast, stationary-phase (7-day) ccp1Delta-ccp1(W191F) exhibited wild-type
      tolerance to H(2)O(2), which exceeded that of ccp1Delta. Challenge with H(2)O(2)
      caused increased CCP, superoxide dismutase and catalase antioxidant enzyme
      activities (but not glutathione reductase activity) in exponentially growing
      cells and decreased antioxidant activities in stationary-phase cells. Although
      unstressed stationary-phase ccp1Delta exhibited the highest catalase and
      glutathione reductase activities, a greater loss of these antioxidant activities
      was observed on H(2)O(2) exposure in ccp1Delta than in ccp1Delta-ccp1(W191F) and
      wild-type cells. The phenotypic differences reported here between the ccp1Delta
      and ccp1Delta-ccp1(W191F) strains lacking CCP activity provide strong evidence
      that CCP has separate antioxidant and signaling functions in yeast.

PMID- 17011628
TI  - Influence of chelators and iron ions on the production and degradation of H2O2 by
      beta-amyloid-copper complexes.
AB  - beta-Amyloid peptide (Abeta) 1-42, involved in the pathogenesis of Alzheimer's
      disease, binds copper ions to form AbetaxCu(n) complexes that are able to
      generate H(2)O(2) in the presence of a reductant and O(2). The production of
      H(2)O(2) can be stopped with chelators. More reactive than H(2)O(2) itself,
      hydroxyl radicals HO() (generated when a reduced redox active metal complex
      interacts with H(2)O(2)) are also probably involved in the oxidative stress that
      creates brain damage during the disease. We report in the present work a method
      to monitor the effect of chelating agents on the production of hydrogen peroxide
      by metallo-amyloid peptides. The addition of H(2)O(2) associated to a pre
      incubation step between ascorbate and AbetaxCu(n) allows to study the formation
      of H(2)O(2) but also, at the same time, its transformation by the copper
      complexes. AbetaxCu(n) peptides produce but do not efficiently degrade H(2)O(2).
      The reported analytic method, associated to precipitation experiments of copper
      containing amyloid peptides, allows to study the inhibition of H(2)O(2)
      production by chelators. The action of a ligand such as EDTA is probably due to
      the removal of the copper ions from AbetaxCu(n), whereas bidentate ligands such
      as 8-hydroxyquinolines probably act via the formation of ternary complexes with
      AbetaxCu(n). The redox activity of these bidentate ligands can be modulated by
      the incorporation or the modification of substituents on the quinoline
      heterocycle.

PMID- 17011627
TI  - Two new scorpionates vanadium haloperoxidases model complexes: synthesis and
      structure of VO(O2)(pzH)(HB(pz)3) and VO(O2)(pzH)(B(pz)4) (pzH =
      pyrazole(C3H4N2)).
AB  - Using vanadate, poly(1H-pyrazol-1-yl)borate and pyrazole as starting materials,
      two new neutral peroxovanadium(V) complexes with poly(1H-pyrazol-1-yl)borate,
      VO(O(2))(pzH)(HB(pz)(3))(1) and VO(O(2))(pzH)(B(pz)(4))(2), were synthesized
      successfully. Both complexes were characterized by elemental analysis, IR, UV-vis
      and NMR spectra. And the structure of complex 1 was determined by X-ray
      diffraction, which is somewhat relevant for haloperoxidase enzymes. Cytotoxic
      effects also are discussed on 3T3 cell proliferation. In the concentration range
      (0.1-100mumol), both complexes have an inhibiting cellular proliferation effect.
      When the cells cultivated with the complexes at high dose, the toxicity effect of
      both complexes is more and more predominant.

PMID- 17011629
TI  - Mechanisms of DNA damage and insight into mutations by chromium(VI) in the
      presence of glutathione.
AB  - The mechanisms of hexavalent chromium(VI) induced DNA damage were unveiled by
      detecting products of single- and double-stranded DNA in the presence of
      glutathione. The absence of a detectable hydroxyl radical in the reactions
      indicates that DNA damage was exclusively by hypervalent chromium species.
      Polyacrylamide gel electrophoresis (PAGE) experiments with 32-mer single-stranded
      oligonucleotide and its complementary duplex revealed cleavages largely at purine
      bases with significant enhancement of such cleavages in the presence of a base.
      Quantitative estimations of bases released by HPLC before and after enzymatic
      digestion with exonucleases unequivocally established the excessive release of
      purine bases. This release was accompanied by the concomitant formation of
      phosphoglycolate as characterized by liquid chromatography-mass spectrometry (LC
      MS). These data connote that the preponderance DNA damage is due to an oxidation
      specifically at H4' of the ribose moiety leading to the formation of apurinic
      sites. In addition to the oxidation at H4', DNA oxidation was also initiated
      through H5' site as evidenced by the identification of furfural. This pathway
      appears to be non-selective and more abundant for ssDNA as cleavages were
      observed at both purine and pyrimidine bases. Finally, the detection of
      guanidinohydantoin as a minor product points the involvement of an oxygen
      activated hypervalent chromium species, perhaps a peroxo-chromium species. Both
      major and minor pathways lead to cleavages at purine sites for ds-DNA and are
      consistent with the observation that DNA cleavage was enhanced in the presence of
      a base. In contrast, when hydrogen peroxide was added to the reactions, random
      DNA cleavages were apparent indicating involvement of multiple species including
      a hydroxyl radical. These data pinpoint mutation mechanisms induced by
      chromium(VI) in the presence of glutathione due to transversion either by
      inserting the wrong bases opposite to the apurinic sites during replication or by
      purine-purine mismatch.

PMID- 17011630
TI  - Reply to: disinfection in diagnostic electron microscopy prior to preparation?

PMID- 17011631
TI  - Tolerance of loop-mediated isothermal amplification to a culture medium and
      biological substances.
AB  - To simplify the molecular detection of micro-organisms, we evaluated the
      tolerance of loop-mediated isothermal amplification (LAMP) to a culture medium
      and some biological substances. The sensitivity of LAMP was less affected by the
      various components of the clinical samples than was polymerase chain reaction
      (PCR); therefore, DNA purification from samples could be omitted.

PMID- 17011633
TI  - Coping patterns as a valid presentation of the diversity of coping responses in
      schizophrenia patients.
AB  - This study aimed to identify coping patterns used by schizophrenia inpatients in
      comparison with those used by healthy individuals, and to explore their
      association with selected clinical and psychosocial variables. The Coping
      Inventory for Stressful Situations (CISS) was used to assess coping strategies
      among 237 inpatients who met DSM-IV criteria for schizophrenia and 175 healthy
      individuals. Severity of psychopathology and distress, insight into illness,
      feelings of self-efficacy and self-esteem (self-construct variables), social
      support, and quality of life were also examined. Factor analysis, analysis of
      covariance and correlations were used to examine the relationships between the
      parameters of interest. Using dimensional measures, we found that emotion
      oriented coping style and emotional distress were significantly higher in the
      schizophrenia group, whereas the task-oriented coping style, self-efficacy,
      perceived social support and satisfaction with quality of life were lower
      compared with controls. When eight CISS coping patterns were defined, the results
      revealed that patients used emotion coping patterns 5.5 times more frequently,
      and task and task-avoidance coping patterns significantly less often than healthy
      subjects. Coping patterns have different associations with current levels of
      dysphoric mood and emotional distress, self-construct variables, and satisfaction
      with quality of life. Thus, the identified coping patterns may be an additional
      useful presentation of the diversity of coping strategies used by schizophrenia
      patients. Coping patterns may be considered an important source of knowledge for
      patients who struggle with the illness and for mental health professionals who
      work with schizophrenia patients.

PMID- 17011632
TI  - Reproductive cycle-associated mood symptoms in women with major depression and
      bipolar disorder.
AB  - BACKGROUND: We sought to determine the prevalence of, and association between,
      reproductive cycle-associated mood symptoms in women with affective disorders. We
      hypothesized that symptoms would correlate with each other across a woman's
      reproductive life span in both major depression (MDD) and bipolar I disorder
      (BP). METHODS: 2412 women with, MDD or BP were asked standardized questions about
      mood symptoms prior to menstruation, within a month of childbirth and during
      perimenopause. Lifetime rates for each of these symptom types were determined and
      an odds ratio was calculated correlating each of the types with the others.
      RESULTS: Of 2524 women with mood disorders, 67.7% reported premenstrual symptoms.
      Of those at risk, 20.9% reported postpartum symptoms and 26.4% reported
      perimenopausal symptoms. The rates did not differ between women with MDD and BP
      but were significantly different from women who were never ill. The symptoms were
      significantly correlated in women with MDD with odds ratios from 1.66 to 1.82,
      but were not in women with BP. LIMITATIONS: This is a secondary analysis of a
      sample that was collected for other purposes and is based upon retrospective
      reporting. CONCLUSIONS: Reproductive cycle-associated mood symptoms were commonly
      reported in women with mood disorders and did not differ based on diagnosis. In
      MDD, but not BP, the occurrence of these symptoms was trait-like as the presence
      of one predicted the occurrence of the others. Further prospective study is
      required to clarify the determinants of this trait.

PMID- 17011634
TI  - Pathological gambling secondary to dopaminergic therapy in Parkinson's disease.
AB  - We describe six patients with Parkinson's disease (PD) and pathological gambling.
      All patients started gambling after the onset of PD and initiation or increase of
      treatment with dopaminergic therapy. The fact that pathological behaviour
      disappeared as medication was ended or decreased suggests that an elaborate
      behavioural manifestation could be related to dopamine tone in patients with
      Parkinson's disease.

PMID- 17011635
TI  - Classifying episodes in schizophrenia and bipolar disorder: criteria for relapse
      and remission applied to recent-onset samples.
AB  - Research on predicting and preventing episodes of schizophrenia and mood disorder
      lacks consistent, specific definitions of episodes. We present an operational
      system for identifying relapse, exacerbation, and remission of schizophrenia and
      bipolar disorder within longitudinal studies that involve repeated symptom
      assessments. Three major classes of episodic outcome are defined: relapse or
      significant exacerbation, nonrelapse, and stable, severe persisting symptoms.
      These major classes are further subdivided to distinguish nine categories of
      episodic outcome. To examine ease of use, interrater reliability, and validity,
      the classification system was applied to recent-onset samples of schizophrenia
      patients (N=77) and bipolar mood disorder patients (N=23) followed on medication
      for 9- to 12-month periods. A range of episodic outcomes were distinguished with
      high interrater reliability. Despite being prescribed continuous medication, 21%
      of the recent-onset schizophrenia patients and 61% of bipolar patients met
      criteria for relapse or significant exacerbation during this follow-up period.
      Predictive relationships support the validity of this system for classifying
      episodes. A computer program is available to facilitate its use. Use of these
      explicit definitions of episodes may help to clarify the relationship between
      episodic outcome and other fundamental domains of illness outcome, particularly
      other symptom dimensions, work functioning, and social functioning.

PMID- 17011636
TI  - Familial resemblance for executive functions in families of schizophrenic and
      bipolar patients.
AB  - Executive dysfunctions are considered to be putative markers of familial/genetic
      vulnerability to both schizophrenia and bipolar disorder. However, familial
      resemblance must be demonstrated before executive functions are used as a
      potential endophenotype. The aim of this study was to investigate familial
      resemblance for executive functions in families of schizophrenic and bipolar
      subjects. We assessed executive functions by means of two tests - the Wisconsin
      Card Sorting Test (WCST) and the Trail Making Test (TMT) - in 351 subjects from
      five populations: schizophrenic patients, bipolar patients, a group of relatives
      for each patient group and controls. For both tests, cognitive assessment results
      were consistent with previous studies: schizophrenic patients showed the greatest
      impairment, followed by bipolar patients and then the two groups of relatives. In
      families of bipolar patients we observed familial resemblance for the WCST and
      part A and part B of the TMT. However, by contrast with the classical point of
      view, considering executive measures to be markers of genetic vulnerability to
      schizophrenia, we did not demonstrate familial resemblance for either of the two
      executive tests in families of schizophrenic patients. Thus, executive measures,
      as assessed by the WCST or the TMT, should not be used as endophenotypes in
      genetic studies of schizophrenia unless confounders are identified and their
      effects eliminated.

PMID- 17011637
TI  - A rodent model for allergic dermatitis induced by flea antigens.
AB  - There have been very few reports of experimentally induced animal models of
      allergic dermatitis, an immunologic disorder. This report describes the induction
      of histopathology confirmed allergic dermatitis in C57BL/6 mice along with the
      consistent clinical sign of alopecia following the administration of flea
      antigens emulsified in complete Freund's adjuvant (CFA). By comparing different
      strains of mice, routes of injection, types of adjuvants and different dosages of
      flea antigens, C57BL/6 mice were found to be most susceptible to flea antigens
      administered intramuscularly (i.m.) and subsequently developed dermatologic
      excoriations and local alopecia. The level of specific IgE reactive to flea
      antigens in C57BL/6 mice after the onset of clinical signs was significantly
      higher than such levels in mice without clinical signs, suggesting that flea
      antigen-specific IgE level can be correlated to the severity of allergic hyper
      reaction. CD4(+) T lymphocytes and IL-4 rather than IL-10, or IFN-gamma were
      found to be the predominant cytokines associated with the clinical onset of
      allergic symptoms in C57BL/6 mice. Further, histopathologic analysis indicated
      that not only mast cells had infiltrated into the area of the skin lesion, but
      the damage was found to be at a stage where mast cells were degranulating causing
      considerable exacerbation of the local injury. In conclusion, this murine
      allergic dermatitis model induced by flea antigens may provide a useful means to
      evaluate vaccines or immunodulatory drugs; thus providing researchers with a tool
      to study allergy-related disorders and other parameters needed in the area of
      allergic investigations.

PMID- 17011638
TI  - Molecular cloning and sequence analysis of interferon-gamma and interleukin-6
      from Tibetan macaque (Macaca thibetana).
AB  - The cloning and sequence analysis of Tibetan macaque IFN-(gamma) and the IL-6
      cDNAs are described. The Tibetan macaque IFN-gamma and IL-6 cDNAs were found to
      be 498 and 639 bp in length, with open reading frames encoding 165 and 212 amino
      acids, respectively. Homology analyses indicated that the identity levels of
      nucleotide and deduced amino acid sequences of IFN-gamma among primates ranged
      from 93.4 to 99.2%, and 87.3 to 99.4%, respectively, and that of IL-6 ranged from
      92.6 to 99.8%, and 85.4 to 99.5%, respectively. Phylogenetic analysis based on
      amino acid sequences showed that the Tibetan macaque is most closely related to
      Old World monkeys, as compared to Hominoidea and New World monkeys. These
      findings provide insights into the evolution of primate IFN-gamma and IL-6 and
      additional valuable information regarding amino acid residues essential for their
      biological activity.

PMID- 17011639
TI  - 5-HT(1B) receptors play a prominent role in the proliferation of T-lymphocytes.
AB  - Serotonin plays a role in T cell activation, but there is no clear consensus of
      which of the 14 serotonergic receptors control this activations pathway. We have
      used a broad range of serotonergic receptor antagonists to define the functional
      involvement of these receptors governing the proliferation of primary T cells as
      well as in T cell lines. Our data shows that antagonism of the 5-HT(1B) receptor
      inhibits the proliferation of both human and murine primary helper T cells and of
      human helper T cell lines. As a whole, our data suggest that other serotonergic
      receptors may contribute to the proliferative signals, but the 5-HT(1B) receptor
      plays the most dominant role.

PMID- 17011640
TI  - Identification of pyruvate kinase as an antigen associated with Tourette
      syndrome.
AB  - Immune responses to beta-hemolytic streptococcal infections are hypothesized to
      trigger tic disorders and early-onset obsessive-compulsive disorder (OCD) in some
      pediatric populations. Here we identify the M1 isoform of the glycolytic enzyme,
      pyruvate kinase (PK) as an autoimmune target in Tourette syndrome and associated
      disorders. Antibodies to PK reacted strongly with surface antigens of infectious
      strains of streptococcus, and antibodies to streptococcal M proteins reacted with
      PK. Moreover, immunoreactivity to PK in patients with exacerbated symptoms who
      had recently acquired a streptococcal infection was 7-fold higher compared to
      patients with exacerbated symptoms and no evidence of a streptococcal infection.
      These data suggest that PK can function as an autoimmune target and that this
      immunoreactivity may be associated with Tourette syndrome, OCD, and associated
      disorders.

PMID- 17011641
TI  - Cardiovascular actions of central neuropeptide W in conscious rats.
AB  - Neuropeptide W (NPW) is a novel hypothalamic peptide that activates the orphan G
      protein-coupled receptors, GPR7 and GPR8. Two endogenous molecular forms of NPW
      that consist of 23- and 30-amino acid residues were identified.
      Intracerebroventricular (i.c.v.) administration of NPW is known to suppress
      spontaneous-feeding at dark-phase and fasting-induced food intake and to decrease
      body weight and plasma growth hormone and to increase prolactin and
      corticosterone; however, little is known about its effect on other physiological
      functions. We examined the effects of i.c.v. administration of NPW30 (0.3 and 3
      nmol) on the mean arterial pressure (MAP), heart rate (HR), and plasma
      norepinephrine and epinephrine in conscious rats. NPW30 (3 nmol) provoked
      increases in MAP (85.12+/-3.16 to 106.26+/-2.66 mm Hg) and HR (305.75+/-13.76 to
      428.45+/-26.82 beats/min) and plasma norepinephrine (138.1+/-18.1 to 297.2+/-25.9
      pg/ml) and epinephrine (194.6+/-21.4 to 274.6+/-22.7 pg/ml). Intravenously
      administered NPW30 (3 nmol) had no significant effects on MAP and HR. These
      results indicate that central NPW30 increases sympathetic nervous outflow and
      affects cardiovascular function.

PMID- 17011642
TI  - The effects of PACAP on neural cell proliferation.
AB  - PACAP and its receptors are expressed in growth zones of the brain. By
      stimulating PAC(1)-receptors PACAP can enhance, as well as reduce, the
      proliferation rate in a cell-type dependent manner. PACAP can enhance the
      proliferation rate by activating phospholipase C and protein kinase C, although
      other signal transduction pathways may also be responsible. PACAP can suppress
      proliferation by inhibiting protein complexes of the cyclins D and E with the
      cyclin-dependent kinases 4/6 and 2, respectively, which are necessary for entry
      into the cell cycle. PACAP seems to exert these inhibitory effects by acting via
      the Sonic hedgehog glycoprotein and the small GTPase RhoA. Also, the activation
      of a cyclin-dependent kinase inhibitor has been suggested. The signal
      transduction pathways mediating the effects of PACAP on proliferation are
      discussed.

PMID- 17011643
TI  - Spermidine/Spermine N1-Acetyltransferase 2 (SSAT2) functions as a coactivator for
      NF-kappaB and cooperates with CBP and P/CAF to enhance NF-kappaB-dependent
      transcription.
AB  - Activation of transcription by NF-kappaB requires association with coactivator
      proteins, including CBP/p300 and P/CAF. To identify new coregulatory proteins, a
      cytoplasmic two-hybrid screen was performed using the C-terminus of the p65
      subunit as bait. Through this screen, the spermidine/spermine N(1)
      acetyltransferase 2 (SSAT2) protein was identified as a potential modulator of NF
      kappaB activity. SSAT2 was originally identified based on homology to SSAT1, a
      protein involved in polyamine catabolism. However both proteins contain an
      acetyltransferase domain that has similarity to the acetyltransferase domains of
      the GNAT superfamily of coactivators. Although SSAT2 is 46% identical to SSAT1,
      based on a recent report, SSAT2 does not appear to function in polyamine
      catabolism. Because of the similarity of SSAT2 to coactivators, we wanted to
      determine if SSAT2 could function as a coactivator for NF-kappaB.
      Coimmunoprecipitations confirmed the interaction between p65 and SSAT2. In
      transient transfection reporter gene assays, SSAT2 functions as a transcriptional
      coactivator for NF-kappaB and cooperates with CBP and P/CAF to enhance TNFalpha
      induced NF-kappaB activity. Moreover, SSAT2 transiently associates with the
      promoters of the NF-kappaB-regulated cIAP2 and IL-8 genes in response to
      TNFalpha. Although the overall function of SSAT2 is not known, it appears that it
      can function as a transcriptional coactivator.

PMID- 17011644
TI  - Uniqueness of the mechanism of protein import into the peroxisome matrix:
      transport of folded, co-factor-bound and oligomeric proteins by shuttling
      receptors.
AB  - Based on earlier suggestions that peroxisomes may have arisen from endosymbionts
      that later lost their DNA, it was expected that protein transport into this
      organelle would have parallels to systems found in other organelles of
      endosymbiont origin, such as mitochondria and chloroplasts. This review
      highlights three features of peroxisomal matrix protein import that make it
      unique in comparison with these other subcellular compartments - the ability of
      this organelle to transport folded, co-factor-bound and oligomeric proteins, the
      dynamics of the import receptors during the matrix protein import cycle and the
      existence of a peroxisomal quality-control pathway, which insures that the
      peroxisome membrane is cleared of cargo-free receptors.

PMID- 17011645
TI  - Isolated pulmonary native valve infectious endocarditis due to Enterococcus
      faecalis.
AB  - We report a case of isolated pulmonary native valve infectious endocarditis due
      to Enterococcus faecalis in a patient without predisposing factors. The early
      diagnostic suspicion plays a pivotal role in this entity. An individual clinical
      and echocardiographic management is mandatory in these patients.

PMID- 17011646
TI  - Prevalence of congenital heart disease in schoolchildren of sub-Saharan Africa,
      Mozambique.
AB  - A survey conducted by cardiologists in Mozambique provided an opportunity for
      assessing the prevalence of congenital heart disease in public school children in
      Maputo. After randomization, a total of 2170 children were examined. Five
      children had clinical and echographic evidence of congenital heart disease,
      corresponding to a prevalence of 2.3 in 1000 (95% confidence interval: 1.0 to
      5.4), 80% newly discovered during the survey. These findings confirm that
      congenital heart disease is at least as common in this South African black
      community as in Caucasians. Early detection of these cardiac diseases in children
      is important in order to prevent serious complications and to institute
      endocarditis prevention.

PMID- 17011647
TI  - Metabolic syndrome and extension of coronary atherosclerosis.

PMID- 17011648
TI  - Advertising and generic market entry.
AB  - The effect of purely persuasive advertising on generic market entry and social
      welfare is analysed. An incumbent has the possibility to invest in advertising
      which affects the prescribing physician's perceived relative qualities of the
      brand-name and the generic version of the drug. Advertising creates product
      differentiation and can induce generic market entry which is deterred without
      differentiation due to strong Bertrand competition. However, over-investment in
      advertising can deter generic market entry under certain conditions and reduces
      welfare as compared to accommodated market entry.

PMID- 17011649
TI  - Magnetic biosensor for the detection of Yersinia pestis.
AB  - A novel type of magnetic-beads based magnetic biosensor is described for the
      detection of Yersinia pestis. Experiments were performed with the antigen
      fraction F1 of these bacteria. The magnetic sensor platform offers easy and
      reliable detection of Y. pestis by the use of magnetic beads for labelling and
      quantification in a single step due to their paramagnetic features. The system
      uses antiYPF1 antibodies as capture element on ABICAP columns as core element of
      the magnetic sensor. Several immobilization methods for antibodies on
      polyethylene were exploited. The established biosensor has a linear detection
      range of 25-300 ng/ml Y. pestis antigen F1 and a detection limit of 2.5 ng/ml in
      buffer and human blood serum. The presented sensor system is small, simple,
      portable and therefore usable as off-lab detection unit for medical and warfare
      analytes.

PMID- 17011650
TI  - Increased frontal phase-locking of event-related theta oscillations in Alzheimer
      patients treated with cholinesterase inhibitors.
AB  - This is a pilot study describing event-related oscillations in patients with
      Alzheimer-type dementia (AD). Theta responses of 22 mild probable AD subjects
      according to NINCDS-ADRDA criteria (11 non-treated, 11 treated by cholinesterase
      inhibitors), and 20 healthy elderly controls were analyzed by using the
      conventional visual oddball paradigm. We aimed to compare theta responses of the
      three groups in a range between 4-7 Hz at the frontal electrodes. At F(3)
      location, theta responses of healthy subjects were phase locked to stimulation
      and theta oscillatory responses of non-treated Alzheimer patients showed weaker
      phase-locking, i.e. average of Z-transformed means of correlation coefficients
      between single trials was closer to zero. In treated AD patients, phase-locking
      following target stimulation was two times higher in comparison to the responses
      of non-treated patients. The results indicate that the phase-locking of theta
      oscillations at F(3) in the treated patients is as strong as the control
      subjects. The F(4) theta responses were not statistically significant between the
      groups. Our findings imply that the theta responses at F(3) location are highly
      unstable in comparison to F(4) in non-treated mild AD patients and cholinergic
      agents may modulate event-related theta oscillatory activities in the frontal
      regions.

PMID- 17011651
TI  - The effects of sleep stages and time of night on NREM sleep ERPs.
AB  - Event-related potential (ERP) is one of the best techniques for studying
      information processing during sleep because it does not require behavioral
      responses or consciousness awareness. Several ERP components have been identified
      during non-rapid eye movement (NREM) sleep, but the associated underlying
      processes of these waveforms remain unclear. The present study examines the
      effect of sleep stage and time of night on the NREM ERPs to further understand
      these processes. An oddball paradigm was conducted in 11 healthy subjects to
      elicit ERPs throughout the night. Polysomnographic recordings were also applied
      to identify sleep stages. The results showed that P220, N350, and P900 decreased
      during the second half of the night, when the NREM sleep drive is partially
      satiated. This finding is consistent with the notion that the NREM ERPs reflect
      an inhibitory process associated with sleep drive. P220 and P900 were also found
      to increase as subjects entering deep sleep. However, the N350 was not affected
      by the deepening of sleep and peaked earlier during stage 1 sleep. Although these
      components are all related to the process for sleep preservation, the N350 may be
      more associated with sleep-wake transition and the P220 and P900 with the process
      of deepening of sleep.

PMID- 17011652
TI  - Prepulse inhibition of the startle blink reflex is modulated during a memory task
      requiring prepulses to be encoded for later report.
AB  - Prepulse inhibition (PPI) of the startle blink reflex in humans can be modulated
      by selective attention to the prepulse. The present experiment used a memory task
      to determine whether the encoding of information for later report can modulate
      PPI. Participants were briefly presented with a display of one or three letters
      followed by a pattern mask and asked to make a delayed report of the letter(s)
      shown. Memory recall was better in the 1-letter condition than in the 3-letter
      condition. Prepulse inhibition was greater in the 3-letter condition than in the
      1-letter condition at lead intervals of 120 and 240 ms following the onset of the
      letter display. Blink modulation did not differ between the letter conditions at
      lead intervals of 120, 240, 360, or 2600 ms following the mask, ruling out other
      explanations (e.g., rehearsal) for the earlier difference in PPI. The results
      suggest that the short-term consolidation of memory, and possibly any cognitive
      process that requires access to a theoretical limited capacity central processing
      mechanism modulates PPI.

PMID- 17011653
TI  - Attention and movement execution during handwriting.
AB  - Two studies were performed in order to test the hypothesis that movement
      execution during handwriting in skilled writers is independent of attention.
      Study I examined the relationship between attentional functioning and kinematic
      aspects of handwriting movements in 24 adult participants. A digitizing tablet
      was used for the assessment of handwriting movements. Participants were asked to
      perform a simple writing task and various components of their attention were
      assessed. Correlation analysis indicated no significant relationship between
      attention functions and both kinematic aspects of handwriting movements and
      quality of handwriting. In Study II, 20 participants underwent total sleep
      deprivation (TSD) for 24h. While attention, as assessed with alertness and
      vigilance tasks, deteriorated during TSD, the execution of handwriting movements,
      as assessed with a digitizing tablet, improved markedly. The quality of
      handwriting was not affected by TSD. These findings may suggest an independence
      between attention and movement generation during handwriting.

PMID- 17011654
TI  - Bimanual interference in children performing a dual motor task.
AB  - The present study addressed the development of bimanual interference in children
      performing a dual motor task, in which each hand executes a different task
      simultaneously. Forty right-handed children (aged 4, 5-6, 7-8 and 9-11years, ten
      in each age group) were asked to perform a bimanual task in which they had to tap
      with a pen using the non-preferred hand and simultaneously trace a circle or a
      square with a pen using the preferred hand as quickly as possible. Tapping and
      tracing were also performed unimanually. Differences between unimanual and
      bimanual performance were assessed for number of taps, length of tap trace and
      mean tracing velocity. It was assumed that with increasing age, better bimanual
      coordination would result in better performance on the dual task showing less
      intermanual interference. The results showed that tapping and tracing performance
      increased with age, unimanually as well as bimanually, consistent with
      developmental advancement. However, the percentage of intermanual interference
      due to bimanual performance was not significantly different in the four age
      groups. Although performing the dual task resulted in mutual intermanual
      interference, all groups showed a significant effect of tracing shape. More
      specifically, all age groups showed a larger percentage decrease in tracing
      velocity when performing the circle compared to the square in the dual task. The
      present study reveals that children as young as four years are able to coordinate
      both hands when tapping and tracing bimanually.

PMID- 17011655
TI  - Abrupt, but not gradual visuomotor distortion facilitates adaptation in children
      with developmental coordination disorder.
AB  - A previous experiment investigating visuomotor adaptation in typically developing
      children and children with Developmental Coordination Disorder (DCD) suggested
      poor adaptation to an abruptly induced visuomotor perturbation. In the current
      study, using a similar center-out drawing task, but administering either an
      abrupt or a gradual perturbation, and twice as many adaptation trials, we show
      that typically developing children are well able to successfully update an
      existing internal model in response to a 60 degrees rotation of the visual
      feedback, independent of the perturbation condition. Children with DCD, however,
      updated their internal map more effectively during exposure to an abrupt
      visuomotor perturbation than to a gradual one. This may suggest that the
      adaptation process in children with DCD responds differently to small vs. large
      steps of visuomotor discrepancies. Given the known role of the cerebellum in
      providing an error signal necessary for updating the internal model in response
      to a gradual visuomotor distortion, the results of our study add to the growing
      body of evidence implicating compromised cerebellar function in DCD.

PMID- 17011656
TI  - Automatic segmentation as a tool for examining the handwriting process of
      children with dysgraphic and proficient handwriting.
AB  - The purpose of this study was to use an x-y digitizer to collect handwriting
      samples typical of those written by the child in his or her natural environment,
      to analyze these samples with novel segmentation algorithms, and to present them
      visually in ways that illuminate spatial and temporal dynamic features amongst
      children with dysgraphic and proficient handwriting. While using the POET
      software (Penmanship Objective Evaluation Tool), a paragraph was copied onto
      paper affixed to an x-y digitizer by third-grade students, 14 with proficient and
      14 with poor handwriting. A segmentation algorithm was developed to automatically
      isolate writing segments. Results yielded significant differences between the
      groups in various measures, including the number of the raw segments (i.e., the
      number of segments before combined with letters), the number of reverse segments
      (i.e., when the participant returned to correct or complete a previously written
      segment), the number of letters per minute, and the mean "In-Air" time between
      letters. Variability in both the spatial and temporal domains of instances of the
      same letter throughout the text was greater among the dysgraphic handwriters in
      comparison to the variability among the proficient. These results demonstrated
      the potential of using automated analytic techniques and visual display to
      achieve a more comprehensive understanding of handwriting difficulties.

PMID- 17011657
TI  - Effects of increased complexity of visuo-motor transformations on children's arm
      movements.
AB  - The effects of increasing complexity of visuo-motor transformations on movement
      were examined in 4-, 6-, and 8-year-old children and adults. Participants
      performed a 'center-out' drawing task under three increasingly complex
      conditions: (1) Normal transformation: The target, line path and hand position
      were fully visible, in the horizontal plane, throughout the movement. (2) Aligned
      transformation: The target and line path were displayed horizontally above the
      workspace, with vision of the arm/hand occluded. (3) Vertical transformation: The
      target and line paths were presented on a vertical computer monitor with vision
      of the arm/hand occluded. Results showed that with increasing age, movements
      became faster, straighter, and smoother. The 4- and 6-year-old children were more
      variable in their specification of movement direction than the 8-year-old
      children and the adults, and were also more affected by the complexity of the
      transformation. This suggested that besides the complexity of the visual
      transformation, the familiarity/experienced environment might also play a role in
      'sharpening' the transformation maps represented in movement planning.

PMID- 17011658
TI  - Developmental differences in drawing performance of the dominant and non-dominant
      hand in right-handed boys and girls.
AB  - This paper addresses the development of fine motor skills in the dominant and non
      dominant hand. A total of 60 right-handed children, aged 4-12 years old, were
      divided in five groups of 12 children, with six girls and six boys in each group.
      The children were presented with drawing tasks that had to be performed with the
      dominant and non-dominant hand. Small or large targets had to be connected by
      lines making either a zigzag (discrete) or slalom (continuous) movement. For each
      task, effects of age group, gender, hand, and target size were examined for
      drawing time, percentage of stop time, drawing distance, velocity, and errors.
      Comparison of stop times in both tasks showed that the zigzag task was performed
      in a discrete way while the slalom task was performed more continuously, except
      in the youngest children, who performed both tasks in a discrete manner. With
      increasing age the children performed the tasks faster, more accurate and with
      shorter stops. No significant differences were found between boys and girls.
      While a shorter drawing distance and less errors were observed for the dominant
      hand in both tasks, drawing time and velocity were not significantly different
      between both hands. However, the percentage of stop time was higher for the
      dominant hand. Moving to smaller targets resulted in slower and less accurate
      performance. A significant interaction of age group and hand was found for errors
      in both tasks, and for stop time and velocity in the slalom task, suggesting
      differential maturational changes for both hands in discrete and continuous
      drawing tasks.

PMID- 17011659
TI  - Development of forward models for hand localization and movement control in 6- to
      10-year-old children.
AB  - An active kinesthetic-to-visual matching task was performed by 15 children aged 5
      10 years and five young adults. The task required the participants to locate the
      target visually while performing center-out drawing movements to the located
      visual targets in the absence of visual feedback of hand/pen motion. Movement
      time (MT), terminal end-point position error (EPE), and initial directional error
      (IDE) were measured. The general finding is that the end-point error variability,
      representing the joint localization probability distributions for proprioceptive
      localization of the hand and visual localization of the target, was largest for
      the youngest children, but did not differ from one another for the older age
      groups. The localization distributions, as characterized by principal component
      analysis, showed that both errors in extent and direction were significantly
      larger in the youngest children. These error distributions could not be accounted
      for by initial localization errors prior to movement onset in the children. It is
      likely that at least some portion of the increased movement variability seen
      during sensorimotor development in young children can be attributed not only to
      immature control mechanisms per se, but also to partial, not yet stable, forward
      representations for hand localization which are used for movement perception,
      planning, and control.

PMID- 17011660
TI  - Remembering the orientation of newly learned characters depends on the associated
      writing knowledge: a comparison between handwriting and typing.
AB  - Recent data support the idea that movements play a crucial role in letter
      representation and suggest that handwriting knowledge contributes to visual
      recognition of letters. If so, using different motor activities while subjects
      are learning to write should affect their subsequent recognition performances. In
      order to test this hypothesis, we trained adult participants to write new
      characters either by copying them or by typing them on a keyboard. After three
      weeks of training we ran a series of tests requiring visual processing of the
      characters' orientation. Tests were ran immediately, one week after, and three
      weeks after the end of the training period. Results showed that when the
      characters had been learned by typing, they were more frequently confused with
      their mirror images than when they had been written by hand. This handwriting
      advantage did not appear immediately, but mostly three weeks after the end of the
      training. Our results therefore suggest that the stability of the characters'
      representation in memory depends on the nature of the motor activity produced
      during learning.

PMID- 17011661
TI  - Combined effect of volatile antimicrobial agents on the growth of Penicillium
      notatum.
AB  - Widely used antimicrobial volatile organic compounds, such as sulphur dioxide and
      ethanol but also selected aroma compounds such as carvacrol, allyl isothiocyanate
      (AITC) and cinnamaldehyde, were tested single and in binary combination for their
      effect on Penicillium notatum growth in vapour phase at 30 degrees C. Aroma
      compounds were more efficient compared to sulphur dioxide and ethanol. AITC and
      cinnamaldehyde had the highest inhibition activity on the growth of P. notatum
      with minimum inhibitory concentration (MIC) of 3.8 and 3.9 micromol/L of air,
      respectively. The impact of agents combined two by two was assessed using two
      criteria, the increase of growth delay and the reduction of growth rate. A
      synergistic activity was identified for six combinations; ethanol/carvacrol,
      sulphur dioxide/carvacrol, sulphur dioxide/AITC, sulphur dioxide/cinnamaldehyde,
      AITC/cinnamaldehyde and cinnamaldehyde/carvacrol. The advantage of these
      combinations is to reduce the concentration of each agent and their relative
      impact in organoleptic properties.

PMID- 17011662
TI  - Insulin glargine versus NPH insulin therapy in Asian Type 2 diabetes patients.
AB  - OBJECTIVE: This study investigated the effect of insulin glargine (LANTUS) versus
      NPH insulin on metabolic control and safety in Asian patients with Type 2
      diabetes, inadequately controlled on oral hypoglycemic agents (OHAs). STUDY
      DESIGN AND METHODS: In this open-label, randomized, parallel, multinational, 24
      week, non-inferiority study, 443 patients received either once-daily insulin
      glargine (n=220) or NPH insulin (n=223) at bedtime, plus glimepiride (Amaryl).
      RESULTS: Baseline characteristics were similar between the two groups. HbA(1c)
      levels decreased in the insulin glargine and NPH groups over the study period in
      the per-protocol (PP; -1.10% versus 0.92%) and full-analysis (FA; -0.99% versus 
      0.77%) populations. In the PP population, the difference between adjusted means
      (predefined equivalence region >-0.4%) was 0.19% (90% confidence interval [CI]:
      0.02, 0.36), demonstrating non-inferiority between the two treatments. In a
      superiority analysis (FA population), the difference between adjusted mean
      changes in the two groups was 0.22% (95% CI: 0.02, 0.42), demonstrating the
      superiority of insulin glargine (p=0.0319). Moreover, the number of hypoglycemic
      episodes was significantly lower with insulin glargine versus NPH insulin
      (p<0.004), particularly severe (p<0.03) and nocturnal (p<0.001). Daily insulin
      dose increased from 9.6+/-1.5 to 32.1+/-17.6 U in the insulin glargine group and
      from 9.8+/-1.9 to 32.8+/-18.9 U in the NPH insulin group. CONCLUSION: These
      results confirm earlier reports that insulin glargine provides superior glycemic
      control with less hypoglycemia and demonstrates that these benefits are
      consistent between different ethnicities.

PMID- 17011664
TI  - Molecular evolution of plant immune system genes.
AB  - Molecular population genetic studies are providing new perspectives on the
      evolution of genes that confer resistance to pathogens and herbivores. Here, we
      compare the evolutionary history of different components of the defense response
      (detection, signaling and response) and of genes with parallel function in plants
      and Drosophila. A review of the literature indicates that the dominant form of
      selection acting on defense genes (balancing, positive and purifying) differs
      among components of defense. Sampling of particular classes of genes and genes
      from non-model organisms, however, remains limited. Future studies combining
      molecular evolutionary analyses with ecological genetic and functional analyses
      should better reveal how natural selection has shaped defense gene evolution.

PMID- 17011663
TI  - Novel roles of the IGF-IGFBP axis in etiopathophysiology of diabetic nephropathy.
AB  - Mechanisms contributing to development of diabetic nephropathy (DN) remain
      unclear. High ambient glucose level transforms intracellular pathways, promoting
      stable phenotypic changes in the glomerulus such as mesangial cell hypertrophy,
      podocyte apoptosis, and matrix expansion. Insulin-like growth factors (IGFs) and
      the high affinity IGF binding proteins (IGFBPs) exert major effects on cell
      growth and metabolism. Compared with diabetic patients without microalbuminuria
      (MA), MA diabetic patients display perturbed GH-IGF-IGFBP homeostasis, including
      increased circulating IGF-I and IGFBP-3 protease activity, increased excretion of
      bioactive GH, IGF-I, and IGFBP-3, but decreased circulating IGFBP-3 levels. In
      diabetic animal models, expression of IGF-I and IGFBP-1 to -4 increases in key
      renal tissues and glomerular ulrafiltrate. Epithelial, mesangial, and endothelial
      cells derived from the kidney respond to IGF-I binding with increased protein
      synthesis, migration, and proliferation. This article reviews classic and
      emerging concepts for the roles of the GH-IGF-IGFBP axis in the
      etiopathophysiology, treatment, and prevention of diabetic renal disease. We
      report IGF-independent actions of IGFBP-3 in the podocyte for the first time.

PMID- 17011665
TI  - Validation of biocides against duck hepatitis B virus as a surrogate virus for
      human hepatitis B virus.
AB  - The use of a surrogate virus, namely duck hepatitis B virus (DHBV), has been
      recommended for testing the virucidal activity of chemical biocides against
      hepatitis B virus. To date, however, this model has not been recognized as a
      standard test in European countries, as its laboratory use is associated with
      considerable difficulties. As previous studies have demonstrated, several
      alternative procedures may improve the validation of DHBV infection in a cell
      culture system. Using indirect immunofluorescent antigen staining and the light
      cycler real-time polymerase chain reaction (PCR) technique, the virucidal
      activity of peracetic acid (PAA), povidone-iodine (PVP-I) and formaldehyde was
      tested against DHBV obtained from congenitally infected ducks or prepared from
      the transfected hepatoma D2 cell line. The results demonstrated that inactivation
      of DHBV from the D2 cell line was achieved with lower concentrations of the
      biocides and within shorter exposure time intervals. These lower concentration
      exposure time values for DHBV from D2 cells in comparison with DHBV from infected
      ducks indicated a higher sensitivity of the virus derived from D2 cells. In
      addition, concentrations of PAA and PVP-I that significantly inactivated DHBV in
      suspension tests were not able to destroy the viral genome. In conclusion, DHBV
      from congenitally infected ducks should be used for virucidal testing of chemical
      biocides against DHBV; DHBV prepared from D2 cells is unsuitable due to its
      higher sensitivity to biocides. Indirect immunofluorescent staining allows
      reliable detection of DHBV infectivity, whereas the hepadnavirucidal effect can
      be evaluated by quantitative PCR.

PMID- 17011666
TI  - ProTECT: a randomized clinical trial of progesterone for acute traumatic brain
      injury.
AB  - STUDY OBJECTIVE: Laboratory evidence indicates that progesterone has potent
      neuroprotective effects. We conducted a pilot clinical trial to assess the safety
      and potential benefit of administering progesterone to patients with acute
      traumatic brain injury. METHODS: This phase II, randomized, double-blind, placebo
      controlled trial was conducted at an urban Level I trauma center. One hundred
      adult trauma patients who arrived within 11 hours of injury with a
      postresuscitation Glasgow Coma Scale score of 4 to 12 were enrolled with proxy
      consent. Subjects were randomized on a 4:1 basis to receive either intravenous
      progesterone or placebo. Blinded observers assessed patients daily for the
      occurrence of adverse events and signs of recovery. Neurologic outcome was
      assessed 30 days postinjury. The primary safety measures were differences in
      adverse event rates and 30-day mortality. The primary measure of benefit was the
      dichotomized Glasgow Outcome Scale-Extended 30 days postinjury. RESULTS: Seventy
      seven patients received progesterone; 23 received placebo. The groups had similar
      demographic and clinical characteristics. Laboratory and physiologic
      characteristics were similar at enrollment and throughout treatment. No serious
      adverse events were attributed to progesterone. Adverse and serious adverse event
      rates were similar in both groups, except that patients randomized to
      progesterone had a lower 30-day mortality rate than controls (rate ratio 0.43;
      95% confidence interval 0.18 to 0.99). Thirty days postinjury, the majority of
      severe traumatic brain injury survivors in both groups had relatively poor
      Glasgow Outcome Scale-Extended and Disability Rating Scale scores. However,
      moderate traumatic brain injury survivors who received progesterone were more
      likely to have a moderate to good outcome than those randomized to placebo.
      CONCLUSION: In this small study, progesterone caused no discernible harm and
      showed possible signs of benefit.

PMID- 17011667
TI  - Sequence diversity of O-superfamily conopetides from Conus marmoreus native to
      Hainan.
AB  - The full-length cDNAs of six new O-superfamily conotoxins (CTX) were cloned and
      sequenced from Conus marmoreus native to Hainan in China South Sea using RT-PCR
      and 3'-RACE. Six novel conotoxin precursors encoded by these cDNAs consist of
      three typical regions of signal, pro-peptide and mature peptide. All the six
      toxin regions share a common O-superfamily cysteine pattern (C-C-CC-C-C, with
      three disulfide bridges). The predicted precursors are composed of 73-88 amino
      acids, and the predicted mature peptides consist of 26-34 amino acids.
      Phylogenetic analysis of new conotoxins from C. marmoreus from the present study
      and published homologue T-superfamily sequences from other Conus species was
      performed systematically. Patterns of sequence divergence for three regions of
      signal, pro-region and mature peptides, as well as Cys codon usage define the
      major O-superfamily branches and suggest how these separate branches arose.
      Percent identities of the amino acid sequences of the signal region exhibited
      high conservation, whereas the sequences of the mature peptides ranged from
      almost identical to highly divergent between inter- and intra-species. Notably,
      the diversity of the pro-region was also high with intermediate divergence
      between that observed in signal and toxin regions. Amino acid sequences and their
      mode of action (target) of previously identified conotoxins from molluscivorous
      C. marmoreus for the known conotoxins classes are discussed in detail. The data
      presented are new and should pave the way for chemical synthesis of these unique
      conotoxins for to allow determination of the molecular targets of these peptides,
      and also to provide clues for a better understanding of the phylogeny of these
      peptides.

PMID- 17011668
TI  - GRK5 deficiency leads to early Alzheimer-like pathology and working memory
      impairment.
AB  - G-protein coupled receptor kinase-5 (GRK5) deficiency has been linked to early
      Alzheimer's disease in humans and mouse models of the disease. To determine
      potential roles of GRK5 in the disease pathogenesis, the GRK5 knockout mouse was
      evaluated at pathological and behavioral levels. We found that these mice
      displayed an age-dependent increase in hippocampal axonal defects characterized
      by clusters of axonal swellings that accumulated abnormal amounts of molecular
      motor proteins, microtubule-associated proteins, intracellular beta-amyloid, and
      subcellular organelles. In severe cases, extracellular beta-amyloid fibrillar
      deposits were occasionally observed, along with degenerating axonal components,
      and were tightly surrounded by reactive astrocytes. Moreover, significant loss of
      synaptic proteins and early signs of cholinoceptive neurodegeneration were
      evident in the hippocampus as well. Consistent with the moderate level of
      pathologic change, aged GRK5 knockout mice displayed selective working memory
      impairment, with other cognitive domains unaffected. Taken together, these
      findings not only strongly support an important role of GRK5 deficiency in early
      Alzheimer's pathogenesis, but also promote the GRK5 knockout mouse as an
      additional model for early Alzheimer-related studies.

PMID- 17011669
TI  - Genes related to iron metabolism and susceptibility to Alzheimer's disease in
      Basque population.
AB  - Alzheimer's disease (AD) is the most common dementing disorder and presents with
      a progressive and irreversible cognitive decline of gradual onset. To date,
      several reports have involved iron in AD physiopathology. In this study, we have
      analysed TFC2 variant and HFE mutations (H63D and C282Y) in 211 AD patients and
      167 controls recruited from an area of the Basque Country. Furthermore, we have
      studied APOE genotype as it is a well-known risk factor for AD. APOE epsilon 4
      allele was associated with an increased risk of AD and an earlier age at onset,
      whereas no association was found between TFC2 or HFE C282Y mutation and disease
      susceptibility. The frequency of H63D mutation was higher in control population
      (29.9%) than in AD patients (18%), suggesting a protective role of this allele on
      AD either due to the presence of the mutation itself or through the effect of
      other related genes in the ancestral haplotype in which it is included.

PMID- 17011670
TI  - Synthesis, characterization and in vitro biological activity studies of Cu-M (M =
      Cu2+, Co2+, Ni2+, Mn2+, Zn2+) bimetallic complexes.
AB  - Six new bimetallic complexes of the type CuCu, CuCo, CuNi, CuZn and CuMn were
      prepared. The structures of these complexes and the ligand have been proposed on
      the basis of FAB mass, elemental analysis, UV-vis, IR, EPR and CV studies. All
      the complexes completely cleave pBS (SK-) DNA at a concentration of 10 microM;
      however, even at lower concentrations of 2 microM and 0.1 microM, the complexes
      (I and Ia) showed partial cleavage. The results of the fluorescence binding
      studies of the metal complexes with CT-DNA showed that the presence of aliphatic
      ligands added additional binding effects including electrostatic, hydrogen
      binding and vander Waals interactions. Complexes (I, Ia) showed 50% inhibition of
      COX-1 and COX-2 activities at as low a concentration as 12.5 microM, 13.5 microM,
      14 microM and 14.5 microM. Inhibition assay of top I and top II by different
      complexes in mutant yeast strains (JN394, JN394 t(-1) and JN394 t(2-5)) with all
      the complexes showed significant inhibition of topoisomerase at 5 microM
      concentration. Complexes I and Ia exhibited good anti-microbial activities
      against all human pathogens tested except Klebsiella pneumoniae. The following
      studies showed that among the synthesized bimetallic complexes, complexes I and
      Ia seem to be promising candidates possessing DNA cleavage activities besides
      anti-microbial and anti-inflammatory properties to serve as chemical nucleases
      and chemotherapeutic agents.

PMID- 17011671
TI  - Synthesis of versatile chemical tools toward a structure/properties relationships
      study onto targeting colloids.
AB  - As part of a drug delivery project, four aldehydes of the type Pam-Lys(Pam)
      spacer-CO-CHO were synthesized to be included in targeting colloids. Though
      amphiphilic, they were obtained within reasonable yields (18-55%) and with high
      RP-HPLC purity ( approximately 90%). Parallely, six complementary targeting
      peptides of the type H(2)N-NH-CH(2)-CO-spacer-YGRGDSP-NH(2) were prepared to be
      anchored onto colloids. Isolated yields are related to the spacer length and
      nature. To easily and rapidly modulate the distance between the peptide and the
      vesicle, every partners were elaborated on solid phase and the expected
      constructions were obtained by hydrazone ligation. One possible application is
      presented here with multilamellar vesicles targeting HUVEC cells. Preliminary
      results prove that the fine-tuning of the spacer length permits to optimize the
      recognition toward the target cells.

PMID- 17011673
TI  - Developing clinical placements in times of scarcity.
AB  - This article takes the position that the current shortage of clinical placements
      may be creating problems, but it can also be seen as an opportunity to reconsider
      the design of students' clinical experiences and the goals to be attained. It
      begins with a description of paradoxes in professional education. The following
      sections examine some of the considerations which need to be incorporated in the
      development of clinical placements and the way they are incorporated into health
      care courses. The considerations germane to clinical placement development
      include social participation in clinical settings, communities of learning, and
      consumer-centred inter-professional collaboration.

PMID- 17011674
TI  - A mobile clinical e-portfolio for nursing and medical students, using wireless
      personal digital assistants (PDAs).
AB  - This paper outlines the development and evaluation of a wireless personal digital
      assistant (PDA) based clinical learning tool designed to promote professional
      reflection for health professionals. The "Clinical e-portfolio" was developed at
      the University of British Columbia School of Nursing to enable students
      immediately to access clinical expertise and resources remotely, and record their
      clinical experiences in a variety of media (text, audio and images). The PDA e
      portfolio tool was developed to demonstrate the potential use of mobile networked
      technologies to support and improve clinical learning; promote reflective
      learning in practice; engage students in the process of knowledge translation;
      help contextualize and embed clinical knowledge whilst in the workplace; and to
      help prevent the isolation of students whilst engaged in supervised clinical
      practice. The mobile e-portfolio was developed to synchronise wirelessly with a
      user's personal Web based portfolio from any remote location where a cellular
      telephone signal or wireless (Wi-Fi) connection could be obtained. An evaluation
      of the tool was undertaken with nurse practitioner and medical students,
      revealing positive attitudes to the use of PDA based tools and portfolios, but
      limits to the use of the PDA portfolio due to the inherent interface restrictions
      of the PDA.

PMID- 17011675
TI  - Factors shaping Aboriginal nursing students' experiences.
AB  - Motivated by a shortage of Aboriginal nurses and recurring difficulties in
      recruitment and retention of Aboriginal peoples in nursing education, a critical
      ethnography was conducted to examine the experiences of undergraduate Aboriginal
      nursing students in two Canadian schools of nursing. We conducted audiotaped
      interviews with Aboriginal nursing students (n=31), Aboriginal nurses (n=5),
      nursing faculty members (n=24), and individuals who were identified as
      knowledgeable about the context that might shape the experiences (n=16). Other
      data sources included reflexive and descriptive fieldnotes from 200 h of
      fieldwork in classroom and laboratory practice sessions and 135 texts from the
      participating schools. Nursing textbooks, course syllabi, policies, procedures,
      clinical evaluation forms and websites were randomly selected and analyzed to
      explicate how texts shaped the students' experiences. In this paper, we discuss
      the findings of the study and briefly share our recommendations.

PMID- 17011676
TI  - Beta-hydoxy-beta-methylbutyrate supplementation affects Walker 256 tumor-bearing
      rats in a time-dependent manner.
AB  - BACKGROUND & AIMS: Cancer cachexia affects intermediary metabolism with intense
      and general catabolism. Walker 256 tumor is a model injected either
      subcutaneously (Sc) or intraperitoneally (Ip), with different metabolic features.
      Beta-hydroxy beta-methylbutyrate (HMbeta) is a leucine metabolite with anti
      catabolic properties, the aim of this study being to investigate its effects on
      metabolic parameters in both tumor models. METHODS: Controls (subcutaneous
      control group (ScC) and intraperitoneal control group (IpC)) and supplemented
      animals (subcutaneous supplemented group (ScS) and intraperitoneal supplemented
      group (IpS)) showed these results. RESULTS: Protein Sc values were (47.8%) lower
      than Ip groups. Sc group fat content was (65.16%) higher than Ip groups. Liver
      glycogen value for Sc groups was (38.4%) higher than Ip groups. Muscle glycogen
      value for Sc groups were (2.75 times) higher than Ip groups. Corticosterone and
      insulin values were lower (44.53%) and higher (45.94%), respectively, in Sc when
      compared with Ip groups. Glucose and lactate values for ScS were the lowest
      (61.7% and 41.53%) compared to other groups. ScC glutamine value was the highest
      (40.8%) of all groups. Glutamate Sc values were (42.65%) lower than Ip groups. Sc
      groups showed greater survival time compared with Ip groups. ScS group showed
      100% increase in survival time when compared with ScC. CONCLUSIONS: HMbeta
      supplementation can increase survival time and promotes metabolic changes in
      cancer-bearing animals, but it seems to work in a time-dependent manner.

PMID- 17011677
TI  - Evaluation of vaccine Encepur Adult for induction of human neutralizing
      antibodies against recent Far Eastern subtype strains of tick-borne encephalitis
      virus.
AB  - We studied humoral immune response of 44 volunteers from Primorsky krai (Russia)
      immunized with the vaccine Encepur Adult. Induction of the humoral response
      towards the recently isolated tick-borne encephalitis virus (TBEV) strains P-69,
      P-202, and P-73 was evaluated by neutralization test and enzyme immunoassay.
      These strains belong to Far Eastern TBEV subtype based on their genotype and
      antigenic structure but maintain significant genetic and antigenic variability.
      The average geometric titers of neutralizing antibodies to P-69, P-202, and P-73
      strains were 1:28, 1:34, and 1:128, respectively. The percentage of volunteers
      with neutralizing antibodies to these strains after complete course immunization
      was 63.9, 97.6, and 95.5%, respectively. We concluded that Encepur Adult vaccine
      induced pronounced humoral immune response towards genetically and antigenically
      heterogeneous strains of the Far Eastern TBEV subtype.

PMID- 17011678
TI  - Antibody responses after dose-sparing intradermal influenza vaccination.
AB  - Reduced-dose intradermal (ID) influenza vaccination is an attractive approach to
      increase availability of vaccine supply in an event of vaccine shortage. We
      conducted a randomized open-label study, in which 500 subjects were randomly
      assigned to receive an ID injection of 0.1 ml dose of inactivated split-virion
      influenza vaccine or an IM injection of 0.5 ml dose. The subjects who had
      hemagglutination inhibition (HI) antibody titer of at least 1:40 at day 28 post
      vaccination in ID and IM groups were 93.3% versus 98.0% for influenza A(H1N1)
      virus, 86.3% versus 95.0% for A(H3N2) virus, and 43.5% versus 57.0% for influenza
      B virus. Subjects in the ID group had an increase in geometric mean titer by a
      factor of 16 for the H1N1 strain, 8 for the H3N2 strain, and 2 for the B strain
      on day 28, as compared with respective increase in the IM group of 31, 20, and 3.
      Local reactions were significantly more frequent among subjects in the ID group
      than those in the IM group, but the reactions were mild and transient. In this
      study, ID administration of one-fifth dose of influenza vaccine elicited
      significantly lower levels of antibody response as compared to full-dose IM
      injection. However, the antibody responses elicited by the ID vaccination were
      still sufficiently high to meet the requirement guidelines of the European
      Committee for Proprietary Medicinal Products (CPMP) for the annual relicensure of
      influenza vaccines.

PMID- 17011679
TI  - SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces
      neutralizing antibodies in rabbits pre-immunized with vaccinia virus.
AB  - A vaccine for severe acute respiratory syndrome (SARS) is being intensively
      pursued against its re-emergence. We generated a SARS coronavirus (SARS-CoV)
      spike protein-expressing recombinant vaccinia virus (RVV-S) using highly
      attenuated strain LC16m8. Intradermal administration of RVV-S into rabbits
      induced neutralizing (NT) antibodies against SARS-CoV 1 week after administration
      and the NT titer reached 1:1000 after boost immunization with RVV-S.
      Significantly, NT antibodies against SARS-CoV were induced by administration of
      RVV-S to rabbits that had been pre-immunized with LC16m8. RVV-S can induce NT
      antibodies against SARS-CoV despite the presence of NT antibodies against VV.
      These results suggest that RVV-S may be a powerful SARS vaccine, including in
      patients previously immunized with the smallpox vaccine.

PMID- 17011680
TI  - Adjuvant and immunogenic activities of the 73kDa N-terminal alpha-domain of BrkA
      autotransporter and Cpn60/60kDa chaperonin of Bordetella pertussis.
AB  - A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant
      for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine.
      High levels of antibodies were induced, and a 78% protection rate of mice
      challenged with live B. pertussis was observed. Two proteins were identified as
      the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the
      Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced
      a 42% protection rate against the challenge. IgG1 and IgG2a were stimulated
      suggesting that the immune response could be modulated to produce Th1 or Th2.

PMID- 17011681
TI  - A comparative study of the effect of food consumption on labour and birth
      outcomes in Australia.
AB  - OBJECTIVE: to explore the effect of volitional food consumption by women during
      labour on labour and birth outcomes. DESIGN: a comparative design using
      concurrent controls. SETTING: four public hospitals in Sydney, Australia.
      PARTICIPANTS: 217 English-speaking, nulliparous women with low-risk pregnancies.
      The sample was divided into four sub-groups identified post hoc from reported
      behaviour: (1) 82 women who chose to eat food during early labour only; (2) 10
      who ate during established labour only; (3) 31 who ate during early and
      established labour and (4) 94 who chose to consume clear fluids only during early
      and established labour. INTERVENTIONS: voluntarily eating food during labour
      compared with voluntarily consuming clear fluids only. MEASUREMENTS: differences
      between the four eating groups were examined for labour progress using one-way
      analysis of variance (ANOVA). A hierarchical multiple regression tested the
      association between eating during labour and labour duration. The relationship
      between food intake and the incidence of medical interventions was tested using
      chi(2) tests. FINDINGS: eating during the early phase of the first stage of
      labour was associated with M=2.16 hrs longer labour (p<0.01). When women ate food
      during both their early and established phases of labour, M=3.5 hrs was added to
      their labour (p<0.01). The incidence of vomiting, medical interventions during
      labour or adverse birth outcomes were unaffected by food intake. CONCLUSION: the
      findings suggest that women should be informed that labour may take longer when
      they eat food. However, eating does not seem to affect other labour or birth
      outcomes. IMPLICATION FOR PRACTICE: the findings challenge the belief among many
      midwives that food intake is beneficial to labour progress. However, women should
      not be denied food for fear of vomiting or because it may make labour longer.
      Women with low-risk labours should be informed of the risk, although rare, of
      aspiration if general anaesthesia is required, and be allowed to respond to their
      natural desires for oral intake during labour.

PMID- 17011682
TI  - An exploration of the relationship between postnatal distress and maternal role
      attainment, breast feeding problems and breast feeding cessation in Australia.
AB  - OBJECTIVES: To explore the relationships between maternal distress, breast
      feeding cessation, breast feeding problems and breast feeding maternal role
      attainment. DESIGN: Longitudinal cohort study. SETTING: Three urban hospitals
      within Sydney, Australia. PARTICIPANTS: 449 women were invited to participate in
      the study, with an 81% response rate. MEASUREMENT: Self-report questionnaires
      were used to collect the data in pregnancy (28-36 weeks) and 2 weeks and 3 months
      after birth. The Edinburgh Postnatal Depression Scale (EPDS) was used to measure
      postnatal distress, and the Maternal Role Attainment subscale (MRA) of the
      Maternal Breast Feeding Evaluation Scale (MBFES) was used to measure breast
      feeding maternal role attainment. FINDINGS: Women with high MRA were less likely
      to stop breast feeding (even when they had breast feeding problems) than women
      with low MRA. Antenatal EPDS and anxiety scores were not related to breast
      feeding cessation or breast feeding problems when analysed alone. As
      hypothesised, the relationship between breast feeding cessation and postnatal
      distress (EPDS scores) varied according to MRA level. Women who were categorised
      as high MRA and no longer breast feeding had higher EPDS scores and were more
      likely to be categorised as distressed (36%) than women who had low MRA (<12%) or
      women who had high MRA and continued to breast feed (7%). IMPLICATIONS: There is
      a complex relationship between maternal identity, stopping breast feeding earlier
      than desired, and psychological distress. Women with strong beliefs about the
      importance of breast feeding to their maternal role may benefit from
      psychological assessment and support should they decide to stop breast feeding
      earlier.

PMID- 17011684
TI  - Altered energy dissipation ratio of the plantar soft tissues under the metatarsal
      heads in patients with type 2 diabetes mellitus: a pilot study.
AB  - BACKGROUND: Foot ulceration occurs frequently on the plantar aspect of the
      metatarsal head region, in which the altered foot biomechanics has been mentioned
      as a contributor. This study attempted to compare the energy dissipation in the
      plantar soft tissue under the metatarsal head between type 2 diabetic patients
      and age-matched healthy subjects in vivo. METHODS: The plantar soft tissues under
      the metatarsal heads in each left foot of 13 patients with type 2 diabetes
      mellitus and eight age-matched healthy subjects were measured with a loading
      unloading device. The system comprised a 5-12 MHz linear-array ultrasound
      transducer and a load cell that operated at an impact velocity of about 5 cm/s.
      The stress-strain plot was derived by simultaneously recording the stress
      response and tissue deformation during a loading-unloading cycle. The energy
      dissipation ratio in all subjects could then be analyzed. FINDINGS: Although only
      the plantar soft tissue under the fourth metatarsal head in the diabetic patients
      endured significantly greater energy (P=0.035) than the healthy subjects, a trend
      of an increased energy dissipation ratio for the metatarsals in the diabetic
      patients was observed. INTERPRETATION: The plantar soft tissue under the
      metatarsal head in the diabetic patients endures high dissipated energy during a
      simulating walking status in the study. The increased dissipated energy in the
      tissue may be responsible for the tissue breakdown in the diabetic patients.

PMID- 17011685
TI  - Heavy metal load and dominance hierarchy in juvenile willow tits during winter.
AB  - Possible links between plasma testosterone levels, heavy metal loads and
      dominance in juvenile male willow tits (Parus montanus) are studied during winter
      conditions in Norway. Dominant individuals have better access to food resources,
      significantly higher cadmium content in the liver and higher plasma testosterone
      level compared to subordinates. A positive correlation was also found between
      plasma testosterone level and content of cadmium in the liver. Although the
      results in our study shows only a limited difference in testosterone level of
      dominant and subordinate juvenile male willow tits, possible small changes in
      behaviour might have crucial effects on winter survival of these birds.

PMID- 17011686
TI  - Assessment of the impact of increasing concentrations of ozone on photosynthetic
      components of maize (Zea mays L.), a C4 plant.

PMID- 17011687
TI  - Role of microbial inoculation and chitosan in phytoextraction of Cu, Zn, Pb and
      Cd by Elsholtzia splendens--a field case.
AB  - A field experiment was carried out to study the effect of microbial inoculation
      on heavy metal phytoextraction by Elsholtzia splendens and whether chitosan could
      have a synergistic effect with the microbial inocula. The microbial inocula
      consisted of a consortium of arbuscular mycorrhizal fungi and two Penicillium
      fungi. Three treatments were included: the control, inoculation with microbial
      inocula, and the inoculation combined with chitosan. Microbial inoculation
      increased plant biomass especially shoot dry weight, enhanced shoot Cu, Zn and Pb
      concentrations but did not affect Cd, leading to higher shoot Cu, Zn, Pb and Cd
      uptake. Compared with microbial inoculation alone, chitosan application did not
      affect plant growth but increased shoot Zn, Pb and Cd concentrations except Cu,
      which led to higher phytoextraction efficiencies and partitioning to shoots of
      Zn, Pb and Cd. These results indicated synergistic effects between microbial
      inocula and chitosan on Zn, Pb and Cd phytoextraction.

PMID- 17011688
TI  - Selecting new health technologies for evaluation: can clinical experts predict
      which new anticancer drugs will impact Danish health care?
AB  - Several countries have systems in place to support the managed entry of new
      health technologies. The big challenge for these so-called horizon-scanning
      systems is to select those technologies that require decision support by means of
      an early evaluation. Clinical experts are considered a valuable source of
      information on new health technologies, but research on the relevance of their
      input is scarce. In 2000, we asked six Danish expert oncologists to predict
      whether a sample of 19 new anticancer drugs would impact Danish health care over
      the next 5 years. In 2005, we assessed the accuracy of these predictions in a
      delayed type cross-sectional study. The specificity of the Danish experts'
      prediction was 1 (95% confidence interval 0.74-1.00) and the sensitivity was 0.63
      (0.31-0.86). The negative predictive value was 0.79 (0.52-0.92) and the positive
      predictive value was 1 (0.57-1.00). This indicates that clinical experts have the
      ability to predict which new anticancer drugs are unlikely to have an impact.
      This information can be used to increase the efficiency of selecting new
      technologies for evaluation. As the experts missed 37% of drugs that are in need
      of guidance, they should not be relied upon to select drugs relevant for
      evaluation.

PMID- 17011689
TI  - Low-linking social capital as a predictor of mental disorders: a cohort study of
      4.5 million Swedes.
AB  - Few previous studies have analyzed the association between different dimensions
      of social capital and mental disorders. This study examines whether there is an
      association between a relatively new theoretical concept describing the amount of
      trust between individuals and societal institutions, i.e. linking social capital,
      and hospitalization due to depression or psychosis. The entire Swedish population
      aged 25-64, a total of 4.5 million men and women, was followed from January 1,
      1997, until the first hospital admission due to depression or psychosis during
      the study period, or the end of the study on December 31, 1999. Small area
      neighborhood units were used to define neighborhoods. The definition of linking
      social capital was based on mean voting participation in each neighborhood unit,
      categorized in tertiles. Multilevel logistic regression was used to estimate odds
      ratios and neighborhood-level variance in four different models. The results
      showed strong associations between linking social capital and hospitalization due
      to depression or psychosis. These associations decreased considerably in both men
      and women, but still remained significant, after adjustment for age, housing
      tenure, education, employment status, marital status, and country of birth.
      However, the results for depression (both men and women) no longer remained
      significant after adjustment for neighborhood deprivation. In contrast, the
      results for psychosis decreased considerably but remained significant after
      adjustment for neighborhood deprivation. The association between low levels of
      voting participation and hospitalization due to depression or psychosis might
      reflect neighborhood differences in linking social capital, which could affect
      vulnerable individuals negatively. Decision-makers should take into account the
      evidence of a neighborhood effect on mental health in decisions regarding the
      sites of psychiatric clinics and other kinds of community support for psychiatric
      patients.

PMID- 17011690
TI  - Marital status and mortality in the elderly: a systematic review and meta
      analysis.
AB  - Although a relationship between marital status and mortality has long been
      recognized, no summary estimates of the strength of the association are
      available. A meta-analysis of cohort studies was conducted to produce an overall
      estimate of the excess mortality associated with being unmarried in aged
      individuals as well as to evaluate whether and to what degree the effect of
      marriage differs with respect to gender, geographical/cultural context, type of
      non-married condition and study methodological quality. All included studies were
      published after the year 1994, used multivariate analyses and were written in
      English. Pooling 53 independent comparisons, consisting of more than 250,000
      elderly subjects, the overall relative risk (RR) for married versus non-married
      individuals (including widowed, divorced/separated and never married) was 0.88
      (95% Confidence Interval: 0.85-0.91). This estimate did not vary by gender, study
      quality, or between Europe and North America. Compared to married individuals,
      the widowed had a RR of death of 1.11 (1.08-1.14), divorced/separated 1.16 (1.09
      1.23), never married 1.11 (1.07-1.15). Although some evidence of publication bias
      was found, the overall estimate of the effect of marriage was robust to several
      statistical approaches and sensitivity analyses. When the overall meta-analysis
      was repeated with an extremely conservative approach and including eight non
      significant comparisons, which were initially excluded because of data
      unavailable, the marriage protective influence remained significant, although the
      effect size was reduced (RR=0.94; 0.92-0.95). Despite some methodological and
      conceptual limitations, these findings might be important to support health care
      providers in identifying individuals "at risk" and could be integrated into the
      current programs of mortality risk estimation for the elderly.

PMID- 17011691
TI  - Evaluation of ammonium perchlorate in the endocrine disruptor screening and
      testing program's male pubertal protocol: ability to detect effects on thyroid
      endpoints.
AB  - The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal
      protocol was designed as a screen to detect endocrine-disrupting chemicals which
      may alter reproductive development or thyroid function. One purpose of this in
      vivo screening protocol is to detect thyrotoxicants via a number of different
      mechanisms of action, such as thyroid hormone synthesis or clearance. Here we
      evaluate the ability of this EDSP male pubertal protocol to detect the known
      thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium
      perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and
      lubricants. Over the past 50 years, potassium perchlorate has been used to treat
      hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by
      competitively inhibiting iodide uptake by the thyroid gland. In this study,
      ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male
      Wistar rats based on a pilot study of oral dosing. Doses of 125-500 mg/kg
      perchlorate decreased T4 in a dose-dependent manner. TSH was significantly
      increased in a dose-responsive manner at the same doses, while T3 was unchanged
      at any dose. Thyroid histology was significantly altered at all doses, even at
      the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase
      in follicular cell height. No effects on preputial separation, a marker of
      pubertal progression, or reproductive tract development were observed at any
      dose. These results demonstrate that the male pubertal protocol is useful for
      detecting thyrotoxicants which target the thyroid axis by this mechanism (altered
      uptake of iodide). This study also found that perchlorate exposure during this
      period did not alter any of the reproductive developmental endpoints.

PMID- 17011692
TI  - Neurodynamics of sentence interpretation: ERP evidence from French.
AB  - Sentence interpretation was examined with event-related brain potentials (ERPs).
      The ERPs were recorded while participants listened to French sentences containing
      a subject-modifying relative clause (SRC). These were either correct,
      semantically incorrect, syntactically incorrect, or doubly (syntactically and
      semantically) incorrect. The semantic anomaly realized as a selectional
      restriction violation was associated with an N400. The syntactic anomaly realized
      as a phrase structure violation in the SRC elicited a frontal negativity between
      150 and 600 ms. This negativity was more pronounced in the left than in the right
      hemisphere in the early time window (150-300 ms). In a later time window (300-600
      ms), it was more broadly distributed including anterior and posterior regions,
      but with a maximum over the anterior recording sites. Finally, a centro-parietal
      late positivity (P600) was found between 600 and 1000 ms. While syntactic and
      semantic information in the double violation condition did not interact between
      150 and 300 ms, they did interact between 300 and 600 ms. This finding supports
      serial models of sentence processing that postulate an initial autonomous stage
      of phrase structure building and a late stage of interaction.

PMID- 17011693
TI  - Poor sleep the night before an experimental stress task is associated with
      reduced cortisol reactivity in healthy women.
AB  - Sleep disruption is a growing problem that may have serious health effects. As
      stress-induced increases in cortisol are thought to be a key adaptive process it
      is important to examine how this response is affected by sleep. The current study
      investigated the association of four sleep parameters (objective/subjectively
      measured sleep quality and quantity) and subsequent salivary cortisol reactivity
      (maximal change from baseline) to an experimental stressor in 53 healthy women.
      Objective actigraphy monitoring and self-report diaries were used to assess
      sleep. Results revealed that individuals with lower objective sleep quality (wake
      percentage during sleep) had a blunted response to the experimental stressor. No
      associations were found between cortisol reactivity and actigraphy-derived sleep
      quantity, or either of the self-reported sleep variables. Results are discussed
      with regard to the possible adverse health effects that may result from poor
      sleep quality and a blunted cortisol response to stress.

PMID- 17011694
TI  - Relationship between serum human chorionic gonadotrophin levels and body mass
      index in women undergoing in vitro fertilisation cycles.
AB  - OBJECTIVE: To ascertain if serum concentrations following injection of human
      chorionic gonadotropin (hCG) influenced the outcome of in vitro fertilisation
      (IVF) treatment and correlated to body mass index (BMI). STUDY DESIGN: A
      prospective study conducted with the participation of 149 women undergoing IVF
      and/or intracytoplasmic sperm injection (ICSI) treatment at the regional IVF Unit
      in Liverpool, UK. The BMI of each individual was calculated and serum hCG
      concentrations were measured at 12 and 36 h following a subcutaneously (SC)
      injection of 5000 IU hCG. The main outcome measures were fertilisation rate and
      biochemical pregnancy rate. RESULTS: No correlation was found between serum hCG
      levels at 12 and 36 h with the number of oocytes retrieved or the number of
      oocytes fertilised. Furthermore, there was no correlation between BMI and hCG
      levels at 12 and 36 h following administration (Pearson's correlation
      coefficient: -0.23, -0.24, respectively). CONCLUSION: Our results suggest that
      the serum concentrations of hCG do not influence IVF outcome and that the serum
      levels of hCG achieved following administration do not correlate with the
      individual's BMI. Serum hCG concentration also does not correlate with number of
      oocytes collected or fertilisation rate.

PMID- 17011695
TI  - Congenital chloride diarrhea in pregnancy: A case report.

PMID- 17011696
TI  - White blood cell count as a predictor of the severity of sickle cell disease
      during pregnancy.
AB  - OBJECTIVE: Increasing epidemiological evidence implicates leukocytosis as a major
      risk factor for poor outcome in non-pregnant sickle cell disease (SCD) patients.
      The aim of this study was to investigate whether steady-state white blood cell
      (WBC) count can predict SCD-related problems in pregnancy. DESIGN: Retrospective
      observational study of 40 SCD pregnant women who had their antenatal care at
      Guy's & St Thomas' NHS Trust, London. Twenty-six women developed clinical
      complications related to SCD during their pregnancy (painful crisis, chest
      symptoms, infections, severe anaemia requiring blood transfusion, pre-eclampsia,
      and/or thromboembolism) and 14 remained asymptomatic. The steady-state leukocyte
      counts early in pregnancy were compared between the two groups and receiver
      operator characteristics (ROC) curve was plotted for different values of WBC.
      RESULTS: Compared to asymptomatic patients, women who developed SCD-related
      complications had significantly higher total WBC count [11.2 x 10(9)L(-1) (SD
      3.22) versus 8 x 10(9)L(-1) (2.8), p<0.01], higher lymphocyte count [3 x 10(9)L(
      1) (1.62) versus 1.6 x 10(9)L(-1) (0.65), p<0.01] and higher monocyte count [0.8
      x 10(9)L(-1) (0.47) versus 0.4 x 10(9)L(-1) (0.21), p<0.01]. The neutrophil count
      showed a similar trend but the difference did not reach statistical significance
      [6.6 x 10(9)L(-1) (2.29) versus 5.7 x 10(9)L(-1) (2.15), p=0.22]. The area under
      the ROC curve was 74% (95% CI: 56-92). CONCLUSION: WBC count early in pregnancy
      was significantly higher in women who subsequently developed clinical problems
      related to SCD. The WBC may be used as a predictor of the severity of SCD in
      pregnancy.

PMID- 17011697
TI  - Changes in binding of hydrogen ions in enzyme-catalyzed reactions.
AB  - Most enzyme-catalyzed reactions produce or consume hydrogen ions, and this is
      expressed by the change in the binding of hydrogen ions in the biochemical
      reaction, as written in terms of reactants (sums of species). This property of a
      biochemical reaction is important because it determines the change in the
      apparent equilibrium constant K' with pH. This property is also important because
      it is the number of moles of hydrogen ions that can be produced by a biochemical
      reaction for passage through a membrane, or can be accepted from a transfer
      through a membrane. There are two ways to calculate the change in binding of
      hydrogen ions for an enzyme-catalyzed reaction. The first, which has been used
      for a long time, involves calculating the partial derivative of the standard
      transformed Gibbs energy of reaction with respect to pH. The second involves
      calculating the average numbers of hydrogen ions in each reactant and adding and
      subtracting these average numbers. The changes in binding of hydrogen ions
      calculated by the second method at pHs 5, 6, 7, 8, and 9 are given for 23 enzyme
      catalyzed reactions. Values are given for 206 more reactions on the web. This
      database can be extended to include more reactions for which pKs of reactants are
      known or can be estimated.

PMID- 17011698
TI  - Switching mechanism for branched biochemical fluxes: graph-theoretical analysis.
AB  - A graph-theoretical method is applied to characterize the structure of a simplest
      switching mechanism of common biochemical importance. This mechanism is based on
      competition of two coupled substrate-binding pathways for a single substrate. No
      other regulatory interactions are shown to be needed for the switching phenomenon
      to be observed. It is shown that switch in branch effluxes is observed as
      bistability or reciprocal oscillations, depending on the value of steady influx.
      Frequency of reciprocal efflux oscillations in branches is regulated by steady
      influx. Therefore, the switching mechanism can function as the coding mechanism
      in the manner of "influx steady level-efflux frequency". The calculated kinetic
      equations for the switching mechanism demonstrate very steep transitions in the
      branch fluxes without using high non-linearity of these equations.

PMID- 17011699
TI  - Must colposuspension be associated with sacropexy to prevent postoperative
      urinary incontinence?
AB  - OBJECTIVES: This prospective, randomised study investigated whether a
      prophylactic procedure, performed during colposacropexy for prolapse repair,
      prevents ex novo postoperative incontinence. Sixty-six consecutive continent
      patients with advanced prolapse were randomised into two groups: group A
      underwent sacropexy combined with a Burch colposuspension; no anti-incontinence
      procedure was performed in group B patients. METHODS: Work-up included clinical
      assessment (Halfway System and International Continence Society [ICS]
      classification for prolapse and Ingelman Sunderberg scale for incontinence), the
      Urogenital Distress Inventory and Impact Incontinence Quality of Life
      questionnaires, urogynaecologic ultrasound scans, and complete urodynamic testing
      that included the urethral pressure profile and Valsalva leak point pressure with
      reduced prolapse. Check-ups were done at 3, 6, 12 mo postoperatively and then
      yearly. Mean follow-up time was 39.5 mo. RESULTS: The mean age (+/- standard
      deviation) was 62+/-9 yr. All patients presented with grade (G) 3-4 prolapse.
      Postoperative incontinence was present in 12 of the 34 patients in group A: 7 G1;
      4 G2, and 1 G3. Postoperative incontinence was present in 3 of the 32 patients in
      group B: 2 G1, 1 G3. The frequency of postoperative incontinence was
      significantly greater in patients who had undergone colposuspension (p<0.05).
      CONCLUSIONS: These preliminary data cast doubt on whether colposuspension should
      be performed during sacropexy for severe urogenital prolapse as prophylaxis for
      postoperative incontinence because it seems to emerge as overtreatment.
      Incontinence developed ex novo in 35% of continent patients treated with
      colposuspension combined with sacropexy.

PMID- 17011700
TI  - Modeling the regulation of the competence-evoking quorum sensing network in
      Streptococcus pneumoniae.
AB  - Competence for genetic transformation seems to play a fundamental role in the
      biology of Streptococcus pneumoniae and is believed to account for serotype
      switching, evolution of virulence factors, and rapid emergence of antibiotic
      resistance. The initiation of competence is regulated by the quorum sensing
      system referred as the ComABCDE pathway. Experimental studies reveal that
      competence is down-regulated a short time after its induction and several
      hypotheses about the mechanism(s) responsible for this shut-down have been
      presented. Possibly, a ComX-dependent gene product, such as a repressor or a
      phosphatase, is involved. To better understand the down-regulation of the
      competence-evoking system in S. pneumoniae, a mathematical model was set up. By
      analyzing the model, we suggest that shut-down of competence possibly occurs at
      the transcriptional level on the comCDE operon. As a result of introducing a
      putative comX-dependent repressor, which inhibits expression of comCDE and comX,
      in the mathematical model, competence is demonstrated to appear in waves. This is
      supported by experimental studies showing the appearance of successive competence
      cycles in pneumococcal batch cultures.

PMID- 17011701
TI  - A design framework to model retinas.
AB  - Neuro-engineering is providing biomedical engineers with technology to interface
      the nervous system, which is useful to create prosthetic devices to palliate
      sensorial or motor disabilities. Motivated by the success of cochlear implants
      for deaf patients, we are now facing the challenge of creating a prosthetic
      visual system for the blind. An artificial retina whose response to stimuli can
      be matched to biological ones is required. To make easier the task of modeling,
      tuning and testing these retinal models, we have created a software tool that
      allows flexible and parametric definition and testing of retina-like models. The
      program can be fed with a variety of video or image sources, and the results can
      be easily compared to biological recordings of retinal ganglionar activity in
      response to the same stimuli. This tool can be useful, not only for this
      prosthetic purpose, but for any other research involving bio-inspired image
      processing with a neuromorphic output.

PMID- 17011702
TI  - A naturally occurring mutation in the human androgen receptor of a subject with
      complete androgen insensitivity confers binding and transactivation by estradiol.
AB  - The clinical phenotype of complete androgen insensitivity (CAIS) was associated
      with a mutation in the human androgen receptor (hAR) gene encoding the amino acid
      substitution, M745I, in the hAR protein. Transcriptional activation of hAR(M745I)
      by the synthetic androgen, methyltrienolone (R1881), was reduced compared to wild
      type (wt) hAR. The transcriptional co-activator, androgen receptor associated
      protein 70 (ARA70), failed to enhance transactivation of hAR(M745I) at lower
      concentrations of R1881 (0.01-0.1 nM), whereas the p160 co-activators, SRC-1 and
      TIF2, stimulated activity. Transcriptional activity of hAR(M745I) was stimulated
      by 1 or 10 nM R1881 and activity was further enhanced by co-expression of ARA70
      similar to that of the hAR(wt). Transcriptional activity of hAR(wt) was minimally
      stimulated by estradiol (E2) without or with co-expression of ARA70, whereas 10
      or 100 nM E2 increased transactivation by hAR(M745I) of the androgen-responsive
      MMTV-luciferase reporter gene by 10-fold and activity was further enhanced by
      ARA70. Increasing concentrations of E2 competed more effectively for binding of
      R1881 to hAR(M745I) than to hAR(wt), indicative of the preferential binding of E2
      to the mutant hAR. Partial tryptic digestion of hAR wt and M745I revealed that
      activation of the mutant protein was reduced in the presence of R1881. By
      contrast, tryptic digestion showed that the mutant hAR was activated by the
      binding of E2. In conclusion, the clinical phenotype of CAIS resulted from a hAR
      gene mutation encoding hAR(M745I) with reduced binding and transactivation by
      androgens, but the novel properties of enhanced affinity for and increased
      transactivation by estradiol.

PMID- 17011703
TI  - Significant linkage and association between a functional (GT)n polymorphism in
      promoter of the N-methyl-D-aspartate receptor subunit gene (GRIN2A) and
      schizophrenia.
AB  - Dysfunction of the N-methyl-d-aspartate (NMDA) type glutamate receptor has been
      proposed as a mechanism in the etiology of schizophrenia, based on the
      observation that non-competitive antagonists of the NMDA receptor, such as
      phencyclidine, induce schizophrenia-like symptoms. Previous study identified a
      variable (GT)n polymorphism in the promoter region of the N-methyl-d-aspartate
      (NMDA) subunit gene (GRIN2A), and showed its association with schizophrenia in a
      case-control study, together with a correlation between the length of the repeat
      and severity of chronic outcome. Our present study was aimed at confirming the
      association of the (GT)n polymorphism of GRIN2A promoter with schizophrenia using
      122 Han Chinese sib-pair families. Non-parametric linkage analysis and
      transmission/disequilibrium test (TDT) were undertaken using the GENEHUNTER,
      v2.1. In non-parametric linkage analysis, suggestive linkage was found for the
      (GT)n polymorphism (NPL=2.77, P=0.002902). The TDT was significant for (GT)n
      polymorphism and that the (GT)23 was preferentially transmitted to schizophrenia
      affected children (T/NT: 123:72, chi(2)=13.34, P=0.000260). Our results indicate
      that the (GT)n polymorphism in the promoter of GRIN2A gene may play a significant
      role in the etiology of schizophrenia among our samples.

PMID- 17011704
TI  - Somatotopic organization of the processing of muscle and cutaneous pain in the
      left and right insula cortex: a single-trial fMRI study.
AB  - The insula is involved in processing noxious information. It is consistently
      activated by acute noxious stimuli, can elicit pain on stimulation, and lesions
      encompassing the insula can alter pain perception. Anatomical tracing,
      electrophysiological and functional brain imaging investigations have suggested
      that the insula is somatotopically organized with respect to noxious cutaneous
      inputs. It has also recently been revealed that the anterior insula displays
      differential activation during cutaneous compared with muscle pain. Given this
      difference, it is important to determine if an insula somatotopy also exists for
      muscle pain. Using high-resolution functional magnetic resonance imaging (fMRI)
      we compared insula activation patterns in 23 subjects during muscle and cutaneous
      pain induced in the right leg and forearm. Group and frequency analyses revealed
      somatotopically organized signal increases in the posterior contralateral (left)
      and ipsilateral (right) anterior insula. Within the posterior contralateral
      insula, signal increases during both cutaneous and muscle forearm pain were
      located lateral and anterior to those evoked by leg pain, whereas in the
      ipsilateral anterior insula the pattern was reversed. Furthermore, within the
      ipsilateral anterior insula, muscle pain activated a region anterior to that
      activated by cutaneous pain. This somatotopic organization may be crucial for
      pain localization or other aspects of the pain experience that differ depending
      on both stimulation site and type of tissue activated. This study reveals that
      the insula is organized somatopically with respect to muscle and cutaneous pain
      and that this organization is further separated according to the tissue in which
      the pain originates.

PMID- 17011705
TI  - Sensorimotor integration in Complex Regional Pain Syndrome: a transcranial
      magnetic stimulation study.
AB  - There is evidence that patients with Complex Regional Pain Syndrome (CRPS) have
      altered central sensorimotor processing. Sensory input can influence motor output
      either through indirect pathways or through direct connections from the sensory
      to motor cortex. The purpose of this study was to investigate sensorimotor
      interaction via direct connections in patients with CRPS and to compare the
      results with normal subjects'. Direct short-latency sensory-motor interaction was
      evaluated in eight patients with CRPS1 affecting a hand. Modulation of EMG
      responses to transcranial magnetic stimulation (TMS) induced by concomitant
      median nerve stimulation was measured, the so-called, short-latency afferent
      inhibition (SAI). Results were compared with eight normal subjects who were age
      and sex matched with the patients. As expected, all the normal subjects' EMG
      responses to TMS with median nerve stimulation were smaller than responses to TMS
      alone. In seven of the eight CRPS patients EMG responses to TMS were suppressed
      when paired with median nerve stimulation. Only one CRPS patient's results showed
      no suppression of EMG responses. These results suggest that the disease
      mechanisms of CRPS1 do not typically affect the direct neural circuit between
      sensory and motor cortex and that normal sensorimotor interaction is occurring
      via this route.

PMID- 17011706
TI  - Pain-related catastrophizing and perceived social responses: Inter-relationships
      in the context of chronic pain.
AB  - Pain-related coping, particularly catastrophizing, plays a significant role in
      shaping pain responses. One way catastrophizing is hypothesized to amplify pain
      and disability is via its effect on patients' social environments (e.g., communal
      coping model), though empirical support is limited. The present study tested
      whether the association between catastrophizing and deleterious pain-related
      outcomes was mediated by patients' perceptions of significant others' responses
      to their pain in a sample of 1356 pain patients. Regression analyses showed that
      perceived significant other punishing responses partially mediated
      catastrophizing's relationship with pain-related disability, and with depressive
      symptoms. Further, several variables moderated the association between
      catastrophizing and perceived social responses to pain. Catastrophizing was more
      strongly associated with greater perceived solicitous responses for patients of
      relatively short pain duration. Also, higher catastrophizing was more strongly
      associated with perceived punishing responses among patients perceiving lower
      social support. In addition, the mediational effects of perceived punishing
      responses on catastrophizing's relationship with depressive symptoms, and with
      pain-related disability were only found in individuals reporting low levels of
      perceived social support. In sum, perceived social responses were found to play a
      small role in mediating the relationship between catastrophizing and pain-related
      outcomes, and these mediational effects may be strongest in particular patient
      subgroups. The present data suggest that interpersonal mechanisms may not
      constitute a primary route by which catastrophizing exerts its maladaptive
      effects on pain responses. The study and further understanding of what principal
      factors mediate catastrophizing's deleterious effects on pain will be important
      in illuminating the biopsychosocial model of pain.

PMID- 17011707
TI  - Long-term alteration of pain sensitivity in school-aged children with early pain
      experiences.
AB  - While animal studies suggest that neonatal pain experiences induce long-term
      alterations in pain sensitivity, no such data exist in humans. Changes in pain
      sensitivity in school-aged children (9-14 years) who were born preterm or
      fullterm, had been hospitalized for a prolonged period of time after birth and
      had undergone repeated painful procedures while being treated in a Neonatal
      Intensive Care Unit (NICU) were determined. A retrospective cohort study of 19
      preterm (<or=31 weeks gestational age) and 20 fullterm children (>or=37 weeks
      gestational age) treated at least 3 days in a NICU at a University Hospital and
      20 fullterm control children without NICU experience was performed. Perceptual
      sensitization to tonic heat and repetitive mechanical stimuli as well as heat
      pain and mechanical pain thresholds were obtained at the thenar and a trigeminal
      site. Length of hospitalization and NICU treatment was significantly higher in
      preterm than fullterm children. Nonetheless, both preterm and fullterm children
      with NICU experience showed greater perceptual sensitization to tonic heat and
      elevated heat pain thresholds at both sites. Mechanical pain threshold and
      perceptual sensitization did not differ between groups. Consistent with findings
      in animals, repeated pain experiences during the neonatal period were associated
      with alterations in thermal pain responsivity in school-aged preterm and fullterm
      children that was characterized by enhanced perceptual sensitization to prolonged
      painful stimulation and hypoalgesia to brief heat pain stimuli. Our findings
      suggest that repeated pain experiences in neonates may induce activity-induced
      changes in the functioning of pain pathways that persist well beyond infancy.

PMID- 17011708
TI  - Carbon nanotubes: a promising standard for quantitative evaluation of AFM tip
      apex geometry.
AB  - The direct contact between tip and sample in atomic force microscopy (AFM) leads
      to demand for a quantitative knowledge of the AFM tip apex geometry in high
      resolution AFM imaging and many other types of AFM applications like force
      measurements and surface roughness measurements. Given, the AFM tip apex may
      change continuously during measurements due to wear or during storage due to
      oxidation, it is very desirable to develop an easy and quick way for quantitative
      evaluation of AFM tip radius when necessary. In this study, we present an
      efficient method based on Zenhausern model (Scanning 14 (1992) 212) by measuring
      single-wall carbon nanotubes deposited on a flat substrate to reach this goal.
      Experimental results show the method can be used for routine quantitative
      evaluation of AFM tip apex geometry for tips with effective radii down to the
      nanometer scale.

PMID- 17011709
TI  - The serum glucose and beta-hydroxybutyrate levels in sheep with experimental
      Fasciola hepatica and Fasciola gigantica infection.
AB  - The influence of Fasciola hepatica and Fasciola gigantica infection on serum
      glucose and beta-hydroxybutyrate (beta-HOB) in sheep was evaluated. This was done
      by setting up two groups of sheep. The first group (n=13) was split in two sub
      groups, one experimentally infected with F. hepatica (n=9) and the other (n=4) as
      uninfected control. A second group consisting of a sub-group experimentally
      infected with F. gigantica (n=9) the other sub-group (n=6) left as uninfected
      control was also set up. The results of weight gain, parasitological and serum
      liver enzymes activity (glutamate dehydrogenase [GLDH] and gamma
      glutamyltransferase [gamma-GT]) used in monitoring the infection showed that all
      infected animals developed fasciolosis. It was observed that a reduction in serum
      glucose levels was significantly lower (p<0.05) in F. hepatica infected sheep
      than in uninfected control sheep starting from 5 weeks post-infection (wpi) to
      the end of the experiment. Similar reduction was recorded in F. gigantica
      infected sheep between 8 and 19 wpi. In contrast, serum beta-HOB levels were
      elevated in F. hepatica infected sheep between 6 and 16 wpi and in F. gigantica
      infected sheep between 7 and 15 wpi. It would appear from these serum glucose and
      beta-HOB levels that fasciolosis does lead to energy deficiency (low glucose) and
      ketosis (increased beta-HOB). The decrease in serum glucose and increase in serum
      beta-HOB levels in infected sheep may help in understanding the interaction
      between fasciolosis and nutritional status of infected ruminants especially in
      young growing animals.

PMID- 17011710
TI  - Expression of aggrecan(ases) during murine preadipocyte differentiation and
      adipose tissue development.
AB  - The expression and potential functional role of aggrecan in adipogenesis and
      adipose tissue development was investigated in murine models of obesity.
      Aggrecan, as well as the two aggrecanases ADAMTS-4 and ADAMTS-5 (A Disintegrin
      And Metalloproteinase with Thrombospondin motif) mRNAs, are expressed in
      subcutaneous (SC) and gonadal (GON) adipose tissues of mice. Their presence was
      confirmed by western blotting using adipose tissue extracts. In mice with
      nutritionally induced obesity (high fat diet) as well as in lean controls,
      aggrecan mRNA expression was downregulated whereas ADAMTS-4 and ADAMTS-5 were
      upregulated with time. In mice with genetically determined obesity (ob/ob),
      ADAMTS-5 mRNA was upregulated in both SC and GON adipose tissues, as compared to
      wild-type (WT) mice (p<0.001). Enhanced aggrecanase expression levels in these
      tissues were associated with significantly elevated levels of G1-NITEGE, a
      degradation product of aggrecan. Thus, aggrecan levels were high at the early
      stages of adipose tissue development in mice, whereas its production decreased
      and its degradation increased during development of obesity. A functional role of
      aggrecan in promoting early stages of adipogenesis is supported by the findings
      that it stimulated the in vitro differentiation of 3T3-F442A preadipocytes and
      the de novo in vivo accumulation of fat in Matrigel plaques injected into WT
      mice. Proteoglycans in the extracellular matrix of adipose tissue, such as
      aggrecan, may contribute to the regulation of lipid uptake and obesity in mice.

PMID- 17011711
TI  - Influence of silymarin and its flavonolignans on H(2)O(2)-induced oxidative
      stress in human keratinocytes and mouse fibroblasts.
AB  - The administration of antioxidants has been shown to enhance repair and healing
      processes in cutaneous tissue. Silymarin, an extract from Silybum marianum has
      been reported to be beneficial in the treatment of chemically-induced oxidative
      stress in mouse. In this study, we investigated the protective effects of
      silymarin, its flavonolignans silybin and dehydrosilybin and flavonoids quercetin
      and taxifolin against hydrogen peroxide-induced damage to human keratinocytes and
      mouse fibroblasts. The results showed that the cytotoxicity of hydrogen peroxide
      was dose-dependent in both cell lines. Pre-treatment with test compounds
      decreased oxidative injury. Dehydrosilybin and quercetin were the most powerful
      protectants. Silymarin was comparable to silybinin, its main component. This
      correlates with the antioxidant potential of the compounds. Our findings suggest
      that silymarin, flavonolignans and flavonoids may be useful as agents for
      improving skin tissue regeneration.

PMID- 17011713
TI  - Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma
      hydroxybutyrate (GHB)?
AB  - Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet
      with feelings of well-being and mild euphoria. These feelings have often been
      attributed to ketosis, the production of ketone bodies which can replace glucose
      as an energy source for the brain. One of these ketone bodies, beta
      hydroxybutyrate (BHB), is an isomer of the notorious drug of abuse, GHB (gamma
      hydroxybutyrate). GHB is also of interest in relation to its potential as a
      treatment for alcohol and opiate dependence and narcolepsy-associated cataplexy.
      Here I hypothesize that, the mild euphoria often noted with fasting or low
      carbohydrate diets may be due to shared actions of BHB and GHB on the brain.
      Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak
      partial agonist for GABA(B) receptors. I outline several approaches that would
      test the hypothesis, including receptor binding studies in cultured cells,
      perception studies in trained rodents, and psychometric testing and functional
      magnetic resonance imaging in humans. These and other studies investigating
      whether BHB and GHB share common effects on brain chemistry and mood are timely
      and warranted, especially when considering their structural similarities and the
      popularity of ketogenic diets and GHB as a drug of abuse.

PMID- 17011712
TI  - The reinforcing, subject-rated, performance, and cardiovascular effects of d
      amphetamine: influence of sensation-seeking status.
AB  - Individual differences that may contribute to vulnerability to abuse drugs have
      been identified. Sensation-seeking status has been shown to influence both
      vulnerability to drug use and response to acute drug administration. The purpose
      of the present experiment was to examine the reinforcing effects of d-amphetamine
      in high and low sensation-seeking subjects using a modified progressive-ratio
      procedure. A battery of subject-rated, performance, and cardiovascular measures
      was also included to better characterize the effects of d-amphetamine in these
      groups. Ten high sensation seekers and ten low sensation seekers that were
      matched for education, age, drug use, height, and weight, first sampled doses of
      d-amphetamine (0, 8, and 16 mg). In subsequent sessions, subjects were offered
      the opportunity to work for the sampled dose on a modified progressive-ratio
      procedure. d-Amphetamine functioned as a reinforcer and produced prototypical
      stimulant-like effects (e.g., increased subject-ratings of Like Drug, enhanced
      performance, and increased heart rate). High sensation seekers were more
      sensitive than low sensation seekers to the reinforcing and some of the subject
      rated effects of d-amphetamine. The results of the present experiment extend
      those of previous findings by demonstrating that the reinforcing effects of d
      amphetamine vary as a function of the biologically based sensation-seeking
      personality trait. These results suggest that increased stimulant drug use and
      abuse among high sensation seekers may be related, in part, to increased
      sensitivity to the reinforcing effects of stimulants among these individuals.

PMID- 17011714
TI  - Suicide triggers as sex-specific threats in domains of evolutionary import:
      negative correlation between global male-to-female suicide ratios and average per
      capita gross national income.
AB  - From an evolutionary perspective, suicide is a paradoxical phenomenon given its
      fatal consequences on one's reproductive fitness. That fact notwithstanding,
      evolutionists have typically used kin and group selection arguments in proposing
      that suicide might indeed be viewed as an adaptive behavioral response. The
      current paper posits that in some instances, suicide might be construed as the
      ultimate maladaptive response to "crushing defeats" in domains of great
      evolutionary import (e.g., mating). Specifically, it is hypothesized that
      numerous sex-specific triggers of suicide are universally consistent because they
      correspond to dire sex-specific attacks on one's reproductive fitness (e.g., loss
      of occupational status is much more strongly linked to male suicides). More
      generally, it is proposed that many epidemiological aspects of suicide are
      congruent with Darwinian-based frameworks. These include the near-universal
      finding that men are much more likely to commit suicide (sexual selection
      theory), the differential motives that drive men and women to commit suicide
      (evolutionary psychology), and the shifting patterns of suicide across the life
      span (life-history theory). Using data from the World Health Organization and the
      World Bank, several evolutionary-informed hypotheses, regarding the correlation
      between male-to-female suicide ratios and average per capita Gross National
      Income, are empirically tested. Overall, the findings are congruent with
      Darwinian-based expectations namely as economic conditions worsen the male-to
      female suicide ratio is exacerbated, with the negative correlation being the
      strongest for the "working age" brackets. The hypothesized evolutionary outlook
      provides a consilient framework in comprehending universal sex-specific triggers
      of suicide. Furthermore, it allows suicidologists to explore new research avenues
      that might remain otherwise untapped if one were to restrict their research
      interests on the identification of proximate causes of suicide. Global clinical
      and epidemiological data emphasizing other universally robust triggers of suicide
      would afford additional support for the postulated framework.

PMID- 17011715
TI  - Calcific aortic valve disease should not be considered as a degenerative disease
      anymore.
AB  - Calcific aortic valve disease is common among the elderly. Until recently, the
      concept that calcific aortic valve disease is a degenerative and unmodifiable
      process basically induced by long-lasting mechanical stress was generally
      accepted. However calcific aortic valve disease is not merely related to age
      associated "wear and tear". The development and progression of calcific aortic
      valve disease are based on an active process that shares a number of similarities
      with atherosclerosis. Statins and angiotensin-converting enzyme inhibitors have
      been shown to slow calcium accumulation in aortic valves. Thus, calcific aortic
      valve disease should not be considered as a degenerative disease anymore.

PMID- 17011716
TI  - Injection of vitreous body to the Joint Space may be an Alternative Treatment for
      Degenerative Joint Disorders, New Idea.

PMID- 17011717
TI  - Revival of nifedipine, a dihydropyridine-based calcium blocker.
AB  - A recent analysis by the Blood Pressure Lowering Treatment Trialists'
      Collaboration revealed that any commonly-used blood pressure (BP)-lowering
      regimen reduced the risk of total major cardiovascular events, and larger
      reductions in BP produced larger reductions in the risk. These observations
      suggest that most of the differences among treatment regimens in their effects on
      cardiovascular outcomes could be explained by the differences in achieved BP
      level. However, it may also be true that some treatment regimen is superior or
      inferior to others with regard to the risk reduction of cardiovascular events.
      Indeed, the data from dihydropyridine-based calcium antagonist (DHP) trails are
      consistent in that they could not protect against new-onset heart failure or
      progression of renal disease in patients with left-ventricular systolic
      dysfunction or overt proteinuria, respectively. However, a multicenter,
      randomized, placebo-controlled, double-blind ACTION trial, which compared the
      effect of long-acting nifedipine or placebo on mortality and cardiovascular
      morbidity in patients with stable angina, revealed that nifedipine reduced the
      risk for new-onset overt heart failure by 29%. Further, an open-label, randomized
      prospective J-MIND trial, which compared the effect of long-acting nifedipine or
      enalapril, an angiotensin-converting enzyme inhibitor on onset and progression of
      nephropathy in hypertensive patients with type 2 diabetes, showed that long
      acting nifedipine had an equipotent reoprotective effect on diabetic nephropathy.
      In this paper, we would like to propose our hypothesis that nifedipine may be
      unique and superior in its effects on heart failure and proteinuria compared with
      various DHPs. For ensuring our hypothesis, the following clinical issues would be
      addressed. Does nifedipine treatment alone decrease the progression of renal
      disease with overt proteinuria? If these answers are yes, are these beneficial
      effects of nifedipine superior to that of other DHPs with equihypotensive
      properties? Does nifedipine treatment also reduce oxidative stress markers? Are
      these unique effects of nifedipine correlated with its anti-oxidative properties?
      These prospective studies will provide further valuable information whether
      nifedipine may be a preferred DHP to achieve BP goals in hypertensive patients
      with systolic dysfunction or overt proteinuria.

PMID- 17011718
TI  - Celiac sprue is primarily a disease of blocked cellular recognition.
AB  - A key initial event is proposed for the pathogenesis of celiac sprue. The
      indigestible fragments generated from gluten are actively transported to the
      vicinity of sites which are critical for recognition of intestinal basement
      membrane by enterocytes. The fragments are attached in the vicinity of those
      sites by transamidation and make the recognition sites unavailable. Enterocytes
      are lost because they do not recognize that they are in the right place.
      Proliferation in the crypts of Lieberkuhn and immune reactions in the epithelium
      are normal and appropriate. This hypothesis is shown to be compatible with a
      variety of observations, some of which are difficult to explain otherwise.
      Absence of a good animal model is laid to the sensitive site being a human
      peculiarity. The pattern of damage and the fact of recovery on a gluten-free diet
      are explained since the immune reactions and tissue remodeling observed are
      normal responses to tissue damage.

PMID- 17011719
TI  - Why are immigrants at increased risk for psychosis? Vitamin D insufficiency,
      epigenetic mechanisms, or both?
AB  - European researchers have observed that schizophrenia is 3 times more frequent in
      immigrants than in native-born subjects. This increased risk is even higher in
      dark-skinned immigrants, and the second generation is more affected than the
      first one. Immigrant status is an important environmental risk factor not only
      for schizophrenia but also for other psychoses. The explanations proposed to date
      have been mainly related to epidemiological biases and psychological reasons,
      such as racism or social defeat, but no biological hypotheses have been tested so
      far. This article proposes two biological hypotheses related to changes in sun
      exposure, changes in diet, and stress associated with immigration, which would
      explain the increased risk for psychosis associated with immigrant status. (1)
      Vitamin D insufficiency has been proposed as a risk factor for schizophrenia. The
      main source of vitamin D is through photosynthesis by sun exposure, and dark
      skins need more sun exposure to maintain adequate blood levels. Vitamin D
      insufficiency in adulthood could explain why dark-skinned immigrants develop
      psychosis when moving to high latitude countries, and its insufficiency during
      pregnancy could explain why the observed risk is higher in the second generation.
      (2) The second hypothesis is that of epigenetics, with psychosis resulting from
      modifications in gene expression caused by changes in diet and/or stress related
      to immigration. The role of homocysteine and the vitamin B-complex, especially
      folic acid, in these changes in DNA transcription would vary according to the
      polymorphism of the methylenetetrahydrofolate reductase gene. The vitamin D
      insufficiency and epigenetics hypotheses are consistent with yet unexplained
      findings well known in the epidemiology of schizophrenia, such as the increased
      risk in the urban environment, the excess of winter births, the excess of
      schizophrenia births after maternal famine, and the shorter interbirth period
      before a schizophrenia birth. In order to test these hypotheses, epidemiological
      studies of psychosis and immigration should include objective measures of skin
      color, which is predicted to be a more important risk factor than ethnicity. They
      should measure vitamin D, homocysteine and vitamin B-complex status and assess
      the polymorphisms of the vitamin D receptors and the methylenetetrahydrofolate
      reductase gene. If confirmed, these hypotheses would lead to effective and
      inexpensive preventive measures which would markedly decrease the rates of
      psychosis and schizophrenia, as well as the burden and stigma of these diseases,
      and greatly improve the mental health of immigrants.

PMID- 17011720
TI  - Does 'non-chaotic' weight bearing foci cause foot ulcerations in diabetics?

PMID- 17011721
TI  - Does hypocalcemia trigger pulmonary embolism?

PMID- 17011722
TI  - Glucose-6-phosphate-dehydrogenase deficiency is a possible predisposer to Th2
      dominant disorders.

PMID- 17011723
TI  - Change in blood chemistry may explain higher toxicity of total body irradiation
      for bone marrow transplantation.
AB  - Total body irradiation (TBI) is a well established conditioning regimen for
      patients who had undergone bone marrow transplantation. TBI not only offers a
      slightly significant survival advantage over Busulphan-based conditioning
      regimens but also lower toxicity profile. However the biological process after
      TBI seems rather different than conventional routine partial body irradiation.
      Not only the tolerance doses but also time to occurrence of the organ toxicities
      show a variation. It has been shown that there are alterations in trace element
      content in kidney after TBI in addition to cytokines and redox-active metal
      composition of blood. Acute phase proteins also have been shown to rise after
      irradiation. Considering all these evidences we suggest that TBI changes the
      blood content of trace elements, acute phase response proteins with probably many
      other inflammatory proteins and cytokines within the blood and this change in
      blood content may sensitize the organs to radiation.

PMID- 17011724
TI  - Significant transcriptional down-regulation of the human MDR1 gene by beta
      naphthoflavone: a proposed hypothesis linking potent CYP gene induction to MDR1
      inhibition.
AB  - Previous work has established the existence of a co-ordinate response in
      induction between Phase I xenobiotic metabolism, cytochrome P450 (CYP) and the
      multidrug resistance (MDR1) genes in hepatocytes and some tumor cells. Further
      correlation was obtained between development of multidrug resistance in cancer
      cells and a concomitant decrease in inducibility of CYP1A and CYP3A drug
      metabolizing genes. In the present study, a human MDR1 promoter reporter gene
      construct was designed to investigate the reverse effect in which selected
      activators of the major CYP (1-3) genes were tested for potential inhibition of
      transcriptional activity of the MDR1 gene. beta-naphthoflavone (BNF), a potent
      CYP1A1 inducer, significantly (P<0.05) down-regulated MDR1 transcriptional
      activity at 10 microM concentration, causing a 33-fold decrease relative to
      vector control values. Chemotherapeutic relevance of BNF's transcriptional down
      regulation of MDR1 promoter activity was further demonstrated by its restoring
      45.86%, and 79.34% drug sensitivity to the resistant MCF-7/Adr cells at 10- and
      20 microM concentrations, respectively (P<0.05). A functional linkage between
      potent induction of the major CYP (1-3) genes and transcriptional down-regulation
      of MDR1 gene in drug-resistant tumor cells is hereby hypothesized. Steroid and
      xenobiotic nuclear receptor (SXR) is proposed to mediate the cross-talk between
      the two genes and to recruit potent CYP gene inducers as co-repressor ligands in
      effecting its transcriptional down-regulation of MDR1 gene. Implications for the
      multidrug resistance phenomenon are discussed.

PMID- 17011725
TI  - The process of spermatogenesis liberates significant heat and the scrotum has a
      role in body thermoregulation.
AB  - The temperature in human testis is 2-3 degrees C less than that of body providing
      a suitable environment for sperm production. Pampiniform plexus play a major role
      in this. Authors question the full function of Pampiniform plexus; if it is
      sufficiently efficient to maintain the optimal temperature, why testes are not
      retained in abdomen. The present hypothesis states that during the process of
      spermatogenesis a large amount of heat is liberated as a bye product of energy
      utilization. Testes are purposefully kept away in the dangling scrotum to exclude
      the damage otherwise it would have caused to visceral organs from the heat it
      produced. The heat from testes is carefully liberated by scrotum. The thin skin
      with no subcutaneous fat, scanty hair distribution and presence of more sweat
      glands on it permits easy escape of heat. On exposure to cold, the scrotal
      surface area is minimized by rugosities for heat conservation and cremaster
      muscles lift testes closer to abdomen to provide heat to body.

PMID- 17011726
TI  - Does phenytoin play any role in prevention of Alzheimer's disease?

PMID- 17011727
TI  - Liposuction and diabetes type 2 development risk reduction in the obese patient.
AB  - Obesity is a disabling disease which has gained greater attention worldwide and
      particularly in the United States. It significantly increases the risk for other
      diseases such as insulin independent diabetes mellitus also known as diabetes
      type 2. The most common surgical procedure for obesity is liposuction. It is
      traditionally performed either as small-volume liposuction or large-volume
      liposuction, the majority being small-volume liposuction procedures. Large-volume
      and small-volume liposuction have been clinically shown to improve insulin
      sensitivity in obese patients thus reducing their risk of developing type 2
      diabetes. In this paper, evidence is presented to support the hypothesis that
      liposuction disrupts the pathway that brings about insulin insensitivity in the
      obese patient. It is proposed that using liposuction in the overall treatment of
      obesity could lead to an improvement in insulin sensitivity and thus greatly
      improve the quality of life of the obese patient.

PMID- 17011728
TI  - Revisiting the methylation hypothesis for the psychoses.

PMID- 17011729
TI  - Cave smoke: air pollution poisoning involved in Neanderthal extinction?

PMID- 17011730
TI  - Drosophila RhoGEF4 encodes a novel RhoA-specific guanine exchange factor that is
      highly expressed in the embryonic central nervous system.
AB  - Rho family small GTPases act as molecular switches that regulate neuronal
      morphogenesis, including axon growth and guidance, dendritic spine formation, and
      synapse formation. These proteins are positively regulated by guanine nucleotide
      exchange factors (GEFs) of the Dbl family. This study describes the
      identification and characterization of Drosophila RhoGEF4 (DRhoGEF4), a novel Dbl
      family protein that is specifically expressed in the central nervous system
      during Drosophila embryogenesis. The predicted amino acid sequence of DRhoGEF4
      contains a Dbl homology (DH) domain and an adjacent C-terminal pleckstrin
      homology (PH) domain, which are most closely related to those of mammalian
      frabins. In this study, the DH-PH motif is shown to enhance the dissociation of
      GDP from either RhoA or Rac1 but not from Cdc42 in vitro. In addition, p21
      binding domain pull-down assays demonstrate that DRhoGEF4 activates RhoA, but
      neither Rac1 nor Cdc42 in HEK293 cells. Finally, overexpression of DRhoGEF4 is
      able to induce assembly of stress fibers in cultured NIH3T3 cells. Taken
      together, these findings suggest that DRhoGEF4 may participate in cytoskeleton
      related cellular events by specifically activating RhoA in neuronal
      morphogenesis.

PMID- 17011731
TI  - The DcMaster Transposon Display maps polymorphic insertion sites in the carrot
      (Daucus carota L.) genome.
AB  - DcMaster is a family of PIF/Harbinger-like class II transposable elements
      identified in carrot. We present a modified Transposon Display molecular marker
      system allowing amplification of genomic regions containing DcMaster elements. We
      scored 77 DcMaster Transposon Display (DcMTD) amplicons, of which 54 (70%) were
      segregating in the F(2) progeny from the cross between wild and cultivated
      carrot. Segregating amplicons were incorporated into a previously developed
      molecular linkage map of carrot. Twenty-eight markers were attributed to the wild
      parent, 23 originated from the cultivated parent, and three markers remained
      unlinked. The markers were evenly distributed among the nine linkage groups.
      However, differences in the distribution pattern of DcMaster insertion sites in
      the genomes of the wild and cultivated parent were observed. Specificity of the
      obtained amplicons was confirmed by sequencing and three putative DcMaster
      subfamilies, differing in the sequence of their terminal inverted repeats, were
      revealed.

PMID- 17011732
TI  - Rapid sex chromosomal chimerism analysis in heterosexual twin female calves by
      Loop-mediated Isothermal Amplification.
AB  - We attempted to apply an embryo sexing kit with Loop-mediated Isothermal
      Amplification (LAMP) to sex chromosomal chimerism analysis in heterosexual twin
      female calves. Peripheral blood was used for the amplification of male-specific
      DNA, derived from XY leukocytes. When blood samples were diluted 1:1000 in LAMP
      reaction mixture, hemoglobin or blood coagulation did not influence the turbidity
      measurement of the reaction mixture for detection of amplified DNA. This
      procedure detected the existence of XY leukocytes of 0.01% in female blood.
      Furthermore, all heterosexual twin female calves, bearing sex chromosomal
      chimerism based on karyotyping and PCR, showed male-specific DNA from peripheral
      blood by LAMP. These results indicated that the embryo sexing kit with LAMP was
      available for sensitive detection of sex chromosomal chimerism. This procedure
      made it possible to detect easily Y-chromosome specific DNA in a short interval
      compared with PCR, and was convenient for field application of freemartin
      diagnosis.

PMID- 17011733
TI  - Screening for anti-infective properties of several medicinal plants of the
      Mauritians flora.
AB  - Several plants of the Mauritian flora alleged to possess anti-infective
      properties were studied against different strains of pathogenic bacteria and
      fungi. The grounded dried plant materials were extracted with different
      extractants and screened for anti-microbial activity using the disk diffusion and
      the micro-dilution techniques. Preliminary screening revealed that the methanol
      extracts were most active. Salmonella enteritidis, Enterobacter cloacae and
      Bacillus subtilis were the three test organisms, which were found to be
      susceptible to all the crude methanolic extracts of the different plants
      investigated (100% susceptibility), followed by Escherichia coli (57.1%) and
      Pseudomonas aeruginosa (57.1%), and Staphylococcus aureus (28.6%). The lowest
      minimum inhibitory concentration recorded for the different crude methanol
      extracts against Staphylococcus aureus, Escherichia coli, Salmonella enteritidis,
      Enterobacter cloacae, Bacillus subtilis and the mould fungus Candida albicans
      were 500, 1000, 125, 250, 1000 and 125 micro g/ml, respectively. Bioautography
      using Cladosporium cucumerinum revealed that dichloromethane (DCM) extracts had
      the highest activity against the phytopathogenic fungus. It was also noted that
      the DCM extracts of Michelia champaca and Antidesma madagascariense yielded the
      maximum number of growth inhibiting compounds against Cladosporium cucumerinum.
      Activity of the different crude extracts was also investigated against several
      phytopathogenic filamentous fungi, Colletotrichum glocosporoides, Rhizoctonia
      solani, Sclerotinia sclerotium, Guignardia sp. and Fusarium oxysporum. It was
      found that crude hexane extracts as well as crude DCM extracts exhibited marked
      activity against several strains of fungi, especially Colletotrichum
      glocosporoides, Sclerotinia sclerotium and Guignardia sp.

PMID- 17011734
TI  - Primary nasolacrymal tuberculosis diagnosed after dacryocytorhinostomy.
AB  - Although tuberculosis (TB) is common and well recognized in many countries,
      unusual presentations of the disease sometimes raise difficulties in differential
      diagnosis. Primary tuberculosis of the lacrimal sac and the nasolacrimal duct is
      an extremely rare presentation of extra-pulmonary tuberculosis.
      Dacryocystorhinostomy alone is not sufficient for the treatment of these patients
      and an anti-tuberculous therapy has to be added. Here we present a patient with
      primary tuberculosis, which is limited to the inferior meatus and filled the
      entire lacrimal sac on the left side. The patient underwent endoscopic
      dacryocystorhinostomy due to obstruction of the nasolacrimal duct and culture of
      the granulation tissue, taken from the lacrimal sac revealed mycobacterial
      tuberculosis. The patient was improved with anti-tuberculous therapy that was
      added to the surgery. Primary tuberculosis is a rare granulomatous disease of the
      nasolacrimal system, which should be considered in the differential diagnosis to
      plan the effective treatment.

PMID- 17011735
TI  - [Long term outcomes in HIV infected adolescents followed from birth].

PMID- 17011736
TI  - Determination of oridonin in rat plasma by reverse-phase high-performance liquid
      chromatography.
AB  - A method for quantitative determination of oridonin in rat plasma using reversed
      phase high-performance liquid chromatography (RP-HPLC) coupled with UV
      spectrometry was established and the method was applied to a pharmacokinetics
      study of oridonin in rats. From a variety of compounds and solvents tested,
      ticolpidine was selected as the internal standard (IS) and ethyl acetate was
      found to be the best solvent for extracting oridonin from plasma samples. RP-HPLC
      analysis of the extracts was performed on an analytical column (DIKMA ODS, 200 mm
      x 4.6 mm; i.d., 5 microm) equipped with a security guard pre-column system. There
      was a good linearity over the range 0.05-8.0 microg/mL (r>0.99). The recoveries
      were about 95.0% in plasma, and the intra- and inter-day coefficients of
      variation were less than 9.0% in all cases. The limit of detection (LOD) was
      0.025 microg/mL and the lower limit of quantification (LLOQ) was 0.05 microg/mL.
      The RP-HPLC method was readily applied to quantitate oridonin in rat plasma
      within 24 h in a pharmacokinetics study where experimental rats received a single
      dose of oridonin (12.5 mg/kg) and the result was presented.

PMID- 17011737
TI  - Effects of a national medication education program in Taiwan to change the
      public's perceptions of the roles and functions of pharmacists.
AB  - OBJECTIVE: To evaluate the effect of a national medication education program on
      public's perceptions of the roles and functions of pharmacists in Taiwan.
      METHODS: This was a single group, pre- and post-comparison study. The subjects
      were 955 community residents enrolled in the Community Education Program on
      Medication Use (CEPMU) between September 2003 and January 2004 in Taiwan. The
      program was a pharmacist-facilitated national education program implemented at 31
      community universities nationwide. The education program consisted of 14 lectures
      that were delivered over a 4-month period. A questionnaire was administered
      before and after the program to survey the subjects on their usual drug
      information sources, their evaluation of the credibility of the drug-information
      sources, and their perceptions of the roles and functions of pharmacists in
      Taiwan. Paired t-test was used to analyze the difference between pre- and post
      tests with a significant level set at 0.05 a priori. RESULTS: At the end of the
      program, the subjects were more likely to request drug information from
      healthcare professionals as compared to the baseline (p < 0.05). They also had
      more confidence in the information provided by the community pharmacists (p <
      0.05) and had a better understanding of the roles and functions of pharmacists (p
      < 0.05). CONCLUSIONS: The national medication education program facilitated by
      pharmacists helps to direct the subjects to pharmacists or other healthcare
      givers for drug information. It also improves their perceptions of the roles and
      functions of pharmacists in Taiwan. PRACTICE IMPLICATIONS: Pharmacists' proactive
      participation in health education helped society to appreciate the roles and
      functions of pharmacists as knowledge workers in terms of drug information
      providers and safeguards of drug use.

PMID- 17011739
TI  - [Drug-eluting stent, intraventricular haemorrhage, ventricular drainage,
      favourable outcome].

PMID- 17011738
TI  - Effect of gender and visit length on participation in pediatric visits.
AB  - OBJECTIVE: To examine the effect of child, physician and parent genders as well
      as visit length on participation. METHODS: We analyzed videotapes and
      sociodemographics from 100 pediatric visits. Using the Roter Interaction Analysis
      System, coded utterances were aggregated to reflect key visit tasks: information
      giving, information gathering and relationship building. Negative binomial models
      were used to analyze how participation was associated with participants' genders
      and visit length. RESULTS: After adjustment, girls did twice as much relationship
      building as boys (incidence rate ratio = 2.33, 95% confidence interval = 1.01
      5.36) and their physicians did 34% more information gathering (1.34, 1.16-1.55).
      Female physicians did 29% less information giving (0.71, 0.54-0.94). Having the
      father accompany the child reduced child relationship building 76% (0.24, 0.08
      0.69) and reduced physician information giving 14% (0.86, 0.75-0.995), compared
      to having mother accompany. After adjusting for participants' genders, longer
      visits were associated with more participation for all participants. CONCLUSION:
      Child participation was impacted by child gender and by the accompanying parent's
      gender as well as the visit length. PRACTICE IMPLICATIONS: Because gender-based
      patterns of participation are evident in childhood, interventions to facilitate
      participation might begin early in life. To improve participation, interventions
      might include advocating for policies to support longer visit lengths.

PMID- 17011740
TI  - Influence of oil droplet surface charge on the performance of antibody--emulsion
      conjugates.
AB  - Targeted drug delivery requires binding of (and subsequent uptake by) the carrier
      to target cells. The purpose of our present study is to compare the binding and
      uptake of emulsions with different electric surface properties to SK-BR3 cell
      line, which over-expresses the HER2 receptor. Cationic emulsion was prepared by
      incorporating 0.25% w/w of the cationic lipid, stearylamine in the formulation
      while the anionic emulsion formulation was identical but lacking stearylamine.
      Immunoemulsions were prepared by conjugating the 2-iminothiolane derivative of
      the monoclonal antibody trastuzumab (Herceptin) through the reactive maleimide
      group of the octadecyl-4-(maleimidomethyl)cyclohexane-carboxylic amide linker
      which was incorporated in the oil phase of the anionic and cationic emulsions.
      Cationic emulsion exhibited a droplet size of approximately 130 nm and a zeta
      potential of +50 mV compared to anionic emulsion with a droplet size of
      approximately 140 nm and a zeta potential of -30 mV which decreased to -5 mV
      following antibody coupling. There was no significant difference in the coupling
      efficiency of trastuzumab to anionic and cationic emulsions which was in the
      range of 60-70%. The cationic emulsion and immunoemulsion appeared to be
      physically stable over a long period of time, as indicated by particle-size
      measurements while the droplets of the anionic immunoemulsion coalesced with time
      resulting in phase separation within 20 days storage at 4 degrees C. The results
      of binding and uptake to cells showed that both cationic and anionic
      immunoemulsions bind and internalized to cells much more than the respective
      blank emulsions. The enhanced penetration of the probe coumarin-6 with both
      immunoemulsions clearly indicated that the internalization process was mainly
      controlled by a cell-receptor endocytosis mechanism mediated by the binding
      affinity of trastuzumab to the cell surface receptor since the uptake of the
      cationic immunoemulsion was not significantly different from the uptake of the
      anionic immunoemulsion. However, only the cationic immunoemulsion might be
      considered for further investigation in view of its long standing physical
      stability.

PMID- 17011741
TI  - Induction of CYP2B and CYP2E1 in precision-cut rat liver slices cultured in
      defined medium.
AB  - Many drugs and endogenous substances undergo biotransformation by cytochrome
      P450s (CYPs), and some drugs are also capable of modulating the expression of
      various CYPs. Knowledge of the potential of a drug to modulate CYPs is useful to
      help predict potential drug interactions. This study utilized precision-cut rat
      liver slices in dynamic organ culture to assess the effects of various media on
      the viability of rat liver slices and the expression of CYP2B and CYP2E1 when the
      slices are exposed to phenobarbital and isoniazid, which are drugs capable of
      inducing these respective CYPs. Liver slices were maintained in serum
      supplemented Waymouths medium and two different serum-free media, Hepatozyme
      (Life Technologies) and a new defined medium, which is named BPM. While
      Hepatozyme is considered a suitable medium to support primary hepatocyte
      cultures, this product did not maintain viable liver slices, even for 24 h. The
      serum containing and new defined media maintained viable liver slices for up to
      96 h in culture. Phenobarbital (0.5 mM) and isoniazid (0.1 or 0.6 mM) did not
      affect viability in this model. In the absence of phenobarbital or isoniazid,
      liver slices maintained for 96 h in the new BPM medium maintained the respective
      levels of CYP2B and 2E1 protein at 1.8 and 1.9-fold higher than in slices
      maintained in the serum-containing medium. Phenobarbital exposure (0.5 mM) for 96
      h induced CYP2B protein 5.2-fold in the BPM medium and 2.5-fold in the serum
      containing medium. Isoniazid exposure (0.1 and 0.5 mM) for 96 h induced CYP2E1
      protein 1.9 and 2.1-fold (respectively) in the BPM medium and 2.1 and 2.0-fold in
      the serum-containing medium. The respective CYP enzymatic activities were also
      increased by these drugs in a similar manner. Thus, the new defined BPM medium
      provides suitable conditions for maintaining CYP2B and 2E1 in liver slices and
      supports the investigation of drug-induced modulation of these enzymes.

PMID- 17011742
TI  - Assessing the effects of three dental impression materials on the isolated
      sciatic nerve of rat and frog.
AB  - The effects on nerve tissue of three dental impression pastes were compared in
      this study. Two of the impression pastes, Examix and Express 3M, contained vinyl
      polysiloxane while the other, Xanthopren, did not. An in vitro model based on the
      isolated sciatic nerve of the frog and rat was used. As an indication of the
      proper functioning of the fibres in the nerve, the amplitude of evoked compound
      action potential (CAP) was monitored continuously. The results clearly showed
      that the number of active nerve fibres in the isolated sciatic nerves of either
      rat or frog exposed directly to impression pastes containing vinyl polysiloxane,
      decreased much faster than those of the nerves in contact to impression material
      without vinyl polysiloxane. When the nerve of the frog was exposed to Xanthopren
      there was a decrease in the CAP to 50% of the control values within 56.87+/-2.42
      h (n=6). This value was called inhibition time to 50%, IT(50) and for Examix it
      was found to be 9.97+/-1.53 h. When the nerve of the rat was exposed to
      Xanthopren, the IT(50) was 15.34+/-2.97 h (n=6) for the Xanthopren and only
      2.86+/-1.20 h for Examix and 2.76+/-0.48 h for Express 3M (n=6). There was no
      significant difference between the action of the last two compounds (P=0.85).
      This fast nerve fibre inactivation could be caused either by the chemical used
      for the synthesis of the two impression pastes, Examix and Express 3M, or by the
      unusual constriction of the nerve when it is embedded in the materials with vinyl
      polysiloxane. There is strong evidence to support the first case, since the
      incubation of the nerve in the presence of Examix, Express 3M and Xantopren in a
      way so the nerve was not in contact with the impression pastes, shows a much
      faster decrease of the CAP in the presence of the first two pastes. The decrease
      is caused by the death of nerve fibres, since there is no recovery in the CAP
      after the removal of Examix from the incubating saline.

PMID- 17011743
TI  - Using verbal fluency to detect very mild dementia of the Alzheimer type.
AB  - The study sample included 76 healthy older adults and 77 individuals with very
      mild dementia of the Alzheimer type (DAT). Semantic (animal) and letter (S and P)
      fluency tasks were used to examine quantitative (word generation) and qualitative
      (category clustering and switching) aspects of verbal fluency. The goal of the
      study was to evaluate the utility of fluency tasks in discriminating between
      healthy aging and very mild DAT. Our results indicated better performance for the
      healthy group than the DAT group in terms of number of words, number of clusters,
      number of switches, and size of clusters generated (an exception was clustering
      on letter S fluency). Clustering and switching variables were significantly
      correlated with number of words generated and therefore were not included in
      discriminant analysis. Discriminant analysis revealed that the combination of
      semantic fluency and narrative recall may be particularly useful in
      differentiating healthy aging from very mild DAT.

PMID- 17011745
TI  - Stress primes microglia to the presence of systemic inflammation: implications
      for environmental influences on the brain.

PMID- 17011744
TI  - Efficacy of clone fingerprinting methodologies.
AB  - With the development of new high-information content fingerprinting techniques
      for constructing BAC-based physical maps, physical map construction is
      accelerating and it is important to determine which methodologies work best. In a
      recent publication (Z. Xu et al., 2004, Genomics 84:941-951), Xu et al. evaluated
      five different techniques (one agarose-based and four using multiple enzymes) and
      concluded that a two-enzyme technique was superior. In addition, they found that
      no benefit was gained from fingerprinting more than 10x coverage. In this paper
      we report our own extensive simulation results, which lead to contrasting
      conclusions. Our data indicate that the five-enzyme method known as SNaPshot is
      the most effective and that the assembly can in fact be significantly improved
      with greater than 10x coverage.

PMID- 17011746
TI  - Effects of ERalpha overexpression on female reproduction in mice.
AB  - Recently, we generated transgenic mice in which ERalpha can be inducibly
      overexpressed in reproductive tissues (ERalpha overexpressors). These mice were
      used to test the hypothesis that prenatal and postnatal ERalpha overexpression
      reduces female fertility. To do so, litter sizes, ovulation, follicle numbers,
      uterine histology, implantation sites, and hormone levels were compared in
      ERalpha overexpressors and controls. The data indicate that ERalpha
      overexpressors have reduced fertility compared to controls and that the reduced
      fertility is not due to reduced ovulatory capacity, altered levels of estradiol,
      FSH, and LH, or impaired follicular growth. ERalpha overexpressors, however, had
      a higher number of apoptotic cells in the endometrial epithelium and a reduced
      number of implantation sites compared to controls. Thus, the increased number of
      apoptotic cells and reduced number of implantation sites observed in ERalpha
      overexpressing uteri compared to controls may, in part, account for the reduced
      litter size produced by ERalpha overexpressing females.

PMID- 17011747
TI  - Analysis of gene expression profiles in the offspring of rats following maternal
      exposure to xenoestrogens.
AB  - Many environmental chemicals are known endocrine disruptors (EDs). These have the
      potential to alter endocrine systems via various mechanisms that include binding
      to hormone receptors, thereby either mimicking or blocking the hormone actions
      and causing abnormal gene expression. Here, to elucidate the molecular
      mechanism(s) underlying the detrimental effects associated with the estrogenicity
      of these chemicals, we determined whether gene profiles were altered in rats
      exposed to 4-tert-octyphenol (OP) and diethylstilbestrol (DES) in utero. Pregnant
      rats were treated with a high dose of OP (600 mg/kg BW per day) or DES (500
      microg/kg BW per day) at gestational days (GD) 17, 18 and 19. Both dams and
      neonates were euthanized at lactation day (LD) 5. The transcript profiles of
      uterine tissue were compared in treated versus control in both maternal and
      neonatal sites using cDNA microarray to determine the expression levels of
      approximately 13,000 genes and expressed sequence tags (ESTs). The expression
      levels of some known estrogen-responsive genes, i.e., complement component 3,
      epidermal growth factor receptor or c-fos oncogene and calbindin 3, as well as
      some other randomly selected genes, including general transcription factor IIa,
      transcription factor 4 and lymphocyte specific 1, were increased by OP and/or DES
      treatment in the uteri of both maternal and neonate groups. However, the
      magnitude of these alterations in gene expression differed markedly between dams
      and neonates, most likely reflecting the temporal susceptibility of the
      reproductive tract to estrogenic chemicals. Importantly, the altered gene
      patterns identified by microarray analysis were confirmed by RT-PCR and real-time
      RT-PCR. Fifteen primers were designed to amplify specific altered genes. These
      genes were selected for validation because of their markedly increased expression
      levels and they were classified on the basis of gene ontology. Overall, a high
      correlation was observed between microarray and real-time PCR data. Taken
      together, these results indicate that placental exposure to OP or DES may cause
      temporal changes in gene expression in the uteri of dams and neonates. Moreover,
      these findings may provide useful indicators of the adverse effects of EDs and
      prove particularly important in elucidating the effects of xenoestrogens on
      estrogen-responsive tissues, such as the developing reproductive tract.

PMID- 17011748
TI  - Comparison of five commercial DNA extraction kits for the recovery of Francisella
      tularensis DNA from spiked soil samples.
AB  - Francisella tularensis is the etiologic agent of the zoonotic disease tularemia
      and is thought to be maintained in the environment principally by various
      terrestrial and aquatic vertebrate animals. The organism is known to persist in
      water or mud for long periods of time and Francisella-specific DNA has been
      identified from water and soil. To gain a better understanding of the ecology and
      epidemiology of F. tularensis, it will be important to further explore its
      distribution in the environment. Therefore, methods must be established to
      efficiently extract Francisella-specific DNA from the soil and be able to
      eliminate potential PCR inhibitors. Thus, we evaluated five commercial DNA
      extraction kits for their ability to recover F. tularensis-specific DNA from soil
      samples and eliminate potential PCR inhibitors. The kits evaluated included the
      Puregene DNA purification kit, QIAamp Stool Mini kit, Epicentre Biotech
      SoilMaster DNA extraction kit, and the UltraClean and PowerMax soil DNA isolation
      kits from MoBio. Soil samples were spiked with gamma-irradiated F. tularensis SHU
      4 strain (corresponding to a range from 10 to 10(5)CFU). Spiked samples were
      extracted with each kit and evaluated using a F. tularensis-specific real-time
      PCR assay and an internal positive control assay that measures the presence of
      potential PCR inhibitors. DNA extraction using the UltraClean and PowerMax kits
      resulted in the most consistently positive results at the lowest limit of
      detection (20 and 100CFU/g soil, respectively) for all soil types tested,
      suggesting that these kits can provide the most sensitive methods for extracting
      F. tularensis from environmental soil samples. Processing time and cost were also
      evaluated.

PMID- 17011749
TI  - Attention in natural scenes: Neurophysiological and computational bases.
AB  - How does attention operate in natural scenes? We show that the receptive fields
      of inferior temporal cortex neurons that implement object representations become
      small and located at the fovea in complex natural scenes. This facilitates the
      readout of information about an object that may be reward or punishment
      associated, and may be the target for action. Top-down biased competition to
      implement attention has a much weaker effect in complex natural scenes than in
      otherwise blank scenes with two objects. Part of the solution to the binding
      problem is thus that competition and the foveal cortical magnification factor
      emphasize what is present at the fovea, and limit the binding problem. Part of
      the solution to the binding problem is that neurons respond to combinations of
      features present in the correct relative spatial positions. Stimulus-dependent
      neuronal synchrony does not appear to be quantitatively important in feature
      binding, and in attention, in natural visual scenes, at least in the inferior
      temporal visual cortex, as shown by information theoretic analyses. The
      perception of multiple objects in a scene is facilitated by the fact that
      inferior temporal visual cortex neurons have asymmetrical receptive fields with
      respect to the fovea in complex scenes. Computational models of this processing
      are described.

PMID- 17011750
TI  - The PI3 kinase-Akt pathway mediates Wnt3a-induced proliferation.
AB  - Wnt3a activates proliferation of fibroblasts cells via activation of both
      extracellular signal-regulated kinase (ERK) and Wnt/beta-catenin signaling
      pathways. In this study, we show that the phosphatidyl inositol 3 kinases (PI3K)
      Akt pathway is also involved in the Wnt3a-induced proliferation. Akt was
      activated within 30 min by Wnt3a in NIH3T3 cells. By Wnt3a treatment, activated
      Akt was transiently accumulated in nucleus although beta-catenin was accumulated
      in the nucleus of cells in a prolonged manner. The Wnt3a-induced Akt activation
      was not affected by siRNA-mediated reduction of beta-catenin, indicating that
      Wnt3a-induced Akt activation may occur independently of beta-catenin. The Wnt3a
      induced Akt activation was abolished by pre-treatment with PI3K inhibitor,
      LY294002 and Wortmanin, but not by MEK inhibitor, U0126, indicating that Wnt3a
      activates Akt via PI3K. The growth and proliferation induced by Wnt3a were
      blocked by treatments of the PI3K inhibitors. Furthermore, Wnt3a-induced
      proliferation was blocked by Akt siRNA. These results reveal that the PI3K-Akt
      pathway mediates the Wnt3a-induced growth and proliferation of NIH3T3 cells.

PMID- 17011751
TI  - Raf-1 and B-Raf promote protein kinase C theta interaction with BAD.
AB  - PKCtheta regulates the proliferation, survival and differentiation of T-cells.
      Here we show that PKCtheta interacts with Raf-1 and B-Raf kinases. Raf-1 enhanced
      the kinase activity of associated PKCtheta, while PKCtheta reduced the catalytic
      activity of associated Raf-1. In contrast, B-Raf binding did not affect PKCtheta
      kinase activity, and PKCtheta did not change B-Raf activity. Coexpression of
      mutationally activated Raf-1 in cells enhanced the phosphorylation of T538 in the
      PKCtheta activation loop. PKCtheta and Raf cooperated in terms of binding to BAD,
      a pro-apoptotic Bcl-2 family protein that is inactivated by phosphorylation.
      While neither Raf-1 nor B-Raf could phosphorylate BAD, they enhanced the ability
      of PKCtheta to interact with BAD and to phosphorylate BAD in vitro and in vivo,
      suggesting a new role for Raf proteins in T-cells by targeting PKCtheta to
      interact with and phosphorylate BAD.

PMID- 17011752
TI  - Repair of palatal defect with nasal septal flap.
AB  - Postoperative oronasal fistula in cleft palate repair is common and usually
      repaired with local flaps or buccal flaps with some benefits. Considering the
      high recurrence rate after surgery, a new method for oronasal repair using septal
      flaps is described.

PMID- 17011753
TI  - Quantitative analysis of the elastic fibres in the human temporomandibular
      articular disc and its attachments.
AB  - A quantitative study of the elastic fibres found in the human temporomandibular
      disc and its attachments was performed. Seven left discs from 57- to 82-year-old
      subjects, without macroscopic evidence of a TMJ disorder, were analysed and
      prepared in parasagittal sections. The surface amount was measured, thresholded
      and expressed from 0 to 1, using microscopic digitized views after Weigert's
      resorcin-fuchsin staining of elastic fibres. Fibre density rates ranged from 0 to
      0.687. The mean density was 0.1532 (sigma=0.1150) in the upper bilaminary zone,
      0.1097 (sigma=0.1159) in the lower bilaminary zone, 0.0474 (sigma=0.0782) in the
      anterior band, 0.0180 (sigma=0.0603) in the posterior band and null in the
      intermediate zone. The difference in density rate between the structures was
      significant, except for the posterior band and the intermediate zone. The elastic
      fibre density rates in central and medial locations of the upper and lower
      bilaminary zones were twice as big as in the lateral locations. In the anterior
      band, the elastic fibre density was less abundant medially than in its lateral
      part. These quantitative results support the current elastic fibre distribution
      scheme, and confirm the necessity of studying their orientation, taking into
      account age and temporomandibular joint health parameters.

PMID- 17011754
TI  - Influence of viral chronic hepatitis co-infection on plasma drug concentrations
      and liver transaminase elevations upon therapy switch in HIV-positive patients.
AB  - It is still controversial whether viral hepatitis co-infection can influence
      antiretroviral plasma drug concentrations and whether drug concentrations are
      correlated with liver enzyme elevations during highly active antiretroviral
      therapy. An analysis of data from a cohort of 220 human immunodeficiency virus
      (HIV)-infected patients was conducted. Univariate and multivariate logistic
      analyses were performed to identify predictors of plasma drug concentrations. The
      association of transaminase elevation with higher plasma drug concentrations was
      explored following stratification of patients into HIV monoinfected and hepatitis
      C virus (HCV) and/or hepatitis B virus (HBV) co-infected groups. Hepatitis co
      infections were independently correlated with drug concentrations above the
      therapeutic cut-offs at Week 1 (P=0.06), Week 4 (P=0.04) and Week 12 (P=0.005).
      The apparent effect was independent of the possible impact exerted by other
      variables such as demographics and medication adherence. The incidence of
      relevant hypertransaminasaemia was low. Patients with hepatitis co-infections had
      higher rates of transaminase elevation than monoinfected HIV patients; however,
      risk of transaminase elevation was not associated with drug concentrations. The
      presence of HCV and/or HBV co-infections correlated with higher plasma drug
      concentrations, although it did not appear to influence hepatotoxicity risk.

PMID- 17011755
TI  - An essential role for zebrafish Fgfrl1 during gill cartilage development.
AB  - The vertebrate craniofacial skeleton develops via a complex process involving
      signaling cascades in all three germ layers. Fibroblast growth factor (FGF)
      signaling is essential for several steps in pharyngeal arch development. In
      zebrafish, Fgf3 and Fgf8 in the mesoderm and hindbrain have an early role to
      pattern the pouch endoderm, influencing craniofacial integrity. Endodermal FGF
      signaling is required for the differentiation and survival of postmigratory
      neural crest cells that form the pharyngeal skeleton. We identify a novel role
      for zebrafish Fgf receptor-like 1a (Fgfrl1a) that is indispensable during gill
      cartilage development. We show that depletion of Fgfrl1a is sufficient to abolish
      cartilage derivatives of the ceratobranchials. Using an Fgfrl1a-deficient model,
      we analyzed expression of genes critical for chondrogenesis in the different
      compartments of the developing pharyngeal arch. Fgfrl1a-depleted animals
      demonstrate typical neural crest specification and migration to populate the arch
      primordia as well as normal pouch segmentation. However, in the absence of
      Fgfrl1a, larvae fail to express the transcription factor glial cells missing 2
      (gcm2), a gene necessary for cartilage and gill filament formation, in the
      ectodermal lining of the branchial arches. In addition, two transcription factors
      essential for chondrogenesis, sox9a and runx2b, fail to express within the
      mesenchymal condensations of the branchial arches. A duplicate zebrafish gene,
      fgfrl1b, has now been identified. We show that Fgfrl1b is also required for
      proper formation of all ventral cartilage elements and acts cooperatively with
      Fgfrl1a during gill cartilage formation.

PMID- 17011756
TI  - Improving membrane activity of oligonucleotides by cetylpyridinium chloride: an
      electrochemical study.
AB  - The interaction of phospholipid membranes and oligonucleotides complexed with a
      positively charged surfactant is reported. Phospholipid membranes were assembled
      at the interface between an immobilized organic phase and an aqueous phase using
      the Langmuir-Blodgett (L-B) technique. The interaction and adsorption of the
      naked oligonucleotides and oligonucleotides complexed with cetylpyridinium
      chloride (CP) was studied electrochemically using cyclic voltammetry (CV) and ac
      voltammetry. Interfacial capacitance, obtained indirectly from ac-voltammetry as
      a function of interfacial potential, was fitted to the theory based on the
      solution of the Poisson-Boltzmann equation. It was shown that both types of naked
      oligonucleotides (phosphoromonothioates and phosphodiesters) adsorb on the lipid
      monolayers poorly. The introduction of CP to the system increases the adsorption
      efficiency significantly. However, one phosphoromonothioate appeared to form a
      compact globule with CP instead of adsorbing to the lipid membrane. These results
      demonstrate that electrochemical methods are a powerful tool for probing the
      behavior of drugs in the vicinity of model cell membranes.

PMID- 17011757
TI  - [Abscess of the buttock and chronic cough in a teenager].

PMID- 17011758
TI  - [Perinatal consequences of maternal connective tissue diseases: a prospective
      study of 73 cases].
AB  - AIM: To describe a group of newborns born from mothers with connective tissue
      diseases, to determine their perinatal characteristics and the neonatal
      morbidity, and to assess the possible role of drugs received by mothers on the
      obstetrical and neonatal morbidity. PATIENTS AND METHODS: During a 34-month
      period, newborns born from mothers with connective tissue diseases and followed
      in a single center were prospectively included in the study. In all cases,
      maternal treatments (i.e. hydroxychloroquine and/or prednisone) were continued
      during pregnancy. RESULTS: Among the 73 included infants, 18 (25%) were born
      before 37 weeks of gestation and 3 (4%) were small for gestational age. A
      neonatal lupus syndrome with facial rash and thrombopenia was observed in 1 case.
      No neonatal congenital heart block was observed and maternal treatment did not
      significantly influence the mean PR or QT intervals. Four infants had minor
      congenital abnormalities and 3 had feto-maternal infection. CONCLUSION: These
      data show that perinatal morbidity is lower than that previously published. We
      postulate that a strict follow-up during pregnancy may have played a significant
      positive role in these results.

PMID- 17011759
TI  - Gene-lifestyle interaction on risk of type 2 diabetes.
AB  - The descriptive epidemiology of type 2 diabetes suggests that gene-lifestyle
      interactions are critical to the development of the condition. However,
      unravelling the molecular detail of these interactions is a complex task. The
      existing literature is based on small intervention studies or cross-sectional
      observational quantitative trait studies. Our systematic review of the literature
      identified some evidence of interactions, most notably for a common variant in
      the PPAR-gamma gene which appears to interact with the nature of dietary fat
      intake. Other interactions have been reported for adrenoceptors, uncoupling
      proteins, fatty acid binding proteins, apolipoproteins and lipoprotein lipase.
      There are, to date, no reports based on the ideal study design which is a case
      control study nested within a cohort. To limit the likelihood of false discovery,
      such studies would need to be large and the search for interaction should be
      restricted to a priori biologically driven hypotheses. Additional study designs
      that examine differential response to lifestyle change or test interaction in the
      context of quantitative trait studies would complement the nested case-control
      approach, but the emphasis here should be on precision of measurement of both
      phenotype and lifestyle behaviour.

PMID- 17011760
TI  - Metabolism of eicosanoids and their action on renal function during ischaemia and
      reperfusion: the effect of alprostadil.
AB  - Eicosanoids, active metabolites of arachidonic acid (AA), play an important role
      in the regulation of renal haemodynamics and glomerular filtration. Our study
      verified the hypothesis on the positive action of exogenously administered PGE(1)
      on renal function during an operation with temporary ischaemia of the lower half
      of the body. Also the effect of alprostadil (prostaglandin E(1) analogue)
      administered during the operation of an abdominal aorta aneurysm on the
      postoperative systemic metabolism of AA and the glomerular filtration rate (GFR)
      was investigated. The study included 42 patients with a diagnosed abdominal aorta
      aneurysm who have been qualified for the operation of implantation of the aortic
      prosthesis. The patients were randomly assigned to two groups: the study group
      (I) receiving alprostadil and the control group (II) without alprostadil. The
      levels of hydroxyeicosatetraenoic acids (15-HETE, 12-HETE, 5-HETE) were
      determined by RP-HPLC and the level of thromboxane B(2) (TxB(2)) was determined
      by ELISA in the plasma of the blood drawn from vena cava superior immediately
      before aortic clamping (A) and 5 min after aortic declamping (B). The
      administration of PGE(1) affects the metabolism of 15-HETE in a manner dependent
      on the baseline value of GFR but does not significantly change the postoperative
      renal function. The metabolism of 15-HETE is affected by the baseline value of
      GFR1 and a longer period of ischaemia is correlated with lower concentrations of
      5-HETE during reperfusion. The results of our studies indicate that TxB(2)
      influences the postoperative function of kidneys.

PMID- 17011761
TI  - Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of
      patients with diabetic retinopathy and age-related macular degeneration.
AB  - Cannabinoid receptors and the endocannabinoids (anandamide (N
      arachidonoylethanolamine--AEA) and 2-arachidonoylglycerol (2-AG)), as well as the
      AEA congener, palmitoylethanolamide (PEA), are involved in ocular physiology. We
      measured endocannabinoid and PEA levels by isotope-dilution liquid chromatography
      mass spectrometric analysis in post-mortem eye tissues of patients with diabetic
      retinopathy (DR) or age-related macular degeneration (AMD). In eyes with DR,
      significantly enhanced levels of AEA were found in the retina ( approximately 1.8
      fold), ciliary body ( approximately 1.5-fold) and, to a lesser extent, cornea (
      approximately 1.3-fold). Surprisingly, 2-AG levels were significantly higher (
      approximately 3-fold) only in the iris, whereas PEA levels only slightly
      increased ( approximately 1.3-fold) in the ciliary body. In eyes with AMD,
      significantly enhanced levels of AEA were found in the choroid ( approximately
      1.3-fold), ciliary body ( approximately 1.4-fold) and cornea ( approximately 1.4
      fold), whereas in the retina only a trend towards an increase ( approximately 1.5
      fold) was observed. The tissue- and disease-selective nature of the changes
      observed suggests that the compounds analyzed here may play different roles in
      the control of eye function under different pathological conditions.

PMID- 17011762
TI  - Effector and potential immunoregulatory roles of mast cells in IgE-associated
      acquired immune responses.
AB  - Mast cells are best known as critical effector cells in anaphylaxis and other
      examples of IgE-associated immediate hypersensitivity reactions. However, mast
      cells also can contribute to the development of the late-phase responses that
      occur in some sensitized subjects hours after initial exposure to specific
      antigen, and can promote many of the features of chronic allergic inflammation,
      including tissue remodeling and functional changes in the affected organs. In
      addition to such effector cell functions in IgE-associated immune responses,
      recent evidence indicates that mast cells can importantly influence the
      sensitization phase of at least some acquired immune responses, and can
      contribute to the pathology of autoimmune disorders and to the expression of
      peripheral tolerance.

PMID- 17011764
TI  - TIM-3 in autoimmunity.
AB  - T cell immunoglobulin and mucin domain (TIM)-3 is a molecule expressed on
      terminally differentiated murine Th1 cells but not on Th2 cells. Identification
      of galectin-9 as a ligand for TIM-3 has now firmly established the TIM-3-galectin
      9 pathway as an important regulator of Th1 immunity and tolerance induction. TIM
      3 is similarly expressed on human Th1 cells and not on Th2 cells, which suggests
      that TIM-3 might also contribute to Th1 regulation in humans. In addition,
      genetic data associate the TIM locus and specific TIM-3 polymorphisms with
      various immune-mediated diseases. Most importantly, recent data suggest a novel
      paradigm in which dysregulation of the TIM-3-galectin-9 pathway could underlie
      chronic autoimmune disease states, such as multiple sclerosis.

PMID- 17011763
TI  - Systemic lupus erythematosus: all roads lead to type I interferons.
AB  - In recent years, the study of systemic lupus erythematosus (SLE) patients has
      revealed a central role for type I interferon (IFN) in disease pathogenesis. IFN
      induces the unabated activation of peripheral dendritic cells, which select and
      activate autoreactive T cells rather than deleting them, thus failing to induce
      peripheral tolerance. IFN also directly affects T cells and B cells. Furthermore,
      immune complexes binding to FcgammaR and Toll-like receptors provide an
      amplification loop for IFN production and B-cell activation in SLE. Polymorphisms
      in genes that control IFN production or its downstream signaling pathway, such as
      IRF5, might be responsible for some of these alterations. This novel information
      is leading to the development of IFN antagonists as a potential therapeutic
      intervention in SLE, thus bringing hope to SLE patients.

PMID- 17011766
TI  - Specificity and effector mechanisms of autoantibodies in congenital heart block.
AB  - Complete congenital atrio-ventricular (AV) heart block develops in 2-5% of
      fetuses of Ro/SSA and La/SSB autoantibody-positive pregnant women. During
      pregnancy, the Ro/SSA and La/SSB antibodies are transported across the placenta
      and affect the fetus. Emerging data suggest that this happens by a two-stage
      process. In the first step, maternal autoantibodies bind fetal cardiomyocytes,
      dysregulate calcium homestasis and induce apoptosis in affected cells. This step
      might clinically correspond to a first-degree heart block, and be reversible.
      La/SSB antibodies can bind apoptotic cardiomyocytes and thus increase Ig
      deposition in the heart. The tissue damage could, as a second step, lead to
      spread of inflammation in genetically pre-disposed fetuses, progressing to
      fibrosis and calcification of the AV-node and subsequent complete congenital
      heart block. Early intrauterine treatment of an incomplete AV-block with
      fluorinated steroids has been shown to prevent progression of the heart block,
      making it clinically important to find specific markers to identify the high-risk
      pregnancies.

PMID- 17011767
TI  - The role of SAP and the SLAM family in autoimmunity.
AB  - The signaling lymphocyte activation molecule (SLAM) family of receptors and their
      associated signaling adaptors play a pivotal role in the regulation of various
      stages of cellular immunity. They regulate lymphocyte-lymphocyte interactions
      involved in both cell-mediated and humoral immune responses. Recent evidence
      indicates that members of this family of receptors and signaling intermediates
      are also involved in autoimmunity. These include strictly correlative studies
      showing increased expression of various family members in immune effectors
      involved in rheumatoid arthritis and in inflammatory bowel disease, as well as
      more direct evidence (from various knockout strains of mice) for their role in
      autoimmune processes such as experimental allergic encephalomyelitis and lupus.
      Additional studies defining naturally occurring polymorphic variations in the
      SLAM family show a direct role in initiating the break in tolerance that is an
      essential step in the progression towards autoimmunity.

PMID- 17011768
TI  - Immune therapies of autoimmune diseases: are we approaching a real cure?
AB  - In developed countries, autoimmune diseases represent the third major cause of
      morbidity and mortality after cancer and atherosclerosis and their incidence has
      steadily increased over the past three decades. Conventional therapeutic
      approaches are essentially palliative, anti-inflammatory or immunosuppressive; in
      addition, they are non-specific, unrelated to the antigens involved in disease
      pathogenesis. This explains the growing attention to modern technologies that
      made new biological agents and methods available. A few of these are already
      approved for regular clinical practice; others are still in clinical development
      but hold great promise. The question is: will these new tools allow us to develop
      a real cure for autoimmunity, restoring self-tolerance to target autoantigens?
      This goal is ambitious, namely harnessing the pathogenic immune response while
      preserving the host response to exogenous or unrelated antigens.

PMID- 17011769
TI  - Natural history and therapeutic implications of patients with catamenial
      hemoptysis.
AB  - Evidence as to whether clinician has to give specific treatment in all patients
      of catamenial hemoptysis is unclear. We considered that the current treatment
      such as long-term usage of hormonal agent or surgery might be excessive for the
      catamenial hemoptysis. Therefore, we developed prospective observation study with
      observation strategy and follow-up for the patients. In sequential four patients
      of catamenial hemoptysis between December 2000 and November 2001, physical
      examination, chest X-ray, pelvic ultrasonogram and chest CT scan were taken at
      both the diagnosis and last follow-up. All patients were only observed without
      specific treatment within the limit of the possibility and followed for average
      58 months. Mean age of patients was 23.5years (range, 22-25years). All patients
      have a history of undertaking one or two dilatations and curettages before
      diagnosis. The chest CT scans of all patients presented with ground-glass
      opacities of peripheral location that were disappeared without any residual
      lesion at last follow-up. Hemoptysis of two patients was spontaneously
      disappeared after 6 months. In the other two patients, it was greatly lessened in
      amount and frequency, then clinically insignificant in one. It was disappeared
      after subsequent 2 months and then relapsed two times in the late of follow-up of
      another patient. This study suggests that observation only may be an alternative
      option in the treatment of catamenial hemoptysis.

PMID- 17011770
TI  - Idiopathic pulmonary arterial hypertension in Dutch Caucasian patients is not
      associated with human herpes virus-8 infection.
AB  - Samples of lung tissue, taken at time of lung transplant, from 13 Dutch Caucasian
      patients with idiopathic pulmonary arterial hypertension (iPAH) and 14 patients
      with non-idiopathic PAH were studied for the presence of human herpes virus-8
      (HHV-8). By immunohistochemical staining, in none of patients expression of HHV-8
      latency-associated nuclear antigen 1 (LANA-1) was demonstrated. Using two nested
      polymerase chain reactions (PCR) to amplify part of the open reading frame (ORF)
      65 and ORF 73, we failed to detect HHV-8 DNA in all samples studied. These
      results argue strongly against a role for HHV-8 in the pathogenesis of iPAH.

PMID- 17011771
TI  - A review of municipal solid waste composition in the United Kingdom.
AB  - The move from landfill-based to resource-based waste management systems requires
      a greater knowledge of the composition of municipal solid waste. This paper draws
      together the findings of municipal solid waste (MSW) compositional surveys
      undertaken in the United Kingdom. The results from recent surveys show a good
      agreement over the composition of household-collected waste, but less agreement
      over civic amenity site waste composition. There is insufficient data to allow
      comparisons of the commercial waste element of municipal waste or of the other
      components, and further work is necessary to produce more reliable estimates of
      the composition of these streams. The use of questionnaire surveys and analysis
      of the results suggests that the size and age profile of a household influence
      the generation of household-collected waste. Some research suggests that the
      waste container provided by the local authority and the socio-economic
      classification of a household also influence household-collected waste
      generation, but other studies failed to find this link. Further research is
      required to investigate this by surveying all of the waste disposal routes
      available to specific households.

PMID- 17011772
TI  - Fungicidal value of wood tar from pyrolysis of treated wood.
AB  - The objective of the paper was to estimate the fungicidal value of wood tar
      extracted as a product of pyrolysis of wood previously treated with either
      creosote oil or CCB-type salt preservative. The effectiveness of wood treated
      with one of these two wood tar residuals was compared to the effectiveness of
      wood treated with virgin creosote oil (type WEI-B) and an untreated control. Wood
      was impregnated with alcohol solutions of the two extracted preservatives or
      virgin creosote oil and then subjected to the Coniophora puteana, Poria placenta
      and Coriolus versicolor fungi. The fungicidal values of the investigated
      preservatives were determined with the use of the short agar-block method and the
      aging test according to the standard EN 84. It was found that wood tar extracted
      by pyrolysis of old creosote-treated wood and then used to treat wood may have
      potential as a preservative for wood protection or as a component of
      preservatives.

PMID- 17011773
TI  - Investigation of the nature of MIP recognition: the development and
      characterisation of a MIP for Ibuprofen.
AB  - This paper describes the rational design, generation and testing of a molecularly
      imprinted polymer specific for Ibuprofen. Ibuprofen is a member of the class of
      drugs termed non-steroidal anti-inflammatory drugs (NSAIDS). In the present
      study, Ibuprofen was used as a template molecule for the preparation of
      molecularly imprinted polymers. A MIP has been produced which is capable of
      recognising Ibuprofen in aqueous media. Furthermore, Ibuprofen can be selectively
      extracted from aqueous conditions by molecularly imprinted solid phase extraction
      (MISPE). Recoveries were typically high (>80%) and good selectivity for Ibuprofen
      over structurally related analogues was seen. Moreover, the nature of the
      recognition between MIP and template has been investigated by NMR and molecular
      modelling to analyse whether or not it is possible to predict how well a given
      MIP will perform under set conditions. In addition, the physical characteristics
      of the MIP have been investigated including the particle size distribution on
      exposure of the MIP to different solvents. This has been related to the ability
      of the MIP to rebind Ibuprofen under the same conditions. The data from the
      characterisation of the MIP has been used to further enhance the understanding of
      the nature of MIP recognition.

PMID- 17011774
TI  - Specificity on a knife-edge: the alphabeta T cell receptor.
AB  - The interaction between the alphabeta T cell receptor (TCR) and the peptide bound
      to the major histocompatibility complex class I molecule (pMHC-I) constitutes a
      central interaction in adaptive immunity. How these receptors interact with such
      low affinity while maintaining exquisite specificity for peptide antigen and host
      MHC (MHC-I restriction) remains a challenge to be explained by structural
      immunologists. Moreover, how this extracellular interaction is transmitted as an
      intracellular signal via the CD3 complex remains unresolved. Nevertheless,
      several structures of TCRs, non-liganded and ligated to a defined pMHC-I,
      combined with detailed biophysical analyses, have provided insight of the
      structural basis of MHC-I restriction. In addition, structures of isolated CD3
      components have enabled T cell signalling mechanisms to be postulated. Recent
      findings in this area, which include seven distinct TCR/pMHC-I complexes, have
      fundamental implications in adaptive immunity as well as therapeutic applications
      to modulate the adaptive immune response.

PMID- 17011775
TI  - Translation and validation of the SF-36 Health Survey for use among Turkish and
      Moroccan ethnic minority cancer patients in The Netherlands.
AB  - In this study, the SF-36 Health Survey was translated into two oral Moroccan
      languages and the existing Turkish version was culturally adapted for use in The
      Netherlands, and was tested among 79 Moroccan and 90 Turkish cancer patients.
      There were normal levels of missing item responses but a higher administration
      time. With minor exceptions, the scale structure of the SF-36 was confirmed and
      the reliability of the scales met the 0.70 criterion for group comparisons. The
      questionnaire distinguished clearly between subgroups formed on the basis of
      performance status and was responsive to change in performance status over time.
      Some evidence of differential item function (DIF) was found in both ethnic
      groups. These results support the use of the SF-36 among Turkish and Moroccan
      cancer patients in The Netherlands. Additional studies are needed to confirm the
      psychometrics of the questionnaire when used among these ethnic minority groups
      in other Western European countries.

PMID- 17011776
TI  - Detoxification of sugarcane bagasse hydrolysate improves ethanol production by
      Candida shehatae NCIM 3501.
AB  - Sugarcane bagasse hydrolysis with 2.5% (v/v) HCl yielded 30.29g/L total reducing
      sugars along with various fermentation inhibitors such as furans, phenolics and
      acetic acid. The acid hydrolysate when treated with anion exchange resin brought
      about maximum reduction in furans (63.4%) and total phenolics (75.8%). Treatment
      of hydrolysate with activated charcoal caused 38.7% and 57.5% reduction in furans
      and total phenolics, respectively. Laccase reduced total phenolics (77.5%)
      without affecting furans and acetic acid content in the hydrolysate. Fermentation
      of these hydrolysates with Candida shehatae NCIM 3501 showed maximum ethanol
      yield (0.48g/g) from ion exchange treated hydrolysate, followed by activated
      charcoal (0.42g/g), laccase (0.37g/g), overliming (0.30g/g) and neutralized
      hydrolysate (0.22g/g).

PMID- 17011777
TI  - Heterotrophic bacterial production on solid fish waste: TAN and nitrate as
      nitrogen source under practical RAS conditions.
AB  - The drumfilter effluent from a recirculation aquaculture system (RAS) can be used
      as substrate for heterotrophic bacteria production. This biomass can be re-used
      as aquatic feed. RAS effluents are rich in nitrate and low in total ammonia
      nitrogen (TAN). This might result in 20% lower bacteria yields, because nitrate
      conversion into bacteria is less energy efficient than TAN conversion. In this
      study the influence of TAN concentrations (1, 12, 98, 193, 257mgTAN/l) and stable
      nitrate-N concentrations (174+/-29mg/l) on bacteria yields and nitrogen
      conversions was investigated in a RAS under practical conditions. The effluent
      slurry was supplemented with 1.7gC/l sodium acetate, due to carbon deficiency,
      and was converted continuously in a suspended bacteria growth reactor (hydraulic
      retention time 6h). TAN utilization did not result in significantly different
      observed yields than nitrate (0.24-0.32gVSS/gC, p=0.763). However, TAN was
      preferred compared to nitrate and was converted to nearly 100%, independently of
      TAN concentrations. TAN and nitrate conversions rates were differing
      significantly for increasing TAN levels (p<0.000 and p=0.012), and were
      negatively correlated. It seems, therefore, equally possible to supply the
      nitrogenous substrate for bacteria conversion as nitrate and not as TAN. The
      bacteria reactor can, as a result, be integrated into an existing RAS as end of
      pipe treatment.

PMID- 17011778
TI  - Optimization of nutritional requirements and feeding strategies for clavulanic
      acid production by Streptomyces clavuligerus.
AB  - The present work reports the nutritional requirements and environmental
      conditions for submerged culture of Streptomyces clavuligerus for clavulanic acid
      production using orthogonal matrix method (Taguchi L(16) design) and also fed
      batch fermentation for clavulanic acid production by feeding glycerol, arginine
      and threonoine to the fermentation medium intermittently. Clavulanic acid
      production was increased by 18% with the span of feeding glycerol and reached a
      maximum at 1.30mg/ml with 120h glycerol feeding as compared to 1.10mg/ml in the
      control. The production also increased with the span of feeding amino acids and
      reached a maximum of 1.31 and 1.86mg/ml with feeding arginine and threonine,
      respectively in 120h. There was an overall increase of 18% and 9% in clavulanic
      acid production with arginine and threonine feeding as compared to the respective
      controls (1.10 and 1.70mg/ml, respectively).

PMID- 17011779
TI  - Facile synthesis of substituted thiophenes via Pd/C-mediated sonogashira coupling
      in water.
AB  - The first successful Pd/C-mediated Sonogashira coupling of iodothiophene with
      terminal alkynes in water is described here. Pd/C-CuI-PPh(3) was found to be an
      efficient catalyst system for this coupling reaction. Using this economic and
      reliable process a variety of acetylenic thiophenes with a wide range of
      functional groups were prepared in good yields. Synthetic applications and in
      vitro anticancer properties of some of the compounds synthesized are described.

PMID- 17011780
TI  - Does sedation practice delay time to extubation?
AB  - Criteria for performing a spontaneous breathing trial (SBT) have not been
      evaluated in controlled trials. An important component of these criteria is
      neurological status. The objective of this study was to evaluate whether
      physicians take mental status into consideration before performing an SBT in
      mechanically ventilated patients. METHODS: This was a prospective, observational
      study which included 355 mechanically ventilated patients. Daily assessments were
      made of whether the patients met criteria for performing a SBT. On the day a
      patient met the criteria, the level of sedation was evaluated using the Glasgow
      Coma Scale as modified by Cook and Palma (GCS-Cook) and it was registered whether
      or not the physician carried out an SBT. RESULTS: Two hundred and four patients
      (57%) underwent an SBT on the day they met the criteria (cohort 1) and in 151
      patients (cohort 2) the SBT was delayed a median time of 1 day (interquartile
      range 1-2). There were differences in the GCS-Cook score on the day the criteria
      were met for performing an SBT (mean 13+/-3 points in cohort 1 versus 9+/-3
      points in cohort 2; P<0.001). There were differences (P<0.001) between the
      cohorts in days of intubation and length of stay in the intensive care unit.
      CONCLUSIONS: Neurological status/level of sedation is a factor in the decision
      whether or not to perform a spontaneous breathing trial.

PMID- 17011781
TI  - Posterior stabilized component increased femoral bone loss after total knee
      replacement. 5-year follow-up of 47 knees using dual energy X-ray absorptiometry.
AB  - After total knee replacement (TKR) bone mineral density (BMD) commonly decreases
      behind the anterior flange of the femoral component, which may increase the risk
      for supracondylar fracture. Our aim was to evaluate if changes in femoral design
      and joint area constraint had any effect on the postoperative bone remodeling in
      the distal femur. We used dual-energy X-ray absorptiometry in 47 knees up to 5
      years after operation with the AMK (DePuy, Johnson and Johnson Leeds, UK) TKR.
      The knees had been randomly allocated to receive a flat or a concave tibial
      insert with retention of the posterior cruciate ligament when preoperative
      deformity was less severe, and either a concave or a posterior-stabilized (PS)
      insert with resection of the posterior cruciate ligament when deformity was more
      pronounced. The most pronounced relative reduction (15-38%) in bone mineral
      density (BMD) was seen posterior to the anterior flange. There were no
      significant differences in relative change in BMD between flat and concave
      inserts. Knees operated with PS inserts had more reduction posterior to the
      flange than knees with concave inserts in the subgroup with more advanced
      preoperative deformity (23% and 38% respectively). Use of posterior stabilized
      insert may increase the risk of supracondylar fracture compared to concave insert
      in knees with advanced preoperative deformity.

PMID- 17011782
TI  - Design, synthesis, structure-activity relationship, and in vivo activity of
      azabicyclic aryl amides as alpha7 nicotinic acetylcholine receptor agonists.
AB  - A novel set of azabicyclic aryl amides have been identified as potent and
      selective agonists of the alpha7 nAChR. A two-pronged approach was taken to
      improve the potential hERG liability of previously disclosed alpha7 nAChR
      agonist, PNU-282,987, while maintaining the compound's other desirable
      pharmacological properties. The first approach involved further exploration of
      the aryl carboxylic acid fragment of PNU-282,987, while the second approach
      focused on modification of the azabicyclic amine portion of PNU-282,987. The best
      compounds from each series are characterized by rapid brain penetration, good
      oral bioavailability in rat, and demonstrate in vivo efficacy in a rat P50
      auditory sensory gating assay. At least one analog from each series (1h, 1o, 2a,
      9a, and 18a) shows an improved hERG safety profile over PNU-282,987.

PMID- 17011783
TI  - Characterisation of bicontinuous cubic liquid crystalline systems of phytantriol
      and water using cryo field emission scanning electron microscopy (cryo FESEM).
AB  - Cubosomes are a novel lipid particulate delivery system currently being
      investigated for drug delivery purposes. The present study investigates
      bicontinuous cubic liquid crystalline systems (bulk phase and cubosomes) formed
      by phytantriol and water using cryo field emission scanning electron microscopy
      (cryo FESEM). Previously cubosomes have been characterized by cryo transmission
      electron microscopy (cryo TEM) with small angle X-ray diffraction (SAXS)
      confirming the bicontinuous liquid crystalline type. Bulk cubic phase and
      cubosomes were prepared from phytantriol and Pluronic F127 and analysed using
      cryo FESEM and SAXS. The micrographs showed the cubic phase had a tortuous,
      bicontinuous nature with a non-intersecting network of water channels. The
      cubosomes also show the same underlying tortuous structure entirely consistent
      with that of the bulk cubic phase and closely resemble the mathematical
      description of cubosomes described using nodal surface representation. The
      structure of both systems was confirmed using SAXS as a bicontinuous cubic liquid
      crystalline phase with Pn3m geometry. Cryo FESEM provides valuable insights into
      the morphological features of bicontinuous cubic liquid crystalline systems. The
      unique details shown provide strength to support the nodal surface representation
      of bicontinuous cubic liquid crystalline systems. Cryo FESEM provides a new
      technique to complement cryo TEM and SAXS for investigating their structure and
      function.

PMID- 17011784
TI  - Immobilization of cobalt in collapsed non-irradiated and gamma-irradiated X
      zeolites.
AB  - Cobalt exchanged X zeolites were gamma irradiated and heated until the zeolite
      structure collapsed. Heating destroys the zeolite network as found by X-ray
      diffraction and 29Si, 27Al MAS NMR spectroscopy. Gamma irradiation treatment
      diminished the collapsing temperature of zeolite. Cobalt leaching from
      crystalline and amorphized zeolites was verified by ion exchange with NaCl
      solution. Results show that cobalt is not released from the amorphous materials.
      Furthermore adsorption of xenon and 129Xe NMR spectroscopy reveal that cobalt
      ions are heterogeneously distributed in the non irradiated amorphous materials.
      Gamma irradiation causes the mobility of cobalt in the amorphous materials
      resulting then in a more homogeneous distribution. Cobalt is, thus, retained
      safely in the amorphous materials.

PMID- 17011785
TI  - Purification, product characterization and kinetic properties of lipoxygenase
      from olive fruit (Olea europaea L.).
AB  - Lipoxygenase from olive fruit was purified to homogeneity for the first time
      after differential centrifugations and by hydrophobic chromatography. The enzyme
      had a molecular mass of 98 kDa and exhibited a maximal activity at pH 6.
      Lipoxygenase had a better affinity for linoleic acid (Km=82.44 microM) than for
      linolenic acid (Km = 306.26 microM). It is inhibited by linoleate:oxygen
      oxidoreductase (LOX) inhibitors like nordihydroguaiaretic acid (NDGA) or propyl
      gallate. The reaction product was 13-hydroperoxy octadecadienoic acid when
      linoleic acid was used as substrate.

PMID- 17011786
TI  - Tissue-engineered trachea: History, problems and the future.
AB  - This review tries to summarize the efforts over the past 20 years to construct a
      tissue-engineered trachea. After illustrating the main technical bottlenecks
      faced nowadays, we discuss what might be the solutions to these bottlenecks. You
      may find out why the focus in this research field shifts dramatically from the
      construction of a tubular cartilage tissue to reepithelialization and
      revascularization of the prosthesis. In the end we propose a novel concept of 'in
      vivo bioreactor', defined as the design of a perfusion system inside the
      scaffold, and explain its potential application in the construction of a tissue
      engineered trachea.

PMID- 17011787
TI  - Pharmacological and clinical evaluation of L-asparaginase in the treatment of
      leukemia.
AB  - L-Asparaginase is an effective antineoplastic agent, used in the acute
      lymphoblastic leukemia chemotherapy. It has been an integral part of combination
      chemotherapy protocols of pediatric acute lymphoblastic leukemia for almost 3
      decades. The potential of L-asparaginase as a drug of leukemia has been a matter
      of discussion due to the high rate of allergic reactions exhibited by the
      patients receiving the medication of this enzyme drug. Frequent need of
      intramuscular injection has been another disadvantage associated with the native
      preparation. However, of late these clinical complications seem to have been
      addressed by modified versions of L-asparaginase. PEG-L-asparaginase proves to be
      most effective in this regard. It becomes important to discuss the efficacy of L
      asparaginase as an antileukemic drug vis-a-vis these disadvantages. In this
      review, an attempt has been made to critically evaluate the pharmacological and
      clinical potential of various preparations of L-asparaginase as a drug.
      Advantages of PEG-L-asparaginase over native preparations and historical
      developments of therapy with l-asparaginase have also been outlined in the review
      below.

PMID- 17011789
TI  - Genetics of epidermodysplasia verruciformis: Insights into host defense against
      papillomaviruses.
AB  - Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis
      associated with a high risk of skin carcinoma. EV results from an abnormal
      susceptibility to infection by specific human papillomavirus (HPV) genotypes
      (beta-papillomaviruses) which include the potentially oncogenic HPV5. EV-specific
      HPVs are considered as harmless for the general population. EV was recently found
      to be caused by invalidating mutations in two adjacent, related, novel genes,
      EVER1/TMC6 and EVER2/TMC8. EVER genes encode transmembrane proteins located in
      the endoplasmic reticulum, which are likely to function as modifiers of ion
      transporters or channels and to be involved in signal transduction. It was
      proposed that EV was a primary defect of innate immunity. Our hypothesis is that
      EVER proteins act as restriction factors for EV-specific HPVs in keratinocytes,
      and that EV represents a primary deficiency of intrinsic immunity against certain
      papillomaviruses.

PMID- 17011788
TI  - Effect of atorvastatin on soluble CD14, CD40 Ligand, sE- and sP-selectins and MCP
      1 in patients with type 2 diabetes mellitus: relationship to cholesterol
      turnover.
AB  - Metabolic abnormalities frequently associated with type 2 diabetes, feature
      besides endothelial dysfunction a novel factor of low cholesterol absorption and
      high cholesterol synthesis. We hypothesized an association between endothelial
      dysfunction and disturbances in cholesterol turnover, predisposing advanced
      atherosclerosis in patients with type 2 diabetes. We studied 75 patients: 30 with
      type 2 diabetes, 30 non-diabetic subjects with a history of cardiovascular
      disease, and 15 healthy subjects. Plasma sterols, soluble adhesion molecules
      sCD14, sCD40 Ligand, monocyte chemo-attractant protein-1 (MCP-1), sE- and sP
      selectins were measured with and without atorvastatin therapy. The diabetic
      patients showed significantly higher levels of lathosterol and lower levels of
      sitosterol and campesterol. Non-diabetic subjects showed no significant
      differences in non-cholesterol based sterols. Plasma levels of hsCRP, sE- and sP
      selectins and MCP-1 were significantly increased in patients with diabetes. The
      plasma levels of sCD40L correlate significantly with clinical parameters of BMI
      and glycaemia, and the plasma levels of sP-selectin correlate significantly with
      parameters of glycaemia and HbA(1c). The diabetic patients without statin therapy
      showed a significant correlation of sE-selectin with the marker of cholesterol
      absorption-sitosterol and sitosterol/cholesterol ratio. The diabetic patients
      without statin therapy showed a significant inverse correlation of sP-selectin
      with the marker of cholesterol synthesis-lathosterol. Both relationships
      disappeared with statin treatment. We conclude that endothelial dysfunction in
      obese patients with type 2 diabetes mellitus and cardiovascular disease
      associates with obesity and glycaemic control. The relation of parameters of
      endothelial dysfunction (such as sP-selectin and sE-selectin) with cholesterol
      synthesis and absorption may be influenced by reverse cholesterol transport.

PMID- 17011790
TI  - Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from
      Trypanosoma cruzi.
AB  - Trypanosoma cruzi chagasin belongs to a recently discovered family of cysteine
      protease inhibitors found in lower eukaryotes and prokaryotes but not in mammals.
      Chagasin binds tightly to cruzain, the major lysosomal T. cruzi cysteine
      protease, involved with infectivity and survival of the parasite in mammalian
      host cells. In the scope of a project to characterize proteins diferentially
      expressed during T. cruzi metacyclogenesis, we have determined the crystal
      structure of chagasin, which is now the first X-ray structure of a chagasin-like
      cysteine protease inhibitor to be reported. The structure was solved by the SIRAS
      method and refined at 1.7A resolution and a comparison with the two NMR
      structures available revealed some differences in the loops involved in binding
      to cysteine proteases. The highly flexible loop 4 could be entirely modeled and
      residues 29-33 from loop 2 form a 3(10)-helix structure that may be important to
      stabilize the loop conformation. Chagasin crystal structure was docked to the
      highest resolution structure available of cruzain and a model of chagasin-cruzain
      interaction was analyzed. The knowledge of the chagasin crystal structure may
      contribute to the elucidation of the molecular mechanism involved in the
      inhibition of cruzain and other T. cruzi cysteine proteases.

PMID- 17011791
TI  - Different extraretinal neuronal mechanisms of smooth pursuit eye movements in
      schizophrenia: An fMRI study.
AB  - Smooth pursuit eye movements (SPEM) are necessary to follow slowly moving targets
      while maintaining foveal fixation. In about 50% of schizophrenic patients SPEM
      velocity is reduced. In this study we were interested in identifying the cortical
      mechanisms associated with extraretinal processing of SPEM in schizophrenic
      patients. During condition A, patients and healthy subjects had to pursue a
      constantly visible target (10 degrees /s). During condition B the target was
      blanked out for 1000 ms while subjects were instructed to continue SPEM. Eye
      movement data were assessed during scanning sessions by a limbus tracker. During
      condition A, reduced SPEM velocity in patients was associated with reduced
      activation of the right ventral premotor cortex and increased activation of the
      left dorsolateral prefrontal cortex, the right thalamus and the Crus II of the
      left cerebellar hemisphere. During condition B, SPEM velocity was reduced to a
      similar extent in both groups. While in patients a decrease in activation was
      observed in the right cerebellar area VIIIA, the activation of the right anterior
      cingulate, the right superior temporal cortex, and the bilateral frontal eye
      fields was increased. The results implicate that schizophrenic patients employ
      different strategies during SPEM both with and without target blanking than
      healthy subjects. These strategies predominantly involve extraretinal mechanisms.

PMID- 17011792
TI  - Smoothing and cluster thresholding for cortical surface-based group analysis of
      fMRI data.
AB  - Cortical surface-based analysis of fMRI data has proven to be a useful method
      with several advantages over 3-dimensional volumetric analyses. Many of the
      statistical methods used in 3D analyses can be adapted for use with surface-based
      analyses. Operating within the framework of the FreeSurfer software package, we
      have implemented a surface-based version of the cluster size exclusion method
      used for multiple comparisons correction. Furthermore, we have a developed a new
      method for generating regions of interest on the cortical surface using a sliding
      threshold of cluster exclusion followed by cluster growth. Cluster size limits
      for multiple probability thresholds were estimated using random field theory and
      validated with Monte Carlo simulation. A prerequisite of RFT or cluster size
      simulation is an estimate of the smoothness of the data. In order to estimate the
      intrinsic smoothness of group analysis statistics, independent of true
      activations, we conducted a group analysis of simulated noise data sets. Because
      smoothing on a cortical surface mesh is typically implemented using an iterative
      method, rather than directly applying a Gaussian blurring kernel, it is also
      necessary to determine the width of the equivalent Gaussian blurring kernel as a
      function of smoothing steps. Iterative smoothing has previously been modeled as
      continuous heat diffusion, providing a theoretical basis for predicting the
      equivalent kernel width, but the predictions of the model were not empirically
      tested. We generated an empirical heat diffusion kernel width function by
      performing surface-based smoothing simulations and found a large disparity
      between the expected and actual kernel widths.

PMID- 17011793
TI  - Normal and abnormal fMRI activation patterns in the visual cortex after recovery
      from optic neuritis.
AB  - Recovery to normal or near normal visual acuity after an optic neuritis episode
      is common, despite frequent persistence of conduction abnormalities, evident in
      prolonged visual evoked potential (VEP) latencies. Improvement of visual function
      is commonly attributed to peripheral nerve recovery. However, central
      reorganization processes may also be involved. To assess this, we compared the
      patterns of fMRI activation, elicited by stimulation of the affected and the
      normal eye, along the visual cortical hierarchy. Activation was assessed in 8
      subjects, which recovered clinically from an episode of optic neuritis but still
      had prolonged VEP latencies. In all patients, reduced fMRI activation was seen in
      V1 during stimulation of the affected eye, compared to the normal eye. The fMRI
      signal difference decreased in magnitude with progression along the visual
      hierarchy, and in some regions within the lateral occipital complex even showed
      the opposite preference (for the affected eye). These results may indicate a
      built-in robustness of the object-related areas to disruption of the visual
      input. Alternatively, it could reflect an adaptive functional reorganization of
      the cortical response to an abnormal input.

PMID- 17011794
TI  - How should gaps be treated in parsimony? A comparison of approaches using
      simulation.
AB  - Simulation with indels was used to produce alignments where true site homologies
      in DNA sequences were known; the gaps from these datasets were removed and the
      sequences were then aligned to produce hypothesized alignments. Both alignments
      were then analyzed under three widely used methods of treating gaps during tree
      reconstruction under the maximum parsimony principle. With the true alignments,
      for many cases (82%), there was no difference in topological accuracy for the
      different methods of gap coding. However, in cases where a difference was
      present, coding gaps as a fifth state character or as separate presence/absence
      characters outperformed treating gaps as unknown/missing data nearly 90% of the
      time. For the hypothesized alignments, on average, all gap treatment approaches
      performed equally well. Data sets with higher sequence divergence and more
      pectinate tree shapes with variable branch lengths are more affected by gap
      coding than datasets associated with shallower non-pectinate tree shapes.

PMID- 17011795
TI  - Genetic differentiation and cryptic speciation in natural populations of
      Drosophila lacertosa.
AB  - Drosophila lacertosa, an Oriental member of the robusta species group in the
      virilis-repleta radiation, has a wide distribution from northern India throughout
      China to the Far East. Phylogenetic analyses of mitochondrial ND2 gene sequences
      revealed two genetically significantly diverged lineages with 2.1% DNA sequence
      divergence. These two lineages are largely allopatric: one is mainly found in
      southwest China (lineage A), whereas the other ranges central and east of China
      to northeast Asia (lineage B). The geographic distributions of these two clades
      narrowly overlap near the provincial boundaries of Yunnan and Guizhou or Guangxi,
      probably as a consequence of population expansion and secondary contact. These
      two lineages were estimated to have diverged about 0.56 Mya, and the estimated
      time of expansion was approximately 70,000 years ago for lineage A population,
      and 110,000 years ago for lineage B population. The present molecular analysis,
      together with nearly complete reproductive isolation between those two lineages,
      strongly suggests that the two lineages might be incipient species.

PMID- 17011796
TI  - An island in the stream: Australia's place in the cosmopolitan world of Indo-West
      Pacific freshwater shrimp (Decapoda: Atyidae: Caridina).
AB  - Mitochondrial DNA sequences were used to investigate phylogenetic and
      biogeographic relationships among Australian freshwater shrimp from the genus
      Caridina H. Milne Edwards, 1837 (Atyidae) and congeners from potential source
      populations throughout the Indo-West Pacific region. Numerous Australian taxa
      have close evolutionary relationships with non-Australian taxa from locations
      throughout the region, indicating a diverse origin of the Australian freshwater
      fauna. This implies many colonisations to or from Australia over a long period,
      and thus highlights the surprising adeptness of freshwater shrimp in dispersal
      across ocean barriers and the unity of much of the region's freshwater biota.
      Interestingly, a study on Australia's other main genus of atyid shrimp, Paratya
      Miers, 1882, inferred only a single colonisation. A number of potential species
      radiations within Australia were also identified. This agrees with patterns
      detected for a large number of Australian freshwater taxa, and so implies a
      vicariant explanation due to the development of colder, dryer climates during the
      late Miocene/early Pliocene.

PMID- 17011798
TI  - Fluid temperatures during radiofrequency use in shoulder arthroscopy: a cadaveric
      study.
AB  - Cadaveric shoulders underwent thermal capsulorrhaphy and subacromial
      decompression with 3 different commercially available radiofrequency (RF) devices
      to evaluate local and regional fluid temperatures while arthroscopic procedures
      were being performed. Fifteen completely thawed fresh-frozen shoulders underwent
      both thermal capsulorrhaphy and subacromial decompression. During thermal
      capsulorrhaphy, Fluoroptic mini-thermometer probes (Luxtron model 3000) were
      placed in the inflow bag; in the glenohumeral joint, near the inferior
      glenohumeral ligament; and on the RF wand. During subacromial decompression, the
      temperature probes were placed in the anterior and posterior subacromial space,
      as well as in the inflow bag and on the RF wand. All data were initially analyzed
      by use of analysis of variance, followed by pairwise comparison, adjusted for
      multiple testing by use of the Scheffe method. Mean fluid temperatures (in
      degrees Celsius [+/- SD]) were highest at the RF wand during both capsulorrhaphy
      and subacromial decompression. Mean fluid temperatures were much lower at other
      recorded sites. In this model, we show no deleterious elevation in arthroscopic
      fluid temperature while performing thermal capsulorrhaphy or subacromial
      decompression using any of the 3 devices at their recommended settings.

PMID- 17011799
TI  - The ethics of excluding women who become pregnant while participating in clinical
      trials of anti-epileptic medications.
AB  - INTRODUCTION: The bioethical principles of autonomy, beneficence, non-maleficence
      and justice, complemented by ethics committee evaluation, define conduct of
      clinical trials of anti-epileptic medications (AEM). BACKGROUND INFORMATION:
      Increased teratogenicity for offspring of women with epilepsy is presented in
      both lay and scientific literature. SPECIFIC DRUGS--OLDER GENERATION:
      Teratogenicity of phenobarbitone (PB), phenytoin (PHT), valproate (VPA) and
      carbamazepine (CBZ) is acknowledged, with drugs, such as trimethadione, being
      removed from the market because of teratogenicity. SPECIFIC DRUGS--NEW
      GENERATION: Insufficient data allowed definitive commentary concerning
      teratogenicity of newer AEM, such as lamotrigine (LTG), gabapentin (GBP),
      tiagabine (TGB) or levetiracetam (LEV). All those suggestions favour some over
      others with specific AEM combinations being questioned. PREGNANCY REGISTRIES:
      Lack of information sporn AEM-specific plus national and international birth
      registries which endorse VPA, CBZ and LTG dose related concerns. CONFLICT OF
      INTEREST: Competing influences of AEM and epilepsy-specific factors need
      delineation although appear more teratogenetic than does epilepsy alone. CLINICAL
      TRIALS: Most trials focus upon refractory epilepsy with potentially enhanced
      risks. Informed consent demands discussion of possible teratogenicity and
      exclusion of women unwilling to practice adequate contraception. DISCUSSION:
      Trials must respect legal and ethical dictates including the exclusion of women
      unwilling to practice reliable contraception. Automatic exclusion from a trial,
      subsequent to confirmed pregnancy, is unlikely to protect the foetus as potential
      for teratogenicity already has occurred. Autonomy should empower prospective
      parents to decide continued trial participation consequent to detailed informed
      consent without coercion. All options demand review, including responsibility to
      future AEM users.

PMID- 17011797
TI  - Evolution of the planthoppers (Insecta: Hemiptera: Fulgoroidea).
AB  - The planthopper superfamily Fulgoroidea (Insecta: Hemiptera) comprises
      approximately 20 described insect families, depending on which classification is
      followed. Multiple competing hypotheses of fulgoroid phylogeny have been
      published, based on either morphological character coding or DNA sequence data;
      however, those hypotheses disagree in several key aspects regarding the evolution
      of planthoppers. The current paper seeks to test these hypotheses, including the
      Asche (Asche, M. 1987. Preliminary thoughts on the phylogeny of Fulgoromorpha
      (Homoptera Auchenorrhyncha). In: Proceedings of the 6th Auchenorrhyncha Meeting,
      Turin, Italy, 7-11 September, 1987, pp. 47-53.) hypothesis of a trend in
      ovipositor structure, which may be correlated with planthopper feeding ecology.
      Presented here are phylogenetic reconstructions of Fulgoroidea based on analysis
      of DNA nucleotide sequence data from four loci (18S rDNA, 28S rDNA, Histone 3,
      and Wingless) sequenced from 83 exemplar taxa representing 18 planthopper
      families and outgroups. Data sets were analyzed separately and in various
      combinations under the maximum parsimony criterion, and the total combined
      dataset was analyzed via both maximum parsimony and partitioned Bayesian
      criteria; results of the combined analyses were concordant across reconstruction
      paradigms. Relationships recovered suggest several major planthopper lineages,
      including: (1) Delphacidae+Cixiidae; (2) Kinnaridae+Meenoplidae; (3)
      Fulgoridae+Dictyopharidae; (4) Lophopidae+Eurybrachidae (possibly+Flatidae); (5)
      Ricaniidae+Caliscelidae (possibly+Tropiduchidae). Results also suggest the
      placement of Achilixiidae outside of Cixiidae and of Tettigometridae as one of
      the more recently diversified lineages within Fulgoroidea. The resulting
      phylogeny supports Asche's (1987) hypothesis of a functional trend in ovipositor
      structure across families.

PMID- 17011800
TI  - Human hyaluronidase-2 is localized intracellularly in articular chondrocytes and
      other cultured cell lines.

PMID- 17011801
TI  - Imbalance in SOD/CAT activities in rat skeletal muscles submitted to treadmill
      training exercise.
AB  - The association between physical exercise and oxidative damage in the skeletal
      musculature has been the focus of many studies in literature, but the balance
      between superoxide dismutase and catalase activities and its relation to
      oxidative damage is not well established. Thus, the aim of the present study was
      to investigate the association between regular treadmill physical exercise,
      oxidative damage and antioxidant defenses in skeletal muscle of rats. Fifteen
      male Wistar rats (8-12 months) were randomly separated into two groups (trained
      n=9 and untrained n=6). Trained rats were treadmill-trained for 12 weeks in
      progressive exercise (velocity, time, and inclination). Training program
      consisted in a progressive exercise (10 m/min without inclination for 10
      min/day). After 1 week the speed, time and inclination were gradually increased
      until 17 m/min at 10% for 50 min/day. After the training period animals were
      killed, and gastrocnemius and quadriceps were surgically removed to the
      determination of biochemical parameters. Lipid peroxidation, protein oxidative
      damage, catalase, superoxide dismutase and citrate synthase activities, and
      muscular glycogen content were measured in the isolated muscles. We demonstrated
      that there is a different modulation of CAT and SOD in skeletal muscle in trained
      rats when compared to untrained rats (increased SOD/CAT ratio). TBARS levels were
      significantly decreased and, in contrast, a significant increase in protein
      carbonylation was observed. These results suggest a non-described adaptation of
      skeletal muscle against exercise-induced oxidative stress.

PMID- 17011802
TI  - Effect of chronic angiotensin converting enzyme inhibition on spatial memory and
      anxiety-like behaviours in rats.
AB  - Angiotensin converting enzyme inhibitors (ACEis) are widely used anti
      hypertensive agents that are also reported to have positive effects on mood and
      cognition. The present study examined the influence of the ACEi, perindopril, on
      cognitive performance and anxiety measures in rats. Two groups of rats were
      treated orally for one week with the ACEi, perindopril, at doses of 0.1 and
      1.0mg/kg/day. Learning was assessed by the reference memory task in the water
      maze, comparing treated to control rats. Over five training days both perindopril
      treated groups learnt the location of the submerged platform in the water maze
      task significantly faster than control rats. A 60s probe trial on day 6 showed
      that the 1.0mg/kg/day group spent significantly longer time in the training
      quadrant than control rats. This improved performance in the swim maze task was
      not due to the effect of perindopril on motor activity or the anxiety levels of
      the rats as perindopril-treated and control animals behaved similarly in activity
      boxes and on the elevated+maze. These results confirm the anecdotal human studies
      that ACEis have a positive influence on cognition and provide possibilities for
      ACEis to be developed into therapies for memory loss.

PMID- 17011803
TI  - Methylene blue facilitates the extinction of fear in an animal model of
      susceptibility to learned helplessness.
AB  - The objectives were to (1) extend previous findings on fear extinction deficits
      in male congenitally helpless rats (a model for susceptibility to learned
      helplessness) to female congenitally helpless rats, and (2) attempt a therapeutic
      intervention with methylene blue, a metabolic enhancer that improves memory
      retention, to alleviate the predicted extinction deficits. In the first
      experiment, fear acquisition (four tone-shock pairings in operant chamber) was
      followed by extinction training (60 tones in open field). Congenitally helpless
      rats showed fear acquisition similar to controls but had dramatic extinction
      deficits, and did not display the gradual extinction curves observed in controls.
      Congenitally helpless rats demonstrated greater tone-evoked freezing as compared
      to controls in both the acquisition and extinction contexts one week after
      extinction training, and also in the extinction probe conducted one month later.
      In the second experiment (which began one month after the first experiment)
      congenitally helpless subjects were further exposed to tones for 5 days, each
      followed by 4 mg/kg methylene blue or saline IP, and had a fear renewal test in
      the acquisition context. Methylene blue administration improved retention of the
      extinction memory as demonstrated by significant decreases in fear renewal as
      compared to saline-administered congenitally helpless subjects. The impaired
      ability to extinguish fear to a traumatic memory in congenitally helpless rats
      supports the validity of this strain as an animal model for vulnerability to post
      traumatic stress disorder, and this study further suggests that methylene blue
      may facilitate fear extinction as an adjunct to exposure therapy.

PMID- 17011804
TI  - The influence of cholesterol, progesterone, 4-androstenedione and testosterone on
      the growth of Treponema denticola ATCC 33520 in batch cultures.
AB  - Previously, we have shown that reference and freshly isolated Treponema denticola
      cultures are capable of metabolising cholesterol, progesterone, 4-androstenedione
      and testosterone by means of 5alpha-reductase, 3beta-and 17beta-hydroxysteroid
      dehydrogenase activity [Clark DT, Soory M. The metabolism of cholesterol and
      certain hormonal steroids by Treponema denticola. Steroids. 2006;71:352-63. ].
      The aim of the work presented in this paper was to investigate the modulation of
      T. denticola growth in batch cultures by these steroids, using T. denticola ATCC
      33520 as a model system. Growth curves were summarised using statistics based on
      optical density and protein yield. Cholesterol was found to stimulate growth at
      concentrations of 10 and 25microg/mL. Certain hormonal steroids inhibited the
      maximum achievable optical density at concentrations of 1 and 10microg/mL while
      the minimum concentration shown to inhibit protein yield was 0.001microg/mL of
      progesterone. The potential of the hormonal steroids to inhibit growth was in the
      order of progesterone, 4-androstenedione and testosterone.

PMID- 17011805
TI  - A rapid assay of the sialidase activity in species of the Bacteroides fragilis
      group by using peanut lectin hemagglutination.
AB  - In this study, a novel, simple and rapid hemagglutination assay by using a peanut
      lectin to detect a neuraminidase activity in strains of the Bacteroides fragilis
      group was developed. One hundred and fourteen species of the B. fragilis group
      isolated from children with and without diarrhea and 15 reference strains were
      evaluated. Neuraminidase production was determined by using the method above
      described and its inhibition was observed by using galactose. The neuraminidase
      production was observed in 54 (84.37%) diarrhea and in 43 (86%) non-diarrhea
      strains. HA titers were ranged from 2 to 32. This neuraminidase assays based on
      PNA hemagglutination is highly sensitive, reproducible and could be used as a
      tool to detect the sialidase activity in anaerobic bacteria, particularly, in
      species of the B. fragilis group.

PMID- 17011806
TI  - Three hydrolases and a transferase: comparative analysis of active-site dynamics
      via the BioSimGrid database.
AB  - Comparative molecular dynamics (MD) simulations enable us to explore the
      conformational dynamics of the active sites of distantly related enzymes. We have
      used the BioSimGrid (http://www.biosimgrid.org) database to facilitate such a
      comparison. Simulations of four enzymes were analyzed. These included three
      hydrolases and a transferase, namely acetylcholinesterase, outer-membrane
      phospholipase A, outer-membrane protease T, and PagP (an outer-membrane enzyme
      which transfers a palmitate chain from a phospholipid to lipid A). A set of 17
      simulations were analyzed corresponding to a total of approximately 0.1 micros
      simulation time. A simple metric for active-site integrity was used to
      demonstrate the existence of clusters of dynamic conformational behaviour of the
      active sites. Small (i.e. within a cluster) fluctuations appear to be related to
      the function of an enzymatically active site. Larger fluctuations (i.e. between
      clusters) correlate with transitions between catalytically active and inactive
      states. Overall, these results demonstrate the potential of a comparative MD
      approach to analysis of enzyme function. This approach could be extended to a
      wider range of enzymes using current high throughput MD simulation and database
      methods.

PMID- 17011807
TI  - Effects of swimming training on bone mass and the GH/IGF-1 axis in diabetic rats.
AB  - The aim of this study was to examine the influence of moderate swimming training
      on the GH/IGF-1 growth axis and tibial mass in diabetic rats. Male Wistar rats
      were allocated to one of four groups: sedentary control (SC), trained control
      (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced
      with alloxan (35 mg/kg b.w.). The training program consisted of a 1h swimming
      session/day with a load corresponding to 5% of the b.w., five days/week for six
      weeks. At the end of the training period, the rats were sacrificed and blood was
      collected for quantification of the serum glucose, insulin, GH, and IGF-1
      concentrations. Samples of skeletal muscle were used to quantify the IGF-1
      peptide content. The tibias were collected to determine their total area, length
      and bone mineral content. The results were analyzed by ANOVA with P<0.05
      indicating significance. Diabetes decreased the serum levels of GH and IGF-1, as
      well as the tibial length, total area and bone mineral content in the SD group
      (P<0.05). Physical training increased the serum IGF-1 level in the TC and TD
      groups when compared to the sedentary groups (SC and SD), and the tibial length,
      total area and bone mineral content were higher in the TD group than in the SD
      group (P<0.05). Exercise did not alter the level of IGF-1 in gastrocnemius muscle
      in nondiabetic rats, but the muscle IGF-1 content was higher in the TD group than
      in the SD group. These results indicate that swimming training stimulates bone
      mass and the GH/IGF-1 axis in diabetic rats.

PMID- 17011808
TI  - Chronic osteomyelitis of clavicle as primary manifestation of SAPHO syndrome in
      adolescents: report of four cases and long-term evolution.
AB  - Four cases of chronic osteomyelitis of clavicle as primary manifestation of
      synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) are reported in
      adolescents. In all cases a typical radiographical evolution had been observed
      with progressive slow migration of sclerotic area from medial to lateral side of
      clavicle. Long-term evolution was alternation of remission and exacerbation but
      none of the patients healed.

PMID- 17011809
TI  - Model of arterial tree and peripheral control for the study of physiological and
      assisted circulation.
AB  - Peripheral vasomotion, interstitial liquid exchange, and cardiovascular system
      behaviour are investigated by means of a lumped parameter model of the systemic
      and peripheral circulation, from the aortic valve to the venules. This modelling
      work aims at combining arterial tree hemodynamics description, active peripheral
      flow regulation, and fluid exchange. The arterial compartment is constructed with
      63 RCL segments and 30 peripheral districts including myogenic control on
      arterioles, metabolic control on venules, and Starling filtration through
      capillary membrane. The arterial behaviour is characterised as to the long term
      stability of pressure/flow waves in the different segments. Peripheral districts
      show autoregulatory capabilities against pressure changes over a wide range and
      also self-sustained oscillations mimicking vasomotor activity. A preliminary
      study was carried out as to the model response to changes induced by
      cardiopulmonary bypass (CPB). Among the induced alterations, the system responds
      mainly to hemodilution, which increased peripheral fluid loss and oedema beyond
      the compensatory capabilities of local regulation mechanisms. This resulted in an
      overall increase total arterial resistance. Local transport deficits were
      assessed for each district according to the different metabolic demand. This
      study shows the requirement of a suitable description of both arteries and
      peripheral mechanisms in order to describe cardiovascular response non
      physiological conditions, as well as assisted circulation or other pathological
      conditions.

PMID- 17011810
TI  - Assessment of abuse-related injuries: a comparative study of forensic physicians,
      emergency room physicians, emergency room nurses and medical students.
AB  - A comparative study was made investigating whether emergency room physicians,
      emergency room nurses, forensic physicians, and interns are competent in
      describing, recognising and determining the possible cause of injuries. The
      injury assessment scores varied from good--adequate--fail and remained blank in
      various participant groups. Forensic physicians scored significantly better than
      emergency room staff and interns in the assessment of abuse-related injuries.
      There were almost no differences noted between emergency room physicians and
      emergency room nurses. For the functional group with more or less than 4 to 6
      years of experience, no significant differences were noted for scoring good in
      all 5 cases. The fact that forensic physicians scored better than the emergency
      room staff is probably explained by the fact that almost all practicing forensic
      physicians have been officially qualified. Training in this field for all
      professionals involved in such assessment should be mandatory.

PMID- 17011812
TI  - Ectomesenchymal chondromyxoid tumour of the tongue: Unlikely to originate from
      myoepithelial cells.
AB  - Ectomesenchymal chondromyxoid tumour is a recently described rare entity found
      almost exclusively in the anterior dorsum of the tongue. We report an additional
      case, review the pertinent literature and explore the histogenesis of the lesion.
      The lesion has no discriminating clinical features and diagnosis is only
      established following histopathological examination including immunohistochemical
      assessment. The histogenesis of the lesion remains speculative and our study
      seems to discount myoepithelial cells as a potential source.

PMID- 17011811
TI  - Methods and biomarkers for the diagnosis and prognosis of cancer and other
      diseases: towards personalized medicine.
AB  - The rapid development of new diagnostic procedures, the mapping of the human
      genome, progress in mapping genetic polymorphisms, and recent advances in nucleic
      acid- and protein chip technologies are driving the development of personalized
      therapies. This breakthrough in medicine is expected to be achieved largely due
      to the implementation of "lab-on-the-chip" technology capable of performing
      hundreds, even thousands of biochemical, cellular and genetic tests on a single
      sample of blood or other body fluid. Focusing on a few disease-specific examples,
      this review discusses selected technologies and their combinations likely to be
      incorporated in the "lab-on-the-chip" and to provide rapid and versatile
      information about specific diseases entities. Focusing on breast cancer and after
      an overview of single-nucleotide polymorphism (SNP)-screening methodologies, we
      discuss the diagnostic and prognostic importance of SNPs. Next, using Duchenne
      muscular dystrophy (DMD) as an example, we provide a brief overview of powerful
      and innovative integration of traditional immuno-histochemistry techniques with
      advanced biophysical methods such as NMR-spectroscopy or Fourier-transformed
      infrared (FT-IR) spectroscopy. A brief overview of the challenges and
      opportunities provided by protein and aptamer microarrays follows. We conclude by
      highlighting novel and promising biochemical markers for the development of
      personalized treatment of cancer and other diseases: serum cytochrome c,
      cytokeratin-18 and -19 and their proteolytic fragments for the detection and
      quantitation of malignant tumor mass, tumor cell turn-over, inflammatory
      processes during hepatitis and Epstein-Barr virus (EBV)-induced hemophagocytic
      lymphohistiocytosis and apoptotic/necrotic cancer cell death.

PMID- 17011813
TI  - Biosynthesis of plant cell wall polysaccharides - a complex process.
AB  - Cellulose, a major component of plant cell walls, is made by dynamic complexes
      that move within the plasma membrane while depositing cellulose directly into the
      wall. On the other hand, matrix polysaccharides are made in the Golgi and
      delivered to the wall via secretory vesicles. Several Golgi proteins that are
      involved in glucomannan and xyloglucan biosynthesis have been identified,
      including some glycan synthases that show sequence similarity to the cellulose
      synthase proteins and several glycosytransferases that add sidechains to the
      polysaccharide backbones. Recent progress in identifying the proteins needed for
      polysaccharide biosynthesis should lead to an improved understanding of the
      molecular details of these complex processes, and eventually to an ability to
      manipulate them in an effort to generate plants that have improved properties for
      human uses.

PMID- 17011814
TI  - The ins and outs of plant cell walls.
AB  - New findings reveal that many membrane proteins undergo regulated trafficking
      between intracellular compartments and the plasma membrane. This also appears to
      be a common regulatory mechanism in the control of cell wall metabolism.

PMID- 17011815
TI  - Dynamics of photosynthesis in fluctuating light.
AB  - Our understanding of the molecular mechanisms of plant photosynthesis is
      expanding from insights into static fluxes in constant irradiance to an
      understanding of complex dynamic patterns in fluctuating light. Knowledge about
      regulatory interactions, information about relevant biological features that
      emerge in fluctuating light, and the new standards for sharing biological models
      allow world-wide consortia aimed at the comprehensive modeling of photosynthetic
      dynamics.

PMID- 17011816
TI  - Endocytosis in signalling and development.
AB  - After a long period of neglect, endocytosis in plants is finally coming of age.
      The constitutive recycling of plasma membrane proteins has been well established
      in the past few years, and recent studies report the ligand-induced endocytosis
      of receptors and other plasma membrane proteins. Signalling by ligand-bound
      receptors from endosomes has not, however, been demonstrated in plants. Although
      novel markers have been used to map endocytic pathways, the functional
      compartmentalisation of endosomes is still controversial. It is thus not clear
      where and how cargo proteins such as receptors are sorted towards either
      recycling to the plasma membrane or targeting to the vacuole for degradation.

PMID- 17011817
TI  - Spectroscopic studies on the inclusion complex of 2-naphthol-6-sulfonate with
      beta-cyclodextrin.
AB  - The photophysical properties of 2-naphthol-6-sulfonate (2-NOH-6-S) in various
      solvents and in aqueous beta-cyclodextrin solution have been investigated. The
      fluorescence quantum yields in non-aqueous solvents are approximately 0.20+/
      0.02, while in water the yield is higher. The fluorescence quantum yield in water
      was found to depend on the pH value of the medium and increases as the pH
      increase up to a pH value of 4.0 where it comes to be constant. Absorption and
      fluorescence measurements show 1:1 inclusion of 2-NOH-6-S in the beta
      cyclodextrin cavity. The association constant of 2-NOH-6-S-beta-cyclodextrin
      complex based on fluorescence measurements was calculated using Benesi-Hildbrand
      relationship and found to be 330+/-30M(-1). (1)H NMR studies are used to confirm
      the inclusion and to provide information on the geometry of 2-NOH-6-S inside the
      cavity of beta-cyclodextrin.

PMID- 17011818
TI  - DNA interaction with Al-N,N'-bis(salicylidene)2,2'-phenylendiamine complex.
AB  - The Al(III) complex, [Al(salophen)2H2O]NO3, was synthesized and characterized by
      spectroscopic (NMR and FT-IR) techniques. Then the binding of Schiff base complex
      of [Al(salophen)]+ type, where salophen denotes N,N'-bis(salicylidene) 2,2
      phenylendiamine to calf thymus DNA, has been investigated by spectrophotometric,
      circular dichroism, spectrofluorometric, melting temperature and viscosimetric
      techniques. This Al(III) complex showed absorption hyperchromism in the range of
      310-390 nm, increase in melting temperature, some structural changes in specific
      viscosity, when bound to calf thymus DNA. The binding constant has been
      determined using absorption measurement and found to be 1.82 x 10(3)M(-1) and
      1.31 x 10(3)M(-1) in HEPES and Tris-HCl buffers, respectively. Also the
      fluorescence spectral characteristics and interaction of Al-salophen complex with
      DNA have been studied. Al-salophen bound to DNA showed a marked increase in the
      fluorescence intensity along with a bathochromic shift (5 nm). The intersection
      point of the binding isotherm indicated a binding site size of 12 bp per bound
      complex molecule in both HEPES and Tris-HCl buffers. The experimental results
      showed that the Al-salophen complex bound to DNA by non-intercalative mode and
      major groove binding was the preferred mode of interaction.

PMID- 17011819
TI  - Molecular probes for sensing the cholesterol composition of subcellular organelle
      membranes.
AB  - Neuroendocrine cells contain two types of secretagogue-regulated acidic
      compartments: secretory granules (SGs) and synaptic-like microvesicles (SLMVs),
      which can be identified by acidotropic probes such as acridine orange (AO) and
      DAMP. We investigated the accumulation of these probes in SGs and SLMVs as a
      function of glucose levels in the culture media using a pancreatic beta-cell line
      MIN6. AO was accumulated in the low-glucose condition, but not in the high
      glucose condition. The AO accumulation correlated well with the SLMV dynamics by
      glucose and DAMP was localized in the SGs. Because SG membranes are reportedly
      high in cholesterol, we prepared liposomes with increasing cholesterol levels. AO
      is well incorporated into liposomes having a 20 to 40 mol% cholesterol
      composition, whereas DAMP was so in those having over 40 mol% cholesterol levels.
      Indeed, when cholesterol was depleted from MIN6 SG membranes, DAMP incorporation
      decreased, instead AO was incorporated. In PC12 cells, AO incorporation into SGs
      was significant but DAMP incorporation was limited. Consistently, the cholesterol
      composition was found 37 to 39 mol% in the SG membrane of PC12 cells. We suggest
      that cholesterol-sensing probes, AO and DAMP, are useful tools for investigating
      cholesterol compositions in acidic organelle membranes.

PMID- 17011820
TI  - EEG dipole analysis of motor-priming foreperiod activity reveals separate sources
      for motor and spatial attention components.
AB  - OBJECTIVE: This study employed EEG source localisation procedures to study the
      contribution of motor preparatory and attentional processing to foreperiod
      activity in an S1-S2 motor priming task. METHODS: Behavioural and high-density
      event-related potential (ERP) data were recorded in an S1-S2 priming task where
      participants responded to S2 with a left or right-hand button press. S1 either
      provided information about response hand (informative) or ambiguous information
      (uninformative). RESULTS: Responses were significantly faster in informative
      trials compared with uninformative trials. Dipole source analysis of foreperiod
      lateralized ERPs revealed sources of motor preparatory activity in the
      dorsolateral premotor cortex (PMd) in line with previous work. In addition, two
      spatial attention components (ADAN, LDAP) were identified with generators in the
      PMd and occipitotemporal visual areas in the middle temporal (MT) region,
      respectively. Separation of motor-related and attentional PMd source locations
      was reliable along the rostral-caudal axis. CONCLUSIONS: The presence of
      attentional components in a motor priming paradigm supports the premotor theory
      of attention which suggests a close link between attention and motor preparatory
      processes. Separation of components in the premotor cortex is in accord with a
      functional division of PMd into rostral (higher-order processing) and caudal
      (motor-related processing) areas as suggested by imaging work. SIGNIFICANCE: A
      prime for response preparation is a trigger for separate, but closely linked,
      attention-related activity in premotor areas.

PMID- 17011821
TI  - Modulation of corticospinal excitability by paired associative stimulation:
      reproducibility of effects and intraindividual reliability.
AB  - OBJECTIVE: Electrical stimulation of the median nerve followed by a magnetic
      pulse on the primary motor cortex (M1) is effective to cause an increase in the
      amplitude of motor evoked potential (MEP) registered in the target muscle with
      the interstimulus interval (ISI) at 25ms (paired associative stimulation, PAS).
      The aim of this study is to evaluate the reproducibility of PAS with ISI 25
      (PAS25), assessed in two separate sessions. Intraindividual reliability of TMS
      measures was also evaluated. METHODS: Motor threshold of abductor pollicis brevis
      (APB), assessed at rest, and MEP amplitude of APB and abductor digiti minimi
      (ADM) were assessed before and after PAS25 in 18 healthy volunteers (nine males
      and nine females). RESULTS: Data showed a significant increase of MEP amplitude
      in the target muscle (APB) after PAS25 and a reproducibility of group effect in
      the two sessions, as assessed by ANOVA, but a lack of intraindividual
      reliability, as assessed by intraclass correlation coefficients (ICC).
      CONCLUSIONS: The results underline the reproducibility of mean effects and the
      need to be careful when comparing the same subject on different days.
      SIGNIFICANCE: Electrical stimulation of the median nerve followed by a magnetic
      pulse delivered on M1 after 25ms causes a reproducible increase in MEP amplitude,
      without showing an acceptable intraindividual reliability.

PMID- 17011822
TI  - Differential effect of serum from bipolar versus schizophrenic patients on
      spontaneous acetylcholine release at mammalian neuromuscular junction.
AB  - OBJECTIVE: The diagnosis of bipolar disease frequently requires a long time since
      the age of onset, especially because the disease is misdiagnosed with
      schizophrenia. The aim of the present work was to investigate whether sera from
      bipolar patients have an active substance that allows making a fast
      identification of the disease. METHODS: Sera from healthy volunteers, euthymic
      and non-stabilized bipolar patients, and schizophrenic patients were passively
      transferred into CF1 mice and after 2 day injections, MEPP frequency from
      diaphragm muscles was recorded. The same procedure was performed with sera
      fraction of high and low MW (cut-off 3000). RESULTS: Sera from non-stabilized
      bipolar patients induced a decreased MEPP frequency and occluded the presynaptic
      inhibitory effect of the specific adenosine A(1) receptor agonist 2-chloro-N(6)
      cyclopentyl-adenosine (CCPA) in the recipient mice, while in the euthymic bipolar
      group spontaneous secretion reached control values although the action of CCPA
      was still prevented. Similar results were obtained with low MW sera fraction from
      euthymic and non-stabilized bipolar patients. The addition of adenosine deaminase
      to the sera fraction prevented the modification of spontaneous ACh release. In
      mice injected with sera from schizophrenic patients, MEPP frequency was within
      control values and CCPA induced its typical inhibitory action. CONCLUSIONS: These
      results indicate that bipolar patients contain in their blood an active substance
      compatible with adenosine, which was able to modify spontaneous ACh release in
      the recipient mice. This effect was not observed with sera from healthy
      volunteers and schizophrenic patients. The increase of adenosine concentration
      may result from synaptic hyperactivity that presumably plays a role in the
      symptoms of bipolar disorder and/or may derive from peripheral cells through a
      more general mechanism. SIGNIFICANCE: The different results obtained with bipolar
      and schizophrenic sera raise the possibility that the passive transfer model
      could be used as a diagnostic test in the future.

PMID- 17011823
TI  - Electroencephalogram characteristics of autonomic arousals during sleep in
      healthy men.
AB  - OBJECTIVE: Many sleep disorders involve frequent, brief arousals, not appreciated
      during conventional sleep stage scoring due to lack of electroencephalogram (EEG)
      desynchronization. We evaluated the temporal relation between heart rate (HR)
      changes, an index of autonomic activation, and EEG in seven healthy subjects
      during sleep. METHODS: We identified bouts of tachycardia-bradycardia and
      performed spectral analysis of EEG during these. We also identified cortical
      arousals by the appearance of EEG alpha activity. This allowed us to dichotomize
      bouts of tachycardia-bradycardia by presence or absence of cortical arousal.
      RESULTS: During non-rapid eye movement (REM) sleep, bouts with or without
      cortical arousal occurred with approximately equal frequency. Those with cortical
      arousals usually preceded onset of EEG changes. Those without cortical arousals
      were followed by increases in delta but not alpha power. EEG did not change
      during bouts in REM sleep. CONCLUSIONS: Capturing bouts of tachycardia
      bradycardia is relatively easy via computerized algorithm. Bouts occur with
      cortical arousal or with slow wave synchronization suggestive of subcortical
      arousal. Thus, changes in HR may be useful index of arousal. SIGNIFICANCE: These
      brief bursts of tachycardia-bradycardia are consistent with autonomic arousal.
      Such a measure may be among the first in a continuum of arousal ending with frank
      awakening.

PMID- 17011825
TI  - Evidence of recurrent gene fusions in common epithelial tumors.
AB  - Chromosomal aberrations that accompany carcinogenesis have been documented for
      almost half a century, with gene fusions being the most prevalent type of
      aberration. Gene fusions leading to generation of aberrant fusion proteins or
      aberrant expression of normal proteins are a potent route to carcinogenesis and
      have recently emerged as attractive therapeutic targets. Intriguingly, although
      gene fusions have been widely observed in hematological malignancies, they have
      been far less frequently described in the more-common epithelial carcinomas. It
      has been recently proposed that technical issues, rather than any fundamental
      dichotomy between hematological and solid cancers, account for the under
      representation of gene fusions in epithelial cancers. Recent reports from our
      group support this contention and provide evidence of widespread recurrent gene
      fusions in prostate cancer using a novel analysis of gene-expression profiles.
      Here, we provide an appraisal of the state of the knowledge of gene fusions in
      epithelial cancers. Future implications of gene fusions in common epithelial
      cancers are also discussed.

PMID- 17011824
TI  - Potential of ghrelin as a therapeutic approach for gastrointestinal motility
      disorders.
AB  - Ghrelin was first discovered as a peptide involved in growth hormone release, but
      has now emerged as a new player in the regulation of gastrointestinal function.
      Ghrelin is structurally and functionally related to motilin. Like motilin, it
      induces a specific motor pattern in the fasted state and acts postprandially to
      accelerate gastric emptying. There is no apparent cross-reactivity with motilin
      at the receptor level. Ghrelin agonists have the same potential as motilin
      agonists, and applications in post-operative ileus and gastroparesis have already
      been explored. Although promising, there is still the need to avoid side effects
      and the problems encountered with motilides. This will require drugs with an
      appropriate pharmacokinetic profile. In addition, the dosage regimen and target
      population should be carefully taken into consideration when planning clinical
      trials.

PMID- 17011826
TI  - New therapies for asthma.
AB  - Asthma is an increasing global health problem, and many patients continue to
      suffer from chronic symptoms. However, current therapy with inhaled
      corticosteroids and a long-acting inhaled beta(2)-agonist is highly effective,
      safe and inexpensive. This poses a major hurdle to the development of new
      therapies that aim to improve on current treatments. An important unmet need is
      the treatment of severe asthma, which has different characteristics to mild and
      moderate asthma and is more similar to chronic obstructive pulmonary disease.
      Several new treatments are now under development but many of them are too
      specific, targeting a single receptor, enzyme or mediator, and are unlikely to
      have a major clinical impact. Another unmet need is the development of an
      effective oral therapy for mild and moderate asthma, but it is unlikely that such
      a treatment will be discovered because side effects might be a major problem.
      Prospects for a cure are currently remote but might arise from the development of
      vaccines that target the aberrant immune function in asthma.

PMID- 17011827
TI  - Specificity and efficacy of dendritic cell-based vaccination against tuberculosis
      with complex mycobacterial antigens in a mouse model.
AB  - Dendritic cells (DC) likely play important and unique roles in the generation of
      protective immunity to mycobacteria. In order to clarify their contributions,
      bone marrow-derived DC loaded with Mycobacterium tuberculosis sonicate antigens
      were used to stimulate T cell proliferation both in vitro and in vivo and to
      vaccinate C57BL/6 mice against subsequent challenge with virulent mycobacteria.
      Antigen-pulsed DC developed in fetal calf serum (FCS-DC), but not DC developed in
      normal mouse serum (NMS-DC), stimulated significant proliferation of both naive
      and immune T cells in vitro. The difference between cell populations developed in
      FCS and NMS in the content of CD11c(+) cells and in production of key cytokines
      indicated that NMS is less supportive for the development of activated DC.
      However, following adoptive transfer of a single dose of antigen-pulsed DC into
      naive recipients, NMS-DC induced T cells that proliferated in response to
      mycobacterial antigen, whereas FCS-DC stimulated strong non-specific
      proliferation. Vaccination with two doses of antigen-pulsed NMS-DC by the
      subcutaneous route induced significant protection against intravenous challenge
      with a moderate dose of virulent M. tuberculosis. DC-vaccinated mice exhibited
      significant reductions in bacillary loads in the lungs and spleens, and markedly
      reduced lung pathology. Three doses of antigen-pulsed NMS-DC induced a
      significant increase in survival time following high dose challenge, which
      correlated with a significant increase in IFN-gamma-producing cells in both lung
      and lymphoid tissues, as assessed by the ELISPOT assay. Taken together, these
      results indicate that DC play a critical role in the induction of protective
      resistance against virulent mycobacterial challenge accompanied by the
      development of antigen-reactive, IFN-gamma-producing T cells, and that their
      antigenic specificity is influenced by the culture conditions under which the DC
      are developed.

PMID- 17011828
TI  - Coronary artery wall enhances with intracoronary injection of echocontrast media
      during in vivo intravascular ultrasound.
AB  - Currently, vascularity of the coronary artery wall can be assessed only in vitro.
      We sought to determine if there is any contrast enhancement of the coronary
      artery wall after injection of echocontrast media during in vivo intravascular
      ultrasound imaging, which may represent blood flow within the wall supplied by
      the vasa vasorum.

PMID- 17011829
TI  - Analysis of myocardial perfusion or myocardial function for detection of regional
      myocardial abnormalities. An echocardiographic multicenter comparison study using
      myocardial contrast echocardiography and 2D echocardiography.
AB  - BACKGROUND: Echocardiography based myocardial perfusion imaging and regional wall
      motion analysis are used for evaluation of coronary artery disease and regional
      myocardial abnormalities. AIM: This study sought to compare myocardial contrast
      echocardiography (MCE) and 2D echocardiography with regard to interobserver
      variability and detection of regional myocardial abnormalities. METHODS: In 70
      patients evenly distributed between three ejection fraction groups based on
      biplane cineventriculography ( > 55%, 35-55%, < 35%), unenhanced and contrast
      enhanced 2D echocardiography and myocardial contrast echocardiography (MCE;
      SonoVue; Bracco) were performed. Regional wall motion and myocardial perfusion
      were assessed referring to a 16 segment model. Interobserver agreement (IOA)
      among 2 readers was determined within each imaging modality. To define a standard
      of truth for the presence of segmental myocardial disease an independent expert
      panel decision was obtained based on clinical data, ECG, coronary angiography and
      blinded information from the imaging modalities. RESULTS: Regional wall motion
      assessment was possible in 98.1% of segments using contrast enhanced 2D
      echocardiography and in 87.2% using unenhanced 2D echocardiography (p < 0.001),
      while perfusion assessment was possible in 90.1% of segments (p < 0.001). IOA on
      presence of any regional wall motion abnormality expressed as Kappa coefficient
      was 0.71 (95% CI 0.53-0.89) for contrast enhanced echocardiography and 0.37 (95%
      CI 0.14-0.59) for unenhanced echocardiography. IOA on presence of any perfusion
      abnormality was 0.53 (95% CI 0.34-0.73). For MCE there was high IOA for the
      apical segments (kappa = 0.57) and lower IOA for the basal segments (kappa=0.14),
      while no such gradient was found for the IOA on wall motion abnormalities. Mean
      accuracy to detect expert-panel defined myocardial abnormalities was 80.6% for
      unenhanced echocardiography, 85.0% for contrast enhanced 2D echocardiography and
      80.6% for MCE. CONCLUSIONS: MCE is inferior to contrast enhanced 2D
      echocardiography with regard to visibility of all LV segments and appears
      slightly inferior with regards to IOA, while both are superior to unenhanced 2D
      echocardiography. The methods demonstrated high accuracy in detection of panel
      defined regional myocardial abnormalities.

PMID- 17011830
TI  - Value of contrast echocardiography for the diagnosis of hepatopulmonary syndrome.
AB  - The hepatopulmonary syndrome must be suspected in patients with end-stage liver
      disease and refractory hypoxemia. We report a case of a 49-year-old woman with
      hypoxemia and cirrhosis referred to the cardiac ultrasound laboratory in the
      evaluation of liver transplantation. Contrast-enhanced echocardiography with
      intravenous injection of agitated saline solution was crucial to obtain the
      definitive diagnosis. This imaging modality has proven to be a valuable tool in
      detecting intrapulmonary right-to-left shunt. The present case emphasizes the
      usefulness of contrast echocardiography in the diagnosis of a noncardiac disease
      with important prognosis implications.

PMID- 17011831
TI  - Streptomycin action to the mammalian inner ear vestibular organs: comparison
      between pigmented guinea pigs and rats.
AB  - Streptomycin is the antibiotic of choice to treat tuberculosis and other
      infectious diseases but it causes vestibular malfunction and hipoacusia. Rodents
      are usually employed as models of drug action to the inner ear and results are
      extrapolated to what happens in humans. In rats, streptomycin destroys macular
      sensory cells and does not affect cochlear ones, whereas in guinea pigs the
      contrary is true. Action on the vestibular cristae cells involved in vestibulo
      ocular reflex integrity is less clear. Thus, we compared this response in both
      pigmented guinea pigs (Cavia cobaya) and rats (Rattus norvegicus) after parallel
      streptomycin chronic treatment. In guinea pigs, the reflex was obliterated along
      treatment time; in rats this behavior was not observed, suggesting that the end
      organ target was diverse. In recent studies, streptidine, a streptomycin
      derivative found in the blood of humans and rats treated with streptomycin, was
      the actual ototoxic agent. The putative streptomycin vestibular organ target
      observed in humans corresponds with the guinea pig observations. Results observed
      in rats are controversial: streptidine did not cause any damage either to
      vestibular cristae nor auditory cells. We hypothesize differential drug
      metabolism and distribution and conclude that results in laboratory animals may
      not always be applicable in the human situation.

PMID- 17011832
TI  - Regulation of CDKN2A/B and Retinoblastoma genes in Xiphophorus melanoma.
AB  - Xiphophorus interspecies hybrids provide several well-characterized genetic
      models of melanoma susceptibility. The Xiphophorus CDKN2A/B gene, homologous to
      mammalian CDKN2A/B cyclin-dependent kinase inhibitors (p16 and p15), is a
      candidate tumor susceptibility gene in these models. Using real-time PCR and
      Western blot analysis, we analyzed expression of CDKN2A/B in spontaneous and UV
      induced primary melanomas from individual backcross hybrid fish. We found that
      CDKN2A/B mRNA is highly expressed in melanomas (18-fold), relative to other fish
      tissues. Expression is also elevated, to a lesser extent (9.5-fold), in melanized
      skin from tumor-bearing fish. However, quantitative levels of CDKN2A/B mRNA in
      tumors varied considerably and positively correlated with expression of the Xmrk
      oncogene, suggesting possible functional interaction between Xmrk and CDKN2A/B
      expression. As a homolog corresponding to members of the mammalian CDKN2 family
      which regulate cell cycle progression at the G1 checkpoint, the CDKN2A/B p13
      protein is a putative regulator of the G1 checkpoint apparatus in Xiphophorus.
      Since CDKN2A is often observed to be inversely regulated compared to RB in some
      human tumors, and is capable of transcriptionally regulating RB in human ovarian
      tumors, we cloned the Xiphophorus maculatus RB cDNA and analyzed RB expression by
      real-time PCR and Western blot analysis in the fish melanomas. These experiments
      were designed to ascertain whether CDKN2A/B and RB expression were inversely
      correlated. Our results indicate that RB mRNA was consistently expressed at only
      a 2-fold higher level in both tumors and melanized skin than in muscle.
      Qualitatively similar results were obtained for protein expression. These results
      collectively suggest that (i) Xmrk and CDKN2A/B may be co-regulated at the
      transcriptional level, and (ii) there is little, if any, alteration of RB
      expression in Xiphophorus melanomas.

PMID- 17011833
TI  - Enrichment of OBO ontologies.
AB  - This paper describes a frame-based integration of the three GO subontologies, the
      Chemical Entities of Biological Interest ontology, and the Cell Type Ontology in
      which relationships are modeled in a way that better captures the semantics
      between biological concepts represented by the terms, rather than between the
      terms themselves, than previous frame-based efforts. We also describe a
      methodology for creating suggested enriching assertions by identifying patterns
      in GO terms, mapping these patterns to new, specific relationships, and matching
      term substrings to concepts. Using this methodology, a predicted assertion was
      made for 62% of GO terms that matched one of 31 patterns, and 97% of these
      predicted assertions were assessed to be valid, resulting in an initial set of
      over 4000 assertions. Furthermore, this methodology programmatically integrates
      assertions into an ontology such that each assertion is fully consistent with
      respect to higher (i.e., more general) relevant class and slot levels.

PMID- 17011834
TI  - Early markers of cardiovascular disease.
AB  - Vascular endothelium function plays a pivotal role in cardiovascular pre-clinical
      markers. Nitric oxide secreted by the vascular endothelium has a vasodilatory
      effect that reduces blood pressure which, in turn, prevents increases of left
      ventricular mass and intima-media thickness and improves left ventricular
      relaxation. Modern ultrasound technique allows noninvasive assessment of
      endothelial function and permits identification of functional alteration prior to
      manifestation of anatomical changes in the cardiovascular system. However, effort
      is needed to improve the reliability and reproducibility of ultrasound derived
      measure of endothelial function. This article provides an overview of challenges
      of clinical determination of endothelium-dependent arterial dilatation. In
      addition, we highlight the necessity of targeting the pediatric population in
      studies aimed at preventing and treating cardiovascular disease.

PMID- 17011835
TI  - The effect of omitted covariates on confidence interval and study power in binary
      outcome analysis: a simulation study.
AB  - BACKGROUND/OBJECTIVES: The consequence of omitted but balanced covariates on odds
      ratio point estimation is well-known in the literature. When exposure or
      intervention has a non-null effect on disease outcome, omitted covariates lead to
      underestimation of the effect of exposure or intervention. However, the effect of
      omitted covariates on confidence interval and study power is unknown. STUDY
      DESIGN AND SETTING: A simulation study is carried out to assess the effect of
      omitted covariates on confidence interval and study power for a plausible range
      of scenarios. Coverage probability and study power are assessed systematically
      over a range of study size, type of omitted covariate and magnitude of effect. A
      real-life example using a randomised experiment on flies' sexuality is provided.
      RESULTS: When a balanced covariate is omitted, coverage probability was lowered
      by 2.9-80%. Likewise study power was reduced by as much as 58%. The impact
      becomes substantial when the covariate is continuous, has large variability and
      has a larger effect than the effect of exposure or intervention. The result from
      a real-life example concurs with the simulation finding. CONCLUSION: Omitting an
      important balanced covariate lowers both coverage probability and study power.
      This implies the need for thoughtful consideration of important covariates at the
      design as well as the analysis stages of a study.

PMID- 17011836
TI  - Electrical wiring of Pseudomonas putida and Pseudomonas fluorescens with osmium
      redox polymers.
AB  - Two different flexible osmium redox polymers; poly(1-vinylimidazole)12-[Os-(4,4'
      dimethyl-2,2'-di'pyridyl)2Cl2](2+/+) (osmium redox polymer I) and
      poly(vinylpyridine)-[Os-(N,N'-methylated-2,2'-biimidazole)3](2+/3+) (osmium redox
      polymer II) were investigated for their ability to efficiently "wire" Pseudomonas
      putida ATCC 126633 and Pseudomonas fluorescens (P. putida DSM 6521), which are
      well-known phenol degrading organisms, when entrapped onto cysteamine modified
      gold electrodes. The two Os-polymers differ in redox potential and the length of
      the side chains, where the Os(2+/3+)-functionalities are located. The bacterial
      cells were adapted to grow in the presence of phenol as the sole source of
      organic carbon. The performance of the redox polymers as mediators was
      investigated for making microbial sensors. The analytical characteristics of the
      microbial sensors were evaluated for determination of catechol, phenol and
      glucose as substrates in both batch analysis and flow analysis mode.

PMID- 17011838
TI  - QRAR models for cardiovascular system drugs using biopartitioning micellar
      chromatography.
AB  - The capability of biopartitioning micellar chromatography (BMC) to describe and
      estimate pharmacological parameters of cardiovascular system drugs has been
      studied. The retention of cardiovascular system drugs was studied using different
      pH of Brij-35 as micellar mobile phase in modified C(18) stationary phase.
      Quantitative retention-activity relationships (QRAR) in BMC were investigated for
      these compounds. An adequate correlation between the retention factors (log k)
      and the toxicity (LD(50)) of cardiovascular system drugs was obtained.

PMID- 17011837
TI  - Localization of superoxide anion production to mitochondrial electron transport
      chain in 3-NPA-treated cells.
AB  - 3-Nitropropionic acid (3-NPA), an inhibitor of succinate dehydrogenase (SDH) at
      complex II of the mitochondrial electron transport chain induces cellular energy
      deficit and oxidative stress-related neurotoxicity. In the present study, we
      identified the site of reactive oxygen species production in mitochondria. 3-NPA
      increased O2- generation in mitochondria respiring on the complex I substrates
      pyruvate+malate, an effect fully inhibited by rotenone. Antimycin A increased O2-
      production in the presence of complex I and/or II substrates. Addition of 3-NPA
      markedly increased antimycin A-induced O2- production by mitochondria incubated
      with complex I substrates, but 3-NPA inhibited O2- formation driven with the
      complex II substrate succinate. At 0.6 microM, myxothiazol inhibits complex III,
      but only partially decreases complex I activity, and allowed 3-NPA-induced O2-
      formation; however, at 40 microM myxothiazol (which completely inhibits both
      complexes I and III) eliminated O2- production from mitochondria respiring via
      complex I substrates. These results indicate that in the presence of 3-NPA,
      mitochondria generate O2- from a site between the ubiquinol pool and the 3-NPA
      block in the respiratory complex II.

PMID- 17011839
TI  - Analysis of creatinine in mouse and rat serum by ion exchange high performance
      liquid chromatography for in vivo studies of renal function.
AB  - An ion exchange high performance liquid chromatography method was developed for
      determining creatinine levels in both mouse and rat serum samples. Separation of
      creatinine from other serum components was achieved in 10 min using a 100 x 4.1
      mm, 10 microm strong cation exchange column following acetonitrile precipitation
      of serum proteins. Incorporation of a guard cartridge placed in-line prior to the
      analytical column was employed to prevent interference from compounds used in
      renal disease animal trials. Creatinine levels in normal and diseased animals
      were accurately determined in the 0.01-10 mg/dL range, and average recovery of
      the method was approximately 85% for both mouse and rat serum. Addition of 0.5
      1.0% acetic acid to the acetonitrile used for protein precipitation significantly
      improved creatinine recovery to above 97% in mouse serum. The method was used for
      routine preclinical diagnosis of rat and mouse model renal function, and for the
      evaluation of renal disease treatment efficacy.

PMID- 17011840
TI  - Identification of flavonols in leaves of Maytenus ilicifolia and M. aquifolium
      (Celastraceae) by LC/UV/MS analysis.
AB  - A comparative analysis of the flavonoid components of the leaves of two medicinal
      plants known in Brazil as "espinheira santa", namely, Maytenus ilicifolia Mart.
      ex Reiss. and M. aquifolium Mart. (Celastraceae), and a hybrid plant, M.
      aquifoliumxM. ilicifolia, has been carried out using high-performance liquid
      chromatography coupled with photodiode array UV detection and mass spectrometry.
      One methoxyflavonoid glycoside and 18 flavonol-3-O-glycosides were identified in
      the extracts on the basis of their on-line UV spectra (measured in the absence
      and presence of shift reagents) and multiple stage mass spectral data.
      Fingerprint analysis of the flavonoid extracts revealed significant differences
      in the profiles of the two Maytenus species, while the hybrid plant contained
      flavonoids found in both parent species.

PMID- 17011841
TI  - The frequency of occurrence and discriminatory power of compounds found in human
      scent across a population determined by SPME-GC/MS.
AB  - The composition of human scent collected from the hands is of interest to the
      medical community as a mechanism to diagnose disease and the forensic community
      as a means to investigate canine scent discriminations. An extensive survey of
      the volatile organic compounds (VOCs) identified in the headspace of hand odor
      samples utilizing solid phase micro-extraction gas chromatography/mass
      spectrometry (SPME-GC/MS) has been conducted to determine the constituents of the
      human base odor profile. Sixty-three compounds were extracted from the collected
      odor samples. The composition included acids, alcohols, aldehydes, hydrocarbons,
      esters, ketones and nitrogen-containing compounds. The majority of the compounds
      detected (79.4%) were present in less than one third of the individuals sampled.
      Spearman correlation coefficient comparisons at a match/no-match threshold of 0.9
      produced a distinguish ability of 99.67% across the population.

PMID- 17011842
TI  - Changes in visual acuity in a population over a 15-year period: the Beaver Dam
      Eye Study.
AB  - PURPOSE: To describe the change in visual acuity in a 15-year period. DESIGN:
      Population-based study. METHODS: setting: Beaver Dam, Wisconsin. participants:
      4068 persons 43 to 86 years of age at the time of a baseline examination in 1988
      to 1990, and with follow-up examinations every five years thereafter. observation
      procedures: Best-corrected visual acuity after refraction, assessed by a
      modification of the ETDRS protocol. main outcome measure: Doubling of the visual
      angle; incidence of visual impairment. RESULTS: Eight percent of the population
      developed impaired vision (20/40 or worse), 0.8% developed severe visual
      impairment (20/200 or worse), 7% had doubling of the visual angle, and 2% had
      improved vision. People 75 years of age or older at baseline were more likely to
      develop impaired vision (odds ratio [OR] 12.8, 95% confidence interval [CI] 9.6
      to 17.1, P < .001), doubling of the visual angle (OR 7.8, 95% CI 5.6 to 10.7, P <
      .001), and severe visual impairment (OR 20.6, 95% CI 9.5 to 44.8, P<0.001)
      compared with people younger than 75 years of age. CONCLUSIONS: These data
      provide population-based estimates of the cumulative 15-year incidence of loss of
      vision over a wide spectrum of ages. In people 75 years of age or older the
      cumulative incidence of visual impairment accounting for the competing risk of
      death is 25%, of which 4% is severe, indicating a public health problem of
      considerable proportions as the US population in this age is expected to increase
      by 55% from 18 million in the year 2005 to 28 million by the year 2025.

PMID- 17011843
TI  - Effect of topical prednisolone and diclofenac on the short-term change in
      morphology of posterior capsular opacification.
AB  - PURPOSE: To observe and document the effect of steroidal and nonsteroidal
      antiinflammatory treatment on the formation of Elschnig pearls. DESIGN: A
      prospective, randomized, double blinded, placebo controlled, two-way-cross-over
      study. METHODS: Thirty-nine eyes of 32 patients with pronounced, regeneratory
      posterior capsule opacification (PCO) were included. The patients were treated
      topically with prednisolone and diclofenac (verum) or with lubricating eye drops
      (placebo) four times daily for one week. After a wash-out period of two weeks the
      patients received the contrary treatment also four times daily for one week.
      Digital retroillumination images were taken at day one, three, five, eight, and
      15 of each medication period. The changes in the size of 4,675 Elschnig pearls
      were analyzed. RESULTS: The mean cumulative area of all marked pearls/eye and
      follow-up was 1.2 mm(2) (range: 0.1 mm(2) to 3.2 mm(2)). The mean pearl size was
      12,809 microm(2) (range: 60 microm(2) to 1.08 x 10(6) microm(2)). Between the
      follow-up examinations, 1,274 pearls disappeared (mean: 33 pearls/eye, range:
      five to 69 pearls; 27%) and 777 newly formed pearls appeared (mean: 20
      pearls/eye, range: three to 53 pearls; 20%). There was no statistically
      significant difference in pearl size change and in number of disappeared and
      newly appeared pearls between the verum and the placebo treatments. CONCLUSIONS:
      Topical prednisolone and diclofenac do not influence the short-term change of
      Elschnig pearls. Elschnig pearls disappear and appear within days. The degree of
      progression and regression varies greatly among eyes.

PMID- 17011844
TI  - Evaluation of lens epithelial cell migration in vivo at the haptic-optic junction
      of a one-piece hydrophobic acrylic intraocular lens.
AB  - PURPOSE: To evaluate the pattern of lens epithelial cell (LEC) ingrowth behind
      the intraocular lens (IOL) optic in patients implanted with the AcrySof SA60AT
      one-piece IOL. DESIGN: Retrospective case series. METHODS: Patients implanted
      with the AcrySof SA60AT one-piece IOL with complete overlap of the capsulorrhexis
      and IOL optic and no ocular pathology were selected from the practices of six
      surgeons. High-resolution digital images of the distribution of LECs were
      captured. Circumferential location and extent of LEC growth behind the optic were
      measured. RESULTS: Mean +/- SD follow-up was 13.2 +/- 1.7 months for 40 patients
      (mean age 72 years). LEC migration beyond the edge of the IOL optic was displayed
      by 57.5% (23/40) of patients. LECs migrated into the visual axis in 22.5% (9/40)
      of patients, leading to a visual acuity of <6/9 (20/30) in 10% (4/40) of
      patients. Cell migration was located preferentially at the optic-haptic junction.
      Serial photographs were used to monitor LEC migration over time. In some cases,
      LECs extended from the opposing optic-haptic junctions to converge in the center
      of the IOL, creating a path across the optic. CONCLUSIONS: The optic-haptic
      junction of the AcrySof one-piece IOL is a point of weakness in the barrier
      effect of the square-edge IOL design that provides migrating LECs access to the
      posterior capsule.

PMID- 17011845
TI  - Efficacy of oral antiviral prophylaxis in preventing ocular herpes simplex virus
      recurrences in patients with and without self-reported atopy.
AB  - PURPOSE: To compare the efficacy of oral antiviral prophylactic treatment for
      herpes simplex virus (HSV) recurrences in patients with and without self-reported
      atopy. DESIGN: Retrospective cohort comparative study. METHODS: setting: Cornea
      Service, Wills Eye Hospital. study population: Patients who presented with
      previously diagnosed ocular HSV between March 2003 and March 2004. From 244
      patients invited, 54 patients (58 eyes) were included. One hundred and ninety
      patients were excluded according to exclusion criteria: no active episode during
      follow-up, immunosuppression, less than one year of follow-up, or previous
      history of penetrating keratoplasty. The Questionnaire regarding history of
      atopic disease, considers: presence of allergic rhinitis, asthma or atopic
      dermatitis, and chart review of ocular history. main outcome measures: Incidence
      of all types of HSV recurrences with and without antiviral prophylaxis within
      each group and between groups. HSV episodes were classified into infectious,
      inflammatory, and mixed for analysis. RESULTS: Atopic/nonatopic (P value): mean
      follow-up without prophylaxis 8.1 (+/- 8.2)/7.3 years (+/- 8.6) (P = .71); mean
      follow-up with prophylaxis 2.9 (+/- 2.3)/2.6 years (+/- 2.2) (P = .51); the
      effect of prophylaxis significantly reduced the all recurrences in both groups
      except in the inflammatory recurrences in the atopic group and in the mixed
      recurrences in both groups. Prophylaxis decreased infectious episodes by 44% in
      nonatopic and 76% in atopics and decreased inflammatory manifestations by 69% in
      the nonatopic group and 8% in the atopic group. CONCLUSION: Antiviral prophylaxis
      for HSV recurrences was more effective in reducing infections in atopics and less
      effective in reducing inflammatory episodes in atopics versus nonatopics.

PMID- 17011846
TI  - Topical interferon alfa-2b for the treatment of recalcitrant ocular surface
      squamous neoplasia.
AB  - PURPOSE: To evaluate topical interferon alfa-2b (IFN-alpha2b) for the treatment
      of recalcitrant ocular surface squamous neoplasia (OSSN). DESIGN: Prospective,
      noncomparative, interventional consecutive case series. METHODS: Ten patients
      with recalcitrant OSSN were treated with topical IFN-alpha2b (1 million IU/ml)
      four times a day until clinical resolution of the lesion or until the lesion
      appeared nonresponsive-that is, treatment failure. Progress was assessed by
      clinical examination and photographic records, with a minimum follow-up of six
      months. RESULTS: Eight of 10 patients achieved clinical resolution from topical
      IFN-alpha2b treatment. One patient developed invasive squamous cell carcinoma and
      underwent exenteration. The other patient required further mitomycin C therapy to
      achieve clinical resolution. The mean duration to clinical resolution for the
      eight patients treated with IFN-alpha2b was 21.9 weeks (range six to 59 weeks).
      There have been no recurrences for any of the nine patients during follow-up
      (mean 55.0 weeks; range 26 to 84 weeks). CONCLUSIONS: Topical IFN-alpha2b is an
      important treatment modality for recalcitrant OSSN; it avoids the risks of
      further limbal stem cell destruction from other agents and surgical excision. If
      invasive disease is diagnosed at any stage, topical therapy is contraindicated,
      necessitating surgical excision.

PMID- 17011847
TI  - Optimization of anterior eye fluorescein viewing.
AB  - PURPOSE: To optimize anterior eye fluorescein viewing and image capture. DESIGN:
      Prospective experimental investigation. METHODS: The spectral radiance of ten
      different models of slit-lamp blue luminance and the spectral transmission of
      three barrier filters were measured. Optimal clinical instillation of fluorescein
      was evaluated by a comparison of four different instillation methods of
      fluorescein into 10 subjects. Two methods used a floret, and two used minims of
      different concentration. The resulting fluorescence was evaluated for quenching
      effects and efficiency over time. RESULTS: Spectral radiance of the blue
      illumination typically had an average peak at 460 nm. Comparison between three
      slit-lamps of the same model showed a similar spectral radiance distribution. Of
      the slit-lamps examined, 8.3% to 50.6% of the illumination output was optimized
      for >80% fluorescein excitation, and 1.2% to 23.5% of the illumination overlapped
      with that emitted by the fluorophore. The barrier filters had an average cut-off
      at 510 to 520 nm. Quenching was observed for all methods of fluorescein
      instillation. The moistened floret and the 1% minim reached a useful level of
      fluorescence in on average approximately 20s ( approximately 2.5x faster than the
      saturated floret and 2% minim) and this lasted for approximately 160 seconds.
      CONCLUSIONS: Most slit-lamps' blue light and yellow barrier filters are not
      optimal for fluorescein viewing and capture. Instillation of fluorescein using a
      moistened floret or 1% minim seems most clinically appropriate as lower
      quantities and concentrations of fluorescein improve the efficiency of clinical
      examination.

PMID- 17011848
TI  - Baseline optical coherence tomography predicts the development of glaucomatous
      change in glaucoma suspects.
AB  - PURPOSE: To assess whether baseline retinal nerve fiber layer (RNFL) measurements
      obtained with optical coherence tomography (OCT2; Carl Zeiss Meditec, Dublin,
      California, USA) are predictive of the development of glaucomatous change.
      DESIGN: Cohort study. METHODS: Participants were recruited from the University of
      California, San Diego (UCSD) longitudinal Diagnostic Innovations in Glaucoma
      Study (DIGS). One eye was studied from each of 114 glaucoma suspects with normal
      standard automated perimetry (SAP) and OCT RNFL imaging at baseline. The cohort
      was divided into two groups based on the development of glaucomatous change
      (repeatable abnormal visual fields and/or a change in the stereophotographic
      appearance of the optic disk). Cox proportional hazards models were used to
      determine the predictive ability of OCT RNFL thickness measurements. RESULTS:
      Over a 4.2-year average follow-up period, 23 eyes (20%) developed glaucomatous
      changes and 91 (80%) did not. At baseline, thinner RNFL measurements, higher SAP
      pattern standard deviation (PSD), "glaucoma" stereophotograph assessment, and
      thinner central corneal thickness (CCT) were associated with the study endpoints
      in univariate analysis. After adjusting for age, intraocular pressure (IOP), CCT,
      and PSD in multivariate models, a 10 mum thinner average, superior and inferior
      RNFL at baseline was predictive of glaucomatous change [hazard ratio (95% CI);
      1.51 (1.11 to 2.12), 1.57 (1.17 to 2.18), and 1.49, (1.19 to 1.91),
      respectively]. Results were consistent when stereophotographic assessment was
      included in multivariate analysis. CONCLUSIONS: Thinner OCT RNFL measurements at
      baseline were associated with development of glaucomatous change in glaucoma
      suspect eyes. RNFL thinning was an independent predictor of the glaucomatous
      change, even when adjusting for stereophotograph assessment, age, IOP, CCT, and
      PSD.

PMID- 17011849
TI  - Comparison of dynamic contour tonometry and goldmann applanation tonometry in
      glaucoma patients and healthy subjects.
AB  - PURPOSE: To investigate the agreement in the measurement of intraocular pressure
      (IOP) obtained by dynamic contour tonometry PASCAL (DCT-PASCAL) and Goldmann
      applanation tonometry (GAT) in glaucoma eyes and healthy eyes with different
      central corneal thickness (CCT). DESIGN: Prospective cross-sectional study.
      METHODS: In a randomized order, three consecutive IOP measurements were performed
      on 197 eyes of 107 subjects by one examiner using both DCT-PASCAL and GAT on all
      eyes. Furthermore, ultrasonic pachymetry was performed. The Spearman correlation
      coefficient (r) was determined to compare IOP readings between DCT-PASCAL and
      GAT. Regression-based Bland and Altman analysis was used to evaluate agreement
      between the instruments. RESULTS: Mean IOP values obtained by both instruments
      were significantly correlated in healthy and glaucoma eyes (all healthy eyes [n =
      66]: r = 0.8, P < .001, all glaucoma eyes [n = 131]: r = 0.96, P < .001). Neither
      GAT nor DCT-PASCAL showed a significant correlation with CCT (GAT: all eyes: r =
      0.009, P = .9, DCT-PASCAL: all eyes: r = -0.05, P = .5). Bland and Altman
      analysis revealed the existence of proportional bias. Thus, 95% limits of
      agreement between the instruments varied with the actual IOP measurement.
      CONCLUSIONS: DCT-PASCAL and GAT revealed a strong correlation in IOP measurements
      between glaucoma and healthy eyes. However, the analysis of agreement indicated
      some discrepancies between the instruments. Measurements with both GAT and DCT
      PASCAL were not correlated with central corneal thickness.

PMID- 17011850
TI  - Assessment of axonal degeneration along the human visual pathway using diffusion
      trace analysis.
AB  - PURPOSE: The effectiveness of diffusion trace value analysis for non-invasive
      assessment of retinal ganglion cell (RGC) axonal degeneration at multiple
      anatomic levels along the human visual pathway under clinical setting was
      evaluated. DESIGN: Imaging study. METHODS: Ten patients with unilateral chronic
      optic neuropathy of varying cause and 16 age-matched normal subjects were
      studied. Trace, a tensor invariant that is considered to be a sensitive index for
      pathologic changes in axons, was analyzed at nine anatomic sites in each subject,
      namely, bilaterally at the level of the optic nerves, uncrossed chiasmal fibers,
      optic tracts and optic radiations, and crossed chiasmal fibers, using a 3.0 Tesla
      magnetic resonance imaging system. RESULTS: Trace values of the optic nerve and
      uncrossed chiasmal fibers ipsilateral to the affected eye, the crossed chiasmal
      fibers, and optic tracts bilaterally were significantly higher than those of the
      corresponding anatomic sites in normal subjects. The optic nerve and uncrossed
      chiasmal fibers ipsilateral to the unaffected side and optic radiations,
      bilaterally, had trace values which were not significantly different from the
      values of the corresponding anatomic levels in normal subjects. The increase in
      trace value in the optic nerve and uncrossed chiasmal fibers ipsilateral to the
      affected side was greater than those of the crossed chiasmal fibers and optic
      tracts. CONCLUSIONS: Findings are highly consistent with a degenerative process
      of RGC axons and trace values are quantitatively well correlated to predicted
      pathology at the given anatomical sites. Trace value measurement at multiple
      sites along fiber pathways appears to be a powerful addition to clinical
      assessment of the functionality of components of the visual pathways during
      various stages of a pathologic process.

PMID- 17011851
TI  - Measurement of the actual dose of triamcinolone acetonide delivered by common
      techniques of intravitreal injection.
AB  - PURPOSE: To measure the actual dose of triamcinolone acetonide (TA) delivered
      during intravitreal injection performed by several common techniques. DESIGN:
      Experimental study. METHODS: A 0.1-ml, 40-mg vial of TA (Kenalog-40; Bristol
      Myers-Squibb, Peapack, New Jersey, USA) was prepared according to one of four
      protocols and the mass determined after drying overnight on waxed paper. In group
      1, a 0.1-ml aliquot of TA was dispensed with a 30-gauge needle after shaking the
      vial 10 or 30 times. Group 2 used a 27-gauge needle. In group 3, the supernatant
      was removed from the crystals. Group 4 passed the suspension through a 0.2-microm
      micropore filter and rinsed the crystals with saline. RESULTS: There was no
      statistically significant difference between 30- or 27-gauge needles (P = 0.83, t
      test) or between shaking the vial 10 or 30 times before withdrawing the drug (P =
      0.99). A statistically significant difference (t test, P = 0.001) was found
      between TA delivered from the initial 60% of each syringe (mean +/- SD, 2.7 +/-
      1.0 mg) to that drawn from the last 40% of each syringe (7.8 +/- 3.6 mg). Group 3
      had a mean weight of 32.1 +/- 7.0 mg and group 4, 10.6 +/- 2.1 mg. CONCLUSIONS:
      Efforts to achieve a 4.0-mg dose of TA, regardless of method used, are variable
      and inconsistent. Injecting through a small-gauge needle appears to concentrate
      the remaining suspension. Techniques to concentrate TA or remove aqueous
      preservatives by filtering effectively increase the concentration, but these
      results are variable.

PMID- 17011852
TI  - Polypoidal choroidal vasculopathy with choroidal vascular hyperpermeability.
AB  - PURPOSE: To describe the incidence and clinical characteristics of polypoidal
      choroidal vasculopathy (PCV) associated with choroidal vascular
      hyperpermeability. DESIGN: Retrospective observational case series. METHODS: We
      reviewed the medical records of 122 consecutive eyes with PCV and 106 consecutive
      eyes with exudative age-related macular degeneration (AMD). Fluorescein
      angiography and indocyanine green (ICG) angiography were performed using a
      confocal scanning laser system. In the midphase of ICG angiography, we evaluated
      choroidal vascular hyperpermeability, which is recognized as one of the
      characteristic findings in central serous chorioretinopathy (CSC). Choroidal
      vascular hyperpermeability appeared as multifocal patchy areas of
      hyperfluorescence with blurred margins within the choroid that increased in
      intensity with time after injection of the dye. RESULTS: Of 122 eyes with PCV, 12
      (9.8%) eyes of 10 patients exhibited multifocal choroidal hyperfluorescence in
      the midphase of ICG angiography, whereas two (1.9%) of 106 eyes with exudative
      AMD showed a similar appearance (P = .013). Of the 12 eyes in 10 patients with
      PCV that demonstrated multifocal choroidal hyperfluorescence, we also noted that
      the early phase of ICG angiography showed choroidal filling delay in seven eyes
      (58%) and venous dilation in 12 eyes (100%). Four of these 12 eyes (33%) had a
      medical history of CSC, and nine (90%) of the 10 patients revealed multifocal
      choroidal hyperfluorescence bilaterally. CONCLUSIONS: Multifocal choroidal
      hyperfluorescence seen by ICG angiography occurs more frequently in eyes with PCV
      than in those with AMD. Choroidal vascular hyperpermeability, reportedly a
      characteristic finding in CSC, might be one of the risk factors of PCV.

PMID- 17011853
TI  - Ultrasonographic characteristics and treatment outcomes of surgery for vitreous
      hemorrhage in idiopathic polypoidal choroidal vasculopathy.
AB  - PURPOSE: To describe the ultrasonographic characteristics and treatment outcomes
      of surgery in vitreous hemorrhage (VH) associated with idiopathic polypoidal
      choroidal vasculopathy (IPCV). DESIGN: Retrospective interventional and
      observational case series. METHODS: Clinical, ultrasound, and surgical data of 10
      consecutive patients operated for VH due to IPCV in a tertiary eye institute was
      studied by chart review. Data were analyzed to determine the clinical features,
      ultrasonographic characteristics, and surgical outcomes. An additional five
      patients with IPCV without VH were evaluated by ultrasound in various stages of
      the disease. RESULTS: Between January 1998 and March 2005, 10 eyes of 10 patients
      underwent vitreous surgery for VH associated with IPCV. Characteristic
      ultrasonographic features that helped the diagnosis preoperatively included focal
      choroidal thickening without excavation or acoustic hollowing with associated low
      reflective echoes of dispersed VH, or diffuse choroidal thickening and low
      intensity echoes of dispersed hemorrhage on either side of the retinal spike,
      often without vitreous detachment spike. Oral corticosteroids were provided
      preoperatively to patients with associated exudative retinal detachment.
      Indocyanine green angiography (ICGA) confirmed IPCV postoperatively. Focal
      lesions were treated with laser photocoagulation. Anatomical success was seen in
      nine of 10 eyes. Visual acuity improved in five of 10 eyes but was limited by
      macular pathology in other five eyes. The most common complication was iatrogenic
      tears. Some eyes had recurrent IPCV lesions in follow-up. CONCLUSIONS:
      Characteristic ultrasonographic features could identify IPCV in eyes with VH.
      Anatomical and visual outcomes of our management approach were encouraging and
      need further study.

PMID- 17011854
TI  - Reading performance of patients with uveitis-associated cystoid macular edema.
AB  - PURPOSE: To evaluate the extent of the visual impairment caused by uveitis
      associated cystoid macular edema (CME) and compare the results with lesion size.
      DESIGN: Observational case series. METHODS: setting: Uveitis outpatient clinic of
      the Department of Ophthalmology and Optometry, Medical University of Vienna.
      patient population: CME was verified in 30 eyes of 30 consecutive uveitis
      patients with optical coherence tomography and lesion size was assessed with
      retinal thickness analyzer. main outcome measures: Distance visual acuity (VA)
      (measured with Early Treatment Diabetic Retinopathy Study charts), reading
      acuity, and reading speed (tested with Radner Reading Charts). Results were
      compared with nonaffected partner eyes. RESULTS: Distance VA was logMAR 0.22 +/-
      0.15 in CME eyes vs -0.02 +/- 0.17 in healthy controls. Reading acuity was 75% of
      logMAR in CME eyes vs 92% of logMAR in control eyes (P = .01). The mean reading
      speed was 148.4 +/- 36.6 words per minute in patients with CME vs 168.9 +/- 36.3
      in patients without CME (P = .04). Reading acuity correlated with both lesion
      size and distance VA (r = 0.61; P = .01 and r = 0.53; P = .028, respectively).
      Neither anatomical classification of uveitis nor gender or age had a significant
      influence on the evaluated parameters. CONCLUSIONS: Reading acuity and reading
      speed were considerably more impaired than distance visual acuity. The assessed
      parameters showed a better correlation to lesion size and seem to be a better
      reflection of macular dysfunction. Analyzing reading function is an important
      factor when following patients with CME and evaluating success of treatment
      modalities.

PMID- 17011855
TI  - The expression of cyclooxygenase 2 in retinoblastoma: primary enucleated eyes and
      enucleation after conservative treatment.
AB  - PURPOSE: To provide insight into the relationship between cyclooxygenase-2 (COX
      2) expression and histopathologic features of retinoblastoma specimens treated
      either by primary or secondary enucleation. DESIGN: Laboratory investigation.
      METHODS: Twenty-five retinoblastoma specimens received between 1994 and 2003 were
      retrieved for this study from the Ocular Pathology Registry, Federal University
      of Sao Paulo, Brazil and the Henry C. Witelson Ocular Pathology Laboratory and
      Registry, McGill University, Montreal, Canada. The specimens retrieved were
      divided into two groups: Group I, enucleation was performed as a form of primary
      treatment (n = 15) and Group II, enucleation after failure of conservative
      treatment (n = 10). Patient information and formalin-fixed, paraffin-embedded
      specimens were obtained. New sections of these blocks were used for hematoxylin
      and eosin stain and for immunoassay using a monoclonal mouse anti-COX-2 antibody.
      Two independent ophthalmic pathologists reviewed all of the microslides. RESULTS:
      Twenty-three specimens (92%) presented a high expression of COX-2 (15 in Group I;
      eight in Group II) and there was no statistical difference in COX-2 expression
      between the two groups (P = .07). However, all specimens expressed COX-2 to a
      different degree. The areas of tumor invasion were positive for COX-2 in 87.5% of
      the two groups. CONCLUSION: Most retinoblastoma specimens revealed a high COX-2
      expression. Future studies will be necessary to correlate the high expression of
      COX-2 in retinoblastoma and a possible applicability of anti-COX-2 medications in
      the treatment of these tumors.

PMID- 17011856
TI  - Strabismus surgery for elimination of bifocals in accommodative esotropia.
AB  - PURPOSE: This study reports the outcomes of strabismus surgery to eliminate
      bifocals in patients with accommodative esotropia with a high accommodative
      convergence to accommodation (AC:A) ratio. DESIGN: Retrospective interventional
      case series. METHODS: Sixteen patients who wore bifocals for treatment of
      accommodative esotropia with a high AC:A ratio underwent strabismus surgery
      following prism adaptation testing (PAT) for the near angle of esotropia without
      bifocals. Outcomes were considered successful if patients had microtropias and
      maintained fusion without bifocals. RESULTS: All patients had successful outcomes
      after one or two surgeries. Three of 13 (23%) patients with positive PATs
      required two surgeries. Two of three (67%) patients with negative PATs required
      two surgeries. Binocularity remained the same in 13 patients and improved in
      three patients. Glasses were eliminated entirely in eight of 16 (50%) patients.
      CONCLUSIONS: Strabismus surgery may eliminate the need for bifocal glasses in
      patients with accommodative esotropia with a high AC:A ratio, with many patients
      able to discontinue glasses entirely. Preoperative PAT may help predict the risk
      of requiring more than one surgery.

PMID- 17011857
TI  - Early vitreous surgery for aggressive posterior retinopathy of prematurity.
AB  - PURPOSE: To assess the efficacy of early vitrectomy for aggressive posterior
      retinopathy of prematurity (ROP) to stop progression of retinal detachment.
      DESIGN: Retrospective, noncomparative, consecutive case series. METHODS: Twenty
      two eyes (15 patients) with aggressive posterior ROP underwent vitrectomy with or
      without lens sparing, because retinal photocoagulation failed to stop progression
      of fibrovascular proliferation, despite being performed early, densely, and with
      early retreatment. We assessed the status of retinal attachment and foveal
      formation ophthalmoscopically and the presence or absence of fixation of visual
      behavior. RESULTS: Follow-up ranged from six to 12 months (mean, 9 months). Six
      eyes (100%) in which a lens-sparing vitrectomy was performed developed a large
      tractional retinal detachment. In contrast, the retinas were completely
      reattached in 16 eyes (100%) in which vitrectomy with lensectomy was performed,
      nine eyes (56%) had foveal configuration, and 14 eyes (88%) had steady fixation.
      CONCLUSIONS: These results suggest that early vitrectomy is effective for
      preventing retinal detachment in aggressive posterior ROP.

PMID- 17011858
TI  - Intracranial vascular anomalies in patients with morning glory disk anomaly.
AB  - PURPOSE: An association between morning glory disk anomaly (MGDA) and
      intracranial vascular anomalies including Moyamoya disease has been recognized.
      We evaluated a series of patients with MGDA to ascertain the frequency of
      cerebrovascular anomalies. DESIGN: Retrospective observational case series.
      METHODS: We reviewed the neurologic histories and neuroimaging studies of twenty
      patients with MGDA at two institutions between 1982 and 2004. Magnetic resonance
      imaging (MRI) and magnetic resonance angiography (MRA) of the brain was performed
      on all patients who had not undergone neuroimaging. MRI/MRA studies done for 40
      pediatric patients without MGDA were also evaluated for cerebrovascular
      anomalies. The prevalence of anomalies in the two groups was compared by Fisher
      exact test. RESULTS: Nine of 20 patients (45%) with MGDA had cerebrovascular
      anomalies. Anomalies ranged from agenesis of the A1 segment of the anterior
      cerebral artery to bilateral stenosis of the internal carotid arteries with
      moyamoya disease. Three patients underwent revascularization procedures. Ten of
      40 patients (25%) in the control group had any intracranial vascular anomaly,
      whereas only two of 40 (5%) had an abnormality of the anterior circulation, the
      most common finding in the MGDA group. CONCLUSION: We recommend that all patients
      with MGDA undergo MRI/MRA or computerized tomographic angiography to detect
      vascular and structural brain anomalies. It may be unclear whether
      cerebrovascular anomalies represent isolated congenital anomalies or findings of
      progressive occlusive cerebrovascular disease. Follow-up imaging should be
      considered in patients with cerebrovascular anomalies and is clearly indicated if
      neurologic signs or symptoms are present.

PMID- 17011859
TI  - Pediatric horner syndrome: etiologies and roles of imaging and urine studies to
      detect neuroblastoma and other responsible mass lesions.
AB  - PURPOSE: To evaluate the frequency of etiologies of Horner syndrome in children
      and suggest an imaging and laboratory diagnostic protocol to evaluate for
      neuroblastoma and other lesions in a child presenting with Horner syndrome and no
      known cause. DESIGN: Retrospective chart and data review. METHODS: A
      retrospective review of all children seen at a large pediatric neuro
      ophthalmology referral center with a diagnosis of Horner syndrome between 1993
      and 2005 with particular attention to underlying etiologies and the results of
      imaging and urine catecholamine studies. RESULTS: Fifty-six children met criteria
      for Horner syndrome and further review. Twenty-eight children (50%) had no
      previously identified cause for Horner syndrome. Of these children, 24 (85.7%)
      had urine catecholamine metabolite studies, and all had negative results. Twenty
      (71.4%) had complete modern imaging of the brain, neck, and chest. Of the 18
      children who had complete imaging and urine studies, responsible mass lesions
      were found in six (33%). Four had neuroblastoma, one had Ewing sarcoma, and the
      other had juvenile xanthogranuloma. Of all patients (diagnosis known and
      unknown), neoplasm was the etiology in 13 of 56 (23%) of patients. CONCLUSIONS:
      We confirm that Horner syndrome in a child of any age without a surgical history
      requires a complete examination to exclude a mass lesion. In such patients, we
      recommend brain, neck, and chest magnetic resonance imaging (MRI) with and
      without contrast as well as urinary catecholamine metabolite testing. However,
      imaging is more sensitive than urine testing in this setting.

PMID- 17011860
TI  - Antivascular endothelial growth factor agents and their development: therapeutic
      implications in ocular diseases.
AB  - PURPOSE: To provide an overview of angiogenesis and vascular endothelial growth
      factor (VEGF) and discusses the development approach, safety, and efficacy
      results of current and emerging anti-VEGF therapies for ocular diseases. DESIGN:
      Analysis of literature and current clinical trials of antiangiogenic agents for
      age-related macular degeneration (AMD). METHODS: Literature review. RESULTS:
      There are several novel antiangiogenic molecules that target vascular endothelial
      growth factor and are being used in the management of AMD. Large scale, Phase III
      trials have shown promising results in improving vision in this devastating
      disease. CONCLUSIONS: Therapies that target VEGF have shown tremendous promise as
      treatments for AMD.

PMID- 17011861
TI  - Comparison of corneal sensitivity and tear function following Epi-LASIK or laser
      in situ keratomileusis for myopia.
AB  - PURPOSE: To compare the effect of Epi-LASIK or Laser In Situ Keratomileusis
      (LASIK) on corneal sensitivity and tear function. DESIGN: Prospective, non
      randomized comparative clinical trial. METHODS: Seventy-nine eyes (Group A)
      underwent Epi-LASIK and 61 eyes underwent LASIK (Group B) for the treatment of
      myopia. Matching parameters between the groups were age and attempted correction.
      Corneal sensitivity, tear break-up time (BUT), and Schirmer test II were
      evaluated before and at one, three, and six months after the procedure. RESULTS:
      Corneal sensitivity and BUT were decreased at one month in Group A (P < .001) to
      be restored by the third month (P = .71 and P = .58, respectively). In Group B,
      corneal sensitivity and BUT were reduced postoperatively (P < .001). There was a
      significant difference in corneal sensitivity between the two groups at all
      postoperative intervals. Schirmer test II was not significantly decreased
      postoperatively in Group A. In Group B, it was decreased at one and three months
      and restored by the sixth month. CONCLUSION: Epi-LASIK-treated eyes had faster
      rehabilitation of corneal sensitivity and tear function than LASIK-treated eyes.

PMID- 17011862
TI  - Time to resolution of corneal edema after long-term contact lens wear.
AB  - PURPOSE: To evaluate corneal thickness changes after soft contact lens (SCL)
      removal in laser in situ keratomileusis (LASIK) candidates. DESIGN: Observational
      case series. METHODS: A total of 100 eyes daily wearing SCL for at least six
      months were evaluated. The central corneal thickness (CCT) was measured by
      pachymetry immediately after lens removal and then repeated daily until it became
      stable. RESULTS: CCT immediately after lens removal was 557.4 +/- 32 microm, and
      when edema completely resolved was 521.8 +/- 25 microm. Corneal edema required
      two to 15 days after discontinuation of SCL wear to resolve. Corneal thickness
      stabilized in 74% of patients within the first week and in 26% of patients during
      the second week. Older patients and more primary corneal edema needed longer time
      to recover (P < .0001). CONCLUSION: Discontinuing SCL wear at least 15 days
      before keratorefractive surgery is recommended to achieve accurate pachymetry.

PMID- 17011863
TI  - Topical cyclosporine-a combined with mitomycin C for conjunctival and corneal
      squamous cell carcinoma.
AB  - PURPOSE: To determine the efficiency of topical cyclosporine-A (CSA) combined
      with mitomycin C (MMC) as an adjunctive treatment in diffuse conjunctival and
      corneal squamous cell carcinoma (CCSC). DESIGN: Interventional case reports.
      METHODS: Two patients who had positive margins following surgical excision of
      CCSC were treated by topical CSA (0.05%) four times a day for 12 weeks, and
      topical MMC (0.01%) four times a day was combined with CSA at the second, fourth,
      and sixth weeks of the treatment. We controlled the tumor recurrence, vision, and
      ocular surface healing during the follow-up. RESULTS: There was no tumor
      recurrence during the follow up of 18 months. Limbal vascularization regressed
      considerably and the vision improved without any ocular surface problems in both
      patients. CONCLUSIONS: As an adjunctive treatment, topical CSA (0.05%) combined
      with MMC (0.01%), may prevent tumor recurrence and provide excellent ocular
      surface healing in diffuse CCSC.

PMID- 17011864
TI  - Role of scheimpflug imaging in traumatic intralenticular foreign body.
AB  - PURPOSE: The role of Pentacam Scheimpflug imaging in evaluation of penetrating
      eye injury and intralenticular foreign body (ILFB). DESIGN: Interventional case
      report. METHODS: A 35-year-old male presented to our clinical practice with
      penetrating eye injury and endophthalmitis. Scheimpflug imaging helped localize
      the intralenticular foreign body (ILFB). It confirmed the posterior capsule to be
      intact. He underwent phacoemulsification, foreign body removal, and intraocular
      lens (IOL) implant. Postoperatively, IOL was imaged with Pentacam Scheimpflug
      imaging. RESULTS: Scheimpflug imaging allowed us to confirm the presence and
      exact location of ILFB and its relation to the intact posterior capsule as well
      as the postoperative IOL positioning. This helped in better planning of
      management of traumatic cataract with ILFB. CONCLUSIONS: Pentacam is a potential
      tool for accurate localization of foreign bodies lodged in the lens and provides
      an objective basis for better patient counseling and surgical planning.

PMID- 17011865
TI  - Closure of persistent cyclodialysis cleft using the haptics of the intraocular
      lens.
AB  - PURPOSE: To evaluate a technique for ab-interno repair of cyclodialysis cleft in
      conjunction with placement of an intraocular lens (IOL). DESIGN: Interventional
      case reports. METHODS: setting: Clinical practice. patients: Two eyes of two
      patients, one phakic and one aphakic, present with hypotony secondary to
      traumatic cyclodialysis cleft. intervention: A single piece all-polymethyl
      methacrylate intraocular lens (PMMA IOL) 13.5 mm in diameter was placed in the
      ciliary sulcus with the haptics placed in the area of cyclodialysis cleft during
      cataract surgery and secondary placement of IOL. main outcome measures:
      Intraocular pressure (IOP). RESULTS: Hypotony resolved in both patients on the
      first postoperative day and the IOP was maintained above 10 mm Hg for more then
      36 months postoperatively. CONCLUSIONS: In the setting of hypotony from a
      traumatic cyclodialysis cleft, the haptics of an IOL can be used as an internal
      cerclage during cataract or secondary IOL surgery to effectively close the cleft
      by direct apposition of the ciliary body to the overlying sclera.

PMID- 17011866
TI  - Bacterial culture isolates from hospitalized pediatric patients with
      conjunctivitis.
AB  - PURPOSE: To determine the spectrum of organisms causing acute bacterial
      conjunctivitis in hospitalized children at a tertiary care referral center.
      DESIGN: Retrospective chart review. METHODS: Charts of hospitalized children with
      positive conjunctival cultures were reviewed, and patients with clinical
      description of conjunctivitis were studied. RESULTS: One hundred and seven
      isolates from 59 patients were included in the study. The most common organisms
      cultured were coagulase-negative Staphylococcus (59.3% of patients), viridans
      Streptococcus (47.5%), and Staphylococcus aureus (20.3%). The type of organisms
      differed based on age, with S. aureus and Haemophilus influenzae being more
      common in nonneonates. Gram-negative bacilli and methicillin-resistant
      Staphylococcus species were more common in patients hospitalized longer than two
      days. CONCLUSIONS: The distribution of bacterial organisms causing acute
      bacterial conjunctivitis in our hospitalized children differs from that of
      previous reports in the outpatient setting. Conjunctival swabbing for culture and
      sensitivities before instituting empiric broad-spectrum antibiotic therapy may be
      useful.

PMID- 17011867
TI  - Choroidal ischemia after photodynamic therapy with verteporfin for choroidal
      neovascularization.
AB  - PURPOSE: To report delay in choroidal perfusion suggestive of ischemia after
      photodynamic therapy (PDT) with verteporfin for choroidal neovascularization
      (CNV). DESIGN: Observational case series. METHODS: Retrospective review of all
      patients who developed choroidal ischemia after PDT. RESULTS: This vascular
      change was found in eight (2.1%) of 373 eyes of patients treated for CNV as a
      result of age-related macular degeneration (AMD) and in one (0.9%) of 114 eyes
      treated for pathologic myopia. A decrease of 3 lines of vision was reported to
      occur one week after treatment in patients with AMD. At the 12-month examination,
      patients did not exhibit any marked changes in visual acuity. CONCLUSIONS:
      Choroidal ischemia was an uncommon manifestation owing to the selectivity of
      verteporfin therapy and the existence of abundant anastomotic vascular
      connections in the choroid. The low incidence of this vascular event should not
      preclude counseling PDT in eyes that could benefit greatly from this therapy.

PMID- 17011868
TI  - Progression of choroidal neovascularization following injection of pegaptanib
      sodium (macugen) in two eyes with neovascular age-related macular degeneration.
AB  - PURPOSE: To describe two cases of neovascular age-related macular degeneration
      (AMD) that progressed despite a single intravitreal injection of pegaptanib
      sodium (Macugen) six weeks earlier. DESIGN: Interventional case report. METHODS:
      A 62-year-old man and a 76-year-old woman with occult and minimally classic
      lesions, respectively, each received a single injection of intravitreal
      pegaptanib. RESULTS: Within six weeks of an intravitreal pegaptanib injection,
      the choroidal neovascularization (CNV) progressed. In one eye, the chronic occult
      lesion developed subfoveal classic CNV. In the other eye, the classic component
      of the minimally classic lesion tripled in size. CONCLUSIONS: A single dose of
      intravitreal pegaptanib was not effective in these two patients at six weeks.
      This report reminds the ophthalmologist to consider obtaining a fluorescein
      angiogram during follow-up after an intravitreal pegaptanib injection to monitor
      CNV lesion characteristics, particularly if the visual acuity decreases.

PMID- 17011869
TI  - Intravitreal injection of bevacizumab (Avastin) as adjunctive treatment of
      proliferative diabetic retinopathy.
AB  - PURPOSE: To report the use of intravitreal bevacizumab (Avastin) as an adjunctive
      treatment for proliferative diabetic retinopathy (PDR). DESIGN: Retrospective
      case review. METHODS: Institutional review board approval to review patient data
      was obtained for this retrospective study. Three patients underwent intravitreal
      injection of bevacizumab as part of their treatment for PDR after informed
      consent was signed. Each patient also underwent fundus photographs before the
      bevacizumab injection and then one to three weeks after. RESULTS: All three
      patients showed complete regression of their neovascularization elsewhere (NVE)
      and neovascularization of the disk (NVD) between one and three weeks after
      injection. CONCLUSIONS: The speed and degree of neovascular regression after the
      injection of intravitreal bevacizumab may make this procedure an important
      adjunctive treatment in the management of selected cases with severe PDR.

PMID- 17011870
TI  - Retinal vascular abnormalities and prevalence of age-related macular degeneration
      in adult Chinese: the Beijing Eye Study.
AB  - PURPOSE: To evaluate whether retinal vessel abnormalities are associated with
      early or late age-related macular degeneration (AMD) in adult Chinese. DESIGN:
      Population-based prevalence study. METHODS: The Beijing Eye Study included 4439
      (83.4%) subjects of 5324 living in a rural area or urban region of Greater
      Beijing, age older than 40+ years, and invited to participate. The participants
      underwent a detailed ophthalmic examination, including fundus photography. The
      photographs were graded using the Wisconsin Age-Related Maculopathy Grading
      system for evaluation of AMD, and using the Atherosclerosis Risk in Communities
      protocol for assessment of retinal vascular abnormalities. We examined focal and
      generalized arteriolar narrowing, arteriolar sheathing, and arteriovenous
      crossing abnormalities. RESULTS: Fundus photographs were available for 8655 eyes
      of 4376 (98.6%) subjects. Neither early nor late AMD was significantly (P > .15)
      associated with any of the retinal vascular abnormalities. CONCLUSIONS: Retinal
      vascular abnormalities are not markedly associated with the prevalence of early
      or late AMD.

PMID- 17011871
TI  - Rubeosis and anterior segment ischemia associated with systemic cryoglobulinemia.
AB  - PURPOSE: To report two cases of iris neovascularization associated with systemic
      cryoglobulinemia. DESIGN: Retrospective case report. METHODS: Patient chart
      review and review of literature. RESULTS: Two patients with iris
      neovascularization in the absence of retinal ischemia were subsequently found to
      have systemic cryoglobulinemia. Successful treatment of one patient's underlying
      lymphoma led to stabilization and resolution of neovascularization. CONCLUSIONS:
      Systemic cryoglobulinemia may be associated with anterior segment ischemia and
      neovascularization, and should be considered in the differential diagnosis of
      iris neovascularization in the absence of apparent retinal ischemia.

PMID- 17011872
TI  - Transpupillary argon laser photocoagulation and Nd:YAG laser cystotomy for
      peripheral iris pigment epithelium cyst.
AB  - PURPOSE: To report the use of a combination of transpupillary argon laser
      photocoagulation and Nd:YAG laser cystotomy in the treatment of peripheral iris
      pigment epithelium (IPE) cyst. DESIGN: Case report. METHODS: A 23-year-old man
      presented with a one-month history of blurred vision and pain in the right eye.
      Slit-lamp biomicroscopy and gonioscopy revealed, in the iridociliary sulcus, a
      large clear IPE cyst, which was demonstrated by ultrasound biomicroscopy (UBM). A
      combination of transpupillary photocoagulation to devitalize the epithelial
      lining and neodymium-doped yttrium aluminum garnet (Nd:YAG) laser cystotomy to
      drain the cyst was engaged. RESULTS: Laser treatment resulted in vanishing of the
      cyst and disappearance of the subject symptoms. Two months postoperatively, no
      evidence existed of the iris pigment cyst regrowth. CONCLUSIONS: The minimal
      invasiveness of the combination of transpupillary laser photocoagulation and
      cystotomy yielded a favorable result. This procedure may be an alternative to
      conservative regimen if IPE cyst is clearly defined and readily seen.

PMID- 17011873
TI  - Bilateral diffuse melanocytic proliferation associated with ovarian carcinoma and
      metastatic malignant amelanotic melanoma.
AB  - PURPOSE: To report a case of metastatic malignant amelanotic melanoma to the skin
      from a patient diagnosed with bilateral diffuse uveal melanocytic proliferation
      (BDUMP). This dermatological finding is a unique phenomenon associated with
      BDUMP. DESIGN: Retrospective case report. METHODS: We studied the case of a 66
      year-old Caucasian woman with gradual onset of blurred vision in her right eye
      followed by her left eye. She had previously been diagnosed with ovarian
      carcinoma, and findings of funduscopic examinations were consistent with BDUMP.
      Metastatic examination revealed no evidence of liver involvement. Clinical and
      histopathological examinations of both enucleated eyes were consistent with
      BDUMP. RESULTS: The hematoxylin and eosin, S-100, and HMB-45 stains were
      consistent with metastatic malignant amelanotic melanoma to the skin.
      CONCLUSIONS: Although believed to have a low potential for metastasis, patients
      should be monitored and evaluated regularly to detect any new lesions not
      associated with their primary inciting carcinoma.

PMID- 17011874
TI  - Metaplastic squamous epithelial downgrowth after clear corneal cataract surgery.
AB  - PURPOSE: To report a case of metaplastic squamous epithelial downgrowth after
      cataract surgery. DESIGN: Interventional case report. METHODS: Clinical,
      laboratory, and histologic findings are presented. Our study is in compliance
      with institutional review board guidelines. RESULTS: A 76-year-old man developed
      anterior chamber inflammation five months after uncomplicated clear corneal
      cataract surgery. Despite antimicrobial and anti-inflammatory therapies, the
      inflammation persisted. An extensive examination failed to demonstrate an
      infectious etiology or lymphoma. Subsequently, the patient developed an incipient
      limbal lesion and iris mass. Immunostaining of a biopsy specimen from the iris
      mass indicated an epithelial-derived tumor. The prephthisical and painful eye was
      enucleated; histopathology of the globe revealed a contiguous lesion extending
      from the limbal mass to the iris tumor through the surgical incision site, a
      finding consistent with metaplastic squamous epithelial downgrowth. Systemic
      evaluation was negative. CONCLUSIONS: After intraocular surgery, metaplastic
      epithelial downgrowth may occur as a consequence of occult ocular surface
      squamous neoplasia and masquerade as chronic inflammation; clinicians should be
      aware of this rare complication.

PMID- 17011875
TI  - Giant orbital cysts after strabismus surgery.
AB  - PURPOSE: To describe a rarely reported complication of strabismus surgery.
      DESIGN: Observational case series. METHODS: A review of four eyes in three
      patients with orbital cysts following strabismus surgery. RESULTS: Each patient
      had either a symptomatic strabismus or visible mass that brought them to medical
      attention many years, often decades after surgery (mean 34 years). All had some
      degree of incomitancy. During surgery, all cysts were found to be associated with
      the involved rectus muscle. CONCLUSIONS: Orbital cysts are a rarely recognized
      complication of strabismus surgery. However, it should be considered in the
      differential of orbital cysts after strabismus surgery because of the risk of
      muscle damage during surgical excision.

PMID- 17011876
TI  - Real depth vs randot stereotests.
AB  - PURPOSE: To compare the performance of real depth and Randot stereotests in
      strabismic and nonstrabismic patients. DESIGN: Observational case series.
      METHODS: Stereoacuity was tested in 182 patients with a variety of strabismic
      conditions, using the Frisby-Davis 2 (FD2) distance stereotest, the near Frisby
      (nF) (both real depth tests), the Preschool Randot (nR), and Distance Randot (dR)
      tests (both based on Polaroid vectographs). RESULTS: Patients appreciated finer
      disparities with the nF test than the nR test at near and with the FD2 test than
      the dR test at distance. CONCLUSIONS: The type of stereotest influences
      measurable thresholds, and the results from different tests are not
      interchangeable. The choice of test should depend on the question being asked; nF
      and FD2 would be appropriate for determining presence or absence of stereopsis
      and best measurable stereopsis. The more rigorous Randot tests would be
      appropriate for determining subtle changes.

PMID- 17011877
TI  - Anti-beta2 glycoprotein 1 and the anti-phospholipid syndrome.
AB  - PURPOSE: To describe a patient who presented with bilateral retinal vascular
      occlusion and the use of anti-beta2 glycoprotein 1 (GPI) antibody testing in the
      diagnosis of antiphospholipid syndrome. DESIGN: Observational case report.
      METHODS: Hematological investigations were performed on a 49-year-old man who
      presented with rapid onset of bilateral severe central retinal vein occlusion.
      RESULTS: Lupus anticoagulant and anticardiolipin antibody testing was negative.
      Markedly raised titers of anti-beta2 GPI antibodies were detected on two separate
      occasions. CONCLUSIONS: The raised titers of anti-beta2 GPI antibodies were
      considered to strongly suggest an underlying diagnosis of the antiphospholipid
      syndrome.

PMID- 17011878
TI  - Screening genes of the retinoid metabolism: novel LRAT mutation in leber
      congenital amaurosis.
AB  - PURPOSE: To evaluate the mutation prevalence and phenotype in genes involved in
      the ocular retinoid metabolism. DESIGN: We analyzed LRAT, encoding the lecithin
      retinol acyltransferase, and RDH10, a retinal pigment epithelium-specific retinol
      dehydrogenase. METHODS: We screened by denaturing-high performance liquid
      chromatography (D-HPLC) and direct sequencing all coding exons of LRAT and RDH10
      in 216 patients, including 134 with simplex or multiplex retinitis pigmentosa and
      82 with various types of flecked retinal dystrophies. RESULTS: Only nonpathogenic
      variants were found in this series. In an additional 2.5-year-old patient
      presenting with an "RPE65" phenotype (night blindness, photoattractivity, and
      visual improvement several months after birth), we discovered a homozygous
      deletion in LRAT (c.217_218delAT) leading to a premature stop at codon 120.
      CONCLUSIONS: The phenotype of patients with mutations in LRAT is similar to that
      of patients with mutations in RPE65, suggesting the need to systematically screen
      both genes in case of typical phenotype.

PMID- 17011879
TI  - Ocular findings among thalassemia patients.
AB  - PURPOSE: The study aims at studying the ophthalmologic status in a group of
      thalassemia patients. DESIGN: A cross-sectional study. METHODS: Eighty-four
      thalassemia patients were randomly selected and underwent an ophthalmologic
      examination. RESULTS: Visual acuity (VA) was affected in 13 patients and retinal
      pigment epithelial changes were detected in 21 patients. Decrease in VA was found
      to be significantly associated with type of thalassemia (P < .05) and having
      splenectomy (P = .05). Retinal pigment epithelium changes, conversely, were
      significantly associated with type of iron chelation. CONCLUSIONS: The occurrence
      of ophthalmologic problems in Lebanese thalassemic patients is common. These
      patients, especially those with severe anemia, should be screened for such
      complications. However, the results were not conclusive on whether these
      complications are attributable to the anemia, the iron overload, or a side effect
      of the iron chelating agents.

PMID- 17011880
TI  - Allergic contact dermatitis caused by topical eye drops.

PMID- 17011881
TI  - How to measure the whole ocular rigidity?

PMID- 17011883
TI  - Topical dorzolamide for the treatment of cystoid macular edema in patients with
      retinitis pigmentosa.

PMID- 17011885
TI  - Bilateral lateral rectus recession vs unilateral recess-resect procedure for
      exotropia with a dominant eye.

PMID- 17011887
TI  - Retinal blood flow and macular edema after radial optic neurotomy for central
      retinal vein occlusion.

PMID- 17011888
TI  - Intravitreal triamcinolone for the treatment of ischemic macular edema associated
      with branch retinal vein occlusion.

PMID- 17011891
TI  - Transcaruncular orbital decompression: an alternative procedure for graves
      ophthalmopathy with compressive optic neuropathy.

PMID- 17011894
TI  - The discovery of new knowledge: our scientific mission.

PMID- 17011895
TI  - Outcomes of laparoscopic paraesophageal hernia repair in elderly and high-risk
      patients.
AB  - BACKGROUND: This study examines the impact of age and comorbidities on
      complications and outcomes of laparoscopic (Lap) paraesophageal hernia (PEH)
      repair. METHODS: Data were collected prospectively on all patients who underwent
      Lap PEH repair from January 1995 through June 2005. Pre- and postoperative
      variables including complications were analyzed. Patients were stratified by age
      (Group [Gr.] 1, <65 years; Gr. 2, 65 to 74 years; Gr. 3, >/=75 years) and
      American Society of Anesthesiology (ASA) class (1 and 2 vs 3 and 4). Statistical
      analysis was performed using 1-way ANOVA, chi-square, and Fisher exact test.
      RESULTS: Overall, 171 patients underwent Lap PEH repair. Mean patient age was 65
      +/- 15 years, mean ASA class 2.4 +/- 0.5, gender 72% female, and mean operating
      time 173 +/- 49 min. Patients in Gr. 3 had a significantly higher ASA class (Gr.
      1, 2.3 +/- 0.6; Gr. 2, 2.5 +/- 0.5; Gr. 3, 2.6 +/- 0.5) and longer postoperative
      length of stay (LOS) compared with Gr. 1 (P < 0.05). Esophageal lengthening was
      required in 10.4% of patients in Gr. 3 versus 2.6% in Gr. 1 and 2.1% in Gr. 2 (P
      = 0.079). Total complication rates were 17.1% in Gr. 1, 22.4% in Gr. 2, and 27.7%
      in Gr. 3 (P = not significant [NS]). Most complications were minor; grade 2 or
      higher complications occurred in 10.5% of patients in Gr. 1, 8.3% in Gr. 2, and
      8.5% in Gr. 3 (P = NS). There was 1 death (Gr. 2) on postoperative day 18 due to
      a myocardial infarction (mortality rate = 0.6%). Mean follow-up was 25.3 +/- 20.6
      months. Postoperative symptoms of heartburn and regurgitation were similar
      between groups as was antisecretory medication use. Anatomic failure of the
      repair occurred in 23.7% of patients with adequate follow-up: 26.7% in Gr. 1,
      15.4% in Gr. 2, and 27.8% in Gr. 3 (P = NS). Reoperation was performed in 1 of 32
      (3.1%) failures. CONCLUSIONS: Lap PEH repair is safe in elderly and properly
      selected high-risk patients, although complication rates are higher than in
      younger patients. Most patients have a good symptomatic outcome irrespective of
      their age, but the anatomic recurrence rates remain a concern for all age groups.

PMID- 17011896
TI  - Selective or routine axillary disease staging for patients with clinically lymph
      node-negative breast cancer?
AB  - BACKGROUND: Although sentinel lymph node biopsy (SLNB) has become the standard
      for patients with clinically lymph node-negative breast cancer, less than one
      third of patients who undergo SLNB will have lymph node metastases. Therefore, we
      hypothesized that a subset of patients in whom SLNB can be avoided can be
      identified before operation. METHODS: We prospectively studied 220 patients with
      early stage breast cancer who underwent SLNB. We analyzed primary tumor features,
      biologic markers, and demographic data. RESULTS: Overall, 31% of the patients had
      lymph node metastases. Although patients with lymph node metastases had larger
      neoplasms than patients who were lymph node negative (mean, 2.3 +/- 0.1 cm versus
      1.5 +/- 0.1 cm; P < .0001), 10% of patients with T1a tumors, 19% of patients with
      T1b tumors, and 30% of patients with T1c tumors had lymph node metastases.
      Palpable tumors were lymph node positive in 41% of patients versus 17% for
      nonpalpable tumors (P = .0001). Lymph node metastases were seen in 71% of
      patients with tumor angio or lymphatic invasion versus 17% of patients without (P
      < .0001). Seventy-five percent of patients with an increased preoperative serum
      CA 27.29 had lymph node metastases, and the mean levels were greater among
      patients who were lymph node positive (27 U/ml +/- 2 versus 20 +/- 1; P = .0002).
      There was no significant association between any other demographic, histologic,
      or molecular feature that was investigated and lymph node metastases. CONCLUSION:
      We did not identify histologic, demographic, or molecular variables that can
      exclude the risk of associated lymphatic metastases reliably. Furthermore, not
      all predictive factors are known before the operation (eg, whether the tumor is
      T1a or T1b). Therefore, we recommend that SLNB be performed in all patients with
      clinically lymph node-negative invasive breast cancer.

PMID- 17011897
TI  - Improving operating room efficiency through process redesign.
AB  - BACKGROUND: Operating rooms (ORs) are important resources for patient care and
      revenue, yet a significant portion of OR time is taken up by nonoperative
      activities. We hypothesized that redesigning the process that occurs between
      operations would lead to a decrease in nonoperative time (NOT = room turnover
      time plus anesthesia induction and emergence time). METHODS: Following a 3-month
      multidisciplinary planning process, a prospective study to reduce NOT was
      initiated in 2 of 17 ORs at a tertiary care academic medical center. Unlike
      previous reports, which have limited the number of participants, we constructed a
      process that was restricted only by case duration. The plan focused on minimizing
      nonoperative tasks in the OR, effecting parallel performance of activities, and
      reducing nonclinical disruptions. Eligible cases were those with an estimated
      operative time of 2 hours or less. A target NOT of 35 minutes was established.
      Cases of similar duration in the remaining ORs served as a concurrent control
      group. RESULTS: Twenty-three surgeons, 13 anesthesiologists, and 11 nurses worked
      in the project ORs over a 3-month period. Residents participated in all cases.
      There was a significant reduction in NOT (42.2 +/- 12.9 vs 65 +/- 21.7 minutes),
      turnover time (26.4 +/- 11.2 vs 42.8 +/- 21.7 minutes), and anesthesia-related
      time (16.9 vs 21.9 minutes, all P < .001) in the project rooms compared with
      cases of similar duration in control ORs. Process-related delays were identified
      in 70% of cases when NOT exceeded the 35-minute target. CONCLUSIONS: These
      results demonstrate that a coordinated multidisciplinary process redesign can
      significantly reduce NOT. This process is applicable to most ORs and has optimal
      benefit for cases of 2 hours or less in duration. The high percentage of residual
      process-related delays suggests that further improvements can be anticipated.

PMID- 17011898
TI  - The malabsorptive very, very long limb Roux-en-Y gastric bypass for super
      obesity: results in 257 patients.
AB  - BACKGROUND: For the past 11 years, we have used a malabsorptive form of Roux-en-Y
      gastric bypass (RYGB), the "very, very long limb" RYGB, for selected patients
      with BMIs >50 kg/m(2) and in highly selected patients with BMI <50 kg/m(2). This
      modified distal gastric bypass establishes a 100-cm common channel (for digestion
      and absorption) and a "very, very" long Roux limb of 400 to 500 cm. METHODS: To
      determine long-term efficacy and complications, we followed prospectively 257
      consecutive patients; 188 (73%) participated in a postoperative survey. RESULTS:
      Of the patients, 60% were female; overall age (x +/- SD) was 45 +/- 11 years, and
      BMI was 61 +/- 11 kg/m(2). Operative mortality was 1% with substantive
      postoperative morbidity occurring in 13%. Eighty-two percent of patients
      returning the survey an average of 48 months postoperatively (range, 12 to 148
      months) lost >50% of excess body weight; BMI at follow-up was 37 +/- 9 kg/m(2).
      Resolution of comorbidities included diabetes mellitus (94%), hypertension (65%),
      sleep apnea (48%), and asthma (30%). Side effects included mild food intolerance
      (82%), occasional loose or watery stools (71%), nephrolithiasis (16%), and
      symptomatic steatorrhea (5%). Nine patients (4%) who developed or were developing
      impending protein/calorie malnutrition required proximal relocation of the
      enteroenterostomy with symptom resolution. CONCLUSIONS: Overall, 90% were
      satisfied with the operation, and 93% would recommend it to a friend. The very,
      very long limb RYGB is relatively safe and effective and has acceptable side
      effects in the treatment of selected patients with super obesity (BMI >50).
      Because of the possibility of malabsorptive sequelae, patients should be selected
      based on degree of medical sophistication, insight, and compliance.

PMID- 17011899
TI  - Laparoscopic gastric bypass: risks vs. benefits up to two years following surgery
      in super-super obese patients.
AB  - BACKGROUND: Super-super obesity (body mass index [BMI] >/= 60 kg/m(2)) is thought
      to be a risk factor for complications and mortality in laparoscopic Roux-en-Y
      gastric bypass. Excess weight loss has been demonstrated to be diminished
      compared with less obese patients following surgery. However, we hypothesize that
      super-super obese patients who undergo laparoscopic gastric bypass can realize
      major improvements in their health and a good quality of life without a
      significantly increased risk of complications when compared with less obese
      patients. METHODS: From July 2002 to July 2005, University of Wisconsin Health
      bariatric surgeons performed 288 consecutive laparoscopic Roux-en-Y gastric
      bypass procedures. Patients were divided into 2 groups: BMI >/= 60 kg/m(2) (n =
      28) and BMI < 60 kg/m(2) (n = 260). The groups were compared at defined time
      intervals during a 2-year period following surgery. Comparison criteria included
      complications, weight loss, comorbidities, and quality of life. RESULTS: Both
      groups had similar morbidity and mortality rates. Excess weight loss was shown to
      be less, but total pounds lost were greater, for the super-super obese patients
      at all postoperative time intervals specified for postoperative analysis. Despite
      this fact, overall health improved to a similar degree in each group of patients
      following surgery; both groups also had similar Moorehead-Ardelt quality of life
      scores. Using the Bariatric Analysis and Reporting Outcome System (BAROS) to
      categorize outcomes, the average result for a patient in either group of patients
      would be considered "very good" at 1 year following surgery. CONCLUSIONS:
      Laparoscopic Roux-en-Y gastric bypass can be accomplished safely even in
      extremely obese patients. Although excess weight loss in the super-super obese is
      diminished postoperatively when compared with less obese patients, health is
      improved and quality of life is good regardless of a patient's preoperative BMI.
      Therefore, laparoscopic gastric bypass is a good option even in the extremely
      obese.

PMID- 17011900
TI  - Acute limb ischemia associated with type B aortic dissection: clinical relevance
      and therapy.
AB  - BACKGROUND: The goal of the current study is to characterize the presentation,
      therapy, and outcomes of acute limb ischemia (ALI) associated with type B aortic
      dissection (AoD). METHODS: The prospective/retrospective International Registry
      for Acute Aortic Dissection (IRAD) database and a single institutional database
      were queried for all patients with type B AoD from 1996 to 2002. Univariate and
      multivariate statistics were used to delineate factors associated with morbidity
      and mortality outcomes. RESULTS: According to the IRAD data (n = 458), the mean
      age of patients was 64 years, and 70% were men. The overall mortality was 12%; of
      these, 6% had ALI. Pulse (3-fold) and neurologic deficits (5-fold) were more
      common in those with ALI (P < .001). Endovascular, but not surgical therapy, was
      more commonly performed in patients with ALI compared with those without ALI (31%
      vs 10%, P = .004). No difference in age, race, gender, or origin of dissection
      was observed. ALI was associated with acute renal failure (odds ratio [OR] = 2.7;
      95% confidence interval [CI] 1.1-7.1; P = .048) and acute mesenteric
      ischemia/infarction (OR = 6.9; 95% CI 2.5-20; P < .001). Adjusting for patient
      characteristics, ALI was associated with death (3.5; 95% CI 1.1-10; P = .02). The
      single institution analysis revealed similar patient demographics and mortality
      in 93 AoD patients, of whom 28 had ALI. Aortic fenestration or aorto-iliac
      stenting was the primary therapy in 93%; surgical bypass was used in 7%. Limb
      salvage was 93% in those with ALI at a mean of 18 months follow-up. The number of
      organ systems with malperfusion was 2-fold higher at aortography than suspected
      preprocedure (P = .002). By stepwise regression modeling, mortality was greater
      in those not taking a beta-blocker (OR = 19; 95% CI 3.1-111; P = .001).
      CONCLUSIONS: ALI secondary to AoD is predictive of death and visceral ischemia.
      Endovascular therapy confers excellent limb salvage and allows diagnosis of
      unsuspected visceral ischemia.

PMID- 17011901
TI  - Interventions to improve guideline compliance following coronary artery bypass
      grafting.
AB  - BACKGROUND: Lifestyle modification and appropriate medical therapy improve long
      term outcomes following coronary artery bypass grafting (CABG). Our institutional
      experience suggested that evidence-based recommendations were not being followed
      postdischarge after CABG. We undertook this study to document our rate of
      compliance with evidence-based guidelines and to correct deficiencies in our
      discharge practices. METHODS: Seven evidence-based interventions were studied
      after CABG: (1) institution of beta-blocker therapy, (2) angiotensin-converting
      enzyme (ACE) inhibitor therapy, (3) aspirin, (4) lipid-lowering therapy, (5)
      smoking cessation intervention, (6) heart-healthy diet therapy, and (7) physical
      activity recommendations. The rate of compliance with guidelines in 50 control
      patients was measured at discharge. A multidisciplinary team including cardiac
      surgeons, nurses, dieticians, physical therapists, and clinical pharmacists
      evaluated the guideline compliance in the control group and developed
      interventions to assure guideline compliance at the time of discharge. A
      subsequent study group of 50 patients was then assessed prospectively to measure
      the guideline compliance after institution of intervention programs. The
      multidisciplinary team agreed on predefined acceptable compliance limits as
      follows: (1) >80% of patients receive ACE inhibitors at discharge, (2) 100% of
      patients receive beta-blockers, aspirin, and lipid-lowering agents at discharge,
      and (3) 100% of patients receive lifestyle modification counseling at discharge.
      Compliance with guidelines was defined as documentation in the medical record of
      provision of medications and lifestyle counseling at the time of discharge.
      RESULTS: In the control group, the rate of guideline compliance was surprisingly
      low. Rates of compliance with guidelines increased significantly after the
      multidisciplinary interventions were undertaken. CONCLUSIONS: We conclude that
      compliance with guidelines known to improve long-term outcome is suboptimal after
      CABG. A multidisciplinary intervention program can improve compliance with
      currently accepted guidelines and quality indicators in patients following CABG.

PMID- 17011902
TI  - Analysis of large versus small pheochromocytomas: operative approaches and
      patient outcomes.
AB  - BACKGROUND: Laparoscopic adrenalectomy for small pheochromocytomas, although
      challenging, is widely accepted. However, its application to pheochromocytomas
      larger than 6 cm is questioned due to concerns of malignancy and case complexity.
      Our aim was to examine the impact of pheochromocytoma tumor size (>/=6 cm vs <6
      cm) on operative approach and postoperative patient outcomes. METHODS: A
      retrospective review of adrenalectomies performed at 3 university hospitals over
      1 decade was analyzed. All pheochromocytomas were identified and then divided
      based on size into large (>/=6 cm) and small (<6 cm) groups. We examined patient
      and tumor demographics, pathologic diagnosis, operative approach (laparoscopic vs
      open), postoperative complications, and biochemical cure rates. Data were
      analyzed using the Student t test and Fisher exact test with a P value <.05
      considered significant. RESULTS: From 1995 to 2005, 65 pheochromocytomas were
      resected. Of the total, 38% (n = 25) tumors were >/=6 cm and 62% (n = 40) were <6
      cm. For the large tumors, 1 out of 25 (4%) was malignant, whereas no small tumors
      were malignant. There was no statistically significant increased risk of
      malignancy in tumors >/=6 cm in size (P = .31). Initial operative approach was
      based on surgeon preference. Of the adrenalectomies performed, 88% were
      laparoscopic, with 3 of 25 (12%) large tumors requiring conversion from
      laparoscopic to open for intraoperative bleeding. None of the small tumors
      required conversion. No major postoperative complications (eg, stroke or
      myocardial infarction) occurred in either group. Minor complications (eg, wound
      infections and hematomas) were noted in 16% of large tumors and 12.5% of small
      tumors (P = .45). A total of 96% (24 of 25) patients with large tumors and 100%
      with small tumors showed postoperative biochemical cure. Tumor recurrence was
      noted in 1 patient with a tumor <6 cm. CONCLUSIONS: Pheochromocytomas >/=6 cm
      pose a challenge for laparoscopic resection, and concerns have been raised about
      the validity of this operative approach. This study demonstrates that there is no
      significant difference in the rate of malignancy for pheochromocytomas >/=6 cm
      versus <6 cm. There also were no significant differences identified in
      complication rates, postoperative biochemical cures, or tumor recurrence rates
      between these groups. Laparoscopic resection of pheochromocytomas can be safely
      accomplished regardless of size in centers with surgeons experienced in these
      procedures.

PMID- 17011903
TI  - Current management of pancreatic fistula after pancreaticoduodenectomy.
AB  - BACKGROUND: Pancreatic fistula (PF) is a major and serious complication following
      pancreaticoduodenectomy (PD). The purpose of this study was to outline our
      management of PF after PD. METHODS: A retrospective review of a prospectively
      collected database of 396 patients undergoing PD for various indications at
      Loyola University Medical Center and Hines Veterans Administration Hospital from
      July 1, 1990, to December 31, 2005. Patients were divided group 1 (no PF) and
      group 2 (PF). Each group was compared regarding preoperative, intraoperative, and
      postoperative outcomes. RESULTS: Of the patients included in the study, 65
      patients (16%) developed a PF. PF was more common after PD for ampullary
      neoplasms (28%), duodenal neoplasms (35%), and serous cystic neoplasms (44%), and
      was uncommon after PD for pancreatic cancer (6%). Associated complications with
      PF was 51% when compared with patients with no PF (21%; P </= .001). Duration of
      hospital stay was 16 days in PF versus 9 days in no PF (</=.001). Intraoperative
      blood loss was greater in the PF versus no PF group (P = .01). Clinically serious
      postoperative complications in the PF versus no PF group were mortality (P =
      .03), intraabdominal abscess (P </= .001), wound infection (P </= .001),
      hemorrhage (P = .01), cardiac (P </= .001), bile leak (P </= .001), and
      reoperation (P = .02). Of the 62 surviving patients with PF, 36 (58%) were
      treated with maintenance of oral diet, 25 (40%) with parenteral nutrition, and 1
      (1.6%) required surgery for closure of PF. CONCLUSIONS: PF is a serious
      complication after PD and is associated with substantial mortality and other
      complications. The majority of patients with PF can be managed conservatively
      with either maintenance of oral diet or parenteral nutrition until closure of the
      PF.

PMID- 17011904
TI  - Enterocutaneous fistula: are treatments improving?
AB  - BACKGROUND: We studied the etiology, treatment, and outcome of enterocutaneous
      fistulas in 106 patients to evaluate our current practice and the impact of newer
      therapies-octreotide, wound vacuum-assisted closure (VAC), and fibrin glue-on
      clinical outcomes. Review of the literature and our own 1990 study indicate a
      mortality rate of 5% to 20% for enterocutaneous fistula, and a healing rate of
      75% to 85% after definitive surgery. METHODS: We reviewed all cases of
      gastrointestinal-cutaneous fistula from 1997 to 2005 at 2 large teaching
      hospitals. We identified 106 patients with enterocutaneous fistula; patients with
      irritable bowel disease and anorectal fistulas were excluded. RESULTS: The origin
      of the fistula was the small bowel in 67 patients, colon in 26, stomach in 8, and
      duodenum in 5. The etiology of the fistula was previous operation in 81 patients,
      trauma in 15, hernia mesh erosion in 6, diverticulitis in 2, and radiation in 2.
      Of the 106 patients in the study, 31 had a high output fistula (greater than 200
      mL/day), 44 had a low output fistula, and, in 31 patients, the fistula output was
      low but there was no record of volume. Initial treatment was nonoperative except
      for patients with an abscess who needed urgent drainage. In 24 patients, the
      effect of octreotide was monitored: in 8 patients, fistula output declined; in 16
      patients, octreotide was of no benefit. Fibrin glue was used in 8 patients and
      was of benefit to 1. The wound VAC was used in 13 patients: 12 patients still
      required operative repair of the fistula, whereas the fistula was healed in 1
      patient. The main benefit of the VAC system was improved wound care in all
      patients before definitive surgery. Total parenteral nutrition was used in most
      patients to provide nutritional support. Operative repair was performed in 77
      patients and was successful in 69 (89%), failing in 6 patients with persistent
      cancer or infection. Nonoperative treatment was used in 29 patients and resulted
      in healing in 60%. Of 106 patients, 7 (7%) died of fistula complications. The
      cause of death was persistence or recurrence of cancer in 4 patients and
      persistent sepsis in 3. CONCLUSION: Enterocutaneous fistula continues to be a
      serious surgical problem. The wound VAC and fibrin glue had anecdotal successes
      (n = 2), and one-third of patients responded to octreotide. We believe that
      octreotide should be tried in most patients and that the wound VAC has a role in
      selected patients. Although 7% overall mortality is lower than in previous
      studies, the number managed without operation (27%) remains the same. In addition
      to early control of sepsis, nutritional support, and wound care, a well-timed
      operation was the most effective treatment.

PMID- 17011905
TI  - Hypertonic saline resuscitation improves intestinal microcirculation in a rat
      model of hemorrhagic shock.
AB  - BACKGROUND: Conventional resuscitation (CR) from hemorrhagic shock (HS) often
      restores and maintains hemodynamics but fails to restore intestinal perfusion.
      Post-CR intestinal ischemia has been implicated in the initiation of a gut
      derived exaggerated systemic inflammatory response and in the progressive organ
      failure following HS. We propose that intestinal ischemia can be prevented with
      hypertonic saline resuscitation (HTSR). METHODS: Anesthetized male Sprague-Dawley
      rats (200 to 215 g) were hemorrhaged to 50% of mean arterial pressure (MAP) for
      60 minutes and randomly assigned to 1 of the resuscitation groups (n = 7 each):
      Group I: sham operation and no HS; Group II: HS + CR with the return of the shed
      blood + 2 volumes of normal saline (NS); Group III: HS + return of the shed blood
      + hypertonic saline (HTS); (7.5 % NaCl, 4 ml/kg); Group IV: HS + HTS, then return
      of the shed blood after 60 minutes; Group V: HS + HTS, then 1 volume of NS after
      60 minutes. Microvascular diameters of inflow (A1) and proximal and distal
      premucosal arterioles (A3) in terminal ileum and flow in A1 were measured using
      in vivo videomicroscopy and optical Doppler velocimetry. Hematocrit, plasma
      osmolarity, and electrolytes were measured in Groups II and III. RESULTS: HS
      caused a selective vasoconstriction in A1 arterioles that was not seen in the
      premucosal arterioles. CR restored and maintained MAP and caused generalized,
      progressive vasoconstriction at all intestinal arteriolar levels that is
      associated with hypoperfusion. HTSR failed to restore or maintain MAP or
      intestinal A1 arteriolar blood flow until the shed blood was returned. However,
      HTSR prevented the post-resuscitation, premucosal vasoconstriction and produced
      an insidious selective vasodilation in the A3 arterioles, which was most
      significant with early blood return (Group III). This selective arteriolar
      vasoactivity was associated with a significant improvement of endothelial cell
      function. Plasma hyperosmolality and hypernatremia persisted during the entire 2
      hours post-resuscitation with HTS. CONCLUSIONS: Small-volume HTSR can be used as
      a resuscitation regimen at the trauma scene and for selective clinical conditions
      where hypotensive resuscitation is indicated. HTSR improves intestinal perfusion
      by selective vasodilation of the precapillary arterioles even at MAP close to
      shock levels.

PMID- 17011906
TI  - Differences and similarities between rural and urban operations.
AB  - BACKGROUND: The importance of rural operations is magnified by super
      specialization, uneven geographic distribution, and special educational needs.
      Definition of practice patterns and quality measures are needed. METHODS: A
      statewide network of 60 operative specialists studied costs, quality, and
      outcomes in 17,319 patients undergoing 46 different specialty operations between
      1998 and 2003, comparing 9,544 rural to 7,775 urban patients. These data are
      augmented by additional data from 5,339 operative patients in 2004. RESULTS: Both
      high volume rural and urban surgeons achieved fewer deaths than less frequent
      practitioners of colon or rectal resections (2/309 vs 5/167). Urban surgeons had
      sicker patients undergoing more extensive procedures, and used fewer
      consultations, but had more complications and reoperations. Laparoscopic
      cholecystectomy had similar outcomes with 5 deaths among 1,788 patients. Urban
      surgeons converted to an open procedure more frequently, whereas rural surgeons
      used hepatobiliary iminodiacetic acid (HIDA) scans as indication for
      cholecystectomy more often (P < .01). Indications for upper and lower endoscopy
      varied, but abnormalities were noted in 64%; only 11 of 6,938 patients undergoing
      endoscopy were admitted for complications, 5 required operations, 3 due to
      totally obstructing cancers. Hysterectomy, urologic procedures, and tympanostomy
      had admission/readmission rates as low as 1/400. Documented patient preoperative
      education occurred in 94% of both groups. Overall, performance measures were
      addressed more consistently by rural surgeons (P < .001). CONCLUSIONS: Operative
      practice reaches high standards in both settings; indications for operations
      vary, and rural practice is broader than urban practice. Rural surgeons exceed
      their urban colleagues on some quality process measures.

PMID- 17011907
TI  - Experience with dual kidney transplants from donors at the extremes of age.
AB  - BACKGROUND: Dual kidney transplantation (DKT) from donors at the extremes of age
      represents one approach to expanding the organ donor pool. The purpose of this
      study was to review our experience with DKT from older donors and en bloc KT
      (EBKT) from small pediatric donors. METHODS: Deceased donor KTs performed at our
      center between October 2001 and November 2005, were reviewed retrospectively. If
      the calculated creatinine clearance in an expanded criteria donor was <65 mL/min,
      then the kidneys were transplanted dually into a single adult recipient. If a
      pediatric donor weighed <15 kg, then the kidneys were transplanted en bloc. In
      both instances, low-risk recipients were chosen (primary transplant, low
      sensitization, body mass index <25 kg/m(2), human leukocyte antigen matching).
      Donor, recipient, and transplant characteristics, waiting time, and outcomes were
      examined. RESULTS: Of a total of 279 deceased donor KTs during the 49-month study
      period, 15 (5%) recipients underwent DKT and 5 (2%) underwent EBKT. Mean donor
      age was 65.4 years and 21.4 months in the DKT and EBKT groups, respectively.
      Patient survival rates in both groups were 100% with a mean follow-up of 22
      months (minimum, 6 months). Kidney graft survival rates were 80% (12/15) and 60%
      (3/5) in the DKT and EBKT groups, respectively. The combined incidence of delayed
      graft function was 10%. Mean 12-month glomerular filtration rates were 46 mL/min
      and 66 mL/min in the DKT and EBKT groups, respectively. CONCLUSIONS: DKT using
      kidneys from marginal elderly donors and EBKT from small pediatric donors appear
      to offer a viable option to counteract the shortage of acceptable kidney donors.

PMID- 17011908
TI  - Effect of vitamin E on tamoxifen-treated breast cancer cells.
AB  - BACKGROUND: Induction of apoptosis by tamoxifen has been postulated to involve
      oxidative stress. Tamoxifen (TAM) may act on estrogen receptors (ER) located in
      the plasma membrane. Our hypothesis that supplemental antioxidant vitamin E
      (alpha-tocopherol) acts at the plasma membrane to alter the effectiveness of
      tamoxifen was tested in ER-positive breast cancer cell lines, MCF-7 and T47D.
      METHODS: Cells were treated in vitro with 20-muM TAM alone and in combination
      with 10-muM alpha-tocopherol (AT). Estrogen growth signals were quantified by
      immunohistochemical staining for the mitogen-activated protein kinase p-ERK.
      Rapid changes in intracellular calcium were detected in TAM-treated MCF-7 and T
      47D cells by fluorescence microscopy of cells loaded with the calcium-sensitive
      dye Fluo 4AM. Apoptosis was assayed by flow cytometry. RESULTS: Proliferating
      cells in normal medium exhibited strong p-ERK staining. Addition of TAM abolished
      p-ERK staining and caused cell rounding and death. The addition of AT led to the
      restoration of cell proliferation and p-ERK expression even in the presence of
      high-dose TAM. Intracellular calcium rapidly increased in MCF-7 and T47D cells
      upon exposure to TAM, followed by an increase in caspase activation and eventual
      apoptosis. The increase in intracellular calcium was abolished by the addition of
      10muM AT to TAM, and pan-caspase staining decreased at 5 hours from 72% to 41%.
      CONCLUSIONS: These studies suggest that supplemental vitamin E decreases the
      inhibitory effect of TAM on the proliferation of ER+ breast cancer cells and
      eliminates the rapid rise in intracellular calcium that leads to apoptosis
      stimulated by TAM. The use of vitamin E acetate supplements may be inadvisable
      for women taking tamoxifen.

PMID- 17011909
TI  - Surgeon communication behaviors that lead patients to not recommend the surgeon
      to family members or friends: Analysis and impact.
AB  - BACKGROUND: This study analyzes specific elements of physician communication that
      lead patients to not recommend surgeons to family members or friends (FMoFs).
      METHODS: Patients completed questionnaires after surgery clinic encounters.
      Questionnaires addressed whether surgeons used optimal communication behaviors
      and whether patients would recommend the surgeon. RESULTS: A total of 1,514
      questionnaires were completed for 39 surgeons. Patients reported the following
      communication lapses: failure to ask whether the patient had questions (6.9% of
      occasions), failure to sit down (6.5%), use of words patients could not
      understand (5%), failure to educate patients about their condition (4.3%),
      failure to introduce themselves (4%), lack of interest in patients as persons
      (2.4%), and inadequacies in answering questions (2%). Surgeons omitted at least
      one of these optimal behaviors in 16.3% of encounters. Surgeons were not
      recommended in 1.7% of encounters. Twelve surgeons (31%) were not recommended on
      at least 1 occasion. Behaviors omitted most commonly in encounters where patients
      wouldn't recommend surgeons included failure to show interest in the patient
      (52%), explain their medical condition (52%), invite questions (40%), and answer
      questions (36%). CONCLUSIONS: Extrapolating these results to 1,618 patient
      visits/surgeon/year, results in the following number of patients annually who do
      not recommend their surgeons: 15 for failure to adequately explain their medical
      condition, 15 for failure to show interest in them, 11 for failure to ask if the
      patient had questions, and 10 for failure to answer questions. Considering the
      ripple effect due to the number of a patient's FMoFs, surgeons should be aware of
      the significant impact of even occasional lapses in optimal communication
      behaviors.

PMID- 17011910
TI  - Improved outcome of adult blunt splenic injury: a cohort analysis.
AB  - BACKGROUND: The purpose of this study was to review our 15-year experience in the
      treatment of blunt splenic injury in adults. Our hypothesis was that the
      implementation of a change in practice, with stress on splenic preservation and
      splenic artery embolization for the management of splenic injury, would result in
      improved splenic salvage rates without negatively affecting mortality rates.
      METHODS: A retrospective cohort analysis was performed on all consecutive adults
      with blunt splenic injury who were admitted to a Level One Trauma Center. The
      cohorts were defined by 2 separate 7.5-year periods (1991-1998 and 1998-2005).
      RESULTS: Six hundred twenty-five patients with blunt splenic trauma were
      identified; 403 patients who were treated from 1998 to 2005 were compared with
      222 patients whose cases had been reviewed previously (1991 to 1998). The present
      cohort differed in age (35 vs 40 years; P < .001) and injury severity score (27
      vs 21; P < .0001). Nonoperative treatment was implemented in 136 patients (61%)
      in the initial cohort and 344 patients (85%) in the present cohort. The frequency
      of splenic artery embolization increased from 2.7% to 22.6% (P < .001). The
      success of nonoperative management increased from 77% to 96% (P < .001); the
      splenic salvage rate for all patients improved from 57% to 88% (P < .0001).
      Hospital mortality rates decreased from 12% to 6% (P < .001), and the mean
      hospital length of stay decreased from 15 to 9 days (P < .001). CONCLUSION: These
      results demonstrate that the success of nonoperative management and the splenic
      preservation for blunt injury has improved over time. This improvement correlated
      with a greater use of splenic artery embolization.

PMID- 17011911
TI  - Utilization of standardized patients to evaluate clinical and interpersonal
      skills of surgical residents.
AB  - BACKGROUND: This project was designed to determine the growth of interpersonal
      skills during the first year of a surgical residency. METHODS: All categorical
      surgical residents were given a clinical skills examination of abdominal pain
      using standardized patients during their orientation (T1). The categorical
      residents were retested after 11 months (T2). The assessment tool was based on a
      12-item modified version of the 5-point Likert Interpersonal Scale (IP) used on
      the National Board of Medical Examiners prototype Clinical Skills Examination and
      a 24-item, done-or-not-done, history-taking checklist. Residents' self-evaluation
      scores were compared to standardized patients' assessment scores. Data were
      analyzed using the Pearson correlation coefficient, Wilcoxon signed rank test,
      Student t test, and Cronbach alpha. RESULTS: Thirty-eight categorical residents
      were evaluated at T1 and T2. At T1, in the history-taking exercise, the scores of
      the standardized patients and residents correlated (Pearson = .541, P = .000). In
      the interpersonal skills exercise, the scores of the standardized patients and
      residents did not correlate (Pearson = -0.238, P = .150). At T2, there was a
      significant improvement in the residents' self-evaluation scores in both the
      history-taking exercise (t = -3.280, P = .002) and the interpersonal skills
      exercise (t = 2.506, P = 0.017). In the history-taking exercise, the standardized
      patients' assessment scores correlated with the residents' self-evaluation scores
      (Pearson = 0.561, P = .000). In the interpersonal skills exercise, the
      standardized patients' assessment scores did not correlate with the residents'
      self-evaluation scores (Pearson = 0.078, P = .646). CONCLUSIONS: Surgical
      residents demonstrate a consistently low level of self-awareness regarding their
      interpersonal skills. Observed improvement in resident self-evaluation may be a
      function of growth in self-confidence.

PMID- 17011912
TI  - Decreased progression of postinjury lung dysfunction to the acute respiratory
      distress syndrome and multiple organ failure.
AB  - BACKGROUND: Postinjury organ dysfunction is a result of unbridled systemic
      hyperinflammation. According to the two-event construct, patients are
      resuscitated into an early vulnerable window of systemic hyperinflammation
      (primed) in which a second otherwise innocuous event precipitates uncontrolled
      hyperinflammation, leading to secondary organ damage and dysfunction (activated).
      Recent efforts to decrease postinjury morbidity have focused on limiting the
      potential of second events and systemic inflammation. We hypothesized that the
      collective effects of recently implemented therapeutic strategies have resulted
      in decreased activation of the systemic inflammatory response relative to priming
      in recent years. METHODS: Data were collected prospectively on trauma patients at
      risk for postinjury multiple organ failure (MOF). Inclusion criteria were age >15
      years, trauma intensive care unit admission, Injury Severity Score >15 and
      survival >48 hours. Isolated head injuries and head injuries with an extracranial
      abbreviated injury score <2 were excluded. Daily physiologic and laboratory data
      were collected through surgical intensive care unit day 28, and clinical events
      were recorded thereafter until death or hospital discharge. Organ failure was
      characterized with the use of the Denver MOF Scale. Acute respiratory distress
      syndrome (ARDS) was defined according to the consensus definition. RESULTS: Over
      a 6.5-year period 897 patients were studied; 271 (31%) developed ARDS, and 226
      (25%) developed MOF. Early lung dysfunction, as a measure of systemic priming,
      did not change over the study period. In contrast, the incidence of ARDS and MOF
      decreased from 43% to 25% and 33% to 12%, respectively. The incidence of early
      MOF decreased from 22% to 7% over the study period. CONCLUSIONS: Priming of the
      postinjury inflammatory response is an early event and is primarily influenced by
      the injury itself. Recent advances in postinjury care such as judicious blood
      transfusion, lung protective ventilation, treatment of adrenal insufficiency, and
      tight glucose control are known to attenuate systemic inflammation. Step-wise
      adoption of these therapies is coincident with a decrease in the destructive
      processes resulting in ARDS and MOF. The global effect is a decrease in
      activation of the systemic inflammatory response over recent years.

PMID- 17011913
TI  - Patterns and operative treatment of recurrent Crohn's disease: a prospective
      longitudinal study.
AB  - BACKGROUND: It is believed commonly that Crohn's recurrences always occur at the
      site of a previous intestinal anastomosis; yet this concept is probably
      inaccurate and not mindful of the panintestinal nature of the disease. MATERIALS
      AND METHODS: Between October, 1984 and March, 2003, we carried out 1,132
      procedures (464 for primary and 668 for recurrent disease) on 981 consecutive
      patients. Patients in whom we carried out both the original procedure as well as
      the procedure for recurrent disease constitute this study population. Operative
      procedures for perineal complications were excluded from this analysis. Data were
      accrued prospectively. RESULTS: Seventy-eight patients met the study inclusion
      criteria. They had a total of 149 sites of disease (duodenum, n = 3;
      jejunum/ileum, n = 53; terminal ileum/neo terminal ileum, n = 67; colon and
      rectum, n = 26). One hundred thirty-four sites required operative intervention
      (85 resections and 49 strictureplasties) and 15 did not. Crohn's disease recurred
      in 79 sites after a mean of 48.4 months (range, 1-161 months, median, 41 months).
      Site of operative intervention and operative technique influenced patterns of
      recurrence: when an anastomosis or strictureplasty was constructed with small
      bowel, the majority of recurrences were limited to the anastomotic line (17/29,
      59%); when it was constructed with small bowel and colon, the majority of
      recurrences extended to the proximal limb (29/35, 83%). The difference in
      recurrence pattern is significant (P < .01). In addition, fewer recurrences
      occurred at strictureplasty than resection sites (22/49, 45%, vs 57/85, 70%,
      respectively, P < .05). At the time of the second procedure, 40 additional
      recurrences were identified distant from the original operative site. Four of
      these represented progression of disease at the 15 sites that did not originally
      need operative intervention. Of 119 total recurrences, 115 required 73
      resections, 40 strictureplasties, and 2 other procedures. CONCLUSIONS: The site
      of the original operative intervention is the most common site for recurrence,
      although as many as one-third of recurrences occur separate from it. Pattern of
      recurrence is influenced by site of the operative intervention (anastomotic for
      small bowel, proximal limb for ileocolonic) and by operative technique (fewer
      recurrences occurred at strictureplasty than resection sites). Disease
      progression occurred in 25% of the sites not addressed operatively at the
      original procedure. The operative strategy applied to Crohn's complications in
      different intestinal sites was similar for primary and recurrent disease.

PMID- 17011914
TI  - Improvement in the health-related quality-of-life symptoms of hyperparathyroidism
      is durable on long-term follow-up.
AB  - BACKGROUND: Subjective symptoms such as decreased energy, chronic fatigue, and
      depression are associated with hyperparathyroidism. Studies have shown that these
      symptoms are improved during short-term follow-up after parathyroidectomy. This
      study evaluates the durability of this subjective improvement in quality-of-life
      symptoms in a large population of patients with follow-up greater than 1 year
      after operation. METHODS: Between 2002 and 2005, 258 patients underwent
      parathyroidectomy, 100 (81 females and 19 males) of whom were available for this
      study. The patients were evaluated with a survey based on the Health Outcomes
      Institute Health Status Questionnaire. Some answers were quantified on a 1 to 6
      scale, while others consisted of "yes" or "no" responses. Patients completed a
      questionnaire prior to parathyroidectomy and postoperatively at 1 month, 3 to 6
      months, and 1 to 2 years or greater intervals. Statistical analysis was used to
      detect changes attributable to parathyroidectomy. A P value <.05 was considered
      statistically significant. RESULTS: At 1-month follow-up, patients' perceptions
      of their overall health, energy level, and mood significantly improved. At 6
      month follow-up, significant improvements in muscle strength, health, endurance,
      and relief of anxiety were documented. At the interval of 1 to 2 years, overall
      health, energy level, endurance, and relief of anxiety were improved. There was
      no significant decrement in the quality of life in these patients after
      parathyroidectomy. CONCLUSIONS: Parathyroidectomy for hyperparathyroidism is
      associated with significant lasting improvement in subjective symptoms. The
      potential durable improvement in these quality-of-life symptoms is a valid
      indication for parathyroidectomy.

PMID- 17011915
TI  - The role of parathyroid hormone measurements after surgery for primary
      hyperparathyroidism.
AB  - BACKGROUND: During parathyroidectomy for primary hyperparathyroidism (pHPT),
      intraoperative parathyroid hormone (IOPTH) levels are used to confirm removal of
      all hyperfunctioning parathyroid tissue. The phenomenon of elevated parathyroid
      hormone (PTH) levels with normocalcemia after curative parathyroidectomy, seen in
      up to 40% of patients, continues to be an unexpected and unexplained finding. We
      therefore investigated whether postoperative PTH levels are as reliable as IOPTH
      levels in predicting cure after surgery for pHPT. METHODS: We reviewed our
      prospective database of consecutive patients undergoing surgery for pHPT between
      December 1999 and November 2004. Curative parathyroidectomy was defined as
      normocalcemia 6 months or longer postoperatively. RESULTS: A total of 328
      patients who underwent 330 operations for pHPT had IOPTH measurements and serum
      follow-up calcium levels at 6 months or longer. Surgery was curative in 315
      (95.5%) operations. IOPTH levels correctly predicted operative success in 98.2%
      (positive predictive value [PPV]. Postoperatively, the PPV of a normal PTH level
      at 1 week, 3 months, and 6 months was 97.1%, 97.3%, and 96.5%, respectively. Of
      all patients with an elevated postoperative PTH level at 1 week, 3 months, or 6
      months, only 13.7%, 14.3%, and 14%, respectively, were not cured. CONCLUSIONS:
      Normal postoperative PTH levels reliably predict operative success. However, they
      do not improve upon results predicted by IOPTH levels. Elevated postoperative PTH
      levels do not predict operative failure in most patients. We propose that PTH
      measurements after surgery for pHPT may be misleading, costly, and not indicated
      in normocalcemic patients.

PMID- 17011916
TI  - Should completely intracorporeal anastomosis be considered in obese patients who
      undergo laparoscopic colectomy for benign or malignant disease of the colon?
AB  - BACKGROUND: The outcome of laparoscopic colectomy with completely intracorporeal
      anastomosis (LCIA) in obese and nonobese patients is assessed. METHODS: Forty
      five consecutive patients who underwent LCIA for benign or malignant disease of
      the right and proximal left colon were reviewed prospectively. Obesity was
      defined as a body mass index of >30 kg/m(2). RESULTS: There were 24 men (53%) and
      21 women (47%) with a mean age of 67 years (46-84 years). The mean body mass
      index was 27 kg/m(2) (16-38 kg/m(2)); 13 patients (29%) were obese. One procedure
      was converted to a laparoscopic-assisted colectomy. The mean operative time,
      estimated blood loss, and duration of stay were 218 minutes (110-420 minutes), 82
      mL (50-250 mL), and 5 days (2-11 days), respectively. The mean length of the
      larger incision (extraction site) and the sum of all port incisions was 4 cm (3-8
      cm) and 7 cm (6-10 cm), respectively. Complications occurred in 8 of 45 patients
      (18%), with no deaths. The mean number of harvested lymph nodes per specimen was
      11 (3-30 lymph nodes). Obesity had no effect on operative time (obese patients,
      232 minutes; nonobese patients, 213 minutes), incision length (obese patients, 4
      cm; nonobese patients, 4 cm) estimated blood loss (obese patients, 100 mL;
      nonobese patients, 76 mL), complications (obese patients, 15%; nonobese patients,
      19%), duration of stay (obese patients, 5 days; nonobese patients, 5 days), or
      number of harvested lymph nodes (obese patients, 11 lymph nodes; nonobese
      patients, 11 lymph nodes). There were no port-site hernias or metastases during a
      mean follow-up period of 5 months (1-18 months). CONCLUSIONS: LCIA can offer
      smaller incisions, improved cosmesis, and low conversion rates while oncologic
      principles are preserved. LCIA is a feasible and safe technique with equally
      successful outcomes in thin and obese patients.

PMID- 17011917
TI  - Use of computerized ICU documentation to capture ICU core measures.
AB  - BACKGROUND: Intensive care unit (ICU) core measures that target the prevention of
      catheter-related bloodstream infections (CRBSIs) and ventilator-associated
      pneumonia (VAP) in ventilated ICU patients are underway across the United States.
      Implementation often requires additional personnel to educate providers and
      collect the data. We hypothesized that use of our current computerized ICU
      flowsheet could provide timely, accurate data on ICU core measures without
      additional personnel dedicated to data capture. METHODS: In a 10-bed, closed
      surgical ICU with existing protocols for deep vein thrombosis (DVT) prophylaxis,
      stress ulcer bleeding prophylaxis (SUP), ventilator weaning parameters, and
      glucose control, we created a reporting tool that would document daily weaning
      parameters, head of bed (HOB) at 30 degrees , glucose levels, DVT prophylaxis,
      and SUP. Our glucose protocol targeted <150 mg/dL, with all daily glucose values
      reported rather than just the morning value. The results from the previous 12 am
      to 11:59 pm were available to the rounding team at 7 am. We examined compliance
      at the start and after education of medical staff (March/April for HOB up, DVT,
      and SUP; May/June for glucose control). RESULTS: During 2005, compliance with all
      protocols improved. Percent compliance for DVT prophylaxis, SUP, and HOB up rose
      from as low as 32% at the start of the documentation process to consistently
      higher than the target level of 95%. Compliance for glucose control increased
      after intensive education of nursing and physicians with the mean glucose falling
      from 144 to 122 mg/dL. There was increased nursing workload for checking glucose
      levels in which the mean number of glucose checks rose from a low of 1.5 per
      patient to as high as 8.2 per patient per day. CRBSI and VAP rates did not
      decrease during this period compared with the prior year. Length of stay and
      mortality were unchanged. CONCLUSIONS: Reporting of ICU core measures to treating
      staff can be done accurately and promptly with a computerized system. Education
      was effective in improving compliance levels. No additional personnel were
      required to create reports, capture data, or improve compliance after initial
      development and testing. Although compliance with core measures met target levels
      at the end of the year, we did not observe improved outcomes in terms of CRBSI,
      VAP, mortality, or length of stay.

PMID- 17011918
TI  - Factors associated with failure in managing pelvic sepsis after ileal pouch-anal
      anastomosis (IPAA)--a multivariate analysis.
AB  - BACKGROUND: Pelvic sepsis is known to cause a detrimental outcome after ileal
      pouch-anal anastomosis (IPAA). The aim of this study was to examine potential
      factors associated with failure in managing pelvic sepsis after IPAA. METHODS: We
      performed univariate and multivariate logistic regression analysis on 2518 IPAA
      patients between 1983 and 2005. Failure was defined as pouch failure, the need
      for a permanent ileostomy, or mortality as a result of sepsis. There were 157
      patients (6.2%) with pelvic sepsis after IPAA. These involved anastomotic leak
      34% (54/157) and fistula 25% (40/157). There were 5 mortalities related to
      sepsis. Mean age at surgery was 38.1 +/- 14.4 years and mean follow-up was 5.5 +/
      4.7 years. RESULTS: Pouches were saved in 75.8% patients. Univariate analysis
      identified early sepsis (P = .040), preoperative steroid use (P = .007), and need
      for percutaneous drainage (P = .004) as significant factors associated with
      treatment success. Factors associated with failure were hypertension (P = .026),
      hand-sewn anastomosis (P = .038), associated fistula (P = .0003), need for
      transanal drainage (P = .0002), need for laparotomy to control septic
      complications (P < .0001), delayed ileostomy closure (P = .0003), and need for a
      new diverting ileostomy (P < .0001). By using multivariate analysis with selected
      covariates, significant factors associated with failure were associated fistula
      (P = .0013), need for transanal drainage (P = .003), delayed ileostomy closure (P
      = .022), need for a new ileostomy diversion (P = .004), and hypertension (P =
      .039). We developed a predictive scoring system for failure to use in management
      plans and decision-making for the treatment of septic complications of IPAA.
      CONCLUSIONS: Pelvic sepsis after IPAA has a significant impact on pouch failure.
      This predictive model for failure may play an important role in providing risk
      estimates for successful outcomes.

PMID- 17011919
TI  - The vulnerabilities of age: burns in children and older adults.
AB  - BACKGROUND: Both children and older adults are thought to sustain burns serious
      enough to warrant hospitalization disproportionately more often than other age
      groups, but the incidence, injury characteristics, and outcome have not been
      precisely defined. METHODS: Patients hospitalized with a burn diagnosis were
      identified from hospital discharge data from California, Florida, New Jersey, and
      New York for the 5-year period 2000-2004. RESULTS: In those states, 60,024
      residents were hospitalized with a diagnosis of burn and/or inhalation injury
      according to the International Classification of Diseases, 9th Revision, Clinical
      Modification diagnosis codes. Using population data from the United States Census
      2000, we found that the average annual incidence of hospitalization with a burn
      diagnosis in these 4 states was 155 per million (per M) (95% confidence
      interval,153-158). There were 13,453 children under 15 years of age: incidence,
      163 per M (range, 157-169). Of these 9508 (70%) were under 5 years of age:
      incidence, 363 per M (range, 347-379). In contrast, there were 10,686 patients 65
      years of age or older: incidence, 214 per M (range, 205-224), of whom 2091 were
      at least 85 years old: incidence, 347 per M (range, 314-380). The incidence of
      hospitalization with a burn diagnosis for patients 15 to 64 years of age was 141
      per M (range, 138-145). Compared with children younger than 15 years, patients
      aged 65 years and older more often had flame burns (odds ratio [OR], 2.12), burns
      of 20% or more of body surface area (OR, 2.41), inhalation injury (OR, 2.88),
      respiratory failure (OR, 4.48), and death (OR, 16.53), all P < .0001.
      CONCLUSIONS: Older individuals are the most vulnerable to the morbidity and
      mortality of burn injury. Prevention strategies targeted to those older than 65
      years should be developed.

PMID- 17011920
TI  - Intravenous drug use and HIV: evidence for action now.

PMID- 17011921
TI  - Reducing poverty by investing in young people.

PMID- 17011922
TI  - The challenge facing the NHS is leadership.

PMID- 17011924
TI  - Safe motherhood initiative: 20 years and counting.

PMID- 17011925
TI  - Meeting MDG-5: an impossible dream?

PMID- 17011926
TI  - Japan: are statins still good for everybody?

PMID- 17011927
TI  - Obesity, weight loss, and pregnancy outcomes.

PMID- 17011928
TI  - Medical therapy for urinary stone passage.

PMID- 17011929
TI  - Women's wisdom--a source of knowledge for medicine.

PMID- 17011930
TI  - Mulu Muleta: Ethiopian surgeon working to end fistula.

PMID- 17011931
TI  - Estimating cardiovascular disease risk in diabetes.

PMID- 17011932
TI  - Estimating cardiovascular disease risk in diabetes.

PMID- 17011933
TI  - Estimating cardiovascular disease risk in diabetes.

PMID- 17011936
TI  - Limitation in paediatric logistic organ dysfunction score.

PMID- 17011937
TI  - Overview of randomised trials of ACE inhibitors.

PMID- 17011939
TI  - Malaria and deaths in the English marshes.

PMID- 17011940
TI  - Neutrophils and sepsis.

PMID- 17011941
TI  - Local brain drain.

PMID- 17011942
TI  - Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA
      Study): a prospective randomised controlled trial.
AB  - BACKGROUND: Evidence-based treatment for hypercholesterolaemia in Japan has been
      hindered by the lack of direct evidence in this population. Our aim was to assess
      whether evidence for treatment with statins derived from western populations can
      be extrapolated to the Japanese population. METHODS: In this prospective,
      randomised, open-labelled, blinded study, patients with hypercholesterolaemia
      (total cholesterol 5.69-6.98 mmol/L) and no history of coronary heart disease or
      stroke were randomly assigned diet or diet plus 10-20 mg pravastatin daily. The
      primary endpoint was the first occurrence of coronary heart disease. Statistical
      analyses were done by intention to treat. This trial is registered at
      ClinicalTrials.gov, number NCT00211705. FINDINGS: 3966 patients were randomly
      assigned to the diet group and 3866 to the diet plus pravastatin group. Mean
      follow-up was 5.3 years. At the end of study, 471 and 522 patients had withdrawn,
      died, or been lost to follow-up in the diet and diet plus pravastatin groups,
      respectively. Mean total cholesterol was reduced by 2.1% (from 6.27 mmol/L to
      6.13 mmol/L) and 11.5% (from 6.27 mmol/L to 5.55 mmol/L) and mean LDL cholesterol
      by 3.2% (from 4.05 mmol/L to 3.90 mmol/L) and 18.0% (from 4.05 mmol/L to 3.31
      mmol/L) in the diet and the diet plus pravastatin groups, respectively. Coronary
      heart disease was significantly lower in the diet plus pravastatin group than in
      the diet alone group (66 events vs 101 events; HR 0.67, 95% CI 0.49-0.91;
      p=0.01). There was no difference in the incidence of malignant neoplasms or other
      serious adverse events between the two groups. INTERPRETATION: Treatment with a
      low dose of pravastatin reduces the risk of coronary heart disease in Japan by
      much the same amount as higher doses have shown in Europe and the USA.

PMID- 17011943
TI  - Interpregnancy weight change and risk of adverse pregnancy outcomes: a population
      based study.
AB  - BACKGROUND: Maternal obesity has been positively associated with risk of adverse
      pregnancy outcomes, but evidence of a causal relation is scarce. Causality would
      be lent support if temporal changes in weight affected risk of adverse pregnancy
      outcomes. METHODS: We examined the associations between change in prepregnancy
      body-mass index (BMI) from the first to the second pregnancies, and the risk of
      adverse outcomes during the second pregnancy in a nationwide Swedish study of 151
      025 women who had their first two consecutive singleton births between 1992 and
      2001. FINDINGS: Compared with women whose BMI changed between -1.0 and 0.9 units,
      the adjusted odds ratios for adverse pregnancy outcomes for those who gained 3 or
      more units during an average 2 years were: pre-eclampsia, 1.78 (95% CI 1.52
      2.08); gestational hypertension 1.76 (1.39-2.23); gestational diabetes 2.09 (1.68
      2.61); caesarean delivery 1.32 (1.22-1.44); stillbirth 1.63 (1.20-2.21); and
      large-for-gestational-age birth 1.87 (1.72-2.04). The associations were linearly
      related to the amount of weight change and were also noted in women who had a
      healthy prepregnancy BMI for both pregnancies. INTERPRETATION: These findings
      lend support to a causal relation between being overweight or obese and risks of
      adverse pregnancy outcomes. Additionally they suggest that modest increases in
      BMI before pregnancy could result in perinatal complications, even if a woman
      does not become overweight. Our results provide robust epidemiological evidence
      for advocating weight loss in overweight and obese women who are planning to
      become pregnant and, to prevent weight gain before pregnancy in women with
      healthy BMIs.

PMID- 17011944
TI  - Medical therapy to facilitate urinary stone passage: a meta-analysis.
AB  - BACKGROUND: Medical therapies to ease urinary-stone passage have been reported,
      but are not generally used. If effective, such therapies would increase the
      options for treatment of urinary stones. To assess efficacy, we sought to
      identify and summarise all randomised controlled trials in which calcium-channel
      blockers or alpha blockers were used to treat urinary stone disease. METHODS: We
      searched MEDLINE, Pre-MEDLINE, CINAHL, and EMBASE, as well as scientific meeting
      abstracts, up to July, 2005. All randomised controlled trials in which calcium
      channel blockers or alpha blockers were used to treat ureteral stones were
      eligible for inclusion in our analysis. Data from nine trials (number of
      patients=693) were pooled. The main outcome was the proportion of patients who
      passed stones. We calculated the summary estimate of effect associated with
      medical therapy use using random-effects and fixed-effects models. FINDINGS:
      Patients given calcium-channel blockers or alpha blockers had a 65% (absolute
      risk reduction=0.31 95% CI 0.25-0.38) greater likelihood of stone passage than
      those not given such treatment (pooled risk ratio 1.65; 95% CI 1.45-1.88). The
      pooled risk ratio for alpha blockers was 1.54 (1.29-1.85) and for calcium-channel
      blockers with steroids was 1.90 (1.51-2.40). The proportion of heterogeneity not
      explained by chance alone was 28%. The number needed to treat was 4.
      INTERPRETATION: Although a high-quality randomised trial is necessary to confirm
      its efficacy, our findings suggest that medical therapy is an option for
      facilitation of urinary-stone passage for patients amenable to conservative
      management, potentially obviating the need for surgery.

PMID- 17011945
TI  - Women's groups' perceptions of maternal health issues in rural Malawi.
AB  - BACKGROUND: Improvements in preventive and care-seeking behaviours to reduce
      maternal mortality in rural Africa depend on the knowledge and attitudes of women
      and communities. Surveys have indicated a poor awareness of maternal health
      problems by individual women. We report the perceptions of women's groups to such
      issues in the rural Mchinji district of Malawi. METHODS: Participatory women's
      groups in the Mchinji district identified maternal health problems (172 groups,
      3171 women) and prioritised problems they considered most important (171 groups,
      2833 women). In-depth qualitative data was obtained through six focus-group
      discussions with the women's groups, three with women's group facilitators, and
      four interviews with facilitator supervisors. FINDINGS: The maternal health
      problems most commonly identified by more than half the groups were anaemia
      (87%), malaria (80%), retained placenta (77%), obstructed labour (76%),
      malpresentation (71%), antepartum and postpartum haemorrhage (70% each), and pre
      eclampsia (56%). The five problems prioritised as most important were anaemia
      (sum of rank score 304), malpresentation (295), retained placenta (277),
      obstructed labour (276). and postpartum haemorrhage (275). HIV/AIDS and sepsis
      were identified or prioritised much less because complexity and contextual
      factors hindered their consideration. INTERPRETATION: Rural Malawian women
      meeting in participatory groups showed a developed awareness of maternal health
      problems and the concern and motivation to address them. Community mobilisation
      strategies, such as women's groups, might be effective at reducing maternal
      mortality because they can draw on the collective capacity in communities to
      solve problems and make women's voices heard by decision-makers.

PMID- 17011946
TI  - Maternal mortality: who, when, where, and why.
AB  - The risk of a woman dying as a result of pregnancy or childbirth during her
      lifetime is about one in six in the poorest parts of the world compared with
      about one in 30 000 in Northern Europe. Such a discrepancy poses a huge challenge
      to meeting the fifth Millennium Development Goal to reduce maternal mortality by
      75% between 1990 and 2015. Some developed and transitional countries have managed
      to reduce their maternal mortality during the past 25 years. Few of these,
      however, began with the very high rates that are now estimated for the poorest
      countries-in which further progress is jeopardised by weak health systems,
      continuing high fertility, and poor availability of data. Maternal deaths are
      clustered around labour, delivery, and the immediate postpartum period, with
      obstetric haemorrhage being the main medical cause of death. Local variation can
      be important, with unsafe abortion carrying huge risk in some populations, and
      HIV/AIDS becoming a leading cause of death where HIV-related mortaliy rates are
      high. Inequalities in the risk of maternal death exist everywhere. Targeting of
      interventions to the most vulnerable--rural populations and poor people--is
      essential if substantial progress is to be achieved by 2015.

PMID- 17011947
TI  - Obstetric vesicovaginal fistula as an international public-health problem.
AB  - Vesicovaginal fistula is a devastating injury in which an abnormal opening forms
      between a woman's bladder and vagina, resulting in urinary incontinence. This
      condition is rare in developed countries, but in developing countries it is a
      common complication of childbirth resulting from prolonged obstructed labour.
      Estimates suggest that at least 3 million women in poor countries have unrepaired
      vesicovaginal fistulas, and that 30 000-130 000 new cases develop each year in
      Africa alone. The general public and the world medical community remain largely
      unaware of this problem. In this article I review the pathophysiology of
      vesicovaginal fistula in obstructed labour and describe the effect of this
      condition on the lives of women in developing countries. Policy recommendations
      to combat this problem include enhancing public awareness, raising the priority
      of women's reproductive health for developing countries and aid agencies,
      expanding access to emergency obstetric services, and creation of fistula repair
      centres.

PMID- 17011948
TI  - Complications of obstructed labour: pressure necrosis of neonatal scalp and
      vesicovaginal fistula.

PMID- 17011949
TI  - Long-term outcomes after photorefractive keratectomy.

PMID- 17011951
TI  - Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic
      retinopathy.
AB  - PURPOSE: To report the biologic effect of intravitreal bevacizumab in patients
      with retinal and iris neovascularization secondary to diabetes mellitus. DESIGN:
      Interventional, consecutive, retrospective, case series. PARTICIPANTS: Forty-five
      eyes of 32 patients with retinal and/or iris neovascularization secondary to
      diabetes mellitus. METHODS: Patients received intravitreal bevacizumab (6.2
      microg-1.25 mg). Ophthalmic evaluations included nonstandardized Snellen visual
      acuity (VA), complete ophthalmic examination, fluorescein angiography, and
      optical coherence tomography. MAIN OUTCOME MEASURES: Change in fluorescein
      angiographic leakage of the proliferative diabetic retinopathy (PDR). Secondary
      outcomes included changes in Snellen VA. RESULTS: No significant ocular or
      systemic adverse events were observed. All patients with neovascularization
      demonstrated by fluorescein angiography (44/44 eyes) had complete (or at least
      partial) reduction in leakage of the neovascularization within 1 week after the
      injection. Complete resolution of angiographic leakage of neovascularization of
      the disc was noted in 19 of 26 (73%) eyes, and leakage of iris neovascularization
      completely resolved in 9 of 11 (82%) eyes. The leakage was noted to diminish as
      early as 24 hours after injection. In addition to the reduction in angiographic
      leakage, the neovascularization clinically appeared to involute in many patients
      with a reduction in the caliber or presence of perfused blood vessels. In 2
      cases, a subtle decrease in leakage of retinal or iris neovascularization in the
      fellow uninjected eye was noted, raising the possibility that therapeutic
      systemic levels were achieved after intravitreal injection. Recurrence of
      fluorescein leakage varied. Recurrent leakage was seen as early as 2 weeks in one
      case, whereas in other cases, no recurrent leakage was noted at last follow-up of
      11 weeks. CONCLUSIONS: Short-term results suggest that intravitreal bevacizumab
      is well tolerated and associated with a rapid regression of retinal and iris
      neovascularization secondary to PDR. A consistent biologic effect was noted, even
      with the lowest dose (6.2 microg) tested, supporting proof of concept. The
      observation of a possible therapeutic effect in the fellow eye raises concern
      that systemic side effects are possible in patients undergoing treatment with
      intravitreal bevacizumab (1.25 mg), and lower doses may achieve a therapeutic
      result with less risk of systemic side effects. Further study is indicated.

PMID- 17011952
TI  - A pilot study of multiple intravitreal injections of ranibizumab in patients with
      center-involving clinically significant diabetic macular edema.
AB  - OBJECTIVE: To evaluate the biologic activity of multiple intravitreal injections
      of ranibizumab in patients with center-involving clinically significant diabetic
      macular edema (DME) and to report any associated adverse events. DESIGN: Single
      center, open-label, dose-escalating pilot study. PARTICIPANTS: A total of 10 eyes
      of 10 patients (mean age, 69.3 years [range, 59-81]) with DME involving the
      center of the macula and best-corrected visual acuity (BCVA) in the study eye
      between 20/63 and 20/400. INTERVENTION: Three intravitreal injections of
      ranibizumab (0.3 mg or 0.5 mg each injection) administered on day 0, month 1, and
      month 2, and observation until month 24. MAIN OUTCOME MEASURES: Primary end
      points were the frequency and severity of ocular and systemic adverse events.
      Secondary end points were BCVA and measurement of retinal thickness by optical
      coherence tomography. RESULTS: Of the 10 patients enrolled, 5 received 0.3-mg and
      5 received 0.5-mg ranibizumab. Intravitreal injections of ranibizumab were well
      tolerated. No systemic adverse events were reported. Five occurrences of mild to
      moderate ocular inflammation were reported. At month 3, 4 of 10 patients gained >
      or =15 letters, 5 of 10 gained > or =10 letters, and 8 of 10 gained > or =1
      letters. At month 3, the mean decrease in retinal thickness of the center point
      of the central subfield was 45.3+/-196.3 microm for the low-dose group and
      197.8+/-85.9 microm for the high-dose group. CONCLUSIONS: Ranibizumab appears to
      be a well-tolerated therapy for patients with DME. This pilot study demonstrates
      that ranibizumab therapy has the potential to maintain or improve BCVA and reduce
      retinal thickness in patients with center-involved clinically significant DME.

PMID- 17011953
TI  - Hyperglycemia after repeated periocular dexamethasone injections in patients with
      diabetes.
AB  - PURPOSE: To assess the hyperglycemic effect of 3 consecutive daily periocular
      steroid injections in patients with diabetes. DESIGN: Retrospective observational
      study in a national eye center. PARTICIPANTS: Twenty-five hospitalized patients
      with type 2 diabetes who received a subconjunctival (n = 11) or a peribulbar
      injection (n = 14) with 4 mg dexamethasone disodium phosphate once a day for 3
      consecutive days for ocular conditions. METHODS: Baseline patient characteristics
      were recorded as well as serial blood glucose measurements and hypoglycemic
      interventions, both performed according to a written protocol. MAIN OUTCOME
      MEASURES: Serial blood glucose measurements and hypoglycemic interventions.
      RESULTS: Each ocular injection with dexamethasone was followed around 6 hours
      later by an increase of blood glucose up to a median doubling from baseline
      (+100% increase) followed by falls until the next injection, toward a median 13%
      increase from baseline before the next ocular injection. Older age (P<0.05),
      duration of diabetes (P = 0.01), and microangiopathy or macroangiopathy (P =
      0.01) were associated with higher blood glucose rises. Using a 14-mmol/l
      threshold for intervention, the probability of requiring additional hypoglycemic
      treatment during ocular steroid therapy in patients with HbA1c >7.5% and up to
      7.5% was 100% and 60%, respectively. CONCLUSIONS: Periocular injections with
      dexamethasone in patients with type 2 diabetes induce a marked hyperglycemic
      effect, similar to that observed during intravenous pulse methylprednisolone.

PMID- 17011954
TI  - Surgical management of pseudophakic retinal detachments: a meta-analysis.
AB  - PURPOSE: To compare the success of pars plana vitrectomy (PPV) versus scleral
      buckle (SB) in the management of uncomplicated pseudophakic retinal detachments
      (RDs). DESIGN: Meta-analysis of published studies from 1966 to 2004 regarding
      surgical treatment of pseudophakic RDs. PARTICIPANTS: Two thousand two hundred
      thirty eyes: 1579 operated by SB, 457 by PPV, and 194 by the combined method of
      PPV and SB. METHODS: We compared reattachment and functional success rates after
      3 commonly practiced surgical interventions for pseudophakic RDs: PPV, SB, and
      the combined method. Twelve hundred thirty-two articles were retrieved from
      Medline and by cross-reference searches. Articles with sufficient data on
      preoperative evaluation, applied surgical technique, and anatomical and
      functional success rates were included in this analysis. Articles regarding
      complex pseudophakic RDs, treatment by laser or pneumatic retinopexy, studies
      with indistinguishable treatment outcomes from phakic and pseudophakic RDs, or
      reviews without original data were excluded. MAIN OUTCOME MEASURES: Anatomical
      success rates after initial surgical intervention and after reoperation(s) for
      primary failures, and best or final visual outcome at the end of follow-up.
      RESULTS: Of 1232 papers, 29 matched inclusion criteria. After controlling for
      variation between study characteristics, PPV and the combined method resulted in
      higher initial reattachment rates (odds ratio [OR], 1.69; 95% confidence interval
      [CI], 1.07-2.68, and OR, 3.54; 95% CI, 1.57-7.97, respectively) as compared with
      SB. The differences between the procedures persisted for final reattachment
      outcome despite reoperation for primary failures. Final visual outcome also was
      found to depend on the choice of primary surgical intervention. After controlling
      for differences in the study characteristics, the probability of visual
      improvement was higher after PPV (OR, 2.34; 95% CI, 1.58-3.46) or the combined
      method (OR, 11.52; 95% CI, 4.42-30.04) as compared with SB. CONCLUSIONS: A meta
      analysis of published literature implies that PPV with or without SB is more
      likely to achieve a favorable anatomical and visual outcome than conventional SB
      alone in uncomplicated pseudophakic RDs. However, the inherent limitations of
      differing study protocols, quality of included studies, and publication bias in a
      pooled analysis should be recognized.

PMID- 17011955
TI  - Visual recovery after scleral buckling procedure for retinal detachment.
AB  - PURPOSE: To evaluate prognostic factors for visual and anatomic outcomes,
      including complications after scleral buckling procedure (SBP) for primary
      rhegmatogenous retinal detachments. DESIGN: Retrospective, consecutive,
      nonrandomized, comparative interventional case series. PARTICIPANTS: Patients
      undergoing SBP for primary rhegmatogenous retinal detachment performed by a
      single surgeon. METHODS: The patients' medical records were reviewed.
      Preoperative and intraoperative factors analyzed for their association with
      visual acuity and anatomic outcomes included macular detachment, duration of
      macular detachment, preoperative visual acuity, lens status, refractive error,
      extent of detachment, number of breaks, internal gas tamponade, and drainage of
      the subretinal fluid. Secondary outcomes included frequency of further surgery,
      complications, and fellow eye retinal detachment. The fellow eye of the patients
      was excluded from consideration of prognostic factors. MAIN OUTCOME MEASURES:
      Best-corrected visual acuity at 2 months and at final follow-up examination as
      well as anatomic factors including retinal reattachment at 1 day, 2 months, and
      last follow-up examination. RESULTS: There were 672 patients studied, including
      457 (68%) with macular detachment. The use of gas, drainage of subretinal fluid,
      and lens status did not influence final anatomic or visual results. Macular
      detachment was the most important prognostic factor for anatomic (P = 0.031) and
      visual acuity success (P<0.001). Better preoperative visual acuity (P<0.001),
      fewer quadrants involved by the detachment (P<0.001), and lack of high myopia (P
      = 0.001) were important positive prognostic factors for visual acuity. The
      duration of macular detachment was not of prognostic value up to 30 days'
      duration. CONCLUSIONS: Visual recovery after retinal reattachment was most
      dependent on macular involvement. Duration of macular detachment had surprisingly
      little influence on postoperative visual acuity.

PMID- 17011956
TI  - The RPS adeno detector for diagnosing adenoviral conjunctivitis.
AB  - PURPOSE: To compare the sensitivity, specificity, and accuracy of the RPS Adeno
      Detector (Rapid Pathogen Screening Inc., South Williamsport, PA) against both
      viral cell culture with confirmatory immunofluorescence staining (CC-IFA) and the
      polymerase chain reaction (PCR) for diagnosing adenoviral conjunctivitis. DESIGN:
      Prospective, nonrandomized, masked, multicenter clinical trial. PARTICIPANTS: One
      hundred eighty-six consecutive patients from 5 clinical centers seeking treatment
      within 1 week of developing a red eye and thought to have acute conjunctivitis.
      METHODS: The RPS Adeno Detector is a 10-minute in-office lateral flow
      immunoassay. Patients were tested with the RPS Adeno Detector, CC-IFA, and PCR to
      detect the presence of adenovirus. MAIN OUTCOME MEASURES: The sensitivity,
      specificity, and accuracy of the RPS Adeno Detector were assessed for identifying
      cases of adenoviral conjunctivitis. RESULTS: Compared with CC-IFA, the RPS Adeno
      Detector was 88% sensitive and 91% specific at detecting adenoviral
      conjunctivitis. Using PCR as a reference method, the sensitivity of the RPS Adeno
      Detector increased to 89% and the specificity increased to 94%. Compared with
      PCR, CC-IFA was found to be 91% as sensitive and 100% as specific. CONCLUSIONS:
      The RPS Adeno Detector demonstrated sufficient sensitivity and specificity to be
      used in the physician's office for the detection of adenoviral conjunctivitis.

PMID- 17011957
TI  - Recessive cornea plana in the Kingdom of Saudi Arabia.
AB  - OBJECTIVE: To characterize the molecular genetics of clinically diagnosed
      recessive cornea plana in the Kingdom of Saudi Arabia and establish the presence
      of common or limited founders (ancestors who originally harbored the disease
      causing mutation) in the country's historically isolated population. DESIGN:
      Prospective interventional case series. PARTICIPANTS: Twelve affected patients
      from apparently unrelated Saudi Arabian nuclear families with clinically
      diagnosed recessive cornea plana. METHODS: Clinical ophthalmic examination and
      venous blood sampling for DNA sequencing. MAIN OUTCOME MEASURES: Age, gender,
      keratometry, best-corrected visual acuity, ocular alignment, cycloplegic
      refraction, significant findings of a complete ophthalmic examination, and
      keratocan gene (KERA) haplotype analysis. RESULTS: All 12 individuals had classic
      phenotypic features of recessive cornea plana and were homozygous for 1 of 2 KERA
      mutations--a novel frameshift mutation (1634delC) or a previously reported
      nonsense mutation (R313X). Haplotype analysis was consistent with a separate
      distinct common founder effect for each instance. An additional Saudi KERA
      mutation (R279X) has been reported previously in one family. CONCLUSION: Specific
      for mutation in KERA, the ophthalmic phenotype of recessive cornea plana does not
      significantly vary with different KERA mutations. The occurrence of a rare
      inherited disease in a historically isolated population is not always due to a
      single common founder effect; it may be explained by cultural preferences such as
      consanguinity (intrafamilial marriage) and endogamy (intratribal marriage), which
      enhance expression of recessively inherited diseases.

PMID- 17011958
TI  - Effects of ablation diameter on long-term refractive stability and corneal
      transparency after photorefractive keratectomy.
AB  - OBJECTIVE: To evaluate the effects of ablation diameter on long-term refractive
      stability and corneal transparency after photorefractive keratectomy (PRK).
      DESIGN: Long-term, prospective, follow-up study. PARTICIPANTS: One hundred twenty
      three eyes treated between 1990 and 1993 at one institution as part of a number
      of ethical committee-approved clinical studies underwent long-term follow-up at
      10 to 12 years after PRK. INTERVENTION: Photorefractive keratectomy was performed
      using the Summit Technology UV 200 and OmniMed Excimer lasers with either 4.0-mm
      (n = 36), 5.0-mm (n = 47), or 6.0-mm (n = 40) optical zones and either -3.0
      diopters (D) or -6.0-D myopic spherical corrections, based on the original
      Munnerlyn algorithms. MAIN OUTCOME MEASURES: Refractive stability, refractive
      predictability, best spectacle-corrected visual acuity, and corneal haze.
      RESULTS: Refractive outcome at 1 and 10 to 12 years of follow-up was better with
      6.0-mm treatments, especially for -6.0-D corrections (P>0.001). The early
      hyperopic shift was significantly reduced with 6.0-mm zones, with less regression
      between 1 and 6 months, compared with 5.0- and 4.00-mm PRK, especially for -6.0-D
      corrections (P<0.001). The postoperative refraction remained stable between 1 and
      10 to 12 years in all groups. Objective measurements of haze were less with 6.0
      mm compared with 4.0- and 5.0-mm treatments (P<0.001). Night vision problems were
      significantly less with 6.0-mm PRK (P<0.01). There was no evidence of progressive
      hyperopic shift, corneal ectasia, or late onset of corneal haze in any of the
      eyes during the follow-up period. CONCLUSIONS: Refractive stability was
      maintained between 1 year and 10 to 12 years after PRK with 4.0-, 5.0-, and 6.0
      mm optical zones. A significant linear trend was observed in terms of refractive
      predictability, early hyperopic shift, regression, corneal transparency, and
      night haloes with better outcomes in PRK with a larger ablation zone. None of the
      eyes had sight-threatening complications such as ectasia or late-onset corneal
      haze during the follow-up.

PMID- 17011959
TI  - Biaxial microincision versus coaxial small-incision clear cornea cataract
      surgery.
AB  - OBJECTIVE: To compare clinical outcomes of biaxial microincision (1.5 mm) and
      coaxial small-incision (2.75 mm) clear cornea cataract surgery. DESIGN:
      Randomized controlled clinical trial. PARTICIPANTS: Seventy eyes of 70 patients
      were examined at a German university eye hospital. INTERVENTION: The 70 patients
      (70 eyes) were assigned randomly (1:1) to a biaxial or conventional coaxial
      incision group. Both groups underwent phacoemulsification using pulsed ultrasound
      energy with variable duty cycles, followed by microincision intraocular lens
      implantation. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA),
      astigmatism, laser flare photometry value, effective phacoemulsification time
      (EPT), and endothelial cell count were evaluated. RESULTS: The treatment groups
      did not differ in baseline characteristics (median BCVA of 20/40 preoperatively
      in both groups, P = 0.97). On postoperative day 1, BCVA was better in the biaxial
      group than in the coaxial group (20/25 vs. 20/33, P = 0.018). Eight weeks after
      surgery, median BCVAs were 20/20 in the biaxial group and 20/25 in the coaxial
      group (P = 0.015). Median changes in astigmatism were -0.15 diopters (D) in the
      biaxial group and -0.31 D in the coaxial group. Neither clinically relevant nor
      statistically significant differences were found in laser flare photometry
      values. Effective phacoemulsification time was >3 seconds in only 34% of biaxial
      procedures, versus 68% of coaxial procedures (P = 0.013). At 8 weeks after
      surgery, endothelial cell counts were decreased similarly in the biaxial (14.5%)
      and coaxial (14.1%) groups (P = 0.408). CONCLUSIONS: With the biaxial
      microincision technique, EPT is shorter and BCVA improves more rapidly, with no
      difference in astigmatism, laser flare photometry results, or endothelial cell
      count relative to the coaxial small-incision technique for phacoemulsification.

PMID- 17011960
TI  - Are disposable prisms an adequate alternative to standard Goldmann tonometry
      prisms in glaucoma patients?
AB  - PURPOSE: To evaluate the accuracy and reliability of 2 single-use tonometry
      devices (Tonosafe and Tonojet) as an alternative to standard Goldmann prisms in
      patients attending dedicated glaucoma clinics. DESIGN: Prospective experimental
      study with human subjects. PARTICIPANTS: Two hundred forty glaucoma patients who
      attended 2 glaucoma clinics at the Stepping Hill Hospital between January and
      February 2005. METHODS: During each examination, intraocular pressure (IOP) was
      measured 3 times, using the standard Goldmann prism, Tonosafe, and Tonojet,
      respectively. The prism sequence was predetermined at random using a computer,
      and the measurements were taken at 5-minute intervals. Data were analyzed using
      the Bland-Altman method of differences. MAIN OUTCOME MEASURE: Intraocular
      pressure. RESULTS: Intraocular pressure ranged from 6 to 68 mmHg. Linear
      regression analysis indicated that there was a proportional bias between Goldmann
      and Tonosafe (r2 = 0.368, P<.001), especially for values higher than 25 mmHg. On
      the other hand, there was no statistically significant proportional bias between
      Goldmann and Tonojet (r2 = 0.006, P = 0.14). CONCLUSIONS: Caution should be
      exercised when using Tonosafe prisms in the presence of IOP higher than 25 mmHg.
      On the other hand, Tonojet is an adequate and useful alternative to the Goldman
      tonometer for glaucoma patients.

PMID- 17011961
TI  - Utilization, appropriate care, and quality of life for patients with cataracts:
      American Academy of Ophthalmology, American Society of Cataract and Refractive
      Surgery, and European Society of Cataract and Refractive Surgeons.

PMID- 17011962
TI  - Cataract surgery in patients with Fuchs'.

PMID- 17011963
TI  - LASEK versus PRK.

PMID- 17011964
TI  - Phacoemulsification vs. manual small-incision cataract surgery.

PMID- 17011965
TI  - Intraoperative floppy iris syndrome.

PMID- 17011968
TI  - Visual Sensations during Vitrectomy.

PMID- 17011969
TI  - Local anesthesia for vitrectomy.

PMID- 17011970
TI  - Apolipoprotein E gene and macular degeneration.

PMID- 17011972
TI  - Approaches for correcting aponeurotic ptosis.

PMID- 17011974
TI  - Eyelid infection.

PMID- 17011976
TI  - Ophthalmic clinical evaluation exercise.

PMID- 17011977
TI  - Deletion size characterization of der(9) deletions in Philadelphia-positive
      chronic myeloid leukemia.
AB  - About 95% of the CML patients with chronic myeloid leukemia (CML) have a
      Philadelphia chromosome resulting from a reciprocal translocation between bands
      9q34 and 22q11.2 that juxtaposes the 3' region of the ABL gene to the 5' region
      of BCR. Over the past few years, submicroscopic deletions due to the loss of
      sequences proximal to chromosome 9 breakpoint or distal to chromosome 22
      breakpoint have been found using fluorescence in situ hybridization (FISH). Among
      150 CML bone marrow samples analyzed by molecular cytogenetics in our laboratory,
      11 had a der(9) deletion detectable by FISH (deletion of the 5'ABL region and
      3'BCR region in 10 samples and deletion of the 5'ABL region solely in 1 sample).
      To delineate the size of the deletions, FISH mapping was performed using 22
      bacterial artificial chromosomes (BACs), 11 on either side of the breakpoints,
      the mean distance between BACs being 0.5 Mb. The deletion size of the 5'ABL
      region on the der(9) extended from 2 to 5 Mb, the minimal deletion size being
      localized between BACs RP11-101E3 and RP11-83J21. In two patients, the deletion
      size of the 3'BCR region was about 500 kb (between RP11-80O7 and RP11-681C06).
      The poor prognosis associated with these deletions was postulated by several
      workers to be explained by haploinsufficiency of a tumor suppressor gene.
      However, in our cases, the hypothetical deletion of one or more tumor suppressor
      genes is not sufficient to explain the poor response to interferon therapy, but
      the good response to imatinib treatment. We think that there could be one or more
      genes coding for interferon receptors or for proteins acting directly or
      indirectly with these receptors in the deleted regions.

PMID- 17011978
TI  - RNA-based analysis of BRCA1 and BRCA2 gene alterations.
AB  - Alterations in BRCA1 and BRCA2 genes account for a large proportion of hereditary
      breast and ovarian cancers. Mutations and variants of unknown pathological
      significance have been identified in both genes; however, most of them have been
      studied only at the genomic level, and their effect on mRNA expression remains
      unknown. We identified two BRCA1 and six BRCA2 splice site variants, and one
      BRCA2 alteration at exon 14. Our aim was to ascertain the effect on RNA
      processing of the variants still unclassified. We found that BRCA1 c.IVS11 +
      1G>A, BRCA2 c.7252_7272delinsTG, BRCA2 c.IVS2 + 1G>A, BRCA2 c.IVS13-2A>G, BRCA2
      c.IVS21 + 4A>G, and BRCA2 c.9345G>A lead to aberrant transcripts in lymphocytes.
      Five of these six splice site variants caused a complete inactivation of the
      mutant allele because they produced frameshift similar to previously described
      deleterious exonic variants. Therefore, we consider them to be true deleterious
      mutations, possibly associated with an increased lifetime risk of breast or
      ovarian cancer. BRCA1 c.IVS17 + 6C>G, BRCA2 c.IVS12-9del4, and BRCA2 IVS1-9del3
      represent rare variants, not disrupting normal mRNA processing. The last two
      BRCA2 genetic variants had not been reported in the Breast Cancer Information
      Core BIC database.

PMID- 17011979
TI  - Identification of chromosome aberrations in esophageal cancer cell line KYSE180
      by multicolor fluorescence in situ hybridization.
AB  - Analysis of chromosomal changes in esophageal squamous cell carcinoma (ESCC) can
      illuminate the molecular mechanisms underlying the development and progression of
      this cancer, which is among the 10 most common malignant tumors. Cell lines are
      better suited than surgical samples for chromosome analysis in this cancer. This
      study used multicolor fluorescence in situ hybridization (M-FISH) to characterize
      the molecular cytogenetics of ESCC in cell line KYSE180. Two pools of 12-color
      whole-chromosome painting probes were designed, and two rounds of FISH were
      performed on the same metaphase spreads. Loss of DNA copy number was observed at
      4p, 5q, 6q, 9, 10p, 12p, 13, 14p, 15p, 18p, 18q, 20, 22, and Y. Chromosomal gains
      and translocations occurred at the entire or part of 1, 2p, 3, 4p, 5p, 5q, 6p, 7,
      8, 10q, 11, 12q, 14q, 16, 17q, 19, and Xp. Seven derivative chromosomes (5, 8,
      12, 14, 14, 14, and 17) presented complex translocations, each involving three or
      four chromosomes. No chromosomes 9, 13, or Y were detected. These results add
      significant information to the existing karyotype description of KYSE180 and
      provide detailed cytogenetic background data for appropriate use of the cell
      line.

PMID- 17011980
TI  - Effects of cyclin D1 (CCND1) polymorphism on susceptibility to lung cancer in a
      North Indian population.
AB  - Cyclin D1 is involved in normal regulation of the cell cycle and plays an
      important role in the transition from G1 to S phase of the cell cycle. The CCND1
      gene has a G-->A polymorphism in exon 4 that increases the frequency of alternate
      splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung
      cancer patients (n = 151) and in a matched control population (n = 151). DNA was
      isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase
      chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were
      analyzed by means of agarose gel electrophoresis. The data obtained were analyzed
      using multiple logistic regression. After adjustment for age, sex, and smoking
      status, the AG genotype was associated with an increased risk for overall lung
      cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92-3.14). No
      association was found between AA genotype and risk of lung cancer. In smokers,
      the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95%
      CI = 1.03-3.71, P = 0.03). No positive association was found between CCND1
      genotypes in nonsmokers. The results suggest that the CCND1 A870G gene
      polymorphisms may increase the risk of lung cancer in smokers from north India.

PMID- 17011981
TI  - Fluorescence in situ hybridization studies using BAC clones of the EVI1 locus in
      hematological malignancies with 3q rearrangements.
AB  - Chromosomal rearrangements involving 3q26 are a recurrent aberration in malignant
      myeloid disorders. Several of these rearrangements involve the EVI1 oncogene or
      its surrounding sequences and are associated with a poor prognosis. Fluorescence
      in situ hybridization (FISH) studies using bacterial artificial chromosome (BAC)
      clones were conducted to determine whether the EVI1 locus was rearranged in nine
      patients with hematological malignancies carrying 3q abnormalities. A dual-color
      probe was constructed with nine BACs; centromeric clones covering 1 Mb and
      including the EVI1 gene were labeled with a red fluorescent dye and telomeric
      clones covering 1 Mb were labeled with a green fluorescent dye. Two patients
      showed normal copies of the EVI1 locus, four patients showed one EVI1 locus
      rearranged (in all of them the breakpoint on 3q26 was telomeric to EVI1), one
      patient showed one copy of the EVI1 locus translocated to another chromosome, one
      patient showed one copy of the EVI1 locus rearranged and the other copy
      translocated, and one patient showed one extra copy of the EVI1 locus. In four
      cases, FISH studies using the EVI1 clones detected different 3q abnormalities not
      previously found by conventional cytogenetics. FISH analysis with BAC clones was
      a useful tool for identifying the chromosome breakpoints affecting the EVI1 locus
      in patients with 3q26 rearrangements.

PMID- 17011982
TI  - Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal
      cancer in a Chinese population.
AB  - Epidemiologic, structural, and bioinformatic analyses were used to evaluate
      variants in the MSH2 and MLH1 genes in 187 subjects with suspected hereditary
      gastrointestinal cancer in China. An increased frequency of variants was observed
      in exon 7 of the MSH2 gene; there was a statistical difference (P < 0.05) between
      the colorectal cancer (CRC) group (6/82, or 7.32%) or the gastric cancer (GC)
      group (8/105, or 7.62%) and the controls (1/112, or 0.89%). The odds ratio (OR)
      was 8.76 for CRC and 9.15 for GC, suggesting an association between the presence
      of variants in exon 7 of the MSH2 gene and risk of gastrointestinal cancer in the
      studied population. In addition, MSH2 1168T showed trends toward association with
      CRC and GC in young (<50 yr) sporadic disease patients (OR = 10.97 and 17.15,
      respectively). The c.1168C>T (p.Leu390Phe), c.1255C>A (p.Gln419Lys), and
      c.1261C>A (p.Leu421Met) in exon 7 and c.518T>G (p.Leu173Arg) in exon 3 of MSH2
      were suspected as predisposing to gastrointestinal cancer. Variants c.505A>G
      (p.Ile169Val), c.1221C>G (p.Leu407Leu) and c.1223A>G (p.Tyr408Cys) in MSH2 and
      c.655 A>G (p.Ile219 Val) and c.927C>T (p.Pro309Pro) in MLH1 might be merely
      polymorphisms. Consequences of the variant c.2101C>A (p.Gln701Lys) in MLH1 remain
      to be elucidated.

PMID- 17011983
TI  - Unusual complex hyperdiploid karyotypes in myelodysplastic syndromes.
AB  - Over an 18-year period, 10 myelodysplastic syndrome (MDS) patients with complex
      hyperdiploid karyotypes were identified. According to the FAB classification, the
      10 patients were subclassified as three refractory anemias (RA), three refractory
      anemias with excess blasts (RAEB), two RAEB in transformation (RAEB-t), and two
      unclassified MDS. According to the WHO classification, the diagnoses were two RA,
      one refractory cytopenia with multilineage dysplasia, two RAEB-1, one RAEB-2, two
      unclassified MDS, and two acute myeloid leukemia. Six were secondary MDS. Four
      patients showed marked dyserythropoiesis; three of these were secondary MDS. The
      chromosome number ranged from 47 to 62, and clonal evolution or composite
      karyotypes were noted in 7 patients. Seven patients had at least one clone with
      >50 chromosomes. Recurrent defects included chromosome 5, 17, and 13
      abnormalities. Notably, trisomy 8 and monosomy 7 were rare in that group of
      patients. Three of four patients with marked dyserythropoiesis shared
      abnormalities of both chromosomes 13 and 17.

PMID- 17011984
TI  - Characterizing genetically stable and unstable gastric cancers by microsatellites
      and array comparative genomic hybridization.
AB  - Gastric cancer (GCA) displays a variety of genomic aberrations, including DNA
      copy number alterations, microsatellite instability (MSI), and loss of
      heterozygosity (LOH). The main aim of the present work was to determine the copy
      number aberrations in tumors with and without MSI or LOH. Fifteen fresh-frozen
      GCA samples, 11 of the intestinal and 4 of the diffuse type, were grouped by
      microsatellite analysis into high-level MSI (MSI-H, n = 2), LOH (n = 5), and
      microsatellite stable, LOH not detected (MSS/LOH-N, n = 8) tumors. The DNA
      samples were subsequently analyzed by array comparative genomic hybridization
      with 16,000 cDNA clones. As expected, the LOH tumors showed more copy number
      changes; however, the frequency of small-size amplifications was similar across
      all tumor groups. In addition, the cDNA arrays detected two apparently single
      gene amplicons, at 11q13 (CCND1) and 12p12.1 (K-RAS), the presence of which were
      confirmed using oligonucleotide arrays. A novel amplicon at 5q13.2 was found only
      in diffuse-type tumors, which were otherwise genetically stable. The results
      suggest that DNA copy number changes may also occur in gastric cancers that show
      genomic stability in microsatellite analysis.

PMID- 17011985
TI  - Serial cytogenetic alterations resulting in transformation of a low-grade
      follicular lymphoma to Burkitt lymphoma.
AB  - Follicular lymphoma (FL) is the most common indolent or low-grade non-Hodgkin
      lymphoma (NHL). Histologic transformation to high-grade lymphoma, generally to
      diffuse large B-cell lymphoma, occurs in 25-35% of cases. Although t(14;18), the
      cytogenetic hallmark of FL, has been found in approximately 85% of these cases,
      multiple secondary cytogenetic and molecular genetic changes underlie the
      transformation process. We report the case of a 58-year-old patient who presented
      with stage IVA, grade 2 FL that subsequently transformed to Burkitt lymphoma.
      Multiple chromosomal aberrations, including three novel translocations, were
      observed related to this transformation. Inversion (1)(p36.3q12) and
      t(3;14;18)(p23;q32;q21) occurred prior to transformation and may have contributed
      to the transformation process. A t(1;11)(q25;q13) was acquired simultaneously
      with t(8;22) and, in conjunction with other chromosomal abnormalities, coincided
      with an extremely aggressive clinical course. The frequent breakage of 1q
      observed in this case suggests that the region harbors important genomic signals
      for the transformation of FL.

PMID- 17011986
TI  - Genetic expression profiles and chromosomal alterations in sporadic breast cancer
      in Mexican women.
AB  - Breast cancer is the second-leading cause of death among Mexican women >35 years
      of age. At the molecular level, changes in many genetic pathways have been
      reported to be associated with this neoplasm. To analyze these changes, we
      determined gene expression profiles and chromosomal structural alterations in
      tumors from Mexican women. We obtained mRNA to identify expression profiles with
      microarray technology, and DNA to determine amplifications and deletions, in 10
      fresh sporadic breast tumor biopsies without treatment, as well as in 10
      nonaffected breast tissues. Expression profiles were compared with genetic
      changes observed by comparative genomic hybridization (CGH). We compared the
      expression profiles against the structural alterations from the studied genes by
      means of microarrays; at least 17 of these genes correlated with DNA copy number
      alterations. We found that the following genes were overexpressed: LAMC1, PCTK3,
      CCNC, CCND1, FGF3, PCTK2, L1CAM, BGN, and PLXNB3 (alias PLEXR). Underexpressed
      genes included CASP9, FGR, TP73, HSPG2, and ERCC1; genes turned off included
      FRAP1, EPHA2 (previously ECK), IL12A, E2F5, TNFRSF10B, TNFRSF10A, EFNB3, and
      BCL2. The results will allow us, in the near future, to outline genes that could
      serve as diagnostic, prognostic, or target therapy markers for the Mexican
      population.

PMID- 17011987
TI  - Coexistence of neocentromeric marker 3q and trisomy 3 in two different tissues in
      a 3-year-old boy with peripheral T-cell lymphoma: support for a gene dosage
      effect hypothesis.
AB  - A very small supernumerary de novo marker chromosome was ascertained during
      cytogenetic diagnosis of a 3 1/2-year-old boy with peripheral T-cell lymphoma,
      unspecified. The marker, which was C-band and alpha-satellite DNA negative, was
      identified in the pleural effusion and involved cervical lymph node whereas the
      involved bone marrow cells had trisomy 3 as a clone. The neocentromere marker was
      characterized by multiple probes demonstrating an inversion duplication of the
      distal portion of chromosome 3q involving the BCL6 gene. Whole or partial trisomy
      3q represents one of the most recurrent chromosomal abnormalities occurring in T
      cell lymphomas, suggesting that the 3q contains a critical region for the
      pathogenesis of T-cell lymphoma. Our present case showed that the critical region
      may reside within the neocentromere marker 3q27~q29 in this case in particular
      and revealed a different mechanism in increasing gene dosage rather than gene
      disruption. In addition, this type of neocentromere is one most often reported in
      constitutional cases. Here, we report its presence in cancer for the first time.

PMID- 17011988
TI  - Primary mediastinal (thymic) large B-cell lymphoma with a der(14)t(8;14)(q24;q32)
      and a translocation of MYC to the derivative chromosome 14 with a deleted IgH
      locus.
AB  - We report a case of primary mediastinal (thymic) large B-cell lymphoma (PMBL)
      with an initial karyotype containing numerical chromosomal aberrations: +X, +9,
      +12, +21, and a novel translocation t(2;11)(q?31; q23 approximately 24) with a
      duplication of the derivative chromosome 11. Subsequent multicolor fluorescence
      in situ hybridization (M-FISH) analysis revealed a der(14)t(8;14)(q24;q32).
      Further analysis using fluorescence in situ hybridization (FISH) with locus
      specific probes revealed loss of the entire IgH locus from the der(14)t(8;14) and
      relocation of MYC to this derivative chromosome 14. Our data show definitively
      the existence of the t(8;14) in PMBL, previously only suspected. This finding
      supplies additional evidence that a translocation-mediated MYC activation may be
      an important event in the pathogenesis of this unique lymphoma.

PMID- 17011989
TI  - A (9;11)(q34;q13) translocation in a hibernoma.
AB  - The diagnosis of hibernoma has historically been made by histopathologic
      examination and finding of characteristic brown fat cells with granular
      multivacuolated cytoplasm. The diagnosis of hibernoma may be complicated,
      however, because seemingly diagnostic cells could be mistakenly identified as
      lipoblasts, leading to the erroneous diagnosis of well-differentiated
      liposarcoma. Cytogenetic alterations in lipomatous tumors are well established
      and could be used for diagnostic purposes. Previous cytogenetic abnormalities
      reported in hibernomas have included alteration of 11q13 region. Here, we present
      a case of a hibernoma with a novel cytogenetic alteration involving a reciprocal
      translocation between 9q and 11q that was useful in establishing the final
      diagnosis.

PMID- 17011990
TI  - Cytogenetic and morphological findings in 166 patients with de novo acute myeloid
      leukemia in southern Brazil.
AB  - Chromosomal rearrangements correlate with different clinical subgroups of blood
      disorders. Some of these chromosomal abnormalities are found in individuals from
      specific geographical areas and ethnic groups. A high incidence of t(15;17)
      translocation has been observed, for example, in the Hispanic populations of the
      United States and Spain. The same occurs in South America, due to the rich
      diversity of ethnic groups that colonized the region. We performed a cytogenetic
      analysis of 166 patients at the Division of Hematology of Hospital de Clinicas de
      Porto Alegre between 1990 and 2002. Those patients who met the criteria for de
      novo acute myeloid leukemia (AML) and whose karyotypes could be successfully
      determined were included in the study. The karyotypes of each patient and the
      French-American-British (FAB) criteria for the diagnosis of AML were reviewed.
      Chromosomal abnormalities were identified and classified according to ISCN 1995.
      Chromosomal abnormalities were found in 53.6% of cases. Abnormalities were
      significantly more common in the FAB-M3 group (70.3%). The most common balanced
      translocation was t(15;17), observed in 13.25% of the patients.

PMID- 17011991
TI  - High-level amplification of the RUNX1 gene in two cases of childhood acute
      lymphoblastic leukemia.
AB  - The RUNX1 (alias AML1) gene is involved in several patterns of chromosomal
      translocations and rearrangements associated with human acute leukemia. Often,
      multiple signals for AML1 have been observed in childhood acute lymphoblastic
      leukemia (ALL) due to frequent polysomy of chromosome 21 in this leukemia.
      Additionally, high-level amplification of AML1, in the absence of polysomy of
      chromosome 21, has been reported in childhood ALL. We report two new cases of
      childhood ALL, without a ETV6/RUNX1 (alias TEL/AML1) rearrangement, showing high
      level amplification of the AML1 gene detected by fluorescence in situ
      hybridization and comparative genomic hybridization analysis. The first case was
      an 11-year-old girl with 7-12 signals for AML1 in nearly 84% of the cells, and
      the loss of a TEL allele. In the second patient, a 6-year-old girl, multiple
      copies of the AML1 gene were also observed in 99% of the cells, although no
      deletion of TEL was found. The similarity in the clinicobiologic features of all
      the cases with this abnormality points to an emerging molecular cytogenetic
      subgroup of B-cell precursor ALL and suggests a possible dosage effect of AML1 in
      the pathogenesis of leukemia.

PMID- 17011992
TI  - Cytogenetics of pineoblastoma: four new cases and a literature review.
AB  - Pineoblastoma represents a class of primitive neuroectodermal tumors (PNET) with
      poorly differentiated neuroepithelial cells that are histologically
      indistinguishable from medulloblastomas. It is a rare tumor, typically arising in
      childhood, and to date only a few cytogenetic cases have been published. We
      report four new cases in which conventional cytogenetics demonstrated the
      presence of an abnormal clone. The tumors showed a variety of ploidy levels, from
      hypodiploid to hypertetraploid. Both structural and numerical aberrations were
      frequent, and in three out of the four cases a large degree of cell-to-cell
      variation was observed. The most frequently involved chromosome in structural
      rearrangements was chromosome 1, observed in three of the four cases. The short
      arm was involved in two of the three cases; in the third case, the anomaly was in
      the long arm. Two cases showed unbalanced gain of chromosome 17q, one of them
      showing i(17)(q10). Together, the four cases illustrate the complex karyotypic
      nature of this tumor type and represent a step toward determining whether a
      nonrandom cytogenetic picture exists and how this may be related to other
      associated tumor types.

PMID- 17011993
TI  - Gastric non-Hodgkin lymphoma in a trisomy X female.

PMID- 17011994
TI  - Acute myelogenous leukemia with monosomy 7 in a Hiroshima survivor 60 years after
      the atomic bomb.

PMID- 17011997
TI  - Management of aneurysms involving branches of the celiac and superior mesenteric
      arteries: a comparison of surgical and endovascular therapy.
AB  - OBJECTIVE: Aneurysms involving branches of the superior mesenteric and celiac
      arteries are uncommon and require proper management to prevent rupture and death.
      This study compares surgical and endovascular treatment of these aneurysms and
      analyzes outcome. METHODS: Patients at the Mount Sinai Medical Center in New York
      who were treated for aneurysms in the branches of the celiac artery and superior
      mesenteric artery were identified through a search of the institution's medical
      records and endovascular database. Patient demographics, history, clinical
      presentation, aneurysm characteristics, treatments, and follow-up outcome were
      retrospectively recorded. Significant differences between patients treated by
      surgical or endovascular therapy were determined by using Student's t test and
      chi2 analysis. RESULTS: Between January 1, 1991, and July 1, 2005, 59 patients
      with 61 aneurysms were treated at a single institution. Twenty-four patients had
      surgical repair, and 35 underwent endovascular treatment, which included coil
      embolization and stent-graft therapy. Splenic (28) and hepatic (22) artery
      aneurysms predominated. Eighty-nine percent of splenic artery aneurysms were true
      aneurysms and were treated by endovascular and surgical procedures in near equal
      numbers (14 and 11, respectively). Pseudoaneurysms were significantly more likely
      to be treated by endovascular means (P < .01). The technical success rate of
      endovascular treatment for aneurysms was 89%, and failures were successfully
      treated by repeat coil embolization in all patients who presented for
      retreatment. Patients treated by endovascular techniques had a significantly
      higher incidence of malignancy than patients treated with open surgical
      techniques (P = .03). Furthermore, patients treated by endovascular means had a
      shorter in-hospital length of stay (2.4 vs 6.6 days, P < .001). CONCLUSION:
      Endovascular management of visceral aneurysms is an effective means of treating
      aneurysms involving branches of the celiac and superior mesenteric arteries and
      is particularly useful in patients with comorbidities, including cancer. It is
      associated with a decreased length of stay in the elective setting, and failure
      of primary treatment can often be successfully managed percutaneously.

PMID- 17011998
TI  - Do device characteristics impact outcome in carotid artery stenting?
AB  - OBJECTIVES: The study was conducted to identify patient and procedural parameters
      that negatively impact the 30-day rates for stroke, death and transient ischemic
      attack (TIA) after carotid artery stenting (CAS) and that might be modified or
      further studied in future efforts to improve CAS. METHODS: This was a
      retrospective investigation of a dual-center CAS database of 701 consecutive CAS
      patients (414 men; mean age, 72.4 +/- 8.4). A subset of patient-related, lesion
      related, or procedure-related variables (age >or=80, left sided lesion,
      symptomatic, nicotine abuse, hypertension, diabetes mellitus, other peripheral
      vascular disease, hypercholesterolemia, embolic protection devices usage,
      predilation, ulcerated lesion, echolucent plaque, restenosis after surgery) were
      analyzed for association with occurrence of stroke, death, or TIA <or=30 days
      after CAS. The odds ratio (OR) and 95% confidence interval (CI) and P value were
      calculated for each variable to predict adverse outcome. RESULTS: The overall
      combined rate of stroke, death, and TIA within this database was 3.7% at 30 days.
      In the total population of 701 patients, only the OR of 2.7 for
      hypercholesterolemia (95% CI, 1.0 to 7.3; P = .041) was found to be significant.
      Subgroup analysis of the 304 symptomatic patients (43%) showed that open-cell
      stent designs and concentric EPD designs yielded an OR of 4.1 (95% CI, 1.4 to 12,
      P = .0136) and 3.3 (95% CI, 1.016 to 10, P = .0525), respectively, for 30-day
      stroke/death/TIA within this database. Analysis of open-cell stent designs and
      concentric EPD designs in patients with echolucent lesions yielded an OR of 3.1
      (95% CI,1.2 to 8.2, P = .0343) and 3.7 (95% CI, 1.3 to 10, P = .0174),
      respectively, for 30-day stroke/death/TIA. CONCLUSIONS: We conclude that
      increased analysis of device design variables may be necessary. Particularly in
      symptomatic patients or with echolucent lesions, closed-cell design and eccentric
      filters seem superior. Prospective investigation comparing open-cell vs closed
      cell stents and eccentric vs concentric filter devices may be warranted.

PMID- 17012000
TI  - Use of antibiotic-loaded polymethylmethacrylate beads for the treatment of
      extracavitary prosthetic vascular graft infections.
AB  - PURPOSE: This study was conducted to assess the efficacy of antibiotic-loaded
      polymethylmethacrylate (PMMA) beads in the management of lower extremity
      extracavitary prosthetic arterial graft infection. METHODS: This was a
      retrospective review of 34 patients treated for vascular surgical site (VSS)
      infections involving 36 prosthetic lower extremity arterial bypasses using
      antibiotic-loaded PMMA beads and culture-specific parenteral antibiotics for 4 to
      6 weeks. Sites of graft infection were explored, debrided, and cultured. As
      determined from the results of Gram's stains of VSS purulence, PMMA powder was
      polymerized with an antibiotic (vancomycin, daptomycin, or tobramycin/gentamicin,
      or a combination), molded into a chain of beads, and implanted adjacent to the
      infected graft after debridement and pulsed-spray antibacterial lavage. All
      wounds were closed primarily with planned exploration to verify sterilization
      before a graft preservation or in situ replacement procedure. Treatment outcomes,
      including wound sterilization, were analyzed based on tissue culture isolates,
      procedures for persistent infection, and freedom from graft infection. RESULTS:
      Cultures isolated 42 pathogens, (32 gram-positive, 9 gram-negative, 1 Candida
      albicans) with methicillin-resistant Staphylococcus aureus (MRSA) cultured from
      16 (44%) of 36 surgical site infections. As determined from the initial operative
      Gram's stain or a prior culture result, vancomycin PMMA beads were implanted in
      29 of 36 VSS infections at the first procedure; daptomycin (n = 4) or tobramycin
      (n = 3) beads were implanted in the rest. Repeat VSS exploration and culture
      results led to an average of 2.5 antibiotic bead replacements before definitive
      treatment. A sterile (no growth on tissue culture) VSS was achieved in 87% of
      cases before a graft preservation (n = 16) or in-situ replacement of an infected
      graft (n = 20) procedure. No patient deaths occurred. Early and late limb salvage
      was 100%. Infection recurred in 4 (11%) VSSs during a mean 23-month follow-up
      period, one within 3 months owing to unrecognized bowel injury associated with in
      situ replacement of an aortofemoral graft limb. CONCLUSION: Antibiotic-loaded
      PMMA beads may be a useful adjunct in the contemporary surgical management of VSS
      infection involving a prosthetic graft. Wound sterilization was achieved in most
      VSSs before graft preservation or an in-situ replacement procedure, including
      infections caused by MRSA, a pathogen isolated in half of the extracavitary
      prosthetic graft infections. This preliminary trial shows the potential benefit
      of this new technique, but further study is required to prove efficacy.

PMID- 17012001
TI  - Intermediate results of percutaneous endovascular therapy of femoropopliteal
      occlusive disease: a contemporary series.
AB  - BACKGROUND: Percutaneous endovascular therapy is becoming a primary option for
      managing infrainguinal occlusive disease. This study examined the results of
      femoropopliteal percutaneous transluminal angioplasty (PTA) with intermediate
      (mean, 24 months) follow-up in a contemporary series of patients presenting with
      critical limb ischemia or claudication. METHODS: Femoropopliteal PTA was
      performed on 238 consecutive limbs (208 patients) from January 2002 to July 2004.
      Study end points, including primary patency, assisted patency, and limb salvage
      (Society of Vascular Surgery reporting standards), were assessed by Kaplan-Meier
      life-table analysis, and factors predictive of hemodynamic or clinical failure,
      or both, were evaluated by univariate and multivariate methods. RESULTS: Clinical
      and demographic features included a mean age, 72 years; male (62%); critical limb
      ischemia (46%); diabetes mellitus (49%); and renal insufficiency (creatinine >or=
      1.5 mg/dL) (29%). Lesions were classified as TransAtlantic Inter-Society
      Consensus (TASC) A (11%), B (43%), C (41%), and D (5%). PTA was confined to the
      femoropopliteal segment in 77 patients (33%), and 161 (67%) underwent concurrent
      interventions in other anatomic locations. Femoropopliteal interventions included
      angioplasty only in 183 (78%), and the remaining 53 (22%) received at least one
      stent. Technical success was achieved in 97% of patients, with no deaths and a
      major morbidity rate of 3%. The 36-month actuarial primary patency was 54.3%, and
      assisted patency was 92.6% (37 peripheral reinterventions), resulting in a limb
      preservation rate of 95.4% in all patients regardless of clinical presentation.
      Interval conversion to bypass surgery occurred in 19 patients (8%). Comparison
      between critical limb ischemia and claudication revealed a primary patency of
      40.8% vs 64.8%, assisted patency of 93.8% vs 92.6%, and limb salvage of 89.7% vs
      100%, respectively. Negative predictors of primary patency determined by
      multivariate analysis included history of congestive heart failure (P = .02) and
      TASC C/D (P = .02). However, further evaluation of TASC C/D vs A/B revealed an
      assisted patency of 89.7% vs 94.3% (P = .37) and limb salvage of 94.3% vs 96.4%
      (P = .58). CONCLUSIONS: Femoropopliteal PTA can be performed with a low
      perioperative morbidity and mortality. Intermediate primary patency is directly
      related to TASC classification. Although secondary intervention is often
      necessary to maintain patency in TASC C/D lesions, these data suggest that it
      would be appropriate to use PTA as initial therapy for chronic femoropopliteal
      occlusive disease regardless of clinical classification at presentation or TASC
      category of lesion severity.

PMID- 17012002
TI  - Lack of relationship between gait parameters and physical function in peripheral
      arterial disease.
AB  - OBJECTIVE: Physical function is limited in patients with peripheral arterial
      disease who are symptomatic with intermittent claudication (PAD-IC). When
      patients with PAD-IC experience claudication, previous reports have described
      gait abnormalities, including alterations in step length and cadence. This study
      tested the hypothesis that patients with PAD-IC would have a decrease in usual
      and maximal walking speed and that this alteration in gait parameters would
      contribute to their decreased physical function scores, even in the absence of
      claudication. The aims were to evaluate usual and maximal walking speed and gait
      parameters (step length, cadence and toe out angle) in subjects with PAD-IC and
      control subjects with similar baseline activity levels. METHOD: A cross-sectional
      study of 25 subjects with PAD-IC compared with 26 age-matched controls was
      conducted in a research laboratory in an academic medical center. Study subjects
      were similar in age, gender, and physical activity status. Subjects with PAD-IC
      had an ankle-brachial index <0.90 in at least one leg and reported symptoms of
      intermittent claudication that limited walking ability. Subjects in either group
      were excluded if they used assistive devices to walk or were limited in walking
      ability by orthopedic, neurologic, cardiac, or pulmonary symptoms. Gait
      parameters were assessed at the onset of walking (before the development of
      claudication pain in the PAD-IC group) at self-selected and maximal walking
      speeds during which step and stride characteristics were collected. Subjects
      completed a physical activity recall, a Short Form questionnaire (SF-36), and a 6
      minute walk that was limited by claudication in the PAD-IC group. RESULTS: During
      gait testing, no patient with PAD-IC developed claudication. There were no
      significant differences between the PAD-IC and control groups in usual or maximal
      walking speed or other gait variables (step length, cadence, stride width, toe
      out angle). In contrast, the SF-36 physical function score was reduced 15.2
      percentage points (P < .02) and the summary physical component score was reduced
      6.7 percentage points in the PAD-IC group compared with controls (P = .002). In
      addition, the 6-minute walk distance was significantly less in the PAD-IC group
      than in the control group by 308.8 feet (P < .001). A series of bivariate
      analyses demonstrated that PAD-IC was the best predictor of reduced physical
      function, whereas no gait parameter was associated with reduced physical
      function. CONCLUSION: Patients with PAD-IC have significantly reduced 6-minute
      walk distance and reduced physical function by questionnaire scores that was not
      explained by any effects of PAD-IC on walking speed and selected gait parameters
      assessed before the onset of claudication pain.

PMID- 17012003
TI  - Comparison of new continuous measurements of ambulatory venous pressure (AVP)
      with conventional tiptoe exercise ambulatory AVP in relation to the CEAP clinical
      classification of chronic venous disease.
AB  - INTRODUCTION: Quantitative measurements of chronic venous insufficiency (CVI) are
      sensitive in detecting the presence of CVI but have low specificity in
      differentiating clinical severities of CVI as defined by the CEAP classification.
      One possible reason for this is measurement techniques do not assess variables
      that reflect hemodynamic changes that occur during normal exercise. Our aim was
      to compare the association of variables determined from a new technique,
      continuous ambulatory venous pressure monitoring (CAVPM), and those of
      conventional AVP measurement with the clinical severity of chronic venous
      insufficiency in patients with primary venous reflux. METHODS: Fifty-four limbs
      of 49 patients with CVI and 15 healthy controls were studied. CVI clinical
      severity was classified according to CEAP as C2&C3 (mild disease), C4 (moderate
      disease), and C5&C6 (severe disease). All participants underwent duplex
      ultrasound scanning to rule out the presence of reflux in the control group and
      to confirm it in the patient groups. Conventional AVP measurements, including 90%
      refilling time (RT90), were compared with the new CAVP variables of mean walking
      pressure (MWP) and percentage fall in walking pressure (%FWP). Data were analyzed
      by analysis of variance using the Kruskal-Wallis test, and comparisons between
      groups were performed using Mann-Whitney tests. Discriminant analysis was used to
      determine the ability of a test to classify limbs into clinical classes. RESULTS:
      Conventional AVP measurements could not differentiate between the control group
      and the presence of mild disease (P = .56) but did differentiate between controls
      and severe disease as well as mild and severe disease (P < .001). RT90 detected
      differences between controls and reflux groups (P < .001) but not between
      moderate (C4) and severe (C5&C6) clinical groups (P > .5). MWP and %FWP showed
      significant differences between all clinical severities and controls (P < .001).
      CONCLUSION: In the assessment of CVI, mean walking pressure and percent fall in
      walking pressure are more reliably associated with anatomic distribution of
      reflux and clinical severity of CVI than the gold standard investigations of
      conventional AVP and RT90.

PMID- 17012004
TI  - Prevention of recurrence of venous ulceration: randomized controlled trial of
      class 2 and class 3 elastic compression.
AB  - OBJECTIVE: To compare venous ulcer recurrence and compliance with two strengths
      of compression hosiery. METHODS: This study was a randomized controlled trial
      with a 5-year follow-up. The setting was the leg ulcer clinics of a teaching and
      a district general hospital in Scotland, United Kingdom. Patients were 300
      outpatients with recently healed venous ulcers, with no significant arterial
      disease, rheumatoid disease, or diabetes mellitus. Interventions were fitting and
      supply of class 2 or class 3 compression hosiery. Four-monthly refitting by
      trained orthotists and surveillance by specialist nurses were performed. The main
      outcome measures were recurrence of leg ulceration and compliance with treatment.
      RESULTS: Thirty-six percent (107/300) of patients had recurrent leg ulceration by
      5 years. Recurrence occurred in 59 (39%) of 151 class 2 elastic compression cases
      and in 48 (32%) of class 3 compression cases. One hundred six patients did not
      comply with their randomized compression class, 63 (42%) in class 3 and 43 (28%)
      in class 2. The difference in recurrence is not statistically significant, but
      our estimate of the effectiveness of class 3 hosiery is diluted by the lower
      compliance rate in this group. Restricted ankle movement and four or more
      previous ulcers were associated with a higher risk of recurrence. CONCLUSIONS:
      There was no evidence of a difference in recurrence rates at the classic level of
      significance (5%), but the lowest recurrence rates were seen in people who wore
      the highest degree of compression. Therefore, patients should wear the highest
      level of compression that is comfortable.

PMID- 17012005
TI  - Interface pressure and stiffness of ready made compression stockings: comparison
      of in vivo and in vitro measurements.
AB  - OBJECTIVE: It is unknown if the pressure values of compression stockings
      indicated by the producers correspond to the actual compression pressure exerted
      in vivo. This study compared pressure and stiffness of ready-made compression
      stockings (Venosan) of different classes, measured on the leg and by laboratory
      testing. METHODS: This was an experimental study conducted in a textile
      laboratory of a company that manufactures compression stockings. Twelve legs from
      healthy volunteers were fitted with ready-made calf-length compression stockings
      of the European classes I, II and III. In addition, two class I stockings were
      applied over each other. The in vivo interface pressure was measured using the
      medical stocking tester (MST) in position B1, eight cm proximal to the inner
      ankle. Stiffness was defined by an increase of pressure due to an increase of
      stretch that reflects the elastic property of the textile and was assessed by
      measuring the difference of interface pressure between standing and supine
      position at B1. In the laboratory, the MST was used to check the pressure of
      these stockings on wooden leg models. Then circular slices were cut out from the
      stockings at the B1 level and stretched by a Zwick dynamometer in the transverse
      direction. Force/extension-curves were plotted, from which the pressure and
      stiffness of each individual stocking was calculated. RESULTS: The pressure
      profile measured on four positions along the leg by MST showed a degressive
      gradient on the wooden model but not on the human leg due to the measuring
      geometry in the ankle region. Pressure values on the leg correspond to the in
      vitro measurements calculated from the force/extension-curve with a bias
      (difference of the means) of -2.1 and 4.1 mm Hg. In 95% of the subjects, the
      difference was between -10.1 and 5.8 mm Hg (Bland Altman plot). The correlation
      between in vivo and in vitro measurement was highly significant (P < .0001,
      Spearman correlation coefficient; r = .8161). In vivo and in vitro measurement
      shows an increase of stiffness with increasing compression classes. The highest
      values are found for two class I stockings applied over each other. CONCLUSION:
      Pressure and stiffness can be measured in vivo, correlate well with laboratory
      findings, and should be used in future studies, especially when different
      compression devices are to be compared.

PMID- 17012006
TI  - Combined saphenous ablation and iliac stent placement for complex severe chronic
      venous disease.
AB  - BACKGROUND: Severe chronic venous disease frequently has a complex
      pathophysiology. This study describes results after combined interventions to
      correct outflow obstruction and superficial reflux, even in the presence of deep
      venous reflux. METHODS: Between 1997 and 2005, 99 limbs in 96 patients had
      percutaneous iliofemoral venous stenting combined with great saphenous vein (GSV)
      stripping (39 limbs), or percutaneous GSV ablation performed by radiofrequency
      (27 limbs) or laser (33 limbs). Clinical severity score in CEAP was C4 in 51
      limbs, C5 in eight limbs, and C6 in 40 limbs; median age was 56 years (range, 27
      to 87 years); left-right limb ratio, 2.3:1; female-male ratio, 1.8:1; primary
      secondary etiology, 58:41. Perioperative investigations included visual analogue
      pain scale (VAS), degree of swelling (grade 0 to 3); quality-of-life
      questionnaire; venous filling index in milliliters per second (VFI90), venous
      filling time in seconds (VFT), percentage in ambulatory venous pressure drop
      (AVP), duplex Doppler scanning, and radiologic studies. RESULTS: Clinical follow
      up was performed in 97 (98%) of 99 for up to 5.5 years. Axial deep reflux was
      found in 27% (27/99). At least three venous segments were refluxing in 40% of
      limbs. Preoperative hemodynamic parameters reflected the presence of reflux and
      improved significantly (P < .01) after the procedure (VFI90, 3.8 to 2.3 mL/s;
      VFT, 11 to 16 seconds; AVP, 55% to 65%). No patients died, and the morbidity with
      endovenous GSV ablation was largely limited to ecchymosis and thrombophlebitis in
      the thigh area. Cumulative primary, assisted primary, and secondary stent patency
      rates at 4 years were 83%, 97%, and 97%, respectively. After treatment, limb
      swelling and pain substantially improved. The rate of limbs with severe pain
      (>or=5 on VAS) fell from 44% to 3% after intervention. Gross swelling (grade 3)
      decreased from 30% to 6% of limbs. Cumulative analysis showed sustained complete
      relief of pain (VAS = 0) and swelling (grade 0) after 4 years in 73% and 47% of
      limbs, respectively. Ulcers healed in 26 (68%) of 38 ulcerated limbs. Cumulative
      ulcer-healing rate was 64% at 48 months. All quality-of-life categories
      significantly improved after treatment. CONCLUSION: The single-stage combination
      of percutaneous venous stenting and superficial ablation in patients with severe
      chronic venous disease is safe, gives excellent symptom relief and improvement of
      quality of life, and a well-maintained ulcer-healing rate. It seems logical to
      initially perform multiple minimally invasive interventions rather than open
      surgery. Any associated deep reflux can initially be ignored pending clinical
      response to the combined intervention.

PMID- 17012007
TI  - Critical parameter of burst pressure measurement in development of bypass grafts
      is highly dependent on methodology used.
AB  - BACKGROUND: Because of the low patency rate of currently available vascular
      bypass grafts, researchers are working towards the development of alternative
      bypass grafts, ranging from synthetic prostheses to wholly biologic living
      grafts. The philosophy of measurement required by regulatory agencies such as the
      United States Food and Drug Administration (FDA) as well as to gain the
      Conformite Europeene (CE) mark is to test above and beyond the limits that would
      be expected physiologically. The critical parameter of burst pressure is needed
      for Conformite Europeene (CE) mark or United States Food and Drug Administration
      (FDA) approval before clinical trials can proceed. An accurate measurement of
      burst pressure in potential porous vascular bypass grafts is, therefore, of
      utmost importance to ensure adequate strength on implantation in animals and
      subsequent clinical use. A wide range of methods to measure burst pressure have
      been used. We tested the burst pressure of a new polyurethane-based nanocomposite
      vascular prosthesis by using different methods to assess whether the method used
      affected the results. METHODS: Water was infused at flow rates of 0.2, 50, and
      100 mL/min through a syringe pump into latex sleeve-lined porous prostheses
      manufactured from a poly(carbonate-urea)urethane nanocomposite incorporating
      silsesquioxane. At the lowest infusion rate, the inflation was done with and
      without a nonporous inner lining sleeve. A pressure transducer was used to record
      the peak pressure achieved. RESULTS: Using a nonporous sleeve resulted in a
      higher burst pressure (428 mm Hg vs 341 mm Hg) at a flow rate of 0.2 mL/min. A
      lower infusion rate (0.2 mL/min) produced a lower burst pressure than 50 mL/min
      (428 mm Hg vs 451 mm Hg). No significant difference was found in burst pressure
      using infusion rates of 50 mL/min and 100 mL/min. CONCLUSIONS: The use of a
      nonporous sleeve removes the potential weakness presented by the pores
      themselves. A continuous high infusion rate consistently overestimates burst
      pressure. These methods may not reflect the physiologic state. Care needs to be
      taken in interpretation of methodology for burst pressure measurement, and the
      rate of infusion should be stated in any description of the method. CLINICAL
      RELEVANCE: The poor patency of small-caliber vascular bypass prostheses has
      stimulated a large body of research into alternative graft materials. This
      includes synthetic and, more recently, tissue-engineered hybrid products.
      Acceptance for international standards requires demonstration of a rigorous
      mechanical testing regimen, including graft strength, which has on the whole
      involved burst strength measurement. However, the methods used to measure burst
      strength have varied with respect to apparatus used and rate of graft inflation.
      We show that these variables lead to markedly different results. In particular,
      fast infusion rates may overestimate the actual burst pressure, leading to a
      false sense of security.

PMID- 17012008
TI  - Ginkgolide A attenuates homocysteine-induced endothelial dysfunction in porcine
      coronary arteries.
AB  - BACKGROUND: Homocysteine is an independent risk factor for atherosclerosis. The
      objective of this study was to investigate whether ginkgolide A (GA), a major
      constituent of Ginkgo biloba, could block homocysteine-induced endothelial
      dysfunction in porcine coronary arteries. METHODS: Porcine coronary artery rings
      were assigned to six treatment groups: control; homocysteine (50 micromol/L); low
      dose (50 micromol/L) or high-dose (100 micromol/L) GA; and homocysteine plus low
      dose or high-dose GA. After 24 hours' incubation, the rings were analyzed for
      vasomotor function in response to a thromboxane A2 analogue (U46619), bradykinin,
      and sodium nitroprusside. Endothelial nitric oxide synthase (eNOS) was studied by
      using real-time polymerase chain reaction and immunohistochemistry analysis.
      Superoxide anion production was assessed by chemoluminescence analysis. RESULTS:
      Endothelium-dependent relaxation (bradykinin) was significantly reduced in ring
      segments treated with homocysteine as compared with the control (P < .05). When
      homocysteine was combined with either low-dose or high-dose GA, endothelium
      dependent relaxation was markedly recovered. There was no significant difference
      in maximal contraction (U46619) or endothelium-independent relaxation (sodium
      nitroprusside) among all groups. In addition, superoxide anion production was
      increased by 113% in the homocysteine-treated group, whereas there was no
      statistically significant difference between the control and GA/homocysteine
      groups. Furthermore, eNOS messenger RNA and protein levels were substantially
      reduced in the homocysteine-treated group (P < .05), but not in the
      GA/homocysteine combined groups. CONCLUSIONS: Homocysteine significantly impairs
      endothelium-dependent vasorelaxation through oxidative stress and downregulation
      of eNOS in porcine coronary arteries. GA effectively prevents homocysteine
      induced endothelial dysfunction and molecular changes in porcine coronary
      arteries. This study underscores the potential clinical benefits and applications
      of GA in controlling homocysteine-associated vascular injury and cardiovascular
      disease. CLINICAL RELEVANCE: Homocysteine is an independent risk factor for
      atherosclerosis. This study showed that ginkgolide A, a major constituent of
      Ginkgo biloba, effectively prevents homocysteine-induced endothelial dysfunction
      and molecular changes in porcine coronary arteries. This study underscores
      potential clinical benefits and applications of ginkgolide A in controlling
      homocysteine-associated vascular injury and cardiovascular disease.

PMID- 17012009
TI  - Gene expression changes evoked in a venous segment exposed to arterial flow.
AB  - OBJECTIVE: This study was conducted to characterize the coordinated molecular
      changes evoked in the structure and composition of the wall of a venous segment
      when exposed to fistula flow. METHODS: An arteriovenous shunt was created in
      adult C57BL/6J mice. Remodeled veins and contralateral control jugular veins were
      isolated 7 days after surgery. Total RNA was isolated, linearly amplified, and
      the transcriptional profiles of this early adaptive response were obtained by
      microarray analysis. Histologic and immunohistochemical analyses were performed
      on remodeled veins and control veins isolated on days 1, 3, 5, and 7 after
      surgery to further examine distinct spatial and temporal aspects of this early
      process. RESULTS: There were 131 significantly upregulated and 165 downregulated
      genes in the remodeled vein compared with the control jugular vein. Genes
      involved in extracellular matrix reorganization were highly upregulated. Movat's
      pentachrome staining revealed ground substance on day 3 that was not observed on
      day 5. The appearance of elastin fibers was first observed on day 7. Morphometric
      analysis demonstrated maximum wall thickness on day 3. Immunohistochemical
      analysis revealed the presence of tenascin-C, thrombospondin, lysyl oxidase, and
      osteopontin in different cell types at different time points throughout the first
      week after surgery. CONCLUSION: Major changes in the organization of the
      extracellular matrix occur during the early response of venous remodeling.
      Elastin, tenascin-C, thrombospondin, lysyl oxidase, and osteopontin are expressed
      within the wall of the remodeling vein resulting in the de novo formation of an
      extracellular matrix scaffold that may be part of a critical adaptation program
      being evoked to allow the vessel to cope with its new biomechanical environment.
      CLINICAL RELEVANCE: The Kidney Dialysis Outcomes Quality Initiative has proposed
      the construction of arteriovenous fistulas as the primary vascular access for
      hemodialysis. As the vein is exposed to arterial flow, the vein wall dilates and
      a vascular remodeling process is triggered. With continued exposure, intimal
      hyperplasia occurs at the anastomosis that in many cases leads to failure.
      However, the molecular mechanisms by which the outflow vein remodels into a
      mature fistula remain incompletely understood. By investigating venous remodeling
      in a fistula model, candidate genes important for the remodeling process are
      discovered and their functional significance examined. Thus, the identification
      of relevant genes involved in this process should provide insight into
      arteriovenous fistula maturation and may suggest novel approaches for achieving
      higher patency rates.

PMID- 17012010
TI  - Cystic adventitial disease of the femoral vein presenting as deep vein
      thrombosis: a case report and review of the literature.
AB  - Cystic adventitial disease of veins is a rare condition. We report the case of a
      28-year-old man who presented with a swollen leg secondary to obstruction of the
      common femoral vein as a result of this disease. He underwent excision of the
      cyst and made a full recovery. The presentation, investigation, treatment and
      pathology of this condition is discussed.

PMID- 17012011
TI  - Endovascular occlusion of right to left arteriovenous shunt associated with
      persistent left superior vena cava.
AB  - Left-sided superior vena cava (SVC) as the result of persistence of the left
      superior cardinal vein in postnatal life is a rare congenital anomaly, is usually
      associated with other cardiac defects, and can cause symptoms of right to left
      shunt. We report the case of a 58-year-old Asian man with a history of end-stage
      renal disease and Ebstein anomaly that was corrected surgically who presented
      with progressively worsening disabling dyspnea. An echocardiogram with
      concomitant intravenous saline injection raised the suspicion of right to left
      shunt, a finding that was confirmed with contrast injection of the left SVC that
      rapidly filled the left heart chambers and subsequently the aortic arch. To treat
      this anomaly, we accessed the left basilic vein under ultrasound guidance and
      inserted a 14F sheath into the left subclavian vein. A covered stent was then
      prepared at the back table with three Prolene 4-0 sutures that were wrapped
      around the middle portion of the graft to achieve a controlled area of stenosis
      after deployment. The stent graft was placed along the proximal innominate vein
      and the contiguous part of the left SVC. Coil embolization was then performed
      with coils that were positioned at the stenotic area of the covered stent. An
      immediate venogram demonstrated residual flow into the left SVC; however, a
      delayed venogram 2 weeks after the procedure showed occlusion of the left SVC and
      the development of collaterals to the right innominate vein that was draining to
      a normal right SVC. The patient remained marginally hypotensive after surgery,
      but he soon noted a substantial improvement in his symptoms. A repeat
      echocardiogram with intravenous saline injection confirmed the correction of the
      right to left shunt. Endovascular repair of persistent left SVC is feasible and
      safe and can be performed with minimal morbidity.

PMID- 17012012
TI  - Endovascular stenting of ascending lumbar veins for refractory inferior vena cava
      occlusion.
AB  - Chronic inferior vena cava (IVC) occlusion is a debilitating disease process.
      Recently, endovascular techniques have been described using progressive balloon
      dilatation and stenting to treat IVC occlusion with reasonable success. We
      present two cases of endovascular dilatation and stenting of the ascending lumbar
      vein. This technique provided good early relief of symptoms with ulcer healing,
      decreased swelling, and decreased pain. To our knowledge this is the first report
      of endovascular therapy of IVC occlusion via stenting of the ascending lumbar
      vein. This technique may provide a feasible treatment option when the occluded
      IVC cannot be reopened.

PMID- 17012013
TI  - Giant popliteal aneurysm presenting with foot drop.
AB  - Popliteal aneurysms are the most common peripheral arterial aneurysm and occur
      most commonly among older men with established cardiovascular disease. Popliteal
      aneurysms are asymptomatic or otherwise present with intermittent claudication,
      pressure symptoms in the popliteal fossa, distal embolization, and, rarely,
      rupture. We present a patient with a remarkably large popliteal aneurysm of 10 cm
      presenting as a popliteal swelling with foot drop and no signs of limb ischemia.
      According to our literature search, it is the largest reported popliteal
      aneurysm, and its corresponding symptoms are unusual. The diagnostic workup and
      treatment are presented.

PMID- 17012014
TI  - Unmasking complicated atherosclerotic plaques on carotid magnetic resonance
      angiography: a report of three cases.
AB  - In stenotic lesions of the extracranial carotid arteries, the presence of
      intraplaque hemorrhage or thrombosed ulceration is considered to pose an
      additional risk. Although contrast-enhanced magnetic resonance angiography (MRA)
      is a powerful means for looking at the vascular lumen, it provides little
      information on the vessel wall, particularly when mask subtraction methods are
      used. We report three cases in which the maximal intensity projections obtained
      from gadolinium-enhanced MRA source images showed only internal carotid artery
      stenoses, whereas source images revealed a focal increased T1 signal in the wall
      of the internal carotid artery, representing either intraplaque hemorrhage or
      thrombosed ulceration. Hence, the physicians interpreting an MRA in an acute
      stroke patient should not limit themselves to the synthetic maximal intensity
      projections but should also always review the source partitions, which can
      contain information related to an acute intraplaque accident.

PMID- 17012015
TI  - Bilateral obturator bypass for combined aortic and femorofemoral graft infection.

PMID- 17012016
TI  - Prevention of air travel-related deep venous thrombosis with mechanical devices:
      active foot movements produce similar hemodynamic effects.
AB  - OBJECTIVE: We compared the hemodynamic effects of different mechanical devices
      aimed for prevention of travel-related deep venous thrombosis with active foot
      movements. METHODS: Two battery-operated intermittent pneumatic compression (IPC)
      devices and three foot and calf muscle pump facilitating devices (PFD) that
      claimed to prevent travel-related deep venous thrombosis were tested in 17
      healthy volunteers on the ground and in 8 of same volunteers during flight. Flow
      changes during active foot movements were compared with the effects of each of
      the tested devices. RESULTS: There was no significant difference in hemodynamic
      effect between PFDs and active foot movements. The hemodynamic effects of IPC
      devices were significantly less compared with active foot movements. Values
      obtained during air flights were not significantly different from those obtained
      on the ground. CONCLUSIONS: Whereas IPC use for prevention of venous stasis
      during flight can be justified for immobile patients or during sleep, PFDs do not
      provide additional hemodynamic benefits compared with simple movements of the
      foot.

PMID- 17012017
TI  - Pay for performance: the process and its evolution.

PMID- 17012018
TI  - Ethics and professionalism: do we need yet another surgeons' charter?

PMID- 17012019
TI  - Regarding "Diffuse phlegmonous phlebitis after endovenous laser treatment of the
      great saphenous vein".

PMID- 17012020
TI  - Regarding "Replanting the inferior mesenteric artery during infrarenal aortic
      aneurysm repair: influence on postoperative colon ischemia".

PMID- 17012023
TI  - Protein palmitoylation.

PMID- 17012024
TI  - Assays of protein palmitoylation.
AB  - Protein palmitoylation plays an important role in the structure and function of a
      wide array of proteins. Unlike other lipid modifications, protein palmitoylation
      is highly dynamic and cycles of palmitoylation and depalmitoylation can regulate
      protein function and localization. The dynamic nature of palmitoylation is poorly
      resolved because of limitations in assay methods. Here, we discuss various
      methods that can be used to measure protein palmitoylation and identify sites of
      palmitoylation. We describe new methodology based on "fatty acyl exchange
      labeling" in which palmitate is removed via hydroxylamine-mediated cleavage of
      the palmitoyl-thioester bond and then exchanged with a sulfhydryl-specific
      labeling compound. The techniques are highly sensitive and allow for quantitative
      estimates of palmitoylation. Unlike other techniques used to assay
      posttranslational modifications, the techniques we have developed can label all
      sites of modification with a variety of probes, radiolabeled or non-radioactive,
      and can be used to assay the palmitoylation of proteins from tissue samples.

PMID- 17012026
TI  - Purification and characterization of recombinant protein acyltransferases.
AB  - Palmitoylation enhances membrane association and plays a role in the subcellular
      trafficking and signaling function of proteins. Unlike other forms of protein
      lipidation, such as prenylation and myristoylation, palmitoylation is reversible
      and can therefore play a regulatory role. Enzyme activities have recently been
      described in mammals and yeast that carry out the palmitoylation of protein
      substrates. Protein acyltransferases (PATs) transfer a palmitoyl moiety derived
      from palmitoyl-CoA to a free thiol of a substrate protein to create a labile
      thioester linkage. Biochemical characterization and kinetic analysis of this new
      family of enzymes requires methods to purify PATs and their substrates, as well
      as methods to assay PAT activity. We describe a series of methods using yeast and
      bacterial expression systems to study protein acyltransferases.

PMID- 17012025
TI  - Proteomic identification of palmitoylated proteins.
AB  - A proteomic method that purifies and identifies palmitoylated proteins from
      complex protein extracts is described. Using the fatty acid exchange labeling
      chemistry (described in the preceding report), palmitoyl modifications are
      exchanged for biotinylated compounds, allowing the subset of palmitoyl-proteins
      to be affinity-purified and then identified by mass spectroscopic protein
      identification technologies. The advantages and pitfalls of this new technology
      are discussed within the context of the recent application of this method in the
      yeast Saccharomyces cerevisiae.

PMID- 17012027
TI  - Synthesis of palmitoylated Ras-peptides and -proteins.
AB  - In this review, an overview is given and details are provided for the synthesis
      of lipidated Ras (rat-adeno-sarcoma)-peptides and -proteins. The progress made in
      the synthesis of the lipidated peptides from the Ras superfamily is discussed
      with special emphasis on the recently developed solid-phase synthesis methods,
      since these methods have turned out to be the preferred synthesis method for the
      majority of the required peptides. Solid-phase lipopeptide synthesis has given
      access to native and modified peptides on a scale that allows peptide-consuming
      studies like for ligation to proteins and concomitant X-ray crystal structure
      determination. The access to these peptides has also enabled biological questions
      concerning these peptides and proteins to be resolved. The review describes
      different solid-phase methods, which are individually suited for different types
      of lipopeptides, differing for example in lipidation pattern or amino acid side
      chain functionality, and their ligation to proteins. Finally, an example is
      provided how these peptides can serve to resolve biological aspects of the Ras
      family GTPases.

PMID- 17012028
TI  - In vitro and cellular assays for palmitoyl acyltransferases using fluorescent
      lipidated peptides.
AB  - Protein palmitoylation is emerging as an important post-translational
      modification in development as well as in the establishment and progression of
      diseases such as cancer. This chapter describes the use of fluorescent lipidated
      peptides to characterize palmitoyl acyltransferase (PAT) activities in vitro and
      in intact cells. The peptides mimic two motifs that are enzymatically
      palmitoylated, i.e. C-terminal farnesyl and N-terminal myristoyl sequences. These
      substrate peptides can be separated from the palmitoylated product peptides by
      reversed-phase HPLC, detected and quantified by the fluorescence of their NBD
      label. Through these methods, the activities of PATs toward these alternate
      substrates in isolated membranes or intact cells can be quantified. The in vitro
      assay has been used to characterize human PATs and to identify inhibitors of
      these enzymes. The cellular assay has been useful in elucidating the kinetics of
      protein palmitoylation by PATs in situ, and the sub-cellular distribution of the
      palmitoylated products.

PMID- 17012029
TI  - Probing protein palmitoylation at the yeast vacuole.
AB  - A protein's function depends on its localization to the right cellular
      compartment. A number of proteins require lipidation to associate with membranes.
      Protein palmitoylation is a reversible lipid modification and has been shown to
      mediate both membrane localization and control protein function. At the yeast
      vacuole, several palmitoylated proteins have been identified that are required
      for vacuole biogenesis, including the fusion factor Vac8, the SNARE Ykt6 and the
      casein kinase Yck3. Moreover, both the DHHC-CRD acyltransferase Pfa3 and Ykt6 are
      involved in palmitoylation at the vacuole Here, we present and discuss methods to
      probe for protein palmitoylation at vacuoles.

PMID- 17012030
TI  - Systematic screening for palmitoyl transferase activity of the DHHC protein
      family in mammalian cells.
AB  - Posttranslational modifications, including phosphorylation, ubiquitination and
      lipid modifications, provide proteins with additional functions and regulation
      beyond genomic information. Palmitoylation is a reversible lipid modification
      with palmitic acid that plays critical roles in protein trafficking and function.
      However, the enzymes that mediate palmitoyl acyl transferase (PAT) have been
      elusive. Recent genetic analysis in yeast revealed that members of cysteine-rich
      DHHC domain containing proteins (DHHC proteins) mediate palmitoylation. In
      mammalian genomes, 23 DHHC proteins are predicted raising the possibility of a
      large family of PAT enzymes. Here, we describe a systematic method to examine
      which of the DHHC family members is responsible for palmitoylation of a
      substrate.

PMID- 17012031
TI  - FRAP beam-size analysis to measure palmitoylation-dependent membrane association
      dynamics and microdomain partitioning of Ras proteins.
AB  - Motions of membrane-associated proteins within and between membranes are
      essential for many cellular functions. We describe the application of
      fluorescence recovery after photobleaching (FRAP) beam-size analysis to
      investigate the role of palmitoylation in the membrane targeting and membrane
      association dynamics of H-Ras. The method described distinguishes between FRAP by
      lateral diffusion and by cytoplasmic exchange, and enables to obtain an estimate
      of the membrane affinity in live cells. These studies show distinct roles for the
      two palmitoylation sites (Cys181 and Cys184) on H-Ras, with different effects on
      membrane affinity and microlocalization.

PMID- 17012032
TI  - Use of analogs and inhibitors to study the functional significance of protein
      palmitoylation.
AB  - Covalent attachment of palmitate to proteins is a post-translational modification
      that exerts diverse effects on protein localization and function. The three key
      technical approaches required for an investigator to determine the role of
      palmitoylation of your favorite palmitoylated protein (YFPP) are methods to: (1)
      detect YFPP palmitoylation; (2) alter or inhibit palmitoylation of YFPP; (3)
      determine the functional significance of altered YFPP palmitoylation. Here, I
      describe experimental methods to address these three issues. Both radioactive
      (radiolabeling with [(3)H]palmitate or (125)I-IC16 palmitate) and non-radioactive
      (chemical labeling and mass spectrometry) methods to detect palmitoylated
      proteins are presented. Next, techniques to inhibit protein palmitoylation are
      described. These include site specific mutagenesis, and treatment of cells with
      inhibitors of protein palmitoylation, including 2-bromopalmitate, cerulenin, and
      tunicamycin. Alternative methods to replace palmitate with other fatty acids are
      also presented. Finally, general approaches to determining the effect of altered
      palmitoylation status on YFPP association with membranes and lipid rafts, as well
      as signal transduction, are described.

PMID- 17012033
TI  - Fluorescence-based methods to image palmitoylated proteins.
AB  - A well known function of palmitoylation is to promote protein binding to cell
      membranes. Until recently, it was unclear what additional roles, if any,
      palmitoylation has in controlling protein localization in cells. Recent studies
      of palmitoylated forms of the small GTPase Ras have now revealed that
      palmitoylation plays multiple roles in the regulation of protein trafficking,
      including targeting proteins into the secretory pathway and recycling proteins
      between the plasma membrane and Golgi complex. We here describe how quantitative
      fluorescence microscopy and photobleaching approaches can be used to study the
      intracellular targeting and trafficking of GFP-tagged palmitoylated proteins in
      living cells. We discuss (1) general considerations for fluorescence recovery
      after photobleaching (FRAP) measurements of GFP-tagged proteins; (2) FRAP-based
      assays to test the strength of binding of palmitoylated proteins to cell
      membranes; (3) methods to establish the kinetics and mechanisms of recycling of
      palmitoylated proteins between the Golgi complex and the plasma membrane; (4) the
      use of the palmitoylation inhibitor 2-bromo-palmitate as a tool to study the
      dynamic regulation of protein targeting and trafficking by palmitate turnover.

PMID- 17012034
TI  - Reinvention.

PMID- 17012035
TI  - Keynote comment: Radiotherapy in the age of molecular oncology.

PMID- 17012036
TI  - High-dose chemotherapy in children with newly-diagnosed medulloblastoma.

PMID- 17012037
TI  - A better crystal ball to predict lung-cancer survival?

PMID- 17012038
TI  - Molecular imaging in diagnosis of neuroendocrine tumours.

PMID- 17012039
TI  - Risks and benefits of chloroquine use in anticancer strategies.

PMID- 17012040
TI  - Preimplantation genetic diagnosis for cancer.

PMID- 17012041
TI  - Is a radiotherapy boost truly beneficial?

PMID- 17012043
TI  - Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and
      stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude
      Medulloblastoma-96): long-term results from a prospective, multicentre trial.
AB  - BACKGROUND: Current treatment for medulloblastoma, which includes postoperative
      radiotherapy and 1 year of chemotherapy, does not cure many children with high
      risk disease. We aimed to investigate the effectiveness of risk-adapted
      radiotherapy followed by a shortened period of dose-intense chemotherapy in
      children with medulloblastoma. METHODS: After resection, patients were classified
      as having average-risk medulloblastoma (< or = 1.5 cm2 residual tumour and no
      metastatic disease) or high-risk medulloblastoma (> 1.5 cm2 residual disease or
      metastatic disease localised to neuraxis) medulloblastoma. All patients received
      risk-adapted craniospinal radiotherapy (23.4 Gy for average-risk disease and 36.0
      39.6 Gy for high-risk disease) followed by four cycles of cyclophosphamide-based,
      dose-intensive chemotherapy. Patients were assessed regularly for disease status
      and treatment side-effects. The primary endpoint was 5-year event-free survival;
      we also measured overall survival. This study is registered with
      ClinicalTrials.gov, number NCT00003211. FINDINGS: Of 134 children with
      medulloblastoma who underwent treatment (86 average-risk, 48 high-risk), 119
      (89%) completed the planned protocol. No treatment-related deaths occurred. 5
      year overall survival was 85% (95% CI 75-94) in patients in the average-risk
      group and 70% (54-84) in those in the high-risk group (p=0.04); 5-year event-free
      survival was 83% (73-93) and 70% (55-85), respectively (p=0.046). For the 116
      patients whose histology was reviewed centrally, histological subtype correlated
      with 5-year event-free survival (p=0.04): 84% (74-95) for classic histology, 77%
      (49-100) for desmoplastic tumours, and 57% (33-80) for large-cell anaplastic
      tumours. INTERPRETATION: Risk-adapted radiotherapy followed by a shortened
      schedule of dose-intensive chemotherapy can be used to improve the outcome of
      patients with high-risk medulloblastoma.

PMID- 17012044
TI  - Survival patterns after oophorectomy in premenopausal women: a population-based
      cohort study.
AB  - BACKGROUND: A statistical model of death due to ovarian cancer, breast cancer,
      coronary heart disease, hip fracture, and stroke has suggested that women who
      undergo prophylactic bilateral oophorectomy are at increased risk of death for
      all causes. We aimed to investigate survival patterns in a population-based
      sample of women who had received an oophorectomy and compare these with women who
      had not received an oophorectomy. METHODS: From an existing cohort of all women
      who underwent unilateral or bilateral oophorectomy while residing in Olmsted
      County, MN, USA, in 1950-87, we analysed those who had received an oophorectomy
      for a non-cancer indication before the onset of menopause. Every member of the
      cohort was matched by age to a referent woman in the same population who had not
      undergone oophorectomy. 1293 women with unilateral oophorectomy, 1097 with
      bilateral oophorectomy, and 2390 referent women were eligible for the study.
      Women were followed up until death or the end of the study (staggered over 2001
      06) by use of direct or proxy interviews, medical records in a records-linkage
      system, and death certificates. FINDINGS: Overall, mortality was not increased in
      women who underwent bilateral oophorectomy compared with referent women. However,
      mortality was significantly higher in women who had received prophylactic
      bilateral oophorectomy before the age of 45 years than in referent women (hazard
      ratio 1.67 [95% CI 1.16-2.40], p=0.006). This increased mortality was seen mainly
      in women who had not received oestrogen up to the age of 45 years. No increased
      mortality was recorded in women who underwent unilateral oophorectomy in either
      overall or stratified analyses. INTERPRETATION: Although prophylactic bilateral
      oophorectomy undertaken before age 45 years is associated with increased
      mortality, whether it is causal or merely a marker of underlying risk is
      uncertain.

PMID- 17012045
TI  - 4-year mortality in patients with non-small-cell lung cancer: development and
      validation of a prognostic index.
AB  - BACKGROUND: Lung cancer is the commonest cause of death due to cancer in the
      world. Non-small-cell lung carcinoma (NSCLC) represents about 80% of overall lung
      cancer cases worldwide. An accurate predictive model of mortality in patients
      with NSCLC could be useful to clinicians, policy makers, and researchers involved
      in risk stratification. The objective of this study was to develop and validate a
      simple prognostic index for 4-year mortality in patients with NSCLC by use of
      information obtained at the time of lung cancer diagnosis. METHODS: In 2000, 4669
      patients with histologically or cytologically proven NSCLC were enrolled
      prospectively from 137 pneumology departments in French general hospitals.
      Patients not lost to follow-up (n=4479) were randomly assigned to the development
      cohort (n=2979) or the validation cohort (n=1500). Every patient's physician
      completed a standard and anonymous questionnaire. We used a Cox model to identify
      variables independently associated with mortality and weighted the variables to
      create a prognostic index. FINDINGS: Median follow-up for survivors was 49 months
      (IQR 46-51). There were 2585 deaths (87%) in the development cohort and 1310
      deaths (87%) in the validation cohort. Five independent predictors of mortality
      were identified: age (>70 years, 1 point); sex (male, 1 point); performance
      status at diagnosis (reduced activity, 3 points; active >50%, 5 points; inactive
      >50%, 8 points; and total incapacity, 10 points); histological type (large-cell
      carcinoma, 2 points); and tumour-node-metastasis (TNM) staging system (IIA or
      IIB, 3 points; IIIA or IIIB, 6 points; and IV, 8 points). The minimum and maximum
      possible point scores were 0 and 22, respectively. Scores of the prognostic index
      were strongly associated with 4-year mortality in the development cohort: 0-1
      points predicted a 35% (95% CI 28-43) risk, 2-4 points a 59% (52-66) risk, 5-7
      points a 77% (72-81) risk, 8-10 points an 88% (85-90) risk, 11-14 points a 97%
      (96-98) risk, and 15-22 points a 99% (97-100) risk. The corresponding percentages
      in the validation cohort were 36% (24-47), 60% (50-70), 77% (71-83), 89% (86-93),
      96% (95-98), and 99% (98-100), respectively. The prognostic index showed good
      discrimination, with mean bootstrap c statistics of 0.85 (95% CI 0.84-0.86) in
      the development cohort and 0.86 (95% CI 0.85-0.87) in the validation cohort.
      INTERPRETATION: This prognostic index, incorporating personal, tumour, and
      functional information would be helpful in guiding patient management, resource
      use, and the design of clinical trials.

PMID- 17012046
TI  - Pelvic exenteration for gynaecological tumours: achievements and unanswered
      questions.
AB  - Pelvic exenteration has been used for 60 years to treat cancers of the lower and
      middle female genital tract in radiated pelves. The mainstay for treatment
      success in terms of locoregional control and long-term survival is resection of
      the pelvic tumour with clear margins (R0). New ablative techniques based on
      developmentally derived surgical anatomy and laterally extended endopelvic
      resection have raised the number of R0 resections done, even for tumours that
      extend to the pelvic side wall, which were traditionally judged a
      contraindication for exenteration. Although mortality has fallen to less than 5%,
      treatment-related severe morbidity of pelvic exenteration still exceeds 50%,
      possibly because of compromised healing of irradiated tissue and use of complex
      reconstructive techniques. The benefits of exenteration for patients who have
      advanced primary disease or recurrent tumours after surgery, versus those who
      have chemoradiotherapy, are not proven by results of controlled trials, but can
      be assumed from retrospective data. Comparative findings are missing, and
      arguments are unconvincing to favour pelvic exenteration over less extensive
      treatments and best supportive care for palliation of cancer symptoms in most
      patients.

PMID- 17012047
TI  - Image-guided radiotherapy: rationale, benefits, and limitations.
AB  - Technological advances have greatly enhanced the specialty of radiation oncology
      by allowing more healthy tissue to be spared for the same or better tumour
      coverage. Developments in medical imaging are integral to radiation oncology,
      both for design of treatment plans and to localise the target for precise
      administration of radiation. At planning, definition of the tumour and healthy
      tissue is based on CT, augmented frequently with MRI and PET. At treatment, three
      dimensional soft-tissue imaging can also be used to localise the target and
      tumour motion can be tracked with fluoroscopic imaging of radio-opaque markers
      implanted in or near the tumour. These developments allow changes in tumour
      position, size, and shape that take place during radiotherapy to be measured and
      accounted for to boost geometric accuracy and precision of radiation delivery.
      Image-guided treatment also enhances uniformity in doses administered in a
      population of patients, thus improving our ability to measure the effect of
      dosimetric and non-dosimetric factors on tumour and healthy tissue outcomes in
      clinical trials. Increased precision and accuracy of radiotherapy are expected to
      augment tumour control, reduce incidence and severity of toxic effects after
      radiotherapy, and facilitate development of more efficient shorter schedules than
      currently available.

PMID- 17012048
TI  - Clinical role of proton magnetic resonance spectroscopy in oncology: brain,
      breast, and prostate cancer.
AB  - Standardised proton magnetic resonance spectroscopic imaging (MRSI) was initially
      developed for routine in-situ clinical assessment of human brain tumours, and its
      use was later extended for examination of prostate and breast cancers. MRSI
      coupled with both routine and functional MRI techniques provides more detailed
      information about a tumour's location and extent of its infiltration than any
      other modality alone. Information obtained by adding MRSI data to anatomical and
      functional MRI findings aid in clinical management decisions (such as watchful
      waiting vs immediate intervention). In this Review, we discuss the current status
      of proton MRSI, with emphasis on its clinical use to map the location and extent
      of tumour processes for spectroscopic image-guided biopsy procedures and to
      monitor treatment paradigms for brain, prostate, and breast cancer.

PMID- 17012049
TI  - Neoadjuvant treatment for early-stage breast cancer: opportunities to assess
      tumour response.
AB  - Primary, preoperative, or neoadjuvant chemotherapy was introduced in the early
      1970s as part of an integrated therapeutic approach to treat inoperable locally
      advanced breast cancer. The approach resulted in high responses, and sufficient
      downstaging to allow mastectomy in some patients. In addition, a small number of
      pathological complete responders were reported. Gradually, the idea of
      preoperative chemotherapy was extended to include patients with large but
      operable early-stage breast cancer, with the possibility in some cases of
      downstaging the primary tumour to avoid mastectomy, and to allow breast
      conserving surgery to be done. This approach allows the tumour to be used as a
      measure of treatment response in vivo. More recently, the possibility has opened
      up for neoadjuvant chemotherapy to provide information on the use of clinical,
      pathological, and molecular endpoints, which can be used as surrogate markers to
      predict long-term outcome in the adjuvant setting. In addition, the anatomical
      accessibility of the breast provides the potential for serial biopsies to
      investigate molecular changes during treatment.

PMID- 17012050
TI  - Sirolimus monotherapy for Kaposi's sarcoma in an HIV-negative patient.

PMID- 17012052
TI  - Phyllodes breast tumour showing invasive squamous-cell carcinoma with invasive
      ductal, clear-cell, secretory, and squamous components.

PMID- 17012053
TI  - Changing the name of the journal.

PMID- 17012051
TI  - Cell differentiation and iodine-131 uptake in poorly differentiated thyroid
      tumour in response to nevirapine.

PMID- 17012054
TI  - Translational issues in neurorehabilitation.

PMID- 17012055
TI  - Plasticity.
AB  - Over the past 20 years, evidence has mounted regarding the capacity of the
      central nervous system to alter its structure and function throughout life.
      Injury to the central nervous system appears to be a particularly potent trigger
      for plastic mechanisms to be elicited. Following focal injury, widespread
      neurophysiological and neuroanatomical changes occur both in the peri-infarct
      region, as well as throughout the ipsi- and contralesional cortex, in a complex,
      time-dependent cascade. Since such post-injury plasticity can be both adaptive or
      maladaptive, current research is directed at understanding how plasticity may be
      modulated to develop more effective therapeutic interventions for neurological
      disorders, such as stroke. Behavioral training appears to be a significant
      contributor to adaptive plasticity after injury, providing a neuroscientific
      foundation for the development of physical therapeutic approaches. Adjuvant
      therapies, such as pharmacological agents and exogenous electrical stimulation,
      may provide a more receptive environment through which behavioral therapies may
      be imparted. This chapter reviews some of the recent results from animal models
      of injury and recovery that depict the complex time course of plasticity
      following cortical injury and implications for neurorehabilitation.

PMID- 17012056
TI  - Activity-based therapies.
AB  - Therapeutic activity is a mainstay of clinical neurorehabilitation, but is
      typically unstructured and directed at compensation rather than restoration of
      central nervous system function. Newer activity-based therapies (ABTs) are in
      early stages of development and testing. The ABTs attempt to restore function via
      standardized therapeutic activity based on principles of experimental psychology,
      exercise physiology, and neuroscience. Three of the best developed ABTs are
      constraint-induced therapy, robotic therapy directed at the hemiplegic arm, and
      treadmill training techniques aimed at improving gait in persons with stroke and
      spinal cord injury. These treatments appear effective in improving arm function
      and gait, but they have not yet been clearly demonstrated to be more effective
      than equal amounts of traditional techniques. Resistance training is clearly
      demonstrated to improve strength in persons with stroke and brain injury, and
      most studies show that it does not increase hypertonia. Clinical trials of ABTs
      face several methodological challenges. These challenges include defining dosage,
      standardizing treatment parameters across subjects and within treatment sessions,
      and determining what constitutes clinically significant treatment effects. The
      long-term goal is to develop prescriptive ABT, where specific activities are
      proven to treat specific motor system disorders. Activity-based therapies are not
      a cure, but are likely to play an important role in future treatment cocktails
      for stroke and spinal cord injury.

PMID- 17012057
TI  - Exercise rehabilitation after stroke.
AB  - Stroke is a leading cause of disability that results not only in persistent
      neurological deficits, but also profound physical deconditioning that propagates
      disability and worsens cardiovascular risk. The potential for exercise-mediated
      adaptations to improve function, fitness, and cardiovascular health after stroke
      has been underestimated: it represents an emerging arena in neurotherapeutics. To
      define the health rationale for cardiovascular (aerobic) exercise, we first
      outline the impact of debilitating secondary biological changes in muscle and
      body composition on fitness and metabolic health after stroke. We provide an
      overview of evidence-based advances in exercise therapeutics, with a focus on
      task-oriented models that combine a progressive aerobic conditioning stimulus
      with motor learning to improve multiple physiological domains that determine
      longitudinal outcomes after stroke. Although progress in development of safe and
      effective exercise strategies is advancing, fundamental questions regarding dose
      intensity, prescription to optimize central and peripheral neuromuscular
      adaptations, and the public health value of exercise in secondary stroke
      prevention remain unanswered. Key issues steering future research in exercise
      neurotherapeutics are discussed within the context of initiatives to facilitate
      translation to community-based studies, requisite for dissemination.

PMID- 17012058
TI  - Neurotransmitters and motor activity: effects on functional recovery after brain
      injury.
AB  - There are complex relationships among behavioral experience, brain morphology,
      and functional recovery of an animal before and after brain injury. A large
      series of experimental studies have shown that exogenous manipulation of central
      neurotransmitter levels can directly affect plastic changes in the brain and can
      modulate the effects of experience and training. These complex relationships
      provide a formidable challenge for studies aimed at understanding
      neurotransmitter effects on the recovery process. Experiments delineating
      norepinephrine-modulated locomotor recovery after injury to the cerebral cortex
      illustrate the close relationships among neurotransmitter levels, brain
      plasticity, and behavioral recovery. Understanding the neurobiological processes
      underlying recovery, and how they might be manipulated, may lead to novel
      strategies for improving recovery from stroke-related gait impairment in humans.

PMID- 17012059
TI  - Growth factors and stroke.
AB  - Current options for the treatment of stroke are extremely limited, partly because
      of the rapidity with which brain cells die when deprived of their blood supply.
      Several recent studies suggest that growth factors can produce improvement in
      animal models of stroke, even when administered at postischemic intervals of many
      hours to days, when conventional neuroprotective approaches are typically futile.
      Several growth factors can access the brain after systemic administration, making
      them more attractive as therapeutic agents. Finally, growth factors are key
      mediators of neurogenesis in the adult brain, which could have a role in brain
      repair and functional recovery following stroke.

PMID- 17012060
TI  - Neurorestorative treatment of stroke: cell and pharmacological approaches.
AB  - There is a compelling need to develop cell and pharmacological therapeutic
      approaches to be administered beyond the hyperacute phase of stroke. These
      therapies capitalize on the capacity of the brain for neuroregeneration and
      neuroplasticity and are designed to reduce neurological deficits after stroke.
      This review provides an update of bone marrow-derived mesenchymal stem cells
      (MSCs) and select pharmacological agents in clinical use for other indications
      that promote the recovery process in the subacute and chronic phases after
      stroke. Among these agents are 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitors (statins), erythropoietin (EPO), and phosphodiesterase type 5 (PDE-5)
      inhibitors and nitric oxide (NO) donors. Both the MSCs and the pharmacologic
      agents potentiate brain plasticity and neurobehavioral recovery after stroke.